PMID- 7860475 TI - Understanding the mechanisms of adverse drug reactions. PMID- 7860476 TI - Red cell membrane disorders. PMID- 7860477 TI - Isolated haematuria: an investigatory approach. PMID- 7860478 TI - Doctor patient relationship and a new syndrome--'Amedicus'. PMID- 7860479 TI - Peritoneal fibrosis--an expression of atenolol toxicity. PMID- 7860480 TI - Chemotherapy induced refractory anaemia with ring sideroblasts in carcinoma breast. PMID- 7860481 TI - Secretory immunoblastic lymphoma. PMID- 7860482 TI - "Gastropericardial fistula" presenting as cardiac tamponade. PMID- 7860483 TI - Cyclophosphamide-induced cardiomyopathy during bone marrow transplantation for severe aplastic anemia. PMID- 7860484 TI - Multivalvular thickening in a case of Hunter's syndrome. PMID- 7860485 TI - An unusual presentation of progressive systemic sclerosis. PMID- 7860486 TI - Recurrent bacterial meningitis. PMID- 7860487 TI - Devic's disease. PMID- 7860488 TI - Fibrous dysplasia of rib. PMID- 7860489 TI - Encysted ascites caused by entamoeba histolytica. PMID- 7860490 TI - Anaemia in kala-azar--a preliminary report. PMID- 7860491 TI - Surgical management of NIDDM. PMID- 7860492 TI - Role of insulin in non-cardiac pulmonary oedema in scorpion stings. PMID- 7860493 TI - Serum angiotensin converting enzyme in various medical disorders. PMID- 7860494 TI - Magnesium in cardiovascular therapy. PMID- 7860495 TI - Incidence of NIDDM in rural central bihar. PMID- 7860496 TI - Post streptococcal glomerulonephritis coexisting with acute rheumatic fever. PMID- 7860497 TI - Epidemiology of hypertension. PMID- 7860498 TI - The prevalence of hypertension in rural population around Sevagram. PMID- 7860499 TI - Multi organ failure. PMID- 7860500 TI - Familial multiple (asymmetrical) lipomatosis associated with small intestinal leiomyoma. PMID- 7860501 TI - Pregnancy and rheumatic diseases. PMID- 7860502 TI - Never forget malaria. PMID- 7860503 TI - Rheumatology--present status and future directions. PMID- 7860504 TI - Magnesium in aluminium phosphide poisoning--where have we erred? PMID- 7860505 TI - Hirudin: long live the leech! PMID- 7860506 TI - Assessing presence and degree of osteoporosis. PMID- 7860507 TI - Absolute lymphocytopenia as a diagnostic aid in bronchogenic carcinoma. AB - Total lymphocyte count and lymphocyte percentage were calculated in a group of 26 patients of Bronchogenic carcinoma and compared with the values in 22 cases of pulmonary tuberculosis. Patients of Bronchogenic carcinoma had a significant lymphocytopenia as compared to patients of tuberculosis. It is inferred that this peripheral lymphocytopenia can be used as a possible diagnostic pointer in patients of Bronchogenic carcinoma. PMID- 7860508 TI - Effect of D-penicillamine on lymphocyte subsets: correlation with clinical response in rheumatoid arthritis. AB - We studied the effects of D-penicillamine (DP) on the clinical response, immunoinflammatory parameters and the lymphocyte subsets in 46 patients with rheumatoid arthritis (RA). Patients were evaluated before the start of the drug and then at 3 and 9 months during the follow up. 38 of 46 (82.6%) patients could continue DP treatment for over 9 months, while in 8 the drug was withdrawn due to adverse effects. Improvement in the various disease activity indices of more than 50% (responders) was seen in 25 of 38 (65.8%) patients. Responders showed a significant decrease in the serum IgA and IgM at 9 months, and in IgM only at 3 months. The serum levels of C3 and C4 did not show any significant change. Serum levels of C-reactive protein and rheumatoid factor (RF) showed a significant decrease at 3 and 9 months. A significant decrease in CD3+ and CD4+ lymphocytes along with a fall in CD4+/CD8+ lymphocyte ratio was also seen in responders at 3 and 9 months, compared to the baseline. Our results suggest that DP may have immunomodulatory action in RA. PMID- 7860509 TI - Botulinum toxin A in blepharospasm and hemifacial spasm. AB - We report the first Indian experience of botulinum toxin A in the treatment of blepharospasm and hemifacial spasm. Sixteen patients, 7 with essential blepharospasm, 5 with Meige syndrome and 4 with hemifacial spasm received botulinum toxin A injection. One patient received 3 courses of injections, 2 received 2 courses and the rest received only one course. The effect was observed after a latent period of less than 48 hours in all patients and lasted for a mean of 16.65 weeks. More than 70% improvement occurred after 17/20 injections (85%). Poor response was more often seen when blepharospasm was associated with oromandibular dystonia (2/5 injections). Though the duration of response and subjective score of improvement was best in patients with hemifacial spasm, the numbers were very small for any statistical evaluation. The side effects were local, transient, mild and well tolerated. The commonest side effect was blepharoptosis. PMID- 7860511 TI - An epidemiological study of obesity in adults in the urban population of Delhi. AB - The prevalence of obesity and its associations were assessed during a community based epidemiological survey of coronary heart disease on a randomised sample of 13,414 adults in the age group 25-64 years living in urban Delhi. Body Mass Index (BMI) > 25 was considered to be the cut off point for defining obesity. By this criterion, the overall prevalence rate of obesity was 27.8%. Obesity was found to be more common in female subjects (Male--21.3%, Female--33.4%, p < 0.001). Obesity was more frequent in male subjects with lower physical activity compared to those doing heavier physical activity (29.3 vs 17.5%, p < 0.001). Physical activity did not influence the prevalence of obesity in females. Hypertension (24.8 vs 8.2%, p < 0.001) coronary heart disease (5.3 vs 2.4%, p < 0.001) and diabetes mellitus (3.2 vs 1.6%, p < 0.001) were more common in the obese than in the non-obese subjects. Hypercholesterolaemia (65.5 vs 53%, p < 0.001) and hypertriglyceridaemia (73.3 vs 61.1%, p < 0.001) were found to be associated with obesity. PMID- 7860510 TI - Evaluation of osteoporosis in patients with fracture neck of femur using conventional radiography. AB - Osteoporosis was assessed at the hip (Singh's index) and calcaneus (calcaneal index) using conventional radiography in 80 patients (31 men, 49 women) with fracture neck of femur. Forty four patients had intracapsular fracture neck of femur (ICFN), and 36 extracapsular fracture neck of femur (ECFN). Fractures occurred more with increasing age in both groups, with female preponderance in the older age group. Osteoporosis was more severe as age advanced. Singh's index decreased from 5.2 to 3 (ICFN), and from 4.1 to 2.65 (ECFN) with age. Calcaneal index decreased from 4.4 to 2.9 (ICFN) and from 4.1 to 2.6 (ECFN) with age. In summary degree of osteoporosis, assessed at the hip and calcaneus, increased with increasing age. Other recent studies have shown that calcaneal bone density is a valid method to predict future risk of hip fracture. PMID- 7860512 TI - Left ventricular function in end stage renal disease--non-invasive assessment in patients on maintenance hemodialysis. AB - Non-invasive assessment of left ventricular function was performed by echocardiography and radionuclide ventriculography in 17 end-stage renal disease patients on maintenance hemodialysis. Patients with diabetes mellitus, ischemic heart disease and pericardial or valvular heart disease were excluded from the study. Parameters studied on echocardiography were left ventricular internal diameter in diastole (LVIDd), left atrial diameter (LAD), Aortic root diameter (ARD), Left ventricular posterior wall thickness in systole (LVPWs), End diastolic volume (EDV), End Systolic volume (ESV), fractional shortening percentage (FS%) and ejection fraction (EF). Parameters studied on radionuclide ventriculography were Peak ejection rate (PER), Peak filling rate (PFR) and Ejection fraction (EF). Significantly abnormal values for echocardiographic parameters LVIDd, LVPWs, EDV, ESV and FS% were found. On evaluation by MUGA scans, it was observed that the PER was significantly decreased while the PFR and EF did not change significantly. PMID- 7860514 TI - New drugs from medicinal plants: opportunities and approaches. PMID- 7860513 TI - Incidence of intracavitary thrombus in dilated cardiomyopathy. AB - Study was made on 90 patients (63 males & 27 females) with Idiopathic dilated cardiomyopathy (DCM) to find out incidence of intracavitary thrombus in heart. None of the patient was found to have evidence of thrombus in any chamber of the heart during Echocardiography. Only one patient (1.1%) had developed arterial embolization. The mean age of the patients was 49.5 (+/- 16.31) years. The duration of illness was 2.82 (+/- 1.58) years. In view of above observation life long anticoagulation which has its own hazards & difficulties, does not seem to be advisable in all cases of DCM. PMID- 7860515 TI - Glucose-6-phosphate dehydrogenase deficiency in India and its clinical significance. PMID- 7860516 TI - Gastro-oesophageal reflux disease pathophysiology, diagnosis and management. PMID- 7860517 TI - Hirudins--new antithrombotic agent. PMID- 7860518 TI - Hypereosinophilic syndrome: the spectrum of clinical, haematological and morphological features. PMID- 7860519 TI - Malignant thymoma with cerebral metastases in association with pure red cell aplasia. PMID- 7860520 TI - Myotonia dystrophica with hereditary motor and sensory neuropathy. PMID- 7860521 TI - Critical illness polyneuropathy in a case of acute renal failure and sepsis. PMID- 7860522 TI - Wilson's disease: unusual clinical and radiological features. PMID- 7860523 TI - Hyperkalemia induced muscle paralysis in a patient of acute on chronic renal failure. PMID- 7860524 TI - Atypical case of testicular tumour. PMID- 7860525 TI - Vincristine induced thrombocytosis. PMID- 7860526 TI - Hereditary spherocytosis and glucose-6 phosphate dehydrogenase deficiency. PMID- 7860527 TI - Hypokalemic paralysis. PMID- 7860528 TI - Hypokalaemic periodic paralysis associated with thyrotoxicosis. PMID- 7860529 TI - Multiple myeloma presenting as acute paraplegia. PMID- 7860530 TI - Resistant Salmonella meningitis treated with oflaxacin--a quinolone compound. PMID- 7860531 TI - Reversible hemiplegia in a known diabetic with hypertension with renal failure. PMID- 7860532 TI - Potassium primed ECG test. PMID- 7860533 TI - Incidence of HIV infection in resistant cases of Indian kala-azar. PMID- 7860534 TI - Nasogastric quinine in severe malaria. PMID- 7860535 TI - Herpes simplex encephalitis in HIV-1 infection and AIDS in India. PMID- 7860536 TI - Proliferation of medical associations. PMID- 7860537 TI - Adverse drug reaction monitoring in India. PMID- 7860538 TI - Chylous ascites in carcinoma of breast. PMID- 7860539 TI - International Study of Asthma and Allergies in Childhood (ISAAC) PMID- 7860540 TI - Spontaneously resolving ring enhancing cerebral CT scan lesion. PMID- 7860541 TI - Is radioisotope liver scan investigation obsolete? PMID- 7860542 TI - Terminalia arjuna in cardiovascular therapy. PMID- 7860543 TI - 99m Tc DTPA scan as a diagnostic marker of acute rejection in renal transplantation. AB - Forty renal transplant recipients were subjected to 99m Technicium Diethylene triamine pentacetic acid (DTPA)scans at regular intervals & whenever there was suspection of rejection. Serial scans of a group of 15 recipients from immediate post transplant period till withdrawal of cyclosporine were analysed separately & the results compared to with single scan analysis. The sensitivity & specificity of DTPA scan in the absence of acute tubular necrosis (ATN) was 94.1% & 87.5%, while the positive & negative predictive values were 88.8 & 93.3% respectively. Sensitivity & specificity of serial scan analysis (88.8% and 75%) in early post transplant period was higher than that of interpretation of single scan (75% & 66%). Serial scan changes predated clinical rejection during cyclosporine withdrawal period. We conclude that DTPA scan is both a sensitive & specific non invasive diagnostic marker of acute rejection in absence of ATN & serial scans during early post transplant period & at the time of cyclosporine withdrawal are helpful in detecting the rejection accurately & at the earliest. PMID- 7860544 TI - Holter monitoring in chronic renal failure before & during dialysis. AB - Holter monitoring was done prospectively in 50 adult patients of chronic renal failure (CRF) before and during haemodialysis. Frequent premature ventricular contractions (PVC's) were present in 3 (6%), all during dialysis (Gp I). Sporadic PVC's were seen in 6 (12%) and rest 41 (82%) had no PVC (Gp II). Premature atrial contractions (PAC's) were frequent in 5 (10%) (one had precipitation during dialysis), sporadic in 7 (14%) and none in 38 (76%). Ventricular tachycardia (VT) was not seen. Supraventricular tachycardia (SVT) was observed in 5. No biochemical parameter correlated with arrhythmias. There was no correlation between hypotension episodes and arrhythmias. Sinus tachycardia occurred during the third and fourth hours of dialysis. This correlated with hypotensive episodes observed in 13 patients. Episodes of silent myocardial ischaemia (SMI) observed in 12 patients occurred predominantly during this period of tachycardia. Cardiac arrhythmias are infrequent in CRF and are mainly seen in patients with preexisting coronary artery disease with low ejection fractions (EF) (EF 0.37 +/- 0.2 in Gp I and 0.80 +/- 0.1 in Gp II P < 0.01) and abnormal Q waves in baseline ECG. They do not seem to contribute to occurrence of episodes of dialysis induced hypotension. PMID- 7860545 TI - Platelet functions and lipid profile in haemorrhagic and thrombotic stroke patients. AB - The present study was conducted in 17 patients of haemorrhagic stroke (HS), 19 patients of thrombotic stroke (TS) and 14 control subjects. In each subject platelet functions (spontaneous platelet aggregation (SPA), aggregation induced with 10, 5, 2.5 microM ADP and 10 micrograms/ml of collagen) and complete lipid profile (total cholesterol, triglycerides, high density lipoprotein [HDL], low density lipoprotein [LDL], very low density lipoprotein [VLDL] and LDL/HDL ratio) were performed within 7 days of onset of stroke. Platelet aggregation with 2.5 microM ADP was significantly lower (P < 0.05), in both the stroke groups in comparison to controls. No other changes were significant. Mean serum triglycerides and VLDL of TS group were significantly higher than that of controls. Mean LDL/HDL ratio of the same group was significantly lower than HS group. It can be concluded that alterations in platelet functions and lipid profile are induced by both types of strokes in acute stage. PMID- 7860546 TI - Noninvasive estimation of pulmonary artery wedge pressure by dual-M-mode echocardiography. AB - Pulmonary artery wedge pressure (PAWP) measurement is invasive, associated with complications, contraindications and its high cost limits its use in clinical practice. We evaluated the use of dual-M-mode-echocardiography as a possible noninvasive alternative method in 20 patients for estimating the PAWP. The interval from the Q-wave of the electrocardiogram (ECG) to the mitral valve closure on the mitral valve M-mode-echocardiogram (Q-MVC), the interval between the aortic valve closure and mitral valve E point (AVC-E) on aortic and mitral valve M-mode-ECG respectively and the ratio of these intervals (Q-MVC/AVC-E) was correlated to the mean PAWP measured at catheterization. The mean PAWP correlated excellently with Q-MVC/AVC-E ratio [r = 0.89, p < 0.0001, y = 14.51 (Q-MVC/AVC-E) + 6.71]. The estimation of PAWP by a dual-M-mode-ECG offers a useful estimate of mean PAWP noninvasively. PMID- 7860547 TI - Eighth nerve involvement in meningo-encephalitis. AB - Seventy-two patients suffering from meningo-encephalitis were studied, clinically, biochemically, microbiologically and virologically. Evidence of rising titre in serum and CSF of antibodies to Japanese encephalitis were present in 50% of cases, and recent past infection in 20% of cases. Cranial nerve involvement particularly the "8th" was present in 70% of cases though there was a 2.5% involvement of the 2nd, 3rd and 6th nerves. All the patients belonged to plain Tribal population and all had a history of eating pork 7-10 days prior to development of the infection. PMID- 7860548 TI - Comparison of Siriraj and Guy's Hospital score to differentiate supratentorial ischaemic and haemorrhagic strokes in the Indian population. AB - In India, 70% of the population does not have access to computerised brain scanning. Siriraj score is a safe and reliable clinical method to asses acute stroke syndrome. 160 patients with acute stroke were analysed by Siriraj and Guy's hospital stroke score simultaneously. CT Scan was performed in all and subarachnoid haemorrhage was excluded. Ninety two patients (57.5%) had infarction and 68 (42.5%) had haemorrhage. Siriraj score formula revealed haemorrhage in 53 (80%) and infarction in 78 (83%), while in the rest the results were equivocal or incorrect. Guy's hospital score revealed haemorrhage in 45 (66%) and infarction in 59 (69%). Clinical features are also helpful in differentiating infarction from haemorrhage, but the accuracy is not as high as with Siriraj score and secondly Siriraj score is a very simple formula in comparison to Guy's score. PMID- 7860549 TI - Incidence of Nelson's syndrome and residual adrenocortical function in patients of Cushing's disease after bilateral adrenalectomy. AB - Eighteen patients of Cushing's Disease, who had undergone bilateral "total" adrenalectomy 2 to 10 years back, were evaluated for residual adrenocortical function and for any evidence of Nelson's Syndrome. Surprisingly, all patients were discovered to have measurable plasma cortisol, albeit in the subnormal range. The standard criteria for accepting "completeness of adrenalectomy" were fulfilled in 16 patients. It was possible to wean one patient off replacement therapy. Thus, the dose of replacement steroids needs to be regulated according to the blood steroid levels in order to avoid unnecessary hypercortisolism. Radiological evidence of pituitary tumor diagnosed Nelson's Syndrome in 2 patients. Nelson's Syndrome was further suspected in 8 others who showed pigmentation. One of these had an enlarged sella and an erosion of the dorsum sellae, but had a normal CT scan. Another patient had evidence of incidental pituitary pathology (incidentaloma) which resolved spontaneously. Contrast enhanced CT scans of the sella are necessary for early detection of Nelson's Syndrome. PMID- 7860550 TI - Drug-induced cardiovascular disorders. PMID- 7860551 TI - Neurological manifestations of AIDS. PMID- 7860552 TI - AIDS--prevention always when there is no cure. PMID- 7860553 TI - Effect of music on the human brain alpha rhythm. PMID- 7860554 TI - Aneurysm of the inferior vena cava in association with dilated cardiomyopathy. PMID- 7860555 TI - Generalised seizure following sublingual buprenorphine. PMID- 7860556 TI - Traumatic right hemidiaphragmatic gastric hernia. PMID- 7860557 TI - IgG multiple myeloma and alloalbuminemia: as unusual association. PMID- 7860558 TI - Acute polyarthritis complicating chickenpox. PMID- 7860559 TI - Intra cranial cavernous haemangioma. PMID- 7860560 TI - Simplified emergency procedure for treatment of tension pneumothorax. PMID- 7860561 TI - Holiday heart syndrome. PMID- 7860562 TI - Acute renal failure and 9th, 10th nerve palsy in patient of kala-azar treated with stibanate. PMID- 7860563 TI - Maternal ECG changes with intrauterine fetal death. PMID- 7860564 TI - Churg Strauss syndrome. PMID- 7860566 TI - CT diagnosis of intracranial tuberculoma. PMID- 7860565 TI - Surgical management of NIDDM. PMID- 7860567 TI - Intracranial tuberculomata diagnosed by computed tomography. PMID- 7860568 TI - Smokeless tobacco--a challenging smoke. PMID- 7860569 TI - Steven Johnson syndrome following a single dose of ciprofloxacin. PMID- 7860570 TI - Dopamine infusion--poor alternative as stress test. PMID- 7860571 TI - Cephalosporins. PMID- 7860572 TI - Assessment of intravenous streptokinase therapy in acute myocardial infarction. PMID- 7860573 TI - Serodiagnostic evaluation of amoebic hepatitis. PMID- 7860574 TI - Patterns of rheumatic disease in 11931 Indian patients. PMID- 7860575 TI - Adverse effects of quinolone antibiotics. PMID- 7860576 TI - Quality of life in drug-resistant tuberculosis. PMID- 7860577 TI - Look into your cholesterol. PMID- 7860578 TI - "LGB syndrome: is albumino-cytological dissociation essential for the diagnosis". PMID- 7860579 TI - Are antitubercular drugs prescribed correctly and scientifically? PMID- 7860580 TI - Haemolytic jaundice in Plasmodium vivax infection. PMID- 7860581 TI - ompH gene expression is regulated by multiple environmental cues in addition to high pressure in the deep-sea bacterium Photobacterium species strain SS9. AB - Photobacterium species strain SS9 is a moderately barophilic (pressure-loving) deep-sea bacterial species which induces the expression of the ompH gene in response to elevated pressure. Here we demonstrate that at 1 atm (1 atm = 1.01325 x 10(5) Pa), ompH expression increases with cell density in 2216 marine medium batch culture and is subject to catabolite repression and the OmpH synthesis is inducible by energy (carbon) starvation. Regulatory mutants which are impaired in ompH gene expression at high pressure are also impaired in cell density regulation of ompH gene expression, indicating that the two inducing conditions overlap in their signal transduction pathways. The same promoter was activated by high cell density at 1 atm of pressure as well as during low-cell-density growth at 272 atm. Catabolite repression of ompH gene expression was induced by a variety of carbon sources, and this repression could be partially reversed in most cases by the addition of cyclic AMP (cAMP). Surprisingly, glucose repression of ompH transcription occurred only at 1 atm, not at 272 atm, despite the fact that catabolite repression was operational in SS9 under both conditions. It is suggested that ompH expression is cAMP and catabolite repressor protein dependent at 1 atm but becomes cAMP and perhaps catabolite repressor protein independent at 272 atm. Possible mechanisms of ompH gene activation are discussed. PMID- 7860582 TI - Proton pumping and the internal pH of yeast cells, measured with pyranine introduced by electroporation. AB - The internal pH of yeast cells was determined by measuring the fluorescence changes of pyranine (8-hydroxy-1,3,6-pyrene-trisulfonic acid), which was introduced into the cells by electroporation. This may be a suitable procedure for the following reasons. (i) Only minor changes in the physiological status of the cells seemed to be produced. (ii) The dye did not seem to leak at a significant rate from the cells. (iii) Different incubation conditions produced large fluorescence changes in the dye, which in general agree with present knowledge of the proton movements of the yeast cell under different conditions. (iv) Pyranine introduced by electroporation seemed to be located in the cytoplasm and to avoid the vacuole, and therefore it probably measured actual cytoplasmic pH. (v) Correction factors to obtain a more precise estimation of the internal pH are not difficult to apply, and the procedure may be useful for other yeasts and microorganisms, as well as for the introduction of other substances into cells. Values for the cytoplasmic pHs of yeast cells that were higher than those reported previously were obtained, probably because this fluorescent indicator did not seem to penetrate into the cell vacuole. PMID- 7860583 TI - Regulation of the molybdate transport operon, modABCD, of Escherichia coli in response to molybdate availability. AB - The mod (chlD) locus at 17 min on the Escherichia coli chromosome encodes a high affinity molybdate uptake system. To further investigate the structure and regulation of these genes, the DNA region upstream of the previously identified modBC (chlJD) genes was cloned and sequenced. A single open reading frame, designated modA, was identified and appears to encode a periplasmic binding protein for the molybdate uptake system. To determine how the mod genes are regulated in response to molybdate, nitrate, and oxygen, we constructed a series of mod-lacZ operon fusions to the upstream region and introduced them in single copy onto the E. coli chromosome. Whereas molybdate limitation resulted in elevated mod-lacZ expression, neither oxygen nor nitrate had any significant effect on gene expression. A regulatory motif, CATAA, located at the modA promoter was identified and shown to be required for molybdate-dependent control of the modABCD operon. Mutations within this sequence resulted in nearly complete derepression of gene expression and suggest that transcription of the operon is mediated by a molybdenum-responsive regulatory protein. PMID- 7860584 TI - Detection and quantification of Vibrio fischeri autoinducer from symbiotic squid light organs. AB - Vibrio fischeri is the specific light organ symbiont of the sepiolid squid species Euprymna scolopes and Euprymna morsei. Both species of squid are luminescent by virtue of their bacterial symbionts, but the natural symbionts of E. scolopes do not produce visible luminescence in laboratory culture. The primary cause of this depressed luminescence by E. scolopes symbionts in culture was found to be the production of relatively low levels of V. fischeri autoinducer, a positive transcriptional coregulator of the lux regulon, identified as N-(3-oxohexanoyl) homoserine lactone. Concentrations of autoinducer activity produced by these symbionts in culture were quantified and found to be at least 10-fold lower than those produced by E. morsei isolates (which are visibly luminous outside the association) and perhaps 10,000-fold lower than those of the brightest V. fischeri strains. Despite the differences in their symbiont strains, the intact light organs of the two species of squid contained comparable amounts of extractable autoinducer activity (between 100 and 200 pg per adult animal). The chromatographic behavior of this autoinducer activity on reverse-phase high-performance liquid chromatography was consistent with its presumptive identification as V. fischeri autoinducer. Within the 5-microliter volume of the epithelial core of the light organ in which the symbiotic V. fischeri strains are housed, these amounts would result in an effective autoinducer concentration of at least 100 nM. Because these levels are over 40 fold higher than the concentration needed for the induction of luminescence of bacteria in culture, we conclude that the inherent degree of autoinducer production by strains of V. fischeri may not influence their effectiveness as light organ symbionts. Furthermore, this study provides the first direct evidence that the phenomenon of cell density-dependent autoinduction, discovered and described first for laboratory cultures of V. fischeri but believed to be a general phenomenon in many species of host-associated symbionts and pathogens, is in fact a consequence of bacterial colonizations of host tissues. PMID- 7860585 TI - Genes required for cellulose synthesis in Agrobacterium tumefaciens. AB - A region of the chromosome of Agrobacterium tumefaciens 11 kb long containing two operons required for cellulose synthesis and a part of a gene homologous to the fixR gene of Bradyrhizobium japonicum has been sequenced. One of the cellulose synthesis operons contained a gene (celA) homologous to the cellulose synthase (bscA) gene of Acetobacter xylinum. The same operon also contained a gene (celC) homologous to endoglucanase genes from A. xylinum, Cellulomonas uda, and Erwinia chrysanthemi. The middle gene of this operon (celB) and both the genes of the other operon required for cellulose synthesis (celDE) showed no significant homology to genes contained in the databases. Transposon insertions showed that at least the last gene of each of these operons (celC and celE) was required for cellulose synthesis in A. tumefaciens. PMID- 7860586 TI - Mechanism of cellulose synthesis in Agrobacterium tumefaciens. AB - Extracts of Agrobacterium tumefaciens incorporated UDP-[14C]glucose into cellulose. When the extracts were fractionated into membrane and soluble components, neither fraction was able to synthesize cellulose. A combination of the membrane and soluble fractions restored the activity found in the original extracts. Extracts of cellulose-minus mutants showed no significant incorporation of UDP-glucose into cellulose. When mixtures of the extracts were made, the mutants were found to fall into two groups: extracts of mutants from the first group could be combined with extracts of the second group to obtain cellulose synthesis. No synthesis was observed when extracts of mutants from the same group were mixed. The groups of mutants corresponded to the two operons identified in sequencing the cel genes (A. G. Matthysse, S. White, and R. Lightfoot. J. Bacteriol. 177:1069-1075, 1995). Extracts of mutants were fractionated into membrane and soluble components, and the fractions were mixed and assayed for the ability to synthesize cellulose. When the membrane fraction from mutants in the celDE operon was combined with the soluble fraction from mutants in the celABC operon, incorporation of UDP-glucose into cellulose was observed. In order to determine whether lipid-linked intermediates were involved in cellulose synthesis, permeablized cells were examined for the incorporation of UDP [14C]glucose into material extractable with organic solvents. No radioactivity was found in the chloroform-methanol extract of mutants in the celDE operon, but radioactive material was recovered in the chloroform-methanol extract of mutants in the celABC operon. The saccharide component of these compounds was released after mild acid hydrolysis and was found to be mainly glucose for the celA insertion mutant and a mixture of cellobiose, cellotriose, and cellotetrose for the celB and celC insertion mutants. The radioactive compound extracted with chloroform-methanol form the celC insertion mutant was incorporated into cellulose by membrane preparations from celE mutants, which suggests that this compound is a lipid-linked intermediate in cellulose synthesis. PMID- 7860587 TI - Sporulation protein SpoIVFB from Bacillus subtilis enhances processing of the sigma factor precursor Pro-sigma K in the absence of other sporulation gene products. AB - Processing of inactive pro-sigma K to active sigma K in the mother cell compartment of sporulating Bacillus subtilis is governed by a signal transduction pathway emanating from the forespore and involving SpoIVFB in the mother cell. Coexpression of spoIVFB and sigK (encoding pro-sigma K) genes in growing B. subtilis or Escherichia coli enhanced pro-sigma K processing in the absence of other sporulation-specific gene products. The simplest explanation of these results is that SpoIVFB is a protease that processes pro-sigma K. PMID- 7860588 TI - Isolation and characterization of plasmid mutations that enable partitioning of pSC101 replicons lacking the partition (par) locus. AB - Second-site mutations that allow stable inheritance of partition-defective pSC101 plasmids mapped to seven distinct sites in the 5' half of the plasmid repA gene. While the mutations also elevated pSC101 copy number, there was no correlation between copy number increase and plasmid stability. Combinations of mutations enabled pSC101 DNA replication in the absence of integration host factor and also stabilized par-deleted plasmids in cells deficient in DNA gyrase or defective in DnaA binding. Our findings suggest that repA mutations compensate for par deletion by enabling the origin region RepA-DNA-DnaA complex to form under suboptimal conditions. They also provide evidence that this complex has a role in partitioning that is separate from its known ability to promote plasmid DNA replication. PMID- 7860589 TI - Flagellar filament structure and cell motility of Salmonella typhimurium mutants lacking part of the outer domain of flagellin. AB - We have isolated spontaneous mutants of Salmonella typhimurium which can swim in the presence of antifilament antibodies. The molecular masses of flagellins isolated from these mutants were smaller than that (52 kDa) of wild-type flagellin. Two mutants which produced the smallest flagellins (42 and 41 kDa) were selected, and the domain structures of the flagellins were analyzed by trypsin digestion and then subjected to amino acid sequencing. The two flagellins have deletions at Ala-204 to Lys-292 and Thr-183 to Lys-279, respectively. These deleted parts belong to the outer domain (D3) of flagellin, which is believed to be at the surface of the filament. These mutant filaments aggregated side by side in the presence of salt, resulting in disordered motility. PMID- 7860590 TI - Thermoregulation of virB transcription in Shigella flexneri by sensing of changes in local DNA superhelicity. AB - Transcription of the virB gene, a transcriptional regulator of invasion genes on the large plasmid of Shigella flexneri, is strictly regulated by growth temperature; when bacteria are grown at 37 degrees C, virB transcription is highly activated, while at 30 degrees C the level of virB transcription decreases to less than 5% of that at 37 degrees C. Transcription from the virB promoter is activated by VirF, which is encoded on the same plasmid, in a DNA superhelicity dependent manner (T. Tobe, M. Yoshikawa, T. Mizuno, and C. Sasakawa, J. Bacteriol. 175:6142-6149, 1993). Here we provide evidence supporting the involvement of negative superhelicity in the thermoregulation of virB transcription. A local negatively supercoiled domain in the virB promoter region was created by activating a divergent transcription from the T7 RNA polymerase dependent promoter, phi 10, which was placed upstream of the virB promoter in the opposite orientation. Transcription from the virB promoter was activated even at 30 degrees C by induction of divergent transcription. Levels of virB transcription correlated with levels of expressed T7 RNA polymerase. Transcriptional activation of virB by the system depended completely upon VirF function. The level of virB transcription achieved by introducing a negatively supercoiled domain was enough to give rise to expression of invasion capacity at 30 degrees C. These results indicated that the repression of virB transcription at 30 degrees C was caused by a reduction in negative superhelicity around the virB promoter region at 30 degrees C. PMID- 7860591 TI - Tracking the evolution of the bacterial choline-binding domain: molecular characterization of the Clostridium acetobutylicum NCIB 8052 cspA gene. AB - The major secreted protein of Clostridium acetobutylicum NCIB 8052, a choline containing strain, is CspA (clostridial secreted protein). It appears to be a 115,000-M(r) glycoprotein that specifically recognizes the choline residues of the cell wall. Polyclonal antibodies raised against CspA detected the presence of the protein in the cell envelope and in the culture medium. The soluble CspA protein has been purified, and an oligonucleotide probe, prepared from the determined N-terminal sequence, has been used to clone the cspA gene which encodes a protein with 590 amino acids and an M(r) of 63,740. According to the predicted amino acid sequence, CspA is synthesized with an N-terminal segment of 26 amino acids characteristic of prokaryotic signal peptides. Expression of the cspA gene in Escherichia coli led to the production of a major anti-CspA-labeled protein of 80,000 Da which was purified by affinity chromatography on DEAE cellulose. A comparison of CspA with other proteins in the EMBL database revealed that the C-terminal half of CspA is homologous to the choline-binding domains of the major pneumococcal autolysin (LytA amidase), the pneumococcal antigen PspA, and other cell wall-lytic enzymes of pneumococcal phages. This region, which is constructed of four repeating motifs, also displays a high similarity with the glucan-binding domains of several streptococcal glycosyltransferases and the toxins of Clostridium difficile. PMID- 7860593 TI - Identification of alcaligin as the siderophore produced by Bordetella pertussis and B. bronchiseptica. AB - The siderophores produced by iron-starved Bordetella pertussis and B. bronchiseptica were purified and were found to be identical. Using mass spectrometry and proton nuclear magnetic resonance, we determined that the siderophore produced by these organisms was identical to alcaligin, a siderophore produced by Alcaligenes denitrificans. PMID- 7860592 TI - Identification and isolation of a gene required for nitrate assimilation and anaerobic growth of Bacillus subtilis. AB - The Bacillus subtilis narA locus was shown to include narQ and narA. The putative product of narQ is similar to FdhD, which is required for formate dehydrogenase activity in Escherichia coli. NarA showed homology to MoaA, a protein involved in biosynthesis of the molybdenum cofactor for nitrate reductase and formate dehydrogenase. Analysis of mutants showed that narA but not narQ is required for both nitrate assimilation and respiration. PMID- 7860594 TI - A test of the directed mutation hypothesis in Escherichia coli MCS2 using replica plating. AB - Excision of phage Mu from Escherichia coli MCS2 was originally put forth as a clear example of directed mutation. This claim was considerably weakened, however, by subsequent evidence that Mu excision occurs during starvation regardless of fitness consequences. Here, I use the classical replica-plating technique to examine Mu excision during starvation of MCS2. The results support the conclusion that Mu excision is not directed but is, instead, nonspecifically induced by starvation. PMID- 7860595 TI - Pheromone-inducible conjugation in Enterococcus faecalis: interbacterial and host parasite chemical communication. PMID- 7860596 TI - Kinetic limitation and cellular amount of pyridoxine (pyridoxamine) 5'-phosphate oxidase of Escherichia coli K-12. AB - We report the purification and enzymological characterization of Escherichia coli K-12 pyridoxine (pyridoxamine) 5'-phosphate (PNP/PMP) oxidase, which is a key committed enzyme in the biosynthesis of the essential coenzyme pyridoxal 5' phosphate (PLP). The enzyme encoded by pdxH was overexpressed and purified to electrophoretic homogeneity by four steps of column chromatography. The purified PdxH enzyme is a thermally stable 51-kDa homodimer containing one molecule of flavin mononucleotide (FMN). In the presence of molecular oxygen, the PdxH enzyme uses PNP or PMP as a substrate (Km = 2 and 105 microM and kcat = 0.76 and 1.72 s 1 for PNP and PMP, respectively) and produces hydrogen peroxide. Thus, under aerobic conditions, the PdxH enzyme acts as a classical monofunctional flavoprotein oxidase with an extremely low kcat turnover number. Comparison of kcat/Km values suggests that PNP rather than PMP is the in vivo substrate of E. coli PdxH oxidase. In contrast, the eukaryotic enzyme has similar kcat/Km values for PNP and PMP and seems to act as a scavenger. E. coli PNP/PMP oxidase activities were competitively inhibited by the pathway end product, PLP, and by the analog, 4-deoxy-PNP, with Ki values of 8 and 105 microM, respectively. Immunoinhibition studies suggested that the catalytic domain of the enzyme may be composed of discontinuous residues on the polypeptide sequence. Two independent quantitation methods showed that PNP/PMP oxidase was present in about 700 to 1,200 dimer enzyme molecules per cell in E. coli growing exponentially in minimal medium plus glucose at 37 degrees C. Thus, E. coli PNP/PMP oxidase is an example of a relatively abundant, but catalytically sluggish, enzyme committed to PLP coenzyme biosynthesis. PMID- 7860597 TI - The octopine-type Ti plasmid pTiA6 of Agrobacterium tumefaciens contains a gene homologous to the chromosomal virulence gene acvB. AB - Although the majority of genes required for the transfer of T-DNA from Agrobacterium tumefaciens to plant nuclei are located on the Ti plasmid, some chromosomal genes, including the recently described acvB gene, are also required. We show that AcvB shows 50% identity with the product of an open reading frame, designated virJ, that is found between the virA and virB genes in the octopine type Ti plasmid pTiA6. This reading frame is not found in the nopaline-type Ti plasmid pTiC58. acvB is required for tumorigenesis by a strain carrying a nopaline-type Ti plasmid, and virJ complements this nontumorigenic phenotype, indicating that the products of these genes have similar functions. A virJ-phoA fusion expressed enzymatically active alkaline phosphatase, indicating that VirJ is at least partially exported. virJ is induced in a VirA/VirG-dependent fashion by the vir gene inducer acetosyringone. Primer extension analysis and subcloning of the virJ-phoA fusion indicate that the acetosyringone-inducible promoter lies directly upstream of the virJ structural gene. Although the roles of the two homologous genes in tumorigenesis remain to be elucidated, strains lacking acvB and virJ (i) are proficient for induction of the vir regulon, (ii) are able to transfer their Ti plasmids by conjugation, and (iii) are resistant to plant wound extracts. Finally, mutations in these genes cannot be complemented extracellularly. PMID- 7860598 TI - The gene for a major exopolyphosphatase of Saccharomyces cerevisiae. AB - The gene encoding a major exopolyphosphatase (scPPX1) in Saccharomyces cerevisiae (H. Wurst and A. Kornberg, J. Biol. Chem. 269:10996-11001, 1994) has been isolated from a genomic library. The gene, located at 57 kbp from the end of the right arm of chromosome VIII, encodes a protein of 396 amino acids. Overexpression in Escherichia coli allowed the ready purification of a recombinant form of the enzyme. Disruption of the gene did not affect the growth rate of S. cerevisiae. Lysates from the mutants displayed considerably lower exopolyphosphatase activity than the wild type. The enzyme is located in the cytosol, whereas the vast accumulation of polyphosphate (polyP) of the yeast is in the vacuole. Disruption of PPX1 in strains with and without deficiencies in vacuolar proteases allowed the identification of exopolyphosphatase activity in the vacuole. This residual activity was strongly reduced in the absence of vacuolar proteases, indicating a dependence on proteolytic activation. A 50-fold lower protease-independent activity could be distinguished from this protease dependent activity by different patterns of expression during growth and activation by arginine. With regard to the levels of polyP in various mutants, those deficient in vacuolar ATPase retain less than 1% of the cellular polyP, a loss that is not offset by additional mutations that eliminate the cytosolic exopolyphosphatase and the vacuolar polyphosphatases dependent on vacuolar protease processing. PMID- 7860599 TI - Digital image analysis of growth and starvation responses of a surface-colonizing Acinetobacter sp. AB - Surface growth of an Acinetobacter sp. cultivated under several nutrient regimens was examined by using continuous-flow slide culture, phase-contrast microscopy, scanning confocal laser microscopy, and computer image analysis. Irrigation of attached coccoid stationary-phase Acinetobacter sp. cells with high-nutrient medium resulted in a transition from coccoid to bacillar morphology. Digital image analysis revealed that this transition was biphasic. During phase I, both the length and the width of cells increased. In contrast, cell width remained constant during phase II, while both cell length and cell area increased at a rate greater than in phase I. Cells were capable of growth and division without morphological transition when irrigated with a low-nutrient medium. Rod-shaped cells reverted to cocci by reduction-division when irrigated with starvation medium. This resulted in conservation of cell area (biomass) with an increase in cell number. In addition, the changes in cell morphology were accompanied by changes in the stability of cell attachment. During phase I, coccoid cells remained firmly attached. Following transition in high-nutrient medium, bacillar cells displayed detachment, transient attachment, and drifting behaviors, resulting in a spreading colonization pattern. In contrast, cells irrigated with a low-nutrient medium remained firmly attached to the surface and eventually formed tightly packed microcolonies. It is hypothesized that the coccoid and bacillar Acinetobacter sp. morphotypes and associated behavior represent specialized physiological adaptations for attachment and colonization in low nutrient systems (coccoid morphotype) or dispersion under high-nutrient conditions (bacillar morphotype). PMID- 7860600 TI - An endo-N-acetyl-beta-D-glucosaminidase, acting on the di-N-acetylchitobiosyl part of N-linked glycans, is secreted during sporulation of Myxococcus xanthus. AB - After the demonstration that Stigmatella aurantiaca DW4 secretes an endo-N-acetyl beta-D-glucosaminidase (ENGase), acting on the di-N-acetylchitobiosyl part of N linked glycans (S. Bourgerie, Y. Karamanos, T. Grard, and R. Julien, J. Bacteriol. 176:6170-6174, 1994), an ENGase activity having the same substrate specificity was also found to be secreted during vegetative growth of Myxococcus xanthus DK1622. The activity decreased in mutants known to secrete less protein than the wild type (Exc +/-). During submerged development, the activity was produced in two steps: the first increase occurred during the aggregation phase, and the second one occurred much later, during spore formation. This production was lower in developmental mutants impairing cell-cell signaling, the late mutants (csg and dsg) being the most deficient. Finally, when sporulation was obtained either by starvation in liquid shake flask culture or by glycerol induction, the activity was produced exclusively by the wild-type cells during the maturation of the coat. PMID- 7860601 TI - Purification and initial characterization of the ATP:corrinoid adenosyltransferase encoded by the cobA gene of Salmonella typhimurium. AB - The cobA gene of Salmonella typhimurium and its product were overexpressed to approximately 20% of the total cell protein. CobA was purified to 98% homogeneity; N-terminal sequence analysis (21 residues) of homogeneous protein confirmed the predicted amino acid sequence. ATP:corrinoid adenosyltransferase activity was demonstrated in vitro to be associated with CobA. This activity was optimal at pH 8 and 37 degrees C. A quantitative preference was determined for Mn(II) cations and ATP. The apparent Km of CobA for ATP was 2.8 microM, and that for cob(I)alamin was 5.2 microM. Vmax was measured at 0.43 nmol/min. Cobinamide served as the substrate for CobA to yield adenosylcobinamide. Activity was stable at 4 degrees C for several weeks but was lost rapidly at room temperature (50% overnight). Dithiothreitol was required to maintain the enzymatic activity of CobA. PMID- 7860602 TI - Activation of the dephosphorylation of nitrogen regulator I-phosphate of Escherichia coli. AB - The transcription of sigma 54 RNA polymerase-dependent nitrogen-regulated genes is activated by nitrogen regulator I (NRI)-phosphate. The kinase NRII is responsible for the phosphorylation of NRI. It has been shown that NRII also has the ability to dephosphorylate NRI-phosphate but only when PII is present at a concentration greatly in excess of that of NRII. We have now shown that glutamate enables PII to stimulate the dephosphorylation of NRI-phosphate when present in equimolar concentration with NRII. This effect of glutamate appears to be a backup control that becomes effective when the normal regulation of PII activity is disabled. PMID- 7860603 TI - Cloning, expression, and characterization of the lon gene of Erwinia amylovora: evidence for a heat shock response. AB - The gene encoding the Lon protease of Erwinia amylovora has been cloned by complementation of an Escherichia coli lon mutant. Analysis of the determined nucleotide sequence of the lon gene revealed extensive homology to the nucleotide sequences of cloned lon genes from E. coli, Myxococcus xanthus, and Bacillus brevis. The predicted amino acid sequence of the E. amylovora Lon protease was 94, 59, and 54% identical to the predicted amino acid sequences of the Lon proteases of E. coli, M. xanthus, and B. brevis, respectively. The -10 and -35 promoter regions of the cloned lon gene had extensive homology to the respective consensus sequences of E. coli heat shock promoters. Promoter mapping of the lon gene located the start site 7 bases downstream of the -10 region. Cloning of the lon promoter upstream of a cat reporter gene demonstrated that expression of the E. amylovora lon gene was inducible by a heat shock. This is the first demonstration of a heat shock-regulated gene in E. amylovora. Site-directed mutagenesis of the -10 region of the lon promoter confirmed that the heat shock expression of the E. amylovora lon gene may be mediated by a sigma 32-like factor. Insertional inactivation of the E. amylovora chromosomal lon gene confirmed that the lon gene was not essential for either vegetative growth or infection of apple seedlings. E. amylovora lon mutants had increased sensitivity to UV irradiation and elevated levels of extracellular polysaccharide, suggesting comparable roles for the Lon proteases in both E. amylovora and E. coli. PMID- 7860604 TI - Identification of genes negatively regulated by Fis: Fis and RpoS comodulate growth-phase-dependent gene expression in Escherichia coli. AB - Fis is a nucleoid-associated protein in Escherichia coli that has been shown to regulate recombination, replication, and transcription reactions. It is expressed in a transient manner under batch culturing conditions such that high levels are present during early exponential phase and low levels are present during late exponential phase and stationary phase. We have screened a random collection of transposon-induced lac fusions for those which give decreased expression in the presence of Fis. Thirteen different Fis-repressed genes were identified, including glnQ (glutamine high-affinity transport), mglA (methyl-galactoside transport), xylF (D-xylose-binding protein), sdhA (succinate dehydrogenase flavoprotein subunit), and a newly identified aldehyde dehydrogenase, aldB. The LacZ expression patterns revealed that many of the fusions were maximally expressed at different stages of growth, including early log phase, mid- to late log phase, and stationary phase. The expression of some of the late-exponential- and stationary-phase genes was dependent on the RpoS sigma factor, whereas that of others was affected negatively by RpoS. We conclude that Fis negatively regulates a diverse set of genes and that RpoS can function to both activate and inhibit the expression of specific genes. PMID- 7860605 TI - Isolation and characterization of chemotaxis mutants and genes of Pseudomonas aeruginosa. AB - Two chemotaxis-defective mutants of Pseudomonas aeruginosa, designated PC1 and PC2, were selected by the swarm plate method after N-methyl-N'-nitro-N nitrosoguanidine mutagenesis. These mutants were fully motile but incapable of swarming, suggesting that they had a defect in the intracellular signalling pathway. Computer-assisted capillary assays confirmed that they failed to show behavioral responses to chemical stimuli, including peptone, methyl thiocyanate, and phosphate. Two chemotaxis genes were cloned by phenotypic complementation of PC1 and PC2. From nucleotide sequence analysis, one gene was found to encode a putative polypeptide that was homologous to the enteric CheZ protein, while the other gene was cheY, which had been previously reported (M. N. Starnbach and S. Lory, Mol. Microbiol. 6:459-469, 1992). Deletion and complementation analysis showed that PC1 was a cheY mutant, whereas PC2 had a double mutation in the cheY and cheZ genes. A chromosomal cheZ mutant, constructed by inserting a kanamycin resistance gene cassette into the wild-type gene, changed its swimming direction much more frequently than did wild-type strain PAO1. In contrast, cheY mutants were found to rarely reverse their swimming directions. PMID- 7860606 TI - Beta-galactosidase is inactivated by intermolecular disulfide bonds and is toxic when secreted to the periplasm of Escherichia coli. AB - The wild-type LamB-LacZ hybrid protein inhibits the export machinery upon induction when assayed by biochemical and genetic techniques, a phenotype referred to as hybrid protein jamming. This hybrid protein also renders cells sensitive to growth in the presence of the inducer maltose, presumably because of the jamming. We constructed a new version of this fusion by adding alkaline phosphatase, encoded by phoA, to the C terminus of the LamB-LacZ hybrid protein. This tripartite protein, LamB-LacZ-PhoA, is as toxic to cells as the hybrid LamB LacZ; however, it does not jam at temperatures greater than 33 degrees C. Extreme C-terminal sequences of LacZ function as a critical folding domain and are therefore responsible for stabilizing the LacZ structure. To determine if this region of LacZ is important for jamming, we recombined a late nonsense mutation (X90) onto the hybrid construct. We found the toxicity of this new hybrid, LamB LacZX90, to be nearly identical to that of the full-length protein, but it also does not jam the secretion machinery. This suggests that jamming is caused by LacZ folding. We found no inhibition of secretion in the tripartite and X90 fusion strains at 37 degrees C, suggesting that the toxicity of the new fusions is novel. Under these conditions, the tripartite and X90 fusion proteins form disulfide-bonded aggregates with high molecular weights in the periplasm. Accordingly, we believe that LacZ disrupts some essential function(s) in the periplasm. PMID- 7860607 TI - Characterization of four superoxide dismutase genes from a filamentous cyanobacterium. AB - By using an oligonucleotide probe constructed from a conserved region of amino acids located in the carboxyl-terminal end of superoxide dismutase (SOD) proteins, four SOD genes were cloned from the cyanobacterium Plectonema boryanum UTEX 485. One of these genes, designated sodB, encoded an FeSOD enzyme, while the remaining three genes, designated sodA1, sodA2, and sodA3, encoded MnSOD enzymes. To investigate the expression of these four genes, total cellular RNA was isolated from P. boryanum UTEX 485 cells grown under various conditions and RNA gel blot analysis was carried out. Results indicated that sodB and sodA1 were constitutively expressed, although sodB expression was partially repressed in cells grown under conditions of iron stress. sodA2 transcripts, which were not detectable in control cells, accumulated to high levels in cells treated with methyl viologen or in cells grown under conditions of iron or nitrogen stress. However, under microaerobic conditions, iron and nitrogen stress failed to induce sodA2, indicating that multiple factors affect the regulation of sodA2. While discrete transcripts were not detected for sodA3, hybridization was observed under a number of conditions, including those which increased the accumulation of sodA2 transcripts. Additionally, there were high levels of the sodA3 transcript detected in a P. boryanum UTEX 485 mutant strain resistant to methyl viologen treatment. PMID- 7860608 TI - Discrete amplifiable regions (amplicons) in the symbiotic plasmid of Rhizobium etli CFN42. AB - Frequent tandem amplification of defined regions of the genome, called amplicons, is a common characteristic in the genomes of some Rhizobium species, such as Rhizobium etli. In order to map these zones in a model Rhizobium replicon, we undertook an analysis of the plasticity patterns fostered by amplicons in the pSym (390 kb) of R. etli CFN42. Data presented in this article indicate the presence of four amplicons in pSym, used for the generation of tandem amplifications and deletions. The amplicons are large, ranging from 90 to 175 kb, and they are overlapping. Each amplicon is usually flanked by specific reiterated sequences. Formation of amplifications and deletions requires an active recA gene. All the amplicons detected are concentrated in a zone of roughly one-third of pSym, covering most of the symbiotic genes detected in this plasmid. No amplicons were detected in the remaining two-thirds of pSym. These data support the idea that most of the known symbiotic genes in this plasmid are located in a genomic region that is prone to the formation of frequent tandem amplification. PMID- 7860609 TI - The ars operon of Escherichia coli confers arsenical and antimonial resistance. AB - The chromosomally encoded arsenical resistance (ars) operon subcloned into a multicopy plasmid was found to confer a moderate level of resistance to arsenite and antimonite in Escherichia coli. When the operon was deleted from the chromosome, the cells exhibited hypersensitivity to arsenite, antimonite, and arsenate. Expression of the ars genes was inducible by arsenite. By Southern hybridization, the operon was found in all strains of E. coli examined but not in Salmonella typhimurium, Pseudomonas aeruginosa, or Bacillus subtilis. PMID- 7860610 TI - Mutational analysis of flagellum-independent surface spreading of Serratia marcescens 274 on a low-agar medium. AB - In a previous study (J. O'Rear, L. Alberti, and R. M. Harshey, J. Bacteriol. 174:6125-6137, 1992) we reported the isolation of several transposon mutants of Serratia marcescens 274 that were defective either in swarming alone or in both swimming and swarming motility. All the nonflagellate (Fla-) mutants, while defective in both types of motility, were able to spread rapidly on the surface of low-agar (0.35%) media. We show here that some of the swarming-defective mutants are defective in the production of serrawettin W1, an extracellular cyclic lipopeptide produced by S. marcescens 274. When combined with a Fla defect, the serrawettin (Swt) mutants are deficient in spreading on low-agar media. The spreading deficiency can be overcome by serrawettin supplied extracellularly. Introduction of Fla defects into chemotaxis mutants does not affect this mode of surface translocation. These results suggest that spreading may be a passive form of translocation. We also report that swarming defects in all mutants showing a Dps phenotype (able to swarm within the inoculated area but unable to move outward) in the earlier study can be overcome by changing the commercial source of agar. PMID- 7860611 TI - Beta-lactam-induced bacteriolysis of amino acid-deprived Escherichia coli is dependent on phospholipid synthesis. AB - The penicillin tolerance of amino acid-deprived relA+ Escherichia coli is attributed to the stringent response; i.e., relaxation of the stringent response suppresses penicillin tolerance. The beta-lactam-induced lysis of amino acid deprived bacteria resulting from relaxation of the stringent response was inhibited by cerulenin, or by glycerol deprivation in the case of a gpsA mutant (defective in the biosynthetic sn-glycerol 3-phosphate dehydrogenase). Therefore, beta-lactam-induced lysis of amino acid-deprived cells was dependent on phospholipid synthesis. The lysis process during amino acid deprivation can be experimentally dissociated into two stages designated the priming stage (during which the interaction between the beta-lactam and the penicillin-binding proteins occurs) and the beta-lactam-independent lysis induction stage. Both stages were shown to require phospholipid synthesis. It has been known for some time that the inhibition of phospholipid synthesis is among the plethora of physiological changes resulting from the stringent response. These results indicate that the inhibition of peptidoglycan synthesis and the penicillin tolerance associated with the stringent response are both secondary consequences of the inhibition of phospholipid synthesis. PMID- 7860613 TI - Nasal cancer in leather workers: an occupational disease. AB - Nasal cancer has a number of causative agents; exposures to most of the established nasal carcinogens occur in the workplace. An increased risk of nasal cancer has been ascertained in shoe-making and shoe-repairing, but the results for leather goods manufacture and leather tanning don't provide adequate evidence of carcinogenicity. Findings from two epidemiological studies carried out in Italy (a case/control study and a case/series report) add further information on this issue. The case/control study was performed in the provinces of Siena (Tuscany), Verona and Vicenza (Venetia) including 96 cases and 378 controls. A significant increased risk (Odds Ratio: 6.8; 90% C.I. = 1.9-25) of sinonasal cancer was found for the employ in the whole leather industry; Odds Ratio of 8.3 (C.I. = 1.9-36) and 5.0 (C.I. = 0.92-28) were associated with shoe-making and leather tanning. The case/series report is based on 110 patients accepted in some Italian hospitals during last three years (1990-1993): 26 cases had worked in the leather industry; adenocarcinoma is the most frequent type observed. Chromium salts and natural tannins are indicated as possible aetiological agents. PMID- 7860612 TI - Role of outer membrane barrier in efflux-mediated tetracycline resistance of Escherichia coli. AB - Accumulation of tetracycline in Escherichia coli was studied to determine its permeation pathway and to provide a basis for understanding efflux-mediated resistance. Passage of tetracycline across the outer membrane appeared to occur preferentially via the porin OmpF, with tetracycline in its magnesium-bound form. Rapid efflux of magnesium-chelated tetracycline from the periplasm was observed. In E. coli cells that do not contain exogenous tetracycline resistance genes, the steady-state level of tetracycline accumulation was decreased when porins were absent or when the fraction of Mg(2+)-chelated tetracycline was small. This is best explained by assuming the presence of a low-level endogenous active efflux system that bypasses the outer membrane barrier. When influx of tetracycline is slowed, this efflux is able to reduce the accumulation of tetracycline in the cytoplasm. In contrast, we found no evidence of a special outer membrane bypass mechanism for high-level efflux via the Tet protein, which is an inner membrane efflux pump coded for by exogenous tetA genes. Fractionation and equilibrium density gradient centrifugation experiments showed that the Tet protein is not localized to regions of inner and outer membrane adhesion. Furthermore, a high concentration of tetracycline was found in the compartment that rapidly equilibrated with the medium, most probably the periplasm, of Tet-containing E. coli cells, and the level of tetracycline accumulation in Tet-containing cells was not diminished by the mutational loss of the OmpF porin. These results suggest that the Tet protein, in contrast to the endogenous efflux system(s), pumps magnesium-chelated tetracycline into the periplasm. A quantitative model of tetracycline fluxes in E. coli cells of various types is presented. PMID- 7860614 TI - Varied expression of major histocompatibility complex and oncogenes in Shope carcinoma cell lines derived from a single tumor. AB - The cellular gene expression was compared in four Shope carcinoma cell lines, which were derived from a single tumor and possess various potentials for differentiation and tumorigenicity. The E6 and E7 transforming genes of cottontail rabbit papillomavirus were expressed in all these cell lines, highest level of expression being in the most tumorigenic and undifferentiated cell line, where the major histocompatibility complex (MHC) class I expression was the lowest. The MHC class II antigen, which is not expressed on normal epithelial cells, was detected in all the cell lines, but hardly, if at all, on the surface of these cells. The surface expression of the MHC class II antigen could not be induced by the culture supernatant of phytohaemagglutinin-stimulated splenocytes, which increased the surface expression level of the MHC class I antigen of the same cells. These findings suggest that the aberrant expression of the MHC class II antigen in these cells could not be implicated in the immune response against tumors. The c-fos, c-myc and c-H-ras oncogenes were variably expressed in these cell lines, but there was no correlation with tumorigenicity. PMID- 7860615 TI - Analysis of ras mutations in human melanocytic lesions: activation of the ras gene seems to be associated with the nodular type of human malignant melanoma. AB - We have analyzed the Ha-ras, Ki-ras and N-ras gene for point mutations at codons 12, 13 and 61 via restriction fragment length polymorphism/polymerase chain reaction analysis and subsequent direct sequencing in non-cultured fresh-frozen tissues of 16 superficial spreading melanomas (SSM), 13 nodular malignant melanomas (NMM), 2 lentigo malignant melanomas (LMM), 1 dysplastic nevus, 1 congenital nevus and 5 normal nevi from 38 patients. Mutations were found in 4 melanoma samples, all belonging to the nodular malignant type. Three of them were mutated in N-ras and one in the Ha-ras gene. Mutation in N-ras was also detected in the congenital nevus. All mutations were exclusively located at the first two base pairs of codon 61. No Ki-ras mutation was detected in any lesion. No mutation could be found in SSM and LMM in addition to dysplastic and normal nevi. The frequency of ras mutation in NMM was 31%, whereas in SSM it was 0%. Our study suggests (a) an association between ras mutations (mainly N-ras) and the NMM as a subgroup of human melanoma; (b) that activation of Ki-ras is not involved in the pathogenesis of melanoma. The role of UV radiation in point mutations of ras genes in human melanoma is discussed. PMID- 7860616 TI - Chemical stability, biological activity and cellular uptake of a cisplatin analogue having a 1,2-diarylethyleneamine ligand in cultures of human breast cancer cells. AB - The platinum(II) complex PtCl2(meso-6), which has the estrogenic ligand meso-1,2 bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine (meso-6), has been reported to be an effective antitumor drug for estrogen-receptor(ER)-positive tumors in animal experiments. The goal of this study was to investigate whether the observed biological effects could be ascribed to the intact PtCl2(meso-6). Cultures of the ER-positive human breast cancer cell line MCF-7 were used as the in vitro test system. In culture medium containing 10% fetal calf serum, PtCl2(meso-6) had a half-life of about 2 h, as determined by HPLC analysis, and no PtCl2(meso-6) was detectable after 10 h. The Pt complex bound irreversibly to serum protein. After 30 min, the diamine ligand was found released, with a maximum conversion of about 35% at 24 h. At this time the culture medium still had estrogenic activity, i.e. it induced ER processing in the MCF-7 cells. This indicates that the estrogenic effect was elicited by the released diamine ligand. In contrast, the growth-inhibitory activity of the medium preincubated with PtCl2(meso-6) was lost at a rate similar to the rate of loss of PtCl2(meso-6) from the medium. This accords with the platinum complex being the main cytotoxic entity. When MCF-7 cells were incubated with PtCl2([3H]meso-6), no free Pt complex could be identified in cellular extracts, and most of the cell-associated radioactivity coeluted with meso-6 in HPLC analysis. After 12 h, only 1.4% of the total cellular platinum was bound to DNA, but no tritium label could be detected. In conclusion, diamine ligand is released from the Pt(II) complex and can account for the estrogenic effects so far ascribed to PtCl2(meso-6). PMID- 7860617 TI - Interleukin-2 gene therapy of residual EL-4 leukaemia potentiates the effect of cyclophosphamide pretreatment. AB - Experiments were designed to investigate a possible therapeutic role of interleukin-2 (IL-2) gene transfer in the model of murine (EL-4) leukaemia pretreated with cyclophosphamide. It has been found that i.p. pretreatment of the leukaemic mice with cyclophosphamide, followed by i.v. administration of irradiated cells, genetically engineered to produce IL-2 and used as a source of the cytokine (IR-IL-2 cells), cured a substantial percentage of the leukaemic mice. Neither treatment with cyclophosphamide nor administration of the IR-IL-2 cells alone had any significant therapeutic effect. Labelling of the EL-4 and IR IL-2 cells with different fluorescent cell linkers followed by i.v. injection and detection of the labelled cells in cryostat sections of various organs has shown that both cell populations can be detected almost exclusively in the red pulp of the spleen, close to the white pulp nodules, thus providing the possibility of short-range local interactions among the IL-2-producing cells, IL-2-responsive defence effector cells and EL-4 leukaemia targets. PMID- 7860618 TI - Reduced expression of retinoblastoma (Rb) gene protein is related to cell proliferation and prognosis in transitional-cell bladder cancer. AB - Archival biopsy specimens from transitional-cell bladder cancers (n = 222) were analysed immunohisto-chemically for expression of retinoblastoma (Rb) gene protein. The intensity of staining for Rb protein and the fraction of positive nuclei were analysed and related to several other prognostic factors and survival. Six per cent of the tumours were totally negative for Rb protein and abnormal (weak) expression was found in 40% of cases. The fraction of positive nuclei and abnormal expression (weak) were highly significantly interrelated (P < 0.0001). A low value for the fraction of Rb-protein-positive nuclei was related to a large fraction in S phase (P = 0.001), high mitotic index (P = 0.016) and overexpression of epidermal growth factor receptor (P = 0.034) and p53 protein (P = 0.019). A normal Rb protein expression pattern was related to low S-phase values (P = 0.0001) whereas over-expression of p53 was related to high S-phase values (P = 0.0077). Morphometrically measured nuclear atypia and the fraction of Rb-protein-positive nuclei were negatively correlated (P < 0.05). In univariate survival analysis altered expression of Rb protein (P = 0.07) and low frequency (< or = 50%) of Rb-protein-positive nuclei (P = 0.0128) predicted a poor outcome. In a multivariate analysis, reduced expression of Rb protein had no independent prognostic value over T category, papillary status and the size of the S-phase fraction. The results show that tumor-suppressor genes Rb and p53 participate in the growth regulation of human bladder cancer cells in vivo and accordingly modify the prognosis. PMID- 7860619 TI - Primary gastric non-Hodgkin's lymphoma: a clinicopathological study of 41 patients. AB - Pathological findings in 41 patients (male/female ratio: 1.3/1) with primary localized gastric non-Hodgkin's lymphoma (NHL) were retrospectively studied and correlated with survival. The median observation period after diagnosis was 32 (0 189) months. Nineteen patients were low-grade NHL, all but one B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) type. Twenty-two patients had primary (n = 7) or secondary (n = 15) high-grade lymphomas; Musshoff stage IE was found in 29 and IIE in 12 cases. The median age at diagnosis was 61 years (range, 26-88 years), and proliferation, measured by the number of mitosis and Ki-67 antigen positivity (MIB-1), was high or moderately high in 24 cases and low in 17 cases. Follicular lymphatic hyperplasia could be found in 25 of 34 evaluable cases, more often in low-grade than in high-grade NHL. Most of the patients were treated by resective surgery and additional ratio- or chemotherapy. Thirteen patients (31%) died (median survival: 10 months), 5 of them within 3 months after surgery owing to postoperative complications. Survival was superior, though not statistically significant, in low-grade lymphomas. Our retrospective analysis of heterogeneously treated gastric lymphomas reveals that gastric lymphomas, especially of the low-grade MALT type, often remain a localized disease with a good long-term prognosis. Our study confirms previous reports indicating that lymphomas of the MALT type represent a specific clinicopathological entity. PMID- 7860620 TI - Spontaneous transient remission of disseminated histiocytosis X during pregnancy. AB - Disseminated histiocytosis X with cutaneous and lymph node involvement was diagnosed in a 25-year-old women. The diagnosis was established on the basis of a positive cell-surface staining with OKT 6 and typical signs on electron microscopy. Both the specific skin rash and lymph node swelling completely disappeared during pregnancy, but recurred 2 weeks before delivery. Therapeutic trials with 0.25 mg ethinylestradiol/day and a later application of human chorionic gonadotropin up to 5000 IU i.m. twice weekly as well as prednisolone 25 mg three times per day were unsuccessful. A second pregnancy was not desired. Polychemotherapy with initial high-dose prednisolone plus vincristine and a consolidation therapy with 5-mercaptopurine 300 mg/day led to full recovery. The observation of transient remission of histiocytosis X during pregnancy suggests that at least some forms of this disease may have prevailing immunological features where an immunosuppressive effect of pregnancy could be beneficial. PMID- 7860621 TI - A study of serum glycosidases in cancer. AB - N-Acetyl-beta-glucosaminidase (NAG) and beta-glucuronidase were measured in the serum of 70 patients with breast and digestive-tract neoplasms and in 70 healthy subjects. The mean value of the NAG activity was significantly (P < 0.001) elevated in patients with gastric, liver and pancreas cancer as compared with the reference population. In patients with liver and pancreas cancer the very high sensitivity contrasted with a low specificity. NAG elevations above normal were observed in 14 (78%) patients with breast cancer, in 11 (100%) with gastric cancer, in 17 (70%) with colorectal cancer, in 8 (100%) with liver cancer and in 9 (100%) with pancreas cancer. In patients with breast and gastric cancer the enzyme shows a good specificity and sufficient sensitivity as a tumor marker. beta-Glucuronidase appeared less sensitive and was significantly elevated (100%) only in patients with pancreas cancer. PMID- 7860622 TI - Identification of immunoreactive tissue kallikrein in human ductal breast carcinomas. AB - Various proteases have been shown to be present in malignant breast tissue. Although the question of the involvement of tissue kallikrein, a serine protease, in the pathophysiology of tumours has been raised, the presence of this enzyme in human breast carcinoma has so far not been examined. In the present study, both neoplastic and normal human breast are scanned by immunocytochemistry for the presence and cellular localization of tissue kallikrein. In the healthy breast, tissue kallikrein was observed as a deposit of immunoreactive material that localized in the apical portion of duct cells. In the malignant breast tumours surveyed, the enzyme was observed only in ductal carcinomas, whereas lobular carcinomas were devoid of immunostaining. In ductal carcinomas, the immunoreactivity for tissue kallikrein appeared to be associated with gradations of malignancy, being absent in dedifferentiated tumours. The presence of tissue kallikrein in malignant breast tumours poses the question of the role of this enzyme in malignant breast tissue. The enzyme may participate within the tissue either in proteolytic processes (it has been shown to activate procollagenase) or by enhancing vascularity or mitogenicity by the generation of kinins. PMID- 7860623 TI - Low frequency and late occurrence of p53 and dcc aberrations in colorectal tumours. AB - Whilst p53 aberrations have been documented in numerous malignancies, reports of alterations to the deleted in colorectal cancer (dcc) gene are infrequent, and studies investigating the status of both genes in the same colon tumour are rare. In this study we have analysed a panel of 35 pairs of normal and neoplastic human colorectal tissues for abnormalities in these tumour-suppressor genes. In contrast to previous studies we have found only a low incidence of mutations and deletions. p53 point mutations were identified in 8/35 tumours (22%). All were G.C to A.T transitions, with 7/8 occurring at CpG dinucleotides. p53 allelic loss was detected in 4/11 informative cases (36%). Although not quite attaining statistical significance, p53 alteration correlated with the adenoma/carcinoma transition. Gross dcc alterations were identified by Southern blotting in 7/35 (20%) tumours. Microsatellite analysis using two markers, one within and one proximal to the dcc gene, detected a low frequency of deletion overall (41% informative cases). 18q/dcc aberrations were associated with the progression of early to late carcinoma, rather than with increasing adenoma size, as has been previously reported. Both p53 alterations and dcc deletions were detected at a higher frequency in distal tumours than in proximal malignancies. Two tumours exhibiting microsatellite instability in both markers were each of proximal origin. PMID- 7860624 TI - A novel cis-acting centromeric DNA element affects S. pombe centromeric chromatin structure at a distance. AB - The chromatin structure of the central core region of Schizosaccharomyces pombe centromeric DNA is unusual. This distinctive chromatin structure is associated only with central core sequences in a functional context and is modulated by a novel cis-acting DNA element (centromere enhancer) within the functionally critical K centromeric repeat, which is found in multiple copies in all three S. pombe centromeres. The centromere enhancer alters central core chromatin structure from a distance and in an orientation-independent manner without altering the nucleosomal packaging of sequences between the enhancer and the central core. These findings suggest a functionally relevant structural interaction between the enhancer and the centromeric central core brought about by DNA looping. PMID- 7860625 TI - Zip1-induced changes in synaptonemal complex structure and polycomplex assembly. AB - The yeast Zip1 protein is a component of the synaptonemal complex (SC), which is an elaborate macromolecular structure found along the lengths of chromosomes during meiosis. Mutations that increase the length of the predicted coiled coil region of the Zip1 protein show that Zip1 influences the width of the SC. Overexpression of the ZIP1 gene results in the formation of two distinct types of higher order structures that are found in the nucleus, but not associated with chromatin. One of these structures resembles the polycomplexes that have been observed in many organisms and are thought to be aggregates of SC components. The second type of structure, which we have termed "networks," does not resemble any previously identified SC-related structure. Assembly of both polycomplexes and networks can occur independently of the Hop1 or Red1 protein, which are thought to be SC components. Our results demonstrate that Zip1 is a structural component of the central region of the SC. More specifically, we speculate that Zip1 is a component of the transverse filaments that lie perpendicular to the long axis of the complex. PMID- 7860626 TI - Aspergillus nidulans apsA (anucleate primary sterigmata) encodes a coiled-coil protein required for nuclear positioning and completion of asexual development. AB - Many fungi are capable of growing by polarized cellular extension to form hyphae or by isotropic expansion to form buds. Aspergillus nidulans anucleate primary sterigmata (apsA) mutants are defective in nuclear distribution in both hyphae and in specialized, multicellular reproductive structures, called conidiophores. apsA mutations have a negligible effect on hyphal growth, unlike another class of nuclear distribution (nud) mutants. By contrast, they almost completely block entry of nuclei into primary buds, or sterigmata (bud nucleation), produced during development of conidiophores. Failure of the primary sterigmata to become nucleated results in developmental arrest and a failure to activate the transcriptional program associated with downstream developmental steps. However, occasionally in mutants a nucleus enters a primary bud and this event relieves the developmental blockage. Thus, there is a stringent developmental requirement for apsA function, but only at the stage of primary bud formation. apsA encodes a 183-kD coiled-coil protein with similarity to Saccharomyces cerevisiae NUM1p, required for nuclear migration in the budding process. PMID- 7860628 TI - The alpha subunit of the Saccharomyces cerevisiae oligosaccharyltransferase complex is essential for vegetative growth of yeast and is homologous to mammalian ribophorin I. AB - Oligosaccharyltransferase mediates the transfer of a preassembled high mannose oligosaccharide from a lipid-linked oligosaccharide donor to consensus glycosylation acceptor sites in newly synthesized proteins in the lumen of the rough endoplasmic reticulum. The Saccharomyces cerevisiae oligosaccharyltransferase is an oligomeric complex composed of six nonidentical subunits (alpha-zeta), two of which are glycoproteins (alpha and beta). The beta and delta subunits of the oligosaccharyltransferase are encoded by the WBP1 and SWP1 genes. Here we describe the functional characterization of the OST1 gene that encodes the alpha subunit of the oligosaccharyltransferase. Protein sequence analysis revealed a significant sequence identity between the Saccharomyces cerevisiae Ost1 protein and ribophorin I, a previously identified subunit of the mammalian oligosaccharyltransferase. A disruption of the OST1 locus was not tolerated in haploid yeast showing that expression of the Ost1 protein is essential for vegetative growth of yeast. An analysis of a series of conditional ost1 mutants demonstrated that defects in the Ost1 protein cause pleiotropic underglycosylation of soluble and membrane-bound glycoproteins at both the permissive and restrictive growth temperatures. Microsomal membranes isolated from ost1 mutant yeast showed marked reductions in the in vitro transfer of high mannose oligosaccharide from exogenous lipid-linked oligosaccharide to a glycosylation site acceptor tripeptide. Microsomal membranes isolated from the ost1 mutants contained elevated amounts of the Kar2 stress-response protein. PMID- 7860627 TI - Giant peroxisomes in oleic acid-induced Saccharomyces cerevisiae lacking the peroxisomal membrane protein Pmp27p. AB - We have purified peroxisomal membranes from Saccharomyces cerevisiae after induction of peroxisomes in oleic acid-containing media. About 30 distinct proteins could be discerned among the HPLC- and SDS-PAGE-separated proteins of the high salt-extracted peroxisomal membranes. The most abundant of these, Pmp27p, was purified and the corresponding gene PMP27 was cloned and sequenced. Its primary structure is 32% identical to PMP31 and PMP32 of the yeast Candida biodinii (Moreno, M., R. Lark, K. L. Campbell, and M. J. Goodman. 1994. Yeast. 10:1447-1457). Immunoelectron microscopic localization of Pmp27p showed labeling of the peroxisomal membrane, but also of matrix-less and matrix containing tubular membranes nearby. Electronmicroscopical data suggest that some of these tubular extensions might interconnect peroxisomes to form a peroxisomal reticulum. Cells with a disrupted PMP27 gene (delta pmp27) still grew well on glucose or ethanol, but they failed to grow on oleate although peroxisomes were still induced by transfer to oleate-containing media. The induced peroxisomes of delta pmp27 cells were fewer but considerably larger than those of wild-type cells, suggesting that Pmp27p may be involved in parceling of peroxisomes into regular quanta. delta pmp27 cells cultured in oleate-containing media form multiple buds, of which virtually all are peroxisome deficient. The growth defect of delta pmp27 cells on oleic acid appears to result from the inability to segregate the giant peroxisomes to daughter cells. PMID- 7860629 TI - Polarized sorting of beta-amyloid precursor protein and its proteolytic products in MDCK cells is regulated by two independent signals. AB - Progressive cerebral deposition of the amyloid (A beta) beta-protein is an early and invariant feature of Alzheimer's disease. A beta is derived by proteolysis from the membrane-spanning beta-amyloid precursor protein (beta APP). beta APP is processed into various secreted products, including soluble beta APP (APPs), the 4-kD A beta peptide, and a related 3-kD peptide (p3). We analyzed the mechanisms regulating the polarized basolateral sorting of beta APP and its proteolytic derivatives in MDCK cells. Deletion of the last 32 amino acids (residues 664-695) of the beta APP cytoplasmic tail had no influence on either the constitutive approximately 90% level of basolateral sorting of surface beta APP, or the strong basolateral secretion of APPs, A beta, and p3. However, deleting the last 42 amino acids (residues 654-695) or changing tyrosine 653 to alanine altered the distribution of cell surface beta APP so that approximately 40-50% of the molecules were inserted apically. In parallel, A beta was now secreted from both surfaces. Surprisingly, this change in surface beta APP had no influence on the basolateral secretion of APPs and p3. This result suggests that most beta APP molecules which give rise to APPs in MDCK cells are cleaved intracellularly before reaching the surface. Consistent with this conclusion, we readily detected intracellular APPs in carbonate extracts of isolated membrane vesicles. Moreover, ammonium chloride treatment resulted in the equal secretion of APPs into both compartments, as occurs with other non-membranous, basolaterally secreted proteins, but it did not influence the polarity of cell surface beta APP. These results demonstrate that in epithelial cells two independent mechanisms mediate the polarized trafficking of beta APP holoprotein and its major secreted derivative (APPs) and that A beta peptides are derived in part from beta APP holoprotein targeted to the cell surface by a signal that includes tyrosine 653. PMID- 7860630 TI - Evidence for nonvectorial, retrograde transferrin trafficking in the early endosomes of HEp2 cells. AB - We have previously characterized the trafficking of transferrin (Tf) through HEp2 human carcinoma cells (Ghosh, R. N., D. L. Gelman, and F. R. Maxfield, 1994. J. Cell Sci. 107:2177-2189). Early endosomes in these cells are comprised of both sorting endosomes and recycling compartments, which are distinct separate compartments. Endocytosed Tf initially appears in punctate sorting endosomes that also contain recently endocytosed LDL. After short loading pulses, Tf rapidly sorts from LDL with first-order kinetics (t1/2 approximately 2.5 min), and it enters the recycling compartment before leaving the cell (t1/2 approximately 7 min). Here, we report a second, slower rate for Tf to leave sorting endosomes after HEp2 cells were labeled to steady state with fluorescein Tf instead of the brief pulse used previously. We determined this rate using digital image analysis to measure the Tf content of sorting endosomes that also contained LDL. With an 11-min chase, the Tf in sorting endosomes was 24% of steady-state value. This was in excess of the amount expected (5% of steady state) from the rate of Tf exit after short filling pulses. The excess could not be accounted for by reinternalization of recycled cell surface Tf, implying that either some Tf was retained in sorting endosomes, or that Tf was delivered back to the sorting endosomes from the recycling compartment. The former is unlikely since nearly all sorting endosomes contain detectable Tf after an 11-min chase, even though more than one third of the sorting endosomes were formed during the chase time. Furthermore, while observing living cells by confocal microscopy, we saw vesicle movements that appeared to be fluorescent Tf returning from recycling compartments to sorting endosomes. The slow rate of exit after steady-state labeling was similar to the Tf exit rate from the cell, suggesting an equilibration of Tf throughout the early endosomal system by this retrograde pathway. This retrograde traffic may be important for delivering molecules from the recycling compartment, which is a long-lived organelle, to sorting endosomes, which are transient. PMID- 7860631 TI - myoA of Aspergillus nidulans encodes an essential myosin I required for secretion and polarized growth. AB - We have identified and cloned a novel essential myosin I in Aspergillus nidulans called myoA. The 1,249-amino acid predicted polypeptide encoded by myoA is most similar to the amoeboid myosins I. Using affinity-purified antibodies against the unique myosin I carboxyl terminus, we have determined that MYOA is enriched at growing hyphal tips. Disruption of myoA by homologous recombination resulted in a diploid strain heterozygous for the myoA gene disruption. We can recover haploids with an intact myoA gene from these strains, but never haploids that are myoA disrupted. These data indicated that myoA encodes an essential myosin I, and this has allowed us to use a unique approach to studying myosin I function. We have developed conditionally null myoA strains in which myoA expression is regulated by the alcA alcohol dehydrogenase promoter. A conditionally lethal strain germinated on inducing medium grows as wild type, displaying polarized growth by apical extension. However, growth of the same myoA mutant strain on repressing medium results in enlarged cells incapable of hyphal extension, and these cells eventually die. Under repressing conditions, this strain also displays reduced levels of secreted acid phosphatase. The mutant phenotype indicates that myoA plays a critical role in polarized growth and secretion. PMID- 7860632 TI - Actin filament disassembly is a sufficient final trigger for exocytosis in nonexcitable cells. AB - Although the actin cytoskeleton has been implicated in vesicle trafficking, docking and fusion, its site of action and relation to the Ca(2+)-mediated activation of the docking and fusion machinery have not been elucidated. In this study, we examined the role of actin filaments in regulated exocytosis by introducing highly specific actin monomer-binding proteins, the beta-thymosins or a gelsolin fragment, into streptolysin O-permeabilized pancreatic acinar cells. These proteins had stimulatory and inhibitory effects. Low concentrations elicited rapid and robust exocytosis with a profile comparable to the initial phase of regulated exocytosis, but without raising [Ca2+], and even when [Ca2+] was clamped at low levels by EGTA. No additional cofactors were required. Direct visualization and quantitation of actin filaments showed that beta-thymosin, like agonists, induced actin depolymerization at the apical membrane where exocytosis occurs. Blocking actin depolymerization by phalloidin or neutralizing beta thymosin by complexing with exogenous actin prevented exocytosis. These findings show that the cortical actin network acts as a dominant negative clamp which blocks constitutive exocytosis. In addition, actin filaments also have a positive role. High concentrations of the actin depolymerizing proteins inhibited all phases of exocytosis. The inhibition overrides stimulation by agonists and all downstream effectors tested, suggesting that exocytosis cannot occur without a minimal actin cytoskeletal structure. PMID- 7860633 TI - Regulation of cortical actin cytoskeleton assembly during polarized cell growth in budding yeast. AB - We have established an in vitro assay for assembly of the cortical actin cytoskeleton of budding yeast cells. After permeabilization of yeast by a novel procedure designed to maintain the spatial organization of cellular constituents, exogenously added fluorescently labeled actin monomers assemble into distinct structures in a pattern that is similar to the cortical actin distribution in vivo. Actin assembly in the bud of small-budded cells requires a nucleation activity provided by protein factors that appear to be distinct from the barbed ends of endogenous actin filaments. This nucleation activity is lost in cells that lack either Sla1 or Sla2, proteins previously implicated in cortical actin cytoskeleton function, suggesting a possible role for these proteins in the nucleation reaction. The rate and the extent of actin assembly in the bud are increased in permeabilized delta cap2 cells, providing evidence that capping protein regulates the ability of the barbed ends of actin filaments to grow in yeast cells. Actin incorporation in the bud can be stimulated by treating the permeabilized cells with GTP-gamma S, and, significantly, the stimulatory effect is eliminated by a mutation in CDC42, a gene that encodes a Rho-like GTP-binding protein required for bud formation. Furthermore, the lack of actin nucleation activity in the cdc42 mutant can be complemented in vitro by a constitutively active Cdc42 protein. These results suggest that Cdc42 is closely involved in regulating actin assembly during polarized cell growth. PMID- 7860634 TI - Saccharomyces cerevisiae kinesin- and dynein-related proteins required for anaphase chromosome segregation. AB - The Saccharomyces cerevisiae kinesin-related gene products Cin8p and Kip1p function to assemble the bipolar mitotic spindle. The cytoplasmic dynein heavy chain homologue Dyn1p (also known as Dhc1p) participates in proper cellular positioning of the spindle. In this study, the roles of these motor proteins in anaphase chromosome segregation were examined. While no single motor was essential, loss of function of all three completely halted anaphase chromatin separation. As combined motor activity was diminished by mutation, both the velocity and extent of chromatin movement were reduced, suggesting a direct role for all three motors in generating a chromosome-separating force. Redundancy for function between different types of microtubule-based motor proteins was also indicated by the observation that cin8 dyn1 double-deletion mutants are inviable. Our findings indicate that the bulk of anaphase chromosome segregation in S. cerevisiae is accomplished by the combined actions of these three motors. PMID- 7860636 TI - The t-SNAREs syntaxin 1 and SNAP-25 are present on organelles that participate in synaptic vesicle recycling. AB - Syntaxin 1 and synaptosome-associated protein of 25 kD (SNAP-25) are neuronal plasmalemma proteins that appear to be essential for exocytosis of synaptic vesicles (SVs). Both proteins form a complex with synaptobrevin, an intrinsic membrane protein of SVs. This binding is thought to be responsible for vesicle docking and apparently precedes membrane fusion. According to the current concept, syntaxin 1 and SNAP-25 are members of larger protein families, collectively designated as target-SNAP receptors (t-SNAREs), whose specific localization to subcellular membranes define where transport vesicles bind and fuse. Here we demonstrate that major pools of syntaxin 1 and SNAP-25 recycle with SVs. Both proteins cofractionate with SVs and clathrin-coated vesicles upon subcellular fractionation. Using recombinant proteins as standards for quantitation, we found that syntaxin 1 and SNAP-25 each comprise approximately 3% of the total protein in highly purified SVs. Thus, both proteins are significant components of SVs although less abundant than synaptobrevin (8.7% of the total protein). Immunoisolation of vesicles using synaptophysin and syntaxin specific antibodies revealed that most SVs contain syntaxin 1. The widespread distribution of both syntaxin 1 and SNAP-25 on SVs was further confirmed by immunogold electron microscopy. Botulinum neurotoxin C1, a toxin that blocks exocytosis by proteolyzing syntaxin 1, preferentially cleaves vesicular syntaxin 1. We conclude that t-SNAREs participate in SV recycling in what may be functionally distinct forms. PMID- 7860635 TI - Acetylcholine receptor-aggregating activity of agrin isoforms and mapping of the active site. AB - Agrin is a basal lamina protein that induces aggregation of acetylcholine receptors (AChRs) and other molecules at the developing neuromuscular junction. Alternative splicing of chick agrin mRNA at two sites, A and B, gives rise to eight possible isoforms of which five are expressed in vivo. Motor neurons express high levels of isoforms with inserts at sites A and B, muscle cells synthesize isoforms that lack amino acids at the B-site. To obtain further insights into the mechanism of agrin-induced AChR aggregation, we have determined the EC50 (effective concentration to induce half-maximal AChR clustering) of each agrin isoform and of truncation mutants. On chick myotubes, EC50 of the COOH terminal, 95-kD fragment of agrinA4B8 was approximately 35 pM, of agrinA4B19 approximately 110 pM and of agrinA4B11 approximately 5 nM. While some AChR clusters were observed with 64 nM of agrinA4B0, no activity was detected for agrinA0B0. Recombinant full-length chick agrin and a 100-kD fragment of ray agrin showed similar EC50 values. A 45-kD, COOH-terminal fragment of agrinA4B8 retained high activity (EC50 approximately equal to 130 pM) and a 21-kD fragment was still active, but required higher concentrations (EC50 approximately equal to 13 nM). Unlike the 45-kD fragment, the 21-kD fragment neither bound to heparin nor did heparin inhibit its capability to induce AChR aggregation. These data show quantitatively that agrinA4B8 and agrinA4B19, expressed in motor neurons, are most active, while no activity is detected in agrinA0B0, the dominant isoform synthesized by muscle cells. Furthermore, our results show that a fragment comprising site B8 and the most COOH-terminal G-like domain is sufficient for this activity, and that agrin domains required for binding to heparin and those for AChR aggregation are distinct from each other. PMID- 7860637 TI - Absence of persistent spreading, branching, and adhesion in GAP-43-depleted growth cones. AB - The growth-associated protein GAP-43 is a major protein kinase C substrate of growth cones and developing nerve terminals. In the growth cone, it accumulates near the plasma membrane, where it associates with the cortical cytoskeleton and membranes. The role of GAP-43 in neurite outgrowth is not yet clear, but recent findings suggest that it may be a crucial competence factor in this process. To define the role of GAP-43 in growth cone activity, we have analyzed neurite outgrowth and growth cone activity in primary sensory neurons depleted of GAP-43 by a specific antisense oligonucleotide procedure. Under optimal culture conditions, but in the absence of GAP-43, growth cones adhered poorly, displayed highly dynamic but unstable lamellar extensions, and were strikingly devoid of local f-actin concentrations. Upon stimulation, they failed to produce NGF induced spreading or insulin-like growth factor-1-induced branching, whereas growth factor-induced phosphotyrosine immunoreactivity and acceleration of neurite elongation were not impaired. Unlike their GAP-43-expressing counterparts, they readily retracted when exposed to inhibitory central nervous system myelin-derived liposomes. Frequency and extent of induced retraction were attenuated by NGF. Our results indicate that GAP-43 can promote f-actin accumulation, evoked morphogenic activity, and resistance to retraction of the growth cone, suggesting that it may promote regulated neurite outgrowth during development and regeneration. PMID- 7860638 TI - Activation of protein kinase C inhibits ATP-induced [Ca2+]i elevation in rat osteoblastic cells: selective effects on P2Y and P2U signaling pathways. AB - Extracellular ATP elicits transient elevation of cytosolic free Ca2+ concentration ([Ca2+]i) in osteoblasts through interaction with more than one subtype of cell surface P2-purinoceptor. Elevation of [Ca2+]i arises, at least in part, by release of Ca2+ from intracellular stores. In the present study, we investigated the possible roles of protein kinase C (PKC) in regulating these signaling pathways. [Ca2+]i of indo-1-loaded UMR-106 osteoblastic cells was monitored by spectrofluorimetry. In the absence of extracellular Ca2+, ATP (100 microM) induced transient elevation of [Ca2+]i to a peak 57 +/- 7 nM above basal levels (31 +/- 2 nM, means +/- S.E.M., n = 25). Exposure of cells to the PKC activator 12-O-tetradecanoyl-beta-phorbol 13-acetate (TPA, 100 nM) for 2 min significantly reduced the amplitude of the ATP response to 13 +/- 4 nM (n = 11), without altering basal [Ca2+]i. Inhibition was half-maximal at approximately 1 nM TPA. The Ca2+ response to ATP was also inhibited by the PKC activators 1,2 dioctanoyl-sn-glycerol or 4 beta-phorbol 12,13-dibutyrate, but not by the control compounds 4 alpha-phorbol or 4 alpha-phorbol 12,13-didecanoate. Furthermore, exposure of cells to the protein kinase inhibitors H-7 or staurosporine for 10 min significantly attenuated the inhibitory effect of TPA. However, these protein kinase inhibitors did not prolong the [Ca2+]i response to ATP alone, indicating that activation of PKC does not account for the transient nature of this response. When the effects of other nucleotides were examined, TPA was found to cause significantly greater inhibition of the response to the P2Y-receptor agonists, ADP and 2-methylthioATP, than the response to the P2U-receptor agonist, UTP. These data indicate that activation of PKC selectively inhibits the P2Y signaling pathway in osteoblastic cells. In vivo, endocrine or paracrine factors, acting through PKC, may regulate the responsiveness of osteoblasts to extracellular nucleotides. PMID- 7860639 TI - Relationship between actions of transforming growth factor (TGF)-beta and cell surface expression of its receptors in clonal osteoblastic cells. AB - Various osteoblastic cell lines were examined for the relationship between the presence of cell-surface transforming growth factor (TGF)-beta receptors and the synthesis of matrix proteins with their responsiveness to TGF-beta. Treatment with TGF-beta 1 inhibited proliferation and stimulated proteoglycan and fibronectin synthesis in MC3T3-E1 and MG 63 cells. The major proteoglycans synthesized by these cells were decorin and biglycan, and TGF-beta 1 markedly stimulated the synthesis of decorin in MC3T3-E1 and of biglycan in MG 63 cells. SaOS 2 and UMR 106 cells synthesized barely detectable amounts of decorin or biglycan, and TGF-beta 1 did not stimulate the synthesis of these proteoglycans. In SaOS 2 cells, however, TGF-beta 1 enhanced fibronectin synthesis. TGF-beta 1 did not show any of these effects in UMR 106 cells. Receptor cross-linking studies revealed that only MC3T3-E1 and MG 63 cells had both types I and II signal-transducing receptors for TGF-beta in addition to betaglycan. SaOS 2 cells possessed type I but no type II receptor on the cell surface. In contrast, SaOS 2 as well as MC3T3-E1 and MG 63 cells expressed type II receptor mRNA by Northern blot analysis, and cell lysates contained type II receptor by Western blot analysis. Thus, it appears that type II receptor present in SaOS 2 cells is not able to bind TGF-beta 1 under these conditions. UMR 106 cells with no response to TGF-beta 1 had neither of the signal-transducing receptors by any of the analyses. These observations using clonal osteoblastic cell lines demonstrate that the ability of osteoblastic cells to synthesize bone matrix proteoglycans is associated with the responsiveness of these cells to TGF-beta 1, that the responsiveness of osteoblastic cells to TGF-beta 1 in cell proliferation and proteoglycan synthesis correlates with the presence of both types I and II receptors, and that the effect of TGF-beta 1 on fibronectin synthesis can develop with little binding of TGF-beta 1 to type II receptor if type I receptor is present. It is suggested that the combination of cell-surface receptors for TGF beta determines the responsiveness of osteoblastic cells to TGF-beta and that changes in cell-surface TGF-beta receptors may play a role in the regulation of matrix protein synthesis and bone formation in osteoblasts. PMID- 7860640 TI - Effect of an alkaline shift on induction of the heat shock response in human fibroblasts. AB - The simultaneous exposure of WI-38 human fibroblasts (HF) to a heat shock (45 degrees C, 30 min) and an alkaline shift (> or = pH 8.0) in the incubation medium increased and extended the expression of heat shock proteins (hsps). Hsp70 was the most prominent inducible hsp synthesized during the recovery phase after the double shock, and the increase in synthesis depended on the degree of alkalinization during the heat shock. The accumulation of inducible hsp70, which was shown by Western blotting to occur in the late part of the recovery period, was more pronounced in the cells exposed to alkaline medium during the heat shock. Northern blotting did not reveal any increase in hsp70 mRNA, although time course studies following the double shock indicated a more prolonged presence of mRNA. Hsp70 gene activation was evaluated by a gel retardation assay using a 32P labelled DNA oligonucleotide containing the heat shock consensus element (HSE) and a heat shock-induced specific binding protein (heat shock transcription factor, HSTF) from the cell extract. Heat shock activated HSTF-DNA binding and induced hsp70 mRNA expression as well as the synthesis and accumulation of hsp70. Alkaline shift, which by itself did not induce hsps expression, activated HSTF DNA-binding. However, in combination with heat shock, alkaline shift enhanced and prolonged HSTF-HSE complex association and hsp expression at both mRNA and protein levels. Since the alkaline shift-induced activation of hsp gene does not allow full transcription, these results provide further support for the multistep nature of the heat shock transcriptional response. PMID- 7860641 TI - Effects of mild heat shock on glycogenesis and its regulation by insulin in cultured fetal hepatocytes. AB - The effects of a mild heat shock were investigated using cultured 15-day-old fetal rat hepatocytes in which an acute glucocorticoid-dependent glycogenic response to insulin was present. After exposure from 15 min to 2 h at 42.5 degrees C, cell surface [125I]insulin binding progressively decreased down to 60% of the value shown in cells kept at 37 degrees C, due toa decrease in the apparent number of insulin binding sites with little change in insulin receptor affinity. In parallel cultures, protein labeling with [35S]methionine exhibited stimulated synthesis of specific proteins, in particular, 73-kDa Hsc (heat shock cognate) and 72-kDa Hsp (heat shock protein). When cells were returned to 37 degrees C after 2 h at 42.5 degrees C, cell surface insulin binding showed a two third restoration within 3 h (insulin receptor half-life = 13 h), with similar concomitant return of Hsps72,73 synthesis to preinduction levels. The rate of [14C]glucose incorporation into glycogen measured at 37 degrees C after 1- to 2-h heat treatment revealed a striking yet transient increase in basal glycogenesis (up to 5-fold). At the same time, the glycogenesis stimulation by insulin was reduced (from 3.2 to 1.4-fold), whereas that induced by a glucose load was maintained. Induction of thermotolerance after a first heating was obtained for the heat shock-dependent events except for the enhanced basal glycogenesis. In insulin-unresponsive cells grown in the absence of glucocorticoids, heat shock decreased the glycogenic capacity without modifying the glucose load stimulation, supporting the hypothesis that insulin and thermal stimulation of glycogenesis share at least part of the same pathway. Inverse variations were observed between Hsps72,73 synthesis and both cell surface insulin receptor level and insulin glycogenic response in fetal hepatocytes experiencing heat stress. PMID- 7860642 TI - Suppression of tumorigenicity, but not invasion, in glioblastoma/HeLa cell hybrids. AB - Somatic cell hybrids between SNB-19 human glioblastoma cells and human D98OR HeLa cells were produced and analyzed for their ability to form tumors in nude mice and to invade reconstituted extracellular matrix (Matrigel). Whereas both the SNB 19 and D98OR HeLa parental cells form tumors, four of six hybrid lines did not form tumors, even after periods up to six months, suggesting that each cell type can complement the tumorigenicity of the other. SNB-19 cells showed high rates of Matrigel invasion at all cell densities examined, whereas D98OR HeLa cells showed lower rates of invasion that were further reduced at high cell density. All six hybrid cell lines displayed a combination of these properties: at low cell density, the hybrids showed high rates of invasion, similar to the SNB-19 cells, but the invasion rate diminished at higher cell densities, similar to the D98OR HeLa cells. Taken together, these results provide new experimental evidence that several distinct genetic changes are involved in generating the tumorigenic and invasive phenotype of glioblastoma cells. PMID- 7860643 TI - EGF-mediated phosphorylation of extracellular signal-regulated kinases in osteoblastic cells. AB - Epidermal growth factor (EGF) induces a rapid increase in the phosphorylation of extracellular signal-regulated kinases (ERKs) in the human osteosarcoma osteoblastic cell line G292 and in primary cultures of rat osteoblastic cells. This phosphorylation is transient and time-dependent. Maximal stimulation is attained within 1 min in G292 and within 5 min in rat osteoblastic cells. Enzymatic activity in G292 cells is also induced rapidly after EGF stimulation. Western blot analysis revealed that enhancement of the phosphorylation of ERKs in the EGF-stimulated cells is not due to an increase in ERK protein, since EGF treatment does not lead to an increase in the absolute amount of ERKs present even after 2 days of stimulation. The pattern of expression of the ERKs observed in the two cell types differs in the apparent molecular weights observed. The most slowly migrating immunoreactive protein (approximately 45 kDa) in normal rat osteoblastic cells is ERK1, identified by an ERK1-selective antiserum. The same antiserum reacts only weakly with one of the ERK proteins (44 kDa) blotted from the human osteosarcoma cell line G292. Phorbol 12-myristate 13-acetate (PMA) is also capable of inducing ERK phosphorylation, albeit to a lasser degree. The combination of PMA and EGF does not produce a greater response than EGF alone. The role of protein kinase C (PKC) in the EGF-stimulated ERK signaling pathway was further examined by inhibition of PKC with the staurosporine analog, CGP41251, and by down-regulation of PKC via chronic treatment with PMA. Chronic PMA treatment results in a partial inhibition of the EGF-mediated phosphorylation. CGP41251 completely abolishes the increased ERK activity produced by PMA, but the effect of EGF in this regard is potentiated. We conclude that PKC and EGF act through parallel pathways to stimulate ERK phosphorylation and activity. The inhibitor studies, in addition, indicate that activation of PKC may moderate the actions of the EGF pathway via a tonic inhibitory feedback. PMID- 7860644 TI - Receptor binding of PDGF-AA and PDGF-BB, and the modulation of PDGF receptors by TGF-beta, in human periodontal ligament cells. AB - The growth factors PDGF-AA and PDGF-BB have previously been shown to be potent mitogens for human periodontal ligament (hPDL) cells in vitro. Additionally, the mitogenic response to PDGF-AA has been shown to be specifically inhibited by TGF beta. The purpose of the present investigation was to examine the binding of PDGF AA and PDGF-BB, and the modulation of PDGF binding by TGF-beta, in hPDL cells. Scatchard analysis identified an average of 32,000 PDGF-AA high-affinity binding sites per cell with a dissociation constant (Kd) of 0.66 nM and an average of 36,000 PDGF-BB binding sites per cell with a dissociation constant (kd) of 0.44 nM. After treatment with TGF-beta, the receptor number for PDGF-AA was found to specifically decrease by approximately 50%, with no change in binding affinity. This reduced number of binding sites was shown to correlate with both a decrease in levels of receptor tyrosine phosphorylation and a decreased number of alpha receptor subunits. Northern blot analysis identified the TGF-beta-mediated decrease in PDGF alpha receptor subunit mRNA levels. PDGF-BB showed little change in the number of binding sites or in the binding affinity with TGF-beta treatment, and the data were consistent with an increase in the number of beta receptor subunits. These results demonstrate nearly equivalent numbers of receptors for both PDGF-AA and PDGF-BB in hPDL cells. Also, modulation of PDGF binding, by TGF-beta, was shown to result in a reduced number of alpha receptor subunits with an increase in the number of beta receptor subunits. PMID- 7860645 TI - Zinc inhibits turnover of labile mRNAs in intact cells. AB - For immediate early genes such as the c-fos proto-oncogene, mRNA breakdown is very rapid and is largely responsible for the transient nature of mRNA accumulation after transcription is stimulated. We found that in several types of cultured cells and in mice, Zn++ caused marked accumulation of c-fos mRNA and that of another labile mRNA, that encoding the tristetraprolin (TTP) protein. Exposure of TK-L cells to 100 microM ZnSO4 caused an increase of c-fos and TTP mRNA levels within 1 h that reached peak levels in 4-8 h and remained constant to 12 h. Increases in fos protein accumulation were also noted. When the cells were exposed to Zn++ for 4 h and then exposed to actinomycin D, both c-fos and TTP mRNA levels remained constant for up to 10 h, indicating that Zn++ was preventing the breakdown of both c-fos and TTP mRNA. Also, 100 microM ZnSO4 inhibited protein synthesis in TK-L cells, suggesting that the effect on mRNA accumulation could have been an indirect effect resulting from inhibited protein synthesis. Zn++ was unable to inhibit the breakdown of TTP and c-fos mRNA in vitro; however, extracts from cells exposed to Zn++ were less able to cause the breakdown of TTP and c-fos mRNAs than were extracts from control cells, again suggesting that Zn++ indirectly affects mRNA stability through inhibition of protein synthesis. These studies suggest that in addition to their effects on gene transcription, Zn++ and other divalent cations may regulate gene expression by affecting mRNA stability. PMID- 7860646 TI - Quantitative export of FGF-2 occurs through an alternative, energy-dependent, non ER/Golgi pathway. AB - Although basic fibroblast growth factor (bFGF/FGF-2) is found outside cells, it lacks a conventional signal peptide sequence; the mechanism underlying its export from cells is therefore unknown. Using a transient COS-1 cell expression system, we have identified a novel membrane-associated transport pathway that mediates export of FGF-2. This export pathway is specific for the 18-kD isoform of FGF-2, is resistant to the anti-Golgi effects of Brefeldin A, and is energy-dependent. In FGF-2-transfected COS-1 cells, this ER/Golgi-independent pathway appears to be constitutively active and functions to quantitatively export metabolically labeled 18-kD FGF-2. Co-transfection and co-immunoprecipitation experiments, using a vector encoding the cytoplasmic protein neomycin phosphotransferase, further demonstrated the selectivity of this export pathway for FGF-2. When neomycin phosphotransferase was appended to the COOH-terminus of 18-kD FGF-2, the chimera was exported. However, the transmembrane anchor sequence of the integral membrane glycoprotein (G protein) of vesicular stomatitis virus (VSV) blocked export. The chimeric protein localized to the plasma membrane with its FGF-2 domain extracellular and remained cell-associated following alkaline carbonate extraction. Taken together, the data suggest that FGF-2 is "exported" from cells via a unique cellular pathway, which is clearly distinct from classical signal peptide-mediated secretion. This model system provides a basis for the development and testing of therapeutic agents which may block FGF-2 export. Such an intervention may be of considerable use for the treatment of angiogenesis dependent diseases involving FGF-2. PMID- 7860647 TI - Transcriptional and posttranscriptional regulation of urokinase-type plasminogen activator expression in endothelial cells by basic fibroblast growth factor. AB - The mechanism of induction of urokinase-type plasminogen activator (uPA) by basic fibroblast growth factor (bFGF) was explored in fetal bovine aortic endothelial GM 7373 cells. A three- to four-fold increase in the steady-state levels of uPA mRNA was observed after 6 h of incubation of the cell cultures with bFGF. Accordingly, nuclear run-on experiments showed a 2-2.4-fold increase in the rate of uPA gene transcription during the first 4 h of treatment with the growth factor. bFGF did not affect uPA mRNA stability, as evaluated by chase experiments with the mRNA synthesis inhibitor actinomycin D. Upregulation of uPA mRNA was followed by a delayed increase in uPA protein synthesis paralleled by an increase in secreted and cell-associated uPA activity. Twelve h were required before accumulated uPA mRNA was translated into the corresponding protein. During this time interval, the continuous presence of biologically active bFGF in the extracellular environment represented an absolute requirement for uPA mRNA translation. Substitution of residues Lys-27, Lys-30, and Arg-31 to glutamine residues in the bFGF molecule resulted in a mutant (M1Q-bFGF) that caused uPA mRNA accumulation in the absence of a significant increase in cell-associated uPA activity. M1Q-bFGF also induced an increase in cell-associated uPA activity only when added to the cell cultures in the presence of soluble heparin. These results provide evidence that bFGF can affect uPA expression in endothelial GM 7373 cells both at transcriptional and posttranscriptional translational levels. They also show the possibility to dissociate upregulation of uPA mRNA from upregulation of uPA activity by mutagenesis of the bFGF molecule. PMID- 7860648 TI - Betamethasone activation of CTP:cholinephosphate cytidylyltransferase is mediated by fatty acids. AB - The purpose of the present study was to determine the mechanisms by which glucocorticoids increase the activity of CTP:cholinephosphate cytidylyltransferase, a key enzyme required for the synthesis of surfactant phosphatidylcholine. Lung cytidylyltransferase exists as an inactive, light form low in lipids (L-form) and an active, heavy form high in lipid content (H-form). In vitro, fatty acids stimulate and aggregate the inactive L-form to the active H form. In vivo, betamethasone increases the amount of H-form while decreasing the amount of L-form in fetal lung. There is also a coordinate increase in total free fatty acids in the H-form. In the present study, we used gas chromatography-mass spectrometry to measure the fatty acid species associated with the H-forms in fetal rat lung after the mothers were treated with betamethasone (1 mg/kg). In vivo, betamethasone increased the total amount of free fatty acids associated with the H-form by 62%. Further, the hormone selectively increased the mass of myristic and oleic acids in H-form by 52 and 82%, respectively. However, betamethasone produced the greatest increase in the amount of H-form linoleic acid, which increased fourfold relative to control. In vitro, each of the fatty acids increased L-form activity in a dose-dependent manner; however, linoleic acid was the most potent. Linoleic and oleic acids also effectively increased L form aggregations. These observations suggest that in vivo glucocorticoids elevate the level of specific fatty acids which convert cytidylyltransferase to the active form. PMID- 7860649 TI - No evidence for a tumor necrosis factor alpha stimulated 2-methylaminoisobutyric acid uptake in hepatocyte monolayer. AB - This study investigates the short-term effects of glucagon and human recombinant tumor necrosis factor alpha (TNF alpha) singly and in association on 2 methylaminoisobutyric acid (MeAIB) transport in hepatocyte monolayers. As expected, glucagon induced a time-dependent stimulation of MeAIB transport. In our experimental conditions, TNF alpha did not induce cytolysis. A 2 hour exposure to TNF alpha (0.05-500 ng/l) with or without glucagon (10(-9) to 10(-6) M) did not modify the basal or glucagon-stimulated MeAIB transport. Varying the duration of exposure to TNF alpha 5 ng/l up to 6 h was equally ineffective. The presence of hydrocortisone potentiated the glucagon-stimulated transport, but TNF alpha remained ineffective. Finally, the association of interferon (IFN gamma) with TNF alpha and/or glucagon was unable to modify the transport activity. These data demonstrate that TNF alpha does not exert a direct effect on MeAIB transport in hepatocytes, at least on a short-term basis. PMID- 7860650 TI - Cytoplasmic juxtamembrane domain of the human EGF receptor is required for basolateral localization in MDCK cells. AB - Although it is well established that epidermal growth factor receptors (EGFRs) are asymmetrically expressed at the basolateral plasma membrane in polarized epithelial cells, how this process is regulated is not known. The purpose of this study was to address the mechanism of directed EGFR basolateral sorting using the Madin-Darby canine kidney (MDCK) cell model. The first set of experiments established sorting patterns for endogenous canine EGFRs. The polarity of the canine EGFR was not quantitatively affected by differences in electrical resistance exhibited by the MDCK I and MDCK II cell strains. In both cases, greater than 90% of total surface EGFRs was localized to the basolateral surface. Canine EGFRs sort directly to the basolateral membrane from the trans-Golgi network with a half-time of approximately 45 min and have an approximate t1/2 of 12.5 h once reaching the basolateral surface. Human holoreceptors expressed in stably transfected MDCK cells also localize to the basolateral membrane with similar efficiency. To identify EGFR sequences necessary for basolateral sorting, MDCK cells were transfected with cDNAs coding for cytoplasmically truncated human receptor proteins. Human EGFRs truncated at Arg-651 were localized predominantly at the apical surface of filter-grown cells, whereas receptors truncated at Leu 723 were predominantly basolateral. These results suggest that the cytoplasmic juxtamembrane domain contains a positive basolateral sorting determinant. Moreover, the EGFR ectodomain or transmembrane domain may possess a cryptic sequence that specifically interacts with the apical sorting machinery once the dominant basolateral sorting signal is removed. Further elucidation of the precise location of these signals will enhance our basic understanding of regulated plasma membrane sorting, as well as the functional consequences of inappropriate EGFR expression associated with certain pathophysiologic and malignant states. PMID- 7860651 TI - Spreading waves of a reduced diffusion coefficient of water in normal and ischemic rat brain. AB - Using echo planar diffusion-weighted magnetic resonance imaging, we measured three-dimensional changes in the apparent diffusion coefficient (ADC) of water in eight contiguous coronal slices, encompassing the entire rat brain, before and after local cortical stimulation. We applied chemical (potassium chloride application; n = 6) and mechanical (needle stab; n = 4) stimulations to the right posterior parietal rat cortex. In all animals in which potassium chloride or the needle stab was applied, a region of decreased ADC values to a mean of 0.45 +/- 0.03 x 10(-5)cm2/s occurred. These reduced ADC levels appeared in the posterior parietal cortex within 1 min after cortical stimulation and the change recovered within 1 min. Then a ripple-like movement of similar changes developed across the unilateral cortex. This change was localized to the cortex and no significant ADC changes occurred in subcortical structures. The propagating speed of this movement was 3.4 +/- 0.5 mm/min. These findings are compatible with spreading depression as observed electrophysiologically. Similar ADC changes occurred in areas distinct from the ischemic lesion in 3 of 12 animals subjected to focal cerebral ischemia. This magnetic resonance method could detect spreading ADC decline if it occurred in human diseases including brain ischemia. PMID- 7860652 TI - In vivo models of cerebral ischemia: effects of parenterally administered NMDA receptor glycine site antagonists. AB - Both in vitro and in vivo experiments have implicated extracellular glycine in the pathogenesis of ischemic brain damage. Recently, halogenated derivatives of quinoxaline-2,3-dione have been synthesized that possess bioavailability when parenterally administered and minimal psychotomimetic properties. Such compounds have allowed investigation into the efficacy of glycine receptor antagonism as a strategy for protection against cerebral ischemic insults. Rats underwent either 90 min of middle cerebral artery filament occlusion or 10 min of forebrain ischemia with recovery while receiving intraperitoneal injections of either a glycine receptor antagonist (ACEA-1021, ACEA-1031, or ACEA-1011) or vehicle (dimethyl sulfoxide). Both ACEA-1021 and ACEA-1031 reduced cerebral infarct volumes and were associated with a reduced incidence of hemiparesis resulting from MCA occlusion. ACEA-1011, administered in a smaller dose had no effect. In the forebrain ischemia model, glycine receptor antagonism had no effect on delayed neuronal necrosis in the hippocampal CA1 sector, neocortex, or caudoputamen. We conclude that pharmacologic antagonism of glycine at the strychnine-insensitive glycine receptor presents a neuroprotective profile similar to that previously observed for antagonists of glutamate at the N-methyl D-aspartate complex with a potential for fewer side effects. PMID- 7860653 TI - The neuroprotective effect of the glycine site antagonist 3R-(+)-cis-4-methyl HA966 (L-687,414) in a rat model of focal ischaemia. AB - 3R-(+)-cis-4-Methyl-HA966 (L-687,414) is a novel and selective, low intrinsic activity, partial agonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor. Thus, while it acts primarily to block NMDA receptor function in the presence of glycine, it fails to produce a complete block of NMDA receptor activation. In this study, we have investigated its neuroprotective effects in a rat model of focal ischaemia, involving permanent occlusion of the left middle cerebral artery. L-687,414 was administered as a bolus dose of 17.6 mg/kg i.v. straight after the occlusion or as a bolus dose + infusion for 4 h. The doses of L-687,414 used for the infusion studies were 7 mg/kg i.v. + 7 mg/kg/h, 14 mg/kg + 14 mg/kg/h, or 30 mg/kg + 30 mg/kg/h. The 17.6-mg/kg dose gave an estimated peak plasma level of 24 micrograms/ml, which decayed with a t1/2 of 56 min. The three infusion dosing regimens gave mean plasma levels over the 4 h of 11, 25 and 61 micrograms/ml plasma, respectively. The 17.6-mg/kg dose of L-687,414 gave no significant protection against the volume of hemispheric, cortical, or caudate damage when compared with the control group of animals. The lowest infusion dosing regimen of L-687,414 which gave a plasma level of 11 micrograms/ml over the 4 h was also ineffective against the volume of infarction measured in the different brain regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7860654 TI - Reexpression of developmentally regulated MAP2c mRNA after ischemia: colocalization with hsp72 mRNA in vulnerable neurons. AB - Levels of mRNAs encoding the microtubule-associated proteins MAP2b and MAP2c as well as the 70-kDa stress protein [72-kDa heat shock protein (hsp72)] were evaluated in postischemic rat brain by in situ hybridization with oligonucleotide probes corresponding to the known rat sequences. Rats were subjected to 10-min cardiac arrest, produced by compression of major thoracic vessels, followed by resuscitation. The normally expressed MAP2b mRNA showed transient twofold elevations in all hippocampal neuron populations at 6-h recirculation, followed by a return to control levels by 24 h. MAP2b hybridization was progressively lost thereafter from the vulnerable CA1 and outer cortical layers, preceding both the fall in immunoreactive MAP2b and the eventual cell loss in these regions. The depletion of MAP2b mRNA coincided with an increase in the alternatively spliced MAP2c in vulnerable regions during 12-48 h of recirculation, precisely overlapping the late component of hsp72 expression that persisted in these cell populations. Previous studies have suggested that the initial induction of hsp72 provides an index of potential postischemic injury in neuron populations that may or may not be injured, while lasting hsp72 mRNA expression is associated with cell damage. In contrast, the present results demonstrate that MAP2c expression under these conditions occurs uniquely in neuron populations subject to injury. Available evidence suggests that MAP2c expression represents a plastic response in subpopulations of neurons that will survive in these regions, although it remains to be explicitly determined whether it may also be transiently expressed in dying cells. In any case, these observations demonstrate that reexpression of developmentally regulated MAP2c mRNA is a relatively late postischemic response in vulnerable cell populations, indicating that pathways regulating MAP2 splicing may be closely associated with mechanisms of neuron injury and/or recovery. PMID- 7860655 TI - Regional differences in late-onset iron deposition, ferritin, transferrin, astrocyte proliferation, and microglial activation after transient forebrain ischemia in rat brain. AB - With use of iron histochemistry and immunohistochemistry, regional changes in the appearance of iron, ferritin, transferrin, glial fibrillary acidic protein positive astrocytes, and activated microglia were examined from 1 to 24 weeks after transient forebrain ischemia (four-vessel occlusion model) in rat brain. Expression of the C3bi receptor and the major histocompatibility complex class II antigen was used to identify microglia. Neuronal death was confirmed by hematoxylin-eosin staining only in pyramidal cells of the hippocampal CA1 region, which is known as the area most vulnerable to ischemia. Perls' reaction with 3,3' diaminobenzidine intensification revealed iron deposits in the CA1 region after week 4, which gradually increased and formed clusters by week 24. Iron also deposited in layers III-V of the parietal cortex after week 8 and gradually built up as granular deposits in the cytoplasm of pyramidal cells in frontocortical layer V. An increasing astroglial reaction and the appearance of ferritin immunopositive microglia paralleled the iron accumulation in the hippocampal CA1 region, indicating that iron deposition was probably produced in the process of gliosis. Neither neuronal death nor atrophy was found in the cerebral cortex. Nevertheless, an astroglial and ferritin-immunopositive microglial reaction became evident at week 8 in the parietal cortex. On the other hand, the granular iron deposition in the pyramidal neurons of frontocortical layer V was not accompanied by any glial reaction in the chronic stage of ischemia. Three different types of iron deposition in the chronic phase after transient forebrain ischemia were shown in this study. In view of the neuronal damage caused by iron catalyzed free radical formation, the late-onset iron deposition may be relevant to the pathogenesis of the chronic brain dysfunction seen at a late stage after cerebral ischemia. PMID- 7860656 TI - Ischemia-induced release of amino acids in the hippocampus of aged hypertensive rats. AB - We have recently demonstrated the age-related vulnerability of hippocampal neurons to 20-min forebrain ischemia in spontaneously hypertensive rats (SHR). In the present study, we investigated the effect of aging on the release of amino acids in the hippocampus during transient cerebral ischemia for 20 min. Concentrations of extracellular amino acids and cerebral blood flow in the CA1 subfield were examined by an in vivo brain dialysis technique and a hydrogen clearance method, respectively, in adult (5-7 month) and aged (19-23 month) female SHR. During cerebral ischemia by bilateral carotid artery occlusion, cerebral blood flow to the hippocampus decreased to 20% of the resting values in both groups. After recirculation, both groups showed delayed hypoperfusion which was more prominent in the aged SHR. In the adult rats, concentrations of both aspartate and glutamate increased to approximately 8-fold of the resting values during ischemia. The elevation of these excitatory amino acids in the adult SHR was not significantly different from that in the aged rats. In contrast, the concentration of taurine increased 26-fold in the adult SHR but only 16-fold in the aged rats. Changes in other amino acids were not different between the two groups. These results indicate that an imbalance of excitatory and inhibitory amino acids, e.g., smaller release of taurine, during ischemia may, at least in part, contribute to the age-related vulnerability of hippocampal neurons to transient cerebral ischemia in SHR. PMID- 7860657 TI - Cerebral blood flow and glucose metabolism of the ischemic rim in spontaneously hypertensive stroke-prone rats with occlusion of the middle cerebral artery. AB - To determine acute postischemic metabolic changes of the ischemic rim under conditions of poor collateral circulation, we examined cerebral blood flow and glucose metabolism in the area of the brain around the ischemic tissue in 36 male spontaneously hypertensive stroke-prone rats (SHRSP) in the acute stage of focal ischemia. The right middle cerebral artery (MCA) was occluded dorsal to the rhinal fissure. Four hours after occlusion, local cerebral blood flow (LCBF), glucose content (LCGC), and glucose utilization (LCGU) were measured by quantitative autoradiographic techniques. The lumped constant was determined from the corresponding LCGC. LCBF showed a widespread and marked decrease in the cortex surrounding the ischemic core, in the thalamus, and in the medial portion of the striatum in the MCA-occluded hemisphere, while the lateral segment of the striatum showed an increase of 36%, compared with findings on the contralateral side. LCGC showed little regional variation, but there was an increase of 38% in the zone bordering the ischemic area. LCGU at the cortex surrounding the ischemic core and in the external capsule showed an increase of 55%. The cortex surrounding the ischemic core, the thalamus, and the lateral segment of the striatum in the MCA-occluded hemisphere showed significant decreases in LCGU. It has been speculated that a high accumulation of glucose reflects a demand for glucose for anaerobic glycolysis in the border areas and that such a demand is probably greater in cases of impaired oxygen delivery due to the presence of microcirculatory disturbances in the MCA-occluded SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7860658 TI - In vivo detection of superoxide anion production by the brain using a cytochrome c electrode. AB - A cytochrome c-coated platinized carbon electrode was utilized to detect superoxide generated by the brain during hypoxia/hypercarbia, focal ischemia, and reperfusion and following fluid percussion brain injury with and without hemorrhagic hypotension and reperfusion in the rat. All three of these forms of brain injury were associated with an increase in the superoxide signal. The cytochrome c electrode proved to be sensitive and responsive enough for minute-by minute measurement of superoxide generation by brain tissue. PMID- 7860659 TI - Development of susceptibility to audiogenic seizures following cardiac arrest cerebral ischemia in rats. AB - Susceptibility to audiogenic seizures (AGS) was investigated in Sprague-Dawley rats subjected to cardiac arrest cerebral ischemia (CACI), produced by compression of the major cardiac vessels. The onset of AGS was regularly observed 1 day after CACI of > 5 min duration. The duration of postischemic susceptibility to AGS was directly related to the density of cerebral ischemia, with 50% of more severely ischemic animals still showing AGS susceptibility 8 weeks after CACI. Lesioning of the inferior colliculi (IC) abolished the onset of AGS; no such effect was observed after lesioning the medial geniculate (MG). Glutamic acid decarboxylase (GAD) immunochemistry revealed approximately 50% loss of GAD positive neurons in the IC, which was similar in animals with various durations of AGS susceptibility. Otherwise, there was a conspicuous sprouting of gamma aminobutyric acid (GABA)-ergic terminals in the ventral thalamic nuclei, which peaked approximately 1 month after the CACI. Evaluation of GABA-A inhibitory function in the hippocampus by the paired pulse stimulation revealed changes indicating loss of GABA-A inhibition coinciding with the onset of AGS, and its return in animals tested 2 months after CACI. Our observations suggest a potential role of GABA-ergic dysfunction in the postischemic development of AGS. PMID- 7860660 TI - Mapping of cerebral blood flow changes during audiogenic seizures in Wistar rats: effect of kindling. AB - The quantitative autoradiographic [14C]iodoantipyrine technique was applied to the measurement of rates of local cerebral blood flow (LCBF) during audiogenic seizures in Wistar AS rats belonging to a genetic strain selected at the Centre de Neurochimie (Strasbourg, France) for their sensitivity to sound. Seizures were elicited in native rats never exposed to sound (single audiogenic seizures) or in rats previously exposed to 10-40 seizure-inducing sound stimulations until generalization of the seizure to forebrain areas (referred to as "kindled animals"). During single audiogenic seizures, rates of LCBF increased over control values in all areas but the genu of the corpus callosum. The highest increases in LCBF (180-388%) were recorded in the inferior and superior colliculus, reticular formation, monoaminergic cell groupings, especially the substantia nigra, posterior vegetative nuclei, and many thalamic and hypothalamic regions. The lowest increases were seen in forebrain limbic regions and cortical areas. In kindled animals, LCBF rates increased over control levels in 67 areas of the 75 studied. LCBF increases were generally of a lower amplitude in kindled than in naive rats. Differences between the two groups of seizing rats were located mostly in brain-stem regions, mainly the inferior colliculus, reticular formation, substantia nigra, and posterior vegetative nuclei. Conversely, rates of LCBF were similar in forebrain areas of naive and kindled animals. In conclusion, the present data show that there is a good correlation between the structures known to be involved in the expression of audiogenic seizures (inferior colliculus, reticular formation, substantia nigra mainly) and the large increase in LCBF during single audiogenic seizures, while rates of LCBF increase to a lesser extent in forebrain areas not involved in this type of seizures. The circulatory adaptation to kindled seizures is rather a decreased response in brain-stem regions and no change in the forebrain, although the kindling process induces a generalization of the seizure from brain-stem to anterior regions. PMID- 7860661 TI - Effects of pentylenetetrazol-induced status epilepticus on local cerebral blood flow in the developing rat. AB - The quantitative autoradiographic [14C]-iodoantipyrine technique was applied to measure the effects of a 30-min period of pentylenetetrazol (PTZ)-induced status epilepticus (SE) on local cerebral blood flow (LCBF) in rats 10 (P10), 14 (P14), 17 (P17), and 21 (P21) days after birth. The animals received repetitive, timed injections of subconvulsive doses of PTZ until SE was reached. At P10, SE induced a 32 to 184% increase in the rates of LCBF affecting all structures studied. In P14- and P17 PTZ-treated rats, LCBF values significantly increased in two-thirds of the structures belonging to all systems studied and were not changed by SE in the parietal cortex, dorsal hippocampus, and dentate gyrus. At P21, rates of LCBF were still increased in 48 of the 73 structures studied; however, LCBF values were decreased by SE in most cortical areas, the hippocampus, and the dentate gyrus. CBF and cerebral metabolic rate for glucose (CMRglc) remained coupled in both controls and PTZ-exposed rats. Our results show that changes in LCBF with seizures are age dependent. At the most immature ages, P10 and P14, both LCBF and local CMRglc (LCMRglc) values are largely increased by long-lasting seizures. At P17 and P21, the blood flow response to SE becomes more heterogeneous, with specific decreases in the hippocampus and cortex at P21. The absence of mismatch between LCBF and LCMRglc in PTZ-exposed rats at all ages may explain at least partly why the immature brain is more resistant to seizure-induced brain damage than the adult brain. PMID- 7860662 TI - Quantification of benzodiazepine receptors in human brain using PET, [11C]flumazenil, and a single-experiment protocol. AB - A kinetic method using a multiinjection protocol, positron emission tomography (PET), and [11C]flumazenil as a specific ligand was used to study in vivo the flumazenil-benzodiazepine receptor interactions in the human brain. The model structure is composed of three compartments (plasma, free, and bound ligand) and five parameters (including the benzodiazepine receptor concentration). The arterial plasma concentration, after correction for metabolites, was used as the input function. The experimental protocol, which consisted of three injections of labeled and/or unlabeled ligand, allowed the evaluation of the five model parameters in various brain regions from a single experiment. In particular, the concentration of receptor sites available for binding (B'max) and the equilibrium dissociation constant (KDVR, VR being the volume of reaction) were estimated in five brain regions, including the pons, in which these parameters are identified for the first time (B'max = 4.7 +/- 1.7 pmol/ml and KDVR = 4.4 +/- 1.3 pmol/ml). Due to the large range of measured receptor concentrations, a linear correlation between B'max and KDVR was pointed out (r = 0.88, p < 0.0005) and was interpreted as a linear relationship between B'max and VR, the parameter KD being assumed constant. This result and its concordance with the published data are discussed. Simulation of the usual two-experiment Scatchard analysis, using the pons as a reference region, showed that the bias on the receptor concentration estimates introduced by this method is significant (from 20 to 40%) but can be corrected using an estimate of the receptor concentration in the pons. Furthermore, we propose a new experimental protocol, based on a Scatchard analysis of the PET data obtained with a partial-saturation experiment. This single-injection protocol is entirely noninvasive, and thus the estimation of the benzodiazepine receptor concentration and of the flumazenil affinity is now possible in human patients using a single 1-h experiment without blood sampling. PMID- 7860663 TI - Systemic and cerebral kinetics of 16 alpha [18F]fluoro-17 beta-estradiol: a ligand for the in vivo assessment of estrogen receptor binding parameters. AB - Estrogen receptors are expressed in several brain areas of various animal species, and steroid hormones exert physiologic and biochemical effects on the central nervous system. The aim of the present study was to evaluate in female adult rats, the suitability of 16 alpha [18F]fluoro-17 beta-estradiol ([18F]FES), a selective estrogen receptor ligand, for the in vivo assessment of brain estrogen receptors. This was considered to be a preliminary step in evaluating the potential usefulness of [18F]FES for studies of cerebral estrogen receptors with positron emission tomography (PET) in nonhuman primates and human subjects. We evaluated (a) the time course of the metabolic degradation of [18F]FES in blood; (b) the time course of distribution of the tracer in discrete cerebral areas; (c) the inhibitory effect of increasing doses of cold estradiol on cerebral [18F]FES uptake; and (d) the possibility of in vivo quantification of estrogen receptor binding parameters using both equilibrium and dynamic kinetic analyses. We quantified [18F]FES binding to estrogen receptors using both equilibrium and dynamic kinetic analyses. The results of this study indicate that [18F]FES is a suitable tracer for the measurement of estrogen receptors in the pituitary and hypothalamus, using either the equilibrium or the kinetic analysis. However, [18F]FES is inadequate for the in vivo investigation of estrogen binding sites in brain areas with low receptor density, such as the hippocampus. PMID- 7860664 TI - Simultaneous measurement of cerebral oxygen consumption and blood flow using 17O and 19F magnetic resonance imaging. AB - 17O and 19F magnetic resonance (MR) imaging were used to determine simultaneously the concentrations of H2 17O and CHF3 in 0.8-cc voxels in the cat brain during inhalation of a gas mixture containing both 17O2 and CHF3. The arterial time course of CHF3 was determined by "on-line" mass spectrometer detection of expired CHF3, and the arterial time course of H2 17O was determined by 17O MR analysis of arterial samples withdrawn during the inhalation period. The brain data and the arterial data for the two tracers were combined to calculate the cerebral oxygen consumption (CMRO2) and the CBF. The protocol was repeated on seven cats, using pentobarbital anesthesia. The average values of CMRO2 and CBF for a 0.8-cc voxel in the parietal cortex were 1.5 +/- 0.5 mmol kg-1 min-1 and 38 +/- 15 ml 100 g-1 min-1, respectively. In individual animals the average uncertainty in CMRO2 and CBF, calculated from Monte Carlo approaches, was +/- 9%. PMID- 7860665 TI - Effect of non-steady-state perfusion on xenon-133 cerebral blood flow measurements: an analytical study. AB - Activation studies employing the noninvasive xenon-133 technique are widely used to investigate the cerebral circulation. Typical examples are the investigation of hemispheral specialization of higher cortical function with cognitive activation or the assessment of the hemodynamic reserve in occlusive cerebrovascular disease by CO2 inhalation. Traditionally, in studies using this technique, there is the requirement of a circulatory steady state during the measurement. Due to limitations in the duration of the stimulus or habituation to the stimulus, the basic assumption is often violated. In this study we investigated with the aid of a computer model to what extent blood flow measurement results are affected by non-steady-state blood flow. The findings indicate that cortical activation need not extend throughout the whole measurement to be detectable. Maintenance of activation for at least 5 min is sufficient for a successful measurement. In addition, the results show that the activation should be fully established when the measurement starts to achieve maximal sensitivity. Delay in activating the circulation will result in attenuated responses, especially if the stimulus is delayed beyond 2 min. PMID- 7860666 TI - Regional cerebral blood flow and CO2 reactivity in fulminant hepatic failure. AB - Alterations in cerebral hemodynamics are postulated to contribute to brain herniation, a major cause of death in patients with severe hepatic encephalopathy due to fulminant hepatic failure (FHF). In an effort to identify these changes in cerebral hemodynamics, regional and global cerebral blood flow (CBF) and CO2 reactivity were measured using stable xenon-enhanced computed tomography (Xe/CT) in 24 patients within 72 h of onset of severe hepatic encephalopathy. Regional variations in CBF, most notably, a relative decrease in CBF in the anterior circulation and an increase in CBF in the posterior circulation were found. CBF was significantly lower in FHF patients compared with controls, however, these values are well out of the established ischemic range. FHF patients also showed significant impairment in CBF response to hypoventilation, while the CBF response to hyperventilation remained intact. This study suggests that FHF patients demonstrate early changes in both CBF patterns and CO2 reactivity. The relatively "normal" CBF values obtained in FHF patients in severe hepatic encephalopathy coupled with the lack of vasodilatation to hypoventilation suggest a state of uncoupled CBF and metabolism or "luxury perfusion" that could theoretically contribute to vasogenic edema, brain swelling, and cerebral herniation. PMID- 7860667 TI - Mechanisms of brain ion homeostasis during acute and chronic variations of plasma potassium. AB - Brain and CSF potassium concentrations are well regulated during acute and chronic alterations of plasma potassium. In a previous study, we have shown that during chronic perturbations, regulation is achieved by appropriate adaptation of potassium influx, but that the degree of such adaptation during acute perturbations is much less. To elucidate further potential regulatory mechanisms, rats were rendered acutely or chronically hyper- or hypokalemic (range 2.7-7.6 mM). Measurements were made of brain and CSF water and ion contents to examine whether regulation occurred by modulation of K+ uptake into parenchymal cells. Furthermore, the permeability-surface area products (PSs) of 22Na+ were determined, because changes in K+ efflux fia Na+,K(+)-ATPase on the brain-facing side of the blood-brain barrier might be reflected in modified Na+ permeability. Brain and CSF K+ concentrations and Na PS were all independent of chronic changes in plasma K+ and acute hypokalemia, suggesting that neither modulation of parenchymal K+ uptake nor K+ efflux via the Na+,K(+)-ATPase is involved in extracellular K+ regulation in these conditions. In contrast, Na PSs were increased by 40% (p < 0.05) in acute hyperkalemia. This was accompanied by a slight loss of tissue K+ and water from the intracellular space. These results suggest that increased potassium influx in acute hyperkalemia is compensated by stimulation of K+ efflux via Na+,K(+)-ATPase. A slight degree of overstimulation, as indicated by a net loss of tissue K+, leads us to hypothesize that other factors, apart from the kinetic characteristics of Na+,K(+)-ATPase, may regulate this enzyme at the blood-brain barrier. PMID- 7860669 TI - Effect of hyperglycemia on rCMRglc in rats. PMID- 7860668 TI - The neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427 in focal cerebral ischemia in rats. AB - The present study was carried out to compare the neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427, with that of(+)MK-801 in rat focal cerebral ischemia. Focal cerebral ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). Drugs were administered intraperitoneally immediately after ischemia and once a day for 6 successive days. FR115427 (10 mg/kg, i.p.) significantly improved neurologic deficit at 1 day after ischemia and reduced total infarct volume (54%) at 7 days after ischemia. Although FR115427 (10 mg/kg, s.c.) produced neuronal vacuolization similar to (+)MK-801, FR115427 did not produce adverse effects such as a loss of body weight, mortality, and hypothermia, in contrast to (+)MK-801. These results suggest that FR115427 may be useful in the treatment of stroke. PMID- 7860670 TI - [Evaluation of cholecystectomy by celioscopy. Apropos of a series of 500 operated patients in a general hospital unit]. AB - A series of 500 patients who underwent laparoscopic cholecystectomy is reported. The mean duration of the operation was 46 minutes when completed laparoscopically and 117 minutes when converted to laparotomy. The conversion rate was 10%, and the reoperation rate 2.22%. There were 5 problems related to the bile ducts (1%) including 2 lesions of the common bile duct (0.44%) with only in 21 cases. In one, a stone in the common duct was extracted laparoscopically. Mean hospitalization was 5.5 days. For us, laparoscopic cholecystectomy has become the "gold standard" for the treatment of symptomatic uncomplicated bile stone disease. Reduced hospitalization time should help reduce cost incurred due to the video surgery material. PMID- 7860671 TI - [Place of ampullectomy in the surgical treatment of tumors in Oddi's sphincter]. AB - Ampoulectomy is rarely used for exeresis of tumours of the Oddi ampoula due to the risk of incomplete exeresis and postoperative complications. We performed 10 ampoulectomies between 1981 and 1990 (8 males, and 2 females: mean age 59 years). The operative procedure included wide resection followed by reimplantation of the biliary and pancreatic canals. The operative indications were based on converging evidence proficed by pathological examination of pre- and peroperative biopsies. There were 4 adenomas, 2 villous tumours, 2 ectopic pancreases, 1 somatostatinoma and 1 villous tumour with in situ carcinoma. Post-operative mortality was nil: the only post-operative complication was 1 stress ulcer. In one case, the benign nature of the tumour was infirmed by the pathological examination of the surgical specimen (invasive adenocarcinoma). This patient refused duodenopancreatectomy and died at recurrence 72 months later. For the other patients, mean post operative follow-up was 60 months. Clinical, biological, endoscopic and pathological follow-up have not revealed relapse in any of the other patients. These results show that complete exeresis of benign Oddi tumors can be achieved by ampoulectomy without specific post-operative complications. Progress in echoendoscopy will probably lead to very precise evaluation of the local invasion of these tumours and thus to wider indications and better follow-up in operated patients. PMID- 7860672 TI - [Epicondylitis induced by fluoroquinolones in athletes. Apropos of 2 cases]. AB - Epicondylitis occurred in two leisure athletes who were taking fluoroquinolones. No similar cases have been reported in the literature. In both cases, pain occurred early after initiating drug therapy. Pain was intense and was not controlled by usual care. Echography demonstrated major inflammatory lesions with pseudo-necrosis. Magnetic resonance imaging confirmed the lesions and gave evidence of infraclinical lesions of the adjacent tendons. Surgical disinsertion of the epicondyles with biopsy was indicated due to the persistent pain. Histological examination revealed unspecific lesions of hyalin degeneration and a few giant cells in one case. Pain disappeared after surgery and the patients were able to return to their work, but neither was able to continue his sports activity. Lesions of the Achilles tendon have been observed in patients taking fluoroquinolone and the two cases reported here confirm the possibility of other localizations. Care must therefore be taken when prescribing these antibiotics in patients at risk (dialysis patients, those on corticosteroids, high-performance athletes). PMID- 7860673 TI - [Anorectal traumas by impalement in children. Apropos of 3 cases]. AB - Traumatic impalement is an exceptional cause of anorectal lesions in the child. The clinical diagnosis is sometimes difficult and associated lesions raise the problem of the most appropriate exploratory examination. Based on our experience with three cases, we would emphasize the usefulness of hydrosoluble enema study prudently performed by the surgeon during the preoperative work-up. The precise localization of the lesions must be obtained with careful emergency exploration before repair. Treatment of the trauma includes lavage, drainage and sometimes colostomy. Antibiotics must always be prescribed. Early complications are dominated by infection and long-term sequellae, requiring a long follow-up. PMID- 7860674 TI - [Aorto-esophageal fistula. Apropos of a case]. AB - One case of aortoesophageal fistula is presented. This pathology is rare: most of aortoenteric fistulas are in the duodenojujunum. Clinical presentation is rarely as clear as the Chiari triad describes it: mild thoracic pain, sentinel arterial hemorrhage and exsanguination. Esophagoscopy, computed tomography and arteriography are helpful for diagnosis. Issue is fatal without surgery but patients are often too old to tolerate it. PMID- 7860675 TI - [Ruptures of the tendons of the hand and wrist in rheumatoid arthritis]. AB - We report our experience with 23 patients with rheumatoid arthritis who presented 48 tendon lesions involving 32 extensor tendons and 16 flexion tendons. Translocations of healthy tendons, overlapping with adjacent healthy tendons and tendon grafts were performed. Results for extensor tendons, expressed as defect in residual extension were excellent in 8 patients, good in 5 and mediocre in 4. For flexor tendons, there were 2 excellent results and 5 mediocre results in terms of thumb-palm contact. Prevention by early synovectomy is particularly important. PMID- 7860676 TI - [Abscesses of the spleen. Value of echoguided percutaneous drainage apropos of 4 new cases]. AB - Curative treatment in 4 patients with splenic abscesses was obtained after echoguided percutaneous drainage. An analysis of the literature from 1986 to 1992 revealed that both splenectomy (87 cases) and percutaneous drainage (47 cases) have had their indications. This could appear rather surprising since that in 1986 several reports had already indicated the safety and effectiveness of percutaneous drainage which leads to cure in 70% of the cases and reduces both the cost of the surgical procedure and he long-term risks of splenectomy. The analysis of the recent literature would suggest, with certain reservations related to the nature of this type of analysis, that percutaneous drainage is a superior technique compared with splenectomy. Mortality reported after splenectomy was high (14%) compared with mortality after percutaneous drainage (2%) (1 out of 47 cases). Percutaneous drainage was unsuccessful in 5 patients (11%) who then underwent successful splenectomy. Global cure rate for percutaneous drainage alone was 87%. Based on the results of this analysis of the data in the literature, and on our own personal experience, we conclude that splenectomy should be performed only exceptionally for splenic abscesses, usually in cases with multifocal abscesses or complicated with rupture. PMID- 7860677 TI - [Intestinal intussusception in adults: contribution of ultrasonography]. AB - After observing a benign tumour of the small bowel which led to ileo-ileal invagination in an adult we recalled the main data on the epidemiology, aetiology and diagnosis. In infants, the diagnosis is usually made but in adults, the situation is much rarer and the clinical and radiographic signs are not specific. Echotomography of the abdomen is the most reliable examination. In the adult, surgery is always indicated because invagination is caused by an organic cause in 9 out of 10 cases. PMID- 7860678 TI - [The subscapular combined free flap. Original technique]. AB - Combinations of subscapular pediculated flaps have been used in recent years. These single pedicle flaps include the latissimus dorsi, the serratus, the scapular crest and the ortho and para-scapular skin flaps. Together these flaps comprise a combined subscapular transplant. This combined flap is particularly important since the different components provide great spatial flexibility. Complex and massive pluri-tissular substance losses can thus be reconstructed. We report our work in anatomy and techniques. We found variations in the origin of the subscapular pedicle in 25% of the cases in our anatomy study (50 cases). We recommend dissection of the vascular pedicle via the axillary route first. Thus necessary adaptations can be made as a function of the variations observed. This combined flap can be removed with the patient in supine position. The fact that the position of the patient does not have to change is essential for cervicofacial surgery performed by two teams. The pedicle of the cutaneous scapular flaps is dissected starting ventrally. Since 1990, we have performed 15 combined subscapular transplantations for cervicocephalic reconstructions. PMID- 7860679 TI - [Surgical treatment of esophageal perforations]. AB - Spontaneous and iatrogenic esophageal perforations continue to present life threatening gastroenterologic emergencies. The results in 17 patients being treated between 1986 and 1992 are presented. In respect to localisation of the perforation, the underlying nature of the disease and the condition of the patient an early suture and wrap in all patients with benign diseases and an early esophagectomy in patients with esophageal cancer was aspired. 11 patients having been treated this way survived whereas 3 of six patients with extensive tumour burden and reduced physical state who had been treated conservatively died during the hospital stay. Thus early diagnosis and operative treatment of esophageal perforations improves patients outcome significantly. PMID- 7860680 TI - [Risk and responsibility in celiosurgery]. AB - Not performing laparoscopic surgery is not a dishonour. Likewise, it is not shameful to convert a laparoscopic operation to conventional laparotomy. The mission of the surgical community is to avoid inhibiting progress while assuring patient safety. Based on accepted standards, experts designated by the courts establish a report on the pre, per and postoperative procedures to enlighten the judge who decides on the notion of responsibility in the specific context of laparoscopic surgery. The aim of this work was to inform the practicing surgeon on the known complications, prevention of accidents, the forensic classification and the current estimation of risk. Statistically, laparoscopic surgery is not an accrued risk for insurance companies. Practicians should know that there are specific potential risks involved in this technique which are expressed as a function of the surgeons behaviour before, during and after the operation. Effective training in laparoscopic surgery which reproduces the same action as conventional surgery, but with different procedures, requires, as for conventional surgery regular "fellow" training. The trained, competent, conscientious surgeon can propose the advantages of laparoscopic surgery to his patients while avoiding the disadvantages. PMID- 7860681 TI - [Primary leiomyosarcoma of the femoral vein. Therapeutic aspects]. AB - Leiomyosarcomas are exceptional in peripheral veins. Clinical signs are not specific, secondary to effects of the tumoural mass. Computed tomography and MRI give a precise topographic diagnosis. Pathology examination on biopsy or surgical specimens establishes the histological diagnosis. Therapeutic management must take into account local tumour recurrence and metastasis. Surgical exeresis should be wider than the tumour's pseudocapsule to include micrometastases neighbouring the primary tumour. Post-operative radiotherapy (55 to 70 Gy) and chemotherapy should follow. With this management scheme, local disease is controlled in 85% of the cases with a 5-year follow-up. Local or metastatic extension usually occurs within the first 3 years. Management of venous sarcomas thus requires a multidisciplinary cooperation between the surgeon, the radiotherapists and the chemotherapist. PMID- 7860682 TI - [Our surgical experience in the resection of benign hepatic tumors. Apropos of 31 cases]. AB - The authors report their experience about 31 patients (30 women and 1 man, mean age 45,7 years) opered for a benign hepatic tumor between 1984 and 1993. There were 12 focal nodular hyperplasia, 9 simple hepatic cysts, 8 hemangioma and 1 hepatic adenoma. All but one (a cyst) tumors were completely resected. The reasons of indications for surgery (which is contraversial) are then discussed, most of them being based on doubts concerning correct identification of the tumor (despite a modern assessment by imaging) or symptoms or risks of the tumor. PMID- 7860683 TI - [Predictive factors of recurrence in surgically treated rectal villous tumors. Therapeutic approach based on 184 cases]. AB - The aim of this retrospective study on 184 operated cases was to propose a therapeutic management scheme for villous tumours of the rectum. Among the 184 operated patients, 167 (90,7%), mean age 65 years, were seen after a follow-up of 2 to 20 years. The tumour was most often localized in the rectal ampoula (141 cases) and was benign in 65 p. 100. Endoanal surgery was performed in 76 patients among whom recurrence was observed in 29.7%. Posterior exeresis (Kraske method) was performed in 52 cases with a recurrence rate of 31.9%). Finally, abdominoperineal amputation was performed 20 times, essentially for advanced stage tumours. Based on the statistical analysis of the recurrence factors for these different techniques, we have concluded that endoanal surgery predominates for benign tumours smaller than 5 cm situated at least 8 cm from the anus. Above the size of 5 cm, due to the major risk of tumourectomy, we believe rectal exeresis is the most rational treatment. PMID- 7860684 TI - [Current surgical methods for the etiological diagnosis of mediastinal adenopathies]. AB - The aim of this work was to determine the role of video-thoracoscopy and mediastinoscopy for the diagnosis of lymph node enlargement in the mediastinum of unknown aetiology. From January 1992 to December 1993, 26 patients were seen for surgical biopsy of mediastinal lymph nodes. Relative localization and the requirement for an associated gesture determined the choice between axial mediastinoscopy, parasternal scopy and videothoracoscopy. Mediastinoscopy was performed for peritracheal or right hilar (Barety) nodes and parasternal scopy for anterior mediastinal masses. Videothroacoscopy was performed when the lymph nodes were localized at the preceding sites or when an associated manoeuver was required. Mediastinoscopy was performed in 16 patients. Lymphorrea which subsided after 4 days occurred in one patient and the mean hospital stay was 2.6 days. Diagnosis was achieved in 15 cases. The delay from procedure to treatment was 11 days on the average. Parasternal scopy was used 3 times and gave the diagnosis in all cases. Videothoracoscopy was used for 7 patients including 2 cases with pulmonary biopsies. Diagnosis was established 7 times and the delay to treatment was 12 days. No diagnostic thoracotomie were performed during this period. When access to the mass to be biopsied is difficult with mediastinoscopy (aorto pulmonary, subcarenal, triangular ligament) videothoracotomy can be useful. Post operative follow-up is simple and a specific treatment can be instaured rapidly. Videothoracotomy should be an important supplementary method for mediastinoscopy and helping avoid thoracotomy. PMID- 7860685 TI - [Preliminary results of the evaluation of the Endopatch E-F in digestive surgery]. AB - Endopatch E-F is a new product elaborated with natural human and animal proteins. Its synthesis originates in a covalent link between elastin and fibrin monomers. Numerous experimental studies carried out in animal have previously shown its ability to reinforce healing process of digestive wall. The results reported herein have been obtained in very selected patients in whom a digestive anastomosis had to be done in spite of unfavorable circumstances, such as intra abdominal infection, radiated bowel or ascitis. From October 1990 to October 1992, 21 digestive anastomosis have been performed in 18 patients. All were reinforced by Endopatch E-F. Two deaths have been observed (mortality: 11.1%), which do not look like a consequence of the use of the product (One myocardial infarction and one cirrhotic failure). There were 2 post-operative fistulas (9.5% of the whole anastomosis). No patients had any reaction of intolerance. These preliminary results confirm experimental data, and suggest that Endopatch EF can be used in order to reinforce digestive sutures when performed under unfavorable circumstances. PMID- 7860686 TI - [Under what conditions is laparoscopic treatment of inguinal hernia financially profitable?]. AB - A randomized controlled study between Shouldice technic (119 cases) and laparoscopic totally pre-peritoneal hernia repair (122 cases) was performed to evaluate the different costs. Only with reusable devices, and if the Prolene Mesh is not fixed by stapple, laparoscopic repair, even a specific increasing expenses (700 FF) allow a little benefit (1100 FF per patient). Laparoscopic hernia repair is really benefit for active workers, specially in liberal practice. These conclusion suggest to correlate the technic with professional activity. PMID- 7860687 TI - [Late exterioration of a postoperative cecal fistula in children. Apropos of a rare clinical case]. AB - The authors report a rare clinical observation of a post-appendectomy caecal fistula retardedly exteriorized, in a 18 year old adolescent, managed in the surgical service of the Yaounde General Hospital. The radical treatment was surgical and consisted in right hemicolectomy. Literature was reviewed and therapeutic indications discussed. PMID- 7860688 TI - [Retroperitoneal Castelman disease. Apropos of a new case]. AB - A retroperitoneal localization of Castleman's disease was characterized by angiolymphoid hyperplasia. This rare disease (58 cases of abdominal localization reported to date) raises a question of nosology. The clinical features are not specific. Localized forms in young patients involve deep lymph nodes and have a good prognosis after complete surgical exeresis. Inversely, the clinical picture is much more aggressive in multiple localizations involving preferentially superficial nodes with associated plasmocyte proliferation. The prognosis is mediocre in these forms. Although transition stages have been described due to the lack of any known aetiology, the question of nosology remains open: should the different forms be separated or identified simply as two pathological forms? PMID- 7860689 TI - [Tumors of the digestive muscles. Diagnosis and treatment apropos of 10 cases]. AB - Ten cases of digestive tract muscle tumours emphasized the difficulty in preoperative diagnosis. CT scan gave the best results by visualizing the tumour in all the cases but one. In this case jejunal localization of a small tumour was made by arteriography. In gastric and duodenal localizations, the endoscopic aspect was not particularly specific and too superficial biopsies were always negative. The prognosis depends on pathology results but the distinction between malignancy and benign tumours is not always easy to make. The course of the disease is often needed to correct an erroneous initial diagnosis of benign tumour underscoring the need for careful follow-up. PMID- 7860690 TI - [Complications of colonic diverticulosis and emergency surgery. Prospective study of 56 cases]. AB - Fifty six patients, 26 men (69.7 +/- 11.2 years) and 30 women (77.4 +/- 9.2 years) were admitted in the emergency unit for diverticulosis sigmoiditis. In 75% of cases an other pathology was associated. Excepted 11 extended peritonisis, 7 criterae of operation were required to operate on 17 men and 18 women (mean age = 73.7 +/- 12.5 years) in a delay less than 8 days. Reasons were: 12 occlusive forms, 9 peri-sigmoidis abcedations, 3 hemorrhages. Surgical procedures were: 11 Hartmann procedures, 21 resections with anatomosis of the sigmoid colon with 10 non protected and 3 subtotal colectomy. Postoperative mortality was been 11.4%. The global rate of complications was 28.5 and the mean hospital stay was 18.8 +/- 6.3 days. Application of operative criteriae is usefull to shorter significantly the delay of operation and then the length of evolution of the intraperitoneal infection site. PMID- 7860691 TI - [Incidence and treatment of local recurrences after conservative surgical treatment for cancer of the breast]. AB - Long-term survival is comparable after total mastectomy or conservative surgery for early breast cancer. Our purpose was to evaluate the rate and therapy of breast relapse at the Regional Hospital of Varese (Italy) in a 10 years period. From 1/1/1980 to 31/12/1990 a total of 606 patients with early breast cancer (Stage I or II early) were evaluated. They all were submitted to quadrantectomy, axillary dissection and radiotherapy. In case of metastases to the axillary lymph nodes, hormono or chiotherapy were performed. 425 patients were regularly followed for a period of 2.5-13 years. In 15 patients (3.2%) a local recurrence was discovered. They were treated as follows, 8 patients: mastectomy, 4 patients: conservative surgery, 4 patients: no therapy. The surgical approach of the local recurrence, mastectomy or conservative surgery, does not influence long-term survival of patients treated with conservative surgery and radiotherapy for early stage breast cancer. Conservative surgery is often possible in treating local recurrence without interfering with complete removal of the tumor and long-term survival. PMID- 7860692 TI - [Genetic anomalies of colorectal cancers]. AB - The prognosis of colorectal cancer has been based essentially on pathological data for many years. The analysis of genetic anomalies has led to fundamental progress and clinical advances. Genetic anomalies are routinely studied. 1- Flowcytometry evaluates the quantity of DNA in the nucleus during the cell cycle. 2--Cytogentics is the study of karyotype anomalies by loss or gain of chromosome material and structural changes. 3--Molecular biology gives a means of recognizing chromosome losses and especially to study oncogenic or antioncogenic mutations. These analyses allow: 1--an evaluation of their value as a prognosis factor and thus their use for indicating adjuvant medical and/or surgical treatments. 2--an understanding of cancerogenic processes. 3--the development of future therapeutic techniques based on a better understanding of the mechanisms involved. 4--familial counselling in high risk families and an examination of responsible or favouring genes in certain familial cancers. Research into familial forms has recently led led to the demonstration of genetic alterations located on chromosomes 1 and 2. These anomalies called RER correspond to alterations found on tumors. Studying these alterations will allow better prediction of high risk subjects in cancer families without polyposis. PMID- 7860693 TI - [Experience in the treatment of large eventrations of the lateral abdominal wall according to a new method]. PMID- 7860694 TI - [Advantages and disadvantages of ambulatory surgery]. PMID- 7860695 TI - [Liver abscess revealing adenocarcinoma of the right colon]. PMID- 7860696 TI - [Volvulus of the gallbladder in adults: apropos of a case]. PMID- 7860697 TI - [Omentocele in abdominal wounds by knife stab]. PMID- 7860698 TI - Extraction of junctional complexes from triad junctions of rabbit skeletal muscle. AB - Triadin in skeletal muscle exists as a disulfide linked oligomer. It does not dissolve well in CHAPS detergent even in 1 M KCl, but is solubilized after reduction to its monomer by the addition of 2-mercaptoethanol. Purified reduced triadin is not retained on a hydroxylapatite column in the presence of 30 mM Potassium phosphate, while the junctional foot protein and dihydropyridine receptor purified in the absence of triadin are both retained. In contrast, triadin solubilized as a detergent extract of reduced triadic vesicles is retained by the hydroxylapatite column and elutes concomitantly with the junctional foot protein and dihydropyridine receptor. These findings contrast with the observation that native non-reduced triadin is tightly bound to hydroxylapatite and can be separated from the dihydropyridine receptor and the junctional foot protein with elevated potassium phosphate concentrations. Triadin derived from a detergent extract of reduced vesicles is retained with the hydroxytapatite column in the presence of 180 mM potassium phosphate (0 KCl) which eluted a portion of the junctional foot protein and dihydropyridine receptor. Triadin can then be eluted with the remaining portion of junctional foot protein and dihydropyridine receptor upon the addition of KCl (820 mM) to the 180 mM potassium phosphate medium. Gel electrophoresis confirmed the enrichment of junctional proteins in the 180 mM KPi/820 mM KCl eluate. Rate zonal centrifugation of the 180 mM KPi/820 mM KCl eluate shows that a portion of triadin co-migrates with the dihydropyridine receptor indicative of a much higher molecular weight entity than monomeric triadin. Triadin and the dihydropyridine receptor were, however, separated from the junctional foot protein on rate zonal centrifugation. The dissociated proteins of the complex elute from hydroxylapatite columns similar to the purified proteins. Triadin in the high salt hydroxylapatite extract could also be immunoprecipitated by a monoclonal antibody to the junctional foot protein. Furthermore, the dihydropyridine receptor is immunoprecipitated by a monoclonal antibody directed against triadin providing another indication of a complex between the three proteins. Collectively, these results demonstrate a role for triadin as the linkage between the junctional foot protein and dihydropyridine receptor creating a ternary complex at the triad junction in skeletal muscle. PMID- 7860699 TI - Identification of alpha-cardiac myosin heavy chain mRNA and protein in extraocular muscle of the adult rabbit. AB - Extraocular muscles contain both fast-twitch and multiply-innervated, tonic contracting fibres. In rat, these fibres collectively express numerous myosin heavy chain isoforms including fast-type embryonic and neonatal, adult slow twitch type I and fast twitch type II, and a fast isoform unique to extraocular muscle. Immunocytochemical and Western blotting results are presented which suggest that, in rabbit, an additional species, the alpha-cardiac myosin heavy chain, is present. The immunoreactive species is found in all rabbit extraocular muscles and in the extraocular muscles is expressed in almost all fibres which do not contain a fast myosin heavy chain. Positive identification of this isoform as the alpha-cardiac myosin heavy chain was obtained by sequencing a cloned PCR product derived from extraocular muscle mRNA unique to the 3'-end of rabbit alpha cardiac myosin heavy chain mRNA. This is the first unequivocal demonstration of alpha-cardiac myosin heavy chain expression in extraocular muscle. PMID- 7860700 TI - Differences in myosin composition between human oro-facial, masticatory and limb muscles: enzyme-, immunohisto- and biochemical studies. AB - Immunohistochemistry was used to determine the myosin composition of defined fibre types of three embryologically different adult muscles, the oro-facial, masseter and limb muscles. In addition, the myosin composition in whole muscle specimens was analysed with biochemical methods. Both similarities and differences between muscles in the content of myosin heavy chains and myosin light chains were found. Nevertheless, each muscle had its own distinct identity. Our results indicated the presence of a previously undetected fast myosin heavy chain isoform in the oro-facial type II fibre population, tentatively termed 'fast F'. The masseter contained aberrant myosin isoforms, such as foetal myosin heavy chain and alpha-cardiac myosin heavy chain and unique combinations of myosin heavy chain isoforms which were not found in the limb or oro-facial muscles. The type IM and IIC fibres coexpressed slow and fast A myosin heavy chains in the oro-facial and limb muscles but slow and a fast B like myosin heavy chain in the masseter. While single oro-facial and limb muscle fibres contained one or two myosin heavy chain types, single masseter fibres coexpressed up to four different myosin heavy chain isoforms. Describing the fibres according to their expression of myosin heavy chain isozymes, up to five fibre types could be distinguished in the oro-facial and limb muscles and eight in the masseter. Oro facial and limb muscles expressed five myosin light chains, MLC1S, MLC2S, MLC1F, MLC2F and MLC3F, and the masseter four, MLC1S, MLC2S, MLC1F, and, in addition, an embryonic myosin light chain, MLC1emb, which is usually not present in normal adult skeletal muscle. These results probably reflect the way the muscles have evolved to meet the specialized functional requirements imposed upon them and are in agreement with the previously proposed concept that jaw and limb muscles belong to two distinct allotypes. PMID- 7860701 TI - Non-uniformity of sarcomere lengths can explain the 'catch-like' effect of arthropod muscle. AB - The 'catch-like' effect, a hysteresis phenomenon in arthropod skeletal muscle contraction thought to be related to the catch of molluscan smooth muscle, was investigated in the closer muscle of the crab Eriphia spinifrons. Several parameters were varied to determine their influence on the catch-like effect. These parameters were (1) the frequency of repetitive stimulation of the slow excitatory neuron, (2) additional stimulation of the inhibitory neuron, (3) the amount of stretch applied to the muscle and (4) the stiffness of the mechano electrical transducer. The results show that the catch-like effect is not related to the catch of molluscan smooth muscle but rather to the 'residual force enhancement' or 'creep' phenomenon described for vertebrate muscle. A hypothesis for residual force enhancement implies that the increase in force is caused by non-uniformity of sarcomere lengths along the muscle fibre. Based on this hypothesis and the actual force-length relationship of the crab muscle studied, calculations were carried out to determine, if the observed catch-like effect can be explained by such a model. The calculations corroborate the experimental evidence. The catch-like effect of arthropod muscles can thus be explained by the same mechanism responsible for residual force enhancement and creep in vertebrate muscle. A physiological relevance of the catch-like effect in arthropod muscle is inferred. PMID- 7860702 TI - Regulatory domains of myosins: influence of heavy chain on Ca(2+)-binding. AB - Light chain binding domains of rabbit skeletal, turkey gizzard and scallop myosin comprised of equimolar amounts of a short heavy chain fragment, essential light chain, and regulatory light chain have been obtained following extensive tryptic digestion. These complexes that are analogous to the regulatory domain prepared previously from scallop myosin by digestion with clostripain resist proteolysis due to the mutual protection of the heavy chain and the light chains, and are common structural features of the myosins studied. Specific Ca(2+)-binding by the regulatory domains reflects the behaviour of intact myosin; only scallop regulatory domain has a specific Ca(2+)-binding site. The heavy chain fragments of the different regulatory domains have been isolated under denaturing conditions and reconstituted with scallop essential light chain and scallop regulatory light chain or turkey gizzard regulatory light chain to yield regulatory domain hybrids. Hybrids containing the turkey gizzard regulatory light chain were used in Ca(2+)-binding studies since they were far more stable than their counterparts with the scallop regulatory light chain. The gizzard hybrid binds Ca2+ with a comparable specificity but somewhat lower affinity than native scallop regulatory domain. The rabbit regulatory domain hybrid also binds Ca2+, although with a reduced affinity and specificity. The results indicate that Ca(2+)-binding ability is determined by the light chains and modified by the heavy chains. PMID- 7860703 TI - Myosin filament ATPase is enhanced by intramolecularly cross-linked actin. AB - Reaction of rabbit skeletal muscle F-actin with the lysine-directed photolabile cross-linker, N-5-azido-2-nitrobenzoyloxy succinimide was limited to Lysine-328 and Lysine-326, with Lysine-328 being labelled to a greater extent. Photolysis of the modified actin enhanced the actin-activated MgATPase activity of filamentous scallop myosin 3-4-fold more than unmodified actin, without affecting calcium sensitivity. Unphotolysed modified actin behaved as untreated actin, indicating that photolysis was essential for the effect. The actin-activated ATPase of filamentous rabbit myosin was similarly increased by photolysed N-5-azido-2 nitrobenzoyloxy succinimide-modified actin. After photolysis in either the monomeric (G-) or filamentous (F-) form, N-5-azido-2-nitrobenzoyloxy succinimide modified actin moved as a monomeric (42 kDa) species on SDS gels, and depolymerized and polymerized readily, demonstrating that any cross-linking event produced by photolysis must be intramolecular. In contrast to the substantial increase in actin-activated ATPase activity observed when photolysed ANB-NOS modified actin was added to filamentous myosin, the enhancement was not observed with the soluble HMM and S-1 fragments of myosin. Photolysed modified actin showed only poor movement on a rabbit HMM-coated surface in vitro motility assays. These results can be explained if the internally cross-linked G-actin subunits which comprise only a fraction of the actin population, either weaken the actin-actin contacts or have an increased affinity for myosin. PMID- 7860704 TI - The effects of chloride ions in excitation-contraction coupling and sarcoplasmic reticulum calcium release in twitch muscle fibre. AB - Using the sucrose vaseline gap technique, experiments were carried out on isolated frog twitch muscle fibre to investigate the role of chloride ions in excitation-contraction coupling. In current clamp conditions, replacement of chloride ions by impermeant anions led to an increase of the amplitude of the early after potential and of the amplitude of the twitch. Addition of a chloride channel blocker, anthracene-9-carboxylic acid gave similar results. In voltage clamp conditions, replacement of chloride ions by impermeant anions induced a decrease of the outward current and an increase of both the amplitude of the contraction and of the resting tension. Addition of anthracene-9-carboxylic acid gave similar results except that resting tension was not modified. Replacement of chloride ions by impermeant anions resulted in a shift of the tension-voltage relationship toward negative potentials and in an increase of the amplitude of the contraction at all potentials. Outward currents were also reduced at all potentials but no shift of the current-voltage relationship was observed. Similar results were obtained upon addition of anthracene-9-carboxylic acid. Rapid filtration experiments were performed on isolated sarcoplasmic reticulum vesicles to study the role of chloride ions in Ca2+ release. Under conditions where KCl was present in the intra- and extravesicular media, removal of chloride ions from the release solution produced a 2-fold increase in the rate of Ca(2+)-induced Ca2+ release. Together, these results suggest that, besides their involvement in the action potential time course, chloride ions could exert a negative control on the sarcoplasmic reticulum Ca2+ release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7860705 TI - Nerve-dependent recovery of metabolic pathways in regenerating soleus muscles. AB - The metabolic recovery potential of muscle was studied in regenerating soleus muscles of young adult rats. Degeneration was induced by subfascial injection of a myotoxic snake venom. After regeneration for selected periods up to 2 weeks, samples of whole muscle were analysed for hexokinase (EC 2.7.1.1), phosphofructokinase (EC 2.7.1.11), lactate dehydrogenase (EC 1.1.11.27), adenylokinase (EC 2.7.4.3), creatine kinase (EC 2.7.3.2), malate dehydrogenase (EC 1.1.11.37), citrate synthase (EC 4.1.3.7) and beta-hydroxyacyl CoA dehydrogenase (EC 1.1.1.35). Lactate dehydrogenase, adenylokinase, malate dehydrogenase and beta-hydroxyacyl CoA dehydrogenase were also measured in individual fibres of muscle regenerating up to 4 weeks. We found that in the presence of nerve there was complete recovery of muscle metabolic capacity. However, there were differences in the rate of recovery of the activity of enzymes belonging to different energy-generating pathways. Lactate dehydrogenase, an enzyme representing glycolytic metabolism, reached normal activity immediately upon myofibre formation, only 3 days after venom injection, while oxidative enzymes required a week or more to reach normal activity levels. The delay in oxidative enzyme recovery coincided with physiological parameters of reinnervation. Therefore, to further test the role of nerve on the metabolic recovery process, muscle regeneration was studied following venom-induced degeneration coupled with denervation. In the absence of innervation, most enzymes failed to recover to normal activity levels. Lactate dehydrogenase was the only enzyme to achieve normal levels, and it did so as rapidly as in innervated-regenerating soleus muscles. The remainder of the glycolytic enzymes and the high energy phosphate enzymes recovered only partially. Oxidative enzymes showed no recovery and were severely reduced in the absence of reinnervation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7860706 TI - Muscle biology workshop, 35th annual Drosophila research conference. PMID- 7860707 TI - T cells with encephalitogenic potential from multiple sclerosis patients and Lewis rats fail to induce disease in SCID mice following intracisternal injection. AB - Intracisternal (IC) transfer of cerebrospinal fluid (CSF) mononuclear cells from multiple sclerosis (MS) patients has been reported by others to induce an 'MS like pathology' in severe combined immunodeficient (SCID) mice. We injected cells from several sources intracisternally into SCID mice and assessed the recipients for clinical and histological disease. CSF cells and myelin basic protein (BP) specific T lymphocytes from MS patients failed to induce clinical or histological disease following IC injection in SCID mice. Similarly, encephalitogenic BP specific T cells from Lewis rats were unable to induce disease after IC injection in either SCID mice or Lewis rats, even at cell numbers which induced experimental autoimmune encephalomyelitis in Lewis rats following intraperitoneal (IP) injection. In contrast, naive Lewis rat splenocytes, which were capable of inducing lethal graft-versus-host (GVH) disease following IP transfer in SCID mice, induced paralysis and histopathological changes following IC transfer in SCID mice. We conclude that MS CSF cells do not typically transfer disease into SCID mice following IC injection. Furthermore, it appears likely that neuropathological disease following IC transfer of cells reflects the potential of the transferred cells for inducing GVH disease. Specific recognition of neuroantigens by T cells, as occurs in EAE, is probably not involved in the transfer of paralytic disease by IC transferred MS patient CSF cells. PMID- 7860708 TI - Expression of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 after focal cerebral ischemia in the rat. AB - Chemoattractant cytokines, the chemokines, play an important role in early events of inflammation at the site of tissue damage. We examined the expression of mRNA and the protein products of two such chemokines; i.e. monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the ischemic brain tissue following middle cerebral artery occlusion (MCAo). The mRNA transcripts of MCP-1 and MIP-1 alpha were detected by Northern hybridization and reverse transcriptase polymerase chain reaction (RT/PCR), respectively, and the anatomic distribution of specific proteins was analyzed by immunohistochemistry. We found that MCP-1 mRNA was not expressed in the brains of normal rats or rats sacrificed 2 h after MCAo. 6 h after the induction of cerebral ischemia, weak expression of both mRNAs was detected in the ischemic tissue. mRNAs were expressed up to 48 h, and were markedly attenuated at 96 h. In the rats subjected to MCA occlusion, MCP-1 immunoreactivity was diffusely expressed and localized to the ischemic area, and was most intense at 48 h after MCA occlusion. Endothelial cells and macrophage-like cells expressed MCP-1 protein in the ischemic brain. The distribution and morphology of MIP-1 alpha immunoreactive cells were identical with activated astrocytes. We conclude that MCP-1 and MIP-1 alpha mRNAs and proteins are induced after cerebral ischemia in the rat. They may have a role in promoting inflammatory and/or repair processes in the ischemic brain, possibly by attracting or modulating inflammatory cells in the ischemic area. PMID- 7860709 TI - Prevention of chronic relapsing experimental autoimmune encephalomyelitis by soluble tumor necrosis factor receptor I. AB - We have evaluated the effect of the type I (p-55, type beta) soluble tumor necrosis factor receptor (sTNFrI) in an animal model of multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) was induced in SJL/J mice by adoptive transfer of T lymphocytes sensitized to myelin basic protein (MBP). sTNFrI completely blocked both clinical signs of disease and pathological changes that included CNS demyelination and inflammatory cell infiltration. Effective inhibition of disease expression was obtained using several different regimens of subcutaneous (s.c.) injection. These included daily doses starting at day 0, every other day injections starting at day 0, daily doses starting on day 4, and two doses separated by 12 h on day 1 and 2. Furthermore, treatment with sTNFrI for 15 days completely protected these animals from the recurrent episodes of disease normally associated with adoptively transferred EAE. These findings suggest that TNF plays a major causative role in EAE and that the sTNFrI may prove to be a useful therapeutic approach in multiple sclerosis. PMID- 7860710 TI - Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. AB - To demonstrate the influence of n-3 PUFA supplementation on cytokine and eicosanoid production in peripheral blood mononuclear cells (PBMCs) of MS patients (MSP), we investigated the impact of a 6-month dietary supplementation with these fatty acids on the levels of interleukin-1 beta (IL-1 beta), IL-2, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the supernatants of stimulated PBMCs and serum soluble IL-2 receptors in a group of 20 relapsing-remitting (R-R) MSP and a group of 15 age-matched control individuals (CI). The production of PGE2 and LTB4 in the stimulated PBMCs was also assessed in patient and control groups supplemented with n-3 PUFAs. In both groups, n-3 PUFA supplementation led to a significant decrease in the levels of IL-1 beta and TNF-alpha, and this reduction was more pronounced in the 3rd and 6th month of supplementation. An analogous decrease was observed in the levels of IL-2 and IFN-gamma produced by stimulated PBMCs, and in the levels of serum soluble IL-2 receptors. n-3 PUFA supplementation also appeared to significantly affect prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production in PBMCs, both in MSP and the control group. The reduced production of these proinflammatory eicosanoids, and the decrease of some cytokines with an immunohenancing effect as a consequence of n-3 PUFA supplementation, could modulate some immune functions which have been demonstrated to be altered in MSP. PMID- 7860711 TI - Dopamine D1-like receptors in the thymus of aged rats: a radioligand binding and autoradiographic study. AB - Age-dependent changes in the density and pattern of dopamine D1-like receptors were studied in the thymus of young (3 months), adult (12 months) and aged (24 months) male Wistar rats using combined radioligand binding and autoradiographic techniques. [3H]SCH 23390, which was used as a ligand, was specifically bound to sections of the thymus in a manner consistent with the labelling of dopamine D5 receptor. The dissociation constant value was similar in the thymus of the three animal groups examined. The maximal density of binding sites, evaluated with conventional radioligand binding techniques, was significantly reduced in the thymus of adult in comparison with young rats and further reduced in aged animals. Silver grains which correspond to [3H]SCH 23390 binding sites were revealed by light microscope autoradiography primarily in the cortex of the thymus and in lesser amounts within thymic corpuscles. A progressive decrease in the density of silver grains more pronounced in the cortex than in thymic corpuscles was observed in the thymus of adult and old in comparison with young rats. The loss of silver grains revealed with autoradiography is more moderate than the decrease in the density of binding sites shown by radioligand binding. Silver grains developed per single cells (probably lymphocytes) of the thymic cortex were reduced between young and adult rats and further decreased in old rats. The above findings suggest that the age-related decline in the density of dopamine D5 receptor assayed in the thymus is due in part to the reduced thymic mass with aging.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7860712 TI - The subarachnoid space as a site for precursor T cell proliferation and effector T cell selection in experimental autoimmune encephalomyelitis. AB - To characterize the phenotype of inflammatory cells in the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE), Lewis rats were immunized with guinea pig myelin basic protein and frozen sections of the spinal cord with EAE were examined immunohistochemically using a panel of monoclonal antibodies against T cells and adhesion molecules. In addition, double immunostaining was performed with glial and T cells markers to examine the interaction between infiltrating T cells and reactive brain cells during the course of EAE. In the early stage of EAE, inflammatory cells first appeared in the subarachnoid space (SAS) and infiltrated the subpial region. The majority of inflammatory cells in SAS expressed TCR alpha beta and either CD4 or CD8 molecules. However, only CD4+ T cells infiltrated the parenchyma while the majority of CD8+ cells remained in SAS. A similar differential localization of T cells was observed with regard to CD45RC molecules. Inflammatory cells in SAS consisted of both CD45RC+ and CD45RC- population, while those in the parenchyma were largely CD45RC-. With regard to adhesion molecules, the leptomeninges constitutively expressed fibronectin (FN) and intercellular adhesion molecule 1 (ICAM-1). Most SAS inflammatory cells expressed very late activation antigen 4 (VLA-4) and, to lesser extent, lymphocyte function-associated antigen 1 (LFA-1) in the early stage of EAE. On the other hand, parenchymal infiltrating cells expressed LFA-1 more strongly in the peak stage. Double staining for V beta 8.2 TCR and microglia demonstrated an increase in the number of microglia together with morphological changes into rod-shape cells in the vicinity of infiltrating T cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7860713 TI - Stress-induced glucocorticoid response modulates mononuclear cell trafficking during an experimental influenza viral infection. AB - The migration, distribution, and localization of lymphoid cells throughout the body is critical to the efficiency and development of the immune response. This study examined the role of endogenous glucocorticoids in mononuclear cell (MNC) trafficking during the development of an immune response to infection by influenza A/PR8 virus. Accumulation of MNC in the draining lymph nodes and at the site of virus replication (lungs) was studied in infected mice, and infected mice subjected to a stressor (physical restraint). The glucocorticoid antagonist, RU486, was used to block the activity of endogenous corticosterone during development of the immune response. PR8-infected mice demonstrated an elevation in circulating corticosterone regardless of whether they were treated with RU486 or a placebo. Thus, some 'afferent' signal associated with the infection, and/or the immune response to infection, activated the hypothalamic-pituitary-adrenal axis (HPA) and was not subject to negative feedback regulation. The initial accumulation of MNC in the draining lymph nodes and lungs during infection, however, was independent of the glucocorticoid response. Our previous studies demonstrated that virally infected animals subjected to physical restraint had highly elevated plasma corticosterone levels, suppressed lymphadenopathy, and reduced accumulation of MNC in the lungs. In the present study, RU486 treatment restored cellularity to the draining lymph nodes and enhanced accumulation of MNC in lungs of stressed, A/PR8 virus-infected mice. PMID- 7860714 TI - A sulfatide-reactive human monoclonal antibody obtained from a multiple sclerosis patient selectively binds to the surface of oligodendrocytes. AB - In a previous paper, we described the production of a sulfatide-reactive IgM antibody-secreting B cell line that was obtained by Epstein-Barr virus transformation of peripheral B cells from a patient with multiple sclerosis (MS) (Uhlig and Dernick, 1989). In the present study, we demonstrate that this human monoclonal antibody (humAb) DS1F8 selectively binds to the surface of living oligodendrocytes in mixed brain cell cultures of newborn rats. Since a mouse mAb reactive with sulfatide was shown to inhibit oligodendrocyte progenitor differentiation, autoantibodies with binding specificities similar to DS1F8 could play a role in the demyelinating process in the CNS. PMID- 7860715 TI - Beta-adrenergic agonists suppress chronic/relapsing experimental allergic encephalomyelitis (CREAE) in Lewis rats. AB - Chronic/relapsing experimental allergic encephalomyelitis (CREAE) serves as an animal model for relapsing/remitting multiple sclerosis. Treatment with the beta adrenergic agonist isoproterenol or the beta 2-adrenergic agonist terbutaline significantly suppressed both the first acute attack and the number of relapses in CREAE Lewis rats. The number of relapses was decreased even when treatment with beta-adrenergic agonist was started after the onset of the first acute attack of CREAE. beta-adrenergic receptor number was increased significantly on splenocytes from CREAE rats as compared to healthy controls or CFA-injected rats. Terbutaline treatment of CREAE rats lowered the splenocyte receptor number to normal values. PMID- 7860716 TI - Reactive oxygen species are involved in the pathogenesis of experimental allergic encephalomyelitis in Lewis rats. AB - During experimental allergic encephalomyelitis (EAE), both blood-borne macrophages as well as activated, resident microglial cells are considered to be involved in inflammatory reactions in the central nervous system (CNS), resulting in the neurological deficits common to EAE. Both cell types can produce multiple mediators of tissue damage, among which are the reactive oxygen species (ROS). In this study we show that macrophages and microglial cells, isolated from the CNS of Lewis rats with clinical signs of EAE, exhibited significantly elevated spontaneous and phorbol myristate acetate (PMA)-inducible levels of ROS compared to similar cells isolated from healthy controls, sham (complete Freund's adjuvant, CFA)-immunized rats as well as rats sacrificed before the manifestation of clinical signs of EAE. However, during clinical EAE, peripheral blood mononuclear cells (PBMC) did not show increased spontaneous nor PMA-inducible ROS production compared to controls. In vivo treatment of EAE with catalase, which scavenges the ROS H2O2, markedly suppressed the severity of the disease as compared to sham (albumin)-treated controls. In contrast, superoxide dismutase had no effect on clinical signs. Our studies point at a putative functional role for ROS, and in particular H2O2, in the pathogenesis of EAE. PMID- 7860717 TI - Vasopressin is located within lymphocytes in the rat spleen. AB - Using dual antigen immunocytochemical staining with a specific antiserum for arginine vasopressin (AVP), we have detected AVP immunoreactivity in clusters of large immunoglobulin (Ig) G-containing cells, probably plasma cells, within the rat spleen, and in smaller cells which are IgG-negative. Vasopressin-positive cells were detected principally throughout the white pulp areas in the subcortical region of the spleen. IgG staining could only be detected within the cells and not on the cell surface, demonstrating that the antiserum is recognising genuine intracellular IgG and not cell surface antigens. Reversed phase HPLC of spleen tissue extract revealed a single peak of AVP immunoreactivity which co-eluted with the standard. This is the first evidence that AVP is found within lymphocytes of the immune system and provides further information about the important interaction between the endocrine and immune systems. PMID- 7860718 TI - Cutaneous sensory receptors. AB - The range of sensations elicitable from the skin is wide. We review the complex and diverse nature of cutaneous sense organs and the way these cutaneous receptors function as transducers of information from the skin. The discussion touches on the afferent properties of various classes of cutaneous receptors, the conduction velocity of their peripheral nerve fibers, the morphology of the receptor terminal, and the mode of sensation evoked. A brief view of associated features of dorsal root ganglion neurons is also provided. PMID- 7860719 TI - Causes and diagnosis of sensory neuropathies: a review. AB - Sensory neuropathies are rare but unique peripheral neuropathies that involve only the peripheral sensory system. The diagnosis is made by both clinical and electrophysiological findings. Sensory neuropathies occur predominantly in women. The symptoms begin in the arms more often than the legs and occur asymmetrically. Pain and severe sensory ataxia in varying degrees are the main presenting symptoms. Definable causes of sensory neuropathies are hereditary, paraneoplastic, immunological, metabolic, infectious, and drug-induced disorders. In our experience, however, nearly half of all sensory neuropathies have been idiopathic. The clinical course of these sensory neuropathies is variable. The symptoms clearly worsened in 25% of our patients, but in the rest remained unchanged for many years, resulting in a poor functional prognosis because of intractable pain and ataxia. Most sensory neuropathies are resistant to any treatment. We review the electrophysiological features, laboratory findings, and nerve biopsy results in our patients and discuss in detail the potential underlying diseases included in the differential diagnosis. PMID- 7860720 TI - Quantitative sensory testing: methodology, applications, and future directions. AB - Quantitative sensory testing (QST) is based on well-developed psychophysical methods that define not only the stimulus (type, characteristics, quantity, presentation, testing format, and environment) but also the response (form and analysis). With the availability of personal computers, transducers, electronic circuitry, and specially written software, it became possible to develop systems that delivered physical stimuli with waveforms that were precisely defined, quantitated, and graded over a broad range of magnitudes, and capable of eliciting unitary sensations. Specific algorithms of testing and finding threshold could now be programmed for exact and sequential error-free testing. Results could also be efficiently and accurately printed out and compared with normal values with consideration of modality, site, gender, height, and weight. QST's main application is in quantifying modality-specific detection thresholds (and some suprathresholds also) in health (by site, side, development, aging, and other) and in disease (involving sensory receptors, nerve fibers, central nervous system tracts, or cerebral association areas), allowing it to play the unique role of standardizing the clinical examination. Used to identify modality specific sensory loss it can, for example, be correlated with the compound action potential of sural nerve in vitro and with the number and sizes of fibers. In detecting patterns of sensory abnormality, it can also suggest the presence of specific diseases and be used to follow the course of sensory loss. Finally, because it is the best approach to detect, characterize, and quantitate sensory abnormality, it is useful both in epidemiologic and controlled clinical trials. Although our review focuses especially on the approaches and system we have developed, other systems using standardized approaches are available allowing the evaluation of vibratory (VDT), cooling (CDT), and warming (WDT) detection thresholds and visual analog scaling of heat pain (HP VAS). PMID- 7860721 TI - Sensory nerve conduction studies. AB - Sensory nerve conduction studies (NCS) are an indispensable component of the electrodiagnostic examination. They evolved from mixed NCS, and were initially described by Dawson in 1950. Gilliatt and Sears first reported their clinical value in 1958. Compared to motor NCS, sensory NCS are much less standardized. Variables regarding them include: (a) bipolar vs. monopolar recording; (b) antidromic vs. orthodromic technique; (c) needle vs. surface stimulating electrode(s); (d) needle vs. surface recording electrodes; (e) fixed vs. variable distances between cathode and active recording electrode; (f) measuring latencies to onset vs. to peak; and (g) measuring amplitudes baseline to peak vs. peak to peak. The value of sensory NCS with various peripheral nerve fiber lesions, including plexopathies, mononeuropathies, and polyneuropathies, is discussed. PMID- 7860722 TI - Visual, auditory, and somatosensorial evoked potentials in early and late treated adolescents with phenylketonuria. AB - Pattern reversal visual, auditory, and somatosensorial evoked potentials were recorded in two groups of phenylketonuric (PKU) adolescents after protracted exposition to high concentrations of phenylalanine following diet discontinuation. The first group consisted of 11 early treated (before age 3 months) PKU patients (ET-PKU); the second group consisted of 11 late detected (after age 8 months), symptomatic, PKU subjects (LT-PKU). Despite the relevant lag between the two groups in mental development and neurological status, no clear-cut difference in evoked potentials could be detected. Only the wave I latency of the brainstem auditory evoked potentials (BAEPs) was significantly shorter in ET- versus LT-PKU children. The P100 latency, I-V interpeak latency (IPL), and I-III IPL seem to discriminate the less severe form of PKU (ET-PKU type 3) from the most severe forms, ET-PKU type 1 plus 2 and LT-PKU. No correlations were found between clinical, biochemical, and neurophysiological parameters. The present data suggest that evoked potentials technique is of limited sensitivity in detecting central nervous system (CNS) alterations in PKU adolescents after diet discontinuation. PMID- 7860724 TI - Genetic mosaicism: what Gregor Mendel didn't know. PMID- 7860723 TI - Measuring intracerebral osmolytes in hyponatremic disorders. PMID- 7860725 TI - cGMP inhibition of heart phosphodiesterase: is it clinically relevant? PMID- 7860726 TI - Specific inhibition of eIF-5A and collagen hydroxylation by a single agent. Antiproliferative and fibrosuppressive effects on smooth muscle cells from human coronary arteries. AB - Restenosis occurs in 35% of patients within months after balloon angioplasty, due to a fibroproliferative response to vascular injury. These studies describe a combined fibrosuppressive/antiproliferative strategy on smooth muscle cells cultured from human primary atherosclerotic and restenotic coronary arteries and from normal rat aortas. L-Mimosine suppressed the posttranslational hydroxylation of the precursors for collagen and for eukaryotic initiation factor-5A (eIF-5A) by directly inhibiting the specific protein hydroxylases involved, prolyl 4 hydroxylase (E.C. 1.14.11.2) and deoxyhypusyl hydroxylase (E.C. 1.14.99.29), respectively. Inhibition of deoxyhypusyl hydroxylation correlated with a dose dependent inhibition of DNA synthesis. Inhibition of prolyl hydroxylation caused a dose-dependent reduction in the secretion of hydroxyproline-containing protein and decreased the formation of procollagen types I and III. The antifibroproliferative action could not be attributed to nonspecific or toxic effects of mimosine, appeared to be selective for the hydroxylation step in the biosynthesis of the procollagens and of eIF-5A, and was reversible upon removal of the compound. The strategy of targeting these two protein hydroxylases has important implications for the pathophysiology of restenosis and for the development of agents to control fibroproliferative diseases. PMID- 7860727 TI - Extinction of autonomous growth potential in embryonic: adult vascular smooth muscle cell heterokaryons. AB - Vascular smooth muscle cells (SMC) isolated from embyronic and early fetal (e13 e18) rat aortas exhibit an "embryonic growth phenotype" in culture (Cook, C. L., M. C. M. Weiser, P. E. Schwartz, C. L. Jones, and R. A. Majack. 1994. Circ. Res. 74:189-196). Cells in this growth phenotype exhibit autonomous, serum-independent replication, in contrast to SMC in the "adult" growth phenotype, whose proliferation in culture is dependent on exogenous mitogens. To determine which of these two phenotypes is genetically dominant, heterokaryons were constructed between adult and embryonic (day e17) rat aortic SMC. The fused cells were maintained in serum-free medium for 3 d, then were labeled with bromodeoxyuridine (BrdU) for an additional 24 h. Under these conditions, parental e17 SMC exhibited a high rate of self-driven DNA synthesis (73-85% BrdU-positive cells), while parental adult SMC showed minimal replication (13-21% BrdU-positive cells). Homokaryons of parental cells exhibited parental growth phenotypes and showed the expected mitogenic response when stimulated with serum. Heterokaryons between e17 and adult SMC exhibited a nonautonomous growth phenotype; the "adult" growth phenotype was calculated to be dominant in > 89% of all true heterokaryons. The data suggest that adult SMC express molecules capable of genetically extinguishing or otherwise inhibiting the autonomous replication of embryonic SMC. PMID- 7860728 TI - Inhibition of diet-induced atheroma formation in transgenic mice expressing apolipoprotein E in the arterial wall. AB - Apolipoprotein E (apoE) plays a crucial role in lipoprotein metabolism both in plasma and in peripheral tissues. To test whether apoE in the vascular wall has a direct and local effect on atherogenesis, we established transgenic mice expressing human apoE under control of H2 Ld promoter. Studies on mRNA levels and immunohistochemistry demonstrated that this line was characterized by high expression of human apoE in the arterial wall while its expression was relatively low in other tissues as compared with the respective endogenous expression of mouse apoE. They showed no difference in plasma cholesterol levels and lipoprotein profile from controls when fed both normal and atherogenic diets. However, after 24 wk of an atherogenic diet, the formation of fatty streak lesions in proximal aorta was markedly inhibited in transgenic mice as compared with controls. Both lesion area and esterified cholesterol content were < 30% of those in controls. In a tissue cholesterol labeling study with 3H-cholesterol, the specific activity of aorta cholesterol was much less in transgenic mice, suggesting that apoE enhances cholesterol efflux from the aortic wall into plasma. Thus, apoE has anti-atherogenic action which is mediated via enhancing reverse cholesterol transport from arterial wall. PMID- 7860730 TI - Sensitization to self (virus) antigen by in situ expression of murine interferon gamma. AB - Autoimmune disease results from inflammatory destruction of tissues by aberrant self-reactive lymphocytes. We studied the autoimmune potential of T lymphocytes immunologically ignorant of viral antigens acting as self antigens and whether the host defense molecule IFN-gamma could stimulate these cells to cytotoxic competency. For this purpose, we produced double transgenic mice expressing pancreatic IFN-gamma as well as lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP) or glycoprotein (GP) antigen. 100% of the NP+/IFN-gamma+ mice became diabetic before 2 mo of age, while none of the NP single transgenic littermates and only 10% of IFN-gamma single transgenic littermates did. Strikingly, NP+/IFN-gamma+ mice spontaneously developed cytotoxic T lymphocyte activity on LCMV-infected targets and vaccinia virus-NP-infected ones without prior LCMV infection but NP+/IFN-gamma- mice did not, which indicates specific sensitization to the viral antigen by IFN-gamma. These results suggest that lymphocytes ignorant of self antigens can be activated by IFN-gamma released after immunologic stimulation such as viral infection. This mechanism may account for the loss of apparent tolerance to self antigens in autoimmune diseases such as insulin-dependent diabetes mellitus. PMID- 7860729 TI - Focal expression of interleukin-2 does not break unresponsiveness to "self" (viral) antigen expressed in beta cells but enhances development of autoimmune disease (diabetes) after initiation of an anti-self immune response. AB - The participation of IL-2 in insulin-dependent (type 1) diabetes (IDDM) was analyzed in transgenic (tg) mice expressing the nucleoprotein (NP) of lymphocytic choriomeningitis virus and IL-2 under control of the rat insulin promoter focally in beta cells of the islets of Langerhans. Insertion and expression of the viral (self) gene or of the IL-2 gene alone did not lead to IDDM. Infiltration primarily of CD4 and B lymphocytes and increased expression of MHC class I and II molecules occurred in islets where IL-2 was expressed. By contrast, neither cellular infiltrates nor expression of MHC class I or II glycoproteins above base levels was noted in tgs expressing the viral protein alone. Double tg mice expressing both the viral protein and IL-2 in their islets displayed a modest increase in incidence of spontaneous diabetes compared with that of single transgenic mice expressing IL-2 alone. Breaking of immunological unresponsiveness or sensitization to self antigens did not occur. Neither cytotoxic T lymphocytes (CTL) nor antibodies directed against the viral tg (NP) were generated. However, after challenge with lymphocytic choriomeningitis virus, double tg mice developed anti-self (viral) CTL and IDDM (incidence > 95%) within 2 mo. The generation of virus ("self")-specific MHC-restricted CTL was dependent on CD4+ help. In contrast, viral inoculum to single tg mice expressing either the viral protein or IL-2 failed to enhance the incidence of IDDM over 30% for viral protein or 10% for IL-2 after an 8-mo observation period. Hence, in this autoimmune model in situ expression of IL-2 did not break unresponsiveness but markedly enhanced ongoing disease. PMID- 7860732 TI - Two missense mutations in the beta-globin gene can cause severe beta thalassemia. Hemoglobin Medicine Lake (beta 32[B14]leucine-->glutamine; 98 [FG5] valine- >methionine). AB - We studied the molecular basis of transfusion-dependent hemolytic anemia in an infant who rapidly developed the phenotype of beta thalassemia major. DNA sequence of one beta-globin gene of the proband revealed two mutations, one for the moderately unstable hemoglobin (Hb) Koln and another for a novel codon 32 cytosine-thymidine-guanine-->cytosine-adenine-guanine transversion encoding a leucine-->glutamine mutation. A hydrophilic glutamine residue at beta 32 has an uncharged polar side chain that could potentially distort the B helix and provoke further molecular instability. This new hemoglobin was called Hb Medicine Lake. Biosynthesis studies showed a deficit of beta-globin synthesis with early loss of beta-globin chains. An abnormal unstable hemoglobin, globin chain, or tryptic globin peptide was not present, demonstrating the extreme lability of this novel globin. Hb Medicine Lake mRNA was present, but an aberrantly spliced message was not. Absence of an abnormal beta-globin gene in the mother makes it likely that a de novo mutation occurred in the proband. The molecular pathogenesis of Hb Medicine Lake illustrates a mechanism whereby the phenotype of a genetic disorder, like the mild hemolytic anemia associated with a hemoglobinopathy, can be modulated by a coincident mutation in the same gene. PMID- 7860731 TI - Gene transfer into the airway epithelium of animals by targeting the polymeric immunoglobulin receptor. AB - Genes of interest can be targeted specifically to respiratory epithelial cells in intact animals with high efficiency by exploiting the receptor-mediated endocytosis of the polymeric immunoglobulin receptor. A DNA carrier, consisting of the Fab portion of polyclonal antibodies raised against rat secretory component covalently linked to poly-L-lysine, was used to introduce plasmids containing different reporter genes into airway epithelial cells in vivo. We observed significant levels of luciferase enzyme activity in protein extracts from the liver and lung, achieving maximum values of 13,795 +/- 4,431 and 346,954 +/- 199,120 integrated light units (ILU) per milligram of protein extract, respectively. No luciferase activity was detected in spleen or heart, which do not express the receptor. Transfections using complexes consisting of an irrelevant plasmid (pCMV lacZ) bound to the bona fide carrier or the expression plasmid (pGEMluc) bound to a carrier based on an irrelevant Fab fragment resulted in background levels of luciferase activity in all tissues examined. Thus, only tissues that contain cells bearing the polymeric immunoglobulin receptor are transfected, and transfection cannot be attributed to the nonspecific uptake of an irrelevant carrier-DNA complex. Specific mRNA from the luciferase gene was also detected in the lungs of transfected animals. To determine which cells in the lungs are transfected by this method, DNA complexes were prepared containing expression plasmids with genes encoding the bacterial beta-galactosidase or the human interleukin 2 receptor. Expression of these genes was localized to the surface epithelium of the airways and the submucosal glands, and not the bronchioles and alveoli. Receptor-mediated endocytosis can be used to introduce functional genes into the respiratory epithelium of rats, and may be a useful technique for gene therapy targeting the lung. PMID- 7860733 TI - Modulation of in vitro splicing of the upstream intron by modifying an intra-exon sequence which is deleted from the dystrophin gene in dystrophin Kobe. AB - Molecular analysis of dystrophin Kobe showed that exon 19 of the dystrophin gene bearing 52-bp deletion was skipped during splicing, although the known consensus sequences at the 5' and 3' splice sites of exon 19 were maintained (Matsuo, M., T. Masumura, H. Nishio, T. Nakajima, Y. Kitoh, T. Takumi, J. Koga, and H. Nakamura. 1991. J. Clin. Invest. 87:2127-2131). These data suggest that the deleted sequence of exon 19 may function as a cis-acting element for exact splicing for the upstream and downstream introns. To investigate this potential role of exon 19, an in vitro splicing system using artificial dystrophin mRNA precursors (pre-mRNAs) was established. Pre-mRNA containing exon 18, truncated intron 18, and exon 19 was spliced precisely in vitro, whereas splicing of intron 18 was almost completely abolished when the wild-type exon 19 was replaced by the dystrophin Kobe exon 19. Splicing of intron 18 was not fully reactivated when dystrophin Kobe exon 19 was restored to nearly normal length by inserting other sequences into the deleted site. These results suggest that the presence of the exon 19 sequence which is lost in dystrophin Kobe is more critical for splicing of intron 18 than the length of the exon 19 sequence. Characteristically, the efficiency of splicing of this intron seemed to correlate with the presence of polypurine tracks within the downstream exon 19. Moreover, an antisense 31-mer 2' O-methyl ribonucleotide complementary to the 5' half of the deleted sequence in dystrophin Kobe exon 19 inhibited splicing of wild-type pre-mRNA in a dose- and time-dependent manner. This first in vitro evidence that dystrophin pre-mRNA splicing can be modulated by an antisense oligonucleotide raises the possibility of a new therapeutic approach for Duchenne muscular dystrophy. PMID- 7860734 TI - Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif. AB - The HLA class I-restricted cytotoxic T lymphocyte (CTL) response is a major defense mechanism in viral infections. It has been suggested that the CTL response may contribute to viral clearance and liver cell injury during hepatitis C virus (HCV) infection. To test this hypothesis requires an understanding of the characteristics of HCV-specific cytotoxic effector cells and identification of the target antigens to which they respond. To begin this process we stimulated peripheral blood mononuclear cells (PBMC) from a group of HLA-A2 positive patients with chronic hepatitis C with a panel of 130 HCV-derived peptides containing the HLA-A2 binding motif. Effector cells were tested for their capacity to lyse HLA-A2-matched target cells that were either sensitized with peptide or infected with a vaccinia virus construct containing HCV sequences. Using this approach we have identified nine immunogenic peptides in HCV, three of which are derived from the putative core protein, three from the nonstructural (NS) 3 domain, two from NS4 and one from NS5. Selected responses were shown to be HLA-A2 restricted, mediated by CD8+ T cells and to recognize endogenously synthesized viral antigen. Unexpectedly, peptide-specific CTL responses could also be induced in sero-negative individuals, suggesting in vitro activation of naive CTL precursors. The precursor frequency of peptide-specific CTL was 10 to 100-fold higher in infected patients compared to uninfected controls, and the responses were greatly diminished by removal of CD45 RO+ (memory) T cells. Further quantitative studies are clearly required to establish whether a correlation exists between the HCV-specific CTL response and the clinical course of this disease. Definition of the molecular targets of the human CTL response to HCV creates this opportunity, and may also contribute to the development of a T cell-based HCV vaccine. PMID- 7860735 TI - Structure and specificity of T cell receptors expressed by potentially pathogenic anti-DNA autoantibody-inducing T cells in human lupus. AB - The production of potentially pathogenic anti-DNA autoantibodies in SLE is driven by special, autoimmune T helper (Th) cells. Herein, we sequenced the T cell receptor (TCR) alpha and beta chain genes expressed by 42 autoimmune Th lines from lupus patients that were mostly CD4+ and represented the strongest inducers of such autoantibodies. These autoimmune TCRs displayed a recurrent motif of highly charged residues in their CDR3 loops that were contributed by N-nucleotide additions and also positioned there by the recombination process. Furthermore, Th lines from four of the five patients showed a marked increase in the usage of the V alpha 8 gene family. Several independent Th lines expressed identical TCR alpha and/or beta chain sequences indicating again antigenic selection. 10 of these Th lines could be tested further for antigenic specificity. 4 of the 10 pathogenic anti-DNA autoantibody-inducing Th lines responded to the non-histone chromosomal protein HMG and two responded to nucleosomal histone proteins; all presented by HLA-DR molecules. Another Th line responded to purified DNA more than nucleosomes. Thus, these autoimmune Th cells of lupus patients respond to charged epitopes in various DNA-binding nucleoproteins that are probably processed and presented by the anti-DNA B cells they selectively help. PMID- 7860736 TI - Polyol profiles in Down syndrome. myo-Inositol, specifically, is elevated in the cerebrospinal fluid. AB - Polyols are reduction products of aldoses and ketoses; their concentrations in tissues can reflect carbohydrate metabolism. Several polyol species were quantitated in cerebrospinal fluid (CSF) and plasma from 10 Down Syndrome (trisomy 21) subjects between the ages of 22 and 63 years (3 of whom were demented) and from 10 healthy age-matched controls, using a gas chromatographic/mass spectrometric technique. The mean CSF concentration and the mean CSF/plasma concentration ratio of myo-inositol were significantly elevated in Down syndrome compared with controls, but were not correlated with the presence of dementia in the Down subjects. Plasma myo-inositol was not significantly altered in these subjects. No significant difference between Down syndrome and controls was found for CSF concentrations of mannitol, sorbitol, galactitol, ribitol, arabitol, or 1,5-anhydrosorbitol, but plasma mannitol, ribitol and arabitol were elevated in Down syndrome. The present observation provides new impetus for studying synthesis and transport of myo-inositol as well as phosphatidylinositol cycle in trisomy 21 disorder. PMID- 7860737 TI - The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell lymphotropic virus-associated disease. A study of 50 patients. AB - For nearly two decades it has been suspected that the cutaneous T cell lymphoma, mycosis fungoides (MF), and its leukemic variant, the Sezary syndrome, are caused by the human T lymphotropic virus (HTLV-I/II). Arguments against this concept included the finding that only a small number of MF patients have antibodies to HTLV-I/II and that attempts to detect proviral sequences by mere Southern hybridization of extracted DNA usually met with failure. However, we have reported repeatedly that HTLV-like particles emerge in blood mononuclear cell (PBMC) cultures of practically all patients with this disease. In several instances, the particles were identified as HTLV by immunoelectron microscopy as well as biomolecular analysis. With the assumptions that the virus in MF patients may have become detection by Southern hybridization alone, the extracts of freshly isolated PBMC of 50 consecutive patients were subjected to combined PCR/Southern analysis. Here we report the presence of HTLV pol and/or tax proviral sequences in 46 out of 50 (92%) of the patients tested. In addition, five of the patients, who lacked antibodies to HTLV-I/II structural proteins, were found to be seropositive for tax. It thus seems reasonable to conclude that MF/Sezary syndrome is an HTLV-associated disease and that lack of an immune response does not preclude infection with this type of virus. PMID- 7860738 TI - Cellular and molecular events leading to mitochondrial toxicity of 1-(2-deoxy-2 fluoro-1-beta-D-arabinofuranosyl)-5-iodouracil in human liver cells. AB - We have explored the mechanism(s) related to FIAU-induced liver toxicity, particularly focusing on its effect on mitochondrial function in a human hepatoma cell line-HepG2. The potential role of FMAU and FAU, metabolites detected in FIAU treated patients were also ascertained. FIAU and FMAU inhibited cell growth and were effectively phosphorylated. A substantial increase in lactic acid production in medium of cells incubated with 1-10 microM FIAU or FMAU was consistent with mitochondrial dysfunction. Slot blot analysis demonstrated that a two week exposure to 10 microM FIAU or FMAU was not associated with a decrease in total mitochondrial (mt) DNA content. However, FIAU and FMAU were incorporated into nuclear and mtDNA and relative values suggest that both compounds incorporate at a much higher rate into mtDNA. Electron micrographs of cells incubated with 10 microM FIAU or FMAU revealed the presence of enlarged mitochondria with higher cristae density and lipid vesicles. In conclusion, these data suggest that despite the lack of inhibition of mtDNA content, incorporation of FIAU and FMAU into mtDNA of HepG2 cells leads to marked mitochondrial dysfunction as evidenced by disturbance in cellular energy metabolism and detection of micro- and macrovesicular steatosis. PMID- 7860739 TI - Induction of B cell apoptosis by TH0, but not TH2, CD4+ T cells. AB - Engagement of the T cell receptor molecules with MHC-antigen complexes presented by B cells ascertains antigen specificity in T cell-dependent help. Ligation of MHC molecules on the surface of B cells, however, has not only been implicated in antigen-specific T-B cell interaction, but has also been linked to the induction of B cell apoptosis. To examine the role of T helper cells in either induction of immunoglobulin synthesis or B cell apoptotic death, we have facilitated T cell receptor-MHC interaction through a bacterial superantigen. CD4+ T cell clones could be categorized into two clearly distinct subsets based upon their ability to promote B cell help in the presence of superantigen. One subset of T cell clones supported immunoglobulin synthesis, and thus functioned as effective helper cells. B cells interacting with the second subset of T cells did not differentiate into antibody-secreting cells, but underwent apoptosis. Both types of helper cells were able to provide contact help after anti-CD3 stimulation. Induction of apoptosis was a dominant phenomenon; the addition of the superantigen suppressed immunoglobulin production in B cells activated by anti CD3-stimulated helper T cells, indicating that the T cells delivered an apoptotic signal to the B cell. T cell clones providing effective MHC restrictive B cell help could be distinguished from T cells facilitating B cell apoptosis based on their lymphokine secretion profile. Induction of B cell apoptosis was a feature of T cells with a TH0 lymphokine pattern. Promotion of MHC-restricted B cell help was associated with a TH2 lymphokine profile. TH1-derived cytokines alone could not substitute for apoptosis-inducing T cells. PMID- 7860740 TI - Direct demonstration of increased expression of Thomsen-Friedenreich (TF) antigen in colonic adenocarcinoma and ulcerative colitis mucin and its concealment in normal mucin. AB - Increased binding of the lectin peanut agglutinin is a common feature in epithelial malignancy and hyperplasia. This may have considerable functional importance in the intestine by allowing interaction between the epithelium and mitogenic lectins of dietary or microbial origin. Peanut agglutinin binds the disaccharide Thomsen-Friedenreich (TF, T or core 1) blood group antigen, Gal beta (1-3) GalNAc alpha-, but is not totally specific for this site. Consequently, there has been controversy about the presence of this structure in colon cancer; studies with anti-TF monoclonal antibodies have failed to detect it. We have examined the presence of TF antigen in colonic mucus glycoprotein (mucin) using endo-alpha-N-acetylgalactosaminidase (O-Glycanase), which specifically catalyzes the hydrolysis of TF antigen from glycoconjugates. Samples of adenocarcinoma, inflammatory bowel disease (ulcerative colitis), and normal mucin were treated with O-glycanase, the liberated disaccharide was separated from the glycoprotein and analyzed using dual CarboPac PA-100 column high performance anion-exchange chromatography coupled with pulsed amperometric detection. O-Glycanase treatment released increased amounts of TF antigen from both colonic adenocarcinoma (8.0 +/ 3.9 ng/micrograms protein, n = 11; P < 0.0001 ANOVA) and ulcerative colitis mucin (3.3 +/- 0.3 ng/micrograms protein, n = 5; P = 0.04) compared with mucin samples from histologically normal mucosa distant from carcinoma (1.5 +/- 1.1 ng/micrograms protein, n = 9). However, after mild acid treatment to remove sialic acids and fucose, releasable TF antigen was increased in all nine of these histologically normal mucin samples (5.5 +/- 2.6 ng/micrograms protein, P < 0.0002). We conclude that TF antigen is an oncofetal antigen which is expressed in colon cancer, but is concealed by further glycosylation (sialylation and/or fucosylation) in the normal colonic mucosa. PMID- 7860741 TI - Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors. AB - Allergic symptoms result from the release of granular and lipidic mediators and of cytokines by inflammatory cells. The whole process is initiated by the aggregation of mast cell and basophil high-affinity IgE receptors (Fc epsilon RI) by IgE and antigen. We report here that IgE-induced release of mediator and cytokine can be inhibited by cross-linking Fc epsilon RI to low-affinity IgG receptors (Fc gamma RII) which are constitutively expressed on mast cells and basophils. Using a model of stable transfectants in RBL-2H3 cells expressing endogeneous rat Fc epsilon RI and recombinant murine Fc gamma RII, we showed that inhibition requires that Fc epsilon RI be crosslinked to Fc gamma RII by the same multivalent ligand. Inhibition of cross-linked receptors left non-cross-linked Fc epsilon RI capable of triggering mediator release and was reversible upon disengagement. Both isoforms of wild-type Fc gamma RII were equally capable of inhibiting Fc epsilon RI-mediated mast cell activation provided they had an intact intracytoplasmic domain. Our results demonstrate that mast cell secretory responses triggered by high-affinity receptors for IgE may be controlled by low affinity receptors for IgG. This regulation of Fc epsilon RI-mediated mast cell activation is of potential interest in mast cell physiology and in allergic pathology. PMID- 7860742 TI - Enhanced interleukin-8 release and gene expression in macrophages after exposure to Mycobacterium tuberculosis and its components. AB - Mycobacterium tuberculosis infection is accompanied by acute and chronic inflammatory infiltrates associated with necrotizing granulomas in lung tissue. The cellular infiltrate is characterized by inflammatory cells which include neutrophils, lymphocytes, and macrophages. In animal and in vitro models of mycobacterial infection, cytokines including tumor necrosis factor-alpha (TNF alpha), interferon gamma (IFN-gamma), and interleukin-1 beta (IL-1 beta) participate in granulomatous inflammation. We hypothesized that interleukin-3, a potent chemoattractant for neutrophils and lymphocytes, could be released by activated alveolar macrophages after exposure to M. tuberculosis or its components and contribute to granulomatous lung inflammation. A quantitative immunoassay revealed that IL-8 protein release was significantly elevated in supernatants of macrophages and in lavage fluid obtained from patients with pulmonary tuberculosis compared to normal controls. In addition, Northern blots demonstrated striking up-regulation of IL-8 mRNA in macrophages from these patients. M. tuberculosis and its cell wall components lipoarabinomannan (LAM), lipomannan (LM), and phosphoinositolmannoside (PIM) stimulated IL-8 protein release and mRNA expression in vitro from alveolar macrophages, but deacylated LAM did not. Neutralizing antibodies to TNF-alpha and/or IL-1-alpha and beta blocked 83% of the stimulation. IL-8 synthesis and release is an early response of macrophages after phagocytosis of M. tuberculosis. Its production serves to attract both acute and chronic inflammatory cells of active infection and thus participates in the process of containment of the pathogen. PMID- 7860743 TI - Evidence that the brain of the conscious dog is insulin sensitive. AB - The aim of this study was to determine whether a selective increase in the level of insulin in the blood perfusing the brain is a determinant of the counterregulatory response to hypoglycemia. Experiments were carried out on 15 conscious 18-h-fasted dogs. Insulin was infused (2 mU/kg per min) in separate, randomized studies into a peripheral vein (n = 7) or both carotid and vertebral arteries (n = 8). This resulted in equivalent systemic insulinemia (84 +/- 6 vs. 86 +/- 6 microU/ml) but differing insulin levels in the head (84 +/- 6 vs. 195 +/ 5 microU/ml, respectively). Glucose was infused during peripheral insulin infusion to maintain the glucose level (56 +/- 2 mg/dl) at a value similar to that seen during head insulin infusion (58 +/- 2 mg/dl). Despite equivalent peripheral insulin levels and similar hypoglycemia; steady state plasma epinephrine (792 +/- 198 vs. 2394 +/- 312 pg/ml), norepinephrine (404 +/- 33 vs. 778 +/- 93 pg/ml), cortisol (6.8 +/- 1.8 vs. 9.8 +/- 1.6 micrograms/dl) and pancreatic polypeptide (722 +/- 273 vs. 1061 +/- 255 pg/ml) levels were all increased to a greater extent during head insulin infusion (P < 0.05). Hepatic glucose production, measured with [3-3H]glucose, rose from 2.6 +/- 0.2 to 4.3 +/- 0.4 mg/kg per min (P < 0.01) in response to head insulin infusion but remained unchanged (2.6 +/- 0.5 mg/kg per min) during peripheral insulin infusion. Similarly, gluconeogenesis, lipolysis, and ketogenesis were increased twofold (P < 0.001) during head compared with peripheral insulin infusion. Cardiovascular parameters were also significantly higher (P < 0.05) during head compared with peripheral insulin infusion. We conclude that during hypoglycemia in the conscious dog (a) the brain is directly responsive to physiologic elevations of insulin and (b) the response includes a profound stimulation of the autonomic nervous system with accompanying metabolic and cardiovascular changes. PMID- 7860744 TI - Bactericidal properties of murine intestinal phospholipase A2. AB - We purified a molecule from the murine small intestine that killed both Escherichia coli and Listeria monocytogenes, and identified it as intestinal phospholipase A2 (iPLA2) by NH2-terminal sequencing and enzymatic measurements. The ability of iPLA2 to kill. L. monocytogenes was greatly enhanced by 5 mM calcium, inhibited by EGTA and abolished after reduction and alkylation, suggesting that enzymatic activity was required for iPLA2-mediated bactericidal activity. A mouse-avirulent phoP mutant, S. typhimurium 7953S, was 3.5-fold more susceptible to iPLA2 than its isogenic virulent parent, S. typhimurium 14028S (estimated minimal bactericidal concentrations 12.7 +/- 0.5 micrograms/ml vs. 43.9 +/- 4.5 micrograms/ml P < 0.001). Overall, these findings identify iPLA2 as part of the antimicrobial arsenal that equips Paneth cells to protect the small intestinal crypts from microbial invasion. Because iPLA2 is identical to Type 2 phospholipase A2 molecules found in other sites, including spleen, platelets and inflammatory exudate cells, this enzyme may also contribute to antibacterial defenses elsewhere in the body. PMID- 7860745 TI - Effects of dietary cholesterol and fat saturation on plasma lipoproteins in an ethnically diverse population of healthy young men. AB - The individual effects of dietary cholesterol and fat saturation on plasma lipoprotein concentrations were determined in an ethnically diverse population of normolipidemic young men (52 Caucasian, 32 non-Caucasian). The experimental diets contained approximately 200 or 600 mg/d of cholesterol, 36-38% of calories as fat, and high or low proportions of saturated and polyunsaturated fat (polyunsaturated/saturated fat ratio approximately 0.8 vs 0.3). At the lower cholesterol intake, the high saturated fat diet had only a modest effect on LDL cholesterol in Caucasians (+ 6 mg/dl-1) and none in non-Caucasians. 600 mg cholesterol with high saturated fat led to a substantial mean increase in LDL cholesterol, which was significantly greater in Caucasian than in non-Caucasian subjects (+ 31 mg/dl vs 16 mg/dl, P < 0.005). 600 mg cholesterol with increased polyunsaturated fat gave a mean LDL increase of 16 mg/dl, lower than found when the same high cholesterol intake was coupled with increased saturated fat. Variation in cholesterol rather than the proportions of saturated and polyunsaturated fat had the most influence on LDL-cholesterol levels. Among non Caucasians it was the only significant factor. PMID- 7860746 TI - Insulin-like growth factor-1 enhances ventricular hypertrophy and function during the onset of experimental cardiac failure. AB - To determine whether additional hypertrophy would be beneficial or maladaptive in cardiac failure, the effects of insulin-like growth factor (IGF-1) were investigated in rats with left ventricular (LV) dysfunction. In normal rats, 3 mg/kg per d of recombinant human IGF-1 for 14 d augmented LV wt (32%) and increased LV/body wt ratio (P < 0.01). 2 d after coronary occlusion, rats were randomized to IGF-1 (3 mg/kg per d) or placebo. After 2 wk, IGF-1-treated rats showed significant increases in LV wt (13%) and LV wt/tibial length ratio, but LV/body wt ratio was unchanged. By microangiography, compared with controls (n = 12) IGF-1-treated rats (n = 16) showed increased LV end-diastolic volume (19%) and stroke volume (31%) (both significant normalized to tibial length, but not to body wt). Average infarct size did not differ between groups. The LV ejection fraction (EF) was not significantly different between groups, but estimated cardiac output was higher in treated rats; there was a significant interaction for the EF between infarct size and treatment (P = 0.029) and a trend for EF to be higher in treated rats with large infarctions (EF 33.4 vs 25.1% in controls). Myocyte cross-sectional areas in noninfarcted LV zones tended to be larger in treated rats (232.1 vs 205.4 microns 2; P = 0.10), but there was no difference in capillary density and collagen content did not differ between groups. In conclusion, IGF-1 administration caused hypertrophy of the normal heart in vivo. When stimulated by IGF-1, the severely dysfunctional heart in evolving myocardial infarction is capable of undergoing additional hypertrophy with evidence of improved function, suggesting a beneficial effect. Further investigation of the potential role of growth factor therapy in heart failure appears warranted. PMID- 7860747 TI - Insulin immunization of nonobese diabetic mice induces a protective insulitis characterized by diminished intraislet interferon-gamma transcription. AB - We reported previously that daily injections of isophane insulin prevented both hyperglycemia and insulitis in nonobese diabetic (NOD) mice (Atkinson, M., N. Maclaren; and R. Luchetta. 1990. Diabetes. 39:933-937). The possible mechanisms responsible include reduced immunogenicity of pancreatic beta-cells from "beta cell rest" and induced active immunoregulation to insulin (Aaen, IK., J. Rygaard, K. Josefsen, H. Petersen, C. H. Brogren, T. Horn, and K. Buschard. 1990. Diabetes. 39:697-701). We report here that intermittent immunizations with insulin or its metabolically inactive B-chain in incomplete Freund's adjuvant also prevent diabetes in NOD mice, whereas immunizations with A-chain insulin or with BSA do not. Adoptive transfer of splenocytes from B-chain insulin-immunized mice prevented diabetes in recipients co-infused with diabetogenic spleen cells, an effect that was abolished by prior in vivo elimination of either CD4+ or CD8+ cells. Insulin immunization did not reduce the extent of intraislet inflammation (insulitis); however, it did abolish expression of IFN-gamma mRNA within the insulitis lesions. Immunizations with insulin thus induce an active suppressive response to determinants on the B-chain that converts the insulitis lesion from one that is destructive to one that is protective. PMID- 7860748 TI - The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. AB - Angiotensin II (ANG II) is known to be a potent growth promoting factor for vascular smooth muscle cells and fibroblasts but little is known about its influence on growth in endothelial cells. We studied the effects of ANG II on endothelial growth and the role of the angiotensin receptor subtypes involved. Proliferation of rat coronary endothelial cells (CEC) and rat vascular smooth muscle cells (VSMC) was determined by [3H]thymidine incorporation, the MTT-test and by directly counting cells in a coulter counter. Angiotensin AT1- and AT2 receptors were demonstrated by binding studies and by the presence of their respective mRNA through reverse transcription polymerase chain reaction (RT-PCR). In contrast to VSMC, which in culture only express the AT1-receptor, CEC express both, AT1- and AT2-receptors simultaneously up to the third passage. Whereas ANG II stimulated growth of quiescent VSMC, an effect abolished by pretreatment with the AT1-receptor antagonist, losartan, ANG II did not induce proliferation in quiescent CEC. However, after pretreatment of quiescent endothelial cells (< passage 4) with the AT2-receptor antagonist, PD 123177, ANG II induced proliferation. This effect was reversed by additional pretreatment with losartan. ANG II significantly inhibited the proliferation of bFGF-stimulated CEC in a dose dependent manner by maximally 50%. This effect was prevented by PD 123177 while losartan was ineffective. The AT2-receptor agonist, CGP 42112, mimicked the antiproliferative actions of ANG II, confirming the specificity of the effect. Our results show that the growth modulating actions of ANG II depend on the type of angiotensin receptor present on a given cell. In coronary endothelial cells, the antiproliferative actions of the AT2-receptor offset the growth promoting effects mediated by the AT1-receptor. PMID- 7860749 TI - Hemodynamic and neurohumoral effects of various grades of selective adenosine transport inhibition in humans. Implications for its future role in cardioprotection. AB - In 12 healthy male volunteers (27-53 yr), a placebo-controlled randomized double blind cross-over trial was performed to study the effect of the intravenous injection of 0.25, 0.5, 1, 2, 4, and 6 mg draflazine (a selective nucleoside transport inhibitor) on hemodynamic and neurohumoral parameters and ex vivo nucleoside transport inhibition. We hypothesized that an intravenous draflazine dosage without effect on hemodynamic and neurohumoral parameters would still be able to augment the forearm vasodilator response to intraarterially infused adenosine. Heart rate (electrocardiography), systolic blood pressure (Dinamap 1846 SX; Critikon, Portanje Electronica BV, Utrecht, The Netherlands) plasma norepinephrine and epinephrine increased dose-dependently and could almost totally be abolished by caffeine pretreatment indicating the involvement of adenosine receptors. Draflazine did not affect forearm blood flow (venous occlusion plethysmography). Intravenous injection of 0.5 mg draflazine did not affect any of the measured hemodynamic parameters but still induced a significant ex vivo nucleoside-transport inhibition of 31.5 +/- 4.1% (P < 0.05 vs placebo). In a subgroup of 10 subjects the brachial artery was cannulated to infuse adenosine (0.15, 0.5, 1.5, 5, 15, and 50 micrograms/100 ml forearm per min) before and after intravenous injection of 0.5 mg draflazine. Forearm blood flow amounted 1.9 +/- 0.3 ml/100 ml forearm per min for placebo and 1.8 +/- 0.2, 2.0 +/- 0.3, 3.8 +/- 0.9, 6.3 +/- 1.2, 11.3 +/- 2.2, and 19.3 +/- 3.9 ml/100 ml forearm per min for the six incremental adenosine dosages, respectively. After the intravenous draflazine infusion, these values were 1.6 +/- 0.2 ml/100 ml forearm per min for placebo and 2.1 +/- 0.3, 3.3 +/- 0.6, 5.8 +/- 1.1, 6.9 +/- 1.4, 14.4 +/- 2.9, and 23.5 +/- 4.0 ml/100 ml forearm per min, respectively (Friedman ANOVA: P < 0.05 before vs after draflazine infusion). In conclusion, a 30-50% inhibition of adenosine transport significantly augments the forearm vasodilator response to adenosine without significant systemic effects. These results suggest that draflazine is a feasible tool to potentiate adenosine mediated cardioprotection in man. PMID- 7860750 TI - Insulin secretion, insulin action, and hepatic glucose production in identical twins discordant for non-insulin-dependent diabetes mellitus. AB - 12 identical twin pairs discordant for non-insulin-dependent diabetes mellitus (NIDDM) were studied for insulin sensitivity (euglycemic insulin clamp, 40 mU/m2 per min), hepatic glucose production (HGP, [3-3H]glucose infusion), and insulin secretion (oral glucose tolerance test and hyperglycemic [12 mM] clamp, including glucagon administration). Five of the nondiabetic twins had normal and seven had impaired glucose tolerance. 13 matched, healthy subjects without a family history of diabetes were included as control subjects. The NIDDM twins were more obese compared with their non-diabetic co-twins. The nondiabetic twins were insulin resistant and had a delayed insulin and C-peptide response during oral glucose tolerance tests compared with controls. Furthermore, the nondiabetic twins had a decreased first-phase insulin response and a decreased maximal insulin secretion capacity during hyperglycemic clamping and intravenous glucagon administration. Nondiabetic twins and controls had similar rates of HGP. Compared with both nondiabetic twins and controls, the NIDDM twins had an elevated basal rate of HGP, a further decreased insulin sensitivity, and a further impaired insulin secretion pattern as determined by all tests. In conclusion, defects of both in vivo insulin secretion and insulin action are present in non- and possibly prediabetic twins who possess the necessary NIDDM susceptibility genes. However, all defects of both insulin secretion and glucose metabolism are expressed quantitatively more severely in their identical co-twins with overt NIDDM. PMID- 7860751 TI - A unique ectonucleotide pyrophosphohydrolase associated with porcine chondrocyte derived vesicles. AB - Previous studies have shown increased nucleotide pyrophosphohydrolase (EC 3.6.1.8) (NTPPHase) activity in detergent extracts of degenerated human cartilage containing calcium pyrophosphate dihydrate (CPPD) crystals relative to those from osteoarthritis or normal cartilage. NTPPHase was later shown to be an ectoenzyme and its activity was increased in synovial fluid from patients with CPPD crystal deposits relative to fluids from other types of arthritis. We have purified a soluble 61-kD NTPPHase from conditioned media of organ-cultured porcine articular cartilage to electrophoretic homogeneity. Its NH2-terminal sequence through 26 cycles showed < 30% homology to any previously reported protein sequence. An antibody raised to a synthetic peptide corresponding to this sequence reacted with denatured but not native enzyme. This antibody reacted against a sedimentable vesicle-associated 127-kD protein in conditioned media from cultured articular cartilage or from chondrocytes in primary monolayer culture and against a series of soluble proteins in conditioned media supernatant, including a 61-kD protein representing our original isolate. No reactivity was found in 1% SDS extracts of washed cultured chondrocytes, although these contained greater NTPPHase activity than the conditioned media. Antibody to PC-1, another ectoNTPPHase, reacted with 1% SDS extracts of whole chondrocytes but not against those chromatographic fractions containing the major portion of NTPPHase activity. Release of the vesicle-associated 127-kD enzyme into conditioned medium was stimulated three- to sevenfold by TGF beta 1. The antibody also reacted with a series of soluble proteins and with 127-kD sedimentable protein in human synovial fluid. Kinetic studies supported the existence of a unique vesicle associated NTPPHase; apparent Km (mM) of chondrocyte membrane NTPPHase was 1.5 and 3.0 at pH 7.3 and 9.88, respectively; apparent Km (mM) of vesicle associated NTPPHase was 0.83 and 1.28 at pH 7.3 and 9.88. The data suggest the existence of a unique ecto-NTPPHase associated with vesicles derived from normal articular cartilage. PMID- 7860752 TI - Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase. A potential mechanism for the hypolipidemic action of fibrates. AB - Epidemiological and transgenic animal studies have implicated apo C-III as a major determinant of plasma triglyceride metabolism. Since fibrates are very efficient in lowering triglycerides, it was investigated whether fibrates regulate apo C-III gene expression. Different fibrates lowered rat liver apo C III mRNA levels up to 90% in a dose- and time-dependent manner, whereas intestinal apo C-III mRNA remained constant. This decrease in liver apo C-III mRNA was rapid (1 d) and reversible, since it was restored to control levels within 1 wk after cessation of treatment. In addition, fenofibrate treatment abolished the developmental rise of hepatic apo C-III mRNA observed during the suckling-weaning period. Administration of fibrates to rats induced liver and intestinal expression of the acyl CoA oxidase gene, the rate-limiting enzyme for peroxisomal beta-oxidation of fatty acids. In primary cultures of rat and human hepatocytes, fenofibric acid lowered apo C-III mRNA in a time- and dose-dependent manner. This reduction in apo C-III mRNA levels was accompanied by a decreased secretion of apo C-III in the culture medium of human hepatocytes. In rat hepatocytes fenofibric acid induced acyl CoA oxidase gene expression, whereas acyl CoA oxidase mRNA remained unchanged in human hepatocytes. Nuclear run-on and transient transfection experiments of a reporter construct driven by the human apo C-III gene promoter indicated that fibrates downregulate apo C-III gene expression at the transcriptional level. In conclusion, these studies demonstrate that fibrates decrease rat and human liver apo C-III gene expression. In humans the mechanisms appears to be independent of the induction of peroxisomal enzymes. This downregulation of liver apo C-III gene expression by fibrates may contribute to the hypotriglyceridemic action of these drugs. PMID- 7860753 TI - Bacterial lipopolysaccharide-mediated fetal death. Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide. AB - Maternal infection is a cause of spontaneous abortion and preterm labor in humans, but the pathophysiology is unclear. We hypothesized that eicosanoids play an important role in infection-driven pregnancy loss. To investigate this hypothesis, we administered lipopolysaccharide (LPS) to pregnant C3H/HeN mice and found that LPS administration caused fetal death in a dose-dependent fashion. Pretreatment with indomethacin significantly decreased the proportion of fetal death from 83% to < 25% in mice injected with 10 micrograms of LPS. Also, decidual explants from LPS-treated mice produced significantly more inflammatory eicosanoids, including prostaglandins E2 and F2 alpha and thromboxane B2, than controls. We investigated the regulatory mechanisms responsible for increased decidual prostanoid production in response to LPS. Western and Northern blots demonstrated that decidual protein and mRNA levels of a recently recognized highly inducible form of cyclooxygenase, COX-2, were substantially increased in mice treated with LPS. Induction of COX-2 was rapid: mRNA was detected 30 min after LPS injection. In contrast, another form of cyclooxygenase, COX-1, was only minimally induced in response to LPS. Our data indicate that LPS induces decidual prostanoid production via increased COX-2 expression. Since LPS-mediated fetal death is markedly diminished by pretreatment with indomethacin, COX-2-mediated eicosanoid production is likely a key pathophysiologic event in LPS-mediated fetal death. PMID- 7860754 TI - Vertical Transmission of HIV-1. Correlation with maternal viral load and plasma levels of CD4 binding site anti-gp120 antibodies. AB - Almost all childhood HIV-1 is now acquired through vertical transmission. Identifying factors that affect the rate of transmission may lead to the initiation of specific preventive strategies. In this study, antibody levels against different neutralizing epitopes on the envelope glycoprotein of HIV-1 (gp120) were measured in HIV-1-infected pregnant women that either transmitted HIV-1 to their infants (18 women) or did not (29 women). Differences in levels of antibodies directed against the monomeric gp120 molecule and against the V3 loop region of gp120 were not significantly different between the two groups studied. However, significant differences were observed in the levels of CD4 binding site antibodies, as determined by the ability of diluted maternal plasma to inhibit binding of the CD4 binding site monoclonal antibody F105 (mAb F105) to monomeric gp120. In addition, more nontransmitting mothers had low viral load as defined by having two or more negative HIV-1 viral cultures during pregnancy compared with transmitters. This pilot study suggests that in addition to higher viral load, low levels of CD4 binding site antibodies correlate with increased risk of HIV-1 vertical transmission. Passive immunotherapy with broadly neutralizing CD4 binding site antibodies should be considered as a strategy to reduce this risk. PMID- 7860755 TI - Endothelial cell tolerance to hypoxia. Potential role of purine nucleotide phosphates. AB - The ability of cells to tolerate hypoxia is critical to their survival, but varies greatly among different cell types. Despite alterations in many cellular responses during hypoxic exposure, pulmonary arterial endothelial cells (PAEC) retain their viability and cellular integrity. Under similar experimental conditions, other cell types, exemplified by renal tubular epithelial cells, are extremely hypoxia sensitive and are rapidly and irreversibly damaged. To investigate potential mechanisms by which PAEC maintain cellular and functional integrity under these conditions, we compared the turnover of adenine and guanine nucleotides in hypoxia tolerant PAEC and in hypoxia-sensitive renal tubular endothelial cells under various hypoxic conditions. Under several different hypoxic conditions, hypoxia-tolerant PAEC maintained or actually increased ATP levels and the percentage of these nucleotides found in the high energy phosphates, ATP and GTP. In contrast, in hypoxia-sensitive renal tubular endothelial cells, the same high energy phosphates were rapidly depleted. Yet, in both cell types, there were minor alterations in the uptake of the precusor nucleotide and its incorporation into the appropriate purine nucleotide phosphates and marked decreases in ATPase and GTPase activity. This maintenance of high energy phosphates in hypoxic PAEC suggests that there exists tight regulation of ATP and GTP turnover in these cells and that preservation of these nucleotides may contribute to the tolerance of PAEC to acute and chronic hypoxia. PMID- 7860756 TI - Cloning and molecular characterization of the ontogeny of a rat ileal sodium dependent bile acid transporter. AB - Sodium-dependent bile acid transport in the rat ileum is abruptly expressed at weaning. Degenerate oligonucleotides, based on amino acid sequence identities between the rat liver and hamster ileal transporters, were used to amplify a rat ileal probe. A 1.2-kb cDNA clone, which contains the full coding region (348 amino acids, 38 kD), was isolated by hybridization screening. In vitro translation yielded a 38-kD protein which glycosylated to 48 kD. Sodium-dependent uptake of taurocholate was observed in oocytes injected with cRNA. Northern blot analysis revealed a 5.0-kb mRNA in ileum, kidney, and cecum. A 48-kD protein was detected in ileal brush border membranes and localized to the apical border of villus ileal enterocytes. mRNA and protein expression, which were negligible before weaning, increased dramatically at weaning. Nuclear transcription rates for the transporter increased 15-fold between postnatal days 7 and 28. The apparent molecular weight of the transporter also increased between days 19 and 28. In summary, the developmental regulation of the rat ileal sodium-dependent bile acid cotransporter is characterized by transcriptionally regulated increases in mRNA and protein levels at the time of weaning with changes in apparent molecular weight of the protein after weaning. PMID- 7860757 TI - The effects of non-insulin-dependent diabetes mellitus on the kinetics of onset of insulin action in hepatic and extrahepatic tissues. AB - The mechanism(s) of insulin resistance in non-insulin-dependent diabetes mellitus remains ill defined. The current studies sought to determine whether non-insulin dependent diabetes mellitus is associated with (a) a delay in the rate of onset of insulin action, (b) impaired hepatic and extrahepatic kinetic responses to insulin, and (c) an alteration in the contribution of gluconeogenesis to hepatic glucose release. To answer these questions, glucose disappearance, glucose release, and the rate of incorporation of 14CO2 into glucose were measured during 0.5 and 1.0 mU/kg-1 per min-1 insulin infusions while glucose was clamped at approximately 95 mg/dl in diabetic and nondiabetic subjects. The absolute rate of disappearance was lower (P < 0.05) and the rate of increase slower (P < 0.05) in diabetic than nondiabetic subjects during both insulin infusions. In contrast, the rate of suppression of glucose release in response to a change in insulin did not differ in the diabetic and nondiabetic subjects during either the low (slope 30-240 min:0.02 +/- 0.01 vs 0.02 +/- 0.01) or high (0.02 +/- 0.00 vs 0.02 +/- 0.00) insulin infusions. However, the hepatic response to insulin was not entirely normal in the diabetic subjects. Both glucose release and the proportion of systemic glucose being derived from 14CO2 (an index of gluconeogenesis) was inappropriately high for the prevailing insulin concentration in the diabetic subjects. Thus non-insulin-dependent diabetes mellitus slows the rate-limiting step in insulin action in muscle but not liver and alters the relative contribution of gluconeogenesis and glycogenolysis to hepatic glucose release. PMID- 7860758 TI - Glucose-induced alterations of cytosolic free calcium in cultured rat tail artery vascular smooth muscle cells. AB - We have previously suggested that hyperglycemia per se may contribute to diabetic hypertensive and vascular disease by altering cellular ion content. To more directly investigate the potential role of glucose in this process, we measured cytosolic free calcium in primary cultures of vascular smooth muscle cells isolated from Sprague-Dawley rat tail artery before and after incubation with 5 (basal), 10, 15, and 20 mM glucose. Glucose significantly elevated cytosolic free calcium in a dose- and time-dependent manner, from 110.0 +/- 5.4 to 124.5 +/- 9.0, 192.7 +/- 20.4, and 228.4 +/- 21.9 nM at 5, 10, 15, and 20 mM glucose concentrations, respectively. This glucose-induced cytosolic free calcium elevation was also specific, no change being observed after incubation with equivalent concentrations of L-glucose or mannitol. This glucose effect was also dependent on extracellular calcium and pH, since these calcium changes were inhibited in an acidotic or a calcium-free medium, or by the competitive calcium antagonist lanthanum. We conclude that ambient glucose concentrations within clinically observed limits may alter cellular calcium ion homeostasis in vascular smooth muscle cells. We suggest that these cellular ionic effects of hyperglycemia may underlie the predisposition to hypertension and vascular diseases among diabetic subjects and/or those with impaired glucose tolerance. PMID- 7860759 TI - In vivo gene therapy for hyperlipidemia: phenotypic correction in Watanabe rabbits by hepatic delivery of the rabbit LDL receptor gene. AB - Elevations of plasma total or LDL cholesterol are major risk factors for cardiovascular disease. Efforts directed at preventing and treating cardiovascular disease have often focused on reducing the levels of these substances in the blood. The Watanabe Heritable Hyperlipidemic Rabbit, which has exceedingly high plasma cholesterol levels resulting from an LDL receptor deficiency, provides an excellent animal model for testing new treatments. A recombinant adenoviral vector containing the rabbit LDL receptor cDNA was administered to Watanabe rabbits. Plasma total cholesterol levels in the treated animals were reduced from 825.5 +/- 69.8 (mean +/- SD) to 247.3 +/- 61.5 mg/dl 6 d after infusion. These animals also demonstrated a 300-400% increase in plasma levels of HDL cholesterol and apo AI 10 d after treatment. As a result, the LDL:HDL ratio exhibited a dramatic decrease. Because only the rabbit LDL receptor gene was used for treatment, the results strongly suggest that the elevations of plasma HDL cholesterol and apo AI were secondary to a reduction in plasma total cholesterol in the treated animals. These results suggest an inverse relationship between plasma LDL and HDL cholesterol levels and imply that reduction of LDL cholesterol levels may have a beneficial effect on plasma HDL cholesterol. PMID- 7860760 TI - Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein. AB - Mildly oxidized low density lipoprotein (MM-LDL) produced by oxidative enzymes or cocultures of human artery wall cells induces endothelial cells to produce monocyte chemotactic protein-1 and to bind monocytes. HDL prevents the formation of MM-LDL by cocultures of artery wall cells. Using albumin treatment and HPLC we have isolated and partially characterized bioactive oxidized phospholipids in MM LDL. Platelet activating factor-acetylhydrolase (PAF-AH), a serine esterase, hydrolyzes short chain acyl groups esterified to the sn-2 position of phospholipids such as PAF and particular oxidatively fragmented phospholipids. Treatment of MM-LDL with PAF-AH (2-4 x 10(-2) U/ml) eliminated the ability of MM LDL to induce endothelial cells to bind monocytes. When HDL protected against the formation of MM-LDL by cocultures, lysophosphatidylcholine was detected in HDL; whereas when HDL was pretreated with diisopropyl fluorophosphate, HDL was no longer protective and lysophosphatidylcholine was undetectable. HPLC analysis also revealed that the active oxidized phospholipid species in MM-LDL had been destroyed after PAF-AH treatment. In addition, treatment of MM-LDL with albumin removed polar phospholipids that, when reisolated, induced monocyte binding to endothelial cells. These polar phospholipids, when treated with PAF-AH, lost biological activity and were no longer detected by HPLC. These results suggest that PAF-AH in HDL protects against the production and activity of MM-LDL by facilitating hydrolysis of active oxidized phospholipids to lysolipids, thereby destroying the biologically active lipids in MM-LDL. PMID- 7860761 TI - Impaired net hepatic glycogen synthesis in insulin-dependent diabetic subjects during mixed meal ingestion. A 13C nuclear magnetic resonance spectroscopy study. AB - Hepatic glycogen concentration was measured in six subjects with insulin dependent diabetes mellitus (IDDM) and nine weight-matched control subjects using 13C nuclear magnetic resonance spectroscopy during a day in which three isocaloric mixed meals were ingested. The relative fluxes of the direct and indirect (3 carbon units-->-->glycogen) pathways of hepatic glycogen synthesis were also assessed using [1-13C]glucose in combination with acetaminophen to noninvasively sample the hepatic UDP-glucose pool. Mean fasting hepatic glycogen content was similar in the two groups. After each meal, hepatic glycogen content increased, peaking 4-5 h after the meal in both groups. By 11:00 p.m. the IDDM subjects had synthesized only 30% of the glycogen that was synthesized by the control group [IDDM subjects, net increment = 44 +/- 20 (mean +/- SE) mM; control subjects, net increment = 144 +/- 14 mM; P < 0.05]. After breakfast the flux through the gluconeogenic pathway relative to the direct pathway of hepatic glycogen synthesis was 1.7-fold greater in the IDDM subjects (59 +/- 4%) than in the control subjects (35 +/- 4%, P < 0.0003). In conclusion, under mixed meal conditions, subjects with poorly controlled IDDM have a major defect in net hepatic glycogen synthesis and augmented hepatic gluconeogenesis. The former abnormality may result in an impaired glycemic response to counterregulatory hormones, whereas both abnormalities may contribute to postprandial hyperglycemia. PMID- 7860762 TI - Human cerebral osmolytes during chronic hyponatremia. A proton magnetic resonance spectroscopy study. AB - The pathogenesis of morbidity associated with hyponatremia is postulated to be determined by the state of intracellular cerebral osmolytes. Previously inaccessible, these metabolites can now be quantitated by proton magnetic resonance spectroscopy. An in vivo quantitative assay of osmolytes was performed in 12 chronic hyponatremic patients (mean serum sodium 120 meq/liter) and 10 normal controls. Short echo time proton magnetic resonance spectroscopy of occipital gray and parietal white matter locations revealed dramatic reduction in the concentrations of several metabolites. In gray matter, myo-inositol was most profoundly reduced at 49% of control value. Choline containing compounds were reduced 36%, creatine/phosphocreatine 19%, and N-acetylaspartate 11% from controls. Similar changes were found in white matter. Recovery of osmolyte concentrations was demonstrated in four patients studied 8-14 wk later. These results are consistent with a reversible osmolyte reduction under hypoosmolar stress in the intact human brain and offer novel suggestions for treatment and monitoring of this common clinical event. PMID- 7860763 TI - Nitric oxide regulates the calcium current in isolated human atrial myocytes. AB - Cardiac Ca2+ current (ICa) was shown to be regulated by cGMP in a number of different species. Recently, we found that the NO-donor SIN-1 (3-morpholino sydnonimine) exerts a dual regulation of ICa in frog ventricular myocytes via an accumulation of cGMP. To examine whether NO also regulates Ca2+ channels in human heart, we investigated the effects of SIN-1 on ICa in isolated human atrial myocytes. An extracellular application of SIN-1 produced a profound stimulatory effect on basal ICa at concentrations > 1 pM. Indeed, 10 pM SIN-1 induced a approximately 35% increase in ICa. The stimulatory effect of SIN-1 was maximal at 1 nM (approximately 2-fold increase in ICa) and was comparable with the effect of a saturating concentration (1 microM) of isoprenaline, a beta-adrenergic agonist. Increasing the concentration of SIN-1 to 1-100 microM reduced the stimulatory effect in two thirds of the cells. The stimulatory effect of SIN-1 was not mimicked by SIN-1C, the cleavage product of SIN-1 produced after liberation of NO. This suggests that NO mediates the effects of SIN-1 on ICa. Because, in frog heart, the stimulatory effect of SIN-1 on ICa was found to be due to cGMP-induced inhibition of cGMP-inhibited phosphodiesterase (cGI-PDE), we compared the effects of SIN-1 and milrinone, a cGI-PDE selective inhibitor, on ICa in human. Milrinone (10 microM) induced a strong stimulation of ICa (approximately 150%), demonstrating that cGI-PDE controls the amplitude of basal ICa in this tissue. In the presence of milrinone, SIN-1 (0.1-1 nM) had no stimulatory effect on ICa, suggesting that the effects of SIN-1 and MIL were not additive. We conclude that NO may stimulate ICa in human atrial myocytes via inhibition of the cGI-PDE. PMID- 7860764 TI - Activation of Jun kinase is an early event in hepatic regeneration. AB - Compensatory hepatic regeneration after partial hepatectomy (PH) is dependent upon the extent of resection. This study analyzes the regulation of the AP-1 transcription factor c-Jun during hepatic regeneration. There is a progressive increase in c-jun mRNA levels after sham operation, one-third PH, and two-thirds PH. A concomitant increase in AP-1 binding activity is also observed. The c-Jun protein is a major constituent of the AP-1 complex in quiescent and early regenerating liver. The activity of c-Jun nuclear kinase (JNK), which phosphorylates the activation domain of the c-Jun protein, is markedly stimulated after one-third PH. JNK1 or an immunologically related kinase is a constituent of this stimulated JNK activity after PH. When primary cultures of adult rat hepatocytes are incubated with epidermal growth factor or transforming growth factor-alpha, AP-1 transcriptional activity is increased and the activation domain of the c-Jun protein is further potentiated. Phosphopeptide mapping of the endogenous c-Jun protein in proliferating cultured hepatocytes demonstrates phosphorylation of the c-Jun activation domain. Combining the results of these in vivo and culture studies, we conclude that the minimal stimulation of one-third PH activates JNK, which phosphorylates the c-Jun activation domain in hepatocytes, resulting in enhanced transcription of AP-1-dependent genes. PMID- 7860765 TI - Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle. AB - We have investigated the mechanisms of the anabolic effect of insulin on muscle protein metabolism in healthy volunteers, using stable isotopic tracers of amino acids. Calculations of muscle protein synthesis, breakdown, and amino acid transport were based on data obtained with the leg arteriovenous catheterization and muscle biopsy. Insulin was infused (0.15 mU/min per 100 ml leg) into the femoral artery to increase femoral venous insulin concentration (from 10 +/- 2 to 77 +/- 9 microU/ml) with minimal systemic perturbations. Tissue concentrations of free essential amino acids decreased (P < 0.05) after insulin. The fractional synthesis rate of muscle protein (precursor-product approach) increased (P < 0.01) after insulin from 0.0401 +/- 0.0072 to 0.0677 +/- 0.0101%/h. Consistent with this observation, rates of utilization for protein synthesis of intracellular phenylalanine and lysine (arteriovenous balance approach) also increased from 40 +/- 8 to 59 +/- 8 (P < 0.05) and from 219 +/- 21 to 298 +/- 37 (P < 0.08) nmol/min per 100 ml leg, respectively. Release from protein breakdown of phenylalanine, leucine, and lysine was not significantly modified by insulin. Local hyperinsulinemia increased (P < 0.05) the rates of inward transport of leucine, lysine, and alanine, from 164 +/- 22 to 200 +/- 25, from 126 +/- 11 to 221 +/- 30, and from 403 +/- 64 to 595 +/- 106 nmol/min per 100 ml leg, respectively. Transport of phenylalanine did not change significantly. We conclude that insulin promoted muscle anabolism, primarily by stimulating protein synthesis independently of any effect on transmembrane transport. PMID- 7860766 TI - Mechanisms of filtration failure during postischemic injury of the human kidney. A study of the reperfused renal allograft. AB - Postischemic filtration failure in experimental animals results primarily from depression of the transcapillary hydraulic pressure difference (delta P), a quantity that cannot be determined in humans. To circumvent this limitation we determined the GFR and each of its remaining determinants in transplanted kidneys. Findings in 12 allografts that exhibited subsequent normofiltration (group 1) were compared with those in 11 allografts that exhibited persistent hypofiltration (group 2). Determinations were made intraoperatively in the exposed graft after 1-3 h of reperfusion. GFR (6 +/- 2 vs 29 +/- 5 ml/min) and renal plasma flow by Doppler flow meter (140 +/- 30 vs 315 +/- 49 ml/min) were significantly lower in group 2 than group 1. Morphometric analysis of glomeruli obtained by biopsy and a structural hydrodynamic model of viscous flow revealed the glomerular ultrafiltration coefficient to be similar, averaging 3.5 +/- 0.6 and 3.1 +/- 0.2 ml/(min.mmHg) in group 2 vs 1, respectively. Corresponding values for plasma oncotic pressure were also similar, averaging 19 +/- 1 vs 21 +/- 1 mmHg. We next used a mathematical model of glomerular ultrafiltration and a sensitivity analysis to calculate the prevailing range for delta P from the foregoing measured quantities. This revealed delta P to vary from only 20-21 mmHg in group 2 vs 34-45 mmHg in group 1 (P < 0.001). Further morphometric analysis revealed the diameters of Bowman's space and tubular lumens, as well as the percentage of tubular cells that were necrotic or devoid of brush border, to be similar in the two groups. We thus conclude (a) that delta P depression is the predominant cause of hypofiltration in this form of postischemic injury; and (b) that afferent vasoconstriction rather than tubular obstruction is the proximate cause of the delta P depression. PMID- 7860767 TI - High levels of glucose-6-phosphatase gene and protein expression reflect an adaptive response in proliferating liver and diabetes. AB - The regenerating liver after partial hepatectomy is one of the few physiologic models of cellular proliferation in the adult animal. During hepatic regeneration, the animal is able to maintain metabolic homeostasis despite the acute loss of two thirds of hepatic tissue. In examining the molecular mechanisms regulating hepatic regeneration, we isolated novel immediate-early genes that are rapidly induced as the remnant liver undergoes the transition from its normal quiescent state into the G1 phase of the cell cycle. One of the most rapidly and highly induced genes which we initially termed RL-1, encodes rat glucose-6 phosphatase (rG6Pase). G6Pase mRNA peaks at 30 min and 36-48 h after hepatectomy correlating with the first and second rounds of cell division. This finding is compatible with studies that showed that G6Pase enzyme activity increases during liver regeneration. However, the increase in G6Pase mRNA is much more dramatic, indicating that it is a more sensitive indicator of this regulation. G6Pase gene expression peaks in the perinatal time period in the liver and remains elevated during the first month of life. The expression of the G6Pase gene is also dramatically elevated in BB diabetic rats, again higher than the enzyme elevation, and its relative induction after partial hepatectomy is blunted in these animals. Insulin treatment of partially hepatectomized diabetic animals downregulates the expression of G6Pase mRNA. Using specific antibodies against G6Pase, we detect a 36-kD G6Pase protein, and its level is elevated in regenerating and diabetic livers. The pattern of G6Pase mRNA expression appears to reflect similar changes in insulin and glucagon levels which accompany diabetes and hepatic proliferation. The elevation of G6Pase expression in these conditions is indicative of its importance as a regulator of glucose homeostasis in normal and abnormal physiologic states. PMID- 7860768 TI - Neu differentiation factor upregulates epidermal migration and integrin expression in excisional wounds. AB - Neu differentiation factor (NDF) is a 44-kD glycoprotein which was isolated from ras-transformed rat fibroblasts and indirectly induces tyrosine phosphorylation of the HER-2/neu receptor via binding to either the HER-3 or HER-4 receptor. NDF contains a receptor binding epidermal growth factor (EGF)-like domain and is a member of the EGF family. There are multiple different isoforms of NDF which arise by alternative splicing of a single gene. To date, in vivo biologic activities have not been demonstrated for any NDF isoform. Since NDF, HER-2/neu, and HER-3 are present in skin, and other EGF family members can influence wound keratinocytes in vivo, we investigated whether NDF would stimulate epidermal migration and proliferation in a rabbit ear model of excisional wound repair. In this model, recombinant human NDF-alpha 2 (rhNDF-alpha 2), applied once at the time of wounding, induced a highly significant increase in both epidermal migration and epidermal thickness at doses ranging from 4 to 40 micrograms/cm2. In contrast, rhNDF-alpha 1, rhNDF-beta 1, and rhNDF-beta 2 had no apparent biologic effects in this model. rhNDF-alpha 2 also induced increased neoepidermal expression of alpha 5 and alpha 6 integrins, two of the earliest integrins to appear during epidermal migration. In addition, rhNDF-alpha 2-treated wounds exhibited increased neoepidermal expression of cytokeratin 10 and filaggrin, both epidermal differentiation markers. NDF alpha isoforms were expressed in dermal fibroblasts of wounded and unwounded skin, while both HER-2/neu and HER-3 were expressed in unwounded epidermis and dermal adnexa. In wounds, HER-2/neu expression was markedly decreased in the wound neoepidermis while neoepidermal HER-3 expression was markedly upregulated. Taken together, these results suggest that endogenous NDF-alpha 2 may function as a paracrine mediator directing initial epidermal migration during cutaneous tissue repair. PMID- 7860769 TI - Immunopathological mechanisms of human T cell lymphotropic virus type 1 (HTLV-I) uveitis. Detection of HTLV-I-infected T cells in the eye and their constitutive cytokine production. AB - The immunopathology of human T cell lymphotropic virus type 1 (HTLV-I) uveitis was addressed by using T cell clones (TCC) established from the intraocular fluid of patients with HTLV-I uveitis. Proviral DNA of HTLV-I was identified in 55 out of 94 (59%) or 13 out of 36 (36%) TCC from the ocular fluid or the peripheral blood of these patients, respectively. Most of HTLV-I-infected TCC had a CD3+ CD4+ CD8- phenotype. HTLV-I infection on TCC was confirmed by analysis of the viral mRNA, nucleotide sequence, virus-associated proteins, and virus particles. HTLV-I-infected TCC, but not HTLV-I negative TCC, constitutively produced high amounts of IL-6 (1,336 +/- 1,050 pg/ml) and TNF-alpha (289 +/- 237 pg/ml) in the absence of any stimuli. HTLV-I-infected TCC from the ocular lesion also constitutively produced high amounts of IL-1 alpha (12,699 pg/ml), IL-2 (61 pg/ml), IL-3 (428 pg/ml), IL-8 (1,268 pg/ml), IL-10 (28 pg/ml), IFN-gamma (5,095 pg/ml), and GM-CSF (2,886 pg/ml). Hydrocortisone, a drug effective in vivo for the treatment of HTLV-I uveitis, severely depressed cytokine production in vitro in most cases. In summary, the results demonstrated direct evidence of HTLV-I infection of the eye and suggest that cytokines produced by HTLV-I-infected T cells are responsible for the intraocular inflammation in patients with HTLV-I uveitis. PMID- 7860770 TI - Expression of a mutant human fibrillin allele upon a normal human or murine genetic background recapitulates a Marfan cellular phenotype. AB - The Marfan syndrome (MFS) is a connective tissue disorder inherited as an autosomal dominant trait and caused by mutations in the gene encoding fibrillin, a 350-kD glycoprotein that multimerizes to form extracellular microfibrils. It has been unclear whether disease results from a relative deficiency of wild-type fibrillin; from a dominant-negative effect, in which mutant fibrillin monomers disrupt the function of the wild-type protein encoded by the normal allele; or from a dynamic and variable interplay between these two pathogenetic mechanisms. We have now addressed this issue in a cell culture system. A mutant fibrillin allele from a patient with severe MFS was expressed in normal human and murine fibroblasts by stable transfection. Immunohistochemical analysis of the resultant cell lines revealed markedly diminished fibrillin deposition and disorganized microfibrillar architecture. Pulse-chase studies demonstrated normal levels of fibrillin synthesis but substantially reduced deposition into the extracellular matrix. These data illustrate that expression of a mutant fibrillin allele, on a background of two normal alleles, is sufficient to disrupt normal microfibrillar assembly and reproduce the MFS cellular phenotype. This underscores the importance of the fibrillin amino-terminus in normal microfibrillar assembly and suggests that expression of the human extreme 5' fibrillin coding sequence may be sufficient, in isolation, to produce an animal model of MFS. Lastly, this substantiation of a dominant-negative effect offers mutant allele knockout as a potential strategy for gene therapy. PMID- 7860771 TI - Regulation of human bone marrow-derived osteoprogenitor cells by osteogenic growth factors. AB - Human bone marrow contains a distinct cell population that expresses bone proteins and responds to transforming growth factor beta 1 (TGF-beta), but not to hematopoietic growth factors (Long, M. W., J. L. Williams, and K. G. Mann. 1990. J. Clin. Invest. 86:1387-1395). We now report the isolation, characterization, and growth factor responsiveness of these precursors to human osteoblasts and the identification of a human osteoprogenitor cell. Immunological separation of human bone marrow nonadherent low-density (NALD) cells results in a marked enrichment of cells that express osteocalcin, osteonectin, and bone alkaline phosphatase. Flow cytometric analyses show that distinct cell subpopulations exist among these isolated cells. The majority of the bone antigen-positive cells are approximately the size of a lymphocyte, whereas other, less frequent antibody-separated subpopulations consist of osteoblast-like cells and osteoprogenitor cells. In serum-free cultures, TGF-beta stimulates the small, antigen-positive cells to become osteoblast-like, as these cells both increase in size, and express increased levels of osteocalcin and alkaline phosphatase. Antibody-separated cells also contain a separate population of clonal progenitor cells that form colonies of osteoblast-like cells when cultured in serum-free, semi-solid media. Two types of human osteoprogenitor cells are observed: a colony-forming cell (CFC) that generates several hundred bone antigen-positive cells, and a more mature cluster-forming cell that has a lesser proliferative potential and thus generates clusters of 20-50 antigen-positive cells. Osteopoietic colony-forming cells and cluster-forming cells have an obligate but differential requirement for osteogenic growth factors. The CFCs respond to TGF-beta, basic fibroblast growth factor (bFGF), bone morphogenic protein-2 (BMP-2), and 1, 25-dihydroxy vitamin D3 (1,25-OH D3). In contrast to the colony-forming cells, cluster-forming cells are regulated predominantly by 1,25-OH D3 and TGF-beta, but fail to respond to bFGF. We conclude that human bone marrow contains a nonhematogenous, heterogeneous population of bone precursor cells among which exists a population of proliferating osteoprogenitor cells. Further characterization of these bone precursor cell populations should yield important information on their role in osteogenesis in both health and disease. PMID- 7860772 TI - Differential regulation of two types of intracellular calcium release channels during end-stage heart failure. AB - The molecular basis of human heart failure is unknown. Alterations in calcium homeostasis have been observed in failing human heart muscles. Intracellular calcium-release channels regulate the calcium flux required for muscle contraction. Two forms of intracellular calcium-release channels are expressed in the heart: the ryanodine receptor (RyR) and the inositol 1,4,5-trisphosphate receptor (IP3R). In the present study we showed that these two cardiac intracellular calcium release channels were regulated in opposite directions in failing human hearts. In the left ventricle, RyR mRNA levels were decreased by 31% (P < 0.025) whereas IP3R mRNA levels were increased by 123% (P < 0.005). In situ hybridization localized both RyR and IP3R mRNAs to human cardiac myocytes. The relative amounts of IP3 binding sites increased approximately 40% compared with ryanodine binding sites in the failing heart. RyR down-regulation could contribute to impaired contractility; IP3R up regulation may be a compensatory response providing an alternative pathway for mobilizing intracellular calcium release, possibly contributing to the increased diastolic tone associated with heart failure and the hypertrophic response of failing myocardium. PMID- 7860773 TI - Female germ line mosaicism as the origin of a unique IL-2 receptor gamma-chain mutation causing X-linked severe combined immunodeficiency. AB - The IL2RG gene encoding the gamma chain of the lymphocyte receptor for IL-2 lies in human Xq13.1 and is mutated in males with X-linked severe combined immunodeficiency (SCID). In a large Canadian pedigree genetic linkage studies demonstrated that the proband's grandmother was the source of an X-linked SCID mutation. However, her T cells did not show the expected skewed X chromosome inactivation pattern of female carriers of SCID, despite her having one affected son and two carrier daughters with skewed X inactivation. Single strand conformation polymorphism analysis of IL2RG in the affected proband was abnormal in exon 5; sequencing revealed a nine nucleotide in-frame duplication insertion. The three duplicated amino acids included the first tryptophan of the "WSXWS" motif found in all members of the cytokine receptor gene superfamily. Mutation detection in the pedigree confirmed that the founder grandmother's somatic cells had only normal IL2RG, and further showed that the SCID-associated X chromosome haplotype was inherited by three daughters, one with a wild type IL2RG gene and two others with the insertional mutation. Female germ line mosaicism is unusual, but its presence in this X-linked SCID family emphasizes the limitations of genetic diagnosis by linkage as compared with direct mutation analysis. PMID- 7860774 TI - Cell density and paradoxical transcriptional properties of c-Myc and Max in cultured mouse fibroblasts. AB - Deregulated expression of the c-Myc oncoprotein occurs in several human malignancies. The c-Myc protein behaves as a transcription factor, and undoubtedly its role in carcinogenesis involves its ability to affect the expression of genes involved in cell growth. c-Myc has been reported to both activate and repress transcription in transient transfection experiments using reporter constructs bearing multiple copies of the c-Myc binding site, CAC (G/A) TG. We investigated these apparently paradoxical effects of c-Myc by determining if they arose from differences in the cell proliferation states of transfected cells. We found that endogenous c-Myc protein levels vary inversely with the degree of cell confluency, such that at low cell confluency, where endogenous levels of c-Myc are high and presumably endogenous levels of Max are limiting, exogenous c-Myc fails to affect basal transcription. In cells at high cell confluency, in which endogenous c-Myc levels are low, exogenous c-Myc augments transactivation by titrating the relative excess endogenous Max. These observations suggest that the apparently paradoxical behavior of c-Myc in transfection experiments is partially dependent on ambient cellular levels of c Myc. PMID- 7860775 TI - Congenital erythropoietic porphyria: identification and expression of 10 mutations in the uroporphyrinogen III synthase gene. AB - To investigate the molecular basis of the phenotypic heterogeneity in congenital erythropoietic porphyria, the mutations in the uroporphyrinogen III synthase gene from unrelated patients were determined. Six missense (L4F, Y19C, V82F, V99A, A104V, and G225S), a nonsense (Q249X), a frameshift (633insA), and two splicing mutations (IVS2+1 and IVS9 delta A + 4) were identified. When L4F, Y19C, V82F, V99A, A104V, 633insA, G225S, and Q249X were expressed in Escherichia coli, only the V82F, V99A, and A104V alleles expressed residual enzymatic activity. Of note, the V82F mutation, which occurs adjacent to the 5' donor site of intron 4, resulted in approximately 54% aberrantly spliced transcripts with exon 4 deleted. Thus, this novel exonic single-base substitution caused two lesions, a missense mutation and an aberrantly spliced transcript. Of the splicing mutations, the IVS2+1 allele produced a single transcript with exon 2 deleted, whereas the IVS9 delta A+4 allele was alternatively spliced, approximately 26% being normal transcripts and the remainder with exon 9 deleted. The amount of residual activity expressed by each allele provided a basis to correlate genotype with disease severity, thereby permitting genotype/phenotype predictions in this clinically heterogeneous disease. PMID- 7860776 TI - Projections from the lateral and interposed cerebellar nuclei to the thalamus of the rat: a light and electron microscopic study using single and double anterograde labelling. AB - The lateral and interposed cerebellar nuclei may have different functions in the control of movement. Efferent fibres from both nuclei project predominantly to areas of the thalamus, which in turn project to the motor cortex. In this study, single and double anterograde-tracing techniques have been used to examine and compare the pathways from the lateral and interposed nuclei to the thalamus in the rat by using both light and electron microscopy to look for evidence of organisational or structural features that may underlie the proposed functional differences between these nuclei. Terminals from the lateral nucleus were found to be located most medially in the thalamus, predominantly in the ventral lateral nucleus and the rostral pole of the posterior nuclear group. Terminals from the posterior interposed nucleus were located slightly rostral and lateral to those from the lateral nucleus, mainly around the border between the ventral lateral nucleus and the ventral posterior medial nucleus. Terminals from the anterior interposed nucleus were located slightly rostral and lateral to those from the posterior interposed nucleus, predominantly in the rostral pole of the ventral posterior lateral nucleus. Terminals from the lateral and interposed nuclei were also found in double anterograde-tracing experiments to be nonoverlapping in the regions between these main areas of termination. The structure of terminals from the lateral and interposed nuclei, however, as well as their synaptic relationship with thalamic neurones, were found to be similar. The terminals are large and form synapses with proximal dendrites of thalamic neurones. They contained round vesicles and formed multiple synaptic contacts with dendritic shafts, as well as dendritic spines. The findings indicate that information from the lateral and interposed nuclei is processed in separate regions of the thalamus but that the mode of synaptic transfer to thalamic neurones is likely to be similar for the two projections. PMID- 7860777 TI - Analysis of gamma-aminobutyric acidergic synaptic contacts in the thalamic reticular nucleus of the monkey. AB - Gamma-aminobutyric acidergic (GABAergic) neurons in the thalamic reticular nucleus (TRN) spontaneously generate a synchronous bursting rhythm during slow wave sleep in most mammals. A previous study at the electron microscopic level in cat anterior TRN has suggested that synchronous bursting activity could result from the large number of presumably GABAergic dendrodendritic synaptic contacts. However, little is known about the synaptology of the monkey thalamic reticular nucleus and whether it contains dendrodendritic contacts. To address this issue, we examined tissue obtained from Macaca fascicularis that was prepared for electron microscopy using postembedding techniques to demonstrate GABA immunoreactivity. Examination of the anterior (motor) and posterior (somatosensory) portions of the TRN disclosed the following: The majority of synaptic contacts (87.5% of 958) were formed by axon terminals showing no GABA immunoreactivity and making asymmetric synaptic contacts on dendrites or cell bodies. A further 6.4% of synaptic contacts was composed of GABA-immunoreactive presynaptic terminals making symmetric contacts with the dendrites of TRN neurons. The majority resembled the pleomorphic vesicle containing F-terminals seen in the dorsal thalamus and known to originate from axons of TRN. A subset or possible second class did not resemble any previously described class of GABA immunoreactive terminals in the TRN. Both classes of these terminals making symmetric contacts may originate wholly or partially within the nucleus. There was one dendrodendritic synaptic contact and only a small number (3.2%) of axodendritic contacts with synaptic vesicles visible both pre- and postsynaptically. We conclude that dendrodendritic contacts are probably not responsible for the synchronized bursting neuronal activity seen in the slow-wave sleep of monkeys, and that, if TRN neurons are coupled synaptically, the most likely mechanism is through the synapses formed by recurrent axon collaterals of TRN neurons onto TRN dendrites. PMID- 7860778 TI - Distribution of calcium-binding protein calbindin-D28k in the auditory system of adult and developing rats. AB - Calbindin-D28k (CaBP) is a calcium-binding protein, which appears to be involved in the buffering of free intracellular calcium and may thereby contribute to calcium homeostasis. This study attempted to determine the distribution pattern of CaBP immunoreactivity in the central auditory system of adult rats and during development, when calcium ions play key roles in several aspects of nerve cell function. It was found that most steps during CaBP development occur postnatally in the central auditory system. With the exception of the lateral superior olive, the ventral and the intermediate nuclei of the lateral lemniscus, and the auditory cortex, which already express CaBP prenatally, CaBP immunoreactivity is not present before postnatal day 2 (P2). Development proceeds until about P24, when the pattern characteristic of adult animals can be seen. There was no detectable sequence in CaBP development from lower to higher stations in the auditory pathway, i.e., the different nuclei appear to express CaBP independently of each other, indicating that intrinsic, rather than peripheral, maturation processes may predominantly influence CaBP expression. Neurons in four brainstem nuclei (the lateral superior olive, the ventral and intermediate nuclei of the lateral lemniscus, and the central nucleus of the inferior colliculus) express CaBP only transiently. In these nuclei, CaBP immunoreactivity peaks between P6 and P18, which coincides with the period of synapse stabilization. Therefore, CaBP may play a specific role during neuronal development, by buffering the concentration of intracellular free Ca2+, which may be necessary for modification of synaptic efficiency. PMID- 7860779 TI - Abdominal surgery induces Fos immunoreactivity in the rat brain. AB - Previous neuropharmacological studies indicate that brain peptides are involved in mediating gastric stasis induced by abdominal surgery. Central pathways activated by abdominal surgery were investigated in the rat by using Fos protein as a marker of neuronal activation. Abdominal surgery (laparotomy alone or combined with cecal manipulation) was performed under brief enflurane anesthesia (7-8 minutes), and 1 hour later rats were killed and brains processed for Fos immunoreactivity. Double labeling with Fos and arginine vasopressin, oxytocin, or tyrosine hydroxylase antibodies was also performed. Abdominal surgery induced Fos staining in the nucleus tractus solitarii, paraventricular and supraoptic nuclei of the hypothalamus, locus coeruleus, and ventrolateral medulla. After abdominal surgery, 18-25% of vasopressin and 18-33% of oxytocin-labeled cells were found to be Fos positive in the paraventricular nucleus and 15% of activated cells in the nucleus tractus solitarii were positive for tyrosine hydroxylase immunoreactivity. Enflurane alone induced c-fos expression in the same brain area; however, the number of Fos-positive cells and double-labeled cells were decreased two- to fivefold and three- to eightfold, respectively, compared with the abdominal surgery groups. These data show that abdominal surgery induced activation of specific hypothalamic, pontine, and medullary neurons. These findings may have implications for the understanding of central mechanisms involved in mediating gastric ileus following abdominal surgery. PMID- 7860780 TI - Postnatal development of [D-Ala2]deltorphin-I-like immunoreactive structures in the rat brain. AB - [D-Ala2]deltorphin-I, a highly selective ligand for delta opioid receptors, is a heptapeptide originally purified from frog skin. Previous immunohistochemical studies indicate that [D-Ala2]deltorphin-I-like molecule(s) may be present in adult rat brain, including specific neuronal cells and fibers partially overlapping with the mesocortical and nigrostriatal dopaminergic systems. Here, we examined the developmental aspect of such immunoreactive brain structures in early postnatal rats. In newborn to 21-day-old rats, positive staining in the brain occurred mainly in subpopulations of neurons and occasionally in tanycytes. On postnatal day 0, neuronal cell bodies containing [D-Ala2]deltorphin-I-like immunoreactivity were found in various brain regions, including the olfactory tubercle, ventral pallidum, hippocampus, ventral tegmental area, pars compacta of the substantia nigra, supramammillary nucleus, and dorsal raphe nucleus. Immunoreactive nerve fibers were observed in the main and accessory olfactory bulbs, olfactory tubercle, prelimbic area, anterior cingulate cortex, neostriatum, accumbens, lateral septal nucleus, lateral habenular nucleus, and superior colliculus. As pups grew, positive staining of cell bodies decreased gradually in both density and intensity, and those in the olfactory tubercle and ventral pallidum were no longer visible on postnatal day 14. On postnatal day 21, positive cells were found only in the ventral midbrain, including the pars compacta of the substantia nigra, ventral tegmental area, A8 region, and supramammillary nucleus. Positive fibers also decreased in density with age except in the accessory olfactory bulb, olfactory tubercle, prelimbic area, and anterior cingulate cortex. PMID- 7860781 TI - Paraventriculospinal tract as a model for axon injury: spinal cord. AB - The response of immunocytochemically identified hypothalamic axons innervating the rat spinal cord was examined at varying times after cord hemisection in a model of axonal injury using the paraventriculospinal projection. The purpose was to determine whether these long descending peptidergic axons would show signs of regrowth after injury. From 1 to 180 days after hemisection, horizontal sections of the spinal cord were stained with peroxidase immunocytochemistry. Antiserum against neurophysin was used to identify axons projecting from the hypothalamic paraventricular nucleus to the spinal cord. The paraventricular nucleus innervates all rostrocaudal segments of the cord, yet the projection is not massive, allowing the trauma response of individual axons to be studied. Immediately caudal to a T4 hemisection, axons began decreasing in number by 2 days after surgery. Ten days postoperatively, only a few axons could be found caudal to the cut; these remaining axons arose from the contralateral cord. A substantial increase in the number of stained axons was found rostral to the hemisection 3-12 weeks after surgery. In that an increase in axon number could be due to both increasing staining efficacy and sprouting, the orientation of axons in control and hemisected rats was studied. Three millimeters rostral to the hemisection, axons had a greater variance in orientation and were more likely to project medially out of the dorsolateral white matter compared with the contralateral control side. Rostral to the hemisection, a statistically significant two- to fourfold increase in the number of branches per axons was found in comparison to the contralateral control side. Axons were found in the dorsal white matter 4 months after surgery; in controls, immunostained axons were not found here. At all intervals after surgery, structures suggestive of growth were found, including terminal growth cones and lateral filopodia and lamellipodia extending from axons whose distal ends had been severed by hemisection. Similar structures were not found in control spinal cord. Together, these data suggest that after cord hemisection, axons from the paraventricular nucleus sprout rostral to the injury. PMID- 7860782 TI - Quantitative electron microscopic analysis of synaptic input from cortical areas 17 and 18 to the dorsal lateral geniculate nucleus in cats. AB - Cortical feedback is the largest extraretinal projection to the lateral geniculate nucleus. This input is thought to modulate the transfer of visual information in a state-dependent manner. The quantitative distribution and synaptology of axon terminals arising from different cortical areas is still an unsolved question. To address this problem, the synaptic termination pattern of corticogeniculate axons from cortical areas 17 and 18 entering the lateral geniculate nucleus of the cat was examined. The Phaseolus vulgaris leucoagglutinin anterograde tract tracing method was used for the labeling of corticogeniculate terminals. Postsynaptic targets were characterized by postembedding gamma-aminobutyric acid (GABA) immunocytochemistry. In both laminae A and A1, labeled corticogeniculate axons from area 17 established synaptic contacts with GABA-immunopositive, interneuronal dendritic profiles more frequently (17.5% of all axons) than did labeled axon terminals from area 18 (7% of axons). Conversely, 76% of labeled corticogeniculate axons from area 17, as opposed to 87% of labeled axons from area 18, terminated on GABA-immunonegative relay cell dendrites. Furthermore, the mean diameter of GABA-negative relay cell dendrites postsynaptic to labeled axons from area 17 was significantly smaller than the diameter of relay cell dendrites synapsing with labeled terminals from area 18. These results indicate that the corticogeniculate axons from cortical areas 17 and 18 exhibit different synaptic termination patterns in the dorsal lateral geniculate nucleus of the cat, suggesting that these two projections may subserve different functions in visual information processing. PMID- 7860783 TI - Morphological analysis of external urethral and external anal sphincter motoneurones of cat. AB - A previous electrophysiological study suggested that there is a common correlation among axonal conduction velocity, input resistance, and size of motoneurones regardless of the muscle type innervated by a motoneurone and that the dendritic arborization is less developed in sphincter than in hindlimb motoneurones. To verify the previous suggestions, cell bodies, axons, and dendrites of external urethral sphincter (EUS) and external anal sphincter (EAS) motoneurones were studied after intracellular labelling with horseradish peroxidase in cats anaesthetised with pentobarbitone. All the cell bodies were located in Onuf's nucleus. The soma diameter (19.7-50.0 microns) was positively correlated with the axonal conduction velocity, and the plots of these two variables were extrapolations from similar plots obtained for hindlimb alpha motoneurones, supporting the suggestion of the preceding report. Half of motoneurones had recurrent axon collaterals, which terminated within Onuf's nucleus and the ventral border of lamina VIII. The diameter of the cell body with collaterals was significantly larger than that without collaterals. Dendrites extended in five directions: dorsal, medial, lateral, rostral, and caudal. Dorsally directed dendrites of both EUS and EAS motoneurones coursed in lamina VII toward the intermediolateral nucleus, and dendrites of EAS motoneurones further extended toward the intermediomedial nucleus. Long dendrites directed rostrally or caudally within Onuf's nucleus, more prominently in EUS motoneurones. EAS motoneurones had longer end branches and relatively larger number of end branches and summed length and surface area of a dendrite compared with EUS. Among relations, the dendritic surface area and the dendritic volume were tightly correlated with the diameter of the first-order dendrite. The latter relation was almost identical between EUS, EAS, and hindlimb alpha- and gamma motoneurones. The large values for the dendritic-to-soma surface area ratio (31 in EUS, 50 in EAS) indicated the well-developed dendritic arborization comparable to hindlimb motoneurones. The ratio of sum sigma (daughter diameter)3/2 to the 3/2 power of the parent diameter was 0.99 in EUS and 1.08 in EAS motoneurones, indicating that the 3/2 power constraint at branching points is well satisfied, and Rall's equivalent-cylinder model is applicable to sphincter motoneurones. PMID- 7860784 TI - Developmental plasticity of reticulospinal and vestibulospinal axons in the north American opossum, Didelphis virginiana. AB - We have shown previously that rubral axons grow around a lesion of their spinal pathway in the North American opossum if it is made at early stages of development. In the present experiments, we have asked whether reticular and vestibular axons have the same ability. The spinal cord was hemisected at postnatal day 20, 12, or 5, well within the critical period for rubrospinal plasticity, and, approximately 30 days later, bilateral injections of fast blue were made about four segments caudal to the lesion. The pups were killed 4 or 5 days after the injections. In most of the animals lesioned on postnatal day 20, labeled neurons were not found in the medial part of the pontine reticular nucleus or the dorsal part of the lateral vestibular nucleus ipsilateral to the lesion. The spinal projections from both areas are exclusively ipsilateral. When the lesions were made at postnatal day 12 or 5, however, labeled neurons were present in both areas, suggesting that they supported axons that had grown caudal to the lesion. As was expected from previous studies, rubral neurons were labeled contralateral to the lesion in all three groups. In the opossum, as in other species, the red nucleus projects contralaterally. We conclude that reticular and vestibular axons, like axons from the red nucleus, grow around a lesion of their pathway during development and that the critical period for their plasticity ends earlier than that for rubrospinal axons. PMID- 7860785 TI - Glial domains and axonal reordering in the chiasmatic region of the developing ferret. AB - This study has examined the developing glial architecture of the optic pathway and has related this to the changing organization of the constituent axons. Immunocytochemistry was used to reveal the distribution of glial profiles, and DiI was used to label either radial glial profiles or optic axons. Electron microscopy was used to determine the distribution of glial profiles, axons, growth cones, and wrists at different locations along the pathway. Three different glial boundaries were defined: Two of these are revealed as changes in the distribution of vimentin-immunoreactive profiles occurring in the prechiasmatic optic nerve and at the threshold of the optic tract, respectively, and one by the presence of glial fibrillary acidic protein (GFAP)-immunoreactive profiles at the chiasmatic midline. The latter, midline boundary may be related to the segregation of nasal from temporal optic axons. The boundary at the threshold of the optic tract coincides with the segregation of dorsal from ventral optic axons that emerges at this location in the pathway. The segregation of old from young optic axons is shown to occur only gradually along the pathway. Glial profiles are most frequent in the deeper parts of the tract, coursing parallel to the optic axons and orthogonal to their usual radial axis. These are suggested to arise from later-growing radial glial fibers that are diverted to grow amongst the older optic axons. Those glial profiles may subsequently impede axonal invasion, thus creating the chronotopic reordering by forcing the later arriving axons to accumulate superficially. PMID- 7860786 TI - A quantitative analysis of parvalbumin neurons in rabbit auditory neocortex. AB - Parvalbumin (PV) is a calcium-binding protein present in GABAergic cells in the cerebral cortex and in thalamic relay neurons. In the present study, parvalbumin immunocytochemistry (PVi) and stereological methods were used to obtain estimates of cortical volume, total neuron number, laminar density, and the percentage of PV-immunoreactive neurons in auditory neocortex. PVi clearly delineated the primary auditory cortex (AI), which was characterized by two PV+ bands: dense terminal-like labeling within lamina III/IV and PV+ somata in lamina VIa. Stereological analysis of Nissl-stained sections revealed that the total number of neurons in rabbit AI was 1.48 x 10(6) with a mean neuronal density of 55 x 10(3)/mm3. Based on a mean cortical thickness of 1.92 mm, there are approximately 106,000 neurons in a 1 mm2 column of auditory cortex. PVi yields an extraordinary Golgi-like staining of nonpyramidal cells in all cortical layers. PV+ nonpyramidal cells constitute approximately 7.0% of the neurons in AI. There were significant differences in the morphology and density of PV+ neurons across layers. Although only 5% of cells in lamina I were PV+, three nonpyramidal cell types were present. Lamina II had the highest numerical density within AI but the lowest percentage of PV+ neurons (3.3%). Lamina II, however, contained the greatest diversity of PV+ nonpyramidal cell types, which included small multipolar cells, bipolar cells, and, less frequently, large cells of the bitufted, bipolar, and stellate varieties. Lamina IV had one of the highest numerical densities (67.6 x 10(3) neurons/mm3) and contributed nearly 27% of the total neuron number in AI. The numerical density of PV+ nonpyramidal cells was also greatest within lamina IV (7.1 x 10(3)/mm3) where they formed 10.4% of the neuronal population. PV+ nonpyramidal cells in lamina IV and lamina III were predominantly large basket-type cells with bitufted dendritic domains and tangentially oriented local axonal plexuses. The terminal-like label within lamina III/IV derived in part from the basket-cell axons, which formed pericellular arrays around unstained somata. Cell-sparse lamina V contained the largest PV+ nonpyramidal cells in AI. These cells, which formed 11% of the neuron population in lamina V, were notable for their tangentially oriented dendritic fields and local axonal arbors. PVi partitioned lamina VI into VIa and VIb. Large multipolar nonpyramidal cells were distributed throughout lamina VI and made up approximately 6% of the total population. Lamina VIa contained a band of lightly labeled PV+ pyramidal neurons that formed 15% of the neuronal population.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7860787 TI - Visual and somatosensory inputs to the avian song system via nucleus uvaeformis (Uva) and a comparison with the projections of a similar thalamic nucleus in a nonsongbird, Columba livia. AB - Nucleus uvaeformis (Uva), previously identified as a component of song control circuitry in songbirds, and nucleus dorsolateralis posterior thalami, pars caudalis (DLPc) in pigeon, were compared with respect to their relative positions in the dorsolateral part of the posterior thalamus, their cell types, and their afferent and efferent projections. Both nuclei are closely related to the habenulointerpeduncular tract, have similar cell types, and receive a dense projection from deep layers of the optic tectum, predominantly ipsilaterally, and a distinct projection from the dorsal column and external cuneate nuclei, predominantly contralaterally. Recordings of multiple unit activity evoked by visual and somatosensory stimuli were used to guide injections of tracer into either DLPc or Uva, and the projections to the telencephalon were charted. Both nuclei were found to have a major terminal field in the medial part of the ipsilateral neostriatum intermedium (NI), known as nucleus interfacialis (NIf) in songbirds, and a minor terminal field in the roof of the neostriatum caudale (NC). In pigeon, the DLPc terminations in NC were within a region known as neostriatum dorsale (Nd), and, in male songbirds, the Uva terminations were in the high vocal center (HVC). Recordings of visual and somatosensory evoked activity were then used to guide injections of tracer into NI, and the afferent and efferent projections were again compared in pigeon and songbirds. The projections from either DLPc or Uva were confirmed, and terminal fields were observed either in Nd in pigeon, the dorsolateral part of NC in female songbirds, or HVC in male songbirds. Injections of tracer into either Nd or HVC confirmed their sources of afferents in DLPc or Uva, respectively, and in NI, but there was incomplete overlap of the distribution of retrogradely labelled cells in NI and the terminal fields of DLPc or Uva. It is concluded that DLPc and Uva are comparable nuclei having similar afferent and efferent projections relaying visual and somatosensory information to the telencephalon. The possible role of this information in vocal control is discussed. PMID- 7860788 TI - Architectonic subdivisions of the motor thalamus of owl monkeys: Nissl, acetylcholinesterase, and cytochrome oxidase patterns. AB - As the first part of an investigation of the motor thalamus and its cortical connections in the owl monkey, a New World anthropoid primate, we studied thalamic architecture by using stains for Nissl, acetylcholinesterase (AChE), and cytochrome oxidase (CO), in order to identify subdivisions of the ventrolateral thalamic region as well as other nuclei with motor connections. Material was obtained from brains cut in the frontal, horizontal, and parasagittal planes. Our results indicate that the ventrolateral thalamic region (VL) of owl monkeys is a heterogeneous structure composed of several architectonic subdivisions that resemble divisions that have been described in macaques and other Old World anthropoids. All of these subdivisions are more readily distinguished in AChE than in Nissl or CO preparations. The anterior part of VL, VLa (VLo of Olszewski), is characterized by clusters of medium-sized, darkly stained neurons. VLa is also distinguished by AChE-positive cells embedded in a matrix of neurites as well as by a characteristic dark, irregular net of blood vessels. The posterior part of VL is rather uniform cytoarchitectonically and contains large, darkly stained, and sparsely distributed neurons. However, we were able to distinguish three subdivisions of posterior VL that closely correspond to structures described by Olszewski in macaques: a principal segment, VLp (VPLo of Olszewski), a medial segment, VLx ("area X" of Olszewski), and a dorsal segment, VLd (VLc and VLps of Olszewski). In AChE, VLd is much darker than the other divisions. The distinction between VLp and VLx, which together make up the largest part of VL, is less marked, although VLp is somewhat darker and more irregular in appearance in AChE than is VLx. PMID- 7860789 TI - Colocalization of prosomatostatin-derived peptides in the caudate-putamen of the rat. AB - In the striatum of rat, somatostatin 14, somatostatin 28, and somatostatin 28(1 12) have previously been localized within a small population of medium aspiny local circuit neurons. Because all three peptide fragments are generated through the cleavage of prosomatostatin by different converting enzymes, the possibility for differential expression of these peptides exists. In order to investigate this possibility, frozen sections were collected from the brains of adult female Wistar rats fixed with 4% paraformaldehyde and double labelled using immunocytochemistry and in situ hybridization. Sections were first processed for somatostatin 14, somatostatin 28, or somatostatin 28(1-12) by using the avidin biotin complex immunocytochemical technique followed by in situ hybridization using 35S-labelled antisense riboprobes to somatostatin mRNA. The results of such analysis revealed that somatostatin 28 and somatostatin mRNA are 100% colocalized. Somatostatin 14 and somatostatin 28(1-12), in contrast, are only present within 66% of the neurons that express somatostatin mRNA. Examination of the anatomical distribution of neurons that express both somatostatin mRNA and somatostatin 14 or somatostatin 28(1-12) protein reveals that these neurons are present throughout the caudate-putamen of rat but are more prevalent in the ventromedial regions. Neurons that express somatostatin mRNA but not somatostatin 14 or somatostatin 28(1-12) are also present throughout the caudate-putamen but are most numerous within a dorsolateral strip just beneath the corpus callosum. These results suggest that the somatostatin neuron population within the rat caudate-putamen is actually composed of two smaller subpopulations based on neuropeptide content. The first subpopulation contains somatostatin 28 and constitutes one-third of the total somatostatin population, whereas the other contains somatostatin 28, somatostatin 14, and somatostatin 28(1-12) and represents the remaining two-thirds of the cells that express somatostatin mRNA. PMID- 7860790 TI - Cellular retinol-binding protein type I is prominently and differentially expressed in the sensory epithelium of the rat cochlea and vestibular organs. AB - To understand the possible role of retinoic acid during inner ear development and cellular regeneration, we have examined the expression pattern of two intracellular retinoid-binding proteins, the cellular retinol- and retinoic acid binding proteins of type I in the developing and mature rat inner ear. Expression of cellular retinol-binding protein type I was seen in the supporting cells of the organ of Corti and vestibular organs as soon as the first signs of differentiation of the adjacent hair cells were seen. In the developing organ of Corti, the expression pattern followed the basal-to-apical coil differentiation gradient. After the 1st postnatal week, detectable expression of cellular retinol binding protein type I disappeared from the organ of Corti, but persisted in the supporting cells of vestibular organs throughout life. Expression of cellular retinoic acid-binding protein type I was not found in the inner ear sensory epithelia. Cellular retinol-binding protein type I has previously been shown to act as a substrate carrier in the synthesis of retinoic acid from its precursor, retinol. Our data suggest that retinoic acid is synthesized in the developing sensory epithelium of the cochlear and vestibular organs and that a concentration gradient formed by retinoic acid may have a role in differentiation of the cochlear sensory epithelium. Furthermore, retinoic acid may have a role in damage induced hair cell regeneration in the developing and mature vestibular organs as well as in the developing auditory organ. The absence of cellular retinol-binding protein type I from the supporting cells of the mature organ of Corti may be associated with the inability of this organ to regenerate hair cells after damage. PMID- 7860791 TI - Size-related colocalization of glycine and glutamate immunoreactivity in frog and rat vestibular afferents. AB - Presence and distribution of glutamate, glycine, GABA and beta-alanine in VIIIth nerves of frogs and rats were investigated with postembedding immunocytochemical methods on serial semithin sections. In Scarpa's ganglion of the frog, all cell bodies were glutamate immunoreactive. About 17% of the cells per section were also glycine immunoreactive, but none were GABA or beta-alanine immunoreactive. The mean diameter of glycine-positive cell bodies (26.7 +/- 6.9 microns; N = 130) was significantly (P < 0.0001) larger than that of glycine-negative cell bodies (15.7 +/- 5.4 microns; N = 272). The intensity of glutamate immunostaining decreased with cell diameter, whereas the intensity of glycine immunostaining increased with cell diameter. As a result, the staining intensities for glutamate and glycine in a given cell were negatively correlated. Glycine immunoreactivity was also present in a size-related manner in distal and proximal afferent fibers. The majority of thin fibers (< 4 microns) was glycine negative, whereas most of the thick fibers (> 10 microns) were glycine positive. Glycine-positive fibers were observed in the sensory epithelial of all end organs in the inner ear. The saccular macula and its nerve, however, contained only few glycine immunoreactive structures. In Scarpa's ganglion of the rat, all cells were immunoreactive for glutamate, about 12% for colocalized glycine, and none for GABA or beta-alanine. Glycine-positive cell bodies were significantly (P < 0.0001) larger (32.2 +/- 5.2 microns; N = 82) than glycine-negative cell bodies (25.1 +/- 5.3 microns; N = 274). Cell bodies in the spiral ganglion were only glutamate immunoreactive, whereas staining for glutamate, glycine, and GABA was dense in the ventral cochlear nucleus. These results demonstrate that thicker vestibular afferent fibers represent a particular subpopulation that differs from the majority of thinner afferents due to their glycine immunoreactivity. PMID- 7860792 TI - Metabotropic glutamate receptor mGluR1 distribution and ultrastructural localization in hypothalamus. AB - The metabotropic glutamate receptor mGluR1 is a G-protein-coupled glutamate receptor whose activation induces phosphotidylinositol hydrolysis and increases diacylglycerol and cytoplasmic calcium. By using affinity-purified antisera against a partial amino acid sequence of mGluR1 alpha, deduced from the nucleotide sequence of the cloned gene, the heterogeneous expression of this glutamate receptor was studied immunocytochemically with light and electron microscopy in the rat hypothalamus. Immunoreactivity was restricted to cell bodies and dendrites throughout many regions of the adult hypothalamus, including the preoptic area, anterior hypothalamus, suprachiasmatic nucleus, dorsomedial hypothalamus, and periventricular region. Strong immunolabeling was found in the lateral hypothalamus where immunoreactivity could be detected as early as embryonic day 18. Intense immunoreactivity was also found in the medial mammillary nuclei. In contrast to the strong labeling in many other regions, the neuroendocrine neurons of the arcuate, supraoptic, and paraventricular nuclei showed relatively little staining in adults. With light microscopy, immunoperoxidase labeling was found distributed in patches on the cytoplasmic side of the plasma membrane of immunoreactive neurons. When the same tissue was examined ultrastructurally, the patches were not restricted to synaptic specializations but were also found distributed on perikaryal and dendritic membranes sometimes associated with synapses and sometimes not. Some immunoreactive membranes showed no immunolabeling at the synaptic junction. When the tissue was strongly stained, labeling could be found in the cytoplasm of immunoreactive cells. No immunostaining was found on axons or presynaptic boutons. Together with other evidence showing a widespread expression of many different subtypes of both ionotropic and metabotropic receptors, these data support the hypothesis that glutamate may regulate hypothalamic cellular activity with a number of physiologically different mechanisms, and these mechanisms include second-messenger systems activated by G proteins. PMID- 7860793 TI - Neuroarchitecture of the tritocerebrum of Drosophila melanogaster. AB - The organisation of the tritocerebrum of Drosophila melanogaster was studied by Bodian-Protargol reduced silver staining, Golgi-silver impregnation, horseradish peroxidase (HRP), and cobalt-chloride labelling of neurones and transmission electron microscopy. Nerve fibres of six categories were found to project to the tritocerebrum. (1 and 2) The sensory fibres from the internal mouthpart sensilla known to course along pharyngeal and accessory pharyngeal nerves were found to project in mainly two tiers, in the tritocerebrum. (3) Stomodaeal nerve fibres also project along the pharyngeal nerve, to the tritocerebrum. (4) Cells of the pars intercerebralis (PI) project along the median bundle and arborise in the tritocerebrum. HRP labelling and subsequent examination by transmission electron microscopy indicated their neurosecretory nature. (5 and 6) Two tracts of ascending fibres, designated as dorsal and ventral ascending tracts, were found to project to the tritocerebrum. Some of the sensory fibres from the labial nerve extend close to the sensory projections of the tritocerebrum, suggesting a possible convergence of the two sensory inputs. In the tritocerebrum, the sensory input, the stomodaeal input, the neurosecretory fibres of PI, and the ascending fibres were found to have overlapping fields, suggesting mutual interaction. The medial subesophageal ganglion and the tritocerebrum may interact through the ventral ascending tract. PMID- 7860795 TI - Early development of the optic chiasm in the gray short-tailed opossum, Monodelphis domestica. AB - We have studied the early development of the uncrossed retinofugal projection in the gray short-tailed opossum. Axons that form the adult uncrossed retinofugal projection arise from the temporal crescent of the retina and reach the optic chiasm on postnatal day 7. The sites at which the uncrossed fibres segregate from the crossed fibres and the pattern of this segregation are very different from those seen in eutherian mammals. In the opossum, the uncrossed fibres segregate from the crossed fibres within the juxtachiasmatic part of the optic nerve before they have encountered either the fibres of the other eye or midline structures of the ventral diencephalon. The uncrossed fibres turn perpendicular to the axis of the nerve and grow dorsoventrally through the crossed projection to gather as a discrete bundle at the ventral edge of the nerve. The abrupt divergence of the uncrossed fibres occurs at a border between two glial cell types: the interfascicular glia that characterise the main part of the optic nerve and the radial glia of the juxtachiasmatic part of the nerve. At the ventral part of the nerve, the bundle of uncrossed fibres turns caudally across the axis of the nerve and enters the ipsilateral optic tract. When retinofugal fibres encounter the border between the interfascicular and radial glia, a very specific axonal reorganisation occurs in marsupials, and this is strikingly different from the axonal reorganisation that occurs at the same site in eutherians, where essentially all retinofugal fibres reorganise, not just the uncrossed component. We believe this to be an important example of an identified cellular element that has quite distinct axon-guidance properties in different species. PMID- 7860794 TI - Uniglomerular projection neurons participate in early development of olfactory glomeruli in the moth Manduca sexta. AB - Glomerular organization of the antennal (olfactory) lobe is initiated by the arrival of sensory axons from the antenna. Bundles of axon terminals coalesce into spheroidal knots of neuropil called protoglomeruli. Previous studies have suggested that the protoglomeruli form a template for the mature glomerular array, but an early role for projection neurons in establishing the template has not been excluded. We examined with the confocal laser scanning microscope the morphological development of the uniglomerular projection neurons during the stages in which glomeruli are constructed. Groups of projection neurons were stained with the lipophilic dye DiI to assess the development of the population as a whole; individual neurons were filled intracellularly with Lucifer Yellow to examine in detail the development of shape. In some preparations, sensory axons and glial cells also were labeled by using different fluorescent dyes to reveal possible interactions between projection neuron dendrites and sensory axons or glial cells. Protoglomeruli form in a wave beginning at the entry point of the antennal nerve and proceeding across the lobe to the opposite pole. A second wave follows in which projection neurons become tufted and innervate the newly formed glomeruli, sometimes extending into the glial border surrounding the protoglomeruli. In animals deprived of sensory axons, some projection neurons still form tufted dendritic trees and, in one region of the neuropil, a glomerulus-like structure. The early presence of projection neuron processes in the protoglomeruli and the formation of at least one glomerulus-like structure in unafferented lobes suggest that uniglomerular projection neurons play an active role in the construction of olfactory glomeruli. PMID- 7860796 TI - Ipsi- and contralateral commissural growth cones react differently to the cellular environment of the ventral zebrafish spinal cord. AB - Early commissural axons in the zebrafish spinal cord extend along a pathway consisting of a ventrally directed ipsilateral, a contralateral diagonal, and a contralateral longitudinal segment. The midline floor plate cell is one important cue at the transition from the ipsilateral to the contralateral pathway segments. In order to identify additional guidance cues, the interactions between commissural growth cones and their substrates were examined at the electron microscopic level in the different pathway segments. The growth cones extended near the superficial margin of the spinal cord, within filopodial reach of three bilateral longitudinal axon pathways that were ignored irrespective of whether other axons were already present. Ultimately the commissural growth cones pioneered an additional independent longitudinal pathway in the dorsolateral spinal cord. Neuroepithelial cells were extensively contacted in the lateral marginal zone of the dorsal spinal cord and are thus in a position to contribute to the establishment of the longitudinal commissural pathway segment. The extent of contact with neuroepithelial cells in the ventral spinal cord was dependent on whether commissural growth cones had already crossed the ventral midline: ipsilateral, but not contralateral, growth cones showed extensive contacts with neuroepithelial processes and minor contacts with the basal lamina. In marked contrast, commissural growth cones that had already crossed the ventral midline and entered the diagonal pathway segment showed major appositions to the basal lamina. Extensive contact with the basal lamina was first established in the ventral midline region, where crossing growth cones always inserted between the basal lamina and the base of the midline floor plate cells. This indicates that a change occurs in the response characteristics of commissural growth cones as they cross the ventral midline of the spinal cord. Such a change could help to explain why the growth cones extend first toward but then away from the ventral midline. PMID- 7860797 TI - GABAA receptor alpha 1 subunit, an early marker for area specification in developing rat cerebral cortex. AB - Changes in the expression of neurotransmitter receptors in developing cerebral cortex may be related to the functional maturation of distinct areas. In the present study, we have tested whether GABAA receptor expression in neonatal rats reflects the differentiation of cortical areas. Specifically, the alpha 1 subunit, one of the most prevalent GABAA receptor subunits in adult cerebral cortex, is up-regulated postnatally, suggesting a link with the establishment of inhibitory circuits. Using immunohistochemistry with a subunit-specific antiserum, we observed a striking area- and lamina-specific increase in staining for GABAA receptors containing the alpha 1 subunit (alpha 1-GABAA receptors), from low levels in neonates to an intense and uniform staining in adults. Already at birth, the alpha 1-subunit immunoreactivity selectively demarcated the boundaries of certain cortical areas. In particular, the primary somatosensory (S1) and visual (V1) areas were distinctly delineated with a band of alpha 1 subunit immunoreactivity located in the developing layers III and IV. The staining ended abruptly at the presumptive boundaries of S1 and V1, adjacent areas being unstained at this age. Around postnatal day 3, clusters of alpha 1 subunit positive cells were seen in layers III-IV of S1 and V1 extending their dendrites up to layer I, where they arborized profusely. In addition, the distribution of alpha 1-GABAA receptors in S1 revealed in detail the differentiation of the barrel field during early postnatal development. Although staining was observed in all areas by postnatal day 6, differences in the laminar distribution of alpha 1-GABAA receptors persisted for at least 1 more week. Our results provide evidence for the existence of area-specific boundaries in neocortex of newborn rats before layers III-IV are fully differentiated and innervated by cortical afferents. Furthermore, the area- and lamina-specific maturation of alpha 1-GABAA receptor staining demonstrates the value of this marker for investigating the cytoarchitectonic differentiation of cortical areas during development. PMID- 7860798 TI - Replacement of an inherited stretch receptor by a newly evolved stretch receptor in hippid sand crabs. AB - Primary sensory neurons that are motoneuron-like in morphology and often nonspiking (transmit afferent signals as graded depolarizations) characterize an unusual type of stretch receptor in decapod crustaceans. Nonspiking and spiking receptors occur in similar positions at homologous joints in different species and have been presumed to be homologous, the spiking one considered "primitive". To better understand the evolutionary origin of these stretch receptors and why some are nonspiking, we examined the spiking telson-uropod stretch receptors in the spiny sand crab Blepharipoda occidentalis (Albuneidae) and the squat lobster Munida quadrispina (Galatheidae) and compared them with the nonspking telson uropod stretch receptor of the mole sand crab Emerita analoga (Hippidae). The position, morphology and responses to stretch of the sensory neurons, and the ultrastructure of the elastic strand portion of the receptor are similar in M. quadrispina and B. occidentalis, except that in B. occidentalis the receptor muscles are substantially smaller and the extracellular matrix of the elastic receptor strand is both more extensive and more organized, reminiscent of the ultrastructure of E. analoga's nonspiking receptor. We conclude that the spiking telson-uropod stretch receptors of albuneids and galatheids are homologous. The differences in the ultrastructure of their receptor strands imply that the efficiency of coupling receptor length change to deformation of the dendritic termini increases in the order M. quadrispina < B. occidentalis < E. analoga. The spiking and nonspiking telson-uropod stretch receptors differ anatomically in three major respects that appear to preclude their homology. (1) The receptor strands are on opposite sides of a conserved muscle. (2) The sensory somata are in different regions of the sixth abdominal ganglion: a lateral cluster of somata for the spiking sensory neurons and two medial clusters, one anterior, one posterior, for the nonspiking sensory neurons. (3) The neuropil projections of the sensory neurons are different. We conclude that the hippid's nonspiking telson-uropod stretch receptor evolved de novo and not by modification of the ancestral anomuran telson-uropod stretch receptor (which Hippidae have lost). PMID- 7860799 TI - Distribution of messenger RNAs encoding enkephalin, substance P, somatostatin, galanin, vasoactive intestinal polypeptide, neuropeptide Y, and calcitonin gene related peptide in the midbrain periaqueductal grey in the rat. AB - The midbrain periaqueductal grey matter (PAG) has numerous functional roles that include mediating nociceptive inhibition and integrating behavioural and physiological responses to potentially threatening or stressful stimuli. Underlying these behaviours is the diverse interconnectivity of this region, and it is possible that neurochemical subdivisions within the PAG reflect the functional properties of the different PAG regions. In this study, using in situ hybridization, we have investigated the distribution in the rat PAG of the messenger ribonucleic acids (mRNAs) encoding seven neuropeptides: enkephalin (ENK), substance P (SP), somatostatin (SST), galanin (GAL), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP). Each peptide mRNA had a distinct topographical distribution in the PAG. Preproenkephalin A (ENK) mRNA-expressing cells were found at all levels of the PAG in three distinct longitudinal columns. Preprotachykinin A (SP)-expressing cells were found at all levels of the PAG, principally in the Edinger-Westphal nucleus and the lateral and dorsal PAG. There was a column of neurons producing mRNA-encoding somatostatin that extended along the rostrocaudal extent of the ventrolateral PAG; there were also labelled cells in the dorsal and dorsolateral subdivisions at some levels of the PAG. Galanin mRNA-producing neurones were limited to the dorsal raphe nucleus and to a second population in the ventral border of the aqueduct. VIP mRNA-producing neurones were found in very localized regions of the PAG, including the cell-sparse region immediately ventral to the aqueduct and the ventral part of the dorsal raphe nucleus. NPY mRNA-producing neurones were localized mainly in some cells of the Edinger-Westphal nucleus and dorsal raphe nucleus. CGRP mRNA-expressing neurons were limited to the oculomotor and trochlear nucleus. The results showed a topographical distribution of neuropeptides over the rostrocaudal extent of the PAG that is compatible with the emerging theory that the anatomical and functional specificity of the PAG is expressed in the form of longitudinally arranged neuronal columns that extend for varying distances along the rostrocaudal axis of the midbrain PAG. PMID- 7860800 TI - Development of catecholamine systems in the brain of the lizard Gallotia galloti. AB - For a better insight into general and derived traits of developmental aspects of catecholaminergic (CA) systems in amniotes, we have studied the development of these systems in the brain of a lizard, Gallotia galloti, with tyrosine hydroxylase (TH)- and dopamine (DA) immunohistochemical techniques. Two main groups of TH-immunoreactive (THi) perikarya appear very early in development: one group in the midbrain which gives rise to the future ventral tegmental area, substantia nigra and retrorubral cell groups, and another group in the tuberomammillary hypothalamus. Somewhat later in development, TH/DA immunoreactive cells are observed in the thalamus, rostrodorsal hypothalamus and spinal cord, and, with another delay, in the suprachiasmatic nucleus, the periventricular organ, and the pretectal posterodorsal nucleus. CA cell groups that appear rather late in development include the cells in the olfactory bulb, the locus coeruleus and the caudal brainstem. As expected, the development of immunoreactive fibers stays behind that of the cell bodies, but reaches the adult like pattern just prior to hatching. The present study revealed considerable variation in the relation between the state of cytodifferentiation and first expression of TH/DA immunoreactivity between CA cell groups. Catecholamine cells in the midbrain and tuberomammillary hypothalamus are still migrating, immature (absence of dendrites) and express only TH immunoreactivity at the time of first detection. Cells which appear at later developmental stages lie already further away from the ventricle, possess two or more dendritic processes, and generally express both TH- and DA immunoreactivity. PMID- 7860801 TI - Timecourse of development of the wallaby trigeminal pathway. I. Periphery to brainstem. AB - The development of the vibrissae and their innervation and the maturation of the brainstem trigeminal sensory nuclei have been studied in the wallaby, Macropus eugenii, from birth to adulthood. At birth, developing vibrissal follicles consist of solid epidermal pegs surrounded by dermal condensations. The developing follicles and adjacent skin are innervated by trigeminal afferents. Ten days after birth the follicle contains a dermal papilla and the deep vibrissal nerve can be recognised. A hair cone is present at postnatal day (P) 30 and hairs are apparent on the skin surface by P35. By P63 the deep vibrissal nerve can be seen innervating Merkel cells in the outer root sheath; in addition, the first signs of the blood sinus can be recognised. Innervation of the inner conical body and lanceolate and lamellated receptors supplying the mesenchymal sheath and waist region are not seen until P119, when the follicle resembles that seen in the adult. At birth, central processes of the trigeminal ganglion cells have entered the trigeminal tract and extend from the rostral pons to the upper cervical cord. Labelling with a carbocyanine dye at P0 shows afferents extending medially from the tract into the trigeminal subnuclei at all levels. At this stage the trigeminal nuclei appear as areas of increased cell density in the lateral brainstem. By P30-40 the four subnuclei can be distinguished on the basis of shape, cytoarchitecture, and succinic dehydrogenase reactivity. Adult morphology is not fully established until P210. In mature animals, nucleus principalis contains closely packed, polymorphic cells, frequently aligned parallel to thick fibre bundles that traverse the nucleus obliquely. Subnuclei oralis and interpolaris contain sparsely distributed, medium to large cells, randomly oriented, as well as prominent rostrocaudally directed fibre bundles. Subnucleus caudalis consists of the marginal layer, substantia gelatinosa, and magnocellular layers as described in other species. Patches of increased succinic dehydrogenase or cytochrome oxidase reactivity, presumably corresponding to the vibrissae, are present in subnuclei principalis, interpolaris, and caudalis in developing and adult animals, although the pattern is less clear than in rats. The brainstem patches are first seen at P40, approximately 6 weeks before the corresponding vibrissal-related pattern develops in the cortex. This suggests that the onset of patch formation may be regulated independently at different levels of the pathway. PMID- 7860802 TI - Vitread proliferation of filamentous processes in avian Muller cells and its putative functional correlates. AB - In order to examine to what extent the neuronal and metabolic activities of avascular vertebrate retinae are reflected in the morphology of their Muller cells we have studied (by using several monoclonal antibodies) the morphology of Muller cells in two species of diurnal birds (chicken, Gallus domesticus, and pigeon, Columba livia) and one species of nocturnal saltwater crocodiles (Crocodylus porosi). In all three species, the outer nuclear layer is relatively thin and the Muller cell trunks divide into rootlets that wrap around the photoreceptors. In both diurnal birds studied, the trunks of Muller cells in the inner plexiform layers invariably divide into numerous fine filamentous processes that terminate in small expansions covering most of the vitreal surface of the retina. Furthermore, the networks of filamentous processes of birds' Muller cells exhibit conspicuous horizontal lamination in the inner plexiform layer. In contrast, the filamentous processes arising from the individual Muller cell trunks of the crocodile, if present, are much less numerous and less widely spread than those of diurnal birds. It is proposed that the splitting of the Muller cell trunks into numerous filamentous processes terminating in small vitreal expansions represents a morphological adaptation for: 1) effective spatial buffering of K+ ions in thick and presumably metabolically highly active, yet avascular, avian retinae, and 2) effective absorption and distribution of nutrients leaking from the vitreally located supplemental nutritive organ, the pecten. PMID- 7860803 TI - Oxygen consumption rates of adults and chicks during brooding in king quail (Coturnix chinensis). AB - Oxygen consumption rates were measured in chicks (0-17 days of age), and in non brooding and brooding adults. Brooded chicks maintained a constant oxygen consumption rate at a chamber ambient temperature of 10-35 degrees C (0-5 days of age: 2.95 ml O2.g-1.h-1 and 6-17 days of age: 5.80 ml O2.g-1.h-1) while unbrooded chicks increased oxygen consumption rate at ambient temperature below 30 degrees C to double the brooded oxygen consumption rate at 25 and 15 degrees C for chicks < 5 days of age and > 5 days of age, respectively. The mass-specific oxygen consumption rate of breeding male and females (non-brooding) were significantly elevated within the thermoneutral zone thermal neutral zone (28-35 degrees C) in comparison to non-breeding adults. Below the thermal neutral zone, oxygen consumption rate was not significantly different. The elevation in oxygen consumption rate of breeding quail was not correlated with the presence of broodpatches, which developed only in females, but is a seasonal adjustment in metabolism. Male and females that actively brooded one to five chicks had significantly higher oxygen consumption rate than nonbrooding quil at ambient temperature below 30 degrees C. Brooding oxygen consumption rate was constant during day and night, indicating a temporary suppression of the circadian rhythm of metabolism. Brooding oxygen consumption rate increased significantly with brood number, but neither adult body mass nor adult sex were significant factors in the relationship between brooding oxygen consumption rate and ambient temperature. The proportion of daylight hours that chicks were brooded by parents was negatively correlated with ambient temperature. After chicks were 5 days old brooding time was reduced but brooding oxygen consumption rate was unchanged. Heat from the brooding parent appeared to originate mainly from the apteria under the wings and legs rather than the broodpatch. The parental heat contribution to chick temperature regulation below the chicks' thermal neutral zone is achieved by increasing parental thermal conductance by a feedback control similar to that suggested for the control of egg temperature via the broodpatch. It is concluded that the brooding period is an energetic burden to parent quail, and the magnitude of the cost increases directly with brood number and inversely with ambient temperature during this period.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7860804 TI - Endogenous cholecystokinin is not a major regulator of food intake in the chicken. AB - This study investigated whether or not endogenous cholecystokinin exerts satiety effects in chickens. After several doses (0, 1, 2 and 4 micrograms.kg body weight 1) of intravenous injection of caerulein, the bile flow was increased in a dose dependent fashion. However, the pharmacological level of caerulein failed to suppress the food intake of chickens. Two potent stimulators of endogenous cholecystokinin, i.e., soybean trypsin inhibitor and phenylalanine were administered to chickens before feeding and food intake was determined over 2 h. The soybean trypsin inhibitor and phenylalanine did not alter food intake. Devazepide, a cholecystokinin-A receptor antagonist, significantly decreased amylase release from the dispersed chicken pancreatic acini stimulated by caerulein. However, devazepide did not improve food intake of the chicken. The results obtained suggest that endogenous cholecystokinin may not act as a satiety signal in chickens. PMID- 7860805 TI - Cold-induced changes in brown adipose tissue thermogenic capacity of immunocompetent and immunodeficient hairless mice. AB - Mild cold acclimation (22 degrees C, 3 weeks) of hairless mice was shown to increase 5-fold the brown adipose tissue uncoupling protein content in immunodeficient BALB/c nu/nu mice, but by only 2.3-fold in immunocompetent BFU mice. The difference in activation of brown adipose tissue thermogenic capacity was due to a 2-fold increase in the content of brown adipose tissue in nu/nu mice only, which was paralleled by an increase in brown adipose tissue protein but not DNA content. Likewise, only in nu/nu mice the cold acclimation increased the reaction of natural killer cells in blood and peritoneal exudate with a shift from spleen to lymph nodes and increased the phagocytic index. The results indicate that the immune system may influence the defence against cold at the level of brown adipose tissue thermogenesis. PMID- 7860806 TI - Effects of dehydration on organ metabolism in the frog Pseudacris crucifer: hyperglycemic responses to dehydration mimic freezing-induced cryoprotectant production. AB - The metabolic effects of evaporative water loss at 5 degrees C were assessed for both fall- and spring-collected spring peepers Pseudacris crucifer. Frogs readily endured the loss of 50% of total body water. During dehydration organ water content was defined with no change in water content in skeletal muscle, gut, and kidney of 50% dehydrated frogs and reduced water content in liver, brain and heart. Dehydration stimulated a rapid and massive increase in liver glucose production. In fall-collected frogs liver glucose rose by 120-fold to 2690 +/- 400 nmol.mg protein-1 or 220 mumol.g ww-1 in 50% dehydrated frogs and glucose in other organs increased by 2.6- to 60-fold. Spring-collected frogs showed the same qualitative response to dehydration although absolute glucose levels were lower, rising maximally by 8.4-fold in liver. Glucose synthesis was supported by glycogenolysis in liver and changes in the levels of glycolytic intermediates in liver indicated that an inhibitory block at the phosphofructokinase locus during desiccation helped to divert hexose phosphates into the production of glucose. Liver energy status (ATP, total adenylates, energy charge) was maintained even after the loss of 35% of total body water but at 50% dehydration all parameters showed a sharp decline; for example, energy charge fell from about 0.85 to 0.42. Severe dehydration also led to an accumulation of lactate in four organs, probably hypoxia-induced due to impaired circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7860807 TI - Introduction to the special section: research on the nature and treatment of alcoholism--does one inform the other? AB - Although the 2 topics of the nature and treatment of alcoholism have both been investigated for years, they are just recently beginning to interface with and complement one another. This special section addresses the interface from both perspectives and covers content areas that touch on current issues, research and treatment trends, and controversies in the alcohol field. The first 2 articles focus on the nature of alcoholism with commentary on implications for treatment, and the second 4 articles shift to examine research on treatment of alcohol problems, with implications for understanding the nature of alcoholism. This introductory article describes the special section, summarizes the articles in the section and integrates the information to discuss areas of increasing interface between research on the nature and treatment of heterogeneous substance abuse problems. PMID- 7860808 TI - Alcoholism: a developmental disorder. AB - Alcoholism etiology is discussed from a developmental behavior genetic perspective. At the outset point, temperament characteristics, by means of ongoing and reciprocal interaction with the social environment, shape the course of behavioral development. The behavioral characteristics successively acquired during development are vectors that determine the ontogenetic trajectory that culminates ultimately in the clinical disorder of alcoholism. The temperament features that appear to be associated with a heightened risk for alcoholism are examined. Their interactions with the environment during the course of development are considered within an epigenetic framework and, as discussed, have important ramification for improving the prevention and treatment of alcoholism. PMID- 7860809 TI - A developmental-genetic model of alcoholism: implications for genetic research. AB - The research for biological-genetic markers of alcoholism is discussed in the context of a multifactorial, heterogeneous, developmental model of the disease. It is suggested that the strategies used in both linkage and association studies require modification to accommodate this more complex model. It is also suggested that several extant associations of genetic markers with alcoholism represent true secondary interactive phenomena that alter the outcome of primary alcoholism genotypes at the phenotype level. PMID- 7860810 TI - Implications of recent neuropsychopharmacologic research for understanding the etiology and development of alcoholism. AB - Recent studies in animals and humans have begun to provide insight into the neuropsychopharmacologic basis of alcohol consumption and dependence. Studies involving the serotonergic and opioidergic neurotransmitter systems have shown the most consistent results. Concurrent nosologic developments have led to the identification of subtypes of alcoholism on the basis of their clinical features and patterns of inheritance of alcoholism. These subtypes, which have implications for both the etiology and development of alcoholism, have also been linked theoretically to specific neurotransmitter systems. Consequently, the typologies both provide a hypothetical basis for selecting specific pharmacotherapies and have implications for molecular genetic investigation. This article selectively reviews the literature in these various areas in an effort to enhance understanding of the etiology and development of alcoholism. PMID- 7860811 TI - Avoiding the horrid and beastly sin of drunkenness: does dissuasion make a difference? AB - Nearly 3 centuries ago, an anonymous English author prepared an educational brochure to dissuade problem drinkers from the "horrid and beastly sin of drunkenness" (Anonymous, 1705). During the past 2 decades, more than 25 randomized trials have been conducted in 12 countries to evaluate 2 basic questions: (a) Does dissuasion make a difference, and (b) What kinds of dissuasion work best? In response to the first question, studies indicate that dissuasion does make a difference with heavy drinkers who have not developed severe alcohol dependence. In response to the second question, the evidence is more equivocal because of the practical and methodological problems encountered in the comparison of different interventions. It is concluded that changes sometimes attributed to specific behavioral and psychological interventions may be due to a combination of advice, individual motivation, and nonspecific social influence. PMID- 7860812 TI - Similarity of outcome predictors across opiate, cocaine, and alcohol treatments: role of treatment services. AB - This study examined the patient and treatment factors associated with 6-month outcome in 649 opiate-, alcohol-, and cocaine-dependent (male and female) adults, treated in inpatient and outpatient settings, in 22 publicly and privately funded programs. Outcomes were predicted by similar factors, regardless of the drug problem of the patient or the type of treatment setting or funding. Greater substance use at follow-up was predicted only by greater severity of alcohol and drug use at treatment admission, not by the number of services received during treatment. Better social adjustment at follow-up was negatively predicted by more severe psychiatric, employment, and family problems at admission and positively predicted by more psychiatric, family, employment, and medical services provided during treatment. PMID- 7860813 TI - Alcoholics Anonymous and behavior therapy: can habits be treated as diseases? Can diseases be treated as habits? AB - Alcoholics Anonymous (AA) and behavior therapy have often been characterized as having opposing views of the nature and treatment of alcohol problems. This article describes the theoretical foundations, view of the change process, and treatment practices of AA and behavior therapy. Theoretical and practice perspectives on integration of the two models are examined, and advantages and disadvantages of integration are discussed. PMID- 7860814 TI - Recall of childhood trauma: a prospective study of women's memories of child sexual abuse. AB - One hundred twenty-nine women with previously documented histories of sexual victimization in childhood were interviewed and asked detailed questions about their abuse histories to answer the question "Do people actually forget traumatic events such as child sexual abuse, and if so, how common is such forgetting?" A large proportion of the women (38%) did not recall the abuse that had been reported 17 years earlier. Women who were younger at the time of the abuse and those who were molested by someone they knew were more likely to have no recall of the abuse. The implications for research and practice are discussed. Long periods with no memory of abuse should not be regarded as evidence that the abuse did not occur. PMID- 7860815 TI - Forgetting sexual trauma: what does it mean when 38% forget? AB - L. M. Williams (1994) has shown that many women who were sexually abused as children do not report the abuse when questioned 2 decades later. These findings do not support certain freely made claims about memory, but they do support other claims. The findings do not provide cogent support for the claim that a long stream of childhood sexual traumas is routinely banished from conscious awareness and then can be reliably recovered later. The findings do support the claim that many children can forget about a sexually abusive experience from their past. Extreme claims such as "if you were raped, you'd remember" are disproven by these findings. PMID- 7860816 TI - Head injury in partner-abusive men. AB - Research into etiology of marital aggression has focused primarily on psychosocial, political, and cultural factors, to the exclusion of physiological influences. Fifty-three partner abusive men, 45 maritally satisfied, and 32 maritally discordant, nonviolent men were evaluated for past history of head injury, by a physician who was not informed of group membership and aggression history. Logistic regressions confirmed that head injury was a significant predictor of being a battered. The implications of these findings for both marital aggression and post-head injury rehabilitation are discussed. PMID- 7860817 TI - Relationships between adjustment to HIV and both social support and coping. AB - This study examined the relationships between HIV stage, social support, coping strategies, and adjustment to HIV. Ninety-six HIV-infected gay men and 33 seronegative comparison group participants participated in the study. In general, coping strategies and social support did not differ according to HIV stage. As predicted, adjustment was related to social support and coping strategies. Coping strategies were linked to psychosocial adjustment, whereas social support was more strongly associated with health-related variables. There was little evidence of buffering effects of either coping strategies or social support. Four coping strategies were related to low levels of psychological distress. Contrary to expectation, the relationships between coping strategies and adjustment did not vary as a function of HIV stage. However, the relationship between adjustment and some elements of social support varied as a function of HIV stage. PMID- 7860818 TI - Behavioral self-regulation in adolescents with type I diabetes: negative affectivity and blood glucose symptom perception. AB - The hypothesis that negative affectivity (NA) is associated with accuracy of blood glucose (BG) symptom perceptions and diabetes control was assessed. After completing measures of BG symptom beliefs and NA-related constructs (i.e., attentional focus and trait anxiety), 35 adolescents with insulin-dependent diabetes monitored their physical symptoms and their actual BG levels 3 times daily for 2 weeks. Each subject's actual BG symptoms were determined by correlating symptom ratings with BG levels and were then compared with symptom beliefs. Those who were more internally focused were more able to discern which symptoms actually covaried with BG fluctuations; those with higher trait anxiety tended to misattribute non-diabetes-related symptoms to BG levels. Finally, interactions suggested that those who both attend to internal physical sensations and experience-heightened anxiety display poorer metabolic control. PMID- 7860819 TI - Somatic complaints in pediatric patients: a prospective study of the role of negative life events, child social and academic competence, and parental somatic symptoms. AB - This prospective study of 197 pediatric patients with chronic abdominal pain examined the role of negative family life events and several potential moderator variables (child social and academic competence, parental somatic symptoms, and child sex) in child somatic complaints 1 year after a clinic visit. Results indicated that (a) among children low in social competence at the time of the initial clinic visit, higher levels of subsequent negative life events predicted higher levels of somatic complaints at follow-up; (b) among boys in families with high levels of negative life events, those whose mothers were characterized by high levels of somatic symptoms had higher levels of somatic complaints at follow up; and (c) children whose fathers were characterized by high levels of somatic symptoms showed higher levels of somatic complaints at follow-up, regardless of the level of life events. Possible mechanisms accounting for these findings are discussed. PMID- 7860820 TI - Visual stimulation facilitates penile responses to vibration in men with and without erectile disorder. AB - This study compared reflexogenic and psychogenic penile responses in men with and without erectile disorder. It was hypothesized that men with psychogenic erectile dysfunction respond minimally to vibrotactile stimulation. An enhancement of penile responses was expected when vibration was combined with erotic film. Patients were 50 men with psychogenic erectile dysfunction, 45 men with organic erectile dysfunction, and 50 sexually functional men. The combination of film and vibration resulted in stronger penile responses than the stimuli presented separately. Men with psychogenic erectile dysfunction and sexually functional men did not differ in responses to film and film-and-vibration conditions. As predicted, responses of the 2 groups were different in the vibration condition. Interpretations are provided in terms of attention and appraisal. The findings are relevant to the development of psychophysiological diagnostic procedures. PMID- 7860821 TI - Relation between depressive symptoms and stressful life events in a sample of disadvantaged mothers. AB - The bidirectional relation between life events and self-reported depression was examined across a 1-year period. With Time 1 depression controlled, Time 2 stress accounted for an additional 10% of Time 2 depressive symptoms. Health-related stress, family violence, and financial stress at Time 2 predicted Time 2 depression after control for Time 1 depression. With Time 1 stress controlled, Time 2 depression accounted for 8% of the variance in Time 2 stress. Time 2 depression predicted Time 2 health-related stress, financial stress, household changes, spouse-partner stress, family violence stress, and substance abuse stress, controlling for each of these stressors at Time 1. The results describe a complex relation between stress and depression and suggest that the relation between stress and depression is moderated by the type of stress. PMID- 7860822 TI - Posttraumatic stress disorder and war-zone exposure as correlates of perceived health in female Vietnam War veterans. AB - Previous studies have identified traumatic exposure and posttraumatic stress disorder (PTSD) as predictors of physical health complaints without considering the relationship between exposure and PTSD. This study examined the unique associations of war-zone exposure and PTSD with perceived physical health outcomes in a nontreatment-seeking sample of 109 female veterans of the Vietnam War who responded to a series of psychological, exposure, and health questionnaires. Both PTSD and exposure were associated with reports of negative health outcomes when each variable was not adjusted for the other. The effects associated with exposure decreased when PTSD was controlled for, whereas the effects associated with PTSD remained when exposure was controlled for. Results suggest that effects of traumatic exposure on perceived health are partially mediated by increases in PTSD after exposure, supporting studies on the effects of stress on health. PMID- 7860823 TI - Detection performance of the ideal decision function and its McLaurin expansion: signal position unknown. AB - Although optimal decision functions for many simple detection/discrimination tasks can be cast in a form linear in the signal data, more complicated tasks require the addition of higher-order terms. This is typically the case when parameter uncertainty is allowed, in imaging for example, for the detection of a target of known size and shape but unknown position in a noise field. The simple task of detecting signals known exactly except for position, specifically detection of a "boxcar" shaped signal on a uniform data trace, has been studied in order to elucidate the relative importance of the first-, second-, or higher order terms of the likelihood ratio decision rule. Analytical expressions have been developed to describe signal-to-noise ratios relevant for performance evaluation at low signal contrast levels, and computer simulations have been used to evaluate performance at higher contrast. It was found that for this task the first-order term (which corresponds to measuring the mean value of the data) dominates for low contrast signals but is superseded by higher-order terms (which is jth order correspond to the jth-order correlation of the data match filtered with the jth-order correlation of the signal) as contrast is increased. The quadratic term is found to be inferior to the linear term for small contrast and to the cubic for all values of signal contrast if the background is held constant. When the background level is allowed to vary, the performance of the odd-order terms decreases relative to that of the quadratic (and other even-order ones). Various measures of decision function efficiency are compared, demonstrating the severe limitations of using the simple signal-to-noise ratio (SNR) formalism for processes with non-Gaussian-distributed probability density functions. These results are valuable for guiding approaches to computational observers of signal data by showing the range of validity of suboptimal decision functions that are much easier to compute than the exact likelihood ratio solution. PMID- 7860824 TI - A computational model for signal processing by the dorsal cochlear nucleus. I. Responses to pure tones. AB - Much information is available on the anatomical organization and neurophysiological properties of the major cell types in the dorsal cochlear nucleus (DCN). The complicated response properties of individual cells and units in the DCN indicate that substantial information processing already occurs at the level of the DCN. A large number of connectional hypotheses have been put forward to explain various aspects of the response characteristics of DCN cells, but many of the consequences of these hypotheses have not been investigated quantitatively. In this paper, we investigate these hypotheses by constructing and testing mathematical and computational models and compare our results to those of previous modeling studies. The simplest versions of our models include auditory nerve (AN) fibers, type II cells (inhibitory interneurons) and type IV cells (fusiform and giant cells). The model response maps, i.e., the pattern of output of model type IV cells, generated by the simplest model have some but not all the features of the experimental response maps of type IV neurons. In particular, the excitatory region which occurs at best frequency is not isolated and the excitatory region at low frequencies and high amplitude is narrower than observed. Since experimental evidence exists that some of the connections between these cell types are divergent or convergent across adjacent isofrequency sheets, the effect of such convergence and divergence was then investigated. Response maps so obtained reproduce many of the qualitative features of the experimental maps. Enlargement of the model by including inhibitory interneurons (e.g., stellate cells) that receive convergent input from AN fibers and which inhibit type II cells results in the generation of response maps that, with some variations in connectional patterns and physiological properties of neurons, match most of the essential features seen in the large variety of experimental maps obtained from the cat DCN. PMID- 7860825 TI - A spatial feature extraction and regularization model for the head-related transfer function. AB - A functional representation is proposed for complex valued (amplitude and phase) head-related transfer functions (HRTFs), including both frequency and spatial dependence. The frequency variation is spanned by a set of eigentransfer functions (EFs) that are generated using the Karhunen-Loeve expansion. Any HRTF is represented as a weighted combination of the EFs where the weights are functions of the HRTFs spatial location and are termed spatial characteristic functions (SCFs). Samples of the SCFs are obtained by projecting the measured HRTFs onto the EFs. A regularization framework is employed to obtain a functional representation for the SCFs by fitting each set of SCF samples with a two dimensional spline. Acoustic validation of the model's fidelity and predictive capability is provided using 2188 measured HRTFs from a KEMAR manikin and 1816 measured HRTFs from an anesthetized live cat. Errors between measured and modeled HRTFs are generally less than one percent. Larger errors occur in the contralateral regions for KEMAR and lower back regions for the cat as a consequence of the relatively small HRTF amplitudes resulting from head shadowing. Methods for reducing these errors are discussed. PMID- 7860826 TI - Effect of frequency transposition on the discrimination of amplitude envelope patterns. AB - The effects of systematic training on listeners' ability to compare the amplitude envelopes of signals differing in frequency was tested. Listeners indicated which of two comparison signals had the same amplitude envelope as the target signal. During training, center frequencies of comparison signals were gradually increased or decreased relative to target signal center frequencies of 500, 1600, and 3160 Hz. After training, performance was still worse when target and comparison signals were at different frequencies rather than at the same frequency, except possibly when comparison signals were higher in frequency than the 1600-Hz target. Thus the amplitude envelopes of signals do not appear to be perceived independently of the signal itself. Listeners who received no training performed similarly to the trained listeners, except that their performances declined when comparison signals were higher in frequency than the 1600-Hz target. Training did not reduce interlistener differences in overall performance or in the extent of the decline in performance when frequency differences between the target and comparison signals were introduced. The effects of frequency lowering on amplitude envelope discrimination do not appear to be related to the reduced efficacy of frequency-lowered speech-derived amplitude envelopes in supplementing speechreading. PMID- 7860827 TI - Classification of background noises for hearing-aid applications. AB - A background-noise classification procedure is being developed for hearing-aid applications, wherein the hearing-aid response would be adjusted in response to changes in the noise environment. The classification procedure is based on measuring four signal features giving the fluctuations of the signal envelope and the mean frequency and low- and high-frequency slopes of the average spectrum. A more complicated procedure, based on determining the envelope modulation spectra in auditory critical bands, was also investigated and was found to offer no advantages over the simpler procedure. The accuracy of the classification procedure was determined for eleven everyday background noises under optimal conditions where the training and test noise sequences were different portions of the same short noise recording. A cluster analysis was used to determine the similarities among the feature vectors for the noises, and when the noises are grouped into a reduced number of clusters the noise-classification accuracy using the four features exceeds 90%. PMID- 7860828 TI - The supraglottal articulation of prominence in English: linguistic stress as localized hyperarticulation. AB - The results of an articulatory investigation of the supraglottal correlates of linguistic prominence in English, and a proposal of a unified description of linguistic stress are reported. Three models of stress are evaluated: that prominence expands jaw movement, that stress expands an abstract articulatory scale involving the opening and closing of the vocal tract, and that stress involves a localized shift toward hyperarticulate speech. A corpus of x-ray microbeam records of sensible speech is studied, within which the stress pattern is controlled and is checked by means of an intonational analysis. Jaw movement data yield similar results to earlier studies, but kinematic differences interpreted with reference to a gestural theory suggest that different subjects use different articulatory strategies to articulate stress contrasts. In addition, the jaw, lip, and tongue interact in the articulation of stress in subject dependent ways. Thus the articulation of stress should be formulated in terms of abstract articulatory goals, rather than in terms of individual articulator positioning. Finally, the data show that stress affects the articulation of nonsonority distinctions such as backness in vowels and point of articulation in consonants. A hyperarticulation model of stress is discussed in terms of these results. PMID- 7860829 TI - Modeling the glottal volume-velocity waveform for three voice types. AB - The purpose of this study was to model features of the glottal volume-velocity waveform for three voice types: modal voice, vocal fry, and breathy voice. The study analyzed data measured from two sustained vowels and one sentence uttered by nine adult, male subjects who represented examples of the three voice types. The primary analysis procedure was glottal inverse filtering, which estimated the glottal volume-velocity waveform. The estimated glottal volume-velocity waveform was then fit to an LF model waveform. Four parameters of the LF model were adjusted to minimize the mean-squared error between the estimated glottal waveform and the LF model waveform. Statistical averages and standard deviations of the four parameters of the LF glottal waveform model were calculated using the data for each voice type. The four LF model parameters characterize important low frequency features of the glottal waveform, namely, the glottal pulse width, pulse skewness, abruptness of closure of the glottal pulse, and the spectral tilt of the glottal pulse. Statistical analysis included ANOVA and multiple linear regression analysis. The ANOVA results demonstrated that there was a difference in three of the four LF model parameters for the three voice types. The linear regression analysis between the four LF model parameters and a formal rating by a listening test of the quality of the three voice types was used to determine the most significant LF model parameters for each voice type. A simple rule was devised for synthesizing the three voice types with a formant synthesizer using the LF glottal waveform model. Listener evaluations of the synthesized speech tended to confirm the results determined by the analysis procedures. PMID- 7860830 TI - Children learn separate aspects of speech production at different rates: evidence from spectral moments. AB - One theoretical perspective on speech development holds that segmental structure gradually emerges in the utterances of children as their first words, realized as roughly specified patterns of gesture, are differentiated into patterns of precisely specified and carefully coordinated gestures. The purpose of the present study was to test one aspect of this theoretical position, namely that children's articulatory gestures are not as precisely specified as are those of adults. In addition, a related hypothesis was tested, namely that some patterns of gesture achieve adultlike precision sooner than others. To test these hypotheses, the first, third, and fourth spectral moments were derived for fricative (/s/ and /integral of) and for stop-burst (/t/ and /k/) noises in the speech samples of children (3 to 7 years of age) and of adults. First spectral moments for fricatives showed stronger consonant effects (i.e., /s/ vs /integral of/) for adults' than for children's samples. This acoustic finding replicated a previous result [Nittrouer et al, J. Speech Hear. Res. 32, 120-132 (1989)], and provided support for the hypothesis that some articulatory gestures are not as precisely specified in children's speech as in that of adults. First spectral moments for /t/ and /k/ revealed no age-related differences in the magnitude of the consonant effect, providing support for the hypothesis that some gestures achieve mature status sooner than others. Although not a focus of the present study, it was also found that children's /k/ first moments varied more than adults' as a function of vowel environment (/i/, /a/, or /u/). Thus further support was obtained for a finding described elsewhere: For at least some articulatory gestures, there is greater influence of one on another for children's than for adults' speech [e.g., Nittrouer et al., J. Speech Hear. Res. 32, 120-132 (1989); S. Nittrouer, J. Speech Hear. Res. 36, 959-971 (1993)]. PMID- 7860831 TI - Further tests of the "perceptual magnet effect" in the perception of [i]: identification and change/no-change discrimination. AB - The present study investigated the existence of a "perceptual magnet" effect [Kuhl, Percept. Psychophys. 50, 93-107 (1991)] in a speech perception experiment. Sixteen subjects experienced in phonetics, transcribed the [i] stimuli used by Kuhl (1991) or identified the stimuli as [i] or not-[i] in experiment 1. In experiments 2 and 3, 50 adults who were not trained in phonetics, participated in an identification task requiring them to decide whether the vowel sounds they heard were the "[i] in 'peep'" or "not the [i] in 'peep'. "They also completed a "change/no change" discrimination task with standards consisting of the "prototype" [i] and other nonprototype stimuli at 67, 75, and 120 mels away from the prototype. Results from the first study showed that listeners did not identify the 120-mel token previously used by Kuhl (1991) as the nonprototype standard stimulus in discrimination experiments as [i]. Sensitivity results from experiments 2 and 3, as measured with d-prime partially supported the "perceptual magnet" hypothesis as suggested by Kuhl (1991) whereas miss results did not. Findings indicated that d-prime, a nonbiased measure of subjects' discrimination ability, better represented the perceptual magnet effect than misses alone. Thus results suggested that subjects were better able to discriminate stimuli surrounding a less "prototypical" [i] vowel as demonstrated by greater sensitivity, faster reaction times for hits and fewer number of misses. However, current results may also be explained by increased auditory resolution rather than prototype-based, "magnet" effects. It was concluded that whereas the perceptual magnet effect may exist for particular vowel categories, more data are needed to better understand the role of prototypes in speech perception. PMID- 7860832 TI - Mapping the perceptual magnet effect for speech using signal detection theory and multidimensional scaling. AB - Recent experiments have demonstrated that the category goodness of speech sounds strongly influences perception in both adult and infants [Kuhl, Percept. Psychophys. 50, 93-107 (1991); Kuhl et al., Science 255, 606-608 (1992)]. Stimuli judged as exceptionally good instances of phonetic categories (prototypes) make neighboring tokens in the vowel space seem more similar, exhibiting a perceptual magnet effect. Three experiments further examined the perceptual magnet effect in adults. Experiment 1 collected goodness and identification judgments for 13 variants of the vowel /i/. Experiment 2 used signal detection theory to assess the discrimination of these tokens using a bias-free measure (d'). Experiment 3 employed multidimensional scaling (MDS) to geometrically model the distortion of the perceptual space due to the magnet effect. The results demonstrated a strong relationship between category goodness and discrimination. Vowel tokens receiving high goodness ratings in experiment 1 were more difficult to discriminate in experiment 2 and were more tightly clustered in the MDS solutions of experiment 3. These findings support the existence of a perceptual magnet effect, and may help explain some aspects of first language learning in infants and second language learning in adults. PMID- 7860833 TI - Signal detection modeling of Japanese listeners' /r/-/l/ labeling behavior in one interval identification task. AB - This study tested the validity of applying a signal detection model to Japanese listeners' /r/-/l/ labeling behavior in one-interval identification task, and the hypothesis that Japanese listeners estimate each token's goodness of fit to Japanese /r/ in labeling it as /r/ or /l/. The identification data obtained by manipulating subjects' response criteria fit the signal detection model. The performance in the identification task was highly predictable based on the goodness of fit judgment, indicating that category goodness information contained in /r/ and /l/ is utilized in deriving underlying sensory decision variables. The data, however, also suggested that these variables are not a direct consequence of the goodness of fit judgment. Various implications of the signal detection model in the investigation of Japanese perception of /r/ and /l/ are discussed. PMID- 7860834 TI - The role of formant transitions in the perception of concurrent vowels. AB - When two voices compete for the attention of the listener, the spectral peaks that define the formants of one voice can be intermittently obscured or distorted by formants of the other voice. However, formant peaks vary slowly and continuously in frequency and time, providing a basis for tracking through regions of overlap. Three experiments investigated the ability of listeners to exploit formant-pattern continuity to segregate pairs of synthesized vowels that were presented simultaneously and monaurally. Experiment 1 and 2 examined the effects of introducing one member of the pair with formant-frequency transitions that specified syllable-initial glides /w/ or /j/. Identification accuracy was generally higher in conditions where glides were present. Gliding formants provided smaller benefits than a two-semitone difference in fundamental frequency between the vowels. Experiment 3 found larger effects of formant transitions specifying initial or final /l/. Overall, formant transitions did not make it easier to identify the vowel to which they were linked; instead, they helped by making the competing vowel more identifiable. One explanation for improvement in the glide conditions is a formant-tracking process which groups together the formants of each voice using the Gestalt principle of good continuation. However, this account predicts improvement for both vowels which was generally not observed. An alternative explanation is suggested by models that apply a brief, sliding temporal window to determine which region of the signal provides the strongest evidence of each vowel constituent. The formant transition region may provide a time interval during which the competing steady-state vowel is perceptually more prominent. PMID- 7860835 TI - Temporal envelope and fine structure cues for speech intelligibility. AB - This paper describes a number of listening experiments to investigate the relative contribution of temporal envelope modulations and fine structure to speech intelligibility. The amplitude envelopes of 24 1/4-oct bands (covering 100 6400 Hz) were processed in several ways (e.g., fast compression) in order to assess the importance of the modulation peaks and troughs. Results for 60 normal hearing subjects show that reduction of modulations by the addition of noise is more detrimental to sentence intelligibility than the same degree of reduction achieved by direct manipulation of the envelope; in some cases the benefit in speech-reception threshold (SRT) is almost 7 dB. Two crossover levels can be defined in dividing the temporal envelope into two equally important parts. The first crossover level divides the envelope into two perceptually equal parts: Removing modulations either chi dB below or above that level yields the same intelligibility score. The second crossover level divides the envelope into two acoustically equal peak and trough parts. The perceptual level is 9-12 dB higher than the acoustic level, indicating that envelope peaks are perceptually more important than troughs. Further results showed that 24 intact temporal speech envelopes with noise fine structure retain perfect intelligibility. In general, for the present type of signal manipulations, no one-to-one relation between the modulation-transfer function and the intelligibility scores could be established. PMID- 7860836 TI - How young and old adults listen to and remember speech in noise. AB - Two experiments using the materials of the Revised Speech Perception in Noise (SPIN-R) Test [Bilger et al., J. Speech Hear. Res. 27, 32-48 (1984)] were conducted to investigate age-related differences in the identification and the recall of sentence-final words heard in a babble background. In experiment 1, the level of the babble was varied to determine psychometric functions (percent correct word identification as a function of S/N ratio) for presbycusics, old adults with near-normal hearing, and young normal-hearing adults, when the sentence-final words were either predictable (high context) or unpredictable (low context). Differences between the psychometric functions for high- and low context conditions were used to show that both groups of old listeners derived more benefit from supportive context than did young listeners. In experiment 2, a working memory task [Daneman and Carpenter, J. Verb. Learn. Verb. Behav. 19, 450 466 (1980)] was added to the SPIN task for young and old adults. Specifically, after listening to and identifying the sentence-final words for a block of n sentences, the subjects were asked to recall the last n words that they had identified. Old subjects recalled fewer of the items they had perceived than did young subjects in all S/N conditions, even though there was no difference in the recall ability of the two age groups when sentences were read. Furthermore, the number of items recalled by both age groups was reduced in adverse S/N conditions. The resutls were interpreted as supporting a processing model in which reallocable processing resources are used to support auditory processing when listening becomes difficult either because of noise, or because of age related deterioration in the auditory system. Because of this reallocation, these resources are unavailable to more central cognitive processes such as the storage and retrieval functions of working memory, so that "upstream" processing of auditory information is adversely affected. PMID- 7860837 TI - Objective speech quality assessment and the RPE-LTP coding algorithm in different noise and language conditions. AB - The formulation of reliable signal processing algorithms for speech coding and synthesis require the selection of a prior criterion of performance. Though coding efficiency (bits/second) or computational requirements can be used, a final performance measure must always include speech quality. In this paper, three objective speech quality measures are considered with respect to quality assessment for American English, noisy American English, and noise-free versions of seven languages. The purpose is to determine whether objective quality measures can be used to quantify changes in quality for a given voice coding method, with a known subjective performance level, as background noise or language conditions are changed. The speech coding algorithm chosen is regular pulse excitation with long-term prediction (RPE-LTP), which has been chosen as the standard voice compression algorithm for the European Digital Mobile Radio system. Three areas are considered for objective quality assessment which include: (i) vocoder performance for American English in a noise-free environment, (ii) speech quality variation for three additive background noise sources, and (iii) noise-free performance for seven languages which include English, Japanese, Finnish, German, Hindi, Spanish, and French. It is suggested that although existing objective quality measures will never replace subjective testing, they can be a useful means of assessing changes in performance, identifying areas for improvement in algorithm design, and augmenting subjective quality tests for voice coding/compression algorithms in noise-free, noisy, and/or non-English applications. PMID- 7860839 TI - Modeling acoustic backscatter from kidney microstructure using an anisotropic correlation function. AB - Techniques for investigating acoustic backscatter from anisotropic biological tissues are examined. This empirical study combines single-scatter theory with the known elastic properties and histology of the renal cortex to predict the backscatter coefficient from kidney parenchyma. A transverse isotropic correlation model is developed to explain how backscattered energy, which varies with the incident sound wave direction, is related to the anisotropic structure of the tissue. From the results we conclude that renal morphology scatters sound incoherently, and that complex mixtures of scattering structures of different sizes, number densities, and scattering strengths can be distinguished by analyzing backscatter in specific frequency channels--a spectroscopic approach. A K-space description of backscatter measurements from kidney cortex, including the effects of anisotopy, provides further support of our hypothesis regarding sources of acoustic scattering. PMID- 7860838 TI - Speech intelligibility assessment in a helium environment. AB - The purpose of this study was to compare the appropriateness and effectiveness of the speech perception in noise (SPIN) test and the Griffiths version of the modified rhyme test (GMRT) in assessing Navy divers' speech understanding using communication systems containing different helium speech unscramblers (HSUs), one of which produces, by subjective observations, more intelligible output than the other. Divers participating in a saturation deep dive and a group of nondivers using digital audio tape recordings of the stimuli used by the divers were tested. Mean percent correct scores on the SPIN and GMRT lists within two listening conditions (taped, topside-diver and live-voice, diver-diver) were almost identical. Listeners scored better on both tests in the topside-diver condition than in the diver-diver condition. The majority of the SPIN errors were on low-predictability items that are void of context. Context clearly played a role in measuring the performance of these subjects, at least for the SPIN test. No significant differences were measured between the two HSUs, although a trend was seen favoring one HSU over the other for the divers. These results have theoretical as well as practical value for measuring the quality and intelligibility of helium speech enhancement systems. PMID- 7860840 TI - A proposed microscopic elastic wave theory for ultrasonic backscatter from myocardial tissue. AB - The physical structures responsible for ultrasonic scattering from myocardial tissue have not yet been conclusively defined. It is hypothesized in this paper that the backscatter from myocardium is primarily due to inhomogeneities approximately the size of the myocytes. In particular, it is proposed that the acoustic contrast responsible for the scattering is that between the extracellular collagen network that surrounds each myocyte (or myocyte bundle) and the rest of the tissue (the myocytes' intracellular contents). To test this hypothesis, a simple elastic wave scattering model for myocardium was developed. An elementary scatterer is modeled as an ellipsoidal shell, having the material properties of wet collagen, imbedded in a host medium having the average properties of myocardium. The first Born approximation to elastic scattering is used to calculate the frequency-dependent scattering from a single scatterer. To scale up from a single scatterer to a distribution of scatterers, it is assumed that the power received at the transducer is simply the sum of the power scattered in the direction of the transducer by each individual scatterer located in the active volume of the beam (an independent-scatterer approximation). Calculations are restricted to the backscattering direction (pulse-echo), although the theory can accommodate pitch-catch scattering at all angles. With the aid of a computer program, the acoustic backscatter coefficient is calculated using the Born formalism and then measurement effects (frequency-dependent beam width and attenuation correction factors) are incorporated to arrive at calculated integrated (frequency-averaged) backscatter. Both the backscatter coefficient and integrated backscatter are calculated for angles of incidence that range from parallel to the long axis of the scatterer to perpendicular to this fiber direction. For the low MHz frequencies typically used in clinical echocardiography, the calculated absolute magnitude of the acoustic backscatter coefficient lies within a range from 0.0001 to 0.001 cm-1 sr-1. For selected fiber geometries, the anisotropy in integrated backscatter as the angle of incidence is varied with respect to the fiber orientation is about 10 dB. The predicted frequency dependence of the acoustic backscatter coefficient is calculated to be about f3.9 in the low MHz frequency range. These calculated results are reasonably consistent with published experimental measurements and provide a successful preliminary test of the hypothesis. PMID- 7860841 TI - Dimethylformamide as an enhancer of cavitation-induced cell lysis in vitro. AB - Polar solvents, including dimethylformamide (DMF), have been investigated as anticancer drugs, but their potential usefulness is constrained by hepatotoxic side effects. The ability to enhance drug cytotoxicity with ultrasound would be valuable in creating locally intense chemotherapy while minimizing effects peripheral to the treatment site. The effects of continuous wave ultrasound (US) (985 kHz; 0.5-2.5 W/cm2) were evaluated on cultured HL-60 human promyelocytic leukemia cells alone and with a noncytotoxic DMF dose (0.11 M). The cells were insonified in a configuration that created no cell lysis without the introduction of albumin-stabilized microbubbles into the exposure chamber. When microbubbles were introduced, US with bubbles induced cell lysis, and the presence of DMF significantly increased the lysis induced by ultrasound with bubbles. The necessary presence of microbubbles for the DMF-US synergism to occur suggests that a likely mechanism is acoustic cavitation, initiated by the presence of microbubbles as nuclei. Detection of subharmonics confirmed the presence of cavitation, and cell lysis was well correlated with the subharmonic amplitude. The results show that albumin-stabilized microbubbles, similar to those currently used as US contrast agents, may provide a significant source of nuclei and improve prospects for cancer therapy using acoustic cavitation. The evidence presented supports the hypothesis that cell damage is due to a sonochemical rather than to a sonomechanical process. PMID- 7860842 TI - Rise-time difference thresholds in the monkey. PMID- 7860843 TI - Failure to hear binaural beats below threshold. PMID- 7860844 TI - Nursing: an integration of art and science within the experience of the practitioner. AB - In this paper it is proposed that whilst nursing knowledge is underpinned by the philosophies of art and science they are integrated in such a way that nursing is greater than their sum and is thus a unique discipline. It begins with an exploration of the philosophies underpinning art and science, and their relationship to nursing. The discussion then moves on to examine critically the nature and development of theory in nursing with reference to art and science, the nursing knowledge thus generated and how that knowledge is learned and expressed. The paper concludes with an evaluation of how far the discipline of nursing lies within the paradigms of science and of art, and whether indeed art and science may be, to some extent, false distinctions. The authors conclude that nursing may be viewed as an integration of art and science, expressed through the practitioner's unique, yet also shared experience. PMID- 7860845 TI - A critical evaluation of the use of andragogical models in tackling social inequality in nursing education. AB - Issues related to inequalities within nurse education are explored by drawing on issues related to oppression and exploitation in general education, higher education and to the specific ways nurses (pre-registration and post-basic) are selected and taught. There is analysis of the way in which a holistic approach may be helpful in reducing inequalities, with specific reference being given to experiential learning and distance/open learning approaches. The role of the education system in creating and maintaining inequalities is explored in terms of rights, chances and educational outcomes. PMID- 7860846 TI - Electrical stimulation for the treatment of urinary incontinence: do we know enough to accept it as part of our practice? AB - While many nurses are involved in the treatment of incontinent patients, few are well-informed on electrical stimulation. In this paper, patient-controlled stimulation is discussed and implications for current nursing practice considered. The paper includes a discussion of the weaknesses in current research with electrostimulation and concludes with recommendations for future research in the treatment of incontinence with this new modality. PMID- 7860847 TI - Training and education for nurses working in neonatal care. AB - The issue of nurse education and training in the context of providing a high quality service for sick and small babies and their families is a paramount concern. As part of a large-scale study of neonatal nursing in the United Kingdom, data were collected on nurses' educational background, professional qualifications, experience, orientation, appraisal and update. The results reveal a qualification in specialty (QIS) rate for trained nurses of 53% and large variation not directly related to size or type of unit. The proportion of nurses having appraisal interviews (47% in the last year) and professional development plans (19%) was low and a clear gap existed between policy and practice. The implications of the findings are discussed and the need for management training, targeting of neonatal units with low QIS rates, and more flexible education programmes are emphasized. PMID- 7860848 TI - The student nurse selection experience: a qualitative study. AB - A qualitative study was undertaken to explore the experiences of student nurses recruited to three British colleges of nursing. A series of focus groups was initiated to discuss the career decisions surrounding their entry into nursing and their experiences of the selection interview. Similar groups were conducted with those who are involved in the selection of candidates for nursing to determine what influenced their decisions to accept or reject people. Analysis of the data suggests that nursing is attracting people from careers that are unstable or unsatisfactory. Selection procedures are outdated and inconsistent and interviewees quickly learn to provide appropriate responses. There is confusion surrounding the skills and qualities required of potential nurses, and more effective recruitment strategies might attract potential undergraduates without losing those with vocational aspirations. A more systematic approach to selection, using a range of objective, measurable criteria, may remove the intuitive selection of nurses, increasing the efficiency of the selection process. PMID- 7860849 TI - Intraprofessional teamwork in district nursing: in whose interest? AB - The purpose of this paper is to examine intraprofessional teamworking between district nurses. Data from an exploratory study, conducted in the United Kingdom, of 130 home visits of 16 district nurses describes intraprofessional relationships in community nursing teams. Participant observation and in-depth interviews were the methods of data collection. The findings suggest that the professional culture of community nursing has led to the development of organizational rules which, in a quest to avoid conflict between team members, potentially militate against patient choice. The data presented here explore three areas of the nurses' practice: committing services, changing care and working unsocial hours. PMID- 7860850 TI - Job satisfaction of community nurses working with people with a mental handicap. AB - There is a dearth of studies on the job satisfaction of community nurses, especially those working with people with a mental handicap, in the United Kingdom. This paper reports on some of the data gathered as part of a survey of community nurses (mental handicap) (CNMH) in Northern Ireland in 1992. A 25-item questionnaire was sent to all 50 CNMH. The response rate was 72%. The results showed that most of these CNMH rated their level of satisfaction as high or very high. Additionally, they identified a number of factors which contributed to their job satisfaction and/or dissatisfaction. These findings have implications for theory building, methodology and nursing practice. PMID- 7860851 TI - From special hospital to regional secure unit: a qualitative study of the problems experienced by patients. AB - For those patients in the United Kingdom who are compulsorily detained in a special hospital the most common route of release is via other psychiatric hospitals, especially regional secure units. That a large percentage of these patients are subsequently readmitted (43% in this study) indicates that they experience problems within the regional secure unit. A grounded theory approach was used to investigate this experience from the patients' perspective by interviewing a sample of 14 patients who had been readmitted to one special hospital. Data analysis can prove difficult in grounded theory and the approach that was used--a variant of the constant comparative method--is described. A number of inductively developed categories were generated from the interview data and one category is reported here. From these categories a theory of 'failure' is postulated that, it is contended, both describes and explains the process of readmission. Finally, the implications for practice in terms of the preparation of patients for transfer are addressed. PMID- 7860852 TI - Resettlement without the support of an ethnocultural community. AB - The purpose of this phenomenological study is to describe the lived experience of immigrating to a region where there is no ethnocultural community of one's culture. Twenty culturally isolated immigrants to Moncton, New Brunswick, Canada, of different ethnic origins were interviewed in depth about their resettlement experience: the Giorgi modification of the phenomenological method was used to analyse these data. The findings suggest that being a culturally isolated immigrant entails a sense of discontinuity between the past and the present and produces a period of heightened sensitivity to others. Informants felt propelled from their country into an alien environment and were suddenly immersed into a new culture. Their emotional energies were directed towards getting a foothold in their new society. This was a highly stressful process that was both encouraged and discouraged by pervasive thoughts of the future which permeated the participants' existence. PMID- 7860853 TI - Dietary calcium intake in 18-year-old women: comparison with recommended daily intake and dietary energy intake. AB - Average dietary calcium intake and energy intake of 113 18-year-old university students in Western Australia was examined. Four-day, weighted diet records, including 1 weekend day, were completed by the subjects. A large proportion of the students (68%) had an average daily calcium consumption below the 800 mg recommended by the National Health and Medical Research Council of Australia. A strong positive association was also found between dietary calcium and dietary energy intakes. Many young women on self-imposed energy reduction diets are at risk of a dietary calcium intake deficit at a time when it should be enhanced. These findings are significant for nursing practice as they indicate the need for further health education concerning the importance of dietary calcium in young women. PMID- 7860854 TI - Stress in cancer nursing: does it really exist? AB - Nursing cancer patients has been identified as a particularly stressful occupation. However, most studies have been descriptive, and few have measured levels of stress. A study was set up to identify cancer nurses' general proneness to stress and characteristics of nurses who experience the most stress. Sixty five registered nurses working on six wards in two hospitals identified the two most stressful incidents over the last 3 months and completed the Spielberger State-Trait Anxiety Inventory over an 8-week period. The state anxiety subscale was completed six times, the trait anxiety once. Data were analysed using SPSXX. Statistical tests included analysis of variance and the Kendall tau correlation coefficient. The nurses' general anxiety proneness was no different from the normal values for working females, and their overall state anxiety levels were only significantly higher than the normal values for working women under examination conditions on the first time of testing. Newly qualified nurses had a tendency to be more anxious compared with sisters and enrolled nurses. Most nurses reported high levels of job satisfaction. However, there was a statistically significant difference in nurses' anxiety levels between wards. The results suggest overall that the nurses in this sample were not experiencing high levels of stress. They were perhaps only stressfully satisfied. PMID- 7860855 TI - Patient perceptions of nursing care: an emerging theory of interpersonal competence. AB - Nurse-patient interactions were examined to identify elements of interpersonal competence among nurses from the perspective of patients. Forty patients and 12 nurses participated in this qualitative study at a private acute care hospital. Two-hundred and forty-five observations were completed. Open-ended questions were utilized in 85 audio-taped semi-structured interviews. Data collection and analysis occurred simultaneously using the constant comparative method. Four major processes emerged from the data to provide the framework for the themes: 'translating', 'getting to know you', 'establishing trust', and 'going the extra mile'. In the 'translating' theme, patients expressed satisfaction with the nurse patient interaction when nurses informed, explained and instructed on specific aspects of treatment, and taught general principles of care. The nurses' personal sharing, kidding and clicking appeared as important processes in 'getting to know you'. Patients reported confidence and trust when nurses took charge and appeared to enjoy their work. The theme of 'going the extra mile' included friendship and providing care beyond that expected. The processes provide a framework for an emerging theory of interpersonal competence. PMID- 7860856 TI - On the moral nature of nursing practice. AB - Until recent times many nursing authors have relied on rather narrow interpretations of selected aspects from the broader discourse of ethics and moral philosophy in their writing on ethics in nursing. As a consequence, discourse in nursing ethics has been limited in its vision and far from comprehensive in its content. This can be seen in the large number of texts and journals which discuss issues in nursing ethics. Particularly in many of the nursing textbooks up to and including the 1960s, 1970s and, to a lesser extent, the early 1980s, ethics content is commonly framed in terms of the dilemmas of practice. Moreover, overall there is a preoccupation with either deontological or teleological positions and the application of corresponding analytical frameworks consistent with the particular view taken. In most texts the preferred view is deontological, with a predominating emphasis on principle and duty. Recently in nursing ethics there has been a focus towards the deconstruction of the dominant views in ethics encompassed by the more traditional perspectives. Consequently, as in other areas of applied and theoretical ethics, there has been a re awakening of interest in the 'virtues', and in processes which encourage the articulation of ethical dimensions of practice in ways other than applying principles, rules and formulae to situations of clinical dilemma. PMID- 7860857 TI - Casualty nurses' attitudes to attempted suicide. AB - This study explores the attitudes of casualty nurses to attempted suicide. The nurses' age and length of experience in casualty were the independent variables. A total of 142 nurses from 11 hospitals in Northern Ireland had questionnaires circulated to them, with a 66.9% response rate. There were significant differences on four of the variables in relation to nurses' ages, and on two of the variables in relation to the nurses' length of experience in casualty. The older and the more experienced nurses seem to have more positive attitudes than the younger or the less experienced nurses. However, further nursing research, in Northern Ireland, is needed to corroborate these findings. Other recommendations are made. PMID- 7860858 TI - Concepts in nurse education. AB - This paper reports a case study of student and senior nurses at the Royal Free Hospital, London, England. Qualitative methods were used to investigate the perceptions of nursing upon which students and senior nurses based their activities on the wards. Differences were identified between the ways in which students and senior nurses 'saw' their day-to-day tasks. Analysis showed that these differences were based upon differing levels of conceptualization. Student nurses were found to operate with low levels of conceptualization and were thus unable to categorize or group the patients, procedures or problems confronting them. Senior nurses, on the other hand, operated with a high level of conceptualization and were able to perceive similarities in objects, events and processes and to differentiate these into categories, classes or patterns. This allowed them to prioritize lines of action and to respond to situations in a rational and effective way. The problem for nurse education, then, is how best to enable students to develop a professional level of conceptualization. Strategies are identified by which senior nurses might enable student nurses to develop concepts in relation to their nursing activities on the wards. PMID- 7860859 TI - Learning to nurse in the clinical setting. AB - The findings reported in this paper are part of a larger study examining student socialization into nursing. In analysing the data, it became evident that two major factors influenced the students' learning in the clinical setting: the first was the clinical instructor, the second peer support. Instructors who were organized, encouraging, outgoing, and who had good relationships with students, patients and nursing staff were seen as 'good' role models. When instructors were unable to establish rapport on a unit, negative feedback from nursing staff could be detrimental to student learning. Peer support encompassed three dimensions: facilitating learning, providing emotional support, and assisting with physical tasks. There was evidence that practising faculty had a stronger influence in shaping students' attitudes towards nursing than classroom teachers. PMID- 7860860 TI - The concept of vulnerability in relation to child protection: health visitors' perceptions. AB - The aim of this paper is to describe part of the findings of a study which explored the health visitor's role in identifying and working with vulnerable families in relation to child protection. The study was conducted using a broadly qualitative approach. A two-stage approach was undertaken to explore the concept of vulnerability and to assess health visitors' work in this area of practice. In stage one a postal survey of 102 health visitors was conducted with a response rate of 58 (57%). In stage two 12 in-depth interviews were completed with health visitors. This paper outlines one major aspect of the findings and focuses specifically on health visitors' perceptions about the concept of vulnerability and its relevance to child protection work. The analysis suggests that vulnerability is a nebulous, transient and complex concept influenced by multiple interacting factors. The existence of a continuum of vulnerability is clearly evident. It appears that families move in and out of vulnerability at various stages of the life cycle and this is largely dependent on 'internal' and 'external' stress factors and coping ability. This paper contributes to the knowledge base of vulnerability and raises a number of issues for health visiting practice. PMID- 7860861 TI - Nurses' attitudes and concerns to HIV/AIDS: a focus group approach. AB - An exploratory qualitative study was instigated to further identify nurses' attitudes to the care of people with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). This follows as a sequel to a study using a questionnaire. Data were collected from nine focus groups attended by a total of 29 nurses at a hospital within a New Zealand regional health authority. The principal findings suggest that nurses' attitudes to this patient group are varied and depend on social influences, personal experiences and the extent of knowledge regarding HIV/AIDS. Other concerns raised included nurses' rights to choose to care for HIV-positive patients and the issue of universal precautions. These findings may have implications for further educational initiatives and formation of hospital policy. PMID- 7860862 TI - Beyond measurement: fourth-generation evaluation in nursing. AB - Whoever believes that the 'scientific' method should not be the sole approach to quality assurance and evaluation research may be attracted to fourth-generation evaluation. The first three generations of evaluation have been categorized as 'measurement-orientated', 'objective-orientated' and 'judgement-orientated', whereas fourth-generation evaluation is 'negotiation-orientated'. In the present paper the author embarks on a description of these generations and makes suggestions for the implementation of fourth-generation evaluation in the health care setting. The appeal of fourth-generation evaluation is that it argues for all 'stakeholders' to have a right to place their claims, concerns and issues on the negotiating table. The evaluator acts as a facilitator of the evaluation process. 'Stakeholders' refers to all people in the setting who are affected by the evaluation, including managers, evaluators, medical and nursing staff. Participation of patients/clients is central in the negotiation process. PMID- 7860863 TI - Nursing for change: the orientations and values of Project 2000 diploma and undergraduate nursing students. AB - The introduction of pre-registration nursing degree and diploma programmes in the United Kingdom has provoked considerable scrutiny of a range of issues such as funding arrangements, links between colleges of nursing and midwifery and higher education and the impact of the new courses on education and service provision. Less attention has been devoted to the changing orientations and values of diploma and undergraduate students during their courses of study. The parallel commencement in 1991 of 3-year undergraduate and diploma programmes in Leicestershire provided an opportunity to chart the changing orientations (personal, political, ethical, professional and academic) of two cohorts of students matched by age, gender and branch programme. Research is being undertaken, a primary aim of which is to assess the changes that occur in these orientations over time and to relate these to the educational progression of the students through successive phases of their respective courses. The focus of the research concerns the student's personal experience and developing insights into health, nursing and care delivery. This paper seeks to provide an overview of the literature relevant to the study. PMID- 7860864 TI - Interpersonal learning in groups: an investigation. AB - The dissatisfaction of patients with communication in health care has largely been addressed by providing more communication skills training. Research into why skills training might be ineffective has identified various factors, which include organizational resistance, personal defences against anxiety and a need for personal reflection and support. In one college of nurse education small group discussion and reflection had become established practice for students in their first and second clinical experience. The groups met once weekly and were facilitated by a nurse teacher. Discussion was unstructured and focused on the nurse's interpersonal relationship with his or her patients. This project examined one such group and sought to examine the use of small group reflective discussion by nurses about their patients as a means of improving interpersonal communication. The research was conducted over a period of 6 months with nine student nurses meeting once weekly during their first two episodes of clinical experience. Kelly's personal construct theory was used and two repertory grids were constructed by the group. One grid examined processes and change in intrapersonal construing, and the other grid examined processes and change in construing about certain patients. These grids were completed by the students at the beginning and at the termination of the groups. Notes were taken after each group meeting, which recorded impressions and processes; these were discussed once weekly with supervision. The notes were analysed using a grounded theory methodology. The results show some changes in patterns of constructing in relation to self which indicate an increase in anxiety and reluctance to self reflect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7860865 TI - The politics of nursing: a framework for analysis. AB - The phrase the 'politics of nursing' has become part of the language of the nursing profession. However, the meanings attributed to this phrase in the literature are not always clear. The difficulties involved in arriving at an accurate definition of the term are discussed and the suggestion is made that this emerging area of study would be advanced if greater accuracy, in using the terminology, was employed when discussing and researching nursing politics. A framework, drawing on approaches that have been taken to address similar problems in the study of power, is proposed as a means of arriving at 'tighter' definitions for the terms involved. The conclusion is that if a degree of conceptual clarity is introduced, the work to expand the field of knowledge can progress in a more systematic way through the investigation of specific areas and levels of interrelated political activity. The debate is at an early stage and more work is needed to increase our understanding of this phenomenon. PMID- 7860866 TI - Long-term care reform in Alberta, Canada. Alberta's resident classification system: fact, fiction and future prospects. PMID- 7860867 TI - Commitment to nursing: the quest for quality education and practice. PMID- 7860868 TI - Geriatric nursing: an idea whose time has gone? A polemic. AB - The future role of the nursing profession in providing health care for older people is considered. It is argued that, despite claims to holism, nursing has maintained a narrow focus, concentrating mainly on acute hospital care. The concepts of professional protectionism and professional reductionism are used to explain the manifest failure of nursing and other professions working with older people and their carers to place the needs of their clients at the top of their agendas. A reorientation of nursing practice is advocated in order that the profession fulfils its potential with respect to older people. PMID- 7860869 TI - Staff nurses' work satisfaction in psychogeriatric wards. AB - This paper begins by reviewing the small number of studies of staff nurses' work satisfaction. Subsequently, an examination is made of the differences in work satisfaction between staff nurses and other grades of nursing staff in psychogeriatric wards in National Health Service hospitals in Scotland. These data are part of a larger study into work satisfaction and the quality of care in these settings. Significant differences in satisfaction at work are identified between the staff nurse group and the other grades taken as a whole. Analysis of the components of job satisfaction suggests that these differences arise from: first, the experience of the work itself; second, the quality of the supervision which takes place; and third, the assessment of hospital policies, such as the transfer of staff to other wards. PMID- 7860870 TI - Attention deficit disorder in college students: facts, fallacies, and treatment. AB - Attention deficit disorder (ADD), with or without hyperactivity, is a common but highly misunderstood and frequently underdiagnosed condition in college students. It affects students' academic and social success and emotional development. ADD is an invisible impairment of cortical regulation of activity and impulse control that is often hereditary, is as common in women as in men, and does not subside or disappear at puberty. ADD increases the risk of drug abuse, delinquency, incarceration, job failure, marital discord, and divorce. In college students, ADD is amenable to treatment in a multimodal program combining medication; individual, family, and group psychotherapy; career counseling; and cognitive control, together with electronic prostheses and special accommodations in the college classroom. PMID- 7860871 TI - Prevention in college health: counseling perspectives. AB - Such problems as sexually transmitted diseases, alcohol and other drug use, and acquaintance rape require college health professionals to function in primary and secondary preventive roles. In this article, the authors draw upon counseling literature and college health practice to identify the central elements of preventive programs, highlight specific intervention formats used in preventive work, and describe how interventions are assembled into coherent programs of prevention. To illustrate the structure and process of long-range, institutionalized preventive efforts, the authors describe an initiative addressing the primary, secondary, and tertiary prevention of substance use at a health sciences campus. PMID- 7860872 TI - Graduate students' health insurance status and preferences. AB - A survey of graduate and professional students at the University of Michigan revealed that many (12.6%) do not have healthcare coverage. Minority students and students who are financing their education with loans and scholarships are at a particularly high risk of being uninsured. Students are divided in their preferences for changes in policies and systems of coverage. Most of the students' preference is for the university to offer a modestly improved plan and a requirement that students prove insurance coverage. In addition, some students indicated that they would like to have an inexpensive plan as well as the current system of voluntary insurance. After the survey, university officials opted to continue with current offerings and to add an improved policy under a voluntary system. PMID- 7860873 TI - A retrospective study of first sexual intercourse experiences among undergraduates. AB - Survey data concerning the first sexual intercourse (FSI) experiences of 272 undergraduate students revealed that 6% had experienced FSI against their personal wills (victims); 1% had experienced FSI against the will of the other person (offenders); 81% had experienced FSI at the will of both participants (consenting); and 11% were virgins (does not add up to 100% because of rounding). Examination of the students' perceptions of the various factors contributing to nonconsensual sexual intercourse (NSI) showed that fewer than 50% of the students agreed that situational and psychological factors contribute to NSI. Results also indicated that being a woman and perceptions about the factors that reduce victims' resistance were significant predictors of who would be the victim of FSI. Religious background, the reasons for having a date, and perceptions regarding the factors that enhance motivation to have NSI were significant predictors of FSI offenders. Personal risk behaviors were the strongest predictors of students who experienced FSI at the will of both participants, and risk factors were inversely related to being a virgin. PMID- 7860874 TI - Protocols constructed around the nursing process. 2: Oral contraceptives. AB - The author offers detailed procedures for RNs and NPs who provide oral contraceptives to students through a college health service. She includes an outline of necessary subjective assessments, objective examinations, and laboratory work, and includes a list of absolute contraindications, strong relative contraindications, and other situations that may indicate that it would be unwise to provide oral contraceptives to students. Interventions for the registered nurse and nurse practitioner are described and schedules for follow-up visits are given. PMID- 7860875 TI - On medical withdrawals for mental health reasons. PMID- 7860876 TI - Uncomplicated E coli urinary tract infection in college women: a retrospective study of E coli sensitivities to commonly prescribed antibiotics. AB - To determine the sensitivity of Escherichia coli organisms to various antibiotics, the authors conducted a 4-month retrospective chart study of 95 patients with urinary tract infection (UTI). They found great variation in sensitivity of E coli to the different antibiotics and concluded that amoxicillin and the cephalosporins are no longer effective first-line UTI treatments. Of the antibiotics evaluated, ciprofloxacin was the best choice, but both nitrofurantoin and TMP/SMX are less expensive and are effective for about 90% of uncomplicated UTIs. PMID- 7860877 TI - If it's not broken ... PMID- 7860878 TI - Is license exam a failure? PMID- 7860879 TI - Is license exam a failure? PMID- 7860880 TI - Is license exam a failure? PMID- 7860881 TI - Is license exam a failure? PMID- 7860882 TI - Is license exam a failure? PMID- 7860883 TI - Tobacco use. PMID- 7860884 TI - New and emerging technologies: promise, achievement and deception. AB - Technology has touched every aspect of dentistry from diagnosis to treatment. The promises and limitations of several emerging technologies, including lasers, digital radiology and electronic anesthesia, are reviewed. PMID- 7860885 TI - Integrating technology into dental practices. AB - The use of computers in dentistry has expanded considerably in the last 15 years. Computer software can facilitate practice activities ranging from patient data management and financial management to treatment planning and electronic scheduling. This article addresses strategies for using technology to simplify and improve practice management. PMID- 7860886 TI - The impact of gene therapy on dentistry. AB - To the casual observer, gene therapy--an emerging science--appears likely to have little impact on dentistry. However, even in these early research stages, it is clear that gene therapy will have a broad effect on dentistry. This article is designed to provide the practitioner with a general understanding of gene therapy, as well as several examples of how it is being used today in efforts to manage dental and oral problems better. PMID- 7860887 TI - Dental education at the crossroads: a report by the Institute of Medicine. AB - Today's dental schools confront an environment in higher education and health care that promises less stable financing and, thus, more uncertainty for faculty, students, researchers and administrators. A new report from the Institute of Medicine underscores the need for changes in dental education to prepare for a future that will in many important ways be quite different from the past. PMID- 7860888 TI - Evaluating chemical inactivation of viral agents in handpiece splatter. AB - The water spray used with a modern high-speed dental drill is a significant vehicle for dispersion of infectious agents into the environment, putting patients and the dental staff at risk of infection. This study examines whether disinfectants added to the handpiece water supply could inactivate viral contaminants in splatter. Results supporting use of ethanol or sodium hypochlorite are presented. PMID- 7860889 TI - Comparing E- and D-speed film: the effects of various storage conditions on fogging. AB - Despite the reduced radiation exposure documented with E-speed film use, many clinicians still prefer D-speed radiographic film. The authors tested various storage factors and found that E-speed film is more sensitive to these variables than D-speed film. PMID- 7860890 TI - Adjunctive caries control in overdenture abutment teeth: a new modality. AB - Controlling caries in decoronated abutment teeth is an ongoing concern for the restorative dentist. In the ideal situation, the overdenture abutment is restored with a cast coping, but economic constraints may rule this out in favor of a prefabricated overdenture attachment. This article describes how caries may be controlled in exposed dentin when such a restoration is used. PMID- 7860891 TI - Multiple episodes of angioedema associated with lisinopril, an ACE inhibitor. PMID- 7860892 TI - Bite marks in forensic dentistry: a review of legal, scientific issues. AB - Bite marks are an important and sometimes controversial aspect of forensic odontology. The discipline has recently received considerable attention in the media and in scientific realms. Although there are many cases in which bite mark evidence has been critical to the conviction or exoneration of criminal defendants, there is continuing dispute over its interpretation and analysis. This article explores the legal and scientific basis of bite mark evidence. PMID- 7860893 TI - Arteriovenous malformation of the mandible: life-threatening complications during tooth extraction. AB - This case illustrates how a vascular malformation can turn an ordinary tooth extraction into an emergency situation. Arteriovenous malformations are rare and difficult to detect on radiographs. Early warning signs are discussed and surgical treatment is described. PMID- 7860894 TI - A void in U.S. restorative dentistry. PMID- 7860895 TI - Dental splint prescription patterns: a survey. AB - A random sample of U.S. dentists was surveyed with a mailed questionnaire to determine the number of splints that they fabricated over the preceding year for bruxers, patients with myofascial pain-dysfunction syndrome and patients with TM joint pain. The results indicate that a significant number of dentists treat these disorders with dental splints. Estimates are provided for the dental profession's yearly splint output for each disorder. PMID- 7860896 TI - International comparison of waiting times for selected cardiovascular procedures. AB - OBJECTIVES: This study was designed to compare waiting times for cardiovascular procedures in five different health care delivery/financing systems. BACKGROUND: A recurrent criticism of national health care systems is long waiting times, or "queues," for high technology procedures. However, no objective data exist comparing waiting times in the United States with those in other systems. METHODS: Directors of cardiac catheterization laboratories, directors of cardiac surgery in the United States, U.S. Department of Veterans Affairs (VA) system, Canada and the United Kingdom and directors of cardiology clinics in Sweden were asked to respond to a mailed questionnaire as to how long it would take to obtain coronary angiography or coronary artery bypass surgery, or both, for specified case scenarios at their institutions. RESULTS: Significant differences in waiting times (p < 0.00001) were found among the systems for all four scenarios (elective and urgent angiography, elective and urgent bypass surgery). Compared with non-VA hospitals in the United States, waiting times were significantly longer in all systems, with the exception of waiting times for urgent surgery in the U.S. VA hospitals (p = 0.9). The longest waiting times for all four procedures were reported in the United Kingdom, Sweden and Canada, with some waiting times for elective procedures > 9 months. CONCLUSIONS: Physicians report that patients treated in health care systems structured differently from the non-VA hospital system in the United States wait significantly longer for cardiac catheterization and coronary artery bypass surgery. PMID- 7860897 TI - International comparisons of waiting times for cardiovascular procedures: a commentary on the long queue. PMID- 7860898 TI - Relation of initial infarct size to extent of left ventricular remodeling in the year after acute myocardial infarction. AB - OBJECTIVES: This study attempted to determine the relation between infarct size after acute myocardial infarction and subsequent left ventricular remodeling using precise clinical measurements. BACKGROUND: Animal studies have demonstrated that the degree of left ventricular remodeling after myocardial infarction is linearly related to infarct size. Clinical studies have not clearly replicated these results because of imprecise measurements and failure to adjust for patency of the infarct-related artery. METHODS: Infarct size was measured from technetium 99m (Tc-99m) sestamibi perfusion images in 14 patients (12 with an anterior, 2 with an inferior infarction) by a threshold method previously described and expressed as percent of the left ventricle (32 +/- 17% left ventricle [mean +/- SD], range 6% to 58%). Absolute end-systolic volume, end-diastolic volume and ejection fraction were determined by electron beam computed tomographic images performed at discharge and at 6 weeks, 6 months and 1 year after myocardial infarction. All patients had documented infarct-related artery patency after reperfusion therapy. RESULTS: At hospital discharge, there was no correlation between infarct size and end-systolic and end-diastolic volumes or ejection fraction. There was significant left ventricular dilation in the study group over the next year. As remodeling progressed, there was closer correlation between infarct size and ejection fraction and end-systolic volume measures (infarct size vs. end-systolic volume, from r = 0.43 at discharge to r = 0.80 at 1 year; infarct size vs. ejection fraction, from r = -0.39 at discharge to r = -0.84 at 1 year). There was a strong inverse correlation between infarct size at discharge and subsequent changes over the next year in end-systolic volume (r = 0.63, p = 0.02) and ejection fraction (r = -0.66, p = 0.01). CONCLUSION: Infarct size as measured by Tc-99m sestamibi at hospital discharge after an index infarction is predictive of subsequent change in left ventricular volume and function in the year after myocardial infarction. Patients with a large infarct demonstrated the greatest degree of dilation in the setting of patency of the infarct-related artery. PMID- 7860899 TI - Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute myocardial infarction. Analysis of 28 months of follow-up in 196 patients. AB - OBJECTIVES: We sought to determine the incidence and independent prognostic value of increased serum levels of sensitive serologic markers in patients in whom a conventionally diagnosed acute myocardial infarction had been ruled out. BACKGROUND: Increased serum levels of creatine kinase (CK) isoenzyme MB mass and cardiac troponin T in patients with unstable angina pectoris are associated with a poor prognosis. METHODS: We analyzed data from 196 consecutive patients with suspected acute myocardial infarction, which was later ruled out in 124. Increased serum levels of CK-MB mass, troponin T and myosin light chains were compared with clinical findings, ST-T wave abnormalities and presence of arrhythmias. RESULTS: Of the patients in the noninfarction group, 28% had serum CK-MB mass > or = 6 micrograms/liter, 20% had troponin T > or = 0.20 micrograms/liter, and 26% had myosin light chains > or = 0.4 micrograms/liter (discrimination limits). The cardiac event rate (cardiac death, nonfatal acute myocardial infarction) within 28 months was significantly higher in patients in the noninfarction group with elevated marker levels (range 22% to 24%) than in patients with values below these discriminators (range 3% to 5%) but was not significantly different from that in patients with a definite diagnosis of acute myocardial infarction (29%). Further, significant predictors of cardiac events were previous myocardial infarction; myocardial infarction or angina pectoris, or both; previous congestive heart failure; ST-T wave abnormalities on admission; a transient ST-T wave shift on serial electrocardiograms (ECGs); recurrent chest pain; and occurrence of supraventricular or ventricular tachycardia, or both, during the 1st 48 h after admission. It was found that all three biochemical markers, in the main, convey independent prognostic information with respect to clinical findings and presence of arrhythmias but not ST-T wave abnormalities on admission or a transient ST-T wave shift on serial ECGs. CONCLUSIONS: Increased serum levels of CK-MB mass, troponin T and myosin light chains all detect a subgroup of 25% of patients without acute myocardial infarction who have as poor a prognosis as that of patients with a definite diagnosis of acute myocardial infarction. All three biochemical markers provide similar important independent prognostic information with regard to clinical findings and arrhythmias but add no additional prognostic information once ECG ST-T wave changes are considered. PMID- 7860900 TI - Angiographic predictors of reocclusion after thrombolysis: results from the Thrombolysis in Myocardial Infarction (TIMI) 4 trial. AB - OBJECTIVES: This study attempted to determine which lesion characteristics are associated with reocclusion by 18 to 36 h. BACKGROUND: Reocclusion of the infarct related artery after successful reperfusion is associated with significant morbidity and up to a threefold increase in mortality. METHODS: Two hundred seventy-eight patients with acute myocardial infarction were randomized to receive either anisoylated plasminogen streptokinase activator complex (APSAC) or recombinant tissue-type plasminogen activator (rt-PA) or their combination. Culprit arteries were assessed for Thrombolysis in Myocardial Infarction (TIMI) flow grade, lesion ulceration, thrombus, collateral circulation and eccentricity. Minimal lumen diameter, percent diameter stenosis and lesion irregularity (power) were calculated using quantitative angiography. RESULTS: Reocclusion was observed more frequently in arteries with TIMI 2 versus TIMI 3 flow (10.4% vs. 2.2%, p = 0.003), in ulcerated lesions (10.7% vs. 3.0%, p = 0.009) and in the presence of collateral vessels (18.2% vs. 5.6%, p = 0.03). Similar trends were observed for eccentric (7.3% vs. 2.3%, p = 0.06) and thrombotic (8.4% vs. 3.3%, p = 0.06) lesions. Reocclusion was associated with more severe mean percent stenosis (77.9% vs. 73.9%, p = 0.04). Lesion length, reference segment diameter and Fourier measures of lesion irregularity were not associated with reocclusion. CONCLUSIONS: Several simply assessed angiographic variables, such as the presence of TIMI grade 2 flow, ulceration, collateral vessels and greater percent diameter stenosis at 90 min after thrombolytic therapy, are associated with significantly higher rates of infarct-related artery reocclusion by 18 to 36 h and may aid in identifying the subset of patients who are at significantly higher risk of early reocclusion and who potentially warrant further early pharmacologic or mechanical intervention. PMID- 7860901 TI - Technetium-99m sestamibi tomographic evaluation of residual ischemia after anterior myocardial infarction. AB - OBJECTIVES: This study investigated the value of sestamibi scintigraphy in assessing residual ischemia after anterior myocardial infarction. BACKGROUND: Serial imaging with sestamibi, the uptake and retention of which correlate with regional myocardial blood flow and viability, has been used to estimate salvaged myocardium and risk area after acute infarction. We recently documented that recovery of perfusion and contraction in the infarcted area may continue well after the subacute phase, suggesting myocardial hibernation. Some underestimation of viability in the setting of hibernating myocardium by sestamibi imaging has been reported. METHODS: We studied 58 patients in stable condition after Q wave anterior infarction. Regional perfusion and function were quantitatively assessed by sestamibi tomography and two-dimensional echocardiography at 4 to 6 weeks and at 7 months after infarction. In sestamibi polar maps, abnormal areas with tracer uptake > 2.5 SD below our reference values were computed at rest and after symptom-limited exercise. On two-dimensional echocardiography the ejection fraction and extent of rest wall motion abnormalities were assessed by a computerized system. All patients had coronary angiography between the two studies. RESULTS: At 7 months the extent of rest sestamibi defect was significantly reduced in 40 patients (69%, group 1) and unchanged in 18 (31%, group 2). Rest wall motion abnormalities and ventricular ejection fraction significantly improved in group 1 but not in group 2. Underlying coronary disease, patency of the infarct-related vessel and rest sestamibi defect extent at 5 weeks were comparable between the two groups. At 7 months, an increase in the reversible (stress-rest defect) tracer defect was observed in group 1 (p < 0.05) despite a smaller stress-induced hypoperfusion (p < 0.05). Reversible sestamibi defects and stress hypoperfusion were unchanged in group 2. In 38 (95%) of 40 group 1 patients, the area showing reversible sestamibi defects at 7 months matched the area showing fixed hypoperfusion at 5 weeks. CONCLUSIONS: The reduction in the rest tracer uptake defect that can occur late after infarction may affect the assessment of ischemic burden by sestamibi imaging early after anterior myocardial infarction. PMID- 7860902 TI - Relation of severity of symptoms to transient myocardial ischemia and prognosis in unstable angina. AB - OBJECTIVES: This study was undertaken to compare the relative power of the severity of angina versus that of any other clinical, electrocardiographic (ECG) and angiographic findings in predicting the risk of subsequent in-hospital coronary events in patients admitted to the coronary care unit for treatment of unstable angina. BACKGROUND: The presence or absence of chest pain has traditionally been used to guide management and therapy of unstable angina. However, recent studies raised the possibility that the cumulative duration of ischemia may be an additional index of prognosis. METHODS: We studied 104 consecutive patients admitted to the coronary care unit because of unstable angina. Diaries of symptoms were accurately kept. All patients underwent Holter ambulatory ECG monitoring during the 1st 24 h and angiography within 1 week of admission. RESULTS: During the hospital stay, 41 patients (group 1) had subsequent coronary events; the remaining 63 patients (group 2) had a good clinical outcome. Recurrence of chest pain after admission was observed in 76% of patients: 36 of the 41 group 1 patients (sensitivity 88%) and 43 of the 63 group 2 patients (specificity 32%). Anginal scores (frequency and persistence of pain, duration of each single episode and pain-free interval) showed high specificity but low sensitivity for detecting evolution toward subsequent coronary events. On Holter monitoring, the duration/24 h of the total number of ischemic episodes was consistently greater in group 1 than in group 2. A cumulative duration of ischemia > or = 60 min/24 h was observed in 34 of the 41 group 1 patients (sensitivity 83%) but in only 16 of the 63 group 2 patients (specificity 75%). High risk coronary artery lesions (left main coronary artery disease or complex stenosis) were detected in 36 of the 41 group 1 patients and in 26 of the 63 group 2 patients. CONCLUSIONS: Transient myocardial ischemia detected by Holter monitoring, but not chest pain, is the best predictor of unfavorable short-term clinical outcome. The decision to perform early angiography and revascularization cannot be based on symptoms alone. PMID- 7860903 TI - Optimal stage duration in dobutamine stress echocardiography. AB - OBJECTIVES: This study attempted to determine the benefit of a 5-min dobutamine stress echocardiographic stage versus a 3-min stage in a canine model. BACKGROUND: Dobutamine stress echocardiography, as currently performed, uses a variety of different protocols. Among the many aspects of dobutamine stress echocardiographic protocols that vary is stage duration. Because dobutamine has specific pharmacodynamics, it is possible that stages of different durations may have different cardiovascular effects. METHODS: Paired dobutamine stress echocardiograms were obtained in 10 open chest instrumented dogs. The stage duration for the initial dobutamine stress echocardiogram was randomly allocated to either 3 or 5 min, and all hemodynamic and echocardiographic variables were allowed to return to baseline before the second dobutamine stress echocardiogram was obtained using the alternative stage duration. At each stage, heart rate, systolic blood pressure, coronary flow, myocardial wall thickness and left ventricular cavity area were recorded. Cavity obliteration, hypotension, ventricular tachycardia or a maximal dose of 40 micrograms/kg body weight per min served as the dobutamine stress echocardiographic end point. RESULTS: At baseline, no difference was detected between the 3- or 5-min protocols for heart rate, systolic blood pressure, rate-pressure product, coronary blood flow, wall thickness or percent area change. Heart rate, systolic blood pressure and coronary flow increased more by the 10-micrograms/kg per min dose with the 5-min protocol than with the 3-min protocol. The dobutamine stress echocardiographic end points were achieved at a lower dobutamine dose (15.0 +/- 4.1 vs. 11.0 +/- 2.1 micrograms/kg per min [mean +/- SD], p = 0.01) with the longer stage duration. CONCLUSIONS: In this canine model, a longer stage produced a greater hemodynamic effect at a lower peak dose. Thus, extending stage duration in clinical dobutamine stress echocardiography may achieve equivalent physiologic stress at lower doses and contribute to the optimization of dobutamine stress echocardiographic protocols. PMID- 7860904 TI - Metaiodobenzylguanidine imaging in diabetes mellitus: assessment of cardiac sympathetic denervation and its relation to autonomic dysfunction and silent myocardial ischemia. AB - OBJECTIVES: This study in patients with diabetes mellitus was undertaken 1) to evaluate cardiac sympathetic innervation in diabetic patients using metaiodobenzylguanidine (MIBG) imaging; 2) to study the relation between autonomic function assessed by clinical maneuvers and abnormalities in MIBG uptake; and 3) to examine the basis for our previous observation of an association between abnormalities in autonomic nervous system dysfunction and silent myocardial ischemia. BACKGROUND: The clinical detection of autonomic dysfunction in diabetes mellitus has been linked to both abnormal perception of pain, including angina, and poor prognosis. METHODS: Uptake of MIBG was measured by dual-isotope imaging in 23 normal subjects and 65 asymptomatic diabetic patients. Silent myocardial ischemia was defined as the presence of a reversible perfusion defect in patients with ST segment depression. RESULTS: The MIBG uptake in the diabetic patients was significantly lower than that in normal subjects in the apex (67 +/- 17% vs. 82 +/- 7%, p = 0.0001), distal third (77 +/- 11% vs. 85 +/- 3%, p = 0.0001), proximal third (77 +/- 9% vs. 84 +/- 3%, p = 0.0001) and base (71 +/- 9% vs. 80 +/- 4%, p = 0.0001) of the left ventricle. Similarly, MIBG uptake was variable across different vascular territories. When MIBG uptake was corrected for perfusion abnormalities, diabetic patients had a greater MIBG uptake defect than normal subjects on visual score assessment (16 +/- 13 vs. 8 +/ 7%, p = 0.0002) and on quantitative MIBG mismatch assessment (13 +/- 15% vs. 2 +/- 2%, p = 0.0001). Diabetic patients with versus without autonomic dysfunction had more extensive MIBG uptake mismatch (17 +/- 17% vs. 4 +/- 6%, p = 0.0001). There was a greater diffuse abnormality in diabetic patients with versus without silent myocardial ischemia detected by sestamibi/MIBG uptake ratio (68 +/- 35% vs. 19 +/- 33%, p = 0.001). CONCLUSIONS: Sympathetic cardiac innervation in normal subjects is inhomogeneous. In contrast to normal subjects, diabetic patients have evidence of a significant reduction in MIBG uptake, most likely on the basis of autonomic dysfunction. Furthermore, diabetic patients with silent myocardial ischemia have evidence of a diffuse abnormality in MIBG uptake, suggesting that abnormalities in pain perception may be linked to sympathetic denervation. PMID- 7860905 TI - Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators. AB - OBJECTIVES: This study compared the effects of amlodipine, atenolol and their combination on ischemia during treadmill testing and 48-h ambulatory monitoring. BACKGROUND: It is not known whether anti-ischemic drugs exert similar effects on ischemia during ambulatory monitoring and exercise treadmill testing. METHODS: Patients with stable coronary artery disease and ischemia during treadmill testing and ambulatory monitoring were randomized to receive amlodipine (n = 51) or atenolol (n = 49). Each group underwent a counterbalanced, crossover evaluation of single drug and placebo, followed by evaluation of the combination. RESULTS: Amlodipine and the combination prolonged exercise time to 0.1-mV ST segment depression by 29% and 34%, respectively (p < 0.001) versus 3% for atenolol (p = NS). During ambulatory monitoring, the frequency of ischemic episodes decreased by 28% with amlodipine (p = 0.083 [NS]), by 57% with atenolol (p < 0.001) and by 72% with the combination (p < 0.05 vs. both single drugs; p < 0.001 vs. placebo). Suppression of ischemia during exercise testing and ambulatory monitoring was similar in patients with and without exercise-induced angina. Exercise time to angina improved by 29% with amlodipine (p < 0.01), by 16% with atenolol (p < 0.05) and by 39% with the combination (p < 0.005 vs. placebo, atenolol and amlodipine). In patients with angina, total exercise time improved by 16% with amlodipine (p < 0.001), by 4% with atenolol (p = NS) and by 19% with the combination (p < 0.05 vs. placebo and either single drug). In those patients without angina, no therapy significantly improved total exercise time. CONCLUSIONS: Ischemia during treadmill testing was more effectively suppressed by amlodipine, whereas ischemia during ambulatory monitoring was more effectively suppressed by atenolol. The combination was more effective than either single drug in both settings. PMID- 7860906 TI - Quantification of coronary artery calcium by electron beam computed tomography for determination of severity of angiographic coronary artery disease in younger patients. AB - OBJECTIVES: This study attempted to 1) evaluate five quantitative measures of coronary artery calcium and determine which best agreed with coronary artery disease severity at angiography; and 2) determine optimal quantity cutpoints to distinguish among no, mild and significant disease. BACKGROUND: Coronary artery calcium identified noninvasively by electron beam computed tomography is a sensitive marker for atherosclerosis. Quantitative assessments of calcium could distinguish among patients with no, mild and significant disease in clinical, screening and research settings. METHODS: One hundred sixty patients, 23 to 59 years old, underwent coronary angiography and electron beam computed tomography. Coronary artery calcium was defined as dense (> 130 Hounsfield units) foci > or = 2 mm2 on the tomogram. Regression and receiver operating characteristic analyses were used to evaluate five quantitative measures of calcium as predictors of the largest stenosis in the coronary arteries and to identify optimal cutpoints for distinguishing among disease categories. No disease was defined as no stenosis, mild disease as 10% to 49% diameter stenosis in one or more major branches and significant disease as > or = 50% diameter stenosis in one or more major branches. RESULTS: All measures evaluated performed well. With calcific area as the quantitative measure, the best cutpoint for discriminating between patients with and without disease was the presence of calcium: sensitivity 81%, specificity 86% and overall accuracy 83%. The best cutpoint for discriminating between patients with and without significant disease was 18 mm2: sensitivity 86%, specificity 81% and accuracy 83%. CONCLUSIONS: Because the ranges of calcium quantity overlapped across disease categories, no cutpoints would distinguish among categories with absolute certainty. However, selected cutpoints could rule out disease in most healthy subjects and identify most patients with significant disease. PMID- 7860908 TI - Flow capacity of internal mammary artery grafts: early restriction and later improvement assessed by Doppler guide wire. Comparison with saphenous vein grafts. AB - OBJECTIVES: The purpose of this study was to assess flow dynamics and flow capacities of internal mammary artery and saphenous vein grafts to the left anterior descending coronary artery. BACKGROUND: The postoperative flow capacity of internal mammary artery grafts to the left anterior descending coronary artery has been reported to be restricted compared with that of saphenous vein grafts in studies using radionuclide angiography. A recently developed Doppler guide wire has been used to analyze the flow dynamics of bypass grafts and to clarify the mechanism of this limited flow capacity. METHODS: Phasic flow velocity recordings were obtained in the midportion of the bypass graft and within the native left anterior descending artery, using a 0.018-in. (0.046-cm) 12-MHz Doppler guide wire, in 53 patients: 27 patients with an internal mammary artery graft (16 with a new graft assessed 1 month postoperatively and 11 with an old graft assessed at 1 year) and 26 patients with a saphenous vein graft (13 with a new graft assessed 1 month postoperatively and 13 with an old graft assessed at 1 year). All patients were studied at baseline rest and during hyperemia induced by intravenous infusion of dipyridamole, 0.56 mg/kg body weight, over 4 min. RESULTS: In the left anterior descending artery itself, systolic and diastolic peak velocities, the time average of the instantaneous spectral peak velocity (time-averaged peak velocity), vessel diameter and the calculated flow volume did not differ significantly among the four graft groups. The time-averaged peak velocity was significantly greater for new than for old arterial grafts or for new or old vein grafts (mean +/- SD 27 +/- 9 vs. 19 +/- 6, 11 +/- 5 and 12 +/- 6 cm/s, respectively, p < 0.01). However, because the diameter of new arterial grafts was significantly smaller than that of the other three grafts (2.4 +/- 0.1 vs. 2.9 +/- 0.2 [p < 0.05], 3.6 +/- 0.6 [p < 0.01] and 3.4 +/- 0.5 mm [p < 0.01], respectively), there was no difference in calculated flow volumes at rest (62 +/- 17 vs. 58 +/- 15, 61 +/- 18 and 58 +/- 19 ml/min, respectively, p = NS) between new arterial grafts and the other grafts. Although the maximal time-averaged peak velocity during hyperemia was significantly greater in new than in old arterial grafts or new or old vein grafts (47 +/- 17 vs. 40 +/- 7, 31 +/- 8 and 34 +/- 12 cm/s, respectively, p < 0.01), the flow reserve of new arterial grafts was significantly smaller than that of the other three groups (1.8 +/- 0.3 vs. 2.6 +/ 0.3, 2.8 +/- 0.5 and 3.0 +/- 0.6, respectively, p < 0.01) because the baseline time-averaged peak velocity of these new grafts was far greater than that of the other groups. CONCLUSIONS: Internal mammary artery graft flow early after operation is characterized by a higher rest velocity than that of vein graft flow. This high velocity maintains flow volume at baseline condition in compensation for the smaller diameter. Although flow reserve does not differ significantly between new and old vein grafts, that for internal mammary artery grafts is significantly reduced soon after bypass surgery. This restricted flow capacity improves late postoperatively because of an increase in diameter and a decrease in flow velocity from baseline levels. PMID- 7860907 TI - An explanation for discrepancy between angiographic and intravascular ultrasound measurements after percutaneous transluminal coronary angioplasty. AB - OBJECTIVES: This study attempted to determine why there is a discrepancy between angiographic and intravascular ultrasound measurements after coronary balloon angioplasty. BACKGROUND: Previous studies have shown a poor correlation between angiographic and intravascular ultrasound measurements after percutaneous coronary balloon angioplasty. METHODS: After successful balloon angioplasty, 91 lesions in 84 patients were studied by intravascular ultrasound. Plaque morphology on intravascular ultrasound was classified as demonstrating a superficial injury if there was either no fracture or only a small tear that did not extend to the media versus a deep injury defined as the presence of a plaque fracture that reached the media. Measurements of minimal lumen diameter were compared between angiography and intravascular ultrasound. RESULTS: On ultrasound imaging, a superficial injury pattern was observed in 44 lesions, whereas a deep injury was seen in 47 lesions. There were no statistical differences at baseline in patient or lesion characteristics. In the superficial injury group there was a significant correlation between angiography and intravascular ultrasound for minimal lumen diameter (r = 0.67) and lumen cross-sectional area (r = 0.69). In the deep injury group there was a poor correlation for minimal lumen diameter (r = 0.05) and lumen cross-sectional area (r = 0.28). After balloon angioplasty, the angiographic appearance showed a normal contour in 34%, the presence of dissection in 38% or a hazy appearance in 23%. On ultrasound imaging after angioplasty, the superficial injury group comprised 65% of lesions with a normal angiographic appearance and 67% of lesions with a hazy appearance, whereas 77% of lesions with an angiographic diagnosis of dissection were in the deep injury group by ultrasound (p = 0.0005). CONCLUSIONS: These observations suggest that the discrepancies between angiographic and ultrasound measurements are due to differences in plaque morphology created by balloon dilation. Superficial injuries demonstrate similar results by angiography or ultrasound, whereas a deep injury to the plaque produces a difference in measurements between angiography and ultrasound. When angiography reveals a dissection, there is a high probability that intravascular ultrasound will demonstrate a plaque fracture extending to the media. PMID- 7860909 TI - Catheter ablation of permanent junctional reciprocating tachycardia with radiofrequency current. AB - OBJECTIVES: This study evaluated accessory pathway location, its relation to retrograde P wave polarity on the surface electrocardiogram and radiofrequency ablation efficacy and safety in a large group of patients with permanent junctional reciprocating tachycardia. BACKGROUND: Permanent junctional reciprocating tachycardia is an uncommon form of reciprocating tachycardia, almost incessant from infancy and usually refractory to drug therapy. It is characterized by RP > PR interval and usually by negative P waves in leads II, III, aVF and V4 to V6. Retrograde conduction occurs through an accessory pathway with slow and decremental properties. Although this accessory pathway has been classically located in the posteroseptal zone, other locations have been recently reported. METHODS: The study included 32 patients (20 men, 12 women, mean [+/- SD] age 29 +/- 15 years) with a diagnosis of permanent junctional reciprocating tachycardia confirmed at electrophysiologic study. Seven patients had depressed left ventricular function. Radiofrequency energy was applied at the site of the earliest retrograde atrial activation during tachycardia. RESULTS: There were 33 accessory pathways. The site of the earliest retrograde atrial activation was posteroseptal in 25 patients (76%), midseptal in 4 (12%), right posterior in 1 (3%), right lateral in 1 (3%), left posterior in 1 (3%) and left lateral in 1 (3%). Thirty pathways were ablated with a right approach; in 11 patients with posteroseptal pathway the ablation was performed through the coronary sinus. Three pathways were ablated with a left approach. Positive retrograde P wave in lead I suggested that ablation could be performed from the right side; if negative, it did not exclude ablation from this approach. All the accessory pathways were successfully ablated, with a median of 3 and a mean of 5.6 +/- 5 radiofrequency applications of 70 +/- 26 s in duration. In two patients with the accessory pathway in the midseptal zone, a transient second- and third-degree atrioventricular block, respectively, was observed after ablation. At a mean follow-up of 18 +/- 12 months, 31 patients (97%) are asymptomatic without antiarrhythmic therapy (95% confidence interval [CI] 84% to 99%). Recurrences were observed in four patients (13%) (95% CI 4% to 29%), three of whom had the accessory pathway ablated successfully at a second session. All patients with depressed left ventricular function showed a marked improvement after successful ablation. CONCLUSIONS: In our experience, most of the patients with permanent junctional reciprocating tachycardia had posteroseptal pathways; all these pathways were ablated from the right side. P wave configuration may be helpful in suggesting the approach to the site of ablation. Catheter ablation using radiofrequency energy is an effective therapy for permanent junctional reciprocating tachycardia. PMID- 7860910 TI - Arrhythmogenic right ventricular cardiomyopathy in young versus adult patients: similarities and differences. AB - OBJECTIVES: This study was designed to evaluate and compare the patterns of arrhythmogenic right ventricular cardiomyopathy in young people and adults. BACKGROUND: Few data are available on this cardiomyopathy in young people because clinical and morphologic findings considered pathognomonic are normally based on observations in adults. However, a familial occurrence with a probable genetic transmission led to the study of children and to early detection of this disease, in which sudden death has been reported even in young people. METHODS: Seventeen young patients with arrhythmogenic right ventricular cardiomyopathy diagnosed at a mean age +/- SD of 14.9 +/- 4.9 years were studied. Clinical, electrocardiographic, echocardiographic, cineangiographic and biopsy findings were compared with those of 19 adult patients whose condition was diagnosed at a mean age of 38.1 +/- 13.4 years. RESULTS: Syncope occurred in 23.5% of the young patients but in none of the adults (odds ratio of familial sudden death 5.54, p = 0.1). Ventricular couplets (odds ratio 16.0, p = 0.004) and subtricuspid bulging on echocardiography (odds ratio 5.95, p = 0.036) were prevalent in the young group. Cineangiographic data in the two groups were similar, except that more hypokinetic areas were found in adults (odds ratio 4.44, p = 0.05). Morphometric analysis of biopsy sections showed a greater amount of fibrous tissue in the young patients (p = 0.04) and a prevalence of fatty tissue in the adults (odds ratio 12, p = 0.005). During an equivalent follow-up time (mean 7 years), two young patients died suddenly, and two had ventricular fibrillation in the absence of antiarrhythmic therapy. CONCLUSIONS: The pathognomonic criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy in adults are also valid for young people. Sudden or aborted death occurred frequently in young untreated patients. PMID- 7860911 TI - Aggravation of postcardioversion atrial dysfunction by sotalol. AB - OBJECTIVES: This study determined the effect of sotalol on atrial function after electrical cardioversion of atrial fibrillation. BACKGROUND: After electrical cardioversion of atrial fibrillation, the Doppler mitral A wave is often diminished, representing impaired atrial contractile function. Sotalol is an effective atrial antiarrhythmic drug with class III and beta-adrenergic blocking properties. Although the negative inotropic effect of sotalol on the ventricle is minimal in patients with normal ventricular function, it may manifest negative inotropy when ventricular function is impaired. We postulated that after cardioversion, when intrinsic atrial function is impaired, sotalol may have an adverse effect on the atrium. METHODS: Thirty-seven patients enrolled in a randomized, double-blind study of sotalol for maintenance of sinus rhythm were studied by quantitative Doppler echocardiography within 24 h of electrical cardioversion and, for those still in sinus rhythm, again at 1 month. Doppler variables (E and A wave velocities and integrals) in patients receiving sotalol were compared with those in patients receiving placebo. RESULTS: After electrical cardioversion, peak A wave velocity and A wave time-velocity integral in the 20 patients receiving placebo were reduced compared with normal values. In the 17 patients receiving sotalol (median dose 320 mg twice daily) these variables were further reduced (mean [+/- SD] peak A wave velocity 19.4 +/- 5.5 vs. 38.4 +/- 14.7 cm/s, p < 0.001 and mean A wave time-velocity integral 1.7 +/- 0.6 vs. 3.4 +/- 1.4 cm, p < 0.001, in sotalol- vs. placebo-treated patients, respectively). Early diastolic filling (E wave variables) did not differ between sotalol- and placebo-treated groups. At 1 month, five sotalol- and six placebo-treated patients remained in sinus rhythm, and A wave variables had increased for the whole group, with a greater increase in sotalol-treated patients. CONCLUSIONS: After electrical cardioversion, when atrial stunning is prominent, sotalol has a negative atrial inotropic effect. This effect may be temporary, as suggested by resolution at 1 month. Negative inotropic effects of antiarrhythmic drugs on the atrium should be considered in assessing Doppler variables of left ventricular filling. PMID- 7860912 TI - Continuous positive airway pressure increases heart rate variability in congestive heart failure. AB - OBJECTIVES: Our objective was to determine whether continuous positive airway pressure augments the low heart rate variability of congestive heart failure, a marker of poor prognosis. BACKGROUND: Nasal continuous positive airway pressure improves ventricular function in selected patients with heart failure. METHODS: In 21 sessions in 16 men (mean [+/- SE] age 56 +/- 2 years) with New York Heart Association functional class II to IV heart failure, we assessed the effects of 45 min with (n = 14) and without (as a time control, n = 7) nasal continuous positive airway pressure (10 cm of water) on heart rate variability and end expiratory lung volume. Coarse-graining spectral analysis was used to derive total spectral power (PT), its nonharmonic component (fractal power [PF]) and the low (0.0 to 0.15 Hz [PL]) and high (0.15 to 0.50 Hz [PH]) frequency components of harmonic power. Standard deviation of the RR interval, high frequency power and the PH/PT ratio were used to estimate parasympathetic activity in the time and frequency domains, and the PL/PH ratio was used to estimate cardiac sympathetic activity in the frequency domain. RESULTS: Use of continuous positive airway pressure increased end-expiratory lung volume by 445 +/- 82 ml (p < 0.01) and both time (p < 0.006) and frequency domain indexes of heart rate variability: Total spectral power (p < 0.01), nonharmonic power (p < 0.023) and low (p < 0.04) and high (p < 0.05) frequency components of harmonic power all increased. Time alone had no effect on these variables. By comparison, the PH/PT ratio increased during nasal continuous positive airway pressure (p < 0.004), whereas the PL/PH ratio was unchanged. Breathing rate remained constant in both groups. CONCLUSIONS: Short-term application of nasal continuous positive airway pressure increases heart rate variability and time and frequency domain indexes of parasympathetic activity without influencing cardiac sympathetic activity. This increase may occur reflexively, through stimulation of pulmonary mechanoreceptor afferents. PMID- 7860913 TI - Influence of preload reserve on stroke volume response to exercise in patients with left ventricular systolic dysfunction: a Doppler echocardiographic study. AB - OBJECTIVES: This study evaluated the role of preload reserve in the stroke volume response to exercise in patients with left ventricular systolic dysfunction by assessing the relation between stroke volume and late left ventricular diastolic filling during exercise. BACKGROUND: In patients with left ventricular diastolic dysfunction, the absence of left ventricular distension is the fundamental mechanism explaining the nonaugmentation of stroke volume during exercise. METHODS: In 32 patients with left ventricular systolic dysfunction and 16 healthy control subjects, mitral and aortic velocities were recorded by Doppler echocardiography at rest and during submaximal supine bicycle exercise. Stroke volume, peak early (E) and late (A) mitral velocities, A/E ratio and end diastolic filling were measured at rest and during exercise. RESULTS: Stroke volume increased significantly in control subjects but did not change in patients. Peak early mitral velocity increased significantly and to the same extent in both groups, whereas peak late mitral velocity and end-diastolic filling increased significantly in both groups but more so in control subjects; the A/E ratio increased significantly in control subjects but did not change in patients. In addition, stroke volume correlated significantly with peak late mitral velocity during exercise in patients (r = 0.72, p < 0.001). CONCLUSIONS: Compared with control subjects, patients with left ventricular systolic dysfunction exhibited limited increases in both stroke volume and late left ventricular filling during exercise. Furthermore, their stroke volume response correlated with the capacity of the left ventricle to increase late diastolic filling, that is, preload reserve. PMID- 7860914 TI - Response to isoproterenol as a prognostic indicator of evolution from hypertrophic cardiomyopathy to a phase resembling dilated cardiomyopathy. AB - OBJECTIVES: We sought to assess whether isoproterenol stress echocardiography could detect in advance in which patients hypertrophic cardiomyopathy would progress to a phase resembling dilated cardiomyopathy. BACKGROUND: In a few patients, hypertrophic cardiomyopathy has been reported to progress to a phase characterized by systolic dysfunction and left ventricular dilation, resembling dilated cardiomyopathy. METHODS: Echocardiograms were recorded before and immediately after intravenous infusion of isoproterenol (0.02 microgram/kg body weight per min) for 5 min in 18 patients with typical hypertrophic cardiomyopathy (i.e., hypertrophied, hyperdynamic and nondilated) to determine the difference in fractional shortening. The patients were categorized into those with a good response (difference in fractional shortening > 7%, 14 patients) and those with a poor response (difference < or = 7%, 4 patients). Changes in left ventricular end diastolic diameter and fractional shortening were evaluated by using serial echocardiography over an average follow-up period of 5.4 years. RESULTS: In the good response group, neither end-diastolic diameter nor fractional shortening changed significantly during the follow-up period. In the poor response group, end-diastolic diameter significantly increased from a mean +/- SD of 41 +/- 5 to 53 +/- 5 mm (p < 0.05), and fractional shortening significantly decreased from 40 +/- 12% to 29 +/- 10% (p < 0.05). All patients in the poor response group showed a substantial decrease (> or = 5%) in fractional shortening and an increase (> or = 5 mm) in end-diastolic diameter. One patient developed congestive heart failure due to systolic dysfunction during the observation period. CONCLUSIONS: The present study confirmed that impaired responses to isoproterenol infusion are related to future deterioration of left ventricular performance in patients with typical hypertrophic cardiomyopathy. PMID- 7860915 TI - Exercise-induced mitral regurgitation is a predictor of morbid events in subjects with mitral valve prolapse. AB - OBJECTIVES: This study attempted to determine whether a subset of patients with mitral valve prolapse and no mitral regurgitation at rest will develop mitral regurgitation during exercise and have a higher than anticipated risk of morbid cardiovascular events. BACKGROUND: Mitral regurgitation in patients with mitral valve prolapse identifies a subset of patients at higher risk for morbid events. However, mitral regurgitation in patients with mitral valve prolapse may be intermittent and could go unrecognized. A provocative test to unmask mitral regurgitation in these patients would be useful. METHODS: Ninety-four adult patients with mitral valve prolapse and no mitral regurgitation at rest were studied during supine bicycle ergometry using color flow Doppler echocardiography in the apical four-chamber and long-axis views. Patients were prospectively followed up for morbid events. RESULTS: Thirty (32%) of 94 patients had exercise induced mitral regurgitation. Prospective follow-up (mean 38 months) showed more morbid events in the group with than without mitral regurgitation and included, respectively, syncope (43% vs. 5%, p < 0.0001), congestive heart failure (17% vs. 0%, p < 0.005) and progressive mitral regurgitation requiring mitral valve replacement surgery (10% vs. 0%, p < 0.05). Cerebral embolic events, endocarditis or sudden death were rare and not different between groups. CONCLUSIONS: In patients with mitral valve prolapse without mitral regurgitation at rest, exercise provokes mitral regurgitation in 32% of patients and predicts a higher risk for morbid events. PMID- 7860916 TI - Exercise-induced regurgitation in mitral valve prolapse: is it a new disease? PMID- 7860917 TI - Effective mitral regurgitant orifice area: clinical use and pitfalls of the proximal isovelocity surface area method. AB - OBJECTIVES: We attempted to determine the accuracy and pitfalls of calculating the mitral regurgitant orifice area with the proximal isovelocity surface area method in a clinical series that included patients with valvular prolapse and eccentric jets. BACKGROUND: The effective regurgitant orifice area, a measure of lesion severity of mitral regurgitation, can be calculated by the proximal isovelocity surface area method, the accuracy and pitfalls of which have not been established. METHODS: In 119 consecutive patients with isolated mitral regurgitation, effective regurgitant orifice area was measured by the proximal isovelocity surface area method and compared with measurements simultaneously obtained by quantitative Doppler and quantitative two-dimensional echocardiography. RESULTS: The effective mitral regurgitant orifice area measured by the proximal isovelocity surface area method tended to be overestimated compared with that measured by quantitative Doppler and quantitative two dimensional echocardiography (38 +/- 39 vs. 36 +/- 33 mm2 [p = 0.09] and 34 +/- 32 mm2 [p = 0.02], respectively). Overestimation was limited to patients with prolapse (61 +/- 43 vs. 56 +/- 35 mm2 [p = 0.05] and 54 +/- 34 mm2 [p = 0.014]) and was restricted to patients with nonoptimal flow convergence (n = 7; 137 +/- 35 vs. 84 +/- 34 mm2 [p = 0.002] and 79 +/- 33 mm2 [p = 0.002]). In patients with optimal flow convergence (n = 112), excellent correlations with both reference methods were obtained (r = 0.97, SEE 6 mm2 and r = 0.97, SEE 7 mm2, p < 0.0001). CONCLUSIONS: In calculating the mitral effective regurgitant orifice area with the proximal isovelocity surface area method, the observed pitfall (overestimation due to nonoptimal flow convergence) is rare. Otherwise, the method is reliable and can be used clinically in large numbers of patients. PMID- 7860918 TI - Cardiac index quantification by Doppler ultrasound in patients without left ventricular outflow tract abnormalities. AB - OBJECTIVES: We attempted to ascertain whether cardiac index can be directly estimated from Doppler mean velocity. BACKGROUND: Although diverse Doppler echocardiographic methods have been described for cardiac output quantification, they are not widely used in clinical practice. Cross-sectional area measurement has been identified as the main source of error in flow volume quantification. METHODS: A three-phase study by Doppler echocardiography was conducted in 306 patients. In phase I, the normal mean velocity ratio of the left and right ventricular outflow tracts was established in 170 normal subjects. In phase II, cardiac index, calculated as the product of aortic annular area index by mean velocity (conventional method), and mean velocity determined in the left ventricular outflow tract and ascending aorta by pulsed and continuous wave Doppler, respectively, were correlated with thermodilution cardiac index in 66 patients. In phase III, the accuracy of the regression equations obtained was prospectively assessed in an additional 70 patients. RESULTS: The normal left/right ventricular outflow tract mean velocity ratio by pulsed wave Doppler was 1.1 +/- 0.1. Cardiac index (CI) calculated by the conventional method and thermodilution (TD) showed acceptable correlation (r = 0.90, CITD = 1.20 CIPWD + 357; r = 0.86, CITD = 0.90 CICWD + 262) for pulsed (PWD) and continuous wave (CWD) Doppler, respectively, but with systematic underestimation (-28 +/- 13%, p < 0.01) by pulsed wave Doppler. Mean velocity (MV) showed excellent correlation with the thermodilution cardiac index (r = 0.97, CITD = 172 MVPWD - 172; r = 0.93, CITD = 129 MVCWD - 255). When these regression equations were prospectively applied, better agreement with the thermodilution cardiac index was obtained by pulsed wave Doppler directly from mean velocity (SD 240 ml/min per m2) than when aortic annular area was considered in the calculation (SD 428 ml/min per m2). Similar results were obtained by continuous wave Doppler (SD 433 vs. 599 ml/min per m2) but with less accuracy. CONCLUSIONS: Left ventricular outflow tract mean velocity determined by pulsed wave Doppler permits easy, accurate cardiac index quantification in the absence of left ventricular outflow abnormalities. The simplicity of this method enhances its clinical applicability in noninvasive monitoring of cardiac index. PMID- 7860919 TI - New method for evaluating left ventricular wall motion by color-coded tissue Doppler imaging: in vitro and in vivo studies. AB - OBJECTIVES: The aim of this study was to examine the accuracy and validity of a newly developed tissue Doppler imaging system in in vitro and in vivo studies. BACKGROUND: Because quantitative measurement of wall motion velocity in real time is still difficult by conventional echocardiography, we developed a new system for evaluating ventricular wall motion by analyzing Doppler signals from cardiac tissue. METHODS: We used a modified Doppler color imaging system, omitting the high pass filter to allow Doppler signals from cardiac tissue to enter the auto correlator. Ultrasound carrier and pulse repetition frequencies were 3.75 MHz and 3.0 to 6.0 kHz, respectively. Under these conditions, the lowest measurable velocity was 0.2 cm/s. RESULTS: In the rotating sponge model, the measured velocity correlated well with the actual velocity (y = 0.97x + 2.17, r = 0.99). In clinical settings, the mid-ejection mean velocity at either endocardial or epicardial sites of the left ventricular posterior wall measured by M-mode tissue Doppler imaging correlated well with that measured by conventional M-mode echocardiography (y = 0.94x + 0.64, r = 0.99). During systole, in healthy subjects, the anterior left ventricular wall was color-coded blue and the posterior wall was color-coded red, whereas the akinetic regions associated with myocardial infarction showed no color throughout the cardiac cycle. The ventricular posterior wall excursion velocity, defined as the difference between velocities at the endocardial and epicardial sites, was significantly slower in patients with dilated cardiomyopathy (0.4 +/- 0.3 cm/s) than in normal subjects (2.0 +/- 0.6 cm/s). CONCLUSIONS: These results indicate that the present system accurately represents tissue velocity and can create two-dimensional color images that facilitate visual assessment of ventricular wall motion. PMID- 7860920 TI - Rational approach to use of heparin during cardiac catheterization in children. AB - OBJECTIVES: We sought to determine an anticoagulation protocol for use during cardiac catheterization in children. BACKGROUND: There are few data to indicate which dose of heparin represents adequate anticoagulation or how best to monitor its efficacy. In this study, adequate anticoagulation was defined as the amount of heparin needed to prevent a significant increase in serum fibrinopeptide A, a sensitive marker for thrombin activity. The degree of heparinization was estimated by the activated clotting time. METHODS: Thirty-six children (1 month to 19.5 years old) with congenital heart disease underwent diagnostic cardiac catheterization; 13 of these 36 patients had an additional interventional procedure. Sheaths and catheters were flushed with heparinized saline (1 IU/ml); during the procedure, 33 of the 36 patients received either a 50- or a 100-IU/kg heparin bolus. Paired fibrinopeptide A and activated clotting time samples were obtained throughout each procedure. RESULTS: Increasing the activated clotting time with heparin resulted in a dose-related decrease in fibrinopeptide A levels. A single heparin bolus of either 50 or 100 IU/kg elevated the activated clotting time above baseline level (209 +/- 52 s after 50 IU/kg, 270 +/- 57 s after 100 IU/kg vs. 133 +/- 20 s at baseline [p < 0.0001]) and reduced fibrinopeptide A levels below baseline (7.9 +/- 14 ng/ml after 50 IU/kg, 4.8 +/- 3.7 ng/ml after 100 IU/kg vs. 38 +/- 59 ng/ml at baseline [p < 0.0001]). Heparin flush alone did not increase the activated clotting time above baseline and failed to suppress an increase in fibrinopeptide A levels. There were no differences in activated clotting time and fibrinopeptide A values between patients undergoing diagnostic or interventional procedures. CONCLUSIONS: Administration of a heparin bolus to maintain an activated clotting time > 200 s prevented a significant increase in thrombin activity. Heparin flush alone did not provide adequate anticoagulation. Patients undergoing an interventional procedure did not require more heparin than that needed for a diagnostic procedure. PMID- 7860921 TI - Balloon angioplasty of native coarctation of the aorta: midterm follow-up and prognostic factors. AB - OBJECTIVES, This retrospective analysis was designed to examine the intermediate and long-term effects of balloon angioplasty for native coarctation of the aorta and to determine whether any factors are predictive of outcome. BACKGROUND: Balloon angioplasty for native coarctation of the aorta is controversial. Concerns exist over lack of long-term follow-up and possible formation of aneurysms. The role of transverse arch and isthmus hypoplasia after balloon dilation is unknown. METHODS: Included in the study were all patients 3 days to 29 years old (mean age 4.6 years) referred for possible balloon dilation to the pediatric cardiac catheterization laboratory with evidence of a discrete coarctation of the aorta. The hemodynamic data, angiograms and clinical records of 102 patients were examined, with follow-up data from 2 to 117 months (median 36.2) available in 92 patients. RESULTS: Immediate success with balloon angioplasty was achieved in 93 (91.2%) of the 102 patients. Seventy-one patients (77.2%) with intermediate follow-up data (range 12 to 117 months) available are asymptomatic and normotensive, with insignificant arm to leg blood pressure gradients (< or = 20 mm Hg). Twenty-one patients (22.8%) with an initial successful result developed an increase in gradient 2 at 86 months after angioplasty, requiring reintervention in 18. Follow-up > 72 months is available in 17 patients, 16 of whom are normotensive and have not required additional intervention. No additional intervention was needed in 88.4% of older children and infants > 7 months old. Ten of the 13 surviving neonates who initially had a successful dilation required reangioplasty or operation 14 days to 10 months (median 4.6 months) after angioplasty. Transverse arch hypoplasia had minimal effect on follow-up blood pressure gradient, whereas isthmic hypoplasia was associated with reintervention in 50%. A small aneurysm was noted in 2 (1.9%) of 102 patients. CONCLUSIONS: Balloon angioplasty of native aortic coarctation is effective in infants and older children. In neonates, balloon angioplasty provides effective palliation only. Aneurysm formation is rare; however, lifetime follow-up is warranted. PMID- 7860922 TI - Pulmonary/systemic flow ratio in children after cavopulmonary anastomosis. AB - OBJECTIVES: This study attempted to provide a formula for calculation of the pulmonary/systemic flow ratio in children after bidirectional cavopulmonary anastomosis. BACKGROUND: With the bidirectional cavopulmonary anastomosis, only the superior vena cava blood is oxygenated by the lungs. The inferior vena cava flow recirculates into the systemic circulation. The ratio of these flows will determine systemic arterial saturation. METHODS: According to the Fick principle, 1) Systemic cardiac output (liters/min) = Pulmonary venous flow + Inferior vena cava flow; 2) Systemic blood oxygen transport (ml/min) = Pulmonary venous blood oxygen transport + Inferior vena cava blood oxygen transport. By substituting the first equation into the second, Pulmonary/systemic flow ratio = (Systemic saturation - Inferior vena cava saturation)/(Pulmonary venous saturation - Inferior vena cava saturation). RESULTS: We applied the third formula to data obtained from 34 catheterizations in 29 patients after bidirectional cavopulmonary anastomosis. Mean [+/- SD] age at operation was 1.70 +/- 1.43 years, and mean age at catheterization was 2.95 +/- 1.65 years. The pulmonary/systemic flow ratio calculated for all 29 patients was 0.58 +/- 0.09. Of 17 patients with aortography, 10 had systemic to pulmonary collateral vessels. Patients with collateral vessels had a significantly higher pulmonary/systemic flow ratio (0.61 +/- 0.07 vs. 0.53 +/- 0.07, respectively, p < 0.02) and systemic saturation (88 +/- 4% vs. 82 +/- 4%, respectively, p < 0.002) than those without collateral vessels. The pulmonary/systemic flow ratio in those patients with no collateral vessels was similar to the previously reported echocardiographically derived superior vena cava/systemic flow ratio in normal children. CONCLUSIONS: The pulmonary/systemic flow ratio after bidirectional cavopulmonary anastomosis can be calculated. Pulmonary blood flow in these patients determines systemic saturation and accounts for the majority of venous return in young children. PMID- 7860923 TI - In utero pulmonary artery and aortic growth and potential for progression of pulmonary outflow tract obstruction in tetralogy of Fallot. AB - OBJECTIVES: This study was designed to define patterns of pulmonary artery and aortic growth in fetuses with tetralogy of Fallot and to determine the potential for in utero progression of right ventricular outflow tract obstruction. BACKGROUND: Despite an abundance of reports documenting the prenatal diagnosis of tetralogy of Fallot, there is little information about its course in utero. METHODS: Pulmonary artery and ascending aortic diameters were measured from prenatal and postnatal echocardiograms of 16 fetuses with tetralogy of Fallot, initially studied at 23.6 +/- 6.0 (mean +/- SD) weeks of gestation. Fetuses were classified retrospectively as having mild and severe tetralogy of Fallot according to whether the pulmonary artery circulation was (severe, n = 5) or was not (mild, n = 11) ductus arteriosus dependent at birth. RESULTS: Initial main pulmonary artery diameter was small for gestational age in 9 fetuses, large in 2 and normal in 5 compared with data from 57 gestational age-adjusted normal fetal studies; it was significantly smaller in the group with severe tetralogy of Fallot (p = 0.05). The initial main pulmonary artery/aortic diameter ratio was also smaller for the group with severe tetralogy of Fallot (0.50 +/- 0.15 vs. 0.73 +/- 0.14 in the group with mild tetralogy of Fallot, p = 0.01). Initial aortic and branch pulmonary artery diameters tended to be normal or near normal for age. In eight fetuses serially studied, main and branch pulmonary artery growth was normal or reduced during prenatal follow-up. Pulmonary artery growth was most reduced in two fetuses in the group with severe tetralogy of Fallot, resulting in pulmonary artery hypoplasia at birth. Two fetuses with valvular pulmonary atresia at birth had previously shown anterograde pulmonary outflow in midgestation, suggesting progression of pulmonary outflow obstruction. CONCLUSIONS: The postnatal spectrum of pulmonary artery size in tetralogy of Fallot can be attributed to variable patterns of growth in utero. Main pulmonary artery size, main pulmonary artery/aortic diameter ratio and pattern of pulmonary artery growth may be predictive of the severity of postnatal pulmonary outflow obstruction. Pulmonary atresia can develop in utero in some fetuses with tetralogy of Fallot. PMID- 7860924 TI - Electrocardiographic indexes of dispersion of ventricular repolarization: an isolated heart validation study. AB - OBJECTIVES: This study tested the correlation of QT and JT dispersion and other potentially useful electrocardiographic (ECG) indexes with dispersion of repolarization and recovery time. BACKGROUND: Dispersion of ventricular repolarization is currently being assessed noninvasively from the surface ECG by means of QT and JT dispersion, although their correlation with dispersion of repolarization as measured directly from the myocardium is not well established. METHODS: Multiple monophasic action potentials were recorded simultaneously with a 12-lead ECG from isolated Langendorff-perfused rabbit hearts. The QT and JT dispersion was compared with the dispersion of monophasic action potential duration at 90% repolarization (APD90) and with dispersion of recovery time. As new ECG indexes, total T wave area, T wave area after the peak (late T wave area) and T peak to T end interval were also tested. RESULTS: The QT and JT dispersion showed a significant correlation with the dispersion of APD90 and the dispersion of recovery time (r values between 0.58 and 0.64, respectively, p < 0.001). However, total T wave area showed better correlation, respectively, with dispersion of APD90 and recovery time (r = 0.79 and r = 0.82, p < 0.0001), as did late T wave area (r = 0.81 and r = 0.81, p < 0.0001) and T peak to T end interval (r = 0.81 and r = 0.82, p < 0.0001). CONCLUSIONS: The JT and QT dispersion correlate significantly with dispersion of APD90 and recovery time. The ECG assessment of dispersion of repolarization can be improved by three new ECG dispersion indexes: T peak to T end interval, total T wave area and late T wave area. These new indexes should be tested clinically. PMID- 7860925 TI - Recombinant lys-plasminogen, but not glu-plasminogen, improves recombinant tissue type plasminogen activator-induced coronary thrombolysis in dogs. AB - OBJECTIVES: This study examined the modification of recombinant tissue-type plasminogen activator (rt-PA)-induced thrombolysis by recombinant lys plasminogen. BACKGROUND: Recombinant tissue-type plasminogen activator restores flow in the thrombosed coronary artery, but the artery often reoccludes. The rt PA-induced thrombolysis is a result of activation of plasminogen bound to fibrin in the thrombus and results in generation of the fibrinolytic enzyme plasmin. Small amounts of lys-plasminogen are formed when rt-PA is used. Lys-plasminogen binds to fibrin with a 10-fold greater affinity than the predominant native glu plasminogen, leading to a loose fibrin structure. METHODS: Dogs with electrically induced occlusive intracoronary thrombus were treated with saline solution (n = 9), glu-plasminogen (2 mg/kg body weight, n = 5) or lys-plasminogen (2 mg/kg, n = 5), followed by infusion of rt-PA (1 mg/kg over 20 min) 10 min later. RESULTS: Reperfusion rates were similar in all groups of dogs, but the time to reflow was lowest in dogs given lys-plasminogen compared with those given saline solution or glu-plasminogen before rt-PA (mean [+/- SE] 14 +/- 2 vs. 22 +/- 2 and 23 +/- 3 min, respectively, p < 0.05). None of the reperfused coronary arteries reoccluded in the lys-plasminogen plus rt-PA group, whereas 75% reoccluded in dogs given saline solution plus rt-PA, and 50% reoccluded in those given glu-plasminogen plus rt-PA. Accordingly, duration of reflow was greater in the lys-plasminogen plus rt-PA group (> 120 vs. 39 +/- 7 and 82 +/- 21 min, respectively, p < 0.05). Plasminogen activator inhibitor-1 activity decreased during rt-PA infusion and thereafter increased in all dogs, but less so in dogs given lys-plasminogen (p < 0.05 vs. those given saline solution before rt-PA). CONCLUSIONS: Treatment with recombinant lys-plasminogen before rt-PA reduces time to reflow and sustains reflow after thrombolysis, whereas glu-plasminogen has no such effect. PMID- 7860926 TI - Selective downregulation of rat cardiac beta 1-adrenoceptors by cyclosporine A: prevention by diltiazem or angiotensin-converting enzyme inhibitors. AB - OBJECTIVES: This study attempted to determine whether long-term treatment with cyclosporine A in rats affects cardiac beta 1-adrenoceptors and whether this can be prevented by angiotensin-converting enzyme inhibitors or calcium-entry blocking agents. BACKGROUND: In the transplanted human heart the density of beta 1-adrenoceptors decreases with time after transplantation, whereas that of beta 2 adrenoceptors does not. Because heart transplant recipients are treated with cyclosporine A, we studied whether administration of cyclosporine A in rats might cause this beta 1-adrenoceptor downregulation. METHODS: We performed two studies. First, we treated groups of 10 male normotensive Wistar rats orally with 30 mg/kg body weight per day of cyclosporine A, 10 mg/kg per day of enalapril and 60 mg/kg per day of diltiazem, alone or in combination, for 6 weeks each. Second, we treated groups of 15 male normotensive Wistar rats orally with 15 mg/kg per day of cyclosporine A and 10 mg/kg per day of lisinopril, alone or in combination, for 6 weeks each. At the end of each treatment regimen, cardiac beta-adrenoceptor density and subtype distribution were assessed by (-)-[125I]iodocyanopindolol binding. RESULTS: Both doses of cyclosporine A caused a significant decrease in cardiac beta 1-adrenoceptor density without affecting beta 2-adrenoceptor density. Although diltiazem and the angiotensin-converting enzyme inhibitors alone did not affect cardiac beta-adrenoceptors, they prevented the cyclosporine A-induced downregulation of beta 1-adrenoceptors. CONCLUSIONS: In normotensive Wistar rats, cyclosporine A causes a significant decrease in cardiac beta 1 adrenoceptors without affecting beta 2-adrenoceptors. This can be prevented by diltiazem or angiotensin-converting enzyme inhibitors. In heart transplant recipients, who undergo long-term treatment with cyclosporine A, there is a very similar beta 1-adrenoceptor down-regulation with time after transplantation. Thus, administration of cyclosporine A may cause these beta-adrenoceptor subtype alterations. PMID- 7860927 TI - Effects of long-term therapy with enalapril on severity of functional mitral regurgitation in dogs with moderate heart failure. AB - OBJECTIVES: This study examined the effects of early long-term monotherapy with enalapril on the severity of functional mitral regurgitation in dogs with moderate heart failure. BACKGROUND: Functional mitral regurgitation often develops in patients with heart failure and, depending on its severity, can have a marked adverse impact on the stroke output of the failing left ventricle and contribute to progressive deterioration of the heart failure state. METHODS: Left ventricular dysfunction (ejection fraction 30% to 40%) was produced in 14 dogs by multiple sequential intracoronary microembolizations. Dogs were randomized to 3 months of therapy with enalapril (10 mg twice daily, n = 7) or no therapy at all (control, n = 7). The severity of functional mitral regurgitation was quantified by Doppler color flow mapping in seven control and six enalapril-treated dogs. Mitral annular diameter was assessed by echocardiography and left ventricular volumes and shape by ventriculography. Measurements were made before initiation and after completion of therapy. RESULTS: In control dogs, the severity of mitral regurgitation increased during the follow-up period ([mean +/- SEM] 14 +/- 4 vs. 23 +/- 4%, p < 0.001) and was associated with increased left ventricular end systolic and end-diastolic volumes. In contrast, the severity of regurgitation was not significantly changed in dogs treated with enalapril (18 +/- 3 vs. 16 +/- 6%, p < 0.59) and was associated with preservation of left ventricular volumes. CONCLUSIONS: In dogs with moderate heart failure, early long-term therapy with enalapril prevents progressive worsening of functional mitral regurgitation. This beneficial effect is most likely achieved by prevention of progressive left ventricular dilation. PMID- 7860928 TI - Differential effects of protamine sulfate on myocyte contractile function with left ventricular failure. AB - OBJECTIVES: This project tested two fundamental hypotheses: 1) Protamine sulfate has a direct and negative effect on myocyte contractile processes; 2) the negative effects of protamine on myocyte contractility will be enhanced in the setting of chronic left ventricular dysfunction. BACKGROUND: An increasing number of patients undergoing cardiac and vascular surgical procedures have underlying chronic left ventricular dysfunction. Protamine sulfate is commonly required during these surgical procedures but has been associated with left ventricular dysfunction. However, it is not known whether protamine may have a direct and selective effect on myocyte contractility in the setting of chronic left ventricular dysfunction. METHODS: This study examined the direct effects of protamine on isolated myocyte contractile function in 10 control pigs and 10 pigs with dilated cardiomyopathy induced by supraventricular tachycardia (rapid atrial pacing at 240 beats/min for 3 weeks). Myocyte contractile function was measured by videomicroscopy at baseline and with 10, 20, 40 or 80 micrograms/ml of protamine. In a second series of experiments, myocytes were preincubated with protamine and then stimulated with the beta-adrenergic agonist isoproterenol (25 nmol/liter). RESULTS: In the presence of 20 micrograms/ml of protamine, myocyte contractile function was unaffected in the control group but decreased by 40% from baseline values in the supraventricular tachycardia group. With 10 micrograms/ml of protamine, myocyte beta-adrenergic responsiveness was reduced by 25% in the supraventricular tachycardia group with no change in the control group. In the presence of 40 and 80 micrograms/ml of protamine, myocyte contractile function decreased in both groups. However, 40 micrograms/ml of protamine caused a more pronounced decline in myocyte function and beta adrenergic responsiveness in the supraventricular tachycardia group. CONCLUSIONS: An increased sensitivity to the depressive effects of protamine on myocyte contractile function and beta-adrenergic responsiveness occurred in this model of chronic left ventricular dysfunction. These results suggest that patients with underlying cardiac disease may have an increased susceptibility to a sudden compromise of left ventricular contractile performance after protamine administration. PMID- 7860929 TI - A chimeric IgG4 monoclonal antibody directed against CD18 reduces infarct size in a primate model of myocardial ischemia and reperfusion. AB - OBJECTIVES: This study attempted to determine whether neutrophil sequestration in reperfused myocardium can be inhibited and infarct size reduced by treatment with a chimeric, monoclonal IgG4 antibody (CLB54) directed against CD18 in a primate model of acute myocardial ischemia and reperfusion. BACKGROUND: Reperfusion injury, in part mediated by neutrophils, may limit the potential benefit of reestablishing infarct-related artery patency in patients with acute myocardial infarction. METHODS: Nineteen closed-chest baboons (10 control, 9 treated with CLB54) had the left anterior descending coronary artery occluded for 90 min, followed by 4 h of reflow. CLB54 (mean [+/- SD] 11 +/- 2 mg/kg body weight) or saline solution was administered intravenously 20 min before reflow. Coronary flow was determined using radiolabeled microspheres, infarct size by triphenyltetrazolium chloride staining, global and regional ventricular function by contrast ventriculography and neutrophil accumulation by a myeloperoxidase assay. RESULTS: Risk region size was the same in both groups. CLB54 treatment reduced infarct size expressed as a percent of the risk region from 41 +/- 20% in the saline-treated group to 19 +/- 17% in the CLB54-treated group (p < 0.02). This was associated with diminished myeloperoxidase activity and greater postreperfusion coronary flow in the risk region in CLB54-treated than in control baboons. Ejection fraction declined to the same extent in both groups, whereas anterior wall regional cord shortening was better preserved in CLB54-treated baboons. CONCLUSIONS: Inhibition of neutrophil sequestration with CLB54 administered before reperfusion reduces infarct size, preserves ischemic zone microvascular perfusion and minimizes the decline of regional wall motion. PMID- 7860930 TI - Effects of exercise training in patients with congestive heart failure: a critical review. AB - Congestive heart failure is a potentially debilitating disorder that affects a significant number of patients. The age-adjusted death rate has doubled over the past decade. Patients live an average of 4 to 5 years, and nearly all suffer from fatigue and breathlessness, which limits exercise capacity and produces a poor quality of life. Patients have usually been advised to avoid exercise because of concerns that they would experience a further decline in cardiac function. However, it has been demonstrated that exercise capacity is not related to the degree of left ventricular systolic dysfunction. This has led to the suggestion that peripheral changes in skeletal muscle and blood supply may play a major role in determining the exercise capacity of patients with congestive heart failure. Studies have demonstrated abnormalities of skeletal muscle blood flow, metabolism and structure, all of which are consistent with the impaired performance observed in these patients. Although the effects of exercise training have been examined in only a relatively few number of patients, the results have been promising. Exercise training has been found to improve exercise capacity and reduce symptoms. However, to our knowledge no data exist as to the impact of exercise training on left ventricular function, hospital stay or mortality in this population. Even though the early results are promising, they require confirmation of feasibility, clinical benefit and safety in larger, long-term randomized trials. It should be determined whether training has a long-term beneficial impact on measures more closely related to daily activities and quality of life. Ultimately, it would be important to determine whether training has an impact on mortality and morbidity. PMID- 7860931 TI - "It's a small world after all". PMID- 7860932 TI - The assault on specialty medicine. PMID- 7860933 TI - American College of Cardiology, American College of Radiology and industry develop standard for digital transfer of angiographic images. ACC/ACR/NEMA Ad Hoc Group. PMID- 7860934 TI - Hemochron versus HemoTec activated coagulation time target values during percutaneous transluminal coronary angioplasty. PMID- 7860935 TI - Congestive heart failure and sodium dichloroacetate. PMID- 7860936 TI - Food guide pyramid stimulates debate. PMID- 7860937 TI - Food guide pyramid stimulates debate. PMID- 7860938 TI - Food guide pyramid stimulates debate. PMID- 7860939 TI - Nutrition & health campaign for all women. PMID- 7860940 TI - States test health care reform through Medicaid waivers. PMID- 7860941 TI - Helping Americans eat right: developing practical and actionable public nutrition education messages based on the ADA Survey of American Dietary Habits. PMID- 7860942 TI - Drug-nutrient interactions in three long-term-care facilities. AB - OBJECTIVE: To assess the risk of drug-nutrient interactions (DNIs) in three long term-care facilities. DESIGN: Retrospective audit of charts. SETTING: Three long term-care facilities in central New York State. SUBJECTS: Fifty-three patients selected randomly from each facility. MEASUREMENT: Data were collected from the medical record of each patient for a period of 6 months. A computerized algorithm was used to assess the risk for DNIs. Mean drug use, most frequently consumed drugs, incidence of potential DNIs, and the most commonly observed potential DNIs are reported. RESULTS: In facilities A, B, and C, respectively, patients consumed a mean of 4.86, 4.04, and 5.27 drugs per patient per month and were at risk for a mean of 1.43, 2.69, and 1.43 potential DNIs per patient per month. The most commonly observed potential DNIs were gastrointestinal interactions affecting drug bioavailability and interactions affecting electrolyte status. CONCLUSIONS: Patients in long-term-care facilities, who are primarily elderly and chronically ill and who consume multiple medications, are at notable risk for certain DNIs. Efforts need to be made to ensure appropriate pharmacologic and nutrition therapies as well as adequate and timely monitoring of patients in these facilities. Dietitians can play an important role in training other health professionals and in designing policies to prevent DNIs. PMID- 7860943 TI - Barriers to the adoption of reduced-fat diets in a UK population. AB - OBJECTIVE: To assess perceived and actual barriers to dietary fat reduction. DESIGN: A 20-week intervention study was carried out to investigate the problems encountered by persons attempting to reduce their fat intake. SUBJECTS: Seventy subjects initially consuming moderately high-fat diets were recruited from the local area by newspaper advertisement. Sixty-one completed the study. INTERVENTION: Subjects were randomized into either a control or an experimental group. Subjects in the experimental group (n = 45) received instruction on reducing their intake of fat using current dietary recommendations. All subjects initially completed a questionnaire to assess their beliefs and attitudes regarding selected dietary changes, and the experimental group also completed a similar questionnaire at intervals during the study. Weighed diet records were completed by all subjects throughout the study. STATISTICAL ANALYSIS: Repeated measures analysis of variance was used to examine changes in nutrient intake. Univariate analysis of variance was used to examine differences in barriers encountered by most and least successful fat reducers. RESULTS: Perceived barriers reflected actual problems encountered. One of the most consistently reported problems was that of reduction in taste quality of the diet. Other problems included an increase in cost, decrease in convenience, lack of family support for certain changes, and an inability to judge the fat content of diets. APPLICATIONS/CONCLUSIONS: Strategies aimed at improving the taste of low-fat diets, increasing awareness of fat intake, and increasing family support may be most effective in promoting greater adherence to dietary guidelines intended to achieve reductions in fat consumption. PMID- 7860944 TI - Influences on breast-feeding by lower-income women: an incentive-based, partner supported educational program. AB - OBJECTIVE: To determine the effects of a partner-supported, incentive-based educational program on rates and duration of breast-feeding among low-income women. DESIGN: Women who expressed a willingness to participate in the breast feeding educational program were randomly assigned to one of two groups: an intervention group and a control group who received usual breast-feeding education. SETTING: Clinics of the Special Supplemental Food Program for Women, Infants, and Children in Flagstaff, Ariz. SUBJECTS: Sixty-eight primiparous pregnant women with expected due dates between May 1992 and December 1992 were willing to participate in the study. Of these, 34 were randomly assigned to the intervention group and 34 to the control group. Approximately 81% of the women completed the study: 29 in the control group and 26 in the intervention group. INTERVENTION: The intervention consisted of special incentives (prizes) for women and their partners to participate in a breast-feeding class for expectant couples and an educational series on childbirth. Women were also encouraged to use a breast-feeding support program in which peers serve as role models. MAIN OUTCOME MEASURES: The primary outcome measure was infant feeding method. Data were collected from mothers in both groups at the time of discharge from the hospital and at 2 weeks, 6 weeks, and 3 months postpartum. STATISTICAL ANALYSES PERFORMED: Binomial proportional analyses of the feeding data were performed. RESULTS: Women in the intervention group reported a higher percentage of breast-feeding at all measurement times. APPLICATIONS: These findings suggest that incentives, such as donated prizes, can be used to attract primiparous women from lower socioeconomic groups, along with their partners, to participate in educational interventions designed to promote breast-feeding. Participation by couples in breast-feeding promotion activities can dramatically increase the rate and duration of breast feeding. PMID- 7860945 TI - Vitamin and mineral intakes of Anglo-American and Mexican-American preschoolers. AB - OBJECTIVE: To assess vitamin and mineral intakes of Anglo-American and Mexican American preschoolers. DESIGN: By use of interview and observation methods, acquire food intake data, calculate total nutrient intake, and compare selected nutrients to the Recommended Dietary Allowances (RDAs) for ethnic and gender groups. SUBJECTS: Low- to middle-income parents and their preschool children (N = 351) recruited from preschools in San Diego, Calif, consented to participate in the Study of Children's Activity and Nutrition conducted by researchers at the University of California, San Diego. MAIN OUTCOME MEASURES: Data regarding 15 nutrients were summarized based on the average of two food intake records for each preschooler. STATISTICAL ANALYSES PERFORMED: Means and standard deviations were used to describe micronutrient intakes for ethnic and gender groups; analyses of variance and t tests were performed to determine ethnic and gender differences. RESULTS: Boys and Anglo-Americans had higher total nutrient intakes than girls and Mexican-Americans, respectively. Mexican-Americans had higher nutrient intakes per energy intake, which indicates a micronutrient-dense diet. When each nutrient was considered by the two thirds of the RDA criterion (66% of the RDA means adequate intake), the nutrients most likely to be inadequate were iron, zinc, vitamin D, vitamin C, and niacin. Mexican-American girls had significantly lower calcium intakes than the other gender and ethnic groups. APPLICATION: Parents and day care providers must ensure that preschoolers, especially girls and Mexican-Americans, eat nutrient-rich foods in adequate quantities that will achieve the recommended intakes. PMID- 7860946 TI - Development and reproducibility of a food frequency questionnaire to assess diets of older children and adolescents. AB - OBJECTIVE: To develop a self-administered food frequency questionnaire for older children and adolescents and to demonstrate reproducibility over a 1-year period. DESIGN: The youth/adolescent questionnaire (YAQ) was based on the validated Nurses' Health Study food frequency questionnaire and was developed to reflect the eating habits of this age group. SUBJECTS: The multiethnic sample consisted of 179 youths (ages 9 to 18 years) who completed the questionnaire twice, 1 year apart. STATISTICAL ANALYSIS: Pearson correlation coefficients were calculated on nutrient data adjusted in relation to energy intake and on unadjusted food data. RESULTS: Reproducibility for nutrients ranged from .26 for protein and iron to .58 for calcium, and for foods it ranged from .39 for meats to .57 for soda. Mean reproducibility was higher among girls than boys for energy and nutrients and for foods; no consistent pattern was observed for age. CONCLUSION: A self administered food frequency questionnaire has a reasonable ability to assess the eating habits of older children and adolescents over time. PMID- 7860947 TI - Problems encountered in meeting the Recommended Dietary Allowances for menus designed according to the Dietary Guidelines for Americans. AB - Forty-three menus that were to be used in a diet manual were designed to meet the requirements of a specific diet; provide 2,200 to 2,400 kcal, unless energy restricted; meet the 1990 Dietary Guidelines for Americans; meet current recommendations for sodium (2g to 3 g/day), cholesterol (< or = 300 mg/day), and fiber (20g to 30 g/day); and meet or exceed the highest level for adults in the 1989 Recommended Dietary Allowances (RDAs). In addition, regular and low-fat, low cholesterol menus for 1 week were collected from 11 hospitals throughout Arkansas. Menus were analyzed for energy, cholesterol, and 18 nutrients. Only 11% of the menus met the RDA for zinc. Half of the menus did not meet the RDA for vitamin B-6 and one third did not meet the RDA for iron. Zinc content of the menus was positively correlated (P < .001) with protein (r = .73) and with beef (r = .45). Vitamin B-6 was positively correlated with protein (r = .44, P < .001) and with all meat (r = .38, P < .01). Regular and low-fat, low-cholesterol hospital menus had the same nutrient inadequacies because they did not differ in total servings from any food group. These data indicate that the public may have difficulty choosing a diet that meets both the Dietary Guidelines and the RDAs. PMID- 7860948 TI - The new nutrition facts label in the print media: a content analysis. AB - A content analysis was conducted to evaluate the coverage of the new food labels in the print media from December 1, 1992, to August 30, 1993. We used newspaper, magazine, and health newsletter indexes to identify 59 newspaper articles, 16 magazine articles, and 7 health newsletter articles for examination. Articles were evaluated by four trained coders using a pretested coding form addressing 35 aspects of the nutrition label coverage. Twenty percent of articles were double coded with at least 80% coder reliability. Analysis of the data indicated that health newsletters covered the topic in the most detail, followed by magazines and then newspapers. Ten of 59 (17%) newspaper articles named and defined the term percent daily value, whereas 6 of 7 (86%) health newsletter articles and 9 of 16 (56%) magazine articles provided this information. Analysis of quotes in the articles indicated that more than half of the quotes were from government and industry officials. In contrast, quotes from college and university faculty represented only 5% of total quotes and quotes from dietitians represented less than 8% of total quotes. Coders identified several errors resulting from oversimplification of complex concepts. These findings suggest that dietitians need to increase their exposure with the media and help the media translate complex nutrition labeling information to the public. PMID- 7860949 TI - Folic acid improves phenytoin pharmacokinetics. AB - Phenytoin (PHT) therapy to control seizures decreases serum folate levels in half of epileptic patients, thus increasing the risk of folate depletion. Supplementation with folic acid prevents deficiency but also changes PHT pharmacokinetics. Kinetic monitoring of PHT when folic acid is provided as a supplement has not been reported in women of child-bearing age. This study of six fertile women examined the interdependence of PHT and folic acid in a randomized crossover study of two treatments: treatment 1 consisted of 300 mg sodium PHT per day and treatment 2 consisted of 300 mg sodium PHT plus 1 mg folic acid per day. Dietary folic acid intake was calculated daily. During treatment 1, serum folate level decreased 38.0 +/- 18.6% (mean +/- standard deviation) and serum PHT concentration was in the low therapeutic range (43.92 +/- 14.52 mumol/L). During treatment 2, serum folate level increased 26.0 +/- 33.4%, and serum PHT level (39.04 +/- 14.16 mumol/L) was similar to that in treatment 1. Only one subject attained PHT steady state during treatment 1, but four subjects achieved steady state during treatment 2. Dietary folate intakes during treatments 1 and 2 were not significantly different. This study suggests an interdependence between PHT and folic acid and supports the observation that fertile women treated with PHT require folic acid supplementation to maintain a normal serum folate level. PMID- 7860950 TI - Local dietetic associations can facilitate collaborative clinical practice research. PMID- 7860951 TI - Who's at risk in Washington State? Demographic characteristics affect nutritional risk behaviors in elderly meal participants. PMID- 7860952 TI - Herbal tea: an alternative to regular tea for those who form calcium oxalate stones. PMID- 7860953 TI - Position of the American Dietetic Association and the Canadian Dietetic Association: Women's health and nutrition. PMID- 7860954 TI - Position of ADA, SNE, and ASFSA: school-based nutrition programs and services. PMID- 7860955 TI - Timely statement of the American Dietetic Association: dietary guidance for healthy children. PMID- 7860956 TI - Influencing spermicide use among low-income minority women. AB - Spermicides reduce the risk of a variety of sexually transmitted diseases (STDs) and hold promise for reducing the risk of human immunodeficiency virus (HIV) transmission. Many high-risk women are unaware that they are at risk for STDs and are unfamiliar with spermicides, however. A program promoting spermicides for the prevention of STDs was tested in a controlled intervention among low-income minority women seeking services in a public health family planning clinic. Women exposed to the intervention had more positive attitudes toward spermicides and used spermicides more than three times as often, on average, as control subjects. The best predictor of spermicide/condom use was knowledge of how to use spermicides correctly (OR 3.2, 95% CI 2.0, 5.0). Fear of acquired immune deficiency syndrome (AIDS) or STDs did not predict spermicide use. This study demonstrates that brief interventions in waiting areas of public health clinics can have a significant impact in helping women protect themselves from HIV and STDs. PMID- 7860957 TI - Teaching women's issues in psychiatric residency: residents' attitudes. AB - There is increasing interest in psychiatry in women's and gender issues. This article evaluates psychiatric residents' interest in women's issues during training. The authors surveyed residents at four psychiatric residency programs to evaluate their opinions on the teaching of women's issues. Residents rated this topic an important one, but felt training could be improved. The authors review one program's curriculum and suggest ways in which women's mental health issues might be incorporated into residency training. PMID- 7860958 TI - Women's health and managed care: implications for the training of primary care physicians. AB - The growth of managed care is changing the practice of medicine; it has a direct impact on the quality of care offered to women and may erode gains made in the field of women's health. Graduate medical education must be transformed if women's health is to be effectively represented in the evolving health care system. An interdisciplinary primary care specialty in women's health is the best strategy for preparing physicians to deliver cost-effective comprehensive care to women in a changing health care marketplace. PMID- 7860959 TI - Animal reproduction studies can provide specific information on teratogenicity and potential long-term reproductive effects of investigational drugs. PMID- 7860960 TI - Negative view of the anthology women, power and therapy. PMID- 7860961 TI - RU486 is not available in the United States. PMID- 7860962 TI - Does coffee consumption increase the risk of reproductive adversities? PMID- 7860963 TI - When female medical students are the majority: do numbers really make a difference? AB - According to Kanter's theory of group dynamics, when women constitute half or more of the population in a given setting, their interactions with their male peers are more balanced and they are in a better position to influence their colleagues' professional attitudes and behavior. The influence is only significant, however, if other structural factors favor attitude and behavioral changes. Using data obtained from a mail survey of 1,247 students (82.4% response rate) conducted at three levels of medical training in three medical schools where female students were in the majority, we compared male and female students on their professional attitudes. At entrance to medical school, women were more interested in the humanistic, psychosocial, and multidisciplinary components of the physician's role than their male colleagues. At the intermediate level, however, women's interest in humanistic and psychosocial issues was less pronounced and at the graduate level this gender difference was no larger present. These results are discussed in terms of their implications for medical training. PMID- 7860964 TI - Estrogen issues in relation to cardiovascular disease. PMID- 7860965 TI - Doctors and public authorities: the trend toward collaboration. AB - Insuring a population and managing its money require a comprehensive health care financing system. Many issues must be resolved, particularly the roles of the medical profession and its relationship with organizations of laymen in insurance carriers and in government. The spread of society-wide, third-party reimbursement produced conflicts with doctors over admission to practice, work rules, and pay in all countries. Eventually new arrangements were made to settle conflicts of interest and to ensure the harmonious operation of health care services. Policymakers and financial managers came to realize that the medical profession as a whole must be motivated to ensure the success of the system. Recently countries with statutory health insurance and direct public financing created new systems for negotiation and for joint decision making. Even some governments now agree to collaborate with doctors as virtual peers rather than to dictate rules and finance. The only exception is the United States, which will continue to have periodic conflicts until it crafts a joint decision-making system. The evidence comes from the author's first-hand field research over thirty years in the principal developed countries in Europe and North America. He interviewed informants, collected reports, and observed events for these topics primarily in Germany, France, the Netherlands, Great Britain, Canada, and the United States. PMID- 7860966 TI - The impact of intra-DRG severity of illness on hospital profitability: implications for payment reform. AB - We examined the relationship between variations in intra-DRG severity of illness classifications and hospital profitability. Unlike in previous studies, we created a direct hospital-level measure of severity, formed from MedisGroup severity scores. We estimated separate regression equations for total margin, operating margin, net revenue per admission, and expense per admission. We examined data for 201 Pennsylvania hospitals and found that hospital profits were inversely related to the severity of illness index. Expense per admission was positively related to severity; however the relationship between severity and net revenue per admission was not significant. The results suggest that hospitals with a more severe case mix may not recover the full costs of providing services. Thus payment reform should include adjustments for severity of illness. PMID- 7860967 TI - The success and repeal of the Medicare Catastrophic Coverage Act: a paradoxical lesson for health care reform. AB - Congress intended the Medicare Catastrophic Coverage Act (MCCA) of 1988 to reduce the risk for illness-related catastrophic financial losses in the elderly. The act was short-lived, facing repeal just one year after passage. Many elderly persons were convinced that the costs of the program outweighed the benefits. However nursing home payment provisions of the MCCA may have affected out-of pocket expenses paid by the elderly for long-term care more than consumers realized at the time of repeal. A transmittal memorandum, issued by the Health Care Financing Administration independent of Congressional action, enhanced consumers' ability to qualify for Medicare nursing home benefits. We investigated the effects of the Medicare policy change on nursing home payer mix and out-of pocket expenses in 489 Pennsylvania nursing homes. We found that substantial shifts in payer mix from self-pay to Medicare payment sources occurred, reducing out-of-pocket expenses. Unfortunately the debate over the MCCA's repeal did not include discussion of the improved nursing home benefit structure. These findings, and the fate of the MCCA legislation, reinforce the importance of comprehensive information and clear communication in promoting health care reform. PMID- 7860968 TI - Scientism and economism in the regulation of health care. AB - As health care costs continue their apparently relentless rise, it seems to be universally perceived that the United States and western Europe are gripped by a cost crisis. To resolve the apparent crisis, U.S. and western European governments and third-party payers are turning increasingly to a new positivist discipline, called health services research, for which neoclassical health economics is the dominant discourse. However this discipline may actually reinforce the strength of biomedical positivism and the concomitant technological imperative. Like biomedicine, health services research is technologically driven, dependent on "advances" that generate more comprehensive and therefore more "accurate" data. Accordingly, just as biomedicine causes health care workers and patients to depend on technologies for diagnosis and treatment, health services research instills in the body politic dependence on technocratically conceived solutions for political problems. Moreover, because biomedicine and health services research share positivist epistemic and methodological premises, both objectify the subjects they study, abstract those subjects from context, and thereby ignore the cultural dimensions of the problems at hand. Rather than inculcate an ethic and practice in which medicine focuses on the meaning of illness for a life, a cultural phenomenon, this form of positivism strengthens the tendency to reject meaning in favor of the causes and course of disease and the abstracted probability of its occurrence. Accordingly health services research and the forms of regulation with which it is allied threaten to overwhelm the medical humanities movement. Furthermore this scientism precludes the institutionalization of political forums in which we can deliberate on the meaning of medicine, health, and death in our lives. PMID- 7860969 TI - The new science of medicine. PMID- 7860970 TI - Two fringe discourses in search of influence on policy. PMID- 7860971 TI - Birth choices, the law, and medicine: balancing individual freedoms and protection of the public's health. AB - To many Americans, the idea of home birth, the use of a "direct-entry midwife," or both seem archaic. Although much of the professional medical community disapproves of either, state laws regarding birth choices vary dramatically and are not necessarily based on empirical findings of childbirth outcomes. Public health practitioners, policymakers, and consumers view childbirth from the perspectives of safety, cost, freedom of choice, quality of the care experience, and legality, yet the professional, policy, and lay literatures have not offered an unemotional, balanced presentation of evidence. Reviewing the full spectrum of literature from the United States and abroad, we present a Constitutional medical legal analysis of whether home birth with direct-entry midwives is in fact a safe alternative to physician-attended hospital births, and whether there is a legal basis for allowing alternative health policy choices is such an important yet personal family matter as childbirth. The literature shows that low- to moderate risk home births attended by direct-entry midwives are at least as safe as hospital births attended by either physicians or midwives. The policy ramifications include important changes in state regulation of medical and alternative health personnel, the allowance of the home as a medically acceptable and legal birth setting, and reimbursement of this lower-cost option through private and public health insurers. PMID- 7860972 TI - State responses to the Medicaid spending crisis: 1988 to 1992. AB - In recent years the growth of Medicaid spending has been a serious state budgetary problem. Between 1988 and 1992, state Medicaid expenditures increased at an average annual rate of 21 percent. Even when accounting for funds from special revenue programs, such as provider tax and donation programs, state Medicaid spending increased by 16 percent each year between 1988 and 1992, which is far higher than in previous years. This rapid expenditure growth occurred when states were having economic slowdowns and facing fiscal pressures in many other areas. Using a case study approach, we investigated the strategies used by nine states to address the recent surge in Medicaid spending. Despite fiscal pressures, the states generally avoided large-scale cutbacks in Medicaid. Instead they implemented a wide range of budgetary actions to reduce the effect of Medicaid growth, including increment program cutbacks, constraining other budgetary sectors, shifting program costs to the federal government, and raising state taxes. PMID- 7860973 TI - Integration of community-based services for the severely mentally ill and the structure of public funding: a comparison of four systems. AB - Despite strong interest by health care services researchers in studying community based service delivery to persons with severe mental illness, few understand the relationship between the structure of public funding and differences in how mental health care delivery systems are organized. In particular, the structure of public funding may have a substantial effect on the nature and extent of integration among the various service providers that comprise a community's delivery network. Such an understanding is critical if mental health policymakers are to use their influence on funding to guide the structure of service delivery. To investigate this issue, we compared community mental health care systems in four U.S. cities. We found that services will be integrated regardless of the structure of public funding but that the structure of integration among providers will be affected. Specifically strong fiscal control by the state is conducive to delivery systems that are integrated through the core mental health care agency in a community, whereas weak fiscal control is more likely to result in decentralized integration among system providers. PMID- 7860974 TI - ISMA program helps with practice-related problems. PMID- 7860975 TI - ISMA presents results of strategic health survey. PMID- 7860976 TI - Survey of influencing factors to a career in family medicine. PMID- 7860977 TI - Acquired respiratory failure in critically ill patients. AB - With increasing survival rates from acute medical or surgical emergencies a new form of peripheral neuropathy, CIP, has been recognized. CIP can be seen only in patients who are considered to be critically ill; therefore, it invariably occurs in the ICU. Typically, initial symptoms begin with transient (hours to a few days) septic encephalopathy followed by generalized weakness, manifested in weaning failure, limb weakness and hyporeflexia. Diagnosis is confirmed by an EMG. CIP should be considered in any elderly patient with sepsis and prolonged respiratory muscle weakness. Prognosis is poor in severe cases, in which the EMG also shows severe axonal degeneration. In milder forms, fair to good recovery is expected within weeks. Management includes treatment of sepsis, normalization of failing organ function, physical therapy and proper nutrition. PMID- 7860978 TI - Doctor explains PO, PHO formation. Interview by Bob Carlson. PMID- 7860979 TI - Gay marriage: a civil right. AB - This article describes the author's efforts to secure marriage rights for same sex couples in the District of Columbia. The importance of such rights are described in terms of their benefits to partners in areas such as inheritance, taxation, and benefit to society. It is argued that refusal to recognize same-sex marriages is not justified by statute and that discrimination on the basis of sex violates the District's Human Rights Act. Certain prior court cases, moreover, affirm the moral logic for extending marriage rights to same-sex couples. PMID- 7860980 TI - The military ban and the ROTC: a study in closeting. AB - This article examines reasons for university involvement in protesting ROTC policies discriminatory toward lesbians and gay men. The formal exclusion of lesbians and gay men from the military permits not only the abuses in selective enforcement of the policy and considerable economic costs to maintain it, but also contributes to the perpetuation of the closet. Closeting is not a phenomenon chosen by lesbians and gay men for reasons of their own, and it rewards deceit, penalizes honesty, blames lesbians and gays for the mistrust of others, and effects a psychological division ("doubling") of individual identity and corrupts individual responsibility. For these reasons, university educators, as committed to the advance of truth, have an obligation to protest ROTC compliance with discriminatory policies. PMID- 7860981 TI - A moral justification for gay and lesbian civil rights legislation. AB - This essay explores, in two parts, the problems of justifying civil rights legislation for gays, lesbians, and bisexuals. Part I shows that discrimination against gays and lesbians at least in respect to employment, housing, and public accommodations is an evil unsupported by ethical traditions in utilitarianism, rights theory, and communitarianism. It also shows that two theories, Kantian theory and natural law theory, which do support such discrimination on the claim that homoerotic behavior is universally or objectively immoral only do so because of a failure to make precise the concept of "natural" which underlies those theories. Part II argues that anti-discrimination legislation is both an appropriate and effective means to promote the idea that discrimination against lesbians and gays in respect to most employment, housing, and public accommodations is sufficiently injurious to both individuals and society that it should not be tolerated. The section also explains how such legislation might succeed practically in eliminating discrimination in these areas. PMID- 7860982 TI - Gay rights and affirmative action. AB - While affirmative action programs exist for a number of groups, little serious consideration has been given to the establishment of such programs for gay men and lesbians. This essay argues that many of the conditions that justify current affirmative action programs would also justify their extension to gay people, both in terms of compensation for injuries suffered and in terms of benefit to both individuals and society generally. It is argued that anti-discrimination policies are hard to enforce and in any case would be inadequate to redress many of the wrongs suffered by gays and lesbians. It is concluded that programs favoring gay visibility are morally justified. PMID- 7860983 TI - Explaining homosexuality: philosophical issues, and who cares anyhow? AB - Standard behavioral and biological attempts to explain the etiology of homosexuality are surveyed. These include genetic, physiological (e.g., hormonal), constitutional (e.g., wrong pubic hair configurations), childhood experience, parenting, and psychoanalytic accounts. These are criticized from a number of perspectives, including inadequate conceptualization of homosexuality and heterosexuality. The use of path analysis to assess etiological accounts is examined, with particular attention being paid to the Kinsey Institute's Sexual Preference efforts. Drawing from the sociology of science, recent philosophical work on the growth of scientific knowledge, and historical considerations, the legitimacy of homosexual etiology as a scientific research question is examined. It is argued that homosexual etiology is a degenerative research program. The research program's conceptual crudity with respect to sexual identity and sexual orientation precludes it from making any scientific contribution. Thus the claim that homosexual etiology is a legitimate scientific issue is plausible only against the background of a set of late Victorian normative assumptions about "normal love," some surrogate thereof, or a political agenda. Implications of the homosexuality etiology case study for more general philosophical treatments of explanation are considered briefly. PMID- 7860984 TI - The relevance of scientific research about sexual orientation to lesbian and gay rights. AB - This essay considers the way in which scientific research is relevant to questions of lesbian and gay rights. It is specifically argued that such research is not relevant to these kinds of arguments because its results about the origins of sexual orientation do not necessarily-and should not be taken to-imply conclusions about moral entitlements. Questions about the moral and civic entitlements of gay men and lesbians are not bolstered or advanced by reference to biological accounts of sexual orientation. This is not to suggest, however, that research into the origins of sexual orientation is objectionable, only that it does not have the significance for moral rights that some have claimed. PMID- 7860985 TI - The closet and the ethics of outing. AB - Because social circumstances have changed, the question of outing has assumed an importance unknown in a time when homosexuality was a guarded secret. This essay describes the evils of the closet in terms of its affronts to the worth of gay men and lesbians. While outing might appear as a repudiation of the closet, this essay argues that not all outing is justified. On the other hand, the article also rejects those arguments that criticize outing as a violation of privacy as well as arguments that defend outing as no violation of others' rights. PMID- 7860986 TI - Fixation and regression in the psychoanalytic theory of homosexuality--a critical evaluation. AB - This essay evaluates the notions of fixation and regression in the psychoanalytic theoretical conceptualization of homosexuality. Charles Socarides has had a central role in formulating the most prominent and influential psychoanalytic metapsychological understanding of homosexuality in recent years and for that reason this essay focuses principally on him. The concepts of fixation and regression are central to his understanding and I argue that the evolution of these concepts in contemporary usage renders them irrelevant to formulating the current psychoanalytic understanding of homosexuality and that their continued use by analysts reflects a negative attitude toward homosexual behavior on the part of Socarides and many other analysts that stems from an extremely narrow and idealized conception of human development. PMID- 7860987 TI - Homophobia and the moral authority of medicine. AB - This essay identifies ways in which medicine expresses and legitimizes homophobic values. Examples of such homophobia are identified in the treatment of people with HIV, moralistic interpretations of people with AIDS, certain conceptions about ways in which HIV is transmitted, media representations of AIDS, and even in the way in which medicine's "objectivity" reinforces a moral view inimical to gay men, lesbians, and bisexuals. It is concluded that the notion of medical objectivity and traditional conceptions of the ethics of health care hinder an appreciation of the ways in which medicine presumes and perpetuates homophobic values. PMID- 7860988 TI - Privacy and the ethics of outing. AB - This essay argues that, in the absence of a compelling justification, outing is immoral as a violation of privacy. Reasons for respecting privacy involve fundamental interests which encompass information about gay and lesbian sexual orientation. Utilitarian defenses of outing are criticized, as is Richard Mohr's analysis of privacy and defense of outing in the name of dignity. Mohr's claim that gay or lesbian sexual orientation does not fall within the scope of the right to privacy is rejected. PMID- 7860989 TI - Outing, truth-telling, and the shame of the closet. AB - This essay examines the nature of being in the closet, coming out, and the practice of outing. It is argued that no general rule against outing can be maintained since outing others may be defensible as one pursues one's own legitimate legal and moral interests. Neither does privacy extend to all aspects of human life which someone may wish to keep secret, especially if information about sexual orientation is not obtained in any immoral way. Withholding information about sexual orientation may sometimes be justified but on grounds of secrecy and not in a way that always forbids outing. The shame and degradation of the closet are evils, but outing is not necessarily their solution, though any loss of "privacy" entailed by coming out of the closet can be more than compensated by the rewards of casting off implications of worthlessness. PMID- 7860990 TI - Homosex/ethics. AB - Against the view that homoeroticism requires any special justification or consideration, this essay argues that homoeroticism is morally unproblematic in itself and that its genuine moral significance resides in illuminating the nature and meaning of human relations. Seen as a form of language, homosex shares common moral justification with heterosex as a bearer of human meanings and intentions. Thus understood, homosex is an important moral good as a language that expresses human meanings in ways that are not otherwise possible. PMID- 7860991 TI - Coming out, being out, and acts of virtue. AB - We examine three philosophical models for (gay) self-identity: utilitarianism (exemplified by Eichberg), deontologism (Mohr), and individualism (Spinoza). The first two, we argue, overlook the personal and multi-faceted nature of social relations. We argue that the framework of methodological individualism is better suited to deal with the issues of self-identity as they affect questions of whether, when, and how to come out, and being out. This framework suggests that there is no moral principle which could apply universally in regard to being out and that there are common situations in which it is not morally appropriate to come out or to be out at all. PMID- 7860992 TI - Microsatellite instability in human non-melanoma and melanoma skin cancer. AB - Microsatellite instability secondary to replication errors (RER), characterized by length changes at repetitive loci scattered throughout the genome, is a recently recognized genetic mechanism important in the development of some human cancers. Although RER has been reported in sebaceous gland tumors from patients with the Muir-Torre syndrome, the frequency of RER in human non-melanoma and melanoma skin cancers is not known. In this study, we investigated the importance of RER in human skin carcinogenesis. RER was identified in three of four actinic keratoses from a patient belonging to a kindred with documented Muir-Torre syndrome, which indicates that defective DNA replication may contribute to skin cancer development in such patients. Examination of a series of tumors from patients without Muir-Torre, including 137 skin cancers (47 basal cell carcinomas, 49 squamous cell carcinomas, and 41 primary malignant melanomas), 19 actinic keratoses, and 20 cases of Bowen's disease, using 10 or more microsatellite markers, identified repeat-sequence instability in less than 5% of the tumors studied. In six of the eight tumors, the sole change was an alteration 2 base pairs in length at a single locus. One patient with a squamous cell carcinoma showed changes at multiple loci suggesting defective mismatch repair. Although the low frequency of RER found in this study of a large series of human skin tumors suggests that this phenomenon is uncommon in patients with skin cancer, the identification of RER at multiple loci in two patients suggests that error-prone replication may be important in skin cancer development in some individuals. PMID- 7860993 TI - Inhibition of melanoma growth by adenoviral-mediated HSV thymidine kinase gene transfer in vivo. AB - To assess the potential of an in vivo, adenovirus-mediated gene therapy approach for the treatment of malignant melanoma, the efficacy of adenovirus-mediated herpes simplex virus thymidine kinase gene (HSV-Ek) transfer and administration of ganciclovir (GCV) was investigated using a nude mouse model. Initially, B16 murine melanoma cells were efficiently transduced in vitro by a recombinant replication-defective adenovirus containing the HSV-tk gene (ADV/RSVtk), and rendered sensitive to cell killing by 10 micrograms/ml GCV. A significant "bystander effect" was observed at low multiplicity of infection in comparison of cell killing to control B16 transduction by adenovirus containing the beta galactosidase gene (ADV/RSV-beta-gal). In vivo, melanomas established from subcutaneous injection of 4 x 10(5) B16 cells were injected after 14 d with 1 x 10(10) ADV/RSV-tk viral particles. Subsequent treatment for 6 d with GCV resulted in an inhibition of melanoma growth, with an approximately 40-50% reduction in melanoma volume in comparison to controls in repeated experiments. These data demonstrate that adenovirus-mediated gene transfer can function as an efficient delivery system to reduce established tumor burden in vivo. This result may hold significant promise for the development of effective in situ gene therapy for melanoma in humans. PMID- 7860994 TI - Expression of the tumor necrosis factor gene by dermal fibroblasts in response to ultraviolet irradiation or lipopolysaccharide. AB - To examine the effects of different wavelengths of ultraviolet (UV) radiation on tumor necrosis factor (TNF) production, we took advantage of mice carrying a chloramphenicol acetyl transferase (CAT) reporter transgene bearing the entire TNF promoter and 3'-untranslated region. Aside from constitutive expression in the thymus, CAT activity was detected only in locally UVB- or UVC-irradiated skin. After UVB irradiation, markedly greater amounts of CAT activity were traced to the dermis rather than the epidermis; by contrast, almost all CAT activity was localized to the epidermis after UVC irradiation. Fibroblasts have not been shown previously to express the TNF gene, i.e., the TNF gene is highly methylated and inaccessible to exogenous modulation in 3T3 fibroblasts. However, the present report reveals that cultured dermal fibroblasts are capable of producing both CAT and TNF in response to treatment in vitro with either UVB irradiation, UVC irradiation, or lipopolysaccharide. These findings indicate that dermal fibroblasts may serve not only as a target for but also as a source of TNF. PMID- 7860995 TI - Pemphigus foliaceus and pemphigus vulgaris autoantibodies react with the extracellular domain of desmoglein-1. AB - Pemphigus foliaceus is associated with an autoimmune response against desmoglein 1; however, the fine specificity of these autoantibodies and the role that they play in pathogenesis have not yet been elucidated. In an attempt to develop a system to facilitate the detection and characterization of this antigen/antibody system, recombinant human desmoglein-1 was expressed in COS-1 cells, a mammalian epithelial cell line. The desmoglein-1 transgene product was shown to be expressed on the surface of the COS-1 cells in the appropriate transmembrane orientation. All pemphigus foliaceus sera (endemic form, n = 24; nonendemic form, n = 7) reacted strongly with nonpermeabilized desmoglein-1-transfected cells, exhibiting a punctate cell-surface staining pattern. This reactivity against the desmoglein-1 ectodomain was predominantly an IgG4-restricted response and was calcium dependent. Ten of 18 pemphigus vulgaris sera also reacted with the extra cellular domain of recombinant desmoglein-1. Use of this eukaryotic expression system should greatly facilitate further characterization of the anti-desmoglein 1 autoimmune response associated with pemphigus foliaceus and pemphigus vulgaris and may aid in determining its pathogenic relevance. PMID- 7860996 TI - Regulation of transgenic class II major histocompatibility genes in murine Langerhans cells. AB - I-E is a class II major histocompatibility complex molecule normally expressed by Langerhans cells. A series of transgenic mice were developed previously that carry E alpha d gene constructs with promoter-region deletions that cause expression of I-E by different cell types when maintained on a B6 (I-E[-]) genetic background. To study cis-acting gene sequences that regulate expression of class II proteins by Langerhans cells, we identified transgenic I-E expression by tissue immunoperoxidase staining and by epidermal cell suspension immunofluorescence cytometry. Mice with a transgene containing 1.4 kilobase pairs (kb) of flanking sequence 5' to the E alpha initiation site expressed barely detectable levels of I-E on a tiny percentage of Langerhans cells, indicating that sequences promoting Langerhans cell expression of E alpha exist between 2.0 and 1.4 kb 5' of the E alpha initiation site. Removal of an additional 170 bp of 5' flanking sequence caused near-normal levels of expression by approximately one third of epidermal Langerhans cells, which contrasts with studies that showed minimal transgene expression by splenic dendritic cells in these animals. Thus, sequences between 1.4 and 1.23 kb 5' of the E alpha initiation site decrease expression of I-E by epidermal Langerhans cells, but enable I-E expression by splenic dendritic cells. These studies identify Langerhans cell-specific regulatory sequences and genetic regions controlling major histocompatibility complex class II gene expression in Langerhans cells and splenic dendritic cells. The genetic regions identified may be particularly important because differential regulation of class II major histocompatibility complex protein synthesis by Langerhans cells and dendritic cells may be crucial to immune functions of intact animals. PMID- 7860997 TI - Failure to detect interleukin (IL)-3 mRNA or protein in human keratinocytes: antibodies to granulocyte macrophage-colony-stimulating factor or IL-6 (but not IL-3) neutralize "IL-3" bioactivity. AB - Interleukin (IL)-3-like bioactivity has been found in culture supernatants from human and murine keratinocytes. However, there is controversy as to the presence of IL-3 mRNA in human keratinocytes. Using highly sensitive reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay techniques, we examined human keratinocytes from four different donors (neonatal foreskins) and were unable to detect IL-3 mRNA or IL-3 protein. Despite successful amplification of DNA from an IL-3 cDNA, no product could be obtained by amplification of keratinocyte RNA treated with reverse transcription-polymerase chain reaction. Analysis of concentrated (up to 50-fold) supernatants failed to detect IL-3 protein by enzyme-linked immunosorbent assay. Because ultraviolet radiation up regulates many cytokines, we irradiated human keratinocytes with 300 J/m2 ultraviolet B and collected supernatants 24 h post-irradiation. Supernatants concentrated 50-fold were also negative for IL-3 protein by enzyme-linked immunosorbent assay. When assayed on the IL-3-responsive M-07e cell line, unirradiated supernatants stimulated M-07e proliferation 22-fold over background levels. Irradiated supernatants stimulated M-07e proliferation 128-fold. Neither the unirradiated nor the irradiated supernatant activity could be neutralized with antibody to human IL-3. However, incubation of irradiated supernatants with antibody to granulocyte macrophage-colony-stimulating factor (GM-CSF) reduced the M-07e proliferation by 90%. Antibodies against GM-CSF and IL-6 completely abrogated proliferation. Reverse transcription-polymerase chain reaction confirmed a concomitant elevation of IL-6 (2.6- to 5.6-fold) and of GM-CSF mRNA (2.7- to 4.3-fold) at 6 and 24 h after ultraviolet B irradiation in keratinocytes, but no IL-3 amplification products could be detected. IL-3 mRNA was also not detected in adult keratinocytes. Even after stimulation by IL-1 alpha, tumor necrosis factor-alpha, or phobol myristate acetate, IL-3 mRNA was not detected in either neonatal or adult human keratinocytes. We have been unable to detect IL-3 mRNA or IL-3 protein in human keratinocytes. The IL-3-like activity in human keratinocytes is mainly due to GM-CSF, with a small contribution from IL-6. PMID- 7860998 TI - Expression of cathepsin D in primary and metastatic human melanoma and dysplastic nevi. AB - High levels of cytosolic cathepsin D expression have been associated with poor prognosis in breast cancer node-negative patients. In this work, we provide evidence that three cell lines established from human metastatic melanomas--IIB MEL-J, IIB-MEL-LES, and IIB-MEL-IAN--express high levels of procathepsin D mRNA. IIB-MEL-J cells secreted into the conditioned media about 30% of the newly synthesized protein, which was active at acidic pH. Melanoma tumors arising in nude mice after injection of the three different cell lines expressed high levels of procathepsin D mRNA. Moreover, 13 human metastatic melanomas expressed variable levels of procathepsin D mRNA. To study the possible association between cathepsin D expression and melanoma development, samples corresponding to 10 primary tumors, 11 metastatic melanomas, 10 dysplastic nevi, 27 nevocellular nevi, and normal melanocytes were studied by immunohistochemistry for cathepsin D specific staining. We found that cathepsin D was expressed in all of the dysplastic nevi and primary and metastatic melanomas tested but in only 18% of nevocellular nevi (five of 27), whereas normal melanocytes showed no cathepsin D expression. The overall data indicate that cathepsin D is expressed at a high level by melanoma cells, and because of its expression in preneoplastic lesions, it may be associated with melanoma development. PMID- 7860999 TI - Topical nutrients promote engraftment and inhibit wound contraction of cultured skin substitutes in athymic mice. AB - Routine treatment of burns with cultured skin substitutes (CSS) has been limited by poor engraftment and by scarring. Hypothetically, topical application of essential nutrients and/or growth factors may support epithelial survival temporarily during graft vascularization. CSS, composed of human epidermal keratinocytes and dermal fibroblasts attached to collagen-glycosaminoglycan substrates, were incubated for 19 d in media optimized for keratinocytes. CSS, human xenografts, murine autografts, or no grafts were applied orthotopically to full-thickness skin wounds (2 x 2 cm) in athymic mice. Wounds were irrigated for 14 d with 1 ml/d modified cell culture medium or with saline containing epidermal growth factor, or were treated with dry dressings. After 6 weeks, treated sites were scored for percentage original wound area (mean +/- SEM) and percentage HLA ABC-positive healed wounds [(number positive/n) x 100], and tested for significance (analysis of variance, p < 0.0001; Tukey test, p < 0.05). The data showed that CSS irrigated with nutrient medium were not statistically different in wound area (67.8 +/- 5.1%) from murine autografts (63.3 +/- 2.9%) but were statistically larger than human xenograft, no graft, or CSS treated with saline irrigation or dry dressings. HLA-ABC expression was 100% in CSS with nutrient irrigation, 86% in CSS with saline irrigation, 83% in CSS without irrigation, and 75% in xenografts with nutrient irrigation. These findings suggest that availability of essential nutrients supports keratinocyte viability during graft vascularization of CSS. PMID- 7861000 TI - Involvement of granulocytes and the adhesion receptors intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in tissue inflammation induced by Th2-type helper cells. AB - We reported recently that subcutaneously injected, anti-CD3 epsilon-pulsed polyclonal Th2 cells mediate interleukin-4-dependent local tissue inflammation. Because a prominent polymorphonuclear infiltrate was observed in the lesions at the time of maximal tissue swelling, we investigated the involvement of polymorphonuclear leukocytes and their adhesion molecules lymphocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) in Th2-cell-mediated inflammation. Pretreatment of recipient mice with a depleting monoclonal antibody to neutrophils or with blocking antibodies to LFA-1 or to ICAM-1 completely abrogated tissue swelling in Th2-cell-mediated inflammation. Granulocyte infiltration at 6 h was also inhibited by the antibodies to neutrophils and to ICAM-1, but not by that to LFA-1. Tissue swelling mediated by Th1 cells had different kinetics and was not prevented by administration of anti neutrophil antibody: maximal edema formation occurred at 24-48 h, when the predominant cellular infiltrate was mononuclear. Because the Th1-cell-induced infiltrate at 6 h also consisted of granulocytes but was not associated with pronounced edema, the mere presence of infiltrating polymorphonuclear leukocytes seems not to be sufficient to induce edema. Because edema but not granulocyte infiltration was inhibited by anti-LFA-1 and because anti-LFA-1 antibodies are known to inhibit several functions of neutrophils, our results suggest that, in inflammation mediated by Th2 cells, granulocytes induce edema through their activation and/or degranulation. PMID- 7861001 TI - Differentiation-induced enhancement of the ability of cultured human keratinocytes to suppress oxidative stress. AB - Human keratinocytes in culture were harvested at different stages of differentiation. Both the level of antioxidants and the response of cells to oxidative stress were measured as a function of growth and differentiation. As the keratinocyte cultures became confluent and began to differentiate, the cellular levels of glutathione, glutathione peroxidase, glutathione S transferase, and glucose-6-phosphate dehydrogenase increased. This higher level of antioxidants was maintained until the cells began to lose viability. Further, as the keratinocyte cultures began to differentiate, they became more resistant to the toxic effect of cumene hydroperoxide in terms of both of the rate of loss of cell mass and total glutathione and of the rate of decline in the activity of oxidation-sensitive enzymes. To determine how tightly the observed effects are linked to the calcium-dependent aspects of differentiation and to rule out effects related to time in culture, the cells were switched from 1.2 mM Ca++ to 0.03 mM Ca++ to suppress Ca(++)-dependent differentiation. After 4 d, these cells were then treated with 0.5 mM cumene hydroperoxide. The switch to 0.03 mM Ca++ blocked the normal increases in both glutathione peroxidase and glucose-6 phosphate dehydrogenase activities. Further, cells in 0.03 mM Ca++ had reduced resistance to cumene hydroperoxide relative to cells cultured for the same length of time in 1.2 mM Ca++. This indicates that there is a differentiation associated, Ca(++)-specific increase in both the level of antioxidants and in tolerance to organic hydroperoxides. PMID- 7861002 TI - The phototumorigenic potential of broad-band (270-350 nm) and narrow-band (311 313 nm) phototherapy sources cannot be predicted by their edematogenic potential in hairless mouse skin. AB - The new Philips TL01 narrow-band (311-313 nm) and conventional broad-band (e.g., Philips TL12; 270-350 nm) sources are effective for psoriasis phototherapy, for which treatment regimens are based on a predetermined minimal erythema dose. TL01 phototherapy treatment times are approximately half those with TL12 for psoriasis, whereas the cumulative exposure doses at clearing are similar. We compared the phototumorigenic potential of TL01 and TL12 radiation in mouse skin. Groups of albino Skh-1 hairless mice were exposed for 5 d/week at three dose levels. At each dose level, TL12 and TL01 doses were equally edematogenic. At each dose level, TL01 radiation was significantly more effective at producing first tumors of 1 mm in diameter and multiple tumors. At the lower two dose levels, TL01 radiation produced a significantly greater proportion of squamous cell carcinomas. This study demonstrates that TL01 radiation is more phototumorigenic than TL12 radiation at equally edematogenically weighted doses. This is in contrast with previous reports that edema production by polychromatic sources is predictive of their phototumorigenic effect in Skh-1 mice. The absolute cumulative TL12 dose needed to induce tumors was much less than that for TL01 radiation. The possibility of increased tumor risk with TL01 phototherapy should be considered but must be balanced against the high phototherapeutic efficacy of this source, short treatment times, and the low cumulative doses necessary for clearing of psoriasis. PMID- 7861003 TI - Ultraviolet B-induced local immunosuppression of contact hypersensitivity is modulated by ultraviolet irradiation and hapten application. AB - The induction of contact hypersensitivity is suppressed when hapten is applied topically to an area irradiated by ultraviolet B (UVB). There is no standardized procedure to induce this local immunosuppression by UVB. We investigated the effects of the following factors on induction of dinitrofluorobenzene contact hypersensitivity in mice. UVB dose, divided UVB exposure, timing of sensitization after irradiation, hapten concentration, hapten volume (application area), sex, age, and simultaneous sensitization on UV-exposed and nonexposed skin. The suppression was enhanced by increasing the UVB dose. When 100 mJ/cm2 of UVB was irradiated, divided daily exposure (25 mJ x 4 d) was more suppressive than single exposure (100 mJ x 1 d). Sensitization 2 d after irradiation (100 mJ/cm2) induced suppression most effectively. When 25 microliters of dinitrofluorobenzene solution was applied to exposed skin, higher concentrations induced lower suppression. When the total dose of hapten was kept constant (92 micrograms), the application of lower concentrations to large areas (0.25%, 25 microliters) caused stronger suppression than higher concentrations (1%, 6.25 microliters) to small areas. Simultaneous sensitization on UV-exposed and nonexposed skin revealed less suppression than sensitization only on exposed skin. The suppression of contact hypersensitivity was significantly greater in young than in old mice. These results provide details that may be useful in designing studies involving immunosuppression by UVB radiation. PMID- 7861004 TI - Autoantibodies from patients with cicatricial pemphigoid target different sites in epidermal basement membrane. AB - Indirect immunogold electron microscopy studies of cryofixed, freeze-substituted, and post-embedded normal human skin were performed to localize precisely the ultrastructural binding site of circulating autoantibodies from two groups of patients with cicatricial pemphigoid. One group of patients had circulating IgG autoantibodies that bound the dermal side of 1 M NaCl-split skin and immunoprecipitated epiligrin. The other group of patients had circulating IgG autoantibodies directed against the epidermal side of 1 M NaCl-split skin and showed no specific reactivity to any keratinocyte polypeptide by immunoprecipitation. IgG autoantibodies from all patients with anti-epiligrin cicatricial pemphigoid bound the lowermost aspect of the lamina lucida at its interface with the lamina densa; the greatest staining was seen beneath and beside hemidesmosomes. In contrast, IgG from cicatricial pemphigoid patients whose autoantibodies bound the epidermal side of 1 M NaCl-split skin localized to hemidesmosomes and the junction between hemidesmosomes and the plasma membranes of basal keratinocytes. Although the latter staining pattern is similar to that observed with anti-BPAG2 autoantibodies, sera from our patients with cicatricial pemphigoid did not bind BPAG2 in immunoprecipitation studies of radiolabeled human keratinocyte extracts or show immunoblot reactivity to a fusion protein corresponding to the immunodominant epitope of this polypeptide. These studies demonstrate the following: 1) Autoantibodies from patients with anti-epiligrin cicatricial pemphigoid consistently bind the lower lamina lucida at its interface with the lamina densa; and 2) other patients with the same phenotype may have IgG autoantibodies against yet-unknown epitopes in basal keratinocytes. PMID- 7861005 TI - Differential regulation of plasminogen activation in normal keratinocytes and SCC 4 cells by fibroblasts. AB - The plasminogen activator (PA)/plasmin system is thought to be involved in processes such as tumor invasion and wound healing, during which epithelial and mesenchymal cells come close together. However, information on regulation of the PA/plasmin system during epithelial-mesenchymal interactions is scarce. Therefore, we examined the in vitro modulation of the production and activity of the components of the PA/plasmin system in squamous carcinoma cells (SCC-4) and normal human keratinocytes in relation to cell density and the presence or absence of fibroblasts (3T3 cells). There was an inverse relation between cell density and mRNA expression for urokinase-type plasminogen activator (u-PA) and u PA receptor in both SCC-4 cells and keratinocytes. In addition, such a relation was found for plasminogen activator inhibitor types 1 (PAI-1) and 2 (PAI-2) in SCC-4 monocultures, but not in keratinocyte monocultures. In contrast to monocultures, variation of cell density did not affect the mRNA expression of the components of the PA/plasmin system in cocultures of SCC-4 cells or keratinocytes with 3T3 cells. However, the relative expression of mRNAs in co-cultures was clearly different from that in monocultures, especially at low cell density. For most of the components of the PA/plasmin system, a decrease in mRNA expression and u-PA receptor protein was observed at most cell densities, whereas for PAI-1 only in keratinocytes a marked increase was documented. Zymography of supernatants revealed that the levels of both free u-PA and PA-PAI were increased in SCC-4/3T3 co-cultures, whereas in keratinocytes/3T3 co-cultures, only levels of the PA-PAI complex were increased, while the amount of free u-PA activity decreased. This occurred despite the increase u-PA immunoreactivity and was probably caused by the markedly elevated levels of immunoreactive PAI-1. The results of the present study reveal that the production and synthesis of various components of the PA/plasmin system in keratinocytes and SCC-4 cells depend on the density of epithelial cells and are modulated by fibroblasts, probably through a direct cell-cell or cell-matrix contact. Fibroblast-induced modulations are similar in keratinocytes and SCC-4 cells except for the regulation of PAI-1, which is markedly enhanced only in keratinocytes. This suggests that the modulation of PA activity in the direct microenvironment may be different under physiologic and pathologic conditions. PMID- 7861006 TI - Partial characterization of matrix-associated serine protease inhibitors from human skin cells. AB - Serine protease inhibitors have important regulatory roles in angiogenesis, intravascular fibrinolysis, wound healing, and cell migration. In this study, the extracellular matrix secreted by cultured human keratinocytes, foreskin fibroblasts, and SV-40-transformed human skin fibroblasts was analyzed for serine protease inhibitors by substrate reverse zymography. We found that the extracellular matrix deposited by these cells contained three inhibitors (M(r) 33,000, 31,000, and 27,000). These inhibitors protected the degradation of gelatin by trypsin and elastase, and of casein by plasmin. In contrast, the gelatinolytic activities of thermolysin and papain were not inhibited. Compared to untreated cells, cells treated with phorbol 12-myristate 13-acetate showed a two- to 10-fold increase in the expression of these inhibitors. Cycloheximide and actinomycin D decreased the cellular expression of these inhibitors, suggesting the involvement of de novo protein and mRNA synthesis. Antitrypsin activity of these inhibitors was resistant to heat and sodium dodecylsulfate, but was lost after reduction of disulfide bonds. The inhibitors bound specifically to trypsin and could be eluted from a trypsin column in active form. Collectively, these data suggest that the extracellular matrix deposited by keratinocytes and dermal fibroblasts contains active serine protease inhibitors. PMID- 7861007 TI - Interferon-gamma coordinately upregulates matrix metalloprotease (MMP)-1 and MMP 3, but not tissue inhibitor of metalloproteases (TIMP), expression in cultured keratinocytes. AB - Matrix metalloproteases (MMP) constitute a family of proteolytic enzymes degrading extracellular matrix components. Their activity is inhibited by tissue inhibitors of metalloproteases (TIMP). Previous studies have demonstrated that various cytokines can modulate MMP and TIMP gene expression. In this study, we demonstrate that interferon-gamma coordinately upregulates MMP-1 (interstitial collagenase) and MMP-3 (stromelysin-1) gene expression in cultured keratinocytes, as determined at the mRNA steady-state levels, and this effect is dependent on on going protein synthesis. In contrast, there was no effect on TIMP-1 gene expression. Enhanced MMP-1 expression by IFN-gamma was also demonstrated at the protein level by Western analysis. Transient transfections with MMP-1 and MMP-3 promoter/reporter gene constructs revealed no response to IFN-gamma, whereas incubation of keratinocytes with this cytokine appeared to stabilize the MMP-1 mRNA, resulting in reduced turnover of the transcript. These data suggest that IFN-gamma enhances MMP gene expression at the post-transcriptional level. The altered MMP expression by IFN-gamma without concomitant effect on TIMP gene expression potentially leads to imbalance between these proteases and their inhibitors, and enhanced proteolytic activity may play a role in the remodeling of cutaneous tissue involving inflammatory processes, such as wound healing. PMID- 7861008 TI - Differences in involucrin immunolabeling within cornified cell envelopes in normal and psoriatic epidermis. AB - Epidermal keratinocytes form a cornified cell envelope (CE) beneath the plasma membrane during the late stages of differentiation. This CE is stabilized by cross linking of several precursor proteins, including involucrin. In psoriasis, the expression pattern of the precursor proteins is known to be deranged; involucrin expression is increased and loricrin expression is decreased. However, these changes have not been previously evaluated ultrastructurally. In the present study, we performed light and electron microscopic immunohistochemistry in conjunction with conventional transmission electron microscopy to assess the nature of involucrin involvement in normal and psoriatic CE. In normal epidermis, CEs were observed from the deepest cornified cells or, when present, from the transitional cells, increasing in thickness and changing electron densities with maturation. In psoriatic epidermis, CE formation started earlier, one to several cells below the cornified layer. Psoriatic CEs were generally thinner and showed a constant high electron density. Immunoelectron microscopy revealed that the normal CE was involucrin positive only at a very early stage, whereas psoriatic CE showed persistent involucrin immunoreactivity. These results suggest that in normal skin, involucrin is the major constituent of the CE only in its early stages of assembly. In contrast, CE formation seems to be initiated prematurely in psoriatic skin, where involucrin remains the major constituent of the CE during maturation. PMID- 7861009 TI - Cutaneous permeability barrier disruption increases fatty acid synthetic enzyme activity in the epidermis of hairless mice. AB - Previous studies have shown that abrogation of the cutaneous permeability barrier stimulates epidermal fatty acid synthesis and that this increase is required for barrier repair. The purpose of the present study was to determine the enzymatic basis for this increase in synthesis. Acute barrier disruption by tape stripping increased both acetyl CoA carboxylase (62%) and fatty acid synthase (54%) activities in the epidermis. Similarly, acute disruption of the barrier by topical acetone treatment increased epidermal acetyl CoA carboxylase (69%) and fatty acid synthase (43%) activities. In both acute models, provision of an artificial barrier by occlusion with an impermeable membrane prevented the increase in acetyl CoA carboxylase and fatty acid synthase activities, indicating that the increased activity was dependent on an increase in transepidermal water loss and cannot be attributed to nonspecific effects. In addition, chronic disruption of the barrier, produced by feeding an essential-fatty-acid-deficient diet, also increased acetyl CoA carboxylase (127%) and fatty acid synthase (49%) activities in the epidermis. Again, occlusion with an impermeable membrane decreased both acetyl CoA carboxylase and fatty acid synthase activities toward normal. These results indicate that the increase in fatty acid synthesis that occurs in the epidermis after barrier disruption is due to a coordinate increase in the activities of both epidermal acetyl CoA carboxylase and fatty acid synthase. PMID- 7861010 TI - Loricrin expression is coordinated with other epidermal proteins and the appearance of lipid lamellar granules in development. AB - In mouse, epidermal development proceeds from a single basal cell layer covered by a specialized single cell layer called the periderm at E14 to a fully differentiated stratified squamous epithelium at E18. To determine when loricrin, a major cell envelope component, is expressed during development, we examined fetal skin from mice of gestational ages E13 through E19 and compared the temporal pattern of loricrin expression with that of other differentiation markers. We found that loricrin mRNA and protein were expressed by E16, following the expression of keratins K1 and K10 and preceding the expression of profilaggrin. Interestingly, both loricrin and profilaggrin were initially expressed focally in areas corresponding to more advanced morphologic stages of maturation. Because the cornified envelope is a composite structure consisting of both protein and lipid components, we also monitored the appearance of lipid lamellar granules during epidermal development. These granules were first evident at E16 and the extrusion of lipids from the granules into the intercellular space occurred at E17, prior to the cross linking of loricrin into the cell envelope. Our results document that loricrin is expressed and accumulates at the cell periphery subsequent to the extrusion of lipids, but prior to processing of profilaggrin. We suggest that the sequential regulation of these events is critical for formation of epidermal barrier function during development. PMID- 7861011 TI - Osmium tetroxide and ruthenium tetroxide are complementary reagents for the preparation of epidermal samples for transmission electron microscopy. AB - Ruthenium tetroxide and osmium tetroxide were compared as post-fixatives in the preparation of human epidermis for transmission electron microscopic examination. Both reagents revealed characteristic lamellar granules within the granular layer and extruded lamellar granule contents in the upper granular layer. The transformation of the granule contents into multilamellar sheets at the interface between the granular and cornified layers and the persistence of these sheets through all levels of the stratum corneum were demonstrated only with ruthenium tetroxide fixation. Therefore, the reactivity of osmium tetroxide with isolated epidermal lipids was examined. The failure of osmium tetroxide to reveal membrane structures in the stratum corneum can be explained by its inability to react with many of the lipid components of these membranes, rather than to selective removal of lipids during tissue processing, as was formerly believed. Ruthenium tetroxide, a stronger oxidizing agent than osmium tetroxide, overcomes this problem but has other severe limitations as a post-fixative. PMID- 7861012 TI - A single parameter, oxygenated hemoglobin, can be used to quantify experimental irritant-induced inflammation. AB - To quantify the dose-response relation of irritant-induced erythema, we examined inflammation in human skin after application of an irritant, using perpendicular polarized photography and diffuse reflectance spectroscopy as compared to clinical visual scoring. The ventral forearms of 11 healthy subjects were patch tested for 24 h under occlusion in finn chambers with five concentrations of the irritant sodium lauryl sulfate. The tested sites and three control sites were evaluated clinically for erythema at 24, 48, and 72 h after occlusion, photographed using standard and perpendicular polarized photography, and measured by diffuse reflectance spectroscopy. All photographs were evaluated for erythema by three investigators. Diffuse reflectance spectra were analyzed, and changes in apparent oxyhemoglobin and deoxyhemoglobin concentrations were estimated. Clinical and photographic assessments of erythema yielded similar linear dose response relations. A linear dose-response relation, with no minimum threshold, also was obtained for changes in the apparent oxyhemoglobin concentration with increasing irritant dose, whereas the apparent deoxyhemoglobin concentrations were unchanged with increasing dose. These results show that diffuse reflectance spectroscopy permits the characterization of irritant-induced inflammation in terms of a single parameter, the apparent concentration of oxyhemoglobin, and that irritant-induced inflammation primarily involves the capillaries and the superficial arterial plexus. PMID- 7861013 TI - Identification of a homozygous exon-skipping mutation in the LAMC2 gene in a patient with Herlitz's junctional epidermolysis bullosa. AB - We describe a family with the Herlitz type of junctional epidermolysis bullosa, in which the disease is associated with a homozygous splice-site mutation in the gamma 2-chain gene (LAMC2) of laminin-5. The mutation consists of a G-to-T substitution resulting in the out-of-frame skipping of exon 7, a frame shift, and premature stop codon accompanied by a severe reduction in the level of mRNA from the mutant allele. The distribution of the wild-type and mutated gamma 2-chain alleles in family members implicates the mutation in the pathology and confirms the haplotypes of the healthy carriers previously determined by genetic linkage analysis. Our results confirm that the lethal Herlitz junctional epidermolysis bullosa phenotype is caused by mutations resulting in an altered synthesis of laminin-5. PMID- 7861014 TI - A glycine-to-arginine substitution in the triple-helical domain of type VII collagen in a family with dominant dystrophic epidermolysis bullosa. AB - We recently demonstrated strong genetic linkage between the type VII collagen gene (COL7A1) and both the dominant and recessive forms of dystrophic epidermolysis bullosa. In this study, we searched for mutations in dominant dystrophic epidermolysis bullosa using polymerase chain reaction amplification of segments of COL7A1, followed by heteroduplex analysis. Examination of the polymerase chain reaction corresponding to exon 73 revealed a heteroduplex resulting from a G-to-A transition at nucleotide 6127 in the triple-helical domain of COL7A1, which converted a glycine residue to an arginine (G2043R). The dominant dystrophic epidermolysis bullosa phenotype in this family probably arose because of a dominant negative effect of this mutation in COL7A1, resulting in the formation of structurally abnormal anchoring fibrils. PMID- 7861015 TI - Biologic effects and safety of stavudine: overview of phase I and II clinical trials. AB - Data on the biologic effects and safety of stavudine in patients with AIDS and AIDS-related complex represent results of two phase I trials (n = 84), another phase I study of patients with hematologic intolerance to zidovudine (n = 23), and a phase II trial (n = 152). The daily doses of stavudine ranged from 0.1 to 12.0 mg/kg. Increases in CD4 cell count, declines in serum p24 antigen, and weight gain were all related to the dose of stavudine. Doses of < or = 2 mg/kg/day (n = 216) were well-tolerated, with a median duration of therapy of > or = 48 weeks in the phase I studies and > or = 79 weeks in the phase II study. The predominant dose-limiting toxicity was peripheral neuropathy, which was related to both the dose and duration of treatment with stavudine. Elevations of liver enzymes were seen in some patients but appeared to be related to underlying disease rather than treatment. There was no evidence of dose-related hematologic toxicity. PMID- 7861016 TI - Design and implementation of the stavudine parallel-track program. AB - In a randomized, double-blind, large, simple trial, the safety and efficacy of two weight-adjusted dose levels of stavudine were evaluated in patients with advanced human immunodeficiency virus (HIV) infection. All patients were refractory to or intolerant of both zidovudine and didanosine. Patients weighing > or = 60 kg received 20 or 40 mg of stavudine twice daily. The dose was reduced to 15 or 30 mg for patients weighing 40-59 kg and to 10 or 20 mg for those weighing < 40 kg. The primary efficacy end points were survival and time to clinical progression of HIV disease. The primary safety end point was time to dose-limiting neuropathy. A total of 8127 patients were enrolled as of 31 July 1993. Although many patients who might have benefitted from stavudine were reached by the parallel-track program, a review of demographic data revealed disproportionate representation by white men from large metropolitan areas on both coasts. PMID- 7861017 TI - Stavudine in patients with AIDS and AIDS-related complex: AIDS clinical trials group 089. AB - In a phase I trial of stavudine in AIDS or AIDS-related complex (ARC), antiviral effects and safety were assessed in 41 patients treated with dosages of 0.5-12.0 mg/kg/day. Among evaluable patients, 10% increases in CD4 lymphocyte counts were sustained in 24 (60%) of 40 during treatment; an NAUC response (normalized area under the CD4 cell count-versus-time curve > 1.0) was observed in 31 (91%) of 34 at 10 weeks and in 20 (80%) of 25 at 24 weeks; 15 (83%) of 18 had decreases in p24 antigenemia; and 24 (60%) of 40 gained > or = 2.5 kg body weight. Median CD4 lymphocyte levels remained above baseline for 6 months in patients receiving > 0.5 mg/kg/day. Median serum p24 antigen levels remained below baseline for > or = 1 year in patients with p24 antigen responses. The principal toxicity was peripheral neuropathy, which generally resolved after drug discontinuation but limited the dosage to < or = 2.0 mg/kg/day. Additional trials assessing the effect of stavudine on overall morbidity and mortality are ongoing. PMID- 7861018 TI - Dose-related activity of stavudine in patients infected with human immunodeficiency virus. AB - In a multicenter, randomized, open-label, dose-ranging study to determine the relative effects of three dose levels of stavudine on CD4 lymphocyte count, weight gain, and hematologic variables in patients infected with human immunodeficiency virus (HIV), 152 patients with CD4 lymphocyte counts < or = 600/mm3 received stavudine at 0.1 mg/kg/day (n = 51), 0.5 mg/kg/day (n = 53), or 2.0 mg/kg/day (n = 48). The study was designed to evaluate the activity of stavudine after 10 weeks of therapy and permitted extended dosing and follow-up for long-term safety. A significant dose effect on increases in CD4 lymphocyte counts and declines in HIV titer in peripheral blood mononuclear cells was observed. Stavudine was well-tolerated; the only dose-related, dose-limiting adverse event was peripheral neuropathy, which usually was reversible. In this trial, the most favorable therapeutic index was seen at 0.5 mg/kg/day. PMID- 7861019 TI - Nucleoside reverse transcriptase inhibitors and resistance of human immunodeficiency virus type 1. AB - Drug-resistant isolates of human immunodeficiency virus type 1 (HIV-1) emerge during long-term treatment with nucleoside reverse transcriptase inhibitors, such as zidovudine. The clinical significance of in vitro drug resistance to zidovudine has been difficult to determine. However, in a virologic analysis of baseline specimens from the AIDS Clinical Trials Group (ACTG) 116B/117 study, high-level zidovudine resistance, defined as an IC50 of > or = 1 microM at study entry, was significantly associated with clinical disease progression. High-level zidovudine resistance also was an independent predictor of death as an end point, although this finding does not imply a direct causal effect. Duration and cumulative dose of prior zidovudine therapy did not predict clinical disease progression. More potent antiretroviral agents are needed that can be used in combination to achieve more complete virus suppression and to reduce the selection of drug-resistant HIV-1 mutants. PMID- 7861020 TI - The need for additional options in the treatment of human immunodeficiency virus infection. AB - Current therapy for human immunodeficiency virus (HIV) infection is inadequate to control the progression of the disease. Although existing nucleoside analogues, such as zidovudine, have clear benefits, they also have drawbacks, including toxicity and the possibility of drug resistance. In addition, the timing of therapy and the use of monotherapy versus combination therapy as initial treatment have not been definitively established. HIV drugs currently in development include newer nucleoside analogues, such as stavudine and lamivudine, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors. The addition of these agents to the antiretroviral armamentarium will expand the treatment options available to clinicians who treat patients with HIV infection. PMID- 7861021 TI - Treatment Trends in Human Immunodeficiency Virus Disease. Proceedings. San Francisco, California, 16 July 1993. PMID- 7861022 TI - Clinical aspects of human immunodeficiency virus disease: clinical rationale for treatment. AB - Guidelines regarding the use of antiretroviral therapy in adult patients infected with human immunodeficiency virus have been based primarily on the results of 15 major clinical trials in which patients have been categorized according to CD4 cell counts, symptoms, prior therapy, and conditions. In patients with limited treatment experience and advanced disease, zidovudine monotherapy is associated with improved survival, whereas only a transient delay in progression of disease is observed in patients with > 200 CD4 cells/mm3. Adding zalcitabine to the treatment regimen of zidovudine-experienced patients with advanced disease has not been demonstrated to be of clinical benefit, whereas switching these patients to didanosine may delay disease progression. The effect of any antiretroviral therapy in zidovudine-experienced patients with < 50 CD4 cells/mm3 remains indeterminate. The perinatal transmission rate can be reduced by as much as two thirds when zidovudine is administered to women after the first trimester. PMID- 7861023 TI - Comparison of metabolism and in vitro antiviral activity of stavudine versus other 2',3'-dideoxynucleoside analogues. AB - 2',3'-dideoxynucleosides are the principal drugs used to treat AIDS and are the only drugs thus far with demonstrated clinical benefits in patients with human immunodeficiency virus (HIV) infection. Although nucleoside analogues are structurally similar and have common mechanisms of action, each drug has unique molecular, cellular, and clinical features. For example, 3'-azido-3' deoxythymidine (zidovudine) and 3'-deoxy-2',3'-didehydrothymidine (stavudine) have similar in vitro anti-HIV activity but differ in their tendency to produce bone marrow suppression. Stavudine has been shown to be less myelosuppressive than zidovudine. With the exception of zidovudine, most of the clinically evaluated nucleoside analogues, including 2',3'-dideoxyinosine (didanosine), 2',3'-dideoxycytidine (zalcitabine), and stavudine, produce dose-dependent peripheral neuropathy. However, recent studies suggest that neuropathy induced by stavudine may be mediated by mechanisms different from those of didanosine and zalcitabine. PMID- 7861024 TI - Effect of the combination of interferon-alpha and stavudine on Friend virus infections in (B10.A x A.By)F1 mice. AB - The anti-Friend leukemia virus (FLV) effects of interferon-alpha-A/D (IFN-alpha) and 2',3'-didehydro-2',3'-dideoxythymidine (stavudine) used alone and in combination were examined in Mus dunni cells using a checkerboard-type experiment design. Strong antiviral synergy and a suggested cytotoxic synergy were seen. In two experiments to evaluate the effect of combining therapy with IFN-alpha and stavudine against FLV disease in the hybrid mouse strain (B10.A x A.By)F1, which is a strong producer of cytotoxic T cells, the drug combination resulted in better inhibition of FLV disease than did either drug used alone. Combination therapy inhibited splenomegaly, splenic virus infectious centers, plasma virus, and the virus-induced increase in hematocrit to a greater degree than did either drug alone. These data indicate that combination therapy with stavudine and IFN alpha is effective in the treatment of murine retrovirus infections and may be of value in the treatment of human AIDS. PMID- 7861025 TI - Clinical pharmacokinetics of nucleoside antiretroviral agents. AB - The rapid clinical evaluation of new drugs active against human immunodeficiency virus (HIV) requires that pharmacologic properties be carefully considered to determine optimal exposure profiles in patients. The published pharmacokinetic data for the nucleoside antiretroviral agents zidovudine, didanosine, zalcitabine, stavudine, and lamivudine show that administration of fixed doses of certain agents results in a considerable degree of between-patient variability in in vivo drug exposure. Pharmacologic treatment of HIV infection requires development of strategies for individualized adjustment of doses of certain agents with a high degree of interpatient variability. PMID- 7861026 TI - The type I interferon system is locally activated in psoriatic lesions. AB - The expression of mRNAs encoding interferons (IFNs) and IFN-inducible proteins has been studied in psoriatic lesions and in noninvolved skin. The specific mRNAs have been detected by in situ hybridization using antisense RNAs. Signals for the expression of IFN-gamma mRNA have been found exclusively in cells of psoriatic lesions, and most likely represent a subpopulation of infiltrating leukocytes. Weak signals of IFN-alpha mRNA have been detected throughout the hyperkeratotic epidermis, although specific signals for IFN-beta mRNA expression were not detectable. The expression of two IFN-alpha-inducible gene products, namely the MxA protein and the 2'-5' oligoadenylate (2-5A) synthetase, have been studied as markers for the local activation of the IFN-alpha system. Expression of MxA mRNA and protein was observed in psoriatic keratinocytes, but not in normal appearing keratinocytes adjacent to the lesions. Similarly, 2-5A synthetase expression was markedly elevated in psoriatic keratinocytes. The results of the present study indicate that the IFN-alpha system is selectively activated in psoriatic lesions, although it remains silent in noninvolved skin. The implications of this finding are discussed within the boundaries of current understanding of the cytokine network. PMID- 7861027 TI - Interferon expression in Crohn's disease patients: increased interferon-gamma and -alpha mRNA in the intestinal lamina propria mononuclear cells. AB - The in vivo interferon (IFN) activation in Crohn's disease was evaluated by measuring the relative amounts of IFN-alpha and -gamma mRNA in freshly isolated human lamina propria mononuclear cells (LPMC) from patients with Crohn's disease and controls. Both IFN-gamma and IFN-alpha mRNA, as estimated by dot blot analysis, were increased in Crohn's disease (LPMC), although the relative amounts of IFN mRNA appeared to differ among patients. Appreciable amounts of IFN-gamma mRNA were found in Crohn's disease peripheral blood mononuclear cells (PBMC) extracts, whereas the same cells were negative for IFN-alpha mRNA. Only minute amounts of IFN-gamma RNA were found sporadically in control LPMC while no IFN alpha was detected. Control PBMC were shown to be virtually negative for both IFN alpha and IFN-gamma mRNA. These data suggest that IFN induction in the normal human gut is a well-controlled function and that in Crohn's disease tissues, both IFN-gamma and IFN-alpha production are dysregulated. The increased IFN activity may represent a major feature in the induction and perpetuation of the chronic inflammatory process in Crohn's disease. PMID- 7861028 TI - Induction in interferon-alpha/beta-treated hepatocytes of the inhibitor of the multiplication of IFN-alpha/beta-resistant Friend leukemia cells. AB - We reported previously that interferon-alpha/beta (IFN-alpha/beta)-treated hepatocytes in culture released a soluble factor(s) that suppressed the multiplication of an INF-alpha/beta-resistant clone of Friend leukemia cells (FLCs). To characterize the factor(s) further, we first examined the possibility that products of nonparenchymal cells (NPCs) included in small number in the hepatocyte cultures were involved in the inhibitory activity. We prepared cultures of purified adherent NPCs, mostly Kupffer cells, and sinusoidal endothelial cells, and culture supernatants of NPCs pretreated with IFN alpha/beta were tested for the inhibitory activity for FLC multiplication. IFN did not induce any inhibitory activity in NPC cultures, whereas LPS-stimulated NPCs cultivated in parallel released several inhibitory factors including tumor necrosis factor-alpha (TNF-alpha). To explore the possibility that IFN augmented the release of hepatocyte cytosolic proteins, including arginase, we compared the inhibitory activity in culture supernatant of IFN-treated hepatocytes with that found in hepatocyte extract by anion-exchange chromatography. The IFN-induced inhibitory activity was eluted at relatively high salt concentration as a single peak, while the inhibitory activity in hepatocyte extract was co-eluted with arginase at low salt concentration. These results suggested that IFN induced production by hepatocytes of an inhibitor of FLC multiplication. PMID- 7861029 TI - Effects of anti-interferon-gamma and anti-interleukin-6 antibodies in disease models in mice: antibodies as carriers of cytokines. PMID- 7861030 TI - Mycobacterium bovis infection of mice lacking receptors for interferon-gamma or for transcription factor IRF-1. PMID- 7861031 TI - Soluble interferon-gamma receptor: a therapeutically useful drug for systemic lupus erythematosus. PMID- 7861032 TI - Antibody to the human interferon-alpha receptor reduces the loss of CD4+ T cells in macaques infected with the simian immunodeficiency virus, SIVmac. PMID- 7861033 TI - Interferon-alpha as an antagonist to proinflammatory and hematopoietic cytokines. PMID- 7861034 TI - Ketotifen inhibits tumor necrosis factor alpha production in the peripheral blood mononuclear cells of patients infected with human immunodeficiency virus. PMID- 7861035 TI - Pentoxifylline inhibits tumor necrosis factor production in septic shock. PMID- 7861036 TI - Interleukin-6 antibodies in rheumatoid arthritis. PMID- 7861037 TI - Use of anti-tumor necrosis factor antibodies in rheumatoid arthritis. PMID- 7861038 TI - Pharmacokinetics of interleukin-6 during therapy with anti-interleukin-6 monoclonal antibodies: enhanced clearance of interleukin-6 by a combination of three anti-interleukin-6 antibodies. PMID- 7861039 TI - Skin wound healing: transforming growth factor beta antagonists decrease scarring and improve quality. PMID- 7861040 TI - Interleukin-1 receptor antagonist and genetic susceptibility to inflammation. PMID- 7861041 TI - Interleukin-1 antagonists. PMID- 7861042 TI - Human monoclonal antibody as an interleukin-10-specific antagonist. PMID- 7861043 TI - Morphology of cystic structures seen in leprosy biopsy suspensions kept at cooler temperatures. AB - Cystic structures were seen in good numbers in biopsy suspensions obtained from leprosy patients and kept at cooler temperature. The structures were found arranged in singles, clusters or straight lines. In clusters, small round structures were seen surrounding a large spherical body. The small cystic bodies appeared empty, the medium sized bodies showed fine particles while the large ones showed spherules in and around them. It appears that the seed structure of the cycle emerges from the large spherical bodies. PMID- 7861044 TI - Disability grading in leprosy: current status. AB - The systems of classification and grading of disabilities in leprosy patients, suggested by WHO and others are reviewed. Taking into account the drawbacks observed in these classifications, a new system of grading of disabilities of hands and feet of leprosy patients based on the 1960 WHO classification is proposed for use in institutions. PMID- 7861045 TI - Anticardiolipin antibodies in leprosy. AB - Eighty-four leprosy patients were studied clinically and for IgG and IgM anticardiolipin (aCL) antibodies. Following WHO criteria, 41 patients could be classified as multibacillary (MB) and 43 as paucibacillary (PB). Baseline levels of IgG and IgM antibodies were 27 +/- 4.8 GPL and 20 +/- 3.4 MPL per ml respectively. Comparing with these, 60.9% of MB and 39.5% of PB cases showed rise in IgG and IgM anticardiolipin antibodies; 19.5% of MB and 4.6% of PB sera showed rise in only IgG antibodies, while 4.8% of MB and 13.9% of PB cases showed rise only in IgM antibodies. Rise in aCL antibodies had no correlation with cardiovascular involvement, bacteriological index, reactive state and duration or regularity of treatment. PMID- 7861046 TI - Evaluation of modified lepro-agglutination as screening test for leprosy. AB - One hundred thirty-three leprosy sera (83 multibacillary (MB) and 50 paucibacillary (PB) cases) were screened by lepro-agglutination (LA) and M.leprae particle agglutination (MLPA) tests. Larger number of MB sera were positive by LA (86.75%) than by MLPA (45.12%) test. Thirty-seven of the 45 MB sera negative by MLPA test were positive by LA test. The reverse was true in three out of 11 MB sera. PB sera showed positivity of 16% in LA test and 24% in MLPA test. All the 55 sera from normal healthy individuals and 18 VDRL positive sera from syphilis patients were found to be negative by LA test. PMID- 7861047 TI - Cancer associated with leprosy. AB - Eighty-seven leprosy patients with cancer, seen between 1960 to 1984, were studied. Cancer in patients with leprosy occurred in a younger age group compared to the general population. The most common type of malignancy seen among males was squamous cell carcinoma of the lower extremity while in hospital patient population it was cancer of head and neck. Among the females, carcinoma cervix was the most common as in the hospital patients. The types of malignancy occurring among leprosy patients was similar to that of the hospital patient population with the exception of an increase in incidence of squamous cell carcinoma of extremities. PMID- 7861048 TI - Changing horizon of rehabilitation. PMID- 7861049 TI - Psychiatric morbidity in displaced leprosy patients. AB - One hundred confirmed leprosy patients, all of them migrated from elsewhere, were examined for psychiatric co-morbidity. Forty-six of them were from an 'ashram' and the others were from a slum area. 76% of the patients were found to be having psychiatric illness. Of these, 55% were having neurotic depression and 21% had anxiety neurosis. Single, unemployed, socio-economically backward and patients with physical deformities were suffering significantly more often with psychiatric symptoms. Psychiatric morbidity was found to be more frequent in the patients staying in slum than in those in the 'ashram' where they had some security. PMID- 7861050 TI - Task-oriented training of primary health care personnel in leprosy case detection -an assessment. PMID- 7861051 TI - [Diagnosis of perioperative myocardial infarction by cardiac troponin T following coronary artery bypass grafting]. AB - The determinations of cardiac troponin T provide the highest diagnostic efficiency for the detection of myocardial cell necrosis. To assess perioperative myocardial infarction, serum levels of cardiac troponin T were determined in 14 patients undergoing coronary artery bypass grafting (CABG). The patients were divided into two groups: group I (n = 9), those whose troponin T was less than 1.00 ng/ml on the first postoperative day; group II (n = 5), those whose troponin T was more than 1.00 ng/ml on the first postoperative day. Troponin T levels in group II patients were significantly higher than in group I from the second to the seventh postoperative day. Two patients in group II had specific changes on the electrocardiogram detecting perioperative myocardial infarction as a new Q wave and R wave reduction. These results suggest that troponin T is a valuable marker of perioperative myocardial infarction following CABG. PMID- 7861052 TI - [Quantitative hemodynamic assessment of internal thoracic artery grafts using transthoracic duplex imaging]. AB - The hemodynamics of blood flow in internal thoracic artery (ITA) grafts were studied using transthoracic duplex imaging prior to and following coronary artery bypass grafting (CABG) in 37 patients. Transthoracic images of the ITA were obtained through the first intercostal space using a 7.5 MHz probe, and their diameter and area were measured by B-mode imaging. Systolic, diastolic, mean and end-diastolic blood flow velocity (Vs, Vd, Vm, and Ved) were determined based on Doppler signals and systolic, diastolic, and total blood flow (Fs, Fd, and Ftotal) were calculated by the following formula: Flow = Vm x area x 60/10(3). The diameter of the ITA increased following CABG. Prior to CABG, Vs, and Fs, were dominant, while following CABG, the hemodynamic pattern was diastolic dominant, although individual variation existed. The ITA blood flow was measured in 4 groups, in patients who had had a previous anterior myocardial infarction and no redistribution on myocardial scintigraphy (group I), in patients with 99-100% coronary artery stenosis who had not had an anterior myocardial infarction or who had an anterior myocardial infarction and had redistribution (group IIa), in patients with the same criteria as group IIa but who had 90% coronary stenosis (group IIb), and in patients with 75% coronary stenosis who had not had anterior myocardial infarction (group IIc). Blood flow was 57, 73, 44mL and 34 mL/min, and the percentage of diastolic flow was 72, 69, 61, 59% respectively. These results show that ITA blood flow competes with native coronary artery flow in patients with moderate coronary stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861053 TI - [Myocardial preservation by continuous perfusion of Krebs-Henseleit solution--the temperature dependency of the optimal perfusion pressure]. AB - The aim of this study was to determine the temperature dependency of the optimal pressure in myocardial preservation by continuous perfusion with Krebs-Henseleit bicarbonate buffer (KHBB) solution. Hearts from Wistar male rats were perfused with KHBB solution and cardiac function (aortic flow) was measured using an isolated working rat heart preparation. In the preliminary experiment, hearts were then preserved using Langendorff perfusion with KHBB solution of 37, 20 or 4 degrees C for 2 hours at a perfusion pressure of 100 cmH2O. This was followed by 15 min of Langendorff perfusion (37 degrees C, 100 cmH2O) and 20 min working perfusion. The 37 degrees C group and 20 degrees C group exhibited better functional recoveries of aortic flow (%AF) in the post-preservation period compared to the 4 degrees C group. In the test experiment, hearts were preserved using Langendorff perfusion for 4 hours at 37 degrees C or for 8 hours at 20 degrees C at various perfusion pressures. At 37 degrees C, %AF after 4 hours of the preservation were 64.7 +/- 2.6, 69.0 +/- 3.2, 81.9 +/- 3.1, 94.7 +/- 3.3 and 63.5 +/- 4.0% (p < 0.05 vs the 100 cmH2O group) at the perfusion pressure of 100, 60, 20, 15 and 10 cmH2O, respectively. %AF after 8 hours of the preservation at 15 cmH2O was 56.3 +/- 2.5%. At 20 degrees C, %AF after 8 hours of the preservatin was 78.9 +/- 3.3, 81.9 +/- 2.3, 67.4 +/- 1.9 and 65.9 +/- 2.2% (p < 0.05 vs the 60 cmH2O group) at the perfusion pressure of 60, 30, 10 and 15 cmH2O, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861054 TI - [Free arterial graft for coronary bypass grafting]. AB - Free arterial grafts were aggressively placed in 39 patients (1991 to 1993). There were 34 males and 5 females, and mean age was 59.9 year old. Of 85 arterial grafts, 41 were free grafts, and their materials included left and right internal thoracic artery (LITA, RITA) and right gastroepiploic artery (GEA). There were one free LITA-left anterior descending coronary artery (LAD), seven free RITA LAD, three free RITA-diagonal branch (Dx), 14 free RITA-left circumflex coronary artery (LCX), 10 free RITA-right coronary artery (RCA), two sequential RITA-Dx LCX, one free GEA-Dx, two free GEA-LCX, and one free GEA-RCA bypass. Of 41 free arterial grafts, 38 were in the aorta-coronary position, and the proximal anastomosis was constructed first under single aortic cross-clamping to get the larger anastomotic sites for both at the proximal and distal ends of the arterial graft. The proximal sites of the remaining 3 arterial grafts were placed to concomitantly utilized saphenous vein grafts in two patients and RCA in one patient because of their shortness. Perioperative complications included no exploration for bleeding, myocardial infarction in one (2.6%), intra-aortic balloon pumping in three (7.7%), and wound complications in two (5.1%). 28 cases (72%) were completely revascularized with only arterial grafts. Of 41 free arterial grafts studied within one month after operation, all grafts were patent. All patients were free from angina after a 27 months mean follow-up. We believe that the proximal anastomosis technique for free arterial graft we used could be acceptable alternative for many surgeons. These excellent results justify wider use of free arterial grafts. PMID- 7861055 TI - [An autopsy study of the mode of cancer metastasis on the esophagectomied patients for esophageal cancer]. AB - The records of autopsy on 43 patients underwent esophagectomy were evaluated retrospectively. Fifteen patients were performed palliative surgical treatment and 28 were curative, there were 41 men and 2 women in the series. The mean age at the first operation was 59.5 yr. The distribution of the primary lesions were 1 cervical, 40 thoracic (3 upper intra-thoracic, 28 middle intra-thoracic and 9 lower intra-thoracic) and 2 abdominal esophagus. There were 42 cases of squamous cell carcinoma (13 well differentiated types, 25 moderately differentiated types and 4 poorly differentiated types) and 1 adenosquamous cell carcinoma. Their stage classification were 0 for 2 patients, I for 1, III for 13 and IV for 27. In cases of palliative surgical treatment, the residual tumor were present on 6 cases in trachea or bronchus and 2 in aorta. Others were the rest of metastatic nodes in 3 cases, positive surgical margin in 3 and visceral metastasis and peritoneal dissemination in 1. At autopsy, 14 patients (93%) had distant organ metastases, 11 (73%) local recurrent tumor, 11 (73%) node metastases and 9 (60%) disseminations. In cases of curative surgical treatment, the first recurrent sites were as follows. Lymph node metastasis observed in 20 cases (71%), local recurrence in 9 cases (32%), distant organ metastases in 8 cases (28%) and disseminations in 5 cases (18%). While at autopsy, 24 patients (86%) had lymph node metastases, 20 (71%) distant organ metastases, 15 (54%) local recurrent tumors and 11 (39%) disseminations. On 10 cases whose first recurrent site was observed only at lymph node, 9 cases (90%) had distant organ metastases at autopsy. In both cases of palliative surgical treatment and of curative surgical treatment, the most dominant metastatic site at autopsy was distant organ metastasis. Therefore, in the future, distant organ metastasis must be an important target for esophageal cancer treatment. PMID- 7861056 TI - [Measurement of cytokines at cardiopulmonary-bypass]. AB - Tumor Necrosis Factor alpha (TNF-alpha), Interleukin 1 beta (IL-1 beta), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and Granulocyte Elastaze (GEL) were measured in twenty-five patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB). These levels were measured before and immediately after CPB, on the first, the third, and the sixth operative days. According to results, TNF-alpha and IL-1 beta were detected only three of the twenty-five patients with CPB more than 250 minutes. The IL-6 level that was 29.93 +/- 6.73 pg/ml before CPB peaked at 1417.81 +/- 149.81 pg/ml immediately after CPB. IL-8 (2.92 +/- 1.65 pg/ml) peaked at 36.73 +/- 35.52 pg/ml (p < 0.01) after immediately CPB. There were statistically significant differences in the IL-6 and IL-8 between levels before and immediately after CPB (p < 0.01). The GEL level increased from 181.41 +/- 128.98 micrograms/L before CPB to 2182.57 +/- 1757.25 micrograms/L immediately after CPB, with significant difference (p < 0.01). IL-6 and IL-8 levels correlated significantly with the time of CPB (r = 0.612, p < 0.01, r = 0.707, p < 0.001, respectively). In addition, the GEL levels significantly correlated with IL-8 level at each time of CPB (r = 0.733, p < 0.001). This study demonstrated that measurements of cytokines are good indicators of tissue damage for cardiac surgery and also indicates cytopathogenicity of IL-8 is due to GEL. PMID- 7861057 TI - [Aortic valve replacement in patients older than 75 years of age]. AB - From 1988 to 1992, 16 patients older than 75 years underwent AVR (14 cases) or AVR+MVR (two cases). All patients were followed up for an average of 2.4 years after the operation and follow-up totaled to 38 patient-years. There were no hospital death and one late death. The survival rate was 93.8% through 1 to 5 years and 15 patients are now in NYHA class I or II. The problems of AVR for elderly patients were calcification and small annulus. Decalcification using CUSA was effective technique and supraannular fixing of bioprosthetic valve avoided from aortic annular enlargement. The improved quality of life after AVR supports the aggressive surgery in elderly population. PMID- 7861058 TI - [The changes on cerebral hemodynamics during selective cerebral perfusion cooling]. AB - We studied the influence on cerebral hemodynamics with 10 pigs, weighing 25 to 30 kg, when the temperature of perfusion blood changed in both rapid cooling and rewarming, and in slow them. As for the protocol of temperature, we decided that rapid change was the large temperature gradient of more than 0.5 degree C/min, and slow change was the small gradient of less than 0.3 degree C/min. Cardiopulmonary bypass (CPB) was established with a flow rate of 60 ml/kg/min, and core cooling was performed until the temperature of the returned blood from internal jugular vein reached 25 degrees C/min. For selective cerebral perfusion (SCP), blood was infused into aortic arch with the clamp of descending aorta at the temperature of less than 20 degrees C. We measured regional tissue cerebral blood flow (TCBF), intracranial pressure (ICP), carotid arterial flow (CAF), and carotid arterial pressure (CAP), and PCO2 in both CPB and SCP. Rapid cooling during CPB caused an elevation in CAP, and marked decrease in CAF, ICP, and PCO2. In contrast, rapid rewarming caused the significant increase in CAF, ICP. Slow change did not cause marked difference in CAP, CAF, and ICP, and PCO2. Moreover, TCBF was not significant in both rapid and slow changes. On the other hand, rapid change in SCP caused a significant decrease in CAP, significant difference in CAF, ICP. Slow change did not cause significant difference in them as same as in CPB. In conclusion, we presume that the influence on cerebral hemodynamics is less in slow cooling and rewarming than in rapid changes. PMID- 7861059 TI - [Preoperative assessment of aortic dissection by three-dimensional CT angiography]. AB - In 21 patients with aortic dissection including 12 patients with acute aortic dissection, aortic lesions were evaluated preoperatively by newly developed three dimensional CT angiography (3 D-CTA) using helical scan CT. Rapid and safe three dimensional evaluation of aortic dissection was achieved with no complications. Three-dimensional structure of aortic dissection was well reflected in the image of 3D-CTA. Preoperative three-dimensional evaluation was useful to determine and proceed the operative procedure for the repair of aortic dissection. All patients were alive and results of surgical treatments were excellent. Intimal flaps and entries were visualized by multiple threshold display (MTD) method of 3D-CTA. Multiple threshold display method is an important three-dimensional reconstructive method and 3D-CTA may be a new useful and powerful diagnostic modality for aortic dissection. PMID- 7861060 TI - [Influence of blood transfusion on cellular immunity after open heart surgery]. AB - The effect of blood transfusion on cellular immunity was evaluated by measuring T cell subsets in 22 adult patients after open heart surgery. The patients were divided into two groups according to whether or not they received blood transfusions. There were no significant differences in pump time or aortic cross clamp time between the two groups. Leukocytosis was evident in both groups after open heart surgery, but the percentage to lymphocytes was reduced. The number of T cells were also reduced in both two groups. In the group that did not receive blood, the number of T cells were reduced the first day after surgery, but returned to preoperative levels two days later. Those that received blood transfusions had persistently low T cell counts three days after the operation. CD4 positive T cells were reduced the first day after operation but returned to preoperative levels three days after the operation in both groups. The percentage of CD8 positive T cells were unchanged in the group that didn't have a blood transfusion. CD8 positive T cells were significantly reduced three days post operatively in the group that received blood transfusions. The cellular immunity was disturbed for an extended period in the patients that received blood transfusions. PMID- 7861061 TI - [Mitral annuloplasty for mitral regurgitation due to dilated cardiomyopathy--a case report]. AB - A 74-year-old woman who had had severe mitral regurgitation (MR) due to dilated cardiomyopathy (DCM) was referred to our hospital for surgical management because she had suffered from congestive heart failure (CHF) of NYHA functional class IV in spite of maximal medical treatment. We have successfully performed mitral annuloplasty (MAP) using a Carpentier annuloplasty ring. Her postoperative course was good and her symptom improved to NYHA functional class II to III one year after the operation. However, the left ventricular functional improvement was minimal. The regurgitant fraction decreased from 0.62 to 0.11 after the operation but the left ventricular ejection fraction also decreased from 0.26 to 0.11. We had an impression that MAP could be considered as one of the procedures for severe MR due to DCM, if CHF was not controlled by any medications. PMID- 7861062 TI - [Quadruple coronary artery bypass grafting with arterial grafts--application of internal thoracic artery and right gastroepiploic artery]. AB - Arterial graft has been widely applied for coronary artery bypass because of its excellent long-term patency. However, when more than four coronary bypass graftings should be carried out using internal thoracic arteries (ITAs) and right gastroepiploic artery (GEA), some surgical techniques must be devised. We performed quadruple coronary artery bypass grafting using three arterial grafts; bilateral ITAs and GEA, and obtained good results. We used free RITA graft for sequential grafting in one case. In another case, GEA was divided into two segments and used as two free grafts. From our experience, we believe it is possible to perform multiple coronary revascularization using only arterial grafts with one median skin incision. PMID- 7861063 TI - [A case of pulmonary malignant lymphoma associated with localized amyloid plaque]. AB - A 51-year-old woman admitted to our hospital. Chest X-ray film showed infiltrations in left S4 region, which had been pointed out since two years before. On exploratory thoracotomy, lingual segmentectomy was performed because no metastatic lesions were found in the mediastinal and hilar lymph nodes. Pathological and immunohistological examinations revealed findings corresponding to pulmonary malignant lymphoma (diffuse, small cell type, B cell) with amyloid plaque. The patient is doing well 20 months after operation without any signs of recurrence. The clinical and histological findings of this case may suggest a close relationship between malignant lymphoma and production of amyloid. PMID- 7861064 TI - [A successful repair of ventricular septal defect and patient ductus arteriosus associated with pulmonary hypertension in an infant with left lung agenesis]. AB - We report the first case of successful repair of ventricular septal defect (VSD) and patent ductus arteriosus (PDA) associated with pulmonary hypertension in an infant with left lung agenesis. A 70-days-old infant was referred to our hospital with the diagnosis of congenital heart disease and abnormalities of the left lung. Two-dimensional echocardiogram showed ventricular septal defect and patent ductus arteriosus associated with pulmonary hypertension. Computed tomogram of the chest and bronchogram confirmed agenesis of the left lung. The operation was performed at age 114 days with the body weight 4333 g. VSD was closed with the patch and PDA was ligated under cardiopulmonary bypass. Postoperative course was uneventful. Cardiac catheterization, 50 days after operation, revealed normal pulmonary arterial pressure and good cardiac function. Agenesis of the lung is a rare condition and often associated with congenital abnormalities of the skeletal, gastrointestinal, genitourinary and cardiovascular system. As the prognosis is poor especially in those with congenital heart disease, the cardiac surgery is mandatory for the patient to survive. PMID- 7861065 TI - [Coronary artery bypass grafting for active aortitis syndrome with bilateral coronary ostial stenosis]. AB - Coronary artery bypass grafting was performed on a 31-year-old female for treatment of active aortitis syndrome with unstable angina. Preoperative coronary angiography revealed ostial stenosis of coronary arteries. The ascending aorta was intensely inflamed. In the proximal anastomosis, the ascending aorta was sutured with an autogenous pericardial patch and anastomosed with the saphenous vein (SV) to be jointed to left anterior descending (LAD). At the same time, gastroepiploic artery (GEA) was connected to LAD by taking into account a degenerative change in remote stage. Right coronary artery was anastomosed with right internal thoracic artery (RITA). The postoperative course was satisfactory. On graft angiography SV and RITA were adequately patent, but GEA was unsatisfactorily patent because of its competition with SV for patency. This surgical procedure seemed to be an option to be indicated for a patient with unstable angina at an active inflammatory stage. PMID- 7861066 TI - [Two cases of surgically treated malignant primary tumors originated from the pulmonary artery]. AB - Two surgically treated cases of malignant tumors which originated inside of the pulmonary artery were reported. A 62-year-old female with an undifferentiated sarcoma and a 24-year-old male with a malignant fibrous histiocytoma were successively operated on in two months for the release of their chief complaints of exertional dyspnea. In the first case the tumor was resected completely, although partially resected in the second case. Preoperatively, noninvasive examinations including the echocardiography, the computed tomography and the magnetic resonance imaging confirmed the presence of these tumors in the main pulmonary arteries in both cases and also the invasion to the vessel wall with the growth to the pericardial cavity in the second case. Both patients are doing well and has been followed up at the out-patient department 22 and 20 months after surgery, respectively. PMID- 7861067 TI - [A case of successful surgical treatment for coarctation of the aorta associated with ruptured cerebral aneurysm]. AB - We present a case of a sixteen year old boy with coarctation of the aorta who suffered ruptured cerebral aneurysm. Both cerebral and aortic lesions were successfully corrected. He complained of sudden headache and nausea. Subarachnoid hemorrhage was diagnosed by computed tomography of the head. Cerebroangiography demonstrated coarctation of the aorta. Clipping of cerebral aneurysm was done at first, then three months later, complete resection of the aortic coarctation and artificial graft replacement was done by using femoral veno-arterial cardiopulmonary bypass. PMID- 7861068 TI - [Tetralogy of Fallot with absent pulmonary valve: a successful case by total corrective surgery in 25 days old infant]. AB - A 25 days old neonate of tetralogy of Fallot with absent pulmonary valve underwent total corrective surgery which consisted of VSD patch closure, resection of anterior wall of both pulmonary arteries and right ventricular outflow tract reconstruction using a monocuspid equine pericardial patch. Postoperatively, the right pulmonary artery diameter decreased from 17.8 mm (307%N) to 7.5 mm (129%N) and the left pulmonary artery diameter from 16.9 mm (338%N) to 8.3 mm (166%N). The patient was weaned from the ventilator 2 days after operation, whose post-operative course was uneventful. Total corrective surgery may provide a great success to symptomatic patients during the neonatal period. PMID- 7861069 TI - [A case report of disappearance of free internal thoracic artery graft stenosis]. AB - We have experienced an interesting case of spontaneous disappearance of stenosis of the injured free internal thoracic artery graft six months after coronary artery bypass grafting. A 61-year-old male underwent coronary bypass surgery with in situ left internal thoracic artery (LITA)-left anterior descending (LAD) and free right internal thoracic artery (RITA)-first diagonal branch (D1) bypass at our hospital. Postoperative angiogram showed the stenosis of the distal portion of the free RITA. We judged it was the injury by the electrocautery when dissecting the RITA. He was admitted to our hospital and received repeat angiography because of recurrence of angina six months after surgery. Repeat angiogram showed the good patency of LITA and complete disappearance of the stenosis of the free RITA. We consider that this case proved the free ITA can be a living graft. PMID- 7861070 TI - [Surgical repairs of anomalous pulmonary venous connection to superior vena cava and right atrial junction]. AB - We recently encountered a case of total anomalous pulmonary venous connection (TAPVC, Darling Ib) and 3 cases of partial anomalous pulmonary venous connections (PAPVC) to the superior vena cava. We surgically treated these 4 cases by different procedures which were selected according to the morphological features of individual cases. In the case of TAPVC (Darling Ib), we created a right atrial wall flap, according to the method of Vargas, so that the blood from the abnormal pulmonary vein could pass the left atrium via the superior vena cava and atrial septal defect. In 3 cases of PAPVC, we modified some techniques of right atrial incision and closure by suturing. Through these surgical procedures, none of the 4 patients developed postoperative stenosis of the pulmonary venous pathway or arrhythmias. Various surgical procedures have been reported for the treatment of anomalous pulmonary venous connection, an anomaly involving direct connection of the pulmonary vein to the superior vena cava or to the right atrial junction of the superior vena cava. However, the incidence of postoperative stenosis or obstruction of the pulmonary venous pathway or postoperative sick sinus syndrome has been high with these procedures. PMID- 7861071 TI - [Staged operation for aneurysm of the entire aorta: report of four cases]. AB - Between September 1989 and May 1994, 3 patients with aortic dissection and one with atherosclerotic total aortic aneurysm associated with annuloaortic ectasia underwent successful staged operation for aneurysm of the entire aorta and aortic regurgitation. A composite graft was used for total aortic root replacement. Carbrol and Piehler techniques, Carrel patch and saphenous vein grafting were employed for coronary artery reconstruction. En bloc arch reconstruction was performed in one patient and three vessels graft replacement in 3 patients under hypothermic separate cerebral perfusion. Combined antegrade with retrograde oxygenated crystalloid cardioplegia and terminal warm blood cardioplegia were used for myocardial protection during prolonged aortic cross clamping in a simultaneous total aortic root and arch replacement. Elephant trunk was used at the distal arch anastomosis in 3 patients and useful for following thoracoabdominal surgery. In 3 patients, separate perfusion of upper and lower body technique with moderate hypothermia was employed and seemed to be useful in the patients who require extensive thoracoabdominal replacement to prevent spinal cord injury. All patients had no major complications and have been well. PMID- 7861072 TI - [An adult case of bronchodilation using stents for right aortic arch]. AB - Airway obstruction due to oppression by the right aortic arch is relatively common in the newborn, but has never been reported in the adult. We reported an aged case of right main bronchial stenosis due to the oppression by the right aortic arch, performed successful bronchodilatation using the stent. A 92-year old male complained of fever and productive cough and hospitalized with a diagnosis of pneumonia. Close examinations revealed that his right main bronchus was stenotic due to oppression by the right aortic arch. Bronchodilatation was performed successfully using a Gianuturco-type expandable metallic stent. No endoluminal stenosis was found during 12 months follow up. For the treatment of bronchial deformity by the extrabronchial oppression, implantation of the Gianturco-type expandable metallic stent is considered to be very useful method. PMID- 7861073 TI - [A successful case of transaortic coronary patch angioplasty for left coronary ostial stenosis in a middle-aged woman]. AB - A 46-year-old woman was admitted to our hospital because of effort angina. Electrocardiogram on exercise showed a significant ST depression in I, II, III, aVF, and V3-6 201Thallium myocardial scintigram demonstrated a low uptake lesion on effort and redistribution in anterior wall of left ventricle. Coronary angiography showed a 50% stenosis only in the left coronary ostium. Operation was carried out by transaortic patch angioplasty using autologous pericardium fixed with 0.25% glutaraldehyde. Her postoperative course was uneventful. Anginal discomfort disappeared, and favorable results was obtained. Recent reports suggest that an isolated coronary ostial stenosis is a distinct clinical entity which is different from the usual atherosclerotic ischemic heart disease. The transaortic patch angioplasty might be useful operative method for the isolated coronary ostial stenosis. PMID- 7861074 TI - [A case of intractable pulmonary tuberculosis complicated by idiopathic thrombocytopenic purpura (ITP)]. AB - The authors describe a case of pulmonary tuberculosis with multiple drug resistance and complicated by severe idiopathic thrombocytopenic purpura (ITP). The patient was initially treated with high-dose gamma globulin therapy and splenectomy. These procedures resulted in improvement of the patient's condition; the platelet count increased from 7,000/mm3 to 230,000/mm3 and the bleeding time fell from 15 min to 1 min 30 s. Given the significant improvement in the patient's condition, it was considered safe to carry out left pulmonary upper lobectomy and thoracoplasty. There have been no reports describing pulmonary resection performed for inflammatory lung disease in patients with ITP. High-dose gamma globulin therapy rapidly brings about an increase in the platelet count and a reduction of the bleeding time, and it thus extremely useful as preoperative treatment in surgical cases complicated by thrombocytopenia. PMID- 7861075 TI - Surface morphology of middle ear epithelium in chronic ear disease. AB - The ultrastructural details of normal middle ear mucosa have been reported in detail in the literature. This study was aimed at investigating the superficial structure of middle ear epithelium with the scanning electron microscope in patients with persistent otitis media with effusion (OME) and chronic suppurative otitis media (CSOM), especially in the light of the authors' recent findings regarding decreased ciliary beat frequency (CBF) in patients exposed to tobacco smoke. Mucosal biopsies were taken from the anterior mesotympanum in four patients with OME and another four patients with CSOM. There was no significant abnormality of cellular surface structure in patients with chronic middle ear disease. Furthermore, no significant difference was observed between smoke exposed and nonsmoke exposed patients. It is concluded that the effect of tobacco smoke on CBF is functional and not related to any anatomical abnormality observed by scanning electron microscopy (SEM). PMID- 7861076 TI - A one-stage surgical procedure for placement of percutaneous implants for the bone-anchored hearing aid. AB - The bone-anchored hearing aid (BAHA) is an alternative to the conventional bone conduction hearing aid. The transducer is coupled to a percutaneous titanium implant which is traditionally inserted into the temporal bone in two stages. This study focusses on a one-stage surgical technique for the implantation of percutaneous implants. The preliminary clinical results of 33 one-stage implants in 33 patients are presented. Post-operative necrosis of the skin grafts did not occur. After a follow-up which varied from nine to 25 months, 31 out of the 33 fixtures (94 per cent) were anchored firmly in the skull. Twenty-six out of the 33 implants (79 per cent) remained free from potentially dangerous skin reactions. The results were statistically comparable to those obtained with two stage implants at the same clinic. Although longer follow-up is needed before a general statement can be made about replacing the two-stage technique, the preliminary one-stage results are promising. PMID- 7861077 TI - Lateral approaches to the median skull base through the petrous bone: the system of the modified transcochlear approach. AB - Twenty-three patients with intradural lesions of the petroclival region and prepontine cistern were managed in our centres by the modified transcochlear approach. Total tumour removal was accomplished in 17 patients, while a second stage was planned for the remaining six patients. Two cases died in the immediate post-operative period. All the remaining cases showed a good outcome and returned to work. The basic approach type A is further classified according to its anterior, superior and inferior extension into types B, C and D respectively. The surgical procedure, classification, illustrative case reports and patients' summaries are presented. PMID- 7861078 TI - The distribution of nasal airflow sensitivity in normal subjects. AB - Nasal airflow modifies the pattern of ventilation presumably due in part to nervous signals arising in the nose and transmitted along the trigeminal nerve to the respiratory centre. Nasal receptor tissue must also be important in determining the sensation of airflow at a conscious level but little attention has been paid to the distribution and function of these receptors. An experimental model to deliver a pulse of air at different velocities to various nasal test sites is described. In this way nasal sensitivity to an air jet can be mapped out. Sensitivity of the nose to an air jet is greatest at the entrance to the nose--the region of the nasal vestibule. PMID- 7861079 TI - Rhinosporidiosis: immunohistochemical and electron microscopic studies. AB - Sixteen biopsies of rhinosporidiosis (15 nasal and one conjunctival) from 16 Southern Indian male immigrant workers showed mucosal lymphoplasmacellular infiltrates together with transepithelial elimination of nodular bodies and destruction of some late stage nodular bodies in histiocytic granulomata with central neutrophilic microabscesses. Early nodular bodies were immunohistochemically positive for alpha 1-AT, alpha 1-ACT, CEA, S100, fibronectin, amyloid-p-component, IgG, IgA, C1q and C3. Electron microscopy showed organized concentric lamellated bodies in early nodular bodies and not in end-stage nodular bodies which contained mostly amorphous electron dense materials. Structures formerly regarded as 'sporangia' and 'spores' are believed to be lysosomal bodies loaded with indigestible residues to be cleared via transepithelial elimination or segregated/destroyed by secondary immune/granulomatous responses. PMID- 7861080 TI - The role of transcanine surgery in antrochoanal polyps. AB - During a period of two years, 24 cases of antrochoanal polyps were diagnosed by clinical examination, nasal endoscopy and computerized tomography. Surgery started with endoscopic transnasal removal of the polyp. Every attempt was made to remove the antral portion of the polyp through the wide ostium. Then transcanine sinuscopy was performed. Remnants of the polyp were detected and removed in five cases. One or more other cysts were found and extirpated in 11 cases. Endoscopic follow-up for 18 months to three years revealed no recurrence. It is recommended that endoscopic middle meatal surgery should be combined with transcanine sinuscopy to ensure complete removal of antrochoanal polyps. PMID- 7861081 TI - Mast cell ultrastructure in the adenoids of children with and without secretory otitis media. AB - This study was designed to compare the differences in morphology of the mast cells from the adenoid in children with otitis media with effusion (OME) and those from children with recurrent tonsillitis. Tissue for electron microscopy was prepared in the standard manner and between three and 10 blocks were examined for each child. All the mast cells with nuclei were photographed and the condition of the granules noted. The number of electron dense granules in each cell was assessed on a scale between zero and 10. Sixteen unselected children with OME were compared with 19 children with recurrent tonsillitis. There were no obvious differences in the degree of degranulation between the two groups although there was more vacuolation than previously described in the normal nose but less than in those patients with perennial allergic rhinitis. Allergy and mast cell reactions do not seem to predispose to OME. It was concluded that the adenoids are not the ideal tissue in which to study normal mast cells. PMID- 7861082 TI - Suspension microlaryngoscopic surgery and indirect microlaryngostroboscopic surgery for benign lesions of the vocal folds. AB - A prospective study was designed to compare the effects on voice capacities after either suspension microlaryngoscopic surgery or indirect microlaryngostroboscopic surgery. Patients where the clinical diagnosis 'dysphonia due to a benign lesion of the vocal fold' was made, and who could be operated in either way, entered the study. Post-operative voice evaluation was performed on 21 patients after suspension microlaryngoscopic or indirect microlaryngostroboscopic surgery. The long-term voice results following indirect microlaryngostroboscopic surgery and suspension microlaryngoscopic surgery demonstrate a statistically significant improvement for the maximum intensity, maximum dynamic intensity range, dynamic intensity range at habitual speaking pitch, and melodic pitch range. In selected cases indirect microlaryngostroboscopic surgery offers a very good functional result. PMID- 7861083 TI - Cervical node metastases presenting with features of branchial cysts. AB - For many years it has been recognized that seemingly benign neck cysts may contain carcinoma. The true incidence is unknown. This paper investigated nine out of 270 patients presenting with a neck mass--which proved to contain a squamous carcinoma. Records (from a 30-year period) of over 3400 patients with squamous carcinoma of the head and neck, were examined. The histology slides were reviewed, the number of cystic lesions was noted and also the clinical outcome. Out of the 270 patients nine presented with a cystic lesion and these were studied. Six cystic lesions were originally diagnosed as branchial cysts although the youngest age was 39 years. All patients underwent a simple excision. In six cases the tonsil was the primary site, in one the primary was in the base of tongue and in two the primary remained occult. One-third of the patients had died of their disease by the time this report was written and the maximum follow-up time for the remaining patients was 18 months. Therefore 16 per cent of branchial cysts in this series represented metastases from squamous cell carcinoma. At the Royal Liverpool University Hospital only 25 patients had branchial cysts excised between 1988 and 1993: out of these only four contained squamous carcinoma. In patients over 40 years of age panendoscopy and ipsilateral tonsillectomy is mandatory prior to cyst excision. PMID- 7861084 TI - Medical education: an audit of an overseas postgraduate training programme in ENT. AB - For overseas doctors, looking for higher training posts, the chance of being employed in the developed countries is becoming bleaker. This article considers the need for an increase in the number of local postgraduate training programmes in the Arab world in keeping with other developing countries. The model used for this study was an internal audit, of the postgraduate programme in ENT offered by King Faisal University in Dammam, Saudi Arabia. A dropout rate of more than 30 per cent among those who joined the programme reflected either the tougher standard of the course, or an inappropriate selection process. A major reason was the frustrating inability of the trainees to cope with the basic sciences course. This point was also addressed in the audit with a view to rationalizing the course to meet specific objectives. PMID- 7861085 TI - A new diagnostic approach to congenital stridor using a laryngeal mask airway and rigid endoscope. AB - Neonates with symptoms of stridor from birth, present a difficult diagnostic problem. We have demonstrated that by the use of a laryngeal mask airway in an anaesthetized baby breathing spontaneously, we are able to reach a diagnosis. This is accomplished by the introduction of a rigid fibre-optic endoscope through a Portex swivel connector and visualizing the glottis and larynx. PMID- 7861086 TI - First cleft branchial fistula in a child--a modified surgical technique. AB - Congenital first branchial cleft fistulae, their embryology, anomalies, varied relationships to the facial nerve and surgical techniques for their excision have been well described in the literature. We report a case of a type II first cleft fistula in a three-year-old child which required a modification of the standard surgical approach to achieve safe and complete excision with identification and preservation of the facial nerve. PMID- 7861087 TI - Epistaxis, von Willebrand's type bleeding diathesis and Wilms' tumour: a case report. AB - We report a case of persistent epistaxis in a seven-month-old child with Wilms' tumour who had an associated von Willebrand's type bleeding diathesis. Correction of the bleeding diathesis to control the epistaxis required treatment of the tumour with chemotherapy. PMID- 7861088 TI - Vile bodies: an endoscopic approach to nasal myiasis. AB - Nasal myiasis is the infestation of the nasal cavities by larvae (maggots) of Diptera flies. Several species of flies deposit their ova in the nose and the larvae feed on the host's tissues. We present a case of nasal myiasis by larvae of Oestrus ovis--Sheep Nasal Bot Fly. The larvae of Oestrus ovis are well known parasites in the nasal cavities and paranasal sinuses of sheep and goat. In Britain very rarely larvae may be deposited in the eye, nostrils or outer ear of man, usually husbandry workers. Reputedly, the larvae never survive beyond the first stage with acute catarrhal symptoms lasting only a few days. This is the first reported case in the UK of an urban-dwelling patient infected by mature, third instar larvae of O. ovis. His nasal infestation resolved after endoscopic removal of the live maggots. PMID- 7861089 TI - Laryngeal leishmaniasis. AB - A patient suffering from persistent hoarseness was eventually shown to have laryngeal leishmaniasis. The incubation period for the disease must have been at least 16 years, following infection in Southern Europe. Mucosal leishmaniasis is rare in the Eastern hemisphere, and laryngeal leishmaniasis has not previously been reported in the UK. Previous Mediterranean cases have run a similar chronic course and have caused diagnostic difficulty, in particular being mistaken for malignancy. Treatment with aminosidine was ineffective, but the patient responded to liposomal amphotericin. PMID- 7861090 TI - Laryngeal leishmaniasis as initial opportunistic disease in HIV infection. AB - A case of laryngeal leishmaniasis, with symptoms of hoarseness and odinophagia which had developed over the past year, is presented. Clinical features and histological findings are discussed. Visceral leishmaniasis is increasingly associated with HIV infection and some authors have suggested the possibility of including it as a diagnostic criterium for AIDS in HIV-positive patients. When any case of leishmaniasis presents atypical clinical features, localization or treatment response in endemic areas, HIV infection should be ruled out. PMID- 7861091 TI - Submental abscess: an unusual delayed complication of primary Blom-Singer valve insertion. AB - Voice restoration following laryngectomy can be achieved by the now well accepted technique of inserting a 'Blom-Singer' prosthesis through a tracheo-oesophageal fistula created either primarily or secondarily. Recognized complications of primary puncture and valve insertion include haemorrhage, oesophageal perforation, peristomal cellulitis and aspiration of saliva. We describe the previously unreported complication of a submental abscess developing probably as a result of air being forced from the fistula up between the trachea and the pharynx, this plane not having fully healed as a result of previous radiotherapy. The problem was compounded by the patient's over-zealous attempts to phonate. To prevent this problem arising in future we recommend leaving the fistula at least six weeks to mature before inserting the valve, when the patient has had previous radiotherapy, and encouraging relaxation when learning to phonate with this technique. PMID- 7861092 TI - Surgical management of a case of third branchial pouch fistula. AB - A case of left pyriform sinus fistula in a 20-year-old male is presented. The surgical management of this uncommon condition is discussed. Its embryological and clinical aspects are reviewed. PMID- 7861093 TI - Necrobacillosis--an unusual case of pharyngotonsillitis. AB - Necrobacillosis is a potentially life-threatening septicaemic illness occurring in the previously fit and healthy. The authors illustrate a case presenting as an atypical pharyngotonsillitis with renal complications, initially misdiagnosed as poststreptococcal glomerulonephritis. Necrobacillosis should be considered in cases of unusual pharyngotonsillitis. PMID- 7861094 TI - Metastasis in tongue from carcinoma of bronchus: a case report. AB - A case of carcinoma of the lung with a metastasis on the tongue is presented. The case is of interest because, although primary carcinomas of the tongue are fairly common accounting for 50 per cent of all oral carcinomas, metastatic tumour represents only one per cent of all malignant tumours of the oral cavity and of these only 0.2 per cent metastasize to the tongue. PMID- 7861095 TI - Fibromatosis of the parapharyngeal space. AB - Tumours of the parapharyngeal space are not common. The majority arise from the deep lobe of the parotid gland or neurovascular structures. We describe a case of fibromatosis, which has not previously been reported at this site. PMID- 7861096 TI - Aberrant thyroglossal cyst. AB - A case is presented of a laterally occurring thyroglossal cyst. In conventional teaching, thyroglossal duct remnants occupy the midline, or a position adjacent to the midline, and are found in a line marking the descent of the thyroid anlage and move upwards on protruding the tongue. Laterally presenting thyroglossal duct remnants are unusual. PMID- 7861097 TI - Expectorated tissue leading to diagnosis of renal adenocarcinoma. AB - Metastatic tumour to the tongue is extremely rare. We report a case of renal adenocarcinoma metastasis involving the right side of the base of the tongue with extension to the right vallecula in a 59-year-old man in which a piece of the metastatic lesion in the tongue was expectorated and was the first evidence of the primary tumour in the right kidney. Previously reported cases are reviewed. PMID- 7861098 TI - MR imaging features of an intracochlear acoustic schwannoma. AB - We present a very unusual case of an acoustic neuroma involving the left cochlea and internal auditory canal of a 24-year-old man. Clinical suspicion was aroused when the patient presented with a left total sensorineural hearing loss and continuing vertigo. The diagnosis was made pre-operatively with MRI after initial CT scanning was normal. The tumour was removed via a transotic approach. This case report demonstrates the MRI features of an intracochlear schwannoma and emphasizes the importance of MRI in patients with significant auditory and clinical abnormalities with normal CT scans of the relevant region. PMID- 7861099 TI - Temporal bone chondroblastoma: big and small. AB - Chondroblastoma represents approximately one per cent of all primary bone tumours. It is even rarer in the temporal bone and so far only 34 cases have been reported. We report here two cases with chondroblastoma of the temporal bone. The first case was discovered as a small lesion of the attic and root of zygoma. It was removed via mastoidectomy and reconstruction of the bony defect achieved normal external ear canal anatomy and hearing post-operatively. The second case presented as an advanced tumour involving the infratemporal fossa and parapharyngeal space. It was treated surgically via the infratemporal fossa approach. As clear surgical margins were not obtained, post-operative radiotherapy was also given to minimize the chance of recurrence. PMID- 7861100 TI - Primary health care computing analysis of Swedish maternal health records. AB - In our attempt to develop an "Essential Data Set" for a computer based information system to support Maternal & Child Health Care services an analysis of Swedish maternal care services was undertaken. The present study analyses the information system in the domain of maternal and child health care at the primary health center level with a view to identify areas where a computer-based medical record could effect improvements. The study showed that even in a well organized maternal care service as in Sweden lacunae exist in the information system. The paper forms, called MHV1, MHV2, MHV3 and FV1, though well designed, were incomplete in a large number of the cases. The MHV1 forms were completed in less than 45%, the MHV 2 form in 87.5% and the FV1 form in 70% of the cases. Certain elements of the data set were less likely to be completed than others. Another weak spot was the inaccessibility of the paper records during off-hours. These deficiencies could be eliminated by the use of a computerized medical record based on an essential data set. PMID- 7861101 TI - Status quo and future prospects of the total hospital information system of a Japanese medical college. AB - Six years have passed since the total hospital information system of Miyazaki Medical College, nicknamed PHOENIX, began its functions for the first time. It started with order entry systems, and has accomplished various systems, leaving one entry system unfinished; the injection order entry system which will be completed in the near future. It was revealed that the waiting period was most reduced at the hospital pharmacy. The waiting period for the visitors was also reduced. Usefulness of the PHOENIX system was greatly advanced by the function of a unique system of personal computer LAN, nicknamed PALM. This personal computer environments consisted of 200 or more Apple Macintosh computers. In this PALM environment, file servers, CD-ROM MEDLINE, clinical information databases, electronic mails (available in LAN and Internet) and sharing of printers are on service 24 hr a day. PMID- 7861102 TI - Microsoft Excel Program for creating attractive survival curves. AB - This paper describes the design of a Microsoft Excel Program which interactively creates attractive and outstanding survival curves. This program enables medical researchers to easily create quality presentation graphs of survival curves and obtain high quality slides and prints, which can be inserted in papers or used directly at medical meetings. Through the use of vertical bars, this program can display the exact points where censored cases occur on survival curves, making it possible to monitor censoring patterns between groups. Furthermore, this program can also create survival curves based on the proportional hazards model for specific patterns of covariate values, given estimated regression coefficients and baseline survival function. This program may be a most useful and effective tool in creating medical research papers containing survival analysis. PMID- 7861103 TI - A scheduling model for hospital residents. AB - When medical students finish their school they must go through a horrendous apprenticeship known as hospital residency to be able to practice medicine. During residency, they work at least 16-hr a day, 5-days a week, with 2 or 3 nights on-call. These can turn into 36-hr shifts. This means that many patients are being treated by exhausted novices, who are therefore much more likely to make mistakes. It was one such mistake, leading to the death of a New York woman, which led to serious attempts to reforming working hours of residents. In this paper, we developed a decision model which attempts to schedule residents based on the requirements of the residency program as well as the desires of residents as to days-off, weekends, on-call nights, etc. PMID- 7861104 TI - Voting and priorities in health care decision making, portrayed through a group decision support system, using analytic hierarchy process. AB - Within the health care industry many decision making approaches and tools are used. This paper explores a new tool, the Analytic Hierarchy Process (AHP), which permits both subjective and objective information to be considered in a decision. AHP has tremendous potential to solve both traditional and non-traditional health care problems. Its strength as a decision-making tool is its ability to combine both subjective and objective data. Application of AHP is discussed within the context of a Group Decision Support System (GDSS) model developed by Hatcher. The model is reviewed in limited detail, and readers are referred to the original article that defined and discussed the uniqueness and level of sophistication of GDSS applications in the health care industry. Health and medical delivery problems are discussed to highlight AHP requirements and the complexity of AHP applications. Health care applications are unique in that they lend themselves ideally to the use of computer data, image, voice, text, and multimedia concepts. PMID- 7861105 TI - How to structure clinical practice guidelines for continuous quality improvement? AB - The purpose of this study was to evaluate the relevance of available practice guidelines to clinical quality improvement programs. A sample of 19 guidelines was evaluated in four prominent primary care areas. Two research assistants independently coded the clinical conditions and recommended/not recommended procedures abstracted from the guidelines (Cohen's kappa .67 and .50, respectively). An average of 35.1 (+/- 25.8) medical conditions and 48.4 (+/- 41.5) clinical procedures were defined by the guidelines. Most conditions were defined by using ICD-9-CM, age/sex group, or therapy, but 29% of definitions included symptoms which are not coded routinely. CPT codes alone were unable to identify most procedures. AHCPR guidelines mentioned significantly more procedures (p < .001) and fewer symptoms (p < .001) per clinical condition than other guidelines. The difficulty of finding codes for conditions and procedures, the high rate of non-codable items, and the lack of recommended measures limit the applicability of published clinical practice guidelines to continuous quality improvement programs. PMID- 7861106 TI - Perhaps there is a Santa Claus. PMID- 7861107 TI - Complications of plombage in a Cuban exile. AB - Collapse of the affected lung, or plombage, was a common operative treatment for tuberculosis in the United States in the 1930s and 40s. Due to the lack of antitubercular drugs, this practice continued in Cuba into the 1950s. After 41 years the plombage material in an exile patient was found to be infected. This resulted in the bronchopleural fistula which required a pectoralis muscle flap to close. Physicians should be aware that many Cuban exiles have been treated for tuberculosis via plombage and are at risk for similar complications. PMID- 7861108 TI - Tobacco. The leading cause of death. AB - More than 400,000 persons die in the United States each year from tobacco-related causes; over 28,000 are Floridians. The Centers for Disease Control and Prevention, State Health Office, and Florida Department of Education have developed sophisticated systems for measuring prevalence of tobacco use in the general population and selected subgroups and for estimating smoking-attributable mortality, morbidity and economic cost. They are: Behavioral Risk Factor Surveillance System, Smoking-Attributable Mortality, Morbidity and Economic Cost, Youth Risk Behavior Survey, and Pregnancy Risk Assessment Monitoring System. Each system is described, including selected national and state data which help identify patients at risk and provide education and smoking cessation services. PMID- 7861109 TI - Attempted suicide or hitting the nail on the head. Case report. AB - A case is reported of attempted suicide by hammering nails through the skull into the brain. This unique attempt at self-destruction was unsuccessful and the treatment, initially by an untrained first-aider and then by a neurosurgeon, was surprisingly simple. There were no long-term sequelae. PMID- 7861110 TI - Physician attitudes toward nurse-midwives. Results of 1993 survey. AB - Physicians and certified nurse-midwives have worked together in hospitals, private practices, clinics and birth centers throughout Florida for over 20 years. A questionnaire was sent to all maternal health-care providers to develop an understanding of the perceived attitudes, benefits, or liabilities of the professional relationships between them. An analysis is provided of the 374 physician responses. PMID- 7861111 TI - Repetitive motion disorders of the upper extremity. Strategies for computer keyboard operators. PMID- 7861112 TI - Economic credentialing. The buck stops here. PMID- 7861113 TI - Activity-dependent regulation of dendritic spine density on cortical pyramidal neurons in organotypic slice cultures. AB - In order to examine the effects of activity on spine production and/or maintenance in the cerebral cortex, we have compared the number of dendritic spines on pyramidal neurons in slices of P0 mouse somatosensory cortex maintained in organotypic slice cultures under conditions that altered basal levels of spontaneous electrical activity. Cultures chronically exposed to 100 microM picrotoxin (PTX) for 14 days exhibited significantly elevated levels of electrical activity when compared to neurons in control cultures. Pyramidal neurons raised in the presence of PTX showed significantly higher densities of dendritic spines on primary apical, secondary apical, and secondary basal dendrites when compared to control cultures. The PTX-induced increase in spine density was dose dependent and appeared to saturate at 100 microM. Cultures exhibiting little or no spontaneous activity, as a result of growth in a combination of PTX and tetrodotoxin (TTX), showed significantly fewer dendritic spines compared to cultures maintained in PTX alone. These results demonstrate that the density of spines on layers V and VI pyramidal neurons can be modulated by growth conditions that alter the levels of spontaneous electrical activity. PMID- 7861114 TI - Expression of the ligand-binding nicotinic acetylcholine receptor subunit D alpha 2 in the Drosophila central nervous system. AB - The D alpha 2 gene encodes a ligand-binding subunit of nicotinic acetylcholine receptors (nAChRs) from Drosophila melanogaster. We have studied the distribution of D alpha 2 transcripts and protein by in situ hybridization and immunohistochemistry, respectively, as well as the regulation of D alpha 2 gene expression in vivo using D alpha 2 promoter fragments fused to the Escherichia coli lacZ gene. Transcripts and protein from the D alpha 2 gene were detected exclusively in the central nervous system. Both in late embryos and adults D alpha 2-like immunoreactivity is widely but not uniformly distributed in the synaptic neuropil, suggesting that the D alpha 2 protein is a subunit of a synaptic nicotinic receptor. Its distribution resembles that of ALS and ARD proteins, two other nAChR subunits of the fly. Five different D alpha 2-lacZ fusion gene constructs were introduced into the Drosophila genome by P-element mediated gene transfer to identity functional elements of the D alpha 2 promoter. All constructs produce a basic lacZ expression pattern that is compatible with the distribution of D alpha 2 transcripts and protein. A 880 bp upstream fragment harbors the cis elements for the expression of a weak but specific basic D alpha 2 pattern. The next 350 bp further upstream significantly enhance beta galactosidase expression without influencing the pattern of expression. Between 1.7 and 7.3 kb upstream of the transcription start site one or more elements that are required for D alpha 2 expression in optic lobe tangential cells are located. PMID- 7861115 TI - The growth of PC12 neurites is biased towards the anode of an applied electrical field. AB - We have exposed cultures of PC12 cells to uniform DC electric fields following the addition of NGF. The success of these experiments relied upon the design of new chambers enabling fields to be applied to mammalian cell cultures. After 48 h of field application, the distribution of neurite outgrowths was biased towards the anode. More neurites faced the anode than would be expected if growth was uniform. The magnitude of this bias was strongly correlated with field strength, with a threshold value of about 1 mV/mm. At field strengths above 30 mV/mm, the neurites growing towards the cathode were shorter than those growing towards the anode or perpendicular to the field. This response was not correlated with field strength. This report confirms that mammalian neurons respond to electrical fields and supports the notion that neurites are influenced by endogenous electrical fields during development. As far as we are aware, this is the only report that documents a response towards the anode. PMID- 7861116 TI - Expression of trk and neurotrophin mRNA in dorsal root and sympathetic ganglia of the quail during development. AB - The nerve growth factor (NGF) family of neurotrophins exerts effects by binding to products of the trk family of proto-oncogenes. We examined the expression of both trk and neurotrophin mRNA during the entire range of development of quail dorsal root ganglia (DRG) and sympathetic ganglia (SG) using in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR). TrkC mRNA was present in neurons or their precursors from the time of formation of DRG (stage 18, embryonic day 2.5 [E2.5]) and throughout development. The number of labeled cells changed, however, from a majority to a minority at later developmental stages. Expression of trkA mRNA was not detected in DRG until stage 30 (E6) by in situ hybridization, although results with RT-PCR were positive at stage 23 (E3.5). Labeling was always detected on a majority of neurons or their precursors. SG exhibited low levels of trkC mRNA during the later stages of development, whereas trkA mRNA was present from stage 34 onward in most neurons. We have also shown that NGF, neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF) mRNA were present at all stages examined (stages 23 through 45 for DRG, stages 35-36 and 45 for SG). In DRG, NGF mRNA expression was limited to support cells, whereas NT-3 and BDNF mRNA were detected in both neurons and support cells. These results suggest that neurotrophins could serve a local function in developing ganglia, which can be correlated with the presence of their respective receptors. PMID- 7861117 TI - GABAA receptor subunit polypeptides increase in parallel but exhibit distinct distributions in the developing rat cerebellum. AB - The GABAA receptor, a multisubunit ligand-gated ion channel, plays a central role in cell-cell communication in the developing and adult nervous system. Although the developmental expression of mRNAs encoding many subunit isoforms has been extensively characterized throughout the central nervous system, little is known concerning the relationship between subunit mRNA and polypeptide expression. To address this issue, we examined the developmental expression of the alpha 1, beta 2/3, and gamma 2 subunit polypeptides, subunits that are thought to coassemble in many brain regions. Western blot analysis using subunit-specific antibodies revealed that the levels of these polypeptides in both the cerebral cortex and cerebellum increased severalfold during the second postnatal week. Whereas polypeptide expression in the cerebellum paralleled that of the corresponding subunit mRNAs, increases in beta 2/3 and gamma 2 polypeptide expression in the cerebral cortex occurred in the absence of detectable changes in the mRNA levels. To determine whether the increases in subunit polypeptide expression in the cerebellum were accompanied by changes in distribution, immunohistochemistry was performed. These studies demonstrated that the subunits exhibited different but partially overlapping distributions that remained constant throughout postnatal development. Our findings suggest that although GABAA receptor subunit polypeptide expression may be regulated primarily at the level of the mRNA, additional regulatory mechanisms may play a role. Furthermore, the observation that subunit distribution remains constant in the cell bodies of cerebellar Purkinje neurons, which express the alpha 1, beta 2, beta 3, and gamma 2 subunit mRNAs exclusively, suggests that GABAA receptor subunit composition in this cell population does not change during postnatal maturation. PMID- 7861118 TI - Pharmacological characterization of a serotonin receptor involved in an early embryonic behavior of Helisoma trivolvis. AB - In contrast to the abundance of information on the many physiological and developmental actions of serotonin in molluscan nervous systems, comparatively little is known about the serotonin receptors involved in these responses. Embryos of the pulmonate gastropod, Helisoma trivolvis, display a cilia-driven rotational behavior that is regulated by endogenous serotonin. In the present study, two functional assays were used to determine some of the pharmacological properties of the receptors that mediate the cilio-excitatory action of serotonin. Time-lapse video microscopy was used to measure whole embryo rotation rate and cilia beat frequency in isolated cells. In dose-response experiments, serotonin was approximately 10 times more potent in stimulating cilia beat frequency over embryo rotation. In rotation experiments, 5-carboxyamidotryptamine and methysergide had effective agonist activity in dose ranges similar to that of serotonin (1 to 100 microM). In contrast, 8-hydroxydipropylaminotetralin HBr (8 OH-DPAT) displayed agonist activity of lower potency and effectiveness. Several compounds displayed antagonist activity in the 1 to 100 microM dose range, including mianserin, spiperone, ritanserin, 1-(1-naphthyl)piperazine, and propranolol. alpha-Methylserotonin had mixed agonist-antagonist activity, and metoclopramide, MDL-72222, and ketanserin were inactive. Experiments on isolated cells suggested that the extremely effective antagonism displayed by mianserin in the embryo rotation assay was due to its specific activity at ciliary serotonin receptors. These results implicate the presence of a novel serotonin receptor on embryonic ciliated cells that is pharmacologically distinct from those previously characterized in vertebrate or invertebrate systems. PMID- 7861119 TI - Outgrowth morphology and intracellular calcium of crustacean neurons displaying distinct morphologies in primary culture. AB - Peptide-secreting neurons from crustacean X-organ regenerating in defined culture possess different ionic current profiles correlated with two distinct morphological types, veiling and branching; voltage-dependent Ca2+ current is prominent in neurons consistently extending large veils, but is small in neurons that repetitively branch. Intracellular free calcium levels ([Ca2+]i) have been implicated in the regulation of neurite outgrowth underlying the establishment of distinct morphologies. Here, basal [Ca2+]i was measured by fura-2 fluorescence ratio imaging from these morphologically distinct neurons and compared. Both morphological types can extend out processes over a [Ca2+]i range (approximately 50 to 300 nM) that is much greater than that reported for neurons of other phyla. Application of high K+ saline led to increases in [Ca2+]i in soma, neurite, and lamellipodium of veiling neurons. Increases were greater for veiling than branching neurons. These observations were consistent with the previous voltage clamp data for calcium currents. Media altered to perturb [Ca2+]i were used to assess the role of [Ca2+]i in veiling or branching outgrowth programs. Outgrowth of veiling cells was arrested by addition of 100 microM Cd2+, a calcium channel blocker. Outgrowth resumed following brief exposures to Cd2+. Branching neurons were unaffected by Cd2+. Cd2+ at lower levels (10 microM) had no effect on outgrowth of either neuronal type, whereas at higher levels (1 mM), outgrowth of both types was arrested. Reduction of extracellular sodium to 0.001 of normal concentration stopped veiling outgrowth, but branching outgrowth continued, although it was less robust. Addition of tetrodotoxin (1 microM) did not alter outgrowth of either neuronal type relative to controls. Thus, peptidergic neurons of differing intrinsic morphologies maintain similar basal [Ca2+]i levels under identical culture conditions, yet show differing sensitivities to manipulations influencing [Ca2+]i with respect to regenerative outgrowth, but not its form. PMID- 7861120 TI - GAP-43 immunoreactivity and axon regeneration in retinal ganglion cells of the rat. AB - Retinal ganglion cells (RGCs) in rats were retrogradely labeled with the fluorescent tracer Fluorogold (FG) and subjected to GAP-43 and c-JUN immunocytochemistry to identify those RGCs that are capable of regenerating an axon. After optic nerve section (ONS) and simultaneous application of FG to the nerve stump (group 1 experiments), GAP-43 immunoreactive RGCs (between 2 and 21 days after ONS) always represented a subfraction of both FG-labeled (i.e., surviving) RGCs and RGCs exhibiting c-JUN. GAP-43 immunoreactive RGCs represented 22% of RGCs normally present in rat retinae and 25% of surviving RGCs at 5 days after ONS but were reduced to 2% and 1%, which is 6% and 5% of survivors at 14 and 21 days, respectively. In animals that received a peripheral nerve (PN) graft after ONS (group 2 experiments), RGCs with regenerating axons were identified by FG application to the graft at 14 and 21 days. When examined at 21 and 28 days, all FG-labeled RGCs exhibited GAP-43 immunoreactivity, and FG/GAP-43-labeled RGCs were 3% and 2% of those present in normal rat retinae. In relation to surviving RGCs GAP-43 immunoreactive RGCs represented 10% at both time points. FG-/GAP-43 labeled RGCs also exhibited c-JUN, but c-JUN immunoreactive RGCs were at both time points at least twice as numerous as FG-/GAP-43-labeled RGCs. These data suggest that regenerating axons in PN grafts derive specifically from GAP-43 reexpressing RGCs. Appearance of GAP-43 immunoreactivity may therefore identify those RGCs that are capable of axonal regeneration or sprouting. PMID- 7861121 TI - Neurons in culture maintain acetylcholine receptor levels with far fewer transcripts than in vivo. AB - Of the 10 neuronal nicotinic acetylcholine receptor (AChR) genes identified in chick, five are expressed by ciliary ganglion neurons in vivo (alpha 3, alpha 5, alpha 7, beta 2, and beta 4), and the mRNA levels produced increase during development approximately in parallel with the two major classes of AChRs present. Here we report that when chick ciliary ganglion neurons from 8-day embryos are transferred to dissociated cell culture, they express the same five genes but at much lower levels. The alpha 3 and alpha 7 transcripts, chosen for detailed analysis because they encode subunits segregated between the two AChR species, decrease rapidly in abundance on transfer to culture and, after 1 week, are at levels less than a 20th of those found in vivo for neurons of the same age. Co-culturing the neurons with skeletal myotubes did not increase the levels of AChR transcripts in the neurons. Despite low amounts of mRNA from all five genes, neither class of AChRs was much reduced in culture compared to in vivo. The numbers of AChRs on the cell surface actually increased with time in culture. Several culture conditions known to down-regulate the receptors in culture did not reduce the abundance of the alpha 3 and alpha 7 mRNAs. The results suggest that post-transcriptional controls can play an important role in determining AChR abundance on the neurons. PMID- 7861122 TI - Involvement of protein kinase C in the axonal growth-promoting effect on spinal cord neurons by target-derived astrocytes. AB - Astroglial cells participate in a variety of developmental events during neuronal morphogenesis. We have shown that axonal, but not dendritic, outgrowth of spinal cord neurons can be promoted by a diffusible factor or factors secreted from target region-derived cerebellar astroglia in vitro in comparison with spinal astroglia. In the present study, we examined the involvement of protein kinase C (PKC) in the axon-promoting effect by astroglia. The inhibition of PKC by sphingosine or by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) at high concentration greatly reduced the mean axonal length of spinal neurons cultured in medium conditioned by cerebellar astroglia (SCn-CBg), while activation of PKC by TPA at low concentration, or by retinoic acid, was not additive to the glial effect. The activation of PKC by TPA or retinoic acid promoted axon growth of spinal neurons cultured in medium conditioned by spinal astroglia (SCn-SCg), which otherwise would not be as supportive for axon growth as cerebellar astroglia. Western blotting and PKC activity assays showed that there was a trend for increased PKC activity and protein levels (in particular, PKC beta) in SCn-CBg cultures, which correlated with enhanced axon growth. Inhibition of PKC by sphingosine appeared to decrease protein levels, especially PKC beta, which correlated with suppressed axon outgrowth. In SCn-SCg cultures, phorbol ester activation of PKC increased both activity and protein levels of both PKC alpha and PKC beta. This activation correlated with stimulated axonal outgrowth. These results suggest that the glial signaling that regulates specific axonal outgrowth by target astroglia is mediated in part by the PKC second messenger system. PMID- 7861123 TI - Target specificity and size of avian sensory neurons supported in vitro by nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3. AB - To obtain insight into which subpopulations of sensory neurons in dorsal root ganglia are supported by different neurotrophins, we retrogradely labeled cutaneous and muscle afferents in embryonic day 9 chick embryos and followed their survival in neuron-enriched cultures supplemented with either nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), or neurotrophin-3 (NT-3). We found that NGF is a wide survival factor for subpopulations of both cutaneous and muscle afferents, whereas the survival effects of BDNF and NT-3 are restricted primarily to muscle afferents. We also measured soma size in each neurotrophic factor. These new data show that BDNF- and NT-3-dependent cells appear to be a mixture of two populations of neurons: one small diameter and the other large diameter. In contrast, based on size alone, NGF-dependent cells appear to be a single population of only small-diameter neurons. Thus, BDNF and NT-3 may have some new, previously unreported effects on small-diameter afferent neurons. PMID- 7861124 TI - Androgen directs sexual differentiation of laryngeal innervation in developing Xenopus laevis. AB - In adult Xenopus laevis, innervation of the vocal organ is more robust in males than in females. This sex difference originates during tadpole development; at stage 56, when the gonads first differentiate, the number of axons entering the larynx is the same in the sexes, but by stage 62, innervation is greater in males. To determine if androgen secretion establishes sex differences in axon number, we treated tadpoles with antiandrogen or androgen beginning at stage 48 or 54 and counted laryngeal nerve axons at stage 62 using electron microscopy. When male tadpoles were treated with the antiandrogen hydroxyflutamide, axon numbers were reduced to female-typical values; axon numbers in females were unaffected by antiandrogen treatment. When female tadpoles were treated with the androgen DHT (dihydrotestosterone), axon numbers were increased to male-like values. These findings suggest that endogenous androgen secretion during late tadpole stages in males is required for the sexual differentiation of laryngeal innervation observed from stage 62 on. Because androgen treatment and laryngeal innervation affect myogenesis in postmetamorphic frogs, numbers of laryngeal dilator muscle fibers were determined for hormonally manipulated tadpoles. At stage 62, vehicle-treated males had more laryngeal axons than females; laryngeal muscle fiber numbers did not, however, differ in the sexes. Both male and female tadpoles, treated from stage 54 with DHT, had more muscle fibers at stage 62 than vehicle-treated controls. Thus, while endogenous androgen secretion during late tadpole stages is subthreshold for the establishment of masculinized muscle fiber numbers, laryngeal myogenesis is androgen sensitive at this time and can be increased by suprathreshold provision of exogenous DHT. A subgroup of tadpoles, DHT treated from stage 54 to 62, was allowed to survive, untreated, until postmetamorphic stage 2 (PM2: 5 months after metamorphosis is complete). Androgen treatment between tadpole stages 54 and 62 does not prevent the ontogenetic decrease in axon numbers characteristic of laryngeal development. In addition, the elevation in stage 62 axon numbers produced by DHT-treatment at late tadpole stages was not associated with elevated numbers of laryngeal muscle fibers at PM2. Juvenile males normally maintain elevated axon numbers (relative to final adult values) through PM2 and the presence of these additional axons may result from--rather than contribute directly to--laryngeal muscle fiber addition. PMID- 7861125 TI - Long-term survival followed by degradation of neurofilament proteins in severed mauthner axons of goldfish. AB - The morphology and protein composition of intact and severed Mauthner axons (M axons) from goldfish were examined on electron micrographs, sodium dodecyl sulfate gels, and immunoblots. Neurofilaments were the most common cytoskeletal element on electron micrographs, and neurofilament proteins (NFPs) were the most intensely silver-stained bands in M-axoplasm microdissected from control M-axons. NFPs at about 235, 145, 123, 105, 80, and 60 kD in M-axoplasm were identified with four monoclonal and three polyclonal antibodies. Similar immunoblots of samples of the M-axon myelin sheath (M-sheath) showed no reactivity to antibodies against NFPs. For up to 62 days following spinal cord severance in goldfish maintained at 15 degrees C, the ultrastructure, protein banding pattern, and anti NFP immunoreactivity of several distal segments of M-axons did not change compared with control M-axons. At 62 to 81 days after severance, novel bands appeared in many silver-stained gels and anti-NFP immunoblots of distal M-axons. NFP bands completely disappeared from distal M-axon segments of some M-axons as early as 72 days after severance. However, NFP bands persisted in some distal segments for up to 81 days after severance. The degradation of NFPs occurred equally along the entire length of a distal M-axon segment, that is, there was no indication of a proximal-to-distal or distal-to-proximal sequence of NFP degradation in distal segments of severed M-axons. These biochemical data were consistent with morphological data that showed little change in the diameter or ultrastructure of severed M-axons held at 15 degrees C for about 2 months followed by a rapid collapse of the entire distal segment at 72 to 85 days postseverance. PMID- 7861126 TI - Antioxidant effect of copper(II) on photosensitized lipid peroxidation. AB - Unilamellar liposomes (LH) of phosphatidylcholine (PC), dispersed in phosphate buffer at pH 7 (PB), underwent lipid peroxidation and lysis with release of entrapped glucose-6-phosphate when irradiated with UVA light in the presence of 2 (3-benzoylphenyl)propionic acid (ketoprofen, KPF) or 2-(6-methoxy-2 naphthyl)propionic acid (naproxen, NAP), which were used as photosensitizers. Lipid photoperoxidation and consequent lysis were reduced when copper(II), up to 5 microM, was present in the irradiated samples. Suitable experiments were performed to evidence the species responsible for the lipid peroxidation, the copper effect on the drug photodegradation, and the mechanism of the copper antioxidant activity. The overall results suggest that the photoperoxidation was probably initiated by organic radicals obtained from the irradiation of KPF and NAP and the inhibition by copper could be attributed to its interaction with the peroxyl radicals of the drug and/or the liposomes, breaking the propagation of the radical chain. PMID- 7861127 TI - Mechanisms of formation and decomposition of hypervalent chromium metabolites in the glutathione-chromium (VI) reaction. AB - A long-lived chromium(IV) intermediate is generated during the reaction between Cr(VI) and glutathione in glycine below pH 3. The intermediate reacts with the tripeptide to produce Cr(III) and oxidized glutathione. A dynamic magnetic susceptibility measurement based on a nuclear magnetic resonance method yielded a 2.8 microB magnetic movement for the chromium(IV) species. The intermediate is formed by parallel third-order and second-order processes. The third-order process (k = 5.9 x 10(2) M-2 s-1) involves first-order participation by each of the oxidant, reductant, and hydrogen ions. A hydrogen ion independent pathway leads to a sluggish second-order process (k = 0.11 M-1 s-1) that is first order with respect to reduced glutathione [GSH] and [Cr(VI)]. Chromium(IV) species is reduced to Cr(III) by a second-order process (k = 0.13 M-1 s-1) that is first order in each of [Cr(IV)] and [GSH] and does not depend on [H+]. At pH 3.4, a chromium(V) species was detected as a minor intermediate as well. In the pH range 6.5-7.5, three dominant chromium(V) intermediates were detected. The existence of Cr(IV) in low pH offers an opportunity to examine the mechanism of DNA damage by this rare oxidation state. PMID- 7861128 TI - HPLC investigation on Ni(II)-mediated DNA damage in the presence of t-butyl hydroperoxide and glutathione. AB - By use of HPLC with UV and electrochemical detection, the present study demonstrates that reaction of Ni2+ with t-butyl hydroperoxide in the presence of glutathioine (GSH) generates 8-hydroxy-2'-deoxyguanosine (8-OH-dG) from 2' deoxyguanosine (dG) and from dG residues in calf thymus DNA at physiological pH. No significant amount of 8-OH-dG was generated in the absence of GSH, indicating an important role of GSH in enhancing the reactivity of Ni2+ toward lipid hydroperoxide to oxidize dG or dG residues in DNA. The rate of dG conversion to 8 OH-dG depends on the concentration of the reagents. During a two hour incubation of 0.75 mM dG, 10 mM t-butyl hydroperoxide, 1 mM Ni2+, and 2 mM GSH at room temperature under ambient air, dG was converted to 8-OH-dG with a yield of about 0.2%. For dG residues in DNA, 24 hour incubation at 37 degrees C yielded 0.1% 8 OH-dG. The 8-OH-dG generation from both dG and dG residues in DNA was inhibited by superoxide dismutase, catalase, and ethanol (hydroxyl radical scavenger), implying the involvement of oxygen free radicals in the 8-OH-dG generation process. The metal ion chelators, deferoxamine and EDTA, efficiently inhibited the 8-OH-dG formation. Similar results were obtained for the conversion of dG residues in calf thymus DNA to 8-OH-dG. Electrophoretic assays of DNA strand breaks showed that Ni2+ caused DNA double-strand breaks in the presence of t butyl hydroperoxide and GSH. Because GSH is ubiquitously present in cellular systems at relatively high concentration, and the exposure of cells to Ni2+ results in the generation of lipid hydroperoxides, the 8-OH-dG generation and DNA double-strand breaks caused by the reaction of Ni2+ with lipid hydroperoxides in the presence of GSH may be an important mechanism in Ni(2+)-induced carcinogenesis. The inhibitory effect of chelators suggests a possible prevention strategy against Ni(2+)-induced toxicity and carcinogenesis. PMID- 7861129 TI - Cultured astrocytes release a factor that decreases endothelin-1 secretion by brain microvessel endothelial cells. AB - Endothelin-1 (ET-1), originally characterized as a potent vasoconstrictor peptide secreted by vascular endothelial cells, has now been described to possess a wide range of biological activities within the cardiovascular system and in other organs. Brain microvessel endothelial cells, which, together with perivascular astrocytes, constitute the blood-brain barrier, have been shown to secrete ET-1, whereas specific ET-1 receptors are expressed on astrocytes. It is reported here that conditioned medium from primary cultures of mouse embryo astrocytes could significantly, and reversibly, attenuate the accumulation of both ET-1 and its precursor big ET-1 in the supernatant of rat brain microvessel endothelial cells by up to 59 and 76%, respectively, as assessed by immunometric assay. This inhibitor of ET-1 production was purified by gel-exclusion and ion-exchange chromatography as a 280-Da iron-containing molecule, able to release nitrites upon degradation. These results suggest that astrocytes, via release of an iron nitrogen oxide complex, may be involved in a regulatory loop of ET-1 production at the level of the blood-brain barrier. PMID- 7861130 TI - Cellular expression, developmental regulation, and phylogenic conservation of PEA 15, the astrocytic major phosphoprotein and protein kinase C substrate. AB - PEA-15 has recently been identified as a major phosphoprotein in astrocytes and an endogenous substrate for protein kinase C. This 15-kDa protein exists under three molecular forms, an unphosphorylated form, N, and two phosphorylated forms, Pa and Pb. Antisera were raised against synthetic peptides corresponding to the internal sequences of the mouse protein containing the two specific phosphorylation sites and affinity-purified antibodies were used for immunoblotting. PEA-15 was found mainly in the cytosol, but its protein kinase C phosphorylated form, Pb, was also detectable in association with the membrane and remained with the fraction that contains stabilized microtubules. Abundant in astrocytes, particularly in the hippocampus, PEA-15 was also detected in all cultured brain cell types examined, indicating a more ubiquitous distribution of the protein, further demonstrated by its detection in the eye and in the lung. Parallel to the increase in expression levels, phosphorylation of PEA-15 also increased during development. This paralleled results obtained in primary cultures, whereas PEA-15 levels increase with cell maturation. Finally, physiological importance of PEA-15 phosphorylation was illustrated by immunoreactivity observed in brain homogenates of different mammals, birds, amphibians, and fish. PMID- 7861131 TI - Localization of glycine neurotransmitter transporter (GLYT2) reveals correlation with the distribution of glycine receptor. AB - We studied by immunocytochemical localization, the glycine neurotransmitter transporter (GLYT2) in mouse brain, using polyclonal antibodies raised against recombinant N-terminus and loop fusion proteins. Western analysis and immunocytochemistry of mouse brain frozen sections revealed caudal-rostral gradient of GLYT2 distribution with massive accumulation in the spinal cord, brainstem, and less in the cerebellum. Immunoreactivity was detected in processes with varicosities but not cell bodies. A correlation was observed between the pattern we obtained and previously reported strychnine binding studies. The results indicate that GLYT2 is involved in the termination of glycine neurotransmission accompanying the glycine receptor at the classic inhibitory system in the hindbrain. PMID- 7861132 TI - Heterogeneous expression of transketolase in rat brain. AB - Transketolase (TK; EC 2.2.1.1) is a key pentose phosphate shunt enzyme that plays an important role in the production of reducing equivalents and pentose sugars. TK activity declines in the brains of patients with Alzheimer's disease or Wernicke-Korsakoff syndrome, as well as in thiamine-deficient rats. Understanding the role of TK in the pathophysiology of these neurodegenerative conditions requires knowledge of its regional, cellular, and subcellular distribution within the brain. The current study employed in situ hybridization and immunocytochemistry to examine the distribution of TK mRNA and its encoded protein in adult rat brain. TK mRNA and protein were widely distributed throughout the brain. However, they were enriched in selective perikarya in the piriform cortex, nucleus of the diagonal band, red nucleus, dorsal raphe, pontine nucleus, locus coeruleus, trapezoid, inferior olive, and several cranial nerve nuclei. Lower expression of TK mRNA and protein occurred in layer V of cortex, olfactory tubercle, ventral pallidum, medial septal nucleus, hippocampus, thalamic and hypothalamic nuclei, mammillary body, central gray, and the substantia nigra. TK immunoreactivity also occurred in the nuclei of ubiquitously distributed glial cells, as well as ependymal cells. The heterogeneous distribution of TK may reflect a variety of metabolic activities among different brain regions but does not provide a simple molecular explanation for selective cell death in either thiamine deficiency or other conditions where TK is reduced. PMID- 7861133 TI - Tau and microtubule-associated protein 2c transfection and neurite outgrowth in ND 7/23 cells. AB - Neuronal hybrid ND 7/23 cells, which display sensorylike properties, develop neurites when cultured in the presence of either dibutyryl cyclic AMP plus nerve growth factor (DBcAMP + NGF) or retinoic acid or a phorbol ester derivative, although they express only trace amounts of the microtubule-associated tau proteins and low levels of microtubule-associated protein 2c (MAP2c). Nondifferentiated ND cells transfected with tau cDNAs did not develop neurites, whereas very short cell processes were formed in MAP2c-transfected cells. tau and MAP2 antibodies labeled microtubule bundles displayed in a ring array underneath the surface of the transfected cells and short microtubules starting from the cell center. After differentiation in the presence of DBcAMP + NGF, the same bundle organization was observed in the transfected cells. In addition, tau and MAP2 antibodies stained a short section of the formed neurites. These data demonstrate that the expression of tau protein is not sufficient to induce neurite extension and that other proteins induced by morphogens are more important to initiate morphological differentiation of this cell line. PMID- 7861134 TI - Inhibition of drug-induced apoptosis by survival factors in PC12 cells. AB - Pheochromocytoma (PC12) cells have been shown to undergo apoptosis (programmed cell death) when deprived of serum and to be rescued by nerve growth factor, fibroblast growth factor, dibutyryl cyclic AMP, aurintricarboxylic acid, or exogenous expression of bcl-2. We show here that the cytotoxic drugs cycloheximide, actinomycin D, colchicine, and EGTA also induce apoptosis in PC12 cells. These findings prompted us to investigate whether apoptosis induced by these drugs involves similar pathways in each case, and whether the factors preventing the apoptotic death of serum-deprived PC12 cells can also protect the cells from apoptosis induced by the cytotoxic drugs. Nerve growth factor, dibutyryl cyclic AMP, and expression of bcl-2 inhibited apoptosis induced by all four cytotoxic drugs. Fibroblast growth factor inhibited apoptosis induced by EGTA or colchicine. Aurintricarboxylic acid inhibited apoptosis induced by EGTA. These results suggest that apoptosis induced by treatments with the various drugs is mediated by different initiating pathways, all of which converge into a final, common pathway. Nerve growth factor, dibutyryl cyclic AMP, and bcl-2 appear to affect the final common pathway, whereas fibroblast growth factor and aurincarboxylic acid appear to be more specific and affect only some of the pathways. PMID- 7861135 TI - Accumulation of 3H-phosphoinositides mediated by muscarinic receptors in the developing chick retina: inhibition of carbachol-induced response by glutamate receptors. AB - In the present work we show the development of carbachol-induced accumulation of 3H-inositol phosphates (3H-InsPs) in the chick embryonic retina and its regulation by glutamate receptors. Although basal levels of 3H-InsPs increased during development, the retinal response to carbachol was high in the early developing stages and decreased after synaptogenesis in the retina. Eserine also stimulated the turnover of phosphoinositides in the embryonic but not in the mature retina. The effect of eserine could be blocked by atropine, suggesting that acetylcholine could be released from developing retina cells and further stimulate the turnover of InsPs in the embryonic tissue. Our data also show that muscarinic stimulation of turnover of 3H-InsPs could be blocked by stimulation of glutamatergic ionotropic receptors. Moreover, the effect of glutamate agonists did not seem to be mediated by the release of other neurotransmitters such as GABA, glycine, adenosine, or dopamine from the tissue because these neurotransmitters did not interfere with the retinal response to carbachol. These results suggest that muscarinic activation of phosphoinositide turnover occurs mainly in the embryonic retina and that activation of glutamate receptors can inhibit directly the muscarinic stimulation of hydrolysis of 3H-InsPs in this tissue. PMID- 7861136 TI - Signal flows from two phospholipase C-linked receptors are independent in PC12 cells. AB - Bradykinin (BK) receptor and P2-purinergic receptor are known to be coupled to phospholipase C (PLC) in PC12 cells. To study the interaction between these two PLC-linked receptors, the presence of both receptors on individual cells was demonstrated by sequential Ca2+ spikes caused by BK and ATP in a single fura-2 loaded cell. BK- and ATP-induced catecholamine (CA) secretions were desensitized within 5 min. However, in the sequential experiment, the BK-induced homologous desensitization of CA secretion did not block the ATP-induced secretion, and vice versa. Each agonist-induced an increase in inositol 1,4,5-trisphosphate (IP3) production and intracellular free Ca2+ concentration also led to homologous desensitization. However, there was no heterologous desensitization between the two agonists. When the cells were treated with both BK and ATP simultaneously, the amounts of CA secretion, IP3 production, internal Ca2+ mobilization, and Ca2+ influx were all additive. We also found that both IP3-induced Ca2+ release from intracellular Ca2+ stores and Ca2+ influx from extracellular space were able to release [3H]norepinephrine, and the secretion induced by both agonists was exactly additive in the absence or presence of extracellular Ca2+. The data suggest that the CA secretions caused by BK or ATP may have separate secretory pathways even though they activate identical second messenger pathways. PMID- 7861137 TI - Natriuretic peptides inhibit nicotine-induced whole-cell currents and catecholamine secretion in bovine chromaffin cells: evidence for the involvement of the atrial natriuretic factor R2 receptors. AB - There is increasing evidence that members of the natriuretic peptide family display sympathoinhibitory activity, but it remains uncertain which receptor pathway is implicated. We performed cyclic GMP production studies with chromaffin cells treated with either atrial natriuretic factor (ANF) or C-type natriuretic peptide (CNP) and found that these cells specifically express the ANF-R1C but not the ANF-R1A receptor subtype. Evidence for the existence of ANF-R2 receptors was obtained from patch-clamp experiments where C-ANF, an ANF-R2-specific agonist, inhibited nicotinic currents in single isolated chromaffin cells. Involvement of ANF-R2 receptors in the modulation of nicotinic currents was further supported by the significant loss of this inhibitory activity after the cleavage of the disulfide-bridged structure of C-ANF. This linearized form of C-ANF also displayed a lower binding affinity for ANF-R2 receptors. Like the patch-clamp studies, secretion experiments demonstrated that both CNP and C-ANF are equally effective in reducing nicotine-evoked catecholamine secretion by cultured chromaffin cells, raising the possibility that the effect of CNP is predominantly mediated by the ANF-R2 and not the ANF-R1C receptors. Finally, this response appears to be specific to nicotinic agonists because neither histamine- nor KCl induced secretions were affected by natriuretic peptides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861138 TI - A possible role of glutathione as an endogenous agonist at the N-methyl-D aspartate recognition domain in rat brain. AB - Glutathione, both reduced (GSH) and oxidized (GSSG), was effective in displacing binding of L-[3H]-glutamic acid (L-[3H]Glu) and DL-(E)-2-[3H]amino-4-propyl-5 phosphono-3- pentenoic acid ([3H]CGP-39653) in rat brain synaptic membranes, with less potent displacement of binding of DL-alpha-amino-3-hydroxy-5-[3H] methylisoxazole-4-propionic and [3H]kainic acids. Liquid chromatographic analysis revealed that both GSH and GSSG were contaminated with L-Glu by < 1%. Both GSH and GSSG potentiated (+)-5-[3H]methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten 5,10-imine ([3H]MK-801) binding in a manner similar to that found with L-Glu. Pretreatment with glutamate dehydrogenase (GDH) induced a marked rightward shift of the concentration-response curve for L-Glu in the presence of NAD without affecting that in its absence, whereas GDH was ineffective in affecting the potentiation by both GSH and GSSG even in the presence of NAD. In the presence of GSH at a maximally effective concentration, both glycine (Gly) and spermidine potentiated [3H]MK-801 binding to a some-what smaller extent than that found in the presence of L-Glu at a maximally effective concentration. The potentiation of [3H]MK-801 binding by GSH was invariably attenuated by addition of CGP-39653, D-2 amino-5-phosphonovaleric acid (D-AP5), and 5,7-dichlorokynurenic acid (DCKA), whereas GSH was effective in diminishing potencies of CGP-39653, D-AP5, DCKA, and 6,7-dichloroquinoxaline-2,3-dione to inhibit [3H]MK-801 binding when determined in the presence of both L-Glu and Gly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861139 TI - Facilitation of hippocampal potentials by suramin. AB - The influence of suramin, a suggested purino-receptor antagonist, on the evoked synaptic potentials recorded from hippocampal slices was evaluated. The suramin induced a nondecremental, concentration-dependent amplification of the slope of excitatory postsynaptic potential and magnitude of the population spike (long term potentiation, LTP). The effect of suramin was completely abolished by adenylimidodiphosphate, a non-hydrolyzable analogue of ATP, and markedly reduced by NMDA-receptor antagonists DL-2-amino-5-phosphonovaleric acid and MK-801. These results indicate that, in addition to acting as an antagonist of P2 receptors, suramin is also able to facilitate hippocampal potentials in a way that involves mechanisms participating in induction of LTP. PMID- 7861140 TI - Morphine tolerance and physical dependence: reversal of opioid inhibition to enhancement of cyclic AMP formation. AB - This laboratory has previously demonstrated that the mu-selective opiate receptor agonist sufentanil can produce a naloxone-reversible increase or decrease in the stimulated formation of cyclic AMP (cAMP) in the myenteric plexus, depending on the concentration of opioid used. On the basis of these results, it was suggested that mu-opiate receptors are positively as well as negatively coupled to adenylyl cyclase. In the present study, the effect of chronic morphine exposure, in vivo, on the magnitude of electrically stimulated formation of cAMP and its modulation by sufentanil was investigated. In chronic morphine-treated preparations, the magnitude of electrically stimulated cAMP formation, while in the presence of an inhibitory (10(-6) M) concentration of sufentanil, is indistinguishable from the formation that occurs in opiate-naive preparations (in the absence of exogenous opioid). This indicates that the negative modulation of stimulated enteric cAMP formation by sufentanil manifests tolerance. Paradoxically, however, in "addicted tissue" the magnitude of the increase in cAMP formation produced by electrical stimulation in the presence of a previously inhibitory concentration of sufentanil is significantly larger than in its absence. Thus, the equivalence between the magnitude of stimulation-induced increase in cAMP formation observed in naive versus tolerant/dependent tissue, while in the presence of sufentanil, is due to the ability of an originally inhibitory concentration of opioid to enhance or facilitate stimulated formation of cAMP. It is suggested that tolerance/dependence to the opioid inhibition of stimulated cAMP formation results not only from the loss of inhibitory potency but also from its reversal to enhancement. PMID- 7861141 TI - Pertussis toxin-sensitive G protein alpha-subunits: production of monoclonal antibodies and detection of differential increases on differentiation of PC12 and LA-N-5 cells. AB - Monoclonal antibodies were produced that are specific for the three major pertussis toxin-sensitive G protein alpha-subunits present in mammalian brain- alpha o, alpha i1, and alpha i2--using purified bovine brain G proteins, purified rat brain G proteins, and purified recombinant alpha i2, respectively. These monoclonal antibodies were used to monitor changes in the concentrations of the three G protein alpha-subunits during differentiation of PC12 cells and human neuroblastoma LA-N-5 cells. In PC12 cells, levels of alpha i1 but not alpha i2 increased during nerve growth factor-induced differentiation. In contrast, alpha i2 but not alpha i1 increased when LA-N-5 cells were differentiated with retinoic acid. The concentration of alpha o increased in both cell lines during differentiation. Electrophoretic resolution of alpha o subtypes revealed that although alpha o2 was the major subtype in undifferentiated cells, only the concentration of alpha o1 increased during differentiation of both PC12 and LA-N 5 cells. The level of 43-kDa growth-associated protein, a protein known to associate with alpha o, increased similarly to that of alpha o1. ADP-ribosylation of alpha o, alpha i1, and alpha i2 with pertussis toxin did not alter the reactivities of the monoclonal antibodies, but toxin treatment of cells reduced the concentrations of each protein after 24 h. There was no change in the concentration of alpha q, which is not ADP-ribosylated by pertussis toxin. Thus, these new monoclonal antibodies enabled the detection of differential increases in subtypes of alpha i and alpha o associated with neuronal differentiation. PMID- 7861142 TI - Effect of noradrenergic lesions on subtypes of alpha 2-adrenoceptors in rat brain. AB - The binding of [3H]rauwolscine to alpha 2A- (also referred to as alpha 2D-) and alpha 2C-adrenoceptors in homogenates of rat cerebral cortex was measured by exploiting the selectivity of oxymetazoline for alpha 2A-adrenoceptors. Inhibition of [3H]rauwolscine binding by oxymetazoline was modeled best assuming binding to two sites (p < 0.001). Competition curves for oxymetazoline were shifted rightward by the addition of GTP (250 microM) but were still fit best by a two-site model (p < 0.001). A concentration of oxymetazoline was calculated that would optimally antagonize [3H]rauwolscine binding (with GTP present) to oxymetazoline-sensitive alpha 2A-adrenoceptors, minimally inhibiting binding to alpha 2C-adrenoceptors. Subsequently, [3H]rauwolscine binding to alpha 2A- and alpha 2C-adrenoceptors in cortex was examined 3 weeks after destruction of noradrenergic terminals. Binding to alpha 2C-adrenoceptors was increased significantly after treatment with 6-hydroxydopamine, (6-OHDA) compared with vehicle-treated controls, whereas binding to alpha 2A-adrenoceptors was unchanged. Pretreatment of rats with desipramine before 6-hydroxydopamine, to protect noradrenergic neurons, resulted in no changes in binding to either alpha 2A- or alpha 2C-adrenoceptors. Thus, alpha 2C-adrenoceptors are regulated by changes in synaptic availability of norepinephrine. alpha 2A-Adrenoceptors are either not regulated by synaptic norepinephrine or are located both post- and presynaptically so that up-regulation of postsynaptic alpha 2A-adrenoceptors is offset by a loss of presynaptic alpha 2A-adrenoceptors. PMID- 7861143 TI - N-terminal-specific anti-B-50 (GAP-43) antibodies inhibit Ca(2+)-induced noradrenaline release, B-50 phosphorylation and dephosphorylation, and calmodulin binding. AB - B-50 (GAP-43) is a presynaptic protein kinase C (PKC) substrate implicated in the molecular mechanism of noradrenaline release. To evaluate the importance of the PKC phosphorylation site and calmodulin-binding domain of B-50 in the regulation of neurotransmitter release, we introduced two monoclonal antibodies to B-50 into streptolysin O-permeated synaptosomes isolated from rat cerebral cortex. NM2 antibodies directed to the N-terminal residues 39-43 of rat B-50 dose-dependently inhibited Ca(2+)-induced radiolabeled and endogenous noradrenaline release from permeated synaptosomes. NM6 C-terminal-directed (residues 132-213) anti-B-50 antibodies were without effect in the same dose range. NM2 inhibited PKC-mediated B-50 phosphorylation at Ser41 in synaptosomal plasma membranes and permeated synaptosomes, inhibited 32P-B-50 dephosphorylation by endogenous synaptosomal phosphatases, and inhibited the binding of calmodulin to synaptosomal B-50 in the absence of Ca2+. Similar concentrations of NM6 did not affect B-50 phosphorylation or dephosphorylation or B-50/calmodulin binding. We conclude that the N-terminal residues 39-43 of the rat B-50 protein play an important role in the process of Ca(2+)-induced noradrenaline release, presumably by serving as a local calmodulin store that is regulated in a Ca(2+)- and phosphorylation dependent fashion. PMID- 7861144 TI - Effects of internal pH on the acetylcholine transporter of synaptic vesicles. AB - Uptake of acetylcholine (ACh) by synaptic vesicles isolated from the electric organ of Torpedo was induced with an artificially imposed proton gradient. The gradient was formed by hyposmotic lysis and resealing of vesicles in a low pH buffer to form vesicular ghosts followed by sudden elevation of the pH of the ghost suspension. [3H]ACh accumulated rapidly, the proton gradient collapsed spontaneously within 5 min as monitored by [14C]methylamine uptake, and the accumulated ACh leaked out of the ghosts after 5 min. Vesamicol blocked both uptake and efflux of the [3H]ACh, demonstrating that both processes are mediated by the ACh transporter. The protonophore nigericin also blocked uptake very potently. Specific uptake was titrated with variable concentrations of [3H]ACh. It exhibited Km and Vmax values of approximately 200-500 microM and 7-30 nmol [3H]ACh/mg at 5 min, respectively, which are values close to those commonly observed for ATP-dependent uptake by intact vesicles. Specific uptake by ghosts was titrated with variable internal pH and constant external pH. It exhibited maximal uptake between internal pH 4.5 and 5.5. The dependence was very steep and could be fit best by assuming that the active form of the transporter requires protonation of two internal sites of apparent pK value of 5.3 +/- 0.2. A similar result was obtained when the uptake was titrated with variable internal pH with a constant thermodynamic driving force maintained by keeping the external pH approximately 2.6 units higher. The origin of the transport inhibition that sets in at very low internal pH values is not clear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861145 TI - Muscarinic cholinoceptor-stimulated synthesis and degradation of inositol 1,4,5 trisphosphate in the rat cerebellar granule cell. AB - A detailed analysis of the generation and subsequent metabolism of inositol 1,4,5 trisphosphate [Ins(1,4,5)P3] following muscarinic cholinoceptor stimulation in primary cultures of rat cerebellar granule cells has been undertaken. Following incubation of cerebellar granule cell cultures with [3H]inositol for 48 h, labelling of the inositol phospholipid pool approached equilibrium. Significant basal labelling of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6), as well as inositol mono- to tetrakisphosphate, fractions was observed. Addition of carbachol (1 mM) caused an immediate increase in level of Ins(1,4,5)P3 (peak increase two-fold over basal by 60 s), which was well-maintained over the initial 300 s following agonist addition. In contrast, only a modest, more slowly developing, increase in inositol tetrakisphosphate accumulation was observed, whereas labelling of InsP5 and InsP6 was entirely unaffected by carbachol stimulation. Analysis of the products of Ins(1,4,5)P3 and inositol 1,3,4,5-tetrakisphosphate metabolism in broken cell preparations strongly suggested that Ins(1,4,5)P3 metabolism occurs predominantly via the inositol polyphosphate 5-phosphatase route, with metabolism via the Ins(1,4,5)P3 3-kinase being a relatively minor pathway. In view of the pattern of inositol (poly)phosphate metabolites observed on stimulation of the muscarinic receptor, it seems likely that, over the time course studied, the inositol polyphosphates are derived principally from phosphoinositide-specific phospholipase C hydrolysis of phosphatidylinositol 4,5-bisphosphate, although some hydrolysis of phosphatidyl-inositol 4-phosphate cannot be excluded. PMID- 7861146 TI - Modulation of glutamate and aspartate release from slices of hippocampal area CA1 by inhibitors of arachidonic acid metabolism. AB - Slices of hippocampal area CA1 were used to test inhibitors of arachidonic acid metabolism for their effects on glutamate/aspartate release from the CA3-derived Schaffer collateral, commissural, and ipsilateral associational terminals. Test compounds [3 microM nordihydroguaiaretic acid (NDGA) and 1 microM 3-[3-(4 chlorobenzyl)-3-tert-butylthio-5- isopropylindol-2-yl]-2,2-dimethyl-propanoic acid (MK-886)] that reduced the production and release of 5-lipoxygenase metabolites also selectively reduced the K(+)-evoked release of aspartate. In contrast, the cyclooxygenase inhibitor indomethacin (100 microM) selectively enhanced the release of glutamate. At a concentration (100 microM) that nonselectively depressed the release of arachidonic acid and its metabolites, NDGA markedly depressed the release of aspartate, glutamate, and GABA. An inhibitor of the 12-lipoxygenase and an inhibitor of nitric oxide synthase did not affect the K(+)-evoked release of any transmitter amino acid. These results suggest that a 5-lipoxygenase product selectively enhances aspartate release and a cyclooxygenase product selectively depresses glutamate release. They are also consistent with previous evidence that arachidonic acid and/or platelet activating factor enhances the release and depresses the uptake of glutamate and aspartate. The K(+)-evoked release of excitatory amino acids is much more sensitive to modulation by lipid mediators than is GABA release. Activation of NMDA receptors may enhance the K(+)-evoked release of glutamate and aspartate from CA1 slices by stimulating the production and release of lipid modulators. PMID- 7861147 TI - Effects of amphetamine on carrier-mediated and electrically stimulated dopamine release in slices of rat caudate putamen and nucleus accumbens. AB - The effects of (+)-amphetamine on carrier-mediated and electrically stimulated dopamine release were investigated using fast cyclic voltammetry in rat brain slices incorporating the nucleus accumbens, and in the caudate putamen. In the caudate putamen, dopamine release either increased with increasing frequency of local electrical stimulation (hot spots) or did not increase significantly (cold spots); dopamine release increased with increasing frequency of electrical stimulation in the nucleus accumbens. Local pressure application of (+) amphetamine from a micropipette caused dopamine efflux at all sites examined, and this was not affected by sulpiride, indicating that efflux of dopamine caused by (+)-amphetamine is not regulated by dopamine D2 autoreceptors. (+)-Amphetamine reduced single-pulse electrically stimulated dopamine release at all sites; sulpiride reversed this decrease, indicating that endogenous dopamine released by (+)-amphetamine activates dopamine D2 autoreceptors. In nucleus accumbens and hot spots, (+)-amphetamine did not affect 20-pulse 50-Hz-stimulated dopamine release, whereas in cold spots it potentiated 20-pulse 50-Hz-stimulated dopamine release. We conclude that (+)-amphetamine modifies electrically stimulated dopamine release by uptake inhibition or by indirect activation of D2 autoreceptors; the precise mechanism is determined by site and duration of electrical stimulation. PMID- 7861148 TI - Mechanism underlying the ATP-induced increase in the cytosolic Ca2+ concentration in chick ciliary ganglion neurons. AB - We examined the mechanism underlying the ATP-induced increase in the cytosolic Ca2+ concentration ([Ca]in) in acutely isolated chick ciliary ganglion neurons, using fura-2 microfluorometry. The ATP-induced increase in [Ca]in was dependent on external Ca2+, was blocked in a dose-dependent manner by reactive blue 2, and was substantially inhibited by both L- and N-type Ca2+ channel blockers. ATP was effective in increasing [Ca]in in the presence of a desensitizing concentration of nicotine (100 microM), and simultaneous addition of maximal doses of ATP and nicotine caused an additive increase in [Ca]in, suggesting that ATP acts on a site distinct from nicotinic acetylcholine receptors. ATP also increased the cytosolic Na+ concentration as determined by sodium-binding benzofuran isophthalate microfluorometry. These results suggest that ATP increases Na+ influx through P2 purinoceptor-associated channels resulting in membrane depolarization, which in turn increases Ca2+ influx through voltage-dependent Ca2+ channels. However, ATP still caused a small increase in [Ca]in under Na+ free conditions, and this [Ca]in increase was little affected by Ca2+ channel blockers. ATP also increased Mn2+ influx under Na+-free conditions, as indicated by quenching of fura-2 fluorescence. These results suggest that nonselective cationic channels activated by ATP are permeable not only to Ca2+ but also to Mn2+, in addition to monovalent cations. PMID- 7861149 TI - Mobilization of inositol 1,4,5-trisphosphate-sensitive Ca2+ stores supports bradykinin- and muscarinic-evoked release of [3H] noradrenaline from SH-SY5Y cells. AB - The human neuroblastoma cell line SH-SY5Y, maintained at confluence for 14 days, released [3H]-noradrenaline ([3H]NA) when stimulated with either the muscarinic receptor agonist methacholine or bradykinin. The major fraction of release was rapid, occurring in < 10 s, whereas nicotine-evoked release was slower. When the extracellular [Ca2+]e) was buffered to approximately 50-100 nM, release evoked by nicotine was abolished, whereas that in response to methacholine or bradykinin was reduced by approximately 50% with EC50 values of -5.46 +/- 0.05 M and -7.46 +/- 0.06 M (log 10), respectively. Methacholine and bradykinin also produced rapid elevations of both inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and intracellular free [Ca2+] ([Ca2+]i). These elevations were reduced at low [Ca2+]e and under these conditions the EC50 values for peak elevation of [Ca2+]i were 6.00 +/- 0.14 M for methacholine and -7.95 +/- 0.34 M for bradykinin (n = 3 for all EC50 determinations). At low [Ca2+]e, depletion of nonmitochondrial intracellular Ca2+ stores with the Ca(2+)-ATPase inhibitor thapsigargin produced a transient small elevation of [Ca2+]i and a minor release of [3H]NA. At low [Ca2+]e, thapsigargin abolished elevation of [Ca2+]i in response to methacholine and bradykinin and completely inhibited their stimulation of [3H]NA release. It is proposed, therefore, that Ca2+ release from Ins (1,4,5)P3-sensitive stores is a major trigger of methacholine- and bradykinin-evoked [3H]NA release in SH-SY5Y cells. PMID- 7861150 TI - Neurotoxin quinolinic acid is selectively elevated in spinal cords of rats with experimental allergic encephalomyelitis. AB - Experimental allergic encephalomyelitis (EAE) is an autoimmune, animal model of multiple sclerosis (MS) in which demyelination and paralysis are evident. Quinolinic acid (QUIN) is a neurotoxin and endogenous N-methyl-D-aspartate receptor agonist formed from tryptophan. The role of neurotoxins in general and QUIN in particular in EAE or MS is unknown. Lewis rats inoculated with myelin basic protein developed signs of EAE by day 12, were killed, and their tissues assayed for QUIN by gas chromatography with mass spectrometry. QUIN levels were significantly elevated in the more caudal regions of the spinal cords of animals with EAE. Brain, serum, and liver levels of QUIN were not altered. In a similar manner, QUIN in mylin basic protein-injected, asymptomatic animals was not different from control animals. The time course for QUIN was similar to the neurological signs of the disorder; however, the initial elevation in QUIN occurred before the appearance of behavioral signs. Last, treatment with the glucocorticoid dexamethasone prevented both the signs of EAE and the elevation in spinal cord QUIN. It is not known whether QUIN contributes to the paralysis in EAE. However, if QUIN is pathogenic in EAE this finding could have therapeutic implications for MS. PMID- 7861151 TI - [3H]paroxetine binding is altered in the hippocampus but not the frontal cortex or caudate nucleus from subjects with schizophrenia. AB - [3H]Paroxetine binding to particulate membrane from tissue, obtained at autopsy, from the hippocampus, frontal cortex, and caudate nucleus from subjects who had or had not had schizophrenia was measured. The density of [3H]paroxetine binding to membranes from subjects who had or had not had schizophrenia did not differ. Similarly, the affinity of [3H]paroxetine binding in the frontal cortex and caudate nucleus was not different. By contrast, the affinity of [3H]paroxetine binding to hippocampal membrane from subjects who had schizophrenia was significantly lower than the affinity of binding for the nonschizophrenic subjects (0.40 +/- 0.06 vs. 0.26 +/- 0.02; p < 0.05). As [3H]paroxetine binds to the serotonin transporter, these data suggest that the serotonin transporter is altered in the hippocampus in subjects with schizophrenia. PMID- 7861152 TI - Protection and potentiation of 1-methyl-4-phenylpyridinium-induced toxicity by cytochrome P450 inhibitors and inducer may be due to the altered uptake of the toxin. AB - Earlier studies from our laboratory have demonstrated that 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) toxicity could be modulated by inhibitors and inducer of cytochrome P450 (P450) in an in vitro model consisting of sagittal slices of mouse brain. To understand the molecular mechanisms underlying the role of P450 on MPTP toxicity, it was undertaken to study the effect of the modulators of P450 on the toxicity of the metabolite of MPTP, namely, 1-methyl-4 phenylpyridinium ion (MPP+). Incubation of mouse brain slices with various concentrations of MPP+ (1-100 microM) resulted in dose-dependent inhibition of mitochondrial enzyme NADH-dehydrogenase (NADH-DH) and leakage of the cytosolic enzyme lactate dehydrogenase from the slice into the medium. MPP(+)-induced toxicity was abolished by pretreatment of the slices with inhibitors of monoamine oxidase (MAO; pargyline and deprenyl) or inhibitors of P450 (piperonyl butoxide or SKF-525A) or dopamine uptake blocker (GBR-12909), as measured by the activity of NADH-DH in slices and leakage of lactate dehydrogenase from the slice into the medium. Slices prepared from mice pretreated with phenobarbital (an inducer of P450) potentiated the toxic effects of MPP+. Pretreatment of slices with MAO inhibitor, P450 inhibitors, or dopamine uptake blocker attenuated the uptake of MPP+ into the slices. In contrast, MPP+ uptake was significantly increased in slices prepared from phenobarbital-pretreated mice. Thus, both MAO and P450 inhibitors abolish the toxicity of MPP+ in the sagittal slices of mouse brain by altering the uptake of the toxin into the slices. PMID- 7861153 TI - Tau self-association: stabilization with a chemical cross-linker and modulation by phosphorylation and oxidation state. AB - tau is a major component of paired helical filaments found in the neurofibrillary tangles of Alzheimer's diseased brain. However, the mechanism or mechanisms responsible for the association of tau to form these aggregates remains unknown. In this study, the role of intermolecular disulfide bonds in the formation of higher order oligomers of bovine tau and the human recombinant tau isoform T3 was examined using the chemical cross-linking agent disuccinimidylsuberate (DSS). In addition, the role of phosphorylation and oxidation state on the in vitro self association of tau was studied using this experimental model. Stabilization of tau-tau interactions with DSS indicated that intermolecular disulfide bonds probably play a predominant role in dimer formation, but the formation of higher order oligomers of tau cannot be attributed to these bonds alone. tau-tau interactions were significantly decreased either by blocking Cys residues or by exposing the tau to a reducing (nitrogen and dithiothreitol), instead of an oxidizing, environment. tau self-association was also significantly decreased by prior phosphorylation with calcium/calmodulin-dependent protein kinase II. Phosphorylation by cyclic AMP-dependent protein kinase or dephosphorylation by alkaline phosphatase did not alter tau self-assembly. These data suggest a role for several factors that may modulate tau self-association in vivo. PMID- 7861154 TI - Decreased catalase activity but unchanged superoxide dismutase activity in brains of patients with dementia of Alzheimer type. AB - "Oxidative stress" may be of significance in the etiopathogenesis of dementia of Alzheimer type (DAT). Therefore, we measured activities of the enzymes superoxide dismutase (SOD) and catalase (CAT), which detoxicate reactive oxygen species. Enzyme activities were measured postmortem in basal ganglia, cortical, and limbic brain regions of patients with DAT and age-matched controls. SOD activity increased with age in basal nucleus of Meynert. However, there was no significant difference in SOD activity between DAT and controls. CAT activity was independent of age and postmortem time. There were significant reductions in CAT activity in parietotemporal cortex, basal ganglia, and amygdala in DAT compared with controls (p < 0.05 to 0.01). Our findings are in line with the assumption that reactive oxygen species could contribute to the pathogenesis of DAT. Absence of these changes in basal nucleus of Meynert might reflect retrograde degeneration of cholinergic fibers. PMID- 7861155 TI - Validation of a noninvasive method to measure brain temperature in vivo using 1H NMR spectroscopy. AB - The goal of this study was to evaluate the potential of using the difference between the 1H NMR frequencies of water and N-acetylaspartic acid (NAA) to measure brain temperature noninvasively. All water-suppressed and non-water suppressed 1H NMR spectra were obtained at a field strength of 4.7 T using a surface coil. Experiments performed on model solutions revealed a decrease in the difference between NMR frequencies for NAA and water as a linear function of increasing temperature from 14 to 45 degrees C. Changing pH in the range 5.5-7.6 produced no discernible trends for concurrent changes in the slope and intercept of the linear relationship. There were minor changes in slope and intercept for solutions containing 80 or 100 mg of protein/ml versus no protein, but these changes were not considered to be of sufficient magnitude to deter the use of this approach to measure brain temperature. The protein content of swine cerebral cortex was found to remain constant from newborn to 1 month old (78 +/- 12 mg/g; n = 41). Therefore, data collected for the model solution containing 80 mg of protein/ml were used as a calibration curve to calculate brain temperature in eight swine during control, hypothermia, ischemia, postischemia, or death, over a temperature range of 23-40 degrees C. A plot of 61 temperatures determined from 1H NMR versus temperatures measured from an optical fiber probe sensor implanted 1 cm into the cerebral cortex showed excellent linear agreement (slope = 1.00 +/- 0.03, r2 = 0.96). We conclude that 1H NMR spectroscopy presents a practical means of making noninvasive measurements of brain temperature with an accuracy of better than +/- 1 degree C. PMID- 7861156 TI - Altered neurotrophin mRNA levels in peripheral nerve and skeletal muscle of experimentally diabetic rats. AB - The levels of neurotrophin mRNA in sensory ganglia, sciatic nerve, and skeletal muscle were measured in the streptozotocin-diabetic rat using northern blotting. Periods of diabetes of 4, 6, and 12 weeks significantly elevated brain-derived neurotrophic factor (BDNF) mRNA levels in soleus muscle compared with age-matched controls, the increase being highest at 6 weeks. At all time periods studied, the levels of nerve growth factor (NGF) mRNA in soleus muscle were decreased by 21 47%. Following 12 weeks of diabetes, BDNF mRNA levels were increased approximately two- to threefold in L4 and L5 dorsal root ganglia (DRG), and in sciatic nerve, NGF mRNA levels were raised 1.65-fold. Intensive insulin treatment of diabetic rats for the final 4 weeks of the 12-week period of diabetes reversed the up-regulation of BDNF mRNA in DRG and muscle and NGF mRNA in sciatic nerve. All diabetes-induced changes in neurotrophin mRNA were not paralleled by similar alterations in the levels of beta-actin mRNA in muscle and nerve, or of GAP-43 mRNA in DRG and nerve. It is proposed that the up-regulation of neurotrophin mRNA is an endogenous protective and/or repair mechanism induced by insult and, as such, appears as an early marker of peripheral nerve and muscle damage in experimental diabetes. PMID- 7861157 TI - The proteins synaptotagmin and syntaxin are not general targets of Lambert-Eaton myasthenic syndrome autoantibody. AB - Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neuromuscular disease in which impairment of Ca2+ entry into the nerve ending and consequent impaired release of acetylcholine (ACh) results in muscle weakness. The identity of the primary antigenic target molecule(s) of the autoantibodies is uncertain. Electrophysiological studies and 45Ca2+ uptake studies implicate a direct effect on the Ca2+ channel complex at the motor nerve terminal. Some recent studies, however, suggest a more indirect interference caused by binding of autoantibodies to synaptotagmin or syntaxin, molecules presumed to be involved in docking and/or coupling the synaptic vesicles to the Ca2+ channels in the active zone for vesicle exocytosis and transmitter release. Western blot analyses of rat and human brain membrane proteins and pure recombinant synaptotagmin and syntaxin were used to examine directly the targets of LEMS autoantibodies and determine specifically whether or not synaptotagmin and/or syntaxin were general targets in LEMS. IgG from 14 patients with LEMS was used to probe western blots of gels containing synaptotagmin, syntaxin, rat synaptosomal proteins, and human brain membrane proteins. Several similar immunoreactive bands were observed using both rat and human brain membranes. These include high-molecular-weight protein bands whose size would be consistent with being components of Ca2+ channels. No reactive component was observed against either syntaxin or synaptotagmin in IgG of the 14 LEMS patients. However, both human and rat brain membranes contain proteins recognized by antibodies directed against synaptotagmin or syntaxin, indicating their immunologic relatedness and evolutionary conservation. These results suggest that large-molecular-weight proteins consistent with being Ca2+ channel subunits rather than syntaxin and synaptotagmin are general targets of LEMS autoantibodies. PMID- 7861158 TI - Inhibition of neutral amino acid transport across the human blood-brain barrier by phenylalanine. AB - The delivery of large neutral amino acids (LNAAs) to brain across the blood-brain barrier (BBB) is mediated by the L-type neutral amino acid transporter present in the membranes of the brain capillary endothelial cell. In experimental animals, the L-system transporter is saturated under normal conditions, and therefore an elevation in the plasma concentration of one LNAA will reduce brain uptake of others. In this study, we used positron emission tomography (PET) to determine the effect of elevated plasma phenylalanine concentrations on the uptake of an artificial neutral amino acid, [11C]-aminocyclohexanecarboxylate ([11C]ACHC), in human brain. PET scans were performed on six normal male subjects after an overnight fast and again 60 min after oral administration of 100 mg/kg of phenylalanine. The plasma phenylalanine concentration increased by an average of 11-fold between the first and second scans. This increase produced a reduction in [11C]ACHC uptake in all brain regions but not in scalp. The mean +/- SD influx rate constant for whole brain decreased after phenylalanine ingestion from 0.036 +/- 0.002 to 0.019 +/- 0.004 ml/g/min. Kinetic analysis of the effect of plasma phenylalanine concentration on the rate of [11C]ACHC uptake is compatible with a model of competitive inhibition so that large increases in the concentration of one LNAA in plasma will reduce the brain uptake of other LNAAs across the human BBB. PMID- 7861159 TI - Localization of various forms of the gamma subunit of G protein in neural and nonneural tissues. AB - For a study of the localization of various forms of the gamma subunit of G proteins, antibodies were raised in rabbits against peptides that corresponded to partial amino acid sequences of bovine gamma 2, gamma 3, gamma 5, and gamma 7. Affinity-purified antibodies against gamma 2, gamma 3, and gamma 5 reacted specifically with gamma 2, gamma 3, and gamma 5, respectively, but the antibody against gamma 7 reacted with gamma 2, gamma 3, and a novel gamma subunit, designated gamma S1, as well as with gamma 7. Because these antibodies reacted with the respective forms of the gamma subunit from rat brain, we investigated the localization of gamma subunits in the rat. gamma 2 and gamma 3 were abundant in all regions in the brain, whereas the concentration of gamma 5 and gamma 7 was relatively low with the single exception being a high concentration of gamma 7 in the striatum. The concentration of gamma 2 was consistently high during ontogenic development in the rat brain, whereas gamma 3 appeared about a week after birth and their concentrations then increased until a month after birth. In tissues other than the brain, gamma 3 was observed only in the pituitary gland, whereas gamma 2, gamma 5, and gamma 7 were found in a variety of tissues. In addition, most tissues contained relatively high concentrations of some other gamma subunit, which was detected with an antibody against a gamma 7-derived peptide and appeared to be gamma S1. Among cloned cells tested, gamma 3 was detected only in PC12 pheochromocytoma cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861160 TI - A UDP-sugar pyrophosphatase is developmentally regulated in the rat retina. AB - Rat retina tissue contains relatively high amounts of GD3 in relation to ganglio series gangliosides even in the adult stages. This was attributed in part to an activity ratio between the enzyme that converts GM3 to GD3 [sialytransferase II (ST-II)] and the enzyme that converts GM3 to GM2 [N acetylgalactosaminyltransferase (GalNAc-T)] favorable to ST-II. Here we report the presence in the rat retina tissue of an activity that hydrolyzes one of the substrates of GalNAc-T, the donor sugar nucleotide UDP-GalNAc. Chromatographic analyses of the products of degradation indicate that the activity corresponds to a UDP-sugar pyrophosphatase/phosphodiesterase I. The activity is developmentally regulated, increasing after day 4 of postnatal development to reach values approximately 10-fold higher in the adult tissue. The activity sediments with the microsomal membranes, also hydrolyzes UDP-Gal, does not hydrolyze CMP-NeuNAc, requires Mn2+, and does not require detergent. Kinetic data showed that the same activity hydrolyzes UDP-GalNAc and UDP-Gal, each one acting as competitive inhibitor for the hydrolysis of the other (Km and Ki for UDP-GalNAc, 48 and 33 microM, respectively; Km and Ki for UDP-Gal, 5 and 12 microM, respectively). In another set of experiments, it was found that the activities of the GalNAc-T and the enzyme that converts GM2 to GM1 [galactosyltransferase II (Gal T-II)] increased about threefold from birth to day 4 and then decreased to stabilize by day 6 in values that were similar to those at birth and about one-half those of ST-II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861161 TI - Accumulation of enkephalin, proenkephalin mRNA, and neuropeptide Y in immunologically denervated rat adrenal glands: evidence for divergent peptide regulation. AB - To investigate transsynaptic effects on peptides of adrenal chromaffin cells in the rat, presynaptic sympathetic terminals were destroyed by intravenous injection of monoclonal antibodies to acetylcholinesterase. At several times thereafter, neuropeptide Y (NPY)-like immunoreactivity (NPY-IR) and methionine enkephalin-like immunoreactivity (Met-Enk-IR) were measured by radioimmunoassay. Within 2 days of antibody injection, adrenal Met-Enk-IR increased five- to 10 fold and NPY-IR increased 50%. These effects were accompanied by large increases in proenkephalin A mRNA assayed by polymerase chain reaction. The peptide responses could reflect either an acute activation, as presynaptic terminals degenerated, or a chronic synaptic inactivation after terminal degeneration. To test the possibilities, muscarinic and nicotinic receptors were inhibited by repeated injection of atropine (1 mg/kg) and chlorisondamine (5 mg/kg). Measurements of urinary free catecholamine excretion showed that this treatment prevented the paroxysmal release of norepinephrine and reduced the release of epinephrine that normally followed injection of acetylcholinesterase antibodies. When the drugs were given alone for 2 or 4 days, adrenal Met-Enk-IR increased modestly and NPY-IR remained steady or declined. When given together with acetylcholinesterase antibodies, the cholinergic antagonists blocked the increase of NPY-IR but not Met-Enk-IR. Adding naloxone (1 mg/kg) to the treatment regimen enhanced the blockade of epinephrine excretion and largely prevented the antibody induced increase in Met-EnK-IR. These findings indicate that adrenal NPY and enkephalin are not regulated identically. Adrenal NPY behaves as though controlled by transsynaptic cholinergic input. On the other hand, adrenal enkephalin may be regulated by additional or different mechanisms, possibly involving peptidergic transmission or synaptic inactivation. PMID- 7861162 TI - DMAP-85: a tau-like protein from Drosophila melanogaster larvae. AB - Microtubule-associated proteins (MAPs) play major regulatory roles in the organization and integrity of the cytoskeletal network. Our main interest in this study was the identification and the analysis of structural and functional aspects of Drosophila melanogaster MAPs. A novel MAP with a relative molecular mass of 85 kDa from Drosophila larvae was found associated with taxol-polymerized microtubules. In addition, this protein bound to mammalian tubulin in an overlay assay and coassembled with purified bovine brain tubulin in microtubule sedimentation experiments. The estimated stoichiometry of 85-kDa protein versus tubulin in the polymers was 1:5.3 +/- 0.2 mol/mol. It was shown that the 85-kDa protein bound specifically to an affinity column of Sepharose-beta II-(422-434) tubulin peptide, which contains the sequence of the MAP binding domain on beta II tubulin. Affinity-purified 85-kDa protein enhanced microtubule assembly in a concentration-dependent manner. This effect was significantly decreased by the presence of the beta II-(422-434) peptide in the assembly assays, thus confirming the specificity of the 85-kDa protein interaction with the C-terminal domain on tubulin. Furthermore, this protein also exhibited a strong affinity for calmodulin, based on affinity chromatographic assays. Monoclonal and polyclonal anti-tau antibodies, including sequence-specific probes that recognize repeated microtubule-binding motifs on tau, MAP-2, and MAP-4 and specific N-terminal sequences of tau, cross-reacted with the 85-kDa protein from Drosophila larvae. These results suggest that tau and Drosophila 85-kDa protein share common functional and structural epitopes. We have named this protein as DMAP-85 for Drosophila MAP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861163 TI - Monoclonal antibodies to the human gamma 2 subunit of the GABAA/benzodiazepine receptors. AB - The large intracellular loop (IL) of the gamma 2 subunit of the cloned human gamma-aminobutyric acidA (GABAA) receptor (gamma 2 IL) was expressed in bacteria as glutathione-S-transferase and staphylococcal protein A fusion proteins. Mice were immunized with the fusion proteins (one protein per animal), and monoclonal antibodies were obtained. Six monoclonal antibodies reacted with the gamma 2 IL moiety of the fusion proteins. Three of these monoclonal antibodies also immunoprecipitated a high proportion of the GABAA/benzodiazepine receptors from bovine and rat brain and reacted with a wide 44,000-49,000-M(r) peptide band in immunoblots of affinity-purified GABAA receptors. These monoclonal antibodies are valuable reagents for the molecular characterization of the GABAA receptors in various brain regions. PMID- 7861164 TI - Synthesis of serotonin in traumatized rat brain. AB - Previous studies have demonstrated that focal freezing lesions in rats cause a widespread decrease of cortical glucose use in the lesioned hemisphere and this was interpreted as a reflection of depression of cortical activity. The serotonergic neurotransmitter system was implicated in these alterations when it was shown that (1) cortical serotonin metabolism was increased widely in focally injured brain and (2) inhibition of serotonin synthesis prevented the development of cortical hypometabolism. In the present studies we applied an autoradiographic method that uses the accumulation of the 14C-labeled analogue of serotonin alpha methylserotonin to assess changes in the rate of serotonin synthesis in injured brain. The results confirmed that 3 days after the lesion was made, at the time of greatest depression of glucose use, serotonin synthesis was significantly increased in cortical areas throughout the injured hemisphere. The increase was also seen in the dorsal hippocampus and area CA3, as well as in the medial geniculate and dorsal raphe, but not in any other subcortical structures including median raphe. Present results suggest that the functional changes in the cortex of the lesioned hemisphere are associated with an increased rate of serotonin synthesis mediated by activation of the dorsal raphe. We also documented by alpha-[14C]aminoisobutyric acid autoradiography that there was increased permeability of the blood-brain barrier, but this was restricted to the rim of the lesion. PMID- 7861165 TI - Evidence for D4 receptor regulation of retinomotor movement in isolated teleost cone inner-outer segments. AB - In the retinas of teleost fish, cone photoreceptors change shape in response to light and circadian signals. They elongate in the dark, contract in the light, and under conditions of constant darkness undergo appropriate movements at expected dusk and dawn. Dopamine induces cones to contract, thus mimicking the effect of light or expected dawn. To identify the receptor subtype responsible for mediating dopamine regulation of cone retinomotor movements, we have carried out pharmacological studies using isolated fragments of teleost cones consisting of cone inner segments-cone outer segments (CIS-COS). Isolated CIS-COS retain the ability to elongate in dark culture and contract when subsequently exposed to light or dopamine. We report that dark-induced elongation of CIS-COS was inhibited by dopamine and its agonists with an effectiveness ranking of dopamine = quinpirole > bromocriptine >>> SKF-38393. After 60 min of elongation in dark culture, CIS-COS myoids contracted when subsequently cultured in the dark with dopamine or quinpirole. Quinpirole-induced inhibition of elongation and quinpirole-induced contraction were completely blocked by clozapine at 1 microM or by sulpiride at 100 microM. These effectiveness profiles for dopamine agonists and antagonists suggest that dopamine regulation of cone retinomotor movement is mediated by a D4-like receptor. PMID- 7861166 TI - Dynamic measurements of cerebral pentose phosphate pathway activity in vivo using [1,6-13C2,6,6-2H2]glucose and microdialysis. AB - Cerebral pentose phosphate pathway (PPP) activity has been linked to NADPH dependent anabolic pathways, turnover of neurotransmitters, and protection from oxidative stress. Research on this potentially important pathway has been hampered, however, because measurement of regional cerebral PPP activity in vivo has not been possible. Our efforts to address this need focused on the use of a novel isotopically substituted glucose molecule, [1,6-13C2,6,6-2H2]glucose, in conjunction with microdialysis techniques, to measure cerebral PPP activity in vivo, in freely moving rats. Metabolism of [1,6-13C2,6,6-2H2]glucose through glycolysis produces [3-13C]lactate and [3-13C,3,3-2H2]lactate, whereas metabolism through the PPP produces [3-13C,3,3-2H2]lactate and unlabeled lactate. The ratios of these lactate isotopomers can be quantified using gas chromatography/mass spectrometry (GC/MS) for calculation of PPP activity, which is reported as the percentage of glucose metabolized to lactate that passed through the PPP. Following addition of [1,6-13C2,6,6-2H2]glucose to the perfusate, labeled lactate was easily detectable in dialysate using GC/MS. Basal forebrain and intracerebral 9L glioma PPP values (mean +/- SD) were 3.5 +/- 0.4 (n = 4) and 6.2 +/- 0.9% (n = 4), respectively. Furthermore, PPP activity could be stimulated in vivo by addition of phenazine methosulfate, an artificial electron acceptor for NADPH, to the perfusion stream. These results show that the activity of the PPP can now be measured dynamically and regionally in the brains of conscious animals in vivo. PMID- 7861167 TI - Participation of tubulin in the stimulatory regulation of adenylyl cyclase in rat cerebral cortex membranes. AB - This study examined effects of tubulin on the activation of adenylyl cyclase in rat cerebral cortex membranes. Tubulin, prepared from rat brain by polymerization with the hydrolysis-resistant GTP analogue 5'-guanylylimidodiphosphate (GppNHp) caused significant activation of the enzyme by approximately 156% under conditions in which stimulation rather than inhibition of the enzyme was favored. Tubulin-GppNHp activated isoproterenol-sensitive adenylyl cyclase, potentiated forskolin-stimulated activity of the enzyme, and reduced agonist binding affinity for beta-adrenergic receptors. When tubulin, polymerized with the hydrolysis resistant photoaffinity GTP analogue [32P]P3(4-azidoanilido)-P1-5'-GTP ([32P]AAGTP), was incubated with cerebral cortex membranes, AAGTP was transferred from tubulin to Gs alpha as well as Gi alpha. These results suggest that, in rat cerebral cortex membranes, the tubulin dimer participates in the stimulatory regulation of adenylyl cyclase by transferring guanine nucleotide to Gs alpha, as well as affecting the Gi-mediated inhibitory pathway. PMID- 7861168 TI - Enhanced glial fibrillary acidic protein RNA response to fornix transection in aged mice. AB - The effects of age on basal and lesion-induced changes in astrocyte RNA messages reported to respond to neurodegeneration were examined in the mouse brain. The first study found an age-related increase in glial fibrillary acidic protein RNA throughout the brain. Other astrocyte RNAs remained generally stable with age. We hypothesize this increase is due to astrocytes undergoing a mild reaction to the small amount of synaptic degeneration occurring with usual aging. To test this theory, we used an experimental model of modest synaptic loss in the hippocampus by transecting the fimbria/fornix bundle in mice and examined the same series of messages. In situ hybridization revealed the expected increase in glial fibrillary acidic protein RNA after the lesion; however, we unexpectedly found that aged mice showed a greater magnitude of this response, which appeared to develop more slowly. There was no significant change in the hippocampus for any of the other messages, although responses were observed at the site of transection. This study supports the idea that the age-related increase in glial fibrillary acidic protein may be secondary to modest synaptic degeneration. We also demonstrated an exaggerated reactive astrocytic response in aged mice, which may be associated with age-related deficits in reactive synaptogenesis and behavioral recovery in normal aging. PMID- 7861169 TI - Persistent translocation and inhibition of Ca2+/calmodulin-dependent protein kinase II in the crude synaptosomal fraction of the vulnerable hippocampus following hypoglycemia. AB - Alterations in the levels and activity of Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II) were studied in the rat hippocampus during and after insulin-induced hypoglycemic coma. A permanent loss of CaM-kinase II immunohistostaining in the neuronal layer begins at 10 min of isoelectricity in the tip of the dentate gyrus and at 30-min isoelectricity in the CA1 region. The reduction in immunohistostaining in the neurites is less pronounced. Immunoreactivity of CaM-kinase II on western blots increases in the crude synaptosomal fractions and decreases in cytosolic fraction, indicative of a translocation of CaM-kinase II. The translocation persists for at least 1 day of recovery after 30 min of isoelectricity in the vulnerable hippocampus (dorsomedial hippocampus) but not in the resistant hippocampus (dorsolateral hippocampus). Calmodulin binding to western blots shows changes similar to the immunoblots. Ca2+/calmodulin-dependent activity of CaM-kinase II in the crude synaptosomal fraction is elevated immediately before isoelectricity and is then inhibited during and after 30 min of isoelectricity, despite the increase of CaM kinase II immunoreactivity. This was seen in the vulnerable hippocampus. The data indicate that stimulus of translocation and inhibition of CaM-kinase II persist during the recovery phase, preceding neuronal degeneration in the vulnerable hippocampus. This may be of significance for hypoglycemia-induced neuronal death. PMID- 7861170 TI - Tyrosine hydroxylase phosphorylation in bovine adrenal chromaffin cells: the role of intracellular Ca2+ in the histamine H1 receptor-stimulated phosphorylation of Ser8, Ser19, Ser31, and Ser40. AB - Tyrosine hydroxylase (TOH), the rate-limiting enzyme in catecholamine biosynthesis, is regulated by phosphorylation. Activation of histaminergic H1 receptors on cultured bovine adrenal chromaffin cells stimulated a rapid increase in TOH phosphorylation (within 5 s) that was sustained for at least 5 min. The initial increase in TOH phosphorylation (up to 1 min) was essentially unchanged by the removal of extracellular Ca2+. In contrast, the H1-mediated response was abolished by preloading the cells with BAPTA acetoxymethyl ester (50 microM) and significantly reduced by prior exposure to caffeine (10 mM for 10 min) to deplete intracellular Ca2+. Tryptic-phosphopeptide analysis by HPLC revealed that the H1 response in the presence or absence of extracellular Ca2+ resulted in a major increase in the phosphorylation of Ser19 with smaller increases in that of Ser40 and Ser31. In contrast, although a brief stimulation with nicotine (30 microM for 60 s) also resulted in a major increase in Ser19 phosphorylation, this response was abolished in the absence of extracellular Ca2+. These data indicate that the mobilization of intracellular Ca2+ plays a crucial role in supporting H1-mediated TOH phosphorylation and may thus have a potentially important role in regulating catecholamine synthesis. PMID- 7861171 TI - Effect of ethanol treatment on rate and equilibrium constants for [3H] muscimol binding to rat brain membranes: alteration of two affinity states of the GABAA receptor. AB - Equilibrium binding curves were biphasic in control and ethanol-treated rats. [3H]Muscimol binds to sites of high (KDA of approximately 10 nM) and low (KDB of approximately 0.3-0.4 microM) affinity. Chronic ethanol treatment produced a decrease in BmaxA value, and the hyperbolic binding profiles were progressively affected by the chronic and in vitro ethanol treatments, with most of this effect corresponding to the high-affinity site. IC50 and Ki values were calculated for several competing ligands, using membranes from both control and ethanol-treated animals. The association and dissociation curves were also biphasic, using a radioligand concentration precluding a significant occupancy of the low-affinity sites, which suggests the existence of two forms or affinity states of the monoliganded receptor. Chronic ethanol treatment did not produce changes in the values of the dissociation rate constants (fast and slow phases). By contrast, we report for the first time a decrease in the values of the association rate constants, with this decrease being higher for the slow phase. Consequently, the dissociation equilibrium constants are two times higher in chronically ethanol treated animals for both phases. PMID- 7861172 TI - Hydroxyl radical-mediated oxidation of serotonin: potential insights into the neurotoxicity of methamphetamine. AB - When incubated with a hydroxyl radical (HO.)-generating system (ascorbic acid/Fe(2+)-EDTA/O2/H2O2), 5-hydroxytryptamine (5-HT; serotonin) is rapidly oxidized initially to a mixture of 2,5-, 4,5-, and 5,6-dihydroxytryptamine (DHT). The major reaction product is 2,5-DHT, which at physiological pH exists as its keto tautomer, 5-hydroxy-3-ethylamino-2-oxindole (5-HEO). Rapid autoxidation of 4,5-DHT gives tryptamine-4,5-dione (T-4,5-D), which reacts with the C(3)-centered carbanion of 5-HEO to give 3,3'-bis(2-aminoethyl)-5-hydroxy-[3,7'-bi-1H-indole] 2,4',5'- 3H-trione (7). The latter slowly cyclizes to 3'-(2-aminoethyl) 1',6',7',8'-tetrahydro-5-hydroxy-spiro[3H-indole-3,9'- [9H]pyrrolo[2,3 f]quinoline]-2,4',5' (1H)-trione (9). A minor amount of T-4,5-D dimerizes to give 7,7'-bi-(5-hydroxytryptamine-4-one) (7,7'-D). In the presence of GSH, the reaction of T-4,5-D with 5-HEO is diverted and, in the presence of sufficient concentrations of this tripeptide, completely blocked. This is because GSH preferentially reacts with T-4,5-D to give 7-S-glutathionyltryptamine-4,5-dione (11). The results of this investigation suggest that 5,6-DHT, 5-HEO, 7, and 9 are products unique to the HO.-mediated oxidation of 5-HT. Thus, the observation of other investigators that 5,6-DHT is formed in the brains of rats following a large dose of methamphetamine (MA) suggests that this drug might evoke HO. formation. However, the present in vitro study indicates that 5,6-DHT is a rather minor, unstable product of the HO.-mediated oxidation of 5-HT and suggests that detection of 5-HEO, 7/9, and 11 in rat brain following MA administration could provide additional support for HO. formation. Furthermore, one or more of the intermediates and major products of oxidation of 5-HT by HO. might, in addition to 5,6-DHT, contribute to the MA-induced degeneration of serotonergic neurons. PMID- 7861173 TI - Ultrastructure of the 5-hydroxytryptamine3 receptor. AB - We have determined the ultrastructure of 5-hydroxytryptamine3 (5-HT3) serotonin receptors purified from NG108-15 mouse neuroblastoma x rat glioma cells by electron microscopic examination of receptor particles embedded in uranyl acetate stain and metal replicas of rapidly frozen receptors. The 5-HT3 receptor can be modelled as a cylinder 11 nm in length and 8 nm in diameter with a closed end and a central cavity 3 nm in diameter. Analysis of the rotational symmetry of single receptor particles indicates that the 5-HT3 receptor is composed of five subunits arranged symmetrically around a central cavity. Together with evidence obtained for related proteins in other studies using ultrastructural, biochemical, or electrophysiological methods, our observations suggest that all members of the ligand-gated ion channel superfamily may possess a pentameric quaternary structure. PMID- 7861174 TI - Effects of arachidonic acid on dopamine synthesis, spontaneous release, and uptake in striatal synaptosomes from the rat. AB - Arachidonic acid (AA) markedly stimulated, in a dose-dependent manner, the spontaneous release of [3H]dopamine ([3H]DA) continuously synthesized from [3H]tyrosine in purified synaptosomes from the rat striatum. As estimated by simultaneous measurement of the rate of [3H]H2O formation (an index of [3H]tyrosine conversion into [3H]DOPA), the AA response was associated with a progressive and dose-dependent reduction of [3H]DA synthesis. In contrast to AA, arachidonic acid, oleic acid, and the methyl ester of AA (all at 10(-4) M) did not modify [3H]DA release. The AA (3 x 10(-5) M)-evoked release of [3H]DA was not affected by inhibiting AA metabolism, with either 5,8,11,14-eicosatetraynoic acid or metyrapone, suggesting that AA acts directly and not through one of its metabolites. AA also inhibited in a dose-dependent manner [3H]DA uptake into synaptosomes, with a complete blockade observed at 10(-4) M. However, AA (10(-4) M) still stimulated [3H]DA spontaneous release in the presence of either nomifensine or other DA uptake inhibitors, indicating that AA both inhibits DA reuptake and facilitates its release process. Finally, the AA (10(-4) M)-evoked release of [3H]DA was not affected by protein kinase A inhibitors (H-89 or Rp-8 Br-cAMPS) but was markedly reduced in the presence of protein kinase C inhibitors (Ro 31-7549 or chelerythrine). PMID- 7861175 TI - Dopamine D4-like receptor elevation in schizophrenia: cloned D2 and D4 receptors cannot be discriminated by raclopride competition against [3H]nemonapride. AB - Three independent studies have found that the density of dopamine D4-like receptors is elevated in postmortem brain striata in schizophrenia. This elevation has been questioned by a fourth study that used a different method and failed to detect a biphasic component when raclopride was used to complete against the binding of 1 nM [3H]nemonapride to schizophrenia tissue. To test whether this competition method could distinguish between dopamine D2 and D4 receptors, the present study used mixtures of only these two cloned receptors, free of all other receptors. Using combinations of cloned dopamine D2 and D4 receptors, this competition method could not resolve these components up to a level of 48% D4 receptors. Thus, the objections raised by the findings of the fourth study, mentioned above, do not appear valid. Furthermore, the present results indicate that the data using such a competition method actually mask a manyfold marked elevation in the density of dopamine D4-like receptors in schizophrenia. PMID- 7861176 TI - Dopamine transporter cysteine mutants: second extracellular loop cysteines are required for transporter expression. AB - Studies with thiol-modifying reagents have suggested that cysteines might play important roles in the function of the dopamine transporter (DAT). To identify DAT cysteines with important thiol groups, we have studied six mutant dopamine transporters in which cysteines were replaced by alanines. Substitutions of cysteines assigned to the DAT's second putative extracellular loop--positions 180 and 189--dramatically decreased the expression of the mutant transporters. Substitutions at positions 90, 242, 305, and 345 had no significant effect in decreasing dopamine uptake, MPP+ uptake, or cocaine analogue binding. Immunostaining COS cells transfected with Cys180 and Cys189 to Ala mutants revealed reduced membrane staining and prominent staining in perinuclear regions consistent with Golgi apparatus. These results suggest that cysteines i the DAT second extracellular loop may provide sulfide residues crucial to full transporter expression, at least in part, through interference with membrane insertion. Conceivably, they might also provide the targets for the influences of thiol-modifying reagents in modifying the function of the wild-type DAT expressed in striatal membranes. PMID- 7861177 TI - Inositol 1, 4, 5-trisphosphate receptor-mediated Ca2+ signaling in the brain. PMID- 7861178 TI - IgH intronic enhancer element HE2 (mu B) functions as a cis-activator in choroid plexus cells at the cellular level as well as in transgenic mice. AB - Immunoglobulin heavy-chain (IgH) gene expression is regulated largely by the IgH gene intronic enhancer (ENHiH), which is composed of multiple protein-binding motifs. These motifs are DNA elements that are important for the regulation of IgH gene transcription. It has been reported that the HE2 (mu B) and mu A motifs within the ENHiH affect B cell-specific gene expression. To examine the function of the HE2 and mu A elements in vivo, we established transgenic mouse lines. A deletion mutant of the human ENHiH that contains the HE2 and mu A motifs, but lacks the motifs corresponding to murine E5, E3, and octamer, functioned not only in B lymphocytes but also in choroid plexus cells, which secrete CSF. As a result, we obtained choroid plexus tumor-bearing transgenic mice and could establish choroid plexus carcinoma cell lines. In addition, using the luciferase assay, we confirmed at the cellular level that the HE2 motif shows a fair degree of enhancer activity in cultured choroid plexus carcinoma cells. These results suggest the existence of a trans-acting factor for the HE2 motif in choroid plexus cells. Actually, in this cultured cell line, the existence of a protein binding to the HE2 motif was demonstrated by a gel retardation assay. Due to the sequence homology between the HE2 motif and the Ets-binding sites, an Ets-related protein is a highly probable candidate for being the binding factor. PMID- 7861179 TI - Cloning and expression of a betaine/GABA transporter from human brain. AB - A cDNA clone encoding a human gamma-aminobutyric acid (GABA) transporter has been isolated from a brain cDNA library, and its functional properties have been examined in mammalian cells. The nucleotide sequence predicts a transporter with 614 amino acids and 12 putative transmembrane domains. The highest degree of amino acid identity is with a betaine/GABA transporter originally cloned from the dog termed BGT-1 (91%) and a related transporter from mouse brain (87%). These identities are similar to those for species homologues of other neurotransmitter transporters and suggest that the new clone represents the human homologue of BGT 1. The transporter displays high affinity for GABA (IC50 of 30 microM) and is also sensitive to phloretin, L-2,4-diaminobutyric acid, and hypotaurine (IC50 values of approximately 150-400 microM). The osmolyte betaine is approximately 25 fold weaker than GABA, displaying an IC50 of approximately 1 mM. The relative potencies of these inhibitors at human BGT-1 differ from those of mouse and dog BGT-1. Northern blot analysis reveals that BGT-1 mRNA is widely distributed throughout the human brain. The cloning of the human homologue of BGT-1 will further our understanding of the roles of GABA and betaine in neural function. PMID- 7861180 TI - Expression of the choline acetyltransferase gene depends on protein kinase A activity. AB - Choline acetyltransferase activity is barely detectable in a mutant pheochromocytoma PC12 cell line, A123.7, which is deficient in protein kinase A activity. Northern blot and polymerase chain reaction analyses showed that this mutant cell line has dramatically reduced levels of choline acetyltransferase mRNA, which correlates with the low level of enzyme activity. Transient transfection analysis was used to assess the functionality, in these cells, of an enhancer element and a cholinergic-specific repressor element derived from the human choline acetyltransferase gene. The results show that the enhancer element is inactive in the protein kinase A-deficient cell line. Cotransfection experiments with plasmids expressing the catalytic subunit of protein kinase A support this conclusion. These data indicate that protein kinase A regulates expression of the choline acetyltransferase gene at the transcriptional level by controlling the activity of an enhancer element. PMID- 7861181 TI - Coculture of astroglial and vascular endothelial cells as apposing layers enhances the transcellular transport of hypoxanthine. AB - In brain, astrocytes and endothelial cells are a major site of adenosine degradation. These two cell types, found in close apposition, constitute the wall of the brain's capillaries and serve as a site of hypoxanthine production and degradation. Both cell types possess the hypoxanthine salvage pathway and can incorporate hypoxanthine into nucleotides. This suggests that the endothelial astrocyte anatomical complex might play an important role in the brain's purine homeostasis. To test this hypothesis, cocultures of monolayers of vascular endothelial cells and astrocytes were grown over a porous membrane, in close apposition to one another, and studies on hypoxanthine transport and metabolism to uric acid were performed. The flux of hypoxanthine across the cell layers was simultaneously determined and compared with the flux of sucrose, as a probe of passive diffusion. Our results show that in endothelial, glial, and endothelial glial cell layers the hypoxanthine flux was greater than that of sucrose, and that the flux of hypoxanthine, but not of sucrose, was inhibited by adenine or by lowering the temperature. These results suggest that hypoxanthine moves across endothelial, glial, and endothelial-glial cell layers by a transport process. Furthermore, we found that hypoxanthine transport is enhanced when glial and endothelial cells are cocultured compared with that in glial or endothelial monolayers. In addition the coculture also resulted in a depression of xanthine oxidase activity. PMID- 7861182 TI - The proximo-distal spread of axonal degeneration in the dorsal columns of the rat. AB - The pivotal event in Wallerian degeneration is the breakdown of the axon. Establishing the pathophysiology of axonal degeneration has implications for the understanding of the pathogenesis of other types of nerve degenerations. A key aspect of the pathophysiology is the spatiotemporal pattern of spread after transection, an issue that has remained controversial. We have studied the progression of axonal degeneration in the dorsal columns of the rat following L4L5L6 dorsal radiculotomy. Axonal degeneration proceeds in a proximo-distal fashion, beginning near the site of transection and spreading up the dorsal columns at a net rate of about 3 mm h-1. In addition, there was early degeneration of the preterminal axons in the gracile nuclei. This pattern suggests that the 'clearing' of axonally transported materials from the distal stump by continued anterograde transport may underlie axonal breakdown after transection. PMID- 7861183 TI - Characterization of Schwann cells from normal nerves and from neurofibromas in the bicolour damselfish. AB - Schwann cells are an important component of neurofibromas, one of the primary lesions encountered in neurofibromatosis type 1 in man. A central question in studies of neurofibromatosis type 1 has been whether the Schwann cells present in these tumours are intrinsically abnormal or exhibit abnormal phenotypes in response to stimuli from other cell types in these tumours. Damselfish neurofibromatosis is a naturally occurring disease in a species of marine fish, the bicolour damselfish, that is being developed as an animal model of neurofibromatosis type 1. Affected fish exhibit multiple neurofibromas and neurofibrosarcomas (malignant schwannomas). The present study compares the morphology, antigen expression and proliferative capacity in vitro of Schwann cells derived from peripheral nerves of normal, healthy fish with cells isolated from both spontaneously occurring and experimentally induced neurofibromas. Schwann cells from normal nerves expressed S100 antigens but not fibronectin or glial fibrillary acidic protein antigens and were similar in morphology and proliferative capacity to Schwann cells isolated from mammalian peripheral nerves. Tumour-derived cultures contained variable proportions (27-79%) of S100 positive cells that were identified as Schwann cells based on this feature. These tumour-derived Schwann cells exhibited a different morphology than normal Schwann cells, usually exhibited an increased reactivity to anti-S100 antibodies and were able to proliferate in vitro without added mitogens. Repeated subculturing of tumour-derived cultures led to the production of six cell lines all of which were composed exclusively of Schwann cells as indicated by S100 expression. These findings show that Schwann cells are an important component of tumours in Damselfish neurofibromatosis and that these cells are morphologically and physiologically altered in this disease. Observations of cell lines also suggest that tumour-derived Schwann cells are intrinsically abnormal and that this phenotype is not a result of stimuli from other cell types in the tumours. PMID- 7861184 TI - Inhibition of CNS myelin development in vivo by implantation of anti-GalC hybridoma cells. AB - Implantation of hybridoma cells that secrete a monoclonal antigalactocerebroside into the dorsal columns of < or = 9-day-old rat spinal cord results in failure of development of dorsal column myelin in the vicinity of the implant. Clusters of apparently undamaged amyelinated axons remain among the hybridoma cells. Ventral myelin is unaffected. These in vivo results support antibody-mediated inhibition of myelin formation as a potential mechanism underlying failure of remyelination in multiple sclerosis. PMID- 7861185 TI - Developmental expression of G-proteins and adenylyl cyclase in peripheral olfactory systems. Light microscopic and freeze-substitution electron microscopic immunocytochemistry. AB - Light microscopic immunohistochemistry coupled with freeze-substitution electron microscopic immunocytochemistry was used to localize alpha-subunits of G-proteins and type III adenylyl cyclase in developing rat olfactory epithelia. Some cilia immunoreacted with antibodies to GS alpha and type III adenylyl cyclase as early as prenatal day 15 (E15; E1 = sperm-positive), but immunolabelling with antibodies to Golf alpha was not observed until E16. From then on numbers of receptor cells with immunolabelled cilia increased for all three probes. Immunoreactivity for antibodies to the olfactory signal-transduction proteins tended to parallel cilium development, though Golf alpha lags somewhat behind. Newly formed cilia labelled along their lengths, whereas mature cilia labelled predominantly along their long distal parts. Dendritic knobs and ciliary necklaces showed little or no labelling. While at E22 most multiciliate cells immunolabelled with antibodies to Gs alpha, Golf alpha, and type III adenylyl cyclase, not all of these cells labelled with antibodies to olfactory marker protein. Olfactory axons immunoreacted more intensely than epithelial surface structures with antibodies to Gs alpha at E15; the reverse occurred by about E18. Immunoreactivity with antibodies to alpha-subunits of the G-proteins Go, Gq/G11, and Gi was also found as early as E15. Antibodies to Go alpha labelled receptor cell dendritic knobs and cilia during development only. Antibodies to Gi alpha labelled Bowman's glands, whereas those to Gq alpha/G11 alpha bound to receptor cell cilia and axons (primarily vomeronasal), and supporting cell microvilli. We propose that Gs is the predominant G protein in cilia of immature olfactory receptor cells, while Golf is predominant in cilia of mature cells. Axonal immunoreactivity for some G-protein antibodies suggests G-protein participation in processing of olfactory axon and/or axon terminal-bound signals. PMID- 7861186 TI - The folate receptor in central nervous system malignancies of childhood. AB - The folate receptor is a membrane linked glycoprotein that participates in the cellular accumulation of 5-methyltetrahydrofolic acid, methotrexate and 5,10 dideazatetrahydrofolic acid. Relative receptor overexpression has been observed in several malignant cell lines and tissues. In this study we determined receptor expression using western blot analysis in primary pediatric malignancies involving the central nervous system. This study suggests that ependymoma tumors have a high frequency of receptor expression which may reflect a specific cytogenetic abnormality or the cellular origin of these tumors. The potential role in developing selective chemotherapy mediated by the folate receptor is also discussed. PMID- 7861187 TI - Variation of the magnetic relaxation rate 1/T1 of water protons with magnetic field strength (NMRD profile) of untreated, non-calcified, human astrocytomas: correlation with histology and solids content. AB - The magnetic relaxation rate 1/T1 of tissue water protons was measured over a wide range of magnetic field strengths (NMRD profile) for 92 fresh surgical specimens of astrocytomas to search for correlations of 1/T1 with tumor histology, as determined by light microscopy, and to assess the diagnostic potential of NMRD profiles for grading astrocytomas. A third goal was to elucidate the molecular determinants of 1/T1. Each specimen was histologically graded and inspected for evidence of mineral deposits (Ca, Fe); its dry weight was determined and expressed in % of original wet weight. To minimize variability not directly related to tumor grade, this initial report is limited to NMRD profiles of 47 non-calcified, non-hemorrhagic, untreated astrocytomas. For these, the mean value of 1/T1 at very low magnetic field strengths was found to increase with increasing grade of malignancy; no clear correlation could be demonstrated at high fields where most imaging is done. The spread of 1/T1 for different grades of malignancy is large, however, and the overlap significant, even at the lowest field, so that astrocytomas can not be graded by NMRD profiles alone. Average 1/T1 and average dry weight increase with grade of malignancy; but the variability of 1/T1 among specimens of the same dry weight is large, indicating that at least one other cellular parameter, not variable in normal tissue, influences 1/T1 strongly. We hypothesize that this parameter reflects changes at the molecular level in size distribution, mobility, or intermolecular interaction of cytoplasmic proteins. Which specific changes are induced by malignant transformation in astrocytomas remains to be investigated. PMID- 7861188 TI - Levels of water-soluble antioxidants in astrocytoma and in adjacent tumor-free tissue. AB - The aim of the present study was to investigate the oxidative status in astrocytoma. Samples of brain tissue from the centre to the periphery of the tumor were obtained from 11 astrocytoma patients undergoing computer tomography guided stereotaxic operation, who had been previously treated with the corticosteroid dexamethasone. Part of the sample was investigated histologically for clarification of tumor type, and the presence of neoplastic and non neoplastic tissue and necrosis. The rest was used for the quantification of the antioxidants ascorbic acid, uric acid, glutathione and cysteine by high performance liquid chromatography, and for quantification of DNA. Levels of antioxidants were calculated as micrograms/g fresh tissue and mumol/g DNA, a parameter related to cell content. There was significantly more DNA in neoplastic samples than in non-neoplastic ones, indicating increased cell density. Uric acid (micrograms/g fresh tissue) was significantly increased in neoplastic compared with non-neoplastic tissue, and levels were even higher in necrotic tissue. There were no significant differences between neoplastic and non-neoplastic tissue levels of ascorbic acid, glutathione or cysteine, expressed as micrograms/g fresh tissue. However, when levels of these three compounds were expressed as mumol/g DNA, i.e. taking into account the higher cell density, ascorbic acid, glutathione and cysteine were significantly reduced in neoplastic samples compared with non neoplastic ones. Results thus show that there are differences between the antioxidant levels in astrocytoma and non-neoplastic tissue, providing additional support for the hypothesis that free radicals play a role in tumor growth. PMID- 7861189 TI - O6-alkylguanine-DNA alkyltransferase activity of human malignant glioma and its clinical implications. AB - Activity of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) is an important determinant of responsiveness of tumor cells to chloroethylnitrosoureas (CENUs), representative chemotherapeutic agents for primary malignant gliomas. In order to assess the real states of this repair protein in human malignant gliomas, we assayed AGT activity in surgically extirpated 42 malignant glioma samples and studied the distribution of the activity under certain clinical conditions. There were wide variations in AGT activity between individuals. No significant difference in AGT activity on average was seen either between glioblastoma and anaplastic astrocytoma, nor between primary and recurrent tumors. Among 42 malignant gliomas, 7 samples (16.7%) had low AGT activity less than 0.1 pmoles/mg protein. In the case of glioblastoma, tumors possessing higher AGT activity tended to be less responsive to post-operation remission-induction therapy including CENUs. The result of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) chemosensitivity assay by using the corresponding surgical specimens suggested a close relationship between cellular resistance to CENUs and AGT activity. It was found to be unlikely that a short term administration of CENUs had a significant effect on AGT activity of brain tumors in human body. We could detect a bit of definite evidences of the relevance of AGT to resistance to CENUs and need to conduct further investigations for other resistance factors. PMID- 7861190 TI - Inhibition of collagenolytic activity relates to quantitative reduction of invasion in vitro in a c-Ha-ras transfected glial cell line. AB - The function of proteases in brain tumor invasion is currently not well established. For tumors of epithelial and fibromatous origin collagenase production can enhance the invasive capacity of cells to penetrate basement membranes. We showed previously that a c-Ha-ras transformed glial cell line (CxT24neo3) invaded hamster brain tissue in vivo. These cells were also capable of invading reconstituted basement membrane and embryonic chick hearts in vitro. Since the histopathology of CxT24neo3 tumors mimics that of glioblastoma multiforme in humans, CxT24neo3 was used as the model in vitro for this type of brain tumor. Presently, we detected by zymogram analysis a gelatinase that was secreted by CxT24neo3 and that had an apparent molecular mass of 62 kD. To verify whether gelatinase affected invasion in vitro of these glial cells we determined the efficacy of a substrate specific collagenase inhibitor on invasion in vitro. GM6001 is a synthetic polypeptide that specifically occupies the substrate binding sites of metalloprotease. Since this drug did not show cytotoxicity, its specificity for metalloprotease is a valuable tool to evaluate the physiological function of these enzymes on invasion. We found that treatment of CxT24neo3 with GM6001 reduced the fraction of invading CxT24neo3 cells through reconstituted basement membrane. These data suggest that metalloproteases can stimulate brain tumor invasion. PMID- 7861191 TI - Clonal analysis of human astrocytomas. AB - Clonal analysis of many human cancers have generally confirmed that they are monoclonal. Although astrocytic neoplasms are the most frequently occurring primary tumors in the central nervous system, their clonal composition has not been systematically studied. In this report, the clonal composition of 22 human astrocytomas of all histological grades (2 well-differentiated astrocytomas, 3 anaplastic astrocytomas and 17 glioblastoma multiforme) was determined by analysis of the pattern of X-chromosome inactivation. Leukocyte and non-tumor brain DNA were used as controls. In addition, specimens from different parts of four glioblastoma multiforme were analyzed to determine whether remote areas of the same tumor had the same clonal composition. Eighteen of nineteen informative astrocytomas had a monoclonal pattern of X-chromosome inactivation; one glioblastoma multiforme had loss of heterozygosity on the X chromosome. Specimens from different areas of the same tumor all had identical patterns of X-chromosome inactivation. Leukocytes and non-tumor brain used as controls uniformly had a polyclonal pattern of X-chromosome inactivation. Furthermore, loss of heterozygosity for chromosomes 10 or 17 p loci was found in 64% (9/14) of informative specimens and identical allelic patterns were observed in specimens from different areas of the same tumor. Our results demonstrate that human astrocytomas from low to high-grade are characterized by monoclonal cell populations. The presence of monoclonality in even low-grade neoplasms suggests that in astrocytic tumors the establishment of monoclonality occurs quite early. Also, the finding of a monoclonal pattern in intermediate- and high-grade astrocytomas further supports the hypothesis that clonal expansion underlies astrocytic tumor progression. PMID- 7861192 TI - Paraneoplastic sensorimotor neuropathy associated with breast cancer. AB - Paraneoplastic sensorimotor neuropathy occurs in association with many different types of cancer. The clinical findings are heterogeneous, and the pathogenesis is unknown. We have encountered 9 women with breast cancer and shared neurological features that suggest a distinct paraneoplastic syndrome. The syndrome is characterized by upper and lower extremity paresthesias and numbness, itching, muscle weakness and cramps, and in some, radicular symptoms and signs. Serum and CSF inflammatory changes suggested an immune pathogenesis but none had detectable antibodies directed at nervous system elements. Six patients presented with neuropathy 2 months to 8 years before the discovery of the breast cancer. In 7 the neoplastic disease was localized to the breast and axillary lymph nodes. The neurologic course was chronic in all, and while symptoms were annoying, disability was minimal until late. One improved transiently with plasmapheresis, and three had mild transient improvement with treatment of the cancer. Recognition of this paraneoplastic syndrome may forewarn the physician of an underlying breast malignancy. PMID- 7861193 TI - Radiotherapy response of cerebral metastases quantified by serial MR imaging. AB - A patient with cerebral metastases, treated with radiotherapy, underwent serial gadolinium-enhanced MR imaging. The MR images were quantified using home developed software to evaluate the changes in volumes of tumor mass and edema after radiotherapy (mean precision of the quantification technique less than 5%). The decrease in tumor volume and edema observed after radiotherapy preceded clinical improvement. The presented technique can be used to accurately assess, more directly than using clinical scales, the effect of putative therapies. PMID- 7861194 TI - Influence of extent of surgery and tumor location on treatment outcome of patients with glioblastoma multiforme treated with combined modality approach. AB - Between 1988 and 1991, eighty-six patients with glioblastoma multiforme were evaluated in order to define the influence of extent of surgery and tumor location on treatment outcome. Patients underwent surgery followed by postoperative hyperfractionated radiotherapy and chemotherapy delivered according to one of two consecutive protocols. Surgery consisted of biopsy in 25 (29%) patients and subtotal or gross total tumor resection in 61 (71%) patients. Frontally located tumors were noted in 26 (30%) patients and other tumor locations were noted in 60 (70%) patients. Patients having more radical surgery had longer median survival time (MST) and higher 1- and 2-year survival rates than those with biopsy only (56 vs 29 weeks, respectively; 62% and 23% vs 16% and 0%, respectively; p = 0.00000). Patients having frontally located tumors had longer MST and higher 1- and 2-year survival rates than those with other tumor locations (101 vs 47 weeks, respectively; 76% and 44% vs 37% and 2.5%, respectively; p = 0.00001). Multivariate analysis confirmed that extent of surgery and tumor location were independent prognostic factors in patients with glioblastoma multiforme. Regarding progression-free survival, patients having more radical surgery had longer median time to tumor progression (MTP) than those with biopsy only (33 weeks vs 21 weeks, respectively). Also, progression-free survival at 1 year was higher in radically resected group than in biopsy only group (20% vs 0%, respectively; p = 0.00000). Patients with frontally located tumors had longer MTP (42 weeks) and higher progression-free survival at 1 year (42%) than those with other tumor location (28 weeks and 1.7%, respectively; p = 0.00002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861195 TI - A review of the microbiology of amoxycillin/clavulanic acid over the 15 year period 1978-1993. AB - A review of the published literature over the period 1978-1993 was undertaken to assess any changes in the prevalence of beta-lactamase-producing bacterial pathogens and also any changes in the susceptibility in these pathogens to amoxycillin/clavulanate. The review has involved the examination of over 1500 publications. The review shows that in general there has been an increase in the frequency of beta-lactamase-producing pathogens resistant to ampicillin and amoxycillin but there is no evidence for any significant increase in resistance to amoxycillin/clavulanate over the period of the review. PMID- 7861196 TI - Incidence of lower respiratory tract infections caused by Mycoplasma, Chlamydia and Legionella: an Italian Multicenter Survey. AB - A collaborative retrospective study based on serologic diagnosis was conducted to assess the etiological role sustained by privileged pathogens in Italy. The results obtained indicate the Mycoplasma, Chlamydia and Legionella are important etiologic agents of lower respiratory tract infections in Italy since they account for about 31% of the cases taken into consideration in this survey. We found a high incidence of M. pneumoniae (12.3%), C. pneumoniae (10.5%) and L. pneumophila (8.3%). These results are in line with similar figures reported in the recent literature. While the data gathered in our survey do not allow us to clarify the nature of the agents involved in the etiology of the majority (70%) of the respiratory infections occurring in Italy, it seems safe to assume that after Streptococcus pneumoniae and Haemophilus influenzae, the privileged pathogens represent the most common cause of lower respiratory tract infections. PMID- 7861197 TI - Therapeutic efficacy and tolerability of brodimoprim in comparison with doxycycline in acute sinusitis in adults. AB - OBJECTIVE: To compare efficacy and tolerability of brodimoprim tablets with doxycycline tablets in adults with acute sinusitis. DESIGN: Open, randomized, controlled phase III study, with parallel groups. PATIENTS: Of the 70 enrolled patients, 56 adults of both sexes with a mean age of 33 years were evaluable. STUDY DRUGS: One brodimoprim 200mg tablet or one doxycycline 100mg tablet was administered once daily for 8 to 12 days (on the first treatment day all patients received the loading dose consisting of 2 tablets of the corresponding compound). CLINICAL OUTCOME: In the brodimoprim group 96.4% of the patients were judged cured/improved; in the doxycycline group 96.2%. BACTERIOLOGICAL OUTCOME: Eradication of the causative pathogen/s was achieved in 87.5% of the patients treated with brodimoprim and in 60% of the doxycycline group. SAFETY OUTCOME: Tolerability was judged as very good/good in 89.7% of the patients treated with brodimoprim and in all patients receiving doxycycline. Gastrointestinal skin, CNS and various other reactions were reported by 13 patients; 3 of them had to discontinue treatment. Discontinuation of therapy: 8 more patients withdrew from the study due to inactivity of the compound or reasons unrelated to the drugs. CONCLUSION: Brodimoprim was shown to be effective in the treatment of acute sinusitis in adults, its efficacy being equal to that of doxycycline. The assessments showed a positive clinical response to the medication in 96.4% of the patients treated with brodimoprim and 96.2% of the patients taking doxycycline. Both compounds were well tolerated and all side effects were of mild nature and reversible. PMID- 7861198 TI - Synergism between gamma interferon and doxorubicin in a human MDR colon adenocarcinoma cell line. AB - Recent interest in cancer therapy derives from the ability of interferons to synergistically increase the activity of chemotherapeutic agents. To understand the biological basis of this synergism we evaluated the effects of human recombinant IFN-gamma on the expression of the mdr1 gene and on the cellular growth of a human colon adenocarcinoma cell line (LoVo) and its MDR subline (LoVo/Dx) after coincubation with doxorubicin. Treatment with IFN-gamma showed unchanged levels of MDR1-glycoprotein, no perturbation on cell cycle distribution and a significant reduction of colony formation in both lines (P < 0.05) starting from 100 U/ml. A synergistic effect was observed in the LoVo/Dx cell line when doxorubicin was added after exposure to 0.1-10 U/ml of IFN-gamma. Our data indicate that the effects of IFN-gamma, independent from action on cell proliferation and from modulation of p-glycoprotein expression, are a cause of the synergistic activity between this lymphokine and conventional chemotherapeutic agents such as doxorubicin. PMID- 7861199 TI - Effect of buthionine sulfoximine on the sensitivity to doxorubicin of parent and MDR tumor cell lines. AB - We have studied the interaction of glutathione-depleting concentrations of buthionine sulfoximine (BSO) with the anti-proliferative activity of doxorubicin (DXR) in three tumor lines, the mouse B16 melanoma. Friend erythroleukemia and the human K562 leukemia, both as DXR-sensitive and-resistant (with typical multidrug resistance) variants. BSO significantly enhanced the DXR effects in the wild-type Friend and K562 leukemias, and especially in the drug-resistant subline of Friend leukemia. BSO did not modify DXR accumulation and retention in the latter clone. Moreover, neither BSO nor verapamil used alone completely reversed the resistance to DXR of this cell line; their combination was more efficient and increased its drug sensitivity to a level closer to that of the parental counterpart. These results seem to indicate that the status of glutathione and of the enzymes related to it contributes to the resistance of Friend leukemia to DXR. An interesting additional finding was that BSO significantly synergizes with the antiproliferative effects of vincristine in the drug-sensitive variants of Friend and K562 leukemias. PMID- 7861200 TI - Combined chemo-immuno-hormonotherapy of advanced renal cell carcinoma. AB - Thirty-five patients (pts.) with advanced renal cell carcinoma were treated with a combination of vinblastine (5 mg/m2/IV) plus epirubicin (50 mg/m2/IV) every 3-4 weeks, alpha-2-A-interferon (9 x 10(6) U/IM 3 times in the 1st week, then 18 x 10(6) U/IM 3 times weekly), and medroxyprogesterone acetate (2,000 mg/os/day plus 500 mg IM/week). Thirty-one patients were males and 4 were females with a median age of 63 years (range 35-75) and median performance status of 70% (range 50 90%). We observed nine partial remissions (26%) with median duration of 40 weeks (range 20-232+). Fifteen pts. had no change (43%) while 11 pts. progressed (31%). The main side-effects were: leukopenia (29/35, 83%) with median nadir of 3,100 WBC/mm3 (range 510-3,990) and fever (32/35, 91%). Thrombocytopenia occurred in 4 pts. (11%), anemia in 5 (14%), asthenia in 12 (34%), nausea/vomiting in 12 (34%), alopecia in 8 (23%) and stomatitis in 3 (8.5%). Two patients stopped the therapy with medroxyprogesterone acetate because of muscular cramps. Median survival was 65 weeks (range 6-327+). We conclude that the combination of recombinant alpha 2A interferon-vinblastine-epirubicin and medroxyprogesterone acetate has modest but definitive activity in patients with advanced renal cell carcinoma. PMID- 7861201 TI - Restoration of polymorphonuclear leukocyte function in elderly subjects by thymomodulin. AB - Senescence is a specific physiological evolution of human beings associated with a reduction in the functionality of several apparatuses, including the immune system. Thymomodulin (TMD) contains thymus polypeptides (< 10,000 D) and it has been used in a variety of disorders associated with defective immunological functions. The aim of this study was to investigate the effect on polymorphonuclear leukocyte (PMNs) phagocytosis and oxidative burst of a 6-week treatment with 160 mg/day TMD orally in elderly subjects (85.5 +/- 9.7 years). Elderly subjects have impaired PMN phagocytosis and the following release of oxidant radicals. Treatment with TMD for 6 weeks had a restoring effect; phagocytosis and the phagocytic index were significantly improved, with increases of 132.6% and 112.5%. These findings indicate that TMD might be given to enhance the immunodefenses of immunocompromised elderly subjects. Luminol-dependent chemiluminescence was increased by 15.6%, which was not significant, indicating a different response between phagocytosis and release of oxidant radicals. PMID- 7861202 TI - [Experimental evaluation of antibiotics as immunomodulators]. AB - Since the pioneer work by Metchnikoff, the goal of cooperation between therapeutics and the host defence system (HDS) has been sought after. This area of research received less attention after the introduction of antibiotics. Although, the predictive efficacy of antibacterial agents (ABA) is still evaluated in terms of MICs, MBCs, and pharmacokinetics, much evidence derived from clinical studies underlines the need for synergy between HDS and these drugs to obtain optimal therapeutic efficacy. The analysis of the immunomodifying properties of ABA has come under intense study. The majority of ABA does not substantially affect the functioning of the immune system at least in vivo, despite in-vitro observations of enhancement/inhibition of various immune parameters by some cephalosporins, macrolides, cyclins, aminoglycosides, etc. By contrast, chloramphenicol, sulphonamides and various beta-lactams may be responsible for drug-induced neutropenia whereas macrolides and quinolones, due to their high phagocytic uptake, synergize with phagocytes to destroy intracellular pathogens. Recently, the concept of Biological Response Modifier (BRM)-antibiotics has come under the limelight with the introduction of cefodizime, a new parenteral cephalosporin, which seems to be endowed with immunomodulating properties. This latter aspect has been demonstrated in vitro (potentiation of the phagocyte antimicrobial activity), ex vivo in immunocompromised animals and humans (restoration of various immune parameters) and in vivo (infection models using both sensitive and resistant species). Although the underlying mechanism has not been elucitated, the chemical structure responsible for this BRM activity has been recognized as the thio-thiazolyl moiety at C3 position of the cephem nucleus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861203 TI - [Immune response to antibiotics in patients with secondary immunodeficiencies]. AB - A biological response modifier (BRM) has been defined as an agent able to modulate effector mechanisms or mediators of host defence. Some antibiotic molecules have been shown to display a BRM like activity, being able to enhance immune responses (certain cephalosporins), to synergize with the immune effectors (macrolides, quinolones) or alternatively, to depress immune functions (tetracyclines or antimycotic drugs). The BRM-like activity of different antibiotic molecules has been widely reported in in vitro studies as well as ex vivo in experimental animal models. Only recently some Authors have approached the problem by investigating whether the in vivo administration of antibiotic was able to affect different immune effector functions, either in healthy subjects or in patients. The main question in the field is the possible clinical impact of the connections between antibiotics and the immune system, particularly in subjects with acquired immunodeficiency in whom the impairment of the immune responses leads to increased susceptibility to infectious processes. Ex vivo data seem to suggest that cefodizime, one of the newest third-generation cephalosporins, is able to enhance phagocyte and mononuclear cell functions in healthy volunteers, thus confirming the possibility of combining an antibacterial efficacy with the ability to restore or enhance immune responses. Comparable data in studies investigating the effect of cefodizime on immune functions in immunocompromised patients such as elderly subjects, hemodialyzed or diabetic patients, BPCO subjects, patients undergoing surgical stress and patients with multiple myeloma are more important from a practical clinical point of view.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861204 TI - [Microbiological aspects of antibiotics with immunomodulating action]. AB - Through the introduction of a 7-mercapto-1,3-thiazole chain at position 3' of the dihydrothiazine ring, cefodizime, which is structurally similar to cefotaxime, has acquired a number of remarkable immunomodulatory properties while retaining a potent antimicrobial spectrum of activity. Cefodizime penetrates in fact readily through the bacterial cell wall and interacts with its molecular targets in such a way that at high concentrations cell death and lysis are rapidly induced. Its spectrum of action encompasses the Enterobacteria, Neisseriae, Haemophilus, Moraxella catarrhalis, methicillin-susceptible staphylococci and streptococci, with pneumococci included. Cefodizime is devoid of useful potency against Pseudomonas, Acinetobacter and enterococci. Given the wide occurrence of strains synthesizing beta-lactamases in several primary pathogens of community-acquired and nosocomial infections, the complete stability of cefodizime towards the most prevalent of these hydrolytic enzymes (TEM-1, TEM-2, SHV-1, BRO-1 and the staphylococcal penicillinases) seems reassuring. Only a few chromosomally-coded and extended spectrum beta-lactamases produced by gram-negative microorganisms inactivate the new cephalosporin. Since the distribution of pathogens carrying these enzymes depends on the local trends of antibacterial consumption and cannot be easily predicted, a large multicenter study in Italy has recently assessed the antibacterial potency of cefodizime, in comparison with suitable drugs, on 1985 selected nosocomial strains. In this survey cefodizime was more effective in vitro than amoxicillin-clavulanate, gentamicin and piperacillin while being substantially similar in the rates of eradication of gram-negative and gram positive organisms to other third generation cephalosporins like ceftazidime and ceftriaxone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861205 TI - [Do effects of biological response modifiers in vitro correspond to clinical results?]. AB - There has been renewed interest in drug-host defence interaction because of increasing numbers of immunocompromised individuals in whom even a marginal influence on host response may have a beneficial effect on clinical outcome. The immunomodulating activity of several antibiotics has been investigated in the past. Unfortunately most of these studies have focussed on in vitro effects. Many controversies arise from the use of non-standardized techniques. In vivo experiments performed in animals might be far from the clinical situation. The effect of antibiotics on pagocyte function has been studied most intensively. Immunostimulating and depressing activities of antibiotics have been described. The clinical relevance is still controversial, e.g., the intracellular uptake of an antibiotic does not necessarily mean better microbial killing. Synergistic activities have been found with some macrolides and newer cephalosporins, but until now clinical studies in humans are still missing. Not only patients with abnormal host defence mechanisms, but also patients with transient immunosuppression during operations or after burns, could benefit from antibiotics with additional immunomodulating activities. More studies in humans are required before optimal clinical applications can be recommended. PMID- 7861206 TI - [Infections of the lower respiratory tract: clinical experimentation with a new cephalosporin]. PMID- 7861207 TI - [Interactions between antibiotics and immune defenses. Introduction]. PMID- 7861208 TI - [Interactions between antibiotics and immune defenses. Conclusions]. PMID- 7861209 TI - [Pathogenetic mechanisms responsible for producing a secondary immunodeficiency state]. AB - Abnormalities of the immune response can be secondary to old age, to several pathologic conditions (i.e. diabetes mellitus, renal failure, solid and lymphohematologic neoplasias, leukopenia, malnutrition, autoimmune diseases, AIDS), to surgical stress or to burns, and to immunosuppressive therapies, both medical (corticosteroids, cytotoxic agents, antilymphocytic globulins) and surgical (splenectomy) as well as radiant (extensive radiotherapy). Old age can affect both humoral (reduced antibody synthesis) and cell-mediated (thymus involution, diminished ratio Th/Ts, depression of both delayed hypersensitivity reactions and cytotoxic activity of K cells) immune response. Hyponutrition, often observed in the elderly, adds a reduced production of secretory IgA, lysozyme and interferon, diminished complementary activity, phagocytosis defects, and vitamin deficits. Furthermore, in some chronic diseases we can observe reduced primary antibody response or depression of delayed hypersensitivity reactions (renal failure, neoplasias), changes in leukocyte functions (diabetes mellitus, leukemias and lymphomas) and, in particular in solid neoplasias, increased activity of Ts lymphocytes and the presence of circulating immunocomplexes. Changes in phagocytosis, opsonization and chemotaxis are typically seen in burns, whereas surgical stress can cause some inhibition of cell-mediated immunity. Finally, after splenectomy it is possible to observe an increased synthesis of IgA and IgG and, on the contrary, reduced production of IgM and properdin. PMID- 7861210 TI - Treatment failure in otitis media: an analysis. AB - An epidemiological study was conducted in order to monitor the involvement of penicillin-resistant pneumococci (PRP) in treatment failure in acute otitis media (AOM), in an area of France where resistance to antibiotics is high. A total of 293 children presenting to 12 ear, nose and throat (ENT) specialists were included in the study. The mean age of the patients was 15.3 months and most of the children (58.7%) were attending day care centres. Bacteriological sampling demonstrated that in 146 cases (49.8%), no pathogen was present at the time of treatment failure. In the remaining patients Streptococcus pneumoniae was the most frequently recovered pathogen, being isolated from 81/147 (55.1%) of bacteriologically documented cases. Serotype 23F was the predominant strain, representing 53% of all S. pneumoniae isolates recovered. Resistance or reduced susceptibility to the prescribed antibiotic was seen in 70/81 (86.4%) of the S. pneumoniae isolates. In 32 out of 49 children administered a beta-lactam antibiotic, treatment failure involved PRP. Amoxycillin seemed to be the most active oral beta-lactam against these pathogens. The multiresistance of S. pneumoniae poses a serious therapeutic problem and should make myringotomy and bacteriological sampling obligatory in cases of antibiotic treatment failure. PMID- 7861211 TI - The continuing problem of 'hospital staphylococci': why? AB - Nosocomial infections due to staphylococci continue to pose a serious health concern worldwide. Methicillin-resistant Staphylococcus aureus (MRSA) is an important and growing cause of staphylococcal infection. The incidence of MRSA varies throughout the world, but is particularly high in Japan where the incidence is four-times that seen in Europe. The emergence of coagulase-negative staphylococci (CNS) has increased as a significant pathogen in infections associated with prosthetic implants. Evidence suggests that hand carriage by hospital staff is one way in which CNS are introduced onto catheters, intravenous lines and other implant devices. Control measures in the UK have concentrated on the reservoirs of infection, with the aim of preventing infection and the resulting morbidity, mortality and economic burden. At the North Middlesex Hospital, London, UK, an aggressive prophylactic policy for MRSA has been employed since 1987. Data show that it is six times cheaper to treat a carrier than it is to treat an infected patient. Prophylaxis therefore provides a more cost-effective way of controlling the spread of MRSA infection. Such stringent control strategies, coupled with increased awareness and adequate funding, are necessary if the spread of resistant bacteria is to be limited. PMID- 7861212 TI - Healthcare workers and the incidence of nosocomial infection: can treatment of one influence the other?--a brief review. AB - Nasal carriage by health care workers represents an important hospital reservoir of Staphylococcus aureus. Approximately 25% of all hospital-based healthcare workers are stable nasal carriers. Several studies in the US and UK have shown that following treatment of this group with a single 5-day course of intranasal mupirocin, nasal carriage was usually eradicated within 24 hours, and after 12 weeks was only present in 25% of participants. Long-term follow-up in one institution after 52 weeks showed that there were significantly fewer carriers in the mupirocin group than in the group receiving identical placebo. In the same study, between 30% and 50% of those hospital workers who carried S. aureus in their nose, before the start of therapy, were also hand carriers. After treatment, a dramatic reduction in hand carriage of S. aureus was noted, in contrast to no change in the placebo group. After 6 months, the level of hand carriage was still statistically lower in the mupirocin group than in those given placebo. The association between nasal carriage and hand carriage makes it important that health care workers decontaminate their hands effectively between patients. Current evidence suggests, however, that compliance with such control measures is low. Other studies examining the role of S. aureus nasal carriage in the development of post-operative wound infection, have shown that almost half of those isolates recovered from the wound site were present in the nose of the patient pre-operatively. Due to its ability to eliminate nasal carriage of S. aureus, current studies are investigating whether intranasal mupirocin can prevent post-operative wound infections in patients undergoing surgery. PMID- 7861213 TI - Antibiotic-resistant pneumococci--facts and fiction. AB - The effective treatment of infections caused by penicillin-resistant pneumococci is dependent upon the rapid and accurate laboratory assessment of bacterial susceptibility. The most reliable methods for the susceptibility testing of pneumococci are those of minimum inhibitory concentration (MIC) determination, disk diffusion and the more recently developed E-test. The E-test, in particular, has made pneumococcal testing much easier and allows results to be obtained more rapidly. Current breakpoint recommendations for the susceptibility of pneumococci to penicillin and cephalosporins have been criticised and continue to be the subject of debate. Evidence suggests that strains of pneumococci with an MIC value of 0.06 mg/L for penicillin should be classified as being of intermediate susceptibility. Many of these strains produce zone diameters less than the susceptible breakpoint in oxacillin/methicillin disk procedures. Other proposed changes to NCCLS guidelines are also discussed. Surveys of susceptibility patterns of pneumococci to antibiotics are important in assessing the value of agents in the management of infectious disease. Susceptibility studies have demonstrated that older drugs such as amoxycillin and piperacillin have low MICs against pneumococci, and may therefore be effective in the treatment of infection due to penicillin-intermediate and possibly even penicillin-resistant strains. PMID- 7861214 TI - An additional therapeutic effect of adequate hyperventilation in severe acute brain trauma: normalization of cerebral glucose uptake. AB - In a total of 309 frequent serial studies, arteriojugular differences in glucose and oxygen levels were concurrently evaluated in 33 adult patients who were experiencing the most acute phase of severe brain trauma. Hyperventilation therapy was optimized to maintain both normalized intracranial pressure and cerebral extraction of oxygen. Under these circumstances, global cerebral glucose extraction was found to be closest to normal during profound optimized hyperventilation, with PaCO2 levels below 25 mm Hg. In contrast, during normocapnia global cerebral glucose extraction dropped below normal range, indicating impairment of cerebral glucose uptake. Findings from this study show that in severe acute brain injury, optimized hyperventilation exerts an additional metabolic effect with respect to cerebral glucose uptake. PMID- 7861215 TI - Cerebrovascular carbon dioxide reactivity assessed by intracranial pressure dynamics in severely head injured patients. AB - Appropriate management of intracranial pressure (ICP) in severely head injured patients depends in part on the cerebral vessel reactivity to PCO2; loss of CO2 reactivity has been associated with poor outcome. This study describes a new method for evaluating vascular reactivity in head-injured patients by determining the sensitivity of ICP change to alterations in PCO2. This method was combined with measurements of the pressure volume index (PVI), which allowed calculation of blood volume change necessary to alter ICP. The objective of this study was to investigate the ICP response and the blood volume change corresponding to alterations in PCO2 and to examine the correlation of responsivity and outcome as measured on the Glasgow Outcome Scale. The PVI and ICP at different end-tidal PCO2 levels produced by mild hypo- and hyperventilation were obtained in 49 patients with Glasgow Coma Scale scores of less than 8 and over a wide range of PCO2 (25 to 40 mm Hg) in eight patients. Given the assumption that the PVI remained constant during alteration of PaCO2, the estimated blood volume change per torr change of PCO2 was calculated by the following equation: BVR = PVI x delta log(ICP)/delta PCO2, where BVR = blood volume reactivity. The data in this study showed that PVI remained stable with changes in PCO2, thus validating the assumption used in the blood volume estimates. Moreover, the response of ICP to PCO2 alterations followed an exponential curve that could be described in terms of the responsivity indices to capnic stimuli. It was found that responsivity to hypocapnia was reduced by 50% compared to responsivity to hypercapnia measured within 24 hours of injury (p < 0.01). The sensitivity of ICP to estimated blood volume changes in patients with a PVI of less than 15 ml was extremely high with only 4 ml of blood required to raise ICP by 10 mm Hg. The authors conclude from these data that, following traumatic injury, the resistance vessels are in a state of persistent vasoconstriction, possibly due to vasospasm or compression. Furthermore, BVR correlates with outcome on the Glasgow Coma Scale, indicating that assessment of cerebrovascular response within the first 24 hours of injury may be of prognostic value. PMID- 7861216 TI - Intramedullary spinal cord lipomas. AB - Spinal cord lipomas are rare lesions, accounting for approximately 1% of all spinal cord tumors. True intramedullary spinal cord lipomas are extremely rare and are represented in the literature as scattered, single case reports. The authors present a series of six patients with intramedullary spinal cord lipomas managed at our institution from July, 1985 to July, 1993. The patients' ages ranged from 8 to 45 years. Four patients presented with newly diagnosed tumors and two had undergone previous surgery. Patients usually presented with long histories of disability followed by rapid progression of their symptoms. Most patients were in poor neurological condition on presentation. Presenting symptoms included spinal pain, dysesthetic sensory changes, gait difficulties, weakness, and incontinence. Three patients had cervical tumors, two had cervicothoracic tumors, and one patient had a thoracic tumor. Diagnostic studies, including magnetic resonance imaging, were obtained in all patients. No patient exhibited any form of spinal dysraphism or had a dural defect. All patients underwent decompressive, subtotal resections of 40% to 70% of their lesions. Follow-up times ranged from 12 to 96 months. All patients had resolution of their pain, but they generally showed no neurological improvement. As of their most recent follow up visit, none of the patients was neurologically normal; three can function independently, although with neurological deficits. The other three patients cannot function independently and have severe neurological deficits. The authors conclude that patients with intramedullary spinal cord lipoma who present with significant neurological compromise have a very poor prognosis with regard to neurological function and generally show no improvement with surgical resection. PMID- 7861217 TI - Continuous intraoperative electromyographic recording during spinal surgery. AB - One hundred fifty patients underwent spinal surgery for radiculopathy; of these, 120 underwent lumbar surgery and 30 had cervical operations. All of the surgeries were performed to alleviate symptoms due to disc herniation, spondylosis, or both. During the surgical procedures continuous intraoperative electromyograph recordings were taken from the muscle corresponding to the involved nerve root. In baseline recordings taken in the operating room 10 minutes before lumbar surgery, electrical discharge or firing was recorded from the muscle in 18% (22 of 120 patients) of the cases. Once the nerve was decompressed, muscle firing ceased. Electrical discharges were produced with regularity on nerve root retraction. This study concludes that continuous electromyograph monitoring can be accomplished easily and yields valuable information that indicates when the nerve root is adequately decompressed or when undue retraction is exerted on the root. PMID- 7861218 TI - A clinicopathological study of collagen sponge as a dural graft in neurosurgery. AB - There is frequently a need for dural grafts to cover defects resulting from retraction, shrinkage, or excision following neurosurgical procedures. Several materials have been evaluated both experimentally and clinically, and then discarded. Collagen, in its various forms, continues to be an area of intense interest. In this study the authors examined the suitability of collagen sponge to effect dural repair. In a 5-year clinical study 102 collagen sponge implants were examined macroscopically and histologically. Graft encapsulation, neomembrane formation, delayed hemorrhage, and foreign body reactions were not found. The porous nature of the collagen sponge encouraged fibroblastic ingrowth and dural repair. Meningocerebral adhesions were present in 11 patients, all of whom had required significant cortical resection or had pia-arachnoid disruption during the initial surgery. Inflammatory cells were seen only in response to infection. Postoperative cerebrospinal fluid leaks developed in only three of 67 patients who underwent an intradural posterior fossa procedure. In a prospective arm of the study involving 459 patients, the wound infection rate using collagen sponge was 6.1%, which compared favorably (p = 0.67) with the 5.7% rate in a similar group of 637 patients in whom collagen sponge had not been used. PMID- 7861219 TI - Prospective double-blind placebo-controlled randomized trial on the use of ranitidine in preventing postoperative gastroduodenal complications in high-risk neurosurgical patients. AB - To determine the efficacy of ranitidine in preventing clinically acute overt gastroduodenal (GD) complications (bleeding and/or perforation) after neurosurgery, 101 patients with nontraumatic cerebral disease considered at high risk of developing postoperative GD complications were randomized in a standard double-blind manner to receive either ranitidine (50 mg every 6 hours) or placebo medication preoperatively. Postoperative serial GD endoscopy was used to document the occurrence of complications: an overt symptomatic complication was defined as bleeding requiring blood transfusion and/or surgery. Fifty-two patients received ranitidine and 49 received a placebo preoperatively; 30 developed overt GD bleeding; nine of these received ranitidine and 21 received a placebo. Ranitidine significantly reduced the incidence of bleeding (p < 0.05). Multivariate logistic regression analysis revealed three factors of independent significance in predicting overt GD bleeding: use of a placebo drug, a gastric pH of less than 4, and a high daily volume of gastric output. The authors conclude that ranitidine is useful in preventing postoperative GD complications in high-risk neurosurgical patients. PMID- 7861220 TI - Interstitial radiosurgery of low-grade gliomas. AB - The treatment of patients with low-grade gliomas remains a subject of controversy, especially with respect to new treatment modalities such as interstitial radiosurgery (brachytherapy), radiosurgery, and stereotactic radiotherapy. In a retrospective analysis conducted between 1979 and 1991, the authors studied the results of interstitial radiosurgery in 455 patients with low grade gliomas (World Health Organization (WHO) Grade I+WHO Grade II) with regard to survival time, quality of life, the risk of malignant transformation, and the risk profile of the treatment concept. Interstitial radiosurgery with iodine-125 was performed using permanent (1979-1985) or temporary implants (after 1985) with low-dose rates (< or = 10 cGy/hr) and a reference dose of 60 to 100 Gy calculated to the outer rim of the tumor. The 5- and 10-year survival rates in patients with pilocytic astrocytomas (97 patients) were 84.9% and 83%, and in patients with WHO Grade II astrocytomas (250 patients) 61% and 51%, respectively. Five-year survival rates for patients with oligoastrocytomas (60 patients), oligodendrogliomas (27 patients), and gemistocytic astrocytomas (21 patients) were 49%, 50%, and 32%, respectively. In the group with WHO Grade II gliomas, young age and a good performance status were associated with a better prognosis. Unfavorable factors were midline shift, enhancement on computerized tomography (CT) scan, and tumor recurrence after previous radiotherapy or surgery. Tumor location had no influence on the prognosis (247 patients in this series had deep seated tumors). Malignant transformation was the major cause of death. Important risk factors for malignancy were the patient's age, tumor enhancement in CT scan, and tumor recurrence after previous surgery or radiotherapy. Perioperative mortality was 0.9% and perioperative morbidity was 1.7%. Radiogenic complications were observed in 2.7% of all patients, most often in larger tumors and after using permanent implants. The authors conclude that interstitial radiosurgery represents a specific treatment modality for selected patients with unifocal circumscribed low-grade gliomas with a diameter of less than 4 cm in any location. The efficacy of this treatment lies in the same range as the best results after surgery and radiotherapy. PMID- 7861221 TI - Phase II evaluation of recombinant interferon alpha and BCNU in recurrent glioma. AB - The goal of this study was to determine the antitumor activity and toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) plus recombinant interferon-alpha (IFN-alpha) in patients with recurrent glioma. As single agents, both BCNU and IFN-alpha can cause tumor regression in patients with recurrent glioma. In vitro studies suggest synergy between the two agents. Thirty-five patients in whom computerized tomography (CT) or magnetic resonance (MR) evidence was obtained of progressive astrocytoma, oligoastrocytoma, or oligodendroglioma received recombinant IFN-alpha 2a (12 x 10(6) U/m2 intramuscularly) on Days 1 through 3 and BCNU (150 mg/m2 intravenously) on Day 3 of each 6-week cycle. All patients had tumor progression despite radiation therapy and had received no prior chemotherapy. Response was assessed by CT or MR evidence and by neurological examination while the patients were on a regimen of stable or decreasing doses of corticosteroids. All patients could be evaluated for response and toxicity. Twenty-nine percent of the patients demonstrated objective tumor regression; 37% remained stable for more than 6 months and 25% were stable for less than 6 months. The median duration of response to IFN-alpha and BCNU was 9.9 months and the median survival for all patients was 13.3 months. Toxicity consisted primarily of moderate myelosuppression, venous irritation, vomiting, flulike symptoms, and transient reversible exacerbation of underlying neurological symptoms. The use of BCNU plus IFN-alpha is a safe, active regimen in the treatment of patients with recurrent glioma who have failed to respond to prior radiation therapy. The contribution of IFN to the antitumor activity observed in this study compared with that previously described with BCNU alone cannot be assessed from this trial. PMID- 7861222 TI - Radiation necrosis or glioma recurrence: is computer-assisted stereotactic biopsy useful? AB - Fifty-one patients with supratentorial glioma treated with external beam radiotherapy (median dose 59.5 Gy) who then demonstrated clinical or radiographic evidence of disease progression underwent stereotactic biopsy to differentiate tumor recurrence from radiation necrosis. The original tumor histological type was diffuse or fibrillary astrocytoma in 21 patients (41%), oligodendroglioma in 13 (26%), and oligoastrocytoma in 17 (33%); 40 tumors (78%) were low-grade (Kernohan Grade 1 or 2). The median time to suspected disease progression was 28 months. Stereotactic biopsy showed tumor recurrence in 30 patients (59%), radiation necrosis in three (6%), and a mixture of both in 17 (33%); one patient (2%) had a parenchymal radiation-induced chondroblastic osteosarcoma. The tumor type at stereotactic biopsy was similar to the original tumor type and was astrocytoma in 24 patients (47%), oligodendroglioma in eight (16%), oligoastrocytoma in 16 (31%), unclassifiable in two (4%), and chondroblastic osteosarcoma in one patient (2%). At biopsy, however, only 19 tumors (37%) were low grade (Kernohan Grade 1 or 2). Subsequent surgery confirmed the stereotactic biopsy histological findings in eight patients. Follow-up examination showed 14 patients alive with a median survival of 1 year for the entire group. Median survival times after biopsy were 0.83 year for patients with tumor recurrence and 1.86 years for patients with both tumor recurrence and radionecrosis; these findings were significantly different (p = 0.008, log-rank test). No patient with radiation necrosis alone died. Other factors associated with reduced survival were a high proportion of residual tumor (p = 0.024), a low proportion of radionecrosis (p < 0.001), and a Kernohan Grade of 3 or 4 (p = 0.005). In conclusion, in patients with previously irradiated supratentorial gliomas in whom radionecrosis or tumor recurrence was clinically or radiographically suspected, results of stereotactic biopsy could be used to differentiate tumor recurrence, radiation necrosis, a mixture of both lesions, or radiation-induced neoplasm. In addition, biopsy results could predict survival rates. PMID- 7861223 TI - Diagnostic yield of stereotactic brain biopsy guided by positron emission tomography with [18F]fluorodeoxyglucose. AB - The aim of the present study was to determine whether routine integration of positron emission tomography (PET) with 18F-labeled fluorodeoxyglucose (FDG) in the planning of stereotactic brain biopsy increases the technique's diagnostic yield. Forty-three patients underwent combined FDG-PET- and computerized tomography (CT)-guided stereotactic biopsy of intracranial lesions according to a previously described technique. In 36 patients, an area of abnormal FDG uptake was used to guide at least one stereotactic biopsy trajectory. A total of 90 stereotactic trajectories were performed; among them, 55 were based on FDG-PET defined targets and 35 were based on CT-defined targets. Histological diagnosis was obtained in all patients, but six of the 90 trajectories were nondiagnostic; all six were based on targets defined by CT only. Differences between the diagnostic yield of trajectories based on FDG-PET-defined targets and those based on CT-defined targets were statistically significant in patients with contrast enhanced lesions, but not in patients with nonenhancing lesions. These results support the view the FDG-PET may contribute to the successful management of brain tumor patients requiring stereotactic biopsy. Because no significant increase in discomfort or morbidity related to the technique was found, it is suggested that the development of similar techniques integrating PET data in the planning of stereotactic biopsy should be considered by centers performing stereotactic surgery and having access to PET technology. PMID- 7861224 TI - Androgen receptor expression in meningiomas. AB - The predominance of meningiomas in females, the accelerated growth of these tumors during the luteal phase of the menstrual cycle and during pregnancy, and the association between meningiomas and breast cancer have led to a number of studies examining the potential role of steroids in the growth of meningiomas. The possibility that androgens play a role in meningioma proliferation has been suggested by a small number of investigators. The aim of this study was to examine the expression of androgen receptor messenger ribonucleic acid (mRNA) and correlate it using immunochemistry with the nuclear localization of androgen receptor in a large number of meningiomas. Thirty-nine meningiomas were examined by Northern blot analysis for the presence of measurable amounts of androgen receptor mRNA and eight of these were analyzed by immunohistochemistry for receptor protein. Sixty-seven percent of the meningiomas expressed androgen receptor mRNA. There was a marked predominance of women among the patients whose tumors expressed androgen receptor; 69% were women and 31% were men. The immunohistochemical data correlated with Northern blot analysis of mRNA. The staining was predominantly nuclear, suggesting that the androgen receptor resides in a location that can activate gene expression. PMID- 7861225 TI - Paradoxical elevation of Ki-67 labeling with protein kinase inhibition in malignant gliomas. AB - The monoclonal antibody Ki-67 recognizes a nuclear antigen expressed in the G1, S, G2, and M phase of the cell cycle and has been used extensively as an indicator of cellular proliferation in malignant gliomas, both in the laboratory and clinically. Recently, protein kinase C (PKC) inhibitors have been demonstrated to inhibit malignant glioma growth both in in vitro and in vivo. This study was undertaken to determine whether Ki-67 could function as an indicator of cellular proliferation rate after PKC inhibition in gliomas and to explore cell cycle specificity of such inhibition. Both established and low passage malignant glioma cell lines have previously been shown to be sensitive to growth inhibition by the PKC inhibitors staurosporine and tamoxifen in vitro (IC50 in the nanomolar and micromolar ranges, respectively), as measured by cell numbers, [3H]thymidine uptake, and flow-cytometric DNA analysis. However, in the same cells that are inhibited by staurosporine and tamoxifen on these assays, and on the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay in the present study, the Ki-67 labeling index paradoxically increased in a dose related manner with the same treatments, as measured by immunohistochemistry and confirmed by flow cytometry. For example, in established line U-87, a 20.5% decrease in thymidine uptake and a 28.5% decrease in absorbance on the MTT assay produced by tamoxifen at 1 microM was associated with an increase in Ki-67 labeling from 42% to 62%; staurosporine, which produces a 78.8% decrease in thymidine uptake in cell line A-172 at 10 nM, produced an increase in Ki-67 labeling from 19% to 32%. In this regard, Ki-67 labeling of glioblastoma tissue from a patient treated with high-dose tamoxifen yielded results within the range of 10% to 15% (consistent with values seen in untreated glioblastoma), despite tumor regression with treatment. The authors' interpretation of these results is that these PKC inhibitors are halting the cell cycle in the G1 phase or the G1-S transition (beyond G0 but before S-phase), resulting in a paradoxical increase in labeling while arresting growth. Two important implications from these observations are that Ki-67 is not a reliable indicator of cellular proliferation after treatment with PKC inhibitors and that these inhibitors used at the doses given above halt cell growth in a phase-specific manner. PMID- 7861226 TI - Combination therapy with cisplatin and nifedipine inducing apoptosis in multidrug resistant human glioblastoma cells. AB - The authors found that multidrug-resistant human glioblastoma GB-1 cells demonstrated significantly more resistance to cisplatin than did nondrug resistant human glioblastoma U87-MG cells (p < 0.1). They therefore attempted to determine whether calcium channel blockers enhance the antitumor activity of cisplatin against GB-1 cells. Nifedipine, a dihydropyridine calcium channel blocker, significantly enhanced the antitumor effect of cisplatin on GB-1 cells (p < 0.05). In the absence of normal extracellular Ca++, nifedipine enhanced the cytotoxicity of cisplatin. In addition, the antitumor activity of combined cisplatin and nifedipine was inhibited both by actinomycin D and cycloheximide, suggesting that such activity is dependent upon new RNA and protein synthesis. Surprisingly, DNA fragmentation assay demonstrated that synergism between cisplatin and nifedipine resulted in apoptosis (programmed cell death) at a relatively low concentration of cisplatin, which when tested alone did not induce apoptosis. In addition, it was demonstrated that nuclei from GB-1 cells lacked a Ca(++)-dependent endonuclease that degrades chromatin into nucleosomes and that calcium ionophore A 23187 did not decrease the viability of GB-1 cells. The above findings suggest the hypothesis that the noncytotoxic agent nifedipine synergistically enhances the antitumor effect of cisplatin on multidrug-resistant GB-1 cells lacking Ca(++)-dependent endonuclease, and subsequently induces apoptosis via its interaction with an as yet uncharacterized functional site other than the calcium channel on GB-1 cells. PMID- 7861227 TI - Human monoclonal antibody BT32/A6 and a cell cycle-independent glioma-associated surface antigen. AB - The purpose of this study was to ascertain how various growth parameters may influence the labeling of SK-MG-1, a human glioma cell line, by BT32/A6, a human immunoglobulin M monoclonal antibody (MAb). By growing SK-MG-1 cells at different culture split ratios, significant trends in cell growth rate, culture viability, and cell cycle state were produced. Labeling of SK-MG-1 cells by BT32/A6, however, was shown to be unaffected by culture split ratio (p > 0.05) and is therefore independent of cell growth rate, culture viability, and cell cycle state. Using flow cytometry and fluorescence-activated cell sorting, BT32/A6 was shown to label a cell surface antigen on viable, clonogenic cells of SK-MG-1. Approximately 100% of SK-MG-1 cells were shown by flow cytometry to express the BT32/A6 antigen. The recognition of a glioma-associated, cell cycle-independent surface antigen by MAb BT32/A6 makes it a promising candidate for further studies aimed at elucidating its usefulness as an adjunct in the treatment of human malignant gliomas. PMID- 7861228 TI - Effectiveness of controlled release of a cyclophosphamide derivative with polymers against rat gliomas. AB - Most malignant gliomas grow despite treatment by standard chemotherapeutic agents. The authors explored the use of an innovative drug, 4 hydroperoxycyclophosphamide (4HC), delivered via a controlled-release biodegradable polymer to determine whether local delivery would enhance efficacy. This drug is an alkylator-type chemotherapeutic agent derived from cyclophosphamide. Unlike the parent drug, which requires activation by hepatic microsomes, 4HC is active in vitro. Two rat glioma cell lines, 9L and F98, were treated in cell culture with medium containing 4HC. Both cell lines were more sensitive to 4HC than to a nitrosourea, BCNU, an agent of established value in the local therapy of gliomas. Ninety Fischer 344 rats implanted with 9L or F98 gliomas were treated with an intracranial polymer implant containing 0% to 50% loaded 4HC in the polymer, and it was found that 20% 4HC-loaded polymers caused minimum local brain toxicity and maximum survival. These polymers were then used to compare the in vivo efficacy of 4HC to BCNU in rats implanted with 9L glioma. Animals with brain tumors treated with 4HC had a median survival span of 77 days compared to the median survival of 21 days in BCNU-treated animals and median survival of 14 days in untreated animals. Long-term survival for more than 80 days was 40% in the 4HC-treated rats versus 30% in the BCNU-treated rats. The polymer carrier used in this study was a copolyanhydride of dimer erucic acid and sebacic acid 1:1, which was able to maintain the hydrolytically unstable 4HC in a stable state for local delivery. Thus, it is concluded that 4HC-impregnated polymers provide an effective and safe local treatment for rat glioma. PMID- 7861229 TI - Radiation-induced meningioma with a 63-year latency period. Case report. AB - Meningiomas are known to be induced by low-, moderate-, and high-dose radiation therapy, with an average time interval to tumor appearance of 35, 26, and 19 to 24 years, respectively. An inverse relationship is suggested between the dose of radiation given and the time to tumor formation. The authors report a case of a 68-year-old woman who received orthovoltage radiotherapy at 5 years of age for a presumed (nonbiopsy confirmed) right cerebellar tumor and developed multiple meningiomas in the radiation portals 63 years later. Like many radiation-induced meningiomas, the tumor was histologically atypical and multiple in its presentation. This case suggests that previous radiotherapy may confer a low, but life-long, risk for meningioma occurrence. PMID- 7861230 TI - Carcinoembryonic antigen production associated with an osteolytic meningioma. Case report. AB - An elevated serum carcinoembryonic antigen (CEA) without evidence of neoplasia was noted in an 84-year-old woman. She subsequently developed a lytic skull lesion, which at surgery proved to be an atypical meningioma. Immunohistochemical analysis demonstrated that this tumor was producing CEA. This aggressive meningioma required two further resections and adjuvant radiotherapy in the following 18 months. Serum elevation of CEA has been reported only twice in association with meningiomas; both of those tumors were of the secretory subtype. PMID- 7861231 TI - Isolated toxoplasmosis of the thoracic spinal cord in a patient with acquired immunodeficiency syndrome. Case report. AB - Toxoplasmosis and lymphoma are the two most common causes of intraparenchymal cerebral mass lesions in patients with acquired immunodeficiency syndrome (AIDS). The clinical and radiographic features of the intracranial lesions have been well described. Because of the high frequency of toxoplasmosis in the AIDS population, common therapy for patients presenting with intracranial mass lesions consists of an empirical trial of anti-Toxoplasma chemotherapy, with biopsy reserved for cases demonstrating features considered to be more consistent with lymphoma, or for lesions that do not improve despite adequate anti-Toxoplasma treatment. A similar treatment algorithm does not exist for intramedullary lesions of the spinal cord. The authors describe a patient who presented with paraparesis resulting from an isolated thoracic intramedullary lesion. An open biopsy of the lesion revealed characteristic structures containing Toxoplasma tachyzoites. The clinical and radiographic presentation of the lesion is discussed, the available literature is reviewed, and a treatment strategy for spinal cord lesions in AIDS patients is proposed. PMID- 7861232 TI - Tonsillar ectopia and Chiari malformations: monozygotic triplets. Case report. AB - A unique case of monozygotic triplets, each of whom exhibits variable degrees of tonsillar ectopia, is reported. Patient X presented with a Chiari I malformation and associated syringomyelia; examination of patients Y and Z showed 4 mm and 2.5 mm of tonsillar ectopia, respectively. No such case has been reported in the literature. The discussion defines the current magnetic resonance criteria for diagnosis of hindbrain malformations and addresses the question of whether these disorders represent a spectrum or separate disease entities, with specific emphasis on genetic predisposition. Due to the 100% concordance in this case the presence of a common hereditary factor in the etiology of these malformations is highly suggested. PMID- 7861233 TI - Control of persistent hemiballismus by chronic thalamic stimulation. Report of two cases. AB - Persistent hemiballismus after stroke is often difficult to treat. The ballistic movement is sometimes so violent that progressive exhaustion results. The authors report two such cases, which were successfully treated by chronic thalamic stimulation. The lesions responsible for the ballistic movement in these patients were located near the subthalamic nucleus and in the putamen, respectively. The thalamic nucleus ventrolateralis and nucleus ventralis intermedius were stimulated with 0.2 to 0.3 msec pulses at 50 to 150 Hz and 4 to 7 V continuously during the day. Several weeks later, complete control of the hemiballismus was achieved during stimulation. The improvement was clearly not attributable to spontaneous recovery, because ballistic movement reappeared after termination of the stimulation. The stimulation has remained effective for more than 16 months in both cases without any serious complications. Chronic thalamic stimulation appears to be useful for controlling persistent hemiballismus, as it is for other involuntary movement disorders. PMID- 7861234 TI - Total recanalization of a spontaneously thrombosed arteriovenous malformation. Case report. AB - The authors describe what they believe to be the first case of an asymptomatic, totally recanalized arteriovenous malformation (AVM) demonstrated by angiography 31 months after complete spontaneous thrombosis. The AVM, which initially became symptomatic with bleeding, had a 2-cm diameter nidus that was located within the inferior aspect of the left frontal lobe and was fed by branches from the left anterior cerebral and anterior ethmoid arteries. A single draining vessel flowed from the nidus into the anterior superior sagittal sinus. The AVM was surgically extirpated after recanalization. The authors stress the necessity for follow-up care for angiographically "cured" AVMs. PMID- 7861235 TI - Preoperative magnetic resonance imaging localization of convexity brain lesions. Technical note. AB - The authors present a simple and accurate new technique for preoperative localization of convexity lesions of the brain by means of magnetic resonance (MR) imaging. This method uses measurements from the initial diagnostic MR image and provides precise intraoperative guidance to cortical and subcortical cerebral lesions. PMID- 7861236 TI - Preoperative localization of brain lesions by magnetic resonance imaging with a marking device. Technical note. AB - A new technique for preoperative localization of brain lesions using magnetic resonance imaging and a marking device is described. The projection of lesions, especially superficial brain tumors, is demonstrated on the scalp, with an acceptable tolerance for open procedures. This simple and inexpensive method, which was use in a group of 34 patients, can assist surgeons in planning an operative approach to intracranial lesions. PMID- 7861237 TI - Spinal cord tumors in children. PMID- 7861238 TI - Chemotherapy and meningiomas. PMID- 7861239 TI - Neurosurgery at the Mount Sinai Hospital. PMID- 7861240 TI - Treatment of trauma-induced amnesia. PMID- 7861241 TI - Eijkman's contribution to the discovery of vitamins. AB - The work by Christiaan Eijkman in Batavia (now Djakarta, the capital of Indonesia) between 1890 and 1900, for which he received a Nobel Prize, is reviewed. While searching for a microorganism responsible for beriberi, he found that a condition of polyneuritis, with similarities to beriberi, could be produced consistently in chickens by feeding them polished rice, and that addition of the silverskin removed during polishing prevented this. He showed further that the silverskin did not act by physically preventing the entry of microorganisms into the endosperm, nor was its action explained by the protein and salts that it contributed. His tentative hypothesis was that this fraction contributed an antidote to a nerve poison produced by the fermentation of starch in the chickens' crop. However, his successor continued to use Eijkman's animal model and was able to show that silverskin supplied some unknown factor(s) that was required regardless of whether or not the diet contained starch. Fractionation eventually showed thiamin to be the active factor. PMID- 7861242 TI - A fructose-rich diet decreases insulin-stimulated glucose incorporation into lipids but not glucose transport in adipocytes of normal and diabetic rats. AB - To study the cellular mechanisms underlying fructose-induced insulin resistance in rats, the effects of fructose feeding on insulin-stimulated glucose transport, oxidation and incorporation into lipids in epididymal adipocytes were evaluated in 27 normal and 27 noninsulin-dependent diabetic male Sprague-Dawley rats. Diabetes was induced by streptozotocin injection 2 d after birth. At 5 wk of age, both normal and diabetic rats were fed a diet containing 62% carbohydrate as fructose, dextrose or cornstarch. Fructose feeding for 6 wk induced glucose intolerance in normal rats (P < 0.05) and aggravated that of diabetic rats (P < 0.05). Plasma triacylglycerol concentration was higher in fructose-fed than in starch-fed or dextrose-fed rats (P < 0.05). Adipocytes of fructose-fed rats had significantly lower maximum insulin-stimulated glucose incorporation into total lipids than those of rats fed starch, and tended (P = 0.22) to have lower production of CO2 from glucose than adipocytes of the other dietary groups. Glucose transport in adipocytes of dextrose-, starch- and fructose-fed rats did not differ. We conclude that in both normal and diabetic rats, a chronic fructose rich diet induced hypertriacylglycerolemia, glucose intolerance and insulin resistance of adipocytes. PMID- 7861243 TI - Apolipoprotein A-I synthesis and secretion are increased in Hep G2 cells depleted of copper by cupruretic tetramine. AB - Two amine chelators, namely N,N'-bis(2-aminoethyl)-1,3-propanediamine-4 HCl (2,3,2-tetramine) and diamsar, were used at various levels to deplete copper (Cu) from cultured Hep G2 cells. For cells cultured at 0.63 mumol of Cu/L, maximal depletions were attained after 24 h of incubation with 10 mumol of either chelator/L, which resulted in an average significant depletion of 45% of cellular Cu. In addition, when cells were cultured continuously for four passages at 0.63 mumol Cu/L with 20 mumol of 2,3,2-tetramine/L, cellular Cu was significantly depleted more than 40% compared with controls. Furthermore, after two passages of 2,3,2-tetramine treatment, cells were pulsed for 10 min with [3H]leucine and chased up to 2 h. At the end of the pulse, the amount of [3H]leucine incorporated into apolipoprotein A-I was twofold greater (P < 0.05) in treated than in control cells. No difference was detected for the synthesis of apolipoprotein B and total protein. During the chase, the cellular depletion curves for apolipoprotein A-I, apolipoprotein B and total protein were not altered by 2,3,2-tetramine treatment. From 30 to 120 min of the chase, the amount of nascent apolipoprotein A-I degraded was small and not altered, but that secreted into the medium was 56% higher (P < 0.05) in the Cu-depleted than in the control cells. PMID- 7861244 TI - Investigations into the actions of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1(7-36)amide on lipoprotein lipase activity in explants of rat adipose tissue. AB - The direct actions of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1(7-36)amide and insulin on lipoprotein lipase activity in explants of rat epididymal adipose tissues were investigated. Lipoprotein lipase was extracted into the incubation medium by heparin release of lipoprotein lipase and measured by fatty acid release from a glyceroltriolein emulsion. Insulin and glucose-dependent insulinotropic polypeptide caused a significant stimulation of lipoprotein lipase activity over a dose range of 0.25-4 nmol/L and 4-8 nmol/L, respectively. Explants incubated in the presence of both insulin and glucose dependent insulinotropic polypeptide (at 0.5 and 4 nmol/L, respectively) showed levels of lipoprotein lipase activity significantly greater than that seen with either hormone alone. Neither insulin- nor glucose-dependent insulinotropic polypeptide-stimulated lipoprotein lipase was modified by the presence of the antibiotic actinomycin-D in the incubation medium, indicating that these two hormones exert their actions on the pre-existing cellular pool of lipoprotein lipase. Glucagon-like polypeptide-1(7-36)amide, over a dose range of 1-8 nmol/L, did not stimulate lipoprotein lipase activity. This study indicates that glucose dependent insulinotropic polypeptide, in addition to stimulating insulin secretion, has a direct biological action on adipose tissue and in vivo, together with insulin, may promote lipoprotein lipase activity postprandially. PMID- 7861245 TI - The thiamine-dependent hysteretic behavior of human transketolase: implications for thiamine deficiency. AB - We have investigated the hysteretic properties of human transketolase with emphasis on its dependency on thiamine pyrophosphate concentration. As demonstrated previously, the reaction progress curves revealed a slow transition from an initial low velocity to a faster final steady-state velocity, characterized by the rate constant tau-1. The rate of the transition was dependent on the concentration of the thiamine pyrophosphate cofactor, with progressively longer transition times found as the concentration of thiamine pyrophosphate was decreased. At physiological thiamine pyrophosphate concentrations, the inverse rate constant was in the range of 10 to 20 min for fibroblast-derived transketolase and increased dramatically with only small decreases from these levels of thiamine pyrophosphate. Variation in the lag was found when transketolase from different individuals was examined. Moreover, at low levels of thiamine, the rate of the transition was different between fibroblast- and lymphoblast-derived transketolase. The substantial lag in formation of active holoenzyme and the findings of interindividual variation and cell type variation in the lag period suggest mechanisms for the loss of transketolase activity during thiamine deficiency and may explain, at least in part, the differential sensitivity to deficiency demonstrated by tissues and individuals. PMID- 7861246 TI - Activities of antioxidant enzymes in various tissues of male Fischer 344 rats are altered by food restriction. AB - The objective of this study was to determine how food restriction (40% restriction of food intake) altered the age-related changes in the activities of Cu,Zn superoxide dismutase, catalase and glutathione peroxidase in liver, brain cortex, heart, kidney and intestinal mucosa obtained from 6-, 16- and 26-mo-old male Fischer 344 rats. Food restriction increased the activity of one or more of the antioxidant enzymes in the liver, brain cortex, heart and kidney of the rats. However, the magnitude of the effect and the antioxidant enzyme(s) affected by food restriction varied from tissue to tissue, and food restriction had no significant effect on the activities of these enzymes in intestinal mucosa. Interestingly, the four tissues in which food restriction increased the activity of one or more of the antioxidant enzymes showed reduced lipid peroxidation as measured by thiobarbituric acid-reactive material. These data suggest that food restriction might enhance the survival of rodents by altering the levels of the antioxidant enzymes and hence reducing free radical damage. PMID- 7861247 TI - Vitamin A supplementation does not improve growth of preschool children: a randomized, double-blind field trial in south India. AB - A randomized, double-blind, placebo-controlled trial was conducted in an ongoing growth monitoring research project in TamilNadu, India, to assess the role of high dose vitamin A supplementation on the growth of mild to moderately malnourished children < 3 y old. The treatment group received 60 mg of vitamin A and the control group received a placebo every 4 mo. Infants 6-11 mo of age received only 30 mg of vitamin A Cases of xerophthalmia and severe malnutrition were excluded. Anthropometric measurements and serum retinol determinations were made at baseline and at the end of 1 y. The two groups were similar at baseline in nutritional status, serum retinol, age-sex composition and other socio demographic indicators. The mean height increments were 9.20 +/- 3.51 and 9.01 +/ 3.41 cm/y for the vitamin A-treated (n = 310) and placebo (n = 282) groups, respectively, and the mean weight increments were 2.02 +/- 0.83 and 1.99 +/- 0.81 kg/y, respectively. The differences in growth increments between the two groups were not statistically significant. These findings remain unaltered following multivariate analysis and suggest the lack of an effect of vitamin A supplementation on growth in young children where access to health care and immunization are good. PMID- 7861248 TI - A vegetarian diet rich in soybean products compromises iron status in young students. AB - The iron status of young Chinese Buddhist vegetarians (23 men and 32 women) and nonvegetarian students (20 men and 39 women from a medical college) was investigated by dietary assessment of iron intake and hematological measurement of biochemical indices including hemoglobin, plasma iron, transferrin, transferrin saturation and plasma ferritin. A characteristic of the vegetarian diet in this study was the replacement of meat by soybean products. Results of the dietary assessment showed that the average iron density of the diets ranged from 1.9 to 2.2 mg/MJ, with no difference between the vegetarian and nonvegetarian diets. Daily iron intake was similar in both vegetarian and nonvegetarian men. However, iron intake was significantly higher in female vegetarians than nonvegetarians, averaging 104 and 78% of the RDA, respectively. Results of blood analysis showed that, for both sexes, the median plasma ferritin concentration of the vegetarians (male 47 micrograms/L and female 12 micrograms/L) was about half the level of the nonvegetarians (male 91 micrograms/L and female 27 micrograms/L). Occurrence and risk of iron deficiency are more prevalent in vegetarians. Correlation between plasma ferritin concentration and years of vegetarian practice in vegetarian men was marginally significant (r = -0.38, P = 0.077). We conclude that a vegetarian diet that is rich in soybean products and restricted in animal foods is limited in bioavailable iron and is not adequate for maintaining iron balance in men and women. PMID- 7861249 TI - Closed-loop control of carbon dioxide concentration and pressure improves response of room respiration calorimeters. AB - Large room calorimeters are capable of rapid measurements that are usually made in hoods or small rooms. We evaluated the performance gains of four calorimeters constructed with modern control systems, sample gas preparation and data processing. Calibration of the calorimeters and instruments was performed in place, with traceability to international standards. Performance was evaluated by infusion of N2-CO2 gas and 243 24-h studies of individuals. Our subjects included children weighing 20 kg and adults engaged in heavy exercise. Errors for 24-h infusion measurements (n = 23) were -0.34 +/- 1.24% for oxygen consumption rate and 0.11 +/- 0.98% for carbon dioxide production rate. Calorimeter 90% response times were 2 to 6 min over a range of oxygen consumption rates from 100 to > 4000 mL/min. Closed-loop control of supply and exhaust air flows provided consistent 24-h mean CO2 levels (0.39 +/- 0.015%) and pressures (13.2 +/- 4.4 Pa). Room calorimeters operated with closed-loop control can be used for accurate measurement of energy expenditure rate dynamics for a wide range of individuals. PMID- 7861250 TI - The positional distribution of fatty acids in palm oil and lard influences their biologic effects in rats. AB - Dietary fatty acids in the sn-2 position are preferentially absorbed as monoacylglycerols. To determine whether thy also have more important biologic effects, rats were fed for 2 and 4 mo a purified diet containing native palm oil, interesterified palm oil, native lard or interesterified lard. Interesterification that increased or decreased the level of fatty acids in position 2 depending on the fat, resulted in significant corresponding changes in the fecal excretion of saturated fatty acids. Fecal excretion of saturated fatty acids was associated with significant changes in some plsma fatty acids. Interesterification in lard resulted in significantly lower plasma triglycerides, and in palm oil, increased platelet aggregation induced by ADP. Lipemia, platelet aggregation and associated plasma fatty acids (palmitic, heneicosanoic and docosahexaenoic acids) were significantly affected only by dietary fatty acids at the sn-2 position. Even without changes in absorption, only linoleic acid in position 2 was correlated with the plasma concentration of the corresponding longer chain arachidonic acid. These results in rats confirm that the fatty acids (saturated and unsaturated) in position 2 of dietary triglycerides play a crucial role in the metabolism and biologic effects of these fatty acids. PMID- 7861251 TI - Carnitine affects octanoate oxidation to carbon dioxide and dicarboxylic acids in colostrum-deprived piglets: in vivo analysis of mechanisms involved based on CoA- and carnitine-ester profiles. AB - Newborn, colostrum-deprived piglets (n = 21) were used to study the effects of L carnitine supplementation on the in vivo oxidation of [1-14C]octanoate to CO2 and dicarboxylic acids. Pigs were fitted with arterial and bladder catheters and were infused with octanoate (supplying 35-100% of piglets' energy expenditure) and with or without valproate for a period of 24 h. After achieving steady-state octanoate oxidation, carnitine was coinfused [50 mumol/kg 0.75 prime plus 20 mumol/h.kg 0.75)], and deviations in the octanoate oxidation rate, dicarboxylic acid excretion rate, and carnitine metabolism were monitored. At the end of the 24-h infusion, samples of liver and muscle were analyzed for carnitine- and CoA esters by HPLC. Carnitine stimulated octanoate oxidation by 7% (P < 0.05) and decreased dicarboxylic acid excretion by 45% (P < 0.05). Carnitine supplementation increased (P < 0.05) concentrations of carnitine and acetyl carnitine in hepatic tissue (three- and 55-fold, respectively) and plasma (seven- and 11-fold); whereas, muscle-carnitine concentration doubled upon carnitine supplementation, but acetyl carnitine concentration remained unaltered. Urinary excretion of acetyl and free carnitine also increased with carnitine supplementation, but accounted for < 10% of carnitine infused. Hepatic total CoA and CoA esters increased with carnitine supplementation, whereas muscle acetyl CoA decreased. Valproate had only marginal effects on octanoate metabolism. These data confirm the hypothesis that carnitine effects the in vivo oxidation of octanoate in colostrum-deprived piglets and suggest that the effects may be mediated by aiding the export of excess acetyl groups from muscle or by enhancing uptake of octanoate into liver mitochondria. PMID- 7861252 TI - Dietary arginine deficiency and gut ammonium infusion alter flux of urea cycle intermediates across the portal-drained viscera of pigs. AB - The objective of these experiments in pigs were to test the hypotheses that 1) gut synthetic processes could adapt to additional dietary glutamate or ornithine to meet tissue needs for arginine with feeding arginine-deficient diets and 2) acute elevation of ammonium in the hepatic-portal blood leads to increased glutamine production. Arterial [117 +/- 5.3 (arginine-deficient) vs. 78 +/- 5 (arginine-adequate) mumol/L] and portal ammonium concentrations were elevated in pigs fed arginine-deficient diets. Dietary ornithine, which elevated portal drained visceral flux of ornithine, corrected the urinary orotic aciduria, but not the hyperammonemia seen with feeding arginine-deficient diets. Concentrations or portal drained viscera fluxes of arginine, ornithine, glutamate and glutamine were not altered even though portal and arterial ammonium concentrations were increased 8- and 3.5-fold with mesenteric infusion of ammonium. It was concluded that 1) substitution of glutamate for glycine or alanine does not alter gut production of ornithine, citrulline or arginine; 2) gut citrulline production is not altered by levels of dietary arginine, ornithine or glutamate; 3) increased ammonium challenge does not lead to increased glutamine production even though peripheral ammonium levels increased over threefold; and 4) provision of arginine for tissue needs will have to be met from dietary sources, as adaptations in gut synthetic processes seem to be refractory to dietary arginine status. PMID- 7861253 TI - Contribution of D-(-)-3-hydroxybutyrate to the energy expenditure of neonatal pigs. AB - In vivo oxidation rate of arterially infused D-(-)-3-hydroxybutyrate (3HB) was measured in 1-2-d-old-piglets. Twelve piglets (1.4 kg) were randomly assigned to a 12 h continuous infusion of 3HB at 19.5, 37.8, 55.8 or 74.5 mumol/min along with -31 kBq/h of [3-14C]3HB. Piglets were housed in respiration chambers allowing collection of total expired CO2 over 20-min intervals for the 12 h infusion and 6 h washout. Oxidation of 3HB was calculated from the quantity and specific radioactivity of expired CO2 for 20-min collection periods at 6, 9 and 12 h for each piglet and collectively plotted against plasma 3HB concentration measured in blood drawn during those 20-min periods. A Lineweaver-Burk plot of these data yielded a Km of 0.62 +/- 0.07 mmol/L and Vmax of 0.74 +/- 0.02 mmol ATP equivalents/(min.kg 0.75) (parameter estimate +/- SD), which could account for 32% of the piglet mean total ATP turnover of 2.3 mmol/(min.kg 0.75). These data show that 3HB oxidation is a linear function of plasma concentration in the physiologic range measured in piglets (0.006 mmol/L to 0.1 mmol/L) and within this range would account for 0.3% to 4.5% of piglet energy requirement. Oxidation of 3HB can meet a maximum of 30 to 40% of piglet energy requirement at unphysiologically high 3HB concentrations (> 3 mmol/L). PMID- 7861254 TI - Dietary fiber increases oxidative metabolism in colonocytes but not in distal small intestinal enterocytes isolated from rats. AB - Colonocyte and distal small intestinal enterocyte metabolism was studied in rats fed either an elemental diet or an elemental diet supplemented with 30% mixed dietary fiber for 14 d. Cells were incubated in RPMI 1640 culture media containing 14C-labeled glutamine (1 mmol/L), glucose (11 mmol/L), and short-chain fatty acids: acetate, propionate and butyrate (5 mmol/L). Substrate oxidation and product formation were measured. Colonocytes from the fiber-fed group had 22-51% higher oxidation rates than the elemental-fed group for all substrates tested. The group consuming the fiber diet had 28% less glutamate formation from glutamine by isolated colonocytes than the group consuming the elemental diet. Enterocyte acetate oxidation and lactate formation rates were lower (60 and 30%) in the fiber-fed animals vs. the elemental-fed group. Including short-chain fatty acids and ketone bodies in incubation media differentially affected acetate, glutamine and glucose metabolism in isolated intestinal cells, depending on segment and diet. Short-chain fatty acid and glucose oxidation rates were higher for colonocytes than enterocytes and glutamate formation was greater in enterocytes than colonocytes. Fiber consumption increased this segmental disparity. This study demonstrates that dietary fiber consumption increases substrate oxidation by isolated colonocytes but not distal small intestinal enterocytes. PMID- 7861255 TI - Feeding Australian Acacia gums and gum arabic leads to non-starch polysaccharide accumulation in the cecum of rats. AB - Exudative gums from two Australian Acacia species (A. pycnantha and A. baileyana) and gum arabic (from A. senegal) were fed to rats at graded levels (0, 20, 40, 80 g/kg), replacing cellulose in purified diets containing cholesterol plus cholic acid. Compared with consumption of the control diet containing cellulose only, consumption of the gums had no significant effects on concentrations of plasma or liver cholesterol. Plasma triacylglycerol concentrations were higher in rats fed gum arabic, whereas liver triacylglycerols were lower in rats fed the gums. The gums did not affect the total pool of volatile fatty acids in the ceca, as compared with results in controls, but did promote the relative contribution of propionate at the expense of acetate. In rats fed the diet containing cellulose (80 g/kg) the proportions of cecal acetate:propionate:butyrate were 76:15:9, whereas in the rats fed A. pycnantha gum, gum arabic and A. baileyana gum (80 g/kg) the ratios were 42:54: 4, 35:46:19 and 43:53:4, respectively. The low apparent fermentability of the gums was confirmed by the accumulation of non starch polysaccharides in cecal digesta. In rats fed 80 g/kg A. pycnantha gum, 3.44 g of soluble non-starch polysaccharides was measured in the ceca, which was 58% of the dry weight of the cecal contents. We conclude that the biological activities of the Australian Acacia gums were similar to those of gum arabic and that these gums may have potential value as human food ingredients. PMID- 7861256 TI - Classical selenium-dependent glutathione peroxidase expression is decreased secondary to iron deficiency in rats. AB - While there are reports that classical selenium-dependent glutathione peroxidase (Se-GPX1) activity is decreased during iron deficiency, the relationship between tissue iron status and Se-GPX1 activity remains speculative. This study was undertaken to investigate the mechanism for the decrease in Se-GPX1 activity during iron deficiency. Male weanling Sprague-Dawley rats were given free access to either an iron-deficient or an iron-adequate diet for eight weeks, after which blood, livers, kidneys, hearts, brains and testes were surgically excised. During iron deficiency, Se-GPX1 mRNA levels in liver tissue were decreased by approximately 55%. Similarly, the concentration of immunoreactive Se-GPX1 protein and total selenium-dependent glutathione peroxidase (Se-GPX) activity were decreased by 55% and 60%, respectively. In kidney, heart and brain total Se-GPX activities were depressed as much as 33%. Selenium concentration in liver was reduced by 42%, whereas the decrease in Se concentrations in kidney, heart, and brain ranged from 17 to 25%. Concentrations of plasma Se also were reduced by 18%, but testes showed little change in either Se-GPX activity or Se concentration during iron deficiency. Results suggest that the synthesis of Se GPX1 protein is decreased during iron deficiency possibly due to pretranslational regulation. PMID- 7861257 TI - Selenium deficiency alters thyroid hormone metabolism in guinea pigs. AB - In guinea pigs, activity of glutathione peroxidase in most organs is markedly lower than in organs of other rodents despite comparable dietary intakes and tissue levels of selenium. To determine if metabolism of selenium with respect to other selenoproteins also differs in guinea pigs, we measured the effects of selenium intake on thyroid hormone metabolism. Weanling male Hartley Albino guinea pigs were fed a selenium-deficient Torula yeast-based diet, or the same diet supplemented with 0.5 mg selenium/kg diet as sodium selenate for 72 d. Growth was impaired in guinea pigs fed the unsupplemented diet. Activity of glutathione peroxidase was higher in tissues and plasma of supplemented guinea pigs than in selenium-deficient animals. However, it was still far lower than reported values for other rodent species. In selenium deficiency, activity of type 1 5'-iodothyronine deiodinase was 60% less in liver and 45% less in kidney. Concentration of thyroxine was 68% lower in kidney of selenium-deficient animals, and levels of 3,3',5-triiodothyronine in kidney and plasma were 44 and 31% lower, respectively. Thus, with the exception of thyroxine concentrations, thyroid hormone metabolism responds to selenium deficiency in guinea pigs as it does in rats, although the magnitude of that response is not as great. PMID- 7861258 TI - International Conference on Women's Health: Occupation and Cancer. Proceedings. Baltimore, Maryland, November 1993. PMID- 7861259 TI - Danish Cancer Registry as a resource for occupational research. AB - With its long tradition of population registration, Denmark has outstanding possibilities for occupational health research. The municipality registers date back to 1924, the national death and cancer registers to 1943, and unique personal identification numbers were introduced in 1968. For studies on occupational cancer, the cancer register has been linked with census data, pension data, and personnel files from various companies. Suspected associations between occupational exposures and cancer have been studied. For example, women in dry cleaning exposed to tetrachloroethylene had an excess risk of liver cancer (observed = 14; expected = 5.2; standardized incidence ratio (SIR) = 2.7; 95% CI = 1.5-4.5), and oncology nurses handling antineoplastic drugs had an excess risk of leukemia (SIR = 10.7), based on two cases. The linked registers have also been used to systematically search for associations between occupations and cancer risks (eg, female hairdressers). Cancer patterns differ greatly across countries and across main occupational groups within countries. Future efforts should focus not only on traditional approaches to occupational cancer research but also incorporate indirect influences of the work environment (eg, smoking, parity, age at first birth) and labor market participation on cancer risk. PMID- 7861260 TI - Utility of a surveillance system to detect associations between work and cancer among women in Canada, 1965-1991. AB - Data on the occupation and industry in which 242,196 females worked in Canada between 1965 and 1971 are available from a national survey of employers by Statistics Canada. As an example of the future utility of this cohort, computerized record linkage was conducted with the Canadian National Mortality Data Base through 1979. This article presents selected results. Associations are measured by standardized relative risks. Those meeting specific criteria (two or more observed deaths, relative risk > 2.0, and 95% confidence interval excluding 1.00) include (a) buccal cavity and pharyngeal cancer among mechanics and repairers, tobacco preparers and product makers, and telephone systems industry workers; (b) lung cancer among service station attendants, motor vehicle mechanics, and petroleum refinery workers; and (c) breast cancer among workers manufacturing electrical industrial equipment and printing and publishing industry workers. The mortality experience of the cohort through 1991 is currently being determined by another record linkage, thus providing up to 25 years of follow-up and over 8,500 cancer deaths anticipated among females. PMID- 7861261 TI - Studying cancer among female workers: methods and preliminary results from a record-linkage system in Italy. AB - In the context of a national program for occupational health surveillance, we examined cancer mortality among women from two study populations. The Torino Longitudinal Study includes 159,039 women, resident in Torino, northern Italy, 18 to 64 years old and economically active at the 1981 census. The Italian Cross sectional Study includes 2,038 deaths among 6,073,071 Italian women, 18 to 64 years old and economically active at the 1981 census. Preliminary results indicate that women in higher socioeconomic classes showed excess overall cancer mortality. This excess was almost entirely explained by increased breast cancer among teachers, managers, and public officials. Metal, wood, and clothing manual workers showed a significantly increased risk of ovarian cancer. Some excesses of lung and digestive cancers were noticeable among women in the textile and clothing industry and in the restaurant, bar, and hotel trade. Further study is under way. PMID- 7861262 TI - Occupation and hematopoietic and lymphoproliferative malignancies among women: a linked registry study. AB - Using a nationwide linked registry, we evaluated the incidence of several hematopoietic and lymphoproliferative (HLP) malignancies among Swedish women from 1961 to 1979 by industry and occupation. The risks of one or more types of HLP cancers (including the leukemias, non-Hodgkin's lymphoma, multiple myeloma, and mycosis fungoides) were significantly increased among women working in the agriculture and textile industries, housekeepers, and post office employees. Limitations of these linked-registry data include lack of detailed information on specific exposures and duration of employment, and the relatively small sizes of specific occupational cohorts. Nevertheless, as the proportion of women entering the workforce continues to increase, this data resource may provide additional clues to occupational determinants of HLP and other malignancies. PMID- 7861263 TI - Using occupational mortality data for surveillance of work-related diseases of women. AB - A recently developed source of occupational mortality data from 28 states for the years 1979 through 1990 can be used to meet goals for the surveillance of women's work-related diseases. A proportionate cancer mortality ratio analysis is used to illustrate use of the data to address the goals of identifying previously unrecognized work-related disease and targeting consultation or health promotion programs to appropriate occupations. Strengths of the data include broad geographical coverage and coverage of all causes of death and numerous industries and occupations. The data set is current and very large, with annual additions. The data have certain limitations. Death certificate information collected regarding occupation and cause of death may not be accurate; furthermore, death certificates have little information on potential confounding factors, such as smoking. PMID- 7861264 TI - Occupational cancer mortality among women employed in the telephone industry. AB - We conducted a mortality odds ratio (MOR) analysis among women employed in the telephone industry, using death certificates from 24 reporting states for 1984 through 1989. Usual occupation and industry from the death certificates were coded using the 1980 Bureau of the Census occupational and industrial classification system. There were 2444 cancer deaths among women in the telephone industry (code 441). Among younger (age < 49) white women, significant excess risks were observed from cancers of the rectum (MOR = 3.3; 95% confidence interval [CI] = 1.2 to 8.7), connective tissue (MOR = 4.4; 95% CI = 2.2 to 8.8), breast (MOR = 1.6; 95% CI = 1.3 to 2.1), corpus uteri (MOR = 3.3; 95% CI = 1.5 to 7.5), ovary (MOR = 2.1; 95% CI = 1.3 to 3.5), and brain (MOR = 2.1; 95% CI = 1.2 to 3.7). Cancer of the connective tissue showed an almost sixfold risk (MOR = 5.5; 95% CI = 2.0 to 14.8) for the age group of 30 to 39 years. Excess risks of cancer of the connective tissue were observed among engineers and technicians, office workers, telephone operators, and mechanics and repairers (MOR = 8.5, 4.9, 1.7, and 4.4, respectively), suggesting a possible relationship with modern technological exposures in the telephone industry. Risks for cancers of the breast, corpus uteri, ovary, and brain were also elevated among these jobs. We did not have information on other risk factors for these cancer sites; therefore, socioeconomic status or lifestyle may explain these observed associations, particularly for the cancers of the reproductive system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861265 TI - Risk of multiple myeloma by occupation and industry among men and women: a 24 state death certificate study. AB - This cancer surveillance investigation uses death certificates from 24 states for the period 1984-1989 to identify multiple myeloma and occupation associations and to stimulate hypotheses. A case-control study of multiple myeloma was created from 3,159,417 certificates in which 12,148 male and female cases were frequency matched by age, race, and gender with five controls per case. We screened 231 industries and 509 occupations. Women demonstrated significant excess risk among managers and administrators, post-secondary teachers, elementary teachers, social workers, other sales workers, waitresses, and hospital maids. Men showed significant risks among computer system scientists, veterinarians, elementary teachers, authors, engineering technicians, general office supervisors, insurance adjusters, barbers, electronic repairers, supervisors of extracting industries, production supervisors, photoengravers, and grader/dozer operators. Men and women elementary school teachers demonstrated the most consistent, statistically significant increased risk of multiple myeloma. PMID- 7861266 TI - Mortality from gastric cardia and lower esophagus cancer and occupation. AB - The incidence of adenocarcinoma of the gastric cardia and esophagus is increasing steadily in the United States. Little is known about the etiology of these cancers. We used occupation and industry information on the death certificates from 24 states (1984 to 1989) to conduct a case-control analysis of gastric cardia and gastric cardia/lower esophagus cancer. Risks were also calculated for other gastric cancers combined. Controls were deaths from other causes except cancer and gastrointestinal disorders. Increased risks of gastric cardia and cardia/lower esophagus among white women were found for administrative jobs (cardia odds ratio (OR) = 3.9; 95% confidence interval (CI), 1.5-9.8) and health professionals (cardia OR = 1.8; 95% CI, 0.6-5.3). Occupations associated with a lower socioeconomic status showed no significant excess risks. A similar pattern in risks was seen for men. PMID- 7861267 TI - Mortality patterns of US female construction workers by race, 1979-1990. AB - In 1990, the US construction industry employed 7.6 million workers, of whom 8% were women. Only one epidemiologic study for women employed in the construction industry was previously published. We analyzed usual occupation and industry codes on death certificates from 28 states between 1979 and 1990 to evaluate mortality patterns among both black and white female construction industry workers. Proportionate mortality for cancer and several other chronic diseases was significantly elevated among 2,273 white female and 197 black female construction workers. White women younger than age 65 at death had significantly elevated proportionate mortality ratios (PMRs) for all cancer, lung cancer, and traumatic fatalities. Black women younger than age 65 at death had a significantly elevated PMR for traumatic fatalities. Elevated mortality for specific cancer sites and other diseases was observed for white and black women employed in construction trades. These results suggest that more detailed investigations that include women and other minorities should be undertaken. PMID- 7861268 TI - Occupation and lung cancer mortality among women: using occupation to target smoking cessation programs for women. AB - Lung cancer mortality rates are increasing for women, despite the fact that 90% of these deaths could be prevented by smoking cessation. Targeted workplace smoking cessation programs may increase the effectiveness of lung cancer prevention for women. This study uses proportionate mortality ratio analysis of occupationally coded death certificates, from 28 states between 1979 and 1990, to identify occupations in which women are at high risk of lung cancer mortality. The study found gender and racial variation in the results for broad occupational groups. Blue-collar occupations associated with potentially carcinogenic workplace exposures also had elevated proportionate mortality ratios, probably reflecting both occupational and tobacco exposure. For women, specific occupations such as managers and financial officers revealed significant elevations in lung cancer mortality. Cessation programs targeting women in these occupational groups may increase the effectiveness of lung cancer prevention. PMID- 7861269 TI - Women at work: agriculture and pesticides. AB - Numerous occupational studies of cancer risks related to agriculture, agricultural practices, and agricultural exposures have been conducted among male farmers and farmworkers. Relatively few studies of female farmers and farmworkers have been conducted. Excesses of non-Hodgkin's lymphoma, leukemia, multiple myeloma, soft tissue sarcoma, and cancers of the breast, ovary, lung, bladder, cervix, and sinonasal cavities have been observed in women in agriculture or with agricultural exposures. Agents that contribute to ill health in exposed men may also affect exposed women, sometimes in unexpected ways. PMID- 7861270 TI - Cancer mortality among women employed in motor vehicle manufacturing. AB - This article summarizes published data on employment and cancer patterns in the motor vehicle manufacturing (MVM) industry and presents results from a new study of female MVM workers. Historically, female MVM employees worked primarily in aerospace; electric and electronic equipment manufacturing; and paint, plastic, and trim operations. Women are now moving into vehicle assembly and metal parts production. Investigations of cancer have focused on men and reported excesses of lung cancer in foundry operations, of gastrointestinal cancer in metal processing operations involving exposure to machining fluids, and of colorectal cancer in wood pattern making. Numbers of women were insufficient for a meaningful evaluation of their cancer patterns. A recent study found that white women employed at a MVM company, compared to the female general US population, had small excesses of lung cancer (standardized mortality ratio (SMR) = 1.26; 95% confidence interval (CI) = 0.96-1.63) and of colorectal cancer (SMR = 1.27, 95% CI = 0.87-1.78) and a deficit of breast cancer (SMR = 0.68, 95% CI = 0.48-0.92). The lung cancer increase was concentrated among women in assembly jobs (SMR = 1.58, 95% CI = 1.07-2.26); the colorectal cancer increase, among women in nonproduction jobs (SMR = 1.78, 95% CI = 0.97-2.98); and the breast cancer deficit, among women in production-related jobs (SMR = 0.60, 95% CI = 0.37-0.91). Further investigation is needed to determine if these patterns are due to the occupational environment and to clarify causes of cancer among women in the MVM industry. PMID- 7861271 TI - A cohort study of workers compensated for mercury intoxication following employment in the fur hat industry. AB - This article presents the preliminary results of a follow-up study (1950-1992) of 1,146 subjects (person-years = 30,954; 23,055 for women) receiving compensation for mercury poisoning. In a province of Tuscany in central Italy, severe exposure to mercury occurred during fur hat production. A deficit in all causes of mortality was observed in both sexes, whereas mortality due to cancer was slightly higher than expected. Mortality from stomach cancer was significantly elevated for men and women. A significant excess of lung cancer was observed in women only. Whereas the excess of stomach cancer probably reflects elevated rates in the study area rather than exposure to mercury, the excess of lung cancer mortality does appear to be related to mercury exposure. Smoking habits or other exposures at work do not seem to explain the excess of lung cancer. PMID- 7861272 TI - TMJ articular disc position and configuration 30 years after initial diagnosis of internal derangement. AB - PURPOSE: This study evaluates disc position and configuration on magnetic resonance imaging (MRI) in temporomandibular joints (TMJs) with a long history of internal derangement. PATIENTS AND METHODS: Sagittal T1-weighted MRIs of 55 TMJs that were diagnosed with internal derangement approximately 30 years ago were made with the mouth closed and open, and the position and configuration of the articular disc were determined. For comparison, a control group consisting of 15 asymptomatic TMJs without clinical signs of internal derangement or of other TMJ disorders were studied in the same way. RESULTS: Anterior disc position was found in 90% of the TMJs with a history of internal derangement. Reducing disc displacement was found in one third of these TMJs, whereas permanent displacement was found in two thirds. In four joints, no disc was discernible. In one of the joints of the control group, a permanent disc displacement was found; normal disc position was found in all other joints of the control group. A biconcave disc configuration, which was considered normal, was found only in TMJs with normal disc position or with reducing discs. CONCLUSION: It was concluded that, after 30 years of displacement, the TMJ disc can be clearly identified on MRI in most cases. If the disc becomes permanently displaced, its configuration deviates from the normal biconcave configuration, and its anteroposterior length decreases. Convex and folded appearances of the disc are common in this situation. However, the disc usually maintains its biconcave configuration as long as it resumes its position on top of the condyle during mouth opening, even if this condition lasts for several decades. PMID- 7861273 TI - Stability of Le Fort I osteotomy with maxillary advancement: a comparison of combined wire fixation and rigid fixation. AB - PURPOSE: This study compares two types of fixation: intraosseous wires, skeletal suspension wiring, and maxillomandibular fixation (combined wire fixation; CWF) with rigid internal fixation (RIF) in patients who underwent Le Fort I osteotomy to correct maxillary hypoplasia. MATERIALS AND METHODS: All patients were operated on by the same surgeon using a standard technique, which included bone grafting. The 12 patients in group A were treated with CWF for 4 weeks. Group B was made up of 13 patients who had RIF and training elastics for 4 weeks. Cephalometric analysis using a commercial software package was performed on radiographs that were taken immediately preoperatively (T1), 1 day postoperatively (T2), and at least 1 year postoperatively (T4). The position of the maxilla in relation to the cranial base and Frankfort plane at each time interval was compared. RESULTS: Postsurgical horizontal change (maxillary position change from T2 to T4) for both groups was in the posterior direction. In group A, six patients had less than 1 mm change, three had 1 to 2 mm change, and three had > 2 mm change. In group B, 10 patients had less than 1 mm change, three had 1 to 2 mm change and 0 had > 2 mm change. Comparison of mean values of groups A and B suggested improved stability with rigid versus wire fixation in the horizontal plane; however, statistical analysis of adjusted mean values showed no significant difference. Vertical changes in maxillary position were also measured from postoperatively to 1 year (T2 to T4). The vertical changes were minimal in those cases of maxillary advancement where no vertical changes were planned; however, there was a statistically significant (P = .0024) improved stability with RIF versus combined wire fixation cases. Comparison of adjusted means showed double the amount of vertical setting 1 year postoperatively in the CWF group. CONCLUSION: Overall, 22 of 25 patients with horizontal maxillary advancement had excellent stability at 1 year. Observed trends suggest that RIF may have improved stability over CWF. PMID- 7861274 TI - Hyperplasia of the mandibular coronoid process: an analysis of 31 cases and a review of the literature. AB - PURPOSE: This study was undertaken to investigate the demographic and clinical features of mandibular coronoid hyperplasia and to assess the response to current treatments. PATIENTS AND METHOD: Case notes were studied and records made of age, sex, duration of symptoms, operative procedures, and response to treatment in all patients presenting at the Queen Victoria Hospital, East Grinstead, over a 20 year period from 1970 to 1990 with a confirmed diagnosis of mandibular coronoid hyperplasia. RESULTS: Thirty-one cases were recorded, 23 bilateral and 8 unilateral. The average age on presentation was 27.8 years for bilateral and 23.6 years for unilateral cases, with symptoms predating presentation by an average of 9 years and 6.75 years, respectively. Surgery was disappointing in terms of improving mouth opening. CONCLUSION: The results of this large series are supported by meta-analysis of the previous literature. They suggest that surgical management may be improved by a greater understanding of the pathogenesis of this condition. PMID- 7861275 TI - Temporomandibular joint injury potential imposed by the low-velocity extension flexion maneuver. AB - PURPOSE: It has been proposed that significant temporomandibular joint injury can occur as a result of rapid extension-flexion motion of the neck (whip-lash). This motion, which is experienced by passengers in vehicles that undergo rear-end collisions, has been described as causing rapid protrusion and opening of the mandible. It has been speculated that this relative motion between the mandible and the cranium produces forces at the temporomandibular joint (TMJ) that injure the articular elements. The objective of this study was to measure these forces by an experimental method. MATERIALS AND METHODS: Accelerometer sensor and high speed cinematographic data were obtained from the kinematic responses of live human test subjects positioned as occupants in motor vehicles that underwent staged low-velocity rear-end collisions. Linear and moment forces generated at the TMJs were obtained from the resultant acceleration pulse at the craniomandibular complex, estimation of the mass properties of the mandible and its appended soft tissues, and the application of Newton's Second Law of motion. RESULTS: The maximum linear forces generated at the TMJ in a rear-end collision resulting in a velocity change of the test subject of 8 km/h (5 mph) were in the 7 to 10 N (1.6 to 2.2 lb) range. Moment forces at the joint peaked briefly at 0.55 N.m (4.81 lb-in). CONCLUSIONS: These force magnitudes generated at the TMJ constitute a minor fraction of the forces experienced at the joint during normal physiologic function. It is a conclusion of this study that injuries to the TMJ attributed to low-velocity "whiplash" cannot be accounted for by the joint forces produced by this maneuver. PMID- 7861276 TI - Implant survival rates in partially edentulous patients: a 3-year prospective multicenter study. AB - PURPOSE: This multicenter investigation is an interim 3-year survival report of a 5-year prospective study using Branemark osseointegrated implants in partially edentulous patients. MATERIALS AND METHODS: Previously defined patient characteristics and clinical parameters were related to implant survival using lifetable analysis. RESULTS: Three years after prosthesis insertion, 460 implants placed in 139 patients remained in the study. Cumulative success rates for maxillary implants (92.5%) were less than for mandibular implants (94.8%), with an overall cumulative success rate of 93.9%. CONCLUSION: Failures were associated with poor bone quality, smaller implant sizes, and a higher plaque index, and were more likely to occur before loading. A 4% incidence of residual long-term inferior alveolar nerve paresthesia was higher than previously reported. PMID- 7861277 TI - Evaluating function of the inferior alveolar nerve with repeated nerve conduction tests during mandibular sagittal split osteotomy. AB - PURPOSE: This article evaluates a new intraoperative recording technique for measuring the sensory nerve conduction velocity (SNCV) of the human inferior alveolar nerve (IAN) during orthognathic surgery of the mandible to assess the effects of intraoperative strain on function of the IAN. MATERIALS AND METHODS: The new test was successfully applied in 10 patients during bilateral sagittal split osteotomy of the mandible (20 IANs). The recordings were made with active wire electrodes at foramen ovale and stimulation was done at the mental foramen with two monopolar needle electrodes. The sensory nerve action potentials (SNAP) were recorded intraoperatively at three stages: 1) before the split, 2) after splitting of the mandible and possible mobilization of the IAN from the proximal bone fragment, and 3) at the end of the operation after fixation of the proximal and distal fragments with screws. RESULTS: The SNCV values (mean 64.1 m/sec) were obtained in all 20 nerves at stage 1, with no significant differences between the sides in latency or amplitude of the SNAPs. The sNAPs remained stable in the IANs not exposed during the operation. In the remaining nerves, the most obvious and statistically significant changes indicating nerve injury occurred between stages and 1 and 2. Partial transsection and mobilization of the IAN were equally potent in bringing about abnormal results in objective neurophysiologic tests as well as subjective sensory disturbances. The results of the intraoperative SNCV recordings correlated well with the findings of the mental nerve blink reflex tests conducted 2 weeks after the operation, whereas comparison of the results of clinical neurosensory testing with the intraoperative events and SNCVs were more inconsistent. CONCLUSIONS: Recording of the SNCV offers a useful objective tool for the examination of the IAN both intraoperatively and in clinical diagnosis. PMID- 7861278 TI - A comparison of three methods used for treatment of ranula. AB - PURPOSE: This report compares the treatment results for oral and plunging ranulas. PATIENTS AND METHODS: Twenty-seven patients were retrospectively examined concerning treatment methods and recurrence on the basis of their medical records. The surgical specimens were also examined microscopically. RESULTS: Four patients had excision of the ranula only, 22 had marsupialization, and nine had removal of the sublingual gland combined with the excision of the ranula. These treatments showed a 25.0%, 36.4% and 0% recurrence rate, respectively. Histological observation revealed no epithelial lining in any of the examined specimens. CONCLUSIONS: Removal of the sublingual gland combined with the ranula was the most reliable method among the above three used. PMID- 7861279 TI - A comparison of the bond strengths of two different dentine-bonding agents to bone. AB - PURPOSE: This study was performed to test the bond strength obtained between composite and bone using two different dentine-bonding agents. MATERIALS AND METHODS: P50 composite was bonded to 60 specimens of pig calvarium using All bond 2 (Bisco, Itaska, IL) or A.R.T. bond (Coltene, Altstatten, Switzerland) dentine bonding agents. The bonds were tested to failure in an Instron Universal Testing machine (High Wycombe, UK) and the bond strength calculated. Data were analysed using the Weibull distribution. RESULTS: All-bond 2 and A.R.T. bond produced mean bond strengths of 8.5 MPa and 8.4 MPa, respectively, in the model used. The Weibull moduli were 2.4 and 2.1, respectively. CONCLUSIONS: There was no significant difference in the performance of the adhesives tested when used to bond composite to bone. The bond strengths obtained give rise to some optimism over the possible use of these systems in bone fracture fixation. PMID- 7861280 TI - Evaluation of horizontal and vertical tracheotomy healing after short-duration tracheostomy in dogs. AB - PURPOSE: The purpose of the study was to assess healing of horizontal and vertical tracheotomy after short-duration tracheostomy in dogs using clinical, radiographic, endoscopic, and histologic methods. MATERIALS AND METHODS: Horizontal tracheotomy (n = 6) between the third and fourth tracheal rings or vertical tracheotomy (n = 6) across tracheal rings three through five was performed for airway management during laryngoplasty. Tracheostomy tubes were maintained for 6 hours with low-pressure cuff inflation time limited to the first 1.5 hours. Cervical radiographs and tracheoscopy were performed preoperatively and at postoperative weeks 2, 4, 8, and 12. Ten of the 12 dogs were killed 12 weeks after tracheostomy. RESULTS: There was no significant difference in preoperative and postoperative tracheal diameter or change in endoscopic tracheal circumference at the tracheostomy site when dogs were compared based on type of tracheotomy. Three dogs with horizontal tracheotomies had evidence of scar (web) within the tracheal lumen 12 weeks after surgery. All vertical tracheotomies had a mild, ventral, triangular deformity. Histologic examination of vertical tracheotomy sites showed complete restoration of the pseudostratified columnar epithelium. Horizontal tracheotomies healed with a single layer of columnar epithelium. Intraluminal scar was composed primarily of loose connective tissue. CONCLUSION: Based on the results of this study, vertical tracheotomy shows more consistent healing compared with horizontal tracheotomy after short-duration tracheostomy. No evidence was found to support the preferential recommendation of horizontal tracheotomy for short-duration tracheostomy airway management. PMID- 7861281 TI - Reconstruction of the severely atrophic edentulous mandible with the transmandibular implant system. PMID- 7861282 TI - Reconstruction of the severely atrophic edentulous mandible with endosseous implants: a 10-year longitudinal study. PMID- 7861283 TI - Eye injury during general anesthesia for oral and maxillofacial surgery: etiology and prevention. PMID- 7861284 TI - Epidermoid cyst in a temporomandibular joint dermal graft: report of a case and review of the literature. PMID- 7861285 TI - Oromandibular dystonia treated with botulinum toxin: report of case. PMID- 7861286 TI - Traumatic submandibular salivary gland fistula. PMID- 7861287 TI - Improvement of a condylar positioning system for the mandibular ramus sagittal split osteotomy. PMID- 7861288 TI - Use of a modified epidural catheter for analgesia after iliac crest bone procurement. PMID- 7861289 TI - The correct operation for TMJ disc perforation. PMID- 7861290 TI - [Clinical evaluation of asymptomatic sinus disease detected by MRI]. AB - The detection of lesions of the paranasal sinuses as incidental findings during magnetic resonance imaging of patients suspected of intracranial disease who have no nasal symptoms has been far more common than we expected. The present study was performed on 325 patients a mean age of 60.7 years. Medical histories were taken whether they had any nasal symptoms or not. Asymptomatic sinus disease was present in 41.6% of the 257 patients who had no nasal symptoms, and 9.7% of the patients had either marked mucosal thickening, excessive fluid or polyps in the maxillary sinuses. Although the mean age of these patients was comparatively high, we can infer that 1 in 10 have relatively severe sinus lesions. Mucociliary transport time was measured using the saccharin method in 15 patients who had sinus disease but no nasal symptoms. The mean transport time was 15.6 minutes and within normal limits. Routine ENT examination revealed no lesions in the nasal cavity of any of the subjects. We classified the patients with asymptomatic sinus disease into two groups; group A: patients with sinus disease associated with some nasal manifestations but who do not complain about them, group B: patients who have sinus disease but do not have any nasal problems. Group B represents genuine asymptomatic sinus disease in the narrow sense. Most asymptomatic patients in this study appeared to belong to group B. They had some sinus disease, but because their mucociliary function in their nasal cavity was normal, they did not have any nasal symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861291 TI - [Undifferentiated carcinoma of cervical node metastases in patients with an unknown primary lesion: an immunohistochemical study]. AB - Sixteen patients with lymphatic metastases to the neck and a histological diagnosis of undifferentiated carcinoma from an unknown primary lesion were assessed using immunohistochemical staining. The results revealed a non epithelial tumor in 11 cases (malignant lymphoma in 5 cases) and an epithelial tumor in 3 cases. The patients with malignant lymphoma had a good outcome, but those with other non-epithelial tumors did not. Treatment of patients with an unknown primary tumor, especially undifferentiated carcinoma, should be carefully evaluated based on immunohistological examinations to identify malignant lymphoma. PMID- 7861292 TI - [Longitudinal studies in hearing-impaired children with Down's syndrome]. AB - Over the past twenty years hearing impairment has become widely recognized as one of the most important problems in the children with Down's syndrome. We have continued longitudinal observations of the hearing and speech development of children with Down's syndrome during the 10-year period from 1982 to 1991. One hundred ten children with Down's syndrome were examined and followed in the Department of Otolaryngology, Teikyo University Hospital. The examinations included otomicroscopy, behavioral audiometry, auditory brain stem response audiometry and tympanometry. Questionnaires were also administered to obtain information on the speech and hearing development of the children. In the present paper, we discuss assessment of hearing evaluation and the characteristics (degree, incidence, and types) of hearing impairment in Down's children. We divided the children into the following groups according to hearing acuities: 35 children with a normal hearing level (0-39 dB), 54 children with a moderately impaired hearing level (40-79 dB) and 21 children with a hearing level above 80 dB, and in 12 of these 21 children the finding was unilateral, and the 9 remaining children was bilateral. Thus the incidence of hearing impairment with a threshold higher than 40 dB was 68%. We detected otitis media with effusion (OME) in 34 (63%) of the 54 children with moderate hearing loss. Active treatment with medication or minor surgery, such as myringotomy or insertion of a ventilation tube, resulted in remarkable improvement in hearing in 26 children with OME. We used hearing aids for patients with prolonged otitis media and those with a hearing loss greater than 50 dB in both ears. When their hearing acuity improved in response to appropriate medical care and the use of hearing aids, human relations improved and speech development accelerated. We emphasize that appropriate medical care and management of hearing impairment, including the use of hearing aids, were required for both patients' emotional and linguistic development. PMID- 7861293 TI - [Ultrastructural characteristics of mast cells and eosinophils in nasal inverted papilloma]. AB - We previously found that an increased number of mast cells and eosinophils accumulated in nasal inverted papilloma and in the nasal mucosa of allergic subjects. Two subtypes of mast cells, i.e., mucosal mast cells and connective tissue mast cells are known to be present in the allergic nasal mucosa. Eosinophils in the allergic nasal mucosa are also heterogeneous. In addition, we demonstrated accumulation of formalin-sensitive mast cells at the tumor site of nasal inverted papilloma. The morphological characteristics and function of mast cells and eosinophils, however, have not yet been identified. The purpose of this study was to determine the ultrastructural characteristics of mast cells and eosinophils in relation to their function in tumor tissue. The results revealed two subtypes of mast cells in nasal inverted papilloma, one distributed mainly in the tumor site, the other mainly in the stromal site. These two subtypes of mast cells had different ultrastructural characteristics. In contrast to stromal mast cells, mast cells in the tumor site were characterized by a smaller cell diameter, fewer specific granules and a higher rate of degranulation. This suggested that they may have played some role in the pathogenesis of the tumor, however, their precise function is still unknown. In comparison with the mast cells in the allergic nasal mucosa, previously reported by Okuda et al, the mast cells in the tumor site were similar to those in the epithelial layer of the allergic nasal mucosa (MMCs), while mast cells in the stromal site resembled those in the lamina propria (CTMCs). There were no marked morphological differences between eosinophils in the tumor site and the stromal site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861294 TI - [Recording characteristics of the eye mark recorder in measurements of vertical eye movements]. AB - Electronystagmography (ENG) has been widely used in physiological studies of eye movements. It is generally known that ENG is at a disadvantage in recording the vertical component of eye movements, and thus there has been a great deal of difficulty in physiological studies of vertical eye movements using ENG. The eye mark recorder is an instrument which has already been used in the study of visual point movement in various situations. We tried to apply the eye mark recorder to the recording of eye movements in normal volunteers, and then compared its recording characteristics with those of ENG. When recording vertical eye movements with the eye mark recorder there is little baseline drift and no confusing waves caused by blinking, which is sometimes misinterpreted as nystagmus. The result is easy calibration of the device and more accurate measurement of the slow-phase velocity of nystagmus than ENG. Recording with the eye mark recorder is atraumatic and allows binocular visual stimulation. There are certain other techniques, such as search coil or video oculography, which allow more accurate recording of vertical eye movements than ENG. The search coil techniques, however, requires the attachment of a measuring contact lens during the examination and video oculography is still in development process, so both of them are difficult to use widely. Thus, we found that the eye mark recorder has a great advantage in recording the slow-phase eye velocity of vertical nystagmus and the vertical component of smooth eye movements in humans. We think that eye mark recorder can serve as a powerful new tool to investigate vertical OKN and OKAN. PMID- 7861295 TI - [3D-CT of the temporal bone area with high-speed processing]. AB - Three-dimentional (3D)-CT was introduced to represent abnormal findings in the temporal bone area utilizing a SOMATOM DRH CT scanner with accessory 3D reconstruction software and an exclusive high-speed 3D processing system, VOXEL FLINGER. In a patient with eosinophilic granuloma, a defect in the squamous part of the temporal bone was demonstrated suggesting exposure of the dura mater during surgery. In a patient with a normal ear, well-developed mastoid cavity, a part of the handle and the head of the malleus, the incudomalleal joint, the short limb, body and a part of the long limb of the incus and the round window niche were demonstrated. In a case of chronic otitis media, poorly developed mastoid cavity and a possible defect of the tip of the long limb of the incus were demonstrated, in contrast to the patient with the normal ear. 3D-CT yields objective and solid images which are useful for diagnosis, treatment planning and explanation of the pathology to patients and their family. To obtain convincing 3D images, physicians themselves have to choose exact rotation angles. It is not adequate to reconstruct original CT data using a CT computer with accessory 3D software whose processing capability is not good enough for this purpose. The conclusion is as follows: 1) it is necessary and effective to transfer original CT data into the memory of the exclusive high-speed 3D processing system and 2) process the data by the voxel memory method to establish a clinically valuable 3D CT imaging system. PMID- 7861296 TI - [Evaluation of the method of treating non-Hodgkin's lymphoma]. AB - Forty-two patients with non-Hodgkin's lymphoma were treated between October 1983 and December 1992 in the department of Otolaryngology, Kagawa Medical School Hospital. The twenty-six of these patients whose tumor originated in Waldeyer's ring and who were diagnosed as Stage I or II have been reviewed. In principle, method of treatment was a combination of chemotherapy and radiotherapy. Between 1983 to 1987, COP was primarily used (9 cases) as combination chemotherapy, and after 1988 CHOP was used (17 cases). VAMA was used to treat the poor response and recurring cases. The five-year estimated overall survival rates calculated by the Kaplan-Meier method were 33.3% and 94.1% in the COP and CHOP groups, respectively. We investigated age, stage, cell type and grade, as factors related to recovery, but except for cell type, there were no significant differences in overall survival. The most serious side effect was decreased leucocyte count, but we prescribed G-CSF and were able to continue treatment. PMID- 7861297 TI - [Flow cytometric DNA analysis and chemosensitivity in squamous cell carcinoma of the head and neck]. AB - Cellular DNA content and succinate dehydrogenase activity of 92 human head and neck (34 laryngeal, 24 pharyngeal, 21 oral cavity, 13 maxillary) squamous cell carcinomas were examined, and DNA ploidy status and chemosensitivity were analyzed and compared. DNA aneuploidy was observed in 54 tumors (58.7%). The aneuploid pattern was most common in tumors of the maxillary sinus (84%), and least common in tumors of the larynx (41.3%). Histologically, aneuploidy was detected in 71.4% of poorly-differentiated, 63.8% of moderately-differentiated and 37.5% of well-differentiated squamous cell carcinomas. There was a statistically significant difference between the survival rates of patients with diploid and aneuploid patterns. Chemosensitivity was determined by exposing fresh tumor material to five antitumor drugs: adriamycin (ADM), cisplatin (CDDP), carboquone (CQ), 5-fluorouracil (5-FU) and mitomycin C (MMC). The average decrease in succinate dehydrogenase (SD) activity was 49.8% with ADM, 33.6% with CDDP, 39.9% with CQ, 68.4% with 5-FU and 45.5% with MMC. Histologically, poorly differentiated squamous cell carcinomas were most sensitive to these five antitumor drugs. We also compared average SD activity in tumors from different organs and found that pharyngeal tumors tend to be most sensitive to these drugs, except for MMC. The chemosensitivity of a tumor with DNA diploidy tended to be higher among well- and moderately-differentiated squamous cell carcinomas. In contrast, tumors with DNA aneuploidy tended to have higher chemosensitivity in the poorly-differentiated type. The results of this study indicate that simultaneous analysis of DNA ploidy and chemosensitivity will be helpful in understanding the characteristics of tumors as well as in predicting the most effective chemotherapy agents for head and neck cancer patients. PMID- 7861298 TI - [Superoxide production by neutrophils in patients with recurrent tonsillitis]. AB - Superoxide anion (O2-) production by peripheral blood polymorphonuclear leukocytes (PMNs) stimulated with phorbol myristate acetate (PMA) was measured by the cytochrome C method in 57 patients with recurrent tonsillitis. There was no significant correlation between superoxide production and episodes of acute tonsillitis, serum C-reactive protein levels, or peripheral white blood cell count. However, the superoxide production by PMNs was inversely correlated with serum anti-streptolysin-O titers (r = -.38, p = .008). Furthermore, the mean +/- SD superoxide levels produced by PMNs from patients with high serum ASO titers (> 71 U/ml), 69.58 +/- 30.56 nM/10(6) cells, was significantly lower than that of patients with low serum ASO titers (< 71 U/ml), 89.83 +/- 38.90 nM/10(6) cells (p = 0.037), and that of healthy adult controls, 102.27 +/- 44.67 nM/10(6) cells (p = 0.012). In addition, the effect of Streptococcus pyogenes on superoxide production by PMNs was studied in vitro. Superoxide production by PMNs preincubated with 600 micrograms/ml culture supernatant of Streptococcus pyogenes T4 (not detected) and T12 (34.82 +/- 31.40 nM/10(6) cells) was significantly lower than that of PMNs preincubated with culture medium (136.09 +/- 70.41 nM/10(6) cells; p < 0.05, each). Inhibition of superoxide production by PMNs by preincubation with culture supernatant of Streptococcus was increased by the protein in the culture supernatant in a concentration-dependent manner. These findings suggest that frequent and/or persistent streptococcal infections may reduce the superoxide production by PMNs, leading to recurrent episodes of tonsillitis. PMID- 7861299 TI - [A study on maximal permissible drug concentration for transnasal medication from the viewpoint of ciliary activity of the cultured human paranasal mucosa]. AB - Aerosol therapy has been widely used for upper and lower airway diseases. However, maximal permissible concentrations of drugs have not yet been clarified. The purpose of this study was to find the maximal drug concentration for transnasal medication that does not inhibit ciliary activity or tissue. Human paranasal sinus mucosa taken at surgery was cut into small pieces. These were cultured in RPMI-1640 medium under the conditions of 5% CO2 and 100% relative humidity at 37 degrees C. Histopathologic damage was observed under a microscope at 400 x magnification. The rate of ciliary beating was measured by a photoelectric method with a cadmium sulphite photometer. In order to compare the findings with those of repeated clinical nebulizer therapy, drug application once a day for 3 days and combined use with steroids were examined for 30 min, considering maximal retention time of the drugs in the nasal cavity as an aerosol therapy. The maximal permissible concentrations of several drugs in single use obtained by these experiments were as follows: acetylcysteine 4.4%, tyloxapol 0.03%, sodium cromoglycate 4%, Broncasma Berna 2 times, prednisolone 1%, dexamethasone 0.2%, betamethasone 0.4%, kanamycin 20%, gentamicine 1%, amikasine 4%, dibekasin 4%, astromysin 4%, fosfomycin 3%, clindamycin 3%, ampicillin 10%, cefazolin 5%, and lidocaine 0.01%. When antibiotics and ateroids were used at the same time, the ciliary activity and the tissue were damaged more strongly than with single use. Therefore, the maximal concentration of some drugs has to be reduced. For example, the maximal concentration of prednisolone, 1%, was reduced to 0.2%, and that of kanamycin, 20%, was changed to 10%. PMID- 7861300 TI - [p53 abnormality in salivary gland carcinoma and its relation to tumor DNA aneuploidy and AgNOR]. AB - Recent studies have shown that inactivation of tumor suppressor p53 gene is a key point in the development of human carcinomas and that normal p53 protein acts as a "molecular policeman" monitoring the integrity of the genome. In the present study, a series of 22 primary human salivary gland carcinomas were examined for alterations and expression of the p53 gene by a combined molecular and immunohistochemical approach, polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP), direct gene sequencing and p53 protein immunostaining. In addition, in order to identify correlations between p53 abnormalities and genetic instability, DNA aneuploidy and tumor growth characteristics were analyzed by cytofluorometry and the AgNOR technique. Seven of the 22 cases displayed nuclear p53 overexpression as revealed by immunostaining with p53 monoclonal antibody (Do-7), and 2 of these 7 cases were associated with the presence of point mutations [codon 140: ACC (Thr)-->ATC (Ile), codon 175: CGC (Arg)-->CAC (His)] of the p53 gene. Twelve of the 22 cases were aneuploid on the DNA histogram, and this phenomenon was statistically correlated with the 7 cases exhibiting p53 nuclear accumulation. AgNOR staining, on the other hand, was not statistically correlated with p53 abnormalities. These findings support the view that abnormal nuclear accumulation of the p53 protein is correlated with genetic instability of human salivary gland carcinoma cells. PMID- 7861301 TI - Introduction: social cognition, psychodynamic psychology, and the representation and processing of emotionally significant information. AB - This special issue examines two perspectives on how people comprehend and respond to significant features of their lives: psychoanalytic psychology and social cognition. The articles included present new empirical findings relevant to the overlap of psychoanalysis and social-cognitive psychology, as well as commentaries from each perspective. This introduction summarizes important conceptual and methodological challenges in the integration of two such distinct approaches to emotionally significant information. PMID- 7861302 TI - Transference in interpersonal relations: inferences and affect based on significant-other representations. AB - Based on an information-processing model of transference and a recent experimental demonstration of transference, defined in terms of "biased inference and memory" (Andersen & Cole, 1990), the present research examined the transfer of affective responses to a new individual, as in schema-triggered affect (Fiske, 1982). Using idiographic stimulus-generation procedures and a nomothetic experimental design, we exposed subjects to a description of a new, unknown person, allegedly seated next door. The description resembled either a positively or negatively toned significant other from the subject's own life or from another subject's life. As predicted, and replicating previous work, subjects misremembered the target person as having more representation-consistent features when the target resembled their own significant other rather than someone else's. Moreover, and also as predicted, subjects transferred more representation consistent affect to this same target person. The data are discussed in terms of conceptions of transference and basic aspects of social cognition. PMID- 7861303 TI - Consistency of interpersonal themes for patients in psychotherapy. AB - In this study the extent to which patients in psychotherapy display similar interpersonal themes across multiple narratives of their interactions with others was investigated. Interpersonal themes were measured using a new instrument entitled the Quantitative Assessment of Interpersonal Themes (QUAINT) method, which assesses the wishes, responses from others, and responses of self that occur in narratives about interactions with others. For 60 patients in psychotherapy, evidence for repetitiveness of themes was found; the effect was relatively small but was highly statistically significant. Individual differences in the degree of repetitiveness of themes were not related to type of treatment (dynamic vs. cognitive), but they were related to length of time in treatment. The limitations of the study are reviewed and future research directions are outlined. PMID- 7861304 TI - Expressive and defensive behavior during discourse on unresolved topics: a single case study of pathological grief. AB - Both psychodynamic and social-cognitive theoretical domains have control process models of behavior but with different ideas about the purpose and loci of control. This study examines expressive and defensive behaviors associated with different topics of discourse in the time-limited psychotherapy of a woman treated for pathological grief. Conceptually the study is based on a model of defensive control processes that integrates states of mind and person schemas. Theoretically derived measures of discourse topics, verbal and nonverbal defensive behaviors, emotional disclosure, and states of mind were applied to transcripts and videotapes of the entire therapy. Evidence from combined cluster and factor analyses supported the existence of recurring emotionally significant states. Two of these are particularly interesting from a clinical perspective: One, a "shimmering" state of intense emotional expression with concurrent signs of avoidance, was associated with topics identified clinically as stressful, unresolved, and conflictual. The other, a state of more uniformly stifled emotionality, was characteristic of discourse thought of clinically as resistance. PMID- 7861305 TI - The body's response to processing emotional trauma: linking verbal text with autonomic activity. AB - When individuals talk or think about upsetting experiences, different coping and defensive processes are invoked from one minute to the next. Further, some coping strategies are thought to be more effortful and to be associated with greater biological activity than others. The present research sought to identify how the expression of emotions and the use of different psychological defenses were reflected in momentary changes in autonomic nervous system activity while subjects wrote about emotional topics. A new methodology is introduced that links the production of natural written language with autonomic activity on a word-by word or phrase-by-phrase basis. Using this technique with a sample of 24 subjects who wrote about traumatic experiences, it was found that certain text dimensions are highly related to skin conductance level (SCL) but not heart rate. In general, subjects' SCLs increased when expressing negative emotions and when using denial and the passive voice. SCLs were more likely to drop when subjects used positive emotion words and self-references and at the conclusion of sentences or thought units. Implications for this methodology for understanding psychological defense and physical health are discussed. PMID- 7861306 TI - Styles of inhibiting emotional expression: distinguishing repressive coping from impression management. AB - Although repressors' avoidant coping style seems genuinely defensive, an alternative hypothesis is that repressors are actually distress-prone impression managers who provide "socially desirable" verbal reports. To establish discriminant validity, 30 repressors and 30 self-identified impression managers participated in a timed phrase-completion task. Half of the subjects were encouraged to be emotionally expressive and half to be restrained. Repressors were highly defensive regardless of the social demand, and impression managers only managed to match the repressors' level of distancing during the first segment of the inhibitive condition. Repressors were as physiologically reactive when they made defensive claims as they were when they made more negative disclosures to others. Moreover, when confronted, only the repressors denied that their heart rate elevations might be related to their emotional responses. These findings suggest that repressors' limited emotional expression is more determined by defenses against awareness of affect than by self-presentational concerns. PMID- 7861307 TI - Chronic thought suppression. AB - We conducted several tests of the idea that an inclination toward thought suppression is associated with obsessive thinking and emotional reactivity. Initially, we developed a self-report measure of thought suppression through successive factor-analytic procedures and found that it exhibited acceptable internal consistency and temporal stability. This measure, the White Bear Suppression Inventory (WBSI), was found to correlate with measures of obsessional thinking and depressive and anxious affect, to predict signs of clinical obsession among individuals prone toward obsessional thinking, to predict depression among individuals motivated to dislike negative thoughts, and to predict failure of electrodermal responses to habituate among people having emotional thoughts. The WBSI was inversely correlated with repression as assessed by the Repression-Sensitization Scale, and so taps a trait that is quite unlike repression as traditionally conceived. PMID- 7861308 TI - Commentary: psychodynamics and social cognition--notes on the fusion of psychoanalysis and psychology. AB - Interest in linking psychoanalysis with scientific psychology waxes and wanes. In part, the difficulties have been caused by the preference of psychoanalysts for Freud's clinical theory (and its emphasis on narrative truth) as opposed to his metapsychology (with its requirement for historical truth). Even though contemporary scientific psychology evolved largely independently of psychoanalysis, the articles on object relations, transference, and defense published in this special issue show that the theory remains a source of inspiration, observations, and hypotheses. PMID- 7861309 TI - Linguistic intergroup bias: differential expectancies or in-group protection? AB - The linguistic intergroup bias describes the tendency to communicate positive in group and negative out-group behaviors more abstractly than negative in-group and positive out-group behaviors. This article investigated whether this bias is driven by differential expectancies or by in-group protective motives. In Experiment 1, northern and southern Italian participants (N = 151) described positive and negative behaviors of northern or southern protagonists that were either congruent or incongruent with stereotypic expectancies. Regardless of valence, expectancy-congruent behaviors were described more abstractly than incongruent ones. Experiment 2 (N = 40) showed that language is used in an equally biased fashion for individuals as previously demonstrated for groups. Experiment 3 (N = 192) induced expectancies experimentally and found greater abstraction for expectancy-congruent behaviors regardless of valence. All experiments confirmed the differential expectancy approach. PMID- 7861310 TI - Peripheral ingroup membership status and public negativity toward outgroups. AB - Peripheral membership status in a desirable ingroup was predicted to elevate outgroup derogation when Ss believed other ingroup members might learn of their responses. Less negativity toward outgroups was expected when peripheral members' responses were to remain private. Core ingroup members, in contrast, were not expected to show public-private differences in derogation of outgroups. The results of 2 experiments supported these predictions, with peripheral but not core ingroup members advocating the most coercion for the outgroup under public conditions in both laboratory-created ingroups (Experiment 1) and naturally occurring groups that had meaning for the participants (Experiment 2). Thus, outgroup derogation can serve a public presentation function that allows for enhancement of an insecure status within a desirable ingroup. PMID- 7861311 TI - Assessing psychopathic attributes in a noninstitutionalized population. AB - The present study examined antisocial dispositions in 487 university students. Primary and secondary psychopathy scales were developed to assess a protopsychopathic interpersonal philosophy. An antisocial action scale also was developed for purposes of validation. The primary, secondary, and antisocial action scales were correlated with each other and with boredom susceptibility and disinhibition but not with experience seeking and thrill and adventure seeking. Secondary psychopathy was associated with trait anxiety. Multiple regression analysis revealed that the strongest predictors of antisocial action were disinhibition, primary psychopathy, secondary psychopathy, and sex, whereas thrill and adventure seeking was a negative predictor. This argues against a singular behavioral inhibition system mediating both antisocial and risk-taking behavior. These findings are also consistent with the view that psychopathy is a continuous dimension. PMID- 7861312 TI - State and trait negative affect as predictors of objective and subjective symptoms of respiratory viral infections. AB - State and trait negative affect (NA) were measured in healthy people immediately before an illness was induced through exposure to a respiratory virus. State NA, disease-specific health complaints (e.g., runny nose, congestion, and sneezing), and an associated objective marker of disease severity (mucus secretion weights) were assessed daily during the illness. Baseline trait and state NA were both associated with increased numbers of subsequent complaints. Although greater numbers of complaints among people high in state NA were explicable in terms of greater disease severity, the association of trait NA and symptoms was independent of objective disease. The trait NA complaint association was also independent of state NA and hence not attributable to trait-elicited state affect. Greater trait NA was associated with biases in complaining during but not before illness. This suggested failure to discriminate between symptoms rather than increased sensitivity or hypochondriacal response. PMID- 7861313 TI - Knowing what you'll do: effects of analyzing reasons on self-prediction. AB - Analyzing the reasons why one would or would not act in a certain way was predicted to increase the perceived likelihood of the behavior and to lower the accuracy of the self-predictions. In 3 studies, college students predicted whether they would act in friendly or unfriendly ways toward an acquaintance. Those asked to analyze reasons why they would or would not perform the behaviors, as compared with no-analyze controls, were more likely to say they would perform the behaviors, showing a confirmation bias; made less accurate predictions, because analyzing reasons changed their predictions but not their actual behavior; and were more overconfident, because analyzing reasons lowered accuracy but not confidence. Each of these effects was especially pronounced when people's initial liking for the target person was different from the valence of the behavior they were predicting. PMID- 7861314 TI - Flexible correction processes in social judgment: the role of naive theories in corrections for perceived bias. AB - Unlike many models of bias correction, our flexible correction model posits that corrections occur when judges are motivated and able to adjust assessments of targets according to their naive theories of how the context affects judgments of the target(s). In the current research, people flexibly correct assessments of different targets within the same context according to the differing theories associated with the context-target pairs. In Study 1, shared theories of assimilation and contrast bias are identified. Corrections consistent with those theories are obtained in Studies 2 and 3. Study 4 shows that idiographic measures of theories of bias predict the direction and magnitude of corrections. Implications of this work for corrections of attributions and bias removal in general are discussed. PMID- 7861315 TI - Origins of attitude importance: self-interest, social identification, and value relevance. AB - Five studies examined the relations between attitude importance and 3 of its hypothesized determinants: self-interest, social identification with reference groups or reference individuals, and cherished values. Verbal protocols, multivariate analysis of survey data, and laboratory experimentation revealed that (1) people's theories of the causes of attitude importance pointed to all 3 hypothesized predictors, (2) the 3 predictors each had significant, unique statistical associations with importance, and (3) a manipulation of self-interest yielded a corresponding change in importance. These results help clarify the nature and origins of attitude importance, challenge the widely believed claim that self-interest has little or no impact on political cognition, and identify new likely consequences of social identification processes and values. PMID- 7861316 TI - Components and recognition of facial expression in the communication of emotion by actors. AB - This article addresses the issue of the communication of emotion by actors. In Study 1, the facial behavior of 6 actors portraying emotions as felt or unfelt were analyzed with the Facial Action Coding System. Results indicated that the portrayals of felt emotions were closer to the expression of genuine emotion than the portrayals of unfelt emotions for 3 of the 6 emotions under investigation. Study 2 examined the decoding of actors' portrayals from facial behavior. Decoders were found to be very accurate in recognizing the emotional category but not in judging the encoding condition. PMID- 7861317 TI - Subgroup differentiation and subgroup bias among Latinos as a function of familiarity and positive distinctiveness. AB - The existence of subgroup differentiation and its impact on the development of in group bias were explored among Latinos. Consistent with prior evidence, Cubans, Mexicans, and Puerto Ricans were more likely than Anglos to distinguish between Latino subgroups. However, Latinos did not distinguish equally between Cubans, Mexicans, and Puerto Ricans. Latinos differentiated their own subgroup from others but were no more likely than Anglos to differentiate between Latino subgroups to which they did not belong. Latinos even regarded the term Hispanic as more applicable to members of their own subgroup than to members of other subgroups. This tendency among Latinos to view their own subgroup as distinct from others was also linked to a bias for fellow subgroup members but not for Latinos overall. Moreover, results suggested that subgroup differentiation was based more on a desire for positive distinctiveness than on familiarity with members of different Latino subgroups. PMID- 7861318 TI - Distal skin plasty of the hallux for clubbing deformity after total nail loss. AB - The author provides a comprehensive review of clubbing deformity and its clinical manifestations after total nail procedures of the hallux. Conservative and surgical treatment is presented with a distal skin plasty procedure described in detail. PMID- 7861319 TI - Plantar incisional approaches. Current perspectives. AB - Plantar incisions on the feet have been a controversial subject for many years because of the potential untoward effects of scarring. The author presents a variety of techniques and the rationale for the use of plantar foot incisions, along with discussion on the prevention of complications. PMID- 7861320 TI - Wound closure and special suture techniques. AB - In this review, the author presents the physiologic events in wound healing. A discussion is provided with emphasis on proper tissue handling and suture techniques. A variety of methods are demonstrated as they are applied to specific clinical situations in foot and ankle surgery. It is the intent of this discussion to add information and techniques that may be used to complement general knowledge in wound and incision repair. PMID- 7861321 TI - V-Y plasty and its variants. AB - The authors present an overview of the V-Y plasty technique with a discussion of the basic underlying principles and a description of the surgical technique. The variations available and the direct application of this procedure are discussed with reference to the foot and ankle. Consideration is given for design, location, survival, and postoperative care of the V-Y plasty. PMID- 7861322 TI - Use of Z-skin plasty in scar revisions and skin contractures of the lower extremity. AB - A discussion of the design and use of the Z-skin plasty to revise scars and lengthen skin contractures of the lower extremities is presented. One of the most commonly used rotational flaps to alter scar direction or relieve tension on the existing scar or skin, the Z-plasty can also be the most difficult to perform and carries a high risk of flap loss if inaccurately planned or poorly placed. Several variations of the standard procedure and examples of common usage are presented. PMID- 7861323 TI - Single-lobe rotation flaps. AB - The basic principles of a single-lobe flap are discussed along with the description of a modified slide-swing rotational flap. This rotation flap is called the Schrudde flap, and it has many applications in the treatment of skin defects of the foot and ankle. This rotation skin flap procedure provides excellent end results with high patient acceptance. PMID- 7861324 TI - Unilobed and bilobed skin flaps. Detailed surgical technique for plantar lesions. AB - The authors provide a detailed description of effective surgical techniques for painful plantar skin lesions of the foot that are not amenable to simple excisional procedures. Modified unilobed and bilobed skin flaps are described, emphasizing step-by-step design and procedure performance. These advanced techniques offer numerous advantages over other excisional and flap methods, such as being reproducible and yielding predictable results. PMID- 7861325 TI - Use of skin grafting in the foot. AB - Skin grafting is a useful adjunct to treating open wounds. It not only provides rapid wound coverage, but also eliminates the pain and the risk of further infection associated with open wounds. A successful skin graft take requires a well vascularized and relatively sterile bed, as well as complete resolution of any surrounding infection. The author reviews the indications and techniques for obtaining a successful skin graft take. PMID- 7861326 TI - Hypertrophic and keloid scars. AB - Scar formation is discussed along with definitions of the three most common types of scars: normal, hypertrophic, and keloid. Several current forms of therapy designed to reduce or eliminate scars are presented. The use of silicone gel sheeting is reviewed as a newer solution for the treatment of many types of lower extremity scars. PMID- 7861327 TI - Three examples of Vietnamese footwear from the Vietnam conflict. PMID- 7861328 TI - S100 protein in oral biology and pathology. AB - The demonstration of S100 protein is used extensively for both research and diagnostic purposes in oral biology and pathology. This article reviews the structure and putative function of S100, technicalities of S100 immunohistochemistry, the cells of the oral and perioral tissues which express S100 and the possible significance of S100 expression in disease. PMID- 7861329 TI - Contact stomatitis to mercury associated with spontaneous mononuclear cell infiltrates in brown Norway (BN) rats with HgCl2-induced autoimmunity. AB - Light microscopy and immunocytochemistry have been used to study the tissue reaction to non-irritant concentrations of mercury painted onto the oral mucosa of genetically mercury-sensitive BN rats. Low-dose skin injections of HgCl2 in BN rats result in an autoimmune syndrome, including also a spontaneous migration of T lymphocytes into the oral mucosa. Our results show that such infiltrates confer an increased degree of reactivity (contact stomatitis) to HgCl2 painted onto the BN (Hg) rat oral mucosa. In contrast, results were negative in the LEW rat strain, which is also resistant to development of autoimmunity to skin-injected mercury. The possible involvement of mucosal mercury-loaded macrophages is discussed. The results are also discussed with respect to possible etiologic and pathogenetic mechanisms involved in the development of dental material (amalgam) associated lichenoid lesions of human oral mucosa. PMID- 7861330 TI - Immunolocalization of alpha 2, alpha 5, and alpha 6 integrin subunits in salivary tissue and adenomas of the parotid gland. AB - The localization of the integrin subunits alpha 2, alpha 5, alpha 6 was studied immunohistochemically in samples of normal salivary gland and in a series of 8 pleomorphic adenomas, 5 Warthin's tumors, and 2 basal cell adenomas. In normal salivary tissue, acinar and ductal cells expressed alpha 2 and alpha 6 chains at the basal cell pole facing the basement membrane. alpha 2 also localized at sites of cell-cell contact. No staining of the epithelial component was seen with alpha 5. The polarized expression of alpha 2 and alpha 6 subunits was retained in salivary adenomas. These subunits were present at the basal cell pole of solid nests, tubules and ducts of pleomorphic adenomas, as well as of the basal layer of the epithelium of Warthin's tumor, and of the trabecular structures of basal cell adenomas. The alpha 5 subunit was consistently expressed only by cells embedded in the myxoid or chondroid matrix of pleomorphic adenomas. We conclude that the pattern of a integrin subunit expression in salivary adenomas may be related to the "epithelial" or "mesenchymal" phenotype of the neoplastic cells. PMID- 7861331 TI - Adenoid cystic carcinoma of the palate with squamous metaplasia or basaloid squamous carcinoma? Report of a case. PMID- 7861332 TI - The development of English speech patterns of a 7-year-old Polish-speaking child. AB - The silent period hypothesis was investigated by examining the speech development of AO, a Polish-speaking child, who emigrated to the U.S. at age 7 years, 5 months, and placed in the second grade of a rural Missouri school district in which there was no instruction of English as a second-language. AO was observed for 6 years, 8 months, in order to study the development of his English speech patterns. During this interval, recordings were made of five sentences produced by AO at five different age points and with recordings from a control group of native and nonnative speakers were rated by native American speakers. AO's accent showed a gradual decline during the first year of residence, receiving a rating of near-native speech. By age 14 years, 6 months, he was rated as having native speech performance. Observations of his language, social, and school development indicated that AO remained essentially silent during the first 6 months, using two- and three-word sentences only when necessary, that his social development was normal, and that his school achievement was not impeded by his placement in the grade level appropriate for his age. The conclusion was reached that AO's silent period experience contributed significantly to his development of English speech patterns. PMID- 7861333 TI - The Edinburgh facial palsy clinic: a review of three years' activity. AB - Patients with facial palsy can present to almost all medical practitioners. From birth to old age the aetiologies of disease affecting the nerve range from congenital to the more common inflammatory, infective, traumatic and neoplastic. This paper reviews the Edinburgh Facial Palsy Clinic, its structure and function over a three year period. The methods of clinical investigation, special investigation and management strategies are discussed. The diversity of pathology seen over a three year period is presented, confirming the need for a team approach to the management of patients with facial palsy. PMID- 7861334 TI - Benign breast disease in Nigerian women: a study of 657 patients. AB - A 15-year combined retrospective (222 patients) and prospective (435 patients) evaluation of the pattern of benign breast disease in one region of the African tropics has been completed. Fibroadenoma constituted the largest group (55.6%), followed by mammary dysplasia (fibrocystic disease with fibroadenosis: 29.3%) and sclerosing adenosis (7.9%). Approximately one-third of women were under 20 years and two-thirds under 25. For the 435 patients in the prospective study, a late mean [SEM] age at menarche of 15.3 (2.1) years (controls: 14.2 [2.5], NS; early first full-term pregnancy: 20.4 [1.6] years, (controls: 21.1 [1.1], NS; parity 3.6 [1.7], (controls: 4.1), NS; and prolonged breast feeding (17.6 [2.2] months) did not appear to constitute risk factors to the development of benign breast disease among Nigerian women. PMID- 7861335 TI - An evaluation of the local reaction and biodegradation of calcium sodium alginate (Kaltostat) following subcutaneous implantation in the rat. AB - Kaltostat swabs were implanted subcutaneously in rats to evaluate their biodegradability and ability to evoke local tissue reactions. Implant sites were evaluated after 24 h and after 7 days, 28 days and 12 weeks. Histological sections showed no noticeable degradation of the Kaltostat within the 3 month observation period, contrary to some published reports. Following subsidence of a modest foreign body reaction, implants became embedded in thin fibrous sheaths which were infiltrated with vascular channels and fibroblasts. This study demonstrates that Kaltostat fibres are well tolerated following subcutaneous implantation in the rat model and present no obvious toxic risk or contraindication to their use as wound dressings or as haemostatic agents in general surgery. PMID- 7861336 TI - Efficacy of urgent thoracotomy for trauma in patients attended by a helicopter emergency medical service. AB - Over a 12-month period the Helicopter Emergency Medical Service underwent 1084 missions attending casualties in the London area. Sixteen patients required an emergency thoracotomy for resuscitation, nine of which were performed at the scene and seven in the emergency department. The median injury severity score of these patients was 29.9 (SIR 11.8) of which 11 had suffered blunt injuries. Medical attention at scene was administered 16.2 min (SIR 4.0) following the London ambulance service receiving the emergency call. Significantly longer time was spent attending patients who had a scene thoracotomy (35.1 min SIR 16.4) compared with those in whom the thoracotomy was performed in the casualty department. No patient in this series survived resuscitative thoracotomy. It is suggested that scene thoracotomy be abandoned and emphasis placed upon the rapid transport of patients to an emergency facility. This enables other resuscitative measures in addition to thoracotomy to be applied effectively and concentrated over a brief period by a multidisciplinary team. PMID- 7861337 TI - Can we really prevent gastrointestinal bleeding after head injury? Results of a recent audit. AB - This retrospective study looks at the severe head injury patients admitted to one unit in a year. Within this group, those with significant gastrointestinal bleeding were further studied to assess medical prophylaxis against this complication. A preliminary attempt is made to gauge whether such medication is appropriate, particularly with reference to H-2 antagonists. No firm conclusions can be drawn, but sufficient doubt remains to justify a prospective trial which is planned. PMID- 7861338 TI - How far to pass a nasogastric tube? Particular reference to the distance from the anterior nares to the upper oesophagus. AB - The length of the nasogastric tube inserted into a patient is frequently ill considered. If an inappropriate length of tubing is passed this may result in feeding difficulties or inadequate aspiration of gastric contents. This study assessed the optimal length by assuming that the oesophagus is 25 cm long and that the tip of a nasogastric tube should lie 10 cm below the gastro-oesophageal junction. The portion of tubing from the anterior nasal spine to the cricopharyngeus was calculated by superimposing a Ryles tube over a soft tissue lateral neck radiograph. Two hundred and forty cases were reviewed by three independent observers. The median distance was found to be 21 cm. It is recommended that nasogastric tubes are marked at 56 cm and this point be secured level with the nasal vestibule. PMID- 7861339 TI - Duplex ultrasound surveillance of infrainguinal bypass grafts: auditing the process. AB - The effectiveness of an infrainguinal bypass graft surveillance programme using duplex scanning was assessed over a 2-year period. Of 220 infrainguinal bypass grafts (123 vein and 97 PTFE grafts; 114 to the above knee level, 94 below knee and 12 distal to popliteal artery) in 203 patients, 208 (94.5%) were available for follow-up surveillance. The protocol called for duplex scans at 6 weeks, 3, 6, 9 and 12 months. Fifty-seven grafts (27%) were found to have a V1/V2 ratio equal to or greater than 1.5 and in this group 25 grafts occluded. The median time between primary operation and positive duplex finding was 4 months. Thirty nine grafts failed during follow-up (at time of analysis median follow-up was 12 months [range 2-83 months]). There were 18 interventions resulting from surveillance-detected stenoses. The median time between positive duplex finding and further investigation was 2 months. Further, there were significant differences in the site of abnormal findings between ePTFE and vein grafts. The value of a surveillance programme may be reduced if there are low rates of intervention and/or excessive delays in intervention following the demonstration of graft-related stenoses. Surveillance programmes and subsequent interventions need to be audited. PMID- 7861340 TI - Atypical mycobacterial lymphadenopathy in children--is it underdiagnosed? AB - Lymphadenitis due to atypical mycobacteria occurs primarily in the neck region of children, the most common organisms isolated are the Mycobacterium avium intracellulare (MAIS) group and M. malmoense. The nodes are unilateral and may be hot or cold. The infection is benign. There is little or no systemic upset and it is usually the preschool child who is affected. Routine haematological investigations are unhelpful, chest X-ray is clear and the Mantoux test may be positive or negative. Cultures are necessary to prove the diagnosis. The ideal treatment is total excision of the affected nodes and antituberculosis chemotherapy is not indicated. PMID- 7861341 TI - The management of acute sigmoid volvulus in Nottingham. AB - Forty previously undiagnosed cases of acute sigmoid volvulus presenting over five years in Nottingham are retrospectively reviewed. The average age was 71.6 years with an even sex ratio. Fifteen (38%) patients lived in nursing homes or institutions. At presentation, all had clinical features of large bowel obstruction, confirmed on plain abdominal X-ray. Sigmoidoscopy and rectal tube decompression was successful in 23 cases. The remaining 17 patients were treated surgically, within 24 hours, at which time the sigmoid was sutured to the abdominal wall (2 cases), resected and brought out as a colostomy (10 cases) or resected and primarily anastomosed (5 cases). Whilst in hospital, of those treated conservatively five died, and three from those treated surgically, four from those in which a colostomy was formed died and three from those in which a primary anastomosis was fashioned died. Of those that survived 11 from the conservative group had at least one recurrence, but none recurred following surgery. In conclusion, acute sigmoid volvulus affects an old and infirm population and carries a poor prognosis. Conservative management is initially preferable, but if emergency surgery is necessary a colostomy rather than primary anastomosis is indicated. PMID- 7861342 TI - Longterm indwelling urethral catheterization for neuropathic bladders--an audit. AB - An audit was performed on 17 patients with neuropathic bladders managed on longterm indwelling urethral catheters with a duration of at least eight years. The accumulated duration of continuous catheterization of this study group was at least 231 man years. The effects on the upper urinary tracts were studied by annual imaging alternating between limited intravenous urograms and ultrasonography, together with serum creatinine estimations. A grading system for upper tract changes was introduced. About a quarter of the patients on indwelling urethral catheter drainage developed early calyceal dilatation. Three patients were converted to suprapubic catheterization and three had ileoconduit diversion. The reasons were analysed. Although urine cultures were consistently positive with mixed organisms, all instances of clinical urinary tract infections were easily controlled by short courses of antibiotics. In six patients who had cystoscopic examinations, no tumour transformations were noted. Other complications encountered included bladder stones (2), clinically significant urethral fissuring (1) and bleeding per urethra (1). The three considerations for prescribing bladder management are discussed. With good catheter management and regular changes, we conclude that indwelling urethral catheter is a serious option for longterm drainage of neuropathic bladders. PMID- 7861343 TI - Needle prick injury to the surgeon--do we need sharp needles? AB - Needle prick injury is a well known hazard for surgeons and their assistants. This carries a risk of transmitting HIV and hepatitis infection. In this study the high incidence of sharp needle injury was confirmed (18.9%), with more than one third (8.7%) resulting in skin puncture. The highest incidence of injury occurred during hernia repair (27%) and abdominal wound closure (52%), where injury was sustained to the left index and middle finger as would be expected in right-handed surgeons. Blunt-tipped needles were used in 78 different procedures with technically satisfactory outcome particularly in abdominal wall wound closure and hernia repair, and even in colonic anastomosis, only two glove injuries were reported, with no skin injury. We concluded that the used of blunt tipped needles is a practical option in eliminating needle prick injury to surgeon's hands. PMID- 7861344 TI - The use of endoluminal ultrasound in the assessment of patients with faecal incontinence. AB - To determine the clinical value of endoanal ultrasonography in the assessment of patients with faecal incontinence, we have assessed 98 patients with neurogenic incontinence (median age 58 years, 85 women). Twenty-one patients with a history of previous anal surgery (13 men), 12 nulliparous women, and 73 women with an obstetric history (including eight with previous anal surgery) were assessed. All of the patients who had undergone surgery and 43 patients with a previous obstetric history had abnormalities identified by ultrasound. Endoanal ultrasound identified two internal sphincter injuries in patients who were suspected of having an external sphincter defect alone. In addition, in 18 patients who had an obstetric history but no documented obstetric trauma, defects were identified in the external sphincter by ultrasonography. The technique appears most useful in those patients with an obstetric history and/or a previous history of anal surgery. Symptoms of incontinence were most severe in those who had internal sphincter division. PMID- 7861345 TI - Fulminant pseudomembranous colitis (PMC) following triple therapy for Helicobacter pylori. PMID- 7861346 TI - Suction-tip dissecting scissors for pelvic surgery. PMID- 7861347 TI - Fractures of the humeral capitellum: Herbert screw fixation. AB - During the first half of 1991, five patients with displaced fractures of the humeral capitellum were managed by open reduction and fixation of the capitellar fragments with Herbert bone screws. All patients had stable, painfree elbows at follow-up, with no restriction of normal daily activities. There were no evidence of early avascular necrosis of capitellar fragments, even where soft tissue attachments of small fragments had been injured. This method of fixation allows accurate restoration of the articular surface of the humero-radial joint and may therefore contribute to the excellent functional results following this injury in these patients. PMID- 7861348 TI - Hepatitis B immunization: a survey of orthopaedic surgeons. AB - In 1988 a survey of 72 orthopaedic surgeons was performed to determine the rate of immunization against the hepatitis B virus (HBV). 54% had received the vaccine. Offers of immunization from occupational health departments doubled the rate of uptake. Only 51% of surgeons had been offered this service. A repeat survey was performed in 1992 to assess the effect of recent publicity on viral transmission during surgery. 81% have now received the vaccine. PMID- 7861349 TI - A 5-10 year follow-up of the Sheehan total knee endoprosthesis in Tayside. AB - The Sheehan total knee endoprosthesis has been widely used since 1971. It takes the form of a semi-constrained hinge with intramedullary stems cemented into the femur and tibia for fixation. In Tayside the prosthesis has been in use since 1980. The clinical impression was that the prosthesis was not performing well and formal assessment of surviving prostheses was therefore carried out using the Hospital for Special Surgery (HSS) scoring system. Thirty-seven patients were available for follow-up, 15.6% of whom had good results while 40% had poor results according to this assessment. At review, 31% of patients had undergone revision surgery or were awaiting such surgery. This compares poorly with reported results of surface joint replacements. In the light of these results the authors feel that the Sheehan knee replacement is now obsolete. PMID- 7861350 TI - Home traction in the management of femoral fractures in children. AB - Fracture of the femur in children is a common problem which can be managed in a variety of ways. We treated such fractures in children up to the age of 13 by immobilization in a Thomas splint, after reduction, if necessary, and traction in hospital. After a short period, traction was continued at home using a mobile frame with the Thomas splint. The results of such home traction were assessed in terms of both healing of the fracture and any complications and of the parental attitudes to treatment at home. It was found that traction at home was an acceptable method for the management of such fractures. Results were comparable to other methods of treatment and parental satisfaction was very high, providing there was adequate surveillance by the district nurse and immediate access to advice. The cost-savings of such a treatment are significant. PMID- 7861351 TI - [Value and future of electron beam computed tomography]. AB - Mecanic computed tomography would probably never reach the acquisition brevity obtained by EBT. This machine is the best for exploration of cardiovascular diseases, and non cooperative patients, and for cine and flow studies. Morever, there are never tube cooling delays or interruptions in any procedures. Its disadvantages are the price, the impossibility to tilt the gantry, and the computer which are to be improved. With "Evolution", Siemens proposes now improvements with the CVS mode and a computer release without increasing of the price. PMID- 7861352 TI - [Presentation of the electron beam scanner (Imatron C100 scanner)]. AB - Principles of Electron Beam CT are described and compared to conventional CT. Fast acquisitions and a short exposure time are the major qualities of the machine. Despite of a lower spatial resolution than in mechanical CT it allows exploration of moving organs and especially morphological and dynamic heart studies. The new possibilities of the Continuous Volume Scanning seems to present an promising future outlook. PMID- 7861353 TI - [Dosimetry with Imatron]. AB - Although the Imatron is based on a technology different from that of conventional CT scanners, its physical principle is comparable. For this reason dosimetric studies were carried out in the same manner that is by employing small thermoluminescent dosimeters. The results obtained with this technique for the four specific protocols of the Imatron indicated surface doses between 0.7 and 15.7 cGy and between 0.1 and 7.2 cGy at surface of the slice. The weakest doses were recorded during cardiac exams for which this type of CT scanner was designed and developed. This highest doses were delivered for scans of the head region. PMID- 7861354 TI - [Investment and operating costs of the electron beam scanner at the Broussais Hospital]. AB - Cost of Imatron and of its building was 150,000,000 FF in 1989, highly more expensive than for other CT. Cost of "maintainance" is only 9.5% of its acquisition price against 21% for other CT. The replacement of high power and detectors is less frequent in Imatron than X ray tubes in the other CT. Imatron was often out of order during the 2 first years because of high power. Now the time devoted to break down is only 2.5%. A slice price is 4.75 FF for Imatron and the mean slice price is 7.38 FF for the other Assistance Publique CT (from 4.88 to 10.53). PMID- 7861355 TI - [Dynamic cardiovascular studies with electron beam computed tomography]. AB - Electron Beam CT (EBCT) is still emerging as a new functional imaging procedure in providing high morphological studies and dynamic quantitative functional data. Morphological EBCT studies have previously proven their usefulness in pathologic conditions of the thoracic aorta, in congenital diseases, in cardiac masses or tumors... Functional studies achieved using cine mode and/or flow mode are used to assess both mobility and perfusion of structures. Such dynamic analysis have confirmed that their applications will have a major impact on the knowledge of cardiac physiology, the understanding of cardiovascular diseases, if not in daily patient care. For instance, in studies on ventricular function, among the imaging modalities in current use, EBCT is probably most accurate for the evaluation of systolic regional or global function. EBCT is a cross-sectional imaging methods which overcome an important limitation shared by most other imaging modalities, namely the superimposition of overlapping cardiac and thoracic structures. Since in the method high spatial, contrast, and temporal resolution tomography displays the myocardial wall itself, an accurate delineating of endocardial and epicardial contours in contiguous levels can be obtained. Further developments in computer automated analysis from dynamic EBCT studies have to be carried out to gain clinical acceptance and to facilitate the routine. PMID- 7861356 TI - [Electron canon computed tomography. Technique and clinical applications in cardiac imaging]. AB - Electron Beam CT (EBCT) was initially devoted to both dynamic and morphological cardiac studies. ECG gated slices acquired in 100 milliseconds produce cardiac images without motion artefacts. Intracavitary tumors and thrombus are clearly detected and EBCT contributes to the stagging and follow-up of masses. Exploration of congenital abnormalities such as pulmonary atresia can be performed even in newborns. EBCT allows the diagnosis of tiny modifications of coronary arteries, endocardium or pericardium. EBCT offers a new modality of cardiac imaging which gives complementary informations to other modalities. PMID- 7861357 TI - [Electron beam scanner and thoracic transplantation]. AB - To follow an heart transplantation, EBCT is more precise than ultrasonography and scintigraphy to calculate a stroke volume. In lung transplantation, it is important before surgery to know the value of right ventricule stroke volume in order to choice the surgical protocol. After lung transplantation SFE helps to follow the patient to look after complications, to drain a collection or to guide a biopsy. SFE contribution is discussed in rejection, infectious diseases, detection of immuno-induced carcinomas, in bronchiolitis obliterans and recurrence of the primitive disease. PMID- 7861358 TI - [Evaluation of the right ventricular function for lung transplantation. Value of the electron beam scanner]. AB - Several invasive or not invasive technics were used to evaluate right ventricular insufficiency associated to severe chronic pulmonary insufficiency. But none of them were very accurate and now the use of EBT appears as a real improvement. We performed a prospective study with 50 patients waiting for a lung transplantation and we compared the values of right ventricular function obtained by EBT to those obtained by nuclear medicine and catheterism. Accuracy of EBT for left ventricule evaluation has already been proved. Stroke volumes calculated by EBT in right and left ventricules are similar and this constitutes a good validation of the method for right ventricule evaluation. Correlations with hemodynamic measurements are poor and nuclear medicine technics underestimate the ejection fraction. So, EBT is recommended for right ventricular study before and after lung transplantation. PMID- 7861359 TI - [Detection and significance of coronary calcinosis]. AB - Coronary calcifications (CC) are the witness of atheromatous disease because they lies in intima. This is a best stamp of coronary atheromatosis than all the well know risk factors. CC scores is perfectly estimated by EBT. The reproductibility expressed in logarithm data is 7.2% in inter-examination, 1.3% in inter observers, 2% in intra-observers [4]. CC detection is more specific in young population than in old population because CC appear and increase with age in asymptomatic patients [12]. But the score curve raised higher in symptomatic than in asymptomatic subjects. A patient with an abnormal score for his age will have 5 to 10% of ischemic cardiac disease during the following 6 months [11]. PMID- 7861360 TI - [Contribution of the electron beam scanner (Imatron) in aortic pathology]. AB - Electron Beam CT (SFE, Imatron) uses electron beam to generate X rays. This allows the shortest acquisition time today available (50-100 ms). It is the best CT examination for moving structures. In vascular disease arterial wall study is the most important end point, especially in aortic pathology. EBCT is effective in aortic aneurysm, dissection and aortitis diagnosis. It allows a pre-surgical mapping of the lesion and follow-up. We believe that EBCT is superior to other diagnostic mean in the assessment of the ascending aorta and of small arterial lesions. PMID- 7861361 TI - [Angioscanner analysis using Imatron C100 in 44 cases of hepatic tumors]. AB - We studied 44 patients with focal benign (n = 13) or malignant (n = 31) liver tumors prouved by histology or follow-up. The flow mode was acquired by electron beam CT (EBCT) after injection (35 cc at 6 ml/sec): 20 slices with a 400 ms exposure time. We looked for abnormal vessels and density curves inside the tumor, liver and aorta. We describe arterial vascularization in most cases (type 1) and particularly in all the hepatocarcinomas (n = 15) associated with abnormal vessels, and also in rare tumors (n = 4). For benign lesions like angiomas (n = 9) we showed surrounding the mass arterial vascularization in add to the typical aspect (type 3); for nodular hyperplasia (n = 3) arterial blush was associated with the last part of the tumoral curve at the same level as liver. Most often metastasis (n = 13) had no central vascularization and a slight peripheral density increased (type 2). Flow mode by EBCT allows a good density curves analysis particularly at arterial time. PMID- 7861362 TI - [Measurement of global and separate renal blood flow using cine-computed tomography]. AB - EBCT flow study offer a promising new approach to measure the renal blood flow. In vitro and in vivo studies were performed to resolve methological problems such as checking the linear relation between contras concentration and Hounsfield units or determination of the Treshold used for the mapping. First measurements of renal volumes and flow performed in patients showed expected values. PMID- 7861363 TI - [100 years of radiology and 80 years of the Journal de Radiologie]. PMID- 7861364 TI - [Diffuse toxoplasmic encephalitis in a non-immunosuppressed patient]. AB - Diffuse encephalitic toxoplasmosis is an unusual presentation of toxoplasmosis, in which neuroradiological investigations may not show focal abcesses. Until now it was only reported in immunocompromised patients. In immunocompetent patients, cerebral toxoplasmosis is very unusual, and appears as multiple abcesses, like the classic form in immunocompromised patients. We report the case of an immunocompetent patient who presented a diffuse encephalitic toxoplasmosis; CT and MR examinations showed only nonspecific features of brain swelling and cortical infarct due to vasculitis. PMID- 7861365 TI - [Compression of the subscapular nerve in the spino-glenoid tract by a synovial cyst]. AB - We observed a case of synovial cyst in the shoulder joint leading to spino glenoid symptomatology in a weight-lifter. Explorations included standard radiography, echography and magnetic resonance imaging. Differentiation between a true cyst and a pseudo-cyst was basedose presence of a synovial membrane. Mechanical contraints appear to be the most frequently suspected aetiology of spinoglenoid cysts. Echography cannot always confirm the liquid nature of the formation due to the close bone. Magnetic resonance imaging gives good tissue characterization and good topographic analysis. Gadolinium injection appears to be important for differential diagnosis with neurogenic tumours. PMID- 7861366 TI - [Myxoid liposarcoma. MRI imaging]. AB - PURPOSE: Myxoid liposarcoma is the most common type of liposarcoma (approximately 40 to 50% of all liposarcomas). The main tissue component is a myxoid matrix present primarily in extracellular compartments; proliferating lipoblasts account for less 10% of the tumor: MRI appearances are not typical for lipomatous tumor. Nevertheless histological features may permit understanding MRI findings and identifying patients with myxoid liposarcoma. MATERIALS AND METHODS: Clinical history and radiologic images of 7 patients with histologically verified myxoid liposarcoma were retrospectively studied. In all patients the tumor presented in a lower extremity as a painless, slowly growing mass. MR images were available for review in all cases (T1- and T2-weighted images); in addition fat-suppression before and after gadolinium enhancement were assessed with T1-weighted sequences. RESULTS: MRI examination revealed an "encapsulated" tumor, non infiltrating and septated. On T1-weighted sequences all the lesions show lacy, amorphous and linear foci of high signal within a low signal of the tumor due to the predominance of a myxoid matrix. The high sensitivity of MRI demonstrates the presence of small areas of high signal and fat-suppression technique is valuable for characterizing soft-tissue tumors: suppression of high signal intensity on fat-saturated T1-weighted images indicates the presence of fatty tissue components. CONCLUSION: Clinical correlation with MRI appearances on T1-weighted sequences (in addition to fat-suppression technique) may suggest the possibility of myxoid liposarcoma. PMID- 7861367 TI - [Magnetic resonance imaging of lesions of the superficial plantar fasciitis]. AB - MRI is an efficient imaging modality to establish the diagnosis of plantar fascia tear and plantar fasciitis. MRI allow to differentiate recent rupture from scar and fasciitis. PMID- 7861368 TI - [Rare causes of ossification of the posterior common vertebral ligament causing cervical compression. Apropos of 2 cases]. AB - The ossification of the posterior longitudinal is always responsible of cervical myelopathy. Radiological study and the CT scan, are able to precise the level, the morphologic and associated abnormalities of this lesion. Two cases of ossification of the posterior longitudinal ligamentum with cervical myelopathy are reported. The radiologic studies determined the etiology, in the first case, it was fluorosis and the second DISH disease. PMID- 7861369 TI - [Hepatic angiomyolipoma. Magnetic resonance imaging and imaging by CT-xray]. AB - A case, is reported of a 40 year-old woman with a "form fruste" of tuberous sclerosis, multiple angiomyolipomas of the kidney, and an angiomyolipoma of the liver. On magnetic resonance imaging the hepatic mass was markedly hyperintense to liver on short TR/short TE spin-echo sequence. Spiral computed tomography during arterial portography showed hepatic mass in the right hemiliver with areas of negative attenuation values suggesting fat content. Pathologic examination of the resected specimen confirmed the diagnosis of an angiomyolipoma of the liver. Computed tomography during arterial portography is a commonly performed preoperative imaging modality. Therefore, recognition of angiomyolipoma of the liver by this technique is important, because this benign mesenchymal neoplasm may not require resection. PMID- 7861370 TI - [Type IA glycogenosis with acute pancreatitis]. AB - Type IA glycogenosis, or von Gierke disease, is the most common among the glycogenoses with enlarged liver. Acute pancreatitis is a rare manifestation of type IA glycogenosis and has been attributed to elevated serum fat levels. We report a case of type IA glycogenosis with acute pancreatitis. The radiologists should be familiar with the computed tomography findings in this rare complications of type IA glycogenosis. PMID- 7861371 TI - [Discovery of prehepatic opacity in a scan performed for acute abdominal painful syndrome]. PMID- 7861372 TI - [Renal hydatid cyst of uncommon aspect. Apropos of a case]. AB - The authors report an unusual ultrasonographic aspect of hydatic cyst of kidney. They point out the importance of computed tomography in atypic hydatid cysts. Semiologic analysis of ultrasonographic and scanographic patterns, leads usually to the diagnosis of atypic hydatid cyst, in addition with serologic examination. PMID- 7861373 TI - [Uro-oxalic renal lithiasis. Certain characteristics]. AB - In a paper published in 1974, it was reported that uro-oxalic stones are found more often in subjects with group O than with group A blood types although the proportions of these two blood types are approximately equivalent in the French population. The present work confirms these data, the ratio of group O to group A renal lithiasis being approximately 3 to 1. In a paper published in 1987, uro oxalic stones were found to occur preferentially on the left side: 84 on the left and 39 on the right. The present work confirms this notion since in 57 cases, stones were bilateral in 2 cases, on the left in 39 and on the right in 16. Extra corporeal shock wave lithotripsy was performed in 40 of the 57 cases and showed that uro-oxalic stones are most resistant to shock-waves than the other types of stones. They are about as hard as calcium oxalate monohydrate stones or harder in certain cases: A mean of 3,865 shock-waves were required in the 40 cases of the uro-oxalic lithiasis treated with the HM3 Dornier device, while the mean number of shock-waves required for all types of stones in general varies from 2,000 to 2,500. In 4 cases, 5,000 or 6,000 high power shock-waves (7,000 in one session and 9,500 in two sessions) had to be used to obtain a satisfactory result. The calcium oxalate part of these stones is almost always composed of calcium oxalate monohydrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861374 TI - [MRI of uterine leiomyosarcoma. Apropos of 2 cases]. AB - Prognosis is poor for uterine leiomyosarcomas. Diagnosis is often an unexpected pathology discovery after hysterectomy for fibroma. Prognosis depends on the degree of locoregional extension and thus on early diagnosis. Echography and computed tomography scan are note very specific. There is little literature on imagining studies, and particularly on MRI in this pathology. Yet MRI, especially the T2 weighted sequences, is quite interesting for evaluating tumour extension in the uterus. It can be used whenever an abnormal increase in size is observed during the per- or postmenopausal period in a women with a fibroma. We report two cases of uterine leiomyosarcoma explored by MRI and review the literature. PMID- 7861375 TI - [Giant bronchopyocele. General and radiological characteristics. Apropos of a case]. AB - A case of giant bronchocele is reported. This lesion is due to a mucus and pus filled dilatation of the bronchial tree proximal to a stenosis. The latter can be either congenital or acquired, or in the context of a diffuse bronchopathy, which can be responsible for a functional stenosis. Both plain radiography and computed tomography findings are diagnostic. The etiology of the abnormality however represents an important problem to be solved. Further, a thoractomy is often necessary, except in those case arising in the context of a diffuse bronchopathy, which usually resolve either spontaneously or following medical treatment. PMID- 7861376 TI - [Beginnings of radiology in Lyon]. PMID- 7861377 TI - Induction of superovulation in DD mice at different stages of the oestrous cycle. AB - This study examined the developmental capacity of oocytes in DD mice after they had been injected with pregnant mares' serum gonadotrophin at different stages of the oestrous cycle. The superovulation of mature DD mice at pro-oestrus, oestrus and metoestrus resulted in a large yield of viable embryos. The proportion of abnormal embryos was highest after injection of pregnant mares' serum gonadotrophin at dioestrus. The pool of viable oocytes was most synchronized with normal development after the hormone was injected at oestrus. The results demonstrate that oocytes of different morphology could be induced to ovulate. The developmental capacity of oocytes of different morphology is discussed. PMID- 7861378 TI - Differences in pronucleus formation and first cleavage following in vitro fertilization between pig oocytes matured in vivo and in vitro. AB - To elucidate the developmental differences occurring after in vitro fertilization (IVF) of pig oocytes matured either in vitro (n = 1934) or in vivo (n = 1128), the present experiment investigated the morphological changes from penetration to the two-cell stage. Oocytes were examined every 2-4 h from 2 to 32 h after in vitro insemination to study sperm penetration, male and female pronucleus formation, synkaryosis and first cleavage. The penetration rate was significantly higher (P < 0.05) for in vivo matured oocytes (69.8%) than for in vitro matured oocytes (35.0%). Penetration of spermatozoa into the ooplasm was first recorded 6 h (in vitro matured oocytes) and 4 h (in vivo matured oocytes) after addition of the spermatozoa to the oocytes. For both in vivo and in vitro matured oocytes, 2 h were required for sperm head decondensation. However, maximum sperm head decondensation occurred 2 h later in in vitro matured oocytes. Within 6 h, 41.7 +/- 5.6% of the in vivo matured oocytes had completed second meiotic division, whereas only 20.8 +/- 6.5% of the in vitro matured oocytes reached this developmental stage (P < 0.01). For in vitro matured oocytes, male pronucleus formation was retarded 2-4 h after onset of insemination and development of the female pronucleus was enhanced compared with in vivo matured oocytes. Synchronized opposing pronuclei were observed 14 h after insemination in in vitro matured oocytes and after 8 h in in vivo matured oocytes. Synkaryosis was first observed at 16 and 18 h in in vivo and in vitro matured oocytes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861379 TI - Active immunization against melatonin in Ile-de-France ewes and photoperiodic control of prolactin secretion and ovulatory activity. AB - An experiment was conducted to determine whether active immunization against melatonin could modify the perception of abrupt photoperiodic changes in ewes. Two groups each containing six intact Ile-de-France ewes were submitted to alternate periods of short days for 2.5 months and long days for 2.5 days for about 70 weeks. Three series of active immunizations against a melatonin conjugate were carried out during the first of the three long-day periods. Control ewes were actively immunized at the same time against human serum albumin. Blood samples were taken once a week throughout the experiment to measure antibody titre and affinity, and prolactin and progesterone concentrations. Sera of all treated ewes demonstrated higher antibody titres than those of control ewes. Antisera were highly specific, as evidenced by the absence of displacement of iodinated melatonin in the presence of ten melatonin metabolites. Significant effects of photoperiod and of the interaction between treatment and photoperiod on prolactin concentration were detected. Prolactin concentrations in plasma of the control ewes were high during long days and low during short days. However, in the treated ewes, with the exception of the first period of long days, prolactin concentrations were not influenced by photoperiodic changes. Ovulatory activity of control ewes, as demonstrated by progesterone measurements, was stimulated by short days and inhibited by long days. In contrast, ovulatory activity of treated ewes, after a response identical to that of control ewes after the first photoperiodic shift from long to short days, showed a complete desynchronization of ovulatory activity relative to photoperiodic changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861380 TI - Identification of stage-specific changes in protein secretion by isolated seminiferous tubules from rats following exposure to short-term local testicular heating. AB - The objective of this study was to identify the early (after 4 and 24 h) effects of short-term local testicular heating (43 degrees C for 30 min) on the secretion of proteins by seminiferous tubules isolated from adult rats at stages II-V, VI VIII or IX-XII of the spermatogenic cycle, and cultured in vitro for 24 h with [35S]methionine. Incorporation of [35S]methionine into secreted and intracellular proteins was assessed and the pattern of protein secretion was evaluated using two-dimensional SDS-PAGE. Seminiferous tubules isolated from control rats exhibited the characteristic, androgen-dependent increase in protein secretion at stages VI-VIII. At 4 h after exposure to local testicular heating, seminiferous tubules at these stages showed a significant increase (P < 0.001) in the overall incorporation of [35S]methionine into secreted proteins, whereas seminiferous tubules at stages II-V and IX-XII showed no significant change. In marked contrast, seminiferous tubules isolated from rats 24 h after local testicular heating showed a significant decrease in the incorporation of [35S]methionine into secreted proteins at stages VI-VIII (P < 0.001) and to a lesser extent at IX XII (P < 0.05), whereas seminiferous tubules at stages II-V showed no change in incorporation. Prior treatment to maintain normal intratesticular concentrations of testosterone in heat-exposed rats failed to prevent these changes. Similar results were obtained when incorporation of [35S]methionine into intracellular proteins was evaluated 4 and 24 h after exposure to local testicular heating.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861381 TI - Delayed luteolysis and suppression of testosterone secretion after recombinant ovine interferon treatment in goats (Capra hircus). AB - Oxytocin at a dose of 100 iu injected s.c. daily into goats (Capra hircus) between day 3 and day 6 of the oestrous cycle caused a significant increase in testosterone secretion and luteolysis compared with saline-treated animals. Intrauterine administration of recombinant ovine interferon tau (80, 160 or 320 micrograms day-1) between days 12 and 18 of the oestrous cycle, or concomitantly (80 micrograms day-1) with oxytocin between day 3 and day 7, delayed luteolysis and blocked the increased release of testosterone. It is suggested that recombinant ovine interferon tau can act as an antiluteolytic agent in goats. PMID- 7861382 TI - Increase in postimplantation development of cultured mouse embryos by amino acids and induction of fetal retardation and exencephaly by ammonium ions. AB - The effects of amino acids and ammonium on the postimplantation development of cultured preimplantation mouse zygotes were assessed. Development after transfer revealed that the mouse embryo undergoes a switch in nitrogen requirements during the preimplantation period. Although Eagle's nonessential amino acids and glutamine supported the highest implantation and fetal development rates per embryo transferred when zygotes were cultured for 48 h, by 93 h of culture the highest implantation rate was observed when all 20 amino acids were in the culture medium. Furthermore, fetal development per implantation at 69 and 93 h of culture was increased only in the presence of essential amino acids without glutamine. The beneficial effects of amino acids on postimplantation development when embryos were cultured for 4 days required that the medium be renewed after 48 h (at the 6-8-cell stage) to alleviate the build-up of ammonium. Ammonium was shown to induce fetal retardation and exencephaly in a time- and concentration dependent manner. Renewal of amino-acid-free culture medium reduced fetal mass, providing indirect evidence for the production of an embryo-derived growth factor capable of stimulating postimplantation development. These data demonstrate that inclusion of amino acids in the culture medium for preimplantation embryos significantly increases postimplantation development the preimplantation mouse embryo changes its nitrogen requirement as development proceeds, nonessential amino acids increase the implantation rate while the essential amino acids enhance fetal development, and ammonium in the medium retards fetal development and induces the neural tube defect exencephaly. PMID- 7861383 TI - Ion dependence of resting membrane potential of rat spermatids. AB - The membrane potential of rat spermatids was estimated as -22 +/- 2 mV (mean +/- SEM) using three independent methods: using oxonol as a fluorescent membrane potential sensitive probe, from the passive distribution of hydrogen ions and from whole-cell patch-clamp records. The estimated permeability ratios PK+:PCl- and PNa+:PCl- of the plasma membrane of rat spermatids were 1.0 and 0.3, respectively. These data indicate that the high luminal K+ concentration found in seminiferous tubules could partially close voltage-sensitive calcium channels in these cells. PMID- 7861384 TI - Preservation of chick primordial germ cells in liquid nitrogen and subsequent production of viable offspring. AB - Conservation of genetic material in chickens was attempted by preserving primordial germ cells in liquid nitrogen. Primordial germ cells collected from the blood of embryos at stage 13-15 of White Leghorn and Barred Plymouth Rock breeds were concentrated by Ficoll density gradient centrifugation. The primordial germ cells were then suspended in a freezing medium containing 10% dimethyl sulfoxide. The temperature of the cell suspension was decreased by 1 degree C min-1 to -80 degrees C; the suspension was then placed in liquid nitrogen (-196 degrees C) and stored for 4-5 months. The cell suspension was thawed by taking it out of liquid nitrogen and placing it in water at 4 degrees C. The viability of the frozen-thawed primordial germ cells was 94.2%. One hundred frozen-thawed cells were injected into the bloodstream of recipient embryos (stage 14-15) from the other breed, from which blood had been drawn before the injection. These embryos were cultured in recipient eggshells until hatching. Viable offspring derived from the frozen-thawed primordial germ cells were obtained by mating male and female germline chimaeras or by mating the chimaeras with Barred Plymouth Rock chickens, and the offspring showed normal reproductive performance. This technique for cryopreservation of primordial germ cells giving rise to viable offspring makes it possible to conserve genetic material in avian species. PMID- 7861385 TI - Involvement of endogenous opioids in the regulation of LH and testosterone release in the male horse. AB - To investigate the involvement of endogenous opioids in the regulation of gonadotrophin release in male horses, effects of the opioid antagonist naloxone (0.5 mg kg-1 i.v.) on plasma LH and testosterone concentrations and the possible influence of season and of gonadal steroids were investigated. To determine quantitative as well as qualitative changes in gonadotrophin release, LH concentrations were measured by radioimmunoassay and by an in vitro bioassay. Experiments were performed in May, August and December. In stallions, basal LH secretion in May and August was significantly higher than in December (May versus December: P < 0.01; August versus December: P < 0.05); plasma testosterone concentrations were highest in August (August versus May: P < 0.05, August versus December: P < 0.001). The basal bioactive LH concentration and the ratio of bioactive:immunoreactive LH in stallions were highest in May. Therefore, in addition to seasonal changes in quantitative LH secretion, the bioactivity of LH in the circulation also undergoes seasonal variations. Bioactive LH concentrations and the bioactive:immunoreactive ratio in geldings were higher than in stallions. Naloxone caused a significant increase in LH release in stallions in August and December (P < 0.001); no significant increase was found in May (P = 0.06). In geldings, naloxone did not induce any changes in LH secretion; in stallions, a highly significant correlation was observed between basal testosterone concentrations and the LH increment after injection of naloxone (P < 0.001). In August and December, the bioactive:immunoreactive ratio increased significantly (P < 0.05) after injection of naloxone in stallions, indicating a preferential release of LH molecules with high bioactivity. The bioactive:immunoreactive ratio did not change after naloxone injection in May. The naloxone-induced LH release was followed by a significant increase in plasma testosterone concentrations in stallions in August (P < 0.001) and December (P < 0.05). In conclusion, endogenous opioid systems are involved in the regulation of LH and testosterone secretion in stallions. These mechanisms undergo seasonal changes: their activity is increased during winter and decreased during the breeding season. By affecting LH release, endogenous opioids, at least in part, regulate seasonal changes in reproductive activity in the stallion. PMID- 7861386 TI - Agonist and antagonist specificities of decidual prostaglandin-releasing oxytocin receptors and myometrial uterotonic oxytocin receptors in pregnant rats. AB - This paper describes further pharmacological characterization of the decidual prostaglandin-releasing oxytocin receptors and the myometrial uterotonic oxytocin receptors in the uterus of the pregnant rat. The effects of oxytocin, arginine vasopressin and their related agonists and antagonists on the release of PGF2 alpha were studied in vitro on isolated uteri from rats on day 19-20 of pregnancy that had been incubated in Krebs buffer, pH 7.4, at 37 degrees C. The concentration of PGF2 alpha in the media was measured using specific radioimmunoassays. It was found that the decidual and myometrial oxytocin receptors exhibit different ligand specificities. Of the agonists tested, oxytocin and arginine-vasopressin stimulated PGF2 alpha release in a dose dependent manner. Arginine-vasopressin has only 3% of the uterotonic potency of oxytocin, but was found to have 16% of its PGF2 alpha-releasing activity. [4 Threonine, 7-glycine]oxytocin, a highly potent and selective uterotonic oxytocin analogue, had no detectable prostaglandin-releasing activity at a dosage 30 times higher than oxytocin. However, 1-deamino-[8-D-arginine]vasopressin, a highly potent and selective antidiuretic arginine-vasopressin analogue, which has only 10% of the uterotonic activity of arginine-vasopressin, was as potent as arginine vasopressin in prostaglandin-releasing activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861387 TI - Effect of exogenous oxytocin on the leakage of lactose from the mammary gland and on suckling-induced plasma prolactin in the lactating rat. AB - The leakage of lactose from the mammary gland into plasma and the increase in the suckling-induced concentration of prolactin in the plasma of oxytocin-injected lactating rats suckling different numbers of pups were investigated. Rats nursing eight pups were isolated from their litter for 6 h and injected i.v. with either 1 iu oxytocin or saline and allowed to resuckle either two, eight or 12 pups for 1 h. The concentration of lactose in plasma increased significantly in rats injected with oxytocin and allowed to resuckle two or eight pups; however, there was no difference in rats allowed to resuckle 12 pups. When compared within oxytocin-injected groups, the concentration of lactose was significantly lower in rats allowed to resuckle eight or 12 pups than in rats allowed to resuckle only two pups. Plasma prolactin concentrations increased during the suckling period in mothers suckling either eight or 12 pups, and oxytocin diminished the increase in prolactin concentration in both groups. In rats suckling two pups, prolactin release was not observed. The second objective of this study was to determine the relationship between the leakage of lactose from the mammary gland by oxytocin injection and suckling. Mothers that had the three left nipples of their mammary glands occluded were isolated from their litter of eight pups for 6 h and were allowed to resuckle with eight pups for 1 h. At the start of resuckling, 0.01, 0.1 or 1 iu oxytocin was injected i.v.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861388 TI - Effect of nutrition on seasonal patterns of LH, FSH and testosterone concentration, testicular mass, sebaceous gland volume and odour in Australian Cashmere goats. AB - The effects of season and diet on LH, FSH and testosterone concentrations, testicular mass, sebaceous gland volume and male odour were examined in mature Australian cashmere goat bucks fed ad libitum with diets of low or high quality for 16 months under natural photoperiod at 29 degrees S, 153 degrees E (n = 6 per treatment). Each week plasma was sampled, the bucks were weighed, scored for male odour and assessed for testicular mass based on scrotal circumference. Each month a skin sample was taken from the occipital region for histological assessment of sebaceous gland volume. For each variable there was a clear circannual cycle that was significantly influenced by dietary treatment. In bucks fed the low-quality diet, the timing of seasonal changes in LH and testosterone concentration, sebaceous gland volume and odour score was similar, with a mid-autumn peak. In each case the high-quality diet advanced, extended the duration and increased the magnitude of the seasonal increase. FSH concentrations peaked in late spring (in bucks on the high-quality diet) or summer (in bucks on the low-quality diet), reaching a nadir in early winter. The high-quality diet significantly increased concentrations only in the last 2 months of the experiment (spring). There was no overall association between these variables and change in testicular mass; instead, it was strongly correlated with voluntary feed intake and change in body mass, themselves subject to seasonal variation with a winter or spring peak. The high-quality diet induced large increases in body mass and testicular mass during the first months of the experiment without influencing the seasonally low concentrations of FSH, LH and testosterone present at the time. These results demonstrate that the male, like the female, Australian cashmere goat, exhibits marked reproductive seasonality, and that nutrition is a powerful modulator of the seasonal cycle. They suggest that testosterone concentration, sebaceous gland volume and odour score are ultimately dependent upon LH secretion, which appears to be under strong seasonal (photoperiodic) control, with the effects of enhanced nutrition limited to periods when photoperiodic inhibition is waning. However, seasonal regulation of testicular mass, and therefore sperm production, appears to be primarily dependent on changes in voluntary feed intake and growth, with the seasonal cycle of testicular mass more a consequence of the seasonal appetite or growth cycle than of changing gonadotrophin concentrations. PMID- 7861389 TI - Morphology and subsequent development in culture of bovine oocytes matured in vitro under various conditions of fertilization. AB - The objective of these experiments was to evaluate factors affecting in vitro fertilization of bovine oocytes matured in vitro, and their subsequent development to blastocysts. In Expts 1 and 2, sperm concentration, spermatozoa and oocyte incubation time, motility enhancers and semen source were manipulated. Fluorescent microscopy of microtubules and chromatin was used to observe sperm penetration rate, sperm aster formation and chromatin decondensation. Oocyte penetration rates were affected by sperm concentration but not by spermatozoa and oocyte incubation time. The effect of sperm concentration was due primarily to changes in polyspermy and not monospermy. Motility enhancers had no effect on any parameter measured. In Expt 3, oocytes were matured for 17, 22, 28 and 34 h before fertilization and evaluated for fertilization rates, morphology of cortical granules and exocytosis and blastocyst development. A domain free of cortical granules that was associated with the metaphase chromatin was not observed in mature bovine oocytes. As oocytes matured from 17 to 34 h, the distribution of cortical granules progressed from clustered to diffuse. Although monospermic fertilization rates were similar and cortical granule exocytosis occurred in all groups, polyspermy increased with maturation time. Development to blastocysts increased from 17 to 22 h of maturation but decreased thereafter with increasing maturation time. These results suggest that polyspermy can be reduced by adjusting sperm concentration and spermatozoa and oocyte incubation time with little effect on monospermic fertilization. Increased polyspermy with increased maturation time was not due to a lack of cortical granule exocytosis. PMID- 7861390 TI - In vitro development of day 2 embryos obtained from young, fertile mares and aged, subfertile mares. AB - This study was designed to investigate the development of day 2 embryos obtained from young and aged mares, co-cultured with oviductal epithelial cells obtained from mares in each age group in a 2 x 2 crossover design. Young, fertile mares (n = 19; 2-7 years of age) and aged, subfertile, mares (n = 16; 17-24 years of age) were used as embryo and oviductal epithelial cell donors. Embryos (n = 37) were collected from the oviducts 2 days after ovulation and were paired (embryos obtained from young mares with embryos obtained from aged mares) so that eight pairs were co-cultured with young mare oviductal epithelial cells and eight pairs were co-cultured with aged mare oviductal epithelial cells. Five additional embryos obtained from young mares were co-cultured with oviductal epithelial cells from either young mares or aged mares but were not paired. Embryos were co cultured for 7 days at 38.5 degrees C in 5% CO2 or until morphological degeneration was detected. The proportions of paired embryos that reached the blastocyst stage were similar for embryos obtained from young mares and embryos obtained from aged mares after co-culture with oviductal epithelial cells from young mares (6 of 8 versus 5 of 8) or from aged mares (6 of 8 versus 5 of 8), respectively. Although the overall rate of development of embryos to blastocyst from both young mares and aged mares was similar, blastocysts developing from embryos obtained from aged mares were inferior to blastocysts obtained from young mares in terms of number of cell nuclei, quality score, and diameter at day 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861391 TI - Effect of RU486 on ovarian progesterone production at pro-oestrus and during pregnancy: a possible dual regulation of the biosynthesis of progesterone. AB - Changes in progesterone production were analysed after intrabursal ovarian administration of the antiprogesterone RU486, mifepristone, in rats at pro oestrus and during pregnancy. RU486 was administered at 09:00-10:00 h and serum progesterone was measured 8 h after treatment, except for those on days 3 and 12 of pregnancy when the steroid was measured 4, 8 and 24 h later. RU486 stimulates progesterone production on the day of pro-oestrus and on days 3-5 and 15-20 of pregnancy. Conversely, treatment with the antiprogestagen inhibits progesterone production on days 7-14 of gestation. The inhibition (day 12) or stimulation (day 19) of progesterone production induced by RU486 could be correlated with the simultaneous inhibition or stimulation of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity observed in corpora lutea. A similar effect on 3 beta-HSD activity in corpora lutea was obtained by intrabursal ovarian administration of a specific progesterone antibody, indicating that the effect of RU486 is exerted through its antiprogesterone action. On the day of pro-oestrus and during early pregnancy the intrabursal ovarian injection of RU486 did not modify serum prolactin and LH concentrations, demonstrating that the antiprogesterone did not have a central action. The stimulatory action of RU486 on progesterone production on days 3 and 5 of pregnancy shifted to an inhibitory effect on progesterone production on day 7. Oestradiol treatment on day 6 of pregnancy reversed the effect of RU486 on progesterone production on day 7, inducing a response similar to that obtained on days 3 and 5 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861392 TI - Membrane transport properties of mammalian oocytes: a micropipette perfusion technique. AB - A perfusion technique using micropipette methodology was developed to determine quantitatively the membrane transport properties of mammalian oocytes. This method eliminates modelling ambiguities inherent in microdiffusion, a closely related technology, and should prove to be especially valuable for study of the coupled transport of water and cryoprotectant through mammalian oocytes and embryos. The method is described and evidence given for validity of the method for the simple case of uncoupled flow of water through the mouse oocyte membrane. The zona pellucida of a mouse oocyte was held by a micropipette with an 8-10 microns diameter tip opening and perfused by hyperosmotic media. The kinetic volume change of the cell was videotaped and quantified by image analysis. Experimental data and mathematical modelling were used to determine the hydraulic conductivity of the oocyte membrane (Lp) found to be 1.05, 0.45 and 0.26 microns min-1 atm-1 at 30 degrees C, 22 degrees C and 12 degrees C, respectively. The corresponding activation energy, Ea, for Lp was calculated to be 13.0 kcal mol-1. These values are in agreement with data obtained by other techniques. One of the major advantages of this technique is that the extracellular osmotic condition can be changed readily by perfusing a single cell with a prepared medium. To study the response of the same cell to different osmotic conditions, the old perfusion medium can be removed easily and the cell reperfused with a different medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861393 TI - Requirement for testicular macrophages in Leydig cell proliferation and differentiation during prepubertal development in rats. AB - Testicular macrophages in rats were selectively depleted by an intratesticular injection of liposomes containing dichloromethylene diphosphonate into the right testis to study the possible role of these macrophages during the prepubertal development of Leydig cells. The contralateral testes were injected with 0.9% NaCl and served as controls. The animals were injected with the liposomes and NaCl at 5, 10, 15, 20 or 25 days of age. In macrophage-depleted testes, Leydig cell development was inhibited in the animals injected at 5, 10 or 15 days of age. At 35 days of age, the testis was repopulated with macrophages and Leydig cells also developed. Rats treated at 20 or 25 days of age, when Leydig cells were already present in low numbers, did not show any further increases in the number of Leydig cells up to 35 days of age. To study whether the effects of gonadotrophins on Leydig cell development require the presence of macrophages, 21 day-old rats, injected 3 days before with liposomes (right testis) and NaCl (left testis), were treated with 75 iu human FSH kg-1 bodymass day-1, 10 iu hCG per rat day-1, combined hFSH and hCG, or vehicle (PBS with 0.5% BSA) for 6 days. Treatment with hCG induced a sevenfold increase in the number of Leydig cells in the left (macrophage-containing) testis, whereas no increase was found in the right (macrophage-depleted) testis. These results indicate that macrophages are needed for Leydig cell development and for the Leydig cell response to hCG during postnatal maturation. PMID- 7861394 TI - Study of the role of epididymal alpha-glucosidase in the fertility of male rats by the administration of the enzyme inhibitor castanospermine. AB - The activity of epididymal alpha-glucosidase in adult rats was rapidly suppressed to histochemically undetectable levels within 2 days by the continuous release of the enzyme inhibitor castanospermine via a peritoneal osmotic pump at a rate of 100-200 nmol h-1. It was established that mating activities overnight depleted 72% of the spermatozoa in the distal cauda, which was replenished in 2 days, and that fertility began to decline 3 weeks after efferent duct ligation. Male rats of proven mating proficiency and fertility were treated with castanospermine, or buffered saline as control, for up to 30 days and enzyme inhibition was confirmed at the end of treatment by histochemistry. Fertility was normal at the first mating test on day 7, significantly decreased at the second mating on day 9, but recovered in a stepwise manner at subsequent matings on days 12 and 14. Delaying the third mating until day 25 did not sustain the transient subfertility. However, prolonging sperm storage in the distal cauda epididymides and preventing replenishment with freshly matured spermatozoa, by efferent duct ligation for 14 days performed on day 15 during castanospermine administration, caused a decrease in fertility and a change in the kinematics of epididymal spermatozoa of the castanospermine-treated group. In control rats, binding of epididymal spermatozoa to Vicia faba, a lectin specific for glucose and glucosamine, and mannose and mannosamine residues, decreased from the proximal caput to the distal corpus coincident with the increase in alpha-glucosidase activity on the epithelial brush border. Lectin binding then increased in the cauda where enzyme activity was absent. However, castanospermine treatment did not significantly alter this binding profile. The findings suggest that epididymal alpha-glucosidase does not play a crucial role in the development of sperm fertilizing capacity, but may be involved in the preparation of spermatozoa for storage. PMID- 7861395 TI - Enhanced fetal growth in sheep administered progesterone during the first three days of pregnancy. AB - Two experiments were conducted to determine whether administration of progesterone during early pregnancy affects fetal growth in sheep and if any effect is specific to the days of treatment. In the first experiment, Merino ewes were randomly allocated to four treatment groups and inseminated at a synchronized oestrus. Three groups received progesterone on days 1-3, 3-6 or 1-6 of pregnancy while the fourth group was untreated. Concentrations of progesterone in peripheral plasma increased (P < 0.05) in all treatment groups. Fetal growth (to day 74) was greater in all treatment groups than in the control group (P < 0.001) and was greatest when treatments started on day 1. Pregnancy rate was not affected by progesterone treatment on days 3-6, but was reduced (P < 0.05) when treatment began on day 1. In the second experiment, embryos that had been exposed to either a normal (control) or a high concentration of progesterone on days 1-3 were randomly transferred, within groups, to recipient ewes that had or had not been treated with progesterone on days 1-3. In another group, embryos were exposed to a high concentration of progesterone on days 1-3 and the oviducts of the ewe were ligated. An increase in fetal mass was observed in the recipient group that had been treated with progesterone (P < 0.01) but was not observed in the initial group treated with progesterone. A greater fetal mass was also obtained when embryos that had been ligated in the oviducts of ewes treated with progesterone (P < 0.05) were transferred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861396 TI - Presence of the complement-regulatory protein membrane cofactor protein (MCP, CD46) as a membrane-associated product in seminal plasma. AB - The seminal plasma complement regulator membrane cofactor protein (MCP) was examined by sequential centrifugation and phase separation in the detergent Triton X-114. The presence of MCP components in seminal plasma depleted of the 40 kDa sperm MCP product by low speed centrifugation was confirmed. Subsequent centrifugation at 2200 g recovered a pellet containing a prominent 60 kDa and a weak 50-55 kDa MCP component. A 60 kDa MCP product remained detectable in the supernatant fraction after this centrifugation step but this was depleted by ultracentrifugation. Recovery of the seminal plasma MCP components in the pellet fraction obtained by ultracentrifugation suggested that seminal plasma MCP is membrane-associated. Seminal plasma fractions were also subjected to phase separation in Triton X-114. MCP components in both pellet and supernatant fractions partitioned to the detergent phase, confirming that seminal plasma MCP is membrane associated. The origin of these proteins was investigated by analysing MCP products in seminal plasma from vasectomized men. The 40 kDa sperm MCP protein was absent but a 60 kDa MCP component, which partitioned to the detergent phase in Triton X-114, was evident. Seminal plasma therefore contains typical membrane-associated MCP products that appear to be derived distal to the ductus deferens. PMID- 7861397 TI - Effects of Trypanosoma congolense infection in rams on the pulsatile secretion of LH and testosterone and responses to injection of GnRH. AB - Changes in pulsatile secretion of LH and testosterone and responses to exogenous GnRH were assessed at different stages of Trypanosoma congolense infection in rams. Jugular blood samples were collected every 15 min for 6 h followed by immediate injection of GnRH (20 micrograms i.v.) and further sample collection after 10, 20, 40, 60, 80, 100 and 120 min. This sampling and injection regimen was performed 5 days before infection (day -5) and 23 and 52 days after infection. T. congolense infection increased (P < 0.05) the mean plasma LH concentration over 6 h on day 23 (3.2 +/- 0.2 ng ml-1) and decreased (P < 0.05) the mean LH concentration on day 52 (1.2 +/- 0.2 ng ml-1, P < 0.05) compared with day -5 values (2.0 +/- 0.2 ng ml-1). Trypanosome infection induced a rapid decline in plasma testosterone concentration from a mean of 7.5 +/- 1.4 nmol l-1 on day -5 over 6 h to 3.6 +/- 0.4 nmol l-1 (P < 0.05) on day 23 and 1.7 +/- 0.3 nmol l-1 (P < 0.001) on day 52. The observed decline in plasma LH concentration in infected rams was not associated with reduced sensitivity of the pituitary to GnRH or its ability to release LH, as the LH response to exogenous GnRH was not impaired throughout the period of infection. However, the testosterone response to GnRH-induced LH stimulation was depressed on both days 23 and 52 after infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861398 TI - Evidence for the essential role of prostaglandins for parturition in a marsupial, Macropus eugenii. AB - Female tammar wallabies were treated prepartum with the prostaglandin synthase inhibitor indomethacin, with or without the dopamine agonist bromocriptine, to suppress the peripartum pulses of plasma prostaglandin and prolactin. The animals were observed continuously to detect birth, and a series of blood samples taken to define the hormonal profiles before and immediately after parturition. Birth was observed in ten of twelve control animals but not in the six animals treated with indomethacin alone or the six animals treated with indomethacin and bromocriptine. Indomethacin disrupted the normal profile of PGF2 alpha metabolite 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) concentrations, and in the females treated with bromocriptine plus indomethacin the pulse of prolactin normally seen at parturition was completely abolished. Plasma progesterone concentrations fell slowly in treated animals, whereas in control animals they fell steeply immediately after parturition. Postpartum oestrus was delayed or absent in treated and most control animals, suggesting that the frequent blood sampling and disturbances in the peripartum period interfered with these endocrine processes. We conclude that prostaglandin is essential for normal birth. Prolactin, in the apparent absence of a prostaglandin peak, does not induce birth or rapid luteolysis. Prostaglandin release may synchronize the rapid fall in progesterone concentrations associated with birth, but in the absence of this signal, the corpus luteum undergoes a less rapid, autonomous decline. PMID- 7861399 TI - Significance of changes in fetal perfusion pressure to factors controlling angiogenesis in the human term placenta. AB - The objective of the study was to determine the effects of mechanical factors on endothelial proliferation in the human placental villous vasculature. Individual fetal lobules were perfused with tissue culture medium at two different standard pressures (40 and 100 mm Hg). The perfused area was then removed and diced into small blocks which were quench frozen in liquid nitrogen. Cryostat sections were obtained and fixed in acetone at 4 degrees C. Proliferating cell nuclear antigen was then identified using Ki67 antibody as a marker. Proliferating nuclei were scored, using a light microscope, and a comparison made between the two pressures used. More proliferating endothelial nuclei were found at 100 mm Hg than at 40 mm Hg (P < 0.05). It is therefore concluded that mechanical factors may play a role in villous angiogenesis and the formation of terminal villi. PMID- 7861400 TI - Influence of paced mating and number of intromissions on fertility in the laboratory rat. AB - The effects of differential mating stimulation on fertility in rats were examined by mating pro-oestrous females for one ejaculatory series in tests in which they could or could not self-regulate, or pace, the timing of intromissions received by males. Females were autopsied on days 7, 14 or 21 after mating, or on the expected day of birth to confirm pregnancy, and the number of implantation sites or of viable fetuses or pups determined. Because of substantial behavioural variability within an ejaculatory series, data from paced and nonpaced females were divided according to whether they received a low (< or = 8) or high (> or = 9) number of intromissions. The incidence of pregnancy was significantly reduced among paced females receiving few intromissions relative to that of any other group. Histological examination of ovaries from females autopsied on day 7 after mating suggested that the reduced pregnancy rate among this paced, low intromission group resulted from a failure of activation of the corpora lutea, a possible consequence of the low number of intromissions received by these females. However, in paced, low intromission females that became pregnant, litter size was significantly greater than in nonpaced, low intromission females. These results suggest a compensatory effect of the temporal patterning of intromissive stimulation on fertility. This effect is not a consequence of differential mortality after implantation since there was no difference in litter size among females autopsied at any of the four times. The differences between paced and nonpaced females may be attributable to preimplantation effects such as differential release of ova or sperm transport. PMID- 7861401 TI - Acceleration and deceleration of sexual maturation by social cues in a tropical rodent Zygodontomys brevicauda. AB - The effects of social cues from adult conspecifics on the rate of sexual maturity were studied in a tropical rodent, the cane mouse (Zygodontomys brevicauda), in the laboratory. Several aspects of the biology of this species have suggested that it might be atypical in that young females may not accelerate or decelerate their rate of reproductive development in response to social cues. This hypothesis was tested by housing 16-day-old females with an adult male, an adult female, or alone, and reproductive development was assessed periodically, beginning when the mice were 20 days old. Young females paired with males underwent more uterine growth and matured markedly earlier than did isolated controls. Young females paired with adult females exhibited less uterine growth than did isolated controls. Thus, social cues both accelerate and decelerate reproductive development in females of this species, and the hypothesis that social cues have no effect on reproductive development in young females was rejected. The evolutionary conditions that favour unresponsiveness of young females to social cues appear to be restrictive, and may be rare in mammals. PMID- 7861402 TI - Follicular and hormonal development in prepubertal heifers from 2 to 36 weeks of age. AB - The aim of this study was to characterize changes in ovarian follicle dynamics in relation to changes in hormone secretion in heifer calves from birth to 8 months of age. The position and diameter of ovarian follicles > or = 4 mm in diameter were recorded, the number of ovarian follicles > or = 2 mm in diameter counted, and blood samples collected daily for periods of 18 days, starting at 2, 8, 14, 24 and 34 weeks of age in ten heifers. The mean age at first ovulation was 52.8 +/- 1.6 weeks. At all ages ovarian follicular development occurred in a wave-like manner, as in mature cattle. The maximum diameter of the dominant and the largest subordinate follicles increased between 2 and 34 weeks of age (P < 0.05); however, the greatest increase occurred between 2 and 8 weeks of age. There was a similar increase in the numbers of small and large ovarian follicles (P < 0.05). The duration of detection of dominant follicles (number of days visible at a diameter of > or = 4 mm) also increased between 2 and 34 weeks of age (P < 0.05). The emergence of waves of follicular development was preceded by peaks in plasma FSH concentrations (P < 0.05) at 2 weeks of age but this was less clear at other ages. There was a rise in circulating concentrations of gonadotrophins between 4 and 14 weeks of age. We concluded that in heifer calves as young as 2 weeks of age ovarian follicles grew in a wave-like fashion, similar to those of adult cattle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861403 TI - Molecular mass and isoelectric properties of pituitary and urinary gonadotrophins in callitrichid primates. AB - In this study, the molecular masses and isoelectric characteristics of pituitary LH and FSH in two species of callitrichid primate, the common marmoset (Callithrix jacchus) and the cotton-top tamarin (Saguinus oedipus), were determined. Comparative data for urine samples from Callithrix jacchus are also presented. The separation of gonadotrophins from pituitary extracts and urine was performed under nonreducing conditions using SDS-PAGE and isoelectric focusing procedures. Hormone activity in gel eluates was determined by in vitro bioassays for LH and FSH and by a microtitre plate enzymeimmunoassay for LH. The molecular masses of pituitary and urinary proteins were between 36 and 37 kDa for LH and FSH, and were similar in both species. A dimer form of pituitary LH with a molecular mass of 33 kDa was also found in the cotton-top tamarin, but not in the marmoset. Guanidine-HCl dissociation of gonadotrophins from marmoset and tamarin pituitaries before electrophoresis gave proteins of 16 and 28 kDa, and 16 and 25 kDa range, respectively. Isoelectric focusing revealed numerous peaks of bioactivity for both LH and FSH, indicating the presence of multiple molecular variants (isoforms) of each hormone. In both species pituitary FSH eluted over a narrower and more acidic pH range than LH. Isoelectric focusing profiles for pituitary and urinary LH in the marmoset were similar (pH range 5.0-8.5), whereas urinary FSH demonstrated a more acidic profile than the pituitary protein. These results give comparative information on the properties of New World primate gonadotrophins, which should be useful in studies of their physiological action and in aiding the development of improved reagents and assays for their detection. PMID- 7861404 TI - Inhibitors of HIV-1 protease containing the novel and potent (R) (hydroxyethyl)sulfonamide isostere. PMID- 7861405 TI - Highly kappa receptor-selective dynorphin A analogues with modifications in position 3 of dynorphin A(1-11)-NH2. PMID- 7861406 TI - IAM chromatography: an in vitro screen for predicting drug membrane permeability. AB - Fluid cell membranes are the main barrier to drug absorption when diffusion limits uptake. Immobilized artificial membranes (IAMs) are solid phase models of fluid membranes that predicted oral drug absorption in mice for a homologous set of cephalosporins. IAMs also predicted drug permeability through Caco-2 cells. Since drug permeability in Caco-2 cells is known to correlate with the oral absorption of drugs in humans, IAMs may also model drug absorption in humans. IAM analysis is experimentally simple, and large-volume screening of experimental compounds for drug absorption is possible. PMID- 7861407 TI - Synthesis and structure-activity relationships of dequalinium analogues as K+ channel blockers. Investigations on the role of the charged heterocycle. AB - Small conductance Ca(2+)-activated K+ (SKCa) channels occur in many cells but have been relatively little studied. Dequalinium, a bis-quinolinium compound, has recently been shown to be the most potent nonpeptidic blocker of this K+ channel subtype. This paper examines the importance of the quinolinium rings for blocking activity. Analogues of dequalinium were synthesised in which one quinolinium group was removed (1 and 2) or replaced by a triethylammonium group (3). They have been assayed in vitro for their ability to block the after-hyperpolarization (mediated by the opening of SKCa channels) that follows the action potential in rat sympathetic neurones. The compound having one quinolinium and one triethylammonium group (3) showed reduced activity, and it is suggested that the stronger binding to the channel of the quinolinium relative to the triethylammonium group may be related to differences in their electrostatic potential energy maps. Two monoquaternary compounds (1 and 2) were tested, but they exhibited a different pharmacological profile that did not allow definite conclusions to be drawn concerning their potency as blockers of the SKCa channel. Replacement of both quinolinium groups by pyridinium, acridinium, isoquinolinium, or benzimidazolium reduced but did not abolish activity. These results show that compounds having a number of different heterocyclic cations are capable of blocking the SKCa channel. However, among the heterocycles studied, quinoline is optimal. Furthermore, charge delocalization seems to be important: the higher the degree of delocalization the more potent the compound. PMID- 7861408 TI - Structure-activity relationships of lactone ring-opened analogs of the antimalarial 1,2,4-trioxane artemisinin. AB - 1,2,4-Trioxane benzylic ethers 8a-e were prepared as simplified, tricyclic versions of the clinically used tetracyclic antimalarial drug artemisinin (1). Five additional artemisinin analogs (9-11) were prepared. Neither water solubility (analogs 8e and 11b) nor chelating ability (analogs 9 and 10), however, produced trioxanes of especially high in vitro antimalarial activity. Trioxane fluorobenzyl ether 8b is the most active in this series (more active than artemisinin) against Plasmodium falciparum parasites in vitro, with substantial activity also in mice infected with Plasmodium berghei parasites and with 10 times higher activity than artemisinin (1) in killing immature P. falciparum gametocytes. PMID- 7861409 TI - Synthesis and antimalarial activities of 12 beta-allyldeoxoartemisinin and its derivatives. AB - Synthesis of 12 beta-allyldeoxoartemisinin from dihydroartemisinin and subsequent transformations to other 12 beta-alkyldeoxoartemisinins are described. All compounds were tested in vitro versus two drug-resistant strains (Plasmodium falciparum) of malaria. The in vivo activity and toxicity of the most active compound, 12 beta-propyldeoxoartemisinin, were comparable to that of arteether. PMID- 7861410 TI - Studies on new acidic azoles as glucose-lowering agents in obese, diabetic db/db mice. AB - Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles, isoxazol-3- and -5-ones and a pyrazol-3-one, showed significant plasma glucose-lowering activity (17-42% reduction) in genetically obese, diabetic db/db mice at a dose of 100 mg/kg/day x4. Structure activity relationship studies determined that 5-alkyl-4-(arylmethyl)pyrazol-3 ones, which exist in solution as aromatic enol/iminol tautomers, were the most promising new class of potential antidiabetic agent (32-45% reduction at 20 mg/kg/d x4). Included in this work are convenient syntheses for several types of acidic azoles that may find use as new acidic bioisosteres in medicinal chemistry such as the antidiabetic lead 5-(trifluoromethyl)pyrazol-3-one (hydroxy tautomer) and aza homologs of the pyrazolones, 1,2,3-triazol-5-ones (hydroxy tautomer) and 1,2,3,4-tetrazol-5-one heterocycles. log P and pKa data for 15 potential acidic bioisosteres, all appended to a 2-naphthalenylmethyl residue so as to maintain a similar distance between the acidic hydrogen and arene nucleus, are presented. This new data set allows comparison of a wide variety of potential acid mimetics (pKa 3.78-10.66; log P -0.21 to 2.76) for future drug design. PMID- 7861411 TI - Molecular similarity matrices and quantitative structure-activity relationships: a case study with methodological implications. AB - Recently, statistical analysis of molecular similarity matrices has been applied to the quantitative structure-activity relationship (QSAR) analysis of a number of molecular series. This paper addresses a number of methodological issues relative to the similarity matrices. A series of halogenated aliphatic hydrocarbons, for which the mutation (aneuploidy) induction ability had previously been determined, was used as test bench. The chemical information carried by the similarity matrices was shown to overlap to a considerable extent the information carried by the classical descriptors (physical chemical and quantum mechanical parameters). A good QSAR was obtained on the basis of the similarity matrices, in analogy with that obtained with the classical descriptors; however, the similarity matrices neither complemented the classical descriptors nor were able to improve on their performance. The effect of the compound's spatial orientation on the similarity values was also investigated. PMID- 7861412 TI - Polyiodinated triglyceride analogs as potential computed tomography imaging agents for the liver. AB - A series of glyceryl 2-oleoyl 1,3-bis[omega-(3-amino-2,4,6-triiodophenyl)] alkanoates was synthesized, radioiodinated with iodine-125, emulsified, and evaluated for their ability to selectively localize in the liver for potential use as hepatographic agents in computed tomography. All seven analogs displayed rapid liver uptake wherein between 65 and 78% of the injected dose accumulated in the liver by 30 min. Liver values ranged from 46 to 93% 3 h after injection which corresponded to liver to blood ratios ranging from 21 to 450. Moreover, subsequent elimination of radioactivity from the liver was nearly linear with respect to alkyl chain length. Analogs with longer alkyl chain length were eliminated from the liver more rapidly than their shorter chain counterparts. Because of their biochemical similarities to naturally occurring triglycerides, these novel analogs may prove useful not only for high-resolution anatomic imaging of focal liver lesions, but also for evaluating a variety of diffuse diseases known to affect hepatic function and biochemistry. PMID- 7861413 TI - (R)-11-hydroxy- and (R)-11-hydroxy-10-methylaporphine: synthesis, pharmacology, and modeling of D2A and 5-HT1A receptor interactions. AB - (R)-11-Hydroxyaporphine (2) and (R)-11-hydroxy-10-methylaporphine (3) were synthesized from natural morphine by using new, short, and efficient synthetic sequences. The dopaminergic and serotonergic effects of 2 and 3 were evaluated by use of in vitro and in vivo test systems. The results indicate that 3 is a potent, selective, and efficacious 5-HT1A receptor agonist. In contrast, 2 is a partial 5-HT1A receptor agonist of low potency which has affinity also for central D1 and D2A receptors. The differences in pharmacological profiles were rationalized by modeling of ligand-receptor interactions using homology-based receptor models of the 5-HT1A and D2A receptor binding site. The selective and pronounced serotonergic effects of 3 appear to be due to the C10-methyl group, which is accommodated by a lipophilic pocket in the 5-HT1A receptor. In contrast, the C10-methyl group of 3 is not accommodated by the binding site model of the D2A receptor. PMID- 7861414 TI - Three-dimensional quantitative structure-activity relationships of sulfonamide endothelin inhibitors. AB - A three-dimensional quantitative structure-activity relationship (QSAR) using steric and electrostatic fields (comparative molecular field analysis, CoMFA) applied to 36 aryl sulfonamides assayed for endothelin receptor subtype-A (ETA) antagonism provided high cross-validation correlations (0.7) and showed promising predictive ability. The results were validated through trials using scrambled activities as well as trials using scrambled orientation of molecules. CoMFA was used to discriminate between alternate hypothetical biologically active conformations. CoMFA was also used to discriminate between two different molecular superpositions representing possible positioning within the receptor binding site. The preferred superposition supports hypotheses that suggest Tyr129 in the ETA receptor as a key residue for antagonist binding. Significant CoMFA results were obtained when crudely optimized geometries and simple charge schemes were used. The results improved on refinement, most substantially with refinement of the atomic charges. PMID- 7861415 TI - Synthesis, structure-activity relationships, and pharmacological evaluation of pyrrolo[3,2,1-ij]quinoline derivatives: potent histamine and platelet activating factor antagonism and 5-lipoxygenase inhibitory properties. Potential therapeutic application in asthma. AB - A series of pyrrolo[3,2,1-ij]quinoline derivatives was synthesized and evaluated for their in vitro and in vivo activities against histamine, platelet activating factor (PAF), and leukotrienes which are recognized to be of importance in asthma. The structure-activity relationship studies have shown that the optimum moiety on the 1-position of the pyrroloquinoline nucleus is a 2-[4-(4-methyl-2 pyridinyl)-1-piperazinyl]ethyl chain in conjunction with a methyl group on the 2 position for potent antagonism of both histamine and PAF. The introduction of substituents on the 8- and 4-positions was also investigated in order to increase the potency of 5-lipoxygenase inhibition while retaining or improving the activities against histamine and PAF. This series is exemplified by 4-n-butyl-5,6 dihydro-8-hydroxy-2-methyl-1- [2-[4-(4-methyl-2-pyridinyl)-1-piperazinyl]ethyl] 4H-pyrrolo[3,2,1- ij]quinoline (24, KC 11404) which was found to be active against all three of the selected mediators. Compound 24 was found to be orally active in guinea pig models against the histaminic phase of antigen-induced bronchospasm and PAF-induced bronchoconstriction (ED50 = 1.9 and 2.1 mumol/kg, respectively). When tested against the leukotriene-dependent phase of the antigen induced bronchoconstriction, compound 24 showed the same potency as zileuton. PMID- 7861416 TI - Dual-acting thromboxane receptor antagonist/synthase inhibitors: synthesis and biological properties of [2-substituted-4-(3-pyridyl)-1,3-dioxan-5-yl] alkenoic acids. AB - The design, synthesis, and pharmacology of a new class of compounds possessing both thromboxane receptor antagonist and thromboxane synthase inhibitory properties are described. Replacement of the phenol group of the known thromboxane antagonist series 4(Z)-6-[(4RS,5SR)-4-(2-hydroxyphenyl)-1,3-dioxan-5 yl] hex-4-enoic acid by a 3-pyridyl group led to a series of compounds, 5, which were potent thromboxane synthase inhibitors and weak thromboxane antagonists. Further modifications at the dioxane C2 position led to compounds, 7, which were potent dual-acting agents. In the case of compound 7w, the dual activity was shown to reside almost exclusively in the (-)-enantiomer, 7x. Following oral dosing to rats and dogs, 7x (3 mg/kg) displayed significant dual activity over a period of at least 8 h. PMID- 7861417 TI - Synthesis and structure-activity relationships of oxamic acid and acetic acid derivatives related to L-thyronine. AB - Aryloxamic acids 7 and 23, (arylamino)acetic acids 29, arylpropionic acids 33, arylthioacetic acids 37, and (aryloxy)acetic acid 41 related to L triiodothyronine (L-T3) were prepared and tested in vitro for binding to the rat liver nuclear L-T3 receptor and the rat membrane L-T3 receptor. The structure activity relationships for these compounds are described, with 7f, 23a, 29c, 33a, 37b, and 41 showing excellent potency (IC50's of 0.19, 0.16, 1.1, 0.11, 3.5, and 0.10 nM, respectively) to the nuclear receptor and significantly lower binding affinity to the membrane receptor (IC50's > 5 microM). Some of these compounds, especially in the oxamic acid series 7 and 23, showed an unprecedented potency for methyl-substituted derivatives such as 7f and 23a. Compounds 7f and 23a showed good lipid lowering effects in rats with ED50's of 20 and 5 micrograms/kg po, respectively, and a lack of cardiac side effects in rats at doses as high as 10 and 25 mg/kg po, respectively. PMID- 7861418 TI - Binding of 5H-dibenzo[a,d]cycloheptene and dibenz[b,f]oxepin analogues of clozapine to dopamine and serotonin receptors. AB - Series of 5,11-dicarbo- and 11-carbo-5-oxy-10-(1-alkyl-1,2,3,6-tetrahydro-4 pyridinyl) analogues and a 11-carbo-5-oxy-10-(1-methyl-4-piperidinyl) analogue of the atypical antipsychotic agent clozapine were prepared and tested for binding to the dopamine D-2L and D-4 and serotonin S-2A and S-2C receptors. Some of these analogues were found to have dopamine D-2L and D-4 and serotonin S-2A and S-2C receptor binding activities as high as or higher than those of clozapine, indicating that neither the diazepine structure nor the piperazine ring present in clozapine is essential for high antidopamine activity and or for high dopamine D-4 selectivity (Ki for the dopamine D-2L receptor/Ki for the dopamine D-4 receptor). Increasing in the effective size of the alkyl substituent at the tertiary amine nitrogen atom in the 1,2,3,6-tetrahydro-4-pyridinyl moiety in the 5H-dibenzo[a,d]cycloheptene series reduces the affinity for the dopamine D-4 receptor, but in the dibenz[b,f]oxepin series, no significant change in binding affinity to the dopamine D-4 receptor was observed. Equal or slightly higher affinity for the serotonin S-2A and S-2C receptors was observed for the 10-(1 ethyl-1,2,3,6-tetrahydro-4- pyridinyl) analogues in both series, but for the 10 [1,2,3,6-tetrahydro-1-(2-propenyl)-4- pyridinyl] analogues, any favourable steric factor is overshadowed by an unfavorable electronic effect as a result of change in the basicity of the tertiary amino group in the pyridinyl moiety. Replacement of three of the four nitrogen atoms in clozapine with three carbon or two carbon atoms and an oxygen atom and removal of the chlorine atoms gives 10-(1,2,3,6 tetrahydro-1- methyl-4-pyridinyl)dibenzo[a,d]cycloheptene and 10-(1-methyl-4 piperidinyl)dibenz[b,f]oxepin, each having twice the binding activity to the dopamine D-4 receptor as does clozapine and a dopamine D-4 selectivity equal to that of clozapine. PMID- 7861419 TI - Prediction of receptor properties and binding affinity of ligands to benzodiazepine/GABAA receptors using artificial neural networks. AB - To date the use of artificial neural networks (ANNs) in quantitative structure activity relationship (QSAR) studies has been primarily concerned in comparing the predictive accuracy of the technique using known data sets where the data set parameters had been preselected and optimized for use with other statistical methods. Little effort has been directed at optimizing the input parameters for use with ANNs or exploring other potential strengths of ANNs. In this study, back propagation ANNs and multilinear regression (MLR) were used to examine the QSAR between substituent constants and random noise at six positions on 57 1,4 benzodiazepin-2-ones (1,4-BZs) and their binding affinities (log IC50) for benzodiazepine GABAA receptor preparations. By using selective pruning and cross validation techniques, it was found possible to use ANNs to indicate an optimum set of 10 input parameters from a choice of 48 which were then used to train back propagation ANNs that best predicted the receptor binding affinity with a high correlation between known and predicted data sets. Using the optimum set of input parameters, three-layer ANNs performed no better than the two-layer ANNs which gave marginally better results than MLR. Using the trained ANNs to examine the individual parameters showed that increases in the lipophilicity and F polar value at position 7, F polar value at position 2', and dipole at position 1 on the molecule all enhanced receptor binding affinity of 1,4-BZ ligands. Increases in molar refractivity and resonance parameters at position 1, molar refractivity at positions 6' and 2', Hammet meta constant at position 3', and Hammet para constant at position 8 on the molecule all caused decreases in receptor binding affinity. By considering the optimal ANNs as pharmacophore models representing the internal physicochemical structure of the receptor site, it was found that they could be used to critically examine the properties of the receptor site. PMID- 7861420 TI - C-9 and N-substituted analogs of cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3- propyl 1H-benz[e]indole-9-carboxamide: 5-HT1A receptor agonists with various degrees of metabolic stability. AB - Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-) 2,3,3a,4,5,9b-hexahydro-3-propyl-1H-benz[e]indole-9- carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R2) were synthesized, and their serotonergic activity was evaluated in vitro and in vivo. Many of these compounds were incubated in the presence of rat hepatocytes, and the metabolic stability in vitro was compared to that of compound 1. Only the N-methyl and N-ethyl analogs ((-)-5a and (-)-5b) were more stable than compound 1, indicating that N-dealkylation is a major route of metabolism in this series. In addition, these analogs were found to be partial 5-HT1A receptor agonists in vivo. Modifications were also made to the carboxamide functionality of compound 1 (R1 in 2) to yield substituted amides or ketones. Among these analogs, the methyl ketone (-)-15a was found to be a 5-HT1A agonist with full intrinsic activity in vivo and was approximately 20 times more potent than compound 1 and 5 times more potent than 8-OH-DPAT. PMID- 7861421 TI - Isolation and characterization of a cyclic hydroxamic acid from a pollen extract, which inhibits cancerous cell growth in vitro. AB - One fraction, designated FV-7, in the water soluble ingredient of the pollen extract Cernilton was found to be inhibitory to the growth of a prostate cancer cell line. Characterization of FV-7 by high-resolution mass spectrometry and nuclear magnetic resonance identified the fraction as hydroxamic acid, 2,4 dihydroxy-2H-1,4-benzoxazin-3(4H)-one (DIBOA). To confirm this further, we synthesized an authentic sample of DIBOA and found subsequently that the synthetic DIBOA was structurally indistinguishable from FV-7. Furthermore, in a separate experiment we compared the in vitro effects of FV-7 and DIBOA on the growth of a prostate cancer cell line and found that in both cases the effect was inhibitory and that the inhibition curves obtained for both compounds were virtually identical. PMID- 7861422 TI - Withholding and withdrawing life-prolonging treatment--moral implications of a thought experiment. PMID- 7861423 TI - Children's informed consent to treatment: is the law an ass? PMID- 7861424 TI - Ethics in scientific communication: study of a problem case. AB - The hypothermia experiments performed on humans during the Second World War at the German concentration camp in Dachau have been regarded as crimes against humanity, disguised as medical research. For almost 50 years, scientists maintained that the study produced valuable, even if not totally reliable, information. In recent years, the results from the Dachau hypothermia project were glamorized with life-saving potential and a heated ethical dialogue was activated about the use of life-saving but tainted scientific information. In the wake of the debate, an in-depth examination of the scientific rigour of the project was performed and revealed that neither the science nor the scientists from Dachau could be trusted and that the data were worthless. The body of medical opinion accepted the unfavourable determination but a few scientists and ethicists have continued to endorse the validity, of at least parts, of the Dachau hypothermia data. The conduct of the scientific communications about the Dachau hypothermia experiments by the scientific and ethical communities invites serious consideration of a possible ethical misadventure. It appears that for almost 50 years, the results of the study had been endorsed without careful examination of the scientific base of the experiments and that secondary citation of relevant original material may have been commonly employed. These infractions contributed to a myth that good science was practised by the Nazis at Dachau. The more recent emphasis on the life-saving potential of the Dachau data, without citation of credible supporting evidence, has also been misleading. Similarly, acceptance of a determination by an in-depth examination that the 'whole' Dachau project if flawed with simultaneous endorsement of the validity of 'parts' of the results, poses an ethical problem. It is advisable that before seeking ethical consultation about the use of unethically obtained data, scientists should examine the quality of science behind the controversial information and ethicists should verify the integrity of the material prior to engaging in a dialogue. PMID- 7861425 TI - Euthanasia in Holland: an ethical critique of the new law. AB - In the Netherlands the government's proposal for the legal regulation of euthanasia, assisted suicide and the termination of a patient's life without request has been approved by Parliament. The defence of this proposal is to a large extent based on a specific interpretation of data about the practice of euthanasia in that country, published in 1991 (the Remmelink Report). This paper discusses both the interpretation of the data and the new law. On the basis of that and other data, the author concludes that many cases of euthanasia, assisted suicide and termination of a patient's life without request remain unnotified and therefore unreviewed by the legal authorities. It is argued that the new law will not guarantee an improvement to this situation. In short, the new law will not protect effectively the lives of patients, and must, therefore, be open to ethical and legal objection. PMID- 7861426 TI - Are withholding and withdrawing therapy always morally equivalent? AB - Many medical ethicists accept the thesis that there is no moral difference between withholding and withdrawing life-sustaining therapy. In this paper, we offer an interesting counterexample which shows that this thesis is not always true. Withholding is distinguished from withdrawing by the simple fact that therapy must have already been initiated in order to speak coherently about withdrawal. Provided that there is a genuine need and that therapy is biomedically effective, the historical fact that therapy has been initiated entails a claim to continue therapy that cannot be attributed to patients who have not yet received therapy. This intrinsic difference between withholding and withdrawing therapy is of moral importance. In many instances, patients will waive this claim. But when one considers withdrawing therapy from one patient to help another in a setting of scarce resources, this intrinsic moral difference comes into sharp focus. In an era of shrinking medical resources, this difference cannot be ignored. PMID- 7861427 TI - Research on leukaemia cells surplus to diagnostic needs in children. AB - The ability to improve diagnosis and refine prognosis in children with acute leukaemia is improving steadily. A growing number of tests can and are being performed on leukaemic cells. These include surface-marker analysis, DNA content, cytogenetics and studies of gene rearrangements. Increasingly large bone-marrow samples, now usually obtained under general anaesthesia, are required to make secure diagnoses. Ethical issues arise from three major areas. 1) Current research on leukaemia cells requested by the Medical Research Council is considered by local research ethics committees, but parents are not regularly given detailed information about or asked specifically to consent to such research; 2) substantial quantities of excess cells are stored indefinitely. This archive of stored material is a valuable resource for research but there has been little consideration of the ethical issues which arise from this practice, and 3) there is a potential for pressure to obtain increasingly large samples. 'Creeping growth' in sample size is likely to continue unless ethics committees consider future research proposals in more detail. These issues deserve attention in order that worthwhile research and its publication are not impeded for want of ethical consideration. The implications extend beyond the field of childhood leukaemia. PMID- 7861428 TI - The Oxford Practice Skills Project: teaching ethics, law and communication skills to clinical medical students. AB - We describe the teaching programme in ethics, law and communication skills for clinical medical students which is being developed as part of the Oxford Practice Skills Project. These three elements of practice are approached in an integrated teaching programme which aims to address everyday clinical practice. The role of a central value of patient-centred health care in guiding the teaching is described. Although the final aim of the teaching is to improve actual practice, we have found three 'sub-aims' helpful in the development of the programme. These sub-aims are: increasing students' awareness of ethical issues; enhancing their analytical thinking skills, and teaching specific knowledge. PMID- 7861429 TI - Teaching ethics in the context of the medical humanities. PMID- 7861430 TI - The teaching of medical ethics to medical students. AB - Teaching medical ethics to medical students in a pluralistic society is a challenging task. Teachers of ethics have obligations not just to teach the subject matter but to help create an academic environment in which well motivated students have reinforcement of their inherent good qualities. Emphasis should be placed on the ethical aspects of daily medical practice and not just on the dramatic dilemmas raised by modern technology. Interdisciplinary teaching should be encouraged and teaching should span the entire duration of medical studies. Attention should be paid particularly to ethical problems faced by the students themselves, preferably at the time when the problems are most on the students' minds. A high level of academic demands, including critical examination of students' progress is recommended. Finally, personal humility on the part of teachers can help set a good example for students to follow. PMID- 7861431 TI - Patient involvement in clinical teaching. AB - This paper presents findings from a longitudinal study of patient refusals (as reported by graduating medical students) to take part in the teaching function of public hospitals. Results from a smaller study of non-patients' attitudes are also reported. Findings are discussed in terms of patients' rights, issues of personal privacy, medical education, and the public good. PMID- 7861432 TI - Genetic counselling. PMID- 7861433 TI - The ethics of paid versus volunteer blood donation. PMID- 7861434 TI - Drug trial ethics. PMID- 7861435 TI - In defence of ageism. PMID- 7861436 TI - Lifestyles and allocation of health care resources. PMID- 7861437 TI - Chagas' disease: a case in south Mississippi. AB - Chagas' Disease is common in Central and South America. As the number of immigrants increase in the United States and North America the incidence of Chagas' Disease is increasing. This is a report of chronic Chagas' Disease diagnosed on the Gulf Coast. A review of the recent literature suggests seropositivity in the United States to be approximately 350,000 people with approximately 100,000 cases of chronic Chagas' Disease. The triad of cardiomegaly, megaesophagus, and mental disease are common symptoms. A case report, literature review, epidemiology, and diagnostic studies are presented. PMID- 7861438 TI - Mississippi physician supply--shortage? Or surplus? PMID- 7861439 TI - Case records of the Department of Medicine University of Mississippi Medical Center: polyarteritis nodosa. PMID- 7861440 TI - Cytokines and metabolic dysfunction after severe head injury. AB - Patients with head injury must overcome central as well as peripheral metabolic insults. In addition to specific tissue damage to the brain, a cellular biochemical cascade occurs that can negatively affect organ function, cause a systemic response to injury, and may cause secondary tissue injury. The metabolites involved in this cascade are numerous and complex. Cytokines are important cell-to-cell communication mediators during injury. It is speculated that cytokines, such as interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF), and interleukin 8 (IL-8), which are found in elevated amounts in both human and basic trials after head injury, play a role in the cellular cascade of injury. Some of the metabolic events produced by small doses of cytokine infusion in animals, as well as humans, include fever, neutrophilia, muscle breakdown, altered amino acid metabolism, depression of serum zinc levels, production of hepatic acute phase reactants, increased endothelial permeability, and expression of endothelial adhesion molecules. These are all known sequelae of severe head injury. Cytokines have also been implicated in organ failure. Infusion of cytokines in basic science trials revealed that organ functions of the gut, liver, and lung are negatively altered by high-dose cytokine infusion. Infusion of certain cytokines has been shown to cause death of brain cells, increase blood-brain barrier permeability, and cause cerebral edema. This suggests that cytokines may also play a role in the sequelae of organ demise. These effects of cytokines have been attenuated in basic trials by blocking the initial signaling system of cytokines or by decreasing serum cytokine activity. We hypothesize that cytokines that are elevated after head injury play a role in the pathology of injury, including altered metabolism and organ demise. PMID- 7861441 TI - Nerve growth factor in CNS repair. AB - The hypothesis that neurotrophic factors play important roles in the adult central nervous system (CNS) has been successfully investigated in the past decade with regard to experimental and pathologic situations. Trophic roles in adult CNS axonal regeneration, on the other hand, have received much less attention. We review three groups of recent studies that demonstrate the relevance of nerve growth factor (NGF) for the regeneration of selected axons into adult central nervous tissue. The first group concerns a septohippocampal model where transected septal cholinergic axons are allowed to regrow into the hippocampal formation through a peripheral nerve bridge implanted into the transection lesion gap. NGF is required in the bridge, enhances penetration of the hippocampal tissue when infused there, and both attracts and promotes sprouting within the septum when infused in the lateral ventricle or the septal tissue itself. The second group of studies concerns the development of a spinal cord sensory regeneration model, where dorsal root ganglionic axons regrow into a nerve bridge placed within the dorsal spinal cord. Preliminary data indicate that NGF infusion rostral to the bridge once again promotes substantial penetration of the adult cord tissue by the regenerating NGF-sensitive fibers. In the third group of studies, attention has been shifted to the location of endogenous NGF in the adult rat hippocampal formation and the normal or lesion-induced occurrence of extrasomal NGF immunoreactivity. These regions of anchored NGF have the ability to attract NGF-sensitive growing axons and may provide opportunities to investigate local cues for final definition of terminal fields. PMID- 7861442 TI - Different cerebral hemodynamic responses following fluid percussion brain injury in the newborn and juvenile pig. AB - The present study was designed to characterize the influence of early developmental changes on the relationship among systemic arterial pressure, cerebral hemodynamics, and cerebral oxygenation during the first 3 h following percussion brain injury. Anesthetized newborn (1-5 days old) and juvenile (3-4 weeks old) pigs equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. Brain injury of moderate severity (1.9-2.3 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Mean arterial blood pressure increased after brain injury in juveniles (68 +/- 4 to 93 +/- 2 mm Hg within 3 min, n = 6), whereas it decreased after injury in newborns (70 +/- 3 to 51 +/- 3 mm Hg within 3 min, n = 6). Fluid percussion brain injury decreased pial artery diameter more in newborns (132 +/- 5 to 110 +/- 5 microns within 10 min, n = 5) than in juveniles (141 +/- 3 to 133 +/- 3 microns within 10 min, n = 5). Pial arterioles constricted to a greater extent than small pial arteries following brain injury in both age groups. Within 30 sec, brain injury produced a transient increase in cerebral hemoglobin O2 saturation (27 +/- 4%, n = 5) that was reversed to a profound decrease in cerebral hemoglobin O2 saturation (45 +/- 2%, n = 5) in the newborn as measured by near infrared spectroscopy. In contrast, brain injury produced modest increases in hemoglobin O2 saturation (10 +/- 1%, n = 5), followed by mild desaturation (4 +/- 1%, n = 5) in juveniles. Additionally, regional cerebral blood flow was reduced within 10 min of injury in both newborn and juvenile pigs and remained depressed for 180 min in newborns. In contrast, cerebral blood flow returned to control values within 180 min in juveniles. These data show that the effects of comparable brain injury level were very different in newborn and juvenile pigs. Further, these data suggest that reductions in cerebral blood flow following brain injury are more dependent on changes in reactivity of arterioles. Finally, these data suggest that the decrease in cerebral oxygenation, an index of metabolism, coupled with reduced cerebral blood flow, could result in profound hypoperfusion after brain injury. PMID- 7861443 TI - Neutrophil accumulation after traumatic brain injury in rats: comparison of weight drop and controlled cortical impact models. AB - Previous work in our laboratory and others using the weight drop (WD) model of traumatic brain injury (TBI) has shown that neutrophils accumulate in brain tissue during the initial 24 h posttrauma as measured by myeloperoxidase (MPO) activity and immunohistochemistry. This study compares the acute inflammatory response to TBI over time, as measured by MPO activity, in the WD and controlled cortical impact (CCI) models. Anesthetized adult Sprague-Dawley rats were traumatized using WD (10-g weight dropped 5 cm) or CCI (4 m/sec, 2.5 mm depth). At 2, 24, 48, or 168 h after trauma, rats (n = 4-5/group at each time) were anesthetized and killed, the brains were removed, and 6-mm coronal slices from traumatized and contralateral hemispheres were assayed for MPO activity. Nontraumatized rats (n = 4) served as controls. Three additional rats underwent a more severe CCI (3 mm depth) with MPO activity assayed at 24 h. A separate group of rats (n = 6) was subjected to WD trauma and killed at 2 weeks after injury for analysis of lesion volume. MPO activity in the traumatized hemisphere was demonstrated at 24 and 48 h in both the WD (0.3152 +/- 0.0472 and 0.3017 +/- 0.0228 U/g, respectively, p < 0.05 vs controls) and CCI (0.1866 +/- 0.0225 and 0.1937 +/- 0.0772 U/g, respectively, p < 0.05 vs controls) models. MPO activity was below the sensitivity of the assay in the control, 2 h, and 168 h groups in both models.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861444 TI - Traumatically induced altered membrane permeability: its relationship to traumatically induced reactive axonal change. AB - Recent studies have suggested that severe forms of traumatic brain injury (TBI) can be associated with direct alterations of the axolemma. The present study evaluated whether injuries of mild to moderate severity are associated with comparable change. To this end, we used extracellular horseradish peroxidase (HRP) to determine if altered axolemmal permeability occurred following the traumatic event. Adult cats received intrathecal infusions of peroxidase and then were prepared for mild to moderate fluid percussion injury. At intervals ranging from 5 min to 3 h, animals were perfused with aldehydes and prepared for the histochemical visualization of the peroxidase, in addition to the immunocytochemical visualization of the neurofilament 68 kD subunit, a long recognized marker of reactive axonal change. The histochemically and immunocytochemically prepared tissue was examined at both the light and electron microscopic level. With mild TBI, the injured animals displayed a repertoire of neurofilament misalignment and axonal swelling consistent with that previously described in our laboratories, yet these changes were not associated with the passage of peroxidase from the extracellular to the intraaxonal compartment. With moderate injury, on the other hand, focal axolemmal permeability change to the extracellularly confined peroxidase was recognized. This peroxidase passage was associated with local mitochondrial abnormalities in addition to an increased packing of the neurofilaments. Over a 3 h course, these neurofilaments began to disassemble, showing a delayed progression of reactive axonal change. Collectively, the results of this investigation suggest that traumatically induced axonal injury involves complex subsets of pathobiology, one evoking rapid primary neurofilamentous change and misalignment, the other eliciting altered membrane permeability concomitant with rapid neurofilament compaction, leading to a delayed progression of reactive axonal change. PMID- 7861445 TI - Endogenous phosphorylation of a 61,000 dalton hippocampal protein increases following traumatic brain injury. AB - Acute biochemical consequences of moderate traumatic brain injury (TBI) include activation of kinases, including protein kinase C (PKC). To determine the possible consequences of PKC activation at the substrate level, we have examined protein phosphorylation patterns 1 h following injury. Although the phosphorylation of most proteins remained unchanged following injury, we observed a significant increase in the phosphorylation of a 61,000 dalton protein (TBI61) in injured rat hippocampus (121% higher than sham control) in vitro. TBI61 phosphorylation could be enhanced by phosphatidyl serine and diacylglycerol or by addition of exogenous PKC. In addition, TBI61 phosphorylation was inhibited by the PKC inhibitor, staurosporine, suggesting further that this protein may be a PKC substrate. These data suggest that TBI increases the phosphorylation of a 61 kD hippocampal protein in vitro. Increases in the protein level and activity of PKC could contribute to this increased phosphorylation. PMID- 7861446 TI - Neurofilament 68 and neurofilament 200 protein levels decrease after traumatic brain injury. AB - We have examined the effect of lateral cortical impact injury on the levels of axonal cytoskeletal proteins in adult rats. Traumatic brain injury (TBI) causes a significant decrease in the protein levels of two prominent neurofilament (NF) proteins, NF68 and NF200. We employed quantitative immunoreactivity measurements on Western blots to examine NF68 and NF200 levels in homogenates of hippocampal and cortical tissue taken at several intervals postinjury. Sham injury had no effect on NF protein levels. However, injury was associated with a significant loss of NF68, restricted to the cortex ipsilateral to the injury site. NF68 loss was detectable as early as 3 h and lasted at least 2 weeks postinjury. Similarly, TBI induced a decrease in NF200 protein, although losses were observed both ipsilateral and contralateral to the injury site. No loss of NF68 or NF200 protein was detected in hippocampal samples obtained from the same injured animals. An increase in the presence of lower molecular weight (MW) NF68 immunopositive bands was associated with the decrease of NF68 in the ipsilateral cortex. This NF68 antigenicity pattern suggests the production of NF68 breakdown products caused by the pathologic activation of neuronal proteases, such as calpain. Putative NF68 breakdown products increase significantly until 1 day postinjury, suggesting that NF degradation may be ongoing until that time and indicating that a potential therapeutic window may exist within the first 24 h postinjury. In summary, these data identify specific biochemical alterations of the neuronal cytoskeleton following TBI and lay a foundation for further investigation of postinjury cytoskeletal changes in neuronal processes. PMID- 7861447 TI - The effects of arterial blood gas values on lesion volumes in a graded rat spinal cord contusion model. AB - The detrimental effects of extreme blood gas values are well documented. However, the range of normal values has not been rigorously defined. There is an ongoing debate concerning the need for ventilation and tight control of blood gas values in spinal cord injury models. Consequently, we performed a retrospective study of 84 rats using a graded rat spinal cord contusion model. Spinal cord ionic lesion volumes were calculated from Na and K shifts at 24 h after injury. Blood gas measurements were obtained 5 min before contusion. For pH values of 7.31-7.46, systemic acidosis was associated with a small but significant decrease in ionic lesion volumes in the 12.5 and 25 g.cm contusion groups (p < 0.05 and p < 0.03, respectively). pH had no effect on ionic lesion volumes in the 50 g.cm contusion group (p > 0.5). PaCO2 values from 23 to 53 mm Hg showed an effect only at 25 g.cm (p < 0.05). PaO2 values of 46-138 mm Hg and calculated HCO3 values of 13-28 mEq/L had no effect on ionic lesion volumes. Two conclusions may be derived from these data. First, mild systemic acidosis is associated with a small reduction in ionic lesion volumes after mild and moderate injury but not after severe injury. This suggests that secondary mechanisms play a greater role in mild injuries. Second, variations in arterial blood gases within clinically normal ranges do not strongly influence 24-h ionic lesion volumes in a graded spinal cord injury model. The effects of blood gas values on ionic lesion volumes are not statistically significant unless the data are adjusted for injury severity. Although blood gas values must be carefully monitored, ventilation may not be needed routinely in rat spinal cord injury models. We recommend maintaining pH values between 7.35 and 7.40, PaCO2 between 35 and 41 mm Hg, and PaO2 greater than 71 mm Hg. PMID- 7861448 TI - Electric field distribution within normal cat spinal cord. AB - Electric currents of small magnitude have been used successfully to induce regrowth of injured spinal cord fibers. The purpose of this study was to determine the potentials and current density distributions on the surface, as well as within the spinal cord, after the application of exogenous electric fields. A 10 microA DC current was applied epidurally to the spinal cord using two different electrode configurations. The two electrode configurations studied were: anode and cathode dorsal (D-D) and anode ventral and cathode dorsal (V-D). Two types of recording electrodes were used to map the potentials on the surface and within the spinal cord. The recording system consisted of glass microelectrodes connected to differential amplifiers. The output was recorded on a polygraph. The current density was more localized on the dorsal surface of the spinal cord for the D-D configuration. In contrast, in the V-D configuration, the current density was greater near the anode on the ventral surface and near the cathode on the dorsal surface of the spinal cord. As a result of the anode being located ventrally, there was a more uniform current density distribution within the spinal cord. PMID- 7861449 TI - Lateral cortical impact injury in rats: cerebrovascular effects of varying depth of cortical deformation and impact velocity. AB - Intracranial pressure (ICP), blood pressure (BP), cerebral perfusion pressure (CPP), and cortical perfusion (LDF) of the contralateral parietal cortex were measured after cortical impact injury in 36 rats. Changes in these physiologic parameters were compared using analysis of variance to a group of 11 rats who received a sham impact. In one series of experiments, the velocity and duration of the impact injury were kept constant, and the severity of the injury was determined by varying the depth of cortical deformation from 2 to 3 mm. The peak pressure inside the skull was directly related to the depth of cortical deformation, and was 93 +/- 16, 182 +/- 18, and 268 +/- 57 mm Hg with the 2, 2.5, and 3 mm deformation, respectively, when the impact velocity was 5 m/sec. With the 2 mm depth injury, there was a transient decrease in BP (p < 0.05) and a 12% decrease in LDF after the impact. With the 2.5 mm depth injury, a small transient increase in ICP and decrease in BP and a 30% decrease in LDF occurred (p < 0.05). ICP then gradually increased throughout the 8 h experiment, becoming significantly greater than the sham-injured animals by 5 h after the impact. LDF gradually returned toward normal throughout the experiment. With the 3 mm depth injury, a marked transient increase in ICP (p < 0.05) and BP (p < 0.05) occurred immediately after the impact. The increase in BP lasted < 5 min, and subsequently the BP decreased to approximately 50 mm Hg for the rest of the experiment. The initial marked increase in ICP lasted 15 min and then remained 5-10 mm Hg higher (p < 0.05) than in the sham-injured animals for the rest of the experiment. LDF decreased by an average of 50% (p < 0.05) immediately after the impact and remained lower than that of the sham-injured animals for the rest of the experiment. In another series of experiments, the depth of cortical deformation was kept constant at 2.5 mm, and the severity of the injury was determined by varying the velocity from 1 to 5 m/sec. The peak ICP was significantly related to the impact velocity, averaging 45 +/- 12, 66 +/- 9, and 182 +/- 18 mm Hg with the 1, 3, and 5 m/sec impact injuries, respectively. The 1 m/sec impact had no effect on ICP and only a transient decrease in BP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7861450 TI - Lateral cortical impact injury in rats: pathologic effects of varying cortical compression and impact velocity. AB - Direct lateral cortical impact through the intact leptomeninges using a pneumatically driven piston produces increasingly severe pathophysiologic derangements with increasing cortical deformation. We studied the histopathologic correlates of cortical impact injury produced by 2 mm, 2.5 mm, and 3 mm deformation in the rat at 5 m/sec. Additionally, the effect of impact velocity at a 2.5 mm deformation was assessed at 1 m/sec, 3 m/sec, and 5 m/sec. The brains were examined 14 days after injury. Cortical contusion maximum cross-sectional area, volume, and the percentage CA1 and CA3 hippocampal neuronal loss correlate with cortical deformation and impactor velocity. Contusion volume increased with increasing cortical deformation. Deformations of 2, 2.5, and 3 mm at 5 m/sec produced contusion volumes of 4.59, 8.9, and 21.68 mm3, respectively. At a fixed cortical deformation of 2.5 mm, contusion volume increased with increasing impact velocity. Impact velocities of 1, 3, and 5 m/sec produced contusion volumes of 5.79, 7.42, and 8.9 mm3, respectively. Hippocampal CA3 neuronal loss increased with increasing cortical deformation. Deformations of 2, 2.5, and 3 mm at 5 m/sec produced neuronal loss of 29%, 48.3%, and 79.5%, respectively. At a fixed cortical deformation of 2.5 mm, hippocampal CA3 neuronal loss increased with increasing impact velocity. Impact velocities of 1, 3, and 5 m/sec produced neuronal loss of 18.25%, 33.75%, and 48.3%, respectively. Hippocampal CA1 neuronal loss was also seen and paralleled cortical deformation and impact velocity. Cortical deformation and impact velocity are critical parameters in producing cortical contusion and must be considered when comparing results using this model. PMID- 7861451 TI - Modification of the cortical impact model to produce axonal injury in the rat cerebral cortex. AB - Diffuse axonal injury (DAI) is a form of brain injury that is characterized by morphologic changes to axons throughout the brain and brainstem. Previous biomechanical studies have shown that primary axonal dysfunction, ranging from minor electrophysiologic disturbances to immediate axotomy, can be related to the rate and level of axonal deformation. Some existing rodent head injury models display varying degrees of axonal injury in the forebrain and brainstem, but the extent of axonal damage in the forebrain has been limited to the contused hemisphere. This study examined whether opening the dura mater over the contralateral hemisphere could direct mechanical deformation across the sagittal midline and produce levels of strain sufficient to cause a more widespread, bilateral forebrain axonal injury following cortical impact. Intracranial deformation patterns produced by this modified cortical impact technique were examined using surrogate skull-brain models. Modeling results revealed that the presence of a contralateral craniotomy significantly reduced surrogate tissue herniation through the foramen magnum, allowed surrogate tissue movement across the sagittal midline, and resulted in an appreciable increase in the shear strain in the contralateral cortex during the impact. To evaluate the injury pattern produced using this novel technique, rat brains were subjected to rigid indentor impact injury of their left somatosensory motor cortex (1.5 mm indentation, 4.5 4.9 m/sec velocity, and 22 msec dwell time) and examined after a 2-7 day survival period. Neurofilament immunohistochemistry revealed numerous axonal retraction balls in the subcortical white matter and overlying deep cortical layers in the right hemisphere beneath the contralateral craniotomy. Retraction balls were not seen at these positions in normals, sham controls, or animals that received cortical impact without contralateral craniotomy and dural opening. The results from these physical modeling and animal experiments indicate that opening of the contralateral dura mater permits translation of sufficient mechanical deformation across the midline to produce a more widespread pattern of axonal injury in the forebrain, a pattern that is distinct from those produced by existing fluid percussion and cortical impact techniques. PMID- 7861452 TI - A modified fluid percussion device. AB - This report examines a modified fluid percussion device with specific improvements made to address deficiencies found in previously reported devices. These improvements include the use of a cylindrical saline reservoir made of stainless steel, placement of the reservoir in a 15-degree head-up position for the easy release of air bubbles, placement of the fluid flushing outlet and the pressure transducer close to the piston on the same plane, with both perpendicular to the direction of the piston, and adjustable reservoir volume to vary the waveform of the pressure pulse, and a metallic central injury screw secured to the animal's skull over the exposed dura. Using this device, midline fluid percussion (MFP) and lateral fluid percussion (LFP) injuries were performed in 70 rats. Histopathologic findings included diffuse axonal injury in the MFP model and cortical contusion in the LFP model. Survival rate was 41.4% in MFP animals and 100% in LFM animals when the device settings were 178 mm3 of the cylindrical reservoir and 50 degrees-60 degrees in height of the pendulum. Our results suggest that this modified fluid percussion device may offer significant improvements over previously reported fluid percussion models for use in experimental head injury. PMID- 7861453 TI - Rapid infusion system for neurosurgical treatment of massive intraoperative hemorrhage. AB - Using an illustrative case of severe closed head injury that resulted in a posterior fossa epidural hematoma (EDH) and supratentorial epidural/subdural hematomas (SDH), the massive blood losses associated with operative repair of the torn sigmoid sinus and the significant fluid losses associated with refractory diabetes insipidus were treated by the intraoperative use of the Rapid Infusion System (RIS, Haemonetics). The RIS can rapidly infuse warm blood, crystalloid, or colloid at rates up to 1.5 L/min, thereby limiting the commonly associated hypotension, hypothermia, and coagulopathies. During the suboccipital craniectomy for evacuation of the EDH and repair of the sigmoid sinus, the patient required 18 units of blood replacement secondary to a large tear in the sigmoid sinus. During a separate craniotomy for evacuation of the SDH, the patient also developed diabetes insipidus, which increased the operative fluid replacement to 39 L. Despite these massive blood and fluid losses, the RIS limited the hypotension to less than 2 min and prevented hypothermia and the frequently associated coagulopathies. When used in a neurosurgical setting associated with massive blood and/or fluid losses, the RIS accomplishes three important objectives: (1) rapid infusion of intravenous fluids for maintaining perfusion pressure, (2) rapid warming of fluids despite high intravenous infusion rates of cold crystalloids, thereby preventing intraoperative hypothermia, and (3) continuous monitoring of infusion rates and totals. PMID- 7861454 TI - Evaluation of direct medical costs related to cancer. PMID- 7861455 TI - Serologic detection of human papillomavirus-related anogenital disease: new opportunities and challenges. PMID- 7861456 TI - Discovery may improve transplant success. PMID- 7861457 TI - Gene therapy depends on finding the right vector. PMID- 7861458 TI - Libraries face challenge of providing computer access. PMID- 7861459 TI - BRCA1 patent dispute resolved; NIEHS included. PMID- 7861460 TI - Canadian mammography study to be reviewed by outside team. PMID- 7861461 TI - Stage, age, comorbidity, and direct costs of colon, prostate, and breast cancer care. AB - PURPOSE: This study was conducted to evaluate the effect of stage at diagnosis, age, and level of comorbidity (presence of other illness) on the costs of treating three types of cancer among members of a health maintenance organization. METHODS: Among 388,000 members enrolled anytime during 1990 and 1991 in Group Health Cooperative (GHC) of Puget Sound (Washington State), we estimated the total and net direct costs of medical care for colon, prostate, and breast cancers, including both incident (290, 554, and 645 patients, respectively) and prevalent (1046, 1295, and 2299 patients, respectively) cases. We summarized costs for initial, continuing, and terminal phases of care. Net costs were the difference between the costs of the care of each case subject and the average costs of the care for all enrollees without the cancer of interest who were of the same sex and in the same 5-year age group. Differences in estimated total and net costs by stage at diagnosis, age, and comorbidity were separately evaluated using multivariate regression modeling. All P values were two-sided. Comorbidity was based on a score calculated from 1988 pharmacy data. RESULTS: Total costs of initial care increased with stage at diagnosis for colon (P = .0013) and breast (P < .0001) cancer cases, but not for prostate cancer cases. Total initial costs decreased with age for prostate (P = .0225) and breast (P = .0002) cancers but did not change with degree of comorbidity for any of the three cancers. Total continuing medical care costs increased with stage at diagnosis for colon (P < .0001) and breast (P < .0001) cancer cases but not for prostate cancer cases. Total terminal care costs were similar by stage for all three cancers. Net initial costs differed with stage for all three cancers (P < .05). Net continuing care costs increased with stage (P < .0001) and decreased with age (P < .001) for colon and breast cancers but not for prostate cancer. Net continuing care costs decreased with comorbidity for all three cancers (P = .004, P = .011, and P < .0001 for colon, prostate, and breast cancers, respectively). Among regional stage cancers, continuing care costs decreased with age for colon (P < .0017) and breast (P = .033) cancers but not for prostate cancers. CONCLUSIONS: The results show that total costs vary by stage at diagnosis and age, but the patterns of variation differ for each cancer. Costs of cancer are not simply additive to costs of other conditions. IMPLICATIONS: More needs to be done to explore the reasons and implications of age-related cost differences. Cost-effectiveness analyses of cancer control interventions that shift cancer stage distributions may need to consider both the age and comorbidity of the target populations. PMID- 7861462 TI - Comparison of human leukocyte antigen DR-DQ disease associations found with cervical dysplasia and invasive cervical carcinoma. AB - BACKGROUND: Human leukocyte antigen (HLA) molecules, whose biological role is in the regulation of immune responses to foreign antigens and in discrimination of self from non-self antigens, are encoded by a series of closely linked genetic loci found on chromosome 6. Although the evidence for a link between HLA and cervical cancer has been controversial, it has been recently reported that certain HLA class II haplotypes (linked class II alleles) are positively associated with invasive cervical cancer, while other class II haplotypes are negatively associated or protective. Since HLA associations between human papillomavirus type 16 (HPV16)-mediated cancer cases and non-HPV16-mediated cancer cases have been found to be different, this suggests that specific HLA class II haplotypes may influence the immune response to HPV infection and may affect the risk of acquiring invasive cervical carcinoma. PURPOSE: This study was conducted to determine if the same HLA class II haplotypes that are associated with invasive cervical carcinoma are also associated with cervical dysplasia (presumed precursors of invasive cervical cancer). METHODS: We have examined HLA DR-DQ haplotypes among 128 Hispanic women from New Mexico with biopsy-confirmed cervical dysplasia in a case-control study using sensitive DNA-based polymerase chain reaction amplification and sequence-specific oligonucleotide probe hybridization methods to detect the presence and type of HPV and to detect allelic polymorphism in the HLA DRB1 and DQB1 loci. RESULTS: Dysplasia cases were divided into two groups for comparison to controls: severe dysplasia/carcinoma in situ (CIS), and slight/moderate dysplasia. The frequency distribution of HLA class II haplotypes among the HPV16-positive severe dysplasia/CIS cases had a statistically significant (two-tailed P < .005) difference compared with controls, whereas haplotypes among the severe dysplasia/CIS cases containing HPV types other than HPV16 did not show statistically significant frequency differences. DR-DQ haplotypes previously found to be associated with HPV16 invasive cervical carcinomas were also associated with HPV16-positive severe dysplasia/CIS. However, no statistically significant haplotype frequency difference was observed between slight/moderate dysplasia cases and controls. In addition, we noted a DQA1-DQB1 haplotype negatively associated with severe dysplasia/CIS but not with invasive cervical cancers. CONCLUSIONS: Our results strongly suggest that certain HLA haplotypes confer an increased risk for severe cervical dysplasia and invasive cervical carcinoma following HPV16 infection. IMPLICATIONS: Further molecular studies are needed to identify HLA alleles or haplotypes that may provide increased susceptibility to HPV-associated cervical disease. PMID- 7861463 TI - Estrogen receptor gene analysis in estrogen receptor-positive and receptor negative primary breast cancer. AB - BACKGROUND: In breast cancer patients, about two thirds of the tumors are estrogen receptor (ER)-positive and one third are ER-negative. The molecular mechanisms leading to the ER-negative phenotype are poorly understood. Nearly all ER-negative and about 40% of ER-positive cancers are resistant to endocrine therapy. PURPOSE: In this study, we examined the entire coding region of the ER gene in ER-positive and ER-negative primary breast tumors to determine whether deletions/insertions or point mutations might account for the ER-negative phenotype. METHODS: We amplified exons 1 through 8 of the ER gene in 118 ER positive and 70 ER-negative primary breast tumors and searched for mutations by single-strand conformation polymorphism analysis, denaturing gradient gel electrophoresis, and DNA sequencing. RESULTS: Both ER-negative and ER-positive tumors contained neutral polymorphisms in codons 10 [TCT-->TCC (Ser)], 87 [GCG- >GCC (Ala)], 243 [CGC-->CGT (Arg)], 325 [CCC-->CCG (Pro)], and 594 [ACA-->ACG (Thr)]. There was no correlation of any of the polymorphic alleles with the ER phenotype or other clinicopathologic parameters including tumor type, size, grade, or stage. However, the polymorphism in codon 325 showed a strong association with a family history of breast cancer (P = .0005). This association was observed both in premenopausal and postmenopausal patients. Despite extensive searching in exons 1 through 8, we found no deletions/insertions and only two missense mutations in codons 69 [AAC (Asn)-->AAG (Lys)] and 396 [ATG (Met)-->GTG (Val)] of the same ER-negative tumor. Thus, only 1% of the primary breast cancers had point mutations in the ER gene. CONCLUSIONS: In the majority of primary breast cancers, the ER-negative phenotype is not the result of mutations in the coding region of the ER gene, but is due to deficient ER expression at the transcriptional or post-transcriptional level. IMPLICATIONS: The correlation reported previously, as well as our current findings, suggest that further investigations are warranted to understand the possible linkage of the ER gene locus to hereditary breast cancer. PMID- 7861464 TI - Inhibition of mammary carcinogenesis by treadmill exercise. PMID- 7861465 TI - Re: Mutagen sensitivity as a risk factor for second malignant tumors following malignancies of the upper aerodigestive tract. PMID- 7861466 TI - Re-dedicating ourselves to community activism, support, teaching,and active service. The Lawrence Winfield Long, Sr, MD, Memorial Lecture. PMID- 7861467 TI - For African Americans: real health-care reform or business as usual? PMID- 7861468 TI - Economically disadvantaged females' perceptions of breast cancer and breast cancer screening. AB - This study examined 500 economically disadvantaged females' perceptions and screening practices regarding breast cancer. The vast majority of respondents did not identify themselves, or economically disadvantaged women in general, as more susceptible to breast cancer. Those who were the most knowledgeable about breast cancer were significantly more likely than the least knowledgeable to perceive themselves as more susceptible to breast cancer, to perceive breast cancer as less severe, to perceive fewer barriers, and to perceive more benefits to screening for breast cancer. Fifty-four percent of the women claimed they had previously had a mammogram. A series of t-tests were conducted to see if breast cancer knowledge or health beliefs would discriminate between those who had and those who had not had a mammogram. The only difference between the two groups was that those who had a mammogram were more likely to perceive greater benefits of mammography screening. The results of this survey indicate that there is considerable room for improvement in knowledge, perceptions, and practices of economically disadvantaged women regarding breast cancer. PMID- 7861469 TI - Colorectal cancer and cardiac risk reduction using computer-assisted dietary counseling in a low-income minority population. AB - Three nurses offered computer-assisted 24-hour dietary analysis to patients waiting to see their physicians in a general medicine clinic in a public hospital. The nurses showed the participants their results, recommended food substitutions, and suggested reevaluation of the patients' diets at their next scheduled clinic visit. Follow-up data showed a decrease in fat, dietary cholesterol, kilocalories, and weight, and an increase in dietary fiber. This article discusses the use of this and other interventions to assist low-income minority patients in understanding and complying with dietary recommendations that promote cardiovascular health and decrease the risk of developing colorectal cancer. PMID- 7861470 TI - The role of the family in psychosocial adaptation to physical disabilities for African Americans. AB - The psychosocial adjustment of patients who are experiencing physical disabilities is examined within the context of a family ecological approach. Historical and sociocultural characteristics of African-American families are delineated and explored in terms of their potentially positive impact on the adjustment process. Four family strengths are delineated: strong kinship bonds, strong religious orientation, family role flexibility, and strong education/work ethic. The authors demonstrate how these various assets interact reciprocally in the family lives of those individuals who are disabled. Contrary to the predominant deficit theories, a fresh asset-oriented approach is provided. A model of the family adjustment process of African-American clients with disabilities is presented, and some of the important strengths of the African American family system are examined. Finally, a family strengths model is applied to the therapeutic process. PMID- 7861471 TI - Evaluation of massive volume replacement in the penetrating trauma patient. AB - The records of 163 penetrating trauma patients who required surgery in a 36-month period between 1988 and 1990 were reviewed. Those patients with head trauma were excluded. Thirty patients were identified as having: similar Injury Severity Scores (ISS), received at least 8 L of crystalloid, and received at least 4 units of packed red blood cells during the first 24 hours after admission. There were 22 (73%) survivors and 8 (27%) nonsurvivors. Charts were reviewed for a variety of variables to determine which characteristics distinguished nonsurvivors from survivors. The mean ISS was 30.5 +/- 5.5. As a group, nonsurvivors received more blood transfusions (14.9 +/- 4.9 versus 5.0 +/- 1.14), had longer durations of shock (55.6 +/- 18 minutes versus 19.3 +/- 11.7 minutes), and had lower core body temperatures (92.6 degrees F +/- 2.2 versus 95.1 degrees F +/- 2.4) than survivors. Nonsurvivors also had lower hemoglobin levels (7.84 +/- 1 versus 9.1 +/- 2.3) and platelet counts (134.2 +/- 14.1 versus 188.6 +/- 6.3) than survivors. In addition, nonsurvivors demonstrated greater incidence of three major risk factors than did the survivors: hypothermia (75% versus 41%), acidosis (100% versus 27%), and coagulopathy (62% versus 4.5%). Therapeutic measures to limit these risk factors for increased mortality may maximize the chance of survival in these patients. PMID- 7861472 TI - Characteristics of African-American college students with HIV/AIDS. AB - This article examines the risky sexual behaviors, condom and drug usage, sexually transmitted diseases (STDs), and attitudes of African-American college students with the human immunodeficiency virus (HIV), which is the precursor of the acquired immunodeficiency syndrome (AIDS). A total of 408 (199 males, 209 females) African-American college students, representing 75% of the students enrolled in a southern university, were surveyed. The results revealed that 3.18% of the students reported having HIV/AIDS. The students with HIV/AIDS exhibited significant deficits in AIDS knowledge, particularly information concerning the transmission of HIV/AIDS. While subjects with HIV/AIDS did not differ from subjects without HIV/AIDS with regard to their perceived risk of being exposed to AIDS or their attitudes about using condoms, a significantly larger percentage of subjects with HIV/AIDS reported that they "always" used condoms with their partner. Nevertheless, subjects with HIV/AIDS were more likely to engage in anal intercourse, experience sex with prostitutes, and use drugs. Sexually transmitted diseases were more prevalent among subjects with HIV/AIDS, and syphilis was found to be the best predictor of HIV/AIDS. PMID- 7861473 TI - Bilateral ethmoid sinusitis with unilateral proptosis as an initial manifestation of metastatic prostate carcinoma. AB - This article presents a case of bilateral ethmoid sinusitis with unilateral proptosis as a presenting sign of an unsuspected prostate carcinoma. A 59-year old Hispanic male presented to his primary care physician with nasal congestion and rhinitis. He was treated with antibiotics and antihistamine decongestants for 3 weeks without improvement. A trial of steroids resulted in brief improvement followed by a rapid onset of nasal obstruction with proptosis. A computed tomography scan revealed opacification of the ethmoid sinus with right proptosis. The presumptive diagnosis was orbital cellulitis secondary to chronic ethmoid sinusitis. Endoscopic sinusotomy and bilateral ethmoidectomies were performed. Biopsy results returned as metastatic adenocarcinoma, probably of prostate origin. Urological work-up and evaluation with biopsy confirmed the diagnosis of prostatic carcinoma. The patient was treated with chemotherapy and radiation therapy. He died 7 months later with disseminated disease. PMID- 7861474 TI - The cofactor effect of genital ulcers on the per-exposure risk of HIV transmission in sub-Saharan Africa. AB - The goal was to estimate the cofactor effect of genital ulcer disease (GUD) on the risk of HIV transmission during a single heterosexual exposure. The relation between the risk ratio observed in an epidemiological study and the per-exposure cofactor effect was investigated. Given simple assumptions, we show that observed risk ratios are expected to be very much smaller than per-exposure cofactor effects and to decrease as the observation period increases. Data from longitudinal studies of female commercial sex workers and men in Nairobi were reanalysed. The data are consistent with GUD cofactor effects per sexual exposure of 10-50 for male to female transmission, and of 50-300 for female to male transmission. Although subject to wide margins of error, these estimates indicate that GUD may be responsible for a high proportion of heterosexually acquired HIV infections in sub-Saharan Africa, supporting the potential role of STD control as an effective intervention strategy against HIV. PMID- 7861475 TI - Gastric emptying in acute uncomplicated falciparum malaria. AB - Gastric emptying by paracetamol absorption test was performed in 22 patients with uncomplicated falciparum malaria. There was no significant difference in the time to reach the maximum plasma paracetamol concentration (Tmax) and the maximum plasma paracetamol concentration (Cmax) of the patients during acute illness and convalescence. We concluded that gastric emptying was not altered in acute uncomplicated falciparum malaria. PMID- 7861476 TI - Antibiotic availability and multiresistant coliforms in a rural Ugandan hospital. AB - Twenty-seven strains of coliforms (Enterobacteriaceae) isolated at Kisiizi Hospital, Uganda, were tested for their sensitivity to antibiotics. Sixteen of the 18 patient strains were identified as Escherichia coli, but biochemical analysis, serotyping, plasmid profile and antibiogram showed them to be heterogeneous. Resistance was very common to the antibiotics available in the community (ampicillin, chloramphenicol, tetracycline and trimethoprim), but was much less frequent for the agents used only in the hospital (gentamicin, ciprofloxacin and nitrofurantoin). A correlation was noted between the presence of large plasmids (150 kb or larger) and resistance to amoxicillin in patient strains of E. coli. The nine strains of coliform from the water supply were more heterogeneous and less resistant. The availability of antibiotics in the community seems linked to the development of multiresistant coliforms, which in a Ugandan context are very difficult to treat, and even more difficult to prevent. PMID- 7861477 TI - Treatment of malaria outside the formal health services. AB - Self-medication for malaria is widely practised around the world, and although many home treatment episodes are successful, the risk of under or over-dosing is always present. Reasons for the widespread use of self-medication range from the distance and cost of seeking care from the formal health services to cultural beliefs which suggest that traditional care is more appropriate, and even that modern care may be fatal. But self-medication constitutes an important resource for malaria treatment, and much could be done to improve the self-medication practices of the population. Measures to be taken include dissemination of clear messages about malaria as a part of health education, formulation of realistic treatment policies which take account of resource constraints, lowering or removal of economic barriers, especially user charges, and further research into cultural beliefs about malaria and ways to promote compatibility of beliefs with appropriate treatment. If these suggestions could be taken into account in developing malaria treatment strategies, the chances of success would be greatly enhanced. PMID- 7861478 TI - Use of fractionated urinary filarial antigen in the diagnosis of human filariasis. AB - Fractionated urinary filarial antigen UFA C2 has shown high antigenic activity after absorption of urinary albumin present in the fraction. As little as 500 ag (10(-18) g) of albumin absorbed UFA C2, labelled as UFA C2-A, was found to be sufficient to detect filarial antibody. Stick enzyme immunoassay to assess the immunodiagnostic potential of UFA C2-A indicated filarial IgG antibody in 89% of microfilaraemic (mf) cases, 84% of clinical filariasis and 7% of endemic normals. UFA C2-A was found to be present in circulation in active as well as clinical infections as observed by inhibition assay using UFA C2-A penicillinase conjugate. Eighty-six per cent of mf, 50% of clinical cases and 6% of endemic normal subjects revealed parasite antigen to UFA C2-A on further serological analysis. None of the non-endemic normal sera showed the presence of filarial antibody/antigen to UFA C2-A. Furthermore, the test to determine phosphorylcholine (PC) bearing epitopes in UFA C2-A indicated no immunological reaction with anti-PC monoclonal antibody by avidin-biotin enzyme linked immunosorbent assay (ELISA). The highly sensitive and more easily obtainable non PC urinary filarial antigen, UFA C2-A, is of great immunodiagnostic interest for lymphatic filariasis. PMID- 7861479 TI - An environmental classification of housing-related diseases in developing countries. AB - A preliminary environmental classification of housing-related diseases in developing countries is presented. This groups these diseases into six categories: those related to defects in (1) buildings and the peridomestic environment, (2) water supply, (3) sanitation, (4) refuse storage and collection and (5) food storage and preparation; and (6) industry-related diseases resulting from housing location (close to polluting industries or on contaminated land) and from the use of the home as a workplace. Each category has three subcategories: communicable diseases (including zoonoses), non-communicable diseases, and mental illnesses and psychosocial disorders. PMID- 7861480 TI - Immunomonitoring of filarial patients during DEC therapy in an endemic area: a seven-year follow-up. AB - A group of 27 Wuchereria bancrofti infected persons from an endemic area, who had undergone treatment with diethylcarbamazine (DEC), were followed for 7 years to understand its effect on microfilaraemia, immune status and on the recurrence of infection. Treatment with DEC was for 14 days (day 1, 1 mg kg-1 body weight, day 2, 2 mg kg-1 body weight and from day 3 onwards 6 mg kg-1 body weight) followed by one dose (6 mg kg-1 body weight) on days 360, 540 and at the end of years 2, 3, 4, 6 and 7. After a 2-year follow-up the patients were divided into two groups. Group A consisted of cases that showed no reappearance of microfilariae (mf) and Group B of those cases that showed reappearance of mf. Further follow-up in the next 5 years showed that none of the cases in Group A were positive for mf at any time. In contrast, mf were detected in Group B in 14, 15, 27 and 33% of the cases followed at the end of years 3, 4, 6 and 7 respectively. Both groups showed a decrease in filarial IgG antibody and mf excretory-secretory antigen levels in the initial 4 years followed by increased levels at the end of years 6 and 7. The reappearance of filarial antibody and antigen in 50-70% of Group A and 68-100% of Group B at the end of year 7 suggests the existence of active infection in these cases. No cases followed in this study developed clinical symptoms. This study shows that long-term DEC therapy and immunomonitoring of mf patients is essential in an endemic area for arresting transmission and prevention of pathology associated with clinical manifestations. PMID- 7861481 TI - Epidemiological studies on Schistosoma mansoni infection in the western region of Saudi Arabia using the potassium hydroxide stool digestion technique. AB - The potassium hydroxide stool digestion technique was used in 30 sites in the Western Region of Saudi Arabia (Hijaz highlands and Tihamah lowlands) for epidemiological studies of S. mansoni. The mean prevalence rate in 2792 individuals (1490 males and 1302 females) in Hijaz highlands (20 sites) was 6.09 (0.5-20.1%) and the geometric mean egg count of stool was 110.8 (63-285). The prevalence rate was greater in males (8.06%) than in females (3.79%). The peak prevalence in males was in the age group 11-15 years, and 31-50 years in females. In 10 sites in the Tihamah lowlands a total of 1771 persons were examined for schistosomiasis. Only one site was recorded with S. mansoni, at a prevalence rate of 0.05%; S. haematobium was recorded in two sites at prevalence rates of 0.55 and 1.13%. Praziquantel therapy (40 mg kg-1) of 170 S. mansoni cases showed a cure of 85-98% at 1-6 months after treatment and a considerable reduction in stool arithmetic mean egg count. Schistosoma haematobium was not recorded in the Hijaz highlands. PMID- 7861482 TI - Primary hepatocellular carcinoma and viral hepatitis B and C infection in Bangladeshi subjects. AB - Potential risk factors for the development of primary hepatocellular carcinoma and the prevalence and role of infection with viral hepatitis B and hepatitis C were investigated in 54 adult patients of Bangladeshi origin (45 male, age range 20-75 years), comprising 46 patients resident in Bangladesh (Group 1) and 8 patients who had emigrated to the UK 10-20 years previously (Group 2). Of the 46 patients in Group 1 (37 male), 16 had hepatocellular carcinoma, 10 had uncomplicated cirrhosis, and 20 had a clinical history of chronic viral hepatitis of more than 6 months' duration. Total hepatitis B virus marker positivity was 82.6%, significantly higher than in Group 2 patients (P < 0.001). Thirty-six per cent were hepatitis B surface antigen positive, 66% were hepatitis Be antigen positive and 45.3% were positive for hepatitis C virus antibody. Taking only the 16 patients with hepatocellular carcinoma, hepatitis B surface antigen positivity was 38%, hepatitis Be antigen 66% and positivity to hepatitis C virus antibody was 56%. The 8 patients with hepatocellular carcinoma in Group 2 were all male and aged between 45 and 56 years. Of these, 3 (38%) cases were positive for hepatitis B surface antibody and none was positive for hepatitis B surface antigen or antibody to hepatitis C virus (3 cases tested). Presenting features of HCC in the two groups differed with a short clinical history of tender abdominal mass in Group 1 and a gradual onset of jaundice in Group 2 UK-resident Bangladeshi subjects. PMID- 7861483 TI - Diarrhoea in piglets and monkeys experimentally infected with Balantidium coli isolated from human faeces. AB - Ten piglets and four monkeys free from Balantidium were dosed with human faecal homogenate which contained 1.2 x 10(4)-4.8 x 10(4) B. coli cysts. The infection resulted in severe diarrhoea in piglets 1-6 and hydrocortisone-treated monkeys 1 2, moderate diarrhoea in piglets 7-10 and a subclinical infection in monkeys 3-4. In piglets 1-3 and monkeys 1-2, heavy infection of the intestinal mucosa extended from the terminal ileum to the rectum and the mucosa was severely damaged. In piglets 4-10, infection was heavy in the large intestine with moderate mucosal damage. PMID- 7861484 TI - The impact of human immunodeficiency virus on response to treatment and recurrence rate in patients treated for tuberculosis: two-year follow-up of a cohort in Lusaka, Zambia. AB - To examine the effect of HIV on response to treatment and recurrence rate in patients with tuberculosis (TB), we have followed 239 previously untreated, adult, TB patients in a prospective cohort study in Lusaka, Zambia. One hundred and seventy-four (73%) were HIV-1 antibody positive. Patients with sputum smear positive, miliary, or meningeal TB were prescribed 2 months daily streptomycin, thiacetazone, isoniazid, rifampicin, pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. Thirty-five per cent of HIV-positive (HIV+ve) and 9% of HIV-negative (HIV-ve) patients were known to have died before the scheduled end of treatment. Surviving HIV+ve patients showed weight gain and improvement in symptoms and laboratory and radiological findings similar to HIV-ve patients. The risk of cutaneous drug reaction was 17% (95% CI: 12-25%) in HIV+ve, and 4% (1-13%) in HIV-ve patients. Severe rashes were attributed to thiacetazone. Recurrence of active TB was examined among 64 HIV+ve and 37 HIV-ve patients who successfully completed treatment, with mean follow-up after the end of treatment of 13.5 and 16.8 months, respectively. The rate of recurrence was 22/100 person years (pyr) for HIV+ve patients and 6/100 pyr for HIV-ve patients, giving a recurrence rate ratio of 4.0 (95% CI 1.2-13.8, P = 0.03). PMID- 7861485 TI - Carcinoma in situ of the bladder. PMID- 7861486 TI - Epidermal growth factor precursor is present in a variety of human renal cyst fluids. AB - Progressive human renal cystic diseases are characterized by proliferation of the epithelial cells lining the cyst. The kidney synthesizes epidermal growth factor and its presence in renal cyst fluid might contribute to renal epithelial cell proliferation. We screened autosomal dominant polycystic kidney disease, acquired renal cystic disease, the von Hippel-Lindau syndrome, multilocular cystic nephroma, multicystic dysplastic kidney disease and simple cyst fluids for the presence of epidermal growth factor by radioreceptor assay, specific radioimmunoassay, immunoprecipitation and immunoblotting. Multiple epidermal growth factor immunoreactive species of approximately 180 kD. and lower molecular weights were present in almost all cyst fluids examined, suggesting endogenous synthesis and limited proteolysis of epidermal growth factor precursor protein in cyst fluid. Tamm-Horsfall protein was detected by enzyme-linked immunosorbent assay in most cysts (for example 55 of 59 autosomal dominant polycystic kidney disease samples). The majority of simple and autosomal dominant polycystic kidney disease renal cysts contained high sodium ion concentration, epidermal growth factor precursor protein and Tamm-Horsfall protein, characteristic of the early thick ascending limb. Rather than the mere presence of epidermal growth factor in renal cyst fluids, increased sensitivity to epidermal growth factor or other mitogens present in renal cyst fluid may be pathogenic in progressive renal cystic disease. PMID- 7861487 TI - Long-term incidence and risk factors for recurrent stones following percutaneous nephrostolithotomy or percutaneous nephrostolithotomy/extracorporeal shock wave lithotripsy for infection related calculi. AB - A study was done to determine the long-term incidence and cause of recurrent stones following percutaneous nephrostolithotomy alone (13 patients) or combined with extracorporeal shock wave lithotripsy (31) for management of documented infection related struvite renal calculi. The patients were followed for 12 to 111 months (mean 41.7) to censorship or time of new stone formation. Of these patients 12 (27%) had recurrent stones at 12 to 61 months (mean 32.3) after treatment. As determined by a Kaplan-Meier estimate, the risk of new stone formation 5 years after treatment was 36.8%. Potential risk factors for recurrence, including history of stones, associated anatomical abnormalities, procedure used, radiographic status at completion of treatment and recurrent infection during followup, were analyzed with Cox's proportional hazards model. Of these potential risk factors, only an associated anatomical abnormality was found to influence significantly the rate of recurrent stone formation (p = 0.005). We conclude that continued surveillance for recurrent stones is mandatory even for patients initially rendered stone-free and those who maintain sterile urine. In addition, because the presence of a significant anatomical or functional urinary tract abnormality places a patient at much higher risk for recurrence, we suggest that subsequent studies be stratified as to the presence or absence of these abnormalities. PMID- 7861488 TI - Comparison of first generation (Dornier HM3) and second generation (Medstone STS) lithotriptors: treatment results with 13,864 renal and ureteral calculi. AB - Some reports have shown a decreased effectiveness of extracorporeal shock wave lithotripsy (ESWL*) with newer lithotriptors. We used a first generation unmodified Dornier HM3 lithotriptor to treat 5,698 patients with renal and ureteral calculi and a second generation Medstone STS device to treat 8,166 patients with renal and ureteral calculi. The treatment results were compared using the chi-square test to determine statistical significance. The stone-free rate, retreatment rate and post-ESWL secondary procedure rate were 69.5%, 4.4% and 3.1%, respectively, with the Dornier HM3 device and 72.1%, 4.9% and 2.3%, respectively, with the Medstone lithotriptor for single renal stones, and 81.5%, 5.2% and 5.5%, respectively, with the Dornier HM3 and 83.2%, 5.2% and 5.0%, respectively, with the Medstone device for single ureteral stones. There were no statistically significant different results between a second generation tubless Medstone STS lithotriptor and the gold standard unmodified Dornier HM3 instrument. PMID- 7861489 TI - Ungated Medstone outpatient lithotripsy. AB - Ungated lithotripsy has raised the specter of possible cardiac arrhythmias. We reviewed ungated outpatient lithotripsy performed on 82 patients to evaluate the incidence of arrhythmias encountered and time saved. All patients were chosen in a random nonselected, prospective fashion. All treatments were performed on a mobile Medstone 1050 STS lithotriptor. The incidence of arrhythmias was 21%. All but 2 arryhthmias were benign and all reversed with gating. No arrhythmias occurred during treatment of right ureteral stones. In the left ureter only 1 patient had benign premature ventricular contractions during treatment. Arrhythmias occurred at 20 to 24 kv. in 20% of patients with right renal stones and 31% with left renal stones. All arrhythmias resolved with gating. No arrhythmias were encountered at an energy level of less than 20 kv. There was no evidence of electrocardiographic changes up to 1 hour after treatment. Pharmacological manipulation to maintain a heart rate of 100 may allow a treatment time of approximately 24 minutes. With ungating the rate may reach 120, allowing for a treatment time of approximately 20 minutes. In this series average ungated lithotripsy time was 36 minutes. In comparison, the average treatment time in 20 patients undergoing gated lithotripsy was 38.7 minutes. It is not clear from this study whether persistent ungated lithotripsy would have precipitated any life threatening arrhythmias since our practice has been to terminate the procedure and re-gate the shocks at the first sign of any persistent change in cardiac rhythm. Our data indicate that ungated lithotripsy with the Medstone device is safe when simple monitoring rules are followed. PMID- 7861490 TI - Protective effects of nifedipine and allopurinol on high energy shock wave induced acute changes of renal function. AB - In a prospective randomized study, the effects of a calcium antagonist (nifedipine) and a xanthine oxidase inhibitor (allopurinal) on high energy shock wave induced impairment of renal function were examined. A total of 40 patients with renal pelvis or caliceal stones undergoing anesthesia-free extracorporeal shock wave lithotripsy (ESWL) without auxiliary measures was randomly assigned to 4 groups. Group 1 received no medication and the others received nifedipine (group 2), allopurinol (group 3) or nifedipine plus allopurinol (group 4), respectively. Nifedipine (20 mg. each) or allopurinol (0.2 gm. each) was given orally 3 times a day for a total of 4 days beginning the night before ESWL. To assess renal function the urinary excretions of beta 2-microglobulin, albumin and Tamm-Horsfall protein were determined by radioimmunoassay. After ESWL there was a significant increase in urinary beta 2-microglobulin and albumin (p < 0.001), and the urinary Tamm-Horsfall protein decreased significantly (p < 0.01) compared with before ESWL in group 1. In groups 2 and 4, however, all of the parameters after ESWL were not significantly different compared with the values before ESWL. Although the levels of urinary beta 2-microglobulin and albumin after ESWL were significantly higher (p < 0.05) than the pre-ESWL levels in group 3, the changes in urinary albumin and Tamm-Horsfall protein were milder in group 3 than in group 1. In addition, the urinary albumin level in group 2 and the urinary beta 2 microglobulin or albumin level in group 4 were less significantly different (p < 0.05) than the levels in group 1. All parameters before ESWL were not significantly different among the groups. Our results indicated that nifedipine and/or allopurinol exhibits a protective effect on high energy shock wave induced renal damage. PMID- 7861491 TI - Extracorporeal shock wave lithotripsy for renal stones with renal cysts present. AB - While reports differ on the effect of extracorporeal shock wave lithotripsy (ESWL*) on renal cysts, little has been written on the stone-free status following ESWL for renal calculi with renal cysts present. We studied 13 patients with renal stones plus renal cysts, and only 6 (46%) were stone-free at 3 months after ESWL. While the number of cases is small, it is believed that renal cysts may interfere with the passage of stone fragments due to the impediment of drainage, and urinary stasis from the stretching and distortion of the caliceal system by the renal cysts. PMID- 7861492 TI - Shock wave lithotripsy: what progress have we made? Are refinements needed? PMID- 7861493 TI - Management of hemorrhage after percutaneous renal surgery. AB - Renal hemorrhage is the most worrisome complication of percutaneous renal surgery. Between August 1983 and August 1992 we performed 2,200 percutaneous renal operations, with 17 patients (0.8%) requiring angiography and embolization for significant bleeding uncontrolled by the usual measures. The angiographic diagnoses were arteriovenous fistula in 7 patients, pseudoaneurysm in 4, fistula and pseudoaneurysm in 2, and lacerated renal vessels in 2. A total of 15 patients required no further treatment after embolization, while 2 underwent either partial nephrectomy or open exploration. No risk factors for hemorrhage could be identified. We recommend angiography and embolization under 3 conditions; 1) in the immediate postoperative period when clamping of the nephrostomy tube and a tamponade balloon catheter fail to control hemorrhage (24% of our series), 2) in the early postoperative period (2 to 7 days) when the patient requires 3 or 4 units of blood after replacement of the initial blood loss (41% of our series) and 3) for sudden hemorrhage more than 7 days postoperatively (35% of our series). PMID- 7861495 TI - Caliceal fistula formation following renal transplantation: management with partial nephrectomy and ureteral replacement. AB - Six patients in this series of 543 renal transplants (1.10%) suffered a post transplant renal segmental infarct of the donor kidney because of occlusion of an accessory renal artery. Five grafted kidneys had multiple renal arteries. Patients presented with symptoms of a caliceal fistula and were treated by partial (25 to 40%) transplant nephrectomy, followed by closure and tissue coverage with either parietal peritoneum (4 patients) or lyophilized human dura mater sealed with fibrin (2). In 2 cases the renal ischemia and necrosis involved the ureter, and a pyelo-pyelostomy was performed. One patient died of cardiorespiratory complications immediately postoperatively. Five years postoperatively all kidneys functioned well without recurrence of fistula and 5 patients returned to a normal life-style. The combination of radical excision and tissue closure, plus ureteral substitution when needed was an effective treatment that prevented loss of the graft. PMID- 7861494 TI - Nephrectomy for traumatic renal injuries. AB - During a 16-year period 2,521 patients presented to our institution with renal trauma. Renal exploration was performed in 195 patients (202 renal units), with 31 units requiring exploration alone, 145 repair and 26 nephrectomy, yielding an overall nephrectomy rate of 13%. A detailed review of these 26 patients identified them as a unique population: all had major renal injuries, and as a group they demonstrated significantly higher rates of shock, injury severity scores, transfusion requirements and death rates than those in whom exploration with renal salvage was possible. In no case was nephrectomy required as a complication of exploration or attempted repair. In the properly staged patient undergoing surgery for appropriate indications with early vascular control exploration of renal injuries is safe. It is not the exploration that results in the nephrectomy but the injury itself. PMID- 7861496 TI - Urological evaluation of adult renal transplant recipients. AB - We retrospectively reviewed the charts of 150 consecutive patients who underwent renal transplantation at our institution in 1990 to determine the effectiveness of our pre-transplantation urological evaluation. Of 100 patients who met the inclusion criteria 74 were evaluated solely with a history and physical examination, urinalysis and a urine culture, while the other 26 underwent additional tests because of either a history of urological problems or abnormalities at the initial evaluation. Urological complications occurred in 18 patients. In 10 patients the complications were related to the operation and included postoperative hematuria from bleeding at the site of the ureteral reimplantation, symptomatic lymphocele formation and urinary fistula resulting from necrosis of the distal ureter. These complications could not have been anticipated by the pre-transplant evaluation. Urological complications in the other 8 patients were a febrile urinary tract infection (4), temporary urinary retention (2), hematuria and back pain requiring bilateral native nephrectomy (1), and lower tract obstructive symptoms (1 who eventually required transurethral resection of the prostate 15 months after transplantation). Only 1 of these complications might have been averted with more extensive preoperative testing and in none of these patients did the urological complication compromise allograft function. We conclude that most patients with end stage renal disease require only minimal evaluation before renal transplantation. More extensive evaluation is necessary only in patients with a strong history of urological disease or with abnormalities found during the basic examination. PMID- 7861497 TI - Urological aspects of renal transplantation. PMID- 7861498 TI - Multicentricity in renal cell carcinoma. AB - In the era of ultrasound and computerized tomography, when more than 50% of renal cell carcinomas are detected incidently, with a high proportion of small tumors, the standard treatment of radical nephrectomy in the presence of a normal contralateral kidney should be questioned. The main objection against conservative surgery for renal cell carcinoma has been the concern about satellite small renal cell carcinomas, which have been reported in 7% and 19.7% of 100 and 66 kidneys, respectively. We studied the incidence of multicentric neoplasms in 50 kidneys: 27 with renal cell carcinoma and 23 autopsied normal kidneys. The incidence of small renal cell carcinoma in the kidneys with a tumor was 11.1% and that of small nodules in normal autopsied kidneys was 13% (none of them was malignant). The incidence of satellite malignant nodules in patients with renal cell carcinoma 3 cm. or smaller was 3.7% in our series, and 0% and 3% in other series. Therefore, patients who undergo nephrectomy for tumors up to 3 cm. in diameter may be considered as overtreated in 96 to 100% of the cases. We conclude cautiously that partial nephrectomy should be widely accepted in patients with small renal carcinoma and in the presence of a normal contralateral kidney. PMID- 7861499 TI - Electrohydraulic versus pneumatic disintegration in the treatment of ureteral stones: a randomized, prospective trial. AB - The efficacy and safety of electrohydraulic versus pneumatic lithotripsy in the treatment of ureteral stones were evaluated in a prospective, randomized study. A total of 72 patients with stones not capable of passing spontaneously and unsuitable for extracorporeal shock wave lithotripsy was randomized to either method (34 to electrohydraulic lithotripsy and 38 to pneumatic lithotripsy). While both techniques were equivalent in efficacy (85.3% for electrohydraulic and 89.5% for pneumatic lithotripsy), the perforation rates were significantly different (17.6 versus 2.6%, respectively). Although the long-term results revealed no significant differences, pneumatic lithotripsy, as the markedly safer and easier to handle technique, is currently the method of choice at our stone center for ureteral calculi requiring treatment but not suitable for extracorporeal shock wave lithotripsy. PMID- 7861500 TI - The changing management of ureterovaginal fistulas. AB - A retrospective review of 20 ureterovaginal fistulas in 19 patients treated within the last 20 years was done. All fistulas developed after gynecological procedures. The ureterovaginal fistulas resolved in all 7 patients in whom a self retaining internal stent was placed in either a retrograde (5) or antegrade (2) manner for a minimum of 4 to 8 weeks. In contrast to the literature, it is concluded that modern endourological treatment will result in resolution of a ureterovaginal fistula if passage of a suitable internal stent is feasible. Every effort should be made to treat a ureterovaginal fistula endourologically rather than resort to an open operation. PMID- 7861501 TI - Activation of bladder mast cells in interstitial cystitis: a light and electron microscopic study. AB - Interstitial cystitis, a sterile bladder condition, is characterized by urinary frequency, urgency, burning and suprapubic pain. Increasing evidence indicates that interstitial cystitis is a heterogeneous syndrome that reflects an immune response to a variety of triggers. More than 50% of the patients have allergies, 30% have the irritable bowel syndrome and almost 20% suffer from migraine headaches. Increased numbers of mast cells have been reported in interstitial cystitis. Mast cell activation, which is critical if these cells were to be implicated in this syndrome, has been investigated by electron microscopy, which definitively shows mast cell secretion. Recently, methylhistamine, the major metabolite of histamine, and the specific mast cell marker, tryptase, were shown to be significantly elevated in urine of interstitial cystitis patients. Bladder biopsies from 53 patients were analyzed blindly for the number and degree of activation of mast cells using 4 different stains for light microscopy, as well as electron microscopy. Controls included 16 patients with incontinence and chronic bacterial cystitis. Mast cells in controls were less than 10/mm.2 and were all nearly intact. Surprisingly, mast cells from 11 cancer patients averaged 50/mm.2 but almost all were intact. In contrast, mast cells from 26 interstitial cystitis patients averaged 40/mm.2 and more than 90% were activated to various degrees. Therefore, bladder mast cell activation is a characteristic pathological finding in at least a subset of patients with interstitial cystitis. PMID- 7861502 TI - Prevention of hemorrhagic cystitis following allogeneic bone marrow transplant preparative regimens with cyclophosphamide and busulfan: role of continuous bladder irrigation. AB - High dose cyclophosphamide and/or busulfan conditioning treatment of recipients of bone marrow transplants proved to be highly effective but associated with substantial and sometimes life threatening hemorrhagic cystitis. To prevent this complication, a prophylactic continuous bladder irrigation program was instituted in patients receiving cyclophosphamide and/or busulfan in preparation for bone marrow transplantation. Retrospective analysis of 199 patients who underwent allogeneic bone marrow transplantation revealed that continuous bladder irrigation significantly decreased the frequency of hemorrhagic cystitis in patients receiving busulfan and cyclophosphamide (continuous bladder irrigation 23% versus no bladder irrigation 53%, p < 0.004). There was no difference in the frequency of hemorrhagic cystitis between the different preparative regimens in patients who underwent continuous bladder irrigation. There was no relationship between the incidence of hemorrhagic cystitis and the severity of graft-versus host disease or the time to engraftment. The duration of hemorrhagic cystitis and overall survival rates were similar in both groups, and there was no increase in complications related to catheterization. In general, continuous bladder irrigation was well tolerated, decreased the incidence of hemorrhagic cystitis and may be useful in bone marrow transplant patients. PMID- 7861503 TI - Biofeedback for the treatment of stress and urge incontinence. AB - Biofeedback and pelvic floor electrical stimulation are new modalities that have been advocated for the treatment of urinary incontinence. To evaluate the long term effectiveness of biofeedback and identify factors predictive of a positive outcome, we prospectively studied 28 patients with stress and urge incontinence. All patients were evaluated with a complete history, physical examination, urinalysis and culture. Of 28 patients 21 were also studied with video urodynamics. Biofeedback was performed with the InCare PRS 8900* machine with each patient undergoing at least 6 office sessions. Quantifiable symptoms, such as frequency, nocturia and urgency, were evaluated before and periodically after treatment. Patients also graded the overall treatment response on a scale of 0 to 3. Biofeedback successfully treated 5 of 14 patients (36%) with stress incontinence and 9 of 21 (43%) with urgency incontinence. Treatment response was durable throughout followup in all responding patients. Additionally, there was a statistically significant decrease in daytime frequency and nocturia following biofeedback (p = 0.038 and p = 0.044, respectively). No pretreatment factors predictive of a positive outcome could be identified. Improvement in perineal muscle tone with time approached statistical significance. We conclude that biofeedback is a moderately effective treatment for stress and urge incontinence, and should be offered to patients as a treatment option. Few patients, however, choose biofeedback as a primary mode of therapy and, due to the availability of other highly successful treatments for stress urinary incontinence, it is unlikely to become a popular treatment option. PMID- 7861504 TI - Fascial sling for the management of urinary incontinence due to sphincter incompetence. AB - The surgical management of urinary incontinence due to sphincter incompetence is still a challenging issue for urologists to date. We reviewed our experience with the fascial sling performed in 10 male and 3 female patients 3 to 72 years old (median age 13 years) with sphincter incompetence, including 11 with a neurogenic bladder (8 with myelodysplasia, 2 after pelvic operation and 1 after spinal cord injury), 1 after transurethral resection of the prostate and 1 after surgical injury to the bladder neck. Patient selection for a sling procedure was based on cystography (an open bladder neck) and urodynamic findings (underactive external urethral sphincter on electromyography and low maximum urethral closure pressure). A free graft of fascia was harvested from the rectus fascia in 8 patients and from the fascia lata in 5, and the fascial sling was placed around the bladder neck in 11 and the bulbous urethra in 2. Augmentation cystoplasty was performed concomitantly in 9 patients with poor bladder compliance (8 ileocystoplasty and 1 gastrocystoplasty). Postoperative followup ranged from 4 to 63 months (mean 36). Nine patients became continent and 3 improved significantly but remain damp. Of these 12 patients 10 with a neurogenic bladder were placed on intermittent catheterization, while the 2 without a neurogenic bladder are able to void normally. The remaining patient with surgical failure due to inadvertent wound infection received an indwelling urethral catheter. In all but this patient preoperative and postoperative maximum urethral closure pressures were 34.3 +/- 5.7 and 37.2 +/- 3.8 cm. water, respectively, without a significant increase. However, postoperative simultaneous measurements of intravesical and intraurethral pressure demonstrated a dramatic increase in intraurethral pressure during coughing or straining because of the action of the sling. Postoperative upper urinary tract deterioration has not been documented to date. Although various surgical options have been available, the fascial sling seems to be promising in the management of refractory urinary incontinence due to sphincter incompetence. PMID- 7861505 TI - Urinary incontinence. PMID- 7861506 TI - Visually stimulated erection in castrated men. AB - Sexual interest and activity decrease following castration. We determined by objective criteria the erectile status of 16 men who were sexually active before castration for prostatic cancer. Castration was achieved by orchiectomy or hormonal manipulation. Patients answered a questionnaire regarding the medical status and erectile function before and after castration, and the blood level of testosterone was assessed. During viewing of an erotic videotape penile circumference and erection quality were monitored. Four patients (25%) achieved functional erection. Mean serum free testosterone levels in men who achieved erection were 1.125 +/- 0.362 pg./ml. (standard deviation) and 0.628 +/- 0.098 pg./ml. in those not achieving functional erection (p < 0.001). No statistically significant difference was noted in age, interval since castration, co-morbidity score or method of castration between the men who did and did not achieve erection. PMID- 7861507 TI - Corpus cavernosum electromyogram: spontaneous and evoked electrical activities. AB - Sympathetic skin responses recorded from the surfaces of limbs and the penis resemble the waveforms recorded by needle from the corpora cavernosa. Thus, corpus cavernosum electromyography might reflect a systemic sympathetic response rather than unique smooth muscle corporeal activity. We recorded electrical activity simultaneously from the corpora and limbs of 10 subjects. Spontaneous activity was unique to the corpora, while electrical activity in response to sympathetic activating maneuvers was found simultaneously in the corpora and limbs (Fisher's exact test, p < 0.001). It is concluded that 2 types of electrical activity can be recorded from the corpora--spontaneous activity, which might reflect specific smooth muscle activity, and response activity, which is part of the systemic response to sympathetic stimulation. PMID- 7861508 TI - Long-term results with penile vein ligation for venogenic impotence. AB - Penile vein ligation for venogenic impotence was performed on 15 patients between 1989 and 1992. Preoperative evaluation included color flow Doppler ultrasound, and dynamic infusion cavernosogram and cavernosometry with vasoactive substance injection. All operations were performed by 1 surgeon via an inguinoscrotal incision by excising the deep dorsal, cavernous and, if necessary, crural veins. All patients were interviewed using a structured telephone questionnaire from 19 to 45 months (mean 29) postoperatively. Postoperative potency was defined as erections sufficient for unaided coitus on more than 75% of attempts and was present in 9 patients (60%). The 2 failures had temporary improvement within the first 6 months. The only significant preoperative variable in assessing postoperative potency was the duration of erectile dysfunction before penile vein ligation: median 60 months (range 48 to 120) in the impotent group and median 24 months (range 12 to 168) in the potent group (p < 0.05, Mann-Whitney test). No correlation was found with systolic and diastolic arterial flow or resistive index as assessed by color flow Doppler evaluation, sites of leakage or patient age at operation. Similarly, no correlation was found with preoperative dynamic infusion cavernosometry maintenance rates. The most common complication was contracture of the penis in 6 patients (40%), although only 1 complained of a functional disturbance. We demonstrated favorable long-term results with an extensive venous ligation. While preoperative assessment with color flow Doppler ultrasound, dynamic infusion cavernosography and cavernosometry, and vasoactive substance injection establishes a diagnosis of corporeal veno-occlusive dysfunction, this evaluation provides no predictive indicators for successful outcomes in penile vein ligation. PMID- 7861509 TI - Inflatable penile implant infection: predisposing factors and treatment suggestions. AB - A retrospective review of 1,337 consecutive inflatable prosthesis implantations was done to detect predisposing factors for infection. Operations were performed by the same team during a 7-year period. Of the procedures 823 were primary implantations, while the remaining 514 were either revisions (mechanical failure, iatrogenic causes or patient dissatisfaction), salvage operations or removals for infection. The etiology of impotence as a predisposition for infection in primary implantations was significant for spinal cord injury (9% of the cases) and steroid use (50%). Diabetes had a statistically insignificant 3% risk of infection, with all other causes having a 1% infection rate. A total of 428 revisions was performed with an overall infection rate of 10%. Rates of infection ranged from 8% in nondiabetics to 18% in diabetics requiring revision. Staphylococcus species were the most commonly cultured organisms. Salvage operations (29 cases) of several types were attempted for infected prostheses. Our results with salvage were poor and we currently routinely remove the entire prosthesis for infection except in cases of urethral erosion of 1 cylinder. PMID- 7861510 TI - Peyronie's disease: surgical treatment based on penile rigidity. AB - Operative treatment of Peyronie's disease has the risk of penile shortening and/or loss of erection. To avoid these complications, we used plaque incision together with polytetrafluoroethylene (Gore-Tex) graft insertion in men with preserved penile rigidity and only implanted a penile prosthesis in men with erectile failure. Between August 1986 and July 1992, 24 men 36 to 72 years old (mean age 53 years) underwent surgery. Of the men 16 with adequate penile rigidity by history and/or RigiScan study, and severe curvature underwent plaque incision and polytetrafluoroethylene graft insertion. Eight men had erectile failure, including 4 with distal flaccidity as demonstrated by RigiScan study. These 8 men received a penile prosthesis (semirigid in 6 and inflatable in 2). In addition, 2 of these men also required plaque incision because of persistent curvature. With a mean followup of 47 months (range 20 to 92), all 16 men with incision and a polytetrafluoroethylene graft had excellent erections with satisfactory intercourse. Minimal curvature away from the plaque incision site, not causing any difficulty with sexual performance, occurred in 7 patients. The men with a penile prosthesis engage in normal intercourse without residual or recurrent curvature. Incision of Peyronie's plaque and polytetrafluoroethylene graft insertion is associated with an excellent functional result in men with normal preoperative penile rigidity. A penile prosthesis should be reserved for men with erectile failure. PMID- 7861511 TI - Corpus cavernosum: more confusion or more understanding? PMID- 7861512 TI - Urinary schistosomiasis associated with hepatitis C virus infection. AB - We studied 26 adult patients referred for cystoscopy: 13 consecutive patients with schistosome ova on bladder biopsy and antibodies to Schistosoma species in serum were classified as having urinary schistosomiasis, while 13 consecutive patients without schistosome ova on bladder biopsy and who were negative for antibodies to Schistosoma species in serum served as controls. Nine of 13 patients (70%) and none of 13 controls (p < 0.0005) had antibodies to hepatitis C virus in serum (anti-hepatitis C virus). All controls and patients who were negative for anti-hepatitis C virus had normal serum alanine aminotransferase levels, while 2 of 9 (22%) positive for anti-hepatitis C virus had elevated levels. Our study shows that patients with urinary schistosomiasis are at high risk for anti-hepatitis C virus positivity and that some of them may have active liver disease. Therefore, it is imperative to screen patients with urinary schistosomiasis for associated hepatitis C virus infection and liver disease. PMID- 7861513 TI - Percutaneous antegrade endopyelotomy: review of 50 consecutive cases. AB - Between 1988 and 1993, 50 percutaneous antegrade endopyelotomies were performed for ureteropelvic junction obstruction at this institution. The success of the procedure was based on radiological parameters as well as patient symptomatology. The overall success rate of the procedure was 88%. Endopyelotomy was successful in 9 of 11 patients (82%) who presented after failing previous renal procedures. When endopyelotomy was used as the initial treatment modality the success rate was 90%. These results support the argument that endopyelotomy should be considered as first line therapy for most adults with ureteropelvic junction obstructions [corrected]. PMID- 7861514 TI - Laparoscopic simultaneous ligation of internal and external spermatic veins for varicocele. AB - The conventional treatment of varicocele consists of interruption of reflux in the internal spermatic vein either by open retroperitoneal high ligation, an open inguinal approach or percutaneous embolization. Recently, high ligation of the internal spermatic vein has been performed via laparoscopy. We previously suggested that ligation of the internal spermatic vein alone is not adequate, and a comparative study has shown that our method of trans-inguinal ligation of the internal and external spermatic (cremasteric) veins yields better surgical results. A laparoscopic version of this operation is described, which was performed in 25 patients for 31 ligations (6 bilateral cases). Short-term results (followup at 3 months) have shown that the procedure is safe and effective (no complications, 24-hour hospitalization and 1 case of persistence due to a technical error). This procedure seems to be an attractive alternative to our trans-inguinal combined approach especially if bilateral ligation is necessary. PMID- 7861515 TI - Transperitoneal marsupialization of lymphoceles: a comparison of laparoscopic and open techniques. AB - This 2-center study compares the relative merits of laparoscopic and open surgical internal marsupialization of pelvic lymphoceles. Laparoscopic lymphocelectomy was performed in 12 patients (group 1). The results were compared with open lymphocelectomy performed in 13 contemporary patients (group 2) as well as 13 historical patients (group 3). Operative time was longer in group 1 compared to groups 2 and 3 (194.6 versus 176.9 versus 133.8 minutes, respectively). However, group 1 had a decreased blood loss (23.1 versus 74.6 versus 61.7 ml.), earlier resumption of oral food intake (0.9 versus 2.5 versus 2.1 days), shorter hospital stay (2 versus 6.1 versus 6.3 days) and abbreviated convalescence (2.2 versus 6.9 versus 4.5 weeks) compared to groups 2 and 3. Complications included cystotomy requiring open repair in 1 patient in group 1, prolonged ileus in 1 in group 2, transection of the ureter of a transplant kidney in 1 in group 3 and pneumonitis in 1 in group 3. Lymphocele recurred in no patient in group 1, 4 in group 2 and 3 in group 3. Mean followup in groups 1 to 3 was 12.8, 25 and 54.5 months, respectively. We conclude that laparoscopic lymphocelectomy is effective, results in minimal patient morbidity and allows for a more rapid recovery compared to open surgical lymphocelectomy. PMID- 7861516 TI - Minimally invasive therapy. PMID- 7861517 TI - Improved focusing for extracorporeal shock wave lithotripsy of ureteral calculi. AB - Extracorporeal shock wave lithotripsy of ureteral calculi, which is usually performed with the patient in the prone position, may be difficult or even impossible under certain conditions because x-ray visibility is poor or the calculus is out of range of the shock wave focus. Treatment conditions can be improved by a simple change in the positioning of the patient, using the shock wave head from the contralateral side. This method is applicable for the common Siemens Lithostar device. PMID- 7861518 TI - An alternative to manage a nondeflating Foley catheter in women. AB - The urologist is frequently called upon to remove a nondeflating Foley catheter. The basic strategies to accomplish removal involve relieving obstruction of the blocked balloon port channel, dissolving the rubber balloon chemically or rupturing the balloon percutaneously. A less invasive technique of balloon rupture in the female patient, using a peri-catheter urethral route, is described. PMID- 7861519 TI - Spontaneous ureteral stent fragmentation. AB - A series of spontaneous multiple fragmentations of 3 ureteral stents presenting with a variety of clinical features is reported. Physical analysis measuring the tensile mechanical properties was done of the retrieved fragments together with 2 new stents, as well as electron microscopy scanning of the retrieved fragments. This methodology in evaluating fractured stents is unique in its capability to determine the accelerated aging process of stent material and to our knowledge has not been reported previously in this context. The retrieved catheters were moderately incrusted. The tensile elongation (maximal elongation at break point), known to be a sensitive indicator of the aging process of plastic materials, was dramatically decreased in the retrieved stents. The fractures in all catheters retrieved as well as in the new stents were found to pass exclusively through the side holes. Fragmented catheters had a distinctive electron microscopic appearance and physical properties, which may be defined in a systematic manner and may contribute to further refinement of stent quality. PMID- 7861520 TI - Fungal infections of the perivesical space. AB - We describe 3 patients with fungal infection in the perivesical space who manifested lower abdominal pain and urinary tract symptomatology. Imaging studies demonstrated perivesical abnormalities. Urine culture was positive for fungus in only 1 patients. Management required surgical exploration, drainage, debridement of necrotic tissue and in 1 patient partial bladder resection. Systemic antifungal therapy was administered postoperatively. All patients had a successful outcome. PMID- 7861521 TI - Intraperitoneal bladder rupture after normal vaginal delivery. AB - To our knowledge we report the first case of bladder perforation in a patient with no history of pelvic surgery or delivery. The patient presented 3 days post partum with renal failure and ascites. Paracentesis and cystography confirmed urinary ascites and bladder rupture. After open bladder repair convalescence was uneventful. The literature on intraperitoneal bladder rupture and urinary ascites is reviewed. PMID- 7861522 TI - Glomerulations in women with urethral sphincter deficiency: report of 2 cases [corrected]. AB - A classic feature of interstitial cystitis is the development of glomerulations during bladder distention while the patient is under anesthesia, which is thought to be a sign that the bladder was chronically under filled before distention. The cause for under filling is pain or sensory urgency in interstitial cystitis, and glomerulations have also been associated with conditions of decreased functional bladder capacity. Two cases of bladder glomerulations associated with severe intrinsic urethral sphincter deficiency (type 3 incontinence) are reported. Neither patient had symptoms of interstitial cystitis before or after anti incontinence surgery. A likely explanation is that severe stress incontinence chronically prevented the bladder from filling to capacity before cystoscopy. Thus, these cases support the premise that glomerulations are a response to distending a previously under filled bladder [corrected]. PMID- 7861523 TI - Acquired rectourethral fistula: methods of repair. AB - Rectourethral fistulas are a rare but devastating complication of urinary or rectal surgery, trauma or inflammation. Historically repair has posed a challenge because of technical difficulties and the high incidence of recurrent fistulas. We report 7 cases of acquired rectourethral fistulas of varying etiology (3 after prostatectomy, 3 after trauma and 1 after recurrent perineal abscess), which were managed by various means. Our data and those in the literature suggest that the first attempt at repair is the best and subsequent repairs become increasingly difficult; the York Mason approach allows easy accessibility with minimal risk of complications and the best chance for a functionally successful outcome when a vascularized flap is not required, and some cases may have such a low probability of successful resolution of the fistula as well as maintenance of urinary continence that cystectomy and supravesical diversion are appropriate considerations. PMID- 7861524 TI - Posttraumatic high flow internal pudendal artery-urethral fistula. AB - A case of posttraumatic fistula of the internal pudendal artery-urethra is reported. The patient was referred with prolonged pulsatile gross hematuria requiring multiple blood transfusions after a motor vehicle accident. Associated injuries included a comminuted pubic ramus fracture. Initial uroradiographic evaluations did not identify the site of origin of hematuria but eventually selective angiography allowed diagnosis. Selective arterial embolization of the internal pudendal artery provided definitive treatment. PMID- 7861525 TI - Spontaneous corporeal herniation of the penis: a new abnormality of the tunica albuginea? AB - A 63-year-old man presented with a penile mass present only during erections. Radiographic evaluation suggested a vascular lesion but the only abnormality identified at exploration was local attenuation of the tunica albuginea with aneurysmal dilatation of the corpora cavernosa. We believe this to be the first report of spontaneous herniation of the tunica albuginea of the penis. The possible etiology of this disorder is discussed. PMID- 7861526 TI - Preputial necrosis as an unusual cutaneous manifestation of cholesterol crystal embolization. AB - We report a case of the cholesterol crystal embolization syndrome concomitant with an unusual cutaneous localization. Extensive embolization of cholesterol crystals caused severe necrosis of the prepuce. Circumcision was performed and histopathological examination confirmed the diagnosis. PMID- 7861527 TI - Histiocytoid hemangioma of the testis: a case report. AB - We report a rare case of testicular histiocytoid hemangioma. Pathological features and differential diagnosis of this neoplasm are discussed. PMID- 7861528 TI - Pyocele of the scrotum: a consequence of spontaneous bacterial peritonitis. AB - To our knowledge pyocele of the scrotum after spontaneous bacterial peritonitis has not been reported previously. We describe this unusual condition, and discuss diagnosis, pathophysiology and treatment. PMID- 7861529 TI - Prostatic aspergillosis. AB - Prostatic aspergillosis is rare with only 3 cases reported previously. We report a case of localized invasive aspergillosis of the prostate in a nonimmunocompromised patient with chronic urinary retention and recurrent urinary tract infections. Transurethral resection followed by open prostatectomy was performed for massive prostatomegaly. No systemic antifungal therapy was required for cure. The literature is reviewed, and diagnostic and management options are discussed. PMID- 7861530 TI - Re: Does a stage pT0 cystectomy specimen confer a survival advantage in patients with minimally invasive bladder cancer? PMID- 7861531 TI - Historical review of theories on testicular descent. PMID- 7861532 TI - The impact of prenatal sonography on the morbidity and outcome of patients with renal duplication anomalies. AB - Historically, most patients with a renal duplication anomaly associated with upper pole hydronephrosis underwent upper pole nephrectomy and partial ureterectomy. Prenatal sonography has resulted in increased recognition of these anomalies and, therefore, earlier urological referral and evaluation. We investigated whether as a result more upper pole moieties were preserved by performing alternative procedures, such as ureteroureterostomy. In addition, the impact on overall morbidity of the disease and its treatment is assessed. Since 1984, of 29 patients treated for ectopic ureter or ureterocele 13 presented initially with a diagnosis of prenatal hydronephrosis. Of these patients, 5 (38.5%) underwent a renal sparing procedure consisting of ureteroureterostomy in 4 and excision of ureterocele with common sheath ureteral reimplantation in 1. The remaining 8 patients underwent upper pole nephrectomy and partial ureterectomy for a nonfunctioning upper pole moiety. In contrast, of 16 patients who presented without having undergone prenatal sonography only 2 (12.5%) underwent a renal preserving procedure. Initial treatment in the remaining 14 patients was upper pole nephrectomy and partial ureterectomy. The average age at initial treatment in the prenatally detected group was 3 months, compared with 5 years in the other group. Only 1 of the 13 patients (8%) in the prenatally detected group had symptoms, whereas 14 of 16 in the other group (87.5%) presented with significant symptoms consisting of sepsis in 12, an abdominal mass in 1, urinary incontinence in 1, and an incidental diagnosis made during evaluation of an associated anomaly in 2. Although there is still controversy regarding the impact of prenatal detection of hydronephrosis on the preservation of renal function in patients with a single system, our results show a beneficial effect in patients with duplication anomalies. This was reflected in our ability to salvage the upper pole moieties 3 times more frequently than was previously possible with minimal morbidity. More importantly, the potential serious clinical manifestations of these duplication anomalies in later life were eliminated by virtue of early treatment. PMID- 7861533 TI - The Mitrofanoff catheterizable channel: patient acceptance. AB - A review of our experience with the Mitrofanoff catheterizable channel, with emphasis on patient acceptance and preference, is presented. Continent catheterizable channels using the Mitrofanoff principle were created in 35 patients (mean age 9.1 years, range 2 to 21). Mean followup was 22 months (range 1 to 60). Followup data are available for 33 patients. We used the appendix, ureter, fallopian tube and tube of stomach to construct the channel. All 33 patients used the Mitrofanoff catheterizable channel without difficulty for at least 3 months postoperatively. A total of 16 patients (48%) can empty the bladder only by Mitrofanoff catheterization and do so without difficulty. All 11 patients (33%) who have the potential to catheterize either the Mitrofanoff channel or urethra choose to catheterize the Mitrofanoff channel preferentially. The patient not using Mitrofanoff catheterization had stomal stenosis 12 months postoperatively and elected to perform urethral catheterization rather than undergo surgical repair. Five patients (15%) can void but all use the Mitrofanoff catheterizable channel to monitor post-void residual volumes. This study shows a high acceptance rate for patients receiving a continent catheterizable stoma. PMID- 7861534 TI - Sexual abuse: another causative factor in dysfunctional voiding. AB - Dysfunctional voiding is thought to be a learned disturbance. We report on 18 patients with onset of dysfunctional voiding after childhood sexual abuse. We believe that the possibility of sexual abuse should be considered in the evaluation of a child with new onset of voiding dysfunction or of an adult presenting with long-term voiding dysfunction. PMID- 7861535 TI - Sexual abuse and voiding dysfunction. PMID- 7861536 TI - Newborn penile glans amputation during circumcision and successful reattachment. AB - Circumcision, the most common operation in male patients in the United States, is performed by a variety of health care professionals. Although not technically difficult, it results in a large number of reported and unreported complications annually. We report the successful reattachment of a distal penile glans, which was amputated when the Sheldon clamp was used for newborn circumcision. The literature is reviewed, and prevention and treatment of this type of circumcision injury are described. PMID- 7861537 TI - Impaired germ cells in secondary cryptorchid testis after herniotomy. AB - Secondary cryptorchidism was investigated after hernia repair in 15 patients 1 month to 7 years old. Testicular biopsy was obtained during orchiopexy. The number of spermatogonia per tubular cross section was higher in these patients than in boys with primary cryptorchidism, and the differences were significantly greater when the period of cryptorchidism was longer than 5 years. Loss of germ cells in secondary cryptorchidism was lower than in primary cryptorchidism. The spermatogonia per tubular cross section ratios were at the same low level in both groups in adolescence. These differences between primary and secondary cryptorchidism can be due to a lack of testicular exocrine function after a normal priming effect when the testes are in descended position. Collagenization of the peri-tubular connective tissue and the lack of germ cells are the only histological changes that occur in secondary cryptorchid testes when they have remained in cryptorchid position for 2 years, which is in marked contrast to primary cryptorchid testes that did not receive the priming effect in the first months of life. However, fertility is influenced minimally due to the presumably normal functioning of the contralateral testicle. Secondary cryptorchid testes demonstrate significant dysfunction after 5 years in that position. Germ cell loss occurs more slowly in secondary than in primary cryptorchidism. Despite the optimistic prognosis for fertility, we recommend early orchiopexy for secondary cryptorchidism to prevent exocrine insufficiency of the affected testicle. PMID- 7861538 TI - Management of suspected antenatal torsion: what is the best strategy? AB - Currently, management of the newborn with suspected antenatal torsion is somewhat controversial. Many surgeons recommend early surgical exploration within the first few days of life, primarily to avoid errors in diagnosis. However, since the surgical and general anesthetic risks at this age are increased, it might be preferable to defer an operation until risks to the patient are minimized. The optimal solution to this dilemma would be the ability to diagnose torsion and exclude other conditions noninvasively. We present a series of 12 patients 1 to 14 days old who presented with a scrotal mass secondary to suspected antenatal testis torsion. Color Doppler ultrasound in each case demonstrated abnormal testicular blood flow and architecture consistent with testis torsion. Eventual exploration of all 12 patients confirmed prenatal torsion. We conclude that scrotal ultrasound with color Doppler enhancement can accurately identify neonates with antenatal testis torsion and exclude other scrotal pathological conditions. If elected, surgery for torsion can then be deferred until the risks of anesthesia and surgery are improved. PMID- 7861539 TI - Transrectal posterior sagittal approach to prostatic utricle (mullerian duct cyst). AB - We describe use of the posterior sagittal trans-anorectal approach to excise a prostatic utricle in a child. This alternative approach provides excellent exposure to the retrourethral space, permitting safe and functional reconstruction. PMID- 7861540 TI - Technical considerations in the repair of cloacal vaginal deformities. AB - Various techniques of vaginal repair used in the reconstruction of cloacal deformities are discussed. In 4 years we performed primary reconstruction of cloacal anomalies in 4 children, 3 of whom had hydrocolpos and 1 vaginal agenesis. Vaginal reconstruction was done using a variety of techniques tailored to the primary anomaly. Distal vaginal occlusion related to ischemia occurred in 2 patients and in both the vagina was successfully reconstructed at a second stage procedure. Overall cosmetic and functional results were good. All patients are dry but require clean intermittent catheterization and 3 currently require a bowel regimen at followup of 18 months to 4 years. PMID- 7861541 TI - Postoperative adhesion formation after urological laparoscopy in the pediatric population. AB - The risk of intraperitoneal adhesion formation is a concern with transperitoneal laparoscopic surgery. To evaluate the incidence of adhesions after interventional urological laparoscopy, we reviewed 41 pediatric patients who had undergone second-look procedures. The number of adhesions and quantitation of the degree of each adhesion were assessed. Major laparoscopic procedures were performed previously in 8 patients, moderate in 29 and minor in 4. Adhesions were noted in 4 patients (9.8%), including 2 adhesions at the operative site and 2 at trocar sites. The risk of adhesions increased with the extent of dissection. Two adhesions developed after major procedures but the grade and extent of these adhesions were minimal. In the majority of patients re-peritonealization occurred with minimal or no scarring noted. Although adhesions may occur with pediatric urological laparoscopic procedures, the incidence appears lower than what one would expect with open exploration. PMID- 7861542 TI - Immunohistochemical localization of glucose transporters in human renal cell carcinoma. AB - The localization of 2 isoforms of glucose transporters (GLUT1 and GLUT4) in 75 patients with renal cell carcinoma was examined immunohistochemically. Paraffin sections were immunostained with either anti-GLUT1 or GLUT4 antibody by the avidin-biotin-peroxidase complex method. In 55 of 75 patients, GLUT1 staining was demonstrated at the plasma membrane of the cancer cells. In the clear cell subtype, 44 of 52 (84.6%) patients were positive for GLUT1. We did not detect positive staining for GLUT1 in the spindle cell type. In the mixed cell subtype, positive staining was recognized in only the areas of clear cell carcinomas (10 of 13; 76.9%). Positive staining for GLUT1 did not show any significant correlation with tumor grade or extent. Heterogeneous expression of GLUT1 was observed in tumor cell mass: some tumor cells were positive for GLUT1, while other cells were not. In adjacent normal tissue, GLUT1 staining was only recognized at the plasma membrane of some renal tubules. GLUT4 staining was not recognized in either tumor or normal tissues. PMID- 7861543 TI - Biodistribution and phototoxicity of 5-aminolevulinic acid-induced PpIX in an orthotopic rat bladder tumor model. AB - 5-Aminolevulinic acid (ALA) is a precursor of heme biosynthesis. In the penultimate step of this biosynthesis, protoporphyrin IX (PpIX), an effective photosensitizer, is generated. In this study, the biodistribution and photodynamic effect of ALA-induced PpIX were investigated in an orthotopic rat bladder tumor model. A quantitative comparison of PpIX biodistribution by extraction and fluorescence spectroscopy following intravenous and intravesical administration of ALA was made. The tumor to normal bladder wall ratio was 2:1 at 4 hours for both delivery modes. Fluorescence microscopy demonstrated predominantly cellular rather than stromal PpIX fluorescence. Phototoxicity, evaluated 4 hours after ALA administration, was light dose-dependent with the most efficient tumor necrosis being observed upon 150 J/cm.2 of 630 nm. irradiation. These data suggest that optimized photodynamic therapy with ALA induced PpIX may be an alternative treatment for superficial bladder carcinoma. PMID- 7861544 TI - Modulation of vasoactive intestinal polypeptide (VIP)-mediated relaxation by nitric oxide and prostanoids in the rabbit corpus cavernosum. AB - The polypeptide VIP has been proposed as an inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter involved in the relaxation of cavernosal smooth muscle during erection. However, the specific mechanism(s) by which VIP exerts its effect is unknown. To determine whether VIP is involved in NANC mediated cavernosal relaxation, strips of corpus cavernosum from New Zealand White rabbits were hung in tissue baths; atropine and guanethidine were added to block cholinergic and adrenergic neurotransmission, respectively. The tissue was then submaximally precontracted with norepinephrine (NE) and relaxed by electrical field stimulation (EFS; 10 V square waves, 0.5 msec. duration, 10 second trains at 5, 15 and 40 Hz) before and after preincubation with the VIP antagonist, VIP 10-28. To evaluate the role of nitric oxide (NO) and prostaglandins on the relaxant effect of VIP in the corpus cavernosum, the strips were contracted with NE and subsequently relaxed with cumulative doses of VIP (10(-10) to 10(-6) M.). After VIP dose-response curves were obtained, the strips were preincubated with N omega-nitro-L-arginine (NOARG, an inhibitor of nitric oxide synthase, 10(-4) M.) and the VIP dose-response curve was repeated. Indomethacin (10(-5) M.) was added to one-half of the NOARG treated strips to inhibit prostaglandin synthesis. VIP 10-28 inhibited EFS-induced relaxation (p < 0.05) and produced dose-dependent relaxation, which was inhibited by NOARG (p < 0.05). In contrast, the VIP-induced relaxation was more pronounced in the presence of indomethacin (p < 0.05). Moreover, indomethacin substantially reversed the NOARG inhibition of VIP relaxation (p < 0.05). These results suggest that VIP is a mediator of NANC cavernosal relaxation and that NO synthesis is involved in VIP-induced NANC relaxation in the corpus cavernosum. In addition, the presence of vasoconstrictive prostanoids modulates this VIP-mediated NANC relaxation. Therefore, VIP appears to contribute to NANC neurally mediated cavernosal relaxation, and its mechanisms of relaxation are dependent on prostanoid and involve the generation of NO. PMID- 7861545 TI - Deposition of calcium phosphate and calcium oxalate crystals in the kidneys. AB - Calcium phosphate (CaP) and calcium oxalate (CaOx) are the two most common crystalline constituents of human urinary stones. Calcium phosphate is often recognized as the nucleator of CaOx crystals, but the relationship between the two is not yet clearly understood. Using rat models of nephrolithiasis, we studied the role of CaP in renal deposition of CaOx. Calcium oxalate nephrolithiasis was brought about by inducing hyperoxaluria, while CaP CaOx nephrolithiasis was produced by dietary manipulation. Under similar urinary CaOx or CaP supersaturations, male rats were prone to form CaOx deposits while female rats were susceptible to produce CaP deposits in their kidneys. Crystal deposition in females was generally localized to the corticomedullary junction and in males to the renal papillae. The results indicate that gender plays an important role in the type and location of crystal deposition in the kidneys. In addition, deposition of CaP does not appear to influence the deposition of CaOx. PMID- 7861546 TI - An analysis of the Maxi-K+ (KCa) channel in cultured human corporal smooth muscle cells. AB - Previous studies have demonstrated that cultured corporal smooth muscle cells have prominent outward K currents composed of several different K channel subtypes. The goals of the present investigation were (1) to assert the nature of these channels and to evaluate the characteristics of the most predominant of these channel subtypes, the Maxi-K+ (KCa) channel, and (2) to compare KCa channel behavior in cultured corporal smooth muscle cells derived from the human corpus cavernosum of two distinct patient populations. The patient population was subdivided into two broad diagnostic categories: Group 1: 4 patients without evidence of organic disease of the corpus cavernosum, 3 of whom had documented erections; and Group 2: 4 patients with organic erectile dysfunction. Consistent with previous observations, 3 different K channel subtypes were detected in both patient populations, with corresponding conductances of 180, 100 and 40 pS, respectively. The approximately 183 pS channel was identified as the KCa channel based on its selective permeability to K+ and the fact that its open probability was modulated by both membrane potential and intracellular calcium levels. Specifically, the relative permeability of the 183 pS KCa channel to K+, Rb+, and NH4+ was 1.00:0.64:0.46. The channel was virtually impermeable to Na+ and Li+ (relative permeability < 0.02). In addition, the KCa channel was responsible for more than 90% of the outward K+ current passed through the cell membrane when depolarized. Furthermore, pharmacological studies using the K channel blocker tetraethylammonium ion (TEA) revealed that the sensitivity of KCa channels to TEA inhibition (as judged by the [TEA] required to block one-half of the outward whole cell current induced by a 90 mV depolarizing pulse) in cells from Group 1 patients was 1.05 +/- 0.22 mM. (n = 10 cells), while in sharp contrast the observed value for cells from Group 2 patients was 12.7 +/- 3.8 (n = 9 cells). The difference between the two groups was highly significant. These observations confirm and extend our previous studies to suggest that the KCa channel plays an important role in corporal smooth muscle physiology and, moreover, that alterations in the function/regulation of KCa channels may be an important feature of organic erectile dysfunction. As such, altered KCa channel behavior may contribute to an impaired hyperpolarizing ability of corporal smooth muscle, possibly altering intracellular calcium homeostasis and, perhaps, corporal smooth muscle reactivity and tone. PMID- 7861547 TI - PGE1 suppresses the induction of collagen synthesis by transforming growth factor beta 1 in human corpus cavernosum smooth muscle. AB - Collagen synthesis has been examined in primary cultures of human corpus cavernosum smooth muscle cells (HCCSMC), the major mesenchymal cell type of the corpus cavernosum. These cultures were grown from human surgical specimens and characterized by morphological and biochemical characteristics. These cells express mRNA for transforming growth factor-beta 1 (TGF-beta 1), a major regulator of extracellular matrix synthesis, as well as all three subtypes of TGF beta receptors. Human corpus cavernosum smooth muscle cells primarily synthesize types I and III fibrillar collagen. Treatment of HCCSMC with exogenous TGF-beta 1 (80 pM.) induced a 2.5- to 4.5-fold increase in the synthesis of types I and III collagen and resulted in detectable levels of type V/XI collagen. Treatment of HCCSMC with the eicosanoid PGE1 in combination with TGF-beta 1 suppressed the induction of collagen synthesis by TGF-beta 1 in a dose-dependent manner with concomitant decreases in types I, III and V/XI collagen. The expression of TGF beta 1 mRNA as well as types I and II TGF-beta receptors was induced by exogenous TGF-beta 1. Transforming growth factor-beta 1 mRNA induction was suppressed by PGE1. These data suggest that prostaglandins and TGF-beta 1 may play a key role in modulation of collagen synthesis in the corpus cavernosum, and in the regulation of fibrosis of the corpus cavernosum. PMID- 7861548 TI - The effect of antimicrobial therapy on testicular aspirate flow cytometry. AB - Many antibiotics have been shown to have adverse effects on spermatogenesis. Deoxyribonucleic acid (DNA) flow cytometry of testicular aspirate has been shown to be an effective method of quantitatively evaluating testicular function. To assess this problem, DNA flow cytometry of testicular aspirate was performed on 8 groups of rats, each of which received antibiotics via daily gavage for 10 days. Aspirations were performed on days 0, 11 and 56. Data thus obtained were analyzed using a two-way ANOVA with repeated measures. Antibiotics studies included ciprofloxacin 15 mg./kg./day, sulfamethoxazole (SMX) 20 mg./kg./day (with trimethoprim (TMP) 4 mg./kg./day), nitrofurantoin 7 mg./kg./day, ofloxacin 10 mg./kg./day, lomefloxacin 6 mg./kg./day, doxycycline 3 mg./kg./day and norfloxacin 10 mg./kg./day. One group received the same SMX/TMP dose, together with folate 0.014 mg./kg./day. A statistically significant change in aspirate content on day 11 as compared with baseline existed in groups receiving TMP/SMX (p = 0.00025), nitrofurantoin (p = 0.0000043), ofloxacin (p = 0.000075) and doxycycline (p = 4.89 X 10(-9). Control rats and the group receiving TMP/SMX with folate showed no significant change. On day 56 the abnormality persisted in groups TMP/SMX (p = 0.042), nitrofurantoin (p = 0.001), ofloxacin (p = 0.036) and doxycycline (p = 0.003). Controls and groups receiving ciprofloxacin, norfloxacin and lomefloxacin continued to show no statistically significant difference from baseline on day 56. These data suggest that SMX/TMP, nitrofurantoin, ofloxacin and doxycycline significantly alter spermatogenesis. Ciprofloxacin, norfloxacin and lomefloxacin had no apparent effect on spermatogenesis as measured by DNA flow cytometry. PMID- 7861549 TI - Impact of shock wave pattern and cavitation bubble size on tissue damage during ureteroscopic electrohydraulic lithotripsy. AB - It is known that electrohydraulic lithotripsy (EHL) during ureteroscopy may cause ureteral damage. To evaluate this trauma potential, find its mechanism and make it possible to avoid it, our research employed photographic evaluation, tissue studies, shock wave measurements and disintegration tests. The setup included a 3.3 F probe attached to an experimental generator with adjustable voltages and capacities providing energies from 25 mJ. to 1300 mJ. per pulse. In general, we distinguish between two traumatic mechanisms: (1) After placing the probe directly on the mucosa the rapid initial plasma penetrates the tissue resulting in a small, nonthermal, punched-like defect, whose depth depends on the energy applied. This trauma has minor clinical implications and is avoided by maintaining a minimum safety distance of 1 mm.; (2) According to physics, each plasma is followed by a cavitation bubble. The maximum size of this bubble depends on the energy applied and ranges from 3 mm. (25 mJ) to > 15 mm. (1300 mJ). In proportion to the bubble size, the ureteral wall may be distended or disrupted, even when the probe is not in direct contact with the mucosa. Therefore, the goal should be to obtain a low energy pressure pulse with high disintegration efficacy. Our evaluation of the pressure waves revealed that the selection of a high voltage and a low capacity leads to short and steep "laser like" pulses. These pulses have a significant higher impact on stone disintegration than the broader pulses of the same energy provided by currently available generators. PMID- 7861550 TI - Hypercalcemia and cosecretion of interleukin-6 and parathyroid hormone related peptide by a human renal cell carcinoma implanted into nude mice. AB - Humoral hypercalcemia of malignancy is a paraneoplastic syndrome believed to be due to production by the tumor of substances that stimulate osteoclastic bone resorption primarily. The human renal cell carcinoma cell line RC-8, grown in nude mice, was investigated for factors involved in renal cancer-induced hypercalcemia. At a tumor load of 200 to 400 mm.3 the mice developed hypercalcemia and hypophosphatemia associated with a rise in serum 1,25 dihydroxyvitamin D concentration and cachexia. The tumor released 1) significant amounts of human interleukin-6 (IL-6) and 2) parathyroid hormone-related peptide (PTHrP) into the circulation. Cancer cells further expressed mRNA for both human IL-6 and PTHrP. No secretion of human tumor necrosis factor-alpha or interleukin 1 beta could be demonstrated in the circulation of the host. Antibodies to IL-6 caused a significant (p = 0.043) inhibition of tumor growth and decreased serum calcium concentrations compared with control animals. Our data suggest that IL-6 is involved, either directly or indirectly, in the development of hypercalcemia in renal cell carcinoma. PMID- 7861551 TI - Inhibitory effect of dexamethasone and progesterone in vitro on proliferation of human renal cell carcinomas and effects on expression of interleukin-6 or interleukin-6 receptor. AB - Interleukin-6 (IL-6) has been suggested as an autocrine growth factor of human renal cell carcinomas. Since steroids are known to inhibit IL-6 gene expression, we investigated their effects on the growth of renal cell carcinoma. Dexamethasone inhibited proliferation of 2 of 4 renal cell carcinoma cell lines in a dose-dependent manner. In one of these 2 cell lines, IL-6 gene expression was also inhibited, but not in the other. The inhibitory effect of dexamethasone on cell proliferation was not reversed by the exogenous IL-6. In 1 of the 2 remaining cell lines, the inhibition of IL-6 gene expression was observed, although there was no inhibition of cell proliferation. Thus, inhibition of growth by dexamethasone did not correlate with an inhibitory action of dexamethasone on IL-6 mRNA expression. Progesterone inhibited the growth of 1 cell line without concomitant inhibition of IL-6 gene expression. Expression of IL-6 receptor mRNA was not altered. A dose-dependent increase in mRNA expression of gp130, the transducer of IL-6 signal, was induced by dexamethasone and progesterone in 2 and 1 of the 4 cell lines, respectively. These data suggest that, in some renal cell carcinomas, steroids may inhibit cell proliferation by a mechanism independent of their effects on mRNA expression of IL-6 and IL-6 receptors. Dexamethasone may be useful, not only for palliation of paraneoplastic syndrome caused by overproduction of IL-6, but also for inhibition of growth of renal cell carcinomas. PMID- 7861552 TI - AUA 90th annual meeting. Las Vegas, Nevada, April 23-28, 1995. Abstracts. PMID- 7861553 TI - The distribution of organs for liver transplantation. PMID- 7861554 TI - Directed to defend its raison d'etre, NIH holds communications conference. PMID- 7861555 TI - Latex-induced asthma among health care workers. PMID- 7861556 TI - Influenza vaccine first to reach immunization goal. PMID- 7861557 TI - From the Health Care Financing Administration. PMID- 7861558 TI - From the Centers for Disease Control and Prevention. Update: AIDS among women- United States, 1994. PMID- 7861559 TI - Centers for Disease Control and Prevention. Transmission of pertussis from adult to infant--Michigan, 1993. PMID- 7861560 TI - From the Centers for Disease Control and Prevention. Update: influenza activity- United States, 1994-95 season. PMID- 7861561 TI - From the Centers for Disease Control and Prevention. Human rabies--West Virginia, 1994. PMID- 7861562 TI - Cost of teaching medical students. PMID- 7861563 TI - Cost of teaching medical students. PMID- 7861564 TI - Case-mix adjustment: making bad apples look good. PMID- 7861565 TI - Effect of glycemic control on early diabetic renal lesions. PMID- 7861566 TI - Possible ocular adverse effects associated with leuprolide injections. PMID- 7861567 TI - Malaria in Somalia: lessons in prevention. PMID- 7861568 TI - Permissive hypercapnia: some equations. PMID- 7861569 TI - Fluorine concentration in drinking water and fractures in the elderly. PMID- 7861570 TI - Use of brand names in place of generics. PMID- 7861571 TI - Health system reform in the Republic of China. Formulating policy in a market based health system. PMID- 7861572 TI - The contribution of changes in the prevalence of prone sleeping position to the decline in sudden infant death syndrome in Tasmania. AB - OBJECTIVE: To determine the independent contribution of changes in infant sleep position to the recent decline in sudden infant death syndrome (SIDS) rate in Tasmania. DESIGN: (1) A comparison of the whole population incidence of SIDS before and after an intervention to reduce the prevalence of prone sleeping position. (2) A within-cohort analysis of the contribution of sleep position and other exposures to the decline in SIDS after the intervention. SETTING: Tasmania, Australia. PARTICIPANTS: (1) All SIDS cases from 1975 through 1992. (2) A sample of one in five infants born in Tasmania who at perinatal assessment were scored to be at higher risk for SIDS since January 1988. Of 5534 infants included in the study, 39 later died of SIDS. INTERVENTIONS: Multiple public health activities to reduce the prevalence of the prone infant sleeping position in Tasmania and verbal information on the association between prone position and SIDS to cohort participants from May 1, 1991. MAIN OUTCOME MEASURE: Sudden infant death syndrome incidence. RESULTS: The Tasmanian SIDS rate decreased (P < .01) from 3.8 (95% confidence interval [CI], 3.5 to 4.2) deaths per 1000 live births from 1975 through 1990 to a rate of 1.5 (95% CI, 0.9 to 2.2) deaths per 1000 live births in 1991 through 1992. The SIDS mortality rate in the cohort by period of birth was 7.6 (95% CI, 4.9 to 10.3) deaths per 1000 live births for those born from May 1, 1988, through April 30, 1991, and 4.1 (95% CI, 1.3 to 7.0) deaths per 1000 infants for those born from May 1, 1991, through October 31, 1992. The prevalence of usual prone sleeping position at 1 month of age was 29.9% and 4.3% in these two cohorts, respectively (adjusted odds ratio, 0.11; 95% CI, 0.08 to 0.13). Logistic regression demonstrated that 70% of the SIDS rate reduction in the cohort could be accounted for by the decreased prevalence of the prone sleeping position. Other factors examined individually contributed to less than 10% of the SIDS rate reduction. CONCLUSIONS: The major contributing factor to the recent SIDS rate decline in Tasmania has been the reduction in the proportion of infants usually sleeping prone. PMID- 7861573 TI - A case-control study of routine and death scene sleep position and sudden infant death syndrome in Southern California. AB - OBJECTIVE: To investigate whether infants who died of sudden infant death syndrome (SIDS) were routinely placed in different sleep positions compared with healthy infants in a multiethnic diverse population in the United States. DESIGN: A population-based case-control study. SETTING: Five counties in Southern California including Los Angeles, Orange, San Bernardino, Riverside, and San Diego. PARTICIPANTS: Parents of 200 white, African-American, Hispanic, and Asian infants who died of SIDS between January 1989 and December 1992 and parents of 200 healthy, living infants matched on the basis of birth hospital, birth date, race, and gender. Information was obtained from detailed telephone interviews with the parents and validated with obstetric and pediatric records. MAIN OUTCOME MEASURES: Routine sleep position, type of bedding, and objects in bed were determined for both case and control infants, while the last-placed and found sleep and face positions at death were reported for SIDS infants. RESULTS: Approximately 66% of SIDS infants and 64% of comparison infants routinely slept on their abdomens (P = .91). At the time of death, 80% of cases were found sleeping on their abdomens. There was no difference in routine sleep position for SIDS infants and comparison infants (odds ratio = 0.76; 95% confidence interval, 0.42 to 1.38), while simultaneously adjusting for birth weight (in grams), medical conditions at birth, breast-feeding, passive smoking, maternal recreational drug use, prenatal care, and infant vomiting. Hispanic parents routinely placed their infants on their abdomens less frequently than white parents (P < .01). However, the prone sleep position (face down) was the most commonly found sleep position at death in both Hispanic and non-Hispanic infants. CONCLUSIONS: Routine prone sleep position was not associated with an increased risk of SIDS in this study population. The results need to be confirmed with other parents of SIDS infants interviewed before the height of publicity regarding prone sleep position in the United States. PMID- 7861574 TI - The effect of passive smoking and tobacco exposure through breast milk on sudden infant death syndrome. AB - OBJECTIVE: To examine the relationship between sudden infant death syndrome (SIDS) and smoking during pregnancy; postnatal tobacco smoke exposure from the mother, father, live-in-adults, and day care providers; and postnatal smoke exposure from breast-feeding. DESIGN: Case-control study. SETTING: Five counties in Southern California. PARTICIPANTS: A total of 200 white, African-American, Hispanic, and Asian parents of infants who died of SIDS between 1989 and 1992 were compared with 200 control parents who delivered healthy infants. Case infants were matched to control infants on the basis of birth hospital, birth date, gender, and race. All information was obtained from a detailed telephone interview and validated with medical records. MAIN OUTCOME MEASURES: Risk of SIDS associated with passive smoking by the mother, father, live-in adults, and day care providers; smoking in the same room as the infant; total number of cigarettes smoked by all adults; and maternal smoking during the time period of breast-feeding. RESULTS: Conditional logistic regression resulted in overall adjusted odds ratios (ORs) for SIDS associated with passive smoke from the mother of 2.28, the father of 3.46, other live-in adults of 2.18, and all sources of 3.50 (95% confidence interval, 1.81 to 6.75), while simultaneously adjusting for birth weight, sleep position, prenatal care, medical conditions at birth, breast feeding, and maternal smoking during pregnancy. A dose-response effect was noted for SIDS associated with increasing numbers of cigarettes, as well as total number of smokers. Breast-feeding was protective for SIDS among nonsmokers (OR = 0.37) but not smokers (OR = 1.38), when adjusting for potential confounders. CONCLUSIONS: Passive smoking in the same room as the infant increases the risk for SIDS. Physicians should educate new and prospective parents about the risk of tobacco smoke exposure during pregnancy and the first year of the infant's life. PMID- 7861575 TI - Depot medroxyprogesterone acetate and breast cancer. A pooled analysis of the World Health Organization and New Zealand studies. AB - BACKGROUND: Although depot medroxyprogesterone acetate (DMPA) (Depo-Provera) has now been approved for marketing as a contraceptive in the United States, there are still unresolved issues about the relation between DMPA and risk of breast cancer. The two substantial case-control studies of this association yielded similar but inconclusive results. Because their designs were compatible, these studies were pooled to obtain more adequate data for analysis. DESIGN: Pooled results from two case-control studies. SETTING: New Zealand (entire country), Thailand (three centers), Mexico (one center), and Kenya (one center). PARTICIPANTS: A total of 1768 women with breast cancer and 13,905 controls, most of whom were younger than 55 years. MAIN OUTCOME MEASURE: Relative risk (RR) of breast cancer in women who had used DMPA. RESULTS: The RR of breast cancer for women who had ever used DMPA was 1.1 (95% confidence interval [CI], 0.97 to 1.4). There was no increase in risk with increasing duration of use of DMPA, but RR estimates were higher in certain subgroups of women. Further analyses suggested that recent (or current) use was the key factor, with women who had started using DMPA within the previous 5 years estimated to have an RR of 2.0 (95% CI, 1.5 to 2.8). CONCLUSIONS: The increased risk of breast cancer observed in recent (or current) users could be due to enhanced detection of breast tumors in women using DMPA or to acceleration of the growth of preexisting tumors. Women who had used DMPA more than 5 years previously had no increase in risk of breast cancer, regardless of their duration of use. PMID- 7861576 TI - The status of local smoking regulations in North Carolina following a state preemption bill. AB - OBJECTIVE: To determine the number and protectiveness of local smoking regulations adopted before the implementation of a preemptive statewide smoking control bill. METHOD: Review of local smoking control regulations from all 100 counties and 85 municipalities with populations greater than 5000 in North Carolina. MAIN OUTCOME MEASURES: Adoption of local smoking control regulations before and during the 3-month delay in enactment of the preemptive bill. Protectiveness of regulations was based on restrictions on smoking and requirements for separate ventilation systems at private work sites: none (smoking unrestricted); minimal (smoking restricted to designated areas); partial (smoking restricted to designated areas served by separate ventilation systems); and complete (smoking prohibited). Because some regulations would be phased in gradually over the next 5 years, we evaluated the requirements that will be in effect by January 1, 2000. RESULTS: Between July 15 and October 15, 1993, the number of local smoking regulations in North Carolina increased from 16 to 105. By the year 2000, 59% of private employees still will not be guaranteed any protection from work site environmental tobacco smoke; 19% will have minimal protection, 22% will have partial protection, and none will have complete protection. CONCLUSIONS: The 3-month delay in preemption created an unnatural time frame for communities to organize, debate, and adopt smoking restrictions. Despite the adoption of 89 new regulations, no private employees will be guaranteed complete protection from work site environmental tobacco smoke by the year 2000; new regulations can no longer be adopted. HB 957 has been a setback for public health in North Carolina. PMID- 7861577 TI - The rational clinical examination. Does this patient have a goiter? PMID- 7861578 TI - Sleep position and sudden infant death syndrome. PMID- 7861579 TI - Importance of nutrition in dialysis patients. PMID- 7861580 TI - Anti-neutrophil cytoplasmic auto antibodies (ANCA) in Pakistani patients with systemic vasculitides. AB - Anti-neutrophil cytoplasmic auto antibodies are directed against antigens in the neutrophil granules. Their detection by the indirect immunofluorescence clearly divides them into two distinct types, namely c-ANCA (Classical antineutrophil cytoplasmic antibody) and the p-ANCA (Perinuclear antineutrophil cytoplasmic antibody). These antibodies have been found to be useful as non-invasive markers to help establish the diagnosis in patients with systemic vasculitides. The antibodies also help in monitoring disease activity in some patients with systemic necrotising vasculitides. This study was aimed at demonstrating the utility of these auto-antibodies in the management of our patients presenting with systemic vasculitides. Fifty-six patients presenting with features of systemic vasculitides were examined over a six month period out of whom eight were found positive for these antibodies. The detection of these antibodies helped in early diagnosis and the institution of specific treatment. Six months follow-up in one patient with Wegener's granulomatosis, the disease activity related closely with the ANCA levels. PMID- 7861581 TI - Malignant tumours of the male breast--a review of 50 cases. AB - Carcinoma of breast is one of the less frequent malignancies in males. In this study 50 cases of malignant tumours of male breast diagnosed during a 10 years period (1980-1989) are analysed retrospectively. The malignant breast tumours in males were about 3% of all breast malignancies in both sexes and 0.34% of all types of malignant tumours diagnosed during the study period. One male breast was involved for every 33 female cases. The peak incidence was between 5th to 7th decade with mean age of 58.54 years. The mean duration of symptoms was 13.69 months and 46.15% cases reported to the hospital after one year of their symptoms. Clinically, a painless lump in the breast was most frequently seen, followed by ulceration of the skin. Histologically, the infiltrating duct carcinoma (grade III) was the predominant lesion and one case of Paget's disease of the breast was also seen. PMID- 7861582 TI - Nutritional assessment of patients on maintenance haemodialysis. AB - Nutritional assessment was carried out on fifty haemodialyzed patients by demographic, anthropometric, biochemical and dietary indices. The mean age of the patients was 49 years with a male to female ratio of 2.3:1. The duration of dialysis ranged from 6 to 40 months with a mean of 25 months. Fifty percent of the patients were moderately nourished based on their body weight 44%, body mass index 40% and mid-arm circumference 66%. Seventy percent patients had albumin and total proteins within the normal range. Blood urea nitrogen, creatinine, cholesterol, potassium and phosphorus did not significantly change from the previous reports. The calorie and protein intake in 60-70% cases was less than recommended. Overall there was a tendency to calorie and to a lesser degree protein malnutrition in our patients. It is suggested that preventing malnutrition by economical, aggressive and ongoing dietary intervention may minimize malnutrition in haemodialyzed patients. PMID- 7861583 TI - Management of tuberculosis by practitioners of Peshawar. AB - In this report the drug prescribing practices of practitioners are described. The results indicate that a high proportion (80%) of practitioners still prescribe long duration chemotherapy. The most frequently prescribed drugs are rifampicin (87%), isoniazid (89%) and streptomycin (73%). Despite the use of these highly effective drugs the duration of illness after diagnosis in 31% is over three years. The possible reasons for the poor control of the disease are noncompliance with treatment and multidrug resistance of mycobacterium tuberculosis. The prescribing practices of the practitioners indicate that they are not receiving continuing education and training on the case management of TB. PMID- 7861584 TI - Anaemia in children: Part I. Can simple observations by primary care provider help in diagnosis? AB - The commonest and reliable method of diagnosing anaemia is by determining haemoglobin levels, which is an invasive technique. This cross-sectional study aims to detect the validity of diagnosing anaemia by simple non-invasive clinical techniques. This study screened 951 children (6-60 months) residing in a squatter settlement of Karachi. Every child was first labelled anaemic or normal by a clinical scoring system and then his/her haemoglobin was tested by finger prick method on a Hemocue. Mean age was 31.1 +/- 15.3 months (n = 945) and median was 32 months. The prevalence of anaemia by Hemocue was 78% (Anaemia = Hb < 11 gms%) and by clinical examinations 68%. Conjunctivae alone had the highest sensitivity (74%) and nails alone highest specificity (96%). Nails alone had the highest positive predictive value and conjunctivae alone highest negative predictive value (43.2%). Combinations of conjunctivae with either nails, palm or tongue yielded the highest validity. The results indicate that in PHC settings with no laboratory facilities, anaemia can be detected by pallor of conjunctivae associated with pallor of either nails, palm or tongue. PMID- 7861585 TI - Anaemia in children: Part II. Should primary health care providers prescribe iron supplements by the observation and presence of assumed symptoms? AB - The dilemma of private practitioners is whether to prescribe or not to prescribe iron supplements on suspicion of anaemia. This cross sectional study was done in an urban squatter settlement with a primary health care centre to assess the significance of symptoms and a history of associated diseases in the diagnosis of anaemia. A total of 321 children were sampled from 1800 children < 5 years of age in a population of 11,000, by systematic random sampling. Mothers were asked about the presence of assumed associated symptoms and diseases which were listlessness, irritability, anaemia, pica, poor weight gain, diarrhoea, acute respiratory infection and malaria in last 3 months. There was significant association between anaemia (Hb < 11 gms%) and irriability (P < .02), anorexia for solid foods (P < .04), pica (P < .001), episode of diarrhoea (P < .001) and poor weight gain (P < .006). There was no significant association between malaria, cold, cough and anaemia. Children with these symptoms complex should receive iron supplements. PMID- 7861586 TI - Potability of water obtained through boring in Karachi. AB - This study was carried out to detect the faecal contamination in water obtained from indigenously designed boring facilities. The presence of escherichia coli (major indicator of faecal contamination) was detected after performing the coliform test along with biochemical studies in 32 boring water samples out of 60 samples collected from various localities of Karachi city. Its presence in underground water resources definitely indicates the possible presence of water borne pathogens. PMID- 7861587 TI - A study of pyuria, bacteriuria, nitriteuria to evaluate initial screening test for urinary tract infection. PMID- 7861588 TI - A study of snake bite cases. PMID- 7861589 TI - Progression of chronic renal disease--an update. PMID- 7861590 TI - Ileocaecal tuberculosis: a pictorial essay of various appearances on small bowel enema. PMID- 7861591 TI - Coincidence of acute amoebic appendicitis and enterobius vermicularis infestation. PMID- 7861592 TI - [A consideration on recent stasis in the progress of obstetric anesthesia]. PMID- 7861593 TI - [Evaluation of analgesic effects of morphine, buprenorphine and pentazocine in rats receiving somatic and visceral stimulation]. AB - The analgesic effects of morphine, buprenorphine and pentazocine examined by behavioral responses to tail-flick (TF) and colorectal distension (CD) were studied in rats. Animals were randomly divided into three groups; morphine (M) groups of 4 mg.kg-1 (n = 7), buprenorphine (B) groups of 0.03 mg.kg-1 (n = 8), pentazocine (P) groups of 3 mg.kg-1 (n = 8). After determinations of TF and CD values, animals were administered each analgesic intraperitoneally, and both procedures were repeated every 5 minutes until 40 minutes. Three drugs produced an almost same degree of increase in pain threshold for TF; % maximum possible effects (%MPEs) were approximately 30%. Similar patterns of increase in pain thresholds for CD were observed in M and B groups; %MPEs were approximately 20%. In contrast, P groups showed a significant increase in thresholds for CD compared to M and B groups; 20 minutes after intraperitoneal administration of P, %MPE was approximately 50%. These results indicate that there are different antinociceptive effects to somatic and visceral stimuli between M, B and P, and suggest that selective opioid agonists modulate responses to different kinds of noxious stimuli. PMID- 7861594 TI - [Effect of celiac plexus block and thoracic epidural block on arterial ketone body ratio]. AB - We evaluated the effect of intraoperative celiac plexus block (CPB) and thoracic epidural block (TEB) on arterial ketone body ratio (AKBR) in the patients undergoing total or partial gastrectomy. Mean arterial pressure (MAP), heart rate, AKBR, and arterial blood gas were measured at the end of esophago jejunostomy, gastro-duodenostomy, or gastro-jejunostomy (pre-block) and at the end of operation (post-block), respectively. After pre-block measurement, CPB with 99.5% ethanol 15-20 ml was carried out in 8 patients with advanced gastric cancer (CPB group); TEB with 2% lidocaine was performed on 8 patients (TEB group); and neither CPB nor TEB was done on 8 patients (control group). A significant reduction in MAP was observed after CPB and TEB. There was no difference in the degree of MAP decrease between CPB group and TEB group. No change in MAP was observed in control group. In CPB group significant decreases in AKBR, pH, and BE were induced by CPB. However, there were no difference in AKBR, pH, and BE between pre-block values and post-block values in TEB group as in the control group. These findings suggest that ethanol used in CPB reduces the redox state of hepatic mitochondria and increases lactate. Therefore we should pay attention to the changes in AKBR, pH, and BE after celiac plexus block with ethanol. PMID- 7861595 TI - [Hemodynamic responses to nitrous oxide during isoflurane anesthesia in humans]. AB - Isoflurane often produces tachycardia during clinical anesthesia. We examined the effect of a stepwise increase of isoflurane concentration on hemodynamic parameters in the absence or presence of nitrous oxide (N2O). After induction with thiamylal (3 mg.kg-1), isoflurane in oxygen or in 66% N2O-oxygen was administered with mask ventilation. Inspired isoflurane concentration was increased in a stepwise fashion (1, 2, 3 and 4%) every 5 minutes and manual ventilation was performed to maintain ETCO2 within 35-40 mmHg. Blood pressure (BP), heart rate (HR) and cardiac output (CO) were measured before and at every minute after isoflurane administration until 20 minutes. Systolic BP decreased gradually with increasing isoflurane concentration, but was transiently elevated for 3%. HR increased in a dose-related manner. CO decreased significantly at 1 3%. N2O and this seemed to magnify the isoflurane-induced decrease in BP and increase in HR at 1% and 2%. CO increased from baseline at 4%. Isoflurane tended to increase HR in a dose-related manner and induced a hyperdynamic response during rapid increasing of isoflurane concentration. This response may have beed caused by the irritating effect of isoflurane on the airways. Addition of N2O attenuated this response because it increases the speed of induction and the depth of anesthesia. PMID- 7861596 TI - [Significance of patient's position in measuring gastric contents]. AB - We evaluated the significance of patient's position in the measurement of gastric contents at the induction of anesthesia (n = 18). After the induction of general anesthesia with tracheal intubation, a nasogastric tube (16F) was inserted into the stomach. Presence of the tube within the stomach was verified by ausculation of injected air. Gastric fluid was aspirated with the patient supine and then in the right and left lateral decubitus positions. The existence of the gastric content which can not be aspirated with supine position was confirmed. We conclude that it is necessary to place the patient on bilateral decubitus positions besides supine to evaluate the volume of the gastric content correctly. PMID- 7861597 TI - [Effect of continuous infusion of flumazenil on unexpected postoperative resedation by midazolam]. AB - Resedation after general anesthesia induced by midazolam is thought to be not an unusual problem for the anesthetists. We investigated the effect of continuous infusion of flumazenil on the patients who had general anesthesia using midazolam as an induction agent and had flumazenil for prolonged recovery after procedure. Fourteen of 54 patients were judged as prolonged recovery and were given 0.25 mg of flumazenil. Then, they were randomly divided into the following two groups. In the first group, another 0.25 mg of flumazenil was given 2 hours after the first flumazenil. In the second group, 0.25 mg of flumazenil in 250 ml of lactated Ringer's solution was given continuously for 2 hours after the first flumazenil. All the patients were fully awake after the first flumazenil but one case of resedation occurred in the first group and in none of the patients in the second group. We conclude that continuous infusion of 0.25 mg of flumazenil for 2 hours is effective and makes anesthetist free from anxiety of postoperative resedation by midazolam. PMID- 7861598 TI - [Effects of pressure support ventilation (PSV) or PSV+PEEP on the respiratory function during general anesthesia under spontaneous ventilation]. AB - This study was performed to examine the hypothesis that PSV with PEEP compared to spontaneous breathing with a circle anesthesia system may have beneficial effects on gas exchange and work of breathing during inhalational anesthesia. Nine patients (age; 58 +/- 20 yr) scheduled to receive general anesthesia for orthopedic (n = 3) or ENT (n = 6) surgery were randomly assigned in a triple cross-over manner to breathe with a standard anesthesia circle system, 5 cmH2O PSV, and 5 cm H2O PSV above 5 cmH2O PEEP. General anesthesia was induced with thiamylal (5 mg.kg-1) and succinylcholine (1 mg.kg-1), followed by tracheal intubation. General inhalation anesthesia was maintained with 1% isoflurane and nitrous oxide in 40% oxygen. Patients were permitted to breathe spontaneously. A BiPAP-S Ventilatory Support System was connected to a standard anesthesia machine instead of a reservoir bag to deliver PSV or PSV with PEEP. Respiratory parameters were measured with a C-P 100 Pulmonary Monitor. After breathing for 20 minutes with the assigned mode, measurements and blood gas sampling were performed. Statistical analysis was performed with ANOVA. There were no statistical differences in PaO2 within the three groups (table). PaCO2 was lower during PSV+PEEP, but the difference was not significant. This level of PSV or PSV with PEEP may have little beneficial effects on gas exchange in our study condition. The mean WOBp was smaller in the PSV with PEEP group but the difference was not statistically significant. PMID- 7861599 TI - [Evaluation of the tolerance to hemorrhagic shock--comparison between hemodilution and non-hemodilution]. AB - We induced various degrees of bleedings in adult mongrel dogs to determine their tolerance to bleedings. The dogs were divided into two groups: the hemodilution group (Group A: Hct 11.1 +/- 1.9%) and the non-hemodilution group (Group B: Hct 36.8 +/- 6.6%). The Group A tended to show higher tolerance to bleedings than the Group B, although the difference was not significant. Throughout the period of increasing degrees of bleedings, MAP remained higher in Group B than in Group A, but CI was higher in Group A than Group B. DO2I was kept higher in Group B than in Group A. Both PaO2 and PaCO2 showed no difference between the two groups. The results of our study indicate that hemodilution group tends to be more tolerant to bleeding than non-hemodilution group. The reason is probably that under hemodilution the oxygen delivery is maintained through an increase in cardiac output in the presence of decreased arterial oxygen content. In addition, it is considered that the safety is obtained through various factors such as preferential blood distribution to important organs (in particular to the myocardium), more efficient extraction of oxygen from the blood, and the decreased work load resulting from a reduced blood viscosity. PMID- 7861600 TI - [Evaluation of cerebral circulation and cerebrovascular CO2 reactivity with transcranial Doppler ultrasonography]. AB - We examined the cerebrovascular CO2 reactivity (K) determined by measurements of the middle cerebral artery blood flow velocity (Vm) with transcranial Doppler ultrasonography (TCD) in 24 anesthetized patients. The relationship between Vm and mean arterial blood pressure (mBP) showed a linear regression in each constant level of PaCO2. The exponential curve with an exponent of 0.0399 mmHg-1 was found to be the best fit to the plotted data of Vm against PaCO2 during normotension of 90 mmHg. The following equation was used to evaluate K from the two flow values, because the calculated K value would be logically constant, i.e., an exponent of Vm/PaCO2 exponential curve: K (mmHg-1) = delta lnVm/delta PaCO2 = (lnVm(1) - lnVm(2)/(PaCO2(1) - PaCO2(2)). The validity of K values could be enhanced under conditions of the delta PaCO2 > or = 12.5 mmHg and the variation in arranged mBP < or = 30 mmHg. This methodology with TCD can be used to correlate changes in cerebral blood flow and provide much benefit for the evaluation of cerebrovascular CO2 reactivity. PMID- 7861601 TI - [The hemodynamic changes during the intraperitoneal hyperthermic perfusion under induced hypothermia]. AB - We investigated the whole body oxygen consumption (VO2) and the hemodynamic changes during the intraperitoneal hyperthermic perfusion (IPHP), which was coupled with induced hypothermia to prevent the cerebral disorder. IPHP was carried out for 90-120 min with 45-47 degrees C perfusate after the operation. We induced hypothermia using the surface cooling method and the infusion of triflupromazin. In no patient, the pulmonary artery temperature (PAT) rose above 40 degrees C. In the IPHP, there was a significant correlation between VO2 and PAT. If PAT reached 42 degrees C during the IPHP, VO2 would increase to 130-140% of the value at 37-38 degrees C. This rise is smaller than that during the total body hyperthermia (TBH), in which VO2 at 42 degrees C reached 130-190% of the value at 38 degrees C. Heart rate increased in proportion to the rising rate of body temperature. During the IPHP, PAT sometimes rose remarkably about 8 degrees C (from 32 degrees C to 40 degrees C) with a marked rise in heart rate. This rising rate of PAT is greater than that of TBH, in which PAT rose about 4-5 degrees C (from 37-38 degrees C to 42 degrees C). We consider that IPHP is not applicable to the patients with ischemic heart disease. During the rise of PAT, other circulatory parameters related to IPHP, changed in the same direction as those related to TBH. The rate of change of these parameters related to IPHP was smaller than that of the TBH, because during the IPHP the highest PAT was lower than that during TBH. PMID- 7861602 TI - [Hemodynamics during hypervolemic hemodilution (HH) technique]. AB - In order to avoid blood transfusion in patient, we have been carrying out hypervolemic hemodilution (HH) with HES and Ringer's lactate without blood withdrawal. We studied the hemodynamics during hypervolemic hemodilution in adult mongrel dogs. The dogs were divided into two groups; control group (group C) and nitroglycerin group (group N) in which nitroglycerin was administrated at 1 microgram.kg-1.min-1. During HH, CVP, PAP, PCWP increased remarkably, and they were lower in group N than in group C, and CO increased in group N more than in group C. Though by the acute hemodilution Hct decreased to 30%, PaO2/FIO2, pH, and SvO2 remained within normal ranges. We conclude that HH is a very useful technique to avoid blood transfusion. However, during HH the excessive volume loading is associated with significant increase in CVP and PCWP, and the vasodilating therapy is effective to reduce the volume overloading. PMID- 7861603 TI - [The effect of subcutaneous administration of buprenorphine with patient controlled analgesia system for post-operative pain relief]. AB - We conducted a study comparing patients receiving continuous subcutaneous administration of analgesia with self controlled analgesia system (CSAA group) with those receiving continuous epidural infusion (Epi group) for postoperative analgesia after abdominal surgery. Fourteen patients were randomized into two groups: CSAA group (n = 7) received 20 micrograms.h-1 of buprenorphine (Bu) subcutaneously with additional 20 micrograms of Bu using Baxter infusor BB+PCA; Epg group (n = 7) received continuous epidural infusion of 0.4 mg of Bu and 46 ml of 0.25% bupivacaine daily (16.7 micrograms.h-1 of Bu) using Baxter infusor 2 ml.h-1 type. In both groups, patients received supplemental 0.1 mg of Bu subcutaneously as needed. During 48-hour postoperatively, verbal descriptor pain scale, sedative scale, visual analogue scale, supplemental doses of Bu, and side effects were evaluated. There was no significant difference of verbal descriptor pain scale, sedative scale, visual analogue scale, and supplemental doses of Bu between CSAA group and Epi group. Total doses of Bu during the first 12 hours postoperatively (CSAA group: 0.37 +/- 0.08 mg, Epi group: 0.30 +/- 0.08 mg) were significantly more than those during other 12-hour period in both groups (P < 0.05). There was no severe side effect in both groups. We conclude that continuous subcutaneous administration of analgesic was effective for postoperative analgesia, and almost the same analgesic effect was obtained as compared with continuous epidural analgesia. We calculated that the adequate dose of Bu subcutaneously during early postoperative period to be about 30 micrograms.h-1 of Bu. PMID- 7861604 TI - [Comparison of the clinical usefulness of the two types of combined spinal epidural needles]. AB - The clinical usefulness of Combined Spinal-Epidural (CSE) needles, Portex Spinal/Epidural set (P needles) and Hakko Disposable Needles set type H (H needles) was compared on 30 patients undergoing elective orthopedic lower limb surgeries. Although the calibers of the epidural needles were a little different, both needles were introduced quite easily in the epidural space. The spinal needles were inserted successfully to the subarachnoid space in 27 out of 30 cases by the P needles and 23 out of 30 cases by the H needles. The average trial times for successful insertion of the spinal needles were 1.3 and 2.6 by the P needles and the H needles, respectively. this was statistically significant (P < 0.05). Adequate spinal anesthesia was established in 26 patients (87%) and 19 patients (63%) by the P needles and the H needles, respectively. One case of the accidental location of the epidural catheter in the subarachnoid space was observed in each group. As the CSE device, the P needles were more sophisticatedly designed for easier insertion to the subarachnoid space than the H needles. PMID- 7861605 TI - [Significance of phrenic nerve block in the anesthetic management of laparoscopic cholecystectomy]. AB - The significance of phrenic nerve block was studied in the anesthetic management of laparoscopic cholecystectomy. Right phrenic nerve block with 1% mepivacaine 10 ml was performed after the patients were epidurally catheterized and anesthetized with isoflurane and nitrous oxide in oxygen. Intraoperative anesthetic requirement and postoperative shoulder pain incidence in patients with this block were compared with those in patients without block. Addition of the phrenic nerve block to general and epidural anesthesia did not reduce the intraoperative dosage of isoflurane, but it significantly prevented occurrence of postoperative right shoulder pain. It is known that phrenic nerve contains sensory element and that laparoscopic procedures of gall bladder elicit noxious stimuli which cannot be blocked by ordinary epidural anesthesia for abdominal surgery. Also, shoulder pain is said to be phrenic nerve-mediated referred pain. Our study suggests that blockade of these stimuli is effective in preventing postoperative event rather than intraoperative. PMID- 7861606 TI - [Effects of methylprednisolone on functional recovery of stunned myocardium in dogs]. AB - We investigated the effects of methylprednisolone (MP) on the time course of functional recovery of myocardium following 15 min of coronary artery occlusion and 1 h reperfusion (stunned myocardium) in morphine-urethane-alpha-chloralose anesthetized dogs. Myocardial segmental shortening (%SS) in the subendocardium of ischemic areas was measured by sonomicrometry. MP (30 mg.kg-1 iv) was administrated 90 min before the occlusion period. Compared with the control group, %SS in the ischemic region was significantly (P < 0.05) greater in the MP treated group during 15 to 60 min of the reperfusion period. There were no significant differences in other hemodynamic data between the control and MP treated groups. In conclusion, it was shown that MP enhances the functional recovery of stunned myocardium. PMID- 7861607 TI - [Effects of ketamine on somatosympathetic reflex discharges in cats]. AB - Effects of ketamine on somatosympathetic reflex discharges induced from sympathetic trunk with electrical stimulation of superficial peroneal nerve were investigated in 51 cats under anesthesia with urethane and alpha chloralose. These reflex discharges through spinal cord and medulla oblongata consist of two components, A and C reflexes, which are derived from somatic myelinated and unmyelinated afferent fiber respectively. Amplitudes of both A and C reflex potentials were depressed significantly after intravenous injection of ketamine 10 mg.kg-1. The maximum depression was observed 5 min after administration. In decerebrated cats with surgical transection at the midbrain, both A and C reflexes were also depressed after administration of the same dosages, and the maximum level of the depression was more profound than that in brain intact cats. After intrathecal injection of ketamine 1 mg.kg-1 to the lumbar spinal region, a slight depression of C reflex was found, but, dosages of 10 mg.kg-1 significantly depressed both A and C reflexes to the similar levels as those in iv injection to brain intact cats. The maximum depression was observed 30 min after administration. The depressive effects on both reflexes of intravenous ketamine 10 mg.kg-1 were not antagonized by naloxone 0.06 mg.kg-1 in brain intact cats. These results suggest that the suppressive effects of ketamine on somatosympathetic reflexes are caused by direct inhibition of medulla oblongata and spinal cord, whereas supra-midbrain regions may be activated by ketamine, and the effect of ketamine is predominant on medulla oblongata in this situation rather than on the spinal cord. PMID- 7861608 TI - [Anesthetic management and neurological outcomes of patient for open heart surgery with infective endocarditis and neurological complications]. AB - No reports have focused on neurological outcomes after open heart surgery of patients with infective endocarditis (IE) and neurological complications. We evaluated parameters related to anesthetic management and neurological outcomes. The subjects analyzed were 24 patients who had undergone valvular surgeries under hypothermic cardiopulmonary bypass from April 1978 to December 1990. The patients were divided into two groups according to the interval between onset of neurological complication and the time of operation: 1) acute group (within one month before the surgery: n = 11, 9.4 +/- 9 days; means +/- SD) and 2) chronic group (more than one month before the surgery: n = 13, 120 +/- 80 days). After heart surgery, 5 patients in the acute group showed newly developed neurological abnormality including death from hemorrhagic transformation, hemiplegia or aphasia. No patients in the chronic group had newly developed neurological abnormality related to the surgery. In the neurologically deteriorated patients of the acute group, interval from the onset of neurological complication to surgery was 3.5 +/- 4.5 days, whereas that of the remainders of the acute group was significantly longer (14.4 +/- 9.0 days). Intraoperative events and anesthetic management of these patients were also analyzed. However, there were no significant differences in the parameters such as cerebral perfusion pressure, arterial PaCO2, doses of anesthetics and use of vasopressors. Our results suggest that the most important factor which may influence neurological outcome was the interval between the onset of neurological abnormality and the time of operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861609 TI - [Repeated use of Drug Infusion Balloon Catheter for postoperative pain management]. AB - The purpose of this study was to evaluate repeated use of Drug Infusion Balloon catheter (DIBC) experimentally and clinically. 1. Experimental study: The changes in flow rate by repeated use of DIBC (40 ml.12 h-1 type) were measured under room temperature (21 degrees C). 2. Clinical study: Ten patients scheduled for upper abdominal surgery were studied. DIBC (40 ml.12 h-1 type) was filled with midazolam, buprenorphine, and lidocaine. Twelve hours later, the same DIBC was filled with buprenorphine and lidocaine. The mean flow rates were, on first use; 2.91 +/- 0.51, on the second use; 2.88 +/- 0.45, on the third use; 2.75 +/- 0.44, and on the fourth use; 2.69 +/- 0.38 (ml.h-1, mean +/- SD, n = 6, P < 0.05). In the clinical study, pain scores, rates of supplemental analgesic infusion during 0-12 h period were not different from those during 12-24 h period. No complications were observed in this study. Repeated use of DIBC up to four times yielded reproducible results (+/- 8%). Repeated use of DIBC for postoperative pain relief, changing the contents according to the severity of pain, might be a useful and cost saving method. PMID- 7861610 TI - [Anesthetic management of a patient with Freeman-Sheldon syndrome]. AB - The Freeman-Sheldon syndrome is a rare congenital myopathy and dysplasia that results in deformity of the face, hands, and feet. We describe here some problems in general anesthesia from the anesthetic management point of view. An 8-year-old girl with Freeman-Sheldon syndrome underwent surgery under general anesthesia for the correction of lip deformity and microstomia. Patients with this syndrome may present anesthetic problems involving difficulties in endotracheal intubation due to microstomia, micrognathia and neck rigidity, as well as postoperative respiratory complications and problems that relate to myogenetic morphology and myofunctional abnormalities. Preoperatively, we analyzed X-ray cephalograms to evaluate the difficulty of endotracheal intubation. Fiberscopic endotracheal intubation was performed; the time required was 55 minutes. On recovery from anesthesia and after becoming fully responsive, she was extubated in the operating room without any complications. Postoperative recovery was uneventful. Patients with Freeman-Sheldon syndrome should be managed by good preanesthetic preparation, and attention should be paid to postoperative respiratory complications due to the use of muscle relaxants and to securing intravenous access. PMID- 7861611 TI - [Anesthetic management of patients with dilated cardiomyopathy]. AB - Anesthetic management of patients with dilated cardiomyopathy (DCM) was analyzed. From January 1991 to June 1993, we had 7 patients with DCM; 5 patients received general anesthesia and 2 patients received spinal anesthesia. General anesthesia was induced and maintained generally with diazepam and fentanyl. There were two patients who suffered from intraoperative arrhythmia. One patient who received spinal anesthesia suffered from ventricular fibrillation suddenly before the operation and we performed cardiopulmonary resuscitation successfully but the operation was cancelled. One patient who underwent emergency operation for gastric perforation suffered supraventricular tachycardia during the operation, and we were required to use antiarrhythmic agent that was thought to be deleterious to cardiac function. There was no patient who died perioperatively. There was one patient in the group IV of classification of Inoh which predicts the highest risk of dying from cardiac failure. In conclusion, it is important to control arrhythmia during the management of patients with DCM under anesthesia. PMID- 7861612 TI - [General anesthesia for patients with hypertrophic cardiomyopathy]. AB - General anesthesia was given to six surgical patients with hypertrophic cardiomyopathy on eight occasions from 1990 to 1992. Anesthetic courses were uneventful in five patients diagnosed previously as hypertrophic cardiomyopathy. However, a patient without a diagnosis of hypertrophic cardiomyopathy had intractable cardiac arrest. A slight hypotension caused by epidural anesthesia had a devastating effect on the patient. The above experiences stress the importance of early diagnosis and careful observation in perioperative period. PMID- 7861613 TI - [Use of Bullard intubating laryngoscope in emergency room]. AB - A sixty-year-old male patient with caries of the cervical spine suffered from cardio-respiratory arrest outside the hospital. Laryngeal mask was inserted into his pharynx and he was brought to the emergency department of our hospital under CPR by emergency paramedical staffs. Endotracheal intubation was tried three times with a Macintosh laryngoscope but was unsuccessful. His neck was difficult to extend and his epiglottis was not visible at all (X-ray photograph showed the fusion and the significant backward protrusion of his cervical spine). EGTA and Combitube were tried but in vain. At last Bullard intubating laryngoscope with videocamera system was operated. An endotracheal tube was easily inserted into his trachea with it and effective cardiopulmonary resuscitation was managed under reliable airway maintenance. These facts indicate that Bullard intubating laryngoscope is valuable at the emergency department and it should be always available there. PMID- 7861614 TI - [Magnetic resonance imaging (MRI) of bone marrow necrosis]. AB - Magnetic resonance (MR) of bone marrow was studied in two cases of acute leukemia which showed bone marrow necrosis. Case 1:A 24-year-old female was admitted because of sternum pain and bleeding tendency. She was diagnosed AML based on the peripheral blood picture. Bone marrow biopsy revealed the presence of bone marrow necrosis. T1 weighted imaging of MR showed low signal intensity in all vertebral marrow. Fatty marrow was demonstrated after achieving complete remission and the MR imaging of bone marrow changed to show high intensity, suggesting fat deposition. Case 2: A 19-year-old female suffered from chest pain and lumbago, and was diagnosed as ALL. DIC and bone marrow necrosis were confirmed during chemotherapy for remission induction. T1 weighted imaging showed the mosaic pattern of low and high signal intensity. She achieved complete remission and bone marrow clot revealed the presence of fatty marrow. Most areas of low signal intensity of T1 weighted imaging changed to those of high signal intensity. These observations suggest that necrotized bone marrow seemed to change to fatty marrow along with achieving remission. MR imaging study of bone marrow is useful for evaluating hematopoiesis in hematologic disorders. PMID- 7861615 TI - [Atypical chronic myeloproliferative disorder with translocation (12;13) (p13;q12) and tumor formation]. AB - A 49 year-old man was admitted to our hospital in May 1989, with a cervical tumor and leukocytosis. He had been pointed out leukocytosis for last two years. Peripheral blood examinations demonstrated an increase of leukocytes (39,500/microliters) with low neutrophil alkaline phosphatase, eosinophilia and immature cells. Examination of bone marrow revealed normoplasia with 5.6% eosinophils, 1.4% myeloblasts, 2.6% promyelocytes and 250/microliters megakaryocytes. Cytogenetic analysis disclosed 46, XY, t (12;13) (p13;q12). Southern blot analysis showed no BCR rearrangement. The tumor cells had infiltrated the lymph nodes. Pathological finding agreed with the specimen of the lymph node as in the clot section of bone marrow. He was diagnosed as having a chronic myeloproliferative disorder with tumor formation and was treated with anti-leukemia drugs, including BH-AC, THP, VDS, MTX, VP-16, BUS, 6MP and uvenimex. He showed hematological remission, temporary, but he did not reach cytogenetical remission and died in April 1990. Further study in a large series is necessary to define whether the abnormality of the chromosome with t(12;13) (p13;q12) is characteristic in cases with tumor formation. PMID- 7861616 TI - [Multiple myeloma with massive ascites fluid--immunophenotypic analysis of myeloma cell and its IL-6-dependent growth]. AB - A 75-year-old female was diagnosed as having multiple myeloma (IgG.lambda type. Stage IIA) with plasmacytoma of the head and back in October, 1989. She obtained partial remission by MCNU and MP therapy, but relapsed with massive ascites in January, 1991. VAD therapy was not effective and she died of multiple organ failure on February 23. Her ascites contained a large number of myeloma cells, and the phenotypic analysis and the response to interleukin-6 (IL-6) of these myeloma cells were examined. The myeloma cells were positive for CD33, CD45, CD45RA, CD63, CD71, plasma cell associated antigens such as CD38, PCA-1, BL3, and various kinds of adhesion molecules: CD11a/CD18 (LFA-1), CD29 (VLA-beta 1), CD44 (H-CAM), CD49d (VLA-4), CD54 (ICAM-1), CD56 (N-CAM), CD58 (LFA-3). IL-6 level in the ascites was increased at 91.0pg/ml. The myeloma cells showed an IL-6 dependent growth, which was inhibited by anti-IL-6 antibody (Ab) and anti-IL-6 receptor Ab in vitro. Myeloma cells appearing in ascites have rarely been reported. Our case suggested that IL-6 was a potent growth factor of myeloma cells through an autocrine mechanism in the ascites, and resulted in an aggressive myeloma. PMID- 7861617 TI - [A case of Jordans' anomaly]. AB - A 35-years old female with Jordans' anomaly was reported. She had been treated for diabetes mellitus and hypertension at another hospital. She was admitted to our hospital for operation for diabetic retinopathy on July 9, 1992. Wright Giemsa stained peripheral blood smear revealed multiple vacuoles in the cytoplasm of the granulocytes and monocytes. Histochemical studies of these vacuoles showed positive for Sudan III but negative for peroxidase, alkaline phosphatase and PAS staining. Electron microscopic examination revealed that lipid containing vacuoles had no clear membrane and were not associated with cell organelles. Laboratory findings of the serum showed hyperglycemia (FBS 188mg/dl), high HbA1c level (9.4%) and mild type IIa hyperlipidemia. Abdominal sonogram and abdominal CT showed no remarkable abnormalities except for mild fatty liver. Her elder sister and daughter had similar morphological findings in granulocytes, monocytes and lymphocytes. PMID- 7861618 TI - [Anterior segment of the eye and cranial nervous (II, III, VI, VII) infiltration in relapsing acute lymphoblastic leukemia (L1)]. AB - A 42-year-old male was admitted with nasal bleeding. On admission he showed no abnormal neurological sign. A diagnosis of acute lymphoblastic leukemia (ALL) (L1) was made, and modified L-10M protocol was performed. During consolidation chemotherapy, the bone marrow was in remission but he showed left facial palsy. Four days after the onset of left facial palsy, the patient developed bilateral facial palsy followed by left oculomotor and abducens nerve palsy. At this time, bilateral ocular fundus showed papilloedema, exudate, bleeding, Roth's spot and leukemic infiltration to the anterior segment of the eye. Systemic chemotherapy with intrathecal injection of anti-leukemic drugs and whole brain irradiation was partially successful against cranial nervous system (CNS) complaints, but the patient relapsed. Seven month later hypopyon and secondary glaucoma developed and trabeculectomy was performed. The bone marrow revealed an increase of leukemic blasts. Chemotherapy consisting of various drugs was not effective, and he died of pneumonia. In this case, although intrathecal chemotherapy and whole brain irradiation were attempted, leukemia evolved CNS, retina and uvea despite the fact that the bone marrow was in complete remission, allowing various cranial nerve signs and ocular manifestations to occur. PMID- 7861619 TI - [Significance of heat shock protein in gastric lesions--gastric mucosal cells culture]. PMID- 7861620 TI - [A gallbladder carcinoma with metastatic skin lesions as the first diagnostic clue; report of a case]. PMID- 7861621 TI - [A case of pleomorphic carcinoma of the pancreas]. PMID- 7861622 TI - [Establishment and pathological study of a new poorly differentiated mucinous gastric cancer cell line]. AB - We succeeded in establishing a human gastric carcinoma cell line (KE-97) from oncocytes obtained from the mesentery disseminated metastatic focus of a 52-year old male stomach cancer patient. From a histopathological point of view the gastric carcinoma was clearly a mucin-producing mucinous carcinoma, portion of which were mixed with poorly differentiated adenocarcinoma and signet-ring cell carcinoma. The oncocytes were fused into a mass and exhibited a suspended proliferating system, with a doubling time of about 28.8 hours. Transplantation of the cancer cells into skid mice resulted in a tumor system in all cases, and histologically, mucinous vacuoles were found in the cell membranes. With immunological staining they were found to be positive for anti-CEA antibodies, anti-CA19-9 antibodies and anti-ICAM-1 antibodies. Autopsy found extensive hematogenous metastasis (lung, liver) and cancerous peritonitis. KE-97 is mucinous carcinoma, and it was reported with the belief that it is a useful cell line upon the investigation of its cancer metastasis mechanism and cytological characteristics. PMID- 7861623 TI - [Clinical study of ileus like symptom due to eating of raw firefly squid, Watasenia scintillans]. AB - We report 12 patients who ate raw firefly squid, Watasenia scintillans. The patients experienced abdominal pain one or two days after eating them. Ileus was suspected by abdominal X-ray, but abdominal muscle guarding was not recognized. No specific findings was revealed on laboratory data. Patients were recovered two or three days after admission by only drip infusion. Recently, type X larva of the suborder Spirurina is recognized in 3.3% of firefly squid viscus. Indirect fluorescent antibody test using antigen of the type X larva was evaluated for the sera of the 8 ileus patients who were admitted in 1993. The antibody titers were positive in 5 patients and were negative in 3 patients. These results suggested that the ileus like symptom we reported here was attributed to the type X larva of the suborder Spirurina. PMID- 7861624 TI - [Home enteral nutrition for the maintenance of remission in patients with Crohn's disease--including comparison between Elental and Enterued]. AB - Therapeutic efficacy of Elental and Enterued as home enteral nutrition (HEN) for the maintenance of remission in 32 patients with quiescent Crohn's disease was studied retrospectively. Their cumulative rates of continuous remission and non hospitalization were statistically compared in relation to following five factors; type of disease, history of bowel resection, duration of disease, oral bile acid tolerance test (OBATT) and radiological lesion score (RLS). As to the cumulative rates of continuous remission and non hospitalization, there was no significant difference between two groups treated with Elental and Enterued. In patient with ileocolitis type, > or = 5-year history, and a high score of RLS, few cases could continuously maintain remission following a long-term HEN. Especially, patients with low absorption in OBATT had a significantly lower cumulative rate of continuous remission than those with normal absorption in OBATT. The present results suggest that above factors may be useful in the application of HEN to patients with Crohn's disease. PMID- 7861625 TI - [Follow-up study of hepatic hemangiomas]. AB - Hepatic hemangioma is the most common benign tumor of the liver, but there are a few reports on chronological changes in size of hepatic hemangioma. To elucidate natural history of hepatic hemangioma, we evaluated consecutive ultrasonograms of 27 hemangiomas in 23 patients. Underlying liver disease in these 23 patients included seven cases with chronic hepatitis, five cases with liver cirrhosis and three cases with fatty liver. The remaining eight cases showed no evidence of liver disease. Follow-up period ranged 12 to 114 months (average 44). During the follow-up, six (22.2%) hemangiomas changed in size on US, which included three lesions with increase in size, one lesion with decrease in size and two lesions with spontaneous regression. Of 12 patients with chronic liver disease, only one patient showed significant change in the hemangioma size, which regressed spontaneously. These results showed that there was no case showing increase in size of hemangioma in patients with chronic liver disease. Thus, if clinically diagnosed hemangioma which tends to increase in size is detected on US or other imaging modalities in patients with chronic liver disease, aimed aspiration biopsy should be preferably performed considering the possibility of hepatocellular carcinoma. PMID- 7861626 TI - [Clinical evaluation of prophylactic sclerotherapy for esophageal varices in patients with unresectable hepatocellular carcinoma--based on patients treated with transcatheter arterial embolization]. AB - A clinical study on efficacy of prophylactic sclerotherapy for esophageal varices was carried out on 220 patients with unresectable hepatoma treated with TAE. They were classified into 3 groups: 1) Prophylactic group with prophylactic sclerotherapy for RC sign positive varices (45 cases), 2) Non-prophylactic group with RC sign positive varices without prophylactic sclerotherapy (31 cases), 3) RC negative group in which RC sign was negative in whole time (144 cases). Although atypical RC sign or venous dilatation was noticed in 54% of patients in prophylactic group at 1-year after sclerotherapy, cumulative bleeding rates after detection of RC sign positive varices in prophylactic group (27% at 2-years) were significantly lower (p < 0.001) than those in non-prophylactic group (91% at 2 years). The incidence of death by variceal bleeding in prophylactic group (6%) was significantly lower (p < 0.005) than that in non-prophylactic group (36%). 50% survival period of prophylactic group (25.0 months) was significantly longer (p < 0.001) than that of non-prophylactic group (12.5 months), and there was no significant difference of 50% survival period between prophylactic group and RC negative group (21.6 months). We conclude that, prophylactic sclerotherapy not only decrease incidence of variceal bleeding and of death due to bleeding, but also improve survival rate in hepatoma patients with RC sign positive esophageal varices. PMID- 7861627 TI - [Interferon treatment for chronic hepatitis C--assessment of 3 regimens in patients received more than 500MU interferon treatment and their effect predictive factors for interferon treatment using multivariate analysis with the logistic regression model]. AB - Chronic hepatitis C patients (n = 115) were treated with interferon (IFN). Total dose employed was more than 500 MU. The response rate was assessed among the three treatment groups: 2W continuous+TIW, 4W continuous+TIW, 8W continuous+TIW. The IFN treatment effect predictive factors were also assessed. Complete response (CR) rate, CR with serum HCV-RNA disappearance rate, responders' histology activity index score changes between before and after treatment, and responders' hepatocytes HCV-RNA disappearance rate did not differ among the three treatment regimens. CR to IFN treatment was dependent on serum HCV-RNA and HCV serotype. Patients of low serum HCV-RNA and serotype II were responsive to IFN treatment. PMID- 7861628 TI - [Effect of long-term ursodeoxycholic acid treatment on serum liver enzymes and serum bile acid metabolism in chronic hepatitis]. AB - The effect of ursodeoxycholic acid (UDCA) treatment for more than one year on chronic hepatitis in regard to responder and non-responder and influence of UDCA administration on serum bile acid metabolism were studied. All of non-responders (16 patients) were hepatitis B or C patients, and seven of fifteen responders were negative for hepatitis B and C virus marker and could be considered autoimmune hepatitis. These patients got drastic improvement of liver function test, anti-nuclear antibody in five patients and anti-smooth muscle antibody in three patients were decreased. Although HAI scores for liver pathology before UDCA treatment were not different between responders and non-responders, the intralobular necrosis was improved in responders after UDCA treatment. Concerning serum bile acid analysis, total bile acid and UDCA concentration in responders were lower than non-responders. Percentage of iso-ursodeoxycholic acid in responders was significantly higher than non-responders. These results suggest the effectiveness of UDCA therapy on autoimmune hepatitis. PMID- 7861629 TI - [Evaluation of the special therapies in fulminant viral hepatitis--a multi institution study]. AB - Prognostic factors and the efficacy of therapy were studied on 518 patients with fulminant viral hepatitis collected as a joint study from the active members of the Japanese Gastroenterological Society during the period from 1983 to 1988. Using five independent prognostic variables (patients' age, occurrence of infection, gastrointestinal bleeding, renal failure and coexistence of accompanying diseases), a prognosis discriminating logistic model was constructed. A risk score was calculated from the model and patients were classified into two groups with high and low probabilities of survival according to the score. In patients with the duration of illness more than ten days before development of encephalopathy, survival rate of patients given Fischer's amino acid solution was significantly low compared with those not given in the group of low survival probability. A similar deleterious effect of the amino acid solution was proven with another logistic model comprising three more covariates (prothrombin percent, total birirubin level on the day of development of hepatic encephalopathy and the duration of illness before encephalopathy) on 391 patients without missing data on these items. No significant life saving effect was observed on plasma exchange, charcoal hemoperfusion, glucagon-insulin therapy, H2 receptor antagonist and steroid. By Cox's proportional hazard model, plasma exchange was found to double the survival period of patients after development of encephalopathy (p < 0.001). PMID- 7861630 TI - [A case of extragastric leiomyoblastoma with a narrow stalk]. PMID- 7861631 TI - [A case report: successful treatment of intractable fundic variceal hemorrhage by direct catheterization of the mesenteric vein and embolization]. PMID- 7861632 TI - [A case of arteriovenous malformation of the jejunum: the advantage of angio-CT in diagnosis]. PMID- 7861633 TI - [A case of tuberculosis of the ascending colon associated with ileus and fistula formation]. PMID- 7861634 TI - [Exacerbation of hypertriglyceridemia in two patients with chronic hepatitis C during interferon therapy]. PMID- 7861635 TI - [A case of non-cirrhotic portal hypertension complicated with Sjogren syndrome and thrombocytosis]. PMID- 7861636 TI - [Some findings of the lung in medicolegal autopsy cases]. AB - "At first glance the lungs may seem uncomplicated, but many wise men have gone astray in their labyrinths." These words were written by Dr. A.A. Liebow, a famous pathologist, in a foreword to the first edition of Pathology of the Lung by H. Spencer. This same thought can also be applied to the field of medicolegal autopsies. 1. The gross appearance of the lungs in medicolegal autopsies Plucks consisting of the lungs, neck organs, the esophagus and the aorta were removed from human cadavers and after taking photos of the frontal and rear view, the lungs were carefully examined to reveal whether the lung shows characteristic morphological changes depending on causes of death. Based on their appearance, the lungs were classified into the 3 following types: a collapsed, a non collapsed and an inflated type, each of these types reflecting the probable cause of death. The collapsed type of lung was seen in cases of death from exanguination, and the lung falling into shrinkage due to traumatic pneumo- and/or hemo-thorax was also classified into the collapsed type. The non-collapsed type of lung was seen in cases whose lungs were thermo-coagulated and in a case of death from a pulmonary embolism. Also, the deflating lungs of drowning victims before falling into collapse, were classified into a non-collapsed type. The inflated type of lung consisted of lungs that showed ballooning soon after death by drowning, and lungs that had inflated due to emphysema or edema from various causes. This lung study has reconfirmed that the lungs show hypostatic changes more clearly than any other organs of the body, and in the absence of skin color changes reflecting hypostasis, the settling of the blood in the lung could be detected in most cases. 2. Early histopathological lung changes induced by shock One hundred and thirty medicolegal cases were reviewed to detect early histopathological changes of the lung induced by shock. In many cases of death from various causes, pulmonary edema and hemorrhage were noted, but the incidence of such changes did not reveal any significant differences among the causes of death. When death had resulted from a hemorrhage or occurred during a state of shock, megakaryocytes in the pulmonary vessels tended to increase. However, if death from such causes had occurred shortly after the event, no increase in megakaryocytes was noted.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7861637 TI - [Lung surfactant: its application to the lung in asphyxia]. AB - This study is a research of the lung in the hypoxic or anoxic state. The examination of lung were performed by light and electron microscopy with the immunohistochemical methods and biochemical analysis of the lung lavage, not only for the morphological appearance of the surfactant but also the changes of its localization and secretion. For the circumstance of hypoxic or anoxic state, gases of carbon dioxide, methane, carbon monoxide and freon were prepared regulating their contents with a fluorometer. In the first stage of the examination, the lung of a rat inhaled the air containing 5% of oxygen showed the so-called tubular myelin which is a lattice-like structure. And this structure was very much like those found in the alveolar space of a new born rat which is lamellar and lattice-like structure coming loosened to a monolayer. This structure is regarded as the morphological expression of the excreted lung surfactant. The appearance of the tubular myelin was observed in the hypoxic state prepared by the gases stated above. By the examination of the lung lavage of rats inhaled the hypoxic air, the contents of phospholipid and protein were showed 2 and 5 times more than those of control rats, respectively. In the human lung which was collected from the dead body diagnosed the cause of death was asphyxia, the tubular myelin was found by the electron microscopy in some cases of the strangulation of the neck, and the immunohistochemical reaction products were also observed by using the anti-human lung surfactant apoprotein mouse antibody, PE10 of SP-A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861638 TI - [Pathophysiological study of asphyxia and its applications to medico-legal diagnosis]. AB - Asphyxia is commonly defined as "a hypoxic state in the body" which is caused by any one of a wide range of events, starting from an insufficiency of atmospheric oxygen to a failure in oxygen uptake by the cells. The present study outlines a physiopathological study of "mechanical asphyxia" various types of hypoxia caused by mechanical compression of the cervical and thoracic regions and its application to medicolegal diagnosis. We used an animal model in which an actual asphyctic condition was experimentally recreated. By elaborating the asphyctic mechanism through the physiological dynamics of the body fluids and tissues during the fatal process and the succeeding short time span, the study was intended to estimate the causes of death, time lapse after death before the examination, and the time of death in persons who were subjected to investigation, autopsy, or forensic examination. Our intention was also to establish medicolegal indices for the cause of death by examining patients who were resuscitated or expired before arrival (DOA). Our past superimental findings indicate that asphyxia is a state in which arterial blood gas anomalies (hypoxemia and hypercapnia) develop due to a disturbance in the respiratory mechanism, disrupting the maintenance of normal bodily functions by the organism. Among the clinical conditions of respiratory insufficiencies, asphyxia caused by external mechanical, factors (such as external application of pressure to the naso-oral, cervical, or thoracic region, insertion of a foreign body into the airway, and aspiration of fluids) corresponds to acute respiratory insufficiency due to hypercapnia type. In most of these cases with mechanical asphyxia, ventilatory insufficiency due to a lack of O2 in the inhaled air and insufficient removal of CO2 through expiration causes pulmonary alveolar hypoventilation and hyperemia associated with hypercapnia. Consequently, hypoxic hypoxia with systemic disturbances develops. The rapidity of development of the clinical events is correlated with the velocity of the rise in blood CO2 level and the development of acidemia from the early stage. The conditions culminate in non compensatory (acute) respiratory acidosis. These abnormal physiological changes in turn produce symptoms such as congestion and cyanotic petechia. Asphyxia ensues if no resuscitation or other medical treatment is available during this stage (the so-called early asphctic stage). We believe that an understanding of these physiopathologic changes is useful in the diagnoses of asphyxia. It is also useful in the diagnosis of the above-cited process in cases of DOA and in patients who have received resuscitation or other medical treatment. PMID- 7861639 TI - [Progress in the research on DNA polymorphism]. PMID- 7861640 TI - [ABO genotyping of fingerprints by the PCR-RFLP method]. AB - DNA typing of the ABO blood groups from single fingerprints was examined. Genomic DNAs were extracted from fingerprints on slide glasses by a simple method with NaI and N-lauroyl-sarcocinate, and then subjected to the PCR (Polymerase chain reaction). Two PCR fragments spanning positions 258 and 700 of the cDNA sequence of the ABO locus were amplified. Then, the PCR products were digested with a restriction enzyme, Kpn-1 or Msp-1, for each site. The digested PCR products were analyzed by electrophoresis on polyacrylamide gels for RFLP (Restriction-fragment length polymorphism). Bands on the gel were visualized by silver staining. Genotyping from single fingerprints after treatment with aluminium powder was also possible by these techniques. PMID- 7861641 TI - Discrimination between postmortem and antemortem blood by a dot-ELISA for human myoglobin. AB - A method for discriminating between postmortem and antemortem blood from bloodstains by detection of human myoglobin using a dot-ELISA was devised, and its applicability to forensic practice was investigated. This method exploits the high amount of myoglobin present in postmortem blood in comparison with that in antemortem blood. Our dot-ELISA was able to detect human myoglobin from bloodstains containing more than 10 micrograms/ml myoglobin, the level commonly observed in postmortem blood. Using this method, 10 stains of postmortem blood and 10 of antemortem blood were all identified correctly. A one-year-old stain made of postmortem blood and a stain of bloody fluid obtained from a severely putrefied body 4 months after death were identified as postmortem blood by this method. Two practical cases for which this method was applied are presented. PMID- 7861642 TI - [A review of recent studies investigating the relationship between sudden infant death syndrome and sleeping position]. AB - Recent references (articles and letters) investigating relationship between sudden infant death syndrome (SIDS) and sleeping position are presented. There are many articles which have reported about this association, although repeated investigation or letters by the same researchers were contained. More than 10 epidemiological data in different area or countries were published. The vast majority of reports are retrospective case-control studies, and no study has found prone sleeping to be more common in control cases than in SIDS, although this relation has not always been statistically significant. In addition, a few intervention studies and one cohort study also showed prone sleeping position was associated with an increased risk of SIDS. The recent autopsy cases from Tokyo Medical Examiner's Office showed that most of SIDS infant whose position was recorded were found prone position, and the result was not conflict with reports from Europe and Oceania. Judging from the result of all epidemiological studies, I agree a link between the increased risk of SIDS and prone sleeping position. Health authorities in five developed countries (Netherlands, New Zealand, Australia, the UK and the USA) have advised parents not to place their infant prone to sleep. In these countries except the USA, the reduction of the incidence of SIDS has been reported. In the USA, the prone sleeping has been traditionally received and the incidence of SIDS is lower than in reports from other countries, so all SIDS researchers do not admit the risk of prone sleeping position. The reason of the association between SIDS and prone sleeping position is unknown, but some researchers have thought the mechanism is likelihood of suffocation by rebreathing or/and airway obstruction on particular type of cot, mattress, bedding or clothes. The medical examination system in Japan covers only four regions (the 23 wards in Tokyo, Yokohama, Osaka, Kobe). In almost all other regions, it is difficult to perform the reliable epidemiological study. However, we should collect more Japanese data, as far as possible, before we determine and recommend the "safer" sleeping position of Japanese infants. We need to get further information about not only sleeping position but also other infant care practices. PMID- 7861643 TI - [An autopsy case of Sjogren syndrome with organized and fresh subdural hemorrhage (hematoma)]. AB - An autopsy case of Sjogren syndrome with organized and fresh subdural hemorrhages (hematoma) is reported. A 49-year-old woman who had been suffering from Sjogren syndrome had gradually lost her consciousness and was taken to the hospital where she died several hours later. Subsequently a doctor found the subdural hematoma of unknown origin on her Brain CT. At autopsy, her skin was dry and all of her teeth were missing. There were sporadic cutaneous purpura and subcutaneous hemorrhages in her trunk and limbs. The histopathological examination revealed that the submandibular gland had no normal acini, and was replaced by fibrous and adipose tissues with numerous lymphocytes. There were signs of fibrosis with inflammation in her liver, kidneys and lungs. The thyroid gland showed thyroiditis. Serological findings showed a significant high level of antinuclear antibody, positive RA factor and high gamma-globulinemia. The autopsy revealed that her cause of death was acute subdural hematoma and uncal herniation. There were no external injuries on her head or face. It is suggested that her acute subdural hematoma according to the hemorrhagic tendency, affected by her Sjogren syndrome. PMID- 7861644 TI - [Low serum TSH levels in patients with emergent conditions due to ischemic heart disease or congestive heart failure]. AB - We investigated the pathophysiological and clinical significance of thyroid stimulating hormone (TSH) levels in patients within 4 days after onset of ischemic heart disease (IHD) or aggravation of congestive heart failure (CHF) due to myocardial infarction. We classified patients into 3 groups: 1) angina pectoris (AP) group [n = 66, 62 years (Mean)], 2) acute myocardial infarction (AMI) group (n = 58, 65 years) and 3) CHF group (n = 16, 68 years). Soon after admission, blood samples were obtained to measure TSH by the IRMA method. Blood samples for creatine phosphokinase (CPK) were obtained every 3 hours. All patients showed TSH levels that were normal or below normal. Those in whom TSH levels were below normal, were defined as "low TSH" patients. The incidence of low TSH patients in the CHF group (31.3%) was significantly higher (p < 0.05) than that in the AP group (4.5%). In the AMI group, plasma CPK activity of 5037 +/- 1102 U/l (Mean +/- SEM) in low TSH patients were significantly higher (p < 0.05) than that of 1931 +/- 255 U/l in patients with normal TSH levels. These results indicate that in patients with extensive myocardial cell damage, "low TSH" frequently develops during emergency. PMID- 7861645 TI - [Assessment of myocardial contraction and relaxation with 99mTc-tetrofosmin multi gated myocardial SPECT]. AB - Myocardial relaxation at the diastolic phase was not evaluated by multi-gated myocardial SPECT, although myocardial contraction at the systolic phase was studied by percent wall thickening and Bull's eye methods. We make out a myocardial volume curve and report to evaluate the myocardial relaxation using multi-gated myocardial SPECT. The study population consisted of 3 normal human subjects (3 male, 32-37 years old), 10 idiopathic cardiomyopathy, 10 coronary artery disease and 1 hypertensive heart disease combined with aortic regurgitation. All cases were injected 555 MBq of 99mTc-tetrofosmin (Amersham Healthcare Corporation) intravenously at rest. A triple detector gamma-camera (GCA-9300A, Toshiba Medical, Japan) and a data processing computer (GMS-5500A, Toshiba Medical, Japan) were used in this study. A cardiac cycle (R-R interval) was divided by 16 frames (50-80 msec per 1 frame). Eight myocardial volume curves were calculated at the anterior wall, apex and inferior wall of the vertical long axis view and were calculated at the septal wall, apex and lateral wall of the horizontal long axis view, respectively. The patterns of the myocardial volume curves were classified into 5 patterns (Normal pattern (N), Delayed Contraction pattern (DC), Delayed Relaxation pattern (DR), Mixed pattern (M) and Normal pattern with Decreased amplitude (ND)). Myocardial uptake was evaluated visually of grading into severe hypertrophy (5), hypertrophy (4), normal (3), mild hypoperfusion (2), hypoperfusion (1) and perfusion defect (0). We compared patterns of the myocardial volume curves to myocardial uptake in the same segments. It was possible to detect myocardial edge of the total 16 frames with 50-60% threshold in the normal volunteer and in patients with hypertrophic cardiomyopathy and to make a myocardial volume curve. The region of the severe myocardial perfusion defect could be detected with 20% threshold in patients with old myocardial infarction. In comparison with myocardial volume curves and myocardial uptake, 74.6% in the N pattern had a normal uptake (3), 66.7% in the ND pattern had a normal uptake (3), 61.5% in the DC pattern had a hypoperfusion segment (0, 1 or fill-in to normal uptake), 44.4% in the DR pattern had a hypertrophic segment (4, 5 or fill-in to increased uptake). The pattern of myocardial volume curve indicates myocardial contractility and relaxation in each myocardial segment. PMID- 7861646 TI - [Is myocardial fatty acid metabolism different between hypertrophic cardiomyopathy and hypertensive hypertrophy?]. AB - To investigate the characteristics of fatty acid metabolism in hypertrophic cardiomyopathy (HCM), we performed myocardial imaging with 123I-iodophenyl-3 methylpentadecanoic acid (BMIPP) in 24 patients with HCM, 13 patients with hypertensive hypertrophy (HT) and 10 normal subjects. Rest myocardial imaging with 123I-BMIPP was obtained at 20 minutes and 3 hours after 123I-BMIPP injection. Rest 201Tl imaging was also performed. In addition to ordinary tomography, whole body imaging was performed to calculate % Uptake (percentage of cardiac uptake of the isotope to total injected dose). As global indexes of fatty acid metabolism, we calculated two parameters; 1) Uptake Ratio (%Uptake of 123I BMIPP normalized by myocardial perfusion) and 2) WOR (percent reduction of myocardial 123I-BMIPP within 3 hours). Regional abnormality was evaluated by visual assessment of ordinary tomograms and by BMIPP/T1 map. BMIPP/T1 map was made from Bull's-eye maps of 123I-BMIPP and 201Tl, and it represented 123I-BMIPP uptake normalized by myocardial perfusion of each pixel which constructed the image. %Uptake of 123I-BMIPP was not different among three groups. But Uptake Ratio was significantly (p < 0.001) different among three groups; normal (1.13 +/ 0.08) > HT (1.03 +/- 0.08) > HCM (0.87 +/- 0.09). WOR of 123I-BMIPP was accelerated in HCM (12.7 +/- 4.7%) and HT (10.2 +/- 2.9%) comparing with that in normal (5.1 +/- 3.1%) (p < 0.01). In patients with HCM, by visual assessment, regional abnormality of 123I-BMIPP distribution was found in 17 of 24 patients (71%) including 3 patients with equivocal abnormality. But in patients with HT, only equivocal abnormality was observed in 23%. In BMIPP/T1 map, abnormality was observed in 92% of HCM and 8% of HT. Although global myocardial fatty acid metabolism was equally disturbed both in HCM and HT, regional abnormality of fatty acid metabolism was observed preferentially in HCM. This indicated myocardial fatty acid metabolism was not identical between HCM and HT. PMID- 7861647 TI - [201Tl scintigraphic evaluation of tumor mass and viability of bone and soft tissue tumors]. AB - To characterize 201Tl uptake in patients with bone and soft-tissue tumor, we studied 49 patients with surgically proven tumors and one patient with a tumor diagnosed arteriographically. In 37 of our 50 patients, the tumor was evaluated with 201Tl and arteriography. Moreover, in 14 of patients with pre-operative chemotherapy, pathologic changes were graded on the basis of percent tumor necrosis as defined histologically. The percent tumor necrosis histologically was compared with changes in the scintigraphic and conventional angiographic studies. Radiologic comparisons demonstrated a high degree of correlation with images of 201Tl and both arterial and blood pool phase of 99mTc-HMDP. Ninety-six percent of 28 malignant tumors had positive 201Tl uptake. None of the patients showed any thallium accumulation in the soft tissues or skeleton adjacent to the lesion. Activity of 201Tl was mainly dependent upon a tumor blood flow and a vascular density. In of 14 cases with the preoperative chemotherapeutic treatment, 201Tl scintigraphic changes showed concordance with % tumor necrosis. Thallium-201 was superior to 99mTc-HMDP in predicting tumor response to chemotherapy. Interestingly, delayed images of 99mTc-HMDP of 5 responders with > 90% tumor necrosis showed decreased uptake in the adjacent bone to the tumor mass lesions. It seems to be quite all right to consider that a major determinant of 201Tl uptake is intratumoral angiogenecity, which is closely connected with tumor viability. Therefore, 201Tl is a sensitive radiopharmaceutical for detection of vascular rich bone and soft-tissue tumors, and appears to be a simple and an accurate test for evaluating the response to specific therapeutic regimens of malignant bone and soft-tissue tumors. PMID- 7861648 TI - [Therapeutic effectiveness of 131I-MIBG on malignant pheochromocytoma--results of long-term follow-up]. AB - The therapeutic response of 131I-MIBG was evaluated in 4 patients with malignant pheochromocytoma who had been treated with 131I-MIBG and followed-up over 5 years. The patients were 2 men and 2 women with ages ranging from 41 to 69 years old (mean 53 years). The primary tumors in 3 of 4 patients had been resected four to eight years before 131I-MIBG treatment. One patient was diagnosed as adrenal pheochromocytoma, and two were retroperitoneal paraganglioma. And in one patient, the resection of primary mediastinal tumor was not performed due to the adhesion to pericardium but the diagnosis of paraganglioma was obtained by biopsy of bone lesion. All patients showed the clear accumulation of 131I-MIBG in tumor on scintigraphy. The number of doses of 131I-MIBG ranged from one to three times with 3.7 GBq per administration and a cumulative activity from 3.7 to 11.1 GBq. Treatment effect was obvious in one patient with lung, bone, and lymph node metastases whose cumulated absorbed dose with 11.1 GBq of 131I-MIBG exceeded over 150 Gy. At the present time, the duration of survival since the beginning of initial 131I-MIBG therapy is over 5 yrs. The other three patients, however, showed little effects, and died with the disease in 2.6 to 4.1 years after the initial 131I-MIBG therapy. 131I-MIBG will become a promising agent for therapy in patients with malignant pheochromocytoma with high degree of accumulation. PMID- 7861649 TI - [Carbon-11 labeled diacylglycerol for signal transduction imaging: effect of the solubilizer on the distribution and radiation dosimetry]. AB - Carbon-11 labeled diacylglycerol (11C-DAG) has been developed as a signal transduction imaging agent for the CNS, and it can visualize the second messenger. For clinical application by positron CT (PET), the 11C-DAG solution must be prepared for intravenous injection. However, the 11C-DAG does not dissolve in water because of its lipophilicity and requires a solubilizer such as human serum albumin (HSA) and Tween 80 (TW-80). We examined the influence of these solubilizers on the tissue distribution of 11C-DAG, and estimated the radiation dosimetry. In the brain, uptake of 11C-DAG dissolved with HSA was 1.3 1.8 times higher than that of dissolved with TW-80. On the other hand, the lung and spleen showed a higher uptake of 11C-DAG using TW-80 than when using HSA. Especially, the lungs showed 20-40 times higher uptake than when using HSA. Also, the washout of radioactivity from tissue was slower, and the dose of radiation exposure was estimated to be higher, with TW-80 than with HSA. Therefore, between TW-80 and HSA with different solubilizing mechanisms, the later was suggested to be a better solubilizer of 11C-DAG. PMID- 7861650 TI - [The partial volume effect correction for pulmonary mass lesions using a 68Ga/68Ge transmission scan in PET study]. AB - We tried to correct the partial volume effect for pulmonary mass lesions using a 68Ga/68Ge transmission scan. Initially, a fundamental study was done using spherical phantoms and good results were obtained. Next, a clinical evaluation was performed on 28 pulmonary mass lesions ranging in diameter from 0.8 cm to 8.0 cm. The tissue fractions of the mass lesions were obtained by a 68Ga/68Ge transmission scan, where the tissue fraction in the back muscles was assumed to have a value of 1. The tissue fraction of the surrounding lung field was subtracted from that of each mass lesions, and the net tissue fraction was thereby obtained. When no correction was required, the tumor/muscle count ratio (TMR) became higher in proportion with an increase in the mass size. After performing a correction, however, no correlation was observed between them. This method was both easy to perform and reliable, and it is thus considered to be useful for overcoming the partial volume effect in pulmonary mass lesions, although an underestimation may still occur in cases with mass lesions either near the great vessels or the chest wall. PMID- 7861651 TI - [Evaluation of myocardial uptake of beta-methyl-(123I)-iodophenylpentadecanoic acid (123I-BMIPP)]. AB - To evaluate the myocardial uptake of beta-methyl-(123I)-iodophenylpentadecanoic acid (123I-BMIPP), nineteen patients with ischemic heart disease including left ventricular hypertrophy (mean age 63 +/- 7.8, 14 males and 5 females) underwent BMIPP myocardial scintigraphy. Myocardial uptake (MU) of BMIPP to the total injected dose was calculated from anterior view of the planar image in all subjects, and was compared with plasma glucose (BS), triglyceride (TG), and free fatty acid (FFA). It was also compared with left ventricular mass (LVM) calculated with echocardiography. MU was not related to BS, TG, and FFA, however had the positive correlation with LVM (r = 0.676, p < 0.01). Myocardial uptake per left ventricular mass (MU/LVM) had the negative correlation with LVM (r = 0.671, p < 0.01). Further studies for the significance of MU/LVM will be required. PMID- 7861652 TI - [A new one-step, labeled-antibody assay for measuring free thyroid hormone concentrations]. AB - We describe one-step labeled-antibody assays for measuring free T4 and free T3 concentrations in serum, based on a novel principle (Amerlex-MAB). Free T4 or free T3 in the sample competes with a molar excess of a cross-reactant (T3 or T2, respectively), chemically coupled to magnetizable polymer particles, for binding to 125I-labeled monoclonal anti-T4 or anti-T3 antibody, respectively. 125I radioactivity bound to the solid phase is inversely proportional to the serum free T4 or free T3 concentration. This one-step assay apparently proceeds to equilibrium after 30 min at 37 degrees C. Within- and between-assay precision (CV) was < 5.7% for free T4 or 6.2% for free T3. The reference range was between 0.98 and 1.77 ng/100 ml for free T4 and between 2.8 and 4.6 pg/ml for free T3. The measurement of free T4 and free T3 concentrations could clearly discriminate hyperthyroid and hypothyroid patients from euthyroid subjects. These values correlated closely to those obtained by an analog radioimmunoassay (Amerlex-M). This method is free from interference by major T4-binding proteins in serum, showing improved performance, compared to the analog radioimmunoassay, with sera from NTI patients with low serum albumin concentrations or anti-thyroid hormone antibodies. We expect these assays to be clinically useful for the evaluation of thyroid functions. PMID- 7861653 TI - [Simple method to estimate cardiac output using first-pass data on RI angiography]. AB - In order to estimate cardiac output (CO) without using data equilibrium state, a simple index (cardiac output index, COI) was developed from the first-pass data as a ratio of the integrated radioactivity on the right ventricle to the total injected radioactivity. COI was well correlated with CO calculated by the conventional Stewart-Hamilton method (r = 0.894, p < 0.01), and thus, CO could be readily estimated from COI. This index might be useful to estimate CO since it can be obtained even with the agents which distribute to organs. PMID- 7861654 TI - [A useful method to evaluate 11C-methionine uptake using positron emission tomography: determination of the optimal scanning time for evaluation and a comparison between the tumor-to-muscle ratio and the distribution absorption ratio]. AB - We determined the optimal scanning time for evaluating 11C-methionine uptake and then compared the usefulness of the tumor-to-muscle ratio (TMR) with the distribution absorption ratio (DAR) using positron emission tomography. Forty-two PET studies were performed to examine 42 tumorous lesions, 25 normal lung tissues, 23 normal bone marrow and 39 blood pool. In the 42 lesions examined, the TMR at 5, 10-20, 20-32 and 32-40 minutes after 11C-methionine injection, compared with that at 45-60 minutes, was 96 +/- 23%, 91 +/- 8.6%, 94 +/- 6.9% and 96 +/- 6.9%, respectively. A correlation study between the TMR and the DAR demonstrated good results in both the normal tissue (r = 0.96) and the tumorous lesions (r = 0.93). In conclusion, the 11C-methionine uptake can be evaluated at any time from 10 minutes after the injection of 11C-methionine and both the TMR and the DAR are considered to be useful methods for evaluating 11C-methionine uptake using positron emission tomography. PMID- 7861655 TI - Preventive effect of betamipron on nephrotoxicity and uptake of carbapenems in rabbit renal cortex. AB - The preventive effect of betamipron (N-benzoyl-3-propionic acid: BP) on the renal uptake and nephrotoxicity of carbapenems (panipenem and imipenem) was studied in rabbits. Panipenem, a new carbapenem antibiotic, induced nephrotoxicity at a dose of 200 mg/kg, i.v., but this was less severe than that caused by a single dose of imipenem or cephaloridine. Along with the significant reduction of nephrotoxicity, the uptake of these carbapenems in the renal cortex was remarkably inhibited by simultaneous treatment with BP (200 mg/kg, i.v.). These results suggest that BP reduces the nephrotoxicity of carbapenems through inhibiting the active transport of carbapenems in the renal cortex. Because of the low toxicity of BP (LD50 in the rat, more than 3,000 mg/kg, i.v.), it was concluded that BP might be a good candidate for reducing the nephrotoxicity induced by panipenem or imipenem. PMID- 7861656 TI - Effect of anterior unilateral vagotomy on healing of kissing gastric ulcers induced in rats. AB - Unilateral vagotomy causes atrophy of the denervated fundic mucosa in rat stomachs. We examined whether or not unilateral vagotomy delays healing of gastric ulcers induced on the denervated mucosa. Kissing ulcers were induced in the fundus of rat stomachs by intraluminal application of an acetic acid solution. Anterior unilateral vagotomy was performed subdiaphragmatically at the time of ulceration. The healing of gastric ulcers induced on the denervated side was significantly enhanced, whereas that on the vagally intact side was not affected. In unilaterally denervated animals, the total gastric acid secretion (both basal and 2-deoxy-D-glucose stimulated) was inhibited, and the pH around the ulcers was increased only in the anterior side. Repeatedly administered histamine failed to affect the enhanced ulcer healing in unilaterally denervated animals. Gastric emptying and mucosal cell proliferation stimulated by food or pentagastrin were unaffected. Serum gastrin significantly increased 19 days after vagotomy. Gastric relaxation on refeeding was inhibited on the denervated side, but this inhibition of relaxation was reversed by hexamethonium treatment. A liquid diet significantly enhanced the healing of ulcers on both the denervated and vagally intact sides. The mechanism by which unilateral vagotomy accelerates the healing of ulcers on the denervated side appears to relate to the inhibition of both gastric acid secretion and gastric relaxation. PMID- 7861657 TI - Activation of microsomal glutathione S-transferase in tert-butyl hydroperoxide induced oxidative stress of isolated rat liver. AB - The activation of microsomal glutathione S-transferase in oxidative stress was investigated by perfusing isolated rat liver with 1 mM tert-butyl hydroperoxide (t-BuOOH). When the isolated liver was perfused with t-BuOOH for 7 min and 10 min, microsomal, but not cytosolic, glutathione S-transferase activity was increased 1.3-fold and 1.7-fold, respectively, with a concomitant decrease in glutathione content. A dimer protein of microsomal glutathione S-transferase was also detected in the t-BuOOH-perfused liver. The increased microsomal glutathione S-transferase activity after perfusion with t-BuOOH was reversed by dithiothreitol, and the dimer protein of the transferase was also abolished. When the rats were pretreated with the antioxidant alpha-tocopherol or the iron chelator deferoxamine, the increases in microsomal glutathione S-transferase activity and lipid peroxidation caused by t-BuOOH perfusion of the isolated liver was prevented. Furthermore, the activation of microsomal GSH S-transferase by t BuOOH in vitro was also inhibited by incubation of microsomes with alpha tocopherol or deferoxamine. Thus it was confirmed that liver microsomal glutathione S-transferase is activated in the oxidative stress caused by t-BuOOH via thiol oxidation of the enzyme. PMID- 7861658 TI - Blockade of delta-opioid receptors prevents morphine-induced place preference in mice. AB - Effects of highly selective delta-opioid receptor antagonists on the morphine induced place preference in ddY and mu 1-opioid receptor deficient CXBK mice were investigated. Pretreatment with naltrindole (NTI: a non-selective delta-opioid receptor antagonist), 7-benzylidenenaltrexone (BNTX: a selective delta 1-opioid receptor antagonist) or naltriben (NTB: a selective delta 2-opioid receptor antagonist) abolished the morphine-induced place preference in ddY mice in a dose dependent manner. These findings suggest that the morphine-induced place preference may be mediated by both delta 1- and delta 2-opioid receptors. On the other hand, in mu 1-opioid receptor deficient CXBK mice, pretreatment with these selective delta-opioid receptor antagonists did not affect the morphine-induced place preference, although pretreatment with beta-funaltrexamine (beta-FNA: a selective mu-opioid receptor antagonist) significantly inhibited the morphine induced place preference. [D-Pen2,D-Pen5]enkephalin (DPDPE: a delta 1-opioid receptor agonist) and [D-Ala2,Glu4]deltorphin (deltorphin II: a delta 2-opioid receptor agonist) induced a significant place preference in ddY mice, but not in CXBK mice. These results suggest that delta 1- and delta 2-opioid receptors in the nucleus accumbens that are related to the DPDPE- and deltorphin II-induced place preference may be dysfunctional and/or poor in CXBK mice. These findings also indicate that delta 1- and delta 2-opioid receptors may be involved in the modulation of the reinforcing effect of morphine. PMID- 7861659 TI - Pharmacological profile of gastric mucosal protection by marmin and nobiletin from a traditional herbal medicine, Aurantii fructus immaturus. AB - We studied the effects of marmin and nobiletin on the experimental acute gastric lesions, gastric transmucosal potential difference (PD) and gastric motor activity in rats and the contractions of isolated guinea pig ileum. Oral administration of marmin and nobiletin inhibited both the appearance of ethanol induced gastric hemorrhagic lesions dose-dependently in a dose range of 10-50 mg/kg, with ED50 values for marmin and nobiletin being 17.2 and 8.0 mg/kg, respectively. However, marmin and nobiletin had minimal effects on aspirin induced gastric lesions at a dose of 50 mg/kg, respectively. Marmin and nobiletin had no significant influence on the basal PD. Intragastrical administration of marmin and nobiletin at a dose of 25 mg/kg significantly prevented the PD reduction induced by ethanol. Both marmin and nobiletin given intragastrically at 25 mg/kg significantly inhibited gastric motor activity measured as intraluminal pressure recordings. Marmin and nobiletin exhibited concentration-dependent relaxations of contractions induced by acetylcholine, transmural electrical stimulation and histamine in isolated guinea pig ileum, respectively. These findings suggest that the anti-ulcer effects of marmin and nobiletin are ascribed primarily to the maintenance of the mucosal barrier integrity and inhibition of gastric motor activity and secondarily due to the prevention of the effects of endogenous acetylcholine and histamine. PMID- 7861660 TI - Changes in monoamine oxidase activity in rat liver during stress. AB - Effects of some stresses on monoamine oxidase (MAO) activity in rat liver were investigated. Cold stress decreased MAO-A activity. Immobilization stress (IMMO) significantly decreased both MAO-A and MAO-B activities. The MAO-A/MAO-B ratio of the cold stress was significantly decreased, but IMMO was not significantly decreased. These results suggest that cold stress, but not IMMO may change the proportions of the multiple forms of MAO activity. PMID- 7861661 TI - Attenuation of clonidine-induced vascular alpha 1-antagonistic action in hypercholesterolemic rabbit common carotid arteries. AB - We examined the effect of hypercholesterolemia on vasodilatory responses to clonidine in isolated and perfused rabbit common carotid arteries that had been preconstricted by phenylephrine. The responses decreased in rabbits fed an atherogenic diet for 4 or 8 weeks, whereas the responses to acetylcholine, nitroglycerin and substance P were not changed after the cholesterol feeding. Attenuated responses to clonidine were maintained for 24 weeks after cessation of the atherogenic diet, suggesting that this response might be an early marker of atherosclerosis. PMID- 7861662 TI - 2-Methyl-5-HT-induced vasoconstrictions mediated via alpha 1-adrenoceptors in rabbit common carotid arteries. AB - We investigated the effects of 2-methyl-5-HT and 1-phenylbiguanide on isolated and perfused rabbit common carotid arteries by a cannula insertion method. 1 Phenylbiguanide produced neither vasoconstriction nor dilation. On the other hand, 2-methyl-5-HT produced only a vasoconstriction, and the dose-response curve was shifted to the right in parallel by treatment with either ketanserin or bunazosin, although methysergide and granisetron had no antagonistic effect. Moreover, the vasoconstriction was not inhibited by guanethidine and imipramine. These data showed that 2-methyl-5-HT acts as an alpha 1-adrenoceptor agonist but not as a 5-HT3-receptor agonist in this vessel. PMID- 7861663 TI - Involvement of blood glucose in the dimethylthiourea-induced protection against alloxan-induced diabetes. AB - Dimethylthiourea (DMTU, 4.0 mmol/kg) injected into mice 30 min prior to alloxan injection markedly protected mice against the diabetogenic actions of 75 mg/kg alloxan. At 30 min after the above dose of DMTU alone (no alloxan), there was a marked rise in blood glucose. Mannoheptulose, an antagonist of glucose action at pancreatic beta-cells, when given 24 min after DMTU and 6 min before alloxan, eliminated the DMTU-induced protection. The protection was also removed in the fasted mice in which DMTU did not cause hyperglycemia. These results indicate that DMTU protected mice from alloxan-induced diabetes by the indirect mechanism of producing hyperglycemia at the time of alloxan injection. PMID- 7861664 TI - Changes in self-stimulation response during chronic morphine treatment and after withdrawal of morphine in rats. AB - Morphine (5-20 mg/kg, s.c.) dose-dependently inhibited the hypothalamic self stimulation response 1-2 hr after administration of the drug. Thereafter, slight increase in the self-stimulation response was seen 4-8 hr after drug administration. The depressant effect induced by 10 mg/kg, s.c. of morphine on the self-stimulation response was antagonized by 1 mg/kg, s.c. of levallorphan. Repeated administration of morphine (10 mg/kg, s.c.) resulted in an increase of the self-stimulation response. The self-stimulation response rate was increased significantly 24 and 48 hr after withdrawal of morphine in chronic-morphine treated rats; In these rats, the initial dose of morphine (10 mg/kg, injected s.c. twice daily 7 days a week) was increased gradually until at the end of 5 weeks, each dose was 50 mg/kg, s.c. PMID- 7861665 TI - Alendronate modulates osteogenesis of human osteoblastic cells in vitro. AB - The bisphosphonates, which are carbon-substituted pyrophosphates, have been studied extensively both in vivo and in vitro to elucidate their effects on bone tissues and cells. However, because these agents were shown to have a potent inhibitory effect on bone resorption, the majority of studies have focused on only this aspect of bone metabolism. There appears to be less information regarding the direct effect of bisphosphonates on bone formation, so thus we undertook experiments to investigate the effects of bisphosphonates, especially alendronate, on the mineralization and matrix protein synthesis of human osteoblastic cells in vitro. The data show that the bisphosphonates, alendronate, etidronate and pamidronate, suppressed 1,25-dihydroxycholecalciferol (1,25(OH)2D3)-stimulated mineralization of human osteoblastic cells at high concentrations, while relatively lower concentrations of alendronate and etidronate potentiated mineralization of the cells in the presence of 1,25(OH)2D3. The potentiation of mineralization with alendronate was accompanied by increased synthesis of bone matrix proteins, osteocalcin and collagen, and the mRNA of pro alpha(I) collagen. These findings show that in addition to their well known effects on bone resorption, bisphosphonates have significant and direct effects on osteogenesis in osteoblasts in vitro. The actual mechanism remains to be further investigated. PMID- 7861666 TI - Evaluation of the long-lasting antihypertensive action of 7-O-ethylfangchinoline. AB - The antihypertensive effect of 7-O-ethylfangchinoline (TJN-220) was analyzed in an experimental model of hypertensive rats under the conscious condition. Single oral administration of TJN-220 (25 and 50 mg/kg) produced a progressive and long lasting fall of mean blood pressure in spontaneously hypertensive rats (SHRs), deoxycorticosterone acetate (DOCA)-salt hypertensive rats and renal hypertensive rats until 72 hr after the drug administration, but affected neither the heart rate in these hypertensive rats nor the hemodynamic parameters in normotensive rats. In SHRs implanted with a telemetry transmitter, TJN-220 (50 mg/kg, p.o.) produced falls of systolic and diastolic blood pressures and diminished the difference in blood pressure between the dark period and the light period for 3 days, particularly by suppressing the increasing phase of blood pressure during the dark period without influencing heart rate or locomotor activity. On the other hand, nicardipine (10 mg/kg, p.o.) produced a transient fall of blood pressure associated with a tachycardia during the light period on the first day alone. Clonidine (0.3 mg/kg, p.o.) diminished the increasing phases of blood pressure and heart rate during the dark period on the first day alone. Thus, the antihypertensive action of TJN-220 was much longer than those of nicardipine and clonidine. The present results suggest that TJN-220 may have potential for use as a beneficial antihypertensive drug. PMID- 7861667 TI - Effects of Kamikihito, a traditional Chinese medicine, on neurotransmitter receptor binding in the aged rat brain determined by in vitro autoradiography (2): changes in GABAA and benzodiazepine receptor binding. AB - We investigated the effects of the long-term administration of Kamikihito (KKT) on the specific binding of [3H]muscimol and [3H]flunitrazepam in the brains of young and aged rats using in vitro quantitative autoradiography. Specific [3H]muscimol binding in aged rats was decreased in all brain regions examined compared with that in young rats, whereas [3H]flunitrazepam binding did not change in any of the brain regions. Scatchard analysis revealed that the maximal number of [3H]muscimol binding sites in the cortex and thalamus was significantly decreased in aged rats compared with young rats, while its affinity remained unchanged. Long-term administration of KKT in young rats had no effect on either [3H]muscimol or [3H]flunitrazepam binding. In contrast, the same treatment in aged rats produced a significant increase in [3H]flunitrazepam binding to the cortex, caudate/putamen and accumbens, and it tended to decrease the [3H]muscimol binding. These results suggest that the selective reduction of specific [3H]muscimol binding in the brain may be responsible, at least in part, for anxiety-related behavior in aged rats. Furthermore, it appears that the significant increase in specific [3H]flunitrazepam binding produced in the brains of aged rats by the long-term administration of KKT may be responsible for the anxiolytic effects of this agent. PMID- 7861668 TI - Role of the dopaminergic, serotonergic and cholinergic link in the expression of penile erection in rats. AB - The neural mechanisms underlying the penile erection induced by serotonergic, cholinergic and dopaminergic stimulants were comparatively investigated. Fenfluramine (0.1-10 mg/kg, i.p.), pilocarpine (0.032-3.2 mg/kg) and apomorphine (0.01-1 mg/kg) induced penile erection in rats with bell-shaped dose-response curves. The penile erection induced by fenfluramine (1 mg/kg) was dose dependently antagonized by pindolol (0.1-3.2 mg/kg), a 5-HT1 antagonist, or scopolamine (0.032-1 mg/kg), a muscarinic antagonist, but not by sulpiride (1-32 mg/kg), a dopaminergic antagonist. The penile erection induced by pilocarpine (0.32 mg/kg) was countered by pindolol or scopolamine but not by sulpiride, while that induced by apomorphine (0.032 mg/kg) was countered by all three antagonists. Septo-hippocampal cholinergic deafferentations by medial septum lesioning or fimbria-fornix transection also significantly attenuated the penile erection induced by fenfluramine or apomorphine, but scarcely affected that induced by pilocarpine. Raphe lesion by injections of 5,7-dihydroxytryptamine, a serotonergic neurotoxin, into the median- and dorsal-raphe nuclei significantly attenuated the penile erections induced by fenfluramine and apomorphine but not that by pilocarpine. These results suggest that a neuronal link between the dopaminergic, serotonergic and cholinergic systems plays a crucial role in the expression of penile erection; dopaminergic stimulation causes an activation of the raphe serotonergic neurons which in turn enhances the septo-hippocampal cholinergic pathway and results in expression of penile erection. PMID- 7861669 TI - Acetylcholine measurement of cerebrospinal fluid by in vivo microdialysis in freely moving rats. AB - Acetylcholine (ACh) and choline (Ch) levels in rat cerebrospinal fluid (CSF) were determined by in vivo microdialysis (CSF microdialysis) in both halothane anesthetized and freely-moving rats. The Ch/ACh ratio in CSF perfused with Ringer's solution (30 microliters/30 min) containing 10(-5) M physostigmine, a centrally active cholinesterase inhibitor, was significantly lower than that in unprocessed CSF due to significantly higher ACh levels in the former. The successive measurement on the 2nd and 7th day after the guide cannula implantation demonstrated the feasibility of the CSF microdialysis method for repetitive monitoring of CSF ACh and Ch levels in freely moving rats without extensive tissue damage. Intraperitoneal administration of physostigmine caused an increase in CSF ACh levels, whereas administration of neostigmine, which cannot penetrate into the blood brain barrier, did not. Furthermore, a centrally active acetylcholinergic M1-receptor agonist, AF102B, produced an increase in CSF ACh and Ch levels. Thus, the present study demonstrates that CSF microdialysis is a useful method for evaluating overall central cholinergic activity and investigating the pharmacological effects of various drugs that act via the central cholinergic system. PMID- 7861670 TI - Positive chronotropic and inotropic effects of higenamine and its enhancing action on the aconitine-induced tachyarrhythmia in isolated murine atria. AB - Aconitine and higenamine are the components of aconite root. We investigated the cardiac effects of these compounds on murine right and left atria and the interaction of higenamine with aconitine on the rate of spontaneously beating right atria. Higenamine increased the rate (EC50 = 38 nM) and the force of contraction (EC50 = 97 nM), the maximal responses being comparable with those of isoproterenol. The positive chronotropic effect of higenamine was antagonized by propranolol (30-300 nM) and practolol (10 nM-3 microM), but not by butoxamine (1 microM), indicating that it was a beta 1-adrenoceptor-mediated action. The positive chronotropic effect of higenamine was not changed by pretreatment with reserpine (4 mg/kg, i.p., 4 hr). Aconitine (0.16-0.25 microM) induced tachyarrhythmia in right atria was attenuated by quinidine (1 microM), atropine (8.6 microM) and AF-DX 116 (8.6 microM), suggesting that aconitine activates sodium channels and muscarinic receptors. Higenamine (2.5 nM) and dobutamine (1 nM) did not cause chronotropic effects by themselves, but enhanced the aconitine induced tachyarrhythmia. These results indicate that higenamine is a beta 1 adrenoceptor full agonist in murine atria and that the aconitine-induced tachyarrhythmia is augmented by the beta 1-adrenergic action of higenamine. PMID- 7861671 TI - Effects of benidipine on renal function in anesthetized spontaneously hypertensive rats. AB - Effects of benidipine on urine volume, excretion of electrolytes and renal hemodynamics were investigated in anesthetized spontaneously hypertensive rats (SHR). Benidipine at 3 and 10 micrograms/kg (i.v.) significantly increased urine volume, sodium (Na) and potassium (K) excretion with no change of creatinine clearance (CCRE). The increase in K excretion was relatively slight when compared with that in Na excretion. In another series of experiments, the tubular sites of action of benidipine were determined by the lithium clearance (CLi) technique and the stop-flow method. Benidipine at 3 micrograms/kg (i.v.) increased CLi, decreased creatinine concentration and increased Na concentration in the stop flow urine from the distal nephron. These results suggest that benidipine produces diuresis and natriuresis by the inhibition of water and Na reabsorption at both the proximal tubule and the distal nephron. Benidipine increased p aminohippuric acid clearance, but not CCRE, at doses of 3 and 10 micrograms/kg (i.v.), suggesting that benidipine dilates the glomerular efferent arteriole as well as the afferent arteriole. It is, therefore, expected that benidipine does not cause intraglomerular hypertension and has a beneficial effect in progressive renal disease. PMID- 7861673 TI - [Diurnal variation in passive avoidance response and serum corticosterone in rats]. AB - A possible relationship between diurnal variation in performance of step-through passive avoidance response (PAR) and that in adrenocortical response was investigated. In Wistar-Imamichi strain rats, retention latency of PAR and serum corticosterone (CORT) level immediately after retention test were measured as a function of time of day. Basal CORT level was found to be low during early phase of light period, and thereafter to elevate toward dark period (Exp. 1). Eighty animals were divided into eight groups, which consisted of a combination of two diurnal times of training/testing (light phase = 14:00 and dark phase = 2:00) and four shock intensities for training (0, 0.5, 0.75, 1.0 mA) (Exp. 2). The latency of PAR was found to be longer in the light than in the dark phase, and CORT markedly increased only in the light phase in the groups with 0.75 mA. In addition, PAR was conducted at four times of day (8:00, 14:00, 20:00, 2:00) with 0.75 mA shock (Exp. 3). It was confirmed that the diurnal variation of PAR latency was associated with that the CORT elevation, with the maximum at 14:00 and the minimum at 2:00. These results indicate that diurnal variation in performance of PAR has a close relationship with that in emotional or stress response to aversive situation. PMID- 7861672 TI - Antiallergic effect of ZCR-2060: antihistaminic action. AB - The antihistaminic effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060), a newly synthesized antiallergic agent, was investigated in both in vitro and in vivo studies. ZCR-2060 clearly antagonized histamine-induced contraction of isolated guinea pig ileum and trachea. In contrast, carbachol-, BaCl2- and 5-hydroxytryptamine-induced contractions of isolated guinea pig ileum were slightly inhibited by higher concentrations of ZCR 2060. 3H-Mepyramine specific binding to membranes from guinea pig lung and brain were markedly inhibited by ZCR-2060 in a concentration-dependent fashion. In the in vitro studies, the antihistaminic effect of ZCR-2060 was greater than those of cetirizine and terfenadine, but was less than that of ketotifen. In the in vivo studies, ZCR-2060 significantly inhibited the histamine-induced cutaneous reaction in rats, when administered orally 1 hr before the histamine injection. Moreover, ZCR-2060 has a long-lasting antihistaminic effect. In the in vivo studies, the antihistaminic effect of ZCR-2060 was found to be greater than that of cetirizine and terfenadine, and it was the same as that of ketotifen. Thiopental-induced sleep and spontaneous ambulatory activity in mice, however, were unaffected by ZCR-2060 at higher doses. These results indicate that ZCR-2060 has a potent, selective and long acting histamine H1-receptor antagonistic action without causing any unwanted CNS side effect. PMID- 7861674 TI - [Generation effect on implicit and explicit memory tasks: influence of instructions and proportion overlap of lists]. AB - The proportion of the words that were common to the study phase and the test phase was manipulated in two experiments. Subjects previously studied either 20% or 80% of the words appearing in the test. In Experiment 1, the subjects performed a word fragment completion test. In the 20% condition, reading words produced more priming than generating words. In the 80% condition, however, generating words produced priming as much as that of the 20% condition. Experiment 2 examined this proportion overlap effect on fragment cued recall test. The generation effect was observed in the 80% condition, but not in the 20% condition. These findings indicate that performance on memory tests is determined by the manipulations of both encoding and retrieval conditions. PMID- 7861675 TI - [A study on nonlinearity of the visual system in response to the flickering stimuli in the low temporal frequency domain]. AB - From different aspects than the frequency response analysis of the visual system, we investigated characteristics of the nonlinear response of the visual system to flickering stimuli in low temporal frequency domain. We measured increment threshold curves (masking functions) for 2 Hz flicker of rectangular and sawtooth waveforms, using six and three subjects, respectively. When the amplitude of the flicker was at a supraliminal level, the increment threshold curve had on transients for the rapid onset larger than off-transients for the rapid offset of the flicker wave. However, around a liminal amplitude level off-transients were more prominent. This result suggest that at low temporal frequencies (2 Hz) the temporal contrast sensitivity may be determined mainly by the 'off-responses' in the visual system. Moreover, we found the similar changes of increment threshold curves to the flicker stimuli for a single rectangular stimulus, which means that the results as above mentioned are not specific to the periodical stimuli. PMID- 7861676 TI - [Experimental test of a model of memory-representation-generation in learning and recognition]. AB - A highly structured set of stimuli was used in this study. Each stimulus had four binary attributes, whose values were determined so that any two stimuli could be transformed into each other by changing values of one or more attributes. In one experiment, 93 undergraduates rated similarity of paired stimuli. In another experiment, the same subjects learned three stimuli which were presented one after another for 10 seconds each. Later, in the recognition task, they made "old" or "new" judgment and rated the confidence of their judgment for each of the test stimuli. Two groups of subjects served the two experiments in different order. The results showed that (1) the rated similarity between the paired stimuli is a monotonically decreasing function of the number of transformations needed to get the pair equal, (2) the recognition confidence for new stimuli is significantly higher for stimuli generated by relevant transformations from the learned stimuli than for stimuli not so generated. The results support a model of memory-representation-generation (Suto, 1987, 1988), but not "prototype plus transformation model" nor "context model". PMID- 7861677 TI - [The influence of intertrial interval on learning of an isometric contractile task]. AB - The present study involved three motor learning experiments; Experiments 1 and 2 measured regulating grasping power and isometric elbow flexion power, respectively. Knowledge of Results (KR) was given after completion of a task of short duration. Experiment 3 was similar to Experiment 2, but procedurally, KR was given concurrently with the task. Accordingly, KR processing takes place within the intertrial interval and parallel to taking task in Experiments 2 and 3, respectively. In these experiments, influences of varying intertrial intervals on the learning process were examined. The results were as follows; 1) In Experiments 1 and 2, shortening of the intertrial interval caused a delay in learning, however this was not the case for Experiment 3. Insufficient KR processing time is considered to be partially responsible for the above delay, 2) In Experiment 3, lengthening of the intertrial interval caused the above delay. These results suggest motor information processing to involve a property of natural decay with the course of time. PMID- 7861678 TI - [Representation of letter position in visual word recognition process]. AB - Two experiments investigated the representation of letter position in visual word recognition process. In Experiment 1, subjects (12 undergraduates and graduates) were asked to detect a target word in a briefly-presented probe. Probes consisted of two kanji words. The latters which formed targets (critical letters) were always contained in probes. (e.g. target: [symbol: see text] probe: [symbol: see text]) High false alarm rate was observed when critical letters occupied the same within-word relative position (left or right within the word) in the probe words as in the target word. In Experiment 2 (subject were ten undergraduates and graduates), spaces adjacent to probe words were replaced by randomly chosen hiragana letters (e.g. [symbol: see text]), because spaces are not used to separate words in regular Japanese sentences. In addition to the effect of within word relative position as in Experiment 1, the effect of between-word relative position (left or right across the probe words) was observed. These results suggest that information about within-word relative position of a letter is used in word recognition process. The effect of within-word relative position was explained by a connectionist model of word recognition. PMID- 7861679 TI - [A developmental study of the effects of the contents of self-verbalization on the waiting behavior]. AB - The effects of overt self-verbalizations with different contents were examined developmentally with an experimental paradigm under which children were to resist temptation while waiting alone. Subjects, either four or six year old, were forbidden to touch attractive toys while the experimenter was out of the room, and were variously instructed to self-verbalize during the period. "Task oriented" subjects were to verbalize what they were told not to do. "Positive temptation-oriented" subjects were instructed to talk about the attractiveness of the forbidden objects. "Distraction" subjects were to verbalize irrelevant things to the waiting task. "Negative temptation-oriented" subjects were instructed to talk about the toys' unattractive aspects. No self-verbalization instruction was given to "No verbalization" subjects. Transgression latency was used as an index of waiting behavior. The results were as follows: (1) Positive temptation oriented did not affect the four-year olds' waiting behavior, but made waiting more difficult for the six-year olds'. (2) Task-oriented verbalization helped waiting behavior for both groups. (3) Neither distraction nor negative temptation oriented verbalization affected waiting behavior of either group. PMID- 7861680 TI - [The nature of intelligence in adults with Down syndrome: IQ distribution and sex differences]. AB - Normative data on intelligence in adults with Down syndrome was collected on 93 males and 80 females, aged 16 years and above, who had been given the Suzuki Binet Intelligence Scale. Both the male and female groups showed bimodal curves in the distributions of IQs. Only for the low IQ groups, the distributions were defined by binomial distributions. The mean ages of starting to walk for the low IQ groups were six months or more later than those for the high IQ groups. However, no significant differences were observed in birthweights, terms of pregnancy, and ages between the two groups. In addition, significant sex differences were found in mean IQs, females scored higher in both the two groups. PMID- 7861681 TI - [On the finger-drawing strategy in recognition of random shapes]. AB - The present study was designed to identify the memory-enhancing factor of finger drawing strategy, and investigate the relationship between finger-drawing and semantic processing of random shapes. Forty subjects were randomly assigned to one of the five conditions: imagery encoding, verbal encoding, finger-drawing for encoding, finger-drawing for searching, and finger-drawing for both encoding and searching, and performed recognition tasks of random shapes. Results indicated that in the two conditions under which finger-drawing was used for encoding, recognition of complex shapes was superior to that of simple ones. No differences were found for those of high and low associative shapes. Verbal reports of the subjects indicated that finger-drawing for encoding prevented them from naming the shapes. In contrast, in the other three conditions under which finger-drawing was not used for encoding, recognition of simple shapes was superior to that of complex ones. Also, recognition of high associative shapes was superior to that of low ones. These results suggest that kinetic representation, rather than amount of attention, is responsible for the memory-facilitating effect of finger drawing, and that finger-drawing for encoding inhibits active semantic processing. PMID- 7861682 TI - [The role of accident size in the risk-overestimation phenomenon]. AB - This experiment tested the hypothesis that the larger the size of aircraft accidents, the more overestimated the frequency of the accidents, as well as their associated risk. Ten descriptions of fatal accidents in which everyone died, and 30 of non-fatal ones in which several were injured, some seriously, were used as experimental stimuli. The independent variable was the size of fatal accidents. An average of 250 passengers were killed in the large disaster condition, while only 40 were killed in the small one, but the likelihood of death was kept constant across the size conditions. Subjects judged the frequencies of fatal and non-fatal accidents as well as the ratio of the former to the latter, rated risks associated with the airlines, and estimated as a manipulation check the average number of passengers in the stimulus descriptions. Results strongly supported the hypothesis. Subjects in the large disaster condition overestimated the frequency and risk of both fatal and non-fatal accidents. It was concluded that the stronger fear aroused in the large disaster condition heightened the availability of accident information, and resulted in the illusory correlation between the accident size and its associated risk. PMID- 7861683 TI - [Effects of repetitions in overt rehearsal on free recall]. AB - Two experiments were designed to separate the effects of oral repetitions from those of covert mental activity in over rehearsal on free recall. In both experiments, subjects were visually presented several lists of eight noun pairs one by one, with asterisks under the left or right noun of each pair. Subjects studied the lists by observing both nouns of each pair as well as by rehearsing aloud one noun with/without the asterisks. Each of the list presentation was followed by oral free recall test of both rehearsed and not-rehearsed nouns. It was expected that the difference of recall between rehearsed and not-rehearsed nouns would indicate the effects of the repetitions but not of the total rehearsal activity including the covert mental activity. In Experiment 1, the time lag between the study and the test was zero or 30 seconds. In Experiment 2, the time available for rehearsing each noun was four or eight seconds. The results suggest that the repetitions have only STM-maintenance function whereas the covert mental activity has only LTM-construction function. PMID- 7861684 TI - [The influence of conspecific distress responses on the lever choice behavior in the rat]. AB - We examined whether distress responses of rats would be a negative reinforcer or not. In Experiment 1, two rats were placed in adjacent compartments. One rat was reinforced by a food pellet for pressing either of two levers. One of the levers produced food while the other produced food plus electric shock (0.5-2.0 mA) to the other rat. All rats preferred the former lever. In addition, this tendency was more prominent in rats that had experienced shock previously than those without experience. In Experiment 2, one lever produced food while the other produced food plus auditory stimuli, a recorded distress scream (65 dB) or a pure tone (3 kHz, 65 dB). Rats that chose between food and food plus another rat's scream avoided being exposed to the scream. Rats that chose between food and food plus the pure tone chose the two levers equally. These results suggest that negative emotional responses of the conspecifics could be a negative reinforcer. PMID- 7861685 TI - [Response types to shock and avoidance learning in inbred strains of mice]. AB - The effects of shock intensity on response types to shock (Experiment 1) and the relationship between response types and avoidance learning (Experiment 2) were investigated in four inbred strains of mice (BALB/c, C3H/He, C57BL/6 and DBA/2J). In Experiment 1, mice received a one-second inescapable shock, which ranged in intensity from .01 to .4 mA (12 levels). Response types to shock were observed, and locomotion increased in all strains as the shock intensity increased. Additionally, the C3H/He strain also increased jumping response at shocks greater than .2 mA. In Experiment 2, the four strains were trained for shuttle avoidance with three shock intensities (.06, .16 and .4 mA). Two responses, locomotion into the adjacent compartment (L-typed) and rearing or jumping (R-typed), were equally effective in terminating the shock. While all strains learned the task at all the levels of shock intensities, the performance of the BALB/c strain declined as the intensity decreased. BALB/c and C57BL/6 strains avoided the shocks mainly by L typed response across all the intensities. Likewise, the DBA/2J strain predominately displayed L-typed responses, but some R-typed responses did occur. The C3H/He strain, on the other hand, largely avoided the shocks by the R-typed response, especially in the .06 and .4 mA conditions. PMID- 7861686 TI - [Effects of display and memory load on event-related potentials during a visual search task]. AB - We recorded event-related potentials (ERPs) in nine normal adult subjects to investigate the effects of display load (number of positions to be processed) and memory load (memory set size) on ERPs in visual search tasks. The stimulus consisted of a horizontal array of five different alphabets. In search task, subjects were required to respond only to stimuli containing a target letter. In a simple reaction task, they were required to respond to all the stimuli. The results showed that display load affected N200 and NA deflections recorded at occipital and posterior temporal electrodes, although memory load did not affect them. We also found the different effects of display load and memory load on search-related negativities. That is, in latency, search-related negativities with increasing display load appeared before those with memory load. The difference in topography between display and memory load effects on search related negativities was not confirmed statistically. The validity of ERPs as indices for the visual and memory search processes was discussed. PMID- 7861687 TI - [The effect of stressor experiences and optimism upon stress responses]. AB - The present studies investigated whether or not optimism/pessimism is a cognitive mediator of future depression for people who have experienced many negative life events. Subjects were administered optimism scales, stress response scales at Time 1. They then completed the stressor scale and stress response scales at Time 2, about six weeks later. The results showed the interaction of stressor experiences and optimistic diathesis: Subjects who have higher stressor experiences and higher stable and global explanatory style for negative events showed higher depressive responses. Other indices of optimistic diathesis--Life Orientation, Cognitive Style, and Internality dimension of Attributional Style- did not produce this interaction effect. Moreover, this interaction did not appear in the psychological stress response other than depression. These results were consistent with diathesis-stress model of depression. PMID- 7861688 TI - Diagnosis of patients with syncope in emergency medicine. AB - Syncope is a common medical problem, which accounts for 3.5% of emergency room visits. It includes diverse clinical etiologies, from cardiac origin with poor prognosis to reflex-mediated hypotension with benign clinical course. Trauma is not rare in patients with syncope, e.g. bruises or lacerations on the head and face were recognized in 17%. Accordingly, patients presenting with syncope may have a risk of sudden cardiac death, or risk of trauma if the episodes are repetitive. It is a physicians's task to diagnose syncope and identify its cause. The history is an essential part of the initial evaluation. Electrocardiography (ECG) is necessary in every case. However, organic disease as a cause is identified in 20% of syncope in routine work-up, and the remaining cases are reflex induced hypotension (neurocardiogenic syncope), misdiagnosed arrhythmia, coronary spasm or unknown. Recent investigations suggest the usefulness of provocation to diagnose neurocardiogenic syncope. Two important non-invasive provocations to reproduce syncope are carotid sinus compression and tilt table test. In patients with syncope who visited emergency room, tilt test was positive in 25%, whereas the response to carotid sinus compression was positive in 21%. One or both of the tests was positive in 39%, suggesting that neurally-mediated syncope accounts for a significant number of patients. PMID- 7861689 TI - Pharmacotherapy of schizophrenia: the American current status. AB - This is a review paper covering the American current status of pharmacotherapy of schizophrenia. The author lists all available antipsychotic agents on the market in the United States and describes the American prescribing pattern of antipsychotic agents. This includes a brief history of antipsychotic use in America, acute treatment and chronic maintenance with antipsychotic drugs, the recent advent of atypical antipsychotic agents, and management of antipsychotic induced side-effects. The characteristics of prescribing American antipsychotics in America are described, and they are then compared with Japanese prescribing practices. The author also makes brief remarks about the uncovered issues in antipsychotic pharmacotherapy and about atypical antipsychotic agents in the context of the future pharmaceutical development. PMID- 7861690 TI - Respiratory syncytial virus and allergic conjunctivitis. AB - The pathogenesis of allergic conjunctivitis is largely conjectural. We investigated the possible involvement of respiratory syncytial virus (RSV), a ubiquitous respiratory pathogen, in the development of allergic conjunctivitis through immune mechanisms. Brush cytology technique was used to obtain conjunctival cells from 30 patients with allergic conjunctivitis and 20 controls. Samples were assayed for the presence of RSV sequences with the reverse transcription polymerase chain reaction (RT-PCR) and the nested polymerase chain reaction (nested PCR). In order to further investigate the relation of RSV and allergic conjunctivitis, we performed an animal study. BALB/c mice were either infected with live RSV or sham infected intranasally. The mice were exposed to ovalbumin (OVA) with alum adjuvant. At differing intervals, levels of OVA concentration in serum and IgG-anti-OVA antibody were measured by ELISA and IgE anti OVA antibody in serum was assessed by passive cutaneous anaphylaxis. RSV sequences were detected in 7 (23%) of 30 patient samples and 1 (5%) of 20 control samples. IgG and IgE antibody responses to OVA in serum were demonstrable only in RSV-infected mice immunized with OVA and alum. Our results proved that PCR could detect RSV sequences in conjunctival samples. RSV may be a significant pathogenic factor in allergic conjunctivitis. PMID- 7861691 TI - Spastic paraplegia with amyotrophy of the legs: a rare case of motor and sensory neuropathy. AB - A 36-year-old man who suffers from gait disturbance is reported. He noticed deformity of his feet at the age of 15. When he was 32 years old, he complained of heaviness in his lower extremities. Since then his legs have been always stiff. He had no previous illness or familial neuromuscular diseases. Neurological examination revealed no impairment of mental function or cranial nerves. Marked weakness and wasting of the feet were noted. The legs showed an inverted champagne bottle shape and pes cavus deformity was evident. Deep tendon reflexes were normal in the arms but abnormally brisk in the legs. Bilateral Babinski sign and ankle clonus were elicited. The patient tended to walk on his toes and the legs scissored. The motor nerve velocities were less than normal. Sural nerve biopsy showed reduced myelinated fiber density and increased endoneurial connective tissue. Electron microscopy showed axonal swellings filled with neurofilaments. Distal wasting and weakness involving the legs more than the arms resembled that of Charcot-Marie-Tooth disease. According to the classification by Dyck, this disorder could be referred to as hereditary motor and sensory neuropathy type V. Spastic paraplegia with amyotrophy is rare, but should be identified as a distinct disorder. Recognition of this disorder would imply the clinical and genetic heterogeneity of Charcot-Marie-Tooth disease. PMID- 7861692 TI - Advances in genome research and molecular diagnostics. AB - A diverse scala of refined molecular techniques, developed during early positional cloning and the Human Genome project, has caused a rapid increase of our insight into the cause of genetic diseases. Nowadays, from cytogenetic rearrangements to point mutations can be readily detected by a variety of techniques. This not only has broadened our understanding, but has also enormously assisted in providing rapid and specific diagnosis, hence reducing uncertainty and improving the choices for those concerned with genetic disease in their family. While initially restricted to the DNA-level, diagnostic technology has gradually been tailored to suit the specifics of the diseases in question, incorporating RNA and protein analysis. The latest development in the analysis of genetic disease is reviewed. PMID- 7861693 TI - A case of gastrin secreting islet cell carcinoma with multiple liver metastasis and repeated gastric bleeding. PMID- 7861694 TI - Trapidil inhibits human mesangial cell proliferation: effect on PDGF beta receptor binding and expression. AB - Mesangial cell (MC) proliferation, a histopathologic feature common to many human glomerular diseases, is regulated by several growth factors through their binding to specific cell surface receptors. Platelet-derived growth factor (PDGF) is a peptide exerting a potent mitogenic activity on MC. Recently, an increased expression of both PDGF protein and its receptor has been localized in the mesangial areas of several experimental as well as human proliferative glomerulonephritides (GN). Thus, it may be postulated that the inhibition of PDGF action could prevent MC proliferation during mesangial proliferative GN. Trapidil, an antiplatelet drug, has been shown to inhibit the growth of several cell types both in vitro and in vivo. The present study was aimed at evaluating the effect of Trapidil on human MC in vitro. The addition of 100 to 400 micrograms/ml Trapidil significantly reduced cell proliferation induced by different growth factors (FCS, PDGF-BB, bFGF, EGF), the highest inhibitory effect being on PDGF-BB stimulated MC growth. The effect of the drug was dose-dependent and seemingly specific: aspirin was devoid of any anti-proliferative action, while dypiridamole proved to be toxic. Receptor binding experiments showed that Trapidil competitively inhibited 125I-PDGF-BB binding to its cell surface receptors, without inducing receptor internalization, at least after short-term (2 hr) incubation. In contrast, long-term (48 hr) exposure to 400 micrograms/ml Trapidil caused a sharp increase of PDGF-BB binding. Similar effects on cell proliferation and 125I-PDGF-BB binding were observed when NIH-3T3 fibroblasts were exposed to the test substance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861695 TI - Radiotelemetric BP monitoring, antihypertensives and glomeruloprotection in remnant kidney model. AB - The mechanisms by which antihypertensives exert a glomeruloprotective effect in the remnant kidney model remain controversial. Based on periodic tail-cuff BP measurements, the variable glomeruloprotective efficacy of antihypertensive agents has been ascribed to mechanisms other than or in addition to their ability to lower BP. To more precisely define the relationship between BP control and glomeruloprotection, systolic BP was continuously monitored radiotelemetrically at 10-minute intervals for approximately 65 days in rats after approximately 5/6 renal ablation. Rats with remnant kidneys received either no therapy or one of three antihypertensive regimens in their drinking water after the first week: enalapril, a triple therapy regimen (reserpine, hydralazine, hydrochlorothiazide); or a high dose triple therapy regimen. Although all antihypertensive regimens significantly lowered BP, considerable interanimal variability was observed. Additionally, marked lability of BP was present in both untreated and treated rats. Glomerular injury in individual animals (N = 34) was very strongly correlated with their overall averaged systolic BP during the final eight weeks (r = 0.91) and with the frequency of systolic BP readings > 150 mm Hg (r = 0.89). These data do not provide evidence of a therapeutic advantage for any of the regimens independent of their antihypertensive effects but indicate that the glomeruloprotective efficacy of these antihypertensive regimens is directly proportional to their antihypertensive efficiency. PMID- 7861696 TI - High glucose and TGF beta 1 stimulate fibronectin gene expression through a cAMP response element. AB - Previously, we reported that mesangial cells increased fibronectin, laminin and type IV collagen synthesis when cultured in the presence of high glucose (30 mM). Although mRNA levels for all three extracellular matrix (ECM) proteins were also increased in high glucose conditions, the mechanism for this increase was not known. In order to determine whether increased transcription was involved in the observed increase in fibronectin mRNA levels mesangial cells were transfected with a construct containing the 5'-flanking region of the fibronectin (FN) gene [position +69 to -510 base pairs (bp)] fused to the coding region of the chloramphenicol acetyltransferase (CAT) gene [FN-CAT (-510)]. Cells were transiently and stably transfected with this construct. Under serum-free conditions, high glucose increased CAT activity only in the presence of TGF beta 1 (referred to as TGF beta). The experiments were performed without serum because FN-CAT (-510) contains a serum responsive element. The increase in CAT was approximately twofold in transiently transfected cells and threefold in stably transfected cells. TGF beta alone increased CAT activity approximately 30%. Stimulation of fibronectin gene expression appeared to occur at the level of a cAMP response element (CRE) located -170 bp of the FN gene because cells transfected with a construct containing an oligonucleotide encoding for this CRE fused to a minimal fibronectin promoter (-56 bp) and a CAT reporter gene [CRE ( 170) FN-CAT] displayed similar increments of CAT activity after treatment with high glucose and TGF beta. Gel shift mobility assays with a CRE oligonucleotide revealed multiple complexes with mesangial cell nuclear proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861697 TI - Polymorphonuclear leukocytes increase glomerular albumin permeability via hypohalous acid. AB - Acute glomerulonephritis is characterized by the presence of neutrophils within glomeruli and the generation of reactive oxygen species (ROS) by activated polymorphonuclear leukocytes (PMNs). Hydrogen peroxide (H2O2) and other ROS including hypothalous acids have been implicated in PMN mediated injury. To determine the role of specific ROS in PMN mediated glomerular injury, isolated rat glomeruli were incubated for 30 minutes at 37 degrees C with H2O2, with H2O2 and myeloperoxidase, or with activated PMNs. Scavengers of ROS were included in some experiments. PMNs were harvested from rat peritoneal cavity and activated with phorbol myristate acetate (PMA). Glomerular albumin permeability (Palbumin) was calculated from the volume response to an oncotic gradient. Palbumin of glomeruli incubated with H2O2 (10(-3) or 10(-1) M) was not increased, while Palbumin after incubation with H2O2 and MPO was markedly increased (0.94 +/- 0.004). Palbumin after incubation with PMA, or with non-activated PMNs was not different from that of control glomeruli, Palbumin of the glomeruli incubated with activated PMNs increased (0.85 +/- 0.01, P < 0.001). This increase in Palbumin was inhibited by superoxide dismutase, catalase, or taurine (Palbumin = 0.035 +/- 0.06, -0.39 +/- 0.10, 0.028 +/- 0.06, respectively) and ameliorated by sodium azide (Palbumin = 0.21 +/- 0.03). In contrast, dimethyl sulfoxide did not prevent the increase in Palbumin (Palbumin = 0.92 +/- 0.01). Our results show that the hypohalous acid derived from that of H2O2-MPO-halide system is capable of increasing Palbumin. We conclude that hypohalous acid may be the primary mediator of the immediate increase in glomerular protein permeability induced by PMNs. PMID- 7861698 TI - Cyclic RGD peptides ameliorate ischemic acute renal failure in rats. AB - Renal tubular obstruction is an important contributor to the pathophysiology of acute renal failure. Based on the previous findings of the role played by arginine-glycine-aspartic acid (RGD) recognizing integrins in tubular obstruction, this study examined the effect of RGD peptides on the course of ischemic acute renal failure in rats. For in vivo studies, animals were subjected to 45 minutes of unilateral renal ischemia with contralateral nephrectomy, and cyclic RGD peptides or a linear biotinylated RGD peptide were injected systemically after the release of renal artery clamp. In vitro studies compared the potency of the peptides in inhibiting BS-C-1 cell-matrix and cell-cell adhesion. Two novel cyclic RGD peptides utilized in these studies showed different inhibitory potency in preventing cell-matrix adhesion: cyclic RGDDFV was a highly potent in vitro inhibitor of BS-C-1 cell-matrix adhesion, whereas cyclic RGDDFLG was less potent. In cell-cell adhesion assays, however, both peptides were equipotent. Despite the differences in inhibiting cell-matrix adhesion, a single systemic administration of either peptide improved creatinine clearance postoperatively and accelerated recovery of renal function with a rank order: cyclic RGDDFV > or = RGDDFLG >> RDADFV (inactive control). These findings represent the first in vivo demonstration of the effectiveness of cyclic RGD peptides in ameliorating ischemic acute renal failure, and suggest that in this setting RGD peptides predominantly inhibit cell-cell adhesion, whereas inhibition of cell-matrix adhesion is of lesser significance. PMID- 7861699 TI - Role of protein kinase pathways in IL-1-induced chemoattractant expression by human mesangial cells. AB - Human mesangial cells produce the monocyte-specific chemotactic factor monocyte chemoattractant protein-1 (MCP-1) in response to a variety of stimuli, including the pro-inflammatory cytokine interleukin-1 beta (IL-1). The intracellular signals responsible for mediating the effects of IL-1 on MCP-1 expression in human mesangial cells have not been defined. Evidence from other types of cells suggests that protein kinases are involved in MCP-1 gene regulation. We investigated the role of protein kinase pathways in mediating IL-1-induced MCP-1 expression. Activation of protein kinase C (PKC) by phorbol esters or diacyglycerol up-regulated mesangial MCP-1 message and bioactivity in a fashion similar to IL-1. However, while inhibition of PKC activity completely blocked phorbol-induced MCP-1 up-regulation, induction by IL-1 was not prevented. Inhibitors of cyclic AMP (cAMP)-dependent protein kinase (PKA) also failed to block IL-1-induced MCP-1 expression. Furthermore, increasing intracellular cAMP and activating PKA attenuated basal MCP-1 mRNA levels by 82% and blocked IL-1 induced MCP-1 expression by 88%. Finally, the role of protein tyrosine kinases was studied. The structurally distinct protein tyrosine kinase (PTK) inhibitors genistein, herbimycin A, and tyrphostin each caused a dose-dependent inhibition of the effects of IL-1 on mesangial MCP-1 activity. IL-1 treatment of mesangial cells resulted in the up-regulation of three tyrosine phosphoproteins with apparent molecular masses between 40 and 62 kD. These results suggest that the effects of IL-1 on MCP-1 expression are not mediated through PKC or cAMP-PKA, but may be transduced through PTKs. PMID- 7861700 TI - PGF2 alpha activation of Na/H antiporter and ammoniagenesis in parent/variant LLC PK1 cells. AB - A novel variant of the LLC-PK1 cell line was used to examine directly the mechanism whereby PGF2 alpha and TPA inhibit renal ammoniagenesis. The variant cells, which exhibit a growth pattern and morphology similar to the parent cell line, were isolated by a self selection process utilizing long-term cultures of parent cells maintained under conditions of continuous gentle rocking of the media fluid. Incubation of both parent and variant LLC-PK1 cells for one hour in a glutamine supplemented Krebs-Hensleit media of low pH (pH 6.8) increased ammonia and alanine production in comparison to the basal rates at pH 7.4. The phorbol ester TPA and also PGF2 alpha inhibited the low pH-induced increases in ammonia and alanine formation in parent cells; however, neither TPA nor PGF2 alpha inhibited ammonia or alanine metabolism in variant cells. TPA and PGF2 alpha activated PKC similarly in the parent and variant cells as demonstrated by a significant increase in membrane bound enzyme activity. BCECF labeling of cells indicated that the parent and variant cells possess an amiloride sensitive Na+/H+ antiporter of comparable activity. Exposure of parent cells to PGF2 alpha or TPA resulted in the activation of Na+/H+ antiporter activity. By contrast, neither compound stimulated antiporter activity in variant cells. These studies strongly suggest that PKC mediated activation of the Na+/H+ antiporter accounts for the inhibition of ammonia production produced by both PGF2 alpha and TPA. In addition, this novel variant of LLC-PK1 cells should provide a valuable tool to investigate various normal and pathophysiological functions involving mediation by PKC and/or Na+/H+ antiporter activity. PMID- 7861701 TI - Thromboxane stimulation of mesangial cell fibronectin synthesis is signalled by protein kinase C and modulated by cGMP. AB - Thromboxane (TX) has been implicated in the pathogenesis of glomerulosclerosis in several models of glomerular injury. In the present study, we examined the role of the protein kinase C (PKC) signalling system in expression of the action of the TXA2/PGH2 analogue U-46619 to stimulate fibronectin (Fn) synthesis in cultured rat mesangial cells (MC), and the influence of cGMP on this MC response. U-46619 activated PKC and enhanced Fn synthesis in MC in a time and concentration dependent fashion. Both responses to U-46619 were blocked by GF 109203X, a selective inhibitor of PKC activity, as well as by calphostin C and staurosporine, PKC inhibitors structurally distinct from GFX. Down-regulation of PKC by prior sustained exposure of MC to 0.5 microM phorbol myristate acetate similarly blocked increases in Fn synthesis induced by U-46619. The TXA2/PGH2 receptor antagonist Sq-29548 also prevented activation of PKC and stimulation of Fn synthesis by U-46619, consistent with transduction of these responses via specific high affinity TXA2/PGH2 receptors on MC. Addition of exogenous 8-Br-cGMP or stimulation of endogenous cGMP generation with atrial natriuretic peptide (ANP) suppressed both U-46619 activation of PKC and stimulation of Fn synthesis. cGMP did not alter TXA2/PGH2 receptor number of affinity in MC, but significantly suppressed phorbol ester activation of PKC. Thus, cGMP inhibition of U-46619 actions is expressed at steps distal to TX receptor binding and may involve effects at and proximal to activation of PKC. Interactions between the PKC and cGMP cellular signalling systems may be important determinants of MC matrix protein production in response to TX. PMID- 7861702 TI - Binding to and killing of human renal epithelial cells by hemolytic P-fimbriated E. coli. AB - Acute pyelonephritis is a common invasive infection frequently caused by E. coli that possess P-fimbriae and secrete hemolysin. We have examined the role of P fimbriae and hemolysin in the killing of putative target cells of acute pyelonephritis, that is, human renal epithelial cells (HRPTEC). Cultures of HRPTEC were overlaid with (1) a prototypic pyelonephritogenic E. coli (CFT073) which expresses both P fimbriae and hemolysin; (2) its hemolysin-negative isogenic mutant (CFT073hlyD::TnphoA); or (3) a prototypic nonpyelonephritogenic fecal E. coli (FN414) which is negative for both P fimbriae and hemolysin. CFT073 and CFT073hlyD::TnphoA but not FN414 adhered to HRPTEC, as demonstrated by electron microscopy and direct counting. Adherence was diminished by antisera directed against P fimbriae and by a monoclonal antibody recognizing the epithelial receptor for P fimbriae. CFT073 was significantly more cytolethal for HRPTEC than its hemolysin-negative mutant. The bacteria-free filtrate of CFT073 was both hemolytic and cytolethal whereas that of CFT073hyD::TnphoA was not hemolytic and was significantly less cytolethal. Finally, we demonstrated that CFT073 passed through monolayers of HRPTEC at a higher rate than CFT073hlyD::TnphoA, indicating that hemolysin damages HRPTEC, facilitating passage of bacteria through the epithelial barrier. With HRPTEC and a pyelonephritogenic strain of E. coli we have reproduced in vitro bacterial attachment and toxin delivery by P fimbriae and hemolysin, factors epidemiologically associated with acute pyelonephritis in patients. PMID- 7861703 TI - Potassium and sodium transport along the loop of Henle: effects of altered dietary potassium intake. AB - We assessed the effects of changes in potassium (K+) balance on the function of the loop of Henle by a combination of renal clearance and microperfusion experiments. Rat superficial cortical nephrons were perfused in vivo at 20 nl.min 1 from late proximal to early distal tubule with an artificial end-proximal solution containing either 3.8 or 1.8 mM potassium. Rats were fed a control diet, a low-potassium diet for at least three weeks, or a high-potassium diet for 10 to 14 days. When compared with the appropriate end-proximal potassium concentration in the perfusion fluid, potassium absorption along the loop of Henle (JK) increased in potassium-depletion whereas sodium (JNa) and fluid (Jv) absorption decreased. In rats fed a high-potassium diet, absorption of potassium, sodium and fluid was depressed. We propose that changes of external potassium balance affect the transport of electrolytes and fluid along the loop of Henle in vivo by modulating the transport of potassium and sodium primarily in the thick ascending limb. Changes in potassium reabsorption may also be affected by alterations of potassium-recycling. PMID- 7861704 TI - Mechanisms of polymorphonuclear leukocyte mediated peritoneal mesothelial cell injury. AB - To determine the susceptibility of human peritoneal mesothelial cells to injury mediated by activated polymorphonuclear leukocytes (PMNs), we exposed cultured human peritoneal mesothelial cells to 1250, 2500, 3750, and 5000 PMNs/mm3 activated with 50 ng/ml phorbol myristate acetate (PMA) or with 10(-7) FMLP/cytochalasin B for one to five hours. PMN adhesion to mesothelial cells was determined with radiolabeled PMNs. Mesothelial cell injury was determined in five different cell lines by measuring ATP depletion and 51chromium release. In each mesothelial cell line, PMN adhesion was significantly (P < 0.001) increased when PMNs were activated; 64 +/- 1.0 to 92.5 +/- 7.0% of the activated PMNs were adherent to mesothelial cells compared to 6 +/- 1.8 to 27 +/- 2.4% of resting PMNs. Mesothelial cells responded to PMN mediated injury with a fall in ATP levels and 51chromium release that was significant (P < 0.05) by three to four hours. At five hours, ATP levels were markedly depressed to 5 to 41% of control values. Increasing concentrations of activated PMNs caused significantly (P < 0.05) greater mesothelial cell injury as determined by ATP depletion and 51chromium release. PMN adhesion, ATP depletion and 51chromium release were significantly (P < 0.01) prevented by an anti-CD18 monoclonal antibody that inhibits the CD11/CD18 adhesion molecule complex on PMNs. Similar injury and protection from injury was demonstrated when mesothelial cells were exposed to PMNs activated with FMLP/cytochalasin B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861705 TI - Reduction of functioning parathyroid cell mass by ethanol injection in chronic dialysis patients. AB - Recent data suggest that the larger parathyroid glands are more resistant to calcitriol therapy than the smaller glands due to more severe reduction of calcitriol receptor number. To control severe secondary hyperparathyroidism resistant to calcitriol pulse therapy in chronic dialysis patients, we introduced repeatable and quantitative ethanol injection(s) into the largest parathyroid gland under ultrasonographic guidance with a specifically modified needle. Efficacy of each injection and the recurrence of hyperparathyroidism were confirmed by color Doppler ultrasonography and could undergo additional ethanol injection(s) into the optimal site. When the ethanol injection(s) into the largest gland was not sufficient to control PTH hypersecretion, we injected ethanol into the next largest gland. We performed 32 injections into 16 parathyroid glands in nine dialysis patients. PTH decreased to less than 200 pg/ml after the final injection in seven patients and they remained controlled either by the following conventional oral active vitamin D or calcitriol pulse therapy. The other two patients, whose PTH decreased but not to less than 200 pg/ml, also became controllable with the following calcitriol pulse therapy. Recurrent nerve palsy was encountered in 2 out of 32 injections, but only transiently. Our data suggest that the measurement of the size of parathyroid glands is an important factor in the management strategy of secondary hyperparathyroidism in chronic dialysis patients, and that ethanol injection(s) into the largest parathyroid gland(s) could be an effective and safe strategy to restore the responsiveness to calcitriol therapy, by reducing the functioning parathyroid cell mass most resistant to calcitriol. PMID- 7861706 TI - Differences in hormonal and renal vascular responses between normotensive patients with autosomal dominant polycystic kidney disease and unaffected family members. AB - We tested the hypothesis that overactivity of the renal and systemic renin angiotensin system is important to the pathogenesis of hypertension in autosomal dominant polycystic kidney disease (ADPKD). Up to 21 normotensive subjects with ADPKD and creatinine clearance > 70 ml/min/1.73 m2 were compared to 12 unaffected controls from the same families. Blood pressure, serum chemistry, sodium excretion, plasma renin and serum aldosterone and atrial natriuretic peptide (ANP) levels were measured at baseline, after acute sodium depletion, and after chronic higher sodium intake with and without enalapril. Effective renal plasma flow was measured by paraaminohippurate clearance in the higher sodium state, before and during an intravenous infusion of angiotensin II at 3 ng/kg/min. This was to test whether, by analogy to non-modulating essential hypertension, renal blood flow would fall to a lesser extent in the ADPKD subjects. The groups were comparable at baseline apart from a higher supine mean arterial pressure in the ADPKD group (median 91 vs. 81 mm Hg, P = 0.002). There were no significant differences between ADPKD and control subjects in blood pressure or hormonal response to sodium depletion. During chronically higher sodium intake, serum ANP was significantly higher (median 130 vs. 81 ng/liter, P = 0.0006) and plasma renin tended to be higher (median 20.5 vs. 13.5, P = 0.08) in ADPKD than in control subjects. The ADPKD group had a higher renal vascular resistance (median 7420 vs. 5915 dyn.sec.cm-5, P = 0.009) before angiotensin, but tended to have a lower percentage rise in resistance during angiotensin (median 31.5 vs. 46, P = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861707 TI - Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol. AB - The aim of this study was to assess the effect of a long-term course of high-dose i.v. pulses of calcitriol (CLT) on hyperparathyroid bone disease (HBD) and functional mass of parathyroid glands of chronically hemodialyzed uremic (CHU) patients. We prospectively studied nine CHU patients treated with CLT, 30 ng/kg/body wt, i.v., thrice weekly over a period of eight months. Plasma concentrations of intact parathyroid hormone (iPTH), bone GLA protein (bGLA) and bone isoenzyme of alkaline phosphatase (biALP) were sampled throughout. Transiliac bone biopsies were made before and after the start of CLT therapy. Double scanning scintigraphy of the neck with 201Tl-99Tc was made before, during and eight months after the start of the treatment. All patients but one, who later responded to higher than planned CLT doses, had significant decreases of plasma iPTH (F = 76; P < 0.0001; ANOVA). The mean pretreatment value of PTH was 966 +/- 160 (mean +/- SE) pg/ml and it had decreased significantly by the first week (T = 2.4, P < 0.04), and had fallen an average of 80% by the 35th week. Ionized plasma calcium concentration was 1.19 +/- .01 mmol/liter which rose significantly (F = 13.5; P < 0.0001) by the 14th week to maximal peak levels, averaging 1.34 +/- .02 mmol/liter. Changes in biALP were parallel to those of iPTH, while bGLA tended to increase immediately after the start of the therapy and to significantly decrease thereafter (T = 3.2; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861708 TI - Urinary sodium to potassium ratio and urinary stone disease. The Gubbio Population Study Research Group. AB - The relation was investigated of urinary sodium to potassium ratio in first morning voided urine (spot urine) to urinary stone disease in 3,625 men and women aged 25 to 74 years participating in the baseline examination of the Gubbio Population Study. History of urinary stone disease (excretion of stone, and/or radiographic or ultrasonic evidence of urinary stone, and/or operation for urinary stone removal) was reported by 127 individuals (3.50%). Prevalence of urinary stone disease was lower in women than in men (2.59 and 4.58%, P < 0.001) and positively related to age (P < 0.001). Compared to nonstone formers, stone formers (N = 127) had higher urinary sodium to potassium ratio (P < 0.01), with similar plasma potassium and sodium concentration. In both sexes, urinary stone disease was positively related (P < 0.001) to sodium to potassium ratio: quartile analysis of this ratio showed that prevalence of stone formers in quartile 4 compared to quartile 1 was 3.33 times higher in women (P < 0.005, 95% confidence interval 1.36/8.60) and 2.71 times higher in men (P < 0.004, 95% confidence interval 1.35/5.93). In multiple logistic regression, urinary stone disease was significantly related to age, sex, and urinary sodium to potassium ratio (P < 0.01), controlled for other possible confounders, with or without exclusion of stone formers with plasma creatinine > 1.20 mg/dl. In an alternative model, with urinary sodium to potassium ratio not included, urinary stone disease was positively related to urinary sodium to creatinine ratio (P < 0.001) and weakly (P = 0.079) related inversely to urinary potassium to creatinine ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861709 TI - Membrane adsorption of beta 2-microglobulin: equilibrium and kinetic characterization. AB - Enhanced extracorporeal removal of beta 2-microglobulin (beta 2m) may prevent the development of dialysis-related amyloidosis (DRA). One mechanism of beta 2m removal is membrane adsorption. Therefore, we fundamentally characterized beta 2m adsorption to the highly permeable polyacrylonitrile (PAN) membrane. Porous and nonporous PAN fragments were incubated in buffer containing 125I-beta 2m. Over a concentration range of 8 to 60 mg/liter, the equilibrium adsorption isotherm was linear (r = 0.99) for porous PAN while the isotherm for nonporous PAN suggested either multilayer binding or adsorption of proteins with differing orientations. In kinetic analyses, the approach to equilibrium versus (time)1/2 was evaluated. For both porous and nonporous PAN, this relationship was linear (r = 0.99), consistent with a diffusion-controlled process. Adsorption reversibility was assessed by comparing the amount bound at varying residence times (0 to 4 hr) to the amount remaining adsorbed after a subsequent incubation in buffer. The fractions remaining bound at 60, 120, and 240 minutes (0.34 +/- 0.02, 0.36 +/- 0.06, and 0.44 +/- 0.03; mean +/- SEM) were significantly greater (P < 0.05) than the value at five minutes (0.23 +/- 0.01). This suggests membrane-induced conformational changes in adsorbed beta 2m. This investigation permits the comparison of beta 2m adsorptive properties of PAN to those of other membrane based and nonmembrane-based therapies designed to prevent DRA. PMID- 7861710 TI - Cholesteryl ester transfer in patients with renal failure or renal transplants. AB - Plasma newly-synthesized cholesteryl ester transfer (NCET) rate and concentrations of lipids, lipoproteins and apolipoproteins A1 and B were measured in chronic renal failure patients (dialysis independent and dialysis dependent), patients with a functioning renal transplant and in healthy control subjects with comparable ages and plasma triglycerides. Plasma NCET rates and apoB concentrations were significantly higher in patients treated by continuous ambulatory peritoneal dialysis (CAPD) compared with controls. In normolipidemic subjects (cholesterol < 6.5 mmol/liter, triglycerides < 2.0 mmol/liter), plasma NCET rates did not differ significantly from rates in the corresponding control subjects. In hyperlipidemic subjects, plasma NCET rates were significantly higher than rates in the normolipidemic subgroup. Plasma NCET rates were correlated closely with plasma apoB levels in all renal patients combined (r = 0.754, N = 53, P < 0.001) and with plasma cholesteryl ester mass transfer (r = 0.853, N = 13, P < 0.001). We conclude that, in the absence of hyperlipidemia, plasma NCET rate is normal in patients with chronic renal failure irrespective of the treatment for uremia, and when hyperlipidemia is present NCET rates are raised and may contribute to elevated levels of the proatherogenic apoB-containing lipoproteins. PMID- 7861711 TI - Plasma prorenin as an early marker of nephropathy in diabetic (IDDM) adolescents. AB - We studied a group of 50 adolescents, average age 16 years, with diagnosed IDDM present for about seven years. Twenty-five had microalbuminuria (MA) averaging 111.0 +/- 34.0 (SEM) micrograms/min albumin excretion rate versus 6.7 +/- 7.4 micrograms/min in the 25 without MA. In other respects, such as sex ratio, age, body mass index, duration of IDDM, hemoglobin A1c, and normotensive systolic, diastolic and mean blood pressures (BP), these subgroups were closely matched. We compared them with a control group of 39 normotensive adolescents, of whom 18 were carefully matched siblings of the IDDM subjects with MA and 21 were similarly matched siblings of the IDDM non-MA subjects. Plasma renin concentration was determined by a direct radioimmunoassay method (Sanofi-Pasteur) and found to be virtually the same in the control and IDDM adolescents as a whole. There was also no real difference between the MA and non-MA subgroups. In contrast, plasma prorenin was significantly higher in the combined IDDM group (197.5 +/- 9.3 vs. control, 134.0 +/- 7.9 pg/ml, P < 0.0001). It was also higher in the MA subgroup than in the non-MA subgroup (226.4 +/- 13.6 vs. 168.5 +/- 10.1 pg/ml, P < 0.001). Interestingly, the 18 control siblings matching the MA subgroup had higher plasma prorenin than the 21 control siblings matching the non MA subgroup (P < 0.001), suggesting a familial predisposition that precedes detectable diabetes and nephropathy. Our findings confirm and extend reports by other workers that elevated plasma prorenin is associated with incipient nephropathy, manifested by MA. The exclusive renal origin of this prorenin, its role in plasma, and the mechanism responsible for its elevation in IDDM with MA, are yet to be demonstrated, as is the general applicability of these findings to different populations of diabetics, with a higher incidence and severity of complications. PMID- 7861712 TI - Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy. AB - Intermittent calcitriol therapy is commonly used to treat secondary hyperparathyroidism in patients undergoing regular dialysis, but there is little available information about the histologic response of bone to this form of therapy. Accordingly, 14 children and adolescents with biopsy-proven secondary hyperparathyroidism were treated with intermittent oral or intraperitoneal doses of calcitriol for 12 months. Biochemical indices of mineral metabolism including serum intact PTH levels were measured monthly throughout the study, and bone biopsies were repeated at the end of treatment. Before treatment, 11 patients had osteitis fibrosa and three had mild lesions of secondary hyperparathyroidism. Histologic improvement was seen in 12 of 14 patients, and osteitis fibrosa resolved in 10 of 11 cases. Bone formation decreased in all patients during intermittent calcitriol therapy, falling from 861 +/- 380 to 150 +/- 170 microns2/mm2/day, P < 0.001. Bone formation decreased to normal in six patients, but six patients developed adynamic lesions of bone with subnormal bone formation rates. Serum PTH and alkaline phosphatase levels declined in those who developed adynamic bone, but values remained elevated in patients with normal rates of bone formation at follow-up evaluation. Neither the mean dose of calcitriol nor the average dose per kilogram body weight differed in patients with adynamic lesions. Thus, adynamic renal osteodystrophy develops in a substantial number of patients during intermittent calcitriol therapy. Although declining serum PTH and alkaline phosphatase levels suggest the development of the adynamic lesion, bone formation decreases in some patients despite persistently high serum PTH levels. Calcitriol may directly suppress osteoblastic activity in patients with secondary hyperparathyroidism when given in large doses to patients undergoing peritoneal dialysis. PMID- 7861713 TI - Hemodialysis with acetate, DL-lactate and bicarbonate: a hemodynamic and gasometric study. AB - Using invasive techniques we have studied various hemodynamic and gasometric parameters in the course of hemodialysis (HD) with different buffers in an animal model. HD sessions of 180 minutes at zero ultrafiltration were carried out on three groups of eight uremic dogs each, under anesthesia and constant mechanical ventilation. The three groups differed only in the buffer used: acetate (Group AC), equal proportions of DL-lactate and acetate (Group AC+LA), and bicarbonate (Group BC). No hemodynamic changes were seen in Group BC. In the AC and AC+LA groups we observed on minute 1 a decrease of the mean blood pressure (MBP) and of the systemic vascular resistances (SVR). These parameters returned to baseline values within the first 30 minutes in Group AC+LA. In Group AC the SVR also returned to baseline values after the minute 30, but the MBP remained below baseline throughout the study period, together with cardiac index and left ventricular stroke work index decreases. Only in Group AC did we see a flattening of the ventricular function curves. Only in this Group was there a decrease of the arterial oxygen pressure (PaO2) with an associated increase of the alveolo arterial and arterio-venous O2 differences. The O2 consumption was not modified in any of the groups. Acetate as a single buffer induces hemodynamic instability through peripheral vasodilation and reduction of myocardial contractility. The myocardial depression induced by acetate, in its turn, causes a reduction in PaO2. The mixed acetate+lactate buffer is hemodynamically better tolerated than acetate as single buffer, as it induces only vasodilation. PMID- 7861714 TI - Short-term effects of recombinant human growth hormone in CAPD patients. AB - Protein and calorie malnutrition is common in chronic dialysis patients. Several interventions have been proposed to prevent and/or to treat malnutrition. Recombinant human growth hormone (rhGH) is a drug with anabolic properties and has been used in several catabolic conditions, such as patients with severe burns as well as in pediatric patients with chronic renal failure. In this study, we evaluated the short-term effects and safety of rhGH on urea kinetics and commonly measured biochemical parameters in 10 stable adult continuous ambulatory peritoneal dialysis (CAPD) patients. The design of the study was prospective, cross-over with the patients serving as their own controls. There were three study periods: baseline (PreGH), treatment (Tx), and follow-up (PostGH). During the seven day Tx period, patients self-administered 5 mg/day s.c. of rhGH. During this time, there was a significant decrease in blood urea nitrogen (BUN) (54 +/- 15 to 40 +/- 12 mg/dl), as well as in the combined dialysate and urine urea nitrogen excretion rate (5.69 +/- 1.86 to 4.04 +/- 1.13 g/day), and protein catabolic rate (0.82 +/- 0.13 to 0.67 +/- 0.09 g/kg/day), (all P < 0.001). Serum phosphorus (4.8 +/- 1.6 to 4.4 +/- 1.8 mg/dl) and potassium (4.0 +/- 0.4 to 3.6 +/- 0.2 mEq/liter) levels also showed a small but statistically significant decrease, in conjunction with a statistically significant increase in serum creatinine levels (12.2 +/- 5.7 to 12.9 +/- 5.7 mg/dl). Dietary protein intake, determined by dietary recall, did not change during the study (66.1 +/- 20.5 vs. 75.8 +/- 22.1 grams/day).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861715 TI - Acquired essential fatty acid depletion in the remnant kidney: amelioration with U-63557A. AB - Previous studies have demonstrated an association between renal cortical fatty acid composition and experimental models of renal injury. The present study was designed to extend these observations to the remnant kidney and to investigate the hypothesis that increased endogenous turnover of arachidonic acid metabolites results in the depletion of progenitor fatty acids. Remnant kidney cortex demonstrated a relative reduction of the essential fatty acids, linoleate and arachidonate (20 +/- 7.2% and 11 +/- 0.3%, respectively), nine weeks after subtotal nephrectomy. In addition, the monounsaturated fatty acid, oleate, was increased (48 +/- 10.6%) while its saturated progenitor, stearate, was decreased (13 +/- 4.3%). Serial evaluation of dienoic prostanoids revealed a significant increase in the renal excretion of TXB2 in rats with remnant kidneys (27 +/- 3.0, 29 +/- 1.1, and 34 +/- 3.3 ng/day vs. 21 +/- 0.8, 20 +/- 1.5, and 22 +/- 3.3 ng/day in control rats, at 3, 6, and 9 weeks, respectively). Moreover, TXB2 excretion inversely correlated with dienoic progenitor fatty acids [18:2(n-6), r2 = 0.76; 20:4(n-6), r2 = 0.79], suggesting that these events are biochemically coupled. Endogenous turnover of precursor fatty acids, confirmed by an increase in renal TXB2 excretion, preceded overt depletion of essential fatty acids by several weeks. Importantly, blockade of endogenous synthesis of TXA2 with the specific TXA2 synthase antagonist, U-63557A, restored the essential fatty acid composition to normal and ameliorated progressive glomerular destruction. Moreover, the ancillary fatty acid disturbances were attenuated by administration of U-63557A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861716 TI - Epidemiology of primary glomerular diseases in a French region. Variations according to period and age. AB - Between January 1, 1976 and December 31, 1990, histological diagnosis of primary glomerular diseases (PGD) was made in 480 patients born and living at the time of diagnosis in a region of France, comprising 410,664 inhabitants, of whom 390,574 were aged from 10 to 80 years. The prevalence of PGD during a 70 year exposure to risk (10 to 80 years of age) was evaluated to 5.7 in 1000 (7.6 in 1000 males and 3.8 in 1000 females). The most common PGD was IgA nephropathy with a prevalence of 1.9 in 1000 (3.3 in 1000 males, 1 in 1000 females). The annual incidence of the disease was evaluated separately for three consecutive five-year periods: period A (1976-80), period B (1981-85), and period C (1986-90). Within each of these three periods the number of patients with PGD was 179, 170 and 131, respectively, and annual incidence was 9.3, 8.8 and 6.7 in 100,000. The incidence of IgA nephropathy remained the same throughout the three periods: 2.6, 3.1 and 2.5 in 100,000. The incidence of membranoproliferative glomerulonephritis decreased from 1981 onward (0.9, 0.5 and 0.15 in 100,000), while that of membranous nephropathy increased slightly (1.2, 1.6 and 1.7 in 100,000). Acute streptococcal glomerulonephritis virtually disappeared during periods B and C. Lipoid nephrosis was less frequent in period C and idiopathic proliferative glomerulonephritis with crescents slightly increased (0.3, 0.4 and 0.6 in 100,000). There was no significant difference between the three periods regarding the incidence of other PGD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861717 TI - Greater inhibition of in vitro bone mineralization with metabolic than respiratory acidosis. AB - At a similar decrement in pH, acidosis produced by lowering the concentration of medium bicarbonate (metabolic acidosis) induces greater net calcium efflux from cultured neonatal mouse calvariae than acidosis produced by increasing the partial pressure of carbon dioxide (respiratory acidosis). This differential effect is due, at least in part, to enhanced cell-mediated bone mineral resorption during metabolic acidosis. To determine the effect of acidosis on osteoblastic bone formation we utilized primary cultures of neonatal mouse calvarial cells which produce calcified nodules in culture. Cells were plated at 4.5 x 10(4) cells/35 mm dish and incubated until confluent (day 9). Nodule formation was then induced by addition of beta-glycerophosphate and ascorbic acid and the cultures were randomly divided and then cultured in control (Ctl, N = 18) medium or in medium simulating metabolic (Met, N = 17) or respiratory (Resp, N = 19) acidosis. Medium was changed and calcium (Ca) measured every 48 hours until day 23. The mean initial medium pH of all Resp cultures (7.186 +/- 0.002) was lower than Met (7.243 +/- 0.006, P < 0.01), which was lower than Ctl (7.502 +/- 0.002, p < 0.01), yet the number of discrete nodules formed in Met (22 +/- 4 nodules/cm2) was lower than Resp (43 +2- 7, P < 0.01), and both were lower than Ctl (88 +/- 6, P < 0.01 vs. both Met and Resp).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861718 TI - Expression and distribution of epidermal growth factor in acute and chronic renal allograft rejection. AB - Epidermal growth factor (EGF) is a fibrogenic cytokine with a possible role in chronic damage. EGF is also involved in tubular regenerative response to injury. This study investigates the expression and distribution of EGF in a rat model of renal allograft rejection. EGF was localised in control kidneys to distal convoluted tubules (DCT) and thick ascending loop of Henle (TAL). Five days post transplantation EGF was diffusely distributed. In chronic rejection at one, three and six months, damaged areas of allografts demonstrated faint diffuse EGF staining, while well-preserved areas exhibited the normal distribution pattern. PreproEGF mRNA was significantly reduced (P < 0.01) in acute rejection and in chronic rejection at three months to 28% and 51% of normal, respectively. At six months values ranged from 16% to 166% of normal kidneys, and were inversely correlated with tubular damage (P < 0.01). PreproEGF mRNA was localized to DCT and TAL in controls and in well preserved areas of the tissue in chronic rejection. Thus, EGF would not appear to contribute to the development of injury in chronic renal rejection. It may instead exert a protective effect on tubular structures. PMID- 7861719 TI - A prospective study of renal structure and function in psoriasis patients treated with cyclosporin. AB - The impact of long-term cyclosporin therapy on kidney structure and function was evaluated in psoriasis patients with normal baseline renal function. Patients received cyclosporin at an average dose 3.9 mg/kg/day for up to three years and underwent serial kidney biopsies and measurements of iothalamate clearance and serum creatinine concentration. Kidney biopsy specimens (assessed on a scale of 0 to 4 where 0 = normal and 4 = severe) from 19 cyclosporin-treated patients as compared to 38 age-matched transplant donors showed increased interstitial fibrosis (1.9 +/- 0.2 vs. 0.3 +/- 0.1, P < 0.0001) and tubular atrophy (1.6 +/- 0.2 vs. 0.3 +/- 0.1, P < 0.0001) at one year. Eleven patients had a second biopsy after an additional two years of cyclosporin treatment demonstrating additional interstitial fibrosis (1.8 +/- 0.2 to 2.4 +/- 0.3, P = 0.002) and tubular atrophy (1.4 +/- 0.2 to 1.9 +/- 0.2, P = 0.053), and the onset of cyclosporin-associated arteriolopathy (0 to 0.5 +/- 0.2, P = 0.02). Quantitative digital morphometric analysis of trichrome-stained specimens also showed increased interstitial fibrosis (22.5 +/- 1.5 to 32.0 +/- 2.0% of interstitial area, P = 0.0008). Iothalamate clearance declined at an average rate of -3.1 ml/min/1.73 m2 per year (95% CI -5.8, -0.3) during the period of cyclosporin treatment. The slope of reciprocal serum creatinine declined by -0.06 dl/mg per year (95% CI -0.08, 0.04). Chronic cyclosporin treatment of otherwise healthy psoriasis patients is associated with progressive renal structural injury and reduced glomerular filtration rate. PMID- 7861720 TI - The many masks of focal segmental glomerulosclerosis. PMID- 7861721 TI - Hereditary and acquired cystic disease of the kidney. PMID- 7861722 TI - Monoclonal immunoglobulin deposition disease (Randall type). Relationship with structural abnormalities of immunoglobulin chains. PMID- 7861723 TI - Developmental changes in angiotensin II receptor subtypes and AT1 receptor mRNA in rat kidney. AB - The changes in angiotensin II receptor subtypes, type 1 (AT1) and type 2 (AT2) binding, and AT1 mRNA levels during development were studied in the rat kidney using autoradiographic and in situ hybridization techniques. Autoradiographic analysis of 125I-[Sar1,Ile8]Ang II binding to slide-mounted kidney sections from 2 and 5 day-old rats discerned AT2 binding sites associated with advancing tubules and ampullae of the ureteric bud, and in the metanephric mass in the nephrogenic zone of the cortex. AT1 binding was present in the metanephric mass and immature glomeruli on days 2, 5 and 7 after birth. Differentiating and mature kidneys of 14-day, 21-day and 14-week old adult rats had solely AT1 receptor binding over glomeruli in renal cortex and in the inner stripe of the outer medulla. AT1 mRNA was expressed discretely as early as 2 days of age in the immature glomeruli and in a diffuse radiating pattern in the renal cortex. In the medulla, AT1 receptor mRNA expression appeared discretely on day 7 and reached peak levels on day 21 in the inner stripe of the outer medulla. The data indicate that AT1 receptor mRNA is developmentally regulated in rat kidney and its expression in the cortex precedes that of AT1 receptor ligand binding. The temporal pattern of expression of binding for both receptor subtypes suggests that while AT2 receptors may be involved in cell proliferation and early differentiation of the nephron, AT1 receptors have a dual role, early in nephron differentiation and later in development in renal function. PMID- 7861724 TI - The effect of acute angiotensin II blockade on renal function in rats with reduced renal mass. AB - The effect of acute Ang II blockade on renal function in rats with reduced nephron number was assessed in micropuncture studies. The Ang II receptor blocker, losartan, was administered at a dose of 10 mg i.v. at two intervals following five-sixths renal ablation. At eight weeks following ablation, Ang II blockade (Ang IIX) increased sodium excretion [UNa V, Ang IIX 2.2 +/- 0.4 microEq/min; time control (TC) 1.0 +/- 0.3 microEq/min; P < 0.05] but did not reduce mean arterial pressure (AP, Ang IIX 142 +/- 6 mm Hg; TC 151 +/- 6 mmHg), glomerular transcapillary pressure (delta P, Ang IIX 50 +/- 1 mm Hg; TC 50 +/- 1 mm Hg), or urine albumin excretion (UAlb V: Ang IIX 149 +/- 18 micrograms/min; TC 168 +/- 20 micrograms/min). Similarly, at two weeks following ablation, Ang II blockade increased UNa V (Ang IIX 2.8 +/- 0.4 microEq/min; TC 0.5 +/- 0.2 microEq/min; P < 0.05) without reducing AP (Ang IIX 132 +/- 6 mm Hg; TC 140 +/- 7 mm Hg), delta P (Ang IIX 50 +/- 3 mm Hg; TC 48 +/- 2 mm Hg), or UAlb V (Ang IIX 32 +/- 3 micrograms/min; TC 36 +/- 10 micrograms/min). These findings indicate that within the remant kidney, Ang II promotes sodium retention but does not have an acutely reversible effect on glomerular pressure or permselectivity. PMID- 7861725 TI - Human peritoneal mesothelial cells synthesize IL-1 alpha and beta. AB - We studied the ability of human peritoneal mesothelial cells (HPMC) to produce the major pro-inflammatory cytokines interleukin-1 alpha (IL-1 alpha) and -beta when stimulated by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) or IL-1 alpha, or combinations of these three factors. Biological activity of IL-1 was measured by bioassay, and levels of IL-1 alpha and beta were determined using specific radioimmunoassays. We found that HPMC are capable of secreting IL-1 alpha and -beta in response to stimulation by these substances, but stimulation with a combination of LPS + TNF alpha, LPS + IL-1 alpha, or TNF alpha + IL-1 alpha, had a marked synergistic effect on cytokine production. A combination of all three substances together had a significantly enhanced synergistic effect. Using reverse transcription PCR, we found a peak in IL-1 alpha and beta mRNA levels three hours after stimulation. We found that LPS, TNF alpha and IL-1 alpha alone, or in combination, caused an increase in IL-1 alpha and -beta mRNA levels. Cycloheximide and actinomycin D blocked the production of IL-1 alpha and -beta protein, showing that de novo production of IL-1 or synthesis of mRNA stabilizing proteins are needed after stimulation. We thus conclude that HPMC play an important role in the amplification of the initial peritoneal inflammatory response which originates in the peritoneal macrophages, and these findings are of importance in understanding the peritoneal response to infection in continuous ambulatory peritoneal dialysis (CAPD) patients. PMID- 7861726 TI - [Nursing standards: nursing measures for the support of respiration and for the prevention of pneumonia]. PMID- 7861728 TI - [Cochlear implantation in children]. PMID- 7861727 TI - [Sexuality and care]. PMID- 7861729 TI - [Backache--back school; back school programs in nursing]. PMID- 7861730 TI - [Disorders of the water and electrolyte metabolism in intensive care patients]. PMID- 7861731 TI - [Alginates--undervalued aids in severely discharging wounds]. PMID- 7861732 TI - [Electronic video-endoscopy]. PMID- 7861734 TI - [Microsystem techniques in medicine. Keyhole surgery]. PMID- 7861733 TI - [20 years of X-ray computerized tomography--new technology offers more diagnosis and helps to save money]. PMID- 7861735 TI - [New measuring systems for the diagnosis of vascular diseases: modern technique detects calcium deposits]. PMID- 7861736 TI - [Small man and the huge universe]. PMID- 7861737 TI - [Explantation and instrumentation--exemplified by kidney explantation]. PMID- 7861738 TI - [Preserved and prepared bones]. PMID- 7861739 TI - [Minimally invasive surgery--a challenge for the nursing personnel]. PMID- 7861740 TI - [What has to be taken into consideration in the handling and maintenance of apparatus and instruments for minimally invasive surgery?]. PMID- 7861741 TI - [The operating room nurse and the surgeon--reality and dream]. PMID- 7861742 TI - [The surgeon and his nurse--dream and reality]. PMID- 7861743 TI - [Naturopathic measures in gynecology and their possible uses in nursing]. PMID- 7861744 TI - [The central problem for the future is not nursing insurance but the missing humanity]. PMID- 7861745 TI - [Hygienic aspects in the care of home care patients with AIDS, chronic diseases and mental retardation]. PMID- 7861746 TI - [Let us work--without discussion]. PMID- 7861747 TI - [Breaking in new coworkers in surgery]. PMID- 7861748 TI - Analysis of the neurotoxic plasticizer n-butylbenzenesulfonamide by gas chromatography combined with accurate mass selected ion monitoring. AB - The plasticizer, n-butylbenzenesulfonamide (NBBS), is reported to be neurotoxic when inoculated intracisternally or intraperitoneally into rabbits. Because NBBS is commonly used in the production of polyamide (nylon) plastics and is soluble in water, the disposal of NBBS-containing plastics in landfill sites could result in NBBS appearing in the leachate. Further, NBBS could also be leached from packaging into their contents. To allow us to examine the risks posed by NBBS in the environment, we have developed a quantitative assay for this compound. The assay employs a one-step extraction into dichloromethane followed by gas chromatography with accurate mass selected ion recording. The assay incorporates [13C6]NBBS as an internal standard to allow precise quantitation, and four separate ion chromatograms are recorded. NBBS was found in some Australian domestic solidwaste landfill leachate (from less than 0.3 to 94.6 ng/mL), but ground water in the vicinity of a landfill had only trace quantities of NBBS. NBBS was also quantitated in some bottled and cask wines, and levels varied from not detected to 2.17 ng/mL (n = 14). Additional studies are required to assess the public health risks associated with the use of NBBS as a plasticizer. PMID- 7861749 TI - GC-MS confirmation of urinary benzodiazepine metabolites. AB - A confirmatory method using gas chromatography-mass spectrometry (GC-MS) is described for benzodiazepine metabolites commonly encountered in urine. The targeted drugs are diazepam, nordiazepam, temazepam, oxazepam, lorazepam, alpha hydroxyalprazolam, alpha-hydroxytriazolam, 2-hydroxyethyl-flurazepam, N-desalkyl 3-hydroxyflurazepam, and N-desalkylflurazepam. After enzymatic hydrolysis, the free benzodiazepines are recovered from the urine by liquid-liquid extraction. The organic solvent is evaporated to dryness. The residue is subjected to sequential derivatization involving propylation of the secondary amine in the lactam ring followed by propionylation of hydroxyl groups. The derivatives are separated on a methyl silicone capillary column and then identified and quantitated by full-scan GC-MS. Characteristic ion clusters are selected for quantitation. Four internal standards are used: oxazepam-d5, lorazepam-d4, alpha hydroxyalprazolam-d5, and alpha-hydroxytriazolam-d4. PMID- 7861750 TI - Optimal enzymatic hydrolysis of urinary benzodiazepine conjugates. AB - Conditions for the enzymatic hydrolysis of benzodiazepine conjugates were systematically examined. Optimal recovery of the free drugs occurs when 1 mL of urine buffered to pH 4.5 is incubated with 5000 U of Helix pomatia beta glucuronidase at 56 degrees C for 2 h. Urine specimens containing conjugates of temazepam, oxazepam, lorazepam, alpha-hydroxyalprazolam, 2 hydroxyethylflurazepam, and N-desalkyl-3-hydroxyflurazepam as targeted benzodiazepines were used. The freed drugs were quantitated by gas chromatography mass spectrometry. PMID- 7861751 TI - Benzodiazepine screening using EMIT II and TDx: urine hydrolysis pretreatment required. AB - Urine specimens were collected from individuals prescribed oral doses of the following benzodiazepine tablets: diazepam, oxazepam, temazepam, lorazepam, alprazolam, flurazepam, and chlordiazepoxide. An aliquot was hydrolyzed using Helix pomatia beta-glucuronidase. Both the hydrolyzed and unhydrolyzed urine pairs were subjected to EMIT II and TDx immunoassay screening tests and to gas chromatographic-mass spectrometric quantitation. Hydrolysis is required to ensure adequate detection of oxazepam, temazepam, and lorazepam with either screening method. A 100-ng/mL cutoff is required when screening for lorazepam, following therapeutic doses. The EMIT II is more sensitive than the TDx as a screening test for benzodiazepines. PMID- 7861752 TI - Stability of drugs of abuse in urine samples stored at -20 degrees C. AB - Isolated studies of the stability of individual drugs of abuse have been reported. However, few have evaluated stability in frozen urine samples stored for 12 months. We have determined the stability of 11-nor-9-carboxy-delta 9 tetrahydrocannabinol (9-COOH-THC), amphetamine, methamphetamine, morphine, codeine, cocaine, benzoylecgonine, and phencyclidine in 236 physiological urine samples. Following the initial quantitative analysis, the samples were stored at 20 degrees C for 12 months and then reanalyzed. All drug concentrations were determined by gas chromatographic-mass spectrometric methods with cutoff concentrations of 5 ng/mL for 9-COOH-THC and phencyclidine and 100 ng/mL for each of the other drugs. The average change in the concentrations of these drugs following this long-term storage was not extensive except for an average change of -37% in cocaine concentrations. PMID- 7861753 TI - Analysis of polychlorinated dibenzofurans (PCDFs) in fly ash from a waste incineration plant. AB - In this study, a method for the congener-specific analysis of polychlorinated dibenzofurans (PCDFs) in fly ash from a waste incineration plant is described. This method involves extraction, column chromatography, and gas chromatographic mass spectrometric techniques. Representative fly ash samples are obtained from the waste incinerator. The purpose of this research is to briefly present the findings as they relate to PCDFs. Analyses indicate that PCDFs are consistently found in the municipal incinerator. PMID- 7861754 TI - Impact of hot and humid tropical conditions on Toxi-Lab thin-layer chromatographic systems for the screening of basic and neutral drugs. AB - Because thin-layer chromatography can be affected by climatic conditions, we investigated the impact of high temperatures (33-38 degrees C) and high relative humidities (80-100%) on the applicability of Toxi-Lab thin-layer chromatographic systems for the screening of basic and neutral drugs during a 6-month climatological cycle in Jakarta, Indonesia that can be characterized as hot and humid. In general, the Rf values as observed on the plate showed substantial deviations from those in the literature obtained in moderate climates. Most substances gave higher Rf values, and the deviations (sometimes amounting to 20 Rf units) increased with increasing humidities. However, when the observed Rf values were corrected by means of a reference mixture of standard drugs that was run on each plate, much better accuracy and reproducibility were obtained. Thus, these corrected Rcf values were compatible with the existing databases developed in temperate climates. These results are in line with earlier studies carried out under hot and dry conditions. In the earlier studies, the observed Rf values tended to be lower than those present in other databases, but here too, the Rf correction procedure corrected this phenomenon. PMID- 7861755 TI - Application of the novel immunoassay TRIAGE to a rapid detection of antemortem drug abuse. AB - The applicability of the immunoassay TRIAGE (E. Merck, Darmstadt, Germany) as a simple and rapid assay for antemortem drug abuse was tested on 100 urine samples from forensic autopsies. The samples were also analyzed by fluorescence polarization immunoassay and by chromatographic methods. The confirmation rate of the TRIAGE results by chromatographic analysis was 92% for benzodiazepines, 95% for cannabinoids, 96% for cocaine, 100% for opiates and barbiturates, and 82% for amphetamines. Because the urine samples were taken from corpses, the latter finding can be explained by false-positive amphetamine results due to cross reactivity of the antibodies used in current immunoassay technologies with phenylalkylamines, which are generated in postmortem decomposition processes. In fact, tyramine, a typical product of putrefaction, was identified by gas chromatography-mass spectrometry in 11 samples of false-positive amphetamine determinations. TRIAGE produces positive amphetamine results for samples containing tyramine in concentrations of more than 5 mg/L. The detection limit of the TRIAGE assay for 7-aminoflunitrazepam, the major urinary metabolite of flunitrazepam, is within the range of 0.5-1 mg/L. PMID- 7861756 TI - Measurement of lead in blood by graphite furnace atomic absorption spectrometry. AB - A simple method of deproteinizing whole blood with an 0.8M (5%, v/v) nitric acid solution containing Triton X-100 (0.1%, v/v) is described. The resulting supernatant is used for the measurement of lead by Zeeman graphite furnace atomic absorption spectrometry using calibration with aqueous standards. Recoveries ranged from 97.7-105.6% when an aqueous lead solution was added to a deproteinized sample supernatant and from 98.5-104.5% when whole blood control material was added to a whole blood sample. At a blood lead concentration of 11.2 micrograms/dL, the within- and between-run coefficients of variation were both approximately 5%. Comparison of the proposed method versus one using a recommended matrix modifier gave a regression equation of Y(proposed) = 0.99x(matrix modifier)-0.36, with a correlation coefficient of r = 0.994 (n = 54). PMID- 7861757 TI - Direct determination of benzoylecgonine in serum by EMIT d.a.u. cocaine metabolite immunoassay. AB - An EMIT d.a.u. immunoassay for urine testing was applied on the Syva ETS Plus analyzer for the detection of the cocaine metabolite, benzoylecgonine (BE), in human serum. Serum was analyzed without prior extraction, concentration, or matrix modification. Calibrators and serum controls were prepared from EMIT d.a.u. calibrators that were reconstituted and diluted with EMIT Tox serum calibrator. The assay cutoff concentration for BE was 50 ng/mL. The within-run and between-run precisions of the assay were both less than 5%. Analysis of 162 patient serums yielded 43 BE positive results. All EMIT positive serum BE results were confirmed by gas chromatography-mass spectrometry. All patients with positive BE serums also had BE positive urine samples. Serum bilirubin and triglycerides as high as 38 mg/dL and 319 mg/dL, respectively, did not interfere with the assay. Modification of the EMIT urine assay allowed for a simple, rapid, and reliable method for the detection of BE in serum. PMID- 7861758 TI - Unexpected volatility of barbiturate derivatives: an extractive alkylation procedure for barbiturates and benzoylecgonine. PMID- 7861759 TI - Inaccuracies in a procedure for cyanide determination. PMID- 7861760 TI - Discordant benzodiazepine results by immunoassay. PMID- 7861761 TI - Effects of subcutaneous expansion on the mechanical properties of porcine skin. AB - The purpose of this study was to determine the effects of conventional and intraoperative tissue expansion on the biomechanical properties of skin. Two 200 cc silicone tissue expanders were inserted subcutaneously in each of six young pigs. One expander was inflated conventionally (4 weeks) and the other intraoperatively (three times within 1 hr). A skin specimen was excised from each expansion site and each contralateral control site and tested under tension to failure. The sites were closed and allowed to heal for 4 weeks at which time another biopsy specimen was taken from each site. Histological observations and biochemical analyses were conducted. Also, tangent modulus and ultimate stress were determined from the mechanical response of each specimen. Results indicated an initial decrease in stiffness and ultimate strength for conventionally expanded skin. The mechanism for this decrease could not be explained via our current biochemical and histological techniques. Mechanical properties for conventionally expanded skin, after healing, were not significantly different than controls. The mechanical properties for intraoperatively expanded skin were not significantly altered with respect to controls, either at initial expansion or after 4 weeks of healing. The tissue "generated" as a result of intraoperative expansion in the porcine model is likely tissue recruited from the surrounding skin. PMID- 7861762 TI - Tumor necrosis factor-alpha and interleukin-6 selectively regulate neutrophil function in vitro. AB - The neutrophil is an important effector cell of the host response to sepsis. Tumor necrosis factor-alpha (TNF-alpha), a cytokine mediator of the septic response, is rapidly released following endotoxemia or gram-negative bacteremia. Interleukin-6 (IL-6) is another cytokine mediator of the host response to sepsis whose role is less well understood than that of TNF-alpha. It is known to be elevated in gram-negative sepsis, where peak levels have been correlated with mortality. This study examined the effect of IL-6 alone and in combination with TNF-alpha on three neutrophil functions--CD18 adhesion receptor expression, phagocytosis, and superoxide anion generation. Neutrophils from human volunteers were incubated with amounts of IL-6 ranging from 10 to 1000 ng/ml. At a concentration of 1000 ng/ml, IL-6 increased neutrophil phagocytosis of opsonized bacteria (826 +/- 255 x 10(3) MESF vs 552 +/- 103 MESF, P < 0.05) and also increased neutrophil superoxide anion generation (18.41 +/- 1.86 vs 12.6 nmol O2 /10(6) PMN/10 min, P < 0.05). Lesser amounts of IL-6 had no effect on phagocytosis or superoxide generation. IL-6 did not increase neutrophil CD18 adhesion receptor expression. Combining IL-6 with TNF-alpha at doses of 100 ng/ml and 100 U/ml, respectively, neutrophil phagocytosis (221 +/- 455 MESF vs 552 +/- 103 MESF) and superoxide generation (23.18 +/- 1.86 vs 12.6 nmol O2-/10(6) PMN/10 min) were significantly (P < 0.05) increased above control by an amount similar to that seen with 1000 U/ml TNF-alpha alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861763 TI - Significance of altered fluidity of plasma membranes of the liver and kidney in rats with sepsis. AB - The present study was conducted to investigate changes in plasma membrane fluidity of the liver and kidney in sepsis, which is the main cause of multiple organ failure. Male Wistar rats weighing 200-250 g were used in all experiments. Sepsis was induced by cecal ligation and puncture. As a control, a sham operation was performed. The time course of plasma membrane fluidity of the liver and the renal cortex in septicemic rats or in controls was studied. To evaluate the fluidity, fluorescence polarization was measured using 1,6-diphenyl-1,3,5 hexatriene. The fluorescence polarization values of liver plasma membranes increased after cecal ligation and puncture: 0.183 +/- 0.004 (mean +/- SEM), 0.194 +/- 0.008, 0.206 +/- 0.003, and 0.210 +/- 0.002 at 0, 24, 48, and 72 hr, respectively. Corresponding values for membranes of the renal cortex increased in a similar fashion. To determine whether factors involved in cell membrane damage exist in blood, the direct effects of lipopolysaccharide (LPS), platelet activating factor (PAF), and serum from normal rats or from septicemic rats on membrane fluidity were studied. The fluorescence polarization of plasma membranes of the liver or renal cortex to which septicemic rat serum was added was higher than that of plasma membranes to which normal rat serum was added. The fluorescence polarization of liver plasma membranes was increased by LPS, but that of plasma membranes of the renal cortex was slightly decreased. In addition, the fluorescence polarization of liver plasma membranes was increased by PAF, but that of plasma membranes of the renal cortex was decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861764 TI - Effect of burn injury on intestinal Na+/H+ exchangers. AB - The Na+/H+ exchangers at the brush border membrane (BBM) and the basolateral membrane (BLM) are each distinct with different kinetic and pharmacologic characteristics. At the BBM, Na+/H+ exchange provides an acid microenvironment necessary for nutrient transport. At the BLM, the Na+/H+ exchanger regulates intracellular pH and cell volume which affect cell growth and repair. This study was designed to determine the effect of burn injury on Na+/H+ exchange at the BBM and BLM of the rat enterocyte. Adolescent Sprague-Dawley rats were divided into control (n = 6) and 20% scald burn groups (n = 6). Using differential centrifugation and percoll density gradient techniques, BBM and BLM vesicles were prepared from the jejunum. 22Na+ uptake was measured using a rapid filtration technique. Initial rate uptake studies showed that the slope of Na+ uptake in BBM (y = 0.06x + 0.12, r2 = 0.99) and BLM (y = 0.075x + 0.1, r2 = 0.99) of the control group was higher (P < 0.05) than that in the burn group (y = 0.0345x + 0.06, r2 = 0.98 and y = 0.056x + 0.01, r2 = 0.99). To determine whether the changes in transport are related to the feeding pattern in burn rats, similar experiments were done in pair-fed animals. The initial rate uptake studies of BBM showed a similarily greater slope of Na+ uptake in pair-fed control animals compared to the burn group (y = 0.043x + 0.06, r2 = 0.99 and y = 0.062x + 0.008, r2 = 0.98; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861765 TI - Norepinephrine infusion following cardiopulmonary bypass: effect of infusion site. AB - The placement of left atrial catheters following cardiopulmonary bypass (CPB) allows accurate monitoring of left ventricular filling pressures, as well as access for the infusion of vasoactive drugs. While the left atrial administration of norepinephrine (NE) is thought to provide higher systemic arterial NE levels while minimizing any pulmonary vasoconstriction, no study critically compares central venous and left atrial NE infusion following cardiopulmonary bypass. A canine model was used to compare central venous and left atrial NE infusion at three dosages (0.2, 0.4, and 0.6 microgram/kg/min) both prior to CPB and following 2 hr of hypothermic CPB at 27 degrees C. Prior to CPB, there was no difference in the hemodynamic efficacy of central venous and left atrial NE infusion at any dosage. The pulmonary circulation metabolized 16-29% of circulating NE. Only at the 0.2 microgram/kg/min dose was there a difference in the arterial NE level between central venous (3474 +/- 486 pg/ml) and left atrial (5504 +/- 751 pg/ml, P = 0.019) NE administration. Above this dose, no difference in the arterial NE level was identified. Following 2 hr of CPB, the pulmonary endothelium metabolized a significantly higher percentage of circulating NE (35 42%). Despite this increased extent of pulmonary metabolism, there was no difference in the hemodynamic efficacy or the resulting arterial NE level of central venous and left atrial NE infusion at a given dose. In conclusion, the results demonstrate: (1) increased pulmonary NE uptake following CPB, and (2) no difference in hemodynamic efficacy between central venous and left atrial NE infusion over a wide range of three doses in a model with normal lungs. PMID- 7861766 TI - Cholecystokinin effect on human lymphocyte ionized calcium and mitogenesis. AB - Cholecystokinin (CCK) is a peptide present in large amounts in gut, brain, and neurons innervating lymphatic tissues. Plasma CCK levels increase in enterally alimented patients. Enteral alimentation is also associated with enhanced immune function. The effects of CCK and a CCK antagonist were studied on human peripheral blood mononuclear cells (H-PBMC), lymphocyte intracellular ionized calcium ([Ca2+]i), and lymphocyte mitogenesis. CCK receptors transduce their signal via the release of [Ca2+]i. CCK octapeptide caused a specific increase in [Ca2+]i measured by Fura-2 fluorometry in H-PBMC and human T helper lymphocytes. Neither gastrin-17 nor pentagastrin produced a signal. While the highly specific CCK antagonist MK329 blocked the CCK [Ca2+]i signal, it had no effect on the PHA mediated signal. At high dosages (10(-7)-10(-8) M), CCK was a comitogen with "complete" lymphocyte mitogens such as anti-CD3 monoclonal antibody (mAb) or low dose PHA, but not for "partial" mitogens such as phorbol esters. CCK comitogenic effect occurred even in the presence of cyclosporine. CCK radioimmunoassay demonstrated that H-PBMC contained CCK and that anti-CD3 mAb- or PHA-mediated H PBMC mitogenesis caused release of CCK. MK329 blocked PHA and anti-CD3 mAb mitogenesis and CCK comitogenic effects. We conclude that CCK octapeptide may be a coregulator of lymphocyte Ca2+ activation signals. The immunologically beneficial effect of enteral nutrition may, in part, be mediated by increased levels of CCK. PMID- 7861767 TI - Glutamine reduces bacterial translocation after small bowel transplantation in cyclosporine-treated rats. AB - Bacterial translocation (BT) of enteric organisms is a major cause of sepsis in patients undergoing small bowel transplantation (SBT). Cyclosporine (CsA) may be toxic to intestinal epithelium and increase the risk of BT. Glutamine (Gln) is the preferred enterocyte fuel and maintains graft epithelial integrity in experimental SBT. This study determined the effects of CsA on mucosal structure and function of transplanted intestinal isograft and examined whether Gln enriched diet reversed CsA-induced intestinal toxicity. Thirty-three adult Lewis rats underwent resection of the distal 60% of small bowel and received an orthotopic jejunal isograft. Rats received either elemental diet with 2% Gln or the same diet with balanced nonessential amino acids (non-Gln) by gastrostomy for 10 days. CsA (15 mg/kg, im) or olive oil was injected daily. Rats were assigned to four groups: non-Gln with vehicle, non-Gln with CsA, Gln with vehicle, and Gln with CsA. Mucosal villous height, surface area, crypt depth, 14C glucose absorption, BT to mesenteric lymph nodes (MLN), and body weight change were evaluated. The non-Gln with CsA group had the highest incidence of BT (P < 0.001). Gln groups had significantly decreased BT (P < 0.01) and increased crypt depth and villous surface area (P < 0.01) when compared to non-Gln groups. Body weight significantly decreased in CsA groups when compared to non-CsA groups (P < 0.01). These results indicate at CsA significantly decreased body weight and increased BT without decreasing mucosal structure and glucose absorption of intestinal isografts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861768 TI - Clonal interactions in a human squamous cell carcinoma. AB - F.2a and B.2, cell clones of the human squamous cell carcinoma SCC-12, were examined to characterize their interactions through the expression of growth factors. F.2a was nontumorigenic yet B.2 was fully tumorigenic when injected into the flanks of athymic nude mice. Combination injections of F.2a and a subtumorigenic level of B.2 produced tumors. F.2a and B.2 overexpressed the 4.8 kb transcript for transforming growth factor-alpha (TGF-alpha) as well as the 10.5- and 5.8- kb transcripts for the epidermal growth factor receptor. Neither clone expressed the transcript for epidermal growth factor, while both expressed transcripts for insulin-like growth factor-I (IGF-I) of 8.15, 4.9, and 1.6 kb and transcripts for its receptor of 8.5 and 6.5 kb. Conditioned medium (CM) from either clone stimulated the growth of itself and the other clone in tissue culture. Both clones produced intracellular TGF-alpha detectable by immunohistochemical staining, but not detectable in CM by enzyme-linked immunosorption assay. IGF-I was detected at low levels in CM by radioimmunoassay. Neutralizing antibodies to TGF-alpha but not IGF-I partially inhibit the growth of both clones in tissue culture. These results suggest that (1) TGF-alpha is active in autocrine signaling (2) IGF-I is not directly stimulatory, and (3) additional factors, as yet unidentified, are present in CM and enhance tumor growth. It is concluded that human squamous cell carcinoma SCC-12 is composed of tumorigenic and nontumorigenic clones which interact to enhance growth. PMID- 7861769 TI - Primary and reversible injury of H(+)-ATPase in warm ischemia and reperfusion of rat liver in relation to intramitochondrial adenine nucleotide. AB - The injury and recovery processes of complex reactions of liver mitochondrial ATP synthesis during warm ischemia and after reflow were studied separately in terms of the changes in oxidation (electron transfer system) and phosphorylation (H(+) ATPase). Oxidative activity decreased significantly from the control value of 40 +/- 0.9 (mean +/- SEM, n = 5) to 31.5 +/- 1.13 (nanoatoms oxygen consumed/min/mg protein) after 40 min of warm ischemia, while phosphorylative activity decreased significantly from the control value of 1.06 +/- 0.12 to 0.42 +/- 0.03 (mumole ATP hydrolyzed/min/mg protein) after 20 min of warm ischemia. During 120 min of reflow after 20 min of warm ischemia, the decreased phosphorylation activity recovered to 0.52 +/- 0.01 concomitant with a recovery of intramitochondrial total adenine nucleotide and an increase in the ATP/ADP ratio, while oxidative activity decreased further to 23.9 +/- 0.81. These results indicate that H(+) ATPase is more vulnerable to warm ischemia than the electron transfer system, but that it is restored concomitant with the recovery of intramitochondrial adenine nucleotide content. PMID- 7861770 TI - Hyperacute rejection of liver allografts in sensitized rats: role of nonparenchymal liver cells. AB - Reasons why liver allografts are more resistant to antibody mediated rejection than other organ allografts are not fully understood. In order to define the role of nonparenchymal liver cells, we have compared the fate of liver allografts in two combinations of sensitized inbred rats. In the DA into LEW combination, hyperacute rejection of liver allografts was observed (mean survival time of liver grafted rats was 5.2 +/- 0.6 hr). A sharp decrease of the level of cytotoxic antibodies was observed after transplantation associated with deposits of IgG, IgM, C3, and fibrinogen on sinusoidal cells. Macroscopic and histological aspects of liver allografts were suggestive of an antibody-mediated rejection with congestion and portal hemorrhage. On the contrary, in the LEW into BN combination, survival time was significantly longer (259.2 +/- 25.2 hr), whereas histological studies demonstrated signs of cellular rejection. A decrease in the level of cytotoxic antibodies was present and deposits of IgG, IgM, C3, and fibrinogen were more significant. After blockade of the Kupffer cells of the LEW transplanted liver, survival time of the BN rats was significantly reduced (38.8 +/- 8.0 hr). Macroscopic and histological aspects of the grafts were suggestive of antibody-mediated rejection and deposits of IgG, IgM, and C3 were reduced. The results suggest the hypothesis that resistance of liver allografts to antibody mediated rejection is probably due to the ability of nonparenchymal liver cells to absorb preformed cytotoxic antibodies and complement. PMID- 7861771 TI - Comparison of skeletal muscle laser Doppler flowmetry to changes in central hemodynamics in detecting the physiological response to moderate hemorrhage. AB - Previous studies have demonstrated that laser Doppler (LD) flowmetry is a useful technique for following changes in blood flow in a tissue bed, but the potential role of LD flowmetry in management of the critically ill patient is unclear. This study sought to establish the sensitivity of LD flowmetry compared to changes in centrally measured hemodynamic parameters in response to a mild hemorrhagic episode. In order to establish the correlation between LD flow and actual blood flow, livers from Sprague-Dawley rats were isolated and perfused via the portal vein with citrate anti-coagulated rat blood. Changes in LD flow were recorded while changing blood flow via the perfusion pump. There was a strong correlation between pump flow and LD flow (for N = 5 livers, r > 0.9; P < 0.05). This relationship was stable at hematocrits > 20. The second part of this study tested the sensitivity of LD flowmetry in anesthesized baboons. An LD probe was placed on the surface of the gracilis muscle of the adult male baboons. LD flow and hemodynamic parameters were measured following two episodes of bleeding and reinfusing 250 cc of blood. During the first bleed there were significant changes in heart rate (97 + 8 to 159 + 12), mean arterial pressure (125 + 6 to 105 + 9), and LD flow (20.6 + 4.6 to 11.9 + 3.6); these parameters returned to normal after reinfusion of blood. During the second bleed, the only parameters that showed significant changes were heart rate (118 + 5 to 135 + 12) and LD flow (17.5 + 8 to 10.7 + 3.4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861772 TI - Small bowel tissue high-energy phosphate regeneration after 7 hr of cold ischemic storage: comparison of University of Wisconsin and Eurocollins solutions. AB - As adenine nucleotide content has been shown to correlate with post-transplant function of livers and hearts, it was the aim of our study to investigate the regeneration of rat small bowel tissue high-energy phosphates after 7 hr of cold storage followed by incubation of everted small bowel sacs in normothermic oxygenated KHB for 1 hr. We compared the University of Wisconsin (UW) and the Eurocollins (EC) solutions. Krebs-Henseleit-bicarbonate buffer (KHB) was used to point out the effect of simple cold ischemic storage. After 7 hr of cold storage only small bowel stored in UW and EC solutions retained the capacity for almost total regeneration of ATP necessary for optimal posttransplant function, whereas in the KHB group we found only minimal regeneration. A similar pattern was found for the energy charge. These data support the superiority of UW and EC solutions over simple cold storage in KHB for preservation of small bowel. PMID- 7861773 TI - Complexes of a modified low-molecular-weight heparin with protamine are predominantly cleared by a macrophage scavenger receptor-mediated process in rats. AB - Neutralization of heparin with its antidote protamine is associated with side effects such as pulmonary hypertension. The pharmacodynamic effects of protamine treatment are well documented. However, little is known about metabolic fate of heparin-protamine complexes. Twenty Wistar rats received a 131I-labeled low molecular-weight heparin tracer intravenously. Four groups of animals were formed: a control group receiving the tracer, a second group receiving protamine after tracer application, a third group receiving maleylated bovine serum albumin (mal-BSA) prior to tracer and protamine injections to inhibit scavenger receptors of the reticuloendothelial system, and the last group receiving preformed heparin protamine aggregates. All animals were examined by scintigraphy. Blood and tissue samples were analyzed for radioactivity. Protamine injection 2 min after heparin tracer application lead to a rapid decline in blood radioactivity. The radioactivity in the liver increased from 17% for the control to 43% after protamine application. Injection of mal-BSA prior to protamine prevented tracer accumulation in the liver and increased urine excretion (34% versus 20%). In vitro preformed heparin-protamine precipitates were rapidly trapped in the liver. We present evidence that, like the polyanionic heparin, polyanionic heparin protamine complexes are phagocytosed by a scavenger receptor-mediated mechanism by macrophages, predominantly in the liver. The amount, the size, and the charge density of the complexes might trigger a mediator release from macrophages leading to phenomena such as pulmonary hypertension. PMID- 7861774 TI - Effects of hyaluronidase on reducing myocardial infarct size in a baboon model of ischemia-reperfusion injury. AB - Hyaluronidase has been reported to be beneficial in reducing injury to the ischemic myocardium in several experimental studies. This effect may involve an enhancement in either the cardiac blood supply or lymphatic flow or a combination there of. In this experiment, a baboon open chest model of myocardial ischemia and reperfusion was used to determine if treatment with hyaluronidase would result in a reduction in infarct size. Baboons underwent occlusion of the left anterior descending coronary artery for 2 hr. Fifteen minutes after occlusion, a treated group (n = 6) received bovine testicular hyaluronidase (500 national formulary units/kg) i.v. over a 10-min period. The ischemic period was followed by 22 hr of reperfusion. A control group (n = 8) underwent the same protocol minus the hyaluronidase infusion. At the end of the reperfusion period, the hearts were excised and the perfusion bed at risk for infarction was determined by the infusion of a microvascular dye. The hearts were then sectioned and stained for the histological determination of infarct size. The volume of the perfusion bed infarcted was 66 +/- 7% in the control group compared with 42 +/- 10% in the treated group (P > 0.05). In this study using a primate model that has a minimal collateral blood supply, hyaluronidase did not significantly reduce the ultimate infarct size. PMID- 7861775 TI - Do isolated gastric mucosal surface cells from rabbits secrete HCO3-? AB - Only indirect observations suggest that gastric surface cells secrete HCOH3-, which, if the case, should result in an alteration of intracellular pH. This study attempts to determine if HCO3- transport is notable in intracellular pH regulation by isolated surface cells. Maintenance of cellular pH during perfusion with HCO3(-)-free Ringer's solution is unaffected by either the absence of Cl- or the presence of an inhibitor of HCO3- transport, 4,4'-diisothiocyanostilbene-2-2' disulfonate (DIDS). This implies the absence of Cl-/HCO3- exchange and HCO3- transport related to Na+. Addition of HCO3-/CO2 to the perfusate results in acidification due to CO2. The pH then drifts upward, which is prevented by amiloride, an inhibitor of Na+/H+ exchange. Calculated H+ efflux is not significantly affected by HCO3-/CO2. Removal of HCO3-/CO2 results in alkalinization, which is unaffected by the absence of Cl-. Alkalinization following HCO3-/CO2 removal is significantly impaired by acetazolamide. Once alkalinization occurs, the pH declines slowly and is unaffected by a Cl(-)-free perfusate or amiloride or conductance but is markedly accelerated by a Na(+)-free perfusate. The latter is prevented by amiloride but not by DIDS. Thus, under isolated conditions, gastric mucosal surface cells do not appear to be a major source of HCO3- secretion. Alkalinization of the cells can occur as a result of carbonic anhydrase activity, but the alkalinization is maintained by an extracellular Na+ gradient that prevents exchange of intracellular Na+ with extracellular H+. PMID- 7861776 TI - Administration of systemic or local interleukin-2 enhances the anti-tumor effects of interleukin-12 gene therapy. AB - Interleukin-12 (IL-12) is a cytokine with a wide variety of immunoregulatory activities. These include stimulation of interferon-gamma production, cytolytic activity of natural killer (NK) cells and T-cell subsets, the development of cellular immunity, and induction of maturation of Th1 cells. IL-12 also has potent anti-tumor activity in vivo. In the present study the possibility of enhanced anti-tumor activity was examined using a combination of local IL-12 by cytokine gene therapy at the tumor site, combined with systemic or local IL-2 delivery. NIH 3T3 fibroblasts transfected with the genes for both subunits of IL 12, p35 and p40, were used as the source of IL-12 therapy producing 240 HLRU/10(6) cells/48 hr. In the first part of the study the effect of different regimens of systemic IL-2 delivery with local IL-12 administration on the size and growth rate of subcutaneous MCA-105 murine sarcoma was examined. Local IL-12 alone reduced the sizes of tumors after 32 days from 163 to 26.8 mm2 (P < 0.002). Adding the longer-acting polyethylene-glycol-modified IL-2 (PEG IL-2; 30,000 IU) for 5 days prevented the development of tumors in all treated mice compared to 1/3 mice treated with PEG IL-2 alone and 3/6 mice with IL-12, but this was a highly toxic therapy and most of the animals died. Administration of 60,000 IU of IL-2 on Days 1-5 postinoculation of tumor, delivered with IL-12 gene therapy, reduced the tumor growth rate compared to animals treated with IL-2 alone (P < 0.02) or IL-12 (0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861777 TI - The interaction between endothelium-derived relaxing factor (EDRF) and eicosanoids in the regulation of the mesenteric microcirculation. AB - Locally produced eicosanoids and endothelium-derived factors are believed to be the mediators of vascular tone of various vascular beds including the mesentery. Using a small vessel isometric myograph which allows direct measurement of microvascular reactivity, the interaction of eicosanoids and endothelium-derived relaxing factor (EDRF) in regulating vascular tone of mesenteric microcirculation of the rat was characterized. The microvascular response to various vasoactive agents before and after inhibition of prostacyclin production with indomethacin (INDO, 5 microM) and inhibition of EDRF synthesis with N omega-nitro-L-arginine methyl ester (L-NAME, 50 microM) was compared. Analysis of dose-response curves for prostaglandin F2 alpha (PGF2 alpha), U46619, a stable thromboxane analog, and norepinephrine (NE) after pretreatment with INDO demonstrated that inhibition of endogenous eicosanoids significantly attenuated the vasoconstrictor response to PGF2 alpha and U46619 but not to NE. Inhibition of EDRF synthesis with L-NAME potentiated the vasoconstrictor response to PGF2 alpha, U46619, and NE. These results suggest that EDRF acts as the primary mediator of vasodilator tone in the mesenteric microcirculation rather than vasodilator cyclooxygenase products such as prostacyclin. It also appears that the vasoconstrictor action of PGF2 alpha and U46619 may be mediated by a release of an endogenous indomethacin-sensitive factor. PMID- 7861778 TI - Differential expression of protein kinase C isoforms in human colorectal cancers. AB - Protein kinase C (PKC), a serine/threonine kinase central to signal transduction, is implicated in tumor promotion. At present, 10 PKC isoforms have been cloned but their precise tissue-specific role has yet to be defined. In order to determine if PKC is reduced in colorectal cancers (CRC) and if specific PKC isoforms are altered in different stages of human CRC progression, total RNA was extracted from human primary CRC, liver metastases, paired normal mucosa, and liver as well as CRC cell lines and examined for specific PKC isoform mRNA expression. PKC-alpha, beta II, delta, epsilon, eta(L), theta, and zeta were expressed in all tissues examined, while PKC-beta I was not detected. PKC-alpha, beta II, delta, epsilon, and zeta were decreased in most primary CRC. However, the reduction in PKC-beta II was greatest in advanced primary CRC (P < 0.05). Although PKC-gamma was detected in about 29.6% of primary CRC and liver metastases, it was absent from all corresponding normal tissue. In addition, a second band hybridizing to our PKC-gamma probe was uniquely present only in cancerous tissue and not in brain control, suggestive of alternative splicing. PKC-alpha, delta, epsilon, and zeta were present in all cell lines. PKC-beta I/II were both uniformly absent from all cell lines. Since mRNA expression for most PKC isoforms is decreased in CRC, the previously reported decreases in overall PKC activity in CRC are not solely due to a post-translational enzyme modification.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861779 TI - Pectin improves colonic function in rat short bowel syndrome. AB - Short bowel syndrome is characterized by weight loss, diarrhea, and malabsorption. Pectin, a highly fermentable fiber, improves small and large bowel mucosal structure, prolongs intestinal transit, and decreases diarrhea. This study determined if the addition of citrus pectin to an enteral liquid diet (LD) improved structure and absorptive function in the rat jejunum and colon following massive intestinal resection. Twenty-one male Sprague-Dawley rats underwent placement of gastrostomy tube for isocaloric, isonitrogenous feeding and either 60% small bowel and cecal resection or small bowel transection with anastomosis. Animals in each group were then randomly and equally assigned to receive either LD (Enercal Plus, Wyeth) or LD supplemented with 2% citrus pectin for 7 days. Study variables included body weight change, percentage of stool solidity, jejunal villous height (JVH) and crypt depth, colonic crypt depth (CCD), and colonic short-chain fatty acid content (SCFA). Jejunal [14C]glucose absorption and colonic [3H]H2O absorption were measured by a dual in vivo perfusion assay. Resection significantly (P < 0.05) decreased body weight, stool solidity, and colonic SCFA content; enlarged structure (JVH, CCD); and increased absorptive function in the remaining bowel. Pectin significantly decreased (P < 0.05) body weight loss, increased (P < 0.05) stool solidity, and improved (P = 0.05) colonic water absorption following resection without significantly altering mucosal structure. It is concluded that pectin improves colonic absorptive function following massive bowel resection in the rat. PMID- 7861780 TI - Ethics of research training for NIH T32 surgical investigators. AB - As part of the revised curriculum of the NIH T32 Training Grant mechanism, 6 hr of formal instruction in ethics of research are now required. We therefore implemented a four-session seminar (6 hr total time) structured around assigned readings, didactic presentations, and group discussions. The objective of this research project was to assess whether this new program provided our trainees with a framework for ethical conduct in research. Twelve trainees completed the ethics course; 8 trainees who had not yet taken the ethics course served as a control group. All trainees answered a 72-item questionnaire of our own design that examined a variety of issues in research ethics. We compared the responses of seminar participant and nonparticipant groups using the Fisher exact test and Student t test for nominal and ordinal data, respectively. Both groups of trainees perceived that too much emphasis was placed on quantity rather than quality of publications. Both groups felt that this pressure emanated from department chairmen rather than laboratory mentors (P < 0.0001). In contrast to these shared perceptions, the two groups demonstrated many differences in their comprehension of research ethics. For example, compared to the controls, trainees who participated in the ethics course believed that they could define potential NIH standards for data storage and research mentorship (P < 0.05), understood gratuitous manuscript authorship (P < 0.05), were comfortable in dealing with outlier or discordant data (P < 0.10), and, most pertinently, were fully prepared to seek third-party input into an ethical dilemma involving their own work (P < 0.006).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861781 TI - Venous air embolism and the central venous catheter. PMID- 7861782 TI - Basic concepts of antioxidant therapy. PMID- 7861783 TI - A patient with end-stage renal disease and a neck mass. PMID- 7861784 TI - Post-transfusion purpura. PMID- 7861785 TI - Blunt injury to the subclavian artery. PMID- 7861786 TI - Benign manifestations of asbestosis. PMID- 7861787 TI - Asleep at the wheel: fatigue usually wins with deadly results. PMID- 7861788 TI - Loss prevention case of the month. Surgeon or system--malpractice. PMID- 7861789 TI - School days, school days ... those not so healthy school days. PMID- 7861790 TI - Who will provide your income if you can't work? Disability income insurance: the coverage that works when you can't. PMID- 7861791 TI - EEG topography of acute ethanol effects in resting and activated normals. AB - Acute effects of ethanol on spectral characteristics of the EEG were studied using 18 recording sites and topographic mapping. The EEG was recorded both at rest and during a mental arithmetic task. Healthy young male volunteers were randomly assigned to an ethanol (n = 22) or a placebo (n = 15) group. The ethanol group received a total dose of 1.0 g/kg, divided into two equal doses given 75 minutes apart. and measurement sessions took place at baseline and after each dose. The placebo group underwent a similar schedule. Power in the theta, alpha and beta bands all increased in the ethanol group, but only the theta and beta bands clearly separated ethanol from placebo. Alpha increases were seen in the placebo group as well. The ethanol-induced changes were greater in the left hemisphere than in the right, having the effect of attenuating the right-over left asymmetry seen at baseline. Differences between ethanol and placebo were more marked in the mentally activated condition, since the changes seen at rest were inhibited by the activation in the placebo group, but not in the ethanol group. The results indicate (1) that ethanol induces a less differentiated pattern of activity within the brain at rest, and (2) that it impairs the capacity to activate the brain under the challenge of a mental task. PMID- 7861792 TI - Outcomes of a primary prevention project for business and professional women. AB - This article presents the results of an alcohol abuse prevention project targeting business and professional women. Pre-, post- and follow-up surveys of alcohol use, negative consequences and uses, and knowledge of alcohol were analyzed. Although changes in self-reported negative consequences and information about alcohol occurred in both groups, changes in the experimental group occurred earlier (during the intervention period). The experimental group also showed a significant decline in three unhealthy reasons for drinking. there was no change in alcohol consumption levels. In the context of primary prevention the lack of a change in consumption, in a group of light to moderate drinkers, is not unexpected. Other, positive outcomes suggest that the prevention activities were effective. Assessment of the value of the project is considered in light of the finding that negative behaviors did not increase among members of the control group. The results suggest that business and professional women are not developing alcohol-related problems at high rates. PMID- 7861793 TI - Treatment/self-help for alcohol-related problems: relationship to social pressure and alcohol dependence. AB - In a 1984 national survey of U.S. adult drinking practices and problems, social pressure to change one's drinking behavior was significantly related in men to a history of alcohol treatment or self-help (AA), as was severity of alcohol dependence. When dependence was added to a model already including social pressure as a predictor of treatment, the fit of the model to the data was significantly improved. Implications of the findings for diagnostic criteria used to define alcohol dependence are discussed, as well as the relationship of the findings to a theoretical model of illness behavior. PMID- 7861794 TI - Psychometric and biographical correlates of drunk-driving recidivism and treatment program compliance. AB - The primary objective of this study was to assess the extent to which drunk driving (DUI) recidivism and DUI treatment program compliance could be predicted from psychometric, biographical, drinking history and prior-driving-record variables. These analyses were performed on data from 7,316 DUI offenders initially collected in Sacramento County, California, from September 1977 through January 1981. For most analyses, the recidivism measure was a composite of major convictions (DUI, reckless, hit-and-run), nighttime (6 PM-6 AM) and alcohol related accidents during the 4-year interval following treatment assignment. The prediction of recidivism was highly significant for both the construct sample and the 25% cross-validation sample. The predictive accuracy was low, however, as evidenced by multiple Rs of < .30. The predicted rates of recidivism generated for each individual by the regression equation were cross tabulated by other criteria of interest, including total accidents and total injury and fatal accidents. Offenders at high risk of recidivating had substantially higher rates of accidents. The results indicate that reasonably accurate prediction of recidivism is only possible for discriminating between offenders at the extremes of the recidivism expectancy distribution. The above approach was also used to isolate factors predictive of program compliance (successfully completing treatment). In all cases, the prediction of compliance was highly statistically significant. In general, compliance was much more predictable than was subsequent DUI recidivism. Those offenders having a high probability of being noncompliant were much more likely to recidivate and have accidents than were those with favorable compliance expectancies. PMID- 7861795 TI - Hit the bottle and run: the role of alcohol in hit-and-run pedestrian fatalities. AB - Alcohol is associated both with motor vehicle crashes and with crime. We examine the role of alcohol in hit-and-run collisions, based on pedestrian fatalities recorded in the Fatal Accident Reporting System. In 19% of all pedestrian fatalities in 1989 and 1990, the driver left the scene. Time of the accident is available for all pedestrian fatalities. Strong evidence for the influence of alcohol on hit-and-runs is the greater proportion of hit-and-runs at night and during the weekend, two periods when drivers are more likely to be drinking. Half of hit-and-run motorists are eventually identified. Compared to those who remain at the scene, the identified hit-and-run motorists are far more likely to have had a previous arrest for driving while intoxicated. They are also disproportionately young and male, two factors associated with drinking and driving. Only a fraction of drivers are tested for blood alcohol concentration (BAC); those who left the scene are more likely to have a positive BAC. Two theories--the rational decision theory and the personality theory--help explain why drunk drivers are more prone to run after hitting a pedestrian. PMID- 7861796 TI - "Resolv'd to drink no more": addiction as a preindustrial construct. AB - The notion that alcohol is potentially addictive dates not from the late eighteenth century but from the early seventeenth century at the very least, as does the related notion that habitual drunkenness constitutes a "disease" in its own right. English pamphlets and sermons from the latter period would suggest that the two notions were first advanced by clergymen and other moralists, and only later found acceptance in the British and American medical communities. Seen in this light, the American physician Benjamin Rush (c. 1745-1813) was less an innovator in advancing the notion of addiction than the last great voice in a tradition already 150 years old. PMID- 7861797 TI - The use of the CAGE questionnaire in a cohort of homosexually active men. AB - The prevalence and correlates of alcohol-related problems measured by the CAGE questionnaire were investigated in a population of 249 homosexually active men at a Boston community health center. Two hundred eight men (79.4%) reported alcohol use during the past 6 months and 22.9% (27.4% of alcohol users) were CAGE positive (two or more positive responses). Increased frequency of alcohol use was strongly associated with CAGE positivity (p < .001). Controlling for frequency of alcohol use, cigarette smoking was independently associated with a positive CAGE score. Other substance use and demographic variables were not independently associated with CAGE problems. PMID- 7861798 TI - How much can data on days with heavy drinking decrease the underestimation of true alcohol consumption? AB - An adjusted quantity-frequency method, with questions on occasions with heavy drinking, was used to estimate the consumption of alcohol during the last 30 days. The purpose was to analyze if it was possible to decrease the underestimation of true alcohol consumption. The questionnaire was mailed to a randomized sample of 1,500 individuals, 20-75 years of age, living in the city of Malmo, Sweden; 930 persons (64.3%) participated. Data on alcohol consumption were validated by comparison to sales of alcohol for the city of Malmo. The estimated per capita consumption of alcohol in the population was equivalent to 77.0% of the registered sale of alcohol in Malmo. By adding days with heavy drinking, the estimated weekly per capita consumption of alcohol among the alcohol consumers increased from 74.5 grams to 77.1 grams (+3.5%; p < .001). Of the alcohol consumers, 15.1% increased their reported consumption. In order to decrease even more the underestimation of the true alcohol consumption, we suggest the use of questions about any alcohol consumption that deviates from the typical consumption of each individual. PMID- 7861799 TI - Alcohol and the Taylor aggression paradigm: a repeated measures study. AB - Acute alcohol intoxication has been shown to increase physical aggression in the laboratory as measured by the Taylor aggression paradigm with independent groups. Because it would be advantageous to use the Taylor paradigm in a repeated measures design to examine individual differences, the present study compared the performance of subjects on two counterbalanced occasions: when they were intoxicated and when they were sober. Order of testing significantly interacted with drug condition for the aggression measures and pain threshold. However, an analysis of the ratio of pain threshold to shock intensity, and to total aggression, revealed the procedure to be useful in understanding one aspect of how alcohol modulates aggression. The results suggest that acute alcohol intoxication interferes with the ability to integrate previously acquired knowledge in the formulation of behavioral strategies. PMID- 7861800 TI - The stress-negative affect model of adolescent alcohol use: disaggregating negative affect. AB - The current study addressed three primary limitations of previous research on the relations among stress, negative affect and adolescent alcohol use. These include failure to distinguish among different types of negative affect, inattention to potential moderators of the relation between affect and alcohol use (e.g., impulsivity), and insufficient utilization of high-risk samples (e.g., children of alcoholics). In the current study, anger, anxiety and depression were found to differentially mediate the relation between stress and alcohol use, such that depression was the only significant mediator (above and beyond the effects of the other two affect measures). Impulsivity was also found to moderate the depression to alcohol use relation such that depressed, impulsive adolescents drank more heavily than depressed, nonimpulsive adolescents or nondepressed adolescents. Research implications include a need for future attention to the unique relations between forms of negative affect and alcohol use and to variables that might moderate these relations. PMID- 7861801 TI - Alcohol habits among teenagers in Sweden: factors of importance. AB - This study of 689 secondary school students (13-16 years of age) in Sweden investigates the association between alcohol habits, the availability of alcohol and age, gender, socioeconomic status, ethnic origin and family structure. Data were obtained by anonymous questionnaires in 1991. The availability of alcohol increased from the seventh grade to the ninth as did the proportion of alcohol consumers and students with regular alcohol consumption. Boys in the seventh and eighth grades showed somewhat more advanced alcohol habits than girls, but in the ninth grade the opposite was seen. Students with more advanced alcohol habits and a higher availability of alcohol more often belonged to a lower socioeconomic strata and they lived more often with a single parent. Students of foreign background drank alcohol (especially wine) more regularly. An association was also found between the parents' liberal attitude toward offering alcohol at home and frequent intoxication and the students' experience of illicitly produced liquor, especially among the youngest students. In spite of the Swedish alcohol policy the availability of alcohol is rather high among young people. Special attention in alcohol preventive work should be paid to girls, young people living with one parent, young people in lower socioeconomic groups and young people of foreign origin. PMID- 7861802 TI - Models of functional organization as a method for detecting cognitive deficits: data from a sample of social drinkers. AB - Literature on the cognitive deficits associated with social drinkers' chronic use of alcohol at moderate to heavy levels is equivocal. As an alternative to detecting impairment through measures of mean performance levels, the functional organization of cognitive skills in infrequent and heavy alcohol users was compared. Subjects (N = 364) were adolescent and young adult participants in a longitudinal study of health status and psychoactive substance use. LISREL was used to identify group invariance in the number and nature of cognitive components underlying performance. Results showed that a model with three cognitive components (general intelligence/abstraction, spatial relations/visual motor speed, and immediate memory) best represented performance in both infrequent use and heavy use groups. There were some group differences in the role of unspecified processing components, but no clear evidence for alcohol related shifts in functional organization was found. The hypothesis of cognitive compensation, which highlights methodological problems in deficit-detection research, is evaluated with respect to the potential value of using changes in functional organization, that is, the latent structure of performance, to uncover the neurotoxic effects of alcohol or other drug use. More definitive tests of the compensation hypothesis will require prospective, within-subject comparisons of functional organization in clinical as well as nonclinical samples. PMID- 7861803 TI - Increases in alcohol-related problems for men on a college campus between 1980 and 1992. AB - A questionnaire concerning alcohol and drug use was mailed to a random sample of male students at the University of California at San Diego in 1980, and similar procedures were used in 1992. Both mailings yielded response rates of approximately 70% (1980: N = 1,024; 1992: N = 721). The data revealed that while the rates of illicit substance use and associated problems decreased significantly between the two time points, the quantity of alcohol consumed per occasion and the prevalence of alcohol-related problems significantly increased during those 12 years. These increases suggest a need for an expanded emphasis on alcohol education at colleges and universities. PMID- 7861804 TI - Gender comparisons of alcohol consumption in alcoholic and nonalcoholic populations. AB - The purpose of this study was to examine the similarities and differences between male and female drinkers in terms of the estimated functional impact of alcohol intake on drinking occasions. Alcohol consumption on drinking occasions was documented in male and female alcoholics and occasional drinkers in face-to-face interviews and also in a general population statewide sample by means of a telephone survey. Expression of ethanol intake in terms of grams of ethanol consumed per kilogram of total body water yielded data consistent with the notion that blood concentrations of ethanol achieved by females on drinking occasions may have been quite similar to the values achieved by males. However, important gender differences were also found in terms of an older age of onset of regular drinking, less frequent alcohol intake and a higher percentage of abstainers among females. PMID- 7861805 TI - Situational influences on cues used to judge intoxication. AB - Subjects' perceptions of cues used to judge intoxication across different drinking settings were investigated. College students (N = 40) were presented with 12 one-paragraph scenarios, four for each of three types of drinking expectancy: tension reduction, social disinhibition and physical impairment. Pilot testing confirmed that the scenarios accurately represented these different expectancies. Subjects rated the importance of 18 cues to intoxication for judging intoxication in each of the 12 scenarios. Results indicated that 15 of the 18 cues were perceived to be differentially important in the three types of situations. These results suggest that subjects apply cues to intoxication differently in different situations. PMID- 7861806 TI - Hassles and uplifts and generalized outcome expectancies as moderators on the relation between a family history of alcoholism and drinking behaviors. AB - The present study examined 85 adult offspring of alcoholics (FH+) and 68 comparison subjects without a family history of alcoholism (FH-) in order to address three questions: (1) Does the relation between hassles and uplifts and drinking differ by gender and/or family history of alcoholism? (2) Do hassles and uplifts and/or generalized outcome expectancies (dispositional optimism and pessimism) moderate the relation between having a family history of alcoholism and drinking behaviors? (3) Do hassles and uplifts and outcome expectancies interact to influence drinking behaviors? The pattern of relations between hassles and uplifts and drinking behaviors and between outcome expectancies and drinking behaviors differed by family history and gender. Hassles were related to increased alcohol consumption for FH+ men only, whereas outcome expectancies were related to indicators of problem drinking for FH+ women only. When the moderating influences of hassles and uplifts and outcome expectancies were examined, both hassles and pessimism were found to moderate the relation between family history and drinking behaviors. In addition, hassles and uplifts and outcome expectancies interactively influenced this relation. These results emphasize the need to examine further both individual and contextual processes in studies examining the risk of the development of alcoholism. PMID- 7861807 TI - Smoking status as the new vital sign: effect on assessment and intervention in patients who smoke. AB - OBJECTIVE: To assess the effect of expanding the vital signs to include smoking status. DESIGN: We prospectively conducted exit interviews with patients at a general internal medicine clinic in Madison, Wisconsin, during a 16-month period from 1991 to 1993. METHODS: Patients were surveyed briefly before (N = 870) and after (N = 994) the implementation of a simple institutional change in clinical practice. This change involved training the staff in how to use progress notepaper with a vital sign stamp that included smoking status (current, former, or never) along with the traditional vital signs. Included in the survey were questions about whether the patient smoked, whether the patient was asked that day about smoking status (by a clinician or other staff), and, for smokers, whether they were urged to quit smoking and given specific advice on how to do so. RESULTS: After expansion of the vital signs, patients were much more likely to report inquiries about their smoking status on the day of a clinic visit (an increase from approximately 58% at baseline to 81% at intervention; P < 0.0001). The vital sign intervention was associated with significant increases in the percentage of smokers who reported that their clinician advised them that day to quit smoking (from approximately 49% at baseline to 70% during the intervention; P < 0.01) and in the percentage who reported that their clinician gave them specific advice that day on how to stop smoking (from approximately 24% at baseline to 43% during the intervention; P < 0.01). CONCLUSION: Expanding the vital signs to include smoking status was associated with a dramatic increase in the rate of identifying patients who smoke and of intervening to encourage and assist with smoking cessation. This simple, low-cost intervention may effectively prompt clinicians to inquire about use of tobacco and offer recommendations to smokers. PMID- 7861808 TI - Stereotactic radiosurgical treatment of cerebral arteriovenous malformations. Gamma Unit Radiosurgery Study Group. AB - OBJECTIVE: To assess the role of clinical factors, size of lesion, site of involvement, and radiation dose in patients with cerebral arteriovenous malformations (AVMs) who underwent stereotactic radiosurgical treatment. DESIGN: We reviewed the results in 121 patients with cerebral AVMs treated with the Leksell "Gamma Knife" between January 1990 and December 1993 at the Mayo Clinic in Rochester, Minnesota. MATERIAL AND METHODS: The following strict dose-volume protocol was used: AVMs 2.0 cm or smaller in diameter (volume, 4.2 cm3 or less) received 20 Gy to the margin of the nidus, those between 2.1 and 3.0 cm in diameter (4.3 to 14.1 cm3) received 18 Gy to the margin, and those that exceeded 3.0 cm in diameter (more than 14.1 cm3) received 16 Gy to the margin. Lesions that involved the brain stem received a radiosurgical dose of 18 Gy or less to the margin. Patients participated in regular follow-up clinical and imaging studies for up to 55 months. RESULTS: Follow-up cerebral angiography in 43 patients demonstrated total obliteration of the AVM nidus in 31 (72.1%), including 5 of 7 (71.4%) who had AVMs with a volume larger than 10 cm3. Clinical follow-up revealed that 111 patients (91.7%) had a stable or improved outcome, 3 had a nonfatal AVM hemorrhage, 2 suffered a fatal hemorrhage, and 2 died of causes not directly attributed to the AVM or radiosurgical treatment. Two patients had new or increased, nondisabling neurologic deficits as a result of treatment, and one patient had a temporary partial eyelid ptosis. CONCLUSION: Our findings suggest that previous theories about the relationship between AVM size and rate of obliteration after radiosurgical treatment may need revision. Our experience confirms that radiosurgical treatment for cerebral AVMs is safe and effective, even in cases for which the latency period before obliteration is longer than 2 years. PMID- 7861809 TI - Quantity of coronary artery calcium detected by electron beam computed tomography in asymptomatic subjects and angiographically studied patients. AB - OBJECTIVE: To determine the prevalence and quantity of coronary artery calcium (CAC) in asymptomatic subjects from the general population, to identify asymptomatic subjects without risk factors for coronary artery disease (CAD) with CAC scores in the top quartile of the distribution, and to compare CAC scores in patients who underwent angiography with percentiles in asymptomatic subjects of the same age and sex. DESIGN: We studied two samples from Rochester, Minnesota, which consisted of 772 asymptomatic subjects from the general population and 145 patients who underwent angiography, all of whom were 20 to 59 years of age. METHODS: Asymptomatic subjects were classified on the basis of their CAD risk profile. All subjects in both study samples underwent electron beam computed tomography. Age- and sex-specific calcium score percentiles were calculated in the asymptomatic sample. RESULTS: CAC prevalence in the asymptomatic subjects was lower in female than in male subjects and increased with advancing age. Of the asymptomatic sample, 8% had a low-risk profile with calcium scores in the top quartile of the distribution. More patients than expected in the angiography sample had calcium scores above the 50th through 95th score percentiles. CONCLUSION: The quantity of CAC was substantially increased in patients who underwent angiography. Subjects with large amounts of CAC but without known CAD risk factors may be a valuable subset of the population to investigate for previously unidentified CAD risk factors. PMID- 7861810 TI - Sweet's syndrome: systemic signs and symptoms and associated disorders. AB - OBJECTIVE: To characterize the findings associated with acute febrile neutrophilic dermatosis (Sweet's syndrome [SS]) and the response of SS to treatment. DESIGN: We retrospectively reviewed 48 cases of SS encountered at the Mayo Clinic between 1980 and 1992. MATERIAL AND METHODS: Histopathologic specimens and medical records were studied to determine initial manifestations, patterns of involvement, systemic signs and symptoms (including mucosal, musculoskeletal, hematologic, pulmonary, hepatic, and renal findings), and conditions associated with SS. RESULTS: In patients with SS, the typical manifestations are the acute onset of tender, erythematous or violaceous nodules or plaques in association with fever, leukocytosis, and dermal neutrophilia. In our study group, the cutaneous lesions most frequently involved the arms and legs. Of our 48 patients, 26 (54%) had a hematopoietic, plasma cell, or malignant disorder, and many of these patients had associated anemia, especially the male patients. No single laboratory finding specifically indicated an association with serious systemic disease. Most patients were treated with a tapering dose of prednisone, which yielded a good response. CONCLUSION: Clinical acumen and appropriate laboratory tests are the main requirements for detection of hematologic disorders, internal malignant diseases, or other systemic conditions associated with SS. PMID- 7861811 TI - Clinical effects of intravenously administered dantrolene. AB - OBJECTIVE: To compare side effects after intravenous administration of dantrolene sodium in subjects susceptible to and those nonsusceptible to malignant hyperthermia (MHS and MHN, respectively). DESIGN: We studied two groups, six patients thought to be MHS and six assumed MHN subjects, and analyzed their responses to intravenously administered dantrolene. MATERIAL AND METHODS: Dantrolene (3 mg/kg) was administered slowly into an antecubital vein, and blood samples were withdrawn from the other arm at 5 and 25 minutes after infusion. Shortly thereafter, all subjects underwent a clinical neurologic assessment, and side effects were graded subjectively by the study participants. RESULTS: Side effects occurred in all subjects. Visual symptoms occurred more commonly in MHN than in MHS subjects. Subjective muscle weakness of the extremities, dizziness, and fatigue occurred more commonly and were more severe in MHS patients than in MHN subjects. CONCLUSION: In patients recovering from an episode of malignant hyperthermia for which dantrolene has been administered, these side effects should be considered. Although the presence of side effects does not outweigh the usefulness of this drug in treating malignant hyperthermia, it may be a consideration in deciding whether to administer dantrolene prophylactically before surgical procedures in known or suspected MHS patients. PMID- 7861812 TI - Inhaled nitric oxide therapy. AB - OBJECTIVE: To review the basic science, physiology, toxicity, and delivery of inhaled nitric oxide (NO). DESIGN: A literature review of inhaled NO is presented, and a brief discussion of current clinical applications is included. RESULTS: Inhaled NO is a new investigational drug used for selective vasodilation of the pulmonary vasculature. It mimics the effects of endogenously produced endothelium-derived relaxing factor. In addition to selective pulmonary vasodilation, inhaled NO can improve hypoxemia by improving ventilation-perfusion relationships within the lung. The doses of inhaled NO that produce improvements in oxygenation are lower than those needed to produce maximal vasodilation. Inhaled NO is being used in the intensive-care unit to treat critically ill patients with pulmonary hypertension or hypoxemia associated with ventilation perfusion imbalance. It is also being used in the cardiac catheterization laboratory as a diagnostic tool. Few adverse effects have been associated with the use of inhaled NO. CONCLUSION: Despite a lack of randomized, controlled studies that show improved outcome in comparison with traditional treatments, inhaled NO seems to be an effective new therapy for patients with pulmonary vasospasm or hypoxemia associated with ventilation-perfusion imbalance. It may also prove to be a valuable diagnostic tool in the cardiac catheterization laboratory. PMID- 7861813 TI - Primary lymphoma of the spinal cord. AB - Non-Hodgkin's lymphomas arising in the spinal cord are extremely rare. Only eight single case reports have been well confirmed in the literature. Herein we describe a 59-year-old woman with symptoms attributable to a spinal cord lesion. Physical examination revealed neurologic deficits but no evidence of tumor elsewhere. Although several imaging studies were performed, only magnetic resonance imaging with use of gadolinium revealed the exact site and extent of the lesion. Laminectomy and direct examination of the spinal cord disclosed a discolored region at the level of the 11th thoracic vertebra. A biopsy specimen was obtained, and pathologic examination revealed an intermediate grade, mixed cell lymphoma of T-cell origin. Radiotherapy was administered to the lesion and adjacent region of the spinal cord with use of 6-MV photons and an anteroposterior-posteroanterior technique; the total dose was 45 Gy in 23 fractions. No chemotherapy was given. After 3 years of follow-up, the neurologic signs and symptoms were stable, and repeated magnetic resonance imaging with use of gadolinium showed no residual tumor. In addition to the case report, we review the literature on primary lymphomas of the central nervous system and discuss treatment recommendations. PMID- 7861814 TI - Systemic monocyte and T-cell activation in a patient with human parvovirus B19 infection. AB - Infection with human parvovirus B19 induces a biphasic disease. The initial phase has been associated with viremia. During the second phase of the disease, a spectrum of clinical syndromes can manifest, including erythema infectiosum, perinatal complications, and symmetric arthropathy that resembles rheumatoid arthritis. Although investigators have suspected that some of the second-phase symptoms are related to immune complex formation, the pathogenesis of parvovirus B19-induced clinical manifestations is not understood. Herein we describe a 63 year-old woman with malaise, fever, and symmetric polyarthritis who had IgM antibodies specific for parvovirus B19. Messenger RNA (mRNA) specific for interleukin (IL) 1 beta, IL 6, and interferon-gamma (IFN-gamma) was detected by polymerase chain reaction. Transcript concentrations were semiquantified by serial dilution of cells and determination of the minimal number of cells that provided a positive signal. Concentrations of IL 1 beta and IL 6 mRNA in peripheral blood mononuclear cells collected during acute disease were increased by the factor of 32 and 8, respectively. IFN-gamma was detected at a 16-fold increased concentration. Two months later, after the patient had experienced complete recovery, production of monokines and IFN-gamma was almost normalized. These data raise the possibility that acute parvovirus B19 infection is characterized by a widespread and systemic activation of monocytes, T cells, and natural killer cells. The correlation of increased cytokine mRNA levels and clinical symptoms suggests a potential role of proinflammatory monokines and lymphokines in disease manifestations. PMID- 7861815 TI - Current concepts in anticoagulant therapy. AB - An understanding of the international normalized ratio (INR)--which was developed to standardize reporting of the prothrombin time (PT) and provide consistent regulation of anticoagulation--is important. The recommended therapeutic range for the INR (which is calculated from the patient's PT, a mean control PT, and the international sensitivity index) for oral anticoagulant treatment of most conditions is 2.0 to 3.0. In patients with mechanical cardiac valves, the INR should be at least 2.5 to 3.5. A common cause for progression of venous thromboembolic disease and treatment failure is inadequate heparinization during the first day of treatment. Therefore, an intravenous bolus of 5,000 to 10,000 U of heparin should be administered before a maintenance infusion is initiated. Also during the first day of treatment, warfarin therapy can be implemented. Overlap treatment with heparin and warfarin for 4 or 5 days is recommended. Low molecular-weight heparins, a new class of anticoagulants, have been shown to be more effective than standard heparin in preventing venous thrombosis in orthopedic surgical patients, but at a higher cost. Patients with mechanical cardiac valves who are receiving anticoagulant therapy and are scheduled for noncardiac operations must have a risk-to-benefit assessment of the need for continuous anticoagulation performed preoperatively. Many of these patients can safely discontinue warfarin therapy for several days as outpatients before the surgical procedure. Preoperative heparin therapy and warfarin withdrawal in the hospital are recommended only for those patients with cardiac valves at high risk for systemic embolization (with a mitral valve prosthesis, cardiomyopathy, or previous thromboembolism). The concurrent use of certain drugs or presence of comorbid conditions can predispose to hemorrhagic complications of anticoagulant therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861816 TI - Ulf von Euler--norepinephrine and the Nobel Prize. PMID- 7861817 TI - Mechanisms of adenosine-mediated actions on cellular and clinical cardiac electrophysiology. AB - OBJECTIVE: To provide insights into the molecular mechanisms of adenosine mediated cardiac cellular electrophysiology and how information about these mechanisms can be used to facilitate diagnostic and therapeutic approaches to various clinical arrhythmias. DESIGN: A review of (1) adenosine metabolism and receptors in the cardiac system, (2) adenosine-mediated signal transduction pathways in the regulation of cellular electrophysiology in various cardiac cell types, and (3) the clinical usefulness of adenosine in cardiac electrophysiology is presented. RESULTS: The effects of adenosine on cardiac electrophysiologic properties are consequences of complex interactions among the specific cardiac target structures, the density and type of adenosine receptors, and the effector systems. The easy application of adenosine and its short half-life, favorable side-effects profile, and electrophysiologic properties make it an excellent diagnostic and therapeutic tool for the initial assessment of various tachyarrhythmias. CONCLUSION: The direct adenosine-activated KACh (potassium acetylcholine) channel signal transduction system explains the effects of adenosine on the sinus node, atrioventricular node, and atrial myocardium. The indirect adenosine-inhibited adenylate cyclase system accounts for its negative inotropic effects on the catecholamine-entrained contractility in atrial and ventricular myocardium. Because of the recent purification and cloning of adenosine receptors and subunits of G proteins, additional adenosine-mediated electrophysiologic mechanisms can be explored. PMID- 7861818 TI - 79-year-old woman with blue toes. PMID- 7861819 TI - Influences of American philosophy and history on the practice of American medicine. PMID- 7861820 TI - Is it not time to make smoking a vital sign? PMID- 7861821 TI - Stereotactic radiosurgical procedures for arteriovenous malformations of the brain. PMID- 7861822 TI - Renal biopsy. PMID- 7861823 TI - Single voided urine protein/creatinine ratio. PMID- 7861824 TI - The impact of an ambulatory firm system on quality and continuity of care. AB - The author assessed the effects on quality and continuity of care at a Veterans Affairs hospital as a result of its conversion to an interdisciplinary firm system. Before the firm system was implemented, ambulatory care at the hospital was provided in two medicine clinic areas and in one unscheduled "walk-in" clinic. Care for intercurrent illnesses was frequently not coordinated. The staff from eight clinical services were involved in restructuring into three, interdisciplinary firm teams. These firm teams were created without the addition of new staff. Quality was defined by patient satisfaction, staff satisfaction, re admissions within 10 days of a hospital discharge, and length of visit. Continuity was defined by percentage of visits to the primary care team (defined as the physician or the physician paired with midlevel practitioner if applicable). Patient satisfaction increased from 4.43 to 4.84 (5-point Likert scale, P < .001). Staff satisfaction increased from 4.3 to 6.24 (7-point Likert scale, P < .001). Re-admissions within 10 days of hospital discharge decreased by 28% (P < .01). Length of visit decreased by 9.5% (P < .0001). Continuity improved from 47% to 69% of visits to the primary care team (P < .002). These results more than justified the staff time needed to convert to a firm system. PMID- 7861825 TI - Reaction to "talking" computers assessing health risks. AB - The authors examined reactions to AVIVA-a talking computer that assesses health risk, gives priorities for risk reduction, discusses risk reduction methods, and refers callers to additional information. Subjects' reactions to AVIVA were compared to receiving health information from magazines, television, or health professional. Data were collected from 96 randomly chosen employees of Cleveland State University. Employees were invited to participate based on a stratified sample that encouraged enrollment of men and women and enrollment of faculty, professional and nonprofessional staff. The majority (71%) of subjects with access to AVIVA used it. Those who did not use AVIVA gave various reasons; less than 4% did not participate in AVIVA because they objected to a computer giving advice regarding health risks. Subjects rated AVIVA as more accurate, easier to understand, more convenient, more affordable, easier to use, and more accessible than health education received from television, magazines, or health professionals. None of the at-risk subjects sought additional information from a library of videotapes available to them. Furthermore, there was no statistically significant difference between the control and the experimental groups in the intent to reduce risk factors. Therefore, despite use and satisfaction with AVIVA, the authors concluded that there was no impact on subjects' behavior or intent to change behavior. PMID- 7861826 TI - Can early re-admission rates accurately detect poor-quality hospitals? AB - There is widespread interest in using external quality measures, such as early re admission rates (ERRs), to evaluate hospital quality. To evaluate the feasibility of using ERRs to identify poor-quality hospitals, a Monte Carlo simulation model was developed that describes the predictive power of ERRs for the 190 hospitals in Michigan using different assumptions concerning the distribution and variability of quality problems, the number of years of data aggregated, and unmeasured case-mix differences. The ability of ERRs to distinguish 171 average quality hospitals from 19 poor-quality hospitals (assigned to have 5% vs. 15% premature discharges) was evaluated. First, the largest diagnosis-related groups (DRGs) were studied to determine if they included cardiac, gastrointestinal, pulmonary, and neurologic diseases. Despite using the highly optimistic assumptions that premature discharges are readmitted 50% more frequently than appropriately timed discharges and that no ERR variation was caused by unmeasured case-mix differences between hospitals, the results were poor. For example, for DRG 127 (heart failure), high ERR outlier status (using a .05 probability cutoff) had a positive predictive value of only 36%, meaning that approximately two thirds of hospitals labeled "poor-quality" (high ERR outliers) were false positive results. Next, we repeated the simulation with sample sizes aggregated for all medical DRGs. The positive predictive value was 72%, but was very sensitive to ERR variability due to non-quality-related factors (e.g., unmeasured case mix). The positive predictive value decreases to 45% if unmeasured case mix accounts for even 10% of observed hospital ERR variation. The circumstances under which DRG-specific ERRs would be useful to detect poor-quality hospitals are unlikely to occur. Even collapsing to all medical DRGs, ERRs are likely to be accurate predictors only if quality differences are quite large and if unmeasured case-mix differences account for a small amount of interhospital variation in ERRs. PMID- 7861827 TI - Outpatient surgical utilization in Veterans Affairs hospitals, 1981-1989. AB - In the 1980s, there was a large increase in the percentage of surgical operations performed in the United States without an overnight hospital admission. This shift may have been related to changes in reimbursement for outpatient surgery; studies of this relationship have had conflicting results. The Department of Veterans Affairs (VA) has a budgeting strategy significantly different from reimbursement strategies used by nonfederal hospitals. The VA strategy underwent changes in terms of budgeting for outpatient surgery in the 1980s. Data from the American Hospital Association (AHA) Annual Survey of Hospitals collected during the years 1981 through 1989 inclusive were analyzed in an effort to examine VA outpatient surgical utilization and to compare changes in VA outpatient surgical utilization with changes in outpatient surgical utilization in the nonfederal sector. The VA had an apparent rapid expansion of outpatient surgical utilization in the mid-1980s compared with the nonfederal sector. This increase occurred without a concomitant decrease in inpatient surgical procedures. This apparent rapid expansion may represent a combination of real changes in surgical utilization, changes in utilization of services not traditionally thought to be surgical but counted as such by VA hospitals, and changes in VA record-keeping. All of the components of this expansion may have been accelerated by the implementation of the VA Resource Allocation Methodology in 1985 and 1986. PMID- 7861828 TI - Diffusion of laparoscopic cholecystectomy among general surgeons in the United States. AB - Introduced in 1989, laparoscopic cholecystectomy has rapidly become the treatment of choice for symptomatic gallstones. This study describes the diffusion of laparoscopic cholecystectomy among general surgeons; assesses the importance of various reasons for surgeons adopting the procedure; and examine the influence of surgeon, practice, and health care market characteristics on the timing of adoption. The data were obtained from a survey of a national sample of surgeons. Most surgeons (81%) adopted laparoscopic cholecystectomy by early 1992. More than three fourths of adopters identified the desire to keep up with the state-of-the art and improved patient outcomes as very or extremely important reasons for adoption. Results of proportional hazards regression analysis indicate that individual surgeons' adoption behavior generally was consistent with expected utility maximization in an uncertain new technological environment. Of particular interest, fee-for-service payment and more competitive practice settings and markets were associated with earlier adoption. These findings suggest that the "technological imperative" and surgeons' perception of the relative clinical and financial advantages of laparoscopic cholecystectomy were important reasons for the rapid diffusion of laparoscopic cholecystectomy. Policies that accelerate current trends toward payment of physicians based on salary or capitation and promote the growth of multispecialty group practice could slow the diffusion of new physician-based product innovations in health care. PMID- 7861829 TI - Papanicolaou smear recommendations, patient complaints, and patient satisfaction in managed-care medical organizations. AB - This study sought to determine whether primary-care physicians, practicing in different types of manage-care medical organizations, wer recommending Papanicolaou (Pap) smear screening to their patients. The author also wished to determine whether Pap smear recommendation rates correlated with characteristics of the organizations, with complaint rates, or with survey-based satisfaction measures. Randomly selected medical records (N = 10,978) were audited for women older than 18 years of age, insured by a single California health maintenance organization, who were being cared for by 81 medical organizations. It was determined whether women with an established primary-care physician were receiving recommendations for Pap smear testing within a 2-year period. Information on quality-related patient complaints from these organizations also was tabulated, and a telephone-based patient satisfaction survey on 1,700 members from the 46 largest organizations was performed. Overall, the study's Pap smear standard was met 83.2% of the time, with a range of 30% to 100% between organizations. Performance was unrelated to organization size, type, number of patients, percentage of board-certified physicians, or whether the organization permitted self-referral to an obstetrics/gynecology physician. Performance was also unrelated to complaint rates or survey measures of patient satisfaction. Performance was, however, positively correlated with the number of prepaid patients per primary care physician (r = 0.28, P = 0.01). Complaint rates and survey satisfaction measures were strongly correlated with each other (r = -0.48 and -0.57, P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861830 TI - Lifetime patterns of payment for nursing home care. AB - Although much is known about who pays the annual aggregate nursing home bill, relatively little is known about payment-source patterns of individuals during their lifetimes. In this article, lifetime payment-source patterns are analyzed for elderly nursing home users, particularly the extent to which they spend down assets to become eligible for Medicaid. During their lifetimes, 44% of persons who use nursing homes after 65 years of age start and end as private payers, 27% start and end as recipients of Medicaid benefits, and 14% spend down assets to become eligible for Medicaid benefits. Although still a relatively small proportion, the asset spend-down estimate based on lifetime data is 2.5 times previous national estimates based on data for single nursing home stays. The projected risk of spending down assets in nursing homes for all persons who turn 65 years of age in 1995, including users and nonusers of nursing homes, is slightly more than 6%. Equally or more important for policy is that 17% of all persons who turn 65 years of age can expect to end up using a nursing home and receiving Medicaid reimbursement. Of those, more than 3 in 5 will have entered the nursing home already eligible for Medicaid benefits. PMID- 7861831 TI - Minimum data needed on patient preferences for accurate, efficient medical decision making. AB - Involving patients in their health care decisions improves patient satisfaction and outcomes, but can be costly because of the materials and time needed to discuss the many issues that constitute a medical problem. The authors present a framework for identifying the minimum data needed on patient preferences for accurate medical decision making. The method is illustrated for the decision of whether patients with end-stage renal disease should undergo short or long hemodialysis treatments. The value of health states to patients was modeled as a function of six outcomes: survival, uremic symptoms, hospital days per year, the inconvenience associated with long dialysis treatment duration, presence of hypotension during dialysis, and presence of other symptoms during dialysis. The relative importance of each outcome was characterized in a value function by weights referred to as preference-scaling factors. These factors were varied at random over a uniform distribution to simulate different patterns of patient preferences on the six outcomes. The decision model's recommendation was recorded for each simulation. Classification and regression-tree (CART) and stepwise logistic regression analyses were applied to these recommendations to determine the scaling-factor levels that predict short or long treatments. Knowledge of scaling factors on only the inconvenience of long dialysis treatment duration, the worst alive state of health on hemodialysis, and presence of hypotension identified the correct treatment in more than 97% of simulations. Fifty-five patients undergoing hemodialysis were then surveyed for their scaling factors on the six dimensions of well-being. When patients' scaling factors were applied to the predictive rule generated by CART using simulated scaling factors, more than 94% of treatment decisions were classified correctly--sensitivity and specificity of predicting long dialysis were 89% and 100%, respectively. These statistical techniques applied to results of a decision model help identify the minimum data needed on patient preferences to involve patients in efficient and accurate decisions about their health care. PMID- 7861832 TI - Improving primary care in academic medical centers. The role of firm systems. PMID- 7861833 TI - [Intravenous amphotericin B as prevention of deep mycoses in allogeneic bone marrow transplantation]. AB - BACKGROUND: To evaluate the efficacy of i.v. amphotericin B (AmB) as prophylaxis of deep mycosis (DM) in allogenic bone marrow transplantation (BMT). METHODS: From July 1991 to May 1993, 45 consecutive patients treated by allogenic BMT with no previous history of systemic mycosis and with normal renal function were administered prophylactic AmB at a dose of 0.5 mg/kg/48 h from day + 1 BMT until hemoperipheral recovery (group A). These were compared with an historic control group made up of 45 consecutive patients submitted to BMT from January 1990 to June 1991 who did not receive prophylactic AmB (group B). During the neutropenic phase all the patients remained in isolation units with laminar flow of filtered air and were administered oral non absorbable antibiotic therapy and diet of low bacterial content. The incidence of DM and the dose of AmB administered during the first 120 days post BMT were evaluated. RESULTS: In the first 30 days following BMT 3 (7%) cases of DM were observed in group A and 3 (7%) in group B. Four (9%) additional cases were found from days 30 to 120 in group A and 3 (7%) in group B. In 3 (7%) patients of the group which received prophylaxis and in 4 (9%) of the control group Candida spp. was isolated. In 3 (7%) patients from group A and 1 (2%) patient from group B the infection was due to Aspergillus. Although the patients from group A received therapeutic AmB less frequently (78% vs 91%) and later (13 [SD +/- 5.9] vs 9.2 [SD +/- 4.6] days) than those of group B (p < 0.002) the mean dose of AmB per patient treated was similar in both groups (11.3 [SD +/- 8.8] vs 11.8 [SD +/- 7] mg/kg). CONCLUSIONS: The prophylactic use of systemic amphotericin during the neutropenic phase of bone marrow transplantation does not reduce either the incidence of deep mycosis or the mean dose of amphotericin administered. PMID- 7861834 TI - [Effect of social factors on quality of life of survivors of myocardial infarction]. AB - BACKGROUND: The aim of this study was to analyze the effect of the social environment on the quality of life of the survivors of an acute myocardial infarction. METHODS: A prospective cohort study was carried out with telephone follow up of patients admitted in the Intensive Care Units of six public hospitals in the region of Valencia (Spain). Three hundred eighty consecutive patients admitted for acute myocardial infarction were studied being followed a median of 3.4 years. Follow up was complete in 91.6% of the cases. RESULTS: The global quality of life was good. The component most affected was that of physical activity. Following control of the effect of the biologic and health care covariables, the quality of life was inversely and independently associated with age, female sex, low educative level and foreigness. CONCLUSIONS: Unequality was found in regard to the quality of life based on the socioeconomic level of survivors of acute myocardial infarction. PMID- 7861835 TI - [Original articles published in Medicina Clinica during 30 years (1962-1992): number of authors, interval between acceptance and publication and bibliographic references]. AB - BACKGROUND: To study different aspects of original articles published in Medicina Clinica (Barcelona) over a 30-year period (1962-1992), with special emphasis on references. METHODS: We selected 12 articles per year at 5-year intervals (1962, 1967, 1972, 1977, 1982, 1987, 1992) using a systematic sampling procedure. The following variables were assessed: number of authors, interval between acceptance of the manuscript and publication in the journal, total number of references, language, document type, and name of the journal. RESULTS: The mean (+/- standard deviation) number of authors showed a statistically significant increase (ANOVA; F = 13.666; p = 0.0001) from 1.83 +/- 0.71 in 1962 to 6.41 +/- 1.97 in 1992. The interval between acceptance and publication decreased from 315.72 +/- 20.48 days in 1982 to 206.16 +/- 89.23 in 1992 (ANOVA, F = 6.074; p = 0.0058). A total of 1816 references were found (24.2 references per article). English was the language of publication most commonly found (76.76%) followed by Spanish (12.6%). There was a statistically significant increase in the use of references corresponding to English articles over the study period (chi 2 = 314.431; p = 0.0001). A significant change was also observed in the type of document use (chi 2 = 143.996; p = 0.0001); references from journals increased from 73.51% in 1962 to 91.40% in 1992. In addition, 50.46% of the articles were published in only 7.84% of the journals. Eight journals devoted to internal medicine (1.79% of all journals) included 23.46% of the references. CONCLUSIONS: The number of authors has shown a significant increase during the study period. The time elapsed between acceptance and publication has decreased significantly. Spanish authors acquired information mostly from the English literature. Articles published in journals are also mostly used as references. A large percentage of references consisted of articles published in core general journals. These journals accumulate a remarkable percentage of the information. PMID- 7861836 TI - [Gene therapy: new prospects in the treatment of cancer]. PMID- 7861837 TI - [Improvement of hospital quality]. PMID- 7861838 TI - [Disposal of clinical waste: between safety and efficiency]. PMID- 7861839 TI - [Report on radiosurgery. General Subadministration of Management and Evaluation of Health Technology. General Administration of Health Insurance and Planning. Ministry of Health and Utilization, Madrid]. PMID- 7861840 TI - [Treatment and prevention of main infections associated with HIV]. PMID- 7861841 TI - [Apropos of a book review]. PMID- 7861842 TI - [Exacerbation of psoriasis by treatment with alpha interferon]. PMID- 7861843 TI - [Publicity on drugs. Errors of translation: EEC directive and Royal decree]. PMID- 7861844 TI - [Role of sex in myocardial infarct survival]. PMID- 7861845 TI - [Physicians' long working hours are questioned in the USA]. PMID- 7861846 TI - [Health care in Iraq. Severe shortage of drugs and equipment. Caused by the embargo of the UN or by the errors of own politicians?]. PMID- 7861847 TI - [The National Board of Health and Welfare--a messenger of the big hospitals?]. PMID- 7861848 TI - [Interns, time to scream!]. PMID- 7861849 TI - [Drug industry and continuing education II]. PMID- 7861850 TI - [ICD-10 and the emperor's new clothes]. PMID- 7861851 TI - [District nurses' right to prescribe drugs]. PMID- 7861852 TI - [Treatment of otosclerosis--points of view from Finland]. PMID- 7861853 TI - [More women than men die because of myocardial infarction. Is it caused by a specific sex factor or inferior treatment?]. PMID- 7861854 TI - [Thrombolysis is replaced by angioplasty. A change of strategy in the Swedish care of myocardial infarction?]. PMID- 7861855 TI - [No bicycles for children under 6 years of age!]. PMID- 7861856 TI - [The new emergency care is outlined. The proposal of the National Board of Health and Welfare is radical, but without a basis for medical decision making]. PMID- 7861857 TI - [Ovulation stimulation. Use and "abuse"]. PMID- 7861858 TI - [Scopolamine plaster caused hallucination. Toxic psychosis in a 10-year-old boy caused by an agent against motion sickness]. PMID- 7861859 TI - [Herpes simplex--a difficult diagnosis? Varying manifestations are misleading]. PMID- 7861860 TI - [A very serious case of lithium poisoning. Good results with continuous arteriovenous dialysis]. PMID- 7861861 TI - [Coronary angioplasty in acute myocardial infarction. A superior alternative to thrombolytic therapy?]. PMID- 7861862 TI - [Arterial hypoxia is common in colonoscopy. An overlooked risk of heavy intravenous sedation]. PMID- 7861863 TI - [Gastrointestinal microorganisms may cause cancer. Research for a new pharmacological treatment is under way]. PMID- 7861864 TI - [Women's health. With increased education and increased influence women will have more control over their bodies and lives]. PMID- 7861865 TI - [Injuries among young cyclists. The bicycle helmet could be improved]. PMID- 7861866 TI - [Is the helmet campaign an effective way to prevent injuries? Analysis of attitudes among adults and teenagers]. PMID- 7861867 TI - [Bypass surgery is effective also in women]. PMID- 7861868 TI - Lancet conference 1996: cognitive impairment to dementia. PMID- 7861869 TI - Is it "all in the genes"? PMID- 7861870 TI - Comparing antiepileptic drugs. PMID- 7861871 TI - Cholesterol-lowering in infancy? PMID- 7861872 TI - Ethics of n-of-1 trials. PMID- 7861873 TI - Prospective randomised trial in 1062 infants of diet low in saturated fat and cholesterol. AB - Interventions to avoid atherosclerosis might be more successful if launched early in life when eating and life-style patterns are formed, but dietary interventions have been limited by fears of diet-induced growth failure. We investigated the effects of a diet low in saturated fat and cholesterol on serum lipid concentrations and growth in 1062 healthy 7-month-old infants in a randomised study. Every 1-3 months, families in the intervention group received dietary advice aimed at adequate energy supply, with low fat intake (30-35% energy, polyunsaturated/monounsaturated/saturated fatty acid ratio 1/1/1, and cholesterol intake < 200 mg daily). Infants in control families consumed an unrestricted diet. 3-day food records were collected at ages 8 and 13 months. Growth was carefully monitored. Between 7 and 13 months serum cholesterol and non-high density-lipoprotein cholesterol concentrations did not change significantly in the intervention group (mean change -0.03 [SD 0.72] mmol/L and 0.01 [0.67] mmol/L) but increased substantially in the control group (0.24 [0.64] mmol/L and 0.23 [0.60] mmol/L; p for difference in mean changes between groups < 0.001). Daily intakes of energy and saturated fat were lower in the intervention than in the control group at 13 months (4065 [796] vs 4370 [748] kJ, p = 0.033, and 9.3 [3.5] vs 14.5 [4.8] g, p < 0.001, respectively), and intake of polyunsaturated fat was higher (5.8 [2.2] vs 4.4 [1.4] g, p < 0.001). Growth did not differ between the groups and was as expected for children at this age. Serum cholesterol concentrations fell significantly in parents of intervention-group infants. The increases in serum cholesterol and non-high-density-lipoprotein cholesterol concentration that occur in infants between the ages of 7 and 13 months can be avoided by individualised diets, with no effect on the children's growth. PMID- 7861874 TI - Mortality and morbidity from malaria in Gambian children after introduction of an impregnated bednet programme. AB - After the success of a controlled trial of insecticide-treated bednets in lowering child mortality, The Gambia initiated a National Insecticide Impregnated Bednet Programme (NIBP) in 1992 with the objective of introducing this form of malaria control into all large villages in The Gambia. Five areas (population 115,895) were chosen as sentinel sites for evaluation of the NIBP. During the first year of intervention a 25% reduction was achieved in all-cause mortality in children 1-9 years old living in treated villages (rate ratio 0.75 [95% CI 0.57 0.98], p = 0.04). If one area where the programme was ineffective was excluded, the reduction was 38% (0.62 [0.46-0.83), p = 0.001). A decrease in rates of parasitaemia and high-density parasitaemia, an increase in mean packed-cell volume (rate ratio 0.75 [95% CI 0.59-0.98], p = 0.04) and an improvement in the nutritional status of children living in treated villages were also detected. In a country such as The Gambia, where nets were widely used and which has a good primary health care system, it is possible to achieve insecticide-treatment of bednets at a national level with a significant reduction in child mortality; but at a cost which the country cannot afford. PMID- 7861875 TI - Pharyngeal sensation and gag reflex in healthy subjects. AB - The gag reflex is often used in the assessment of swallowing, yet its absence does not predict aspiration in acute stroke. Disordered pharyngeal sensation has been found to be a sensitive predictor. The occurrence of gag reflex and pharyngeal sensation in healthy people is unknown. We studied these tests in 140 healthy subjects (half elderly and half young). Gag reflex was absent in 37% of subjects whereas pharyngeal sensation was absent in only 1. The results largely explain the low predictive value of gag reflex in the assessment of aspiration in acute stroke. Testing pharyngeal sensation would be more likely to be useful in these circumstances. PMID- 7861876 TI - Differentiation of follicular lymphoma cells after autologous bone marrow transplantation and haematopoietic growth factor treatment. AB - A patient with follicular lymphoma developed a striking but transient plasmacytosis in blood and bone marrow with paraproteinaemia after treatment by autologous bone marrow transplantation and interleukin-3 (IL-3). By immunophenotyping, cytogenetics and Southern blotting, we proved that the plasma cells were clonally related to the original lymphoma cells. This event was preceded by fever accompanied by high IL-6 concentrations. The patient recovered spontaneously and had a long-lasting remission. We speculate that the bone marrow derived malignant B cells were stimulated by IL-3 and IL-6 into terminally differentiated plasma cells. PMID- 7861877 TI - Defective maturation and function of antigen-presenting cells in type 1 diabetes. AB - Macrophages and dendritic cells are important as antigen-presenting cells in the islet autoimmune response. We report decreased maturation of dendritic cells from blood monocytes of 61 patients with type 1 diabetes compared with 31 healthy controls (medians 26 and 35%, respectively, p = 0.0005). The dendritic cells also had reduced ability to cluster (96 and 124 clusters, respectively, p = 0.0005), and to stimulate autologous and allogeneic T cells. Because optimum antigen presentation is primarily required for tolerance induction rather than for immunisation, the defective maturation and function of diabetic dendritic cells might be the basis for disturbed activation of regulatory (suppressor) T cells. PMID- 7861878 TI - Accidental hypothermia. PMID- 7861879 TI - Randomised controlled trial of routine individual feedback to improve rationality and reduce numbers of test requests. AB - Feedback can be described as a way to provide information on doctors' performance to enable changes in future behaviour. Feedback is used with the aim of changing test-ordering behaviour. It can lead to reductions in test usage and cost savings. It is not sufficiently clear, however, whether feedback leads to more appropriate test use. Since 1985, the Diagnostic Coordinating Center Maastricht has been giving feedback on diagnostic tests as a routine health care activity to all family doctors in its region. Both quantity and quality of requests are discussed. In a randomised, controlled trial over 2.5 years, discussion of tests not included previously was added to the existing routine feedback. One group of family doctors (n = 39) received feedback on test-group A (electrocardiography, endoscopy, cervical smears, and allergy tests), the other (n = 40) on test-group B (radiographic and ultrasonographic tests). Thus, each group of doctors acted as a control group for the other. Changes in volume and rationality of requests were analysed. The number of requests decreased during the trial (p = 0.036). Request numbers decreased particularly for test-group A (p = 0.04). The proportion of requests that were non-rational decreased more in the intervention than in the control groups (p = 0.009). Rationality improved predominantly for test-group B (p = 0.043). Thus, routine feedback can change the quantity and quality of requests. PMID- 7861880 TI - Risk assessment and factor VIII concentrates. PMID- 7861881 TI - Is Surgeon General's post indispensable? PMID- 7861882 TI - Laboratory models of atherogenesis. PMID- 7861883 TI - Something better than zidovudine for children. PMID- 7861884 TI - Endemic goitre in Guinea. PMID- 7861885 TI - Endemic goitre in Guinea. PMID- 7861886 TI - Management of ventricular fibrillation in commercial airliners. PMID- 7861887 TI - Pelvic exenteration. PMID- 7861888 TI - Clozapine in Parkinson's disease. PMID- 7861889 TI - Drug-licensing anomalies and Parkinson's disease. PMID- 7861890 TI - When does HIV cross the placenta? PMID- 7861891 TI - Electroconvulsive therapy. PMID- 7861892 TI - Electroconvulsive therapy. PMID- 7861893 TI - Electroconvulsive therapy. PMID- 7861894 TI - Evening primrose oil and atopic eczema. PMID- 7861895 TI - Health insurance in rural Africa. PMID- 7861896 TI - Health insurance in rural Africa. PMID- 7861897 TI - Doctors, managers, and health services. PMID- 7861898 TI - Doctors, managers, and health services. PMID- 7861899 TI - Doctors, managers, and health services. PMID- 7861900 TI - Wellcome brain gain. PMID- 7861901 TI - Prevention of male suicides: lessons from Gotland study. PMID- 7861902 TI - Giardiasis in pancreas. PMID- 7861903 TI - Response to specific anti-oestrogen (ICI182780) in tamoxifen-resistant breast cancer. PMID- 7861904 TI - Budd-Chiari syndrome and factor V Leiden mutation. PMID- 7861905 TI - Budd-Chiari syndrome and factor V Leiden mutation. PMID- 7861906 TI - Mutation in coagulation factor V associated with resistance to activated protein C in patients with coronary artery disease. PMID- 7861907 TI - Cytokine secretion after allogeneic or autologous blood transfusion. PMID- 7861908 TI - Does diet or alcohol explain the French paradox? PMID- 7861909 TI - Does diet or alcohol explain the French paradox. PMID- 7861910 TI - Molgramostim to treat SS-sickle cell leg ulcers. PMID- 7861911 TI - Does memory constrain utilization of top-down information in spoken word recognition? Evidence from normal aging. AB - Young and elderly adults heard recorded words that had been computer-edited from connected speech so as to be heard in isolation from their linguistic surround. Word identification was tested for words in isolation and when heard with increasing amounts of linguistic context that had either preceded or followed them in their original utterances. Although the elderly subjects were poorer in identifying the words in isolation compared to young adults, both age groups showed similar increases in correct word identification as increasing amounts of prior context were presented. By contrast, context that followed the target words was less effective for the elderly subjects than it was for the young. It is argued that a memory trace of the unclear stimulus must be maintained for effective utilization of following context in a retrospective analysis. The elderly subjects' relative inability to utilize following context implicates an age-related memory deficit operating at the sentence level. PMID- 7861912 TI - Durational effects in final lengthening, gapping, and contrastive stress. AB - Lengthening in utterance-final position and in contrastive stress was examined in Hebrew, focusing on the distribution of the durational effect across syllables and within the final syllable. Initially-stressed and finally-stressed bisyllabic key words were read in sentence-final versus nonfinal position, and in contrastive stress versus nonstressed constructions. The results were compared with data from an earlier study of verb gapping. Contrastive stress showed a smaller effect than final lengthening and verb gapping, consistent with the claim that other acoustic parameters are more prominently involved in this process. Utterance-final lengthening and verb gapping principally affected the final syllable regardless of stress, whereas contrastive stress primarily lengthened the stressed syllable. The pattern of progressively greater lengthening within the utterance-final syllable, previously found for stressed syllables, applied to unstressed syllables as well. The finding that target syllables in sentence-final position are characterized by progressive lengthening, unlike those in contrastive stress and gapping, supports the suggestion that utterance-final lengthening is a reflection of deceleration at the end of motor activity. Durational measures of individual syllables within the key word, and of segments in addition to the vocalic portion of the final syllable, reveal differences in the acoustic implementation of different lengthening processes. PMID- 7861913 TI - Individual differences in reading subprocesses: relationships between reading ability, lexical access, and eye movement control. AB - This study examines the relationship between individual reading subprocesses and general reading ability in college students. The reading measures included eye movements while reading a passage, lexical decision latencies, comprehension, and vocabulary size. The results indicate that a distinct relation exists between reading speed and fixation behaviour associated with regressions through a text. About half the variability in comprehension scores can be predicted by subjects' performance on nonword lexical decisions, gaze durations, and vocabulary scores. These findings are discussed with reference to past studies using similar reading measures. PMID- 7861914 TI - Evaluation of a multidrug therapy programme of leprosy control. AB - MDT programmes for leprosy control have two objectives, controlling leprosy in populations and controlling leprosy in individuals. Evaluation of such programmes needs to address both objectives and this can be done by a review of the trends in key indicators and by site visits. Site visits are more expensive and should be done less frequently, but they can reveal issues not apparent in routinely produced statistics. Evaluation on an annual basis is the responsibility of programme managers and programme funders. Evaluation by programme staff themselves should be encouraged and supported. Evaluation of an MDT programme's effectiveness in controlling leprosy in a population should be by analysis of case detection as a proxy for incidence. Prevalence rates will continue to be monitored because of the WHO elimination goal, but these do not reflect disease transmission. Case detection is a proxy measure of incidence and depends on consistency in case detection activities. Case detection data by age, gender, mode of detection, disability ratio and lepromatous (MB) rate need to be analysed over at least 5 years and preferably 10 years to give an indication of trends in incidence. Caution is needed, however, as the pattern seen when case detection deteriorates may resemble the pattern expected when transmission is reduced. The site visit is important in this situation in allowing examination of the case detection activities, as well as in looking for new, undetected cases in the population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861915 TI - Will there be a need for leprosy control services in the 21st century? PMID- 7861916 TI - The role of IgM antiphenolic glycolipid-1 antibodies in assessing household contacts of leprosy patients in a low endemic area. AB - This study was carried out to assess the role PGL-1 antibodies may have to play in assisting with early diagnosis in close contacts of leprosy patients. Blood samples were collected from patients and contacts. It was found that 6.9% of index cases and 1% of healthy contacts were positive for PGL-1 antibody. None of the healthy contacts developed clinical leprosy and all had become seronegative at follow-up. We conclude that screening for PGL-1 antibodies has a limited role in the screening of healthy contacts and may not be of use in low endemic areas. PMID- 7861917 TI - Field evaluation of WHO-MDT of fixed duration at ALERT, Ethiopia: the AMFES project--I. MDT course completion, case-holding and another score for disability grading. AB - We report on 286 new leprosy patients (128 PB, 158 MB) enrolled in the AMFES project, a field study in which patients are monitored during WHO-MDT and during 5 years thereafter, by active surveillance. This first paper describes the purposes, organization and methods of the study, patient enrollment and preliminary results of MDT completion and case-holding. Of 128 PB patients 102 (79.7%) completed MDT and of 91 on surveillance for more than 1 year, coverage with reviews had been good or very good for 31, fair or poor for 36 and very poor or nil for 21 PB patients. Of 158 MB patients 64 had completed MDT, and 26/128 (20.3%) PB and 18/158 (11.4%) MB patients were lost to follow-up during treatment, with 76 MB patients still on treatment. At first diagnosis, 159/286 (55.6%) had nerve function impairment, with no significant differences in disability grade by gender or between PB and MB patients. The proportion of disability grade 0 amongst new cases decreased very significantly with age, from 28/41 (68.3%) for age 0-14 years to 13/57 (22.8%) for 50 years and above. In view of the limitations of patient disability grades, a score per patient of the sum of disability grades for the four extremities, named 'HF-impairment score', is shown to be more informative. Incidence of leprosy reactions and neuritis in these patients, during treatment and during surveillance, is reported upon in Part II (on pp. 320-332 of this issue). PMID- 7861918 TI - Field evaluation of WHO-MDT of fixed duration, at ALERT, Ethiopia: the AMFES project--II. Reaction and neuritis during and after MDT in PB and MB leprosy patients. AB - For a cohort of 286 leprosy patients the incidence rates and clinical manifestations of leprosy reactions during treatment and surveillance are described. Currently, individual patients had been observed for up to 4 years. It is intended that surveillance within this project should continue for up to 5 years after treatment. Of 128 PB patients, observed for 267 person-years (mean 2.1) 27 had 35 episodes of reaction, corresponding to an overall incidence rate of 131 events per 1000 person-years-at-risk (pyar). Of 158 MB patients observed for 402 person years (mean 2.5), 64 had 114 reactions, with an overall incidence of 284 events per 1000 pyar. For both PB and MB patients, incidence rates during treatment and post-MDT surveillance were similar. For PB patients, pre-existing physical impairment at the start of MDT was a significant risk factor for the occurrence of subsequent events, but this was not found in MB patients. PMID- 7861919 TI - Field comparison of 10-g and 1-g filaments for the sensory testing of hands in Ethiopian leprosy patients. AB - In ALERT's leprosy control programme sensory testing of hands and feet is done with a nylon filament giving a 10-g stimulus, but doubts arose that early partial sensory loss in hands would not thus be discovered. In order to evaluate the relative performance of 1-g and 10-g filaments for sensory testing on the palms of hands, both filaments were used separately in a series of 1,021 examinations on several consecutive occasions in 159 leprosy patients and 97 nonleprosy controls. The 1-g filament was always felt on normal hands and does not lead to false positive findings of nerve dysfunction. If the 1-g filament were used routinely, almost twice as many instances of 'neuritis' would be discovered and treated, if the criterion for diagnosis and treatment of new nerve dysfunction remained as it is for nerves tested with the 10-g filament. It appears desirable to distinguish between testing for early sensory loss and for loss of protective sensation. The two tests may each need their own instrument and separate recording of the results. PMID- 7861920 TI - Circulation and sensation at the fingertips of claw hands. AB - Measurements of skin blood flow (by laser Doppler flowmetry) and temperature were made under environmental conditions promoting peripheral vasodilatation at the fingertips of a disfigured 'clawed' hand in 12 leprosy patients long-resident at Baba Baghi Leprosy Hospital, Tabriz, Iran. Sensory function was assessed by measuring the responses to light touch, pain and temperature of each finger, and peripheral autonomic function was gauged by estimating palmer sweating and by measuring skin vasomotor reflexes in response to inspiratory gasp. In 2 patients all measured fingers had laser Dopper flux (LDFlux) values and skin temperatures lower than the 95% confidence limits for the mean of 20 healthy controls, i.e. were impaired; in 2 patients all fingers had normal values for LDFlux and temperature; and in 8 patients there was a combination of impairment with most fingers normal for these parameters but with the small finger most commonly impaired. There were 10 (67%) fingers with impaired LDFlux and temperature values who had significant sensory impairment, whereas only 5 (18%) of the fingers with normal LDFlux values and temperatures had a similar sensory deficit. Overall, the fingers with the most impaired sensation had significantly (P < 0.05) lower LDFlux and temperature values than those with no sensory deficit. Microcirculatory impairment was not related to disordered skin vasometer reflexes or dysfunction of sweating. We concluded that the relationship between motor (skeletal muscle) nerve paralysis and any subsequent sensory neuropathy and/or microcirculatory impairment is more complex than might be expected from previous understanding of the disease. PMID- 7861921 TI - Silent neuropathy in leprosy: an epidemiological description. AB - This paper presents epidemiological data on silent nerve function impairment in leprosy based on a retrospective study of 536 patients registered at Green Pastures Hospital, Pokhara, West Nepal. Because of the multiple possible aetiologies it is proposed that the clinical phenomenon should be named 'Silent Neuropathy' (SN). We defined this as sensory or motor impairment without skin signs of reversal reaction or erythema nodosum leprosum (ENL), without evident nerve tenderness and without spontaneous complaints of nerve pain (burning or shooting pain), paraesthesia or numbness. The functioning of the main peripheral nerve trunks known to be affected in leprosy was assessed using a nylon filament to test touch thresholds and a manual voluntary muscle test to quantify muscle strength. Almost 7% of new patients had SN at first examination. The incidence rate of SN among the 336 new patients who were available for follow-up was 4.1 per 100 person years at risk. In total, 75% of all SN episodes diagnosed after the start of chemotherapy occurred during the first year of treatment. During steroid treatment the sensory and motor function in nerves affected by SN improved significantly (p = 0.012, Wilcoxon matched-pairs signed ranks test) over a period of 3 months. The patients with more extensive clinical disease (3/9 or more body areas involved, more than 3 enlarged nerves or a positive skin smear) were found to be at increased risk of developing SN. We discuss 4 different possible aetiologies of SN: 1, Schwann cell pathology; 2, nerve fibrosis; 3, cell mediated immune reaction; and 4, intra-neural ENL. Some epidemiological evidence is presented that suggests that SN cannot be equated with a 'reversal reaction expressing itself in the nerves'. It is recommended that all patients should have a nerve function assessment at every visit to the clinic at least during their first year of treatment. Regular nerve function assessment is essential to detect SN at an early stage and to prevent permanent impairment of nerve function. PMID- 7861922 TI - Social problems of women leprosy patients--a study conducted at 2 urban leprosy centres in Delhi. AB - Leprosy seems to afflict women less commonly than men, but for cultural reasons this difference may be more apparent than real. Unfortunately, the effects are as equally devastating, if not more so, in women than in men. This study, carried out at the Urban Leprosy Centres of Safdarjung Hospital and Dr Ram Manohar Lohia Hospital in Delhi, showed that the impact of stigmata attached to leprosy had more effect on educated women belonging to a higher socioeconomic group than on less fortunate women. Discriminative attitudes were more common in joint than nuclear families. Although many got support from their families, the disease had definite psychological effects. Because of the fear of infecting the family members, women sufferers kept themselves aloof and were constantly worried about divorce. Fear of social ostracism prevented the disclosure of disease to the community. Deformities and disabilities led to a deterioration in their functional capabilities and their psychological state of mind. Pregnancy did not affect regularity of treatment. Many women needed an escort to attend the clinic. Solutions to minimize some problems have been suggested. PMID- 7861923 TI - Integrating leprosy control into primary health care: the experience in Ghana. AB - Integration of leprosy control into primary health care is the most comprehensive and permanent system of delivering care to leprosy patients. But so far only a few countries have adopted this approach, largely on account of a fear of failure. Over the past decade Ghana has developed a model approach towards the transition from a vertical to an integrated programme. The highlights of our approach included the development of the leprosy service as part of the overall development of the health service, increasing capacity building for leprosy control at the district and subdistrict levels as well as the establishment of a regular and effective monitoring to identify and correct operational problems early. This paper describes the principles behind the integration, the strategies adopted and how they were implemented. It also includes the achievements made as well as the problems that were encountered and how they were solved. PMID- 7861924 TI - Advantages, indications, and the manufacturing of melted PVC waterpipe splints. AB - There are several indications when to use splints in the treatment of leprosy. PVC waterpipe is a cheap and easily available material in developing countries. Its advantages, indications, and the manufacturing of splints are described. PMID- 7861925 TI - Analysis of competitive examination in leprosy for medical undergraduates in Bombay over 22 years old. PMID- 7861926 TI - Inoculation of the Mycobacterium leprae into the hamster cheek pouch. PMID- 7861927 TI - Protective footwear for leprosy patients with sole sensory loss or ulceration of the foot. PMID- 7861928 TI - Plantar lesions in tuberculoid leprosy: a report of 3 cases. PMID- 7861929 TI - Comment: reversal reaction in multibacillary leprosy patients following MDT with and without immunotherapy with a candidate for an antileprosy vaccine, Mycobacterium W. H. K. Kar et al. PMID- 7861930 TI - Comment: leprosy control through general health services and/or combined programmes. P. Feenstra. PMID- 7861931 TI - Reply: 'Results of surgical procedures for the correction of foot-drop and lagophthalmus due to leprosy'. PMID- 7861932 TI - beta-Carotene transport in human lipoproteins. Comparisons with a-tocopherol. AB - The purpose of this study was to investigate the temporal relationships of the transport of beta-carotene in human lipoproteins. We administered 60 mg beta carotene with breakfast to nine fasting subjects, then blood samples were collected at intervals of up to 75 h, lipoproteins were isolated, and beta carotene was quantitated. beta-Carotene concentrations in chylomicrons and very low density lipoproteins (VLDL) peaked at 6 and 9 h, respectively. Nonetheless, at all time points the majority of plasma beta-carotene was contained in low density lipoproteins (LDL), while high density lipoproteins (HDL) carried a smaller portion (at 24 h, 73 +/- 8% in LDL as compared with 23 +/- 5% in HDL). In three subjects, transport of beta-carotene was compared with the results of earlier studies on the transport of stereoisomers of alpha-tocopherol. Unlike plasma RRR-alpha-tocopherol concentrations, which are maintained by the preferential incorporation of RRR-alpha-tocopherol into VLDL by the liver, beta carotene increased and decreased in VLDL similarly to SRR-alpha-tocopherol, a stereoisomer whose concentrations are not maintained in plasma. In conclusion, beta-carotene is primarily transported in the plasma in LDL, but its incorporation by the liver into lipoproteins does not appear to be enhanced. PMID- 7861933 TI - Comparison of fatty acid alpha-oxidation by rat hepatocytes and by liver microsomes fortified with NADPH, Fe3+ and phosphate. AB - Rat liver microsomes, when fortified with NADPH, Fe3+ and phosphate, can catalyze the oxidative decarboxylation (alpha-oxidation) of 3-methyl-substituted fatty acids (phytanic and 3-methylheptadecanoic acids) at rates that equal 60-70% of those observed in isolated hepatocytes (Huang, S., Van Veldhoven, P.P., Vanhoutte, F., Parmentier, G., Eyssen, H.J., and Mannaerts, G.P., 1992, Arch. Biochem. Biophys. 296, 214-223). In the present study we set out to identify and compare the products and possible intermediates of alpha-oxidation formed in rat hepatocytes and by rat liver microsomes. In the presence of NADPH, Fe3+ and phosphate, microsomes decarboxylated not only 3-methyl fatty acids but also 2 methyl fatty acids and even straight chain fatty acids. The decarboxylation products of 3-methylheptadecanoic and palmitic acids were purified by high performance liquid chromatography and identified by gas chromatography/mass spectrometry as 2-methylhexadecanoic and pentadecanoic acids, respectively. Inclusion in the incubation mixtures of glutathione plus glutathione peroxidase inhibited decarboxylation by more than 90%, suggesting that a 2-hydroperoxy fatty acid is formed as a possible intermediate. However, we have not yet been able to unequivocally identify this intermediate. Instead, several possible rearrangement metabolites were identified. In isolated rat hepatocytes incubated with 3 methylheptadecanoic acid, the formation of the decarboxylation product, 2 methylhexadecanoic acid, was demonstrated, but no accumulation of putative intermediates or rearrangement products was observed. Our data do not allow us to draw conclusions on whether the reconstituted microsomal system is representative of the cellular alpha-oxidation system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861934 TI - Upregulation of low density lipoprotein receptor activity by tumor necrosis factor, a process independent of tumor necrosis factor-induced lipid synthesis and secretion. AB - It has been shown that tumor necrosis factor (TNF) rapidly upregulates expression of the low density lipoprotein (LDL) receptors on Hep G2 cells and acutely stimulates hepatic lipid synthesis and secretion in vivo. It may thus be possible that TNF-induced expression of LDL receptors is secondary to a decrease in cellular cholesterol content caused by TNF-stimulated lipid secretion. In order to know whether TNF upregulates LDL receptors by depletion of the cellular cholesterol content, the present experiments were designed to study the temporal relationship between TNF-stimulated expression of LDL receptor activity and TNF induced changes in lipid synthesis and secretion in an in vitro setting by using Hep G2 cells (a highly differentiated human hepatoma cell line) as a hepatocyte model. Hep G2 cells were incubated with TNF (usually 2.5 nmol/L) for certain periods, and LDL receptor activity was evaluated by measuring [125I]LDL binding at 4 degrees C; lipid synthesis and secretion were assayed by measuring [3H]glycerol incorporation into triglycerides and phospholipids as well as [14C]acetate incorporation into cholesterol. We found that a 30-h exposure of the cells to TNF was needed for the effect of TNF to be seen on lipid synthesis and secretion as measured by incorporation of [3H]glycerol into triglycerides and phospholipids, whereas TNF rapidly (in several hours) upregulated LDL receptor activity. TNF stimulated triglyceride synthesis, but did not stimulate phospholipid synthesis. On the other hand, TNF stimulated phospholipid secretion, but did not stimulate triglyceride secretion. Exposure of the cells to TNF for 16 or 24 h neither decreased cholesterol synthesis nor stimulated cholesterol secretion as measured by [14C]acetate incorporation into cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861935 TI - Lipid composition of glucose-stimulated pancreatic islets and insulin-secreting tumor cells. AB - The effect of glucose stimulation (25 mM for 5 min) on the phospholipid and neutral lipid composition of isolated pancreatic islets was studied to find out whether there is a change in the mass of potential lipid mediators or modulators of insulin secretion. For comparison, the lipid compositions of homogenates and subcellular fractions from RINm5F insulin-secreting tumor cells and of glucose stimulated streptozotocin/nicotinamide-induced islet cell tumors were analyzed. After separation of the lipid extract into a neutral and an acidic fraction by anion-exchange chromatography, lipids were separated by high-performance thin layer chromatography and quantitated by in situ densitometry of the cupric sulfate-charred bands. In glucose-stimulated islets, the molar percentages of phosphatidic acid (PA) and of phosphatidylinositol were significantly increased (3.1 vs. 4.7 mol% and 8.6 vs. 11.8 mol%), while those of all other phospholipids and neutral lipids, including 1,2-diacylglycerol, were not significantly changed. In stimulated islet cell tumors, an increase of PA was visible in the microsomal fraction, and there was an increase of lysophosphatidylcholine in the mitochondrial fraction. However, in both tumoral tissues, particularly in RINm5F cells, the lipid distribution pattern showed abnormalities which can be regarded as a loss of differentiation and which limit the usefulness of these tissues for the study of the physiological regulation of lipid metabolism during glucose stimulation. In conclusion, the data are in accordance with a role of PA early in stimulus-secretion coupling. The well-known stimulation of phospholipid synthesis in pancreatic islets during glucose-induced insulin secretion does not result in an increase in the total phospholipid mass. PMID- 7861936 TI - Effect of dietary fat on colonic protein kinase C and induction of aberrant crypt foci. AB - A major objective of the present study was to determine whether a high-fat diet affects early events during colon carcinogenesis. Female Sprague-Dawley rats were injected with saline or azoxymethane (20 mg/kg) and fed either a normal (5% corn oil w/w) or a high (5% corn oil and 15% beef tallow w/w) fat diet. To assess the effect of a known tumor-promoting diet on the early events of neoplastic transformation, Study 1 examined the induction and growth of aberrant crypt foci (ACF) as well as of proliferative indices. The total number of ACF were similar in both groups even after 8 wk of dietary treatment; however, ACF with accelerated growth characteristics (> or = 4 crypts/focal lesion) were more prevalent (P < or = 0.05) in the colons of animals fed the high-fat diet. Metaphase arrest cells and 5'-bromo-2'-deoxyuridine labelled cells showed no appreciable response to dietary changes. To determine whether changes in colonic signal transduction pathways represent an early response to dietary modification, Study 2 evaluated the activity of protein kinase C (PKC), proliferative indices and changes in phospholipid fatty acid profiles. In comparison to the normal fat group, the colons of high-fat fed animals exhibited higher (P < or = 0.05) membranes and lower soluble PKC activity; however, proliferation patterns of these colons were not altered. Changes in the membrane lipid composition were minor; however, an increase in the phosphatidylcholine/phosphatidylethanolamine ratio and in 20:4n-6 was noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861937 TI - Linoleic acid uptake by isolated enterocytes: influence of alpha-linolenic acid on absorption. AB - In a previous study we showed that intestinal uptake of alpha-linolenic acid (18:3n-3) was carrier-mediated and we suggested that a plasma membrane fatty acid protein was involved in the transport of long-chain fatty acids. To further test this hypothesis, the mechanism of linoleic acid (18:2n-6) uptake by isolated intestinal cells was examined using a rapid filtration method and 20 mM sodium taurocholate as solubilizing agent. Under these experimental conditions transport of [1-14C]linoleic acid monomers in the concentration range of 2 to 2220 nM was saturable with a Vm of 5.1 +/- 0.6 nmol/mg protein/min and a Km of 183 +/- 7 nM. Experiments carried out in the presence of metabolic inhibitors, such as 2,4 dinitrophenol and antimycin A, suggested that an active, carrier-mediated mechanism was involved in the intestinal uptake of this essential fatty acid. The addition of excess unlabeled linoleic acid to the incubation medium led to a 89% decrease in the uptake of [1-14C]linoleic acid, while D-glucose did not compete for transport into the cell. Other long-chain polyunsaturated fatty acids added to the incubation mixture inhibited linoleic acid uptake by more than 80%. The presence of alpha-linolenic acid (18:3n-3) in the incubation medium caused the competitive inhibition (Ki = 353 nM) of linoleic acid uptake. The data are compatible with the hypothesis that intestinal uptake of both linoleic, and alpha linolenic acid is mediated by a membrane carrier common to long-chain fatty acids. PMID- 7861938 TI - Occurrence of 5c,8c,11c,15t-eicosatetraenoic acid and other unusual polyunsaturated fatty acids in rats fed partially hydrogenated canola oil. AB - Uncommon cis and trans fatty acids can be desaturated and elongated to produce unusual C18 and C20 polyunsaturated fatty acids in animal tissues. In the present study we examined the formation of such metabolites derived from cis and trans isomers of oleic and linoleic acids of partially hydrogenated vegetable oil origin in rats. For two months, adult male rats were fed a partially hydrogenated canola oil diet containing moderately high levels of trans fatty acids (9.6 energy%) and an adequate level of linoleic acid (1.46 energy%). Analysis of the phospholipid (PL) fatty acids of liver, heart, serum and brain showed no new C18 polyunsaturated fatty acids, except for those uncommon 18:2 isomers originating from the diet. However, minor levels (each < 0.3% PL fatty acids) of six unusual C20 polyunsaturated fatty acids were detected in the tissues examined, except in brain PL. Identification of their structures indicated that the dietary 9c,13t 18:2 isomer, which is the major trans polyunsaturated fatty acid in partially hydrogenated vegetable oils, was desaturated and elongated to 5c,8c,11c,15t-20:4, possibly by the same pathway that is operative for linoleic acid. Furthermore, dietary 12c-18:1 was converted to 8c,14c-20:2 and 5c,8c,14c-20:3; dietary 9c,12t 18:2 metabolized to 11c,14t-20:2 and 5c,8c,11c14t-20:4, and dietary 9t,12c to 11t,14c-20:2. These results suggested that of all the possible isomers of oleic and linoleic acids in partially hydrogenated vegetable oils, 12c-18:1, 9c,13t 18:2, 9c,12t-18:2 and 9t,12c-18:2 are the preferred substrates for desaturation and elongation in rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861939 TI - Rat liver chromatin phospholipids. AB - To shed light on the question whether the phospholipids present in chromatin are native or are due to contamination from nuclear membranes, we labeled the phospholipids of isolated nuclei and determined the amount of phospholipids (PL) and PL fatty acid composition in nuclei and chromatin. The hepatocyte nuclei were isolated and radioiodinated by the lactoperoxidase method under saturating and nonsaturating conditions, and the radioactivity associated with chromatin extracted from these nuclei was monitored. Whereas 97% the label was recovered in the nuclear membranes, only 0.08-0.6% was found in chromatin. The PL present in chromatin were relative to the amounts present in the entire nuclei and calculated as percentage of total, phosphatidylethanolamine (10%), phosphatidylserine (22%), phosphatidylinositol (19%) phosphatidylcholine (14%), and sphingomyelin (35%). In sphingomyelin of chromatin-associated PL an enrichment in polyunsaturated fatty acids was seen. The data indicated that the PL found in isolated chromatin do not seem to be due to contamination from the nuclear membrane. PMID- 7861940 TI - Preparation of defined molecular species of lactosylceramide by chemical deacylation and reacylation with N-succinimidyl fatty acid esters. AB - A procedure for the preparation of specific molecular species of D-erythro lactosylceramide involving deacylation and reacylation of lactosylceramide prepared from bovine brain gangliosides is described. Lactosylceramide was N deacylated by alkaline hydrolysis and the resulting four lysolactosylceramides, which contained d18:1, d20:1, d18:0 and d20:0 long-chain bases, were simultaneously re-N-acylated with the N-succinimidyl ester of either 16:0, 18:0, 20:0, 22:0, 24:0, 20:1, 22:1 or 24:1 fatty acid. The resulting lactosylceramide contained four molecular species of lactosylceramides, i.e., d18:1, d20:1, d18:0 and d20:0 long-chain bases coupled with the fatty acid that was introduced. Lactosylceramides prepared in this manner were separated into four individual molecular species by high-performance liquid chromatography (HPLC). Each of the purified molecular species of lactosylceramide was quantitated by HPLC after derivatization with benzoylchloride and was characterized by mass spectrometry. The yields of reacylated lactosylceramide were 38-58% relative to the starting lactosylceramide; the purity of each of the molecular species of lactosylceramide was greater than 95%. PMID- 7861941 TI - Apolipoprotein A-I, A-IV and E synthesis in the liver of copper-deficient rats. AB - Copper deficiency induces hypercholesterolemia in the rat. This hypercholesterolemia is mainly due to an increase in apo E-rich high density lipoproteins (HDL1). The present study was undertaken to determine whether the HDL increase could be explained by altered low-molecular weight apolipoprotein (apo) synthesis in the liver. The effect of copper deficiency on apo A-I, apo A IV and apo E concentrations in plasma, as well as on respective mRNA levels and synthesis in the liver, were therefore investigated. We observed that the increased HDL1 levels in the plasma of copper-deficient rats were associated with a significant rise in plasma apo E concentrations; however, plasma apo A-I and apo A-IV concentrations remained unchanged. Liver apo synthesis and respective apo mRNA levels were not significantly altered in copper-deficient animals when compared to control rats. No changes in apo E mRNA levels in various tissues from copper-deficient, as compared to control rats, were noted. Based on the data obtained, it was concluded that the observed changes in plasma lipoprotein and apo concentrations are not related to changes in low-molecular weight apo synthesis in the liver. The mechanisms of the impaired catabolism of HDL1 should be further evaluated to possibly explain the observed increase in this fraction in copper-deficient rats. PMID- 7861942 TI - Alkyl glycerol monoethers in the marine sponge Desmapsamma anchorata. AB - 1-O-Hexadecylglycerol (chimyl alcohol), 1-O-heptadecylglycerol and 1-O octadecylglycerol (batyl alcohol) have been identified as the major native constituents of a mixture of free alkyl glycerol ethers isolated from the contained water and the methanolic extract of the sponge Desmapsamma anchorata. Minor components were the free C14, C15, C19, C20 and C21 alkyl glycerol monoethers. The alkyl glycerol monoethers were analyzed and identified by gas chromatography/mass spectrometry of their isopropylidene derivatives. This is the first report on the occurrence of free C15, C19, C20 and C21 alkyl glycerol monoethers in a sponge. PMID- 7861943 TI - [Neuroleptic malignant syndrome. Case reports]. AB - Neuroleptic malignant syndrome is a serious adverse reaction of neuroleptic drug therapy, composed of mental status changes, muscular rigidity, hyperthermia, signs of autonomic instability and typical laboratory findings. The syndrome has received increased attention in the scientific literature since 1980; nevertheless some weighty issues regarding clinical symptoms, etiopathogenesis and treatment require additional studies. This paper presents 9 cases of neuroleptic malignant syndrome prospectively observed in 8 inpatients and 1 outpatient with different psychiatric diagnosis. Levenson's diagnostic criteria were fulfilled in 7 cases; the remaining two had slighter symptoms. So neuroleptic malignant syndrome is to be considered a rare but not unusual side effect of neuroleptics. The risk of syndrome doesn't seem to be correlated with chemical class, D2 receptor affinity and total dosage of neuroleptics; a key factor seems instead to be a quick loading rate of neuroleptics. Seven of 9 cases displayed severe changes in mental status (clouding of consciousness that varies from stupor to coma), violent psychomotor excitement and aggressiveness before the onset of the syndrome. Such clinical features seem themselves, in our experience, to be potential risk factors besides reason for an increase of neuroleptic dosage. Neuroleptic malignant syndrome usually is preceded by prodromal signs, the most important appearing the worsening of alterations in consciousness. Symptoms of neuroleptic malignant syndrome usually appear abruptly and in some cases with a dramatic course; they last, in cases with favourable outcome, a few days to two weeks from neuroleptic withdrawal; by far the worst outcome, instead, occurs if diagnosis and drug discontinuation are not carried out early. The first measure in the treatment of neuroleptic malignant syndrome consists of prompt discontinuation of all neuroleptic medications and other psychopharmacological cures, except for benzodiazepines, and institution of supportive therapy; such interventions can resolve the most of cases. Three patients treated with bromocriptine and/or dantrolene didn't display a different duration of clinical symptoms and rate of complications if compared to patients treated with supportive therapy only. Use of bromocriptine or dantrolene, or both, therefore should be considered as a second line of action. In four cases, neuroleptics were reintroduced within few days of recovery; low potency neuroleptics were employed, given low doses which gradually increased: in none of the 4 cases did the patients experience partial or complete recurrence of neuroleptic malignant syndrome. PMID- 7861944 TI - [Cognitive functioning in adolescent depression]. AB - In childhood and adolescent depression, the interaction between cognitive and emotional disorders is particularly evident: intellectual dysfunctioning often accompanies and integrates the clinical symptomatology. The studies on cognitive functioning have focused their attention on basic cognitive abilities; relatively fewer studies have analyzed other dimensions, such as logical reasoning. Furthermore, most studies have compared depressed patients to normal controls; this methodology tends to obscure the specific effect depression may have on cognitive functioning. The aim of our study is to analyze whether specific patterns of cognitive organization underlie adolescent depressive disorders. Cognitive functioning was assessed both with psychometric tests (WISC-R) and Piagetian logical reasoning tasks (Longeot Logical Thought Scale). The performance of depressed adolescents was compared to that of neurotic patients without depressive symptomatology. To evaluate the course of cognitive organization in relation to depressive symptomatology, some of our patients were studied in follow-up. Thirty-eight adolescents admitted to our Institute participated in the study. The experimental group consisted of 24 depressed adolescents; sixteen subjects were classified as neurotic depressives, eight were diagnosed as depressive personality disorder. The control group consisted of 14 subjects diagnosed as neurotic without depression. At the WISC-R the performance of depressed and controls adolescents were compared in: Full Scale IQ, Verbal and Performance IQ, Verbal-Performance discrepancy; single subtest scores; Bannatyne's four categories. Statistical analyses did not yield any significant differences between groups for any of the WISC-R measures. At the Logical Thought Scale Full Scale scores of the experimental group were significantly lower than controls'.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861945 TI - [Evaluation of therapeutic efficacy and pharmacokinetics of controlled release of trazodone in patients with major depressive disorder]. AB - In the present study, the antidepressant efficacy of a controlled-release (CR) formulation of trazodone was evaluated in 18 depressed patients treated with 150 mg (no. = 10) or 75 mg (no. = 8) nocte doses of the drug for 7 weeks, according to an open design. Drug plasma levels were evaluated on days 7, 14, 28 and 35 of treatment. Moreover, at the end of treatment, the plasma concentration-time curve of the CR trazodone was assessed. CR trazodone was effective in improving depressive and anxious symptomatology as well as in ameliorating the quality of sleep in 13 patients with a low incidence of side effects. Nonresponder subjects had morning plasma levels of trazodone below the value of 650 ng/ml. The pharmacokinetic profile of CR trazodone, observed after 35 days of treatment, may account for both the low occurrence of untoward side effects and the therapeutic efficacy of the single dose at nighttime. PMID- 7861946 TI - [The role of consultation-liaison psychiatry in neuro-motor rehabilitation]. PMID- 7861947 TI - [Premenstrual syndrome: review of literature]. AB - This is a comprehensive review of recent studies on premenstrual syndrome. The specific purpose of the present paper was to update major premenstrual syndrome related research/clinical issues in the following areas: nosographic validity, diagnostic reliability, clinical assessment, psychobiology, treatment progress. Increasing consensus has addressed the development of both performant assessment instruments and prospective clinical studies as well as careful psychobiologic investigation of the affective disorders/premenstrual syndrome crossroad as valuable directions for future studies. Such a research perspective is discussed in the light of the author's previous work in the field. PMID- 7861948 TI - [Psychological dynamics in adolescence regarding death and suicide]. AB - The authors try to analyse the idea of death and suicide in the adolescent and in order to face the psychological dynamics underlying these experiences. Therefore the differences between adolescential vitality and the separation-loss feelings emerge, between the need for autonomy and the search for identification patterns that are peculiar to this part of vital cycle. The autonomy and freedom search seems to pass delusively through the manipulation of the idea of death, to face a theme reserved to adults gives adolescent omnipotence feelings, assuring him at the same time against anguish. In the second part the authors report the clinical case of a boy who attempted suicide turce and who is under observation in the Department of Mental Health. PMID- 7861949 TI - Role of toxins A and B in the pathogenesis of Clostridium difficile disease. PMID- 7861950 TI - Presence of F-like OriT base-pair sequence on the virulence plasmids of Salmonella serovars Gallinarum, Enteritidis, and Typhimurium, but absent in those of Choleraesuis and Dublin. AB - The 90 kb virulence plasmids of Salmonella biosers Gallinarum and Pullorum (expressed as serovar Gallinarum) are non-conjugative. They were, however, found to be readily mobilized by IncFI and IncFIV plasmids, but not by conjugative IncA, IncB = C, IncH, IncL and IncM R plasmids. No virulence plasmids of serovars Choleraesuis, Dublin, Enteritidis, and Typhimurium were mobilized by any of these conjugative plasmids. The 90 kb virulence plasmid of Gallinarum was shown to hybridize to the Tra genes region of IncFI and IncFIV plasmids, suggesting it contains some F Tra genes region. It also hybridized with 75% homology to the virulence plasmid of Typhimurium, and, in decreasing order, to those of Dublin, Enteritidis, and Choleraesuis. A probe made of 319 basepairs of the F OriT region hybridized with approximately 45% homology to the virulence plasmid of Gallinarum, 63% to that of Typhimurium and 50% to that of Enteritidis. The probe, however, failed to hybridize to the plasmid DNAs of IncA, IncB = C, IncH, IncL and IncM, and to the virulence plasmids of Choleraesuis and Dublin. PMID- 7861951 TI - Cloning, characterization and construction of htrA and htrA-like mutants of Brucella abortus and their survival in BALB/c mice. AB - A genomic library of Brucella abortus S2308 was screened for expression of recombinant proteins recognized by sera from mice and from cattle infected with B. abortus. A positive clone, BA1, expressing a 50 kDa peptide was recognized by both sera. Plasmid pBA1, isolated from BA1, was shown by restriction enzyme digestion to possess a 1.9 kb insert. The nucleotide sequence of the pBA1 insert revealed an open reading frame with of 1539 bases with a coding capacity of 513 amino acids and a predicted molecular weight of 50,992. The predicted amino acid sequence showed 37% identity to E. coli HtrA, a temperature inducible serine protease. A second B. abortus htrA gene, designated htrA-like, was identified on a different cloned fragment that also encoded B. abortus recA. The nucleotide sequence of the htrA-like gene revealed an open reading frame of 1422 nucleotides with a coding capacity of 474 amino acids and a predicted molecular weight of 50,155. The deduced amino acid sequence of the htrA-like gene showed 42% and 36% identity with B. abortus and E. coli HtrAs respectively. Western blotting of E. coli lysate containing the htrA-like gene was not recognized by sera from B. abortus-infected cattle or mice. B. abortus htrA but not htrA-like relieved the temperature sensitive phenotype and permitted growth of an E. coli htrA mutant at 42 degrees C. B. abortus htrA and htrA-like mutants were constructed and their survival and growth in BALB/c mice was compared to the parental strain S2308.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7861952 TI - Protein tyrosine kinase inhibitors block the entries of Listeria monocytogenes and Listeria ivanovii into epithelial cells. AB - The internalization of Listeria by intestinal epithelial cells is still poorly understood, however it is becoming apparent that microorganisms have developed the ability to interact with host cell receptor molecules to induce their own internalization. In this report we show that inhibition of cell tyrosine phosphorylation by protein tyrosine kinase (PTK) inhibitors blocks L. monocytogenes entry into both finite and immortalized intestinal cell lines. Some differences were observed between the Listeria species. L. monocytogenes entry was inhibited by between 10- to 100-fold by PTK inhibitors competing with the tyrosine residue binding of the kinase as erbstatin or by PTK inhibitors competing with the binding of ATP to the enzyme as genistein and some tyrphostins. On the other hand, L. ivanovii entry was inhibited by erbstatin as observed with L. monocytogenes but poorly by genistein and tyrphostins. The use of these several PTK inhibitors shows that even though both L. monocytogenes and L. ivanovii entered intestinal and other cell lines by stimulating PTK, it seems that L. monocytogenes stimulated a different PTK than L. ivanovii. According to the fact that the number of PTK receptors increases on immortalized cells, the higher L. monocytogenes internalization observed with immortalized cell lines could be related to a higher PTK receptor number on these cells compared to finite cell lines. PMID- 7861953 TI - Phosphatase-negative mutants of Legionella pneumophila and their behavior in mammalian cell infection. AB - Microbial phosphatases are known or suspected to play a role in the pathogenesis of several intracellular pathogens, including Legionella micdadei. Legionella pneumophila also possess phosphatase activities, but their possible roles in cellular infection are unknown. We generated mutants of a serogroup 1 isolate of L. pneumophila that lack the major phosphatase. Isolation of a Pho- mutant after random mutagenesis with transposon MudII4041 allowed us to dissociate the major alkaline phosphatase (pH optimum approximately 8) from a minor acid phosphatase activity. Both activities were concentrated in the bacterial periplasm. The gene encoding the major alkaline phosphatase (pho) was cloned by expression in E. coli and used to generate a site directed mutation in two L. pneumophila strains. Each parent-mutant pair was compared in a U937 cell tissue culture assay for capacity to infect, lyse, and grow within mammalian cells. Although the parental stains differed in their U937 cell cytopathicity, neither was significantly more infective than its Pho- derivative, suggesting that the alkaline phosphatase activity is not essential for cellular infection. Because they are not attenuated, Pho- mutants can be used to generate gene fusions with E. coli alkaline phosphatase to study and secretion and cellular infectivity in L. pneumophila. PMID- 7861954 TI - Specific binding of Streptococcus pneumoniae to two receptor saccharide structures. AB - Specific binding of Streptococcus pneumoniae to two proposed receptor structures was studied in a solid-phase assay. The assay was based on immunodetection of the pneumococci adhering to the receptors coated to microtiter plates. Non-specific binding owing to hydrophobic forces to uncoated wells could be abolished by treatment of the plates with a blocking buffer. Binding of the pneumococcal cells was demonstrated with the glycolipid asialo-GM1 as receptor with a previously suggested specificity for the disaccharide GalNAc beta 1-4Gal. A non-capsulated mutant bound with high efficiency to this receptor. Two capsulated strains also bound well, but with lower efficiency. Binding of the non-capsulated strain was also demonstrated with lactotriaosylceramide as receptor with a suggested specificity for the disaccharide GlcNAc beta 1-3Gal. The binding assay enables the comparison of the adherence of different strains to purified receptor molecules. PMID- 7861955 TI - The fibronectin binding domain of the Sfb protein adhesin of Streptococcus pyogenes occurs in many group A streptococci and does not cross-react with heart myosin. AB - Sfb protein, a fibronectin binding adhesin of Streptococcus pyogenes (Lancefield group A streptococcus), mediates streptococcal adherence to human epithelial cells via its fibronectin binding domain coded by a repetitive gene region named fnbr. In the present study, Southern blot analysis using the fnbr gene region as a probe to screen genomic DNA from 51 epidemiologically unrelated clinical isolates of S. pyogenes revealed that 70% carried a sequence homologous to the fnbr probe. Among ten other streptococcal strains belonging to serological groups B, C, and G, DNA from only two human S. equisimilis (group C) strains reacted with the probe. Further analysis by PCR-mediated amplification of the binding repeat coding sequences revealed that repeats of different S. pyogenes isolates were identical in size but varied in number, ranging from one to five. Most of the isolates were shown to carry multiple repeats. Presence of the probe-positive sequence correlated strongly with streptococcal binding to purified fibronectin and adherence to HEp2 human epithelial cells; of the 36 probe-positive isolates, 95% bound fibronectin and 89% adhered strongly to epithelial cells, whereas among the 15 probe-negative isolates only 27% had binding activities for fibronectin and 27% showed strong adherence to HEp2 cells. Antibodies raised against the fibronectin binding domain of Sfb protein recognized streptococcal fibronectin binding surface proteins in most of the clinical isolates but did not react with heart or skeletal muscle myosin in an enzyme immunoassay, as is the case with antibodies directed to M protein, another major surface protein of group A streptococci. The results of the present study suggest that Sfb protein could be a potential candidate for a streptococcal vaccine. PMID- 7861956 TI - Characterization of the antiphagocytic activity of equine fibrinogen for Streptococcus equi subsp. equi. AB - The antiphagocytic property of equine fibrinogen for Streptococcus equi subsp. equi strain CF32 was examined in vitro. The results of bactericidal assays demonstrated that the presence of fibrinogen enhanced the ability of overnight and early log-phase cultures of strain CF32 to resist killing by equine neutrophils by 12-fold and seven-fold, respectively (p > 0.01). In addition, fibrinogen-coated bacteria treated with fibrinogen specific F(ab')2 fragments were 32% more susceptible to killing by equine neutrophils after opsonization in serum (p > 0.05), indicating that specific epitopes on fibrinogen may be important for its antiphagocytic effect. Since complement deposition is inhibited on subsp. equi (Boschwitz JS, Timoney JF, Infect Immun 1994; 42, 3515-20, we examined the effect of fibrinogen on complement deposition by using colloidal gold labeling of surface-bound C3. No significant differences were detected in the quantity of C3 deposited on the cell surface after opsonization with serum, serum plus fibrinogen, or plasma. These results suggest that the antiphagocytic property of fibrinogen is not related to the inhibition of complement deposition on the bacterial surface. Pretreatment of CF32 with M protein specific antibody inhibited fibrinogen binding by 72%, and a strain of subsp. equi expressing low levels of M protein bound 64% less fibrinogen than CF32, suggesting that the some of the fibrinogen deposited on the surface of subsp. equi is bound to M protein. PMID- 7861957 TI - Detection of Mycoplasma fermentans DNA from lymph nodes of acquired immunodeficiency syndrome patients. AB - Biopsy samples from seven patients with acquired immunodeficiency syndrome were screened for Mycoplasma fermentans, M. pneumoniae and M. genitalium infection by the polymerase chain reaction. M. fermentans DNA was detected in four patients. Various tissues were evaluated and the mycoplasma were mainly detected from lymph nodes. Moreover, mycoplasma genus-specific DNA was isolated from peripheral blood mononuclear cells of asymptomatic human immunodeficiency virus(HIV)-infected individuals (two of 31 HIV-infected individuals). These data suggest that mycoplasma infection in AIDS patients is not uncommon. PMID- 7861958 TI - A 53 kDa protein of Vibrio cholerae classical strain 0395 involved in intestinal colonization. AB - Mutants of Vibrio cholerae 01 strain 0395 (classical) mutated in genes encoding secretory or cell surface proteins were induced by TnphoA mutagenesis and were selected as blue colonies on L-agar plates containing 5-bromo-4-chloro-3-indolyl phosphate. Southern analysis of the total DNA from blue colonies showed that all mutants had TnphoA insertion in genomic DNA. These mutants were analysed for adherence, colonization and protein profile. Adherence to freshly isolated rabbit intestinal discs was affected in some mutants. The less adhesive mutants were examined for colonization of the intestine of infant mice. One mutant, designated T-87, was extremely poor at colonization and less diarrhaegenic than the parent strain. Analysis of T-87 by SDS-PAGE revealed that two proteins of 53 and 38 kDa were lacking. The 38 kDa protein was identified as OmpU. The 53 kDa protein was extracellular and cells treated with anti-53-kDa antibodies could not colonize the gut of infant mice. The expression of the 53 and 38 kDa proteins in T-87 was dependent of the growth medium. The data suggest that T-87 is mutated in a regulatory gene which regulates the expression of proteins involved in intestinal colonization. PMID- 7861959 TI - Effect of pap copy number and receptor specificity on virulence of fimbriated Escherichia coli in a murine urinary tract colonization model. AB - Escherichia coli FN506 containing pap genes that encode two different P fimbriae adherence specificity types were tested for virulence in a murine urinary colonization model. Strains containing adherence genes on either high copy or low copy plasmids were compared. Bacteria that harbored the adherence genes on high copy plasmids colonized mouse kidneys less well than bacteria with the same adherence genes in low copy even though the high copy strains exhibited greater hemagglutination capacity. Bacteria with either type of P fimbriae were able to colonize but pap-2+ bacteria showed increased colonizing capacity when strains containing pap-1 or pap-2 genes on low copy plasmids were compared. Bacteria containing plasmids with both adherence specificities had a similar colonizing capacity as bacteria with either type separately. PMID- 7861960 TI - Nucleotide sequence variations within the lipopolysaccharide biosynthesis gene gseA (Kdo transferase) among the Chlamydia trachomatis serovars. AB - The gene gseA, involved in the expression of the genus-specific epitope of chlamydial lipopolysaccharide (LPS), was analyzed by temperature gradient gel electrophoresis (TGGE) to visualize nucleotide sequence variations among the 15 serovars of Chlamydia trachomatis. Sequence analysis showed that the TGGE melting profile patterns were able to detect single nucleotide variations within gseA and allowed the arrangement of the serovars in groups of both identical nucleotide sequences and sequences containing identical sites of nucleotide substitutions. Compared to serovar L2, four types of patterns were obtained: (i) serotypes A and Ba; (ii) B and C (causing endemic trachoma); (iii) D through K (causing sexually transmitted oculo-genital infections); (iv) L1 through L3 (the causative agents of lymphogranuloma venereum). A total of 58 isolated of C. trachomatis of genital or conjunctival origin were tested by this method in comparison to reference strains. Forty-eight isolates (13 of type E, 16 of type F, nine of type G, and ten of type K) yielded the same melting profile as the corresponding type strain, independent of whether they were isolated from genital or ocular infections. However, ten B serotype strains of genital origin behaved in TGGE like a typical genital strain and not a trachoma strain. Thus, although gseA was found to be highly conserved among C. trachomatis, the obtained TGGE profiles of the tested strains tended to correlate with their specific site of infection. PMID- 7861961 TI - Dissociation of intact cells from tumors and normal tissues. PMID- 7861962 TI - Intracellular ionized calcium. PMID- 7861963 TI - Assays of cell viability: discrimination of cells dying by apoptosis. PMID- 7861964 TI - High-resolution analysis of nuclear DNA employing the fluorochrome DAPI. PMID- 7861965 TI - DNA analysis from paraffin-embedded blocks. PMID- 7861966 TI - Controls, standards, and histogram interpretation in DNA flow cytometry. PMID- 7861967 TI - DNA content histogram and cell-cycle analysis. PMID- 7861968 TI - Immunochemical quantitation of bromodeoxyuridine: application to cell-cycle kinetics. AB - We have described several laboratory procedures for the immunochemical staining of the halopyrimidines, BrdUrd and IdUrd, in cell suspensions for flow cytometry and a method for staining histological sections on slides. Halogenated pyrimidine quantitation allows cell-cycle parameters, including total cell-cycle time, phase durations, and growth fraction to be determined. We have presented some flow cytometric data to demonstrate the use of these methods in determining bivariate BrdUrd/DNA histograms with CHO cells and in kinetic studies with the brown Norway rat myeloid leukemia model. PMID- 7861969 TI - Application and detection of IdUrd and CldUrd as two independent cell-cycle markers. PMID- 7861970 TI - Detection of BrdUrd-labeled cells by differential fluorescence analysis of DNA fluorochromes: pulse-chase and continuous labeling methods. PMID- 7861971 TI - Light scatter of isolated cell nuclei as a parameter discriminating the cell cycle subcompartments. PMID- 7861972 TI - Cell preparation for the identification of leukocytes. PMID- 7861973 TI - Analysis of DNA content and cyclin protein expression in studies of DNA ploidy, growth fraction, lymphocyte stimulation, and the cell cycle. PMID- 7861974 TI - Oxidative product formation analysis by flow cytometry. PMID- 7861975 TI - Flow cytometric determination of cysteine and serine proteinase activities in living cells with rhodamine 110 substrates. PMID- 7861976 TI - Leucine aminopeptidase activity by flow cytometry. PMID- 7861977 TI - Enzyme kinetics. PMID- 7861978 TI - On-line flow cytometry: a versatile method for kinetic measurements. PMID- 7861979 TI - Detection of intracellular virus and viral products. PMID- 7861980 TI - Multiparameter analysis of leukocytes by flow cytometry. AB - The flow cytometry described can be performed using a single laser. Each laboratory has to establish its own experience base and standard operating procedures. The intent of this discussion has been to illustrate the procedures that will lead to good flow cytometry data acquisition and analysis and to illustrate problematic areas. The most important rule of all is to recognize when there is a problem. It is hoped the information provided herein will be of help in the recognition process. PMID- 7861981 TI - Simultaneous DNA content and cell-surface immunofluorescence analysis. PMID- 7861982 TI - Characterization of nuclear factors involved in 202 gene induction by IFN-alpha, viruses or dsRNA in murine leukemia cells. AB - When treated with IFN-alpha, L1210 leukemia cells express high levels of the mouse 202 gene mRNA after a few hours. Three tandem copies of a 43 bp fragment (GAbox) homologous to the IFN-stimulatable response element (ISRE), located in the 5'-flanking region of the 202 gene, were linked to the reporter CAT gene and transiently transfected into L1210 cells. The data suggest that the GA box is sufficient to confer transcriptional inducibility upon IFN stimulation. Binding assays, using the labeled GA box as a probe, demonstrated the presence of a retarded complex, designated GAbfl, in the nuclear extracts of L1210 cells treated with IFN-alpha. This complex is absent in the extracts of L1210 cells treated with ssRNA viruses or synthetic dsRNA. Moreover, photoaffinity cross linking experiments revealed that GAbfl contains a protein of about 50 kDa. Altogether these results demonstrate that antiviral state induction by IFN-alpha in L1210 cells is preceded by GAbfl binding to the ISRE of the IFN-inducible genes. PMID- 7861983 TI - Systemic infection with Herpes bovis virus 2 evokes a biphasic immune response in the mouse. AB - We evaluated the effects of systemic infection by Herpes bovis virus 2 (HBV-2) on a murine experimental system. We provide evidence that such infection is lethal for the immunocompromised but not for the immunocompetent mouse in which a biphasic immune response is elicited. In particular, 1 day post-infection, we observed a rapid transient depression induced by the virus, as documented by a decrease in peripheral leukocyte counts, mitogenic spleen cell response and resistance to a secondary microbial challenge. Later, HBV-2 infection boosted cytokine secretion and enhanced antimicrobial and antitumoral activities by the splenic district. In conclusion, our experimental model discloses some immunological aspects underlying the complex host-virus interaction. PMID- 7861984 TI - Molecular cloning of Chlamydia trachomatis 26K protein expressed in Escherichia coli. AB - Molecular genetics appears to be the most promising approach to understanding the biology and pathology of Chlamydia. This report focuses on the cloning and the protein expression of a DNA fragment from Chlamydia trachomatis DK20 chromosome. Results of hybridization experiments suggest that this sequence is specifically present within chlamydial DNA. The coding capacity of this DNA fragment is supported by the expression of a 26,000 m.w. peptide, in an Escherichia coli maxicell system. PMID- 7861985 TI - Adhesion of mucoid uropathogenic strains of Pseudomonas aeruginosa to HEp-2 cells. AB - We studied a pili-independent adhesion mechanism to HEp-2 cells present in mucoid uropathogenic strains of Pseudomonas aeruginosa. Our data demonstrate that bacterial adhesion to HEp-2 cell surfaces is time dependent and that the phenotypes involved are influenced by bacterial growth conditions. Sonicated bacterial extracts competitively inhibit the adherence of homologous strains to HEp-2 cells. Adhesins that are heat and trypsin sensitive are located on the surface of the bacterial outer membrane. Immunogenic 55 kDa surface protein is required for the adherence to HEp-2 cell surfaces of non-piliated mucosal uropathogenic P. aeruginosa strains. PMID- 7861986 TI - Effects of continuous exposure to ciprofloxacin on the outer membrane of P. aeruginosa. AB - The present work evaluated the effect of ciprofloxacin on the outer membrane proteins (OMPs), lipopolysaccharide (LPS) and the variation of minimal inhibitory concentrations (M.I.C.) of three P. aeruginosa strains after using 1/2 and 1/16 sub-M.I.C. drug doses for five days. Ciprofloxacin significantly modified the M.I.C. values. After contact with sub-M.I.C. drug doses two strains showed a decreased expression of a band migrating at 46 Kd, i.e. in the region of protein D that some authors claim is involved in quinolone diffusion. No major alteration of LPS structure was observed. PMID- 7861987 TI - Investigation on several phenotypic features in two strains of Mycobacterium genavense. AB - The newly recognized species Mycobacterium genavense causes disseminated infections in AIDS patients, but its prevalence is difficult to assess because of its inability to grow on standard solid media. For the same reason, very little is known about the phenotypic traits of its isolates. We report here the results of our studies on two such strains isolated from AIDS patients and subcultured on a non-standard solid medium. Besides several features conventionally explored for mycobacterial speciation, we tested the isolates for 19 enzymatic activities and determined their mycolic acids profiles by means of high performance liquid chromatography. We also compare our findings with the scanty literature data on the laboratory characteristic and antimicrobial susceptibility of M. genavense. PMID- 7861988 TI - Evaluation of a commercial ELISA kit for the serological diagnosis of Helicobacter pylori infection. AB - H. pylori infection can be diagnosed serologically. We evaluated an ELISA kit (Helicobacter pylori IgG, DIESSE) prepared using a glycine extract of an autoctonous H. pylori strain which produced the highest biologically active urease titre out of five strains tested. The kit was tested with serum samples from H. pylori-infected and uninfected adults and children. The Western Blot technique was used as reference method for the H. pylori infective status. Based on the results obtained by immunoblotting with serum samples from H. pylori negative subjects, two different cut-off values were considered for adults and children. Sensitivity and specificity were respectively 95% and 100% for adults, 95.6% and 97.8% for children. In conclusion, the clinical accuracy of this commercially available ELISA kit proved to be very good; the adoption of two different cut-off values for adults and children also improved its parameters of reliability. PMID- 7861989 TI - Characterization of the plasmid pVS809 from Bifidobacterium globosum. AB - A plasmid from a B. globosum strain was cut with 38 restriction enzymes and a physical map was constructed. Out of a total of 121 clones from curing experiments, plasmid was lost in 58% and 100% for acridine orange and ethidium bromide curing agent respectively. The plasmid does not exist as a chromosomal integrated form. An attempt to determine phenotypic characters encoded by the plasmid was made by electrophoretic analyses of the total proteins. PMID- 7861990 TI - Isolation of Borrelia burgdorferi in Tuscany (Italy). AB - To evaluate the diffusion of Borrelia burgdorferi in Tuscani (Italy) 720 ticks were collected and subsequently cultured for Borrelia burgdorferi. A strain of Borrelia burgdoferi was isolated from one tick; this being the first such reported identification in Central-Southern Italy. PMID- 7861991 TI - Netilmicin influences siderophores production and iron receptor expression in Escherichia coli. AB - This study investigated the effect of subinhibitory concentrations of netilmicin on the phenolate (enterochelin), hydroxamate (aerobactin) and total siderophores production and on the 81-kDa and 74-kDa receptors expression in Escherichia coli. Netilmicin at 1/40 MIC reduces total siderophores by 40%; the cathecols by 50% and the hydroxamate by 80%. Concomitant with siderophores reduction, the antibiotic induces the upregulation of the 81-kDa protein receptor. Both effects reduce the ability of the bacterium to survive in the host. PMID- 7861992 TI - The propagation of a porcine hemagglutinating encephalomyelitis virus in swine kidney cell cultures. AB - An established cell line, KSEK6, derived from swine embryo kidney proved to be a suitable host for the propagation of a hemagglutinating encephalomyelitis virus, strain 67N. Infected cells showed clear cytopathic effect as early as 24 hours incubation at 37 degrees C. Plaques easily visible to the naked eye were also produced under agar overlay medium. The infective titer of 3rd passage level in the cells was in the order of 10(8) PFU per ml. Detecting antibodies against this virus strain in swine sera was considered to be more accurate by neutralization test than by hemagglutination inhibition. PMID- 7861993 TI - Bacterial protein toxins acting on the cell cytoskeleton. AB - A number of bacterial protein toxins are known to exert their cytotoxic activity via a modification of cytoskeletal components. Some toxins induce the ADP ribosylation of actin whereas others interact with the cytoskeleton by an unknown mechanism. Understanding the mode of action of such toxins at cellular level could provide useful information on their role in vivo as virulence factors. PMID- 7861994 TI - Admissions procedures to medical schools. PMID- 7861995 TI - Selection of medical students: the Beer-Sheva perspective. AB - In many Western medical schools with a low attrition rate the selection of medical students represents the key hurdle for admission to the practice of medicine. The process therefore deserves careful attention. Described herein are impressions and conclusions from almost two decades' experience in selecting medical students at the Ben-Gurion University in Beer-Sheva, Israel. Emphasis is placed on personal qualities as determined by an interview process of those students who pass a relatively lenient academic threshold. Interviewing is carried out by teams of two, one of whom is a doctor, and each candidate who is accepted is interviewed by four members of the admission committee. Emphasis is placed on clear goals for the interview process, carefully selected and trained interviewers and continual review of the process. In spite of the inherent limitations of a subjective interview process we feel that it offers considerable advantage over other approaches in student selection. PMID- 7861996 TI - Statement on medical education in neurology. Working Group for Neurology and the World Federation for Medical Education. PMID- 7861997 TI - Tutoring in problem-based learning: a teacher development process. AB - Undergraduate medical curricula have become increasingly innovative in order to better prepare their graduates to enter practice, with the most notable innovation being the introduction of problem-based learning (PBL). This paper describes Dalhousie University's transition to PBL, from a teacher development perspective. The paper reinforces the need for a well-designed teacher development process that is carefully implemented and evaluated in order to ensure a successful curriculum change. A seven-stage process for teacher development of tutors at Dalhousie is described, and programme evaluation data are reported from both students' and teachers' points of view. The results from the evaluation are very positive and suggest ways of improving the teacher development process. These improvements are described, as well as future plans in this area. PMID- 7861998 TI - Peer tutoring and student outcomes in a problem-based course. AB - Does peer-tutoring affect students' educational outcomes in problem-based learning? Students' characteristics and outcomes were compared along 14 successive classes of a problem-based learning course in the University of Brasilia medical programme. In the first stage of this time series, 26 teacher tutored groups were formed; in the second stage, 50 groups had both teacher- and peer-tutoring. Both groups had equivalent characteristics in stages one and two as regards membership size and composition (students' learning style, self confidence and motivation to learn). Results showed that scores for problem solving tests and self-evaluation of skills were not significantly different between first and second stage groups. However, scores of meaningfulness of course experience and group work usefulness were significantly higher in the peer tutoring stage. Significant positive correlations were found between scores of meaningfulness of course experience and both self-evaluation and group work usefulness but not between the first measure and group size or motivation to learn. The findings suggest that peer-tutoring can facilitate group work without sustained loss of cognitive achievement in long range conditions of problem-based learning experience. PMID- 7861999 TI - Effects of cadaver dissection on the attitudes of medical students. AB - A study was conducted to determine whether the attitudes of medical students to death and caring changed during the 3 months following exposure to cadaver dissection. All first-year students were invited to complete a questionnaire immediately before their initial cadaver dissection experience, after 6 weeks, and after a further 3 months. The questionnaire reflected attitudes to death, violent death, death of someone known to the respondent and caring when someone known to the respondent is seriously injured. Ethnicity and previous exposure to dying has no effect on responses, but overall men students' reactions were significantly less than for women (P < 0.001). The responses given on the final part of the questionnaire after 3 months were significantly lower than those to most questions in the first part of the questionnaire. The exceptions were those questions where the subject in the given scenario was known to the respondent, where reactions were rated significantly greater (P < 0.001) in the follow-up questionnaire and can be explained on the basis that they were a personal referent. Students rapidly develop a coping mechanism which enables them to view cadaver dissection as an occupation quite divorced from living human beings. During these early months of training solicitude decreases for those who die who are unknown to them, but concern for personal referents increases. Educators should be aware of the dramatic change of attitudes among students and the process of professionalization which might influence their caring of future patients. PMID- 7862000 TI - Professional behaviour of medical school graduates: an analysis. AB - Recent graduates (1989-1990) of a traditional school of Chinese medicine were assessed by observers using a 10-item scale for professional behaviour in the non cognitive realm. Overall, 10.7% of the graduates had low ratings on this scale. Of those who scored in the top two quartiles on this scale, 71.4% reported that 'Professional ethics' was the key determinant of their professional behaviour, whereas legal concerns were the prime motivator for only 3.6% of the top scorers. It was also found that students' scores in the medical ethics course correlated with their professional behaviour score to a statistically significant degree. PMID- 7862001 TI - Dermatology examination performance: wide variation between different teaching centres. AB - Three hundred and one clinical medical students in four universities took the same 50 question MCQ dermatology examination after their dermatology teaching. In one centre, half the students had had additional teaching; these students performed better (mean score 47.5%, n = 29) than those who had no extra teaching (mean score 40.9%, n = 29). In another centre, the students' mean score improved from 24.1 (SD = 6.7) before to 41.6 (SD = 7) (n = 46, P < 0.001) after their dermatology teaching. The different subject areas covered by the examination were analysed separately. In the lowest scoring centre (mean score 34.0, SD = 9.4) the students scored lowest in 9 of the 14 subject areas. In the highest scoring centre (mean score 47.5, SD = 9.9) students scored highest in 7 of these 14 subject areas. This study enabled questions of high discriminatory value to be identified for future use. The use of the same examination in different centres provides feedback for the centres concerning strengths and weaknesses of their teaching. PMID- 7862002 TI - Do the clinical years change medical students' attitudes to old people? AB - Students at the Christchurch School of Medicine have previously been shown to demonstrate a significant improvement in attitudes and knowledge about old people after a 5-week attachment in their first clinical year (fourth year of their medical course). The original cohort were retested between 1 and 3 years after graduation. A modified version of the Rosencranz-McNevin Semantic Differential Scale was used to measure general attitudes to old age and a Likert scale to measure attitudes to medical care and knowledge. Attitudes measured by the Rosencranz-McNevin Scale showed no change between the completion of the fourth year attachment and graduation. The Likert scale showed no change in knowledge but the attitude score showed a worsening (P < 0.001). Knowledge and attitudes of graduates who had completed a house office attachment in health care of the elderly were better than those who had not (knowledge P < 0.01, attitude P < 0.06). PMID- 7862003 TI - A survey of medical undergraduate community-based teaching: taking undergraduate teaching into the community. AB - This article summarizes the findings of a survey investigating the extent to which medical schools in the United Kingdom have developed community-based undergraduate teaching: the types of courses being run and their content; whether they are being evaluated; and how the students are assessed. Courses have been categorized under four main headings: (1) based in general practice, for teaching about general practice as a clinical specialty or using practice patients for teaching general medicine and basic clinical skills; (2) community-oriented, led by GP or community tutors; (3) specialist teaching led by hospital consultants; and (4) agency-based teaching. Twenty-eight schools responded to a written request for information and details of 83 courses were received. PMID- 7862004 TI - Uncertainties and ambiguities: measuring how medical students cope. AB - To develop psychometric measures specific to the ambiguities encountered in medicine and determine their value in predicting medical students' attitudes towards patients and their choice of residency, we administered to senior and first-year medical students a 25-item Likert-type questionnaire to assess their intolerance of ambiguity (ITA). Factor analysis yielded two dimensions that were converted to scales: 'Aversion to uncertainties in clinical medicine' (ITA1) and 'Preference for highly structured training environs' (ITA2). First-year students scored higher on ITA1 and lower on ITA2 than seniors. An excessive reliance on high-technology medicine, a negative orientation toward psychological problems, and Machiavellianism predicted ITA1. ITA1 was the best predictor of senior medical students' negative attributional style toward hypochondriac, geriatric and chronic pain patients. The following rank order of seniors' career choice was predicted by ITA1 scores: internal medicine, psychiatry and family medicine (lowest); radiology, surgery and anaesthesiology (highest). And by ITA2 scores: surgery, obstetrics and gynaecology, and surgical subspecialties (lowest); radiology, psychiatry and anaesthesiology (highest). We concluded that personality traits and role characteristics which predict 'Aversion to uncertainties in clinical medicine' are maladaptive to managing many primary care patients, and this mismatch is reflected in seniors' residency choice. PMID- 7862005 TI - The need for teaching in medical audit: a survey in one medical school. AB - A questionnaire survey was carried out among senior clinical teachers at Newcastle upon Tyne Medical School, UK about their current practice and attitudes toward the teaching of medical audit in the undergraduate curriculum. A response rate of 88% was achieved. Less than a fifth of respondents provided such teaching, but the majority were in favour of seeing the topic introduced. A variety of teaching methods were used, and feedback from students was generally favourable. A number of concerns were expressed, including the problem of curriculum overload, the timing of the teaching, and the need to ensure that the learning was experiential with a minimum of theoretical teaching. Those who were in favour of introducing such teaching, or who were unsure, were also concerned about pressures on curricular time, but some felt in addition that the topic was more appropriately a postgraduate one. A short attitude scale demonstrated a skew towards favourable attitudes among the whole group. The implications of the survey for teaching about audit and quality are discussed. PMID- 7862006 TI - The art of medicine revisited. PMID- 7862007 TI - Training of overseas-qualified doctors. PMID- 7862008 TI - Health promotion and disease prevention: integration into a medical school curriculum. AB - Many authorities have identified deficiencies in the education of medical students in health promotion and disease prevention. This report describes an attempt to address this problem through the longitudinal integration of health promotion and disease prevention into several major courses in the student curriculum at Harvard Medical School. We used adult learning theory to develop the curricular approach, and designed educational experiences to match the professional development of the student at different phases of medical education. Primary, secondary, and tertiary prevention were particularly germane for students in the first, second, and third years, respectively. During clerkships in the third and fourth years, especially those with a focus on ambulatory patients, students built upon earlier experiences to integrate health promotion and disease prevention into clinical practice. By unifying the teaching of disease prevention with several major required courses, we aimed to create an environment in which students could experience their learning about disease prevention in the same manner that we aspired to have them practise it: integrated throughout clinical medicine. PMID- 7862009 TI - Implications of HIV infection and AIDS for medical education. AB - What implications on medical schools have HIV infection and AIDS, as the schools reshape their curricula to meet the General Medical Council's new requirements? (General Medical Council 1993). A recent Institute of Medical Ethics' (IME) enquiry suggests: (1) that each medical school should have a specific policy to coordinate teaching on HIV infection and AIDS, and to maximize students' clinical contact with patients who have the virus; and (2) that medical students should be encouraged to develop self-awareness and skills in communication and ethics. PMID- 7862010 TI - Educational intervention in pharmacy students' attitudes to HIV/AIDS and drug misuse. AB - By providing injecting equipment to drug misusers, community pharmacists in the UK may become involved in preventing the spread of HIV via the intravenous route. Over 60% of pharmacy graduates from the School of Pharmacy enter community pharmacy and, as part of their undergraduate course, attend a series of lectures and seminars on HIV/AIDS and drug misuse. The aim of this research was to: (1) investigate students' attitudes to these subjects; (2) assess the students' knowledge of HIV/AIDS; (3) evaluate any change in level of knowledge or of attitude after attending the course; and (4) investigate students' attitudes towards the teaching of these subjects. A questionnaire was administered to students before and after their undergraduate course. The level of knowledge increased significantly after attending the course. Students were asked their opinion on the teaching of HIV/AIDS and drug misuse at the School of Pharmacy. After the course, significantly more responded 'good' or 'very good' with regard to teaching on social issues in drug misuse, rehabilitation and treatment of drug misusers, and health education on HIV/AIDS. There was no significant change in attitude, after the course. Attitude to HIV/AIDS and drug misuse was found to be unassociated with previous experience of working in pharmacies supplying injecting equipment and prescribed methadone. Both attitude and pre-course assessed knowledge were significantly associated with race and religion. These results indicate that attending the course had the effect of increasing knowledge of HIV/AIDS and increasing confidence in counselling clients. The perception of the teaching was also seen to be more positive. PMID- 7862011 TI - Computer education: attitudes and opinions of first-year medical students. AB - Students' attitudes toward medical informatics were evaluated with self administered questionnaires, answered by 140 (77%) first-year medical and dental students. Fourteen per cent classified their computer literacy as negligible and 49% as deficient. Ninety-six per cent had used a computer before and 59% used one regularly. Nineteen per cent had computer education in secondary school and a further 16% attended courses given by a computer company. Only 16% read regularly about informatics. These results are similar to those observed in more industrialized countries, except that high-school education is more deficient. To 93% of these students, computer literacy is important for doctors, and to 85% computers may be very useful in many areas of health care. In the opinion of 66% of students, the computer-based patient record will be available within the next 3 to 10 years. Women showed lesser computer literacy (77% computer illiteracy to 39% in men), but there were no relevant differences in attitudes, behaviour and beliefs towards medical informatics between gender, for the same level of computer literacy. Computer education in the undergraduate curriculum was demanded by 92%, and 75% of these preferred an elective course. Weekly hours suggested for lectures should be 1 (54%) or 2 (42%), and for hands-on practice 2 (54%) or 4 (31%) hours. The curriculum should include medical applications (83% of students), information science theory and technology (44%), micro-informatics (44%), bibliographic database search (27%), programming languages (23%) and statistical packages (23%). Gender, computer literacy or course did not correlate significantly with students' opinions about the contents of undergraduate education. PMID- 7862012 TI - Internet tools in the medical classroom. AB - The Internet contains a vast amount of medically relevant information. In order to access this information, however, many networks require one to master applications written in UNIX, an operating system considered by many not to be user friendly. Although these tools may be available on campus, it is difficult to teach their use unless there is some immediate benefit to the already busy user. From that standpoint, it is important for instructors to realize that common UNIX applications can be utilized as classroom tools to significantly enhance the learning experience by facilitating teacher/student communication. Also, whilst the student enjoys greater communication with the instructor (and with other students) he/she is also becoming adept at using information management tools. PMID- 7862013 TI - Unrealistic optimism: a behavioural sciences classroom demonstration project. AB - Unrealistic optimism may contribute to risky health practices and to a delay in seeking treatment for medical conditions, as most individuals perceive themselves to be at little risk for various disorders. It is thus an important concept to present to medical students as part of their behavioural sciences training. Social psychological concepts such as unrealistic optimism may appear, on initial presentation to students, to be a misjudgement based on faulty understanding of risk estimates by the general population. This project aimed to teach the principle of unrealistic optimism by having students document their own beliefs about health risks. Students rated their own risk, relative to other classmates, of experiencing a range of 17 health problems. Questionnaires were completed by two classes of medical students (n = 257). Class results showed varying levels of unrealistic optimism for all 17 conditions. Males and females differed significantly on three of the 17 conditions. Student data were obtained rapidly in a large didactic setting and served to illustrate the concept of unrealistic optimism which was subsequently taught in class. Such exercises may be a useful teaching aid to students providing them with feedback on their own cognitive processes and illustrating that they display cognitive distortions similar to those of patients. PMID- 7862014 TI - Ethics and animal issues in US medical education. AB - Increasing public and regulatory agency concern about a variety of animal protection issues that affect the field of medicine have made these issues increasingly relevant to medical school curricula. The purpose of this study was to assess the availability and forms of medical school training relating to ethical, conceptual, and societal concerns in the use of animals within the field of medicine and the perceived need for such training. Questionnaire surveys were mailed to the Deans of the 125 accredited US medical schools, and completed by Deans or their designees within the same medical institution. Questionnaire recipients were informed that results would be compiled in a fashion that did not identify specific individuals or institutions. Survey responses were obtained from 84 medical institutions (67% response). Sixty respondents (71%) indicated that their medical school offered or sponsored some type of activity related to ethical and conceptual concerns in the use of animals in medical research and training. Most schools (43) offered informal discussions/seminars relating to these issues, but nine schools offered full formal courses with up to 15 lectures on these topics. Programme content and perceived need for additional instruction varied greatly amongst respondents. The results suggest a wide diversity amongst US medical schools in the availability and perceived importance of medical school training relating to ethical and conceptual concerns in the uses of animals in medicine. It is proposed that instruction in these areas be pursued with more concerted efforts to address the growing body of knowledge about non-human beings and the ethical implications of such knowledge. PMID- 7862015 TI - Does learning emergency medicine equip medical students for ward emergencies? AB - The aim of this study was to assess the competence of senior medical students in recognizing and managing life-threatening ward emergencies and to compare the competence of a group that had received emergency medicine teaching with one that had not. This was achieved by asking 60 final year medical students to complete a structured written clinical examination designed to test these skills. Comparisons were made between the group that had received emergency medicine teaching (the 'taught' group) and that which had not (the 'untaught' group) with respect to numerical scores on the examination and the number of fatal management errors committed. The 'taught' group had an average total score of 285/400 compared with an average score of 223/400 for the 'untaught' group (P < 0.001). The 'untaught' group committed 0.25 fatal errors per student per case compared with the 'taught' group that committed 0.06 fatal errors per student per case (P < 0.001). There is considerable scope to improve the competence of senior medical students for dealing with life-threatening ward emergencies. Students who had received emergency medicine teaching scored significantly better than those who had not suggesting that emergency medicine teaching is a suitable tool to help equip medical students to deal with life threatening ward emergencies. PMID- 7862016 TI - Stress management for clinical medical students. AB - This study evaluates a new stress management course for medical students offered through the Occupational Health Unit, Royal Free Hospital, London. It was offered to students in their first clinical year, which has been shown to be a highly stressful time. The course took place over 3 weeks, with one 2-hour session each week. Students completed questionnaires about mood, attitudes and causes of stress at the beginning of the year, and again one year later. The uptake of this optional course was 17%. Attendees, compared with non-attendees, were more anxious, less satisfied with themselves and their life, and perceived both work and outside functioning to be poorer. Over this first clinical year, non attendees became significantly more dissatisfied at work and increasingly perceived their functioning at work and outside to be poorer whilst attendees showed no such deterioration over the year. Attendees completed the questionnaires before and after the course, and at two time points prior to starting the course when on the waiting list. Improvements in reported work functioning were found after the course, and this change was significant compared with the waiting list controls. These results are consistent with the attendees' own reports that they found the course helpful. These results show that stress management provides long-term protective effects as well as short-term benefits. PMID- 7862017 TI - Comparison of two types of paediatric curricula. AB - Paediatrics is taught in the fourth year at two different hospitals in Leeds with a common examination at the end of the courses. Apparent discrepancies in the results obtained between students attached to the hospitals prompted a comparison of the results over a 2-year period. The paediatric curriculum in hospital A is taught in an integrated design with obstetrics/gynaecology whereas hospital B follows a more conventional discipline-based module. Significant differences were found with consistently lower results achieved from the integrated course. Further analysis of the students' abilities by assessment of two examinations in pathology where all students are taught in the same course revealed that students subsequently assigned to hospital A were significantly less able. This study highlighted the importance of further evaluation before assuming that the curriculum design is solely to blame for differences in final assessments. However, continued dissatisfaction with the integrated course design by both students and teachers still necessitates review of the curriculum design. PMID- 7862018 TI - House officers in general medicine: their perception of educational value of rotation components. AB - As curriculum planners in general medicine residency training programmes we were concerned about house officers' anecdotal reports that hospital work requirements often overshadow individual learning goals. After each of five rotations, we asked residents to identify the educational 'usefulness' of certain rotation components which can be included in three categories; team members, work-related activities and educational events. Of 165 surveys distributed, 127 (77%) were returned. Data were analysed by residency year and by all years combined. The mean overall perception of learning was 3.9 out of a possible 5 points suggesting that residents do find some learning value. Results suggest that different residency years vary as to the significance of specific educational components. The importance of faculty/resident relationships to residents' perceptions of learning value was highlighted in particular. PMID- 7862019 TI - The personal tutor system: an evaluation. AB - The stressful nature of medical student training is being increasingly recognized. This study describes a questionnaire survey of the long running personal tutor system (intended to help with social as well as educational needs of clinical students), at a London medical school. Just over one half of students and one third of tutors were highly satisfied with the system. Satisfaction in students was linked with regularity, but not frequency, of meetings, being 'chased' by tutors, and engaging in social as well as educational activities. A small but worrying percentage of students reported that they would not be able to share personal or academic difficulties with tutors, highlighting the need for other avenues of support/counselling to be made available to students. PMID- 7862020 TI - A rating scale for tutor evaluation in a problem-based curriculum: validity and reliability. AB - An instrument has been developed to assess tutor performance in problem-based tutorial groups. This tutor evaluation questionnaire consists of 13 statements reflecting the tutor's behaviour. The statements are based on a description of the tasks set for the tutor. This study reports results on the validity and reliability of the instrument. Confirmatory factor analysis showed that a three factor model fitted the data reasonably well. The three factors are: (1) guiding students through the learning process, (2) content knowledge input, and (3) commitment to the group's learning. Generalizability studies indicated that the rating scales provide reliable information with student responses of existing tutorial group sizes. It is concluded that the tutor evaluation questionnaire is a fairly valid and reliable instrument that can be used in staff development programmes. PMID- 7862021 TI - Young hospital doctors after night duty: their task-specific cognitive status and emotional condition. AB - Sleep deprivation is an unpleasant burden of young hospital doctors during their medical training. It may disrupt the balance between coping strategies available to them and the professional demands encountered. Impaired medical care offered by sleep-deprived juniors may be a consequence. Valid research work on this subject is rare and surprisingly contradictory. Therefore, we evaluated the task specific cognitive status and emotional condition of 40 young hospital doctors (27 men and 13 women, 29.9 +/- 2.9 years of age) at the University of Tuebingen, all of whom were in the beginning of their academic career. Subjects were tested twice acting as their own control, once at 8.00 am after a night off duty (OD) (at least 6 hours of uninterrupted sleep), and once at a similar time after a night on call (OC) being in the hospital for 24 hours. Standardized and reliable psychometric tests thought to represent daily routine medical function were performed. On-call activities were recorded by means of a sleep diary, whereas a questionnaire interrogated aspects of private and professional life. Neuropsychological function deteriorated significantly: number connection test (per cent of norms +/- SD, 103.2 +/- 9.8 OC vs 107.8 +/- 10.5 OD, F = 27.7, P < 0.001), things-to-do list (correct items +/- SD, 6.7 +/- 1.2 OC vs 7.4 +/- 1.5 OD, F = 12.7, P < 0.01), Vienna reaction timer (per cent of norms +/- SD, 95.6 +/ 9.0 OC vs 97.7 +/- 10.4 OD, F = 4.8, P < 0.05), Stroop test (T-values +/- SD, 59.7 +/- 6.3 OC vs 64.6 +/- 7.1 OD, F = 37.1, P < 0.001), ECG test (correct responses +/- SD, 38.3 +/- 7.3 OC vs 43.4 +/- 6.5 OD, F = 45.2, P < 0.001) and status of mood (T-value +/- SD, 60.3 +/- 9.0 OC vs 54.0 +/- 6.6 OD, F = 19.6, P < 0.001). Cognitive function and mood status of young hospital doctors after a night on call decrease considerably. In view of the special vulnerability of medical trainees to occupational stress all efforts are warranted to reduce sleep deprivation in the medical profession. PMID- 7862022 TI - Training for medical teachers: a UK survey 1993 (Biggs et al.) PMID- 7862023 TI - Drugs for migraine. PMID- 7862024 TI - [Hyperinsulinemia in women with hyperandrogenemia]. AB - In the peripheral blood serum from 24 females with hyperandrogenemia and 12 controls we determined concentrations of total testosterone (T), dehydroepiandrosterone-sulfate (DHEA-S), sex hormone binding globulin (SHBG) and insulin, and calculated Free Androgen Index. In hyperandrogenemic patients we found significantly higher mean concentrations of total testosterone when compared to the controls (n = 192; 3.5 + 1.9 vs n = 76; 1.9 = 0.9; P < 0.001), insulin (n = 95; 23.2 = 15.1; vs n = 33; 9.9 = 4.8; p < 0.001) DHEA-S (n = 70; 6.2 = 1.6 vs n = 27; 3.6 = 1.9; p < 0.001), FAI (n = 65; 27 = 32.9 vs n = 33; 3.9 = 2.1; p < 0.001) while the levels of SHBG in hyperandrogenemics were significantly lower than in the controls (n = 67; 24.6 = 15.9 vs n = 33; 52.8 = 19.3; p < 0.001). We found a positive correlation between the relative body mass and insulin concentrations (r = 0.67) in the form of the repeated sampling mean values; between the relative body mass and the mean values of the total testosterone concentrations (r = 0.42) and between the total testosterone concentrations and insulin (r = 0.32). PMID- 7862025 TI - [Informative morphogenetic variants--guidelines for the diagnosis of major malformations]. AB - Informative morphogenetic variants are present both in healthy population and in certain diseases and genetic syndromes. They are defined as "structural anomalies with no medical or aesthetic consequences" (1) or "unusual morphologic features with no relevant medical or cosmetic consequences on the carrier" (2). The investigation was initiated when evidences from the foreign literature were found suggesting that children with polythelia more frequently show hereditary and acquired urinary tract malformations than in general population, that is, in children with no IMV. OBJECTIVE: to determine the correlation between the onset of polythelia and hereditary and acquired urinary tract major malformations. On the basis of the results and the discussion we might conclude the following: among the children with polythelia a statistically significant majority has hereditary and acquierd urinary tract major malformations when compared to those with no IMV. PMID- 7862026 TI - [From tics to the Gilles de la Tourette syndrome]. AB - We report a case whose progressive course and forms of manifestation of generalized tic movements indicate relatively rare Gilles de la Tourette disease. It is characterized by the triad--non-coordinated mobility-dyskinesia, echolalia corporalia, epilepsy and according to the current data from the literature, compulsive behavior, phobias and sometimes episodes of insanity in the advanced stage. The clinical case we report as well as cases from the world literature is rather dubious, asks for prolonged follow-up and has polymorphic symptomatology and necessitates a multidisciplinary therapeutic approach. Beside the clinical features, laboratory findings has also been discussed. PMID- 7862027 TI - [Clinical and epidemiologic characteristics of ischemic heart disease in a group of physically handicapped individuals (blind and mute)]. AB - Our long clinical experience, with observations of some authors as well, indicate that the epidemic data of the prevalence of ischaemic heart disease (I.H.D.) is significantly reduced in some physically handicapped people (the blind and the deaf-mute) if we compare them with the similar ones who have not such anomalies. With no regard to patho-physiologic mechanism of such condition, 233 examinees of both sex, chosen by the method of accidental choice, were examined by clinical, ECG, and laboratory (non- invasive) methods and divided into three groups: the blind 81 (34.76%), the deaf-mute 76 (32.61%), and industrial workers 76 (32.61%) who were taken a as control group. The obtained results show that the incidence of I.H.D. (4,56%), and the control group 11 (8,36%), which, from the point of statistics, offer a significant piece of information. PMID- 7862028 TI - [Microalbuminuria in diabetics treated with insulin for more than 30 years]. AB - Microalbuminuria was determined in the urine of 6 diabetics who had been treated with Insulin for over 30 years an had a normal kidney function. The values gained by the radial immunodiffusion method (VLC--Partigen Albumin) range from 0.001 gr/l to 0.008 gr/l of albumins in the urine. These values are much below the risky ones (over 0.020 gr/l), which signalize the evolution to the macroproteinuria and the development of the diabetic nephropathy. Over 30 years duration of the insulin-dependent diabetes, with no macroproteinuria pretors on the expression of diabetic nephropathy. 5 locus which is known to have the influence on the intensity of the immunological response. PMID- 7862029 TI - [Relation between the histological picture, tumor location, sex and age of patients with skin carcinoma]. AB - The data from 1020 patients (517 males and 503 females) with histologically proved skin carcinoma, with regard to the type of the tumor, localization of changes, sex and age were taken from hospital registries. Statistical methods showed that planocellular and basocellular neoplasms were found in 98.53% of the cases. In 94.41% they were localized on the head. Basocellular type was more frequently found than planocellular both among the males and females. The males with planocellular neoplasms were significantly younger than the females because of the higher incidence of this type on the lower lip, which develops earlier in life. Significantly more frequent localization in females is on the nose. Our results are in harmony with the findings of other authors. PMID- 7862030 TI - [Arterial hypertension as a risk factor in ischemic heart disease]. AB - Three groups, with one hundred subjects in each, were formed randomly. The first group consisted of members from urban area, second of country population, both having arterial hypertension, while in the third group were subjects without arterial hypertension. Analysis was made in order to find the relation between diastolic component of blood pressure, the level of hypertension and the period of its duration as well as the difference of these parametres between the urban and country population. The incidence of the ischaemic heart disease was considered in all three tested groups. The investigation showed the absence of considerable statistical difference in the level of hypertension and the period of its duration between the urban and country population. Ischaemic heart disease is equally presented in all three groups. It appears more frequently in men than in women, but the difference is not statistically important. Analysing the relation between frequency of appearance of the ischaemic heart disease and the level of hypertension it was found that it appears more frequently in subjects with slight arterial hypertension, with a high level of correlation. PMID- 7862031 TI - [Calcium antagonists as the initial monotherapy in arterial hypertension]. AB - The most modern trends in the artery hypertension treatment recommend using the individual remedy. The modern approach to the therapy of this disease points more and more to the use of the calcium antagonists but in the scope of monotherapy. In the total mass of the cured (200), in the treated group are used Nifedplan and Verapamil, while the tested patients of the control group were treated by metilodop and hyginic--dietetics treatment. With regard to the medication the patients matched in number. The use and the impact of Nifedipine and Verapamil onto the systolic and diastolic components of blood pressure point to the statistically significant antihypertensic efficiency of both preparations. The unwanted effects are practically irrelevant which gives to the calcium antagonists priority at choice. Introducing the calcium antagonists into clinical practice is a great progress in the pharmacotherapy of many cardiovascular illnesses. They are nowadays irreplaceable at discussing the effective treatment of artery hypertension, heart ishemical illnesses, heart arrhythmias and hypertrophic obstructive myocardiopathy. PMID- 7862032 TI - [The role and importance of intraoperative cholangiography in modern biliary surgery]. AB - The aim of the study is to show that routine use of intraoperative cholangiography may significantly reduce postoperative complications after cholecystectomy. We made a prospective study on 200 cholecystectomized patients in the period IX 1988-III 1989. Patients are divided in two groups: A--control group consisting of 100 cholecystectomized patients without intraoperative cholangiography and B--also consisting of 100 patients with routinely used intraoperative cholangiography. Results are given in the following table where the complications are separated by the time of appearance, specific signs and symptoms. CONCLUSION: Routine use of intraoperative cholangiography significantly reduces the number of complications (A:B = 19:9) which is statistically significant (chi-square test. p < 0.05). PMID- 7862033 TI - [Personality characteristics of alcoholic patients and its effect on the therapeutic process]. AB - By use of the PIE (Emotions Profile Index, R. Plutshik-H. Kellerman) 83 male alcoholics have been examined in the course of the group therapy Values higher that the average were recorded in the following categories: Deprivation, Destructivity and (partially) Protection. Values below the average were found in relation to: Research, Orientation and (partially) Rejection. Between the Destructivity and Protection a conflict was found. The obtained findings mostly interferred with the therapy. PMID- 7862034 TI - [Specific therapeutic treatment of alcoholic single persons in clinical practice]. AB - We analyzed the experience of authors treating alcoholics-singles and concluded that the observed group is homogenous only with regard to the fact that the subjects have not been married but rather heterogenous with regard to the sex, age, education, previous marital experience and attitudes toward the family. Discussed are problems of the assistants in the treatment, acceptance of the therapy group and the defeat of the heterogenousness. PMID- 7862035 TI - [Differential diagnosis and therapeutic problems in tics and obsessive-compulsive disorders during the developmental age]. AB - In order to point to the differential-diagnostic issue of tics and obsessive compulsive disorders because of similar clinical manifestations of some forms of tics with compulsive behavior, and ebcause of frequent obsessive features found in children with tics, we have examined 121 patients with tic and 9 patients with obsessive-compulsive disorder. In the tic group we found a significant occurrence of differently manifested obsessive line, while in the compulsive disorders group we found a great percentage of tics. Attempts made in order to differentiate these two clinical pictures in practice were based on the recognition that in both cases we deal with a unique etiopathogenetic factor in the form of frustration which in some children cause a feeling of tension which in some cases further manifests itself in the deterioration of voluntary movements initiating tics, sometimes provoke defensive mechanisms leading to the obsessive-compulsive syndrome and sometimes both issues are present. Such recognition implicates a more complex approach to the child's personality by neglecting the differences between the two disorders and includes a therapeutic program consisting of psychomotor reduction and relaxation, medication, parent assistance and school cooperation. PMID- 7862036 TI - [Organization and professional activities at the Zrenjanin Health Center]. PMID- 7862038 TI - [Lung hyperinflation and verification of its functional parameters]. AB - A functional testing of lung hyperinflation parameters have been performed by two methods: body-plethysmography and helium single-breath method. The results obtained have been thereafter compared. In a group of 15 healthy patients no significant differences have been established except for the residual volume (RV). However, in a group of patients with C.O.P.D. significant differences among parameters have been established most of them for RV. The body-plethysmography method has no equal, however with the help of helium method it is also possible to measure out the closed noncommunicative airspaces in the lungs. PMID- 7862037 TI - [Occurrence of tics, enuresis and hyperkinetic behavior in children with speech disorders]. AB - The aim of the study was to assess the share of positive correlation between speech disorders and tics, urination disorders and hyperkinetic behavior. The subjects were: E--experimental group with 700 children (459 boys and 241 girls) 6 14 years old, with speech pathology, C--a group of 510 (271 boys and 239 girls) healthy children from kindergartens and schools, aged 6-10. The transversal method along with clinical and statistical methods were used. RESULTS: correlation between speech discorders and ticks--this phenomenon was regarded as an infrequent event and checked by the Poisson Distribution A and B and the Chi square test. The obtained results: X2 = 26. 83 P--0 showing that the difference is significant and that tics are more often found in the E than in the C group. Correlation between speech disorders and enuresis--it is necessary to determine features of the incidence of the phenomenon which also rarely occurs. These data were also checked by the Poisson distribution A and B, and Chi-square test. The obtained results: X2 = 59.91 P --> O indicating that in the E group the occurrence of enuresis was significantly higher than in the K group. The correlation between the speech function and hyperkinesis was checked by Chi square test. Since X2 = 2.31 the difference was not statistically significant. PMID- 7862039 TI - [Actinomycosis of the minor pelvis associated with prolonged use of intrauterine contraceptive devices (IUD)]. AB - Pelvic actinomycosis is a rare disorder caused by Gram-positive anaerobic bacteria Actinomyces Israeli, and it is commonly associated with the prolonged use of IUD. The authors present two cases of pelvic actinomycosis in patients who used IUD for prolonged periods of time (eight and fourteen years). The diagnostic procedure in both cases lasted long and the definite diagnosis was made only after the pathohistological examination of the material taken during the surgical treatment. Actinomyces Israeli should be considered as one of the causes of the diagnosed pelvic inflammation especially when it is associated with the prolonged use of IUD. PMID- 7862040 TI - [A compound odontoma]. AB - Compound odontoma is a malformation manifested as a localized lesion before a non erupted or displaced tooth consisting of numerous small tooth-like components. The lesion develops asymptomatically. The recognition of its clinical features helps the prevention of deformities and caries in the adjacent teeth by an on time and adequate surgical treatment. PMID- 7862041 TI - [The role of Epstein-Barr virus in patients with mononucleosis syndrome and lymphadenopathy]. AB - In a two-year period 117 patients with diagnosed mononucleosis sundrome and 207 patients with diagnosed lymphadenopathy were serologically examined. Of these 57 patients were immunodeficient and 267 immunocompetent. Acute infection with Epstein-Barr virus was proved in 17.09% of the cases with mononucleosis syndrome, 13.04% with lymphadenopathy i.e. 8.77% of the immunodeficient and 15.73% of the immunocompetent patients. The significantly highest rate was recorded among schoolchildren and adolescents (from 7 to 27 years of age). The occurrence of other viral (adeno-and cytomegalo-) and non-viral infections (toxoplasma gondii, chlamydia) in these patients has also been analyzed. PMID- 7862042 TI - [Scintigraphy of the vascular supply of the liver in the differential diagnosis of hemangioma, in malignant processes and cystic formations in the liver]. AB - The aim of the research is to establish and confirm the diagnoses of patients with suspected haemangioma of the liver with completed ultrasonography. A group of 92 patients were checked by scintigraphy after the equilibration of marked eritrocytes in the circulation. After the marking dose of 99mTc-Sn-PYP in a dose of 555 MBq scintigraphy and static scintigram of the liver (early and late, after 3 hours) were done. During the clinical studies the classic scintigraphy of the liver by 99mTc-S-coloid was done in all the patients. After the study it was concluded that there was a partial gathering of the radioisotopes in early scintigrams which was more evident in the late ones especially in the areas which represented focal-cold zones in the classic scintigrams. PMID- 7862043 TI - [The importance of monitoring and correcting the hydromineral status in general anesthesia in children]. AB - Specific physiological features of the child's organism necessitate a preoperative assessment of hydromineral and acidobasic status and its correction in order to reduce intraoperative complications and accelerate postoperative recovery. The analysis was carried out in children who were operated on in general anesthesia in the period of one year. Their hydromineral and acidobasic status was assessed. On the basis of the clinical picture and laboratory analyses we assessed the dehydration and metabolical changes and made the corrections preoperatively. Given are tables for the compensation of basic physiological liquid and electrolyte quantities, a guide for the assessment and the correction of the dehydration levels and the correction of metabolical changes. We also gave tables for the compensation of liquid during the operation in general anesthesia. In the conclusion we review basic principles in the preparation for an urgent operation in general anesthesia in relation to hydromineral and acidobasic status as well as the administration of liquid during the operation. PMID- 7862044 TI - [Helicobacter pylori in patients with diseases of the upper part of the gastrointestinal tract]. AB - Among the patients subjected to esophoagogastroduodenoscopy because of different clinical indications, 108 were examined for the presence of Helicobacter pylori in the antral gastric mucosa. Microbiological analysis of the antral gastric mucosa biopsies were conducted by direct microscopy, the urease test and by growing in nutritious media. Positive findings were recorded in 38 (86.36%) patients with endoscopically diagnosed chronic gastritis, 29 (80.56%) patients with duodenal ulcer and 19 (67.86%) patients with ventricular ulcer. The majority of the positive findings were recorded by direct microscopy--86 (79.63%) while the bacterial culture was positive in 66 (61.11%) cases. PMID- 7862045 TI - [The effect of stress and personality structure on the onset and severity of the clinical picture of psoriasis]. AB - On a sample of 38 psoriatic patients we tried to determine the relationship between neurotic disorders (operationalized MMPI) and the number and hazardous effects of stressful events on the one hand and the severity of the clinical picture and the time of the onset of psoriasis on the other. In our sample neurotic disorders are much commoner than in the general population indicating that they might represent one of the most significant factor of etiology, complications and prevention. The last hypothesis is based on the results showing that neurotic psoriatics develop psoriasis significantly later than non neurotics. We haven't attained a profile of a typical neurotic person because neurotic disorders are manifested through different symptoms. The average number of stressful events was found significantly higher in more severe forms of psoriasis compared to the milder forms. Finally, a remark has been made about benefits of a multidisciplinary approach to the study of psoriasis and the inclusion of psychotherapy in the treatment of psoriatic patients. PMID- 7862046 TI - [Evaluation of diffuse pulmonary hemorrhage with conventional radiologic methods]. AB - Diffuse lung hemorrhage is a relatively rare disorder characterized by diffuse hemorrhage from microvascular lung elements into the alveolar lumen. The disease may occur independently but is usually associated with different clinical syndromes. Regardless of the type of the syndrome it is associated with, diffuse lung hemorrhage is most frequently characterized by the following triad of clinical-radiological symptoms: hemoptysis, anemia and diffuse alveolar consolidation in the lung radiogram. The disease does not form a specific radiologic picture but encompasses a wide range of changes which can be seen in all processes characterized by the presence of the liquor in the alveolar (lung edema, pneumonia). Dynamic changes observed in the picture necessitate frequent radiologic controls which along with other clinical symptoms and the recognition of the phenomenon, might be rather valuable in setting diagnosis of the disease. PMID- 7862047 TI - [Attitudes of spouses toward examinations for the early detection of cervical and breast carcinoma]. AB - Our research program included 3474 women from Novi Sad (1957) and villages (1517) in the territory of Vojvodina. The poll investigated especially the attitudes of husbands toward the participation of their wives in check-ups for the detection of cervical and breast neoplasms. Positive attitudes toward cervical check-ups were found in 750 males from the city (54.6%) and 697 (45.9%) from the villages which represents the majority compared to those who either don't care or have no opinion of their own. More authentic relations were obtained when "negative attitudes" included also males who didn't give any answer, in that case 1206 males from the city (61.6%) and 843 from the villages (55.6%) don't encourage their wives for the detection check-ups. Similar answers were obtained to the question about breast check-ups. Positive attitude was found in 747 (54.3%) males from the city and 602 (54.1) from the villages while the number of those who either don't care or have no attitudes is smaller (628--45.7% from the city and 510--45.9% from the villages). If "negative attitudes" include those who didn't answer the question (1217--62.2% from the city and 936--61.7% from the villages) husbands who don't encourage the check-ups represent the majority. We are sure that wives' attitudes toward detection check-ups are influenced by their husbands' attitudes. Our data show that the majority of husbands' do not encourage detection check-ups negatively influencing their wives' attitudes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862048 TI - [Personal experience with the occurrence of pediatric otitis of allergic etiology in the North Backa Region]. AB - The authors report their own longtime experience with the incidence of pediatric otitis with allergic etiology. They conclude that pediatric otitis, especially the secretory type, is not always curable by the common conservative antibiotic therapy because in many cases the primary cause of the disease is not the infection but allergy. The infection in such cases is a secondary, accompanying complication. The suggestion has been supported by the statistical data. Moreover reviewed are the diagnostic methods and therapy they have applied. PMID- 7862049 TI - [Adolescent mortality in Vojvodina]. AB - The aim of the study was to determine the mortality rate of adolescents in Vojvodina and analyze the most common causes of their death. For the analysis we used the data from the Health Statistics Annual and from individual statistics reports. The observation period was between 1986 and 1988. The mean mortality rate of the adolescents in Vojvodina for that period was 6.7/100000. The leading cause of death (54.74%) was accidents (mostly traffic accidents), malignant diseases and finally cardiovascular diseases. The mortality rate was higher among older adolescents. It was 4 times higher in the outpatients compared to the inpatients and caused either by the severity of the injury and/or inadequately handled injuries. For the highest percentage of the accidents responsible were external factors among which risk behavior of the young played a significant role. The task of the society is to take appropriate measures which would reduce the role of the external factors as a cause of death. PMID- 7862050 TI - [The effect of angiotensin I converting enzyme inhibitors on renal function indicators in hypertensive patients]. AB - The paper reviews the results of a preliminary study on hemodynamic and functional kidney indices in patients with hypertension with different etiopathogenesis. The investigation was carried out in 36 patients; 30 cases with no renal artery stenosis (RAS) and 6 cases with different stages of RAS. The investigation was conducted both in basal conditions and after the peroral administration of captopril (Zorcaptil a 25 mg, 1h before the examination). Kidney hemodynamics and its function were investigated by the dynamic kidney scintigraphy with the deconvolution analysis of the renogram and by the determination of the total and separate clearances 99Tcm-MAG3 and/or 99Tcm-DTPA. The obtained results lead to the conclusion that the sensitivity of the applied methodology enables differentiation of hypertensions in whose etiopathogenesis the renin-angiotensin-aldosterone system (RAAS) does not play the key role. Further investigations are needed for valid conclusions to be made. PMID- 7862051 TI - [Etiologic structure and clinical characteristics of acute viral infections of the central nervous system with hyperproteinorachia]. AB - Clinical syndrome of acute viral meningitis and meningoencephalitis may be induced by different viruses. Etiologic diagnosis may be set by the isolation of the virus from the liquor and by the detection of specific antibodies in the blood and liquor. Our aim was to determine viral etiology of AVI with special reference to hyperproteinorachia. The study was conducted in 55 patients treated at the Clinic of Infectious Diseases in Novi Sad, with clinical picture of acute meningitis or meningoencephalitis, with pleocytosis above 50 ml in the cerebrospinal fluid. Depending on the levels of proteinorachia the patients were divided into the group with proteinorachia levels below 1g/l (34 patients) and above 1 g/l (21 patients). In the first group the most common was herpes simplex- and adenoviral etiology while in the second group most frequently found were choriolymphocytic meningitis virus (LCM) and herpes simplex virus. The protein level was in correlation with the severity of the clinical features and the duration of the treatment. PMID- 7862052 TI - [Characteristics of the human lateral geniculate nucleus vascular network]. AB - The blood supply of the lateral geniculate nucleus (LGN) was studied on ten human brains obtained at autopsy from patients of both sexes with no indication of either psychiatric and neurological disorders or trauma of CNS. The age range was form 30 to 50 years. The brain blood vessels-the basilar artery and the internal carotid artery were injected with a mixture of gelatin and Indian ink. Microdissection revealed that the arterial branches for the LGN arise from anterior choroidal artery and posterior cerebral artery through one of its central branches-lateral posterior choroidal artery. The morphology of arterial network was examined by the analysis of cleared paraffine sections. The arterial branches run in a dorsal to ventral direction of the nucleus, parallely with lines of projection and perpendicularly to the plane of the LGN laminae. Free anastomoses occur between these branches. PMID- 7862053 TI - [Histochemical features of the adrenal glomerulor zone 30 days after exposure to NPK fertilizer]. AB - Sexually mature, male, Wistar rats lived for 30 days in a workshop of an NPK artificial fertilizer factory and were subjected to the effects of different chemical matters used in the synthesis of the fertilizer. After that time period, the experimental animals were sacrificed on the same day with the control ones, in the morning hours. The histochemical characteristics of the adrenal glomerular zone were studied. The results obtained show an increased content of the following lipid substances in the cells of the glomerular zone of the experimental animals: neutral lipids, triglycerides and phospholipids. The content of nucleic acids was also changed. The quality of fat substances was altered in the experimental rats. The total appearance of the glomerular zone gives the impression of an intensified activity. PMID- 7862054 TI - Potential teratogenic and neurodevelopmental consequences of coffee and caffeine exposure: a review on human and animal data. AB - The teratogenic effect of caffeine has been clearly demonstrated in rodents. The sensitivity of different animals species is variable. Malformations have been demonstrated in mice at 50-75 mg/kg of caffeine, whereas the lowest dose usually needed to induce malformations is 80 mg/kg in rats. However, when caffeine is administered in fractioned amounts during the day, 330 mg/kg/day are necessary to reach teratogenicity in rats. In rodents, the most frequently observed malformations are those of the limbs and digits, ectrodactyly, craniofacial malformations (labial and palatal clefts) and delays in ossification of limbs, jaw and sternum. Nevertheless, even in rodents, caffeine can be considered as a weak teratogenic agent, given the quite large quantities of caffeine necessary to induce malformations and the small number of animals affected. In humans, caffeine does not present any teratogenic risk. The increased risk of the most common congenital malformations entailed by moderate consumption of caffeine is very slight. However, caffeine potentiates the teratogenic effect of other substances, such as tobacco, alcohol, and acts synergistically with ergotamine and propranolol to induce materno-fetal vasoconstrictions leading to malformations induced by ischemia. Therefore, even though caffeine does not seem to be harmful to the human fetus when intake is moderate and spread out over the day, some associations, especially with alcohol, tobacco, and vasoconstrictive or anti-migraine medications should be avoided. Maternal consumption of caffeine affects brain composition, especially in case of a low-protein diet and also seems to interfere with zinc fixation in brain. Maternal exposure to caffeine induces also long-term consequences on sleep, locomotion, learning abilities, emotivity, and anxiety in rat offspring, whereas in humans, more studies are needed to ascertain long-term behavioral effects of caffeine ingestion by pregnant mothers. PMID- 7862055 TI - A new method for evaluating air-righting reflex ontogeny in rats using prenatal exposure to phenytoin to demonstrate delayed development. AB - The air-righting reflex has been used for many years to assess reflex integrity in rodent developmental neurotoxicity investigations. However, little refinement of the technique has occurred. We describe two methodological improvements: (a) an improvement in the method of positioning rats for air-righting, and (b) a stop action photographic method to capture the rat's mid-air performance. We also compare results obtained using a visual scoring method to the newly developed photographically based scoring method. Prenatal phenytoin exposure has been shown to induce marked delays in air-righting development (14), therefore, phenytoin was used as a positive control treatment. Pregnant rats were administered 200 mg/kg phenytoin in propylene glycol or propylene glycol alone by gavage once/day on E7-18. Offspring were tested in the same apparatus twice and scored for air righting success either by direct observation or photographed and the photographs scored subsequently. Rats were administered 6 trials per day (3 trials with each method) on days 16-24 of postnatal development. Detailed analyses of the two methods included subdividing phenytoin animals into those exhibiting the neurological abnormality of circling later in life and those that did not. Both methods revealed that phenytoin animals were delayed in air-righting development compared to controls and both methods revealed that phenytoin-circlers were more impaired than phenytoin-noncirclers. Advantages of the photographic method were that it provided a more precise method of scoring and a permanent record of the animal's response. One disadvantage was that it did not distinguish groups quite as well as the visual method. PMID- 7862056 TI - Physical-chemical-activity relationship of organic solvents: effects on Na(+) K(+)-ATPase activity and membrane fluidity in mouse synaptosomes. AB - Physical-chemical-activity relationship of aromatic hydrocarbons (n = 10) and alkyl acetates (n = 16) with respect to their in vitro effects on synaptosomal membranes was studied. Na(+)-K(+)-adenosine triphosphatase (Na(+)-K(+)-ATPase) activity and membrane fluidity, which was determined using the fluorescence probe 1,6-diphenyl-1,3,5-hexatriene, were used as potential indicators of neuronal cell toxicity. The potency of inhibition for the enzyme (IC50), the potency of increasing membrane fluidity (IC12.5), and n-octanol/water partition coefficient (P) were all determined experimentally for 26 solvents. Correlation analyses were made on aromatic hydrocarbons and on alkyl acetates. There were linear relationships between log P and pIC50 (log1/IC50) values, and between log P and pIC12.5 (log1/IC12.5) values, indicating that the hydrophobicity of the solvents determines their toxic ability to affect membrane environment; the more hydrophobic the solvents are, the more toxic they are. A direct linear relationship between Na(+)-K(+)-ATPase activity pIC50 and membrane fluidity pIC12.5 values was also shown. This predictive correlation suggests a similar mechanism of membrane surface interaction govering both processes that are common to the test solvents. The present results confirm the importance of the lipid environment of neuronal membranes in maintaining the normal function of membrane bound protein. PMID- 7862057 TI - Effects of 3,3'-iminodipropionitrile on acquisition and performance of spatial tasks in rats. AB - 3,3'-Iminodipropionitrile (IDPN) has been reported to disrupt learning and memory in rats (24). The present work addressed the effects of IDPN on tasks requiring the use of spatial information. Separate groups of male rats were dosed with IDPN (IP, in 1 ml/kg saline) for 3 consecutive days and tested in the following procedures: (a) step-through passive avoidance conditioning (0, 100, 150, and 200 mg/kg/day); (b) Morris water maze (MWM) acquisition and retention (0, 125, 150, 175, and 200 mg/kg/day); (c) radial arm maze (RAM) acquisition (0, 100, 200, and 400 mg/kg/day); (d) RAM steady-state performance (0, 200, and 400 mg/kg/day); (e) repeated acquisition in the RAM (0, and 200 mg/kg/day). The vestibular toxicity of IDPN resulted in alterations in spontaneous behavior or swimming deficits in 5 of 8 rats treated with 175 mg/kg/day and in all the animals dosed with 200 or 400 mg/kg/day. IDPN increased step-through PA latencies at 200 mg/kg/day but not at lower doses. In the MWM, no performance deficits were observed at the dose levels preserving the swimming ability of the animals. In both the acquisition and the steady-state RAM tasks, IDPN (400 mg/kg/day) induced an increase in both choice errors and perseverative errors. In the RAM repeated acquisition paradigm, IDPN (200 mg/kg/day) induced performance deficits that included a decreased rate of within-session reduction in errors. The present data show that IDPN disrupts performance of tasks requiring spatial learning and memory and indicate that these deficits can be in part caused by an acquisition deficit. PMID- 7862058 TI - Augmented memory loss in aging mice after one embryonic exposure to alcohol. AB - Prenatal exposure to alcohol can produce behavioral and cognitive deficits even in the absence of dysmorphic facial features. In a mouse model, we tested whether embryonic exposure to alcohol could exacerbate functional loss as animals age. Normal-appearing offspring were selected from litters produced by C57Bl/6J mice that had been gavaged with one teratogenic dose (5.8 g/kg) of ethyl alcohol during organogenesis on the 9th day of gestation. In adulthood, the offspring suffered a deficit in long-term retention, but not acquisition, of a place learning task. Although barely detectable in young adults, the retention deficit was severe in aging mice. These findings demonstrate that the functional deficits resulting from embryonic exposure to alcohol can interact with those of aging. PMID- 7862059 TI - Symptoms indicative of the effects of organic solvent exposure in Dutch painters. AB - The report describes the results of a cross-sectional study among two groups of young and older painters and two age-matched control groups. The study was intended to gather information on the occurrence of solvent-exposure symptoms among Dutch workers using a mailed questionnaire. Results indicated that among young painters and to a lesser extent among older painters what is commonly accepted as specific symptoms and additional solvent-related symptoms showed a higher frequency than among the controls. The most interesting observation was a significant relationship between the frequency of periods of heavy exposure and the severity of most symptom categories, whereas there was a lack of consistent relationships with other exposure parameters. PMID- 7862060 TI - Effect of lead exposure on patterns of food intake in weanling rats. AB - The reduction in growth resulting from lead (PB) exposure in weanling rats is consistent with a lowering of the biological set-point for food intake. In this study the effects of lead on the patterns of food intake were examined. For 10 days (from ages 26 to 36 days), female rats were provided with drinking water containing 250 ppm lead as the acetate (n = 6) or equivalent acetate as sodium acetate (n = 6). A computerized system was used to monitor daily food intake at 5 min intervals over 10 successive 23-h periods (each period consisting of 12 h dark, 11 h light). Control rats consumed approximately 75% to 85% of their food intake during the dark phase. Exposure to lead resulted in decreased body weight, tail length, and cumulative food intake. Decreased food intake associated with lead during the first 6 days of exposure was due to a decrease in the size of each meal during the dark phase, which reflected a decrease in the duration of each meal. These results suggest that lead, at least initially, was affecting food-satiety signals to produce a premature termination of food intake during a meal. After 6 days, the lead-exposed rats appear to have adjusted their meal size and meal duration to approximately control values. However, this compensation appears to have occurred at the expense of the daily (nocturnal) number of meals, which decreased slightly (although not significantly) in lead-exposed animals. Thus, the total daily intake of food in lead-treated animals remained depressed relative to control animals. PMID- 7862061 TI - Postnatal methylazoxymethanol: sensitive periods and regional selectivity of effects. AB - Work on neonatal MAM exposure has focused primarily on exposure within the first week postpartum, and on resulting hypoplasia or stunting of the cerebellum. Rats in this study were exposed to MAM on 4 consecutive postnatal days (PND), beginning at one of six ages, from birth through weaning (PND 1, 5, 9, 13, 17, or 21). MAM was administered subcutaneously in doses of 3, 4, or 5 mg/kg twice per day. Rats were sacrificed at PNDs 28 or 84. The most sensitive age for MAM induced stunting was determined to be PNDs 1-4. When 5 mg/kg MAM was administered twice daily on PNDs 1-4, body weight was reduced by 24% at age 28 days. Additionally, when compared to control rats, brains of the 28-day-old rats were stunted as follows: whole brain (11%), cerebellum (35%), hippocampus (11%), and olfactory bulb (27%). The effects of PND 1-4 MAM exposure were still evident at 84 days of age when cerebellum and olfactory bulbs from treated rats weighed 30% less than those same regions in control rats. These findings indicate that neonatal exposure to MAM results in permanent stunting in select regions of developing rat brain. This stunting, along with other known MAM effects, can be tailored by exposure age and dose to augment the use of MAM as a positive control for investigation of compounds with neurotoxic potential. PMID- 7862062 TI - A multidisciplinary approach to neonatal ambulance design. AB - The transport of a critically ill neonate from a community hospital to a regional intensive care unit requires the expertise of a specially trained team and a transport environment that addresses the unique needs of critically ill neonates. Utilization of ground vehicles for the transportation of neonates as compared to air transport seems to be increasing on a national basis. Traditional ambulance design falls short of meeting the distinctive needs of a neonatal transport service. The purpose of this article is to describe the process used by one facility to design a neonatal-specific ambulance. Use of a multidisciplinary team in developing this vehicle helped address the identified needs of this midwestern transport service. PMID- 7862063 TI - The power in our hands: integrating developmental care into neonatal transport. AB - Research has shown that infants who receive developmentally supportive care during the course of medical treatment in the NICU have improved long-term developmental outcomes. Developmentally sound interventions should be implemented as early as possible in the hospital course and can be incorporated successfully into the care provided during transport of sick neonates. If developmental interventions are planned and implemented thoughtfully and consistently throughout the transport course, it may be possible to reduce or prevent neurodevelopmental complications. PMID- 7862064 TI - Prescheduled neonatal return transports. AB - In 1990, increasing numbers of neonatal transports and high occupancy rates of neonatal beds statewide motivated our team to take a closer look at how to provide our services more efficiently. The neonatal transport medical director and team coordinator developed a system that addressed problematic issues in providing back or return transports to the community hospitals. This system was devised, implemented, and adjusted to provide a more organized approach to the overtaxed system already in place. With efficient use of supplies, human resources, and teamwork, the prescheduled neonatal return transport process was put into effect. The system provided an easier mechanism for the coordination of return transports and helped decrease frustration levels in community hospital staff, referring nursery staff, and transport personnel. All or portions of this plan can be utilized in other neonatal transport services that find their present resources inadequate to meet the referral region's needs. PMID- 7862065 TI - Death on transport: a follow-up program. AB - St. Louis Children's Hospital has a self-contained, designated neonatal and pediatric transport team. In 1990, this team initiated a formalized death follow up program. Its purposes are to provide feedback to referring hospitals, conduct an internal review, meet quality improvement guidelines, and educate transport team members. The program differs from the traditional morbidity and mortality conference, which provides an educational and review forum only. Death follow-up meetings are held quarterly, and 61 follow-ups were done between January 1990 and December 1993. (Follow-up was done on all deaths occurring during transport as well as those occurring within 24 hours of transport). PMID- 7862066 TI - Transport pitfalls. PMID- 7862067 TI - Instrumentation in neonatal research: arterial blood pressure monitoring. PMID- 7862068 TI - Meconium aspiration syndrome. PMID- 7862069 TI - Dobutamine. PMID- 7862070 TI - The physiologic effects of air transport on the neonate. AB - As a member of a neonatal air transport team, whether fixed-wing or rotary-wing, you must have a basic understanding of flight physiology. The negative effects of altitude on the human body can be very detrimental, if not fatal, for the compromised neonate. This article looks at the physiologic stressors of air transport such as hypoxia and gas expansion. It also discusses environmental stressors such as noise, vibration, motion, temperature, and humidity. The key to successful neonatal air transport is the transport team knowing what physiologic changes to expect, properly assessing the infant, preventing stressors if able, and properly intervening as necessary. PMID- 7862071 TI - Physician leadership: directing the process of integration. PMID- 7862072 TI - Ophthalmology quiz #12. Retinal infarction due to arterial emboli. Central retinal artery emboli with "cherry red spot". PMID- 7862074 TI - Major provisions of MSMA's proposed Insurance Market Reform Bill. PMID- 7862073 TI - Physicians respond to patients' needs: Patient Fairness Act, Intractable Pain Act & Insurance Market Reform Bill. PMID- 7862075 TI - Legislative issues. Non-physician providers seeking more practice privileges. PMID- 7862077 TI - It's 6 am, do you know where your children are? PMID- 7862076 TI - Stereotactic surgery in the management of intracranial disorders. AB - Fifty-six stereotactic procedures (thirty-eight stereotactic biopsies, 13 stereotactic craniotomies, and 5 implantations of intracranial catheters) were performed on 54 patients at the University of Missouri between 1990 and 1994. In 89.5% of cases a definitive diagnosis was made by stereotactic biopsy with a major complication rate of 2.6%, rates comparable to other published series. Stereotactic craniotomy was associated with no mortality and minimal morbidity. Stereotactic surgery is a safe and effective technique that improves the management of many intracranial disorders. PMID- 7862078 TI - New report exposes trial lawyers' political clout. PMID- 7862079 TI - Exposure of passengers and flight crew to Mycobacterium tuberculosis on commercial aircraft, 1992-1995. AB - From January 1993 through February 1995, CDC and state health departments completed investigations of six instances in which passengers or flight crew traveled on commercial aircraft while infectious with tuberculosis (TB). All six of these investigations involved symptomatic TB patients with acid-fast bacillus (AFB) smear-positive cavitary pulmonary TB, who were highly infectious at the time of the flight(s). In two instances, Mycobacterium tuberculosis isolated from the index patients was resistant to both isoniazid and rifampin; organisms isolated from other cases were susceptible to all antituberculous medications. In addition, in two instances, the index patients were aware of their TB at the time of travel and were in transit to the United States to obtain medical care. However, in none of six instances were the airlines aware of the TB in these passengers. This report summarizes the investigations by CDC and state health departments and provides guidance about notification of passengers and flight crew if an exposure to TB occurs during travel on commercial aircraft. PMID- 7862080 TI - Prevention program for reducing risk for neural tube defects--South Carolina, 1992-1994. AB - Neural tube defects (NTDs) are common and serious malformations that originate early in pregnancy. In the United States, approximately 4000 pregnancies each year are affected by the two most common NTDs (spina bifida and anencephaly), and an estimated 2500 infants are born with NTDs. Based on a Public Health Service (PHS) recommendation published in September 1992, at least one half of NTDs could be prevented if all women capable of becoming pregnant consumed 0.4 mg of folic acid daily during the periconceptional period (1). Women who have previously had an NTD-affected pregnancy would especially benefit from folic acid supplements (2). In 1992, with support from a CDC cooperative agreement, the South Carolina Department of Disabilities and Special Needs implemented a prevention program to reduce the incidence of folic acid-preventable NTDs in the pregnancies of women with prior NTD-affected pregnancies. This report describes surveillance findings resulting from this program during 1992-1994. PMID- 7862081 TI - Vaccination coverage of 2-year-old children--United States, January-March, 1994. AB - The Childhood Immunization Initiative (CII) was initiated to increase vaccination coverage among 2-year-old children. The 1996 objective is to have at least 90% coverage for four of the five critical vaccines routinely recommended for children (i.e., one dose of measles-mumps-rubella vaccine [MMR] and at least three doses each of diphtheria and tetanus toxoids and pertussis vaccine [DTP], oral poliovirus vaccine, and Haemophilus influenzae type b vaccine [Hib]), and at least 70% coverage for three doses of hepatitis B vaccine (Hep B) (1). These objectives are an interim step toward the year 2000 goal of at least 90% coverage for the recommended series of vaccinations and are being monitored on an ongoing basis. This report presents national estimates of vaccination coverage among 2 year-old children derived from provisional data from the National Health Interview Survey (NHIS) for the first quarter of 1994 and compares these with the last two quarters of 1993. PMID- 7862082 TI - Use of safety belts--Madrid, Spain, 1994. AB - An estimated 300,000 persons die and 10-15 million persons are injured each year in traffic crashes throughout the world (1). In Spain, during 1993, motor-vehicle crashes accounted for 6378 deaths (16 per 100,000 population) and were the leading cause of death for persons aged 1-44 years and the leading cause of years of potential life lost (2). Safety belts are 40%-70% effective in preventing severe injuries and deaths associated with motor-vehicle crashes (3). In April 1975, the Traffic Safety Administration of Spain implemented a mandatory safety belt-use law for persons who were front-seat passengers traveling outside city limits (i.e., interurban traffic). On June 15, 1992, the law was expanded to include all front-seat passengers traveling in vehicles in the city limits and passengers in the back seats of vehicles with manufacturer-installed safety belts (4). In September 1994, the Ministry of Health of Spain, in collaboration with the Traffic Safety Administration, conducted surveys to assess the impact of the expanded law. This report summarizes findings of this assessment in Madrid, including the first direct observation survey of safety-belt use by front-seat occupants and a telephone sample survey of knowledge, attitudes, and behaviors related to motor-vehicle use. PMID- 7862083 TI - Far-red light-insensitive, phytochrome A-deficient mutants of tomato. AB - We have selected two recessive mutants of tomato with slightly longer hypocotyls than the wild type, one under low fluence rate (3 mumol/m2/s) red light (R) and the other under low fluence rate blue light. These two mutants were shown to be allelic and further analysis revealed that hypocotyl growth was totally insensitive to far-red light (FR). We propose the gene symbol fri (far-red light insensitive) for this locus and have mapped it on chromosome 10. Immunochemically detectable phytochrome A polypeptide is essentially absent in the fri mutants as is the bulk spectrophotometrically detectable labile phytochrome pool in etiolated seedlings. A phytochrome B-like polypeptide is present in normal amounts and a small stable phytochrome pool can be readily detected by spectrophotometry in the fri mutants. Inhibition of hypocotyl growth by a R pulse given every 4 h is quantitatively similar in the fri mutants and wild type and the effect is to a large extent reversible if R pulses are followed immediately by a FR pulse. After 7 days in darkness, both fri mutants and the wild type become green on transfer to white light, but after 7 days in FR, the wild-type seedlings that have expanded their cotyledons lose their capacity to green in white light, while the fri mutants de-etiolate. Adult plants of the fri mutants show retarded growth and are prone to wilting, but exhibit a normal elongation response to FR given at the end of the daily photoperiod. The inhibition of seed germination by continuous FR exhibited by the wild type is normal in the fri mutants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862084 TI - Structure and expression of the gene encoding ribosomal protein S1 from the cyanobacterium Synechococcus sp. strain PCC 6301: striking sequence similarity to the chloroplast ribosomal protein CS1. AB - We isolated a 38 kDa ssDNA-binding protein from the unicellular cyanobacterium Synechococcus sp. strain PCC 6301 and determined its N-terminal amino acid sequence. A genomic clone encoding the 38 kDa protein was isolated by using a degenerate oligonucleotide probe based on the amino acid sequence. The nucleotide sequence and predicted amino acid sequence revealed that the 38 kDa protein is 306 amino acids long and homologous to the nuclear-encoded 370 amino acid chloroplast ribosomal protein CS1 of spinach (48% identity), therefore identifying it as ribosomal protein (r-protein) S1. Cyanobacterial and chloroplast S1 proteins differ in size from Escherichia coli r-protein S1 (557 amino acids). This provides an additional evidence that cyanobacteria are closely related to chloroplasts. The Synechococcus gene rps1 encoding S1 is located 1.1 kb downstream from psbB, which encodes the photosystem II P680 chlorophyll a apoprotein. An open reading frame encoding a potential protein of 168 amino acids is present between psbB and rps1 and its deduced amino acid sequence is similar to that of E. coli hypothetical 17.2 kDa protein. Northern blot analysis showed that rps1 is transcribed as a monocistronic mRNA. PMID- 7862085 TI - Molecular cloning of mei-41, a gene that influences both somatic and germline chromosome metabolism of Drosophila melanogaster. AB - The mei-41 gene of Drosophila melanogaster plays an essential role in meiosis, in the maintenance of somatic chromosome stability, in postreplication repair and in DNA double-strand break repair. This gene has been cytogenetically localized to polytene chromosome bands 14C4-6 using available chromosomal aberrations. About 60 kb of DNA sequence has been isolated following a bidirectional chromosomal walk that extends over the cytogenetic interval 14C1-6. The breakpoints of chromosomal aberrations identified within that walk establish that the entire mei 41 gene has been cloned. Two independently derived mei-41 mutants have been shown to carry P insertions within a single 2.2 kb fragment of the walk. Since revertants of those mutants have lost the P element sequences, an essential region of the mei-41 gene is present in that fragment. A 10.5 kb genomic fragment that spans the P insertion sites has been found to restore methyl methanesulfonate resistance and female fertility of the mei-41D3 mutants. The results demonstrate that all the sequences required for the proper expression of the mei-41 gene are present on this genomic fragment. This study provides the foundation for molecular analysis of a function that is essential for chromosome stability in both the germline and somatic cells. PMID- 7862086 TI - Biosynthesis of cytochrome f in Chlamydomonas reinhardtii: analysis of the pathway in gabaculine-treated cells and in the heme attachment mutant B6. AB - Chlamydomonas reinhardtii uses two c-type cytochromes for photosynthetic electron transfer: the thylakoid membrane-bound cytochrome f of the cytochrome b6f complex and the soluble cytochrome c6. Previously, a class of photosynthesis-minus, acetate-requiring mutants was identified which were deficient in both c-type cytochromes, and biochemical analyses of cytochrome c6 biosynthesis in these strains indicated that they were each blocked at the step of heme attachment to apocytochrome c6. In order to demonstrate that the deficiency in cytochrome f results from the same biochemical and genetic defect, cytochrome f biosynthesis was examined in the B6 mutant (a representative of this phenotypic class) and in spontaneous suppressor strains derived from B6. Pulse-radiolabeling experiments show that B6 synthesizes a form of cytochrome f that is rapidly degraded in vivo. This polypeptide is membrane associated and migrates with an electrophoretic mobility identical to that of standard apocytochrome f produced in vitro but slightly greater than that of standard holocytochrome f produced in vivo by wild type cells. These findings suggest that the B6 strain is unable to convert apocytochrome f to holocytochrome f and that apocytochrome f is unstable in vivo. In the suppressed strains, accumulation of both holocytochrome f and holocytochrome c6 is restored. One suppressor mutation (strain B6R) displays uniparental inheritance whereas another (B6T3) displays Mendelian inheritance. In both cases, the three phenotypes, photosynthesis-plus, b6f+ and cyt c6+ co segregate in genetic crosses. This study therefore confirms that the dual cyt b6f /cytc6- deficiency in B6 results from a single mutation that affects a step in holocytochrome formation that is common to the biosynthetic pathways of both plastidic c-type cytochromes. The study also confirms that pre-apocytochrome f synthesis, processing and association with the membrane is not dependent on heme attachment. Synthesis of cytochrome f does, however, appear to be dependent on heme availability. In cells depleted of tetrapyrrole pathway intermediates by gabaculine treatment, cytochrome f synthesis was significantly reduced. Since gabaculine treatment did not affect the stability of cytochrome f nor the accumulation of cytochrome f-encoding transcripts, the reduction is attributed to post-transcriptional regulation of preapocytochrome f synthesis via a pathway that is sensitive to the availability of heme or a tetrapyrrole pathway intermediate. PMID- 7862087 TI - orf250 encodes a second subunit of an ABC-type heme transporter in Oenothera mitochondria. AB - A highly transcribed region in Oenothera mitochondria codes for an open reading frame comprising 250 condons (orf250). This open reading frame shows high sequence similarity to the helC gene of Rhodobacter capsulatus which encodes a subunit of a proposed ABC-type heme transporter. Transcripts of orf250 are edited by cytidine to uridine transitions at 29 sites, altering 10% of all encoded amino acids. Genes homologous to helC have also been found in the bacteria Bradyrhizobium japonicum and Escherichia coli, and are conserved in mitochondria of Marchantia polymorpha, Daucus carota, and Arabidopsis thaliana. In bacteria these genes belong to operons that are involved in the biogenesis of c-type cytochromes. The bacterial gene organization is partly conserved in Marchantia, but altered in the mitochondrial genome of Oenothera. PMID- 7862088 TI - Altered SOS induction associated with mutations in recF, recO and recR. AB - The SOS system of Escherichia coli aids survival following damage to DNA by promoting DNA repair while cell division is delayed. Induction of the SOS response is dependent on RecA and also on the product of recF. We show that normal induction also requires the products of recO and recR. SOS induction was monitored using a sfiA-lacZ fusion strain. Induction was delayed to a similar degree by mutation in recF, recO or recR. A similar effect was observed following overexpression of RecR from a recombinant recR+ plasmid. We show that the overexpression of RecR also reduces the UV resistance of a recBC sbcBC strain and of a sfiA strain, but not of a rec+sfiA+ strain. The implications of these data for the kinetics of DNA repair are discussed. PMID- 7862090 TI - Gene inactivation in the plant pathogen Glomerella cingulata: three strategies for the disruption of the pectin lyase gene pnlA. AB - The feasibility of performing routine transformation-mediated mutagenesis in Glomerella cingulata was analysed by adopting three one-step gene disruption strategies targeted at the pectin lyase gene pnlA. The efficiencies of disruption following transformation with gene replacement- or gene truncation-disruption vectors were compared. To effect replacement-disruption, G. cingulata was transformed with a vector carrying DNA from the pnlA locus in which the majority of the coding sequence had been replaced by the gene for hygromycin B resistance. Two of the five transformants investigated contained an inactivated pnlA gene (pnlA-); both also contained ectopically integrated vector sequences. The efficacy of gene disruption by transformation with two gene truncation-disruption vectors was also assessed. Both vectors carried at 5' and 3' truncated copy of the pnlA coding sequence, adjacent to the gene for hygromycin B resistance. The promoter sequences controlling the selectable marker differed in the two vectors. In one vector the homologous G. cingulata gpdA promoter controlled hygromycin B phosphotransferase expression (homologous truncation vector), whereas in the second vector promoter elements were from the Aspergillus nidulans gpdA gene (heterologous truncation vector). Following transformation with the homologous truncation vector, nine transformants were analysed by Southern hybridisation; no transformants contained a disrupted pnlA gene. Of nineteen heterologous truncation vector transformants, three contained a disrupted pnlA gene; Southern analysis revealed single integrations of vector sequence at pnlA in two of these transformants. pnlA mRNA was not detected by Northern hybridisation in pnlA- transformants. pnlA- transformants failed to produce a PNLA protein with a pI identical to one normally detected in wild-type isolates by silver and activity staining of isoelectric focussing gels. Pathogenesis on Capsicum and apple was unaffected by disruption of the pnlA gene, indicating that the corresponding gene product, PNLA, is not essential for pathogenicity. Gene disruption is a feasible method for selectively mutating defined loci in G. cingulata for functional analysis of the corresponding gene products. PMID- 7862089 TI - The possible roles of residues 79 and 80 of the Trp repressor from Escherichia coli K-12 in trp operator recognition. AB - We constructed mutants of the Trp repressor from Escherichia coli K-12 with all possible single amino acid exchanges at positions 79 and 80 (residues 1 and 2 of the recognition helix). We tested these mutants in vivo by measuring the repression of synthesis of beta-galactosidase with symmetric variants of alpha- and beta-centered trp operators, which replace the lac operator in a synthetic lac system. The Trp repressor carrying a substitution of isoleucine 79 by lysine, showed a marked specificity change with respect to base pair 7 of the alpha centered trp operator. Gel retardation experiments confirmed this result. Trp repressor mutant IR79 specifically recognizes a trp operator variant with substitutions in positions 7 and 8. Another mutant, with glycine in position 79, exhibited loss of contact at base pair 7. We speculate that the side chain of Ile79 interacts with the AT base pairs 7 and 8 of the alpha-centered trp operator, possibly with the methyl groups of thymines. Replacement of thymine in position 7 or 8 by uracil confirms the involvement of the methyl group of thymine 8 in repressor binding. Several Trp repressor mutants in position 80 (i.e. A180, AL80, AM80 and AP80) broaden the specificity of the Trp repressor for alpha centered trp operator variants with exchanges in positions 3, 4 and 5. PMID- 7862091 TI - Changes in the chromosomal insertion pattern of the copia element during the process of making chromosomes homozygous in Drosophila melanogaster. AB - In situ hybridization on polytene chromosomes of Drosophila melanogaster was used to compare the insertion patterns of copia and mdg1 transposable elements on chromosome 2 in male gametes sampled by two different methods: (i) by crossing the males tested with females from a highly inbred line with known copia and mdg1 insertion profiles; (ii) by crossing the same males with females from a marked strain, and analysing the resulting homozygous chromosomes. Crossing of the males with the inbred line led to homogeneous insertion profiles for both the copia and mdg1 elements in larvae, thus giving an accurate estimation of the patterns in the two gamete classes of each male. Crossing with the marked strain led, however, to heterogeneity in insertion patterns of the copia transposable element, while no significant polymorphism was observed for mdg1. The use of balancer chromosomes is thus not an adequate way of inferring transposable element insertion patterns of Drosophila males, at least for the copia element. This technique could, however, be powerful for investigating the control of movements of this element. PMID- 7862092 TI - Suppressors of thermosensitive mutations in the DNA polymerase delta gene of Saccharomyces cerevisiae. AB - DNA polymerases (Pol) alpha, delta and epsilon are necessary for replication of nuclear DNA. Pol delta interacts permanently or transiently with numerous accessory proteins whose identification may shed light on the function(s) of Pol delta. In vitro mutagenesis was used to induce thermosensitive (ts) mutations in the DNA polymerase delta gene (POL3). We have attempted to clone two recessive extragenic suppressors of such ts mutants (sdp1 for mutation pol3-14 and sdp5-1 for mutation pol3-11) by transforming thermoresistant haploid strains pol3-14 sdp1 and pol3-11 sdp5-1 with wild-type genomic libraries in singlecopy or multicopy vectors. None of the thermosensitive transformants so obtained was identified as being sdp1 or sdp5-1. Instead, three genes were cloned whose products interfere with the activity of suppressors. One of them is the type 1 protein phosphatase gene, DIS2. Another is a novel gene, ASM4, whose gene product is rich in asparagine and glutamine residues. PMID- 7862093 TI - Yeast proteins can activate expression through regulatory sequences of the amdS gene of Aspergillus nidulans. AB - The upstream regulatory region of the amdS gene of Aspergillus nidulans contains a CCAAT sequence known to be important in setting both basal and depressed levels of expression. We have investigated whether the CCAAT-binding HAP2/3/4 complex of the yeast Saccharomyces cerevisiae can recognise this sequence in an amdS context. Sequences from the 5' region of amdS were cloned in front of the CYC1 lacZ fusion gene bearing a minimal promoter and transformed into wild-type and hap2 strains of yeast. This study has indicated that amdS sequences are capable of promoting regulated expression of the fusion gene in response to carbon limitation. The yeast HAP2/3/4 complex can recognise the amdS CCAAT sequence and activate expression from this sequence. In addition, the results indicate that other yeast proteins can also regulate expression from the A. nidulans amdS 5'sequences under carbon-limiting conditions. PMID- 7862094 TI - Binding of integration host factor (IHF) to the Escherichia coli sodA gene and its role in the regulation of a sodA-lacZ fusion gene. AB - We used the electrophoretic mobility-shift assay to reveal specific DNA-protein interactions between DNA fragments containing the sodA promoter and proteins present in Escherichia coli cell-free extracts. We have shown specific binding of several E. coli proteins to sodA promoter sequences and identified one of these proteins as the integration host factor (IHF). Mobility-shift experiments with cell-free extracts prepared from himA (IHF-negative) mutant strains lacked a specific DNA-protein band relative to shifts made with wild-type extracts. Several potential IHF-binding sites were identified in the sodA promoter region. Purified IHF was found to bind specifically to DNA fragments containing the sodA promoter. Further evidence presented suggests that IHF binds to multiple sites in the sodA promoter. We have also investigated the transcriptional regulation of sodA by monitoring the expression of a sodA-lacZ fusion gene in an IHF-negative E. coli strain under different growth conditions. Under aerobic conditions, a deletion in himA (IHF subunit alpha) resulted in a 60% increase in sodA expression, while having no effect on induction by paraquat. The same deletion in himA did not cause derepression of sodA-lacZ during anaerobic growth, but resulted in an increased response (about twofold) to the presence of 2,2' dipyridyl compared to the isogenic wild-type strain. PMID- 7862095 TI - Cloning and expression of a cDNA copy of the viral K28 killer toxin gene in yeast. AB - The killer toxin K28, secreted by certain killer strains of the yeast Saccharomyces cerevisiae is genetically encoded by a 1.9 kb double-stranded RNA, M-dsRNA (M28), that is present within the cell as a cytoplasmically inherited virus-like particle (VLP). For stable maintenance and replication, M28-VLPs depend on a second dsRNA virus (LA), which has been shown to encode the major capsid protein (cap) and a capsid-polymerase fusion protein (cap-pol) that provides the toxin-coding M-satellites with their transcription and replicase functions. K28 toxin-coding M28-VLPs were isolated, purified and used in vitro for the synthesis of the single-stranded M28 transcript, which was shown to be of plus strand polarity and to bind to oligo(dT)-cellulose, indicating that M28(+)ssRNA contains an internal A-rich tract. Strand separation of the 1.9 kb M28-dsRNA and direct RNA sequencing of its 3' ends was performed in order to obtain specific DNA oligonucleotides that could be used as primers for cDNA synthesis. The nucleotide sequence of the toxin-coding M28-cDNA identified a single open reading frame (ORF) coding for a polypeptide of 345 amino acids, which contained two potential Kex2p/Kex1p processing sites and three potential sites for protein N-glycosylation. The toxin-coding cDNA was cloned and expressed in sensitive non-killer strains under the control of the yeast PGK promoter. Upon transformation, this construct conferred the complete K28 phenotype, demonstrating that both toxin and immunity determinants are contained within the cloned cDNA. In vitro translational analysis of the M28(+)ssRNA in vitro transcript identified the primary gene product of M28 as a K28 preprotoxin of 38 kDa (M-p38). PMID- 7862096 TI - Evidence that two zinc fingers in the methionine aminopeptidase from Saccharomyces cerevisiae are important for normal growth. AB - Limited proteolysis of intact yeast methionine aminopeptidase (MAP1) with trypsin releases a 34 kDa fragment whose NH2-terminal sequence begins at Asp70, immediately following Lys69. These results suggest that yeast MAP may have a two domain structure consisting of an NH2-terminal zinc finger domain and a C terminal catalytic domain. To test this, a mutant MAP lacking residues 2-69 was generated, overexpressed, purified and analyzed. Metal ion analyses indicate that 1 mol of wild-type yeast MAP contains 2 mol of zinc ions and at least 1 mol of cobalt ion, whereas 1 mol of the truncated MAP lacking the putative zinc fingers contains only a trace amount of zinc ions but still contains one mole of cobalt ion. These results suggest that the two zinc ions observed in the native yeast MAP are located at the Cys/His rich region and the cobalt ion is located in the catalytic domain. The kcat and Km values of the purified truncated MAP are similar to those of the wild-type MAP when measured with peptide substrates in vitro and it appears to be as active as the wild-type MAP in vivo. However, the truncated MAP is significantly less effective in rescuing the slow growth phenotype of map mutant than the wild-type MAP. These findings suggest that the zinc fingers are essential for normal MAP function in vivo, even though the in vitro enzyme assays indicate that they are not involved in catalysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862097 TI - recO and recR mutations delay induction of the SOS response in Escherichia coli. AB - RecF, RecO and RecR, three of the important proteins of the RecF pathway of recombination, are also needed for repair of DNA damage due to UV irradiation. recF mutants are not proficient in cleaving LexA repressor in vivo following DNA damage: therefore they show a delay of induction of the SOS response. In this communication, by measuring the in vivo levels of LexA repressor using anti-LexA antibodies, we show that recO and recR mutant strains are also not proficient in LexA cleavage reactions. In addition, we show that recO and recR mutations delay induction of beta-galactosidase activity expressed from a lexA-regulated promoter following exposure of cells to UV, thus further supporting the idea that recF, recO and recR gene products are needed for induction of the SOS response. PMID- 7862098 TI - Effects of N-terminal deletions of the Escherichia coli protein Fis on growth rate, tRNA(2Ser) expression and cell morphology. AB - The Escherichia coli Fis protein is known to be involved in a variety of processes, including the activation of stable RNA operons. In this paper we study the ability of a set of N-terminal Fis deletion mutants to stimulate transcription of the tRNA(2Ser) gene. The results indicate that the domain of the Fis protein containing residues 1-26 is not required for transcription activation. The Fis mutants that are still active in transcription stimulation can also complement the reduced growth rates of Fis- cells, suggesting that the same activating domain is involved in this phenomenon. In addition, we show that in fast growing cultures in the absence of an active Fis protein, minicells are formed. These minicells seem to arise from septum formation near the cell poles. Suppression of minicell formation by Fis also does not require the presence of the N-terminal domain of the protein. PMID- 7862099 TI - Tissue-specific and developmental regulation of a gene encoding a low molecular weight sulfur-rich protein in soybean seeds. AB - A gene corresponding to a cDNA clone, SE60, encoding a low molecular weight sulfur-rich protein in soybean seeds was isolated from a soybean genomic library and characterized at the nucleotide level. The SE60 gene is interrupted by an intervening sequence of 694 bp in size. The 5' flanking region of the gene contained various regulatory sequences such as the RY repeat and CACA elements found in other seed protein genes of legumes. The SE60 gene encoded a preprotein of 75 amino acids, having a signal sequence of 28 amino acids at the N-terminus. The mature protein of 47 amino acids was basic and cysteine-rich. Northern blot analysis suggested that the SE60 gene is expressed in a tissue-specific and developmentally regulated manner during soybean seed development. The SE60 genes form a small multigene family composed of about four members in the soybean genome. PMID- 7862100 TI - Ca2+ dependent activation of rat uterine glycerylphosphorylcholine diesterase: presence of a positive modulator protein in uterine secretion. AB - The rat uterine secretory enzyme glycerylphosphorylcholine (GPC) diesterase (EC 3.1.4.2) had been purified and characterized previously with respect to its mol. wt., size, amino acid, carbohydrate composition and estrogen inducible properties. This enzyme is observed to have exclusive specificity for GPC and exhibits characteristic hyperbolic kinetics with Ca2+ in an ethyleneglycolbis N'N'N'N' tetraacetic acid (EGTA) buffered system. Ca2+ reduces Km of the enzyme for GPC from 0.65 to 0.25 mM. The Km for GPC of the partially purified enzyme is found to be 0.35 mM without addition of calcium which indicates the presence of a positive modulator of the enzyme in this fraction. Based on this rationale, a protein activating factor for the enzyme was isolated from this fraction which has a native size of 18 KD as observed on Sephacryl S-200 chromatography and strikingly stimulates enzyme activity at around 0.55 microM. PMID- 7862101 TI - Carnitine palmitoyltransferase activities: effects of serum albumin, acyl-CoA binding protein and fatty acid binding protein. AB - The carnitine palmitoyltransferase activity of various subcellular preparations measured with octanoyl-CoA as substrate was markedly increased by bovine serum albumin at low microM concentrations of octanoyl-CoA. However, even a large excess (500 microM) of this acyl-CoA did not inhibit the activity of the mitochondrial outer carnitine palmitoyltransferase, a carnitine palmitoyltransferase isoform that is particularly sensitive to inhibition by low microM concentrations of palmitoyl-CoA. This bovine serum albumin stimulation was independent of the salt activation of the carnitine palmitoyltransferase activity. The effects of acyl-CoA binding protein (ACBP) and the fatty acid binding protein were also examined with palmitoyl-CoA as substrate. The results were in line with the findings of stronger binding of acyl-CoA to ACBP but showed that fatty acid binding protein also binds acyl-CoA esters. Although the effects of these proteins on the outer mitochondrial carnitine palmitoyltransferase activity and its malonyl-CoA inhibition varied with the experimental conditions, they showed that the various carnitine palmitoyltransferase preparations are effectively able to use palmitoyl-CoA bound to ACBP in a near physiological molar ratio of 1:1 as well as that bound to the fatty acid binding protein. It is suggested that the three proteins mentioned above affect the carnitine palmitoyltransferase activities not only by binding of acyl-CoAs, preventing acyl CoA inhibition, but also by facilitating the removal of the acylcarnitine product from carnitine palmitoyltransferase. These results support the possibility that the acyl-CoA binding ability of acyl-CoA binding protein and of fatty acid binding protein have a role in acyl-CoA metabolism in vivo. PMID- 7862102 TI - Catalytic roles of the AMP at the 3' end of tRNAs. AB - Recent reports suggest that the ribosome retains considerable peptidyl transferase activity even when much of the protein of the ribosome is removed and further suggests that rRNA may be the peptidyl transferase. The work here suggests that the AMP residue at the 3' terminus of each tRNA has some catalytic activity both in the esterification reaction and in forming a pseudopeptide, AcGly, and further suggests that whatever peptidyl transferase is, it finds a cooperative substrate in the aminoacyl-AMP at the 3' terminus of tRNA. PMID- 7862103 TI - The impact of type I diabetes on rat liver gamma-glutamyltranspeptidase. AB - The impact of type 1 diabetes mellitus on liver gamma-glutamyltranspeptidase, a premalignant marker, was studied. Diabetes was induced in male Sprague Dawley and Fischer 344 rats by administration of Streptozotocin, which produced a stable and moderately severe diabetic state. In liver homogenates, gamma glutamyltranspeptidase was increased over control levels: 1.2, 8.1 and 13.2 fold in Sprague-Dawley rats; 4.8, 58.4 and 84.7 fold in Fischer 344 rats; at 1, 3 and 6 weeks following Streptozotocin treatment. In plasma membranes isolated from the livers of Fischer 344 rats, gamma-glutamyltranspeptidase was increased over control levels: 5.6, 75 and 127 fold at weeks 1, 3 and 6 following Streptozotocin treatment. The relative specific activity of 5'-nucleotidase was found to be similar: 9-14, indicating comparable degrees of plasma membrane purity. Plasma glutamate-pyruvate transaminase levels were minimally and similarly affected at all time points indicating lack of association of increasing gamma glutamyltranspeptidase activity with overt liver damage. Thyroid hormone replacement, with both T3 (0.6 micrograms/Kg) once a day and T4 (6.0 micrograms/kg) twice a day for three days elicited a further 30% increment in enzyme activity. Insulin replacement (20-40 units/200 g body weight) twice a day for five days reduced enzyme activity 51% at week 6. This was associated with an increase in gamma-glutamyltranspeptidase in the plasma from 14 fold over control levels in the diabetic state at week 6 to 53 fold over control levels after insulin replacement at week 6. It is proposed that the diabetes-induced increase in gamma-glutamyltranspeptidase is reduced by an insulin-directed shedding of the enzyme into the plasma. PMID- 7862104 TI - Leukotoxin, a linoleate epoxide: its implication in the late death of patients with extensive burns. AB - Burn death based on circulatory shock is often encountered after recovery from primary shock in patients with deep and extensive burns, i.e., late death. Several toxic substances have been proposed, however, the responsible substance remains obscure. Since we have found leukotoxin, a highly cytotoxic linoleate epoxide biosynthesized by neutrophils, in the burned skin, in the present study we determined plasma leukotoxin concentrations in various degree of 30 burn patients. C-reactive protein and circulatory white blood cells were also measured. A significantly high mortality rate of patients with extensive burns (burn surface area over 70%) was observed compared with that in patients with burn surface area under 70%, and significantly high leukotoxin concentrations were observed within a week, and 3 weeks after the thermal injury in patients with extensive burns compared with those in patients with burn surface area under 70%. There were two peaks of plasma leukotoxin concentrations, i.e., the early phase (within 1 week) and the late phase (over 1 week) in patients with extensive burns. Plasma leukotoxin concentrations significantly correlated with burn surface area in the early phase, and similar correlations were observed in the late phase. A significantly high mortality rate (61%) of patients with peak leukotoxin concentrations over 30 nmol/ml was observed compared with 8% for those below 30 nmol/ml. Plasma leukotoxin concentration correlated significantly to C reactive protein concentration, log (leukotoxin nmol/ml) = 0.042 x C-reactive protein (mg/dl) + 0.74, (r = 0.83, P < 0.01) in the late phase. From these results, it is concluded that leukotoxin is produced in patients with burns particularly in the late phase of extensive burns, and leukotoxin might play an important role in the tissue destructive procedure associated with severe burns. PMID- 7862105 TI - The choice of resuspension medium for isolated rat liver nuclei: effects on nuclear morphology and in vitro transcription. AB - Standard protocols for in vitro transcription assay (nuclear run-off) include 10 40% (v/v) glycerol (of various ionic strength) in the medium used for resuspension/storage of the isolated nuclei. In the present work the morphological and functional properties of nuclei isolated from rat liver have been studied as a function of the content of glycerol, sucrose and inorganic ions (K+ and Mg2+) in the resuspension medium. In contrast to earlier reports, glycerol was found not to be essential to maintain morphological integrity and RNA polymerase activity in frozen/stored nuclei. Nuclear pellets, resuspended and stored in isoosmotic sucrose media, were found to give morphologically intact and transcriptionally active nuclei. Furthermore, these nuclei displayed a higher specific hybridization signal for the differentially expressed genes encoding peroxisomal beta-oxidation enzymes, relative to the total RNA synthesis, than nuclei resuspended and stored in a hyperosmotic glycerol-containing medium. The concentrations of inorganic ions were also found to affect nuclear morphology. Flow cytometry indicated DNA leakage from nuclei at insufficient concentrations of K+ and Mg2+, and high ionic strength favoured aggregation and disintegration of nuclei. Our findings indicate that quantitative results from nuclear run-off experiments should be interpreted with caution until the process of transcription in isolated nuclei is better understood. PMID- 7862106 TI - Expression and characterization of a Dictyostelium discoideum annexin. AB - The annexins are calcium-dependent phospholipid-binding proteins. Recently the gene encoding the homologue of a mammalian annexin has been identified in Dictyostelium discoideum. Analysis of cDNA and genomic clones showed that the transcript for Dictyostelium annexin is alternatively spliced (Greenwood, M. and Tsang, A. (1991) Biochim. Biophys. Acta 1088, 429-432; Doring, V., Schleicher, M and Noegel, A. (1991) J. Biol. Chem. 266, 17509-17515). Here, we showed that the Dictyostelium annexin DNA hybridized to two populations of transcripts. We used a recombinant annexin polypeptide to raise polyclonal antibody. Immunoblot analysis revealed that the antibody recognized two polypeptides of 48 kDa and 54 kDa in developing D. discoideum cells. The molecular sizes of these polypeptides correspond well with the expected sizes of the alternatively spliced products. The 48-kDa and 54-kDa polypeptides were purified by isoelectric focusing to more than 70% homogeneity. The partially purified proteins were found to associate with phosphatidylserine vesicles in a calcium-dependent manner. These results suggest that the 48- and 54-kDa polypeptides are the products of alternative splicing of the annexin transcripts. During development the two polypeptides accumulate at different rates to about 60 times the level detected in vegetative cells. On the other hand, RNA blot analysis showed that the level of the annexin transcripts in multicellular aggregates was about 5 times that of vegetative cells. PMID- 7862107 TI - Cytochalisin D exerts stimulatory and inhibitory effects on insulin-induced glucokinase mRNA expression in hepatocytes. AB - The microfilament cytoskeleton is postulated to have a role in the localization, transport and anchorage of certain specific mRNAs. We investigated the effects of cytochalasin D, a fungal metabolite that binds to actin and disrupts the microfilament structure, on insulin-induced expression of glucokinase mRNA in rat hepatocyte cultures. Cytochalasin-D significantly potentiates insulin-induced glucokinase mRNA expression at 100 nM concentration but counteracts glucokinase expression at 2-20 microM. The latter effect is at least in part due to an increase in glucokinase mRNA degradation. This effect of cytochalasin D cannot be accounted for by an increase in cAMP and is also not due to a non-specific effect on mRNA degradation since albumin mRNA levels were not affected by cytochalasin-D and actin mRNA and tubulin mRNA levels were increased. Measurement of glucokinase mRNA release from digitonin-permeabilized hepatocytes suggests that cytochalasin D does not cause acute dissociation of glucokinase mRNA from its binding site. The increased degradation of glucokinase mRNA suggests involvement of the cytoskeleton in glucokinase mRNA stability. However, an additional effect of cytochalasin D on the insulin signalling mechanism cannot be excluded. PMID- 7862108 TI - Identification and characterization of a putative telomere end-binding protein from Tetrahymena thermophila. AB - Telomeric DNA of Tetrahymena thermophila consists of a long stretch of (TTGGGG)n double-stranded repeats with a single-stranded (TTGGGG)2 3' overhang at the end of the chromosome. We have identified and characterized a protein that specifically binds to a synthetic telomeric substrate consisting of duplex DNA and the 3' telomeric repeat overhang. This protein is called TEP (telomere end binding protein). A change from G to A in the third position of the TTGGGG overhang repeat converts the substrate to a human telomere analog and reduces the binding affinity approximately threefold. Changing two G's to C's in the TTGGGG repeats totally abolishes binding. However, permutation of the Tetrahymena repeat sequence has only a minor effect on binding. A duplex structure adjacent to the 3' overhang is required for binding, although the duplex need not contain telomeric repeats. TEP does not bind to G-quartet DNA, which is formed by many G rich sequences. TEP has a greatly reduced affinity for RNA substrates. The copy number of TEP is at least 2 x 10(4) per cell, and it is present under different conditions of cell growth and development, although its level varies. UV cross linking experiments show that TEP has an apparent molecular mass of approximately 65 kDa. Unlike other telomere end-binding proteins, TEP is sensitive to high salt concentrations. PMID- 7862109 TI - Natural vitamin D3 response elements formed by inverted palindromes: polarity directed ligand sensitivity of vitamin D3 receptor-retinoid X receptor heterodimer-mediated transactivation. AB - VDR, the nuclear receptor for 1,25-dihydroxyvitamin D3 (VD), is a member of the superfamily of nuclear hormone receptors and controls multiple aspects of homeostasis, cell growth, and differentiation. VDR can function as a homodimer, but heterodimerization with the retinoid X receptor (RXR), retinoic acid receptor, or thyroid hormone receptor increases its affinity for response elements in the promoter of target genes. All natural VD response elements identified so far consist of direct repeats of a variety of hexameric core binding motifs with a preferential spacing of three nucleotides (DR3s). However, all four VD signalling pathways function also on response elements formed by inverted palindromes, although these sequences were not of natural origin. Here, we report the identification of two VD response elements consisting of inverted palindromes spaced by nine nucleotides (IP9s) in the promoters of the human calbindin D9k gene and the rat osteocalcin gene. Like most DR3-type VD response elements, both IP9s are preferentially bound by VDR-RXR heterodimers with a 5' RXR-VDR-3' polarity, whose transcriptional activity can be enhanced by costimulation with 9-cis retinoic acid. We demonstrate that changing the response element orientation relatively to the basal promoter decreases the sensitivity of transcriptional activation by VD by about 10-fold. Our findings indicate that inverted palindromes are as functional as direct repeats. Furthermore, we suggest that the orientation of a nuclear receptor complex in relation to the basic transcriptional machinery, which is directed by heterodimer polarity and response element orientation, influences the ligand sensitivity of the respective target gene expression. PMID- 7862110 TI - Thyrotropin-induced mitogenesis is Ras dependent but appears to bypass the Raf dependent cytoplasmic kinase cascade. AB - Cellular growth control requires the coordination and integration of multiple signaling pathways which are likely to be activated concomitantly. Mitogenic signaling initiated by thyrotropin (TSH) in thyroid cells seems to require two distinct signaling pathways, a cyclic AMP (cAMP)-dependent signaling pathway and a Ras-dependent pathway. This is a paradox, since activated cAMP-dependent protein kinase disrupts Ras-dependent signaling induced by growth factors such as epidermal growth factor and platelet-derived growth factor. This inhibition may occur by preventing Raf-1 protein kinase from binding to Ras, an event thought to be necessary for the activation of Raf-1 and the subsequent activation of the mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinases (MEKs) and MAP kinase (MAPK)/ERKs. Here we report that serum-stimulated hyperphosphorylation of Raf-1 was inhibited by TSH treatment of Wistar rat thyroid cells, indicating that in this cell line, as in other cell types, increases in intracellular cAMP levels inhibit activation of downstream kinases targeted by Ras. Ras-stimulated expression of genes containing AP-1 promoter elements was similarly inhibited by TSH. On the other hand, stimulation of thyroid cells with TSH resulted in stimulation of DNA synthesis which was Ras dependent but both Raf-1 and MEK independent. We also show that Ras-stimulated DNA synthesis required the use of this kinase cascade in untreated quiescent cells but not in TSH-treated cells. These data suggest that in TSH-treated thyroid cells, Ras might be able to signal through effectors other than the well studied cytoplasmic kinase cascade. PMID- 7862111 TI - Binding of NCK to SOS and activation of ras-dependent gene expression. AB - NCK, an SH2- and SH3 domain-containing protein, becomes phosphorylated and associated with tyrosine kinase receptors upon growth factor stimulation. The sequence of NCK suggests that NCK functions as a linker between receptors and a downstream signaling molecule. To determine if NCK can mediate growth factor stimulated responses, we measured the ability of NCK to activate the fos promoter. We found that in NIH 3T3 cells, NCK strongly activates this promoter. The effect of NCK on the fos promoter is enhanced by c-ras and blocked by dominant negative ras. We also found that NCK binds directly to the guanine nucleotide exchange factor SOS. This interaction is mediated by the SH3 domains of NCK. These findings suggest that NCK can regulate p21ras-dependent gene transcription through interaction with SOS protein. PMID- 7862112 TI - Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the beta catenin gene in a human cancer cell line, HSC-39. AB - Detachment of cell-cell adhesion is indispensable for the first step of invasion and metastasis of cancer. This mechanism is frequently associated with the impairment of either E-cadherin expression or function. However, mechanisms of such abnormalities have not been fully elucidated. In this study, we demonstrated that the function of E-cadherin was completely abolished in the human gastric cancer cell line HSC-39, despite the high expression of E-cadherin, because of mutations in one of the E-cadherin-associated cytoplasmic proteins, beta-catenin. Although immunofluorescence staining of HSC-39 cells by using an anti-E-cadherin antibody (HECD-1) revealed the strong and uniform expression of E-cadherin on the cell surface, cell compaction and cell aggregation were not observed in this cell. Western blotting (immunoblotting) using HECD-1 exhibited a 120-kDa band which is equivalent to normal E-cadherin. Northern (RNA) blotting demonstrated a 4.7-kb band, the same as mature E-cadherin mRNA. Immunoprecipitation of metabolically labeled proteins with HECD-1 revealed three bands corresponding to E-cadherin, alpha-catenin, and gamma-catenin and a 79-kDa band which was apparently smaller than that of normal beta-catenin, indicating truncated beta catenin. The 79-kDa band was immunologically identified as beta-catenin by using immunoblotting with anti-beta-catenin antibodies. Examination of beta-catenin mRNA by the reverse transcriptase-PCR method revealed a transcript which was shorter than that of normal beta-catenin. The sequencing of PCR product for beta catenin confirmed deletion in 321 bases from nucleotides +82 to +402. Southern blotting of beta-catenin DNA disclosed mutation at the genomic level. Expression vectors of Beta-catenin were introduced into HSC-39 cells by transfection. In the obtained transfectants, E-cadherin-dependent cell-cell adhesiveness was recovered, as revealed by cell compaction, cell aggregation, and immunoflourescence staining. From these results, it was concluded that in HSC-39 cells, impaired cell-cell adhesion is due to mutations in beta-catenin which results in the dysfunction of E-cadherin. PMID- 7862113 TI - Autoregulation of the human C/EBP alpha gene by stimulation of upstream stimulatory factor binding. AB - The human C/EBP alpha gene promoter shares significant sequence homology with that of the mouse but has a different mechanism of autoregulation. Activation of the murine promoter by direct binding of C/EBP alpha to a site within 200 bp of the transcriptional start was shown to elevate activity by approximately threefold (R. J. Christy, K. H. Kaestner, D. E. Geiman, and M. D. Lane, Proc. Natl. Acad. Sci. USA 88:2593-2597, 1991; K. Legraverend, P. Antonson, P. Flodby, and K. G. Xanthapoulos, Nucleic Acids Res. 21:1735-1742, 1993). Unlike its murine counterpart, the human C/EBP alpha gene promoter does not contain a cis element that binds the C/EBP alpha protein. Neither C/EBP alpha nor C/EBP beta (NF-Il-6) binds the human C/EBP alpha promoter within 437 bp. However, cotransfection studies show that C/EBP alpha stimulates transcription of a reporter gene driven by 437 bp of the C/EBP alpha promoter. Our studies show that the human C/EBP alpha protein stimulates USF to bind to a USF consensus element within C/EBP alpha promoter and activates it by two- to threefold. We propose that the human gene employs the ubiquitously expressed DNA-binding protein factor USF to carry out autoregulation. Autoregulation of the human C/EBP alpha promoter was abolished by deletion of the USF binding site, CACGTG. Expression of human C/EBP beta following transfection did not stimulate USF binding. These studies suggest a mechanism whereby tissue-specific autoregulation can be achieved via a trans acting factor that is expressed in all cell types. Thus, direct binding of the C/EBP alpha protein to the promoter of the C/EBP alpha gene is not required for autoregulation. PMID- 7862114 TI - ADA3, a putative transcriptional adaptor, consists of two separable domains and interacts with ADA2 and GCN5 in a trimeric complex. AB - Mutations in yeast ADA2, ADA3, and GCN5 weaken the activation potential of a subset of acidic activation domains. In this report, we show that their gene products form a heterotrimeric complex in vitro, with ADA2 as the linchpin holding ADA3 and GCN5 together. Further, activation by LexA-ADA3 fusions in vivo are regulated by the levels of ADA2. Combined with a prior observation that LexA ADA2 fusions are regulated by the levels of ADA3 (N. Silverman, J. Agapite, and L. Guarente, Proc. Natl. Acad. Sci. USA 91:11665-11668, 1994), this finding suggests that these proteins also form a complex in cells. ADA3 can be separated into two nonoverlapping domains, an amino-terminal domain and a carboxyl-terminal domain, which do not separately complement the slow-growth phenotype or transcriptional defect of a delta ada3 strain but together supply full complementation. The carboxyl-terminal domain of ADA3 alone suffices for heterotrimeric complex formation in vitro and activation of LexA-ADA2 in vivo. We present a model depicting the ADA complex as a coactivator in which the ADA3 amino-terminal domain mediates an interaction between activation domains and the ADA complex. PMID- 7862115 TI - Novel CDC34 (UBC3) ubiquitin-conjugating enzyme mutants obtained by charge-to alanine scanning mutagenesis. AB - CDC34 (UBC3) encodes a ubiquitin-conjugating (E2) enzyme required for transition from the G1 phase to the S phase of the budding yeast cell cycle. CDC34 consists of a 170-residue catalytic N-terminal domain onto which is appended an acidic C terminal domain. A portable determinant of cell cycle function resides in the C terminal domain, but determinants for specific function must reside in the N terminal domain as well. We have explored the utility of "charge-to-alanine" scanning mutagenesis to identify novel N-terminal domain mutants of CDC34 that are enzymatically competent with respect to unfacilitated (E3-independent) ubiquitination but that nevertheless are defective with respect to its cell cycle function. Such mutants may reveal determinants of specific in vivo function, such as those required for interaction with substrates or trans-acting regulators of activity and substrate selectivity. Three of 18 "single-scan" mutants (in which small clusters of charged residues were mutated to alanine) were compromised with respect to in vivo function. One mutant (cdc34-109, 111, 113A) targeted a 12 residue segment of the Cdc34 protein not found in most other E2s and was unable to complement a cdc34 null mutant at low copy numbers but could complement a null mutant when overexpressed from an induced GAL1 promoter. Combining adjacent pairs of single-scan mutants to produce "double-scan" mutants yielded four additional mutants, two of which showed heat and cold sensitivity conditional defects. Most of the mutant proteins expressed in Escheria coli displayed unfacilitated (E3 independent) ubiquitin-conjugating activity, but two mutants differed from wild type and other mutant Cdc34 proteins in the extent of multiubiquitination they catalyzed during an autoubiquitination reation-conjugating enzyme function and have identified additional mutant alleles of CDC34 that will be valuable in further genetic and biochemical studies of Cdc34-dependent ubiquitination. PMID- 7862116 TI - The transcriptional activator GCN4 contains multiple activation domains that are critically dependent on hydrophobic amino acids. AB - GCN4 is a transcriptional activator in the bZIP family that regulates amino acid biosynthetic genes in the yeast Saccharomyces cerevisiae. Previous work suggested that the principal activation domain of GCN4 is a highly acidic segment of approximately 40 amino acids located in the center of the protein. We conducted a mutational analysis of GCN4 with a single-copy allele expressed under the control of the native promoter and translational control elements. Our results indicate that GCN4 contains two activation domains of similar potency that can function independently to promote high-level transcription of the target genes HIS3 and HIS4. One of these domains is coincident with the acidic activation domain defined previously; the other extends over the N-terminal one-third of the protein. Both domains are partially dependent on the coactivator protein ADA2. Each domain appears to be composed of two or more small subdomains that have additive effects on transcription and that can cooperate in different combinations to promote high-level expression of HIS3 and HIS4. At least three of these subdomains are critically dependent on bulky hydrophobic amino acids for their function. Five of the important hydrophobic residues, Phe-97, Phe-98, Met 107, Tyr-110, and Leu-113, fall within a region of proposed sequence homology between GCN4 and the herpesvirus acidic activator VP16. The remaining three residues, Trp-120, Leu-123, and Phe-124, are highly conserved between GCN4 and its Neurospora counterpart, cpc-1. Because of the functional redundancy in the activation domain, mutations at positions 97 and 98 must be combined with mutations at positions 120 to 124 to observe a substantial reduction in activation by full-length GCN4, and substitution of all eight hydrophobic residues was required to inactivate full-length GCN4. These hydrophobic residues may mediate important interactions between GCN4 and one or more of its target proteins in the transcription initiation complex. PMID- 7862117 TI - Analysis of the yeast transcription factor TFIIA: distinct functional regions and a polymerase II-specific role in basal and activated transcription. AB - To probe the structure and function of the Saccharomyces cerevisiae general transcription factor TFIIA, we have systematically mutagenized the genes encoding both subunits and analyzed the effects of the mutations both in vivo and in vitro. We found that the central nonconserved region of the large subunit is not essential for function and likely acts as a spacer between the conserved N- and C terminal regions. Deletion mutagenesis of the large subunit defined a region which is required for TATA binding protein (TBP) interaction. Alanine scanning mutagenesis defined a cluster of four basic residues which are likely required for interaction with DNA in the TBP-DNA complex. Much of the conserved regions of both subunits is required for subunit association, suggesting that these conserved regions fold into compact domains which extensively interact. In vitro transcription performed with extracts from yeast strains with mutations in either the large or the small TFIIA subunit demonstrated that TFIIA stimulates both basal and activated polymerase II (Pol II) transcription. The TFIIA-depleted extracts have normal Pol I and Pol III transcription activity, showing that TFIIA is a Pol II-specific factor. In vivo depletion of TFIIA activity reduced transcription from four different Pol II promoters. Finally, alanine scanning mutagenesis of TFIIA's small subunit has identified at least one mutation which is defective in transcription but which is not defective in subunit association or binding to TBP or TBP-DNA complexes. PMID- 7862118 TI - Repression of platelet-derived growth factor beta-receptor expression by mitogenic growth factors and transforming oncogenes in murine 3T3 fibroblasts. AB - Platelet-derived growth factor BB (PDGF-BB) is an important extracellular factor for regulating the G0-S phase transition of murine BALB/c-3T3 fibroblasts. We have investigated the expression of the PDGF beta receptor (PDGF beta R) in these cells. We show that the state of growth arrest in G0, resulting from serum deprivation, is associated with increased expression of the PDGF beta R. When the growth-arrested fibroblasts are stimulated to reenter the cell cycle by the mitogenic action of serum or certain specific combinations of growth factors, PDGF beta R mRNA levels and cell surface PDGF-BB-binding sites are markedly downregualted. Oncogene-transformed 3T3 cell lines, which fail to undergo growth arrest following prolonged serum deprivation, express constitutively low levels of the PDGF beta R mRNA and possess greatly reduced numbers of cell surface PDGF receptors, as determined by PDGF-BB binding and Western blotting (immunoblotting). Nuclear runoff assays indicate the mechanism of repression of PDGF beta R expression to be, at least in large part, transcriptional. These data indicate that expression of the PDGF beta R is regulated in a growth state dependent manner in fibroblasts and suggest that this may provide a means by which cells can modulate their responsiveness to the actions of PDGF. PMID- 7862119 TI - The embryonic enhancer-binding protein SSAP contains a novel DNA-binding domain which has homology to several RNA-binding proteins. AB - Stage-specific activator protein (SSAP) is a 43-kDa polypeptide that binds to an enhancer element of the sea urchin late histone H1 gene. This enhancer element mediates the transcriptional activation of the late histone H1 gene in a temporally specific manner at the mid-blastula stage of embryogenesis. We have cloned cDNAs encoding SSAP by using polyclonal antibodies raised against purified SSAP to screen expression libraries. SSAP is unrelated to previously characterized transcription factors; however, it exhibits striking homology to a large family of proteins involved in RNA processing. The protein is a sequence specific DNA-binding protein that recognizes both single- and double-stranded DNA. The DNA-binding domain of the protein was localized to the conserved RNA recognition motif (RRM). In addition to tandem copies of this conserved domain, SSAP contains a central domain that is rich in glutamine and glycine and a C terminal domain that is enriched in serine, threonine, and basic amino acids. Overexpression of SSAP in sea urchin embryos by microinjection of either synthetic mRNA or an SSAP expression vector results in four- to eightfold transactivation of target reporter genes that contain the enhancer sequence. Transactivation occurs beginning only at the mid-blastula stage of development, suggesting that SSAP must be modified in a stage-specific manner in order to activate transcription. In addition, there are a number of other RRM-containing proteins that contain glutamine-rich regions which are postulated to function in the regulation of RNA processing. Instead, we suggest that SSAP is a member of a family of glutamine-rich RRM proteins which constitute a novel class of transcription factors. PMID- 7862120 TI - A ubiquitin mutant with specific defects in DNA repair and multiubiquitination. AB - The degradation of many proteins involves the sequential ligation of ubiquitin molecules to the substrate to form a multiubiquitin chain linked through Lys-48 of ubiquitin. To test for the existence of alternate forms of multiubiquitin chains, we examined the effects of individually substituting each of six other Lys residues in ubiquitin with Arg. Substitution of Lys-63 resulted in the disappearance of a family of abundant multiubiquitin-protein conjugates. The UbK63R mutants were not generally impaired in ubiquitination, because they grew at a wild-type rate, were fully proficient in the turnover of a variety of short lived proteins, and exhibited normal levels of many ubiquitin-protein conjugates. The UbK63R mutation also conferred sensitivity to the DNA-damaging agents methyl methanesulfonate and UV as well as a deficiency in DNA damage-induced mutagenesis. Induced mutagenesis is mediated by a repair pathway that requires Rad6 (Ubc2), a ubiquitin-conjugating enzyme. Thus, the UbK63R mutant appears to be deficient in the Rad6 pathway of DNA repair. However, the UbK63R mutation behaves as a partial suppressor of a rad6 deletion mutation, indicating that an effect of UbK63R on repair can be manifest in the absence of the Rad6 gene product. The UbK63R mutation may therefore define a new role of ubiquitin in DNA repair. The results of this study suggest that Lys-63 is used as a linkage site in the formation of novel multiubiquitin chain structures that play an important role in DNA repair. PMID- 7862121 TI - Mutational analysis of Saccharomyces cerevisiae U4 small nuclear RNA identifies functionally important domains. AB - U4 small nuclear RNA (snRNA) is essential for pre-mRNA splicing, although its role is not yet clear. On the basis of a model structure (C. Guthrie and B. Patterson, Annu. Rev. Genet. 22:387-419, 1988), the molecule can be thought of as having six domains: stem II, 5' stem-loop, stem I, central region, 3' stem-loop, and 3'-terminal region. We have carried out extensive mutagenesis of the yeast U4 snRNA gene (SNR14) and have obtained information on the effect of mutations at 105 of its 160 nucleotides. Fifteen critical residues in the U4 snRNA have been identified in four domains: stem II, the 5' stem-loop, stem I, and the 3' terminal region. These domains have been shown previously to be insensitive to oligonucleotide-directed RNase H cleavage (Y. Xu, S. Petersen-Bjorn, and J. D. Friesen, Mol. Cell. Biol. 10:1217-1225, 1990), suggesting that they are involved in intra- or intermolecular interactions. Stem II, a region that base pairs with U6 snRNA, is the most sensitive to mutation of all U4 snRNA domains. In contrast, stem I is surprisingly insensitive to mutational change, which brings into question its role in base pairing with U6 snRNA. All mutations in the putative Sm site of U4 snRNA yield a lethal or conditional-lethal phenotype, indicating that this region is important functionally. Only two nucleotides in the 5' stem-loop are sensitive to mutation; most of this domain can tolerate point mutations or small deletions. The 3' stem-loop, while essential, is very tolerant of change. A large portion of the central domain can be removed or expanded with only minor effects on phenotype, suggesting that it has little function of its own. Analysis of conditional mutations in stem II and stem I indicates that although these single-base changes do not have a dramatic effect on U4 snRNA stability, they are defective in RNA splicing in vivo and in vitro, as well as in spliceosome assembly. These results are discussed in the context of current knowledge of the interactions involving U4 snRNA. PMID- 7862122 TI - The human leukemia oncogene bcr-abl abrogates the anchorage requirement but not the growth factor requirement for proliferation. AB - Proliferation of normal cells in a multicellular organism requires not only growth factors but also the proper attachment to the extracellular matrix. A hallmark of neoplastic transformation is the loss of anchorage dependence which usually accompanies the loss of growth factor requirement. The Bcr-Abl tyrosine kinase of human leukemias is shown here to abrogate only the anchorage, not the growth factor, requirement. Bcr-Abl-transformed cells grow in soft agar but do not proliferate in serum-free media. Bcr-Abl does not activate the mitogenic pathway, as indicated by its inability to induce enhancers such as the serum response element or the tetradecanoyl phorbol acetate response element (TRE). However, Bcr-Abl can alleviate the anchorage requirement for the induction of the TRE enhancer; i.e., it allows serum to activate the TRE in detached cells. This activity is dependent on the association of an active Bcr-Abl tyrosine kinase with the actin filaments. Despite its association with the adapter protein Grb2, Bcr-Abl's effect on the TRE enhancer is not blocked by dominant negative Ras or Raf. The finding that Bcr-Abl tyrosine kinase abrogates only anchorage dependence may have important implications on the pathogenesis of chronic myelogenous leukemia. PMID- 7862123 TI - In vivo stimulation of I kappa B phosphorylation is not sufficient to activate NF kappa B. AB - NF-kappa B is a major inducible transcription factor in many immune and inflammatory reactions. Its activation involves the dissociation of the inhibitory subunit I kappa B from cytoplasmic NF-kappa B/Rel complexes, following which the Rel proteins are translocated to the nucleus, where they bind to DNA and activate transcription. Phosphorylation of I kappa B in cell-free experiments results in its inactivation and release from the Rel complex, but in vivo NF kappa B activation is associated with I kappa B degradation. In vivo phosphorylation of I kappa B alpha was demonstrated in several recent studies, but its role is unknown. Our study shows that the T-cell activation results in rapid phosphorylation of I kappa B alpha and that this event is a physiological one, dependent on appropriate lymphocyte costimulation. Inducible I kappa B alpha phosphorylation was abolished by several distinct NF-kappa B blocking reagents, suggesting that it plays an essential role in the activation process. However, the in vivo induction of I kappa B alpha phosphorylation did not cause the inhibitory subunit to dissociate from the Rel complex. We identified several protease inhibitors which allow phosphorylation of I kappa B alpha but prevent its degradation upon cell stimulation, presumably through inhibition of the cytoplasmic proteasome. In the presence of these inhibitors, phosphorylated I kappa B alpha remained bound to the Rel complex in the cytoplasm for an extended period of time, whereas NF-kappa B activation was abolished. It appears that activation of NF-kappa B requires degradation of I kappa B alpha while it is a part of the Rel cytoplasmic complex, with inducible phosphorylation of the inhibitory subunit influencing the rate of degradation. PMID- 7862124 TI - Phosphorylation of I kappa B alpha precedes but is not sufficient for its dissociation from NF-kappa B. AB - NF-kappa B is an important activator of immune and inflammatory response genes. NF-kappa B is sequestered in the cytoplasm of nonstimulated cells through interaction with the I kappa B inhibitors. These inactive complexes are dissociated in response to a variety of extracellular signals, thereby allowing free NF-kappa B dimers to translocate to the nucleus and active transcription of specific target genes. The current dogma is that phosphorylation of the I kappa Bs is responsible for dissociation of the inactive complexes, an event that is rendered irreversible by rapid I kappa B degradation. Here, we show that inducers of NF-kappa B activity stimulate the hyperphosphorylation of one of the I kappa Bs, I kappa B alpha. However, contrary to the present dogma the hyperphosphorylated form of I kappa B alpha remains associated with NF-kappa B components such as RelA (p65). Thus, phosphorylation of I kappa B alpha is not sufficient to cause dissociation of the inactive NF-kappa B:I kappa B alpha complex. However, that complex is disrupted through the selective degradation of phosphorylated I kappa B alpha in response to extracellular signals. Using a variety of protease inhibitors, some of which have specificity towards the multicatalytic proteinase complex, we demonstrate that degradation of I kappa B alpha is required for NF-kappa B activation. The results of these experiments are more consistent with a new model according to which phosphorylation of I kappa B alpha associated with NF-kappa B marks it for proteolytic degradation. I kappa B alpha is degraded while bound to NF-kappa B. The selective degradation of I kappa B alpha releases active NF-kappa B dimers which can translocate to the nucleus to activate specific target genes. PMID- 7862125 TI - A human protein selected for interference with Ras function interacts directly with Ras and competes with Raf1. AB - The overexpression of some human proteins can cause interference with the Ras signal transduction pathway in the yeast Saccharomyces cerevisiae. The functional block is located at the level of the effector itself, since these proteins do not suppress activating mutations further downstream in the same pathway. We now demonstrate, with in vivo and in vitro experiments, that the protein encoded by one human cDNA (clone 99) can interact directly with yeast Ras2p and with human H Ras protein, and we have named this gene rin1 (Ras interaction/interference). The interaction between Ras and Rin1 is enhanced when Ras is bound to GTP. Rin1 is not able to interact with either an effector mutant or a dominant negative mutant of H-Ras. Thus, Rin1 displays a human H-Ras interaction profile that is the same as that seen for Raf1 and yeast adenylyl cyclase, two known effectors of Ras. Moreover, Raf1 directly competes with Rin1 for binding to H-Ras in vitro. Unlike Raf1, however, the Rin1 protein resides primarily at the plasma membrane, where H Ras is localized. These data are consistent with Rin1 functioning in mammalian cells as an effector or regulator of H-Ras. PMID- 7862126 TI - Association of the vav proto-oncogene product with poly(rC)-specific RNA-binding proteins. AB - We have used the yeast two-hybrid system to isolate proteins that interact with the carboxy-terminal SH3-SH2-SH3 region of Vav. One of the clones encoded heterogeneous nuclear ribonucleoprotein K (hnRNP K), a poly(rC)-specific RNA binding protein. The interaction between Vav and hnRNP K involves the binding of the most carboxy-terminal SH3 domain of Vav to two proline-rich sequences present in the central region of hnRNP K. Overexpression of Vav in mouse fibroblasts leads to the formation of a stable complex with the endogenous hnRNP K and to the preferential redistribution of this protein to the cytoplasmic fraction. More importantly, Vav and hnRNP K proteins also interact in hematopoietic cells. In addition, Vav associates in vitro with a second 45-kDa poly(rC)-specific RNA binding protein via its SH3-SH2-SH3 region. These results suggest that Vav plays a role in the regulation of the late steps of RNA biogenesis by modulating the function of poly(rC)-specific ribonucleoproteins. PMID- 7862127 TI - Pentadecamer-binding proteins: definition of two independent protein-binding sites needed for functional activity. AB - The SP6 kappa-promoter pentadecamer (pd) element was found to be unable to stimulate transcription when present in one copy as the only promoter element in a minimal promoter but showed weak stimulatory activity when present as a multimer (four copies). One copy of the pd element acted synergistically with an octamer element, but not with a SP1 site, to stimulate transcription. The effect was orientation dependent with regard to the pd element. Gel shift analysis showed that pd-binding proteins were expressed in transformed as well as nontransformed B lymphocytes, irregardless of their differentiation stage, and in HeLa cells. Two major complexes, binding to different sites within the pd element, were observed in gel shifts. A low-molecular-weight form dominated in resting cells, while a higher-molecular-weight form appeared after mitogenic stimulation. Southwestern analysis showed that the low-molecular-weight pd binding protein had a molecular mass of 35 kDa, which was confirmed by fractionation by denaturating polyacrylamide gel electrophoresis and molecular sieving. The higher-molecular-weight complex was sensitive to detergent treatment, while the low-molecular-weight complex was not. Mutation analysis showed that the two pd-binding complexes interacted with distinct sites within the element and that dual occupancy was required for functional activity. The functional synergy between the pd element and the octamer was more pronounced in plasmacytomas than in B-cell lymphomas. PMID- 7862128 TI - Homotypic interactions of chicken GATA-1 can mediate transcriptional activation. AB - We used a one-hybrid system to replace precisely the finger II chicken GATA-1 DNA binding domain with the binding domain of bacterial repressor protein LexA. The LexA DNA-binding domain lacks amino acids that function for transcriptional activation, nuclear localization, or protein dimerization. This allowed us to analyze activities of GATA-1 sequences distinct from DNA binding. We found that strong transcriptional activating sequences that function independently of finger II are present in GATA-1. Sequences including finger I contain an independent nuclear localizing function. Our data are consistent with cooperative binding of two LexA-GATA-1 hybrid proteins on a palindromic operator. The sensitivity of our transcription assay provides the first evidence that GATA-1 can make homotypic interactions in vivo. The ability of a non-DNA-binding form of GATA-1 to activate gene expression by targeting to a bound GATA-1 derivative further supports the notion that GATA-1-GATA-1 interactions may have functional consequences. A coimmunoprecipitation assay was used to demonstrate that GATA-1 multimeric complexes form in solution by protein-protein interaction. The novel ability of GATA-1 to interact homotypically may be important for the formation of higher order structures among distant regulatory elements that share binding sites for this transcription factor. We also used the system to test the ability of GATA-1 to interact heterotypically with other activators. PMID- 7862129 TI - Decreased expression of hepatocyte nuclear factor 3 alpha during the acute-phase response influences transthyretin gene transcription. AB - Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (alpha, beta, and gamma) are known to regulate the transcription of numerous liver-specific genes. The HNF-3 proteins bind to DNA as monomers through a winged-helix motif, which is also utilized by a number of developmental regulators, including the Drosophila homeotic fork head (fkh) protein. We have previously characterized a strong affinity HNF-3S site in the transthyretin (TTR) promoter region which is essential for expression in human hepatoma (HepG2) cells. In the current study, we identify an activating protein 1 (AP-1) site which partially overlaps the HNF 3S sequence in the TTR promoter. We show that in HepG2 cells the AP-1 sequence confers 12-O-tetradecanoylphorbol-13-acetate inducibility to the TTR promoter and contributes to normal TTR transcriptional activity. We also demonstrate that the HNF-3 proteins and AP-1 bind independently to the TTR AP-1-HNF-3 site, and cotransfection experiments suggest that they do not cooperate to activate an AP-1 HNF-3 reporter construct. In addition, 12-O-tetradecanoylphorbol-13-acetate exposure of HepG2 cells results in a reciprocal decrease in HNF-3 alpha and -3 gamma expression which may facilitate interaction of AP-1 with the TTR AP-1-HNF-3 site. In order to explore the role of HNF-3 in the liver, we have examined expression patterns of TTR and HNF-3 during the acute-phase response and liver regeneration. Partial hepatectomy produced minimal fluctuation in HNF-3 and TTR expression, suggesting that HNF-3 expression is not influenced by proliferative signals induced during liver regeneration. In acute-phase livers, we observed a dramatic reduction in HNF-3 alpha expression which correlates with a decrease in the expression of its target gene, the TTR gene. Furthermore, consistent with previous studies, the acute-phase livers are induced for c-jun but not c-fos expression. We propose that the reduction in TTR gene expression during the acute phase is likely due to lower HNF-3 alpha expression levels and that the induction of primarily c-jun homodimers, which are poor transcriptional activators, is insufficient to maintain normal TTR expression levels. We also discuss the role of reduced HNF-3 alpha expression in mediating decreased transcription of HNF-3 target genes which respond negatively to cytokine signalling. PMID- 7862130 TI - A plant mitochondrial sequence transcribed in transgenic tobacco chloroplasts is not edited. AB - RNA editing occurs in two higher-plant organelles, chloroplasts and mitochondria. Because chloroplasts and mitochondria exhibit some similarity in editing site selection, we investigated whether mitochondrial RNA sequences could be edited in chloroplasts. We produced transgenic tobacco plants that contained chimeric genes in which the second exon of a Petunia hybrida mitochondrial coxII gene was under the control of chloroplast gene regulatory sequences. coxII transcripts accumulated to low or high levels in transgenic chloroplasts containing chimeric genes with the plastid ribosomal protein gene rps16 or the rRNA operon promoter, respectively. Exon 2 of coxII was chosen because it carries seven editing sites and is edited in petunia mitochondria even when located in an abnormal context in an aberrant recombined gene. When editing of the coxII transcripts in transgenic chloroplasts was examined, no RNA editing at any of the usual sites was detected, nor was there any novel editing at any other sites. These results indicate that the RNA editing mechanisms of chloroplasts and mitochondria are not identical but must have at least some organelle-specific components. PMID- 7862131 TI - Mutations in PMR1 suppress oxidative damage in yeast cells lacking superoxide dismutase. AB - Mutants of Saccharomyces cerevisiae lacking a functional SOD1 gene encoding Cu/Zn superoxide dismutase (SOD) are sensitive to atmospheric levels of oxygen and are auxotrophic for lysine and methionine when grown in air. We have previously shown that these defects of SOD-deficient yeast cells can be overcome through mutations in either the BSD1 or BSD2 (bypass SOD defects) gene. In this study, the wild type allele of BSD1 was cloned by functional complementation and was physically mapped to the left arm of chromosome VII. BSD1 is identical to PMR1, encoding a member of the P-type ATPase family that localizes to the Golgi apparatus. PMR1 is thought to function in calcium metabolism, and we provide evidence that PMR1 also participates in the homeostasis of manganese ions. Cells lacking a functional PMR1 gene accumulate elevated levels of intracellular manganese and are also extremely sensitive to manganese ion toxicity. We demonstrate that mutations in PMR1 bypass SOD deficiency through a mechanism that depends on extracellular manganese. Collectively, these findings indicate that oxidative damage in a eukaryotic cell can be prevented through alterations in manganese homeostasis. PMID- 7862132 TI - Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase. AB - Double-stranded RNA (dsRNA)-specific adenosine deaminase converts adenosine to inosine in dsRNA. The protein has been purified from calf thymus, and here we describe the cloning of cDNAs encoding both the human and rat proteins as well as a partial bovine clone. The human and rat clones are very similar at the amino acid level except at their N termini and contain three dsRNA binding motifs, a putative nuclear targeting signal, and a possible deaminase motif. Antibodies raised against the protein encoded by the partial bovine clone specifically recognize the calf thymus dsRNA adenosine deaminase. Furthermore, the antibodies can immunodeplete a calf thymus extract of dsRNA adenosine deaminase activity, and the activity can be restored by addition of pure bovine deaminase. Staining of HeLa cells confirms the nuclear localization of the dsRNA-specific adenosine deaminase. In situ hybridization in rat brain slices indicates a widespread distribution of the enzyme in the brain. PMID- 7862133 TI - c-jun inhibits insulin control element-mediated transcription by affecting the transactivation potential of the E2A gene products. AB - Pancreatic beta-cell-type-specific transcription of the insulin gene is principally controlled by trans-acting factors which influence insulin control element (ICE)-mediated expression. The ICE activator is composed, in part, of the basic helix-loop-helix proteins E12, E47, and E2-5 encoded by the E2A gene. Previous experiments showed that ICE activation in beta cells was repressed in vivo by the c-jun proto-oncogene (E. Henderson and R. Stein, Mol. Cell. Biol. 14:655-662, 1994). Here we focus on the mechanism by which c-Jun inhibits ICE mediated activation. c-Jun was shown to specifically repress the transactivation potential of the E2A proteins. Thus, we found that the activity of GAL4:E2A fusion constructs was inhibited by c-Jun. The transrepression capabilities of c Jun were detected only in pancreatic islet cell lines that contained a functional ICE activator. Repression of GAL4:E2A was mediated by the basic leucine zipper regions of c-Jun, which are also the essential regions of this protein necessary for controlling ICE activator-stimulated expression in vivo. The specific target of c-Jun repression was the transactivation domain (located between amino acids 345 and 408 in E12 and E47) conserved in E12, E47, and E2-5. In contrast, the activation domain unique to the E12 and E47 proteins (located between amino acids 1 and 99) was unresponsive to c-Jun. Our results indicate that c-Jun inhibits insulin gene transcription in beta cells by reducing the transactivation potential of the E2A proteins present in the ICE activator complex. PMID- 7862134 TI - Binding of disparate transcriptional activators to nucleosomal DNA is inherently cooperative. AB - To investigate mechanisms by which multiple transcription factors access complex promoters and enhancers within cellular chromatin, we have analyzed the binding of disparate factors to nucleosome cores. We used a purified in vitro system to analyze binding of four activator proteins, two GAL4 derivatives, USF, and NF kappa B (KBF1), to reconstituted nucleosome cores containing different combinations of binding sites. Here we show that binding of any two or all three of these factors to nucleosomal DNA is inherently cooperative. Thus, the binuclear Zn clusters of GAL4, the helix-loop-helix/basic domains of USF, and the rel domain of NF-kappa B all participated in cooperative nucleosome binding, illustrating that this effect is not restricted to a particular DNA-binding domain. Simultaneous binding by two factors increased the affinity of individual factors for nucleosomal DNA by up to 2 orders of magnitude. Importantly, cooperative binding resulted in efficient nucleosome binding by factors (USF and NF-kappa B) which independently possess little nucleosome-binding ability. The participation of GAL4 derivatives in cooperative nucleosome binding required only DNA-binding and dimerization domains, indicating that disruption of histone-DNA contacts by factor binding was responsible for the increased affinity of additional factors. Cooperative nucleosome binding required sequence-specific binding of all transcription factors, appeared to have spatial constraints, and was independent of the orientation of the binding sites on the nucleosome. These results indicate that cooperative nucleosome binding is a general mechanism that may play a significant role in loading complex enhancer and promoter elements with multiple diverse factors in chromatin and contribute to the generation of threshold responses and transcriptional synergy by multiple activator sites in vivo. PMID- 7862135 TI - Cloning and characterization of a Xenopus poly(A) polymerase. AB - During oocyte maturation and early embryogenesis in Xenopus laevis, the translation of several mRNAs is regulated by cytoplasmic poly(A) elongation, a reaction catalyzed by poly(A) polymerase (PAP). We have cloned, sequenced, and examined several biochemical properties of a Xenopus PAP. This protein is 87% identical to the amino-terminal portion of bovine PAP, which catalyzes the nuclear polyadenylation reaction, but lacks a large region of the corresponding carboxy terminus, which contains the nuclear localization signal. When injected into oocytes, the Xenopus PAP remains concentrated in the cytoplasm, suggesting that it is a specifically cytoplasmic enzyme. Oocytes contain several PAP mRNA related transcripts, and the levels of at least the one encoding the putative cytoplasmic enzyme are relatively constant in oocytes and early embryos but decline after blastulation. When expressed in bacteria and purified by affinity and MonoQ-Sepharose chromatography, the protein has enzymatic activity and adds poly(A) to a model substrate. Importantly, affinity-purified antibodies directed against Xenopus PAP inhibit cytoplasmic polyadenylation in egg extracts. These data suggest that the PAP described here could participate in cytoplasmic polyadenylation during Xenopus oocyte maturation. PMID- 7862136 TI - Activation of phospholipase C gamma in Schizosaccharomyces pombe by coexpression of receptor or nonreceptor tyrosine kinases. AB - The fission yeast Schizosaccharomyces pombe has no detectable endogenous receptor tyrosine kinases or associated signalling apparatus, and we have used this cell system to reconstitute mammalian platelet-derived growth factor beta (PDGF beta) receptor-linked activation of phospholipase C gamma 2 (PLC gamma 2). The PDGF beta receptor migrates as a glycosylated protein of 165 kDa associated exclusively with membrane fractions. No tyrosine autophosphorylation was detected when PDGF beta was expressed alone. PLC gamma 2 appears as a 140-kDa protein distributed between particulate and soluble fractions which exhibits characteristic selectivity for phosphatidylinositol 4,5-bisphosphate and is sensitive to powerful activation by Ca2+. When coexpressed, both PDGF beta and PLC gamma 2 undergo tyrosine phosphorylation, and this is accompanied by a > 26 fold increase in [3H]inositol 4,5-biphosphate ([3H]IP2) and [3H]inositol 1,4,5 triphosphate [3H]IP3 production. Treatment with the tyrosine phosphatase inhibitor pervanadate further increased PLC gamma 2 tyrosine phosphorylation as well as [3H]IP2 and [3H]IP3 generation. Phosphorylated PLC gamma 2 was found predominantly in membrane fractions. To test a nonreceptor tyrosine kinase, we then expressed the human proto-oncogene c-src together with its negative regulator Csk. These were immunodetectable as bands at 60 kDa (c-Src) and 50 kDa (Csk) and distributed between membrane and cytosolic fractions. When yeast coexpressing c-Src, Csk, and PLC gamma 2 was incubated with pervanadate, PLC gamma 2 was tyrosine phosphorylated and [3H]IP2 and [3H]IP3 production increased 11.0- and 7.0-fold, respectively. Csk expressed alone with PLC gamma 2 was ineffective. Similar PLC gamma 2 activation was observed upon in vitro mixing with the extracts expressing either c-Src or the PDGF beta receptor. In summary, this is the first report of a reconstitution of mammalian tyrosine kinase-linked effector activation in yeast cells and also the first demonstration of direct PLC gamma 2 activation by the proto-oncogene c-src. These observations indicate that S. pombe provides a powerful cell system in which to study critical molecular interactions and activities underlying receptor and nonreceptor tyrosine kinase dependent cell signaling. PMID- 7862137 TI - Basal promoter of the rat connexin 32 gene: identification and characterization of an essential element and its DNA-binding protein. AB - The connexin 32 (Cx32) gene, a member of a multigene family, is expressed preferentially in the liver. The basal promoter complex of the rat Cx32 gene was previously localized to a 146-bp region (map positions [mp] -179 to -34) immediately upstream of the first exon. To investigate the biochemical factors contributing to the basal promoter activity, nuclear protein-DNA complexes within this region (mp -177 to -106) were investigated by using a DNA mobility shift assay. Three DNA-protein binding activities, termed Cx32-B1, Cx32-B2, and Cx32 B3, were identified with nuclear protein extracts from hepatoma cell lines, HuH7 and FAO-1. However, only Cx32-B2 binding activity was detected in nuclear protein extract from normal rat liver tissue. This activity was significantly more abundant in rat liver tissue than in hepatoma cell lines and tissues from various other organs. By using methylation interference footprinting, the Cx32-B2 complex was localized to the region between mp -152 and -127 and a DNA probe containing this region bound to a 60-kDa protein in rat liver nuclear extracts. Mutation of two nucleotides in the Cx32-B2 binding site abrogated the formation of the Cx32 B2 protein-DNA complex and significantly reduced the transcriptional activity of the Cx32 promoter. These results indicate that the Cx32-B2 complex is an essential component of the rat Cx32 basal promoter and is likely a major factor in the preferential expression of this gene in the liver. PMID- 7862138 TI - The p53-mediated G1 checkpoint is retained in tumorigenic rat embryo fibroblast clones transformed by the human papillomavirus type 16 E7 gene and EJ-ras. AB - Rat embryo fibroblast clones transformed with the human papillomavirus type 16 E7 gene and the H-ras oncogene (ER clones) fall into two groups on the basis of endogenous p53 genotype, wild type or mutant. We have compared these clones with the aim of indentifying physiological differences that could be attributed to p53 protein function. We show that all ER clones, regardless of p53 gene status, are tumorigenic and metastatic in severe combined immunodeficiency mice. We demonstrate that only the wild-type p53 protein expressed in ER clones is functional on the basis of its site-specific double-stranded DNA-binding activity and its ability to confer a G1 delay on cells following treatment with ionizing radiation. These data indicate that disruption of the p53 growth-regulatory pathway is not a prerequisite for the malignant conversion of rat embryo fibroblasts expressing the E7 gene and mutant ras. Differences in phenotype that were correlated with loss of p53 protein function included the following: serum independent growth of ER clones in culture, decreased tumor doubling time in vivo, and increased radioresistance. In addition, we demonstrate the p53 dependent G1 checkpoint alone does not determine radiosensitivity. PMID- 7862139 TI - TFIIIB placement on a yeast U6 RNA gene in vivo is directed primarily by TFIIIC rather than by sequence-specific DNA contacts. AB - The Saccharomyces cerevisiae U6 RNA gene (SNR6), which is transcribed by RNA polymerase III, has an unusual combination of promoter elements: an upstream TATA box, an intragenic A block, and a downstream B block. In tRNA genes, the A and B blocks are binding sites for the transcription initiation factor TFIIIC, which positions TFIIIB a fixed distance upstream of the A block. However, in vitro transcription of SNR6 with purified components requires neither TFIIIC nor the A and B blocks, presumably because TFIIIB recognizes the upstream sequences directly. Here we demonstrate that TFIIIB placement on SNR6 in vivo is directed primarily by the TFIIIC-binding elements rather than by upstream sequences. We show that the A block is a stronger start site determinant than the upstream sequences when the two are uncoupled by an insertion mutation. Furthermore, while TFIIIC-independent in vitro transcription of SNR6 is highly sensitive to TATA box point mutations, in vivo initiation on SNR6 is only marginally sensitive to such mutations unless the A block is mutated. Intriguingly, a deletion downstream of the U6 RNA coding region that reduces A-to-B block spacing also increases in vivo dependence on the TATA box. Moreover, this deletion results in the appearance of micrococcal nuclease-hypersensitive sites in the TFIIIB chromatin footprint, indicating that TFIIIB binding is disrupted by a mutation 150 bp distant. This and additional chromatin footprinting data suggest that SNR6 is assembled into a nucleoprotein complex that facilitates the TFIIIC-dependent binding of TFIIIB. PMID- 7862140 TI - Termination-altering mutations in the second-largest subunit of yeast RNA polymerase III. AB - In order to identify catalytically important amino acid changes within the second largest subunit of yeast RNA polymerase III, we mutagenized selected regions of its gene (RET1) and devised in vivo assays for both increased and decreased transcription termination by this enzyme. Using as the reporter gene a mutant SUP4-o tRNA gene that in one case terminates prematurely and in the other case fails to terminate, we screened mutagenized RET1 libraries for reduced and increased transcription termination, respectively. The gain in suppression phenotype was in both cases scored as a reduction in the accumulation of red pigment in yeast strains harboring the ade2-1 ochre mutation. Termination altering mutations were obtained in regions of the RET1 gene encoding amino acids 300 to 325, 455 to 486, 487 to 521, and 1061 to 1082 of the protein. In degree of amino acid sequence conservation, these range from highly variable in the first to highly conserved in the last two regions. Residues 300 to 325 yielded mainly reduced-termination mutants, while in region 1061 to 1082, increased-termination mutants were obtained exclusively. All mutants recovered, while causing gain of suppression with one SUP4 allele, brought about a reduction in suppression with the other allele, thus confirming that the phenotype is due to altered termination rather than an elevated level of transcription initiation. In vitro transcription reactions performed with extracts from several strong mutants demonstrated that the mutant polymerases respond to RNA terminator sequences in a manner that matches their in vivo termination phenotypes. PMID- 7862141 TI - The sak1+ gene of Schizosaccharomyces pombe encodes an RFX family DNA-binding protein that positively regulates cyclic AMP-dependent protein kinase-mediated exit from the mitotic cell cycle. AB - In Schizosaccharomyces pombe, meiosis is initiated by conditions of nutrient deprivation. Mutations in genes encoding elements of the cyclic AMP-dependent protein kinase (cAPK) pathway interfere with meiosis. Loss-of-function alleles of genes that stimulate the activity of cAPK allow cells to bypass the normal requirement of starvation for conjugation and meiosis. Alternatively, loss-of function alleles of genes that inhibit cAPK lead to the inability to undergo sexual differentiation. The cgs1+ gene encodes the regulatory subunit of cAPK, and the cgs2+ gene encodes a cyclic AMP phosphodiesterase. Thus, both genes encode proteins which negatively regulate the activity of cAPK. Loss of either cgs1 or cgs2 prevents haploid cells from conjugating and diploid cells from undergoing meiosis. In addition to these defects, cells are unable to enter stationary phase. We describe a novel gene, sak1+, which when present on a plasmid overcomes the aberrant phenotypes associated with unregulated cAPK activity. Genetic analysis of sak1+ (suppressor of A-kinase) reveals that it functions downstream of cyclic AMP-dependent protein kinase to allow cells to exist the mitotic cycle and enter either stationary phase or the pathway leading to sexual differentiation. The sak1+ gene is essential for cell viability, and a null allele causes multiple defects in cell morphology and nuclear division. Thus, sak1+ is an important regulatory element in the life cycle of S. pombe. Sequence analysis shows that the predicted product of the sak1+ gene is an 87-kDa protein which shares homology to the RFX family of DNA-binding proteins identified in humans and mice. One member of this family, RFX1, is a transcription factor for a variety of viral and cellular genes. PMID- 7862142 TI - Sequence and structural requirements for high-affinity DNA binding by the WT1 gene product. AB - The Wilms' tumor suppressor gene, WT1, encodes a zinc finger polypeptide which plays a key role regulating cell growth and differentiation in the urogenital system. Using the whole-genome PCR approach, we searched murine genomic DNA for high-affinity WT1 binding sites and identified a 10-bp motif 5'GCGTGGGAGT3' which we term WTE). The WTE motif is similar to the consensus binding sequence 5'GCG(G/T)GGGCG3' recognized by EGR-1 and is also suggested to function as a binding site for WT1, setting up a competitive regulatory loop. To evaluate the underlying biochemical basis for such competition, we compared the binding affinities of WT1 and EGR1 for both sequences. WT1 shows a 20- to 30-fold-higher affinity for the WTE sequence compared with that of the EGR-1 binding motif. Mutational analysis of the WTE motif revealed a significant contribution to binding affinity by the adenine nucleotide at the eighth position (5'GCGTGGGAGT3') as well as by the 3'-most thymine (5'GCGTGGGAGT3'), whereas mutations in either flanking nucleotides or other nucleotides in the core sequence did not significantly affect the specific binding affinity. Mutations within WT1 zinc fingers II to IV abolished the sequence-specific binding of WT1 to WTE, whereas alterations within the first WT1 zinc finger reduced the binding affinity approximately 10-fold but did not abolish sequence recognition. We have thus identified a WT1 target, which, although similar in sequence to the EGR-1 motif, shows a 20- to 30-fold-higher affinity for WT1. These results suggest that physiological action of WT1 is mediated by binding sites of significantly higher affinity than the 9-bp EGR-1 binding motif. The role of the thymine base in contributing to binding affinity is discussed in the context of recent structural analysis. PMID- 7862143 TI - Genetic dissection of thyroid hormone receptor beta: identification of mutations that separate hormone binding and transcriptional activation. AB - The thyroid hormone receptors (TR) are members of the nuclear receptor family of ligand-mediated transcription factors. The large region of TR that lies C terminal to its DNA-binding domain subserves functions of ligand binding, dimerization, and transactivation. Little is known regarding the structural or functional determinants of these processes. We have utilized genetic screening in the yeast Saccharomyces cerevisiae to identify residues involved in these functions. Random mutations of the rat TR beta 1 isoform between amino acid residues 179 and 456 were screened, and mutants with reduced hormone-dependent activation of reporter gene activity were isolated. In this paper we describe the characterization of a class of mutants that exhibit a dissociation between hormone binding and transcriptional activation. These mutants retained hormone binding (> 15% of the wild-type level) yet failed to transactivate a reporter gene. A number of these mutations occurred within the D region, which links the DNA-binding and ligand-binding domains of the receptor. One subset of these mutations abrogated DNA binding, supporting a role of the D region in this process. The remainder retain DNA binding and thus highlight residues critical for receptor activation. In addition, an unexpected group of "superactivator" mutations that led to enhanced hormone-dependent activation in S. cerevisiae were found. These mutations localized to the carboxy-terminal portion of the receptor in a region which contains elements conserved across the superfamily of nuclear receptors. The hormone-dependent phenotype of these superactivator mutations suggests an important role of this segment in ligand-mediated transcriptional activation. PMID- 7862144 TI - A novel enhancer, the pro-B enhancer, regulates Id1 gene expression in progenitor B cells. AB - The helix-loop-helix (HLH) Id proteins have been reported to function as inhibitors of various differentiation programs. The HLH motif mediates dimer formation between Id and the basic HLH transcription factors. Since Id proteins lack the basic region responsible for DNA binding, the heterodimers cannot bind to DNA. Id proteins have also been found to be involved in early B-cell differentiation. They are expressed at high levels in progenitor B cells (pro-B cells), and the expression is diminished in pre-B cells and mature B cells. This expression pattern correlates inversely with basic HLH protein activity and immunoglobulin enhancer function in B-cell development. Regulation of Id expression may play an important role in transcriptional control of immunoglobulin genes and therefore in B-cell differentiation. We have characterized the regulatory elements of the Id1 gene. Using stable transfectants, transient transfection, and mobility shift assays, we have identified an 8-bp element designated PBE (pro-B enhancer) downstream of the Id1 gene that is responsible for a pro-B-cell-specific enhancer activity. A pro-B cell-specific protein complex was found to bind to the 8-bp PBE element. Substitution mutagenesis at this binding site showed that it is indeed of functional importance in regulating the pro-B-cell-specific expression of the Id1 gene. PMID- 7862145 TI - The PAX3-FKHR fusion protein created by the t(2;13) translocation in alveolar rhabdomyosarcomas is a more potent transcriptional activator than PAX3. AB - Alveolar rhabdomyosarcomas are pediatric solid tumors with a hallmark cytogenetic abnormality: translocation of chromosomes 2 and 13 [t(2;13) (q35;q14)]. The genes on each chromosome involved in this translocation have been identified as the transcription factor-encoding genes PAX3 and FKHR. The NH2-terminal paired box and homeodomain DNA-binding domains of PAX3 are fused in frame to COOH-terminal regions of the chromosome 13-derived FKHR gene, a novel member of the forkhead DNA-binding domain family. To determine the role of the fusion protein in transcriptional regulation and oncogenesis, we identified the PAX3-FKHR fusion protein and characterized its function(s) as a transcription factor relative to wild-type PAX3. Antisera specific to PAX3 and FKHR were developed and used to examine PAX3 and PAX3-FKHR expression in tumor cell lines. Sequential immunoprecipitations with anti-PAX3 and anti-FKHR sera demonstrated expression of a 97-kDa PAX3-FKHR fusion protein in the t(2;13)-positive rhabdomyosarcoma Rh30 cell line and verified that a single polypeptide contains epitopes derived from each protein. The PAX3-FKHR protein was localized to the nucleus in Rh30 cells, as was wild-type PAX3, in t(2;13)-negative A673 cells. In gel shift assays using a canonical PAX binding site (e5 sequence), we found that DNA binding of PAX3 FKHR was significantly impaired relative to that of PAX3 despite the two proteins having identical PAX DNA-binding domains. However, the PAX3-FKHR fusion protein was a much more potent transcriptional activator than PAX3 as determined by transient cotransfection assays using e5-CAT reporter plasmids. The PAX3-FKHR protein may function as an oncogenic transcription factor by enhanced activation of normal PAX3 target genes. PMID- 7862146 TI - An essential domain of the c-myc protein interacts with a nuclear factor that is also required for E1A-mediated transformation. AB - Cell transformation by nuclear oncogenes such as c-myc presumably involves the transcriptional activation of a set of target genes that participate in the control of cell division. The function of a small evolutionarily conserved domain of the c-myc gene encompassing amino acids 129 to 145 was analyzed to explore the relationship between cell transformation and transcriptional activation. Deletion of this domain inactivated the c-myc oncogene for cell transformation while retaining the ability to activate transcription of either myc consensus binding sites or a GAL4-dependent promoter when the c-myc N-terminus was fused to the GAL4 DNA-binding domain. Point mutations that altered a conserved tryptophan (amino acid 136) within this domain had similar effects. Expression of the wt c Myc N terminus (amino acids 1 to 262) as a GAL4 fusion was a dominant inhibitor of cell transformation by the c-myc oncogene, and this same domain also inhibited transformation by the adenovirus E1A gene. Surprisingly, deletion of amino acids 129 to 145 eliminated the dominant negative activity of GAL4-Myc on both c-myc and E1A transformation. Expression of the GAL4-Myc protein in Cos cells led to the formation of a specific complex between the Myc N terminus and a nuclear factor, and this complex was absent with the dl129-145 mutant. These results suggest that an essential domain of the c-Myc protein interacts with a specific nuclear factor that is also required for E1A transformation. PMID- 7862147 TI - Inhibition of HMGI-C protein synthesis suppresses retrovirally induced neoplastic transformation of rat thyroid cells. AB - Elevated expression of the three high-mobility group I (HMGI) proteins (HMGI, HMGY, and HMGI-C) has previously been correlated with the presence of a highly malignant phenotype in epithelial and fibroblastic rat thyroid cells and in experimental thyroid, lung, mammary, and skin carcinomas. Northern (RNA) blot and run-on analyses demonstrated that the induction of HMGI genes in transformed thyroid cells occurs at the transcriptional level. An antisense methodology to block HMGI-C protein synthesis was then used to analyze the role of this protein in the process of thyroid cell transformation. Transfection of an antisense construct for the HMGI-C cDNA into normal thyroid cells, followed by infection with transforming myeloproliferative sarcoma virus or Kirsten murine sarcoma virus, generated cell lines that expressed significant levels of the retroviral transforming oncogenes v-mos or v-ras-Ki and removed the dependency on thyroid stimulating hormones. However, in contrast with untransfected cells or cells transfected with the sense construct, those containing the antisense construct did not demonstrate the appearance of any malignant phenotypic markers (growth in soft agar and tumorigenicity in athymic mice). A great reduction of the HMGI-C protein levels and the absence of the HMGI(Y) proteins was observed in the HMGI-C antisense-transfected, virally infected cells. Therefore, the HMGI-C protein seems to play a key role in the transformation of these thyroid cells. PMID- 7862148 TI - Transcriptional activators differ in their responses to overexpression of TATA box-binding protein. AB - We investigated how overexpression of human TATA-box-binding protein (TBP) affects the action of estrogen receptor (ER) and compared the response with that of other activators. When ER activates a simple promoter, consisting of a response element and either the collagenase or tk TATA box, TBP overexpression potentiates transcription. TBP potentiates only estrogen-induced and not basal transcription and does so independent of spacing between response element and TATA box. TBP overexpression also reduces autoinhibition by overexpressed ER, suggesting that one target of the autoinhibition may be TBP itself. Both AF-1 and AF-2 domains of ER are potentiated by TBP, and each domain binds TBP in vitro. Like ER, chimeric GAL4/VP16 and GAL4/Tat activators are also potentiated by TBP, as is the synergistic activation by ER and GAL4/VP16 on a complex promoter. Unlike ER, GAL4/Sp1 and GAL4/NF-I become less potent when TBP is overexpressed. Furthermore, synergy between ER and Sp1 or between ER and NF-I, whether these are supplied by transfected GAL4 fusions or by the endogenous genes, is inhibited by TBP overexpression. Thus, ER resembles VP16 in response to TBP overexpression and is different from Sp1 and NF-I, which predominate over ER in setting the response on complex promoters. PMID- 7862149 TI - Three different regulatory mechanisms enable yeast hexose transporter (HXT) genes to be induced by different levels of glucose. AB - The HXT genes (HXT1 to HXT4) of the yeast Saccharomyces cerevisiae encode hexose transporters. We found that transcription of these genes is induced 10- to 300 fold by glucose. Analysis of glucose induction of HXT gene expression revealed three types of regulation: (i) induction by glucose independent of sugar concentration (HXT3); (ii) induction by low levels of glucose and repression at high glucose concentrations (HXT2 and HXT4); and (iii) induction only at high glucose concentrations (HXT1). The lack of expression of all four HXT genes in the absence of glucose is due to a repression mechanism that requires Rgt1p and Ssn6p. GRR1 seems to encode a positive regulator of HXT expression, since grr1 mutants are defective in glucose induction of all four HXT genes. Mutations in RGT1 suppress the defect in HXT expression caused by grr1 mutations, leading us to propose that glucose induces HXT expression by activating Grr1p, which inhibits the function of the Rgt1p repressor. HXT1 expression is also induced by high glucose levels through another regulatory mechanism: rgt1 mutants still require high levels of glucose for maximal induction of HXT1 expression. The lack of induction of HXT2 and HXT4 expression on high levels of glucose is due to glucose repression: these genes become induced at high glucose concentrations in glucose repression mutants (hxk2, reg1, ssn6, tup1, or mig1). Components of the glucose repression pathway (Hxk2p and Reg1p) are also required for generation of the high-level glucose induction signal for expression of the HXT1 gene. Thus, the glucose repression and glucose induction mechanisms share some of the same components and may share the same primary signal generated from glucose. PMID- 7862150 TI - Disruption of transforming growth factor beta signaling by a mutation that prevents transphosphorylation within the receptor complex. AB - T beta R-II (transforming growth factor beta [TGF-beta] type II receptor) is a transmembrane serine/threonine kinase that acts as the primary TGF-beta receptor. Ligand binding to T beta R-II leads to the recruitment and phosphorylation of T beta R-I, a distantly related transmembrane kinase that acts as a downstream signaling component. T beta R-I phosphorylation by T beta R-II is shown here to be essential for signaling. A mutant T beta R-II that binds ligand but lacks signaling activity was identified. This mutant was identified by screening with a TGF-beta-inducible vector a series of mink lung epithelial cell clones that have normal TGF-beta binding activity but have lost antiproliferative and transcriptional responses to TGF-beta. When transiently cotransfected with T beta R-II, one of these cell lines, S-21, recovered TGF-beta responsiveness. cDNA cloning and sequencing of T beta R-II from S-21 cells revealed a point mutation that changes proline 525 to leucine in kinase subdomain XI. A recombinant receptor containing this mutation, T beta R-II(P525L), is similar to wild-type T beta R-II in its abilities to bind ligand, support ligand binding to T beta R-I, and form a complex with T beta R-I in vivo. T beta R-II(P525L) has autophosphorylating activity in vitro and in vivo; however, unlike the wild-type receptor, it fails to phosphorylate an associated T beta R-I. These results suggest that T beta R-II(P525L) is a catalytically active receptor that cannot recognize T beta R-I as a substrate. The close link between T beta R-I transphosphorylation and signaling activity argues that transphosphorylation is essential for signal propagation via T beta R-I. PMID- 7862151 TI - The expression pattern of the murine Hoxa-10 gene and the sequence recognition of its homeodomain reveal specific properties of Abdominal B-like genes. AB - Homeobox genes of the Abdominal B (AbdB) family constitute a distinct subset of vertebrate Hox genes. Analysis of the murine Hoxa-10 gene, one member of this family, revealed several properties specific to this class. Two transcripts of Hoxa-10, a10-1 and a10-2, encode homeodomain proteins of 55 kDa (399 amino acids) and 16 kDa (96 amino acids), respectively. These proteins have identical homeodomains and C-terminal regions encoded by a common 3' exon but differ significantly in the sizes of their N-terminal regions because of the usage of alternative 5' exons. The 5' exon of the a10-2 form is also present in transcripts of Hoxa-9, the next 3' gene, indicating that splicing can occur between adjacent AbdB Hox genes within a cluster. Both Hoxa-10 transcripts demonstrated identical patterns of expression in the posterior body and proximal limb bud, differentiating them from AbdB morphogenetic and regulatory transcripts and suggesting a role with other AbdB Hox genes in the patterning of these structures. Finally, a binding site selection identified the sequence AA(A/T)TTTTATTAC as the Hoxa-10 homeodomain consensus binding site, with a TTAT core sequence. Preferential recognition of a TTAT core therefore differentiates the AbdB class from Antennapedia (Antp) class gene products which bind a TAAT core. Thus, in vertebrates, structural similarities, coordinate transcriptional regulation, sites of expression, and binding site preferences all serve to distinguish AbdB from Antp Hox genes. PMID- 7862152 TI - Analysis of protein-DNA and protein-protein interactions of centromere protein B (CENP-B) and properties of the DNA-CENP-B complex in the cell cycle. AB - We previously reported that centromere protein B (CENP-B) forms a stable complex (designated complex A) containing two alphoid DNAs in vitro. Domains in the CENP B polypeptide involved in the formation of complex A were determined in the present study with truncated derivatives expressed in Escherichia coli and in rabbit reticulocyte lysates. It was revealed by gel mobility shift analyses that polypeptides containing the NH2-terminal DNA-binding domain bind a DNA molecule as a monomer, while dimerizing at a novel hydrophobic domain in the COOH-terminal region of 59 amino acid residues. This polypeptide dimerization activity at the COOH-terminal region was also confirmed with the two-hybrid system in Saccharomyces cerevisiae cells. The results thus proved that CENP-B polypeptides form a homodimer at the COOH-terminal hydrophobic domain, each binding a DNA strand at their NH2-terminal domains. The dimerization and DNA-binding domains fall into two of the three completely conserved sequences found in human and mouse CENP-B, and complex A-forming activity was also detected in nuclear extracts of mouse cells. Metaphase-specific phosphorylation of CENP-B was also detected, but this had no effect on its complex A-forming activity. On the basis of the present results, we propose that CENP-B plays an important role in the assembly of specific centromere structures by forming unique DNA-protein complexes at the sites of CENP-B boxes on the centromeric repetitive DNA both in interphase nuclei and on mitotic chromosomes. PMID- 7862153 TI - A novel allele of Saccharomyces cerevisiae RFA1 that is deficient in recombination and repair and suppressible by RAD52. AB - To understand the mechanisms involved in homologous recombination, we have performed a search for Saccharomyces cerevisiae mutants unable to carry out plasmid-to-chromosome gene conversion. For this purpose, we have developed a colony color assay in which recombination is induced by the controlled delivery of double-strand breaks (DSBs). Recombination occurs between a chromosomal mutant ade2 allele and a second plasmid-borne ade2 allele where DSBs are introduced via the site-specific HO endonuclease. Besides isolating a number of new alleles in known rad genes, we identified a novel allele of the RFA1 gene, rfa1-44, which encodes the large subunit of the heterotrimeric yeast single-stranded DNA-binding protein RPA. Characterization of rfa1-44 revealed that it is, like members of the RAD52 epistasis group, sensitive to X rays, high doses of UV, and HO-induced DSBs. In addition, rfa1-44 shows a reduced ability to undergo sporulation and HO induced gene conversion. The mutation was mapped to a single-base substitution resulting in an aspartate at amino acid residue 77 instead of glycine. Moreover, all radiation sensitivities and repair defects of rfa1-44 are suppressed by RAD52 in a dose-dependent manner, and one RAD52 mutant allele, rad52-34, displays nonallelic noncomplementation when crossed with rfa1-44. Presented is a model accounting for this genetic interaction in which Rfa1, in a complex with Rad52, serves to assemble other proteins of the recombination-repair machinery at the site of DSBs and other kinds of DNA damage. We believe that our findings and those of J. Smith and R. Rothstein (Mol. Cell. Biol. 15:1632-1641, 1995) are the first in vivo demonstrations of the involvement of a eukaryotic single-stranded binding protein in recombination and repair processes. PMID- 7862154 TI - A mutation in the gene encoding the Saccharomyces cerevisiae single-stranded DNA binding protein Rfa1 stimulates a RAD52-independent pathway for direct-repeat recombination. AB - In the yeast Saccharomyces cerevisiae, recombination between direct repeats is synergistically reduced in rad1 rad52 double mutants, suggesting that the two genes define alternate recombination pathways. Using a classical genetic approach, we searched for suppressors of the recombination defect in the double mutant. One mutation that restores wild-type levels of recombination was isolated. Cloning by complementation and subsequent physical and genetic analysis revealed that it maps to RAF1. This locus encodes the large subunit of the single stranded DNA-binding protein complex, RP-A, which is conserved from S. cerevisiae to humans. The rfa1 mutation on its own causes a 15-fold increase in direct repeat recombination. However, unlike most other hyperrecombination mutations, the elevated levels in rfa1 mutants occur independently of RAD52 function. Additionally, rfa1 mutant strains grow slowly, are UV sensitive, and exhibit decreased levels of heteroallelic recombination. DNA sequence analysis of rfa1 revealed a missense mutation that alters a conserved residue of the protein (aspartic acid 228 to tyrosine [D228Y]). Biochemical analysis suggests that this defect results in decreased levels of RP-A in mutant strains. Overexpression of the mutant subunit completely suppresses the UV sensitivity and partially suppresses the recombination phenotype. We propose that the defective complex fails to interact properly with components of the repair, replication, and recombination machinery. Further, this may permit the bypass of the recombination defect of rad1 rad52 mutants by activating an alternative single-stranded DNA degradation pathway. PMID- 7862155 TI - BC1 RNA: transcriptional analysis of a neural cell-specific RNA polymerase III transcript. AB - Rodent BC1 RNA represents the first example of a neural cell-specific RNA polymerase III (Pol III) transcription product. By developing a rat brain in vitro system capable of supporting Pol III-directed transcription, we showed that the rat BC1 RNA intragenic promoter elements, comprising an A box element and a variant B box element, as well as its upstream region, containing octamer-binding consensus sequences and functional TATA and proximal sequence element sites, are necessary for transcription. The BC1 B box, lacking the invariant A residue found in the consensus B boxes of tRNAs, represents a functionally related and possibly distinct promoter element. The transcriptional activity of the BC1 B box element is greatly increased, in both a BC1 RNA and a chimeric tRNA(Leu) gene construct, when the BC1 5' flanking region is present and is appropriately spaced. Moreover, a tRNA consensus B-box sequence can efficiently replace the BC1 B box only if the BC1 upstream region is removed. These interactions, identified only in a homologous in vitro system, between upstream Pol II and intragenic Pol III promoters suggest a mechanism by which the tissue-specific BC1 RNA gene and possibly other Pol III-transcribed genes can be regulated. PMID- 7862156 TI - Subcellular localization of the alpha and beta subunits of the acute myeloid leukemia-linked transcription factor PEBP2/CBF. AB - Each of the two human genes encoding the alpha and beta subunits of a heterodimeric transcription factor, PEBP2, has been found at the breakpoints of two characteristic chromosome translocations associated with acute myeloid leukemia, suggesting that they are candidate proto-oncogenes. Polyclonal antibodies against the alpha and beta subunits of PEBP2 were raised in rabbits and hamsters. Immunofluorescence labeling of NIH 3T3 cells transfected with PEBP2 alpha and -beta cDNAs revealed that the full-size alpha A1 and alpha B1 proteins, the products of two related but distinct genes, are located in the nucleus, while the beta subunit is localized to the cytoplasm. Deletion analysis demonstrated that there are two regions in alpha A1 responsible for nuclear accumulation of the protein: one mapped in the region between amino acids 221 and 513, and the other mapped in the Runt domain (amino acids 94 to 221) harboring the DNA-binding and the heterodimerizing activities. When the full-size alpha A1 and beta proteins are coexpressed in a single cell, the former is present in the nucleus and the latter still remains in the cytoplasm. However, the N- or C-terminally truncated alpha A1 proteins devoid of the region upstream or downstream of the Runt domain colocalized with the beta protein in the nucleus. In these cases, the beta protein appeared to be translocated into the nucleus passively by binding to alpha A1. The chimeric protein containing the beta protein at the N-terminal region generated as a result of the inversion of chromosome 16 colocalized with alpha A1 to the nucleus more readily than the normal beta protein. The implications of these results in relation to leukemogenesis are discussed. PMID- 7862157 TI - Expression of the Runt domain-encoding PEBP2 alpha genes in T cells during thymic development. AB - The PEBP2 alpha A and PEBP2 alpha B genes encode the DNA-binding subunit of a murine transcription factor, PEBP2, which is implicated as a T-cell-specific transcriptional regulator. These two related genes share the evolutionarily conserved region encoding the Runt domain. PEBP2 alpha B is the murine counterpart of human AML1, which is located at the breakpoints of the 8;21 and 3;21 chromosome translocations associated with acute myeloid leukemia. Northern (RNA) blots of various adult mouse tissues revealed that the levels of expression of both genes were most prominent in the thymus. Furthermore, transcripts of PEBP2 alpha A and mouse AML1/PEBP2 alpha B were detected in T lymphocytes in the thymuses from day 16 embryos and newborns, as well as 4-week-old adult mice, by in situ hybridization. The expression of the genes persisted in peripheral lymph nodes of adult mice. The transcripts were detected in all the CD4- CD8-, CD4+ CD8+, CD4+ CD8-, and CD4- CD8+ cell populations. The results indicated that both genes are expressed in T cells throughout their development, supporting the notion that PEBP2 is a T-cell-specific transcription factor. Transcripts of mouse AML1/PEBP2 alpha B were also detected in day 12 fetal hematopoietic liver and in the bone marrow cells of newborn mice. The implication of mouse AML1/PEBP2 alpha B expression in hematopoietic cells other than those of T-cell lineage is discussed in relation to myeloid leukemogenesis. PMID- 7862158 TI - The Saccharomyces cerevisiae MVP1 gene interacts with VPS1 and is required for vacuolar protein sorting. AB - The VPS1 gene of Saccharomyces cerevisiae encodes an 80-kDa GTPase that associates with Golgi membranes and is required for the sorting of proteins to the yeast vacuole. Vps1p is a member of a growing family of high-molecular-weight GTPases that are found in a number of organisms and are involved in a variety of cellular processes. Vps1p is most similar to mammalian dynamin and the Drosophila Shibire protein, both of which have been shown to play a role in an early step of endocytosis. To identify proteins that interact with Vps1p, a genetic screen was designed to isolate multicopy suppressors of dominant-negative vps1 mutations. One such suppressor, MVP1, that exhibits genetic interaction with VPS1 and is itself required for vacuolar protein sorting has been isolated. Overproduction of Mvp1p will suppress several dominant alleles of VPS1, and suppression is dependent on the presence of wild-type Vps1p. MVP1 encodes a 59-kDa hydrophilic protein, Mvp1p, which appears to colocalize with Vps1p in vps1d and vps27 delta yeast cells. We therefore propose that Mvp1p and Vps1p act in concert to promote membrane traffic to the vacuole. PMID- 7862159 TI - Meiosis-specific double-strand DNA breaks at the HIS4 recombination hot spot in the yeast Saccharomyces cerevisiae: control in cis and trans. AB - The region of Saccharomyces cerevisiae chromosome III located between the 5' end of the HIS4 gene and the 3' end of the adjacent BIK1 gene has a very high level of meiotic recombination. In wild-type strains, a meiosis-specific double-strand DNA break occurs in the hot spot region. This break is absent in strains in which the transcription factors Rap1p, Bas1p, and Bas2p cannot bind to the region upstream of HIS4. In strains with levels of recombination that are higher than those of the wild type, the break is found at elevated levels. The linear relationship between hot spot activity and the frequency of double-strand DNA breaks suggests that these lesions are responsible for initiating recombination at the HIS4 recombination hot spot. PMID- 7862160 TI - REF2 encodes an RNA-binding protein directly involved in yeast mRNA 3'-end formation. AB - The Saccharomyces cerevisiae mutant ref2-1 (REF = RNA end formation) was originally identified by a genetic strategy predicted to detect decreases in the use of a CYC1 poly(A) site interposed within the intron of an ACT1-HIS4 fusion reporter gene. Direct RNA analysis now proves this effect and also demonstrates the trans action of the REF2 gene product on cryptic poly(A) sites located within the coding region of a plasmid-borne ACT1-lacZ gene. Despite impaired growth of ref2 strains, possibly because of a general defect in the efficiency of mRNA 3' end processing, the steady-state characteristics of a variety of normal cellular mRNAs remain unaffected. Sequencing of the complementing gene predicts the Ref2p product to be a novel, basic protein of 429 amino acids (M(r), 48,000) with a high-level lysine/serine content and some unusual features. Analysis in vitro, with a number of defined RNA substrates, confirms that efficient use of weak poly(A) sites requires Ref2p: endonucleolytic cleavage is carried out accurately but at significantly lower rates in extracts prepared from delta ref2 cells. The addition of purified, epitope-tagged Ref2p (Ref2pF) reestablishes wild-type levels of activity in these extracts, demonstrating direct involvement of this protein in the cleavage step of 3' mRNA processing. Together with the RNA-binding characteristics of Ref2pF in vitro, our results support an important contributing role for the REF2 locus in 3'-end processing. As the first gene genetically identified to participate in mRNA 3'-end maturation prior to the final polyadenylation step, REF2 provides an ideal starting point for identifying related genes in this event. PMID- 7862161 TI - HPR1 encodes a global positive regulator of transcription in Saccharomyces cerevisiae. AB - The Hpr1 protein has an unknown function, although it contains a region of homology to DNA topoisomerase I. We have found that hpr1 null mutants are defective in the transcription of many physiologically unrelated genes, including GAL1, HO, ADH1, and SUC2, by using a combination of Northern (RNA) blot analysis, primer extension, and upstream activation sequence-lacZ fusions. Many of the genes positively regulated by HPR1 also require SWI1, SWI2-SNF2, SWI3, SNF5, and SNF6. The transcriptional defect at HO and the CCB::lacZ upstream activation sequence in hpr1 mutants is partially suppressed by a deletion of SIN1, which encodes an HMG1p-like protein. Elevated gene dosage of either histones H3 and H4 or H2A and H2B results in a severe growth defect in combination with an hpr1 null mutation. However, increased gene dosage of all four histones simultaneously restores near-normal growth in hpr1 mutants. Altered in vivo Dam methylase sensitivity is observed at two HPR1-dependent promoters (GAL1 and SUC2). Most of the Hpr1 protein present in the cell is in a large complex (10(6) Da) that is distinct from the SWI-SNF protein complex. We propose that HPR1 affects transcription and recombination by altering chromatin structure. PMID- 7862162 TI - Autoregulated expression of the yeast INO2 and INO4 helix-loop-helix activator genes effects cooperative regulation on their target genes. AB - In the yeast Saccharomyces cerevisiae, the phospholipid biosynthetic genes are highly regulated at the transcriptional level in response to the phospholipid precursors inositol and choline. In the absence of inositol and choline (derepressing), the products of the INO2 and INO4 genes form a heteromeric complex which binds to a 10-bp element, upstream activation sequence INO (UASINO), in the promoters of the phospholipid biosynthetic genes to activate their transcription. In the presence of inositol and choline (repressing), the product of the OPI1 gene represses transcription dictated by the UASINO element. Curiously, we identified a UASINO-like element in the promoters of both the INO2 and INO4 genes. The presence of the UASINO element in these two promoters suggested that the mechanism for the inositol-choline response would involved regulating expression of the two activator genes. Using a cat reporter gene, we find that INO2-cat expression was regulated 12-fold in response to inositol and choline but that INO4-cat was constitutively expressed. We further observed that INO2-cat was not expressed in either an ino2 or an ino4 mutant strain and was constitutively overexpressed in an opi1 mutant strain. Expression of the INO4-cat gene was affected only by mutation in the INO4 gene itself. Therefore, INO2-cat transcription is regulated by the products of both the INO2 and INO4 genes whereas INO4 must interact with another protein to activate its own transcription. Our data show that derepression of phospholipid biosynthetic gene expression involves two mechanisms: increasing the levels of the INO2 and INO4 gene products and inactivating the OPI1-mediated repression mechanism. We propose a model suggesting that this dual mechanism of regulation accounts for the observed cooperative stimulation of IN01 and CH01 gene expression (phospholipids biosynthetic genes). PMID- 7862163 TI - The mouse DNA polymerase alpha-primase subunit p48 mediates species-specific replication of polyomavirus DNA in vitro. AB - Mouse cell extracts support vigorous replication of polyomavirus (Py) DNA in vitro, while human cell extracts do not. However, the addition of purified mouse DNA polymerase alpha-primase to human cell extracts renders them permissive for Py DNA replication, suggesting that mouse polymerase alpha-primase determines the species specificity of Py DNA replication. We set out to identify the subunit of mouse polymerase alpha-primase that mediates this species specificity. To this end, we cloned and expressed cDNAs encoding all four subunits of mouse and human polymerase alpha-primase. Purified recombinant mouse polymerase alpha-primase and a hybrid DNA polymerase alpha-primase complex composed of human subunits p180 and p68 and mouse subunits p58 and p48 supported Py DNA replication in human cell extracts depleted of polymerase alpha-primase, suggesting that the primase heterodimer or one of its subunits controls host specificity. To determine whether both mouse primase subunits were required, recombinant hybrid polymerase alpha-primases containing only one mouse primase subunit, p48 or p58, together with three human subunits, were assayed for Py replication activity. Only the hybrid containing mouse p48 efficiently replicated Py DNA in depleted human cell extracts. Moreover, in a purified initiation assay containing Py T antigen, replication protein A (RP-A) and topoisomerase I, only the hybrid polymerase alpha-primase containing the mouse p48 subunit initiated primer synthesis on Py origin DNA. Together, these results indicate that the p48 subunit is primarily responsible for the species specificity of Py DNA replication in vitro. Specific physical association of Py T antigen with purified recombinant DNA polymerase alpha-primase, mouse DNA primase heterodimer, and mouse p48 suggested that direct interactions between Py T antigen and primase could play a role in species specific initiation of Py replication. PMID- 7862164 TI - Growth and developmental functions of a human immunodeficiency virus Tat-binding protein/26S protease subunit homolog from Dictyostelium discoideum. AB - We have characterized a newly identified gene from Dictyostelium discoideum, DdTBP alpha, that encodes a member of the family of eukaryotic proteins. These proteins contain a conserved ATPase domain, include subunits of the 26S protease subunit, and are homologous to the mammalian human immunodeficiency virus Tat binding protein TBP1. While information indicates that some family members are involved in the regulation of transcription in mammalian and yeast cells during growth, these proteins are also involved in other cellular functions, and nothing is known about their possible function in multicellular development. The Dictyostelium DdTBP alpha gene is developmentally regulated, with its expression at the highest levels occurring during growth and early development. The gene is present in two copies in the genome. Disruption of one copy by homologous recombination leads to aberrant morphogenesis, which lasts from the formation of the first finger until the onset of culmination. The gene appears to be essential for growth since we were unable to obtain a complete null phenotype and since expression of an inducible antisense construct in the partial null background resulted in cell death. Expression of the antisense construct during development accentuated the partial null phenotype and also resulted in very abnormal fruiting bodies. Overexpression of DdTBP alpha from its own promoter leads to very large multinucleated vegetative cells when the cells are grown in suspension culture. When the cells are plated onto petri dishes in growth medium, they rapidly split into multiple cells containing one to two nuclei, in a manner similar to that of wild-type cells. Overexpressing cells are significantly delayed in forming a multicellular aggregate, but development proceeds normally once the first finger stage is reached. The results indicate that DdTBP alpha plays an important role in regulating both growth and morphogenesis in D. discoideum. PMID- 7862165 TI - Targeted mutagenesis in mammalian cells mediated by intracellular triple helix formation. AB - As an alternative to standard gene transfer techniques for genetic manipulation, we have investigated the use of triple helix-forming oligonucleotides to target mutations to selected genes within mammalian cells. By treating monkey COS cells with oligonucleotides linked to psoralen, we have generated targeted mutations in a simian virus 40 (SV40) vector contained within the cells via intracellular triple helix formation. Oligonucleotide entry into the cells and sequence specific triplex formation within the SV40 DNA deliver the psoralen to the targeted site. Photoactivation of the psoralen by long-wavelength UV light yields adducts and thereby mutations at that site. We engineered into the SV40 vector novel supF mutation reporter genes containing modified polypurine sites amenable to triplex formation. By comparing the abilities of a series of oligonucleotides to target these new sites, we show that targeted mutagenesis in vivo depends on the strength and specificity of the third-strand binding. Oligonucleotides with weak target site binding affinity or with only partial target site homology were ineffective at inducing mutations in the SV40 vectors within the COS cells. We also show that the targeted mutagenesis is dependent on the oligonucleotide concentration and is influenced by the timing of the oligonucleotide treatment and of the UV irradiation of the cells. Frequencies of intracellular targeted mutagenesis in the range of 1 to 2% were observed, depending upon the conditions of the experiment. DNA sequence analysis revealed that most of the mutations were T.A-to-A.T transversions precisely at the targeted psoralen intercalation site. Several deletions encompassing that site were also seen. The ability to target mutations to selected sites within mammalian cells by using modified triplex forming oligonucleotides may provide a new research tool and may eventually lead to therapeutic applications. PMID- 7862166 TI - Detection and characterization of a 3' untranslated region ribonucleoprotein complex associated with human alpha-globin mRNA stability. AB - The highly stable nature of globin mRNA is of central importance to erythroid cell differentiation. We have previously identified cytidine-rich (C-rich) segments in the human alpha-globin mRNA 3' untranslated region (alpha-3'UTR) which are critical in the maintenance of mRNA stability in transfected erythroid cells. In the present studies, we have detected trans-acting factors which interact with these cis elements to mediate this stabilizing function. A sequence specific ribonucleoprotein (RNP) complex is assembled after incubation of the alpha-3'UTR with a variety of cytosolic extracts. This so-called alpha-complex is sequence specific and is not formed on the 3'UTR of either beta-globin or growth hormone mRNAs. Furthermore, base substitutions within the C-rich stretches which destabilize alpha-globin mRNA in vivo result in a parallel disruption of the alpha-complex in vitro. Competition studies with a series of homoribopolymers reveals a striking sensitivity of alpha-complex formation to poly(C), suggesting the presence of a poly(C)-binding activity within the alpha-complex. Three predominant proteins are isolated by alpha-3'UTR affinity chromatography. One of these binds directly to poly(C). This cytosolic poly(C)-binding protein is distinct from previously described nuclear poly(C)-binding heterogeneous nuclear RNPs and is necessary but not sufficient for alpha-complex formation. These data suggest that a messenger RNP complex formed by interaction of defined segments within the alpha-3'UTR with a limited number of cytosolic proteins, including a potentially novel poly(C)-binding protein, is of functional importance in establishing high-level stability of alpha-globin mRNA. PMID- 7862167 TI - Association between GRB2/Sos and insulin receptor substrate 1 is not sufficient for activation of extracellular signal-regulated kinases by interleukin-4: implications for Ras activation by insulin. AB - Insulin receptor substrate 1 (IRS-1) mediates the activation of a variety of signaling pathways by the insulin and insulin-like growth factor 1 receptors by serving as a docking protein for signaling molecules with SH2 domains. We and others have shown that in response to insulin stimulation IRS-1 binds GRB2/Sos and have proposed that this interaction is important in mediating Ras activation by the insulin receptor. Recently, it has been shown that the interleukin (IL)-4 receptor also phosphorylates IRS-1 and an IRS-1-related molecule, 4PS. Unlike insulin, however, IL-4 fails to activate Ras, extracellular signal-regulated kinases (ERKs), or mitogen-activated protein kinases. We have reconstituted the IL-4 receptor into an insulin-responsive L6 myoblast cell line and have shown that IRS-1 is tyrosine phosphorylated to similar degrees in response to insulin and IL-4 stimulation in this cell line. In agreement with previous findings, IL-4 failed to activate the ERKs in this cell line or to stimulate DNA synthesis, whereas the same responses were activated by insulin. Surprisingly, IL-4's failure to activate ERKs was not due to a failure to stimulate the association of tyrosine-phosphorylated IRS-1 with GRB2/Sos; the amounts of GRB2/Sos associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. Moreover, the amounts of phosphatidylinositol 3-kinase activity associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. In contrast to insulin, however, IL-4 failed to induce tyrosine phosphorylation of Shc or association of Shc with GRB2. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Previous studies have indicated that activation of ERks in this cell line is dependent upon Ras since a dominant-negative Ras (Asn-17) blocks ERK activation by insulin. Our findings, taken in the context of previous work, suggest that binding of GRB2/Sos to Shc may be the predominant mechanism whereby insulin as well as cytokine receptors activate Ras. PMID- 7862168 TI - Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins. AB - The interleukin 2 receptor alpha-chain (IL-2R alpha) gene is rapidly and potently induced in T cells in response to mitogenic stimuli. Previously, an inducible enhancer between nucleotides -299 and -228 that contains NF-kappa B and CArG motifs was identified. We now report the characterization of a second essential positive regulatory element located between nucleotides -137 and -64 that binds Elf-1 and HMG-I(Y). This element had maximal activity in lymphoid cells, paralleling the cell type specificity of Elf-1 expression. Transcription from the IL-2R alpha promoter was inhibited when either the Elf-1 or the HMG-I(Y) binding site was mutated. Coexpression of both proteins activated transcription of the 137 to -64 element in COS-7 cells. Elf-1 physically associated with HMG-I and with NF-kappa B p50 and c-Rel in vitro, suggesting that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements. This is the first report of a physical interaction between an Ets family member and NF-kappa B family proteins. These findings provide significant new insights into the protein-protein and protein DNA interactions that regulate cell-type-specific and inducible IL-2R alpha gene expression and also have implications for other genes regulated by Elf-1 and NF kappa B family proteins. PMID- 7862169 TI - Functional analysis of the promoter of the phase-specific WH11 gene of Candida albicans. AB - Candida albicans WO-1 switches spontaneously, frequently, and reversibly between a hemispherical white and a flat gray (opaque) colony-forming phenotype. This transition affects a number of morphological and physiological parameters and involves the activation and deactivation of phase-specific genes. The WH11 gene is transcribed in the white but not the opaque phase. A chimeric WH11-firefly luciferase gene containing the 5' upstream region of WH11 was demonstrated to be under phase regulation regardless of the site of integration, and a series of promoter deletion constructs was used to delineate two white-phase-specific transcription activation domains. Gel retardation experiments with the individual distal or proximal domain and white-phase or opaque-phase protein extract demonstrated the formation of one distal white-phase-specific complex and two proximal white-phase-specific complexes. Specific subfragments were tested for their ability to compete with the entire domain in the formation of complexes with white-phase protein extract in order to map the proximal domain sequence involved in white-phase-specific complex formation. Our results indicate that white-phase-specific transcription of WH11 is positively regulated by trans acting factors interacting with two cis-acting activation sequences in the WH11 promoter. PMID- 7862170 TI - v-rel Induces ectopic expression of an adhesion molecule, DM-GRASP, during B lymphoma development. AB - In an effort to identify aberrantly expressed genes in v-rel-induced tumors, monoclonal antibodies were developed that reacted selectively with avian B-cell tumors. One antibody, HY78, immunoprecipitated a 120-kDa glycoprotein (p120) from cells that express v-rel. N-terminal amino acid sequencing of p120 identified a 27-amino-acid sequence that is also present in DM-GRASP, an adhesion molecule belonging to the immunoglobulin superfamily. Evidence from tissue distribution, immunological cross-reaction, PCR amplification, cDNA cloning, and DNA sequence shows that p120 is indeed DM-GRASP. Northern (RNA) analysis using a probe from the DM-GRASP gene identified a 5.3-kb transcript in mRNA from bursa, thymus, and brain as well as from v-rel-induced B-cell lymphomas but not from bursal B cells. The induction of this protein by v-rel during the development of bursal B-cell lymphomas appears, therefore, to be ectopic in nature. Overexpression of v-rel or c-rel in chicken embryonic fibroblasts, B-cell lines, and spleen mononuclear cells induces the expression of DM-GRASP. The ratio of DM-GRASP to v-Rel was fivefold higher than that of DM-GRASP/c-Rel in a B-cell line, DT95. Interestingly, the presence of HY78 antibody inhibits the in vitro proliferation of v-rel-transformed cells but not cells that immortalized by myc. These data suggest that DM-GRASP is one of the genes induced during v-rel-mediated tumor development and that DM-GRASP may be involved in the growth of v-rel tumor cells. PMID- 7862171 TI - The ligand-binding domains of the thyroid hormone/retinoid receptor gene subfamily function in vivo to mediate heterodimerization, gene silencing, and transactivation. AB - The ligand-binding domains (LBDs) of the thyroid/retinoid receptor gene subfamily contain a series of heptad motifs important for dimeric interactions. This subfamily includes thyroid hormone receptors (T3Rs), all-trans retinoic acid (RA) receptors (RARs), 9-cis RA receptors (RARs and retinoid X receptors [RXRs]), the 1,25-dihydroxyvitamin D3 receptor (VDR), and the receptors that modulate the peroxisomal beta-oxidation pathway (PPARs). These receptors bind to their DNA response elements in vitro as heterodimers with the RXRs. Unliganded receptors in vivo, in particular the T3Rs, can mediate gene silencing and ligand converts these receptors into a transcriptionally active form. The in vivo interactions of these receptors with RXR were studied by using a GAL4-RXR chimera containing the yeast GAL4 DNA-binding domain and the LBD of RXR beta. GAL4-RXR activates transcription from GAL4 response elements in the presence of 9-cis RA. Unliganded T3R, which does not bind or activate GAL4 elements, represses the activation of GAL4-RXR by 9-cis RA in HeLa cells. However, addition of T3 alone leads to transcriptional activation. These findings suggest that T3R can repress or activate transcription while tethered to the LBD of GAL4-RXR and that heterodimerization can occur in vivo without stabilization by hormone response elements. Similar ligand-dependent activation was observed in HeLa cells expressing RAR, VDR, or PPAR and in GH4C1 cells from endogenous receptors. Replacement of the last 17 amino acids of the LBD of RXRbeta with the 90-amino acid transactivating domain of the herpes simplex virus VP16 protein leads to a GAL4 constitutive activator that is repressed by wild-type T3R but not by a ninth heptad mutant that does not form heterodimers. This finding suggests that the ninth heptad or T3R is important for gene silencing and that the LBD of RXR does not exhibit silencing activity. This conclusion was verified with GAL4-LBD chimeras and with wild-type receptors in assays using appropriate response elements. These studies indicate that the LBD has diverse functional roles in gene regulation. PMID- 7862172 TI - A refractory phase in cyclic AMP-responsive transcription requires down regulation of protein kinase A. AB - Cyclic AMP (cAMP) stimulates the expression of numerous genes through the protein kinase A (PK-A)-mediated phosphorylation of the nuclear factor CREB at Ser-133 (G. A. Gonzalez and M. R. Montminy, Cell 59:675-680, 1989). Like other signal transduction pathways, cAMP induces gene expression with burst-attenuation kinetics; cAMP-dependent transcription and CREB phosphorylation peak within 30 min and decline steadily over the next 4 to 6 h via the protein phosphatase 1 mediated dephosphorylation of CREB (M. Hagiwara, A. Alberts, P. Brindle, J. Meinkoth, J. Feramisco, T. Deng, M. Karin, S. Shenolikar, and M. Montminy, Cell 70:105-113, 1992). Here we characterize a third phase in cAMP-responsive transcription--a refractory period during which hormone-treated cells become transcriptionally unresponsive to subsequent stimulation by cAMP. This refractory period begins 6 to 8 h after stimulation and lasts 3 to 5 days after the removal of hormone. In contrast to the earlier attenuation phase, transcription of cAMP responsive genes during the refractory period is not restored by inhibitors of protein phosphatase 1 activity. Rather, the establishment and maintenance of this phase rely on a marked reduction in PK-A catalytic subunit expression at the translational level. As overexpression of C-subunit protein can reactive transcription of cAMP-responsive genes during the refractory period, our results suggest that hormone-responsive cells may stimulate, attenuate, and then silence signal-dependent genes through distinct regulatory mechanisms. PMID- 7862173 TI - Microphthalmia-associated transcription factor as a regulator for melanocyte specific transcription of the human tyrosinase gene. PMID- 7862174 TI - Low levels of reactive oxygen species as modulators of cell function. AB - In this paper, we present various arguments supporting the hypothesis that reactive oxygen species (ROS) could be responsible for the modulation of various cellular functions, besides their well known toxic effects. We first review the recent evidence indicating that ROS are able to modulate genome expression through specific and precise mechanisms during cell activation. The role of the nitrogen reactive radicals such as nitric oxide is separately analyzed because of its specific role in the nervous and vascular systems. The action of the other ROS on gene activation will then be reviewed by first looking at their possible involvement in the activation of transcription factors like NF-kappa B. Arguments will then be developed in favor of the implication of the ROS in the cellular effects of PMA, TNF-alpha and other cytokines on the modulation of the genetic expression. Possible mechanisms will be presented for linking the production of the ROS with cell activation. In a general way we postulate that ROS can play a role of secondary messengers in several cell responses to external stimuli. In the second part of the paper, we will examine the long term influence of ROS and their possible roles in cellular aging. Different links exist between ROS and aging and the relationship between them is probably indirect. We propose to consider the effect of ROS as one of the multiple challenges that cells have to face, the cell being considered as a global system which must optimize its energy expenditure for carrying out its basic functions such as turnover, differentiated phenotype functions, multiplication, defense and repair processes. This thermodynamic point of view will help to understand the effect of low ROS stresses, among others, on accelerated aging. PMID- 7862175 TI - Restriction, methylation and ligation of 5-hydroxymethyluracil-containing DNA. AB - Oxidation of DNA and its components can cause genetic mutations and chromosomal instability. These changes have generally been implicated in aging. Oxidation of the methyl group of thymidine residues in DNA is known to result in the formation 5-hydroxymethyl-2'-deoxyuridine (5HmdUrd). We have utilized Bacillus subtilis phage SPO1 DNA as a model of oxidatively damaged DNA. In this phage, all thymine (Thy) residues are replaced by 5-hydroxymethyluracil (5HmUra), but the species is naturally devoid of other oxidatively-induced DNA lesions. Particular attention was paid to the behavior of 5HmUra-containing DNA as a target for several enzymes employing DNA as substrate; restriction endonucleases, dam DNA methylase and T4 DNA ligase. We noticed that susceptibility of SPO1 DNA varied when different restriction endonucleases having 5HmUra in the restriction sites were tested. Endonucleolytic cleavage brought about Sau3A proceeded as effectively with SPO1 DNA as with conventional DNA (lambda phage). The same was true when the ligation of Sau3A sites was performed with T4 DNA ligase. In contrast, both endonucleolytic cleavage and ligation were slower in SPO1 DNA, compared with lambda phage, when Taq I and T4 DNA ligase were used for restriction and ligation, respectively. We also noticed that SPO1 phage does not naturally contain N6-methyladenine (N6MeAde) opposite 5HmUra, i.e., no hydrolysis of SPO1 DNA was observed when assessed with methylation-dependent restriction endonuclease DpnI. Our results show that the presence of 5HmUra in the respective site of DNA does not, per se, prevent the activity of restriction endonucleases, ligases or DNA methylases. These data support the view that oxidation of Thy to 5HmUra in target DNA does not necessarily result in substantial deterioration in the functions of DNA processing enzymes. PMID- 7862176 TI - Reduction of unscheduled DNA synthesis and plasminogen activator activity in Hutchinson-Gilford fibroblasts during passaging in vitro: partial correction by interferon-beta. AB - Two fibroblast cell lines (PG3KT and PG1NA) derived from Hutchinson-Gilford syndrome (progeria) cases were characterized, at various population doubling levels (PDL), with respect to the capacity of ultraviolet light (UV, mainly 254 nm wavelength)-induced unscheduled DNA synthesis (UDS) and plasminogen activator like protease activity (PA). The UDS levels in PG3KT and PG1NA cells at PDL 2-3 were only slightly less than those in normal fibroblasts. With increasing PDL, both progeria cell lines exhibited reduction of the UDS levels and undetectable ones at PDL 9-11. Prompt and transient induction of PA was also detectable at less than PDL 5, whereas it was undectable at higher PDL. However, the levels of UDS and PA induction were increased about 3-7 times after pretreatment with 100 IU/ml human interferon (HuIFN)-beta preparations for more than 24 h prior to UV irradiation, although UDS and PA were undetectable at more than PDL 10. These results suggest that cytokines such as HuIFN-beta transiently compensate for the decreases in UDS and PA inducibility in progeria cells with aging. PMID- 7862177 TI - N-nitrosomethylurea-induced carcinogenesis in the progeny of male rats of different ages. AB - Three-month-old male and 3-month-old female LIO rats as well as 25-month-old males and 3-month-old females were mated and at the age of 3 months their progeny were exposed to a single intravenous injection of N-nitrosomethylurea (MNU) at the dose of 20 mg/kg of body weight or solvent. Animals were under observation during 18 months after injection of the carcinogen. There was no significant difference in spontaneous tumor incidence between progeny of young and old male rats. At the same time, the susceptibility to the carcinogenic effect of NMU in the male and female progeny of old males was slightly but significantly increased in comparison to the progeny of young males. Mesenchymal kidney tumors were discovered in the NMU-treated male progeny of old males but not in the male progeny of young male rats. In females, the incidence of mesenchymal kidney tumors in the NMU-treated progeny of young and old males was 7% and 20%, respectively, and the mean survival times of these tumor-bearing rats was 4 months shorter in the last group. The data obtained are in agreement with the observation on germ-line transgeneration transmission of predisposition to carcinogenesis. PMID- 7862178 TI - A population-based serologic survey of immunity to tetanus in the United States. AB - BACKGROUND: Vaccination rates are frequently considered a surrogate measure of protection. To provide more accurate estimates, serum levels of antibody against tetanus were measured as part of the third National Health and Nutrition Examination Survey (NHANES III), which studied a representative sample of the civilian, noninstitutionalized population of the United States. METHODS: We measured tetanus antitoxin using a solid-phase enzyme immunoassay in serum samples from 10,618 persons six years of age and older who were examined during phase 1 of NHANES III in 1988 to 1991. RESULTS: Overall, 69.7 percent of Americans six years of age and older had protective levels of tetanus antibodies (> 0.15 IU per milliliter). The rate decreased from 87.7 percent among those 6 to 11 years of age to 27.8 percent among those 70 years of age or older. Among children 6 to 16 years of age, 82.2 percent had protective levels of tetanus antibodies, with little variation according to race or ethnicity. More men than women were immune (79.0 percent vs. 62.4 percent). Mexican Americans had a significantly lower rate of immunity (57.9 percent, P < 0.05) than either non Hispanic whites (72.7 percent) or non-Hispanic blacks (68.1 percent). Those with a history of military service, higher levels of education, or incomes above the poverty level were more likely to have protective antibody levels. Although the prevalence of immunity declined rapidly starting at the age of 40 years, most of the 107 cases of tetanus (with 20 deaths) reported in 1989 and 1990 occurred in persons 60 years of age or older. CONCLUSIONS: Despite the fact that effective vaccines against tetanus have been available since the 1940s, many Americans do not have immunity to tetanus, and the rates are lowest among the elderly. There is an excellent correlation between vaccination rates (96 percent) and immunity (96 percent) among six-year-olds. However, antibody levels decline over time, and one fifth of older children (10 to 16 years of age) do not have protective antibody levels. PMID- 7862179 TI - Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. AB - BACKGROUND: Many risk factors for hip fractures have been suggested but have not been evaluated in a comprehensive prospective study. METHODS: We assessed potential risk factors, including bone mass, in 9516 white women 65 years of age or older who had had no previous hip fracture. We then followed these women at 4 month intervals for an average of 4.1 years to determine the frequency of hip fracture. All reports of hip fractures were validated by review of x-ray films. RESULTS: During the follow-up period, 192 women had first hip fractures not due to motor vehicle accidents. In multivariable age-adjusted analyses, a maternal history of hip fracture doubled the risk of hip fracture (relative risk, 2.0; 95 percent confidence interval, 1.4 to 2.9), and the increase in risk remained significant after adjustment for bone density. Women who had gained weight since the age of 25 had a lower risk. The risk was higher among women who had previous fractures of any type after the age of 50, were tall at the age of 25, rated their own health as fair or poor, had previous hyperthyroidism, had been treated with long-acting benzodiazepines or anticonvulsant drugs, ingested greater amounts of caffeine, or spent four hours a day or less on their feet. Examination findings associated with an increased risk included the inability to rise from a chair without using one's arms, poor depth perception, poor contrast sensitivity, and tachycardia at rest. Low calcaneal bone density was also an independent risk factor. The incidence of hip fracture ranged from 1.1 (95 percent confidence interval, 0.5 to 1.6) per 1,000 woman-years among women with no more than two risk factors and normal calcaneal bone density for their age to 27 (95 percent confidence interval, 20 to 34) per 1,000 woman-years among those with five or more risk factors and bone density in the lowest third for their age. CONCLUSIONS: Women with multiple risk factors and low bone density have an especially high risk of hip fracture. Maintaining body weight, walking for exercise, avoiding long-acting benzodiazepines, minimizing caffeine intake, and treating impaired visual function are among the steps that may decrease the risk. PMID- 7862180 TI - Intrasphincteric botulinum toxin for the treatment of achalasia. AB - BACKGROUND: Achalasia is a disorder of swallowing in which the lower esophageal sphincter fails to relax. We report the use of botulinum toxin, a paralytic agent, for the treatment of this condition. METHODS: In a double-blind trial, 21 patients with achalasia received either 80 units of botulinum toxin or placebo, injected endoscopically into the lower esophageal sphincter. One week later, the response to treatment was assessed on the basis of changes in the symptom scores (measured on a scale from 0 to 9), pharyngoesophagograms, and results of esophageal manometric and scintigraphic studies. Patients who received placebo initially were subsequently treated with botulinum toxin. After six months, esophageal scintigraphy was repeated. RESULTS: One week after treatment, the mean decrease in the symptom score was 5.4 points for the patients treated with botulinum toxin and 0.5 point for the placebo group (P = 0.001). The mean decrease in the pressure of the lower esophageal sphincter was 33 percent in the treatment group, as compared with a mean increase of 12 percent in the placebo group (P = 0.02), and the mean increase in the width of the opening of the lower esophageal sphincter was 204 percent in the treatment group, as compared with a mean decrease of 14 percent in the placebo group (P = 0.02). Nineteen of the 21 patients treated with botulinum toxin had symptomatic improvement initially; after six months 14 patients were still in remission. This improvement was accompanied by a decrease in esophageal retention that was sustained at six months (46 percent, as compared with a pretreatment value of 77 percent; P = 0.04). There were no serious adverse effects. CONCLUSIONS: Injection of botulinum toxin into the lower esophageal sphincter is an effective, safe, and simple method of treatment for achalasia, with results that are sustained for several months. PMID- 7862181 TI - Pulmonary tuberculosis in HIV-infected patients in Zaire. A controlled trial of treatment for either 6 or 12 months. AB - BACKGROUND: We studied the efficacy of a short-course regimen of chemotherapy for pulmonary tuberculosis in Kinshasa, Zaire. We also assessed whether, among patients with human immunodeficiency virus (HIV) infection, treatment should be extended from 6 to 12 months. METHODS: HIV-seropositive and HIV-seronegative outpatients with pulmonary tuberculosis were treated with rifampin, isoniazid, pyrazinamide, and ethambutol daily for two months, followed by rifampin plus isoniazid twice weekly for four months. The HIV-positive patients who had no evidence of tuberculosis were then randomly assigned to receive either rifampin plus isoniazid or placebo twice weekly for a further six months. We also followed a comparison group of HIV-seronegative patients who received no further treatment for tuberculosis after six months. RESULTS: After six months, 260 of 335 HIV seropositive and 186 of 188 HIV-seronegative participants could be evaluated, and their rates of treatment failure were similar: 3.8 and 2.7 percent, respectively. At 24 months, the HIV-seropositive patients who received extended treatment had a relapse rate of 1.9 percent, as compared with 9 percent among the HIV seropositive patients who received placebo for the second 6 months (P < 0.01). Extended treatment did not improve survival, however. Among the HIV-seronegative patients, 5.3 percent relapsed. CONCLUSIONS: Among HIV-seropositive patients with pulmonary tuberculosis, extending treatment from 6 to 12 months reduces the rate of relapse but does not improve survival. The six-month program of partly intermittent antituberculous treatment may be an acceptable alternative when resources are limited. PMID- 7862182 TI - Images in clinical medicine. Transfer of a toe to the hand. PMID- 7862183 TI - Prophylaxis against Pneumocystis carinii pneumonia among children with perinatally acquired human immunodeficiency virus infection in the United States. Pneumocystis carinii Pneumonia Prophylaxis Evaluation Working Group. AB - BACKGROUND: Pneumocystis carinii pneumonia (PCP) remains a common and often fatal opportunistic infection among children infected with the human immunodeficiency virus (HIV). HIV-infected infants between three and six months of age are particularly vulnerable. Current guidelines recommend prophylaxis in children from birth to 11 months old who have CD4+ counts below 1500 cells per cubic millimeter. METHODS: We used national surveillance data to estimate the annual incidence of PCP among children less than one year old. We reviewed the medical records of 300 children given a diagnosis of PCP between January 1991 and June 1993 to determine why treatment according to the 1991 guidelines for prophylaxis against PCP either was not given or failed to prevent the disease. RESULTS: In our study the incidence of PCP in the first year of life among infants born to HIV-infected mothers changed little between 1989 and 1992. Among 7080 children born to HIV-infected mothers in 1992, PCP developed in 2.4 percent. Of 300 children with PCP diagnosed from January 1991 through June 1993, 199 (66 percent) had never received prophylaxis, and for 118 of those children (59 percent) exposure to HIV was first identified 30 days or less before the diagnosis of PCP. Among 129 children less than one year old, the CD4+ count declined by an estimated 967 cells per cubic millimeter (95 percent confidence interval, 724 to 1210 cells per cubic millimeter) during the three months before the diagnosis of PCP. Among infants in whom CD4+ counts were determined within one month of the diagnosis of PCP, 18 percent (20 of 113) had at least 1500 cells per cubic millimeter, a level higher than the currently recommended threshold for prophylaxis. CONCLUSIONS: In the United States the incidence of PCP among HIV infected infants has not declined. If this infection is to be prevented, infants exposed to HIV must be identified earlier, and prophylaxis must be offered to more children than the guidelines currently recommend. PMID- 7862184 TI - Cushing's syndrome. AB - Cushing's syndrome is usually caused by the secretion of corticotropin or cortisol by a pituitary or adrenal tumor, respectively, or by ectopic secretion of corticotropin. It is possible to determine the specific abnormality in most patients, but it can sometimes be difficult to decide whether the patient has hypercortisolism and whether it is primary or due to major depressive disorder or to the stress of other diseases. Determining the cause of the hypercortisolism involves performing multiple tests in a logical sequence; the results should all be consistent with the same diagnosis. Treatment should aim to cure the hypercortisolism and to eliminate any tumor that threatens the patient's health, while minimizing the chance of an endocrine deficiency or long-term dependence on medications. PMID- 7862185 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 9-1995. A 60-year-old man with hypertrophic cardiomyopathy and ischemic colitis. PMID- 7862186 TI - Tetanus--forgotten but not gone. PMID- 7862187 TI - Risk factors for hip fracture. PMID- 7862188 TI - Treatment of achalasia--from whalebone to botulinum toxin. PMID- 7862189 TI - Boosting cardiac contractility with genes. PMID- 7862190 TI - Norplant. PMID- 7862191 TI - Norplant. PMID- 7862192 TI - Knee-replacement surgery in the United States and Ontario. PMID- 7862193 TI - Access to bone marrow transplantation for chronic myeloid leukemia. PMID- 7862194 TI - Treatment of acute lymphoblastic leukemia in a second remission. PMID- 7862195 TI - Treatment of achalasia in Chagas' disease with botulinum toxin. PMID- 7862196 TI - Maternal-fetal transmission of Pneumocystis carinii in human immunodeficiency virus infection. PMID- 7862197 TI - Legislating clean air. Politics, pre-emption, and the health of the public. PMID- 7862198 TI - The role of organized medicine and the American Medical Association in tobacco control. PMID- 7862199 TI - The Tobacco Control Task Force of the North Carolina Medical Society. PMID- 7862200 TI - An interview with Dr. Alan Blum. Tobacco industry nemesis. Interview by Adam Goldstein. PMID- 7862201 TI - How important is tobacco in NC? Facts belie public perception. PMID- 7862202 TI - Giving up smoking. A personal guide to becoming smoke-free. PMID- 7862203 TI - A view from the fields. PMID- 7862204 TI - Tobacco control. If not now, when? PMID- 7862205 TI - Nicotine withdrawal symptoms. A review for primary care practitioners. PMID- 7862206 TI - Nicotine as a therapeutic drug. AB - Current evidence about the therapeutic potential of nicotine is strongest for ulcerative colitis. The role, if any, of nicotine therapy in Parkinson's or Alzheimer's diseases is not clear, but further research appears warranted. We need more information about the tolerability and safety of nicotine administration in such diseases. At present, any therapeutic trials of nicotine therapy should occur only as part of research protocols. Further nonjudgmental examination of the perceived effects of tobacco use may lead to other uses of nicotine. However, given the widespread morbidity and mortality directly attributable to tobacco use, no form of tobacco should be used to deliver nicotine. We encourage everyone who uses tobacco products to quit. PMID- 7862207 TI - Smoking cessation. Cornerstone of prevention in primary care. PMID- 7862208 TI - North Carolina Project ASSIST. A call to action. PMID- 7862209 TI - Illegal sales of cigarettes to minors in North Carolina. PMID- 7862210 TI - Tobacco-free youth. Expanding focus group networks. PMID- 7862211 TI - The prevalence of smoking and its impact on the health of North Carolinians. PMID- 7862212 TI - [Delirium in the nursing home]. PMID- 7862213 TI - [Current viewpoints in the treatment of autoimmune thrombocytopenia in adults]. PMID- 7862214 TI - [Administration of euthanasia-inducing agents]. PMID- 7862215 TI - [Point of departure for a non-resuscitation policy]. PMID- 7862216 TI - [Favorable results of paclitaxel (Taxol) in patients with ovary carcinoma pretreated with platinum]. AB - OBJECTIVE: To assess the anti-tumour and side effects of paclitaxel in patients with ovarian carcinoma, after prior treatment with al least one platinum containing chemotherapy regimen. DESIGN: Phase II study. SETTING: Academic Hospital of the Free University, Amsterdam. METHOD: Fourteen of 55 patients with progressive ovarian carcinoma were treated with 135 mg/m2 and 41 with 175 mg/m2 paclitaxel. 9 patients by 24-hour and 46 by 3-hour intravenous infusion. RESULTS: In 9/55 (16%) patients an objective tumour response was obtained, which was complete in 1 patient. In 19/55 (35%) patients the disease stabilised. The serum CA 125 level was increased in 52 patients. In 33% of the patients the course of the serum CA 125 was an indication of the tumour response. The median duration of response was 8 months (range 4.1-13.1) and the median duration of survival was 11.3 months (range 0.3-28.2). Side effects of paclitaxel treatment were hair loss, arthralgia and myalgia and neutropenia of short duration. In 76% of patients pre-existing neurosensory symptoms increased mildly or developed de novo. The neurotoxic effect appeared reversible in most instances after discontinuation of the paclitaxel treatment. CONCLUSION: In this rather unfavourable patient population, paclitaxel induced only 16% objective response. However, more than 50% of the patients did benefit from paclitaxel treatment, as a much larger group had long lasting disease stabilisation without symptoms or had reduction of symptoms. The treatment was well tolerated by most patients. PMID- 7862217 TI - [Hypertension diagnosis by the family physician: measurements according to the NHG-standard (Dutch College of General Practitioners) compared with ambulatory blood pressure determination]. AB - OBJECTIVE: To compare the standard procedure (SP) for determining hypertension as described by the DCGP with the results of ambulatory blood pressure measurement (ABM). DESIGN: Prospective study. SETTING: Practices of 17 GPs in central and south Limburg, the Netherlands. METHOD: The SP of the DCGP was executed in 94 of 102 patients with possible hypertension. In each patient a 24-hour ABM was performed simultaneously as reference value. RESULTS: The correlation between the SP and the ABM was low (r = 0.51) and the blood pressure was mostly overestimated by the SP. Sensitivity and specificity of the SP were 0.67 and 0.52 respectively. When the first blood pressure measurement was high in a patient with probable hypertension (diastolic pressure 105-115 mmHg) SP correlated well with ABM. When the first blood pressure measured was relatively low (diastolic pressure 95-105 mmHg) correlation was also low. CONCLUSION: The difference in blood pressure measured by the physician in his office compared with measurement at home ('white coat effect') was observed in this study also. The results support the advice of the DCGP to check the blood pressure more often in hypertensive patients with low than in those with high initial diastolic values. PMID- 7862218 TI - [Epidemic of penicillinase-producing, tetracycline-resistant gonococci; risk factors for their spread]. AB - OBJECTIVE: To assess whether the 1989 epidemic of tetracycline-resistant (TRNG) and penicillinase-producing Neisseria gonorrhoeae (PPNG) was caused by a small number of imported strains, and what the risk factors for infection were. DESIGN: Retrospective. SETTING: The National Institute of Public Health and Environmental Protection (NIPHEP). METHOD: A total of 1257 questionnaires were sent to the 5 microbiological laboratories which had contributed most to the number of isolates sent to NIPHEP, in order to obtain additional information of all patients infected in 1989 and 1990 with PPNG. Of all these patients the results of quantitative sensitivity testing, auxotype, serotype and plasmid pattern of the PPNG were obtained. RESULTS: The questionnaire response was 1047/1257 (83.3%). A part of the isolates from the non-responders was included in the study. Determinations were performed in 1185 PPNG isolates (94.3%). In 1988 and 1989 an increase of TRNG among PPNG was observed. The PPNG isolates in 1989 (n - 472) and 1990 (n = 713) from 5 laboratories in Amsterdam. Rotterdam and The Hague, showed that the epidemic was caused mainly by the spread of three strains. NR/IB-6, PRO/IA-3 and PRO/IA-6. The introduction probably took place in The Hague in 1988 and import from abroad could not be confirmed. The TRNG risk was increased for men and women over 40 years and for men from The Hague and Rotterdam having contacts with prostitutes; the latter did not apply to Amsterdam. For women, a Turkish or Latin American nationality increased the TRNG risk. CONCLUSION: Because of the continuing threat of developing resistance and the instability of microbiological characteristics of gonococci, a continuous national surveillance is necessary, including information about risk factors for infection with resistant gonococci, to improve the control of the infection. PMID- 7862219 TI - [Supraventricular tachycardia in a pregnant woman with tertiary malaria; a medical experience from the Indonesian period]. AB - A 22-year-old Indonesian woman became ill with fever and chills in the 7th month of her fourth pregnancy. Two days later she complained of palpitations. At admission again two days later, the temperature was 40 degrees C. The heart rate was 175/min. A blood slide contained trophozoites of Plasmodium vivax. The ECG showed an atrioventricular junctional tachycardia. Treatment consisted of 2 intramuscular injections of 0.5 g quinine hydrochloride administered with an interval of 4 hours. The following morning the temperature was normal and the heart rate had fallen to 100/min. The ECG showed a sinus rhythm. Further therapy consisted of 1.2 g quinine sulphate daily. This case does not support the view that pregnancy may predispose to a paroxysm of tachycardia. It is noteworthy that in this patient 1 gram of quinine hydrochloride not only controlled a malaria attack but also terminated a paroxysm of tachycardia. PMID- 7862220 TI - [Stokvis and psychosomatics]. PMID- 7862221 TI - [Head and brain injuries in adults]. PMID- 7862222 TI - Health care issues in the 1995. Session of the Nebraska legislature. PMID- 7862223 TI - "Do-not-resuscitate" orders for children. PMID- 7862224 TI - Pediatric care in two Nebraska hospital market areas. PMID- 7862225 TI - [Molecular pathology of type 1 primary hyperoxaluria]. AB - Type 1 is the most common form of primary hyperoxaluria, also called oxalosis when systemic involvement has occurred. This recessive autosomal inherited inborn error of metabolism is characterized by a defect of alanine: glyoxylate aminotransferase (AGT), which is a specific liver enzyme. This protein is responsible for glyoxylate detoxification only when it is located in the peroxisome. The clinical and biochemical phenotypes are neither correlated with the residual catalytic activity of AGT nor with its immunoreactivity. Most patients display less than 2% catalytic activity (enz-) or no immunoreactive protein (crm-); peroxisome-to-mitochondrion mistargeting is the main feature of patients crm+/enz+ or crm+/enz-. The cDNA and genomic DNA have been cloned and sequenced and the gene has been located on the long arm of chromosome 2 in the q36-37 region. Three polymorphisms have been identified which are preferentially associated, leading to two alleles; six point mutations have been currently reported. PMID- 7862226 TI - [Kidney transplantation in patients more than 60 years old. Analysis of results apropos of 57 patients]. AB - From April 1988 to August 1993, 57 elderly recipients more than 60 years old (mean age 64 +/- 3 years, 35 males, 22 females) underwent cadaveric renal transplantation. The pretransplant screening included immunological and viral status and urological examination; cardiovascular risk factors were systematically estimated by medical history, physical examination, echocardiography, femoral arterial doppler, and myocardial stress thallium imaging. A coronarography was performed if myocardial ischemia was evidenced. Patients free of cardiovascular diseases or after correction of vascular and/or coronary lesions were included in the waiting list. A sequential immunosuppression regimen including azathioprine, prednisolone anad antilymphocyte globulins was given in all patients. Oral cyclosporin A (5-8 mg/kg/day) was started when serum creatinine level decreased to 200 mumol/l; antilymphocyte globulins were stopped when whole trough blood cyclosporin level reached 150-200 ng/ml. After 24 months of follow-up, the patient survival rate of elderly recipients was significantly lower than the survival rate observed in patients less than 60 years old (90% vs 97%; p < 0.005); the deaths were related to cardiovascular complications in 3 cases and to infectious diseases in 3 cases. No abdominal complications were observed in our series. The graft survival was identical in both groups (81% vs 82% at 2 years), and we observed a low incidence of acute rejection (23%) in the elderly group. The graft function, as determined by serum creatinine level, is significantly correlated with the donor age (p < 0.05). We conclude that the patients more than 60 years old, free of ischemic coronary disease or after correction of such a lesion could be safely transplanted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862227 TI - [Renal pathology in the Ivory Coast: exploration and functional activity of antithrombin iii]. AB - Antithrombin III activity was determined in 96 ivorian adults clinically divided into 3 groups: I) nephrotic syndrome, II) chronic renal failure, and III) terminal uremia requiring maintenance dialysis. In the nephrotic syndrome, a significative decrease of antithrombin III is found, which can explain the existence of thrombotic complications. In chronic renal failure and terminal uremia, antithrombin III activity is normal, and thromboembolic events may be related to a deficiency of other inhibitors of the coagulation. PMID- 7862228 TI - [Renal involvement in POEMS syndrome]. AB - We described a patient with a POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal grammapathy and Skin changes) who was found to have renal involvement with peculiar renal pathological findings. Hitherto, 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 HTA, 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 evoke by light microscopy a MPGN. By immunofluorescent microscopy, no immunoglobulins or complement deposits are found. The finding of mesangiolytic lesions has led to the term of "mesangiolytic glomerulonephritis". The presence, on electron microscopy, of lucent subendothelial space could evoke TMA. But there is neither thrombi, nor arteriolar changes. We are inclined to presume that microangiopathic lesions are due to chronic injury of glomerular endothelial cells, exacerbated at outbreaks of the disease. An increased production of IL-6 could support the efficacity of corticosteroid therapy, particularly in acute clinical situations. PMID- 7862229 TI - [Optimization of enoxaparin dose in the prevention of coagulation in the circuits of hemodialysis: results of a multicenter study]. AB - In order to define the optimal dosage of a low molecular weight enoxaparine (Lovenox) in the prevention of clotting in extracorporeal circulation during hemodialysis, a multicentre trial was conducted in 72 patients dialysed in seven hemodialysis units. During three weeks, these patients received as antithrombic treatment a single injection of enoxaparine at the beginning of the session. The initial dose fixed by previous data concerning dialysis with high hemorrhagic risks patients was 0.5 mg/kg (50 U1 Anti-Xa/kg). According to the evaluation of thrombotic manifestations during a 4 hour dialysis, the dosage was progressively increased if necessary for each patient. For 41% patients, the initial dose of 0.5 mg/kg was maintained along the whole study; 59% patients needed higher dose, between 0.6 and 0.9 mg/kg. The mean dose for the whole patient population at the end of the study was 0.62 +/- 0.16 mg/kg. No complication nor side effect was noted. The influence of blood flow, nature of dialysis membrane, level of hematocrit was studied. In conclusion, 0.5 mg/kg of enoxaparine can prevent thrombotic manifestations in almost half of chronic hemodialysed patients with good results. Further studies could precise the place of personal or technical parameters in the choice of the optimal dose for each patient. PMID- 7862230 TI - [Colloquium on kidney physiology. Paris, 9-10 June 1994. Abstracts]. PMID- 7862231 TI - [Prevalence of certain risk factors in lacunar strokes as compared with cortico subcortical strokes]. AB - Clinical records were reviewed to analyse occurrence of hypertension and other risk factors that may predispose to the development of lacunar stroke. The comparison of risk factors associated with deep, small, ischaemic lesions of the brain (revealed in 67% by CT, in 31% by MRI and in 2% by autopsy) and large superficial or superficial and deep ischaemic lesions (diagnosed in 89% by CT, 4% by MRI and 7% by autopsy) was done. Hypertension, treated and untreated, was more frequent in lacunar stroke, but the difference was not statistically significant. Statistically significant difference was found in large stenotic lesions of internal carotid artery, which were more common in patients with large superficial or superficial and deep lesions (watershed area) and in moderate stenotic lesions of internal carotid artery, which were more common in patients with lacunar stroke. The results suggests that lacunar stroke may be caused by cerebral embolism from carotid sources. PMID- 7862232 TI - [Ganglioside GM1 in early strokes]. AB - The study was taken up to compare the effect of treatment with ganglioside GM1 (Sygen, FIDIA-Italy) and typical treatment in the course of the disease. The study included 98 patients aged 40-82 in good or moderately good physical condition, with the ischaemic stroke confirmed by CT scan, in early stage of stroke (within 48 hours after onset). Patients with severe physical diseases were excluded. The patients were divided at random into two groups. Group I (50 patients) was treated typically and group II (48 patients) was given both typical treatment and ganglioside GM1 administered in 100 mg daily doses over 30 days, i.v. during first 5 days, then i.m. The neurological state was assessed according to the Canadian Neurological Scale (CNS), general fitness according to the Ranking Classification of Neurologic Disability Status (RS) at the admission and after 30 days of the treatment. After 30 days of the treatment no difference between the two groups was found in: 1) mortality, 2) mean survival time, 3) neurological state, 4) patient general fitness. According to the above results the beneficial influence of Sygen treatment of ischaemic stroke was not confirmed. PMID- 7862233 TI - [Dermatomal somatosensory evoked potentials from L3, L4, L5 and S1 spinal roots in healthy subjects]. AB - Dermatomal somatosensory evoked potentials (DSEPs) were recorded in 62 healthy volunteers aged from 15 to 65 years (mean 36.8 +/- 12.9 years) with height from 1.5 to 1.92m (mean 1.69 +/- 0.10m). The aim of the study was to establish normal values for L3, L4, L5 and S1 dermatomes and to introduce this method for the neurophysiological diagnosis of chronic lumbosacral pain and disc disease. The signature areas of dermatomes in both legs separately were stimulated according to the method described by Sedgwick and Katifi (1985). DSEPs were recorded from the scalp electrodes placed at Cz', referred to Fpz. The latencies and amplitudes of consecutive components of DSEPs: N33, P40, N50, P60, N75 and side to side differences were measured and evaluated. Statistical analysis of the results revealed significant positive correlation of DSEPs latencies as a function of height. The correlation of amplitudes with height was less significant. Age, on other hand, showed only negative correlation with amplitudes of later DSEP components. On the basis of the performed analysis the latency of P40 and amplitude of P40-N50 seem to be the best parameters for the evaluation of pathological DSEPs. The range of normal value of latencies for stimulated roots should be calculated from regression equation with the subject's height. As regards amplitude, side to side mean value difference above two standard deviation appears to be more useful. PMID- 7862234 TI - [Double discharges of motor unit -- importance in electromyographic diagnosis]. AB - The prevalence of double-discharge motor unit potentials (DD) in patients with neuromuscular disorders was analysed. Concentric needle electromyography was performed in 29 cases of spinal muscular atrophy (SMA), 25 cases of amyotrophic lateral sclerosis (ALS), 30 cases of Duchenne muscular dystrophy (DMD) and in 20 healthy controls. The DD were recorded only in the patients with neurogenic lesion, mainly in the ALS group. The diagnostic yield of DD in early detection of neurogenic lesion is discussed. PMID- 7862235 TI - [Clinical and electrophysiological examination of brachial plexus in females after radiotherapy and surgical treatment for breast cancer]. AB - Clinical and electrophysiological examinations of the brachial plexus was carried out in 61 women after radiotherapy following operation for breast cancer. A number of clinical abnormalities were found such as hypeaesthesia, hyporeflexia, muscular atrophy, lymphoedema of the extremity which were confirmed by electrophysiological examination. The most common findings were of neurogenic muscular atrophy in the involved extremity, less frequent was slower nerve conduction on the affected side. The analysis of the results suggested mixed type of brachial plexus lesions diagnosed in these cases as late brachial plexopathy. PMID- 7862236 TI - [Chemonucleolysis in the treatment of lumbar discopathy]. AB - The authors describe the method of non-operative treatment of widely occurring low back pain syndromes diagnosed as due to isolated degeneration of the nucleus pulposus. In this phase of degenerative spinal disease pain is not due to nucleus pulposus prolapse. The patients are dissatisfied with the results of physiotherapy and rehabilitation, and surgical treatment brings no satisfactory results. The method of dissolving of nucleus pulposus, widely used in the USA, Australia and West European countries, has been used in Poland only in the clinical centre of the authors. The clinical experience gathered during these years made possible delineation of the syndrome of isolated nucleus pulposus degeneration and strict qualification for chemonucleolysis which gives success in about 90% of cases. PMID- 7862237 TI - [Early results of surgical treatment of chronic subdural hematoma in CT images]. AB - Since the introduction of CT it has become possible to trace the pattern of brain changes after removal of subdural haematoma. Postoperative studies show frequently presence of haematoma residues, and this is connected with the problem of deciding about establishing of indications to reoperation, especially difficult if the patient is in a good clinical condition. The clinical status was compared with CT findings preoperatively and postoperatively in 20 patients subjected to operations for chronic subdural haematomas. A statistically significant correlation was found between the size of the mass effect in CT before and after the operation and the severity of the clinical condition. Major mass effect with high-grade ventricular shifting is more frequently connected with partially haemolysed haematoma in CT. The thickness of subdural haematoma exceeding 20 mm correlated with severe clinical condition, and increased the probability of hemiparesis persistence after the operation. Finding of residual haematoma in CT imaging after the operation, especially when not associated with high-grade mass effect, and with good clinical condition should not be accepted as an indication to repeated operation. In the presented material out of 15 patients with good clinical condition 12 had CT evidence of residual haematoma, and only one had reoperation in view of persisting evident mass effect. PMID- 7862238 TI - [The prognostic values and correlations between Hockaday's (EEG) and Nathanson Bergman's (ENG) scales in the context of new definition of death]. AB - A group of 92 patients being under treatment in Intensive Care Unit of Neurosurgery Clinic in Bydgoszcz were observed using EEG, ENG and neurological findings. The eeg patterns, classified by Hockaday's scale, were related to the clinical stage, described using Glasgow Coma Scale, and the ENG patterns (Nathanson-Bergman's scale). Unfavourable prognosis was indicated by appearance of IV and V stage on Hockaday's scale and the caloric test seemed to mark the moment of complete breakdown of all brain-stem functions. The present paper demonstrated the value of EEG- and ENG patterns in description and forecasting of patients in coma. PMID- 7862239 TI - [Results of combined treatment of cerebellar medulloblastomas in children with chemotherapy preceding radiotherapy]. AB - 153 patients presenting with medulloblastoma between 1980-1992 were treated at the Department of Pediatric Neurosurgery, Child's Health Centre in Warszawa. This group was studied retrospectively and assessed for clinical presentation, histology, treatment regimen and survival. 44 cases treated between 1980 and 1986 underwent surgical resection, postoperative staging evaluation, and craniospinal irradiation, additionally patients assigned to "high risk" group received post irradiation chemotherapy. Beginning 1986-86 patients with "standard risk" medulloblastoma were treated with preirradiation--"sandwich" chemotherapy consisting of either procarbazine, vincristine and CCNU or "eight drugs a day", followed by megavoltage irradiation, while "high risk" group received also postirradiation chemotherapy. The 5-year actuarial survival rate for all patients was 43%. There were no statistically significant differences in 5-year survival rate between the group treated with preirradiation chemotherapy--52%, and without -54%. The presented group was studied to identify variables of prognostic significance. The extent of disease at the time of diagnosis, as measured by M staging criteria was significantly associated with outcome. The extent of tumour resection, histological subtype of the tumour, postoperative complications, T staging, and age did not influence the prognosis in the present study. PMID- 7862240 TI - [The importance of transoesophageal echocardiography in establishing of the source of cerebral embolism]. AB - Transesophageal echocardiography becomes widely used in patients suspected of cerebral embolism. This examination is characterized by higher than transthoracic echocardiography sensitivity for detection of left atrial thrombus. Patent foramen ovale and atrial septal aneurysm have been recognized more often in patients with embolic stroke than in control group. Another potential source of embolism is aortic atheroma especially when protruding or ulcerated. Transesophageal echocardiography allows for identification of embolic source in more than 50% of examined patients. PMID- 7862241 TI - [Computerized system for multichannel recording of analog signals in intensive neurosurgical care]. AB - Modern intensive neurosurgical care is connected with the necessity of perception by the personnel of a great number of information from several monitored patients. This requires using sensors of various physical values and appropriate measuring and signalling systems. For avoiding of high costs connected with the use of specialized equipment, and for precise adjustment of the recording systems for specific use a PC-class computer with eight-channel chart of analog-digital transducer was used, together with a programme for collection, transduction and visualization of the recorder parameters. Both the transducer chart and the programme are in wide use although fully professional. The price is reasonable and the programme is fully intuitive. The association of computerized recorder with Polish pressure transducers made possible, among other, routine measurement of intracranial pressure in neurosurgical patients. PMID- 7862242 TI - [Central myelinolysis of medulla oblongata. Case report]. AB - A case of multisymptomatic brain stem injury, possibly during subacute viral infection, in a 27-year-old man is reported. Two MR imaging at the time of regression of disease symptoms demonstrated in the medulla stabilized lesions of the type of central myelinolysis without damage to the corticospinal pathways. During four years of follow-up the neurological status was improving gradually, but involuntary movements of the mandible and face muscles make speech difficult. PMID- 7862243 TI - [Neurinoma of trigeminal ganglion]. PMID- 7862244 TI - [A case of coexistence of meningioma with intracranial aneurysm in a patient with ruptured aortal aneurysm]. AB - Fifty-three-year-old woman was admitted to hospital with tetraplegia symptoms and died two hours later. Clinical diagnosis was: cerebral stroke, hypertension in anamnesis. Postmortem examination showed ruptured dissecting aneurysm of thoracic and abdominal segment of aorta, meningioma of right pontocerebellar angle and saccular aneurysm of left inferior, posterior cerebellar artery. The diagnostic difficulties and hypotheses of formation of multifocal of different changes are discussed. PMID- 7862245 TI - [Repeatedly recurrent meningitis after removal of anterior fossa meningioma]. PMID- 7862246 TI - [About an abortion in patients with multiple sclerosis]. PMID- 7862247 TI - m-sulphonate benzene diazonium chloride: a novel GABAA receptor antagonist. AB - A previously identified irreversible affinity label for the gamma-aminobutyric acid (GABA) binding site in rat brain membranes, m-sulphonate benzene diazonium chloride (MSBD), was characterized in functional studies using patch clamp and two-electrode voltage clamp recording techniques. MSBD did not exhibit any agonist activity on native GABAA receptors in cultured sympathetic ganglionic neurones but acted as an antagonist of GABA-induced membrane currents. Recombinant GABAA receptors composed of alpha 1, beta 1 and gamma 2S subunits were expressed in Xenopus oocytes following microinjection with cDNAs. Equilibrium dose-response curve analyses established that MSBD was a partially reversible, apparently non-competitive GABAA receptor antagonist. The IC50 for MSBD was estimated from an inhibition curve as 87 +/- 3 microM. In addition, the onset and recovery from MSBD-induced inhibition was independent of GABAA receptor activation. The relatively simple structure of this novel GABAA receptor antagonist, MSBD, is compared with known agonists and antagonists at the GABAA receptor. MSBD may be a useful pharmacological tool which could be used to deduce further information about the structure and function of agonist and antagonist binding sites on the GABAA receptor. PMID- 7862248 TI - Valproic acid inhibits the depolarizing rectification in neurons of rat amygdala. AB - The actions of valproic acid (VPA) on neuronal membrane properties and synaptic transmission were studied using intracellular recording techniques in rat basolateral neurons of the amygdala slices. In therapeutically attainable concentrations (10-100 microM), VPA decreased synaptically-induced epileptiform bursting in the presence of bicuculline. Additionally, the frequency of repetitive discharge induced by direct superthreshold depolarizing current pulses was decreased by VPA. However, evoked excitatory and inhibitory postsynaptic potentials were not affected at this level of drug concentration. The current voltage relationship of untreated neurons revealed rectification of membrane potential when neuronal membrane was depolarized with cathodal current pulses. This depolarizing rectification was blocked by VPA. High medium calcium or addition of the sodium channel blocker tetrodotoxin (TTX) also blocked the depolarizing rectification, whereas the calcium channel antagonist diltiazem had no effect on the rectification. Elevation of medium calcium concentration also blocked the bicuculline-induced bursting. These results indicate that the inhibition by VPA of subthreshold slow sodium current and membrane depolarizing rectification results in suppression of neuronal membrane excitability which is probably a major mechanism for its anticonvulsant action. PMID- 7862249 TI - Regulation of bradykinin sensitivity in peripheral sensory fibres of the neonatal rat by nitric oxide and cyclic GMP. AB - Bradykinin-induced activation of peripheral sensory fibres was studied using an in vitro preparation of the neonatal rat spinal cord with attached tail. Noxious heat stimulation, as well as the applications of bradykinin and capsaicin, to the tail evoked reproducible responses recorded as a depolarization of a lumbar ventral root. Prolonged administration of a supramaximal concentration of bradykinin invariably induced a complete but selective desensitization to a subsequent bradykinin challenge. Bradykinin-induced desensitization was significantly attenuated by concanavalin-A and the effect of concanavalin-A was prevented by alpha-methyl mannoside. Both cyclic GMP and sodium nitroprusside induced a long lasting reduction of bradykinin responsiveness in peripheral fibres. The effect of nitroprusside was prevented by concanavalin-A, and by methylene blue, an inhibitor of guanylyl cyclase. Methylene blue also reduced bradykinin-induced desensitization. L-arginine, but not D-arginine, induced a desensitization to bradykinin. On the other hand, 7-nitroindazole (7-NI, 200-500 nM), an inhibitor of NOS, reduced the desensitization of bradykinin responses but higher concentrations of 7-NI (IC50 = 6.7 +/- 0.9 microM) selectively attenuated responses to bradykinin. The effects of 7-NI were attenuated by L-arginine pretreatment. These data suggest that bradykinin-induced desensitization of peripheral sensory fibres is mediated in part via NO and cyclic GMP dependent mechanisms: possibly NO production is required for guanylate cyclase activation. PMID- 7862250 TI - Multiple mechanisms for the effects of capsaicin, bradykinin and nicotine on CGRP release from tracheal afferent nerves: role of prostaglandins, sympathetic nerves and mast cells. AB - Application of capsaicin (CAP), bradykinin (BK) or nicotine (NIC) to intraluminally perfused rat tracheas induced an increase in calcitonin gene related peptide (CGRP) levels in the perfusates. Depletion of sensory afferent CGRP with systemic CAP pretreatment resulted in a significant reduction of CGRP release evoked by CAP, BK or NIC. Chemical destruction of sympathetic nerve fibres by systemic pretreatment with 6-hydroxydopamine reduced CGRP release evoked by NIC, but did not alter the release produced by CAP or BK. Elimination of the tracheal mast cell population by pretreatment with compound 48/80 did not alter the effects of CAP, BK or NIC. CGRP release evoked by BK and NIC, but not CAP, was diminished by indomethacin, suggesting that cyclooxygenase products mediate the actions of BK and NIC. Prostaglandins, PGE1, PGE2, PGF2 alpha and PGI2, displayed stimulatory effects on CGRP release in the trachea. There are evidently multiple mechanisms mediating CGRP release from sensory terminals in rat trachea. It appears that CAP exerts a direct action on sensory nerves, while the effects of BK and NIC are mediated by PG synthesis. Sympathetic activation may be involved in NIC, but not BK, induced PG-mediated CGRP release. PMID- 7862251 TI - FR139317, a specific ETA-receptor antagonist, inhibits cerebral activation by intraventricular endothelin-1 in conscious rats. AB - A comprehensive series of time-related behavioral, physiological and cerebral metabolic studies was conducted using conscious Sprague-Dawley rats to discern the anti-endothelin (ET) properties of the specific ETA receptor antagonist, FR139317. Endothelin-1 (9 pmol given by injection into one lateral ventricle, i.c.v.) produced convulsions, acute arterial hypertension, arterial hyperglycemia, and hyperventilation. Brain structures close to the i.c.v. site of injection, such as the caudate nucleus, lateral septal nucleus, corpus callosum and hippocampal CA3 medial lamellae, as well as 14 other individual structures, displayed moderate-to-intense levels of metabolic activation after endothelin. Data were assessed quantitatively by means of the autoradiographic [14C]deoxyglucose technique combined with image analysis. Neural circuits in the efferent projection paths of the stimulated forebrain structures, such as the midbrain oculomotor complex, amygdaloid nuclei, substantia nigra pars reticulata and caudal subicular subregions of the hippocampal formation, were stimulated focally by endothelin. Specific medullary nuclei and cerebellar cortical subregions displayed high rates of glucose metabolism following endothelin injection at the time of maximum behavioral and physiological stimulation. I.c.v. treatment with > or = 14 nmol FR139317 before endothelin significantly inhibited the effects produced by the peptide. At the highest dose of FR139317 (28 nmol), there was only mild behavioral stimulation following endothelin injection, and hypermetabolic responses in the brain were abolished except in two specific areas of the cerebellar cortex (approx 40% increases in metabolic activity in the copula pyramis and paramedian lobule). The results indicate that the cerebral stimulatory effects of i.c.v. endothelin are mediated by the A type of endothelin receptor. By itself, i.c.v. FR139317 had no effects on the parameters assessed. Further evaluation of FR139317 is warranted as a possible therapeutic agent for neuropathologies suspected of deriving from central neural or vascular stimulation by endothelin, such as aneurysmal vasospasm, ischemia, excitotoxicity, and peptide-mediated epilepsies. PMID- 7862252 TI - Comparison of delta opiate receptor agonist induced reward and motor effects between the ventral pallidum and dorsal striatum. AB - The role of the ventral pallidum and the dorsal striatum in mediating the rewarding effects of the delta receptor specific agonist [2-D-penicillamine, 5-D penicillamine]enkephalin (DPDPE) were evaluated in the rat using the intracranial self-stimulation paradigm. Reward shifts were indicated by the change in frequency required to maintain half-maximal responding while motor/performance changes were identified by increases or decreases in the maximum responding. Each hour-long test session consisted of three identical, consecutive 20 min rate frequency curves. In an effort to ascertain possible heterogeneity of function along the rostrocaudal axis, DPDPE (0.0 nmol = saline dose, 0.3 nmol = low dose, 1.0 nmol = medium dose, 3.0 nmol = high dose) was microinjected into either the rostral or caudal region of the two structures. Microinjections into the caudate were positioned directly above the ventral pallidum placements resulting in centromedial or caudomedial caudate placements. DPDPE microinjections into the rostral ventral pallidum resulted in a significant reward increase (28% increase or -0.14 log Hg shift) only at the high dose. In contrast, caudal ventral pallidal DPDPE microinjections showed a dose-response effect with reward increases of 19, 22 and 31% (-0.09, -0.11 and -0.16 log Hz) for the low, medium and high dose, respectively. DPDPE microinjections into the centromedial caudate resulted in a large reward increase (29% or -0.15 log Hz) at the high dose, while caudomedial caudate DPDPE microinjections had no effect on reward. Motor/performance effects tended to follow the pattern of reward effects, with most regions showing motor increases ranging from 25 to 75% over baseline activity. The only exception was found in the caudomedial caudate, where microinjections of the high dose of DPDPE resulted in an approximate 20% suppression of motor/performance activity. These results demonstrate that the ventral pallidum and the mediocentral caudate play a role in modulating opiate rewards, and adds to the growing body of literature regarding the regional heterogeneity within the caudate and ventral pallidum. PMID- 7862253 TI - Effects of TA-0910, an orally active TRH analog, on the spinal reflex in spinal rats. AB - Effects of TA-0910 (1-methyl-(S)-4,5-dihydroorotyl-L-histidyl-L-prolinamide), a new thyrotropin releasing hormone (TRH) analog, on spinal reflex potentials and flexor reflexes were compared with those of TRH in C1-spinal rats. Intravenously administered TA-0910 and TRH produced dose-dependent increases in the amplitudes of mono- and polysynaptic reflex potentials and withdrawal flexor reflexes. TA 0910 was more potent and more long-lasting than TRH. The stimulating actions of TA-0910 and TRH on the monosynaptic reflex potential were not antagonized by pretreatment with atropine, cyproheptadine, haloperidol or prazosin, suggesting no involvement of the cholinergic, serotonergic, dopaminergic or noradrenergic system. Intraduodenally administered TA-0910 also produced a lasting potentiation of the withdrawal flexor reflex, but intraduodenally administered TRH showed no effect. These results suggest that TA-0910 may be a more useful drug than TRH for spinal functional disorders. PMID- 7862254 TI - Structural requirements for the occupancy of rat brain PACAP receptors and adenylate cyclase activation. AB - N-terminally shortened analogues of PACAP(1-27) and PACAP(1-38), and analogues modified in position 1,2 or 3 were compared for their ability to interact with PACAP receptors and to activate or inhibit adenylate cyclase in rat brain hippocampus membranes. In the PACAP(1-27) series, deletion of the first two amino acids decreased the potency 3000-fold. PACAP fragments (3-27) to (9-27) were inactive on the enzyme. N-terminally shortened PACAP(1-38) analogues showed a similar profile but were 70 to 300-fold more potent than their PACAP(1-27) equivalents. PACAP(6-27) and PACAP(6-38) were competitive inhibitors of the PACAP(1-27) stimulated enzyme. The Kd values of PACAP(6-27) and PACAP(6-38) were of 1000 and 2 nM respectively. Surprisingly, the Kd values of PACAP(6-31) and (6 35), that were also unable to stimulate adenylate cyclase activity, were of 3 and 300 nM respectively. Replacement of His1 by Phe1 in PACAP(1-27) reduced the potency 600-fold. Replacement of Ser2 by Ala2 in PACAP(1-27) and PACAP(1-38) was of little consequence. Substitution of Ser2 by Phe2, DPhe2, Arg2 or DArg2 reduced 60 to 1000-fold the PACAP(1-27) potency but only 7 to 30-fold the PACAP(1-38) potency. Phe2 derivatives were inactive on the enzyme. Replacement of Asp3 by Asn reduced 4000-fold the PACAP(1-27) potency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862255 TI - The effect of amflutizole, a xanthine oxidase inhibitor, on ischemia-evoked purine release and free radical formation in the rat cerebral cortex. AB - The efflux of hypoxanthine, xanthine and uric acid into cortical superfusates was studied with the cortical cup technique in the rat. Twenty minutes of four vessel occlusion followed by reperfusion results in a massive increase in the efflux of these purine metabolites. Amflutizole, 10 microM administered topically into the cortical cups, enhanced the ischemia-evoked release of hypoxanthine while it suppressed xanthine formation. Uric acid levels were not affected. Amflutizole also eliminated the ischemia/reperfusion-evoked generation of free radical adducts of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) detected by electron spin resonance. These results are consistent with a block of xanthine oxidase by amflutizole and support the involvement of xanthine oxidase in free radical mediated tissue damage following ischemia/reperfusion. PMID- 7862256 TI - Effect of chronic treatment with ethanol and withdrawal of ethanol on binding of [3H]SCH23390 to D1 dopamine receptor in rat visual cortex and hippocampus. An autoradiographic study. AB - Male Wistar rats, treated with ethanol for 8 weeks and pair-control animals, were used to study the effects of chronic treatment with ethanol, and withdrawal of ethanol for 24 and 48 hr on [3H]SCH23390 binding. The visual cortex (Laminae III IV and Lamina VI), the superficial grey layer of the superior colliculus, and the molecular layer of the dentate gyrus of the hippocampus were the cerebral areas analysed. Non significant changes were observed in hippocampus and Laminae III-IV of the visual cortex after treatments with alcohol. More interesting results were obtained from Lamina VI, where the chronic treatment with ethanol did not modify the binding of [3H]SCH23390, whereas the withdrawal of ethanol produced a statistically significant increase in binding values. In addition, superficial grey layer of the superior colliculus showed a significant increase in binding values between 48 hr withdrawal and ethanol treated groups. The results herein reported suggest that some structures involved in visual functions are related to responses of adaptation to ethanol. PMID- 7862257 TI - Calcium channel antagonist peptides define several components of transmitter release in the hippocampus. AB - The use of subtype-selective voltage-sensitive calcium channel (VSCC) antagonists has established that neurotransmitter release in mammalian brain is mediated by N like and P-like VSCCs, and that other subtypes also contribute significantly. To determine the roles presynaptic VSCCs play in nervous system function and to evaluate the therapeutic potential of their selective inhibition, it is necessary to define further the contributions of VSCC subtypes to neurotransmitter release. The novel conopeptide, SNX-230 (omega-conopeptide MVIIC), has revealed a new VSCC subtype, the Q-type, in cerebellar granule cells. We have compared the effects of SNX-230 on release of tritiated D-aspartate ([3H]D-Asp; a non-metabolizable analog of glutamate), gamma-aminobutyric acid ([3H]GABA), and norepinephrine ([3H]NE) from rat hippocampal slices to those of the N-type VSCC blocker, SNX-111 (omega-conopeptide MVIIA), and the P-type blocker, omega-agatoxin-IVA (AgaIVA). SNX-230 blocks both [3H]D-Asp and [3H]GABA release completely, whereas AgaIVA blocks them potently but partially and SNX-111 has no effect. These results suggest that glutamate and GABA release are mediated by two VSCC subtypes, a P type and another, perhaps Q-like. SNX-111 blocks [3H]NE release potently but partially, while SNX-230 blockade is complete, consisting of one very potent phase and one less potent phase. AgaIVA also blocks [3H]NE release potently but partially. These results suggest that at least two VSCC subtypes, an N-type and a novel non-N-type, mediate NE release. Pair-wise combinations of the three ligands indicate that at least three pharmacologically distinct components comprise [3H]NE release in the hippocampus. PMID- 7862258 TI - Alpha-trinositol blocks the inhibitory effects of NPY on dilatation to forskolin but not the adenylyl cyclase activity induced by NPY or forskolin in guinea-pig cerebral vessels. AB - There is much data showing correlation between forskolin-induced relaxation and production of cyclic AMP. But are these processes coupled or two phenomena occurring in parallel? This question was studied in guinea-pig cerebral vessels by using NPY as a strong inhibitor and alpha-trinositol as its antagonist. The basal cyclic AMP content of cerebral vessel segments in the control group was 670 +/- 53 fmol/mg wet weight (w.w.). Forskolin (10(-7), 3 x 10(-7) and 10(-6) M) increased the formation of cyclic AMP to 738 +/- 86 (ns), 699 +/- 81 (ns) and 1158 +/- 132 fmol/mg w.w. (p < 0.05), respectively. alpha-trinositol (10(-8)-10( 6) M) neither reduced the formation of cyclic AMP compared to basal cyclic AMP levels nor affected the forskolin-stimulated increase of cyclic AMP (p > 0.05). On the other hand, NPY (10(-7) M) not only decreased basal formation of cyclic AMP (p < 0.05) but also attenuated the forskolin-stimulated increase of cyclic AMP (p < 0.005). The inhibitory effects of NPY on both basal levels of cyclic AMP and forskolin-induced increase of cyclic AMP were not reversed by the application of alpha-trinositol (10(-8)-10(-6) M). In studies on vasomotor responses, forskolin (10(-9)-10(-5) M) induced a concentration-dependent relaxation of precontracted guinea-pig basilar arteries. NPY (10(-7) M) shifted the forskolin induced relaxation of the basilar arteries towards higher forskolin concentrations. This inhibitory effect of NPY was reversed by alpha-trinositol (10(-6) M). We conclude that 1) NPY decreases basal and forskolin-stimulated cyclic AMP levels; 2) alpha-trinositol neither reverses the inhibitory effect of NPY on nor modulates basal or forskolin-stimulated cyclic AMP levels; 3) However, the antagonistic effect of NPY on forskolin-induced relaxation is significantly reversed by administration of alpha-trinositol. This demonstrates a dissociation of the dilator effects of forskolin and its generation of cyclic AMP. PMID- 7862259 TI - Pertussis toxin pretreatment enhances catecholamine secretion induced by pituitary adenylate cyclase-activating polypeptide in cultured porcine adrenal medullary chromaffin cells: a possible role of the inositol lipid cascade. AB - We determined how pertussis toxin (PTX) pretreatment alters PACAP-induced catecholamine secretion in cultured porcine adrenal medullary cells. Pretreatment of these cells with PTX (1 ng/ml for 24 h or 10 ng/ml for 6 h) markedly enhanced PACAP-induced catecholamine secretion. PTX pretreatment also produced a small increase in basal secretion and secretion in response to nicotine and carbachol, but the effect of the PACAP-induced secretion was most striking. We examined the role of the phosphoinositol cascade in potentiating the PACAP-induced catecholamine secretion by PTX and found that PACAP-induced accumulation of inositol phosphates in PTX-pretreated cells was significantly greater than that in untreated cells. Furthermore, removal of extracellular Ca2+ and addition of Ca2+ channel blockers inhibited the catecholamine secretion induced by PACAP in PTX-pretreated cells. From these results, we speculate that a PTX-sensitive G protein tonically inhibits phospholipase C. PTX enhances the PACAP-induced secretion of catecholamine by blocking the action of this inhibitory G-protein. PMID- 7862260 TI - Prodynorphin-derived peptide expression in primate cortex and striatum. AB - The distributions of four prodynorphin-derived peptides, dynorphin A (1-17), dynorphin A (1-8), dynorphin B, and alpha-neo-endorphin were determined in 10 cortical regions and the striatum of the old world monkey (Macaca nemestrina). alpha-neo-endorphin was the most abundant peptide in both cortex and striatum. The concentrations of all four peptides were significantly greater in the striatum compared to the cortex. In general, concentrations of each peptide tended to be higher in allocortex than in neocortex. Possible inter- and intradomain processing differences, as estimated by ratios of these peptides, did not vary within cortex, but the intradomain peptide ratio, dyn A (1-17)/dyn A (1 8), was significantly greater in cortex than in striatum. These results indicate that prodynorphin is, in some ways, uniquely processed in the primate. Particularly unusual is the relatively low abundance of prodynorphin-derived products in the cortex, in the face of moderately high levels of kappa opiate receptor expression. PMID- 7862261 TI - Evidence that endogenous vasoactive intestinal peptide (VIP) is involved in the regulation of rat pituitary-adrenocortical function: in vivo studies with a VIP antagonist. AB - The effect of a subcutaneous bolus injection of 2 micrograms magnitude of Ac,Tyr1,D-Phe2-GRF(1-29) amide, a specific VIP antagonist (VIP-A), on the hypothalamo-pituitary-adrenocortical (HPA) axis were investigated in both normal and ether- or cold-stressed rats. Blood concentrations of ACTH, aldosterone (ALDO) and corticosterone (B) were measured by specific RIA 1, 2 or 4 h after VIP A injection. VIP-A administration to normal rats strikingly lowered the plasma concentration of ALDO, without significantly affecting those of ACTH and B. Ether and cold stresses notably raised the blood levels of ACTH, ALDO and B, and these rises lasted unchanged until 4 h. VIP-A did not affect the response of HPA axis to ether stress, but provoked a marked depression of that to cold stress. In light of these findings the following conclusions can be drawn: (i) endogenous VIP does not regulate HPA-axis function under basal conditions, but it plays a pivotal role in the mechanisms involved in the activation of HPA axis induced by cold exposure; and (ii) endogenous VIP exerts a tonic stimulatory action on ALDO secretion, probably by acting directly on the adrenal zona glomerulosa. PMID- 7862262 TI - Delirium and the dexamethasone suppression test in the elderly. AB - It has been suggested that delirium in the elderly is caused by abnormally high levels of circulating glucocorticoids or by an increased vulnerability to their effects. We performed a dexamethasone suppression test (DST) in 16 consecutive patients without depression or dementia admitted to an acute-care geriatric unit with a clinical diagnosis of lower respiratory tract infection. Seven of 9 (78%) patients who developed delirium were non-suppressors on the DST compared with 1 of 7 (14%) patients without delirium (p = 0.04). Clinical and laboratory indicators of the severity of illness did not differ between the two groups. Of the 8 patients with an abnormal DST, 1 died and another was not available for repeat assessment. On re-examination 8 weeks later, after resolution of the delirium and of the chest infection, 5 of 6 non-suppressors still had an abnormal DST. It is known that some non-demented and non-depressed elderly patients fail to suppress cortisol in response to 1 mg of dexamethasone. Our results suggest that such patients may be at increased risk for developing delirium during acute illness. PMID- 7862263 TI - Schizophrenia and autoimmunity--a possible etiological mechanism? AB - Schizophrenia is a chronic disease which begins during early adulthood and persists throughout life. It may appear in two main clinical patterns: chronic progressive and relapsing-remitting. The diagnosis is based entirely on clinical data, as no auxiliary laboratory tests are available. Schizophrenia has a heterogeneous clinical expression which may reflect different etiological factors, such as genetic susceptibility, dysfunction of different neurotransmitter systems or environmental, stressogenic and interfamilial influences. Recently, an autoimmune hypothesis has gained acceptance, which proposes that schizophrenia is one of a spectrum of neuropsychiatric diseases in which an autoimmune attack on the brain occurs. It is also possible, however, that the immunological changes seen in schizophrenic patients are secondary to the disease itself. The main evidence supporting an autoimmune hypothesis is the presence of immunological alterations in schizophrenia that also occur in other autoimmune diseases, e.g. an elevation in serum immunoglobulin levels, a decrease in mitogen responses, morphologically abnormal lymphocytes, an increase in antibrain antibodies, an increase in antibodies to nuclear factor, and a decrease in CD4+ T cells. An autoimmune etiology, if proven correct in the pathogenesis of schizophrenia, would have potential implications for the direction of future psychopharmacological therapies. PMID- 7862264 TI - Biochemical findings of negative symptoms in schizophrenia and their putative relevance to pharmacologic treatment. A review. AB - The most prominent biochemical finding in schizophrenic patients with negative symptoms appears to be the reduction in central dopaminergic, serotonergic and noradrenergic activity. This decrease in amine activity tends to be associated with structural brain abnormalities, i.e., cortical atrophy or enlarged ventricles. There are indications that typical neuroleptics reduce those negative symptoms of schizophrenia that are secondary to positive symptoms when these are effectively treated. However, negative symptoms of schizophrenia that occur independently of positive symptoms may also be reduced with monoamine oxidase inhibitors and atypical antipsychotic drugs, such as clozapine. The latter's efficacy seems to be related to their pharmacological profile, i.e., their interference with dopaminergic, noradrenergic and serotonergic receptor systems and metabolism. PMID- 7862265 TI - Salivary testosterone and simple reaction time parameters. AB - A study on 64 healthy young men was carried out to investigate the relationships between salivary testosterone (TS) levels and simple reaction time (RT) parameters under baseline and experimental stress conditions. Two similar simple RT tasks during an anticipation period (test 1, without feedback) and a stress period (test 2, feedback) were used. Electric skin shocks (test 2) were either given contingently to previous performance or noncontingently using a yoked design. Saliva samples obtained during the baseline period were used to split the sample into groups of low and high TS levels according to the median. As expected, lower TS baseline levels were associated with higher mean RT and intraindividual standard deviations. Furthermore, lower TS levels combined with noncontingent feedback resulted in larger numbers of passive avoidance reactions. PMID- 7862266 TI - Effects of thyrotropin- and corticotropin-releasing hormone on blood pressure and plasma catecholamines in the anesthetized rat. AB - The neuropeptides thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH) have been found to be potent stimulators of the autonomic nervous system in both experimental animals and humans. We studied the effects of different doses of CRH and TRH given intracerebroventricularly in the urethane anesthetized rat and a single dose of CRH in the chloral hydrate-anesthetized rat to elucidate the effects of these peptides in the unconscious state. All TRH doses studied enhanced blood pressure and noradrenaline and adrenaline secretion. Surprisingly, there were no blood pressure increases following administration of 0.4, 1.3 and 1.7 nmol CRH. In general, there was a tendency for blood pressure to decrease with the largest drop observed after 1.7 nmol CRH. Our data suggest that only TRH clearly augments blood pressure and catecholamine secretion in the anesthetized animal, while CRH does not exert major effects under the two anesthetic conditions employed. PMID- 7862267 TI - Effects of caffeine on perceptual judgment. AB - The present study examined the effects of caffeine on the estimation of felt width of blocks employing haptic presentation. Following a between-subject design, 160 male postgraduate students classified as high or low impulsives received either placebo or one of four doses of caffeine citrate (1, 2, 3 and 4 mg/kg body weight). A double-blind procedure was adopted for drug administration. Caffeine produced differential effects on the performance of high and low impulsives, facilitated performance (decreased error in perceptual judgment) in high impulsives but had no influence on the performance of low impulsives. The dose-response trends also followed different patterns in the two groups of subjects. PMID- 7862268 TI - Quantitative EEG changes in cocaine withdrawal: evidence for long-term CNS effects. AB - Quantitative EEG changes were studied during cocaine withdrawal in 36 subjects. All subjects had used cocaine orally (n = 28) or intravenously (n = 8) within 48 h of admission to an inpatient unit. EEGs were recorded 2 and 6 days following admission. Nine subjects returned for a 1-month follow-up EEG. Modal EEG frequency significantly decreased on day 6 compared to day 2. The most dramatic change in both absolute and relative power from day 2 to day 6 was a decrease in the beta 2 (18-26 Hz) band. Those subjects who returned for the 4-week follow-up showed a further decrease in beta 2 power. Power in the beta 2 band was significantly greater for the intravenous users than for the smokers, and the decrease in power from day 2 to day 6 was also significantly greater in this group. While acute effects of cocaine on the EEG have been reported to last only several hours, this study indicates that chronic use may cause longer lasting neuroadaptive changes, particularly in those who have used cocaine intravenously. PMID- 7862269 TI - Event-related potential amplitude/intensity slopes predict response to antidepressants. AB - We measured event-related potential (ERP) component amplitudes to four intensities of randomly presented tones. Patients diagnosed with major depressive disorder were tested prior to and following a clinical trial of antidepressant medication. Slope of P2 amplitude as a function of stimulus intensity was calculated for each subject and condition. Subjects were divided into two groups (responders and nonresponders) based on their Hamilton Rating Scale for depression scores following treatment. Responders had significantly larger P2 slopes prior to treatment than did nonresponders. P2 slopes did not differ significantly between responders and nonresponders following antidepressant treatment. These data support the conclusion that P2 amplitude/intensity slope may be a predictor of response to treatment with antidepressant medication. PMID- 7862270 TI - Reliability of transcranial colour-coded real-time sonography in assessment of brain tumours: correlation of ultrasound, computed tomography and biopsy findings. AB - Transcranial colour-coded real-time sonography (TCCS) was carried out in 25 patients with brain tumours to determine whether this noninvasive method provides additional information about the extent of solid tumour, its differentiation from oedema, and its tissue components. All 25 patients had serial computed tomography (CT)-guided stereotactic biopsies. Comparison of ultrasound, CT and histological findings revealed that the vast majority of contrast enhancing areas on CT were hyperechogenic (32/33; 97%) and contained tumour tissue (29/32; 91%). Hyperechogenic areas always represented solid tumour (23/23 patients), even when CT showed low density non-enhancing lesions. In lesions hypoechogenic on TCCS and low density on CT, histology consistently revealed necrotic tumour (7/7). Biopsies obtained from parenchyma with normal echogenicity revealed tumour in only 3 of 16 specimens. Despite the high specificity of TCCS in the differentiation of tumour components, its sensitivity to tumour was inferior to that of CT (24/25; 96%). TCCS thus allows noninvasive preoperative identification of tumour tissue and its extent setting. PMID- 7862271 TI - True proton density and T2-weighted turbo spin-echo sequences for routine MRI of the brain. AB - Our aim was to evaluate the diagnostic reliability of turbo spin-echo (TSE) sequences compared to a conventional dual-echo spin-echo (SE) sequence in routine brain MRI at 1.0 T. The following demands were made on TSE sequences: acquisition time-reduction of at least 50% and true proton density (PD) contrast (low-signal cerebrospinal fluid). A conventional spin-echo and two single-echo TSE sequences were used in 150 patients, a dual-echo TSE sequence in addition in 50 patients. Demonstration of most anatomical structures and disorders was equivalent with TSE and SE sequences. Advantages of TSE were reduced flow artefacts on T2-weighted images, better lesion contrast on PD-weighted TSE images (especially in the dual echo sequence) and acquisition time reduction to about 5 min (single-echo TSE) and 3:35 min (dual-echo TSE). Disadvantages of TSE were: reduced contrast of iron containing substances such as haemosiderin and of areas of calcification. By virtue of the shorter acquisition time and diagnostic reliability dual-echo TSE proved the best sequence. If it is used with only one acquisition--whereby image quality but not diagnostic reliability is slightly decreased--acquisition time can be further reduced to 1:48 min. Application of a susceptibility-sensitive gradient-echo sequence, such as FLASH, compensates for the disadvantages mentioned above. PMID- 7862272 TI - The value of three-dimensional turbo-FLASH and spin-echo sequences in the detection of pituitary microadenomas following gadolinium administration. AB - Our purpose was the comparison of T1-weighted spin-echo (SE) and three dimensional (3D) Turbo-fast low-angle shot (FLASH) (3DTFL) in detection of 14 pituitary microadenomas following intravenous gadolinium (Gd). 3DTFL represents an important improvement in the diagnosis of pituitary microadenomas. In two cases, the site of the tumour was correctly identified only by Gd-enhanced Turbo FLASH. Nevertheless, in two other cases, the Gd-enhanced 3DTFL gave false negative (FN) results while the T1-weighted SE images enabled correct localisation. Replacement of T1-weighted SE by 3DTFL cannot therefore be advocated and use of both contrast-enhanced sequences offers the highest detection capability for microadenomas. PMID- 7862273 TI - CT angiography of the common carotid artery bifurcation: comparison between two techniques and conventional angiography. AB - We prospectively compared CT angiography (CTA) of the common carotid artery bifurcation using two different techniques with conventional angiography in patients with suspected stenoses of the internal carotid arteries in 20 symptomatic patients. Ten patients (Group 1) received 60 cc of contrast (medium 2 cc/sec) and CTA was acquired using 5 mm slices, reconstructed at 3 mm slice thickness. Ten patients (Group 2) received 90 cc of contrast (medium 3 cc/sec) and CTA was acquired using 3 mm slices reconstructed at 1 mm slice thickness. All CTA studies were postprocessed using maximum intensity projection algorithm. Stenoses were graded prospectively from CT angiograms and compared with selective conventional catheter angiograms. In Group 1, CTA overestimated the degree of narrowing in 9 of 10 stenoses proven by conventional angiograms. We interpreted 2 nearly occluded internal carotid arteries, 2 with moderate and marked stenoses, and 2 with no narrowings, but fibromuscular dysplasia on conventional angiograms as occluded on CTA, and 3 vessels as showing marked stenoses, not confirmed by angiography. CTA clearly depicted 1 mild stenosis, 4 normal bifurcations, and 6 occluded internal carotid arteries. In Group 2, CTA overestimated two stenoses; a correct diagnosis was made in 7 normal bifurcations, 3 mild, 2 moderate and 2 severe stenoses, 2 near occlusions, and 2 occlusions. Ulcerations were missed by CTA regardless of the technique utilized. PMID- 7862274 TI - Changes in the basal ganglia and thalamus following reperfusion after complete cerebral ischaemia. AB - We report specific changes bilaterally in the basal ganglia and thalamus following reperfusion after complete cerebral ischaemia. A 69-year-old man, resuscitated after cardiac arrest, showed symmetrical low-density lesions in the head of the caudate nucleus and lentiform nucleus on CT. MRI revealed methaemoglobin derived from minor haemorrhage in the basal ganglia and thalamus, not evident on CT. We suggest that this haemorrhage results from diapedesis of red blood cells through the damaged capillary endothelium following reperfusion. PMID- 7862275 TI - Stenotic kinking of the cavernous internal carotid artery with a giant intra cavernous aneurysm: case report. AB - We report a giant aneurysm of the cavernous internal carotid artery with proximal internal carotid stenosis. The stenosis showed two typical features: a kink at the stenosis and location at the exit from the carotid canal. We believe that the cavernous portion of the internal carotid artery is compressed medially by the giant aneurysm and a kink occurs at the point where the artery leaves the bony carotid canal. PMID- 7862276 TI - Bilateral aneurysms of the cavernous internal carotid arteries following yttrium 90 implantation. AB - We present a case of bilateral aneurysms of the cavernous internal carotid arteries probably caused by radiation damage due to yttrium-90 implantation for a pituitary adenoma. Other possible aetiological factors are discussed. PMID- 7862277 TI - Oculomotor nerve palsy due to thrombosis of a posterior communicating artery aneurysm following diagnostic angiography. AB - We present a patient who developed a painful third nerve galsy two days after angiography had demonstrated a large aneurysm on the P1 segment of the left posterior cerebral artery. CT at this stage demonstrated extensive thrombus within the previously uncomplicated aneurysm. The haemodynamics of this aneurysm resulted in incomplete clearance of contrast medium from its fundus and we posit that this may have promoted thrombus formation. Six months later the aneurysm was shown angiographically to be completely occluded. PMID- 7862278 TI - Dural arteriovenous fistula in the falx cerebri. AB - The case of a 73-year-old patient with a pure dural arteriovenous fistula within the falx cerebri, first manifested as subarachnoid and intraventricular haemorrhage is reported. There was no positive history for both the congenital and the acquired type of lesion. Computed tomographic findings and the relatively unusual angiographic features are discussed. PMID- 7862279 TI - Dural arteriovenous fistula of the inferior petrosal sinus producing contralateral exophthalmus. PMID- 7862280 TI - Patterns of skull base fracture: a three-dimensional computed tomographic study. AB - Three-dimensional (3D) computed tomographic (CT) reconstructions were studied retrospectively in 14 patients with skull base fractures. Our aim was to assess the clarity of visualisation and pattern of these fractures. The reformations were obtained from 3 mm thick two-dimensional (2D) CT images. The 2D data stored on optical discs were retrieved and reformatted using the scanner's software. The 3D technique could demonstrate the presence of fractures as well as 2D images. It was of special value in defining the depth and extent of fractures in the floor of the cranial fossae. Undisplaced and displaced fractures could both be demonstrated. Fractures in the anterior fossa run diagonally towards the midline and then cross the cribriform plate of the ethmoid bone. Fractures of the middle fossa run obliquely anteroposterior. Fractures in the lamina papyracea and cribriform plate were difficult to reconstruct due to the thinness of these bones and threshold definitions. The volume of the 3D block determines the angles suitable for viewing the fractures. In spite of present technical difficulties, the 3D images are of greater anatomical and diagnostic value, particularly in anterior fossa fractures. There is no additional radiation risk to the patient, since reconstructions are made from routine 2D images. PMID- 7862281 TI - Postmortem MRI of the spinal cord in multiple sclerosis. AB - Postmortem magnetic resonance imaging (MRI) of the spinal cord and the brainstem in a patient with multiple sclerosis are compared with the histopathological findings. Abnormal high signal intensity areas on T2-weighted images correspond precisely to demyelinated areas. PMID- 7862282 TI - Spinal cord sarcoidosis. AB - We present a case of spinal cord sarcoidosis which resembled a disseminated intramedullary tumour. The case is unusual because the spinal cord is only rarely affected by sarcoidosis and the patient developed a neurological deficit as the first manifestation of the disease. This condition thus has to be considered in the differential diagnosis of primary intramedullary tumours, or metastatic disease with involvement of the spinal cord. PMID- 7862283 TI - Plaque-like meningioma involving the temporal bone, sinonasal cavities and both parapharyngeal spaces: CT and MRI. PMID- 7862284 TI - Petrous apex mucocele: high resolution CT. AB - Mucocele of the petrous apex is very rare, only three cases having been reported. Since this area is inaccessible to direct examination, imaging, preferably high resolution computed tomography (HR CT) is essential. We report a case showing an eroding, non enhancing mass with sharp, lobulated contours, within the petrous apex. The presence of a large air cell on the opposite side suggested a mucocele. PMID- 7862285 TI - Experimental study and clinical use of poly(vinyl acetate) emulsion as liquid embolisation material. AB - A new material, an emulsion of poly(vinyl acetate) was experimentally developed and clinically used to overcome several disadvantages in currently used liquid embolisation materials. The emulsion microparticles, 0.3-0.7 microns in size, possessed cationic charge on the surface and hence aggregated immediately on contact with fluids containing anions. This inert polymer has the advantage that it does not induce a deleterious reaction in living tissue. Moreover, its medium is water and it is not adhesive, like the cyanoacrylates. Several concentrations of emulsion were injected into the renal arteries of dogs. For the investigation of tissue reactions and the possibility of recanalisation, the emulsion was injected into rats both subcutaneously and into the renal arteries. The renal artery injections in dogs showed adequate radiopacity and consistent complete occlusion. The lower the concentration of the emulsion, the smaller the arteries which could be occluded. Even at very low concentrations, however, venous occlusion did not occur. Histological study of the embolised rat kidney revealed no detectable damage in the vessel wall and no recanalisation for up to 6 months. The subcutaneously injected PVAc emulsion elicited mononuclear cell infiltration and gradual centripetal fibrosis, without any deleterious effect on the surrounding tissue. A cerebral arteriovenous malformation (AVM) was embolised using the material. Histology of the resected nidus showed findings similar to those in the animal experiments. PMID- 7862286 TI - Management of midbrain cyst with repeated CT guided aspiration. PMID- 7862287 TI - MRI of the normal brain from early childhood to middle age. I. Appearances on T2- and proton density-weighted images and occurrence of incidental high-signal foci. AB - The magnetic resonance images of 67 healthy subjects aged 4-50 years were studied for differences in general signal intensity between the different brain structures, the frequency of focal intensity changes in the brain, and variations in size of the cerebrospinal fluid (CSF) spaces. In adults over 25 years of age the thalamus gave lower signal than the putamen or caudate nucleus. Definite periventricular high signal was found in the white matter of one third of subjects of all ages. Small (< 5 mm in diameter) high signal foci were found in the cerebral white matter on T2-weighted images in 27% of subjects (20% of healthy children and adolescents and 34% of adults). They gave high signal on both short and long echoes in 11% of children and adolescents and in 22% of adults; 51% of all foci gave high signal with both echoes. This does not support the hypothesis that they are caused mainly by enlarged Virchow-Robin spaces. Of the high signal foci on T2-weighted images, 86% were in watershead areas. Two foci were found in one subject in the periventricular watershed area (beside the tips of the frontal horns) and they were never seen in the other deep white matter regions. In healthy, relatively young subjects with no known risk factors, high signal foci other than Virchow-Robin spaces, were common; neither their prevalence nor their number correlated with age in this series. A few slightly large sulci were found in some adults. PMID- 7862288 TI - MRI of the normal brain from early childhood to middle age. II. Age dependence of signal intensity changes on T2-weighted images. AB - We examined 66 healthy volunteers aged 4 to 50 years by magnetic resonance imaging (MRI) and the signal intensity was measured on T2-weighted images in numerous sites and correlated with age and sex. Using distilled water and cerebrospinal fluid (CSF) as references on each slice, we calculated the signal intensities of the brain structures. Calculated ratios between structures did not change with age, except for those of the globus pallidus and thalamus, in which the signal intensities decreased more rapidly. The signal intensities of other brain structures changed equally but this could not be discerned visually and quantitative measurements were required. The signal intensities in the white and deep grey matter decreased rapidly in the first decade and then gradually to reach a plateau after the age of 18 years. Maturation of the brain thus seems to continue until near the end of the second decade of life. No sex differences were found. Quantitative analysis requires intensity references. The CSF in the tips of the frontal horns seems to be as reliable as an external fluid reference for intensity, and can be used in routine examinations provided the frontal horns are large enough to avoid partial volume effect. PMID- 7862289 TI - Late cranial MRI after cranial irradiation in survivors of childhood cancer. AB - We carried out MRI on 43 survivors of childhood cancer after different treatment protocols with or without cranial radiotherapy. They were free of disease, therapy having been discontinued 2-20 years earlier. Treatment had been for various malignancies, excluding brain tumours; 27 had received cranial irradiation for acute lymphoblastic leukaemia (ALL) or lymphoma. Two asymptomatic young women treated for ALL had falx meningiomas. White matter changes, low intensity foci (representing calcification or old haemorrhage) and heterogeneous intensity focic old haemorrhages) were seen only in patients who had undergone radiotherapy. Because of the possibility of benign, potentially curable brain tumours occurring after cranial irradiation, it may be wise to carry out occasional cranial imaging in the follow-up of these patients. No routine imaging follow-up is needed after chemotherapy alone. PMID- 7862290 TI - Outcomes assessment: choosing a psychometrically sound nursing achievement test. AB - Summative assessment of nursing education is a common pre-graduation activity. The author describes how nursing faculty members can ensure that they have chosen a psychometrically sound nursing achievement test. First, the criteria by which standardized examinations should be evaluated are explored. Then, two common achievement tests, the Mosby Assess Test and the National League for Nursing Diagnostic Readiness Test for RN Licensure, are analyzed for their strengths and limitations. PMID- 7862291 TI - Critiquing as a method of evaluation in the classroom. AB - The criticism model of evaluation in a humanistic educative paradigm is a shared teacher/student evaluative activity based on a trusting relationship in which students become connoisseur critics. Among the standards for critiquing are criteria for student/teacher interactions and criteria for learning activities. The author provides examples of student/teacher critiquing activities employed in a graduate nursing course and suggests ways for faculty to develop skills in the critique method of evaluation. PMID- 7862292 TI - Accidental needlestick injuries in the academic setting: a model follow-up program. AB - Developed in response to needlestick injuries received by university nursing students, a model for initiating a comprehensive faculty and student follow-up treatment program for incidents involving blood and body fluids is presented. Providing an overview of need and risks, the authors review the program components, such as reporting mechanisms, program initiation, use of screening tests, recommended treatment modalities, and a decision-analysis for guiding the process. PMID- 7862293 TI - Tribal education: reflections from the Pine Ridge Indian Reservation. AB - Attracting and retaining Native American students in tribal nursing programs is crucial to the health and well-being of Native American populations. The authors share their experiences teaching nursing in the associate degree program at the Oglala Lakota College on the Pine Ride Reservation in South Dakota. The authors communicate the importance of the work of tribal nursing programs and illustrate the experience as an opportunity for nurses who are interested in cross-cultural development. PMID- 7862294 TI - Peer mentoring for reflective teaching: a model for nurses who teach. AB - Given the variety of forums and audiences that post-baccalaureate and masters prepared nurses address, nurse educators need to introduce students to models for developing teaching expertise over the course of their professional lives. The authors introduce such a framework, called Peer Mentoring for Reflective Teaching. The framework enhances teaching skills through consultation with peer mentors to help nurses design relevant learning experiences and reflect on the planning and presentation of teaching episodes. PMID- 7862295 TI - The personal problem-solving side of the nursing process. PMID- 7862296 TI - Rural health initiatives: opportunities for nursing education and practice. PMID- 7862297 TI - Case management experience helps RN students incorporate professional role attributes. PMID- 7862298 TI - Successful catheterization of a female patient. PMID- 7862299 TI - Extended shifts for nursing students? PMID- 7862300 TI - The use of a transition clinical conference to reduce student anxiety at new clinical sites. PMID- 7862301 TI - Promoting acquisition of telecommunications skills. PMID- 7862302 TI - Why can't new grads think like nurses? PMID- 7862303 TI - Anonymous grading: an ethical teaching strategy. AB - Increasing emphasis on student rights, as well as attention to ethics, has focused awareness on strategies that faculty can implement to ensure that the subject of ethics is illustrated in classroom teaching. The author discusses anonymous grading as one strategy to operationalize ethics in the classroom. As an ethical concept, justice is a primary concern in the implementation of impartial and fair evaluation of students' work. PMID- 7862304 TI - Men in nursing: an historical perspective. PMID- 7862305 TI - LPN-to-BSN: an accelerated program. PMID- 7862306 TI - Revising death education. AB - Current nursing education approaches toward death and dying are outdated and need revision. Inadequate preparation in this critical area causes problems for students after they graduate. Practicing nurses report they are unprepared academically to cope with the stresses of working with dying clients and their families. The author reviews the role of formalized death education programs for students in lowering personal anxiety and discomfort while teaching skillful interventions for professional practice. PMID- 7862307 TI - Planning for study abroad. AB - There is more to planning for study abroad than buying airplane tickets. Providing a successful course away from the host institution requires a great deal of planning by the educator. This planning includes course development, budget, marketing, travel, housing, food, and entertainment. Careful preparation provides both the educator and student a unique and enriching experience that goes beyond the traditional course. PMID- 7862308 TI - Nursing visions: the nurse as manager of patient care. PMID- 7862309 TI - Teaching nursing theory through an election campaign framework. AB - The author describes a teaching-learning strategy that helped students gain an enhanced appreciation for nursing theories and their application to nursing practice. Students selected, campaigned for, and elected a nursing theorist to serve as Vice President for a Nursing Theory Club. Through the campaign and election process, they were able to select and investigate a nursing theorist and apply the theorists' work to nursing practice. Campaign materials, campaign headquarter displays, and campaign speeches allowed for assessment of many program outcomes including effective written and verbal communication, critical thinking, professionalism, empiric knowledge, and aesthetics. PMID- 7862310 TI - Noncognitive factors that put students at academic risk in nursing programs. AB - A random sample of 112 baccalaureate nursing students were surveyed. The relationship of noncognitive variables to student academic success was identified. Findings suggest that 1) students who do not understand how to negotiate the system, or students who feel they will not "fit in" may have difficulty, 2) male students are more likely to need support for their academic plans, and 3) minority students may need support to establish community ties. PMID- 7862311 TI - Free writing assignments. PMID- 7862312 TI - Male nursing students' perceptions of clinical experience. AB - Christman questions the paucity of research completed with male nurses, given their history in the profession, and challenges nurse researchers to study in this area. To address this need, a phenomenologic study was undertaken to examine the perceptions of clinical experience of nine male nursing students. Findings revealed that men perceive a need to develop cognitive, psychomotor, caring, and intuitive skills. They want to be valued members of the team. The importance of assessing and reassessing role-related boundaries and the need to deal with their feelings about being men in settings that traditionally value women as primary care givers for intimate bodily functions are important. The results of this study offer important insights into male student nurses' clinical experiences that can be useful for other male nursing students as well as nursing educators. PMID- 7862313 TI - Addressing the academic progression of students encountering mental health problems. AB - Contending with the academic progression of baccalaureate nursing students who are encountering mental health problems is not an easy task for educators. The authors have delineated a protocol of action for dealing with such problems and have applied the protocol to a hypothetical case study. Examples of related correspondence with the student are included. PMID- 7862314 TI - The Houston Linkage Model 1992; an update. AB - The authors provide an update on the development of an innovative model to promote faculty practice. Since its inception, the model has become more sophisticated and has more than tripled its revenues to the school of nursing. Faculty practice is an integral part of the teaching programs and has been the impetus for increased research productivity among faculty members. The authors discuss model changes, including the management of revenues and decentralized control of funds. PMID- 7862315 TI - Learning among ethnically diverse nursing students and faculty. PMID- 7862316 TI - Creative strategies for teaching nursing research. PMID- 7862317 TI - Lecture presentations using varied points of reference. PMID- 7862318 TI - Promoting health through fun and games. PMID- 7862319 TI - Outpatient clinics as clinical sites. PMID- 7862320 TI - A guide for care planning. PMID- 7862321 TI - Variations in teaching and practices of blood pressure measurement. PMID- 7862322 TI - Increased mentoring necessary to ensure safe medication delivery. PMID- 7862323 TI - Student papers: should they publish or perish? PMID- 7862324 TI - Healthcare reform: from public policy vision to professional personal action. PMID- 7862325 TI - SNA news: a newsletter written by and for student nurses. PMID- 7862326 TI - Academic freedom: history, constraints, and recommendations for nursing education. AB - Nurse faculty members may have a limited awareness of the rights and responsibilities inherent in academic freedom. The author explores the development of academic freedom and those practices in nursing education that have limited nurse educators' academic freedom. Rights and responsibilities of and for faculty and students and constraints to academic freedom are examined. The article closes with recommendations that will help ensure increased awareness of and adherence to the rights and responsibilities of academic freedom. PMID- 7862327 TI - NINE: newspapers in nursing education. AB - Newspapers in education are not new, but the use of newspapers in nursing education (NINE) is just being initiated, because of the recognition that few students are informed about world events. The use of newspapers in the classroom can foster nurse leaders who are well informed and have appropriate communication skills (reading, writing, critical thinking) that prepare them for lifelong learning. The author describes the development and implementation of the newspaper approach in nursing education, based on Knowles' theory of adult learning. Outcomes of this approach are reported. PMID- 7862328 TI - Effects of mind mapping on student achievement in a nursing research course. AB - Nurse educators face the problem of getting students to understand massive amounts of content and see relationships between concepts. The author addresses this problem by comparing the effectiveness of one technique, mind mapping, to more traditional approaches. In addition, creative teaching strategies such as mind mapping can make a class not only more interesting, but fun. PMID- 7862329 TI - Evaluation of a comprehensive advisement program designed to enhance student retention. AB - Nursing schools are experiencing an increase in enrollment. However, students are done a disservice when there are no strategies to retain them. A primary strategy for enhancing student retention is the implementation of an effective advisement program. The authors describe the implementation and evaluation of a comprehensive advisement system that was a major component of a special project grant from the division of nursing designed to enhance student retention. PMID- 7862330 TI - Education about death, dying, and bereavement in nursing programs. AB - The authors report the results of a March 1992 survey of 650 baccalaureate nursing education programs concerning the education that they provide in the area of death, dying, and bereavement. The survey inquired about death education content in the curriculum, theoretic models, and whether organ/tissue donation is addressed. Results indicate that many schools are using outdated models. The authors suggest ways to address these issues more adequately. PMID- 7862331 TI - Accommodating nursing students' diverse learning styles. AB - The authors present a framework for understanding diverse learning style/cognitive-style models and assessment instruments, review the literature on learning styles in general and the Dunn and Dunn Model specifically, and identify research areas for nursing educators. The authors challenge previous research with nurses and nursing students that focused on group, rather than individual interventions. They also explain why instruments that focus on only one or two constructs on a bipolar continuum, rather than on multiple learning-style constructs, restrict the possibility of revealing positive outcomes. PMID- 7862333 TI - Alleviating the mechanics of paper writing. PMID- 7862332 TI - Senior-led freshman groups: a strategy for professional development. AB - Faculty members are challenged to promote professional nurse development in undergraduate students. The authors discuss an experimental teaching/learning strategy for senior nursing students and groups of freshman students in a baccalaureate nursing program. This strategy provided a unique opportunity for professional role socialization and school integration in first-year students and increased competence in teaching skills and confidence as professional role models in the seniors. Based on evaluations by the participants, the experimental teaching strategy was a positive experience for both freshman and senior students. PMID- 7862334 TI - Role playing the historical perspective of nursing. PMID- 7862335 TI - Faculty support for preceptor nurses. PMID- 7862336 TI - Track student progress with a database. PMID- 7862337 TI - A manual for test construction. PMID- 7862338 TI - Clinical memos: a tool for continuity in learning. PMID- 7862339 TI - A strategy for estimating blood loss. PMID- 7862340 TI - Critical thinking. PMID- 7862341 TI - Household transmission of HIV infection. PMID- 7862342 TI - Nursing information systems for nurse practitioners. PMID- 7862343 TI - Sexual activity in the young female adolescent. PMID- 7862344 TI - Recognizing nasal vestibulitis in the primary care setting. PMID- 7862345 TI - Nurse practitioners: the early years (1965-1974) PMID- 7862346 TI - Primary care approach to lymphadenopathy. AB - Lymphadenopathy is a common presenting symptom. It is a manifestation of many disease processes ranging from self-limiting ones to those that are incurable and fatal. The diagnostic factors used to evaluate the etiology of one or more enlarged lymph nodes include: the age of the patient, the clinical history, the physical examination, and the anatomic location/nodal history and characteristics. With the selection of the proper tests, unnecessary or invasive treatments can be avoided. Ultimately, when a neoplastic process is suspected, a lymph node biopsy is the definitive test. PMID- 7862347 TI - Management strategies for hormonal replacement therapy. AB - Every year for the next 10 years, approximately 4 million women will become perimenopausal. For these women an important decision is whether or not to use hormone replacement therapy (HRT), and if they decide affirmatively, then, for how long to use it. The health provider must be able to help the woman in her decision making process by identifying the risks, benefits, and contraindications to this therapy. This information, based on the latest research, is presented in this article along with the types of hormones available, prescription regimens, side effects, management issues, and possible alternatives to hormone therapy. PMID- 7862348 TI - Management of the uncomplicated pregnant diabetic client in the ambulatory setting. AB - This article discusses health care provider management of the uncomplicated pregnant diabetic client in the ambulatory setting. The primary care management process includes combining knowledge about the individual with knowledge of the disease process of diabetes in order to identify problems. Through a sharing of knowledge and information and a team approach, health care providers and their clients work together to develop and implement a logical sequence of safe, comprehensive care. The purpose of this article is to provide information on health care management of uncomplicated diabetes in pregnancy in the ambulatory setting. Topics include classifications of diabetes, normal insulin metabolism and insulin metabolism during pregnancy, implications of diabetes for the mother and fetus, preconception management and risk factor identification, screening and diagnostic tests, and management. Management includes baseline assessment, blood glucose monitoring, nutrition, exercise and insulin therapy as well as fetal surveillance and postpartum follow-up. PMID- 7862349 TI - Papanicolaou smear. PMID- 7862350 TI - Rehabilitation services in the health sector: the perspectives of providers and consumers: Part 1. AB - AIMS: To establish the degree of implementation of the Strategic Planning Guidelines for Area Health Boards--Services for Adults with Physical Disability, published by the Department of Health in 1989, the services being provided, and the priorities for future service provision. METHODS: Two postal surveys of area health boards (AHB's) were carried out in 1991. The first asked about the terminology of rehabilitation, administrative structure, advocacy, service audit, inventory of services, regional service delivery, and consultation processes. The second asked about the rehabilitation services provided, the type of disability of the consumers of the service, the reasons why services were or were not provided, the service gaps that existed, and the priorities that existed to fill those service gaps. RESULTS: The major finding was that while all area health boards adopted the rehabilitation concepts in principle, service development was impeded in many cases by the failure to provide resources to plan and develop the service. Some were providing comprehensive services. Most AHB's provided services for people with physical or multiple disabilities. All provided statutory services such as district nursing and home help, while most provided regular medical reviews, physiotherapy, occupational therapy, speech therapy, etc. Only about half provided attendant care, driving assessment, and swimming for people with disabilities, while less than half supported disability information services (DIS). Attendant care was seen as high priority to fill gaps in service, but was seen as the funding responsibility of the Department of Social Welfare. CONCLUSIONS: Service provision reflected a traditional approach to the provision of rehabilitation services. The development of innovative service delivery will require crown health enterprises to reevaluate their present level of commitment to rehabilitation services and to assess the effectiveness of reallocating some funds from acute services into rehabilitation. PMID- 7862351 TI - Stevens-Johnson syndrome associated with erythromycin therapy. PMID- 7862352 TI - Brunner's gland adenoma: case report. PMID- 7862353 TI - Sir James Elliott, medical journalist supreme. AB - James Sands Elliott was editor of the New Zealand Medical Journal from 1911 to 1933. He was a powerful writer in a flamboyant style, erudite and filled with classical and literary allusions and quotations. We are told that doctors of the time, on receiving their journals, would turn first to the editorial to see "what JSE has got to say." He served the profession in numerous ways, as chairman of council and president of the New Zealand Branch of the British Medical Association (BMA), as president from 1929 to 1955 of the New Zealand Branch of the British Empire Cancer Campaign (now the Cancer Society), and as a member of the Medical Council, the Board of Health and the Medical Research Council. It was his outstanding ability as a medical journalist, however, which made him one of the most powerful figures in New Zealand medicine in his time. He ardently upheld worthy causes in the interests of the medical profession as he saw them and wrote trenchant editorials on those subjects. PMID- 7862354 TI - Health research in the Pacific: in search of a reality. PMID- 7862355 TI - Randomised trial of chelation therapy. PMID- 7862356 TI - Hepatitis C from needlestick injury. PMID- 7862357 TI - Tuberculosis in children. PMID- 7862358 TI - 5 Fluorouracil cardiotoxicity. PMID- 7862359 TI - Emergency equipment in doctor's surgeries. PMID- 7862360 TI - Female sterilisation by the vaginal route. PMID- 7862361 TI - Hepatitis B carrier follow up. PMID- 7862362 TI - Medication and flying. PMID- 7862363 TI - The safety, tolerability and efficacy of transdermal nicotine (Nicotinell TTS) in initially hospitalised patients. AB - AIM: We studied a transdermal nicotine system with minimal behavioural intervention in hospitalised patients to assess patient acceptability, safety and efficacy. METHOD: In an open noncomparative study, 80 smoking patients (42 men and 38 women) were enrolled. They received 24-hour nicotine patches and simple support for 12 weeks and were followed for up to 26 weeks. Smoking was assessed by interview, expired air carbon monoxide and blood cotinine. RESULTS: Side effects included itch and local erythema (4), insomnia (7), abnormal taste (3). Two subjects withdrew from the study because of side effects. At 12 weeks 17 were nonsmokers. At 26 weeks 19 of 80 were nonsmokers and a further 14 had reduced their intake significantly. CONCLUSIONS: The nicotine skin patch proved to be safe and well tolerated. Efficacy was comparable to controlled trials of transdermal nicotine patches. PMID- 7862364 TI - Percutaneous renal biopsy: an audit of a 2 year experience with the Biopty gun. AB - AIM: To review and audit our experience in the use of the semiautomated spring loaded Biopty gun with ultrasound guidance for renal biopsy, and the results with those obtained eleven years earlier using the Franklin-modified Vim Silverman needle. METHOD: We reviewed retrospectively the hospital notes of all patients who under went a percutaneous renal biopsy over a 2 year period at Christchurch Hospital. RESULTS: There were 126 renal biopsies in 117 patients. Proteinuria (32%) remained the most common indication for renal biopsy. Renal transplant dysfunction (21%) was the next most common indication. IgA nephropathy was more frequently diagnosed than 11 years previously. Despite the use of a finer (18 gauge versus 14 gauge) needle, specimen adequacy was not jeopardised. Bleeding complications (7.9%) are still a significant occurrence with the Biopty gun. Complications in nine of the 10 cases developed within 8 hours of the biopsy. CONCLUSIONS: Over 50% of the renal biopsies were performed for the investigation of proteinuria or renal transplant dysfunction. The semiautomated spring-loaded Biopty gun with ultrasound guidance is easily used by the one operator but, in our experience, was not associated with a lower complication rate than the 14 gauge Vim Silverman needle. We now perform the elective percutaneous renal biopsy as a day case. PMID- 7862365 TI - Battering in pregnancy: an assessment of two screening methods. AB - OBJECTIVE: To compare two different screening techniques for identifying women with a history of domestic violence or battering in the current pregnancy. METHODS: The five-question Abuse Assessment Screen was incorporated into routine social service interviews and applied prospectively to all registrants for routine prenatal care at Women & Infants' Hospital during an initial social service evaluation from September 7 through October 29, 1993. This group (N = 143) was compared to a historical control group of all new registrants from July 12 through September 3, 1993 (N = 191) who had routine interviews by social services. Demographic and medical data were compared, as well as the specific information addressed by the screen, including history of domestic violence, physical or sexual violence within the last year, violence during the current pregnancy, recent sexual abuse, and fear of partner. RESULTS: The median age of the study population was 23 years old, 50% were white, 63% were single, and 42% had no insurance. There was a higher detection of violence in all categories using the Abuse Assessment Screen compared with the standard interview--any history: 41 versus 14% (relative risk [RR] 3.0, 95% confidence interval [CI] 2.0 4.5); recent history: 15 versus 3% (RR 5.6, CI 2.2-14.5); during pregnancy: 10 versus 1% (RR 9.3, CI 2.2-40.5); recent sexual abuse: 4 versus 0% (P = .006); and fear of abuser: 6 versus 3% (RR 1.8, CI 0.6-5.0). CONCLUSION: Use of a structured screen improves detection rates of battering both before and during pregnancy, enabling clinicians to have a greater opportunity to intervene. PMID- 7862366 TI - Using incentives to increase participation in prenatal care. AB - OBJECTIVE: To test the effectiveness of offering two kinds of incentives to encourage low-income women's participation in prenatal and postpartum care. METHODS: Two hundred five Medicaid-eligible women enrolled in a prenatal clinic were randomly assigned to receive a $5.00 gift certificate (N = 51) or a gift certificate and a chance to win a $100 raffle (N = 53) for each prenatal appointment they kept. Controls (N = 101) and the two experimental groups were interviewed postpartum about their satisfaction with prenatal care. Women in the three groups were compared for the number of prenatal and the postpartum appointments, satisfaction with care, length of gestation, and birth weight. RESULTS: Thirty-nine percent missed one to seven prenatal appointments, and 45% missed the postpartum appointment. There were no significant differences among the three groups in any of the outcome variables. Women missed appointments because of the lack of transportation, poor weather, and illness. CONCLUSION: Providing incentives does not overcome barriers to receiving prenatal care. PMID- 7862367 TI - Urban rape survivors: characteristics and prevalence of human immunodeficiency virus and other sexually transmitted infections. Multicenter Crack Cocaine and HIV Infection Study Team. AB - OBJECTIVE: To determine the prevalence of recent rape, the characteristics or recent rape survivors, and the seroprevalence of human immunodeficiency virus (HIV), syphilis, and genital herpes (HSV-2) among recent rape survivors. METHODS: We surveyed women 18-29 years old who were recruited from places unassociated with medical or drug treatment or the criminal justice system in three urban communities where illicit drug use is common. We compared characteristics and HIV, syphilis, and HSV-2 seroprevalence of women who reported recent rape with those of women who denied recent rape. RESULTS: One hundred fifty-one of 1104 (13.7%) women reported having been raped in the year before our interview. Rape survivors were more likely than women who denied recent rape to smoke crack cocaine (86.8 versus 56.7%; odds ratio [OR] 5.0, 95% confidence interval [CI] 3.2 7.8), to be homeless (17.2 versus 6.1%; OR 3.2, CI 2.0-5.2), to report a recent sexually transmitted disease (38.7 versus 18.7%; OR 2.7, CI 1.9-3.9), and to be infected with syphilis (42.4 versus 28.4%; OR 1.9, CI 1.3-2.6) and HSV-2 (71.9 versus 57.5%; OR 1.9, CI 1.3-2.8). Survivors were more likely to acknowledge any HIV risk behavior (including sex work) (85.4 versus 49.5%; OR 5.9, CI 3.9-9.0) and to be HIV-infected (23.3 versus 13.4%; OR 1.9, CI 1.3-2.9). Rape was not independently associated with HIV (OR 0.8, 95% CI 0.4-1.3), syphilis (OR 0.9, 95% CI 0.6-1.3), or HSV-2 (OR 1.3, 95% CI 0.9-2.0) infections after adjustment for confounding factors. CONCLUSION: One in seven women reported being raped recently. Rape was most common among sex workers, crack smokers, and the homeless. Most survivors reported HIV risk behaviors, and many were HIV-infected. Programs to prevent repeated rape, voluntary HIV counseling and testing, and other medical and social services may benefit survivors in these and similar communities. PMID- 7862368 TI - A polymerase chain reaction-enzyme-linked immunosorbent assay method for detecting human papillomavirus in cervical carcinomas and high-grade cervical cancer precursors. AB - OBJECTIVE: To develop and evaluate a novel polymerase chain reaction (PCR)-enzyme linked immunosorbent assay (ELISA)-based method for detecting high-oncogenic-risk human papillomaviruses (HPV). METHODS: An HPV assay based on PCR amplification of a region of the E6 open reading frame and ELISA detection of PCR products that specifically identify high-oncogenic-risk HPV types (eg, types 16, 18, 31, 33, 35, 39, 45, 56, 58, and 65) was developed. Dacron swabs were used to obtain samples from the cervices of 371 women referred for colposcopy. The swabs were analyzed using the PCR-ELISA method. The results of HPV DNA testing were then compared with the results of a repeat Papanicolaou smear and cervical biopsy obtained at the same visit. RESULTS: The sensitivity of the PCR-ELISA HPV test for detecting invasive cervical cancer or high-grade squamous intraepithelial lesions (SIL) was 90%. High-oncogenic-risk HPVs were detected in six of seven women with biopsy-confirmed invasive cervical cancer, 74 of 81 women with biopsy confirmed high-grade SIL, 58 of 128 women with biopsy-confirmed low-grade SIL, and 46 of 155 women with no evidence of cervical disease by colposcopy and cervical biopsy. When used in conjunction with a repeat Papanicolaou test, 97% of the women with invasive cervical carcinoma and high-grade SIL lesions were identified. CONCLUSION: The PCR-ELISA-based HPV detection provides the potential for an automated, rapid, and sensitive test for cervical cancer and high-grade cervical lesions. PMID- 7862369 TI - Does perioperative blood transfusion affect survival in patients with cervical cancer treated with radical hysterectomy? AB - OBJECTIVE: To determine if blood transfusions during or after radical hysterectomy adversely affect survival in patients with invasive cervical carcinoma. METHODS: Two hundred eighty-three women with stage IA2-IIA cervical cancer were treated with radical hysterectomy and pelvic lymphadenectomy from 1980-1989. Thirteen were lost to follow-up, and five others received adjuvant chemotherapy. Among the remaining 265 patients, 131 were given blood transfusions during surgery or within 30 days, whereas 134 were not. The clinical and pathologic characteristics of these two groups were reviewed and analyzed statistically. RESULTS: Transfused and nontransfused patients did not differ with respect to mean age (45.0 versus 43.4 years, respectively), stage, grade, cell type, depth of invasion, or prevalence of nodal metastasis. Transfused patients more frequently received adjuvant pelvic irradiation than did nontransfused (47 versus 33%, respectively, chi 2 P < .05). After a mean follow-up of 51 months (range 13-125), 19 women (14%) in each group were diagnosed as having recurrent disease, predominantly in the pelvis. Using life-table analysis, the calculated 5 year survival was 86% for transfused and 84% for nontransfused patients, a nonsignificant difference. Disease-free survival was also similar. In the study population, grade, depth of invasion, and nodal status predicted survival. When patients were stratified according to age, cell type, stage, depth of invasion, nodal involvement, and use of adjuvant radiation, blood transfusion still did not adversely influence survival. Using the Cox proportional hazards model, only nodal status was an independent predictor of death. CONCLUSION: Perioperative blood transfusion does not impact overall survival or time to recurrence after radical hysterectomy. PMID- 7862370 TI - Combining vaginal ultrasonography and office endometrial sampling in the diagnosis of endometrial disease in postmenopausal women. AB - OBJECTIVE: To investigate the value of the combined use of vaginal ultrasonography and endometrial sampling in the office for the diagnosis of endometrial disease in postmenopausal women. METHODS: One hundred forty consecutive postmenopausal women presenting with uterine bleeding or endometrial cells on cervical cytology entered the study. Vaginal ultrasonography was used to measure the endometrial thickness, followed by use of the Pipelle endometrial sampler. Pipelle biopsy was not feasible in two patients. The results of hysteroscopy with biopsy or hysterectomy, performed within 6 weeks in all but 12 patients, were considered the final diagnosis. The accuracy of ultrasound and Pipelle was measured against the final diagnosis. RESULTS: The sensitivity of vaginal ultrasonography for endometrial disease was 98.2 and 82.0% if cutoff points for endometrial thickness of 2 and 4 mm, respectively, were used. All six patients with endometrial carcinoma had endometrial thicknesses exceeding 12 mm. Pipelle endometrial sampling had a sensitivity of 44.6% and a specificity of 98.5% for endometrial disease. All cases of endometrial carcinoma were detected by sampling in the office setting. CONCLUSION: This study illustrates the value of vaginal scanning in the diagnosis of endometrial disease in symptomatic, postmenopausal women. A 4-mm cutoff point for endometrial thickness seemed appropriate. The sensitivity of Pipelle sampling for endometrial carcinoma was excellent, but relatively weak for other endometrial disease because it failed to detect endometrial polyps and submucous myomas. The combined use of ultrasound and Pipelle sampling offers sufficient diagnostic information for most symptomatic postmenopausal women. PMID- 7862371 TI - Serum lipoproteins, insulin, and urinary prostanoid metabolites in normal and hypertensive pregnant women. AB - OBJECTIVE: To determine if hyperinsulinemia, hypertension, hypertriglyceridemia, and low levels of high-density lipoprotein (HDL) cholesterol are present in women with pregnancy-induced hypertension or preeclampsia. METHODS: Serum concentrations of insulin, uric acid, total and lipoprotein cholesterol, triglyceride, and apolipoproteins A-I and B were measured in 31 women with pregnancy-induced hypertension (eight with proteinuria) and in 21 healthy, pregnant, weight-matched controls at 30-39 weeks' gestation. The urinary excretion of the stable metabolites of prostacyclin (PGI2) (6-keto-prostaglandin [PG] F1 alpha and 2,3-dinor-6-keto-PGF1 alpha) and thromboxane A2 (TxA2) (thromboxane B2 and 2,3-dinor-thromboxane B2) was assessed in 17 women with pregnancy-induced hypertension and in eight controls. RESULTS: Women with pregnancy-induced hypertension exhibited 18% lower mean serum HDL2 cholesterol levels (0.9 versus 1.1 mmol/L, P < .05) and 65% higher mean triglyceride levels (3.3 versus 2.0 mmol/L, P < .05) compared to controls, whereas other serum lipid and apolipoprotein values did not differ significantly in the two groups. Mean serum insulin levels (13.3 versus 6.5 mU/L, P < .01) and uric acid levels (339.7 versus 231.2 mumol/L, P < .01) in patients with pregnancy-induced hypertension were significantly higher than those in the controls. Urinary output of PGI2 metabolites was reduced by 35-45% in patients with pregnancy-induced hypertension, whereas no differences were seen in the excretion of TxA2 metabolites. Serum HDL2 cholesterol concentrations correlated positively with 2,3 dinor-6-keto-PGF1 alpha excretion, and serum triglyceride concentrations correlated positively with 2,3-dinor-thromboxane B2 excretion. In addition, insulin levels correlated positively with triglyceride levels but negatively with HDL2 cholesterol concentrations. CONCLUSION: The metabolic characteristics (hypertriglyceridemia, hyperinsulinemia, hyperuricemia, low HDL2 cholesterol) in pregnancy-induced hypertension resemble the main features of the "insulin resistance syndrome." This may result in endothelial cell dysfunction as evidenced by PGI2 suppression. PMID- 7862372 TI - Decrease in myometrial beta-adrenergic receptors with prenatal cocaine use. AB - OBJECTIVE: To determine if cocaine use during pregnancy is associated with a reduction in the number or affinity of beta-adrenergic receptors in human myometrium. METHODS: Myometrium was obtained at cesarean delivery of five women who reported using cocaine during pregnancy and from ten controls. Saturation binding assays were performed on the myometrial membrane fractions using [125I] cyanopindolol to determine beta-adrenergic receptor concentration and affinity. The percentages of beta 1- and beta 2-adrenergic receptors were determined in three cocaine users and four control patients by performing competition binding assays using the beta 2 antagonist ICI 118,551. Results were compared using unpaired Student t tests. RESULTS: Women who reported using cocaine during pregnancy had a significantly lower mean (+/- standard deviation) concentration of myometrial beta-adrenergic receptors than did controls (22 +/- 8 versus 52 +/- 23 fmol/mg protein, respectively). There was no difference in the receptor affinity constants between cocaine users and controls (16 +/- 2 pmol/L for both groups). The percentages of beta 1- and beta 2-adrenergic receptors in the myometrium of the cocaine-use group and control group were similar: 86 +/- 1% beta 2 in the cocaine-use group and 83 +/- 7% beta 2 in the control group. CONCLUSION: Cocaine use during pregnancy may be associated with a down-regulation of beta-adrenergic receptors in human myometrium. This could result in a decreased capacity for uterine relaxation and, consequently, a predisposition to preterm labor. PMID- 7862373 TI - Maternal volume homeostasis in early pregnancy in relation to fetal growth restriction. AB - OBJECTIVE: To test the hypothesis that volume adaptation in pregnancies complicated by fetal growth restriction (FGR) is already abnormal very early in pregnancy. METHODS: In six pregnancies later complicated by FGR, volume homeostasis in the first 8 weeks was compared to that in ten normal pregnancies. Creatinine clearance, volume-dependent hormones, hemodilution-related variables, and ultrasonic cardiovascular dimensions were measured weekly between weeks 5 and 10, in the second and third trimesters, and postpartum. Differences between the two groups were analyzed by nonparametric tests. RESULTS: Very early in pregnancy, pregnancies complicated by FGR differed from normal pregnancies in the following ways: smaller left atrial diameter, smaller collapsible part of the inferior vena cava, lower serum sodium concentration, and smaller fall in serum creatinine and urea. CONCLUSION: Fetal growth restriction is preceded by defective volume adaptation very early in pregnancy. It appears that the maternal compensation mechanisms are unable to resolve the transient state of vascular underfill seen in this period in normal gestation. PMID- 7862374 TI - Down syndrome prevention program in a population with an older maternal age. AB - OBJECTIVE: To investigate the effect of a relatively high proportion of pregnant women 35 years and older on the efficacy of prenatal screening for Down syndrome. METHODS: We obtained information on normal and abnormal cytogenetic and maternal serum marker studies for 1990 and 1992 from all 11 public and two private cytogenetic laboratories operating in Israel. RESULTS: In the Jewish Israeli population, 16.2-17.1% of all pregnant women are at least 35 years old. Thus, prenatal testing of all pregnant women at least 35 years old could have identified 62.8-66.5% of all Down syndrome cases. Screening by maternal serum markers would classify 9.28% of pregnancies as being at high risk for Down syndrome (greater than 1:386 at birth). The percentage of Down syndrome cases detected prenatally increased from 78 of 147 (53%) to 123 of 163 (75%) as a result of the increased use of prenatal testing from 11.3% to 19.4% of all pregnancies in 1990 and 1992, respectively. CONCLUSIONS: In a population with a high proportion of mothers at least 35 years old, as in the Jewish population in Israel, screening by maternal serum markers instead of by maternal age alone would leave the Down syndrome detection rate unchanged, but would lower the amniocentesis rate from 16.2-17.1% to 9.28%. In addition to the reduction in the expected fetal loss as a result of post-amniocentesis spontaneous abortion, this policy would also pay the cost of maternal serum marker testing of the entire pregnant population. PMID- 7862375 TI - Uterine artery velocimetry and spontaneous preterm delivery. AB - OBJECTIVE: To evaluate if idiopathic spontaneous preterm delivery is associated with abnormal uteroplacental circulation, as assessed by Doppler velocimetry. METHODS: The study was carried out on 417 women who had Doppler velocimetry performed between 25-36 weeks' gestation and were subsequently delivered vaginally. The systolic-diastolic ratio (S/D) was computed for the uterine and umbilical arteries, and the outcomes of pregnancies with spontaneous preterm and term deliveries were compared. RESULTS: Uterine artery S/D was significantly higher (P < .0001) in the 31 patients delivered preterm, whereas no significant difference was observed in the umbilical S/D. Abnormal values of uterine S/D were detected in 58.1% of the preterm group, independent of the gestational age at examination. No significant increase in S/D was observed in patients hospitalized for preterm labor who delivered subsequently at term. Spontaneous preterm delivery was associated with increased uterine S/D among both pregnancies with small for gestational age fetuses and those with appropriately grown fetuses. CONCLUSION: Preterm delivery is associated with modifications of uterine artery Doppler velocimetry, suggesting that impaired trophoblastic invasion of the placental bed may play a role in determining preterm delivery. PMID- 7862376 TI - The use of color Doppler ultrasound to identify fetuses at increased risk for trisomy 21: an alternative for high-risk patients who decline genetic amniocentesis. AB - OBJECTIVE: To compare color Doppler ultrasound with real-time ultrasound to determine whether it increased the identification of fetuses with trisomy 21. METHODS: Consecutive fetuses with a second trimester risk greater than 1:270 for trisomy 21 were examined with real-time ultrasound (n = 1028) or real-time plus color Doppler ultrasound (n = 1028) before second trimester genetic amniocentesis. The type of abnormal ultrasound findings were compared between fetuses with normal and abnormal chromosomes. Using the Bayes theorem, the ultrasound-adjusted maternal age-related risk (posterior risk) for trisomy 21 was computed after a normal or abnormal real-time plus color Doppler examination. RESULTS: A significantly greater number of fetuses with trisomy 21 (87% [13 of 15] versus 29% [5 of 17], P < .002) were identified with real-time plus color Doppler than with real-time ultrasound. Color Doppler ultrasound identified a significantly higher rate of cardiovascular abnormalities in fetuses with trisomy 21 (60% [9 of 15] versus 12% [2 of 17], P < .008) than did real-time ultrasound. Identification of abnormal fetal anatomy using real-time plus color Doppler in patients 35 years and older increases the likelihood of detecting trisomy 21. A normal real-time plus color Doppler examination of the fetus decreases the risk for trisomy 21 to less than 1:270 until the maternal age of 42, above which the risk for trisomy 21 is greater than 1:270. CONCLUSION: Real-time plus color Doppler ultrasound examination of the fetus is an alternative for the identification of trisomy 21 for patients who may decline genetic amniocentesis based on their age-related risk. PMID- 7862377 TI - Plasma cell endometritis in women with symptomatic bacterial vaginosis. AB - OBJECTIVE: To evaluate the endometrial microbiology and histopathology in women with symptomatic bacterial vaginosis but no signs or symptoms of upper genital tract disease or other vaginal or cervical infections. METHODS: Endometrial biopsies were performed on 41 women complaining of vaginal discharge or pelvic pain at a sexually transmitted disease clinic. These women had neither culture nor serologic evidence of Neisseria gonorrhoeae or Chlamydia trachomatis infection. Twenty-two women with bacterial vaginosis diagnosed by Gram stain examination of vaginal fluid, but with neither signs nor symptoms of upper genital tract infection, were compared with 19 women who had no evidence of bacterial vaginosis on vaginal fluid Gram stain. Endometrial biopsies were evaluated for histopathologic evidence of plasma cell endometritis and were cultured for N gonorrhoeae, C trachomatis, aerobic and anaerobic bacteria, Mycoplasma species, and Ureaplasma urealyticum. RESULTS: Ten of 22 women with bacterial vaginosis had plasma cell endometritis, compared with one of 19 controls (odds ratio [OR] 15, 95% confidence interval [CI] 2-686; P < .01). Bacterial vaginosis-associated organisms were cultured from the endometria of nine of 11 women with and eight of 30 women without plasma cell endometritis (OR 12.4, 95% CI 2-132; P = .002). CONCLUSION: Plasma cell endometritis was frequently present in women with bacterial vaginosis and without other vaginal or cervical infections. This suggests the possibility of an association between bacterial vaginosis and nonchlamydial, nongonococcal, upper genital tract infection. PMID- 7862378 TI - Provision of primary-preventive health care services by obstetrician gynecologists. AB - OBJECTIVE: To determine the extent to which obstetrician-gynecologists serve as primary care providers for women 15 years and older. METHODS: Three national data bases were analyzed to determine if differences exist in the content of care provided to women during a general medical examination by three medical specialties. Reasons for medical visits by women to obstetrician-gynecologists were compared with other medical specialties, and women who rely on obstetrician gynecologists for their care were characterized demographically. Survey data on the self-perceived role of obstetrician-gynecologists as primary care providers were also examined. RESULTS: Obstetrician-gynecologists provided more office based, general medical examinations to women 15 years and older than either general-family practitioners or internists. This finding was also true for women of reproductive age, defined as those 15-44 years old. When asked if they considered themselves primary care providers or specialists, 48.3% of ACOG fellows designated the former. CONCLUSION: Obstetrician-gynecologists are important providers of primary and preventive care for women, and nearly half of all obstetrician-gynecologists consider themselves to be primary care providers. PMID- 7862379 TI - The reproducibility of the postcoital test: a prospective study. AB - OBJECTIVE: To determine the reproducibility of the postcoital test among trained observers. METHODS: Twenty-eight infertile patients presenting to the Brigham and Women's Hospital over a 1-year period were recruited for the study. After a standardized collection of specimens for the postcoital test, four fellowship trained reproductive endocrinologists evaluated six postcoital test characteristics and gave their overall impression of the test. Each observer was blinded to the patients' identities and clinical histories as well as to the ratings of the other observers. The six characteristics included an assessment of the cervical mucus by ferning, cellularity, spinnbarkeit, and consistency, and of sperm by total count per high power field and percent motility. Scoring was adapted from World Health Organization (WHO) criteria for semen-cervical mucus interaction. Statistical analysis included the kappa statistic to determine agreement among observers for postcoital test characteristics and the Mantel Haenszel test to determine the association between overall impression and the other test characteristics. RESULTS: Agreement among the four observers was best for sperm number and motility (39% of cases) and worst for cellularity, spinnbarkeit, and overall test impression (11, 14, and 14% of cases, respectively). The kappa statistic ranged from a low of 0.13 for cellularity, demonstrating poor reliability (95% confidence interval [CI] 0.03-0.23), to a high of 0.51 for sperm number, demonstrating fair reliability (95% CI 0.41-0.60). Only sperm number and percent motility were significantly associated with the overall impression (P < .001). CONCLUSIONS: In a blinded study, the characteristics of the postcoital test were found to have poor to fair reproducibility among trained observers using a standardized WHO scoring system. The observers' overall impressions of test quality correlated with sperm number and motility only. We question the validity of the postcoital test as a diagnostic tool in the evaluation of infertility. PMID- 7862380 TI - Use of GnRH agonist before hysterectomy: a cost simulation. AB - OBJECTIVE: To evaluate the potential savings in cost of care derived from performing vaginal hysterectomies instead of abdominal hysterectomies in selected women with fibroid uteri equivalent in size to a 14-18 week gestation. METHODS: Women 35-46 years of age undergoing hysterectomy for fibroid uteri were selected to allow application of conversion rates gained in a separate randomized study using leuprolide acetate depot 3.75 mg. Statewide public data for North Carolina's hospital discharges provided relative rates of hospital charges and leiomyomas for all hysterectomies, by age. Professional charges were omitted from the analysis. Estimated savings were projected to the national level. RESULTS: During 1992 in North Carolina, 18,110 inpatient hysterectomies were performed for women of all ages; 28.1% of these were for uterine leiomyomas. For women 35-46 years old (12.7% of all hysterectomies), there were 1904 abdominal and 390 vaginal hysterectomies; the mean total charge for abdominal hysterectomy was $5590, and $4732 for the vaginal alternative. These statewide data provide missing elements to allow a national estimate of the potential savings of using GnRH agonist preoperatively. The projected national savings, if 1987 utilization data are used, was $4.6 million, nearly 1.4% of the inpatient charges. The 1992 value of these savings is $6.7 million. CONCLUSION: The use of preoperative GnRH agonist therapy before hysterectomy for patients with a uterine size equivalent to a 14-18 week gestation represents a significant cost-saving alternative, increasing the use of vaginal hysterectomy and resulting in potential savings in direct inpatient medical care charges. PMID- 7862381 TI - Follicle-stimulating hormone concentrations in relation to active and passive smoking. AB - OBJECTIVE: To determine the association between various forms of tobacco exposure and ovarian status, as measured by FSH concentrations, in women 38-49 years old. METHODS: Two hundred ninety women between 38-49 years old, who had not had hysterectomy or oophorectomy, completed a self-administered questionnaire that included information on tobacco exposure and had serum FSH levels measured on days 2-4 of the menstrual cycle. Linear regression was used to assess the relation between FSH and tobacco exposure. RESULTS: Controlling for age and other factors, FSH concentrations were 66% higher among current smokers (geometric mean FSH 14.0 mIU/mL) and 39% higher among nonsmokers with passive smoke exposure (11.7 mIU/mL), compared to nonsmoking women without passive smoke exposure (8.4 mIU/mL). The estimated increase in FSH for each year of age was greater for current smokers than for nonsmokers (16 versus 6%, respectively). Ex-smokers did not have higher FSH concentrations, and there was no association between prenatal exposure to tobacco smoke and FSH. CONCLUSION: Both active and passive smoking are associated with elevated FSH concentrations in women 38-49 years old. The effect, limited to women with current exposure, is consistent with a shorter duration of the menopausal transition period. PMID- 7862382 TI - Subcutaneous tissue approximation in relation to wound disruption after cesarean delivery in obese women. AB - OBJECTIVE: To test the hypothesis that closure of the subcutaneous fat decreases the incidence of wound disruption after cesarean delivery. METHODS: Two hundred forty-five women with at least 2 cm of subcutaneous fat were randomized to closure of the Camper fascia or no closure with cesarean delivery. RESULTS: Complications leading to disruption or opening of the incision were classified as wound seromas in 28 women (11.4%) and as wound infections in 17 (7.0%). The relative risk (RR) of seroma formation in the subcutaneous closure group was 0.3 with a 95% confidence interval (CI) of 0.1-0.7 (5.1 versus 17.2%), a statistically significant difference. There was no significant difference in the incidence of wound infections in the two study groups. Overall, there was a significant difference in the incidence of wound disruption from all causes between the two groups: 14.5% in the subcutaneous closure group compared with 26.6% when the subcutaneous tissues were not reapproximated (RR 0.5, 95% CI = 0.3 0.9). CONCLUSION: Closure of the subcutaneous tissue can significantly reduce the rate of postoperative wound disruption in women with at least 2 cm of subcutaneous adipose tissue. PMID- 7862383 TI - Hypoglycemia: the price of intensive insulin therapy for pregnant women with insulin-dependent diabetes mellitus. AB - OBJECTIVE: To evaluate the risk of hypoglycemia associated with intensive insulin therapy of type I diabetes during pregnancy. METHODS: Eighty-four women with type I diabetes were recruited before 9 weeks' gestation and received intensive insulin therapy throughout pregnancy. Patients monitored glucose concentrations with memory glucometers, and insulin dosages were adjusted weekly accordingly. A detailed history of clinical hypoglycemic events was obtained at each weekly clinic visit. RESULTS: Clinically significant hypoglycemia requiring assistance from another person occurred in 71% of pregnant patients, with a peak incidence between 10-15 weeks. Severe hypoglycemia during the early weeks of embryogenesis was not associated with an increase in embryopathy. Glycemic control was similar in women with or without recurrent hypoglycemia, but glucose fluctuations were significantly greater in hypoglycemic women. CONCLUSION: Severe hypoglycemia is a significant maternal risk associated with intensive insulin therapy of pregnant women with type I diabetes. In women with recurrent episodes of hypoglycemia, the clear benefits of strict glycemic control must be weighed against the hazards of hypoglycemia. PMID- 7862384 TI - Glucose tolerance test periodicity: the effect of glucose loading. AB - OBJECTIVE: To test the hypothesis that glucose abnormality, as shown by glucose tolerance test (GTT) periodicity, is not affected by different glucose loads, allowing for the identification of gestational diabetes mellitus (GDM) under varying glucose challenges. METHODS: Eighty subjects were tested by multiple GTTs 1 week apart. Each woman served as her own control, undergoing a standard 3-hour, 100-g GTT; then, half of the subject group randomly underwent a 50-g and the other half a 75-g, 2-hour GTT. Subjects were classified using National Diabetes Data Group thresholds for the 100-g GTT. Those with two or more abnormal values were classified as gestational diabetic (GDM group); the rest of the women were considered to be nondiabetic. The projected time for the GTT to revert to fasting value, GTT periodicity, was then determined for each glucose load in the GDM and nondiabetic groups. RESULTS: All glucose values for the nondiabetic group were significantly lower at 1 and 2 hours than those for the GDM group, regardless of the glucose load (P < .04). There was a statistically significant difference within the GDM and nondiabetic groups between glucose values of the 100- and 50-g GTTs at 1 hour (P < .02) and between all loads at 2 hours (P < .04). The GTT periodicity for the 3-hour, 100-g test was significantly longer for patients with GDM, as shown previously (5.6 +/- 1.9 versus 3.2 +/- 1.7 hours, P < .0001). In addition, similar values were found for nondiabetic and GDM subjects for the 75-g (5.1 +/- 2 versus 3.6 +/- 1.8 hours, P < .04), but not the 50-g load (2.2 +/- .6 versus 1.34 +/- .8 hours, P < .01). CONCLUSION: Glucose tolerance test periodicity will identify subjects with GDM regardless of GTT load because the physiologic disturbance of glucose level measured by this time period remains comparably longer than in normal subjects. We speculate that the relatively shorter cycle of the 50-g load may reflect an insufficient challenge to pancreatic function. PMID- 7862385 TI - Interaction of angiotensin II and brain natriuretic peptide in the placentas of normal and diabetic women. AB - OBJECTIVE: To evaluate the effects of angiotensin II and brain natriuretic peptide on the placental vasculature of diabetic women. METHODS: Term placentas from five diabetic women and five nondiabetic controls were collected. Isolated placental cotyledons were perfused dually with fetal perfusion pressure as an index of vascular response. The effect of angiotensin II (10(-10)-10(-5) mol/L bolus injection) was established in the fetal-placental vasculature of all placentas in the absence or presence of brain natriuretic peptide (10(-8) mol/L final concentration). Data were analyzed using repeated measures analysis of variance and paired t test where appropriate. RESULTS: A significant vasoconstrictor response to angiotensin II was achieved in placentas of both diabetic and nondiabetic women (P < .001); however, the angiotensin II-induced increase in perfusion pressure was significantly greater in the diabetic group (P < .01). Significant attenuation of vasoconstrictor response to angiotensin occurred in the presence of brain natriuretic peptide in placentas of both nondiabetic (P < .0025) and diabetic (P < .025) women, but the effect was more prominent in the diabetic group. CONCLUSION: The in vitro placental vasculature of diabetic women is more sensitive to angiotensin II than is the in vitro placental vasculature of nondiabetic women. The attenuation exerted by brain natriuretic peptide on angiotensin II-induced vasoconstriction is more prominent in placentas from diabetic women compared to those from nondiabetic women. PMID- 7862386 TI - Heparin versus normal saline as a peripheral line flush in maintenance of intermittent intravenous lines in obstetric patients. AB - OBJECTIVE: To compare heparin sodium (100 United States Pharmacopeia U/mL) with 0.9% sodium chloride for use in the maintenance of intermittent intravenous (IV) devices during pregnancy. METHODS: Women at 26-34 weeks' gestation who required serial phlebotomy were assigned randomly to heparin or normal saline flush, administered in a double-blind fashion. Catheter sites were examined and flushed with the study solution at least once every 6 hours. Partial thromboplastin times (PTTs) were measured at catheter insertion and 48 hours later. Statistical analysis was performed with Student t test, Mann-Whitney U test, Fisher exact test, log-rank, and X2 analysis, as appropriate. RESULTS: There was a significant increase in catheter patency rate at 48 and 72 hours in the heparin group (26 of 31 versus 17 of 33, and 21 of 31 versus nine of 33, respectively; P < .01). In addition, there was a significantly lower rate of catheter complications in the heparin group (four of 31 versus 13 of 33; P < .01). There were no differences in PTTs. CONCLUSION: During pregnancy, dilute heparin flush to maintain patency of intermittent IV site devices results in the following: a greater catheter patency rate at 48 and 72 hours after insertion of the catheter, a lower rate of catheter complications requiring therapy, and no alteration in PTT. PMID- 7862387 TI - Enhanced antenatal detection of group B streptococcus colonization. AB - OBJECTIVE: To improve culture methods for the detection of group B streptococcus colonization. METHODS: This study prospectively compared the standard culture medium, a blood agar plate, to a selective culture medium, Todd Hewitt broth with antibiotics, and compared vaginal culture with rectal culture at the first prenatal exam. RESULTS: Of the 383 vaginal swabs received for evaluation of the two culture media, 78 (20.4%) were positive for group B streptococcus. The detection rates of the blood agar plate method and the Todd Hewitt broth with antibiotics were 64.1 and 97.4%, respectively. Using the Todd Hewitt broth with antibiotics, an additional 94 patients were cultured vaginally and rectally. Twenty-nine (30.9%) had positive cultures. The rate of detection was 58.6% for the vaginal culture, 89.7% for the rectal culture, and 100% for both culture sites combined. CONCLUSION: These data indicate that culture detection of group B streptococcus can be improved by using both a selective broth medium and a dual vaginal and rectal culture. PMID- 7862388 TI - Universal screening for group B streptococcus: recommendations and obstetricians' practice decisions. AB - OBJECTIVE: To determine how obstetricians' opinions regarding universal screening of pregnant women for group B streptococcus (GBS) and their responses to positive culture results vary from American Academy of Pediatrics recommendations, and to determine the physician characteristics that predict divergent opinions. METHODS: One hundred ninety-four practicing obstetricians in the middle Tennessee region were queried by a mail survey. They were asked if they agreed with universal screening for GBS and to indicate whether they would prescribe antibiotics for women in labor, represented by six scenarios that differed with respect to presence or absence of preterm labor, premature rupture of membranes (ROM), prolonged ROM, and a positive GBS cervical culture. They were also asked to describe their practice and personality characteristics. RESULTS: Completed surveys were returned by 135 of 194 obstetricians (70%). Although only 28% of the respondents agreed with routine prenatal screening for GBS, most (74%) said they would treat a patient on the basis of a positive culture alone. Other risk factors, when added to a positive culture, slightly increased the decision to treat (from 74 to 88%). Multiple logistic regression, used to assess the relative effect of clinical and physician characteristics on treatment decisions, revealed that chemoprophylaxis for GBS was predicted most strongly by a positive culture at 28 weeks' gestation followed by prolonged ROM and preterm labor. Practicing in an urban location and seeing fewer than 20 patients per day also influenced the decision to treat. CONCLUSION: Although most obstetricians in the middle Tennessee region do not believe in universal screening, most will prescribe intrapartum antibiotics on the basis of a positive screening culture. However, other clinical risk factors and physician characteristics significantly and independently affect the decision to treat as well. PMID- 7862389 TI - Baseline serum and cerebrospinal fluid magnesium levels in normal pregnancy and preeclampsia. AB - OBJECTIVE: To determine whether baseline cerebrospinal fluid magnesium levels in preeclampsia differ from those in normal pregnancy, and to ascertain whether pre treatment cerebrospinal fluid magnesium levels correlate with serum levels, which would suggest a baseline alteration in the blood-brain barrier in preeclampsia. METHODS: When spinal analgesia or anesthesia was administered for delivery, serum and cerebrospinal fluid magnesium levels were determined in 20 normal gravidas and 20 preeclamptic women not treated with magnesium sulfate. Data were analyzed by two-sided Student t test and regression analysis. RESULTS: Mean (+/- standard deviation) cerebrospinal fluid magnesium level for preeclamptic patients was 2.23 +/- 0.09 mEq/L, which was not significantly different from controls. Regression analysis revealed no significant correlation between cerebrospinal fluid and serum magnesium levels for either normal or preeclamptic gravidas. CONCLUSION: During the third trimester, there is no difference in baseline, pre-treatment cerebrospinal fluid magnesium levels in preeclamptic patients compared to normal subjects, and no correlation between cerebrospinal fluid and serum magnesium over the range of baseline values. PMID- 7862390 TI - Fetal nucleated cells in maternal peripheral blood after delivery in cases of fetomaternal hemorrhage. AB - OBJECTIVE: To determine how long fetal nucleated cells can be detected in maternal peripheral blood after delivery in cases of fetomaternal hemorrhage, using fluorescence in situ hybridization or polymerase chain reaction. METHODS: Nucleated cells with Y chromosomes were analyzed in 90 blood samples using fluorescence in situ hybridization with a Y-chromosome-specific DNA probe. The samples were obtained from 15 mothers (gravida 1), who were delivered of normal male neonates at University of Tsukuba Hospital, Japan, with fetomaternal hemorrhage 1 and 7 days, and 1, 3, 6, and 12 months after delivery. The 15 mothers were selected if fetal cells were detected above the ratio of one fetal cell per 3000 mothers' cells at 1 day after delivery. Polymerase chain reaction amplifying two different Y-specific fragments (a 102 base-pair fragment in the pHY10 vector, which was a highly repetitive sequence, and a single-copy, Y specific 198 base-pair fragment) was also carried out for the analysis of genomic DNA from the same samples. RESULTS: Seven days and 1 month after delivery, Y positive cells were detected in nine and four of 15 samples, respectively. No cells with the hybridization signal were detected in any of the 45 samples obtained 3 months or more after delivery. When we performed the polymerase chain reaction experiment amplifying the single-copy Y-specific fragment, none of the 45 samples after 3 months or more showed the expected band. However, from the same 45 samples, four obtained from different mothers showed positive results by amplification of the fragment in the pHY10 vector. Because multiple samples taken from these mothers before the collection of the positive samples showed negative results in the three experiments, these findings strongly suggest that the observed positive results were false-positives. CONCLUSION: Fetal nucleated cells in maternal peripheral blood become undetectable 3 months after delivery in most, if not all, cases of fetomaternal hemorrhage. PMID- 7862391 TI - The cognitive outcome of full-term small for gestational age infants at late adolescence. AB - OBJECTIVE: To assess the cognitive and academic performance of adolescents who were born small for gestational age (SGA) at term. METHODS: A 17-year historical prospective study was done by matching neonatal data of 1758 infants to the results of the medical and intelligence assessment performed at age 17 years at the army draft board medical examination in Israel. The results of children born SGA (weight at term birth below the third percentile) were compared to those of children who were born appropriate for gestational age (AGA). RESULTS: After adjustment by a multiple linear regression analysis, the mean (+/- standard error of the mean) intelligence test scores were 103.1 +/- 2.9 versus 105.8 +/- 1.5 (P = 0.3) for the males and 100.3 +/- 2.5 versus 104.7 +/- 1.6 (P < .03) for the females. Males born SGA at term were found to have lower educational achievements (having less than 12 years of schooling or attending a vocational school) compared with the AGA group. The odds ratio for this finding after adjustment by a logistic regression analysis was 2.40 (95% confidence interval 1.07-5.39; P < .03). Intranatal events were not found to have an effect on the measured neurodevelopmental outcome. CONCLUSION: Infants born SGA at term have an increased risk for lower cognitive performance and schooling achievements than those born AGA; this result seems to be unrelated to their intranatal course. PMID- 7862392 TI - Intrauterine ultrasonography with a high-frequency probe: preliminary report. AB - Intrauterine ultrasonography was performed using miniature probes and high frequency ultrasound to examine the possible clinical applications of this technique to gynecology. There were 44 women in the study population (age 19-76; ten with a normal uterus, nine fibromyoma, 15 endometrial cancer, ten cervical cancer). The probe was easily introduced into the endometrial cavity in 36 subjects (81.8%). No notable complications were encountered. In subjects with a normal uterus, the endometrium in the secretory phase showed a clearly demarcated hyperechoic area, and higher resolution was obtained than with transvaginal scanning. In patients with fibromyomas, myoma nodules were not clearly visualized because of the attenuation of ultrasound. Myometrial invasion of endometrial cancer was estimated correctly in ten of the 11 patients in which the lesion was visualized. In the subjects with cervical cancer, intracervical scanning was completed in only five cases, and an endocervical lesion was identified in three cases. Intrauterine ultrasonography with a high-frequency miniature probe may be a useful tool, especially in the preoperative evaluation of endometrial cancer and possibly in infertility practice. However, this modality does not appear to be satisfactory for cervical lesions. PMID- 7862393 TI - First-trimester endocervical irrigation: feasibility of obtaining trophoblast cells for prenatal diagnosis. AB - We sought to determine the feasibility of obtaining trophoblast cells for first trimester prenatal diagnosis using endocervical irrigation. We studied 20 pregnant patients between 7-10.5 weeks' gestation who presented for elective pregnancy termination. Under ultrasound guidance, a specially designed plastic catheter was advanced to the level of the internal cervical os. Gentle flushing and aspiration was performed with 3 mL of normal saline. The material obtained was fixed and stained. A placental pathologist identified trophoblast cells using light microscopy. In another five cases, we attempted to culture the endocervical washings. Trophoblast cells were identified by microscopy after staining the cultured material with an anti-alpha-hCG-antibody bound stain. In ten of 20 cases (50%), trophoblast material was retrieved on irrigation. Of the five additional cases on which culture was attempted, trophoblast was successfully cultured in one, the results were equivocal in two, and culture was unsuccessful in the other two. Trophoblast cells for prenatal diagnosis can be obtained in a significant percentage of cases by first-trimester endocervical irrigation. The advantages of irrigation include technical simplicity, brief duration (less than 3 minutes), and suitability to first-trimester diagnosis. Further testing is necessary to determine the risks. PMID- 7862394 TI - Laparoscopic treatment of interstitial pregnancy. AB - The conventional treatment of interstitial pregnancy has been cornual resection of hysterectomy by laparotomy. We have used a laparoscopic approach to treatment of interstitial pregnancy, consisting of cornual excision in four patients and salpingotomy incision via the myometrium in another. In all five cases, the procedure was associated with minimal bleeding and no complications. PMID- 7862395 TI - Does prenatal care improve birth outcomes? A critical review. AB - OBJECTIVE: To evaluate evidence that prenatal care improves birth outcomes. DATA SOURCES: The MEDLINE data base was searched for appropriate studies for the years 1966-1994; a review of published studies was also conducted. METHODS OF STUDY SELECTION: Published observational and experimental studies of prenatal care that met specified criteria were selected. DATA EXTRACTION AND SYNTHESIS: Studies were graded based on the system used by the United States Preventive Services Task Force. Data were assessed using established criteria for the evaluation of prenatal interventions: temporal relationship, biologic plausibility, consistency, alternative explanations, dose-response, strength of association, and cessation effects. Current evidence did not satisfy the criteria. CONCLUSION: Prenatal care has not been demonstrated to improve birth outcomes conclusively. However, policymakers deciding on funding for prenatal care must consider these findings in the context of prenatal care's overall benefits and potential cost effectiveness. Cost-effective reductions in low birth weight deliveries may be beyond the statistical powers of detection of current studies. PMID- 7862396 TI - The passage of Florida's statute on assisted reproductive technology. PMID- 7862397 TI - Development of a cesarean delivery risk score. PMID- 7862398 TI - Incidence of disc hemorrhage in glaucoma. PMID- 7862399 TI - Training for ocular anesthesia. PMID- 7862400 TI - Recurrence of macular holes. PMID- 7862401 TI - Transconjunctival blepharoplasty. PMID- 7862402 TI - Appreciating Ophthalmology's international connection. PMID- 7862403 TI - Intraocular pressure elevation associated with inhalation and nasal corticosteroids. AB - BACKGROUND: The ocular hypertensive response to corticosteroids is well established. Elevated intraocular pressure (IOP) secondary to corticosteroids by nasal spray or inhalation has rarely been reported. RESULTS: Three patients showed a possible ocular hypertensive response to beclomethasone dipropionate by nasal spray or inhalation. In two patients, the IOP returned to pretreatment levels after discontinuing nasal corticosteroid spray. One patient required medication to control IOP with continued inhaled corticosteroid. One patient later demonstrated an ocular hypertensive response to oral steroids. CONCLUSION: Corticosteroids by nasal spray or inhalation may cause ocular hypertension in susceptible patients. The authors recommend surveillance of IOP in patients using these medications. PMID- 7862404 TI - Association of intraocular pressure and myopia in children. AB - PURPOSE: While elevated intraocular pressure (IOP) is associated with myopia in adults, its potential influence on the growth of eyes in juveniles without glaucoma is controversial. To address this issue, a possible relation between IOP and refraction in children was sought. METHODS: A cross-sectional survey of IOP was conducted in children presenting to the Division of Pediatric Ophthalmology at The Children's Hospital of Philadelphia for a complete eye examination. Measurement of IOP was attempted in all children, including those with amblyopia, prematurity, and strabismus. Exclusion criteria were abnormalities of the posterior pole and/or conditions such as cataract that precluded assessment of refractive error. For analysis, myopia was defined as a spherical equivalent of more than 1 diopter (D) of myopia. Logistic regression was used to assess the association between other patient characteristics and presence of myopia. RESULTS: Intraocular pressure testing was attempted in all age groups, but was more successful in older children. Reliable readings were obtained on 321 subjects. The mean age was 9.8 years, with a mean IOP of 17.3 mmHg in the right eye and 17.2 mmHg in the left and a mean spherical equivalent of +0.2 D in the right eye and +0.1 D in the left. Increasing age, a family history of myopia, and amblyopia were associated myopia. Increasing IOP also was related to myopia. Even when patients with amblyopia, strabismus, and prematurity were exclude, age, family history of myopia, and IOP again were associated with myopia. CONCLUSIONS: These results indicate that IOP in children may be higher in myopic than nonmyopic eyes. Whether IOP could contribute to the mechanisms causing the abnormal eye growth of childhood myopia requires further study. PMID- 7862405 TI - Congenital hereditary endothelial dystrophy associated with glaucoma. AB - BACKGROUND: Three children, ranging in age from 2 to 6 months, had diffuse and homogeneously opaque corneas, clinically consistent with congenital hereditary endothelial dystrophy. Bilateral elevated intraocular pressure (IOP) was a feature in all three children. METHODS: Initially, all patients underwent glaucoma surgery to reduce IOP. Subsequently, a penetrating keratoplasty was performed in one eye of each patient to clear the visual axis. The excised corneal button was examined by light microscopy and by transmission and scanning electron microscopy. RESULTS: Postoperatively, all patients maintained clear corneal grafts. Results of histopathologic examination showed an absence of the endothelial cell layer in all patients. The presence of a variably thick collagenous layer posterior to the anterior banded zone of Descemet's membrane and the absence of endothelial cells were noted on transmission electron microscopy. Scanning electron microscopy confirmed absent, or scanty, and abnormal endothelial cells. CONCLUSION: The authors describe three patients with a clear association between congenital glaucoma and congenital hereditary endothelial dystrophy. This combination should be suspected where persistent and total corneal opacification fails to resolve after normalization of IOP. PMID- 7862406 TI - Association of congenital microcoria with myopia and glaucoma. A study of 23 patients with congenital microcoria. AB - BACKGROUND: Congenital microcoria, a bilateral condition of the iris dilatator, is defined as a pupil with a diameter of less than 2 mm when looking at a distant object. Although it is usually a hereditary condition resulting from autosomal dominant transmission with no marked difference between the sexes, it is sometimes sporadic. The ocular abnormalities associated with this condition (myopia, astigmatism, and glaucoma) have never been linked to the malformation. METHOD: Forty-two members of a family were examined: 23 had microcoria and 19 did not. The two groups were studied to identify symptoms of the condition and its associated abnormalities. RESULTS: There was a very strong correlation between microcoria and myopia (Fisher's exact test, P < 0.00001), between microcoria and astigmatism (Fisher's exact test, P < 0.0001), and between microcoria and glaucoma (Fisher's exact test, P = 0.011). CONCLUSIONS: There is a statistical correlation among myopia, glaucoma, and microcoria, and the disorders are associated with the condition in a nonfortuitous way. The functional prognosis for microcoria appears to be extremely poor because of refractive disorders and, particularly, a link between microcoria and glaucoma that is difficult to explain. PMID- 7862407 TI - Long-term visual results of children after initially successful vitrectomy for stage V retinopathy of prematurity. AB - PURPOSE: To assess the effectiveness of vitrectomy for stage V retinopathy of prematurity (ROP) at the authors' institution, 33 patients with ROP who had initially successful total or partial anatomic retinal attachments (51 eyes) were evaluated for visual function and long-term anatomic stability. In addition, this study was an attempt to differentiate levels of visual function in children with very low vision and attendant developmental delays. METHODS: Visual function was assessed before retinal examination by an experienced pediatric vision specialist. The behavioral visual assessment was divided into seven segments with two to five tasks in each segment designed to establish a level of functional vision, ranging from light perception to form identification (and ambulation). The status of the retina was classified by the patient's retinal surgeon. RESULTS: The median follow-up was 61 months, and median age at the time of examination was 68 months. Of 51 eyes treated, form identification was achieved in 5, and all five patients had ambulatory vision. Of 51 eyes, 15 had no light perception, 11 had light perception, 6 could localize light, 10 could follow lights, and 4 were able to detect form. Only one eye in ten children with comparable ROP in each eye underwent surgery, and vision improved in six of ten of the surgical eyes. Redetachment was high, with 35 retinas totally or partially detached and only 13 retinas fully attached 61 months after surgery. CONCLUSION: The visual results are very low and disappointing. Initially successfully attached retinas can detach. There is some evidence that vitrectomized eyes function better than nonvitrectomized eyes. There is also evidence that visual function lower than form identification is useful to these children and that they are able to use their limited vision better than previously though. PMID- 7862408 TI - The prevalence of age-related maculopathy in the Rotterdam Study. AB - PURPOSE: To determine the prevalence of age-related maculopathy in an elderly population in The Netherlands. METHODS: Fundus photographs of 6251 participants of the Rotterdam Study, a single-center prospective follow-up study in persons 55 to 98 years of age, were reviewed for the presence of drusen, pigmentary abnormalities, and atrophic or neovascular age-related macular degeneration. RESULTS: The prevalence of at least one drusen of 63 microns or larger increased from 40.8% in persons 55 to 64 years of age to 52.6% in those 85 years of age or older. Similarly, the prevalence of the following abnormalities increased significantly in these age categories: drusen of 125 microns or larger from 4.8% to 17.5%, retinal pigment epithelial hypopigmentations from 3.5% to 9.0%, and increased retinal pigment from 3.7% to 15.3%. Atrophic or neovascular age-related macular degeneration was present in 1.7% of the total population. Atrophic age related macular degeneration increased from 0.1% in persons 55 to 64 years of age to 3.7% in those 85 years of age or older. Neovascular age-related macular degeneration increased from 0.1% to 7.4% in these age groups. No sex differences were observed for these lesions. CONCLUSIONS: The prevalence of atrophic or neovascular age-related macular degeneration is 1.7%. In those 55 years of age or older, the prevalence increases strongly with age and it is similar in men and women. Neovascular age-related macular degeneration was twice as common as atrophic age-related macular degeneration. These findings suggest that age related maculopathy may be less common in this European population than in similar populations in the United States. PMID- 7862409 TI - Combined pars plana vitrectomy-lensectomy and open-loop anterior chamber lens implantation. AB - PURPOSE: To investigate the effectiveness of open-loop, one-piece, flexible, Kelman-style, all-polymethylmethacrylate (PMMA) anterior chamber intraocular lenses (AC IOLs) in patients undergoing pars plana vitrectomy surgery for a variety of vitreoretinal disorders. METHODS: Fifteen patients (6 women and 9 men) underwent combined pars plana vitrectomy with insertion of an open-loop AC IOL. Postoperative results were evaluated. RESULTS: The average preoperative visual acuity of 20/360 (logMAR scale, 1.25 +/- 0.80) improved to 20/52 (logMAR scale, 0.42 +/- 0.35) after an average follow-up of 10.2 months (range, 1-41 months). Of 15 eyes, 7 (47%) achieved a visual acuity of better than 20/40. There was no evidence of glaucoma exacerbation or corneal decompensation. Visual acuity was limited primarily by chronic cystoid macular edema in 4 (27%) of 15 eyes. CONCLUSION: In this preliminary series of patients, open-loop, flexible, all PMMA, Kelman-style AC IOLs appear to be well tolerated and represent a viable, simple alternative to transscleral fixation of a posterior chamber IOL or surgical aphakia in patients undergoing vitrectomy surgery. PMID- 7862410 TI - Imaging of macular diseases with optical coherence tomography. AB - BACKGROUND/PURPOSE: To assess the potential of a new diagnostic technique called optical coherence tomography for imaging macular disease. Optical coherence tomography is a novel noninvasive, noncontact imaging modality which produces high depth resolution (10 microns) cross-sectional tomographs of ocular tissue. It is analogous to ultrasound, except that optical rather than acoustic reflectivity is measured. METHODS: Optical coherence tomography images of the macula were obtained in 51 eyes of 44 patients with selected macular diseases. Imaging is performed in a manner compatible with slit-lamp indirect biomicroscopy so that high-resolution optical tomography may be accomplished simultaneously with normal ophthalmic examination. The time-of-flight delay of light backscattered from different layers in the retina is determined using low coherence interferometry. Cross-sectional tomographs of the retina profiling optical reflectivity versus distance into the tissue are obtained in 2.5 seconds and with a longitudinal resolution of 10 microns. RESULTS: Correlation of fundus examination and fluorescein angiography with optical coherence tomography tomographs was demonstrated in 12 eyes with the following pathologies: full- and partial-thickness macular hole, epiretinal membrane, macular edema, intraretinal exudate, idiopathic central serous chorioretinopathy, and detachments of the pigment epithelium and neurosensory retina. CONCLUSION: Optical coherence tomography is potentially a powerful tool for detecting and monitoring a variety of macular diseases, including macular edema, macular holes, and detachments of the neurosensory retina and pigment epithelium. PMID- 7862411 TI - Reproducibility of topographic measurements of the macula with a scanning laser ophthalmoscope. AB - BACKGROUND: The Heidelberg retina tomograph, a scanning laser ophthalmoscope that uses confocal optics to provide high resolution of images, is able to scan the retina in three dimensions to obtain quantitative topographic measurements. The authors evaluated its usefulness for measuring macular lesions by determining the reproducibility of its topographic measurements at the macula. METHODS: For each of ten healthy patients, the authors took five images with the patient's right eye undilated and five with the eye cyclopleged and dilated. As a measure of reproducibility, the standard deviation of height measurements for the same location at the macula was calculated for each patient and then the pooled standard deviation for all patients was calculated. The authors performed similar calculations for the mean depth within a contour line. RESULTS: The pooled standard deviation for height measurements was 47.4 microns in undilated eyes and 36.0 microns in cyclopleged, dilated eyes. The authors obtained an extremely low standard deviation of 2.2 microns when the software calculated relative differences between measurements, such as the mean depth within a contour line. When the average of three height measurement values on 1 day was compared with the average of the three values on another day, the 95% confidence interval was +/- 58.7 microns for mean height values and +/- 3.7 microns for mean depth values within a contour line. CONCLUSIONS: The authors obtained good reproducibility for height measurements with the Heidelberg retina tomograph and excellent reproducibility when the instrument calculated relative differences in height measurements. The authors recommend that patients, especially young patients, be dilated and cyclopleged to obtain lower variability of measurements. The scanning laser ophthalmoscope could potentially be used to quantify small changes in retinal lesions. PMID- 7862412 TI - Results of rhegmatogenous retinal detachment repair in cytomegalovirus retinitis with and without scleral buckling. AB - PURPOSE: To determine if scleral buckling is of any benefit in surgical repair of cytomegalovirus (CMV)-associated retinal detachment if combined with vitrectomy, silicone oil, and inferior midperipheral endolaser. MATERIALS AND METHODS: Twenty two consecutive eyes with CMV-associated retinal detachments were repaired with vitrectomy and endolaser to all breaks and to the inferior midperipheral retina using silicone oil without scleral buckling (group 1, control group) between July 1987 and May 1992. Results were compared with another series of 56 consecutive eyes undergoing vitrectomy, silicone oil injection, endolaser to all breaks, and 360 degrees encircling scleral buckling (group 2, study group) between June 1992 and July 1993. RESULTS: Total retinal reattachment rates were 84% for group 1 and 86% for group 2. Rates of macular reattachment were 91% for group 1 and 91% for group 2. Mean best postoperative refracted visual acuity was 20/66 for group 1 and 20/67 for group 2. Median best postoperative refracted visual acuity was 20/74 for group 1 and 20/80 for group 2. These differences in results between the two groups were not statistically significant. Mean postoperative refractive error was +3.95 for group 1 and +4.92 for group 2. Patients who underwent surgery with the macula attached had a better postoperative visual outcome. CONCLUSION: Scleral buckling may not be necessary in CMV-related retinal detachment if repaired with vitrectomy, silicone oil, and inferior midperipheral endolaser. Elimination of scleral buckling may reduce intraoperative time, patient morbidity, and the risk of an accidental needle stick. Patients with macula-on retinal detachments also should be considered for surgery before macular detachment. PMID- 7862413 TI - A peripherin/retinal degeneration slow mutation (Pro-210-Arg) associated with macular and peripheral retinal degeneration. AB - BACKGROUND: Mutations in the peripherin/retinal degeneration slow (RDS) gene have been identified in patients with retinitis pigmentosa and pattern macular dystrophy. The authors initially examined a large family affected with both peripheral and macular degeneration, inherited as an autosomal dominant trait. Screening for peripherin/RDS mutations identified a previously unreported nucleotide alteration in all of the affected individuals. Two additional families later were found to have this same mutation. METHODS: DNA samples from the members of three unrelated families were screened for peripherin/RDS mutations by denaturing gradient gel electrophoresis of the polymerase chain reaction amplified peripherin/RDS coding sequences. The sequence change that was detected was further characterized by DNA sequencing. Family members were examined and evaluated with psychophysical and electrophysiologic methods. RESULTS: A proline to arginine mutation in codon 210 of peripherin/RDS was found in all clinically affected individuals. Macular changes included extensive geographic atrophy, pigment epithelial changes, and/or drusen. The proline to arginine mutation was not found among 100 healthy individuals, making it unlikely to be a nondisease causing polymorphism. CONCLUSIONS: The authors identified a novel peripherin/RDS gene mutation associated with autosomal dominant retinal degeneration in patients from three different families. The largest family showed a broad variability in the expressivity of the mutation. The overlap of clinical features with those of age-related maculopathy highlights the need to consider photoreceptor-specific genes as potential factors in the etiology of the latter condition. PMID- 7862414 TI - Ocular vaso-occlusive disease in primary antiphospholipid syndrome. AB - PURPOSE: To evaluate the ocular involvement in patients with the primary antiphospholipid syndrome. METHODS: The authors performed a cross-sectional ophthalmologic study of 17 patients with the primary antiphospholipid syndrome. Retinal fluorangiography was performed in 13 patients. RESULTS: Visual symptoms were described by ten patients. Visual acuity was markedly decreased in five eyes. Conjunctival telangiectases and microaneurysms, in addition to single instances of bilateral episcleritis and limbal keratitis, were the anterior segment findings. Fundus abnormalities were present in 15 patients. Venous tortuosity was the most common finding but there were instances of optic disc edema, vitreous hemorrhages, cotton-wool spots, vitreous bands, serous detachment of the macula, and retinal capillary abnormalities. Fluorangiography showed vaso occlusive retinopathy in six eyes (5 patients, 29%). Choriocapillary vessel occlusion was observed in two eyes (1 patient) and binocular reticular degeneration of pigmentary epithelium was present in another case. CONCLUSION: The eye is frequently involved in the primary antiphospholipid syndrome, and serious ocular damage may occur. Detailed ophthalmologic evaluation is warranted in these patients. PMID- 7862415 TI - Erbium:YAG laser surgery of the vitreous and retina. AB - PURPOSE: These studies evaluated an erbium:YAG laser for transection of vitreous membranes, retinotomy, and incision and ablation of epiretinal membranes. METHODS: Elevated vitreous membranes, detachments, and epiretinal membranes were induced in rabbit eyes. An erbium:YAG laser, emitting at a wavelength of 2.94 microns and equipped with a flexible fiber and endoprobes with tips ranging from 75 to 375 microns, was used to perform vitreous membrane transections, retinotomies, and epiretinal membrane incisions and ablations in nontransmitting aqueous media with the endoprobe in proximity to the tissue. Ablations of epiretinal membranes also were performed in transmitting media, including air and perfluoro-N-octane with the endoprobe elevated above the membrane. RESULTS: Twenty-five vitreous membrane transections were made in 16 eyes at distances ranging from 0.5 to 4.5 mm from the retina with radiant exposures ranging from 2 to 50 J/cm2 with nonhemorrhagic retinal damage in a single transection. Sharp, linear retinotomies were created successfully in five eyes. Epiretinal membrane ablations were performed with radiant exposures ranging from 1.8 to 22.6 J/cm2. In aqueous media, results of microscopic examination showed partial- to full thickness ablation with a maximum lateral thermal damage of 50 microns. In air- and perfluoro-N-octane-filled eyes, there was increased lateral damage with desiccation of residual tissue. In 12 aqueous-filled eyes, 18 linear incisions were successfully performed, with retinal nonhemorrhagic damage in 2 eyes and hemorrhage in 5. CONCLUSION: The erbium:YAG laser may provide new approaches to maneuvers performed in vitreoretinal surgery. PMID- 7862416 TI - Intraocular irrigating solutions. A randomized clinical trial of balanced salt solution plus and dextrose bicarbonate lactated Ringer's solution. AB - BACKGROUND: Two intraocular irrigating solutions which differ principally by the presence of oxidized glutathione were compared in this randomized, masked, prospective study to discern differences in preservation of endothelial cell size. METHODS: Sixty-four patients undergoing extracapsular cataract extractions were randomized between two irrigating solution groups, Balanced Salt Solution (BSS) Plus (n = 30) and dextrose bicarbonate lactated Ringer's solution (n = 34). Preoperative and postoperative endothelial specular photomicrographs were analyzed for cell size and hexagonality, and the two groups were compared using repeated measures analysis of variance. RESULTS: Fifty-eight subjects (91%) completed the 2-month study. Change in cell size for the BSS Plus group (n = 28) (mean +/- standard error, 29.4 +/- 12.3 microns2) was not significantly different from the dextrose bicarbonate lactated Ringer's solution group (n = 30) (27.5 +/- 12.9 microns2) (P = 0.92). Groups did not differ significantly in percent hexagonality (P = 0.57) or in the variability of cell size (P = 0.61). CONCLUSION: The presence of glutathione in BSS Plus and other minor electrolyte differences between the solutions is not more advantageous with regard to endothelial cell size than dextrose bicarbonate lactated Ringer's solution for standard extracapsular cataract surgery. Cost per 500-microliters bottle of BSS plus is $62 compared with $9.80 for dextrose bicarbonate lactated Ringer's solution. PMID- 7862417 TI - Corneal integrity after refractive surgery. Effects of radial keratotomy and mini radial keratotomy. AB - PURPOSE: Mini-radial keratotomy (mini-RK) involves limiting the extent of radial incisions to within 3.5 mm from the center of the central clear zone, compared with incisions that extend close to or beyond the limbus, as with "conventional" RK. This study was designed to determine if shorter incision length reduces the likelihood of corneal rupture after blunt trauma. METHOD: Sixteen fresh human anterior segments were divided into four groups and mounted onto an artificial anterior chamber. Four corneas with no incisions were used as controls, four received regular four-incision RK, four received four mini-RK incisions, and four received eight mini-RK incisions. Incisions extended from the 3.0-mm central clear zone to 1 mm inside the limbus (regular RK), or from the 3.0-mm central clear zone to the 7.0-mm mark (mini-RK). A pump slowly infused the artificial anterior chamber with a balanced salt solution while the pressure was continuously monitored with an electronic pressure transducer. The maximum pressure and the site of the rupture were recorded. RESULTS: Control corneas ruptured at the limbus, whereas all surgical eyes ruptured at incision sites. The corneas subjected to mini-RK ruptured at significantly higher pressures than corneas that had undergone regular RK (P < 0.01). CONCLUSION: Reducing incision length appears to reduce the likelihood of corneal rupture as intraocular pressure is increased. Mini-RK may be advantageous for patients at high risk for ocular trauma. PMID- 7862418 TI - Dry eye with only decreased tear break-up time is sometimes associated with allergic conjunctivitis. AB - PURPOSE: The authors' clinical experience has suggested that there is a form of dry eye with only decreased tear break-up time, which is associated with allergic conjunctivitis. The current study was performed to verify this hypothesis. METHOD: The authors recruited patients with two types of dry eye syndrome, those with only decreased tear break-up (BUT type) and those with positive vital staining (staining type). Individuals without any symptoms or signs served as controls. All subjects were compared regarding symptoms, Schirmer and tear clearance test results, conjunctival papillary formation, antigen-specific serum IgE level (s-IgE), and goblet cell density of the palpebral conjunctiva. Antigen induced allergic conjunctivitis was produced in guinea pigs, and histopathologic changes of the conjunctiva were examined. RESULTS: Patients with the BUT-type dry eye syndrome were younger and their symptoms were as severe as the staining type. The Schirmer and tear clearance test results were better, and the papillary formation and s-IgE were observed more than in the BUT type. The average goblet cell density in the BUT-type syndrome was 625.4 +/- 193.2/mm2, which was significantly less than 1005.6 +/- 294.5/mm2 in the controls (P < 0.01). The average goblet cell density was significantly decreased in the allergic animals (10.40 +/- 1.11/0.2 mm) compared with that of the controls (16.21 +/- 0.26/0.2 mm) or the anti-allergic drug-treated group (13.69 +/- 0.30/0.2 mm) (P < 0.01). CONCLUSION: These results support the authors' hypothesis that decreased break-up time is in part associated with the decreased goblet cell density caused by allergic conjunctivitis. PMID- 7862419 TI - Evaluation of 0.05% levocabastine versus 4% sodium cromolyn in the allergen challenge model. AB - PURPOSE: This study was conducted to evaluate the efficacy of 0.05% levocabastine compared with 4% cromolyn for treating allergic conjunctivitis induced by ocular allergen challenge. METHODS: Subjects who met all entry criteria and reacted positively to ocular allergen challenge at two previous visits (n = 50) received placebo in one eye and cromolyn in the fellow eye, four times daily for 2 weeks. On day 18, subjects received the final dose of cromolyn in the pretreated eye and one drop of levocabastine in the fellow eye. Subjects were challenged and evaluated after 3, 5, and 10 minutes. Four hours after drug administration, subjects were rechallenged and evaluated after 3, 5, and 10 minutes. RESULTS: Levocabastine was significantly more effective than cromolyn in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and 4-hour rechallenge (P < 0.05). CONCLUSION: These results suggest that levocabastine is superior to cromolyn for treating allergen-induced conjunctivitis and has a duration of action of at least 4 hours. PMID- 7862420 TI - Prognostic factors of vision in patients with Behcet disease. AB - BACKGROUND: Behcet disease is a chronic, recurrent, inflammatory disorder characterized by the triad of oral and genital ulcers and ocular lesions. The etiology is unknown. Although many of these patients become blind, some have good vision all their life. METHODS: To attain more accurate data on the prognosis of these patients, the authors studied 52 Japanese patients (101 eyes) seen at Kyushu University Hospital between 1980 and 1990. At the first visit, patients ranged in age from 21 to 61 years; at onset, they ranged in age from 17 to 55 years; and the disease duration at first visit was from 0 to 22 years. Thirty five of the 101 eyes had a visual loss of more than five lines or the patients became blind. The authors divided the subjects into two groups--favorable group and unfavorable group. If an eye had more than five lines of visual loss or the patient became blind 3 years after the first visit, it was placed in the unfavorable group, and if not, it was classed in the favorable group. Thirty-two factors determined from clinical records were used to select statistically significant risk factors for visual loss, using univariate analysis and multivariate logistic regression analysis. RESULTS: Univariate analysis showed the following four factors that were significantly different between favorable and unfavorable groups: sex, disease interval, other complications, and skin lesions (first year). Multivariate analysis showed that the following seven factors had mutually independent contributions to visual loss: skin lesions; arthritis; posterior attacks; other complications (experienced), including gastrointestinal, vascular, and central nervous system lesions; female sex; disease interval; and anterior attacks. The first four factors have effects of losing vision, whereas the others are related to vision retention. CONCLUSION: The authors find that skin lesions, arthritis, posterior attacks, and other complications are linked to loss of vision, whereas female sex, disease interval, and anterior attacks are related to retention of vision. PMID- 7862421 TI - Direct cyclopexy for traumatic cyclodialysis with persisting hypotony. Report in 29 consecutive patients. AB - BACKGROUND: Traumatic or postoperative cyclodialysis frequently is associated with persisting ocular hypotony, causing morphologic changes and visual loss. METHODS: The authors retrospectively analyzed the data of 29 eyes of 29 patients who underwent consecutive direct surgical cyclopexy for hypotonus cyclodialysis between 1980 and 1993 at the authors' institution. Cyclopexy was performed by directly suturing the ciliary body to the scleral spur under a scleral flap. RESULTS: The cyclodialysis clefts were posttraumatic (26 eyes) or postsurgical (3 eyes), extended for 3.6 +/- 1.7 clock hours (range, 1.5-9.5 clock hours), and were most frequently located superiorly. In eight eyes, argon laser photocoagulation of the cyclodialysis cleft (1-11 sessions) was performed before surgical cyclopexy but failed to permanently close the clefts. Preoperatively, all eyes showed persisting ocular hypotony with intraocular pressure of 3.1 +/- 2.3 mmHg (range, 0-8 mm Hg), macular edema, and disc swelling. Postoperatively, intraocular pressure was 14.0 +/- 3.7 mmHg (range, 6-20 mmHg), and visual acuity improved in 25 eyes (86%) and remained unchanged in 4 (14%) because of posttraumatic posterior segment problems. In 14 eyes, painful reversible pressure spikes of up to 58 mmHg developed during the first postoperative days, but no persisting secondary glaucoma was observed during further follow-up of 37.7 +/- 35.9 months (range, 2-134 months). All ten phakic eyes that were refracted preoperatively and postoperatively showed hyperopic shifts of more than 1 diopter after cyclopexy. CONCLUSIONS: Direct surgical cyclopexy is a successful treatment for large hypotonus cyclodialysis clefts that are unresponsive to or too large for laser photocoagulation. Painful early postoperative pressure spikes are frequent, but the development of glaucoma seems to be very uncommon. Postoperative visual acuity may be compromised due to posterior segment sequelae of preceding ocular trauma. PMID- 7862422 TI - Ultrasound biomicroscopic imaging of the effects of YAG laser cycloablation in postmortem eyes and living patients. AB - PURPOSE: The authors performed a series of experiments designed to determine if early effects of YAG laser cycloablation could be detected by ultrasound biomicroscopy in postmortem eyes and living patients. They also designed an apparatus that allowed simultaneous ultrasound biomicroscopic imaging of YAG laser cycloablation. METHODS: Treated and untreated regions of postmortem eyes treated with YAG cycloablation were imaged and compared. Treatment was placed at varying distances from the limbus in postmortem eyes and the resulting effects imaged. Histologic examinations were performed after imaging. Six living patients had ultrasound biomicroscopy before and after YAG cycloablation. An apparatus combining contact YAG laser and ultrasound biomicroscopy was used in postmortem eyes. RESULTS: Early treatment effects imaged included ciliary epithelial disruption, ciliary epithelial separation, and bubble formation. Ultrasound biomicroscopic findings varied with the distance of treatment from the limbus and were maximal below the treatment site. Results of histologic examination showed close correlation to the ultrasound biomicroscopic images. Similar findings to those found in postmortem eyes were found in living patients after treatment. The apparatus combining contact YAG and ultrasound biomicroscopy allowed realtime imaging of effects of YAG laser cycloablation. CONCLUSIONS: The ability of ultrasound biomicroscopy to detect changes associated with cyclodestructive procedures potentially could provide us with a method of improving treatment precision and correlating treatment effect with clinical response. PMID- 7862423 TI - Optic nerve axon count and axon diameter in patients with ocular hypertension and normal visual fields. AB - BACKGROUND: At postmortem examination, the authors obtained eight eyes of five individuals with elevated intraocular pressure and normal visual fields to study the axon count and mean axon diameter. METHODS: Automated image analysis was used to calculate the total axon count and mean axon diameter per nerve and per nerve segment for each eye. The authors applied the method of identification analysis to compare each study eye with a corresponding normal eye of patients of the same age. RESULTS: There was no statistically significant difference compared with control subjects for total axon count or segmental axon count for any of the eyes. Two eyes showed a statistically significant difference for mean axon diameter for the whole nerve but not for individual segments of the nerve. CONCLUSIONS: Some eyes subjected to varying duration and magnitude of intraocular pressure elevation with normal visual fields may maintain normal axon counts and mean axon diameters. PMID- 7862424 TI - Intrapapillary and peripapillary hemorrhage in young patients with incomplete posterior vitreous detachment. Signs of vitreopapillary traction. AB - PURPOSE: The authors describe a benign condition characterized by intrapapillary and subretinal peripapillary hemorrhage, incomplete posterior vitreous detachment with persisting attachments to the disc, and preservation of optic nerve function in young patients. METHODS: Eight patients 11 to 42 years of age with no or mild symptoms (blur, spot, or smudge) were referred for disc hemorrhage; seven of these patients were Asian. All underwent complete ophthalmologic examination, including detailed slit-lamp microscopy; particular attention was paid to vitreous attachments. RESULTS: Superficial hemorrhage occurred predominantly in the superior hemidisc and was often striking in appearance. Subretinal hemorrhage occurred at the superonasal disc margin in six patients and was centered inferonasally in two. Discs were generally small, mildly dysplastic, and tilted; all were mildly elevated. The posterior vitreous body was separated from the retina but remained attached to the disc. Six patients had subtle visual field abnormalities in the involved eye. The hemorrhages resolved without sequelae or impairment of vision. During a 6-month follow-up, no patient progressed to complete vitreous detachment, retinal tear, or retinal detachment or required surgery to release traction. CONCLUSION: The authors postulate that vitreopapillary traction traumatized disc vessels, causing hemorrhage in and around the disc. The superior hemidisc received the shearing force of detachment, which tore superficial vessels; transmission of the force through the retina caused subretinal bleeding. Posterior vitreous detachment remained incomplete because of tenacious vitreopapillary attachments. Mildly dysplastic discs, as in the young patients with myopia reported here, may have unusual vitreous attachments, predisposing them to the occurrence of and trauma from premature vitreous separation. The condition described is benign and requires no further evaluation or intervention. PMID- 7862425 TI - Case of perforated peptic ulcer treated conservatively. AB - We report a patient fifty-one-year old man with peptic ulcer which was treated conservatively. His chief complaints were epigastric discomfort and tarry stool. On admission, no fever was noted, the abdomen was flat and extremely hard, tenderness was noted, and peritoneal rebound was absent. Laboratory data on admission were all normal except for a slightly elevated CRP level. Oral intake was suspended and the patient received infusion. The chest X-ray film on the following day revealed free air, and the diagnosis of perforation of the upper digestive tract was confirmed; however, the symptoms and signs of peritonitis diminished. Therefore, he was treated conservatively. This case suggests that the conventional indications for emergency surgery for perforated peptic ulcer should be re-evaluated. PMID- 7862426 TI - Anti-Ro/SS-A antibody-positive interstitial pneumonitis in a non-lupus patient. AB - We describe a 42-year-old anti-Ro/SS-A antibody positive non-lupus patient who developed interstitial pneumonitis in combination with several common clinical features with previously reported lupus pneumonitis patients whose anti-Ro/SS-A antibodies were positive, while whose antinuclear antibodies were negative. We consider that these patients may belong to a same new clinical entity. A variety of characteristic manifestations related to anti-Ro/SS-A antibodies has been reported in patients with systemic lupus erythematosus (SLE) and other connective tissue diseases [1] [2], and an association between these antibodies with pulmonary parenchymal involvement has been reported by Hedgpeth and Boulware in patients with SLE [3] [4]. We report here a 42-year-old non-lupus male patient with pulmonary fibrosis who presented with anti-Ro/SS-A antibodies. PMID- 7862427 TI - Effect of intracellular pH and two growth factors, epidermal growth factor and human hepatocyte growth factor, on DNA synthesis in non-regenerating and regenerating hepatocytes and hepatoma cells. AB - I examined the effects of intracellular pH (pHi) and the growth factors, epidermal growth factor (EGF) and human hepatocyte growth factor (HGF), on DNA synthesis in non-regenerating hepatocytes, regenerating hepatocytes and hepatoma cells. Non-regenerating and regenerating hepatocytes were isolated from the livers of intact adult rat and of the adult rat 24 hours after 70% hepatectomy, respectively. Hep G2 cells, a human hepatoma cell line, was employed as hepatoma cells. Regenerating hepatocytes and Hep G2 cells, but not non-regenerating hepatocytes displayed increased DNA synthesis with increasing pHi in the absence of EGF and HGF. However, non-regenerating hepatocytes displayed little increase, regenerating hepatocytes displayed substantial increase in DNA synthesis with increasing pHi in the presence of EGF or HGF. In contrast, Hep G2 cells displayed decreased DNA synthesis in the presence of HGF but not EGF. These findings indicate that pHi influences the fashion of proliferation in hepatocytes and cancer cells. EGF and HGF stimulate DNA synthesis in hepatocyte and inhibit that in cancer cell, suggesting that increasing pHi and administration of these growth factors may be one of the effective treatment for hepatoma. PMID- 7862428 TI - Comparison of assay procedures for solubilized thyroid hormone receptor. AB - Seven procedures for the assay of thyroid hormone receptor were compared. Receptors from rat liver nuclei were incubated with [125I] triiodothyronine (T3), and the hormone bound to the receptors was separated by the different methods and its radioactivity was counted. Column chromatography on Sephadex G-25, filtration on nitrocellulose membranes, glass filters, or diethylaminoethyl cellulose disks, and vortex/centrifugation with use of hydroxyapatite, Dowex AG 1 x 8 resin, or a mixture of charcoal and dextran were used. Filtration on a nitrocellulose membrane was the most sensitive and accurate method. The use of Dowex AG 1 x 8 was the easiest. Filtration on a glass filter was the best when samples were particulate. PMID- 7862429 TI - Modulation of protein kinase C in aorta of spontaneously hypertensive rats with enalapril treatment. AB - We measured protein kinase C (PKC) activity, levels of PKC alpha enzyme and PKC alpha mRNA in aortic media of spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto rats (WKY) and enalapril treated SHR (enal-SHR) to examine whether hypotensive treatment of enalapril modulates PKC in aortic media of SHR. The cytosolic PKC activity in crude samples of aortic media of SHR was higher than in those of WKY or enal-SHR (p < 0.01) and was closely associated with blood pressure (r = 0.84, p < 0.001). The membrane PKC activity was detected in samples of SHR, but virtually no activity was detected in samples of WKY or enal-SHR. The cytosolic PKC activity in DEAE column purified samples of SHR was also higher than in those of WKY or enal-SHR (p < 0.01). The PKC alpha enzyme levels (74-kDa and 77-kDa protein) detected by immunoblot were higher in SHR than in WKY or enal SHR (p < 0.01). The mRNA levels of PKC alpha were higher in SHR than in WKY (p < 0.01) and were much decreased in enal-SHR (p < 0.01). Thus, PKC activity, PKC alpha and its mRNA levels were higher in aortic media of SHR than those in WKY and these increased levels were reversed with enalapril treatment. Considering the pivotal roles of PKC in the mechanism of cellular proliferation and the pathogenesis of hypertension, these results provide clues in understanding the pathogenesis of hypertension, mechanisms of vascular hypertrophy in hypertension and the beneficial effects of angiotensin converting enzyme inhibitor in the treatment of hypertension. PMID- 7862430 TI - Intercostal muscle pedicle flap for prophylaxis against bronchopleural fistula after pulmonary resection. AB - Between April 1982 and March 1994, we did 384 pulmonary resections for lung cancer. Until March 1991, we did 249 pulmonary resections in which none of the bronchial stumps were reinforced; nine patients developed bronchopleural fistula (incidence, 4%). After April 1991, bronchial stumps of 135 patients were reinforced by an intercostal muscle pedicle flap for prophylaxis against bronchopleural fistula. Only one patient developed it (incidence, 1%). In these two periods, the proportion of patients in stage IIIa or more advanced stages increased from 24% to 41%, resulting in more extensive operations and more patients being given chemo-radiation therapy in the perioperative period. These are risk factors for bronchopleural fistula, but the incidence of the fistula decreased. These results suggest that reinforcement of the bronchial stump with an intercostal pedicle flap is useful for prophylaxis against developing bronchopleural fistula. PMID- 7862431 TI - [Therapeutic use of dapsone in dermatitis herpetiformis (Duhring) and in certain inflammatory skin diseases]. AB - After a historical review the authors give a summary about the possibility of clinical practice of Dapson dependly on 20 year literature. They emphasize the newest knowledge of the mechanism of action. The diseases in which the Dapson may be successful are expounded. The adverse effects are presented. In the centre- like the prototype of Dapsone-therapy--there is the dermatitis herpetiformis. PMID- 7862432 TI - [Anterior pituitary responsiveness in central Cushing disease and in Cushing syndrome caused by adrenal cortex tumors, as well as in simple obesity]. AB - To evaluate whether the PRL, TSH and gonadotropin secretion is altered in conditions with elevated body mass index, 7 patients with central Cushing's disease before and after transsphenoidal surgery, 7 untreated patients with Cushing's syndrome caused by adrenal adenoma, 17 simplex obese (obese) women and 9 non-obese controls (all females, aged 18-45 years) were tested with TRH (200 micrograms i.v. bolus) and GnRH (100 micrograms i.v. bolus) and the hormone responses were measured. There were no differences in the basal pituitary hormone secretion among the groups. In obese subjects the PRL response was reduced as compared to untreated patients with corticotrop pituitary adenoma. No significant differences of TSH release could be observed among the groups, whereas serum total T4 levels were higher in obesity than in patients with hypercorticism either caused by pituitary or adrenal Cushing's syndrome. No differences were found in the LH response, but the stimulated FSH release was lower in obesity, in patients with central Cushing's disease after transsphenoidal surgery and in patients with primary Cushing's syndrome as compared to the normal controls. PMID- 7862433 TI - [Congenital cholelithiasis]. AB - The author screened 6000 newborns with ultrasound and two gallstones have found (in age 1 and 2 days). He found numerous floating echogenic spots in the gallbladder of three other newborns. The spots and one of two gallstones disappeared, the other gallstone did not changed during the first 6 months of life. The author thinks, the maternal predisposing factors have importance in the formation of intrauterine gallstones. These factors disappear after delivery and the connatal gallstones often disappear spontaneously. If they don't, the author thinks it worthy to try to resolve them with ursodeoxycholate. PMID- 7862434 TI - [Retrospective study 10 years after plastic surgery for sacrococcygeal pilonidal sinus]. AB - The authors give a brief summary on the etiology and pathomechanism of the sacrococcygeal pilonidal sinus. They have distinguished the congenital, cystic deformation (dermoid cyst) from the pilonidal sinus which is considered to be an adventitious illness. During ten years (1976-1985) 208 patients were operated on with the method the authors applied. Only one early recurrence was registered and 7.2% of the patients recovered from secondary healing. Delayed recurrences were analysed according to questionnaires. From 151 of the questionnaires only three male patients complaints referred to delayed recurrence. PMID- 7862435 TI - [Prenatal diagnosis of thanatophoric dysplasia]. AB - The authors report a case of a thanatophoric dysplasia associated with hydramnios diagnosed at 32 weeks' gestation by sonographic investigation. The final diagnosis was derived from radiological and hystological findings. The authors underline that the identification of a specific osteochondrodysplasia is quite difficult and postulates interdisciplinary cooperation between gynecologists, neonatologists, radiologists and pathologists. More effective counselling of affected families is the major purpose of all the efforts involved. PMID- 7862436 TI - [Current trends in the diagnosis, therapy and care of hypertension]. PMID- 7862437 TI - [Alexis Carrel (1873-1944)]. PMID- 7862438 TI - [Medals honoring Lajos Markusovsky]. PMID- 7862439 TI - Kinase activities of c-Mos and v-Mos proteins: a single amino acid exchange is responsible for constitutive activation of the 124 v-Mos kinase. AB - The Mos protein kinase is a serine-/threonine-specific protein kinase with a crucial role in meiotic cell divisions in vertebrates. Several oncogenic derivatives of the c-Mos protein have been discovered in murine retroviruses. These proteins have acquired mutations and exhibit different degrees of protein kinase activity in vitro. In an attempt to understand the factors governing Mos protein kinase activity we have compared the kinase activities of the wild-type c Mos protein and two v-Mos proteins (strain HT1 and MSV124) after expression in insect cells. Only the 124 v-Mos protein showed kinase activity in vitro as measured by autophosphorylation, vimentin phosphorylation or by phosphorylation and activation of MAP kinase kinase. By domain swapping and site-directed mutagenesis we identified a single point mutation in the 124 v-Mos protein (Arg145-->Gly) which is responsible for its constitutive activity. This residue is located in the alpha-helix C of the kinase domain close to the ATP binding fold and is conserved in all known c-Mos proteins. Introduction of the corresponding mutation into HT1 v-Mos and into murine c-Mos activated both proteins for autophosphorylation, vimentin phosphorylation and for signalling via MAP kinase kinase in vitro. We hypothesize that the Arg145-->Gly mutation found in 124 v-Mos mimicks a conformational change which might be an obligatory step in the activation of c-Mos in vivo. PMID- 7862440 TI - Regulation of lineage restricted haemopoietic transcription factors in cell hybrids. AB - SCL, GATA-1, GATA-2 and GATA-3 encode lineage restricted haemopoietic transcription factors. We have previously shown that SCL, GATA-1 and GATA-2 are expressed in multipotent progenitors prior to lineage commitment, but are down regulated during granulocyte/monocyte differentiation. The phenomenon of gene extinction in cell hybrids may reveal negative regulatory mechanisms operating during normal differentiation. We have therefore analysed the regulation of SCL, GATA-1, GATA-2 and GATA-3 in cell hybrids formed by the fusion of cell lines representing different haemopoietic lineages. Expression of GATA-3 was extinguished in both human and murine erythroid x T cell hybrids, an observation which suggests that erythroid cells contain factors capable of repressing GATA-3 expression. By contrast expression of SCL, GATA-1 and GATA-2 was not extinguished in erythroid x T or in erythroid x B cell hybrids. These data suggest that T cells and B cells do not contain trans-acting factors capable of down-regulating expression of SCL, GATA-1 or GATA-2, and therefore raise the possibility that a 'hit and run' mechanism may repress these genes during normal haemopoiesis. HpaII sites within the SCL promoter were unmethylated in erythroid cells but methylated in T cells. Erythroid x T and erythroid x B cell hybrids contained both methylated and unmethylated SCL promoters, thus implicating a heritable cis acting mechanism in the regulation of the SCL gene in lymphoid cell lines. These results provide the first analysis of SCL and GATA gene regulation in stable cell hybrids. PMID- 7862441 TI - Isolation and characterization of a chicken homolog of the c-ret proto-oncogene. AB - The c-ret proto-oncogene encodes a receptor tyrosine kinase that plays important roles in human disease and in normal mammalian development. Mutations in the human RET gene are associated with multiple endocrine neoplasia syndromes and Hirschsprung's disease in humans, while targeted mutagenesis of murine c-ret resulted in severe developmental abnormalities affecting the excretory and peripheral nervous systems. To examine the evolutionary conservation of the ret protein sequence and its developmental expression pattern, we isolated and sequenced cDNA clones of chicken c-ret and examined its expression in chick embryos and adult tissues. The cytoplasmic domains of chicken and human ret were relatively well conserved (91% similar), but the extracellular domains were more divergent (68% similar), although the conservation of cysteine residues in this region suggests a conserved secondary structure. As in mouse and human, chicken c ret encodes two protein isoforms. The number and sizes of the transcripts were similar to those in human and mouse cells, and during chick embryogenesis, c-ret mRNA was observed in many of the same sites as in the mouse, including the Wolffian duct and ureteric bud, the enteric, dorsal root, sympathetic and facioacoustic ganglia, and the ventral spinal cord. Evolutionary differences in expression were observed in the trigeminal ganglion, the ventral roots of the spinal cord, the mesenchymal cells of the branchial arches and the adult testes. The results are discussed with regard to the role of the ret receptor in normal development and disease. PMID- 7862442 TI - Adenovirus E1A-induced apoptosis elicits a steep decrease in the topoisomerase II alpha level during the latent phase. AB - The human KB derivative cell line MA1, established by introduction of the adenovirus E1A 12S cDNA linked to the hormone-inducible promoter, elicits apoptosis upon treatment with dexamethasone. The cell lines partially refractory to apoptosis were established by introducing the expression plasmid for the adenovirus E1B 19k protein to MA1 cells. After induction of E1A in MA1 cells by dexamethasone, the level of p53 increased to about 10-fold within 24 h, and morphological changes characteristics of apoptosis began to be observed within 48 h. Most of cells were killed at 72 h releasing apoptotic bodies. The level of topoisomerase II alpha began to decrease steeply within 36 h, preceding the onset of DNA degradation while its mRNA level unchanged throughout the apoptotic process. E1B 19k protected the decrease in topoisomerase II alpha as well as DNA fragmentation depending on its expression levels. Topoisomerase II alpha is induced specifically at G2/M, and computer search revealed the presence of cyclin B type destruction box in topoisomerase II alpha. These results strongly suggest that E1A or E1A stabilized p53 induces apoptosis by targeting topoisomerase II alpha to the ubiquitination pathway and E1B 19k alleviates its action. PMID- 7862443 TI - A variant form of cyclin-dependent kinase 2 (Cdk2) in a malignantly transformed rat thyroid (FRTL-Tc) cell line. AB - Cyclin-dependent kinase 2 (Cdk2) controls the transition from the G1 to the S phase in the mammalian cell cycle. We found by immunoblotting that anti-Cdk2 antibodies recognize three Cdk2 proteins (of 33, 34 and 39 kDa) in FRTL-5 and FRTL-Tc cells (malignantly transformed FRTL cells). Although 33 kDa protein is a phosphorylated form of 34 kDa protein previously reported, the nature of 39 kDa protein is unknown. In order to determine the nature of this protein, we screened a FRTL-5 cDNA library. Two cDNA clones of the rat homologue (rat Cdk2-alpha and beta) of human Cdk2 were isolated. The open reading frame of rat Cdk2-alpha cDNA encoded a protein with 428 amino acids and has a high degree of conservation with human Cdk2. The calculated molecular weight of Cdk2-alpha protein is 33892 Da. The rat Cdk2-beta cDNA was identical to Cdk2-alpha cDNA except that it had extra 144 bp; this coincided with insertion of 48 amino acids into Cdk2-alpha protein between Met 196 and Val 197. The calculated molecular weight of Cdk2-beta protein is 39087 Da. Northern blot analysis indicated that the sizes of rat Cdk2-alpha and -beta mRNAs are approximately 2.5 kb and 3.0 kb, respectively. Partial proteolytic mapping showed that Cdk2-beta gene product is 39 kDa Cdk2 in the immunoblotting. We also found that Cdk2-beta protein binds to cyclin A and suc1 proteins. During G1-S phase in FRTL-Tc cells, Cdk2-alpha protein level is constant, but is gradually phosphorylated. In contrast, the level of Cdk2-beta protein increases through the S phase and decreases at the early G2 phase. These results suggest that a variant form of Cdk2 protein might be required for entry into the S phase of the cell cycle in FRTL-Tc cells. PMID- 7862444 TI - Transcriptional repression by the C-terminal domain of p53. AB - We have previously shown that monomeric p53 can transactivate target genes in vivo and that C-terminal fragments of p53 are oncogenic. To further elaborate these findings a series of C-terminal truncations of p53 was generated. The transactivation capacity and the ability of the truncated p53 to suppress oncogene-mediated transformation were studied. We found that p53 truncated at amino acid 303 (p53wtdl303) can still function in both assays, though less efficiently than full length wild type (wt) p53. Transforming C-terminal fragments inhibited transactivation induced by full length wt p53. Surprisingly, they also inhibited transactivation by wtdl303, with which they do not share any overlapping sequences. Furthermore, the C-terminal fragments repressed the transactivation domains of several viral and cellular transcriptional activators. These data raise the possibility that the C-terminal domain of p53 may compete with the p53 transactivation domain for a common basal transcription factor. PMID- 7862445 TI - p53 gene mutations inside and outside of exons 5-8: the patterns differ in breast and other cancers. AB - Most studies of mutations in the p53 tumor suppressor gene in tumors have examined only exons 5-8. Our laboratory previously found 64 mutations in exons 5 8 of the p53 gene in 194 primary breast cancers. Herein, we report 18 additional mutations found outside of exons 5-8. Mutations are present in exons 4, 9 and 10, and flanking splice junctions, but not in the promotor region or in exons 1, 2, 3 and 11. No missense mutations are found outside of exons 5-8. Instead, there is a predominance of frameshift mutations with lesser numbers of nonsense and splice site mutations. In contrast, the majority of mutations in exons 5-8 in this sample are missense changes and all of these are at amino acids that are identical in the 11 known p53 sequences that represent about 1.6 billion years of evolutionary divergence. The difference in mutational pattern between these two regions of the p53 gene is due to a lack of missense mutations and inframe microdeletions outside of exons 5-8. A review of our database of p53 mutations (De Vries et al., in preparation) shows that the patterns of mutation inside and outside of exons 5-8 differ in other types of cancers as well. The paucity of missense mutations in exons 2-4 and 9-11 in breast and other cancers (even at amino acids identical throughout p53 gene evolution) suggest that at least some missense mutations result in a phenotype other than malignant transformation. These data also illustrate the importance of examining identical exons when comparing the pattern of p53 gene mutations in different populations. PMID- 7862446 TI - fra-2 promoter can respond to serum-stimulation through AP-1 complexes. AB - fra-2 (fos-related antigen-2) expression is detected at a basal level even in growth-arrested chicken embryo fibroblasts (CEF), but upon serum-stimulation high levels of its transcripts are transiently observed. This induction is delayed and prolonged compared to that of c-fos. Transient expression experiments in CEF using a series of constructs of chicken fra-2 promoter region linked to the CAT reporter gene indicated previously that serum response element (SRE) is not required for full serum inducibility. In this report, we show that constructs in which the CRE-like sequence and both AP-1 binding sites are disrupted lack serum inducibility, suggesting that either of these enhancers is important in serum induction of fra-2. In growth-arrested CEF, small amounts of Fra-2/c-Jun complex bind to the AP-1 consensus sequences in fra-2 promoter, while a significant part of the enhanced AP-1 binding activity after 60-120 min of serum stimulation is attributable to c-Fos/c-Jun heterodimer. At later times Fra-2/c-Jun again becomes the main complex. Transient expression assays in F9 cells indicated that c-Fos/c Jun heterodimers have strong stimulatory effects on fra-2 promoter activity, while Fra-2/c-Jun complex has lower transcriptional activity than that of c-Jun homodimer. These results suggest that c-Fos (induced at earlier times) and c-Jun proteins are at least partly responsible for serum-induced expression of fra-2. PMID- 7862447 TI - Inhibition of tumor cell proliferation in vitro and in vivo by exogenous p110RB, the retinoblastoma tumor suppressor protein. AB - Reconstitution of retinoblastoma gene (RB) deficient tumor cells with RB generally leads to growth suppression in vitro and/or reduced tumorigenicity in nude mice. An alternate approach to gene replacement is the delivery of the RB gene product (p110RB) into cells lacking its expression. In this report we demonstrate that exogenously added p110RB is taken up by and localized to the nucleus of cultured cells and has growth suppression properties similar to endogenous RB. RB-negative (RBneg) tumor cells are preferentially growth inhibited while most RB-positive (RBpos) tumor cells and normal cells are much less sensitive. We have extended these studies to relevant nude mouse xenograft models for human lung cancer. Local or systemic administration of p110RB inhibits tumor growth in treated animals. These results represent the first use of a tumor suppressor protein as a potential cancer therapeutic. PMID- 7862448 TI - A role for c-Abl in c-myc regulation. AB - c-Abl, a nonreceptor tyrosine kinase, appears to play a role in cell cycle progression, cell proliferation and differentiation. Mice homozygous for a mutation in c-abl (ablml), show pleiotropic abnormalities, including neonatal death, developmental defects, susceptibility to infection and dehydration (Schwartzberg et al., 1991). However, the exact substrates of c-Abl and the signal transduction pathways it might initiate are not known. We have examined how c-Abl affects c-myc expression by studying ablml mice. Quantitative riboprobe analyses demonstrated that in the heart, liver, thymus, brain, testes, intestines and lung, there were no differences in the steady-state level of c-myc RNA between the ablml mice and littermate controls. However, in adrenal glands, kidneys and splenic B cells, c-myc RNA levels were decreased approximately 50% compared to littermate controls. Induction of c-myc mRNA following activation of splenic B cells with LPS is also defective in ablml splenocytes. Finally, we show that c-Abl can directly transactivate c-myc transcription. These results suggest that c-Abl is involved in the normal transcription regulation of c-myc in selected tissues and that decreased c-myc RNA could be one cause of abnormalities in the ablml mice. PMID- 7862449 TI - Retroviral transduction and oncogenic selection of a cDNA encoding Dbs, a homolog of the Dbl guanine nucleotide exchange factor. AB - A retroviral vector was used to transfer a large library of cDNAs from the 32D murine hemopoietic cell line to NIH3T3 fibroblasts, for the purpose of selecting cDNAs that induce oncogenic transformation. One highly transformed colony arising in the infected NIH3T3 cell culture contained a provirus with a 1900 bp cDNA insert. After recovery and reincorporation into a retroviral vector, this cDNA induced rapid morphological transformation and proliferation when expressed in NIH3T3 or C3H10T1/2 fibroblast cell lines. The transforming cDNA encoded a protein, designated Dbs, which had a region of high sequence similarity to the Dbl proto-oncogene. This region included motifs characteristic of the CDC24 family of guanine nucleotide exchange factors, and an adjacent pleckstrin homology domain. Dbs was distinguished from Dbl by an N-terminal extension and the presence of an SH3 domain at its C terminus. Deletions of the Dbs-encoding cDNA demonstrated that transformation of NIH3T3 cells required intact exchange factor and pleckstrin homology domains, but did not require the SH3 domain. In contrast to Dbl, the N-terminal sequences of Dbs did not suppress its transforming activity. The Dbs gene was expressed at low levels in several murine hemopoietic cell lines and in thymus and spleen, and at higher levels in other tissues, particularly in brain. Dbs may be one of a large family of exchange factors which provide cell-type specific pathways for regulating proliferating via the activation of Ras-like proteins. PMID- 7862450 TI - Wild-type p53 modulates apoptosis of normal, IL-3 deprived, hematopoietic cells. AB - Apoptotic cell death is an active process which regulates the maintenance of the hematopoietic homeostasis. It has been reported that wild-type p53 (wt-p53) protein induces apoptosis in leukemia cells. To assess whether p53 is involved in the apoptotic process of normal hematopoietic cells, we introduced the temperature-sensitive p53Val135 mutant into the murine myeloid precursor cell line 32Dcl3. These are diploid, non-tumorigenic cells whose survival and proliferation are dependent upon growth factor supply (IL-3 and serum). Overexpression of wt-p53 protein does not affect morphology and proliferation of 32D cells as long as they are maintained in the presence of IL-3. However, after IL-3 withdrawal, wt-p53 overexpression significantly accelerates apoptosis. This phenomenon is IL-3 specific since no differences in death rates induced by serum starvation are found between parental cells and p53-transfectants. When the latter experiments are carried out at 37 degrees C with p53 protein in mutant conformation, an extended survival of 32D cells is observed after IL-3 deprivation, but not after serum withdrawal. Taken together, these results show that wt-p53 actively mediates the apoptosis due to the absence of specific growth factors, such as IL-3, suggesting that p53 might be involved in the response of myeloid precursors to environmental cytokines for the maintenance of the hematopoietic homeostasis. PMID- 7862451 TI - The Met/HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit. AB - The c-MET oncogene encodes the receptor for the Hepatocyte Growth Factor/Scatter Factor (HGF), a cytokine that stimulates the invasive growth of normal and neoplastic cells. The Met/HGF receptor is expressed by epithelial cells and its ligand by cells of mesenchymal origin. Receptor-ligand interaction occurs via a paracrine circuit. We studied the expression of the Met/HGF receptor and of its ligand in mesenchymal human tumours by examining 39 clinical samples of bone tumours. The Met/HGF receptor was not detectable in the majority of bone tumours, as expected from their mesenchymal origin. Notably, the receptor was overexpressed in 60% of the osteosarcomas examined. In 12 osteosarcoma cell lines the Met/HGF receptor was overexpressed, phosphorylated by HGF stimulation and fully functional. HGF was detected in two out of seven clinical specimens of osteosarcoma. The ligand and the receptor are co-expressed in two clonal osteosarcoma cell lines. In these lines the Met/HGF receptor was constitutively phosphorylated; phosphorylation was suppressed by suramin treatment, a known blocker of autocrine loops. These data suggest that activation of the Met/HGF receptor by a paracrine or an autocrine mechanism might play a role in the particularly aggressive behaviour of osteosarcomas. PMID- 7862452 TI - Cdk4 integrates growth stimulatory and inhibitory signals during G1 phase of hematopoietic cells. AB - Proliferation of hematopoietic cells is controlled by both growth stimulatory and inhibitory cytokines acting primarily in G1, but the mechanisms which integrate these disparate signals are unknown. In a myeloid cell line dependent on interleukin-3 (IL-3) for proliferation, expression of the cyclin dependent kinase Cdk4 and D-type cyclin partners, D2 and D3, in mid G1 was found to be directly related to the concentration of IL-3. TGF beta 1, which induces cell cycle arrest in mid-G1, blocked IL-3-induced expression of Cdk4, but had no effect on expression of cyclins D2 or D3. Sublines made to constitutively express Cdk4, but not lines constitutively expressing cyclins D2 or D3, were hyper responsive to IL 3 and resistant to TGF beta 1. Using an in vitro kinase assay with recombinant retinoblastoma protein (Rb) as a substrate, cyclin D2-associated kinase activity was shown to be induced in G1 by IL-3 and inhibited by TGF beta 1. Constitutive expression of Cdk4, but not cyclin D2 or D3, increased cyclin D2-associated Rb kinase activity and this activity could no longer be inhibited by TGF beta 1. Also, in vivo phosphorylation of Rb was inhibited by TGF beta 1 in wild type but not in Cdk4 lines. Cdk2 kinase activity was also decreased by TGF beta 1, and restored by overexpression of Cdk4. These results implicate Cdk4 activity as a mid G1 checkpoint sensitive to both growth stimulatory and inhibitory cytokines. PMID- 7862453 TI - The product of the NF2 tumour suppressor gene localizes near the plasma membrane and is highly expressed in muscle cells. AB - Neurofibromatosis type 2 (NF2) is a disease resulting in the formation of schwannomas of the eighth cranial nerve, and other central nervous system tumours. A tumour suppressor gene has been found to be responsible for this disorder. The 595 amino acid NF2 protein shows a great deal of homology to a superfamily of membrane organizing proteins. To generate antibodies against the NF2 protein four synthetic peptides (SP) were injected in rabbits. COS cells transfected with an NF2 cDNA construct in an expression vector were used for immunocytochemical staining experiments; lysates of transfected COS cells were used for Western blotting experiments, as were lysates of E. coli cultures transformed with an NF2 cDNA construct subcloned in a prokaryotic expression vector. In western blots all sera detected a band indicating the appropriate molecular weight in lysates of transfected COS cells and E. coli. Immunocytochemical staining experiments indicate that the NF2 protein localizes in or near the cell membrane. Immunohistochemical staining of human tissue sections demonstrated the presence of the NF2 protein in muscle-, and Schwann cells. These results support the hypothesis that the NF2 protein functions as a membrane organizing element. PMID- 7862454 TI - Autocrine mitogen IgEGF cooperates with c-myc or with the Hcs locus during hepatocarcinogenesis in transgenic mice. AB - Hepatocarcinogenesis is deterministic in transgenic mice expressing in the liver gene construct Alb-DS4 that encodes autocrine growth factor IgEGF (D Stern et al. (1987), Science 235: 321-324), causing their death within 7.1 months. Hepatic expression of construct AAT-myc encoding murine c-myc causes liver cancer in 44% of the mice at 14.8 months. Cooperation of these genes was evident in CD2F1 transgenics bearing Alb-DS4 plus AAT-myc, in which accelerated hepatocellular carcinoma (HCC) formation caused death of all mice within 4.4 months. Alb-DS4 also cooperates with the Hcs locus, which in C3H/HeJ mice mediates high susceptibility to spontaneous hepatocarcinogenesis, causing accelerated formation of HCC to which mice succumbed at 5.1 months. Thus, genes that predispose to HCC formation cooperate in transgenic mice and their interaction is a key to understand mechanisms that cause liver cancer. PMID- 7862455 TI - Differential regulation of endogenous endonuclease activation in isolated murine fibroblast nuclei by ras and bcl-2. AB - Transfection of a murine fibroblast cell line with an activated form of the Harvey ras oncogene conferred sensitivity to apoptosis induced by various agents. This intrinsic sensitivity to apoptosis correlated with the expression of endogenous endonuclease activity in isolated nuclei that was undetectable in the untransfected parental cell line. Subsequent transfection with the human bcl-2 oncogene prevented the morphological and biochemical features of apoptosis in whole cells, although it failed to confer complete protection against cell death. Furthermore, transfection of the bcl-2 oncogene also inhibited the enhanced endonuclease activity in isolated nuclei. Our results indicate that some of the effects of Ha-ras and bcl-2 and potentially other oncogenes, are exerted on the biochemical machinery of apoptosis at the level of the nucleus. PMID- 7862456 TI - Cyclin D1 oncoprotein aberrantly accumulates in malignancies of diverse histogenesis. AB - Cyclin D1 is a cell cycle regulator essential for G1 phase progression and a candidate proto-oncogene whose deregulated expression has been implicated in pathogenesis of several types of cancer. We have examined expression of cyclin D1 in 212 primary tumours of five histogenetically distinct types by immunohistochemistry and found strong aberrant accumulation of the protein in 21%, and a moderate overabundance in further 25% of cases. While the abnormalities were more frequent in carcinomas of the breast, i.e. the cancer type known for cyclin D1 gene amplification, aberrant expression was also seen in significant subsets of colorectal cancers, soft tissue sarcomas, uterine carcinomas and malignant melanomas. Comparison of distinct stages of tumour progression showed concordant cyclin D1 patterns in the in situ vs invasive breast carcinoma components (n = 37) and between primary and metastatic lesions (n = 51) of several tumour types. The specificity of the immunohistochemical data was supported by immunoblotting analysis of tissue and tumour lysates, and the tumour-specific over-expression was confirmed by computer-assisted image analysis. These observations suggest that alterations of cyclin D1 expression represent a common feature of malignancies of diverse histogenesis and indicate that both the spectrum of tumour types and the frequency of cyclin D1 aberrations significantly exceed previous estimations based on genetic analyses. PMID- 7862457 TI - Xenopus laevis p53 protein: sequence-specific DNA binding, transcriptional regulation and oligomerization are evolutionarily conserved. AB - The well conserved human and murine p53 proteins are tetramers that can activate transcription from templates bearing p53 binding sites. Since the normal function of mammalian p53 is necessary for preserving the stability of genome, we examined the properties of purified Xenopus p53 (Xp53) to determine whether it shares similar biochemical activities. Xp53 was shown to bind specifically to sites containing the p53 consensus sequence derived for human p53. Moreover, Xp53 transactivates reporter genes containing a human p53 response element in vivo. Finally, Xp53 can be cross-linked into tetramers in a manner similar to human p53. However, Xp53 forms hetero-oligomers with human or murine p53 only very ineffectively, in contrast to the efficient hetero-oligomer formation that occurs between human and murine p53 polypeptides. Taken together, our data indicate that sequence specific DNA binding, transcriptional regulation and oligomerization of p53 are common properties of vertebrate p53 proteins, and thus they are likely to be required for the biological activity of the protein. PMID- 7862458 TI - No point mutation but decreased expression of the p16/MTS1 tumor suppressor gene in nasopharyngeal carcinomas. AB - Nasopharyngeal carcinoma (NPC) is a malignancy which occurs at high incidence in southern China and southeast Asia. The molecular mechanism of this disease, however, is not well understood. Recently, a homozygous deletion and/or loss of heterozygosity on chromosome 9p21-22 was found in several primary NPCs (Huang et al., Cancer Res. 54: 4003-4006, 1994), suggesting that a potential tumor suppressor gene(s) residing in this region may play a role in nasopharyngeal carcinogenesis. Since p16/MTS1, a potential tumor suppressor gene, whose mutations/deletions are frequently found in variety of tumor cells, was mapped to chromosome 9p21, we investigated the possible involvement of this gene in the development of NPC by mutational and Northern blot analysis. SSCP-direct sequencing revealed no point mutations of the p16/MTS-1 gene in any of 42 primary NPC biopsies from three geographical regions nor in two NPC cell lines. We did, however, observe a codon 140ala-->thr polymorphism in the gene, which has been previously reported as a point mutation. Furthermore, Northern analysis revealed a decreased expression of the p16/MTS1 gene in two out of two NPC cell lines as compared with immortalized/nontransformed cell lines. These results suggest that down regulation rather than a point mutation of the p16/MTS1 gene may play a role in the genesis of NPC. PMID- 7862459 TI - p53 phosphorylation mutants retain transcription activity. AB - To investigate the effect of phosphorylation on the transcription activity of p53, ten phosphorylation mutants were constructed covering all the identified phosphorylation sites of rat p53. These included mutants of two casein kinase I sites (Ser6 and Ser9), two DNA-PK sites (Ser15 and Ser39), a p34cdc2 site (Ser313), the adjacent Ser312 and a casein kinase II site (Ser390). Two double phosphorylation mutants (Ser4, 6 and Ser15, 390) and one triple phosphorylation mutant (Ser4, 6 and 15) were also constructed. The transcription activity of all the p53 phosphorylation mutants was tested by transfection into two different types of cells, Saos-2 cells and p53(-/-) fibroblasts derived from p53 knock out mice, which both lack endogenouse p53. Surprisingly, all the p53 phosphorylation mutants retain transcription activity and the seven mutants tested can also suppress cell growth. PMID- 7862460 TI - Structure and transcription of the genomic locus encoding murine c-Mpl, a receptor for thrombopoietin. AB - We have cloned and characterised the murine gene encoding c-Mpl, a receptor for thrombopoietin and member of the hematopoietin receptor superfamily. The gene encompasses 15 kb of the mouse genome and the organisation of its 12 exons conforms closely to the pattern observed for the genes of other hematopoietin receptor family members. A site for initiation of c-mpl transcription was identified 13 nucleotides upstream of the proposed translation initiation codon. The murine mpl promoter sequence lacks conventional TATA and CAAT motifs although the transcription initiation site shares homology with the initiator sequence that specifies transcription initiation in the terminal deoxynucleotidyl transferase gene. The promoter contains consensus binding sequences for several transcriptional regulators including Ets and GATA factors, which have been implicated in control of transcription in megakaryocytes, a cell type that expresses mpl. The generation of multiple transcripts is a feature of the mpl locus. Two distinct mpl transcripts differing by an in-frame insertion of 24 nucleotides were detected in mouse spleen cells. Genomic sequence analysis identified differential splicing of alternative exon 4 sequences as the likely basis for these transcripts, which are predicted to encode receptors which differ within the first Mpl hematopoietin receptor domain. PMID- 7862461 TI - Reversion of a human tumour cell line containing oncogenic p21ras is associated with a defect in the post-translational processing of the ras protein. AB - Correct post-translational modifications of the ras proteins are essential for their membrane localisation and functioning. The flat revertant cell lines 1aCB and 8b, derived from the human bladder carcinoma cell line EJ, contain the transforming gene V12Ha-ras and are resistant to retransformation by ras protein or DNA, but still do require the presence of ras for proliferation. Both revertant cell lines demonstrated reduced levels of membrane associated p21ras when compared to their parental EJ cell lines. This reduced level in 1aCB was reflected by an increase in nuclear associated p21ras, as seen by immunofluorescence of endogenous and introduced ras. In addition, 1aCB had a reduced ratio of ras in the detergent to aqueous phases after triton X114 partitioning, suggesting a defect in Step I processing of the p21ras in the cell line. This was not however due to defects in the Step I enzymes farnesyltransferase or carboxymethyltransferase whose activities were not reduced. PMID- 7862462 TI - Heterogeneity of antigen-specific CD4+ T cell clones from a patient with Schistosomiasis mansoni. AB - Two subsets of differentiated murine helper T cells, Th1 and Th2, based on secretion products in response to antigen have been described (Cher & Mosmann 1987, Coffman et al. 1988, Lopez et al. 1988, Paliard et al. 1988, Patel et al. 1988, Mosmann & Coffman 1989). To analyse immunological function of antigen specific CD4+T cells in human schistosomiasis, we produced schistosomal egg antigen-specific T cell clones from a former patient. We identified four different types of CD4+ T cell clones by analysis of cytokine production. Two of the four types of the clones corresponded to murine Th1 or Th2 subsets; a third type was of the Th0 subset (Th1 + 2) and a fourth type produced IL-5 dissociated from IL-4. Analysis of the antigen(s) recognized by these T cell clones showed that all of the clones proliferated in response to soluble egg antigen(s) (SEA) found within a pl fraction whose pH was 5.2. T cell Western blot analysis of the stimulatory pl fraction demonstrated that the apparent Mr of the relevant antigens recognized by the clones were 38 kDa for the Th2 homologue, and 45-55 kDa for the Th1 homologue. PMID- 7862463 TI - The effect of treating with anti-interleukin-1 receptor antibody on the course of experimental murine cutaneous leishmaniasis. AB - To assess the role of interleukin-1 (IL-1) in cutaneous leishmaniasis, Leishmania major-infected mice were treated with an anti-IL-1 receptor monoclonal antibody, LA-15.6. MoAb LA-15.6 prevents binding of IL-1 to both the T cell and B cell/macrophage forms of the IL-1 receptor. We found that treating with LA 15.6 inhibited the development of cutaneous lesions of L. major in both genetically susceptible and resistant mice. Interestingly, this treatment had little or no effect on parasite numbers in the lesions or on the cytokines (interferon-gamma, interleukin-4) that the animals produced in response to infection with the parasite. These results suggest that although IL-1 plays a detrimental role in cutaneous leishmaniasis, it does not mediate this effect by altering the parasite specific T cell response. PMID- 7862464 TI - Inhibition of Plasmodium falciparum growth in vitro by CD4+ and CD8+ T cells from non-exposed donors. AB - T cells from most adult non-exposed donors, which express a memory phenotype (CD45RO+), can respond by proliferation to P. falciparum asexual stages in vitro. Such cells may have arisen from exposure to environmental organisms. To address the efficacy of such cells in eliminating parasites and investigate the mechanisms involved, we have used an in vitro assay where parasite growth can be precisely monitored in the presence of different cell preparations. Unfractionated peripheral blood mononuclear cells (PBMC) from both malaria exposed and non-exposed donors inhibited parasite growth by up to 62% in a two day assay. Purified T cells in the presence of adherent cells had a similar effect, but purified T cells alone or adherent cells alone had minimal effect. Antigens released at the time of schizont rupture were maximally effective in stimulating interferon-gamma (IFN gamma) production. Neutralizing antibodies to IFN gamma showed a partial reduction of growth inhibition in some individuals tested suggesting that different mechanisms may be operative. Neutralizing antibody to TNF alpha had a partial effect in combination with anti-IFN gamma. Antibodies to IL-1 and IL-4 had no effect. T cell fractionation experiments showed that while purified CD4+ T cells from some donors produced IFN gamma and inhibited parasite growth, purified CD8+ T cells could inhibit parasite growth to a greater extent without production of detectable IFN gamma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862465 TI - Antigen presentation by epidermal Langerhans cells in experimental cutaneous leishmaniasis. AB - Cutaneous leishmaniasis is a disease induced by intradermal injection of leishmania promastigotes. Since the first cells the parasite encounters are those of the skin, the involvement of this organ in the early immune response might be relevant to the outcome of the disease. In this study we examined the ability of epidermal langerhans cells (LC) to become infected in vivo and to function as antigen presenting cells during the early hours of infection with Leishmania major. Our experiments showed that LC from mice injected with parasites can present antigen to a leishmania-specific T cell line when LC are obtained as early as four h after infection. The stimulation was specific, since LC from leishmania injected mice did not present antigen to an ovalbumin-specific T cell line nor did LC from ovalbumin-injected mice present antigen to the leishmania specific T cell line. Despite the ability of epidermal LC cells to present antigen, no parasites were detected in the epidermis, suggesting that these cells are not directly involved in establishing an infection. PMID- 7862466 TI - Identification of a 94-kilodalton antigen on Leishmania promastigote forms and its specific recognition in human and canine visceral leishmaniasis. AB - We have analysed by immunoblotting sera from humans and dogs with visceral leishmaniasis, from the Old World as well as the New. When lysates of promastigotes are used as antigens, antibodies against a 94 kDa Leishmania component are detected, regardless of the age and geographical origin of the patient, the serum antibody titre as measured by indirect immunofluorescence, and the number of arcs in counterimmunoelectrophoresis. Low dilutions of sera from patients with Old and New World cutaneous leishmaniasis did not react with the 94 kDa antigen, whatever the species of Leishmania used as antigens. Sera from patients with other infections than leishmaniases, or without infection, are negative, even at low dilution. Anti-94 kDa antibodies were detected in the sera of Leishmania-infected dogs from both the Old and the New World. When lysates of Leishmania mexicana axenic amastigotes are used as antigens, the 94-kDa antigen was little or none identified by sera from humans and dogs with visceral leishmaniasis, and never recognized by control sera. Thus, the specific recognition of the 94-kDa promastigote antigen in human and canine visceral leishmaniasis suggests that this antigen could be a potential candidate in the differential immunodiagnosis of the disease. PMID- 7862467 TI - In-hospital mortality for surgical repair of congenital heart defects: preliminary observations of variation by hospital caseload. AB - OBJECTIVE: To examine the impact of hospital caseload on in-hospital mortality for pediatric congenital heart surgery. DESIGN: Population-based, retrospective cohort study. SETTING: Acute care hospitals in California and Massachusetts. PATIENTS: Children undergoing surgery for congenital heart disease, identified by the presence of procedure codes indicating surgical repair of a congenital heart defect in computerized statewide hospital discharge abstract databases. Cases were grouped into four categories based on the complexity of the procedure. MAIN OUTCOME MEASURES: Adjusted odds ratios (OR) for in-hospital death were estimated using generalized estimating equations that account for the intra-institutional correlation among patients. RESULTS: A total of 2833 cases at 37 centers were identified. Compared with centers performing > 300 cases per year, after controlling for patient characteristics, centers performing < 10 cases per year had an OR for in-hospital death of 7.7 (95% confidence interval (CI) [1.6-37.8]); 10 to 100 cases, OR = 2.9 (95% CI [1.6-5.3]); 101 to 300 cases, OR = 3.0 (95% CI [1.8-4.9]). Independent risk factors for mortality included procedure complexity category (P < .0001), use of cardiopulmonary bypass (P < .0001), young age at surgery (P = .001), and transfer from another acute care hospital (P < .0001). Few differences were found by hospital caseload in length of stay or total hospital charges. CONCLUSIONS: For children with a congenital heart defect who underwent surgery in California in 1988 or Massachusetts in 1989, the risk of dying in-hospital was much lower if the surgery was performed at an institution performing > 300 cases annually. This study was limited by the absence of clinical detail in discharge abstract databases. If these findings are corroborated by other studies, health care delivery strategies that direct children requiring surgical correction of congenital heart defects to high-volume centers may substantially reduce overall mortality. PMID- 7862468 TI - Vaccine information pamphlets: more information than parents want? AB - OBJECTIVE: To assess the information needs of parents regarding childhood immunizations, and their satisfaction with the Vaccine Information Pamphlets (VIPs). RESEARCH DESIGN: Verbally administered, forced-choice survey of a representative sample. SETTING: Urban teaching hospital-primary care center (N = 73), neighborhood health center (N = 75), and a suburban private practice (N = 75). PARTICIPANTS: Parents or guardians of children scheduled for routine checkups, aged 1 month to 18 years, presenting for routine health care maintenance visits. RESULTS: Of 227 parents, 223 completed the survey. Almost all (98%) had prior experience with their children's immunizations, and 7% reported a history of a "bad" experience. Most parents stated that it was "very important" to receive information about immunizations regarding: diseases prevented by the immunizations (89%); common side effects (91%); serious side effects (89%); contraindications (91%). Eighty percent of parents indicated they wanted immunization information discussed with each vaccination. Forty-three percent of the parents were familiar with the VIPs; of these, 88% reported that the amount of information was "just right," and 94% thought the VIPs were helpful. However, 29% thought the VIPs were either too long, or somewhat too long. CONCLUSIONS: Parents indicate that they want information about many aspects of immunizations, and those familiar with the VIPs report high levels of satisfaction with the pamphlets. PMID- 7862469 TI - The use of oral transmucosal fentanyl citrate for painful procedures in children. AB - OBJECTIVE: To investigate the efficacy and safety of oral transmucosal fentanyl (OTFC) in providing analgesia and sedation for painful diagnostic procedures in children. DESIGN: Randomized, placebo-controlled clinical trial. METHOD: Forty eight children referred to the University Connecticut Division of Pediatric Hematology/Oncology for bone marrow aspiration or lumbar puncture were randomized to receive either OTFC (15 to 20 micrograms/kg) or a placebo lollipop. Thirty minutes after administration, the procedure was begun. An anesthesiologist monitored the child's heart rate, blood pressure, and oxygen saturation every 10 minutes. At the conclusion of the procedure, the nurse, the child's parent, and all children over 8 years of age were asked to rate the pain associated with the procedure using a 1 to 10 visual analogue scale. Young children (less than 8) used a modified scale, the Oucher, yielding a 0 to 5 score. RESULTS: Significant differences in pain ratings between the OTFC and placebo groups were noted on the pain scores of the parents (P = .005), nurses (P = .001), younger children (P = .006), and older children (P = .013), and median pain scores in the OTFC group were reduced to tolerable levels. Vomiting (P = .003) and itching (P = .001) were more common in the OTFC group, but no clinically significant vital sign deviations occurred. CONCLUSION: OTFC is safe and effective for use in relieving the pain of pediatric procedures, but frequency of vomiting may restrict its clinical usefulness. PMID- 7862470 TI - Carbohydrate absorption from fruit juice in young children. AB - OBJECTIVE: To compare carbohydrate absorption following ingestion of apple juice and white grape juice in 28 healthy children. DESIGN: Randomized, double-blind crossover study. SETTING: Outpatient pediatric clinic at Maimonides Medical Center. PARTICIPANTS: A total of 18 healthy infants (mean age 6.3 months) and 10 toddlers (mean age 18.0 months), representing those ages when juice is first introduced (6 months) and when juice comprises a large portion of the diet (18 months). METHODS: Breath hydrogen (H2) testing was performed after age-specific servings of white grape juice or apple juice, 4 and 8 ounces respectively, were consumed. These portions provided approximately 1 g of fructose per kg of body weight. Breath H2 responses of > 20 ppm were considered positive, indicating incomplete absorption of fruit juice carbohydrates. RESULTS: In the combined age groups, carbohydrate malabsorption occurred more frequently after apple juice consumption (54%) than after white grape juice (19%; P < .001). Significant differences in area under the breath H2 curve (AUC) were also found between the two juices in both age groups. Among toddlers, the differences between the mean peak breath H2 responses were significant (48 ppm after apple juice consumption compared with 12 ppm after white grape juice; P < .001). These differences were not significant in the infant group. Significant differences (P < .05) were seen between the two age groups after consumption of apple juice; the toddlers exhibited a greater number of positive breath H2 responses and higher peak responses compared with the infants. Data from the children who drank both juices showed significant differences in peak breath H2 responses after consumption of apple juice compared with white grape juice (P < .005). CONCLUSIONS: The study demonstrated less carbohydrate malabsorption following ingestion of white grape juice compared with apple juice in healthy 6- and 18-month-old children. PMID- 7862471 TI - The use of cranial CT scans in the triage of pediatric patients with mild head injury. AB - OBJECTIVE: Recent evidence suggests that patients with a normal cranial CT scan after head injury can be safely discharged home from the emergency department. However, supporting data from previous studies has relied on incomplete patient follow-up. We utilized a statewide comprehensive hospital abstract reporting system (CHARS) to assess whether children with normal CT scans after head injury subsequently developed intracranial sequelae in the month following their initial injury. DESIGN: Retrospective case-series study, with comprehensive statewide follow-up for 1 month. SETTING: The emergency department of a Level 1 Trauma Center in Seattle, Washington. PARTICIPANTS: All children (n = 400) with head injury, Glasgow Coma Score of 13 to 15, and initial normal CT scan seen over a 4.5-year time period. All were matched against CHARS to evaluate admissions within 30 days after emergency department disposition. For readmissions, International Classification of Diseases (9th revision) discharge and procedure information was collected. All children were also matched against the state death files. RESULTS: Four children were readmitted for neurologic reasons within 1 month following injury. One child on coumadin for heart disease developed a symptomatic subdural hematoma 5 days after head injury, requiring neurosurgical drainage. One child developed a symptomatic hemorrhagic contusion 3 days after injury, requiring observation only. Two children were readmitted 1 day after injury for concussive symptoms; both were discharged home after observation only. There were no deaths among the study population. CONCLUSIONS: Among children with a normal cranial CT scan after mild head injury, delayed intracranial sequelae requiring intervention are extremely uncommon. In otherwise stable patients, a normal cranial CT scan can identify patients to be safely discharged from the emergency department, and would be more cost-effective than 1 to 2 days of hospital observation. PMID- 7862472 TI - The surprisingly high acceptability of low-efficacy vaccines for otitis media: a survey of parents using hypothetical scenarios. AB - OBJECTIVE: To determine parental thresholds for accepting vaccines for otitis media prevention given tradeoffs of efficacy, adverse effects, and administration mode. METHOD: We interviewed 601 randomly selected parents with children 0 through 6 years of age presenting to our community pediatric clinic. For each of five hypothetical vaccines, which varied administration mode from nasal spray to two injections and adverse effects from mild to severe, parents indicated the lowest number of otitis media episodes that the vaccine had to prevent in the next 6 months for them to accept the vaccine. RESULTS: About half the parents would accept any one of the vaccines if it would prevent three or more infections in the next 6 months. When the vaccine would prevent one episode of otitis media over the next 6 months, 33% of parents would accept the medial vaccine (one injection in the thigh, with some children getting a red, sore injection site and a few having a fever of < or = 102 degrees F for one day). Seventeen percent accepted a vaccine requiring two injections (influenza vaccine-like) or having increased adverse effects (pneumococcal vaccine-like) despite the vaccine only preventing one episode of otitis media over the next 6 months. No substantial differences in these proportions were found when compared among groups by reason for-visit, recent occurrence of otitis media, or a history of recurrent otitis media in a sibling. CONCLUSION: Many parents will accept low efficacy vaccines for otitis media prevention. Parental acceptance does not vary with the child's otitis media experience but does vary with severity of adverse effects and administration mode of the vaccine. PMID- 7862473 TI - Pediatric adenoidal hypertrophy and nasal airway obstruction: reduction with aqueous nasal beclomethasone. AB - OBJECTIVE: Pediatric adenoidal obstruction of the nasal airway is associated with significant morbidity and is a frequent indication for surgery. Because efficacious medical alternatives to adenoidectomy are lacking, we assessed the potency of standard-dose topical nasal beclomethasone in reduction of adenoidal obstruction of the nasal airway. METHODS: Seventeen children, 5 to 11 years of age, exhibiting chronic obstructive nasal symptoms and a group mean (+/- SE) adenoid/choana ratio of 91 +/- 1% on rhinoscopic examination, completed an 8 week, double-blind, placebo-controlled crossover study of standard-dose aqueous nasal beclomethasone (total 336 micrograms/day) in the treatment of adenoidal hypertrophy. In a 16-week, open-label, follow-on study, subjects received beclomethasone 1 spray in each nostril twice daily (168 micrograms/day). RESULTS: Over the initial 4 weeks, improvements in the mean adenoidal obstruction of the choanae were significantly greater in the group receiving beclomethasone than in the group receiving placebo (right, -14.0% vs. +0.4%, P = .0002) (left, -15.0% vs. -2.0%, P = .0006). In the subsequent crossover 4 weeks, a significant beclomethasone carryover effect resulted in further adenoid size reduction in both treatment groups. All patients demonstrated a decrease in adenoid size with beclomethasone treatment, compared with a mixed response to placebo. Over the full 8-week crossover study, the mean (+/- SE) obstructive symptom score after beclomethasone treatment (20.5 +/- 3.0) was significantly improved compared to patients' initial (43.1 +/- 2.9) and placebo scores (31.1 +/- 4.2, P < or = .05), despite the active drug carryover effect into the placebo treatment period. Significant improvements in adenoidal obstruction and symptom scores over the 8 week crossover study were enhanced in the subsequent 16-week open-label period (P = .0001). By 24 weeks, an 82% reduction in group mean nasal obstruction symptom score accompanied a 29% mean reduction in adenoid/choana ratio. No clinical or demographic characteristic predicted a patient's degree of response to treatment. CONCLUSIONS: Properly administered aqueous nasal beclomethasone in standard doses can significantly reduce adenoidal hypertrophy and nasal airway obstructive symptoms in children. PMID- 7862474 TI - Effects of prenatal and infancy nurse home visitation on surveillance of child maltreatment. AB - OBJECTIVE: To examine the effects of prenatal and infancy nurse home visitation on the surveillance of child abuse and neglect by examining differences in the health, living conditions, and maltreatment characteristics of nurse-visited and comparison children who had been identified as maltreated in the first 4 years of life. DESIGN: Randomized controlled trial. SETTING: Carried out in a semirural community in upstate, New York. Families dispersed throughout 14 other states during 2-year period after children's second birthdays. PARTICIPANTS: 400 primiparous women registered before 30th week of pregnancy, 85% of whom were either teenaged (< 18 years at registration), unmarried, or from Hollingshead social class IV or V. Maltreated subsample consisted of 56 families in which children had a state-verified report of child abuse or neglect during the first 4 years of the children's life. INTERVENTION: Nurse home visitation from pregnancy through the second year of the child's life. MAIN RESULTS: During the two-year period after the program ended, nurse-visited maltreated children lived in homes with fewer observed safety hazards for children; their homes contained more intellectually stimulating toys, games, and reading materials; their mothers were less controlling; and the children paid 87% fewer visits to the physician for injuries or ingestions, and 38% fewer visits to the emergency department. CONCLUSIONS: Children who were identified as maltreated and who were visited by nurses during pregnancy and the first two years of life had less serious expressions of caregiving dysfunction. This is likely to be a reflection, in part, of earlier and more comprehensive detection of child maltreatment on the part of nurse-visited families. PMID- 7862475 TI - The diagnostic utility of bronchoalveolar lavage in immunocompetent children with unexplained infiltrates on chest radiograph. AB - OBJECTIVE: To assess the diagnostic utility of bronchoalveolar lavage (BAL) in a heterogeneous group of immunocompetent children with unexplained infiltrates on chest radiograph. DESIGN: This was a retrospective case series. SETTING: The setting was a tertiary care referral center in an urban children's hospital. PATIENTS: Twenty-five consecutive children, median age 4 years 6 months, had flexible bronchoscopy with BAL. Preprocedure diagnoses were right middle-lobe syndrome (3 patients), granulomatous lung disease (3 patients), adult respiratory distress syndrome (3 patients), and persistent infiltrate on chest x-ray (16 patients). The majority of patients were receiving parenteral antibiotics before bronchoscopy. BAL fluid was sent for bacterial, viral, fungal, and, if indicated, mycobacterial cultures. RESULTS: Twenty-seven procedures were performed in 25 patients. A specific diagnosis was made in eight (30%) of the procedures. Four patients had viral infections, two had fungal infections, one had a bacterial infection, and one had a mixed fungal and bacterial infection. CONCLUSION: Submitting BAL fluid for bacterial, viral, and fungal culture can be helpful in diagnosing infection in immunocompetent children. Empiric antibiotic therapy remains the standard treatment for pneumonia in children. Bronchoalveolar lavage may yield a diagnosis in patients unresponsive to empiric antibiotics. Careful selection of patients, a bronchoscopist skilled in the procedure, and the risk/benefit ratio all must be considered. PMID- 7862476 TI - Cost implications of event recordings in apnea/bradycardia home monitoring: a theoretical analysis. AB - OBJECTIVES: To evaluate the financial impact of incorporating event recordings as an integral component of home apnea/bradycardia monitoring. STUDY DESIGN: This theoretical analysis examines the cost of home monitoring when medical decisions are based on an evaluation of the cardiorespiratory waveforms surrounding each apnea/bradycardia monitor alarm (documented monitoring) compared to those based on parental observations. Data for both approaches were obtained from 155 infants referred within the first 10 days of life, because a sibling died of sudden infant death syndrome. All were followed on an impedance type apnea/bradycardia monitor with an attached event recorder. The monitor settings were 20 seconds for apnea and 80 beats per minute (bpm) for bradycardia. Parents were taught how to use the equipment, resuscitative techniques, and to complete an alarm log. The clinical protocol provided for home monitoring until there were no "episodes" (prolonged apnea or prolonged bradycardia) for 16 consecutive weeks. A polysomnogram would be obtained if an "episode" occurred. For each infant two independent approaches were used to judge the occurrence of an "episode": (1) parental report of an apnea alarm occurring during sleep or a physiologic alarm associated with skin color change or resuscitative intervention and (2) apnea > or = 20 seconds long or bradycardia > or = 10 seconds. The cost was calculated assuming a 4-week monitor rental fee of $350, a 4-week waveform interpretation fee of $180, and a $600 fee for performing and interpreting a polysomnogram. RESULTS: Episodes defined from an interpretation of the cardiorespiratory waveforms resulted in fewer diagnostic studies, a shorter period of home monitoring, and lower per patient treatment costs. CONCLUSION: Despite the increased monthly cost, incorporating event recordings as an integral component of home monitoring resulted in a lower average per patient cost. PMID- 7862477 TI - Supplementary carrying compared with advice to increase responsive parenting as interventions to prevent persistent infant crying. AB - OBJECTIVE: To compare two interventions (supplementary carrying, increased parental responsiveness) introduced from birth for their effectiveness in reducing the amounts of crying in general community infants at 2, 6, and 12 weeks age. DESIGN AND PARTICIPANTS: Mothers and infants in newborn wards of maternity hospitals were assigned to carrying intervention, responsiveness intervention, or control groups. Follow-up measures were used to confirm that the interventions were implemented and to determine their effects on infant crying. SETTING AND MEASUREMENTS: Diary measurements completed in the home were employed to measure the aspects of parental behavior targeted by the interventions. Audio recordings, diaries, and questionnaires assessed the amounts the infants cried and the impact of the crying on their mothers and the health services. Sample sizes at 6 weeks of age were 59 (carrying intervention), 57 (responsiveness intervention), and 94 infants (control group). RESULTS: The carrying intervention successfully increased the amounts the infants were carried, particularly while settled, to the target levels. The responsiveness intervention led to more limited increases in carrying and to a modest increase in feeding frequency, but did not affect measures of parental interactiveness and play. No differences in amounts of crying and fussing were found between the three groups of infants on any of the measures. Subsidiary analyses confirmed that the dependent variable (infant fuss/crying) and main independent variable (carrying while settled) were not significantly correlated. CONCLUSION: It is not, at present, possible to recommend either supplementary carrying or increased parental responsiveness as primary, preventative interventions to reduce infant crying. PMID- 7862478 TI - Quality of care for preschool children with asthma: the role of social factors and practice setting. AB - OBJECTIVE: To determine whether patient race or source of payment is associated with differences in the quality of inpatient and outpatient treatment for young children with asthma. DESIGN: Structured medical record review. SETTING: Tertiary care pediatric hospital. PATIENTS: We studied 354 patients aged 1 to 6 years discharged with asthma between October 1, 1989 and September 30, 1990. MEASURES: We developed indicators of the quality of asthma care provided before and during hospitalization and planned after discharge. Outpatient indicators were the use of inhaled beta-agonists and the use of preventive anti-inflammatory medications (inhaled steroids or cromolyn sodium) before admission. In-hospital indicators were the intensity of inhaled beta-agonist therapy in the emergency department and length of stay. Planning for post-hospital care was assessed by the prescription of a nebulizer for home use. We examined associations between these indicators and patient race and source of payment, and explored the influence of primary-care practice type on these associations. RESULTS: After adjustment for potential confounders, we found that Hispanic patients were less likely than white patients to have taken inhaled beta-agonists before admission. Both black and Hispanic patients were less likely than white patients to have taken anti inflammatory medications. When we adjusted for the patients' primary-care practice type, the effect of patient race did not persist for these indicators of outpatient care. We found no differences by patient race in emergency department care or length of hospital stay. However, black and Hispanic patients were much less likely to be prescribed a nebulizer for home use upon discharge. After adjustment for confounders, there were no differences in the quality of asthma care by source of payment. CONCLUSIONS: We found that young children of racial minorities admitted for an asthma exacerbation were less likely to have received maximally effective preventive therapy. We also identified marked differences in the quality of care planned after hospital discharge for black and Hispanic patients, compared with white patients. Particularly in an era of health reform, attention should focus on barriers to high-quality care for underserved children, who are already at high risk for asthma-related morbidity. PMID- 7862479 TI - Evaluation of an end-tidal CO2 detector during pediatric cardiopulmonary resuscitation. AB - OBJECTIVE: To determine the utility of a disposable colorimetric end-tidal CO2 detector during pediatric cardiopulmonary resuscitation (CPR) for (1) confirming endotracheal tube (ETT) position, and (2) assessing the relationship between end tidal CO2 recorded by this method and outcome of pediatric CPR. DESIGN/SETTING: Prospective observations during CPR in a university children's hospital. PARTICIPANTS: Forty children (28 male, 12 female) aged 1 week to 10 years (25 children aged < or = 1 year, mean age 27.2 months, median 7 months), weighing 2.5 to 40 kg (31 children weighing < or = 15 kg, mean 10.94 kg, median 7 kg) who underwent a total of 48 endotracheal intubations during CPR. METHODS: After intubation, ETT position was verified by usual clinical methods including direct visualization. The device was attached between the ETT and ventilation bag, the patient was manually ventilated, and a first reading was obtained. Any color change from purple (Area A, end-tidal CO2 < 0.5%) to tan or yellow (Area B or C, end-tidal CO2 > or = 0.5%) was considered to be positive for airway intubation. CPR was conducted as per Pediatric Advanced Life Support guidelines. A second reading was obtained when the decision to discontinue CPR was made. RESULTS: All nine esophageal tube positions were correctly identified by the detector. Thirty three of 39 tracheal tube positions were correctly identified (P < .001). For verifying ETT position, the device had a sensitivity of 84.6%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 60%. Readings were obtained at the end of CPR in 25 patients. All 13 patients who regained spontaneous circulation and survived to ICU admission had a second reading in the C range, while none of the 12 patients with a second reading in the A or B range survived. Both the first and second end-tidal CO2 readings in the C range correlated significantly with short-term survival (P = .01 and P < .001, respectively). Two patients were eventually discharged from the hospital. CONCLUSIONS: During CPR a positive test confirms placement of the ETT within the airway, whereas a negative test indicates either esophageal intubation or airway intubation with poor or absent pulmonary blood flow and requires an alternate means of confirmation of tube position. The detector may be of prognostic value for return of spontaneous circulation and short-term survival. PMID- 7862480 TI - Predictors of failure of high-frequency oscillatory ventilation in term infants with severe respiratory failure. AB - OBJECTIVE: To identify clinical factors in term neonates with severe respiratory failure that predict which neonates are unlikely to respond to high-frequency oscillatory ventilation (HFOV). DESIGN: This was a retrospective review of patient charts and medical records. PATIENTS: We studied 190 newborns treated with HFOV between July 1985 and December 1992. All patients were at least 35 weeks' estimated gestational age and had severe respiratory failure, defined as arterial to alveolar oxygen ratio (a/A ratio) of less than 0.2 or the need for peak inspiratory pressure greater than 35 cm H2O on conventional ventilation. RESULTS: Of the 190 patients, 111 (58%) responded to HFOV (HFOV responders), and 79 (42%) were placed on extracorporeal membrane oxygenation (ECMO) after HFOV failed to improve gas exchange (nonresponders). The two groups were similar in gender and birth weight. Factors associated with failure of HFOV to produce a sustained improvement in gas exchange were a diagnosis of congenital diaphragmatic hernia and more severe respiratory compromise as assessed by admission blood gas. Stepwise logistic regression analysis showed that a diagnosis of congenital diaphragmatic hernia/lung hypoplasia (CDH/LH) and the a/A ratio at initiation of and after 6 hours of HFOV were the only significant independent predictors of the need for ECMO. Among all the patients, the presence of CDH/LH or an initial a/A ratio of 0.05 or lower yielded a sensitivity of 74% and specificity of 77% in correctly identifying neonates in whom HFOV failed to produce a sustained improvement in oxygenation. When neonates with CDH/LH were excluded from analysis, the most significant predictor of failure of HFOV was the a/A ratio after 6 hours of HFOV. In neonates without CHD/LH, a 6-hour a/A ratio of 0.08 or lower discriminated responders from nonresponders (ie, treatment with ECMO) with a sensitivity of 77% and specificity of 92%. CONCLUSIONS: In our patients, the presence of CDH/LH, severe respiratory failure (a/A ratio 0.05 or lower) at initiation of HFOV, and lack of improvement in oxygenation (a/A ratio 0.08 or lower after 6 hours of HFOV) were associated with failure of HFOV and treatment with ECMO. This information should help other centers to identify neonates who are at the greatest risk for requiring ECMO support and thus allow prompt transfer to an ECMO center. PMID- 7862481 TI - Driveway-related child pedestrian injuries: a case-control study. AB - OBJECTIVES: To examine risk factors for driveway-related child pedestrian injuries. DESIGN: A community based case-control study. SETTING: The Auckland region of New Zealand. PARTICIPANTS: Cases (n = 53) were children killed or hospitalized as a result of a driveway-related pedestrian injury, in the Auckland region over a period of 2 years and 2 months. Controls (n = 159) were an age matched random sample of the child population of the Auckland region. RESULTS: The absence of physical separation of the driveway from the children's play area was associated with a threefold increase in the risk of driveway-related child pedestrian injury (OR = 3.50; 95% CI 1.38, 8.92). Children living in homes with shared driveways were also at significantly increased risk (OR = 3.24; 95% CI 1.22, 8.63). The population attributable risk associated with the absence of physical separation of the driveway from the children's play area was 50.0% (95% CI 24.7, 75.3). CONCLUSION: The fencing of residential driveways as a strategy for the prevention of driveway-related child pedestrian injuries deserves further attention. PMID- 7862482 TI - Myelin in SIDS: assessment of development and damage using MRI. AB - OBJECTIVE: Abnormalities of myelin that have been reported in Sudden Infant Death Syndrome (SIDS) include a delay in development and focal lesions presumed to be secondary to hypoxia. Magnetic resonance imaging (MRI) gives excellent images of white matter and can be used to map the progress of myelination and to demonstrate focal lesions. It was the aim of this study to determine whether any MRI abnormality of myelin could be detected in the brains of SIDS compared to control infants. METHODS: The brains of 28 SIDS and 14 control infants were fixed in formalin and scanned with MRI. The proton density, T2-weighted, and inversion recovery scans were assessed for the presence of focal white matter lesions. The amount of myelin in 26 sites was measured in the proton density scans, using a densitometer. The amount of myelin present could be assessed in 21 of 26 sites. RESULTS: In 15 of 21 sites the amount of myelin for age was the same in SIDS and controls. In three sites the rate of myelination was greater in SIDS than control and in another three sites the amount of myelin for age was greater in SIDS than control infants, but these differences were not seen in infants aged less than 8 months. No focal abnormalities of white matter were seen in either SIDS or control infants. CONCLUSIONS: The development of white matter in brains of SIDS infants less than 8 months old is the same as in controls, and in older SIDS infants white matter development may be slightly advanced compared to controls. No hypoxic changes can be seen in SIDS white matter on MRI. PMID- 7862483 TI - Bacillus Calmette-Guerin complications in children born to HIV-1-infected women with a review of the literature. AB - OBJECTIVE: To compare the risk of complications following Bacillus Calmette Guerin (BCG) vaccination among children by maternal and infant HIV-1 infection status as part of an investigation of an outbreak of BCG complications. METHODS: A nonconcurrent cohort study of BCG complications among 125 infants born to HIV-1 seropositive and 166 infants born to HIV-1 seronegative mothers was conducted in Cite Soleil, Haiti. Infants were examined at regular intervals until 15 months of age, and complications from BCG were documented. An investigation of BCG vaccination practices was conducted. RESULTS: Mild or moderate complications occurred among 16 of 166 (9.6%) infants born to HIV-1 seronegative mothers compared with 4 of 13 HIV-1-infected infants (30.8%, P = .04) and 10 of 75 (13.3%, P = .39) uninfected infants born to HIV-1-infected mothers. No serious complications were noted. The outbreak of complications was associated with administration of 2.0 to 2.5 times the recommended dose of BCG vaccine. CONCLUSIONS: This and five other cohort studies indicate that there may be a small increased risk of complications following BCG vaccination among HIV-1 infected children, but the reactions are usually mild and the risk does not outweigh the benefits of BCG vaccination in populations at high risk of tuberculosis during infancy and childhood. PMID- 7862484 TI - Hockey helmets, face masks, and injurious behavior. AB - OBJECTIVE: To educate physicians about factors that contribute to injurious behaviors in ice hockey and to propose that the medical community play a role in advocating change within the sport. METHODS: A review of relevant literature on the topic was conducted, with information drawn from scientific journal publications, conference proceeding, theses, and newspaper publications. RESULTS: The introduction of mandatory head and facial protection has been effective in virtually eliminating ocular, facial, and dental injuries in youth hockey, but it has also been problematically linked with an increase in catastrophic spinal injuries. Players adopt a false sense of security when donning the equipment, leading them to take excessive and unwarranted risks because of the protection they are supposedly afforded. The addition of these protective devices has also altered how officials perceive game situations, leading them to be more lenient in administering penalties. The net result has been an increase in illegal and injurious behaviors, such as checking from behind. CONCLUSION: Physician advocacy may play an important role in effecting change within the sport. PMID- 7862485 TI - The Ambulatory Pediatric Association. PMID- 7862486 TI - Do we need the term "FAE"? PMID- 7862487 TI - Sudden infant death syndrome and subsequent siblings. CHIME Steering Committee. Collaborative Home Infants Monitoring Evaluation. PMID- 7862488 TI - Use of fruit juice in the diets of young children. PMID- 7862489 TI - Iodine-induced hyperthyroidism in a newborn. PMID- 7862490 TI - Alcohol use and abuse: a pediatric concern. American Academy of Pediatrics Committee on Substance Abuse. PMID- 7862491 TI - Health supervision for children with achondroplasia. American Academy of Pediatrics Committee on Genetics. PMID- 7862492 TI - "110- buzz number". PMID- 7862493 TI - Antenatal formula advertising. PMID- 7862494 TI - Resuscitation of neonates with the laryngeal mask airway--a caution. PMID- 7862495 TI - Child abuse law. PMID- 7862496 TI - "Topical steroid holiday". PMID- 7862497 TI - Ichthyosis is not transmitted through skin ointment. PMID- 7862498 TI - Acquaintance rape. AB - The author examines how culturally learned sex roles and myths about rape come together to give acquaintance rape a status somewhere between accepted practice and unacceptable crime. Risk factors, barriers to reporting rape, and factors that make college students a vulnerable group, are discussed. Institutional programs and resources are highlighted, along with a new educational approach using small group workshops. PMID- 7862499 TI - Clara's story: post-traumatic response and therapeutic art. AB - Post-traumatic response (PTR) is a reaction to a distressful event or events. PTR can be immediate, delayed, or chronic. Delayed or chronic PTR is often observed in adults who experienced repeated episodes of childhood physical, emotional, and/or sexual abuse. After years of secrecy, fear, denial, repression, suppression, and/or maladaptive coping patterns, recovery for chronic survivors can be lengthy, painful, and arduous. Recovery work can be facilitated by a therapeutic approach combining cognitive and expressive techniques. A case study illustrates one client's four-year recovery period. PMID- 7862500 TI - Self-reported experiences of physical and sexual abuse among runaway youths. AB - The authors provide data in this descriptive study to suggest that physical and sexual abuse within the family system frequently expedites youths' decisions to leave home. The role that drugs and alcohol play in runaway youths' lifestyles is also explained. PMID- 7862501 TI - Depression as a function of expressiveness/instrumentality among nurses. AB - In this study the author investigated the relationship of depression to sex role orientation in women employed in a traditional female occupation. The specific purpose of the study was to assess whether women employed in nursing would be more likely to be expressive (feminine/sex typed) in their sex role orientation and to evaluate the degree of depression among women with high levels of expressive (feminine/sex-typed) characteristics. Results supported the hypothesis that nurses who subscribed to a traditional feminine role (feminine sex typing) had a greater vulnerability to depression. However, their rate of depression was significantly less than that found among women in general. PMID- 7862502 TI - Poverty and health care: compassion or dispassion? PMID- 7862503 TI - On paradox in nursing. PMID- 7862504 TI - Washington update. PMID- 7862505 TI - The new Russian law on psychiatric care. AB - On July 2, 1992, President Boris Yeltsin signed into effect a law that has the potential for advancing human rights of psychiatric clients in the Russian Federation. The author provides a comparative analysis of the U.S. and Russian psychiatric laws, demonstrating a striking similarity of the laws in terms of substance and scope. PMID- 7862506 TI - Schizophrenia and expressed emotion. AB - Research on expressed emotion (EE) is considered in the historical context of writings about disturbed family communication patterns and schizophrenia. More recent findings about the interaction between EE and schizophrenic relapse and the relevance of these findings for both clients and their relatives/carers are also summarized. The author offers recommendations for developing programs that focus on the client's social skills deficits. PMID- 7862507 TI - The parallel process in clinical supervision with a schizophrenic client. AB - The authors analyze a male nurse's account of how he experienced his interaction with a female schizophrenic client during sessions of systematic clinical supervision. Notes taken during 15 sessions were analyzed by means of open coding. The analysis revealed the importance of being aware of the parallel process that occurs among the client, the primary nurse, and the unit staff. PMID- 7862509 TI - The paradox of growth and decay. PMID- 7862508 TI - Our global community. PMID- 7862510 TI - Caring: the rediscovery of our nursing roots. PMID- 7862511 TI - A holistic-existential model for psychiatric nursing. AB - The authors offer a holistic model for psychiatric nursing based on a existential concept of man. They assert that the biomedical model of health and sickness is not sufficient to understand the reality in which psychiatric nurses practice. Within this model, understanding clients in relation to their life contexts becomes the focus, as well as trying to comprehend what effects suffering has on their ability to function. The relationship between nurse and client is discussed from a point of view that considers central existential precepts, such as: equality, encounter/being present, self-esteem/significance, responsibility and choice, objectives, meaning and clarification of values, guilt and atonement, openness and insight, conformity versus rebellion and finally hope. PMID- 7862512 TI - A group for "wandering" institutionalized clients with primary degenerative dementia. AB - The authors implemented a group in a state psychiatric institution for women with primary degeneration dementia. The group provided scheduled opportunity in a nonrestrictive environment for structured movement and sensory stimulation. Over a period of nine sessions, small but significant changes were noted in the members' behavior. This type of therapy can benefit such limited clients by enhancing the quality of their life in the institution. PMID- 7862513 TI - Anger management using cognitive group therapy. AB - Cognitive therapy has been applied to the treatment of various psychosocial phenomena, including anger. Yet, the literature contains no reference to applying these concepts within a group setting. Using the basic premises of cognitive and group therapies, the author discusses anger arousal and anger management using a cognitive model in a group therapy setting. PMID- 7862514 TI - Psychiatric mental health nursing in a biopsychosocial era. AB - Clients in long-term facilities carry a wide array of psychiatric diagnoses, often with equally diverse medical problems. This "back ward" population requires a specialized area of psychiatric mental health nursing practice. The need for comprehensive assessment and adequate interventions, and the various frustrations of nursing staff, are discussed using a case example. PMID- 7862515 TI - Implementing an inpatient eating disorders program. AB - Inpatient treatment can be quite effective for clients with severe or persistent eating disorders. A successful treatment program, however, requires extensive nursing participation. The author addresses specific clinical problems and system issues related to this population of clients. She stresses the importance of clinical expertise among nursing staff and coordination with interdisciplinary staff members. PMID- 7862516 TI - Can nursing have its own theory of ethics? PMID- 7862517 TI - Dealing with resistance in group therapy. AB - Client resistance to psychotherapeutic efforts often has a demoralizing effect on the nurse therapist, especially when the resistance crops up in a group therapy setting. As the therapist becomes more experienced with handling resistance, it becomes less threatening. Ironically, resistance signals that treatment is progressing--that the therapist and the group members are getting close to crucial issues. The author provides an overview of predominant forms of resistance and frameworks for effective clinical management. PMID- 7862518 TI - Curing vs. caring: a blessing or a curse? PMID- 7862519 TI - Principles of a therapeutic milieu: an overview. AB - The author provides a concise overview of how the milieu functions of structure, involvement, containment, support, and validation can be used to create a positive treatment environment. Examples of an unhealthy milieu are contrasted with these therapeutic principles. PMID- 7862520 TI - Group remotivation therapy for the 90s. AB - The authors assert that some of the most regressed, treatment-resistant clients with persistent mental illness will show a favorable response to a group approach called remotivation therapy. The remotivation therapy techniques of the 1950s have been updated by psychiatric nurses and a social work clinician in one VA setting. The authors assert that remotivation therapy approaches are easy to implement, personally rewarding, and effective in promoting interaction in such clients. PMID- 7862521 TI - Human ribosomal protein L7 inhibits cell-free translation in reticulocyte lysates and affects the expression of nuclear proteins upon stable transfection into Jurkat T-lymphoma cells. AB - Eucaryotic ribosomal protein L7 carries a 'Basic-Region-Leucine-Zipper (BZIP)' like region which mediates high-affinity binding to mRNA and 28S rRNA and formation of homodimers [P. Hemmerich et al. (1993) Nucleic Acids Res. 21, 223 231). Its biological function is unknown as yet and no direct L7-equivalent in procaryotes has been found. In this report we show that eucaryotic L7 specifically inhibits the cell-free translation of reporter mRNAs. The interaction of L7 with mRNA is an essential step in this reaction which is inhibitable by antibodies directed against the BZIP-like region of L7, and by competitors of mRNA binding. L7-mediated inhibition of cell-free translation of polyA+ RNA from Jurkat T-lymphoma cells is selective in that the synthesis of a major 46 kD protein is suppressed. Upon stable transfection of L7 cDNA into Jurkat lymphoma cells two major proteins disappear, namely one nuclear protein and one which associates with the nucleus. Our data suggest a regulatory role of protein L7 in the eucaryotic translation apparatus. PMID- 7862522 TI - The fission yeast gene pmt1+ encodes a DNA methyltransferase homologue. AB - DNA methylation of cytosine residues is a widespread phenomenon and has been implicated in a number of biological processes in both prokaryotes and eukaryotes. This methylation occurs at the 5-position of cytosine and is catalyzed by a distinct family of conserved enzymes, the cytosine-5 methyltransferases (m5C-MTases). We have cloned a fission yeast gene pmt1+ (pombe methyltransferase) which encodes a protein that shares significant homology with both prokaryotic and eukaryotic m5C-MTases. All 10 conserved domains found in these enzymes are present in the pmt1 protein. This is the first m5C-MTase homologue cloned from a fungal species. Its presence is surprising, given the inability to detect DNA methylation in yeasts. Haploid cells lacking the pmt1+ gene are viable, indicating that pmt1+ is not an essential gene. Purified, bacterially produced pmt1 protein does not possess obvious methyltransferase activity in vitro. Thus the biological significance of the m5C-MTase homologue in fission yeast is currently unclear. PMID- 7862523 TI - Probing the molecular mechanism of action of co-repressor in the E. coli methionine repressor-operator complex using surface plasmon resonance (SPR). AB - We have studied quantitatively the effect of the corepressor, S adenosylmethionine (SAM), on the interaction between the E. coli methionine repressor, MetJ, and an idealised operator fragment, by recording measurements of surface plasmon resonance using a BIAcore instrument. We have recorded kinetic binding data in the presence of SAM, which carries a net positive charge, and two corepressor analogues, adenosylornithine (AO) and aza-SAM, which differ in the location of the atom carrying the positive charge. Our data support the hypothesis that the effect of the corepressor is electrostatic in origin. The difference in electrostatic interaction energy between the SAM- and AO-repressor operator complexes of approximately 3.5 kJ/mol calculated from the known three dimensional structure is within the range of our experimentally determined values of 2.8-4.3 kJ/mol. These results illustrate the potential of SPR measurements for studying protein-nucleic acid interactions. PMID- 7862524 TI - Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine containing bis-PNA. AB - The synthesis and DNA binding properties of bis-PNA (peptide nucleic acid) are reported. Two PNA segments each of seven nucleobases in length were connected in a continuous synthesis via a flexible linker composed of three 8-amino-3,6 dioxaoctanoic acid units. The sequence of the first strand was TCTCTTT (C- to N terminal), while the second strand was TTTCTCT or TTTJTJT, where J is pseudoisocytosine. These bis-PNAs form triple-stranded complexes of somewhat higher thermal stability than monomeric PNA with complementary oligonucleotides and the thermal melting transition shows very little hysteresis. When the J base is placed in the strand parallel to the DNA complement ('Hoogsteen strand'), the DNA binding was pH independent. The bis-PNAs were also superior to monomeric PNAs for targeting double-stranded DNA by strand invasion. PMID- 7862525 TI - Base sequence determinants of amonafide stimulation of topoisomerase II DNA cleavage. AB - A number of antitumor drugs including naphthalimides, a new class of intercalating agents, interfere with the DNA breakage-reunion activity of mammalian DNA topoisomerase II resulting in DNA cleavage stimulation. In this work, the sequence specificity of a lead compound of this series, amonafide, in stimulating DNA cleavage by murine topoisomerase II has been studied. Amonafide stimulated cleavage intensity patterns were markedly different from those of other antitumor drugs by using pBR322 and SV40 DNAs. This drug had an unusually high site selectivity since about 60% of DNA cleavage was observed at only one site in pBR322 DNA, and at two sites in SV40 DNA. A total of ninety-four drug stimulated sites were collected, and a statistical analysis of their sequences showed that amonafide highly prefers a cytosine, and excludes guanines and thymines instead, at position -1. A lower preference for an adenine at position +1 was also noted. In agreement with the statistical analysis, the DNA sequences of the three sites stimulated by amonafide at exceptionally high levels showed that the drug requirements of a cytosine (-1) and adenine (+1) were present in both the two strands. In addition, a particular feature of these prominent cleavage sites was the presence of an inverted repeat from position -3 to +7. Comparison of amonafide stimulation of DNA cleavage in oligonucleotides bearing base mutations at positions -2, -3 and/or +6, +7 suggested that DNA sequence, and not a putative cruciform structure, was critical for drug action. Moreover, the results showed that, for strong cleavage stimulation, the primary drug requirements at -1 and +1 positions were not sufficient and that the sequence 5' WRC decreases A-3' (W, A or T; R, A or G) is required from -3 to +1 positions at both strands. The results suggest that the exceptionally high sequence specificity of amonafide is the result of optimal drug interactions with both the two enzyme subunits. PMID- 7862526 TI - Yeast transcriptional activator INO2 interacts as an Ino2p/Ino4p basic helix-loop helix heteromeric complex with the inositol/choline-responsive element necessary for expression of phospholipid biosynthetic genes in Saccharomyces cerevisiae. AB - Coordinate transcriptional control of yeast genes involved in phospholipid biosynthesis is mediated by the inositol/choline-responsive element (ICRE) contained in the respective promoter regions. Regulatory genes INO2 and INO4, both encoding basic helix-loop-helix (bHLH) proteins, are necessary for ICRE dependent gene activation. By the use of size variants and by heterologous expression in E. coli we demonstrate that Ino2p and Ino4p are both necessary and sufficient for the formation of the previously described FAS binding factor 1, Fbf1, interacting with the ICRE. Formation of a heteromeric complex between Ino2p and Ino4p by means of the respective bHLH domains was demonstrated in vivo by the interaction of appropriate two-hybrid constructs and in vitro by Far-Western analyses. Neither Ino2p nor Ino4p binds to the ICRE as a homodimer. When fused to the DNA-binding domain of Gal4p, Ino2p but not Ino4p was able to activate a UASGAL-containing reporter gene even in the absence of the heterologous Fbf1 subunit. By deletion studies, two separate transcriptional activation domains were identified in the N-terminal part of Ino2p. Thus, the bHLH domains of Ino2p and Ino4p constitute the dimerization/DNA-binding module of Fbf1 mediating its interaction with the ICRE, while transcriptional activation is effected exclusively by Ino2p. PMID- 7862527 TI - Regulation of fibronectin expression in rat regenerating liver. AB - Fibronectin (FN) expression displays a complex regulation that results in precisely defined isoform patterns during different developmental stages, ageing and injury. The qualitative and quantitative changes that are observed derive from modulation of the rate of transcription of the single FN pre-mRNA and its specific differential processing in the EIIIA, EIIIB and V regions of rat FN. The liver is the major source of plasma FN which is characterised by the absence of the EIIIA and EIIIB exons. Here we show that in the rat regenerating liver there is a significant reprogramming of the splicing machinery that results in the synthesis by the liver of up to 17% of EIIIA+ FN linked with all the three V forms. On the other hand the EIIIB+ form is totally absent both in normal and regenerating liver. Furthermore there is a variation of the V pattern observed in the regenerating tissue, the V120 form (linked to both EIIIA+ and EIIIA- messengers) increases from 11 to 32%. The quantitative RT-PCR method was used to estimate the FN transcription rate, before and after partial hepatectomy. We have shown a 3-fold increase in FN mRNA in liver that is specifically linked to the regeneration process and not to the surgical stress. PMID- 7862528 TI - Structural relationship between DNA polymerases epsilon and epsilon* and their occurrence in eukaryotic cells. AB - Monoclonal antibodies raised against the N-terminal half of human DNA polymerase epsilon bind both to a large > 200 kDa form of DNA polymerase epsilon from HeLa cells and to a small 140 kDa form (DNA polymerase epsilon*) from calf thymus, while antibody against the C-terminal half binds to DNA polymerase epsilon but does not bind to DNA polymerase epsilon*. These results indicate that the two enzymes have common structural motifs in their N-terminal halves, and that DNA polymerase epsilon* is very likely derived from DNA polymerase epsilon by removal of its C-terminal half. DNA polymerase epsilon as well as DNA polymerase epsilon* was detected in extracts from cells of numerous eukaryotic species from yeast to human. The results indicate that DNA polymerase epsilon and its tendency to occur in a smaller form, DNA polymerase epsilon*, are evolutionarily highly conserved and that DNA polymerase epsilon may occur universally in proliferating eukaryotic cells. PMID- 7862529 TI - Cooperation of 5' and 3' processing sites as well as intron and exon sequences in calcitonin exon recognition. AB - We have previously shown that the calcitonin (CT)-encoding exon 4 of the human calcitonin/calcitonin gene-related peptide I (CGRP-I) gene (CALC-I gene) is surrounded by suboptimal processing sites. At the 5' end of exon 4 a weak 3' splice site is present because of an unusual branch acceptor nucleotide (U) and a weak poly(A) site is present at the 3' end of exon 4. For CT-specific RNA processing two different exon enhancer elements, A and B, located within exon 4 are required. In this study we have investigated the cooperation of these elements in CT exon recognition and inclusion by transient transfection into 293 cells of CALC-I minigene constructs. Improvement of the strength of the 3' splice site in front of exon 4 by the branchpoint mutation U-->A reduces the requirement for the presence of exon enhancer elements within exon 4 for CT-specific RNA processing, irrespective of the length of exon 4. Replacement of the exon 4 poly(A) site with a 5' splice site does not result in CT exon recognition, unless also one or more exon enhancer elements and/or the branchpoint mutation U-->A in front of exon 4 are present. This indicates that terminal and internal exons are recognised in a similar fashion. The number of additional enhancing elements that are required for CT exon recognition depends on the strength of the 5' splice site. Deletion of a large part of intron 4 also leads to partial exon 4 skipping. All these different elements contribute to CT exon recognition and inclusion. The CT exon is recognised as a whole entity and the sum of the strengths of the different elements determines recognition as an exon. Curiously, in one of our constructs a 5' splice site at the end of exon 4 is either ignored by the splicing machinery of the cell or recognised as a splice donor or as a splice acceptor site. PMID- 7862530 TI - One short well conserved region of Alu-sequences is involved in human gene rearrangements and has homology with prokaryotic chi. AB - Alu elements have repeatedly been found involved in gene rearrangements in humans. Although these elements have been suggested to stimulate gene rearrangements, sparse information is available for the possible mechanism(s) of these events. Here we present a compilation of Alu elements that have been involved in recombinational events leading to gene rearrangements, indicating the presence of a common 26 bp core sequence at or close to the sites of recombination. Besides the obvious possibility of retrotransposition, gene rearrangements may be induced by sequences that stimulate genetic recombination. We suggest that the core sequence stimulates recombination and may thereby cause the frequent involvement of these elements in gene rearrangements. Curiously, the core sequence contains the pentanucleotide motif CCAGC, which is also part of chi, an 8 bp sequence known to stimulate recBC mediated recombination in Escherichia coli. PMID- 7862531 TI - Mimosine, a novel inhibitor of DNA replication, binds to a 50 kDa protein in Chinese hamster cells. AB - We recently demonstrated that the plant amino acid, mimosine, is an extremely efficacious inhibitor of DNA replication in mammalian cells [P. A. Dijkwel and J. L. Hamlin (1992) Mol. Cell. Biol. 12, 3715-3722; P. J. Mosca et al. (1992) Mol. Cell. Biol. 12, 4375-4383]. Several of its properties further suggested that mimosine might target initiation at origins of replication, which would make it a unique and very useful inhibitor for studying the regulation of DNA synthesis. However, mimosine is known to chelate iron, a cofactor for ribonucleotide reductase. Thus, the possibility arose that mimosine functions in vivo simply by lowering intracellular deoxyribonucleotide pools. In the present study, we show that, in fact, it is possible to override mimosine inhibition in vivo by adding excess iron; however, copper, which is not a substitute for iron in ribonucleotide reductase, is equally effective. Evidence is presented that mimosine functions instead by binding to an intracellular protein. We show that radiolabeled mimosine can be specifically cross-linked to a 50 kDa polypeptide (termed p50) in vitro. Binding to p50 is virtually undetectable in CHO cells selected for resistance to 1 mM mimosine, arguing that p50 is the biologically relevant target. p50 is not associated with the cellular membrane fraction and, hence, is probably not a channel protein. Furthermore, the binding activity does not vary markedly as a function of cell cycle position, arguing that p50 is not a cyclin. Finally, both iron and copper are able to reverse the mimosine-p50 interaction in vitro, probably explaining why both metal ions are able to overcome mimosine's inhibitory effect on DNA synthesis in vivo. PMID- 7862532 TI - Identification of a cDNA for SSRP1, an HMG-box protein, by interaction with the c Myc oncoprotein in a novel bacterial expression screen. AB - We describe a system for screening cDNA expression libraries in Escherichia coli based on protein-protein interactions. The system utilizes fusion proteins containing the DNA binding domain of the lambda phage cl repressor and a heterologous dimerization domain, which is the target of the screen. Such chimeric proteins were functional as transcriptional repressors in E.coli; function was dependent on the presence of the heterologous dimerization domain, and function of the chimeras was disrupted by expression of excess dimerization domain. A screen was designed to identify factors that could interact with the heterologous dimerization domain and thereby inactivate the chimeric repressor. We used this screen to identify factors that could interact with the basic helix loop-helix/leucine zipper domains of c-Myc, and isolated the cDNA for a previously characterized HMG domain protein that interacts specifically with c Myc in this system. This screening method could be used with proteins that have the ability to homo- or heterodimerize. PMID- 7862533 TI - High affinity binding sites for the Wilms' tumour suppressor protein WT1. AB - The Wilms' tumour suppressor protein (WT1) is a putative transcriptional regulatory protein with four zinc fingers, the last three of which have extensive sequence homology to the early growth response-1 (EGR-1) protein. Although a peptide encoding the zinc finger domain of WT1[-KTS] can bind to a consensus 9 bp EGR-1 binding site, current knowledge about the mechanisms of zinc finger-DNA interactions would predict a more extended recognition site for WT1. Using a WT1[ KTS] zinc finger peptide (WT1-ZFP) and the template oligonucleotide GCG-TGG-GCG NNNNN in a binding site selection assay, we have determined that the highest affinity binding sites for WT1[-KTS] consist of a 12 bp sequence GCG-TGG-GCG (T/G)(G/A/T)(T/G). The binding of WT1-ZFP to a number of the selected sequences was measured by a quantitative nitrocellulose filter binding assay, and the results demonstrated that these sequences have a 4-fold higher affinity for the protein than the nonselected sequence GCG-TGG-GCG-CCC. The full length WT1 protein regulates transcription of reporter genes linked to these high affinity sequences. A peptide lacking the first zinc finger of WT1[-KTS], but containing the three zinc fingers homologous to EGR-1 failed to select any specific sequences downstream of the GCG-TGG-GCG consensus sequence in the binding site selection assay. DNA sequences in the fetal promoter of the insulin-like growth factor II gene that confer WT1 responsiveness in a transient transfection assay bind to the WT1-ZFP with affinities that vary according to the number of consensus bases each sequence possesses in the finger 1 subsite. PMID- 7862534 TI - Stabilization of double-stranded oligonucleotides using backbone-linked disulfide bridges. AB - A convenient, practical route to the synthesis of disulfide-bridged oligonucleotides has been developed. Aliphatic linkers with terminal thiol groups have been attached to the phosphodiester backbones of partially or fully complementary oligonucleotide sequences and oxidized to yield covalently closed oligonucleotides with disulfide bridges. This procedure has been used to prepare a duplex with disulfide bridges at both ends and stem-loop sequences with single disulfide bridges. Oxidation of a self-complementary duplex possessing terminal thiol groups produced both hairpin and duplex structures with disulfide bridges, the relative proportions of each being dependent upon the reaction conditions. These bridged hairpin and duplex structures were shown to be interconvertible by reduction and re-oxidation. The melting profiles of disulfide-bridged oligonucleotides were compared with the same sequences without bridges and with sequences possessing triethylene glycol bridges, and in all cases the introduction of disulfide bridges resulted in a considerable increase in thermal stability. EcoRI endonuclease was capable of cleaving a disulfide-bridged duplex possessing a recognition site for this enzyme, thus supporting a lack of distortion of the recognition site. The disulfide bridges could be cleaved using a large excess of DTT to regenerate the corresponding sulfhydryl compounds. A study of the serum stabilities of disulfide-bridged oligonucleotides showed that the bridged duplexes were much more stable than their unmodified counterparts, whereas the rate of degradation of the stem-loop structures was more dependent upon the size of the loop than the presence or absence of the disulfide bridge. In summary, we have described a novel methodology, employing commercially available reagents, for the stabilization of oligonucleotide duplexes or stem loop structures by disulfide bridge formation. PMID- 7862536 TI - Establishment of an autocatalytic conditional mammalian system for expression of stringently regulated genes. PMID- 7862535 TI - Identification of a 27 bp 5'-flanking region element responsible for the low level constitutive expression of the human cytosolic phospholipase A2 gene. AB - The cytosolic phospholipase A2 (cPLA2) gene codes for an enzyme that liberates arachidonic acid from membrane phospholipids, and thus plays a pivotal role in the production of the prostaglandin and leukotriene mediators of inflammation, as well as in a variety of cell signalling pathways. After preliminary studies demonstrated the cPLA2 gene is expressed in a variety of human tissues and was localized to the q arm of chromosome 1 between markers F13B and D1S74, we cloned and characterized the 5'-flanking region of this gene in order to identify the elements controlling its low level constitutive expression. The 5'-flanking region has features typical of a housekeeping gene with no TATA box or CAAT box, although atypical in that it is not GC rich, has no SP1 sites, and has a long run of CA repeats. Analysis of fragments of the 5'-flanking region demonstrated that 541 bp 5' to exon 1 supported reporter gene activity at a level 30% of the SV40 promoter. Interestingly, similar activity was observed by deleting most of the 5' flanking region down to a 27 bp region containing a sequence with homology to the initiator sequence in the terminal deoxynucleotidyl transferase gene and a polypyrimidine tract similar to the initiator element of the mouse ribosomal protein gene. Within this 27 bp region, a 10 bp fragment (-17 to -8 bp) within the polypyrimidine tract is critical for the baseline expression of the human cPLA2 gene. While the 5'-flanking region contains a putative composite AP-1 and glucocorticoid response element, this region does not respond to tumor necrosis factor-alpha (TNF) and/or glucocorticoids in a cell line (HEp-2) that exhibits upregulation of cPLA2 mRNA transcript levels by TNF. The observations that the expression of the cPLA2 gene is tightly controlled at a relatively low level is consistent with the evolving concept that modulation of expression of this critical enzyme is primarily at the post-translational level. PMID- 7862537 TI - Express protocol for generating G+A sequencing ladders. PMID- 7862538 TI - 3'-5' proofreading-induced detection of point mutations by PCR using Tli DNA polymerase. PMID- 7862539 TI - The paradox of comfort. AB - Patients who had experienced major illness, surgery, or trauma were asked to "tell their stories." Using a phenomenological method, eight themes emerged that reflected the experience of the lived body (corporeality) associated with discomfort. These were the dis-eased body, the disobedient body, the deceiving body, the vulnerable body, the violated body, the resigned body, the enduring body, and the betraying body. To patients, comfort is not an ultimate state of peace and serenity, but rather the relief, even temporary relief, from the most demanding discomfort. Illness and injury place patients' bodies into the foreground, dominating their attention and disrupting their accustomed orientation to the world. Thus, an understanding of patient comfort that is linked with discomfort and empowers or strengthens patients in relation to their bodies provides important insight. The authors argue that attaining comfort is a paradox best understood by reflecting not on the concept of comfort per se, but on its converse. This supports, rather than negates, the construct of comfort as the goal of nursing care. PMID- 7862540 TI - Health-promoting lifestyles of blue-collar, skilled trade, and white-collar workers. AB - The health-promoting lifestyles of blue-collar, skilled trade, and white-collar workers were examined. Specific purposes included determining differences in health-promoting behaviors, especially according to worker category, as well as ethnic identification, age, gender, education, and marital status. A convenience sample of 638 workers in a midwestern automotive components plant completed the Health-Promoting Lifestyle Profile (HPLP) and demographics questionnaire. In a multivariate analysis of variance (MANOVA) including all demographic variables, significant differences were found in the mean scores on subscales of the HPLP by job category (2 subscales), age (3), gender (2), and education (4). Prior to including education in the MANOVA, significant differences were found by job category on 5 subscales of the HPLP. The effects of education eliminated the majority of the effects of job category. PMID- 7862541 TI - Structural and interpersonal impact of heterosexual assumptions on lesbian health care clients. AB - In this feminist narrative study using in-depth interviews and focus groups, a racially and economically diverse sample of 45 lesbians described their access to and experience with health care. The multistaged narrative analysis revealed structural and interpersonal conditions uniquely faced by lesbians in obtaining health care services. At the macrolevel, heterosexist structuring of health care delivery was obstructive to lesbians' health care seeking, health knowledge, and health behaviors. At the micro, or individual level, health care providers' heterosexual assumptions competed against potentially supportive interactions with lesbian clients. PMID- 7862542 TI - Rx for a healthy NINR. PMID- 7862543 TI - Paternal-infant attachment of experienced and inexperienced fathers during infancy. AB - Seventy-nine experienced fathers (with one or more previous children) and 93 inexperienced (first-time) fathers were studied for differences in paternal infant attachment at postpartal hospitalization and at 1, 4, and 8 months following birth. No significant differences were observed between the groups for reported attachment to their infants; scores varied little. Over the 8-month period, from 27% to 47% and from 9% to 22% of the variance in attachment was explained for experienced fathers and inexperienced fathers, respectively. Fetal attachment was a major predictor for attachment for experienced fathers at the first three test periods, explaining 19% of the variance at early postpartal hospitalization, 16% at 1 month, and 9% at 4 months. It was a major predictor for inexperienced fathers the first month only, explaining 13% of the variance at early postpartal hospitalization and 15% at 1 month. Depression was the second most important predictor. For experienced fathers, it explained 8% of attachment at early postpartum and 22% at 8 months; for inexperienced fathers, it explained 7% at 1 month and 9% at 4 months. Environmental factors such as social support and stress had no effects on fathers' attachment to their infants. PMID- 7862544 TI - Motor performance correlates of functional dependence in long-term care residents. AB - The purpose of this study was to examine the validity and reliability of the Motor Performance Inventory (MPI), a series of upper and lower extremity movements for predicting functional dependence and independence. A random sample of 197 persons, aged 65 and above, who resided in one of eight extended care facilities, were stratified as independent, assist (intermediate), or dependent using modified 1990 Health Care Financing Administration (HCFA) operational criteria. A stepwise procedure yielded a five-task combination that accounted for 90% of the variance in functional level. The final model accurately predicted group membership 72% of the time. PMID- 7862545 TI - Predicting Head Start parent involvement in an alcohol and other drug prevention program. AB - This study examined Health Belief Model predictors of parent involvement with preschool children in an alcohol and other drug (AOD) prevention program. Over 300 Head Start parents were invited to participate in BABES (Beginning Alcohol and Addictions Basic Education Studies) with their children once a week for 7 weeks. Two hundred parents completed self-report instruments prior to participation in BABES. Previous classroom involvement, barriers, county, and race predicted high attendance (3 to 7 lessons). AOD use severity, benefits, and role modeling predicted low attendance (1 to 2 lessons). Further research involving manipulation of external cues, parent involvement in nonclassroom settings, and race-homogeneous samples is recommended. PMID- 7862546 TI - A comparison of the effects of jaw relaxation and music on postoperative pain. AB - This experimental study compared the effects of jaw relaxation and music, individually and combined, on sensory and affective pain following surgery. Abdominal surgical patients (N = 84) were randomly assigned to four groups: relaxation, music, a combination of relaxation and music, and control. Interventions were taught preoperatively and used by subjects during the first ambulation after surgery. Indicators of the sensory component of pain were sensation and 24-hour narcotic intake. Indicators of the affective component of pain were distress and anxiety of pain. With preambulatory sensation, distress, narcotic intake, and preoperative anxiety as covariates, the four groups were compared using orthogonal a priori contrasts and analysis of covariance. The interventions were neither effective nor significantly different from one another during ambulation. However, after keeping the taped interventions for 2 postoperative days, 89% of experimental subjects reported them helpful for sensation and distress of pain. PMID- 7862547 TI - Re: 'Factors associated with risk of stress urinary incontinence in women'. PMID- 7862548 TI - Re: 'Regression analyses: what to report'. PMID- 7862549 TI - Developing a measure of sense of belonging. AB - The purpose of this study was to develop and test psychometrically a self-report instrument designed to measure sense of belonging in adults. The Sense of Belonging Instrument (SOBI) is a 27-item, self-report instrument consisting of two separately scored scales, SOBI-P (psychological state) and SOBI-A (antecedents). Content validity was assessed by a panel of experts. Construct validity, internal consistency, and retest reliability were examined through a series of studies with three subject groups: community college students, patients in treatment for major depression, and Roman Catholic nuns. Results suggest that SOBI-P is a valid and reliable measure of sense of belonging. SOBI-A appears to reflect an individual's motivation for sense of belonging but requires additional study regarding its construct validity and internal consistency. PMID- 7862550 TI - Professional development. Lifting and handling: revision notes (continuing education credit). PMID- 7862551 TI - HIV risk and men with learning disabilities. PMID- 7862553 TI - Helping with inquiries. Interview by David Payne. PMID- 7862552 TI - On the brink. PMID- 7862554 TI - Making the grade. PMID- 7862555 TI - Violence. Hitting back at the bullies. PMID- 7862556 TI - Violence. Dealing with a hostage situation. PMID- 7862557 TI - Strategies for managing auditory hallucinations. AB - Auditory hallucinations are frequently experienced as distressing and intrusive. Although neuroleptic medication helps a considerable number of people, many obtain little benefit and continue experiencing voices long after discharge from hospital. Recent years have witnessed the development of a number of psychological techniques for helping individuals manage their voices. This paper reviews some of the recent literature and describes how a number of these strategies can be used to help individuals gain control over their hallucinations and so reduce the level of distress experienced. PMID- 7862558 TI - Testing the feasibility of timed district nurses' visits. AB - A pilot scheme implemented in Oldham by district nurses determined the feasibility of providing patients in the community with timed visits. In keeping with the government's Patient's Charter initiative the scheme aims to improve the standard of care offered to patients and their informal carers. PMID- 7862559 TI - Pathology testing of blood glucose levels. AB - Reduced and raised blood glucose concentration (hypoglycaemia and hyperglycaemia respectively) are symptoms of a number of conditions besides diabetes mellitus. The third paper in our series describes these conditions and methods used to assess blood glucose levels. PMID- 7862560 TI - International perspectives. Tribal quest. PMID- 7862561 TI - Let's grow up. PMID- 7862562 TI - Infection control. The history of plague. PMID- 7862563 TI - Infection control Hazards in HSDU (hospital sterile services). PMID- 7862564 TI - Drama in the theatre. PMID- 7862565 TI - War of independence. Interview by Anne Taylor. PMID- 7862566 TI - Bug in the system. Interview by David Payne. PMID- 7862567 TI - Letter from America. PMID- 7862568 TI - Hand in glove. PMID- 7862570 TI - Advocacy. Whose best interest? PMID- 7862569 TI - Support for advocacy. PMID- 7862571 TI - Advocacy. Meeting the challenges. PMID- 7862572 TI - Quality indicators for patient information in short-stay units. AB - In 1993, a prospective audit of short-stay, general surgery patients assessed consumer knowledge and satisfaction with available information, identifying how current practice might be improved. The audit revealed that more formalised discharge procedures might improve patients' understanding of what to expect as convalescence progressed, increasing their knowledge for appropriate self-care. Community costs were also assessed. PMID- 7862573 TI - The effects of botulinum toxin on ocular tissue. AB - This report examines the beneficial use of botulinum toxin in the treatment of ophthalmic disorders. It aims to describe the effects and uses of the toxin along with the ophthalmic conditions it is used to treat. The use of botulinum toxin as an effective treatment of ophthalmic disorders is a recent development, with the first treatment occurring in 1983. PMID- 7862574 TI - The problem of hospital-induced malnutrition. AB - This paper discusses the problem of hospital-induced malnutrition. Patients particularly at risk are identified and the causes of PEM are outlined. PMID- 7862575 TI - Day care for women with high-risk pregnancies. AB - This report describes a study carried out at Glasgow Royal Maternity Hospital which examined women's perceptions of the care they received for hypertension during pregnancy at a day care unit. Thirty women were asked about the advantages and disadvantages of day care. Additionally, they were asked to assess how often they would be willing to attend day care each week, to avoid a seven-day admission. The overwhelming view of day care was positive. None of the women would rather be an in-patient than attend day care, and the majority would attend day care five times a week to avoid admission. Information of this type is of use to staff in such units, since it is very important that women with complications during pregnancy are confident about the care they are receiving. PMID- 7862576 TI - Innovation in commissioning. PMID- 7862577 TI - Asthma peak flow meters. PMID- 7862578 TI - Body politic. The last stand? PMID- 7862579 TI - Ageing matters. In their own best interests. PMID- 7862580 TI - Ageing matters. Guiding principles. PMID- 7862581 TI - [Neuropeptides "Y" in regulation of the cardiovascular system]. PMID- 7862582 TI - [Blood pressure in young men with a family history of primary hypertension- traditional and 24-hour blood pressure measurements]. AB - Blood pressure was measured in two groups of young males-group S-55 men with positive family history of essential hypertension (EH) and group K-11 men with negative family history of EH (mean age 24.5 +/- 3.3 and 23.5 +/- 4.7 years). Two methods of blood pressure measurement--traditional blood pressure measurement (method A) and automatic ambulatory indirect blood pressure monitoring (method B) were used. Blood pressure was higher in group S than in group K-method A 140 +/- 14/86 +/- 10 vs 122 +/- 10/73 +/- 8 mm Hg; method B: 132 +/- 11/78 +/- 10 vs 123 +/- 8/72 +/- 7 mm Hg. Contrary to group K, in group S discrepancies in the frequency of diagnosis of systolic or diastolic hypertension were found between the two methods of blood pressure measurement. These results indicate that in young males the traditional method of blood pressure measurement may provide a false positive diagnosis of hypertension, but both methods of blood pressure measurement used in this work were effective in the diagnosis of normotension. As a population the young males with positive family history of EH have higher blood pressure then young males with negative family history of EH. PMID- 7862583 TI - [Isometric exercise and cold pressor test in young men with a family history of essential hypertension]. AB - An exaggerated pressor reaction to the isometric exercise and cold pressor test (CPT) is found to be a predictor or future hypertension. In the two groups of young males: 51 men with positive family history of essential hypertension (EH) (mean age: 24.3 +/- 3.3 years, group S) and 11 men with negative history of EH (mean age: 23.5 +/- 3.7 years, group K) the blood pressure responsiveness to the handgrip test (HG) and CPT were evaluated. Ambulatory systolic (SBP) and diastolic (DBP) blood pressure were higher in S then K (respectively: 136 +/- 11/81 +/- 10 mm Hg vs 126 +/- 4/76 +/- 6 mm Hg, p < 0.05). The elevation of blood pressure after HG (30% of maximal voluntary contraction for 3 min.) was higher in K than S (respectively: delta SBP = 37 +/- 20 vs 21 +/- 17 mm Hg i delta DBP = 27 +/- 20 vs 7 +/- 12 mm Hg, p < 0.05). Similarly, after CPT (by immersing the left hand and forearm in ice-cold water for 2 min.) the elevation of blood pressure was higher in K than S (respectively: delta SBP = 22 +/- 11 vs 12 +/- 12 mm Hg i delta DBP = 17 +/- 12 vs 9 +/- 9 mm Hg, p < 0.05). These results do not confirm an exaggerated blood pressure responsiveness to the HG test or CPT in young males with positive family history of EH, irrespectively to the diagnosis of normotension or borderline hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862584 TI - [Comparison of the effect of short-term treatment with nifedipine and verapamil on blood pressure, plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) in patients with primary arterial hypertension I degree according to WHO]. AB - The aim of the study was the comparison of the effect of seven day treatment with nifedipine (2 x 10 mg daily) and subsequently with verapamil (3 x 40 mg daily) on blood pressure, heart rate, plasma ANP, cGMP, renin activity (PRA), aldosterone (ALDO) concentrations in patients with primary hypertension. The material consisted of 12 untreated patients with primary arterial hypertension Io WHO. These results suggest that short-term treatment with nifedipine and subsequently with verapamil in patients with primary hypertension Io WHO not influence on plasma ANP, cGMP, PRA and ALDO in spite of blood pressure reduction and the changes in heart rate. It seems that ANP did not participate in hypotensive action of nifedipine and verapamil. No augmentation of urinary sodium excretion was found after short-term treatment with nifedipine or verapamil. PMID- 7862585 TI - [Use of nifedipine in elderly patients with essential hypertension: patient compliance, safety and efficacy of therapy]. AB - The aim of the study was to evaluate chronic treatment with Cordafen (nifedipine) in the out-patients over 60 years of age with established arterial hypertension. Out of 100 out-patients aged 60-83 years 69 subjects completed one-year study. The main reasons of drop-outs were: lack of patient compliance (12%), severe side effects (11%), ineffective monotherapy (5%) and other (3%). Less severe adverse effects were found in further 20 subjects. After one-year therapy hematological and biochemical parameters of the homeostasis did not deteriorate except an increase in alkaline phosphatase. Regular drug intake in a dose of 20-80 mg/daily (mean = 46.0) produced a significant decrease in the blood pressure level and an improvement of cardiac function indices (CO nad EF). In contrast Cordafen did not reduce the differences between extreme blood pressure values recorded automatically, and it did not produce a significant regression of left ventricular mass and cardiac arrhythmias. Nifedipine in mild or moderate hypertension in the elderly patient any be an adequate form of monotherapy in about 70% of them. Higher motivation for treatment in this age group and better drug tolerance may further improve this efficacy. PMID- 7862586 TI - [Hyponatremia and hypernatremia in the elderly]. AB - The study aimed at evaluating an incidence of hypo- and hypernatremia in the elderly and the results of therapy. Hyponatremia. The studies involved 18 patients aged 69.8 +/- 5.9 years with hyponatremia of 126.8 +/- 2.7 mmol/L. The main causes of hyponatremia were: diuretics, diarrhoea, and vomiting. Sodium deficit was calculated prior to the treatment in all patients. An analysis of hyponatremia incidence indicates that hyponatremia was diagnosed in 1.39% of patients over 60 years, hospitalized within 1989-1990. Sodium deficit in this group was 495.5 +/- 167.7 mmol. Sodium chloride solution was given intravenously to 12 patients, according to the "free correction" principle (a mean increase in serum sodium level was 0.17 +/- 0.07 mmol/L per hour). Mortality in such treated patients was 33%. Sodium chloride was not given to 6 out of examined patients. In 12 patients (66.6%) hyponatremia developed prior to hospitalization, in 6 patients (33.3%) during hospitalization. Mortality rate was 16.6% and 50%, respectively. This confirms higher mortality rate of the rapidly developing hyponatremia in the hospitalized elderly patients. In some cases hyponatremia may constitute iatrogenic complication, especially in the elderly given diuretics in an uncontrollable way. Own experience suggests that elderly patients with a risk of hyponatremia require close monitoring and early compensation of the electrolyte disorders. Hypernatremia. The studies involved 20 patients aged 71.4 +/- 7.7 years with hypernatremia of 155.6 +/- 8.4 mmol/L. A total water deficit (DH20) was calculated in this group. An analysis of hypernatremia incidence showed that this state was diagnosed in 1.55% of patients treated at the Department of Arterial Blood Hypertension within 1989-1990. Total water deficit was 3.9 +/- 1.9 L. A 5% glucose was given intravenously to 15 patients whereas oral fluid therapy was carried out in 5 patients. A mean corrected DH2O in the first day was 46.0 +/- 21.0%. Mortality rate in this group was 65%. It is worth mentioning that 37% of patients with chronic hypernatremia which developed prior to hospitalization died while in case of the acute hypernatremia developed in the hospital mortality rate was 83%. A significant effect on the results of therapy plays an early correction of hypernatremia. Mortality rate in case of DH2o supplementation below 30% during the first 24 hours is about 66%., if DH2o supplementation is 31-60%, a mortality rate is 63%, and in DH2o supplementation over 60% mortality rate is 100%. The obtained results suggest that hypernatremia in the elderly is related to the high mortality rate (65%). An early decrease of water deficit increases mortality rate in patients with hypernatremia. PMID- 7862587 TI - [Excretion of beta-2-microglobulin in hypertension]. AB - The study aimed at evaluating an excretion of beta 2-microglobulin with the urine of hypertensive patients. Thirty patients with mild-to-moderate hypertension (diastolic blood pressure 14.26 +/- 0.86 kPa) and 13 patients with severe hypertension (diastolic blood pressure 17.8 +/- 1.7 kPa) were included into the studies. Significantly increased beta 2-microglobulin excretion with the urine was noted in both groups with the highest values in patients with severe blood hypertension. Moreover, significant correlation between tubular reabsorption of beta 2-microglobulin and diastolic blood pressure was noted in both groups. Increased excretion of beta 2-microglobulin in the arterial hypertension may be due to an increased glomerular filtration of this protein and/or decreased reabsorption in proximal tubule. PMID- 7862588 TI - [Hemodynamic profile of primary arterial hypertension in the elderly]. AB - Cases of the primary arterial hypertension in the elderly (over 60 years of age) have been analysed. It has been found that approximately 70% of patients have had systolic-diastolic hypertension and the remaining 30%--diastolic hypertension. Cardiac output, cardiac index, peripheral resistance, left ventricle activity index, and SV with pulse rate multiplied by diastolic blood pressure had been determined with impedance rheography. Significant individual differences in the value of the analysed indices have been noted. Systolic-diastolic arterial hypertension was characterized by a decrease in SV and increase in peripheral resistance whereas dominating systolic hypertension was was manifested by a significant increase in peripheral vascular resistance. Other indices have not differentiated both forms of the arterial hypertension. PMID- 7862589 TI - [Changes of components in the kinin system and plasma renin activity during different stages of hypertension in patients treated with captopril]. AB - The authors aim was to evaluate if the changes in the components of the plasma kinin system on PRA, determined during 3-weeks period of treatment with captopril in daily doses of 150 mg, depend on the stage of arterial hypertension. Investigations were carried out in 40 patients with primary hypertension; 6 patients were in I, 20 in II and 14 in III WHO stage. The control group consisted of 18 healthy persons. All the parameters were examined 3 times: before therapy, after 24 h and after 3 weeks of therapy. It was proved that captopril as monotherapy, was effective in every stage of hypertension, however the normalisation of blood pressure was observed only in I and II WHO stage. The normalisation of the prekallikrein levels appeared after 3 weeks of treatment in all periods of hypertension, while the normalisation of the kininogen levels occurred only in patients of I and II WHO stage. Since changes of kininogen level in plasma occurred along with changes in blood pressure, therefore the estimation of kininogen seems to be better criterium of effectiveness of captorpil than the determination of prekallikrein. The changes of PRA were similar in all stages of hypertension, but they were significant only in the group of patients of II WHO stage and only after 24 h. Presented studies indicate that renin-angiotensin aldosterone system as well as kinin system, participate in the mechanism of antihypertensive effect of captopril in every stage of hypertension. PMID- 7862590 TI - [Role of opioid receptors and hormones participating in volemic regulation in pathogenesis of arterial hypertension in patients with glomerulonephritis and pyelonephritis]. PMID- 7862591 TI - [Isolated systolic hypertension]. PMID- 7862592 TI - [Diagnosis of early hypertension with continuous ambulatory blood pressure monitoring]. AB - Characteristics of a 24-hour blood pressure monitoring and its usefulness in the diagnosis of early hypertension have been discussed. Measurements of ambulatory blood pressure in normotensive individuals are lower than those achieved with continuous monitoring at daytime whereas the situation in hypertensive subjects is reverse. Office blood pressure measurements produce higher values already in borderline hypertension and may use as differentiating diagnostic parameter. Continuous blood pressure monitoring enables to detect "white coat hypertension" estimated to occur in 7% of the general population and in 21% of patients with mild hypertension. Even a few hours of the continuous blood pressure monitoring identifies subjects with "white coat hypertension" and office hypertension and consequently avoidance of the unnecessary pharmacologic treatment. Ambulatory blood pressure monitoring is also useful in the diagnosis of early hypertension in adolescents provided that the tests will be carried out during school hours. Some investigators believe that the proportion of abnormal measurements (over 140/90 mm Hg), i.e. so-called blood pressure load, is more important at early stages of the disease because there closer correlation between blood pressure and organ damage than mean values of blood pressure. However, it was not established yet what is a percentage of abnormal blood pressure measurements in normotensive and hypertensive subjects. Blood pressure circadian rhythm in various groups but the highest changes are found in borderline hypertension. Blood pressure variability expressed as standard deviations from the mean values calculated from the ambulatory blood pressure monitoring is an individual feature considered also as a predictor of hypertension development with all its sequelae. PMID- 7862593 TI - [Clinical experience with use of variable magnetic fields]. PMID- 7862594 TI - Arthritis patient education standards: a model for the future. PMID- 7862595 TI - Evaluation of a rheumatoid arthritis patient education program: impact on knowledge and self-efficacy. AB - We have evaluated the effects of an education program on the knowledge and self efficacy of 51 rheumatoid arthritis patients, using two previously validated questionnaires. At completion of the program, both knowledge and self-efficacy were significantly improved and this was maintained at follow-up. However, there was no correlation between knowledge and self-efficacy at baseline and follow-up, suggesting that these variables improved independently of each other. We conclude that education programs are a worthwhile means of improving the non-medical causes of morbidity in rheumatoid arthritis patients and that the two instruments utilized are a valuable means of both demonstrating effectiveness and quality assurance. PMID- 7862596 TI - Psychological, demographic and situational factors of family physicians which influence cigarette cessation interventions in office-based practice. AB - Sixty-five office-based family physicians completed a mailed questionnaire which sought to determine the extent to which these physicians offer cigarette cessation interventions to their patients. This information was related to 44 scales from 7 psychological tests completed by each physician during residency training. Ninety percent of these physicians intervene personally, while outside referral to an expert and internal referral to a nurse were each utilized by less than 12% of the sample. Over 45% of these private practitioners used supplemental video or written materials. A number of psychological characteristics but no demographic or situational variables discriminated physicians regarding the implementation of these cigarette cessation interventions. PMID- 7862597 TI - Patient's understanding of health information: a multihospital comparison. AB - Patient education is an integral component of the care most hospital patients receive. The use of printed health material is widespread due to its perceived benefit and convenience. Unfortunately, there is a discrepancy between reading level of many materials selected for patients and the reading ability of the intended reader group. Although research suggests the need for simplified text, ease of reading is only one component of readability; the other is comprehension. This article presents results from a study completed in 1990 and replicated in two hospitals the following year. Using a Cloze technique, researchers tested patient's ability to understand health information prepared at grade levels five and nine. Scores revealed that 77% of subjects were able to comprehend material prepared at the grade five level independently, 8% required some assistance, and 14% were not able to comprehend the material. When comprehension of the material prepared at the grade nine level was tested only 30% of subjects were able to comprehend it, 31% required some help, and 39% were unable to comprehend it. These results suggest the importance of simplifying health material to no higher than a grade five level so it is comprehensive to the majority of hospital patients. PMID- 7862598 TI - Evaluation of the short-term impact of counseling in general practice. AB - This paper describes the findings of a randomised controlled trial of the short term impact of counseling in the general practice setting. Compared with patients who received usual advice from their general practitioner for acute problems such as relationship difficulties, anxiety and depression, those who received counseling from qualified counselors working within the primary health care context showed greater improvement in psychological health as measured by the General Health Questionnaire. Significantly fewer of those counselled were prescribed anti-depressant drugs by the general practitioners in the study, or were referred to psychiatrists or clinical psychologists for care. In addition those patients who attended sessions with the practice counselor were more likely to report that they were satisfied with their treatment and more expressed feelings of well-being. PMID- 7862599 TI - Arthritis patient education studies, 1987-1991: a review of the literature. AB - Arthritis is a chronic disease that is estimated to affect 14.5% of the American population and is the leading cause of functional dependency in the activities of daily living (ADLs) and the instrumental activities of daily living (IADLs) in all persons over the age of 65 years. Clinical studies have shown that medical care, including the use of medications, can offer a 20-50% improvement in reported arthritis symptoms. Data from patient education studies suggest that a further improvement of 15-30% is attainable through patient education interventions. This literature review has been completed to update the reviews of patient education studies by Lorig and Riggs in 1983 and Lorig, Konkol, and Gonzalez in 1987. More specifically, the objectives of this review are: (1) to provide a summary of arthritis patient education studies published or presented since 1987; (2) to summarize the findings concerning the effectiveness of arthritis patient education studies which attempt to change knowledge, behavior, psychosocial status, and health status; (3) to discuss shifting trends in observed outcomes of arthritis patient education studies; and (4) to discuss implications for the future. PMID- 7862600 TI - Self-care materials in the practice of cardiology: an explorative study among American cardiologists. AB - American practitioners were surveyed about the role of self-care materials in the management of cardiology patients. Respondents indicated their patients commonly use self-care materials and seek recommendation of appropriate readings. Over half those responding had reviewed 'some' popular works, but few had been able to keep up with this literature. The great majority of responders found self-care materials sometimes helpful to patients, considered certain works particularly helpful, and made recommendations to patients; many agreed that certain published works might be harmful. AHA publications were most frequently endorsed, followed by Dr Dean Ornish's Program for Reversing Heart Disease and The New American Diet. Patients were cautioned by some physicians to avoid certain other titles. Greater professional effort to evaluate the appropriateness of popularized self care works for cardiology patients is needed. PMID- 7862601 TI - Nonlinear effects of chicken endogenous viruses on body weight may be responsible for maintaining these elements in a stable genetic polymorphism. AB - The effects of presence or absence of individual endogenous virus (ev) genes on production traits was studied in a highly productive commercial layer cross. Age and BW at first egg, egg production, egg weight, and mature BW were recorded for each bird. The birds were examined for presence of ev gene fragments by Southern analysis. A general linear model was used to determine significance of effects of the 21 individual ev fragments on the individual traits and the effects of all ev fragments taken together on each of the traits. Seven significant effects were found for individual ev fragments on individual traits. Four of these involved BW at first egg, and all ev gene fragments taken together had a significant effect on BW at first egg, explaining 17% of total phenotypic variation in this trait. Significant nonlinear correlations were found between total number of ev genes and both BW at first egg and mature BW, with birds having a moderate number of ev genes showing the lowest BW. For age at first egg and egg weight, nonlinear correlations, although not significant, were consistent in sign with those found for BW, implying minimum trait magnitude at moderate number of ev genes. These effects imply that animals with intermediate numbers of ev genes will tend to be favored by commercial selection in layer flocks, whereas birds with either too many or too few ev genes will tend to be culled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862602 TI - Embryonic adenosine triphosphate:phosphodiesters ratios obtained with in vivo nuclear magnetic resonance spectroscopy (phosphorus-31): a new technique for selecting leaner broiler chickens. AB - Phosphorus-containing compounds of 18-d-old embryos from two broiler chicken lines, differing in body fat content, were measured using in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Subsequently, the same birds were slaughtered at 8 wk of age and the whole body was analyzed for body fat content. The birds of the fat line had lower (P = .002) embryonic adenosine triphosphate (ATP):phosphodiester (PDE) ratios, higher (P = .002) body fat content when adjusted to common BW, and higher (P = .047) dry matter content than the lean line. No differences (P > .05) were detected for BW between the two lines. Females of the two lines had lower (P = .002) ATP:PDE ratios, lower (P = .001) BW, higher (P = .003) adjusted fat contents, and higher (P = .003) dry matter content than the males. No interaction (P > .05) between sexes and lines was detected for any variables. Regression equations indicating a linear negative relationship (Ybody fat content = 369.05 - 407.27 XATP:PDE + .1295 XBW, R2 = .62 to .78; or Ybody fat % = 30.57 - 19.4 XATP:PDE, R2 = .49 to .71) between embryonic ATP:PDE ratios and body fat content were developed. PMID- 7862603 TI - Responses to long-term divergent selection for eight-week body weight in chickens. AB - Thirty-six generations of divergent selection for body weight at 8 wk of age resulted in approximately an eightfold difference between the high (HWS) and low (LWS) lines for this trait. In both White Plymouth Rock lines, selection intensities declined over generations, with responses about five times greater during the first 18 than the last 18 generations of selection in Line HWS and about two times greater in Line LWS. Also, responses to selection were more irregular in the later than in earlier generations. Sexual dimorphism of body weight (male:female) was greater for Line LWS than HWS. A randombred control line (AC) maintained concurrently with the selected lines did not exhibit environmental trends across generations. Relaxed lines, established at different generations of selection, were used to evaluate effectiveness of selection and monitor environmental changes over short periods. PMID- 7862604 TI - Lack of interactions between dietary lysine or strain cross and photoschedule for male broiler performance and carcass yield. AB - The purpose of this study was to test interactions of dietary lysine or strain crosses provided increased lysine with photoschedule on broiler performance and carcass quality. In Experiment 1, treatments were factorially arranged as two lysine levels [control grower and finisher (NRC, 1984) or control grower and finisher plus .15% L-lysine HCl] and two photoschedules [23 h light (L):1 h dark (D) or 14L:10D]. All birds received a control starter feed and dietary treatments were initiated at 22 d of age. In Experiment 2, treatments were factorially arranged as two strain crosses [Peterson x Arbor Acres (PAA) or Ross x Ross (RR)] and two photoschedules (23L or 16L). All birds received standard starter and standard grower and finisher plus .15% L-lysine HCl. There were no lysine by photoschedule or strain cross by photoschedule interactions in this study. The high-lysine diet increased BW, improved feed efficiency, increased lean carcass weight and yield of breast meat, and decreased abdominal fat and yield of thighs. The PAA strain cross had better feed conversion, fewer Grade A carcasses, more back bruises and breast blisters, greater yield of wings and drumsticks, and less yield of breast meat than RR. The 23L had greater BW, better feed efficiency, fewer breast blisters, greater carcass weight (Experiment 1), more abdominal fat (Experiment 2), lower yield of wings (Experiment 1), drumsticks, and thighs, and greater yield of breast meat than the treatments with shorter photoschedules. Increased dietary lysine did not compensate for decreased breast meat yield associated with 14L (Experiment 1). PMID- 7862605 TI - Effects of dietary supplementation with lactosucrose (4G-beta-D galactosylsucrose) on cecal flora, cecal metabolites, and performance in broiler chickens. AB - The effects of dietary lactosucrose on cecal flora, cecal metabolites, and performance were studied in eight 20-d-old and eight 62-d-old broiler chickens fed a basal diet (control) or a diet with .15% lactosucrose added. On Day 20 of age, the frequency of occurrence of lecithinase-negative clostridia were decreased (P < .05) by lactosucrose consumption. On Day 62 of age, the numbers of bifidobacteria were increased (P < .05) by lactosucrose consumption, but the counts of lecithinase-positive clostridia, including Clostridium perfringens, bacteriodaceae, and staphylococci, total anaerobic bacteria, and the frequency of occurrence of pseudomonads were decreased (P < .05). No detectable change was observed in counts of other organisms throughout the experimental period. Cecal concentration of ammonia (P < .01), phenol (P < .05), and cresol (P < .05) were decreased on Day 62 of lactosucrose consumption. Acetic acid and butyric acid were increased (P < .01 and P < .05, respectively) on Day 62 of lactosucrose consumption. Environmental ammonia and odor of chicken ceca were greatly reduced by lactosucrose consumption. PMID- 7862606 TI - Adenosine triphosphate bioluminescence as a method to determine microbial levels in scald and chill tanks at a poultry abattoir. AB - According to Hazard Analysis of Critical Control Points (HACCP) programs developed for the poultry industry, poultry processing waters should be actively monitored to minimize cross-contamination between chicken carcasses. In order to monitor HACCP programs, a test is required that provides results on a real time basis. A modified adenosine triphosphate (ATP) bioluminescence test has been developed that can assess microbial levels in poultry processing waters within 15 min. A study was conducted to determine the effectiveness of this test for examining scald, prechill, and chill tank waters. The results showed that the modified ATP bioluminescence method gave results comparable to plate counts. The microbial levels were dependent on the tank and the time of sampling. The highest microbial levels were detected in the scald tank. In all three tanks, the microbial levels increased over time during the day. PMID- 7862607 TI - The influence of extended posthatch holding time and placement density on broiler performance. AB - Extended posthatch holding (in the hatcher) has been reported to dehydrate chicks, reduce broiler performance, and depress immune response. Nevertheless, some commercial hatcheries are increasing incubation time in an attempt to minimize possible bacterial contamination of incompletely healed navels. The objectives of this study were to determine the effects of posthatch holding on broiler performance and the effects of bird density and additive stress on performance and immune response. Twelve hundred broiler eggs (58 to 70 g) were incubated. Chicks were removed from the hatcher after 528 h of incubation, banded, and weighed. Half of the chicks were returned to the hatcher for an additional 24 h (HELD). Both hatcher treatments were placed at two densities (.07 and .12 m2 per bird). Individual BW were taken at 21 and 43 d of placement and 43 d of age. The HELD chicks weighed significantly less than controls at time of placement. At 21 d postplacement the HELD broilers were significantly heavier than controls, but were similar by 43 d. Total feed conversion was not affected in the HELD treatment, but birds in the .07 m2 per bird density were less efficient in terms of total feed conversion. Chick holding time and density seemed to affect antibody titers at 5 wk. Although holding chicks in the hatcher for 24 h did not clinically dehydrate chicks or affect performance, it decreased immune response. In addition to less efficient growth, birds in the more crowded pens had depressed immune response. PMID- 7862608 TI - Development and characterization of chicken-chicken B cell hybridomas secreting monoclonal antibodies that detect sporozoite and merozoite antigens of Eimeria. AB - Chicken-chicken B cell hybridomas that secrete monoclonal antibodies (mAb) detecting antigens located at the anterior tip of the sporozoites of Eimeria acervulina have been produced. Peripheral blood lymphocytes (PBL) obtained from chickens infected with E. acervulina were fused with a thymidine-kinase deficient (TK-) chicken B cell line. Hybridomas secreting mAb binding to the sporozoite antigens of E. acervulina were selected using an ELISA. Two stable hybridomas, whose mAb were designated as P11 and P66, respectively, were obtained and their binding characteristics were assessed. The mAb P11 detects the sporozoite but not the merozoite antigens of E. acervulina and Eimeria tenella. The P66 mAb recognizes a cross-reactive antigen of sporozoite and merozoite of E. acervulina but not E. tenella. Flow cytometric analysis of the hybridomas secreting the P11 and P66 mAb showed expression of surface IgM and IgG, respectively. Western blot analysis under reducing conditions showed that mAb P11 recognized a sporozoite protein of 43 kDa. Both mAb recognized antigens located at the anterior end of the sporozoites by indirect immunofluorescence staining. This study shows the development of chicken B cell hybridomas that secrete coccidia-specific mAb. PMID- 7862609 TI - The effects of adrenocorticotropic hormone and heat stress on the distribution of lymphocyte populations in immature male chickens. AB - This study investigated the effects of heat stress and adrenocorticotropic hormone (ACTH) on the distribution of lymphocyte populations. Two experiments were conducted; each used 12-wk-old Cornell K-strain male chickens. In Experiment 1, birds were exposed to a temperature of 35 C, 6 h/d for 5 d and control birds were maintained at 24 C. In Experiment 2, birds received daily i.m. injections of 50 IU/kg body weight of ACTH for 5 d and control birds received .9% saline. On Day 6, blood and spleens were collected and lymphocytes were isolated. Indirect immunofluorescent labeling of lymphocytes were performed to detect B lymphocytes, CD4+ cells, and CD8+ cells. Neither ACTH injection nor heat stress affected percentages of B lymphocytes in the blood or the spleen. The CD4+ cells decreased significantly in the blood of ACTH-injected and heat-stressed birds and significantly increased in the spleens of heat-stressed birds. The CD4+ cells in the spleens of ACTH-injected birds did not differ from controls. The CD8+ cells significantly declined in the blood following both ACTH injection and heat stress and significantly increased in the spleen of the ACTH-injected birds but did not differ from controls in the heat-stressed birds. These results indicate that stress factors lead to redistribution of different lymphocyte populations. PMID- 7862610 TI - Production variables and nutrient retention in single comb White Leghorn laying pullets fed diets supplemented with direct-fed microbials. AB - Two experiments were carried out for six and seven 28-d periods, respectively, with DeKalb XL Single Comb White Leghorn laying pullets to ascertain the effect of feeding 1,100 mg Lactobacillus (Lacto)/kg diet (ppm) and 2,200 ppm Lacto diets, and the supplementation of these diets with 1 and 3% fat, on layer performance and nitrogen, calcium, and phosphorus retention. The dietary treatments were corn-soybean meal (C-S) control, C-S plus condensed cane molasses solubles (CCMS)-1,100 ppm Lacto (4.4 x 10(7) cfu/mg Lacto), and C-S plus CCMS 2,200 ppm Lacto (8.8 x 10(7) cfu/mg Lacto) without fat (Experiment 1) and without and with 1 and 3% supplemental fat to each Lacto level (Experiment 2). In both experiments, layers fed the 1,100 ppm Lacto diets had better (P < .05) hen-day production, daily feed consumption, egg mass, egg weight, egg size, and feed conversion than layers fed diets without Lacto. Egg mass, interior egg quality, and feed conversion (Experiment 1), mean body weight gains, and nitrogen, calcium, and phosphorus retention (Experiment 2) were further improved (P < .05) with feeding 2,200 ppm Lacto diets. Feeding Lacto diets with 1% fat provided (P < .05) larger eggs and better (P < .05) nitrogen and phosphorus retention, whereas 3% fat decreased (P < .05) feed consumption and nutrient retention and improved (P < .05) feed conversion and body weight gain. Positive correlations between Lacto diets and nitrogen and calcium retentions, daily feed consumption, and egg size were observed. Feeding 1,100 ppm Lacto diets to layers stimulated appetite and improved egg production, egg mass, egg weight, egg size, and feed conversion. Addition of fat to Lacto diets reduced daily feed consumption and provided better feed conversion, egg masses, egg sizes, body weight gains, and nutrient retentions. PMID- 7862611 TI - Performance of single comb White Leghorn layers fed corn-soybean meal and barley corn-soybean meal diets supplemented with a direct-fed microbial. AB - An experiment was conducted with Single Comb White Leghorn (SCWL) layers to determine the effect of feeding either corn-soybean meal (C-S) or barley-corn soybean meal (B-C-S) diets with or without condensed cane molasses solubles (CCMS) or with or without CCMS-1,100 mg Lactobacillus (Lacto)/kg (ppm) diet on performance, nutrient retentions, digesta passage rate, and histological changes of the gastrointestinal (GI) tracts. Six dietary treatments were fed for eight 28 d periods and consisted of C-S (control), C-S + CCMS, C-S + CCMS-1,100 ppm Lacto (4.4 x 107 cfu/mg Lacto), B-C-S (control), B-C-S + CCMS, and B-C-S + CCMS-1,100 ppm Lacto. The CCMS served as the carrier for the Lacto, and the CCMS-Lacto premix (55 g Lacto/kg) was incorporated at 2% of the diet. Lactobacillus supplementation in C-S diets improved (P < .05) egg weight, egg mass, egg size, and body weight gains, and in B-C-S diets improved body weight gains. There were no differences in feed consumption, feed conversion, internal egg quality, and egg specific gravity among the dietary treatments. Passage rates of digesta were increased (P < .05) when either C-S or B-C-S layer diets were supplemented with Lacto. Lactobacillus supplementations of the C-S and B-C-S diets increased (P < .05) fat and calcium, and fat, phosphorus, copper, and manganese retentions, respectively. Increased cellularity of Peyer's patches in the ileum indicated a stimulation of the mucosal immune system that responds to antigenic stimuli by secreting immunoglobulin (IgA). PMID- 7862612 TI - The use of feed restriction for improving reproductive traits in male-line large white turkey hens. 1. Growth and carcass characteristics. AB - The influence of feed allowance during rearing was investigated in male-line Large White breeder hens. A flock of 200 poults was reared from 4 to 28 wk of age under four treatments as follows: full-fed controls (FF), low-protein diet (12% CP from 12 to 28 wk; LP), and reduced BW (10 or 20% lower BW than FF; R10 and R20). At photostimulation (28 wk), all birds consumed a commercial breeder diet ad libitum for the remainder of the study (48 wk of age). Body weight differed among treatments during most of rearing. The LP birds were similar in BW to the R10 birds at 28 wk of age. By 40 wk of age, growth curves of all treatments became similar, with the R20 group having lower BW. Feed restriction reduced frame size during rearing. Flock uniformity in the R10 and R20 treatment hens was reduced during rearing, but improved early in the breeder period. Feed restriction reduced breast muscle and abdominal fat pad weight early in lay, except for the LP group. Liver lipid content increased throughout the breeder period. Changes in liver weight followed the pattern of BW changes. Total carcass protein content changes in time reflected breast muscle mass changes. In R20 hens, carcass lipid content was reduced and protein content increased. Sexual maturity was delayed in the R20 hens. Body weight at first egg was negatively correlated with settable egg production (r = -.37, P < or = .0015). The R20 treatment is recommended for male-line turkey breeder hen candidates during rearing. PMID- 7862613 TI - Digestible lysine requirement of male and female broiler chicks during the period three to six weeks posthatching. AB - Experiments were conducted to determine the dietary digestible lysine requirement of male and female broilers (Ross x Ross) during the period 22 to 43 d posthatching. An amino acid-fortified basal diet containing corn, feather meal, and soybean meal as intact protein sources provided .63% total lysine, 20% CP, and 3,200 kcal MEn/kg. The basal diet contained .51% true digestible lysine as determined with a precision-fed cecectomized adult cockerel assay. Growth rate and feed efficiency of birds fed the basal diet fortified with a surfeit level of L-lysine were equal to those of birds fed a methionine-supplemented corn-soybean meal positive control diet (20% CP; 3,200 kcal MEn/kg). Graded levels of synthetic L-lysine (0, .1, .2, .3, .4, .5, .6%) were added to the basal diet to produce growth response curves. Subjecting the growth data to broken-line analysis indicated that the digestible lysine requirement for maximum body weight gain was .85% for males and .78% for females. The requirement for optimum feed efficiency was higher: .89% for males and .85% for female broilers. Breast meat (Pectoralis major) yield increased quadratically in response to lysine addition, and the responses suggested that the lysine requirement for maximal breast yield was not greatly different from that predicted from the feed efficiency data. Abdominal fat (percentage of live body weight) increased from the first to the second increment of lysine, but it then declined as lysine level was increased further. PMID- 7862614 TI - Plasma growth hormone and prolactin response to FK 33-824, a synthetic opioid agonist, in broiler chickens. AB - A synthetic opioid agonist, FK 33-824 ([D-Ala2,N-Me-Phe4,Met-(O)5-ol]- enkephalin), was administered intramuscularly at levels of 0, 1, 25, or 625 micrograms/kg of body weight to 4-wk-old Arbor Acres x Arbor Acres broiler cockerels. All levels of FK 33-824 caused the birds to be sedated, with the highest dose causing deep sedation over the 240-min test period. A significant time by treatment interaction was seen for plasma growth hormone (GH). At 30 min after treatment, a significant increase in GH occurred, but this transitory increase returned to control levels at 60 min. A secondary GH peak was observed in the 240-min samples from cockerels given the 625 micrograms/kg dose. Significant treatment and time effects and a time by treatment interaction were seen in the plasma prolactin (PRL) response to FK 33-824. Prolactin was increased at 30 and 60 min after treatment with 1 microgram/kg, whereas higher doses seemed to suppress PRL concentrations. Over the 240-min experimental period, PRL concentrations tended to increase in all treatments except in the treatment with the lowest FK 33-824 dose, but the largest transitory increase was observed at 240 min in the birds given the 625 micrograms/kg dose. These results suggest that FK 33-824 affected GH and PRL secretion in chickens in a manner different from other opioid agonists. This difference was probably due to the ability of FK 33 824 to bind to multiple opiate receptors, with the highest affinity for mu receptors and lesser affinity for delta receptors, whereas other opioids have high affinity for delta receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862615 TI - No association found between the ascites syndrome in broilers and feeding of oats contaminated with deoxynivalenol up to thirty-five days of age. AB - This study investigated the possible effects of feeding broilers oats that were naturally contaminated with deoxynivalenol (DON) on development of the ascites syndrome. Four groups of 240 birds were fed complete feed mixtures with graded amounts of contaminated oats giving from .1 (control) to 3.4 mg DON/kg feed. The broiler chickens were 1 d old at start of trial and were slaughtered at Day 35. Performance and carcass quality were not affected by the mycotoxin in the diets. No clinical signs of ascites or occurrence of other treatment-related lesions were detected. PMID- 7862616 TI - Effect of injection site on cutaneous basophil hypersensitivity response to phytohemagglutinin. AB - Cutaneous basophil hypersensitivity response to phytohemagglutinin (PHA) is frequently used as a measure of cell-mediated immune response in chickens. Several anatomical sites have been used to measure this response. No correlation between response level at different sites, however, has been reported. This study compares responses to PHA by using two different injection sites (wing web and interdigital skin of the foot) in White Leghorn chickens. Response at each individual site was comparable whether the bird received a PHA injection at that site alone or at both sites. Correlations between responses at the two sites were not different from zero [-.1733 (P = .44)]. These data indicate that caution must be exercised in comparing cell-mediated immune responses when different PHA injection sites have been used to assess response. PMID- 7862617 TI - The effects of supplementing diets with Saccharomyces cerevisiae var. boulardii on male poult performance and ileal morphology. AB - This study determined the effects of three levels of supplemental yeast of Saccharomyces cerevisiae var. boulardii (SCB) on commercial male poult performance and ileum morphology. One hundred and sixty Nicholas poults were randomly assigned to 16 battery cages (10 poults per cage, 4 cages per diet) from 1 to 21 d of age (DOA). Poults were fed diets (26% CP) consisting of corn-soybean (CS, control), CS + .01% SCB, CS + .02% SCB, and CS + .06% SCB. At 21 DOA, 30 poults fed the CS and CS + .02% SCB diets (from 1 to 21 DOA) were randomly selected within each diet, placed in 1 of 6 cages (5 poults per cage, 3 cages per diet), and fed their respective diet to 35 DOA. Body weights and feed consumptions (FC) were measured at 21 and 35 DOA and morphological comparisons of ileal tissues were conducted at 35 DOA. Increased BW (P < .004) at 7, 14, and 21 DOA were observed for poults fed diets containing SCB at .01, .02, and .06% of the diet. No dietary differences (P > .05) were observed in FC or feed:gain ratios from 1 to 21 DOA. Increased (P < .03) BW were maintained from 21 to 35 DOA for poults fed .02% SCB, whereas no dietary differences (P > .05) in FC or feed:gain were observed. Histological examination of ileal sections from poults (35 DOA) fed the CS and CS + .02% SCB diets revealed a decrease (P < .04) in the number of goblet cells per millimeter of villus height and a decreased (P < .02) crypt depth in poults receiving .02% SCB. No dietary differences (P > .05) were observed for either villus height or width. PMID- 7862618 TI - Re-evaluation of a biguanide, metformin: mechanism of action and tolerability. AB - Metformin is a biguanide antidiabetic medication, that has been in use for over 30 years. Its mechanism of action, unknown until a few years ago, is now linked to an improved peripheral sensitivity to insulin, through a stimulated tissue glucose uptake by a transporter linked system. Interest in metformin has been revived by the recent observation of a specific activity of this agent on some of the major traits of the so called 'polymetabolic syndrome' (or 'syndrome X'), characterized by: insulin resistance, hypertriglyceridemia, hypertension and reduced fibrinolytic activity. Metformin, in studies examining one or more of these, has been shown, possibly through its peripheral insulin sensitizing mechanism, to correct most of the major symptoms characterizing this insulin resistance syndrome. Metformin, similarly to the other biguanide phenformin, has been rated as potentially dangerous, because of the possible induction of lactic acidosis, in some cases with a fatal outcome. Metformin is, however, associated with a very low incidence of lactic acidosis because, differently from phenformin, it does not undergo liver metabolism and, as a consequence, there are no high-risk groups, displaying an impaired metabolic handling. In this review, in addition to an overall evaluation of the more recent data on the mechanism of action and clinical use of metformin, a detailed clinical analysis of all published cases of lactic acidosis is provided. These data indicate that the risk in metformin use is negligible, provided that care is taken when prescribing the drug to patients with suspected clinical risks of lactic acidosis. PMID- 7862619 TI - No documentable role for xanthine oxidase in the pathogenesis of hepatic in vivo ischaemia/reperfusion injury. AB - An investigation was made into the possible involvement of the enzyme xanthine oxidase (XO) (EC 1.1.3.22), both reversible (XOrev) and irreversible (XOirr), in damage observed after short-term in vivo hepatic ischaemia/reperfusion (60 or 120 min I and 15 min R) in fasted rats with: (i) a physiological content of XO (25%); and (ii) higher XO percentage (45%). In the latter the hepatic XO physiological percentage was increased by diethylmaleate treatment (300 mg kg-1) that depleted the cytosolic glutathione (GSH) to 14% of the controls. It was shown that, in animals with physiological content of XO, 60 and 120 min of hepatic ischaemia followed by 15 min reperfusion results in decreased GSH levels, and significantly increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels, without any modification of either the percentages of XO (XOirr and XOrev) or the hepatic thiobarbituric acid reactive substances (TBARS). Sixty minutes of ischaemia/reperfusion in rats with the higher XO level and lower hepatic GSH content led to further conversion of XDH to XOrev, with no increase in XOirr. In addition, the ALT and AST serum levels in these animals rose to the same extent as in normal rats after 120 min ischaemia and 15 min reperfusion, this extent being observed to be associated with a moderate increase in thiobarbituric acid reactive substances (TBARS). However, the administration of allopurinol, at a dose of 50 mg kg-1, which almost completely inhibits XO activity, did not lead to any decrease in liver damage or TBARS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862620 TI - The effects of doxazosin on plasma lipid and lipoprotein levels in hypertensive patients. AB - Plasma lipid and lipoprotein levels were evaluated in 27 adults with essential hypertension at four different periods during a 12-month treatment with doxazosin. Mean plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), triglyceride (TG), very low density lipoprotein-cholesterol (VLDLC) and the LDLC/HDLC ratio were significantly reduced following doxazosin therapy. The HDLC/C ratio was found to be increased, while mean high density lipoprotein cholesterol (HDLC) level remained unchanged at 3, 6, 9 and 12 months of measurement after doxazosin treatment. Our data showed that the duration of doxazosin treatment did not influence the observed favourable lipid changes; but TC and LDLC appear to be the lipid fractions most affected by doxazosin in all the patients. In order to determine the possible factors responsible for the lipid-altering actions of doxazosin treatment, we observed beneficial lipid and lipoprotein changes in both the male and female subpopulations of patients with a slightly higher magnitude in the females. The dosage of doxazosin was, however, found to have no influence on the lipid-altering actions; a further study was therefore recommended. PMID- 7862621 TI - Antithrombotic activity of nicardipine in spontaneously hypertensive rats. AB - Calcium metabolism appears to be altered in human and experimental hypertension, which represents an important risk factor for thrombotic events. We investigated the possible effect of the calcium antagonist nicardipine on a model of experimental venous thrombosis in spontaneously hypertensive rats (SHR). Thrombus formation was highly enhanced in SHR with respect to normotensive Wistar Kyoto rats (WKY). Nicardipine, when administered orally (10 mg kg-1) at a single dose or once a day for three days, completely counteracted the increase in thrombus size caused by hypertension. Furthermore, a significant rise in prostacyclin production from aortic tissue [19.2 +/- 1.5 vs 13.2 +/- 2.4 ng (mg dry tissue) 1], associated with a fall in thromboxane A2 release from activated platelets (328.3 +/- 74.6 vs 705.0 +/- 88.1 ng ml-1), was observed in nicardipine-treated SHR. Plasma triglyceride and free fatty acid levels were also lowered by drug administration. Our results suggest that the actions of nicardipine on calcium metabolism result in antithrombotic effect through an increased availability of vasodilating eicosanoids in vessel walls and through a reduced amount of prothrombotic agents (thromboxane, free fatty acids). PMID- 7862622 TI - Effect of DL alpha-lipoic acid in glyoxylate-induced acute lithiasis. AB - Glyoxylic lithiasis by acute intoxication with sodium glyoxylate, significantly raised the levels of renal tissue calcium and oxalate which has been reflected simultaneously in their urinary levels. Administration of DL alpha-lipoic acid lowered the oxalate levels in the kidney and urine. Sodium glyoxylate administration resulted in enhanced liver glycollate oxidase activity, the major enzyme in endogenous oxalate synthesis. DL alpha-lipoic acid decreased glycollate oxidase activity but did not have any effect on lactate dehydrogenase. The possibility of regulating oxalate metabolism in glyoxylic lithiasis with the use of DL alpha-lipoic acid, by way of inhibiting liver glycollate oxidase, looks attractive. PMID- 7862623 TI - Hepatitis B virus transactivator protein X interacts with the TATA-binding protein. AB - Several viral transcriptional activators have been shown to interact with the basal transcription factor TATA-binding protein (TBP). These associations have been implicated in facilitating the assembly of the transcriptional preinitiation complex. We report here that the hepatitis B virus protein X (pX) specifically binds to TBP in vitro. While truncations of the highly conserved carboxyl terminus of TBP abolished this binding, amino-terminal deletions had no effect. Deletion analysis suggests that a domain consisting of 71 aa in the highly conserved carboxyl-terminal region of TBP is necessary for its interaction with pX. The minimal region in pX sufficient for its interaction with TBP includes aa 110-143. Furthermore, TBP from phylogenetically distinct species including Arabidopsis thaliana, Saccharomyces cerevisiae, Drosophila melanogaster, and Solanum tuberosum (potato) bound to pX. The pX-TBP interaction was inhibited in the presence of nonhydrolyzable analogs of ATP, suggesting a requirement for ATP. These results provide an explanation for the promiscuous behavior of pX in the transactivation of a large repertoire of cellular promoters. This study further implicates a fundamental role for pX in modulating transcriptional regulatory pathways by interacting with the basal transcription factor TBP. PMID- 7862624 TI - Single cell monitoring of growth arrest and morphological changes induced by transfer of wild-type p53 alleles to glioblastoma cells. AB - Mutation of the p53 tumor suppressor gene is one of the earliest identified genetic lesions during malignant progression of human astrocytomas. To assess the functional significance of these mutations, wild-type (WT) p53 genes were introduced into glioblastoma cell lines having mutant, WT, or null endogenous p53 alleles. Populations of cells with mutant or null endogenous p53 alleles and exogenous WT p53 were spontaneously selected in culture for cells expressing only mutant p53 or no p53, which then displayed a growth and tumorigenic phenotype identical to the parental cells. To determine the phenotypic consequences of WT p53 expression before the occurrence of mutations, we developed a single cell assay to monitor WT p53-dependent transcription activity. Transfer and expression of exogenous WT p53 genes to cells with endogenous mutant or deleted, but not WT, p53 alleles caused growth arrest and morphological changes, including increased cell size and acquisition of multiple nuclei. This supports the hypothesis that genetic lesions of the p53 gene play an important role in the genesis of astrocytomas. Furthermore, the high sensitivity of the episomal single cell reporter strategy developed here has potential clinical applications in the rapid screening of patients for germ-line mutations of the p53 gene or any other gene with known targets for transcriptional transactivation. PMID- 7862625 TI - Rearrangements in the genome of the bacterium Salmonella typhi. AB - We have determined the genomic map of the bacterium Salmonella typhi Ty2, the causal organism of typhoid fever, by using pulsed-field gel electrophoresis. Digestion of the Ty2 genome with endonucleases Xba I, Bln I, and Ceu I yielded 33, 26, and 7 fragments, respectively, that were placed in order on a circular chromosome of 4780 kb. Transposon Tn10 was inserted in specific genes of Salmonella typhimurium and transduced into S. typhi, and thus, the positions of 37 S. typhi genes were located through the Xba I and Bln I sites of the Tn10. Gene order on chromosomes of Escherichia coli K-12 and S. typhimurium LT2 is remarkably conserved; however, the gene order in S. typhi Ty2 is different, suggesting it has undergone major genomic rearrangements during its evolution. These rearrangements include inversions and transpositions in the 7 DNA fragments between the seven rrn operons for rRNA (postulated to be due to homologous recombination in these rrn genes), another inversion that covers the replication terminus region (resembling inversions found in other enteric bacteria), and at least three insertions, one as large as 118 kb. Partial digestion of genomic DNA with the intron-encoded endonuclease I-Ceu I, which cuts only in rrn genes, shows chromosomal rearrangements, apparently due to homologous recombination in the rrn genes, that were detected in all wild-type strains of S. typhi tested. These rearrangements may have been selected to compensate for the insertions that otherwise would have altered the locations of genes with respect to the origin and terminus of replication. These observations are relevant to our view of the evolution of the bacterial genome and may be significant in the virulence of S. typhi. PMID- 7862626 TI - Gene therapy for hemophilia A: production of therapeutic levels of human factor VIII in vivo in mice. AB - Continuous delivery of factor VIII (FVIII) protein in hemophiliacs by gene therapy will represent a major clinical advance over the current practice of infrequent administration of purified FVIII. Conceptually, retroviral vectors that can permanently insert the FVIII gene into the DNA of the host cell appear the most suitable vehicles for this specific purpose. However, most retroviral vector systems have shown a poor performance in the production of FVIII from primary cells in vitro and in vivo. Here we report the retroviral-mediated gene delivery of a B-domain-deleted human FVIII by using the MFG vector system. This vector permitted efficient transduction of the majority of the primary cells in culture without the use of a selectable marker. High levels of FVIII were produced by various transduced primary cells in vitro. Upon transplantation of primary fibroblasts into mice, therapeutic levels of FVIII in the circulation were obtained for > 1 week. The capacity of primary cells to deliver the FVIII into the circulation was strongly dependent on the site of implantation. These results represent a major step forward in development of gene therapy for treating hemophilia A. PMID- 7862627 TI - Characterization of the genomic breakpoint and chimeric transcripts in the EWS WT1 gene fusion of desmoplastic small round cell tumor. AB - Desmoplastic small round cell tumor is a recently recognized distinctive tumor shown to be associated with a recurrent translocation, t(11;22)(p13;q12), and rearrangement of the genes for Ewing sarcoma (EWS) and Wilms tumor (WT1). A genomic DNA fragment containing the EWS-WT1 gene fusion has been isolated from a desmoplastic small round cell tumor, and the breakpoint has been characterized. The breakpoints involve the intron between EWS exons 7 and 8 and the intron between WT1 exons 7 and 8. Chimeric transcripts corresponding to the fusion gene were detected in four of six cases studied. Analysis of these transcripts show an in-frame fusion of RNA encoding the amino-terminal domain of EWS to both alternatively spliced forms of the last three zinc fingers of the DNA-binding domain of WT1. Desmoplastic small round cell tumor represents the third tumor type associated with translocation of EWS and the first tumor associated with consistent translocation of WT1. The chimeric products are predicted to modulate transcription at WT1 target sites and contribute to development of this unique tumor. PMID- 7862628 TI - Application of chiral gas chromatography with electroantennographic detection to the determination of the stereochemistry of a cockroach sex pheromone. AB - The coupling of an electroantennographic detector to a chiral capillary gas chromatographic system provides a highly sensitive technique for the determination of pheromone stereochemistry. Electronic modification of the usual electroantennographic detector enables the detector to respond to the relatively broad peaks produced by chiral gas chromatographic systems. By using this methodology, supellapyrone, a female sex pheromone of the brownbanded cockroach Supella longipalpa (Orthoptera: Blattellidae), is shown to be 5-(2'R,4'R dimethylheptanyl)-3-methyl-2H-pyran-2-one. PMID- 7862629 TI - Structure, stereochemistry, and thermal isomerization of the male sex pheromone of the longhorn beetle Anaglyptus subfasciatus. AB - Male-released sex pheromone constituents of the longhorn beetle Anaglyptus subfasciatus (Coleoptera: Cerambycidae) are identified by GC-MS and GC-Fourier transform infrared as a 7:1 molar mixture of 3-hydroxy-2-hexanone and 3-hydroxy-2 octanone. These two compounds undergo thermal isomerization during GC analyses to give the corresponding 2-hydroxy-3-alkanones. Comparison of GC retention times of the natural products with those of synthesized enantiomerically pure compounds revealed that both semiochemicals have (R)-stereochemistry. These absolute configurations were confirmed by comparisons of the (R) methoxy(trifluoromethyl)phenylacetic acid esters of insect-derived and synthetic samples. PMID- 7862630 TI - Subunit functional studies of NAD(P)H:quinone oxidoreductase with a heterodimer approach. AB - NAD(P)H:quinone oxidoreductase (NQOR; EC 1.6.99.2) is a homodimeric enzyme which catalyzes the reduction of quinones, azo dyes, and other electron acceptors by NADPH or NADH. To pursue subunit functional studies, we expressed a wild type/mutant heterodimer of NQOR in Escherichia coli. The wild-type subunit of the heterodimer was tagged with polyhistidine and the other subunit contained a His 194-->Ala mutation (H194A), a change known to dramatically increase the Km for NADPH. This approach enabled us to efficiently purify the heterodimer (H194A/HNQOR) from the homodimers by stepwise elution with imidazole from a nickel nitrilotriacetate column under nondenaturing conditions. The composition of the purified heterodimer was confirmed by SDS and nondenaturing polyacrylamide gel electrophoresis and immunoblot analysis. The enzyme kinetics of the purified heterodimer were studied with two two-electron acceptors, 2,6-dichloroindophenol and menadione, and a four-electron acceptor, methyl red, as the substrates. With two-electron acceptors, the Km(NADPH) and Km(NADH) values of the heterodimer H194A/HNQOR were virtually identical to those of the wild-type homodimer, but the kcat-(NADPH) and kcat(NADH) values were only about 50% those of the wild-type homodimer. With the four-electron acceptor, the Km and kcat values of H194A/HNQOR for NADPH and NADH were similar to those of the low-efficiency mutant homodimer. These results suggest that the subunits of NQOR function independently with two electron acceptors, but dependently with a four-electron acceptor. This heterodimer approach may have general applications for studying the functional and structural relationships of subunits in dimeric or oligomeric proteins. PMID- 7862631 TI - Purification and characterization of recombinant human p50csk protein-tyrosine kinase from an Escherichia coli expression system overproducing the bacterial chaperones GroES and GroEL. AB - An Escherichia coli expression system overproducing the bacterial chaperones GroES and GroEL was engineered and has been successfully used to produce large quantities of the recombinant human protein-tyrosine kinase p50csk. The co overproduction of the two chaperones with p50csk results in increased solubility of the kinase and allows purification of milligram amounts of active enzyme. Analysis of the purified protein by SDS/polyacrylamide gel electrophoresis reveals a single band with an apparent molecular mass of 50 kDa, indicating that recombinant human p50csk has been purified to near homogeneity. The purified enzyme displays tyrosine kinase activity as measured by both autophosphorylation and phosphorylation of exogenous substrates. Biochemical properties, including in vitro substrate specificity and enzymatic characteristics of the enzyme, have been assessed and compared with those of members of the Src family of protein tyrosine kinases. Results indicate that p50csk and p56lck have different substrate specificities and that p50csk and p60c-src have similar kinetic parameters. The successful production and purification of an enzymatically active form of p50csk will enable further characterization of this important kinase and allow clarification of its physiological role. In addition, the results suggest that the approach described may be generally applicable to improve the solubility of recombinant proteins which otherwise are produced in an insoluble form in E. coli. PMID- 7862632 TI - Contributions made by individual methylation sites of the Escherichia coli aspartate receptor to chemotactic behavior. AB - To determine the extent to which chemotactic behavior depends on methylation at multiple sites, chemotaxis assays were performed on bacteria that expressed mutant aspartate receptors in which methylation site residues were mutated from glutamate to aspartate. It was found that chemotaxis was impaired when methylation sites were mutated and that the effect on chemotaxis of mutating a rapidly methylated site was more severe than the effect of mutating a less rapidly methylated site. Expression of mutant receptors in a wild-type strain interfered with chemotaxis to only a minor extent. In vivo methylation assays showed that the chemotactic defects of most mutants could be explained by the decreased rates at which methylation levels increased in response to aspartate. PMID- 7862633 TI - Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I. AB - The human T-cell leukemia virus type I Tax protein trans-activates several cellular genes implicated in T-cell replication and activation. To investigate its leukemogenic potential, Tax was targeted to the mature T-lymphocyte compartment in transgenic mice by using the human granzyme B promoter. These mice developed large granular lymphocytic leukemia, demonstrating that expression of Tax in the lymphocyte compartment is sufficient for the development of leukemia. Furthermore, these observations suggest that human T-cell leukemia virus infection may be involved in the development of large granular lymphocytic leukemia. PMID- 7862634 TI - Identification of kappa opioid receptors in the immune system by indirect immunofluorescence. AB - A method to visualize the kappa opioid receptor is described that uses a high affinity fluorescein-conjugated opioid ligand and indirect immunofluorescence with the phycoerythrin fluorophore to amplify the signal. The mouse thymoma cell line R1E/TL8x.1.G1.OUAr.1 (R1EGO), which expresses the kappa 1 but not mu or delta opioid receptors, was used as a positive control for fluorescence labeling. A fluorescein isothiocyanate-conjugated arylacetamide (FITC-AA) compound displaying high affinity for the kappa opioid receptor was synthesized. R1EGO cells were incubated with FITC-AA, in the absence or presence of the kappa selective opioid antagonist nor-binaltorphimine (nor-BNI) as a competitor. By using fluorescence microscopy and flow cytometry, incubation of R1EGO cells with FITC-AA alone was not sufficient for the detection of specific staining of the kappa opioid receptor. To amplify the FITC-AA fluorescence, the fluorescein served as a hapten for subsequent antibody detection. R1EGO cells were incubated with FITC-AA, followed by biotinylated rabbit anti-fluorescein IgG and extravidin conjugated R-phycoerythrin. By using this approach, R1EGO cells were stained with phycoerythrin-amplified FITC-AA, and the staining was displaced with nor-BNI. Flow cytometry showed that titrations of both FITC-AA and nor-BNI produced saturable concentration-dependent changes in the median phycoerythrin fluorescence intensity, with optimal staining at 30 microM FITC-AA. Up to 80% of the fluorescence above background was inhibited by nor-BNI. Freshly isolated thymocytes from C57BL/6ByJ mice also showed nor-BNI-sensitive staining with the FITC-AA amplification. This sensitive method of indirect phycoerythrin immunofluorescence can be used to amplify any fluorescein-conjugated opioid ligand for the detection of opioid receptors. PMID- 7862635 TI - Oxidation of gamma II-crystallin solutions yields dimers with a high phase separation temperature. AB - Aqueous solutions of the bovine eye lens protein gamma II (or gamma B)-crystallin at neutral pH show a gradual increase in phase separation temperature, Tph, when allowed to stand for several weeks at room temperature without reducing agents. In a typical experiment, the Tph of the protein solution (218 mg/ml) increases from 2.5 +/- 1 degree C to 32.5 +/- 1 degree C after 21 days, and a new protein species, gamma IIH, is formed. The Tph of pure gamma IIH is at least 40 degrees C higher than that of pure gamma II. The average apparent hydrodynamic radius is 36 A for gamma IIH compared to 26 A for gamma II. The molecular mass of gamma IIH is approximately 41.5 kDa compared to 20 kDa for native gamma II. Therefore, gamma IIH is probably a dimer of gamma II crystallin. gamma IIH has a lower thiol content than gamma II and is not formed in the presence of dithiothreitol. We conclude that gamma IIH is a thiol oxidation product of gamma II-crystallin and is a dimer containing an intermolecular disulfide crosslink. Thus, some oxidative modifications of protein thiol groups lead to an increase in net attractive interactions between proteins. As a result, Tph increases and protein aggregates are formed. These two microscopic changes produce the increased light scattering associated with lens opacification. PMID- 7862636 TI - The canine betaine gamma-amino-n-butyric acid transporter gene: diverse mRNA isoforms are regulated by hypertonicity and are expressed in a tissue-specific manner. AB - The Na(+)- and Cl(-)-coupled betaine transporter, designated BGT1, a member of the neurotransmitter transporter gene family, is responsible for accumulation of betaine in hypertonic Madin-Darby canine kidney (MDCK) cells and presumably in the hypertonic renal medulla. The canine gene for the betaine gamma-amino-n butyric acid transporter has been cloned and analyzed. The gene extends over 28 kb and consists of 18 exons. The 5' end of the gene has three alternative first exons (1A, 1B, and 1C+D). Analysis of BGT1 mRNA revealed that there is considerable divergence in the 5' untranslated sequence resulting from three different 5' end motifs (A, B, and C) followed by an alternative motif (D) as well as two internal acceptor sites for splicing. Eight kinds of BGT1 mRNA were classified into three types (A, B, and C) according to the 5' end sequence. Northern blot analysis using probes specific for the A, B, or C motif revealed that hypertonicity induces all three types in MDCK cells. Reverse transcription and polymerase chain reaction showed that each type was expressed in a tissue specific manner. Primer extension and/or RNase protection assays as well as transfection assays into MDCK cells demonstrated that exons 1A, 1B, and 1C+D have independent transcription initiation sites under control of independent promoters. Diverse mRNA isoforms are regulated by hypertonicity and are expressed in a tissue-specific manner. PMID- 7862637 TI - Platelet-derived growth factor triggers translocation of the insulin-regulatable glucose transporter (type 4) predominantly through phosphatidylinositol 3-kinase binding sites on the receptor. AB - Insulin is the only known hormone which rapidly stimulates glucose uptake in target tissues, mainly by translocation to the cell surface of the intracellular insulin-regulatable glucose transporter (glucose transporter type 4, GLUT4). We have developed a cell line for direct, sensitive detection of GLUT4 on the cell surface. We have suggested that insulin-activated phosphatidylinositol (PI) 3 kinase may be involved in the signaling pathway of insulin-stimulated GLUT4 translocation. We report that platelet-derived growth factor (PDGF), which stimulates PI 3-kinase activity, triggers GLUT4 translocation in Chinese hamster ovary (CHO) cells stably overexpressing the PDGF receptor and in 3T3-L1 mouse adipocytes. Using mutant PDGF receptors that cannot bind to Ras-GTPase-activating protein, phospholipase C-gamma, and PI 3-kinase, respectively, we obtained evidence that PI 3-kinase binding sites play a key role in the signaling pathway of PDGF-stimulated GLUT4 translocation in the CHO cell system. PMID- 7862638 TI - Internal and interfacial dielectric properties of cytochrome c from molecular dynamics in aqueous solution. AB - The dielectric properties of proteins are central to their stability and activity. We use the Frohlich-Kirkwood theory of dielectrics to analyze two 1-ns molecular dynamics simulations of ferro- and ferricytochrome c in spherical droplets of 1400 water molecules. Protein and solvent are idealized as a series of concentric, spherical, dielectric media. Analysis results depend strongly on the treatment of the charged protein side chains at the protein/solvent interface. If charged side chains are viewed as part of the protein medium, then the protein dipole fluctuations are dominated by large, mutually uncorrelated, anisotropic, motions of the charged side chains. It is then incorrect to view the protein region as a single, homogeneous dielectric material. If one does take this view, estimates of the protein "dielectric constant" vary from 16 to 37, depending on the exact choice of model parameters. In contrast, if the charged portions of the charged side chains are viewed as part of the solvent medium, then theory and simulation are consistent: the protein dipole fluctuations excluding charged side chains are roughly those of a homogeneous, isotropic dielectric medium, with a dielectric constant of 4.7 +/- 1.0 (ferro) or 3.4 +/- 1.0 (ferri), in agreement with powder experiments. Statistical uncertainty and sensitivity to model parameters are small. Analysis of the radial dependence of the dipole fluctuations suggests that the inner half of the protein has a somewhat lower dielectric constant of 1.5-2, consistent with its biological function in electron transfer. These results suggest that Poisson-Boltzmann models could treat the protein bulk as a low-dielectric medium and the charged surface groups as part of the solvent region. PMID- 7862639 TI - Cooperative action of cellular proteins YB-1 and Pur alpha with the tumor antigen of the human JC polyomavirus determines their interaction with the viral lytic control element. AB - Human JC polyomavirus (JCV) is the etiologic agent of the neurodegenerative disease progressive mulifocal leukoencephalopathy. By using JCV as a model, we investigated the role of the viral early protein tumor antigen (TAg) in the binding of two cellular proteins, Pura alpha and YB-1, to JCV regulatory sequences. Results from band-shift assays with purified YB-1, Pur alpha, and TAg indicated that efficient binding of Pur alpha, a strong activator of early gene transcription, to a single-stranded target sequence corresponding to the viral lytic control element, is diminished in the presence of the late gene activator YB-1, which recognizes the opposite strand of the Pur alpha binding site. Of particular interest was the ability of Pur alpha and TAg to enhance binding of YB 1 to DNA molecules without being associated with this complex. Binding studies using a mutant peptide encompassing the N terminus of YB-1 indicated that the C terminus of YB-1 is important for its DNA binding activity. The ability of Pur alpha and TAg to increase binding of YB-1 to DNA is independent of the YB-1 C terminus. Similarly, results from band-shift assays using Pur alpha variants indicated that two distinct regions of this protein contribute either to its ability to bind DNA or to its ability to enhance YB-1 DNA binding activity. Based on the interaction of Pur alpha, YB-1, and TAg, and their binding to DNA, a model is proposed for the role of these proteins in transcription of viral early and late genes during the lytic cycle. PMID- 7862640 TI - Cell cycle-dependent regulation of p185neu: a relationship between disruption of this regulation and transformation. AB - Structure and function of p185neu receptor tyrosine kinase were found to be regulated in a cell cycle-dependent manner. In M phase, p185neu is hyperphosphorylated at serine and/or threonine residues. The phosphotyrosine [Tyr(P)] content of p185neu is at its highest level in G0/G1 phase, decreases through S and G2 phases, and reaches its lowest level in M phase. Phospholipase C gamma (PLC-gamma) and GTPase-activating protein (GAP), substrates of p185neu, also have a similar profile of Tyr(P) content during the cell cycle. These results, along with in vitro immune complex kinase assays, suggest that the tyrosine kinase activity of p185neu is least active in M phase. Interestingly, the mutation-activated neu oncogene (neu*)-encoded protein product, p185neu* escaped from cell cycle regulation. Taken together, we demonstrate in this report that the structure and function of p185neu are regulated in a cell cycle dependent manner, yet p185neu* escapes from this regulation and remains active through the cell cycle. Disruption of this cell cycle regulation may define a mechanism for p185neu*-mediated cellular transformation. PMID- 7862641 TI - Determination of absolute amounts of GDP and GTP bound to Ras in mammalian cells: comparison of parental and Ras-overproducing NIH 3T3 fibroblasts. AB - We devised enzyme-based methods to measure fmol amounts of GDP and GTP and applied these methods to measure absolute amounts of Ras-bound GDP and GTP in NIH 3T3 fibroblasts. We found that parental NIH 3T3 cells contained 509 and 1.3 fmol of Ras-bound GDP and GTP, respectively, per mg of cellular protein and that stable transfectants of NIH 3T3 cells overexpressing wild-type Ha-Ras contained 7008 and 21.3 fmol of Ras-bound GDP and GTP, respectively, per mg of cellular protein; thus, in both cell types < 0.3% of Ras was in the active GTP-bound state. In contrast, NIH 3T3 cells overexpressing an activated form of Ha-Ras contained 5013 and 2049 fmol of Ras-bound GDP and GTP, respectively, per mg of protein, yielding 29% of Ras in the GTP-bound state. Since intracellular Ras is probably all in a guanine-nucleotide bound state, this method allows one to calculate the number of Ras molecules in each cell: parental NIH 3T3 cells and the Ha-Ras overproducing cells contain approximately 20,000 and approximately 275,000 Ras molecules per cell, respectively. We also incubated parental NIH 3T3 cells with 32PO4 and determined the radioactivity in Ras-bound GDP and GTP and the specific activity of cytosolic GDP and GTP; these experiments indicated that Ras-bound GTP may not be in equilibrium with the total cytosolic GTP pool. PMID- 7862642 TI - Identification of presumed ancestral DNA sequences of phaseolin in Phaseolus vulgaris. AB - Common bean (Phaseolus vulgaris) consists of two major geographic gene pools, one distributed in Mexico, Central America, and Colombia and the other in the southern Andes (southern Peru, Bolivia, and Argentina). Amplification and sequencing of members of the multigene family coding for phaseolin, the major seed storage protein of the common bean, provide evidence for accumulation of tandem direct repeats in both introns and exons during evolution of the multigene family in this species. The presumed ancestral phaseolin sequences, without tandem repeats, were found in recently discovered but nearly extinct wild common bean populations of Ecuador and northern Peru that are intermediate between the two major gene pools of the species based on geographical and molecular arguments. Our results illustrate the usefulness of tandem direct repeats in establishing the polarity of DNA sequence divergence and therefore in proposing phylogenies. PMID- 7862643 TI - Sexual dimorphism in the architecture of the lung's gas-exchange region. AB - The lung's only vital function is to provide sufficient gas-exchange surface area (Sa) to meet the organism's needs for oxygen uptake (VO2) and carbon dioxide elimination. A direct linear relation between Sa and VO2 and an inverse linear relation between the size of the lung's gas-exchange units and the species mass specific VO2 are strongly conserved across species. Within species, Sa increases in response to prolonged (weeks) elevation of VO2. We now report sex-dependent deviations from these relationships that seem to anticipate the need for increased gas-exchange capacity engendered in females by the metabolic demands of pregnancy and lactation. We found that although VO2 almost doubled in rats during pregnancy and lactation, Sa was the same in age-matched virgin, pregnant, and lactating females. However, at the onset of sexual maturity, virgin female rats and mice had higher mass-specific Sa than males of the same species although mass specific VO2 was identical, within species, in both sexes. In addition, even though mass-specific VO2 was identical in males and females, alveoli were 30% and 50% smaller in female rats and mice, respectively, than males of the same species. We suggest the greater mass-specific Sa and smaller alveoli in females in spite of identical mass-specific VO2 as males were selected for evolutionarily; they help females meet the metabolic demands of reproduction without adding to the energy demands of these periods a requirement to form additional lung. PMID- 7862644 TI - Directed hydroxyl radical probing of 16S rRNA using Fe(II) tethered to ribosomal protein S4. AB - Localized hydroxyl radical probing has been used to explore the rRNA neighborhood around a unique position in the structure of the Escherichia coli 30S ribosomal subunit. Fe(II) was attached to ribosomal protein S4 at Cys-31 via the reagent 1 (p-bromoacetamidobenzyl)-EDTA. [Fe-Cys31]S4 was then complexed with 16S rRNA or incorporated into active 30S ribosomal subunits by in vitro reconstitution with 16S rRNA and a mixture of the remaining 30S subunit proteins. Hydroxyl radicals generated from the tethered Fe resulted in cleavage of the 16S rRNA chain in two localized regions of its 5' domain. One region spans positions 419-432 and is close to the multihelix junction previously placed at the RNA binding site of S4 by chemical and enzymatic protection (footprinting) and crosslinking studies. A second site of directed cleavage includes nucleotides 297-303, which overlap a site that is protected from chemical modification by protein S16, a near neighbor of S4 in the ribosome. These results provide useful information about the three dimensional organization of 16S rRNA and indicate that these two regions of its 5' domain are in close spatial proximity to Cys-31 of protein S4. PMID- 7862645 TI - Stringent control and growth-rate-dependent control have nonidentical promoter sequence requirements. AB - Escherichia coli uses at least two regulatory systems, stringent control and growth-rate-dependent control, to adjust rRNA output to amino acid availability and the steady-state growth rate, respectively. We examined transcription from rrnB P1 promoters containing or lacking the cis-acting UP element and FIS protein binding sites after amino acid starvation. The "core promoter" responds to amino acid starvation like the full-length wild-type promoter; thus, neither the UP element nor FIS plays a role in stringent control. To clarify the relationship between growth-rate-dependent regulation and stringent control, we measured transcription from growth-rate-independent promoters during amino acid starvation. Four rrnB P1 mutants defective for growth-rate control and two other growth-rate-independent promoters (rrnB P2 and pS10) still displayed stringent regulation. Thus, the two systems have different promoter determinants, consistent with the idea that they function by different mechanisms. Two mutations disrupted stringent control of rrnB P1: (i) a multiple base change in the "discriminator" region between the -10 hexamer and the transcription start site and (ii) a double substitution making the promoter resemble the E sigma 70 consensus promoter. These results have important implications for the mechanisms of both stringent control and growth-rate-dependent control of rRNA transcription. PMID- 7862646 TI - Structural hierarchy in the clustering of HLA class I molecules in the plasma membrane of human lymphoblastoid cells. AB - Major histocompatibility complex (MHC) class I antigens in the plasma membranes of human T (HUT-102B2) and B (JY) lymphoma cells were probed by immunochemical reagents using fluorescence, transmission electron, and scanning force microscopies. Fluorescent labels were attached to monoclonal antibodies W6/32 or KE-2 directed against the heavy chain of HLA class I (A, B, C) and L368 or HB28 against the beta 2-microglobulin light chain. The topological distribution in the nanometer range was studied by photobleaching fluorescence resonance energy transfer (pbFRET) on single cells. A nonrandom codistribution pattern of MHC class I molecules was observed over distances of 2-10 nm. A second, nonrandom, and larger-scale topological organization of the MHC class I antigens was detected by indirect immunogold labeling and imaging by transmission electron microscopy (TEM) and scanning force microscopy (SFM). Although some differences in antigen distribution between the B- and T-cell lines were detected by pbFRET, both cell lines exhibited similar clustering patterns by TEM and SFM. Such defined molecular distributions on the surfaces of cells of the immune system may reflect an underlying specialization of membrane lipid domains and fulfill important functional roles in cell-cell contacts and signal transduction. PMID- 7862647 TI - Quinoxalines block the mechanism of directional selectivity in ganglion cells of the rabbit retina. AB - Direction selectivity is a receptive field property displayed by neurons throughout the visual system. Previous experiments have concentrated on the role of lateral connections that use gamma-aminobutyric acid and acetylcholine. We have examined the role of excitatory amino acid receptors on direction-selective ganglion cell function in the rabbit retina. Application of the quinoxalines, a group of kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonists, selectively blocked the directional-selectivity mechanism, leaving cells responsive to both directions of movement. In contrast, direction selectivity was unaffected by N-methyl-D-aspartate receptor antagonists or L-2 amino-4-phosphonobutyric acid. Large reductions in acetylcholine release by starburst amacrine cells appear to parallel losses of direction selectivity observed in the quinoxalines. These results shed additional insights into the mechanism of direction selectivity. PMID- 7862648 TI - Immunotoxin-mediated conditional disruption of specific neurons in transgenic mice. AB - We have developed a transgenic approach, termed immunotoxin-mediated cell targeting (IMCT), to ablate conditionally selective neurons in the brain with the cytotoxic activity of immunotoxins. Transgenic mice were created that express the human interleukin 2 receptor alpha subunit (IL-2R alpha) under the control of the dopamine beta-hydroxylase (DBH) gene promoter. The animals were treated intracerebroventricularly with a recombinant immunotoxin, anti-Tac(Fv)-PE40, which selectively kills animal cells bearing human IL-2R alpha. The immunotoxin caused a characteristic behavioral abnormality only in the transgenic mice. This was accompanied by a dramatic loss of DBH-containing neurons and a significant decrease in DBH activity and norepinephrine levels in various regions of the brain. IMCT should provide a general technique to create animal models of human neurodegenerative disorders by targeting neurons or other cell types. PMID- 7862649 TI - Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy. AB - Heart failure continues to be a leading cause of mortality worldwide. A hallmark of this disease is dilated cardiac hypertrophy, which is accompanied by a reactivation of genes expressed in fetal heart development. Reasoning that fetal or embryonic growth factors may mediate the onset of cardiac hypertrophy, we have coupled expression cloning with an embryonic stem cell-based model of cardiogenesis to isolate a 21.5-kDa protein, cardiotrophin 1, that potently induces cardiac myocyte hypertrophy in vitro. Amino acid similarity data indicate that cardiotrophin 1 is a member of the leukemia inhibitory factor/ciliary neurotrophic factor/oncostatin M/interleukin 6/interleukin 11 family of cytokines. Several members of this family that are known to signal through the transmembrane protein gp130 stimulate cardiac myocyte hypertrophy, like cardiotrophin 1, suggesting that the gp130 signaling pathway may play a role in cardiac hypertrophy. A 1.4-kb cardiotrophin 1 mRNA is expressed in the heart and several other mouse tissues. PMID- 7862650 TI - Development and characterization of essential fatty acid deficiency in human endothelial cells in culture. AB - We induced an essential fatty acid deficiency (EFAD) in human umbilical vein endothelial cells by culture in medium with 20% (vol/vol) delipidated fetal calf serum. EFAD, reflected by decreased cellular linoleic acid (18:2 omega 6) and arachidonic acid (20:4 omega 6) and emergence of the oleic acid derivative 5,8,11 eicosatrienoic acid (20:3 omega 9; Mead's acid), was evident after 1 week of culture and became pronounced after 2 weeks. Beyond that time point, control cells (cultured in 20% normal fetal calf serum) grew deficient of 18:2 omega 6, and EFAD cells died. 18:2 omega 6 addition to EFAD cells resulted in dose dependent increases of 18:2 omega 6 and 20:4 omega 6. 20:4 omega 6 or 5,8,11,14,17-eicosapentaenoic acid (20:5 omega 3) additions resulted in normalization of these acids, and conversion of 20:5 omega 3 to 4,7,10,13,16,19 docosahexaenoic acid (22:6 omega 3) was noted. Agonist-induced increases in concentrations of prostacycline (prostaglandin I2; PGI2) and cytosolic Ca2+, [Ca2+]i, were reduced in EFAD cells and not restored by 18:2 omega 6 or 20:4 omega 6 additions. Change of the medium in EFAD cultures 1 day before the experiments decreased 20:3 omega 9 and normalized the PGI2 production and [Ca2+]i changes, whereas addition of 20:3 omega 9 to control cells impaired the [Ca2+]i response, indicating a suppressive effect of 20:3 omega 9. Thus, EFAD in endothelial cells is associated with abnormalities of eicosanoid and second messenger production partly attributable to 20:3 omega 9 accumulation. Moreover, the gradual emergence of 18:2 omega 6 deficiency in regularly grown control cells underlines the need for careful analysis of fatty acids in long-term cell cultures. PMID- 7862651 TI - Hypermutability of mouse chromosome 2 during the development of x-ray-induced murine myeloid leukemia. AB - In an effort to identify the precise role of a deletion at regions D-E of mouse chromosome 2 [del2(D-E)] during the development of radiation-induced myeloid leukemia, we conducted a serial sacrifice study in which metaphase chromosomes were examined by the G-banding technique. Such metaphase cells were collected from x-irradiated mice during the period of transformation of some of the normal hematopoietic cells to the fully developed leukemic phenotype. A group of 250 CBA/Ca male mice (10-12 weeks old) were exposed to a single dose of 2 Gy of 250 kilovolt-peak x-rays; 42 age-matched male mice served as controls. Groups of randomly selected mice were sacrificed at 20 hr, 1 week, and then at intervals of 3 months up to 24 months after x-irradiation. Slides for cytogenetic, hematological, and histological examination were prepared for each animal at each sacrifice time. An expansion of cells with lesions on one copy of chromosome 2 was evident in 20-25% of treated mice at each sacrifice time. The majority of such lesions were translocations at 2F or 2H, strongly suggesting hypermutability of these sites on mouse chromosome 2. No lesions were found in control mice. The finding leads to the possibility that genomic lesions close to 2D and 2E are aberrants associated with radiation leukemogenesis, whereas a single clone of cells with a del2(D-E) may lead directly to overt leukemia. The data also indicate that leukemic transformation arises from the cumulative effects of multiple genetic events on chromosome 2, reinforcing the thesis that multiple steps of mutation occur in the pathogenesis of cancer. PMID- 7862652 TI - Modulation of protein tyrosine phosphorylation in rat insular cortex after conditioned taste aversion training. AB - Protein tyrosine phosphorylation is a major signal transduction pathway involved in cellular metabolism, growth, and differentiation. Recent data indicate that tyrosine phosphorylation also plays a role in neuronal plasticity. We are using conditioned taste aversion, a fast and robust associative learning paradigm subserved among other brain areas by the insular cortex, to investigate molecular correlates of learning and memory in the rat cortex. In conditioned taste aversion, rats learn to associate a novel taste (e.g., saccharin) with delayed poisoning (e.g., by LiCl injection). Here we report that after conditioned taste aversion training, there is a rapid and marked increase in tyrosine phosphorylation of a set of proteins in the insular cortex but not in other brain areas. A major protein so modulated, of 180 kDa, is abundant in a membrane fraction and remains modulated for more than an hour after training. Exposure of the rats to the novel taste alone results in only a small modulation of the aforementioned proteins whereas administration of the malaise-inducing agent per se has no effect. To the best of our knowledge, this is the first demonstration of modulation of protein tyrosine phosphorylation in the brain after a behavioral experience. PMID- 7862653 TI - Retrovirus-mediated transfer of an angiotensin type I receptor (AT1-R) antisense sequence decreases AT1-Rs and angiotensin II action in astroglial and neuronal cells in primary cultures from the brain. AB - The AT1-R has been implicated in many cellular and physiological actions of angiotensin II (AII) in the brain. A retrovirus vector (LNSV) containing an AT1B R antisense sequence (AT1B-AS) (termed LNSV-AT1B-AS) was constructed and used to determine the feasibility of using viral-mediated gene transfer to control AT1-Rs and AII actions in astroglial and neuronal cells in primary cultures from rat brain. Briefly, a 1.26-kb antisense sequence corresponding to nt -132 to +1128 of AT1-R cDNA was cloned into the LNSV vector, the vector was transfected into PA317 cells, and transfected cells were selected in G418. Incubation of brain cells with culture medium containing LNSV-AT1B-AS viral particles showed that AT1B-AS was integrated into the genome and transcribed in brain cells. This was associated with a significant decrease in AT1-Rs and in the AII-stimulated increase of c-fos mRNA, a measure of AT1-R function. These observations show that the AT1B-AS gene can be transferred into astroglial cells in culture by LNSV and that such a transfer inhibits AT1-Rs and the AII stimulation of cellular activities. In addition, the usefulness of this approach to study AII-dependent pathophysiology in primary neuronal cultures from brain, in particular, is established. PMID- 7862654 TI - Targeting the maize T-urf13 product into tobacco mitochondria confers methomyl sensitivity to mitochondrial respiration. AB - The URF13 protein, which is encoded by the maize mitochondrial T-urf13 gene, is thought to be responsible for pathotoxin and methomyl sensitivity and male sterility. We have investigated whether T-urf13 confers toxin sensitivity and male sterility when expressed in another plant species. The coding sequence of T urf13 was fused to a mitochondrial targeting presequence, placed under the control of the cauliflower mosaic virus 35S promoter, and introduced into tobacco by Agrobacterium tumefaciens-mediated transformation. Plants expressing high levels of URF13 were methomyl sensitive. Subcellular analysis indicated that URF13 is mainly associated with the mitochondria. Adding methomyl to isolated mitochondria stimulated NADH-linked respiration and uncoupled oxidative phosphorylation, indicating that URF13 was imported into the mitochondria, and conferred toxin sensitivity. Most control plants, which expressed the T-urf13c construct lacking the mitochondrial presequence, were methomyl sensitive and contained URF13 in a membrane fraction. Subcellular fractionation by sucrose gradient centrifugation showed that URF13 sedimented at several positions, suggesting the protein is associated with various organelles, including mitochondria. No methomyl effect was observed in isolated mitochondria, however, indicating that URF13 was not imported and did not confer toxin sensitivity to the mitochondria. Thus, URF13 confers toxin sensitivity to transgenic tobacco with or without import into the mitochondria. There was no correlation between the expression of URF13 and male sterility, suggesting either that URF13 does not cause male sterility in transgenic tobacco or that URF13 is not expressed in sufficient amounts in the appropriate anther cells. PMID- 7862655 TI - A common fold for peptide synthetases cleaving ATP to ADP: glutathione synthetase and D-alanine:d-alanine ligase of Escherichia coli. AB - Examination of x-ray crystallographic structures shows the tertiary structure of D-alanine:D-alanine ligase (EC 6.3.2.4). a bacterial cell wall synthesizing enzyme, is similar to that of glutathione synthetase (EC 6.32.3) despite low sequence homology. Both Escherichia coli enzymes, which convert ATP to ADP during ligation to produce peptide products, are made of three domains, each folded around a 4-to 6-stranded beta-sheet core. Sandwiched between the beta-sheets of the C-terminal and central domains of each enzyme is a nonclassical ATP-binding site that contains a common set of spatially equivalent amino acids. In each enzyme, two loops are proposed to exhibit a required flexibility that allows entry of ATP and substrates, provides protection of the acylphosphate intermediate and tetrahedral adduct from hydrolysis during catalysis, and then permits release of products. PMID- 7862656 TI - Induction of heme oxygenase 1 in the retina by intense visible light: suppression by the antioxidant dimethylthiourea. AB - The effect of intense visible light (light damage) on the expression of heme oxygenase 1 (HO-1), a protein induced by oxidative stress, was investigated in the rat retina. A sensitive reverse transcription-PCR assay demonstrated the expression of mRNA for HO-1 as well as HO-2, the noninducible HO form, in the normal retina. As analyzed by Northern blotting, however, HO-1 mRNA was barely detectable under normal circumstances. After exposure to intense visible light, retinas had markedly higher HO-1 mRNA levels than unexposed controls, with increases up to 52- and 98-fold at 12 and 24 hr of exposure, respectively. Intense light exposure also resulted in an increase in HO-1 protein. In contrast, no appreciable change in HO-2 mRNA or protein was observed. The increase in HO-1 message was more pronounced in rats previously reared in the dark than in those reared in a weak cyclic-light environment. A marked decrease from the high level of HO-1 mRNA induced by light insult was observed when the animals were allowed to recover in the dark for 24 hr after light exposure. Most important, treatment of animals with 1,3-dimethylthiourea, a synthetic antioxidant, prior to light exposure effectively blocked the increase in HO-1 mRNA. Thus, HO-1 is a sensitive marker for assessing light-induced insult in the retina. Since increased expression of HO-1 is thought to be a cellular defense against oxidative damage, its expression may play an important role in protecting the retina against light damage. PMID- 7862657 TI - G1 cyclin-dependent activation of p34CDC28 (Cdc28p) in vitro. AB - In Saccharomyces cerevisiae, transient accumulation of G1 cyclin/p34CDC28 (Cdc28p) complexes induces cells to traverse the cell cycle Start checkpoint and commit to a round of cell division. To investigate posttranslational controls that modulate Cdc28p activity during the G1 phase, we have reconstituted cyclin dependent activation of Cdc28p in a cyclin-depleted G1 extract. A glutathione S transferase-G1 cyclin chimera (GST-Cln2p) efficiently binds to and activates Cdc28p as a histone H1 kinase. Activation of Cdc28p by GST-Cln2p requires ATP, crude yeast cytosol, and the conserved Thr-169 residue that serves in other organisms as a substrate for phosphorylation by cyclin-dependent protein kinase activating kinase. This assay may be useful for distinguishing genes that promote directly the posttranslational assembly of active Cln2p/Cdc28p kinase complexes from those that stimulate the accumulation of active complexes via a positive feedback loop that governs synthesis of G1 cyclins. PMID- 7862658 TI - Disruption of the nucleoporin gene NUP133 results in clustering of nuclear pore complexes. AB - We have characterized a protein with an estimated molecular mass of 130 kDa that is contained in a highly enriched yeast nuclear pore complex (NPC) fraction. Partial amino acid sequence from this protein has led us to a previously identified open reading frame on chromosome XI of Saccharomyces cerevisiae encoding a protein of 133 kDa. Due to its coenrichment with NPCs during cell fractionation and the phenotype observed in the disrupted strain, we propose to term the gene encoding this protein NUP133. Cells carrying a disrupted copy of NUP133 were temperature sensitive for growth. In addition, abnormal clustering of NPCs was observed. This phenotype is similar to that previously observed in the disruption of another nucleoporin gene, NUP145. We speculate that the gene product of NUP133, Nup133p, may functionally overlap with the NUP145 gene product, Nup145p, and that these proteins may be involved in maintaining the position of the NPC within the nuclear envelope. PMID- 7862659 TI - Paternal investment affects prevalence of malaria. AB - Both reproduction and parasite defense can be costly, and an animal may face a trade-off between investing in offspring or in parasite defense. In contrast to the findings from nonexperimental studies that the poorly reproducing individuals are often the ones with high parasite loads, this life-history view predicts that individuals with high reproductive investment will show high parasite prevalence. Here we provide an experimental confirmation of a positive association between parental investment levels of male great tits Parus major and the prevalence of Plasmodium spp, a hematozoa causing malaria in various bird species. We manipulated brood size, measured feeding effort of both males and females, and assessed the prevalence of the hemoparasite from blood smears. In enlarged broods the males, but not the females, showed significantly higher rates of food provisioning to the chicks, and the rate of malarial infection was found to be more than double in male, but not female, parents of enlarged broods. The findings show that there may be a trade-off between reproductive effort and parasite defense of the host and also suggest a mechanism for the well documented trade-off between current reproductive effort and parental survival. PMID- 7862660 TI - Passive immunotherapy in AIDS: a double-blind randomized study based on transfusions of plasma rich in anti-human immunodeficiency virus 1 antibodies vs. transfusions of seronegative plasma. AB - A randomized double-blind controlled trial was conducted to determine the efficacy of passive immunotherapy in the treatment of symptomatic human immunodeficiency virus (HIV) infection. This trial included 86 symptomatic patients randomized to receive plasma rich in anti-HIV-1 antibody or standard seronegative plasma. Each patient in both groups received a 300-ml infusion every 14 days over a 1-year period, and every 28 days thereafter, in addition to zidovudine and other conventional prophylactic treatments. Plasma donors were selected among symptomless seropositive individuals with a CD4 lymphocyte count > or = 400 x 10(6) cells per liter, a negative p24 antigen assay, and a high concentration of anti-p24 antibody. The plasmas were heat-inactivated before infusion. During the study period (day 28-day 365) scheduled by the protocol, clinical benefit from passive immunotherapy was observed in delaying the appearance of the first AIDS-defining event (P < 0.009) and reducing the cumulative incidence of such events, which was estimated 3-fold higher in the control group compared to the treatment group. Seven deaths occurred in the treatment group vs. 11 in the control group (P = 0.27). A total of 47 patients died or exhibited new AIDS-defining events, 18 in the treatment group and 29 in the control group (P = 0.009). No clinical benefit was observed after the 1-year period with infusions performed every 4 weeks. These results indicate a favorable effect of passive immunotherapy on the evolution of advanced AIDS. PMID- 7862661 TI - Positive selection of invariant V alpha 14+ T cells by non-major histocompatibility complex-encoded class I-like molecules expressed on bone marrow-derived cells. AB - V alpha 14+ T cells are a unique subset expressing an invariant T-cell antigen receptor alpha chain encoded by V alpha 14 and J alpha 281 gene fragments with a 1-nt N region. Most invariant V alpha 14+ T cells develop in extrathymic organs, independent of thymus, and expand at a high frequency in various mouse strains regardless of major histocompatibility complex (MHC) haplotype. In this paper, we show that the positive selection of invariant V alpha 14+ T cells requires a beta 2-microglobulin-associated MHC class I-like molecule not linked to the MHC on chromosome 17. This was determined by linkage analysis on DNA from recombinant mice generated by crossing a C57BL/6 mouse with a wild mouse, Mus musculus molossinus, that is negative for invariant V alpha 14 TCR expression. However, the peptide transporter TAP1 is not necessary for positive selection of invariant V alpha 14+ T cells, indicating the direct recognition of the MHC class I-like molecule without peptide by the invariant V alpha 14 TCR. Further, experiments with bone marrow-chimeric mice show that invariant V alpha 14+ T cells in the periphery are selected by bone marrow cells, suggesting a unique lineage of V alpha 14+ T cells differentiated through a selection process distinct from that of conventional alpha beta TCR+ T cells. PMID- 7862662 TI - Hydrogen bonding in water using synthetic receptors. AB - Four water-soluble adenine receptors were synthesized to study the influence of hydrophobic interactions and hydrogen bonding on molecular recognition in aqueous solution. Association constants were measured in aqueous solution at five temperatures from 3-27 degrees C (pH 6, 51 mM ionic strength). For the mono(imide) receptors, delta H was -5.8 kcal/mol (carbazole) and -9.2 kcal/mol (naphthalene). The entropy of association for these was -13 cal.mol-1.K-1 (carbazole) and -26 cal.mol-1.K-1 (naphthalene). The carbazole bis(imide) receptor showed a binding enthalpy of -7.4 kcal/mol and entropy of -18 cal.mol 1.K-1. From this the free energy at 298 K of a single hydrogen bond is estimated to be only 0.2 kcal/mol. The enthalpy of a single hydrogen bond in this solvent exposed system is estimated to be, at most, 0.8 kcal/mol, indicating that enthalpy just compensates for the unfavorable entropy in this system. These values reflect stronger hydrophobic interactions with the more polarizable naphthalene, as well as enthalpy-entropy compensation effects. PMID- 7862663 TI - Identification of galectin-3 as a factor in pre-mRNA splicing. AB - Galectin-3 (M(r) approximately 35,000) is a galactose/lactose-specific lectin found in association with ribonucleoprotein complexes in many animal cells. Cell free-splicing assays have been carried out to study the requirement for galectin 3 in RNA processing by HeLa cell nuclear extracts by using 32P-labeled MINX as the pre-mRNA substrate. Addition of saccharides that bind galectin-3 with high affinity inhibited product formation in the splicing assay, while addition of carbohydrates that do not bind to the lectin did not inhibit product formation. Nuclear extracts depleted of galectin-3 by affinity adsorption on a lactose agarose column were deficient in splicing activity. Extracts subjected to parallel adsorption on control cellobiose-agarose retained splicing activity. The activity of the galectin-3-depleted extract could be reconstituted by the addition of purified recombinant galectin-3, whereas the addition of other lectins, either with a similar saccharide binding specificity (soybean agglutinin) or with a different specificity (wheat germ agglutinin), did not restore splicing activity. The formation of splicing complexes was also sensitive to galectin-3 depletion and reconstitution. Together, these results define a requirement for galectin-3 in pre-mRNA splicing and identify it as a splicing factor. PMID- 7862664 TI - The three-dimensional structure of a class I major histocompatibility complex molecule missing the alpha 3 domain of the heavy chain. AB - Class I major histocompatibility complex (MHC) molecules are ternary complexes of the soluble serum protein beta 2-microglobulin, MHC heavy chain, and bound peptide. The first two domains (alpha 1, alpha 2) of the heavy chain create the peptide binding cleft and the surface that contacts the T-cell receptor. The third domain (alpha 3) associates with the T-cell co-receptor, CD8, during T-cell recognition. Here we describe the x-ray crystal structure of a human class I MHC molecule, HLA-Aw68, from which the alpha 3 domain has been proteolytically removed. The resulting molecule shows no gross morphological changes compared to the intact protein. A decameric peptide complexed with the intact HLA-Aw68 is seen to bind to the proteolized molecule in the conventional manner, demonstrating that the alpha 3 domain is not required for the structural integrity of the molecule or for peptide binding. PMID- 7862665 TI - Contribution of cotranslational folding to the rate of formation of native protein structure. AB - To compare the process of protein folding in the cell with refolding following denaturation in vitro, we have investigated and compared the kinetics of renaturation of a full-length protein upon dilution from concentrated urea with the rate of folding in the course of biosynthesis. Formation of enzymatically active bacterial luciferase, an alpha beta heterodimer, occurred 2 min after completion of beta-subunit synthesis in an Escherichia coli cell-free system. Renaturation of urea-denatured beta subunit, either in the presence of the cell free protein synthesis system or in buffer solutions, proceeded more slowly. Cellular components present in the cell-free protein synthesis system slightly accelerated the rate of refolding of urea-unfolded beta subunit. The results indicate that the luciferase beta subunit begins the folding process cotranslationally and that cotranslational folding contributes to the rapid formation of the native structure in the cell. PMID- 7862666 TI - Amino acid sequence of rat kidney glutathione synthetase. AB - Glutathione (GSH) synthetase [gamma-L-glutamyl-L-cysteine:glycine ligase (ADP forming), EC 6.3.2.3], an enzyme present in almost all cells, catalyzes the ATP dependent synthesis of GSH from gamma-L-glutamyl-L-cysteine and glycine. Highly purified preparations of the enzyme have been obtained from rat kidney and several lower forms. The rat kidney enzyme (M(r), 118,000), which contains approximately 2% carbohydrate, is composed of two apparently identical subunits. The cDNA encoding rat kidney GSH synthetase was isolated from a rat kidney lambda gt11 cDNA library by immunoscreening with an antibody prepared against the isolated enzyme. The cDNA contains 1905 nucleotides and an open reading frame of 1422 nucleotides coding for 474 amino acids. The cDNA has a 3' untranslated region of 439 nucleotides, which includes a poly(A) tail. The deduced amino acid sequence (M(r), 52,344) contains all five of the peptide sequences that were independently determined by Edman degradation. The cDNA was expressed in Escherichia coli. The amino acid sequence of the rat kidney enzyme has no significant similarity to that of the enzyme from E. coli and shows some similarity to those deduced for the yeast and frog enzymes. Knowledge of this amino acid sequence is expected to facilitate elucidation of the sequence of the corresponding human enzyme and to lead to studies on the biochemical mechanisms involved in human GSH synthetase deficiency as well as to development of improved methods for prenatal diagnosis of these inborn diseases. PMID- 7862667 TI - Conservation of deposition-related acetylation sites in newly synthesized histones H3 and H4. AB - Newly synthesized histone H4 is deposited in a diacetylated isoform in a wide variety of organisms. In Tetrahymena a specific pair of residues, lysines 4 and 11, have been shown to undergo this modification in vivo. In this report, we demonstrate that the analogous residues, lysines 5 and 12, are acetylated in Drosophila and HeLa H4. These data strongly suggest that deposition-related acetylation sites in H4 have been highly, perhaps absolutely, conserved. In Tetrahymena and Drosophila newly synthesized histone H3 is also deposited in several modified forms. Using pulse-labeled H3 we have determined that, like H4, a specific, but distinct, subset of lysines is acetylated in these organisms. In Tetrahymena, lysines 9 and 14 are highly preferred sites of acetylation in new H3 while in Drosophila, lysines 14 and 23 are strongly preferred. No evidence has been obtained for acetylation of newly synthesized H3 in HeLa cells. Thus, although the pattern and sites of deposition-related acetylation appear to be highly conserved in H4, the same does not appear to be the case for histone H3. PMID- 7862668 TI - Independent regulation of sterol regulatory element-binding proteins 1 and 2 in hamster liver. AB - Two sterol regulatory element-binding proteins (SREBPs, designated SREBP-1 and SREBP-2), each approximately 1150 amino acids in length, are attached to membranes of the endoplasmic reticulum and nuclear envelope in human and hamster tissue culture cells. In the absence of sterols, soluble fragments of approximately 470 amino acids are released from both proteins by proteolytic cleavage. The soluble fragments enter the nucleus, where they bind to sterol regulatory elements in the promoters of genes encoding the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl CoA synthase, thereby activating transcription. Proteolytic processing of both SREBPs is blocked coordinately by sterol overloading and enhanced coordinately when sterols are depleted by treatment with an inhibitor of cholesterol synthesis. In contrast to these findings in cultured cells, the current data show that SREBP-1 and -2 are not coordinately regulated in hamster liver. In untreated animals the soluble fragment of SREBP-1, but not of SREBP-2, was detected by immunoblotting of a liver nuclear extract. Depletion of sterols by treatment with a bile acid-binding resin (colestipol) and a cholesterol synthesis inhibitor (mevinolin) led to a marked increase in the nuclear form of SREBP-2 and a reciprocal decline in the nuclear form of SREBP-1. These findings suggest that SREBP-1 is responsible for basal transcription of the low density lipoprotein receptor and 3-hydroxy-3 methylglutaryl CoA synthase genes in hamster liver and that SREBP-2 is responsible for the increased transcription that follows sterol depletion with a bile acid-binding resin and a cholesterol synthesis inhibitor. PMID- 7862669 TI - cDNA cloning of prophenoloxidase from the freshwater crayfish Pacifastacus leniusculus and its activation. AB - Prophenoloxidase (proPO), an enzyme that is the terminal component of the so called proPO activating system, a defense and recognition system in crustaceans and insects, has been purified and cloned from a crayfish blood cell cDNA library. The deduced amino acid sequence codes for a polypeptide with a mass of 80,732 Da, which is close to 76 kDa, the apparent mass of the purified enzyme. proPO contains two copper atoms, and two putative copper-binding sites were found in the deduced amino acid sequence. Sequence comparisons show that these putative copper-binding sites are similar to the corresponding sites in arthropod hemocyanins and also, although the sequence similarities are less extensive, similar to tyrosinases from vertebrates and microorganisms. The purified enzyme is a typical tyrosinase because it hydroxylates monophenols and oxidizes o diphenols but does not oxidize p-diphenols. If a homogeneous preparation of crayfish proPO were incubated with a homogeneous sample of the proPO activating enzyme, a serine proteinase, the cleavage of proPO by this trypsin-like enzyme was found to occur between Arg-176 and Thr-177. PMID- 7862670 TI - MARCKS deficiency in mice leads to abnormal brain development and perinatal death. AB - The MARCKS protein is a widely distributed cellular substrate for protein kinase C. It is a myristoylprotein that binds calmodulin and actin in a manner reversible by protein kinase C-dependent phosphorylation. It is also highly expressed in nervous tissue, particularly during development. To evaluate a possible developmental role for MARCKS, we disrupted its gene in mice by using the techniques of homologous recombination. Pups homozygous for the disrupted allele lacked detectable MARCKS mRNA and protein. All MARCKS-deficient pups died before or within a few hours of birth. Twenty-five percent had exencephaly and 19% had omphalocele (normal frequencies, < 1%), indicating high frequencies of midline defects, particularly in cranial neurulation. Nonexencephalic MARCKS deficient pups had agenesis of the corpus callosum and other forebrain commissures, as well as failure of fusion of the cerebral hemispheres. All MARCKS deficient pups also displayed characteristic lamination abnormalities of the cortex and retina. These studies suggest that MARCKS plays a vital role in the normal developmental processes of neurulation, hemisphere fusion, forebrain commissure formation, and formation of cortical and retinal laminations. We conclude that MARCKS is necessary for normal mouse brain development and postnatal survival. PMID- 7862671 TI - A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. AB - Thiopurine S-methyltransferase (TPMT; S-adenosyl-L-methionine:thiopurine S methyltransferase, EC 2.1.1.67) activity exhibits genetic polymorphism, with approximately 0.33% of Caucasians and African-Americans inheriting TPMT deficiency as an autosomal recessive trait. To determine the molecular genetic basis for this polymorphism, we cloned the TPMT cDNA from a TPMT-deficient patient who had developed severe hematopoietic toxicity during mercaptopurine therapy. Northern blot analysis of RNA isolated from leukocytes of the deficient patient demonstrated the presence of TPMT mRNAs of comparable size to that in subjects with high TPMT activity. Sequencing of the mutant TPMT cDNA revealed a single point mutation (G238-->C), leading to an amino acid substitution at codon 80 (Ala80-->Pro). When assessed in a yeast heterologous expression system, this mutation led to a 100-fold reduction in TPMT catalytic activity relative to the wild-type cDNA, despite a comparable level of mRNA expression. A mutation specific PCR amplification method was developed and used to detect the G238-->C mutation in genomic DNA of the propositus and her mother. This inactivating mutation in the human TPMT gene provides insights into the genetic basis for this inherited polymorphism in drug metabolism. PMID- 7862672 TI - Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons. AB - Mutation in superoxide dismutase 1 (SOD1), a Cu/Zn enzyme that removes oxygen radicals and protects against oxidative injury, has been implicated in some cases of familial amyotrophic lateral sclerosis (FALS). As a first approach to examining the mechanism(s) through which these mutations cause specific degeneration of motor neurons, we have used immunocytochemistry to identify the distribution of SOD1 in populations of cells in the peripheral and central nervous systems. In the spinal cord, intense SOD1 immunoreactivity was present in motor neurons, interneurons, and substantia gelatinosa. In motor neurons, SOD1 immunoreactivity was abundant in perikarya, dendrites, and axons; most of this activity appeared to be free in the cytoplasm, although a portion was associated with membranous vesicles, presumably peroxisomes. Since a variety of central nervous system neurons, including pyramidal cells in cerebral cortex and neurons of the CA3 and CA4 sectors of the hippocampus, showed high immunoreactivity but are unaffected in ALS, the apparent abundance of SOD1 does not predict vulnerability of neurons to mutations in SOD1. Rather, SOD1 accumulates in many neuronal populations but is particularly abundant in motor neurons. Consistent with recent studies of FALS-linked SOD1 mutations in vitro and in transgenic mice, our findings offer further support for the view that the mutations confer a gain of adverse function. In this view, high, rather than limiting, levels of SOD1 may place motor neurons selectively at risk in FALS. PMID- 7862673 TI - A single arginine residue determines species specificity of the human growth hormone receptor. AB - Although growth hormone (GH) receptors (GHRs) in many species bind human (h) GH as well as their own GH, the hGHR only binds primate GH. Arg43 in hGHR interacts with Asp171 of hGH. Nonprimates have a His in the position equivalent to residue 171 of primate GH and a Leu in position 43 of primate GHR. To determine whether Arg43 accounts for the species specificity of the hGHR, point mutations that changed Leu43 to Arg were introduced into the cDNAs encoding the bovine (b) GHR or the rat GH binding protein (GHBP) and these mutants or their wild-type (WT) counterparts were expressed in mouse L cells. Binding of hGH or bGH to transfected cells or to GHBP secreted into the incubation medium was assessed by displacement of 125I-labeled hGH. WT and mutant bGHR bound hGH with similar affinity, but the affinity of the mutant receptors for bGH was reduced 200-fold. Likewise, WT and mutant GHBP bound hGH with equal affinity, but only WT GHBP bound bGH. Cross-linking of 125I-labeled hGH to WT or mutant GHR produced a 141 kDa labeled complex whose appearance was blocked by unlabeled hGH, but bGH blocked cross-linking only to WT receptors. Both hGH and bGH stimulated tyrosine phosphorylation of a 95-kDa protein in cells transfected with WT GHR, but bGH was less effective in cells expressing mutant GHR. We conclude that incompatibility of Arg43 in the hGHR with His171 in nonprimate GH is the major determinant of species specificity. PMID- 7862674 TI - Maize branching enzyme catalyzes synthesis of glycogen-like polysaccharide in glgB-deficient Escherichia coli. AB - The structure of alpha-glucan, isolated from wild-type Escherichia coli B, a glycogen branching enzyme (BE)-deficient E. coli AC71 (glgB-), or from AC71 transformed with genes coding for maize BEI and BEII individually as well as with both genes, was analyzed by high-performance anion-exchange chromatography (HPAEC) with pulsed amperometric detection. Transformation of the maize BE gene(s) in AC71 (glgB-) showed complementation in branching activity. Analysis by HPAEC revealed different structures between glycogen of E. coli B and alpha glucan of AC71 transformed with a different maize BE gene(s). The individual chains of the alpha-glucan debranched with isoamylase were distributed between chain length (CL) 3 and > 30 and the chain with CL 6 was the most abundant. In comparison with the glycogen of E. coli B, the alpha-glucan of AC71 transformed with the maize BE gene(s) consisted of a lesser amount of chains with CL 7-9 and a larger amount of chains with CL > 14. It also showed a broad peak with chains of CL 9-12 as in maize amylopectin. This study provides in vivo evidence that glycogen BE and maize BE isozymes may have different specificities in the length of chain transferred. Furthermore, this study suggests that the specificity of glycogen synthase and starch synthase and their concerted action with BE play an important role in determining the structure of the polysaccharide synthesized. PMID- 7862675 TI - The minor form alpha' chain from lamprey fibrinogen is rapidly crosslinked during clotting. AB - Lampreys have two genes for the alpha chains of fibrinogen, the second of which encodes a minor form with a carboxyl-terminal domain homologous to the carboxyl terminal domains of beta and gamma chains. Initially, we referred to the alternative chain as alpha-II; we now use the designation alpha' in order to facilitate reference to crosslinked dimers. Antisera raised to synthetic peptides based on the cDNA sequence confirmed that the alpha' chain was present in fibrinogen prepared directly from plasma. The same antibodies were used to determine the size and properties of the carboxyl-terminal domain after its release by mild tryptic digestion, a fragment of apparent molecular weight 35,000 40,000 being produced. Unlike fragment D generated in the same digestions, the alpha' fragment did not bind to Gly-Pro-Arg or Gly-Val-Arg peptide affinity columns. During clotting under conditions where factor XIII is active, the alpha' chains became crosslinked very much more rapidly than ordinary alpha chains, the principal product being an apparent dimer, but smaller amounts of higher multimers being detectable. The crosslinking was inhibited by various amines, as well as by peptides that prevent polymerization. PMID- 7862676 TI - Transfection of Plasmodium falciparum within human red blood cells. AB - Plasmodium falciparum malaria parasites within human red blood cells (RBCs) have been successfully transfected to produce chloramphenicol acetyltransferase (CAT). Electroporation of parasitized RBCs was used to introduce plasmids that have CAT encoding DNA flanked by 5' and 3' untranslated sequences of the P. falciparum hsp86, hrp3, and hrp2 genes. These flanking sequences were required for expression as their excision abolished CAT activity in transfected parasites. Transfection signals from native CAT-encoding DNA compared well with those from a synthetic DNA sequence adapted to the P. falciparum major codon bias, demonstrating effective expression of the bacterial sequence despite its use of rare P. falciparum codons. Transfected ring-stage parasites produced CAT signals at least as strong as transfected schizont-stage parasites even though ring stages are surrounded by more RBC cytoplasm than schizonts. The transfection of erythrocyte-stage P. falciparum parasites advances our ability to pursue genetic analysis of this major pathogen. PMID- 7862677 TI - Adherence of human immunodeficiency virus-infected lymphocytes to fetal placental cells: a model of maternal --> fetal transmission. AB - The precise timing and mechanism of in utero human immunodeficiency virus (HIV) infection are unknown, but transplacental transmission is likely. Term placentas from HIV+ pregnancies contain only rare HIV-infected cells whose origins and phenotypes remain controversial, and no correlation has been found between the presence of HIV in term placentas and transmission to offspring. Reports of trophoblast infectibility have not been reproducible and do not address the question of infection in the placental stroma, the cells in direct contact with fetal circulation. We report that primary cultures of fetal placental chorionic villus stromal cells, while not infectable in vitro, do support lethally irradiated HIV-infected peripheral blood mononuclear cells (PBMCs) in a form that permits rescue of HIV by activated PBMCs weeks later. Infected PBMCs adhere and become intimately associated with placental cells by a mechanism that is LFA-1 and CD4 independent but can be blocked by antibodies or soluble CD4 binding to cell surface-expressed HIV envelope. The ability to sustain infected irradiated cells was not shared by several trophoblast, fibroblast, or epithelial cell lines. This model has several features that are compatible with in utero transmission and allow testing of various agents proposed as interventions to block maternal-->fetal transmission. Placental stromal cells appear to inhibit apoptosis of HIV-infected, irradiated lymphocytes. PMID- 7862678 TI - Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus. AB - Recent studies have demonstrated that reduced insulin-stimulated muscle glycogen synthesis is the major cause of insulin resistance in patients with non-insulin dependent diabetes mellitus (NIDDM). This reduced rate has been assigned to a defect in either glucose transport or hexokinase activity. However it is unknown whether this is a primary or acquired defect in the pathogenesis of NIDDM. To examine this question, we measured the rate of muscle glycogen synthesis and the muscle glucose 6-phosphate (G6P) concentration using 13C and 31P NMR spectroscopy as well as oxidative and nonoxidative glucose metabolism in six lean, normoglycemic offspring of parents with NIDDM and seven age/weight-matched control subjects under hyperglycemic (approximately 11 mM)-hyperinsulinemic (approximately 480 pM) clamp conditions. The offspring of parents with NIDDM had a 50% reduction in total glucose metabolism, primarily due to a decrease in the nonoxidative component. The rate of muscle glycogen synthesis was reduced by 70% (P < 0.005) and muscle G6P concentration was reduced by 40% (P < 0.003), which suggests impaired muscle glucose transport/hexokinase activity. These changes were similar to those previously observed in subjects with fully developed NIDDM. When the control subjects were studied at similar insulin levels (approximately 440 pM) but euglycemic plasma glucose concentration (approximately 5 mM), both the rate of glycogen synthesis and the G6P concentration were reduced to values similar to the offspring of parents with NIDDM. We conclude that insulin resistant offspring of parents with NIDDM have reduced nonoxidative glucose metabolism and muscle glycogen synthesis secondary to a defect in muscle glucose transport/hexokinase activity prior to the onset of overt hyperglycemia. The presence of this defect in these subjects suggests that it may be the primary factor in the pathogenesis of NIDDM. PMID- 7862679 TI - Visual latencies in cytochrome oxidase bands of macaque area V2. AB - Cytochrome oxidase bands in area V2 of the primate visual cortex constitute separate relays for parallel channels relaying information from area V1 to other extrastriate cortical areas. We investigated whether information is transferred at the same speed in the different channels by measuring the latencies of neurons in different cytochrome oxidase bands identified by the presence or absence of retrogradely labeled cells from injections in area V4. Results show that neurons in the thick and pale bands respond 20 msec earlier than those in the thin bands. We also found that color-selective neurons respond later than neurons with no selectivity for color and that direction-selective neurons have shorter latencies than neurons with no selectivity for the direction of stimulus movement. PMID- 7862681 TI - NHS or nhs? PMID- 7862680 TI - A motion area in human visual cortex. AB - We have localized an area in the human brain involved in the processing of contours defined by motion differences (kinetic contours) by comparing with positron emission tomography the regional cerebral blood flow in tasks performed with kinetic and luminance-defined gratings. These tasks included passive viewing, counting the total number of grating stimuli, and counting the number of gratings of a given orientation. Comparison between the counting tasks and passive viewing with a given type of contour revealed a set of active areas that were similar for both luminance-defined and kinetic contours. Comparisons between these two types of contours revealed a single focus in the right hemisphere that did not overlap with the many regions activated by uniform motion. In particular this "kinetic focus" was clearly separated from the area previously defined as the human homologue of V5/middle temporal. Activity in this kinetic focus was stronger when orientation had to be processed than in the other two tasks. These results and control experiments with uniformly moving random dot patterns suggest the existence of an area in the human visual system that is activated much more by kinetic contours than by luminance contours or uniformly moving random dots. Up to now, such an area has not been described in the monkey visual system. PMID- 7862682 TI - Burn wound management: an overview. AB - 1. Accidents resulting in a burn/scald 2. Holistic care for each patient is essential in minimising potential complications in the healing of the burn wound. 3. A family-centred and multidisciplinary approach helps to ensure all physical and psychological needs are met. PMID- 7862683 TI - A means of tying provision with need. Audit of pressure-relieving aids in community-based hospitals. AB - 1. The use of pressure-relieving mattresses should be agreed with the multidisciplinary team according to specific criteria. 2. Criteria led to appropriate mattress being used, with standardised practice based on patients' individual clinical needs. 3. Nurses ensure pressure area care is prescribed, delivered and documented. 4. The audit tools could be amended for use in the community setting and other hospital specialties. PMID- 7862684 TI - A triumphant survival, but at what cost? Meeting the long-term needs of cancer survivors. AB - 1. As more people are treated effectively for cancer, it is important to consider the long-term effects of treatment and the alterations in quality of life. 2. Individual survivors face challenges in coping with physical impairments, psychological adjustments and social discrimination. 3. Rehabilitation programmes need to be devised to help these people make a smooth transition back into the social setting. 4. Financial implications of providing rehabilitation services must be considered. PMID- 7862685 TI - An insight into the afterlife? Informing patients about near death experiences. AB - 1. Patients often feel better able to confide in nurses than doctors on 'difficult' subjects. 2. Research has rejected conventional hallucinatory effects as a conclusive explanation for NDEs. 3. Nurses may legitimately agree that current research at least points to the possibility of continuation of life after death. 4. Research on energy conservation, thermodynamics and behaviour of subatomic particles suggests there is a wavelength of reality beyond the reach of normal sensory perception. PMID- 7862686 TI - A flexible approach yields multiple benefits. Assessment of the benefits of flexible shifts. AB - 1. Analysis of workload pattern is fundamental to human resource management. 2. Patient centred care demands more static staffing levels. 3. Flexibility in working hours enhances staff retention. 4. Reduced pay costs mean ancillary staff can be employed to fulfil non-nursing duties. PMID- 7862687 TI - Autism: is there a biological cause? AB - 1. Autism is the term used to describe certain characteristics observed in some children, including a preference for aloneness, and sameness. 2. The condition was thought for some time to be caused by a psychological disturbance resulting from a combination of stress and poor parental upbringing. 3. Recently emerging data suggests the symptoms are related to a cognitive deficit associated with a biological cause. 4. As research progresses, it is hoped it will become possible to improve the quality of life for people suffering from or looking after those with, autism. PMID- 7862688 TI - Exacerbation of a perennial problem? The theory-practice gap and changes in nurse education. AB - 1. Project 2000, with the introduction of supernumerary status for students, is a major change with the potential to reduce the theory-practice gap. 2. The effect of the mentor and preceptor roles on the theory-practice gap needs to be further evaluated. 3. The moving of nurse education into higher education has many potential benefits, but ongoing evaluation is necessary to ensure the future of nursing is not disadvantaged. 4. A commitment from practitioners, educationalists and managers is needed to reduce the theory-practice gap. PMID- 7862689 TI - Let's treat body and mind. Collaborative rehabilitation for chronic breathlessness. AB - 1. People with emphysema suffer breathlessness and present with varied health and social needs. 2. Needs analysis can usefully use the WHO classification of impairment and handicap, also assisting with the nursing contribution and determining research priorities. 3. Rehabilitation aims to be responsive to clients' needs so they benefit from healthcare. 4. A CPN and RHW discuss their collaborative roles as a whole and finding this of greater value than their individual contributions. PMID- 7862690 TI - A welcome focus on a key relationship. Using Peplau's model in palliative care. AB - 1. Nurses involved in an area of nursing where the nurse-patient relationship is significant would be well advised to review Peplau's work. 2. Peplau sees this relationship as a dynamic one and identifies four phases which interlock and overlap. 3. A significant similarity between the writings of Peplau, Murray Parks and Kubler Ross is the acceptance that the patient/relatives go through a process which has recognisable parts and that nurses can have a significant influence on whether it is a positive or negative experience. PMID- 7862691 TI - Time out for a career break. PMID- 7862692 TI - Modulation of acrylamide-induced neurochemical and behavioral deficits by cerebellar transplants in rats. AB - Acrylamide (30 mg/kg body wt.) administered intraperitoneally daily to young adult male rats, five times a week for 3 consecutive weeks, affected the cerebellar functions, as exhibited by a significant reduction in rotarod performance, spontaneous locomotor activity, glutathione-S-transferase activity, and 3H-flunitrazepam binding in cerebellum. Transplantation of dissociated fetal cerebellar cells (E14) to cerebellum resulted in a significant recovery in behavioral and neurochemical parameters evaluated 9 weeks after transplantation. Light- and electron-microscopic studies confirmed the viability and specificity of cerebellar grafts. PMID- 7862693 TI - Handling alters habituation and response to stimulus change in the holeboard. AB - The responses of rats that had been extensively handled for 18 days were compared in the holeboard with those of rats that had received handling for only 4 days before the test. The extensively handled group showed slower between-day habituation of exploratory head-dipping. They did not differ in the number of head-dips, but spent longer head-dipping, at holes with objects than at those without. The less-handled group did not differ in the time spent head-dipping, but made more head-dips at empty holes. Both groups reacted similarly to the removal of the objects on day 4. However, the extensively handled rats showed a greater response of increased head-dipping when a novel object was introduced on day 5. The groups did not differ in their locomotor activity, but the extensively handled group made more rears. The results are discussed with respect to the neurochemical changes that have been found after repeated handling. PMID- 7862694 TI - Effects of chronic treatment with triazolam on operant responding in rats. AB - The aims of the present study were to investigate the effect of the benzodiazepine antagonist, flumazenil, on operant responding in rats treated chronically with the short-acting hypnotic triazolam and to study the consequence of chronic triazolam treatment on the time course of effects of triazolam and zolpidem. Zolpidem is an imidazopyridine with a pharmacological and behavioral profile that differs from that of the benzodiazepine hypnotics. Rats were treated with saline or triazolam (1 or 3 mg/kg) twice daily for 5 days and were tested daily 1, 3, 5.5 or 7.5 h after injection. In addition, on the 5th day of chronic treatment all rats were injected with flumazenil (10 mg/kg) 10 min before session. The time course of effects of triazolam and zolpidem was determined after cessation of repeated saline or triazolam treatment. Tolerance to the depressant effect of 1 mg/kg of triazolam developed during long-term administration. Flumazenil decreased operant responding in rats pretreated with triazolam. The effect was statistically significant when rats had received 1 mg/kg of triazolam 3 h before the session or 3 mg/kg of triazolam 3, 5.5 or 7.5 h before the session. After cessation of chronic treatment, rats pretreated chronically with 3 mg/kg of triazolam displayed decreased sensitivity to triazolam and to 10 mg/kg but not 3 mg/kg of zolpidem. The present results indicate that chronic treatment with triazolam induces tolerance to the rate decreasing effect of the drug and dependence as measured by flumazenil-induced disruption of operant responding. The limited degree of cross-tolerance between zolpidem and triazolam may suggest that their pharmacological mechanisms of action are distinct. PMID- 7862695 TI - Central effects of CCK ligands in pigs making operant responses for food. AB - The effects, on operant feeding, of intracerebroventricular (ICV) injections of the CCKA receptor agonist A71623, the CCKB receptor agonist A63387, and the CCKA receptor antagonist A70104 were investigated in prepubertal pigs. In overnight starved animals, feeding was inhibited by 20, 5, and 1 micrograms doses of A71623 and by 20, but not 5 or 1 micrograms doses of A63387. In a second experiment, although pigs pretreated centrally with A70104 (20 micrograms) showed a tendency to eat more, the effect was not statistically significant. Furthermore, this dose of A70104 did not prevent the inhibition of feeding induced by a subsequent ICV injection of CCK (1 microgram). These findings support the view that exogenous CCK reduces food intake in pigs by acting, primarily, on CCKA receptors. PMID- 7862696 TI - Effect of 1-amino-5-bromouracil on brain monoamine metabolism in rats. AB - The effect of 1-amino-5-bromouracil (ABU), a novel central-acting agent, on monoaminergic neurotransmitter levels of rat brain was investigated. Under the nonstressed condition, ABU (20 and 30 mg/kg intraperitoneally [IP]) did not affect monoamine metabolism, whereas diazepam (5 mg/kg IP) increased the 3 methoxy-4-hydroxyphenylethylene glycol (MHPG)/noradrenaline (NA) ratio. One-hour immobilization stress increased the MHPG/NA ratio in various brain regions of drug-naive rats, but did not increase the homovanilic acid (HVA) plus 3,4 dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) ratio or the 5-hydroxyindole acetic acid (5-HIAA)/serotonin (5-HT) ratio. Pretreatment with ABU or diazepam suppressed the activation of noradrenergic neurons induced by immobilization stress. By contrast, electric foot shock stress increased the MHPG/NA and HVA+DOPAC/DA ratios. Pretreatment with ABU or diazepam suppressed the activation of noradrenergic and dopaminergic cortical neurons by electric foot shock stress. These results indicate that these two physiologic stresses affected monoaminergic neurons differently and that their effects were suppressed by ABU and diazepam. PMID- 7862697 TI - Zinc inhibition of GABA-stimulated Cl- influx in rat brain regions is unaffected by acute or chronic benzodiazepine. AB - Zinc modulation of GABAA receptor function was studied using GABA-stimulated 36Cl influx into microsacs prepared from rat cerebral cortex, cerebellum and hippocampus. Zinc (10-100 microM) did not affect the basal influx, but significantly inhibited GABA-stimulated 36Cl- influx. The inhibition appeared to be noncompetitive. Zinc produced differing degrees of inhibition of GABA stimulated 36Cl- influx in different brain regions. The order of sensitivity to zinc inhibition of GABA-stimulated 36Cl- influx was hippocampus > cerebral cortex > cerebellum. These regional differences may reflect the structural heterogeneity of GABAA receptors among brain areas. Zinc inhibition was not affected by the short-term addition of three benzodiazepines, diazepam, bretazenil and triazolam. The effect of diazepam and bretazenil to potentiate GABA-stimulated 36Cl- influx was not affected by zinc, but the effect of triazolam was decreased by zinc. In brain tissue prepared from flurazepam-treated rats, there was no difference compared with controls in zinc inhibition of GABA-stimulated 36Cl- influx. The results indicate that the effects of zinc on the GABAA receptor are largely independent of drugs acting on the benzodiazepine binding site. PMID- 7862698 TI - Time-dependent effects of PCPA on social aggression in chicks. AB - We investigated the effects of para-chlorophenylalanine (PCPA), a serotonin (5 HT) antagonist, on social aggression and brain neurochemistry in young domestic chickens (Gallus domesticus). In Experiment 1, the effects of four different doses of PCPA (0, 100, 200, and 400 mg/kg) were examined for 3 days after injection. Immediately after PCPA injection, aggressive pecking was low and then increased over the 3-day test period. PCPA significantly decreased 5-HT, 5 hydroxyindoleacetic acid (5-HIAA), and 5-HT turnover. In addition, the frequency of aggression was negatively correlated with levels of 5-HIAA. In Experiment 2, the time-dependent effects of a single 400-mg/kg dose of PCPA were examined for 5 and 7 days after drug exposure. PCPA-treated chicks observed for 5 days after injection had significantly greater frequencies of aggression 4 days following drug exposure and significantly reduced 5-HT levels when measured on the next day. Similarly, chicks observed for 7 days exhibited significantly elevated aggression 5 days after injection, after which their pecking decreased to control levels on days 6 and 7. Coinciding with this behavioral pattern, 5-HT levels from these PCPA-treated chicks when assessed 7 days after drug exposure were the same as those for control birds. We concluded that PCPA increased social aggression in birds, an effect that diminished as brain 5-HT levels recovered over a 1-week period. PMID- 7862699 TI - Cardiovascular effects of NMDA and MK-801 infusion at area postrema and mNTS in rat. AB - In urethane-anesthetized male Sprague-Dawley rats, microinfusion of N-methyl-D aspartate (NMDA) into the area postrema (AP) at the dose of 10 ng produced significant decreases in mean arterial pressure (MAP) (-26 +/- 5 mmHg), heart rate (HR) (-34 +/- 6 bpm), renal blood flow, mesenteric blood flow, and iliac vascular resistance. In addition, microinfusion of the same dosage of NMDA into the medial nucleus tractus solitarius (mNTS) produced significant decreases in MAP (-33 +/- 4 mmHg), HR (-33 +/- 6 bpm), renal blood flow, mesenteric blood flow and vascular resistance, and iliac blood flow and resistance. MK-801 (dizocilpine) microinfusion alone produced no significant changes in MAP or HR when microinfused either into the AP or unilaterally into the mNTS; however, bilateral microinfusion of MK-801 into mNTS produced sustained hypertension and tachycardia, lasting about 30 min. MK-801 pretreatment at both AP and mNTS effectively blocked NMDA-induced cardiovascular responses. MK-801 microinfusion at AP significantly attenuated baroreceptor reflex-mediated bradycardia elicited by intravenous injection of phenylephrine, but did not alter reflex tachycardia elicited by intravenous nitroprusside. In conclusion, NMDA receptor-mediated neurotransmission is involved in the cardiovascular functions of both AP and mNTS. Both loci appear to be sites of action for MK-801. PMID- 7862700 TI - Differential effects of d-amphetamine on vigilance in younger and older male rats. AB - After training to comparable levels of performance on a two-choice, discrete trial vigilance task, younger (9 mo) and older (26 mo) male F344xBN rats were tested after SC injections of d-amphetamine (0.125, 0.25, 0.50, and 1.0 mg/kg). Relative to their saline treatment performance levels, both groups exhibited decreases in choice latencies under the lower doses of amphetamine and an increase in food retrieval latencies after 1.0 mg/kg amphetamine. The percentage of correct responses in the older animals was lower than in the younger animals at all doses of amphetamine, and the groups differed significantly at the 0.25 and 0.50 mg/kg doses. There were no significant differences between the groups in either of the latency measures at any of the doses of amphetamine. These results suggest, as has been demonstrated with cocaine, that the alertness-altering properties of amphetamine are qualitatively different in older and younger adult organisms. PMID- 7862701 TI - Primate performance decrements following acute soman exposure: failure of chemical countermeasures. AB - Three experiments are reported: 1) a feasibility study on using laboratory primates repeatedly in behavioral toxicity studies of organophosphate (OP) agents or of chemical countermeasures against OPs; 2) a study of the efficacy of pyridostigmine pretreatment and 2-PAM therapy; and 3) a study to determine the effects of these treatments on soman-induced cholinesterase (ChE) inhibition and its recovery. In rhesus monkeys, three repeated acute low-dose (2.1 to 2.8 micrograms/kg) soman exposures, separated by intervals > 5 weeks, did not change baseline compensatory tracking performance or the soman ED50. Atropine therapy (97 micrograms/kg) alone had no effect on soman ED50. Addition of pyridostigmine pretreatment (150 micrograms/kg) and 2-PAM therapy (17 mg/kg) to atropine therapy increased the soman ED50 for a performance decrement from 2.27 micrograms/kg to 2.58 micrograms/kg, an insignificant protective effect. At the soman ED50 for behavioral decrements, pyridostigmine pretreatment increased the inhibition of serum ChE observed immediately after soman exposure, but reduced the extent of permanent inhibition. The 2-PAM therapy reduced serum ChE inhibition from about 80% to less than 70%. These effects on the time course of ChE inhibition following soman exposure appear to combine additively. These chemical countermeasures do not prevent soman-induced performance decrements, even though they are effective in protecting lives after much higher doses. The soman doses used produce only small, transient performance decrements; animals so exposed can, thus, be used repeatedly in such studies. PMID- 7862702 TI - Are the cognitive-enhancing effects of nicotine in the rat with lesions to the forebrain cholinergic projection system mediated by an interaction with the noradrenergic system? AB - Experiments were conducted to test the hypothesis that the enhancing effect of nicotine on water maze performance in rats with lesions of the forebrain cholinergic projection systems (FCPS) is mediated by an interaction with the noradrenergic system, in particular the ascending dorsal noradrenergic bundle (DNAB) and its projection areas. Three groups of rats received lesions of either: i) the nucleus basalis (NBM) and medial septal area/diagonal band (MSA/DB) by infusion of alpha-amino-3-hydroxy-4-izoxazole propionic acid (AMPA) (FCPS group), ii) DNAB, by infusion of 6-hydroxydopamine (6-OHDA) (NOR group), or iii) both FCPS plus DNAB (COMB group). Control animals received vehicle. Choline acetyltransferase activity was reduced in the cortex and hippocampus of the FCPS and COMB groups and in the hippocampus of the NOR group. NA level was reduced in the cortex and hippocampus of the FCPS and COMB groups, but not the FCPS group. In a reference memory task, the performance of both the NOR and COMB groups, but not the NOR group, was significantly worse than that of controls; there was no effect of nicotine administration (0.1 mg/kg) on escape latency or other measures in this task. In a working memory task, FCPS and COMB rats took longer to find the submerged platform on the second and following trials, and there was a significant enhancement of performance by nicotine in both groups, but not in controls. These results indicate that the enhancing effects of nicotine in rats with FCPS lesions are not mediated by an interaction with the DNAB. PMID- 7862703 TI - Atipamezole, an alpha 2 antagonist, augments opiate-induced muscle rigidity in the rat. AB - Atipamezole is a new, highly selective alpha2-adrenoceptor antagonist currently undergoing clinical trials as an antagonist for dexmedetomidine, a potent alpha2 agonist with sedative and analgesic properties. It has previously been demonstrated that dexmedetomidine, acting at central alpha2 adrenoceptors, antagonizes opiate-induced muscle rigidity. However, the role of endogenous alpha2-adrenergic systems in opiate-induced rigidity remains to be elucidated. The present study was designed to assess the effects of atipamezole on basal muscle tone and on alfentanil-induced muscle rigidity in the rat. Muscle tone was measured using gastrocnemius electromyography (EMG). After a 15-min baseline, saline or atipamezole (0.3 or 1.0 mg/kg) was administered, and 10 min later, saline or alfentanil (50, 150, or 300 micrograms/kg) was injected subcutaneously. Data were collected for an additional 60 min. Atipamezole (1.0 mg/kg) pretreatment (in the absence of alfentanil) produced a small increase in tonic EMG activity when compared with saline pretreatment. After saline pretreatment, significant muscle rigidity occurred in the two highest alfentanil dose groups. Atipamezole (0.3 and 1.0 mg/kg) augmented alfentanil-induced muscle rigidity. The ability of the alpha2 antagonist to potentiate both basal muscle tone and alfentanil-induced rigidity suggests that endogenous adrenergic activity and/or direct alpha2-adrenoceptor interaction with opioid receptors mediate opiate induced muscle rigidity. These findings may be of clinical as well as basic neuropharmacological interest. PMID- 7862704 TI - Individual differences in sensitivity to nicotine in mice: response to six generations of selective breeding. AB - Four hundred seventeen heterogeneous stock mice were tested for their relative sensitivity to a low dose of nicotine (0.75 mg/kg) using activity in an automated Y-maze and body temperature as response measures. A wide spectrum of individual responsiveness to nicotine, ranging from complete suppression of activity to stimulation above baseline activity, was found. Replicate measures taken 1 week later on the same animals showed the responses to nicotine to be reliable and reproducible. Activity levels and body temperatures following nicotine administration were highly correlated (r = 0.60, df = 415). From analysis of between-litter proportions of variance, the heritability of nicotine-influenced activity was estimated to be 0.12, indicating that selective breeding for differential responsiveness to nicotine would be possible. The 10 most activated and 10 most depressed male and female mice were chosen as breeders for replicate nicotine activated (NA) and nicotine depressed (ND) lines, respectively. The selection criterion was nicotine-induced activity corrected for baseline activity using regression residuals. After six generations of selective breeding a good response to selection was obtained, although the response was better for the ND than for the NA lines. Realized heritability for responsiveness to nicotine calculated from the six selected generations was found to be 0.20, or slightly greater than that estimated from the foundation population. There were no significant differences in response to selection between the replicate NA or ND lines. Nicotine-induced body temperature was measured as a correlated response to selection, and was found to remain highly correlated with nicotine-induced locomotor activity. The response was more robust for the ND lines than it was for the NA lines. In contrast to the large differences between the ND and NA lines in locomotor activity and body temperatures following nicotine administration, mean baseline activities and body temperatures remained nearly identical throughout. This indicates that selection acted specifically on nicotine-induced responses, and not on baseline measurements, as predicted for response to a selection criterion based on regression residuals. PMID- 7862705 TI - Social interactions in rats: behavioral and neurochemical alterations in DSP-4 treated rats. AB - Noradrenergic neurotoxin DSP-4, preceded by zimelidine to prevent serotonin depletion, was administered IP to rats behaving in a defensive-submissive manner in a resident-intruder paradigm. Computer-based ethological analysis revealed the decrease of frequency and duration of defensive episodes and marked increase of offensive aggression. This might suggest an increase of aggressiveness and therefore support the notion of an inhibitory role of the noradrenergic system in aggressive behavior independently of the model used. Dramatically changed attitude toward the partner might also result from fear reduction or inadequate responsiveness to environmental factors because DSP-4-treated rats explored more than controls in stressogenic, highly illuminated area. HPLC analysis showed significant reduction of noradrenaline (NA) concentration in amygdala, hypothalamus, hippocampus, and frontal cortex. Simultaneously there occurred a considerable decrease in dopamine (DA) and serotonin (5-HT), and their metabolite levels. This suggests an attenuated activity of the DA and 5-HT systems that we consider as an effect secondary to NA depletion, which reflects the functional interactions between DA, 5-HT, and NA systems. PMID- 7862706 TI - The elevated T-maze: a new animal model of anxiety and memory. AB - In an attempt to analyze different types of anxiety, and at the same time assess memory, a new experimental model was developed. The apparatus, named the elevated T-maze, consisted of three arms of equal dimensions (50 x 10 cm) elevated 50 cm from the ground. One arm, enclosed by 40-cm high walls, was perpendicular to two open arms. The first experimental session was conducted 25 min after IP injection of either drug or saline. To assess inhibitory (passive) avoidance, the rat was placed at the end of the enclosed arm and the time taken to withdraw from this arm was recorded three times in succession. Soon afterwards, the rat was placed at the end of one of the open arms and the time taken to withdraw from this arm was measured, thus estimating one-way escape. To assess memory, inhibitory avoidance and escape were measured again 3 days later, without drug. Dose response curves were determined for the benzodiazepine anxiolytic and amnestic agent diazepam (DZP, 0.5-4 mg/kg), as well as for ipsapirone (IPS, 0.25-2 mg/kg), an azapirone anxiolytic that is devoid of clinically significant amnestic effects. The doses of 1, 2, and 4 mg/kg DZP and of 1 and 2 mg/kg IPS impaired inhibitory avoidance, an effect that may be viewed as anxiolytic. Inhibitory avoidance remained impaired 3 days later in the rats treated with 1-4 mg/kg DZP, indicating anterograde amnesia. This effect was not due to state-dependent learning, because rats injected both at pretraining and pretesting with 2 mg/kg DZP still showed complete amnesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862707 TI - Habenula lesions decrease the responsiveness of dorsal raphe serotonin neurons to cocaine. AB - The median and dorsal (MR and DR) raphe nuclei are the origin of serotonin (5-HT) containing neurons that innervate the forebrain. Neurons originating in the medial and lateral habenula provide an extensive afferent input to the midbrain that could serve as a negative feedback circuit. The present study was undertaken to establish whether intact habenula nuclei are required to observe the depressant effects of cocaine on the neural activity of 5-HT somata in the DR. To this end, the spontaneous activity of DR 5-HT neurons was assessed in male rats that had previously received bilateral radiofrequency lesions of the habenula complex either 1-4 h (short term) or 7 days (long term) prior to extracellular recordings of single 5-HT neurons of the DR. In rats with short-term lesions, the inhibitory response to cocaine was significantly attenuated. The mean dose to inhibit activity by 50% (ID50) was increased from 0.68 mg/kg in controls to 2.5 mg/kg in lesioned rats. Short-term habenula lesions also significantly decreased the numbers (but not the firing rates) of 5-HT neurons encountered in the DR. In contrast, the dose-response to cocaine as well as the numbers and firing rates of 5-HT neurons found in rats with long-term habenula lesions did not differ from controls. These results suggest that the inhibitory effects of cocaine on DR 5-HT neuronal activity depend in part on the ability of cocaine to affect habenula control of raphe 5-HT function. PMID- 7862708 TI - The effects of GABAB ligands on alcohol withdrawal in mice. AB - Recent research suggests that the GABAB receptor may mediate some of the acute effects of alcohol, but little is known of its involvement in alcohol withdrawal. Mice made dependent on alcohol exhibited tremor and tail arch when consumption ceased. Diazepam dose-dependently attenuated both tremor and tail arch, whereas baclofen had no effect on either of these two withdrawal symptoms. However, baclofen dose-dependently induced convulsant behaviour in the withdrawing mice, and this was significantly attenuated by the GABAB antagonists phaclofen (50 mg/kg) and CGP 35348 (300 mg/kg), but not BPBA (50 mg/kg). Phaclofen, BPBA, and CGP 35348, when administered alone and in combination with a single dose of baclofen, did have an effect on tremor, although the magnitude was small in comparison to that seen with diazepam. It appears that the GABAB receptor may play a role in mediating convulsions during alcohol withdrawal, and that in this system baclofen is proconvulsant. PMID- 7862709 TI - Characterization of the binding of SCH 39166 to the five cloned dopamine receptor subtypes. AB - Characterization studies were conducted on the five cloned dopamine receptor subtypes (D1-D5) using the novel D1-selective antagonist, SCH 39166, as well as other related benzazepines and dopaminergic agents. The results demonstrate that SCH 39166 exhibits saturable, high-affinity binding to the D1 and D5 receptors, but binds with low affinity to the D2, D3, and D4 receptors. In contrast, the D2 antagonist haloperidol showed low affinity for the "D1-like" receptors and high affinity for the "D2-like" receptors. A series of agonists was also evaluated and the D5 receptor subtype displayed a two-site fit for the endogenous agonist dopamine, as well as for the agonist apomorphine. Differences in agonist binding among the D1-like receptors reflect the importance of the nonconserved amino acid substitutions. PMID- 7862710 TI - Effects of naloxone on the subjective and psychomotor effects of nitrous oxide in humans. AB - The effects of naloxone on the mood-altering and psychomotor-impairing effects of nitrous oxide were examined in two studies. Each of the double-blind, randomized trials tested effects of three doses of naloxone or saline placebo during inhalation of 30% nitrous oxide in oxygen or 100% oxygen placebo. Experiment 1 tested a range of naloxone doses used clinically to reverse opiate-induced respiratory depression (0, 0.01, 0.1 1.0 mg/70 kg) and Experiment 2 included a dose approximately 25 times higher than that needed to reverse opiate-induced respiratory depression (0, 1.0, 3.0, 10 mg/70 kg). Nitrous oxide increased subject-rated reports of "feel drug effect," "carefree," "drunk," "sedated," and "high", and decreased psychomotor performance in both experiments. Naloxone had no effects by itself in either experiment, and, for the most part, did not significantly interact with nitrous oxide-induced changes in mood or psychomotor performance. Naloxone, in doses of 10 mg or less, does not appear to affect the subjective and psychomotor effects of nitrous oxide. PMID- 7862711 TI - Opioidergic receptors in the arcuate nucleus are not involved in the cardiovascular effects of clonidine. AB - The arcuate nucleus is the bed nucleus for the pro-opiomelancortin system of the brain with important connections with other nuclei involved in cardiovascular function. Clonidine has been reported to produce its cardiovascular effects through an interaction with opioid and alpha 2-adrenergic receptors. The present study examined the arcuate nucleus as a site of action of clonidine. Male spontaneously hypertensive rats were anesthetized with pentobarbital and were instrumented for the measurement of blood pressure and heart rate. Cannulae were placed either through the cisterna magna (IC) or in the arcuate nucleus. Administration of clonidine (0.03-3.75 micrograms, IC) produced a dose-dependent hypotension and bradycardia. Pretreatment with naloxone (30 micrograms, IC) prior to clonidine administration resulted in a significant attenuation of both the clonidine-induced hypotension and bradycardia. In contrast, administration of naloxone (100 ng) into the arcuate nucleus prior to the central administration of clonidine did not alter the cardiovascular effects of clonidine. These results support the role of central opioidergic receptors in the cardiovascular effects of clonidine but do not support the arcuate nucleus as the site of action. PMID- 7862712 TI - Lack of evidence for context-dependent cocaine-induced sensitization in humans: preliminary studies. AB - Cocaine-induced behavioral sensitization is the well-documented phenomenon where repeated doses of cocaine elicit increasingly greater effects on motoric activity in rats. Some observations suggest that behavioral sensitization may provide a model for understanding the mechanisms of drug-craving elicited by environmental triggers or cues. The process of fully validating such an animal model for its ability to detect effective anticraving medicines is a difficult and long-term undertaking. As a first step in that direction, we decided to determine if cocaine can produce conditioned behavioral sensitization in humans using a paradigm fairly similar to that used for rodents. Because humans do not react to cocaine with the pronounced motor activation observed in rodents, we measured a variety of end points, including blood pressure (BP), heart rate (HR), respiratory rate, pupil diameter, hormones (prolactin and cortisol), and subjective responses using the questionnaire for drug-related feelings (QDRF) and the EEG. To mimic the home and test cages used in rodent studies, two rooms were used: a small test chamber and a regular room with a window and furnishings. On day 1 each subject received a drug infusion (either saline or 40 mg cocaine IV) in both locations. On day 2, all subjects received an infusion (saline or 25 mg cocaine IV) in the test chamber. All drug infusions were conducted double blind. The paired group received cocaine on both days in the test chamber. The unpaired group received cocaine in regular room on day 1, and cocaine in the test chamber on day 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862713 TI - GABA receptor-linked chloride channels and the behavioral effects of naltrexone in rats. AB - The present study was conducted to determine whether the effects of naltrexone on schedule-controlled behavior in rats were mediated, at least in part, by the GABAergic system. Because the enhanced sensitivity that has been shown to occur following naltrexone treatment might alter the effects of the treatment compounds, a variety of compounds interacting with the GABA system were tested in both sensitized and nonsensitized animals. Of all the compounds tested in this manner, only the dose-effect function for the GABA agonist muscimol was altered by the naltrexone treatment, with the higher doses of muscimol producing response rate decreasing effects only in naltrexone-sensitized rats. In the naltrexone treated animals, these same GABA agonists and antagonists were used as pretreatments prior to the determination of the naltrexone dose-effect function. Although shifts in the naltrexone dose-effect function were observed, the effects were not consistent either within or across receptor class. In contrast, the chloride-channel antagonist picrotoxin clearly shifted the naltrexone dose-effect function in sensitized animals to the left, while the chloride-channel facilitator pentobarbital shifted the function to the right. These results indicate that the effects of naltrexone are at least partially mediated by an action at the GABA-linked chloride channel, rather than directly at the GABA receptor. PMID- 7862714 TI - Influence of chronic aminophylline on antielectroshock activity of diazepam and aminophylline-induced convulsions in mice. AB - The effects of chronic administration of aminophylline (AMPH; 50 mg/kg, twice daily for 14 consecutive days) were studied on both antielectroshock efficacy of diazepam (DZP) and convulsive activity of AMPH in mice. AMPH injected acutely at a dose of 50 mg/kg significantly reduced anticonvulsant action of DZP elevating ED50 from 10.9 (control) to 15.9 mg/kg (p < 0.01). After the administration of AMPH for 3 days, ED50 value was still higher compared with control. Chronic treatment with AMPH resulted in further increase of ED50 of DZP, which was 20.2 mg/kg, and this elevation was significant not only when compared with saline treated animals, but also with acute and 3-day administration of the xanthine (p < 0.01, 0.05, and 0.001, respectively). Therefore, no tolerance to this AMPH mediated effect was found, and even an enhancing influence was observed. On the other hand, chronic treatment with AMPH decreased convulsive activity of AMPH elevating ED50 for induction of clonic seizures from 218 to 252 mg/kg (p < 0.01). The remaining seizure parameters were unaffected. Furthermore, in both cases pharmacokinetic interactions were excluded, at least in terms of total plasma levels of the drugs. The results suggest that the mechanisms governing AMPH induced reversal of the anticonvulsant efficacy of DZP qualitatively differ from those underlying AMPH-induced convulsions. Moreover, these data support the claim that AMPH should be avoided in patients suffering from different types of epilepsy. PMID- 7862715 TI - The alkylating properties of chlorambucil. AB - Previous work has indicated an aziridinium ion mechanism in the hydrolysis of chlorambucil, and the present work on the alkylation of nucleophiles fully supports this mechanism. This mechanism forms the basis for understanding the kinetics of alkylation reactions because their rates are limited by the rate of formation of the aziridinium ion and the alkylation reaction competes with the hydrolytic reaction. We have measured alpha N, where alpha N(N) is the rate of reaction of the aziridinium ion with a nucleophile N relative to its reaction with water for several nucleophiles that are related to those found in proteins. The alpha values for hydroxide ion and some other bases are greater than 10(3), but the effective values at pH 7.5 are much smaller because there is little base present. The kinetic equations show that it is very difficult to alkylate a nucleophile extensively at pH 7.5 before chlorambucil has hydrolyzed. Therefore, it is not clear why angiotensin-converting enzyme is completely inhibited by low concentrations of chlorambucil. On the other hand, damage to DNA is easily understood. PMID- 7862716 TI - Receptor binding in Japanese quail selected for long or short tonic immobility. AB - Japanese quail, selectively bred for long (LTI) and short (STI) tonic immobility (TI) responses, are thought to represent high and low fear groups, respectively. To study the neurochemical mechanisms underlying the behavioral distinctions, binding parameters were determined at the benzodiazepine, 5-HT1A, 5-HT3, alpha 2, and opioid receptor sites in the forebrains of the two lines. No differences were found in 5-HT1A, 5-HT3, alpha 2, mu- or kappa-opioid receptor binding between the lines. The KD for the binding of [3H]-flunitrazepam at the benzodiazepine receptor was significantly greater in the LTI than in the STI birds, indicating lower affinity for benzodiazepine ligands. The lines did not differ in benzodiazepine receptor number. Using [3H]-naltrindole, the LTI line was found to have fewer delta-opioid receptors than the STI line; the birds did not vary with respect to the affinity of these receptors. Thus, the selective breeding of the two lines has resulted in differences in benzodiazepine and delta-opioid binding, and these could produce differences in activity levels, fear, and pain responses, all of which could contribute to the tonic immobility response. PMID- 7862717 TI - Effect of spontaneous alcohol intake on heart rate and dietary intake of free living women. AB - Moderate alcohol consumers obtain excess calories from alcohol and these additional calories do not result in weight gain. This study examined the contribution of alcohol to the total caloric intakes and expenditures of light to moderate alcohol consumers and compared the data to soda drinkers. Physical activity levels were measured by employing continuous heart rate monitoring for a 6-day normal phase and a 6-day abstinence phase. The normal food intake of both groups was recorded in diet diaries. Subjects' overall intake of food energy during the alcohol week was significantly higher than during any of the other three phases (an excess of 241 kcal/day). This study suggests that excess alcohol calories are compensated by an increase in energy expenditure, as evidenced indirectly by increased heart rates occurring between the hours of 2300 and 0700 h, increased self-reported nightly restlessness, increased wake time, and exercise. PMID- 7862718 TI - New technique for cannulae implantation into the dorsal raphe nucleus using layer 5 of cerebellum reference in rat stereotaxic surgery. AB - A new surgical method for needle or electrode implantation using layer 5 of the cerebellum (C5) as anatomical reference in rat stereotaxic surgery was developed. The coordinates of the new technique for electrode or needle implantation into dorsal raphe nucleus (DRN) are: PA: 3.20-340 mm, V: 6.00-6.40 mm, and L: 0.00 mm. The success of the new surgical procedure was confirmed by histological control of the lesion impact of the electrode into NRD. This lesion impact was well positioned in 83-86% of implanted rats. The use of this method can be extended to other nuclei than the DRN of the brain for cannula implantation. In addition, it can be used in rats on a larger scale, because it suppresses the limitations due to age and body weight. PMID- 7862719 TI - Preference for high- versus low-potency marijuana. AB - With many drugs of abuse, humans and other species display a preference for higher doses (or more potent dosage forms) over lower doses (or less potent dosage forms). The present study was designed to determine whether this generalization would hold for marijuana smoking by humans. Twelve regular marijuana smokers participated in two independent and identical choice trials in which, on separate sessions, they first sampled marijuana of two different potencies (0.63% and 1.95% delta-9-tetrahydrocannabinol; THC) and then, on the next session, chose which of the two, as well as how much, to smoke. During sampling sessions, the high-potency marijuana produced a greater heart rate increase and greater subjective effects than the low-potency marijuana. Subjects chose the high-potency marijuana significantly more often than the low-potency marijuana (21 out of 24 choice occasions). These results support the hypothesis that the reinforcing effects of marijuana, and possibly its abuse liability, are positively related to THC content. PMID- 7862720 TI - Tolerance development to butorphanol: comparison with morphine. AB - In order to evaluate and to compare the time course, dose response, and the degree of tolerance development to butorphanol and morphine, rats were continuously intracerebroventricularly (ICV) infused with saline vehicle (1 microliter/h), butorphanol (6.5, 13, 26, and 52 nmol/microliters/h), or morphine (1.6, 6.5, and 26 nmol/microliters/h) through osmotic minipumps for 1 to 3 days. The tail-flick responses were determined pre-, during, and postinfusion. Tolerance to morphine developed faster than that to butorphanol. The antinociceptive response to the ICV challenge dose (6 h after the termination of drug infusion) of butorphanol or morphine was decreased significantly and there was a negative correlation between the dose of the drug infused and the observed antinociceptive response. In terms of butorphanol and morphine tolerance, a parallel rightward shift in the dose-response curve was produced with the degree of shift proportional to the log of the infusion dose. In tail-flick tests, the shifts of the dose-response curves for butorphanol and morphine in tolerant animals were 11.8- and 46.3-fold, respectively. However, in the acetic acid writhing test, the shifts of the dose-response curves for butorphanol and morphine in tolerant animals were 11.3- and 11.7-fold, respectively. These results suggest that there is a greater degree of tolerance to morphine than there is to butorphanol, but the degree of butorphanol tolerance is still substantial. In addition, two pain assays (tail flick vs. writhing) yielded different estimations of tolerance in a comparison of morphine and butorphanol. PMID- 7862721 TI - Crosstolerance between butorphanol and morphine in rats. AB - To investigate the antinociceptive effects of morphine and U-50,488 after continuous administration with butorphanol, rats were intracerebroventricularly (ICV) infused with butorphanol (26 nmol/microliters/h) through osmotic minipumps for 3 days. Six hours after termination of infusion, the rats were challenged with different doses of morphine or U-50,488. Antinociceptive effects, as assessed by tail-flick and acetic acid writing tests, were measured 15 min after challenge. Development of crosstolerance to morphine was evident in butorphanol infused animals. The study also revealed that crosstolerance to butorphanol developed in continuously ICV morphine-infused animals. Continuous ICV infusion with butorphanol produced a marked rightward shift of the antinociceptive dose response curve resulting from U-50,488 challenge. These results showed that there is an antinociceptive crosstolerance between butorphanol and morphine, and crosstolerance to U-50,488 developed in continuously butorphanol-infused animals. The present data suggested that chronic ICV treatment with high doses of butorphanol can lead to desensitization of the antinociceptive systems mediated through the central kappa as well as mu receptors in rats. PMID- 7862722 TI - Possible genetic factors underlying the pathophysiology of tardive dyskinesia. AB - Rates of spontaneous and drug-induced repetitive jaw movements (RJM) in rats vary widely. Low and high RJM responders were isolated and genetically selected. At each generation mean RJM responses (spontaneous or SKF 38393-induced) of the two types of rats were found to differ significantly, whereas neither apomorphine induced stereotypic responses nor D1 and D2 receptor numbers and affinities differed. A significant increase in cAMP production was evident in SKF 38393 stimulated striatal homogenates of high RJM responders as compared with low responders. Animals subjected to 8-months exposure to fluphenazine exhibited RJM that were about twice as great as that of controls, 2 months after the last treatment, with a prevalence of about 75%. Similarities between RJM observed in rats and neuroleptic-induced tardive dyskinesia suggest that the two are strongly related. PMID- 7862723 TI - [D-Pen2-D-Pen5]enkephalin, a delta opioid agonist, given intracerebroventricularly in the mouse produces antinociception through medication of spinal GABA receptors. AB - Intracerebroventricular (ICV) administration of [D-Pen2-D-Pen5]enkephalin (DPDPE), a delta opioid receptor agonist, activates a descending antinociceptive pathway that inhibits the tail-flick response in mice. Involvement of spinal GABA receptors in this response was studied by giving GABA antagonist intrathecally. First, antinociception produced by intrathecally administered isoguvacine, a GABAA agonist, was inhibited by intrathecal bicuculline (GABA receptor antagonist) or picrotoxin (chloride channel antagonist). Then, antinociception induced by ICV DPDPE was antagonized by intrathecal picrotoxin and bicuculline in a dose-and time-dependent manner. Second, intrathecal administration of 2 hydroxysaclofen, a GABAB antagonist (which inhibited antinociception induced by a GABAB agonist, baclofen, given IT), produced a shift of the dose-response curve for ICV DPDPE to the right. GABAA agonist, baclofen, given IT), produced a shift of the dose-response curve for ICV DPDPE to the right. GABAA and B antagonists given together intrathecally produced a greater than additive antagonistic effect against ICV DPDPE-induced antinociception. Thus, the delta agonist action of DPDPE in the brain leads to activation of descending spinal pathways which involve mediation by spinal GABAA and GABAB receptors in the antinociceptive response. PMID- 7862724 TI - Effects of piracetam on indices of cognitive function in a delayed alternation task in young and aged rats. AB - The effects of piracetam (64, 128, and 256 mg/kg PO) on the performance of a delayed alternation in a Skinner Box were investigated. Test sessions consisted of 36 trials during which animals were first presented with a single lever (left or right) followed 5, 10, or 20 s later by two levers. A press on the lever opposite to that presented previously (nonmatching to sample) was rewarded. The number of correct responses and the reaction times to the one- and two-lever presentations were recorded. All animals received all treatments in a balanced order. Aged animals showed clear deficits on all three parameters. Piracetam was without effect on the performance of young animals but dose-dependently decreased the choice reaction times (two levers) in aged animals without affecting the other two parameters. These results suggest that piracetam does not affect short term memory but may facilitate choice behavior in aged animals. PMID- 7862725 TI - Effects of intraseptally injected glutamatergic drugs on hippocampal sodium dependent high-affinity choline uptake in "naive" and "trained" mice. AB - We have previously reported that spatial reference memory (RM) training-induced alterations in hippocampal cholinergic activity as measured by sodium-dependent high-affinity choline uptake (SDHACU). Each training session was found to induce an immediate (30 s) increase in SDHACU followed (30 s to 15 min posttest) by a deactivation and long-lasting inhibition (15 min to 24 h) of this cholinergic marker. The present experiments were designed to assess the role of septal glutamatergic receptors in this posttraining cholinergic deactivation. In the first experiment, the effects of intraseptal injections of different doses of glutamic acid and glutamatergic antagonists (kynurenic acid, KYN, and AP5) on hippocampal SDHACU were studied in awake but otherwise resting (i.e., naive) mice. The results showed that glutamic acid at the lowest dose used (5 ng) produced a decrease in SDHACU, whereas both glutamatergic antagonists produced a dose-related increase in this cholinergic marker. It was concluded that septal glutamatergic receptors mediate a tonic inhibitory input on the cholinergic cells. Hence, in a second experiment the effect of intraseptal injections of KYN (5 ng) on the training-induced changes in hippocampal cholinergic activity were assessed following variable amounts of radial maze RM training. Trained mice were injected 20 min before the first or the ninth training session and killed 30 s or 15 min posttraining for determination of SDHACU. KYN slowed the posttesting cholinergic deactivation (disinhibition), this effect being more marked in good learners than in bad learners. The present findings suggest that septal glutamatergic receptors mediate an inhibitory input on the cholinergic cells, and that this input could play a role in memory consolidation. PMID- 7862726 TI - NGF effects on hot plate behaviors in mice. AB - Adult CD-1 male mice were injected intravenously with 2.5 micrograms/g of highly purified murine NGF and then assessed for hot plate responding (52 degrees C) at 15, 30, 60, 180, and 360 min (repeated test) or at 30, 60, or 360 min (single test, i.e., exposure to hot plate only once). Control animals received cytochrome c (2.5 micrograms/g). In the repeated test, NGF produced hyperalgesia, increasing the number of jumps (particularly at 30 and 60 min postinjection), while in the single test the pain reaction of NGF-treated animals remained unaffected. Sensitization of C-fibers in the periphery or release of bioactive mediators from mast cells may account for NGF-induced changes in nociception. PMID- 7862727 TI - Milacemide treatment in mice enhances acquisition of a Morris-type water maze task. AB - The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor appears to be involved with processes of learning and memory. A neutral amino acid binding site is known to exist on the NMDA complex. Glycine binds with high affinity to this site and has been found to potentiate NMDA activity. 2-N-Pentylaminoacetamide HCl (milacemide) is a glycine agonist that has been found to enhance performance of rodents in passive and active avoidance tasks and has improved the performance of humans in several word retrieval tasks. We evaluated the effects of milacemide on the performance of male C57BL/6J mice in a complex spatial task, the Morris water maze. Because NMDA receptor activation appears involved in induction of long-term potentiation, it was hypothesized that milacemide administration would be involved in task acquisition. Therefore, mice were treated with either milacemide (10 mg/kg) or vehicle 1 h prior to training on each of 4 consecutive days. Results indicated that mice treated with milacemide learned the task significantly faster than controls over 4 days of training, as measured by mean distance (cm) to reach the goal platform. Therefore, agonism of the glycine site on the NMDA receptor appears to facilitate performance of learning in a spatial memory task. PMID- 7862728 TI - Ibogaine modulates cocaine responses which are altered due to environmental habituation: in vivo microvoltammetric and behavioral studies. AB - Ibogaine, a serotonergic (5-HTergic) indole alkaloid, was studied for cocaine modulatory effects on four parameters of behavior by computerized infrared photocell beam detection. The behavioral parameters were: a) locomotor activity (ambulations), b) rearing, c) stereotypy (fine movements, primarily grooming), and d) agoraphobia [(thigmotaxis) a natural tendency to avoid the center of the behavioral chamber]. With each behavioral data point, dopamine (DA) release, and serotonin (5-HT) release were detected within seconds in nucleus accumbens (NAcc) of the same behaving male Sprague-Dawley rats, using in vivo electrochemistry (voltammetry). Ibogaine was administered (40 mg/kg IP) for 4 consecutive days. Importantly, the DAergic and the 5-HTergic responses to (SC) cocaine and two behavioral responses, ambulations and central ambulations, were reduced in intensity due to extended time spent in the novel behavioral chamber (habituated). Rearing and fine movement patterns were not habituated. The results show that ibogaine downmodulated the (SC) cocaine-induced increase in NAcc DA release (p < 0.0001) and potentiated the (SC) cocaine-induced decrease in NAcc 5 HT release (p < 0.0001). Concurrently, ibogaine downmodulated cocaine-induced ambulation (p < 0.0001) and central ambulation behavior (p < 0.0001). On the other hand, the behavioral parameters that did not exhibit habituation, i.e., rearing behavior and fine movement behavior, were not downmodulated by ibogaine (p < 0.1558) (p < 0.3763), respectively. Furthermore, ibogaine itself did not significantly alter NAcc DA release over the 2-h period studied (p < 0.9113) although individual time points were significantly affected bidirectionally. Concurrently ibogaine significantly increased 5-HT release (p < 0.0155). Behaviorally, ibogaine appears to be a weak psychostimulant. The data show a critical modulatory role for 5-HT in ibogaine-cocaine interactions. Also elucidated as critical is the efficacy of ibogaine when the response to (SC) cocaine is decreased due to the habituation of the animals to their environment. PMID- 7862729 TI - Corticosterone influences forced swim-induced immobility. AB - The effect of corticosterone (CS) synthesis inhibition with metyrapone-a blocker of the 11 beta-hydroxylase (150 mg/kg IP)-on immobility time during the forced swim test was recorded. Immobility time was measured during a 15-min forced swim (test). Twenty-four hours later rats were subjected to an additional 5 min forced swim (retest). In one experiment, metyrapone or vehicle was administered 3 h before the initial test, while CS (0, 5, 10, or 20 mg/kg SC) was administered 1 h prior to the initial test. Metyrapone significantly reduced immobility time during both test and retest. This effect was reverted in a dose-dependent fashion by CS. In a second experiment, animals exposed to the initial test 24 h before were injected with metyrapone or vehicle 3 h before the retest, while CS (0, 10, or 20 mg/kg SC) was administered 1 h prior the retest. Metyrapone, administered before the retest, reduced immobility time and CS partially reverted metyrapone effect. In another group of animals, serum CS concentrations were evaluated before and after test and retest. In vehicle groups, the high immobility time during test and retest was associated with high CS serum concentrations poststress. In animals receiving metyrapone prior to the initial test, the reduced immobility time was related to low levels of CS after the test and an attenuated secretion following the retest. Moreover, CS (20 mg/kg) and metyrapone+CS groups had high CS levels before the test, which remained high 2 h after the test, although after the retest, both groups showed a pattern of CS secretion similar to that observed in vehicle animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862730 TI - Effects in the rat of intranigral morphine and DAGO on eating and gnawing induced by stress. AB - Stress produced by pinching the tail is known to increase feeding behavior in rats, and endogenous opioids have been implicated in the mediation of this effect. We have reported previously that a nonspecific opioid antagonist and a mu selective antagonist decrease this stress-induced eating (SIE) when they are microinjected into the substantia nigra (SN). The present study investigated the possibility that activation of opioid receptors in the SN might also alter SIE. Because oral stereotypy and nociception are affected by opioid mechanisms in the SN, measurements of gnawing and of tail flick and hot plate response latencies were also made. Bilateral injection of morphine (0.1-20 nmol) and the mu selective agonist D-Ala2,N-Me-Phe4,Gly5-ol-enkephalin (DAGO; 0.03-1 nmol) increased response latency on the hot plate test and decreased gnawing produced by tail pinch. Tail flick latency and SIE were not affected. It is concluded that activation of opioid receptors in the SN does not produce an alteration in SIE as has been seen with opioid antagonists. PMID- 7862731 TI - Food carrying in rats is blocked by the putative anxiolytic agent buspirone. AB - The effects of the putative anxiolytic agent buspirone on food-handling behavior of laboratory rats were investigated. Rats trained to travel from a covered shelter to a food source were provided with food pellets of six sizes. Smaller pellets were eaten at the exposed food source, whereas larger pellets were carried back to the shelter for consumption. Subcutaneous administration of buspirone hydrochloride (0.2-2.0 mg/kg) reduced carrying of larger food pellets in a dose-dependent manner. Instead, these pellets were also eaten at the exposed food source. Carrying was maximally suppressed 1 h after drug administration. Handling of smaller pellets, travel times, and eating times were not affected by buspirone. Similar results have previously been obtained with diazepam. Buspirone appears to exert its effects through 5-HT1A and/or dopamine receptors, whereas diazepam interacts with benzodiazepine receptors. Thus, manipulations of distinct transmitter systems may have similar behavioral consequences on the food carrying responses of rats. PMID- 7862732 TI - 24-hour control of body temperature in the rat: II. Diisopropyl fluorophosphate induced hypothermia and hyperthermia. AB - Diisopropyl fluorophosphate (DFP) and other anticholinesterase (antiChE) agents have been found to induce marked hypothermic responses in laboratory rodents. To characterize the effects of DFP on autonomic and behavioral thermoregulation, rats of the Long-Evans strain were injected with DFP while housed in a temperature gradient. The gradient allowed for the measurement of selected ambient temperature (Ta) and motor activity (MA) over a 6- to 7-day period. Core temperature (Tc) and heart rate (HR) were also monitored simultaneously using radiotelemetry. Injection of the peanut oil vehicle led to transient elevations in Tc, HR, and MA, but no change in selected Ta. The next day animals were injected with 0.25, 1.0, or 1.5 mg/kg DFP. DFP (1.0 AND 1.5 mg/kg) led to a marked reduction in Tc. The decrease in Tc was accompanied by reductions in HR, MA, and selected Ta. During the first night after DFP, selected Ta remained elevated as Tc recovered to its preinjection level. The second 24-h period after 1.0 and 1.5 mg/kg DFP was associated with a significant elevation in the daytime Tc. In conclusion, with the option of using behavioral thermoregulatory responses, the hypothermic effects of acute DFP treatment are mediated by a selection for cooler TaS. An elevation in Tc during recovery from acute DFP corroborates the many incidents of fever in humans exposed to anti-ChE agents. PMID- 7862733 TI - Benzodiazepine receptor mediation of the anxiolytic-like effect of (-)-nicotine in mice. AB - The anxiolytic-like effect of (-)-nicotine (1.9 mumol/kg, IP) on the elevated plus-maze in CD1 mice was blocked by the benzodiazepine receptor antagonist flumazenil (1 and 10 mumol/kg, IP). On the other hand, the cholinergic nicotinic channel blocker mecamylamine (1 to 15 mumol/kg, IP), did not affect the anxiolytic-like properties of diazepam in the same test. These data suggest that the reduction in anxiety induced by (-)-nicotine occurs indirectly via the release of endogenous substances that can activate the benzodiazepine receptor. PMID- 7862734 TI - Enhanced anorexic responses to m-chlorophenylpiperazine during lithium administration to fawn-hooded rats. AB - In the present study, we investigated whether functional adaptational changes in the serotonergic neurotransmitter mechanisms regulating food intake following long-term lithium treatment in Fawn-Hooded rats (a rat strain suggested to represent a genetic model of depression) were different or similar to those previously observed in Wistar rats. Long-term (21-25 days) lithium treatment accentuated m-chlorophenylpiperazine (m-CPP, a 5-HT agonist) induced decreases in food intake. There was no significant difference in either brain m-CPP concentrations or hypothalamic norepinephrine, dopamine and 5-hydroxyindoleacetic acid concentrations between control and long-term lithium-treated rats following m-CPP. However, hypothalamic serotonin concentrations were significantly higher in long-term lithium-treated compared to saline-treated animals. This finding contrasts with our previous report demonstrating attenuation of m-CPP-induced anorexia in Wistar rats following similar long-term lithium treatment, and therefore suggests a differential adaptation in the serotonergic neurotransmitter mechanisms regulating food intake in a genetic animal model of depression. PMID- 7862735 TI - Effects of delta 9-tetrahydrocannabinol and social context on marijuana self administration by humans. AB - The effects of time of day and social context on daily patterns of marijuana self administration were examined in two groups of three adult male marijuana smokers during a 12-day residential study. Days were divided into 6.5-h work and social access periods. Order of occurrence (i.e., work before social access or social access before work) was counterbalanced between groups and reversed for both groups on day 8. Up to eight marijuana cigarettes (0.0% or 2.3% delta 9-THC) could be smoked each day. Stable patterns of marijuana smoking were observed across days for each subject. Three subjects smoked more marijuana during the social-access period, regardless of when it occurred. The other three smoked more marijuana during the first period, regardless of whether it was a work or social access period. The number of marijuana cigarettes smoked was unrelated to THC content. In contrast, subjective reports of "High," "Liking," "Potency" and "Drug" on visual-analog scales were increased on active marijuana days. Subjective reports of drug effects were not predictive of drug self administration. PMID- 7862736 TI - Nicotine improves cognitive disturbance in senescence-accelerated mice. AB - Senescence-accelerated mice (SAM), a murine model of age-related deterioration in learning ability, were studied as to the acetylcholine (ACh) contents in the brain tissues and the effect of nicotine administration. We found that the ACh content of SAM-P/8 (accelerated senescence-prone) mice was lower than that of SAM R/1 (accelerated senescence-resistant) mice in the midbrain thalamus and the hypothalamus. In addition, an IP administration of nicotine was found to improve learning ability of SAM-P/8 as shown by performance of a passive avoidance task. Nicotine may potentiate cognitive function in SAM-P/8. PMID- 7862737 TI - Spinal and supraspinal effects of pertussis toxin on opioid analgesia. AB - The effects of in vivo pertussis toxin (PTX) treatment on the functional effects of opioid agonists were examined in the mouse. Mice were injected intracerebroventricularly (ICV), or intrathecally (IT), or IT and ICV with PTX, and dose-response studies of the antinociceptive action of systemic (SC) morphine, fentanyl, and etorphine were conducted 10 days later. IT PTX decreased the potency (approximately 4.5-fold) of morphine more than ICV administration (approximately 1.5-fold), whereas the combination of IT and ICV administration produced an additive effect. When PTX was administered spinally and supraspinally, the potency of morphine, fentanyl, and etorphine was reduced similarly (approximately 5-7-fold), indicating that the effect of PTX does does not vary considerably among agonists of different intrinsic efficacies. These studies indicate that in vivo PTX can reduce the potency of opioid agonists with different intrinsic efficacies, and that spinal mechanisms appear to be more sensitive to PTX treatment. PMID- 7862738 TI - Stimulation of mouse brain gamma-hydroxybutyric acid transport by pyridoxal 5' phosphate. AB - A synaptosomal preparation from mouse brain transported gamma-hydroxybutyric acid in a manner displaying saturation kinetics. A Kt of 48 +/- 11 microM was calculated. In the presence of pyridoxal 5'-phosphate, uptake was markedly enhanced. Stimulation of uptake was observed with increasing concentrations of pyridoxal 5'-phosphate, up to a maximum of about 3.5 mM. Increasing concentrations above this value led to a steady decrease in the stimulation of uptake, till at 7 mM pyridoxal 5'-phosphate and above there was a noticeable inhibition of uptake. The presence of increasing concentrations of gamma hydroxybutyric acid gradually reduced the amount of stimulation, thus pyridoxal 5'-phosphate appeared to be producing its effect by reducing the Kt of the transport system rather than increasing its Vmax. PMID- 7862739 TI - Changes in mouse hippocampal EEG characteristics after oral administration of Ro 41-3696, nitrazepam, or zopiclone alone and in combination with ethanol. AB - Ro 41-3696, a benzoquinolizinone derivative, is a partial agonist to the benzodiazepine (BDZ) receptor and is expected to be a nonsedative hypnotic. The present comparative study was performed to examine the effects of the oral administration of Ro 41-3696, nitrazepam or zopiclone alone and in combination with a 'social' dose of ethanol on mouse hippocampal EEG. Ro 41-3696 (1-10 mg/kg), nitrazepam (0.1 and 1 mg/kg), and zopiclone (1 and 10 mg/kg) each alone caused an increase in the drowsy EEG pattern associated with a decrease in the duration of hippocampal rhythmic slow-wave activity (RSA). On the other hand, nitrazepam markedly lowered, while Ro 41-3696 and zopiclone slightly lowered the RSA frequency during waking mobility. In combination with a noneffective oral dose (1 g/kg) of ethanol, the reductions in both total duration and peak frequency of RSA caused by nitrazepam, unlike those by Ro 41-3696 and zopiclone, were significantly potentiated. In addition, only nitrazepam produced motor impairment. These results suggest that Ro 41-3696 acts more selectively than nitrazepam to promote the drowsy EEG pattern, and the partial agonistic properties may minimize the residual effects during waking mobility similar to the short-acting agent zopiclone. PMID- 7862740 TI - Effects of vinconate and pentobarbital against postischemic alterations in spirodecanone binding sites in the gerbil brain. AB - We investigated the effects of vinconate and pentobarbital against the alterations in spirodecanone binding in the gerbil striatum and hippocampus 5 h and 7 days after 10 min of cerebral ischemia, using receptor autoradiography. Vinconate and pentobarbital were given intraperitoneally 10 and 30 min prior to ischemic insult, respectively. The spirodecanone binding in vehicle-treated gerbils subjected to ischemia was unchanged in the brain 5 h after recirculation, compared with that in sham-operated animals. Seven days after ischemia, a significant elevation in the spirodecanone binding was observed in the striatum and the stratum radiatum of the hippocampal CA1 sector and the hippocampal CA3 sector of the vehicle-treated animals. Other regions showed no significant change in the binding. Vinconate and pentobarbital showed no significant change in the striatum and hippocampus 5 h after ischemia. However, the administration of vinconate inhibited a significant elevation in the spirodecanone binding in the lateral striatum and the stratum radiatum of hippocampal CA1 sector 7 days after ischemia. Pentobarbital also prevented a significant elevation only in the lateral striatum. A histological study revealed that cerebral ischemia caused severe neuronal damage in the lateral striatum and hippocampal CA1 and CA3 sectors. However, ischemic neuronal damage was not observed in the dentate gyrus. An immunohistochemical study also showed that numerous reactive astrocytes were evident in the hippocampus, particularly in the hippocampal CA1 sector, 7 days after ischemia. The present study demonstrates that cerebral ischemia can cause a conspicuous elevation in spirodecanone binding in the striatum and hippocampus. They also suggest that the postischemic elevation in the spirodecanone binding is partly prevented by treatment with vinconate and pentobarbital. These results suggest that the postischemic elevation in spirodecanone binding sites may reflect expression of reactive astrocytes. PMID- 7862741 TI - Effect of anesthetic and convulsant barbiturates on N-methyl-D-aspartate receptor mediated calcium flux in brain membrane vesicles. AB - The effects of anesthetic and convulsant barbiturates on brain N-methyl-D aspartate (NMDA) receptor function were examined in a cell-free membrane vesicle preparation from mouse hippocampus. Increases in intracellular free calcium concentrations (Cai) were determined using a fluorescent dye, Indo-1, after stimulation with the NMDA receptor agonist, L-glutamate. Anesthetic barbiturates inhibited NMDA responses in a concentration-dependent manner with a rank order of potency of secobarbital > amobarbital > pentobarbital > mephobarbital = phenobarbital >> barbital. However, the IC50 values for these barbiturates were larger than probable blood anesthetic concentrations. Barbiturates with both anesthetic and convulsant effects in mice [optical isomers of pentobarbital and secobarbital, 5-(2-cyclohexylideneethyl)-5-ethylbarbituric acid and (+/-) dimethylbutylbarbituric acid] also reduced NMDA responses. Inhibition of NMDA responses by racemic pentobarbital or isomers of pentobarbital was noncompetitive. Resting Cai was altered by all barbiturates tested except secobarbital and barbital, but not in a consistent manner, suggesting that the effect of barbiturates on resting Cai is not related either to their effects on NMDA receptor responses or to their behavioral effects. These results show that anesthetic and convulsant barbiturates inhibit NMDA responses, but their anesthetic and convulsant activities may be primarily due to their effects on other brain targets. PMID- 7862742 TI - Pharmacodynamic and pharmacokinetic interactions between alpha-methylparatyrosine and phenobarbitone. AB - The hypnosis and hypothermia induced by phenobarbitone (100 mg/kg i.p.) were greatly potentiated by combined treatment with alpha-methylparatyrosine (alpha MPT, 250 mg/kg i.p.). alpha-MPT per se produced sedation and hypothermia. Measurement of blood and brain levels of phenobarbitone in rats treated with phenobarbitone alone or phenobarbitone plus alpha-MPT revealed that the latter delayed the disappearance rates of phenobarbitone from both brain and plasma. These results suggest an interaction at the site of distribution, metabolism and/or excretion of phenobarbitone. The possibility of a pharmacodynamic interaction involving neurotransmitters is also discussed. PMID- 7862743 TI - Suppressive effects of eugenol and ginger oil on arthritic rats. AB - This study examined the effect of eugenol and ginger oil on severe chronic adjuvant arthritis in rats. Severe arthritis was induced in the right knee and right paw of male Sprague-Dawley rats by injecting 0.05 ml of a fine suspension of dead Mycobacterium tuberculosis bacilli in liquid paraffin (5 mg/ml). Eugenol (33 mg/kg) and ginger oil (33 mg/kg), given orally for 26 days, caused a significant suppression of both paw and joint swelling. These findings suggest that eugenol and ginger oil have potent antiinflammatory and/or antirheumatic properties. PMID- 7862744 TI - Endothelin ETA receptor antagonist reduces myocardial infarction induced by coronary artery occlusion and reperfusion in the rat. AB - The effect of the endothelin ETA receptor antagonist FR 139317 on myocardial infarction was studied in the rat. Under anesthesia, rats were subjected to 30 min of left main coronary artery occlusion and 3 h of reperfusion. FR 139317 (15, 35 and 70 mg/kg total dose) was continuously infused i.v. starting approximately 30 min before coronary artery occlusion and continuing throughout occlusion and reperfusion. The area at risk (AAR), determined using phthalocyanine dye, was in the range of 48-63% of the left ventricle (LV). The infarct zone (IZ) was evaluated by tetrazolium staining defect and its size was calculated as a percent of AAR. The IZ/AAR (%) was significantly reduced in rats treated with FR 139137 (15 mg/kg: 20 +/- 4%, n = 6; 35 mg/kg: 24 +/- 2%, n = 6, and 70 mg/kg: 26 +/- 4%, n = 8) compared to the vehicle group (36 +/- 2%, n = 22) (p < 0.05). When rats were treated beginning just prior to reperfusion, FR 139317 (35 mg/kg) also produced a significant reduction in infarct size (IZ/AAR: 22 +/- 1% for FR 139317, n = 6 vs. 39 +/- 6% for vehicle, n = 6, p < 0.05). These data suggest an important role for the ETA receptor-mediated effects of ET in the pathophysiology of myocardial infarction. ETA receptor antagonism may provide a novel therapeutic approach for cardioprotection in myocardial infarction. PMID- 7862745 TI - Vitamin E or probucol as donors for oxidation of human low-density lipoprotein by peroxidases/H2O2. AB - Horseradish peroxidase or myeloperoxidase and H2O2 oxidize human low-density lipoprotein (LDL) in the presence or absence of a xenobiotic donor without an essential lag phase as revealed by an increase in the absorption at 234 nm. In the latter case, natural antioxidants like vitamin E and congeners serve as donor; radical formation by the action of peroxidase has been described before. Otherwise trolox C or probucol have donor function in this system. After oxidation by peroxidase/H2O2 LDL showed the expected reduced antioxidant capacity against vitamin-E-consuming radicals. PMID- 7862746 TI - Effects of bisphosphonate derivatives on macrophage function. AB - The effects of three bisphosphonates (BPs), designated 4-amino-1 hydroxybutylidene-1, 1-bisphosphonate (AHBuBP), 6-amino-1-hydroxylidene-1, 1 bisphosphonate (AHHexBP) and chloromethylenebisphosphonate (Cl2MBP), were evaluated on the basis of their effect on the phagocytic activity, lysosomal enzyme release and superoxide anion production in the rat peritoneal macrophage (M phi). AHBuBP was found to inhibit in a concentration-dependent manner the phagocytosis of sheep red blood cells (SRBC). The same activity was seen with the phagocytosis of latex beads, although this effect was independent of calcium concentration. Conversely, AHHexBP and Cl2MBP were weak inhibitors of phagocytosis of both SRBC and latex beads. Inhibition studies on the phorbol myristate acetate-stimulated production of superoxide anion have shown all three BPs to be active. When compared with Cl2MBP, AHBuBP and AHHexBP were shown to be substantially active in inhibiting the release of beta-glucuronidase from ionophore A23187-stimulated rat peritoneal M phi. PMID- 7862747 TI - Phonetics of intervocalic consonant perception: retrospect and prospect. AB - This article reviews the production characteristics and perceptual cues of intervocalic consonants as a background for acoustic studies of consonant perception in fluent speech. Data show that in conversation intervocalic consonants occur much more commonly than consonants in initial or final position; all phonetic features are strongly represented. Production characteristics of intervocalic consonants are seen to depend on the tempo and rhythmic conditions of the syllables of which they are components. At a moderate tempo, consonants in syllable-final position combine with the onset consonant of the following syllable. This affects durational characteristics and may be explained by higher energy efficiency of CV units in production. Phonological phenomena are related to the shifts in syllable position and the temporal compensations of intervocalic consonant production. Studies of consonant perception in fluent context have dealt with tempo of utterance, position in word, and rhythmic pattern, as well as phonemic context. Major phenomena are effects of coarticulation, invariance in consonant perception, and cue interaction and masking. Much evidence suggests a dominance of the perceptual cues in the CV portion of VCCV and VCV sequences. We suggest that exploration of perception variables that affect consonants in fluent context would be expedited by reorienting experimental procedures to employ listener adjustment of stimuli, instead of the traditional phoneme identification and discrimination procedures with large sets of constant stimuli. Most of the relevant literature deals with stop consonants. Lateral, rhotic, and nasal consonants also deserve intensive study because of their very frequent occurrence. Theoretical issues of phoneme perceptual invariance and motor vs. auditory theory of perception are discussed in relation to proposed experiments which vary syllable tempo and stress pattern. PMID- 7862748 TI - Effects of speaking rate changes on native and nonnative speech production. AB - Twenty monolingual English speakers and 40 native Spanish speakers, who were either relatively proficient or nonproficient in English, produced English /p/ at self-selected normal and fast speaking rates. The native English (NE) subjects showed much the same rate effect on voice onset time (VOT) seen in earlier studies. Native Spanish (NS) subjects who were relatively proficient in pronouncing English used fewer short-lag stops and showed an English-like rate effect on VOT. NS subjects who were relatively nonproficient in English, on the other hand, used more short-lag stops and did not show a significant speaking rate effect on VOT, although they did demonstrate speaking rate effects on vowel duration and phrase duration. Among the NS subjects were 21 whose VOT values closely matched those of the NE subjects at both speaking rates, and who showed a rate effect similar to that found for the NE subjects. Their ability to modify VOT across speaking rates suggested that these NS subjects may have established a phonetic category for English /p/. PMID- 7862749 TI - Physiologists at US medical schools: education, current status, and trends in diversity. PMID- 7862750 TI - Friend-raising for biomedical research. PMID- 7862751 TI - [90th annual meeting of the Japanese Society of Psychiatry and Neurology. May 25 27, 1994. Matsuyama City. Abstracts]. PMID- 7862752 TI - [Unemployment and health]. AB - Reviews of the literature on the relationship between unemployment and psychological and physical health point clearly to the fact, that loss of employment has a negative influence on the state of health of the unemployed and increases the signs of pathology. The negative influence of unemployment on health is seen mainly among the long-term unemployed, for young people who cannot find a job after finishing their education and for their family members. The range and extent of the negative consequences are various. They depend on socio demographic, personality, situation and time factors and on the existing social support systems. A number of theoretical concepts (eg. of stress, life events, inability to fulfil latent psychological functions, the role of social structures etc.) are used to explain the mechanisms of the negative psychophysiological changes, connected with unemployment. However, it is possible, that the main role is played by an interaction of various factors, which influence the development of social and health related pathology. This indicates the necessity of creating detailed and varied programmes for prophylactics and treatment, based on scientific research. This is particularly important in Poland. Here the percentage of unemployment is very high. Unfortunately neither the Community, nor the political and administrative organs (including the Health Service) are equipped to cope with this new problem. To this must be added the lack of sufficient research, and inadequate knowledge about how unemployment spreads and about its consequences. PMID- 7862753 TI - [Symptom check-lists in the diagnosis and epidemiology of neurotic disorders]. AB - Epidemiological studies related to the occurrence of neurotic disorders commonly use symptom check-lists. The results of such studies depend on, amongst others, the construction of the questionnaire and especially on the specification of the value of the questionnaire (GSI) which is determined as the boundary between the "psychophysiological" or organic symptoms and neurotic symptoms. A control study was carried out on the norms of two symptom checklists which have been used for many years in Poland: SCL-"S" (73 symptoms), most often diagnosed in neurotic patients, at the time of constructing the questionnaire and the SCL-"O" (the same 73 + 62 other symptoms). The criterion population was made up of 843 untreated subjects and 2026 patients of day-hospitals. The norms specified by the method of finding the "optimal cut-off point" were approx. 5% in the SCL-"S" and 3% in the SCL-"O" higher for the cohort of women than for men. According to those norms, about 30% of the untreated population gains the same result of Global Severity Index (GSI) as about 90% of patients treated for neurotic disorders and could be diagnosed as neurotic disorders. The GSI norms for the SCL-"S" more often indicated the existence of these disorders in the group of untreated women than in the men's group, while the norms of SCL-"O" indicate a similar frequency of the disease independently of the gender. The symptom frequency analysis presenting differences in the women (1165 ss.) and men (861 ss.) patient groups and lead also to the hypothesis on the dependency of such epidemiological data on the construction of the symptom check-lists--especially the number of variables concerning symptoms more frequent in the female and/or in the male populations. PMID- 7862754 TI - [Acute non-allergic reaction after administration of penicillin as a factor in the occurrence of neurotic symptoms]. AB - The effect of a acute non-allergic reaction occurring after injection of procaine penicillin on the occurrence of different neurotic symptoms is a subject of the paper. 31 clinical cases, in which during the penicillin treatment the said reaction took place, were analysed. It has been found that the most often found consequence of that treatment is conversive neurosis, and subsequently the hypochondriac syndrome. On an average an acute non-allergic reaction occurred after the sixth injection. In 94% of the patients the neurotic symptoms appeared immediately after the described reaction. A positive correlation between the patient's age and an intensity of the converse symptoms was found. The Hoigne'a syndrome was a strong mental trauma, and was treated as an allergic shock for all of the patients. The patients were afraid of the next injection and they all refused to give permission for the continuation of such treatment. Neurotic syndromes related to Hoigne's syndrome turned out to be prolonged with a tendency for relapses, and low susceptibility to different methods of treatment. The mechanism of non-allergic acute reaction after procaine penicillin and ways of its prevention are also discussed. PMID- 7862755 TI - [Characteristics of personality structure and neurotic disturbances in patients with primary arterial hypertension]. AB - The aim of this study was to measure the prevalence of neuroses in an examined group of patients and to determine specific personality profiles in the group of men and women with primary arterial hypertension with or without coexisting neurosis. Data were collected from a group of 93 out-patients with primary arterial hypertension of the I and II degree according to WHO (51 men, mean age 47.9 years and 42 women, mean age 44.4 years). All subjects had secondary or university education. Neurotic disturbances were determined by the symptom check list (version "S") and estimation of the personality structure was performed by the Cattell 16 Personality Factors test. The prevalence of neurotic syndromes was 33% in men and 45% in women. We have found a higher frequency of neuroses than in the population, in both men and women with primary arterial hypertension, who have had secondary education. Factor F- (desurgency) was dominant in the male group (p < 0.01) and factors: A+, I+, O+, Q4+, B-, C-, E-, F-, N-, Q1- were predominant in the female group. The subjects with primary arterial hypertension, but without neurosis were characterised by the following personality factors: men by A+, B+, F- Q2- and women by A+ and I+. Moreover affectothymia (A+) was more frequent in men than in women. The personality structure of men with primary arterial hypertension and concomitant neurosis was characterised by the following 16 PF test factors: C- (low ego strength) and O+ (to be apprehensive/guilt proneness). Neurotic personality structure in women was described by the following 16 PF test factors: B- (less intelligent), C- (low ego strength), E- (submissiveness), F- (desurgency, sober), N- (artlessness, simple-minded), O+ (apprehensive/guilt-proneness) and Q4+ (high ergic tension). It is important, that the 16 PF test profile was different, both in hypertensive men and women and both with or without the presence of neurotic syndromes. This fact and the prevalence of neurosis among hypertensives should be taken into consideration in the psychologic approach and contemporary treatment of primary arterial hypertension. PMID- 7862756 TI - [Analysis of psychological data and social functioning in alcoholics]. AB - 74 male alcoholics participated in a three years prospective study. We have analysed data that patients obtained after the detoxification and 1, 2 and 3 years after discharge. Patients were divided into groups according to drinking behaviour. The psychological assessment included the MPI-Eysenck Personality Questionnaire, Q-sort self-esteem scale, Benton test and the WAIS. Social functioning was classified with reference to the Scale of Social Functioning. Our results indicate that the majority of patients presented disturbances in self esteem and an increased level of neuroticism. These psychological parameters were not connected with a drinking or sober outcome. Our data suggest that the cognitive impairment in alcoholics is relatively constant and does not improve despite sustained abstinence. In the whole group social functioning was disturbed after a period of drinking and was significantly improved together with the duration of abstinence. PMID- 7862757 TI - [Behaviors connected with emotions in supporting psychotherapy of chronic neurological patients]. AB - The examination of 8 behaviors connected with emotions during supporting psychotherapy of 75 chronic neurological patients was performed. We estimated correlations between examined behaviors. We maintain, that sympathy expressed to the psychotherapist is a stimulating factor and has a positive influence on the patient's mood. On the basis of functional analysis of the obtained correlations we established the main mechanisms of behaviors in the examined group. PMID- 7862758 TI - [Group psychotherapy of neuroses and personality disorders in regular soldiers]. AB - Environmental conditions cause neuroses and symptoms of personality disorders in regular soldiers. Military service in highly formalized and hierarchical conditions makes it impossible to: express emotions (particularly negative ones), to arrange one's own time, to choose the position and place of work. Another important psychotraumatic factor is excessive load of work and responsibility for the sake of "the service". Psychotherapy is the main part of neurotic and personality disorder therapy in regular soldiers. The social context is the bass for theoretical assumptions of psychotherapy carried out by the authors. Based on the theory of learning, the aims of the applied psychotherapy are: eagerness for the elimination of symptoms and changing the mode of behaviour. Group psychotherapy is carried out in stationary conditions, in groups of 8 to 13 patients, for 8-9 weeks. The applied methods are: debating psychotherapy, interaction-communicative methods, psychodrawing, musicotherapy, choreotherapy and relaxation techniques. As the result of the therapy, about 89% of symptomatic improvement and about 81% of the change of attitude and behaviour were obtained. PMID- 7862759 TI - [Hypnosis: alert or non-alert]. AB - The article includes a review of literature and own studies about hypnosis considered from the point of view of the subject's alertness or non-alertness, his activity or passivity in the hypnotic state. Activity is considered as a construct describing behavioral and experiential dynamics. This includes the general reactivity and the level of spontaneousness and initiative. The author's studies refer to the influence of hypnotic behavior on the dimension alert-non alert. The following factors were found to be important subject's preconception of hypnosis, the kind of hypnotic procedure used, subject's hypnotic susceptibility, subject's personality traits, implicite demand characteristics of particular suggestions, specific explicit suggestions and subject's training. PMID- 7862760 TI - [Neurotrophic growth factors in Alzheimer's disease]. AB - In recent years disturbances in releasing neurotrophic growth factors have been viewed as one of the causes of the development of Alzheimer's disease. It is assumed that abnormalities concerning neurotrophic growth factors (e.g. disturbances in releasing them and (or a wrong response of nerve cells to released growth factors) may be co-responsible for the development of abnormal functions of recent memory or concentration. It is assumed that their role in neurodegenerative processes consists primarily of increasing the survival rate of nerve cells and exerting an effect on the transmitting functions of CNS neurons. Attempts made at present to use growth factors in A.D. with a view to increasing the survival rate of degenerating nerve cells and improving the transmitting functions of neurons will be continued in future in pace with the advancement of our knowledge of their mechanisms. PMID- 7862761 TI - [Risk factors for dementia of the Alzheimer's type]. AB - A case-control study was conducted on 16 cases of probable Alzheimer's disease and 32 controls matched for age. The first control group was younger while the second was at the same age as patients with dementia of the Alzheimer's type. The patients were diagnosed according to DSM IIIR criteria. Information was obtained on birth and childhood, medical and surgical history, exposure to various social, psychological and biological factors as well as a family history of dementia. A structured questionnaire based on the AMDP--system was completed. Some of the variables studied reached statistical significance. First of all the sum of unfavourable environmental factors taking place during the person's childhood and elderly was predictive. Also head trauma was more frequent in patients with dementia. The findings suggest a possible etiologic role for some environmental factors in dementia of the Alzheimer's type. PMID- 7862762 TI - [Amyloid plaque in selected neurodegenerative disorders of the central nervous system]. AB - In this paper a review of the most recent investigations of the pathology of amyloid and of amyloid plaque is presented. The purpose of this report is to describe various clinical conditions (including their etiopathology and clinical manifestations) in which amyloid deposits (especially amyloid plaques) are significant features of the disease. Similarly, to define the neuropathological picture of amyloid deposits, molecular composition of amyloid fibrils and the genes which encode them. PMID- 7862763 TI - [Speech and thought disorder in frontal syndrome following subarachnoid hemorrhage]. AB - Here is described a case of a patient suffering from cerebral hemorrhage resulting in the perforation of the third cerebral ventricle and massive damage of the frontal lobes in consequence of the rupture of an intracranial aneurysm. After neurosurgical operation the patient's general state improved, but in spite of this he displayed symptoms of the frontal syndrome with many symptoms in the area of abstractional thinking and reflectiveness and a significant reduction of higher emotionality. Very interesting in this case is the neurolinguistic symptomatology. The rehabilitation and pharmacotherapy was very successful. This case is very interesting because it contains many of the symptoms called "frontal syndrome". It is also important to show the role of the frontal lobes in the integral process of mental life and in the role of the left hemisphere in the gnostic and coordinative processes of speech and other higher functions of the central nervous system. PMID- 7862764 TI - Special issue: Bruno Bettelheim's contribution to psychoanalysis. PMID- 7862765 TI - Bruno Bettelheim's contribution to psychoanalysis. Introduction. PMID- 7862766 TI - Bruno Bettelheim's unrecognized contribution to psychoanalytic thought. PMID- 7862767 TI - Bruno Bettelheim: the mysterious other. Historical reflections on the treatment of childhood psychosis. PMID- 7862768 TI - Bruno Bettelheim's contribution to our understanding of child abuse. PMID- 7862769 TI - Freud and man's soul: its significance to psychoanalysis. PMID- 7862770 TI - Bruno Bettelheim: culture in man, man in culture, and a language for both. PMID- 7862771 TI - Bettelheim among the folklorists. PMID- 7862772 TI - Reevaluating Bruno Bettelheim's work on the Nazi concentration camps: the limits of his psychoanalytic approach. PMID- 7862773 TI - Bettelheim on education. PMID- 7862774 TI - Enchantment and disenchantment with Bruno Bettelheim: a review of six works. PMID- 7862775 TI - Meditation and college students' self-actualization and rated stress. AB - This paper concerns the efficacy of meditation and relaxation in promoting self actualization and changes in self-reported stress among 62 college students. Two groups were given mantra meditation and a yogic relaxation technique referred to as Shavasana. Pre- and posttest measures were taken on the Personal Orientation Inventory and the Behavioral Relaxation Scale. Both groups showed significant increases in scores on self-actualization; however, no differences were found between groups. Meditation training was associated with larger gains in scores on measures of systematic relaxed behavior than of the relaxation training. PMID- 7862777 TI - Prevalence of prior adult sexual contact in a sample of adolescent male sex offenders. AB - The present study provides data on the prevalence of prior adult sexual contact among a sample of 47 adolescent male sex offenders and 109 male nonoffenders. Offenders (61.7%) reported a higher rate of sexual touching by an adult than did nonoffenders (19.3%). PMID- 7862776 TI - A confluent model of outcomes for adult children of alcoholics: implications for assessment, treatment, and research. AB - Current conceptions of adult children of alcoholics do not account for recent suggestions that characteristics used to describe them are not valid. These conceptions do not explain the documented heterogeneity with regard to life and therapeutic outcomes. In this paper, an alternative model of outcomes is formulated. This model is based on self-schema theory, behavioral self-regulation and self-efficacy, the influences of the "ecological environment," and objective signs and subjective symptoms of dysfunction. It is argued that the model provides a better "fit" to the empirical data concerning outcomes and carries implications for assessment, treatment, and research. PMID- 7862778 TI - Determinants of intentions of Junior High School students to become sexually active and use condoms: implications for reduction and prevention of AIDS risk. AB - The purpose of this study was to examine factors associated with young adolescents' increased risk for AIDS. A multiethnic sample of 303 seventh-grade students in three schools in the greater New York area completed questionnaires assessing their basic demographic characteristics (gender and ethnicity), AIDS knowledge, substance use (cigarette smoking, alcohol use), and decision-making skills. AIDS knowledge, substance use, decision-making skills, gender, and ethnicity predicted intentions to engage in sexual behavior in the future. Relevant knowledge of AIDS was associated with lower intentions to engage in sexual behavior in the future. More frequent substance use, less frequent use of decision-making skills, and being male increased intentions to engage in sexual behavior in the future. Our findings are discussed in terms of their implications for education and prevention of adolescent sexual activity and AIDS-risk reduction. PMID- 7862779 TI - Predicting the suicide rate in Wales. PMID- 7862780 TI - The dynamics of managed mental health care. AB - Presented here is an exploration of the motivations involved in the development and application of managed mental health care to the private practice of outpatient psychotherapy. The interaction of management policy and psychotherapy is conceptualized in a dynamic model designed to provide insights into effective care policies. The model is described first, then the development of managed care, which appears defensive and is becoming symptomatic to the point of needing significant change. It is suggested that management policies providing choices of therapists and therapies will be the most effective in addressing ethical, fiscal, and psychological concerns of funders, consumers, and providers. PMID- 7862781 TI - Violent sexual fantasies and sexual behavior. PMID- 7862782 TI - Comments on a process for identifying stages of dementia in residents of nursing facilities. AB - This paper gives a description of how items of the Global Deterioration Scale's Brief Cognitive Rating Scale and Functional Assessment Staging can be verified by reviewing specific sections and items of the Minimum Data Set for Nursing Facility Resident Assessment and Care Screening which is completed annually and updated every three months or when significant changes in health occur. A likely outcome of such comparison is improved understanding of the cognitive and functional status of residents with dementia and other medical conditions. PMID- 7862783 TI - Loneliness and pet ownership among single women. AB - Relationships among loneliness, pet ownership, and attachment were studied in a sample of 148 adult female students, 59 pet owners and 89 nonowners. No significant differences were found on the loneliness reported by pet owners and nonowners. A two by two analysis of variance showed that women living entirely alone were significantly more lonely than those living with pets only, with both other people and pets, and with other people but without pets. No associations were found between loneliness and pet attachment. Also, no significant differences were found in loneliness or pet attachment scores between dog and cat owners; however, women living only with a dog were significantly more attached to the dog than those living with both a dog and other people. Conversely, women living only with a cat were significantly less attached to the cat than those living with both a cat and other people. These findings indicate that having a pet can help to diminish feelings of loneliness, particularly for women living alone, and compensate for the absence of human companionship. PMID- 7862784 TI - Assessment of depression: using the MMPI, Millon, and Millon-II. AB - The analysis examined how the MMPI, original Millon, and Millon-II may be used for the assessment of clinical and personality characteristics of depressed patients. High-point code-type analysis of data from 133 depressed inpatients yielded seven MMPI personality profiles (incapacitated-depressive, intropunitive depressive, caught psychopath, hysteroid-dysphoric, schizotypal-depressive, ruminative-depressive, and psychotic-depressive) and eight Millon personality profiles (avoidant-depressive, conforming-depressive, hostile-depressive, hysteroid-depressive, disenfranchised-depressive, guilty-depressive, passive aggressive-depressive, and anaclitic-depressive). These profiles reflect important similarities in the personalities of the tested depressed inpatients and differences among them as well. Our interpretive framework is speculative but offers a basis for clinical hypothesis generation. PMID- 7862785 TI - Using the Maslach Burnout Inventory to assess educators' burnout at a university in South Africa. AB - Use of the Maslach Burnout Inventory with 94 faculty members at the University of the Western Cape, South Africa is described. Analysis indicated that the inventory can be considered a reliable measure of burnout in this educational setting. Confirmatory factor analysis indicated that the factorial structure of the scale was similar to those previously reported for educational groups in North America. Multiple regression analysis also indicated the significant predictors of the components of burnout in the present study (role conflict, role ambiguity, participation in decision-making, and number of students) are similar to those previously identified. PMID- 7862786 TI - Reliability and concurrent validity of the level of care and utilization survey. AB - A level-of-care instrument was developed for individuals with severe mental illness. A random sample of 300 patients residing in two state hospitals and a state-operated nursing home was used to test the concurrent validity and reliability of the instrument. Analysis indicated excellent test-retest reliability, good split-half reliability, adequate internal consistency, and reasonable concurrent validity. Thus, the questionnaire may provide a base for clinicians and administrators responsible for designing programs and health-care systems of treatment in the least restrictive environment possible. PMID- 7862787 TI - Stressful events, work-family conflict, coping, psychological burnout, and well being among police officers. AB - This study examined a research model developed to understand work attitudes and emotional and physical well-being. Data were collected from 828 police officers (including 738 men and 62 women) using questionnaires completed anonymously. Five groups of predictor variables identified in previous research were considered: individual demographic and situational variables, stressful events, work-family conflict, coping responses, and psychological burnout components. Considerable support for the model was found. Work attitudes and psychological well-being were more strongly predicted than were physical health and lifestyle behaviors. PMID- 7862788 TI - A selected bibliography of literature on revenge. PMID- 7862789 TI - AIDS knowledge and attitudes towards homosexuals of black first-year university students: 1990-1992. AB - Using an anonymous structured questionnaire to obtain baseline data on knowledge and attitudes of first-year black university students about the Acquired Immunodeficiency Syndrome (AIDS) and their attitudes towards homosexuals during 1990, 1991, and 1992 (ns = 1902, 2113, and 1558), the following information was obtained. Students' knowledge of AIDS was inadequate and misconceptions about AIDS transmission prevalent as were prejudiced and exclusionary beliefs about people with AIDS. Little difference was evident on any of the scales over the three-year period. PMID- 7862790 TI - Ranking police stressors. AB - Police stressors were measured using Spielberger's Police Stress Survey with a sample of 103 police officers. Rankings of police stressors are discussed. PMID- 7862791 TI - Assessment of self-esteem and wellness in health promotion professionals. AB - When researchers tested 90 wellness professionals attending the National Wellness Conference using the Adult Form of Coopersmith's Self-esteem Inventory and TestWell, participants scored above the norm on self-esteem and over-all wellness and on the subscales of Sexuality and Emotional Awareness, Safety, and Emotional Management. In addition, TestWell, a revised wellness inventory, showed internal reliability (alpha) of .84. PMID- 7862792 TI - Social desirability and alexithymia. AB - We examined the influence of alexithymia on social desirability among 215 Japanese college students. Alexithymic-scoring students who showed a lack of communicating their feelings to other people were likely to indicate higher scores on hostility and lower scores on social desirability. The scores on hostility were negatively correlated with those on social desirability. Recent studies have shown that alexithymia is positively correlated not only with neurotic and psychotic conditions but also with neuroticism. Unfavorable expression of hostile feelings by alexithymic-scoring students may be related to their lower scores on social desirability. PMID- 7862793 TI - Lying as a factor in research on sexuality. AB - This study investigated whether lying was a factor in research on sexuality among 1902 black South African first-year students. Consenting students completed structured questionnaires comprising 3 subject areas of biographical/career, sexuality, and political violence, each followed by an attitude scale. Subjects were more comfortable and truthful while completing the biographical/career and sociopolitical violence scales than the sexuality scale. PMID- 7862794 TI - Chronicity of symptoms in combat veterans with PTSD treated by the VA mental health system. AB - Self-report questionnaire data, collected at two stages of treatment, are presented for a group of 40 combat veterans with PTSD treated within the VA mental health system. Patients completed the Beck Depression Inventory, Mississippi Scale, and Dissociative Experiences Scale prior to treatment at a PTSD outpatient clinic and at midtreatment follow-up. Patients' symptom reports at follow-up were not correlated with length of time in treatment. Further, results suggest that patients' self-reported symptoms on these measures do not show evidence of improvement after entry into the VA mental health system. Explanations for this apparent chronicity of symptoms are discussed. PMID- 7862795 TI - Can meta-analysis help determine whether rehabilitation medicine improves outcome? PMID- 7862796 TI - Performance by gender in a stop-smoking program combining hypnosis and aversion. AB - Increased rates of smoking initiation and smoking-related illness among women have narrowed the gender gap in smoking behavior. Past studies of performance by gender in prevention and treatment programs have reported reduced success with women and have suggested a need for stronger interventions having greater effects on both genders' smoking cessation. A field study of 93 male and 93 female CMHC outpatients examined the facilitation of smoking cessation by combining hypnosis and aversion treatments. After the 2-wk. program, 92% or 86 of the men and 90% or 84 of the women reported abstinence, and at 3-mo. follow-up, 86% or 80 of the men and 87% or 81 of the women reported continued abstinence. Although this field study in a clinical setting lacked rigorous measurement and experimental controls, the program suggested greater efficacy of smoking cessation by both sexes for combined hypnosis and aversion techniques. PMID- 7862797 TI - Gender and the risk of violent death in Canada. PMID- 7862798 TI - Outcomes of the Minnesota Smoking Prevention Program. AB - 1,320 seventh-graders from a large midwestern public school district participated in a 6-hr. session of the Minnesota Smoking Prevention Program. Responses from students of the four trained and three control junior high schools indicated that the Minnesota program did not prevent students from becoming new users but rather encouraged those who were regular users to quit. PMID- 7862799 TI - Repetition avoidance in responses to imaginary questions: the effect of respondents' belief in ESP. AB - 42 subjects were given the Myers-Briggs Type Indicator which demands checking either one of two response variants for each of 81 questions. Before, they had completed an imaginary questionnaire version, that is, checked 81 times either "a" or "b" without seeing any questions. Three main findings emerged. (1) Over all subjects, repetitions of the same response alternative were significantly avoided only in the imaginary version, indicating that item content in the Myers Briggs Type Indicator overrode response stereotypy. (2) On the imaginary version, repetition avoidance was significant for those subjects who said they believed in extrasensory perception (ESP) but not for nonbelievers, corroborating previous reports of an association between belief in ESP and repetition avoidance. (3) In comparison to nonbelievers, believers in ESP scored higher on the dimension "feeling" (as opposed to "thinking") of the Myers-Briggs Type Indicator. This result is in line with the assumption that belief in ESP is associated with a style of thinking more typical for the right hemisphere. PMID- 7862800 TI - The military participation rate and suicide rates in Austria, 1873-1913. PMID- 7862801 TI - A conceptual scheme for assessing evenhandedness and (counter) self-serving attributional biases in relation to depression. AB - Various hypotheses have been proposed concerning the attributional styles of depressive and nondepressive persons. Some hypotheses are compatible with others; some are mutually exclusive. In this paper we present a scheme for organizing these hypotheses. A method is offered for deciding which hypothesis best fits data from samples which are heterogeneous with regard to extent of depression. The concepts reviewed include "self-serving bias," "counter-self-serving bias," "evenhandedness," "depressive lower self-enhancement," "counter-defensive attribution," the "Abramson, et al. hypothesis" that depressed persons attribute events with bad outcomes more to internal, stable, and global causes than do nondepressed persons, and the "Seligman, et al. hypothesis" that depressed persons attribute events of good outcome less to these causes than do nondepressed persons. PMID- 7862802 TI - Correlation of scores on the Eysenck Personality Inventory with those on the Gordon Personal Profile and Inventory. AB - Correlations of scores on the Eysenck Personality Inventory with those on the Gordon Personal Profile (for 160 university undergraduates) and with the Gordon Personal Inventory (for 260 undergraduates) showed that Eysenck and Eysenck's Extraversion and Neuroticism bear reasonably close correspondence to Gordon's Sociability and Emotional Stability. PMID- 7862803 TI - Predicting smoking status by symptoms of depression for U.S. adolescents. AB - This study examined the predictive relationships between adolescents' smoking and symptoms of depression. A national sample of 6,900 adolescents, ages 14 to 18 years, were selected for analysis. Variables of interest included measures for smoking status and symptoms of depression. Odds ratio and adjusted odds ratio from logistic regression analyses indicated that more of the 885 smokers than of the 6,015 nonsmokers reported feelings of unhappiness, sadness, or depression, hopelessness about the future, and having trouble going to sleep. PMID- 7862804 TI - Profiling psychological distortion in alleged child molesters. AB - Sex offenders frequently show denial and distortion during forensic psychological evaluations, but research into assessment of rationalizations and cognitive distortions among sex offenders has been limited. We examined patterns of psychological distortion in 59 alleged child molesters. We compared fake-good and fake-bad orientations on the MMPI with psychological distortion on the Multiphasic Sex Inventory questionnaire which assesses various psychosexual characteristics among sex offenders. Analysis indicated that distortion on the Multiphasic Sex Inventory indices of minimization and exaggeration was significantly associated with response-bias on the MMPI. Cognitive-distortion indices were highly influenced by response-bias. Admitters differed from deniers on scales with items requiring admission or denial of offenses. Caution is warranted in clinical interpretation of the validity scales of this questionnaire, which are of limited utility for deniers. Subtle items on cognitive-distortion indices may be useful in assessment of those who deny and should be subjected to further research. PMID- 7862805 TI - Societal and parental influences on adolescent sexual behavior. AB - A study of 1551 high school students in four midwestern states showed that more girls than boys reported "some" or "a lot" of encouragement to abstain from having sex. More boys than girls reported societal pressure to become sexually active. The sources of encouragement for abstinence were mother, father, and teacher. The largest difference reported between boys and girls was for friends; more than twice as many girls as boys reported that friends encouraged abstinence. Virgin vs nonvirgin comparisons showed similar results, with mother and father chosen most frequently, but nonvirgins chose guest speaker instead of teacher for third place. Regarding important decision-making factors, both boys and girls selected own feelings, health, future, boy- or girlfriend, and parents' feelings. Girls considered parents' feelings more while boys rated boy- or girlfriends' feelings higher. It was concluded that society exerts a strong influence through the media, but parents have the strongest influence on adolescents' sexuality. PMID- 7862806 TI - Assessment of change in scores on personal control orientation and use of drugs and alcohol of adolescents who participate in a cognitively oriented pretreatment intervention. AB - The primary purpose of this study was to assess the effect of participation in a cognitively oriented, pretreatment intervention on the control orientation of substance-using behavior of 48 adolescents admitted to drug-free outpatient treatment. Subjects were randomly assigned to one of two treatment conditions and to one of two counselors. A comparison of changes in control orientation between groups was made after implementation of the intervention with the treated group and after both groups had participated in six counseling sessions. A 2-way multivariate analysis of covariance showed type of treatment was significant. Follow-up analyses indicated the treated group were significantly more internal than the control group at both posttest occasions. A one-tailed chi-squared test indicated no significant association in substance use for the groups. PMID- 7862807 TI - Responsibility for eldercare: a concern for organizations? AB - This study examined responsibility for eldercare among 1608 employees of a single organization. Only 90 employees (5.6%) indicated such responsibilities. Women and men were equally likely to have eldercare responsibilities. The small percentage of employees having eldercare responsibilities reflected the relatively young age of the sample. While not a large problem for employees at present, as they and their parents age the firm may find increasing future need for policies and programs in this area. PMID- 7862808 TI - Comparison of the Millon Adolescent Personality Inventory and the Suicide Ideation Questionnaire--Junior with an adolescent inpatient sample. AB - The current investigation was undertaken to assess the correlation of scores on the Millon Adolescent Personality Inventory and the Suicide Ideation Questionnaire--Junior. 9 adolescents (aged 15 to 17 years), on being admitted to an inpatient psychiatric facility, were given the two inventories. Of the 20 categories on the Millon, scores on 10 were significantly correlated with scores on suicide ideation. High suicide ideators tended to experience school-related problems, report poor self-concept, have poor family rapport, and be overly sensitive. Results were discussed in light of the importance of finding a subtle and commonly administered assessment tool that would be useful for those who work with adolescents at risk for suicide. PMID- 7862809 TI - Social integration and primary versus secondary murder. PMID- 7862810 TI - Factor analysis of the General Health Questionnaire. AB - We present the factor structure of the General Health Questionnaire-60 as derived from a population of 2115 Army soldiers. An eight-factor principal components analysis provided the most clinically relevant solution and explained 58.0% of the variance. We distinguished two types of depressive symptomatology, suggesting the questionnaire may be useful in differentiating shame-ridden dysphoria from anergic disinterest. PMID- 7862811 TI - Depression and suicidal preoccupation in high school and college students. PMID- 7862812 TI - Japanese high school and college students' responses to the Adolescent Reinforcement Survey Schedule. AB - Factor-analyzed correlations among items of the Japanese Adolescent Reinforcement Survey Schedule by Japanese high school students (N = 939) and college students (N = 500) were compared to investigate the changes in reinforcers between mid- and late adolescence, gender differences, and the specific groupings of reinforcers which suggest certain interventions for either or both groups of adolescents. The factor analysis yielded ten interpretable factors in both groups. These factors were similar and did not suggest a dramatic shift in reinforcers between mid- and late adolescence. Items related to heterosexual activities and antisocial behaviors were rated as more pleasurable by males and items related to interpersonal relationships and academic activities were rated as more pleasurable by females. Since both groups of students attach high reinforcement value to interpersonal interaction with peers and family members, interventions focusing on social skills development might be popular and well attended. PMID- 7862813 TI - Effects of salbutamol upon performance on an operant screen for antidepressants. AB - The beta adrenergic (beta) agonist salbutamol increased reinforcement rates and decreased response rates on a differential-reinforcement-of-low-rate (DRL) 72-S schedule. These changes in DRL 72-S schedule performance are also produced by most clinically used antidepressants. The effects of salbutamol on a DRL 72-S schedule were dose-dependently antagonized by the beta antagonist metoprolol, but not changed by the 5HT antagonist methysergide. Additionally, neither salbutamol nor the antagonism of salbutamol by metoprolol caused disruption of DRL 72-S schedule performance. These results indicate that stimulation of beta receptors, and not of 5HT receptors, mediates salbutamol antidepressant-like effects on a DRL 72-S schedule. PMID- 7862814 TI - Intra-accumbens infusion of quinpirole impairs sensorimotor gating of acoustic startle in rats. AB - Prepulse inhibition (PPI) of the startle reflex is reduced by systemic administration of dopamine (DA) agonists. Since PPI is impaired in patients with schizophrenia, the DA agonist-induced disruption of PPI in rats may be a useful model for studying the pathophysiology of impaired sensorimotor gating in schizophrenia. In the present study, we replicated the observation that PPI is disrupted by systemic administration of the D2 agonist quinpirole, but not by the D1 agonist SKF 38393. PPI caused by weak [1-5 dB(A)] or more intense [10 dB(A)] prepulses was also disrupted by quinpirole infusion into the nucleus accumbens (NAC). The effects of intraaccumbens quinpirole on PPI were blocked by pretreatment with the D2 antagonist haloperidol. These results support the notion that the reduction of PPI after systemic administration of DA agonists is mediated via stimulation of NAC D2 receptors. PMID- 7862815 TI - Activation of central ATP-sensitive potassium channels produces the antinociception and spinal noradrenaline turnover-enhancing effect in mice. AB - ICV cromakalim, a K+ channel opener, produced antinociception. This effect was completely antagonized by ICV glibenclamide, a selective adenosine triphosphate sensitive K+ channel (KATP channel) blocker. Furthermore, direct opening of central KATP channels by ICV cromakalim increased the spinal noradrenaline (NA) turnover. On the other hand, the antinociception induced by ICV morphine (mu opioid agonist), but not ICV U-50,488H (kappa opioid agonist) was markedly potentiated by cromakalim. These findings suggest that the opening of central KATP channels may elicit the antinociceptive effect and activate the descending NAergic pathway, and central KATP channels play an important role as a modulator of the antinociception induced by mu agonists but not kappa agonists. PMID- 7862816 TI - Dopamine D1 and D2 antagonists attenuate amphetamine-produced enhancement of responding for conditioned reward in rats. AB - It has been suggested that the dopamine D1 receptor may play an important role in reward. The present study was undertaken to investigate the roles of dopamine D1 and D2 receptor subtypes in responding for conditioned reward. This was done by examining the effects of the D1 antagonist SCH 23390 and the D2 antagonists pimozide and metoclopramide on amphetamine-produced enhancement of responding for conditioned reward. The procedure consisted of three distinct phases. During the pre-exposure phase the rats were exposed to an operant chamber containing two levers. One lever produced a lights-off stimulus (3 s) and the other a tone stimulus (3 s). This was followed by four conditioning sessions during which the levers were removed and the rats were exposed to pairings of the lights-off stimulus with food. This phase was followed by two test sessions during which the levers were present and the number of responses made on each was calculated as a ratio of the number of responses made during the pre-exposure phase. A group receiving the vehicle during the test sessions showed a greater ratio of responding for the lights-off stimulus than the tone stimulus, indicating that the lights-off stimulus had become a conditioned reward. Amphetamine (0.1, 1.0, 2.0 and 5.0 mg/kg, IP, 5 min prior to test) specifically enhanced responding on the lever producing conditioned reward. SCH 23390 (5.0 and 10.0 micrograms/kg, SC, 2 h before test) and pimozide (0.1 and 0.2 mg/kg, IP, 4 h before test) dose dependently shifted the peak in the amphetamine dose-response function to the right, indicating an attenuation of conditioned reward.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862817 TI - Intravenous benztropine and propranolol challenges in tardive akathisia. AB - We challenged five patients suffering from tardive akathisia (TA) with intravenous benztropine (2 mg), propranolol (1 mg) and placebo (saline) using a random, double-blind cross-over design to examine the effects of the drugs on the subjective, objective and global manifestations of neuroleptic-induced akathisia. Benztropine produced a marginally significant, and propranolol a significant improvement in the overall manifestations of the disorder. The patients demonstrated a considerable placebo effect and marked variation in their responses to the drugs. The implications of these findings for the pathophysiology of TA in relation to acute akathisia and tardive dyskinesia are discussed. PMID- 7862818 TI - Differential effects of excitotoxic lesions of the amygdala on cocaine-induced conditioned locomotion and conditioned place preference. AB - The reinforcing properties of cocaine can readily become associated with salient environmental stimuli that acquire secondary reinforcing properties. This type of classical conditioning is of considerable clinical relevance, as intense drug craving can be evoked by the presentation of stimuli previously associated with the effects of cocaine. Given the large body of evidence that implicates the amygdaloid complex in the learning of stimulus-reward associations, the present experiments examined the effects of quinolinic acid lesions of the amygdala on cocaine-induced conditional locomotion and conditioned place preference (CPP). Destruction of the amygdala did not affect basal or cocaine-induced locomotion, suggesting that the amygdala does not mediate the unconditioned psychomotor stimulant effects of this drug. Preconditioning lesions also failed to affect cocaine-induced conditional locomotion. Specifically, exposure of both lesioned and non-lesioned rats to a cocaine-paired environment produced significant conditional increases in locomotion. This lack of effect was contrasted by a complete blockade of cocaine-induced CPP by the amygdaloid lesions. These data demonstrate that cocaine-induced stimulus-reward conditioning can be differentially affected by lesions of the amygdala. PMID- 7862819 TI - Beta-adrenergic antagonists attenuate withdrawal anxiety in cocaine- and morphine dependent rats. AB - Rats were treated chronically with either cocaine (20 mg/kg/day, 14 days), morphine (incrementing doses of 10 mg/kg/day to 80 mg/kg, 11 days) or saline. During morphine or cocaine abstinence (48 h), dependent rats showed increased anxiety-like behavior in a conditioned defensive burying paradigm as evidenced by significantly shorter latencies to begin burying as well as a 4-fold increase in burying duration relative to saline-treated animals. This withdrawal-induced increase in burying behavior was blocked by pretreatment with either the beta adrenergic antagonist propranolol (5 mg/kg) or the lipophobic selective beta 1 antagonist, atenolol (5 mg/kg). These results are consistent with the possibility that activation of peripheral beta 1 receptors may substantially contribute to withdrawal-induced anxiety and that beta-adrenergic antagonists could be useful in treating in cocaine and morphine dependent addicts. PMID- 7862820 TI - Effects of oxazepam on anxiety: implications for Fowles' psychophysiological interpretation of Gray's model. AB - The present dose-response study investigated the effects of the benzodiazepine oxazepam (Serax) on anxiety as measured by autonomic and self-report indices in a nonclinical sample. Given Fowles' (1980, 1988) theory that electrodermal activity primarily reflects the activity of the behavioral inhibition system (BIS) while heart rate primarily reflects the activity of the behavioral activation system (BAS), we predicted that electrodermal indices of anxiety would be more affected by oxazepam than heart rate. Psychophysiological and self-report measures were recorded prior to and following a speech stressor in subjects given placebo (n = 17), 15 mg oxazepam (n = 19), and 30 mg oxazepam (n = 17). Anxiolytic effects were found during stressed state as measured by skin conductance level but not heart rate or self-reported anxiety. Furthermore, the anxiolytic effects of oxazepam were noted only during the stressful phases of the experiment. The results are viewed as supportive of Fowles' motivational interpretation of the distinction between heart rate and electrodermal responding. PMID- 7862821 TI - Subjective and cardiovascular effects of cocaethylene in humans. AB - Preclinical studies have shown cocaethylene (the ethyl ester of benzoylecgonine) to produce pharmacologic effects of similar magnitude to those of cocaine. These observations, however, cannot establish whether or not cocaethylene produces cocaine-like subjective effects. We report the results of experiments in which three healthy male, paid volunteers were intravenously injected with the water soluble fumarate salt of cocaethylene in escalating doses. Subjective effects and cardiovascular parameters were the dependent variables. The maximal dose of cocaethylene base administered (0.25 mg/kg) produced subjective effects that were judged as milder and tachycardic effects that were comparable to those produced by the intravenous injection of an equivalent dose (0.25 mg/kg) of cocaine base. PMID- 7862822 TI - Delta-opiod receptor-mediated forced swimming stress-induced antinociception in the formalin test. AB - Forced swimming stress-induced antinociception (FSSIA) was assessed using the formalin test. Male ICR mice, weighing about 30 g, were forced to swim in water at 20 degrees C for 3 min. In unstressed mice, SC injection of formalin (0.5%) to the hindpaw caused a biphasic response: an immediate nociceptive response (first phase) followed by a tonic response (second phase). Although forced swimming stress (FSS) had no effect on the duration of the first-phase response, FSS significantly reduced the duration of the second-phase response. The effect of FSSIA on the second-phase response was blocked by naltrindole (1 mg/kg, SC), a selective delta-opioid receptor antagonist, but not by beta-funaltrexamine (20 mg/kg, SC), a selective mu-opioid receptor antagonist. These results indicate that FSS may selectively reduce the second phase of the formalin-induced nociceptive response, primarily through delta-opioid receptors. PMID- 7862823 TI - Behavioral effects of dopaminergic agonists and antagonists alone and in combination in the squirrel monkey. AB - The effects on schedule-controlled operant behavior of the D2 receptor agonist, quinpirole, and the D1 agonist, SKF 38393, were assessed alone and in combination with selective dopamine-receptor antagonists. Squirrel monkeys (Saimiri sciureus) were trained to press a response key under fixed-interval and fixed-ratio schedules of food reinforcement. The fixed-interval schedule maintained relatively low rates of responding that increased up to food presentation. The fixed-ratio schedule maintained relatively constant high rates of responding. Quinpirole increased rates and disrupted the temporal pattern of responding under the fixed-interval schedule at doses (0.1-1.0 mg/kg) that decreased rates of responding under the fixed-ratio schedule. Under the fixed-interval schedule, the D2 antagonists, spiperone (0.003-0.006 mg/kg) and haloperidol (0.003-0.01 mg/kg), and the D1 antagonist, SCH 23390 (0.03 mg/kg), shifted the quinpirole dose-effect curve to the right. The maximal effects of quinpirole were decreased at the highest doses of the antagonists. However, only spiperone antagonized effects of quinpirole on the rates of responding under the fixed-ratio schedule. The D1 agonist, SKF 38393, dose-dependently (1.0-10.0 mg/kg) decreased rates of responding under both schedules. Those effects were not antagonised by any doses studied of either spiperone (0.003 mg/kg) or SCH 23390 (0.003-0.3 mg/kg). Rather, both antagonists enhanced the effects of SKF 38393.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862824 TI - Substitution of the 5-HT1 agonist trifluoromethylphenylpiperazine (TFMPP) for the discriminative stimulus effects of ethanol: effect of training dose. AB - The role of the ethanol training dose on the ability of the selective 5-HT1 agonist TFMPP (m-trifluoromethylphenylpiperazine) to produce ethanol-like discriminative stimulus effects was evaluated in three groups of rats trained to discriminate 1.0 g/kg (n = 5), 1.5 g/kg (n = 6) or 2.0 g/kg (n = 7) ethanol (IG) from water using a two-lever procedure with food reinforcement available under a fixed ratio 20 (FR 20) schedule. Ethanol generalization gradients were comparable in the three groups, indicating few potency differences in the ethanol stimulus across training dose. However, the ability of TFMPP (0.1-1.7 mg/kg; IP) to substitute for ethanol was dependent on the training dose. TFMPP resulted in partial substitution in the 1.0 g/kg group, complete substitution for 1.5 g/kg group and no substitution in the 2.0 g/kg ethanol training group. The results indicate a serotonergic component to the discriminative stimulus effects of an intermediate dose of ethanol that is not prominent as the dose of ethanol is raised. These data add further support for the hypothesis that ethanol produces a mixed discriminative cue, the components of which are not uniformly amplified when the dose of ethanol is increased. PMID- 7862825 TI - Conditioned place preference induced by microinjection of 8-OH-DPAT into the dorsal or median raphe nucleus. AB - Experiments were conducted to examine the ability of the selective 5 hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT) to induce a conditioned place preference following peripheral injection, and direct microinjection into the dorsal or median raphe nuclei. An unbiased place preference paradigm was used in which control animals showed no preference for either of two compartments differing in terms of colour (white versus black), floor texture (rough versus smooth) and olfactory cues (no odour versus acetic acid odour). Drug treatments were paired with access to either of the two compartments, and saline injections were paired with access to the other compartment. Rats experiencing a low dose of 8-OH-DPAT (125 micrograms/kg) with a specific compartment demonstrated a significant preference for that compartment over one paired with saline injections. The magnitude of this effect was similar to that observed in rats treated with 1.5 mg/kg d-amphetamine. A significant place preference was found in animals receiving injections of 8-OH-DPAT in the dorsal raphe at 0.1 microgram but not 1 microgram. Animals also displayed a preference for the compartment paired with 1 microgram 8-OH-DPAT injected into the median raphe; lower doses were not effective. These results indicate that the mechanism by which 8-OH-DPAT induces a conditioned place preference involves activation of raphe somatodendritic 5-HT1A autoreceptors, leading to a reduction in 5-HT neurotransmission. This demonstration of the rewarding properties of 8-OH DPAT, together with previous results showing increased feeding and sexual behaviour following 8-OH-DPAT treatment, strongly suggests an important role for brain 5-HT systems in reward and reinforcement processes. PMID- 7862826 TI - Psychophysiological interactions between smoking and stress coping? AB - Earlier studies with different types of stressors suggested that cigarette smoking might selectively dampen physiological stress reactions in passive rather than in active coping situations. This hypothesis was tested in the present study using the same task for both types of coping, but with two different instructions. Twenty-four female regular smokers were assigned either to a group requiring active coping or to a group requiring passive coping with ongoing electric shocks, and tested in two sessions where they performed a pre- and a postsmoking/non-smoking trial of the rapid information processing task (RIP). Smoking increased RIP task performance, cardiovascular and electrocortical arousal, and reduced anxiety throughout the session. Active coping, as compared to passive coping, produced greater increases in heart rate and blood pressure, a greater pre- to post-treatment decrease in reaction time and higher pain ratings of the electrical shocks. However, interactions between the effects of smoking and the type of coping were few and did not suggest a plausible concept. Thus, it was concluded that, although the typical effects of smoking as well as the differentiation between active and passive coping seen earlier with the same paradigm were confirmed, cigarette smoking did not affect the effects of the two coping conditions in a differential way. PMID- 7862827 TI - Behavioural evidence for "D-1-like" dopamine receptor subtypes in rat brain using the new isochroman agonist A 68930 and isoquinoline antagonist BW 737C. AB - The full efficacy, high potency isochroman D-1 agonist A 68930 demonstrated greater than 220-fold selectivity for D-1 over D-2 receptors. A 68930 (0.06 and 0.25 mg/kg) readily induced intense grooming, together with vacuous chewing; these responses became less evident following higher doses (1.0 and 4.0 mg/kg) and sniffing became prominent. Intense grooming was blocked by three D-1 antagonists, the benzazepines SCH 23390 (0.01-1.0 mg/kg) and NNC-756 (0.01-1.0 mg/kg), and the isoquinoline BW 737C (0.2-5.0 mg/kg); however, vacuous chewing was not antagonised by SCH 23390 and NNC-756, but was blocked by BW 737C. Intense grooming was attenuated by the D-2 antagonist YM 09151 (0.005-0.5 mg/kg) while vacuous chewing was enhanced. These data suggest that intense grooming is mediated by a "D-1 like" receptor that recognises all known chemical classes of D 1-selective compounds, while vacuous chewing may be mediated by a pharmacologically distinct subtype of "D-1-like" receptor that recognises preferentially the isochromans and isoquinolines. PMID- 7862828 TI - Reinforcing effect of the D1 dopamine agonist SKF 81297 in rhesus monkeys. AB - Rhesus monkeys with IV catheters were allowed to self-administer cocaine for 1 h/day. When responding was stable, saline or the D1 dopamine agonist SKF 81297 (SKF; 0.001-0.3 mg/kg/inj) was substituted for cocaine. At least two doses of SKF maintained responding above saline levels in all monkeys. The D1 antagonist SCH 39166 (0.001-0.03 mg/kg, IM) was then administered 30 min before sessions of self administration of the lowest dose of SKF that maintained behavior (0.01 mg/kg/inj). SKF-maintained responding decreased in a dose-related manner, suggesting antagonism of the reinforcing effect. These results suggest that stimulation of D1 receptors can initiate a reinforcing effect and further implicate D1 receptors in the reinforcing effects of drugs that increase dopamine neurotransmission. PMID- 7862829 TI - The tricyclic antidepressant clomipramine dose-dependently reduces regional cerebral metabolic rates for glucose in awake rats. AB - The time course and the relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male Fischer-344 rats after administration of clomipramine (CMI), a serotonin (5-HT) uptake inhibitor and clinical antidepressant. rCMRglc was determined, using the quantitative autoradiographic [14C]2-deoxyglucose technique, in 64 brain regions at 20, 40, 60, 120, and 180 min after administration of CMI 50 mg/kg IP and 120 min after CMI 2 and 10 mg/kg IP. The peak metabolic effect was observed at 120 min after CMI. At that time, CMI 2 and 10 mg/kg IP significantly reduced rCMRglc from control values in 12 (19%) and 14 (22%) brain regions, which correspond to areas with high densities of 5-HT reuptake sites (e.g. visual and limbic areas and raphe nuclei). CMI 50 mg/kg produced widespread rCMRglc reductions in 34 (53%) brain regions, including cortical, hippocampal, raphe and cerebellar areas. The topographic distribution and the relation to time and dose of CMI effects on rCMRglc are different from those of 5-HT1A [8-hydroxy-2(di-N-propylamino) tetralin], 5-HT1B-C (m-chlorophenylpiperazine) and 5-HT3 (quipazine) agonists and resemble those produced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), an agonist of 5-HT2 receptors, suggesting that CMI may prefentially stimulate this 5-HT receptor subtype. PMID- 7862830 TI - Effects of oral ethanol self-administration on the EEG of alcohol preferring and nonpreferring rats. AB - EEG measures have been shown to differ in human subjects who are at genetically increased risk for the development of alcoholism. In the present study, EEG was recorded in rats that were selectively bred for alcohol-preferring (P) and nonpreferring (NP) behaviors during an ethanol self-administration paradigm. In this paradigm, rats initially learned to press a lever for a 0.2% saccharin solution. Ethanol was then added to the saccharin solution in increasing concentrations while saccharin was faded progressively. EEG recordings were analyzed under three different conditions: baseline, 0.2% saccharin and 10% ethanol. Statistical analyses were carried out within each group of rats for three 10-min intervals in each condition. NP rats showed increases in EEG power in the 6-32 Hz frequency ranges 20-30 min following ethanol availability. In contrast, no significant EEG effects were found for P rats in the 10% ethanol condition with respect to time. EEG power in the three time periods (0-10, 10-20, 20-30 min) was also compared between conditions (baseline, saccharin, 10% ethanol). For NP rats, a significant increase in EEG power during the 20-30 min time interval was found in the 10% ethanol session for the 16-32 Hz frequency range as compared to baseline and saccharin. In P rats, a significant increase in the power of the EEG was found during the first 10 min in the 10% ethanol session in the 8-16 Hz frequency range as compared to baseline and saccharin. The two rat lines also differed in their behavioral responses to the self-administration paradigm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862831 TI - Effects of variation in chronic dose of cocaine on contingent tolerance as assessed in a milk-drinking task. AB - Tolerance to the suppressive effects of cocaine on milk drinking by rats was studied using a contingent tolerance experimental design. Three separate groups (n = 6) of rats received 8.0, 16.0, or 32.0 mg/kg cocaine daily 15 min before a 15-min period of access to sweetened condensed milk for 20 days. Three additional groups of six rats each received the same chronic doses 15 min after access to milk. Milk, water, and food intake as well as body weight were measured daily. Tolerance effects were assessed by comparing initial acute dose-effect determinations with a probe dose-effect redetermination in which all rats again received doses of cocaine pre-session after having experienced the differential pre- or post-session chronic treatment. Behavioral tolerance on the milk intake measure was observed for the 8.0 mg/kg and 16.0 mg/kg doses, but not for the 32.0 mg/kg chronic treatment, even though the latter group exhibited evidence of tolerance in the water intake measure. Chronic treatment with 8.0 and 16.0 mg/kg produced different outcomes in that chronic exposure to 16.0 mg/kg in the presence of milk resulted in generalization of tolerance to both a lower (8.0 mg/kg) and a higher dose (32.0 mg/kg), but the group receiving 8.0 mg/kg did not exhibit generalization of tolerance to higher doses. Modest sensitization effects were observed in the rats treated post-session with either 8.0 or 16.0 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862832 TI - Canine cataplexy is preferentially controlled by adrenergic mechanisms: evidence using monoamine selective uptake inhibitors and release enhancers. AB - Narcolepsy is currently treated with anti-depressants to control REM-related symptoms such as cataplexy and with amphetamine-like stimulants for the management of sleepiness. Both stimulant and antidepressant drugs presynaptically enhance monoaminergic transmission but both classes of compounds lack pharmacological specificity. In order to determine which monoamine is selectively involved in the therapeutic effect of these compounds, we examined the effects of selective monoamine uptake inhibitors and release enhancers on cataplexy using a canine model of the human disorder. A total of 14 compounds acting on the adrenergic (desipramine, nisoxetine, nortriptyline, tomoxetine, viloxazine), serotoninergic (fenfluramine, fluoxetine, indalpine, paroxetine, zimelidine) and dopaminergic (amfonelic acid, amineptine, bupropion, GBR 12909) systems were tested. Some additional compounds interesting clinically but with less pharmacological selectivity, i.e., cocaine, dextroamphetamine, methylphenidate, nomifensine and pemoline, were also included in the study. All compounds affecting noradrenergic transmission completely suppressed canine cataplexy at low doses in all dogs tested, whereas compounds which predominantly modified serotoninergic and dopaminergic transmission were either inactive or partially active at high doses. Our results demonstrate the preferential involvement of adrenergic systems in the control of cataplexy and, presumably, REM sleep atonia. Our findings also demonstrate that canine narcolepsy is a useful tool in assessing the pharmacological specificity of antidepressant drugs. PMID- 7862833 TI - Blood glucose and human memory. AB - As it has been suggested that blood glucose might play a role in the action of some cognitive enhancing drugs, the influence of glucose containing drinks on human memory was examined. In a double-blind study the influence was examined of a drink containing 50 g glucose, or a placebo, on the ability to recall a word list. There was a significant correlation between blood glucose values and the number of words recalled. Those whose blood glucose levels were increasing remembered significantly more words than those whose blood glucose levels were falling. No relationship was found between blood glucose and performance on a test of spatial memory. In a second study blood glucose levels were raised for 2 h by taking a series of glucose-containing drinks. The number of words recalled from a word list correlated significantly with blood glucose levels but not with recall of a Wechsler story. The glucose-induced improvement in memory did not occur only in those whose blood glucose levels were initially low; rather it occurred irrespective of initial blood glucose level. PMID- 7862834 TI - Effects of the beta-2 adrenergic agonist zinterol on DRL behavior and locomotor activity. AB - The purpose of the present study was to assess the behavioral effects of the beta adrenergic agonist zinterol and to determine whether its actions were mediated by beta adrenergic receptors. Zinterol reduced response rate and increased reinforcement rate of rats under a differential-reinforcement-of-low-rate schedule in a dose-dependent manner; significant decreases in response rate and increases in reinforcement rate were observed at doses of 0.1-1 mg/kg. The effect of 0.3 mg/kg zinterol on this behavior was blocked by pretreatment with the beta adrenergic antagonist propranolol. Zinterol also reduced locomotor activity in a dose-dependent manner; significant reductions were observed at doses of 0.3-10 mg/kg. Similarly, the effect of 1 mg/kg zinterol on locomotor activity was antagonized by propranolol. These effects of zinterol were similar to those of other beta adrenergic agonists as well as those of antidepressant drugs. Although the site of action (central versus peripheral) of zinterol was not determined in the present study, an experiment was carried out to determine if zinterol could act centrally after peripheral administration. The ability of repeated, systemic administration of zinterol to reduce the density of beta adrenergic receptors in cerebral cortex and cerebellum was determined. Repeated treatment with a high dose of zinterol (10 mg/kg, IP) reduced the density of beta adrenergic receptors in these brain regions, suggesting that, at least under certain conditions, systemically administered zinterol did have access to the central nervous system. PMID- 7862835 TI - Flexible effects of quantified cigarette-smoke delivery on EEG dimensional complexity. AB - A quantified smoke delivery system (QSDS) was used to experimentally control the administration of inhaled cigarette smoke to 28 male smokers. One puff (2 s, 35 cc) was taken every 30 s on a cigarette (nicotine yield 1.0 mg) until the char line reached 3 mm from the filter wrap. The smoke was inhaled for 5 s. Resting eyes-closed and eyes-open EEG was recorded from F3, F4, P3, and P4 before and after quantified smoke delivery (QSD). EEG dimensional complexity (DCx, a measure derived from chaos theory) was computed using the Takens-Ellner method. QSD appeared to have a 'flexible' effect on EEG DCx, primarily lowering it in subjects whose pre-smoking level was high, not affecting it in subjects whose pre smoking level was intermediate, and tending to raise it in subjects whose pre smoking level was low. This replicates previous results obtained with ad libitum smoking, suggesting the hypothesis that smoking may have an "optimizing" effect on the complexity of brain dynamics. PMID- 7862836 TI - Drug discrimination is a continuous rather than a quantal process following training on a VI-TO schedule of reinforcement. AB - Debate continues as to whether drug discrimination in animals is an inherently quantal or continuous process. This issue is important in determining the appropriate interpretation of results from drug discrimination studies designed to assess the nature of drug-induced interoceptive cues. The quantal approach holds that subjects perceive a drug cue in an all-or-none manner, while the continuous view proposes that when appropriate training and testing procedures are used, subjects can discriminate along a continuum of interoceptive cues. Data consistent with the quantal view have consistently been generated by animals trained to respond on schedules of reinforcement having an FR component. Since quantal responding is a characteristic of these schedules, results from drug discrimination studies using training schedules with FR components are of little value in empirically determining whether drug discrimination reflects a quantal or continuous process. Use of variable schedules of reinforcement might be more appropriate because the pattern of responding generated does not preclude results consistent with either of the competing views. Data from the following studies that trained subjects using VI schedules with a concurrent TO for incorrect lever responding were analyzed: Barrett et al. (1982): L-5-hydroxytryptophan versus saline; Smith (1990): diazepam versus pentylenetetrazol; Barrett et al. (1992): amphetamine versus haloperidol; Barrett and Steranka (1983): amphetamine versus haloperidol. In every case, when experimental conditions produced a group mean intermediate to that for the training drugs, the distribution of scores for individual animals was normally rather than bimodally distributed. PMID- 7862837 TI - Development of acute tolerance after oral doses of diazepam and flunitrazepam. AB - Flunitrazepam (1 and 2 mg), diazepam (10 and 20 mg) or placebo was administered to healthy, male volunteers, and the time course of psychomotor impairment, as indicated by simple and complex choice reaction time and movement time, was studied during a period of 6 h after drug intake. To examine whether acute tolerance developed, the observed performance during decreasing drug plasma concentration was compared to the predicted performance based on kinetic-dynamic modelling of the observed performance during the first 1.5 h after intake when the drug plasma concentrations were increasing or at peak level. Placebo corrections of the test scores were accomplished to adjust for diurnal variation and the possible influence of learning during the test day. After the flunitrazepam treatments, the predictions overestimated the actual performance significantly with respect to simple and choice reaction time at the 6-h session after intake. After the diazepam treatments, however, no significant deviation was detected between predicted and observed performance. The results indicate that acute tolerance develops with respect to impairment of attention demanding performance after medium to large doses of flunitrazepam, and that tolerance is expressed after approximately 4-6 h following intake. PMID- 7862838 TI - An acute effect of triazolam on muscarinic cholinergic receptor binding in the human brain measured by positron emission tomography. AB - An acute effect of triazolam, a potent benzodiazepine agonist, on cholinergic receptor binding in the human brain was measured by PET (positron emission tomography) using [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB), a potent muscarinic cholinergic receptor antagonist. Two PET scans were performed in each subject: (1) control scan; (2) after oral administration of 0.5 mg triazolam or placebo. The previously discussed amnestic effect of triazolam was measured by immediate and delayed recall of meaningful and meaningless syllables. A compartment model employing the radioactivity in the cerebellum as an input function was used for the quantification of receptor binding. The binding parameter, k3, was decreased after triazolam administration in all measured regions, whereas no change was observed after placebo treatment. The reduction compared to the control study varied from 8.6 +/- 3.7% in the temporal cortex to 16.3 +/- 6.3% in the thalamus. Triazolam administration impaired both immediate and delayed recall of syllables, whereas placebo administration had no effects. Benzodiazepine agonists are reported to decrease the cortical acetylcholine release. The decrease of acetylcholine release in the synaptic cleft might be the explanation for the decreased binding of [11C]NMPB. PMID- 7862839 TI - Reduction in ATP-sensitive potassium channel-mediated antinociception in diabetic mice. AB - To test our hypothesis that the abnormally low efficacy of mu-opioid agonists in diabetic mice may be due to functional changes in ATP-sensitive potassium channels, we evaluated the effects of cromakalim on the tail-flick latencies in diabetic and non-diabetic mice. Anti nociceptive effects of morphine (10 micrograms, ICV) in diabetic mice were significantly less than that in non diabetic mice. Morphine-induced antinociception in non-diabetic mice was antagonized by pretreatment with glibenclamide (30 micrograms, ICV), an ATP sensitive potassium channel blocker. Cromakalim (0.3 and 1 micrograms, ICV) produced significant, dose-dependent antinociception in non-diabetic mice, which was significantly reduced by pretreatment with glibenclamide. However, cromakalim did not markedly affect the tail-flick latencies in diabetic mice, even at higher doses (3 micrograms, ICV). On the other hand, [D-Pen2,5]enkephaline (DPDPE, 5 micrograms, ICV), a selective delta-opioid receptor agonist, produced significant antinociception in both diabetic and non-diabetic mice. Since pretreatment with glibenclamide significantly reduced the antinociceptive effect of DPDPE in non diabetic mice but not in diabetic mice, delta-opioid receptor-mediated antinociception in diabetic mice may be independent of potassium channels. These results suggest that dysfunction of ATP-sensitive potassium channels may contribute to the demonstrated poor antinociceptive response of diabetic mice to mu-opioid agonists. PMID- 7862840 TI - Serotonin-induced platelet intracellular calcium mobilization in depressed patients. AB - Serotonin(5-HT)-stimulated intracellular calcium(Ca) mobilization was measured in the platelets of depressed patients to assess 5-HT2 receptor function. The 5-HT induced Ca response was significantly higher in unmedicated patients with bipolar depression and melancholic major depression than in those with non-melancholic major depression and normal controls. The enhanced Ca response to 5-HT failed to correlate with severity of depressive symptoms. In patients with bipolar disorder and melancholic major depression, there was no significant difference in 5-HT stimulated Ca response between the unmedicated group and those in remission. These results suggest that 5-HT2 receptor function is increased in some types of depression, and raise the possibility that the enhanced Ca response to 5-HT may be trait dependent rather than state dependent. PMID- 7862841 TI - A comparison of the effects of the D1 receptor antagonists SCH 23390 and SCH 39166 on suppression of feeding behavior by the D1 agonist SKF38393. AB - The hypophagic effect of the D1 receptor agonist SKF 38393 is not dose dependently antagonized by the D1 antagonist SCH 23390. Moreover, the receptor specificity of this interaction remains in question, since SCH 23390 has significant activity at both 5-HT2 and 5-HT1C receptors, and SKF 38393 also interacts with 5-HT1C receptors. To determine the relative significance of these actions, a comparison was made between the anorectic effects in rats of SCH 23390 (0.1-1.0 mg/kg) and the benzonaphthazepine SCH 39166 (0.1-3.0 mg/kg), a D1 antagonist with negligible affinity for 5-HT sites. Both compounds inhibited food intake dose-dependently, with SCH 23390 being approximately twice as potent as SCH 39166. Behaviorally inactive and active doses of both antagonists were tested in combination with the D1 agonist SKF 38393 (10-56 mg/kg). Neither antagonist was able to produce more than a marginal attenuation of the agonist-induced hypophagia. This demonstrates that previous failures to reverse the behavioral actions of SKF 38393 by SCH 23390 were not due to specific actions of this particular antagonist. Finally, like SCH 23390, SCH 39166 (0.3 mg/kg) was able to attenuate fully the anorectic effects of the D1 agonist SKF 82958 (1.0 and 3.0 mg/kg), demonstrating that neither compound is intrinsically unable to block D1 receptor-mediated hypophagia. The results demonstrate the generality of the D1 antagonist-mediated effect on feeding and call into question the use of SKF 38393 as a D1 agonist in studies of feeding, and perhaps in other contexts as well. PMID- 7862842 TI - Flumazenil exerts intrinsic activity on sleep EEG and nocturnal hormone secretion in normal controls. AB - The physiological function of benzodiazepine (BDZ) receptors includes regulation of sleep and neuroendocrine activity. Most of the pharmacological effects of BDZ are blocked by flumazenil. However, recent neurological and behavioral studies suggest that flumazenil has its own central intrinsic activity. This issue was addressed in a study of the sleep EEG and the nocturnal secretion of growth hormone and cortisol in ten normal male controls, who were given flumazenil either alone or in combination with the BDZ agonist midazolam, placebo and midazolam alone. Flumazenil prompted an increase in sleep onset latency, a decrease in slow wave sleep and an increase in wakefulness. Plasma cortisol concentrations after flumazenil administration were lower than after midazolam. Both flumazenil and midazolam decreased nocturnal growth hormone secretion. After simultaneous application of both BDZ receptor ligands the growth hormone blunting was amplified. Our study demonstrates that at the level of the sleep EEG and neuroendocrine activity flumazenil is capable of exerting both agonistic and inverse agonistic or antagonistic effects. PMID- 7862843 TI - Using a computer model to explore impairments of acquisition processes following ingestion of diazepam. AB - Hypotheses about the information processes impaired in diazepam-induced amnesia were tested by fitting the output from a computer simulation of list learning to observed serial position curves and to overt rehearsal protocols. Twenty-four subjects received an average weight-relative dosage of 0.18 mg/kg oral diazepam; 24 subjects received placebo. Immediate free recall of 16-word lists was examined at 2- and 8-s presentation times. Subjects receiving diazepam recalled significantly fewer words than placebo subjects (diazepam = 6.77 +/- 2.39 words; placebo = 9.29 +/- 1.42 words); their memory impairment was greater at the 8-s than 2-s presentation time. Tests of nonlinear regression models based on computer simulations of list learning performance were consistent with the hypothesis that diazepam reduces rehearsal capacity and disrupts the formation or utilization of contextual and inter-item associations. Among these causes of diazepam-induced amnesia, the disruption of contextual associations appears most important. The results further suggest that quantitative modeling of memory data may complement traditional methods of inferring relationships between brain processes and cognitive dysfunction in amnesic states. PMID- 7862844 TI - Effects of alcohol pretreatment on human marijuana self-administration. AB - Alcohol and marijuana are frequently used together, yet there has been little study of how the presence of one drug might affect consumption of the other. The present study examined the effects of alcohol pretreatments on marijuana self administration in a group of 15 males and 5 females who were users of both drugs. During evening sessions in a recreational setting, pairs of subjects consumed drinks containing 0.0, 0.3 or 0.6 g/kg alcohol 30 min before a 60-min period of ad libitum marijuana smoking. Marijuana self-administration was assessed in several ways: by measuring the number of cigarettes smoked, the increase in expired air carbon monoxide resulting from marijuana smoke inhalation, and the increase in heart rate due to THC absorption. None of these variables was significantly affected by the alcohol pretreatments, although substantial individual differences were observed. These results indicate that low to moderate doses of alcohol do not systematically influence marijuana self-administration. PMID- 7862845 TI - Discriminative stimulus properties of the benzodiazepine receptor inverse agonist methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). AB - The purpose of this study was to determine whether rats could be trained to discriminate the stimulus properties of the benzodiazepine (BZ) receptor inverse agonist DMCM from saline in a conditioned taste aversion paradigm. On a drug trial, water-deprived rats were injected with DMCM (0.55-0.6 mg/kg IP), allowed access to a 0.25% saccharin solution for 30 min, and then injected with LiCl. On non-drug trials, saline injections bracketed the drinking period. Conditioned controls were treated similarly with DMCM and saline on drug and non-drug trials, but received injections of saline instead of LiCl. At the completion of training, CMCM produced a 69% reduction of saccharin consumption on drug trials, compared with 23% for conditioned controls. The stimulus properties of DMCM were then measured by its ability to reduce the preference for saccharin over water in a two-bottle choice test. DMCM reduced saccharin preference in rats that received discrimination training from 68% to 19%, but did not alter saccharin preference in conditioned controls. Other compounds with varying activity at BZ receptors were evaluated for their ability to substitute for the discriminative stimulus effects of DMCM. Two BZ receptor inverse agonists, beta-CCE (10-18 mg/kg) and FG 7142 (3.2-18 mg/kg), substituted completely for DMCM. Partial substitution for DMCM was shown by the BZ receptor antagonist CGS 8216 (3.2-10 mg/kg) and the non BZ convulsant pentylenetetrazol (10-20 mg/kg). The BZ receptor agonists chlordiazepoxide (0.32-5.0 mg/kg), diazepam (0.32-10 mg/kg), and alprazolam (0.1 3.2 mg/kg) and the BZ receptor antagonist flumazenil (1.0-32 mg/kg) failed to substitute for the DMCM stimulus. Pretreatment with flumazenil (1.0 mg/kg) blocked the stimulus effects of the training dose of DMCM and produced a shift to the right of the DMCM generalization curve. The pattern of compounds that substituted for the DMCM stimulus and the blockade of that stimulus by flumazenil indicate that the stimulus properties of DMCM are associated with its effects as a BZ receptor inverse agonist. PMID- 7862846 TI - A comparison of the effects of the novel muscarinic receptor agonists L-689,660 and AF102B in tests of reference and working memory. AB - Four experiments compared the CNS effects of a novel M1/M3 receptor agonist L 689,660 with those of the M1/M3 muscarinic receptor agonist AF102B. In the mouse tail-flick test of antinociception (TF) the minimum effective doses to increase tail-flick latency (MED) of L-689,660 and AF102B were 0.03 mg/kg and 10.0 mg/kg, respectively. In a rat conditioned-suppression-of-drinking (CSD) test of reference memory, doses of 0.3 and 1.0 mg/kg L-689,660 and a dose of 5.0 mg/kg AF102B reversed a scopolamine-induced deficit in performance (0.6 mg/kg). Although there was a tendency for L-689,660 to reverse the scopolamine-induced (0.4 mg/kg) performance deficit in a rat delayed-matching-to-position (DMTP) test, the difference failed to reach statistical significance. In contrast, a 5.0 mg/kg dose of AF102B potentiated the scopolamine-induced deficit in choice accuracy and the number of trials completed on this task. In a response sensitivity (RS) test, chain-pulling rates were significantly decreased by L 689,660 (MED = 0.03 mg/kg) and by AF102B (MED = 5.0 mg/kg). These results suggest that L-689,660 and AF102B may ameliorate or reverse a scopolamine-induced deficit, but only at doses that also reduce chain-pulling rates on operant schedules of reinforcement. PMID- 7862847 TI - An examination of the behavioural specificity of hypophagia induced by 5-HT1B, 5 HT1C and 5-HT2 receptor agonists using the post-prandial satiety sequence in rats. AB - Previous studies have shown that administration of 5-HT1B, 5-HT1C or 5-HT2 agonists decreases food intake in rats. However, it has not been established whether these drugs induce satiety or decrease feeding by a non-specific mechanism. In the present study the post-prandial satiety sequence was used to characterise the actions of the 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane (DOI), the 5-HT1B/5-HT1C receptor agonists, 1-(3 chorophenyl) piperazine (mCPP) and 1-[3-(trifluoromethyl)phenyl] piperazine (TFMPP), and the 5-HT1B agonist, 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)H indole (RU 24969), on feeding in rats. All four compounds reduced food intake in rats that had been food deprived overnight. The 5-HT1B/5-HT1C agonists, TFMPP (at a dose of 1.0 mg/kg) and mCPP (at a dose of 3.0 mg/kg), appeared to produce satiety as their effects on the satiety sequence were similar to those induced by a food pre-load. In contrast, the 5-HT1B agonist RU 24969 and the 5-HT2 agonist DOI did not produce behavioural profiles that resembled satiety. Thus, RU 24969 elevated active behaviours and did not accelerate resting whereas DOI appeared to induce hypophagia by a non-specific fragmentation of behaviour. The results suggest that simultaneous activation of 5-HT1B and 5-HT1C receptors may be sufficient to elicit behaviourally specific satiety in the rat. In contrast, selective activation of 5-HT2 receptors does not induce satiety but elicits active behaviours and decreases feeding by response competition. PMID- 7862848 TI - Effects of the calcium antagonist isradipine on cocaine intravenous self administration in rats. AB - The effect of isradipine, a dihydropyridine calcium antagonist, on cocaine intravenous self-administration in rats was investigated. Administration of (+/ )isradipine (1.25-5 mg/kg SC) 2 h before the cocaine self-administration session induced a significant and dose-dependent increase in the number of cocaine injections with respect to basal values. This effect was stereospecific, with the (+) form of isradipine being active, while the (-) stereoisomer was ineffective. These results suggest that isradipine antagonizes the rewarding properties of cocaine, possibly by inhibiting those dopaminergic systems related to reward mechanisms. These results further indicate a possible use of isradipine, or structurally similar compounds, in the treatment of cocaine related disorders. PMID- 7862849 TI - Factors influencing the reinforcing and subjective effects of ephedrine in humans. AB - There has been little study of the abuse liability of ephedrine, a naturally occurring drug used in medicine for thousands of years and currently sold as a "legal" stimulant. The present study measured the reinforcing and subjective effects of ephedrine in a group of 27 adults (18 females and 9 males) with no history of drug dependence. A discrete-trial choice procedure was used to assess the reinforcing effects of a single oral dose of ephedrine selected to produce a moderate subjective response in each subject (range: 37.5-75 mg). A number of variables (gender, current and past drug use, personality, and baseline mood and arousal) were examined in an attempt to identify sources of variability in response to ephedrine. Of the 27 subjects, 5 chose ephedrine on either 2 or 3 out of a possible 3 occasions; overall, ephedrine was chosen on 17% of occasions. In the group as a whole, ephedrine had no effect on ratings of drug liking, but did increase ratings of "high" and scores on the MBG ("euphoria") scale of the Addiction Research Center Inventory. Ephedrine also increased scores on a number of mood scales reflecting CNS stimulation and anxiety. Ephedrine choice was positively associated with current use of marijuana and lower levels of baseline anxiety and hunger, as well as with lower scores on two scales measuring dimensions of the personality trait of harm avoidance. Males and females differed in their response to ephedrine--males chose ephedrine more frequently than females and showed a more positive mood response to the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862850 TI - A mouse model of early social interactions after prenatal drug exposure: a genetic investigation. AB - The aim of the present study was to (i) characterise the mouse behavioural profile (particularly social interactions) during the preweaning period, (ii) assess the effects of prenatal exposure to an anticonvulsant drug widely used in clinical practice, (iii) examine possible genetic differences both in baseline behavioural profiles and in sensitivity to drug-induced effects. Following a balanced intra-strain fostering procedure, the offspring of C57BL/6J and CBA inbred mouse strains from mothers exposed during pregnancy to either phenobarbitone (PHB, 60 mg/kg) or vehicle (VEH) given intraperitoneally (IP) during days 10-16 of gestation, were observed for early social interactions in the home cage during the last part of the preweaning period (days 20 and 21). The behavioural repertoires of the two strains differed markedly, in that C57 pups were more involved in Play soliciting, Locomotor-rotational play, and in Maintenance activities, while CBA mice spent much more time being inactive or exploring the environment. C57 and CBA mice also differed in the sensitivity to PHB exposure. On the whole, time spent in Investigative/Affiliative behaviours was increased, while the frequency of Play soliciting patterns was reduced in PHB treated mice. The treatment of the fostering mother had only negligible effects, suggesting that PHB-induced changes in behaviour were largely due to direct effects of the substance on the foetus. These results indicate that specific items of the preweaning behavioural profile, and particularly social interactions, are influenced by early PHB exposure, and that the responses are heavily affected by the genotype. PMID- 7862851 TI - Discriminative stimulus effects of alpidem, a new imidazopyridine anxiolytic. AB - Alpidem in an imidazopyridine derivative which binds selectively to the omega 1 (BZ1) receptor subtype. It is active in some, but not all, behavioural tests sensitive to benzodiazepine anxiolytics and has clinical anti-anxiety effects. However, in a previous study, it was shown that alpidem did not substitute for chlordiazepoxide in rats trained to discriminate this benzodiazepine. The present experiments were carried out to investigate the discriminative stimulus properties of alpidem in greater detail. In the first experiment rats learned to discriminate a dose of 10 mg/kg alpidem from saline. Acquisition of the discrimination was long and performance unstable. Chlordiazepoxide, clorazepate and zolpidem substituted only partially for alpidem but the effects of the training dose of alpidem were blocked by 10 mg/kg flumazenil. The second experiment established stimulus control more rapidly to a dose of 30 mg/kg alpidem. Alpidem induced dose-related stimulus control, and dose-related and complete substitution for alpidem was produced by zolpidem, abecarnil, CL 218,872, triazolam and suriclone. Partial substitution occurred with chlordiazepoxide, clorazepate and pentobarbital. In most cases, high levels of substitution were produced only by doses which greatly reduced response rates even though the training dose of alpidem produced only modest decreases in rates. Ethanol, buspirone and bretazenil produced very little substitution for alpidem and both flumazenil and bretazenil antagonised the effects of alpidem. In two further experiments alpidem was found to substitute for the stimulus produced by zolpidem (2 mg/kg) but not for that produced by ethanol (1.5 g/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862852 TI - Nimodipine and haloperidol attenuate behavioural sensitization to cocaine but only nimodipine blocks the establishment of conditioned locomotion induced by cocaine. AB - The classical conditioning of the behavioural effects of cocaine has been shown to contribute to behavioural sensitization. In the present experiments, it was demonstrated that the effects of cocaine in rats can be conditioned to contextual stimuli. Furthermore, sensitization to cocaine's locomotor effects were demonstrated, and shown to be context specific. Nimodipine (10 mg/kg, SC), an L type dihydropyridine Ca2+ channel antagonist, appeared to completely block the establishment of conditioning of cocaine's effects, but only partially blocked sensitization to cocaine. Haloperidol (0.05 mg/kg, IP), a relatively specific D2 dopamine receptor antagonist, attenuated behavioral sensitization but had no influence on the establishment of the conditioned component of cocaine. These results indicate that the sensitization to, and the development of classical conditioning of, cocaine's behavioural effects can be pharmacologically dissociated, but that a non-associative process involved in sensitization is normally overridden by conditioning factors. PMID- 7862853 TI - Influence of caffeine on information processing stages in well rested and fatigued subjects. AB - The effects of caffeine on different information processing stages were examined by using choice reaction time tasks. Independent variables were stimulus degradation, stimulus-response compatibility, time-uncertainty, state of the subject, and caffeine treatment. The task variables were assumed to affect the following processing stages; encoding, response selection and motor preparation, respectively. A 200 mg dose at the beginning of the experiment and a maintenance dose of 50 mg caffeine or lactose half-way through the session were administered to well rested and fatigued subjects, double-blind and deceptively. Behavioural measurements, event-related potentials (ERPs) and mood questionnaires were used to assess caffeine effects. The data showed that caffeine shortened reaction time. This effect showed an interaction with stimulus degradation and time uncertainty. In addition, ERP results supported the view that caffeine increases cortical arousal and perceptual sensitivity. Stimulating effects of caffeine were mainly located at input and output stages of the information processing system. Central processes were unaffected by caffeine. Fatigued subjects showed larger improvements in performance after caffeine than well-rested subjects. The results also indicated that caffeine effects were not stimulating in all subjects: 6 out of 30 subjects did not show arousing effects of caffeine. PMID- 7862854 TI - Aversive properties of the kappa opioid agonist U50,488 in the week-old rat pup. AB - mu Opioids have been shown to produce analgesia and to be reinforcing during the first week of life in the rat. kappa Opioids also have analgesic actions in both the infant and adult, but can be aversive in the mature animal. We examined the aversive effects of the kappa opioid agonist U50,488 during the first postnatal week in the rat pup in three ways. In the first experiment, U50,488, injected peripherally (1.0-30.0 mg/kg), was paired with an odor and pups were tested 8 h later for positional preference for avoidance of that odor. This task is similar to conditioned preference/aversion tests used with adult animals. Both 3- and 7 day-old pups learned to avoid the odor adulterated side at the two higher doses. When exposed to odors previously associated with U50,488, pups at both ages decreased locomotor activity. In a second experiment, acute treatment with U50,488 increased ultrasonic distress vocalizations (USV) equally at 3 and 7 days of age, increased locomotor activity, and decreased rectal temperature. Neither of the latter two effects was correlated with the increase in USV production. The third experiment showed that conditioned odor cues increased USV 8 h later in 3- and 7-day-old pups at 1.0-10.0 mg/kg without changes in activity or rectal temperature. The results from these studies suggest that U50,488 can produce aversions in the neonatal rat pup as it does in the adult. PMID- 7862855 TI - Cross-tolerance studies of serotonin receptors involved in behavioral effects of LSD in rats. AB - Like hallucinogenic 5-HT2 agonists, LSD (d-lysergic acid diethylamide) produces characteristic decreases in locomotor activity and investigatory behaviors of rats tested in a novel environment. Because LSD is an agonist at both 5-HT1A and 5-HT2 receptors, however, the respective influences of these different receptors in the behavioral effects of LSD remain unclear. In particular, the paucity of selective 5-HT1A antagonists has made it difficult to assess the specific contribution of 5-HT1A receptors to the effects of LSD. An alternative approach to the delineation of receptor-specific effects is the use of cross-tolerance regimens. In the present studies, rats were pretreated with saline, 8-hydroxy 2(di-n-propylamino)-tetralin (8-OH-DPAT) (0.5 mg/kg SC), 1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane (DOI) (1.0 mg/kg SC), or LSD (60 micrograms/kg SC), every 12 h for 5 or 8 days. Thirty-six hours later, rats were tested in a behavioral pattern monitor 10 min after injection of saline, 0.5 mg/kg 8-OH-DPAT, 1.0 mg/kg DOI, or 60 micrograms/kg LSD. As expected, tolerance to the decreases in locomotor activity produced by acute administrations of 8-OH-DPAT, DOI, or LSD occurred when rats were pretreated chronically with 8-OH-DPAT, DOI, or LSD, respectively. Furthermore, pretreatment with either 8-OH-DPAT or DOI produced cross-tolerance to LSD. These results support the hypothesis that the effects of LSD in this model reflect a combination of 5-HT1A and 5-HT2 effects and support the view that there is an interaction between 5-HT1A and 5-HT2 receptors. PMID- 7862856 TI - Subjective and cardiovascular responses to nicotine combined with caffeine during rest and casual activity. AB - Although nicotine and caffeine have separately been shown to acutely increase subjective arousal, their combined effects are unclear. Furthermore, their effects during casual physical activity, the condition under which individuals usually experience nicotine and caffeine, are unknown. Smokers who were regular coffee drinkers (n = 19, 9 males, 10 females) participated in eight morning sessions, involving nicotine/placebo, caffeine/no caffeine, and rest/physical activity (i.e. 2 x 2 x 2 within-subjects design). Nicotine (15 micrograms/kg) or placebo was given via measured-dose nasal spray intermittently after consumption of decaf coffee with or without added caffeine (5 mg/kg), followed by subjective [Profile of Mood States (POMS), Stress-Arousal Checklist, visual analog scales] and cardiovascular (heart rate, blood pressure) measures. Casual physical activity was standardized by low-intensity bicycle riding while sitting comfortably. Results indicated significant subjective and cardiovascular effects of nicotine and caffeine individually, with the combination of nicotine and caffeine generally producing additive or greater than additive effects for each measure. However, activity mediated some of the subjective effects of nicotine, as nicotine appeared to be "stimulating" during rest but not during activity. There were no differences between males and females. These findings suggest that nicotine per se and caffeine generally have additive subjective and cardiovascular effects, and that nicotine may influence subjective stimulation differentially depending on whether a smoker is resting or engaged in casual activity. PMID- 7862857 TI - Nicotine-induced place preferences following prior nicotine exposure in rats. AB - The motivational properties of morphine and nicotine were investigated in an automated conditioned place preference (CPP) procedure using a two-compartment apparatus. The accuracy of the photocell recording system was assessed by correlation with direct observation. In a counterbalanced conditioning design, graded doses of morphine (0.1-3.2 mg/kg SC) produced dose-related CPP. Under similar conditions, a dose of nicotine (0.6 mg/kg SC) previously reported to produce CPP failed to show an effect. Increasing the number of conditioning trials from 4 to 12 did not facilitate CPP with nicotine. After pretreatment with nicotine (0.4 mg/kg SC) daily for 7 days prior to conditioning, nicotine (0.4-0.8 mg/kg) produced increasing magnitudes of CPP. Locomotor activity was assessed during both conditioning and extinction tests. During conditioning, nicotine but not morphine decreased activity in the first conditioning trial, but by the fourth trial, marked stimulation was apparent following administration of either drug. Activity in the drug-paired compartment was not increased during tests for CPP carried out in the undrugged state following 4 conditioning trials with either morphine or nicotine, but there was evidence for conditioned hyperactivity after 12 conditioning trials with nicotine. The results suggest that motivational properties of nicotine can be detected in counterbalanced CPP procedures, but only in subjects with a history of nicotine exposure. The CPP produced by morphine or nicotine does not appear to be an artefact associated with conditioned changes in locomotor activity. PMID- 7862858 TI - Potentiation of the ambulation-increasing effect induced by combined administration of MK-801 with ethanol in mice. AB - Although both MK-801 (dizocilpine: 0.1 mg/kg, IP) and ethanol (1.6 nd 2.4 g/kg, PO) only slightly increased ambulatory activity in mice, their combination produced a marked enhancement of the ambulation-increasing effect. The combination of MK-801 (0.03 mg/kg) with ethanol (1.6 and 2.4 g/kg) also elicited a significant increase in the mouse's ambulation. A significant enhancement of the effect was produced by the combination of ketamine (3 and 10 mg/kg) with ethanol only (2.4 g/kg). The ambulation increment induced by the combination of MK-801 (0.1 mg/kg) plus ethanol (1.6 g/kg) was dose-dependently inhibited by YM 09151-2 (0.0001-0.01 mg/kg IP), SCH 23390 (0.001-1 mg/kg IP), reserpine (0.1-1 mg/kg, IP) and ceruletide (0.00001-0.001 mg/kg, IP), and the highest dose of each drug was effective for complete inhibition of the ambulation. Naloxone (0.05-5 mg/kg IP), apomorphine (0.001-0.1 mg/kg IP) and alpha-methyl-p-tyrosine (50-200 mg/kg, IP) partially reduced the ambulatory activity induced by the combination of MK-801 with ethanol. These results suggest that the dopaminergic system, particularly via presynaptic changes in the release of stored dopamine, as well as the opioid system, are involved in the interaction of MK-801 with ethanol. PMID- 7862859 TI - Pharmacological analysis of the rate-decreasing effects of mu and kappa opioids in pigeons. AB - The present study investigated the rate-decreasing effects of several mu (morphine and l-methadone) and kappa (bremazocine, U69,593 and U50,488) opioid agonists in pigeons. Mu and kappa agonists were examined alone, in combination with naltrexone or the mu-selective opioid antagonist, beta-funaltrexamine (beta FNA), and in pigeons treated chronically with U50,488. Naltrexone was equipotent in shifting the morphine, l-methadone and bremazocine dose-effect curves to the right, but was less potent in shifting the U69,593 dose-effect curve and did not shift the U50,488 dose-effect curve. Beta-FNA shifted the l-methadone dose-effect curve to the right but did not shift the bremazocine, U69,593 or U50,488 dose effect curves. Pigeons that developed tolerance to U50,488 following daily administration were cross-tolerant to bremazocine but not to l-methadone. Taken together, these experiments indicate that the rate-decreasing effects of morphine and l-methadone are mediated by mu opioid receptors, whereas the rate-decreasing effects of bremazocine, U69,593 and U50,488 in pigeons differ depending on the pharmacological procedures used to assess their effects. PMID- 7862860 TI - Acute and chronic treatment with 5-HT reuptake inhibitors differentially modulate emotional responses in anxiety models in rodents. AB - This study investigated behavioural effects of very potent 5-HT reuptake inhibitors after acute treatment (cianopramine and citalopram), as well as after chronic treatment (cianopramine), in two behavioural models of anxiety: 1) the light/dark choice procedure in mice and 2) the elevated plus-maze test in rats. In addition, the responses of mice to novelty in a free exploration paradigm were assessed after acute administration of both drugs. A single injection of cianopramine or citalopram increased neophobic reactions in the free exploration test. Furthermore, these drugs increased the avoidance reaction to a brightly illuminated chamber in the light/dark choice procedure as well as to open arms in the elevated plus-maze test. In contrast, after chronic treatment (10 mg/kg IP, once daily for 21 days) of cianopramine, anxiogenic-like effects were no longer produced in the light/dark choice paradigm whereas in the elevated plus-maze test, anxiolytic-like effects appeared. These results shed more light on the 5-HT hypothesis of anxiety, insofar as the increased availability of 5-HT resulting here from reuptake inhibition seems to initially result in an increased emotional reactivity which, however, subsequently disappears during chronic treatment. PMID- 7862861 TI - Diphenylhydantoin potentiates the EEG and behavioural effects induced by N-methyl D-aspartate antagonists in rats. AB - The N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors are involved in the electrical and behavioural generalization of epileptiform activity within the brain. In rats, both competitive and non-competitive NMDA antagonists induce three dose-dependent stages of EEG patterns: 1) increase in cortical desynchronization periods; 2) increase in amplitude of cortical high frequency (20-30 Hz), low voltage (30-50 microV) background activity; 3) appearance of cortical slow (2-3 Hz) wave-sharp wave complexes. These EEG changes are accompanied by stimulatory-depressive behavioural effects such as stereotypy (circling, head weaving) and ataxia. In the present study, the influence of the prototypic anticonvulsant diphenylhydantoin (DPH) has been tested on the EEG and behavioural effects induced by the non-competitive NMDA antagonists phencyclidine (PCP) and dizocilpine (MK-801) and by the competitive NMDA antagonist cis-4 phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755). Even though DPH (up to 100 mg/kg IP) did not markedly affect basal cortical EEG activity, at doses of 10 100 mg/kg IP it potentiated all the EEG effects induced by the NMDA antagonists. These data support involvement of NMDA neurotransmission in the pharmacological effects of DPH. PMID- 7862862 TI - Post-training minaprine enhances memory storage in mice: involvement of D1 and D2 dopamine receptors. AB - Post-training administration of minaprine (2.5, 5 and 10 mg/kg) dose-dependently improved retention of an inhibitory avoidance response in mice. Animals receiving nine daily injections of 5 mg/kg and administered a challenge dose post-training showed an improvement in memory consolidation similar to that produced by acute injection of 10 mg/kg. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation. They were observed when drugs were given at short, but not long, periods of time after training, i.e. when the memory trace was susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or non-specific action of the drugs on retention performance, as the latencies during the retention test of those mice that had not received a footshock during training were not affected by post-training drug administration. The effects of an acutely injected dose (10 mg/kg) of minaprine as well as those of a challenge dose (5 mg/kg) of the drug administered to repeatedly treated animals were reversed by pretreatment with either selective D1 or D2 dopamine receptor antagonists SCH 23390 and (-) sulpiride administered at per se non-effective doses (0.025 and 6 mg/kg, respectively), thus suggesting that D1 and D2 receptor types are similarly involved in the effects of minaprine on memory consolidation. These results show that minaprine improves memory consolidation and that repeated drug administration leads to potentiation of this effect. Moreover, the effects of minaprine on memory consolidation are related to its dopaminergic action. PMID- 7862863 TI - Time course of the effects of adrenalectomy and corticosterone replacement on 5 HT1A receptors and 5-HT uptake sites in the hippocampus and dorsal raphe nucleus of the rat brain: an autoradiographic analysis. AB - Previous studies have shown that adrenalectomy (ADX) increases the binding of 3H DPAT to 5-HT1A receptors in the hippocampus (HIP) and this effect is partially overcome by corticosterone (CORT) replacement. The present study investigated the time course of the effects of ADX with or without CORT replacement on serotonin (5-HT) pre- and postsynaptic systems in the HIP and dorsal raphe nucleus (DR) by quantitative autoradiography. In the HIP, ADX for 7, 10 or 14 days caused a significant increase in 3H-DPAT binding in the CA1 region (pyramidal layer), CA2,3 region (molecular and pyramidal layers) and in the dentate gyrus (molecular and granular layers) which returned to control levels when measurements were made 35 days post-ADX. A decrease in 3H-DPAT binding was observed 14 days after ADX in the DR but not in the median raphe nucleus (MR). Although replacement with CORT did not lead to a reversal in 3H-DPAT binding early time points, binding was restored to control levels 7-28 days after CORT replacement in all regions of the HIP. In the DR, CORT did not cause a reversal in 3H-DPAT binding at any of the time points examined. In contrast to the effects seen on the 5-HT1A receptor subtype, no significant change was noted on the binding of 3H-CN-IMI to uptake sites for 5-HT in the HIP or DR after ADX or CORT replacement. The results of this study indicate that long-term alterations in the HPA axis lead to changes in the 5-HT1A receptor system that are both region-specific and time-dependent. PMID- 7862864 TI - Prepulse inhibition of the acoustic startle response of rats is reduced by 6 hydroxydopamine lesions of the medial prefrontal cortex. AB - Prepulse inhibition (PPI) of the acoustic startle response (ASR) is impaired by dopamine (DA) overactivity in the nucleus accumbens and anteromedial striatum. Since there is evidence that DA in the medial prefrontal cortex exerts an inhibitory control on striatal DA systems, it was investigated whether depletion of prefrontal DA reduces PPI. Rats were tested for PPI both before and after injections (2 x 1 microliter per side) of vehicle, a low (3.0 microgram/microliter) or a high (6.0 microgram/microliter) dose of 6 hydroxydopamine hydrobromide (6-OHDA) into the prefrontal cortex. Only the high dose of 6-OHDA, leading to an 87% depletion of prefrontal DA, impaired PPI. The ability of an acoustic prepulse (75 dB, 10 kHz) to reduce the response to a startle pulse (100 dB noise burst) was maintained in sham lesioned rats, but was significantly disturbed in rats lesioned with the high dose of 6-OHDA. The 6-OHDA treatment did not affect the ASR amplitude in the absence of a prepulse. The reduction of PPI in lesioned rats correlated with the extent of DA depletion. These results suggest that the DA innervation of the prefrontal cortex is involved in the modulation of the ASR and they provide further evidence for opposite actions of prefrontal and subcortical DA systems in the control of behaviour. The present findings are discussed with regard to the potential role of prefrontal DA in schizophrenia. PMID- 7862865 TI - Effects of alpha-2 adrenoceptor antagonists on rough-and-tumble play in juvenile rats: evidence for a site of action independent of non-adrenoceptor imidazoline binding sites. AB - The pharmacological specificity of alpha-2 adrenoceptor involvement in the modulation of rough-and-tumble play behavior was assessed in juvenile rats. The alpha-2 adrenoceptor antagonists idazoxan and RX821002 both increased the frequency of pinning in individually housed rats that were given a brief opportunity to play. Dorsal contacts, a measure of play solicitation, were not consistently affected by these compounds. Since RX821002 shows little affinity for non-adrenoceptor imidazoline binding sites, it is likely that the facilitation of play following administration of these two compounds is due to blockade of alpha-2 receptors. The effect of RX821002 and idazoxan is unlikely to be an artifact associated with using rats that are reared in isolation, as RX821002 also increased pinning, as well as dorsal contacts, in group-housed rats that were isolated for a short period (4h) before the play session. The alpha-1 adrenoceptor antagonist prazosin, which also binds to alpha-2B receptors, reduced the frequency of both pinning and dorsal contacts. There was a strong trend for St 587, a centrally active alpha-1 agonist, to attenuate the effect of prazosin on play. While this leaves open the possibility that prazosin may be reducing play through alpha-1 blockade, antagonist activity at alpha-2B receptors cannot be ruled out. From these data, we conclude that the facilitation of play following idazoxan and RX821002 is likely due to blockade of alpha-2A adrenoceptors. These findings add further support for a specific role of alpha adrenoceptors in the modulation of playfulness in the juvenile rat. PMID- 7862866 TI - Effects of morphine and naloxone on behaviour in the hot plate test: an ethopharmacological study in the rat. AB - The objectives of this study were: i) to analyse the effects of morphine and naloxone on the rat's behaviour in the hot plate test using an ethological approach, and ii) to compare the effectiveness of repeated versus single test paradigms. Animals received either morphine (0, 3, 6 or 9 mg/kg SC) or naloxone (0, 0.01, 0.1 or 1 mg/kg SC). For repeated hot plate measures, rats were tested before and 60, 120, 180 and 240 min following morphine treatment, as well as 30, 60, 90 and 120 min after naloxone injection. For the single test schedule, rats were tested only once 60 min after morphine or 30 min after naloxone administration, or at 60, 120, 180, 240 and 300 min after 9 mg/kg morphine treatment. Behaviour was videotaped and analysed by an ethogram and ethological techniques. A cluster analysis revealed that the most frequently displayed patterns could be categorised into exploratory sniffing reactions (walk-sniff, immobile-sniff) and noxious-evoked elements, including primary (paw-licking, stamping), escape (jumping, leaning posture) and independent (hindleg-withdrawal) patterns. During repeated tests, morphine treatment induced: i) a maximum hypoalgesic effect 60 min post-injection (noxious-evoked patterns were significantly reduced), and ii) an unexpected "thermal hyperreactivity rebound effect" after 120 min (paw-licking and hindleg-withdrawal were enhanced), although changes in hindpaw-licking are more indicative of a hyperalgesic rebound effect. Most changes were quite similar during the single test schedule at 60 and 120 min after morphine injection. With regard to naloxone treatment, jumping latency was significantly decreased during the repeated test schedule, but not on single exposure to the plate. Other elements were facilitated, however, in the single test (stamping, leaning posture, hindleg-withdrawal). The results indicated that both repeated and single tests paradigms are of value for testing the effects of morphine and naloxone on rats. However, under our conditions the single test paradigm gave a better picture of the overall effects of the drug. Learning as well as habituation and sensitization may mask certain effects during repeated tests. In conclusion, an ethological analysis of the rat's behaviour in the hot plate test following administration of morphine and naloxone has been validated in this study. PMID- 7862867 TI - The NMDA receptor antagonist dizocilpine differentially affects environment dependent and environment-independent ethanol tolerance. AB - Antagonists of the N-methyl-D-aspartate subtype of glutamate receptor have been reported to block the development of tolerance to various effects of ethanol and opiates, using paradigms in which tolerance is believed to be governed by learning. There is considerable evidence to implicate the N-methyl-D-aspartate receptor in learning processes, and therefore the ability of the antagonists to block tolerance has been attributed to their effects on learning. To evaluate this hypothesis, we compared, in C57BL/6 mice, the effect of the uncompetitive N methyl-D-aspartate receptor antagonist, dizocilpine, on environment-dependent (associative) tolerance to ethanol, which is governed by learning, and on environment-independent (nonassociative) ethanol tolerance, in which learning plays a minimal role. Environment-dependent tolerance was induced by repeated ethanol injections, and dizocilpine blocked the development of this type of tolerance to the hypothermic and incoordinating effects of ethanol. In contrast, when environment-independent ethanol tolerance was induced by feeding the mice an ethanol-containing liquid diet, dizocilpine treatment had no effect on the development of tolerance to the hypothermic, incoordinating or hypnotic effects of ethanol. The results support the hypothesis that the effect of N-methyl-D aspartate receptor antagonists on ethanol tolerance reflects the more general role of this receptor in processes involving learning and memory. PMID- 7862868 TI - SDZ 208-911, an amino-ergoline with partial dopamine agonist properties, dose dependently increases cocaine self-administration in the rat. AB - Brain dopamine neurotransmission appears to be an important component of the neural pathways involved in the maintenance of intravenous (IV) cocaine self administration in rats. The effects of a novel partial dopamine agonist, SDZ 208 911, on intravenous cocaine self-administration in rats was studied. SDZ 208-911 at a dose range of 0.025-1.6 mg/kg SC dose-dependently increased the number of lever presses and drug intake in rats exposed to limited (3-h) daily access to cocaine on a continuous reinforcement schedule (0.75 mg/kg per injection). This behavioral profile is similar to that observed following administration of dopamine antagonist drugs and has been hypothesized to reflect a compensatory increase in drug intake due to a reduction of the reinforcing efficacy of the drug, probably because of functional antagonism at the receptor site. These results suggest that dopamine partial agonists may act as functional dopamine antagonists in the face of pharmacologically induced activation of brain dopamine function. PMID- 7862869 TI - Purinergic drugs and calcium channel antagonists attenuate the withdrawal syndrome from barbital. AB - The effects of some adenosine agonists and calcium channel antagonists on the induction of tolerance to and dependence on barbital in mice have been studied. The concurrent administration of barbital and one of the following adenosine agonists, D- or L-phenylisopropyl adenosine, cyclopentyl adenosine and chloroadenosine, or the adenosine antagonists theophylline or 8 phenyltheophylline did not change the intensities of tolerance to and dependence on the barbiturate. N-ethylcarboxamide adenosine administered during the period of chronic administration of barbital significantly reduced the withdrawal syndrome. The administration of the calcium channel antagonists diltiazem, verapamil or nifedipine was also ineffective in altering the processes of tolerance and physical dependence when given concomitantly with barbital. Abstinence behavior was significantly reduced when mice were treated during the first 48 h of withdrawal from the barbiturate with either L-phenylisopropyl adenosine, N-ethylcarboxamide adenosine, nifedipine or verapamil. These results are discussed in relation to the attenuation of tolerance to and dependence on benzodiazepines induced by similar treatments. PMID- 7862870 TI - Effects of acute selective 5-HT1, 5-HT2, 5-HT3 receptor and alpha 2 adrenoceptor blockade on naloxone-induced antinociception. AB - Several studies have demonstrated a paradoxical form of antinociception induced by the repeated administration of opioid antagonists accompanied by exposure to a painful stimulus. The underlying mechanism of this naloxone-induced antinociception (NIA) is still unknown, but the results of several studies suggest that it is a non-opioid response. This study was designed to investigate serotonergic and noradrenergic involvement in NIA. Rats were treated daily with systemic injections of 5 mg/kg naloxone, followed by a 45-s hot plate test of nociception (temperature = 51.5 +/- 0.5 degree C). After rats reached plateau levels of NIA, they received a test trial in which they were treated with various doses of different selective 5-HT or alpha 2 adrenoceptor antagonists in addition to naloxone before the hot plate test. Rats treated with 0.16, 0.32 and 0.63 mg/kg pirenperone or 2.5 mg/kg ritanserin showed significant reductions in paw lick latency with respect to rats treated with vehicle. In addition, high doses of yohimbine (7.5-10 mg/kg) also effectively reversed NIA. In contrast, NIA was not affected by acute blockade of 5-HT1 or 5-HT3 receptors by methiothepin or MDL 72222, respectively, or by the alpha 2 adrenoceptor blocker idazoxan. None of the 5-HT or alpha 2 adrenoceptor antagonists had any effect on the paw lick latencies of saline-treated rats. A possible role of 5-HT2 receptors in the antinociception induced by opioid receptor blockade is discussed. PMID- 7862871 TI - Prenatal nicotine exposure increased duration of nicotine-induced analgesia in adult rats. AB - The effect of prenatal exposure to nicotine on nicotine-induced analgesia was studied in rats. The analgesic effect of a single dose of nicotine (1 mg/kg SC) was measured by the tail-flick technique, and two subsequent studies were carried out. In the first study, 7-month-old male rats, born to dams chronically treated with nicotine during pregnancy (NIC), exhibited prolonged nicotine-induced analgesia compared to matched controls. The second study was designed to explore whether rats prenatally exposed to nicotine (NIC rats) are born with an increased sensitivity to nicotine and whether there is any sex difference. The analgesic effect of nicotine was tested on control and NIC rats of both sexes once a month from 2 to 7 months of age. At an early age, male but not female NIC rats, exhibited shorter analgesic responses to nicotine than did the matched controls. With increasing age, however, the duration of nicotine analgesia began to be prolonged in NIC rats of both sexes. Significant differences between control and NIC rats were found at the age of 6 and 7 months, in both sexes. Thus, rats prenatally exposed to nicotine are not born with an increased sensitivity to the analgesic effect of a single dose of nicotine. This phenomenon develops later, during the course of life, independently of gender. PMID- 7862872 TI - Effects of chronic treatment with valproate on serotonin-1A receptor binding and function. AB - Valproate is effective in treating bipolar disorder characterized by rapid cycling or acute mania, although the mechanism of action is unclear. In contrast to other treatments for depression, 21 days of treatment in rats with valproate (1,, 200 or 400 mg/kg) did not significantly alter the hypothermia induced by 8 hydroxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT), an agonist at serotonin-1A receptors. Treatment with valproate also had no effect on radioligand binding to serotonin-1A, serotonin-2 or beta-adrenergic receptors. Based on these animal studies in frontal cortex and hippocampus, the therapeutic benefit of valproate in mood disorders does not appear to involve adaptive changes in serotonin-1A, serotonin-2 or beta-adrenergic receptor number. PMID- 7862873 TI - Raised corticosterone in the rat after exposure to the elevated plus-maze. AB - Rats given one or two 5-min trials in the elevated plus-maze had plasma corticosterone concentrations significantly higher than the home cage control group and there was no sign of habituation in the group given two trials. In rats given two plus-maze trials the corticosterone responses were significantly higher in the group given 10-min rather than 5-min trials. A previous experience of cat odour (1 week earlier) has no effect on the plasma corticosterone response, but did have an anxiogenic effect that could be detected by a decrease in the percentage of time spent on the open arms of the plus-maze. The results are discussed with reference to the nature of anxiety generated by trials 1 and 2 and by the trial duration in the plus-maze, and with respect to dissociation between behavioural and endocrinological measures. PMID- 7862874 TI - Influence of repeated cocaine exposure on the endocrine and behavioral responses to stress in rats. AB - Previous studies have determined that chronic cocaine exposure inhibits the serotonergic stimulation of hormone secretion. The present experiments were conducted to determine whether the endocrine responses to stress could be a useful approach to assess the influence of cocaine exposure on neuronal function. Male rats received twice daily injections of cocaine (1-15 mg/kg, IP) for 7 days. Animals were subsequently exposed to different stressors, i.e. conditioned emotional stress utilizing a low (0.5 mA) or high (1.5 mA) intensity footshock during training, or to immobilization stress. Immediately after the stress procedures, blood samples were collected for radioimmunoassay of plasma corticosterone, prolactin, and renin concentrations. Repeated cocaine exposure attenuated the stress-induced elevations of corticosterone and prolactin secretion, and attenuated some of the behavioral effects of the low intensity conditioned emotional stress. When exposed to the high intensity conditioned emotional stress, cocaine did not alter the endocrine or behavioral effects of stress. Finally, repeated cocaine exposure modified the immobilization stress induced elevation of renin secretion; low doses of cocaine (1 or 5 mg/kg) attenuated, while higher doses (10 mg/kg) potentiated the renin response to immobilization stress. Thus, the influence of repeated cocaine exposure on the endocrine and behavioral responses to stress appears to depend upon the type and intensity of the stressor. Compared with previous studies which found altered neuroendocrine responses to serotonin releasers and agonists following cocaine exposure, the hormonal responses to stress are less consistently modified by cocaine. PMID- 7862875 TI - Differential involvement of voltage-dependent calcium channels in apomorphine induced hypermotility and stereotypy. AB - The involvement of the voltage-dependent calcium channel in behavioral effects of apomorphine was tested in naive rats and in animals which were morphine-abstinent or were subjected to chronic electroconvulsive treatment (ECS). In naive rats a calcium channel blocker, nifedipine, which by itself does not affect locomotor activity, inhibited the locomotor stimulation induced by apomorphine, while it facilitated stereotyped behavior. Morphine-abstinent and ECS-treated rats displayed elevated responsiveness to apomorphine, reflected by hypermotility and stereotyped behavior after a dose of 1 mg/kg IP that does not produce overt behavioral effects in naive animals. Nifedipine, 5 mg/kg IP, significantly reduced hypermotility produced by apomorphine in morphine abstinent or ECS treated rats. The calcium channel blocker did not, however, antagonize enhanced stereotyped behavior. The results indicate that apomorphine hypermotility is controlled by dihydropyridine calcium channels and that enhancement of calcium channel density produced by morphine abstinence and by chronic ECS potentiates the hypermotility response. Calcium channels seem to be differently involved in control of apomorphine-induced hypermotility and stereotypy. PMID- 7862876 TI - Neuroendocrine effects of sumatriptan. AB - The neuroendocrine effects of the 5-HT receptor agonist, sumatriptan (6 mg subcutaneously), were studied in 11 healthy male subjects using a placebo controlled, cross-over design. Compared to placebo, sumatriptan significantly lowered levels of plasma prolactin but increased those of plasma growth hormone. There was no effect on plasma cortisol concentrations. The neuroendocrine effects of sumatriptan differ from those of previously described 5-HT-receptor agonists, and may be a consequence of selective activation of 5-HT1D or 5-HT1B receptors. However, the present data cannot exclude the possibility that the neuroendocrine changes reflect nonspecific stress responses or changes in pituitary blood flow. PMID- 7862877 TI - Anxiolytic effect of glycine antagonists microinjected into the dorsal periaqueductal grey. AB - To investigate if blockade of the modulatory glycine site of NMDA receptors in the dorsal periaqueductal grey (DPAG) would produce anxiolytic effects, groups of 9-14 rats received microinjections into this structure of 7-chloro-kynurenic acid (7-Cl-KY, 4 and 8 nmol) or 3-amino-1-hydroxypyrrolid-2-one (HA-966, 30 or 100 nmol), two selective antagonists at the strychnine-insensitive glycine modulatory site, and were submitted to the elevated plus-maze, an ethologically based animal model of anxiety. Both drugs increased the percentage of entries and of time spent in open arms as compared to rats receiving isotonic saline. Injections of the active compounds outside the DPAG were not effective. In another experiment microinjections of 7-Cl-KY (8 nmol) and HA-966 (100 nmol) into the DPAG raised the threshold of aversive electrical stimulation of the rat DPAG. These results indicate that microinjections of 7-Cl-KY and HA-966 into the DPAG cause anxiolytic effects in two different models of anxiety and support the proposal that NMDA-mediated neurotransmission in the DPAG may be related to anxiety and panic. PMID- 7862878 TI - One-trial tolerance to the effects of chlordiazepoxide on the elevated plus maze may be due to locomotor habituation, not repeated drug exposure. AB - The phenomenon of "one-trial tolerance" to the effects of chlordiazepoxide hydrochloride (CDP) in the elevated plus maze was re-examined. Unlike previous experiments, pre-exposure to the maze resulted in habituation and a consequential reduction in time spent on the open arms. The habituation effect was measured by recording the actual distance travelled by the rats in the maze and this was found to be significantly reduced by pre-exposure. Pre-exposure to the maze in the presence of CDP resulted in a reduced response to its "anxiolytic-like" effects (increasing time on the open arms compared to vehicle control rats). However, although the time spent on the open arms was reduced by pre-exposure, CDP significantly increased the time spent on the open arms by rats pre-exposed under a non-drugged state. These results suggest that rats do not become tolerant to the effects of CDP, but rather the reduced response to CDP after pre-exposure is due to habituation of exploratory behaviour. PMID- 7862879 TI - Discriminative stimulus and subjective effects of theobromine and caffeine in humans. AB - Theobromine versus placebo discrimination and caffeine versus placebo discrimination were studied in two consecutive experiments in seven volunteers who abstained from methylxanthines. Daily sessions involved PO double-blind ingestion of two sets of capsules sequentially, one of which contained drug and the other placebo. Subjects attempted to identify, and were later informed, which set of capsules contained the drug. In each experiment subjects were exposed to progressively lower doses. Five subjects acquired the theobromine discrimination; the lowest dose discriminated ranged from 100 to 560 mg. All seven subjects acquired the caffeine discrimination; the lowest dose discriminated ranged from 1.8 to 178 mg. A final experiment evaluated subjective effect ratings following 560 mg theobromine, 178 mg caffeine and placebo, which were administered double blind in capsules once daily, five times each in mixed sequence. Caffeine produced changes in both group and individual ratings (e.g. increased well-being, energy, social disposition and alert). Theobromine did not produce changes in group ratings but changed ratings in some subjects. Across subjects, sensitivity to caffeine discriminative effects in the discrimination experiment correlated significantly with the number and magnitude of caffeine subjective effects in the final experiment. This study documents modest discriminative effects of theobromine in humans, but the basis of the discrimination is unclear. This study suggests that commonly consumed cocoa products contain behaviorally active doses of caffeine and possibly theobromine. PMID- 7862880 TI - Acute and chronic nicotine effects on measures of activity in rats: a multivariate analysis. AB - Nicotine has been reported to increase or decrease measures of activity in rats, including locomotor activity and rearing. Nicotine dose and repeated exposure to nicotine are known to be important factors in determining the effects on locomotor behavior. Less information has been gathered on rearing and other measures of activity. Rats were tested repeatedly, once per day, in Digiscan automated activity analyzers that reported 19 measures of activity. Each rat was given the same drug and dose each day, either saline or 0.1, 0.2, or 0.4 mg/kg nicotine. The 19 measures were combined or modified to produce 14 measures that were examined using factor analysis to help select the most independent measures. Four measures were selected to describe the effects of dose and to compare day 1 results with day 5 results. Total distance moved was increased in a dose-related fashion and was greater on day 5 than on day 1. Rearing was increased at low doses and decreased at high doses on both days. Stereotypy was increased approximately the same amount by all three doses, and was greater on day 5 than on day 1. Center time was increased by the highest dose on both days. These results once again point out the influences of repeated testing and repeated nicotine exposure on behavior. They may also help to clarify why some studies have reported that both ambulation and rearing are increased after nicotine whereas others find opposite effects. PMID- 7862881 TI - Discriminative stimulus properties of cocaine: modulation by dopamine D1 receptors in the nucleus accumbens. AB - Dopamine (DA) D1 and D2 receptors are involved in mediating the behavioral effects of cocaine, including its discriminative stimulus properties. The purpose of the present study was to investigate the role of the nucleus accumbens and, in particular, accumbens DA D1 receptors in modulating the stimulus effects of cocaine. Thus, rats were trained to discriminate cocaine (10 mg/kg, IP) from saline using a two-lever, water-reinforced FR 20 drug discrimination task. In substitution tests, systemic (IP) administration of cocaine (0.625-20 mg/kg) produced a dose-related increase in cocaine-appropriate responding. Microinjections of cocaine (2.5-40 micrograms) into the nucleus accumbens also engendered dose-dependent and complete substitutions (> 80% drug-lever responding) for the systemic training dose of cocaine, whereas intra-accumbens artificial cerebrospinal fluid (1 microliter/side) produced primarily saline appropriate responding. In antagonism tests, pretreatment with the DA D1 antagonist SCH 23390 (3-12 micrograms/kg) completely antagonized (< 20% drug lever responding) a dose of cocaine (5 mg/kg) that produced greater than 90% cocaine-lever responding when given alone. Additionally, intra-accumbens injections of SCH 23390 (0.025-0.4 microgram) prior to systemic cocaine (5 mg/kg) also significantly blocked the cocaine stimulus. The present results confirm the importance of the nucleus accumbens in mediating the discriminative stimulus properties of cocaine and suggest a primary role of accumbens DA D1 receptors in modulating this behavior. PMID- 7862882 TI - An analysis of response to nicotine infusion using an automated radiotelemetry system. AB - Previous studies from our laboratory have demonstrated that chronic nicotine infusion evokes tolerance to nicotine injected IP several hours after withdrawal from chronic infusion. This method may introduce problems related to withdrawal reactions and to stress associated with handling of the animals. The studies reported here measured tolerance to nicotine in mice using an automated radiotelemetry system. DBA/2 mice were infused intravenously with saline for 4 days followed by infusion of a 4 mg/kg per h dose of nicotine for 7 days. After the nicotine treatment, the mice were infused with saline for 7 days. The nicotine was infused continuously or in four 1 mg/kg pulses, two 2 mg/kg pulses or one 4 mg/kg pulse each hour. Home cage activity and body temperature were measured throughout the treatment periods using a radiotelemetry system. Nicotine infusion produced an abrupt decrease in body temperature and activity, but this effect was totally reversed within 12 h in the continuously infused and four infusions/h treatment groups. Mice that received one or two infusions/h also showed a rapid response to nicotine that was reversed as treatment proceeded, but nicotine continued to produce a measurable effect for several days. After nicotine withdrawal, temperature and activity returned to predrug infusion values in all of the groups except those infused once per hour. This group showed depressed activity for a minimum of 3 days after nicotine treatment stopped. Thus, the kinetics of nicotine administration affected the intensity of response during continued treatment as well as activity after cessation of chronic treatment. PMID- 7862883 TI - Endogenous kappa-opioid systems in opiate withdrawal: role in aversion and accompanying changes in mesolimbic dopamine release. AB - The kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) was recently shown to potentiate certain overt withdrawal signs in morphine-dependent rats. The present study sought to further assess this phenomenon by examining the influence of nor-BNI treatment upon the conditioned place aversion associated with the naloxone-precipitated withdrawal syndrome. In addition, in vivo microdialysis studies were conducted in morphine-dependent rats to determine whether nor-BNI treatment can modify withdrawal-induced changes in basal dopamine (DA) release within the mesolimbic system. Rats were pretreated with either saline or a single dose of nor-BNI and then received ascending doses of morphine for 10 days. A withdrawal syndrome was then precipitated by the administration of naloxone (1 mg/kg SC). In rats which received chronic morphine injections, administration of naloxone produced a characteristic withdrawal syndrome and a marked aversion for an environment previously associated with naloxone precipitated withdrawal. Nor-BNI treatment potentiated most overt signs of physical dependence. This treatment also resulted in a greater withdrawal-induced place aversion. Morphine-dependent rats exhibited a marked reduction in basal mesolimbic DA release. An even greater decrease in basal DA release was observed in nor-BNI treated rats. These results suggest that endogenous kappa-systems are important in the modulation of mesolimbic DA release and the accompanying place aversion which occurs during opiate withdrawal. PMID- 7862884 TI - Psychopharmacological treatment of social phobia; a double blind placebo controlled study with fluvoxamine. AB - Previous studies have shown selective and nonselective monoamine oxidase inhibitors (MAOIs) to be effective in the treatment of social phobia. In this study we investigated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in social phobia. Thirty patients with social phobia (DSM-IIIR) were treated with the SS-RI fluvoxamine (150 mg daily) using a 12-week double-blind placebo controlled design. A substantial improvement was observed in seven (46%) patients on fluvoxamine and in one (7%) on placebo. Statistically significant effects were seen on measures of social anxiety and general (or anticipatory) anxiety in patients treated with fluvoxamine compared with placebo. The level of phobic avoidance decreased also but the difference at endpoint between fluvoxamine and placebo failed to reach statistical significance. It is concluded that treatment with the SSRI fluvoxamine has beneficial effects in patients suffering from social phobia, suggesting that serotonergic mechanisms might be implicated in social anxiety. PMID- 7862885 TI - mu-Opioid receptor and alpha 2-adrenoceptor agonist binding sites in the postmortem brain of heroin addicts. AB - The biochemical status of human brain mu-opioid receptors and alpha 2 adrenoceptors during opiate dependence was studied by means of the binding of [3H] [D-Ala2, MePhe4, Gly-ol5] enkephalin (DAGO) and [3H]clonidine, respectively, in postmortem brains of heroin addicts who had died by opiate overdose or other causes. In the frontal cortex, thalamus and caudate of heroin addicts the density (Bmax) and affinity (KD) of mu-opioid receptors were similar to those in controls. In contrast, the density of alpha 2-adrenoceptors in heroin addicts was found to be significantly decreased in frontal cortex (Bmax 31% lower), hypothalamus (Bmax 40% lower) and caudate (Bmax 32% lower) without changes in KD values. When heroin addicts were divided into two subgroups according to the presence or absence of morphine in body fluids, only the group with positive screening for morphine showed relevant decreases in brain alpha 2-adrenoceptor density (Bmax 36-48% lower), whereas the decreases in receptor density observed in the subgroup with negative screening for morphine did not reach statistical significance. The results suggest that desensitization of brain alpha 2A adrenceptors is a relevant adaptative receptor mechanism during opiate addiction in humans. PMID- 7862886 TI - Alphaxalone, a steroid anesthetic, inhibits the startle-enhancing effects of corticotropin releasing factor, but not strychnine. AB - Corticotropin releasing factor (CRF) is a 41 amino acid peptide implicated in the expression of stress- and fear-enhanced behaviors. CRF potentiates the amplitude of the startle reflex, and this effect is reversed by benzodiazepines (BDZ), suggesting that the startle-enhancing effects of CRF are modulated by changes in the GABA/BDZ receptor complex. In the present study, CRF-potentiated startle is inhibited by alphaxalone, a pregnane steroid anesthetic that is thought to act via the GABA/BDZ receptor complex. Alphaxalone (ALX) does not reduce CRF potentiated startle by producing a generalized reduction in reactivity, since blockade of CRF-stimulated startle was not accompanied by an ALX-induced reduction in baseline startle amplitude and ALX does not reduce strychnine potentiated startle. The effects of alphaxalone on CRF-potentiated startle may not be generalized to all CRF-stimulated behaviours, since alphaxalone failed to disrupt CRF-stimulated locomotor activity. CRF-potentiated startle is a useful assay for studying the effects of novel anxiolytic agents, and alphaxalone appears to be a steroid anesthetic with anxiolytic properties in this assay. PMID- 7862887 TI - Systemic administration of amperozide, a new atypical antipsychotic drug, preferentially increases dopamine release in the rat medial prefrontal cortex. AB - The putative atypical antipsychotic drug amperozide (APZ) shows high affinity for serotonin 5-HT2 receptors but only low affinity for dopamine (DA) D2 receptors. By employing microdialysis, we examined the effects of APZ on extracellular concentrations of DA in the nucleus accumbens (NAC), the dorsolateral striatum (STR) and the medial prefrontal cortex (MPC) of awake rats. A 5.0 mg/kg (SC) dose of APZ failed to affect DA concentrations in the NAC, while it increased DA outflow in the STR (by 46%) and the MPC (by 207%). A higher dose of APZ (10 mg/kg, SC) enhanced dialysate DA from the NAC and the STR by 30%, and from the MPC by 326%. Similarly, clozapine (2.5 and 10 mg/kg, SC) produced a greater release of DA in the MPC (+ 127 and + 279%) than in the NAC (+ 52 and + 98%). The selective 5-HT2 receptor antagonist ritanserin (1.5 and 3.0 mg/kg, SC) also produced a slightly higher increase of DA output in the MPC (+ 25 and + 47%) compared with the NAC (+ 19 and + 21%). In contrast, the selective D2 receptor antagonist raclopride (0.5 and 2.0 mg/kg, SC) increased DA release in the NAC (+ 65 and + 119%) to a greater extent than in the MPC (+ 45 and + 67%). These data suggest that the 5-HT2 receptor antagonistic properties of APZ and clozapine may contribute to their preferential effects on DA transmission in the MPC. Infusion of low doses (1, 10 microM, 40 min) of APZ through the probe in the DA terminal areas did not affect significantly DA outflow, while infusion of high doses (100, 1000 microM, 40 min) resulted in a more pronounced elevation of DA levels in the NAC (up to 961%) and the STR (up to 950%) than in the MPC (up to 316%). These findings indicate that the selective action of systemically administered APZ on DA in the MPC is most likely mediated at a level other than the terminal region. Taken together, the present results provide support for the notion that 5-HT2 receptor antagonism may be of considerable significance for the action of atypical antipsychotic drugs on mesolimbocortical dopaminergic neurotransmission. PMID- 7862888 TI - Effects of concurrent saccharin availability and buprenorphine pretreatment on demand for smoked cocaine base in rhesus monkeys. AB - The effects of saccharin and the opioid partial agonist buprenorphine on cocaine base smoking were evaluated in five male rhesus monkeys. Monkeys completed a sequence of responding consisting of lever-press responses maintained under a fixed-ratio (FR) schedule followed by inhalation responses (FR5) on a smoking spout to gain access to a single delivery of volatilized cocaine base (1.0 mg/kg per delivery). Monkeys could receive a maximum of ten smoke deliveries per session. In the first experiment, either saccharin (0.03% wt/vol) or water was concurrently available under an FR1 schedule through a lip-operated drinking device. As lever FR values increased from 128 to 256, 512, 1024 and 2048, the number of cocaine smoke deliveries decreased. Cocaine intake was not statistically different when water versus saccharin was concurrently available. However, as cocaine consumption decreased, saccharin intake increased demonstrating that under these conditions, saccharin was substituting for cocaine as a reinforcer. On the first day that lidocaine replaced cocaine, all of the monkeys received the maximum number of smoke deliveries (ten) and saccharin intake increased. Lever-press responding gradually extinguished over days when lidocaine (1.0 mg/kg per delivery) was available with concurrent saccharin. In the second experiment, water was concurrently available with cocaine and buprenorphine (0.01 or 0.1 mg/kg) was administered intramuscularly (IM) 30 min before the start of the session. Although pretreatment with the lower dose of buprenorphine (0.01 mg/kg) had little effect on cocaine intake overall, individual differences in cocaine intake occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862889 TI - Strain-dependent effects of post-training cocaine or nomifensine on memory storage involve both D1 and D2 dopamine receptors. AB - Post-training administration of cocaine (1-10 mg/kg) or nomifensine (1-10 mg/kg) dose-dependently improves retention of an inhibitory avoidance response in C57BL16 mice, while impairign it in the DBA/2 strain. The effects of retention performance induced by the psychostimulant and the dopamine (DA) reuptake blocker in C57BL/6 and DBA/2 mice appear to be due to an effect on memory consolidation. In fact, they were observed when drugs were given at short, but not long, periods of time after training, i.e. when the memory trace is susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or non-specific action of the drugs on retention performance, as the latencies during the retention test of those mice that had not received a footshock during the training were not affected by the post-training drug administration. The strain-dependent effects of an intermediate dose (5 mg/kg) of both cocaine and nomifensine were reversed by pretreatment with either selective D1 or D2 DA receptor antagonist SCH 23390 and (-)-sulpiride administered at per se non effective doses (0.025 and 6 mg/kg, respectively), thus suggesting that D1 and D2 receptor types are similarly involved in modulating memory processes. These results show that the effects of cocaine on memory consolidation are related to to its dopaminergic action, since they are similar to those produced by nomifensine and, what is more important, are antagonized by pretreatment with DA receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862890 TI - Effect of subcutaneous nicotine injections of EEG alpha frequency in non-smokers: a placebo-controlled pilot study. AB - The effect of two subcutaneous injections of 0.6 mg nicotine, administered 40 min apart, was compared with placebo in four non-smoking subjects in a counter balanced double-blind crossover design. The nicotine injections produced mean peak plasma nicotine concentrations of 5.3 ng/ml 10 min after the first injection and 8.5 ng/ml 10 min after the second injection. The nicotine injections produced an increase in mean dominant alpha frequency on the electroencephalogram (EEG) which was 2 Hz greater than the effect of placebo (P = 0.049) and also produced a heart-rate boost which was 8 beats per minute greater than that produced by placebo (P = 0.022). These effects on dominant alpha frequency and heart rate were most apparent in the 10 min following each nicotine injection. The increase in dominant alpha frequency found in non-smokers in this study was similar to that following nicotine inhalation in abstinent smokers in previous studies, and suggests that this is a primary effect of nicotine, rather than simply a reversal of withdrawal-induced EEG slowing. PMID- 7862891 TI - Nitrous oxide anxiolytic effect in mice in the elevated plus maze: mediation by benzodiazepine receptors. AB - In earlier research, we have hypothesized that exposure to nitrous oxide (N2O) produces an anxiolytic effect that is mediated by benzodiazepine (BZ) receptors. The present research was conducted to characterize pharmacologically the behavioral effects of N2O in comparison with a BZ standard, chlordiazepoxide (CP), in the mouse elevated plus maze. Exposure to increasing levels of N2O produced a concentration-related increase in the percent of total entries into and the percent of total time spent on the open arms, a pattern of response similar to that induced by CP. These effects on N2O and CP were both antagonized by pretreatment with the BZ receptor blocker flumazenil (FLU). In another experiment, mice made tolerant to CP also exhibited a cross-tolerance to N2O. These results support the hypothesis that the anxiolytic effect of N2O is mediated by BZ receptors. PMID- 7862892 TI - Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH DPAT) increase ethanol intake. AB - Previous work has reported that the 5-hydroxytryptamine (5-HT)1A agonist, 8 hydroxy 2-(di-n-propylamino)tetralin (8-OH DPAT), reduces ethanol intake by rats. However, as 8-OH DPAT reduces 5-HT neurotransmission, these findings are inconsistent with the proposed inhibitory role of central 5-HT neurons on ethanol intake. We examined the effect of 8-OH DPAT on ethanol, water and food intake in rats maintained on a limited access schedule using a lower dose range (6-250 micrograms/kg) and by assessing concomitant changes in behaviour. Low doses of 8 OH DPAT enhanced ethanol intake even when food and water were offered as alternatives. Suppression in ethanol intake was observed at higher doses where elements of the 5-HT syndrome were apparent. Similar observations were made in both fluid and non-fluid deprived water drinking rats, suggesting the latter effect is non-selective. Therefore 8-OH DPAT may both increase or decrease ethanol consumption in the rat depending on the dose used. PMID- 7862893 TI - The nicotinic antagonist mecamylamine precipitates nicotine abstinence syndrome in the rat. AB - Recently, a rodent model of nicotine abstinence syndrome has been developed based on observing the frequency of spontaneous behavioral signs following termination of continuous subcutaneous infusion of nicotine tartrate. In the present study, the nicotinic antagonist mecamylamine precipitated an abstinence syndrome in nicotine-dependent rats. Twelve rats were each infused for 7 days with 9 mg/kg per day nicotine tartrate in saline via Alzet osmotic minipumps; another 12 rats were sham-operated and remained nicotine-naive. Six rats from each group received 1 mg/kg mecamylamine in saline SC immediately before a 30-min observation, while the remaining six rats from each group received saline alone. Nicotine-infused rats receiving mecamylamine exhibited significantly more (P < 0.01), overall abstinence signs than all other groups. In terms of categories of signs, they displayed significantly more gasps/writhes, teeth chatter/chews, shakes/tremors and ptosis. In a second experiment utilizing only nicotine-naive rats, a far higher dose of mecamylamine (5 mg/kg sc) induced a quasi-nicotine abstinence syndrome. The results provide further validation for this rodent model of nicotine abstinence syndrome. PMID- 7862894 TI - Amphetamine-induced disruptions of latent inhibition are reinforcer mediated: implications for animal models of schizophrenic attentional dysfunction. AB - Latent inhibition (LI) is a phenomenon observed when repeated, non-reinforced presentation of a stimulus results in a retardation of subsequent conditioning to that stimulus. Several recent experiments have suggested that LI is abolished in conditioned suppression paradigms following acute, low doses of amphetamine given during pre-exposure and conditioning. Experiment 1 sought to increase the generality of this finding in an appetitive LI paradigm, using a dose of amphetamine previously shown to disrupt the LI effect in an aversive paradigm (Killcross and Robbins 1993). However, no evidence for any disruption of LI was found. Experiment 2 extended this investigation to additional, higher doses of d amphetamine, and also examined the role of reinforcer magnitude in the effect. A non-significant trend towards an attenuated LI effect was found, which was reversed by decreases in the concentration of the sucrose reinforcer. Experiments 3 and 4 investigated the influence of systemic amphetamine in aversive paradigms, with specific attention to the increased response to the aversive foot-shock reinforcer found in amphetamine-treated animals. These experiments revealed that the influence of amphetamine on the LI effect in conditioned suppression paradigms could be reversed by reducing the intensity of footshock used in conditioning, thereby paralleling the effect found in the appetitive paradigm. Therefore it is unlikely that a simple attentional account of the abolition of the LI effect in previous experiments can be sustained. PMID- 7862895 TI - Effects of the neuroleptic alpha-flupenthixol on latent inhibition in aversively- and appetitively-motivated paradigms: evidence for dopamine-reinforcer interactions. AB - Three experiments examined the influence of the dopamine (DA) D1/D2 receptor antagonist alpha-flupenthixol on the latent inhibition (LI) effect. LI is a phenomenon which is manifest when non-reinforced pre-exposure to a stimulus retards subsequent conditioning to that stimulus, and has been proposed as an animal model of the selective attentional processes that are disrupted in acute schizophrenia. Experiment 1 extended previous findings that neuroleptics enhance the LI effect in conditioned suppression paradigms in rats to alpha-flupenthixol (0.23 mg/kg). Experiment 2 demonstrated that this enhancement of the LI effect was also seen in a parallel appetitively-motivated conditioning paradigm at the same dose. In both Experiment 1 and Experiment 2, the enhancement of the LI effect by alpha-flupenthixol appeared to be accompanied by a decrease in the impact of the reinforcer (be it appetitive or aversive). Experiment 3 investigated the possible role of the reinforcer in the effect of alpha flupenthixol on the LI effect in the aversive, conditioned suppression paradigm by increasing the intensity of footshock in rats treated with alpha-flupenthixol. Increasing the intensity of the footshock completely abolished the enhancement of LI found following injection of alpha-flupenthixol, a result which could not be attributed to a floor effect. The results provide no support for interpretations of the influence of DA manipulations on the LI effect that draw parallels with deficits in selective attention observed in acute schizophrenia. PMID- 7862896 TI - Extraversion as a modifying factor in catecholamine and behavioral responses to ethanol. AB - Individual differences in catecholamine response to stress and ethanol were tested in extraverts and introverts on the basis of Eysenck's drug postulate claiming that introverts would be less susceptible to sedative drugs like ethanol. Forty-four healthy males received either 0.8 g/kg ethanol mixed into a drink of caffeine-free cola or a respective placebo and were tested with a stressful mental arithmetic task before and 40 min after the intake of the drink. Plasma catecholamines were determined from blood samples drawn at five defined intervals from an indwelling cannula and self-ratings on deactivation, relaxation, and anxiety were obtained as well as quality and quantity of performance in the arithmetic task. Results showed that there was no difference in catecholamine stress responses between introverts (Ex -) and extraverts (Ex +) before the drink, but that the intake of the fluid (both ethanol and placebo) resulted in higher norepinephrine (NE) increases in Ex - than in Ex +. The combined effects of ethanol and stress yielded larger responses of longer durations in Ex - than in Ex +. The concomitant psychological changes showed larger reductions in anxiety and increases in relaxation as well as larger decrements in quality of performance (% errors) in introverts in spite of their higher catecholamine increases. Thus, the predictions on the basis of arousal theory could not be verified experimentally and the drug postulate has to be modified in the sense that introverts probably have a higher depletion of NE in the central nervous system under physical but not under mental stress which is reflected by higher levels in the plasma and respective decreases in performance and activation. PMID- 7862897 TI - Crossmodal divided attention in rats: effects of chlordiazepoxide and scopolamine. AB - "Divided attention" is a psychological construct that hinges on assumptions about a fixed finite capacity of subjects to simultaneously process multiple sets of information. A model of a crossmodal divided attention task was developed in rats. Initially, rats were trained consecutively in operant auditory and visual conditional discrimination tasks. The final task consisted of two successive blocks of 20 trials per modality (modality certainty), followed by 60 trials comprising a semi-randomized sequence of stimuli of both modalities (auditory or visual) and qualities (flashing/pulsing or constantly turned on; modality uncertainty). In comparison to unimodal blocks of trials, performance in the mixed condition was assumed to reflect the demands on the parallel processing of two sets of stimulus-response rules. While response accuracy remained unchanged, response latencies were generally longer in the bimodal condition. Administration of scopolamine (0.03, 0.06, 0.1 mg/kg) or chlordiazepoxide (1, 3, 5, 8 mg/kg) dose-dependently increased response latencies. The scopolamine-induced increase in response latencies was greater in the mixed condition. Cost-benefit analyses demonstrated that the absolute divided attention costs (in ms) were generally higher for visual than for auditory stimuli. Both drugs produced qualitatively similar effects; however, scopolamine was more potent in increasing the absolute divided attention costs than chlordiazepoxide. These data are discussed in terms of the validity of this animal paradigm, and of hypotheses about the effects of benzodiazepine receptor agonists and muscarinic antagonists on brain information processing capacity. PMID- 7862898 TI - Negative symptoms in schizophrenia: considerations for clinical trials. Working group on negative symptoms in schizophrenia. AB - There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally. PMID- 7862899 TI - On the efficacy of alcohol placebos in inducing feelings of intoxication. AB - Placebo efficacy was monitored during three separate experiments concerned with the effects of ethanol (0.8 ml/kg body weight) on some aspect of performance: at regular intervals during experimental sessions, blood alcohol concentration was estimated using a breathalyser and subjects completed an intoxication rating. The simple placebo beverages and manipulations employed were similar to those typically described in the literature, and each experiment involved a repeated measures design. Across the three experiments, maximum mean (median) ratings during placebo sessions, expressed as a percentage of those during alcohol sessions of equivalent period, ranged between 10% (0%) and 69% (72%), and the number of subjects in each experiment for whom a placebo effect was considered to have been negligible ranged between 8% and 73%. For each treatment, intoxication ratings were higher during treatment periods which occurred first than during those which occurred second. However, this transfer effect was twice as large for placebo treatments as for alcohol treatments and, whereas in respect of the latter the effect was statistically non-significant, it was highly significant in respect of the former. The occurrence of such asymmetrical transfer of placebo efficacy suggests that repeated measures designs should be used with caution in drug studies in which a convincing placebo treatment is necessary and difficult to devise. PMID- 7862900 TI - Neonatal desipramine treatment alters free-running circadian drinking rhythms in rats. AB - Neonatal treatment with monoamine reuptake inhibitors results in a constellation of neurobehavioral alterations in adult rats that may model human depression. Since alterations in circadian rhythmicity have been reported in both depressed patients and in animal depression models, the present study examined the effects of neonatal desipramine treatment (5.0 mg/kg SC from postnatal day 7 through 22) on free-running circadian drinking rhythms. Rhythmicity was examined in constant darkness (DD), constant light (LL), and during adult desipramine treatment (0.25 mg/ml via the drinking water). Compared with saline-treated controls, neonatal desipramine lengthened free-running period in DD, blunted the period-altering effect of LL, and potentiated the period-altering effect of adult desipramine treatment. Neonatal desipramine treatment also increased circadian amplitude and spectral magnitude, but did not modify the effects of light or adult desipramine on these parameters. These results provide further evidence that behavioral depression is associated with alterations in circadian rhythmicity, and are consistent with the hypothesis that such relationships are mediated by brain monoaminergic systems. PMID- 7862901 TI - Microcatalepsy and disruption of forelimb usage during operant behavior: differences between dopamine D1 (SCH-23390) and D2 (raclopride) antagonists. AB - In an experiment designed to distinguish between the behavioral consequences of treatment with SCH-23390, a D1 dopamine receptor blocker, and raclopride, a D2 antagonist, rats were trained to perform a water-reinforced forelimb operant response. Response rate and the duration of each forelimb contact with the operandum were recorded. In addition, the durations of the rat's visits to the reward well were detected by a photobeam which was blocked by the rat's muzzle as it remained at the reward well. In a between-groups dosing design, separate groups of rats (11-13 rats/group) received SCH-23390 (0, 0.01, 0.02, 0.04, 0.08, 0.12 mg/kg, IP, 30 min) or raclopride (0. 0.05, 0.1, 0.2, 0.4, 0.8 mg/kg, IP, 30 min) for 21 consecutive days. Quantitative analyses indicated that for comparable amounts of operant rate reduction, raclopride had a significantly greater tendency than SCH-23390 to increase the duration of operant responses and to increase the maximum muzzle entry duration (i.e., to induce microcatalepsy). The results support the idea that at relatively low doses D2 antagonism is more likely than D1 antagonism to produce effects identified preclinically with extrapyramidal side effects. PMID- 7862902 TI - Effects of 5-HT3 agonists on reproductive behaviors in rats. AB - Activity at 5-HT1 and 5-HT2 receptor sites influences sexual behavior in male and female rats. 5-HT3 antagonists reportedly have no effect on copulatory activity in rats of either sex although they influence a variety of other behaviors. The effects of 5-HT3 agonists on sexual behavior are unknown. The following experiments were undertaken to assess the influence of the 5-HT3 agonists 1 phenylbiguanide (PBG) and 2-methyl-serotonin (2-Me-5-HT) on sexual behavior, when administered intracerebroventricularly. Consistent with earlier reports indicating that 5-HT1 and 5-HT2 receptor activity influences reproductive activity in a sex-dependent manner, PBG was found to facilitate male, but not female, rat sexual behavior. 2-Me-5-HT, however, failed to modify either female or male rat sexual activity. Evidence that PBG, but not 2-Me-5-HT, induces carrier-mediated dopamine release suggests that the effect of PBG in male rats is due to dopaminergic mediation. Overall, the present data indicate that 5-HT3 receptor activation has only slight effects on rat sexual behavior. PMID- 7862903 TI - Effects of GABA-ergic drugs on penile erection induced by apomorphine in rats. AB - The effects of GABA agonists and antagonists on penile erection (PE) induced by apomorphine were investigated in rats. Subcutaneous (SC) administration of apomorphine (0.01-0.1 mg/kg) induces a dose-dependent PE in rats. The maximum effect was obtained with 0.1 mg/kg of the drug. The response was decreased with increasing doses of apomorphine from 0.1 to 0.5 mg/kg. The response induced by apomorphine (0.1-0.5 mg/kg) was decreased in animals pretreated with either the GABA-A agonist muscimol or the GABA-B agonist baclofen. Combination of muscimol with baclofen caused a stronger inhibitory effect on apomorphine-induced PE. Bicuculline or picrotoxin but not phaclofen reduced the inhibitory effect of muscimol on PE induced by apomorphine, whereas phaclofen but not GABA-A antagonists decreased the inhibitory action of baclofen on apomorphine-induced PE. Pretreatment of animals with higher doses of the GABA-A antagonists bicuculline and picrotoxin or the GABA-B antagonist phaclofen elicited inhibition of apomorphine-induced PE. However, the inhibitory effects of GABA-A and GABA-B antagonists are lost on combination. Administration of GABA-A and GABA-B receptor stimulation inhibit PE induced by dopaminergic mechanism(s). PMID- 7862904 TI - Controlled comparison of nefazodone and amitriptyline in major depressive inpatients. AB - Nefazodone, a phenylpiperazine antidepressant, exhibits novel dual activity on serotonin (5-HT) neurons; it binds to 5-HT2 receptors and inhibits 5-HT reuptake. Flexible doses of nefazodone (100-400 mg/day) and amitriptyline (50-200 mg/day) were compared in 106 major depressive inpatients in a 6-week double-blind study. Results showed significant superiority of amitriptyline over nefazodone on all rating instruments: Montgomery and Asberg depression rating scale (P < 0.0001), Hamilton depression scale (P < 0.0006), Clinical Global Impressions (P < 0.0001) and Patient Global Assessment (P < 0.01). A total of 65% of patients under amitriptyline and 56% of patients under nefazodone reported adverse events during the study, with significantly more dry mouth in the amitriptyline group (39% versus 11%, P = 0.001). Modal daily doses within the last treatment week reached 242 mg with nefazodone and 124 mg with amitriptyline. The lower efficacy of nefazodone, which contradicts comparative trials with imipramine in US patients, is discussed with regard to the dose of nefazodone, probably below the optimal therapeutic range for melancholic patients, and to the clinical differences between the patient samples. PMID- 7862905 TI - Platelet 5-HT uptake sites, labelled with [3H] paroxetine, in controls and depressed patients before and after treatment with fluoxetine or lofepramine. AB - Platelet [3H] paroxetine binding was measured in 73 depressed patients and in 64 healthy volunteers. No differences were found in Bmax or Kd either overall, or when the 61 depressed subjects who had never received psychotropic drugs were analysed separately. Within the depressed group, no differences in Bmax or Kd were found between subgroups divided on the basis of endogenicity, suicidal thoughts or severity of depression. None of the subgroups differed significantly from controls. Forty of the depressed subjects were retested after 6 weeks' treatment with fluoxetine (n = 22) or lofepramine (n = 18). Treatment was not associated with any change in Bmax but a similar and significant increase in Kd was noted following treatment with either antidepressant. Neither pre- nor post treatment platelet binding parameters appeared to relate to clinical response to treatment. PMID- 7862906 TI - Behavioral and neurochemical sensitization following cocaine self-administration. AB - To determine if behavioral and neurochemical sensitization results from cocaine self-administration, rats were trained to self-administer cocaine for 20 consecutive days (26.5 +/- 2.6 mg/kg, IV/day). At 24 h or 21 days after discontinuing cocaine self-administration or yoked saline control, rats were administered an acute injection of saline IP, followed 60 min later by cocaine (15 mg/kg IP). Cocaine-induced changes in motor activity were monitored with a photocell apparatus and alterations in extracellular dopamine in the ventral striatum were measured with microdialysis. There was no difference between treatment groups in the basal level of extracellular dopamine as determined by in vitro calibration. Neither the motor stimulant response nor the increase in extracellular dopamine following an acute cocaine challenge given after 24 h of withdrawal was different between rats which self-administered cocaine and yoked saline controls. However, when the cocaine challenge was given 21 days after discontinuing cocaine self-administration both the motor response and extracellular dopamine content in the ventral straitum were significantly augmented in rats that self-administered cocaine. While no correlation was observed between the average amount of cocaine self-administered each day and the cocaine-induced alterations in extracellular dopamine at either 24 h or 21 days of withdrawl, a significant positive correlation was measured between the increase in photocell counts and the average daily cocaine administration at 21 days of withdrawl. These data show that cocaine self-administration produces an augmentation in the acute behavioral and neurochemical response to a cocaine challenge that resembles the sensitization previously demonstrated with repeated noncontingent administration. PMID- 7862907 TI - Corticosterone increases severity of acute withdrawal from ethanol, pentobarbital, and diazepam in mice. AB - It has been suggested that withdrawal from several subclasses of central nervous system (CNS) depressants involves common underlying mechanisms. For example, mice genetically selected for severe ethanol withdrawal convulsions (Withdrawal Seizure Prone or WSP) have also been found to express severe withdrawal following treatment with barbiturates and benzodiazepines. Corticosteroids appear to modulate severity of withdrawal from CNS depressants. Therefore, it was hypothesized that corticosterone would enhance withdrawal convulsions following acute ethanol, pentobarbital, and diazepam in WSP mice. Corticosterone (20 mg/kg) administered following each of these drugs significantly increased severity of handling-induced convulsions during withdrawal. Corticosterone did not affect pre withdrawal convulsion scores or handling-induced convulsions of drug-naive mice. These results suggest that withdrawal convulsions following acute ethanol, pentobarbital, and diazepam are sensitive to modulation by corticosterone and they support the hypothesis that stress may increase drug withdrawal severity. PMID- 7862908 TI - Increase of extracellular dopamine in the prefrontal cortex: a trait of drugs with antidepressant potential? AB - Drugs differing in their primary mechanism of action but having in common the ability to act as antidepressants such as fluoxetine (10 mg/kg SC), clomipramine (10 mg/kg IP), imipramine (10 mg/kg IP), desipramine (10 mg/kg IP) and (+/-) 8 OHDPAT (0.03 mg/kg SC) increase extracellular concentrations of dopamine in the rat prefrontal cortex but not in the medial nucleus accumbens. Buspirone (1 mg/kg SC) increased dopamine both in the prefrontal cortex and in the nucleus accumbens. Extracellular 5HT was increased by fluoxetine, clomipramine and imipramine but not by desipramine while 8-OHDPAT and buspirone decreased it. These results raise the possibility that the property of stimulating dopamine transmission in the prefrontal cortex has a role in the antidepressant properties of these drugs. PMID- 7862909 TI - PET studies of the uptake of (S)- and (R)-[11C]nicotine in the human brain: difficulties in visualizing specific receptor binding in vivo. AB - (S)- and (R)-[11C]nicotine were synthesized by methylation of (S)- and (R) nornicotine using [11C]methyl iodide. Following their intravenous injection in tracer doses to smoking and nonsmoking healthy males the radioactivity in arterial blood showed a sharp peak at about 1 min followed by a plateau level for the remaining 50 min of recording. Uptake in the brain, as measured by positron emission tomography (PET), was rapid with a peak at 5 min followed by a steady decline towards the end of the measurement. The regional distribution of radioactivity followed essentially the distribution of gray matter with high uptake in the cortex, the thalamus and the basal ganglia and low uptake in the pons, cerebellum and white matter. Levels of the labelled natural enantiomer, (S) [11C]nicotine, were higher than those of the synthetic enantiomer, (R) [11C]nicotine, particularly in the smokers. The time-activity curves of (S) [11C]nicotine uptake were not changed by co-administration of 1.0 mg of unlabelled nicotine with the labelled nicotine. Similarly administration of unlabelled nicotine at the peak of radioactivity, 6 min following (S) [11C]nicotine, had no effect on the time-activity curves. Thus essential criteria for visualizing receptor binding with the PET technique could not be fulfilled. Calculation of kinetic constants using a two-compartment model gave values indicating that the brain uptake of [11C]nicotine is mainly determined by the cerebral blood flow, extraction of the tracer over the blood-brain barrier and unspecific binding. Thus 11C-labelled nicotine does not seem to be a suitable tracer for PET studies of nicotinic cholinergic receptors in the human brain. PMID- 7862910 TI - Differential regulation of the behavioral effects of chlordiazepoxide. AB - Chronic administration of the benzodiazepine (BZ) receptor agonist chlordiazepoxide (CDP) produced tolerance to its motor-impairing effects but little or no tolerance to its hypothermic effects or to its amnesic effects in the radial arm maze. Male Sprague-Dawley rats were pretreated for 14 days with CDP (25 mg/kg, b.i.d., IP) or saline, and chronic treatment was maintained throughout the experiments. Tolerance was evaluated by constructing dose-response curves to CDP following chronic administration of either CDP or saline. Tolerance developed to only certain behavioral effects of CDP. Tolerance developed to the motor-impairing effects of CDP as assessed in three different procedures: rotarod, spontaneous locomotor activity, and acquisition of the step-through inhibitory avoidance response. In contrast, tolerance did not develop to the hypothermic effects of CDP. Tolerance to the amnesic effects of CDP was contingent upon the behavioral procedure. For example, tolerance developed to reductions of retention latency in the step-through inhibitory avoidance response, but not to impairment of the acquisition of radial arm maze performance. These results are consistent with the effects of chronic BZ administration in humans and demonstrate a parallel regulation of drug effects, potentially mediated by regional differences in BZ receptor subtype regulation or composition. PMID- 7862911 TI - Cognitive effects of milacemide and methylphenidate in healthy young adults. AB - Cognitive effects of the novel glycine prodrug milacemide (400 mg), the catecholaminergic agonist methylphenidate (20 mg), and placebo were evaluated in 48 healthy young adults. Throughout a 6-h drug treatment day, subjects repeatedly performed tests of target-detection vigilance, immediate and delayed verbal free recall, and Buschke Selective Reminding; total free recall and forced-choice recognition tests were administered at the end of the day. Significant improvement in both vigilance reaction time and Selective Reminding Sum Recall was observed in the methylphenidate group. Contrary to expectations, the milacemide group evidenced significant declines in both vigilance perceptual sensitivity and free-recall difference scores (delayed-immediate). Vigilance reaction times significantly decreased over repeat testing in all groups, but only the methylphenidate group differed from placebo. The reaction-time functions for milacemide and placebo were similar, suggesting arousal was not diminished under milacemide and could not account for the cognitive decrements. No significant drug effects obtained for total free recall or recognition performance. Although the glycine prodrug milacemide was ineffective as a cognitive enhancer, the involvement of the NMDA receptor in memory function reported in the literature supports continued exploration of other approaches for manipulating NMDA receptor activity. PMID- 7862912 TI - The effects of behavioral history on cocaine self-administration by rhesus monkeys. AB - The purpose of the present study was to examine whether a history of responding under schedules that generate either high or low response rates could modify previously established cocaine self-administration. Eight experimentally naive rhesus monkeys were trained to respond on one of two levers under a fixed interval (FI) 5-min schedule of intravenous cocaine (0.03 mg/kg per injection) presentation. When responding was stable a cocaine dose-response curve (saline, 0.01-0.3 mg/kg per injection) was determined. Following completion of the dose response curves, the monkeys were randomly assigned to one of two groups (n = 4/group) and trained to respond on the other lever under either a fixed-ratio (FR) 50 or inter-response times (IRT) > 30-s schedule of cocaine (0.03 mg/kg per injection) presentation. After 65 sessions responding was again maintained under the FI5-min schedule of 0.03 mg/kg per injection cocaine for 60 sessions, followed by redetermination of the cocaine dose-response curve. During the initial exposure to the FI schedule, the mean rate of responding was 4.02 (+/- 0.33) responses/min and the cocaine dose-response curve was characterized as an inverted-U shape function of dose, with peak responding at 0.03 mg/kg per injection. The FR50 schedule generated high rates (66.80 +/- 5.6 responses/min), while response rates under the IRT > 30-s schedule were low (2.62 +/- 0.2 responses/min). Following different behavioral histories, response rates under the FI5-min schedule were significantly higher for 60 sessions in FR-history monkeys compared to IRT-history subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862913 TI - Additive effects of lithium and antidepressants in the forced swimming test: further evidence for involvement of the serotoninergic system. AB - In the mouse forced swimming test (FST) pretreatment with a subactive dose of lithium (1 mEq/kg), given IP 45 min before the test, facilitated the antidepressant activity of iprindole, fluoxetine, and moclobemide (given IP 30 min before the test). These antidepressants (ADS) were not active alone in the FST in this study. Moreover, when subactive lithium was combined with a wide range of ADS, each given at subactive doses, those ADS with serotoninergic properties (e.g. imipramine, citalopram, paroxetine, fluoxetine, trazodone, mianserin, and moclobemide) significantly reduced immobility times. ADS acting primarily on noradrenaline (NA) or dopamine (DA) systems (desipramine, maprotiline, viloxazine, and bupropion) did not significantly decrease immobility when given in combination with lithium. This was also the case for RO 16 6491 [a reversible, B specific monoamine oxidase inhibitor (MAOI)], nialamide, and pargyline (both irreversible, mixed MAOIs). The anti-immobility effect of iprindole in combination with lithium suggests either a direct or indirect action on the serotonin (5HT) system by this ADS whose mechanism of action remains obscure. These results, using an animal behavioral model of depression and combining our present knowledge of the acute action of various ADS, support the hypothesis that the potentiation by lithium of ADS is via direct 5HT mechanisms, indirectly via a NA/5HT link, and/or by second messenger systems. Lithium may also facilitate the expression of antidepressant activity of ADS not active by themselves in the FST. PMID- 7862914 TI - Effects of midazolam and naloxone in rats tested for sensitivity/reactivity to formalin pain in a familiar, novel or aversively conditioned environment. AB - Rats tested for sensitivity/reactivity to formalin-induced pain in either an aversively conditioned or a novel environment displayed immediate but transient hypoalgesic responses that were insensitive to either a benzodiazepine (midazolam) or an opioid antagonist (naloxone). Exposure to the aversively conditioned, but not to the novel environment also provoked a more enduring hypoalgesic response that was abolished by either midazolam or naloxone. The results were taken to mean that fear is sufficient but not necessary for the production of hypoalgesic responses to environmental stimuli. PMID- 7862915 TI - Diazepam impairs place learning in native but not in maze-experienced rats in the Morris water maze. AB - Anxiolytic benzodiazepines have been shown to impair place learning in the Morris water maze. However, a clear-cut demonstration of a direct and specific effect on mnemonic processes has not yet been offered. In the present study, the effects of diazepam on place navigation in the Morris water maze were studied in rats. Three conditions were examined: learning, reversal learning and learning after familiarisation of animals with the maze. In view of the anxiolytic and sedative properties of diazepam, appropriate doses of the drug, i.e. those that produced an anxiolytic effect but no major motor impairment, were initially selected in the water-lick conflict and rotarod tests, respectively. Doses of 2.5 and 5 mg/kg PO increased punished drinking in the water-lick conflict test without significantly decreasing rotarod performance. These doses were then used to assess the effects of diazepam on spatial behaviour. Diazepam, at both doses, impaired place learning in behaviourally naive rats. Such an effect appeared to be transient: diazepam-treated rats eventually reached control performance. Moreover, analysis of the probe trial at the end of training revealed adoption of a spatial strategy to locate the submerged platform. Neither reversal learning nor learning after familiarisation was affected. These results do not replicate previous findings in the Morris water maze and provide some evidence that the diazepam-induced place learning deficit may be primarily anxiolytic in nature. PMID- 7862916 TI - Modulation of ethanol reinforcement by conditioned hyperthermia. AB - The present study was designed to determine whether a signal for availability of self-administered ethanol would acquire the ability to elicit a conditioned thermal response and to alter ethanol self-administration. Non-deprived male albino rats (n = 8) were exposed to a differential conditioning procedure in which brief (30-min) periods of access to sweetened ethanol on a fixed-ratio operant schedule were either signalled (CS+trials) or unsignalled (Blank+trials). A different stimulus signalled trials on which barpressing was not reinforced (CS trials). Body temperature was recorded continuously from implanted telemetry devices. As in previous studies involving experimenter-administered ethanol injections, the stimulus paired with self-administered ethanol (CS+) acquired the ability to elicit a conditioned increase in body temperature. Moreover, barpressing for ethanol was greater on signalled trials (CS+) than on unsignalled trials (Blank+), indicating that ethanol's reinforcing efficacy was altered by CS+. Ethanol self-administration was significantly correlated with the anticipatory increase in body temperature on CS+ trials (Pearson r = +0.77). When ethanol was removed, leaving sucrose alone as the reinforcer, the signal's effect on barpressing was eliminated. This finding suggests the signal's effect depended on ethanol's pharmacological properties. In general, these data are consistent with theories that attribute the signal's effect to conditioned changes in motivation to obtain ethanol or to an interaction between the conditioned response and ethanol's unconditioned effects. The specific pattern of results appears to support hypotheses linking ethanol's thermal and motivational effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862917 TI - Tolerance, cross-tolerance and dependence measured by operant responding in rats treated with triazolam via osmotic pumps. AB - Previous research has found that drugs with affinity for omega (benzodiazepine) sites differ in their abilities to produce tolerance and dependence. The present study therefore investigated the effects of ligands of omega (BZ) sites in rats that had been rendered tolerant to a benzodiazepine. Two experiments were carried out in separate groups of rats. Behavioral changes induced by chronic infusion of triazolam (3 mg/kg/day, SC, for 14 days) via osmotic pumps were studied in animals trained on a fixed ratio 10 schedule of food presentation. Control animals were implanted with pumps containing the vehicle. Test drugs were administered IP using cumulative dosing. In one experiment triazolam decreased response rates on days 1, 2 and 3 after implantation of the pumps and tolerance developed to this depressant effect. In the other experiment, vehicle and triazolam treated rats differed in their responding during chronic infusion but differences were not statistically significant on any particular day. Flumazenil (3.0-30 mg/kg) greatly decreased rates of responding on day 11 in triazolam treated rats. This effect may represent a precipitated withdrawal syndrome. However, no withdrawal effects on operant performance were observed upon pump removal. Chronic infusion of triazolam did not affect the sensitivity of rats to alpidem on day 11 (10-100 mg/kg) whereas it abolished the stimulant effect of bretazenil (0.1-1.0 mg/kg). Chronic triazolam treatment produced tolerance to the depressant effects of triazolam (1.0-3.0 mg/kg), lorazepam (0.3-3.0 mg/kg) and zopiclone (10 mg/kg) but no tolerance to those of CL 218,872 (3.0-30 mg/kg) and zolpidem (0.3-3.0 mg/kg) when tested 3-14 days after pump removal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862918 TI - Transdermal nicotine: reduction of smoking with minimal abuse liability. AB - Cigarette consumption as well as the physiologic, performance and subjective effects of the nicotine patch were evaluated in ten subjects who smoked ad libitum while residing on a residential research ward for 30 days. Nicotine transdermal systems ("patches") delivering a total of 0, 22 or 44 mg per 24 h were applied daily at a constant dose during each 7-day condition; the order of dosing conditions was varied according to a randomized, double-blind, crossover design. Nicotine patches significantly but modestly reduced spontaneous smoking and significantly increased venous plasma nicotine levels. Self ratings of patch liking, satisfaction with cigarettes and the ability to identify the patch condition did not change as a function of the nicotine dose, indicating minimal abuse liability. There were no consistent changes in the puffing pattern measures; however, in all patch conditions, subjects with extensive histories of illicit drug use smoked cigarettes faster than subjects with histories of occasional drug use. Small changes in resting heart rate, pulse and blood pressure occurred when the nicotine patch was worn. Thus large changes in venous plasma nicotine levels engender only modest changes in ad libitum cigarette consumption, measures of abuse liability and cardiovascular effects. These findings are consistent with the notion that the addictive and toxic effects of nicotine are partially determined by the rate of drug administration. PMID- 7862919 TI - Dynamics of behavioral sensitization induced by the dopamine agonist quinpirole and a proposed central energy control mechanism. AB - The study characterizes the process of sensitization induced by intermittent administrations of quinpirole (0.5 mg/kg) in rats in a large open field. Sensitization was found to be self-limiting, with all measures of behavior reaching a plateau after the tenth twice-weekly injection. Kinetics of sensitization were a simple hyperbolic function of the number of drug injections for some measures (speed of locomotion, length of locomotor bouts) but showed positive co-operativity for others (distance travelled, duration of locomotion, frequency of stops, route stereotypy), suggesting potentiation of the effect by preceding injections. The pace of sensitization varied for different behaviors: locomotor speed changed fastest in the early portion of chronic treatment; stereotypy of route changed primarily during the late phase; mouthing did not sensitize. Sensitization evolved by a cascade of changes that included: advancing the onset of locomotor activation; prolonging the duration of locomotion; establishing new maxima of observable responses; altering the mode of locomotion; raising speed, rate and length of locomotor bouts; and increasing stereotypy of travel. These observations do not substantiate the prediction that development of behavioral sensitization is associated with emergence of disorganized activity and/or fractionation of response chains. Instead, it is proposed that development of sensitization may represent a build-up and strengthening of performance, reflecting enhanced central control of energy expenditure stimulated by repeated injections of quinpirole. Furthermore, it is suggested that for at least one response, the maximum observable amount of locomotion, development of sensitization requires only D2 stimulation, independent of D1 tone. PMID- 7862920 TI - Individual differences in sugar intake predict the locomotor response to acute and repeated amphetamine administration. AB - Rats exhibit profound individual differences in their propensity to ingest sugar and in their locomotor response to AMP. Intrinsic variation in the responsiveness of mesolimbic dopamine mechanisms has been suggested to account for these individual differences. In light of this overlap, it might be expected that individual differences in one behavior would predict individual differences in the other. The present study determined whether individual differences in sugar intake would predict individual differences in the locomotor response to AMP. Male Wistar rats were divided into low and high feeders based on a median split of their sugar intake in response to saline administration and were subsequently tested for their locomotor response to either 1.0 or 1.75 mg/kg AMP in experiment 1. High sugar feeders exhibited significantly more locomotion than low sugar feeders in response to 1.75 mg/kg AMP. This difference was observed immediately after injection and continued for approximately 90 min. There was no difference between the two groups in their locomotor response to 1.0 mg/kg AMP. In experiment 2, rats receiving 1.0 mg/kg AMP in experiment 1 were tested for the development of behavioral sensitization with repeated AMP administrations. Rats were administered 1.0 mg/kg AMP across 5 test days, interspersed with days in which they received AMP treatment in their home cages to minimize conditioning effects. High sugar feeders exhibited greater behavioral sensitization than low sugar feeders with repeated AMP administration. Starting on test day 3, high sugar feeders exhibited significantly greater AMP-induced locomotor activity than low sugar feeders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862921 TI - Repeated treatment with ascorbate or haloperidol, but not clozapine, elevates extracellular ascorbate in the neostriatum of freely moving rats. AB - Acute administration of neuroleptic drugs alters the extracellular level of ascorbate in the neostriatum, and increasing evidence suggests a role for this vitamin in the behavioral, and possibly therapeutic, effects of these drugs. To shed further light on this issue, extracellular ascorbate was recorded in the neostriatum and nucleus accumbens of awake, behaving rats following chronic treatment with either classical (haloperidol) or atypical (clozapine) neuroleptics or ascorbate itself. Electrochemically modified, carbon-fiber microelectrodes were lowered in place the day after the last of 21 daily injections of either haloperidol (0.5 mg/kg, SC), clozapine (20 mg/kg, IP), sodium ascorbate (500 mg/kg, IP) or vehicle. Voltammetric measurements were obtained during quiet rest and following administration of d-amphetamine (2.5 mg/kg). Repeated treatment with either haloperidol or ascorbate elevated basal extracellular ascorbate and potentiated the amphetamine-induced increase in ascorbate release in neostriatum but not nucleus accumbens. Both treatment groups also showed a significant increase in amphetamine-induced sniffing and repetitive head movements compared to vehicle-treated animals. In contrast, repeated clozapine had no effect on extracellular ascorbate in either neostriatum or nucleus accumbens, but increased the locomotor response to an amphetamine challenge. Thus, to the extent that increases in neostriatal ascorbate exert neuroleptic-like effects, such effects are likely to parallel haloperidol rather than clozapine. PMID- 7862922 TI - Heart rate analysis in 24 patients treated with 150 mg amitriptyline per day. AB - Twenty-four patients treated with 150 mg amitriptyline per day for an episode of major depression underwent a standardized heart rate analysis (HRA) before therapy and after 14 days. The battery of cardiovascular reflex tests included the determination of the coefficient of variation (CV) while resting and during deep respiration, a spectral analysis of heart rate, the heart rate response to standing, and the Valsalva manoeuvre. The results of the initial HRA did not differ from a group of 24 normal control subjects matched for age and sex. On day 14 of treatment the patients showed significantly reduced values of heart rate variability in all tests (P < 0.0001), probably due to the anticholinergic side effects of amitriptyline. Heart rate increased from 78.1 to 93.6 bpm on average (P < 0.0001). Abnormal CV at rest was registered in 96% of the patients; during deep respiration 29% showed abnormal CV results. An abnormal spectral analysis was found in 100% of the cases (low frequency peak: 42%, mid-frequency peak: 100%, high frequency peak: 79%). The heart rate response to standing was abnormal in 75% and the Valsalva test in 33% of the cases. Eighty-eight percent of the patients fulfilled the criteria of a cardiovascular autonomic neuropathy under the conditions of amitriptyline therapy. As yet, the consequences of these changes for the patients have not been sufficiently elucidated. PMID- 7862923 TI - Effect of switching carbamazepine to oxcarbazepine on the plasma levels of neuroleptics. A case report. AB - Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs. PMID- 7862924 TI - Nicotine may relieve symptoms of Parkinson's disease. AB - Two elderly patients with Parkinson's disease were treated with nicotine gum and patch. Reliable changes in symptomatology were noted, using a single-subject, placebo-control reversal design. Improvement was associated with active nicotine dosing and involved diminished tremor and disorganized thinking in one patient and diminished bradykinesia and increased energy in the other. PMID- 7862925 TI - m-Chlorophenylpiperazine decreases food intake in a test meal. AB - We studied the effect of the 5-HT receptor agonist, m-chlorophenylpiperazine (mCPP) (0.4 mg/kg), on food intake in 12 healthy female volunteers, in a double blind placebo controlled design. Compared to placebo, mCPP significantly lowered food intake in a test meal. Treatment with mCPP also caused significant increases in ratings of nausea and light-headedness, though these effects had remitted by the time of the test meal. The results suggest that activation of brain 5-HT2C receptors may lower food intake in humans; it is also possible, however, that the hypophagic effect of mCPP in the present study could be a consequence of its adverse subjective side effects. PMID- 7862926 TI - Unlike haloperidol, clozapine slows and dampens rats' forelimb force oscillations and decreases force output in a press-while-licking behavioral task. AB - In order to detect putative differences in the behavioral effects of clozapine and haloperidol, rats were trained to use a single forelimb to exert continuous pressure on a force-sensing operandum. Behavior was maintained by presenting a water-filled dipper for consumption only as long as the force remained above a specified level (the water fountain task). Effects of clozapine (2.0, 4.0, 8.0 mg/kg) and haloperidol (0.02, 0.04, 0.08, 0.12 mg/kg) on the forelimb force oscillations manifested during the operandum pressing episodes were analyzed with power spectral analysis and other quantitative methods. All rats exhibited force oscillations with a fundamental frequency near 7 Hz. Clozapine shifted the frequency to lower values (i.e., oscillation slowing), while haloperidol shifted oscilations to slightly higher frequencies. Moreover, clozapine reduced power in the region of the spectrum above 5 Hz. In contrast, haloperidol tended to increase power in these regions. Time domain analyses of the force-time waveforms indicated that haloperidol increased force emission during the hold phase of the forelimb response, and clozapine decreased this measure. The results are congruent with the high extrapyramidal side effects of haloperidol and the lack of such effects of clozapine in the clinic. In addition, clozapine may have antitremor effects in rats as it does in humans. PMID- 7862927 TI - Positive relationship between the number of prior ethanol withdrawal episodes and the severity of subsequent withdrawal seizures. AB - One factor that has been shown to influence the severity of an ethanol withdrawal syndrome is a history of prior experience with episodes of ethanol withdrawal. It has been hypothesized that the progressive intensification of withdrawal symptoms following repeated bouts of ethanol intoxication and withdrawal may represent the manifestations of a "kindling-like" process. In mice, repeated episodes of ethanol withdrawal potentiate the severity of subsequent withdrawal seizures, even when the total amount of ethanol intoxication is equated across groups. In the current experiments, mice received 16-h bouts of continuous exposure to ethanol vapor in inhalation chambers separated by 8-h periods of abstinence. The withdrawal response was assessed by scoring handling-induced convulsions. The results demonstrated that a positive relationship exists between the number of prior episodes of ethanol withdrawal and the severity of subsequent withdrawal seizures. This conclusion was supported by both between-subject and within subject comparisons. The difference in withdrawal severity does not appear to be related to differences in the level of intoxication, since blood ethanol levels immediately preceding withdrawal testing were similar for all groups. Further, the differential withdrawal response exhibited by multiple and single withdrawal groups cannot be explained by a difference in the rate of ethanol elimination. Although the mechanism(s) remain to be determined, taken together, these results provide support for the "kindling" hypothesis of ethanol withdrawal. PMID- 7862928 TI - Nootropic effect of nicotine on carbon monoxide (CO)-induced delayed amnesia in mice. AB - The effects of nicotine on carbon monoxide (CO)-induced amnesia in mice were investigated using a step-down type passive avoidance task. Mice were exposed to CO 3 times at 1-h intervals, 7 days before the first training and retention test and 24 h after the first training session. Memory deficiency occurred in mice when training commenced more than 3 days after CO exposure (delayed amnesia): the median step-down latency in the retention test of the CO-exposed group was significantly shorter than that of the control group. Administration of (-) nicotine (15.6 and 31.3 nmol/kg, IP) 15 min before the first training session prolonged the step-down latency in the CO-exposed group, but (+)-nicotine did not. To determine whether this effect of (-)-nicotine was mediated via nicotinic cholinergic receptors, we attempted to block its action using a nicotinic acetylcholine receptor antagonist (mecamylamine). Mecamylamine (1.25 mumol/kg) blocked the effect of (-)-nicotine (31.3 nmol/kg) on delayed amnesia. Administration of (-)-nicotine (15.6-62.5 nmol/kg) immediately after the first training session failed to ameliorate learning ability in the CO-exposed group. These results suggest that (-)-nicotine potentiates the nicotinic cholinergic neuronal system and may potentiate acquisition of memory. PMID- 7862929 TI - The disruptive effects of ketamine on passive avoidance learning in mice: involvement of dopaminergic mechanism. AB - The involvement of dopaminergic mechanisms in ketamine-induced disruption of one trial step-through passive avoidance performance was assessed through the coadministration with the dopamine D1 antagonist SCH 23390, the dopamine D2 antagonist YM-091512 and the dopamine autoreceptor agonist at low doses, apomorphine, in mice. Pretraining (10 min before) administration of ketamine (0; saline, 2.5, 5 and 10 mg/kg SC) dose-dependently reduced the latency in the retention trial conducted 24 h after the training. However, ketamine did not affect the retention latency when administered immediately after the training or prior to retention. YM-09151-2 (0.01 and 0.03 mg/kg SC) and apomorphine (0.01 and 0.03 mg/kg SC), but not SCH 23390 (0.01 and 0.03 mg/kg SC), ameliorated the impaired reduction by ketamine (10 mg/kg) in a dose-dependent manner. These results suggest that ketamine obstructs the acquisition of the passive avoidance task, and that this effect is induced by stimulation of dopamine D2 receptors through dopamine release from the presynaptic terminals. PMID- 7862930 TI - Responsiveness to cocaine challenge in adult rats following prenatal exposure to cocaine. AB - Adult rats that were gestationally exposed to cocaine and control offspring were examined for their sensitivity to challenge doses of cocaine. Offspring were derived from Sprague-Dawley dams that had received subcutaneous injections of 40 mg/kg per 3 cc cocaine hydrochloride daily on gestational days 8-20, pair-fed dams that were injected with saline, and nontreated control dams. In order to investigate the sensitivity to challenge doses of cocaine, offspring were assessed in adulthood for locomotor activity, cocaine drug discrimination, and the time course of cocaine in brain tissue following acute cocaine challenge. Adult offspring prenatally exposed to cocaine were observed to exhibit a reduced sensitivity to the discriminative stimulus effects of cocaine as evidenced by a significant shift to the right in the dose-response curve of cocaine discrimination. No prenatal treatment effects were observed in terms of the temporal patterns of cocaine discrimination or with regard to brain levels of cocaine. In addition, baseline locomotor activity and locomotor responses to challenge doses of cocaine were comparable across the prenatal treatment groups. Thus, prenatal cocaine exposure reduced sensitivity of offspring to the discriminative stimulus properties of cocaine without altering either the distribution of cocaine to the brain or the sensitivity of the offspring to the locomotor stimulant effects of cocaine. PMID- 7862931 TI - Behavioural and pharmacological characterisation of the elevated "zero-maze" as an animal model of anxiety. AB - The elevated "zero-maze" is a modification of the elevated plus-maze model of anxiety in rats which incorporates both traditional and novel ethological measures in the analysis of drug effects. The novel design comprises an elevated annular platform with two opposite enclosed quadrants and two open, removing any ambiguity in interpretation of time spent on the central square of the traditional design and allowing uninterrupted exploration. Using this model, the reference benzodiazepine anxiolytics, diazepam (0.125-0.5 mg/kg) and chlordiazepoxide (0.5-2.0 mg/kg) significantly increased the percentage of time spent in the open quadrants (% TO) and the frequency of head dips over the edge of the platform (HDIPS), and reduced the frequency of stretched attend postures (SAP) from the closed to open quadrants. In contrast, the anxiogenic drug m chlorophenyl-piperazine (mCPP; 0.25-1.0 mg/kg) induced the opposite effects, decreasing %TO and HDIPS, and increasing SAP. The 5-HT1A receptor agonist 8 hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.001-0.1 mg/kg) had no effects on either %TO or HDIPS, but did decrease SAP at 0.01 mg/kg although not at higher or lower doses. Similarly, the 5-HT3 receptor antagonist, ondansetron (0.0001-1.0 mg/kg) decreased SAP and increased %TO at 0.01 mg/kg, but not at other doses. The present data suggest that a combination of the novel "zero-maze" design and a detailed ethological analysis provides a sensitive model for the detection of anxiolytic/anxiogenic drug action. PMID- 7862932 TI - Differential behavioral effects following microinjection of an NMDA antagonist into nucleus accumbens subregions. AB - Recent studies have demonstrated the existence of two distinct regions within the nucleus accumbens (N.Acc) known as "core" and "shell". In order to investigate whether the behavioral functions of excitatory amino acid receptors differed between these two subregions, rats were administered microinjections of 2-amino-5 phosphonovaleric acid (AP-5), a competitive NMDA antagonist (0, 0.05, 0.2, 0.5, 1.0 microgram/0.5 microliter) into selected central and medial regions of the accumbens. The central and medial sites were assumed to correspond approximately to core and shell subregions, respectively. The animals were tested in two exploratory tasks: the open field and a novel object test. In the open field test, AP-5 significantly decreased peripheral locomotion and center rearing frequency in the central but not the medial group. Locomotion and rearing were not affected by AP5 infusion into a control site, the anterior dorsal striatum (ADS). In the novel object test, animals were tested in the same open field, with prior habituation, and with several novel objects placed within it. In this test, infusions of AP-5 (0, 1.0 microgram/0.5 microliter) decreased the number and duration of contacts with the novel objects in the central but not the medial group. In addition, peripheral and center locomotion were decreased by AP-5 infusions into the central site, whether objects were present or not. In contrast, AP-5 infusions into the medial site elicited an increase in peripheral locomotion in both stimulus conditions. These findings provide behavioral pharmacological evidence that the central and medial subregions of the nucleus accumbens can be differentiated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862933 TI - Anticonflict and discriminative stimulus effects in the pigeon of a new methoxy chroman 5-HT1A agonist, (+)S 20244 and its enantiomers (+)S 20499 and (-)S 20500. AB - The present experiments examined the behavioral and receptor binding characteristics of new 5-HT1A methoxy-chroman derivatives in procedures known to be sensitive to the activity of 5-HT1A compounds. Key peck responding of pigeons was maintained by a 30-response fixed-ratio schedule of food delivery. In studies involving punished responding, every 30th response during one keylight stimulus also produced shock ("conflict" procedure). In drug discrimination studies, pigeons were trained to discriminate injections of the 5-HT1A agonist 8-OH-DPAT (0.3 mg/kg) from saline. Three forms of the methoxy-chroman compounds were tested: the enantiomers (+)S 20499 (0.01-3.0 mg/kg) and (-) S 20500 (0.3-5.6 mg/kg), as well as the racemic mixture (+)S 20244 (0.03-5.6 mg/kg). (+)S 20499 was approximately 10-fold more potent than (-)S 20500 in producing maximal increases in punished responding. (+)S 20244 was comparable in potency to (-)S 20500 in producing maximal increases in punished responding, but increases also occurred at much lower doses with (+)S 20244 and the magnitude of the effect with (-)S 20500 was less than that of the two other compounds. While increases in punished responding were observed with all three drugs at doses that did not affect unpunished responding, the highest doses of all drugs decreased unpunished responding. All compounds substituted for 8-OH-DPAT in the drug discrimination procedure, suggestive of 5-HT1A agonist activity. (+)S 20499 was approximately 30 fold more potent than (-)S 20500 in substituting for 8-OH-DPAT and 3-fold more potent than the racemate. All three compounds bound with high affinity to pigeon cerebrum receptor sites labelled by [3H]8-OH-DPAT. As in behavioral studies, (+)S 20499 was approximately 10-fold more potent than (-)S 20500 in displacing [3H]8 OH-DPAT (IC50 = 2.79 versus 20.3 nM). These studies demonstrate that the enantiomers of this compound, as well as the racemic mixture, are effective 5 HT1A compounds and that (+)S 20499 in particular is likely to be a clinically effective anxiolytic and/or antidepressant. PMID- 7862934 TI - Dose-dependent differences in the development of reserpine-induced oral dyskinesia in rats: support for a model of tardive dyskinesia. AB - Rats treated with reserpine develop spontaneous orofacial dyskinesia that has features similar to tardive dyskinesia (TD) in humans. In contrast to TD, however, reserpine-induced oral dyskinesia develops rapidly reaching a maximal level within 3 days at a dose of 1 mg/kg per day. The present study examined whether rats administered lower doses of reserpine would develop the oral dyskinesia at a slower rate, similar to the protracted development of TD. Rats were administered 0, 0.01, 0.05, 0.1, or 1.0 mg/kg reserpine subcutaneously every other day for 100 days. Oral dyskinesia was measured by recording the incidence of tongue protrusions for 30 min on days 1, 4, 10, 20, 40, 60, and 100. The time course of the development of reserpine-induced oral dyskinesia varied dose dependently. The response was evident within 4 days at 1 mg/kg, within 20 days at 0.1 mg/kg, within 60 days at 0.05 mg/kg, and was not evident at 0.01 mg/kg at any time during the 100 days of treatment. The protracted development of reserpine induced oral dyskinesia at the lower doses is consistent with TD. Doses of reserpine that produced an increase in tongue protrusions also produced a 90-95% depletion of dopamine and an increase in the ratio of dopamine metabolites to dopamine in the caudate-putamen. The disruption of dopamine neurotransmission may be involved in development of the oral dyskinesia. Furthermore, it is suggested that the 1 mg/kg dose of reserpine may induce neurochemical changes similar to that produced by long-term neuroleptic treatment, but at an accelerated rate, thereby providing a new efficient model of TD. PMID- 7862935 TI - Effects of fluvoxamine treatment on cognitive functioning in the alcoholic Korsakoff syndrome. AB - Eight patients suffering from the alcoholic Korsakoff syndrome (AKS) were entered in a double-blind cross-over trial of fluvoxamine 200 mg per day for 4 weeks versus matched placebo for 4 weeks. At the end of each phase, patients were assessed using a detailed neuropsychological test battery. Verbal fluency performance was significantly impaired following fluvoxamine treatment. No significant differences emerged on any of the other cognitive test measures when fluvoxamine was compared with placebo. However, two of the patients developed a major depressive episode while receiving fluvoxamine. PMID- 7862936 TI - The relationship between motor effects in rats following acute and chronic haloperidol treatment. AB - Tardive dyskinesia (TD) is a serious and sometimes irreversible side-effect to long-term neuroleptic treatment. In order to find predictors for development of TD, it would be of interest to known whether susceptibility to develop acute side effects increases the risk of TD development. The study investigated in female Sprague-Dawley rats the relationship between haloperidol-induced acute motor effects, assessed by means of the grid test and the open field test, and the chronic motor effect assessed as vacuous chewing movements (VCM). The doses of haloperidol were 1.2, 2.4 and 4.8 mg/kg IP in the acute experiments and haloperidol decanoate 38 mg/kg per 4 weeks IM in the chronic experiment. The VCM obtained at different timepoints during the 24 weeks of chronic treatment were highly correlated. However, no correlation was found between the motor effects in the acute and the chronic experiments. The study does not indicate any connection between susceptibility to acute side-effects on neuroleptics and later development of TD. PMID- 7862937 TI - Observational studies of dopamine D1 and D2 agonists in squirrel monkeys. AB - The behavioral effects of selective D1 and D2, nonselective, and indirectly acting dopamine agonists were compared in squirrel monkeys using continuous observation procedures. D1 agonists including SKF 81297, SKF 82958, and R(+)-6-Br APB produced dose-dependent increases in the frequencies of stationary postures and head movements and had little or no effect on either huddling or scratching. In contrast, SKF 75670 and R-SKF 38393, which are considered to be D1 partial agonists, had effects comparable to those of the D1 antagonist SCH 39166. That is, the D1 partial agonists increased the duration of huddling without greatly altering the frequencies of stationary postures, head movements, or scratching. Unlike the D1 agonists, the D2 agonists (+)-PHNO, quinpirole, and bromocriptine increased the frequency of scratching, but did not consistently alter other observable behaviors. The indirect dopamine agonists cocaine, GBR 12909, and d amphetamine and the nonselective D1/D2 agonist CY 208-243, but not ( )apomorphine, had effects comparable to those of D1 agonists such as SKF 81297. That is, each of these drugs increased the frequencies of stationary postures and head movements with little or no effect on scratching or huddling. Additionally, effects of the D1 agonist SKF 82958 and the indirect dopamine agonist cocaine were surmountably antagonized by the D1 antagonist SCH 39166. The present results show that: 1) behavioral effects of D1 and D2 agonists in monkeys are qualitatively different; 2) D1 agonists presumed to differ in intrinsic activity have dissimilar effects; and 3) effects of indirect dopamine agonists are comparable to those of D1 agonists with presumably high intrinsic activity. PMID- 7862938 TI - Acute pharmacodynamic tolerance to the subjective effects of cigarette smoking. AB - A brief feeling state questionnaire was completed before and after each cigarette, over a day of smoking. Feelings of stress/anxiety demonstrated a pattern of repetitive vacilation over the day, with high stress before smoking, reduced stress after smoking, and stress levels increasing again between cigarettes. There was no evidence of acute pharmacodynamic tolerance, with cigarettes leading to altered feelings of anxiety/stress over the whole day of smoking. Self-rated feelings of arousal also demonstrated a pattern of vacilation over the day, with low arousal pre-smoking increased arousal post-smoking, but arousal levels reducing again between cigarettes. The ANOVA drug x time interaction was significant, with the greatest arousal change following the first cigarette of the day. However, later cigarettes led to similar amounts of arousal change over the rest of day, thus questioning whether acute pharmacodynamic tolerance was occurring. Instead, the heightened arousal response to the first cigarette of the day may reflect the influence of two other factors. Firstly, overnight deprivation, with the first cigarette of the day leading to the greatest increase in plasma nicotine. Secondly, low early-morning arousal with its associated potential for increased arousal. Overall, therefore, there was little indication of acute pharmacodynamic tolerance to the subjective effects of nicotine. Cigarettes were associated with altered feelings of stress and arousal, over the whole day of smoking. PMID- 7862939 TI - Plasma nicotine, plasma beta-endorphin and mood states during periods of chronic smoking, abstinence and nicotine replacement. AB - Nicotine is known to release neuroendocrine substances which may subsequently reinforce smoking behavior by improving mood states. The purpose of this study was to examine changes in plasma beta-endorphin and mood states during periods of chronic smoking, abstinence from smoking, and abstinence while chewing nicotine gum. A modified A-B-A-C design was used. Normal male volunteers were randomly assigned to an experimental or control group. Over a 12-day protocol, experimental subjects smoked ad libitum for 2 days, were abstinent for 4 days, resumed smoking for 2 days, and then chewed nicotine gum for the final 4 days. Control subjects smoked ad libitum throughout the entire protocol. Results indicated that changes in plasma beta-endorphin levels were not related to changes in the four smoking conditions. Plasma nicotine and mood states were related, such that dysphoric moods increased during abstinence from smoking in comparison to the control group. To investigate further the relationships between nicotine, beta-endorphin and reinforcement for smoking, it may be necessary to characterize endogenous opioid peptide release in the central nervous system during smoking. PMID- 7862940 TI - Caffeine enhances the stimulant effect of methamphetamine, but may not affect induction of methamphetamine sensitization of ambulation in mice. AB - Methamphetamine (MAP: 1 and 2 mg/kg SC) and caffeine (CAF: 1, 3, 10 and 30 mg/kg SC) dose-dependently increased ambulation in mice. Repeated administration (5 times at 3 to 4-day intervals) of MAP, but not CAF, induced sensitization to its effect. Furthermore, the mice repeatedly receiving CAF showed no significant change in the sensitivity to MAP. Combined administration of MAP with CAF increased the effect. In the combinations of MAP (1 mg/kg) with CAF (3, 10 and 30 mg/kg), and MAP (2 mg/kg) with CAF (1 and 3 mg/kg), the effect was enhanced by the repeated administration. However, MAP sensitization was not modified by the combination with CAF in the repeated administration schedule, except in the combination of MAP (1 mg/kg) with CAF (30 mg/kg). The ambulation-increasing effects of MAP (1 mg/kg), CAF (10 mg/kg) and combination of MAP with CAF were almost equivalently inhibited by SCH 23390 (0.01 and 0.1 mg/kg SC) and YM-09151-2 (0.01 and 0.1 mg/kg SC). However, the inhibitory effects of apomorphine (0.05 mg/kg SC) and N6-(L-phenylisopropyl)-adenosine (0.1 and 0.2 mg/kg SC) were stronger for CAF than for MAP and the combination, and those of alpha-methyl-p tyrosine (200 mg/kg IP, 4 h before) and reserpine (1 mg/kg SC, 4 h before) were stronger for MAP and CAF alone than for the combination. The present results suggest that, although the combination of MAP and CAF enhances the ambulation increasing effect through an interaction at dopaminergic system, CAF may not significantly modify the induction of MAP sensitization in mice. PMID- 7862941 TI - Sedative, memory, and performance effects of hypnotics. AB - The sedative, amnestic, and performance disruptive effects of benzodiazepine (Bz) receptor selective and non-selective hypnotics were studied in 23 healthy, normal subjects, aged 26.8 +/- 1.0 years. Triazolam (0.25 and 0.50 mg), zolpidem (10 and 20 mg) and placebo were administered, double-blind, at bedtime in a repeated measures design. During an awakening 90 min later (at approximate peak concentration of each drug) a 30-min performance battery which included memory, vigilance, and psychomotor tasks was completed. Each drug and dose impaired memory (both immediate and delayed), vigilance, and psychomotor performance relative to placebo. Among active drugs impairment was greatest with zolpidem 20 mg, next triazolam 0.50 mg, then zolpidem 10 mg, and finally triazolam 0.25 mg. Next morning delayed recall was also impaired by all drugs and doses (i.e. anterograde amnesia). The amnestic and performance-disruptive effects paralleled the relative hypnotic effects of the drugs and doses. No receptor selectivity in these pharmacodynamic effects was observed. PMID- 7862942 TI - 5-HT1A receptor agonists improve the performance of normal and scopolamine impaired rats in an operant delayed matching to position task. AB - A series of experiments examined the effects of 5-HT1A ligands alone and in combination with the muscarinic antagonist scopolamine on short term working memory in the rat. The behavioural paradigm was a discrete trial, operant delayed matching to position task, with delays of 0, 5, 15 and 30 s. The 5-HT1A ligands tested were the full agonist, 8-OH DPAT (0, 0.1, 0.3 and 1 mg/kg), the partial agonist, ipsapirone (0, 1, 3 and 10 mg/kg), and the purported antagonist, NAN 190 (0, 1, 2, and 4 mg/kg). 1-PP (0, 0.1, 0.3, 1 mg/kg), the major metabolite of ipsapirone, was also tested. The lowest dose of 8-OH DPAT significantly improved matching accuracy at the longest delay, whereas the highest dose impaired matching accuracy and increased the latency to respond. Ipsapirone also significantly improved the accuracy of performance at a dose of 3 mg/kg, but the doses of 1 and 10 mg/kg did not significantly affect performance. NAN-190, at the highest dose tested (4 mg/kg), impaired matching accuracy, whereas the two lower doses did not significantly affect performance. The highest dose also increased the latency to respond. 1-PP had no effect on performance. Scopolamine HBr (0.14 mg/kg) caused a delay dependent impairment in matching accuracy, and had no effect on missed trials or the latency to respond. Low doses of 8-OH DPAT (0.1 and 0.3 mg/kg) significantly attenuated the scopolamine induced accuracy impairment, whereas 1 mg/kg 8-OH DPAT potentiated the impairment. Ipsapirone (3 mg/kg) also significantly improved the performance of scopolamine impaired rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862943 TI - Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys. AB - Dopamine (DA) D1 receptor compounds were examined in monkeys for effects on the working memory functions of the prefrontal cortex and on the fine motor abilities of the primary motor cortex. The D1 antagonist, SCH23390, the partial D1 agonist, SKF38393, and the full D1 agonist, dihydrexidine, were characterized in young control monkeys, and in aged monkeys with naturally occurring catecholamine depletion. In addition, SKF38393 was tested in young monkeys experimentally depleted of catecholamines with chronic reserpine treatment. Injections of SCH23390 significantly impaired the memory performance of young control monkeys, but did not impair aged monkeys with presumed catecholamine depletion. Conversely, the partial agonist, SKF38393, improved the depleted monkeys (aged or reserpine-treated) but did not improve young control animals. The full agonist, dihydrexidine, did improve memory performance in young control monkeys as well as in a subset of aged monkeys. Consistent with D1 receptor mechanisms, agonist induced improvements were blocked by SCH23390. Drug effects on memory performance occurred independently of effects on fine motor performance. These results underscore the importance of DA D1 mechanisms in cognitive function, and provide functional evidence of DA system degeneration in aged monkeys. Finally, high doses of D1 agonists impaired memory performance in aged monkeys, suggesting that excessive D1 stimulation may be deleterious to cognitive function. PMID- 7862944 TI - Ontogenetic effects of EEDQ on amphetamine-induced behaviors of rats: role of presynaptic processes. AB - Previous research has shown that the alkylating agent N-ethoxycarbonyl-2-ethoxy 1,2-dihydroquinoline (EEDQ) affects dopamine (DA) synthesis and metabolism in both preweanling and adult rats. In the present study, we attempted to determine the behavioral relevance of EEDQ's presynaptic actions. To that end, 17- and 90 day-old rats were injected with either EEDQ (7.5 mg/kg, IP) or its vehicle 30 min after half the rats were pretreated with the selective DA antagonists SCH 23390 and sulpiride. (SCH 23390/sulpiride pretreatment was used to protect D1 and D2 receptors from EEDQ-induced inactivation.) The behavioral effects of amphetamine (0, 0.1, 0.3 or 1.0 mg/kg, IP) were then assessed 1, 2, 4, and 8 days after EEDQ treatment. Amphetamine-induced behaviors were used to assess EEDQ's presynaptic actions, because amphetamine does not directly bind to the DA receptor, but rather releases DA from the presynaptic terminal. Further, since half of the EEDQ treated rats had a full complement of DA receptors (i.e., those rats pretreated with SCH 23390/sulpiride), EEDQ's actions in the presynaptic terminal could be dissociated from actions at pre- and postsynaptic receptors. In general, the results showed that EEDQ blocked most of the amphetamine-induced behaviors of both 17- and 90-day-old rats. Surprisingly, pretreatment with SCH 23390 and sulpiride only protected the amphetamine-induced behaviors of adult rats, but not the behaviors of 17-day-old rat pups. When considered together, these results suggest that EEDQ's presynaptic effects are not behaviorally relevant to the adult rat, but may be responsible for eliminating amphetamine-induced behaviors in the 17-day-old rat pup. PMID- 7862945 TI - Nonlinear relationship between circulating concentrations of reduced haloperidol and haloperidol: evaluation of possible mechanisms. AB - In patients taking haloperidol (HP), circulating concentrations of reduced haloperidol (RHP increase disproportionately to the dose or concentration of the parent drug. In the current study, we tested the hypothesis that the nonlinearity is due to preferential saturation of the reoxidation of RHP to HP, and two factors that could amplify the nonlinearity-concentration-dependent binding of RHP by plasma proteins, or by red blood cells. In 25 patients with schizophrenia who were taking HP, the unbound fraction of HP (0.085 +/- 0.016) and RHP (0.244 +/- 0.026) in plasma, and the blood:plasma ratio for each compound were independent of their concentration. Thus, saturable binding of RHP to plasma proteins or red blood cells can be excluded. HP reductase and RHP oxidase activity were measured in human liver cytosol and microsomal fractions, respectively. Because ketone reductase-catalysed formation of RHP is stereospecific, we examined each enantiomer of RHP separately. The Vmax for the oxidation of the S(-) and R(+) RHP enantiomers in four livers was 0.23 +/- 0.15 and 0.60 +/- 0.32 mumol/g protein per min (mean +/- SD), respectively. The Km was 110 +/- 40 and 70 +/- 10 microM, respectively. In contrast, HP reductase activity displayed greater capacity and was not saturable. The rate of production of RHP at a HP concentration of 122 microM (the limit of HP solubility) in the same livers was 2.6 +/- 0.7 mumol/g protein per min. Despite the observed nonlinearity between the enzymatic pathways in vitro, RHP concentrations in vivo are 2-3 orders of magnitude lower than the Km for oxidation of each enantiomer of RHP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862946 TI - Discriminative stimulus effects of melatonin in the rat. AB - To provide initial information on the potential mechanisms underlying the discriminative stimulus effects of melatonin, rats were trained to discriminate melatonin (150 mg/kg, IP) from saline in a two-choice discrete-trial avoidance paradigm. Stimulus generalization curves for melatonin were steep; complete generalization with melatonin occurred at 100-150 mg/kg. Triazolam generalized completely with melatonin (n = 7). Flurazepam generalized completely with melatonin in only two out of six rats; however, partial generalization was produced in the remaining four animals. The melatonin-appropriate responding produced by triazolam was antagonized completely (in six out of seven rats) by 0.3-10 mg/kg flumazenil (Ro 15-1788). In contrast, the dose of flumazenil sufficient to block completely the melatonin-like discriminative effects of triazolam failed to block the stimulus effects of the training dose of melatonin. Pentobarbital produced primarily melatonin-appropriate responding, with complete generalization with melatonin in five out of seven rats. Diphenhydramine generalized completely with melatonin in two out of seven rats; however, little or no partial generalization was observed in the remaining five rats. These results suggest that melatonin may produce its discriminative effects through sites on the GABAA-benzodiazepine receptor complex distinct from the benzodiazepine binding sites. PMID- 7862947 TI - Evidence for altered alpha 2-adrenoceptor function following isolation-rearing in the rat. AB - This study investigated central alpha 2-adrenoceptor function in differentially reared rats. Rats reared from weaning were either housed singly or in groups of five. Measurements of spontaneous ambulatory activity at 4 weeks postweaning showed that isolates were more hyperactive on exposure to a novel environment than grouped rats. alpha 2-Adrenoceptors were investigated using alpha 2 adrenoceptor agonist-induced behaviours, [3H]-idazoxan binding and measurement of forskolin-stimulated cyclic AMP accumulation. Clonidine (0.001-1.0 mg/kg IP) induced mydriasis in both groups with no difference observed in the response between the isolation and group-reared animals. Clonidine (0.01-0.5 mg/kg IP) induced hypoactivity in both groups, with the effect significantly greater in the isolation-reared rats. Idazoxan markedly attenuated both responses, confirming their induction by alpha 2-adrenoceptor stimulation. Clonidine-induced hypoactivity and mydriasis are mediated by pre- and postsynaptic alpha 2 adrenoceptors, respectively; therefore the results suggest rats reared in isolation have enhanced presynaptic but unchanged postsynaptic alpha 2 adrenoceptor function. Saturation binding experiments using [3H]-idazoxan were undertaken to determine alpha 2-adrenoceptor number (Bmax) and affinity (Kd) in membranes prepared from the frontal cortex and hippocampus. Analysis of binding data revealed an increase in receptor number in the hippocampus of isolates. Cyclic AMP accumulation was measured in hippocampal slices from differentially reared rats. Isolation-rearing did not affect cyclic AMP accumulation in response to stimulation by forskolin (30 microM). However, the selective alpha 2 adrenoceptor agonist, UK14304, produced a significantly greater inhibition of cyclic AMP accumulation in slices from isolated rats, confirming changes in alpha 2-adrenoceptor function following isolation rearing. PMID- 7862948 TI - Verticalization of behavior elicited by dopaminergic mobilization is qualitatively different between C57BL/6J and DBA/2J mice. AB - Behavioral effects of dopaminergic stimulation were evaluated in C57BL/6J mice and compared to the effects occurring in DBA/2J mice, an inbred strain with reduced densities of striatal dopamine receptors. Effects of apomorphine (0.5-64 mg/kg) alone and in combination with cocaine (30 mg/kg) were assessed using a time-sampling technique that classified climbing and leaning in separate categories. Locomotion was also assessed in a separate experiment. Climbing occurred in DBA/2J mice only at doses of apomorphine that were 16 times higher than the smallest effective dose in C57BL/6J mice; nevertheless, relative to baseline values, effects were fairly comparable. By contrast, whereas DBA/2J mice showed dose-dependent leaning under apomorphine, C57BL/6J mice exhibited little leaning even at doses not producing climbing, and only after the highest apomorphine dose was leaning significantly increased. Apomorphine was equipotent in inducing gnawing across strains, although somewhat less efficacious in DBA/2J mice. When given alone, cocaine produced significant climbing, but not leaning or gnawing, in either strain. Whereas cocaine potentiated apomorphine-induced climbing and gnawing in both strains, apomorphine-induced leaning was not consistently changed by cocaine in either strain. These effects were not indirectly due to hyperkinesia, since neither apomorphine alone nor apomorphine and cocaine in combination was stimulant; apomorphine alone reduced locomotor activity and attenuated cocaine-induced hyperkinesia. The present data do not support a unitary, purely quantitative, account of insensitivity to dopaminergic stimulation based upon low densities of striatal dopamine receptors in DBA/2J mice. Rather, this constellation of results is suggestive of qualitative interstrain dissimilarities in dopaminergic responsiveness that could reflect organizational differences in receptor populations. PMID- 7862949 TI - The neurosteroid pregnenolone sulfate blocks NMDA antagonist-induced deficits in a passive avoidance memory task. AB - The neurosteroid pregnenolone sulfate (PS) has been recently shown to positively modulate NMDA receptors and to have memory enhancing properties in mice. In the present study, we examined the ability of PS to increase retention performance and to reduce deficits induced by a competitive NMDA receptor antagonist, the 3 ((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), in a step-through passive avoidance task in rats. Pretraining administration of PS (0.84-1680 pmol, ICV) had minimal effects on retention performance assessed 24 h after training, while CPP significantly decreased retention performance at the doses of 1.2 and 1.6 nmol (ICV). However, when administered in combination with CPP (1.2 nmol), PS (0.84-840 pmol, ICV) dose-dependently blocked the deficit in passive avoidance response induced by the NMDA antagonist. At the dose of 840 nmol, PS also significantly reduced the motor impairment induced by CPP (1.2 nmol). The blockade of CPP-induced behavioral deficits by PS may result from its positive modulatory action at NMDA receptors. PMID- 7862950 TI - Motivational properties of ethanol in mice selectively bred for ethanol-induced locomotor differences. AB - Ethanol-induced locomotor stimulation has been proposed to be positively correlated with the rewarding effects of ethanol (Wise and Bozarth 1987). The present experiments provided a test of this hypothesis using a genetic model. Three behavioral indices of the motivational effects of ethanol (drinking, taste conditioning, place conditioning) were examined in mice from two independent FAST lines, selectively bred for sensitivity to ethanol-induced locomotor stimulation, and mice from two independent SLOW lines, selectively bred for insensitivity to ethanol-induced locomotor stimulation. In a single-bottle procedure, mice were allowed access to drinking tubes containing ethanol in a concentration (1-12% v/v) that increased over 24 consecutive days. FAST mice consumed greater amounts of ethanol solution. In a two-bottle procedure, mice were allowed access to tubes containing water or various concentrations of ethanol (2-8% v/v) over 6 days. FAST mice generally showed greater preference for ethanol solutions than SLOW mice. In a conditioned taste aversion procedure, mice received access to saccharin solution followed by injection of 2.5 g/kg ethanol (IP). SLOW mice developed aversion to the saccharin flavor more readily than FAST mice. In a series of place conditioning experiments, tactile stimuli were paired with various doses of ethanol (0.8-2.0 g/kg). During conditioning, FAST mice showed locomotor stimulation after 1.0, 1.2 and 2.0 g/kg ethanol while SLOW mice did not. During testing, mice conditioned with 1.2 g/kg and 2.0 g/kg ethanol showed conditioned place preference, but there were no line differences in magnitude of preference. These results indicate that genetic selection for sensitivity to ethanol-stimulated activity has resulted in genetic differences in ethanol drinking and ethanol-induced conditioned taste aversion but not ethanol-induced conditioned place preference. Overall, these data provide mixed support for the psychomotor stimulant theory of addiction. PMID- 7862951 TI - Individual differences in behavior following amphetamine, GBR-12909, or apomorphine but not SKF-38393 or quinpirole. AB - Subjects that respond more to a novel environment show a greater locomotor response to drugs of abuse such as cocaine and amphetamine. The current study was performed to examine differences between high (HR) and low (LR) responding rats to a novel environment following administration of amphetamine, a selective dopamine uptake blocker (GBR-12909), a nonselective dopamine agonist (apomorphine), and selective dopamine D1 and D2/D3 agonists. A behavioral checklist and a rating scale were used to determine the behavioral arousal caused by administration of amphetamine (0, 0.5, 2.0, and 8.0 mg/kg), GBR-12909 (0, 1.25, 5.0, and 20.0 mg/kg), apomorphine (0, 0.1, 0.3, and 1 mg/kg), SKF 39393 (0, 2.5, 10, and 40 mg/kg), or quinpirole (0, 0.05, 0.5, and 5.0 mg/kg). The five drugs produced behavioral activation profiles distinct from each other. Following amphetamine administration, both HR and LR subjects showed dose dependent increases in behavioral arousal. The behaviors primarily affected were sniffing, locomotor activity, rearing, and oral activity. HR rats showed a greater overall behavioral response to amphetamine administration compared with LR rats and there were differences in specific behaviors between the two groups. Following GBR 12909 administration, all subjects showed dose dependent increases in sniffing, locomotor activity, and rearing. Differences between HR and LR were observed in sniffing, locomotor activity, and rearing behaviors. HR and LR both showed dose dependent increases in behavior following apomorphine administration. HR showed greater behavioral activation after apomorphine than LR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7862952 TI - Investigations of fetal development models for prenatal drug exposure and schizophrenia. Prenatal d-amphetamine effects upon early and late juvenile behavior in the rat. AB - Recent evidence suggests that mid-pregnancy is a critical period for production of fetal abnormalities that cause behavioral and neuropathological changes in adult offspring. The present experiments provide an animal model of these effects by treating pregnant Sprague-Dawley rats during gestational days 11-14 with d amphetamine (AM). Offspring were tested for neurological signs, foraging activity, reversal learning, and sensitivity to amphetamine challenge. In the Early Juvenile period, postnatal days (PND) 20-30, female AM offspring initially showed reductions in rearing, holepoking, and midfield activity. On later trials, and as young adults, AM females showed signs of locomotor hyperactivity despite continued poor foraging efficiency, and were also more sensitive to a 1.0 mg/kg d amphetamine challenge. AM males showed initially slower and more perseverative responding than controls, but then developed excessive response switching. These changes continued during tests for Retention, Reversal, and Extinction in the Late Juvenile/Early Adult stage (PND 50-90), when both AM-exposed sexes showed increased eating time, significantly more perseverative lateral turning preference (right or left), and slower reversal learning than controls. Behavioral data were consistent with aberrations in thalamo-frontal and mesolimbic/nigrostriatal projection systems that have been reported in AM animals and which are also affected by maternal drug abuse and schizophrenia. PMID- 7862953 TI - Effects of SR 48692, a selective non-peptide neurotensin receptor antagonist, on two dopamine-dependent behavioural responses in mice and rats. AB - One major mechanism underlying the central action of neurotensin is an interaction with the function of dopamine (DA)-containing neurons. In addition, direct or indirect DA agonists have been reported to promote neurotensin release. We have found that SR 48692, a non-peptide neurotensin receptor antagonist (0.04 0.64 mg/kg orally), antagonizes (50-65%) yawning induced by apomorphine (0.07 mg/kg SC) or bromocriptine (2 mg/kg IP) in rats, and turning behaviour induced by intrastriatal injection of apomorphine (0.25 micrograms), (+) SKF 38393 (0.1 micrograms), bromocriptine (0.01 ng) or (+) amphetamine (10 micrograms) in mice. Other apomorphine-induced effects in mice and rats such as climbing, hypothermia, hypo- and hyper-locomotion, penile erections and stereotypies were not significantly modified by SR 48692. Taken together, these data suggest that neurotensin may play a permissive role in the expression of some but not all behavioural responses to DA receptor stimulation. PMID- 7862954 TI - The upcoming metamorphosis in academic medicine. PMID- 7862955 TI - von Hippel-Lindau disease: genetic, clinical, and imaging features. AB - von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that causes retinal hemangioblastomas, hemangioblastomas of the central nervous system, endolymphatic sac tumors, renal cell carcinomas, pancreatic cysts and tumors, pheochromocytomas, and epididymal cystadenomas, among other less common manifestations. Although this entity has been recognized for almost 70 years, recent developments in the genetics and imaging of VHL disease have greatly improved understanding of the disease and its natural history. This review describes the major events that led to the discovery of the gene for VHL and will familiarize the reader with recent developments in the magnetic resonance Imaging, computed tomographic, and ultrasound findings of this entity. Despite advances in the genetic understanding of this disease, imaging techniques will continue to play a major role in the diagnosis, management, and treatment of VHL. PMID- 7862956 TI - Importance of imaging demonstration of neoplastic invasion of laryngeal cartilage. PMID- 7862957 TI - Staging of prostatic cancer: accuracy of MR imaging. PMID- 7862958 TI - U.S. radiologists' satisfaction in their profession. AB - PURPOSE: To determine characteristics associated with differences among radiologists in professional satisfaction and the effect of satisfaction on career plans. MATERIALS AND METHODS: The American College of Radiology surveyed 2,804 radiologists and nuclear medicine specialists in the United States. Single variable and multivariate analyses were performed. RESULTS: Sixty-five percent of radiologists were currently satisfied with their profession; 31% were more satisfied than they were 5 years ago, 32% felt the same, and 37% were less satisfied. Current satisfaction was most likely for radiologists with a diagnostic radiology subspecialty, board certification, age over 45 years, an academic practice, a salaried position, a full-time practice, urban location, and location in the West. Professional satisfaction relative to that 5 years ago was particularly high for (among others) young radiologists. Poorly satisfied radiologists were more likely to plan a career change and eventual part-time work. Female radiologists were as satisfied as males. CONCLUSION: This study identifies sources of radiologists satisfaction and dissatisfaction and effects of satisfaction on career plans. PMID- 7862959 TI - Walter Dandy and the history of ventriculography. PMID- 7862960 TI - Neoplastic invasion of the laryngeal cartilage: comparison of MR imaging and CT with histopathologic correlation. AB - PURPOSE: To compare the usefulness of computed tomography (CT) and gadolinium enhanced magnetic resonance (MR) imaging in the detection of neoplastic invasion of laryngeal cartilage. MATERIALS AND METHODS: In a prospective study, 53 patients with carcinoma of the larynx or piriform sinus underwent CT and MR imaging before total or partial laryngectomy. The findings at imaging and pathologic examination were compared. RESULTS: At histologic examination, neoplastic invasion of cartilage was present in 34 patients and absent in 19. MR imaging was more sensitive than CT (89% vs 66%; P = .001). Inflammatory changes and fibrosis, however, were indistinguishable from tumor on MR images, resulting in overestimation of neoplastic invasion in a large number of patients. Therefore, MR imaging was less specific than CT (84% vs 94%; P = .004). CONCLUSION: MR imaging is more sensitive than CT in detecting neoplastic invasion of cartilage, but the inability to differentiate between nonneoplastic inflammatory changes and tumor with MR imaging leads to overestimation of neoplastic invasion. PMID- 7862961 TI - Cerebral dural arteriovenous fistulas: clinical and angiographic correlation with a revised classification of venous drainage. AB - PURPOSE: To review the symptoms and progression of dural arteriovenous fistulas (AVFs) and correlate the findings with various angiographic patterns. MATERIALS AND METHODS: Patterns of venous drainage allowed classification of dural AVFs into five types: type I, located in the main sinus, with antegrade flow; type II, in the main sinus, with reflux into the sinus (IIa), cortical veins (IIb), or both (IIa + b); type III, with direct cortical venous drainage without venous ectasia; type IV, with direct cortical venous drainage with venous ectasia; and type V, with spinal venous drainage. RESULTS: Type I dural AVFs had a benign course. In type II, reflux into the sinus induced intracranial hypertension in 20% of cases, and reflux into cortical veins induced hemorrhage in 10%. Hemorrhage was present in 40% of cases of type III dural AVFs and 65% of type IV. Type V produced progressive myelopathy in 50% of cases. CONCLUSION: This classification provides useful data for determination of the risk with each dural AVF and enables decision-making about the appropriate therapy. PMID- 7862962 TI - Cerebral arteriovenous malformations: flow quantitation by means of two dimensional cardiac-gated phase-contrast MR imaging. AB - PURPOSE: To test two-dimensional cardiac-gated phase-contrast (2DGPC) magnetic resonance (MR) imaging in the evaluation of cerebral arteriovenous malformations (AVMs) and the alterations in flow that accompany embolization therapy. MATERIALS AND METHODS: A 2DGPC sequence was used to measure flow velocity in the feeding vessels and corresponding contralateral vessels (CCVs) of seven patients (six men and one woman, 21-55 years of age; mean, 37 years) with cerebral AVMs and in the vessels of four healthy volunteers (all men; mean age, 22 years). RESULTS: In the patients, the flow in the feeding vessels exceeded the flow in the CCVs by a margin far greater than the asymmetry in flow in the volunteers. The mean reduction in flow after embolization was 54.9% +/- 11.1 in embolized feeding vessels (n = 6) and 5.3% +/- 2.8 in nonembolized vessels (n = 3). Postembolization flow enhancement was observed in the CCV (n = 2), which suggests a degree of autoregulatory dysfunction. CONCLUSION: This technique can be used to evaluate the flow patterns of AVMs and the hemodynamic changes that occur with embolization. PMID- 7862963 TI - Brain mapping with functional MR imaging: comparison of gradient-echo--based exogenous and endogenous contrast techniques. AB - PURPOSE: To compare directly the two most widely used methods of functional magnetic resonance (MR) imaging--dynamic contrast material-enhanced MR imaging and blood oxygenation level-dependent (BOLD) MR imaging. MATERIALS AND METHODS: Five healthy volunteers underwent dynamic contrast-enhanced and BOLD MR imaging with a conventional 1.5-T MR unit during visual stimulation and a dark control state. BOLD studies were performed with a gradient-echo sequence, and dynamic MR imaging was performed with an echo-shifted gradient-echo sequence after intravenous administration of a bolus of gadopentetate dimeglumine. RESULTS: A significantly greater percentage signal change was found with dynamic MR imaging than with the BOLD technique. The extent of area activated was also significantly greater. CONCLUSION: With standard clinical imagers and these gradient-echo-based techniques, greater percentage activation and area of activation can be achieved with dynamic MR imaging than with BOLD MR imaging. PMID- 7862964 TI - Cerebral metabolite patterns in dialysis patients: evaluation with H-1 MR spectroscopy. AB - PURPOSE: To analyze metabolic changes in the brain of patients undergoing dialysis. MATERIALS AND METHODS: Sixteen patients undergoing hemodialysis, 10 patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and 42 healthy volunteers underwent magnetic resonance (MR) spectroscopy and MR imaging. Spectra were obtained from one occipital gray matter voxel and one parietal white matter voxel. Changes in N-acetylaspartate (NAA), choline (Cho), myo-inositol and glycine (Myo), and creatine (Cr) were analyzed and the results presented as ratios, with Cr as the reference. RESULTS: Three abnormalities were observed in the spectra of the hemodialysis patients: (a) significant elevation of the Cho/Cr ratio in gray matter, (b) significant elevation of the Myo/Cr ratio in gray matter, and (c) significant reduction of the NAA/Cr ratio in gray and white matter. The strongest metabolic alterations were found in cortical gray matter. In CAPD patients, only gray matter Cho/Cr ratio was significantly elevated. An increased frequency of focal white matter lesions was observed on MR images in the dialysis patients. CONCLUSION: Proton MR spectroscopy is useful for in vivo monitoring of metabolic alterations in the brain due to chronic dialysis. PMID- 7862965 TI - The striated cerebellum: an MR imaging sign in Lhermitte-Duclos disease (dysplastic gangliocytoma). AB - PURPOSE: To correlate the magnetic resonance (MR) imaging features of and histologic findings in Lhermitte-Duclos disease (LDD) (dysplastic gangliocytoma). MATERIALS AND METHODS: MR imaging and histologic data from eight patients with the diagnosis of LDD were retrospectively reviewed. Gross pathologic specimens were also available in one case. Contrast material-enhanced MR images were obtained in seven of the eight patients. RESULTS: At MR imaging, a non-enhancing mass in the cerebellar hemisphere was characterized by a striated pattern of hyperintensity on T2-weighted images and corresponding hypointensity on T1 weighted images, which represented the abnormally thickened folia. None of the masses demonstrated enhancement. CONCLUSION: Most other cerebellar masses destroy the folial pattern and show enhancement. The nonenhancing striated MR appearance of thickened folia in patients with LDD is distinctive and should suggest this diagnosis. PMID- 7862966 TI - Embolization of carotid cavernous fistula by means of direct puncture through the superior orbital fissure. AB - PURPOSE: To embolize carotid cavernous fistulas (CCFs) by means of transorbital puncture of the cavernous sinus (CS) and the cavernous segment of the internal carotid artery (ICA) through the superior orbital fissure. MATERIALS AND METHODS: Five patients with CCF were treated with embolization of the CS, and six were treated with embolization of both the CS and the cavernous portion of the ICA after transorbital puncture. All except one had previously undergone occlusion of the ipsilateral proximal ICA before direct transorbital puncture. RESULTS: The fistulas in these cases were all obliterated completely. Only two patients had temporary ptosis. No other remarkable complications were noted. The patent ICA on the side of the fistula in one patient remained patent after embolization. CONCLUSION: Direct transorbital puncture through the superior orbital fissure is an alternate treatment for CCF, especially when the ipsilateral ICA has been occluded. PMID- 7862967 TI - Fetal cerebral ventricular atrium: difference in size according to sex. AB - PURPOSE: To determine whether the diameter of the fetal lateral ventricular atrium is larger in male than in female fetuses. MATERIALS AND METHODS: The atrial diameter in 219 fetuses retrospectively identified from a consecutive group of healthy newborns was measured without knowledge of the subject's sex. RESULTS: Atrial size demonstrated a near-normal distribution, with mean size for all subjects 6.1 mm +/- 1.3 (standard deviation). When separated by sex, the mean atrial diameter of 122 female fetuses was 5.8 mm +/- 1.3, and the mean atrial diameter of 97 male fetuses was 6.4 mm +/- 1.3. The difference in mean size is statistically significant (P < .005). CONCLUSION: Male fetuses have a slightly larger atrial size than female fetuses. This discovery has implications for defining the upper limit of normal for fetal ventricular atrial size. PMID- 7862968 TI - Use of liquid ventilation with perflubron during extracorporeal membrane oxygenation: chest radiographic appearances. AB - PURPOSE: To assess the effectiveness of performing liquid ventilation with perflubron in neonates with severe respiratory failure or pulmonary hypertension who receive extracorporeal membrane oxygenation (ECMO) life support. MATERIALS AND METHODS: We studied an infant (aged 1 month) and a neonate with respiratory failure who underwent ECMO and liquid ventilation with perflubron, which was slowly instilled via an endotracheal tube (in the infant, 40 mL for more than 1 hour; in the neonate, 28 mL within 1 hour). RESULTS: The infant survived termination of ECMO support and has been breathing room air since 6 months of age. The neonate died soon after ECMO support was withdrawn. CONCLUSION: A minority of neonates or infants with severe respiratory failure or pulmonary hypertension do not respond adequately to treatment with ECMO and are almost certain to die with termination of ECMO support. Liquid ventilation with perflubron offers a potential salvage therapy in this patient population. In addition, perflubron is a good contrast agent to use in the evaluation of neonatal pulmonary abnormalities. PMID- 7862969 TI - Nontraumatic pediatric musculoskeletal MR imaging: comparison of conventional and fast-spin-echo short inversion time inversion-recovery technique. AB - PURPOSE: To compare conventional short inversion time inversion-recovery (STIR) with fast spin-echo (FSE) STIR techniques to evaluate suspected nontraumatic musculoskeletal abnormalities. MATERIALS AND METHODS: Thirty STIR and FSE-STIR examinations in 26 pediatric patients with suspected nontraumatic musculoskeletal abnormalities were prospectively evaluated. Qualitative (subjective) and quantitative (five-point rank score) analyses of the images were performed. RESULTS: FSE-STIR was faster than STIR (mean, 2 minutes 25 seconds and 6 minutes 35 seconds, respectively). Fat suppression was slightly better with STIR. Image degradation due to motion was judged similar. Lesion contrast to muscle was slightly better with STIR than FSE-STIR, and lesion contrast to fat was equivalent. Qualitatively, lesion conspicuity was similar: All lesions were seen with both techniques. CONCLUSION: FSE-STIR can replace STIR when an inversion recovery fat-suppression sequence is desired. Considerable imaging time is saved. PMID- 7862970 TI - Volume detection threshold: quantitative comparison of computed radiography and screen-film radiography in detection of pneumothoraces in an animal model that simulates the neonate. AB - PURPOSE: To quantitatively compare computed radiography (CR) and screen-film radiography (SFR) in the detection of pneumothorax in an animal model that simulates the neonate. MATERIALS AND METHODS: Three rabbits underwent placement of 5-F catheters in the right pleural space. Eight CR and eight SFR images were obtained. Volume-controlled pneumothorax was induced by incrementally injecting 4 cm3 of air (24 cm3 total) and four CR and four SFR images were obtained after each injection. Four radiologists blindly viewed the images twice (eight readings per image, 1,600 total observations). A dichotomous yes-no score for the presence of pneumothorax was used to calculate the volume detection threshold (VDT), defined as the air volume at which 50% of the pneumothoraces can be detected. The authors plotted the likelihood of a pneumothorax against the air volume by using the confidence indicator. RESULTS: Intraobserver VDT values for CR and SFR were not significantly different. CONCLUSION: CR is as accurate as SFR in the detection of pneumothorax in this quantitative animal model. PMID- 7862971 TI - Focused US system for MR imaging-guided tumor ablation. AB - PURPOSE: To measure the performance characteristics of a focused ultrasound (US) system for magnetic resonance (MR) imaging-guided tumor ablation. MATERIALS AND METHODS: The authors constructed a focused US system for MR imaging-guided tumor ablation. The location of the heated region and thermal dose were monitored with temperature-sensitive MR images obtained in phantoms and rabbit skeletal muscle after application of each sonic pulse. RESULTS: The region heated by the focused ultrasound beam was within 1 mm of that observed on temperature-sensitive fast gradient-echo MR images of in vivo rabbit skeletal muscle. Analysis of heat flow and the rate of coagulation necrosis provided an estimate of the size of the ablated region that was in agreement with experimental findings. CONCLUSION: MR imaging provides target definition and control for thermal therapy in regions of variable perfusion or in tissues that are not well characterized. PMID- 7862972 TI - Strecker stent implantation in iliac arteries: patency and predictive factors for long-term success. AB - PURPOSE: To evaluate Strecker stent implantation in iliac arteries. MATERIALS AND METHODS: Sixty-four iliac arteries with Strecker stents were prospectively studied. Stents were placed for dissection (n = 31), total occlusion (n = 28), unsatisfactory results (n = 3) or restenosis (n = 1) after percutaneous transluminal angioplasty, and a calcified atherosclerotic lesion that bulged into the lumen (n = 1). RESULTS: Stent placement was successful in 63 arteries (98%). The overall complication rate was 12% (n = 8). During follow-up, three patients died. The stent was compromised in 18 cases because of hyperplasia (n = 10) or occlusion (n = 8). The primary patency rate was 84% at 1 year and 69% at 2 years; the secondary patency rate was 90% at 1 year and 81% at 2 years. Initial dissection (P = .046), a length of 60 mm or less for the stent region (P = .007), and total covering of the abnormal segment with the stent (P = .03) were significant predictive factors for good, long-term results. CONCLUSION: Use of the Strecker endoprosthesis appears useful but not ideal. Determination of predictive factors for long-term success may help identify indications for its use. PMID- 7862973 TI - Primary stent placement for chronic iliac artery occlusions: follow-up results in 103 patients. AB - PURPOSE: To report results of primary stent placement for treatment of chronic iliac artery occlusions. MATERIALS AND METHODS: The authors placed 154 primary stents in 103 patients with iliac artery occlusions of at least 3 months duration. Mean length of the occluded segments was 5.1 cm. All patients had symptoms, with claudication or trophic changes. Mean ankle-arm index at rest was 0.48. Follow-up included angiography, Doppler ultrasound, and clinical examination. RESULTS: Ninety-nine patients demonstrated clinical improvement, with relief or improvement of claudication. Complications that required percutaneous or surgical intervention occurred in six patients; minor complications occurred in another six. Embolization occurred in five patients. Primary patency was 87% after 1 year, 83% after 2 years, and 78% after 4 years; secondary patency was 94%, 90%, and 88% at 1 year, 2 years, and 4 years, respectively. CONCLUSION: Primary stent placement should be the treatment of choice in unilateral chronic iliac artery occlusion. PMID- 7862974 TI - Abdominal aortic aneurysms: CT evaluation of renal artery involvement. AB - PURPOSE: To determine whether computed tomography (CT) assessment of the proximal extent of ruptured aneurysms can help the surgeon determine whether to initially clamp the pararenal aneurysm neck or the supraceliac aorta. MATERIALS AND METHODS: CT scans and medical records were reviewed and compared for 30 patients with ruptured abdominal aortic aneurysms (AAAs) who underwent immediate surgical repair. RESULTS: For 49 of 50 vessels in 25 patients, the authors correctly predicted at CT that AAAs originated caudal to the main renal artery origins. They also predicted that nine main renal arteries in five patients originated directly from the AAAs, but this was correct in only five arteries. Suprarenal clamping was required in all five patients. Infrarenal clamps were used before reconstruction in all 12 of the patients whose AAAs appeared to originate at least 30 mm below the main renal arteries. CONCLUSION: CT can help predict whether an initial aortic clamp can be placed caudal to the main renal artery orifices. Its use can be predicted with 100% certainty only when an aneurysm appears to originate at least 3 cm caudal to the origin of the main renal artery. PMID- 7862975 TI - Cost-effectiveness of MR angiography in cases of limb-threatening peripheral vascular disease. AB - PURPOSE: To evaluate the cost-effectiveness of magnetic resonance (MR) angiography in the preoperative planning of treatment in patients with limb threatening peripheral vascular disease (PVD). MATERIALS AND METHODS: A decision model was developed to study the effects of MR angiography on the outcome and cost of treatment. The authors calculated the incremental cost per quality adjusted life-years gained (ie, cost-effectiveness ratio) when conventional angiography was replaced or supplemented with MR angiography. Previously reported data regarding the accuracies of MR and conventional angiography were used in the analysis. RESULTS: The cost-effectiveness ratio of MR angiography ranged from negative (cost-reducing) values to $78,000. For the base case in which the sensitivity and specificity of MR angiography for the evaluation of inflow vessels were 92% and 88% and those of conventional angiography were 97% and 97%, respectively, the cost-effectiveness ratio was $25,895. CONCLUSION: MR angiography may be a cost-effective alternative to conventional angiography in patients with limb-threatening PVD if its accuracy for the inflow evaluation reaches certain thresholds. Further prospective investigation is warranted. PMID- 7862976 TI - Cardiac echo-planar MR imaging: comparison of single- and multiple-shot techniques. AB - PURPOSE: To compare the quality of cardiac images acquired with two-and four-shot echo-planar imaging (EPI) with that of images acquired with single-shot EPI. MATERIALS AND METHODS: Single-, two-, and four-shot EPI was performed to obtain axial images that traversed both cardiac ventricles. The subjects were 10 healthy men whose ages ranged from 22 to 38 years (mean, 27 years). The multiple-shot EPI data were acquired in snapshot (sequential) and cardiac-gated (non-sequential) modes. Image quality was compared by evaluation of the depiction of cardiac structures and analysis of signal intensity, contrast, and signal homogeneity. RESULTS: Multiple-shot EPI depicted the coronary and internal mammary arteries better than did single-shot EPI (P < .05). Intraventricular signal intensity was more homogeneous on multiple-shot images (P < .005). Cardiac-gated acquisition resulted in less image blurring and allowed acquisition of more phases per RR interval. CONCLUSION: Multiple-shot EPI rendered higher quality images than did single-shot EPI. PMID- 7862977 TI - Authentication of digital medical images with digital signature technology. AB - PURPOSE: To determine whether digital signature technology (DST) can authenticate digital medical images to the same level of authenticity required for interbank electronic transfer of funds. MATERIALS AND METHODS: Message digests were computed for two magnetic resonance images that differed only by the value of a single bit. RSA (Rivest, Shamir, and Adleman) public key cryptography was used to encrypt each message digest to form a digital signature for each image, a process analogous to the established use of RSA DST for electronic funds transfer. The process was then reversed to authenticate the original image from its digital signature. RESULTS: Although the images differed by less than 0.000095%, their message digests differed at 94% of their characters. The digital signature of the original image proved that it was authentic and that the altered image was not authentic. CONCLUSION: RSA DST can establish the authenticity of images to at least the level of confidence required for interbank electronic transfer of funds. PMID- 7862978 TI - Contrast material-carrying liposomes: biodistribution, clearance, and imaging characteristics. AB - PURPOSE: To assess the biodistribution, clearance, and computed tomographic (CT) imaging characteristics of interdigitation-fusion (IF) liposomes that carry iotrolan in their aqueous phases. MATERIALS AND METHODS: Biodistribution and clearance of liposomes containing iotrolan produced with the IF method (IF vesicles) were assessed in rats. CT scans of rats and dogs were obtained after injection of IF vesicles at 100 and 250 mg of iodine per kilogram of body weight. RESULTS: A high initial uptake (63%-96% of the injected dose) was found in the liver and spleen. Liver elimination showed half-lives to be 12.9 days at 250 mg of iodine per kilogram, 10.9 days at 100 mg, and 8.7 days at 25 mg. At 250 mg of iodine per kilogram, the rats had an average of 96 HU of hepatic and 321 HU of splenic enhancement. The dogs had 116 HU of hepatic and 65 HU of splenic enhancement. CONCLUSION: IF liposomes have favorable biodistribution, clearance, and imaging characteristics as hepatosplenic contrast agents. PMID- 7862979 TI - Adrenal gland enhancement at MR imaging with Mn-DPDP. AB - PURPOSE: To determine adrenal gland enhancement with manganese (II) N,N' dipyridoxylethylenediamine-N,N'-diacetate 5,5'bis(phosphate) (DPDP) at magnetic resonance imaging. MATERIALS AND METHODS: After phase III trials, fat-suppressed, motion-compensated, T1-weighted spin-echo images (repetition time, 500 msec; echo time, 12 msec) of 13 consecutive patients were obtained at 1.5 T at one site, prior to and approximately 30 minutes after intravenous administration of 5 mumol/kg Mn-DPDP. Images were analyzed visually and by means of region-of interest measurements, normalized to spleen. With data added from three more sites, enhancement of three adrenal adenomas and two metastases was analyzed. RESULTS: Twenty-five of 26 adrenal glands were depicted on MR images, and all showed enhancement. Mean adrenal enhancement (38%) was comparable to mean enhancement of liver (46%), pancreas (25%), and renal cortex (58%). Adrenal cortex and medulla could not be distinguished in nonenhanced or enhanced images. All three adrenal adenomas enhanced by more than 40%, but the metastases did not enhance. CONCLUSION: Functioning adrenal tissue (glands and at least some adenomas) are enhanced with Mn-DPDP. PMID- 7862980 TI - Acute flank pain: comparison of non-contrast-enhanced CT and intravenous urography. AB - PURPOSE: To compare non-contrast-enhanced computed tomography (CT) and intravenous urography (IVU) in the evaluation of patients who present with acute flank pain and in whom ureteric obstruction is suspected. MATERIALS AND METHODS: The findings at non-contrast-enhanced CT and IVU in 20 patients with acute flank pain were compared for the presence or absence of ureteric obstruction and delineation of ureteric stones. RESULTS: Twelve of the 20 patients had non contrast-enhanced CT and IVU findings consistent with ureteric obstruction. Of these 12 patients, five had a ureteric stone that was demonstrated on both non contrast-enhanced CT scans and IVU radiographs, six had a stone that was depicted on non-contrast-enhanced CT scans only, and in one patient a stone could not be delineated definitively on either non-contrast-enhanced CT scans or IVU radiographs. Eight patients had findings at non-contrast-enhanced CT and IVU consistent with the absence of obstruction. CONCLUSION: Non-contrast-enhanced CT is more effective than IVU in precisely identifying ureteric stones and is equally effective as IVU in the determination of the presence or absence of ureteric obstruction. PMID- 7862981 TI - Development of F-18-labeled fluoroerythronitroimidazole as a PET agent for imaging tumor hypoxia. AB - PURPOSE: To develop a hydrophilic ligand to image tumor hypoxia at positron emission tomography (PET). MATERIALS AND METHODS: Biodistribution of fluorine-18 labeled fluoroerythronitroimidazole (FETNIM) and F-18-labeled fluoromisonidazole (FMISO) was determined at PET and autoradiography in three mammary-tumor-bearing rats. The partition coefficient of FETNIM, FMISO, and misonidazole was determined. RESULTS: Biodistribution of F-18-labeled FETNIM at 1, 2, and 4 hours showed tumor-to-blood ratios of 2.29 +/- 0.599, 2.41 +/- 0.567 and 8.02 +/- 2.420, respectively, and tumor-to-muscle ratios of 0.66 +/- 0.267, 2.11 +/- 0.347, and 5.92 +/- 2.240, respectively. The tumor-to-blood count density ratio with F-18-labeled FETNIM at 4 hours after injection was significantly higher than with F-18-labeled FMISO. Autoradiographs indicated that both agents could help differentiate hypoxic versus necrotic region in the tumor. CONCLUSION: F-18 labeled FETNIM can help detect tumor hypoxia and is easier to prepare, less costly, and more hydrophilic than F-18-labeled FMISO. PMID- 7862982 TI - MR measurements of mesenteric venous flow: prospective evaluation in healthy volunteers and patients with suspected chronic mesenteric ischemia. AB - PURPOSE: To quantify portal vein (PV) and superior mesenteric vein (SMV) flow before and after a standardized meal in healthy volunteers and to prospectively evaluate patients with a clinical suspicion of chronic mesenteric ischemia on the basis of magnetic resonance (MR) measurement of flow in the mesenteric venous system in volunteers. MATERIALS AND METHODS: Cine phase-contrast flow measurements were acquired in 10 asymptomatic volunteers and in 10 patients. RESULTS: In volunteers, the difference between the fasting and post-prandial flows in the SMV and PV was significant (P < .001), with a peak flow augmentation of 245% +/- 74 and 70% +/- 29, respectively. Postprandial augmentation of peak flow in the SMV was significantly less in patients with mesenteric ischemia compared with volunteers (64% +/- 28; P = .02). SMV flow augmentation in patients without mesenteric ischemia did not differ significantly from that in volunteers (206% +/- 36; P = .31). CONCLUSION: Measurement of postprandial flow augmentation in the SMV with MR imaging shows promise as a noninvasive screening test for chronic mesenteric ischemia. PMID- 7862983 TI - Splanchnic blood flow in patients with cirrhosis and portal hypertension: investigation with duplex Doppler US. AB - PURPOSE: To investigate splanchnic blood flow changes in patients with hepatic cirrhosis and portal hypertension. MATERIALS AND METHODS: Duplex Doppler ultrasound (US) was used to measure blood flow in the superior mesenteric artery (SMA) and splenic artery in 20 patients with biopsy-proved cirrhosis and clinical evidence of portal hypertension, and in 20 healthy volunteers who were matched for age and sex. RESULTS: Mean SMA and splenic artery blood flow was significantly greater in the patients than in healthy subjects. Neither SMA nor splenic artery blood flow was increased in patients with normal-sized spleens; however, blood flow was significantly elevated in patients with splenomegaly. Total splanchnic blood flow in patients was also significantly elevated compared with healthy subjects. Total splanchnic blood flow in patients with normal-sized spleens was not significantly elevated compared with healthy subjects, but splanchnic flow was significantly increased in patients with splenomegaly. CONCLUSION: Blood flow is increased in the SMAs and splenic arteries of patients with cirrhosis and portal hypertension. Increased splanchnic blood flow associated with cirrhosis may occur exclusively in patients with splenomegaly. PMID- 7862984 TI - Posttraumatic intestinal stenosis: clinical and radiographic features in four patients. AB - PURPOSE: To characterize posttraumatic intestinal stenosis clinically and radiographically. MATERIALS AND METHODS: The clinical records and radiographic and pathologic findings were reviewed in four patients with posttraumatic stenosis. RESULTS: The patients experienced abdominal symptoms from 1 to 18 weeks after the trauma. While the small intestine was affected in two patients with ileus, the colon was involved in the other two patients with rectal bleeding or diarrhea. Barium studies showed an irregular contour within the severely narrowed intestine in three patients, even 25 weeks after the trauma. In these three patients, pathologic examinations of the resected specimens revealed a circumferential, open ulcer, whereas a scarred ulcer was present in the other patient. CONCLUSION: Posttraumatic intestinal stenosis is clinically characterized by a delayed onset of symptoms that differ according to the site of involvement. This condition should be included in the differential diagnosis of intestinal stenosis. PMID- 7862985 TI - Percutaneous gastrostomy and gastrojejunostomy: additional experience in 519 procedures. AB - PURPOSE: To assess the efficacy and safety of radiologically guided percutaneous placement of gastrostomy and gastrojejunostomy catheters. MATERIALS AND METHODS: Over 6 years, 562 referred patients were considered for gastrojejunostomy or gastrostomy procedures. In 43 cases (7.7%), the procedure was not performed because of overlying viscera, high position of the stomach, or massive ascites. In 478 patients, 519 procedures were performed. RESULTS: Of 507 attempted gastrojejunostomy procedures, 482 (95.1%) were successful, 14 (2.8%) catheters could not be advanced through the pylorus and necessitated gastrostomies, and 11 (2.2%) were technical failures. Twelve gastrostomy tubes were placed for decompression, with a 100% success rate. Thirty-day follow-up data were available for 457 procedures: The 30-day mortality rate was 17.1% (71 of 416 patients). There were two gastrostomy-related deaths. The overall major and minor complication rates were 1.3% and 2.9%, respectively. CONCLUSION: Percutaneous gastrostomy and gastrojejunostomy are safe and effective methods of providing short- or long-term enteral nutrition or upper gastrointestinal tract decompression. PMID- 7862986 TI - Effusion criteria and clinical importance of glenohumeral joint fluid: MR imaging evaluation. AB - PURPOSE: To investigate the clinical importance of glenohumeral joint (GHJ) fluid. MATERIALS AND METHODS: The amount of GHJ fluid in 17 volunteers and 208 consecutive patients was graded at magnetic resonance imaging with T2-weighted fat-suppressed coronal oblique images by two blinded observers. Thorough historical data and physical examination results were available for 108 patients. Presence and grade of GHJ fluid were correlated with age, sex, presence of osteophytes activity scale, supraspinatus tenderness, clinical impingement, prior subacromial injections, rotator cuff tears (RCTs), joint tenderness, joint pain, and history of trauma. RESULTS: GHJ fluid was seen in 40% (n = 83) of patients and in only 6% (n = 1) of volunteers. The volume of fluid correlated with osteophytes (P = .04), increasing age (P = .0001), and RCTs (P = .005). No correlation was found with activity rating, focal tenderness, joint pain, diagnosis of impingement, impingement grade, supraspinatus insertional tenderness, subacromial injection, prior trauma, or sex. CONCLUSION: The presence of GHJ fluid appears to be abnormal and in most cases is related to RCTs and osteoarthritis. It seems to be unrelated to activity, tenderness, or impingement. PMID- 7862987 TI - Medial collateral ligament injuries: evaluation of multiple signs, prevalence and location of associated bone bruises, and assessment with MR imaging. AB - PURPOSE: To investigate the multiple signs of medial collateral ligament (MCL) sprains, including the location and prevalence of associated bone bruises, and evaluate the accuracy of the criteria proposed for magnetic resonance (MR) imaging in grading these sprains. MATERIALS AND METHODS: MR images were evaluated for signs of MCL injury in 76 patients with MCL sprains and 25 asymptomatic volunteers. These signs were then correlated with standards used to determine MCL injury at clinical evaluation. The grade of MCL injury as determined with MR imaging criteria was compared with clinical findings. RESULTS: All signs demonstrated little interobserver variability and were specific. The most sensitive signs were fascial edema and loss of demarcation from adjacent fat. This MR imaging grading system was inaccurate for classification of grade 3 MCL tears and was only questionably accurate for grades 1 and 2. CONCLUSION: Multiple signs of MCL sprains on MR images have varying sensitivities. MR grading systems may not be accurate for classification of MCL injuries. PMID- 7862988 TI - Rotator cuff disorders: interobserver and intraobserver variation in diagnosis with MR imaging. AB - PURPOSE: To determine interobserver and intraobserver variation in the interpretation of magnetic resonance (MR) images in rotator cuff disorders. MATERIALS AND METHODS: MR images of the shoulder in 97 patients were retrospectively reviewed twice, with a 3-week interval. Surgical findings indicated a full-thickness tear in 29 patients, grade 1 impingement in 19 (tendinitis), and grade 2 impingement (partial tear) in 26. The control population comprised 23 asymptomatic volunteers or patients. RESULTS: All observers were accurate in the diagnosis of a full-thickness tear (89%-98%), with good intraobserver (kappa = 0.67-0.84) and interobserver agreement (kappa = 0.74 0.92). In diagnoses of tendinitis, partial tear, and normal cuff, there were wide ranges of sensitivity (13%-74%) and specificity (72%-93%), as well as poor interobserver (kappa = 0.12-0.60) and intraobserver agreement (kappa = 0.35 0.78). CONCLUSION: Full-thickness tears of the rotator cuff can be accurately identified at MR imaging with little observer variation. Consistent differentiation of normal rotator cuff, tendinitis, and partial thickness tears is more difficult. PMID- 7862989 TI - Skeletal muscle contraction in healthy volunteers: assessment with Doppler tissue imaging. AB - PURPOSE: To evaluate Doppler tissue imaging (DTI) in the measurement and characterization of skeletal muscle movement and contraction. MATERIALS AND METHODS: Five healthy male subjects were examined with a commercially available ultrasound imaging unit modified for DTI. Velocities of the rectus femoris and gastrocnemius-soleus muscle motion were measured during the patellar and ankle reflexes, respectively. Velocity profiles were analyzed after digitization of the DTI images. Time to peak velocity, velocity range, and relaxation time were examined in each case over three contractions. For reflex contractions, reproducibility was examined by determining the latency period, area under the velocity curve, and duration of contraction for each of five consecutive reflexes. RESULTS: Isotonic muscle contraction could be distinguished from passive movement by a higher tissue velocity range, by a more rapid initial acceleration slope, and by the velocity differential across the muscle. The intensity and duration of the contraction and plateau and relaxation phases of isotonic contraction could be measured in all muscle groups. CONCLUSION: DTI provides detailed information about the dynamics of skeletal muscle contraction. PMID- 7862990 TI - Laparoscopic gray-scale and color Doppler US: preliminary animal and clinical studies. AB - PURPOSE: To evaluate a semiflexible ultrasound (US) transducer inserted through a laparoscopic port to image abdominal structures. MATERIALS AND METHODS: Laparoscopic US with a 9.6-mm-diameter, 5.0-7.5-MHz semiflexible transducer with gray-scale, color, and spectral Doppler capabilities was performed in three miniature swine and in 25 patients with a variety of abdominal abnormalities. RESULTS: This miniature US probe was used to locate normal structures such as blood vessels, allowing the surgeon to decide the best approach for dissection. Color and spectral Doppler US proved especially useful in differentiating vascular from nonvascular structures. The presence or absence of stones in the gallbladder and common bile duct was readily determined. It was possible to detect masses and to provide guidance for their aspiration or biopsy within abdominal organs. In 10 cases (40%), laparoscopic US helped the surgeon make the decision for clinical management and altered the surgical procedures. CONCLUSION: Laparoscopic US was useful in assisting laparoscopic evaluation of abnormalities in the abdomen. PMID- 7862991 TI - Breast cancer diagnosis in women with subglandular silicone gel-filled augmentation implants. AB - PURPOSE: To determine whether breast augmentation implants interfere with detection of breast cancer and to characterize the projections that offer an improvement in the detection of disease. MATERIALS AND METHODS: The mammographic examinations, clinical presentation, and pathologic findings were retrospectively reviewed in 18 patients who underwent breast augmentation with silicone gel filled implants. RESULTS: At diagnosis, 16 patients (89%) had palpable abnormalities. Standard mammographic views were negative in 17 patients (94%). Modified implant compression views (used with implant displacement) showed abnormalities in 12 patients (67%). Sixteen (89%) of the 18 patients had invasive carcinomas, and seven (39%) had positive axillary lymph nodes. CONCLUSION: Standard mammographic views are inadequate for breast cancer screening in patients with silicone gel-filled implants. Although additional modified compression views offer a moderate improvement in breast cancer detection, imaging with tangential mammographic views, sonography of palpable areas, and breast physical examination in conjunction with mammography will offer additional benefit in breast cancer detection. PMID- 7862992 TI - Seromas in residual fibrous capsules after explantation: mammographic and sonographic appearances. AB - PURPOSE: To evaluate the mammographic and sonographic findings associated with seromas that develop in residual fibrous capsules after explantation of breast prostheses. MATERIALS AND METHODS: Preoperative and postoperative mammograms were reviewed in 86 patients (mean age, 51 years; age range, 24-71 years) who had undergone surgical explantation of breast prostheses. Six seromas were found in four patients 46-68 years of age. Imaging findings were correlated with surgical and laboratory results for three seromas. A presumptive diagnosis was made of the other three lesions. RESULTS: Mammograms demonstrated all seromas as large, elliptic, water-opacity masses, some with well-circumscribed and some with irregular borders. Sonograms showed thin, compressible masses, two of which were flat and anechoic and one of which was hypoechoic. Three patients' images were initially misinterpreted, leading to excision of two seromas and aspiration of one. Seromas were not identified in patients whose implants were removed by means of complete capsulectomy. CONCLUSION: Radiologists must be aware of the imaging findings associated with seromas and of a patient's surgical history to avoid biopsy of benign lesions. PMID- 7862993 TI - Diffuse pleural thickening: percutaneous CT-guided cutting needle biopsy. AB - PURPOSE: To assess the diagnostic yield of computed tomography (CT)-guided percutaneous cutting needle biopsy of diffuse pleural thickening. MATERIALS AND METHODS: In 42 consecutive adult patients with diffuse pleural disease seen, 45 CT-guided percutaneous biopsies were performed with an 18-gauge cutting needle powered by a hand-held, spring-operated biopsy instrument. Results were assessed retrospectively. RESULTS: Sufficient pleural tissue for histologic diagnosis was obtained in 42 of the 45 biopsies, with a correct histologic diagnosis made in 39 of the 42 specimens. Specificity and sensitivity for helping differentiate malignant from benign disease were 100% and 83%, respectively. Positive and negative predictive values were 1.0 and 0.60, respectively. By combining findings at biopsy and at CT (presence or absence of pleural thickness greater than 1 cm, mediastinal-circumferential involvement, irregular contour), sensitivity and negative predictive values reached 100% and 1.0, respectively. CONCLUSION: Combined findings of CT-guided percutaneous cutting needle biopsy and CT are useful in first-line investigation of diffuse pleural thickening. PMID- 7862994 TI - Stenosis of the central airways: evaluation by using helical CT with multiplanar reconstructions. AB - PURPOSE: To assess the accuracy of helical computed tomography (CT) with multiplanar reconstructions (MPRs) in the evaluation of stenoses of the central airways. MATERIALS AND METHODS: Thin-section axial CT and helical CT with MPRs were used to examine the central tracheobronchial tree for the presence of stenosis in 27 patients who underwent lung transplantation and 17 nontransplantation patients. The findings from these modalities were then compared with the findings obtained at conventional tomography and bronchoscopy, when available. RESULTS: Axial CT alone was 91% accurate in depicting stenosis, CT with MPRs was 94% accurate, and conventional tomography was 89% accurate in the evaluation of bronchial anastomosis in transplant recipients. CT and CT scans with MPRs were each 91% accurate in depicting stenosis in nontransplantation patients; the single false-negative finding showed focal tracheomalacia at bronchoscopy. CONCLUSION: CT with MPRs may be more accurate than thin-section axial CT in the demonstration of mild stenosis, the length of a stenosis, and horizontal webs. PMID- 7862995 TI - Diaphragmatic motion: fast gradient-recalled-echo MR imaging in healthy subjects. AB - PURPOSE: To investigate the feasibility of imaging diaphragmatic motion with a fast gradient-recalled-echo (GRE) magnetic resonance (MR) pulse sequence. MATERIALS AND METHODS: Fast GRE pulse sequences in sagittal and coronal planes were used to acquire repeated, single-level, 1.2-second scans in 10 healthy volunteers during deliberately slowed, approximate-vital-capacity breathing. Motion was analyzed subjectively by viewing the image sequences as cine loops and quantitatively by measuring the displacement of different points on the diaphragm at a workstation. RESULTS: Temporal and spatial resolutions were adequate in all subjects. Absolute excursion of the domes was 4.4 cm on the right and 4.2 cm on the left. Analysis of diaphragmatic displacement at different locations revealed a gradient of excursion that increased from anterior to middle to posterior (P < .05-.001; paired t test). Excursion of the lateral aspects was greater than that of the medial aspect (P < .001). CONCLUSION: Fast GRE MR imaging can be reliably used to demonstrate diaphragmatic motion and may prove useful in the investigation of normal and abnormal respiratory mechanics. PMID- 7862996 TI - Diaphragmatic rupture: CT findings in 11 patients. AB - PURPOSE: To determine the signs of diaphragmatic rupture at computed tomography (CT) and the frequency of preoperative diagnosis with CT. MATERIALS AND METHODS: CT scans in 11 consecutive patients with surgically proved tears of the diaphragm due to blunt trauma were reviewed by two chest radiologists. The observers assessed the presence of discontinuity of the diaphragm, herniation of abdominal viscera or omentum, and waistlike constriction of the herniated stomach or bowel (collar sign). Hospital records were reviewed to confirm surgical findings and ascertain whether the diagnosis has been suggested at CT. RESULTS: In eight of 11 patients, rupture of the diaphragm was on the left, and in three it was on the right. In nine patients, diagnostic findings were identified retrospectively on CT scans; these included discontinuity of the diaphragm (n = 9), herniation of the abdominal organs or bowel (n = 7), and constriction of the stomach (n = 3). CONCLUSION: CT enables detection of most diaphragmatic tears due to blunt trauma. PMID- 7862997 TI - Artificial neural network for diagnosis of acute pulmonary embolism: effect of case and observer selection. AB - PURPOSE: To compare the diagnostic performance of an artificial neural network (ANN) with that of physicians in patients with suspected pulmonary embolism (PE). MATERIALS AND METHODS: An ANN was developed to predict PE by using findings from ventilation-perfusion lung scans and chest radiographs. First, the network was evaluated on 1,064 cases from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study that had a definitive angiographic outcome. An upper and lower bound of its diagnostic performance was provided depending on case difficulty. Then, the network was tested on 104 patients with suspected PE in whom pulmonary angiography was essential for diagnosis. The diagnostic performance of the ANN was compared with that of (a) two nuclear medicine physicians who read the scans for the needs of this study and (b) the nuclear medicine physicians who originally read the scans. The effects of case and observer selection on performance were addressed. RESULTS: The ANN outperformed the physicians when they used the PIOPED criteria for categoric assessment, and it performed as well as the two study physicians on the basis of their probability assessments. CONCLUSION: The ANN can detect or exclude PE in a highly selected group of difficult cases with a consistency equivalent to that of very experienced physicians. PMID- 7862998 TI - Mechanism of satisfaction of search: eye position recordings in the reading of chest radiographs. AB - PURPOSE: To use the eye position recordings of observers as they read chest images to advance understanding of the mechanism of "satisfaction of search," a phenomenon in which the detection of one abnormality interferes with the detection of other abnormalities. MATERIALS AND METHODS: Eight radiologists examined chest images that contained simulated pulmonary nodules and native abnormalities. Accuracy in detecting nodules and native abnormalities and eye position, gaze duration, and total search time were recorded. RESULTS: Nodule detectability was lower on native abnormality-containing images than it was on normal images (P < .005). Native-abnormality detectability was not negatively affected by the nodules. Most missed nodules were fixated; only those on images without native abnormalities, however, received prolonged visual attention. CONCLUSION: The satisfaction of search phenomenon is an important source of error in the detection of subtle abnormalities but not of obvious abnormalities. Obvious abnormalities capture visual attention and decrease vigilance for more subtle abnormalities. PMID- 7862999 TI - Lower extremity spiral CT angiography versus catheter angiography. AB - Both catheter and spiral computed tomography (CT) angiography of the lower extremity vasculature were performed in six patients with clinically symptomatic peripheral vascular disease. Forty-eight arteries were studied and were independently evaluated for arterial stenoses and occlusions. Compared with catheter arteriography, CT angiography correctly depicted segmental occlusions and significant stenoses (> 50%) in 26 of 28 arteries, yielding a sensitivity of 92.9%, a specificity of 96.2%, and an overall accuracy of 95.5%. PMID- 7863000 TI - Improved MR venography: use of fast short inversion time inversion-recovery technique in evaluation of venous angiomas. AB - Eleven patients (five female and six male, aged 6-67 years) with venous angiomas underwent axial and coronal T1-weighted and fast short inversion time inversion recovery (STIR) magnetic resonance (MR) imaging to assess the full extent of the malformations. Images were assessed subjectively by the authors in a nonblinded study. In all patients, fast STIR images depicted more anatomic detail than did T1-weighted images and depicted venous angiomas more clearly than did contrast material-enhanced CT scans but did not help discrimination of arteries and veins. PMID- 7863001 TI - Management of probably benign breast lesions. PMID- 7863002 TI - Recurrent miliary sarcoidosis after lung transplantation. PMID- 7863003 TI - Stability of malignant breast calcifications. PMID- 7863004 TI - The prosomes (multicatalytic proteinases; proteasomes) and their relationship to the untranslated messenger ribonucleoproteins, the cytoskeleton, and cell differentiation. PMID- 7863005 TI - Molecular properties and regulation of G-protein-coupled receptors. PMID- 7863006 TI - The human immunodeficiency virus type-1 long terminal repeat and its role in gene expression. PMID- 7863007 TI - Processing of eukaryotic ribosomal RNA. AB - In summary, it can be argued that the understanding of eukaryotic rRNA processing is no less important than the understanding of mRNA maturation, since the capacity of a cell to carry out protein synthesis is controlled, in part, by the abundance of ribosomes. Processing of pre-rRNA is highly regulated, involving many cellular components acting either alone or as part of a complex. Some of these components are directly involved in the modification and cleavage of the precursor rRNA, while others direct the packaging of the rRNA into ribosome subunits. As is the case for pre-mRNA processing, snoRNPs are clearly involved in eukaryotic rRNA processing, and have been proposed to assemble with other proteins into at least one complex called a "processosome" (17), which carries out the ordered processing of the pre-rRNA and its assembly into ribosomes. The formation of a processing complex clearly makes possible the regulation required to coordinate the abundance of ribosomes with the physiological and developmental changes of a cell. It may be that eukaryotic rRNA processing is even more complex than pre-mRNA maturation, since pre-rRNA undergoes extensive nucleotide modification and is assembled into a complex structure called the ribosome. Undoubtedly, features of the eukaryotic rRNA-processing pathway have been conserved evolutionarily, and the genetic approach available in yeast research (6) should provide considerable knowledge that will be useful for other investigators working with higher eukaryotic systems. Interestingly, it was originally hoped that the extensive work and understanding of bacterial ribosome formation would provide a useful paradigm for the process in eukaryotes. However, although general features of ribosome structure and function are highly conserved between bacterial and eukaryotic systems, the basic strategy in ribosome biogenesis seems to be, for the most part, distinctly different. Thus, the detailed molecular mechanisms for rRNA processing in each kingdom will have to be independently deciphered in order to elucidate the features and regulation of this important process for cell survival. PMID- 7863008 TI - Adenylyl cyclases: a heterogeneous class of ATP-utilizing enzymes. PMID- 7863009 TI - Mutational spectrometry: means and ends. PMID- 7863010 TI - Interaction of epidermal growth factor with its receptor. PMID- 7863011 TI - Biological implications of the mechanism of action of human DNA (cytosine 5)methyltransferase. PMID- 7863012 TI - The anxiolytic SC 48274 (AGN 2979; BTG 1501) in generalized anxiety disorder. PMID- 7863013 TI - GABA-transaminase in brain and blood platelets: basic and clinical aspects. AB - Several lines of evidence suggest that the major inhibitory neuro-transmitter, gamma-aminobutyric acid (GABA) is involved, both directly and indirectly, in the pathogenesis of certain neurological and psychiatric disorders. The main enzyme responsible for GABA catabolism is gamma-aminobutyrate aminotransferase (GABA-T). Inhibition of this enzyme produces a considerable elevation of brain GABA concentrations, and such elevation has been correlated with many pharmacological effects. There seems to be that, as is discussed below, GABA-T activity in the brain and/or blood platelets is related to some neuro-psychiatric disorders such as alcoholism, epilepsy and Alzheimer's disease. GABA-T has been identified in the blood platelets with similar characteristics to those of brain GABA-T. In this way, studies on GABA-T activity in neuro-psychiatric disorders could be performed to understand, diagnosis and treat GABA-related disorders of the central nervous system (CNS). PMID- 7863014 TI - On the significance of cholecystokinin receptors in panic disorder. AB - Interest in the biological aspects of panic disorder has been focussed mainly on the noradrenergic and serotonergic systems in the brain. Recently evidence has been found that Cholecystokinin (CCK) receptors in the Central Nervous System (CNS) may be involved in panic disorders. This hypothesis is based on the results of animal electrophysiological studies, animal models of anxiety and on challenge test using CCK fragments in humans. In this review, the studies evaluating the putative involvement of CCK, and especially CCK-B receptors, in panic disorder will be discussed. PMID- 7863015 TI - Simple reaction time event-related potentials: effects of alcohol and diazepam. AB - Acute effects of alcohol and diazepam on reaction time (RT) and event-related potential (ERP) measures were examined in 108 healthy male volunteers. The subjects engaged in a simple RT task at two levels of stimulus intensity during baseline and treatment sessions. Lower stimulus intensity produced increased RT's, increased ERP peak latencies, and suppression of peak amplitudes. Moderate and high doses of alcohol, and high doses of diazepam produced increased RT's. Alcohol suppressed P100 and N100 amplitudes, while diazepam suppressed P100 amplitudes only. P100 amplitudes were correlated to RT's under baseline and treatment conditions. These results were taken as evidence for impaired stimulus detection during alcohol and diazepam intoxication, with both drugs influencing sensory-perceptual processes and alcohol alone influencing the degree of attentiveness. PMID- 7863016 TI - Adrenocorticotropic hormone, beta-endorphin and cortisol responses to oCRH in unipolar depressed patients pretreated with dexamethasone. AB - 1. Corticotropin-releasing hormone (ovine CRH, 100 micrograms intravenous bolus) was given to 63 unipolar depressed inpatients following the 1 mg overnight dexamethasone suppression test (DST). The depressed patients included 18 minor, 24 simple major and 21 melancholic subtypes. 2. Baseline or postdexamethasone plasma levels of intact adrenocorticotropic hormone (ACTH), beta-endorphin/beta lipotropin (beta END/beta LPH), cortisol, and dexamethasone were measured, as well as the post DST+CRH hormone responses. 3. CRH administration 9.5 hr after dexamethasone resulted in a significant enhancement of ACTH, beta END/beta LPH and cortisol secretion. The post DST+CRH ACTH and beta END/beta LPH- but not cortisol-values exceeded their baseline hormone levels. The post DST+CRH ACTH- but not beta END/beta LPH or cortisol-levels were significantly higher in major depressives compared to minor depressives. The post DST+CRH ACTH and beta END/beta LPH--but not cortisol-levels were significantly higher in DST nonsuppressors than suppressors. The post DST+CRH ACTH levels were significantly and positively related to severity of illness. 4. The results provide evidence that the pathophysiology underlying the abnormal DST+CRH and DST tests in melancholia is localized at the pituitary level and may consist of a CRH-driven breakthrough of corticotropic cell secretion synergized by central and peripheral agents, in conjunction with a decrease in glucocorticoid feedback suppressibility. PMID- 7863017 TI - Selective inhibition by alcohol and cortisol of natural killer cell activity of lymphocytes from cord blood. AB - 1. The immunosuppressive effects of drugs such as alcohol or hormones such as cortisol may be age-related. To test this hypothesis, the authors investigated the in vitro effects of ethanol (EtOH) and cortisol on Natural Killer (NK) cell activity of lymphocytes from normal cord blood in comparison with that of lymphocytes from normal adult peripheral blood. 2. K562, an erythroleukemia cell line, was used as a target in a 4 hr 51Cr release assay. 3. Ethanol at 0.3% (V/V) and cortisol at 0.05, 0.1 and 0.2 microgram/ml concentrations, added directly to a mixture of effector and target cells significantly suppressed the NK activity of cord blood lymphocytes in a dose dependent fashion, whereas similar concentrations of either EtOH or cortisol did not manifest significant immunoregulatory effects on NK cell activity of normal adult lymphocytes. 4. Pre treatment of the target with either EtOH or cortisol for 4 hours did not affect cytotoxicity. Inhibition of cytotoxicity was also not due to direct toxicity of effector cells because lymphocytes treated with either EtOH or cortisol showed normal 51Cr release and their viability was comparable to that of untreated control cells. 5. This suggests a selective inhibitory effect of EtOH and cortisol on NK activity of neonatal lymphocytes that may be of clinical significance. PMID- 7863018 TI - Reduced P3 amplitudes are associated with both a family history of alcoholism and antisocial personality disorder. AB - 1. Previous research has demonstrated that the amplitude of the P3 component of the event-related electroencephalographic potential (ERP) is influenced by the presence/absence of a family history of alcoholism (FHA). The present study extended this line of research by examining the P3 effects of both FHA and antisocial personality disorder (ASP) in a 2 x 2 factorial design. 2. The task required subjects to judge the orientation of an infrequently-occurring outline drawing, representing an aerial view of a human head. 3. Analyses of P3 amplitudes elicited by this drawing revealed reductions attributable to the effects of both FHA and ASP, but not their interaction. These effects were most apparent at frontal electrode sites. Analyses of P3 latency revealed no consistent pattern of findings. However, the interval between P3 and manual reaction time was shorter in the ASP+ group relative to the ASP-group. PMID- 7863019 TI - Do enzyme inducers modify haloperidol decanoate rate of release? AB - 1. Plasma levels were monitored for about 18 months during therapy with haloperidol decanoate. When steady-state was reached, patients treated without enzyme inducers showed in their plasma concentrations a stable plateau and a very low fluctuation. Furthermore, doses were correlated to plasma levels (r = 0.9). 2. Contrary, patients treated with both haloperidol decanoate and enzyme inducers seemed to present in their plasma concentration a very large fluctuation with C min (plasma concentrations measured just before the injection) significantly lower than those of the other group. Moreover their C min values were excluded from the linear regression curve calculated between plasma levels and doses in patients without enzyme inducers. 3. Our data suggest a shortening of the absorption half-time of haloperidol. In this case, it seems necessary to diminish the interval between injections than to give higher dosage in order to maintain plasma concentrations. PMID- 7863020 TI - The effect of corticosterone in rats submitted to the elevated plus-maze and to to pentylenetetrazol-induced convulsions. AB - 1. In order to examine the effects of corticosterone in the anxiety response, the effect of acute, subchronic and chronic corticosterone (CORT) administration were studied using two animal models to study anxiolytic effects of drugs: the elevated plus-maze and the blockade of pentylenetetrazol (PTZ)-induced clonic convulsion. 2. The results obtained with the plus-maze showed an increase in the percentage of open arm entries and time spent in the open arms after acute treatment with the CORT. These results may be interpreted as an anxiolytic effect of corticosterone. Three days of vehicle treatment followed by an acute CORT administration, produced results that should also indicate anxiolytic effect of the corticosteroid. No effect was seen after 14 days of vehicle treatment followed by an acute CORT injection. Subchronic or chronic CORT treatment did not produce results different from controls. CORT treatment did not affect the PTZ induced clonic convulsion. 3. In conclusion these results suggest that the acute anxiolytic effect observed in the elevated plus-maze did not occur after repeated CORT administration or mild stressors. Moreover they also suggest that the anxiolytic effect did not involve GABA mechanisms. PMID- 7863021 TI - Different effects of antidepressants on dissociation of 3H-imipramine from solubilized binding sites of rat brain. AB - 1. The effects of several antidepressants and 5-hydroxytryptamine on dissociation of 3H-imipramine from solubilized binding sites were investigated. 2. Binding sites were solubilized from rat brain membranes and gelfiltrated on a column of Sephacryl S-300. 3. Most of the agents used allowed biphasic dissociation with 1mM of displacing agent and without using dilution-induced dissociation. This biphasic dissociation without nonspecific effects of membranes may be due to the existence of low-affinity binding sites. 4. Dissociation of up to 40 min followed first-order kinetics. The dissociation half-life of 3H-imipramine with the various displacing agents was calculated at from 15.0 to 25.0 min, and the differences among the agents were not so significant as the attenuation or the acceleration of the dissociation was indicated. The lower concentration of the displacing agents may obscure the modulation of the dissociation. PMID- 7863022 TI - Effect of iohexol on pulmonary arterial pressure at pulmonary angiography in patients with pulmonary hypertension. AB - The effects of 300 mgI/ml of iohexol on pulmonary arterial pressure at selective pulmonary angiography were evaluated in seven patients with pulmonary hypertension due to pulmonary thromboembolism. The total number of contrast injections was 26. Pulmonary arterial pressure was recorded before and after each injection. The effect of iohexol on pulmonary arterial pressure in the pulmonary hypertensive circulation was slight. The results suggest that iohexol at 300 mgI/ml may be safe as a contrast medium for selective pulmonary angiography in patients with pulmonary hypertension. PMID- 7863023 TI - Real-time high resolution ultrasonography of solid breast masses: use of a 10-MHz mechanical sector transducer with a water bag. AB - We evaluated the diagnostic accuracy of real-time high-resolution ultrasonography (RHUS) for solid breast masses, using a 10-MHz mechanical sector transducer with a water bag. A total of 103 breast nodules in 100 women were analyzed. The nodules consisted of 42 carcinomas, 10 fibroadenomas, 38 mastopathies, and 13 miscellaneous lesions. Of them, 72.8% were less than 2 cm in size. Diagnostic accuracy was correlated with the size and pathology of the nodules. Sensitivity, specificity, and accuracy were 95.2%, 83.6%, and 88.3% for carcinomas, 90.0%, 88.2%, and 88.3% for fibroadenomas, and 50.0%, 98.5%, and 80.6% for mastopathies, respectively. The overall rate of diagnostic accuracy was 74.8%. The rate of accuracy according to mass size were 87.3% (-1 cm), 87.2% (1-2 cm), 88.0% (2-5 cm) and 100% (5 cm-). False positive cases (n = 10) included seven mastopathies, two granulomas, and one fibroadenoma. False negative cases (n = 2) included one fibroadenoma and one abscess. RHUS, using a 10-MHz mechanical sector transducer, was an excellent method for the diagnosis of solid breast masses. PMID- 7863024 TI - Non-T1-weighted spin-echo MR imaging with contrast material: experimental and preliminary clinical assessment. AB - To clarify the role of contrast-enhanced non-T1-weighted spin-echo (SE) MR imaging, phantom experiments and 20 clinical examinations were conducted. All of the SE pulse sequences demonstrated enhancement on gadopentetate dimeglumine solution phantoms. Enhancement effect was also observed on proton density weighted and T2-weighted images in tumors. This property might be better recognized and utilized in selecting pulse sequences in routine MR examinations. PMID- 7863025 TI - Flow velocity and volume measurement of superior and inferior mesenteric artery with cine phase contrast magnetic resonance imaging. AB - The flow velocity and volume of the superior and inferior mesenteric arteries (SMA, IMA) were measured with cine phase contrast magnetic resonance (MR) imaging in five healthy volunteers. Each volunteer was first measured in a fasting state, and then one, two, and three hours after a meal. The average SMA flow volume of the volunteers was 230.3 +/- 46.8 ml/min (mean +/- standard error) during the fasting state, and 714.7 +/- 207.7 ml/min, 339.2 +/- 85.7 ml/min, and 263.8 +/- 21.0 ml/min, respectively, at one, two, and three hours postmeal. The increase at one hour postmeal was statistically significant (p < 0.05). The corresponding flow measurements in the IMA were 63.1 +/- 11.2 ml/min, 67.6 +/- 11.2 ml/min, 57.9 +/- 8.6 ml/min, and 53.2 +/- 6.8 ml/min. These values do not represent a statistically significant flow volume change in the IMA. In all volunteers, the SMA volumetric flow increased the most one hour after the food challenge (72-400% relative to baseline). Diastolic velocity in the SMA increased significantly one hour postmeal, but systolic velocity did not change significantly. The IMA did not demonstrate a significant change in either systolic or diastolic velocity. The difference between the SMA and IMA in the way of reacting against the food challenge is thought to represent the difference between the requirements of small and large intestine for blood supply after the food challenge. These data demonstrate the possibility of this modality for the assessment of conditions such as chronic mesenteric ischemia. PMID- 7863026 TI - Peritoneal implants without ascites: preoperative CT diagnosis in colon carcinoma patients. AB - We evaluated the preoperative CT findings in 10 patients with colon carcinoma in whom peritoneal metastases had been surgically confirmed. Seven patients lacked ascites. No CT findings suggestive of peritoneal metastasis were observed in two patients without ascites even by retrospective evaluation. A large mass was observed in the cul-de-sac in another. In the remaining four patients, small peritoneal metastases ranging from 8 to 11 mm in diameter were observed at the omentum in two, along the falciform ligament in one, and at both the omentum and the iliac fossa in one; three of these patients had received no prospective diagnosis of peritoneal metastasis prior to the surgery. In patients with advanced colon carcinoma with suspected serosal invasion, the entire peritoneal cavity should be carefully examined and interpreted using CT in order to detect small peritoneal implants even when ascites is absent. PMID- 7863027 TI - SPECT measurements of cerebral blood volume before and after acetazolamide in occlusive cerebrovascular diseases. AB - Cerebral blood volume before and after acetazolamide was measured by SPECT to evaluate cerebral vasodilatory capacity in eight patients with cerebrovascular disease and five control subjects. Two SPECT measurements were performed serially, and acetazolamide was administered between them. The ratio of increase in hemispheric blood volume was calculated, and it was compared with the results of cerebral blood flow and cerebral blood volume measurements. A cerebral vasodilatory capacity map, the image after acetazolamide minus the baseline image, was also produced. Acetazolamide increased hemispheric blood volume in all unilateral carotid disease than in the uninvolved hemispheres of the patients and control subjects. The ratio of concordance with blood flow and blood volume measurements was approximated at 80%. Cerebral vasodilatory capacity mapping revealed three defects compatible with the clinical data. SPECT measurements of cerebral blood volume after acetazolamide can be performed following baseline SPECT with no additional radiotracer, and may be helpful to assess hemodynamic status. PMID- 7863028 TI - Hyperthermia for bone and soft tissue sarcoma: relationship between computerized tomographic and histological findings. AB - Between 1983 and 1992, 38 patients with 44 tumors of bone and soft tissue sarcoma were treated by hyperthermia combined with radiotherapy or chemotherapy. The overall response rate in this series was 48% (21/44). The average time for heating to 42 degrees C and the average maximum temperature did not correlate with the local effect. The percentage of the low density area on CT images and the average maximum temperature were well correlated. When 100% necrosis was evaluated as CR and up to 50% necrosis as PR, the local response rate was elevated from 42% to > 65%. Bone and soft tissue sarcomas are good targets for hyperthermia combined with radiotherapy and chemotherapy. Some tumors indicated for this study were too large to heat with the present heating apparatus. Percent low density and percent necrosis were correlated to some degree, but adoption of this phenomenon as a criterion for evaluation should be considered carefully. PMID- 7863029 TI - Thallium-201 single photon emission computed tomography in the evaluation of thymic carcinoma. AB - Thymic carcinoma is a rare mediastinal tumor that is distinguished from malignant thymoma without cytologic atypia. We present two cases of thymic carcinoma with high uptake of Tl-201. Absence of Tl-201 uptake in a residual mass on the CT scan indicated a lack of tumor viability after the completion of therapy, which was verified by sequential needle biopsy. Tl-201 SPECT seems to be useful both in detecting thymic carcinoma and in assessing the therapeutic effect. PMID- 7863030 TI - Lymphangioma of the mesentery and small intestine: a case report showing a solid tumor with a cystic component on US and CT. AB - We encountered a patient with multiple lymphangiomas of the mesentery and small intestine. Ultrasonography and computed tomography showed a mesenteric tumor composed of a solid component with a small cystic part. This unusual appearance made the differential diagnosis between lymphangioma and other intra-abdominal solid tumors difficult. PMID- 7863031 TI - Localized reduction in 123I-MIBG accumulation in the lung. AB - A patient with old myocardial infarction underwent 123I-MIBG scintigraphy to evaluate the adrenergic nerve system in the heart following the treatment of pneumonia. Decreased accumulation of MIBG was observed in the right lower lung field, corresponding to the area affected by pneumonia, as well as in the left ventricle with myocardial infarction. 99mTc-MAA lung perfusion scan demonstrated hypoperfusion in the region of reduced MIBG uptake. Regional decrease in MIBG uptake in the lung is considered to suggest lung pathology, and lung perfusion scan is recommended to discriminate selective endothelial damage from loss of vascular bed. PMID- 7863032 TI - MR imaging of minamata disease: qualitative and quantitative analysis. AB - Minamata disease (MD), a result of methylmercury poisoning, is a neurological illness caused by ingestion of contaminated seafood. We evaluated MR findings of patients with MD qualitatively and quantitatively. Magnetic resonance imaging at 1.5 Tesla was performed in seven patients with MD and in eight control subjects. All of our patients showed typical neurological findings like sensory disturbance, constriction of the visual fields, and ataxia. In the quantitative image analysis, inferior and middle parts of the cerebellar vermis and cerebellar hemispheres were significantly atrophic in comparison with the normal controls. There were no significant differences in measurements of the basis pontis, middle cerebellar peduncles, corpus callosum, or cerebral hemispheres between MD and the normal controls. The calcarine sulci and central sulci were significantly dilated, reflecting atrophy of the visual cortex and postcentral cortex, respectively. The lesions located in the calcarine area, cerebellum, and postcentral gyri were related to three characteristic manifestations of this disease, constriction of the visual fields, ataxia, and sensory disturbance, respectively. MR imaging has proved to be useful in evaluating the CNS abnormalities of methylmercury poisoning. PMID- 7863033 TI - [Validity of clinical signs and provocative tests in carpal tunnel syndrome]. AB - The relevance of EMG study was assessed to ascertain the diagnosis of carpal tunnel syndrome in cases of positivity of clinical signs and provocative tests. A prospective study was conducted in 60 patients presenting 85 symptomatic hands. Correlation between 11 signs and tests (isolated or associated) was performed with EMG used as "standard". None of the signs or tests reached an acceptable level of sensitivity, specificity or predictive value. This exam was positive in only 62 per cent of cases. EMG seems to mandatory before deciding on surgical release of the carpal tunnel syndrome. PMID- 7863034 TI - [Acetabular anteversion in congenital luxation of the hip]. AB - MATERIAL AND METHOD: Acetabular anteversion angle (AAA) and orientation angle of the iliac bone (AOOI) determined by use of a CT scan were studied in CDH. 55 children with CDH were selected on hip arthrography for this study. Subluxated hips were excluded (i.e. opposite hip of a unilateral CDH is normal). 10 boys and 45 girls with a mean of age of 2 years 1 month (extremes from 1 to 4 years 3 months) were studied. CT scan was performed before any orthopaedic treatment in 3 cases of bilateral luxation and 14 cases of unilateral. In the other cases, time between the end of orthopaedic treatment and CT scan varied between 4 and 18 months. A group of 23 normal children, 10 boys and 13 girls, (mean age of 2 years 10 months) served as reference group. On the selected CT slide we measured AAA, AOOI, IAA and IAP (anterior acetabular index and posterior acetabular index as proposed by Guggenheim). RESULTS: We noted that the orientation of the iliac bone was variable in the two groups. This orientation angle could have higher or lower values. AAA: in bilateral luxation, this angle was higher (16 degrees +/- 5 degrees) than in reference group (13 degrees +/- 4 degrees), p < 0.005. In unilateral luxation there was no statistical difference (14 degrees +/- 4 degrees) with reference group, between normal and pathological side and when CT scan was performed before or after orthopaedic reduction. AOOI: there was no significant difference between bilateral, unilateral or reference group. Correlation analysis showed that AAA and AOOI moved in the same direction. IAA: in bilateral luxation this index was higher (p < 0.001); in unilateral luxation only right luxation showed an higher index (p = 0.002). IAP: no significant difference between the different groups. DISCUSSION: This study shows that there is any typical CT scan aspects of morphologic abnormality in CDH. The lesions of the anterior or posterior acetabular wedge are variable. The orientation of the iliac bone is also variable; we concluded that acetabular anteversion must be analysed depending on the morphologic aspects of the anterior and posterior extremities of the acetabulum and iliac bone orientation. PMID- 7863035 TI - [Total knee prosthesis. Clinical and numerical study of micromovements of the tibial implant]. AB - INTRODUCTION: The importance of the micromovements in the mechanism of aseptic loosening is clinically difficult to evaluate. To complete the analysis of a series of total knee arthroplasties (TKA), we used a tridimensional numerical model to study the micromovements of the tibial implant. MATERIAL AND METHODS: Fifty one patients (with 57 cemented Porous Coated Anatomic TKAs) were reviewed (mean follow-up 4.5 year). Radiolucency at the tibial bone-cement interface was sought on the AP radiographs and divided in 7 areas. The distribution of the radiolucency was then correlated with the axis of the lower limb as measured on the orthoradiograms. The tridimensional numerical model is based on the finite element method. It allowed the measurement of the cemented prosthetic tibial implant's displacements and the micromovements generated at bone-ciment interface. A total load (2000 Newton) was applied at first vertically and asymetrically on the tibial plateau, thereby simulating an axial deviation of the lower limbs. The vector's posterior inclination then permitted the addition of a tangential component to the axial load. This type of effort is generated by complex biomechanical phenomena such as knee flexion. RESULTS: 81 per cent of the 57 knees had a radiolucent line of at least 1 mm, at one or more of the tibial cement-epiphysis jonctional areas. The distribution of these lucent lines showed that they came out more frequently at the periphery of the implant. The lucent lines appeared most often under the unloaded margin of the tibial plateau, when axial deviation of lower limbs was present. Numerical simulations showed that asymetrical loading on the tibial plateau induced a subsidence of the loaded margin (0-100 microns) and lifting off at the opposite border (0-70 microns). The postero-anterior tangential component induced an anterior displacement of the tibial implant (160-220 microns), and horizontal micromovements with non homogenous distribution at the bone-ciment interface (28-54 microns). DISCUSSION: Comparison of clinical and numerical results showed a relation between the development of radiolucent lines and the unloading of the tibial implant's margin. The deleterious effect of lower limbs' axial deviation is thereby proven. The irregular distribution of lucent lines under the tibial plateau was similar of the micromovements' repartition at the bone-cement interface when tangential forces were present. A causative relation between the two phenomenaes could not however be established. Numerical simulation is a truly useful method of study; it permits to calculate micromovements which are relative, non homogenous and of very low amplitude. However, comparative clinical studies remain as essential to ensure the credibility of results. PMID- 7863036 TI - [Mechanical performance of non slotted small diameter nails of Gross and Kempf]. AB - The goal of this study was to evaluate the mechanical properties of closed section small diameter Grosse-Kempf tibia nails. This type of implant has been advocated for an unreamed nailing of open tibia fractures in order to avoid further damage of bone blood supply and an increased risk for compartment syndrome. Static and dynamic tests were performed on 9 and 10 mm nonslotted Grosse-Kempf (G-K) and Russel-Taylor (R-T) nails. Results were compared with the properties of a 11 mm slotted G-K nail, considered as the reference nail. Axial loading tests were realized on nailed cadaver tibiae after resection of a midshaft bone segment. 3 points bending tests have shown a mean diminution of the elastic limit of 50 per cent, and a 25 per cent decrease of the bending rigidity for the closed section nails, as compared with the slotted reference nail. The rigidity in torsion was on the other hand 10 times higher with the nonslotted nails, which is a direct consequence of the elimination of the slot. Axial loading tests performed on isolated implants have given comparable results for all types of nails, including the reference nail. Nailed tibiae axially loaded demonstrated a stable bone-implant interface for loads up to 200 daN, with a mean displacement of 2 mm for a 50 daN load, whatever the type of the nail. Bending tests achieved on locking screws have indicated that G-K screws are twice as rigid as R-T screws.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863037 TI - [Treatment of femoral and tibial septic pseudarthrosis by internal lengthening. Apropos of 24 cases]. AB - Twenty two patients aged 18 to 47 years were treated for 24 infected bone defects and nonunions (6 femora and 16 tibiae) by radical resection of the necrotic bone and distraction osteogenesis techniques to regenerate the excised bone. Nonunion, infection, limb shortening, deformity, and osteoporosis were all addressed simultaneously. All patients underwent either bifocal or trifocal internal lengthening by bone transport technique of sliding a bone fragment, producing distraction osteogenesis behind it until the defect was bridged. The mean bone defect was 8.2 cm, with a range up to 16 cm. Eradication of the infection was achieved in all cases prior to the removal of the fixator. Problems with union requiring bone graft augmentation were encountered in three patients. One patient, who sustained a refracture, underwent an amputation. The mean time to union was 4.4 months, if the time was taken from the day the intercalary segment came in contact with the targed segment. Deformity and length inequality were corrected successfully in the majority of the patients. The bone result was excellent in 15 cases, good in 7, fair in one, and poor in one. The functional result was excellent in 11 cases, good in 8, fair in 3, and poor in 2. Distraction osteogenesis treatment seems to be superior to any other method used for treatment of infected bone defects and nonunions, especially in terms of eradication of osteomyelitis and quality of bone union. However, the ability to achieve excellent bone result in even the worst infected bone defects and nonunions does not guarantee a favourable functional result, unless the patient has an acceptable neurovascular status. PMID- 7863038 TI - [Interlocking nail according to Seidel in recent diaphyseal fractures of the humerus. Review of 41 cases of 48 fractures]. AB - The Seidel's humeral interlocking nail is used in our department since december 1986. We report about the 48 first cases, 41 of them have been reviewed with a mean time follow up of 14 months. The indications were humeral mid-shaft fractures with associated lesions (20 cases), failures of non operative treatment (10 cases) and compound fractures (7 cases). Primary radialis nerve lesions has to be explored before nailing. In 41 cases we used a static procedure; post operative immobilisation average time: were 13 days. Consolidation occurred in all cases within an average time of 10.5 weeks. Post-operative complications consisted in 1 case of infection healed after removal of the nail, and 1 case of secondary displacement after dynamic nailing with secondary radio-circumflex paralysis. The results were appreciated concording to the criteria of Stewart and Hundlay. We noted 64 per cent excellent and good results for fractures of the upper third, 80 per cent for fractures of the middle third and 85 per cent for the distal third of the diaphysis. All transverse fractures had a very good result but also the transverse and spiral fractures with third fragment which represent very unstable fractures especially at the upper third. The closed interlocking nailing of the humeral fractures according to Seidel represents a reliable and stable fixation method. Consolidation occurs in all cases whatever the type or the level of fracture. PMID- 7863039 TI - [Tibiotarsal arthrodesis: value of external fixator associated with in situ cancellous bone graft. Initial results apropos of 18 cases]. AB - Tibio-talar arthrodesis poses some problems and the most frequent are non-union and varus malalignment of the ankle joint. The aim of this report was to present a new technique of ankle joint arthrodesis. The principles of this procedure are as follows: firstly, the external fixation (A.L.J.) is framed, secondly, perpendicular cuts are made in the tibial plafond and talus through an anterior longitudinal approach; and thirdly, the gap is filled with cancellous bone graft which is taken preferably on the iliac crest. If the back-foot is not correctly lined up preoperatively, the external device is framed in two steps: the first step consists in putting the pins. Then perpendicular cuts are made, and the back foot is correctly lined up using calcaneal pins. The second step consists in connecting tibial pins and foot pins using union-rods. The last step of the procedure is to fill the gap with cancellous bone graft. The external fixation device is removed after 45 days and a shortleg walking cast is put for 45 days. Between 1981 and 1992, 18 arthrodesis were performed on various diagnosis: 9 post traumatic tibio-talar osteoarthritis, 4 residual neurologic diseases, 2 rheumatoid arthritis and 3 recent post-traumatic lesions. There were 17 patients (one bilateral case), 4 females and 13 males; the middle age at the time of operation was 44.5 years (20 to 60) and there were 10 right ankles and 8 left. The tibio-talar arthrodesis was performed alone in 14 cases, but it was associated with a talo-calcaneus arthrodesis in 4 cases. The after care was without complications except 3 pins infection which cured with antibiotics. All the cases had a good bony union within 3 to 6 months and the orientation of the backfoot was always satisfactory without varus malalignment. All the patients could put one's shoes without having recourse to orthopaedic shoes. In conclusion, this operative procedure seems to minimize the problems and pittfalls of the ankle arthrodesis. PMID- 7863040 TI - [Internal plantar flap. Apropos of 30 cases]. AB - Thirty medial plantar flaps were used in twenty seven patients with large defects in soft tissues of the lower extremity. We performed that flap described in 1981 by Harrison for ankle defects (9 cases) and heel defects (21 cases). The etiology of the defect was a traumatic avulsion in 14 cases, a sole pressure in 10 cases and neurologic ulcer in 6 cases. The surgical procedure was performed in 5 operative sequences: 1--excision of the receptor site 2--disection of the posterior tibial artery and plantaris medialis artery 3--raising of the flap including plantar skin and aponeurosis, respecting the flexor hallucis brevis muscle 4--rotation of the flap and suture on the receiptor site 5--skin graft on the donor site Antibiotics were used according to the per-operative swabs. Full weight bearing was authorized on the 45th day. We observed no failure for heel localization. But in dorsal part of the ankle, we deplore 4 failures (on 9 cases). The rotation for ankle defects was rather important and the risk was squeezing the artery. We used 3 times the medial plantar flap as a cross foot. We observed 1 failure; the possibility of long pedicled flap (parallel legs), the innocuity for the donor site, the quality of the transferred skin are arguments for using that flap in a cross leg of rather small dimension. We successfully performed two more cross legs using this technique since that study. We think that the medial plantar flap is the best technique for heel reconstruction. The quality of the skin transferred is very able to make a secondary thickening reproducing exactly the consistence of the heel. The fiability of that flap is very high for the heel localisations (no failures on 21 cases). PMID- 7863041 TI - Arteriovenous fistula complicating operative treatment of an ununited tibial fracture. AB - We report the case of a traumatic arteriovenous fistula of the peroneal vessels following a bone graft operation for an un-united tibial fracture. The fistula was recognised as a result of a bruit at the site of the fracture. The fistula was repaired and the fracture subsequently united. PMID- 7863042 TI - [A case of dislocation of a double patella]. AB - The congenital dislocation of the patella is relatively rare and the duplicated patella associated is exceptional. The congenital character of the dislocation is unquestionable, but the etiology remains unknown. Before patellar ossification, the diagnosis is difficult and may be delayed for several years until progressive genu valgum, external tibial rotation and flexion deformity results. Radiographs are not useful in evaluating the dislocation until patellar ossification begins at approximately 4 years of age. CT scans and MR imaging reveal the diagnosis before patellar ossification and defines the magnitude of associated dysplasia and the presence of degenerative changes. Early treatment is recommended before the development of secondary bony deformity. We are reporting an unusual case of a woman with multiple epiphyseal dysplasia and bilateral congenital malformation of the patella (duplicated frontal type), associated with genu valgum and congenital dislocation of the patella. She was diagnosed at 31 years old. After surgical treatment (genu valgum correction by varus osteotomy, proximal and distal realignment of the extensor mechanism and osteosynthesis with screws of duplicated patella) and three years follow-up period, we have obtained a good result (painless knees, no recurrence of dislocation and active flexion of 100 degrees on the right knee and 120 degrees on the left knee). PMID- 7863043 TI - [Double use of sural fascio-cutaneous flap with distal pedicle to cover loss of substance of ankle or heel]. AB - The authors report on a case of a distally based fascio-cutaneous flap from the sural region which has been used twice to cover two different cutaneous sites of an ankle. A 50 years old patient underwent a polytrauma including an open fracture of the ankle. The wound at the anterior aspect of the ankle did not heal and the cover by a distally based fascio-cutaneous sural flap was decided and realized successfully. Three weeks later, owing to the development of an ulcer of the heel, it was decided to cover this skin ulceration with the same distally based flap. This second procedure needed a complementary dissection at the bottom of the flap. Twenty days later, the remaining flap was put back and the uncovered donor site was skin-grafted. The two sites covered by the flap healed, without any further complications. They only benefited in the following months of plastic revision to improve their shapes. In the discussion the authors remind the anatomic basis of this distally based flap, described by Donsky and Fogdestam in 1983. They also discuss the other possibilities to cover these two lesions on the same ankle, using others flaps particularly the lateral supra malleolar flap described by Masquelet, the medial plantar island skin flap described by Harrison and Morgan, the lateral calcaneal skin flap described by Grabb and Argenta and the neuro-vascular island skin flap proposed by Masquelet et al. This clinical case emphasizes on the great interest of the distally based sural flap in the cover of the skin defect of the ankle. The flap is easy to raise and offers a great available skin surface, which can be used, as demonstrated by this original case, in two different sites of the ankle. PMID- 7863044 TI - [Respiratory stimulants and COPD]. PMID- 7863045 TI - [Almitrine bismesylate treatment in chronic respiratory insufficiency]. AB - This study was designed to evaluate the gasometric and functional respiratory responses in chronic bronchitic patients with chronic respiratory insufficiency (CRI) under ambulatory oxygen therapy (AOT) with almitrine bismesylate (AB). It was a double-blind, placebo-controlled, randomized, prospective study which lasted three months and with a dosage regime of 50-100 mg/day of AB. Fiftyfour patients completed the study (28 in AB and 24 in the placebo (P) groups, respectively). All patients were males, with a mean age or 65 +/- 6.1 years. In the study of pulmonary function only airway resistance (Raw) was changed, with a significant decrease at the third month in the AB group compared with the P group (0.83 +/- 0.31 vs. 1.07 +/- 0.46 kpa/L.S), with a p value of 0.05 (mean +/- SD) and PaO2 which improved from 8.15 +/- 0.88 to 8.81 +/- 2.3 kpa (61.17 +/- 6.6 to 66.10 +/- 10 mmHg), with a p value of 0.05. AB therapy was well tolerated. PMID- 7863046 TI - [Endobronchial metastasis. Clinical aspects, diagnosis and course in a series of 27 cases]. AB - Our 10-year experience is reviewed of 27 cases of endobronchial metastasis diagnosed by bronchoscopy. Primary tumors were breast (15 cases), kidney, bladder, rectum and melanoma (two cases each), and stomach, gingiva, amygdala and penis (one case each). Their presentation was prior to primary neoplasm in two patients, simultaneously in three, and posterior in the remaining patients (mean 64 +/- 52 months). Half of patients also had extrathoracic metastasis. In cases of breast cancer systemic chemotherapy was administered and the median survival rate was 24 months, significantly longer than in the remaining group (3 months); in the later, symptomatic therapy predominated due to the common involvement of lung parenchyma and functional deterioration of patients. PMID- 7863047 TI - [Variations of angiotensin converting enzyme in chronic obstructive pulmonary disease and chronic respiratory insufficiency]. AB - Maintained hypoxia has been reported to induce inactivation of the Angiotensin Converting Enzyme (ACE). Variations have also been observed in patients with chronic obstructive pulmonary disease (COPD) who have chronic hypoxemia and loss of the vascular endothelium. OBJECTIVES: 1) to determine serum ACE activity in patients with COPD treated with and without continuous ambulatory oxygen therapy (CAOT); 2) to verify whether there is a correlation between ACE and any hematological, spirometric or gasometric parameter. METHODS: fifty-eight patients fulfilling clinical and spirometric parameters of COPD were studied. Patients were assigned to two groups of therapy: A) Group A, without Continuous Ambulatory Oxygen Therapy (CAOT): 31 males and 1 female (mean age: 64.8 +/- 6.52). B) Group B (with CAOT): 23 males and 3 females (mean age years: 63.76 +/- 8 years). The following procedures were performed: spirometry, gasometry, blood chemistry, and serum ACE measurements by means of a radioenzymatic assay. The Student "t" test with the Bonferroni correction and Pearson regression analysis were used for the statistical analysis. RESULTS: significant differences were observed for ACE values between Group A and Group B: 42.81 +/- 11.30 vs. 33.40 +/- 9.43 mumol/min/l, with a p value of 0.001, and also between Group B and reference values: 33.40 +/- 9.43 vs. 39.70 +/- 9.65 mumol/min/l, with a p value of 0.002. No differences were observed between Group A and reference values. No correlations wer found between ACE and any of the variables studied. CONCLUSIONS: ACE was not decreased in all patients with COPD. ACE was decreased only in patients with COPD and respiratory insufficiency requiring CAOT and with advanced disease. This results can be correlated with changes in vascular endothelium, pulmonary parenchyma and metabolism. It could be a marker of poor prognosis or advanced disease. PMID- 7863048 TI - [Comparative study of 2 diagnostic tests of aspecific bronchial hyperreactivity]. AB - Bronchial challenge test are useful in diagnosis of bronchial hyperresponsiveness (BH). To assess the sensitivity of histamine test (HT) and exercise test (ET), 45 asthmatic patients (31 men, 14 women, ages 9-34) with normal resting pulmonary function test were studied. HT and ET were performed in two different days. HT was positive in 40 (6 severe, 23 moderate and 11 mild) and ET was positive in 13 (88.8% vr 28.8%, p < 0.001). All patients with positive ET had positive HT. There is a relationship between the degree of BH severity and the response to ET (chi 2 = 5.995; p < 0.05). The HT has a high profitability the diagnosis of BH. The ET has a low sensitivity. PMID- 7863049 TI - [Endoscopic treatment of bronchopleural fistula using fibrin biological adhesive]. AB - Three cases are reported of bronchopleural fistula successfully resolved by using biological adhesives through the intrabronchial way. In the three cases the rigid bronchoscope was used to prepare the field and the passage of the adhesive material. The results obtained allow the consideration of this procedure as useful for small fistulas and as a initial therapeutical approach for other fistulas due to the small morbidity rate associated with this procedure compared with others. PMID- 7863050 TI - [Bronchiolo-alveolar carcinoma: review of 14 cases]. AB - Fourteen cases are revised of bronchiolalveolar carcinoma (BAC) diagnosed in our institution from 1980 to 1992. The time interval from clinical manifestations to diagnosis was 5.13 +/- 6.01 months. The incidence of smokers in the population was 42.8%. Clinical findings were non-specific, except in three cases, consisting in bronchorrhea with more than 100 ml. The most frequent site of the tumor was bilateral and diffuse (71%), mainly in nonsmokers. Endoscopic findings suggested a likely malignancy in 21% of cases. Transbronchial biopsy was the most sensitive diagnostic method. Histological confirmation was obtained in 85% of cases. To note the possible association with Epstein-Barr virus (EBV), as demonstrated by the findings of EBV genome in the cases when this study was performed. PMID- 7863051 TI - [Screening of prostate cancer]. PMID- 7863052 TI - [Intratracheal tumor in a 67-year-old man]. PMID- 7863053 TI - [Differential diagnosis of a pulmonary mass]. PMID- 7863054 TI - [Pneumonia with a torpid course. Any underlying abnormality?]. PMID- 7863055 TI - [Management of patients with chronic obstructive pulmonary disease]. PMID- 7863056 TI - [Glaucoma secondary to uveal disorders]. PMID- 7863057 TI - [Usefulness of endomysial antibodies in the diagnosis of celiac disease in adults]. PMID- 7863058 TI - [Ventilatory function and respiratory pattern in smokers and nonsmokers]. PMID- 7863059 TI - [Bronchoalveolar lavage in bronchiolitis obliterans with pneumonia in idiopathic organization]. PMID- 7863060 TI - [Pontine infarction and cervical herpes zoster]. PMID- 7863061 TI - [Descriptive epidemiology of bovine theileriosis caused by Theileria annulata in Mauritania, Subsaharian West Africa]. AB - Tropical bovine theileriosis due to Theileria annulata has been discovered recently in Mauritania. An epidemiological study performed in the dry season allowed to better determine the serological prevalence of T. annulata infection and its associated factors. The sex does not seem to have any influence, the role of the breed could not be clearly established, whereas, the age, the geographical origin and the management of the herd have a significant influence on the serological prevalence. These results were compared with those of the tick fauna. Hyalomma dromedarii appears to be the natural vector over the whole Mauritanian territory. However, the more diversified the tick fauna is (lower valley of Senegal River), the highest is the serological prevalence. The incidence survey in the rainy season, performed exclusively in the Senegal River valley, raises the question of the role of Rhipicephalus evertsi evertsi, strictly limited to this area, which could be responsible for an amplifying phenomenon of transmission. The clinical survey in the dry season as well as in the rainy season did not reveal any clinical cases. Therefore, a stable endemic situation appears to exist between the local zebu and T. annulata infection in Mauritania. PMID- 7863062 TI - Suspicion of a case of lymphocytic leukaemia in a camel (Camelus dromedarius) in Sultanate of Oman. AB - The peripheral blood picture of a suspected case of lymphocytic leukaemia in a dromedary camel is described. The authors discuss their findings. This condition seems rare in comparison with the results of a large number of blood samples examined during the last ten years. PMID- 7863063 TI - [Caprine arthritis-encephalitis in Algeria]. AB - During an outbreak of caprine arthritis-encephalitis on an experimental farm, the virus responsible for this disease was isolated from imported animals. A serological survey was then carried out with the purpose of determining the prevalence of the disease among other imported herds of goats, local herds and mixed herds. Positive serological results were found at relatively high levels in both imported and mixed herds. All the local herds, however, yielded negative serological results, suggesting that caprine arthritis-encephalitis did not exist in Algeria before the importation of reproductive animals with a high genetic potential. PMID- 7863064 TI - Seasonal prevalence of ticks and their association with dermatophilosis in cattle on the Accra plains of Ghana. AB - The seasonal abundance of adult ticks on cattle and their association with dermatophilosis were investigated in five herds on the coastal plains of Ghana over a 26-month period. Four genera, Amblyomma, Boophilus, Rhipicephalus and Hyalomma were identified, A. variegatum being the predominant species occurring throughout the year with two peaks of infestation, one in April-May and the other in November. A significant positive correlation was revealed between A. variegatum and dermatophilosis in four of the five herds. Significant positive correlations were found between H. m. rufipes and dermatophilosis in two of the herds and between Rh. senegalensis and dermatophilosis in one herd. Negative correlations of statistical significance were observed between Boophilus species and dermatophilosis in three of the herds. Nevertheless, it was considered that A. variegatum was the most important tick factor involved in the pathogenesis of the disease. PMID- 7863065 TI - [Factors and markers of virulence of Escherichia coli strains isolated from diarrhea in calves aged 4-45 days in Algeria]. AB - The study involved 492 strains of Escherichia coli isolated from the feces of 44 diarrhoeal calves and 4 healthy calves in 7 wilayates in Algeria (Tipaza, Ain Defla, Bejaia, Borj Bou Arreridj, Bouira, Medea and Algiers). The authors looked for the surface proteins K99, CS31A, Vir, F17 (FY), 20K and certain factors or markers of virulence such as the production of colicins, particularly colicin V, the aerobactin siderophore, alpha hemolysin and enterohemolysin. They also studied the frequency of certain 0 serogroups and evaluated the resistance of the E. coli strains to 10 antibiotics. The results showed that the majority of diarrhoeal calves were colonized by Escherichia coli expressing one or more factors of virulence and that the stocks which produce the antigen CS31A are usually resistant to 4 or 6 antibiotics. PMID- 7863066 TI - A clinical note on Haemophilus aegyptius infection in sheep in Nigeria. AB - An outbreak of Haemophilus aegyptius infection in a livestock farm located in Maya, Oyo State, Nigeria is reported. Diagnosis was based on clinical signs of central nervous system disturbance, histopathological findings of meningoencephalomyelitis, acute multifocal necrotising purulent hepatitis and the isolation of Haemophilus aegyptius from the spinal cord. Other diseases that can cause nervous disturbance are discussed. PMID- 7863067 TI - Pathogenic aerobic bacteria and fungi isolated from stray dogs in Trinidad. AB - The occurrence of pathogenic aerobic bacteria and fungi in 100 stray dogs was investigated. The most commonly isolated pathogens were Staphylococcus aureus, S. intermedius and Malassezia pachydermatis. No zoonotic pathogen was isolated. It is suggested that stray dogs may not maintain or transmit the pathogens. PMID- 7863068 TI - Onchocerca gutturosa infection of the ligamentum nuchae in two cows in the Sudan. AB - Severe lesions of the ligamentum nuchae are described for the first time in two cows in the Sudan. Post mortem and histopathological examination of the nodules reveals inflammatory process the causal agent of which is Onchocerca gutturosa. PMID- 7863069 TI - First isolation of Trichophyton verrucosum as the aetiology of ringworm in the Sudanese camels (Camelus dromedarius). AB - A survey was conducted to study camel ringworm in Eastern Sudan. Ringworm was diagnosed in 217 out of 498 young camel calves under two years old examined during a whole year (43.5%). The peak incidence of the disease was found to be in Autumn and Winter. The disease was observed more frequently among young growing calves (1-2 years) than older animals but the prevalence among male and female animals was found to be similar. Lesions were observed mainly on the head, neck and shoulder with frequent extension to the flanks and limbs. Trichophyton verrucosum was isolated in pure culture for the first time from camel ringworm in the Sudan. Histopathological findings of the natural disease are described. Epidemiology in Eastern Sudan is discussed. PMID- 7863070 TI - [Prevalence of Trypanosoma infections in different species of wild animals in the Comoe national park on the Ivory Coast: preliminary results of the comparison of 3 diagnostic methods]. AB - Compared with the numerous studies of trypanosomosis in domestic animals, few such studies have been carried out on wild animals in West Africa. Preliminary results on the comparison of three detection methods (thin smears, detection of trypanosome antigens by ELISA-Test and Kit for in vitro isolation of trypanosomes, KIVI) in wild animals of Comoe Game Reserve in Cote d'Ivoire confirm the actual presence of trypanosomes; however, no accurate identification of those parasites has been possible, but work is in progress to clarify the taxonomical status of stocks isolated by KIVI. PMID- 7863071 TI - Serum biochemical changes in West African Dwarf sheep experimentally infected with Trypanosoma brucei. AB - Serum and plasma biochemical values were determined in female West African Dwarf sheep experimentally infected with Trypanosoma brucei. The results show an increase in the values of serum iron, chloride, bicarbonate, inorganic phosphate, creatinine, urea, total protein, globulin and plasma fibrinogen. The serum albumin, albumin/globulin ratio, potassium, copper and magnesium values are depressed. These findings suggest detective re-utilization of iron in erythropoiesis and probable paratathyroid gland, hepatic and/or renal malfunction. PMID- 7863072 TI - [Quasi-absence of trichostrongylid reinfection in Gambian livestock during the dry season]. AB - Five Ndama bulls aged between 1.5 and 2 years and 20 Djallonke rams aged between 6 to 18 months were dewormed as follows: the bulls were dewormed in November (beginning of the dry season), the sheep were divided into four groups dewormed in November, January, March and May respectively. The animals were kept on naturally infected pastures prior to and throughout the experiment. Gastrointestinal nematode egg excretion was measured weekly after starting the treatment. Egg excretion stayed practically nil for all animals except for the series of sheep treated in May which started excreting eggs on month after the first rain. The bulls were slaughtered in June and the sheep were slaughtered nine weeks after they had been initially dewormed. A complete parasitological post mortem examination confirmed the absence of any pathologically consequent reinfection by gastro-intestinal nematodes of Gambian cattle during the dry season. This confirms the strategic importance of the application of a dewormer also efficient against immature trichostrongylids at the beginning of the dry season and renders complementary deworming between November and May superfluous. PMID- 7863073 TI - Serum disappearance and urinary excretion of sulfamethoxypyridazine in goats. AB - Pharmacokinetics and urinary excretion of sulfamethoxypyridazine were determined in goats following single intravenous administration (100 mg/kg body weight). The disposition kinetics of sulfamethoxypyridazine could be best described by a 2 compartment open model. The distribution and elimination half life of the drug were 0.10 +/- 0.03 and 6.28 +/- 0.44 h, respectively. The values of apparent volume of distribution at steady state and total body clearance were found to be 0.39 +/- 0.02 l/kg and 0.73 +/- 0.06 ml/kg/min, respectively. The degree of acetylation was low as it ranged between 4.49 +/- 1.96 to 25.07 +/- 6.31% of the total drug in serum with an overall mean of 11.99 +/- 1.66%. Cumulative urinary excretion of sulfamethoxypyridazine was very low as only 2.97 +/- 0.50% of the total administered dose was excreted in urine during 24 h. The dosage regimen in goats would be 37.00 and 27.15 mg/kg body weight as the priming and maintenance doses respectively, to be repeated at 12 h intervals by intravenous route to achieve the bacteriostatic level of > or = 25 micrograms/ml. PMID- 7863074 TI - [Efficacy and residual effect of amitraz (Taktic) on adult Hyalomma dromedarii in camels: preliminary trial]. AB - Amitraz (12.5% emulsifiable concentrate) was tested against Hyalomma dromedarii of the one-humped camel in a dairy camel herd in Nouakchott (Mauritania), at a concentration of 0.025% of the active component. The efficacy on adult ticks and the rapid rate of tick detachment are clearly shown: 95% reduction within eight hours; however, the nymphs seem to be more resistant: only 50% reduction after eight hours. The residual activity of amitraz against Hyalomma dromedarii in camels is very short, less than 24 hours; furthermore, the amitraz treatment has no effect on survival, oviposition and the rate of egg hatching of females which attach in the first days following treatment. A discussion of likely causes of this phenomenon is presented. PMID- 7863075 TI - [Technetium-99m isonitrile versus thallium 201 in coronary disease]. PMID- 7863076 TI - [Evaluation of myocardial viability by isotopic methods]. PMID- 7863077 TI - [Advantages of SPECT versus planar technique in nuclear cardiology]. PMID- 7863078 TI - [Evaluation of myocardial damage with radioactive isotopes]. PMID- 7863079 TI - [Use of pharmacological-stress echocardiography]. PMID- 7863080 TI - [Quantitative analysis in the evaluation of coronary stenosis]. PMID- 7863081 TI - [Role of percutaneous angioscopy in the study of coronary lesions]. PMID- 7863082 TI - [Uses of magnetic resonance in cardiology: initial experience in 100 cases]. PMID- 7863083 TI - [Clinical usefulness of exercise echocardiography]. PMID- 7863084 TI - [Multiplane transesophageal echocardiography: technique, methodology and uses. Comparison of monoplane and biplane techniques]. PMID- 7863085 TI - [Doppler echocardiography in the evaluation of valvular regurgitations]. PMID- 7863086 TI - [Intraoperative echocardiography]. PMID- 7863087 TI - [Intracoronary ultrasonics: a new window for diagnostic and therapeutic assessment of transluminal procedures]. PMID- 7863088 TI - [Imaging techniques in the diagnosis of aortic pathology]. PMID- 7863089 TI - [Transesophageal echocardiography in childhood]. PMID- 7863090 TI - Recent results in cancer research. Introduction. PMID- 7863091 TI - Hereditary and familial breast tumors. PMID- 7863092 TI - Hereditary and familial ovarian cancer. PMID- 7863093 TI - Genetic factors in lung cancer. PMID- 7863094 TI - Genetic factors in precancerous lesions and cancer of the esophagus. PMID- 7863095 TI - Genetic predisposition and environmental factors in gastric carcinoma. PMID- 7863096 TI - Hereditary and familial colorectal cancer. PMID- 7863097 TI - Hereditary gastrointestinal polyposis syndromes. PMID- 7863098 TI - Biomarkers of increased susceptibility to cancer. PMID- 7863099 TI - Familial aspects in carcinoma of the pancreas. PMID- 7863100 TI - Li-Fraumeni syndrome. PMID- 7863101 TI - Genetic factors in leukemia and lymphoma. PMID- 7863102 TI - Familial factors in cancer of the genitourinary tract. PMID- 7863103 TI - Cancer-prone hereditary diseases associated with abnormalities of DNA repair. PMID- 7863104 TI - Familial tumors of other organs. PMID- 7863105 TI - Oncogenes and tumor suppressor genes. PMID- 7863106 TI - Genetic factors in solid tumors of childhood. PMID- 7863107 TI - Retinoblastoma. PMID- 7863108 TI - Multiple endocrine neoplasia. PMID- 7863109 TI - Hereditary tumors of the nervous system. PMID- 7863110 TI - Genetic aspects of diseases: categories of genetic disorders. PMID- 7863111 TI - Hereditary melanoma and dysplastic nevus syndrome. PMID- 7863112 TI - Nutritional aspects of cardiovascular disease. Report of the Cardiovascular Review Group Committee on Medical Aspects of Food Policy. PMID- 7863113 TI - [Gout in black Africa]. PMID- 7863114 TI - [Vascular manifestations of dermatomyositis and polymyositis. Clinical, capillaroscopic and histological aspects]. AB - Polymyositis is characterized by a T-cell-mediated and MHC-I-restricted cytotoxic process, whereas dermatomyositis is a primitively vascular disease with microangiopathy mediated by the complement C5b-9 membranolytic attack complex. We have tried to estimate the frequency of vascular abnormalities in polymyositis as defined by Bohan and Peter. We have retrospectively studied 17 patients with dermatomyositis and 15 patients with polymyositis. Vascular abnormalities have been defined by clinical, capillaroscopic and histologic (muscle biopsy and minor salivary glands biopsy) features. After clinical features, 5/17 dermatomyositis had a Raynaud's phenomenon, against 6/15 polymyositis. Digital necrosis has been observed for 2/17 dermatomyositis and 2/15 polymyositis. In capillaroscopy, 14/17 dermatomyositis had a microangiopathy with or no enlarged capillary loops, against 7/15 polymyositis. None of these polymyositis had enlarged capillary loops. The muscle biopsy showed a predominantly perivascular or perimysial inflammatory infiltrate (vascular process) for 10/16 dermatomyositis against 4/13 polymyositis; a perifascicular atrophy for 3/16 dermatomyositis against 2/13 polymyositis. The histological study of minor salivary glands, showed vascular lesions for 2/11 dermatomyositis and for 1/8 polymyositis. Finally, Bohan and Peter's classification is now inadequate to distinguish between dermatomyositis and polymyositis. Indeed, some dermatomyositis sine dermatitis, may exist and be recognized by their vascular features. To distinguish between dermatomyositis and polymyositis is important, to evaluate the risk of cancer which is more frequent in dermatomyositis. PMID- 7863115 TI - [Xanthomonas maltophilia nosocomial infections. A new threat. Apropos of 30 cases]. AB - In an attempt to further characterize infections due to Xanthomonas maltophilia, we reviewed 20 colonisations and 30 infections observed in our institution from january 1990 to december 1992, Xanthomonas maltophilia is emerging as an important nosocomial pathogen in immunocompromised patients, especially those receiving broad spectrum antimicrobial antibiotherapy. Distinction between colonisation and infection is often difficult. Xanthomonas maltophilia presents a therapeutic challenge because of its tendency to exhibit multiple resistance. PMID- 7863116 TI - [Specific respiratory manifestations of Horton disease]. AB - Several respiratory manifestations have been described in patients with temporal arteritis. These complications may develop at the onset of the disease or later. Cough is the most frequent of them. Other complications include pleural effusions, interstitial pneumonitis, pulmonary vasculitis. Hyperreactive airways, hoarseness, diaphragm paralysis have been noted. Generally, corticosteroids cause a prompt improvement. Physicians should be aware of respiratory symptoms in patients with temporal arteritis in order to avoid delays in diagnosis and therapy. PMID- 7863117 TI - [Introduction to the process of oncogenesis: cancers are somatic genetic diseases]. AB - Cancers are the most frequent and at the same time the most complicated of somatic genetic diseases. Technical progress in the last fifteen years has enabled to analyse the acquired genetic abnormalities found in the vast majority of cancers. This molecular dissection of cancer has led to an understanding of this disease that can basically be viewed as a rupture of the balance between two class of genes, the oncogenes and the antioncogenes. This article defines the properties of these cancer genes and gives through a few examples an insight into the various mechanisms of cancerogenesis. PMID- 7863118 TI - [Hyperthyroidism and hypersecretion of chorionic gonadotropin in gastric adenocarcinoma]. AB - We report a case of hyperthyroidism complicating and revealing a metastatized adenocarcinoma of the stomach with high circulating levels of human chorionic gonadotropin and its beta component. To our knowledge, this is the first reported case of a non-trophoblastic tumor with hyperthyroidism and secreting quantities of these hormones. High circulating levels of beta component in such patients have been considered to be a sign of malignancy. The mechanisms of thyroid stimulation could be related to the biological activity of certain forms of the human chorionic gonadotropin. PMID- 7863119 TI - [Destombes-Rosai-Dorfman syndrome: 2 uncommon clinical forms]. AB - Two cases of Destombes Rosai Dorfman's syndrome are presented. Diagnosis was performed by superficial lymph node biopsy. The first case concerned a nine and half years old girl with cervical adenopathy who developed a compressive mediastinal adenopathy responsible for a right lower lobe atelectasis. Because of local lung suppuration a lobectomy had to be performed. The second case concerned a fourteen years old boy with recurrent fever, diffuse superficial lymph nodes and erythematous skin rash. The two patients showed clinical and biological inflammatory symptoms without any immunodeficiency. No aetiological agent could be identified. Antibiotics and corticoids had no effect but the two patients recovered (after 18 months follow up in case 2). These two particular cases confirm the clinical course heterogeneicity of the syndrome which requires histological diagnosis. PMID- 7863120 TI - [Coxiella burnetti pleuropericarditis]. AB - We report here a case of acute fever with pleuropericarditis and high levels of Coxiella burnetti antibodies (phase II), excluding other possible etiologies. Complete recovery occurred with the use of non-steroidal anti-inflammatory agents combined with tetracycline. PMID- 7863121 TI - [Cerebral amyloid angiopathy apropos of a case. Review of the literature]. AB - The authors present the case of an 83 year-old man with cerebral amyloid angiopathy who had three successive lobar intracerebral hematomas within 4 weeks. There were neither a predisposing familial factor nor cardiovascular risk factors nor any other cause favouring cerebral bleeding. The autopsy revealed amyloid deposits in small cortical and meningeal arteries. No other lesions of the Alzheimer's disease was found. PMID- 7863122 TI - [Unresectable giant hepatic hemangioma and Kasabach-Merritt syndrome]. AB - The Kasabach-Merritt syndrome was first described in children with cutaneous hemangiomas, but it can exceptionally be associated with visceral hemangiomas, especially in adults. Clotting and fibrinolysis within the hemangioma are thought to cause the coagulopathy observed in the so-called Kasabach-Merritt syndrome. This localised form of intra-vascular coagulation can progress to a secondary increased systemic fibrinolysis with fatal outcome for 20 to 30% of the patients. A transient control of hematologic abnormalities can frequently be obtained with blood product support (platelets, fibrinogen, fresh plasma, cryoprecipitates) and heparinotherapy. But in the adult, the only radical alternative is surgical excision if technically feasible. We reported here the case of a 43 year-old woman with a giant unresectable hepatic hemangioma complicated with a Kasabach Merritt syndrome. PMID- 7863123 TI - [Disorder of the supra-aortic trunks]. PMID- 7863124 TI - [Medical ethics and partnership with industry]. PMID- 7863125 TI - [Leser-Trelat sign and hypercorticism associated with metastatic adenocarcinoma of unknown origin]. PMID- 7863126 TI - [Value of biliary tubage in the diagnosis of acute pancreatitis without recognized etiology]. PMID- 7863127 TI - [Reversible acute left ventricular insufficiency induced by interferon]. PMID- 7863128 TI - [Tussive form of Horton disease]. PMID- 7863129 TI - [Pathogeny and strategies of prevention of type I diabetes]. PMID- 7863130 TI - [From the natural history of non-insulin-dependent diabetes and its etiopathogenesis]. PMID- 7863131 TI - [Diabetes and atherosclerosis. Physiopathology of diabetic macroangiopathy]. PMID- 7863132 TI - [The future of the treatment of insulin-dependent diabetes mellitus]. PMID- 7863133 TI - [Sarcoidosis: definition and immunological approach]. PMID- 7863134 TI - [Endothoracic sarcoidosis]. PMID- 7863135 TI - [Osteoarticular manifestations of sarcoidosis]. PMID- 7863136 TI - [Rare sites of sarcoidosis: clinical aspects and reflections on the diagnostic approach]. PMID- 7863137 TI - [Treatment of sarcoidosis]. PMID- 7863138 TI - Features of good consultation in general practice: is time important? AB - OBJECTIVE: To relate specifically defined 'good consultations' (GC) to length of consultation, continuity, patients' age and sex, and different doctors. DESIGN: A questionnaire about consultation length, communication and problem character, given to doctors and patients immediately after consultations. MAIN OUTCOME MEASURES: The number of GCs for different doctors in relation to time, continuity, and patients' age and sex were calculated. SETTING: 581 consultations were registered with six male general practitioners working at three different health centres in Umea, a university town in northern Sweden. RESULTS: A significant difference in the number of GCs was only found between the doctors (p < 0.01). Length of consultation, patients' age and sex, and continuity and no impact on the GC frequency. CONCLUSION: The doctor as a person and his working style is most important in achieving good consultations in general practice. Length of consultation is less influential. PMID- 7863139 TI - A wet smear criterion for bacterial vaginosis. AB - OBJECTIVE: To evaluate a simpler criterion for bacterial vaginosis than the recommended criterion of Amsel. DESIGN: Cross-sectional study comparing diagnostic data with a recommended standard. SETTING: Danish general practice. PARTICIPANTS: 595 non-pregnant women aged 15-49 years who were gynaecologically examined, were divided into two groups in accordance with a complaint of vaginal discharge. MAIN OUTCOME MEASURE: The associations of pH > 4.5, homogeneity, amine odour, clue cells, and wet smear assessment of predominance of lactobacilli, Gardnerella vaginalis, motile rods with the criterion of Amsel. RESULTS: The four components of Amsel showed a considerable variation of association. Predominance of GV was more highly associated than several of the components. The association of a wet smear criterion composed of the presence of clue cells in combination with predominance of Gardnerella vaginalis and absence of lactobacilli was superior to other combinations. In the group without a complaint of vaginal discharge, preceding screening with use of a pH-measurement seemed advantageous. CONCLUSION: The wet smear criterion seems suitable for use in general practice. But before a definitive establishment, calculation of the reproducibility of interpretation of this criterion, preferably with a more explicit setting of the components, has to be carried out. PMID- 7863140 TI - Vaginal application of lactobacilli in the prophylaxis of recurrent lower urinary tract infection in women. AB - OBJECTIVE: To examine whether vaginal application of Lactobacillus casei v. rhamnosus reduces the reinfection rate in cystitis-prone women. DESIGN: A controlled, randomized, double-blind clinical trial. SETTING: Division for General Practice, University of Bergen, Norway. INTERVENTION: Vaginal application of lactobacilli twice weekly. SUBJECTS: 47 women, aged 18-50 years, reporting three or more episodes of distal urinary symptoms during the previous 12 months, of which at least one episode had been medically verified as a lower UTI. MAIN OUTCOME MEASURE: The incidence rate of lower UTI during 6 months' follow-up. RESULTS: No difference in infection rate between the two groups; the incidence rate ratio between the treatment group and the placebo group was 1.41 (95% confidence interval 0.88-1.98). Lactobacilli were not found more frequently periurethrally in the treatment group than in the control group. CONCLUSION: It is still uncertain whether vaginal application of lactobacilli reduces the infection rate in cystitis-prone women. PMID- 7863141 TI - Overweight, underweight and mortality among the aged. AB - OBJECTIVE: To clarify the influence of overweight and underweight on the total mortality as well as on different causes of death in an unselected population of old people. DESIGN: The cohort of the aged population was examined in 1971. The survival time of the cohort was followed for ten years. SETTINGS: Rural commune of Hankasalmi in Central Finland. PARTICIPANTS: 721 (80% of total aged population) subjects aged 65 years or over (310 men and 411 women). OUTCOME MEASURES: 10 years survival rate and causes of death by body mass index quartiles and sex. RESULTS: The women in the lowest BMI quartile had the highest mortality in ten-year follow-up (a 26% decrease in survival time). The differences between the total mortality of the other quartiles were small. In the lowest BMI quartile there was overmortality from respiratory diseases and tumours, and undermortality from cardiovascular diseases. In the highest BMI quartile the main groups of causes of death did not differ essentially from those in the whole cohort. CONCLUSION: Underweight was as strong a predictor of mortality, and even stronger, than overweight. PMID- 7863142 TI - Characteristics of participating and nonparticipating men in a randomized, controlled diet and exercise intervention trial. AB - OBJECTIVE: To study characteristics of importance for participation in a diet and physical exercise prevention programme. SETTING: Primary Health Care, Sollentuna, and the Karolinska Hospital, Stockholm, Sweden. SUBJECTS: A sample of 187 men, aged 35-60, with increased risk factors for CHD, were invited to a 6-month prevention programme. Participants (n = 158) were randomized into a diet group, a physical exercise group, a diet and physical exercise group, and a control group. Twenty-seven men, who declined participation, formed the group of nonparticipants. DESIGN: Participants and nonparticipants were compared with respect to health beliefs, health knowledge, CHD risk factors, demographic and personality factors. MAIN OUTCOME MEASURES: Characteristics of men participating and not participating in the intervention trial. RESULTS: Nonparticipants, compared with participants, believed less in the benefits of dietary change and perceived the health threat of stroke and myocardial infarction as less serious. Nonparticipants had a better knowledge of a number of risk factors for cardiovascular disease. CONCLUSION: Belief in treatment efficacy and perceived health threat, rather than health knowledge, predicted initial participation in a non-pharmacological intervention trial. PMID- 7863143 TI - Oral glucose tolerance test in general practice--when is it worthwhile? AB - OBJECTIVE: To examine the probability of impaired glucose tolerance and diabetes, diagnosed with oral glucose tolerance test, at different levels of fasting blood glucose. DESIGN: When indicated, fasting capillary whole blood glucose was measured. Patients with blood glucose ranging from 4.4 to 6.6 mmol/l had an oral glucose tolerance test. SETTING: General practice. SUBJECTS: 355 patients had an oral glucose tolerance test. RESULTS: 33% had impaired glucose tolerance and 12% had diabetes. One or more diabetics were found at every level of fasting blood glucose. The probability of finding a diabetic was ten times larger in the fasting blood glucose stratum 6.1 to 6.6 mmol/l than in the fasting blood glucose stratum 4.4 to 4.9 mmol/l. Likelihood ratio increased 30 times from the lowest to the highest stratum. No cutoff point in the interval 4.4 to 6.6 mmol/l had both a high sensitivity and a high specificity for the diagnosis of diabetes. CONCLUSION: If it is of great importance to find every patient with impaired glucose tolerance and diabetes, one has to do an oral glucose tolerance test in every fraction of the fasting blood glucose range 4.4 to 6.6 mmol/l (according to WHO's diagnostic criteria). Using 5.2 mmol/l as a cutoff point for an oral glucose tolerance test, the sensitivity is still high (0.95), but one would miss a few with diabetes. PMID- 7863144 TI - Oral glucose tolerance and its relationship to overweight and other cardiovascular risk factors in men aged 33-42. A study in the community of Habo, Sweden. AB - OBJECTIVE: To study the prevalence of family history of diabetes, overweight, and glucose intolerance in a defined general population, and the associations between these variables and others involved in the so-called metabolic syndrome (blood pressure, obesity, serum lipids). DESIGN: An oral glucose tolerance test (OGTT) was done on all participants in a population study who reported a family history of diabetes or had a body mass index (BMI) > or = 27. SETTING AND PARTICIPANTS: A population study of men aged 33-42 was carried out at Habo in southwestern Sweden (participation rate 86.1%). An OGTT was done on 170 men who fulfilled the criteria stated above. RESULTS: Overweight was a risk factor for impaired glucose tolerance and was more strongly associated with this state than was a family history of diabetes. Glucose intolerance was also associated with increased blood glucose concentration during the OGTT and with other metabolic disturbances such as increased serum lipids, increased blood pressure, and physical inactivity. CONCLUSIONS: The combination of overweight and impaired glucose tolerance is already common at a rather young age in men and is often combined with impairment of arterial blood pressure and serum lipids. The results indicate that it is urgent to start preventive measures early in life. PMID- 7863145 TI - Do pregnant women who report a reduction in cigarette consumption consume less tobacco? AB - OBJECTIVE: To investigate the relationship between changes in self-reported cigarette consumption and changes in serum thiocyanate among pregnant and non pregnant women who participated in a smoking cessation trial. DESIGN: Intervention study. SETTING: General practitioners in western Norway. SUBJECTS: 146 pregnant and 102 non-pregnant women who were daily smokers at inclusion. Self reported cigarette consumption and serum thiocyanate were recorded at inclusion and after 12 months. RESULTS: Women who smoked in the first trimester of pregnancy reported 21% less cigarette consumption than non-pregnant women. This was in accordance with the serum thiocyanate values. Twelve months later the mean values of serum thiocyanate had increased irrespective of whether the postpartum women reported that they had reduced, increased, or not changed their cigarette consumption. However, among those who reported that they had stopped smoking, analyses of serum thiocyanate confirmed their statements, with very few exceptions. Among nonpregnant women, the serum thiocyanate changed in accordance with the reported changes in cigarette consumption in all groups. CONCLUSION: Women smoking daily in the first trimester of pregnancy had a lower exposure to tobacco than daily smoking non-pregnant women. Twelve months later (six months after delivery) analyses of serum thiocyanate indicated that postpartum women underestimated their tobacco consumption. PMID- 7863146 TI - Mixed use of psychiatric drugs and alcohol by Finnish university students participating in a health screening. AB - OBJECTIVE: To obtain descriptive data on the mixed use of psychiatric drugs and alcohol. The difference and associations of health and mental risk factors between mixed users and others were also studied. DESIGN: A self-administered questionnaire as part of a general health screening. SETTING: First-year university students enrolled in the Finnish Student Health Service in Helsinki. Foreign students and those aged 30 years or over were excluded. SUBJECTS: 3,836 students were invited. The participation rate was 73.2% for the female and 53.2% for the male students. RESULTS: The mixed use of psychiatric drugs and alcohol with the aim of getting high, at least once, was reported by 3.6% of the female and 3.1% of the male students. However, only 1.0% had tried this mixed use more than once. Mixed users were more often smokers, heavy drinkers, or users of cannabis or heavy drugs. Male students tended to be mixed users because of anxiety, low self-esteem, and fears. Depression, stress, and sensation seeking were associated with mixed use in female students. CONCLUSIONS: Mixed use of psychiatric drugs and alcohol by young Finnish university students is still rare. There is a strong accumulation of other addictive behaviours among mixed users. Extra-personal reasons for mixed use were more prevalent among female students, and intra-personal reasons among male students. PMID- 7863147 TI - Cholesterol management in Dutch general practice. A comparison with national guidelines. Dutch College of General Practitioners. AB - OBJECTIVE: To examine cholesterol diagnosis and treatment by Dutch general practitioners (GPs) in the period before publication of national guidelines, in order to develop implementation strategies based on discrepancies found between daily practice and the guidelines. DESIGN: Data of the 'Dutch National Survey of General Practice', in which GPs were involved in extensive consultation registration, were used. Patients were included for analysis if serum cholesterol, or the ICPC-code lipid metabolism disorder, or cholesterol-lowering treatment was registered. SETTING: General practice. PARTICIPANTS: 161 GPs, 177 practice-nurses. OUTCOME MEASURES: Reasons for consultation, diagnoses, therapy, inter-doctor variation. RESULTS: The main discrepancies between daily practice and the guidelines concerned indications for cholesterol measurement, repeated measurements to diagnose hypercholesterolaemia, and attention for diet advice. A remarkable inter-doctor variation in diagnosis, and less so in treatment, was also found. CONCLUSION: The inter-doctor variation justifies the publication of the standard guidelines. Implementation strategies should aim at indications for cholesterol testing, repeating measurements for diagnosis, and advice on diet. PMID- 7863148 TI - Risk factors for cardiovascular disease and their relation to age and educational level among middle-aged women. Study of middle-aged women in a rural area. AB - OBJECTIVE: To investigate the occurrence of risk factors for CVD and their relation to age and educational level among middle-aged women in a rural area. DESIGN: A descriptive study of all middle-aged women (40 to 59 years) in the area. SETTING: A parish in middle Sweden (Ostervala). PARTICIPANTS: All women born 1930-1949 in the parish of Ostervala (324 on 1 October 1988). MAIN OUTCOME MEASURE: Total serum cholesterol, Serum triglycerides, LDL/HDL ratio, F-blood glucose, Blood-pressure, Body Mass Index and Waist/Hip circumference Ratio as well as quality of life factors as reported in a questionnaire. RESULTS: For all variables examined there was a significant difference between lower and higher educated women except for fasting blood glucose, serum triglycerides and quality of life scores, in favour to the more educated group. The number of risk factors for CVD were increased with age but decreased with education. Quality-of-life scores were lower in individuals experiencing pronounced stress than in less stressed individuals. Life-quality scores were higher among able-bodied persons than among those with a reduced capacity to work or unemployed persons. The number of risk factors were surprisingly high in many women. An intervention programme will be initiated. Further studies will show whether it is possible to decrease the number of risk factors and as a consequence the standardized mortality rate. PMID- 7863149 TI - A cost-effectiveness study of leg ulcer treatment in primary care. Comparison of saline-gauze and hydrocolloid treatment in a prospective, randomized study. AB - OBJECTIVE: The majority of leg ulcer patients in Sweden are managed by primary health care personnel. To compare, in a primary care setting, the healing results and the expenses of two commonly used wound dressings for leg ulcers. DESIGN: Thirty patients with leg ulcers of venous or mixed venous/arterial aetiology were randomized to treatment with saline-soaked gauze or with the hydrocolloidal dressing [HCD: DuoDERM (ConvaTec, A Bristol-Myers Squibb Company, Princeton)]. All patients were bandaged with the same compression of low-stretch-type [Comprilan (Beiersdorf AG, Hamburg)]. SETTING: Vardcentralen Marieberg, Primary Health Care Centre, Motala, Sweden. OUTCOME MEASURES: Healing/reduction of ulcer area, pain, costs for material, nursing time, kilometres driven were registered during a six-week period. RESULTS: Two patients dropped out of the study, one in the gauze-group due to erysipelas, and one in the HCD-group for social reasons. A total of 1234 dressing changes were analysed. Costs for material were similar in the two groups. When the total care including nursing- and travelling time and kilometres driven were analysed, the mean cost for treatment with gauze dressings was 4126 Swedish Kronor (SEK), and with HCD, 1565 SEK. Seven patients in the HCD group and two in the gauze-group healed during the study. The reduction of the ulcer area was 19% in the gauze-group and 51% in the HCD-group (p < 0.16). CONCLUSION: The total care, analysed in an authentic clinical setting, must be considered when different wound-care methods are discussed. In this study the use of HCD showed lower costs than use of gauze-dressings. As regards healing there was a tendency to improved healing with HCD, but no significant difference. Patients in the HCD-group reported significantly less pain at dressing changes (p < 0.003) than patients in the gauze-group. PMID- 7863150 TI - [Paraneoplastic cerebellar degeneration]. AB - Paraneoplastic cerebellar degeneration (PCD) is a rare complication of systemic cancer. PCD may present as a "pure", severe pan-cerebellar syndrome of subacute progression or be only one clinical feature in the setting of extensive CNS disease. The most characteristic form of "pure" PCD is associated with the presence of an anti-Purkinje cell antibody (AB), called anti-Yo, in patients with breast or ovarian cancer. The primary tumor is very often unknown when the cerebellar signs occur, and extensive investigations, including laparotomy or prolonged follow-up may be required to demonstrate its presence. More rarely, others AB than anti-Yo are discovered during PCD. Almost 50% of patients with "pure" PCD do not have circulating anti-neuronal AB. In the cases, the primary cancer is more often known and the clinical course of the cerebellar syndrome may be slower. Cerebellar degeneration may also occur during paraneoplastic encephalomyelitis. In this setting, the cerebellar signs which may be isolated at the onset, become associated with other signs of neuraxis involvement (limbic encephalitis, brainstem encephalitis, myelitis and particularly, subacute sensory neuronopathy) during the course of the disease. When a paraneoplastic encephalomyelitis is associated with a small cell lung cancer, an antineuronal AB called anti-Hu is frequently found. Finally PCD may be associated with the opsoclonus-myoclonus syndrome with the Lambert-Eaton syndrome. PMID- 7863151 TI - [Effect of naftidrofuryl (LS129) on axonal growth]. AB - The response of growing axons and microtubules to naftidrofuryl (LS 129) was investigated in vitro and in situ in the embryonic nervous system of mice. For this purpose, we used rotatory cultures of post-implanted embryos in a rat or human serum containing the compound combined with immunofluorescence using a tubulin-specific polyclonal antibody on high molecular weight polyethylene-glycol embedded semithin sections. We also analysed the protective effect of naftidrofuryl to treatment with vinka alkaloids using the same method. After culture in rat serum enriched with naftidrofuryl at concentration of 20 microM and above, we observed an increase of both the number of axonal profiles in semithin sections and of the number of microtubules per surface unit in electron micrographs. After culture in human serum obtained from an healthy volunteer after a unique intake of naftidrofuryl at 900 mg/j and above, we observed the same effect of an increasing of the number of axonal profiles in the tectal plate of mice embryos in semithin sections. These results suggest a promoting effect of naftidrofuryl on axonal growth and on microtubules' assembly. They suggest a therapeutic effect of this drug at daily doses of 900 mg/j. After culture in a rat serum enriched with naftidrofuryl at concentration of 20 microM, we observed a protective effect of this drug toward the disruption of axonal microtubules by vinka alkaloids. This effect seems rather specific since we did not observe the same protection toward the mitotic microtubules. These results suggest that naftidrofuryl could be used to prevent the neurological side effects of vinka alkaloids. PMID- 7863152 TI - [Cerebral lymphoma in AIDS: clinical study and clinicopathological correlations]. AB - We report the natural history of 17 brain lymphomas (11 primary, 6 disseminated) from a post-mortem series of 130 patients with AIDS. Primary lymphomas appeared lately in the course of AIDS. They were often associated with a severe T-cell immunodepression and with more frequent opportunistic disorders than disseminated lymphomas. Associated Kaposi's sarcomas were surprisingly frequent. All patients presented with neurological manifestations. Heterogeneous features were seen at CT examination. The CSF was abnormal in 12/13 cases, with an increase of protein contents and secretion of immunoglobulins; it contained activated lymphocytes in 5/6 cases of disseminated lymphomas, and malignant cells in only one case. Cellular density never exceeded 8/mm3 for primary lymphomas, and the lymphocytes were considered normal. The pre-mortem diagnosis of cerebral lymphomas was made in five patients, with a time lapse of 1 to 7 months between the first neurological symptoms and death, and of 5 to 30 days between the diagnosis and death. Cerebral biopsy was diagnostic in 4 cases of primary cerebral lymphomas. In only 1/6 patients with disseminated lymphomas, the diagnosis had been made when the patient was still alive, based on CSF and bone marrow lymphomatous infiltrations. The diagnosis of cerebral lymphoma (7 primary, 5 disseminated) was post-mortem in 12 cases. It was made only at microscopic examination in 2/12 cases of primary lymphomas. The histopathological study frequently showed a multicentric involvement, and always an immunoblastic cell type with plasmablastic differentiation and frequent medium size cells. Marked gliosis and significant necrosis were often observed. Neuropathological lesions associated with HIV-1 infection (toxoplasmosis, CMV and HIV-1 encephalitis) were seen in 8 cases with primary lymphomas. PMID- 7863153 TI - [A study of 82 cerebral infarctions in the area of posterior cerebral arteries]. AB - Of 598 consecutive non-selected cases of cerebral infarction included in a stroke registry, 82 cases (54 men and 28 women, mean age 66 +/- 14 years) of spontaneous and isolated posterior cerebral artery (PCA) territory infarction (right PCA in 36, left PCA in 35 and both in 11) were identified on the basis of CT combined with MRI in 51 cases. Infarction was superficial in 25 (group A), combined deep superficial in 23 (group B) and deep in 34 (group C). Of 48 superficial lesions, 29 were massive while 19 were restricted to the territory of one branch. Of 57 deep lesions, 21 were located in the inferolateral thalamic territory, 10 in the paramedian thalamic territory, 12 in other midbrain or thalamic territories, and 14 in a combination of various midbrain and/or thalamic territories. Of 41 patients with unilateral superficial involvement, 39 had homonymous visual field defect. Unawareness of the visual defect and visual release hallucinations were observed with the same frequency in right and left lesions. Of 7 patients with bilateral superficial involvement, only 5 had bilateral visual field defect including incomplete cortical blindness in 3. The frequency of confusional state (n = 24) did not differ significantly in left versus right sided lesions while it was significantly higher in superficial or combined versus deep lesions (p = 0.05). Of 18 clinically evaluable patients with left PCA territory infarct, 14 had speech disorders including pure alexia in only one case. Of 15 patients with right territory infarction, 10 had spatial judgement disorders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863154 TI - [Hereditary myasthenic syndromes with late onset. Value of electrophysiological tests]. AB - A myasthenic syndrome was diagnosed in 3 female patients aged 37, 47 and 56 years. The symptoms were first noticed in childhood, and at 16 and 25 years. Respectively weakness and atrophy of finger extensor muscles were present in all patients. In 2 of them scapular and cervical muscles were involved. Weakness was markedly increased by cold in every patient. Similar symptoms were noted in first degree relatives in all cases. Single nerve stimulus elicited a repetitive compound muscle action potential in hand muscles. Repetitive nerve stimulation induced a myasthenic decrement in finger extensor muscles. SFEMG studies demonstrated increased jitter with frequent blockings. Genetic, clinical and electrodiagnostic data were consistent with the hypothesis of the so-called "Slow Channel" myasthenic syndrome. As 2 of these patients were considered to have "unknown myopathy" the use of careful nerve stimulation tests is advocated in such cases. PMID- 7863155 TI - [Neuropathies of septic syndrome with multiple organ failure in burnt patients: 2 cases with review of the literature]. AB - We report two cases of axonal sensori-motor polyneuropathies complicating sepsis and multiple organ failure (MOF) among severely burned patients (total burned surface area of 35 to 40 per cent) in which no other cause of neuropathy was retrospectively identified. No steroids or neuromuscular blocking agents had been given. The date of onset was not established but the diagnosis was late, between the 30th and 45th day, at the recovery of consciousness. Regression was incomplete, with severe sequellae especially in one patient who was unable to walk 10 months after the injury. Burned patients can present with many kinds of peripheral neuropathies. Postburn polyneuropathies with nerve conduction slowing were described by Henderson. Mononeuropathies can result from nerve compression complicating unfavorable postures in comatose patients or from nerve entrapment in ischemic limbs. Polyneuropathy in postburn sepsis with MOF does not appear to have been previously reported. Postburn sepsis usually occurs in young patients, without other cause of MOF; and therefore represents a relatively "pure" sepsis syndrome. PMID- 7863156 TI - [Benign multiple sclerosis with childhood onset]. AB - We report a case of multiple sclerosis which began at the age of 12 years. Clinical symptoms at onset were acute, regressive cerebellovestibular ataxia and optic neuritis. Twenty-four years later vertigo, motor and sensory deficit of the right lower limb and grand mal seizures developed. CSF and MRI were suggestive of multiple sclerosis. The patient is now free of neurological symptoms with an 8 years' follow-up. PMID- 7863157 TI - [Marchiafava-Bignami disease: interhemispheric disconnection, Balint syndrome, spontaneously favourable outcome]. AB - We report a new case of Marchiafava-Bignami disease with favourable outcome. This case is particular on several scores. The interhemispheric disconnection syndrome was associated with Balint's syndrome, and this had apparently never been reported in this context previously. Despite the intensity and diffusion of white matter lesions in both hemispheres, and in the absence of vitamin treatment, the clinical and neuroradiological (CT, MRI) improvement occurred early and rapidly. This course, similar to that of toxic drug withdrawal, suggested that this was not a process of vitamin deficiency. Data from the literature indicate that a wide extension of corpus callosum lesions to the semi-ovale centre has a poor vital and functional prognosis. Our case shows that this is not always correct and that the appearance of intralesional necrosis and cavitation is not the rule. We consider that the most reliable factor of poor prognosis seems to be an initial coma. PMID- 7863158 TI - [Agenesis of the corpus callosum, heterotopia of the gray cortex and interhemispheric cyst. Late radiologic diagnosis in an asymptomatic adult]. AB - Agenesis of the corpus callosum may occur as an isolated finding; most often, it is present in association with other cerebral malformations such as cortical heterotopias. Computerized tomography and magnetic resonance imaging are methods of choice to detect these cerebral prenatal abnormalities, especially asymptomatic forms. We report the case of an asymptomatic young adult with complete callosal agenesis, cortical heterotopia and interhemispheric cyst, on CT and MR imaging. PMID- 7863159 TI - [Intradural hematoma of the foramen magnum associated with factor XIII deficiency]. AB - A 50-year-old woman, with a history of IgG monoclonal gammapathy, presented with meningitis and intradural hematoma of the foramen magnum associated with factor XIII deficiency. The patient died postoperatively of diffuse haemorrhage. Inhibitors to factor XIII are extremely rare and are congenital or acquired. Patients with factor XIII inhibitor can experience severe bleeding, and many died of cerebral haemorrhage. The role of this defect is discussed. We recommend an extensive investigation of haemostasis for patients with both episode of haemorrhagic disorder and monoclonal gammapathy. PMID- 7863160 TI - [Encephalopathy and Hashimoto thyroiditis]. AB - A generalized epileptic seizure revealed a subactute encephalopathy which was attributed to Hashimoto's thyroiditis. Primary biliary cirrhosis was also discovered. The encephalopathy rapidly followed a favourable course under corticosteroid therapy, which confirms that it was an immune disease. PMID- 7863161 TI - [Multifocal motor neuropathy]. AB - We report the case of a patient with multifocal motor neuropathy. Electrophysiological studies showed typical multifocal conduction blocks, but the search for anti-GM1 antibodies was negative. This case provide the heterogeneity of this clinical entity. PMID- 7863162 TI - [Confrontation at Salpetriere hospital. March 1992. Coma and hemiplegia with fast fatal outcome in a 47 year-old man]. PMID- 7863163 TI - [Surgery for temporal lobe epilepsy]. AB - Interest in surgery for intractable temporal lobe epilepsy has increased during the last ten years, mainly due to a better identification of the epileptogenic focus by modern imaging techniques (MRI) or functional tools (TEP and SPECT scanning). Depth electrodes recording is not mandatory and can be restricted to patients who do not meet congruent non invasive criteria. Simultaneously, modification of surgical techniques has been proposed: in addition to classical temporal lobectomy, other methods are used in order to minimize the resection of temporal lateral neocortex, and increase that of mesial temporal structures; the latter can be selectively performed through amygdalo-hippocampectomy. Outcome of surgery is generally excellent or good. More than three-fourths of patients are seizure free or show major reduction in seizure frequency. Outcome at the end of the second year is a good indication of long-term prognosis. PMID- 7863164 TI - [Changes of some proteins expression of the spinal cord and muscles in infantile spinal muscular atrophy]. AB - The various types of childhood spinal muscular atrophy (SMA) represent a spectrum of clinical disorders resulting from the degeneration of motor neurons (MN). The genetic defect has been recently localized to chromosome 5q in the region 11.2 13.3. Under normal conditions, half of the motor neurons die during embryonic development, while the remaining 50% survive to innervate muscle fibers and form neuromuscular junctions. Numerous studies using in vivo and in vitro models have shown that survival of MNs depends on the presence of trophic factors of neuronal and muscular origin. However, at the present time, no molecular mechanisms can be proposed to account for the nature and the sequence of the interactions leading to the formation and maintenance of a functional neuromuscular junction. To gain a better understanding of the SMA disorders, an alternative to genetic studies consists in analyzing the molecular mechanisms underlying this pathology. Variations in the expression of proteins, for instance, might reflect the pathological phenotype. We thought it possible to detect differences in the protein(s) which would correlate with the molecular deficit of childhood SMA. We, therefore, compared the patterns of human protein expression from normal controls and SMA spinal cord and muscle. Significant variations in the expression of some proteins, which have been quantified by a computerized Bio-Image electrophoresis system, have been found. In particular, two proteins, a and b (126 kDa and 112 kDa) which are very probably common to spinal cord and muscle show a marked increase of their expression in children with SMA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863165 TI - [Amnestic syndromes and confabulation in infarction of the posterior cerebral artery area]. AB - The Posterior Cerebral Artery (PCA) supplies the greatest part of the limbic system. Several authors have reported amnestic syndromes in PCA infarcts. Amongst 76 patients with a CT proven PCA infarct, 21 suffered anterograde amnesia. Confabulations were associated in 5 cases. We studied CT scans according to previously reported templates in the 21 amnestic patients: all patients with confabulations had a paramedian or a tuberothalamic infarct associated with a cortical infarct within the superficial territory of the PCA. None of the 16 remainders had a thalamic lesion. These results emphasize the role of the thalamus especially of the dorsomedial nucleus in the pathogenesis of confabulation. The underlying mechanism could imply fronto-cingular deafferentation. PMID- 7863166 TI - [Clinical and evolutive aspects of cerebellar infarction]. AB - This study included 125 cases of cerebellar infarction followed during an average period of 4.3 years. The diagnosis was made by CT or MRI. Infarctions localized to the territory of the superior cerebellar artery (SCA) and the territory of the posterior inferior cerebellar artery (PICA) occurred with the same frequency. Transient ischemic attacks preceded infarction in 26% of cases. Symptoms and signs were usual with sudden association of headache, dizziness, unsteadiness and vomiting. Vestibular signs were more important in infarctions of the PICA territory; cerebellar signs and dysarthria were more frequent in infarction of the SCA territory. A decreased level of consciousness developed in only 21% of cases. Surgical operation was required in 9 cases. Investigations have showed the large responsibility of cardiac embolisms and atherosclerosis. Short term outcome was more often favourable: 116 patients were alive at the end of the first month; 80% of survivors were independent one year later. At 5 years, 73% of patients were alive. After the acute period, mortality was mainly due to cerebro-vascular and cardiac events. PMID- 7863167 TI - [Single cerebral metastasis of bronchopulmonary cancers]. AB - The most frequent brain metastasis originates from a lung cancer. About half of them are unique. We report a series of 36 patients with lung cancer, operated for a single brain lesion. The mean age was 57.6 years, most (83.3%) were male. Most of the metastases originated from a primary adenocarcinoma (52.8%), in 10 patients (27.8%) from an epidermoid carcinoma, in 4 patients (11.1%) from a small cell carcinoma and in 3 patients from a mixed lesion. The metastatic lesion was detected before the primary lesion in 20 cases (55.5%). The mean post-operative survival was 9.6 months. 36% were alive one year after surgical treatment. We evaluated our clinical findings, histopathological studies and the type of surgical and medical post-operative management, at the cerebral and pulmonary level, in order to make a possible prognosis. In our series we found that only post-operative clinical status (Karnofsky score) and the post-operative neurological grading (Order classification) were significant factors (p < 0.001) to determine survival time. PMID- 7863168 TI - [Diagnostic and prognostic contribution of somatosensory evoked potentials by truncular and dermatomal stimulation in lumbosacral radiculopathy. Apropos of 120 cases surgically-treated]. AB - Lower-limb somatosensory evoked potentials (SEPs) of nerve-trunk (peroneal nerve, posterior tibial nerve) and dermatomal (L5 and S1) stimulation were recorded in 120 patients suffering from lumbosacral disk disease. Recordings were performed before surgery and on Days 4 and 50 after surgery. Electromyography was also performed before surgery. Dermatomal SEPs were shown to be sensitive (70%) and specific in both terms of their lateralizing value and their ability to identify the L5 or S1 level. Moreover, combining SEPs and EMG significantly increased the sensitivity of the electrophysiological testing when compared with each method alone. There was no relationship between SEPs performed before surgery and surgical outcome. Inversely, we demonstrated the prognostic value of SEPs performed on Day 4, SEP normalization at Day 4 was associated with a good outcome at Day 50 in 91.8% of examined cases, while the persistence of pathological SEPs at Day 4 was associated with poor outcome at Day 50 in 56% of the cases. PMID- 7863169 TI - [Post-traumatic interhemispheric disconnection syndrome]. AB - A left-handed man presented with a partial hemispheric disconnection syndrome of traumatic origin composed by a left hand unilateral agraphia, a left hand tactile anomia, a left visual field anomia, a left visual field alexia and a partial left ear extinction for verbal material. MRI of the brain showed lesion involving the trunk of the corpus callosum. PMID- 7863170 TI - [Primary meningeal gliomatosis]. AB - A 44 year old woman presented with chronic meningitis. Magnetic resonance imagery showed a diffuse contrast enhancement of the leptomeninges. Cerebrospinal fluid studies showed a high hyperproteinorachia and light pleiocytosis. A left temporal tumor appeared four months later. Histological studies revealed an anaplastic oligosatrocytoma leading to the diagnosis of primary leptomeningeal gliomatosis. PMID- 7863171 TI - [Unilateral paralysis of the glossopharyngeal, vagus and hypoglossal nerves]. AB - A 32-year-old woman complained of swallowing difficulty after a general seizure. Neurological examination revealed unilateral palsies of the 9th, 10th, and 12th cranial nerves. CT, MRI and internal carotid artery angiogram were normal. Selective catheterization of the external carotid artery and ascending pharyngeal system suggested a cranial nerve ischaemic arterial syndrome. The apparent sparing of the eleventh nerve may be explained by the double vascularization of this nerve. This may also be related to the double innervation of the trapezius and sterno-cleido-mastoid muscles by the 11th nerve and cervical spinal nerves. PMID- 7863172 TI - [Continuous partial epilepsy disclosing diabetes mellitus]. AB - Continuous partial epilepsy (CPE) is characterized by isolated, subintrant clonus focalized to a limited territory with critical focal electroencephalography in a concordant territory. CPE is observed in various cortical lesions but also in disorders of metabolism and notably decompensated diabetes mellitus. We report a case of CPE without focal lesion at MRI which revealed hyperglycaemia without ketosis. The 54-year old female patient was hospitalised for C.P.E.. Early CT and later MRI gave normal results. Biochemistry showed hyperglycaemia without kenoturia, acidosis or hyperosmolality. Insulin therapy rapidly brought glycaemia down to its normal level and the clonsism disappeared. Five months later, the patient had no other seizure and the EEG was normal. Epileptic seizures are frequent in hyperglycaemia without ketosis (25% of the cases) where they are mainly partial and motor (75 to 86% of the cases), rarely associated with a focal lesion (15% of the cases with CT scan). They are rare in patients with ketoacidosis. This apparent protective effect of ketoacidosis may be attributed to an increase of GABA bioavailability consecutive to acidosis. CPE is resistant to antiepileptic treatments. In CPE induced by hyperglycaemia without ketosis normalization of blood glucose level with insulin therapy is concomitant with a rapid cure of epilepsy. Thus glycaemia should be measured in all patients presenting with CPE, the aim being to diagnose hyperglycaemia without ketosis rapidly to avoid hyperosmolality and to prescribe an adequate treatment based exclusively on insulin and rehydration. PMID- 7863173 TI - [Unusual triggering circumstance of benign acute cerebral angiopathy; link with exertion cephalalgia?]. AB - Immediately following a scream of fear, a sixty-year old woman complained of severe bilateral headache which relapsed several times over the following month during exercise. There was no history of sympathomimetic drug intake. The work-up was normal save for minimal subarachnoid bleeding and the angiogram showed a disseminated "sausage-string" appearance over all cerebral arterial territories, without aneurysm. The unusual triggering event in this case and the subsequent recurrence of headache in relation to exercise lead us to discuss possible links between the clinical entity of "Isolated benign cerebral angiopathy" and exertional headache. PMID- 7863174 TI - [Lambert-Eaton syndrome without calcium channel autoantibodies]. AB - Two cases of Lambert-Eaton syndrome are reported, one associated with a small cell lung carcinoma, the other without any etiology at the time of the study. None of these cases showed significant titers of calcium channel autoantibodies. The heterogeneity of the Lambert-Eaton syndrome and the responsibility of the autoantibodies detected by immunoprecipitation of the voltage-gated calcium channel in the occurrence of the neuromuscular block are discussed. PMID- 7863175 TI - [Paretic syndrome of spinal stenosis]. AB - We report a case of painless progressive leg amyotrophy without intermittent claudication due to spinal lumbar stenosis. Our attention was drawn to the lumbar region because of the discrepancy between normal leg sensory potentials and altered somatosensory evoked potentials, prompting us to perform a myelography. The rapid though partial, clinical improvement following decompressive surgery suggested that some of the symptoms may have been due to a reversible nerve conduction block. PMID- 7863176 TI - [What is left of Morvan's fibrillary chorea?]. AB - In 1890, Morvan described a syndrome of myokimia associated with muscle pain, excessive sweating and sleep disorders. The course was severe and the patient died five weeks after the onset. Several cases were published after this first report in the French literature. The last for 10 years the disease seems to have disappeared. In fact, it seems that the progress in electromyography introduced clear definitions of spontaneous muscle discharges (myokimia, neuromyotonic discharges, fibrillations, fasciculations) allowing recognition of a disease characterized by a syndrome of spontaneous and continuous muscle fiber activity associated with cramping, slow relaxation (pseudomyotonia), excessive sweating and stiffness. Different terms have been used to describe this entity: neuromyotonia (Mertens and Zschocke, 1965) or continuous muscle fibre activity (Isaacs, 1961). Classification of these syndromes has to distinguish inherited from acquired forms, idiopathic cases from cases where neuromyotonia is associated with a peripheral neuropathy, a cancer or an immunological disease. Moreover, the frequent occurrence of this later association and recent reports of improvement after plasma exchanges suggest a possible autoimmune aetiology for this group. Finally, we suggest that the term of "Maladie de Morvan" must be used instead of choree fibrillaire but only concerning patients who exhibit central disorders including insomnia, hallucinations and altered behaviour. PMID- 7863177 TI - [Clinical and electroencephalographic manifestations during the Wada test using intracarotid injection of methohexital (Brietal)]. AB - In this retrospective study we report our 12 years' experience of the Wada test (intra-carotid injection of short half-life barbiturates) using Methohexital. The clinical manifestations induced by Methohexital were similar to those observed with Amobarbital. The inocuity of the test is attested by the finding that no incident or accident has been reported in 126 injections, the risk being the same as for arteriography. The two main advantages of Methohexital over Amobarbital are: 1) short hemispheric narcosis, which makes it possible to explore the two carotid arteries territories during the same session and limits the risk of drug diffusion to the two hemispheres; 2) the rare occurrence of vigilance troubles such as drowsiness or falling-asleep, which are frequently observed during Amytal Wada test. Intracarotid Methohexital injections are effective to determine the hemispheric lateralization of language and useful to evaluate the role of each hemisphere in memory, especially before the surgical treatment of drug-resistant focal epilepsies. PMID- 7863178 TI - [Apraxia and autotopoagnosia without aphasia or agraphia with compulsive language activity in right hemispheric lesion]. AB - A 75 year-old woman was admitted with a left hemiplegia resulting from an infarct in the right middle artery's territory. Her manual preference was ambiguous from early childhood. She presented with severe bilateral apraxia, autotopoagnosia, finger agnosia, and left spatial neglect. There was, however, no aphasia nor agraphia. When the patient attempted to perform gestures on order, she compulsively produced oral or written language. In this very unusual case, dominance for gesture and dominance for language were strictly independent, each ensured by one hemisphere. The patient's performances in gestual activities, especially dissociation between automatic and voluntary movements, and compulsive linguistic productions, are discussed in relation to this functional lateralization. We suggest that the propositional nature of the responses required in test conditions could activate either voluntary language in the left cerebral hemisphere, or voluntary gestures in the right. A competition between the two hemispheres could explain the patient's linguistic apraxic or behavior in response to orders. Autotopoagnosia, an uncommon symptom, could interfere with apraxia, but is not directly responsible. PMID- 7863179 TI - [Patent foramen ovale and paradoxical embolism: a controversial hypothesis]. AB - Twenty-four patients with a patent foramen ovale and unexplained ischemic cerebral events are reported. The conventional factors in favour of paradoxical embolism have been evaluated. Five patients (20.8%) mentioned a Valsalva manoeuver just before the onset of their neurological disorders. Only 2 deep venous thrombosis of the legs, one of which resulting from the ischemic event, could be detected. These results do not confirm the hypothesis of paradoxical embolism and are in disagreement with other recent studies. This discrepancy may be due to the choice of the patients. More stringent echocardiographic criteria should be considered in the future. PMID- 7863180 TI - [Infarction of the caudate nucleus or anterior striato-capsular infarction?]. AB - Eight patients with caudate nucleus infarcts are reported. The main clinical findings were often transient facio-brachial weakness (6 patients), depression (4 patients), subcortical aphasia with decreased spontaneous verbal activity (2 patients), and aboulia (2 patients). The ischemic lesions of caudate nucleus often extend into the adjacent anterior limb of the internal capsule and the anterior putamen owing to vascularization pattern. The specific clinical picture of this entity also includes lesions of nearby white matter tracts. Risk factors, etiology of infarcts, clinical findings and prognosis were similar to those reported in striato-capsular infarcts. We suggest replacing the term caudate infarct by anterior striato-capsular infarct. PMID- 7863181 TI - [Somatosensory evoked potentials in amyotrophic lateral sclerosis and primary lateral sclerosis]. AB - Somatosensory evoked potentials (SEPs) were studied in 21 cases of amyotrophic lateral sclerosis (ALS) and 7 cases of primary lateral sclerosis (PLS). Despite the lack of clinical sensory abnormalities, SEPs showed abnormalities in both diseases: lack or delay of some components. In ALS these abnormalities indicate widespread sensory disturbance. In PLS only, the Brodmann area 4 seems to be affected. PMID- 7863182 TI - [Autoimmune familial myasthenia in 2 sisters with a follow-up of more than 30 years]. AB - The clinical course of two sisters with myasthenia initially published in La Revue Neurologique in 1960 has been followed. Both had secondary severe respiratory impairment requiring a tracheotomy and mechanical ventilation. Thymectomy was performed in both and revealed residual thymic tissue. Complete remission was observed long after thymectomy even with the persistence of antiacetylcholine receptor antibodies which are still present in the older sister despite intercurrent autoimmune thyroiditis and in the younger sister despite the development of mediastinal lymphosarcoma leading to death 32 years after the onset of myasthenia. PMID- 7863183 TI - [Spasmodic laughter caused by unilateral involvement of the brain stem]. AB - We report a case of spasmodical laughter due to a strictly unilateral lesion located in the pons and the caudal part of the mesencephalon. Pathophysiology of this particular symptom is reviewed. PMID- 7863184 TI - [Cerebral hemorrhage disclosing metastatic choriocarcinoma]. AB - We report the case of a 28-year-old woman who presented with multiple episodes of cerebral bleeding secondary to a choriocarcinoma with brain, lung and abdominal metastases, which had been partially treated 1 year before. The diagnosis was confirmed by a-high serum beta HCG level. This case emphasizes the importance of suspecting an underlying choriocarcinoma and obtaining a serum beta HCG level in young women presenting with a cerebral haemorrhage. PMID- 7863185 TI - [Epileptic seizures and treatment with ifosfamide-mesna]. AB - Generalized and partial seizures with secondary generalization were observed during ifosfamide-mesna (IFO) treatment in a patient with lung epidermoid carcinoma. Seizures appeared in a stereotyped manner on the 3rd of the 4th and 6th day of treatment with IFO. Partially resolutive confusion was observed after the last cure. Brain CTS were normal. The responsibility of IFO is considered in the development of these neurological toxic manifestations. PMID- 7863186 TI - [Painful ophthalmoplegia caused by chronic sphenoid sinusitis. Contribution of imaging]. AB - Sphenoid sinusitis is a rare, often misdiagnosed, potentially lifethreatening infection. We report two cases of chronic sphenoid sinusitis presenting as painful ophthalmoplegia. We emphasize the difficulty of the diagnosis due to the deep-seated position of the cavity. The availability of CT and MRI should allow an early diagnosis. Attention has to be paid to the sphenoid sinus on every cranial image. In the chronic as well as in the acute form, the treatment is an emergency. Surgery procedures should be considered when antibiotics are inefficient. Sphenoid sinusitis must be considered in the diagnosis of painful ophthalmoplegia. PMID- 7863187 TI - [Confrontation at Salpetriere hospital. March 1992. Progressive amyotrophy of the upper limbs in a man with a 24 years course starting at age 29]. PMID- 7863188 TI - [New macrolide antibiotics]. PMID- 7863189 TI - [Open questions about HIV/AZT]. PMID- 7863191 TI - [The professional profiles]. PMID- 7863190 TI - [Not only drugs. Cerebral aging and memory disorders]. PMID- 7863192 TI - [Certain aspects of the relationship between the patient with a heart transplant and the donor's family]. AB - The anonimity of cardiac transplant donors and recipients is protected by law but very often media and the press disclose information that are supposed to be strictly confidential. Aim of the survey was to explore how many cardiac transplant recipients are aware of the identity of the donors, if they had any kind of contact with the family of the donor and their overall opinion on the law that protects anonymity. All the patients who underwent a cardiac transplant in the Bergamo Hospital from 1985 to 1991 were mailed a questionnaire. 152 of 154 questionnaires were returned (two patients had died). Only a minority of subjects 44 (29%) contacted the family of the donor and 36 (86.3%) were still in touch. 50% of the subjects knew the name of the donor; 67% of patients would disclose the information of the identity of the donor only if specifically requested by both parties. The results of the survey stress the importance of the issue of the cardiac transplant patients information, both for the patient and the staff. PMID- 7863193 TI - [Management of asthma in a context of ambulatory pediatrics: relevance and possibility to avoid the problems. Gruppo de lavoro pediatri dell'Abruzzo Basilicata e Puglia]. AB - 41 pediatricians agreed to register on a very simple form, all the cases of children affected by bronchial asthma visited in their clinic during october 1993. The data included basic information related to the therapy prescribed, its duration, a judgement on the efficacy of symptoms control and the main problems encountered with the children and their families. 237 cases were reported (mean age 4.6 year, range 2 months-13 years). 80% of children were monitored by the pediatrician; 47% had allergic reactions. The main drug used for profilaxis is ketotifen, a compound without documented efficacy; the main route for drug administration (especially during acute attacks) is by mouth, instead of by aerosol, evidencing problems in the health education on practical skills. In fact the main problems encountered by doctors are related to the communication with patients and families. This survey represents also a research model for involving health care providers and easily and quickly obtaining a useful, methodologically sound and interesting picture of everyday practice. PMID- 7863194 TI - [Learning of the process of nursing diagnosis by nursing students. An experiment at the San Miniato School]. AB - In order to guarantee the quality of health care, it is necessary that the care focus on patients' needs. This requires that care givers possess diagnostic competency skills that allow them to quickly identify the patients' needs, using suitable methods and instruments. In Italy, the development of diagnostic competency skills is generally overlooked in nursing schools; this is due in part to the lack of applied and experimental educational models in teaching and training. During the 1992-1993 year, a didactic teaching intervention to assist students in the acquisition of diagnostic skills was tested. The sample included all students in the third year class of the San Miniato nursing school. The Zanotti's model "Nursing as a stimulus for health-harmony" was used as framework. The purpose of the research was to test: (a) validity and reliability of a new needs' analysis model; (b) the effectiveness of a didactic method for the acquisition of such a model by the students. Students enhanced their skills in data assessment and shifted from the medical perspective to the nursing perspective in using those data to evaluate the patient's status. PMID- 7863195 TI - [Monitoring of intravenous heparin therapy after thrombolysis. Is management by nurses possible?]. AB - IV heparin is a very common therapy in CCUs. In Udine CCU, after the definition of common guidelines, nurses were experimentally charged to administer and monitor the heparin therapy in myocardial infarction patients. Hemorrhagic complications in thrombolyzed and heparinized patients were analysed. No differences were observed with respect to the frequence of complications between the "control" year 1992 before the experiment of autonomy and the following year 1993 (10/67 vs 16/97, OR: 1.1). It can therefore be concluded that nurses are able to administer and monitor IV heparin therapy autonomously from close medical supervision and guidance. PMID- 7863196 TI - [General structure and common elements of an article (II). List of authors of a scientific article]. PMID- 7863197 TI - [The patient who is nursed at home. From spectator to protagonist]. PMID- 7863198 TI - [Dorsal surface of the forearm. Superficial muscles]. PMID- 7863200 TI - [Nursing process: yes or no?]. PMID- 7863199 TI - [Family structure and a hierarchy of needs. An example of participatory investigation]. PMID- 7863201 TI - [The bedridden rheumatic patient (I)]. PMID- 7863202 TI - [Iodine, an an essential element in child nutrition]. PMID- 7863203 TI - [Open tibial fractures. Treatment using an external fixation device]. PMID- 7863205 TI - [Fighting AIDS from the viewpoint of the families]. PMID- 7863204 TI - [Electrocardiographic changes. Nursing activities]. PMID- 7863206 TI - [Nurses in crisis intervention I., Motivation and professional development]. PMID- 7863207 TI - [Women's program. Effect of socioeconomic inequalities on their coverage]. PMID- 7863208 TI - [Dorsal surface of the forearm. The deep muscles]. PMID- 7863209 TI - [Anxiety: how to manage it]. PMID- 7863210 TI - [Therapy and care of rheumatic patients II]. PMID- 7863211 TI - [Instrument for colostomy]. PMID- 7863212 TI - [Assurance of quality of care. Program for the control of surgical wound infections]. PMID- 7863213 TI - [Hydrocolloid dressings. Wound treatment, using occlusive and semiocclusive means]. PMID- 7863214 TI - [Continuing education. Basic electrocardiographic interpretation]. PMID- 7863215 TI - [We only see what we know. Dominican Republic. Life at the rhythm of foam]. PMID- 7863216 TI - International Conference on the CEA (Gene) Family. Freiburg i.Br., Germany, December 2, 1993. PMID- 7863217 TI - Molecular cloning and expression of carcinoembryonic antigen gene family members. AB - The carcinoembryonic antigen (CEA) gene family consists of approximately 30 genes, of which 17 are transcriptionally active. These genes are tightly clustered on the long arm of chromosome 19. Two main subgroups are distinguishable, one encoding CEA and its classical non-specific cross-reacting antigens (NCAs) and the second encoding the pregnancy-specific glycoproteins (PSGs). The CEA family belongs to the immunoglobulin superfamily. CEA subgroup members are either membrane bound through a glycosyl phosphatidylinositol anchor, or are integral membrane proteins, whereas PSG molecules are secreted from the cell. Despite high sequence similarity, CEA family members reveal variable expression patterns, indicating different functions. Apart from its high expression in various adenocarcinomas, CEA is found in epithelia lining the gastrointestinal tract, in eccrine sweat glands, lung epithelia and testes. The NCAs are often coexpressed with CEA, but are also found in granulocytes. PSGs are coexpressed in syncytiotrophoblast cells of the placenta, submandibular salivary glands and fetal liver, as well as in choriocarcinomas and breast tumours. PMID- 7863218 TI - From genes to proteins: the nonspecific cross-reacting antigens. AB - The existence of nonspecific cross-reacting antigens (NCAs), following their first description by von Kleist, was regarded as a disadvantage for the characterization and determination of carcinoembryonic antigen (CEA) using monoclonal antibodies or antiserum. Nowadays, after identification of a family of genes highly homologous to the CEA gene and some of the corresponding proteins, there is increasing evidence for important roles of these molecules in cell adhesion, bacterial binding, bile acid transport and other functions. For example, rapid up-regulation of the well-established NCAs (NCA-160, NCA-95 and NCA-90) on the surface of neutrophilic granulocytes by different inflammatory agents and the inhibition of binding of these cells to cytokine-activated endothelial cells by antibodies against NCAs are good indications for an important role in granulocyte functions. The presence of a consensus sequence in the cytoplasmic domains of some transmembrane members of the CEA family, which was first described for subunits of signal transduction complexes of the immune system (e.g. B and T cell receptor), also suggests a role in signal transduction. Additionally, using stably transfected cells expressing members of the CEA family, NCAs could be clustered to the 'cluster of differentiation' (CD) CD66a-d, during the recent 5th Leukocyte Typing Workshop. Therefore, further contributions to our knowledge about NCAs can be expected not only from researchers working in the CEA field but also from scientists working with cells of the hematopoietic system. PMID- 7863219 TI - Opposite functions for two classes of genes of the human carcinoembryonic antigen family. AB - The human carcinoembryonic antigen (CEA) family can be divided into two subgroups according to the means of anchorage of member glycoproteins to the cell membrane: glycophosphatidyl inositol (GPI) linkage and transmembrane linkage. The GPI linked members tend to be up-regulated in human tumours, whereas the transmembrane-linked members tend to be down-regulated. Thus the question as to whether the GPI members could be formally considered to function as oncogenes and the transmembrane members as tumour suppressors deserves consideration. Members of both subgroups function in vitro as intercellular adhesion molecules, but the characteristics of this adhesion, including temperature and divalent-cation dependence, differ markedly between the groups. Even the mechanism of intermolecular adhesion appears to differ fundamentally in that GPI-linked CEA CEA binding involves a double reciprocal bonding between two domains, whereas transmembrane-linked biliary glycoprotein (BGP)-BGP binding requires only one domain. Finally, the ectopic expression of CEA in myoblasts can block myogenic differentiation leaving the cells with the ability to divide, while expression of BGP does not affect or may even accelerate myogenic differentiation. These differences in phenotypic effects in vitro thus mirror the differences observed in expression in tumours and support the view that the GPI and transmembrane groups have opposite effects on cells in relation to the malignant phenotype. PMID- 7863220 TI - Carcinoembryonic antigen in staging and follow-up of patients with solid tumors. AB - The presence of a tumor antigen in human colonic carcinomas and their metastases was described about 25 years ago. This antigen, called carcinoembryonic antigen (CEA), is one of the first known tumor markers. Since then, many more have been described, but CEA, determined alone or in combination with others, is still one of the most used. CEA is not organ specific and abnormal values may be found in a wide range of carcinomas, especially those with gastrointestinal involvement. CEA assay should not be used for cancer diagnosis because its sensitivity in patients without cancer metastases is low. In addition, abnormal CEA values may be found in patients with benign diseases. However, the probability of malignancy increases directly with CEA concentration. Its main clinical applications are prognosis, early diagnosis of recurrence and follow-up of patients with carcinomas. In a wide range of malignancies, CEA serum levels are clearly related to tumor stage. Presurgical CEA serum levels are a well-established prognostic factor in colorectal, breast and lung cancer. Patients presenting with increased preoperative CEA serum levels have both a shorter disease-free interval and lower survival than those with normal CEA levels. In the early diagnosis of recurrence, CEA also plays an important role: in about 70-85% of patients with colorectal tumors and in 40-50% with breast cancer, CEA serial increase is the first sign of tumor recurrence. In patients with disseminated tumors, serial determinations are also a useful tool for therapy monitoring: CEA values decrease with effective treatment while stable or increasing values are observed when treatment is not effective. PMID- 7863221 TI - Carcinoembryonic antigen family members as diagnostic tools in immunohistopathology. AB - Following an analysis of the literature, the review concludes that the recent huge increase in our theoretical knowledge of the molecular biology of the CEA family has been accompanied by an adequate practical immunohistological implementation. However, a broader use of CEA as a diagnostic tool has been hampered by variable and conflicting results using polyclonal anti-CEA antibodies and by lack of standardization of immunohistochemical methods and tissue preparation. CEA immunoreactivity has been demonstrated in a variety of normal and neoplastic tissues, but in all sites with positive staining, at least one other author has failed to identify CEA reactivity. CEA can be used as a marker to identify epithelial differentiation; however, this will be helpful in only 1% of cases. The introduction of well-defined monoclonal antibodies against clearly defined epitopes of the CEA family will make the differential diagnosis of tumors easier. PMID- 7863222 TI - Internal image-bearing anti-idiotypic monoclonal antibodies. AB - Five anti-idiotypic (Id) monoclonal antibodies (MAbs) (Ab2) were prepared from a BALB/c mouse immunized with anti-carcinoembryonic antigen (CEA) MAb MA208 (Ab1) in a syngeneic system. These anti-Id MAbs appear to recognize unique idiotopes at the combining site of MAb MA208, because they were specifically reactive with MAb MA208 and showed inhibitory activity against the binding of MAb MA208 to CEA. These MAbs were divided into three groups according to the analysis of anti-anti Id antibodies (Ab3) induced with each anti-Id MAb. Anti-anti-Id MAb M7-625 antiserum (Ab3) reacted with purified CEA in a binding assay and in Western blot analysis, and competed with Ab1 binding to CEA. Furthermore, the binding of anti Id MAb M7-625 to MAb MA208 was inhibited with CEA, indicating that Ab2 mimics the structure of the epitope in CEA which was recognized with Ab1. These serologic findings suggest that anti-Id MAb M7-625 carries the internal image of the antigen. According to the amino acid sequences of complementarity determining region (CDR) 1, 2 and 3 of the MAb M7-625 variable region, homology of amino acid sequences exists between CDR2 in the H chain (5 amino acids of 10) and domain III of CEA (545-554). Seven anti-Id MAbs were then generated using anti-CEA synthetic peptide MAb P1-356 to analyze further the epitope structure of CEA. These anti-Id MAbs were divided into four groups. Serological analyses as described above suggested that among them, anti-Id MAb M315 had an internal image. We therefore prepared anti-anti-Id MAbs using anti-Id MAb M315. Among them, anti-anti-Id MAb 11B2 reacted directly with CEA and competed with MAb P1-356 in the competition assay. In addition, MAb 11B2 stained both cultured CEA-producing cells and colonic cancer tissues, suggesting that MAb 11B2 is Ab1 like Ab3. These MAbs (Ab1 3) will be of use for the structural analysis of the internal image. PMID- 7863223 TI - Carcinoembryonic antigen-transgenic mice: a model for tumor immunotherapy. AB - The tumor marker carcinoembryonic antigen (CEA) is a 180-kD glycoprotein expressed on epithelial cells of the gastrointestinal tract and respiratory organs. It is a member of a large family belonging to the immunoglobulin superfamily. In order to develop a mouse model to study tumor immunotherapy using CEA as a target antigen, we have established mice which are transgenic for the CEA gene. The human CEA transgene maintains its spatiotemporal expression pattern in transgenic mice thus providing a suitable model in which to optimize different immunotherapy approaches, with the advantage that negative side effects due to the presence of CEA in normal tissue can be analyzed. PMID- 7863224 TI - Carcinoembryonic antigen as a target cancer antigen for radiolabeled antibodies: prospects for cancer imaging and therapy. AB - This paper reviews the development of cancer imaging with radiolabeled antibodies to carcinoembryonic antigen and the current status and challenges for cancer therapy with radiolabeled antibodies. Advances in antibody preparations, choice of isotope and labeling methods, as well as imaging methods have resulted in rapid and sensitive radioimmunodetection agents that can affect the management of cancer patients. Radioimmunotherapy faces other problems, but advances in antibody engineering and control of dose-limiting myelotoxicity may result in reproducible clinical responses similar to the encouraging results being obtained in the radioimmunotherapy of lymphomas. PMID- 7863225 TI - Carcinoembryonic antigen: some historical perspectives. PMID- 7863226 TI - Absorption and incorporation into tissue lipids of 3H-arachidonic- and 14C linoleic acid: effects of ethanol in jejunal tissue cultures and in vivo. AB - The effects of ethanol in the rat on the absorption and incorporation of 3H arachidonic (20: 4, n-6) and 14C-linoleic acid (18:2, n-6) into tissue lipids was examined in jejunal tissue cultures in vivo. The pattern of incorporation earlier seen in the small intestine in vivo, ie. a preferential incorporation of 3H-20: 4 in comparison to 14C-18: 2 into phospholipids (PL), particularly phosphatidylethanolamine (PE) and phosphatidylinositol (PI) was seen in the jejunal tissue cultures. 10 mM ethanol slightly decreased the incorporation of 3H 20: 4 into PE and PI, but did not change the partitioning of labelled fatty acids into phospholipids and triacylglycerols (TG). Ethanol (100 mM) decreased the incorporation of both 3H and 14C into both PL and TG and caused a moderate increase in the TG/PL radioactivity ratio. Rats were also infused intraduodenally with either 10% ethanol or saline and given 3H-20: 4 and 14C-18: 2 in Intralipid. Radioactivity of tissue lipids were analysed after 1, 2 and 3 h. Ethanol did not significantly influence the absorption or the retention in small intestine, liver or heart of 3H or 14C, or the time course for the 3H- and 14C lipid radioactivity in serum. The distribution of 3H and 14C between total nonpolar lipids and individual PLs was also similar in the two groups, 3H-20: 4 thus exhibiting the same preferential incorporation into PLs, compared to 14C-18: 2, in both groups. Significant amounts of 3H and 14C appeared in phosphatidylethanol (PEth) of the small intestine, heart and liver, when the tissues from the ethanol-infused animals were stored frozen before extraction. When the tissues were extracted immediately after the experiment, the proportions of 3H and 14C migrating as PEth did not exceed 0.5%. Although sufficient amounts of ethanol and the phospholipase D activity necessary for PEth formation were thus present in the tissues examined, little PEth formation thus occurred during the ethanol infusion. In the ethanol treated group about 1% of the 3H and 14C radioactivity of the small intestine was in ethyl ester. Intraduodenal infusion of 10% ethanol in vivo thus has little acute effects on the metabolism of absorbed 18: 2 and 20: 4 in the intestinal mucosal cells. Formation of some ethyl ester occurs, however. PMID- 7863227 TI - A new automated method for continuous registration of factor VII activation in vitro. Activation is accelerated by the concentration of factor VII and the activity state of the protein. AB - When a plasma sample is exposed to tissue factor, single-chain factor VII (FVII) is gradually converted to the active two-chain form (FVIIa). In the present study, we have constructed a measurement system, which allows continuous registration of the activation of FVII to FVIIa in vitro. In this system, FVII activation follows parabolic kinetic after an initial lag-phase. The slope of the linear phase is a measure of the protein concentration of factor VII (FVIItotal), while the length of the non-linear phase represents the velocity of FVII activation. The time required for complete activation of FVII is inversely related to both FVIItotal and the relative amount of FVIIa in the sample. In future studies, this new measurement system will make it possible to study the process of FVII activation in different samples, and to examine how varying concentrations of exogenous added components affect the activation process in vitro. PMID- 7863228 TI - Different types of heparin in haemodialysis: long-term effects on post-heparin lipases. AB - Several long-term studies of haemodialysis patients have shown improved serum lipid profile associated with treatment with low molecular weight heparin (LMWH) as compared with unfractionated heparin (UH). This has been attributed to the fact that LMWH produces a less marked acute lipolytic response than UH. However, the information on the differences in long-term effects on tissue releasable lipases is limited. Post-heparin plasma lipase activities were measured at 6, 24 and 48 h after pre-dialysis heparin injections in seven patients on chronic haemodialysis during treatment with UH; these measurements were then repeated 2 and 6 months after treatment was switched to LMWH. The curves plotted from the results can be assumed to reflect the interdialytic lipolytic potential. In the case of lipoprotein lipase this was unchanged 2 months after treatment was switched from UH to LMWH but increased by a mean of 47% after 6 months. In the case of hepatic lipase there was no change in the interdialytic lipolytic potential. Thus, there was a slow increase in tissue releasable lipoprotein lipase stores after treatment was switched from UH to LMWH, probably reflecting a smaller loss of lipoprotein lipase after each LMWH injection. Hepatic lipase, in contrast, was not affected by the type of anticoagulation. PMID- 7863229 TI - Effects of indomethacin on renal function in normotensive patients with chronic glomerulonephritis with preserved renal function. AB - Thirteen normotensive patients with biopsy verified chronic glomerulonephritis (GN) with preserved renal function and 12 healthy control subjects (CS) were studied before and during prostaglandin synthesis inhibition by indomethacin. Glomerular filtration rate (GFR), renal plasma flow (RPF), urinary output (V), sodium excretion (UNa V), fractional lithium excretion (FELi), plasma levels of angiotensin II (Ang II), aldosterone (Aldo), atrial natiuretic peptide (ANP), arginine vasopressin (AVP) and endothelin (ir-ET) and urinary excretion rates of PGE2, mean blood pressure (MBP) and heart rate (HB) were determined on two separate occasions at least 7 days apart. During basal conditions without indomethacin administration no significant differences were found between the two groups. Indomethacin administration (100 mg 12 h and 1 h before clearance investigations) resulted in significant and almost identical decreases in GFR, RPF, V, UNa V, FELi and HR and increases in MBP in both the GN group and the CS group. It is concluded that normotensive patients with a biopsy verified chronic glomerulonephritis but with preserved renal function and without nephrotic syndrome have no increased risk of acute deterioration of renal function during administration of a non-steroidal anti-inflammatory drug compared with healthy control subjects. PMID- 7863230 TI - Parathyroid hormone in blood pressure and volume homeostasis in healthy subjects, hyperparathyroidism, liver cirrhosis and glomerulonephritis. A possible interaction with angiotensin II and atrial natriuretic peptide. AB - In order to elucidate a participation of intact parathyroid hormone (PTH(1-84)) in blood pressure (BP) and body fluid homeostasis, we studied fluctuations of PTH(1-84) during manipulations of BP in hyperparathyroid and healthy subjects, and during manipulations of blood volume in patients with glomerulonephritis or liver cirrhosis and in controls. Angiotensin II induced BP elevation was associated with increased values of PTH(1-84) both in healthy subjects (12-25 ng l-1, medians, p < 0.01), in patients with primary hyperparathyroidism (94-125 ng l-1, p < 0.01), in patients with low calcium due to end stage renal disease before requirement of dialysis (95-151 ng l-1, p < 0.02), and in patients with tertiary hyperparathyroidism (221-264 ng l-1, p < 0.05), but not in dialysis patients without hypercalcaemia (126-174 ng l-1, NS). The changes could not be attributed to reduction of serum calcium, but probably to the increase of plasma angiotensin II, which was positively correlated to the increase of serum PTH(1 84) in the healthy subjects (p = 0.619, n = 15, p < 0.05) and in the patients with primary hyperparathyroidism (p = 0.549, n = 18, p < 0.05). Noradrenaline induced BP elevation did not have a similar effect on PTH(1-84), and changes of PTH(1-84) were not related to changes of BP. Volume depletion after furosemide injection, also accompanied by increased levels of angiotensin II, resulted in elevation of PTH(1-84) in controls, cirrhotics, patients with glomerulonephritis without the nephrotic syndrome, but not in nephrotic patients. Volume depletion induced by bolus injection of atrial natriuretic peptide (ANP) was associated with decreased PTH(1-84) in healthy subjects (20-18 ng l-1, p < 0.02), but not in patients with nephrotic syndrome and liver cirrhosis. Volume expansion induced by albumin infusion caused increased plasma levels of ANP, but PTH(1-84) was unaltered. Thus, angiotensin II may be able to stimulate, and ANP to inhibit release of PTH(1-84), and PTH(1-84) may be involved in the regulation of BP and body fluid homeostasis. BP changes or changes in blood volume per se do not seem to influence PTH(1-84) levels. PMID- 7863231 TI - The influence of N-acetylcysteine on the measurement of prothrombin time and activated partial thromboplastin time in healthy subjects. AB - The purpose of the study was to evaluate whether the infusion of N-acetylcysteine decreased the measurement of prothrombin time and activated partial thromboplastin time (APTT) in healthy persons. N-acetylcysteine was administered intraveneously 10 mg kg-1 as a loading dose and then at a rate of 10 mg kg-1 h-1 for 32 h in six male subjects. The intrinsic, extrinsic and common pathway of coagulation were monitored with activated partial thromboplastin time (APTT), and prothrombin time, respectively. In addition, the extrinsic coagulation pathway was monitored with the clotting activity of single factors II, VII, and X. No effect on the intrinsic coagulation pathway was observed. There was a significant and rapid decrease in prothrombin time. Coagulation factors II, VII and X, the three components of prothrombin time, decreased significantly to different degrees. We conclude that infusion of N-acetylcysteine intraveneously decreases the prothrombin time in healthy subjects. Thus, one should not make conclusions which are too far-reaching based on prothrombin time alone in patients who have been treated recently with N-acetylcysteine intraveneously. PMID- 7863232 TI - Effects of free fatty acids found increased in women who develop pre-eclampsia on the ability of endothelial cells to produce prostacyclin, cGMP and inhibit platelet aggregation. AB - Recently, we showed that levels of circulating free fatty acids are increased in women who later develop pre-eclampsia long before the clinical onset of the disease. Among the serum free fatty acids, oleic-, linoleic-, and palmitic acid were found to be increased by 37, 25 and 25%, respectively. In the present study we asked if these free fatty acids can interfere with endothelial cell functions. Cultured endothelial cells were exposed to linoleic-, oleic- and palmitic acid in concentrations ranging from 0.016 to 0.133 mumol ml-1, resulting in molar ratios of free fatty acids to albumin of 0.2-1.6. We found that among these fatty acids, linoleic acid reduced the thrombin-stimulated prostacyclin release by 30-60%, oleic acid by 10-30%, whereas palmitic acid had no effect. Endothelial cells incubated in presence of linoleic acid showed a concentration-dependent reduction in prostacyclin release in response to thrombin, and cells incubated with linoleic acid for up to 28 h, showed a reduced thrombin-induced prostacyclin release at every time point. Endothelial level of cGMP mainly reflected the synthesis of endothelium-derived relaxing factor/nitrogen monoxide (EDRF/NO), since blocking of the endogenous production of EDRF/NO with N-omega-nitro-L arginine, resulted in about 90% reduction in cGMP-content of the endothelial cells. Incubation with linoleic acid reduced the endothelial cGMP level by 70%. Linoleic acid reduced the endothelial cells ability to inhibit platelet aggregation by 10-45%, (p = 0.0019). It was concluded that linoleic acid impedes the ability of the endothelial cells to produce prostacyclin and cGMP, and to inhibit platelet aggregation. PMID- 7863233 TI - The behaviour of lipoprotein(a) in patients with various diseases. AB - The plasma Lp(a) concentrations were evaluated in several groups of patients. Groups with liver cirrhosis (n = 20), type-1 diabetes mellitus (n = 148), type-2 diabetes mellitus (n = 65), hypertension (n = 51), lung cancer (n = 48) and deep venous thrombosis (n = 31) were compared with a group of healthy volunteers (n = 69). Significantly higher median values were found in the hypertension (142 mgl-1 vs. 43 mgl-1, p < 0.001) and lung cancer groups (241 mgl-1 vs. 43 mgl-1; p < 0.0001). Significantly lower values were recorded in the group with liver cirrhosis (11 mgl-1 vs. 43 mgl-1; p = 0.02). But in this last group there were significant differences between patients in the Child-Turcotte severity stages A to C. PMID- 7863234 TI - The estimated free concentration of calcidiol is higher in venous cord blood than in maternal blood. AB - The serum levels of calcidiol (25-hydroxy-vitamin D3), calcitriol (1,25-dihydroxy vitamin D3), albumin and vitamin D-binding protein (DBP) were measured in venous cord blood and in maternal blood at delivery. These results were used to calculate the free concentrations of calcidiol and calcitriol in maternal and fetal blood. Fifty three women participated in the study. Seventeen of the participants were excluded from the calculations because their calcidiol levels were below the limit of detection (< 5 nmoll-1). The estimated free concentration of calcidiol was on average 26% higher in cord serum than in maternal serum, the mean difference being 1.1 pmoll-1 (p = 0.001). The estimated free concentration of calcitriol, however, was 21% lower on the fetal side (p < 0.001). The difference was small, the mean value being 0.07 pmoll-1. A strong positive association existed between the serum levels of free calcidiol (r = 0.82, p < 0.001) and free calcitriol (r = 0.83, p < 0.001) in maternal blood and cord blood. PMID- 7863235 TI - Helicobacter pylori phenotypes associated with peptic ulceration. AB - Persistent infection with Helicobacter pylori occurs in a large percentage of the population, particularly in countries with low socioeconomic status. Such infection nearly always produces chronic gastric inflammation, although in most individuals it is clinically silent and only a minority of infected persons develop H. pylori-induced peptic ulcers. In this review, the hypothesis that diversity among H. pylori strains is at least partly responsible for the observed variability in the outcome of infection is explored. To date, four phenotypes that vary among H. pylori strains have been identified: variations in lipopolysaccharide structure; expression of the cagA-encoded product; production of a vacuolating cytotoxin, and enhanced activation of neutrophils. These phenotypes are associated with one another, with enhanced tissue inflammation, and with peptic ulceration, suggesting that H. pylori strain characteristics have an important influence on the clinical outcome of H. pylori infection. PMID- 7863236 TI - Helicobacter pylori in Peptic Ulcer Disease. Proceedings of a symposium. Brussels, Belgium, 23 September 1993. PMID- 7863237 TI - Epithelial cytotoxicity, immune responses, and inflammatory components of Helicobacter pylori gastritis. AB - To clarify the mechanisms of the gastric mucosal immune--inflammatory response to Helicobacter pylori infection, surgical and biopsy specimens from asymptomatic uninfected, gastritis-free individuals and from H. pylori-positive ulcer patients with chronic gastritis were investigated using light and electron microscopy. Activation of the antigen-transporting endocytic--endosomal system, enhanced expression of the antigen-processing enzyme cathepsin E and de novo expression of antigen-presenting human leukocyte antigen (HLA)-DR molecules have been detected in H. pylori-colonized gastric epithelium. These findings may be crucial in the production of a mucosal immune-inflammatory response to H. pylori infection. Cytoplasmic swelling and vacuolation, micropapillary change, mucin loss, erosion of the juxtaluminal cytoplasm and cell desquamation were the main effects of bacterial cytotoxicity on gastric surface-foveolar epithelium. Activated macrophages and granulocytes (partly linked to the mucosal IgG immune response) concentrate in the foveolar-neck region of the mucosa, where they may enhance damage and impair regeneration of the epithelium. Both direct bacterial cytotoxicity and inflammatory cell aggression against gastric epithelium may predispose the patient to peptic ulcer disease. PMID- 7863238 TI - The role of the local immune response in the pathogenesis of peptic ulcer formation. AB - Mucosal immune responses are designed to provide local protection against infection, without inducing excessive amounts of inflammation that would alter epithelial integrity or function. It has become clear that the epithelium not only serves as a barrier to exclude pathogens, but also initiates host responses to infection. Gastric epithelial cells infected with Helicobacter pylori can respond within hours to produce inflammatory mediators that recruit and activate neutrophils. The gastric epithelium can also be recognized by local T-cells, resulting in their activation and ability to induce epithelial damage. During infection with H. pylori, there is a remarkable increase in the level of local IgG antibodies, which may also recognize and damage the epithelium. Thus, activated neutrophils, T-cells and auto-antibodies may contribute to a weakened epithelial barrier that allows luminal acid and other factors to contribute to peptic ulceration. The epithelium appears to play a key role in the initiation of the local inflammatory and immune responses that may contribute to the more serious sequelae associated with H. pylori infection. PMID- 7863239 TI - The role of omeprazole and antibiotic combinations in the eradication of Helicobacter pylori--an update. AB - When omeprazole is given with an appropriate antibiotic, a high rate of Helicobacter pylori eradication can be achieved. To date, most studies have used omeprazole and amoxycillin, and an analysis of the results suggests that, at present, the most effective treatment regimen comprises omeprazole, 20 mg twice daily, and amoxycillin, 1 g twice daily, for 14 days. This regimen provides an eradication rate of about 85%. Results using omeprazole plus bismuth or tetracycline have been disappointing; however, preliminary studies of omeprazole plus clarithromycin show promise, although further data are needed. Treatment with omeprazole plus two different antibiotics has also been used in a number of studies. The results thus far have been variable, although increases in the omeprazole dose/regimen might improve eradication rates. Moreover, one recent study that used omeprazole, a low dose of clarithromycin and tinidazole gave 100% H. pylori eradication after 1 week. If the effectiveness of this regimen is confirmed, it will prove to be the most effective treatment for the eradication of H. pylori identified to date. PMID- 7863240 TI - Long-term consequences of Helicobacter pylori eradication. AB - Long-term infection with Helicobacter pylori could potentially lead to asymptomatic chronic gastritis, chronic dyspepsia, duodenal ulcer disease, gastric ulcer disease, or gastric malignancy, including both adenocarcinoma and B cell lymphoma. Currently, the two most important indications for eradication of this bacterium are proven H. pylori-associated duodenal or gastric ulcer disease. Many studies have shown that successful eradication of H. pylori dramatically reduces the rate of duodenal ulcer relapse, and long-term follow-up data appear to support the claim 'no H. pylori, no gastritis; no gastritis, no ulcer', which follows on from the old, but certainly valid, dictum 'no acid, no ulcer'. Furthermore, absence of relapse parallels the marked improvement in gastric histology (e.g. regression of gastritis). Whether there is concomitant regression of gastric metaplasia in the duodenal bulb is, however, controversial. Despite the rather limited data for H. pylori-associated gastric ulcer, successful eradication of the organism has been equated with cure of peptic ulcer disease. Again, eradication parallels a substantial improvement in gastric histology. Although eradication of H. pylori is not currently recommended in asymptomatic individuals or dyspeptics, it has been well documented in previous studies that successful eradication improves the gastric histology in patients with H. pylori associated dyspepsia. From these studies, it appears that the disappearance of polymorphs from the inflammatory infiltrate occurs rather rapidly after eradication, although regression of the mononuclear component of the inflammatory reaction is more prolonged. PMID- 7863241 TI - Treatment strategies for symptom resolution, healing, and Helicobacter pylori eradication in duodenal ulcer patients. AB - The introduction of anti-Helicobacter pylori therapy has increased the number of options available for the management of patients with duodenal ulcer disease. The aim of this paper is to summarize current knowledge and use it to form a strategy relevant to the management of patients with duodenal ulcer disease. Four key aspects are addressed. (i) Selection of duodenal ulcer patients for anti-H. pylori treatment. As the subgroup of patients who will develop minor disease activity in the future cannot be identified with sufficient precision, and the therapeutic gain achieved by curing H. pylori infection is significant, all patients with duodonal ulcer and H. pylori infection should receive eradication therapy. (ii) Confirmation of H. pylori infection before eradication. A diagnostic test confirm H. pylori infection is useful in identifying the small group of H. pylori-negative duodenal ulcer patients with nonsteroidal anti inflammatory drug (NSAID)-induced ulcer or Zollinger-Ellison syndrome. (iii) Choice of treatment. This should be based on efficacy of eradication, rate of ulcer healing and symptom resolution, adverse effects profile, simplicity and cost. At present, there are four effective eradication therapies documented: omeprazole plus amoxycillin or clarithromycin; omeprazole, amoxycillin and metronidazole; 'classic' triple therapy (bismuth, amoxycillin (or tetracycline) and metronidazole); and ranitidine, amoxycillin and metronidazole. (iv) Confirmation of eradication after treatment. This is needed in cases in which the chosen therapy has an efficacy below 80-90%. The test is important to identify those patients who require repeated treatment, before they present with an ulcer relapse. PMID- 7863242 TI - Future research in peptic ulcer disease. AB - For the past 10 years, research into peptic ulcer disease has focused on the surprising suggestion that gastritis and peptic ulcers may be caused by the bacterium Helicobacter pylori. However, the time has now come to reappraise research directions, as a causal link has been established, and even the most ardent sceptics now accept that H. pylori infection is the major factor in most cases of peptic ulcer disease. As with any established microbial disease, we need to understand the epidemiology and mechanisms of pathogenesis, but the major focus should be towards improving therapies and defining the long-term outcome of H. pylori eradication. To devise novel therapeutic agents effectively, we must increase our knowledge of the basic physiology of H. pylori and its ecology in the stomach. This has been a surprisingly neglected area of research and major questions remain. Why does the organism flourish in different areas of the gastric mucosa when gastric pH is increased? Is a change in pH the reason for the potentiating effects of acid-inhibitory agents on anti-H. pylori activity? Will knowledge of the host and bacterial factors that initiate ulcerogenesis allow us to better predict H. pylori-associated ulcers by using non-invasive methods? As H. pylori is a major gastroduodenal pathogen, can we eliminate the infection from selected populations? What are the criteria that will allow therapeutic intervention? The first steps have been taken in the development of an effective vaccine, but who should be immunized?(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863243 TI - Helicobacter pylori eradication: the rational treatment for peptic ulcer disease- chairmen's conclusion. PMID- 7863244 TI - Are there susceptible hosts to Helicobacter pylori infection? AB - Susceptibility to Helicobacter pylori infection may manifest itself as an increased prevalence of H. pylori infection, as reinfection after eradication, or as different clinical outcomes (gastritis, peptic ulcer disease, primary gastric B-cell lymphoma, or gastric cancer). These outcomes are likely to be a result of interaction between environmental and genetic factors. Genetic factors include both host genetic predisposition to infection as well as genetic differences in H. pylori strains. Twin studies indicate that the correlation coefficient for the relative importance of genetic effects (heritability) on acquisition of H. pylori infection is approximately 0.66. The remaining variance is accounted for by shared rearing environmental factors (20%), and non-shared environmental factors (23%), which contribute to the differences and not the similarities seen between family members. Molecular epidemiological studies of both the whole bacterial genome and of amplified regions between specific repetitive DNA sequences also suggest that there are disease-specific strains of H. pylori. There are, therefore, many different facets of susceptibility to H. pylori infection. PMID- 7863245 TI - Nizatidine: a clinical up-date, including a quality of life perspective. Proceedings of a meeting in London, United Kingdom, October 1993 and a symposium in Marrakech, Morocco, January 1993. PMID- 7863246 TI - Drug interactions of H2-receptor antagonists. AB - Three drug interactions of nizatidine and of other antisecretory agents were studied comparatively. First, the effects of nizatidine, cimetidine and ranitidine on the dispositional kinetics of theophylline were evaluated in chronic obstructive pulmonary disease (COPD) patients. Second, the effect of magnesium/aluminium hydroxide on the relative bioavailability of nizatidine, famotidine, cimetidine and ranitidine was evaluated in healthy volunteers. Finally, the effects of nizatidine and omeprazole on the dispositional kinetics of phenytoin were evaluated in healthy volunteers. Only cimetidine altered the steady-state kinetics of oral theophylline, slowing theophylline clearance by 25%. Each of the H2-receptor antagonists exhibited a modest decline in relative bioavailability when ingested with antacid. Antacid ingestion decreased the bioavailability of famotidine, ranitidine and cimetidine by 20-25%, and the bioavailability of nizatidine by 12%. Each of these effects was statistically significant. Finally, it was found that neither omeprazole nor nizatidine affected the single dose kinetics of phenytoin. PMID- 7863247 TI - Histologic patterns of omeprazole and nizatidine-healed duodenal ulcers:accuracy of endoscopic diagnosis. AB - The mechanisms underlying duodenal ulcer (DU) recurrence after endoscopically confirmed healing are unclear. We sought to examine histologic differences in healing induced by omeprazole and nizatidine. This also entailed assessing interobserver variation in endoscopic diagnosis and the correlation between endoscopic and histomorphologic healing. We treated 31 DU patients for 4 weeks with either omeprazole (20 mg daily a.m.) or nizatidine (300 mg twice daily). The healing rates of both groups showed no significant differences (86.7% versus 81.2%; p = 0.5). Good mucosal repair rates did not differ significantly (38.5% versus 69.2% respectively; p = 0.5). Endoscopists' agreement over scar type was 0.80, with the chance of agreement 0.70 (k = 0.34 +/- -0.08). The correlation between macroscopic and histologic appearance of scars was fair, but fully significant (r = 0.48; p < 0.05). We conclude that the study was too small to detect significant differences in healing patterns between the two drugs. The wide variation in endoscopic diagnosis suggests that mucosal repair is best assessed by histologic examination of biopsy samples. PMID- 7863248 TI - Nizatidine in therapy and prevention of non-steroidal anti-inflammatory drug induced gastroduodenal ulcer in rheumatic patients. AB - Two hundred and sixty-nine patients with various rheumatic disorders who had been treated with non-steroidal anti-inflammatory drugs (NSAID) for at least 3 weeks were enrolled in this randomized double-blind multicentre trial. Entry criteria were the presence of an ulcer in the gastric and/or duodenal mucosa (> 3 mm and < 20 mm in diameter) and dyspeptic symptoms. The patients were treated with 150 mg nizatidine nocte (n = 86), 2 x 150 mg/d (n = 93) and 2 x 300 mg/d (n = 90) nizatidine. All patients continued to take their original NSAID medication. The three nizatidine groups were well matched with respect to important patient characteristics. After 8 weeks of treatment more than 90% of gastric and duodenal ulcers (DU) had healed under all three nizatidine dosages. There was a tendency to higher healing rates in the case of gastric ulcers after 4 weeks following the higher dose of nizatidine. Erosion, in the stomach and duodenum as well as oesophagitis, improved to a similar degree with all nizatidine doses. There were similar improvements in clinical symptoms such as epigastric pain, heartburn etc. Consumption of additional antacids were similar in all three groups. In the subsequent prevention trial, 237/221 patients were followed for 3/6 months. In addition to their continued antirheumatic medication 116/107 received nizatidine 150 mg nocte and 121/114 patients 2 x 150 mg nizatidine daily. The cumulative relapse rates within 6 months averaged 5.5% in the low and 1.8% in the high dose group (NS). The safety of nizatidine was assessed as good in both the therapeutic and the preventive trial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863249 TI - Continuous infusions of nizatidine are safe and effective in the treatment of intensive care unit patients at risk for stress gastritis. The Nizatidine Intensive Care Unit Study Group. AB - This multicentre, randomized, parallel, double-blind study compared the safety and efficacy of nizatidine 20 and 10 mg/h with placebo. The objective was to maintain gastric pH > 4 in seriously ill patients at risk for stress gastritis. Gastric aspirate was obtained at 2-h intervals through a nasogastric tube after beginning study drug, and tested for pH and the presence of blood. Antacid doses (15 ml per dose) were individually adjusted and administered whenever the gastric pH was < 4. Significant gastrointestinal bleeding was assessed clinically by Hemmocult results, presence of frank bleeding from the GI tract, number of transfusions and vital signs. One hundred and twenty-six patients, 43 nizatidine 20 mg/h, 43 nizatidine 10 mg/h and 40 placebo were admitted to the study. For the treatment period, patients treated with either dose of nizatidine required significantly less antacid than placebo treated patients to maintain gastric acid pH > or = 4 (median total: 45 ml versus 180 ml, p < 0.001). Adverse clinical and laboratory events were similar or less frequent in the nizatidine groups compared with placebo. Nosocomial pneumonia occurred with very low frequency in all treatment groups. PMID- 7863250 TI - Acid inhibitory characteristics of nizatidine in man: an overview. AB - The antisecretory activity of nizatidine, an H2-receptor antagonist, has been extensively investigated in man both by quantitative acid secretory tests and by means of 24-h continuous ambulatory pH monitoring. Studies have shown that nizatidine is a potent inhibitor of basal, nocturnal and stimulated acid secretion. Particular modalities of nizatidine administration, such as early evening intake with supper or morning dosing, have been recently defined. Further studies are needed to clarify if rebound nocturnal acid hypersecretion may develop after abrupt withdrawal of nizatidine or if tolerance may develop during prolonged administration. PMID- 7863251 TI - Quality of life in gastroenterology. Interest of a specific questionnaire for duodenal ulcer patients. AB - Quality of life (QoL), a subjective dimension, should be the most important criterion in the management of any disease. However, relevant methods have not been widely adopted although a large number of general health assessment measures are available. A consensus has now been reached on the importance of five domains: physical, mental, social and role functioning, and general health perception. Questionnaires are generally accepted as convenient tools, particularly when they include an assessment of general health and disease specific questions. In gastroenterology, chronic disease (e.g. Crohn's disease) and prolonged discomforts are ideal fields for QoL studies, and QoL data should be obtained in therapeutic trials. In duodenal ulcer (DU), the long-term nature of treatments and psychological status of patients make QoL studies of major interest, as exemplified by the nizatidine model. PMID- 7863252 TI - A 'quality of life questionnaire' adapted to duodenal ulcer therapeutic trials. AB - In order to compare subpopulations of duodenal ulcer (DU) patients a quality of life (QoL) questionnaire (self-administered) was developed with the objective of investigating: (i) general parameters of health and well-being, and (ii) dimensions specifically adapted to patients with DU. For the former, Ware's MOS SF-36 was selected as a central core, with 36 items investigating 9 dimensions, and for the latter the anxiety scale (5 items) of the Psychological General Well being Index (PGWBI) questionnaire and a further 5 dimensions (13 items) resulting from a preliminary survey of ulcer patients were selected. Validation of the proposed questionnaire was obtained for: linguistic aspects, content (i.e. ability to cover problems of patients suffering from DU), internal consistency, reliability, and sensitivity (i.e. analysis of discrimination between three groups of patients (acute DU episode, remission and control). The final version of the Quality of Life in Duodenal Ulcer Patients (QLDUP) questionnaire, which includes 54 items investigating 15 dimensions, appears to be a sensitive and reproducible tool, the simplicity of which makes it suitable for monitoring long term treatments in DU. PMID- 7863253 TI - A quality of life study in five hundred and eighty-one duodenal ulcer patients. Maintenance versus intermittent treatment with nizatidine. AB - Quality of life (QoL) is commonly assessed for evaluating the process and outcome of treatment but has not been studied in duodenal ulcer (DU) disease. The recently developed and validated Quality of Life in Duodenal Ulcer Patients (QLDUP) questionnaire allowed the study of various dimensions according to treatment regimens. This study was conducted to compare QoL over a one-year follow-up period in DU patients randomized to two treatment regimens: maintenance versus intermittent (no maintenance) treatment with nizatidine. A total of 581 patients with endoscopic evidence of DU healing were randomly allocated to receive either nizatidine 150 mg/day for one year (Group A) or intermittent treatment (Group B). In both groups, symptomatic relapses were treated with nizatidine 300 mg/day for 6 weeks. The QLDUP questionnaire, which provides a QoL profile from 54 items divided up into 15 dimensions, was completed by all patients at entry and again at the time of a visit every 2 months for one year. The one-year symptomatic relapse rates were 8.0% and 33.5% in Group A and Group B, respectively (p < 0.001). The intent-to-treat analysis showed that patients in Group A had better QoL scores than those in Group B as regards 8 QoL dimensions, including ulcer-specific and non-specific dimensions. Differences between treatments were significant after 4 months, and this was sustained until the one year assessment. The overall gain in QoL was significantly greater in Group A than in Group B with respect to 11 QoL dimensions. In conclusion, maintenance treatment with nizatidine for DU improved QoL to a larger extent than when intermittent therapy was used. PMID- 7863254 TI - Nizatidine as maintenance treatment of duodenal ulcer. Clinical results. AB - In assessing treatments for chronic diseases such as duodenal ulcer (DU), measuring the patient's quality of life (QoL) is as important as objective measures of treatment efficacy. This study was part of a larger study assessing the QoL of patients with DU treated with nizatidine. The aim of this part of the 12-month study was to assess the clinical efficacy and the influence of maintenance therapy with nizatidine on the long-term treatment of patients with healed DU. The trial, which was open, randomized and controlled, was conducted in 177 centres throughout France. A total of 581 patients of 18 years or over with endoscopically confirmed DU were assigned to two groups. The active treatment group received nizatidine 150 mg/day for one year and the control group had no regular treatment. Both groups had free access to antacid tablets, use of which was recorded. Symptomatic relapse was treated with nizatidine 300 mg/day for 6 weeks. Clinical assessments were made every 2 months, at which times patients also recorded their symptoms. The relapse rate in the nizatidine-treated group was significantly lower than in the control group at 6 months (4.5% versus 15.3%; p < 0.0001). At 12 months the difference was still significant (8.0% versus 33.5%; p < 0.001). Antacid consumption was significantly greater in controls than in the nizatidine-treated group (44.7% versus 29.7%; p < 0.001). It is concluded that nizatidine is a safe and effective therapy for preventing DU recurrence in patients with endoscopically confirmed healed ulcers. PMID- 7863255 TI - Effect of nizatidine versus ranitidine on gastric intraluminal prostaglandin release in duodenal ulcer patients. AB - The role of prostaglandins in peptic ulcer disease and their relation to Helicobacter pylori infection remain controversial. This study sought to compare the effects of oral nizatidine and ranitidine on the gastric mucosal release of prostanoids in duodenal ulcer (DU) patients and to correlate prostanoid concentrations with H. pylori status. Twenty-eight patients with DUs were randomized to receive either nizatidine or ranitidine. Nizatidine 300 mg at night elevated intraluminal PGE2 concentrations; 6-keto-PGF1 alpha concentrations also rose, but did not reach statistical significance. Ranitidine induced non significant falls in PGE2 and 6-keto-PGE1 alpha concentrations. Patients with H. pylori infection had lower PGE2 and 6-keto-PGF1 alpha concentrations than non infected patients, but nizatidine was equally effective in increasing prostanoid levels in both groups. These findings may be considered as favourable side effects of nizatidine with uncertain clinical significance. Further studies are needed to elucidate the synergism between prostanoids, eradication of H. pylori and nizatidine in the treatment of DU. PMID- 7863256 TI - Regional specialization of intraepithelial T cells in the murine small and large intestine. AB - We investigated intraepithelial T cells from the small intestine, SI (jejunum, ileum) and the large intestine, LI (colon) of euthymic (BALB/c, H-2d; C.B-17+/+, H-2d; C57BL/6, H-2b) and athymic (C57BL/6 nu/nu; BNX bg/bg nu/nu xid/xid) mice. From individual euthymic and athymic mice, 7 x 10(6) intraepithelial lymphocytes (IEL) per mouse were isolated from the SI. Ten-fold lower numbers of IEL were obtained from the LI epithelium (4 x 10(5) IEL per mouse). Thymus-dependent and independent T cells represented > 80% of SI-IEL but the fraction of T cells was reduced from 20% to 40% in LI-IEL. In euthymic mice, alpha beta T cells predominated in SI-IEL and in particular in LI-IEL populations, while SI-IEL and LI-IEL populations of athymic mice contained predominantly gamma delta T cells. The intraepithelial T cell subset distribution was different in SI versus LI: mainly CD8+ T cells were present in the SI, but a large CD4+ T cell subset was present in the LI. 'Double positive' CD4+ CD8 alpha+ T cells were present mainly in the SI epithelium but were rare in the LI epithelium. In euthymic as well as athymic mice, T cells expressing the homodimeric CD8 alpha alpha isoform predominated in the SI epithelium, while T cells expressing the heterodimeric CD8 alpha beta isoform predominated in the LI epithelium. LI-derived TCR alpha beta+ IEL displayed the CD2+ CD28+ LPAM-1/2- M290+ phenotype, and a fraction of them expressed the L-selectin LECAM-1. In contrast, a large fraction of TCR alpha beta+ SI-IEL was CD2- CD28- LPAM-1/2- M290+ and LECAM-1-. RAG-1/2 expression was detectable by RT-PCR in IEL from the SI but not the LI. Striking differences in phenotype were thus apparent between thymus-dependent and thymus-independent T cells in the epithelial layer of the jejunum/ileum and the colon of the mouse. PMID- 7863257 TI - Three-colour flow cytometric immunophenotyping in HIV-patients; comparison to dual-colour protocols. AB - Flow cytometric measurement of circulating CD4+ lymphocytes is important in the evaluation of disease progression in HIV-infected patients. Development of dyes that can be exited at 488 nm and have emission maximum in the far red area has made three-colour protocols, together with fluorescein isothiocyanate (FITC) and R-phycoerythrin (PE), possible in most clinical flow cytometers. We report here the comparison of a two-tube, three-colour protocol (including CD45/CD4/ CD3 and CD8/CD4/CD3) with our conventional dual-colour protocol. No significant differences were found between percentage of CD3+ lymphocytic cells determined with three different antibody combinations. When the CD8/CD4/CD3 combination was used a systematic overestimation of CD3+ CD4+% cells was found. This turned out to be caused by the formation of 'CD8-escapees'. These are clumps of CD8+ cells that fall outside the lymphocyte gating region, principally because of high side scatter. The problem can be overcome by rigorous vortexing to loosen aggregates. The lymphocyte gating principle used in this protocol (gating on a side scatter/CD45 dot plot) is readily applicable to other antibody combinations. This was demonstrated by measuring CD5+ B lymphocytes, a subset receiving increasing attention in the study of HIV-induced immune deviations. We conclude that our three-colour protocol for CD4+ T-lymphocyte determinations offers significant advantages to the conventional dual-colour method, and we suggest that when possible anti-CD45 be added to dual-colour combinations in order to improve lymphocyte gating. PMID- 7863258 TI - Interferon-alpha production and tissue localization of interferon-alpha/beta producing cells after intradermal administration of Aujeszky's disease virus infected cells in pigs. AB - Intradermal administration of glutaraldehyde-fixed Aujeszky's disease virus (ADV) infected autologous or allogeneic cells resulted in the induction of an interferon (IFN)-alpha response in pigs. Using a sensitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA), IFN-alpha was detected in blood at 8 and 24 h after injection of ADV-infected cells. In parallel, by means of in situ hybridization, IFN-alpha/beta mRNA containing cells were demonstrated in regional lymph nodes. Occasional IFN-alpha/beta mRNA positive cells were also seen in injected dermal areas, but not in contralateral lymph nodes, spleen, bone marrow, blood or liver. The ability of leucocytes in whole blood cultures to produce IFN alpha upon stimulation by ADV was markedly diminished 3-7 days after intradermal injection of ADV-infected cells. In contrast, cultures of purified peripheral blood mononuclear cells (PBMC) had intact IFN-alpha responses. Further, serum from ADV-injected pigs inhibited the in vitro ADV-induced IFN-alpha responses in PBMC from control pigs, most likely due to the demonstrated presence of anti-ADV antibodies. We suggest that the IFN-alpha/beta producing cells in lymph nodes may participate in the development of antiviral immunity and could be equivalent to Natural IFN-alpha/beta producing (NIP) cells. PMID- 7863259 TI - IgG2 deficiency associated with defects in production of interferon-gamma; comparison with common variable immunodeficiency. AB - We report a novel mechanism of IgG2 deficiency. Several investigators have reported patients with IgG subclass deficiencies due to homozygous deletion of immunoglobulin heavy chain constant region genes. However, it is unclear what mechanism is responsible for IgG subclass deficiency in cases where no gene deletions have been detected and which are accompanied by recurrent infections due to aberrant immunoregulation. In the present study, we have focused our attention on production by peripheral blood mononuclear cells (PBMCs) of interferon-gamma (IFN-gamma), which is known to induce IgG2 expression. PBMCs from four patients with IgG2 deficiency and their families were studied. Mitogeninduced IFN-gamma production by PBMCs was decreased in all of the patients, although the proliferative responses of PBMCs and the percentages of CD3, CD4, and CD8 T cell subsets were not decreased. IgG2 production by PBMCs was restored upon addition of IFN-gamma and mitogen to the PBMCs of the patients with IgG2 deficiency though it was not restored in the patients with common variable immunodeficiency. We conclude that defects in production of IFN-gamma play an important role in IgG2 deficiency. PMID- 7863260 TI - A polyclonal T cell repertoire of V-alpha and V-beta T cell receptor gene families in intrathyroidal T lymphocytes of Graves' disease patients. AB - We have examined for the presence or absence of T cell receptor V-alpha (VA) and V-beta (VB) gene expression in infiltrating T lymphocytes (ITL) isolated from Graves' thyroid glands in comparison to paired peripheral blood lymphocyte (PBL) samples using a qualitative based polymerase chain reaction (PCR) assay. Sequence specific oligonucleotides for VA and VB T cell receptor gene (TCR) families that had previously been validated in other studies, were used for the PCR analysis, followed by Southern blot hybridization with a labelled, internal C-region primer. A total of seven Graves' disease patients who had been treated with carbimazole were studied. T cell receptor VA and VB gene usage was examined in freshly isolated, unstimulated ITLs from five patients. A widespread usage of VA and VB gene families with 12 to 18 families being used was apparent. Use of oligo dT or C-region priming of the mRNA prior to reverse transcription of the mRNA did not have any significant affect on the results nor did the use of whole Graves' thyroid mRNA as the starting material (n = 2) or perfusion of one gland with saline to remove as much of the contaminating blood from the gland. Our results contrast with those of Davies and colleagues who have previously shown a restricted repertoire of VA gene families in ITLs in comparison to autologous PBLs, and are much more in line with other recent reports indicating a diverse VA repertoire of the infiltrating T cells in Graves' thyroid glands derived from patients treated with anti-thyroid drugs. PMID- 7863261 TI - Monosialoganglioside GM3 induces CD4 internalization in human peripheral blood T lymphocytes. AB - Gangliosides modulate the expression of CD4 molecules on the cell surface of T lymphocytes. We report here that treatment of human peripheral blood lymphocytes with exogenous monosialoganglioside GM3 induces a rapid down-modulation of the CD4 molecules on the plasma membrane of CD4+ T lymphocytes, as assessed by cytofluorimetric analysis and quantitative immunoelectron microscopy. The CD4 down-modulation was ganglioside-dose dependent and was already evident after 5 min of treatment, reaching the maximum after 20 min. The expression of other surface antigens was not affected by GM3 treatment. The immunoelectron microscopic analysis showed that, following GM3 addition, gold labelled CD4 molecules were rapidly redistributed on the cell surface, clustered and internalized via endocytic pits and vesicles. These results indicate that CD4 down-modulation induced by GM3 occurs through an endocytic mechanism. A persistent low level of CD4 expression on the cell surface up to 24 h after GM3 treatment, compared with a stable expression of either CD4 in untreated cells and CD3 in GM3-treated cells, suggests intracellular degradation of the internalized CD4 molecules. PMID- 7863262 TI - Abnormal splenic and thymic IL-4 and TNF-alpha expression in MRL-lpr/lpr mice. AB - The MRL-lpr/lpr and MRL-(++) mice were studied for the expression of cytokines in the spleen, lymph node, thymus, kidney and brain through the reverse transcription-polymerase chain reaction (RT-PCR). The frequencies of IL-4 and TNF alpha expression in the thymus and spleen were significantly higher in MRL lpr/lpr mice than in MRL-(++) mice from the age of 17 to 32 weeks. More importantly, IL-4 transcript was demonstrated in the early rather than in the terminal stage of the lupus disease. At the 20th week, MRL-lpr/lpr mice with active disease exhibited higher concentrations of IL-1 alpha, IL-6 and TNF-alpha in serum than MRL-(++) mice. Interestingly, in MRL-lpr/lpr but not MRL-(++) mice, the IL-6 concentration in cultured supernatants of the thymic cells was significantly higher than that of the splenic or lymph node cells. On the other hand, IL-6 and IL-1 beta were expressed in the brain and kidney of MRL-lpr/lpr mice but not of MRL-(++) mice. Cultured MRL-lpr/lpr mesangial cells could also express IL-6 but to a lesser extent. These results suggest that the abnormal splenic and thymic IL-4 and TNF-alpha expression may predispose the development of autoimmune reactions. The expression of IL-1 beta and IL-6 in the brain and kidney may be implicated in the damage of these two organs in MRL-lpr/lpr mice. PMID- 7863263 TI - Cytokine gene expression during infection of mice lacking CD4 and/or CD8 with Trypanosoma cruzi. AB - The expression of lymphokine genes during infection of virulent (Tulahuen) or mild (CA-I) strains of T. cruzi was studied in mice lacking CD4 and/or CD8 molecules. The increased susceptibility of CD4- and CD4-CD8- mice to infection with CA-I or Tulahuen was parallelled by diminished IFN-gamma mRNA levels. Nitric oxide release and inducible nitric oxide synthase mRNA accumulation by cells from Tulahuen infected CD4- mice was also diminished. CD8- (but not CD4-CD8- mice) showed an increased IL-4 and IL-10 mRNA accumulation upon infection with both strains of T. cruzi. A 'Th2-like' response (higher IL-4 and IL-10 mRNA to IFN gamma mRNA ratio), was also observed when cells from noninfected CD8- mice were stimulated with T cell mitogens. PMID- 7863264 TI - Composition and immunoreactivity of the A60 complex and other cell fractions from Mycobacterium bovis BCG. AB - Surface static cultures of Mycobacterium bovis BCG contained cells embedded in an extracellular matrix, whose mechanical removal yielded free cells that were pressure disrupted and fractionated into cytoplasm and walls. Cell envelopes were either mechanically disrupted or extracted with detergents. Intracellular and extracellular fractions were analysed for proteins, polysaccharides, and antigen 6O (A60), a major complex immunodominant in tuberculosis. A60 was present in extracellular matrix, cytoplasm and walls: it represented a substantial portion of the proteins and polysaccharides of these fractions. While the protein/polysaccharide ratio varied according to the origin of A60 preparations, the electrophoretic patterns of A60 proteins (which accounted for the immunogenicity of the complex) remained unchanged. Western blots pointed to the proteins present within the 29-45 kDa range as the A60 components endowed with the highest immunogenicity level. Since the most heavily stained protein bands in SDS-PAGE patterns were located outside the region best recognized by antisera, a striking discordance was found between concentration and immunogenicity patterns of A60 proteins. The electrophoretic patterns of A60- and non-A60-proteins from cytoplasm were also different. A60 complexes in dot blots and some electrophoresed A60 proteins reacted with monoclonal antibodies directed against lipoarabinomannan (LAM), a highly immunogenic polymer of cell envelope. This contaminating compound was removed from A60 with organic solvents and detergents. SDS-PAGE and Western blot patterns of proteins from delipidated A60 were similar to those of native A60 proteins. PMID- 7863265 TI - Aberrant patterns of immunoglobulin levels in Wiskott-Aldrich syndrome. AB - We have investigated IgM deficiency in Wiskott-Aldrich syndrome patients. From the assessment of T and B cell functions in pokeweed mitogen-induced immunoglobulin (Ig) production, IgM deficiency was chiefly thought to result from B cell dysfunction. The percentages of surface IgM-bearing cells were decreased in peripheral blood mononuclear cells (PBMCs) and the number of IgM-secreting cells was also decreased. Lymphoblast cell lines (LCLs) from the patients have produced IgG and IgA, but never IgM. Moreover the expression of the C mu transcript from the patients' PBMCs and their LCLs were decreased, whereas the C gamma gene was well expressed. No germ-line polymorphism existed between the patients and the controls in the C mu region, and no mutation was detected in the mu s C-terminal and the M exon by nucleotide sequencing. These suggest that the Ig heavy chain (IGHC) isotype switch may be abnormally accelerated in the patients' B cells. While the methylation patterns of the human Ig enhancer gene region were the same between the patient and the control, the methylation patterns of the I gamma 1 region showed less methylation in the patient than in the control, which may cause low IgM expression and high expression levels of other classes located downstream of the IGHC gene. PMID- 7863266 TI - PKC activity and protein phosphorylation in regulation of sIg mediated B cell activation. AB - The inhibitory and stimulatory elements of cellular signalling associated with activation of protein kinase C (PKC) in murine B lymphocytes were investigated by employing two PKC activators with opposing effects on cell proliferation. Being an inhibitor of anti-Ig mediated proliferation, the phorbol ester PDBU induced a more substantial translocation of cytosolic PKC activity than the alkaloid PKC activator indolactam, which enhances anti-Ig mediated B cell proliferation. PDBU and indolactam were equally effective kinase activators, as determined by 32P incorporation of the substrate proteins. Concentrations of indolactam which induced an inhibition of anti-Ig mediated B cell proliferation also induced a precipitous decline in detergent soluble cellular PKC activity, which was comparable with 1 microM PDBU. The induced phosphoprotein patterns were similar, with an exception of the nuclear envelope protein lamin B, which was prominently phosphorylated by PDBU but not by stimulatory concentrations of indolactam. The enhanced phosphorylation of lamin B was associated with cellular growth arrest: inhibitory concentrations of indolactam induced the phosphorylation of lamin B equal to PDBU, whereas an increased phosphorylation of lamin B was never observed upon stimulation with anti-Ig. Together, inhibition of anti-Ig mediated B cell proliferation was related to down-regulation of cytoplasmic PKC and induction of nuclear PKC-dependent phosphorylation. PMID- 7863267 TI - Visceral leishmaniasis in vervet monkeys: immunological responses during asymptomatic infections. AB - Nine vervet monkeys (Cercopithecus aethiops) were infected intradermally with 8 x 10(7) virulent L. donovani promastigotes. Four animals developed clinical visceral leishmaniasis and died over a period of 18 months. The remaining five animals have remained asymptomatic for a period of 3 years now. Attempts to isolate parasites from spleen and liver through biopsies were fruitless. Immunological responses of these subclinically infected animals were examined. Enzyme-linked immunosorbent assay (ELISA) and western blot analyses demonstrated Leishmania specific antibodies in these animals, but the antibody titres were low. When proliferation of peripheral blood monocytes (PBMC) to Concanavalin A (Con A) of these animals was compared with control 'disease free animals' there were no significant differences in response. However, L. donovani antigen (fixed promastigotes) specific proliferation was demonstrated in the five subclinically infected animals. High and varying levels of interferon gamma (IFN-gamma) were secreted in PBMC cultures from the five vervet monkeys when stimulated with either Con A or L. donovani antigens. In control animals, IFN-gamma was only detected when PBMC were stimulated with Con A. Marked delayed-type hypersensitivity (DTH) responses were demonstrated in the five subclinically infected animals 48 h after injection with formalin fixed promastgotes. It was concluded that the visceral Leishmania disease spectrum due to L. donovani observed in humans could be induced in vervet monkeys and that L. donovani asymptomatic/cryptic infected animals have competent humoral and cellular responses to homologous parasites. PMID- 7863268 TI - A dysbalanced immune system in cryptogenic Lennox-Gastaut syndrome. AB - In children with cryptogenic Lennox-Gastaut syndrome we found a functionally impaired humoral immune response to a primary antigen (haemocyanin), despite signs of a triggered immune system consisting of elevated IgG concentrations. This combination of immunological findings, considered to be the expression of a dysbalanced-triggered as well as functionally impaired-immune system, has also been described in an auto-immune disease like systemic lupus erythaematodes in humans, and in genetically epilepsy-prone rats. The interactions between the immune system and the nervous system in Lennox-Gastaut syndrome will be discussed. PMID- 7863269 TI - Rheumatoid arthritis: a medical emergency? AB - Rheumatoid arthritis (RA), previously considered to be a benign controllable disease with a good prognosis in the majority of patients, is now known to be a severe, progressive disease in terms of radiographic damage, severe functional deterioration, progressive work disability and premature mortality. The traditional approach to RA therapy (from less toxic to more toxic drugs) is inadequate and the risk of drug toxicity is generally overestimated while that of severe disease is underestimated. Consequently, aggressive treatment could be considered in an attempt to reverse the inflammation prior to long-term end-organ damage, rather than in response to such damage. As patients with RA may progress to an anticipated 5-year survival similar to that in patients with cardiovascular or neoplastic disease, RA should be viewed as an urgent medical problem--a "medical emergency"--in order to control the long-term consequences of the disease process. PMID- 7863270 TI - Early rheumatoid arthritis: therapeutic strategies. AB - The early stage of rheumatoid arthritis (RA) is a unique and critical phase of disease which is often characterized by profound inflammation, severe symptomatology and a high likelihood of radiological progression. Decisions on treatment strategies need to be taken before irreversible damage and functional deterioration occur. There is evidence that early intervention with disease modifying drugs may reduce functional deterioration and improve long-term outcome. Stable genetic markers and rheumatoid factor are useful in predicting disease severity and thus in identifying those patients who require early aggressive therapy. The acute phase response (APR) is a valuable marker of disease activity and catabolism in RA, and suppression of the APR improves outcome. The use of early aggressive therapy to suppress disease efficiently in patients with a poor prognosis should improve the long-term morbidity and mortality associated with RA. PMID- 7863271 TI - Thyroid disorders in Korean patients with systemic lupus erythematosus. AB - Although autoimmune thyroid diseases have been associated with systemic lupus erythematosus (SLE), the prevalence of thyroid disorder is controversial. To clarify the prevalence of thyroid disorder in Korean patients with SLE, thyroid functions and diseases were evaluated in 63 SLE patients. Of these patients, Hashimoto's thyroiditis (9.5%) as well as euthyroid sick syndrome (14.3%) were more common than Graves' disease (4.8%). The prevalence of antithyroid autoantibodies (antimicrosomal and/or antithyroglobulin autoantibodies) in SLE was 27.0%. High titers of these autoantibodies were mainly detected in Hashimoto's thyroiditis. These results suggested that thyroid diseases are not uncommon in SLE and autoimmune thyroid diseases are possible manifestations in some patients with SLE. Antithyroid autoantibodies may be good predictors for the detection of Hashimoto's thyroiditis developing in SLE. PMID- 7863272 TI - Bone scintigraphy in evaluation of heel pain in Reiter's disease: compared with radiography and clinical examination. AB - Tc-99m MDP bone scans were used to evaluate the heel pain (talalgia) in 38 patients with Reiter's disease, and compared with clinical examination and radiologic findings. In our work, 58% (22/38) patients presented talalgia with a total of 35 lesions. Only two lesions of clinical talalgia were missed by the bone scan. The diagnostic sensitivity was as high as 94% (33/35). However, the diagnostic sensitivity of radiography was only 69% (11/16) when the disease duration was more than one year; furthermore, it declined to 33% (4/12) when the disease duration was less than one year. Based on the bone scans, the correlation between positive scintigraphic findings and clinical talalgia was extremely good. Clinical talalgia occurred in all the 33 lesions demonstrated by bone scan. However, three lesions demonstrated by radiography were not consistent with clinical talalgia and not visualized by radioscintigraphy. Our data show that the radionuclide scan is a more sensitive indicator and has better correlation with clinical talalgia than radiography. We consider that bone scintigraphy is superior to radiography in the evaluation of heel pain in Reiter's disease. PMID- 7863273 TI - Temporomandibular joint involvement in rheumatoid arthritis. Relationship with disease activity. AB - Involvement of temporomandibular joint (TMJ) in rheumatoid arthritis (RA) patients is described, but the incidence varies greatly. In this study our aim was to determine the frequency and character of TMJ involvement in RA patients asymptomatic for this joint, to investigate the relationship with disease activity, and to evaluate the early diagnostic value of imaging techniques. Twenty patients were included in this study, ten were evaluated with computed tomography (CT) and ten with magnetic resonance imaging (MRI). Among the 20 patients 45% had TMJ involvement detected by imaging techniques. The most frequent pathological signs were osteophyte formation, erosion of the mandibular condyle and decreased joint space (40%). Age, duration of disease, number of swollen joints. CRP and RF levels were found to be correlated with TMJ involvement. It is concluded that TMJ involvement may be detected even in asymptomatic patients with RA and there is a positive correlation between the severity of disease and involvement of TMJ. PMID- 7863274 TI - Clinical value of measuring soluble interleukin-2 receptor in polymyalgia rheumatica. AB - Serum levels of soluble interleukin-2 receptor (sIL-2R) were measured in 15 patients with polymyalgia rheumatica (PMR) and followed prospectively for 11.5 months (range 2-22) and also in 22 patients with PMR treated with corticosteroids for a mean period of 47 months. The controls consisted of 21 patients in the same age range as the PMR patients, admitted to the hospital for various diseases, and of 40 healthy younger subjects. The initial sIL-2R values in the patients with newly diagnosed, untreated PMR were significantly higher than the values seen in the same patients after corticosteroid treatment for a median of 6 months and in PMR patients on corticosteroid treatment for more than a year (p < 0.005 and p < 0.05, respectively). However, while being significantly higher than the values in the normal controls, the sIL-2R values in PMR did not differ from the values seen in the hospital controls. Thus, this assay seems to be of little clinical value in the management of patients with PMR. PMID- 7863275 TI - The frequency of transition of chronic low back pain to fibromyalgia. AB - In a retrospective study, the outcome of the chronic low back pain syndrome was investigated in a group of 53 patients. Average time since the diagnosis was established was 18 years. 25% of the patients--all female but one--developed fibromyalgia. The criteria of Yunus and Wolfe, modified by Muller and Lautenschlager, were applied to establish the diagnosis of fibromyalgia. In 60% of the patients chronic low back pain persisted at the time of final examination, while 8 patients were asymptomatic. Predictive parameters for the chance of getting fibromyalgia were sex and postural disorders such as scoliosis. Other radiological findings, for example degenerative changes of the spine, did not coincide with the group of patients who developed fibromyalgia. The predictive value of pain localisation, number of tender points, presence and severity of functional and vegetative symptoms, and the psychosocial situation is uncertain and should be investigated in further long term prospective studies. PMID- 7863276 TI - Muscle fiber characteristics, capillaries and enzymes in patients with fibromyalgia and controls. AB - In 11 female patients with Fibromyalgia Syndrome (FS), biopsies from the m. vastus lateralis were analyzed, in order to reveal any possible changes which might explain muscular weakness and fatigue. Nineteen healthy subjects served as a control group. Light microscopy did not show any gross histopathological findings. Fiber composition and fiber areas did not differ between the two groups, except for a greater coefficient of variation of the area of type II A fibers and of the mean fiber area in the FS group. The number of capillaries per square millimeter and also the fiber area in relation to the capillaries, was lower in the FS patients. Analyses of enzymes showed decreased levels of 3 hydroxy-CoA-dehydrogenase and citrate synthase in the patient group. The reduced oxidative enzyme levels and capillarization indicate reduced physical activity, although this does not associate with muscle fiber hypotrophy. PMID- 7863277 TI - Increased serum angiotensin I-converting enzyme activity in patients with mixed connective tissue disease and pulmonary hypertension. AB - The relationship between serum angiotensin I-converting enzyme (ACE) activity, a possible marker of pulmonary endothelial injury, and the occurrence of pulmonary hypertension (PH) in patients with mixed connective tissue disease (MCTD) was investigated. Before corticsteroid therapy, the mean serum ACE level was 26.4 +/- 14.0 mU/ml in patients with MCTD and PH (n = 6), 16.8 +/- 4.1 mU/ml in patients with MCTD but without PH (n = 18), 16.8 +/- 4.1 mU/ml in patients with undifferentiated connective tissue disease (n = 14), and 16.5 +/- 3.9 mU/ml in controls (n = 18). No significant difference in the enzyme activity was found among the groups. However, 4 patients with MCTD showed increased ACE levels (> 28.3 mU/ml), and all of them had PH. Our results suggest that elevation of serum ACE activity may be related to the occurrence of PH in patients with MCTD. PMID- 7863278 TI - Synovial fluid culture and blood culture in acute arthritis. A multi-case report of 90 patients. AB - The use of blood culture methods for culture of synovial fluid (SF) has been suggested to increase the yield of microbes from SF of patients with septic arthritis. We report on a study of 94 SF cultures of 90 adult patients with acute effusions of the knee joint. Three different culture methods were used: conventional agar plate culture, culture with lysis and centrifugation (Isolator) and broth enrichment (BACTEC 6A and 7A). Blood was cultured simultaneously from 76 patients. In the patients with clinical septic arthritis, the SF cultures were positive by all the methods in 8 patients and negative by all the methods in 19 patients. The contamination rate of the SF cultures was 3/215 in the patients without clinical septic arthritis. We conclude that reliable evidence of septic arthritis is emerged from a SF culture by a single method, and that the choice of culture method is less critical. In addition, we discuss the role of blood cultures in the diagnosis of acute arthritides. PMID- 7863279 TI - The effect of regular intramuscular corticosteroid therapy on bone mineral density in rheumatoid patients. AB - To evaluate the effect of long term regular bolus doses of intramuscular corticosteroid on bone mineral density in rheumatoid patients we undertook a retrospective cross-sectional study of 68 rheumatoid patients. Patients were divided into three groups; those who had received maintenance doses of intramuscular corticosteroid (steroid), those who had been taking regular doses of oral steroid and those who had never received steroid by either route. Bone mineral density (BMD) was measured at the hip and lumbar spine by dual photon X ray absorptiometry (DEXA). Z scores were calculated for each patient at both sites. There is a statistical difference in Z scores at the hip in both steroid treated groups compared with the no steroid group (p < 0.001). Total steroid was less in the IM treated group compared to the oral steroid group. These results suggest that maintenance therapy with IM steroids produces significant losses of bone mineral density at the hip in rheumatoid patients and that this effect appears to be independent of the total dose. PMID- 7863280 TI - Effect of intraarticular osmic acid on synovial membrane volume and inflammation, determined by magnetic resonance imaging. AB - The changes in MR-determined synovial membrane volume, early synovial enhancement, and cartilage and bone erosions after osmic acid knee synovectomy were studied. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) of 18 knees with persistent arthritis was performed before and 1 month after treatment. The synovial membrane volume was significantly reduced (median -52%) in all 9 patients brought into clinical remission (p < 0.01), while no significant change was found in patients with clinical relapse. The early synovial enhancement was not significantly changed. MRI revealed progressive erosive changes in 2 patients. The time of relapse was correlated to a MR-erosion score, but not to early synovial enhancement or volumes of synovium or effusion (Spearman tests). MRI-determined synovial membrane volumes and early synovial enhancement may be objective quantitative markers of inflammation. MR-scores of cartilage and bone erosions are sensitive to progressive changes occurring within a month. PMID- 7863281 TI - Arthritis after hepatitis B vaccination. Report of three cases. AB - Side effects of hepatitis vaccination are rare. Only a few cases of arthritis after hepatitis vaccination have been published. We report on three cases of vaccination-induced arthritis with different resulting disease. Two cases show the pattern of reactive arthritis. None of them was associated with HLA-B27. In the third case onset of rheumatoid arthritis was triggered by hepatitis vaccination. These three cases show that arthritis after hepatitis B vaccination probably is more common than reported so far, especially in a genetically predisposed subject (two of our patients expressed HLA-DR4). PMID- 7863282 TI - Psoriatic onycho-periostitis. Report of three cases. AB - Authors report three cases of psoriatic onycho-periostitis (great toe in two cases, thumb in one case). In a recent study, they demonstrated that osteoperiostitis of the distal phalanx of the great toe was significantly more frequent in patients with psoriatic arthritis than in other groups (cutaneous psoriasis, rheumatoid arthritis, spondylarthropathy, connective tissue diseases, and control subjects), suggesting that the existence of osteoperiostitis of the distal phalanx of the great toe is valuable for the diagnosis of psoriatic arthropathy. PMID- 7863283 TI - Lacrimo-auricolo-dento-digital syndrome mimicking primary juvenile Sjogren's syndrome. AB - We describe a 24 year old female patient affected with symptoms of severe xerostomia and keratoconjunctivitis sicca since her childhood. She also had several malformations involving face and digits as well as cup shaped ears, enamel dysplasia and absence of lacrimal puncta. Hence, the diagnosis of Lacrimo Auricolo-Dento-Digital (LADD) syndrome was made. The main differences between this rare, inherited disease and primary juvenile Sjogren's syndrome are pointed out. PMID- 7863284 TI - Angioimmunoblastic lymphadenopathy with disproteinemia arising in a patient with rheumatoid arthritis. AB - Angioimmunoblastic lymphadenopathy with disproteinemia (AILD) is a systemic lymphoproliferative disorder characterized by constitutional symptoms such as generalized lymphadenopathy, hepatosplenomegaly and skin rash. In this article, we report on a patient with seronegative Rheumatoid Arthritis of 18 years duration who recently developed AILD. PMID- 7863285 TI - Resection+carotid flap plasty. A new surgical technique for newborn children with coarctation of the aorta and critical hypoplasia of the aortic arch. AB - Coarctation of the aorta with critical hypoplasia of the aortic arch is a ductus dependent malformation-complex often combined with severe intracardiac malformations with a common denominator: there is a predominance of the pulmonary circulation and a flow restriction through the ascending aorta. Coarctation of the aorta with critical hypoplasia of the aortic arch may be looked upon as a malformation bordering on hypoplastic left heart syndrome. The degree of aortic arch hypoplasia seems to mirror the severity of the intracardiac malformation. The first objective in reconstructing these hearts is to create an unobstructed flow through the aortic arch. Resection of the coarcted segment combined with carotid flap plasty is a surgical alternative which fulfils this objective. We have used the technique in premature-born and severely ill neonates where one step total correction was considered contraindicated. Thirteen neonates were operated upon, there were no cerebral consequences referable to the carotid artery ligation and no recoarctations. PMID- 7863286 TI - Factors influencing survival in total anomalous pulmonary venous drainage. AB - Surgical repair of total anomalous pulmonary venous drainage was performed on 20 patients in 1977-1986. In univariate and multivariate and survival-curve analyses of clinical, anatomic and haemodynamic features, elevated diastolic pulmonary artery pressure was the only parameter prognostic of total mortality. The early mortality rate was 25% and the 5-year survival was 65 +/- 10.6%. Anastomotic stenosis occurred in four patients, three of whom underwent reoperation; one patient was twice operated on for such stenosis. PMID- 7863287 TI - Acute type A aortic dissection--diagnostic aspects and surgical experience. AB - Acute type A aortic dissection was surgically treated in 33 patients aged 20-65 years, all critically ill on admission to hospital. Transthoracic echocardiography revealed pericardiac tamponade in eight cases of extreme emergency, indicating surgery without need of additional imaging. Transesophageal echocardiography provided a definitive diagnosis in 16 cases, with excellent reliability and no false positive findings. Composite graft replacement with button technique was used in 24 patients and other methods of repair in nine. The perioperative mortality was 12% (4/33) and the late mortality 7% (2/29). The actuarial 5-year survival rate was 73%. No aortic root reoperation was required during follow-up for a mean of 4 years. Transesophageal echocardiography proved to be an accurate tool for speedy diagnosis of acute type A aortic dissection and open composite graft replacement with button technique highly satisfactory treatment, avoiding late aortic root problems. PMID- 7863288 TI - Myocardial release of troponin T after coronary bypass surgery. AB - The temporal changes in cardiac S-troponin T, S-creatine kinase-MB(S-CK-MB)mass and S-myoglobin were studied for 5 days after coronary bypass grafting in 70 patients. Perioperative infarction occurred in ten patients (2 Q wave, 8 non-Q wave). All three markers showed significant increase even in patients without signs of perioperative infarction. Within 8-12 hours their levels rose significantly (p < 0.001) more in the infarction than in the non-infarction cases. Troponin T and CK-MBmass both showed early (< 8-12 h) peaks in patients with perioperative infarction. CK-MBmass returned to near normal levels within 48 72 hours, whereas troponin T remained markedly increased throughout the observation. Myoglobin concentrations varied widely among the infarction cases. In the non-infarction group, troponin T and CK-MBmass (but not myoglobin) were related to the aortic cross-clamp time. Troponin T (but not CK-MBmass) remained elevated throughout the study period in patients with longer cross-clamp times. These findings may indicate continuous release from damaged myocardium in cases of perioperative infarction. Troponin T and CK-MBmass can serve as markers of perioperative infarction and troponin T may also be useful as a marker in studies on myocardial protection. PMID- 7863289 TI - Reperfusion ventricular fibrillation and electric countershocks during coronary artery bypass operations--association with postoperative CK-MB release. AB - Reperfusion ventricular fibrillation during coronary artery bypass surgery is common and electric shocks are often needed to terminate it. Both the fibrillation and the reversing electric shocks are potentially detrimental to the myocardium. In 61 aortocoronary bypass patients with uncomplicated clinical course (no difficulties in weaning from bypass, no ECG changes and no inotropic medication), serial creatine kinase-MB values were recorded. Evaluated explanatory variables were patient age, ejection fraction, aortic occlusion time, perfusion time, number of peripheral anastomoses and of anastomoses to marginal branches, myocardial fibrillation time before aortic cross-clamping, after cross clamping prior to cardiac arrest and after declamping, and number of defibrillations. The results indicated that reperfusion fibrillation times up to 10 minutes are not harmful, provided that left ventricular decompression is carried out. Too early and thus numerous defibrillations raise creatine kinase-MB levels and probably also damage the myocardium, and therefore should be avoided. PMID- 7863290 TI - Surgical management of substernal goiter. AB - Seventeen cases of large substernal goiter are reviewed. The commonest clinical features were frequent upper respiratory tract infections, dyspnea and a cervical mass. Five of the patients had previous thyroidectomy. The substernal goiter was located in the right chest in 11 cases, the left chest in five and bilaterally in one case. On computed tomograms it was pretracheal or prevascular in ten cases and retrovascular in seven. Tracheal deviation was present in 15 cases, causing tracheal compression or stenosis in 14. Thyroidectomy was performed on all 17 patients (8 subtotal, 9 total) through a low transverse collar incision. The recommended technique for substernal goiter extending from the neck to a level below the subcarinal region includes concomitant finger dissection and upward traction of the cervical thyroid through the subcapsular plane, with obliteration of the postresection substernal dead space by sutures. Follow-up radiography showed that all the deviated tracheas had resumed near normal position 2-3 months postoperatively and the average diameter of the compressed tracheas had increased significantly. PMID- 7863291 TI - Management of intrathoracic goitre. AB - A retrospective review is presented of 20 cases with resection of intrathoracic goitre between 1975 and 1993. The mean age of the 11 men and nine women was 53 years. The intrathoracic goitre was primary in seven cases and secondary in 13. The presenting clinical features and the pathology, surgical risks and optimal approaches are discussed. Primary intrathoracic goitre should be approached via a thoracotomy, because of the independent vascular supply. As secondary intrathoracic goitres are supplied by vascular pedicles arising from the inferior thyroid artery, a cervical collar incision is preferable. In the event of significant mediastinal bleeding, which is difficult to control from a cervical incision, a T-shaped incision for partial or full sternotomy can be performed, or even thoracotomy. PMID- 7863292 TI - Near-total esophageal exclusion in the treatment of late-diagnosed esophageal perforation. AB - Two cases of late-diagnosed esophageal perforation were successfully treated with near-total esophageal exclusion, using cervical T-tube esophagostomy with circumferential suture fixation of the lower arm of the T-tube. Esophageal stricture developed at the site of catgut or dexon tie. This complication can be managed with esophageal dilation. Drainage-tube gastrostomy proved to be unnecessary. PMID- 7863293 TI - Thoracoscopic assisted paraoesophageal hernia repair. AB - A video assisted thoracic surgical repair of a paraoesophageal hernia is described. The advantage of the procedure was the combination of the diagnostic and therapeutic facility characteristic of a transthoracic approach without exposing the patient to the morbidity of formal thoracotomy. PMID- 7863294 TI - Cancer occurrence among workers exposed to acrylonitrile. AB - A MEDLINE search identified 12 published epidemiologic studies that have reported incidence or mortality experience among workers exposed to acrylonitrile. Many of the studies contain scanty descriptions of subject ascertainment, and most do not have good information on exposure assessment. Many also may have suffered from incomplete follow-up, as evinced by an overall deficit in the number of deaths observed, compared with the number expected from general population mortality rates. Such problems are not unique to studies on acrylonitrile, and to some extent they reflect the difficulties of conducting retrospective cohort studies. Despite these drawbacks, a simplified meta-analysis of the mortality experience reported for these cohorts revealed little evidence for carcinogenicity. Approximately the same number of cancer deaths was observed as was expected according to general population mortality rates (standardized mortality ratio 1.03, 90% confidence interval 0.92-1.15). The combined information from these studies is insufficient to support confidence about a lack of carcinogenicity at all sites. Nevertheless, despite the flaws in some of the individual studies, the summarized findings offer reassurance that workers exposed to acrylonitrile face no striking increases in mortality for all cancers or for respiratory cancer. PMID- 7863295 TI - Bladder cancer and occupational exposures. AB - OBJECTIVES: A hospital-based case-referent study was carried out in Lyon with the purpose of generating hypotheses about the role of occupational exposures to 320 compounds in bladder carcinogenesis. METHODS: Job histories were obtained by questionnaire for 116 cases and 232 reference patients with diseases other than cancer (one referent from the same hospital ward and one from another ward of the same hospital per case); the referents were matched for gender, hospital, age, and nationality. Systematic coding of exposures, with a blind analysis of job histories, was carried out by a team of experts in chemistry and occupational health. RESULTS: Significantly elevated odds ratios were observed for exposure to pyrolysis and combustion products [odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.0-4.0] when the general referents were used and for cutting fluids (OR 2.6, 95% CI 1.2-5.4) when tobacco consumption was adjusted for. The latter was highest among the category consisting of blue-collar and unskilled workers, supervisors, and agricultural workers (OR 4.6 95% CI 2.0-10.6), while the odds ratio for the other category was 0.8 (95% CI 0.3-2.7). An elevated odds ratio for exposure to inks was observed for the women (OR 14.0, 95% CI 1.8-106.5) on the basis of 14 exposed cases, but confounding factors could have been responsible for this result. Odds ratios for several other exposures (rubber: OR 5.7, nitrates: OR 8.2, coke dust: OR 3.5, meat additives: OR 3.8) were also elevated, but not significantly so when based on a small number of exposed cases. CONCLUSION: The observations of this investigation should be tested in future studies, in particular since exposures to agents such as cutting fluids or pyrolysis products are ubiquitous in industrial settings and may present an important public health hazard. PMID- 7863296 TI - Mortality of filling station attendants. AB - OBJECTIVES: Gasoline contains established human carcinogens, such as benzene. The health impact of exposure to this fuel, however, has not been fully elucidated. We report on the mortality of a cohort of 2665 filling station managers from the Latium region (Italy). METHODS: This is the first workplace-based cohort of gas station attendants. However, only self-employed individuals were available for study (about 50% of the whole work force). The follow-up period extended from 1981 through 1992. The mortality experience of the cohort was compared with that of the regional population. RESULTS: The overall analysis for standardized mortality ratios (SMR) showed a significantly decreased mortality from all causes, mainly due to a deficit of cardiovascular diseases and malignant neoplasms. Nonsignificantly increased risks for esophageal cancer [SMR 241, 90% confidence interval (90% CI) 82-551], brain cancer (SMR 195, 90% CI 77-401) and non-Hodgkin's lymphoma (SMR 173, 90% CI 47-448) were found for the men; mortality due to lung cancer and leukemia was lower than expected, and no kidney cancer death was recorded. Among the attendants of small stations (characterized by a small number of employees and high sales of gasoline per full-time employee), the SMR values for esophageal cancer (for men SMR 351, 90% CI 120-803) and brain cancer (for men and women SMR 266, 90% CI 105-559) showed increased values. CONCLUSIONS: Filling station attendants are exposed to gasoline vapors and seem at risk of cancer of various sites. Due to the power limitations of this study, however, a precise estimate of the risk for many causes of death was not achievable. Further cohort studies of greater size are warranted. PMID- 7863297 TI - Incidence of cancer among workers in Norwegian hydroelectric power companies. AB - OBJECTIVES: The goal of this study was to examine whether exposure to electric or magnetic fields is related to cancer. METHODS: The study cohort consisted of 5088 men who had worked for at least one year between 1920 and 1991 for any of eight participating companies which produce and distribute hydroelectric power in Norway. The occupational exposure of these workers included extremely low frequency electromagnetic fields. Incident cancer cases identified from the Cancer Registry of Norway were analyzed on the basis of the standardized incidence ratio with the Norwegian male population as reference. RESULTS: The incidence of cancer was close to unity for the cohort. The standardized incidence ratio for lymphoma was below unity, whereas those for leukemia and brain tumors were similar to those expected. Calculated cumulative exposure to electric or magnetic fields was not associated with the incidence of leukemia or brain tumors, but an excess of malignant melanoma was shown for the highest category of magnetic field exposure. An analysis of combined possible exposure to oils containing polychlorinated biphenyls and exposure to magnetic fields or possible exposure to electric sparks gave standardized incidence ratios of 265 and 280, respectively, for the higher exposure category. CONCLUSIONS: These results do not support the assumption of a possible association between exposure to electromagnetic fields and leukemia and brain tumors. The possible association between exposure to polychlorinated biphenyls or magnetic fields and risk of malignant melanoma should be further evaluated in future studies. PMID- 7863298 TI - Gender ratio of offspring and exposure to shortwave radiation among female physiotherapists. AB - OBJECTIVES: The goal of this study was to investigate whether the deficit of male births found among the offspring of Danish physiotherapists exposed to shortwave radiation during the first month of their pregnancy could be confirmed among the offspring of physiotherapists from Switzerland. METHODS: A self-administrated questionnaire was mailed (two mailings) to all of the 2846 female members of the Swiss Federation of Physiotherapists. It included questions on the gender and birth-weight of all children of the physiotherapists, as well as on the use of shortwave or microwave equipment during the first month of each pregnancy. The response rate was 79.5%, and the analysis was based on 1781 pregnancies. RESULTS: The gender ratio (the number of males per number of females x 100) was 107 with a 95% confidence interval (95% CI) of 89-127 for the 508 pregnancies exposed to shortwave radiation and 101 (95% CI 90-113) for the 1273 unexposed pregnancies. There was no trend in the gender ratio with increasing intensity or duration of exposure. The prevalence of low birthweight (< or = 2500 g) was not related to exposure to shortwave radiation for either the boys or the girls. CONCLUSIONS: No atypical gender ratio was found for the children of female physiotherapists from Switzerland who had been exposed to shortwave radiation at the beginning of pregnancy. The findings of the Danish study could not be confirmed. PMID- 7863299 TI - Association between ambulatory blood pressure and alternative formulations of job strain. AB - OBJECTIVES: The goal of the study was to determine whether alternative formulations of Karasek & Theorell's job-strain construct are associated with ambulatory blood pressure and the risk of hypertension. METHODS: Full-time male employees (N = 262) in eight worksites completed a casual blood pressure screening, medical examinations, and questionnaires and wore an ambulatory blood pressure monitor for 24 h on a workday. Cases of hypertension were ascertained from casual blood pressure readings for a case-referent analysis. A cross sectional analysis was also conducted, ambulatory (continuous) blood pressure measurements being used as the outcome. RESULTS: All formulations of job strain exhibited significant associations with systolic blood pressure at work and home, but not with diastolic blood pressure. Employees experiencing job strain had a systolic blood pressure that was 6.7 mm Hg (approximately 0.89 kPa) higher and a diastolic blood pressure that was 2.7 mm Hg (approximately 0.36 kPa) higher at work than other employees, and the odds of hypertension were increased [odds ratio (OR) 2.9, 95% confidence interval (95% CI) 1.3-6.6]. Using national means for decision latitude and demands to define job strain increased the systolic and diastolic blood pressure associations to 11.5 mm Hg (approximately 1.53 kPa) and 4.1 mm Hg (approximately 0.54 kPa), respectively. Adding organizational influence to the task-level decision latitude variable produced a stronger association for hypertension with job strain (OR 3.7, 95% CI 1.6-8.5). Adding social support to the job-strain model also slightly increased the hypertension risk. CONCLUSIONS: The impact of job strain, at least on systolic blood pressure, is consistent and robust across alternative formulations, more restrictive cut points tending to produce stronger effects. PMID- 7863300 TI - Role of migrant factors in work-related fatalities in Australia. AB - OBJECTIVES: The importance of workers' language and migration characteristics to safety in the work environment has been debated but remains unclear. This study examined the role of these factors in the occurrence of work-related fatalities in Australia. METHODS: The study was based on an investigation of all work related fatalities occurring in Australia during 1982-1984. Denominators for each year were obtained according to gender and country-of-birth census data from the 1981 and 1986 national censuses, interpolated and adjusted according to annual labor force survey estimates for the period 1981 to 1986 to indicate the true movement of the employed civilian labor force over the study period. RESULTS: Of 1211 decedents identified with known country of birth, 333 were born outside of Australia. The overall fatality incidence per 100,000 person-years in the employed civilian labor force was 7.12 [95% confidence interval (95% CI) 6.36 7.88], which is similar to that of Australian-born persons, 6.56 (95% CI 6.12 6.99). However, fatality incidences in rural and mining occupations were significantly increased among overseas-born persons when they were compared with Australian-born persons. Mortality ratios standardized separately for occupation and age showed significantly elevated mortality for duration of residence of less than five years, particularly for persons of non-English speaking background. These values converged to the Australian rate with increasing duration of residence. CONCLUSION: This study suggests that factors related to country of birth (eg, language) and duration of residence of overseas-born workers are important determinants of safety at work in Australia. PMID- 7863301 TI - Comparison of information sources for case-referent data. AB - OBJECTIVES: Exposure assessment and the ascertainment of cases are topics of main concern in epidemiologic research. To investigate validity aspects of this kind practically, a comparative evaluation was performed of information sources for case-referent data. METHODS: Cases of Hodgkin's disease and non-Hodgkin's lymphoma diagnosed in 1975-1984 were collected from the Regional Cancer Register in Linkoping. The study population was restricted to men 20-80 years of age at diagnosis. Living cases included in a previous case-referent study and the complementary cases from the register were compared with regard to the exposures indicated by job title and industrial branch, as given in the National Population Census in 1975. Furthermore, questionnaire-based exposure information from the case-referent study was compared with exposures derived from census information. RESULTS: Only 21% of all of the cases in the study base had been included in the questionnaire-based case-referent study. No major differences in the distribution of exposure were found for the two case series, except that fewer subjects were economically inactive in the previous case-referent study. No clear relations appeared between survival and particular exposures. Risk estimates derived from the present cancer register study were compared with corresponding estimates from the previous case-referent study. With restriction to only economically active cases, the risk estimates approached those of the case-referent study. CONCLUSIONS: This comparison showed that incomplete ascertainment of cases in a case-referent study was not an important source of bias, at least not in relation to what could be achieved by more complete case ascertainment through register linkage. PMID- 7863302 TI - CD8 T-cell clones producing interleukin-5 and interferon-gamma in bronchial mucosa of patients with asthma induced by toluene diisocyanate. AB - OBJECTIVES: The aims of the present study were to determine whether specific in vivo stimulation of asthmatics sensitized with toluene diisocyanate (TDI) induces the activation of T lymphocytes in bronchial mucosa and to characterize their phenotype and cytokine secretion profile. METHODS: Bronchial biopsies from two subjects with occupational asthma due to TDI were obtained 48 h after an asthmatic reaction induced by an inhalation challenge with TDI and after three months of no exposure to TDI, at the time when the subjects had recovered from their asthma. The fragments of bronchial mucosa were cultured in the presence of interleukin-2 so that the in vivo activated T cells present in the tissue would expand, and T blasts were then cloned under limiting dilution conditions. RESULTS: From the two 48-h specimens, 65 and 63 T-cell clones were obtained. Most of the clones exhibited the CD8 phenotype (82 and 83%). All of the CD8 clones produced interferon-gamma and 44% produced interleukin-5, but only 6% secreted interleukin-4 as well. Three months after the cessation of exposure, growing T cells could not be recovered from bronchial biopsies cultured in interleukin-2. CONCLUSIONS: The results suggest that, in sensitized subjects, exposure to TDI induces the activation of a subset of CD8 lymphocytes producing interferon-gamma and interleukin-5. PMID- 7863303 TI - Computerization of the health record, nursing informatics as a specialty. PMID- 7863304 TI - AASCIN strategic plan--1993-1998. AB - A long-standing commitment to planned growth and development are essential for the AASCIN to be effective in influencing the direction of spinal cord injury (SCI) nursing. Recognizing these needs, a long-range planning initiative was supported by the Board of Directors in March, 1990. A task force was charged with the responsibility for outlining the future of the AASCIN through the development of a five-year strategic plan. The long-range planning initiative was divided into two segments. First, a Delphi Study was developed to obtain membership input into AASCIN's priorities. Once this data was collected, the Strategic Planning Task Force synthesized the results of the study and developed a five-year AASCIN strategic plan. The purpose of this article is to describe the process and content of the proposed AASCIN strategic plan. The report begins with a brief description of the Delphi Survey, which forms the foundation for the strategic plan. Since the strategic plan needs to be congruent with the organization's mission statement and goals, the organizational plan of AASCIN is presented. Lastly, a brief summary of how the organization proposes to use this strategic planning document is provided. PMID- 7863305 TI - The neurophysiological basis of learning: attention and memory implications for SCI nurses. AB - Understanding the neurophysiological basis of learning enables nurses working with individuals with spinal cord injury to astutely assess potential for learning. This is particularly relevant when head injury or drug effects influence neurological systems relevant to learning. The neuroanatomical and neurophysiological bases of learning are related to attention, memory, concept formation/abstraction, reasoning, and executive systems. Attention and memory are discussed as they relate to learning in this article. This information is incorporated into an expanded assessment (Ciminaro, Calhoun, & Adams, 1977; Gazzaniga 1979; Lezak, 1983: Mesulam, 1985). More in-depth nursing assessment related to cognitive systems necessary for learning enables nurses to identify intact and impaired cognitive systems and to quantify deficits. Astute assessment is fundamental to planning effective teaching and learning strategies for spinal cord injured persons especially when learning deficits exist, e.g., in head injured persons who have sustained a spinal cord injury. Implications for client and family education derive from an understanding of the normal neurophysiological basis of learning and normal and abnormal assessment findings. Learning is dependent on several cognitive systems--attention systems, memory systems, concept formation/abstraction and reasoning systems, and the "executive" system. Attention and memory systems are discussed in this article, the remainder will be discussed in the next issue. The neuroanatomy and neurophysiology, clinical findings associated with normal and abnormal function, and nursing implications for the nurse working with individuals with spinal cord injury will be explored. PMID- 7863306 TI - Standards and guidelines. PMID- 7863307 TI - Clinical evaluation of Dermagran spray and ointment in the treatment of pressure ulcers in spinal cord injury. PMID- 7863308 TI - Integrating ACHPR's pressure ulcer guidelines with AASCIN's research agenda. PMID- 7863309 TI - Impacting health care: study of a reusable urinary drainage system. AB - This study of a reusable urinary leg bag system was undertaken to ascertain possible increased incidence of urinary tract infection attributable to reusing urinary leg bags. The fourteen patients involved had diagnoses of "neurogenic bladder," and required long-term drainage. Ten were on Foley catheter drainage and four were on external drainage. Before the reusable bags were placed into use, urine cultures were collected to establish baseline information about prevalent urinary organisms for each subject. During the study period, random urine specimens for culture/sensitivity were collected. Analysis of the findings of this study demonstrates no increase in incidence of urinary tract infection attributable to use of reuseable leg bags for urinary drainage. PMID- 7863310 TI - Multicenter research. PMID- 7863312 TI - SCI patients with recurrent pressure ulcers. PMID- 7863311 TI - The neurophysiological basis of learning, Part 2: Concept formation/abstraction, reasoning and executive functions--implications for SCI nurses. AB - Understanding the neurophysiological basis of learning enables nurses working with spinal cord injured persons to astutely assess potential for learning. This is particularly relevant when head injury or drug effects are influencing neurological systems relevant to learning. The neuroanatomical and neurophysiological bases of learning are related to attention, memory, concept formation/abstraction, reasoning, and executive systems. Concept formation/abstraction, reasoning and executive systems are discussed as they relate to learning in this article. This information is incorporated into expanded assessment. More in-depth nursing assessment related to cognitive systems necessary for learning enables nurses to identify intact and deficit cognitive systems and quantify deficits. Astute assessment is fundamental to planning effective teaching and learning strategies for spinal cord injured persons especially when learning deficits exist, e.g., in head injured persons who have sustained a spinal cord injury. Implications for client and family education derive from an understanding of the normal neurophysiological basis of learning and normal and abnormal assessment findings. PMID- 7863313 TI - Standards of spinal cord injury nursing practice. The American Association of Spinal Cord Injury Nurses. PMID- 7863314 TI - Strategies for the management and control of antibiotic resistant organisms on a spinal cord injury unit. AB - Individuals with a spinal cord injury (SCI) are at an increased risk of infection and colonization. Frequent lengthy hospitalizations, invasive procedures, and skin breakdown contribute to this risk. Intermittent antibiotic use influences the emergence of antibiotic resistance in these organisms. As a result, there is risk of transmission of these antibiotic resistant organisms (ARO). This article describes the application of a continuous quality improvement model to evaluate ARO management strategies in a SCI unit. A conservative, labor intensive, crisis management approach to the control of ARO was replaced with a more cost effective prospective plan. The new strategies were aimed at control rather than eradication and included collaborative, multidisciplinary planning and improved resource utilization. Efforts have been successful and have resulted in the control of ARO. PMID- 7863315 TI - SCI care: the guiding light. PMID- 7863316 TI - President's message: the nurse specializing in SCI. PMID- 7863317 TI - Transurethral placement of external sphincter wire mesh stent for neurogenic bladder. AB - Literature reports experience using a transurethral prosthetic stent for the treatment of neurogenic bladder in males with spinal cord injury who also have detrusor-external sphincter dyssynergia (DESD). The Urolume prosthesis, a cylindrical wire mesh stent, was inserted in the membranous urethra of 25 spinal cord injured males with DESD and elevated voiding pressure. Patient education regarding care of external condom urine collecting devices was an important preoperative requirement ensuring long-term success. One-year post-stent placement subjects showed a statistically significant decrease in voiding pressure and residual urine volume. Bladder capacity remained constant. All subjects were able to achieve spontaneous reflexive voiding without constant dribbling. There were no complications of bladder stone formation, tissue overgrowth within the stent, untoward effects on renal or erectile function, or pain. Patients reported decreased autonomic dysreflexia symptoms and significant psychosocial benefits such as decreased incontinence and freedom from indwelling catheters. Patient satisfaction, ease of placement, and minimal associated morbidity make sphincter stent placement an effective alternative to external sphincterotomy. PMID- 7863318 TI - Protocol for weaning the SCI patient. AB - Ventilator weaning may be defined as the discontinuation of mechanical ventilation in patients with acute respiratory failure, based upon predetermined objective criteria and accompanied by appropriate physiological and psychological monitoring (Luce, Tyler & Pierson, 1984). This paper presents a protocol for weaning the person with an acute spinal cord injury (SCI) from the ventilator. Patients are divided into uncomplicated and complicated categories. Specific guidelines identify the physiological parameters used as our criteria for weaning the person with SCI. Specific recommendations for weaning are based on 15 years of experience at a regional SCI Center which admits over 100 persons with SCI per year. Over the past 20 months alone, we have had a 94% success rate in utilizing this protocol for the ventilation weaning of uncomplicated and complicated individuals with SCI. We believe it provides consistent guidelines for the practitioner in successfully weaning the person with SCI from the ventilator. PMID- 7863319 TI - Product evaluation column. PMID- 7863321 TI - What are some strategies for managing the "difficult patient" on a spinal cord injury unit? PMID- 7863320 TI - Why multicenter research? PMID- 7863323 TI - Medication errors: decreasing their incidence. PMID- 7863322 TI - Caring and the health professions. AB - This study analyzes patient descriptions of what constitutes caring in the physician and nurse. We propose that health care students can be taught caring behavior through the use of patient narratives. PMID- 7863324 TI - The state of South Dakota's child: 1994. AB - This annual report reviews natality and infant mortality data and also reviews teenage pregnancy in South Dakota. Data for 1993 again document a declining rate of birth for South Dakota with a 3% decline in the number of births since 1990 and an 18% decline since 1980. An identical number of infants (102) died in 1993 as 1992 with neonatal mortality slightly declining and post neonatal mortality slightly increasing for the state. Rates of perinatal causes of infant death are lower in South Dakota than they are nation-wide, but are higher for congenital anomalies, sudden infant death, pneumonia/influenza, and injuries/homicide. The 1993 birth rate per 1,000 teenagers 15-19 years of age in South Dakota was 44.5 compared to the 1992 rate of 60.7 for the United States. In South Dakota the rate of teen births for American Indian mothers is over four times higher than that for whites. The American Indian rate is also higher than that observed for Indians nation-wide. Alternately, the South Dakota white rate of birth to this age group is lower than the national rate. For all babies born to teenage mothers, 69% of the fathers are beyond their teen years. The need to examine teen pregnancy as a societal, and not just an adolescent problem, is emphasized. PMID- 7863325 TI - Numbers and ratios of visual pigment genes for normal red-green color vision. AB - Red-green color vision is based on middle-wavelength- and long-wavelength sensitive visual pigments encoded by an array of genes on the X chromosome. The numbers and ratios of genes in this cluster were reexamined in men with normal color vision by means of newly refined methods. These methods revealed that many men had more pigment genes on the X chromosome than had previously been suggested and that many had more than one long-wave pigment gene. These discoveries challenge accepted ideas that are the foundation for theories of normal and anomalous color vision. PMID- 7863326 TI - Peptide specificity in the recognition of MHC class I by natural killer cell clones. AB - Recognition by natural killer (NK) cells of major histocompatibility complex (MHC) class I molecules on target cells inhibits NK-mediated lysis. Here, inhibition of NK clones by HLA-B*2705 molecules mutated at single amino acids in the peptide binding site varied among HLA-B*2705-specific NK clones. In addition, a subset of such NK clones was inhibited by only one of several self peptides loaded onto HLA-B*2705 molecules expressed in peptide transporter-deficient cells, showing that recognition was peptide-specific. These data demonstrate that specific self peptides, complexed with MHC class I, provide protection from NK mediated lysis. PMID- 7863327 TI - Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD. AB - Skeletal muscle differentiation entails the coordination of muscle-specific gene expression and terminal withdrawal from the cell cycle. This cell cycle arrest in the G0 phase requires the retinoblastoma tumor suppressor protein (Rb). The function of Rb is negatively regulated by cyclin-dependent kinases (Cdks), which are controlled by Cdk inhibitors. Expression of MyoD, a skeletal muscle-specific transcriptional regulator, activated the expression of the Cdk inhibitor p21 during differentiation of murine myocytes and in nonmyogenic cells. MyoD-mediated induction of p21 did not require the tumor suppressor protein p53 and correlated with cell cycle withdrawal. Thus, MyoD may induce terminal cell cycle arrest during skeletal muscle differentiation by increasing the expression of p21. PMID- 7863328 TI - Inhibition of myogenic differentiation in proliferating myoblasts by cyclin D1 dependent kinase. AB - Although the myogenic regulator MyoD is expressed in proliferating myoblasts, differentiation of these cells is limited to the G0 phase of the cell cycle. Forced expression of cyclin D1, but not cyclins A, B, or E, inhibited the ability of MyoD to transactivate muscle-specific genes and correlated with phosphorylation of MyoD. Transfection of myoblasts with cyclin-dependent kinase (Cdk) inhibitors p21 and p16 augmented muscle-specific gene expression in cells maintained in high concentrations of serum, suggesting that an active cyclin-Cdk complex suppresses MyoD function in proliferating cells. PMID- 7863329 TI - p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells. AB - Terminal differentiation is coupled to withdrawal from the cell cycle. The cyclin dependent kinase inhibitor (CKI) p21Cip1 is transcriptionally regulated by p53 and can induce growth arrest. CKIs are therefore potential mediators of developmental control of cell proliferation. The expression pattern of mouse p21 correlated with terminal differentiation of multiple cell lineages including skeletal muscle, cartilage, skin, and nasal epithelium in a p53-independent manner. Although the muscle-specific transcription factor MyoD is sufficient to activate p21 expression in 10T1/2 cells, p21 was expressed in myogenic cells of mice lacking the genes encoding MyoD and myogenin, demonstrating that p21 expression does not require these transcription factors. The p21 protein may function during development as an inducible growth inhibitor that contributes to cell cycle exit and differentiation. PMID- 7863330 TI - Temporal information transformed into a spatial code by a neural network with realistic properties. AB - Neurons exhibit a wide range of properties in addition to postsynaptic potential (PSP) summation and spike generation. Although other neuronal properties such as paired-pulse facilitation (PPF) and slow PSPs are well characterized, their role in information processing remains unclear. It is possible that these properties contribute to temporal processing in the range of hundreds of milliseconds, a range relevant to most complex sensory processing. A continuous-time neural network model based on integrate-and-fire elements that incorporate PPF and slow inhibitory postsynaptic potentials (IPSPs) was developed here. The time constants of the PPF and IPSPs were estimated from empirical data and were identical and constant for all elements in the circuit. When these elements were incorporated into a circuit inspired by neocortical connectivity, the network was able to discriminate different temporal patterns. Generalization emerged spontaneously. These results demonstrate that known time-dependent neuronal properties enable a network to transform temporal information into a spatial code in a self organizing manner--that is, with no need to assume a spectrum of time delays or to custom-design the circuit. PMID- 7863331 TI - Molecular cloning and characterization of an inner ear-specific structural protein. AB - Molecular biological studies of the mammalian inner ear have been limited by the relatively small size of the sensory endorgans contained within. The saccular otolithic organ in teleostian fish is structurally similar to its mammalian counterpart but can contain an order of magnitude more sensory cells. The prospect of the evolutionary conservation of proteins utilized in the vertebrate inner ear and the relative abundance of teleostian saccular sensory tissue made this an attractive system for molecular biological studies. A complementary DNA obtained by differential screening of a saccular complementary DNA library was identified that encodes an inner ear-specific collagen molecule. PMID- 7863332 TI - Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation. AB - Apolipoprotein E (apoE) deficiency causes severe hyperlipidemia and atherosclerosis in humans and in gene-targeted mice. Although the majority of apoE in plasma is of hepatic origin, apoE is synthesized by a variety of cell types, including macrophages. Because macrophages derive from hematopoietic cells, bone marrow transplantation was used to examine the potential of apoE synthesized by bone marrow-derived cells to correct the hyperlipidemia and atherosclerosis caused by apoE deficiency. After transplantation of bone marrow from mice with the normal apoE gene into apoE-deficient mice, apoE was detected in serum and promoted clearance of lipoproteins and normalization of serum cholesterol levels. ApoE-deficient mice given transplants of normal bone marrow showed virtually complete protection from diet-induced atherosclerosis. PMID- 7863333 TI - Retinal representations. PMID- 7863334 TI - Biotechnology regulation. PMID- 7863335 TI - AIDS proposal. Group for the Scientific Reappraisal of the HIV/AIDS Hypothesis. PMID- 7863336 TI - Clinical trials. Fisher clashes with NCI--again. PMID- 7863337 TI - Global warming. If the mercury soars, so may health hazards. PMID- 7863338 TI - AIDS mood upbeat--for a change. PMID- 7863339 TI - Cell biology. Cell cycle inhibitors may help brake growth as cells develop. PMID- 7863340 TI - Tepid endorsement for HIV vaccine trial. PMID- 7863341 TI - Express yourself or die: peptides, MHC molecules, and NK cells. PMID- 7863342 TI - The chemistry of John Dalton's color blindness. AB - John Dalton described his own color blindness in 1794. In common with his brother, he confused scarlet with green and pink with blue. Dalton supposed that his vitreous humor was tinted blue, selectively absorbing longer wavelengths. He instructed that his eyes should be examined after his death, but the examination revealed that the humors were perfectly clear. In experiments presented here, DNA extracted from his preserved eye tissue showed that Dalton was a deuteranope, lacking the middlewave photopigment of the retina. This diagnosis is shown to be compatible with the historical record of his phenotype, although it contradicts Thomas Young's belief that Dalton was a protanope. PMID- 7863343 TI - Geriatric principles of treatment applied to medical oncology: an overview. PMID- 7863344 TI - Cancer and the Older Patient. Symposium proceedings. Seattle, Washington, June 6, 1994. PMID- 7863345 TI - Rationale for the use of mitoxantrone in the older patient: cardiac toxicity. PMID- 7863346 TI - Chemotherapy of breast cancer in the older patient. PMID- 7863347 TI - The use of mitoxantrone in the treatment of breast cancer. PMID- 7863348 TI - Lymphoma in the older patient. PMID- 7863349 TI - The treatment of non-Hodgkin's lymphoma with mitoxantrone-containing regimens. PMID- 7863350 TI - Age-related declines in hematopoietic reserve capacity. PMID- 7863351 TI - Cytokine use in the older patient. PMID- 7863352 TI - Cardiovascular comorbidity in the older cancer patient. PMID- 7863353 TI - Forming and reforming the market for third-party purchasing of health care. PMID- 7863354 TI - On the ideal market structure for third-party purchasing of health care. AB - The ideal market structure would give each medical care organization effective incentives to produce maximum value for money for enrolled subscribers. It should be based on integrated financing and delivery systems--partnerships that link doctors, hospitals and insurers--with per capita prepayment, with providers at risk for cost of care and cost of poor quality, publicly accountable for quality and per capita costs. The ideal market structure must be managed by active intelligent collective purchasing agents, called sponsors, that contract with health care systems and set the rules of competition. Sponsors structure and manage the enrollment process; they create price-elastic demand; they manage risk selection; and they create and administer equitable rules of coverage. Microeconomic theory tells us what sponsors should do to get the market incentives right. There is no comparable political theory to tell us how their boards of directors should be constituted. The paper offers a list of undesirable political arrangements to be avoided and some desirable features of sponsor constitutions. PMID- 7863355 TI - Forming the system of health insurance in the Russian Federation. AB - A radical reform is being prepared in the Russian Federation health care. Its major point is a transition from tax-financed national health system to social health insurance. The paper highlights the issues of forming the system of health insurance. First, the arguments for a transition to a new model of finance are discussed. Secondly, the concept of the new model and its implementation in the context of the regional experiment are addressed. A discussion of current and expected developments focuses on two major issues: monopsony or pluralistic model of third-party purchasing? What is important for forming the market of health care provision? The major argument is that a transition from a highly integrated to a contractual model may start with regional monopsony or some version of it. A pluralistic model of third-party purchasing needs a refined regulation and may not meet health policy objectives. It is also argued that on the first stage of reform implementation forming the market of health care provision is more dependent on its regulation and management than on the market structure of health care purchasing. PMID- 7863356 TI - Can competition enhance efficiency in health care? Lessons from the reform of the U.K. national health service. AB - Since 1991 the reform of the U.K.-NHS has been introduced cumulatively. Public funding of health care has been retained and the goal of the reformers is to improve the efficiency of resource allocation by creating competition on the supply side of the market. The introduction of more autonomous Trust hospitals, general practice fund holders (GPFH) and the purchase-provider divide is described. The policy contradictions in the implementation of the reforms are analysed: the incomplete utilization of population weighted funding, the absence of a strategy in the development of GPFHs which are at once the mavericks and the catalysts of change in the new structures, the poor articulation of pricing and contracting rules, the maintenance of planned labour and capital markets which facilitate cost control but frustrate resource reallocation, and the incomplete articulation of many market rules (e.g. about merger and exit). It seems that the rhetoric of the market has been submerged in legislation and managerial rules which increase the power of central government rather than delegating control to local providers and purchasers. The lessons of the U.K. reforms for future innovators in the design of health care systems are numerous. Would a new Hippocratic Oath requiring the delivery by professionals of knowledge based medicine be as efficient but have lower transactions costs than the creation of an internal market? Who should regulate the health care market and how? How can reform best be sequenced? Is reform of funding (competing purchasers) an essential ingredient in the reform process or will supply side reform alone be adequate?(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863357 TI - Reforming the Israeli health care market. AB - Israel's experience in attempting to implement a health system reform based in large measure on managed competition should provide important data to other countries considering reliance on competitive mechanisms for third-party purchase of health care. In this paper, current proposals for reform of the Israeli market for third-party purchase of health care are examined in light of ideal market structures, particularly the theory of managed competition. The relationship between the theory, the notion of a 'purchaser-provider split' and the Israeli case are explored. The current Israeli health care market, which features enrollment of 96% of the population in competing sick funds, is presented. The changes necessary to base third-party purchase of health-care on managed competition are discussed. Special conditions of the Israeli health care system likely to influence implementation of a managed competition strategy are considered. Beyond a 'purchaser-provider' split, the proposals call for other restructurings, such as a split between finance and insurance functions, which the standard theory of managed competition does not take into account. The implications of these proposals for smooth functioning of the health care market must be weighed against political and ethical considerations unique to the Israeli environment. PMID- 7863358 TI - Should catastrophic risks be included in a regulated competitive health insurance market? AB - In 1988 the Dutch government launched a proposal for a national health insurance based on regulated competition. The mandatory benefits package should be offered by competing insurers and should cover both non-catastrophic risks (like hospital care, physician services and drugs) and catastrophic risks (like several forms of expensive long-term care). However, there are two arguments to exclude some of the catastrophic risks from the competitive insurance market, at least during the implementation process of the reforms. Firstly, the prospects for a workable system of risk-adjusted payments to the insurers that should take away the incentives for cream skimming are, at least during the next 5 years, more favorable for the non-catastrophic risks than for the catastrophic risks. Secondly, even if a workable system of risk-adjusted payments can be developed, the problem of quality skimping may be relevant for some of the catastrophic risks, but not for non-catastrophic risks. By 'quality skimping' we mean the reduction of the quality of care to a level which is below the minimum level that is acceptable to society. After 5 years of health care reforms in the Netherlands new insights have resulted in a growing support to confine the implementation of the reforms to the non-catastrophic risks. In drawing (and redrawing) the exact boundaries between different regulatory regimes for catastrophic and non catastrophic risks, the expected benefits of a cost-effective substitution of care have to be weighted against the potential harm caused by cream skimming and quality skimping. PMID- 7863359 TI - Forming and reforming the market for third-party purchasing of health care: a German perspective. AB - Germany is known for its comprehensive health care coverage by sickness funds and private health insurers and its successful cost containment policy. The stabilization of health care expenditures as a percentage of GNP was enforced by five cost containment laws since 1977. The last one became effective in 1993 and the next ones are planned for 1996 and 2000. The 1993 law has initiated drastic changes of the system. Office based physicians will be paid by a mixture of capitation, fee-for-service and fees for combined service packages. The hospital financing will be transformed from the current per diem remuneration to a payment system where per diems are combined with payments based on diagnostic related groups and patient management categories. Up till now many restrictions exist for insurees to switch sickness funds. These limitations were removed by the 1993 law. To allow unbiased competition between sickness funds, a risk compensation pool, some kind of statutory reinsurance, will transfer financial resources from sickness funds with good risk structure to those with many bad risks. In many respects health policy has imposed what health economists have recommended for a long time. However, there is some doubt whether increased competition will really increase efficiency of providing medical care because it takes place in a highly regulated market. PMID- 7863360 TI - The role of the sickness funds in the Belgian health care market. AB - This article reviews some of the salient features of the Belgian health care finance and delivery system. Special attention is paid to the role played by the third-party payers, i.e. the Health Insurance Associations (HIAs) in administering the compulsory national health insurance program. It is shown how, despite extensive government regulation, the markets for GP, specialist and hospital services exhibit fierce competition of the non-price variety. Next, the paper considers the three problems perceived to be the most pressing ones at present: (i) the problem of raising sufficient revenues to cover the public share of health expenditures; (ii) the (related) cost containment problem; and (iii) the problem of ensuring efficiency through appropriate incentive mechanisms. Finally, two recently proposed options for reform are discussed and complemented with a third proposal based on the ideas of regulated competition. It is concluded that strengthening the role of the third-party payers remains crucial in any attempt to reshape the system to make it efficient and affordable while keeping it equitable. PMID- 7863361 TI - The psychosocial issues of women serving time in jail. AB - Two hundred and one randomly selected female inmates incarcerated at a municipal jail were interviewed to establish the needs of this population and to formulate appropriate rehabilitative interventions. Measures of social support for this sample were uniformly low. Scores on the Global Severity Index of the Brief Symptom Inventory showed that 64 percent of the women were in the clinical range for mental health problems. Scores obtained from the Short Drug Abuse Screening Test indicated that 83 percent of the women were in the substance abuse range. When child and adult sexual abuse were combined, 81 percent of the women had been sexually victimized at some time in their lives. The data point to the need for improved programs and conditions within penal settings and for intermediate sanctions for nonviolent female offenders. Such sanctions could include both correctional day treatment and community-based correctional living sites. PMID- 7863362 TI - Posttraumatic stress symptomatology: similarities and differences between Vietnam veterans and adult survivors of childhood sexual abuse. AB - Social workers have identified an association between a history of childhood sexual abuse and impairment in emotional, behavioral, cognitive, and interpersonal functioning in adult survivors. This article examines similarities and differences in posttraumatic stress symptomatology between Vietnam veterans and adult survivors of childhood sexual abuse. Results indicate that the two groups were similar in that they both scored in the direction suggestive of posttraumatic symptomatology on various measures. Significant differences were found on only one measure. Content analysis also revealed differences in identification of stimuli that evoked anxiety. Examination of qualitative data provided further support for a conceptual model using a cognitive perspective. Overall, results indicated that childhood sexual abuse can be considered a traumatic event that can result in symptoms similar to those demonstrated by individuals who have experienced war-related trauma. Implications for social work practice, policy, and education are discussed. PMID- 7863363 TI - Morning support group: use of a triweekly support group in outpatient treatment of chemical dependence. PMID- 7863364 TI - Solution-focused group therapy. PMID- 7863365 TI - Social workers and HIV-affected families: is the profession prepared? PMID- 7863366 TI - Research and respectability: readers respond. PMID- 7863367 TI - Research and respectability: readers respond. PMID- 7863368 TI - Congratulations and caveats. PMID- 7863369 TI - Working with resistant drug abusers. AB - Despite the social turmoil created by drug abusers who are resistant to treatment, very little has been done to develop techniques for working with them. This article identifies some of the more promising approaches in the literature. Among these are individualized and objective feedback on the social and physiological effects of drug consumption. Expert advice to quit and the deliberate manipulation of environmental contingencies by workers can also be effective, as can partner interventions such as reciprocity marriage counseling and reinforcement training. Resistant drug abusers are of particular interest to social workers, who frequently encounter drug addiction in the context of some other, often more pressing, social crisis such as domestic violence or homelessness. PMID- 7863370 TI - Issues in serving the forensic client. AB - In the course of a study of a team model of intensive case management for people with serious mental illness who are homeless and leaving Philadelphia jails, several issues regarding the interaction of mental health and jail systems have arisen. Among these issues are continuity of care in an unpredictable jail system, extensive involvement of family members in the charges brought against clients, and the use of legal sanctions toward therapeutic outcomes. This article discusses these issues both as they have appeared in the literature and as they have affected the progress of the study. Implications for community mental health system interactions with jails in serving forensic clients are explored. PMID- 7863371 TI - Traumatic event debriefing: service delivery designs and the role of social work. AB - Traumatic events are incidents that lie outside the range of usual human experience and are so powerful that they are capable of overwhelming any person's normal coping abilities and causing severe stress reactions. Traumatic event debriefing (TED), conducted 24 to 72 hours after exposure to the traumatic event, uses a form of intensive group crisis intervention. The method is designed to help reduce acute stress symptoms and accelerate the recovery process, thereby diminishing the subsequent development of posttraumatic stress disorder. Social workers have the precise constellation of skills, social-environmental perspectives, and practice methodologies indispensable both to developing TED teams and to leading the debriefings. This article addresses the evolution of debriefing-type psychological interventions for trauma victims, the debriefing process itself, three environment-specific debriefing team designs, and the unique qualifications of social workers to develop and lead the teams. PMID- 7863372 TI - Gender differences in drug addiction and treatment: implications for social work intervention with substance-abusing women. AB - This article draws on current addiction research to describe the unique characteristics and treatment needs of chemically dependent women and how they differ from those of chemically dependent men. It explores similarities between women who are drug addicted and all women who experience gender-based oppression. The authors suggest that drug use is a coping strategy that some women adopt to manage this oppression. Finally, the article looks at traditional drug treatment programs, which have been designed to treat male addicts and fail to address the treatment needs of women. The authors offer an alternative treatment model designed to meet those needs. Parallels between characteristics of this alternative treatment model and social work practice are drawn, and opportunities and strategies for social workers to intervene with female addicts are identified. PMID- 7863373 TI - Searching for solutions to alcohol and other drug abuse during pregnancy: ethics, values, and constitutional principles. AB - Recent efforts to develop legal mechanisms to detect prenatal substance abuse and force pregnant women into drug-free conditions have precipitated ethical struggles for social workers. This article reviews relevant social work values and ethical issues, particularly the need to balance obligations to promote client self-determination, privacy, and access to chosen services with professional values that support coercive intervention to aid vulnerable people and to protect life. The constitutional principles that most affect coercive interventions--due process and equal protection--are reviewed. Recommendations are offered to guide ethical and legal social work for case interventions and policy development. PMID- 7863374 TI - Parenting groups for recovering addicts in a day treatment center. AB - This article describes parenting groups that were conducted at a day treatment center in New York City from 1989 to 1992. The population consisted of parents who were recovering from substance and alcohol addiction with backgrounds of poverty, educational deficits, and intergenerational addiction. The approach combined brief dynamic group therapy with the learning of child development, communication skills, and family management concepts in a psychoeducational model. Empathy and respect for the struggle of the recovering addict characterized the group culture and the stance of the group leader. The methodology included creative writing through group process, role playing, and values clarification activities. The high number of parenting group graduates who also completed the day treatment program suggests that parenting groups were a significant component in the recovery process. Clients in the groups reported feeling better about themselves as parents and were able to express more positive feelings toward their children. PMID- 7863375 TI - Injection drug users, crack-cocaine users, and human services utilization: an exploratory study. AB - Estimates of the number of people addicted to heroin and cocaine run into the millions. How these drug abusers interact with the social services system is not well understood. To gain insight into the nature and extent of such interactions, an exploratory study was conducted to gather information on the perceptions and utilization of human services by 44 drug abusers not in treatment. Twenty-nine injection drug users and 15 crack-cocaine users participated in focus group sessions and structured interviews. Participants were recruited by indigenous outreach workers in Dayton and Columbus, Ohio. Findings revealed a very high rate of service use by the drug users. The results raise questions about the role and efficacy of the social services system in identifying drug users and addressing their needs. In addition, the findings raise perplexing questions regarding the effectiveness of acquired immune deficiency syndrome risk-reduction efforts among injection drug users and crack-cocaine users. PMID- 7863376 TI - Multiple stressor debriefing and the American Red Cross: the East Bay Hills fire experience. AB - Workers who are mobilized to help with disaster relief are exposed to a multitude of stressors. Debriefing may prevent or minimize the negative consequences of stress reactions in relief personnel. The multiple stressor debriefing (MSD) intervention promotes the discussion of troubling aspects of the disaster work in a group format. This article discusses two models of debriefing and describes how the MSD model was used with American Red Cross personnel during the East Bay Hills firestorm in California. Specific recommendations are made for debriefing in large-scale, long-term disaster relief efforts. PMID- 7863377 TI - Skills-training groups to reduce HIV transmission and drug use among methadone patients. AB - Although methadone maintenance may be one of the more effective means of slowing the spread of human immunodeficiency virus among intravenous drug users, methadone patients continue to engage in high-risk behavior. Opiate relapse, alcohol and cocaine use, program attrition, and sexual risk-taking all present serious challenges to methadone maintenance treatment programs. These concerns underscore the need for enhancing the nonpharmacological elements of methadone clinics. This article describes the components and process of a skills-building intervention designed to reduce relapse, program attrition, and high-risk behavior in methadone-maintained populations. The authors offer a research agenda for determining whether the skills-building approach is feasible and efficacious in community- and hospital-based methadone clinics. In learning from social workers and other helping professionals, it is hoped that investigators will be able to recast and retest models that will be useful in freestanding clinical settings. PMID- 7863378 TI - [The ABO group system in tissues in advanced post-mortem changes]. AB - Post-mortem changes and in particular putrefaction makes examination of the group properties of the ABO system in tissues difficult and even more so the interpretation of results. Hitherto traditionally used serological methods, i.e. the absorption elution test and the saturation method, do not always provide sufficient data for a final evaluation. The quoted examples from practice are in favour of a combination of the traditional serological approach (absorption elution test) and the immunohistological technique (indirect immunoperoxidase reaction). PMID- 7863379 TI - [Burns caused by electrical current injuries]. AB - A group of patients who died after thermal injuries was compared with those who died as a result of burns caused by electric current. Attention was focused on the survival time and the most frequent complications. In those who died as a result of electric current the mean survival period was shorter. More frequent complications were pneumonia, shock, severe dystrophic changes of parenchymatous organs, necrosis of the heart muscle, venous thrombosis and embolism of the pulmonary artery. PMID- 7863380 TI - [Personal experience with detection of myoglobin in the myocardium using the immunoperoxidase method]. AB - The authors used the immunohistochemical reaction with antibodies against myoglobin of the heart muscle in three groups of suddenly deceased subjects with a macroscopically apparent myocardial infarction and revealed focal disappearance of myoglobin in 90%. In the second group of sudden deaths with advanced atherosclerosis without a macroscopically apparent infarction, without a macroenzymatic reaction and without any positive histological finding a disseminated reduction up to complete disappearance of myoglobin from cardiac muscle fibres was observed in 70%. In the third control group of subjects who died from a violent death without advanced coronary atherosclerosis a disseminated reduction or disappearance of myoglobin was recorded only in 26%, and this was the case where death was preceded by massive suffocation. The immunochemical method for detection of myoglobin is very sensitive. Disappearance or reduction of myoglobin in myocardial muscle fibres occurs not only in ischaemic but also in hypoxic conditions. PMID- 7863381 TI - [Hyaluronan: biology and its application for intraarticular injection]. PMID- 7863382 TI - [Study on Japan Rheumatism Association diagnostic criteria for early rheumatoid arthritis--2. Proposed diagnostic criteria for early rheumatoid arthritis]. PMID- 7863383 TI - [Amyloidosis in rheumatoid arthritis--clinical study of 124 histologically proven cases]. AB - The diagnosis of secondary amyloidosis due to rheumatoid arthritis (RA) was confirmed by positive tissue staining using Congo-red and antiserum to amyloid A protein. Biopsied specimens were obtained mainly from gastro-intestinal tracts; small salivary glands of the lips as well as abdominal adipose tissues were also studied in a small number. The results were as follows: 1. Gastro-intestinal fiberscopies and biopsies were performed on 789 RA patients for the purpose of routine screening and follow-up for amyloidosis. Seventy-seven cases (10.5%) turned out positive for amyloid. Among the biopsied specimens taken from three different sites, the proportion of amyloid-positivity was 68.9% for gastric antrum, 76.5% for duodenal cap and 88.6% for the second portion of the duodenum, suggesting the higher sensitivity and efficacy of duodenal biopsy in studying secondary amyloidosis in RA. 2. 124 patients of RA complicated with secondary amyloidosis were studied clinically with special reference to its clinical characteristics and prognosis. (1) The mean duration of RA at diagnosis of amyloidosis was 15.4 years and all patients but two were in stage III or IV (Steinbrocker). (2) Gastro-intestinal symptoms were present in 58.1% of the cases, abnormal renal signs in 58.9%, cardiac symptoms in 39.5%, respectively. All of these findings had a significant association with poorer prognosis in secondary amyloidosis due to RA. (3) The 4-year survival rate of all the cases was 57.8%, while the 3-year survival rate for the group without symptoms and signs about amyloidosis was 100%. (4) The causes of death in 36 cases were renal failure (14 cases), infection (13 cases), cerebral bleeding (2 cases), myocardial infarction (1 case), pulmonary infarction (1 case), suicide (1 case) and unknown (4 cases). Patients with intractable diarrhea were mostly susceptible to the ensuing fatal bacterial infection. PMID- 7863384 TI - [Mixed connective tissue disease in childhood]. AB - To characterize the clinical features of mixed connective tissue disease (MCTD) in childhood, 23 reported cases in Japan were analyzed for their symptoms and signs, and laboratory data. The earliest onset of the disease was found in 5 years of age, and the number of patients were increased with age. Over 80% of patients was girls. Raynaud's phenomenon preceded in most patients to the increased disease activity manifested by spiky fever, arthritis, skin rashes, and myositis. The characteristic laboratory findings were demonstrated by anti nuclear antibody (speckled type), anti-RNP antibody, rheumatoid factor, and marked hyper-gammaglobulinemia. The overall prognosis was fairly good. But cardiac involvement was the most serious problem in the early stage of the disease, and a very few children was accompanied with renal disorders. The central nervous system was rarely involved. As the long term follow-up of the children was not accomplished yet, pulmonary fibrosis or pulmonary hypertension was left for the further documentation. PMID- 7863385 TI - [Thermographic assessment of Raynaud's phenomenon in childhood mixed connective tissue disease]. AB - To assess Raynaud's phenomenon objectively, thermographic estimation of hands and fingers was performed before and after the disease- and Raynaud's phenomenon directed therapy in 3 children with mixed connective tissue disease. All the cases were positive in Raynaud's phenomenon, and the surface temperature of their hands and fingers were decreased even before cold challenge. After the cold provocation test at 4 degrees C for 10 sec., the temperature of all or some of the fingers were rapidly decreased, and the recovery of surface temperature of these fingers were markedly delayed. Even after methylprednisolone pulse therapy the pattern of the finger temperature were essentially unchanged, suggesting that steroids are not effective in the treatment of Raynaud's phenomenon. The long term administration of vitamin-E, oral prostaglandin E1, and/or serotonin receptor inhibitor were also proved to be not beneficial in improving Raynaud's phenomenon. Thus, thermography is useful in diagnosing Raynaud's phenomenon objectively, in determining the efficacy of anti-Raynaud drugs, and in estimating long-term course of the phenomenon. PMID- 7863386 TI - [Clinical significance of anti-cardiolipin antibody in patients with systemic lupus erythematosus (SLE)]. AB - Anti-cardiolipin antibody (aCL) in SLE patients reacts with cardiolipin/beta 2 GP1 complex. In order to disclose clinical significance of aCL in patients with SLE, aCL was determined by newly-developed anti-CL.beta 2-GP1 kit [Yamasa] EIA in 58 patients with SLE and the relationship between clinical manifestation of SLE and the presence of aCL was examined. Anti-cardiolipin antibody was positive in 20 patients (34.5%). In 20 SLE patients with positive aCL, livedo reticularis in 7, retinal vein thrombosis in 3, thrombophlebitis in 3 and other vasculo occlusive episodes were observed as a characteristic clinical features of positive aCL. In contrast, a SLE patient complicated by ileal perforation due to necrotizing angiitis had negative aCL. Other clinical and laboratory features associated with aCL include recurrent fetal loss and thrombocytopenia. PMID- 7863387 TI - [The significance of HLA DR6 and DR8 among patients with rheumatoid arthritis]. AB - Among 380 patients with rheumatoid arthritis (RA), there were 63 cases who had HLA DR4 without any other counterpart DR type (Group DR4.*), 30 with DR6 but without DR4 (Group DR6.DR4-), 37 with both DR6 and DR4 (Group DR6.DR4+), 34 with DR8 but without DR4 (Group DR8.DR4-), and 15 with both DR8 and DR4 (Group DR8.DR4+). 53, 29, 32, 32, or 13 female RA patients respectively from Groups DR4.*, DR6.DR4-, DR6.DR4+, DR8.DR4-, or DR8.DR4+ were investigated for the severity of their disease. 40 joints in 18 patients, 2 in 1, 19 in 8, 13 in 6, or 10 in 4 respectively from Groups DR4.*, DR6.DR4-, DR6.DR4+, DR8.DR4-, or DR8.DR4+ had had the previous history of total joint replacement operations for the diseased hips (THR) or knees (TKR). The number of cases (p < 0.01) or that of joints (p < 0.001) was significantly less among Group DR6.DR4- patients than the corresponding figure among Group DR4.* patients. Significantly smaller (p < 0.02) number of cases with DR6 (Groups DR6.DR4- and DR6.DR4+ combined) had experienced THR's and/or TKR's than those in Group DR4.*. Group DR8.DR4- patients had undergone THR/TKR operations in smaller number of the joints (p < 0.05) in comparison to Group DR4.* patients, though the difference was not significant when the numbers of operated cases were compared between the Groups. The age at RA onset among Groups DR4.*, DR6.DR4-, DR6.DR4+, DR8.DR4-, or DR8.DR4+ was 38.5 +/- 14.2 (mean +/- SD) years, 46.6 +/- 12.2, 41.7 +/- 11.7, 44.9 +/- 13.1, or 40.8 +/- 10.2 respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863388 TI - [Nephropathy in patients with mixed connective tissue disease]. AB - The first report of mixed connective tissue disease (MCTD) was described that nephropathy was rare complication of the patients with MCTD. Recently, some authors reported that the nephropathy was 25-50% of patients with MCTD. This report investigated the histopathological findings of patients with MCTD. This study was conducted on 17 patients associated with MCTD. In clinical features, there were six of nephrotic syndrome and two of hematuria and proteinuria. They were normal renal function, expect for one case (case MF). In pathological findings, there were four of membranous nephropathy, two of mesangial proliferative glomerulonephritis, including one of IgA nephropathy, and 11 of minor glomerular abnormality. Three cases translated to systemic lupus erythematosus (SLE) during follow-up period (1 to 5 years). They had hypocomplementemia and membranous nephropathy in common. In conclusion, the nephropathy is not rare complication in patients with MCTD. Sex of the 17 patients (35.3%) with MCTD have nephropathy. MCTD cases with immune-complex glomerulonephritis are likely to transit from MCTD to SLE. PMID- 7863389 TI - [Thrombotic thrombocytopenic purpura (TTP) observed in a patient with primary antiphospholipid antibody syndrome]. AB - Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome of unknown etiology and has a high mortality rate. TTP is characterized by a pentad of clinical findings, including microangiopathic hemolytic anemia, thrombocytopenia, renal abnormalities, neurologic signs and fever. The pathological feature of TTP consists of disseminated microvascular platelet thrombi. We describe a case of TTP with primary anti-phospholipid syndrome. A 27-year-old woman developed TTP in her second trimester of pregnancy. She presented with classical symptoms of TTP with compatible renal biopsy findings. Although four articles of SLE criteria (1982 ARA) were fulfilled, three of them were considered to be derived from multiple thrombosis except for a positive antinuclear antibody. Positive antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibody) with SLE-like findings suggested the diagnosis of antiphospholipid antibody syndrome rather than SLE. Although TTP has been described in patients with SLE and they can share common clinical and pathological features, the relationship between these two diseases is controversial. Many theories have been proposed to explain the nature and cause of intravascular platelet aggregation in TTP. But the pathogenesis of TTP is still unclear. This case suggests an important causal relationship between antiphospholipid antibodies and TTP during pregnancy. In TTP patients who also have SLE or SLE-like features, the antiphospholipid antibodies may have a role in the development of multiple microthrombosis. PMID- 7863390 TI - [Familial Behcet's disease--a case report]. AB - We reported a case of mother and child affected with Behcet's disease. Both had recurrent oral ulcer, erythema nodosum and arthralgia. Neither had gastrointestinal manifestation nor central nervous system involvement. The mother represented positive pathergy test, but the child did not. Laboratory data suggested no severe sign of inflammatory reaction and increased levels of immunoglobulin D. She was diagnosed as incomplete form, and he was diagnosed as suspicious form of Behcet's disease. On HLA examination, they had common haplotypes of HLA A24, B61, Cw1 and DR8. Additionally, haplotypes of HLA B7, Cw7, DR1, DQ1, were also detected in the mother, and HLA A2, Cw3, DR12, in the child. HLA-B51, which is primarily associated with Behcet's disease, was failed to be demonstrated. Familial involvement of Behcet's disease were described in only 20 cases, 11 of which had positive HLA B51. These findings suggest that molecular genetic examinations for both class I and II antigens will be necessary for a case of familial involvement. PMID- 7863391 TI - [Imaging modalities in rheumatoid arthritis]. PMID- 7863392 TI - Why viral hepatitis? PMID- 7863393 TI - Clinical and biochemical features of acute viral hepatitis. PMID- 7863394 TI - Hepatitis A. PMID- 7863395 TI - Viral hepatitis B--an overview. PMID- 7863396 TI - Hepatitis C--a South African perspective. PMID- 7863397 TI - Hepatitis E. PMID- 7863398 TI - Hepatitis viruses and hepatocellular carcinoma. PMID- 7863399 TI - The laboratory diagnosis of acute viral hepatitis. PMID- 7863400 TI - Chronic hepatitis. PMID- 7863401 TI - Management of chronic hepatitis B and C. PMID- 7863402 TI - Blood transfusion and hepatitis viruses. PMID- 7863403 TI - Liver transplantation for viral hepatitis--which patients will benefit? PMID- 7863404 TI - The doctor with hepatitis B--some legal issues. PMID- 7863405 TI - The prevention of hepatitis. PMID- 7863406 TI - "For the love of Greek". PMID- 7863407 TI - Anatomic basis of venous drainage in gastric tubular esophagoplasty. AB - This study was made with the aim of specifying the general architecture of the venous system of the stomach and its mode of drainage under normal conditions, and also of investigating the role of the venous drainage in the origin of disunion, anastomotic fistula and structure after tubular esophagoplasty pedicled on the right gastroepiploic vessels. Sixty stomachs removed from fresh cadavers were studied by injection-corrosion, using colored Altufix P10 as the injection mass. 35 specimens were injected globally via the superior mesenteric v., 15 by the same route but after clamping of the splenic, left gastric and right gastric vv., which corresponds to the technique of gastrolysis performed in esophagoplasty, and 10 were injected simultaneously with media of four different colors via the left gastric, right gastric, superior mesenteric and splenic vv. to define their respective territories. Also studied were the origin, course, termination, territory and caliber of the main gastric veins. Analysis of the results confirmed the richness of the venous anastomoses of the stomach, effected on the one hand between the two extraparietal arches at the greater and lesser curvatures, and on the other by intraperitoneal communications arranged perpendicular to these two arches. It emerges that the right gastroepiploic v. cannot always ensure drainage of the entire stomach. The factors involved are discussed. The risk of venous stasis in gastric esophagoplasty must always be borne in mind. PMID- 7863408 TI - Anatomic basis of lymphatic spread of lung carcinoma to the mediastinum: anatomo clinical correlations. AB - Correlation of the anatomic and surgical features in 360 cadavers and in 260 patients operated for bronchial carcinoma reveals that the lymphatics of the lung reach the ipsilateral mediastinum, sometimes directly and sometimes by sites which do not correspond to the anatomic site of the injection or of the pulmonary lesion. This implies the need for systematic eradication of all the lymph nodes of the ipsilateral mediastinum during surgery for bronchial carcinoma. In cases of tumoral lesions (N2), the prognosis is better when only one site is involved, whether the nodal disease is microscopic, uni- or multiglandular, with or without rupture of the capsule and whatever treatment is carried out, even when resection seems macroscopically complete to the surgeon. This is explicable in the light of the anatomic study, which shows that the lymph node chain is a functional entity which channels the lymph into the systemic circulation, either at the venous confluence of the neck or into the thoracic duct in the mediastinum. When only a single chain is affected, there is a greater than 70% chance that systemic metastases are already present, 90% when N2 affects 2 chains, while in N3 cases (lymph passage to contralateral chains) the incidence reaches virtually 100%. However, macroscopically satisfactory excision allows management of the local problem, and involvement of the mediastinal nodes, even with capsular rupture, cannot be considered as a contraindication in the absence of clinically detectable systemic metastases. PMID- 7863409 TI - The anatomy of the segmental latissimus dorsi flap for reconstruction of facial paralysis. AB - The latissimus dorsi m. and its segmental vascularity were observed in 66 specimens. The segmental arteries were found to be regularly distributed within the muscle, making it possible to design 4-6 segmental flaps. Of these the lateral 3rd or 4th is the thinnest and has the longest vascular pedicle. PMID- 7863410 TI - Anatomic and radiologic bases of combined transplantation of liver and small intestine in the pig. AB - In order to assess the tolerance induced by hepatic transplantation in a multivisceral graft, a model of a transplant combining the liver and small intestine was developed in the pig, using animals of Large White Isogroup O, typed in the system of major incompatibility as "Swine lymphocyte antigen" (SLA), whose weight varied from 30 to 40 kg. In order to limit the duration of warm ischemia, dissection of the graft was performed on the donor animal with respect for the following anatomic features: absence of intestinal attachment to the posterior parietal peritoneum, anti-clockwise torsion of 360 degrees of the intestine around the superior mesenteric a. with the small intestine convolutions on the right and the colonic helix on the left. The bifid pancreas follows this rotation and its resection must respect the vascularisation of the proximal small intestine; the hepatic a. arises from a common trunk with a gastrosplenic branch of the aorta between the crura of the diaphragm and travels sagittally from behind forward toward the liver pedicle, which it reaches ar the upper border of the duodenum; the hepatic a. and its branches are dorsal in relation to the portal vein; the hepatic arterial distribution follows a right-left and antero posterior systematisation for the six hepatic lobes of this quadruped animal. PMID- 7863411 TI - The surgical anatomy of the superior gluteal nerve and anatomical radiologic bases of the direct lateral approach to the hip. AB - In view of the increasing popularity of the direct lateral approach to the hip joint for hemi- or total hip arthroplasty, the location of the superior gluteal nerve (SGN) was studied. This nerve is in danger when using a transgluteal incision. In 20 embalmed specimens the relation of the SGN to the tip of the greater trochanter (TT) was studied as well as the relation to the iliac crest. For this purpose macroscopy, microscopy and CT were used. In 13 hips a so-called most inferior branch was found at an average of 1 cm distal to the inferior branch, the main trunk of the nerve. There was substantial variation in the course of both the inferior and the most inferior branch of the SGN. In order to prevent nerve damage, proximal extension of the transgluteal incision should be limited to 3 cm cranial to TT. Furthermore the incision has to be confined to the distal one third of the distance TT-iliac crest. In tall people extra care should be taken. PMID- 7863412 TI - Functional anatomy of the retro- and suprahepatic portions of the human inferior vena cava and their main affluents. AB - The arrangement of muscle, collagen and elastic fibers was studied in the retro- and suprahepatic (subdiaphragmatic) portions of the inferior vena cava, the hepatic veins and their main affluents. Distinctive features of the longitudinal and transverse muscle bundles are described. In these portions of the vena cava, both bundle systems are clearly separate and any continuity was observed only at the entrances of the hepatic veins. A musculo-venulolymphatic complex was noted in spurs formed by the vascular junctions. The hepatic veins and their main affluents exhibit an elliptical contour in transverse section, which apparently results from cranial and caudal thickenings of the longitudinal muscle layer. Many of these bundles are in continuity with those of the transverse muscle layer. Terminal elastic tendons were rarely observed in connection with muscle fibers of the inferior vena cava and are not present in the hepatic veins and their main affluents. In terms of form and function, the relatively thin muscular layer has a dilating action on the hepatic venous system because of the external fixed insertion point of the muscle bundles. Such an arrangement and a "polar" disposition of the muscle bundles in the hepatic venous system may assists in "suction" of the blood toward the heart. A sphincteric control of the ostia by means of crossed muscular loops supported by venulo-lymphatic micropads is a possibility. PMID- 7863413 TI - Variations of the area and shape of the left atrioventricular valve and its cusps and leaflets. AB - Measurement of the areas of the cusps and leaflets of the left atrioventricular valve (LAV) and a study of their shape were performed in 91 normal human hearts, to assess the range of variation and determine the most frequent morphologic pattern. The average areas were as follows: LAV, 904.9 mm2; anterior cusp, 447 mm2; posterior cusp, 457 mm2; anterolateral leaflet, 118.6 mm2; intermediate leaflet, 212.7 mm2; and posteromedial leaflet, 126 mm2. The commonest shape of the leaflets of the posterior cusp, proved to be rectangular. PMID- 7863414 TI - Coronary arterial territories of the left ventricle: extension and exclusivity. AB - Ninety human hearts obtained from autopsies were used. The methods applied were post-mortem angiography, dissection and the construction of an arterial map by segments, according to the classification of Selvester et al. It was shown that the arteries which have the greatest extension are the anterior interventricular and circumflex aa., while irrigation by the right coronary artery is only moderate, except in the segments of the inferior wall. Differences in the perfusion territories of the main coronary arteries and between the patterns of arterial irrigation of the left ventricle (segmental pattern and grouped pattern) were found. Finally, we define risk groups on the basis of the proportion of the ventricular mass irrigated by each artery, which are of practical interest from the clinical, prognostic and therapeutic points of view. PMID- 7863415 TI - Anatomic study of the lumbar region applied to multiplanar imaging techniques: importance and use of oblique vertical sections. AB - This anatomic study of the lumbar region (as defined by Rouviere [11]) applied to multiplanar imaging techniques was carried out both in the cadaver and in vivo. The cadaver study (5 cases) consisted of anatomic sections (transverse, sagittal, frontal and oblique) and computerised three-dimensional reconstructions after CT studies on subjects injected with colored and radio-opaque latex. The in vivo study (4 cases) used MRI sections and three-dimensional ultrasound sections coupled with the pulsed doppler. The spatially referenced oblique vertical sections revealed the structures from unusual aspects, situating them amidst the retroperitoneal area with the maximum of topographic landmarks. The transposition of these results (obtained by sectional anatomy of the retroperitoneal region) to the new techniques of multiplanar formatting after MRI, ultrasound or CT data acquisition should optimise the investigation of certain retroperitoneal structures by specifying the ideal planes of section for each organ, while diminishing certain artefacts specific to acquisitions in the traditional planes of section. Oblique vertical sections seem eminently suitable for ultrasound location of the suprarenal compartments, study of the renal pedicles and topographic retroperitoneal location. This oblique vertical visualisation constitutes a fundamental resource for the development of video-monitored surgical procedures as it corresponds exactly to the axes of the access routes in percutaneous surgery of the kidney and the adjacent anatomic structures. PMID- 7863416 TI - MR imaging of posteromedial and posterolateral stabilisers of the knee: anatomic basis and patterns of lesions in knee injuries. AB - The angular points are the ligamentous and tendinous structures that reinforce the posteromedial and posterolateral capsule of the knee and share in fixation of the posterior horns of the menisci. They are often damaged in acute injuries and this is usually associated with ruptures of the cruciate and collateral ligaments and may add to the degree of laxity. We describe the normal appearance of these structures in terms of the sectional anatomy, correlated with the lesional appearances of complete and incomplete ruptures and associated meniscal detachments as shown by clinical testing and arthrotomy findings. PMID- 7863417 TI - Three-dimensional reconstruction of a levator claviculae muscle. AB - During routine radiological examination of a 72 year-old woman a soft-tissue shadow in the left posterior triangle of the neck was observed. Three-dimensional reconstruction of this structure suggested that it might be a muscular variant: a levator claviculae muscle. In our case it took origin from the upper part of the cervical column and was inserted into the lateral third of the clavicle. With this example as a background, the general significance of anatomical muscular variants for modern imaging techniques is discussed. PMID- 7863418 TI - The secondary nasal middle concha. AB - In this study a total of 175 coronal CT scans of the nasal cavity and paranasal sinuses have been investigated. A secondary middle concha was detected bilaterally in 12 (6.8%) out of 175 patients. In all cases, the ethmoidal infundibulum was placed anteroinferior to the lateral origin of the secondary middle concha. This structure did not obstruct the osteo-meatal complex in any of the 12 cases. PMID- 7863419 TI - Mesencephalo-diencephalic angioanatomy in arteriovenous malformations. Endovascular management of transmesencephalic vs subependymal supply in 954 cases between 1982 and 1994. AB - This report presents the arteries of the mesencephalo-diencephalic region and their different role in the supply to the cerebral structures. Among them, the authors distinguish the subependymal and transmesencephalic arteries to which they pay a special attention since these vessels present a specific angiographic aspect. The importance of their differentiation is emphasized. The authors discuss the management of subependymal and (trans)mesencephalic arteries during endovascular neuro-intervention illustrative cases. PMID- 7863420 TI - A case of bilateral anomalous origin for dorsalis pedis arteries (anomalous dorsalis pedis arteries). AB - A case of bilateral anomalous arterial supply of the lower limb is presented. In this case, both anterior tibial arteries were hypoplastic. These arteries came to the anterior (extensor) compartment by passing superiorly through the interosseous membrane. They ran between the tibialis anterior and the extensor hallucis longus muscles and terminated after giving numerous muscular and fascial branches. The dorsalis pedis arteries originated from the peroneal arteries. The peroneal arteries reached the anterior compartment by piercing the interosseous membrane at its lower part and ran as the dorsalis pedis arteries. Awareness of the anatomical variations in anatomy of the distal popliteal artery is important for angiographers, vascular surgeons and reconstructive surgeons who operate upon these regions. PMID- 7863421 TI - Anatomic basis of vascular distribution in combined removal of liver and pancreas (28.5.93). AB - Based on the study of the arterial distribution of 120 hepatic grafts removed from brain-dead patients, the authors assess the possibilities of vascular partition in cases of combined removal of the liver and pancreas. The discussion deals with the vascular distribution of each organ. The presence of a right hepatic artery arising from the superior mesenteric a. (SMA) requires preservation of the SMA with the hepatic graft, while the pancreas is removed with the celiac trunk (CT) and its branches. The presence of a left hepatic artery arising from the CT requires its preservation with the hepatic graft, the pancreas being removed with the SMA and the splenic artery. PMID- 7863422 TI - [The use of contrast media for quality assurance in radiotherapy planning]. AB - PURPOSE: The target volume definition in radiation therapy was evidently improved by CT and MRI. Basis of treatment planning, however, remains the therapy simulator. Important instruments for adequate fluoroscopic treatment planning are contrast media that recently have been applied less out of legal and professional reasons. Aim of this work is to evaluate the possible benefit of contrast media applications. PATIENTS AND METHODS: In 1303 simulations between 1.1.1993 and 30.9.1993 105 times intravenous contrast media were applied, supplied by oral or endolymphatic contrast agents. It was studied if the previously intended plan had to be altered due to contrast media application. RESULTS: In 17 out of 105 cases (16.2%) the target volume or the preplanned technique had to be altered after contrast media application. Main reason was the existence of anatomical variations especially in kidney and small bowel detected by use of contrast agents. So standard indications for contrast media applications were defined. CONCLUSIONS: Contrast media are an important tool in treatment planning that should be orientated on diagnostical standards. Applications of contrast agents facilitate the detection of anatomical variations and the selection of the appropriate technique in order to shield sensitive tissues. The therapeutical and legal benefit outweigh potential hazards due to intolerances or professional obstacles. PMID- 7863423 TI - [Vitamin A in tumor therapy: significance of clinical and pre-clinical findings for radiologic oncology]. AB - PURPOSE: Retinoids are a class of compounds structurally related to vitamin A which have been found to be active agents experimentally as well as clinically in the prevention and treatment of tumors. The data available suggest to study whether they might improve treatment results if combined with irradiation. METHODS: The clinical results in the prevention and treatment of cancer with retinoids are reviewed. In the context of experimental studies evaluating the antiproliferative effects of retinoids, cytokines and radiation alone or in combination our own experimental investigations analyzing a combination of all trans-retinoic acid, interferon-alpha (IFN-alpha) and ionizing radiation in squamous cell carcinoma cell lines are described. RESULTS: There is a solid body of experimental and clinical data to combine retinoids with cytokines (e.g.IFN alpha). Since it is known that vitamin A alters the radiation response in experimental tumors our analyses further support the combination of retinoids and IFN-alpha with ionizing radiation. CONCLUSIONS: We emphasize further clinical investigations evaluating the combined treatment with retinoids/IFN-alpha and ionizing radiation in squamous cell carcinomas such as head and neck tumors and cervical cancer. PMID- 7863424 TI - [Tamoxifen and osteoporosis]. PMID- 7863425 TI - [Adjuvant monotherapy with carboplatin in stage I testicular seminoma]. PMID- 7863426 TI - [Tissue CEA as a prognostic factor in patients with breast cancer]. PMID- 7863427 TI - [Helicobacter pylori infection in gastric lymphoma]. PMID- 7863428 TI - [The flab method of intraoperative radiotherapy]. AB - PURPOSE: Improvement of the relapse rate by locally increasing the tumor dose. METHODS: To increase the dose in the tumor bed a method for intraoperative radiation therapy has been developed. The radiation is applied using a high-dose rate afterloading system. Flexible plastic flabs are used as applicators. Each flab contains tubes for the alterloading source. The size of the applicator is chosen to correspond to the size of the target volume. In the dosage system we use the dwell times at all source positions are equal. The dwell time has been precalculated to give the reference dose at the reference position which is located at the surface of the flab in the center of the target volume. RESULTS: The dose distributions around the flab have been calculated as a function of the thickness of the flab. If the source is not placed on a regular grid within the applicator due to a non ideal positioning of the tubes within the applicator, the dose distribution is not altered too much, if the positioning error is not larger than +/- 2 mm. The influence of a curvature of the flab has been evaluated and methods to decrease the dose at critical organs are discussed. CONCLUSION: The flab methods for IORT is safe and easy and has been demonstrated for more than 150 cases. This method allows the increase in tumor dose even in regions which are not easily treated by electron IORT due to the rigid electron applicators. Because of the rapid dose fall off, the flab method can only be used for flat target volumes like the tumor bed. PMID- 7863429 TI - [Preoperative radiochemotherapy in primary non-resectable rectal cancer]. AB - PURPOSE: In a pilot-study patients with primarily non-resectable rectal cancer received a pre-operative radiochemotherapy to assess the tolerance and efficacy of this treatment protocol. PATIENTS AND METHOD: Twenty patients with non resectable rectal cancer (Mason CS III-IV) have been irradiated from September 1989 through February 1994. The total dose, calculated at the isocenter, was 50.4 Gy with 5 fractions of 1.8 Gy per week with a small volume boost in selected cases. Chemotherapy was administered on 5 consecutive days in week 1 and 5 with 1000 mg/m2 5-FU per day as continuous infusion over 120 hours. RESULTS: The treatment was well tolerated. Acute toxicity included 1 grade III-dermatitis, 7 grade II-enteritis, 1 grade III- and 3 grade II-leucopenia. Seventeen out of 20 patients were resected 6 weeks after radiochemotherapy, 3 patients had no surgery (1 toxic death due to septicemia, 1 refusal of surgery after complete remission, 1 thrombocytopenia due to liver cirrhosis), all 3 had at least partial remission of their tumors. Fourteen out of 17 (82%) resections were curative (R0) with 1 additional R1- and 2 R2-resections. Ten out of 14 (71%) curative resected patients had no lymph node metastasis. A detailed histological examination showed regression in 15/16 tumors with fibrosis and vascular wall changes. Nine out of 16 patients had only minimal residual tumor. CONCLUSIONS: In this pilot study, pre-operative radiochemotherapy was well tolerated. The relatively high rate of curative resections and marked histological tumor regressions of this approach requires further investigations in a randomized trial. PMID- 7863430 TI - [Locally restricted dose escalation in radiotherapy of primary advanced and recurrent rectal cancers]. AB - PURPOSE: Prognosis in patients with resected rectal carcinomas is correlated to local tumor control. Percutaneous (EBRT) and intraoperative boost irradiation (IORT) can improve local control. The aim of this study was to analyse the role of locally restricted dose escalation and the possibility to integrate IORT in a multi-modality adjuvant treatment approach. PATIENTS AND METHODS: A total of 128 and 71 patients with primary and recurrent disease were eligible for analysis. More than 60% of patients suffered from a stage III carcinoma. Between 26.3 and 38.8% of patients revealed lymphangiosis carcinomatosa in pathohistological examination. A dose of 40.2 Gy was applied using multiple field techniques. Either a percutaneous boost dose of 18.3 Gy or an intraoperative boost dose of 12.1 Gy was given in 97 and 62 patients. 40 patients with non-resectable recurrent carcinomas were treated with radiotherapy alone. In respectively 67.4% and 52.6% of IORT patients (primary and recurrent) a simultaneous chemotherapy was given, whereas only 16.5% and 8.3% of patients with EBRT alone had additional chemotherapy. RESULTS: Five-year overall survival was 64% and 41% in stage II and III (T2-3) carcinomas. All patients with stage III (T4) carcinomas died within 3 years. Overall the local failure rate was correlated to tumor stage (12.7 to 19.7%) and lymphangiosis carcinomatosa (12.5 vs. 22.9%). In patients with radiotherapy alone, local failure rate decreased with increasing irradiation dose (32%/40 to 48 Gy, 25%/49 to 56 Gy, 20.5%/57 to 66 Gy 0%/40.2 Gy + IORT). The overall 2-year survival was significantly improved after IORT and IORT plus simultaneous chemotherapy in both primary and recurrent disease. Perioperative morbidity was not increased. The toxicity of the multi-modality approach with IORT was low and acceptable. CONCLUSION: The local tumor control in rectal carcinoma after radiotherapy was dose dependent, IORT could be integrated in an adjuvant multi-modality treatment concept, without increasing morbidity. Local failure rate could be markedly reduced. PMID- 7863431 TI - [Three-dimensional planned radiotherapy in rectal cancer. Feasibility study and preliminary clinical results]. AB - PURPOSE: Since 1991 the use of three-dimensional planned radiation therapy for rectal cancer was evaluated as a part of a clinical project funded by the Deutsche Krebshilfe at the Radiological Department of the University of Heidelberg. First clinical experiences are reported. PATIENTS AND METHODS: 32 patients who were irradiated loco-regional for rectal cancer were analysed retrospectively. Radiation therapy techniques: patient's position was prone by the use of a belly board. Three-dimensional treatment (3D) planning system was voxelplan. The radiation therapy was started using a 3-field-box technique modified by 3D-technique after 22 to 42 Gy, depending on therapeutic concept. RESULTS: On average 92% of the planning target volume were encompassed with the 80% isodose. The average maximum dose was 108% (isocenter = 100%), of the small bowel volume received less than 34% of the dose, 70% of the bladder volume less than 40% respectively. Total average dose was 52.4% Gy. Irregular fields were used in all patients, a non-coplanar field was used to optimize dose-distribution in 41% of the patients, 21 patients received chemotherapy simultaneously. Acute side effects according to gastrointestinal tract reached grade 1 (WHO) in 9 patients, grade 2 in 2 patients. Side effects according to bladder reached grade 1 in 5 patients grade 2 in 1 patient respectively. In 4 patients suffered from acute side effects concerning the bladder. In one patient acute side effects grade 1 concerning gastrointestinal tract was observed. Portal films were analysed to evaluate precision of radiation therapy. On average the error was 3.1/4.5/4.0 mm in the x/y/z direction respectively. The standard deviation was 4.4/6.8/6.3 mm for x/y/z respectively. A median time of 2 hours was necessary for all planning procedures. CONCLUSIONS: Three-dimensional treatment planning optimizes dose-distribution in a relevant number of patients. Its clinical use for treatment of large targets or in order to applicate high doses is justified. Planning target volume should cover the clinical target volume with a margin of 1.5 cm. PMID- 7863432 TI - [Radiosensitivity of hyperpentaploid cell clones in vulvar neoplasms]. AB - INTRODUCTION: Intension of our examination is to investigate changes in ploidy during radiotherapy and to find out radiosensitive cloni of tumors. PATIENT AND METHODS: In November 1993 a 83-year old patient with a carcinoma of the vulva was introduced to the Strahlenklinik der Stadtischen Kliniken Offenbach. It was a stage T3N0M0 tumor (UICC 1990). We performed daily smears of the tumor surface during radiotherapy. The smears became air-dried before fixation in PBS/formaldehyde and staining with the Feulgen procedure. The DNA-analyse took place at an image-analysis-system (Ahrens Cytometry Analyse System). RESULTS: Nine and 16 weeks after radiotherapy the patient showed clinically complete remission. Macroscopically and histopathologically there was no tumor found. The ploidy-analysis shows the take off of the hyperpentaploid cells on radiotherapy. Nine and 16 weeks after finished therapy there are no more hyperpentaploid cells detectable. CONCLUSIONS: The DNA-determination is a senseful completition to estimate the success of therapy. It is possible to earn informations about the behaviour of different tumor cell populations during the course of radiotherapy. The hyperpentaploid cells are a radiosensitive part of the tumor. For being able to judge about the route of this cells, if they are proliferating cells of a peritriploid tumor population, or if they proliferate themselves, are some more examinations and additional investigations necessary. PMID- 7863433 TI - [The efficacy of sirdalud in the drug therapy of pain in the spine]. AB - The activity of myorelaxant sirdalud (tizanidine) was studied in 36 patients aged 20-79 with pain syndrome (reflex muscular-tonic, myofascial, acute compression radiculopathy). The condition of the patients was evaluated according to the visual analog scale where the scores were assigned to the intensity of muscular spasm, pain at rest, exercise and at altitude tension and functional decline. Pain symptoms diminished as early as the treatment day 3. The same was true for muscular spasms. The highest effect of sirdalud occurred in acute phases of the diseases. Pain relief was so material that 20 patients were able to discontinue analgetics and tranquilizers. For 12 patients the doses of nonsteroid antiinflammatory drugs were noticeably reduced. Side effects of sirdalud were minimal: slight sleepiness and xerostomia. PMID- 7863434 TI - [The use of myolastan in athletes with myoenthetic injuries]. AB - Myolastan was given to 9 sportsmen with acute muscular injury and 5 with chronic one in addition to the standard treatment. Control subjects with similar acute and chronic injuries (7 and 3 patients, respectively) were not given the drug. The patients with acute injuries on myolastan resumed muscular exercise 4.5 weeks after the trauma, while similar controls were able to do that only 6 weeks after it. Chronic injury patients returned to their routine loads 1 week earlier than controls. Myolastan proved effective in combined treatment of acute and chronic myoenthetic damage. PMID- 7863435 TI - [The immunological aspects of the development of diabetes mellitus and its complications]. PMID- 7863436 TI - [The peroral therapy of non-insulin-dependent diabetes mellitus]. AB - The paper presents the results obtained in the treatment of 510 patients with noninsulin-dependent diabetes mellitus (NIDDM). Of them 420 received bucarban, 30 gilemal and 60 adebit. Bucarban and gilemal decreased fasting glycemia and that after the standard meal. The patients were also made less insulin-resistant. Hyperinsulinemia did not respond to the above drugs. Adebit demonstrated hypoglycemic, antihyperinsulinemic, antihyperbetalipoproteinemic and hypocholesterolemic activity. 10% of NIDDM patients developed primary resistance to oral sulfonamide drugs. In intact insulin secretion NIDDM patients were effectively treated both with sulfonamide sugar-reducing drugs and biguanid derivatives. PMID- 7863437 TI - [The use of acarbose for treating diabetic patients]. PMID- 7863438 TI - [Phosphorus-calcium metabolism and the secretion of calcium-regulating hormones in diabetic nephropathy]. PMID- 7863439 TI - [The role of Na/Li countertransport in the pathogenesis of diabetic nephropathy]. PMID- 7863440 TI - [The results of a comparative study of the lipid peroxidation processes and of the malondialdehyde level of the blood cells in patients with diabetic angiopathies and during insulin therapy]. AB - Lipid peroxidation was studied by the levels of malonic dialdehyde (MDA) in the platelets and red cells of patients with diabetes mellitus (DM) type 1 as to relationships to vascular complications and insulin therapy. MDA appeared elevated both in red cells and platelets of DM patients, but was high in red cells only in DM patients with retinopathy. Insulin therapy contributed to gradual recovery of MDA levels both in platelets and red cells of all the DM patients except those with angiopathy who retained high red cell MDA on insulin treatment week 12. This suggests the necessity of adjuvant antioxidants in insulin treatment given to DM patients with vascular complications to arrest progression of angiopathy. PMID- 7863441 TI - [A comparative analysis of the function of the autonomic nervous system in patients with thyrotoxicosis and autonomic crises]. AB - Patients with diffuse toxic goiter and those with vegetative dystonia and paroxysmal permanent disorders are shown to have parasympathetic deficiency and moderate sympathetic insufficiency. In toxic goiter patients hyperhydrosis was accompanied by normal conduction along the vegetative perspiration fibers and a significant increase in foot potential amplitude. In patients having vegetative crises there was reduced conduction along the perspiration fibers. Clinical symptoms of enhanced sympathetic activity in both the diseases can be explained by weak parasympathetic influences and hypersensitivity of peripheral tissues to catecholamines. Spilberger test ascertained high reactive and personal anxiety in both groups. By modified MMPI, toxic goiter patients are characterized by hypochondriac, depressive and anxiety trends. Patients with vegetative crises were prone to demonstrative reactions, hypochondria and anxiety. PMID- 7863442 TI - [Opioid analgesics--a differential approach to their use in patients with acute pain]. PMID- 7863443 TI - [The endocrine status of men with lupus nephritis]. AB - Renal function was assessed in 8 males at reproductive age suffering from lupus nephritis (LN). Normal renal function was registered in 5 patients, hypofunction in 3 males. Endocrinological examinations (evaluation of secondary sexual characters, of hypophyseal and sex hormone profile, sexological questionnaires, spermograms) failed to distinguish significant differences between SLE males and renal patients without SLE suffering from hypogonadism (13 males with uremic hypogonadism, 10 males with azoospermia induced by cytostatics). Endocrinological changes revealed may result from uremia and immunodepressive therapy. In 5 patients these abnormalities were corrected by parlodel and zinc sulfate. The authors came to the conclusion that feminization is not universal in LN males. PMID- 7863444 TI - [The mechanisms of the development of pregnancy complications in hypertension and glomerulonephritis]. AB - Pregnancy complications have been analyzed in 124 females suffering from essential hypertension (EH) and chronic glomerulonephritis (CGN). Such complications, as late gestosis (8.9%), ablation placentae (1.6%), premature delivery (14.5%), intrauterine growth retardation (14.5%) occurred more frequently than in population. Pre- and perinatal deaths were encountered with the same frequency as in the population. Morphologically, the placentas had in many cases histological evidence of moderate placental insufficiency (PI). In more than 60% of the patients there were uteroplacental and fetoplacental hemodynamic defects. Placental circulatory disorders and PI ran subclinically in most of the cases as they were compensated. In EH and CGN pregnant women, compared to healthy controls, red cells acquired abnormal forms more frequently, serum thromboxane B2 levels got elevated, lactate hydrogenase activity became enhanced. Erythrocytic damage and platelet activation in EH and CGN pregnant women may indirectly confirm the existence of systemic angiopathy. It is suggested that ischemic placenta may produce endothelial toxin, that systemic endothelial damage in EH, CGN, PI may be synergetic which potentiates its clinical appearance in the form of the above pregnancy complications. PMID- 7863445 TI - [The comparative efficacy of treating patients with chronic bronchitis and late pregnancy toxicosis by using different enterosorbents]. AB - Enterosorbents Polysorb MP and Polyfepan were tried in patients with chronic bronchitis in the stage of aggravation and with late gestosis. The trends in clinical and laboratory indices, in external respiration, cellular and humoral immunity, in the content of middle-weight molecules in relevant patients undergoing enterosorption with the above sorbents against the controls were more favourable. This supports validity of enterosorption in patients with chronic bronchitis and late gestosis. PMID- 7863446 TI - [The puerperal hemolytic-uremic syndrome]. PMID- 7863447 TI - [Monitoring the activity of systemic lupus erythematosus in pregnancy]. AB - To evaluate the effect of pregnancy on systemic lupus erythematosus (SLE) activity, the authors studied 35 patients with definite SLE (ARA criteria, 1982). SLE activity was estimated every trimester of pregnancy and 3-14 months after the delivery. The disease activity was judged by scores (SLEDAI, version I and II) and by an increase in prednisolone dose more than 5 mg/day. The activity score elevated in 31% (SLEDAI I) or in 17% (SLEDAI II) during pregnancy was similar to frequency of flares after the child's birth (34% or 23%, respectively). In 22 (63%) of 35 patients the steroid dosage was increased during pregnancy versus 3 (8.5%) patients postpartum. The most frequent SLE complications observed in pregnancy were renal, CNS and mucocutaneous disorders. The frequency of SLE exacerbations and outcomes of pregnancy were related to the disease activity in conception. PMID- 7863448 TI - [Thyroid diseases and pregnancy]. PMID- 7863449 TI - [Danazol in the treatment of endometriosis]. AB - 48 females with uterine endometriosis stage 1 and 2, 26 female with mild and moderate external endometriosis and 9 females with external in combination with internal endometriosis with the disease duration from 6 months to 10 years were given danazol in doses 200-400 mg/day for 6 months. The effect of the treatment proved to be very high: 37 patients were cured, 14 improved, 3 got pregnant. 11 patients needed the second treatment course. Side effects were rare. Depressed hyperactive menstrual cycle normalized quickly. It is inferred that danazol doses 200-400 mg/day are adequate for induction of complete or partial responses in internal and external endometriosis. PMID- 7863450 TI - [Diagnostic errors in cancer]. PMID- 7863451 TI - [Pain and analgesia in emergency cardiology (a lecture)]. PMID- 7863452 TI - [Lymphocytic interstitial pneumonia as a variant of a precancerous lung lesion]. AB - The paper reports a rare case of 26-year-old female with diffuse infiltrative lesions in both lungs. Blood tests revealed hypergammaglobulinemia and fast ESR. Lung biopsies exhibited diffuse lymphoid infiltration with fibroatelectasis regions. Cytological and immunophenotypic studies of the lavage showed polyclonal composition of the cell population and prevalence of mature lymphocytes. The diagnosis was made of lymphocytic interstitial pneumonia (LIP). No progression of the condition was observed. In view of expected malignant transformation the case was followed up. Benign characteristics of lymphocytic infiltration, no negative shifts within 5 years allow avoiding active immunodepressive treatment in this stage of the disease which belongs to diffuse forms of pseudolymphoma and is considered to be a prelymphomatosis status. PMID- 7863453 TI - [An evaluation of the cardioprotective action of the preparation ICRF-187 (Cardioxane) during the treatment of breast cancer with large doses of adriamycin]. AB - Twenty females with disseminated breast cancer received courses of polychemotherapy with 21-day intervals. The regimen comprised adriamycin (ADM), cyclophosphamide and 5-fluorouracil in the dose 50, 500 mg/m2, respectively. 30 minutes prior to the treatment the patients were given the cardioprotector cardioxan (1000 mg/m2). Cardiological control (ECG, EF according to echo-CG and radionuclide ventriculography, PP/EP M1/M2, T1/T2 according to echo polycardiography and Doppler cardiography) was performed before the treatment and at ADM total dose 200-300 mg/m2 followed by measurements at each dose increase by 100 mg/m2. The findings showed no evidence of ADM-related cardiac damage up to ADM dose 900-1000 mg/m2 in the case of cardioxan protection, though there was a tendency to M1/M2 increase which needs further studies as it suggests worsening of left ventricular diastolic contractility. PMID- 7863454 TI - [The pathogenesis of small-plaque parapsoriasis]. AB - The paper deals with the origin of parapsoriasis nodularis, which in its micronodular variant belongs to chronic dermatosis and has a clear-cut clinical and histological appearance. The disease arises most frequently after stress and occurs for the most part in middle-aged males. The leading role in pathogenesis of parapsoriasis nodularis is played by cellular immunity as indicated by reduced count of T-lymphocytes, active T-lymphocytes as well as the emergence of delayed hypersensitivity. PMID- 7863455 TI - [Diflucan in the treatment of fungal diseases]. PMID- 7863456 TI - [The Extencillin treatment of patients with early forms of syphilis]. AB - Outpatient treatment of syphilis was given to 250 patients. All of them received extencilline (benzathine penicillin G) in intramuscular injections. One injection of the drug (2400000 U) was administered for primary seronegative syphilis (15 cases) and for prevention (65 subjects). Two injections with 7-day interval were carried out in the dose 2400000 U for primary seropositive (58 cases), secondary early (14 cases) and recurrent syphilis (36 cases). Patients with secondary recurrent syphilis whose body mass exceeded 85 kg (55 cases) and subjects with latent disease (72 cases) received 3 injections in 7-day intervals. Extencilline proved a potent antisyphilis tool able to rapidly eliminate clinical symptoms of the disease and to promote making serological reactions negative. Extencilline activity is superior to that of bicillin and water-soluble penicillin. Treponema pallidum escape from syphilid surface within 7 treatment hours, on the average. Extencilline is worthy of being used among most effective drugs in outpatient treatment of early syphilis. PMID- 7863457 TI - [The diagnosis and treatment of neurosyphilis today]. PMID- 7863458 TI - [The antianginal efficacy of calcium antagonists in men and women at 60 and older. Approaches to predicting the effect of the preparations]. AB - 20 mg of nifedipine, 160 mg of verapamil and 120 mg of diltiazem were given to 53 patients aged 60-90 (33 males and 20 females) with stable angina pectoris and painless myocardial ischemia. Bicycle exercise tests employed to evaluate antianginal activity of the above drugs showed them to significantly prolong the period of exercise free of a 1-mm depression of the ST segment. This was true both for males and females. In females nifedipine produced the weakest effect. Anti-ischemic activity of the drugs appeared to depend on the presence of arterial hypertension and voltage signs of left ventricular hypertrophy, initial exercise tolerance and heart rate, blood triglyceride concentrations, left ventricular end-diastolic volume, the size of the left atrium, interventricular septum thickness, etc. To prognosticate the effect of each of the 3 drugs as well as nifedipine paradoxical action in some patients the authors propose to use classification trees, providing a significant branching virtually in all relevant points. PMID- 7863459 TI - [Systolic hypertension in elderly people in the practice of the district therapist]. PMID- 7863460 TI - [Ethical problems in predicting health status: the use of disease risk factors]. AB - It has been shown with special reference to the studied risk factors of coronary heart disease that at present a differentiated approach to the evaluation of epidemiological and experimental data is required. The pathogenetic interpretation of the data may seem relatively obvious, whereas the practical evaluation of individual risk of health loss and death as well as preventive measures are not effective and attractive enough for an individual subject. Introduction of individual prognosis and preventive programs should be based by means of analysis of the benefit and losses ratio due to those programs. PMID- 7863461 TI - [Ticlopidine]. PMID- 7863462 TI - [Algorithms for empirical antibiotic therapy]. PMID- 7863463 TI - Intravenous antiplatelet efficacy and safety of the platelet GPIIb/IIIa antagonist, DMP 728 in anesthetized dogs. AB - DMP 728, cyclo (D-2-aminobutyrate-N-Methyl-L-Arginyl-Glycyl-L-Aspartyl- 3-amino methyl-benzoic acid) methanesulfonate salt, is a novel antiplatelet agent with high affinity and specificity for human and canine platelet GPIIb/IIIa (alpha 2/beta 3) receptors. DMP 728 demonstrated a potent antiplatelet efficacy in inhibiting ADP-induced platelet aggregation in either human or canine PRP with an IC50 of 0.046 and 0.015 microM, respectively. The IC50 of DMP 728 in inhibiting human platelet aggregation in PRP ranged from 0.02-0.05 microM regardless of the agonist used or even their combinations. Additionally, DMP 728 displayed a much greater affinity in inhibiting 125I-fibrinogen binding to stimulated human platelets as compared to the linear peptide RGDS or fibrinogen. The present study was undertaken to examine the i.v. antiplatelet efficacy and safety of DMP 728 in anesthetized dogs. In anesthetized mongrel dogs, DMP 728 (0.001-1.0 mg/kg, i.v. bolus) produced a dose-dependent inhibition of ex vivo platelet aggregation induced by ADP. The onset of inhibition was immediate, and the duration of antiplatelet effects was dose-dependent. A maximal inhibition of platelet aggregation and a reversible prolongation of bleeding time at 0.01 mg/kg were shown. Additionally, the antiplatelet efficacy/safety of DMP 728 was examined after i.v. administration at different infusion rates ranging from 0.008 to 0.833 micrograms/kg/min for 2 hours. A minimal antiplatelet effect was observed at the 0.008 micrograms/kg/min for 2 hours, while a maximal inhibition of platelet aggregation along with a reversible prolongation of bleeding time was achieved at 45-60 min post-infusion of 0.08 micrograms/kg/min x 2 hours. Prolongation of bleeding time was significantly reduced upon the cessation of the infusion while maximal inhibition of platelet aggregation was maintained longer. At all of the above regimens, DMP 728 did not result in any significant effects on platelet counts. Furthermore, DMP 728 did not elicit any other platelet unrelated adverse effects over wide range of doses. These data suggest that DMP 728, a low molecular weight platelet GPIIb/IIIa receptor antagonist, is a potent and systemically active antiplatelet agent with reversible effects on bleeding time. PMID- 7863464 TI - Platelet aggregation, ATP release and cytoplasmic Ca2+ movement: the effects of cloricromene. AB - A placebo-controlled, double-blind, randomized, cross-over study was performed in 24 healthy volunteers. 12 volunteers received Cloricromene (100mg gastroresistant capsules twice a day) for 7 days, the other volunteers received identical placebo capsules. Subsequently, after a 7-day wash-out period, at day 15, each subject received the other treatment. Blood samples were taken on days 1 and 15 (1st day of each treatment) as well as on days 7 and 21 (7th day of each treatment) before the morning drug administration and 2 and 4 hours later. Platelet aggregation and ATP secretion were studied in whole blood (WB) using ADP and collagen as stimulating agents. Ca2+ fluxes were studied in aequorin-loaded, washed platelets stimulated with ADP and collagen, while aggregation in platelet-rich plasma (PRP) was studied using PAF, ADP and adrenaline as agonists. Consistent inhibition of aggregation and release induced by both ADP and collagen was observed in WB after Cloricromene administration. Similarly, Ca2+ flux was also inhibited after drug administration. Platelet aggregation in PRP was inhibited only after 7 days of Cloricromene treatment with ADP and adrenaline as stimuli. We conclude that oral administration of Cloricromene leads to significant antiplatelet activity in healthy volunteers, in particular when platelets are studied in the presence of other blood elements. PMID- 7863465 TI - Concentration of RGDS-containing degradation products in uremic plasma is correlated with progression in renal failure. AB - A concentration of protein degradation products containing the RGDS sequence, which could contribute to a lower reactivity of uremic platelets, has been estimated in both uremic (n = 16) and control (n = 7) plasmas. Degradation products and other small molecules were separated from plasma by filtration through AMICON YM-10 filter. RGDS antigen was determined in filtered material using the radioimmunoassay method based on monospecific anti-RGDS rabbit polyclonal antibodies. The concentration of RGDS-containing degradation products in uremic plasma ranged from 0.8 to 353 nM with mean value 58.6 +/- 24.9 nM and was higher than in control (0.7 to 5.9 nM, mean value 2.1 +/- 0.9 nM). Moreover, the level of RGDS-antigen positively correlated with plasma creatinine concentration (R = 0.87, p < 0.001). The filtered material showed an inhibitory effect on fibrinogen binding to control platelets in respect to RGDS-antigen concentration. We conclude that the elevated concentration of RGDS-containing degradation products in uremic plasma is partially responsible for bleeding tendency in renal failure. PMID- 7863466 TI - Evidence for the existence of two different ADP-binding sites on rat platelets. AB - [3H]-2-Methylthio-ADP ([3H]-2-MeS-ADP), a stable analogue of ADP bound to one type of specific binding sites on rat platelets (KD = 0.77 +/- 0.07 nM, Bmax = 160 +/- 11 fmol/10(8) cells). 2-MeS-ADP and ADP antagonized [3H]-2-MeS-ADP binding, showing respective Ki values of 1.4 +/- 0.1 nM and 486 +/- 78 nM. Clopidogrel, a potent and specific inhibitor of ADP-induced platelet aggregation partially inhibited (approximately 70% inhibition) the binding of [3H]-2-MeS-ADP at the same time it abrogated 2-MeS-ADP- and ADP-induced adenylyl cyclase inhibition and aggregation. A population of clopidogrel-resistant [3H]-2-MeS-ADP binding sites was detected on platelets from treated animals. These receptor sites (KD = 0.9 +/- 0.2 nM, Bmax = 47 +/- 5 fmol/10(8) platelets) which showed high affinity for both ADP and 2-MeS-ADP (Ki values in the nanomolar range) might be involved in the ADP-induced shape change, a clopidogrel-resistant ADP-induced event. Using clopidogrel which acts via a direct and irreversible inhibition of ADP binding to its adenylyl cyclase-coupled receptor sites on platelets, we were able to discriminate between two types of ADP receptor sites. The former which was clopidogrel-sensitive represented about 70% of the total [3H]-2-MeS-ADP receptors and was responsible for ADP-induced platelet aggregation and adenylyl cyclase inhibition. The latter which was not affected by clopidogrel might be involved in ADP-induced shape-change. PMID- 7863467 TI - Kinetic analysis of plasminogen activation by staphylokinase/plasminogen complex in the presence of fibrin. AB - Staphylokinase (SAK) expresses plasminogen activator activity by forming a complex with plasminogen. In order to elucidate the mechanism for the expression of enzymatic activity of the complex, a cross-linked staphylokinase/plasminogen (SAK/plg) complex was produced with disuccinimidyl suberate, and its enzymatic characteristics were compared with those of a streptokinase/plasminogen (SK/plg) complex. SAK/plg complex and SK/plg complex showed a band with a molecular weight of 110 kDa and 140 kDa by SDS-PAGE under non-reduced condition, respectively. Both complexes exhibited plasminogen activator activity in a concentration dependent manner on fibrin film and synthetic chromogenic substrate assay. The kinetic analysis of enzymatic activity of both complexes was performed. The plasminogen activator activity of SAK/plg complex was enhanced about 5-fold in the presence of FCB-2. However, SK/plg complex showed only 1.7-fold increase in the presence of FCB-2. These findings indicate that the SAK/plg complex reacts with fibrin, and efficient plasminogen activation is induced on fibrin surface. PMID- 7863468 TI - Hemostatic studies in patients with carbohydrate-deficient glycoprotein syndrome. AB - The carbohydrate deficient glycoprotein (CDG) syndrome is a newly described disorder characterized by impaired glycosylated molecules. It has been reported that transient stroke-like episodes appear in half of the patients. We performed hemostatic studies on three CDG syndrome patients belonging to two unrelated families. The most characteristic findings were decreases in antithrombin III (AT III), protein C and alpha 2 plasmin inhibitor to nearly half normal levels. Protein S was reduced in two (siblings) patients. Isoelectric focusing of AT III in native plasma revealed decreased intensity of the major band and increased intensity of a minor cathodal band. These minor AT III molecules were considered to lack an oligosaccharide sidechain. A 12-year-old girl defective not only for AT III but also protein C and protein S developed disseminated intravascular coagulation accompanied by arterial thrombosis in her left hand following dyspnea associated with bronchial asthma. These findings suggest that thrombotic predisposition in patients with CDG syndrome is due to decreased levels of major coagulation inhibitors, particularly as a result of impaired glycosylation of AT III. PMID- 7863469 TI - Ellagic acid/phospholipid-induced coagulation and dextran sulfate-induced fibrinolytic activities in beta 2-glycoprotein I-depleted plasma. AB - Beta 2-glycoprotein I (beta 2-GPI) binds negatively charged substances and inhibits intrinsic blood coagulation in the presence of ellagic acid-phospholipid suspension. Beta 2-GPI is thought to be an important protein in the reaction between negatively charged phospholipids and anti-phospholipid antibodies which appear in patients with lupus anticoagulant/antiphospholipid antibody syndrome. We prepared a monoclonal antibody against beta 2-GPI purified from human plasma and obtained beta 2-GPI-depleted plasma using a monoclonal antibody-coupled column. Either partial thromboplastin time or the activation of prekallikrein induced by diluted ellagic acid-phospholipid suspension in beta 2-GPI-depleted plasma was not different from that in control plasma. Beta 2-GPI inhibited the intrinsic blood coagulation only when added to control or beta 2-GPI-depleted plasma in excess (more than physiological concentrations). The intrinsic fibrinolysis in beta 2-GPI-depleted plasma induced by dextran sulfate was not impaired and, again, beta 2-GPI inhibited the intrinsic fibrinolysis only when added to control or beta 2-GPI-depleted plasma in excess. These results indicate that both in vitro Actin-induced intrinsic coagulation and dextran sulfate induced fibrinolytic activities are significantly inhibited by more than physiological concentrations of beta 2-GPI. PMID- 7863470 TI - Effects of alpha 2-plasmin inhibitor on plasminogen activation by staphylokinase/plasminogen complex. AB - Using a stable cross-linked SAK/plg complex, the effects of alpha 2-plasmin inhibitor on plasminogen activation by SAK were investigated. alpha 2-Plasmin inhibitor inhibited dose-dependently plasminogen activation by the SAK/plg complex. When FCB-2 or EACA was added to the reaction mixture of SAK/plg complex and alpha 2-plasmin inhibitor, the inhibitory activity of alpha 2-plasmin inhibitor was abolished and the enzymatic activity of the complexes was restored. alpha 2-Plasmin inhibitor inhibited the activity of the SK/plg complex, but neither FCB-2 nor EACA restored the plasminogen activator activity in the mixture of SK/plg complex and alpha 2-plasmin inhibitor. Using 125I-labeled SAK/plg complex or SK/plg complex, the reaction of the complex with alpha 2-plasmin inhibitor was analyzed. The SAK/plg complex produced a new complex with alpha 2 plasmin inhibitor. The formation of a new high molecular weight complex with alpha 2-plasmin inhibitor was abolished by both EACA or FCB-2. With regard to the SK/plg complex, neither EACA nor FCB-2 suppressed the complex formation with alpha 2-plasmin inhibitor. These findings indicate that the SAK/plg complex binds to fibrin, and that this complex expresses plasminogen activator activity without being affected by alpha 2-plasmin inhibitor. PMID- 7863471 TI - Factor VIII inhibitor assay using plasma F VIII versus recombinant F VIII--a comparative study. PMID- 7863472 TI - Thrombogenic properties of ultra-low-dose of acetylsalicylic acid in a vessel model of laser-induced thrombus formation. PMID- 7863473 TI - Evaluation of APC-sensitivity in normal blood donors using different reagents and instruments. PMID- 7863474 TI - No changes in PAI-1 levels after four-month n-3 PUFA ethyl ester supplementation in healthy subjects. AB - Recent studies have indicated that diets rich in fish or supplemented with fish oils may increase PAI-1 plasma levels. However, this finding has not been consistent and could be related, at least in part, to the type of supplementation. Aim of this study was to investigate the effects of medium-term treatment with n-3 polyunsaturated fatty acid (PUFA) ethyl esters on fibrinolysis. Twenty normolipemic healthy male subjects (age 27 to 41 yrs) were randomly assigned to receive either 4 x 1 g capsules of n-3 PUFA ethyl esters (ESAPENT, Farmitalia-Carlo Erba, Milan, Italy) or 4 x 1 g capsules of olive oil (as placebo) for 4 months in a double blind study. Blood samples for lipid and hemostatic studies were obtained at 0, 2, and 4 months of treatment and 1, 2 and 3 months of wash-out. Plasma lipids, fibrinolytic system, lipoprotein (a)-Lp(a)-, fibrinogen (Fbg) and prothrombin activation fragment 1+2 (F1+2) were assayed. No changes in these parameters were observed in the group of ten subjects treated with olive oil. After n-3 PUFA supplementation no significant alterations were found in plasma lipids, even if a trend to lower triglyceride and Lp(a) levels was detectable. No changes in either PAI-1 activity or PAI-1 antigen levels or F1+2 plasma levels were observed. A trend to lower Fbg levels was found after n-3 PUFA, but changes were not statistically significant. The results of this study indicate that a 4-month treatment with 4 g daily n-3 PUFA ethyl esters does not affect PAI-1 plasma levels. PMID- 7863475 TI - Fibrinolysis potentiating activity following endothelial cells-platelet interaction. AB - When porcine endothelial cells in culture are incubated in the presence of human platelets, a 90kDa neutral proteinase activity is generated on casein gel (PECAP Platelet Endothelial Cell Activated Protease). This activity was undetected when platelet extract or serum free EC conditioned medium were analysed under similar conditions. The optimum pH, isoelectric point, molecular weight and inhibitory profile of this activity were similar to Glu-plasmin. However, the low plasminogen content (less than 50ng/ml) in the conditioned medium of endothelial cells incubated with platelet could not contribute alone to this activity and the presence of a plasmin potentiating factor was suggested. This factor was separated from plasminogen by lysine-Sepharose chromatography. PMID- 7863476 TI - Fluorescence studies on plasminogen activator inhibitor 1: reactive centre cysteine mutants remain active after fluorophore attachment. AB - To investigate structural-functional aspects of plasminogen activator inhibitor 1 (PAI-1) we have taken advantage of the lack of cysteines in the PAI-1 molecule and replaced Ser344 (P3) and Asn329 (P18) with cysteine residues, thereby creating unique attachment sites for extrinsic fluorescent probes. After expression in E. coli and purification to homogeneity, both of the mutant proteins were found to have similar biochemical characteristics as wild type PAI 1 (wtPAI-1). Following labelling with 4-chloro-7-nitrobenzofurazan (NBD) and 2 (4'-iodoacetamido-anilino)naphtalene-6-sulfonic acid (IAANS) the mutant inhibitors showed similar inhibitory activities and heat stability as wtPAI-1. The purified complex between uPA and NBD-labelled P3cys mutant was found to be extremely stable, suggesting that no slow cleavage or reversible reaction occurs in complexes that have been properly formed. The rate of labelling of both mutants was decreased when the mutants were in the latent form indicating that these cysteine residues may be less accessible in the latent configuration. The PAI-1 mutants labelled with both NBD and IAANS could convert from the active to the latent form, but P3cys labelled with the larger IAANS chromophore showed a two fold decrease in the rate of conversion to latency, suggesting that a large chromophore in the P3 position may interfere with the active to latent conversion. The fluorescence spectra of the two NBD labelled mutants were similar, but the intensity was three times higher for the P3cys mutant than for P18cys. No significant spectral changes could be seen when the P3cys mutant was transferred to latency. In contrast, the P18cys mutant showed a major change in the excitation spectra characteristic of migration of the NBD chromophore from a thiol to an amine. Complex formation with uPA had no effect on the fluorescence spectrum of P18cys-NBD while the spectrum of P3cys-NBD revealed changes consistent with a restriction of the mobility of NBD probe in the uPA-PAI-1 complex. PMID- 7863477 TI - Inherited protein S deficiency: clinical manifestations and laboratory findings in 63 patients. AB - To further characterize inherited heterozygous protein S (PS) deficiencies, we studied 63 patients belonging to 33 families. Diagnosis of PS deficiency was based on protein S activity (PS Act) and/or free PS antigen (FPS Ag) levels below the lower limit of the normal range in patients not on oral anticoagulation. Depending on the level of total PS antigen (TPS Ag), two subpopulations could be distinguished: in the first one (25 patients belonging to 11 families) level of TPS Ag was reduced whereas in the second one (38 patients belonging to 22 families), TPS Ag was normal. In none of the families studied the two types of PS deficiency coexisted suggesting that they are different entities. In the 63 patients, thromboembolic events occurred in 57% of cases and were recurrent in 36.5% of patients. Age at the time of the first thrombosis ranged from 14 to 74 years, and was below 40 years in 69% of symptomatic cases. Thrombotic events were spontaneous in 64% of cases, and were associated with other risk factors in 36%. There was no apparent relationship between clinical status, symptomatic or asymptomatic, and the type or degree of the PS deficiency. Long-term anticoagulation prevented the recurrence of thrombosis in every case but one, and led to a decrease in circulating levels of C4b-binding protein suggesting the existence of a regulation between C4b-BP and PS concentrations. Together with previous reports, these findings underline the clinical and biological heterogeneity of inherited protein S deficiency. PMID- 7863478 TI - Trilinolein inhibits epinephrine-induced human platelet aggregation. AB - At concentrations ranging from 10(-9) to 10(-6) M, trilinolein inhibited epinephrine-induced platelet aggregation. This inhibition was accompanied by reduced ATP release and thromboxane B2 formation. However, concentration-response curves for the interaction between trilinolein and epinephrine showed that trilinolein was unlikely a competitive antagonist of epinephrine. Platelet aggregation induced by collagen, thrombin, ADP or arachidonic acid was not inhibited. This study supported the theory that this type of triglyceride may have therapeutic potential but the definite mechanism for its effect remains to be answered. PMID- 7863479 TI - Hemostatic abnormalities in acute myocardial infarction as detected by specific blood markers. AB - In order to elucidate the mechanism of thrombus formation in acute myocardial infarction (AMI), coagulation and fibrinolytic and inhibitory proteins were systemically examined in 12 patients with AMI and 29 normal subjects. Activities of factor XII, II and V and concentration of high molecular weight kininogen and Factor II were significantly lower in AMI patients than in normal control subjects. Factor XI activity was also increased in AMI patients as compared with normal controls. Von Willebrand Factor and fibrinogen levels were increased in patients with AMI. Plasma D-dimer concentration was also significantly higher in AMI patients than in controls. Activation of the intrinsic pathway, thrombin generation, fibrin formation and fibrin degradation may be present in patients with AMI just after the onset of coronary thrombus formation. PMID- 7863480 TI - The effect of serum amyloid protein A fragment-SAA25-76 on blood platelet aggregation. AB - The effect of the major acute phase protein serum amyloid A (SAA) on collagen induced platelet aggregation was investigated. A truncated version of SAA, SAA25 76 was tested for inhibitory capacity of collagen induced platelet aggregation in platelet-rich plasma (PRP) and whole blood (WB). The tetrapeptide RGDV, a known inhibitor of platelet aggregation, was included as a reference compound. SAA25-76 at a concentration of 390 micrograms/ml inhibited platelet aggregation induced by 1 microgram/ml of collagen in PRP. This corresponds to the plasma concentration of SAA during an acute phase response. However, the inhibitory effect of the SAA25-76 fragment was lost at higher collagen concentrations (> or = 2.0 micrograms/ml). The SAA fragment at 390 micrograms/ml had no significant effect on platelet aggregation in WB. In contrast, RGDV blocked collagen induced platelet aggregation in both PRP and WB. PMID- 7863481 TI - A phenylalanine 402 to leucine mutation is responsible for a stable inactive conformation of antithrombin. AB - In a South African family with antithrombin deficiency and unexplained thrombosis, genomic DNA analysis revealed a substitution of Phe 402 by Leu. This mutation involves an amino acid located in the carboxyterminal side of the antithrombin reactive loop and has already been observed in a French family (antithrombin Maisons-Laffitte). In both cases, the expression of the mutation is pleiotropic, i.e. results in a reduction in the circulating concentration of antithrombin and impairs both its anti-thrombin activity and its ability to bind heparin. The effect of a denaturing agent (sodium dodecyl sulfate) on the recognition of the plasma antithrombin by a polyclonal antibody was studied in an immuno-enzymatic assay. The Phe to Leu mutation decreased the sensitivity to denaturation, suggesting that the mutation increases the stability of the protein. Whether this stable conformation is due to a partial insertion of the amino-terminal side of the reactive loop, which would explain how both protease binding and heparin binding are affected, remains to be determined. PMID- 7863482 TI - [Veterinary dentistry (8) Extraction of dental elements in cats]. AB - This review gives indications for tooth extraction in cats as well as a brief description of the necessary instrumentation. General guidelines and a step-by step procedure for an extraction lege artis are described. PMID- 7863483 TI - [Intravenous administration of Ivomec in horses]. AB - Now and then cases have been reported where horses died suddenly after intravenous application of Ivomec. Lethal anaphylactic reactions in horses are known to occur incidentially after intravenous application of drug dissolved in propyleneglycol or glycerolformol. Since Ivomec is registered for use in cattle, sheep and pig, its use in horses has to be regarded as 'off label use'. It is concluded that in the treatment of inhibited stages of cyathostomes ivermectin has no effect whether or not it is applied intravenously or orally. Since lethal anaphylactic reactions can occur, intravenous application of Ivomec can not be justified for 'off label use'. PMID- 7863484 TI - [Demonstration project stimulates welfare of domestic animals]. AB - The Ministry of Agriculture, Nature Management and Fisheries has a policy of stimulating the well-being of animals. This policy has led to the so-called Animal-friendly Housing Systems Demonstration Project. Various housing systems are demonstrated in full function on a number of farms (ca 90). The Demonstration Project highlights aviary systems for laying hens, a container transportation system for broilers, the housing of sows in groups, free-range systems for sow and fatteners and a strawflow system for fatteners. For beef bulls the farms show how group housing can be combined with rubber covered slatted floors or littered cubicles. For veal calves the farms show group housing combined with rubber covered slatted floors, more space per animal and or feeding of roughage. For female followers these are laying areas covered with straw. Brochures on the various systems are available in the Dutch language. PMID- 7863485 TI - [What is a double-angled heel?]. PMID- 7863486 TI - Risk factors in coronary artery bypass surgery for patients 40 years of age and younger. AB - In patients undergoing coronary artery bypass surgery while under 40 years of age, prevalence of risk factors for coronary artery disease and prognostic factors for mortality were assessed. Ninety-four patients of such age were operated from 1979 until 1989. Eighty-two patients were male, 12 female. Fifty eight patients (62%) had a history of myocardial infarction. Patients were predominantly in New York Heart Association class II or III (69%). In this study prevalence of risk factors for coronary artery disease was different compared to studies of patients undergoing coronary artery bypass grafting over 40 years of age. Smoking (83%), hypercholesterolaemia (79%), and positive family history for coronary heart disease (66%) were more prevalent in this study compared to other studies concerning patients older than 40 years of age whereas the occurrence of hypertension (25%) and diabetes (6%) was lower. Six patients (6%) had one-vessel disease, 15 patients (17%) had two-vessel disease and 73 patients (78%) showed triple-vessel disease. Similar studies of patients older than 40 years of age showed a lower prevalence of triple vessel disease than in this study. Hospital mortality amounted to 3 patients (3%). Five-year-survival rate was 93%. Multivariate survival analysis revealed left main stenosis and concomitant operations as significant prognostic factors of survival. Number of vessels diseased, sex, priority of operation, reoperation, or impaired left-ventricular function were not prognostic factors for mortality in this study. PMID- 7863487 TI - In-vitro effects of cardioplegic solutions on human saphenous vein endothelium--a scanning electron microscopy study. AB - In order to evaluate the effects of potassium cristalloid cardioplegic solutions (CPS) on the endothelial morphology, human saphenous veins were studied by scanning electron microscopy after exposure to three CPS named MKP (magnesium potassium-procaine cardioplegia), LK (low-potassium cardioplegia), and HKA (high potassium-albumin cardioplegia) and to their main components. Vein rings, selected from the saphenous veins sampled for graft harvesting in 63 patients undergoing aorto-coronary bypass surgery, were exposed for 30, 60, and 120 minutes to the following buffered solutions: Krebs bicarbonate (as control); MKP cardioplegia; KCl (16.0 mmol/L); MgCl2(2).6H2O (16.0 mmol/L); Procaine (0.05 mmol/L); NaCl (92.5 mmol/L); LK cardioplegia; KCl (10.0 mmol/L); Mannitol (74.3 mmol/L); Glucose (27.7 mmol/L); HKA cardioplegia; KCl (30 mmol/L). Severe endothelial lesions, consisting of diffuse disendothelialization and diffuse signs of endothelial suffering, were induced by KCl (30 and 16 mmol/L) after 60 120 min, and by MKP cardioplegia and KCl (10 mmol/L) after 120 min. Moderate endothelial lesions, characterised by diffuse endothelial surface changes and focal cellular loss, were induced by KCl (30 and 16 mmol/L) after 30 min, MKP cardioplegia and KCl (10 mmol) 30-60 min, LK cardioplegia, HKA cardioplegia, and MgCl2.6H2O after 120 min. Slight endothelial lesions, consisting of diffuse endothelial bulging, or absence of significant endothelial changes, were found in samples otherwise treated. Our findings showed a significant damaging effect of CPS on the human saphenous vein endothelium in-vitro. The endothelial lesions seemed related to the presence of potassium and magnesium, and to prolongation of the time of exposure to the cardioplegic solutions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863488 TI - A novel anti-oxidative agent improves recovery of the heart after cardiac arrest. AB - Experiments were designed to determine whether adding a synthetic anti-oxidative agent H 290/51 (cis-7methyl-9-methoxy-5,5 a,6,10 b-tetrahydroindeno [2,1-b] indole), to a crystalloid cardioplegic solution was beneficial for myocardial recovery and coronary reactivity in isolated rat hearts after six hours cold arrest. Two groups of hearts were single-flush perfused using the Langendorff technique (10 ml at 4 degrees C) with either Plegisol (St. Thomas' Hospital Solution) (n = 6) or Plegisol with H 290/51 (n = 6) added to a final concentration of 1 mummol/L. The heart were then stored for six hours in the respective solution at 4 degrees C. A third group of hearts (n = 6) were single flush with Plegisol and reperfusion was immediately started (the 'non-stored' group). Before and after the arrest phase the hearts were perfused at constant pressure with Krebs-Henseleit bicarbonate buffer. To evaluate coronary vascular function, endothelium-dependent vasodilatation was induced with 5-hydroxy tryptamine (5-HT) and smooth-muscle relaxation with nitroglycerin (GTN). Myocardial contractility after 30 min reperfusion, measured as left-ventricular developed pressure (LVDP), was significantly improved in hearts in the Plegisol+H 290/51 group compared to hearts in the Plegisol group (LVDP 89 +/- 8.5% vs 57.2 +/- 10.7% of prearrest values; p < 0.05). LVDP in hearts receiving Plegisol+H 290/51 was comparable to non-stored hearts (88.2 +/- 1.3%). The vasodilatory response to GTN was significantly reduced in hearts perfused with plain Plegisol (p < 0.05) but not in hearts receiving Plegisol+H 290/51 or in the non-stored hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863489 TI - The protective effects of high-dose ascorbic acid on myocardium against reperfusion injury during and after cardiopulmonary bypass. AB - The protective effects of high-dose ascorbic acid (250 mg/kg) on the myocardium were observed in 85 patients undergoing Cardiopulmonary Bypass (CPB). The changes in serum Malonyldialdehyde (MDA). Creatine Phosphokinase (CPK), Creatine Phosphokinase isozyme (CPK-MB) and Lactic Dehydrogenase (LDH) in group B (n = 45, receiving ascorbic acid) were lower (p < 0.05) than in group A (n = 40, no ascorbic acid) during and after CPB. The MDA remained at a higher level two days postoperatively; CPK and CPK-MB, the sensitive and specific reflectors of myocardial injury, recovered very slowly in the control group (A) after the operation. The hearts in all the patients of group B resuscitated automatically intraoperatively while five cases (12.5%) needed defibrillation in group A. The cardiac index (CI) measured in ICU in group B was higher than in group A (p < 0.05). The patients needed shorter ICU and hospital stays in group B than in group A. The results indicate that ascorbic acid can act as a scavenger of free radicals to decrease the peroxidation of the lipids present in the cell membrane and remove the radicals to protect the myocardium from ischemia-reperfusion injury effectively during and after open-heart operation. PMID- 7863490 TI - Surgical treatment of aneurysms of the aortic arch using a simplified selective cerebral perfusion technique. AB - Between April 1989 and October 1993, 35 patients underwent aortic arch reconstruction for aneurysms using cardiopulmonary bypass (CPB) with selective cerebral perfusion (SCP). Of the 35 patients, the initial 19 (Group P) consecutively received simplified SCP (partial brachiocephalic perfusion; PBP), and the next 16 (Group S) were consecutively treated with standard SCP. For cerebral protection, blood was supplied to the right axillary artery in Group P, and to the right axillary and the left common carotid arteries in Group S. The aneurysms was aortic dissection in 24 patients, and was secondary to arteriosclerosis in the remaining 11. Partial replacement of the aortic arch together with the ascending aorta was the most commonly performed procedure in both groups. The cardiopulmonary bypass time and the cardiac arrest time were not significantly different between the two groups. The overall cerebral perfusion time was significantly longer in Group S (100 min) than in Group P (65 min); however, when 2 patients with an accidental prolongation of the cerebral perfusion time in Group S were excluded, there was no significant difference in the cerebral perfusion time between the two groups. Early death occurred in 3 patients (15.8%) in Group P, and 2 patients (12.5%) in Group S, however, there were no deaths related to the selective cerebral perfusion technique, and there were no late deaths in either group. Cerebral complications were seen in 1 patient in each group (6.3% vs. 6.7%, not significant). These results suggest that the simplified SCP (PBP) under hypothermic CPB provides as satisfactory cerebral protection as standard SCP, so long as the patency of the circle of Willis is confirmed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863491 TI - Diagnostic value of dobutamine stress echocardiography in coronary artery disease. AB - In order to assess the value of dobutamine stress echocardiography (DSE) for detecting coronary artery disease (CAD), 67 consecutive patients (mean age +/- SD was 58 +/- 8 years, range 35 to 75; 46 men and 21 women) with known or suspected CAD undergoing selective coronary angiography within the week following the DSE were studied. Two patients were excluded from the study because of insufficient echocardiographic imaging. Dobutamine (5 to 30 micrograms/kg/min by 5 micrograms/kg/min increments) was infused in 5-minute intervals. All the patients had 12-lead electrocardiogram (ECG) recorded at rest and at each stage of dobutamine infusion. There was significant CAD (> or = 50% diameter stenosis) in 42 patients (64.6%) with 16 patients having 1-vessel, 7 patients having 2-vessel and 19 patients having 3-vessel CAD. In 22 patients coronary angiogram was normal. DSE was positive in 33 of 42 patients with CAD. The test was negative in 20 of 23 patients without CAD. Compared with coronary angiography, the overall sensitivity of DSE for detecting CAD was 78.6% specificity 87%, positive predictive value 91.7%, negative predictive value 69%, and accuracy 81.5%. The sensitivity in those with one-vessel, two-vessel, three-vessel and multivessel disease was 62.5%, 85.7%, 94.7%, and 92.3% respectively. DSE was well tolerated in all patients. The study was not prematurely terminated due to a side effect in any patient. This study indicated that DSE is a practical method for the non invasive assessment of significant CAD, for determining the patients who require invasive tests, and for predicting the extent of disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863492 TI - Ultrastructural studies of acute rejection following single lung transplantation in the rat--histological and immunohistological findings. AB - Nowadays the acute and especially chronic lung rejection are the major problems after lung transplantation (L-Tx) with relevant influence on longterm survival. We performed lung transplantation in rats to study a possible role of ultrastructural lesions in the graft during the acute rejection process, concerning their reversibility/irreversibility and influence of the chronic rejection. Based on histologic and immunohistologic studies after L-Tx in MHC different and strong reactive rat strain combination AVN-LEW and filial generation (AVN-LEW)F1-LEW (n = 57 and n = 32) electronmicroscopic studies (TEM, SEM) were performed in the combination AVN-LW (n = 20) on postoperative day 0, 1, 2 and 5, all without immunsuppressive therapy. Syngenic grafts (LEW-LEW; n = 12) served as controls. Histologically the allografts were classed according to the proven acute rejection phases latent, vascular, alveolar and destructive. The immunhistological and electronmicroscopic results correlated with these rejection phases. There was no difference between the rat strain combinations. All allografts developed acute rejection on postoperative day 2 and were destroyed on postoperative day 5/6. Initially T-helper-cells, later cytotoxic-T-cells and macrophages played the predominent role in the acute rejection process. In the ultrastructural specimens alterations of the blood vessels, pneumocytes type-II, and surfactant gave more information. Initially flattening of endothelial cells and circumscribed lesions of graft vessels occur, increasing in the allografts up to extensive vascular wall destructions, accompanied by total thrombotic occlusion. Disturbances of surfactant production observed in the grafts of all strain combinations are not homogenous.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863493 TI - Squamous cell carcinoma of the lung: does the nm23 gene expression correlate to the tumor stage? AB - We examined the nm23 gene activity in 30 human squamous cell carcinomas of the lung using the Northern blot analysis. Matched healthy lung tissue was available from 10 patients. 26 tumor samples were obtained after resection treatment between 1986 and 1990, 4 additional samples of advanced stages from autopsy. We found a significant increase of nm23 expression towards advanced stages of squamous cell carcinoma (IIIa vs. I: p < 0.015, IV vs. II: p < 0.043, IV vs. I: p < 0.043). Furthermore in stage I and II, poorly differentiated squamous cell carcinomas contained significantly more nm23 mRNA than did moderately differentiated ones (p < 0.027). We could also demonstrate an inverse correlation between the levels of nm23 mRNA and disease-free survival after resection treatment (p < 0.016, chi 2-test for trend). Thus the nm23-gene activity correlates to the tumor stage and the grade of differentiation of the squamous cell carcinoma of the lung, and is therefore of prognostic relevance. It might be possible to describe the biological behaviour of the individual tumor more accurately by the additional measurement of the nm23 mRNA. PMID- 7863494 TI - Staged replacement of the canine trachea with ringed polyethylene terephthalate grafts. AB - The reconstruction of extensive defects of the trachea ist best accomplished by the use of the patient's own tissue. Unfortunately, this is not always feasible and several prosthetic devices for replacement of the trachea have been described. In an experimental study staged tracheal replacements were performed in five dogs using a ringed polyethylene terephthalate (PET) tubular prosthesis previously cultured in the major omentum of the subjects. A set of stainless steel arches embodied in silicone compound was designed to prevent collapse of the prosthesis. One of the subjects died on the 10th post-operative day of an unidentified cause and the remaining four eventually developed signs of respiratory distress. The cause of the respiratory insufficiency was anastomotic stenosis in every case. Infection, erosion, collapse or displacement were not observed. The rings designed to avoid collapse of the prosthesis represent a suitable alternative for use as external reinforcement in the tracheal situation. The PET grafts implanted as tracheal prosthesis according to the guidelines of this protocol consistently developed anastomotic stenosis and failed to support a functional respiratory epithelium. A further conclusion is that the use of absorbable sutures encourages anastomotic dehiscence and thus must be avoided. PMID- 7863495 TI - Fibrin-glue-coated collagen fleece in lung surgery--experimental comparison with infrared coagulation and clinical experience. AB - Diffuse parenchymal bleeding and major air leaks still present a challenge to the thoracic surgeon. This study was therefore designed to evaluate efficacy and handling of fibrin-glue-coated collagen fleece, to address these problems. In an experimental part defects were produced in lungs of troll pigs to compare the use of the fleece with infrared coagulation. Immediate airtightness and postoperative adhesions were evaluated. Scores were designed to evaluate quality and extension of the adhesions. In a clinical study parenchymal resection sites were sealed with fibrin-glue-coated collagen fleece in 52 patients. No patient suffered from postoperative bleeding. In three cases air leaks were still present on the third postoperative day, representing a 5.8% failure rate. 92.3% of the patients showed neither postoperative hemorrhage nor prolonged air leaks. A fixed combination of collagen fleece and fibrin glue consequently can be considered as a valuable tool in thoracic surgery. PMID- 7863496 TI - The non-functioning pleuro-peritoneal shunt: revise or replace? AB - Pleural malignancy commonly leads to troublesome and recurrent effusion. Cure is not possible and effective palliation is important for the 2-3 months median survival following diagnosis. We have previously emphasised the role of pleuro peritoneal shunts (PPS) in this situation. A number of shunts (11%) malfunction and we have revised our policy as to how best to deal with this problem. We studied our 70 patients who required the insertion of 71 PPS over seven years: there were 8 cases (11%) of non-functioning shunts necessitating re-exploration. In two cases the shunt was blocked due to infection which may have been present prior to insertion of the shunt. In these cases the shunt was removed and drainage was performed. In one shunt non-function was due to obstruction of the pleural limb and it was re-positioned successfully. The remaining five shunts were found to be blocked by fibrinous tissue. Replacement of two of these led to a functioning shunt until the death of the patients, while the three shunts which were revised failed to function. One shunt became infected and was removed and the other two became blocked again. Following subsequent replacement the function was restored until the death of the two patients. We conclude that non functioning pleuro-peritoneal shunts should be replaced rather than revised to avoid subsequent complications. PMID- 7863497 TI - A simple surgical atrial septectomy for complex congenital heart disease. AB - A simple method of surgical atrial septectomy using a rongeur (Kerrison bone cutting forceps), which is used in neurosurgery, is described. The closed rongeur is inserted into the left atrium through the right atrial appendage and the atrial septum. Then it is opened and the edge of the atrial septal defect and/or patent foramen ovale can be hooked by pulling slowly. The rongeur is then tightly closed again and pulled out together with the resected atrial specimen. This technique is safer and simpler than the Blalock-Hanlon technique or atrial septectomy with extra-corporeal circulation for older infants in whom balloon atrial septostomy is difficult. PMID- 7863498 TI - Subaortic blind mitral pouch in a double-inlet right ventricle. AB - A full-term baby girl was diagnosed at birth using echocardiography to have a single ventricle with common atrioventricular valve and subaortic ridge. On the 22nd day after birth she was admitted to hospital for intensive care after sudden onset of cyanosis. Three days later she died after repeated attacks of bradycardia. At necropsy the heart was examined by sequential segmental approach. Situs solitus with double-inlet right ventricle and ventriculoarterial discordance was revealed. The left atrial floor was separated from the ventricle by a small hole leading to a translucent blind pouch, which bulged toward the subaortic outflow tract with its hypoplastic tensor apparatus connected to the subaortic infundibulum. The aortic valve was normal. The pulmonary trunk with a competent bicuspid valve arose from the left-sided rudimentary left ventricle. The pulmonary blood flow was limited by a slit-like interventricular communication. Obstruction of the pulmonary venous return due to the natural closing of the patent foramen ovale and the mitral atresia led to her premature death. PMID- 7863499 TI - Intraperitoneal administration of nucleoside-nucleotide mixture inhibits endotoxin-induced bacterial translocation in protein-deficient mice. AB - Nucleosides and nucleotides as a precursor for nucleic acid synthesis may be essential for rapidly growing cells, since intestinal epithelial cells have limited capacity for the de novo purine and pyrimidine synthesis. The present study was undertaken to determine the effect of intraperitoneal administration of nucleoside-nucleotide mixture (NNM) or saline on endotoxin-induced bacterial translocation, ileal histology, and cecal population levels in protein-deficient mice. Intraperitoneal administration of NNM for 14 days was associated with reduced translocation of gram-negative enterics to the mesenteric lymph node and spleen in comparison to saline. Histologically, the extent of the damage to the gut mucosa was greater in the saline group. This was confirmed by the profound diminution of the villous height, crypt depth, and the intestinal wall in the saline treated group as compared to the NNM treated group, suggestive of the efficacy of NNM in improving the gut and epithelial mucosal cells. However, the cecal population levels in both groups were not different. Additionally, the mice in the saline group were more susceptible to the lethal effects of endotoxin as compared to the NNM group suggesting that NNM may be essential for the enhancement of the host defense system. These results suggest that NNM may be used to an advantage to inhibit or reduce the incidence of endotoxin-induced bacterial translocation and improved survival in protein-deficient mice. PMID- 7863500 TI - Human cytomegalovirus neutralizing antibody response in Japanese children with bone marrow transplantation. AB - Thirty-two children with bone marrow transplantation (BMT) received intravenous injections of gammaglobulin (IVIG) with a high titer of neutralizing (NT) antibody against human cytomegalovirus (HCMV) (200 mg/kg/week) from 1 week before to 4 months after transplantation. NT antibody titers before BMT and the highest levels in serial determinations conducted after BMT were compared for each patient. They were classified into three groups according to the antibody response: primary HCMV infection as group I, endogenous reactivation or external reinfection as group II, and indeterminable cases as group III. Two (6.3%) out of 32 patients examined had BMT-associated primary HCMV infections, but did not show any clinical symptoms. Significant changes in clinical parameters were also lacking in all the other 30 patients, independent of whether they shed viruses into the urine, or demonstrated on antibody boost. It was concluded from the group variation that the antibody response was indeed due to the engraftment of BMT, rather than to a direct effect of treatment with IVIG. Our results further indicate that passive immunization with HCMV antibody does not prevent infection, but confers some protection against symptomatic disease. PMID- 7863501 TI - Binding of metallothionein to rat spermatozoa. AB - Binding studies of metallothionein and rat spermatozoa were performed using 125I Tyr-metallothionein (125I-MT). Reactions between 125I-MT and spermatozoa indicated that MT bound in two forms, namely, middle affinity (Kd1 = 2 x 10(-9) M) binding and low affinity (Kd2 = 1 x 10(-8) M) binding. Labeled MT binding to spermatozoa was inhibited by adding anti-MT antibody. Total binding reactions of MT were temperature and incubation time dependent. By transmission electron microscopy using a gold conjugate (indirect method), gold particles bound to MT were shown to bind to the cell membrane of the head and the proximal portion of the tail. By optical autoradiography, grains of labeled MT were localized mainly in the head and the proximal portion of the tail. By electron microscopical autoradiography, grains of labeled MT were identified mainly in the cell membrane of the head and tail and partly in the nucleus. These results suggest that MT has both specific and non-specific binding sites on the spermatozoal membrane. PMID- 7863502 TI - The effect of an SOD derivative (SM-SOD) administration in a burned rat model. AB - To determine whether superoxide radicals may influence the pathogenesis of burn injury, we investigated the effects of a long-acting, site-directed superoxide dismutase derivative (SM-SOD) on the rats subjected to burn shock. Anesthesized animals were injected intravenously with either 2 ml/kg of saline or SM-SOD (10 mg/kg; dissolved in saline). After 30 min they were subjected to full-thickness burns of about 40% of total body surface area. The 7-day survival rate was significantly higher in the SM-SOD-treated animals than in the untreated controls. Also, administration of SM-SOD markedly inhibited the increase in the levels of thiobarbituric acid reactive metabolites, such as lipid peroxides in the plasma, lung and kidney, and the decrease in plasma protein levels particularly at the early stage of burn injury. These findings suggested that superoxide radicals may play a critical role in the pathogenesis following thermal injury. PMID- 7863503 TI - Late results after correction of ventricular septal defect with severe pulmonary hypertension. AB - Fifty-eight patients with ventricular septal defect (VSD) associated with severe pulmonary hypertension (Pp/Ps > or = 0.90) were repaired between 1971 and 1992. Their preoperative Pp/Ps, Rp/Rs and Rp were 0.98 +/- 0.06, 2.37 +/- 1.20 and 4.81 +/- 3.06 units.m2, respectively. Late results were analyzed in 56 operative survivors. The age at the time of operation ranged from 2 months to 32 years (average 4.1 years) and the postoperative follow-up period ranged from 1 month to 20 years (average 5.5 years). Eighty-two percent of the patients were in New York Heart Association functional class I, 15% were in class II and 3% in class III. The postoperative Pp/Ps and Rp/Rs significantly decreased to 0.41 +/- 0.13 (p < 0.001) and 0.25 +/- 0.16 (p < 0.001), respectively. There were significant differences in Rp/Rs and Rp between the patients operated on before (Group 1) and after 2 years of age (Group 2). Rp/Rs and Rp in Group 1 were 0.17 +/- 0.06 and 2.52 +/- 0.65 units.m2, whereas 0.31 +/- 0.19 (p < 0.05) and 4.26 +/- 1.88 units.m2 (p < 0.05) in Group 2, respectively. One patient died 14 months after VSD closure due to respiratory failure. It is concluded that a patient with VSD associated with severe but reversible pulmonary hypertension should be surgically corrected before 2 years of age. PMID- 7863504 TI - Diabetic retinopathy in Japanese patients with long-standing pancreatic diabetes due to calcifying pancreatitis. AB - This study analyzed the prevalence, aggravating factors (including duration of diabetes, glycemic control, body mass index, hypertension, serum total cholesterol, changes of ST on ECG and diabetic therapies) and characteristics of diabetic retinopathy in 75 patients with pancreatic diabetes resulting from calcifying pancreatitis. The patients were divided into three Groups: Group I (27 patients in whom diabetes was detected earlier than pancreatic stones), Group II (36 patients in whom diabetes and pancreatic stones were simultaneously detected) and Group III (12 patients in whom pancreatic stones were detected earlier than diabetes). The prevalence of retinopathy was dependent on the duration of diabetes as well as poor glycemic control. It was significantly (p < 0.01) higher among the patient with the duration of diabetes that was more than 5 years than that of the patients whose duration was less than 5 years. The prevalence of retinopathy in Group I (63%) was significantly (p < 0.05) higher than that in Group II (30.6%) and Group III (12.5%). Proliferative retinopathy was not found in any patients with a duration of diabetes less than 5 years, while it was found in 5 patients with a duration of more than 5 years (5 cases out of 31 patients). Diabetic retinopathy was correlated with the duration of diabetes and glycemic control, and was not linked to frequency of hypoglycemia and family history of diabetes. From the results above, we concluded that diabetic retinopathy in patients with pancreatic diabetes due to calcifying pancreatitis might be taken as evidence that such complications are primarily due to chronic hyperglycemia and the duration of diabetes mellitus rather than to genetic factors and other factors (body mass index, hypertension, serum total cholesterol and diabetic therapies). PMID- 7863505 TI - Differences in immune responses to tumor induced in syngeneic hosts by injection of hybrid and parental tumor cells. AB - Immunization of C3H/He mice with L-FM3A#2 hybrid cells, made by fusion of ascitic mammary carcinoma FM3A#2 cells with 8-azaguanine resistant LAG cells, both of C3H/He mouse origin, resulted in spleen T cell-dependent resistance to the parental FM3A/R cells. These spleen T cells, purified by passing through a nylon fiber column, could be demonstrated to have Thy-1.2 and Lyt-2.1 antigens, and not L3/T4 antigens. After immunizing with irradiated FM3A/R cells, cytotoxic cells other than cytotoxic T lymphocytes (CTL) appeared, these presumably being nonphagocytic macrophages or polymorphonuclear cells. In this case, anti MM antiserum was generated at an earlier stage than when mice were immunized with the L-FM3A#2 cells. The cytotoxic mechanism is discussed as to the significance of the surface antigen. PMID- 7863506 TI - Unrestricted T cell-mediated cytotoxicity to major histocompatibility antigen generated with tumor hybrid cells. AB - Splenic T cells from C3H/He mice injected with the LFM3A#2 hybrid cells intraperitoneally (i.p.) showed cytotoxic activity against the parental FM3A/R tumor cells. We studied the target antigens recognized by cytotoxic T cells (CTL) and the following results were obtained. 1) CTL specifically recognized the MM antigens on the surface of target cells in effector phase. 2) The H-2K or H-2D antigens were not involved in T cell effector function. PMID- 7863507 TI - Inhibition of human acetylcholinesterase by cyclophosphamide. AB - The inhibitory effect of cyclophosphamide (CP) on human erythrocyte membrane bound acetylcholinesterase (AChE) was investigated in the present study. It was found that CP inhibits the AChE reversibly with an IC50 of 511 microM. The Michaelis-Menten constant (Km) was 132 microM for AChE in the control system; a value increased by 78% in the CP treated system. The Vmax was 73.8 mumol/h/mg protein for the control system. The Lineweaver-Burk plot and Dixon plot indicated that the nature of this inhibition is of the linear mixed type, i.e., partially competitive and purely noncompetitive. The values of Ki and KI were estimated as 378 and 582 microM, respectively. The KI was greater than Ki indicating that noncompetitive inhibition was predominant over competitive. PMID- 7863508 TI - Demonstration of chlorobenzene-induced DNA damage in mouse lymphocytes using the single cell gel electrophoresis assay. AB - The DNA damaging effect of chlorobenzene was investigated in peripheral lymphocytes and bone marrow cells from C57BL/6 female mice using a gel electrophoresis assay for DNA from single cells ('the single cell gel electrophoresis assay') under alkaline conditions. The effect of chlorobenzene was studied both after single and repeated intraperitoneal injections of 750 mg/kg body weight. The cytostatic agent cyclophosphamide (150 mg/kg, i.p.) was used as a reference substance, and vehicle-treated mice as controls. DNA damage was recorded 16 h after the (last) injection, using an automated computerized image analysis system specifically designed for the single cell gel electrophoresis assay. There was evidence of chlorobenzene-induced DNA damage after 3 days of repeated exposure in peripheral lymphocytes, but no indications of such an effect in bone marrow cells. Cyclophosphamide induced significant damage to DNA both in bone marrow cells and lymphocytes, the effect being most pronounced in the latter cells. It is concluded that high-dose exposure to chlorobenzene is associated with genotoxicity to peripheral lymphocytes. However, this solvent is apparently not a major hazard to bone marrow cells, even after repeated high-dose exposure. PMID- 7863509 TI - Agglutinating activity of wheat gliadin peptide fractions in coeliac disease. AB - The K 562 (S) cell agglutinating activity of peptides obtained from in vitro digestion of bread wheat gliadins has been shown to be associated with a small fraction (coded as Fraction C), that can be easily separated by affinity chromatography of the whole digest on a sepharose 6-B-mannan or sepharose 6-B oligomers of N-acetyl-glucosamine. Although the whole gliadin digests from 12 durum wheat varieties were unable to agglutinate K 562 (S) cells, all these digests were found to contain an active Fraction C. The lack of agglutinating activity of the whole durum wheat gliadin digests has been shown to be associated with the presence in these digests of another peptide fraction (coded as Fraction B) that is eluted much earlier from the sepharose 6-B-mannan column and is able to inhibit the cell agglutinating activity of Fraction C. Such an active Fraction B is not present in bread wheat gliadin peptides, although peptides with the same elution profile as Fraction B have been detected. PMID- 7863510 TI - A two-centre study for the evaluation and validation of an animal model for the assessment of the potential of small molecular weight chemicals to cause respiratory allergy. AB - This study evaluated a single intradermal injection model in the guinea pig with subsequent inhalation challenge and serological analysis as a method to predict the potential of chemicals to induce respiratory allergy. Four known respiratory allergens (trimellitic anhydride, diphenyl methane diisocyanate, phthalic anhydride and toluene diisocyanate (TDI)) were screened by two industrial research laboratories using this protocol. Dinitrochlorobenzene, a potent contact allergen, was included as a negative control material. In both laboratories, the respiratory allergens, but not the contact allergen, induced high titre antigen specific antibodies in treated animals. The inhalation challenge results were similar in both laboratories but were less conclusive in that exposure to free TDI failed to induce pulmonary responses, probably because it fails to penetrate to the deep lung in sufficient concentration. Although the assay shows promise as a means of identifying chemical respiratory sensitisers, its use as a routine screen for the prediction of the ability of materials to induce respiratory allergy in man is probably questionable. PMID- 7863511 TI - In vitro correlates of the acute toxic syndrome induced by some monoclonal antibodies: a rationale for the design of predictive tests. PMID- 7863512 TI - Selective modulation of immune function resulting from in vitro exposure to methylenedioxymethamphetamine (Ecstasy). AB - Abuse of illicit analogs of methamphetamine (i.e., 'designer drugs') represents a growing problem. One of the most popular methamphetamine analogs is (+/-)-3,4 methylenedioxymethamphetamine (MDMA), commonly known as Ecstasy. The authors demonstrated previously that in vitro exposure to methamphetamine results in modulation of immune functional parameters necessary for host defense. The current study was performed to assess the potential direct (in vitro) immunomodulatory effect of exposure to a modified methamphetamine. Splenocytes or peritoneal macrophages from B6C3F1 mice were cultured in vitro at MDMA concentrations of 0.0001-100 microM. T-cell regulatory function was assessed by anti-CD3-mediated production of IL-2 and IL-4, B-cell function was assessed by quantitating cellular proliferation, natural immunity was assessed by quantitating natural killer (NK) cell activity, T-cell effector function was evaluated as a function of cytotoxic T-lymphocyte (CTL) activity, and macrophage function was assessed by IL-6 tumor necrosis factor (TNF) production. In vitro exposure to MDMA had no effect on B-cell proliferation at any concentration tested. In comparison, in the absence of direct cellular toxicity, production of IL-2 was enhanced at concentrations as low as 0.0001 microM. IL-4 production was not affected by exposure to any concentration of MDMA examined, suggesting a differential alteration in T-helper cell function by this compound. Basal and augmented NK cell function were enhanced at MDMA concentrations between 0.0001 and 1.0 microM when examined at an effector:target ratio of 100:1. CTL induction was significantly suppressed at a concentration of 100 microM. Finally, macrophage production of TNF was slightly suppressed at 10 and 100 microM MDMA, although this inhibition was not statistically significant. PMID- 7863513 TI - Cytotoxicity of NO2 gas to cultured human and murine cells in an inverted monolayer exposure system. AB - We report the development of an optimised exposure system for the exposure of inverted cell cultures to NO2, which presents several advantages over conventional, right-side-up exposure systems. Firstly, the cells may be directly exposed to NO2 in the gas phase for up to 1 h, without the interposition of an aqueous layer. Secondly, the chamber system allows simple and precise control of the gas concentration during the exposure. Finally, the system allows the simultaneous exposure of large numbers of cells under sterile conditions, facilitating further culture of the cells after the exposure period. We report the application of this system to a comparative study of the toxicity of NO2 in three different cell types involved in the circuit of the inflammatory response, the IC-21 murine macrophage line, the A-549 human pulmonary type II-like epithelial cell line and human umbilical vein endothelial cells. As little as 2 ppm NO2 for 20 min reduced colony-forming efficiency of HUVE cells and A-549 cells and A-549 cells to 35% and 78% of their air controls, respectively. Exposure to 5 ppm NO2 for 1 h increased lactate dehydrogenase release of HUVE cells, IC-21 macrophages and A-549 cells from 7.9% to 21.6%, 5.7% to 10.9% and 2.0% to 3.4%, respectively, whilst 10 ppm NO2 for 1 h lowered cellular glutathione in HUVE cells, IC-21 cells and A-549 cells from 35.2 nmol/mg to 23.3 nmol/mg, from 45.0 nmol/mg to 31.0 nmol/mg and from 86.4 nmol/mg to 69.2 nmol/mg, respectively. Of the cell types tested it was shown that HUVE cells and IC-21 cells were equally sensitive to the toxicity of NO2, whilst A-549 cells displayed considerable resistance, perhaps due to the considerably higher levels of glutathione in this cell line. Further, a comparison of the sensitivity of HUVE cells to NO2, using several modes of exposure (inverted and right-side-up (either rocked or static)) and the assay of lactate dehydrogenase and [3H]deoxyglucose release, revealed that the present inverted exposure technique potentiated the acute cytotoxicity of the gas. PMID- 7863514 TI - An overview of the electronic health and safety services of the Canadian Centre for Occupational Health and Safety. AB - This article describes the electronic information services of the Canadian Centre for Occupational Health and Safety (CCOHS). The aim of CCOHS is to promote a healthier and safer workplace. CCOHS' key ways of achieving this are its CD-ROM (compact disc read-only memory) service, CCINFOdisc, and its on-line computer network called, CCINFOline. CCOHS' electronic services contain some 50 databases with bibliographic and factual information from CCOHS and major organizations in other countries, such as NIOSH (National Institute for Occupational Safety and Health) in the U.S., the International Occupational Safety and Health Information Centre (CIS) in Switzerland, and the Institut National de Recherche et de Securite (INRS) in France. In addition, the CD-ROM service includes The Chemical Advisor disc of regulatory and advisory lists for chemicals from the U.S. and other countries; full-text discs, such as CANADIAN HEALTH AND SAFETY LEGISLATION and two interactive, multimedia education and training products on the safe use of chemicals, and on preventing repetitive motion injuries. These services, available at an affordable price, are delivered worldwide and currently have thousands of organizations as subscribers in about 50 countries. Founded by the Government of Canada in 1978, CCOHS is the national resource in occupational health and safety information. In addition to the electronic service, other services offered are an inquiry service, which is free in Canada, and a publications service. PMID- 7863515 TI - Fatty acid conjugates of xenobiotics. AB - In this review, we discuss the formation and toxicity of fatty acid conjugates of xenobiotics. Conjugates formed in vivo and in vitro and those detected as contaminants are reviewed. Due to the lipophilic nature of these conjugates, they may accumulate in various body organs and cause toxic manifestations. In vivo formation of these fatty acid conjugates appears to be catalyzed by enzyme(s). Fatty acid ethyl esters are the most widely studied esters and have been implicated in the onset or pathogenesis of myocardial and pancreatic diseases in alcoholics. In experimental animals, studies on 2-chloroethyl linoleate, palmitoylpentachlorophenol and oleoyl and linoleoyl anilides clearly indicate that lipid conjugates of xenobiotics are involved in target organ toxicity. These findings warrant further detailed studies to isolate and identify other fatty acid conjugates and to evaluate their toxicity. Thorough toxicokinetic and metabolic studies are also needed to identify putative toxic agents. Identifying these agents could help in understanding the mechanism of pathogenesis associated with lipid conjugation. Finally fatty acid conjugates of drugs (prodrugs), have been shown to have increased half-lives and long-lasting dose-response. Thus these conjugates may be useful for enhancing the therapeutic potential of drugs and should be explored further. PMID- 7863516 TI - Oxidative stress aspects of the cytotoxicity of carbamide peroxide: in vitro studies. AB - Carbamide peroxide is the active ingredient in many at-home patient-applied tooth whiteners. The cytotoxicity of carbamide peroxide, as related to oxidative stress, was evaluated in vitro with several human cell lines, including Smulow Glickman (S-G) gingival epithelial cells. The potency of carbamide peroxide was related to its hydrogen peroxide component rather than to carbamide, was eliminated in the presence of exogenous catalase, and was enhanced in the presence of aminotriazole, an inhibitor of cellular catalase. The intracellular level of glutathione, a scavanger of toxic oxygen metabolites, was decreased in cells exposed to carbamide peroxide; at higher concentrations of carbamide peroxide, leakage of lactic acid dehydrogenase was also evident. Cells pretreated with the glutathione-depleting agents, buthionine sulfoximine, chlorodinitrobenzene, and bis(chloroethyl) nitrosourea, were hypersensitive to subsequent challenge with carbamide peroxide. Conversely, pretreatment with the iron chelator, deferoxamine, protected the cells against subsequent exposure to carbamide peroxide. PMID- 7863517 TI - Possible involvement of a neurotrophic factor during the early stages of organophosphate-induced delayed neurotoxicity. AB - Little is known regarding early biochemical events in organophosphate-induced delayed neurotoxicity (OPIDN) except for the essential inhibition of neurotoxic esterase (NTE). We hypothesized that a trophic factor may be produced in situ shortly after exposure to the OP which participates in the progression of OPIDN. To bioassay for such a growth-modulating factor(s), we treated chickens with the neuropathic agents diisopropylfluorophosphate (DFP) or cyclic phenyl saligenin phosphate (PSP), with or without phenylmethylsulfonyl fluoride (PMSF, a chemical which markedly modifies OPIDN). Soluble extracts of cervical spinal cord (a region of the nervous system which degenerates with OPIDN) were collected 24 h later and these were incubated with human neuroblastoma SY5Y cells in culture. The cells were allowed to grow for another 6 days and observed for changes in morphology and growth. After 3 days in culture, tissue extracts from OP-treated chickens caused SY5Y cells to begin to elongate and extend processes (neurites), similar to cells treated with nerve growth factor (1 microgram/ml). Extracts from chickens not receiving OP had no or minimal effects on cell morphology. In addition, extracts from chickens in which OPIDN was prevented by pretreatment with PMSF did not cause the marked extension of cell processes exhibited after exposure of SY5Y cells to extracts from chickens given regimens known to cause OPIDN. In parallel-treated animals. DFP and PSP caused clinical dysfunction characteristic of OPIDN, PMSF posttreatment markedly amplified the clinical deficits and PMSF pretreatment prevented OPIDN. In vivo DFP treatment also caused a marked reduction in the activity of the growth-related enzyme ornithine decarboxylase (ODC) in spinal cord but DFP was without effect on ODC activity in vitro (up to 1 mM final concentration). Characterization of this growth modulating factor(s) may aid in the elucidation of pathological mechanisms of OPIDN. PMID- 7863518 TI - Comparative activation of aflatoxin B1 by mammalian pulmonary tissues. AB - Occupational exposures to respirable dusts contaminated with the mycotoxin aflatoxin B1 (AFB1) have been associated with an increased incidence of upper airway tumors. To investigate this possible etiology we compared the abilities of tracheal and lung S9 from rabbit, hamster and rat to activate AFB1 to mutagens in Salmonella typhimurium TA 98. The activation of AFB1 was compared to that of benzo[a]pyrene (B[a]P), a known respiratory carcinogen. These species differ in airway morphology with respect to numbers of metabolically-active non-ciliated tracheal epithelial cells. Tracheas from hamster and rabbit and lung from rabbit were active in converting AFB1 to bacterial mutagens. Trachea from hamster was more efficient in activating AFB1 to mutagens than lung, while rabbit lung was over 4 times more active in converting AFB1 to mutagens than that from trachea. In all cases, AFB1 was more mutagenic than B[a]P. The relative capabilities of trachea to activate AFB1 were in agreement with the ability of cultured tracheas from these species to form to AFB1-DNA adducts. These results demonstrate that AFB1 is activated more efficiently than B[a]P in the lung, and that the metabolic capabilities of airway epithelium to activate AFB1 are not predictable by airway morphology. PMID- 7863519 TI - Tobramycin gender-related nephrotoxicity in Fischer but not Sprague-Dawley rats. AB - Published reports suggest a gender-related difference in susceptibility to the nephrotoxicity of gentamicin which may also be strain-related in rats. However, certain ambiguities exist in the results obtained with the functional and morphologic determinants of nephrotoxicity used in these studies. Within the same experimental protocol we examined the potential gender-related differences in tobramycin nephrotoxicity in age-matched male and female rats of both the Sprague Dawley (SD) and Fischer (F344) strains. Equal numbers of both genders were dosed at 30 mg/kg (F344) and 90 mg/kg (SD) twice daily for 9 days. Results of BUN, serum creatinine, whole body weight change and histologic score comparisons (P < 0.05) indicate that male F344 rats are more sensitive to tobramycin nephrotoxicity than F344 females but this gender-related susceptibility was not observed in SD rats. PMID- 7863520 TI - In vitro toxicity of methyl mercury: effects on nerve growth factor (NGF) responsive neurons and on NGF synthesis in fibroblasts. AB - The effect of methyl mercury chloride (MeHgCl) on the chick sympathetic and sensory dorsal root ganglia was studied in a biological in vitro assay. These cultures were not affected by the addition of MeHg up to a concentration of 2 microM. However, after an addition of 4-5 microM MeHg the capability of the neurons to respond to added nerve growth factor (NGF) was completely inhibited. The effect of MeHg was also examined in a fibroblast cell line, mouse 3T3 cells. After the addition of mercury to the culture medium at concentrations as low as 0.1 microM, an elevated production of the NGF protein was observed. However, NGF mRNA measured in the individual fibroblast cells by in situ hybridization was found to be reduced to about 80% of the control in the low level at day 2 of exposure. These results suggest that the release of NGF is actively enhanced from the 3T3 cells by addition of low levels of mercury. The results thus show that MeHg at low to moderate concentrations has adverse effects on NGF responses in cultured neurons and moreover alter levels of NGF production in cells, suggestive of mechanisms for mercury toxicity in the developing nervous system. PMID- 7863521 TI - Effects of phyllosilicate clay on the metabolic profile of aflatoxin B1 in Fischer-344 rats. AB - The phyllosilicate clay, hydrated sodium calcium aluminosilicate (HSCAS), has been shown to prevent aflatoxicosis in farm animals by reducing the bioavailability of aflatoxin. The present study was designed to determine the effects of HSCAS on the metabolism of aflatoxin B1 (AFB1) in an aflatoxin sensitive species. Male Fischer-344 rats were orally dosed with 1.0, 0.5, 0.25 and 0.125 mg AFB1/kg body weight alone and in combination with 0.5% HSCAS. Urine samples were collected after 6, 24, 36, and 48 h. Aflatoxin M1 (AFM1) and aflatoxin P1 (AFP1) were detected in most urine samples, with or without HSCAS. AFM1 was found to be the major metabolite. Metabolite concentrations were significantly decreased in the presence of HSCAS, and more importantly, no additional metabolites were detected. Our results suggest that the AFB1-HSCAS complex was not significantly dissociated in vivo, and support earlier findings that HSCAS tightly binds aflatoxin. PMID- 7863522 TI - Transplacental pharmacokinetics of a synthetic retinoid which is not bound by mouse embryonic cellular retinoic acid-binding protein. AB - Teratogenicity is a major side effect of retinoids, a class of compounds used in dermatology and oncology. The binding of retinoids to cellular retinoic acid binding protein (CRABP) has been suggested to be important for the mechanism of retinoid embryopathy. Here data are presented on the transplacental pharmacokinetics of CD394 (4-[3-(1-adamantyl)-4-methoxybenzamido] benzoic acid) which does not bind to murine embryonic CRABP, although it is active in rat whole embryo culture and teratogenic in the rabbit in vivo. A single intragastric dose of CD394 (10 mg/kg) was administered to mice on day 11 of gestation. The extent of placental transfer of CD394, determined by HPLC, resembled more that of 13-cis retinoic acid which also does not bind to CRABP, than that of the CRABP-binding all-trans-retinoic acid. CMax values of CD394 obtained after 1-2 h were: 1368 +/- 652 ng/ml for plasma, 203 +/- 132 ng/g for embryo and 856 +/- 563 ng/g for placenta. AUC (area-under-the-concentration-time-curve) values (0-12 h) were: 4319 ng x h/ml for plasma, 751 ng x h/g for embryo and 3163 ng x h/g for placenta. Thus, CD394 reached the embryo, although embryonic AUC values were less than one fifth of the maternal plasma AUC values. CD394 did not alter endogenous retinol concentrations in plasma, embryo, yolk sac or placenta. Our results indicate that CD394 reaches the embryo in vivo without binding to CRABP, although embryonic concentrations stayed well below plasma levels. This supports the opinion that binding to embryonic CRABP is not a prerequisite for reaching effective embryo concentrations and for the teratogenicity of retinoids. PMID- 7863523 TI - Quantitative structure activity relationships for skin corrosivity of organic acids, bases and phenols. AB - Quantitative structure activity relationships (QSARs) have been derived relating skin corrosivity data of organic acids, bases and phenols to their log(octanol/water partition coefficient), molecular volume, melting point and pKa. Datasets were analysed using principal components analysis; plots of the first 2 principal components of the above parameters, which broadly model skin permeability and cytotoxicity, for each group of chemicals showed that the analysis was able to discriminate well between corrosive and non-corrosive chemicals. The derived QSARs should be useful for the prediction of the skin corrosivity potential of new or untested chemicals. PMID- 7863524 TI - Effect of dietary antioxidants on dieldrin-induced hepatotoxicity in mice. AB - An increasing number of reports suggest that oxidative stress plays a role in the toxicity of various xenobiotics, including organochlorine pesticides and drugs such as phenobarbital. Antioxidants appear to be protective against the damage induced by an acute dose of endrin, supporting the theory of a role for reactive oxygen in the toxicity of this class of compounds. The current study examined the effects of the dietary administration of vitamin C (400 mg/kg diet) or vitamin E (200 mg DL-alpha-tocopherol acetate/kg diet) on hepatotoxicity induced by subchronic (7 or 28 days) feeding of dieldrin (1, 3 and 10 mg/kg diet) to male B6C3F1 mice. Hepatoxicity induced by feeding of dieldrin for 28 days was evidenced by liver enlargement, hypertrophy of centrolobular hepatocytes, induction of hepatic ethoxyresorufin O-deethylase activity, and increased DNA synthesis in hepatocytes, particularly in centrolobular hepatocytes. Neither vitamin inhibited the dose-dependent increase in liver/body weight ratios, hypertrophy of centrolobular hepatocytes, or induction of hepatic ethoxyresorufin O-deethylase. Vitamin E, however, inhibited hepatic DNA synthesis at all dietary intakes of dieldrin, while vitamin C was inhibitory at 1 and 3, but stimulatory at 10 mg dieldrin per kg diet. The major changes in DNA labeling occurred in the centrolobular zones, but were not consistently inhibited by vitamins C or E. The ability of antioxidant vitamins to inhibit dieldrin-induced hepatic DNA synthesis suggests oxidative stress is involved in the toxicity of this compound; however, the inability of these vitamins to prevent all hepatotoxic changes indicates other factors are also involved. PMID- 7863525 TI - Chronic inhalation exposure and phospholipids in lung surfactant and tissue. AB - Golden hamsters were exposed to 2 mg/m3 coal fly ash for 180 days. The exposure raised the phospholipid level in the tissue, whereas no such elevation was observed in the surfactant. Increased phospholipid in the tissue is thought to reflect the accumulated surfactant in type II cells. Fatty acid composition analysis indicated an increase of arachidonic acid in the surfactant and increases of palmitic acid and arachidonic acid in the tissue. In conclusion, the pulmonary surfactant high in fluidity was stored in the lung tissue more than control, and the surfactant was secreted into the alveoli normally. PMID- 7863526 TI - Metabolic, cardiovascular, and neurologic aspects of acute cyanide poisoning in the rat. AB - Acute cyanide (CN) toxicity was investigated in the Sprague-Dawley rat. Conscious, loosely restrained rats received sodium CN solution at varying dose rates through a jugular cannula (low CN, 0.077-0.155 mg/kg/min; high CN, 0.157 0.204 mg/kg/min). Blood glucose concentration was significantly increased 45 min after initial CN treatment in both the low and the high CN groups compared to the saline controls. Blood lactate concentration was significantly increased only in the high CN group after 45 min. Lactate increased directly with CN dose rate in surviving high CN rats. In rats that succumbed during CN infusion, lactate concentration reached nearly 150 mg/dl. Body temperature decreased modestly at low CN dose rates, but increased markedly at high CN dose rates. Heart rate was relatively constant in the low CN group, but decreased rapidly in the high CN group with increasing CN dose rate. In rats surviving CN treatment, no significant alterations in either cerebral cortical water content or neurologic status were detected. This contrasts with another potent poison, carbon monoxide, which produces marked neurologic deficit and cerebral edema in this animal model. The mean lethal CN dose was 4.6 mg/kg (range 4.25-4.90 mg/kg). Expressed on the basis of CN infusion rate, the lethal zone was from 0.16 to 0.21 mg/kg/min, a surprisingly narrow range. Assuming that extrapolations are possible to other species, the data provide strong evidence that greatly elevated blood lactate may be a useful marker for CN poisoning very near or within the lethal zone. PMID- 7863527 TI - Anchorage independent colony growth of fetal hamster lung epithelial cells after treatment with diepoxybutane. AB - To test the reliability of a new cell transformation assay, a cloned fetal Syrian hamster lung epithelial cell line (M3E3/C3) was used. The target cells originating from the respiratory tract were treated in vitro over a concentration range of 0-10(-5) M/l with diepoxybutane, cultured during the expression period of 28 or 35 days and then transferred into soft agar. Anchorage independent colony growth in soft agar occurs only if cells are transformed. Growth and number of colonies were taken as a score of the carcinogenic potential of the test substance. Under the conditions of this cell transformation assay it was possible to detect the carcinogenic potential of diepoxybutane unequivocally. PMID- 7863528 TI - 32P-postlabeling analysis of adducts formed between DNA and safrole 2',3' epoxide: absence of adduct formation in vivo. AB - We have used the 32P-postlabeling technique to examine the binding of safrole 2',3'-oxide to DNA. At least 8 covalent adducts are formed when calf thymus DNA is incubated with this oxygenated metabolite of safrole in vitro. However, no corresponding adducts are formed with liver DNA when whole animals are exposed to safrole 2',3'-oxide, or safrole itself. Although safrole 2',3'-oxide is readily formed in vivo, and is sufficiently reactive to covalently bind to DNA, it is probably not a factor in the in vivo genotoxicity of safrole. We also demonstrate that adducts with similar mobility to the major safrole 2',3'-oxide-DNA adduct are formed in vitro between safrole 2',3'-oxide and deoxyguanosine, and also between its chemical analogs allylbenzene 2',3'-oxide or estragole 2',3'-oxide and DNA. PMID- 7863529 TI - Short- and long-term biochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Long-Evans rats. AB - The aim of this study was to examine short- and long-term biochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in female Long-Evans (L-E) rats. In the short-term study, female rats were dosed orally with 5.3, 12, 18 and 60 micrograms TCDD/kg and sacrificed 4 days after dosing. In the long-term study, rats were dosed with 27, 40 and 60 micrograms TCDD/kg and sacrificed 90 days after dosing. Four days after dosing, ethoxyresorufin O-deethylase (EROD) activity was fully induced at all doses studied, hepatic phosphoenolpyruvate carboxykinase (PEPCK) and gamma-glutamyl transpeptidase (gamma-GT) activities were dose-dependently reduced, whereas hepatic tryptophan 2,3-dioxygenase (TdO) activity was stimulated at low doses but decreased at high doses. Serum total T4 (TT4) levels were dose-dependently decreased, whereas serum total T3 (TT3) and tryptophan levels were unaffected. The short-term effects of TCDD examined in this study indicate only small differences in the response of female L-E rats to TCDD as compared to males. Ninety days after dosing, liver EROD activity revealed considerable reversibility although it was still elevated compared to controls. Hepatic PEPCK activity at this time point was no more different from controls. In contrast to 4 days after dosing, serum TT3, TT4 and hepatic gamma-GT activity were dose-dependently elevated at the 90-day time point. These findings have significant implications for the interpretations of subchronic and chronic effects of TCDD on thyroid homeostasis and on the formation of preneoplastic liver foci. PMID- 7863530 TI - Metabolic transformation of halogenated and other alkenes--a theoretical approach. Estimation of metabolic reactivities for in vivo conditions. AB - Olefinic hydrocarbons are metabolized in vivo by cytochrome P450-dependent monooxygenases to the corresponding epoxides. The maximum in vivo metabolic rate, which is an important toxicokinetic parameter, has been used to define the apparent rate constant (kapp) describing in vivo metabolic reactivity of alkenes. To derive kapp, the metabolic rate normalized per body weight was divided by the corresponding average alkene concentration in the body at saturation conditions of 90%. Toxicokinetic data obtained in rats for 13 compounds (ethene, 1 fluoroethene, 1,1-difluoroethene, 1-chloroethene, 1,1-dichloroethene, cis-1,2 dichloroethene, trans-1,2-dichloroethene, 1,1,2-trichloroethene, perchloroethene, propene, isoprene, 1,3-butadiene and styrene) have been used to calculate kapp values. A theoretical model, based on the assumption that in vivo epoxidation can be described as a cytochrome P450-mediated electrophilic reaction, has been developed. Using the olefinic hydrocarbons as an example it has been shown that kapp can be explained solely by the following molecular parameters: ionization potential, dipole moment and pi-electron density. These molecular parameters were calculated by a quantum chemical method or were taken from the literature. Furthermore, the model was tested also by predicting kapp for isobutene, an alkene which was not used for the model development. The predicted value of kapp agrees with the one derived experimentally, demonstrating that molecular parameters of halogenated and other alkenes can be used to predict in vivo metabolic reactivity. The model presented here is a first contribution to the ultimate goal to predict toxicokinetic parameters for in vivo conditions based on physicochemical parameters of enzymes and compounds exclusively. PMID- 7863531 TI - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on interleukin-4-mediated mechanisms of immunity. AB - Because of similarities in the independent actions of the pleiotropic cytokine, interleukin-4 (IL-4), and the environmental contaminant, 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), on murine B-lymphocytes suggested in earlier studies, we have investigated whether the immunosuppression mediated by direct exposure to TCDD in vitro is due to an IL-4-like biological activity. In particular, the ability of TCDD to mimic hallmark responses of B-cells to IL-4, such as upregulation of major histocompatibility complex (MHC) antigens of the class II type, increases in cell surface expression of the low affinity form of the Fc receptor for IgE (CD23) and induction of immunoglobulin class switching, was tested. At concentrations that readily suppress B-cell proliferative and antibody-forming cell responses, TCDD failed to demonstrate any of the activities of IL-4 observed in parallel cultures. Further, in experiments in which TCDD was preincubated with B-cells before addition of IL-4, no evidence of increased IL-4 activity was observed. Rather, TCDD preincubation resulted in decreased secretion of IgG1 and IgE in B-cell cultures stimulated to undergo immunoglobulin class switching by incubation with bacterial lipopolysaccharide (LPS) and IL-4. Because TCDD produced comparable suppression of IgM secretion induced by LPS alone (i.e., no IL-4), it appears that TCDD inhibits the formation of fully differentiated B cells capable of secreting antibody and has no effects on class switching events per se. Coupled with previous reports from this and other laboratories, these observations indicate that TCDD is able to suppress secretion of several classes of immunoglobulin. PMID- 7863532 TI - The effects of disulfiram on the hippocampus and cerebellum of the rat brain: a study on oxidative stress. AB - The purpose of this investigation was to study the relationship between disulfiram (DS) toxicity, lipid peroxidation, and copper in order to further elucidate the mechanisms of DS toxicity. Male Sprague-Dawley rats were dosed with either 375, 750 or 1500 mg/kg disulfiram via oral intubation for 1, 3 and 6 weeks. In the hippocampus and cerebellum, the increased accumulation of copper, increased production of malondialdehyde (MDA), increased activity of glutathione peroxidase along with alterations in glutathione and glutathione disulfide concentrations was indicative of oxidative stress. The production of MDA was directly related to the level of copper in both areas of the brain indicating that excess copper may be the primary cause of DS neurotoxicity. PMID- 7863533 TI - Commentary on the minireview by A.B. Okey, D.S. Riddick and P.A. Harper. PMID- 7863534 TI - Ah receptor role in TCDD toxicity: still some mysteries but no myth--a reply to the commentary by Dr. L.W.D. Weber and Dr. B.U. Stahl. PMID- 7863535 TI - Assessment of the neurotoxicity of styrene, styrene oxide, and styrene glycol in primary cultures of motor and sensory neurons. AB - The neurotoxicity of styrene and its major metabolites, styrene oxide and styrene glycol, was investigated in dissociated primary cultures of murine spinal cord dorsal root ganglia (DRG)-skeletal muscle using morphological and electrophysiological endpoints. Styrene and styrene oxide (but not styrene glycol) were acutely cytotoxic to both neuronal and non-neuronal cells in the cultures; concentrations in excess of 2 and 0.2 mM, respectively, induced blebbing, vacuolation, detachment from the substratum and cell death in neuronal and non-neuronal cells within 4 days. No effects on neuronal morphology were observed in cultures treated with sublethal concentrations of styrene or styrene oxide for up to 3 weeks. The results suggest that oxidation of multiple cellular macromolecules that underlies the toxicity of styrene in other organ systems may also be responsible for damage to cells in the nervous system. No changes in action potential production indicative of a 'solvent effect' on membrane electrical properties was apparent in cultures treated with up to 8 mM styrene or 10 mM styrene glycol. PMID- 7863537 TI - Tissue concentrations of methyl isobutyl ketone, methyl n-butyl ketone and their metabolites after oral or inhalation exposure. AB - Quantitative relationships between plasma, liver and lung methyl isobutyl ketone (MiBK) and methyl n-butyl ketone (MnBK) concentrations after oral or inhalation exposure were established. Their respective metabolites (4-methyl-2-pentanol, 4 hydroxy-methyl isobutyl ketone, 2-hexanol, and 2,5-hexanedione) were also quantified. Male Sprague-Dawley rats were exposed for 3 days to MiBK or MnBK vapors (4 h/day) or treated orally for 3 days with a MiBK- or MnBK-corn oil solution. Both ketones and their respective metabolites in plasma or tissue concentrations were determined by gas chromatography. MiBK and MnBK plasma and tissue concentrations increased in a dose-related manner with the administered dose irrespective of the route of administration. Metabolite concentrations, however, were influenced by the route of administration. PMID- 7863536 TI - Mechanism of caffeine modulation of the antitumor activity of adriamycin. AB - We examined the effects of a combination of adriamycin (ADR) and caffeine on DNA and protein biosynthesis and on the activities of DNA polymerase alpha and beta in normal and tumor tissue. The decrease in DNA and protein biosynthesis in tumor produced by caffeine combined with ADR were 2.5 and 2.4 times greater, respectively, compared with ADR alone. The combination of caffeine and ADR enhanced the decrease in DNA polymerases activities in the tumor which was induced by ADR, the decreases being 1.8 and 1.6 times greater, respectively, than that of ADR alone. In contrast, these ADR-induced changes in normal tissues were not enhanced by the combination with caffeine. The combination with caffeine had no effect on ADR concentration in normal tissues, but in the tumor, it increased the ADR concentration to 2.1 times that of ADR alone. In vitro, ADR efflux from Ehrlich ascites carcinoma cells was significantly inhibited by exposure to caffeine. These findings indicate that the effect of caffeine on ADR concentration in the cell plays an important role in the mechanism by which caffeine enhances ADR antitumor activity. PMID- 7863538 TI - Effect of propylene glycol 1,2-dinitrate on cerebral blood flow in rats: a potential biomarker for vascular headache? AB - Two measurable indices of toxicity that can be correlated with exposure to propylene glycol dinitrate (PGDN) were evaluated along with its metabolism. Propylene glycol dinitrate was administered by rapid i.v. injection to male Fischer-344 rats. These rats demonstrated a dose-response of blood pressure (BP) to doses of PGDN ranging from 0.1 to 30 mg/kg; the maximum fall in systolic BP occurred within 1 min of dosing. The i.v. administration of PGDN to separate groups of animals resulted in an increase in cerebral blood flow that was correlated with the dose, but a clear dose-response was not obtained. PMID- 7863539 TI - Effects of vindesine on hypothalamic-pituitary-adrenal axis. AB - Vindesine, a cell-cycle-specific agent currently employed in the treatment of some neoplasias, was able to produce a remarkable dose-dependent adrenocortical activation, but it was unable to increase plasma corticosterone in hypophysectomized rats in vivo. In addition, vindesine was able to increase ACTH release in vitro when tested on isolated pituitary cells in culture suggesting a direct involvement of the pituitary gland in the increase of adrenal secretion in vivo. PMID- 7863540 TI - Renal damage caused by gentamicin: a study of the effect in vitro using isolated rat proximal tubular fragments. AB - The clinical use of gentamicin (G) is limited because of its nephrotoxic potential. The administration of G (50 mg/kg) to rats in a 10-day daily treatment gave a biphasic pattern of lactate dehydrogenase (LDH) and N-acetyl-beta-D glucosaminidase (NAG) excretion. Alkaline phosphatase (ALP) was highly elevated during the corresponding second phase while a slight and statistically insignificant increase in glutamate dehydrogenase (GDH) was obtained. The kidneys of such rats were isolated and tubules prepared and incubated for a specific period of time at 37 degrees C in Kreb's Henseleit bicarbonate buffer, pH 7.4. Results indicate a considerable loss of protein (P < 0.01) after the 3rd and 10th days of treatment with G, elevated and significant increase of ALP after the 1st (P < 0.05) and 3rd (P < 0.01) days and significant increase (P < 0.05) of GDH after the 10th day of treatment. The release of GDH, LDH and NAG from tubules of rats after a single dose of G was lower than the control rats while other treatments produced a significant increase in ALP, LDH and NAG over the period of incubation. In vitro incubation of tubules in the presence of several concentrations (5, 50, 500, 5000 micrograms/g of wet cortex) of G indicated a time-dependent leakage of enzyme only at the highest concentration of G. Our results clearly indicate that cellular damage caused by G as evidenced by urinary enzyme excretion and marker enzyme release from isolated tubules occurs at very high concentration in vivo or in vitro and is time-dependent. PMID- 7863541 TI - Zinc-induced tolerance to cadmium cytotoxicity without metallothionein induction in cultured bovine aortic endothelial cells. AB - We investigated the cytotoxicity of cadmium in cultured vascular endothelial cells from bovine aorta pretreated with zinc. The cytotoxicity was evaluated by the [3H]adenine release assay. It was shown that the increase in the [3H]adenine release after challenge with cadmium was significantly prevented by pretreatment with zinc. It was histologically observed that cadmium-induced occurrence of the de-endothelialized areas was reduced in zinc-pretreated cell layer. Intracellular accumulation of cadmium was significantly less but that of zinc was more in zinc pretreated cells. The content of cadmium in both the particulate and the cytosol fraction was decreased by zinc pretreatment; however, metallothionein content after challenge with cadmium was not changed. It was therefore concluded that zinc is capable of inducing a tolerance to cadmium cytotoxicity in cultured vascular endothelial cells; this tolerance is postulated to be due to a decrease in the intracellular cadmium accumulation rather than a metallothionein induction. PMID- 7863542 TI - The influence of dihydrodiol conformation on the metabolic activation of cyclopenta[a]phenanthrenes. AB - The present study was undertaken in order to rationalise the apparent biological inactivity of 15,16-dihydro-6-methylcyclopenta[a]phenanthren-17- one (4) when other methyl isomers of 15,16-dihydrocyclopenta[a]phenanthren- -17-one, e.g. the 11-methyl derivative (2), display appreciable tumorigenicity. In vitro metabolism of the 6-methyl-ketone-17-one (4) demonstrated that its principal metabolite was the 3,4-dihydro-3,4-diol (3,4-dihydroxy-6-methyl-3,4,15,16- tetrahydrocyclopenta[a]phenanthren-17-one) (5) which, in the case of the active 11-methyl derivative, is the proximate genotoxin. Thus the inactivity of this 6 methyl-17-ketone cannot be ascribed to lack of formation of the 3,4-dihydro-3,4 diol, the precursor of the 3,4-diol-1,2-epoxides (the ultimate mutagens in this series). However, the 6-methyl-3,4-dihydro-3,4-diol exists in a pseudo-diaxial rather than a pseudo-diequatorial conformation characteristic of the 3,4-dihydro 3,4-diols of the other members of the series. It is therefore suggested that a diequatorial conformation in the dihydrodiol is essential to the metabolic activation of the cyclopenta[a]phenanthren-17-ones. PMID- 7863543 TI - Thymic repertoire selection by superantigens: presentation by human and mouse MHC molecules. AB - The initial report of T cell receptor (TCR) V beta-specific thymic selection in mice showed association with expression of H-2E molecules and affected V beta 17a T cells which were present in CD4+8+ double positive thymocytes but deleted from the CD4+ and CD8+ single positive populations. Similar deletions were subsequently reported for V beta 8.1+ and V beta 6+ T cells in Mls-1a mouse strains and for V beta 3+ T cells in Mls-2a/3a strains. The 'Mls antigens' are most effectively presented by H-2E molecules but certain alleles of H-2A molecules can also present these endogenous superantigens. Expression of Mls antigens can cause both V beta-specific thymic deletion and stimulation of peripheral T cells from Mls-negative strains. Another category of 'Mls-like' antigens cause only V beta-specific thymic deletion in H-2E+ strains, affecting V beta 5+ and V beta 11+ T cells. The non-MHC ligands responsible for each of these effects are superantigens analogous to the exogenous bacterial superantigens, which also show TCR V beta-specific stimulatory effects when presented by MHC class II positive antigen-presenting cells. The genes encoding endogenous superantigens in mice were shown to co-segregate with mouse mammary tumour virus integrations (Mtv) and to be the Mtv-LTR orf genes. In vitro translation of Mtv LTR orf genes identified their products as type II integral membrane glycoproteins with the polymorphic C terminus outside the cell. These polymorphisms correlate with specificity for the different TCR V beta chains. Virtually all TCR V beta-specific negative selection in the mouse thymus can be accounted for by the expression of Mtv or MMTV (the infectious counterparts of Mtv proviral integrants) LTR-orf proteins, presented with H-2E or certain H-2A alleles. It is unlikely that TCR V beta-specific positive selection is due to endogenous superantigens since it does not segregate with Mtv genomes. In humans, HLA-DR molecules appear to be homologous with H-2E in mice whereas HLA-DQ are the homologues of H-2A. H-2E negative mice transgenic for HLA-DR alpha chain express a mouse/human heterodimeric molecule which presents Mtv superantigens causing TCR V beta-specific deletion. Such trans-species class II molecules are also effective in TCR V beta-specific positive selection of V beta 2+, V beta 6+ and V beta 10+ T cells. Taken together, these results show that human MHC class II molecules can interact with the murine T cell repertoire.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7863544 TI - Developmental control of T-cell receptor internalization. AB - Since TCR/CD3 modulation may be involved in induction of T cell tolerance to self antigens, we compared ligand-induced TCR/CD3 internalization by a CTL clone and by immature thymocytes and mature T cells from mice bearing the same TCR alpha beta as transgene. The ligand used is a monoclonal antibody (mAb) specific for the receptor expressed by the clone and transgenic mice (anti-Ti mAb). CD8+ splenocytes triggered by anti-Ti mAb internalize the ligand-TCR/CD3 complex at a low rate, through a mechanism inhibited by the protein tyrosine kinase (PTK) inhibitor genistein and by staurosporine, a potent but non selective protein kinase C (PKC) inhibitor. This pattern of inhibition was similar to that observed in the CTL clone. Anti-Ti mAb induced TCR/CD3 internalization in CD4+CD8+ thymocytes at a high rate, through a mechanism which was insensitive to either genistein or staurosporine. In the CTL clone, genistein was shown to inhibit TCR/CD3 surface redistribution preceeding internalization. To characterize the PTK possibly involved in this step, we analyzed TCR/CD3 associated kinases in mature T splenocytes and thymocytes. Kinase activities present in anti-Ti mAb immunoprecipitates phosphorylated the CD3 components gamma, delta, epsilon, and zeta in both cell types although the intensity was stronger in splenic than in thymocyte extracts, whereas the phosphorylation of 70, 14 and 12kD substrates was more pronounced in thymocytes than in splenocytes. Comparable amounts of CD3 components were coprecipitated with and phosphorylated by p56lck and p59fyn respectively, in both cell types. PMID- 7863545 TI - Effects of a multidrug chemotherapy regimen on the thymus. AB - Multidrug chemotherapy regimens are commonly used in the treatment of cancer. The dose limiting tissue for chemotherapeutic treatment is often the bone marrow, as many chemotherapeutic agents selectively target rapidly proliferating cells. Bone marrow transplantation (BMT) has allowed an increase in chemotherapeutic dose; however, this type of therapy is associated with a prolonged suppression of immune function following the BMT. Although it may be possible to augment this immune function, animal models which can be used to test various cytokines have not been well described. We have developed a mouse model of multi-drug chemotherapy which, like the human, demonstrates long term immune suppression following BMT. In this report, we describe the specific effects of this chemotherapy regimen on T cell differentiation in the thymus of treated mice using three color FACS analysis. Results demonstrated that specific populations of thymocytes are extremely susceptible to chemotherapeutic insult. Both thymus cellularity and the immature CD3-CD4+CD8+ double positive population dropped to approximately 3% of their original values by 7 days after chemotherapy initiation. During the same time period, cells expressing both alpha beta and gamma delta T cell receptors demonstrated a 2-6 fold increase in frequency. Similar results were observed for the alpha beta+ CD4-CD8- population of natural suppressor cells. Long-term changes in the proportion of cells expressing the V beta 5 TCR were also observed following chemotherapy. These results demonstrate that chemotherapy regimens may directly influence T cell differentiation within the thymus, and also suggest that long term changes in the T cell V beta repertoire may occur following chemotherapy. PMID- 7863546 TI - Management of hepatic metastases: hope for the hopeless. PMID- 7863547 TI - Hepatic metastases from colorectal cancer: an overview of surgical management. PMID- 7863548 TI - Pancreatic pseudocyst: the changing concepts. PMID- 7863549 TI - Assessment of nutritional status of hospitalized patients. PMID- 7863550 TI - The epidemiologic significance and clinical pattern of HCV induced chronic hepatitis in India. AB - Hepatitis C virus (HCV) ribonucleic acid (RNA) was tested for in a group of 16 defined non-B chronic hepatitis patients using specific reverse transcription polymerase chain reaction (RT-PCR). These were chosen from amongst 56 biopsy proven cases of chronic hepatitis of which majority (40) were positive for hepatitis B virus infection. Hepatitis C virus RNA could be demonstrated in 12 (75%) of remaining 16 cases. These include all seven patients positive for antibody to HCV. Two of these patients had past history of blood transfusion and in another two the clinical course started with severe acute liver disease. This study establishes the association of HCV with severe liver disease. The clinical and biochemical profiles are also discussed. In view of limited sensitivity of the antibody assays it is justified to develop diagnostic testes based on local strains. PMID- 7863551 TI - An audit of pneumatic dilatation and oesophagomyotomy in patients with achalasia cardia. AB - The role of pneumatic dilatation and oesophagomyotomy in the management of achalasia cardia was evaluated. Twenty patients with achalasia cardia managed either by pneumatic dilatation (n = 10) and oesophagomyotomy (n = 10) were studied. Patients undergoing dilatation were followed up for a mean of 20 months (12-30 months) and those undergoing myotomy for 17 months (6-48 months). The patients were evaluated clinically, radiologically and endoscopically. Relief of dysphagia was excellent in 20%, good in 50% and fair in 30% of those who underwent dilatation. In the myotomy group, 60% had an excellent result, 30% had a good result and fair results was observed in 10%. Oesophagitis on endoscopic evaluation, was found in two patients in myotomy group. The diameter of the gastro-oesophageal junction increased from a mean of 2 mm (range 1 to 4 mm) to a mean of 11 mm (range 4 to 15 mm) in dilatation group while in myotomy group it changed from a mean of 2 mm (range 0.5 to 8 mm) to a mean of 9 mm (range 5 to 15 mm). Symptomatic improvement was better after myotomy than after pneumatic dilatation and correlated poorly with radiological features. PMID- 7863552 TI - Effect of histamine and glucose on encystation of Entamoeba histolytica in vitro. AB - Isolates of Entamoeba histolytica grown and maintained in modified Boeck and Drbohlav's medium were used to examine the effect of histamine and glucose on encystation process in vitro. This revealed that 60-74% of the active and motile trophozoites of E. histolytica encysted within 72 hours in the presence of histamine and glucose, in contrast to 10-20% encystment in controls (with out histamine and glucose); a highly significant difference (P < 0.001). These observations also suggest the possibility of active role of histamine and glucose in encystation of E.histolytica in vivo. PMID- 7863553 TI - Budd Chiari syndrome and pericaval filariasis. AB - A young girl presented with Budd-Chiari syndrome (BCS) with narrowing of the retrohepatic segment of inferior vena cava (VC). Dorsal cavoatrial bypass (DCAB) was unsuccessful due to thrombotic occlusion of the graft. A limited autopsy revealed occlusion of the retrohepatic segment of IVC and the terminal parts of the three major hepatic veins. Caval occlusion was just above the level of the superior hepatic veins, and caused by a transverse fibrous shelf. An adult filarial worm was found amidst pericaval fibrosis. Filariasis should be included as a possible aetiological factor in chronic BCS. PMID- 7863554 TI - Traumatic eventration of diaphragm complicated by mesenteroaxial volvulus of the stomach. AB - Diaphragmatic disruption is an uncommon consequence of blunt trauma and is often overlooked unless there is a high index of clinical suspicion. A case of eventration of left dome of diaphragm following trauma with mesenteroaxial volvulus of the stomach is presented. Anatomical considerations on levels of diaphragm on chest x-ray has been elaborated. PMID- 7863555 TI - Radiation induced hemorrhage proctitis: a vexing problem. PMID- 7863556 TI - Three-dimensional and four-dimensional echocardiography. AB - Since its introduction in 1974, 3-D reconstruction of the heart has undergone significant technological refinements in image acquisition, processing and display techniques. Image acquisition for transthoracic 3-D reconstruction utilizes the parasternal or apical windows, or combinations of the two. The parasternal approach allows better endocardial border detection, while the apical approach allows a more complete visualization of the left ventricular apex. Computer algorithms are used to process images with various display techniques incorporated into the algorithm. Transesophageal image acquisition overcomes a significant limitation of the transthoracic approach, which is variable and sometimes poor image quality. Both a multiplane approach and a computerized tomographic approach have been successfully used by several investigators. Potential applications of 3-D echocardiography include reconstruction of the mitral annulus, dynamic cardiac anatomy and function and volume calculations. A major limitation is the need for considerable computer time for image processing and display; furthermore, errors may be introduced by the various smoothing and contouring algorithms. Despite these limitations, 3-D echocardiography has considerable potential for clinical utility, particularly in the areas of reconstructive cardiac surgery and congenital heart disease. PMID- 7863557 TI - A comparative assessment of cerebral haemodynamics in the basilar artery and carotid territory by transcranial Doppler sonography in normal subjects. AB - In 69 healthy volunteers (34 males, 35 females, age range 17-80 years) we compared the following haemodynamic parameters between the basilar artery and carotid artery system, assessed by transcranial Doppler sonography: mean blood velocity, pulsatility index and the hemispheric indices as ratios of the middle, anterior and posterior cerebral arteries with the internal carotid artery (MCA/ICA, ACA/ICA, PCA/ICA) and of the PCA with the basilar artery (PCA/BA), as well as the ACA/MCA and the MCA/BA ratio. In all arteries (ICA, MCA, ACA, PCA and BA) mean blood velocity decreased significantly with advancing age (p < 0.01) and was significantly higher in females as compared to males (p < 0.05). The pulsatility index increased significantly with age in the ICA, MCA, ACA and BA (p < 0.01) and showed no sex differences in any of the intracranial arteries except for the ACA. The MCA/ICA and ACA/ICA index declined significantly with advancing age (p < 0.005, p < 0.05, respectively) and with increasing heart rate (p < 0.01 for both arteries), while the ACA/MCA, the PCA/BA and the MCA/BA ratio remained unchanged by age and heart rate. We conclude that there is no striking difference in the cerebral haemodynamics of the basilar artery and the carotid artery supplied territories. PMID- 7863558 TI - Intracranial aneurysms and arteriovenous malformations: transcranial colour-coded sonography as a diagnostic aid. AB - Transcranial colour-coded sonography (TCCS) is a new development in noninvasive cerebral vascular imaging. We studied 5 patients with known intracranial aneurysms and 12 patients with arteriovenous malformations (AVM). We were unable to image any of the aneurysms (all 5 mm or less in diameter) using colour flow ultrasound. Similarly, pulsed wave Doppler interrogation failed to reveal any flow disturbances. Nine out of 12 AVMs were successfully visualised as serpiginous structures and the principal feeder vessels were identified in 11 cases. Blood flow velocities in the feeder vessels were elevated compared with the same vessel contralaterally (median [cm/s]; peak systolic 227 vs. 89, P = 0.001; mean 178 vs. 57, P = 0.001; end diastolic 138 vs. 37, P < 0.0005). Pulsatility indices (PI) and resistance indices (RI) in the feeder vessels were reduced relative to the same vessel contralaterally (median PI 0.46 vs. 0.94, P < 0.0005; median RI 0.37 vs. 0.59, P < 0.0005). At present, TCCS appears of little value in the diagnosis of intracranial aneurysms, but it shows promise for the imaging of AVMs and their haemodynamic study. PMID- 7863559 TI - The influence of ultrasound scanner beam width on femur length measurements. AB - Systematic differences have been found in measurements of femur lengths made with (1) a Hitachi EUB 25, representative of older machines in use when most of the femur length-gestation curves were produced; and (2) a modern high resolution machine (Acuson 128). It is proposed that these differences may be accounted for by the different beam widths of the two systems. Six operators measured the femur lengths of several normal fetuses using both machines. Analysis of the results revealed a highly significant (p < 0.005) difference between machines, that did not correlate with femur length (r = -0.022). The mean difference was 1.02 +/- 0.33 mm (Hitachi larger). The mean femur length was 46.44 mm (n = 57). Pulse-echo beam plots showed that, for the probes used, the Hitachi 6 dB beam width is greater than the Acuson beam width by typically 2 mm, depending on the range and Acuson focus setting. This beam width difference can account for the difference in femur length measurements, if allowance is made for the variable angle between femurs and ultrasound beams. The results suggest that femur length-gestation curves for use with modern machines should be based on measurements made with modern machines. PMID- 7863560 TI - A practical clinical method for contour determination in ultrasonographic prostate images. AB - This paper describes a practical method for automated determination of the contour of the prostate in ultrasonographic images. In this method, we use specific edge detection techniques, based on nonlinear Laplace filtering. Possible edges are located at zero-crossings of the second derivative of the image. The strength of the edge is reflected by the value of the gradient of the image at that location. Combining the information about location and strength, an edge intensity image is constructed from the initial ultrasonographic image. In our method, edge enhancement techniques are performed on the edge intensity image. Edges that actually represent a boundary are selected and linked: interpolation techniques are used to fill the gaps between detected boundary edges. The method for contour determination in ultrasonographic images is used for accurate volume measurements in an everyday clinical environment. Its computer implementation is fast, accurate (mean difference within 6% of exact volume) and easy to use. PMID- 7863561 TI - Ultrasonic three-dimensional reconstruction: in vitro and in vivo volume and area measurement. AB - This study validates the use of an ultrasound three-dimensional reconstruction system to measure phantom and blood conduit geometry. Independently determined uniform and stenotic phantom dimensions are compared with reconstruction-based measurements. Lower extremity saphenous vein bypass graft reconstructions were performed to demonstrate clinical application. Uniform phantom independent and reconstructed volume correlation was high (r = 0.989), the average volume difference was 4.68 mm3 and the average area difference was 0.4 mm2. An in vitro 28% diameter reduction was detected. Stenotic bypass graft segment volume was 795 mm3; following successful angioplasty the volume increased to 1419 mm3. Advantages of this technique are its accuracy, the luminal information it provides and the absence of mechanical arm or acoustic transmitter limitations. We are exploring the possibility that measurement of luminal change over time may allow stenosis detection prior to hemodynamic disturbance, in an ongoing clinical saphenous vein bypass graft surveillance study. PMID- 7863562 TI - Pseudocolor B-mode arterial images to quantify-echogenicity of atherosclerotic plaque. AB - Based on the differences between tissue impedances in atherosclerotic plaques and on the scattering of ultrasound from blood, colors were assigned to the echo strength scale, replacing the usual gray scale in 2-D B-mode ultrasound images. Using a "green tag" indicating -55 dB to mark blood, other echo strength values from atherosclerotic plaque were assigned specific colors, creating a B-mode color ultrasound display that highlights selected echogenicities. The color scale permits the use of a wider dynamic range in the B-mode image, and allows the instrument gains to be set reproducibly. PMID- 7863563 TI - Echolucent regions in carotid plaque: preliminary analysis comparing three dimensional histologic reconstructions to sonographic findings. AB - This study compares sonographic and histologic findings within defined spatial regions in carotid artery plaque, using computer generated three-dimensional reconstructions. Twenty-four patients (14 asymptomatic, 10 symptomatic) with angiographically documented 70% to 99% carotid artery stenosis were examined with ultrasonic B-mode imaging prior to endarterectomy. Using a standardized protocol for instrument set-up and scanning technique, echolucent regions in the plaque were identified. After endarterectomy, each plaque was sectioned at 0.5 to 1.0 millimeter increments throughout its length. Sites containing intraplaque hemorrhage, cholesterol clefts, foam cells, necrotic cores, dense calcification and speckled calcification were identified. These areas were outlined on a template, digitized and imported into a computer program that created three dimensional reconstructions of the histologic findings. Each carotid plaque was divided into quadrants for analysis: (1) lateral wall proximal to the common carotid bifurcation (flow divider); (2) medial wall proximal to the flow divider; (3) lateral wall distal to the flow divider; and (4) medial wall distal to the flow divider. The odds of finding intraplaque hemorrhage, foam cells, necrotic cores and speckled calcification were significantly higher in quadrants with an echolucent region identified by ultrasonography (odds ratio (95% confidence interval) for intraplaque hemorrhage = 3.5 (1.4-8.6); foam cells = 4.0 (1.6-9.9); necrotic cores = 3.2 (1.2-8.4); speckled calcification = 4.0 (1.6-9.8). This preliminary analysis demonstrates the potential of these newly developed techniques for comparing ultrasonic imaging to histology. PMID- 7863564 TI - Detection of intraocular pressure change in the eye using sonoelastic Doppler ultrasound. AB - We report the first use of sonoelastic Doppler ultrasound for in vivo and in vitro clinical studies of intraocular pressure (IOP). The method involves low amplitude and low-frequency sonic excitation of the eye, and detection of the resulting vibration using Doppler ultrasound. A dependence of the frequency of resonance of the eye on the IOP has been observed in both in vitro and in vivo experiments. Preliminary in vitro experiments have been performed using eviscerated and enucleated human and pig eyes. As little as 4 mm Hg change in IOP has been found detectable in these experiments. Preliminary in vivo experiments also showed promising results in this regard. We present a simple model for the resonances of the eye, a method to detect the amplitude of vibration using Doppler ultrasound and results from the in vitro and in vivo experiments. PMID- 7863565 TI - Spectral tissue strain: a new technique for imaging tissue strain using intravascular ultrasound. AB - Spectral tissue strain (STS) is a new technique for measuring and imaging tissue strain from a set of images using intravascular ultrasound. The technique is based on the Fourier scaling property and uses the chirp z-transform (CZT) to estimate strain within the vessel walls. Some preliminary results, both in vitro and in vivo, are described. A novel display technique has also been developed for encoding radial strain and displaying the resulting colour map as an overlay on the original image. PMID- 7863566 TI - Choice of moving target for a string phantom: I. Measurement of filament backscatter characteristics. AB - Detected back-scattered Doppler signal level was measured from the following filaments: braided silk filaments, nylon and O-ring rubber. The detected signal level fell with time from the point of immersion by 45-85% for the silk filaments and by 50% for the nylon, but did not change for the O-ring rubber. For all of the silk filaments there were strong backscatter peaks at Doppler angles varying from 55-80 degrees for a transmit frequency of 4 MHz. Nylon demonstrated a large peak at 90 degrees, whereas there was no large backscatter peak present for O ring rubber. The paper concludes that the use of braided filaments for the assessment of the accuracy of Doppler estimated velocity may lead to errors if the angular backscattered peak is very strong. O-ring rubber may be suitable for the testing of Doppler-estimated velocity. PMID- 7863567 TI - Choice of moving target for a string phantom: II. On the performance testing of Doppler ultrasound systems. AB - A string phantom was used to test a duplex system using several filaments: braided silk, nylon and O-ring rubber. The estimated pulsatility index was identical for all filaments tested. Range gate registration measurements were identical for all filaments tested. Maximum velocity was underestimated in the region of a strong angular backscatter peak; this was the case for several of the braided silk filaments. This effect was not observed for O-ring rubber. The paper concluded that O-ring rubber is a suitable filament for the testing of several key Doppler quantities. Recalibration of the string phantom velocity indicator is necessary due to the large diameter of the O-ring rubber. PMID- 7863568 TI - Method for determining the reliable prediction(s) of compositions of tissue phantoms. AB - In a previous paper, we showed that mixture laws can be used to predict the compositions of tissue phantoms. Due to the variation in the performance of the mixture laws when they are applied to phantoms, however, it is difficult to determine which predictions of the composition are most reliable. In this paper, we study the causes of the variation in the performances of different sets of mixture laws, and propose a criterion for choosing a reliable predictor. The predictions selected with the proposed criterion agree very well with the known compositions of phantoms. The potential uses of the mixture methodology and the criterion to tissue characterization are discussed. PMID- 7863569 TI - The influence of internal stone structure upon the fracture behaviour of urinary calculi. AB - In vitro extracoporeal shock wave lithotripsy (ESWL) on different types of urinary calculi, in combination with microfocus x-ray and microphotography, illustrates the importance of the internal stone structure. Calculi with a rough surface layered structure (calcium oxalate monohydrate) and untextured calculi (cystine) are characterized by a low stone fragility, whereas coarse-grain calculi (calcium oxalate dihydrate, struvite), and calculi with a smooth surface layered structure (uric acid), are very fragile. Shell-like fragmentation in layered calculi, with smooth surface of the crystalline laminations, suggests that the stone matrix influenced the propagation of the shock wave energy inside the stone. PMID- 7863570 TI - In vivo detection of ultrasonically induced cavitation by a fibre-optic technique. AB - The measurement of cavitation events in tissue in vivo would greatly assist us to better understand how pulsed high energy ultrasound (PHEUS) interacts with living tissues, especially with regard to cancer therapy. To accomplish this, we designed and built a fibre-optic hydrophone. The principle was to couple the light of a laser diode into a lightfibre and to register the ultrasound induced modification of the refractive index in tissue. In this manner, the cavitation event could be quantitatively investigated both in water and in vivo. The structure of the bubble dynamic is in reasonable agreement with theoretical predictions, and in vitro measurements. With the fibre-optic set-up, the pressure signal can also be detected. PHEUS was generated by an electromagnetic source adapted from a commercial lithotripter (Lithostar Siemens). As biological tissue we used the experimental R3327-AT1 Dunning prostate tumor growing subcutaneously in the thigh of male Copenhagen rats. The lifetime of the cavitation bubble in water increased with the energy level of the ultrasonic pulse from 250 microseconds at 13 kV capacitor voltage to 750 microseconds at 21 kV, while the lifetime inside the tumor tissue in vivo increased only from 100 microseconds at 13 kV to 220 microseconds at 21 kV capacitor voltage. PMID- 7863571 TI - On Thijssen's historical review. PMID- 7863572 TI - On Nielsen's vessel diameter study. PMID- 7863573 TI - [Elimination of microscopic filamentous fungi with disinfectants]. AB - The antifungal effectivity of three single-component (Persteril, Septonex, Glutaraldehyd) and of three combined (Persteril+Septonex, Pesteril+Glutaraldehyd, Glutaraldehyd+Septonex) commercially available disinfectants was monitored by the diffuse method on five fen of the microscopic filamentous fungi Aspergillus alternata, Aspergillus niger, Mucor fragillis, Fusarium moniliforme, Penicillium glabrum. The highest antifungal activity was observed in 2% Persteril while 2% Persteril + 1% Septonex were the most effective among the combined disinfectants. M. fragilis was the most resistant strain. PMID- 7863574 TI - [Localization of endogenous developmental stages of Cryptosporidium meleagridis Slavin, 1955 (Apicomplexa: Cryptosporidiidae) in birds]. AB - Localization of endogenous developmental stages of C. meleagridis was studied on the basis of observation of 4734 preparations from individual parts (in the distance of approx. 5 cm) of the small intestine, caeca (collum caeci, corpus, apex caeci), colon, cloaca, bursa of Fabricius, respiratory organs (sinus infraorbitalis, larynx, trachea, bronchi, air sacs) using the method of scraping mucous epithelium stained according to Giemsa after fixation with methanol (as well as histologically) from 155 naturally infected 9-66 day turkeys (Meleagris gallopavo f. dom.) in four large flocks in Central Bohemia, ten 46 and 47 day chicks (Gallus gallus f. dom.) and 1-3 day chicks infected experimentally. The protozoon was detected in various stages of its development in the microvilli of the small intestine of chicks 23-39 days old in the portion of 40-80 cm from the end of the duodenum. On day 5 after infection, asexual stages were found in experimentally infected chickens as near as in 8-12 cm. All forms of endogenous developmental stages including oocysts occurred usually massively in approx. 10 cm from the site of bifurcation of the caeca (plica ileocaecalis) in the ileum and in the collum caeci. The infection was prominently less intensive in the case of mucous epithelium of the colon, in the cloaca only meronts occurred very sporadically showing various developmental stages. The findings in the bursa of Fabricius and in the organs of respiratory tract were negative. In a total of 129 turkeys examined post mortem on three farms C. meleagridis were observed, endogenous developmental stages of the protozoon were found in 55 (42.6%) cases. Asexual stages (meronts in different stages of development) were observed sporadically for the first time in 23 days old birds. Maximum of infected turkeys in which all developmental stages of C. meleagridis were localized above all in the ileum and collum caeci were 30-39 days old (out of the total number of 60 dead birds examined the infection occurred in 30, i.e. in 63.3%). C. meleagridis was found in nine out of 10 dead 46- and 47-day chicks on two farms and in five out of 98 dead 14-49 day chicks, in four out of 10 pullets 7-9 months old and in one out of 22 dead parrots (Cacatua molucensis) sent for routine examination to the State Veterinary Institute in Prague from different parts of Central Bohemia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7863575 TI - Toxoplasma gondii in muskrat (Ondatra zibethicus). AB - In 1983-1990, 256 muskrats (Ondatra zibethicus) were examined at four sites near Brno (South Moravia, Czech Republic) for the presence of the protozoan parasite Toxoplasma gondii. T. gondii infection was demonstrated in 47% of muskrats from one site with water heavily polluted with municipal wastes and 9% in muskrats from 3 sites with water slightly polluted with wastes, the difference being significant (chi 2 test, P < 0.001). PMID- 7863576 TI - [Changes in the lungs in mice caused by migration of Toxocara canis larvae]. AB - The influence of T. canis larvae migration on the lung tissue of paratenic host (inbred mice, strain C57BL6/J) was evaluated. First macroscopic manifestation was already observed on day 2 in the time of the highest larval recovery. Larvae entering the lung tissue caused numerous small extravasations. Their migration from the lungs was manifested from day 6 with an increase in the number and extent of extravasations. The lungs assumed tiger spot appearance (Fig. 1). The larval recovery was decreasing. From day 14 the expressiveness of macroscopic changes was declining. Areas of emphysema and atelectasis were observed on the lungs. The genesis and the process of elimination of extravasations were studied histologically. In the first period, the primary extravasations, caused by larvae migrating to the lung tissue (Fig. 2), were eliminated by monocytes and eosinophilic granulocytes in increasing numbers (Fig. 3). Immunohistochemically macrophages and dendritic cells were already observed in the lungs on day 1 (Fig. 4). Acid phosphatase activity was increasing from day 1 and its highest level was observed on day 84. Alkaline phosphatase activity on days 2-4 was not observed in the areas of extravasations although within the larvae themselves it was high. The extravasations of the second period (caused by larval migration from the lungs) from day 5-6 were eliminated with humoral monocytes and cells of perivascular and peribronchial tissue. Eosinophils were not active in this process. Strong exudation was observed here. The humoral part of extravasations was eliminated primarily. The cytoplasmic volume of activated cells was enlarging. Multinuclear symplasms were originated (Fig. 5). The activities of alkaline phosphatase and nonspecific esterase were increased. Macrophages and dendritic cells were still present in high numbers and from day 14 aggregations of T and B lymphocytes were observed (Fig. 6). Reparative processes were frequently observed on the blood vessels altered by the leaving larvae (Fig. 7). Changes on the lungs caused by migration of larvae always ended in functional regeneration of the lung tissue. On the other hand dead larvae stimulated proliferative forms of inflammatory reactions which led to induration (Fig. 8). PMID- 7863577 TI - Ileal lymphoma in swine. AB - Eleven cases of alimentary lymphoma affecting the ileum were observed among 26 cases of swine lymphoma detected by meat inspection in Kochi, Japan. The ileal lymphomas were located in the Peyer's patches, along with early involvement of regional lymph nodes, and showed a characteristic pattern of follicular invasion leading to diffuse growth. Following the National Cancer Institute Working Formulation, 10 neoplasms were classified as diffuse, large, noncleaved cell lymphomas and one neoplasm was a diffuse, mixed, small to large cell lymphoma. Both types of lymphoma featured numerous intermingled "starry sky" histiocytes. The lymphoma cells tended to infiltrate into the muscular layer of the ileum in an "Indian file" pattern. Two cases also showed transserosal metastasis into the abdomen and leukemic change. The lymphoma cells showed membrane positivity for alkaline phosphatase and diffuse cytoplasmic staining for acid phosphatase and non-specific esterase. Monoclonal intracytoplasmic immunoglobulins were demonstrated in nine neoplasms (IgM-lambda in seven, IgG-lambda in one, and IgG kappa in one). In the areas of follicular invasion, an attenuated network of follicular dendritic cells was visualized via an antiserum against the beta subunit of S-100 protein. Ultrastructurally, strands of dilatated rough endoplasmic reticulum and scattered or clustered dense bodies were noted. When compared with feline and human alimentary lymphoma, including Burkitt's lymphoma, the present neoplasms possessed distinctive features, such as originating in Peyer's patches, transserosal metastasis, and predominantly large B cell type with IgM-lambda type immunoglobulin expression, although some features were similar. PMID- 7863578 TI - Prognosis of canine mast cell tumors: a comparison of three methods. AB - In this study, age, sex, recurrence, metastasis, death rate, and histologic patterns were in agreement with those of previous reports on canine mast cell tumors. Histologic grading, mitotic index, chromosome nucleolar organizer regions stained with silver (AgNORs), and anti-proliferating cell nuclear antigen (PCNA) were evaluated as indicators of prognosis. Histologic grading, AgNORs estimated in 100 cells, and PCNA-labeled fraction estimated in five high power fields (HPFs) were significantly different between recurring and nonrecurring tumors. Those prognostic factors were also significantly different between tumors that metastasized and those that did not. The survival time was lower in dogs with mast cell tumors with histologic grade 3 (Patnaik's), AgNOR counts higher than 2.25, and PCNA count in five HPFs higher than 261. The significance of these factors as markers for prognosis determined by logistic regression analysis differed with the time period considered. By combining the three most significant prognostic factors in a prognostic index, three models were obtained to determine the probability of nonrecurrence at 3, 6, and 9 months after surgery. The models were accurate in the prediction of the outcome of up to 80% of mast cell tumors. The use of these models provides a less subjective means of prognosticating mast cell tumors than the use of any one component alone. PMID- 7863579 TI - Involution and cystic transformation of the thymus in the bottlenose dolphin, Tursiops truncatus. AB - The thymus glands of 10 bottlenose dolphins, Tursiops truncatus, collected along the Texas Gulf coast were examined using standard histologic and immunocytochemical methods. The thymus gland of Tursiops persists into adult life, represented by medulla and progressively thinning cortex. A network of epithelial cells, including Hassal bodies, is demonstrable using polyclonal anti cytokeratin antibody. The network condenses, with loss of lymphoid cells as involution progresses. Cysts arise within the condensed network. These cysts, found in eight of 10 animals, increase in number and size with increasing body size. Body size tends to reflect age. Thymic cysts typically have an irregular shape when small but tend to become spherical as they enlarge. They may be lined by squamous epithelium of variable thickness. Eventually, the cysts become macroscopic and filled with a colloidlike material and may largely replace the thymus, which may be identified by noncystic remnants adjacent to the cysts. PMID- 7863580 TI - Echinocytosis associated with rattlesnake envenomation in dogs. AB - A retrospective study of 28 cases of rattlesnake bites in dogs indicated an association of envenomation with echinocytosis; 25/28 dogs (89%) had echinocytosis within 24 hours of a rattlesnake bite being reported. Eighteen of the 28 dogs had marked type III echinocytosis (95-100% of mature erythrocytes affected), and seven dogs had moderate echinocytosis (15-30% of mature erythrocytes affected). The echinocytosis was transient, resolving within 48 hours of envenomation in those for which subsequent blood films were available (13/25). Hypokalemia was noted in 14 of 18 dogs for which biochemical data were available. The hypokalemia was not consistently associated with echinocytosis. The observation of echinocytosis in dogs supports a clinical diagnosis of rattlesnake envenomation. PMID- 7863581 TI - Bovine pulmonary blastomas: histomorphologic description and immunohistochemistry. AB - Three adult female dairy cattle with pulmonary blastomas were evaluated. The gross lesions at postmortem were described as multiple white circumscribed masses throughout the lungs, with pleural involvement in one cow and lymph node metastasis in the other two cows. Histologically, the tumors contained a dual population of mesenchymal and epithelial neoplastic cells. Epithelial cells formed nests, tubules, and formations resembling bronchioles of normal lung. Mesenchymal cells were spindle shaped with oval nuclei and fibrillar eosinophilic cytoplasm, were large rounded cells with multiple round nuclei and granular eosinophilic cytoplasm, or appeared blast-like, with large hyperchromatic nuclei and amphophilic cytoplasm. The tumors varied greatly in appearance from one field to another within the same tumor. Epithelial cells stained positively with anticytokeratin antibodies. Some spindle-shaped mesenchymal cells exhibited smooth muscle cell differentiation with positive staining with anti-vimentin, anti-muscle-specific actin, and anti-smooth muscle actin antibodies, whereas other rounded mesenchymal cells expressed striated muscle cell differentiation with multiple nuclei and positivity to anti-neuron-specific enolase and anti muscle-specific actin antibodies. The variable expression of the intermediate filaments and cytoplasmic enzymes indicates multiple pathways of differentiation in the pulmonary blastomas. PMID- 7863582 TI - Antigen expression in normal and neoplastic canine tissues defined by a monoclonal antibody generated against canine mesothelioma cells. AB - Monoclonal antibody (MAb) 3B5 generated against canine mesothelioma cells was applied to canine tumors and normal tissues via immunohistochemical and immunoblotting techniques to evaluate antigen binding. By use of an avidin-biotin immunoperoxidase complex (ABC) method, immunoreactivity was noted in reactive mesothelial cells and in normal tissues was observed primarily in mesothelial cell linings, endothelial cells, and smooth muscle of blood vessels and soft tissues; the reactivity was nearly equivalent in frozen or formalin-fixed, paraffin-embedded tissue sections. Use of the ABC method on formalin-fixed, paraffin-embedded tumors yielded moderate to strong cytoplasmic immunostaining of neoplastic cells in 10/11 (91%) mesotheliomas, 18/23 (78%) hemangiosarcomas, 4/10 (40%) intestinal and lung carcinomas, and < or = 20% of hemangiomas, leiomyosarcomas, leiomyomas, mammary carcinomas, and squamous cell carcinomas. No immunostaining of tumor cells was observed in fibrosarcomas, hemangiopericytomas, perianal gland carcinomas, and melanomas. Immunoblotting was performed on samples that demonstrated strong immunoreactivity with MAb 3B5 by the ABC method: mesothelioma, hemangiosarcoma, urinary bladder (smooth muscle), and lung (alveolar capillaries). These analyses showed that MAb 3B5 bound a major antigen of 78 kilodaltons (kd) and minor antigens at 56 and 54 kd in normal and neoplastic tissues. The preliminary immunohistochemical results suggest that MAb 3B5 may possess utility in diagnosis of mesotheliomas and hemangiosarcomas, discrimination of cell types in proliferative serosal lesions, and demonstration of vascularity or angiogenesis in neoplastic and inflammatory lesions. PMID- 7863583 TI - Enzyme-linked immunosorbent assay to measure serum ferritin and the relationship between serum ferritin and nonheme iron stores in cats. AB - Serum ferritin concentration correlates with tissue iron stores in humans, horses, calves, dogs, and pigs but not in rats. Because serum iron and total iron binding capacity can be affected by disorders unrelated to iron adequacy (such as hypoproteinemia, chronic infection, hemolytic anemia, hypothyroidism, and renal disease), serum ferritin is probably the most reliable indicator of total body iron stores in larger species. To test the hypothesis that serum ferritin might be correlated with tissue iron levels in cats, we developed a quantitative enzyme linked immunosorbent assay that uses two monoclonal antibodies in a sandwich arrangement to measure feline serum ferritin. The recovery of purified ferritin added to feline sera ranged from 94% to 104%; the within-assay coefficient of variability was 8.4%, and the assay-to-assay variability was 13.2%. Mean serum ferritin from 40 apparently healthy cats was 76 ng/ml (SD = 24 ng/ml). Serum ferritin concentration was significantly correlated (P < 0.001, n = 101, r = 0.365) with the nonheme iron in the liver and spleen (expressed as milligrams of iron per kilogram of body weight), as determined by Pearson product-moment correlation analysis. Because serum iron can decrease in diseases other than iron deficiency, the combination of serum iron and serum ferritin should provide sufficient evidence to differentiate anemia of chronic inflammation from anemia of iron deficiency in the cat. PMID- 7863584 TI - Fatty acid-mediated gastroprotection does not correlate with prostaglandin elevation in rats exposed to various chemical insults. AB - This study involved a comparison of activity of several long-chain fatty acids (arachidonic acid, dihomo-[gamma]-linolenic acid, linoleic acid, and oleic acid) for protection against gastric mucosal damage elicited by taurocholic acid, acidified aspirin, and ethanol in rats. Each damaging agent induced gastric mucosal lesions in the corpus. Mucosal damage was induced by all agents, and all fatty acids protected the gastric mucosa; however, ethanol and arachidonic acid were the most potent damaging and protecting agents, respectively. Maximally protective doses for prevention of taurocholic acid-induced damage by arachidonic, dihomo-[gamma]-linolenic, linoleic, and oleic acids were 50, 200, 100, and 200 mg/kg, respectively; however, 10 mg/kg arachidonic acid reduced lesion length by > 50%, whereas minimally effective doses of the other fatty acids were > or = 50 mg/kg. Similar potency differences were observed for fatty acid protection against acidified aspirin-induced gastric damage. Although all the fatty acids reduced macroscopic damage, histologic studies showed they did not totally eliminate surface mucosal damage. Microscopic analysis showed that treatment with dihomo-[gamma]-linolenic acid or oleic acid attenuated depletion of neutral and acidic glycoproteins from the mucus neck cells of the gastric mucosa in response to exposure to taurocholic acid. Despite having similar gastroprotective activity, arachidonic, dihomo-[gamma]-linolenic, linoleic, and oleic acids had very dissimilar abilities to elevate gastric mucosal E-series prostaglandins. Both arachidonic and dihomo-[gamma]-linolenic acids elevated E series prostaglandins, but arachidonic acid had 2-5-fold greater gastroprotective potency. Furthermore, oleic and linoleic acids, which had protective potency similar to that dihomo-[gamma]-linolenic acid, did not significantly elevate prostaglandins. These studies failed to demonstrate an absolute correlation between prostaglandin elevation and gastroprotection. The results of this investigation suggest that prostaglandin elevation, although associated with gastroprotection, does not appear to be the sole mechanism for fatty acid mediated protection of rat gastric mucosa. PMID- 7863585 TI - Presence of African horse sickness virus in equine tissues, as determined by in situ hybridization. AB - In a retrospective study, a negative-sense digoxigenin-labeled RNA probe, corresponding to the gene encoding nonstructural protein-1 of African horse sickness virus (AHSV) serotype 4, was applied to formalin-fixed, paraffin embedded tissue taken from horses in the terminal stages of infection with AHSV. Fifteen infected ponies and one noninfected control were studied. Ponies exhibited a range of clinical signs and lesions. Thirteen ponies were infected with serotype 4, one with serotype 1, and one with serotype 2. Ponies were monitored clinically and euthanatized when severely clinically ill. The following tissues were available for study by in situ hybridization and histopathology: lung, heart, spleen, neck muscle, and supraorbital fat. Histologically, the most striking changes were pulmonary edema and, in some, acute myocardial necrosis. In situ hybridization revealed virus distributed widely in sections of lung and heart examined, with relatively less in spleen, neck muscle, or supraorbital fat. Virus was localized to target cells with morphologic features compatible with endothelium in all organs except spleen, where it was found in both endotheliumlike cells and large mononuclear cells. PMID- 7863586 TI - Ovine lentivirus (maedi-visna virus) protein expression in sheep alveolar macrophages. AB - The expression of gag (p15, p25) and env gene products in ovine lentivirus infected cells was studied in 20 adult Texel ewes seropositive to maedi-visna virus and 10 seronegative matched controls. Bronchoalveolar lavage was performed to recover alveolar cell pools from which cytocentrifuge preparations were made. Single and double immunocytochemical techniques were applied to study viral replication and coexpression of viral markers with markers for macrophages, lymphocytes, and major histocompatibility complex (MHC) class II. Aveolar macrophages of eight of 20 infected sheep (40%) were positive for viral protein expression. The percentage of positive macrophages varied from < 1% to 12% of the total population of macrophages. Viral protein expression was not detected in lymphocytes or other cell types. A relationship between virus-replicating macrophages and differential expression of MHC class II molecules, upregulated in ovine lentivirus infection, could not be established. Pathology was evaluated in nine infected ewes. Animals with the highest levels of positive cells had moderate or severe lymphoid interstitial pneumonia. However, sheep with similar degrees of lesions had lower percentages of positive macrophages or were negative for viral protein detection. These results support the idea that a partial or even a complete loss in the restriction mechanism of maedi-visna virus in lungs can occur in some individuals. PMID- 7863587 TI - Bilateral renal carcinoma in a cat. PMID- 7863588 TI - Emphysematous-granulomatous lymphadenitis in cows. PMID- 7863589 TI - Cerebellar cortical atrophy in a kitten. PMID- 7863590 TI - Chromophilic-eosinophilic (oncocyte-like) renal cell carcinoma in a dog with nodular dermatofibrosis. PMID- 7863591 TI - Thoracic ganglioneuroblastoma in a dog. PMID- 7863592 TI - Canine angiostrongylosis: a review. AB - Angiostrongylus vasorum has been recognised as a cause of respiratory and circulatory distress among dogs in southwestern France for more than a decade, and the nematode now appears to be of increasing importance in the British Isles and Denmark. The aim of this review is to give a concise account of present knowledge of this intriguing parasitosis. PMID- 7863593 TI - Comparative evaluation of ovarian structures in cattle by palpation per rectum, ultrasonography and plasma progesterone concentration. AB - The aims of this study were to determine the relationship between the ultrasonographic determination of corpora lutea and the plasma progesterone profile of cyclic cows during an oestrous cycle, and to compare the accuracy of detection of normal and abnormal ovarian structures by ultrasonography and palpation per rectum, based on the plasma progesterone profile. The ovaries of six lactating cyclic dairy cows were scanned and blood samples were obtained three times a week for one month. There was a high correlation (r = 0.85) between the diameter of the corpus luteum and the plasma progesterone concentration, but on days -3 and -2 (oestrus = day 0) the diameter was the same as mid-luteal values but it was functionally inactive (plasma progesterone < 0.5 ng/ml). The accuracy of palpation per rectum and ultrasonography for determining the presence and age of the corpora lutea was investigated in 34 cows by using the plasma progesterone concentration and the dissection of ovaries post mortem as standards. The sensitivity, specificity and positive predictive value of palpation for identifying mid-cyclic corpora lutea were 85 per cent, 95.7 per cent and 89.5 per cent, respectively. Ultrasonography had a sensitivity of 95 per cent, a specificity of 100 per cent and a positive predictive value of 100 per cent. Twenty-nine cows were diagnosed by palpation per rectum as having either follicular or luteal cysts. During ultrasonography, an ovarian cyst was defined as a non-echogenic structure at least 5 mm in diameter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863594 TI - Iatrogenic renal obstruction in a dog. PMID- 7863595 TI - Arterial blood pressure of the African elephant (Loxodonta africana) under etorphine anaesthesia and after remobilisation with diprenorphine. PMID- 7863596 TI - Coccidial infections in neonatal Peruvian alpacas. PMID- 7863597 TI - Transport of live animals. PMID- 7863598 TI - BVD virus and pregnancy diagnosis in cattle. PMID- 7863599 TI - Feline dysautonomia in Norway. PMID- 7863600 TI - Possible familial hepatic encephalopathy in a Suffolk ewe. PMID- 7863602 TI - Manpower and education. PMID- 7863601 TI - Use of ELISAs for the diagnosis of canine atopy. PMID- 7863603 TI - Otitis externa due to Demodex canis. PMID- 7863604 TI - Norfloxacin nicotinate in the treatment of Pseudomonas aeruginosa infection in the genital tract of a bull. AB - Consecutively collected semen samples from a breeding bull were found to be contaminated with Pseudomonas aeruginosa. Palpation through the bull's scrotum revealed inflammatory changes suggestive of chronic orchiepididymitis in one testicle. For 10 months, all the bull's 13 ejaculates were discarded because the post-thaw viability was < 20%. Norfloxacin nicotinate was injected intramuscularly into the bull at 5 mg/kg daily for 7 days. Serum and semen samples were collected at 24-h intervals during the course of treatment and afterwards and were assayed for NFN concentrations. Drug concentrations in the semen, by microbiological assay, during treatment and up to 120 h after the last treatment ranged from 2.6 to 5.1 micrograms/ml, 14.2 to 43.2 times the corresponding serum drug levels. P. aeruginosa was not isolated from the semen 4 or 15 days after the last injection but was re-isolated after 32 and 64 days. A second similar course of NFN was administered and P. aeruginosa was not isolated from semen samples collected on four occasions, 6, 22, 44 and 94 days after the last treatment. PMID- 7863605 TI - Evaluation of an automated spectrophotometric assay for the determination of total sialic acid in canine serum. AB - This study validates an automated enzymatic assay using the Cobas Fara (Roche) centrifugal analyser, which offers a reliable measurement of the total sialic acid concentration in canine serum as assessed by evaluating the precision and accuracy. Data are presented on the biological variation in the total serum sialic acid concentration. Measurements of total serum sialic acid concentration appear to be useful in distinguishing dogs with neoplastic disorders from clinically healthy dogs. PMID- 7863606 TI - Serum C-reactive protein and immune responses in dogs inoculated with Bordetella bronchiseptica (phase I cells). AB - Eight Beagle dogs were inoculated intrabronchially with 5 x 10(9) live, avirulent cells of Bordetella bronchiseptica L-414 strain (phase I cells) (B. bronchiseptica) to investigate the serum levels of their C-reactive protein, the white blood cell counts, the antibody responses to B. bronchiseptica in the sera and tracheal secretions, and the effects of prednisolone given to four of the dogs on C-reactive protein (CRP), white blood cells (WBC) and immune responses. In two Beagle dogs inoculated intrabronchially with sterile physiological saline, the concentrations of CRP and the WBC counts did not increase. CRP was markedly increased one day after inoculation in the dogs inoculated with B. bronchiseptica to 385.0-720.0 micrograms/ml (mean 498 +/- 132 micrograms/ml) in the group given the B. bronchiseptica inoculation only, and to 372.0-649.0 micrograms/ml (mean 551 +/- 106 micrograms/ml) in the group treated with prednisolone following inoculation of B. bronchiseptica, as determined by an enzyme-linked immunosorbent assay (ELISA). The CRP levels were 23-95 times the pre-inoculation values, which indicated that prednisolone had no effect on the production of CRP. In the prednisolone-treated group, the WBC count increased and stayed at an increased level for approximately 12 days. An indirect fluorescent antibody test led to the detection of anti-B. bronchiseptica IgM and IgG antibodies in the sera from 5 days after B. bronchiseptica inoculation and S-IgA and IgG anti-B. bronchiseptica antibodies in the tracheal secretions on the day after the challenge exposure to B. bronchiseptica. The increase in CRP after challenge exposure to B. bronchiseptica was significantly (p < 0.05) smaller than that found after the first inoculation of B. bronchiseptica. PMID- 7863607 TI - Eucalyptus: a sustainable self-delivery molluscicide? AB - Attention is drawn to the limitations of conventional methods of controlling important trematode infections such as schistosomosis and fasciolosis. Plant molluscicides could have a role in the future control of these infections. There are, however, major problems with most plant molluscicides in that their use is labour-intensive, in many cases relatively skilled workers are required, they must be applied regularly and arable land may be required for their cultivation. Thus, little progress is to be expected until plant species with sustainable self delivery systems are identified. Eucalyptus is proposed as a likely candidate. The leaves of many species in this genus have molluscicidal properties and their intermittent fall could effect self-delivery if the trees were planted in appropriate places. Relatively little work has been carried out on this possibility and much more is necessary, especially field trials. Before field trials are started, more laboratory testing is also necessary to determine the LC50 values for different snail species and to study toxicity to non-target organisms. PMID- 7863608 TI - Caffeine clearance in the horse. AB - The pharmacokinetic properties of intravenously administered caffeine were studied in 10 horses using a commercially available automated enzyme immunoassay. The harmonic mean for the distribution half-life was 5.2 min (range 1.4-18.7). The harmonic mean for the elimination half-life was 10.18 h (range 6.82-20.92). The harmonic mean of the volume of distribution was 0.32 L/kg (range 0.22-0.53). There was no correlation between the dose of caffeine/kg body weight and the elimination half-life (Spearman's coefficient of rank correlation = 0.19). PMID- 7863609 TI - The effects of furosemide and pentoxifylline on the flow properties of equine erythrocytes: in vitro studies. AB - The effects of various concentrations of furosemide and pentoxifylline on equine RBC in vitro were evaluated to facilitate better understanding of the potential effects of these drugs on blood flow properties. Furosemide induced increased mean cell volume (MCV), increased RBC potassium concentration, increased whole blood viscosity, and decreased the RBC filtrability. These data indicate that furosemide may block the RBC membrane transport pathways resulting in potassium and water retention. The increase in size and the resultant decrease in the surface-area-to-volume ratio may have caused the impaired RBC filtrability and increased blood viscosity. Pentoxifylline improved RBC filtrability without changing the RBC size or the potassium or chloride concentrations, suggesting that pentoxifylline may increase the deformability of the RBC membrane. The study indicated that pentoxifylline has potential therapeutic applications for improving microvascular blood flow but that furosemide may have adverse effects on blood flow. PMID- 7863610 TI - Peaks of brainstem auditory evoked potentials in dogs. AB - The effects of electrode configuration and click polarity on brainstem auditory evoked potentials (BAEP) in dogs were investigated to clarify the inconsistent nomenclature for each peak. Four positive peaks (waves 1, 2, 3 and 4) before a deep negative trough and a fifth positive peak (wave 5) following the trough were the basic components of BAEP in dogs, which were easily identified regardless of recording conditions such as electrode configuration and click polarity. Additional peaks tended to be present when a noncephalic reference electrode and/or single-polarity (rarefaction or condensation) click stimuli were used. The Roman nomenclature for the individual positive peaks of BAEP in dogs is confused owing to variations in the observed waveforms among researchers, but click polarity and/or reference electrode position can explain all the previously reported variations in BAEP waveforms in dogs. When the criteria concerning 'wave V' in the guidelines of BAEP in human beings are applied to avoid further confusion of Roman nomenclature in dogs, it is recommended that the basic five positive peaks (waves 1, 2, 3, 4 and 5 as identified easily with Ai-Vertex configuration and alternating clicks) are designated as waves I, II, III, V and VI, respectively. Wave IV (wave 3b) occurs occasionally before wave V in dogs. PMID- 7863611 TI - Reflections on the pathogenesis of diseases caused by the acute avian leukosis/sarcoma viruses with special reference to avian erythroblastosis. AB - The various diseases that follow experimental infection with the acute and non acute avian oncoviruses are discussed with special reference to the pathogenesis of avian erythroblastosis. One view, based on in vitro studies, sees erythroblastosis as the product of a failure in the differentiation of virus infected stem cells to mature erythrocytes, as a result of cell 'transformation'. The results of some in vivo studies, however, point to a resemblance of the disease to a haemolytic anaemia, where cellular death is an important component. It seems probable that the disease is the result of transformation of cells of the erythroblastic series followed by the death of many of these cells due to influences that have not yet been determined. Determination of the causes of this cellular death may prove to be as important for our understanding of the problem of leukaemia as the work that has already been accomplished in explaining the causes of cell transformation. It is also suggested that the tendency of gs amino acid sequences of the avian leukosis viruses and mouse leukaemia viruses to form fusion proteins with a variety of proto-oncogenes may be part of a wider phenomenon, and that these sequences may fuse with other proteins, altering their properties. More work is required on the possibility that there is an undiscovered immunological component in the progression of the L/S diseases. PMID- 7863612 TI - A reduction in the number of directionally selective neurons extends the spatial limit for global motion perception. AB - Dynamic random-dot targets were used to study neural mechanisms underlying motion perception. Performance of cats with severely reduced numbers of cortical directionally selective neurons (reduced DS) was compared to that of normal animals. We assessed the spatial properties of the residual motion mechanism by measuring direction discriminations at various dot displacements. At small displacements, reduced DS cats' motion integration thresholds for opposite direction discrimination were nearly normal. At larger displacements, their thresholds surpassed those of normal cats and their upper displacement limit (dmax) was increased by 0.35 deg. The accuracy of direction discrimination was reduced at small displacements, but at larger displacements direction difference thresholds of reduced DS cats approached or surpassed those of normals. These data were compared to the performance of humans who showed an extension of dmax for peripherally viewed targets. The data support the hypothesis that expansion in spatial scale of the motion mechanism may contribute to extension of dmax. Additional support for this hypothesis is provided by a modified direction discriminating line-element model. The model also suggests that changes in sampling of motion mechanisms in the reduced DS system may play a role. PMID- 7863613 TI - Illusory perception of gratings stimulating a small number of neurones. AB - We studied pattern perceptions caused by drifting gratings presented monocularly in the nasal and temporal visual fields at various suprathreshold contrasts. The grating and its surround and background were matched in luminance. Small grating produced illusions and reduced perceptions. When grating area or contrast increased from a subthreshold value, the gratings were first seen as mere flashes. Then each grating was sometimes perceived as a single small bright spot or point. Next each grating was seen as a single dark or bright line. Finally the stimuli were perceived as gratings consisting of several bars. Orientation or direction of movement were perceived correctly, but velocity, colour and number of bars were often perceived as illusions. Thus, in spite of the illusions, some features of the stimuli could have allowed correct discriminations. The area and contrast limits of illusory perception depended on eccentricity. Irrespective of retinal size, the stimuli were not perceived correctly as gratings at any eccentricities when the gratings were smaller than about 1 x 1 mm in their calculated cortical area and stimulated a small constant number of retinal ganglion cells. Relations between the results and retinal aliasing, cortical columns and phase locking of neuronal oscillations are discussed. PMID- 7863614 TI - Amblyopic and peripheral vernier acuity: a test-pedestal approach. AB - This manuscript is concerned with three visual systems with degraded spatial vision: (i) anisometropic amblyopia; (ii) strabismic amblyopia; and (iii) the normal periphery. The question we ask here, is whether the poor positional acuity of each of these visual systems can be understood on the basis of reduced sensitivity to the local contrast information in the stimulus. To answer this question, we use a "test-pedestal" approach to position acuity. In the first experiment we measure our observers' thresholds for detecting both the pedestal stimuli (edges and lines) and the test or cue stimuli (lines and dipoles). This approach also provides an estimate of the size of the spatial pooling (integration) region for the local contrast cue. In experiments two and three, we measure line and edge vernier acuity as a function of contrast, and compare the losses to those found for the detection of the respective offset cues. The local contrast hypothesis predicts similar losses in vernier acuity and in "cue" detection in amblyopic or peripheral vision. Moreover, the precise form of the contrast response function can provide insights into the nature of the loss, and places constraints on the likely models for amblyopic or peripheral vision. Our results suggest that the loss in vernier acuity of our anisometropic amblyopes can be understood on the basis of the reduced local contrast sensitivity and by increased spatial pooling. In strabismic amblyopes and in the normal periphery, there appears to be an extra loss, which cannot be accounted for by either reduced local contrast sensitivity or by increased spatial pooling. Additional experiments and computational modeling suggest that the "extra" loss is not due to spatial undersampling or additive positional jitter, but rather results from positional noise at a "second" stage. PMID- 7863615 TI - Discrimination of position and contrast in amblyopic and peripheral vision. AB - Many computational models of normal vernier acuity make predictions based on the just-noticeable contrast difference. Recently, Hu, Klein and Carney [(1993) Vision Research, 33, 1241-1258] compared vernier acuity and contrast discrimination (jnd) in normal foveal viewing using cosine gratings. In the jnd stimulus the test grating was added in-phase to the (sinusoidal) pedestal, whereas in the vernier stimulus the same test grating was added with an approx. 90 deg phase shift to the pedestal. In the present experiments, we measured thresholds for discriminating changes in relative position and changes in relative contrast for abutting, horizontal cosine gratings in a group of amblyopes using the Hu et al., test-pedestal approach. The approach here is to ask whether the reduced vernier acuity of amblyopes can be understood on the basis of reduced contrast sensitivity or contrast discrimination. Our results show that (i) abutting cosine vernier acuity is strongly dependent on stimulus contrast. (ii) In both anisometropic and strabismic amblyopes, abutting cosine vernier discrimination thresholds are elevated at all contrast levels, even after accounting for reduced target visibility, or contrast discrimination. (iii) For both strabismic and anisometropic amblyopes, the vernier Weber fraction is markedly degraded, while the contrast Weber fraction is normal or nearly so. (iv) In anisometropic amblyopes the elevated vernier thresholds are consistent with the observers' reduced cutoff spatial frequency, i.e. the loss can be accounted for on the basis of a shift in spatial scale. (v) In strabismic amblyopes and in the normal periphery, there appears to be an extra loss, which can not be accounted for by either reduced contrast sensitivity and contrast discrimination or by a shift in spatial scale. (vi) This extra loss cannot be quantitatively mimicked by "undersampling" the stimulus. (vii) Surprisingly, in some strabismics, and in the periphery, at relatively high spatial frequencies, vernier thresholds appear to lose their contrast dependence, suggesting the possibility that there may be qualitative differences between the normal fovea and these degraded visual systems. (viii) This contrast saturation can be mimicked by "undersampling" the target, or by introducing strips of mean luminance between the two vernier gratings, thus mimicking a "scotoma". Taken together with the preceding paper, our results suggest that the extra loss in position acuity of strabismic amblyopes and the normal periphery may be a consequence of noise at a second stage of processing, which selectively degrades position but not contrast discrimination. PMID- 7863616 TI - Spatial scale shifts in amblyopia. AB - We used a masking paradigm to uncover the properties of the mechanisms engaged by the amblyopic visual system for vernier acuity and line detection. Line vernier and line detection thresholds were measured in the presence of one-dimensional noise masks varying in orientation, spatial frequency content or contrast. Our results reveal that in both normal and amblyopic eyes, there is a bimodal orientation tuning function for vernier acuity, i.e. vernier acuity is most strongly masked by mask orientations approx. +/- 10 deg on either side of the target lines. In contrast, in both normal and amblyopic eyes, line detection is most strongly masked when the mask and line target have the same orientation. In the normal fovea, the spatial frequency tuning is bandpass, with a peak spatial frequency of about 10 c/deg. In the amblyopic eyes, the spatial tuning is similar in specificity; however the peak is shifted to lower spatial frequencies, suggesting a shift in the scale of spatial processing of line stimuli. For all of the amblyopic eyes, the increased line detection thresholds are approximately proportional to the shift in spatial scale. In anisometropic amblyopes, the (unmasked) vernier threshold is elevated in proportion to the shift in spatial scale; however in some amblyopes with constant strabismus the shift in spatial scale is not sufficient to account for the degraded vernier acuity. The "extra" increase in vernier thresholds associated with strabismus may be a consequence of a high degree of positional uncertainty which adds noise at a stage following the combination of filter responses. PMID- 7863617 TI - Vergence compensation during binocularly- and monocularly-evoked horizontal optokinetic nystagmus in the pigmented rat. AB - During horizontal optokinetic nystagmus evoked by binocular stimulation in the rat, the slow phases are well-conjugate. The fast phases in the adducting eye are on average about 2 deg greater in amplitude than those of the abducting eye. This causes a transient convergence which is compensated for by a divergent drift within the 100 msec following the fast phase. The amplitudes of these convergence divergence components fluctuates somewhat from one fast phase to another and their relative amplitudes may differ. As a consequence differences in vergence between successive slow phases may occur. Such differences are usually of small amplitude, but may be as large as 5 deg. When optokinetic nystagmus is evoked by monocular stimulation, the slow phase velocities are different in the two eyes, giving a disjunctive component which is compensated for by a difference in the relative amplitudes and velocities of the fast phases in the two eyes. However, the divergent drift immediately following the fast phases is very similar whatever form of stimulation is employed. It is suggested that during monocularly evoked optokinetic nystagmus the oculomotor system compensates for the disjunctive component arising during the slow phases by giving a different balance to the pulses of innervation of two eyes, resulting in fast phases of different amplitude. PMID- 7863618 TI - Polarity matching in the Ternus configuration. AB - Two experiments were conducted to examine the effect of changes in the sign of element contrast on perceptions of the Ternus apparent motion display. In the first experiment, the contrast polarity of all three elements in the display were alternated from the first frame of view to the second. At short durations, this increased perceptions (relative to a control condition) of simultaneity in the display, decreased perceptions of element motion, and did not significantly affect perceptions of group motion. At long durations, this manipulation did not affect performance. In a second experiment, patterns of element polarity were manipulated to favour perceptions of either element motion or of group motion relative to a control condition in which all elements had identical contrast polarity. At a long duration, this manipulation affected perceptions of the configuration; this manipulation did not affect the appearance of the display at a short duration. Together, these results are inconsistent with the predictions of Grossberg and Rudd's [Psychological Review, 99, 78-121 (1992)] motion oriented contrast filter. However, they are consistent with a model of motion correspondence processing that includes a polarity matching constraint. PMID- 7863619 TI - A measure of closure. AB - In images of real visual scenes, contours are often fragmented by occlusion, shadows and low reflectance contrast. In order to infer shape from contour, the human visual system must selectively integrate fragments projecting from a common object while keeping fragments from different objects separate. In a previous paper we showed that contour closure has a strong influence on the speed of this process. In this paper we employ a visual search method to evaluate potential measures for the perceptual closure of fragmented shapes. We show that while certain intuitive measures are psychophysically inconsistent, a measure based on a sum of squares of the lengths of contour gaps is appropriate for both polygonal and smooth shapes in that response time can be expressed as a function of this measure. This L2 measure is shown to emphasize large gaps relative to small, and to embody a principle of perceptual regularity. PMID- 7863620 TI - The temporal dynamics of brightness filling-in. AB - The temporal dynamics of brightness filling-in were studied through neural network simulation experiments conducted under visual masking stimulus conditions. Grossberg et al. have specified a filling-in model called the Boundary Contour System/Feature Contour System (BCS/FCS). The BCS generates boundary segmentation, while the FCS fills-in surface feature within these segmentation boundaries. Simulation experiments demonstrate that the model accurately predicts that area-suppression follows a U-shaped function of forward masking and demonstrate that the psychophysical findings of Paradiso and Nakayama [(1991) Vision Research, 31, 1221-1236] which they regarded as being against the BCS/FCS model, actually support the model. PMID- 7863621 TI - Hemifield relative motion bias in adults monocularly enucleated at an early age. AB - A psychophysical study of relative motion discrimination for six subjects monocularly enucleated within 24 months of birth showed no significant difference in their thresholds for detecting relative velocity when compared with age matched control subjects. The study however highlighted a bias for the control group, age matched normals, which is consistent with a hemifield anisotropy for motion in normal observers reported by Smith and Hammond [(1986) Perception, 15, 111-117]. The bias however was found to be reversed for enucleates. This difference and individual differences reported in the Smith and Hammond study are discussed in terms of possible developmental changes which emerge when stereopsis is absent or weak. PMID- 7863622 TI - Is the spatial deficit in strabismic amblyopia due to loss of cells or an uncalibrated disarray of cells? AB - We examine two competing explanations for the spatial localization deficit in human strabismic amblyopia, namely neural undersampling and uncalibrated neural disarray. An undersampling hypothesis would predict an associated deficit for contrast discrimination for which we find no evidence in strabismic amblyopia. A neural disarray hypothesis would predict an associated deficit in the degree to which stimuli appear spatially distorted. We find evidence for such a deficit in strabismic amblyopia. We propose that the spatial deficit in strabismic amblyopia is due to a filter-based distortion which is unable to be re-calibrated by higher visual centres. PMID- 7863623 TI - Inactivation and elimination of viruses during preparation of human intravenous immunoglobulin. AB - We report here the results of our evaluation of virus inactivation during the manufacturing steps of two intravenous immunoglobulin (IGIV) preparations. Virus inactivation and/or removal by processing steps, such as ethanol fractionation and polyethylene glycol precipitation, and deliberate virucidal steps, such as solvent/detergent treatment and pasteurization, were tested on a variety of human pathogenic and experimental model viruses, including human immunodeficiency, Hepatitis C, Mumps, Vaccinia, Chikungunya, Vesicular Stomatitis, Sindbis, and ECHO viruses. All viruses were successfully inactivated and/or eliminated by the processing steps studied. In some cases, however, multiple steps were required. We conclude that the incorporation of steps deliberately designed to inactivate or remove viruses during the production of IGIV provides an extra measure of viral safety. PMID- 7863624 TI - Studies in red blood cell preservation: 9. The role of glutamine in red cell preservation. AB - Previous studies have demonstrated that an additive solution containing ammonium chloride (NH4+) and phosphate (Pi) in addition to adenine, glucose and mannitol would support red blood cell (RBC) in vitro characteristics and in vivo 24-hour viability after storage for 9 weeks. The purpose of the present study was to determine if NH4+ generated by the action of glutaminase on glutamine could be substituted for added NH4+ salts. Packed RBCs were stored with equal volumes of adenine, glucose, mannitol, and citrate containing additive solutions with 10 mM glutamine (EAS 31) or with 10 mM glutamine and either 10 (EAS 36) or 20 mM (EAS 37) Pi. One aliquot was stored with Adsol. The mean ATP levels of the RBCs stored in the glutamine plus phosphate EASs were 132 (10 mM Pi) and 144% (20 mM Pi) of the initial levels at 28 days, and at 84 days remained at 48 and 56%, respectively. The ATP levels of the RBC stored in Adsol were 105 and 25% at 28 and 84 days of storage, respectively. Percentage hemolysis and vesiculation was significantly lower (p < 0.01) for RBCs stored in glutamine and glutamine plus phosphate as compared to RBCs stored in Adsol. The levels of NH4+ were 22 to 34% higher in the EASs than in Adsol at the end of 84 days of storage, suggesting that glutamine is broken down by glutaminase to generate NH4+. The mean corpuscular volumes (MCVs) of RBCs in EASs 36 and 37 were substantially higher than in Adsol throughout the course of storage (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863625 TI - Loss of red blood cell viability associated with limited thermal inactivation of extracellular HIV-1. AB - The effects of incubation at mildly elevated temperatures on HIV-1 inactivation and in vitro red blood cell properties were investigated. Red cells (55% Hct) were leukodepleted (3 log10) by filtration, maintained at 45 or 47 degrees C for 4 or 8 h, and then stored at 4 degrees C. Hemolysis was twice that of controls after 42-day storage for samples treated for 4 h at 45 degrees C, and five times larger for samples heated at 47 degrees C. There was also a significant increase in the rate of potassium loss, an early decrease in ATP levels, and an initial drop in pH for samples treated at either temperature. Larger differences were observed for samples exposed to these elevated temperatures for 8 h. Osmotic deformability curves obtained by ektacytometry showed dramatic decreases in red cell deformability at both temperatures and for both time periods. HIV-1 inactivation in red cells treated at 45 degrees C (approximately 0.25 log10/h) was considerably less than that obtained in tissue culture medium (1-2 log10/h). Since the decrease in red cell deformability is likely to indicate reduced red cell function and survival, and the rate of HIV-1 inactivation is low, mild heat treatment is not an adequate process for viral inactivation of red cell products. PMID- 7863626 TI - In vitro evaluation of a new filter for leucocyte depletion of platelet concentrate during component preparation. AB - A newly developed filter for prestorage leucocyte depletion of platelet concentrates (PC) was studied. The filter is designed for leucocyte depletion during the preparation of the pool PC from platelet rich buffy coats. In all the leucocyte depleted PC (LD-PC) leucocyte depletion was satisfactory. 19 of 20 units of LD-PC had a leucocyte content below 3 x 10(5) per PC and 1 contained 8 x 10(5) leucocytes. The standard PC contained 2.53 x 10(8) (0.87 x 10(8)-15.3 x 10(8); n = 20) leucocytes per PC (median and range). The quality of the LD-PC was evaluated by measuring platelet activation, platelet morphology, and pre- and poststorage pH. There were no differences in any of the parameters studied. PMID- 7863627 TI - Use of 'split' plateletpheresis products for alloimmunized patients. AB - Single donor platelets obtained using the COBE Spectra were split into two halves and administered to alloimmunized patients with leukemia at two different points in time. The mean platelet yield was 6.83 x 10(11) (n = 63) with 56% of collections having yields of > 6.0 x 10(11) (i.e. twice the current AABB recommendation for an apheresis platelet transfusion). In 58 instances, the two halves were administered to the same patient 24-96 h apart. The differences in the correct increments of the split transfusions administered 24-48 h apart were not statistically significant, although there were decreased increments after 72 and 96 h of storage. In 5 instances when the CCI for first transfusion was unacceptably low, the second half was successfully transfused to another patient. This study proves it is feasible to split apheresis platelets into two transfusions, and discusses approaches to optimally use this strategy for the transfusion support of alloimmunized patients. PMID- 7863628 TI - In vitro characteristics of 'undercollected' units of whole blood in CP2D-A. AB - Blood donation volumes less than 350 ml are classified as 'undercollected' at the NSW Red Cross Blood Transfusion Service (BTS) and are discarded. This study evaluated the in vitro characteristics during storage of both undercollected units and units of acceptable volume. Thirty-two units of whole blood were each collected into 63 ml of CP2D-A, with blood volumes ranging from 180 to 456 ml. The units were stored between 4 and 6 degrees C for 35 days and in vitro measurements were performed weekly. Biochemical parameters measured included ATP, extracellular pH, total haemoglobin, haematocrit, mean cell volume, plasma sodium and potassium, plasma haemoglobin, 2,3-DPG and lactate levels. All parameters were within the BTS acceptable quality control limits for whole blood. Thus, it appears feasible to transfuse undercollected units with volumes between 180 and 350 ml. However, routine transfusion of undercollected homologous units is undesirable. In contrast, it may be preferable to transfuse an autologous unit, even if it was undercollected. The performance of in vivo survival studies would provide confirmatory data on this proposition. PMID- 7863629 TI - Transplacental IgG subclass concentrations in pregnancies at risk of haemolytic disease of the newborn. AB - The relationship of haemolytic disease of the newborn (HDN) to the transplacental passage of the four IgG subclasses was assessed at various gestational ages by comparing the maternal and fetal IgG subclass concentrations in 34 pregnancies at risk of HDN with those in 30 pregnancies not at risk. Higher maternal and fetal IgG1 levels were attained in pregnancies at risk of HDN than in pregnancies not at risk. In contrast, a slight decrease in maternal IgG2 and IgG4 levels occurred in pregnancies at risk of HDN, as compared with a slight rise in maternal IgG2 and IgG4 levels in pregnancies not at risk of HDN. Changes in fetal IgG2 and 4 concentrations in either type of pregnancy were very similar, showing only slight increases between the 19th and 34th week of gestation. A slight decrease in maternal IgG3 occurred in both types of pregnancy. In contrast, higher and fairly steady levels of fetal IgG3 were observed in fetuses not at risk of HDN throughout gestation, when compared with those in 'at risk' pregnancies. However, the statistical reliability of these results is not clear since only small numbers of samples were tested and because wide variations in IgG concentrations were observed. The IgG subclass concentrations in 50 paired maternal and cord blood samples were also measured and revealed that IgG1 levels were substantially higher in cord rather than maternal blood; cord and maternal IgG2, 3 and 4 levels, on the other hand, were fairly similar. PMID- 7863630 TI - Molecular bases of the ABO blood groups of Indians from the Brazilian Amazon region. AB - Phenotype studies of ABO blood groups in most Amerindian populations revealed the exclusive presence of group O. Since group O is the result of the absence of glycosyltransferase activity, its molecular bases may be heterogeneous. We carried out ABO blood group genotyping by analysis of DNA of 30 Indians from 2 Amazonian tribes (Yanomami and Arara), and compared the findings with other populations (Caucasians and Blacks). Two segments of the glycosyltransferase gene were amplified by PCR and digested with KpnI or AluI to detect deletion or base change at positions 258 and 700, respectively. For all subjects, the gene basis of blood group O is the deletion of a single nucleotide at position 258 of the glycosyltransferase A gene, similar to that observed in Caucasoids and Negroids. DNA sequencing of limited regions of the gene supports this conclusion. This finding does not exclude, however, that a heterogeneity of the O allele may be revealed by a more extensive analysis. PMID- 7863631 TI - A new private platelet antigen, Groa, localized on glycoprotein IIIa, involved in neonatal alloimmune thrombocytopenia. AB - The serum of a Caucasian woman who gave birth to a child with neonatal alloimmune thrombocytopenia contained antibodies directed against a platelet antigen of the newborn. There was no incompatibility for the known platelet alloantigens HPA-1 to HPA-7 or for the private or low-frequency antigens Sra and Vaa, between the platelets of the parents. However, crossmatching with the serum of the mother and the platelets of the child and the father was strongly positive, suggesting a new platelet antibody specificity. To investigate the inheritance of the 'Groa' antigen involved, the available family members were tested in the platelet immunofluorescence test (PIFT) and the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay. The Groa antigen was found to be inherited in an autosomal-codominant fashion. In the MAIPA, we localized the Groa antigen on the glycoprotein IIb/IIIa complex (alpha IIb beta 3). The GP IIb/IIIa localization was confirmed in immunoprecipitation studies. In Western blotting experiments, we further localized the Groa antigen on the GP IIIa (beta 3) subunit of the GP IIb/IIIa complex. Until now we have tested approximately 400 unrelated donors. None of these appeared to be positive for the Groa antigen, suggesting a phenotype frequency in the Dutch population of less than 0.01. PMID- 7863632 TI - Characteristics of anti-A and anti-B in black Zimbabweans. AB - Sera from young, black, group 0 Zimbabwean blood donors were screened for anti-A and anti-B haemolysins. Nearly one fifth of the sera were found to be strongly haemolytic for either A or B cells or both. Some of the sera were titrated for agglutination in saline before and after treatment with dithiothreitol. Serum dilutions beyond the endpoint of agglutination were further tested by the indirect antiglobulin technique using specific anti-IgM and anti-IgG sera. More than 60% of the strongly lytic sera had high titres of IgG (> or = 64). The IgM and IgG concentrations both of anti-A and anti-B were correlated and these levels were in turn correlated with haemolytic activity. PMID- 7863633 TI - Soluble HLA class I and beta-2-microglobulin plasma concentrations during interferon treatment of chronic myelogenous leukemia. AB - Soluble class I molecules (sHLA-ABC) were measured by an enzyme-linked immunosorbent assay (ELISA) in plasma samples of 13 patients with chronic-phase Ph1-positive chronic myelogenous leukemia (CML). The patients were treated once daily with interferon (IFN) s.c. at a dosage of 4 x 10(6) IU/m2 IFN-alpha-2b or in combination with 50 micrograms IFN-gamma. Measurements were performed before 2, 4, 6, 8, 24, 48, and 72 h after the start of treatment and thereafter every 2 4 weeks. Baseline sHLA-ABC levels were within normal limits (mean 22.1 +/- 8.8 mg/l). An initial decrease of sHLA-ABC (mean 3.2 +/- 2.7 mg/l) was seen in all patients during the first 2-8 h of IFN treatment. Thereafter, sHLA-ABC levels increased steadily reaching maximum values within 2-5 weeks. The overall increase was 12.7 +/- 12.4 mg/l. During the following 2-4 months of IFN treatment sHLA-ABC decreased to near baseline levels in 12 of 13 patients. No difference was detected between IFN-alpha and IFN-alpha plus IFN-gamma treatment. beta 2 Microglobulin values were measured in 8 patients and were found to be correlated to sHLA-ABC concentrations (r = 0.48). PMID- 7863634 TI - Effect of different intravenous immunoglobulin regimens on hemorrhages, platelet numbers and volume in a child with Wiskott-Aldrich syndrome. PMID- 7863635 TI - An intravascular hemolytic transfusion reaction due to anti-'Mi(a)' in Taiwan. PMID- 7863636 TI - HTLV-1 infection in a thalassemic patient from Apulia (southern Italy) PMID- 7863637 TI - Blood transfusion practice in gynaecology and obstetrics. Retrospective audit. PMID- 7863638 TI - Increases in anti-Rh(D) titre following pregnancy. PMID- 7863639 TI - Detection of G to A missense mutation of Lewis-negative gene by PCR on genomic DNA. PMID- 7863640 TI - The treatment of gastroesophageal reflux disease. AB - Gastroesophageal reflux disease (GERD) is a common disorder which may result in esophageal ulcers, erosions, strictures and motility disorders if it is not treated promptly. Physician assessment of risk factors and symptoms is essential for accurate diagnosis and determination of appropriate treatment. Mild cases of GERD can be treated with lifestyle modifications and antacid/alginic acid therapy. Moderate and severe GERD can be treated with histamine-2-receptor antagonists (H2RAs) or omeprazole. The H2RAs require split-dosing, at least twice daily, and higher than peptic ulcer disease treatment doses, while omeprazole 20 to 40 mg may be used. Prokinetic agents and sucralfate have been used as adjunctive treatments, however, conflicting data exist about their efficacy. Maintenance therapy is usually required to avoid disease recurrence; either H2RAs or omeprazole may be prescribed. PMID- 7863641 TI - Exercise induced anaphylaxis: one more cause for syncope. AB - Syncope is a very common problem. Young people who exercise regularly are considered to be in "good health, " when they complain of passing out during exercise, it must be treated as a serious condition. Exercise Induced Anaphylaxis (EIA) is a well known cause for syncope in sports medicine and allergy literature. A patient's history is critical in making this diagnosis. With the current exercise boom, internists and family practitioners need to be even more aware of EIA when patients complain of syncope with physical activity. PMID- 7863642 TI - Battle of the Bulge: a remembrance. PMID- 7863643 TI - Managed care = veterinary care. PMID- 7863644 TI - Endotracheal suctioning of the newborn piglet. AB - Suctioning of the endotracheal tube (ET) is a necessary procedure to remove secretions and debris that naturally accumulate over time. Endotracheal suctioning protocols often call for the injection of small (< or = 0.5 ml) amounts of normal saline down the ET tube just prior to commencing the suctioning procedure. Comparisons of room temperature and body temperature normal saline injectate protocols and their impact on arterial blood gas parameters and heart rate alterations prior to, during, and following the endotracheal suctioning procedure were conducted. Eleven newborn Yorkshire piglets less than 24 hours of age were randomly exposed to both the room temperature (RT) and body temperature (BT) normal saline suctioning protocols. The analysis and interpretation of the results revealed that the RT normal saline injectate caused a greater decline in heart rate and greater alterations in arterial blood gas parameters than did the BT normal saline injectate. PMID- 7863645 TI - Measurement of heart rate variability. AB - Heart rate variability (HRV) is a measure of autonomic nervous system balance/imbalance. Measurement and analysis of HRV can be classified into time domain analysis and frequency domain analysis. Time domain analysis is a general measure of autonomic nervous system balance and is based on altered versions of the measurement of the standard deviation of heart period, defined in terms of the sinus R-R intervals over time. There are six commonly used time domain measurements: SDANN, 24-hr SD, SD, RMSSD, RR50, and % RR50. Frequency domain analysis uses either autoregressive or fast Fourier transform techniques to delineate parasympathetic (high-frequency components) from sympathetic (low frequency components) of autonomic control. This study explores the clinical applications of HRV with respect to respiratory sinus arrhythmia, exercise, mortality, sudden cardiac arrest, myocardial infarction, and congestive heart failure. PMID- 7863646 TI - Spatial patterns of fiber types in atrophied skeletal muscle. AB - This study examined the spatial distributions of different fiber types in the soleus muscle of control rats and in rats subjected to hindlimb unloading for 28 days. The frequencies with which muscle fibers of one type were adjacent to each other and to fibers of other types were tabulated and compared to expectations generated from Monte Carlo simulations. In the normal rat, there is a tendency for Type I fibers to avoid adjacency with each other, a tendency that persisted in the hindlimb-suspended group, despite the substantial shrinkage in size of Type I fibers. We conclude that this treatment, unlike neurogenic pathologies, does not cause any remodeling of the adjacency relations of fibers. PMID- 7863647 TI - A perspective on biological research in nursing. PMID- 7863648 TI - Effect of supplemental dietary calcium on the development of DOCA-salt hypertension in weanling rats. AB - This study characterizes the response to dietary calcium in DOCA-salt hypertension. Body weight, systolic blood pressure, and total serum calcium levels were compared among normotensive control rats, DOCA-salt hypertensive rats treated with calcium carbonate (CaCO3) augmentation, and DOCA-salt hypertensive rats without supplementary dietary calcium. Dietary calcium augmentation prevented the rise of blood pressure that is normally produced by DOCA-salt. Attenuation in systolic blood pressure was independent of weight loss or total serum calcium and may be linked to alterations in calcium homeostasis that are seen in both human and experimental hypertension. Thus this study provides important data that may assist in further explicating the role that alterations in calcium homeostasis play in DOCA-salt hypertension. Further, these data may also be important in the identification of a nonpharmacological intervention for testing in humans. PMID- 7863649 TI - The effect of nursing interventions on transcutaneous oxygen and carbon dioxide tensions. AB - The objectives for this study were to (a) establish reference values for transcutaneous oxygen tension (PtcO2) and carbon dioxide tension (PtcCO2) in response to three common patient events (a nurse-administered bed bath, passive range-of-motion exercises, and turning from side to side), and (b) determine if these physiological parameters vary according to the order in which the interventions are administered. A convenience sample of 30 healthy men and women were randomly assigned to one of three treatment groups, which designated the order in which the interventions were administered. Instrumentation included a Novametrix Model 840 transcutaneous monitor, a Dinamap BP monitor, a BoMed NCCOM3 cardiovascular monitor, and YSI 44008 thermistors. Analysis of ambient temperature at baseline revealed that the room was significantly cooler for men than for women. Analysis of covariance revealed no significant difference between men and women, except at baseline. The mean PtcO2 for each activity, as well as the post-activity period, was significantly higher than at baseline. There was a significant interaction between gender and activity for PtcO2 and PtcCO2. For both men and women, the mean changes in PtcCO2 were statistically significant but clinically insignificant. The order in which interventions were administered did not have a significant effect on either PtcO2 or PtcCO2. The results suggest that the physical activity associated with nursing interventions may significantly improve oxygen levels in the skin by stimulating overall cutaneous circulation. PMID- 7863650 TI - Gastric motility in rats with varying ovarian hormone status. AB - Gastrointestinal (GI) symptoms suggestive of altered motility vary with menstrual cycle phase and menopause, but the effects of ovarian hormones on gastric motility have not been described. Basal and stimulated gastric motility were studied in male and female rats that were ovariectomized and implanted with continuous-release progesterone and/or estrogen pellets. Following 26 days of hormone treatment, rats were implanted with a gastric tension transducer. Contractile activity was recorded, then thyrotropin-releasing hormone (TRH) or saline was injected intracisternally and motility was monitored. An index was calculated based on frequency and amplitude; response to TRH was expressed as percentage of the basal index. Basal contraction frequency was highest in the estrogen and estrogen+progesterone groups. Hormone treatment significantly affected the TRH-stimulated motility index; TRH induced increased motility in all groups, with larger, more sustained responses in vehicle, progesterone, and male groups. Results demonstrate the ovarian hormone modulation of basal and stimulated gastric motility. Such modulation may contribute to changes in GI symptoms with altering ovarian hormone state. PMID- 7863651 TI - Respiratory responses to unsupported arm lifts paced during expiration. AB - Unsupported arm exercise endurance is reduced in both normal subjects and patients with chronic obstructive pulmonary disease in association with an increase in dyspnea and alterations in the pattern of respiratory muscle recruitment. Some report greater difficulty carrying out arm activity paced during the expiratory phase of respiration rather than during inspiration. The purpose of this study was to determine the effect of unsupported arm exercise lifts paced in phase with expiration (EUAL) on (a) diaphragm recruitment measured as the electromyographic amplitude (EMG-DI), (b) the pattern of thoracoabdominal motion measured with inductive plethysmography, and (c) the sensation of dyspnea measured with a 100 mm visual analog scale. Data were collected from 18 normal adult subjects at baseline and during EUAL. When compared with rest, EUAL resulted in significant increases in mean inspiratory and expiratory diaphragm EMG amplitudes, dyssynchronous thoracoabdominal motion, and dyspnea intensity. These changes in diaphragm recruitment and thoracoabdominal motion may in part explain reports of increased dyspnea intensity with unsupported arm exercise. PMID- 7863652 TI - Early interventions in the management of acute uncomplicated myocardial infarction. AB - The demonstration that the vast majority of acute transmural myocardial infarctions are caused by an occlusive thrombus in the coronary artery, together with the concept that myocardium can be salvaged for a period of time after the onset of such occlusion, has heralded a new era of management of this disorder. This involves an aggressive interventional approach aimed at restoring coronary artery patency early while decreasing myocardial oxygen demands. Abundant data show that coronary flow can be reestablished using either intravenous chemical thrombolytic agents (tissue-type plasminogen activator and streptokinase), percutaneous transluminal coronary angioplasty, or coronary artery bypass grafting. Conjunctive aspirin or heparin therapy (or both) is effective in maintaining vessel patency once perfusion is restored. Myocardial oxygen demand can be reduced, where feasible, by pharmacotherapy and control of the patient's associated pain and anxiety. The beta-adrenergic blockers and nitrates are particularly suitable in this regard, and angiotensin-converting enzyme inhibitors favorably affect infarct expansion and ventricular remodeling. With such an approach, infarct size can be reduced, leading to improved left ventricular function--the prime determinant of morbidity and mortality in patients with acute infarction. The in-hospital mortality has fallen from about 30% three decades ago to less than 8% in many coronary care units. PMID- 7863653 TI - Herniography in symptomatic patients following inguinal hernia repair. AB - Patients with symptoms at the site of a previous inguinal hernia repair may constitute a diagnostic dilemma. The usefulness of herniography in the assessment of these patients was evaluated at 54 symptomatic sites in 46 subjects. Ten persistent or recurrent hernias were shown by herniography, only 2 of which were definitely detected on physical examination. The herniogram was normal at 44 sites, of which, on physical examination, 5 were equivocal and 1 was diagnosed as a definite hernia. On the unoperated-on or asymptomatic side, a total of 14 hernias were shown herniographically. Of these hernias, 8 were not detected on physical examination. Herniography was found to be more sensitive than physical examination in detecting hernias at the symptomatic, previously operated-on sites, as well as at the unoperated-on or asymptomatic sites. When a herniogram provides corroborative evidence that hernia has not recurred, the need for reexploration may be eliminated. PMID- 7863654 TI - How well do older persons tolerate moderate altitude? AB - We studied the physiologic and clinical responses to moderate altitude in 97 older men and women (aged 59 to 83 years) over 5 days in Vail, Colorado, at an elevation of 2,500 m (8,200 ft). The incidence of acute mountain sickness was 16%, which is slightly lower than that reported for younger persons. The occurrence of symptoms of acute mountain sickness did not parallel arterial oxygen saturation or spirometric or blood pressure measurements. Chronic diseases were present in percentages typical for ambulatory elderly persons: 19 (20%) had coronary artery disease, 33 (34%) had hypertension, and 9 (9%) had lung disease. Despite this, no adverse signs or symptoms occurred in our subjects during their stay at this altitude. Our findings suggest that persons with preexisting, generally asymptomatic, cardiovascular or pulmonary disease can safely visit moderate altitudes. PMID- 7863655 TI - Dizzy patients. Diagnosis and treatment. AB - This discussion was selected from the weekly Grand Rounds in the Department of Medicine, University of Washington School of Medicine, Seattle. Taken from a transcription, it has been edited by Jonathan Drachman, MD, Chief Medical Resident; Henry Rosen, MD, Professor and Associate Chair; and Paul Ramsey, MD, Professor and Chair of the Department of Medicine. PMID- 7863657 TI - New muscle relaxants. AB - The Council on Scientific Affairs of the California Medical Association presents the following epitomes of progress in anesthesiology. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and clinical importance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of progress in medicine, whether in their own field of special interest or another. The epitomes included here were selected by the Advisory Panel to the Section on Anesthesiology of the California Medical Association, and the summaries were prepared under the direction of Dr Jackson and the panel. PMID- 7863658 TI - Preparing children for anesthesia and surgery. PMID- 7863656 TI - Pulmonary surfactant therapy. AB - Surfactant replacement therapy is now an integral part of the care of neonates since several clinical trials of natural surfactant extracts and synthetic preparations have shown efficacy in the treatment of infants with hyaline membrane disease. In these studies, early treatment with exogenous surfactant substantially reduced mortality and the incidence of air leak, although it did not appear to reduce the incidence of other complications, in particular bronchopulmonary dysplasia. Early reports of exogenous surfactant therapy in patients with the adult respiratory distress syndrome, although promising, remain limited in number. More research is needed to improve on current modes of therapy and to investigate the possible role of surfactant in other lung diseases of both newborns and adults. PMID- 7863659 TI - Inhaled nitric oxide. PMID- 7863660 TI - Operative hysteroscopy intravascular absorption syndrome. PMID- 7863661 TI - Desflurane--a new inhalation anesthetic. PMID- 7863662 TI - Intraspinal narcotics for obstetric analgesia. PMID- 7863663 TI - New advances in airway management. PMID- 7863664 TI - Cactus thorn embedded in the cartilaginous proximal tibia. PMID- 7863665 TI - Mixed bacterial meningitis in a 4-year-old girl. PMID- 7863666 TI - Reactive arthritis following Clostridium difficile colitis. PMID- 7863667 TI - Vasculitis possibly confined to the small and large intestine. PMID- 7863668 TI - al-Kindi--physician, philosopher, and savant seven centuries before the Renaissance. PMID- 7863669 TI - Can the specialist be a generalist? PMID- 7863670 TI - Radiologic case. Right hilar mass. Squamous cell carcinoma of the esophagus with hilar metastasis. PMID- 7863671 TI - Dizziness in primary care. PMID- 7863672 TI - Surfactant replacement therapy--room for improvement. PMID- 7863673 TI - Echocardiography. PMID- 7863674 TI - A New Year's resolution for the new era's revolution: leading change through a changing lead. PMID- 7863675 TI - EVP report: the view from here. At the heart of medicine lies the heart of humanity. PMID- 7863676 TI - AIDS: sonography of hyperechoic renal pyramids in renal candidiasis. AB - A 13-month-old patient with autoimmune deficiency syndrome had renal candidiasis. An abnormal renal sonographic pattern of hyperechoic renal pyramids was demonstrated. This abnormal sonographic finding should suggest renal candidiasis in an immune suppressed child. In the normal kidney of children, the pyramids are hypoechoic. This pattern has not been noted in previous publications. We report this case. PMID- 7863677 TI - Screening men for domestic violence in your medical practice. PMID- 7863678 TI - Health education delivery by Wisconsin veterinarians. AB - Established methods of health promotion for the general population are not as effective with rural populations, in part because conventional health education delivery systems may not penetrate isolated rural areas. In particular, the self reliant behaviors of farmers make them less likely to seek traditional forms of health care, including health promotional activity. Yet farmers place a great deal of trust in their veterinarian and highly rate veterinarian integrity. Wisconsin veterinarians expressed an interest in the health of their human clients as well as the health of the animals in their care. An education demonstration project was developed to determine farmers' acceptance of veterinarians delivering human health information to their workplace (farms). Thirteen veterinarians who provide services in one north central Wisconsin county delivered skin cancer and sun protection information to farmers as part of their routine herd health checks. Participating farmers reported this to be an acceptable way to receive information about human health issues. This novel method of education delivery may be an effective means to disseminate human health information to difficult-to-reach rural populations. PMID- 7863679 TI - Stark realities: coping with federal and state self-referral paranoia. PMID- 7863680 TI - Epidemiology of osteoarthritis. PMID- 7863681 TI - PIC Wisconsin: continued commitment to physicians. PMID- 7863682 TI - Mini internship report: creating new and stronger allies. PMID- 7863683 TI - [Intracoronary interventions in the early infarct period]. AB - Despite that intravenous thrombolysis can be regarded as the routine treatment of acute myocardial infarction, alternative or additive interventional procedures in some situations may be well indicated. Primary dilatation without preceding thrombolysis, introduced by G. Hartzler, has shown significantly better results in mortality, re-infarction rate, reduction of coronary stenoses, and improvement of ejection fraction compared to thrombolysis in several randomized studies. The procedure, however, is based on expensive logistics and very experienced operators. In patients with evident failure of lysis, large infarctions, depressed left ventricular function, and cardiogenic shock, rescue-PTCA is indicated. If it is performed early this intervention shows good acute and late results. The elective dilatation of residual stenoses after successfull thrombolysis is performed only in selected cases. Its main indication is proven ischemia within the first days and weeks after onset of infarction. Early cardiac surgery is performed in patients with cardiogenic shock, papillary or septum rupture, and with cardiac tamponade. Good results can also be expected in main stem stenoses and severe multivessel diseases. The optimal time of surgery, however, is still controversial. The Task Force of the International Society and Federation of Cardiology (IFSC) and the World Health Organization (WHO) has worked out recommendations for intracoronary maneuvers in various situations of the acute phase of myocardial infarction. With thoughtful consideration of indications these additional procedures in the hands of experienced teams play an important role in the acute treatment of this severe disease. PMID- 7863684 TI - [The value of magnesium in intensive care medicine]. AB - In the management of severely ill patients it has been suggested that magnesium might protect the heart muscle and prevent lift-threatening irregularities of heart rhythm. 1) Cardiac arrhythmias: The mechanism of action of magnesium in monomorphic ventricular tachycardia is not known. Magnesium does not affect the effective refractory period of ventricular structures. It alters the inward rectifying potassium channel in experimental animal models. Though magnesium may exhibit negative inotropic effects in animal studies, an increase of the cardiac index during ventricular tachycardia could be documented in recent investigations. The application of magnesium is usually well tolerated. Magnesium (i.v.) is indicated in Torsade de pointes tachycardia Digitalis-induced cardiac arrhythmias Monomorphic ventricular tachycardia (efficacy ca. 30%) Multifocal atrial tachyarrhythmias. 2) Myocardial infarction: In the past, several trials of intravenous infusions of magnesium have indicated a considerable mortality reduction following myocardial infarction. More recently, the LIMIT-2 (Leicester Intravenous Magnesium Intervention Trial) of a 24-h magnesium infusion in about 2000 patients indicated a benefit of about 25%. Now, the ISIS-4 (International Study of Infarct Survival)-trial has tested magnesium in 58,000 patients. In ISIS 4 there was no evidence of a beneficial effect of magnesium on mortality--neither in all patients nor in any particular type of patient. Overall, there was no beneficial effect on morbidity. According to these data, there seems only a limited role for magnesium in the routine treatment of cardiac infarction patients. IN CONCLUSION: Intravenous magnesium can terminate Torsade de pointes tachycardia and, in selected patients, monomorphic ventricular tachycardia regardless of the serum magnesium concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863685 TI - [Is prolonging life the ultimate goal?]. AB - If values are projections of human interests, prolongation of life cannot always be the highest value. Since the criterion of treatment decisions such cases must be the value of life for the individual concerned, besides "passive" euthanasia- which is widely accepted--also (indirectly and--in extreme cases--also directly) "active" euthanasia may be considered. The radical difference between this position and "euthanasia" in the "Third Reich" consists in the fact that, in our case, only the wishes and interests of the patient can be relevant, and not the decisions of authorities or considerations of expenses. Concerning the problem of just distribution of scarce medical resources, which will become more of on issue in the near future, simple solutions (e.g., a general age-limit for expensive therapy) are not helpful. More promising are considerations which start from the idea of a hypothetical health insurance, on the lines of J. Rawls' "Theory of justice". PMID- 7863686 TI - [Cost/benefit relations in heart transplantation]. AB - The expanding role of cardiac transplantation as well as mechanical and antiarrhythmic bridging requires a critical reflection of the economic impact of these therapeutic modalities. Based on assumptions from the pertinent literature, cardiac transplantation requires costs of about 55,000 DM per year of life gained by the procedure. Even if a maximum social and professional reintegration percentage of about 60% is assumed, it does not seem possible to perform the procedure without additional costs to the health care system. The consequences of this are the following: 1) Cardiac transplantation should only be performed by centers experienced in all aspects of terminal heart failure care including a heart failure program, high-risk conventional surgery program, mechanical and antiarrhythmia bridging program, and qualified post transplant care program. 2) In order to evaluate potentially cost-saving therapeutic strategies in cardiac transplantation, multicenter trials have to be conducted which require a continuous scientific working group and research data organization based on the consensus of all participating transplant centers. 3) An improved professional reintegration program is necessary. 4) The ethical foundation for offering cardiac replacement to patients, namely, the responsibility for the individual person's well-being, has to be emphasized by physicians active in the field. 5) The society as a whole, not the group of physicians active in the field, has to debate and decide on how many resources should be spent in this field of health care. 6) Since potential cardiac transplant recipients are, to a large extent, recruited from patients suffering from coronary artery disease, it is essential to incorporate a primary preventive perspective into this high-technology field of medicine. PMID- 7863687 TI - [Quality assurance in echocardiography]. AB - Echocardiography is the most important noninvasive diagnostic tool for the cardiologist. More than 617.000 two-dimensional echo examinations and 425.000 color coded Doppler analyses were performed in 1992 in the Federal Republic of Germany in private practice. Based on a questionnaire, more than 60% of the departments of cardiology perform echocardiograms in more than 3000 pts per year, and the amount of TEE examinations is in the range 5-15% of the total annual echo performance rate. In more than 80% of all examinations color coded Doppler is used. With regard to the guidelines for performing the different echo modalities the German recommendations are stringent in comparison with the international standard. Due to the fact that an echocardiographic examination is strongly investigator dependent, the primary goal of quality management should be focused on training. PMID- 7863688 TI - [Cost/benefit relations: evaluation of inpatient and ambulatory rehabilitation]. AB - Three different forms of rehabilitation in patients after myocardial infarction are discussed on the basis of cost-effectiveness: 1) outpatient rehabilitation as performed in North America and other developed countries, 2) inpatient rehabilitation in Germany, and 3) outpatient rehabilitation in Germany. Parameters compared are mortality, coronary risk factor profile, and return to work. A metaanalysis of international studies on outpatient rehabilitation demonstrated a significant reduction of total and cardiovascular mortality. Similar data are not available for inpatient rehabilitation in Germany. However, data of 6 years of outpatient rehabilitation as performed in the "Heidelberg Study" demonstrate a continuous significant improvement in coronary risk factor profile and cardiopulmonary fitness. On the other hand, 4 weeks of inpatient rehabilitation exhibited only short-term and no long-lasting effects (4 years) on coronary risk factor profile. The economic benefit can be based on return to work, which is only marginally affected by rehabilitation in the USA, where more than 80% of the patients are back to work 6 months after myocardial infarction. In Germany, about 5 months after myocardial infarction 50% of the patients are retired, despite 4-6 weeks inpatient rehabilitation; i.e., the patients which are back to work can be assumed to be less than 50%. The costs of 8 weeks outpatient rehabilitation in North America has been calculated to be 804 DM per patient, 4 weeks of inpatient rehabilitation amounts to about 5320-5600 DM, and 1 year ambulatory treatment in the "Heidelberg Study" accounts for 2270 DM per patient. It can be concluded: outpatient rehabilitation as performed in North America has been shown to significantly reduce total and cardiovascular mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863689 TI - [Cost/benefit relations: therapy of hypertension]. AB - Antihypertensive therapy improves the long-term prognosis of patients with mild to moderate essential hypertension and is able to prevent complications. This is also true for the elderly patient with hypertension. A considerable percentage of patients with mild essential hypertension can be adequately treated without drugs. If drug treatment is required, diuretics, beta-blockers, calcium antagonists, and ACE-inhibitors are the agents of first choice. For the individual patient, the appropriate drug should be chosen on the basis of efficacy, lack of side-effects, and depending upon additional diseases, such as cardiac failure, coronary heart disease and renal failure. Only if these selection criteria are fulfilled should differences in prices of the various groups of antihypertensive agents be considered. PMID- 7863690 TI - [Benefits and costs of early detection and treatment of hypercholesterolemia]. AB - Hypercholesterolemia is the epidemiologically most relevant parameter of hyperlipoproteinemia 1) for its high prevalence of almost 40% > = 250 mg/dl in the adult German population (30-65 years) and 2) because of a relative risk of 3 and more for coronary heart disease. An estimate of the cost to benefit relation of early diagnosis and therapy requires epidemiological, clinical, and economic analysis. A synopsis of the present scientific discussion leads to more restricted recommendations for treatment than before, i.e., limited to males aged 40-65, of high cardiovascular risk and cholesterol of at least > = 250 mg/dl. An even more conservative approach especially with regard to screening programs is not justified yet. However, careful monitoring of forthcoming trials and meta analyses is mandated. The costs for an indicated cholesterol-lowering medication are not extreme, but there are large differences between different drugs on the German market. Overtreatment of the aged population occurs together with undertreatment of hypercholesterolemic men of medium age. PMID- 7863691 TI - [Valvular diseases of the right heart]. AB - Recently, the development of diagnostic and operative interventional techniques has contributed to the successful treatment of congenital valve lesions of the right heart. The clinical picture, diagnostic approaches, and therapeutic outcome are presented. In pulmonic valve stenosis the fusion of leaflets is most common. Stenosis severity corresponds to the intensity of the systolic murmur. Pressure gradients can be quantitated by Dopplersonography. Balloon valvuloplasty is the method of choice for treatment. Residual gradients (24-36 mmHg) are not significantly different from surgical results. In Tetralogy of Fallot the ventricular outflow tract obstruction and a subaortic septal defect are most characteristic, both of which can be visualized by echocardiography. Cyanosis and the pulmonary systolic murmur are typical findings. Complications due to hypoxemia are reduced by corrective surgery in early childhood. Arrhythmias and ventricular dysfunction may complicate the long-term prognosis. Pulmonary insufficiency mostly results from surgical relief of stenoses. It can be quantitated by densitometry and MNR. Even severe pulmonary insufficiency is well tolerated for decades; on the long-term its prognosis remains uncertain. In Ebstein's anomaly the leaflet attachment of the tricuspid valve is displaced into the right ventricle, which is best diagnosed by echocardiography. Symptomatology ranges from heart failure (infancy) to a systolic murmur only (childhood). Plastic recontruction of the tricuspid valve has become technically feasible. PMID- 7863692 TI - [Arrhythmogenic right ventricular disease]. AB - In patients with arrhythmogenic right ventricular disease (ARVD), life threatening ventricular tachyarrhythmias and sudden cardiac death mostly occur in adolescence, or in young adults before the age of 40. In the right ventricle, progressive fibrolipomatous replacement of the ventricular myocardium is pathognomonic. In severe cases progressive congestive right heart failure can develop although mild forms are extremely difficult to recognized. In most cases the disease can be diagnosed only by elaborate investigation. Right ventricular cineangiography, myocardial biopsy, MRI, and electrophysiological investigation are the most important diagnostic procedures. If the disease is diagnosed in an early stage the risk of life-threatening arrhythmias can be reduced by carefully selected antiarrhythmic therapy. PMID- 7863693 TI - [Pathophysiology of pulmonary hypertension]. AB - Severe pulmonary hypertension has a poor prognosis and is complicated to treat. It is caused by states of hypoxia, thromboembolism, chronic inflammation, pulmonary venous congestion and/or hypercirculation. In the course of some days up to many years, remodelling of the pulmonary vasculature may occur. Morphologic characteristics of the remodelling process have extensively been described, while the underlying cellular and molecular mechanisms remain largely unknown. Increasing knowledge of the features of pulmonary vasoconstriction and vascular remodelling, will, however, improve the options for future therapy. PMID- 7863694 TI - [Surgical treatment of thromboembolism-induced pulmonary hypertension]. AB - Non-resolved chronic pulmonary thromboembolism is a frequent cause of pulmonary hypertension. In long-standing disease hypertension is progressive due to intimal and medial changes in the perfused vessels. Non-resolution of thromboemboli is often associated with underlying coagulopathies; the presence of a lupus anticoagulant may pose a significant problem in the peri-operative management of these patients. Pulmonary thrombendarterectomy presents an efficient option of treatment which is feasible in the majority of patients. By means of pulmonary angiography and computed tomography operability is verified by the often difficult recognition of thromboembolic changes in the central pulmonary arteries. Patients with solely peripheral thromboembolic changes or primary pulmonary hypertension must be excluded. In presence of significant exertional dyspnea and/or pulmonary pressure elevation surgery is indicated. Mortality is high and mainly related to unrelieved pulmonary hypertension or pulmonary complications; pulmonary reperfusion edema, respiratory failure or pneumonia and sepsis. In all survivors the reduction of pulmonary hypertension is highly significant and persistent. Thromboembolic pulmonary hypertension may be treated curatively in most patients by thrombendarterectomy. Correct selection of surgical candidates is mandatory, and the patients should preferably be diagnosed and undergo surgery in an early stage of their disease. PMID- 7863695 TI - [Lung transplantation in pulmonary hypertension]. AB - Medical therapy for pulmonary hypertension is very limited and surgical interventions can only be performed in cases with acute or chronic pulmonary embolism. Secondary pulmonary hypertension of other origin (Eisenmengers' Syndrome) as well as primary pulmonary hypertension can only be treated with lung transplantation. In selected cases, three different techniques are available, heart-lung transplantation (HLTx), single, and double lung transplantation (SLTx; DLTx). The indication for any of these operations has to be made on an individual basis, and the degree of pulmonary hypertension and right ventricular failure have to be encountered. Also, correctability of the underlying congenital disorder in Eisenmenger Syndromes has to be taken into account. In principle, combined heart-lung transplantation will allow for the best results. Due to the restricted number of donor organs, SLTx and DLTx are performed in increasing numbers. SLTx for pulmonary hypertension, however, is characterized by a high number of early (reperfusion injury) and late complications (ventilation perfusion-mismatch). Following lung transplantation in pulmonary hypertension, 1- and 5-year survival rates of 70 and 60% can be expected, respectively. Which type of transplantation will ultimately prove to be the best therapy for pulmonary hypertension has not yet been defined. PMID- 7863696 TI - [Quality assurance in cardiology: ergometry/long-term ECG]. AB - Besides routine Ecg, exercise testing and Holter monitoring represent the most frequently applied non invasive cardiological examinations, performed not only within the hospital and by practising cardiologists, but most frequently by general practitioners as well as internists. Recommendations for standards of these methods have been published by Working Groups of the European Society of Cardiology as well as the American College of Cardiology and the American Heart Association. Based on these recommendations, this manuscript gives a survey about the prerequisites (equipment, staff), indications, "lege artis"-procedure, as well as interpretation of the results of both techniques. These recommendations can be used to set certain standards; furthermore, possibilities for the control of these quality standards are outlined. PMID- 7863697 TI - [Quality assurance in cardiology: nuclear medicine]. AB - Quality control as regards nuclear medicine heart studies refers to two areas: methodological quality control clinical quality control. Methodological correct realization of nuclear medicine heart studies is the first prerequisite for validity of the results. The term "myocardial scintigraphy" summarizes several different procedures. Concerning clinical routine, myocardial scintigraphy stands for imaging of microcirculation and scars using Tl-201-chloride or Tc-99m-MIBI, additionally for metabolic assessment of myocardial viability with F-18-FDG. Today, planar myocardial scintigraphy has been replaced by tomographic techniques (SPECT, PET). Methodological procedures for quality control concerning technical equipment and radiopharmaca are based on the new "guidelines for radiation exposure in medicine" of 1993. Clinical quality control in myocardial scintigraphy covers, in particular, the correct selection of indications: proof/exclusion of coronary artery disease (depending on prevalence) specific questions before interventional therapy (myocardial ischemia, myocardial viability) follow-up and therapy control. Selection of the procedure for myocardial scintigraphy depends on the clinical question. However, different methodological strategies are under discussion. Adequate preparation of the patient and realization of the investigation (withdrawal of medication, selection of type and intensity of stress) are prerequisites for valid results. Interpretation has to consider that myocardial scintigraphy represents different parameters than, for example, coronary morphology. False positive as well as false negative results can occur due to methodological and biological causes. Optimization of methodological and clinical quality control in nuclear medicine heart studies requires a close and competent co-operation of cardiologists and nuclear medicine physicians. PMID- 7863698 TI - [Quality assurance in cardiology: invasive electrophysiologic studies]. AB - Quality assurance in invasive cardiac electrophysiology is of growing interest, also for cost-benefit-analysis. It can be achieved by following guidelines first published by the German Cardiac Society in 1985, which will soon be presented in revised form. Of major importance is proper education of the cardiologist who will be responsible for the indication, the enforcement, and the interpretation of the results. Furthermore, clear documentation is required in order to allow supervision, e.g., via spot checks by external experts. PMID- 7863699 TI - [Quality management in the heart catheterization laboratory]. AB - Quality management within the catheterization laboratory includes the quality control, the heart catheterization technique and the policy. Quality management is critical in the heart catheterization laboratory. Dedication of all members of the lab and computer personnel ensures high patient satisfaction. A continued quality improvement program is patient-orientated and requires good planning. One of the main emphasis in the catheterization lab is standardization which includes the patient preparation, the procedure itself, and the management. It is supported by teamwork including the economic aspect of prompt delivery of material and avoidance of complications. A continuous circle of treatment planes, performance, and check is regarded as the Deming cycle and leads to continuous improvement of quality. Important are both the avoidance and detection of complications. The reasons for any such have to be evaluated. It is recommended to follow the zero mistake hypothesis of Crosby, which means quality control by the lab supervisor, a quality consciousness, a quality measurement and quality improvement, as well as using a day to day quality improvement and to teach quality control. In Germany a quality control questionnaire was administered in an analysis of the current structure, function, and results of catheterization labs. Most important was the analysis of complications. The data were based on diagnostic catheterization in 1992, which included 140668 catheterizations in 83 laboratories. Thus, a mean of 1030 heart catheterizations was performed in each lab. In the mean, 200 catheterizations were performed by each doctor. In 19% of the labs digital imaging was exclusively performed. Major complications occurred with ventricular fibrillation in 0.36% (range 0.75%), resuscitation 0.18% (0.43%), persistent cerebrovascular accident 0.08% (0.24%), myocardial infarcts 0.19% (0.59%), aortic dissection 0.05% (0.22%). Mortality was 0.03% (0.08%). In heart catheterization laboratories quality management is one of the major goals for the future work. Only the continued improvement of quality and very good quality management ensure patient safety. Quality is the sum of technique and consciousness. PMID- 7863700 TI - [Principles, possibilities and limits of gene therapy]. AB - The term gene therapy summarizes the attempts to correct inherited or acquired genetic defects by molecular genetic techniques. The manipulation of somatic cells differs in fundamental ethical aspects from that of germ cells. Some technical aspects of gene transfer, integration, and expression are discussed as well as the conditions set by the nature of the defect to be corrected. Adenosine deaminase deficiency is used as an example to demonstrate current approaches and their limitations. PMID- 7863701 TI - [Minimizing radiation exposure for the patient and staff]. AB - Therapeutic interventional methods in cardiology increase radiation exposure of patients and staff to a much higher extent than any other radiological examination. Reasons for this fact and ways to reduce the exposure are presented. PMID- 7863702 TI - [Quality assurance in PTCA]. AB - The special need for quality assurance in PTCA results from increasing numbers of procedures, which are due to the prevalence of disease, high primary success rates, progressive simplicity of the basic procedure, but guaranteed financing in Germany. Quality assurance programs first have to take into account the procedural quality, which includes preparation, performance, result, and also overall appropriateness (the indication) of PTCA, and secondly, the structural quality, including personnel, organization, cardiac laboratory facilities and technical equipment. In spite of numerous publications addressing special issues relating to PTCA, these items have been largely neglected in research, and it is uncertain which parameters and methods are meaningful for the improvement of clinical quality and effectiveness. Two examples for general and for internal quality control are demonstrated. In a first extensive quality assurance project of the ALKK study group, all PTCA procedures of a complete group of hospitals are prospectively registered on an intention-to-treat basis, data are controlled by visiting monitors, and appropriateness is examined in a representative sample of procedures by evaluating complete patient files. As an example for an internal quality control system a software program (CLAIM, cardiac laboratory angiography investigation management) is presented. The program yields clinical data but also investigator-related parameters such as fluoroscopy time, investigation time, contrast use, balloon consumption, etc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863703 TI - [Quality assurance in interventional electrophysiology (ablation, automatic defibrillators)]. AB - The rapid development of interventional electrophysiology during the recent years has lead to an increasing number of procedures and a wide-spread use of these techniques. Interventional electrophysiology includes catheter ablation of supraventricular and ventricular tachycardias and implantation of cardioverter defibrillators. Measures for quality assurance aim at improving the quality of training in clinical electrophysiology as well as at giving recommendations for the personnel needed. The specific recommendations for implantation of defibrillators include the qualification of the personnel and technical prerequisites as well as recommendations for accepted indications, probable indications as well as for no indications. For catheter ablation, specific recommendations have been given as well which include the technical and personnel requirements. The presently available recommendations and guidelines help that the various elements of quality assurance obtain increasing attention and are going to affect the quality of results. PMID- 7863704 TI - [Monitoring ischemia with new markers]. AB - The measurement of cardiac enzymes is critical for the diagnosis of acute myocardial infarction. Cardiac enzymes, however, are by no means ideal marker molecules, primarily due to their non-specific tissue distribution and low concentration in cardiomyocytes. Many limitations of cardiac enzymes can be overcome by the measurement of cardiospecific troponin T or I with immunological techniques. In the evaluation of new diagnostic methods it is important to define the purpose of marker molecule measurement, i.e., monitoring of definite myocardial infarction or establishing the proper diagnosis in patients with suspected myocardial infarction. For monitoring of success of reperfusion therapy and for the detection of reocclusion short-lived perfusion markers with rapid appearance in circulation such as myoglobin, fatty acid binding protein or glycogenisophosphorylase BB are preferable. For proper diagnosis in patients with suspected acute myocardial infarction test systems with high sensitivity and specificity are needed due to the low prevalence of disease in the patients tested. Troponin T determinations are particularly useful in this group of patients. With troponin T determinations it could be shown that some patients so far classified as having unstable angina do in fact have microinfarction. These data indicate the need for re-definition of diagnostic criteria of acute myocardial infarction. PMID- 7863705 TI - [Different therapeutic regimens in thrombolysis of acute myocardial infarct]. AB - An early, complete, and sustained patency of the infarct related artery achieved by thrombolytic therapy reduces mortality in patients with acute myocardial infarction. In the ISIS-3-study there was no difference in mortality between t PA, APSAC, and streptokinase. In contrast, in the GUSTO-trial, a "front-loaded" regimen of t-PA (100 mg/90 min) lead to a reduced inhospital mortality compared to streptokinase. This was most likely due to the higher early patency-rate of the infarct-related artery after the front-loaded t-PA. The search for new, more effective, thrombolytic regimens lead to a double-bolus injection of t-PA (2 x 50 mg) which revealed high early patency rates (> 80% TIMI-3 after 90 min). R-PA, a new recombinant plasminogen activator with a prolonged half-life, given as double bolus (2 x 10 MU), also produced high patency rates after 90 min without an increased incidence of reocclusions. Acetylsalicylic acid should be given routinely in every thrombolytic therapy. An anticoagulation with heparin seems to improve the efficacy of the more fibrin-specific thrombolytics t-PA, r-PA, and pro-urokinase. In dose-finding studies the specific thrombin inhibitor hirudin has been shown to significantly reduce reocclusions and reinfarctions compared to heparin. An "optimal thrombolysis" most likely can only be achieved by a thrombolytic agent with a very high early patency combined with an effective adjunctive therapy with platelet aggregation- and thrombin-inhibition. PMID- 7863706 TI - [Therapy of cardiogenic shock]. AB - Cardiogenic shock is a syndrome of different etiologies resulting in the inability of the heart to provide adequate O2 delivery to peripheral organs and tissues with or without signs of severe pulmonary congestion or pulmonary edema. Clarification of the underlying etiologies is essential for prognosis and therapy. Depending on the various etiologies, the therapeutic procedure may be totally different. Furthermore, it is decisive to differentiate between an acute shock (e.g., acute myocardial infarction) and the development of a cardiogenic shock state on the basis of preexisting chronic congestive heart failure (e.g., congestive cardiomyopathy). Whenever possible the underlying disease should be treated causally (e.g., PTCA or thrombolytic therapy in AM, lysis in acute pulmonary embolism) in addition to symptomatic pharmacologic treatment with vasodilators and/or inodilators. In myogenic cardiogenic shock, the treatment with inotropic drugs (with and without vasodilatory potency) and, if necessary, in combination with additional vasodilators may be life-saving. At present, there is no alternative to catecholamines in the acute state with apparent hemodynamic instability. Catecholamines still represent the initial first line treatment. A Swan-Ganz catheter is mandatory in such situations. In view of the rapid beta 1 receptor down-regulation induced by endogenous catecholamines, long-term administration of exogenous catecholamines (adrenalin, dopamine, dobutamine), seems essentially problematic, since these compounds intensify and accelerate this process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863707 TI - [Research in gene therapy--its status in Germany]. AB - Progress in mammalian molecular biology and in the analysis of the human genome has allowed to identify the causes of an increasing number of human diseases in recent years. Newly developed gene transfer techniques were reason to implement new therapeutic concepts. By means of viral vectors or other transfer vehicles genes can be introduced into cells of the human body in order to replace a deficient function (in inherited diseases) or to play a role in defending the body (against cancer or, in the cardiovascular field, eventually by preventing restenosis). Despite considerable achievements of current DNA transfer technologies it seems premature to qualify gene therapy already as a new medical practice. The development in Germany is characterized by a late start in this field of research. The number of projects is correspondingly small. However, it may be expected that newly initiated governmental support of gene therapy research will lead to an expansion of the activities in this area. PMID- 7863708 TI - [Mechanical cardiac assist systems in intensive care]. AB - The indications for the use of mechanical cardiac assist-devices are sudden death, cardiogenic shock, severe coronary ischemia and high-risk PTCA. Among the cardiac assist-devices, currently available for cardiologists and cardiac surgeons, are the Intraaortal Balloon Pump (IABP), the implantable turbine-pump, the percutaneous cardiopulmonary support (PCPS), centrifugal pumps which are connected via a thoracotomy and intra- and extrathoracic total artificial hearts. It is easy to position the IABP, which can be continuously used over the course of several days. In the case of cardiogenic shock, the pump should be implanted as soon as possible, in order to facilitate revascularisation procedure in a patient with ischemic heart disease. By this procedures the survival rate of ischemic cardiogenic shock has been raised from 20% to 60%. However, the IABP does not prove supportive in the case of an MI without shock or in high-risk PTCA. The implantable turbine pump (Hemopump TM) is available in 3 configurations, ranging in external size from 14 F to 26 F. Of these, only the 14 F pumps can be implanted percutaneously by a Seldinger technique, whereas the bigger pumps require arteriotomy or thoracotomy for placement. The pump-rates of these systems reach from 2.0 l/min to 4.5 l/min. These pumps are used in high risk PTCA as well as CABG-surgery without cardiopulmonary support, but are still currently in a test phase. However, at this point, it is still too early to finally evaluate the clinical importance of these systems. The percutaneous cardiopulmonary support (PCPS) has a major advantage over all other assist device systems, as it completely replaces the circulation. Therefore, PCPS is especially indicated in cardiac arrest, because it can be inserted very quickly, even without having to interrupt resuscitation. A second indication is high-risk PTCA, where it can be used also as a stand-by system. A study with 801 patients, investigating the use of this system in high-risk PTCA, resulted in a hospital mortality of 6.9%. In therapy-resistant circulatory arrest, approximately 30% of patients could be saved with this system, provided that there is a very quick access to it, as there is for example in the cardiac cath lab. Centrifugal pumps, which are inserted via a thoracotomy, and artificial hearts have become very important and are now used routinely in cardiac surgery to support patients, who have developed therapy-refractory heart failure, and in transplantation-surgery as "bridging to transplant". These systems, however, bear the complications of hemorrhage and thromboembolism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7863709 TI - [More movement in cardiology!]. PMID- 7863710 TI - [Changes in antithrombin III, prothrombin fragment 1 + 2 and thrombin antithrombin III complex following implantation of a coronary Palmaz-Schatz stent]. AB - To detect changes in the clotting parameters antithrombin III (AT III), prothrombin-fragment 1 + 2 (F 1 + 2) and thrombin-antithrombin-III-complex (TAT) after implantation of Palmaz Schatz stents, coagulation was monitored at standardized time points in 35 patients for 10 days. All patients were anticoagulated using a combination of heparin, phenprocoumon, and acetyl salicylic acid. Heparin therapy was guided by APTT levels (normal range 25-35 s), which were still within the therapeutic range (median 49.6 s (25%/75% percentiles 41.6/54.4) on day 10. Simultaneous oral anticoagulation was found to be effective on day 8 on average (INR median 2.24 (1.93/2.50)). The AT III activity dropped significantly (p < 0.0001) after a heparin loading dose of 15,000 IU during stenting. As the heparin dose was reduced on the following days, AT III levels increased significantly (p < 0.0001) during the observation time. There was a highly significant (p < 0.001) negative correlation between AT III and heparin levels. On days 4 and 5 F 1 + 2 values were significantly (p < 0.001 and p < 0.05) higher than on the day of stenting (median 1.07 (0.90/1.31) 1.13 nmol/l and 1.06 (0.85/1.23) nmol/l vs. 0.97 (0.69/1.15) nmol/l) and dropped during anticoagulation. F 1 + 2 levels showed a significant negative correlation (p < 0.0005) with APTT values. TAT values showed no significant changes during the observation period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863711 TI - [Pseudo-stenosis caused by vessel wall invagination during interventional treatment of 2 coronary vessels in a patient]. AB - We report on a 59-year-old man who underwent a combined procedure of directional coronary atherectomy (DCA) and PTCA of significant lesions of the right coronary artery (RCA) and the left circumflex artery (LCX). Already after positioning of a standard guide wire in the right coronary artery a new excentric "pseudo stenosis" was observed in the proximal part of the right coronary artery. Since the patient remained symptom free, a 7F DCA catheter was introduced to the stenotic area in the mid RCA, which led to an extension of the narrowing, involving the total segment proximal to the DCA catheter. Directional coronary atherectomy was performed without complications. Removal of the catheter, after successful DCA, and administration of intracoronary nitroglycerin did not relieve the proximal narrowing, which disappeared spontaneously after the guide wire was pulled out. During PTCA of the left circumflex using a standard guide wire and a 3.0 mm Monorail balloon catheter, a similar tight narrowing of the origin of the LCX was observed, which could also not be influenced by vasodilator drugs, but relieved after wire removal. Until now, this phenomenon has only been described for the right coronary artery. The reason underlying intimal folding is a shifting of the intimal layer against the medial layer of the vessel wall. Our observation firstly describes this phenomenon of "pseudo narrowing" in two different vessels in one patient. We, like other authors before, recommend that interventional therapy of these pseudo-lesions should be avoided. PMID- 7863712 TI - [The role of anti-tachycardia stimulation in patients with 3rd-generation defibrillators]. AB - The most effective antitachycardia pacing mode (ATP) is still a matter of debate. Randomized prospective testing of 5 different ATP modes was performed in 82 patients (pts) prior to and after cardioverter defibrillator (ICD) implantation. The 5 ATP modes included 3-4 stimulation attempts with 4-10 adaptive scanning burst pulses. Adaptive burst coupling interval was 75% in mode A, 81% in mode B, 69% in mode C, 72% in mode D, and 88% in mode E. Auto-decremental scanning within bursts was 8 ms in modi A, B, and C, and 10 ms in modus E; autodecremental scanning between bursts was 8 ms in modi B and C, and 10 ms in modus D. During the pre-op electrophysiologic study (EP), termination (TR) of induced ventricular tachycardia (VT) was possible in 69% and by pre-discharge EP in 53%. Acceleration (AC) rates were 16% pre-op and 32% post-op (p = ns). There were no significant differences in TR or AC between modes A-E. During a mean follow-up of 18 +/- 4 (< 1-41) months, 3182 arrhythmia episodes (AE) occurred: 344 AE (11%) were terminated by primary ICD shocks and ATP was attempted in 2838 AE (89%) and was successful in 2576 AE (91%). AC occurred in 87 AE (3%) and ATP was without effect in 175 AE (6%). Our data show that ATP is helpful in patients with third generation ICDs and is very effective during follow-up. However, there is no ideal ATP-mode visible in the present study. PMID- 7863713 TI - [Implantable cardioverter/defibrillators with endocardial electrode systems: long term stability of the defibrillator's effectiveness]. AB - The vast majority of cardioverter/defibrillator implantations is performed with non-thoracotomy lead systems. The temporal stability of defibrillation energy requirements is well established for epicardial defibrillation lead systems, but not for non-thoracotomy lead systems. The defibrillation energy requirements were reevaluated in 30 patients, 13 months after implantation of a cardioverter/defibrillator with a non-thoracotomy lead system. The study patients group consisted of 4 females and 26 males; mean age 60.1 +/- 10.5 years; mean left ventricular ejection fraction was 32.2 +/- 6.2%. Coronary artery disease was the underlying heart disease in 12 patients, dilated cardiomyopathy in 15 patients, and artificial valve replacement in 3 patients. There was no clinical progression in the underlying heart disease between defibrillator implantation and control measurements; left ventricular ejection fraction was unchanged (32.2 +/- 6.2 vs. 32.3 +/- 6.4%); no changes occurred regarding patients' clinical status. In 27/30 patients the defibrillation threshold at defibrillator implantation could be reconfirmed at control measurements. The mean defibrillation energy/requirements at implantation (14.4 +/- 4.8 Joules) were unchanged compared to control measurements (14.8 +/- 4.6 Joules). A temporal stability of defibrillation energy requirements could be established for the monophasic (n = 15; 18.0 +/- 4 vs. 18.1 +/- 3.4 Joules) as well as for the biphasic waveform (n = 15; 11.1 +/- 3.4 vs. 11.5 +/- 2.9 Joules). The results of intraoperative defibrillation thresholds measurements are predictive for chronic defibrillation energy requirements in patients with non-thoracotomy lead systems. PMID- 7863714 TI - [Recurrent stenosis following coronary angioplasty. Clinical, cell biological and molecular aspects]. AB - Percutaneous transluminal coronary angioplasty by balloon dilatation (PTCA) has proved to be the standard procedure for non-operative removal of coronary artery stenoses. Since the initial description and application by Andreas Gruntzig, the results of this procedure are excellent with an acute success rate of 90-96%, a rate of severe acute complications of 1% and less, and a procedure-related death rate below 1%, mainly due to considerable technical improvements and greater experience of the interventional cardiologists. On the other hand, the restenosis rate following PTCA could not be significantly lowered. In recent years a number of alternative angioplasty devices has been developed aimed at-among other indications-reducing the restenosis rate following PTCA by a "less traumatic" vessel angioplasty. These include radiofrequency angioplasty (RFCA), high frequency rotational angioplasty (HFRCA), excimer-laser angioplasty (ELCA), directional atherectomy (DCA), as well as implantation of intravascular stents. Based on more or less extensive experiences from the literature, the aim at lowering the recurrency rate by the latter procedures has been missed, despite the fact that particularly ELCA and HFRCA were used to reduce stenoses in lesions unsuitable for balloon catheter dilatation. There is a trend of lowering the recurrence rate with the implantation of coronary stents. The benefit of this procedure, however, is at the expense of an increased rate of acute stent thrombosis and by local acute bleeding problems quite often requiring surgical repair. The cellular biological mechanisms following balloon angioplasty are only partially understood. Among these are a number of interactive processes like cell adhesion, coagulation, vascular contraction, cell migration, cell proliferation, and synthesis of extracellular matrix. In this respect, migration and proliferation of smooth muscle cells represent a key process for the development of restenosis. In addition, endothelial denudation represents a stimulus for migration and proliferation of smooth muscle cells. Rapid and efficient reendothelialization may counteract this process. Recent progress of modern biology has provided new concepts and methodological tools for the molecular analysis of vascular remodeling. It has been shown that specialized cellular functions such as proliferation, migration, and production of extracellular matrix can be mediated by growth factors such as platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) or transforming growth factor-beta (TGF-beta).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7863715 TI - [Bacterial endocarditis of the transvenous lead of an implantable cardioverter/defibrillator]. AB - A 27-year-old patient carrying a transvenous ICD developed infective endocarditis more than 1 year after surgery. Staphylococcus aureus was isolated from blood cultures. A transesophageal echocardiogram revealed a mobile vegetation on a thrombus attached to the ICD lead in the right atrium. The ICD lead was removed by right anterolateral thoracotomy. This raises the issue of the risk of thrombus formation in patients with intravenous ICD leads and the associated susceptibility to infective endocarditis. PMID- 7863716 TI - [Comparative studies of hemodynamics under prostacyclin and nifedipine in patients with Eisenmenger syndrome]. AB - In 10 patients 4-20 years of age with obstructive pulmonary vascular disease after Eisenmenger reaction pulmonary arterial and aortic pressure, pulmonary and systemic flow (Qp, Qs), and pulmonary and systemic vascular resistance (Rp, Rs) were determined before and during stepwise increasing doses of prostacyclin and nifedipine. Prostacyclin caused a significant decrease of pulmonary and systemic vascular resistance and a significant decrease of pressures in the aorta and the pulmonary artery, whereas no significant changes of hemodynamics were realized following nifedipine. The individual hemodynamic changes during prostacyclin were favorable in only two patients who demonstrated a marked decrease of Rp with no substantial change of Rs resulting in an increase in arterial oxygen saturation. In the other patients prostacyclin resulted in an adverse effect with a decrease of Rs exceeding that of Rp in 5 patients, a paradoxical increase of Rp in 1 patient, and a critical decrease of Qs with respective low central venous blood oxygen saturation and consequently low arterial oxygen saturation caused by a small right-to-left shunt in 2 patients. Nifedipine did not bring about a significant general change of hemodynamic parameters. The individual control showed no effect in 5 patients, an unfavorable effect by a decrease of Rs exceeding that of Rp in 2 patients, and a favorable net effect in only 3 patients, induced in 1 patient only after a very high dosage of nifedipine and leading to a certain increase of arterial oxygen saturation in only 1 other patient. From our results a beneficial effect of nifedipine in an average dosage on the hemodynamics of patients with Eisenmenger syndrome cannot be recognized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863717 TI - [Balloon dilatation of the pulmonary valve within the first 40 days of life in critical valvular pulmonary stenosis, Fallot's tetralogy and following surgical or interventional high-frequency opening of pulmonary atresia]. AB - A balloon-valvuloplasty of the pulmonary valve (BVP) was carried out in 14 patients within the first 40 days of life. Six infants had a critical valvular pulmonary stenosis with intact ventricular septum (group S), 5 infants had a pulmonary atresia with intact ventricular septum (group A), and 3 infants had a tetralogy of Fallot (group F). In 4 of the 5 patients of group A the BVP was preceded by operative opening of the pulmonary valve. In one case radiofrequency perforation of the valve during the first diagnostic cardiac catheterization could be carried out successfully. The average value of the ratio of the balloon diameter to the diameter of the pulmonary valve was 1.31 +/- 0.20. The systolic pressure in the right ventricle dropped 51 mm Hg (from 106 +/- 32 mm Hg to 55 +/- 9 mm Hg) in group S and 33 mm Hg (from 101 +/- 27 mm Hg to 68 +/- 19 mm Hg) in group A. In group F the arterial oxygen saturation increased 15%, however the pressure of the right ventricle was, after the BVP, slightly higher than before. The average residual gradients after BVP were in group S 28 +/- 15 mm Hg, in group A 34 +/- 12 mm Hg and in group F 48 +/- 18 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863718 TI - [Abnormal origin of the right coronary artery from the pulmonary artery. A case report]. AB - An asymptomatic 4-year-old girl with anomalous origin of the right coronary artery from the pulmonary trunk is reported. Echocardiography showed overall dilated coronary arteries with anomalous course of the right coronary artery anterior to the aortic root. During heart catheterization the catheter could be moved from the proximal pulmonary trunk into the aberrant right coronary artery. Because of the coronary-pulmonary steal phenomenon corrective surgery with aortic reimplantation of the right coronary artery is recommended even in asymptomatic patients. PMID- 7863719 TI - Chromosomal speciation and folliculogenesis in the semisterile interspecific hybrids of the varying lemmings, genus Dicrostonyx. AB - Karyotypes of Dicrostonyx torquatus torquatus and D. vinogradovi that are very similar phenotypically differ at least by 13-14 chromosomal rearrangements including centric and tandem fusions, fissions and paracentric inversion. In their male hybrid F1 spermatogenesis is arrested on early pre-meiotic stages, the female hybrids are semisterile. Histological investigation of ovaries has demonstrated reduced number of follicles, higher percentage of atretic follicles and an acceleration of folliculogenesis in hybrids as compared with the parental forms. As a result of the acceleration, the number of mature follicles and ovulations is not significantly diminished in the hybrid females, and their semisterility is caused, to a great extent, by high prenatal loss which most likely arises from the chromosomal imbalance in F2 hybrids. Thus, the mechanism suggested by the concept of chromosomal speciation is active, but not alone in forming reproductive isolation between twin species of the varying lemming. PMID- 7863720 TI - [The reciprocal training of Drosophila individuals in a group situation by the trial-and-error method]. AB - In the group situation, fruit flies try to avoid conflicts in which they kick each others. At first they attempt to escape from each other thus increasing run frequency as compared with control solitary individuals, but shortly terminate runs in order to prevent collisions. Motoric activity and conflict frequency during encounters are high in such situations. From the very beginning, probability of transition from activity to direct contact is higher than that from rest to contact or from preening to contact. Therefore, during the first 5 minutes a fly learns to increase interval between runs using the trial-and-error method. Besides abrupt decreasing of number of collisions and activity of flies in group as compared with control, operant training leads to formation of passive aggregations, because closely situated flies avoid to display activity. A new behavior reaction is developed, as well, namely immobile fly initiate preventive touches by legs. Such training is adaptive because in the natural aggregations of flies on fermented fruits it increases aggressive activity decreasing thus raising efficiency of feeding on a common substrate. PMID- 7863721 TI - Malaria vaccine: the end of the tunnel? PMID- 7863722 TI - Comparative study of chewable pyrantel pamoate: should standards for chewable tablets be revised? AB - Chewable pyrantel pamoate tablets were administered to children randomly assigned to three treatment groups. Individuals in each group were instructed either to swallow whole, to chew and swallow, or to swallow previously pulverized tablets. With respect to Ascaris, results of posttreatment stool examinations indicated no differences in cure rates and egg reduction rates between the different modes of treatment. However, for both hookworm and Trichuris, mean egg counts increased for both swallow and chew groups, but decreased in the pulverized group. In addition to the highest egg reduction rates, the most parasitological cures were also seen in the pulverized group for these two worms. The status of standards for chewable tablets is discussed. Until the standards are changed it is recommended that all chewable tablets be crushed before swallowing. PMID- 7863723 TI - Prevalence of hookworm infection, anaemia and faecal blood loss among the Yupno people of Papua New Guinea. AB - The present report describes a study of hookworm infection, anaemia and the presence of blood in stool among the inhabitants of the Yupno area in Madang Province, Papua New Guinea. The study group comprised 588 persons of all age groups. A second group of 45 patients attending the Madang General Hospital, in the provincial capital on the coast, was used for comparison. In the Yupno area, 59% of the subjects were infected with hookworm; in the coastal group the infection rate was 82%, which was significantly higher. There is therefore a moderate prevalence of hookworm infection in the Yupno area, which does not impair the health of the population to any great extent. In both places there was a clear increase in the infection rate between the group of children 1-5 years old and the older groups. The mean blood haemoglobin level was 15.1 g/dl among the Yupno, which was significantly higher than that of the second group (10.7 g/dl). There was a significant negative linear correlation between the intensity of hookworm infection and blood haemoglobin level. The Colo-Rectal-Test for blood in stool was used on samples from 145 persons in the Yupno and from 43 in the coastal group. The test gave positive results in 17% of the cases without worm infection. In infected persons, the Colo-Rectal-Test gave an increasing rate of positive results as the parasite burden increased: 24% for subjects with low levels of infection, and 57% and 67% for moderate and high levels, respectively. The Colo-Rectal-Test is therefore a simple method for the detection of faecal blood loss in populations with a high prevalence of hookworm infection. However, it is not useful as an instrument for general screening for hookworm infections. PMID- 7863724 TI - An algorithm to estimate age in women during their childbearing years. AB - Estimating age in women living in rural areas of Papua New Guinea can be inaccurate and subject to observer bias. Parity is often used, but this means that survey results cannot be used to examine the effect of childbearing on nutrition. We describe a method for estimating age in women independent of their parity developed during studies of women's health in the Wosera Subdistrict of Papua New Guinea. The tool, appropriately modified, may be useful to others conducting surveys requiring an estimate of maternal age. PMID- 7863725 TI - Surgery, surgical pathology and HIV infection: lessons learned in Zambia. AB - HIV (human immunodeficiency virus) infection is prevalent in many areas of sub Saharan Africa. Seropositivity rates reach 10-15% in urban adults, 21% in critically ill adults and 30% in surgical inpatients aged 21-40 years. AIDS (acquired immune deficiency syndrome) is a multisystem disease which presents to the surgeon with a wide range of pathologies including Kaposi's sarcoma, lymphadenopathy and sepsis. The more common sites for sepsis are the female genital tract, anorectum, pleural cavity, soft tissues (necrotizing fasciitis) and bone and joints. To prevent iatrogenic HIV infection more use should be made of autologous blood. Occupational exposure to HIV infection can be minimized by double-gloving, protecting the eyes when operating and ensuring that theatre gowns are waterproof. The risk of HIV infection from a needlestick injury is 0.4%. Although contact with blood during a surgical procedure is common, the risk is lower than for a hollow needlestick injury. PMID- 7863726 TI - Childhood epilepsy in Papua New Guinea. AB - A prospective study of 40 children with epilepsy was carried out between June 1990 and August 1991 at Port Moresby General Hospital. Half of the children had yet to start school. Significant features in their past medical histories were acute meningitis (38%), tuberculous meningitis (10%), febrile convulsions (10%) and head trauma (5%). Most cases had grand mal epilepsy (80%). The majority of the children with epilepsy (90%) were treated with a single drug, which was usually phenobarbitone. 22% had received more than one drug, but not simultaneously. Significant side-effects requiring change of treatment occurred in 10%. Disturbed behaviour was reported in 55% and 22% had a poor social outcome. 45% had complete control of fits clinically. This study showed that in Port Moresby acute meningitis is a significant cause of epilepsy in young children, the majority of whom present with grand mal epilepsy, which is usually controlled by phenobarbitone, a readily available and cheap drug and still a useful anticonvulsant in the developing world. PMID- 7863727 TI - Dumbbell schwannoma causing acute spinal cord compression: case report. AB - A case is presented of acute spinal cord compression by a thoracic dumbbell spinal schwannoma in a young woman with neurofibromatosis type 1 (NF-1). A successful outcome was achieved with total excision of the lesion and decompression of the spinal cord. Greater recognition of the reversibility of spinal cord compression in the developing world is necessary to reduce major permanent morbidity. PMID- 7863728 TI - Renal tubular acidosis in Papua New Guinea. AB - Unlike most other inborn errors of metabolism, which require advanced and expensive diagnostic techniques and complex drug and dietary management (often not feasible in developing countries), the renal tubular acidoses may be detected and treated both easily and cheaply. Diagnostic confusion is possible as this series demonstrates due to the protean clinical manifestations. Three recent cases from Port Moresby General Hospital are described and appropriate investigations and treatment discussed. PMID- 7863729 TI - The management of delayed presentation of acute appendicitis. PMID- 7863730 TI - Resistance of Plasmodium falciparum in vivo to 3 days' treatment with quinine and single-dose Fansidar. PMID- 7863731 TI - A comparative study of the effectiveness of mebendazole (Janssen) and generically equivalent mebendazole (Nordia) in intestinal helminthiasis in Papua New Guinean children. AB - Papua New Guinean schoolchildren in the highlands were randomly assigned to treatment groups in order to verify the effectiveness of mebendazole (Nordia) and compare it with mebendazole (Janssen) in both extended and single-dose therapy in a double-blind controlled study. Only the Janssen product given twice daily for three days was of value in 'curing' hookworm. Single-dose treatment with the same product was highly effective in treating roundworm but not hookworm or whipworm. Observations suggest that drug particle size may be an important determinant of efficacy against hookworm. Based on this study, the use of the Janssen formulation of mebendazole would be preferable. PMID- 7863732 TI - Blood serum transferrin concentration in cattle in various physiological states, in veal calves fed different amounts of iron, and in cattle affected by infectious and non-infectious diseases. AB - Transferrin (Tf) concentrations were determined in cattle in various physiological states, in energy-deficient (ketotic) cows, in situations of several acute and chronic infections, after endotoxin administration and in animals with bovine leucocyte adhesion deficiency (BLAD). Tf concentrations varied between 1.5 and 8.5 g/l and in healthy animals were in the range of 2.0 and 6.6 g/l. Tf concentrations in adult animals were smaller than in young animals and increased in veal calves with iron deficiency above 8 g/l, resulting in a negative correlation between Hb and Tf. In veal calves total iron binding capacity (TIBC) and Tf concentration were rather closely correlated (r = 0.63). Chronic infectious diseases (such as paratuberculosis) were characterized by relatively low Tf levels (below 2 g/l), while during acute infections, after endotoxin-administration and during ketosis Tf concentrations were not changed. PMID- 7863733 TI - Passage of a heterologous protein through ileal enterocytes of newborn piglets: immunolabelling of bovine serum albumin at the light- and electron microscopic level. AB - The passage of bovine serum albumin through ileum enterocytes of neonatal pigs was studied by light microscopy with indirect immunoperoxidase and by electron microscopy with post-embedding direct immunogold methods. Vacuoles filled with the heterologous protein were seen as early as 10 min after the administration of either bovine serum or solutions of bovine serum albumin by gavage. The sizes of vacuoles increased with time, their electron densities and immunoreactivities were at variance. The formation of albumin-containing vacuoles was independent of the concentration of the solutions fed, ranging from 1 to 7%. Bovine serum albumin becomes discernible in the capillaries at 4 h after feeding. By then, the intact albumin transported through enterocytes amounted to more than 10% of the circulating plasma proteins. Of several thousand enterocytes screened in the whole study only one--from the piglet 4 h after feeding--contained lysosomes. PMID- 7863734 TI - [Methodological aspects for the determination of the coagulative activity of coagulation factors II, V, VII and X from dog plasma]. AB - For optimization of single factor II, V, VII and X activity measurements in dogs, dilution series of dog pool plasma were prepared using different commercially available calcium thromboplastins and deficient plasmas. Measured by use of a canine reference curve, the single factor activity in humans was 89% (factor II), 13% (factor V), 27% (factor VII) and 84% (factor X). Because the factor V and VII activity in dogs is much higher than in humans, in measurements using human deficient plasma, a high sample predilution of at least 1:40 seems to be of advantage. Otherwise extreme variations of the factor V and VII activity may also influence the results of the other single factors. For determination of factor II, V and X activity, therefore, a non-standardized human placenta thromboplastin was especially suitable. With this reagent, the results were also reproducible at high sample dilutions (1:80, factor II and X; 1:160, factor V). Because of the low sensitivity of non-standardized human placenta thromboplastin to factor VII, measurements of this factor at a sample dilution of 1:40 required a standardized human placenta, or rabbit brain thromboplastin had to be used. For factor II measurements, the selection of a suitable deficient plasma is particularly important. Here, the reference curve showed a clear dependence on the commercial preparation chosen. PMID- 7863735 TI - Effects of growth hormone on growth performance, haematology, metabolites and hormones in iron-deficient veal calves. AB - Effects of subcutaneous (s.c.) administration of 50 micrograms/kg body weight of recombinant bovine growth hormone (rbGH) or saline were studied for 11 weeks in 40 intact male veal calves supplied 50 mg or 10 mg of iron (Fe)/kg of milk replacer (MR). Feed intake, average daily gain and growth: feed ratio were reduced in Fe-deficient calves, but not significantly influenced by rbGH. Plasma Fe and haemoglobin concentration, red-cell number and packed cell volume were decreased in Fe-deficient calves (P < 0.05) and rbGH further reduced red-cell number in Fe-deficient calves (P < 0.05). The age-dependent increase of total Fe binding capacity was greater in Fe-deficient calves and enhanced by rbGH (P < 0.05). Plasma urea concentrations increased, whereas glucose (G) and triiodothyronine (T3) levels decreased in Fe-deficient calves. rbGH significantly increased G in calves fed MR containing 50 mg/kg (P < 0.05) and influenced urea concentrations (P < 0.05). Plasma insulin (I) and IGF-I concentrations were lower in Fe-deficient calves (P < 0.05). Plasma GH in the first hours after rbGH injections increased (P < 0.05) to higher levels in calves fed 10 than in those fed 50 mg Fe/kg MR, but incremental changes were comparable. In conclusion, low Fe intake caused haematologic, metabolic and endocrine changes. Plasma IGF-I, I and T3 concentrations after rbGH administration and effects of rbGH on IGF-I in Fe-deficient calves were reduced, even though plasma GH levels were increased. PMID- 7863736 TI - Are muscarinic receptors involved in the effect of serotonin on gastrointestinal electrical activity in the conscious piglet? AB - In conscious piglets provided chronically with electrodes in the wall of the antrum pylori, duodenum, jejunum and ileum, the effect of intravenous infusion of 5-HT, 4 micrograms/kg/min for 2 h, with and without pre-treatment with atropine, 0.5 mg/kg, on gastrointestinal myoelectrical activity was studied. In the antrum, fast oscillations were partially inhibited by 5-HT and nearly completely blocked by the atropine/5-HT combination and by atropine alone. In the small intestine 5 HT induced a decrease in MMC interval, an increase in phase III activity in duodenum and jejunum and an acceleration of propagation velocity as measured for the jejunum. These effects were not influenced by atropine. Following atropine, phase II activity in the jejunum was significantly inhibited by 5-HT. The ileum was rather insensitive to 5-HT. It is concluded that the inhibitory effect of 5 HT on antral electrical activity is enhanced by atropine, and that 5-HT has a stimulatory effect on small intestinal activity which is not dependent on a muscarinic action. PMID- 7863737 TI - Enrichment of bovine X and Y spermatozoa by free-flow electrophoresis. AB - Conditions of separation of bovine spermatozoa according to their differences in electrophoretic mobility were studied using free-flow electrophoresis. Distribution of spermatozoa in the electric field depends on composition of buffer system, field intensities and temperature. Conditions are described for reproducible separation of anodically migrating spermatozoa into two distinct peaks both for cold-immobilized (10-13 degrees C) and for motile cells (25 degrees C). Electrophoresis with the buffer used at 25 degrees C and field intensities of 70-100 V/cm provided high percentages of motile spermatozoa (50 90%) in all fractions. However, the sperm distribution across the fractions was the result of superimposed passive electrophoretic motion towards the anode and the active galvanotactic migration towards the cathode. Separation of X- and Y spermatozoa was verified by quantification of Y-spermatozoa by means of both in situ hybridization, using Y-specific DNA fragments, and the Y-specific fluorescence staining (f-body test). Y-spermatozoa could be enriched in anodic fractions (112 and 144% relative to control). X-spermatozoa were enriched in cathodic fractions (80 and 68% Y-spermatozoa, as compared to control). PMID- 7863738 TI - Changes in osmotic fragility of nucleated erythrocytes resulting from blood storage. AB - The storage of blood for 24 h at 10 degrees C caused significant changes in osmotic fragility of nucleated erythrocytes of pigeons, peafowls, domestic fowls, lizards and toads. Significant decreases in fragility were seen with pigeon and peafowl erythrocytes. However, the osmotic fragility of domestic fowl, lizard and toad erythrocytes increased significantly. PMID- 7863739 TI - Serum fructosamine as a screening test for diabetes mellitus in non-healthy middle-aged to older dogs. AB - Diabetes mellitus is a common endocrine disorder among non-healthy middle-aged to older dogs. Previous studies have shown that serum fructosamine can be used to detect the chronic unregulated hyperglycaemia in Diabetes mellitus. The present study was therefore conducted to assess the value of serum fructosamine as a screening test for Diabetes mellitus among non-healthy middle-aged to older dogs in terms of sensitivity, specificity, positive and negative predictive values. A total of 99 non-healthy dogs (16 dogs with Diabetes mellitus and 83 dogs with other diseases) with an age ranging from 6 to 15 years were included in the study. Using the upper reference limit for serum fructosamine (343.8 mumol/l), sensitivity and specificity were 0.88 and 0.99, respectively and assuming the prevalence of Diabetes mellitus to be 0.05, the positive and negative predictive values were 0.82 and 0.99, respectively. Apparently, serum fructosamine could also be used to distinguish hyperglycaemia non-diabetic dogs from hyperglycaemic diabetic dogs. Thus, the present study showed that serum fructosamine is a reliable screening test for Diabetes mellitus among non-healthy middle-aged to older dogs. PMID- 7863740 TI - Metastatic adenocarcinoma of a minor salivary gland in a cat. AB - Neoplasms derived from salivary glands are uncommon in domestic animals and descriptions of neoplasms derived from minor salivary glands are quite rare. A primary neoplasm derived from a minor salivary gland is described in a 13-year old domestic shorthair cat. The oral neoplasm was locally invasive, and had metastasized to the regional lymph nodes and hilus of the lungs. PMID- 7863741 TI - [The activity of transport ATPases and the characteristics of the protein-lipid composition of the membranes of anuclear erythrocytes in a number of mammals]. AB - The activity of Na,K-ATPase and Ca-ATPase of the intact erythrocytes and their membrane preparations and also fatty acid, phospholipid and protein content of erythrocyte membrane of guinea pig, mouse, rabbit and hamster have been examined. The activity of Na,K- and Ca-ATPase in intact erythrocytes varies significantly among different species while the level of activity of these enzymes in their membrane preparations differs slightly. Together with the results of investigations of chemical composition of the erythrocyte membrane of these species which show the principal homogeneity of their fatty acid, phospholipid and protein composition, these data indicate the existence of the system of intracellular modulators, that maintain the activity of these enzymes on the species specific level. PMID- 7863742 TI - [A comparative study of the physicochemical and antigenic properties of human and animal albumins]. AB - Studies have been made on physico-chemical and antigenic properties of albumins from man, mammals, birds, insects, amphibians, worms, fishes and crustaceans. It was found that all the animals contain structurally identical proteins with similar physico-chemical properties. At the same time, the level of antigenic identity of the proteins decreases in the following order: type, genus, family, species. PMID- 7863743 TI - [The growth-stimulating activity of the insulins from teleosts]. AB - Growth-stimulating properties of insulins from cyclostomes, teleosts and mammals were evaluated by their capacity to promote the uptake of [35S]-sulfate by fish branchial cartilages. It was shown that all the tested hormones exhibit promotor properties increasing the uptake of labeled sulfate by 1.5-3 times. The effects depend both on the dose of the hormone and on peculiarities of its molecular structure. PMID- 7863744 TI - [The characteristics of the binding of M-cholinergic blockers and beta adrenoblockers by the brain synaptosomes of 15-day-old and adult rats]. AB - Significant difference in values of basic parameters, Bmax and Kd which characterize binding of 3H-quinuclidynylbenzylate and 3H-dihydroalprenolol, specific blockers of m-cholino- and beta-adrenoreceptors, has been established for brain synaptosomes from 15-day and adult rats. It was shown that phospholipase A2 (1 microgram/ml), a membrane active component from the venom of the cobra Naja naja oxiana, reduced Bmax and Kd for binding 3H quinuclidynylbenzylate and 3H-dihydroalprenolol by synaptosomes. It is suggested that functional modifications in membrane during animal development or induced by phospholipase A2 result in shifts in the specific activity of adreno- and cholinoreceptors and, as a result, in disturbances of adrenergic and cholinergic responses. PMID- 7863745 TI - [The effect of the isolated or group housing of rat pups weaned at different times from the lactating female on the development of a spectrum of digestive enzymes in the small intestine]. AB - Studies have been made on the formation of the spectrum of digestive enzymes in the small intestine of weanling rats which were taken from lactating female and given semisynthetic food at the age of 17, 21 and 25 days. It was shown that the rate of general development and maturation of the digestive enzymes depends on the age of animals and the mode of their breeding (isolated or in a group of the same age). These factors significantly affect also the level of the activity and proximo-distal gradient of distribution of the following intestinal enzymes: lactase, sucrase, alkaline phosphatase, alanine aminopeptidase, glycyl-L-leucine dipeptidase, as well as the mass of the mucose and protein content of the small intestine. PMID- 7863746 TI - [Differences in the reaction of old and young rats to immobilization stress]. AB - Studies have been made on the reaction of 55 male old and young Wistar rats to acute 1-hour immobilization. Corticosterone was determined in the blood serum using radioimmune assay. Similar phasic changes in the level of corticosterone in the blood serum were revealed in young and old rats, although in the latter these changes occurred 1 day later. The decrease in the body weight and in the mass of the adrenals was also observed which was more significant in old animals. PMID- 7863747 TI - [The hidden symmetry and evolution of the primary structure of myoglobin]. PMID- 7863749 TI - [Professional staff training]. PMID- 7863748 TI - [The theory of A. M. Ugolev on the excretory origin of secretory processes]. PMID- 7863750 TI - [Measures related to epidemiology, prevention, and control of leprosy]. PMID- 7863751 TI - [Consumer and community participation in care and readaptation programs targeted to people with leprosy]. PMID- 7863752 TI - [Management of physical disabilities]. PMID- 7863753 TI - [Guidelines for the administrators of campaigns against leprosy]. PMID- 7863754 TI - [Determining factors of non-compliance among patients undergoing polychemotherapy in the district of Bamako (Mali)]. AB - In order to examine the factors determining irregularity among patients undergoing multidrug therapy in Bamako district, we conducted a non-experimental study based, in the first instance, on medical records and later on a questionnaire. One thousand one hundred and seventy-five (1,175) treatment cards were reviewed in this way. The results of our study show that 3.1% of the patients fail to attend treatment sessions regularly and that multibacillary patients have more irregular attendance than paucibacillary patients. We have not observed any statistically meaningful difference between old and new patients as far as irregularity in attending multidrug therapy sessions is concerned. The second part of our research based on a questionnaire targeting a group of cases (36 patients who did not attend regularly) and a random control group (50 patients who attended treatment regularly but had missed at least one treatment) has shown that it is only for Item VI ("Have you ever missed your appointment because you perhaps considered yourself cured?") that a statistically meaningful difference emerges between cases and controls regarding the rates of affirmative responses (p < 0.05). PMID- 7863755 TI - Surgical correction of saddle nose deformity in leprosy--one stage procedure. AB - In twenty-four leprosy patients having mild to moderate nasal deformity, a corticoperiosteal bone graft obtained from second metatarsal bone was placed in a pocket created between the lining and cover of the nose. The cases were evaluated later, mean follow-up period being 4 1/2 years. The results were satisfactory in 13 patients. Improved shape was reported in 7 and poor in 3. The bone graft got incorporated and consolidated at the recipient site in 16 cases. The main donor site problem was overriding of the donor toe. The operated cases need health education for after-care of nose since nasal mucosa is atrophic. PMID- 7863756 TI - Agreement between histopathological results in clinically diagnosed cases of indeterminate leprosy in Sao Paulo, Brazil. AB - Histopathological slides from skin biopsies of fifty-seven self-reporting patients diagnosed as indeterminate leprosy by the Leprosy Control Programme in Sao Paulo, were sent to three independent histopathologists. Agreement between the reports were based on the following diagnosis: "indeterminate leprosy", "suggestive leprosy" or "no leprosy". A great variation was observed in the interpretation of the histopathological examination. The three pathologists reported "indeterminate leprosy" respectively in 7.0%, 54.4% and 84.2%, of the cases studied. A kappa index of agreement between any two pathologists ranged from 0.08 to 0.32, showing poor agreement between observers. Agreement improved by pooling together the reports "suggestive leprosy" and "indeterminate leprosy". The three pathologists agreed in the results of 24 biopsies of the 27 classified as leprosy by any one of the three observers. Eight cases were considered as "no leprosy" by all pathologists. Higher agreement indices were obtained for positive and negative proportionate concordance between any two examiners. The implications of the variation in the diagnosis of indeterminate leprosy and early leprosy are discussed in the context of public health and case-management. PMID- 7863758 TI - Tissue reactions to cemented hip sockets. Histologic and morphometric autopsy study of 25 acetabula. AB - To gain an insight into the tissue reactions leading to noninfectious loosening, 25 autopsy specimens of acetabula with well-fixed cemented sockets were analyzed histomorphologically and morphometrically. The mean duration of the implant was 7 (0.2-16) years. With the exception of some focal direct bone-cement contacts, bone and cement were separated by a soft tissue membrane which increased in thickness with increasing duration of the implant. Necroses in the membrane were also commoner with advancing implant time. The soft tissue membranes developed increasingly dense infiltrates of histiocytes, mainly containing wear particles of the bone cement and--though less abundant--polyethylene. The cancellous bone adjacent to the soft tissue membrane showed an increasing histiocytic infiltration with an increasing duration of the implant. The trabecular bone showed remodeling with formation of a neocortical layer parallel to the border of the cement mantle. PMID- 7863757 TI - Immunoprecipitation of mycobacterial antigens with sera from patients with leprosy. AB - Pooled sera from leprosy patients across the clinical spectrum, tuberculosis patients and healthy individuals were tested for their reactivity with antigens of Mycobacterium leprae and a panel of cultivable mycobacteria by immunoprecipitation technique. Sera from lepromatous leprosy patients demonstrated exclusive reactivity with the 26-kDa protein of M. tuberculosis H37Ra, 28-kDa protein of M. kansasii, 45-kDa protein of M. smegmatis, and 158, 40 and 14 kDa proteins of M. phlei. Sera from patients with borderline tuberculoid leprosy, tuberculoid leprosy, tuberculosis and health individuals failed to identify these antigens. Our studies indicate that analysis and characterization of immunodominant antigenic epitopes present on proteins of cultivable mycobacteria, sharing cross-reactive epitopes with M. leprae may prove to be important in the serodiagnosis of multibacillary leprosy as well as for developing vaccines for immunotherapy of leprosy. PMID- 7863759 TI - Early failure with Boneloc bone cement. 4/8 femoral stems loose within 3 years. AB - 1 performed 8 hybrid total hip replacement using Boneloc bone cement. After 32 (28-36) months, 2 reoperations were performed for femoral component loosening and in another 2 cases, the femoral components were loose, as shown on radiographs. The cement was fragmented in the proximal femur and easily removed. PMID- 7863760 TI - Intravenous cefuroxime prophylaxis. Tissue levels after one 3-gram dose in 40 cases of hip fracture. AB - This study consists of 2 series of patients with cervical hip fracture treated with hemiarthroplasty. In a preliminary study, the method, timing of sample collection, and tissue and serum concentrations were studied in 15 patients. In the main study of another 25 patients, only tissue samples were collected. In the preliminary study, 3 g of cefuroxime was infused in 15-25 min and serum, muscle, fascia and bone samples were collected at various times. In the main study, 1 dose of 3 g of cefuroxime was infused in 15 min. Skin, muscle, fascia, and bone tissue samples were collected after 30 and 45 min and the concentrations of cefuroxime were measured by high-performance liquid chromatography. In the preliminary study, serum cefuroxime levels were 61 micrograms/mL and 42 micrograms/mL at 15-30 and 35-50 min, respectively. Cefuroxime levels in various tissues were only slightly less than those in serum. Blood contamination contributed less than 30 percent to the tissue levels of cefuroxime. In the main study, mean cefuroxime levels in the tissues were in the range of 39-58 micrograms/g, and the total range was 5.5-151 micrograms/g at 30 and 45 min. These concentrations are well above the MIC values of the most common bacteria causing wound and bone infections. PMID- 7863761 TI - Air contamination during hip and knee arthroplasties. Horizontal laminar flow randomized vs. conventional ventilation. AB - In a randomized study 90 patients, operated on with a total hip or knee arthroplasty, were allocated to 1 of 3 different regimes, all including a reinforced single-use operating gown: (1) horizontal laminar flow ventilation and conventional clothes (cotton shirts and trousers) for all staff members, (2) horizontal laminar flow ventilation and occlusive garments (Klinidress) and (3) conventional ventilation and occlusive garments. Volumetric air sampling gave a low mean number of colony-forming units (< 10 cfu/m3) in the vicinity of the wound in all 3 groups. Laminar ventilation, with or without occlusive staff garments, resulted in less air contamination compared to conventional ventilation. During knee arthroplasty, the use of occlusive clothes in the laminar ventilation room, further reduced the number of airborne, bacteria carrying particles to around 1 cfu/m3. No such reduction was seen during hip arthroplasty. We conclude that hip and knee arthroplasties can be performed in operating theaters with conventional ventilation when occlusive staff garments are used. However, laminar air flow ventilation in knee surgery, preferably in combination with occlusive garments, resulted in a substantially lower air contamination and should be preferred. PMID- 7863762 TI - The stability of three different cementless tibial components. A randomized radiostereometric study in 45 knee arthroplasty patients. AB - We conducted a prospective, randomized study of 45 patients to evaluate 3 different uncemented tibial component designs in total knee arthroplasty. The stability of the components was assessed by radiostereometry (RSA), both as migration during 2 years and as inducible displacement at 2 years. The PCA resurfacing, the Tricon stem and the Tricon-M prosthesis groups showed a similar level of migration at 2 years, about 1.4 mm. In response to externally applied rotatory forces, the Tricon groups rotated more than the PCA group, interpreted as a consequence of the more conforming articular surface in the Tricon design. The series was divided into one group of continuously migrating prostheses with a poor prognosis (unstable, one third) and another group of prostheses in which migration stopped after 1 year (stable, two thirds). With this classification, no differences between the prostheses design groups were revealed. However, the unstable group showed a larger inducible displacement by provocation, an association hitherto not established. PMID- 7863763 TI - High intrinsic healing potential of human anterior cruciate ligament. Organ culture experiments. AB - We studied the intrinsic healing capacity of human semitendinosus tendon specimens, comparing them to human anterior cruciate ligament specimens collected at the time of ligament reconstructions, and using an organ culture model. On the day after cultivation, migration of cells and synthesis of collagen fibers were observed in the ligament group with preserved synovium (PS), the ligament group with resected synovium (RS), and the semitendinosus tendon group (ST). Migrating cells and newly-formed collagen fibers were most prominent in the PS group, followed by the RS, and ST groups. When the area occupied by the migrating cells and newly-formed collagen fibers in the prepared hole was measured, no differences were observed between the groups at week 2. However, differences were noted between the ST and PS or RS groups at weeks 4 and 6. Our findings indicate that the human anterior cruciate ligament possesses a high intrinsic healing capacity. It is also suggested that the synovium plays an important role in enhancing ligament healing capacity. PMID- 7863764 TI - Leg lengthening and glycosaminoglycans in the rabbit knee. AB - We investigated the effects of tibial lengthening by callotasis on glycosaminoglycan (GAG) metabolism of the knee articular cartilage in 30 rabbits. The distraction rate was 1 mm per day. On the right side, the daily distraction was in 2 steps, while on the left it was in 120 steps. The animals were divided into 3 subgroups based on length gain; 10, 20, and 30 percent, respectively. The knee joint fluid and medial tibial cartilage were examined by quantitative analysis of the GAG content and/or synthesis. The immunoreactivity for chondroitin sulfate in the cartilage was also examined by immunohistochemistry. For all length gains, the GAG concentration in the synovial fluid was higher on both sides than in controls, with no difference between sides. The GAG content and synthesis in the cartilage on the 2-step side decreased gradually with increasing length. On the 120-step side, the content did not differ from control values in any length gain, and the level of synthesis at 20 and 30 percent lengthening was higher than the control level. Our findings indicate that the alterations in GAG metabolism are attributable to increased mechanical stress on the articular cartilage, suggesting a moderate increase on the 120-step side compared to an excessive one on the 2-step side. PMID- 7863765 TI - Meniscal repair by synovial flap transfer. Healing of the avascular zone in rabbits. AB - We studied repair of a longitudinal incision of the right medial meniscus in 44 rabbits after the transfer of a pedunculated synovial flap, without immobilization of the knee. The left medial meniscus was used as the control, after creating the same lesion without synovial flap. Healing was analyzed by histologic studies, including India ink perfusion after 8, 12, 24, and 48 weeks. In three quarters of the cases, the meniscus showed healing with vascularization of an originally avascular zone. PMID- 7863766 TI - 3 cases of longitudinal stress fracture of the tibia. PMID- 7863767 TI - Treatment of brachymetatarsia using a semicircular lengthener. 1-3 years results in 6 patients. AB - 6 women with brachymetatarsia involving 9 bones were treated by the use of the Ilizarov semicircular lengthener. The affected bones were the second, third and fourth metatarsals. Ilizarov half-rings were applied on the foot with 5 or 6 half pins (3 mm in diameter) and a percutaneous osteotomy was done. The short metatarsals were lengthened 0.25 mm twice a day by the patient. The lengthened distance was 15 (10-22) mm and the overall treatment time was 15 (12-25) weeks. The postoperative course was uneventful, with smooth bone regeneration. No bone grafting was needed. During treatment, the patients could bear full weight and tolerated the fixators well. We conclude that this technique is useful in the treatment of brachymetatarsia. PMID- 7863768 TI - Ultrasound attenuation of the calcaneus in normal subjects and in patients with wrist fracture. AB - We determined broadband ultrasound attenuation (BUA) of the calcaneus, and bone mineral density (BMD) of the spine, proximal femur and radius in 137 healthy subjects (79 women and 58 men) and in 56 women with Colles' fracture. The repeated measurements on 9 healthy subjects indicated a short-term reproducibility (coefficient of variation) of 4 percent for BUA. There was a small (7 percent) but significant difference in BUA between normal men and women. The age-dependence in normal subjects was weak. When all the study subjects were pooled, modest correlations between BUA of the calcaneus and BMD at all measured skeletal sites were found (rs values 0.3-0.4). However, it was not possible to make an accurate prediction of the axial BMD, using BUA. BUA values were 13 percent lower in the wrist fracture patients than in the age-matched normals. In general, BUA could discriminate the fracture patients from normals as effectively as BMD. As suggested by the physical theory of ultrasound attenuation, our results support the idea that BUA reflects not only the bone density but also other factors related to the structural properties of bone. PMID- 7863769 TI - Effect of the shoe on plantar foot pressures. AB - The bare foot plantar pressures were compared to in-shoe pressure measurements in 11 normal male volunteers using the EMED system. Shoes diminished pressures and forces in most areas under the foot except the medial forefoot. The hallux showed less force, a smaller contact area and a reduced contact time. Therefore a shoe can interfere with the toe-off mechanism. There was no difference between various types of shoes with rubber and leather soles. Heavier subjects tended to put less weight on the medial forefoot. PMID- 7863770 TI - Tuberculosis of the elbow. A report of 10 cases. AB - We treated 10 cases of tuberculosis of the elbow with a 9-month antitubercular drug regimen, and surgery when indicated. The diagnosis was confirmed in 8 cases by histopathological examination and 2 cases were treated on clinical radiographic grounds. The follow-up ranged from 1 year to 3 years. The results were excellent in synovial and extraarticular lesions. Only in cases with minimal involvement of articular cartilage was a good range of movement achieved. PMID- 7863771 TI - Wound healing after total elbow replacement in rheumatoid arthritis. Wound complications in 50 cases and laser-Doppler imaging of skin microcirculation. AB - Wound healing complications, predisposing to deep infection, are common following prosthetic surgery of the elbow. 50 capitellocondylar elbow prostheses were inserted, using a lateral approach, in 42 patients with rheumatoid arthritis. The first 5 elbows were immobilized postoperatively for 5 days and the following 45 elbows for 12 days, because of delayed wound healing in 2 of the first 5 elbows. No wound healing complications were recorded in elbows immobilized for 12 days and elbow motion was not compromised. 5 elbows were investigated with laser Doppler imaging (LDI) technique, both pre- and postoperatively. Postoperative LDI values were considerably higher than preoperative ones, indicating no impairment of local skin microcirculation. The authors conclude that the lateral approach is safe to use in prosthetic surgery on the elbow. Early mobilization can delay wound healing, but this can be prevented by 2 weeks of postoperative immobilization. PMID- 7863772 TI - Pigmented villonodular synovitis. Monoclonality and metastasis--a case for neoplastic origin? AB - We report a 48-year follow-up of a case of recurrent pigmented villonodular synovitis of the knee. Subcutaneous metastasis to the contralateral thigh was an unusual finding. Histology demonstrated fibroblastic and histiocytic proliferation, as well as increased mitotic activity in recurrent lesions. Cytogenetic analyses demonstrated monoclonality and chromosomal abnormalities. Our findings support a neoplastic origin of this lesion. PMID- 7863773 TI - Collagen with gentamicin for prophylaxis of postoperative infection. Staphylococcus aureus osteomyelitis studied in rabbits. AB - In 34 rabbits, both tibiae were inoculated with Staphylococcus aureus. 14 legs received no treatment and served as controls. In 12 legs, the wound was treated with pure collagen and in 18 legs, collagen with gentamicin (Gentacoll) in a dose of 10 mg/kg body weight was applied to the wound before closure. Postoperatively 12 received 10 mg/kg body weight gentamicin intravenously and no local treatment. The animals were killed 7 days after inoculation and evaluated macroscopically and microbiologically for infection. 6 rabbits (12 legs) were used for pharmacokinetic studies only and they were killed after 2, 4, and 18 hours, respectively. 11/14 untreated legs developed a macroscopically acute osteomyelitis. No infection was found in the 18 legs treated with Gentacoll and 1/12 treated with gentamicin systemically had growth of the inoculated bacteria in tissue biopsies. The concentrations of gentamicin in the serum as well as locally reached peak values were well above the MIC value in all groups, with a maximum after 1-2 hours. No gentamicin could be detected after 18 hours, independently of the mode of administration. PMID- 7863774 TI - Proteoglycan degradation in hemarthrosis. Intraarticular, autologous blood injection in rat knees. AB - We determined the degradation of articular cartilage proteoglycans in a single episode of experimental hemarthrosis in rat knees. The right knee joints of rats were injected once with autologous whole blood. Both knee joints were examined histologically. Biochemical studies of cartilage proteoglycans extracted from the knees were also conducted. Histological examination revealed an accumulation of mononuclear cells in intraarticular fibrin clots and subsynovial layers 8 hours after the injection of blood. Accordingly, initiation of proteoglycan degradation occurred 8 hours after injection of blood, lasting from 1 day of limited degradation to 3 days; recovery then occurred within 7 days. The proteoglycan degradation could be inhibited by 1 mM phenylmethylsulfonyl fluoride, a general serine proteinase inhibitor, 0.1 M 6-aminohexanoic acid, a specific inhibitor of plasminogen activators, 10 mM EDTA, and 10(-6) to 10(-8) M dexamethasone, indicating that the accumulation of mononuclear cells in intraarticular fibrin clots and subsynovial layers may play an important role in cartilage damage. PMID- 7863775 TI - Three-dimensional MRI reconstructions of musculoskeletal tumors. A preliminary evaluation of 2 cases. AB - We have developed a new method for three-dimensional (3D) reconstruction of malignant bone and soft-tissue tumors from MRI. Data from transverse images of T2 weighted images were transferred into a personal computer. The contours of tumors, major vessels, major nerves and bones were outlined, whereupon the 3D data were processed into a 3D display, using a solid model. The determination of tumor volume both before and after preoperative adjuvant therapy was quantified. The 3D images allowed a better understanding of the relationship between the tumor and the major vessels and nerves, thereby aiding in preoperative planning. The images also provided a quantitative, reproducible measurement of the effect of adjuvant therapy. PMID- 7863776 TI - An orthopedic complication-registration system. PMID- 7863777 TI - Microvascular obstruction in avascular necrosis. Immunohistochemistry of 14 femoral heads. AB - 14 femoral heads with late stage avascular necrosis of different etiologies were histologically examined, with special attention to vascular structures. Decalcified slices were stained with hematoxylin-eosin, safranin-O, van Gieson stain, and Martius Scarlet Blue. Immunohistochemical techniques with antibodies against Factor VIII, and Ulex Europeus Lectin were used to visualize the endothelium of the blood vessels. 5 distinct zones of the necrotic femoral head could be identified. The necrotic zone contained areas with richly vascularized connective tissue. In the transitional zone, several areas with intravascular aggregations of newly formed and older fibrin clots were noticed, mainly on the venous side of the vascular system. Other small vessels were collapsed, with a few endothelial cells clumped together in the center of a concentric fibrous tissue. We suggest that obstruction to the venous outflow due to intravascular thrombosis as well as to perivascular fibrosis is important in the pathogenesis of non-traumatic avascular necrosis of the femoral head. PMID- 7863778 TI - Prevention of fractures in the elderly. A review. PMID- 7863779 TI - Delayed rupture of the thumb extensor tendon. PMID- 7863780 TI - [Protective effects of ginsenosides on oxygen free radical induced damages of cultured vascular endothelial cells in vitro]. AB - In this study, calf aortic endothelial cells (ECs) were cultured in vitro to study the ECs damages induced by exogenous oxygen free radical (OFR), and the protective effects of ginsenosides. Exogenous OFR was generated by three methods: enzyme reaction (xanthine-xanthine oxidase), chemical reaction (Cu(2+)-ascorbate) and electrolysis. The experimental results indicated that the xanthine-xanthine oxidase method is most suitable for the study of free radical mediated ECs damages. Addition of ginsenosides (40 microliters.ml-1) reduced the concentration of MDA in the cultured ECs, while the 6-keto-PGF1 alpha content in the medium was reduced (P > 0.05) and the morphologic damages of the ECs was alleviated. It is concluded that ginsenosides exerted a protective effects on ECs damages against lipid peroxidation, and ginsenosides might play an important role in antiatherosclerosis through its protective effect on endothelial cells. PMID- 7863781 TI - [Effects of m-nifedipine on activities of Na+,K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase in myocardium and brain of elderly renovascular hypertensive rats]. AB - Clipping the left renal artery induced marked hypertension and hypertrophy of the left ventricle in elderly (24-month-old) rats. m-Nifedipine (m-Nif, ig 20 mg.kg 1, qd x 9 wk) significantly decreased the systolic blood pressure and the weight of the left ventricle in the renovascular hypertensive rats (RVHR). In RVHR, the activities of Na+, K(+)-ATPase and Ca(2+)-ATPase in microsomes of the myocardium and brain were reduced significantly compared with those in sham-operated rats. m Nif was found to increase the activities of these enzymes of the myocardium and brain in elderly RVHR (P > 0.01). m-Nif 10-1000 mumol.L-1 in vitro elevated the activities of Na+, K(+)-ATPase and Ca(2+)-ATPase in the myocardium and brain of RHVR. On the contrary, the myocardial and cerebral Mg(2+)-ATPase activities were higher in RVHR than in sham-operated rats. m-Nif was shown to depress markedly this enzyme both in vivo and in vitro. These results indicate that m-Nif can improve the activities on Na+, K(+)-ATPase and Ca(2+)-ATPase in the myocardium and brain in elderly RVHR. PMID- 7863782 TI - [Oxytocin provoke intracellular calcium ion concentration in dispersed decidua cells of late pregnant rats]. AB - It has been postulated that hormonal signal acts upon decidua and ammion to trigger labor via production of PGs. In our experiment the decidua cells of pregnant rats (day 19) were digested and dispersed to test the effect of oxytocin on intracellular calcium ion concentration [Ca2+]i which was measured with the fluorescent dye fura-2. Addition of oxytocin 0.001-1 mumol.L-1 to the test system resulted in a dose-dependent transient increase in [Ca2+]i which peaked within 15 s and returned to base line in 12 min. Repeated addition of oxytocin 1 mumol.L-1 failed to elicit a repeated response. In the decidua cells of dihydroepiandroterone sulfate-treated pregnant rats, the [Ca2+]i peak provoked by oxytocin was significantly higher than in the controls. These results suggest that oxytocin may activate the inositol-phospholipid-protein kinase C effector system in decidua cells of pregnant rats. Dihydroepiandrosterone sulfate may influence the action. PMID- 7863783 TI - [Inhibition of protein kinase C by stilbenoids]. AB - The effect of 15 stilbenoids on protein kinase C (PKC) was studied in order to search for naturally occurring PKC inhibitors. All these compounds were isolated from Chinese medicines. Three oligomeric stilbenes from Caragana sinica, alpha viniferin, kobophenol A and miyabenol C, were shown to intensely inhibit the activity of partially purified rat brain PKC with IC50 values of 62.5, 52.0, and 27.5 mumol.L-1, respectively. Kinetic analyses revealed that that inhibition was noncompetitive. The other compounds also showed the effect. Monomer stilbenes exhibited PKC inhibitory activity at higher mumol.L-1 concentrations than oligomeric stilbenes. Whenever they are methylated or acetylated perfectly, the inhibition weakens or disappears. PMID- 7863784 TI - Determination of 2-bromo and 2-chloro derivatives of 2'-deoxyadenosine in human blood serum by high performance liquid chromatography. AB - The aim of this study was to determine 2-chloro, and 2-bromo derivatives of 2' deoxyadenosine (2-CdA and 2-BdA respectively) in the serum of human blood by high performance liquid chromatography (HPLC). 2-CdA is a substance with anticancer and immunosuppressive activity. Caffeine or 5,6-dimethylbenzo-1,2,4-triazole-1 beta-D-ribofuranoside was added to 1 cm3 of serum as internal standard. 2-CdA and 2-BdA were isolated from serum using acetone as deproteinizing reagent. LiChrosorb Si 60 column was used for the separation of drugs and the internal standard from endogenous compounds in the sample. A mixture of potassium dihydrophosphate-methanol was used as a mobile phase. PMID- 7863785 TI - The availability "in vitro" of magnesium formulations using various leaching media. AB - The aim of this study was to determine the availability "in vitro" of magnesium ions from five tablet formulations. In our experiment the flow-through method according to Grzesiczak was used. The leaching media in above method were: an aqueous solution of hydrochloric acid at pH 1.0 used as artificial stomach fluid, an aqueous solution of hydrochloric acid at pH 4.0 and physiological salt solution. PMID- 7863786 TI - Preparation and activity of derivatives of 1,2,3,4-tetrahydroisoquinoline- 4,6,8 triol, as potential beta-adrenergic blockers. AB - The new derivatives of 1,2,3,4-tetrahydroisoquinoline-4,6,8-triol were synthesized as a potential beta-adrenergic blockers. These compounds were obtained by simple modification of beta-adrenergic agonists (terbutaline, orciprenaline, fenoterole) and evaluated pharmacologically for their activity and binding to beta-adrenoreceptor. PMID- 7863787 TI - Synthesis and pharmacological properties of some new 3-(2-N,N-dialkylaminoethyl) pyrido [2,3-d]-pyrymidin-4-ones. AB - The following new derivatives of pyrido [2,3-d]-pyrimidin-4(3H)-one were synthesized: 3-(2-N,N-dimethylaminoethyl), 3-(2-N-pyrolidynylethyl), 3-(2 piperidinylethyl) and 3-(2-N-morpholidinylethyl). Their chemical structures were confirmed by MS, IR and 1H NMR spectroscopic data. Newly synthesized compounds were investigated pharmacologically for their central properties in mice and rats. It was shown that compound [III] showed anxiolytic action in the four-plate test and two compounds produced analgesic effects in mice. PMID- 7863788 TI - Effect of mestranol on pharmacokinetics of paracetamol. AB - The aim of this study was to investigate the effect of mestranol on pharmacokinetics of paracetamol. The study was carried out on 20 female rabbits. Paracetamol was administered to rabbits intragastrically at a dose of 50 mg/kg b.w. One group of animals was given mestranol intragastrically 0.1 mg once daily during 2 months. The method of Routh A. et al. was used to paracetamol concentration assay. Blood for the assays was collected within 24 hours after drug administration, prior to the study as well as 1 month and 2 months after continuous mestranol administration. The two compartment open model was used for calculations. The study revealed an increase in AUC and paracetamol half-life as well as decrease in the total body clearance. We conclude that there is an interaction between mestranol and paracetamol leading to a decrease in total body paracetamol clearance. PMID- 7863789 TI - Central action of glaucine in rodents. AB - It was found that glaucine (7, 14 and 28 mg/kg ip) decreased locomotor activity, did not affect the body temperature and potentiated the amphetamine and apomorphine stereotypy but did not affect the amphetamine hypermotility. Besides, glaucine antagonized haloperidol-induced catalepsy of the rats. Glaucine was without analgesic, anticonvulsant, antianxiety and antidepressive effects in mice. This alkaloid in doses of 14 and 28mg/kg ip antagonized the head twitch response induced by 5-HTP in the rats. Further, glaucine decreased the hyperthermia induced by m-CPP in rats kept at high ambient temperature. It was found that glaucine depressed the noradrenaline (NA) and dopamine (DA) levels in the whole brain of mice. Besides, this alkaloid significantly decreased the brain level of 5-hydroxytryptamine (5-HT), without changing the 5-hydroxyindoleacetic acid (5-HIAA) concentration. PMID- 7863790 TI - Antihypertensive treatment with beta blockers and gabaergic transmission in rat brain. AB - The effects of chronic oral administration of propanolol and metoprolol on blood pressure and GABAergic function were investigated in spontaneously hypertensive rats (SHR) and compared with the effect of dihydralazine. Under the experiment conditions employed all drugs reduced significantly (p < 0.01) arterial pressure. The beta blockers elevated GABA turnover in the hypothalamus and the pons medulla. Dihydralazine, however had not such an effect. Our result suggest that the antihypertensive action of beta blockers may be related in part to the enhanced cerebral GABAergic transmission. PMID- 7863791 TI - The influence of molar mass of oligosaccharides on their ability to disperse iron hydroxide (III). AB - The ability of oligosaccharides to disperse iron hydroxide (III) was investigated. It was found that products of electrochemical oxidation of oligosaccharides (aldonic acid) exhibit higher dispergation activity them the corresponding oligosaccharides. PMID- 7863792 TI - Physico-chemical interaction between sodium alginate (ALG-Na), polyvinylpyrrolidone (PVP), sodium carboxymethylcellulose (CMC-Na) and solvent. AB - Physico-chemical interactions between sodium alginate (ALG-Na), polyvinylpyrrolidone (PVP), sodium carboxymethylcellulose (CMC-Na) and solvent were examined. The performed studies involve effect of concentration of macromolecule compounds, electrolytes and pH value of the system. Non-Newtonian system were described by pseudoplasic coefficient and thixotropic coefficient - B and M. These coefficients allow to estimate quantitatively rebuilding of macromolecular structure. PMID- 7863793 TI - The effects of zinc oxide and diethyldithiocarbamate on the mitotic index of epidermal basal cells of mouse skin. AB - The purpose of this study was to investigate the effects of topical treatment with zinc oxide (2.5%, 10%, 25% and 50%) and intraperitoneal treatment with diethyldithiocarbamate (DEDTC) (50 mg/kg, 500 mg/kg and 1,000 mg/kg) on the mitotic index of epidermal basal cells in incised and non-incised mouse skin. The present results showed that topical application of zinc oxide (25% and 50%) increased the mitotic index of epidermal basal cells in incised skin and non incised skin. Conversely, intraperitoneal administration of DEDTC (500 mg/kg and 1,000 mg/kg) decreased the mitotic index, but only in the incised skin. These results suggest that mitosis of epidermal basal cells may be stimulated by the topical application of zinc oxide both in incised and non-incised mouse skin, and that it also may be inhibited by the intraperitoneal administration of DEDTC in incised mouse skin. PMID- 7863794 TI - Suppression of hepatic natural killer activity by liver metastasis of cancer and restoration of killer activity by oral administration of a Basidomycetes-derived polysaccharide, PSK. AB - PSK (Krestin) is a protein-bound polysaccharide with antitumor and immunomodulatory activity. In this study, the effects of the oral administration of PSK were investigated on the natural killer (NK) activity of liver-associated lymphocytes and their subfractions separated by density gradient centrifugation, in WKAH rats with liver metastasis of KDA hepatoma. PSK was administered orally, at a dose of 500 mg/kg once a day for 3 weeks. The NK activity of nonparenchymal liver cells (NPLC) and their subfractions, including large granular lymphocytes (LGL), was markedly augmented by this treatment. The effects of oral PSK were also examined in CDF1 mice with liver metastases of Colon 26 adenocarcinoma; the survival of tumor-bearing mice was prolonged and both metastatic foci and liver weight were decreased. These results suggest that PSK may be effective for the suppression of liver metastasis through activation of liver-associated NK cells. PMID- 7863795 TI - Immunohistochemical analysis of epithelial cell proliferation in normal-appearing rectal mucosa of patients with colorectal adenoma and cancer using an in vitro labeling method with bromodeoxyuridine. AB - To identify diffuse mucosal changes which may precede the development of colorectal cancer and a possible indicator for detecting high-risk populations, we immunohistochemically studied cell-cycle events in crypts of normal-appearing rectal mucosa of patients with colorectal adenoma and cancer using an in vitro labeling method with bromodeoxyuridine (BrdU). Biopsy specimens of endoscopically normal-appearing rectal mucosa were obtained during colonoscopy from 20 patients with colorectal adenocarcinoma, 20 with adenoma, and 15 without apparent colorectal diseases. The specimens were incubated with BrdU in vitro, and labeled S-phase cells were identified immunohistochemically using a monoclonal antibody to BrdU. Modification of the BrdU-labeling pattern in the normal appearing rectal mucosa, such as the presence of BrdU-labeled cells at the mucosal surface or in the upper one-fifth of the crypt column, was observed in 15 of the 20 patients with adenocarcinoma, 17 of the 20 patients with adenoma and 6 of the 15 controls. This upward shift in the frequency of proliferating cells in the crypt was significantly higher in the patients with colorectal adenoma and cancer than in the controls, and may be used to identify subjects at high risk for colorectal cancer. PMID- 7863796 TI - Immunohistochemical analysis of P-glycoprotein expression in diverse histological types of epithelial ovarian tumors. AB - P-glycoprotein is a transmembrane protein which acts as an energy-dependent drug efflux pump for a variety of anti-cancer drugs. The mdr-1 gene which encodes P glycoprotein was successfully cloned in 1986. To investigate P-glycoprotein expression in diverse ovarian tumors, including benign, low malignant potential and malignant, immunohistochemical study was done using a monoclonal antibody (C 219). Overall, 8 out of the 59 epithelial ovarian tumors (13.6%) expressed P glycoprotein. It was noted that 5 of the 12 mucinous tumors were found to express P-glycoprotein, while none of the 31 serous tumors were immunohistochemically positive. In 10 malignant ovarian tumors, P-glycoprotein immunostaining was examined both prior to and after chemotherapy. Nine of them did not express any P glycoprotein before or after chemotherapy. However, one tumor expressed P glycoprotein after six courses of multidrug resistance-related drug administration. These findings indicate that P-glycoprotein expression is not so common in ovarian tumors, regardless of their malignant potential. Nevertheless, the results suggest a strong association between P-glycoprotein expression and certain histological cell types in epithelial ovarian tumors. It is also possible that P-glycoprotein appears as a result of chemotherapy, but such a phenomenon can not occur unless chemotherapy is administered at high doses for a long period of time. PMID- 7863797 TI - Growth and rupture of unruptured cerebral aneurysms based on the intraoperative appearance. AB - The growth and rupture of 40 cerebral aneurysms was studied in 36 patients (14 men, 22 women; were average age, 51.8 years). Aneurysms were classified into five types according to the intraoperative findings: type 1, uniformly thin, smooth surface; type 2, thin neck and thick wall, smooth surface with or without red and/or transparent portions; type 3, uniformly thick wall, smooth surface with or without red portions; type 4, thick neck, bubbled or loculated thin wall at dome with or without red and/or transparent portions; type 5, thick wall in entirety, irregular surface with or without red portions. Five were type 1, six type 2, and 12 type 3. In four of the type 2 aneurysms, turbulence could be seen at the neck. In seven of the type 3 aneurysms, red and/or transparent portions were observed in the wall. Thirteen were type 4; nine of which had a bubbled or loculated wall with or without red and/or transparent portions. Four were type 5, with scattered red portions but a thick wall. Type 1 aneurysms were 2-5 mm, most of types 2 and 3 were 3-6 mm, type 4 were 3-13 mm, and type 5 were more than 9 mm. Types 1 and 2 had few local changes in the wall, suggesting that aneurysms at this stage are stable. Type 3 is considered to be a transitional stage to type 4 from type 2. Type 4 aneurysms had some local changes within the wall including bubbles or loculi. We concluded that aneurysms exceeding 4 mm have local pathologic changes in the wall and are critical.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863798 TI - Computer simulation analysis of fracture dislocation of the proximal interphalangeal joint using the finite element method. AB - Stress is a proximal interphalangeal (PIP) joint model was analyzed by the two dimensional and three-dimensional finite element methods (FEM) to study the onset mechanisms of the middle phalangeal base fracture. The structural shapes were obtained from sagittally sectioned specimens of the PIP joint for making FEM models. In those models, four different material properties were given corresponding to cortical bone, subchondral bone, cancellous bone and cartilage. Loading conditions were determined by estimating the amount and position of axial pressure added to the middle phalanx. A general finite element program (MARC) was used for computer simulation analysis. The results of the fracture experiments compared with the clinical manifestation of the fractures justify the applicability of the computer simulation models using FEM analysis. The stress distribution changed as the angle of the PIP joint changed. Concentrated stress was found on the volar side of the middle phalangeal base in the hyperextension position, and was found on the dorsal side in the flexion position. In the neutral position, the stress was found on both sides. Axial stress on the middle phalanx causes three different types of fractures (volar, dorsal and both) depending upon the angle of the PIP joint. These results demonstrate that the type of PIP joint fracture dislocation depends on the angle of the joint at the time of injury. The finite element method is one of the most useful methods for analyzing the onset mechanism of fractures. PMID- 7863799 TI - Allergens of the house dust mite, Dermatophagoides pteronyssinus, in patients with mite allergic rhinitis: a clinical investigation by intracutaneous skin tests and nasal provocation tests. AB - To determine the allergens of mite allergic rhinitis, we studied 31 patients with mite allergic rhinitis by skin tests and nasal provocation tests (15 for skin and 16 for nasal tests) using 6 fractions of Dermatophagoides pteronyssinus (Dp) extract differing in molecular weights (15, 25, 32, 53, 95 and 190 kDMW). In skin testing, patients showed intense positive reactions to the fractions of 15, 25, 32, 95 and 190 kDMW, among which the most patients showed positive reactions to the fractions of 15 and 25 kDMW. Significant differences were found in patients' positive reactivity among each fraction and between low (15 and 25 kD) and high (95 and 190 kD) molecular weight fractions as well. In nasal provocation tests, patients showed intense positive reactions to the fractions of 15, 32, 53 and 95 kDMW, especially to the fractions of 15 and 95 kDMW. Furthermore, the insidence of positive reactions to the 15 kDMW fraction was significantly higher than that to any other fraction in the skin tests (P < 0.05). From these results, the low molecular weight fraction, 15 kDMW, is considered to be the main allergen of this mite and the high molecular weight fractions, 95 and 190 kDMW, may also be considered to be allergens of this mite. PMID- 7863800 TI - Quantitative measurement of portal blood flow by magnetic resonance phase contrast: comparative study of flow phantom and Doppler ultrasound in vivo. AB - A non-invasive method for measuring portal blood flow by magnetic resonance (MR) phase contrast was evaluated in a flow phantom and 20 healthy volunteers. In a flow phantom study, the flow volumes and mean flow velocities measured by MR phase contrast showed close correlations with those measured by electromagnetic flowmetry. In 20 healthy volunteers, the cross-sectional areas, flow volumes and mean flow velocities measured by MR phase contrast correlated well with those measured by the Doppler ultrasound method. Portal blood flow averaged during the imaging time could be measured under natural breathing conditions by using a large number of acquisitions without the limitations imposed on the Doppler ultrasound method. MR phase contrast is considered to be useful for the non invasive measurement of portal blood flow. PMID- 7863801 TI - Reliability of survey about immunization barriers in Minnesota. PMID- 7863802 TI - Should primary care physicians take care of diabetes? PMID- 7863803 TI - Efficacy of sliding-scale insulin therapy: a comparison with prospective regimens. AB - OBJECTIVE: To compare the efficacy of retroactive sliding-scale insulin therapy, proactive therapy, and a combination of the two methods in establishing glycemic control in hospitalized diabetic patients. METHODS: Medical records of 47 diabetic ketoacidosis inpatients were reviewed retrospectively. RESULTS: The sliding-scale insulin therapy group's glucose deviation score (167.4) was significantly higher than the deviation for the proactive (112.9) and combination (121.3) groups. The sliding-scale insulin therapy group also had a significantly higher median glucose value (262.5) than the proactive (199.9) and combination (221.2) groups as well as a significantly higher number of nursing shifts (0.70) in which a glucose of 250 mg/dl or greater was recorded than in the proactive (0.37) and combination (0.40) groups. The proactive group was on their treatment regimen significantly less time than the combination group (5.5 vs 10.4 nursing shifts, respectively). The proactive group was hospitalized significantly fewer days (4.4) than the combination (6.3) and sliding-scale insulin therapy (6.3) groups. CONCLUSIONS: The present study lends support to previous concerns that sliding-scale insulin therapy is less effective than preventive therapy in the management of hospitalized diabetic patients. PMID- 7863804 TI - Supportive family members of diabetic adults. AB - OBJECTIVE: Family members usually become involved during the course of care for a chronic illness. This study identified the diabetic adult's perceived supportive family member(s) and analyzed whether family participation was associated with the diabetic adults' level of metabolic control. METHODS: A telephone survey of 131 diabetic adults was conducted from a family practice residency office asking patients to identify family members participating in their diabetes care and to enumerate specific support activities. Demographic and metabolic control data were abstracted from patient records. RESULTS: Two broad categories of family participation exist. The first is the family health monitor (FHM), or internal "health expert" for the family. The other is the often distinct primary supportive family member; or "helper," defined as a family member who performs at least one supportive task in the care of the illness. Three-fourths of diabetic adults identified an FHM within their families. Eighty-seven percent of FHM's were women, usually adult daughters of diabetic women or wives of diabetic men. Forty-nine percent of diabetic women and 70% of diabetic men also identified a "helper." The most frequent helping tasks involved: dietary issues (48%), medication (23%), general support (15%) and blood sugar monitoring (9%). No relationship emerged between the presence or absence of an FHM or a helper and the level of metabolic control as measured by HbA1C level, which was categorized as "poor" in 55% of the sample. CONCLUSIONS: An FHM or some other helping family member is available to most diabetic adults in our patient population. The mere presence of an available FHM or other potential resource person is not necessarily related to a positive influence on metabolic control. PMID- 7863805 TI - Screening women in family practice settings: association between depression and smoking cigarettes. AB - OBJECTIVE: The purpose of this survey study was to test female family practice outpatients for an association between depression and cigarette smoking. METHODS: The survey consisted of demographic items including questions on smoking, and an eight-item self-report depression screening instrument. Eighty percent of the women (ages 18-91) approached agreed to participate in this study (N = 695). RESULTS: Thirty-two percent scored positive for depression and 28% smoked cigarettes. Cigarette smokers had significantly higher depression scores than did nonsmokers, and heavier smokers (> 10/day) had higher scores than did smokers of 10 or fewer cigarettes/day. CONCLUSION: There appears to be an association between smoking and depression among female family practice patients. This warrants both patient care and research attention. PMID- 7863806 TI - Information and communication about overweight in family practice. AB - OBJECTIVE: To explore whether the family doctor recognizes the problem of overweight in his patients and if this problem was addressed in the communication between patient and doctor, especially in diabetic and hypertensive patients. METHOD: During a period of three months all patients in a German family practice were weighed and measured to calculate their body mass index (BMI). Overweight patients were asked if this issue had been a topic in the communication with their doctor and if he had recommended weight reduction. In addition, the doctor was interviewed about these patients and his concept of counselling and treating obesity. RESULTS: For 75% (740/979) of all patients attending the practice, the BMI could be determined: 35% of men (116/331) and 29% of women (117/409) were were overweight, and more than half of these patients were recruited to answer a structured questionnaire. Thirty-four percent of these patients did not know their ideal weight and 51% could not remember talking about this issue with the doctor. Communication/information about this issue was ranked as good in 29% of patients and in 19% as poor. We found a moderate association between information about overweight and patients' willingness for and success in weight reduction. Only 64% of obese patients (BMI > or = 30) were considered at risk for later disease and in need of treatment by the family physician. The doctor tended to overlook overweight in hypertensive or diabetic patients. CONCLUSION: Our results suggest that more medical attention should be directed to a reliable measurement and documentation of overweight and to respective communication with overweight patients, especially when hypertension and/or diabetes is present. PMID- 7863807 TI - Inadvertent administration of DTP and DT after age six as recorded in the Vaccine Adverse Event Reporting System. AB - OBJECTIVE: Diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTP) and pediatric diphtheria and tetanus toxoids (DT) are not recommended for individuals > or = 7 years of age due to increased adverse reactions and the low pertussis case-fatality rate. Our objective was to determine if reactions to DTP and DT in individuals > or = 7 years of age were due to administration of pediatric DTP or DT instead of adult tetanus and diphtheria toxoids (Td), after adjusting for database inaccuracies. METHODS: We analyzed data from the Vaccine Adverse Event Reporting System (VAERS) reported from July 1, 1990 through March 31, 1992. Vaccine manufacturers were contacted to verify whether lot numbers indicated DTP or DT. RESULTS: According to VAERS's data, among individuals 7 years of age or older, 26 received DTP and 77 received DT. When lot numbers were compared with manufacturers' records, 8 of the 77 DT doses were confirmed; 11 had incorrect or missing lot numbers; one was a duplicate; 56 were Td; and one was neither DT nor Td. Alleged adverse reactions included fever, headache, and convulsions. CONCLUSION: Individuals > or = 7 years of age are inadvertently receiving DTP or DT and may be unnecessarily experiencing adverse reactions. The 1992 VAERS database offers opportunities to investigate hypotheses but should be interpreted with caution due to inaccuracies in reporting and duplicate entries. PMID- 7863808 TI - Prenatal and postpartum Pap smears: do we need both? AB - PURPOSE: The need to perform a Pap smear at the time of entry to prenatal care, as well as at the postpartum check-up, is questionable. A comparison of the rates of recovery of endocervical cells and the incidence of dysplasia on the prenatal and postpartum Pap smears may be helpful in determining an optimal preventive care protocol for patients who are pregnant. METHODS: Demographic and clinical data were collected from the records of 1,377 obstetrical patients at a midwest family practice residency. The yield of endocervical cells and the incidence of dysplasia was determined for both the prenatal and the postpartum Pap smears performed for this group of patients. RESULTS: In women having both exams, endocervical cells were recovered in 44.1% of prenatal Pap smears compared to 82.0% of postpartum smears. The incidence of dysplasia was 2.6% on prenatal Pap smears and 4.8% on postpartum smears. In this study population, 33% of women did not return for their postpartum check-up. CONCLUSIONS: The postpartum Pap smear is of value due to a significant yield of dysplasia. The sensitivity of the prenatal Pap test may be less than desired. Efforts directed toward increased patient compliance regarding the postpartum check-up are needed. PMID- 7863809 TI - Desirable features of qualitative research. AB - Family medicine investigators are beginning to use qualitative approaches to research questions. This paper reviews guidelines for qualitative research from several social sciences, and summarizes discussions of "standards" for qualitative research among health professionals. From these sources, the authors propose desirable characteristics of qualitative research. These include values of empathy, collaboration, service, and moral sensitivity; characteristics of clarity and coherence; techniques of participatory dialogue, triangulation, purposeful sampling, and immersion in context; and outcomes of useful knowledge and behavior effectively shared with readers. PMID- 7863810 TI - Consideration of venue and vehicle in health behavior research with adolescents. PMID- 7863811 TI - Secretion of cytokines upon allogeneic stimulation: effect of aging. AB - The aim of the present study was to investigate the in vitro mitotic response and cytokine production after allogeneic stimulation of peripheral blood mononuclear cells (PBMC) from healthy elderly subjects. Interleukin-1 (IL-1), interleukin-2 (IL-2), gamma-Interferon (gamma-IFN), and Tumor Necrosis Factor alpha (TNF-alpha) were detected in the supernatants of mixed lymphocyte cultures (MLC). The in vitro proliferative response was significantly reduced in the elderly subjects. The amount of IL-2 detected in the supernatant from cultures of cells from elderly donors was higher than for young controls, as were the production of cytokines predominantly secreted by the macrophage population (IL-1 and TNF alpha). There was no difference in the production of gamma-IFN by cells of elderly and young subjects. PMID- 7863812 TI - Serum IL-10 levels in HIV-positive subjects: correlation with CDC stages. AB - HIV-1 infection and the HIV gp120 have been shown to induce an IL-10 increase in cultured peripheral blood mononuclear cells. Furthermore, the expression of this cytokine has been reported to increase in lymphnodes of infected patients along the disease course, and a shift from the TH-1 towards the TH-0/TH-2 phenotypes (with subsequent IL-10 release) has been hypothesized to underly AIDS progression. In this study the serum IL-10 levels found in 30 HIV-negative controls and in 65 HIV-positive patients, untreated with AZT and negative for HBsAg and HCV-Ab have been compared, using a commercial, competitive ELISA method based on a polyclonal anti-IL-10 serum. With this test, HIV-positive sea showed IL-10 levels significantly higher than those found in the controls. In addition the IL-10 levels progressively increased in the subsequent CDC stages, without further changes from the stage III to the stage IV. Accordingly, patients evaluated two times in CDC stage II, with a time interval of at least one year, showed significant IL-10 increases, even more pronounced when the same patients passed from CDC stage II to stage III. Furthermore, a significant, negative correlation was observed between the circulating IL-10 levels and the patients' CD4/CD8 ratios. These data may be important from a clinical point of view since IL-10 monitoring could be considered as a surrogate marker for evaluating the disease progression. In addition, several immunological abnormalities present in HIV positive patients, such as the monocyte/macrophage impairment and the hypergammaglobulinemia could be related to the enhanced IL-10 expression. PMID- 7863813 TI - Weekly epirubicin plus low-dose interleukin-2 subcutaneous therapy in breast cancer: preliminary immunobiological results. AB - Experimental studies have shown that IL-2 may antagonize chemotherapy-induced lymphocytopenia. On this basis, we have evaluated the influence of low-dose IL-2 on lymphocyte and NK cell numbers in cancer patients treated with the anthracycline drug, epirubicin. The study included 7 metastatic breast cancer women treated with epirubicin at a dose of 25 mg/m2 i.v. weekly. IL-2 was given subcutaneously at 3 million IU/day for 6 days/week. Venous blood samples were drawn at weekly intervals, and the results were compared to those seen in 14 patients treated with epirubicin alone. Lymphocyte mean number observed on treatment was higher in patients concomitantly treated with IL-2 than in those receiving epirubicin alone, without, however, significant differences. In addition, NK cell mean number was significantly higher in patients receiving IL-2 than in those treated with epirubicin alone. These preliminary results would suggest that IL-2 may antagonize lymphocyte and NK cell declines during cancer chemotherapy with anthacyclines. Further studies will be required to confirm these results and to establish their possible influence on chemotherapy-induced tumor regressions. PMID- 7863814 TI - Resistance to recombinant alpha interferon therapy in idiopathic mixed cryoglobulinemia: reinduction of remission by natural alpha interferon both in antibody-positive and -negative patients. AB - A subset of patients treated with recombinant interferon alpha-2a (rIFN-alpha 2a) for idiopathic mixed cryoglobulinemia (IMC) developed clinical resistance to therapy after a sustained response. Neutralizing antibodies to rIFN-alpha 2a were found in the sera of three out of four such patients, and in none of the patients who remained responsive to treatment. rIFN-alpha 2a neutralizing antibodies appeared in serum samples of the former three patients 1, 5 and 6 months before evidence for clinical resistance, respectively. Antibody titres to rIFN-alpha 2a were consistently higher than those to natural interferon (nIFN). In the fourth patient with clinical resistance, neutralizing antibodies could not be detected by a very sensitive bioassay in any of several serum samples taken before and after relapse. All the four patients could be reinduced into remission by the administration of nIFN-alpha. These data indicate that mechanisms other than the production of neutralizing antibodies can mediate acquired resistance to IFN therapy. Furthermore, both antibody-related and -unrelated resistance can be overcome by switching to different species of IFN-alpha. PMID- 7863815 TI - Apoptosis in HIV infection: protective role of IL-2. AB - Peripheral blood mononuclear cells from HIV-infected subjects have been demonstrated by different methods to die by apoptosis after short time in culture. In the present study the percentages of apoptotic cells have been measured by propidium iodide staining and flow cytometry in PBMC from healthy controls (15) and HIV-infected subjects with asymptomatic (10) or advanced (15) disease, with or without anti-viral treatment. The percentage of apoptosis significantly correlated with clinical stage (CDCII: 15.85% +/- 9.17, CDCIV: 22.6% +/- 5.97, P < 0.001) and the CD4/CD8 CD3 cell ratio. R = -0.57, P = 0.012), while no differences were found in relation to AZT therapy. By adding IL-2 to the cultures the percentages of apoptosis of PBMC from HIV-infected patients were significantly reduced in all experiments. PMID- 7863816 TI - Normalization of idiopathic arterial hypertension following cancer immunotherapy with interleukin-2. AB - It is known that IL-2 cancer immunotherapy is associated with hypotension. The present study was performed to evaluate the influence of low-dose IL-2 subcutaneous therapy on blood pressure in cancer patients with idiopathic hypertension requiring hypotensive therapy. The study included 12 patients, who received IL-2 at 6 million IU/day for at least 4 weeks. Mean values of both systolic and diastolic pressure significantly decreased under IL-2 therapy, and the hypotensive agents were interrupted within 2 weeks in 10/12 patients. Moreover, 6 of them still showed normal blood pressure values without hypotensive therapy after a median follow-up of 6 months. This preliminary study would suggest that low-dose IL-2 subcutaneous therapy may normalize blood pressure values in cancer patients with idiopathic hypertension. PMID- 7863817 TI - Interaction between current smoking, leanness, and physical inactivity in the prediction of hip fracture. AB - To study the association between smoking habits and the incidence of hip fracture, adjusted for leanness and physical inactivity, a cohort study with 3 years follow-up was conducted. Subjects were 34,856 adults aged 50 years or older who attended a health screening in Nord-Trondelag County in Norway in 1984-1986 (91% of eligible subjects in 1986, n = 38,356). Of these, 421 suffered a hip fracture during the years 1986-1989. Using Cox regression models, the relative risk (with 95% confidence interval) of suffering a hip fracture for female smokers versus nonsmokers was 1.5 (1.0-2.4). These results refer to females when the female body mass index (BMI) was set at 25 kg/m2 in the female model (the mean BMI for the smoking female population in this study). Among thinner females, however, smoking had a much stronger effect. For instance, if the female BMI was set at 20 kg/m2, the relative risk was 3.0 (1.8-5.0). The relative risk of hip fracture for male smokers versus nonsmokers was 1.8 (1.2-2.9) irrespective of BMI. Smoking is associated with incidence of hip fracture in both sexes and also after adjusting for body mass index and physical inactivity (the effect of physical inactivity was adjusted for self-reported ill health because ill health was included in the model). For lean females, the association with current smoking was large, as large as if they added 10 years to their age. PMID- 7863818 TI - Fluctuation of mineral apposition rate at individual bone-remodeling sites in human iliac cancellous bone: independent correlations with osteoid width and osteoblastic alkaline phosphatase activity. AB - We investigated the determinants of bone formation at individual remodeling sites (BMUs) in cancellous bone from 8 osteologically normal, sex hormone-replete women with endometriosis. All were tetracycline double-labeled (2, 12, 2, and 4 day regime) before iliac bone biopsy. At each BMU the mineral apposition rate (MAR) was determined conventionally from the distance between label midpoints (MAR 1) and also from the distance between the mineralization front and the trailing edge of the second label (MAR 2). MAR 1 and 2 were compared with within-BMU measurements of osteoid width (O.Wi) and the activities of osteoblastic alkaline phosphatase (AP) and succinic dehydrogenase (SDH, an enzyme in the Krebs cycle), both quantitated by microdensitometry. A total of 143 BMUs were evaluated, of which 88 were satisfactory for all measurements and 132 were satisfactory for all but SDH. There was a weak correlation (r = 0.34) between MAR 1 and 2 at individual sites, with a mean difference of 0.49 micron/day (mean MAR 0.82 micron/day). The mean MAR of individual subjects tended to be either increasing or decreasing (F = 16.1, p < 0.01). In linear regressions, MAR 2 was statistically dependent on O.Wi, AP, and SDH (73% of the variance accounted for). In contrast, MAR 1 was weakly correlated with O.Wi and only 30% of its variance was accounted for by AP, SDH, and O.Wi. The variance in the MAR 2 data was inversely increased (p < 0.01) compared with MAR 1 as the number of days of bone formation represented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863819 TI - Monoclonal antibodies with selective reactivity against osteoblasts and osteocytes in human bone. AB - Monoclonal antibodies (MAb) may provide valuable tools for studying osteoblast differentiation. We therefore raised a panel of MAb reactive with cells of this phenotype using 1,25(OH)2D3-treated human trabecular osteoblast-like cells (HOBS) as the immunogen. Immunohistochemical studies on various tissues, including undecalcified cryostat sections of fetal and adult human bone, identified 11 bone cell-reactive MAb. Of these, 2 demonstrated particularly selective reactivities against osteocytes (OB/M) and osteoblasts (OB/L). These reactivities were also seen in developing bone from rat, rabbit, and marmoset. OB/L and OB/M demonstrated limited reactivity against a small number of human tissues from the extensive panel of substrates tested. Both MAb exhibited reactivity against discrete populations of cells in the large and small intestine. In addition, OB/L reacted with cells in the basal epidermis of skin and OB/M with cells in blood vessel walls. Both antibodies demonstrated reactivity against a variety of cultured osteoblast-like cell lines and other cultured cell types. These MAb may therefore provide a valuable means of studying osteoblast ontogeny. PMID- 7863820 TI - Characteristics and properties of osteocytes in culture. AB - Although the osteocyte is the most abundant among the highly differentiated cells of mature bone (osteocytes, lining cells, osteoblasts, and osteoclasts), its properties and functions are the least known and understood. Here we isolated osteocytes from mixed populations of bone cells liberated from fetal chick calvariae by alternate treatments with collagenase and EDTA. The osteocytes were removed from the bone cell populations by binding them via an osteocyte-specific antibody (MAb OB 7.3) to magnetic beads and removing the beads together with the coupled osteocytes from the population using a magnet. Isolated osteocytes were found to be highly differentiated, postmitotic cells that required their typical stellate morphology in culture. Osteocyte populations had alkaline phosphatase (ALP) activity somewhat lower than that of the osteoblast-like cell populations from which they were separated by the immunodissection procedure. On the single cell level, the ALP activity was highly variable. Parathyroid hormone (PTH) receptors were found to be present on osteocytes as well as on osteoblast-like cells, but not on fibroblast-like cells of the outer periosteum. In response to PTH, osteocytes increased their intracellular levels of cAMP, as did the osteoblast-like cells. Osteocytes appeared to be somewhat more sensitive to PTH than osteoblasts. When seeded onto dentin slices, osteocytes did not corrode the dentin surface to any appraisable degree. We therefore found no evidence to support the notion that osteocytes play a role in the calcium homeostasis through osteocytic osteolysis. Whether osteocytes play an important role in perceiving and transducing hormonal and/or mechanical stimuli remains open for future research. PMID- 7863821 TI - Glucocorticoid regulation of calcitonin receptor in mouse osteoclast-like multinucleated cells. AB - Abundant multinucleated cells (MNCs) are formed in cocultures of mouse osteoblastic cells and marrow cells in the presence of 1 alpha, 25 dihydroxyvitamin D3 [1 alpha, 25(OH)2D3], and these cells have the properties of osteoclasts (OCs). In this study using the mammalian OCs, we tried to clarify the role of glucocorticoids (GCs) in calcitonin receptors (CTR) and CT-responsive cAMP production in OCs. Dexamethasone (DEX) dose and time dependently enhanced the specific binding of [125I]salmon calcitonin (sCT). When the MNCs were preincubated with DEX for 24 h, the effect was evident at 10(-9) M and the maximum effect was obtained at 10(-7) M. The effect developed over 12-48 h at doses of 10(-9) and 10(-6) M DEX. The numbers of CTR-positive mononuclear cells and MNCs were not altered by the DEX treatment. Prednisolone and triamcinolone reproduced the DEX effect, but 17 beta-estradiol, progesterone, testosterone, aldosterone, and 1 alpha, 25(OH)2D3 did not. RU486, a GC receptor antagonist, attenuated the effect of DEX to enhance the specific binding of [125I]sCT. From a Scatchard plot analysis, DEX enhanced CTR number (212 +/- 64%) with a minimal change in the affinity to sCT. Autoradiographic studies using [125I]sCT showed that DEX enhanced the density of the grains on the tartrate-resistant acid phosphatase (TRAP)-positive MNCs and mononuclear cells, but not on other types of cells. DEX preincubation also enhanced sCT-stimulated but not prostaglandin E2- or forskolin-stimulated cAMP production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863822 TI - Analysis of type II and type X collagen synthesis in cultured growth plate chondrocytes by in situ hybridization: rapid induction of type X collagen in culture. AB - Type X collagen is produced by hypertrophic chondrocytes and serves as a highly specific marker for chondrocyte maturation. This study was designed to compare the expression of type II and type X collagen in growth plate sections and in distinct populations of chondrocytes in culture by in situ hybridization. Growth plate sections were treated with type II and type X collagen cDNA probes. Type II collagen mRNA was present throughout the growth plate but greatest in the lower proliferating and upper hypertrophic regions. In contrast, type X collagen was expressed only in the hypertrophic region. Northern analysis confirmed the specificity of the probe for type X collagen mRNA. Chick growth plate chondrocytes were separated by countercurrent centrifugal elutriation into five distinct populations and plated in serum-containing medium. These cultures were examined at varying times after plating for the expression of type II and type X collagen mRNA. At 3 h, type II collagen was present in the majority of the cells in all fractions, and approximately 15-20% of the cells expressed type X collagen mRNA. The cells expressing type X were from the hypertrophic region. At 24 h, however, nearly all cells in culture expressed type X mRNA, and there was a decrease in expression of type II collagen mRNA. Similar results were obtained in cultures in the absence of serum, and SDS-PAGE analysis of collagen synthesis confirmed the expression of type X collagen in all populations of fractionated cells at 24 h at the protein level. Type X collagen is an important marker through which cellular matruation can be evaluated in culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863823 TI - Interactions of growth hormone and parathyroid hormone in renal phosphate, calcium, and calcitriol metabolism and bone remodeling in postmenopausal women. AB - The mechanisms underlying the effects of recombinant human growth hormone (rhGH) on vitamin D, mineral, and bone metabolism are not known. We examined whether these effects are mediated by parathyroid hormone (PTH) by measuring renal phosphorus (P) and calcium (Ca) handling, serum calcitriol, and markers of bone turnover for 24 h before and 72 h after an infusion of hPTH(1-34) in eight healthy postmenopausal women at baseline and following short-term (1 week) and sustained (5 weeks) rhGH treatment. On short-term rhGH, serum phosphorus and basal TmP/GFR were unaffected, but the fall in TmP/GFR after hPTH infusion was exaggerated (integrated response: -99.2 +/- 22.3 versus -144.1 +/- 15.0 minute mg/dl, P = 0.0021). Basal calcitriol levels rose from 115 +/- 17 to 163 +/- 16 pM (P = 0.0002), but the increase in calcitriol following hPTH infusion was unaffected by short-term rhGH. The basal Ca excretion index (CEI) rose from 0.054 +/- 0.005 to 0.073 +/- 0.007 mM (P = 0.0095), but markers of bone turnover were unaffected. With sustained rhGH treatment, serum P (1.47 +/- 0.05 mM), basal TmP/GFR (4.29 +/- 0.24 mg/dl), and basal CEI (0.067 +/- 0.005 mM) were elevated compared with control values, and the PTH-induced lowering of TmP/GFR was again enhanced (-158.7 +/- 22.8 minute-mg/dl, P = 0.0021). Basal calcitriol concentrations returned to control levels (108 +/- 10 pM), but the calcitriol response to hPTH remained unchanged. Markers of bone remodeling were elevated with sustained rhGH treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863824 TI - Reduced bone mineral density in men with a previous femur fracture. AB - This study determined the areal bone mineral density (BMD) from the lumbar spine (L2-4), right distal radius and ulna, and the femoral neck, trochanter area of the femur, distal femur, patella, proximal tibia, and calcaneus of both extremities in 29 men who had a femur shaft fracture 10 years earlier. For evaluation of the patients' BMDs in the spine and distal forearm, 29 age-, weight , and height-matched normal men were also measured. Compared with normal men (mean +/- SD = 1.123 +/- 0.153), the spinal BMDs of the patients were significantly (p = 0.0054) lower (1.018 +/- 0.119, -9.3%). Distal radius and distal ulna showed no significant group differences. In patients, the mean BMD of the injured extremity (compared with the uninjured side) was significantly lower in the distal femur (-6.8%; p = 0.0000), patella (-5.4%; p = 0.0000), proximal tibia (-4.7%; p = 0.0000), and calcaneus (-2.2%; p = 0.0259). In the proximal femur, this value was at the same level (femoral neck 1.3%, NS) or higher (trochanter area 6.3%, p = 0.0002) than that in the uninjured extremity. The relative BMDs of the injured extremity did not associate with the fracture type, fracture location, age, muscle strength, follow-up time, or non-weight-bearing time but showed significant (r = 0.33-0.64) positive correlation with low pain assessment and high functional scores of the injured extremity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863825 TI - Isolation and localization of basic fibroblast growth factor-immunoreactive substance in the epiphyseal growth plate. AB - Previous research in our laboratory has shown basic fibroblast growth factor (bFGF) to be a permissive mitogen for isolated avian growth plate chondrocytes. The present study was conducted to determine whether bFGF is present in avian growth plate and, if present, to determine its localization within the tissue. Immunohistochemical studies revealed that bFGF is present in the resting proliferative and hypertrophic calcifying zones of the growth plate but is absent from the prehypertrophic zone. Basic FGF appears to be associated with the extracellular matrix of the proliferative zone, but it is predominantly intracellular in the hypertrophic and mineralizing zone chondrocytes. Partial purification of cartilage-derived bFGF was performed on crude extracts of cartilage using heparin-Sepharose affinity chromatography. The presence of bFGF in the heparin-Sepharose column fractions was confirmed by immunoblotting and radioimmunoassay. Furthermore, western blot analysis of the extracts showed multiple protein bands having bFGF immunoreactivity, in the molecular weight range 14.4-18 kD. The data support the hypothesis that bFGF has a dual role in the growth plate. In the proliferative zone it acts as a chondrocyte mitogen, whereas when released from terminal hypertrophic chondrocytes, bFGF may serve as a chemotactic signal for metaphyseal blood vessel proliferation. PMID- 7863826 TI - Comparison of radiographic absorptiometry with dual-energy x-ray absorptiometry and quantitative computed tomography in normal older white and black women. AB - Bone mineral density (BMD) of the phalanges of the hand was measured by the technique of radiographic absorptiometry (RA) in 199 older postmenopausal women previously determined to have normal BMD by dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT). The average age of the women was 66.8 +/- 4.9 years, and they were 19.9 +/- 6.7 years postmenopause. In the 54 black women, phalangeal BMD was 11.7% greater than in the 145 white women, a difference comparable to that found using DXA at the radial midshaft, the lumbar spine, and femoral neck. A correlation matrix comparing BMD measured by RA to BMD measured by DXA and QCT indicates that, in general, RA was related to the various DXA and QCT measurement sites as well as these sites were related to each other. When results for RA, DXA, and QCT obtained in our cohort of older women were compared to available reference data for peak adult bone mass, the average difference (SD units) from peak value was greatest for RA (-1.77 radius, -1.24 spine, -2.13 femoral neck, -2.34 QCT spine, and -2.71 phalanges). We conclude that RA is an acceptable measure of phalangeal BMD and that the data in our cohort can serve as reference data for older white and black women aged 55-75 years. Once the ability of RA to predict future fracture occurrence has been demonstrated, it could be rapidly deployed as a low-cost, widely available bone mass measurement technique. PMID- 7863827 TI - Age-associated changes in ultrasound measurements of the calcaneus in men and women: the Rotterdam Study. AB - Broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the os calcis were measured in a sample of 1405 persons (628 men), aged 55-93 years, from the cohort of the Rotterdam Study, a population-based study of diseases in the elderly. We studied the effect of age, body mass index, age at menopause, current use of thiazides, loop diuretics, and estrogens, smoking, and disability on SOS and BUA. Comparisons were made between ultrasound measurements and bone mineral density (BMD) measurements of the lumbar spine and proximal femur using DXA. We found a significant decline with age in SOS and BUA in men (-0.4 and -0.1 %/year, respectively) and women (-1.3 and -0.4%/year, respectively), which persisted after adjustment for body mass index. Age at menopause was not associated with SOS or BUA. Pack-years of smoking was negatively related to SOS in both sexes and to BUA in men. Severe disability was associated with lower SOS and BUA in men, but not in women. Despite the small number of exposed persons, current corticosteroid use was associated with lower BUA in men. The other risk factors examined did not affect the ultrasound measurements. We observed modest correlations between SOS or BUA, on the one hand, and BMD of the lumbar spine, on the other hand (r = 0.32-0.42). Similar correlations were found between ultrasound measurements and BMD measurements of the proximal femur. We conclude that in persons 55 years or over (1) there is a significant age-related decline of BUA and SOS, which is about three times higher in women compared with men, and (2) ultrasound measurements are not able to predict low BMD in hip or spine. PMID- 7863828 TI - Platelet-activating factor induces pseudopod formation in calcitonin-treated rabbit osteoclasts. AB - We demonstrated previously that platelet-activating factor (PAF), a potent inflammatory mediator, acts on osteoclasts to elevate cytosolic [Ca2+] and stimulate resorption. However, it is not clear whether the effects of PAF on resorptive activity are direct or indirect. In the present study, we investigated the effects of PAF on osteoclast motility. Osteoclasts were isolated from the long bones of neonatal rabbits, and cell motility and morphology were monitored using time-lapse video microscopy. Calcitonin, a hormone known to induce retraction of pseudopods and inhibit resorptive activity, was used to render osteoclasts quiescent. Within 10 minutes of calcitonin treatment (100 ng/ml, final), pronounced retraction of pseudopods was observed in 68 of 112 cells tested. When PAF (200 nM, final) was added 10 minutes after calcitonin treatment, pseudopods were evident 1 h later in 15 of 37 calcitonin-responsive cells tested. In contrast, pseudopods were evident in only 4 of 31 calcitonin-responsive cells treated with control solutions (PAF-vehicle or S-PAF, the biologically inactive stereoisomer of PAF). Pseudopod formation was quantified by measuring the planar area of pseudopods with a computer-based video analysis system. When assessed 60 minutes following PAF treatment, the pseudopod area was significantly greater in PAF-treated cells than in control cells. In some calcitonin-treated osteoclasts, PAF induced pseudopod formation when applied focally using an extracellular micropipette, consistent with a direct action of PAF. We conclude that PAF directly induces pseudopod formation in calcitonin-inhibited osteoclasts, a morphologic response indicative of osteoclast activation. PMID- 7863829 TI - Alendronate increases skeletal mass of growing rats during unloading by inhibiting resorption of calcified cartilage. AB - Loss of bone mass during periods of skeletal unloading remains an important clinical problem. To determine the extent to which resorption contributes to the relative loss of bone during skeletal unloading of the growing rat and to explore potential means of preventing such bone loss, 0.1 mg P/kg alendronate was administered to rats before unloading of the hindquarters. Skeletal unloading markedly reduced the normal increase in tibial mass and calcium content during the 9 day period of observation, primarily by decreasing bone formation, although bone resorption was also modestly stimulated. Alendronate not only prevented the relative loss of skeletal mass during unloading but led to a dramatic increase in calcified tissue in the proximal tibia compared with the vehicle-treated unloaded or normally loaded controls. Bone formation, however, assessed both by tetracycline labeling and by [3H]proline and 45Ca incorporation, was suppressed by alendronate treatment and further decreased by skeletal unloading. Total osteoclast number increased in alendronate-treated animals, but values were similar to those in controls when corrected for the increased bone area. However, the osteoclasts had poorly developed brush borders and appeared not to engage the bone surface when examined at the ultrastructural level. We conclude that alendronate prevents the relative loss of mineralized tissue in growing rats subjected to skeletal unloading, but it does so primarily by inhibiting the resorption of the primary and secondary spongiosa, leading to altered bone modeling in the metaphysis. PMID- 7863830 TI - Fractal geometry and vertebral compression fractures. AB - Cancellous bone in postmenopausal osteoporosis is characterized by widely spaced and disconnected trabeculae. These architectural changes may disproportionately increase bone fragility compared with the decrease in bone mass alone. To determine whether there is an independent architectural contribution to fracture risk, we applied fractal geometry to the cancellous bone in osteoporosis. Fractal objects have recurrent, branching patterns that are quantified by a fractal dimension D, that describes how the object fills space. Photomicrographs of transiliac bone biopsy specimens were digitized, and D was calculated from the negative of the straight portion of the slope of the log of the number of pixels containing boundary points versus the log of the pixel size over a range of pixel sizes. The results were compared with the cancellous bone histomorphometry in 31 individuals, aged 19-80 years, who were healthy before sudden death. D was inversely related to age (r = -0.72, p < 0.0001) and trabecular spacing (r = 0.87; p < 0.0001) and directly related to bone area (r = 0.86, p < 0.0001) and trabecular number (r = 0.83, p < 0.0001). We then examined 12 healthy volunteers and 12 patients with vertebral compression fractures as a result of osteoporosis who were matched for age and cancellous bone area. The patients with fractures had a 7.9% lower mean value for D (1.224 +/- 0.085 SD versus 1.329 +/- 0.125, p < 0.026). Other markers of the cancellous architecture, such as trabecular width, separation, and number, were not different between the matched groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863831 TI - Lack of evidence for rickets in the osteopetrotic rat mutation, toothless. AB - A common, but paradoxic, feature among osteopetrotic human infants is the presence of rickets. This disorder of mineralization is manifested radiographically and histologically by increased growth plate cartilage and hypertrophic cell zone thickness and excess metaphyseal osteoid and biochemically by decreased serum calcium and phosphorus concentrations. Rickets has also been reported in two osteopetrotic animal mutations, the osteosclerotic (oc) mouse and the toothless (tl) rat. Although the phenotypic expression of the rachitic lesion in the oc mouse closely resembles that in affected humans, the results of the present study show that the lesion in the tl rat does not. Compared with normal littermates, histologic and morphometric analyses of tibial growth plate cartilage in tl rats up to 5 weeks of age showed age-related increases in thickness of the proliferative cell zone and decreases in thickness of the hypertrophic cell zone that were most apparent within the central, but not lateral, regions of the growth plate and areas of acellularity and failure of chondrocytes to transform synchronously from proliferative cell to hypertrophic cell phenotypes. Femoral ash content, composition, and accretion rates did not differ from those in normal rats during the first 5 weeks of life. These findings do not support the rachitic nature of the cartilage lesion in the tl rat. Rather, a chondrodysplastic disorder is suggested, which more closely resembles the cartilage defect present in this mutation. PMID- 7863832 TI - Three-dimensional type I collagen gel system for the study of osteoblastic metastases produced by metastatic prostate cancer. AB - We developed a three-dimensional type I collagen gel cell culture system that allows coculturing of human MG-63 osteoblast-like cells and various human cancer cells. Inoculation of human PC-3 metastatic prostate cancer cells into this type I collagen gel containing human MG-63 osteoblast-like cells produced an osteoblastic-like reaction that presented as an increased number of MG-63 cells and increased density of type I collagen around MG-63 cells adjacent to inoculated PC-3 cells by microscope analysis. Under identical experimental conditions, inoculation of cell-free medium, human KLE endometrial adenocarcinoma cells, and Calu-1 lung cancer cells did not produce this blastic-like reaction. In situ hybridization documented the uniform expression of insulin-like growth factor I (IGF-I) and of urokinase-type plasminogen activator (uPA) mRNA in MG-63 and PC-3 cells separately cultured in this substrata. The uniform expression of uPA was also documented by immunocytochemistry using a monoclonal and a polyclonal antihuman uPA antibody. The relative expression of uPA was higher in PC-3 cells than in MG-63, KLE, and Calu-1 cancer cells. We conclude that this novel cell culture system may become a useful model to study the pathophysiology of the osteoblastic reaction in vitro. PMID- 7863833 TI - Long-term effects of a treatment course with oral alendronate of postmenopausal osteoporosis. AB - Several bisphosphonates are under investigation for the treatment and prevention of postmenopausal osteoporosis. Alendronate, one of these compounds, has been shown to inhibit bone turnover and induce substantial increases in bone mass, but little is known about the duration of its effects. This is considered important, keeping in mind the long half-life of bisphosphonate in bone. In this double blind controlled study, two groups of 15 postmenopausal women with spinal bone mineral density (BMD) > 2 SD below adult mean peak without vertebral fractures were randomized to receive either alendronate, 20 mg/day, or placebo for 6 months. The treatment course with alendronate significantly suppressed all indices of bone turnover (hydroxyproline, collagen crosslinks, and alkaline phosphatase activity) within 3 months, and a further slight decrease was observed in the subsequent 3 months. After treatment withdrawal, all indices of bone turnover slowly increased, and they attained the pretreatment values within 6-9 months. Lumbar spine BMD rose by 3.7% (+/- 1.7 SD) after 6 months of alendronate therapy but did not change 6 and 12 months after treatment withdrawal (4.6 +/- 2.8 and 4.7 +/- 2.6% versus baseline, respectively). In control patients a slow decrease in lumbar spine BMD was observed, but this was significant only at month 18 of the study. Femoral BMD did not significantly change in the alendronate group, but it slowly decreased in the control group at all sites of evaluation. The fractional loss became statistically significant versus both baseline and the active group by the end of the study only at the level of the femoral neck.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863834 TI - Effects of medium acidification by alteration of carbon dioxide or bicarbonate concentrations on the resorptive activity of rat osteoclasts. PMID- 7863835 TI - The central effect of electro-acupuncture analgesia on visceral pain of rats: a study using the [3H] 2-deoxyglucose method. AB - This study had the objective to understand the central effect of electro acupuncture analgesia (EAA) on visceral pain of rats. We used the method of Sokoloff's 2-deoxyglucose (2-DG) auto-radiographic quantitative analysis to observe the changes of local cerebral metabolic rate of glucose (LCMRG) in rats given electrical stimulation of greater splanchnic nerve (GSN) followed by electro-acupuncture. From the results of this study, we found that the LCMRG had a significant difference between EAA group and pain group at some structures, such as the spinal thoracic and lumbar dorsal horns (segments T6-T8, L1-L3), locus coeruleus (lc), nucleus raphe magnus (rm), nucleus reticular gigantocellularis (rgi), periaqueductal gray (PAG) and habenulae lateralis (hl) of thalanum. The results combining reports by other investigators, suggest that these local cerebral structures might be the key nuclei in EAA on visceral pain. PMID- 7863836 TI - The effect of qigong on therapeutic balancing measured by Electroacupuncture According to Voll (EAV): a preliminary study. AB - Electroacupuncture According to Voll (EAV) was used to monitor the effects of qigong practice on therapeutic balancing of subjects. In EAV the electrical conductance of the skin above individual acupuncture points is measured using low voltage and current. Diagnosis depends on measuring the relative electrical conductance and its time dependence. An important diagnostic criterion of degeneration of an organ is an indicator drop which occurs during the measurement when the conductance decreases from an apparent maximum value and then levels off. Two series of EAV measurements were made before and after healthy subjects practiced qigong. Measurements were made at 24 acupuncture points at the ends of the meridians of the fingers and toes of a subject and were made by the same operator and equipment. The subjects were asked to perform a qigong exercise of their choosing. In the first series, four subjects were examined by EAV before and after qigong exercise. Qigong exercise decreased the average EAV measured values of the four subjects in the range of -19 to -31%. Qigong eliminated indicator drops for three subjects and reduced the indicator drop by 80% for the fourth subject. In the second series, each of seven subjects was examined by EAV three times in a blind protocol so that the operator did not know whether a subject had practiced qigong before the second or third examination. Qigong exercise changed the average EAV measured values in the range of -17 to -35% for four subjects and 4 to 15% for three subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863837 TI - Effect of electroacupuncture on the level of preproenkephalin mRNA in rat during penicillin-induced epilepsy. AB - Our previous studies have shown that seizure induced by injecting penicillin (0.24 mg/2 microliters) into hippocampus could be inhibited by electroacupuncture (EA) probably via decreasing enkephalin content in hippocampus. To determine whether this change reflected the peptide synthesis, preproenkephalin (PPE) mRNA was detected in hippocampus and some other limbic structures during seizure and after EA treatment by in situ hybridization. Four hours after injecting penicillin into hippocampus, PPE mRNA levels were significantly increased by 10 folds in entorhinal cortex, subiculum, CA1 area of hippocampus, amygdaloid nucleus and piriform cortex, whereas EA treatment apparently attenuated the seizure-induced increase of PPE mRNA in the areas mentioned above. The results indicated that EA may regulate the biosynthesis of PPE in hippocampus during seizure by an alteration in gene transcription. PMID- 7863838 TI - Ga-Al-As laser irradiation inhibits neuronal activity associated with inflammation. AB - A Ga-Al-As diode system that produces low-energy red light (830 nm, 40 mW) has been used for the treatment of many kinds of pain. The mechanism of action of this new laser irradiation for analgesia was studied in anesthetized rats. The effect of laser irradiation of the saphenous nerve was studied by recording neuronal activity at the L4 dorsal root filaments after the injection of a chemical irritant, turpentine. Laser irradiation inhibited both the asynchronous firing by that was induced by turpentine and increased part of the slow components of the action potentials. Thus, the laser irradiation selectively inhibited nociceptive signals at peripheral nerves. PMID- 7863839 TI - Accurate localization of organ representation areas on the feet & hands using the bi-digital O-ring test resonance phenomenon: its clinical implication in diagnosis & treatment--Part I. AB - Accuracy of the widely used organ representation areas, currently used in different schools of foot and hand reflexology was evaluated using Bi-Digital O Ring test resonance phenomenon. Our previous study indicated that mapping organ representation areas of the tongue using Bi-Digital O-Ring Test resonance phenomenon between 2 identical substances often provided more reliable clinical information for both diagnosis and treatment than the 2 widely used, but crude, traditional schools of Chinese tongue diagnosis. This same method was applied for the mapping of the organ representation areas on the feet and hands. We succeeded in mapping the following areas on human feet: 1) Middle (3rd) toe on the sole side represents the following starting from the tip: A) Head, B) Face with eye, ear, nose, and mouth (1st Digit) C) Neck and organs within the neck (narrow band of space between 1st crease after the 1st digit and crease at the junction of the beginning of the sole); 2) 2nd and 4th toe represent upper extremities, the beginning tip being fingers and hands. The crease at the base of these toes represents the shoulder. The 2nd toe represents right upper extremity, and the 4th toe represents left upper extremity; 3) 1st and 5th toes in both the right and left feet represent lower extremities with the tip being the toes and soles of feet. The crease at the base of these toes represents the inguinal area. The 1st toe of each foot represents right lower extremity, and 5th toe represents left lower extremity. The sole of the foot is divided into the following 3 distinctive sections. 1) Upper (1st) section represents organs in the chest cavity including 2 thymus glands, trachea, 2 lungs, with the heart between them, and with the esophagus appearing as a narrow band outside of the lung near and below the 1st and 2nd toe depending upon the individual. Chest section occupies the first 1/3 to 1/5 (on a relatively long foot) of the entire sole. The boundary between the chest and G.I. system can be approximately estimated by extending the length of the entire toe or up to 25% longer to the sole, but it can be accurately determined using a diaphragm tissue microscope slide as a reference control substance. 2) Middle (2nd) section represents Gastro-Intestinal system, including lower end of the esophagus, liver, stomach, spleen, gall bladder, pancreas, duodenum, jejunum, ileum, appendix, colon, and anus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7863840 TI - Involvement of mu opioid receptors of periaqueductal gary (PAG) in acupuncture inhibition of noxious blood pressure response in rabbits. AB - Strong electric shock stimulation of the rabbit front paw elicited a pressor blood pressure response regarded as noxious response. Ligands of mu opioid receptors were microinjected into the PAG to observe their effects on acupunture inhibition of the pressor response. (1) Ohmefentanyl (OMF), a mu agonist, significantly attenuated the pressor response. Mu antagonist TCTAP greatly enhanced the pressor response. (2) Electroacupuncture (EA) significantly inhibited the pressor response, the inhibition being readily reversed by TCTAP. The response after TCTAP was significantly greater than that of the control before EA. The results suggest that noxious stimulation is able to activate the mu opioid receptor of the PAG to modulate the noxious response and EA is able to enhance the activation. PMID- 7863841 TI - Effect of artificial and human external qigong on electroencephalograms in rabbit and spontaneous electrical activity of the rat pineal gland. AB - External gigong emitted by a quartz crystal upon application of electric current was evaluated by its biological effects, such as changes in frequency-analyzed electroencephalograms (EEG) in rabbits and spontaneous electrical activity of the rat pineal gland. Physical properties of this external gigong cannot be evaluated by currently available physical means. Three types of EEG changes were produced depending on the intensity of current applied to the crystal. These changes corresponded fairly well to the dose-dependent EEG changes after intravenous administration of 5-hydroxytryptophan. A gigong-containing medal also produced similar EEG changes depending on threshold to gigong. Human gigong similarly influenced EEG. All EEG changes disappeared after pinealectomy or after application of methysergide (10 mg/kg), a serotonin antagonist. The rate of spontaneous electrical activity of the pineal gland was depressed by reorientation of the rat to the north or to the south, by gigong emitted by a quartz crystal, or by application of a gigong-containing medal. Human gigong also depressed this electrical activity. The EEG changes produced by external gigong might be caused by increased serotonin concentration in the pineal gland, since the pineal gland is responsive to gigong as well as the earth's magnetic field, which is known to inhibit N-acetyltransferase by increasing serotonin concentration in the pineal gland. Hence, the finding that current-intensity dependent EEG changes induced by quartz crystal-emitted gigong were analogous to dose-dependent EEG changes produced by 5-hydroxytryptophan might be attributed to increased serotonin levels by current-intensity-dependent inhibition of N acetyltransferase by external gigong. PMID- 7863842 TI - The dynamics of oral contraceptive use in The Netherlands 1990-1993. AB - Data from an ongoing series of surveys on contraceptive use in the Netherlands were analyzed with respect to the percentages of oral contraceptive (OC) users who annually started use, discontinued use or switched to another OC type. The surveys had been conducted between 1990 and 1993 among samples of women aged 15 49 who belonged to a survey panel. Response rates of the surveys were 89-90% and the sample sizes ranged from 4560 to 4621 women. The assessed OC use rates reflected those of the Dutch population reasonably well. Of all respondents who had used OCs during the 12 months prior to the surveys, 12-15% discontinued use within this period, mainly in order to get pregnant, 12-16% were starters and 9 14% switchers. Of all starters 37% switched to another OC type within the first 12 months after starting. Switching was mainly related to the experience of perceived side-effects and wishes for better cycle control. The results highlighted the relevance of closely monitoring the individual woman's satisfaction with her OC. Since OC use appeared in many cases to be characterized by an active seeking for the most acceptable OC type, a wide range of OC types available and the development and introduction of new types is highly relevant for tailoring contraceptive use to individual needs. PMID- 7863843 TI - Multicenter study in Hungary with a 30 micrograms ethinylestradiol- and 150 micrograms desogestrel-containing monophasic oral contraceptive. AB - Among the countries in Central and Eastern Europe, Hungary has a high oral contraceptive prevalence rate. Until recently, however, Hungarian women have not had access to combined oral contraceptives with new, third-generation progestogens. Marvelon (30 micrograms ethinylestradiol and 150 micrograms desogestrel) was first introduced in 1981 in Western Europe and has, in a number of different studies, proven an effective and well-tolerated oral contraceptive with no effect on blood pressure and a favorable lipid profile. Marvelon was introduced in Hungary in October 1991. Prior to its introduction, a multicenter study was undertaken in Hungary with Marvelon to confirm the clinical results of studies from other countries. The present study confirmed Marvelon to be an effective, well-tolerated combined oral contraceptive with no relevant effect on blood pressure. Remarkable improvements were noted, especially with regard to side-effects, in switchers from other oral contraceptives. It is concluded that Marvelon is a valuable extension of the range of contraceptive methods available in Hungary. PMID- 7863844 TI - Pregnancy, lactation and the use of silicone breast implants. AB - In the United States alone, an estimated 1-2 million women have used silicone breast implants. Many of these women are of reproductive age. Given the current controversy over the safety of silicone breast implants, medical care providers should be able to advise women if use of these implants affects the use of any of the available contraceptive methods, whether pregnancy is in any way contraindicated and/or might be associated with special complications, whether there are potential risks to the fetus and neonate, and whether breast feeding might be compromised. A review of the literature on these topics yielded very little useful information. PMID- 7863845 TI - Billings natural family planning in Shanghai, China. AB - With cervical mucus, or Billings, method of family planning, a woman learns to recognize the characteristics of her cervical mucus that identify the fertile phase in her menstrual cycle. She and her partner abstain from sexual activity during a period from the first indication of mucus until four days after the mucus peak day, which includes ovulation. They also abstain during menses, because mucus can be confused with menstrual bleeding. This method of family planning is used widely, worldwide, by couples seeking a natural, reliable method of family planning. Between July 1988 and May 1990, 688 couples of child-bearing age, most of whom were parous, used the Billings method for contraception. Five hundred and fifty of these couples used the method for more than 12 months. Efficacy, continuation rates, and discontinuation rates were analyzed using life table analysis for 10,175 woman-months of data collected. The net cumulative discontinuation rates per 100 women at 12 and 18 months were 19.85 and 34.58, respectively, resulting in continuation rates of 80.15 and 65.42. The discontinuation rates per 100 women for method-related reasons at 12 and 18 months were 1.61 and 2.84, respectively, while the discontinuation rates for unintended pregnancy were 1.02 and 1.18. During the study, 67 subjects volunteered to have vaginal smears taken from the upper part of the vaginal wall for cytologic examinations, and among them serum and urine LH levels were measured in 10 subjects and urinary estrogen and progesterone were assayed in 35 cases. These tests related other indications of the menstrual cycle to the ability of the women to judge ovulation by cervical mucus. Our research suggests that further investigation of the Billings method is warranted and that careful planning and organization are needed to disseminate the method more broadly. PMID- 7863846 TI - Copper intrauterine contraceptive device and pregnancy rate. AB - Between August 1983 and August 1992, 1995 women aged 20-43 years were fitted with 2736 copper intrauterine contraceptive devices (MLCu250, MLCu375, Nova-T, Gravigard, Anticon). Insertion of the IUD was performed during menstruation by a skilled team of gynecologists. The women were instructed to self-check the IUD tail after each menstrual period. All the women were examined after one month and were followed-up every six months. The 1995 acceptors accumulated a total use of 69,350 months. During this period 39 accidental pregnancies occurred (Pearl Index 0.62, cumulative net pregnancy 1.95 per 100 women). Thirty-six pregnancies were intrauterine and three were ectopic. Most of the accidental pregnancies occurred during the first 12 months of use. The pregnancy rate of IUD users was negatively correlated with age. It is concluded that fitting the Cu-IUD intramenstrually, teaching the user to self-check herself and having frequent re-examinations seems to decrease the pregnancy rate in Cu-IUD users. PMID- 7863847 TI - The morphologic changes of endometrial spiral arterioles in IUD-induced menorrhagia. AB - To investigate the relationship between IUD-induced menorrhagia and spiral arteriolar function, we examined the endometrium under light and electron microscope on samples obtained within 24 hours after the onset of premenstrual spotting. These samples included an IUD bleeding group (20 cases), an IUD non bleeding group (20 cases) and an IUD non-user group (10 cases) as controls. Compared with the IUD non-user group the degenerative changes of spiral arteriolar wall were more severe and dilation of the spiral arteriolar lumen was more obvious, especially in the spongeous layer. In the IUD non-user group these changes were mild, suggesting that IUD-induced menorrhagia might be correlated with poor contractility of spiral arterioles in the spongeous layer. PMID- 7863848 TI - Mechanical devices for interval laparoscopic tubal sterilization in previous IUD users. AB - This retrospective analysis was conducted to determine whether IUD users are good candidates for laparoscopic sterilization using the tubal ring and the Filshie clip. The data set used for the analysis came from international multicenter clinical trials involving 1235 women who were sterilized by the tubal ring and 1892 women sterilized by the Filshie clip. Results indicate that former IUD use is not associated with an increased risk of surgical injuries, including uterine perforation, major complications, or postoperative infections, for either of these tubal occlusion techniques. The risk of a sterilization procedure ending in technical failure (defined as switching to laparotomy and/or a tubal occlusion technique not originally planned) among tubal ring cases was greater for former IUD users than for non-IUD users. However, this may be related to a center effect. Nine of the 10 ring cases with technical difficulties were successfully switched to electrocoagulation, and the operator did not have to resort to an unintended laparotomy. The incidence of surgical difficulties among the Filshie clip cases was also higher in former IUD users, but all of these difficulties were safely overcome without changing the tubal occlusion method. These findings lead us to believe that, in general, a woman's IUD use should not generally be a reason for an experienced service provider to hesitate in performing an interval laparoscopic sterilization using a mechanical tubal occlusion technique. PMID- 7863849 TI - Reliability of light trap sampling for Anopheles fluviatilis, a vector of malaria. AB - The utility of light traps for sampling Anopheles fluviatilis, the major malaria vector in the hill tracts of Koraput district, Orissa, was assessed. A modified version of the CDC miniature light trap was used in the study. The data generated from light trap collections were analysed and compared with daytime resting, man biting and night resting collections carried out in parallel. The number per trap recorded in cattle sheds was significantly higher than that recorded in human dwellings. A similar pattern was observed in hand catches of indoor resting population though the difference was not significant. The density recorded from light traps over time was found to have a significant positive linear association with corresponding indoor (r = 0.625; p = 0.0019) as well as outdoor (r = 0.603; p = 0.0029) diurnal resting densities. The proportion with different gonotrophic stages varied significantly between different types of collections. The age structure of A. fluviatilis did not differ significantly with the types of collection. As the light trap catches reflect seasonal fluctuations in the diurnal resting collections, they can justifiably be used in monitoring the relative density of A. fluviatilis in the place of cumbersome hand catch methods. Other uses of light traps are also discussed. PMID- 7863850 TI - Plasmodium falciparum: the population structure of mature gametocyte cultures has little effect on their innate fertility. AB - In vitro cultured Plasmodium falciparum gametocytes were fed to Anopheles gambiae (G3) mosquitoes to identify parasite population characteristics useful for predicting successful mosquito infections. Parameters were collected from an initial study of 90 infections over a two year period and a second study of 55 infections over 12 weeks. Parasite isolate/clone was identified as the most reliable predictor of gametocyte infectiousness. Parameters such as gametocyte age structure (stage IV:V ratio), exflagellation rate and macrogametocyte maturity were not reliable for predicting infectiousness but were useful for monitoring overall culture maturity. Other variables such as gametocyte density, chronological age of the culture at the time of feed, gametocyte sex ratio, asexual parasitemia, and mixing cultures before mosquito feeding were not predictive. Thus, if a reliable parasite isolate or clone is used, there is no need to measure other characteristics of in vitro gametocyte populations because these will not significantly improve one's ability to predict oocyst infection rates. PMID- 7863851 TI - A survey of Schistosoma mansoni induced kidney disease in children in an endemic area of Machakos District, Kenya. AB - The association between Schistosoma mansoni infection and kidney lesions was investigated in school children selected from three primary schools in Machakos District, Kenya, namely Miu (n = 159), Kitengei (n = 160) and Misuuni (n = 99) schools. The children were examined parasitologically for S. mansoni infection, clinically for enlargement of the liver and spleen, and biochemically for proteinuria and serum and urine creatinine. High prevalences of S. mansoni infection, ranging from 84-96%, were seen in all the schools, but the geometric mean intensity of egg excretion varied, being relatively low in Misuuni (31 eggs/g), medium in Miu (182 eggs/g) and high in Kitengei (413 eggs/g). The prevalence of pathological proteinuria (> or = 200 mg/l) in the schools ranged from 10.1% in Miu to 28.8% in Kitengei. No difference in the levels of proteinuria was noted between age or sex groups. No association between intensity of infection and pathological proteinuria was observed in any of the schools, nor was any correlation between organomegaly and proteinuria observed. However, significant correlations between malaria and organomegaly (p < 0.001) and between malaria and proteinuria (p < 0.05) were observed when pooling data from all schools. These findings suggest that S. mansoni induced nephrotic syndromes are not common in children from this highly endemic area of Kenya. PMID- 7863852 TI - Mortality of under-fives in a rural area of holoendemic malaria transmission. AB - From January 1992 to December 1993, a total of 361 births and 243 deaths were recorded by village reporters in five villages in Muheza District, north eastern Tanzania. Among those aged less than one year 48 deaths were recorded, giving an infant mortality rate of 133 per 1000 live births (95% CI 97.9-168.0). There were 42 deaths among the censused population of 845 children aged 1-4 years (24.8/1000/year, 95% CI: 17.4-32.3). Verbal autopsy questionnaires were administered to parents or close relatives of 83 of the dead infants and children. From analysis of these, 30 of the deaths were tentatively attributed to malaria. The results are discussed in relation to other studies in East and West Africa and to the prospects for reducing mortality by use of insecticide impregnated bednets. PMID- 7863853 TI - Pharmacokinetics of melarsoprol in uninfected vervet monkeys. AB - The level of the trypanocidal drug melarsoprol was determined in serum and cerebrospinal fluid (CSF) of six healthy vervet monkeys after intravenous application of the drug following a standard treatment schedule and a recently suggested alternative protocol. The maximum serum levels measured were about 3 micrograms/ml. A three-compartment model was used to analyze the serum data. The mean residence time calculated for melarsoprol in serum was 18 h, the volume of distribution was 3.6 l/kg and the clearance was 3.5 ml/min*kg. In the CSF the drug levels were generally very low, not exceeding 55 ng/ml, and the adaptation of the drug levels was found to be very low. The comparison of the drug concentrations required to eliminate trypanosomes in vitro and the drug concentrations reached in the CSF during treatment revealed that the latter might be insufficient in some cases to eliminate all trypanosomes from this site. The peak serum levels during alternative application of the drug were lower compared to those during empirical treatment. No evidence for drug cumulation in the body was found. The results of this study are compared with recent pharmacokinetic data from human patients, and discussed in the context of the problem of relapses and reactive encephalopathy occurring after treatment of sleeping sickness. PMID- 7863854 TI - Using cuticular hydrocarbon composition to elucidate phylogenies in tick populations (Acari: Ixodidae). AB - Cuticular hydrocarbon composition is used to explain hypothetical phylogenies among sympatric and allopatric populations of Amblyomma cajennense, A. variegatum and Ixodes ricinus tick species. The method proposed here uses a parsimony analysis of endemicity by disjunct biochemical data (PAEDB) based in the pattern of cuticular hydrocarbons. The advantage of our approach is that information contained in fragments that are not conserved in all the individuals of a populations need not be discarded, and that only patterns of presence/absence are used. In such a way, PAEDB methodology provides a system which traces the pathway of a definite compound through populations, together with data of genetic relationships among specimens. PMID- 7863855 TI - The median age of primary malaria infection in an Amazonian community: probit analysis of cross-sectional data. PMID- 7863856 TI - In vitro development of suramin-resistant clones of Trypanosoma evansi. AB - By exposure to gradually increasing concentrations of suramin in modified Baltz's cell free culture system, suramin-resistant clones of Trypanosoma evansi, JGcl 160, JX-lcl-160 and ZJcl-140, were derived from suramin-sensitive clones JGcl, JX lcl and ZJcl, respectively, over a period of 550 days. In vitro tests showed that the IC50 values of JGcl-160, JX-lcl-160 and ZJcl-140 were 358.5, 412.3 and 246.4 micrograms/ml respectively, which were 1792.5, 1874.1 and 1760.0 times higher than those of their parent clones. The values for the curative dose CD100 for intact mice infected with JGcl-160, JX-lcl-160 and ZJcl-140 were 80, 120 and 30 mg/kg respectively, which were 5.3, 8.0 and 3.0 times higher than those of each parent clone. The CD100 values for immunosuppressed mice infected with these clones were 250, 300 and 100 mg/kg, respectively, which were 3.1, 2.5 and 3.3 times higher those for intact mice infected with the same clones. PMID- 7863857 TI - [Influence of extracorporeal shock wave lithotripsy (ESWL) on renal function assessed by 99mTc-DMSA scintigraphy: comparative analysis between ESWL and percutaneous nephroureterolithotripsy (PNL)]. AB - 99mTc-DMSA renal scintigraphy was utilized to investigate the influence of ESWL on renal function in comparison with that of PNL. In the beginning, the reproducibility of renal uptake rate by the scintigraphy was examined in eleven healthy volunteers under both non-diuretic and diuretic states. The renal uptake rate was shown to be sufficiently reproducible in the same person in the two different trials. However, the differences and the standard deviations were shown to be a few percentages, which were not statistically significant. Changes in the repeated renal uptake rate seem to indicate not only changes of renal function with the treatment but also some technical errors. Herein, to investigate changes in renal function of the therapeutic side, the uptake ratio rate (rate of uptake rate in the therapeutic side/uptake rate in the contral lateral side) was utilized instead of uptake rate. Renal scintigraphy was carried out in 48 patients with unilateral renal stones before and after ESWL or PNL monotherapy or the combined ESWL and PNL therapies. Within one week of treatment, the uptake ratio rate significantly decreased in patients with PNL or the combined ESWL and PNL, although DMSA uptake rate in the therapeutic side did not significantly changes. Neither renal uptake rate nor uptake ratio rate significantly changed after ESWL treatment. There was no significant difference in changes of uptake ratio rate between Siemens Lithostars Plus and the improved Dornier HM-3 lithotriptors. This study indicated that ESWL monotherapy did not affect the uptake ratio rate, although PNL monotherapy and the combined ESWL and PNL therapies may affect the uptake ratio rate to some extent. PMID- 7863858 TI - [Extracorporeal shock wave lithotripsy monotherapy for upper urinary tract stones using the Dornier lithotriptor MFL5000]. AB - A total of 345 cases of upper urinary tract stones (188 renal and 157 ureteral stones) were treated by extracorporeal shock wave lithotripsy (ESWL) monotherapy using the Dornier lithotriptor MFL5000. Of these cases 294 (85.2%) had stones less than 20 mm in length. A double-J ureteral stent was placed in 40 cases of renal stones and 8 ureteral stones due to large stone burden or failure of in situ ESWL for impacted stones. Epidural or spinal anesthesia was necessary in 32 cases to maximize the generator voltage or to prevent intractable pain. The number of ESWL sessions and shock waves increased in accordance with the stone size, with an average of 1.6 and 4442, respectively. Multiple sessions were required in 68 cases of renal stones (36.2%) and 59 of ureteral stones (37.6%). With a 3-month follow-up, the stone-free rate was 60.5% for renal stones and 89.4% for ureteral stones, with the overall stone-free rate of 74.7%. Including the cases with residual fragments less than 4 mm, ESWL monotherapy was successful for 86.4% of renal stones and 93.6% of ureteral stones, achieving the overall success rate of 89.9%. No serious complications related to ESWL were observed. Four cases of impacted ureteral stones underwent ureteroscopic extraction or open ureterolithotomy for fragment removal. ESWL monotherapy using the Dornier MFL5000 is an effective and noninvasive method of treating upper urinary tract stones. Satisfactory fragmentation and clearance can be achieved with multiple sessions even for large or impacted stones, but alternative procedures may be necessary to salvage fragments of impacted stones. PMID- 7863859 TI - [Study on E-cadherin expression in relation to invasion and metastasis in urothelial cancer patients]. AB - E-cadherin expression was investigated in 30 patients with urothelial cancer (bladder; 27, ureter; 2, urethra; 1) by an immunohistochemical method. Twelve out of 22 patients with strong and homogeneous expression of E-cadherin (preserved) had grade 1 tumors, while all 8 patients with heterogeneous, weak and homogeneous, or lost expression of E-cadherin (reduced) had grade 2 or grade 3 tumors. Only 2 out of 22 patients with preserved expression had invasive tumors (> or = pT2), whereas 6 out of 8 patients with reduced expression had invasive tumors (p = 0.002). Three out of 4 patients with metastasis had reduced expression and 2 of them died. These findings suggest that urothelial tumors with reduced expression of E-cadherin have high grade and high stage, and E-cadherin expression could be one of the prognostic factors. PMID- 7863860 TI - [Asymptomatic pheochromocytoma: a report of three cases]. AB - We present three cases of asymptomatic pheochromocytoma treated at Sumitomo Hospital. They had no hypertensive episode. The tumors of Case 1 and Case 3 were incidentally detected by abdominal ultrasonography at the Health Screening Center of Sumitomo Hospital. The tumor of Case 2 was incidentally detected by abdominal ultrasonography in the health examination of his company. Case 1. A 49-year-old male was hospitalized in Apr. 1992 because of further examination of a right adrenal mass. He underwent right adrenalectomy and its histological examination revealed pheochromocytoma. Case 2. A 45-year-old male was referred to our department for further examination of a left adrenal mass in Aug. 1993. On admission, endocrinological examination was almost normal. He underwent surgical removal of the tumor and its histological examination revealed pheochromocytoma. During the operation, blood pressure and pulse rate were almost unchanged. Case 3. A 51-year-old female was hospitalized in Oct. 1993 because of further examination of a left retroperitoneal mass. She underwent surgical removal of the tumor and its histological examination showed paraganglioma. PMID- 7863861 TI - [A case of endocrinologically active retroperitoneal ganglioneuroma]. AB - A 27-year-old female complained of right upper abdominal pain. Computed tomography revealed a retroperitoneal tumor located between the right kidney and the vena cava. The preoperative value of noradrenaline in urine was high, 221.1 micrograms/day. She underwent surgery and the resected tumor was 330 g in weight and 8 x 6 x 4 cm in size. Histopathological diagnosis was ganglioneuroma. Retroperitoneal ganglioneuroma is rare and only 82 cases including our case have been reported in Japan, in recent years, adult cases are increasing in number. Endocrinological abnormalities were observed in 9 cases. Although six of the 9 patients were younger than 5 years old, the others were adults. These adult patients had no endocrinological symptoms. PMID- 7863862 TI - [Two siblings with 2,8-dihydroxyadenine urolithiasis]. AB - We treated two children with 2,8-dihydroxyadenine urolithiasis for over 7 years. The male prepositus was admitted to the hospital because of anuria when he was 10 months old. Bilateral urinary stones had caused the anuria. The stones were 2,8 dihydroxyadenine and his APRT activity was low. He has been treated with about 5.0 mg/kg/day of allopurinol without purine diet restriction. His sister, 3 years old at that time, also was found to have a renal stone. She has been treated with about 3.3 mg/kg/day of allopurinol without restricting purine. The allopurinol therapy without purine-restriction resulted in normal growth of both children with neither the recurrence of stone nor renal impairment. PMID- 7863863 TI - [Bellini duct carcinoma treated with partial nephrectomy: a case report]. AB - We report a rare case of collecting duct carcinoma of the kidney (Bellini's duct carcinoma). A 37-year-old woman visited our hospital with a chief complaint of asymptomatic hematuria. We suspected right renal pelvic tumor from the detection of round filling defects in the upper calyces of the right kidney by image diagnoses. A ureteroscopic biopsy revealed a low grade renal cell carcinoma. Therefore, she received right partial nephrectomy immediately. Histological examination of the surgical specimen showed a highly differentiated adenocarcinoma with papillary proliferation besides the collecting duct epithelium. With the results of the strongly positive patterns of immunohistochemical staining with high molecular cytokeratin and peanut aggulutinin, the tumor corresponded to the distal nephrons. Therefore we made the diagnosis of Bellini's duct carcinoma. She had been alive without evidence of metastases for one year after surgery. PMID- 7863864 TI - [Bladder hernia associated with bladder diverticulum in a female]. AB - A 77-year-old woman with a previous history of pelvic fracture had suffered from recurrent cystitis. In the excretory urography, post-void upright film revealed the bladder hernia associated with the bladder diverticulum. Transurethral incision and fulguration of the bladder diverticulum and left inguinal herniography was performed. There has been no recurrence since then. PMID- 7863865 TI - [A case of carcinomatous meningitis from transitional cell carcinoma of the urinary bladder]. AB - We report a case of carcinomatous meningitis from transitional cell carcinoma of the urinary bladder. A 70-year-old man with invasive bladder cancer and multiple pulmonary metastases received 3 courses of systemic M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy, after which the primary tumor and pulmonary metastases diminished in size and number. During the 4th course of chemotherapy, he complained of nausea, headache, diplopia, and neck stiffness. Computer tomographic (CT) scan of the brain showed no evidence of parenchymal metastases, cerebral hemorrhage, or infarction. Cerebrospinal fluid examination revealed an increase in cells along with elevated protein and depressed glucose concentrations, but no malignant cells were identified. He died two weeks after the onset of neurological symptoms. Autopsy revealed numerous tiny metastatic lesions in the leptomeninx, so called carcinomatous meningitis, without parenchymal metastases in the brain. Although metastases to the central nervous system from transitional cell carcinoma of the bladder, especially carcinomatous meningitis rarely have been reported, this unusual complication will be seen more frequently with the development of more effective systemic chemotherapy such as M-VAC. PMID- 7863866 TI - [A case of primary signet ring cell carcinoma of urinary bladder]. AB - A 72-year-old female patient presented to our clinic with the chief complaint of gross hematuria and urinary frequency on September 6, 1990. Cystoscopic examination revealed a thumb's head size nonpapillary tumor. The tumor was located adjacent to the orifice of the left ureter. Histological findings of the tumor by transurethral resection (TUR) indicated transitional cell carcinoma with partial signet ring cell carcinoma. No other malignant findings in any other organs including the gastrointestinal tract were noted. Total cystectomy was performed and Indiana pouch was constructed. Histopathological staging was pT1 N0 M0. The patient died of multiple metastasis of the signet ring cell carcinoma on June 22, 1992. This is the thirty-second case of signet ring cell carcinoma of urinary bladder reported in the medical literature in Japan. We investigated 19 alive or unknown cases as follow up and briefly discussed the treatment and outcome of the primary signet ring cell carcinoma of the urinary bladder. The outcome appeared to be somewhat better than previous reports. Total cystectomies were performed in 18 of the 32 cases (56.3%). As noted in past reports, the treatment of our patient consisted of total cystectomy. Twenty-two patients died of signet ring cell carcinoma. Recurrence to the pelvic area was observed in 18 of the 22 (81.8%) patients who died. Because of this high rate of recurrence, we recommend a thorough assessment of the pelvic area of the patients diagnosed with signet ring cell carcinoma of urinary bladder. PMID- 7863867 TI - [Asymptomatic synchronous bilateral granulomatous orchitis--a case report]. AB - A case of asymptomatic synchronous bilateral granulomatous orchitis in a 79-year old male patient is described. He was diagnosed with asymptomatic microhematuria, and referred to our outpatient clinic. In the physiological examination, there were stone-hard indurations in his bilateral testes. There were multiple hypoechoic areas in the scrotal ultrasonography. Bilateral testicular tumor was suspected. However, histological findings after bilateral orchidectomy revealed granulomatous orchitis. Abdominal computed tomography revealed swelling of the paraaortic lymph nodes postoperatively. However no malignant origin was detected. Differential diagnosis between testicular tumor and granulomatous orchitis is very difficult in any examination except by histological findings. Conservative therapy is usually not effective, and most cases are treated by orchidectomy. Bilateral cases of this entity are relatively rare, but in young cases, it is necessary to distinguish the granulomatous orchitis from the testicular tumor before surgical intervention. PMID- 7863868 TI - [Clinical statistics on patients operated at the Department of Urology, Kaizuka Municipal Hospital during ten years (from 1983 to 1993)]. AB - A statistic survey was made on the patients undergoing operations between July, 1983 and June, 1993. The total number of patients was 1780, comprising 1469 males and 311 females. The most frequent organ was the prostate with 526 cases (29.6%), followed by 415 (23.3%) penile and scrotum cases, and 290 (16.3%) bladder cases. Major operations were transurethral resection of prostate (418 cases) and bladder tumor (191 cases). PMID- 7863869 TI - [Clinical study of a new injectable cephem, FK037, for acute bacterial prostatitis]. AB - FK037, a new injectable cephem antibiotic, was administered in the treatment of 13 acute bacterial prostatitis (mean age 53.5, range 30-79), and its effectiveness and safety were evaluated. The human prostatic fluid (PF) concentration of FK037 on 7 specimens 1 hour after 1 g i.v.d., was in the range of 0.87-7.47 micrograms/ml (mean +/- SD, 3.43 +/- 2.23 micrograms/ml), whereas, the serum concentration averaged 45.3 +/- 2.88 micrograms/ml, the ratio of PF/serum consequently being 0.08 +/- 0.05. In the clinical study, 1g of FK037 was administered to 13 patients by i.v.d. twice a day for 7-9 days. Bacteriological eradication on expressed prostatic secretion (EPS) was obtained for all clinical isolates which included 11 strains of Escherichia coli (MIC < or = 0.05 microgram/ml), 2 of Enterococcus faecalis, and each one of Staphylococcus aureus and Morganella morganii. Symptomatical cure was 100% in all cases. As for safety profile, no side effects were noted. In laboratory values, slight elevation of transaminase were detected in 3 cases, but they were transient and returned to normal 1-2 weeks after completion of the therapy. We conclude that FK037 is highly effective in the treatment of acute bacterial prostatitis, and is well tolerated in comparison with other relative antimicrobials. PMID- 7863870 TI - H. Joachim Burhenne Lecture. Common areas of interest between interventional biliary radiology and endoscopy. AB - Therapeutic biliary endoscopy is a more recent subspecialty than interventional biliary radiology, and much has been learned from the pioneering work of interventional radiologists. The areas of interest to biliary radiologists and biliary endoscopists are largely identical. The common bile duct can be approached either by the antegrade percutaneous transhepatic approach or by the retrograde endoscopic transpapillary route. In most cases, endoscopy is the treatment of choice because of its lower risk. A new era in therapeutic endoscopy began with the invention of endoscopic papillotomy in 1973 by Classen and Demling in Germany [1] and Kawai et al. in Japan [2]. This technique made access to the hepatobiliary and pancreatic ductal systems possible, and endoscopic papillotomy has replaced choledochotomy for the treatment of bile duct stones in many centers. Endoscopic or radiologic treatment can entirely replace surgical management. The radiologic approach is advantageous via the endoscopic route when a patient has residual stones in a T tube or intrahepatic stones that lie proximal to a stricture. For patients who have had abdominal surgery and in whom access to the papilla is sometimes impossible because of a long afferent jejunal loop, radiologic therapy is suitable. They also can be treated by the rendezvous approach, whereby the radiologist feeds a guidewire through the papilla into the duodenum and the endoscopist then accesses the bile duct in a retrograde fashion. Calculous disease and ductal stenoses are the main indications for endoscopic therapy; these and other conditions of the biliary tract will be discussed here. PMID- 7863871 TI - Pathogenesis of atherosclerosis. AB - Cardiovascular disease is the leading cause of death in the United States. According to numbers compiled by the American Heart Association, nearly one of every two Americans dies of cardiovascular disease. For example, in 1987, 976,706 (46%) of the estimated 2,127,000 deaths recorded in the United States were attributable to diseases of the heart and blood vessels [1]. Most of these deaths can be attributed to atherosclerosis and its ensuing complications. The pathogenesis of atherosclerosis is not completely understood. Nevertheless, the purpose of this review is to provide an overview of how an atherosclerotic lesion might develop on the basis of our current understanding. This overview will focus on one hypothesis of atherosclerosis development, the modified response-to-injury hypothesis. Several additional hypotheses will be described briefly. These descriptions can serve as a framework on which researchers can build a more complete understanding of the processes involved in this complicated, multifactorial disease. PMID- 7863872 TI - Hypercoagulability and the hypercoagulability syndromes. AB - Hypercoagulability is a state in which an alteration of the blood shifts the hemostatic balance toward excessive platelet/fibrin deposition leading to arterial and/or venous thrombosis [1]. Although the concept of hypercoagulability has been recognized clinically for more than a century, in recent years a number of specific disorders have been define, diagnostic tests developed, and treatment regimens improved. The currently recognized disorders are generally classified as primary or secondary states, although some of the primary conditions may develop as a result of other disorders (Table 1). The primary disorders generally result from abnormalities of proteins in the coagulation or fibrinolytic systems. Although the number of secondary conditions is much greater, generally these syndromes are not as precisely defined on a molecular basis. Secondary hypercoagulability syndromes are subclassified into abnormalities of platelets, coagulation and fibrinolysis, and blood vessels and rheology (Table 1). While the prevalence and clinical significance of hypercoagulability are becoming increasingly apparent to physicians in general, this pathologic state is an especially practical concern to vascular interventionalists, as hypercoagulability is an important cause of early thrombosis after otherwise uncomplicated arterial interventional procedures. The purpose of this review is to describe the clinical presentation, diagnosis, and treatment of the hypercoagulability syndromes most likely to be encountered by the interventional radiologist. PMID- 7863873 TI - The hamartomatous polyposis syndromes: clinical and radiologic features. AB - Most radiologists are familiar with the clinical and radiologic features of the familial adenomatous polyposis syndromes [1]. The hamartomatous polyposis syndromes occur less frequently, however, and their radiologic and clinical manifestations are not as well known. This group of syndromes includes Peutz Jeghers, multiple hamartoma, juvenile polyposis, Cronkhite-Canada, and Bannayan Riley-Ruvalcaba. The predominant gastrointestinal lesion in these diseases is some form of hamartomatous polyp. The term hamartoma implies a nonneoplastic tumor or tumorlike condition composed of tissue elements normally present in the particular area [2]. In many of these syndromes, it is now recognized that hamartomatous polyps of the gastrointestinal tract coexist with adenomas and that adenomas may develop within hamartomatous polyps. Either situation may contribute to the frequent association of alimentary tract adenocarcinoma that occurs in most of these syndromes. Various types of benign mucocutaneous lesions are common and often lead to the correct diagnosis. Of greater importance is the frequent occurrence of other extraintestinal manifestations, including several forms of malignant disease. Because of this frequent association with both gastrointestinal and nongastrointestinal malignant tumors, early and accurate diagnosis of these syndromes is essential. Meticulously performed double contrast studies are the preferred radiologic procedures for the diagnosis of gastrointestinal polyps in all of these diseases. PMID- 7863874 TI - Aneurysmal bone cyst: concept, controversy, clinical presentation, and imaging. AB - The aneurysmal bone cyst is the result of a specific pathophysiologic change, which is probably the result of trauma or a tumor-induced anomalous vascular process. In approximately one third of cases, the preexisting lesion can be clearly identified. The most common of these is the giant cell tumor, which accounts for 19-39% of cases in which the preceding lesion is found. Other common precursor lesions include osteoblastoma, angioma, and chondroblastoma. Less common lesions include fibrous dysplasia, fibroxanthoma (nonossifying fibroma), chondromyxoid fibroma, solitary bone cyst, fibrous histiocytoma, eosinophilic granuloma, and even osteosarcoma. Interestingly, some of the controversy surrounding this lesion may be the result of a change in how the lesion was defined by Lichtenstein in 1953, when intramedullary lesions were added to the previously described juxtacortical (superficial) lesions. Members of the AFIP have suggested that many of the intramedullary lesions in which no previous lesion can be identified may represent giant cell tumors of bone. Their similarity to proved giant cell tumors in skeletally immature patients can be striking and seems more than coincidental. Appropriate treatment of an aneurysmal bone cyst requires the realization that it results from a specific pathophysiologic process, and identification of the preexisting lesion, if possible, is essential. Clearly an osteosarcoma with superimposed secondary aneurysmal bone cyst change must be treated as an osteosarcoma, and giant cell tumor with secondary features of aneurysmal bone cyst would be expected to be more likely to recur locally. The vast majority (approximately 80%) of patients presenting with aneurysmal bone cystlike findings are less than 20 years old. More than half of all such lesions occur in long bones, with approximately 12-30% of cases occurring in the spine. The pelvis accounts for about half of all flat bone lesions. Most patients present with pain and/or swelling, with symptoms usually present for less than 6 months. The imaging appearance of aneurysmal bone cyst reflects the underlying pathophysiologic change. Radiographs show an eccentric, lytic lesion with an expanded, remodeled "blown-out" or "ballooned" bony contour of the host bone, frequently with a delicate trabeculated appearance. Radiographs may rarely show flocculent densities within the lesion, which may mimic chondroid matrix. CT scanning will define the lesion and is especially valuable for those lesions located in areas in which the bony anatomy is complex, and which are not adequately evaluated by plain films. Fluid-fluid levels are common and may be seen on CT scans and MR images.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863875 TI - Interventional radiology of the chest: image-guided percutaneous drainage of pleural effusions, lung abscess, and pneumothorax. AB - Percutaneous catheter drainage of intrathoracic collections has developed as a natural extension of similar interventional radiologic procedures in the abdomen. The advent of CT and sonography, which allow detection and characterization of pleural and parenchymal collections, combined with advances in drainage catheter design and interventional techniques, have made imaging-guided management of intrathoracic collections a safe and effective alternative to traditional surgical therapy. This article begins with a review of the etiology, pathophysiology, diagnosis, and treatment of parapneumonic pleural effusion, which remains the most common indication for image-guided percutaneous drainage. Subsequent sections consider issues related to percutaneous drainage of malignant pleural effusion, lung abscess, and pneumothorax. PMID- 7863876 TI - Scuba diving accident with near drowning and decompression sickness. PMID- 7863877 TI - Carcinoma of the lung in HIV-positive patients: findings on chest radiographs and CT scans. AB - OBJECTIVE: Several recent clinical studies have described an association between HIV seropositivity and lung cancer. The purpose of this study was to describe the spectrum of imaging findings in HIV-positive patients who had proved carcinoma of the lung. In particular, we attempted to define the role of CT in diagnosing HIV associated lung cancer. MATERIALS AND METHODS: The study population consisted of 23 HIV-positive patients from two institutions who had lung cancer diagnosed between 1989 and 1993. All patients had both chest radiographs and CT scans. The group included 19 men and four women with a mean age of 42 years. The diagnosis of lung cancer was confirmed by bronchoscopy in eight patients, by pleural fluid aspiration or pleural biopsy in seven, by percutaneous needle biopsy of a lung lesion in three, by biopsy of an extrathoracic site in four, and by thoracotomy in one. Two thoracic radiologists retrospectively evaluated the chest radiographs and CT scans to identify parenchymal masses, lymphadenopathy, pleural disease, chest wall or mediastinal invasion, and metastatic lesions. RESULTS: Fifteen (65%) of the 23 patients had a central or peripheral mass or nodule. Eight (35%) had extensive pleural disease, either as an isolated finding or in combination with other abnormalities. CT scans showed the malignant lesion underlying the extensive pleural disease in all but one case. All patients with extensive pleural disease had adenocarcinoma. No patient in the study was considered a candidate for resection on the basis of clinical and radiologic evaluation. CONCLUSION: Lung cancer in HIV-positive patients manifested most often on chest radiographs as a central or peripheral mass or nodule. Extensive pleural disease in the absence of an apparent primary lesion was the second most common major manifestation. Lung cancer therefore merits serious consideration in the differential diagnosis of extensive pleural disease in HIV-positive patients. CT was most useful in evaluating malignant lesions associated with extensive pleural disease. PMID- 7863878 TI - CT findings of atrophy of chest wall muscle after thoracotomy: relationship between muscles involved and type of surgery. AB - OBJECTIVE: Postthoracotomy atrophy of chest wall muscles results from nerve injury during surgery. After encountering patients with different patterns of chest wall muscular atrophy postthoracotomy, we performed this study to determine the relationship between type of thoracotomy and atrophic muscles as seen on CT scans. MATERIALS AND METHODS: CT scans of 58 patients who had previously undergone unilateral thoracotomy were reviewed. Forty patients had a posterolateral thoracotomy, and 18 had an anterolateral thoracotomy. In two cases, the incision extended posteriorly. Atrophy seen on CT scans was defined as a marked decrease in size or thickness of a muscle compared with the muscle on the other side. RESULTS: Atrophy of the latissimus dorsi muscle and of the inferior portion of the serratus anterior muscle was detected on CT scans in 40 patients. No atrophy was found in 16 patients. The remaining two displayed atrophy only in the serratus anterior muscle. Atrophy of the latissimus dorsi muscle and of the inferior portion of the serratus anterior muscle developed in all patients who had a posterolateral thoracotomy. Atrophy developed in only two of the 18 patients who had an anterolateral thoracotomy, and in these two, the incision had been extended posteriorly. CONCLUSION: A direct correlation was found between type of thoracotomy and site of atrophy of the chest wall muscles seen on CT scans. This finding may account for different CT appearances of the thoracic wall in patients who have had thoracic surgery. PMID- 7863879 TI - CT of the chest: minimal tube current required for good image quality with the least radiation dose. AB - OBJECTIVE: We wanted to determine minimal tube current (mAs) required for consistently good image quality on conventional 10-mm collimation chest CT and effect of tube current reduction on detection of mediastinal and lung abnormalities. Tube current reduction is desirable to reduce patient radiation dose. SUBJECTS AND METHODS: Prospectively, 30 consecutive patients (mean weight, 68 kg; range, 34-93 kg) older than 45 undergoing conventional chest CT with standard technique (120 kVp, 400 mAs) had four additional sections imaged at reduced tube current (200, 140, 80, 20 mAs) at two levels (tracheal carina and left atrium). CT scans were evaluated in random order by two independent observers who were blinded to technical factors used. Subjective image quality was graded on a five-point scale from non-diagnostic to excellent. Visualization of mediastinal adenopathy (n = 18), pleural plaques (n = 17), effusions (n = 28), lung parenchymal nodules (n = 37), and emphysema (n = 15) were assessed. The 400 mAs scan was considered the reference standard. RESULTS: When compared with the reference technique (400 mAs), the first and second (200 mAs and 140 mAs) reduction levels showed no significant difference (p > .05) in subjective image quality. A significant difference (p < .001) was seen at the third and fourth (80 mAs and 20 mAs) reduction levels. However, no significant difference (p > .05) was seen in detection of mediastinal or lung parenchymal abnormalities with different tube currents. CONCLUSION: A twofold reduction in tube current (400-140 mAs) and resultant radiation dose did not cause a significant change in subjective image quality or in detection of mediastinal or lung abnormalities with conventional chest CT. One hundred forty milliampere-seconds is the minimal tube current required to provide good image quality in patients of average weight. PMID- 7863880 TI - Non-Hodgkin's lymphoma of the breast causing miliary densities on mammography. PMID- 7863881 TI - Imaging in the preoperative evaluation of adult liver-transplant candidates: goals, merits of various procedures, and recommendations. AB - Advances in organ procurement and surgical techniques have made orthotopic liver transplantation (OLT) an accepted treatment for many adult patients with end stage hepatic disease. At present, OLT is being performed in patients with a variety of diseases, and 5-year survival is estimated at 65-78% [1]. Over 80% of hepatic transplants are performed in patients with cirrhosis or primary cholestatic liver disease, and only 5% of transplants are performed for malignant hepatic neoplasms (Table 1) [2]. Because the supply of donor organs is limited, preoperative clinical and radiologic evaluation of the transplant candidate is critical for appropriate patient selection. The main objective of preoperative imaging is to provide the surgeon with the pertinent information needed to plan and perform OLT and to exclude patients for whom surgery either is not feasible or will be of no benefit. PMID- 7863882 TI - Conspicuity of hepatic metastases on helical CT: effect of different time delays between contrast administration and scanning. AB - OBJECTIVE: The purpose of this study was to compare two time delays between injection of contrast material and helical CT scanning to determine relative conspicuity of hepatic metastases. SUBJECTS AND METHODS: Twenty-five patients with hepatic metastases were examined with helical CT. The first imaging phase was initiated at 50 sec and the second 75 sec after the start of contrast material injection (3 ml/sec, 150 ml). Differences in lesion and liver attenuation were measured quantitatively. Four radiologists used a 5-point scale to assess lesion conspicuity subjectively. RESULTS: Mean differences in enhancement between liver and lesion were 41 H during the first phase and 59 H for the second phase (p = .0001). Radiologists' conspicuity score averaged 2.4 for lesions in the first phase versus 3.3 for lesions in the second phase (p = .0001). In 56 (88%) of 64 lesions, objective measurements showed greater enhancement of lesions during the later phase. Radiologists found 60 (94%) of 64 lesions to be more conspicuous on these later images. CONCLUSION: Our results show that conspicuity of hepatic metastases on helical CT scans is better with a 75-sec scan delay between contrast administration and scanning than with a 50-sec scan delay. The longer delay time should be used when scanning is used to detect metastases. PMID- 7863883 TI - Distinction between cavernous hemangiomas of the liver and hepatic metastases on CT: value of contrast enhancement patterns. AB - OBJECTIVE: Differentiating between cavernous hemangiomas of the liver and hepatic metastases on the basis of single-pass, contrast-enhanced CT is a significant and frequently encountered diagnostic challenge. Recognition of characteristic enhancement features of cavernous hemangiomas can aid in effectively distinguishing between these lesions. The purpose of this study was to determine sensitivity and specificity of dense, globular enhancement for differentiating cavernos hemangiomas and metastases during single-pass, contrast-enhanced CT. MATERIALS AND METHODS: CT appearance of 133 lesions in 91 patients with cavernous hemangiomas (44 patients) or metastases (47 patients) was retrospectively evaluated in a blinded review. CT examinations were performed with nonhelical technique following injection of 150 ml of contrast material. All patients with metastases had pathologic proof (n = 47). Patients with cavernous hemangiomas were clinically stable for at least 2 years after CT (n = 43) or had tissue proof (n = 1). All lesions were evaluated based on the following criteria: (1) Type of enhancement: globular, linear, diffuse and homogeneous, or diffuse and heterogeneous. (Globular enhancement was considered to be present when enhancing nodules less than 1 cm in diameter were seen within lesions.) (2) Continuity of enhancing tissue: continuous or noncontinuous. (Uninterrupted collections of contrast material within at least 50% of a lesion were considered continuous. Multiple, separate collections of contrast material were considered noncontinuous.) (3) Degree of enhancement: hypo-, iso-, or hyperdense relative to the aorta. (4) Distribution of enhancement: peripheral, central, or mixed. RESULTS: Seventy-six percent of cavernous hemangiomas had globular enhancement, compared to 10% of metastases (p < .001). Seventy-two percent of cavernous hemangiomas had enhancement isodense with the aorta, and 96% of metastases were hypodense (p < .001). Sixty-seven percent of cavernous hemangiomas had peripheral enhancement, compared to 38% of metastases (p < .001). The combined finding of globular, isodense enhancement was seen in 67% of cavernous hemangiomas and none of the metastases. Only 10% of cavernous hemangiomas had nonglobular, hypodense enhancement, compared with 90% of metastases. Combining all criteria, reviewers correctly classified 122 (92%) of the lesions. Presence of globular enhancement, isodense with the aorta, was 67% sensitive and 100% specific in differentiating cavernous hemangiomas from hepatic metastases. CONCLUSION: In most cases, differentiation of cavernous hemangiomas from hepatic metastases can confidently be made with single-pass, contrast-enhanced CT. Globular enhancement, isodense with the aorta, is 67% sensitive and 100% specific in differentiating cavernous hemangiomas and hepatic metastases. PMID- 7863884 TI - Splenic involvement in pancreatitis: spectrum of CT findings. AB - The pancreas is located deep within the retroperitoneum in the anterior pararenal space. The distal portion of the pancreatic tail extends along the course of the splenic artery and vein (Fig. 1) and enters the splenic hilum contained within the splenorenal ligament. Because of these anatomic relationships, the spleen and splenic vessels may be involved by pancreatitis. Although rare (frequency, 1-5%), splenic involvement by pancreatitis includes intrasplenic pseudocyst, abscess, hemorrhage, infarction, splenic rupture, and vascular injury. Because these complications can be life-threatening, the extent and course of the disease are closely monitored with CT to determine whether and when aggressive intervention is necessary to avoid catastrophic clinical outcomes. The purpose of this essay is to illustrate the spectrum of CT findings in cases of pancreatitis with splenic involvement. PMID- 7863885 TI - MR imaging of adrenal masses: value of chemical-shift imaging for distinguishing adenomas from other tumors. AB - OBJECTIVE: CT and conventional MR imaging are helpful in characterizing adrenal tumors, but a specific diagnosis is not achieved for a substantial number of lesions. Chemical-shift imaging relies on the different resonance frequencies of protons in water and triglyceride molecules and therefore may permit a more specific diagnosis of adrenal adenomas, which are known to contain abundant lipid. The purpose of this study was to evaluate the usefulness of chemical-shift MR imaging in the differentiation of adrenal adenomas from other adrenal masses. SUBJECTS AND METHODS: Forty-one adrenal masses (17 nonhyperfunctioning adenomas, two aldosteronomas, six pheochromocytomas, one ganglioneuroma, five adrenal carcinomas, one lymphoma, seven metastases, one case of extramedullary hematopoiesis, and one leiomyosarcoma) suspected clinically or identified by sonography or CT in 38 patients were prospectively evaluated with MR imaging. Pathologic proof of diagnosis was obtained for 28 lesions, and stability on imaging follow-up (mean, 19 months) was accepted as proof of diagnosis of benign adenoma for 13 lesions. In-phase T1-weighted spin-echo sequences (500/20 [TR/TE]) and opposed-phase gradient-echo sequences (142/6.3, flip angle = 90 degrees) of the adrenal regions were applied. Quantitative analysis of signal intensity loss in the adrenal lesions relative to reference tissues (liver, muscle, and spleen) on in-phase and opposed-phase sequences was done to differentiate adenomas from nonadenomas. Region-of-interest signal intensity measurements were obtained in a standard fashion by selection of the largest possible representative sample. RESULTS: Using liver as the reference standard, we found that mean signal intensity ratios were 0.47 (range, 0.23-0.97) for adrenal adenomas and 0.88 (range, 0.65-1.32) for nonadenomas; signal intensity ratios for two adenomas overlapped those of the nonadenomas. Using muscle as the reference standard, we found that mean signal intensity ratios were 0.44 (range, 0.22-0.66) for adrenal adenomas and 0.85 (range, 0.59-1.39) for nonadenomas; signal intensity ratios for two adenomas overlapped those of the nonadenomas. Using spleen as the reference standard, we found that mean signal intensity ratios were 0.45 (range, 0.27-0.73) for adrenal adenomas and 0.97 (range, 0.8-1.18) for nonadenomas, with no overlap. The mean signal intensity ratios were significantly different between adenomas and nonadenomas for all three reference tissues (p < .001). CONCLUSION: Our results show that chemical-shift MR imaging is an important new technique that enables the differentiation of adrenal adenomas from other adrenal masses, reducing the need for biopsy and prolonged imaging follow-up in patients with adrenal tumors. PMID- 7863886 TI - Characterization of adrenal masses. PMID- 7863887 TI - Lymphoma and leukemia involving the testicles: findings on gray-scale and color Doppler sonography. AB - OBJECTIVE: The purpose of this study was to determine the gray-scale and color Doppler sonographic appearance of testicular lymphoma and leukemia to aid in its differentiation from primary testicular neoplasms and inflammatory processes. MATERIALS AND METHODS: We retrospectively reviewed the testicular sonograms of eight male patients 5-74 years old (mean age, 43 years) with pathologically proved testicular leukemia or lymphoma. All patients presented with testicular enlargement. Gray-scale sonograms were obtained to determine the presence or absence of a mass, focal nodule, or diffuse infiltration, as well as the degree of parenchymal echogenicity. Color Doppler sonography was applied in each case to determine the degree of vascularity compared with normal ipsilateral or contralateral testicular parenchyma. In patients with focal, measurable lesions, the size was correlated with its color Doppler sonographic appearance. RESULTS: Gray-scale sonograms showed either homogeneously hypoechoic testes in patients with diffuse round-cell infiltration or multifocal hypoechoic lesions of various sizes. Five patients had a total of 11 focal lesions that ranged in size from 8 mm to 26 mm in maximum diameter (mean diameter, 16 mm). Color Doppler sonography revealed increased intralesional flow in all areas of lymphomatous or leukemic involvement irrespective of lesion size. CONCLUSION: Our results show that testicular lymphoma and leukemia are hypervascular on color Doppler sonograms regardless of the size of the tumor. Although color Doppler sonography may provide useful information, differentiating round-cell infiltration from inflammatory processes of the testes remains difficult. PMID- 7863888 TI - The aberrantly fed varicocele: frequency, venographic appearance, and results of transcatheter embolization. AB - OBJECTIVE: Retrograde flow in the internal spermatic vein, which is characteristic of varicocele, can occur despite competent valves because of the presence of bypassing anastomoses. The resulting condition has been called aberrantly fed varicocele. The purpose of this study was to determine the frequency of aberrantly fed varicocele, to analyze its various venographic appearances, and to review the results of attempted embolotherapy. SUBJECTS AND METHODS: We performed left-sided (n = 213) and/or right-sided (n = 121) spermatic venography in 213 patients who were examined for infertility (n = 179), for physical complaints of their varicocele (n = 17), or for varicocele impeding testicular growth (n = 17). The resulting 334 venograms were subdivided as negative or positive for varicocele, and positive venograms were further classified as showing normally or aberrantly fed varicoceles. The aberrantly fed varicoceles were classified according to the sites of the bypassed competent valves and the levels at which the bypassing anastomoses joined the internal spermatic veins. The technical success rate of 192 attempted embolizations of normally and aberrantly fed varicoceles was determined. RESULTS: Of the left sided spermatic venograms, 42 (20%) were negative and 171 (80%) were positive for varicoceles, which in turn consisted of 125 normally and 30 (19%) aberrantly fed varicoceles (16 could not be classified). On the right side, 78 (64%) venograms were negative and 43 (36%) were positive for varicoceles, consisting of 34 normally and seven (17%) aberrantly fed varicoceles (two were not classified). Venographic classification showed that about half of the cases were in patients with competent orificial valves, which were bypassed by anastomoses joining the internal spermatic veins in their cranial lumbar subsegments. Competent valves lower down were seen only on the left side, and anastomoses joining the internal spermatic veins in their cranial pelvic subsegments occurred relatively more frequently on the right side. Coil embolization was attempted in 118 left-sided and 32 right-sided normally fed varicoceles and in 30 left-sided and seven right sided aberrantly fed varicoceles. The technical success rate was 97% for left- and right-sided normally fed varicoceles and 73% for left-sided and 57% for right sided aberrantly fed varicoceles. CONCLUSION: Aberrantly fed varicoceles are found in 17-19% of patients examined with spermatic venography. Coil embolization of aberrantly fed varicoceles is usually successful, but not as reliably as with normally fed varicoceles. PMID- 7863889 TI - Tuberculosis of the spine: imaging features. AB - Spinal tuberculosis, the most common form of skeletal involvement, is increasing in prevalence because of the resurgence of tuberculosis during the past decade in patients with AIDS, the spread of tuberculosis among the homeless, and the expanding immigrant population. Spinal infection is usually the result of hematogenous seeding of the vertebral body, and the diagnosis often remains elusive because of the indolent nature of tuberculous infection. As a result, the radiographic findings and the signs and symptoms are typically far advanced when the diagnosis is finally established. Radiographic manifestations of tuberculous spondylitis include intraosseous and paraspinal abscess formation, subligamentous spread of infection, vertebral body destruction and collapse, and extension into the spinal epidural space. Significant instability and deformity of the spine can result, mandating prompt diagnosis and treatment to prevent permanent neurologic damage. The purpose of this essay is to illustrate the broad spectrum of imaging findings on plain radiographs, bone scans, CT scans, myelograms, and MR images of patients with spinal tuberculosis. The value of MR imaging in determining the extent of disease is demonstrated. PMID- 7863890 TI - Lumbar spine after surgery for herniated disk: imaging findings in the early postoperative period. AB - Imaging the lumbar spine after surgery for disk herniation is all too often an unrewarding challenge. A constellation of findings is inevitable, and determining their significance is often impossible. The challenge is greatest during the first few months following surgery, when the rules of scar enhancement, deformity, and mass effect do not apply to differentiation of the abnormal from the normal. A clear understanding of normal postoperative healing is necessary to avoid overreaction to misleading findings. This report reviews imaging of the lumbar spine in the early postoperative period (i.e., the first 6 months after surgery), focusing on the normal healing process that so often mimics complicating or recurrent disease. PMID- 7863891 TI - Multiple sclerosis. PMID- 7863892 TI - Dissection of the carotid and vertebral arteries: imaging with MR angiography. AB - Arterial dissection occurs when an intimal tear allows blood to enter the arterial wall, potentially compromising the lumen and reducing blood flow. Carotid and vertebral artery dissections typically occur after major trauma, although they also can arise spontaneously or after trivial injury. Arterial dissection has been associated with a variety of factors, including hypertension, fibromuscular dysplasia, Marfan syndrome, cystic medial necrosis, oral contraceptives, drug abuse (sympathomimetics), and infection [1-8]. It is important to recognize arterial dissection early so that prompt treatment can be initiated to prevent ischemic complications [1]. In this essay, we illustrate the use of MR angiography in the diagnosis of carotid and vertebral artery dissection. PMID- 7863893 TI - Fibrous dysplasia of the temporal bone: imaging findings. AB - Lichtenstein [1] in 1938 coined the term fibrous dysplasia to describe a disorder characterized by the progressive replacement of normal bone elements by fibrous tissue. Histopathologically, these lesions consist of an abnormal proliferation of fibrous elements intermixed with haphazardly arranged trabeculae of woven bone. The disease can involve any bone in the body. In the head and neck, the skull and facial bones are involved in 10-25% of cases of monostotic fibrous dysplasia and in 50% of the polyostotic variety. Involvement of the temporal bone, however, is relatively rare, and only 53 cases have been reported. The three major radiographic classifications of fibrous dysplasia are pagetoid, sclerotic, and cystic. Any of these types may involve the temporal bone and related structures, including the external canal, middle ear, jugular foramen, or, rarely, the otic capsule. In this essay, we illustrate the radiographic features of the disease based on our experience with seven cases, seen at our institution since 1977, of fibrous dysplasia involving the temporal bone. PMID- 7863894 TI - Hemangiomas in the calvaria: imaging findings. AB - Lesions of the skull vault are fairly common; however, they are often difficult to diagnose. By using specific imaging criteria, one may readily diagnose a calvarial hemangioma. These lesions account for 10% of benign primary neoplasms of the skull [1]. This essay illustrates the spectrum of imaging findings seen on plain radiography, CT, MR imaging, and angiography for patients with calvarial hemangiomas. PMID- 7863895 TI - Variable bandwidth steady-state free-precession MR imaging: a technique for improving characterization of epidermoid tumor and arachnoid cyst. PMID- 7863896 TI - Obstructive lung disease in children after allogeneic bone marrow transplantation: evaluation with high-resolution CT. AB - OBJECTIVE: Obstructive lung disease is a major complication of bone marrow transplantation related to graft-versus-host disease. The purpose of this study was to determine the usefulness of high-resolution CT to evaluate obstructive lung disease occurring in children after bone marrow transplantation. MATERIALS AND METHODS: Ten high-resolution CT scans of the lungs were obtained in seven children who developed chronic obstructive lung disease after bone marrow transplantation. All seven patients had chronic graft-versus-host disease. Spirometry, the gold standard test, confirmed airflow obstruction in each case, five prior to high-resolution CT. Two patients were too young to have spirometry until 10 and 15 months respectively after successful high-resolution CT. Selected images from these studies were randomized with similar images from five control subjects and reviewed blindly. All images from scans in patients with obstructive lung disease were analyzed retrospectively for parenchymal hypoattenuation, bronchial dilatation, bronchial wall thickening, and abnormal parenchymal opacity. Expiratory air-trapping was assessed on cine high-resolution CT done in four cases. RESULTS: Three blinded observers each correctly identified all five controls among 15 high-resolution CT examinations. No scan from a patient with obstructive lung disease was considered normal. Areas of parenchymal hypoattenuation affected 35 of 35 lobes of the lung. Expiratory air-trapping was shown by cine high-resolution CT. Subsegmental or segmental bronchial dilatation was seen in 23 of 25 lobes in five patients. Bronchial wall thickening was not a prominent feature. Increasing abnormality was demonstrated in three patients on follow-up high-resolution CT. The high-resolution CT abnormalities were similar to those reported in patients with bronchiolitis obliterans. CONCLUSION: High resolution CT of the lungs can show extensive abnormality in children who develop chronic obstructive lung disease after bone marrow transplantation. High resolution CT is a useful noninvasive technique in the evaluation of this disease. PMID- 7863897 TI - Rhabdoid tumors of the kidney in children: CT findings. AB - OBJECTIVE: The purpose of this study was to identify CT characteristics of rhabdoid tumor of the kidney, a rare, aggressive, malignant neoplasm of unknown origin that occurs mainly in infants and young children. MATERIALS AND METHODS: CT scans of eight children (newborn to 13 years old; mode, 4 months old; six boys and two girls) with histopathologic diagnosis of rhabdoid tumor of the kidney were evaluated retrospectively by two of the authors, who were not blinded to the diagnosis. All eight CT scans were performed with intravenous and oral contrast, and noncontrast intravenous CT scans were available in four cases. The following CT characteristics were evaluated: location of tumor within the kidney; presence of calcification, subcapsular hematoma, multiple tumor lobules, enlarged vessels, vascular invasion, or central tumor necrosis or hemorrhage; visibility of tumor margin; distant metastasis; and primary tumor size. RESULTS: All eight primary tumors (five on the left, one of which had contralateral renal nodules) were central in location and involved the hilum. Calcification outlining the tumor lobule was present in two of the four tumors on noncontrast CT scans. Subcapsular hematoma was seen in five children. Tumor necrosis and hemorrhage were seen in seven children. Tumors were well defined from the renal cortex in four children. Lobules of tumor were seen in seven children. CONCLUSION: CT findings of calcification, subcapsular hematoma, and lobular appearance in a large, centrally located, and heterogeneous renal mass in a child suggest a rhabdoid tumor of the kidney. PMID- 7863898 TI - Complete duplication of the ureter with ureteropelvic junction obstruction of the lower pole of the kidney: imaging findings. AB - OBJECTIVE: The purpose of our study was to identify the radiographic signs that aid in the diagnosis of obstruction of the ureteropelvic junction of the lower pole (or moiety) of the kidney in children with complete duplication of the ureter and to describe the imaging appearance of this unusual cause of lower-pole hydronephrosis. MATERIALS AND METHODS: We reviewed the medical records and imaging studies of 16 children (11 boys and five girls) with complete ureteral duplication and ureteropelvic junction obstruction of the lower pole of the kidney over a 5-year period. standard criteria for determining urinary tract obstruction were used. RESULTS: Sonograms showed a lower-pole abnormality (hydronephrosis or cystic mass) in all 15 children who underwent sonography. Voiding cystourethrography, performed for all children, showed vesicoureteral reflux into the lower pole in addition to ureteropelvic junction obstruction in eight children (seven boys and one girl). For the other eight, the diagnosis of lower-pole ureteropelvic junction obstruction was made by excretory urography, at times complemented with diuretic renography or retrograde ureterography. CONCLUSION: Ureteropelvic junction obstruction of the lower pole of the kidney in children with complete duplication of the ureter should be a diagnostic consideration when there is dilatation of the lower moiety. Imaging changes parallel those of ureteropelvic junction obstruction in a nonduplicated system. This anomaly, unlike others seen in duplication, appears to be more common in boys than in girls. PMID- 7863899 TI - Anomalous midline location of the descending aorta: a cause of compression of the carina and left mainstem bronchus in infants. PMID- 7863900 TI - Sonographic evaluation of intrauterine growth retardation. AB - Intrauterine growth retardation (IUGR) may arise from a variety of causes, including placental insufficiency, maternal diseases, and fetal anomalies. Sonography plays a number of important roles in the diagnosis and management of growth retardation. Diagnosis of IUGR is based on fetal measurements, assessment of amniotic fluid volume, and other sonographic findings. Once IUGR has been diagnosed, sonography can help establish its cause. If a lethal cause is excluded, the fetus is monitored for the remainder of the pregnancy using sonography, including serial fetal measurements, biophysical profiles, and Doppler waveform indexes. Used appropriately, sonography can improve the outcome of fetuses with IUGR. PMID- 7863901 TI - Detection of obstructive uropathy in the fetus: predictive value of sonographic measurements of renal pelvic diameter at various gestational ages. AB - OBJECTIVE: The goal of our study was to analyze the fetal renal pelvic diameters measured sonographically at several gestational intervals in live-born neonates subsequently found to have either obstructive uropathy or normal kidneys. This information will improve the efficacy of sonography in the diagnosis of obstructive uropathy. SUBJECTS AND METHODS: From an ongoing prospective study assessing the significance of fetal renal pelvic diameters of 4 mm or more at obstetric sonography, the findings in 29 obstructed kidneys in 24 babies were compared with the findings in 380 kidneys from 233 infants who had no obstruction. Twenty-three infants had unilateral obstruction of the ureteropelvic junction, two had unilateral renal obstruction at the ureterovesical junction, one had posterior urethral valves and in addition had both kidneys obstructed because of obstruction at the ureterovesical junction, one kidney was obstructed because of megaloureter, and one kidney was obstructed because of obstruction in a duplex collecting system. Obstruction was identified on nephrostograms, excretory urograms, or radionuclide renograms. The sonographic findings were compared at three gestational age ranges: 16-23 weeks' gestation, 24-30 weeks' gestation, and 31-40 weeks' gestation. The progression of pelvic dilatation in both groups (12 obstructed and 86 unobstructed) was analyzed for the subset of kidneys examined in all three time periods. RESULTS: At 16-23 weeks' gestation, the difference in mean pelvic diameter between obstructed and unobstructed kidneys was not statistically significant, but the difference between obstructed and unobstructed groups at 24-30 weeks' and 31-40 weeks' gestation was significant (p < .001). Renal pelvic diameter showed a much greater rise in diameter through pregnancy in the obstructed group than in the unobstructed group (p < .0003). The sensitivity of the cutoff point of 4-mm renal pelvic diameter for detecting obstruction was 76% before 23 weeks' gestation, including kidneys with a marked decrease in function postnatally; the sensitivity of a 10-mm cutoff point at 16-23 weeks' gestation was 12%. The likelihood that a fetus had renal obstruction increased with increasing diameter of the fetal renal pelvis in all three time periods. CONCLUSION: Kidneys with significant obstruction postnatally may have no dilatation of the renal pelvis before 23 weeks' gestation. Most obstructed kidneys had pelvic diameters of less than 10 mm before 23 weeks' gestation. During pregnancy, renal pelvic diameter increases at a greater rate in kidneys that later are shown to be obstructed than in those that are not obstructed. PMID- 7863902 TI - Fetal aqueductal stenosis diagnosed sonographically: how grave is the prognosis? AB - OBJECTIVE: Aqueductal stenosis is a common cause of fetal hydrocephalus. Published studies of neonates with aqueductal stenosis have noted variable outcomes, with normal development seen in 24-86% of cases. In an attempt to better assess long-term outcomes in cases diagnosed in utero and to determine what prenatal sonographic findings might be used to predict prognosis, a retrospective analysis of patients with aqueductal stenosis was done. MATERIALS AND METHODS: Fifty-three consecutive cases of aqueductal stenosis discovered in utero at two high-risk obstetrical centers in Seattle between 1980 and 1993 were studied. Parents elected to continue pregnancy in 39 of these cases. Two months to 10 years of long-term follow-up was available in 30 patients, who form our study group. Prenatal sonograms, postnatal cranial ultrasound, and head CT and MR were evaluated. Prenatal sonographic data collected included the biparietal diameter, size of the lateral and third ventricles, the ratio of the two, and thickness of the frontoparietal cortical mantle. Medical records provided an assessment of development based on physical examination, meeting of major milestones, and neuropsychological testing. The in utero diagnosis of aqueductal stenosis was confirmed by postnatal CT, MR imaging, sonography, or autopsy. RESULTS: Within the study group of 30 patients, eight died in the postnatal period and four died subsequently. Of the 22 patients with adequate postnatal follow-up, moderate or severe developmental delay was present in 16 (73%). Normal developmental milestones were met in only three (10%) of all 30 patients and in 14% of those surviving the neonatal period. Although size of the lateral and third ventricles was not a useful predictor of long-term prognosis, the ratio of the two, as well as thickness of the frontoparietal cortical mantle, was weakly associated with long-term prognosis. No correlation was found between biparietal diameter and outcome. CONCLUSION: As compared with previous reports, prenatal diagnosis of aqueductal stenosis carries a grave prognosis. Twelve of the 30 patients died, for an overall mortality of 40%. Normal development was seen in only 10%, significantly less than in prior studies. PMID- 7863903 TI - The atria of the fetal lateral ventricles: a sonographic study of normal atrial size and choroid plexus volume. AB - OBJECTIVE: Evaluation of the cerebral ventricular system is a routine part of all fetal sonographic examinations. Ventriculomegaly and decreased choroid volume are indicators of poor fetal outcome, so it is important to know the normal variation of these parameters. The present study describes the normal size of the fetal lateral ventricular atrium and the normal amount of choroid plexus within the atrium during the second and third trimesters. SUBJECTS AND METHODS: Six hundred eight consecutive, healthy, singleton fetuses from 13 to 42 weeks' menstrual age were examined prospectively. The atrium of the lateral ventricle was measured in the axial and coronal planes. For each axial measurement, the width of the choroid plexus was determined. RESULTS: An axial atrial measurement was obtained in 88% of the fetuses, and a coronal atrial measurement was obtained in 84%. The mean measurement and one standard deviation are 6.5 +/- 1.5 mm in the axial plane and 6.6 +/- 1.5 mm in the coronal plane. Ninety-eight percent of all measured atria were at least 60% filled by choroid plexus, and in all cases the atria were at least 50% filled. Complete filling by choroid plexus occurred in 58% of cases. CONCLUSION: This large prospective study confirms previous observations of mean atrial size. However, four standard deviations above the mean is 12 mm, suggesting currently used cutoffs for normal atrial size are too low. Other parameters, such as choroid plexus filling, may be helpful markers of normalcy in fetuses with atrial measurements between 8 and 12 mm. PMID- 7863904 TI - Carbon dioxide digital subtraction angiography: expanding applications and technical evolution. AB - Although several noninvasive techniques now exist for vascular imaging, including MR imaging, three-dimensional CT, and color-flow and duplex sonography, the gold standard to which these techniques are compared remains catheter angiography. Cut film and digital subtraction angiography (DSA) using iodinated contrast material are the standard methods by which vascular imaging is performed. However, despite the development of low-osmolar contrast agents, premedication regimens, and careful patient selection, adverse reactions to contrast material, including idiosyncratic reactions and contrast-induced nephropathy, continue to occur in a small number of patients [1-3]. Carbon dioxide (CO2) was developed as an alternative to iodinated contrast material to avoid these problems [4]. Once the behavior of intravascular gas, the methods of safe delivery, and the principles of successful imaging are understood, the use of CO2 as an intravascular contrast agent during DSA allows accurate imaging with little risk. Recent advances in delivery systems, postprocessing capabilities, and its extension to new vascular interventional procedures have greatly expanded the usefulness of CO2 angiography in both diagnostic and interventional vascular radiology. PMID- 7863905 TI - Fatal reaction to gadopentetate dimeglumine. PMID- 7863906 TI - Use of data in a radiology information system for labeling computed radiographs: an interface to connect the two systems. AB - Computers have greatly facilitated the processing and storage of radiologic information. Manufacturers of radiology information systems (RISs) are gradually incorporating options for interfacing their products with other computers (e.g., hospital information systems). However, a growing need exists to also interface RISs with digital radiologic equipment so that images (e.g., computed radiographs of the chest and skeleton) are automatically labeled with identification data. Such connectivity would eliminate redundant work by technologists, decrease errors in the labeling of images, and increase the consistency of patients' data within a radiology department. Unfortunately, the rapid advances in digital technology, combined with the lack of a well-defined standard for the transfer of demographic information between dissimilar systems, have delayed development of these interfaces. We have developed a widely applicable method to automatically transfer patients' demographic data from an RIS to a commercially available computed radiography system. A personal computer is configured with inexpensive programmable telecommunications software to create an interactive gateway, which eliminates the need for redundant data entry (compared with entering data once on the RIS and again on the stand-alone computed radiography system), and thus also decreases errors in the labeling of images. PMID- 7863907 TI - American martyrs to radiology. Louis Andrew Weigel (1854-1906). 1936. PMID- 7863908 TI - A history of the Department of Radiology at Stanford University. PMID- 7863909 TI - How common are incomplete pulmonary fissures, and what is their clinical significance? PMID- 7863910 TI - Performing high-resolution computed tomography in asbestos-exposed patients. PMID- 7863911 TI - Should patients who undergo CT scanning of the abdomen for blunt trauma always have a CT scan of the pelvis as well, regardless of the severity and location of the trauma? PMID- 7863912 TI - What is the role of barium enema in the patient with suspected appendicitis? PMID- 7863913 TI - What pulse sequences should be used when the clinical question is "rule out superior sagittal sinus thrombosis"? PMID- 7863914 TI - Breast tissue expander: MR imaging artifact. PMID- 7863915 TI - Mammographic appearance of calcinosis in dermatomyositis. PMID- 7863916 TI - CT of bowel obstruction: interpretation using cine-paging. PMID- 7863917 TI - Biliary ascariasis: sonographic findings. PMID- 7863918 TI - Hepatic fascioliasis: CT findings. PMID- 7863919 TI - CT arterial portography for detecting recurrent hepatic metastases. PMID- 7863920 TI - Alkaline-encrusted cystitis: imaging findings. PMID- 7863921 TI - Sonography in optic disk drusen. PMID- 7863922 TI - Subdural hematoma overlooked on a CT scan of the paranasal sinuses. PMID- 7863923 TI - Thrombus deformation of inferior vena caval filter. PMID- 7863924 TI - Anodyne imagery as an alternative to i.v. sedation. PMID- 7863925 TI - Guided imagery techniques. PMID- 7863926 TI - Radiation exposure in endovascular surgery of the head and neck. AB - PURPOSE: To evaluate the radiation risk to the operator and the patient during endovascular surgery of the head and neck. METHODS: The dose was measured using thermoluminescence dosimeters attached at the body surface of the operator and the patient during 15 endovascular surgeries (3 for arteriovenous malformation, 8 for dural arteriovenous fistulas, and 4 for other disorders of the head and neck). The dose was measured at seven sites on the operator and at five sites on the patient. RESULTS: The mean number of digital subtraction angiography studies and fluoroscopy time were 21 +/- 10 and 73 +/- 24 minutes, respectively. The equivalent dose range at each site in the operator was 0.12 to 0.88 mSv (glabella), 0.06 to 1.1 and 0 to 0.09 mSv (neck, outside and inside the protector, respectively), 0 to 0.20 mSv (left should, inside the protector), 0.09 to 1.99 mSv (left arm), 0.05 to 3.55 mSv (left hand), and 0 to 0.49 mSv (pubis, inside the protector). Those in the patients were 3.1 to 136 mSv (glabella), 13 to 5441 mSv (right temporal area), 4 to 186 mSv (left temporal area), 0.1 to 51 mSv (neck), and 0 to 0.62 mSv (pubis). CONCLUSIONS: The total doses at the operator's eyes and left hand during the course of a year may exceed the dose limits recommended by the International Commission on Radiological Protection. Operators should wear not only body protectors, but also thyroid protectors and lead glass spectacles. The equivalent dose at the right temporal area of the patient may exceed the deterministic dose for transient erythema or alopecia of the skin even in one endovascular procedure. PMID- 7863927 TI - Radiation doses to patients in neurointerventional procedures. AB - PURPOSE: To evaluate stochastic and deterministic risks associated with neurointerventional procedures for the patient. METHODS: Eight neurovascular interventional procedures were evaluated to determine the entrance skin dose and effective dose for the patient. Dosimetry was done with thermoluminescence dosimeters. The highest dose on the patient's head was recorded as the maximum entrance skin dose. The equivalent dose was obtained by conversion of the dose area product using published conversion tables. RESULTS: The maximum entrance skin dose varied from 129 to 1335 mGy. The mean effective dose was 1.67 mSv with a range of 0.44 to 3.44 mSv. No deterministic effect has been encountered. Stochastic risk linked to the highest effective dose value was approximately one death by fatal cancer for every 6000 procedures, according to the new International Commission on Radiological Protection coefficient. CONCLUSIONS: Because no deterministic effect has been detected, and stochastic risks were very low, radiation hazard to the patient is a minor consideration in deciding whether to undertake a neurointerventional procedure. PMID- 7863928 TI - Hazards evaluation of neuroangiographic procedures. PMID- 7863929 TI - Safety and efficacy of delayed intraarterial urokinase therapy with mechanical clot disruption for thromboembolic stroke. AB - PURPOSE: To evaluate safety and efficacy of delayed intraarterial urokinase therapy with mechanical disruption of clot to treat thromboembolic stroke. METHODS: Thirteen patients with cerebral thrombolic disease (10 carotid territory, 3 basilar territory) were treated with catheter-directed intraarterial urokinase therapy with mechanical disruption of the clots. All patients were excluded from a 6-hour multicenter thrombolytic trial by either time, recent surgery, age, seizure, or myocardial infarction. Time elapsed before treatment ranged from 3.5 to 48 hours (12 +/- 13 hours), with 200,000 to 900,000 U of urokinase used. RESULTS: Ten patients had successful vessel recanalization, confirmed by repeat angiography. Cases with distal branch vessel occlusions were less likely to recanalize. Asymptomatic hemorrhagic conversion occurred in 2 patients on repeat scans. Both acute neurologic and functional outcomes were assessed with significant improvement occurring in 9 (69%) of 13 patients at 48 hours (greater than four-point change on the National Institutes of Health scale) and in 100% of 3-month survivors. All patients who improved had normal initial CT scans. CONCLUSIONS: Intraarterial cerebral thrombolysis with mechanical disruption of clot seems to be a useful therapy in selected stroke cases even after 6 hours. PMID- 7863930 TI - Percutaneous transluminal angioplasty adjunct to thrombolysis for acute middle cerebral artery rethrombosis. AB - PURPOSE: To report three patients, each of whom had acute rethrombosis of a reopened middle cerebral artery after urokinase treatment for proximal stenosis (percutaneous transluminal angioplasty of the stenosis was performed adjunctive to the thrombolytic treatment to preserve the success of the thrombolysis), and a fourth patient who had percutaneous transluminal angioplasty right after the completion of thrombolysis and had no rethrombosis despite a partial dilatation of the severe stenosis. METHODS: Thrombolytic treatment was carried out by a coaxial technique with a Tracker 18 catheter through a 5-F angiographic catheter; 80,000 U in 5 mL of urokinase were intermittently injected every 15 minutes after an initial dose of 250,000 U. All patients were given 3000 U of heparin with a booster dose of 1000 U every hour. Angioplasty was performed with a Stealth catheter balloon, 2 to 3 mm x 1.5 cm. RESULTS: Three patients recovered without hemorrhage after percutaneous transluminal angioplasty and thrombolytic treatment. Percutaneous transluminal angioplasty was unsuccessful in one patient because of the inability to pass a 2-mm Stealth balloon catheter, and the result was a second rethrombosis. This patient had a poor recovery. CONCLUSION: Acute thrombosis of the middle cerebral artery may be associated with severe proximal stenosis. Rethrombosis may occur even after complete thrombolysis. Percutaneous transluminal angioplasty may be safely performed to prevent rethrombosis. PMID- 7863931 TI - Physical characteristics of balloon catheter systems used in temporary cerebral artery occlusion. AB - PURPOSE: To compare and contrast the physical characteristics of balloon catheter systems used for temporary cerebrovascular occlusion. METHOD: Commonly used temporary occlusion systems were evaluated to determine: (a) balloon compliance; (b) balloon diameter versus volume; (c) balloon pressure versus volume; (d) simulated vessel wall pressure versus volume; (e) balloon failure volume; and (f) balloon deflation rate. Observations were made concerning construction differences that affect the potential safety of a balloon system or the way it is used. RESULTS: The nondetachable balloon system demonstrating the best compliance characteristics and lowest radial pressure generation was the nondetachable silicone balloon (Interventional Therapeutics Corporation, San Francisco, Calif). Diameter versus volume curves for all systems reveal an initial nonlinear expansion that could contribute to vessel overexpansion during occlusion. CONCLUSION: Balloon systems vary in construction, method of introduction, and compliance. Knowledge of these characteristics, as well as of nonlinear balloon expansion, should aid balloon selection and appropriate use while helping to minimize complications. PMID- 7863932 TI - Comparison of thallium-201 and F-18 FDG SPECT uptake in squamous cell carcinoma of the head and neck. AB - PURPOSE: To compare the uptake of 2-[F-18] fluoro-2-deoxy-D-glucose (fludeoxyglucose F-18; F-18 FDG) and thallous chloride Tl 201, using single photon emission CT (SPECT), for the detection and location of squamous cell carcinoma of the head and neck. METHODS: Five patients with biopsy-proved squamous cell carcinoma of the upper aerodigestive tract underwent both F-18 FDG and thallium-201 SPECT on the same day. F-18 FDG SPECT was performed using a dual head gamma camera equipped with commercially available, extremely high-energy collimators (full width half-maximal height, 17 mm for 511 keV photons). Tumor size was estimated at 1.0 to 5.0 cm3 in these cases. RESULTS: F-18 FDG SPECT showed five of five primary tumors. In two of the five cases, normal salivary gland activity severely limited thallium SPECT, and the tumors could not be definitively identified. Two of four lymph node groups that were positive for metastatic disease by CT criteria were shown by F-18 FDG SPECT. None were seen with thallium imaging. In one case, F-18 FDG SPECT was able to show a tumor that was not visible on CT. CONCLUSIONS: F-18 FDG has advantages over Tl-201 as a squamous cell carcinoma imaging agent (primarily because of its reduced salivary activity). F-18 FDG SPECT has potential as a viable, less expensive alternative to F-18 FDG positron emission tomography. The ultimate value of F-18 FDG SPECT imaging for detecting occult malignancy, monitoring therapeutic effectiveness, or evaluating tumor recurrence remains to be determined in patients with squamous cell carcinoma of the head and neck. PMID- 7863933 TI - Obliteration of fat planes by perineural spread of squamous cell carcinoma along the inferior alveolar nerve. AB - Squamous cell carcinoma showed perineural spread along the inferior alveolar nerve. Key CT features of this spread were foramen enlargement, resurfacing of tumor, and asymmetry of fat spaces. PMID- 7863934 TI - Effect of dose and field strength on enhancement with paramagnetic contrast media. AB - PURPOSE: To compare contrast enhancement per unit of dose of contrast medium in MR imaging at 0.5 and 1.5 T. METHODS: Contrast enhancement in images made at 0.5 and 1.5 T after 0.1 mmol/kg of gadopentetate dimeglumine and 0.3 mmol/kg of gadodiamide was measured and the degree of contrast enhancement in the cavernous sinus and pituitary gland compared. RESULTS: At both field strengths and both contrast medium doses, contrast enhancement was noted in the cavernous sinus, pituitary gland, infundibulum, maxillary sinus mucosa, falx cerebri, and choroid plexus on inspection of images. Enhancement was significantly and conspicuously less in the cavernous sinus and pituitary gland at 0.5 T (96% and 33%, respectively) than at 1.5 T (160% and 102%, respectively). No tissues were identified that enhanced only with the larger dose or higher field strength. CONCLUSION: In tissues that normally enhance after intravenous administration of gadolinium chelates, enhancement is greater at 1.5 T than at 0.5 T. PMID- 7863935 TI - Proton MR spectroscopy of brain abnormalities in neonates born to HIV-positive mothers. AB - PURPOSE: To examine the sensitivity of proton MR spectroscopy for detecting early central nervous system abnormalities in neonates born to human immunodeficiency virus (HIV)-positive mothers. METHODS: Asleep, unsedated, and continuously monitored by electrocardiography, 10 newborns, 5 with HIV-positive and 5 with HIV negative mothers, were studied within the first 10 days of life in a 1.5-T scanner. After T1- and T2-weighted images were obtained, proton spectra were performed using voxels of interest (3.4 cm3) in the deep parietooccipital white matter. Peaks were identified as N-acetyl-aspartate (2.0 ppm), creatine and phosphocreatine (3.0 ppm), choline (3.2 ppm), and inositol (3.5 ppm). Peak areas were used to calculate metabolic ratios: N-acetyl-aspartate to creatine, inositol to creatine, and creatine to choline. RESULTS: All newborns of HIV-positive mothers had abnormal proton spectra compared with control infants; a nonspecific amino acid peak in the 2.1- to 2.6-ppm area was elevated, broad, and overlapping the N-acetyl-aspartate peak in all the HIV-exposed newborns and in only 1 of the 5 control newborns. The choline-to-creatine ratio was higher in HIV-exposed newborns at 2.3 +/- 0.4 (normal term, 0.9 +/- 0.3), as was the N-acetyl-aspartate to-creatine ratio at 2.6 +/- 0.9 (for control subjects, 1.2 +/- 0.4). MR images from these brain regions were all considered normal. Because acquired immunodeficiency syndrome develops in only a small fraction of neonates born to HIV-seropositive mothers, the above spectral abnormalities found in all our subjects may result from indirect effects of HIV, such as intrauterine growth retardation. CONCLUSIONS: These findings indicate that proton MR spectroscopy might play an important role in detecting early central nervous system complications in newborns of HIV-seropositive mothers. PMID- 7863936 TI - Craniosynostosis: diagnostic imaging with three-dimensional CT presentation. AB - PURPOSE: To measure diagnostic performance and preference of two three dimensional CT reconstruction modalities (voxel-gradient and surface-projection) displayed two ways (conventional and unwrapped) in craniosynostosis confirmed by surgical inspection and histologic analysis of resected sutures. METHODS: High resolution 2-mm contiguous CT sections were obtained and three-dimensional reconstruction images generated for 25 infants and children with skull deformities before surgical treatment of craniosynostosis. Two pediatric radiologists and two neuroradiologists first ranked images by their own preferences for diagnostic use. Then they diagnosed craniosynostosis from images presented in random order and blinded. The standard of reference was inspection during surgery and histologic evaluation of excised sutures. Finally, reviewers repeated their subjective preference tests. RESULTS: The least experienced radiologist had 100% sensitivity for all imaging modalities and specificities ranging from 43% to 83%. The two most experienced radiologists performed nearly identically, with sensitivities of 96% and specificities of 100%. After performing diagnostic tasks using all image types, all radiologists preferred conventional surface projections. CONCLUSION: Experienced readers can achieve nearly perfect diagnostic performance using the latest three-dimensional CT reconstruction images, making it a contribution to the diagnostic process. Although performance is nearly identical for all modalities, readers strongly prefer conventionally presented surface-projection images. PMID- 7863937 TI - Development of posterior fossa dural sinuses, emissary veins, and jugular bulb: morphological and radiologic study. AB - PURPOSE: To report the anatomic and radiologic development of the transverse, sigmoid, and occipital sinuses, the emissary veins, and the jugular bulb formation from the jugular sinus in humans before and after birth. METHODS: Roentgenograms of 33 injected brains showing the cranial venous system in human fetuses from 3 to 7 months of gestational age and cerebral angiograms of newborns and infants up to 6 years of age (23 clinical cases) were made and analyzed in detail. Special attention was focused on the inner diameters of the transverse and sigmoid sinuses and of the internal jugular veins, particularly at the sigmoid sinus-internal jugular vein junction. RESULTS: Marked increase in venous flow from the rapidly growing cerebral hemispheres leads to ballooning of the transverse sinuses in the absence of an increase in the inner diameters of the sigmoid and jugular sinuses. The ballooning also results in formation of the occipital sinus, marginal sinus around the foramen magnum, and emissary veins. The formation of the jugular bulbs from the jugular sinuses begins after birth when a shift from a fetal to a postnatal type of circulation (or from a lying down position to an erect posture) takes place. CONCLUSION: The morphological changes of the posterior fossa dural sinuses, emissary veins, and jugular bulb are closely related to the development of the brain, shift to postnatal type of circulation, and postural hemodynamic changes. PMID- 7863938 TI - Use of thallium-201 brain SPECT to differentiate cerebral lymphoma from toxoplasma encephalitis in AIDS patients. AB - PURPOSE: To determine whether thallium-201 brain single-photon emission CT could be used to make the distinction between central nervous system lymphoma and toxoplasma encephalitis, which may not be possible by routine MR and CT. METHODS: A total of 37 patients with acquired immunodeficiency syndrome who had intracranial mass lesions found during a 9-month prospective study by either MR or CT underwent further evaluation with Tl-201 brain single-photon emission CT. RESULTS: Twelve patients had increased intense focal Tl-201 uptake. All of these patients had either biopsy- or autopsy-proven lymphoma. Twenty-five of the patients studied had no Tl-201 brain uptake in the lesion(s); 24 of these patients had toxoplasma encephalitis on clinical follow-up. One patient with no Tl-201 uptake was found by cerebrospinal fluid analysis to have mycobacterium tuberculosis abscess. CONCLUSION: Patients with acquired immunodeficiency syndrome who have intracranial mass lesions on MR or CT may benefit from Tl-201 brain single-photon emission CT because it can help distinguish between lymphoma and infectious lesions such as toxoplasma encephalitis. PMID- 7863939 TI - Acute spinal subdural hematoma: MR and CT findings with pathologic correlates. AB - PURPOSE: To determine the MR and CT findings that characterize acute spinal subdural hematoma (ASSH). METHODS: The MR, CT, and clinical findings in three patients with surgically proved ASSH were reviewed and also correlated with the postmortem MR, CT, and cryomicrotome findings in three other patients, two with ASSH and one with an acute spinal epidural hematoma. RESULTS: Imaging findings in ASSH included: (a) hyperdense lesions on plain CT within the dural sac, distinct from the adjacent low-density epidural fat and silhouetted against the lower density spinal cord and cauda equina, which it compressed; (b) lack of direct continuity with the adjacent osseous structures; (c) clumping, loculation, and streaking of blood within the dural sac on both MR and Ct; and (d) an inhomogeneous and variable signal intensity to the ASSH on all MR pulse sequences, but, nevertheless, a striking low signal intensity on T2-weighted spin echo or T2-weighted gradient-echo to a major part of the ASSH because of deoxyhemoglobin. Plain CT was most helpful in compartmentalizing the hematoma. CONCLUSION: When MR and plain CT are obtained as complementary studies, they provide characteristic findings that allow the prompt diagnosis of ASSH. PMID- 7863940 TI - Enhancement of intervertebral disks with gadolinium complexes: comparison of an ionic and a nonionic medium in an animal model. AB - PURPOSE: To compare MR contrast enhancement of intervertebral disk tissue after intravenous administration of equimolar doses of an ionic and of a nonionic gadolinium complex. METHODS: Contrast enhancement was measured on MR in lumbar intervertebral disks for 120 minutes after intravenous injection of gadoteridol or gadopentetate dimeglumine, 0.3 mmol/kg. MR studies were performed with each contrast medium in four rabbits. Contrast enhancement was measured in intervertebral disks as a function of time and contrast medium. RESULTS: With both contrast media, enhancement of normal intervertebral disks was detected. Enhancement of disks was significantly greater with gadoteridol than with gadopentetate dimeglumine. CONCLUSION: The enhancement of cartilage is influenced by the molecular structure of the gadolinium complex. The negative charge of gadopentetate dimeglumine may give it a slower rate of diffusion into disk cartilage than a nonionic complex. PMID- 7863941 TI - Lupus-related myelitis: serial MR findings. AB - PURPOSE: To correlate the MR findings in transverse myelitis secondary to systemic lupus erythematosus with clinical findings during disease exacerbation and remission. METHODS: Four patients (ages 33 to 47 years) with episodes of transverse myelitis secondary to systemic lupus erythematosus were identified. Three patients had recurrent transverse myelitis episodes (one patient with two recurrences), for a total of eight episodes. MR examinations (six after contrast administration) were performed during each transverse myelitis episode, as well as during four periods of remission (in three patients) after therapy with steroids and/or immunosuppressive agents. MR examinations were reviewed for the presence of spinal cord enlargement, intramedullary signal abnormality, and contrast enhancement. RESULTS: Prolongation of T1 or T2 signal (or both) was seen in eight episodes (100%). Spinal cord enlargement was seen in six (75%) of eight transverse myelitis episodes, although it was mild during two episodes. Contrast enhancement was seen in three of six transverse myelitis episodes (dense, inhomogeneous enhancement during two episodes in one patient, and a small focus of enhancement in one patient). During periods of remission, spinal cord diameter returned to normal, and no contrast enhancement was seen, although abnormal signal was present in three examinations performed within 2 months of a transverse myelitis episode. CONCLUSION: Spinal cord widening and signal abnormalities are common MR findings during episodes of transverse myelitis related to systemic lupus erythematosus, and contrast enhancement is less frequently seen. Improvement or resolution of these findings correlates with clinical improvement. PMID- 7863942 TI - MR in Toxocara canis myelopathy. AB - We present the case of a 23-year-old woman with cerebrospinal fluid eosinophilia and myelopathy caused by Toxocara canis and describe the clinical and thoracic MR findings. An enhancing thoracic spinal cord lesion which was shown on MR resolved after an interval of 140 days with partial resolution of the patient's symptoms. PMID- 7863943 TI - Demyelinating and gliotic cerebellar lesions in Langerhans cell histiocytosis. AB - PURPOSE: To describe the involvement of the cerebellum by a gliotic and demyelinating process in Langerhans cell histiocytosis. METHODS: A retrospective analysis of all (N = 30) cases of Langerhans cell histiocytosis followed at our institution since 1975 yielded four patients with CT and/or MR evidence of cerebellar abnormalities. RESULTS: Four patients manifested strikingly similar findings of symmetric nonenhancing hypodensities in the dentate nuclei region of the cerebellum, which were hypointense on short-repetition-time/short-echo-time MR and hyperintense on long-repetition-time/long-echo-time MR. Biopsy in one patient yielded areas of demyelination, cell loss, and gliosis without histiocytic infiltration. CONCLUSION: Langerhans cell histiocytosis involves the cerebellum in a specific and poorly understood manner. Lesions on imaging may precede clinical findings by years. Lesions may occur in patients who have never experienced radiation therapy and may act as a marker for eventual central nervous system deterioration. PMID- 7863944 TI - Serial MR after bone marrow transplantation in two patients with metachromatic leukodystrophy. AB - Two children with metachromatic leukodystrophy underwent bone marrow transplantation. In both patients MR subsequently showed, first, white matter changes, then later, lack of change as the patients stabilized clinically. PMID- 7863945 TI - A simple practical classification of cerebral infarcts on CT and its interobserver reliability. AB - PURPOSE: To test the interobserver reliability of a simple method of classifying cerebral infarcts as seen on CT brain scans, which might allow differentiation of the site and size of the infarct from infarct swelling and hemorrhagic transformation. METHOD: Two experienced neuroradiologists independently reviewed 119 CT brain scans showing recent small to large cortical and subcortical cerebral infarcts and classified each for site and size, amount of swelling, and hemorrhagic transformation blind to clinical information. Six less experienced general radiologists in training classified 33 of the CT scans blind to clinical information. Interobserver agreement was calculated using unweighted kappa statistics. RESULTS: The kappa statistics between the two experienced neuroradiologists were: (a) 0.78 for site and size (95% confidence interval 0.69 0.87); (b) 0.8 for swelling (95% confidence interval, 0.68-0.92); and (c) 0.3 for hemorrhagic transformation (95% confidence interval, 0-0.77); indicating "good," "excellent," and "fair" agreement, respectively. Agreement for the less experienced radiologists was fair to excellent. CONCLUSION: The cerebral infarct morphologic classification is simple, quick, and reliable and therefore practical. It usefully distinguishes between infarcts of similar site and size but with different amounts of swelling and hemorrhagic transformation, thus facilitating study of factors such as the influence of drug treatment on infarct swelling, which might influence clinical outcome. Although developed for CT, it could be used equally for MR imaging and has applications in research and clinical practice. PMID- 7863946 TI - MR of acute subarachnoid hemorrhage: a preliminary report of fluid-attenuated inversion-recovery pulse sequences. AB - We report preliminary results applying fluid-attenuated inversion-recovery (FLAIR) sequences to three patients with acute subarachnoid hemorrhage. Acute subarachnoid hemorrhage could be clearly demonstrated as areas of high signal intensity on FLAIR sequences in all patients. These preliminary results suggest that with FLAIR sequences one could reliably diagnose acute subarachnoid hemorrhage. PMID- 7863947 TI - Rotational angiography assessment of cerebral aneurysms. AB - PURPOSE: To compare rotational angiography with conventional digital subtraction angiography in the assessment of cerebral aneurysms. METHODS: Conventional digital subtraction angiography and rotational angiography were compared in 57 patients investigated for the preoperative diagnosis of subarachnoid hemorrhage and in 13 patients after surgery. Images were compared for location, visibility of the aneurysmal neck, vascular branch anatomy, projection, size, presence of spasm, and shape of the aneurysm. RESULTS: Rotational angiography was superior to the digital angiogram in assessing aneurysms and vascular anatomy in the following percentage of cases: 12% for location, 46% for the presence of a neck, 32% in the assessment of branch anatomy, 19% for projection, 12% for size, 3.5% for spasm, and 19% for shape. After surgery, rotational angiography more clearly demonstrated the presence or absence of a neck in 69% of the cases. CONCLUSIONS: Rotational angiography often allows better visualization of vascular anatomy and therefore improves the angiographic assessment of aneurysms when compared with conventional digital subtraction angiography, making it an excellent adjunct in the investigation of subarachnoid hemorrhage. The lack of subtraction artifacts from the surgical clips and multiple angles of view also allow better assessment of the presence or absence of a residual neck in postoperative cases. PMID- 7863948 TI - MR of mandibular invasion in patients with oral and oropharyngeal malignant neoplasms. AB - PURPOSE: To investigate whether MR imaging is an accurate means of assessing mandibular invasion in patients with carcinoma. METHODS: We retrospectively studied the MR scans of 22 patients with pathologic or surgical confirmation of mandibular invasion from oral and oropharyngeal cancers. The MR images were blindly analyzed using primary criteria of: (a) cortical breakdown, (b) replacement of bone marrow fat, or (c) gadopentetate dimeglumine enhancement of a mass at the bone marrow defect. Secondary criteria of: (a) contiguous soft-tissue mass, and (b) mass on both sides of the mandibular cortex were also examined. Mandibular invasion was graded as periosteal/cortical, medullary, or no invasion. RESULTS: Primary positive findings of cortical breakdown and abnormal bone marrow signal were highly sensitive (100%) for periosteal/cortical invasion and medullary involvement, respectively. However, a high rate of false-positive studies hampered the MR accuracy, which fell into the 73% to 77% range. A negative MR study was highly predictive, but a positive study was less valuable. Gadolinium enhancement added little to the MR study's accuracy. False-positive studies mainly occurred in the setting of prior irradiation, osteoradionecrosis, and odontogenic infections. CONCLUSIONS: MR imaging is a sensitive method for detecting mandibular invasion but has a low positive predictive value. A negative study virtually excludes cortical/periosteal or bone marrow invasion. PMID- 7863949 TI - Intracerebral schwannoma: CT and MR findings. AB - A case of intracerebral schwannoma in a 19-year-old man is reported. CT and MR findings were nonspecific, suggesting a primary glioma. The histologic features were of schwannoma. PMID- 7863950 TI - Cystic meningiomas: MR characteristics and surgical correlations. AB - PURPOSE: To describe the MR appearance of cystic meningiomas, and to correlate the MR appearance with the surgical and neuropathologic findings. METHODS: Eight patients with cysts associated with meningiomas were studied on a 1.5-T MR system. Unenhanced sagittal T1- and axial T2-weighted images were obtained in all patients. Axial and coronal gadopentetate dimeglumine-enhanced T1-weighted spin echo images were obtained in seven patients. Additional sagittal T1-weighted spin echo contrast-enhanced images were obtained in four patients. RESULTS: The cystic components were intratumoral and eccentric in two cases, intraparenchymal in one case, and extraparenchymal (trapped cerebrospinal fluid) in five cases. Cyst wall enhancement was present in two of seven cases performed with intravenous gadopentetate dimeglumine. There was no correlation between cyst signal intensity and cyst content. A preoperative diagnosis of cystic meningioma was possible in all eight cases. CONCLUSIONS: MR demonstrates the extradural location of the tumor and its cystic component, correlates well with the surgical presentation and the neuropathologic results, and allows the preoperative diagnosis of cystic meningioma based on the MR findings. Division into three types of cysts aids the neurosurgeon, who must decide whether total resection is feasible. To obtain total resection and reduce the risk of recurrence with an intratumoral cyst, the surgeon must ensure that the plane of resection is in fact between the thin enhancing membrane of the tumor cyst and the adjacent arachnoid. In cases in which the cyst is trapped cerebrospinal fluid or intraparenchymal in location, the cyst wall adjacent to or within the brain parenchyma is not included in the resection. PMID- 7863951 TI - Pitfall of MR in a patient with spinal ependymoma and drop metastasis. PMID- 7863952 TI - Total intravenous anesthesia with propofol in pediatric patients for MR examination. PMID- 7863953 TI - Application of stereoscopic viewing to maximum intensity projection images obtained in MR angiography. PMID- 7863954 TI - Fluid-blood levels in intracerebral hemorrhage. PMID- 7863955 TI - Annotated bibliography. PMID- 7863956 TI - The 'back-to-sleep' campaign against SIDS. PMID- 7863957 TI - Acute knee injuries: Part I. History and physical examination. AB - A thorough history and physical examination are helpful in the diagnosis of meniscal damage, cruciate and collateral ligament sprains and patellar instability, the four major acute knee injuries. When performing a physical examination in a patient with a knee injury, the uninjured knee should always be assessed first and used for comparison. Examination includes passive and active range-of-motion testing, palpation of the joint line spaces, and a variety of maneuvers to evaluate knee stability. Valgus and varus testing provides assessment of the collateral ligaments. The Lachman and pivot shift tests are useful in the evaluation of the anterior cruciate ligament. The posterior drawer and tibial sag tests are used to evaluate the posterior cruciate ligament. The bounce test, McMurray's test and Apley's grind test can aid in the diagnosis of meniscal injury. PMID- 7863958 TI - New cutaneous manifestations of systemic diseases. AB - In recent years, especially with the advent of acquired immunodeficiency syndrome, new skin disorders associated with systemic disease have been described in the literature. Eosinophilic folliculitis and pruritic papules of human immunodeficiency virus (HIV) infection are clinically similar lesions that respond to phototherapy. Bacillary angiomatosis, another HIV-related skin disease that is caused by a pleomorphic gram-negative organism, resembles Kaposi's sarcoma clinically but is curable if treated early with antibiotics. Toxic strep syndrome, a scarlatiniform, desquamative eruption associated with hypotension, fever and multiorgan system dysfunction, is caused by group A streptococcal soft tissue infection. Paraneoplastic pemphigus, a recently characterized autoimmune vesicular eruption, produces painful mucocutaneous ulcerations in patients with an occult neoplasm, such as chronic lymphocytic leukemia or malignant lymphoma. PMID- 7863959 TI - Cognitive and functional impairment. U.S. Public Health Service. PMID- 7863960 TI - Vaginal bleeding in pregnancy. AB - The process of identifying and evaluating the common causes of vaginal bleeding during pregnancy changes as the pregnancy progresses to term. The most common identifiable causes of vaginal bleeding during early pregnancy include spontaneous abortion and ectopic pregnancy. Pelvic ultrasound and quantitative beta-human chorionic gonadotropin measurements are used in the evaluation of early-stage bleeding in pregnancy. During the middle and late stages of pregnancy, placental abnormalities become important in the differential diagnosis of vaginal bleeding. Placenta previa classically presents as painless bleeding and is evaluated with ultrasound. Patients with placental abruption may present with abdominal pain and bleeding. As pregnancy progresses to term, bloody show must be considered as a common source of bleeding. Vaginal and cervical lesions can cause vaginal bleeding in any stage of pregnancy. PMID- 7863961 TI - Sleepwalking. AB - Sleepwalking is one of the parasomnias, a group of disorders that also includes night terrors, nocturnal enuresis and nightmares. This disorder of arousal is much more common in children than in adults, and it is commonly associated with other parasomnias. Sleepwalking typically occurs during the first three hours of sleep, when sleep stages 3 and 4 (non-rapid-eye-movement sleep) are most prevalent. The episodes usually last 30 seconds to 30 minutes. The differential diagnosis of sleepwalking includes partial complex seizures occurring during sleep, rapid-eye-movement behavior disorder, night terrors, malingering, dissociative phenomena and medication effects. The treatment of sleepwalking in children includes providing a regular sleep-wake schedule, ensuring that the child has sufficient sleep and reassuring the parents. Medications and psychotherapy may be indicated in some adult patients. PMID- 7863962 TI - American Association of Clinical Endocrinologists releases clinical guidelines for thyroid disease. PMID- 7863963 TI - Factors involved in the development of symptom-producing atherosclerotic plaques. PMID- 7863964 TI - Proceedings of the Atherothrombosis Advisory Meeting. Palm Beach, Florida, January 28-29, 1994. PMID- 7863965 TI - Thrombin hypothesis of thrombus generation and vascular lesion formation. AB - Thrombin plays a central role in vascular lesion formation. It is the principal mediator of thrombogenesis, which is interrupted when direct antithrombins (including hirudin and its synthetic peptide analogs), thrombin receptor antagonist peptides, or thrombin generation inhibitors (including active-site inhibited factor VIIa, recombinant tick anticoagulant peptide, and omega-3 fatty acids) are used to block thrombin. Thrombin is also a potent growth factor, initiating smooth muscle cell proliferation at injury sites. In baboons, this reaction is 80% reduced by hirudin (p < 0.01). Thrombin also plays a role in modulating the effects of other growth factors such as platelet-derived growth factor (PDGF). Thus, Phe-Pro-Arg-CH2Cl prevents expression in baboons of PDGF-A mRNA induced by vascular injury due to balloon angioplasty; untreated mechanical injury results in a 3-fold increase in PDGF-A mRNA expression. Thrombin also regulates inflammatory processes, inducing expression both of leukocyte adhesion molecules and of their counterreceptors by endothelium. PMID- 7863966 TI - Activation of blood coagulation by plaque rupture: mechanisms and prevention. AB - Inhibition of thrombosis is proving to be an important treatment goal in many clinical situations, including coronary thrombolysis, angioplasty, and unstable angina. Heparin is a potent inhibitor of thrombin and thrombin generation, but its ability to accelerate thrombolysis, prevent acute reocclusion after vascular injury in angioplasty, and prevent myocardial infarction in unstable angina is relatively limited, possibly because clot-bound thrombin plays an important role in these clinical situations. Thus, when thrombin binds to fibrin, it remains enzymatically active and relatively impervious to inactivation by heparin or other fluid-phase inhibitors. However, direct thrombin inhibitors--such as D-Phe L-Pro-L-Arg-CH2Cl (PPACK), hirudin, hirugen, and hirulog--inhibit free and clot bound thrombin with equal efficacy, presumably because their sites of interaction are not masked when thrombin binds to fibrin. Advanced clinical trials suggest that the direct thrombin inhibitors and 7E3, an inhibitor of platelet glycoprotein IIb/IIIa, will soon be incorporated into the armamentarium against arterial thrombosis. PMID- 7863967 TI - Combined use of aspirin and warfarin in primary prevention of ischemic heart disease in men at high risk. AB - The combination of aspirin and warfarin is likely to be more effective than either agent alone in the prevention of ischemic heart disease (IHD), but its practical value also crucially depends on a low incidence of serious bleeding. The occurrence of bleeding of different degrees of severity is being established in the Thrombosis Prevention Trial of primary prevention in men aged 45-69 years at increased risk of IHD, in which 75 mg aspirin and warfarin dosed to an international normalized ratio of 1.5 are used in a factorial design. The annual risk of serious bleeding, i.e., requiring transfusion or surgery, may be about 1 in 500 for those on active treatment, whether this consists of both aspirin and warfarin or either alone. Less serious degrees of bleeding are significantly increased by the combination of aspirin and warfarin compared with either alone and by either alone compared with placebo. The risk of serious bleeding is probably acceptable if low dosages are used. PMID- 7863968 TI - Novel antithrombotic approaches to coronary artery disease. AB - Current prevention or treatment of coronary thrombosis relies on antiplatelet agents (aspirin), antithrombin agents (heparin), and plasminogen activators (t PA). The purpose of this review is to describe novel antithrombotic agents in each of these classes and to discuss recent and future clinical trials with the new agents. Whereas aspirin is a cyclo-oxygenase inhibitor, the most promising new antiplatelets are directed at an integrin cell surface receptor--glycoprotein (GP) IIb/IIIa--which represents the final common pathway for platelet aggregation. The monoclonal F(ab) antibody c7E3, a chimeric murine-human immunoglobulin G (IgG) fragment, is the most intensively studied to date. c7E3 was assessed by the Evaluation of Platelet Monoclonal Antibody to Prevent Ischemic Complications (EPIC) trial in which 2,099 high-risk angioplasty patients were randomized to bolus (placebo) plus infusion (placebo), bolus (c7E3, 0.25 mg/kg) plus infusion (placebo), and bolus (c7E3, 0.25 mg/kg) plus infusion (c7E3, 10 micrograms/min; 12 hours). The overall event rate at 30 days was significantly decreased from 12.8% (placebo) to 8.3% (c7E3), a 36% relative reduction (p = 0.009). Integrelin is a cyclic heptapeptide with marked specificity for GP IIb/IIIa integrin. It was studied during the Integrelin to Manage Platelet Aggregation to Prevent Coronary Thrombosis (IMPACT) trial, which enrolled 150 routine coronary intervention patients. At endpoint, overall event rate was reduced from 11.9% (placebo) to 5.6% (integrelin). The much larger (4,010 patients) IMPACT-II trial has just completed enrollment to confirm and extend these encouraging results. Hirudin is the prototype of the direct antithrombins; it binds to the active catalytic site and the substrate recognition site (exosite) of thrombin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863969 TI - Role of thrombosis in atherosclerosis and its complications. AB - The endothelium is intact but activated and dysfunctioning during the early phase of atherogenesis. Owing to increased endothelial permeability, many blood-derived components, including hemostatic factors, are present in early as well as advanced atherosclerotic lesions. Insudated fibrin(ogen) and related degradation products and thrombin could contribute to atherogenesis by their chemotactic (attracting monocytes/macrophages) and mitogenic (stimulating cell proliferation) properties. All key cells in plaque may express thrombin receptors, indicating that thrombin may play a role in the genesis of uncomplicated atherosclerosis by mediating inflammatory and proliferative processes. Later, endothelial denudation with platelet adherence occurs over mature plaques. Then, incorporation of microthrombi and probably platelet/thrombus-derived growth factors are critical for the progressive growth of the smooth muscle cell-related plaque component. Besides transendothelial influx and incorporation of mural thrombi, blood products in atherosclerotic plaques may originate from hemorrhage through a ruptured plaque surface or from fragile newly formed vessels (neovascularization) frequently found at the base of advanced plaques. Rupture-related plaque progression due to luminal thrombosis and/or plaque hemorrhage is the most important mechanism underlying the unpredictable rapid progression of coronary lesions responsible for acute coronary syndromes. Both platelets and fibrin play a role in the dynamic thrombotic response to plaque rupture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863970 TI - Thrombosis. PMID- 7863971 TI - Antithrombotic agents in cerebral ischemia. AB - The choice of antithrombotic agent in cerebral ischemia depends on the pathogenesis: thrombosis, embolism, or hemorrhage. Antiplatelet agents are considered most beneficial in thrombotic stroke, anticoagulants are most effective in cardioembolic stroke; antithrombotic agents are generally contraindicated in hemorrhagic stroke. A meta-analysis of 18 trials documented a 23% reduction in stroke risk with antiplatelet agents; aspirin is typically the antiplatelet agent of choice for stroke prevention. There are no definitive data regarding the optimal aspirin dose for stroke prevention and this issue remains controversial. Ticlopidine is the most effective antiplatelet agent, but its adverse effect profile restricts its use. Anticoagulants are highly effective for preventing cardioembolic stroke, but their effectiveness in non-cardioembolic stroke is uncertain because of lack of trial data. Results of the ongoing Warfarin/Aspirin Recurrent Stroke Study (warfarin [INR 1.8-2.8] vs aspirin [325 mg/day]) may clarify this issue. There is renewed interest in thrombolytics because recent data indicate that reperfusion within a few hours of stroke onset appears to be effective in preventing neuronal damage. In addition, when given within 6 hours of stroke onset, thrombolytics appear to be relatively safe. Several direct thrombin inhibitors are being evaluated. Experimentally, hirudin, hirulog, D-Phe-L-Pro-L-Arg-CH2Cl (PPACK), and argatroban are clearly more effective than heparin in inhibiting platelet deposition and thrombus formation, and also show promise in preventing reocclusion after thrombolysis for both experimental thrombotic and embolic stroke. However, the risk of hemorrhage in patients with cerebrovascular disease is unknown for these agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863972 TI - Optimal intensity and monitoring warfarin. AB - The risk of bleeding with warfarin can be markedly reduced without affecting efficacy by using a low-intensity therapeutic range. The reliability of warfarin monitoring has also improved with the development of the international normalized ratio (INR) to standardize prothrombin time despite use of nonuniform thromboplastins by different laboratories. There are 2 recommended therapeutic ranges of intensity for warfarin: the less intense corresponds to INR 2.0-3.0, the more intense, to INR 2.5-3.5. Dosage response to warfarin is influenced by concomitant medication, dietary vitamin K, hepatic dysfunction, and hypermetabolic states. For rapid anticoagulant effect, the initial dosage is 10 mg/day (plus heparin). For nonemergent treatment, the initial dosage is 4-5 mg/day, which achieves a steady-state anticoagulant effect in 5-7 days; this is also the anticipated maintenance dosage. Prothrombin time (PT) monitoring is performed daily until the therapeutic range is achieved, then progressively less often, depending on stability of PT results. Bleeding while on warfarin (INR > 3.0) may respond to reduced dosage; for severe bleeding, vitamin K reverses warfarin effects in 6-12 hours. Bleeding on low-intensity warfarin (INR < 3.0) suggests an underlying pathologic condition. Warfarin is contraindicated in pregnancy because of its teratogenicity but may be used by nursing mothers, as it does not pass into breast milk. PMID- 7863973 TI - Lipids. PMID- 7863974 TI - Atherogenic dyslipidemia: lipoprotein abnormalities and implications for therapy. AB - Atherogenic dyslipidemia is a lipoprotein profile combining 4 specific abnormalities: borderline-high total cholesterol levels; high triglyceride concentrations; small, dense, low-density lipoprotein (LDL) particles; and low high-density lipoprotein (HDL) concentrations. It is a predisposing factor to premature coronary artery disease (CAD), although separating and calculating the contribution of each abnormality to the risk of CAD is difficult, especially since the abnormalities often appear in this combination. The ratio of total cholesterol to HDL cholesterol is currently the most powerful single predictor of risk in dyslipidemic patients. Therapy for atherogenic dyslipidemia includes dietary changes aimed at decreasing intake of cholesterol-raising fatty acids and achieving weight reduction; exercise, which confers many of the benefits of weight reduction; and, when those measures fail to correct the lipid and lipoprotein profile, drug therapy. Nicotinic acid reduces triglyceride and cholesterol levels while raising HDL concentrations, but up to half of patients cannot tolerate its adverse effects. Fibric acids effectively lower triglyceride levels and are generally well tolerated but have little beneficial effect on the cholesterol profile. Statins offer marked reductions in total, LDL, and very low density lipoprotein cholesterol levels and cause modest increases in HDL concentration. Combination therapy can enhance the efficacy of the individual drugs. PMID- 7863975 TI - Dense low density lipoproteins and coronary artery disease. AB - A common, genetically influenced lipoprotein subclass profile characterized by a predominance of small, dense low density lipoprotein (LDL) particles is associated with relative increases in plasma triglyceride and apolipoprotein (apo) B-100, and reduced levels of high density lipoprotein cholesterol and apoAI. Recently, this phenotype has also been associated with the insulin resistance syndrome and familial combined hyperlipidemia. Case-control studies of patients with myocardial infarction and angiographically documented coronary artery disease (CAD) have demonstrated that 40-50% of patients have the small, dense LDL phenotype and that this is associated with a 2- to 3-fold increase in disease risk. However, because of strong statistical correlations among the multiple features of the phenotype, it has been difficult to determine whether > or = 1 of its metabolic alterations are primarily responsible for increased CAD susceptibility. More direct evidence for enhanced atherogenicity of lipoproteins in this trait derives from a recent report that LDL-cholesterol lowering by diet and drug treatment resulted in reduced coronary angiographic progression in CAD subjects with predominantly dense LDL, but that an equivalent lowering of LDL cholesterol in subjects with more buoyant LDL was not associated with angiographic benefit. Further, in vitro findings have indicated increased susceptibility of small, dense LDL to oxidative modification and relatively greater binding of these particles to arterial wall proteoglycans. Thus, the small, dense LDL trait may underlie familial predisposition to CAD in a large proportion of the population, and its presence may indicate the potential for benefit from specific therapeutic interventions. PMID- 7863976 TI - Identification of mutations in human apolipoprotein(a) kringle 4-37 from the study of the DNA of peripheral blood lymphocytes: relevance to the role of lipoprotein(a) in atherothrombosis. AB - Using a technique that amplifies the DNA region coding for kringle 4-37 of human apolipoprotein(a) we have identified 2 mutations, trp72-->arg and met66-->thr. The former was only present in 2 of the 100 subjects studied, was associated with a lysine-binding defective lipoprotein(a) [Lp(a)], low plasma levels of Lp(a), and no evidence of atherosclerotic cardiovascular disease (ASCVD). The other mutation was present in about 40% of the subjects who had either normal or high plasma levels of Lp(a) and a personal and/or familial history of ASCVD. These studies show that human kringle 4-37 is mutable and that mutations in this kringle can affect the lysine-binding properties of apo(a) and, perhaps, the atherothrombogenic potential of Lp(a). PMID- 7863977 TI - The vessel wall. PMID- 7863978 TI - Genetic control of the inflammatory response induced by oxidized lipids. AB - The fatty streak begins with entrapment of apolipoprotein B (apoB)-containing lipoproteins in the subendothelial space at susceptible sites in the arterial wall. Minimally oxidized low density lipoprotein (MM-LDL) induces endothelial cells to bind monocytes and produce message and protein for monocyte chemotactic protein-1 and macrophage colony-stimulating factor. In culture, human endothelial and smooth muscle cells in arterial wall configuration sequester LDL, protecting it from antioxidants and giving rise to MM-LDL-like species. In mice, MM-LDL induces monocyte binding at susceptible aortic sites; the monocytes may then differentiate into macrophages that release reactive oxygen and active aldehydes, resulting in highly oxidized LDL leading to foam cell formation. Feeding mice an atherogenic diet induces expression of several inflammatory and oxidative stress genes, including serum amyloid A, which binds exclusively to HDL. This may contribute to a decrease in protective HDL levels seen in mice susceptible to fatty streak formation. PMID- 7863979 TI - Systemic nature of endothelial dysfunction in atherosclerosis. AB - Vascular endothelium plays a pivotal role in the maintenance of vasodilation and the inhibition of platelet aggregation and smooth muscle cell proliferation through the release of nitric oxide and other factors. Extensive data have demonstrated abnormalities in coronary endothelial function in the epicardial coronary arteries in patients with atherosclerosis or risk factors for atherosclerosis. This dysfunction leads to abnormal vasoconstriction and platelet aggregation, which likely play a role in producing ischemia in patients with coronary artery disease. Invasive techniques have been available to assess endothelium-dependent vasodilator responses in the coronary arteries. However, until recently little has been known about endothelial responses in the peripheral vasculature, as methods to assess this have not been readily available. The hypothesis that endothelial dysfunction is a systemic process is explored, and new noninvasive methods of assessing endothelial function are discussed. PMID- 7863980 TI - Physiologic consequences of increased vascular oxidant stresses in hypercholesterolemia and atherosclerosis: implications for impaired vasomotion. AB - During the past 8 years, it has become apparent that endothelium-dependent vascular relaxation is abnormal in a variety of disease states, including hypercholesterolemia, atherosclerosis, diabetes, hypertension, and following heart transplantation. Our laboratory and several others have examined dysfunctional regulation of vasomotor tone in hypercholesterolemia and atherosclerosis. These studies have led to the concepts that altered regulation of vasomotion by the endothelium (1) is an early development in atherosclerosis, (2) involves both large vessels (with overt atherosclerosis) and the microcirculation (in which atherosclerosis does not develop), and (3) can be reversed by lipid-lowering strategies. The mechanisms for the abnormalities underlying this form of endothelial dysfunction are likely multifactorial, but a major underlying factor appears to be increased oxidant degradation of endothelium-derived nitric oxide. In this review we examine the evidence supporting this conclusion and consider the implications of these findings. PMID- 7863981 TI - Role of the thrombin receptor in restenosis and atherosclerosis. AB - Thrombus generation is central to thrombosis at vascular lesion sites, including post-PCTA acute reocclusion and chronic restenosis. Thrombin stimulates platelet activation, monocyte and neutrophil chemotaxis, and endothelial production of prothrombotic factors. The varied physiologic effects of thrombin are due to the widespread presence of thrombin receptors in many cell types. The receptor is uniquely activated: thrombin binds to the receptor at the thrombin anion-binding exosite, the receptor ligand ("tethered ligand") apparently being a sequence of 6 amino acids (SFLLRN). Thus, peptides corresponding to the sequence of the tethered ligand can stimulate almost all functions of native thrombin itself. Several intracellular signaling pathways have been identified as important in the restenosis process: the G protein-related pathway, cyclic adenosine monophosphate (cAMP) mediator pathway, and tyrosine kinase activation pathway. In situ hybridization has demonstrated an increase in thrombin receptor mRNA throughout the period of neointimal and vascular lesion development. The mechanism of this increase is unknown, but may be mediated by multiple inflammatory modulators. Several strategies have been tested in animal models for inhibiting thrombin: (1) Hirudin not only prevents thrombin from cleaving fibrinogen, but also prevents thrombin receptor activation. (2) Thrombin receptor antagonist peptides block platelet aggregation effects of thrombin. (3) Mono- and polyclonal antibodies inhibit thrombin receptor activation. (4) Antisense oligonucleotides block thrombin receptor expression. PMID- 7863982 TI - Atherosclerotic calcification: relation to developmental osteogenesis. AB - Calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone, including trabeculae, lacunae, and areas resembling marrow. Possible mechanisms for bone formation in artery walls are developmental retention of pluripotent cells or osteoblastic immigration coupled with loss of molecular regulatory control that unmasks an embryonic osteogenic program. In situ hybridization of calcified human atherosclerotic lesions shows expression of bone morphogenetic protein type 2, a potent osteogenic differentiation factor. Medial cells of bovine aorta cultured (Dulbecco's modified Eagle's medium plus 15% fetal calf serum) for > 2 weeks form nodules similar to those formed by cultured osteoblasts, including the elaboration of hydroxyapatite. PMID- 7863983 TI - Relations between Doppler tracings of pulmonary regurgitation and invasive hemodynamics in acute right ventricular infarction complicating inferior wall left ventricular infarction. AB - To test the hypothesis that flow characteristics from pulmonary regurgitation (PR) can predict right ventricular (RV) involvement in patients with inferior wall acute myocardial infarction, we prospectively recorded continuous-wave Doppler tracings and right-sided cardiac hemodynamics in 48 consecutive patients with inferior wall acute myocardial infarction and PR. Right heart hemodynamics enabled the identification of 29 patients with (group 1) and 19 without (group 2) RV involvement. In patients with RV involvement, the pulmonary regurgitant flow pattern was characterized by a rapid rise in flow velocity to a peak level followed by an abrupt deceleration in mid-diastole, whereas in patients without RV involvement, the deceleration in mid-diastole was gradual. The pressure half time of PR (PHTPR) and the lowest mid-diastolic to peak early diastolic velocity ratio were significantly lower in group 1 than in group 2 (91 +/- 31 vs 214 +/- 57 ms [p < 0.001], 0.35 +/- 0.08 vs 0.59 +/- 0.13 [p < 0.001], respectively). The best diagnostic accuracy (95%) was obtained with cut-off values of PHTPR < or = 150 ms and the lowest mid-diastolic to peak early diastolic velocity ratio < or = 0.5: sensitivity 100%, specificity 89%, positive predictive value 94%, and negative predictive value 100%. Using multiple logistic regression analysis, we found that PHTPR was the strongest predictor of RV involvement. Thus, these parameters, derived from pulmonary regurgitant tracings, are useful in the noninvasive bedside diagnosis of RV infarction. PMID- 7863984 TI - Does the induction of ventricular flutter or fibrillation at electrophysiologic testing after myocardial infarction have any prognostic significance? AB - This study examines the significance of inducing sustained ventricular fibrillation (VF) or ventricular flutter by programmed stimulation after infarction. Programmed ventricular stimulation was performed for prognostic reasons from the right ventricular apex at twice diastolic threshold using a protocol containing 4 extrastimuli. Of 502 patients tested 11 +/- 4 days after acute infarction, VF was induced in 164 (33%), ventricular flutter in 134 (27%), ventricular tachycardia (VT) in 44 (9%), and no arrhythmia in 160 (32%). All groups were similar in age, sex distribution, and sites of index infarction. Those with inducible VT had a higher incidence of multiple infarctions and a lower mean left ventricular ejection fraction at the time of testing. Without antiarrhythmic drug therapy, 8 patients (18%) with inducible VT experienced spontaneous VT or died instantaneously during the first year of follow-up. By contrast, only 1 (0.6%) patient with inducible VF, 1 (0.7%) with ventricular flutter, and 1 (0.6%) without any inducible arrhythmias experienced similar events in the same period (p < 0.001). By relating the cycle length of the induced monomorphic arrhythmia to later spontaneous electrical events, induced arrhythmias with cycle length as low as 230 ms still identified patients at high risk for spontaneous arrhythmias. Only the induction of sustained monomorphic VT with a cycle length > 230 ms indicates patients with ventricular electrical instability after infarction. The induction of VF or ventricular flutter is a negative test result with no adverse long-term prognostic significance. PMID- 7863985 TI - Comparison of rest-redistribution thallium-201 imaging and reinjection after stress-redistribution for the assessment of myocardial viability in patients with left ventricular dysfunction secondary to coronary artery disease. AB - Thallium (Tl)-201 reinjection after stress-redistribution (RI) imaging has been proven to accurately identify ischemic and viable myocardium. Quantitative Tl-201 analysis after stress has also shown viable myocardium in most mild to moderate (51% to 85% of normal uptake) irreversible Tl-201 defects. However, if the main clinical question is whether a region is viable, and not whether there is inducible ischemia, a resting protocol may be more appropriate. The aim of this study was to determine whether rest-redistribution (RD) quantitative Tl-201 single-photon emission tomographic imaging provides the same information on viable myocardium as Tl-201 RI. Thus, 15 patients (mean age 58 +/- 9 years) with chronic coronary artery disease and left ventricular dysfunction (ejection fraction 35 +/- 8%) were studied by both RI and RD Tl-201 single-photon emission tomography. Regional Tl-201 uptake was assessed quantitatively using a 16-segment model. When Tl-201 images were classified as normal/reversible (viable) or irreversible (nonviable), RI showed viable myocardium in 145 of 240 myocardial regions (60%), whereas RD showed it in 103 of 240 myocardial regions (43%). The 2 imaging protocols provided concordant information in 176 of 240 myocardial regions (73%). Among the 64 (27%) discordant regions, 53 (22%) were viable by RI and nonviable by RD, whereas 11 (5%) were viable by RD and nonviable by RI (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863986 TI - Inhibitory effect of nitroglycerin and sodium nitroprusside on platelet activation across the coronary circulation in stable angina pectoris. AB - This study assessed the inhibitory effect of nitroglycerin and sodium nitroprusside on platelet aggregation in a model of platelet activation across coronary circulation. Platelet aggregation is believed to contribute to the precipitation of acute ischemic syndromes. We previously showed that rapid atrial pacing in patients with stable coronary artery disease (CAD) causes platelet hyperaggregability during blood passage in coronary circulation. Because nitroglycerin and sodium nitroprusside have been shown to inhibit platelet aggregation, we examined the effect of these drugs on this model of platelet activation. During catheterization of 19 patients with CAD (> 50% diameter narrowing of epicardial coronary arteries), we measured platelet aggregation (using whole blood platelet aggregometry) on blood samples obtained simultaneously from the coronary sinus and aorta at rest, and 2 minutes after onset of rapid atrial pacing. This procedure was repeated during an intravenous infusion of either nitroglycerin (n = 9) or sodium nitroprusside (n = 10). There was no arteriovenous difference in platelet aggregation under resting conditions. Atrial pacing caused an increase in platelet aggregation in coronary sinus blood (+64 +/- 9%; p < 0.01), but not in arterial blood (15 +/- 12% decrease; p = NS). This increase was transient and returned toward baseline 10 minutes after termination of pacing. Although resting platelet aggregation was not affected by nitroglycerin or sodium nitroprusside, activation of platelets with atrial pacing across the coronary bed was stopped by pretreatment with therapeutic doses of nitroglycerin or sodium nitroprusside. When coronary blood flow increases in patients with CAD, platelets are activated and aggregate more easily. This activation can be blunted by pretreatment with nitroglycerin or sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863987 TI - Improvement in exercise-induced left ventricular dysfunction by infusion of alpha human atrial natriuretic peptide in coronary artery disease. AB - The effects of recombinant alpha-human atrial natriuretic peptide (alpha-hANP) infusion an acute left ventricular dysfunction provoked by exercise were examined in 14 men with coronary artery disease. Patients performed symptom-limited, graded exercise on a supine bicycle ergometer. Plasma alpha-hANP and guanosine 3',5'-monophosphate (cyclic GMP) concentrations as well as hemodynamic variables were measured at rest, during and after exercise. In 14 patients whose pulmonary artery wedge pressure was > 20 mm Hg at peak exercise, the same exercise protocol was repeated at 30 minutes after starting intravenous alpha-hANP infusion (0.05 microgram.kg-1.min-1). In 8 of these patients, a Webster thermodilution catheter was advanced into the coronary sinus for measurement of coronary sinus blood flow. From the control exercise test, plasma alpha-hANP concentration increased from 86 +/- 20 pg/ml at rest to 188 +/- 32 pg/ml at peak exercise (p < 0.001), and plasma cyclic GMP concentration increased from 4.8 +/- 1.9 pmol/ml at rest to 7.2 +/- 2.9 pmol/ml at peak exercise (p < 0.001). Both plasma alpha-hANP and cyclic GMP concentrations showed a significant positive correlation with pulmonary artery wedge pressure during control exercise. With alpha-hANP infusion, systolic and diastolic pulmonary artery pressures and pulmonary artery wedge pressure were significantly decreased at all time points during exercise testing. Heart rate was increased and systolic blood pressure was significantly decreased at rest and at 3 minutes of exercise. Diastolic blood pressure, systemic vascular resistance, and pulmonary vascular resistance were significantly decreased at rest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863988 TI - Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II) AB - We randomized 151 coronary patients to placebo or pravastatin and treated them for 3 years. B-mode ultrasound quantification of carotid artery intimal-medial thickness (IMT) was obtained at baseline and sequentially during this period. The primary outcome was the change in the mean of the maximal IMT measurements across time. Effects on individual carotid artery segments (common, bifurcation, and internal carotid) and on clinical events were also investigated. Plasma concentrations of total cholesterol were lower with active treatment than with placebo (4.80 vs 6.07 mmol/L [186 vs 235 mg/dl], respectively) as were concentrations of low-density lipoprotein cholesterol (3.11 vs 4.30 mmol/L [120 vs 167 mg/dl], respectively). Plasma concentrations of high-density lipoprotein2 cholesterol were higher with active treatment (0.16 vs 0.14 mmol/L [6.1 vs 5.5 mg/dl], respectively). Active treatment resulted in a nonsignificant 12% reduction in progression of the mean-maximum IMT (from 0.068 to 0.059 mm/year) and a statistically significant 35% reduction in IMT progression in the common carotid. Active treatment was also associated with a reduction in fatal and nonfatal coronary events [corrected] (p = 0.09) and of any fatal event plus nonfatal myocardial infarction (p = 0.04). PMID- 7863989 TI - Prognostic value of the signal-averaged electrocardiogram and a prolonged QRS in ischemic and nonischemic cardiomyopathy. AB - Studies of electrocardiographic predictors of mortality in patients with chronic heart failure have reached varying conclusions. Differences in the characteristics of the patients studied may explain the conflicting results regarding both a prolonged QRS and an abnormal signal-averaged electrocardiogram (SAE). We therefore investigated the impact of the etiology of heart failure on the prognostic importance of a prolonged QRS and an abnormal SAE in 200 patients with heart failure. Patients were categorized according to etiology of heart failure and electrocardiographic parameters. The mortality of patients with a prolonged QRS was compared with mortality in those with both abnormal and normal SAEs. This was done for the entire group, and separately for those with ischemic and those with nonischemic cardiomyopathy. The mean follow-up was 18.8 months. Nonischemic patients with a prolonged QRS had significantly worse survival than other patients. However, nonischemic patients with an abnormal SAE did not have a worse prognosis than patients with a normal SAE. One-year survival of patients with a prolonged QRS was 71%, compared with 98% in patients with a normal and 87% in patients with an abnormal SAE (p < 0.05). In contrast, a prolonged QRS was not a predictor of poor prognosis in patients with ischemic cardiomyopathy (81% one year mortality). Patients with ischemic cardiomyopathy and an abnormal SAE tended to have a poorer survival than patients with a normal SAE (73% and 81% one year mortality, respectively). Thus, the etiology of heart failure affects the prognostic importance of both a prolonged QRS and an abnormal SAE. PMID- 7863990 TI - Divergent effects of chronic amiodarone administration on systolic and diastolic function in patients with heart disease. AB - The purpose of this study was to determine the effects of chronic amiodarone treatment on systolic and diastolic function in patients with cardiac disease undergoing treatment for resistant ventricular arrhythmias. Previous studies have shown that chronic amiodarone treatment either has no effect or increases left ventricular ejection fraction, but the effects on diastolic properties of the ventricle have not been defined. Twelve male patients were given loading doses of amiodarone followed by a maintenance regimen. Serial measurements of heart rate, blood pressure, and indexes of systolic and diastolic function were measured by Doppler echocardiographic techniques at baseline conditions and at 2, 8, and 12 weeks of drug therapy. Changes in altered thyroid state were excluded by serial determinations of thyroid function. Amiodarone increased left ventricular ejection fraction (+16%, p < 0.01 by 8 weeks), decreased presystolic ejection period/left ventricular ejection time (-12%, p < 0.01 by 8 weeks), and increased velocity of circumferential fiber shortening (+22%, p < 0.05 by 8 weeks). Amiodarone decreased mitral inflow velocity peak E/peak A (-7%, p < 0.01 by 12 weeks), and increased deceleration and isovolumic relaxation times incrementally (+36% [p < 0.001] and +23% [p < 0.001], respectively, at 12 weeks). Chronically administered amiodarone can improve systolic function and exert a negative lusitropic action in patients with heart disease. PMID- 7863991 TI - Antiarrhythmics Versus Implantable Defibrillators (AVID)--rationale, design, and methods. AB - The Antiarrhythmics Versus Implantable Defibrillators (AVID) study compares a strategy of initial treatment with an implantable cardioverter-defibrillator (ICD) to a strategy of initial treatment with an antiarrhythmic drug to prevent death in patients with a history of ventricular fibrillation or hemodynamically compromising ventricular tachycardia, or both. Neither arrhythmia can have been due to a transient or correctable cause. The principle exclusions are a contraindication to amiodarone therapy and inability to undergo ICD implantation. Antiarrhythmic drug therapy includes empiric amiodarone and guided sotalol. The ICDs allowed are advanced generation devices, and most are implanted transvenously. The primary end point of the study is total mortality. Secondary end points are cost and quality of life. The study was designed in 2 phases. The pilot phase enrolled 200 patients between June 1993 and June 1994. Data collected during the pilot phase confirmed that the trial is feasible. An additional 1,000 patients will be enrolled between June 1994 and March 1997. It is anticipated that all 1,200 patients will be followed until September 1998, and will be included in the intention-to-treat analysis. PMID- 7863992 TI - Syncope associated with exercise, a manifestation of neurally mediated syncope. AB - A retrospective review of patients evaluated at a university-based referral hospital was performed to assess the basis for syncope associated with exercise in young patients. Over an 8-year period, 54 consecutive young patients (aged 12 to 30 years) were referred for evaluation of frank syncope. Twelve patients had syncope associated with exercise (group I) and 42 patients had syncope not associated with exercise (group II). Patients underwent physical examination, chest x-ray, 2-dimensional echocardiography, and in selected cases, cardiac catheterization. Head-up tilt-table testing was performed in 11 of 12 group I patients. Ten group I patients had no evidence of structural heart disease: 9 of these 10 (90%) developed syncope with tilt-table testing. Head-up tilt-table testing was performed in 41 of 42 group II patients: 34 (83%) developed syncope with tilt-table testing. Standard cardiac electrophysiologic study was performed in 9 of 12 group I and in 30 of 42 group II patients, and identified a basis for syncope in only 2 group I and 1 group II patients. Among 9 group I patients with a positive result on head-up tilt-table testing and no evidence of structural heart disease (mean follow-up 4.3 years), 7 are without further episodes of syncope; 3 have discontinued medication and 5 have resumed at least limited exercise. In conclusion, susceptibility to tilt-induced syncope was the most frequent finding in young patients without structural heart disease referred for evaluation of exercise-associated syncope. Tilt-table testing may be an important diagnostic tool for the evaluation of these patients. PMID- 7863993 TI - Effects of atenolol on rest and exercise hemodynamics in patients with mitral stenosis. AB - Beta-blocker therapy remains controversial in patients with mitral stenosis. In this randomized, double-blind, crossover, placebo-controlled study, the effects of atenolol (50 and 100 mg/day) were assessed in 15 patients (aged 46 +/- 11 years) with mitral stenosis (mean valve area 1.0 +/- 0.4 cm2; New York Heart Association class II or III) at rest and during upright bicycle ergometry. Doppler echocardiography was used to compare heart rate, cardiac and stroke volume indexes, diastolic filling period, and peak and mean transmitral gradients; a metabolic cart was used to obtain maximal oxygen consumption, carbon dioxide production, and anaerobic threshold. Beta-blocking therapy did not improve exercise time, external work, maximal oxygen consumption rate, or anaerobic threshold. Compared with placebo, maximal oxygen consumption rate and cardiac index decreased (p < 0.05) > 11% and > 20%, respectively, with atenolol at peak exercise. Although heart rate was reduced > 20% and diastolic filling period prolonged > 40% by atenolol at rest and exercise (p < 0.05), stroke volume index changed little compared with placebo. The data suggest that despite lower transvalvular pressure gradients, little benefit in exercise performance is achieved with beta-blocker therapy in patients with severe mitral stenosis. PMID- 7863994 TI - Predictors of outcome of tricuspid valve replacement in carcinoid heart disease. AB - The cardiac valvular surgical experience of patients in the Duke Carcinoid Database was reviewed to assess operative outcome. Of the 604 patients in the database, 19 patients with carcinoid heart disease were identified by cardiac catheterization or echocardiography, or both. Eight of these underwent tricuspid valve replacement surgery with bioprostheses (2 also had open pulmonic valvuloplasty). Compared with patients medically managed, surgically treated patients were similar with the exception that they had higher right atrial mean (17 +/- 6 vs 9 +/- 4 mm Hg, p = 0.03) and v-wave (27 +/- 6 vs 17 +/- 7 mm Hg, p = 0.04) pressures. Of the 8 surgical patients, 5 (63%) died within 30 days. Causes of death included tricuspid valve thrombosis, cerebral vascular accident, coagulopathy, renal failure, and intractable right heart failure. High comorbidity was present in all 8 patients. There was a weak trend (p = 0.17) toward lower Charlson comorbidity indexes in survivors (6.7 +/- 0.6) compared with nonsurvivors (7.6 +/- 0.9). Age was significantly lower (p = 0.036) in survivors (46 +/- 13 years) compared with nonsurvivors (69 +/- 4 years). Extended follow-up revealed 2 patients who survived beyond a decade. Review of 47 carcinoid valve replacement cases (Duke Carcinoid Database and 39 published cases) revealed a 30-day mortality of 56% for patients > 60 years of age, and 0% for those < or = 60 years of age (p < 0.0001). Although valve replacement surgery can afford prolonged palliation from carcinoid heart disease, it is associated with a significant mortality risk. Careful preoperative risk stratification by age and comorbidity may provide a means for optimal selection of surgical candidates. PMID- 7863995 TI - Additional value of biplane transesophageal echocardiography in assessing the genesis of mitral regurgitation and the feasibility of valve repair. AB - To determine the additional diagnostic value of biplane transesophageal echocardiography (TEE) in patients undergoing mitral valve surgery, we studied 48 patients with severe mitral regurgitation. Transesophageal echocardiographic video recordings were reorganized in separate transverse and longitudinal sections to allow independent evaluation. Mechanism of mitral regurgitation and anatomic abnormalities of the mitral valve were assessed by all 3 transesophageal echocardiographic modalities and were related to surgical findings. Biplane TEE detected increased leaflet mobility with a sensitivity of 91% and a specificity of 84%, and restricted leaflet mobility with a sensitivity of 100% and a specificity of 97%. Biplane TEE was accurate in the diagnosis of most of the anatomic abnormalities associated with these mechanisms. However, the sensitivity for detecting subvalvular abnormalities (including papillary muscle abnormalities) was poor, and measurement of the annular diameter had a poor correlation with annular dilatation. Although the yield of biplane TEE was better than either transverse or longitudinal TEE alone, the differences did not reach statistical significance, because of the size of the patient group. The surgical procedure (either valve repair or replacement) was correctly predicted with transverse TEE in 71%, with longitudinal TEE in 69%, and with biplane TEE in 79% of the patients. All 3 transesophageal echocardiographic modalities are very capable of assessing the anatomic abnormalities and mechanism of mitral regurgitation, as well as predicting the feasibility of valve repair. PMID- 7863996 TI - Prognostic significance of spectral turbulence analysis of the signal-averaged electrocardiogram in patients with idiopathic dilated cardiomyopathy. AB - The aim of this study was to assess whether spectral turbulence analysis (STA) of the signal-averaged electrocardiogram (SAECG) is of prognostic use in patients with idiopathic dilated cardiomyopathy. SAECGs were recorded at presentation in 84 patients with idiopathic dilated cardiomyopathy and STA was performed using 183 Del Mar software. STA was abnormal (> or = 3 of the 4 standard parameters beyond the normal range) in 31 patients (37%). Patients were followed for a mean duration of 24 +/- 18 months (range 1 to 59) during which time 24 (29%) developed progressive heart failure (14 underwent cardiac transplantation), 4 died suddenly or had aborted sudden death, and the others remained clinically stable. Progressive heart failure occurred more often in patients who had an abnormal versus a normal STA result (15 [48%] vs 9 [17%]; p < 0.002). Actuarial survival revealed a 1-year survival of 90% in patients with a normal STA result, and 63% in patients with an abnormal STA result (p < 0.01). The predictive ability of STA to identify patients with progressive heart failure was sensitivity 63%, specificity 77%, positive predictive value 54%, and negative predictive value 83%. Univariate analysis identified peak oxygen consumption as having the largest relative risk for the development of progressive heart failure (9.55, 95% confidence interval [CI] 2.1 to 43.9). Left ventricular end-diastolic dimension (relative risk 4.18, 95% CI 1.5 to 11.4) and STA (relative risk 3.81, 95% CI 1.7 to 8.8) were also significantly associated with the development of progressive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7863997 TI - Which definition for echocardiographic left ventricular hypertrophy? AB - Left ventricular (LV) hypertrophy is diagnosed on the basis of LV mass measurement at echocardiography. However, various thresholds for defining LV hypertrophy have been published, ranging from 111 to 134 g/m2 and from 100 to 125 g/m2 in men and women, respectively. The aim of our study was to evaluate variations in the prevalence of LV hypertrophy induced by the application of different threshold values among hypertensive subjects. LV mass was calculated in 349 hypertensive patients from an M-mode LV tracing obtained by left parasternal view in 83% and by subcostal view in 17% of patients. The prevalence of LV hypertrophy ranged from 17% to 39%, according to the threshold value applied (from 10% to 47%, and from 19% to 39% in women and men, respectively). As expected, the prevalence of LV hypertrophy in obese patients of both sexes was higher when applying the usual height-indexed threshold (143 and 102 g/m for men and women, respectively) than when applying the usual body surface area-indexed threshold (134 and 110 g/m2 for men and women, respectively). The use of normalized thresholds when comparing different indexation methods (in this case, 145 g/m for men, 120 g/m for women) will minimize these variations in part due to the threshold choice. Considering the clinical and therapeutic implications associated with the presence of LV hypertrophy, better standardization of definitions is needed; this could be based either on better-designed cooperative normality studies or meta-analysis of risk stratification. PMID- 7863998 TI - Coronary vasoconstriction induced by mental stress (simulated public speaking). PMID- 7863999 TI - T-wave normalization during dobutamine echocardiography for diagnosis of viable myocardium. PMID- 7864000 TI - Usefulness of U-wave analysis in detecting significant narrowing limited to a single coronary artery. PMID- 7864001 TI - Attitudes of attending physicians to the incidental diagnosis of hypercholesterolemia in hospitalized patients. PMID- 7864002 TI - Impairment of driving abilities in patients with supraventricular tachycardias. PMID- 7864003 TI - Reappraisal of the vasodepressor reflex in carotid sinus syndrome. PMID- 7864004 TI - Adenosine therapy for supraventricular tachycardia during pregnancy. PMID- 7864005 TI - Transient loss of complete bundle branch block patterns during exercise. PMID- 7864006 TI - Left ventricular systolic dysfunction diastolic filling characteristics and exercise cardiac reserve in mitral stenosis. PMID- 7864007 TI - Comparison between cine magnetic resonance velocity mapping and first-pass radionuclide angiocardiography for quantitating intracardiac shunts. PMID- 7864008 TI - Use of echocardiography for detecting aortic valve leaflet avulsion and predicting repair potential after balloon valvuloplasty. PMID- 7864009 TI - Safety of dipyridamole testing in patients with cerebrovascular disease. PMID- 7864010 TI - The missing second: what is the correct unit for the Bazett corrected QT interval? PMID- 7864011 TI - The evolving utility of intracoronary ultrasound. PMID- 7864012 TI - Range of normal valve annulus size in neonates. PMID- 7864013 TI - Optimal size of self-adhesive preapplied electrode pads in pediatric defibrillation. PMID- 7864014 TI - Effects of short-term brachial arterial vasodilator infusions on forearm blood flow response to acetylcholine. PMID- 7864015 TI - Use of transesophageal atrial pacing with adenosine infusion to evaluate ventricular preexcitation. PMID- 7864016 TI - A response to the letter on electrical cardioversion resulting in death from synchronization failure. PMID- 7864017 TI - Electrical cardioversion resulting in death from synchronization failure. PMID- 7864018 TI - Complications of cardioversion. PMID- 7864019 TI - Benefits of implantable defibrillator therapy. PMID- 7864020 TI - Multivessel angioplasty. PMID- 7864021 TI - Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastics reveals extensive apoptosis as the probable basis for ineffective hematopoiesis. AB - Despite hypercellular bone marrows (BM), peripheral cytopenias are the rule in patients with myelodysplastic syndromes (MDS). This study examined the roles played by cell birth and cell death rates in generating this paradox. Cell kinetics from BM biopsies of 35 MDS patients were measured using intravenous infusions of either iododeoxyuridine or bromodeoxyuridine, or both. Degree of apoptosis or programmed cell death (PCD) was estimated using in situ end-labeling of DNA directly from BM biopsies, which were simultaneously double-labeled from proliferation/PCD. MDS were found to be highly proliferative disorders with large numbers of myeloid, erythroid, and megakaryocytic cells synthesizing DNA. Median cycling time (Tc) of myeloblasts was more rapid than that of patients with acute myeloid leukemia (44.1 hr vs. 56.0 hr). Interestingly, most marrow cells of all three lineages in 32 of 34 evaluable cases were undergoing PCD. In 19 of 32 patients, greater than 75% cells were apoptotic. Surprisingly, large numbers of S phase cells were found to be simultaneously undergoing PCD, as were stromal cells of the BM microenvironment. We conclude that the extensive apoptosis in hematopoietic cells effectively cancels the high birth rate resulting in ineffective hematopoiesis and accounting for deficient bone marrow function. PMID- 7864022 TI - Abnormal platelet von Willebrand factor (vWF) as a marker of abnormal function in megakaryocytic dysplasia. AB - The myelodysplastic syndromes (MDS) are neoplastic disorders of the hemopoietic system; multilineage involvement is also evidenced by specific cellular dysfunctions. The von Willebrand factor (vWF), synthesized and processed in the megakaryocytes (MK), is stored in the alpha granules of the platelets. The platelet vWF multimeric pattern was studied in 18 patients with MDS, and in 4 with pernicious anemia (PA), to investigate whether the processing of vWF is abnormal in the megakaryocytic dysplasia. An abnormal multimeric pattern was observed in 10/18 MDS and 4/4 PA patients. The abnormality of this specific protein is the discrete expression of the basic disorder, and is reversible when hemopoiesis is normalized. Although the data do not allow any conclusion, abnormal synthesis is the likely explantation of the abnormality. PMID- 7864023 TI - Initiation codon mutation (ATG --> ATA) of the beta-globin gene causing beta thalassemia in a Swedish family. AB - An initiation codon mutation ATG-->ATA of the beta-globin gene was found in seven members of three generations of a family living in northern Sweden. This mutation, which has not previously been described, changes the initiation codon for methionine into a codon for isoleucine and will then result in a beta zero thalassemic phenotype. The affected family members all present hematological findings typical for beta-thalassemic trait, with slight anemia, marked microcytosis, and increased levels of Hb A2. PMID- 7864024 TI - Alpha-2a interferon therapy and antibody formation in patients with essential thrombocythemia and polycythemia vera with thrombocytosis. AB - In ten patients with essential thrombocythemia and polycythemia vera with thrombocytosis we have investigated the therapeutic effect of recombinant alpha 2a interferon (Roceron-A) given subcutaneously in a maintenance dosage of 3 million units three times weekly. The aim was to normalize the platelet count (< or = 400 x 10(9)/L). One of the secondary aims was to study platelet activity measured as beta-thromboglobulin (beta-TG) in urine. All but one patient could administer the injections and in all patients a significant reduction in platelet values was seen. The treatment was discontinued in three patients due to side effects of interferon, two because of hair loss (one with irreversible alopecia), and one because of depression. Three patients developed antibodies to alpha-2a interferon and a concomitant rise in the platelet level; in one patient therapy was switched to leukocyte alpha-interferon with an excellent response. The initial levels of beta-TG were elevated in 9/10 patients and were significantly reduced at 6 months in 4/5 patients not developing antibodies. Six patients are still on alpha-interferon therapy with a long-term follow-up of 3-3.5 years. We conclude that alpha-interferon therapy may be an alternative in patients with thrombocytosis and/or complications necessitating treatment. PMID- 7864025 TI - Fibrinogen/fibrin degradation products and D-dimer in clinical practice: interpretation of discrepant results. AB - In clinical practice, occasionally some patients show dissociated values of fibrinogen/fibrin degradation products (FDP) and D-dimer (cross-linked fibrin degradation products). In an attempt to assess the frequency, clinical backgrounds, and hemostatic states of these cases, FDP and D-dimer were simultaneously measured together with other hemostatic parameters in 371 samples from patients with various diseases. As a whole, FDP were elevated in parallel with the progress of activation of blood coagulation and fibrinolysis. However, in patients with elevated FDP and/or D-dimer, 11.5% of samples showed relatively lower D-dimer values than those expected from FDP levels, and these were regarded as an apparently dissociated group. In the dissociated group, activation of coagulation and fibrinolysis occurred to a lesser extent than others. Analysis of these samples suggested that the possible reasons for the dissociation between FDP and D-dimer values were accelerated fibrinogenolysis with or without secondary fibrinolysis, accelerated fibrinogenolysis by non-plasmic proteinases, elevated soluble fibrin, and possibly false-positive FDP levels due to unclottable fibrinogen remaining in the serum samples. In practice, simultaneous measurements of FDP and D-dimer are useful for more accurate estimation of hyperfibrinolytic states. PMID- 7864026 TI - Significant and persistent improvement of thrombocytopenia after splenectomy in an adult with the Wiskott-Aldrich Syndrome and intra-cerebral bleeding. AB - The Wiskott-Aldrich syndrome is an X-linked inherited immunodeficiency disorder characterized by thrombocytopenia, recurrent infections and eczema. Its best management option is HLA-identical bone marrow transplantation; when this is not feasible, splenectomy, followed by continuous prophylactic antibiotics, represents the alternative of choice. The present case report relates the excellent outcome of an adult with the Wiskott-Aldrich syndrome who suffered his first major complication of the disease at age 33 years, an intracerebral hemorrhage. Since an uneventfull splenectomy, thrombocytopenia has significantly improved, and he has remained free of infections for a follow-up period of 3 years while being treated with prophylactic antibiotics. PMID- 7864027 TI - A new myeloproliferative syndrome. AB - We report here two cases of a previously undescribed myeloproliferative disorder. Both were young adult males who presented with generalized lymphadenopathy, splenomegaly, leukocytosis, polycythemia, and persistent thrombocytopenia. The leukocyte alkaline phosphatase (LAP) score was low in both cases, and the bone marrow was hypercellular without dysplasia or fibrosis, but lacked the Philadelphia chromosome, BCR gene rearrangement, or other karyotypic abnormalities. The clinical course was indolent in each case. One patient died from an unusual "blast crisis" after 12 years, while the second patient remains in a complete hematologic remission on hydroxyurea and alpha interferon 4 years from diagnosis. Interestingly, changes in therapy in this patient have consistently resulted in precise and concerted fluctuations in his blood counts, with the red and white cells cycling together and the platelets and mean corpuscular volume (MCV) changing concomitantly but in the opposite direction. This unique myeloproliferative disorder is distinguishable from all previously described forms of chronic myeloid leukemia and other myeloproliferative syndromes. PMID- 7864028 TI - Morphological, ultrastructural, and genetic characterization of an unusual T-cell lymphoma in a patient with sinus histiocytosis with massive lymphadenopathy. AB - Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare benign disease of unknown etiology. It is rarely associated with malignant lymphoma. This report documents the first case of a T-cell lymphoma, which developed in a patient with a 10-year history of SHML. The disease was complicated by hypereosinophilia and massive retroperitoneal lymphadenopathy. Histological examination of a cervical lymph node biopsy during the terminal phase identified a lymphoma composed of cells with morphological plasmacytoid features. Ultrastructurally, the tumor cells showed poorly developed cytoplasm, nuclei with peripheral chromatin clumping, and inconspicuous nucleoli. Cytogenetic studies showed two related clones. On immunohistochemical staining tumor cells were positive with monoclonal antibodies (mAb) CD3 and CD45RO. Southern blotting analysis identified clonal rearrangements in the T-cell receptor (TCR) alpha, beta and gamma genes. Thus, T cell lineage of the tumor cells was established. In situ hybridization of interleukin-2 (IL-2) and interleukin-5 (IL-5) cDNA probes on tissue sections identified the synthesis of IL-5 by the eosinophils, suggesting an autocrine pathway of eosinophilopoiesis leading to hypereosinophilia in this patient. PMID- 7864029 TI - Increase of thrombopoiesis by M-CSF in a patient with aplastic anemia. PMID- 7864030 TI - Primitive neuroectodermal tumor following successful treatment of Hodgkin's disease. PMID- 7864031 TI - Plasma protein Z levels in healthy newborn infants. PMID- 7864032 TI - Recurrent "retinoic acid syndrome" during induction of remission in acute promyelocytic leukemia. PMID- 7864033 TI - Therapeutic efficacy of Ambisome: A cautionary note. PMID- 7864034 TI - Spurious leukocytosis-simulating relapse of chronic myeloid leukemia after bone marrow transplant: possible relationship to hypercholesterolemia and hyperbilirubinemia. PMID- 7864035 TI - Response to "Treatment of childhood chronic ITP". PMID- 7864036 TI - Treatment of acute promyelocytic leukemia with all-trans retinoic acid during the third trimester of pregnancy. PMID- 7864037 TI - Acute pancreatitis associated with interferon-alpha therapy for chronic myelogenous leukemia. PMID- 7864038 TI - Chorionic villi sampling: laboratory experience with 4,000 consecutive cases. AB - Experience with 4,000 consecutive CVS cases shows that 1) the combination of both the direct and culture methods greatly reduces false diagnoses and maternal cell contamination; 2) the time interval between the sampling procedure and processing of villus specimens influences the quality of direct preparations; 3) maternal cell contamination (MCC) can be minimized with dissection of CVS specimens. We have compiled a large volume of confined placental mosaicism (CPM) cases to serve as a resource in interpreting mosaic cytogenetic findings. It was noted that, in up to 92% of the mosaic cases, the abnormal cell line was confined to the placenta. The frequency of true chromosomal mosaicism was 0.2%, and is not different from that for amniocentesis. PMID- 7864039 TI - Aplasia cutis congenita with epibulbar dermoids: further evidence for syndromic identity of the ocular ectodermal syndrome. AB - We have investigated 2 young South African girls with aplasia cutis congenita, epibulbar dermoids, and strabismus. This unique association of anomalies was first documented in two unrelated boys by Toriello et al. [1993: Am. J. Med. Genet. 45:764-766]. Our clinical and histological findings are markedly similar, and we think this to be the second report of individuals with this rare syndrome. PMID- 7864040 TI - Deletion of (11)(q24.2) in a mother and daughter with similar phenotypes. AB - A del(11) (q24.2) was ascertained in a 2-year-old child and subsequently in her 20-year-old mother. Both mother and daughter had developmental delay, short stature, and "coarse" facial appearance. We compare our patients' manifestations to those associated with the distal 11q2 deletion phenotype ("Jacobsen" syndrome), and to the one other reported case of del(11)(q24.2). Our patients did not resemble this latter case, but had some findings in common with Jacobsen syndrome. We present our findings in order to contribute to the information on 11q2 deletions. PMID- 7864041 TI - Neurofibromatosis type I (NFI) in Israeli families: linkage analysis as a diagnostic tool. AB - Linkage analysis of 18 neurofibromatosis type I (NFI) families was performed using intragenic and flanking polymorphic markers. The aims of the analysis were prenatal diagnosis of at-risk fetuses, and of asymptomatic individuals who were relatives of NFI patients. Prenatal diagnosis was performed in 9 pregnancies of 7 families; 5 fetuses were diagnosed as affected. In 6 families with an affected spouse, the request was to identify informative polymorphisms to be used in future pregnancies. Presymptomatic diagnosis was performed in 4 families. One individual, a brother of an NFI patient, was found to have Lisch nodules as the only NFI symptom. Linkage analysis indicated that if this person is a carrier of the NFI gene, he must be a product of intragenic crossover. In 2 individuals with a new NFI mutation, the origin of the NFI-bearing chromosomes was paternal. The same observation was noted by others. A summary of published cases shows that some 90% of the NFI-bearing chromosomes of patients with new mutations were of paternal origin. We therefore suggest that for the purpose of prenatal diagnosis in carriers of NFI new (and unidentified) mutations, the paternal chromosome will be considered as the NFI-bearing chromosome. PMID- 7864042 TI - Social-emotional and behavioral adjustment in children with Williams-Beuren syndrome. AB - In children with Williams-Beuren syndrome (WBS), disturbed behaviors (neurotic, antisocial, and hyperactive) [Arnold et al., 1985: Dev Med Child Neurol 27:49-59; Udwin et al., 1987: J Child Psychol Psychiat 28:297-309] have been described. To study the behavior disturbances and social-emotional adjustment in children with WBS, a group of N = 19 patients was compared with a control group, matched for age, gender, and nonverbal reasoning abilities. Parents were asked to assess the children's behavior in terms of a list of 20 items of the Child Behavior Checklist (CBCL) [Achenbach and Edelbrock, 1983: Manual for the Child Behavior Checklist] and the Vineland Social Maturity Scale (VSMS) [Luer et al., 1972: Kurzform der Vineland Social Maturity Scale]. As compared with the control group, children with WBS differ significantly in their social behavior towards strangers. They exhibit no reserve or distancing behavior and would, for instance, follow a stranger without hesitation. They are described as showing a hypersensitivity to sounds that is more pronounced than in the control group. Finally, they are found to be significantly less well-adjusted socially than the control individuals. PMID- 7864043 TI - Ascertainment models incorporating effects of variable age of onset. AB - In pedigree analysis, nonrandom sampling, or ascertainment through affected persons, occurs commonly, making it necessary to adjust appropriately for the ascertainment procedure in order to secure the correct interpretation of results from genetic analysis. Ascertainment models for dichotomous phenotypes are considered for disorders characterized by variable age of onset, particularly considering those instances where the probability of ascertainment may be influenced by the age of onset of the disorder. For a variety of theoretical and practical reasons, sigmoidal functions appear to be well suited to the modeling of occurrence of a binary event, such as proband status. Relevant ascertainment models incorporating a modified exponential ascertainment function having such a sigmoidal form are described, together with associated modifications to the likelihood for the ascertained pedigree. Alternative parameterizations and methods for obtaining initial estimates are also discussed. PMID- 7864044 TI - Autosomal dominant (Beukes) premature degenerative osteoarthropathy of the hip joint unlinked to COL2A1. AB - Molecular investigations have been undertaken in several separate large South African families with autosomal dominant skeletal dysplasias in which premature degenerative osteoarthropathy of the hip joint was the major manifestation. There are sometimes additional minor changes in the spine and these conditions fall into the general spondyloepiphyseal dysplasia (SED) nosological category. In some kindreds, linkage between phenotype and the type II collagen gene (COL2A1) has been established, while in others there is no linkage. We have now completed molecular linkage investigations in an Afrikaner family named Beukes, in which 47 members in 6 generations have premature osteoarthropathy of the hip joint. A LOD score of minus infinity indicates that this condition is not the result of a defect of the COL2A1 gene. PMID- 7864045 TI - Submicroscopic deletion of chromosome region 16p13.3 in a Japanese patient with Rubinstein-Taybi syndrome. AB - In a series of 25 Japanese patients with Rubinstein-Taybi syndrome, we screened, by high-resolution GTG banding and fluorescence in situ hybridization of a cosmid probe (RT1, D16S237), for microdeletions associated with this syndrome. In one patient, a microdeletion was demonstrated by in situ hybridization, but none were detected by high-resolution banding. PMID- 7864046 TI - Potential use of buccal smears for rapid diagnosis of autosomal trisomy or chromosomal sex in newborn infants using DNA probes. AB - Buccal smears from 3 women and 1 man were probed with alpha satellite DNA probes for chromosomes 8, 18, X, and Y. Buccal smears were also collected from an adolescent phenotypic female with uterine agenesis, as well as from newborn infants with suspected trisomy 18 and trisomy 21. The clinical cases were confirmed with conventional cytogenetic studies of peripheral lymphocytes. Overall probe efficiency at detecting expected chromosome number in interphase cells was found to be 71% +/- 6.8%. Higher than expected n-1 signal numbers may be due to karyopyknotic intermediate epithelial cells present in all collected samples. Overall probe efficiency was found to be consistent using alpha satellite and cosmid probes, both of which accurately reflected the modal copy number of the target chromosomes. False trisomy was less than 1%. This study suggests DNA probes can be used in buccal smears for rapid diagnosis of trisomies and chromosomal sex in newborns, but because of high rates of false hypoploid signals, probed buccal smear specimens may not be accurate at diagnosing mosaicism. PMID- 7864047 TI - Molecular analysis of 53 fragile X families with the probe StB12.3. AB - Fifty-three pedigrees with the fragile X syndrome have been studied for amplification of the CGG repeat sequence adjacent to the CpG island in the FMR1 gene. Probe StB12.3 allowed direct detection of affected males, carrier females, normal transmitting males, as well as prenatal diagnosis. Comparison of our molecular data with our previous linkage data from 38 families indicates the effectiveness of direct DNA analysis. A total of 325 individuals were studied and no new mutation was found. All daughters of males with a premutation had a premutation. When the mother had a full mutation no children had a premutation. In premutated mothers, the size of the premutation seems to be a determining factor for the transition to the full mutation. All affected males had a full mutation or mosaicism and only 42% of the females with a full mutation were mentally impaired. Analysis of large families over 3 generations illustrated clearly the Sherman paradox. Furthermore, the analysis of these families is in reasonable agreement with the multiallelic model of Morton and Macpherson [Proc Natl Acad Sci USA 89:4215-4217, 1992]. Mosaic cases in the offspring of the mothers with a full mutation suggest a maternal germinal mosaicism. Then an abnormal methylation and a somatic heterogeneity established in very early steps of embryogenesis could explain these cases. PMID- 7864048 TI - Schinzel-Giedion syndrome: autopsy report and additional clinical manifestations. AB - Schinzel-Giedion syndrome (SGS) is a rare and incompletely defined condition. This is the third postmortem study on a boy with SGS and other unusual findings. He had a primitive neuroectodermal tumor in the lumbosacral region, bilateral syndactyly of hands and feet, and brain anomalies in addition to the major manifestations of the syndrome. We consider these clinical findings as possible additional manifestations of the syndrome since, of 19 SGS patients reported, 4 had syndactyly and 3 had embryonal tumors. In addition, the 3 published necropsy studies report brain anomalies. Knowledge that these changes occur in SGS may help facilitate diagnosis and improve our understanding of the syndrome. PMID- 7864049 TI - Oculo-ectodermal syndrome: a new case. AB - We report on a girl with aplasia cutis congenita, epibulbar dermoids, and macrocephaly. To our opinion she has the same ocular-ectodermal syndrome as described by Toriello et al. [Am J Med Genet 45: 764-766, 1993]. PMID- 7864050 TI - Fragile X syndrome: diagnostic and carrier testing. Working Group of the Genetic Screening Subcommittee of the Clinical Practice Committee. American College of Medical Genetics. PMID- 7864051 TI - Fragile X screening: what is the real issue? PMID- 7864052 TI - Troyer Syndrome: report of the first "non-Amish" sibship and review. PMID- 7864053 TI - Congenital heart defect in a patient with the Hallermann-Streiff syndrome. PMID- 7864054 TI - Re: "Acrorenal syndrome in a child with renal failure" [Akl, 1994]. PMID- 7864055 TI - Ectrodactyly in trisomy 13 syndrome. PMID- 7864056 TI - Nosology of the syndrome of spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy. PMID- 7864057 TI - Double fingernails on fifth fingers. PMID- 7864058 TI - The critical region for Angelman syndrome lies between D15S122 and D15S113. PMID- 7864059 TI - Frequency and chronological distribution of dental enamel hypoplasia in enslaved African Americans: a test of the weaning hypothesis. AB - The dentition of 27 enslaved African Americans from archaeological sites in Maryland and Virginia were examined. All 17 males and 7 of the 10 females in this study exhibited enamel hypoplastic defects indicative of systemic nutritional and disease stresses interfering with amelogenesis. Estimates of the ages of occurrence of these defects show that most occur between 1.5 and 4.5 years of age, 0.5-3.75 years later than historically documented weaning age (9-12 months of age) in similar plantation populations. Comparisons are made with studies of dental enamel hypoplasia in contemporaneous enslaved and free African American populations, including our data on 75 individuals from the First African Baptist Church cemetery in Philadelphia. These populations were highly stressed. While there appears to be a modest effect of early weaning stress, no direct relationship of peak frequencies to weaning age can be shown. These data raise questions about the attribution of peak hypoplasia frequencies to age at weaning or "post-weaning" stresses in previous paleopathological studies. High hypoplasia frequencies during the middle years of enamel development are more likely the result of a combination of 1) multiple environmental stresses, 2) differences in hypoplastic susceptibility in enamel, and 3) random factors. PMID- 7864060 TI - Detecting clinical and balanced selection using spatial autocorrelation analysis under kin-structured migration. AB - Recently spatial autocorrelation has been employed to infer microevolutionary processes from patterns of genetic variation. In theory, different processes should show characteristic signature correlograms; e.g., clinal selection should produce correlograms decreasing from positive to negative autocorrelation, whereas uniform balanced selection should lead to no spatial autocorrelation. The ability of a statistical method such as spatial autocorrelation analysis to distinguish between these selective regimes or even to detect departures from neutrality is dependent on the strength of the evolutionary force and the population structure. Weak selection or migration will not be apparent against the expected background of stochastic noise. Moreover, the population structure may generate sufficient stochastic variation such that even strong evolutionary forces may fail to be detected. This study uses computer simulation to examine the effects of kin-structured migration and three different selective regimes on the shape of spatial correlograms to assess the ability of this technique to detect different microevolutionary processes. Genetic variation among 8 loci is simulated in a linear set of 25 artificial populations. Kin-structured stepping stone migration among adjacent populations is modeled; directional, balanced, and clinal selection, as well as neutral loci are considered. These experiments show that strong selection produces correlograms of the predicted shape. However, with an anthropologically reasonable population structure, considerable stochastic variation among correlograms for different alleles may still exist. This suggests the need for caution in inferring genetic process from spatial patterns. PMID- 7864061 TI - Social implications of gummivory in marmosets. AB - Gummivory or exudate feeding is a major dietary specialization which has received relatively little attention in the literature. While plant exudates contribute to the diet of many primate species, we suggest that the callitrichid species Cebuella pygmaea and Callithrix jacchus are obligate exudate feeders under free ranging conditions. Callithrix jacchus provides an excellent model for examining the effects of exudate feeding and foraging upon social behavior, since other callitrichid species of similar body size do not share this dietary specialization. We review the effects of exudate foraging on specific social behaviors observed both in field and laboratory populations of C. jacchus. By comparing this species to closely related species, exudate foraging is seen to (1) be retained under laboratory conditions, (2) increase the frequency of territorial marking behavior while decreasing the frequency of overt aggression in males, (3) decrease the duration of infant care, and (4) increase the number of nonadults in social groups but not affect group size. The evidence presented supports the hypothesis that the consequences of exudate foraging in C. jacchus are fundamental and socially complex. PMID- 7864062 TI - Cranial variables as predictors of hominine body mass. AB - Body mass is a key variable in investigating the evolutionary biology of the hominines (Australopithecus, Paranthropus, and Homo). It is not only closely related to life-history parameters but also provides a necessary baseline for studies of encephalization or megadonty. Body mass estimates are normally based on the postcranial skeleton. However, the majority of hominid fossils are cranio dental remains that are unassociated with post-cranial material. Only rarely can postcranial material be linked with cranio-dentally defined hominid taxa. This study responds to this problem by evaluating body mass estimates based on 15 cranial variables to determine whether they compare in reliability with estimates determined from postcranial variables. Results establish that some cranial variables, and particularly orbital area, orbital height, and biporionic breadth, are nearly as good mass predictors for hominoids as are some of the best postcranial predictors. For the hominines in particular, orbital height is the cranial variable which produces body mass estimates that are most in line with postcranially generated estimates. Both orbital area and biporionic breadth scale differently in the hominines than they do in the other hominoids. This difference in scaling results in unusually large estimates of body mass based on these variables for the larger-sized hominines, although the three cranial variables produce equivalent predicted masses for the smaller-bodied hominines. PMID- 7864063 TI - Further evidence of lead contamination of Omaha skeletons. AB - A previous analysis of Omaha skeletons dating between A.D. 1780 and 1820 revealed the presence of lead in all skeletons with high concentrations in children and adult males (Reinhard and Ghazi [1992] Am. J. Phys. Anthropol. 89:183-195). Two likely explanations for the high lead levels were presented: 1) metabolic absorption of lead and 2) diagenetic uptake of lead by the bones from postmortem application of pigments to the corpse. Two types of lead were available to the Omaha tribe: 1) Mississippi Valley type, and 2) non-Mississippi Valley type. It has been suggested that red-lead pigment mixed with mercury sulphide (cinnabar) applied to the corpse may have been one of the sources of lead found in bones. Further isotopic analyses of samples of pigment and metallic lead artifacts associated with the skeletons revealed that non-Mississippi Valley type lead is present in the pigment while Mississippi Valley type lead comes from metallic artifacts. Both lead and mercury were found in the pigment samples, verifying that a lead-based pigment mixed with cinnabar-based pigment was used as a cosmetic by the Omaha. Isotopic analysis of lead in skeletons indicates that the pigment contributed most to lead content of bone. This new evidence clarifies the previous study and suggests specific mechanisms by which lead became incorporated into bone. PMID- 7864064 TI - A re-evaluation of subspecific variation and canine dimorphism in woolly spider monkeys (Brachyteles arachnoides). AB - A recent study suggests that differing populations of woolly spider monkeys exhibit a substantial degree of morphological, cytogenetic, and behavioral variation. We re-evaluate the differences between populations in the degree of canine tooth height sexual dimorphism and in the frequency of thumbs. Statistical analysis of variation in the degree of canine sexual dimorphism between these populations fails to provide strong evidence for subspecific variation: differences in the degree of canine dimorphism cannot be considered statistically significant. Differences between populations in the frequency of thumbs are, however, statistically significant. The lack of clear distinctions between populations in the degree of canine dimorphism complicates assessments of behavioral variation between these populations. We suggest that the level of geographic variation in woolly spider monkey canine dimorphism is not consistent with subspecific status. PMID- 7864065 TI - Functional tongues and neanderthal vocal tract reconstruction: a reply to Dr. Houghton (1993). PMID- 7864066 TI - American Association of Physical Anthropologists. Membership list. PMID- 7864067 TI - Hormonal regulation, pharmacology, and membrane sorting of vertebrate Na+/H+ exchanger isoforms. AB - Since the cloning of the first member of the Na+/H+ exchanger (NHE) family, termed NHE1, four NHE isoforms have been cloned (NHE2, NHE3, NHE4, and the trout beta-NHE) and expressed in exchanger-deficient cell lines. All these isoforms exhibit significant identity to NHE1 and possess a similar hydropathy profile with two highly conserved transmembrane segments presumably involved in ion transport. These isoforms are allosterically activated by intracellular H+, regulate intracellular pH in a Na(+)-dependent manner, and are inhibited by amiloride and 5-amino derivatives with distinct Ki values. NHE1 is the amiloride sensitive, growth factor-activatable, and ubiquitously expressed NHE known to regulate intracellular pH and cellular volume. NHE2, NHE3, and NHE4 are, however, restricted in their tissue distribution, suggesting roles in specialized functions of these epithelial tissues. In this review we present and discuss the most recent advances in the molecular and biochemical features, hormonal and growth factor activation, specific expression, and membrane sorting of the members of this NHE family. PMID- 7864068 TI - Bioelectric characteristics of exon 10 insertional cystic fibrosis mouse: comparison with humans. AB - Two important issues that can be addressed by animal models are disease pathogenesis and the testing of new treatments, including gene therapy. How closely these models mimic the relevant disorder in humans will determine their usefulness. This study examines how closely the characteristic bioelectric features of cystic fibrosis (CF) are reproduced in the airways and intestinal tract of the exon 10 insertional mutant mouse (cf/cf). In agreement with CF subjects these cf/cf mutant mice demonstrate the following: 1) reduced adenosine 3',5'-cyclic monophosphate-related chloride secretion throughout the respiratory and intestinal tracts both in vivo and in vitro, 2) calcium-related chloride secretion that is preserved in the airways but reduced in the intestine, and 3) a more negative nasal potential difference and increased amiloride response compared with wild-type animals, likely to relate to increased sodium absorption. In contrast to humans, sodium absorption is not increased in the small intestine and is reduced in the trachea of the cf/cf mice. We conclude that the majority of the salient electrophysiological features of CF required for studies of pathogenesis or testing of new treatments are present in these cf/cf mice. PMID- 7864069 TI - A simple biochemical approach to quantitate rough endoplasmic reticulum. AB - In this report we demonstrate that the changes in size of the rough endoplasmic reticulum (RER) can be determined by quantifying the membrane-bound ribosomal population separated by cell fractionation and sucrose density gradient analysis. Total cell membranes, rather than microsomes, were used as the source of membrane bound ribosomes to eliminate potential losses during the preparation of microsomes. Bound ribosomes were assayed after quantitative release and recovery from total cell membranes using puromycin in the presence of high-salt buffer. Using this analysis, we demonstrate a 4.2-fold increase in RER in estrogen treated male Xenopus laevis liver. Furthermore, we show that the ratio of the distribution of free to membrane-bound ribosomes in a nonsecretory cell line (HeLa) was 3.3, while this ratio in a secretory cell line (AR42J) was 1.2, indicating that cells active in secretion contain more RER. We suggest that this biochemical technique provides a simpler assay to detect changes in the size of the RER. PMID- 7864070 TI - Iodoacetate-induced skeletal muscle contracture: changes in ADP, calcium, phosphate, and pH. AB - The effects of iodoacetic acid (IAA) and ischemic contraction were studied in rat extensor digitorum longus muscles. Ischemic stimulation of IAA-treated muscles produced contracture. We measured total muscle water content, distribution of water between intracellular and extracellular spaces, creatine concentration ([Cr]), creatine phosphate concentration ([PCr]), [ATP], [Pi], intracellular pH, and intracellular Ca2+ concentration ([Ca2+]i) at the onset of contracture. [ADP] was calculated from the equilibrium of the creatine kinase reaction using the measured values of [ATP], [PCr], [Cr], and pH. At the onset of contracture there was a 75% reduction of [PCr], a 12-fold increase in [ADP], and an 11-fold increase in [Ca2+]i compared with unstimulated IAA-treated muscles. [ATP] was not depleted at contracture compared with unstimulated IAA-treated muscles, and [Pi] increased less in muscles at contracture compared with stimulated control muscles. The persistent tension in contractures probably resulted from increased [Ca2+]i combined with increased myofibrillar Ca2+ sensitivity due to elevated [ADP] and relatively reduced intracellular acidification and [Pi]. PMID- 7864071 TI - Troponin I isoforms and differential effects of acidic pH on soleus and cardiac myofilaments. AB - Differences in pH sensitivity of tension generation between developing and adult cardiac myofilaments, which contain the same isoform of troponin C (TnC), have been proposed to be due to troponin I (TnI) isoform switching from the slow skeletal (ss) to cardiac (c) TnI isoforms (21). We investigated the effects of acidic pH on Ca(2+)-activation of force in chemically skinned preparations of adult rat trabeculae and single soleus fibers that also share the same TnC isoform. Compared with the soleus fibers, trabeculae demonstrated a greater suppression of tension and a rightward shift in pCa50 (-log half-maximally activating molar Ca2+ concentration) when pH was decreased from 7.0 to 6.2. The pH-induced shift in pCa50 in soleus fibers did not change with sarcomere length. Troponin subunit interactions were also investigated, using cardiac troponin C (cTnCIA) labeled with a fluorescent probe, 2-(4'-iodoacetamidoanilino) naphthalene-6-sulfonic acid. Under acidic conditions, cTnCIA demonstrated a decrease in Ca(2+)-affinity. This decrease was amplified both in the binary complex cTnCIA-cTnI and in the complex cTnCIA-cTnI-cTnT-tropomyosin to the same extent. In contrast, substitution of ssTnI for cTnI in these complexes produced the same decrease in Ca2+ affinity in response to acidic pH as cTnCIA alone. These results support our hypothesis that differential effects of pH on tension generation and Ca2+ sensitivity between soleus fibers and trabeculae are due to the presence of different isoforms of TnI. PMID- 7864072 TI - Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells. AB - Glucocorticoids have an inhibitory effect on inflammatory and immune responses, and this may be through the modulation of transcription factor binding to DNA. The interaction of the transcription factors, activator protein-1 (AP-1), nuclear factor kappa B (NF kappa B), and cAMP-responsive element binding protein (CREB) with DNA and glucocorticoid receptors (GR) was analyzed in human peripheral blood mononuclear cells by gel mobility shift assays. TNF-alpha, IL-1 beta and phorbol myristate acetate (PMA) treatment increased AP-1 and NF kappa B DNA binding by up to 200% but decreased CREB binding (38%) over a 60-min time course. Dexamethasone produced a rapid and sustained increase in glucocorticoid response element binding and a concomitant 40-50% decrease in AP-1, NF kappa B, and CREB DNA binding that was blocked by combined dexamethasone and cytokine or PMA treatment. These latter effects were due to increases in the nuclear localization of GR, not to reduced amounts of the other transcription factors. This suggests that in these cells GR within the nucleus interacts with cytokine-stimulated transcription factors by the process of cross coupling. This may be an important molecular site of steroid action. PMID- 7864073 TI - G protein-mediated suppression of L-type Ca2+ current by interleukin-1 beta in cultured rat ventricular myocytes. AB - The effect and possible signal transduction pathway of interleukin-1 beta (IL-1 beta) on the L-type Ca2+ current (ICa,L) in cultured adult rat ventricular myocytes were examined using whole cell patch-clamp techniques. When myocytes were internally dialyzed with a solution containing GTP, IL-1 beta caused a concentration-dependent decrease in the peak ICa,L (Ba2+ as the charge carrier). IL-1 beta did not significantly alter the voltage dependence of the peak ICa,L nor the steady-state inactivation and activation, but did slightly slow the rate of inactivation. In myocytes dialyzed with solutions without GTP or including guanosine 5'-O-(2-thiodiphosphate) to replace GTP, IL-1 beta had no effect on ICa,L. In contrast, when guanosine 5'-O-(3-thiotriphosphate) was used to replace GTP, the suppression of ICa,L induced by IL-1 beta remained. Preincubation of myocytes with pertussis toxin (PTX), which completely abolished the acetylcholine effect on isoproterenol-stimulated ICa,L, had no effect on the inhibitory action of IL-1 beta on ICa,L. We conclude that in cultured rat ventricular myocytes, IL 1 beta suppresses ICa,L via a PTX-insensitive G protein. PMID- 7864074 TI - Na+ channels in membrane vesicles from intralobular salivary ducts. AB - Electrical potential-driven 22Na+ fluxes were measured in membrane vesicles prepared from male and female rat submandibular intralobular ducts. A relatively temperature-independent (Q10 = 1.45 +/- 0.15), amiloride-inhibitable (mean affinity constant approximately 1 microM), rheogenic Na+ transport pathway was observed. The relative potency of amiloride analogues for inhibition of this pathway was amiloride > ethylisopropyl-amiloride > phenamil, similar to that of the "low-amiloride-affinity" Na+ channel recently observed in a number of other tissues. These results are consistent with the existence of the apical Na+ channel thought to be involved in intralobular ductal salt reabsorption. No significant difference was found in the magnitude or pharmacology of electrogenic Na+ fluxes in vesicles prepared from male and female rat intralobular ducts, suggesting that the sexual dimorphism observed in this tissue is not reflected at the level of the apical membrane Na+ channel. Amiloride-sensitive 22Na+ fluxes in intralobular ductal membranes were of the same magnitude as 22Na+ fluxes measured in similarly prepared and assayed vesicles from the toad bladder, a tissue thought to be a rich source of amiloride-sensitive Na+ channels. PMID- 7864075 TI - Angiotensin-converting enzyme inhibition, intracellular Na+, and Na(+)-K+ pumping in cardiac myocytes. AB - Angiotensin-converting enzyme (ACE) inhibitors can reduce cardiac mass in both clinical and experimental cardiac hypertrophy. Because cytoplasmic Na+ and pH have been implicated as regulators of cell growth, we examined the effect of treatment with an ACE inhibitor on intracellular Na+ activity (alpha iNa) and pH (pHi) in the heart. After treatment of rabbits with captopril for 8 days alpha iNa was reduced relative to controls (3.6 +/- 0.4, n = 8, vs. 8.2 +/- 0.4 mM, n = 9, P < 0.001), whereas pHi was unchanged. To account for the difference in alpha iNa we measured electrogenic Na(+)-K+ pump activity in single isolated myocytes. Treatment with captopril increased pump currents at near-physiological levels of intracellular Na+ but had no effect at near-saturating levels of Na+. A similar increase in Na(+)-K+ pump activity occurred in rabbits treated with another ACE inhibitor, enalapril, but not with the vasodilator, hydralazine. We speculate that a decrease in alpha iNa after treatment with captopril may contribute to the well-documented ability of ACE inhibitors to reduce cardiac mass. PMID- 7864076 TI - cGMP antagonizes angiotensin-mediated phosphatidylcholine hydrolysis and C kinase activation in mesangial cells. AB - Previous studies from this laboratory have shown that in cultured rat mesangial cells (MC), angiotensin II (ANG II) mediates its effects via activation of phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphatidylcholine specific phospholipase C (PC-PLC) and phospholipase D (PC-PLD). In addition, guanosine 3',5'-cyclic monophosphate (cGMP)-elevating maneuvers that stimulate particulate and soluble guanylate cyclase [atrial natriuretic factor (ANF) and sodium nitroprusside (SNP), respectively] antagonize ANG II-mediated PI-PLC activation. The current study explored whether cGMP impairs ANG II-mediated PC PLC and PLD activity. The ANG II-stimulated release of the water-soluble metabolites of PC breakdown (phosphorylcholine and choline) was blocked by ANF and SNP. ANG II-stimulated phosphatidic acid and phosphatidylethanol formation were significantly reduced by ANF and SNP, confirming that cGMP blunted PLD activity. The inhibitory effect of cGMP on PLD could be reversed by N-(2 [methylamino]ethyl)-5-isoquinolinesulfonamide, a blocker of cGMP-dependent protein kinase. In parallel experiments, ANF and SNP abrogated sustained diacylglycerol (DAG) accumulation derived from ANG II stimulation of PC hydrolysis, confirming that cGMP diminished PC-PLC activity. Inhibition of PC derived DAG accumulation by cGMP was associated with a concomitant decrement in ANG II-mediated translocation of protein kinase C (PKC) activity from the cytosol to the membrane. In summary, in MC, cGMP antagonizes ANG II-mediated PC hydrolysis, DAG formation, and PKC activation. We propose that cGMP-mediated inhibition of phospholipid metabolism and PKC translocation plays an important role in MC vasorelaxation. PMID- 7864077 TI - Leukoregulin is a potent inducer of hyaluronan synthesis in cultured human orbital fibroblasts. AB - Leukoregulin, a 50-kDa glycoprotein lymphokine, can regulate the extracellular matrix in dermal fibroblasts. Here we investigate the effects of leukoregulin on the synthesis of glycosaminoglycans in human orbital fibroblasts. We demonstrate that leukoregulin enhances the incorporation of [3H]glucosamine into glycosaminoglycans. The effect is dose dependent in the concentration range tested (0.1-2 U/ml), is maximal at 1 U/ml, and is time dependent. [3H]glycosaminoglycan accumulation is enhanced 7.67 +/- 1.23-fold (SE, n = 7) in orbital fibroblast strains. Pulse-chase studies indicate that this enhanced accumulation is not a result of a decreased rate of macromolecular degradation. Radiolabeled material induced by leukoregulin is sensitive to Streptomyces hyaluronidase digestion. Dexamethasone (10(-8) M) and cycloheximide (10 micrograms/ml) can block the cytokine's stimulation of hyaluronan synthesis. [35S]sulfate incorporation into glycosaminoglycan is unaffected by leukoregulin. In dermal fibroblasts, leukoregulin increased hyaluronan synthesis 3.66 +/- 0.37 fold (n = 5 strains, P < 0.02 compared with orbit). The increase in hyaluronan synthesis in orbital fibroblasts is substantially greater than that observed previously with other cytokines, making leukoregulin a candidate molecular trigger in Graves' ophthalmopathy. PMID- 7864078 TI - Permeation and gating properties of a cloned renal K+ channel. AB - The renal K+ channel (ROMK2) was expressed in Xenopus oocytes, and the patch clamp technique was used to assess its conducting and gating properties. In cell attached patches with 110 mM K+ in the bath and pipette, the reversal potential was near zero and the inward conductance (36 pS) was larger than the outward conductance (17 pS). In excised inside-out patches the channels showed rectification in the presence of 5 mM Mg2+ on the cytoplasmic side but not in Mg(2+)-free solution. Inward currents were also observed when K+ was replaced in the pipette by Rb+, NH4+, or thallium (Tl+). The reversal potentials under these conditions yielded a selectivity sequence of Tl+ > K+ > Rb+ > NH4+. On the other hand, the slope conductances for inward current gave a selectivity sequence of K+ = NH4+ > Tl+ > Rb+. The differences in the two sequences can be explained by the presence of cation binding sites within the channel, which interact with Rb+ and Tl+ more strongly and with NH4+ less strongly than with K+. Two other ions, Ba2+ and Cs+, blocked the channel from the outside. The effect of Ba2+ (1 mM) was to reduce the open probability of the channels, whereas Cs+ (10 mM) reduced the apparent single-channel current. The effects of both blockers are enhanced by membrane hyperpolarization. The kinetics of the channel were also studied in cell attached patches. With K+ in the pipette the distribution of open times could be described by a single exponential (tau 0 = 25 ms), whereas two exponentials (tau 1 = 1 ms, tau 2 = 30 ms) were required to describe the closed-time distribution. Hyperpolarization of the oocyte membrane decreased the open probability and tau 0, and increased tau 1, tau 2, and the number of long closures. The presence of Tl+ in the pipette significantly altered the kinetics, reducing tau 0 and eliminating the long-lived closures. These results suggest that the gating of the channel may depend on the nature of the ion in the pore. PMID- 7864079 TI - Osmotic regulation of synthesis of glycerophosphocholine from phosphatidylcholine in MDCK cells. AB - Glycerophosphocholine (GPC) is osmotically regulated in renal medullary cells and in cultured Madin-Darby canine kidney (MDCK) cells. Previously, it was shown that a high extracellular concentration of urea or NaCl causes these cells to accumulate large amounts of GPC. GPC is known to be a product of phosphatidylcholine (PC) catabolism. The purpose of the present experiments was to examine the role of changes in the rate of GPC synthesis from PC in hyperosmotically induced GPC accumulation. When 1-palmitoyl-2-lysophosphatidyl [methyl-3H]choline ([3H]LPC) is added to the medium, it is taken up by the cells and most of it is rapidly converted to PC. During a chase, 3H lost from PC appears almost exclusively in GPC and sphingomyelin. The rate of catabolism of PC is twofold greater in cells exposed to high NaCl (200 mosmol/kgH2O, added for 2 days) than in control or high-urea medium. Increased PC catabolism in NaCl treated cells is associated with a 2.6-fold increase in GPC synthesis from PC; sphingomyelin synthesis decreases, and total cell PC does not change. Also, neither total mass nor specific radioactivity of lysophosphatidylcholine changes. PC catabolism is unaffected by short (2 h) exposure to high NaCl or urea. To investigate the enzymatic basis for the increased PC catabolism in response to high NaCl, phospholipase activity was measured in cell homogenates with 1 palmitoyl-2-[1-14C]palmitoyl-PC as a substrate. Exposure of cells to high NaCl for 2 days (but not 2 h) increases activity 2.8-fold compared with control or high-urea medium. Lysophospholipase activity (measured with [3H]LPC as the substrate) is unchanged. The increased phospholipase activity occurs with dipalmitoyl PC, but not sn-2-arachidonyl PC, as a substrate. Collectively, these data suggest a role for a phospholipase, unrelated to the arachidonyl-selective enzyme, in the regulation of PC catabolism during accumulation of GPC induced by prolonged exposure to high extracellular NaCl. PMID- 7864080 TI - Downregulation of the oxytocin receptor on cultured astroglial cells. AB - Cultured astroglial cells obtained from rat fetal hypothalamus express oxytocin (OT) receptors, which have been previously characterized (Di Scala-Guenot and Strosser. Biochem. J. 284: 491-497, 1992), with a radioiodinated OT antagonist. In these cells, at steady-state binding at 37 degrees C, ice-cold acidic treatment released 10% of the bound ligand; with pronase treatment, 52% of the tracer was released. Because the binding was performed with an antagonist, one could assume that the radiolabeled ligand remains locked into the membrane in a state insensitive to the stripping agents rather than being internalized. Receptor downregulation induced by OT was concentration- and time-dependent, leading to a 72% loss of maximal binding capacity without changing the affinity of the receptor. On removal of OT the binding capacity recovered partially and the restoration process was blocked by monensin (20 microM) but not by cycloheximide (20 micrograms/ml), suggesting involvement of receptor recycling. Concerning the early mechanisms involved in the downregulation processes, uncoupling of the receptor from the G protein and the receptor phosphorylation by protein kinase C could be demonstrated. Treatment of the cells with the OT antagonist d(CH2)5OVT was shown to facilitate radioligand binding and to protect the receptor against OT-induced downregulation. PMID- 7864081 TI - Sensitive detection of myosin heavy chain composition in skeletal muscle under different loading conditions. AB - Different loading conditions were employed to study changes in myosin heavy chain (MHC) composition with the aid of a sensitive approach for separating and detecting MHC isoforms. Separation and detection of MHCs by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were achieved to a degree such that MHC composition is consistent with previous reports on functional and mRNA data. Neonatal MHC was detected at low levels in control, 14-day hindlimb unweighted (HU), and 28-day HU soleus muscles. Type IIa MHC remained unchanged in all groups, representing approximately 9% of total MHC present. Type IIb MHC was not detected in control but represented 3% of total MHC at both 14 and 28 days of HU. Type IIx MHC also was not detected in control but represented 6% of total MHC at 14 days HU, and increased to 14% of total MHC at 28 days HU (P < 0.05). Type I MHC decreased from 89% in control to 72% at 28 days HU (P < 0.05). Furthermore, the type I MHC band was separated into two bands of approximately equal content in all groups when low amounts of protein were loaded on gels. The decrease in type I MHC with HU could be attributed entirely to a decrease in the percentage of the band in the type I region with lower mobility, which corresponds to beta MHC. In addition, hypertrophied plantaris muscles demonstrated a fast-to-slow shift in MHC composition as evidenced by increased I, IIa, and IIx MHC and decreased IIb MHC expression. PMID- 7864082 TI - Regulation of Na+/H+ exchange activity by recruitment of new Na+/H+ antiporters: effect of calyculin A. AB - The Na+/H+ antiporter of trout red blood cells, beta-NHE, is activated by agonists of the adenosine 3',5'-cyclic monophosphate-dependent protein kinase A (PKA) and by those of protein kinase C (PKC). beta-NHE, once activated, shifts into a refractory state, accounting for its desensitization. It had previously been shown that desensitization is blocked and reversed by the protein phosphatase inhibitor okadaic acid (OA). In this study we examined the effect of another protein phosphatase inhibitor, calyculin A (CIA). CIA was at least 10 times more potent than OA in blocking beta-NHE desensitization, suggesting that desensitization is controlled by phosphatase-1. Furthermore, CIA alone induced a large Na+/H+ exchange in unstimulated red blood cells, a property not shared by OA. The characteristics of ClA-induced Na+/H+ exchange are very different from those of the exchange triggered by activation of beta-NHE by PKA or PKC agonists, i.e., a flat pH dependence and total insensitivity to PKA and PKC inhibitors. Simultaneous addition of maximal concentrations of ClA and catecholamine produced an additive stimulation of the Na+/H+ exchange, consistent with the interpretation that these agents act on two distinct pools of exchangers. Screening of different cDNA libraries suggested that only one isoform of antiporter exists in the trout red blood cell; it therefore seems likely that regulation of the Na+/H+ antiporter beta-NHE involves a recycling mechanism. The reasons why intracellular beta-NHE show different properties from membrane beta NHE are discussed. PMID- 7864083 TI - Characterization of plasminogen system on rat yolk sac carcinoma (L2) cells. AB - The plasminogen (Plg) system on rat yolk sac carcinoma (L2) cells was characterized by zymography, Western and immunoprecipitation analysis, reverse transcriptase polymerase chain reaction, binding, and activity assays. The L2 cells produced tissue Plg activator but not urokinase Plg activator and contained RNA for Plg activator inhibitor 1, but Plg activator inhibitor 1 was not detectable by zymography or Western analysis and contained the receptor for urokinase Plg activator. Plg bound to the cells in a saturable manner when plasmin inhibitors were present with a dissociation constant of 1.34 +/- 0.18 x 10(-6) M and 1.54 +/- 0.25 x 10(7) sites/cell. Immunoprecipitation analysis showed that Plg was binding to gp330, a known Plg receptor. Once bound to the L2 cells, Plg was activated by tissue Plg activator to plasmin in a time- and concentration-dependent manner. Under saturating Plg conditions, most of the plasmin produced was released into the medium. Inhibition of plasmin activation occurred when Plg activator inhibitor 1, anticatalytic tissue Plg activator antibody, or Heymann nephritis autoantibody was present. PMID- 7864084 TI - Subcellular localization of PEPCK and metabolism of gluconeogenic substrains of renal cell lines. AB - The two gluconeogenic substrains of renal epithelial cells, LLC-PK1-FBPase+ and OKGNG+, have been shown to differ markedly in their metabolism of lactate and pyruvate. OKGNG+ cells consumed lactate as well as pyruvate at high rates in contrast to LLC-PK1-FBPase+ cells, which failed to take up or utilize lactate. (Aminooxy)acetate (AOA), an inhibitor of transamination reactions, was used to further delineate these differences. Lactate consumption of OKGNG+ cells was significantly inhibited by AOA, whereas pyruvate consumption by LLC-PK1-FBPase+ cells was slightly stimulated. Growth of OKGNG+ cultures, however, could be achieved on lactate in the presence of AOA. From these results it was concluded that the cell strains might differ in the subcellular distribution of phosphoenolpyruvate carboxykinase (PEPCK). LLC-PK1-FBPase+ cells may express both mitochondrial and cytosolic PEPCK isoenzymes, whereas OKGNG+ cells express only the mitochondrial isoenzyme. This was tested by directly assaying PEPCK activity in subcellular fractions of the cells. In OKGNG+ cells PEPCK activity fractionated with the mitochondrial marker glutamate dehydrogenase; however, in LLC-PK1-FBPase+ cells two-thirds of PEPCK activity was found in the cytosol. In LLC-PK1-FBPase+ cells, PEPCK activity increased twofold on incubation in acidic culture medium (pH 6.9) for 18 h, in contrast to the PEPCK activity in OKGNG+ cells. Northern blot analysis using cDNA probes specific for the mitochondrial and cytosolic PEPCK mRNAs confirmed the enzyme activity data. In LLC-PK1-FBPase+ cells strong expression of cytosolic PEPCK mRNA was observed, whereas in OKGNG+ cells only very low levels could be detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864085 TI - Smooth muscle stretch-activated phospholipase C activity. AB - Rabbit aortic muscles were stretched from a holding length of 0.6 maximum length (Lmax) to lengths as great as 1.0 Lmax and the new length maintained. When muscles were stretched to 1.0 Lmax, inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,4-bisphosphate [Ins(1,4)P2] contents were increased at 375 ms (uncorrected for freezing time) poststretch to 209 +/- 27 and 139.8 +/- 12% (SE), respectively, of control values. Increases in Ins(1,4,5)P3 and Ins(1,4)P2 contents reached an apparent maximum at approximately 500 ms, i.e., to 243.7 +/- 15.8 and 180.9 +/- 16.2% of control, and were decreased to near control levels at 1,700 ms poststretch. The stretch threshold for phospholipase C (PLC) activation was 0.85 Lmax. The latency to onset of PLC activation, correcting for the time for freezing, was 275 to 375 ms. Maximal PLC activity was 91 pmol.s-1.100 nmol total lipid P(i)-1, which corresponded to 10% of total phosphatidylinositol bisphosphate being hydrolyzed per second. The mechanism of stretch-activated PLC activity involved influx of Ca2+ via gadolinium-sensitive ion channels, but not via nifedipine-sensitive ion channels. PMID- 7864086 TI - Changes in contractile protein mRNA accumulation in response to spaceflight. AB - Ten rats were exposed to 9 days of zero gravity aboard the National Aeronautics and Space Administration SLS-1 space mission (June 1991). Levels of fast and slow isoform mRNAs from six contractile protein gene families were quantified in the flight soleus and extensor digitorum longus (EDL) muscles. The gene families studied were myosin light chain-1 (MLC-1), myosin light chain-2 (MLC-2), troponin (Tn) T, TnI, TnC, and tropomyosin. In the EDL muscle there was no change in slow mRNA levels with a general increase in fast mRNA levels from 23 to 232%. Changes in slow mRNA levels were seen in the flight soleus muscle with TnCslow and TnTslow levels increasing slightly, and MLC-1slow a, MLC-1slow b, TnIslow, alpha Tmslow, and MLC-2slow levels decreasing. All fast mRNA levels increased in the flight soleus muscle from 170 to 1,100%. We can conclude that exposure to zero gravity results in 1) a general increase in fast mRNA levels in both fast and slow muscles and 2) differing directional changes in slow mRNA accumulation in the soleus muscle. PMID- 7864087 TI - Effect of physiological ADP concentrations on contraction of single skinned fibers from rabbit fast and slow muscles. AB - To directly assess the possible role of ADP in muscle fatigue, we have studied the effect of physiological MgADP levels on maximum Ca(2+)-activated isometric force and unloaded shortening velocity (Vus) of single skinned fiber segments from rabbit fast-twitch (psoas) and slow-twitch (soleus) muscles. MgADP concentration was changed in a controlled and well-buffered manner by varying creatine (Cr) in solutions, which also contained MgATP, phosphocreatine (PCr), and creatine kinase (CK). To quantify ADP as a function of Cr added, we determined the apparent equilibrium constant (K') of CK for the conditions of our experiments (pH 7.1, 3 mM Mg2+, 12 degrees C): K' = (sigma [Cr]. sigma [ATP])/(sigma [PCr]. sigma [ADP]) = 260 +/- 3 (SE). In this manner, ADP was altered essentially as occurs during stimulation in vivo but without the concomitant changes in pH and P(i), which affect force and Vus. As ADP (and Cr) was increased, force and Vus decreased in both fiber types; at the highest ADP level used, 200 microM, normalized force was 96.6 +/- 1.7% for psoas (n = 6) and 93.7 +/- 2.8% for soleus (n = 6), and Vus was 80.4 +/- 2.4% for psoas and 91.3 +/ 7.7% for soleus. Diffusion-reaction calculations indicated that radial gradients of metabolite concentrations within fibers could not explain the small effects of ADP on fiber mechanics, and experiments verified that metabolite levels were well buffered within fibers by the CK reaction. Exogenous CK was added to bathing solutions at 290 U/ml, threefold above that necessary to maintain Vus independent of CK concentration; in the absence of PCr and exogenous CK, at least a fourfold increased MgATP was necessary to maintain Vus at the control level. Adenylate kinase activity was not detectable; thus myofibrillar adenosine-triphosphatase and exogenous CK activities were the major determinants of nucleotide levels within activated cells. Cr alone (in absence of PCr and exogenous CK) also decreased force and Vus, presumably by a nonspecific mechanism. Over the physiological range, altered ADP had little or no effect on force or Vus in well buffered conditions. It is therefore likely that other factors decrease force and Vus during muscular fatigue. PMID- 7864088 TI - Modulation of a potassium conductance in developing skeletal muscle. AB - K+ conductances dominate and potentially modulate the resting potential of skeletal muscle cells. The expression and modulation of a major K+ conductance were examined during in vitro differentiation of the mouse myoblast cell line C2C12. The inwardly rectifying K+ conductance (IKi) increased from unmeasurable levels in undifferentiated myoblasts to approximately 1.56 +/- 0.51 nA (n = 17) in myoballs derived from myotubes at 5 days after induction of differentiation. The inward rectifier was subject to modulation by intracellular signals. Exposure of cytoplasm to guanosine 5'-O-(3-thiotriphosphate) during whole cell recording produced a concentration (5-100 microM)- and time (1-20 min)-dependent inhibition of the mean conductance. Elevation of intracellular free Ca2+ (> 200 nM) also inhibited IKi. These findings demonstrate a potential mechanism for modulation of the resting potential of muscle fibers via the control of skeletal muscle IKi. PMID- 7864089 TI - Perichondrial localization of ETA receptor in rat tracheal and xiphoid cartilage and in fetal rat epiphysis. AB - Autoradiographic studies using 125I-labeled endothelin-1 (ET-1) on sections of rat cartilage tissues, including the trachea, xiphisternum, and fetal rat epiphysis, revealed dense localization of endothelin receptors in the perichondrium. In contrast, the binding of ET-1 was not detected in the chondrocytes, cartilage matrix, and other connective tissues of the cartilage tissues tested. The perichondrial binding of 125I-ET-1 was completely abolished with BQ-123 [an endothelin receptor subtype A (ETA) antagonist] but not with BQ 3020 (an ETB agonist), and we demonstrated the perichondrial localization of ETA receptors. [3H]thymidine incorporation in vitro was significantly increased in rat xiphoid cartilage tissues exposed to ET-1. These findings suggest that the ET 1/ETA receptor system plays an important role in regulating cartilage metabolism and endochondral bone formation. PMID- 7864090 TI - Depletion and filling of intracellular calcium stores in vascular smooth muscle. AB - In vascular smooth muscle, binding of vasoactive substances to surface membrane receptors leads to a rise of intracellular cytoplasmic Ca2+ and to contraction. Cytoplasmic free Ca2+ concentration ([Ca2+]i) increases through release of Ca2+ from intracellular stores and Ca2+ entry through surface membrane ion channels. Membrane-permeant and membrane-impermeant forms of fura 2 were used to distinguish changes in intracellularly stored Ca2+ ([Ca2+]s) from changes in [Ca2+]i. The spatiotemporal patterns of the movement of Ca2+ between these two cellular compartments in cultured vascular smooth muscle cells (A7r5 cell line) were visualized with digital imaging fluorescence microscopy. The Ca2+ stores were localized by double staining with a fluorescent organelle-specific dye and the Ca2+ indicator. [Ca2+]s was measured after accumulation of the membrane permeant form of fura 2 inside the stores and quenching of the fura 2 fluorescence in the cytoplasmic compartment with manganese. Stimulation with vasopressin led to a transient increase of [Ca2+]i and a concomitant decrease of [Ca2+]s. After stimulation with vasopressin, [Ca2+]i returned rapidly to normal resting levels, whereas the recovery of [Ca2+]s occurred on a much slower time scale. The refilling pathway of depleted stores involved Ca2+ entry into the bulk cytoplasmic compartment before uptake into the stores. PMID- 7864091 TI - Mechanical power and myosin composition of soleus and extensor digitorum longus muscles of ky mice. AB - Muscles of ky/ky homozygote mice exhibit neonatal muscle fiber necrosis and regeneration with subsequent motor nerve sprouting and development of a prominent kyphoscoliosis from approximately 100 days onward. Soleus and extensor digitorum longus (EDL) muscles from ky mice weighted < 50% of control muscles from age matched NMRI mice. Maximal tetanic force was more reduced in soleus than in EDL. In EDL, the velocity constant of the force-velocity relation, maximal velocity, twitch time-to-peak, and isomyosin content were normal at all ages. The early mechanical changes seen in ky soleus muscles (47 day) were not accompanied by significant alterations in isomyosin or myosin heavy- and light-chain composition, since ky and NMRI expressed slow-twitch native myosin 2 (SM2, type I fibers) and intermediate-twitch native myosin (IM, type IIa fibers). Adult ky soleus (172 day) showed wholesale loss of IM and sole expression of SM2. This is sufficient to account for the markedly slowing of the force-velocity relation and the twitches observed in adult ky soleus. We propose that since shifts in muscle type only occurred in soleus, this reflects the persistent requirement to withstand the force of gravity. PMID- 7864092 TI - Further evidence of incomplete neural control of muscle properties in cat tibialis anterior motor units. AB - To examine the influence of a motoneuron in maintaining the phenotype of the muscle fibers it innervates, myosin heavy chain (MHC) expression, succinate dehydrogenase (SDH) activity, and cross-sectional area (CSA) of a sample of fibers belonging to a motor unit were studied in the cat tibialis anterior 6 mo after the nerve branches innervating the anterior compartment were cut and sutured near the point of entry into the muscle. The mean, range, and coefficient of variation for the SDH activity and the CSA for both motor unit and non-motor unit fibers for each MHC profile and from each control and each self-reinnervated muscle studied was obtained. Eight motor units were isolated from self reinnervated muscles using standard ventral root filament testing techniques, tested physiologically, and compared with four motor units from control muscles. Motor units from self-reinnervated muscles could be classified into the same physiological types as those found in control tibialis anterior muscles. The muscle fibers belonging to a unit were depleted of glycogen via repetitive stimulation and identified in periodic acid-Schiff-stained frozen sections. Whereas muscle fibers in control units expressed similar MHCs, each motor unit from self-reinnervated muscles contained a mixture of fiber types. In each motor unit, however, there was a predominance of fibers with the same MHC profile. The relative differences in the mean SDH activities found among fibers of different MHC profiles within a unit after self-reinnervation and those found among fibers in control muscles were similar, i.e., fast-2 < fast-1 < or = slow MHC fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864093 TI - A new hypoglycemic agent, A-4166, inhibits ATP-sensitive potassium channels in rat pancreatic beta-cells. AB - Effects of a new hypoglycemic drug, N-[trans-4-isopropylcyclohexy-carbonyl]-D phenylalanine (A-4166), on membrane current were investigated using the patch clamp technique in single pancreatic beta-cells isolated from rats. A-4166, at a concentration of 10 microM, depolarized membrane potential of beta-cells and evoked action potentials in the presence of 2.8 mM glucose. The single ATP sensitive K+ channel (K-ATP channel) current recorded in cell-attached membrane patches was reversibly inhibited by A-4166 (> 0.1 microM) without a change in the single-channel conductance of the K-ATP channel. Both A-4166 and tolbutamide inhibited the whole cell K-ATP channel current with half-maximum inhibition (IC50) of 0.23 and 12.8 microM, respectively (Hill coefficient = 1). In inside out membrane patches, the IC50 with A-4166 occurred at 4.5 nM, in contrast to 0.7 microM for tolbutamide. A-4166 did not affect L- and T-type Ca2+ channels or the time-dependent outward current. We conclude that A-4166 specifically blocks the K ATP channel and that the blockade is more potent than that of tolbutamide. The action of A-4166 underlies the mechanism by which the drug stimulates insulin secretion from beta-cells. PMID- 7864094 TI - Hepatic denervation does not significantly change the response of the liver to glucagon in conscious dogs. AB - In view of the increasing frequency of liver transplantation, and the importance of glucagon in the minute-to-minute regulation of glucose production, we assessed the effect of hepatic denervation on the liver's response to a physiological rise in glucagon in 18-h fasted dogs. Before study (2 wk), the dogs underwent liver denervation (DN; n = 6) or sham operation (SH; n = 5). Endogenous insulin and glucagon secretion were inhibited using somatostatin, and the two hormones were replaced intraportally in basal amounts. After the control period the glucagon infusion rate was tripled for 3 h. Glucagon increased from 41 +/- 8 to 128 +/- 8 and 54 +/- 4 to 129 +/- 9 pg/ml in SH and DN, respectively (P < 0.05), causing tracer-determined glucose production to increase from 2.5 +/- 0.1 to 4.9 +/- 0.5 and 2.3 +/- 0.1 to 5.8 +/- 0.8 mg.kg-1.min-1 by 15 min, respectively (P < 0.05). Glucose clearance fell slightly during glucagon infusion in DN, causing a somewhat greater increase in the plasma glucose level (to 175 +/- 15 vs. 207 +/- 20 mg/dl). The changes in gluconeogenic efficiency increased 65-90% in both groups (P < 0.05). In conclusion, denervation of the liver failed to significantly alter the metabolic response of that organ to a half-maximally effective increment in the plasma glucagon level. PMID- 7864095 TI - Modulation of Ca2+ influx in the ovine somatotroph by growth hormone-releasing factor. AB - Voltage-gated Ca2+ currents were recorded using the nystatin-perforated whole cell recording configuration on the ovine somatotrophs. With the use of Ca(2+) tetraethylammonium chloride bath solution and Cs+ electrode solution, two types of Ca2+ currents were obtained with a predominant long-lasting (L) current blocked by nifedipine. A transient (T) current was isolated in the presence of nifedipine (3 microM) and was not blocked by omega-conotoxin (5 microM), but diminished to 47 +/- 5% of control by Ni2+ (0.3 mM) or to 52 +/- 10% of control by amiloride (0.5 mM). The nifedipine-blockable L-type current was not affected by omega-conotoxin (5 microM); it was, however, attenuated to 80 +/- 4% of control by Ni2+ (0.3 mM) and to 48 +/- 6% of control by amiloride (0.5 nM). Cd2+ (1 mM) totally prevented both T and L currents. Application of growth hormone releasing factor (GRF, 10 nM) reversibly increased the amplitude of both Ca2+ currents without modifying their kinetic properties. The effect of GRF was observed approximately 30 s after application, peaked (142 +/- 11% of control, n = 5) rapidly, and lasted > 10 min if GRF treatment was continuous. Intracellular Ca2+ concentration ([Ca2+]i) was increased by GRF (10 nM) within seconds, reaching a peak within 30 s and lasting > 250 s. Blockade of Ca2+ channels (Cd2+, 1 mM) or the use of Ca(2+)-free solution reduced basal [Ca2+]i and significantly (P < 0.05) diminished the effect of GRF on [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864096 TI - In vitro and in vivo analysis of murine lipoprotein lipase gene promoter: tissue specific expression. AB - Lipoprotein lipase, an enzyme of central importance to lipid metabolism, is most abundant in adipose tissues, cardiac and skeletal muscle, and portions of the brain. The current work examined the murine lipoprotein lipase promoter using transient transfection, gel-retention analyses, and transgenic mice. Maximum expression of the luciferase reporter gene in transfected cells was observed with -101 bp of the promoter. Nuclear extracts from tissues expressing lipoprotein lipase contained DNA binding proteins that recognize the CCAAT box (-64 bp) and an octamer motif (-46 bp); this combination of factors was absent in nonexpressing tissues. Transgenic mice from three of five founders prepared with 1,824-bp promoter constructs expressed the luciferase reporter gene at highest levels in brown adipose tissue and brain. These findings suggest that the -1,824 bp promoter region contains sequence elements responsible for the tissue-specific transcription of lipoprotein lipase in vivo. PMID- 7864097 TI - Tumor necrosis factor mediates zymosan-induced increase in glucose flux and insulin resistance. AB - Intraperitoneal injection of sterile zymosan produces an inflammatory response ultimately resulting in multiple-organ failure. The purpose of the present study was to characterize the hormonal and metabolic alterations produced as a result of this nonbacterial nonendotoxic inflammatory agent and to determine whether these changes were mediated by enhanced production of tumor necrosis factor (TNF). Rats were injected intraperitoneally with either zymosan or saline and studied 18 h later. Under basal conditions, zymosan-injected rats were euglycemic but showed a 43% increase in hepatic glucose production and peripheral glucose uptake. The enhanced glucose flux in zymosan-treated rats was associated with elevations in plasma insulin (45%), glucagon (5-fold), corticosterone (2-fold), epinephrine (34%), and norepinephrine (115%). In vivo studies using 2 deoxyglucose (2-DG) demonstrated that the zymosan-induced increase in whole body glucose disposal resulted from an enhanced uptake by skeletal muscle (68%), diaphragm (3.7-fold), liver (144%), spleen (52%), and fat (133%). Under euglycemic hyperinsulinemic conditions, zymosan-treated rats exhibited both hepatic and peripheral insulin resistance, with the latter resulting from a decreased insulin-mediated glucose uptake by skeletal muscle, heart and diaphragm. Arterial TNF levels were increased by 1 h and remained elevated throughout the experimental protocol. Pretreatment of rats with a neutralizing anti-TNF antibody before zymosan prevented the elevation in basal glucose flux and attenuated the insulin resistance. We conclude that the inflammatory state induced by zymosan enhances basal glucose turnover and impairs insulin action and that these changes appear to be largely due to the enhanced endogenous production of TNF. PMID- 7864098 TI - Exercise induces human lipoprotein lipase gene expression in skeletal muscle but not adipose tissue. AB - Lipoprotein lipase (LPL) is regulated by exercise in humans, but the effects of exercise on LPL expression in different tissues and the molecular mechanisms involved are unclear. We assessed the effects of 5-13 consecutive days of supervised exercise on tissue LPL expression as well as fasting plasma lipids and lipoproteins in 32 sedentary, weight-stable adult men. In skeletal muscle, exercise training increased the mean LPL mRNA level by 117% (P = 0.037), LPL protein mass by 53% (P = 0.038), and total LPL enzyme activity by 35% (P = 0.025). In adipose tissue, mean LPL mRNA, protein mass, and activity did not change. Exercise decreased triglycerides [from 172 +/- 4.3 to 127 +/- 3.2 (SE) mg/dl, P = 0.002], total cholesterol (from 188 +/- 1.2 to 181 +/- 1.0 mg/dl, P = 0.011), and very low-density lipoprotein-cholesterol (from 30.1 +/- 0.9 to 22.0 +/- 0.8, P = 0.004) and increased high-density lipoprotein cholesterol (HDL-C; from 43.4 +/- 0.35 to 45.0 +/- 0.37, P = 0.030) and HDL2-C (from 6.6 +/- 0.21 to 7.7 +/- 0.19, P = 0.021). Changes in muscle but not adipose tissue heparin releasable LPL activity were inversely correlated (r = -0.435, P < 0.034) with changes in triglycerides. These data suggest the existence of an exercise stimulus intrinsic to skeletal muscle, which raises LPL activity in part by pretranslational mechanisms, a process that contributes to the improvement in circulating lipids seen with physical activity. PMID- 7864099 TI - Comparison of ANG II in fetal and pregnant sheep: metabolic clearance and vascular sensitivity. AB - Fetal sheep appear less responsive to infused angiotensin II (ANG II) than pregnant ewes. This may reflect a greater fetal metabolic clearance rate (MCRANGII) and thus lower plasma ANG II levels. We therefore determined fetal MCRANGII, half-life (T1/2), and placental removal of ANG II. Fetal sheep (n = 13; 113-139 days of gestation) received 0.573-5.73 micrograms ANG II/min iv for 30 min while arterial pressure and heart rate were monitored. Serial blood samples were obtained before and during a 30-min infusion to measure ANG II and calculate MCRANGII and after stopping the infusion to determine T1/2. MCRANGII was similar across gestation and at doses < or = 2.29 micrograms/min (683 +/- 49 vs. 74 +/- 5 ml.min-1.kg-1 for adults) but was 30-40% lower with 5.73 micrograms ANG II/min (494 +/- 57 ml.min-1.kg-1, P < 0.05). T1/2 was 15-21 s. Fetal placental ANG II removal averaged 87 +/- 3 vs. 20 +/- 6% for uteroplacental removal; this was unaffected by dose and was linear with plasma ANG II levels, and saturation was not evident. Plasma ANG II levels rose proportionally with infusion rate and did not change significantly over time; thus fetal plasma ANG II concentrations can be predicted from MCRANGII. Measured and predicted ANG II levels at each infusion rate and time point were similar: r = 0.87, slope = 0.87 (P < 0.001). At equivalent predicted plasma ANG II levels fetal and maternal pressor responses were similar (P > 0.1); however, increases in umbilical vascular resistance exceeded those in uteroplacental vascular resistance (P < 0.03). Fetal MCRANGII is approximately 10-fold greater than maternal, partially reflecting the extensive capacity of ANG II removal by the placental circulation. Contrary to previous conclusions, fetal-maternal pressor sensitivity to ANG II does not differ, whereas the placental vasculature is more sensitive to ANG II than the uteroplacental circulation. PMID- 7864100 TI - Forearm muscle insulin resistance during hypoglycemia: role of adrenergic mechanisms and hypoglycemia per se. AB - The forearm perfusion technique was used 1) to quantify the muscle metabolism of glucose and gluconeogenic precursors in response to insulin-induced hypoglycemia and 2) to assess the role of catecholamines and glucose concentration, pe se. Insulin (0.5 mU.kg-1.min-1) was infused for 4 h in three groups of healthy volunteers. In group I (n = 6), blood glucose (BG) was maintained at its basal level (4.5 +/- 0.1 mmol/l). In group II (n = 7), BG was allowed to fall to approximately 3 mmol/l. Group III (n = 6) was similar to group II except that propranolol was infused also. In addition, at 240 min, hypoglycemia was locally corrected by intrabrachial glucose infusion while maintaining the systemic milieu unperturbed. In group I, forearm glucose uptake (FGU) increased from 4.7 +/- 1.3 to a mean value of 37.8 +/- 5.0 mumol.l-1.min-1, whereas in group II it remained unchanged (8.3 +/- 2.0 mumol.l-1.min-1). In group III, propranolol partially prevented the suppression of FGU that increased to 21.6 +/- 5.2 mumol.l-1.min-1 (P < 0.05 vs. group II). Local correction of hypoglycemia normalized the FGU response (36.5 +/- 8.0 mumol.l-1.min-1). Muscle release of lactate, but not of alanine, was slightly higher during hypoglycemia (P = not significant). Forearm blood flow remained unchanged in groups I and III, whereas it increased by approximately 40% in group II (P < 0.05). It is concluded that, during mild hypoglycemia 1) extreme insulin resistance develops in the skeletal muscle, mediated by beta-adrenergic stimulation and reduced glucose mass effect and 2) mobilization of gluconeogenic precursors is only weakly activated. PMID- 7864101 TI - Differential effects of interleukin-1 receptor antagonist in cytokine- and endotoxin-treated rats. AB - Previous studies have demonstrated that the administration of the cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF)(20 micrograms/kg) to rats in a fasting state can produce many and perhaps most of the metabolic alterations found in patients with sepsis and injury. The purposes of the present study were 1) to define the metabolic effects of IL-1 and TNF during a fed state provided by continuous intravenous feeding for 20 h and 2) to characterize the unique effects of IL-1 among the overall response to cytokines by using IL-1 receptor antagonist (IL-1RA; 5 mg/kg). The effects were also explored during the endotoxemic condition induced by infusion of 200 micrograms/kg of endotoxin into rats. The results showed that during feeding IL-1 is responsible for the increase in glucose flux and plasma insulin, the development of insulin resistance, and plasma zinc depression during condition mimicking sepsis and injury, similar to effects observed in the fasting state. The changes in energy expenditure have a more complex mechanism. The results also suggested that certain host responses to cytokines or endotoxin, particularly related to protein metabolism, differed between the fed and fasting states. These data may have a special clinical relevance for the insulin-resistant state that develops during severe infection, since using IL-1RA in conjunction with nutritional therapy may offer additional advantages in the treatment of these severe metabolic disorders. PMID- 7864102 TI - Regulation of growth hormone expression in fetal rat pituitary gland by thyroid or glucocorticoid hormone. AB - The regulation of growth hormone (GH) cell development by thyroid and glucocorticoid hormones in the fetal rat pituitary gland was examined. Dexamethasone (Dex) treatment of dams induced GH and GH mRNA accumulation in the fetal pituitary gland on day 17 or 18 of gestation when substantial GH expression has not yet occurred in the control fetus. The additional thyroxine injections apparently enhanced the effect of Dex, whereas it exhibited no effect when given alone. The reduction of fetal thyroid hormone level by methimazole suppressed either the Dex induction of GH expression on day 18 or the spontaneous onset of GH expression on day 19 of gestation. The results suggest that 1) thyroid hormone exerts its stimulatory action on fetal GH gene expression only in the presence of glucocorticoid, 2) this synergistic action of these two hormones is evident as early as day 17 of gestation, and 3) rapid maturation of GH cells seen on day 19 in the normal fetus is considered to be induced by concomitant increase in both serum thyroid and glucocorticoid hormone levels. PMID- 7864103 TI - Effect of growth hormone and resistance exercise on muscle growth and strength in older men. AB - The purpose of this study was to determine whether growth hormone (GH) administration enhances the muscle protein anabolism associated with heavy resistance exercise training in older men. Twenty-three healthy, sedentary men (67 +/- 1 yr) with low serum insulin-like growth factor I levels followed a 16-wk progressive resistance exercise program (75-90% max strength, 4 days/wk) after random assignment to either a GH (12.5-24 micrograms.kg-1.day-1; n = 8) or placebo (n = 15) group. Fat-free mass (FFM) and total body water increased more in the GH group. Whole body protein synthesis and breakdown rates increased in the GH group after treatment. However, increments in vastus lateralis muscle protein synthesis rate, urinary creatinine excretion, and training-specific isotonic and isokinetic muscle strength were similar in both groups, while 24-h urinary 3-methylhistidine excretion was unchanged after treatment. These observations suggest that resistance exercise training improved muscle strength and anabolism in older men, but these improvements were not enhanced when exercise was combined with daily GH administration. The greater increase in FFM with GH treatment may have been due to an increase in noncontractile protein and fluid retention. PMID- 7864104 TI - Increased muscle carnitine palmitoyltransferase II mRNA after increased contractile activity. AB - The capacity of skeletal muscle to oxidize fatty acids increases with endurance training. The oxidation of long-chain fatty acids occurs in mitochondria and is initiated by a carnitine-dependent transport step in which three enzymes help fatty acyl groups enter the matrix compartment. The purpose of this study was to determine whether pretranslational regulation of one of these three enzymes, carnitine palmitoyltransferase II (CPT II), as estimated from the level of CPT II mRNA, plays a role in the doubling of CPT activity in skeletal muscle of rats subjected to daily 2-h bouts of running on treadmills (P. A. Mole, L. B. Oscai, and J. O. Holloszy. J. Clin. Invest. 50: 2323-2330, 1971). After 100 min/day of running on motor-driven treadmills for 2 wk, CPT II mRNA in the plantaris muscle was unchanged when normalized per unit of extracted RNA but was 50% higher (P < 0.05) over sedentary controls when normalized per unit of muscle wet weight. To test whether additional contractile activity would make CPT II mRNA even higher, continuous indirect electrical stimulation was imposed on the tibialis anterior muscles. After 9 days of chronic stimulation, CPT II mRNA was 63, 221, and 137% greater than control (P < 0.001) when normalized to extracted RNA, muscle wet weight, and whole muscle, respectively, compared with the muscle in the control rats. These data indicate that pretranslational regulation of CPT II occurs in response to increased contractile activity in skeletal muscle. PMID- 7864105 TI - Slow and fast oscillations of cytoplasmic Ca2+ in pancreatic islets correspond to pulsatile insulin release. AB - Cytoplasmic Ca2+ concentration ([Ca2+]i) and insulin secretion were monitored in single ob/ob mouse pancreatic islets stimulated by glucose. After culture in 5.5 mM of the sugar, islets responded to 11 mM glucose with pulsatile insulin secretion synchronized with oscillations of [Ca2+]i (0.3-0.5/min). Most islets also showed superimposed regular rapid [Ca2+]i oscillations and insulin transients of similar frequency. Whereas the amplitude of the slow insulin pulses increased in 20 mM glucose, the [Ca2+]i oscillations were replaced by a sustained increase. After culture in the absence of sugar, there was little rise of [Ca2+]i during exposure to 11 mM glucose and only a slight secretory response, which, however, was pulsatile. The slow secretory pulses in the presence of 11 mM glucose were augmented after culture in 11 or 20 mM glucose despite a sustained elevation of [Ca2+]i. Although pulsatile insulin release was not always associated with [Ca2+]i oscillations, the data indicate that the slow and fast [Ca2+]i oscillations do correspond to pulsatile insulin secretion. PMID- 7864106 TI - Metabolism of alpha-ketoisocaproic acid in isolated perfused liver of cirrhotic rats. AB - To determine the hepatic fate of alpha-ketoisocaproate (KIC) in cirrhosis, six groups of isolated rat livers were perfused with 0, 0.5, 1 (with or without alpha [1-14C]KIC), 2, and 5 mM KIC; control livers from healthy rats were studied in parallel under similar conditions. KIC was rapidly removed by the normal livers, whereas uptake was lower in the cirrhotic livers at all concentrations tested (at 2 mM, 4.04 +/- 0.33 vs. 6.32 +/- 0.58 mumol/min; P < or = 0.05). The transamination pathway, evaluated by leucine exchanges, was more important in the cirrhotic livers (25.4 vs. 6.8% in controls at 2 mM). The incorporation of alpha [1-14C]KIC in proteins of cirrhotic liver was increased compared with controls (0.25 +/- 0.04% of alpha-[1-14C]KIC was incorporated in proteins excreted in perfusate vs. 0.20 +/- 0.04 in controls; P < or = 0.05). In addition, a line of evidence suggests that glutamine rather than glutamate is the N donor for leucine synthesis from KIC. The decarboxylation pathway evaluated by beta-hydroxybutyrate production and by 14CO2 release from alpha-[1-14C]KIC was reduced, respectively, by 40-85% (according to KIC dose) and by 24% at 90 min in cirrhotic livers compared with healthy livers. These results indicate a dramatic modification of KIC metabolism in the cirrhotic liver; its uptake by the liver is decreased and its incorporation into proteins is increased via an enhancement of transamination to leucine, probably as a consequence of an inhibition of branched-chain keto acid dehydrogenase. PMID- 7864107 TI - Inhibition of insulin-mediated glucose uptake in rat hindlimb by an alpha adrenergic vascular effect. AB - The vasoconstrictor norepinephrine, at high doses, inhibits oxygen uptake (VO2) in the perfused hindlimb, possibly by opening vascular shunts and reducing nutrient access. Thus, in the present study, the effect of norepinephrine on insulin-mediated glucose uptake (IMGU) was assessed. Rat hindlimbs were perfused at constant flow with medium containing 8.3 mM glucose and a tracer amount of 2 deoxy-D-[1-3H]glucose (2-DG) with and without 15 nM insulin, 10 microM norepinephrine (NE), and combinations of the adrenergic blockers propranolol (Prop) and prazosin. Perfusions were also conducted at a lower dose of 1 microM NE where VO2 is stimulated. NE (10 microM) inhibited IMGU > 80%, and this inhibition, when measured by 2-DG uptake, was most pronounced in muscles rich in white fibers. The inhibitory effect of NE on IMGU comprised a beta-adrenergic component also partly evident at lower concentrations of NE (i.e., 1 microM) and an alpha-adrenergic component only evident at 10 microM NE. In contrast to the results for the hindlimb, 10 microM NE plus Prop (alpha-adrenergic combination) had no significant effect on insulin-mediated 2-DG uptake by isolated incubated soleus or extensor digitorum longus muscles. It is concluded that NE, at doses likely to occur at sympathetic vasoconstrictor synapses in muscle, impairs IMGU by a vascular effect to cause shunting and reduce access. PMID- 7864108 TI - Regulation of mineral homeostasis in osteopetrotic (op) rats. AB - The osteopetrotic (op) rat is a lethal mutation characterized by severe skeletal sclerosis resulting from reduced bone resorption. Although the skeletal manifestations have been studied extensively, little is known about mineral homeostasis in this mutation. This paucity of data prompted us to undertake this study quantitating circulating levels of calcium, phosphorus, 1,25 dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) in op mutants and normal rats between 2 and 8 wk of age. Calcium and phosphorus levels were significantly lower in op mutants at younger ages; both parameters normalized by 6 wk. Serum levels of 1,25(OH)2D were markedly elevated in op rats at all ages and showed no signs of normalization. Serum PTH levels were also elevated at most ages, with the greatest increase occurring when op mutants were severely hypocalcemic. These results demonstrate that, in op mutants, changes in circulating PTH and calcium levels were interdependent; however, levels of 1,25(OH)2D did not change despite normalization of serum calcium and phosphorus. The latter deserves further investigation and supports the hypothesis of a localized (skeletal) resistance to 1,25(OH)2D. PMID- 7864109 TI - Increased insulin-like growth factor I mRNA expression in rat osteocytes in response to mechanical stimulation. AB - We recently developed an experimental model whereby a single 10-min episode of mechanical stimulation induces bone formation in the eighth caudal vertebra of 13 wk-old rats. We used this model to relate the kinetics of the bone-forming response, as measured by administration of fluorescent markers, to an in situ hybridization analysis of changes in mRNA for two matrix proteins (type I collagen and osteocalcin) and a growth factor implicated in the regulation of bone formation [insulin-like growth factor I (IGF-I). We found that increased fluorochrome labeling was accompanied by an increase in the proportion of trabecular bone surfaces on which transcripts for collagen type I and osteocalcin were detectable, from < 3 to 25% 72 h after loading. IGF-I expression on trabecular surfaces showed a slightly earlier increase. We also noted intense hybridization for IGF-I in osteocytes in the diaphyseal cortex and in metaphyseal trabeculae. This was observed only in loaded bones, within 6 h of loading, and became undetectable in trabecular osteocytes 48 h and cortical osteocytes 120 h after loading. This is the first identification of a specific mRNA species in osteocytes after mechanical stimulation. Its production before the increase in transcription of matrix protein mRNA, and before the transcription of IGF-I mRNA in bone surface cells, represents persuasive evidence for a role for osteocytes, and for IGF-I, in the osteogenic response of bone to mechanical stimulation. PMID- 7864110 TI - Altered response of protein synthesis to nutritional state and endurance training in old rats. AB - This study was undertaken to determine whether the loss of muscle protein mass during aging could be explained by a reduced sensitivity of muscle protein synthesis to feeding and exercise. Male Wistar rats aged 12 and 24 mo were exercised by treadmill running for 4 mo. Protein synthesis was measured by the flooding dose method in tibialis anterior, soleus, and liver of conscious rested, trained rats and age-matched controls in the postprandial or in the postabsorptive state. No marked change with age could be detected in basal muscle protein synthesis. In contrast, protein synthesis was stimulated in adult but not in old rats by feeding in tibialis anterior and by exercise in soleus. In liver, protein synthesis was not modified by age but was stimulated by feeding and by exercise, which improved the response to feeding. We conclude that the impact of nutrition on muscle protein synthesis is blunted in old age, which could contribute to the age-related loss of nutrition-sensitive muscle proteins. PMID- 7864111 TI - Oxotremorine-m potentiation of glucose-induced insulin release from rat islets involves M3 muscarinic receptors. AB - cDNAs encoding for M1 and M3 muscarinic acetylcholine (ACh) receptors were detected in rat pancreatic islet cells by polymerase chain reaction (PCR) amplification techniques. A new cholinergic agonist, oxotremorine-m (oxo-m), in the presence of glucose (5.6 mM), produced a dose-dependent potentiation of insulin secretion saturating at approximately 5 microM. This effect was suppressed by the L-type Ca2+ channel blocker nifedipine. Higher doses of oxo-m (50 microM) induced a biphasic insulin response both at low (5.6 mM) or high (16.7 mM) glucose concentrations. In a Ca(2+)-deficient medium containing glucose (5.6 mM), oxo-m evoked only a reduced first phase of insulin secretion. The potentiating effects of oxo-m were inhibited by the muscarinic receptor antagonists 4-diphenylacetoxy-N-methylpiperidine methiodide (M3), hexahydro-sila difenidol hydrochloride, p-fluoro analogue (M3 > M1 > M2), and pirenzepine (M1) in a dose-dependent manner; half-maximal inhibitory concentration values were approximately 5, 20, and 340 nM, respectively. The PCR results demonstrate the presence of M1 and M3 muscarinic ACh receptors in the islet tissue, and the secretion data strongly suggest that the potentiation of glucose-induced insulin release evoked by oxo-m depends on the activation of a muscarinic M3-subtype receptor present in the beta-cell membrane. PMID- 7864112 TI - Somatostatin receptor-effector system in rat pancreatic acinar membranes after subtotal enterectomy. AB - In the present study we found that exocrine pancreatic hyperplasia observed after proximal small bowel resection is accompanied by an increase in pancreatic somatostatin (SS) content at 1 mo and an increase in the number of SS receptors at 2 wk and 1 mo after intestinal surgery. At 6 mo after small bowel resection SS content and SS receptors had returned to control values. However, the original increase in SS receptor number was accompanied by a decrease in the ability of SS to inhibit forskolin-stimulated adenylyl cyclase (AC) activity. In addition, the ability of 5'-guanylylimidodiphosphate (a nonhydrolyzable GTP analogue) to inhibit SS receptor binding was decreased in pancreatic acinar membranes from enterectomized rats at 2 wk and 1 mo after jejunoileal resection. These data suggest that there is an abnormality in the integrity of SS receptor binding site G protein interactions and would explain the decreased inactivation of AC by SS at 2 wk and 1 mo after proximal small bowel resection. PMID- 7864113 TI - Amazing pancreas: specific regulation of pancreatic secretion of individual digestive enzymes in rats. AB - We investigated the effects of somatostatin (SMS)-201-995, atropine, and MK-329 on the role of cholinergic- and cholecystokinin-related systems and on the secretory relationship between five pancreatic digestive enzymes in rats. Animals kept in restraint cages and provided with pancreatic, biliary, duodenal, and jugular vein cannulas were treated as follows: 1) 0.25 micrograms.kg-1.h-1 caerulein alone, 2) both 0.25 micrograms.kg-1.h-1 caerulein and 100 micrograms.kg 1.h-1 atropine, 3) both caerulein and 5 micrograms.kg-1.h-1 SMS, 4) 91.3 micrograms.kg-1.h-1 carbachol alone, 5) both carbachol and 0.5 mg.kg-1.h-1 MK 329, and 6) both carbachol and 5 micrograms.kg-1.h-1 SMS, respectively. Food, but not water, was denied rats starting 10 h before the experiment and throughout the 6-h experimental period. The secretory patterns over the 6-h experimental period showed noticeably independent regulation of pancreatic secretion of individual digestive enzymes. The relationship between paired enzymes significantly varied according to the treatment. The correlation between chymotrypsinogen and the other enzymes was markedly modulated by MK-329. Our results suggest that SMS is a major "gate-keeper" in the regulation of exocrine pancreatic secretion and that the secretion of each digestive enzyme is individually regulated. Furthermore, they suggest that cholecystokinin and acetylcholine and their respective agonists are essentially initiators of secretory processes of the pancreas. Therefore, the paradigms of the regulation of pancreatic secretion heretofore accepted should be reexamined. PMID- 7864114 TI - Plasma arginine, citrulline, and ornithine kinetics in adults, with observations on nitric oxide synthesis. AB - The plasma fluxes of ornithine (Orn), arginine (Arg), and citrulline (Cit) and rate of conversion of labeled ornithine-to-citrulline (QOrn-->Cit) were estimated in six healthy adult men receiving an arginine-rich or arginine-free L-amino acid based diet, each for 6 days. On day 7 an 8-h (3-h fast, 5-h fed) primed continuous intravenous infusion of L-[guanido-15N,15N] arginine, L-[ureido 13C]citrulline, L-[5,5,2H2]ornithine, and L-[5,5,5-2H3]leucine was conducted. Mean citrulline fluxes (mumol.kg-1.h-1) were 10.4-13.6 for the various conditions and/or diets and remained unchanged (P > 0.05). Arginine flux was lowered (P < 0.01) by 38% for fed state during arginine-free period. Ornithine fluxes for arginine-rich were (P < 0.01) reduced with the arginine-free diet. Rates of QOrn- >Cit declined by 30% (P < .05) during the fed arginine-free period. Short-term restriction in the dietary supply of arginine did not alter the rate of whole body nitric oxide synthesis. One subject showed a very high output of nitrate on arginine-free diet (6 times average for remaining subjects). PMID- 7864115 TI - Effect of protein malnutrition on neutral amino acid transport by rat hepatocytes during development. AB - Hepatocytes from suckling rats whose mothers were fed a low-protein diet (9% protein) showed a lower capacity for Na(+)-dependent L-alanine uptake [due to a decrease in maximal uptake rate (Vmax) of a low-affinity component of transport] and were not able to respond to insulin or glucagon, whereas those from suckling pups whose mothers were fed the control diet (17% protein) had already developed the ability to upregulate L-alanine transport after hormone treatment. When animals from low-protein-fed mothers were weaned onto a hypoprotein diet, the overall capacity for Na(+)-dependent L-alanine uptake (apparent Vmax) and its responsiveness to pancreatic hormones were restored. Hepatocytes from these animals showed a lower response to glucocorticoid treatment. Amino acid availability was dramatically decreased in suckling and weanling rats fed a low protein diet. These results support the hypothesis that nutrient supply is an important factor in the proper development of hepatic transport functions during the suckling-weaning transition. PMID- 7864116 TI - Intralobular zonal heterogeneity and hepatic indicator dilution curves. AB - Conventional interpretation of hepatic indicator dilution curves rests on the assumption, among others, that every hepatocyte operates with the same rate constants. When this assumption is false, owing to intralobular zonal variation in surface-to-volume ratios and/or to zonal differences in permeability, the apparent rate constants recoverable from outflow transients are wrong estimates of average liver performance. We develop the theoretical basis for this conclusion and illustrate by example how it can confuse the interpretation of experimental data. The analysis proceeds from vascular and extracellular reference curves recorded from perfused rat livers and from a simple model of intralobular architecture in which highly arborized periportal sinusoids have a larger surface-to-volume ratio than the less-branched vasculature around the central vein. The experimental data and the model, applied to a wide range of hypothetical solutes, are used to compare the true average rate constants for uptake, efflux, and intracellular removal with the apparent values recoverable from outflow curves. When zonal differences in surface-to-volume ratios are the sole source of heterogeneity, the wrong estimates prove of little practical importance. By contrast, assigning larger regional variations in permeability leads to substantial errors. The confusion arising from such errors may be qualitative as well as quantitative. The presence of heterogeneity and thus the risk of interpretive error appears unrecognizable from outflow curves. PMID- 7864117 TI - Luminal dilution caused by certain mild irritants and capsaicin contributes to their gastric mucosal protection. AB - We have recently shown that certain mild irritants caused the increase in fluid volume in the rat stomach. The present study was conducted to investigate 1) whether standing fluid in the gastric cavity can prevent gastric mucosal injury caused by 0.6 N HCl and 2) the mechanisms by which certain mild irritants increase the gastric fluid volume. One milliliter of water administered immediately before irritants greatly inhibited gastric lesion formation. Sodium chloride and capsaicin induced a profound enhancement of gastric fluid volume, as acid mild irritants did also. Sensory denervation completely abolished the volume increase caused by capsaicin but hardly influenced that caused by mild irritants. Capsaicin increased the amount of Evans blue in the gastric fluid, but mild irritants did not. On the other hand, HCl and capsaicin significantly inhibited the emptying of phenol red. From these results, we conclude that mild irritants and capsaicin can induce volume increase that by itself is enough to afford protection through luminal dilution. Capsaicin but not mild irritants requires sensory neurons to increase the gastric fluid volume. Certain mild irritants may provide a fluid pooling effect partly by inhibiting gastric emptying. PMID- 7864118 TI - Solubilization of receptors for pancreatic polypeptide from rat liver membranes. AB - We have previously identified, on rat liver microsomes and plasma membranes, proteins that bind pancreatic polypeptide (PP) with high affinity and specificity and that may serve as receptors for a hepatic effect of PP (J. Biol. Chem. 267: 9416-9421, 1992). Further characterization of these proteins requires the solubilization of receptors with conserved ability to bind PP selectively and efficiently. In this report, using 6 mM of the zwitterionic detergent 3-[(3 cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS), we solubilized, from liver microsomes, receptors that bound PP with high affinity (dissociation constant 6.15 +/- 1.6 nM) and specificity (no interaction with the homologous peptides neuropeptide Y and peptide YY). Gel filtration chromatography showed different degrees of receptor aggregation related to different concentrations of CHAPS in the eluent. To characterize the structure of these solubilized receptors, the chemical cross-linker N-(5-azido-2-nitrobenzoyloxy)succinimide was used to covalently bind these receptors to radiolabeled PP, and the resulting PP receptor complexes were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A radioactive band with an apparent molecular weight (M(r)) of 46,000 was detected that was inhibited by unlabeled PP with a half-maximal inhibitory concentration of approximately 10(-8) M. It most likely reflected a PP receptor with an estimated M(r) of 42,000, excluding the molecular weight of PP. The migration of this complex was not affected by the reducing agent dithiothreitol, suggesting the absence of disulfide bonding. The solubilization and identification of a bioactive hepatic PP receptor will allow further characterization and purification of this receptor and will lead to the clarification of the interaction between PP and the digestive system. PMID- 7864119 TI - Vitamin A trafficking in Caco-2 cells stably transfected with cellular retinol binding proteins. AB - During intestinal vitamin A absorption, retinol is esterified by long-chain fatty acids and secreted in chylomicron particles. Stable transfectants of the human intestinal Caco-2 cell line overexpressing cellular retinol binding protein II (CRBP II) or coexpressing CRBP II and CRBP were established to study their role in intestinal vitamin A trafficking. Compared with control cell lines, retinol uptake increased up to twofold by overexpression of CRBP II and up to 2.9-fold by coexpression of CRBP and CRBP II. Retinyl ester synthesis was increased proportionate to the increase in retinol absorption in all cell lines. Retinyl ester secretion was directly correlated with retinyl ester synthesis in control and CRBP II-transfected cell lines. However, transfection with CRBP increased the proportion secreted. Expression of CRBP and CRBP II also affected the polarity of retinyl ester secretion by increasing the proportion secreted basolaterally. Thus these studies provide evidence that intestinal retinol uptake, retinyl ester synthesis, and retinyl ester secretion are correlated with levels of CRBP and CRBP II and that the effects of CRBP on retinyl ester secretion can be distinguished from those of CRBP II. PMID- 7864120 TI - Physiology of oropharyngeal swallow in the cat: a videofluoroscopic and electromyographic study. AB - The majority of animal studies of deglutition have examined electrically stimulated swallows in sedated animals. This present investigation examined oropharyngeal and cervical esophageal swallow physiology in three awake normal domestic cats using concurrent electromyography (EMG) and videofluorography (VFG). Hooked wire electrodes were surgically implanted into six oropharyngeal muscles in each cat. During collection of VFG and EMG data, each cat ate barium impregnated cat food while the fluorography tube focused on a lateral view of the oral cavity, pharynx, and cervical esophagus. A number of significant differences in the physiology of swallowing were found between the cat and human adult. The oral stage of swallow is much longer in the cat with bolus accumulation in the valleculae. Duration and components of the pharyngeal stage of swallow are much faster, and the pharyngeal stage occurs earlier in relation to bolus passage through the cricopharyngeus. In addition, the cat exhibits a marked superior constrictor bulge at the onset of the pharyngeal contractile wave and summation of the peristaltic waves in the esophagus, whereas the human adult does not. Feline swallow physiology is more similar to that of the human infant than that of human adults. PMID- 7864121 TI - Lovastatin induces synthesis of cholesterol, which acts as a secretagogue of biliary phospholipids in rats. AB - The effects of treatment with lovastatin (LS), a hypocholesterolemic drug, on hepatic metabolism of cholesterol (CH) and phosphatidylcholine (PC) were studied in rats. Hepatic synthesis of CH was increased, as previously reported by our laboratory. Total plasma CH was increased, and biliary secretion of CH was raised fourfold, but biliary secretion of bile salts was not affected. Because CH is practically insoluble in an aqueous milieu, we tested the hypothesis that excessive CH is solubilized and secreted into bile as cholesterol-phospholipid (CH-PL) vesicles. The effects of LS-induced increase in CH synthesis on hepatic metabolism of PC after 7 days of oral LS treatment (17.5 mg/day) were studied. Our results showed accelerated synthesis of PC and increased biliary secretion of newly formed PC into bile, as evidenced by the following. 1) Phosphocholine cytidylyltransferase (EC 2.7.7.15) activity, the rate limiting enzyme in the synthesis of PC, increased 2.5-fold in the hepatic microsomes of the hepatocytes. 2) After intravenous administration of [14C]choline, a precursor of PC, [14C]PC increased significantly in bile. 3) Biliary output of PC increased twofold. 4) Quasi-elastic light scattering measurements of bile showed a 3.5-fold increase in intensity of the CH-PL vesicles, indicating higher concentrations of CH-PL vesicles, but there was no change in the intensity of the micelles. These observations support the hypothesis that PC synthesis was enhanced as a transport mechanism for secretion of the excessive amounts of cholesterol from the hepatocytes into bile as CH-PC vesicles. PMID- 7864122 TI - Stability of circadian and minor cycles of exocrine pancreatic secretion in atropine- and MK-329-infused rats. AB - We previously demonstrated the existence of a circadian rhythm of pancreatic secretion of fluid and digestive enzymes, which was superimposed on by a regular 1.84-h minor cycle of exocrine pancreatic secretion of fluid and total protein, amylase, and chymotrypsinogen (25). Direct control of these daily and hourly rhythms of pancreatic secretory function has not been addressed. Cholinergic and cholecystokinin (CCK)-associated influences on these two rhythms of exocrine pancreatic secretion were investigated in rats provided with pancreatic, biliary, duodenal, and jugular vein cannulas, allowing separate drainage of bile and pure pancreatic juice, as well as intravenous infusions of atropine sulfate and/or MK 329. Rats were kept in restraint cages under controlled temperature and humidity, with a regular 12-h light cycle, and divided into five groups. The first group of fed rats was constantly infused with 200 micrograms.kg-1.h-1 atropine, the second with 0.5 mg.kg-1.h-1 MK-329, and the third with both. In the group where both drugs were simultaneously infused, 500 micrograms.kg-1.h-1 atropine was intraperitoneally administered, whereas MK-329 was infused by intravenous cannula. Two groups consisted of fasted rats, of which one was also given atropine (100 micrograms.kg-1.h-1). Three-day experiments were performed separately with fed rats, and 2-day experiments were performed with fasted rats; atropine and/or MK-329 infusion, starting on day 2, was constant over 48 h in both fed and fasted rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864123 TI - Hemileaflet susceptibility to oxidative damage in the intestinal brush-border membrane. AB - Oxidation of biological membranes is characteristic of many types of tissue injury, including those observed with inflammatory bowel disease. The lipid compositions of the inner and outer leaflets of biological membranes differ significantly, making one leaflet theoretically more susceptible to oxidative stress than the other. In this study, we evaluated the susceptibility of each membrane hemileaflet for peroxyl radical-mediated oxidation. In vitro peroxidation of intestinal brush-border membrane was initiated with the peroxyl radical-generator 2,2'-azobis-(2-amidinopropane)hydrochloric acid (AAPH). Oxidation events were monitored by following the oxidation-sensitive degradation of the lipid-soluble fluorescent probe cis-parinaric acid (PnA). The degradation patterns were clearly distinct in the inner and outer hemileaflet. PnA degradation in the inner hemileaflet was consistent with a slow first-order reaction, whereas degradation in the outer leaflet appeared as two first-order processes delayed in time. The results suggest that the sum of available antioxidants and endogenous substrates for oxidation are consumed more rapidly in the outer membrane hemileaflet, making this leaflet more susceptible to peroxidation compared with the cytofacial leaflet. PMID- 7864124 TI - Characterization of PGE2 receptors in isolated rabbit colonic crypt cells. AB - The physiological effects of prostaglandins (PG) are mediated through their interactions with specific receptors on effector cells. In this study the properties of PGE2 receptors in the rabbit distal colon were examined. We report the presence of specific, saturable, and high-affinity binding sites of PGE2 of the EP2 subtype in isolated colonic crypts. Scatchard analysis revealed the presence of two binding sites with dissociation constants of 0.3 and 10.8 nM and corresponding maximum number of receptors of 15 and 134 fmol/10(6) cells. From competition experiments in the presence of guanosine 5'-O-(3-thiotriphosphate), PGE2 binding was decreased, suggesting that the receptor is coupled to a G protein. No PGE2 binding sites were detected in surface cells. Levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured in isolated epithelial cells after being exposed to different concentrations of PGE2. cAMP levels were significantly increased only in the crypt cells when exposed to PGE2. These data provide the first demonstration for the existence of PGE2 receptors on colonic crypt cells, which when activated lead to increased levels of cAMP. PMID- 7864125 TI - Role of vagal and splanchnic capsaicin-sensitive afferents in enterogastric inhibition of acid secretion in rats. AB - The role of capsaicin-sensitive afferent innervation and neural pathways involved in the enterogastric inhibition of gastric acid secretion by luminal acid was investigated in urethan-anesthetized rats. Intestinal perfusion with graded concentrations of HCl (50, 75, and 100 mM) for 1 h dose dependently inhibited both thyrotropin-releasing hormone (TRH) analogue- and pentagastrin-stimulated acid output (P < 0.01). The inhibitory effect of intestinal perfusion with HCl (100 mM) on pentagastrin-stimulated acid secretion was blocked by bilateral vagotomy, whereas celiac ganglionectomy had no effect. Systemic capsaicin pretreatment (125 mg/kg sc) reduced the antisecretory effects of luminal acid on both TRH analogue- and pentagastrin-stimulated acid secretion. Neither selective perivagal nor selective periceliac capsaicin treatments (1% solution) modified the antisecretory effect of intestinal perfusion with HCl (75 mM) on TRH analogue stimulated acid secretion. However, combined selective perivagal plus periceliac capsaicin treatment reduced it to the same extent as systemic capsaicin treatment. We conclude that enterogastric inhibition of acid secretion by luminal acid in urethan-anesthetized rats is mediated by extrinsic reflexes involving both vagal and splanchnic capsaicin-sensitive afferent fibers. PMID- 7864126 TI - Effects of 5-HT alone and its interaction with TRH on neurons in rat dorsal motor nucleus of the vagus. AB - The purpose of this study was to determine whether exposure to thyrotropin releasing hormone (TRH) enhances the excitatory effect of 5-hydroxytryptamine (5 HT) on motoneurons of the dorsal motor nucleus of the vagus (DMV) as described in whole animal studies. For this purpose we used the patch-clamp technique applied to rat brain stem slices. Exposure of DMV motoneurons to concentrations of 5-HT (0.1-3 microM) resulted in a concentration-related increase in spontaneous firing rate. As previously described by Travagli et al. [Am. J. Physiol. 263 (Gastrointest. Liver Physiol. 26): G508-G517, 1992], TRH (1-30 microM) increased action potential firing rate. Indeed, when TRH perfusion increased the firing rate, addition of 5-HT to the perfusing solution exerted no further excitation of the DMV motoneuron, indicating that there was no summation of response. Studies using whole cell current recordings showed a common action of 5-HT and TRH in antagonizing the Ca(2+)-dependent afterhyperpolarizing current (IAHP). Again, interaction studies between TRH and 5-HT indicated no enhancing effect of TRH on 5-HT-induced antagonism of IAHP. In conclusion, our data indicated that the enhancement of 5-HT-induced excitation of DMV motoneurons by TRH described by in vivo rat experiments is not due to an interaction of TRH and 5-HT directly on the DMV motoneuron. PMID- 7864127 TI - Ursodeoxycholic acid inhibits glucagon-induced cAMP formation in hamster hepatocytes: a role for PKC. AB - The effect of bile acids on adenosine 3',5'-cyclic monophosphate (cAMP) synthesis was investigated in isolated hamster hepatocytes. Bile acids had no direct effect on cAMP production. However, ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid inhibited, by approximately 45%, cAMP formation induced by concentrations of glucagon greater than 1 nM, with a respective half-maximum inhibitory effect observed at 4 +/- 2 microM. Similar inhibition was observed with phorbol 12 myristate 13-acetate (PMA). Chenodeoxycholic, murocholic, and taurodeoxycholic acids were the next most potent bile acids. Taurolithocholic acid was 100-fold less potent than UDCA, whereas both ursocholic and taurocholic acids had no effect at concentrations up to 0.5 mM. Neither bile acids nor PMA affected either the binding of glucagon to its receptor, the cAMP-dependent phosphodiesterase, adenylate cyclase, or the inhibitory and stimulatory (Gs) GTP-binding proteins. The inhibitory effect of PMA and UDCA on glucagon-induced cAMP synthesis was abolished in the presence of the protein kinase C (PKC) inhibitor, staurosporine. Furthermore, UDCA induced PKC translocation from cytosol to membrane and stimulated phosphorylation of an 80-kDa protein substrate for PKC. In conclusion, mediated by PKC activation, bile acids inhibit glucagon-induced cAMP synthesis by uncoupling the glucagon receptor and Gs. PMID- 7864128 TI - Downregulation of E. coli-induced TNF-alpha expression in perfused liver by hypoxia-reoxygenation. AB - We tested the hypothesis that reducing the hepatic O2 supply by 30 min of constant-flow hypoxia (PO2, approximately 45 Torr) following gram-negative bacteremia downregulates tumor necrosis factor-alpha (TNF-alpha) in buffer perfused rat lives (total n = 44). Eight groups were studied after intraportal 10(9) viable E. coli serotype 055:B5 (EC) or 0.9% NaCl (NS) at t = 0:1) normoxic EC; 2) normoxic NS controls; 3) EC+hypoxia (H)-reoxygenation (R) in which H began 30 min after EC followed by 120 min of R; and 4) NS+H/R. To assess the role of cyclooxygenase vs. xanthine oxidase activation, the effects of 10(-5) M indomethacin (Indo) in 5) Indo+EC+H/R and 6) Indo+NS+H/R were compared with allopurinol (Allo) in 7) Allo+EC+H/R and 8) Allo+NS+H/R groups. Bacterial clearance, bioactive and antigenic TNF-alpha, and hepatic O2 uptake and performance were serially assessed, as was prostaglandin (PG) E2 at baseline and peak hypoxia in EC-challenged groups. Intrahepatic bacterial killing and TNF alpha mRNA were determined at t = 180 min. Bioactive venous TNF-alpha did not increase in normoxic NS controls (6 +/- 3 U/ml at t = 180 min; mean +/- SE), whereas levels rose in NS4H/R by 180 min (111 +/- 34 U/ml; P < 0.01) without increases in TNF-alpha mRNA. In contrast, EC-induced increases in TNF-alpha transcripts during normoxia were attenuated in EC+H/R, as were protein levels (57 +/- 20 U/ml; P < 0.05), despite similar bacterial clearance. Neither Indo mediated reductions in PGE2 nor allopurinol increased TNF-alpha after EC+H/R.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864129 TI - The phrenic ampulla: distal esophagus or potential hiatal hernia? AB - The mechanics of phrenic ampullary emptying were analyzed to determine whether this structure functions in a manner similar to the tubular esophagus or a hiatal hernia. Simultaneous videofluoroscopy and intraluminal manometry of the gastroesophageal junction were done during barium swallows in 18 normal volunteers. Esophageal emptying was studied without any external influences, during abdominal compression with a cuff inflated to 100 mmHg, during a Muller maneuver, and after medication with atropine. The key finding of the study was that ampullary emptying was distinct from esophageal bolus transport in several ways: the propagation velocity of the clearing wave was slower, the maximal contact pressures achieved after luminal closure were lower and unaffected by atropine or outflow obstruction, and ampulary emptying was driven by a hydrostatic pressure difference between the ampulla and stomach rather than by a peristaltic contraction. Increased bolus volume slightly enlarged the ampulla. Taken together, these findings suggest that ampullary emptying occurs, in part, as a result of the restoration of esophageal length (presumably by tension from the phrenoesophageal membrane) rather than as a result of an aborally propagated contraction. As such, a normal phrenic ampulla is analogous to a small reducing hiatal hernia. We speculate that overt hernia formation occurs as a result of progressive degeneration of the phrenoesophageal membrane. PMID- 7864130 TI - Disassembly of rat pancreatic acinar cell cytoskeleton during supramaximal secretagogue stimulation. AB - In vivo stimulation of the exocrine pancreas with concentrations of secretagogue in excess of a maximally stimulating dose causes a marked disturbance of the intracellular segregation, transport, and exocytosis of digestive enzyme zymogens. Under physiological conditions elements of the cytoskeleton, most notably microtubules and microfilaments, are involved in the regulation of these intracellular events. We infused caerulein, a peptide analogue of cholecystokinin, at a supramaximal dose (10 micrograms.kg-1.h-1 for up to 6 h) intravenously in rats. To study the ultrastructural alterations of acinar cell microfilaments and microtubules by immunogold labeling, we used monoclonal antibodies directed against actin and beta-tubulin. As early as 30 min after the start of the secretagogue infusion we found a progressive disassembly of microtubules and microfilaments in exocrine cells. In immunoblot studies this disassembly of the cytoskeleton was paralleled by a degradation of its structural proteins actin and beta-tubulin. Our results indicate that the earliest morphological events during supramaximal secretagogue stimulation of the pancreas involve the disassembly and degradation of microtubules and microfilaments. This cell biological phenomenon offers an explanation for the disturbances of segregation, transport, and exocytosis of digestive enzymes, which are known to be associated with supramaximal stimulation of the pancreas and experimental models of pancreatitis. PMID- 7864131 TI - Cholestasis is associated with preproenkephalin mRNA expression in the adult rat liver. AB - Cholestatic liver disease is associated with clinical and experimental findings consistent with increased opioidergic neuromodulation, increased plasma total opioid activity, and elevated plasma enkephalin concentrations. In contrast to the normal adult rat liver, preproenkephalin mRNA was detected by Northern blotting in livers of adult rats with cholestasis due to bile duct resection and not in the sham-resected controls. Preprodynorphin mRNA was not detected in livers of either group, while preproopiomelanocortin mRNA was found in very low levels in both groups. Preproenkephalin mRNA was not expressed in the livers of rats with acute hepatocellular necrosis induced by thioacetamide. Hybridization histochemistry of cholestatic livers demonstrated the presence of preproenkephalin mRNA primarily over cells in the periportal areas, some of which appeared to be proliferating bile ductular cells. Immunohistochemical staining of cholestatic liver indicated the production of at least Met-enkephalin in association with preproenkephalin gene expression. These findings suggest that the liver itself, by synthesizing enkephalins, contributes directly to the abnormalities of the opioid system reported in cholestasis. PMID- 7864132 TI - Inhibition of gastric mechanoreceptor discharge by cholecystokinin in the rat. AB - The aim of the present study was to investigate electrophysiologically the effect of systemic cholecystokinin (CCK) on the discharge of vagal gastric mechanoreceptors. Twenty-two single vagal afferent fibers were selected for the investigation of responses to intravenous CCK octapeptide (CCK-8) on the basis of a positive response to gastric distension. Resting discharge in these afferent fibers was 1.3 +/- 0.3 impulses.s-1 and increased to 9.2 +/- 0.9 impulses.s-1 during distension (P < 0.0001), CCK (20-100 pmol iv) caused a gastric relaxation of 2.1 +/- 0.2 cmH2O and inhibition of phasic motility. The discharge of 20/22 of vagal tension receptors closely followed the magnitude and time course of the fall in pressure. Mean discharge before and after CCK (50 pmol) was 7 +/- 0.9 and 3.9 +/- 0.8 impulses.s-1, respectively (P < 0.001, n = 22). Both the pressure response and the concomitant changes in afferent discharge were abolished by L 364,718 (1.2 mg/kg iv). Only two afferent units failed to show a decrease in firing following CCK (50 pmol), and at 500 pmol the discharge of these units was augmented. In conclusion, CCK (50 pmol) has predominantly indirect effects on gastric mechanoreceptors, which decrease their firing in association with gastric relaxation. PMID- 7864133 TI - Nitric oxide dilates tight junctions and depletes ATP in cultured Caco-2BBe intestinal epithelial monolayers. AB - We tested the hypothesis that nitric oxide (NO) modulates the permeability of tight junctions in a model intestinal epithelium (Caco-2BBe monolayers). Incubation with sodium nitroprusside (SNP) resulted in time- and concentration dependent decreases in transepithelial resistance. Permeability to fluorescein sulfonic acid increased during incubation for 24 h in the presence of 1.25 mM SNP, 5 mM S-nitroso-N-acetylpenicillamine (SNAP), or 1% NO gas. SNP-induced hyperpermeability was not due to loss of cell viability, as confirmed by intact ultrastructure, unaltered lactate dehydrogenase release, and ability to recover baseline permeability. Incubation with SNP increased permeability but only minimally increased intracellular levels of guanosine 3',5'-cyclic monophosphate (cGMP). Incubation with Escherichia coli heat-stable enterotoxin greatly increased cGMP levels with only a minimal effect on permeability. Cellular ATP levels decreased after incubation with SNP, SNAP, or gaseous NO. Incubation with SNP led to diminished fluoresceinphalloidin staining of junctional actin (confocal microscopy) and widened tight junctions (electron microscopy). We conclude that NO reduces ATP levels and reversibly increases the permeability of tight junctions in cultured Caco-2BBe cells. PMID- 7864134 TI - Enteropathogenic Escherichia coli adherence to intestinal epithelial monolayers diminishes barrier function. AB - The mechanism by which enteropathogenic Escherichia coli (EPEC) causes diarrhea remains elusive. Several alterations within the host cell have been demonstrated to occur following EPEC attachment including increases in intracellular Ca2+ concentration and rearrangement and phosphorylation of several cytoskeletal proteins. The consequences of these intracellular perturbations on host cell function, however, have not been determined. The aim of this study was to examine the effect of EPEC adherence on intestinal epithelial barrier function. T84 cell monolayers were infected with either wild-type EPEC or a nonadherent isogenic derivative. Transepithelial electrical resistance, a measure of barrier function, decreased 33.5 +/- 6.4% after a 6-h incubation with the wild-type strain. Electron microscopy revealed ultrastructurally normal cells, and lactate dehydrogenase release assays failed to demonstrate cytotoxicity. Dual 22Na+ and [3H]mannitol flux studies localized the permeability defect to tight junctions. In addition, cumulative flux of the paracellular marker mannitol was four- to fivefold greater across monolayers infected with wild-type EPEC. Sequestration of intracellular calcium stores by dantrolene completely abrogated the resistance drop associated with EPEC attachment. These data demonstrate that adherence of EPEC to intestinal epithelial cell monolayers disrupts tight junction barrier function via a calcium-requiring event. PMID- 7864135 TI - Induction of liver growth in normal mice by infusion of hepatocyte growth factor/scatter factor. AB - Hepatocyte growth factor/scatter factor (HGF/SF) is a potent stimulator of DNA synthesis in a variety of epithelial cells, including hepatocytes, and has been implicated in liver regeneration. We show here that combining dextran sulfate with HGF/SF markedly increases the plasma concentrations of HGF/SF that are achieved during intraperitoneal infusion. Three days of administration of HGF/SF by this mechanism caused a dose-dependent increase in liver wet weight. Mitotic figures were rarely observed in control livers but were abundant in livers exposed to HGF/SF, and liver DNA content was elevated. Serum levels of triglycerides, cholesterol, total protein, and albumin were also dose dependently increased, whereas alkaline phosphatase was reduced. From these data we conclude 1) that combining HGF/SF with dextran sulfate provides a novel method for delivering HGF/SF in a continuous manner, 2) that HGF/SF can induce liver growth in an intact animal, and 3) that HGF/SF-induced liver enlargement is associated with changes in serum biochemistry. PMID- 7864136 TI - Inhibiting gastric H(+)-K(+)-ATPase activity by omeprazole promotes degeneration and production of parietal cells. PMID- 7864137 TI - Human SP-A: then and now. AB - In the short span of ten years, our understanding of human surfactant-associated protein A (SP-A) has advanced rapidly at both the level of the protein and the level of the gene. In the period 1984-1988, the protein was biochemically characterized and two SP-A precursors were identified. The molecular characterization was begun with the publication of an SP-A genomic sequence and sequences of two SP-A cDNAs, suggesting the presence of two SP-A genes. In the period 1991-1992, an SP-A pseudogene, a second SP-A genomic sequence, and an SP-A allelic variant were described. Since that time, a picture of increasing complexity has emerged from studies of the two SP-A genes. This complexity includes alternative splicing of 5' untranslated exons, allelic variants of both SP-A genes, and sequence heterogeneity within the 3' untranslated region. The challenge for the future will be to discover the physiological significance of the genetic complexity of human SP-A. PMID- 7864138 TI - A type I cell-specific protein is a biochemical marker of epithelial injury in a rat model of pneumonia. AB - In this study we determined whether the alveolar fluid content of a specific epithelial type I cell protein, rTI40, can be used as a biochemical marker for lung injury. A model of alveolar epithelial injury was developed by instilling Pseudomonas aeruginosa bacteria (PA103) into the airspaces of anesthetized, ventilated rats. After 6 h, the alveolar fluid content of rTI40 from PA103 treated rats was increased over 80-fold in comparison to alveolar fluid from control rats (P < 0.05). This increase in rTI40 correlated with both morphological evidence of injury to alveolar epithelial type I cells and increased permeability of the alveolar epithelium to protein tracers. In contrast, the lactate dehydrogenase activity of alveolar fluid from PA103-treated rats was elevated only threefold over control values at 6 h (P < 0.05). In a second study using a less injurious strain of P. aeruginosa (PA103 exsA::omega), the alveolar fluid content of rTI40 was the same as control values. These findings indicate that the alveolar fluid content of a type I cell-specific protein can be used as a sensitive and specific biochemical marker of type I cell injury. PMID- 7864139 TI - Volatile anesthetics inhibit voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells. AB - The relaxation of airway smooth muscle by volatile anesthetics is associated with a decreased concentration of intracellular free Ca2+. We hypothesized that inhibition of the entry of extracellular Ca2+ contributes to the relaxation. We therefore examined the effects of halothane, isoflurane, and sevoflurane on macroscopic voltage-activated Ca2+ currents (ICa) in porcine tracheal smooth muscle cells, using the whole cell patch-clamp technique. All three volatile anesthetics significantly inhibited ICa in a dose-dependent manner with no apparent shift in the voltage dependence of induced ICa. The order of inhibitory potencies for ICa was halothane > isoflurane > sevoflurane. When data were plotted as a function of the estimated anesthetic concentrations in the lipid phase, the potencies for inhibition of ICa by the three anesthetics were indistinguishable. We conclude that volatile anesthetics have an inhibitory effect on ICa of porcine tracheal smooth muscle cells at clinically relevant concentrations and that the inhibitory potencies of volatile anesthetics on ICa are closely related to their lipid-phase solubilities. PMID- 7864140 TI - Endothelin-1 synthesis, receptors, and signal transduction in alveolar epithelium: evidence for an autocrine role. AB - In the lung, endothelin-1 (ET-1) is synthesized by several cell types and acts locally to cause vasoconstriction and bronchoconstriction, activate alveolar macrophages, and stimulate chloride secretion. We report ET-1 production, binding, and signal transduction by a previously unrecognized site, the alveolar epithelial cell. L2 cells, a cloned rat alveolar epithelial cell line, secreted ET-1 and contained ET-1 mRNA. Exposure of L2 cells to lipopolysaccharide, tumor necrosis factor-alpha, interleukin-1, or transforming growth factor-beta stimulated ET-1 release, whereas interferon-gamma or platelet-derived growth factor decreased ET-1 secretion. 125I-ET-1 binding to L2 cells revealed a single binding site with a maximal binding capacity of 22.4 fmol/mg protein and a dissociation constant of 4.03 nM. 125I-ET-1 binding was completely inhibited by ET receptor A (ETA) blockade and by unlabeled ET-1 >> ET-3 = sarafotoxin 6c, consistent with the presence of ETA. Exogenous ET-1 increased, whereas blockade of endogenous ET-1 decreased prostaglandin E2 (PGE2) production by L2 cells; exogenous ET-1 also increased adenosine 3',5'-cyclic monophosphate (cAMP) production. We conclude that 1) cloned rat alveolar epithelial cells synthesize ET-1; 2) inflammatory mediators modulate ET-1 production; 3) L2 cells express ETA; 4) ET-1 increases PGE2 and cAMP levels in these cells; and 5) BQ-123, an ETA antagonist, decreases their basal PGE2 production. These studies suggest that ET 1 may function as an autocrine factor in alveolar epithelial cells. PMID- 7864141 TI - Role of intracellular pH in relaxation of porcine tracheal smooth muscle by respiratory gases. AB - Hypercapnia and hypoxia both relax airway smooth muscle, but the mechanisms responsible are poorly understood. Because hypercapnia and hypoxia can each decrease intracellular pH (pHi) and acidosis can inhibit Ca2+ channels, we hypothesized that decreased pHi mediates relaxation of trachealis muscle by each of these respiratory gases. To examine the relationship between pHi and tone, we measured isometric tension, bath pH, and fluorescence intensity (540 nm) in porcine tracheal smooth muscle strips loaded with 2',7'-bis(2-carboxyethyl)-5(6) carboxyfluorescein and excited alternately with 440- and 500-nm light. Strips equilibrated in Krebs-Henseleit solution bubbled with 95% O2-5% CO2 were contracted with carbachol and then relaxed with either 95% N2-5% CO2 or 93% O2-7% CO2. The ratio of fluorescence intensity at 500 nm to 440 nm was calibrated vs. pHi with use of nigericin. Baseline pHi was 7.19 +/- 0.03 (n = 13). Hypoxia decreased active tension by approximately 60% but did not change pHi. Hypercapnia induced decreases in tension that were associated with substantial decreases in pHi. Thus, decreased pHi does not mediate hypoxic relaxation, but the relaxation during physiologically relevant increases in CO2 concentration is associated with significant cellular acidification. PMID- 7864142 TI - Bovine herpesvirus-1 infection reduces bronchial epithelial cell migration to extracellular matrix proteins. AB - Repair of airway epithelium after viral infection involves migration of epithelial cells to cover injured, denuded areas. We determined whether viral infection reduces the capability of bronchial epithelial cells to migrate and to attach to extracellular matrix proteins. Inoculation of bovine bronchial epithelial cells in vitro with bovine herpesvirus-1 reduced their ability to migrate in two different assays of cell migration. When attachment assays were performed, fewer cells attached to both control wells and matrix protein precoated wells, suggesting that general mechanisms of adherence to substrates were altered by viral infection. Focal contact points of epithelial cells with the underlying matrix were evaluated with epifluorescence microscopy and monoclonal antibodies to vinculin and alpha v, an integrin chain. Disruption of focal contact points was seen early after infection and was prevented by an inhibitor of viral DNA polymerase, phosphonoacetic acid. Cycloheximide did not cause similar disruptions of focal contacts at early time points. Viral infection thus has marked effects on the interactions of bronchial epithelial cells with extracellular matrix and the organization of matrix to cytoskeleton links. The effects appear to be dependent in part on viral replication in the cells and are not simply due to reductions in host cell protein synthesis. PMID- 7864143 TI - Role of G proteins and KCa channels in the muscarinic and beta-adrenergic regulation of airway smooth muscle. AB - We have examined the functional consequences of G protein coupling to calcium activated potassium (KCa) channels using isometric tension records from guinea pig tracheal smooth muscle. After incubation with 1 microgram/ml pertussis toxin (PTX) for 6 h, the contraction response to 1 microM methacholine (MCh) was suppressed by 31.7 +/- 5.0% (n = 10). Similarly, the contraction was inhibited by 29.1 +/- 5.0% (n = 6) after application of 0.1 microM AF-DX 116, an M2-selective muscarinic receptor antagonist. Cholera toxin (CTX, 2.0 micrograms/ml for 6 h), which activates the stimulatory G protein of adenylyl cyclase (Gs), also suppressed contraction by 43.9 +/- 3.3% (n = 11). The inhibitory effects of PTX, AF-DX 116, or CTX were reversed in the presence of 100 nM charybdotoxin (ChTX), a selective KCa channel inhibitor. These findings suggest that disruption of inhibitory coupling between muscarinic receptor and KCa channels mediated by PTX sensitive G proteins, or KCa channel activation induced by Gs/adenylyl cyclase linked processes, antagonizes muscarinic contraction. The isoproterenol concentration-inhibition curves for precontracted trachea (1 microM MCh) were shifted to the left after perfusion with PTX or AF-DX 116, and the leftward shift of the curve was blocked by ChTX. Thus direct or indirect regulation of KCa channels mediated by the inhibitory guanine nucleotide binding protein (Gi) and Gs may play a functionally important role in the mechanical antagonism by the two receptor agonists. PMID- 7864144 TI - Insulin modulation of bronchial epithelial cell fibronectin in vitro. AB - Fibronectin (Fn) is involved in the migration of epithelial cells in re epithelialization of wounds. Epithelial cell-derived Fn is particularly potent as a chemotactic factor for bronchial epithelial cells (BECs) in vitro. Thus modulation of airway epithelial cell Fn may be a key aspect of airway repair. Insulin is both an important growth factor and known chemotactic factor for cultured BECs. We postulated that insulin may modulate Fn production of cultured BECs. We examined this hypothesis utilizing bovine BECs in culture with serum free media with and without insulin. BECs grown in media without insulin released more Fn into culture supernatants and contained more Fn in cell layers than cells grown with insulin. Labeling of cells with [35S]methionine demonstrated an increase in new protein production and Fn mRNA expression was increased. Increased Fn in BEC cultures without insulin was associated with an increase in active transforming growth factor-beta (TGF-beta) release as measured by a standard bioassay. Increased BEC Fn in cultures without insulin was partially inhibited by exposure of cultures to TGF-beta antibody. Thus insulin appears to modulate BEC Fn production in vitro in part through a TGF-beta-dependent mechanism. Insulin may be involved in airway repair mechanisms through modulation of epithelial cell Fn production. PMID- 7864145 TI - Response of cultured human pulmonary artery endothelial cells to endotoxin. AB - Endotoxemia is the leading cause of the adult respiratory distress syndrome. The effects of endotoxin on pulmonary endothelium, both in vivo and in culture, are diverse and complicated, and vary between species and cellular origin. Species such as sheep and cows are particularly sensitive to endotoxin, whereas rats and mice are more resistant. Studies using cultured pulmonary endothelial cells confirm these findings. Such species variations lead us to question whether human pulmonary artery endothelial cells (HPAEC) are directly affected by endotoxin. The present study examined the effects of endotoxin on HPAEC. Cells were exposed to endotoxin (0.001-10 micrograms/ml) for 24 h and were examined by phase contrast microscopy, and measurements were made of lactate dehydrogenase, prostacyclin, and prostaglandin E2 release in the cell-free supernatant. In the presence of serum, endotoxin doses as small as 0.01 microgram/ml resulted in endothelial retraction and pyknosis compared with controls (P < 0.05). Exposure to 10 micrograms/ml of endotoxin resulted in a significant increase in the number of pyknotic cells (P < 0.05), and lactate dehydrogenase release paralleled this finding. Endotoxin also resulted in a gradual increase in prostaglandin E2 release, reaching significance at 1 and 10 micrograms/ml of endotoxin (P < 0.05). A similar trend was noted for prostacyclin release. We conclude that the direct cytotoxic effects elicited by endotoxin on HPAEC may contribute to the onset of pulmonary edema in patients with adult respiratory distress syndrome. PMID- 7864146 TI - Respiratory nuclei share synaptic connectivity with pontine reticular regions regulating REM sleep. AB - Injection of cholinomimetics into the medial pontine reticular formation (mPRF) of intact, unanesthetized cat causes a rapid eye movement (REM) sleep-like state and respiratory depression. The mPRF contains no concentrations of respiratory neurons, and this study examined the hypothesis that respiratory depression evoked from the mPRF is synaptically mediated. The mPRF of conscious cats was injected with bethanechol to define an mPRF zone causing state-dependent respiratory depression. Bethanechol caused a 361% increase in the REM sleep-like state and a 37% decrease in minute ventilation. Additional cats were injected with the retrograde fluorescent tracers True Blue and either Fluoro-Gold or Diamidino Yellow aimed for the cholinoceptive mPRF or for the pontine respiratory group (PRG). After mPRF dye injection, 1) labeling was observed in the PRG, dorsal respiratory group (DRG), and ventral respiratory group (VRG); and 2) double-labeled cells were observed in the VRG and PRG. Dye injections into the PRG produced contralateral and ipsilateral fluorescent labeling of the mPRF, DRG, and VRG. Thus cholinoceptive regions of the mPRF involved in REM sleep generation have reciprocal monosynaptic connections with the PRG and receive monosynaptic projections from the DRG and VRG. PMID- 7864147 TI - NK1 receptors mediate leukocyte adhesion in neurogenic inflammation in the rat trachea. AB - In neurogenic inflammation, tachykinins trigger the adhesion of neutrophils and eosinophils to leaky venules. The goals of the present study were to determine whether this leukocyte adhesion is mediated by neurokinin type 1 (NK1) receptors and to determine whether the amount of leukocyte adhesion corresponds to the amount of plasma leakage. Anesthetized rats were injected intravenously with substance P, the NK1 receptor agonist [Sar9, Met(O2)11]-substance P, or the NK2 receptor agonist [beta-Ala8]neurokinin A-(4-10). Five minutes later, the adherent neutrophils and eosinophils in blood vessels of the tracheal mucosa were stained histochemically and plasma leakage was quantified, as assessed by the extravasation of Monastral blue. Substance P and the NK1 agonist caused similar amounts of leukocyte adhesion, but the NK2 agonist had no effect. Pretreatment with the NK1 receptor antagonist CP-96,345 (4 mg/kg iv), before challenge with substance P, capsaicin, or aerosol hypertonic saline, reduced the amount of neutrophil adhesion by 56%, 93%, and 57% and reduced the amount of eosinophil adhesion by 70%, 83%, and 65%, respectively. Plasma extravasation was decreased by 89%, 95%, and 94%. The number of adherent neutrophils in the trachea was strongly correlated with the number of adherent eosinophils (r2 = 0.61). The greatest amount of leukocyte adhesion occurred in larger diameter venules than did the maximal amount of Monastral blue leakage. We conclude that NK1 receptors mediate the adhesion of neutrophils and eosinophils as well as the plasma leakage triggered by substance P, capsaicin, or hypertonic saline. This leukocyte adhesion evidently does not occur at exactly the same sites as the plasma leakage. PMID- 7864148 TI - Oxidants affect permeability and repair of the cultured human tracheal epithelium. AB - To examine the effects of oxidants on the airway epithelial barrier functions, human tracheal epithelial cells were cultured on porous filter membrane. Glucose oxidase (GO; 10 U/ml), hydrogen peroxide (H2O2; 4 x 10(-3) M), and xanthine (5 x 10(-4) M) plus xanthine oxidase (20 mU/ml) (X-XO) significantly increased electrical conductance across epithelial membrane (G), short-circuit current (Isc) measured with Ussing's chamber methods, and [3H]mannitol flux through the cultured epithelium. Increases in G and Isc induced by oxidants were significantly inhibited by catalase (1,000 U/ml) and the protein kinase C inhibitor staurosporine (10(-7) M), but superoxide dismutase (SOD; 100 U/ml) was without effect. GO, H2O2, and X-XO inhibited the epithelial cell growth, [3H]thymidine incorporation by the cells, and epithelial repair of artificially produced focal epithelial defects (1-2 mm diam) on plastic vessels. Catalase also inhibited effects induced by oxidants on cell growth and proliferation. These results suggest that oxidants reduce tracheal epithelial barrier functions by damaging tight junctions and inhibiting cell proliferation, and these effects of oxidants on epithelial cells may be mediated by H2O2 rather than superoxide anion and by activation of protein kinase C. PMID- 7864149 TI - Expression and role of cyclooxygenase isoforms in alveolar and peritoneal macrophages. AB - Prostaglandin synthesis represents one means by which macrophages modulate inflammation. The initial enzyme in the metabolism of arachidonic acid to prostaglandins is cyclooxygenase (COX). Both constitutive (COX-1) and inducible (COX-2) isoforms are recognized. We previously showed that COX activity of rat peritoneal macrophages (PM) exceeds that of alveolar macrophages (AM). In this study, we correlated the steady-state levels of COX-1 and COX-2 proteins with COX activity in resident AM and PM. Freshly obtained AM contained lower levels of COX 1 than did fresh PM. Neither contained substantial amounts of COX-2 in the basal state, but both cell types demonstrated induction when cultured with lipopolysaccharide; once again, COX-2 levels in PM exceeded those in AM. Despite COX-2 induction under these circumstances, its contribution to prostaglandin production appeared to be modest. We conclude that, although both isoforms of COX are expressed in rat AM and PM, COX-1 is responsible for the majority of enzyme activity in both the basal and stimulated states. The lesser prostaglandin synthetic capacity of AM than of PM appears to be the consequence of lower steady state levels of both COX proteins. PMID- 7864150 TI - Analysis of responses to ANG IV: effects of PD-123319 and DuP-753 in the pulmonary circulation of the rat. AB - Pulmonary vasoconstrictor responses to angiotensin (ANG) IV, the 3-8 amino acid fragment of ANG II, were compared with responses to ANG I, ANG II, and ANG III and to other vasoactive peptides in the isolated blood perfused rat lung. In terms of relative activity, ANG IV was similar in potency to bradykinin and serotonin but was approximately 100-fold less potent than ANG I, ANG II, and ANG III. PD-123319, an AT2-receptor antagonist, enhanced pressor responses to the four angiotensin peptides and to bradykinin but did not significantly change the pressor response to serotonin or to ventilatory hypoxia. DuP-753, an AT1-receptor antagonist, significantly decreased pressor responses to the four angiotensin peptides and enhanced the pressor responses to bradykinin but not to serotonin. Captopril and enalaprilat increased the pressor response to ANG IV. Meclofenamate and N omega-nitro-L-arginine methyl ester shifted the dose-response curve for ANG IV to the left in a manner similar to that observed with ANG II and ANG III. These data show that ANG IV has significant vasoconstrictor activity and suggest that responses are mediated by the activation of AT1 receptors and that vasopressor responses of the angiotensin peptides may be modulated by activation of AT2 receptors. These results also suggest that responses to ANG IV are modulated by the release of vasodilator prostaglandins and nitric oxide and that AT2 receptors have little, if any, role in mediating or modulating the pressor response to ventilatory hypoxia. PMID- 7864151 TI - Ontogeny of type I procollagen expression during human fetal lung development. AB - The cellular sites of type I procollagen (PCI) production were investigated during fetal and early postnatal human lung development. PCI-synthesizing cells and sites of recent collagen deposition were visualized by immunoperoxidase staining of lung tissue with monoclonal antibodies to human PCI. In selected cases, serial sections were also examined by in situ hybridization to establish the cellular sites of PCI gene expression and mRNA accumulation. PCI cytoplasmic immunostaining generally correlated with sites of mRNA accumulation and with known sites of interstitial collagen deposition, including the adventitial and muscular layers of large blood vessels, submesothelial and peribronchial connective tissue, perichondrium, and interstitial matrix. However, we also observed developmental changes in relative PCI expression for each of these compartments, heterogeneity in the level of PCI expression by cells within individual anatomic subcompartments, and variations in the level of PCI expression along the length of pulmonary blood vessels and airways. These studies emphasize the complexity of developmentally regulated alterations in procollagen production during lung development. PMID- 7864152 TI - Endothelial cell heme oxygenase and ferritin induction in rat lung by hemoglobin in vivo. AB - Iron-derived reactive oxygen species play an important role in the pathogenesis of various vascular disorders including vasculitis, atherosclerosis, and capillary leak syndromes such as the adult respiratory distress syndrome (ARDS). We have suggested that acute incorporation of the heme moiety of hemoglobin released from red blood cells into endothelium could provide catalytically active iron to the vasculature. Adaptation to chronic heme stress involves the induction of heme oxygenase and ferritin; the latter provides cytoprotection against free radicals in vitro. The present studies examine the bioavailability of heme, derived from hemoglobin, to induce heme oxygenase and ferritin in rat lungs in vivo. Intravenous injection of methemoglobin, but not oxyhemoglobin, increases total lung heme oxygenase mRNA approximately fivefold after 16 h. Accompanying this mRNA induction, expression of total lung heme oxygenase enzyme activity is also markedly enhanced. In situ hybridization for heme oxygenase reveals mRNA accumulation in the lung microvascular endothelium, implying incorporation of heme into endothelial cells. Similarly, methemoglobin significantly increases the ferritin protein content of rat lungs and in parallel, ferritin light-chain mRNA increases approximately 1.6-fold, whereas heavy-chain mRNA is upregulated by approximately 1.9-fold. Immunoreactive ferritin is present in lung microvascular endothelium after methemoglobin treatment, suggesting incorporation of heme iron into pulmonary vasculature. Subcutaneous injection of Sn-protoporphyrin IX, a competitive inhibitor of heme oxygenase, does not affect methemoglobin-induced ferritin synthesis in lungs. We speculate that methemoglobin, which might be generated by activated leukocytes in ARDS associated with disseminated interavascular coagulation, can provide heme iron to lung microvascular endothelium to induce heme oxygenase and ferritin. PMID- 7864153 TI - Selective downregulation of ANP-clearance-receptor gene expression in lung of rats adapted to hypoxia. AB - To test the hypothesis that expression of atrial natriuretic peptide (ANP) receptor genes is modified to provide a compensatory mechanism against hypoxic pulmonary hypertension, steady state mRNA levels for the ANP-A receptor (or guanylate cyclase-A; ANPAR), ANP-B receptor (or guanylate cyclase-B; ANPBR), and ANP-clearance receptor (ANPCR) were quantitated by Northern blot and slot-blot analysis in lung, kidney, spleen, and liver of hypoxia-adapted rats and air controls. Exposure of rats to short-term (48 h) and chronic (4 wk) hypoxia (10% O2, 1 atm) did not affect lung ANPAR-mRNA levels. Lung ANPBR-mRNA levels were unchanged by short-term hypoxia but selectively increased (approximately twofold) by chronic hypoxia. ANPCR-mRNA levels were selectively and significantly downregulated by 48-h and 4-wk hypoxia in lung but were unchanged or upregulated in other tissues. Lung ANPCR gene transcription, assessed by nuclear-runoff analysis, was decreased by hypoxia. These data support the conclusion that altered pulmonary ANP-receptor gene expression modulates the development of hypoxic pulmonary hypertension. PMID- 7864154 TI - Turnover of extracellular matrix by type II pulmonary epithelial cells. AB - Rat type II pulmonary epithelial cells synthesize and assemble a multicomponent extracellular matrix (ECM) which can modulate cellular differentiation in primary culture. This study defines turnover of the type II cell matrix. Turnover kinetics were analyzed in two types of pulse-chase protocols based on loss of radioactive ECM components. To estimate turnover of previously synthesized ECM, type II cells were plated on extracted matrix that was radiolabeled 2, 3, or 6 days; alternatively, ECM was radiolabeled in pulse-chase experiments to measure turnover by the same cells that synthesized the matrix. Rapid initial rates of ECM turnover were evident in both cases. While overall matrix stability appeared to change with culture time, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed a similar spectrum of proteins in the ECM over the course of kinetic studies. The results reveal rapid turnover of ECM by type II cells and suggest that matrix stability may be regulated. These observations provide a basis for future investigations of the physiological significance of turnover of individual ECM components by the alveolar epithelium. PMID- 7864155 TI - Acid extrusion in S3 segment of rabbit proximal tubule. I. Effect of bilateral CO2/HCO3-. AB - Monitoring the absorbance spectra of the pH-sensitive dye dimethylcarboxyfluorescein, we studied intracellular pH (pHi) regulation in the isolated perfused S3 segment of rabbit proximal tubule. To explain a previous observation, that steady-state pHi is higher in the presence than in the absence of CO2/HCO3- (N. L. Nakhoul, L. K. Chen, and W. F. Boron. J. Gen. Physiol. 102: 1171-1205, 1993), we examined the effect of bilateral (i.e., luminal and basolateral) CO2/HCO3- on the acid extrusion processes responsible for recovery of pHi from acid loads. To compute fluxes from rates of pHi change, we determined the pHi dependence of intrinsic intracellular buffering power, which was approximately 50 mM/pH at pHi 6.5 and fell linearly to approximately 20 mM at pHi 7.4. In one series of experiments, we monitored the rate of pHi recovery from an acid load imposed by an NH4+/NH3 prepulse. Over a broad range of pHi values, total net acid extrusion was approximately four times higher in bilateral presence of CO2/HCO3- than in its absence. In a second group of experiments, which were designed to determine the effect of CO2/HCO3- on luminal Na+/H+ exchange, we monitored the rate of pHi recovery elicited by adding Na+ back to only the lumen, after first removing Na+ bilaterally. Initial rate of luminal Na(+)-dependent net acid extrusion in presence of CO2/HCO3- was approximately 229 microM/s (pHi 6.92), approximately 1.8 times higher than the flux of approximately 127 microM/s (P < 0.005) obtained in absence of CO2/HCO3- (pHi 6.66). CO2/HCO3- alkali-shifted the flux vs. pHi relationship by 0.3-0.4 pH units. In a final series of experiments, we examined the effect of CO2/HCO3- on the Na(+)-independent alkalinization that follows the rapid, initial acidification elicited by bilateral Na+ removal. In the presence of CO2/HCO3-, lag time for initiation of the Na(+)-independent alkalinization was only approximately 36 vs. approximately 211 s (P < 0.002) in absence of CO2/HCO3-. Also, Na(+)-independent net acid extrusion rate was approximately two to three times higher in presence than in absence of CO2/HCO3- at comparable pHi. This Na(+)-independent acid extrusion was insensitive to N-ethylmaleimide (2 mM), but was inhibited approximately 94% by efforts to deplete intracellular ATP (i.e., removal of glucose and amino acids, plus addition of 2 mM cyanide and 10 mM iodoacetic acid). Stimulation of luminal Na+/H+ exchange and Na(+)-independent acid extrusion appears to be the major, if not the entire, explanation for the higher steady-state pHi caused by bilateral addition of CO2/HCO3-. PMID- 7864156 TI - Acid extrusion in S3 segment of rabbit proximal tubule. II. Effect of basolateral CO2/HCO3-. AB - Monitoring intracellular absorbance spectra of the pH-sensitive dye dimethylcarboxyfluorescein we studied intracellular pH (pHi) regulation in the isolated perfused S3 segment of the rabbit proximal tubule. In the preceding study [Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F179-F192, 1995.], we demonstrated that simultaneously adding CO2/HCO3- to both lumen and bath stimulated two acid-extruding mechanisms, one dependent on luminal Na+ (a Na+/H+ exchanger) and one independent of Na+ (presumably a H+ pump). Here, we examine the effects of adding CO2/HCO3- to the lumen only or to the bath only. Over a broad pHi range, the total rate of pHi recovery from an acid load in the presence of Na+ was not increased by luminal CO2/HCO3-. On the other hand, basolateral CO2/HCO3- increased the pHi recovery rate to an even greater extent than had bilateral CO2/HCO3-. Regarding the Na(+)-independent pHi recovery mechanism, we found that luminal CO2/HCO3- failed to increase the pHi recovery rate compared with controls also studied in the absence of Na+. Neither did luminal CO2/HCO3- significantly affect the lag time between the maximal acid load and the initiation of the Na(+)-independent pHi recovery (approximately 147 vs. approximately 212 s in controls). On the other hand, adding CO2/HCO3- to only the bath substantially increased the rate of Na(+)-independent pHi recovery, which generally was greater than that observed with bilateral CO2/HCO3-. CO2/HCO3- only in the bath also reduced the lag time to approximately 51 s, which is not significantly different from the value of approximately 36 s observed with bilateral CO2/HCO3-. Our data are consistent with the hypothesis that basolateral (but not luminal) CO2/HCO3- stimulates both a luminal Na+/H+ exchanger and a luminal H+ pump. PMID- 7864157 TI - Stimulation of chloride transport by cAMP in rat proximal tubules. AB - We have previously demonstrated that formate and oxalate stimulate transcellular Cl- absorption (JCl) in the rat proximal tubule by a mechanism involving DIDS sensitive anion exchange across the luminal membrane and diphenylamine-2 carboxylate (DPC)-sensitive Cl- channels in the basolateral membrane. Recent evidence indicates cAMP activation of Cl- channels in apical and basolateral membranes of proximal tubule cells. We therefore tested the effect of cAMP on Cl- and fluid transport in rat proximal tubule studied by luminal and capillary microperfusion in situ. The luminal perfusate contained 5 mM HCO3- and 145 mM Cl , and the capillary perfusate contained 25 mM HCO3- and 110 mM Cl-, simulating conditions in the late proximal tubule. Addition of 0.5 mM dibutyryl cAMP markedly stimulated fluid absorption (Jv) and JCl. Similar effects resulted from addition of forskolin (10 microM) to stimulate cAMP production. The increments in Jv and JCl due to dibutyryl cAMP were abolished when the Cl- channel blocker DPC (200 microM) was added to the capillary perfusate but not when it was added to the lumen. The increments in Jv and JCl due to dibutyryl cAMP were unaffected by luminal DIDS (100 microM), which abolishes the increments in Jv and JCl induced by addition of oxalate. In contrast, the increments in Jv and JCl due to dibutyryl cAMP were abolished by luminal 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB; 10 microM), another Cl- channel blocker. Luminal NPPB had no effect on baseline Jv and JCl nor on the increments in Jv and JCl induced by addition of oxalate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864158 TI - Role of Ca2+/CaMK II in Ca(2+)-induced K+ channel inhibition in rat CCD principal cell. AB - The apical low-conductance K+ channel of rat cortical collecting duct (CCD) is inhibited by increased intracellular Ca2+ concentrations. This effect has been shown to be mediated at least in part by activation of protein kinase C (PKC). In the present study, we used the patch-clamp technique to examine the role of Ca2+/calmodulin-dependent protein kinase II (CaMK II) in mediating the Ca(2+) induced inhibitory effect. In cell-attached patches of principal cells of rat tubules, clamping of intracellular Ca2+ concentration at 400 nM by using 1 microM ionomycin reduced channel activity to 26.5% of the control value. A further reduction in channel activity, to 8.8% of the control value, was observed following the addition of phorbol 12-myristate 13-acetate (PMA), an agent known to activate PKC. Pretreatment of cells with KN-62 (CaMK II inhibitor) or GF 109203X (PKC inhibitor) attenuated the inhibitory effect of Ca2+ on K+ channel activity (83.2 and 50.7% of the control value, respectively). Even in the presence of KN-62, addition of 10 microM PMA significantly decreased channel activity to 57.2% of the control value. The Ca(2+)-induced inhibition was completely abolished by simultaneous incubation with both KN-62 and GF-109203X. In inside-out patches, addition of 20 micrograms/ml CaMK II in the presence of a PKC inhibitor reduced channel activity to 66.2% of control values. It is concluded that CaMK II is involved in mediating the Ca(2+)-induced inhibition of the activity of the apical K+ channel of rat CCD. PMID- 7864159 TI - Localization of angiotensin II type 1 receptor subtype mRNA in rat kidney. AB - The physiological effects of angiotensin II (ANG II) on the kidney are mediated primarily by the ANG II type 1 (AT1) receptor. Two highly similar AT1 receptor subtypes have been identified in the rat by molecular cloning techniques, namely AT1A and AT1B. The intrarenal localization of the AT1A and AT1B receptor subtypes has not been studied by hybridization methods with subtype-specific receptor probes. Using radiolabeled probes from the 3' noncoding region of the AT1A and AT1B cDNAs, we localized AT1 mRNA in rat kidney by in situ hybridization. Specificity of the 3' noncoding region probes was tested by Northern blot and solution hybridization methods. AT1A mRNA levels were highest in the liver, kidney, and adrenal. In contrast, AT1B mRNA levels were highest in the adrenal and pituitary and low in kidney. Autoradiographic localization of 125I [Sar1,Ile8]ANG II binding indicated that the highest levels of AT1 receptors were found in glomeruli and vascular elements. In situ hybridization with a nonselective AT1 receptor riboprobe indicated that the highest levels of AT1 mRNA were in the outer medullary vasa recta and cortical glomeruli with additional diffuse labeling of the cortex and outer medulla, consistent with labeling of tubular elements. In contrast, in situ hybridization with the AT1 subtype selective probes revealed that AT1A receptor mRNA was primarily localized to the vasa recta and diffusely to the outer stripe of the outer medulla and the renal cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864160 TI - Short-term response of nonurea organic osmolytes in human kidney to a water load and water deprivation. AB - The cells of the inner medulla of the mammalian kidney accumulate high concentrations of nonurea organic osmolytes. The organic osmolytes found in the kidney include glycine betaine and sorbitol. This study was designed to measure changes in the urinary excretion of glycine betaine and sorbitol and the plasma concentration of glycine betaine in response to an acute water load (20 ml/kg) or acute water deprivation in young healthy males. In response to a water load the urinary excretion of glycine betaine and sorbitol increased parallel with or shortly after urinary urea excretion. The increase in urinary urea and sorbitol excretions preceded maximum minute volume, whereas peak glycine betaine excretion was closely related to maximum urine minute volume. Subsequently, urea, sorbitol, and glycine betaine excretion rates returned to baseline. In contrast, during water deprivation no change in glycine betaine, sorbitol, and urea urinary excretions occurred during the study period. Plasma glycine betaine concentration was stable during both diuresis and antidiuresis. We conclude that the organic osmolytes glycine betaine and sorbitol are components of a physiological and dynamic system in response to an acute water diuresis. PMID- 7864161 TI - Bicarbonate transport along the loop of Henle effects of adrenal steroids. AB - The role of adrenal steroids in the regulation of bicarbonate absorption in the loop of Henle was studied by in vivo microperfusion. Bicarbonate transport (JHCO3) was measured by microcalorimetry and fluid reabsorption by [14C]inulin, 7 10 days after surgery, in 1) sham-operated control rats, 2) adrenalectomized (Adx) rats, 3) Adx rats receiving dexamethasone (1.2 micrograms.100 g body wt 1.24 h-1) and a low dose of aldosterone (0.5 micrograms.100 g body wt-1.24 h-1), 4) Adx rats receiving dexamethasone, 5) Adx rats receiving a low dose of aldosterone, and 6) Adx rats receiving a high dose of aldosterone (1.0 micrograms.100 g body wt-1.24 h-1). JHCO3 along the loop of Henle was decreased by 40% in Adx rats. JHCO3 was increased by dexamethasone alone and by dexamethasone plus a low dose of aldosterone to rates observed in fully supplemented Adx rats. Aldosterone given alone at a low physiological dose had no effect, but, when administered at a high dose, returned JHCO3 to normal. PMID- 7864162 TI - Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney. AB - Vascular endothelial growth factor (VEGF) may modulate vascular permeability, chemotaxis for monocytes, and protease activity. In addition, VEGF may play a role in embryonic and tumor angiogenesis. In fetal mouse kidney, VEGF mRNA and protein expression have been demonstrated. This finding led to the hypothesis that VEGF might be involved in renal growth and development. To further elucidate the role of VEGF in human kidney, expression of VEGF and its receptors, the specific tyrosine kinase receptors, fit-1 and KDR, were studied. In fetal (6-24 gestational wk; mesonephros and metanephros) and adult kidney, VEGF mRNA and protein could be colocalized in glomerular epithelia and collecting duct cells by in situ hybridization and immunohistology. By reverse transcription-polymerase chain reaction, mRNA of three VEGF isoforms, VEGF121, VEGF165, and VEGF189, were found in fetal kidney and cortex, isolated glomeruli, and medulla of adult human kidney. KDR and flt-1 mRNA were coexpressed in endothelia of glomeruli and in peritubular capillaries in fetal and adult kidney. These data support the assumption that VEGF and its receptors may influence renal ontogenesis. We speculate that the constitutive expression of VEGF in adult kidney may be required for the function of VEGF receptor positive-fenestrated endothelia in glomeruli and postglomerular vessels. The expression of VEGF in collecting duct and of its receptors in medullary capillaries may in addition be relevant for maintaining medullary osmolality. PMID- 7864163 TI - Branching points of renal resistance arteries are enriched in L-type calcium channels and initiate vasoconstriction. AB - The morphologic structures responsible for the drop in blood pressure along the preglomerular vasculature are not completely defined. Theoretical and videomicroscopic analyses of nonrenal vascular beds implicate bifurcations of resistance arteries as important sites of hemodynamic regulation. These structures contain pacemaker cells sensitive to calcium channel blockers and appear to initiate vasomotion. In the present study, we examined the possibility of functional diversity of smooth muscle cells along resistance arteries with regard to the density of voltage-gated L-type calcium channels. Staining of microdissected renal resistance arteries with Bodipy-labeled dihydropyridine and analysis by confocal microscopy showed enhanced binding at branching points compared with the distal sites in daughter vessels. Antibodies directed against the alpha 1-subunit of the dihydropyridine-sensitive calcium channels confirmed the enhanced expression of L-type channels predominantly at the sites of bifurcations of renal resistance arteries. Fluorescence digital-image analysis of freshly microdissected branches of cortical radial (interlobular) and arcuate arteries intravitally labeled with a calcium indicator, fluo 3, identified branching points as initiator sites of depolarization-induced intracellular Ca2+ concentration ([Ca2+]i) transients, which propagated along the vascular wall at the rate of 2.0 +/- 0.7 micron/s. Videomicroscopy of blood-perfused rat juxtamedullary resistance arteries showed that branching points exhibit more pronounced contractile responses to KCl-induced depolarization than distal sites along the daughter vessels. Collectively, these results demonstrate that branching points are enriched in L-type calcium channels, a finding that suggests these structures may serve as important regulators of renal hemodynamics. PMID- 7864164 TI - Acute inflammation is the harbinger of glomerulosclerosis in anti-glomerular basement membrane nephritis. AB - The degree of glomerular inflammation and injury during immune-mediated glomerulonephritis is felt to be critical to the eventual development of glomerulosclerosis, although the relative contributions of acute and chronic inflammation are uncertain. By grading the initial dose of antibody in accelerated anti-glomerular basement membrane nephritis, we observed that only animals with the most substantial acute inflammation (in terms of neutrophil influx and acute proteinuria) developed sustained proteinuria followed by an increase in serum creatinine and evidence of severe glomerulosclerosis. Chronic inflammation (i.e., glomerular macrophage influx and evidence of glomerular cell proliferation), in contrast, was evident without the development of glomerulosclerosis. Decreasing the degree of acute inflammation during severe nephritis by complement depletion diminished both the initial and sustained proteinuria and the influx of neutrophils, prevented the terminal increase in serum creatinine, and attenuated the evolution of glomerulosclerosis. Complement depletion, however, did not affect peak proteinuria, macrophage influx, or glomerular cell proliferation. Regression analysis of the entire data set demonstrated that acute (day 1) proteinuria was predictive of the eventual histopathological index, more so than chronic (day 7) proteinuria. To recapitulate, glomerulosclerosis following antiglomerular basement membrane nephritis appears to be substantially dependent on the degree of acute inflammatory injury. PMID- 7864165 TI - In vitro production of angiotensin II by isolated glomeruli. AB - The glomerulus has several components of the renin-angiotensin system (RAS). The purpose of this study was to evaluate the ability of glomeruli isolated from adult Wistar-Kyoto rats to produce angiotensin II (ANG II). When isolated glomeruli were incubated in Krebs buffer, the peak concentration of immunoreactive angiotensin (ANG) in the incubation medium, representing simultaneous production and degradation, occurred after 15 min of incubation (3.98 +/- 0.34 pg.mg protein-1.15 min-1, of which 18% was ANG II. When 125I labeled ANG II was incubated with isolated glomeruli, the half-life of ANG II was 6.06 min. Hence, we estimated ANG II production at 3.77 +/- 0.21 pg.mg protein 1.15 min-1. When angiotensinogen-rich serum was added to the incubation medium, ANG concentration at 15 min increased by 500-fold (1,978 +/- 44 pg.mg protein 1.15 min-1, P < 0.001). ANG concentration in the glomerular incubate responded to perturbations known to alter systemic RAS. Enalaprilat, chymostatin, propranolol, and renin antiserum decreased ANG concentration in glomerular incubate, whereas salt depletion increased this (P < 0.05). We conclude that the rat glomerulus can generate ANG II independent of neural, hormonal, or vascular control. PMID- 7864166 TI - IL-1 beta increases laminin B2 chain mRNA levels and activates NF-kappa B in rat glomerular epithelial cells. AB - The amount and distribution of laminin in the glomerular basement membrane (GBM) change in the course of many types of glomerular disease. Because interleukin-1 (IL-1) is thought to play a role in the pathogenesis of glomerulonephritis, it raises the possibility that this and other cytokines might regulate laminin gene expression. To determine whether laminin B2 chain mRNA levels change in response to cytokines, total mRNA from rat glomerular epithelial cells (GEC) grown in culture was analyzed by Northern blots. These studies showed an increase in laminin B2 chain mRNA levels in GEC treated with IL-1 beta. Nuclear factor kappa B (NF-kappa B) is a cytokine-responsive factor that regulates transcription of many genes from the cognate kappa B enhancer element. The mouse laminin B2 chain promoter contains several kappa B-like motifs, suggesting that NF-kappa B might be involved in IL-1-induced laminin B2 chain gene expression. Nuclear extracts from IL-1 beta-treated GEC showed increased binding to the immunoglobulin kappa B enhancer element and to a kappa B consensus sequence from the murine laminin B2 chain promoter in an electrophoretic mobility-shift assay (EMSA). The immunoglobulin kappa B and the laminin B2 chain kappa B-like motifs competed for the same DNA binding activity in nuclear extracts from IL-1 beta-treated GEC. Pretreatment of these nuclear extracts with antibodies to either the p50 or p65 subunits of NF-kappa B abrogated the DNA binding activity recognized by either of the two DNA motifs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864167 TI - Dopamine and protein phosphatase activity in renal proximal tubules. AB - In the brain, dopamine, via protein kinase A (PKA) activation of dopamine- and cAMP-regulated phosphoprotein (DARPP-32), inhibits protein phosphatase 1 (PP1) activity and keeps Na(+)-K(+)-adenosinetriphosphatase (ATPase) in its phosphorylated inactive state. In the present study, we examined the relationship among dopamine, PP1, and Na(+)-K(+)-ATPase activities in renal proximal tubules. PP1 activity in proximal tubules was not decreased by dopamine (5 x 10(-9)-10(-4) M), fenoldopam (5 x 10(-6) M), or norepinephrine (5 x 10(-7) M). In contrast, in the medullary thick ascending limb of Henle and in the brain striatum, PP1 activity was decreased by fenoldopam (5 x 10(-6) M). We also showed that the ability of dopamine (10(-6) M) to inhibit Na(+)-K(+)-ATPase activity in proximal tubules (assessed by ouabain-sensitive 86Rb uptake) occurred in the absence or presence of a sodium clamp with 5 microM monensin. Thus the inhibitory effect of dopamine on Na(+)-K(+)-ATPase activity in proximal tubules is not regulated by PP1 activity. Tautomycin and okadaic acid by themselves, at concentrations that inhibited PP1 activity, had no effect on Na(+)-K(+)-ATPase activity in proximal tubules. The ability of a dopamine D1 agonist, fenoldopam, to inhibit PP1 activity in brain striatum and in medullary thick ascending limb, but not in proximal tubules, suggests differential organ and nephron segment regulation of PP activity. PMID- 7864168 TI - Biotinylation and assessment of membrane polarity: caveats and methodological concerns. AB - Studies of epithelial membrane polarity have been greatly facilitated through the use of the N-hydroxysuccinimide-biotin surface labeling technique (M. Sargiacomo, M. Lisanti, L. Graeve, A. Le Bivic, and E. Rodriguez-Boulan. J. Membr. Biol. 107: 277-286, 1989). We have used this technique in studies on the sorting and targeting of ion-transporting adenosinetriphosphatase molecules in polarized epithelial cells. Through efforts to optimize this technique in our experimental system, we have encountered several experimental conditions and circumstances where biotinylation is extremely inefficient and the assessment of membrane polarity which it provides is misleading. We demonstrate that the pH and ionic strength of the biotinylation buffer can dramatically affect biotin incorporation and that protocol-dependent variations in the recovery of biotinylated proteins can result in misrepresentation of the actual apical/basolateral distribution of a protein. Conditions and protocols that may improve the sensitivity and accuracy of this technique are discussed. PMID- 7864169 TI - Intravertebral ANG II effects on plasma renin and Na excretion in dogs at constant renal artery pressure. AB - Studies were performed to determine whether intravertebral angiotensin II infusion (iva ANG II) decreases renin release by increasing renal perfusion pressure (RPP) and to investigate possible effects of iva ANG II on renal function. RPP was electronically servocontrolled in 12 conscious dogs equipped with chronic vascular catheters and a suprarenal aortic balloon constrictor while iva ANG II was infused bilaterally for 60 min at 0.33 ng.kg-1.min-1. Without servocontrol, iva ANG II increased mean arterial pressure (MAP) from 101 +/- 4 to 106 +/- 5 mmHg, urine flow (V) from 0.36 +/- 0.03 to 0.45 +/- 0.04 ml/min, and sodium excretion (UNaV) from 36.2 +/- 7.0 to 62.7 +/- 6.6 mumol/min. Plasma renin activity (PRA) decreased from 6.9 +/- 0.7 to 5.0 +/- 0.6 ng ANG I.ml-1.3 h-1. With servocontrol, iva ANG II increased MAP from 102 +/- 4 to 109 +/- 5 mmHg while RPP remained constant with a variation of less than +/- 1 mmHg. PRA did not change significantly (5.9 +/- 0.3 to 7.0 +/- 0.7 ng ANG I.ml-1.3 h-1). V decreased from 0.33 +/- 0.02 to 0.26 +/- 0.01 ml/min, and UNaV decreased from 49.0 +/- 5.7 to 29.7 +/- 4.4 mumol/min. The data provide evidence that iva ANG II decreases renin release by increasing RPP and stimulating the renal baroreceptor and/or the macula densa mechanisms. In addition, at constant RPP, ANG II exerts a central action to decrease UNaV. PMID- 7864170 TI - Dietary protein does not alter intrinsic reactivity of renal microcirculation to angiotensin II in rodents. AB - The effect of dietary protein on renal function and on renal microvascular reactivity to angiotensin II was determined in rats fed a high-protein diet (40% protein), a low-protein diet (6% protein), or a normal diet (23% protein). Inulin clearance was higher in high-protein-fed rats (n = 7) than in rats fed a low protein diet (n = 7), 0.88 +/- 0.14 (means +/- SE) vs. 0.54 +/- 0.07 ml.min-1.g kidney wt-1 (P < 0.05). We also used videomicroscopy to assess the effect of angiotensin II on the renal microcirculation in a hydronephrotic kidney preparation. The afferent and efferent arterioles constricted to angiotensin II and norepinephrine in both high- and low-protein-fed rats; this constriction was diminished to angiotensin II but not to norepinephrine, in rats fed a high protein diet (-24.3 +/- 4.5, -20.2 +/- 4.2%) compared with rats fed a low-protein diet (-39 +/- 5.1, -39.1 +/- 5.7%). The vasoconstrictor responses to angiotensin II in rats fed a high-protein diet and a normal diet were significantly greater following inhibition of angiotensin II formation with captopril but not in low protein-fed rats. The apparent high-endogenous level of angiotensin II among rats fed a high-protein diet may account for the diminished reactivity to exogenous angiotensin II. Thus alterations in intrinsic vascular reactivity to angiotensin II are not responsible for the altered hemodynamics associated with dietary protein. PMID- 7864171 TI - Epidermal growth factor inhibits Na-Pi cotransport and mRNA in OK cells. AB - The present study examined the effect of epidermal growth factor (EGF) on Na-Pi cotransport in a tubular epithelial cell line derived from the opossum kidney (OKP cells). EGF caused a time- and dose-dependent decrease in Na-Pi cotransport. The inhibition of Na-Pi cotransport by 10(-8) M EGF was first demonstrable after 18 h with maximal effect seen at 24 h. EGF inhibited Na-Pi cotransport by decreasing the maximal velocity (10.8 +/- 0.9 in control vs. 4.9 +/- 0.8 nmol 32Pi.4 min-1.mg protein-1 in EGF, P < 0.001). Northern blot analysis indicated that EGF caused a significant decrease in NaPi-4 mRNA abundance. The abundance of NaPi-4 mRNA relative to beta-actin and/or glyceraldehyde-3-phosphate dehydrogenase mRNA was decreased by twofold in OK cells treated with EGF for 4 h and threefold in OKP cells treated with EGF for 24 h. Thus the decrease in NaPi-4 mRNA abundance preceded the decrease in Na-Pi cotransport activity. Inhibition of transcription with actinomycin D and protein synthesis with cycloheximide prevented the inhibition of Na-Pi cotransport. Furthermore, inhibition of phospholipase C activity with U-73,122 also significantly blocked the inhibitory effect of EGF on Na-Pi cotransport. The results indicate that EGF-induced decrease in OKP Na-Pi cotransport is mediated through a decrease in NaPi-4 mRNA and activation of the phospholipase C signaling pathway. PMID- 7864172 TI - cAMP modulates transepithelial resistance response of LLC-PK1 renal epithelia to tumor necrosis factor. AB - For "leaky" epithelia the transepithelial resistance (Rt) is an electrophysiological measure of the paracellular pathway within the epithelial barrier. The Rt across a monolayer of LLC-PK1 porcine renal epithelial cells is specifically an inverse measure of paracellular transepithelial permeability and displays a multiphasic and reversible response to the cytokine tumor necrosis factor-alpha (TNF). The Rt response to TNF can be inhibited by the nonhydrolyzable adenosine 3',5'-cyclic monophosphate (cAMP) analogue, dibutyryl cAMP. In addition, activation of adenylate cyclase (forskolin) or inhibition of phosphodiesterase (3-isobutyl-1-methylxanthine, Ro-20-1724, and pentoxifylline), each of which have been reported to elevate cellular cAMP levels, also inhibited the Rt response to TNF. Incubation of the LLC-PK1 cell sheet with N-[2 (methylamino)ethyl]-5-isoquinolinesulfonamide, an inhibitor of cAMP-dependent protein kinase (PKA), potentiated the Rt response to TNF. The Rt response to TNF was completely prevented by preincubation of the cultures with cholera toxin, whereas pertussis toxin pretreatment had a slight but significant potentiating effect on the response. Pretreatment with cholera toxin was associated with an approximately 18-fold elevation in cAMP levels in both control and TNF-treated cultures. Measurements of cellular cAMP content at selected intervals after TNF administration showed a significant elevation (P < 0.01) of 140% above time matched controls at 1 h after the administration of TNF to the cell sheet. The level of cAMP then declined to approximate control level within 2.5 h of TNF administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864173 TI - A novel cGMP-activated Cl- channel in renal proximal tubules. AB - Cl- channels activated by natriuretic peptides were detected in cultured rat proximal convoluted tubule (PCT) cells with the use of patch-clamp methodology. Bath application of atrial natriuretic peptide (ANP) activates a 150-pS Cl- channel with the open probability (Po) of the channel increasing from 0.0008 +/- 0.0003 to 0.021 +/- 0.008. 8-Bromoguanosine 3',5'-cyclic monophosphate (8 BrcGMP), a membrane-permeable analogue of cGMP, increased channel activity in the on-cell mode. In inside-out patches the channel was activated by cGMP in a dose dependent manner. Channel activity decreased after washing out and increased on reapplication of cGMP. A similar activation was observed also in presence of either of two protein kinase inhibitors, N-[2-(methylamino)ethyl]-5 isoquinolinesulfonamide dihydrochloride or KT5823, or a phosphatase inhibitor. Bath application of urodilatin mimicked the action of ANP. Po of the channel was found to be independent of both voltage and Ca2+, and gating activity could be blocked by the stilbene, 4,4-dinitrostilbene-2,2-disulfonic acid. These results demonstrate a Cl- conductance in PCT cells modulated by ANP and urodilatin via their second messenger, cGMP. PMID- 7864174 TI - Pathways involved in PTH-induced rise in cytosolic Ca2+ concentration of rat renal proximal tubule. AB - Parathyroid hormone (PTH) raises cytosolic Ca2+ concentration ([Ca2+]i) in isolated or cultured renal proximal tubule cells. The pathways through which this action is mediated are not fully delineated. This study explored these pathways utilizing fura 2. [Ca2+]i of freshly prepared renal proximal tubular cells increased from 150 +/- 3.6 to 281 +/- 9.0 nM after the exposure to 10(-7) M angiotensin II, which served as a positive control. Both PTH-(1-84) and PTH-(1 34) produced a dose-dependent rise in [Ca2+]i. The effects of both moieties were similar up to 10(-7) M, but with higher doses the rise in [Ca2+]i with PTH-(1-84) was greater (P < 0.01) than with PTH-(1-34). This effect of the hormone occurred in the presence or absence of calcium in the media, but the rise in [Ca2+]i was significantly greater in the presence of calcium. The PTH-induced rise in [Ca2+]i was markedly inhibited by PTH antagonist [Nle8,18,Tyr34]bPTH-(7-34)-NH2 (bPTH is bovine PTH), verapamil, or nifedipine. 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, increased [Ca2+]i of cells, but its effect was less than PTH. Staurosporine abolished the TPA effect and partially inhibited that of PTH. A G protein activator raised [Ca2+]i, whereas a G protein inhibitor and pertussis toxin partially blocked the effect of PTH. Sodium or chloride channel blockers or sodium-free media did not modify the effect of PTH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864175 TI - Interaction between cGMP-dependent dilators and autoregulation in rat preglomerular vasculature. AB - The influence of guanosine 3',5'-cyclic monophosphate (cGMP)-dependent dilators on autoregulatory responses (AR) of arcuate arteries (ArcA) and afferent arterioles at early sites and at juxtaglomerular sites (JAA) was assessed by videomicroscopy using in vitro blood-perfused juxtamedullary nephron preparations. AR were quantified as fractional changes in luminal diameter induced by doubling blood perfusion pressure (60-120 mmHg). Baseline AR ranged from 17 +/- 2% to 21 +/- 2% in ArcA and from 24 +/- 2% to 34 +/- 4% in JAA. Direct perivascular applications of increasing concentrations of 8-bromo-cGMP (8 BrcGMP, 10 microM to 1 mM), of the NO donors sodium nitroprusside (10 microM to 1 mM) and 3-morpholino-sydnonimine chlorhydrate (SIN1; 10 microM to 1 mM), and of rat atrial natriuretic factor (ANF, 0.1 nM to 10 nM) dose- and pressure dependently dilated all vessels at 60 mmHg. Concomitantly, AR values were dose dependently reduced or reversed to pressure-induced dilations. During application of 8-BrcGMP and NO donors, the segmental gradient of sensitivity of AR was ArcA > JAA; the opposite gradient was found with ANF (i.e., JAA > ArcA). The present results demonstrate that compounds known to utilize the cGMP-signaling pathway act as modulators of AR along the juxtamedullary preglomerular vasculature. PMID- 7864176 TI - Electrogenic sodium absorption and chloride secretion by an inner medullary collecting duct cell line (mIMCD-K2). AB - The initial segment of the inner medullary collecting duct (IMCDi) absorbs Na+ by an electrogenic mechanism and plays an important role in regulating the composition and volume of the urine. The purpose of the present study was to establish a permanent cell line derived from the IMCDi, which has the ion transport properties of the IMCDi in vivo. To this end, we isolated IMCD cells from the IMCDi of a mouse, Tg(SV40E) Bri 7, transgenic for the early region of SV40 (large T antigen) and established a permanent cell line, mIMCD-K2, by clonal dilution. mIMCD-K2 cells retain many differentiated characteristics of the IMCDi, including amiloride-sensitive electrogenic Na+ absorption stimulated by nanomolar concentrations of aldosterone. Aldosterone (1.5 x 10(-6) M) increased Na+ absorption from 0.2 +/- 0.1 to 4.6 +/- 1.7 microA/cm2. In addition, the cells secrete Cl- by an electrogenic mechanism at a rate of 0.5 +/- 0.1 microA/cm2. We propose that IMCDi cells either absorb or secrete NaCl depending on NaCl homeostasis. The mIMCD-K2 cell line should be useful for studying the cellular mechanisms responsible for electrogenic Na+ and Cl- transport in the IMCDi. PMID- 7864177 TI - Soluble TNF binding proteins modulate the negative inotropic properties of TNF alpha in vitro. AB - Soluble tumor necrosis factor (TNF) binding proteins (TNF-BPs) were characterized with respect to their capacity to modulate the negative inotropic properties of TNF-alpha in isolated contracting cardiac myocytes. Three TNF-BPs were evaluated: two natural monomeric human TNF monomeric binding proteins, TNF-BP1 and TNF-BP2, and sTNFR:Fc, a dimer of two molecules of human TNF-BP2 linked by the Fc portion of the human immunoglobulin G1 molecule. When TNF-alpha (25 pM) was allowed to form TNF-BP-TNF-alpha complexes, the negative inotropic effects of TNF-alpha were completely prevented by "neutralizing concentrations" of TNF-BPs, whereas lesser concentrations of TNF-BPs only partially attenuated the negative inotropic effects of TNF-alpha. The dimeric binding protein sTNFR:Fc was more effective on a molar basis than either of the monomeric binding proteins (TNF-BP1 or TNF-BP2) with respect to blocking the negative inotropic effects of TNF-alpha. When cardiac myocytes that had been treated with TNF-alpha (25 pM) were exposed to neutralizing concentrations of TNF-BP1, TNF-BP2, and sTNFR:Fc, the negative inotropic effects were completely reversed within 30 min. Thus these studies show for the first time that TNF-BPs are sufficient to prevent, as well as reverse, the negative inotropic properties of TNF-alpha in vitro. PMID- 7864178 TI - Dual regulation of L-type Ca2+ channels by serotonin 2 receptor stimulation in vascular smooth muscle cells. AB - The purpose of the present study was to investigate regulation of voltage dependent Ca2+ channels by serotonin in rat aortic smooth muscle cells in primary culture. L- and T-type Ca2+ currents (ICa) were recorded using the whole cell voltage-clamp method. Without pretreatment, in 25 of 30 cells examined, 10 microM serotonin decreased L-type ICa to various extents (-14 to -72%). However, in the remaining five cells, serotonin increased L-type ICa 21 +/- 4%. Thus, in 30 cells, serotonin decreased L-type ICa an average of 22 +/- 5%. In the presence of intracellular heparin (100 micrograms/ml), a blocker of inositol 1,4,5 trisphosphate binding to its receptor, serotonin increased L-type ICa in all cells 29 +/- 3% (n = 6). When stored Ca2+ was depleted by pretreatment either with 20 microM ryanodine and 20 mM caffeine or with 100 nM A-23187, serotonin also increased L-type ICa in all cells 30 +/- 5 (n = 4) or 37 +/- 5% (n = 12), respectively. In the presence of heparin, the serotonin-induced increase of L type ICa was prevented by 100 nM staurosporine (2 +/- 3%; n = 6, P < 0.01). The serotonin-induced decrease of L-type ICa was significantly augmented by 100 nM staurosporine (-43 +/- 10%; n = 5). Phorbol 12,13-dibutylate (PDBu; 1 microM) increased L-type ICa 29 +/- 3% (n = 6), and serotonin did not further increase L type ICa after its potentiation by PDBu.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864179 TI - Origin of regional pressure gradients in the left ventricle during early diastole. AB - Left ventricular (LV) pressure (P)-diameter, LVP-area, or LVP-volume relationships used to evaluate LV diastolic function assume uniform LV wall motion and constant LVP. Contrary to these assumptions, there are significant differences in ventricular dynamic geometry and in LV pressures measured simultaneously in different parts of the LV, particularly during early diastole. We instrumented six anesthetized open-chest dogs with three pairs of orthogonal ultrasonic crystals (anterior-posterior and septal-free wall minor axes, and base apex major axis) and two micromanometers (in the apex and in the LV base). The mitral valve occluder was implanted during standard cardiopulmonary bypass in the mitral annulus. Data were recorded during 11 transient vena caval occlusions. The mitral valve was occluded for 1 beat every 6-8 beats during each vena caval occlusion to produce nonfilling diastole. With the decrease of the LV end systolic volume (Ves) below the equilibrium volume Veq (volume of the completely relaxed LV at LVP = 0); the minimum negative LVP in nonfilling beats increases, the shape of the ventricle is more ellipsoidal in both filling and nonfilling beats, and the base-to-apex pressure gradient at the time of LVP minimum increases regardless of the presence or absence of filling. Thus heterogeneous myocardial stresses during isovolumic relaxation and early diastole result in ventricular shape changes, intraventricular redistribution of chamber volume, local accelerations of blood, and associated intraventricular LVP gradients. The role of elastic recoil assumes greater importance at Ves smaller than Veq, when the left ventricle becomes more ellipsoidal in shape during isovolumic relaxation, leading, in turn, to greater shape changes and greater LVP gradient. PMID- 7864180 TI - Pressure wave propagation and input impedance in thoracic aorta of conscious newborn sheep. AB - Aortic hemodynamics were examined in eight conscious newborn sheep. Flow and pressure in the thoracic aorta and pressure in the distal abdominal aorta were measured under control conditions and during pressure changes caused by bottle feeding or during intravenous infusions of nitroprusside, norepinephrine, or angiotensin II. Vasoconstriction affected aortic impedance, pressure wave amplification, and wave velocity similarly whether induced by feeding or by drugs. Central hemodynamics in the lamb were surprisingly similar to hemodynamics in the sheep fetus despite major changes in cardiovascular function at birth, largely because pressure-related increases in pulse wave velocity postpartum compensated for increased arterial lengths and increased heart rate. Wave reflection effects on pressure-flow relations were more prominent during vasoconstriction and less prominent during nitroprusside. Wave reflections in both lambs and fetal sheep return to the heart in early diastole; therefore, they do not add to ventricular afterload. Early diastolic return of reflected waves characterizes adults of many species, and demonstration of the phenomenon throughout the perinatal period reinforces arguments for its adaptive value. PMID- 7864181 TI - Cortical cerebral blood flow cycling: anesthesia and arterial blood pressure. AB - Cycling of various cerebral metabolic substances, arterial vascular diameter, and flow has been noted by many workers at a frequency near 0.1 Hz. Suspicion that this phenomenon is dependent on the type of anesthesia led us to investigate the occurrence of cerebral blood flow (CBF) cycling with different anesthetics. Fifteen Sprague-Dawley rats were anesthetized with either pentobarbital (n = 5, 40-50 mg/kg), alpha-chloralose (n = 5, 60 mg/kg), or halothane (n = 5, 1-0.5%). Body temperature was maintained at 37 degrees C. Femoral arterial and venous catheters were placed, and a tracheotomy was performed, permitting artificial ventilation with 30% O2-70% N2. A closed cranial window was formed over a 3-mm diameter craniotomy. Mean arterial pressure (MABP), arterial partial pressures of CO2 and O2 (PaCO2 and PaO2), and pH were controlled and stabilized at normal values. CBF was determined using laser Doppler flowmetry. To induce cycling, MABP was transiently and repeatedly lowered by exsanguination. Fast Fourier analysis of selected 64-s flow recordings (n = 38) was performed. CBF cycling was observed, independent of the type of anesthesia, in all animals. In 36 epochs, cycling was induced when MABP was reduced to a mean pressure of 65 +/- 1.5 mmHg. The mean frequency and amplitude were 0.094 +/- 0.003 Hz and 6.6 +/- 0.5%, respectively. Cycling occurred without blood withdrawal in two epochs. With the use of the blood-withdrawal epochs (n = 36), all three anesthetics shared a common linear slope between amplitude and blood pressure (P < 0.02) and blood pressure change (P < 0.01). Pentobarbital differed from alpha-chloralose and halothane in the relation between cycling frequency and blood pressure. Only pentobarbital exhibited correlation between frequency and blood pressure (P < 0.02) and blood pressure change (P < 0.001). The occurrence of these oscillations is not related to the type of anesthesia, and they usually occur at MABP values that are near or just above the lower limit of autoregulation. At this pressure level, CBF oscillations would suggest that vasoconstrictive and dilatory forces are no longer in balance, but alternatively vying for control. PMID- 7864182 TI - Thyroid status and potassium currents in rat ventricular myocytes. AB - The size and rate dependence of the transient (Ito) and steady-state (Iss) outward potassium currents were investigated in isolated rat ventricular myocytes obtained from euthyroid, hyperthyroid, and hypothyroid rats, using the whole cell, suction electrode voltage-clamp method. Under hypothyroid conditions Ito was reduced in size, with no significant change in Iss. In hypothyroid cells, the rate dependence of both currents was greatly enhanced, resulting in a much larger attenuation with increasing stimulation rates. A significant slowing of the recovery kinetics of Ito was observed. These effects of hypothyroidism were reversed by physiological triiodothyronine (T3) replacement. These current changes were reflected in an altered rate dependence of the action potential configuration in hypothyroid myocytes. Under hyperthyroid conditions no significant changes were observed in the amplitude or time course of recovery of Ito. Iss amplitude was increased, but no changes were found in its rate dependence. These results are discussed in terms of hormonal, long-term modulation of potassium currents, and in terms of cardiac pathology under conditions of altered thyroid status. PMID- 7864183 TI - Evidence for CGRP accumulation and activity in experimental neuromas. AB - Calcitonin gene-related peptide (CGRP) is a potent vasodilator and widely distributed neuropeptide that may participate in the injury response of peripheral nerve. We examined evidence for the presence of CGRP immunoreactivity (IR) and its activity in experimental neuromas of Sprague-Dawley rats created by sectioning the midsciatic nerve with resection of 2-3 cm of its distal portion and branches. CGRP activity was evaluated by measuring local blood flow in neuromas using hydrogen polarography and laser-Doppler flowmetry. At all time points studied after nerve section (24 h, 48 h, 7 days, 14 days) there was a rise in local blood flow in the neuroma stumps. At 48 h the hyperemia was maximum but was reversed by topical application of human CGRP(8--37), a specific CGRP receptor antagonist. CGRP presence was evaluated by immunohistochemistry and radioimmunoassay (RIA). At 24 and 48 h, CGRP IR was intense and distributed in a globular and diffuse pattern apparently not confined to discrete axonlike profiles. At 7 and 14 days, CGRP IR remained prominent and was associated with disorganized axonlike profiles, sometimes directed in a circumferential pattern around the outside of the neuroma. RIA confirmed rises in CGRP content at 24 and 48 h that accompanied the changes in local blood flow and altered distribution of CGRP IR. CGRP accumulates in a time-related fashion within experimental neuromas, where it induces among other possible actions prominent local vasodilatation. CGRP may be important in the regenerative milieu of injured nerves. PMID- 7864184 TI - Mechanisms of hypercapnia-stimulated PG production in piglet cerebral microvascular endothelial cells. AB - High CO2 stimulates dilator prostanoid (prostaglandin; PG) synthesis by piglet cerebral microvascular endothelial cells, but the mechanism of stimulation is unclear. We address the hypothesis that intracellular pH (pHi) and Ca2+ signaling are involved. When extracellular pH (pHe) and PCO2 were constant and pHi was rapidly reduced (propionate or nigericin), PG synthesis was stimulated. When pHe was lowered by reducing NaHCO3, pHi fell slowly, but PG synthesis was not altered. When pHe was decreased by increasing PCO2 or returned to 7.4 by increasing NaHCO3, with a constant PCO2 of 100 mmHg, pHi dropped quickly and PG synthesis was stimulated. When pHi was reduced slowly by changing CO2 slowly, or by stepwise addition of propionate, PG synthesis was increased regardless of pHe, suggesting that the rapid decline of pHi plays a central role in mediating the PG synthesis. Ca2+ signaling is a potential mechanism by which pHi increases PG synthesis. However, extracellular Ca2+ removal did not affect PG synthesis induced by propionate or hypercapnia. Furthermore, neither rapid nor slow decreases of pHi altered cytosolic free Ca2+ concentration. Therefore, Ca2+ signals do not appear to be involved in the CO2 stimulation of PG synthesis. PMID- 7864185 TI - Regional differences in IK density in canine left ventricle: role of IK,s in electrical heterogeneity. AB - Delayed rectifier K+ current (IK) was studied in isolated myocytes from canine left ventricular epicardium and midmyocardium using whole cell patch-clamp techniques. IK density during activation was greater in epicardial vs. midmyocardial myocytes [1.06 +/- 0.09 vs. 0.66 +/- 0.09 pA/pF (SE); P < 0.01] measured during 3-s depolarizing pulses to +25 mV. IK density was greater in epicardial myocytes at all times examined (range 150 ms to 3 s, +25 mV) and on termination of 3-s test pulses (potentials +5 to +65 mV). Greater IK density could not be explained by differences in activation kinetics or voltage dependence of activation. Two components of IK (IK,r and IK,s) have been described in guinea pig myocytes (Sanguinetti, M. C., and N. Jurkiewicz, J. Gen. Physiol. 96: 192-214, 1990). To assess whether differences in IK density could be ascribed to IK,r or IK,s, tail currents were fit to the sum of two decaying exponentials, with each component analogous to IK,s and IK,r based on sensitivity to E-4031 and rectification properties. Greater tail current density in epicardial myocytes was due to greater IK,s with no discernible difference in IK,r. These results suggest that regional differences in IK density in left ventricular epicardium are due to a larger IK,s component, which contributes to ventricular electrical heterogeneity and may reflect the differential expression of the IsK channel. PMID- 7864186 TI - Protective effect of hypoxia on mechanical and metabolic changes induced by hydrogen peroxide in rat hearts. AB - The effect of hypoxia (20% O2 for 5 min) on the hydrogen peroxide (H2O2)-induced myocardial change was studied in the Langendorff rat heart, which was perfused at a constant flow rate and driven electrically. H2O2 decreased the left ventricular developed pressure, increased the left ventricular end-diastolic pressure, and decreased the myocardial ATP level. These mechanical and metabolic alterations induced by H2O2 were less prominent in the hypoxia-reoxygenated heart than in the normoxic heart (i.e., hypoxia had a protective effect on the H2O2-induced change). Both 8-phenyltheophylline (8-PT), a nonselective adenosine-receptor antagonist, and glyburide (Gly), an inhibitor of the ATP-sensitive potassium (KATP) channel, significantly reduced the protective effect of hypoxia. The adenosine A1-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DP-CPX) reduced the protective effect of hypoxia incompletely. Gly, 8-PT, and DPCPX did not affect the mechanical function and energy metabolism of the hypoxia reoxygenated heart without H2O2. These results suggest that brief and mild hypoxia attenuates the H2O2-induced mechanical and metabolic changes and that the protective effect of hypoxia is probably mediated by activation of the adenosine receptors, which open the KATP channel. PMID- 7864187 TI - Nonlinear chaotic dynamics of arterial blood pressure and renal blood flow. AB - To determine whether arterial pressure (AP) and renal blood flow (RBF) are nonlinear dynamic processes (chaotic), we measured resting AP and RBF over 4 h in six conscious dogs. A catheter was placed in the aorta, and transit-time flowmeters were positioned around the renal artery. The average AP was 102 +/- 3 mmHg, and the mean RBF was 318 +/- 42 ml/min. We applied four analytic procedures to test the nature of AP and RBF time series, i.e., to determine if these variables are controlled randomly, if they consist of periodic oscillations, or whether they are best characterized as nonlinear dynamic processes. To this end, a fast Fourier transform was performed to quantify the amount of distinct periodic oscillations and nonperiodic variability in the very low frequency domain (< 0.01 Hz). The power spectrum of AP and RBF revealed broad band noise with no distinct peaks, which is commonly referred to as "1/f noise." As a second procedure, time-delayed phase return maps were constructed, and as a third approach the correlation dimensions were estimated via the Grassberger-Procaccia algorithm. The correlation dimensions of RBF and AP were similar (RBF 3.3 +/- 0.37 vs. AP 3.6 +/- 0.23; P = 0.2). The fourth method determined sensitive dependence on initial conditions, a hallmark of nonlinear "chaotic" dynamics. We determined the maximal Lyapunov exponents and found them to be positive for AP (0.1 +/- 0.01) and for RBF (0.04 +/- 0.01) indicating that they both are nonlinear dynamic processes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864188 TI - Increased thromboxane-mediated contractions of retinal vessels of newborn pigs to peroxides. AB - The vasomotor effects of three peroxides (H2O2, cumene hydroperoxide, and t-butyl hydroperoxide) on the retinal vasculature, as well as the role of thromboxane in these effects, were studied using time-frame photography of isolated eyecup preparations from newborn and adult pigs. All three peroxides caused constriction of retinal arteries and veins, and these effects were greater in the newborn than in the adult. The cyclooxygenase inhibitor indomethacin, the thromboxane synthase blocker CGS-13080, and the thromboxane receptor blockers GR-32191B and L-670,596 inhibited the peroxide-induced vasoconstriction. The peroxides also increased thromboxane levels in the retina, and this increase was greater in newborn than in adult tissues. Both indomethacin and CGS-13080 prevented the peroxide-induced increase in retinal thromboxane. The thromboxane analogue U-46619 also produced constriction of newborn and adult retinal vessels, but its effects on the retinal veins of newborn pigs were less than those on adult veins. Data indicate an important role for increased production of thromboxane in the relative increase in the vasoconstrictor effects of peroxides on the newborn retinal vasculature. These findings suggest that the vasoconstriction and occlusion after oxidative stresses, which precede retinal neovascularization, are mediated by thromboxane. PMID- 7864189 TI - An integrated model of LV muscle mechanics, coronary flow, and fluid and mass transport. AB - An integrated left ventricular (LV) model that accounts for the three-phase (fiber-blood-interstitium) myocardial structure and composition is used to study the interactions among myocardial mechanics, coronary flow, and fluid and mass transport. Effects of ventricular load, coronary perfusion pressure, and fluid and mass transport on ventricular performance and coronary dynamics are studied here. In agreement with experimental observations, the analysis shows that 1) coronary flow impediment is not significantly affected by changes in the afterload and preload at constant coronary perfusion pressures, 2) an increase in coronary perfusion pressure increases the intramyocardial pressure (IMP) as well as the mean flow and oscillatory flow amplitude, 3) contractility has a direct effect on IMP and coronary flow impediment, and 4) changes in blood osmolarity and lymphatic outflow, which may cause myocardial edema, affect both ventricular mechanics and coronary flow. Clearly, accounting for fluid and mass transport allows to study the interactions among coronary flow, ventricular and myocardial mechanics, and intramyocardial fluid shifts. PMID- 7864190 TI - Chronic central potassium infusion prevents deoxycorticosterone-salt hypertension in rats. AB - Although it has long been established that cerebrospinal fluid potassium concentration (CSF [K]) is very tightly regulated, it has been reported that rats made hypertensive by central infusions of aldosterone have significantly lower CSF [K] compared with normotensive controls. We investigated whether reduced CSF [K] is also present in another animal model of hypertension, the deoxycorticosterone acetate (DOCA)-salt rat, and we hypothesized that chronic intracerebroventricular (IVT) infusion of potassium with miniosmotic pumps might attenuate the rise in blood pressure observed in these rats. DOCA-salt rats without IVT infusions or with control CSF infusions (0.5 microliter/h of 2.9 mM K for 2 wk) had a significantly increased systolic blood pressure and a significantly lower CSF [K] compared with their respective sham groups. In contrast, DOCA-salt rats receiving IVT infusions with elevated [K] (10, 30, or 150 mM) had significantly lower blood pressures compared with those receiving control CSF. They also did not exhibit decreased CSF [K] compared with their respective sham groups. At 10 and 150 mM K, the blood pressure rise in DOCA-salt rats was not significantly different from shams. At 30 mM K, there was a slight, but significant, increase in blood pressure in the DOCA-salt rats compared with their shams, but this rise was still much less than in DOCA-salt rats infused with 2.9 mM K. Infusions with elevated [K] had no effect on blood pressure in the sham animals. These studies suggest that altered brain potassium homeostasis may play an important role in the development of DOCA-salt hypertension. PMID- 7864191 TI - Tone-dependent responses of histamine in feline pulmonary vascular bed. AB - Under conditions of controlled pulmonary blood flow and constant left atrial pressure, histamine produced tone-dependent responses in the pulmonary vascular (PV) bed of intact-chest, spontaneously breathing cats. At low, baseline PV tone, histamine produced dose-dependent increases in mean lobar arterial pressure that were antagonized by the selective histamine H1-receptor antagonist, diphenhydramine. The cyclooxygenase inhibitor, meclofenamate, and the thromboxane A2 (TxA2) receptor antagonist, SQ-29548, had no effect on these vasoconstrictor responses of histamine. After an increase in PV tone with an intralobar arterial infusion of a TxA2 mimic, U-46619, histamine produced vasodilator responses at low doses, biphasic vasodilator/vasoconstrictor responses at midrange doses, and vasoconstrictor responses at high doses. Diphenhydramine antagonized vasoconstrictor responses and the vasodilator responses of low to midrange doses and enhanced vasodilator responses of high doses of histamine at elevated PV tone. Selective H2-receptor antagonists, ranitidine and meclofenamate, and selective H3-receptor antagonist, thioperamide, did not antagonize vasodilator responses of histamine. H1- and H2-receptor antagonism was more effective in reducing the vasodilator responses of histamine at elevated PV tone than H1 receptor antagonism alone. These data support that histamine produces vasoconstrictor responses at low baseline and elevated PV tone by acting on H1 receptors that do not induce the release of vasoconstrictor prostanoids. At elevated PV tone, histamine produces vasodilation by acting on H1 receptors that are not coupled to the release of vasodilator prostaglandins and also, in part, by acting on H2 receptors. PMID- 7864192 TI - Daily spontaneous running attenuated the central gain of the arterial baroreflex. AB - Exercise training attenuates arterial baroreflex function. Mechanisms responsible may include an attenuated aortic baroreceptor reactivity (afferent mechanisms) and/or an attenuated central baroreflex gain. We tested the hypothesis that the aortic baroreceptor reactivity and/or central gain is attenuated by daily spontaneous running (DSR). Eighteen anesthetized Sprague-Dawley rats (11 control and 7 DSR) were tracheotomized and instrumented with femoral venous and right carotid arterial catheters. Electrodes were placed around the left aortic depressor nerve and the lumbar sympathetic trunk. Eight to thirteen weeks of DSR were associated with a 20% increase in heart weight-to-body weight ratio (2.83 +/ 0.04 vs. 3.39 +/- 0.10 g/kg; P < 0.001) and resting bradycardia (413 +/- 6 vs. 384 +/- 10 beats/min; P = 0.01). DSR reduced the central gain of the baroreflex regulation of heart rate (0.210 +/- 0.046 vs. 0.005 +/- 0.021 beats.min-1.%-1; P = 0.004) during decreases in arterial pressure. However, the reactivity of aortic baroreceptor afferents and the central gain of the baroreflex control of lumbar sympathetic nerve activity were not different in control and DSR rats. Thus DSR reduced the central gain of the arterial baroreflex regulation of heart rate without changing the reactivity of aortic baroreceptor afferents. We conclude that afferent mechanisms are not responsible for the training-induced reduction in arterial baroreflex function. PMID- 7864193 TI - Comparison of small artery sensitivity and morphology in pressurized and wire mounted preparations. AB - Two in vitro techniques, the pressurized flow chamber and the wire myograph, commonly employed to study the structure and function of small arteries, were compared. Mesenteric arteries from Wistar-Kyoto (WKY) rats were studied at a transmural pressure (44 +/- 1 mmHg) at which they elicit optimum contraction in each system. Differences in morphological parameters were minor, but there was a marked difference in the vasoconstrictor response of arteries mounted in the wire myograph and pressure system. Endothelium-intact pressurized arteries were significantly more sensitive to norepinephrine and constricted to angiotensin II, whereas wire-mounted vessels did not. These differences in agonist-induced contraction remained after removal of the endothelium. Blockade of amine uptake mechanisms indicated that the difference in norepinephrine sensitivity between the systems resulted from an enhanced influence of neuronal amine uptake in wire mounted arteries. These data demonstrate that the technique employed has important functional implications for the study of small artery responses in vitro and that the results of investigations into the pathophysiology of small arteries are dependent on the method used and must be interpreted with caution. PMID- 7864194 TI - Involvement of hydrogen and lipid peroxides in acute tobacco smoking-induced platelet hyperactivity. AB - Previous studies have established that cigarette smoking results in acute platelet hyperaggregability. We investigated whether changes in plasma oxidative properties could occur after smoking and whether such changes could be responsible for this enhanced platelet activity. In the present work, we report that platelets from nonsmokers become hyperactive after incubation with plasma prepared from blood of smokers obtained 10 min after smoking. This effect was not observed with presmoking plasma and could be inhibited in vitro by adding either catalase or reduced glutathione plus peroxidase to plasma or 2,6-di-tert-butyl-p cresol (BHT) to platelets before incubation. Comparison of pre- and postsmoking plasma showed that smoking resulted in a decrease in vitamin E (18%, P < 0.01) and increases in conjugated diene (35%, P < 0.001), thiobarbituric acid-reactive substance (23%, P < 0.02), and free fatty acid (FFA, 40%, P < 0.005) plasma concentrations. The FFA fraction was peroxidized to a higher extent when extracted from postsmoking than from presmoking plasma. This peroxidized FFA fraction enhanced the thrombin-induced aggregation of platelets from nonsmokers. This increased response was inhibited either when the peroxidized FFA fractions were isolated from plasma treated with reduced glutathione and peroxidase or by pretreatment of the platelets with BHT. We conclude that the enhanced formation of lipid hydroperoxides found in postsmoking plasma seems to be responsible for the acute and marked platelet hyperactivity observed after smoking. PMID- 7864195 TI - Relationship between cGMP and myocardial O2 consumption is altered in T4-induced cardiac hypertrophy. AB - We tested the hypothesis that increases in guanosine 3',5'-cyclic monophosphate (cGMP) would reduce myocardial O2 consumption and that thyroxine (T4)-induced (0.5 mg/kg for 16 days) cardiac hypertrophy would change this relationship. Anesthetized open-chest New Zealand White rabbits were divided into four groups: control vehicle (CV, n = 7), control nitroprusside (CN, n = 6), T4 vehicle (T4V, n = 8), and T4 nitroprusside (T4N, n = 8). Vehicle or sodium nitroprusside (10( 4) M) was topically applied to the left ventricular subepicardium for 15 min. Coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry) were used to determine O2 consumption. Guanylate cyclase activity and cGMP were determined by radioimmunoassay. T4 increased the heart weight-to-body weight ratio from 2.7 +/- 0.1 to 3.4 +/- 0.2. Topical application of nitroprusside had no significant hemodynamic effects. Nitroprusside significantly increased myocardial cGMP in control hearts (CV = 4.1 +/- 0.3 to CN = 12.4 +/- 5.0 pmol/g) and T4 hearts (T4V = 3.9 +/- 0.3 to T4N = 5.2 +/- 0.4). The increase in the level of myocardial cGMP was significantly greater in CN (+202%) than in T4N (+33%). There were no significant differences in basal or total guanylate cyclase activity between control and T4 rabbits. Myocardial O2 consumption significantly declined in both groups during nitroprusside (10.8 +/- 1.4 for CV to 7.3 +/- 1.0 for CN (-32%) and 13.6 +/- 1.2 for T4V to 9.9 +/- 1.4 ml O2.min-1.100 g-1 for T4N (-27%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864196 TI - Hemodynamic effects of dopamine, norepinephrine, and fluids in a dog model of sepsis. AB - To study how sepsis affects hemodynamic responses to catecholamines and fluids, either Escherichia coli-infected (septic, n = 8) or sterile (controls, n = 6) fibrin clots were implanted intraperitoneally into 2-yr-old beagles. Hemodynamics were measured at each of four doses of dopamine (0, 5, 10, and 20 micrograms.kg 1.min-1) and norepinephrine (0, 10, 20, and 40 micrograms.min-1), before and after infusion of fluid (Ringer 40 ml.kg-1). Septic animals had lower mean arterial pressure (MAP, P = 0.04), stroke volume index (SVI, P = 0.0001), and left ventricular (LV) ejection fraction (LVEF) (P = 0.0001) than controls. During this time, increasing doses of dopamine and norepinephrine produced corresponding increases (P < 0.001) in LVEF, SVI, and MAP. However, during sepsis, the ability of dopamine to increase MAP diminished, while its ability to increase LVEF and SVI was maintained. Conversely, the ability of norepinephrine to increase LVEF and SVI diminished, but its ability to increase MAP was maintained. During sepsis, fluids alone increased (P < 0.05) MAP, LVEF, SVI, and cardiac index (CI). Fluids with catecholamines also significantly increased (P < 0.05) MAP with only minimal increases in LVEF, SVI, and CI. These data demonstrate that during sepsis without catecholamines, fluids improve cardiac performance and systemic pressures, but with catecholamines, fluids have minimal effects on cardiac performance and augment MAP. Furthermore, during sepsis dopamine is more effective than norepinephrine in increasing LV performance, but norepinephrine is more effective than dopamine in increasing systemic pressures. PMID- 7864197 TI - CaMKII is responsible for activity-dependent acceleration of relaxation in rat ventricular myocytes. AB - We investigated the role of Ca/calmodulin-dependent protein kinase (CaMKII) in relaxation and cytosolic free [Ca] ([Ca]i) decline during steady-state (SS) and postrest (PR) twitches in intact rat ventricular myocytes. Half-time of mechanical relaxation and time constant of [Ca]i decline (tau) were twofold greater during PR than with SS at 1 Hz. This difference was 1) abolished by inhibition of sarcoplasmic reticulum (SR) Ca accumulation by thapsigargin or caffeine; 2) greater at higher stimulation frequency and extracellular [Ca], which affected only SS tau; 3) abolished by the protein phosphatase inhibitor okadaic acid (10 microM, which selectively accelerated [Ca]i decline during PR); 4) still present during stimulation or inhibition of adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) by 10 microM forskolin or 1 microM H 89, respectively (SS and PR tau values were abbreviated and prolonged, respectively); and 5) suppressed by 10 microM KN-62, a selective inhibitor of CaMKII, which selectively prolonged [Ca]i decline during SS twitches. Both protein kinase inhibitors were also shown to decrease the SR Ca-uptake rate in digitonin-permeabilized rat myocytes. We conclude that CaMKII plays a major role in modulation of relaxation in rat ventricular myocytes, enhancing SR Ca uptake in a activity-dependent fashion. Our results are also compatible with a background, activity-independent stimulation of SR Ca uptake by PKA in intact rat myocytes. PMID- 7864198 TI - Production of lactic acid and energy metabolism in vascular smooth muscle: effect of dichloroacetate. AB - Vascular smooth muscle metabolism is characterized by substantial production of lactic acid even under fully oxygenated conditions. The role the aerobic production of lactate plays in the energetics of smooth muscle is obscure and was investigated in this study. Helical strips of porcine carotid arteries were incubated in medium containing 1 mM dichloroacetate (DCA), an agent that stimulates pyruvate dehydrogenase and promotes the oxidation of glucose. Lactate production in resting muscle was decreased in the presence of DCA (0.033 +/- 0.006 vs. 0.111 +/- 0.014 mumol.g-1.min-1, P < 0.02), indicating diversion of glucose metabolism from lactate production to enhanced glucose oxidation. This was associated with reduction in the level of ATP+phosphocreatine (PCr) (0.99 +/- 0.01 vs. 1.40 +/- 0.09 mumol/g, P < 0.05) and cataplerosis of the tricarboxylic acid (TCA) cycle. Contraction by KCl was also associated with reduced lactate production in the presence of DCA (0.086 +/- 0.017 vs. 0.20 +/- 0.002 mumol.g 1.min-1, P < 0.01), but ATP+PCr normalized, and there was anaplerosis of the TCA cycle. Glycogen in control arteries declined by approximately 1.3 mumol/g over 30 min K+ contraction but was unchanged in the presence of DCA. By calculation, the glycogen spared could be accounted for by the quantity of glucose diverted from lactate production to glucose oxidation during contraction. It is concluded that the aerobic production of lactate is a mechanism affording optimal coordination and modulation of glucose supply and oxidative energy production with energy demand. PMID- 7864199 TI - Connexin 43 and connexin 40 gap junctional proteins are present in arteriolar smooth muscle and endothelium in vivo. AB - The distributions of connexin 43 (Cx43) and connexin 40 (Cx40) in smooth muscle and endothelium of resistance vessels were examined using indirect immunofluorescence techniques coupled with confocal microscopy. Cx43 and Cx40 were found in smooth muscle and endothelium. Similar staining patterns were found in microvessel samples from brain and cremaster of the rat and from arterioles of the hamster cheek pouch. Double-labeling studies showed a high degree of colocalization of Cx40 with Cx43, suggesting the presence of multiple connexins within a single junctional plaque. Quantitative comparisons were made of the fluorescent patterns in the endothelium and smooth muscle of rat brain arterioles. Cx43 and Cx40 plaque diameters were 0.9 +/- 0.1 and 0.8 +/- 0.1 (SE) microns, respectively, in the endothelial layer and 0.5 +/- 0.1 and 0.5 +/- 0.1 microns, respectively, in the smooth muscle. There was no difference between mean plaque diameters of Cx43 and Cx40 in endothelium or smooth muscle. However, plaques were significantly larger in endothelium than in smooth muscle (P < 0.05). These findings demonstrate the potential for cell-cell communication in both cell types of the wall of arterioles from three different tissues. The data also suggest a greater level of coupling within the endothelium. PMID- 7864200 TI - Mast cell degranulation and blood-nerve barrier permeability in rat sciatic nerve after 7 days of hyperglycemia. AB - The association between hyperglycemia and altered blood-nerve barrier permeability was examined after 7 days of experimental diabetes. In nerves of rats fed a diet of 40% galactose, permeability to [14C]mannitol [13.43 +/- 2.47 x 10(-5) (SD) ml.s-1.g dry wt-1] and water content [3.43 +/- 0.24 (SD) mg/mg dry wt] were significantly increased compared with control (9.24 +/- 2.09 x 10(-5) ml.s-1.g dry wt-1 and 2.15 +/- 0.28 mg/mg dry wt) and streptozotocin-diabetic animals (8.43 +/- 2.94 x 10(-5) ml.s.-1.g dry wt-1 and 2.35 +/- 0.56 mg/mg dry wt). Electron microscopy revealed significant increases in the number of degranulating perivascular mast cells and in an index of vasoconstriction in galactose-treated rats (3.8 +/- 1.6 and 0.160 +/- 0.062, respectively) compared with control (0.5 +/- 0.8 and 0.072 +/- 0.017, respectively) and diabetic animals (1.4 +/- 1.7 and 0.083 +/- 0.033, respectively). The data are consistent with a role for mast cells in permeability changes occurring after only 7 days of galactose intoxication. PMID- 7864201 TI - Immediate responses of endothelial cells to hypoxia and reoxygenation: an in vitro model of cellular dysfunction. AB - We have studied endothelial functions and integrity under clinically relevant levels of acute and profound hypoxia. Bovine aortic endothelial cells (EC) grown on microcarrier beads were exposed for 15-min intervals to normoxic (20% O2) or hypoxic (1-2% O2) medium. Control intervals were followed by four hypoxic and then four normoxic intervals for reoxygenation. Prostacyclin release from EC significantly decreased after only 15 min of hypoxia and remained low despite reoxygenation. This decrease in prostacyclin release was not coincident with decreased viable cells (Trypan blue exclusion) or with increased cell lysis (increased lactate dehydrogenase) after hypoxia or reoxygenation. When the medium was supplemented with 30 microM arachidonate (saturating concentration), prostacyclin release still significantly decreased after 30 min of hypoxia but returned to baseline levels by 30 min of reoxygenation. Similar results were obtained for thromboxane B2 release. These data suggest that 1) EC decrease prostacyclin release during acute, profound hypoxia, 2) EC decrease prostaglandin production during hypoxia despite abundant exogenous arachidonate, and 3) recovery of prostaglandin production is dependent on exogenous arachidonate during reoxygenation. PMID- 7864202 TI - Cholesterol distribution in rat heart myocytes. AB - Cholesterol oxidase was used to investigate the distribution of free cholesterol between plasma membrane and intracellular pools in cultured neonatal rat heart myocytes. Only 20% of the total unesterified cholesterol was converted to delta 4 cholestenone by cholesterol oxidase in intact cells. With increasing age in culture and concurrent hypertrophy, there was an increase in unesterified cellular cholesterol and plasma membrane cholesterol; their relative distribution remained unchanged. Electron micrographs of negatively stained samples of day 4 cytosol revealed the presence of vesicles 50-200 nm in diameter. Cholesterol monohydrate crystals were found in the cytosol of hypertrophic day 14 cells. Treatment of day 14 cells with small unilamellar vesicles of egg phosphatidylcholine reduced plasma membrane and intracellular cholesterol levels, resulting in the disappearance of the cholesterol monohydrate crystals and the formation of vesicles smaller than those observed in day 4 cultures. PMID- 7864203 TI - Humoral factor(s) in hypertensive rats trophic for cultured aortic smooth muscle cells. AB - Humoral factors in one-kidney, one-clip (1K,1C) hypertension in rats increase growth of smooth muscle cells cultured from rat arteries. To further characterize the plasma factor or factors involved, we prepared male rats with early, benign 1K,1C hypertension and paired them with one-kidney (1K) normotensive controls. In the presence of growth stimulated by background levels (1%) of fetal calf serum (FCS), plasma-derived serum (PDS), fresh or frozen, from 99 1K,1C rats differentially increased [3H]thymidine incorporation of growth-arrested rat aortic cells; increases were up to 93% more than those evoked by the paired 1K PDS and were concentration related (P < 0.01). However, there was no evidence for a differential effect of 1K,1C PDS in the absence of FCS nor of PDS after boiling. On the other hand, neither treatment of PDS with proteolytic enzymes nor charcoal absorption ablated this differential trophic effect. Thus this study provides evidence that the humoral factor(s) in hypertension are resistant to freezing, proteolysis, and charcoal absorption, but sensitive to boiling, and they require background levels of growth for expression. PMID- 7864204 TI - Phosphatidylethanolamine and sarcolemmal damage during ischemia or metabolic inhibition of heart myocytes. AB - Phosphatidylethanolamine (PE) is a nonbilayer-preferring and fusogenic phospholipid. It is kept in the bilayer configuration by interaction with other phospholipids in biologic membranes. However, reorganization of the membrane phospholipids could lead to expression of the nonbilayer nature of PE and induce bilayer instability. During ischemia a transbilayer reorganization of sarcolemmal PE is observed, and results have been published that suggest a lateral phase separation in the inner sarcolemmal leaflet phospholipids. These reorganizations and the subsequent expression of the nonbilayer behavior of PE are proposed to form the basis for sarcolemma destabilization and destruction. Lowering the PE content of myocytes, especially of the sarcolemma, is then expected to attenuate myocyte damage after simulated ischemia or metabolic inhibition. Culturing neonatal rat heart myocytes in the presence of N,N-dimethylethanolamine resulted in the synthesis of the bilayer-preferring N,N-dimethyl-PE and a lowering of the ratio between nonbilayer- and bilayer-preferring phospholipids from 0.58 to 0.30. This change in phospholipid composition did not impair cell functioning but did result in a strong attenuation of cell damage on ischemia or metabolic inhibition. A good correlation between the nonbilayer-preferring phospholipid content and the degree of cell damage was obtained (r = 0.98). These results provide further evidence that physicochemical properties of the sarcolemmal phospholipids play a crucial role in the sarcolemmal disruption during prolonged ischemia and/or reperfusion. PMID- 7864205 TI - Effects of hypertrophy on left atrial and ventricular compliance and plasma ANF levels in conscious dogs. AB - Alterations in left atrial (LA) and left ventricular (LV) compliance and arterial and coronary sinus atrial natriuretic factor (ANF) concentrations at baseline and in response to both volume depletion and expansion were investigated in 15 conscious dogs with aortic banding-induced LV hypertrophy (LVH) (LV/body wt increased by 64%), which also induced LAH (LA/body wt increased by 61%). With volume expansion coronary sinus ANF increased more (P < 0.05) in dogs with LVH (+427 +/- 88 pg/ml) compared with control dogs (+146 +/- 45 pg/ml). Arterial ANF levels also rose more with volume expansion in LVH. In dogs with LVH, the LV end diastolic pressure-diameter relationship was shifted to the left with a steeper slope with volume expansion, such that at any given diastolic dimension, diastolic pressure was higher. In contrast, the pressure-dimension relationship for the LA appendage was shifted in the opposite direction during both atrial systolic and diastolic phases, with a more shallow slope in hypertrophy compared with control dogs, resulting in an augmented pressure-dimension product during volume loading in LAH. In conclusion, in dogs with LVH and LAH, enhanced ANF was revealed in the coronary sinus and systemic circulation during volume expansion, which could be due, in part, to a more compliant, but hypertrophied, LA, which responded to equivalent volume loading with an augmented pressure-dimension product. PMID- 7864206 TI - Regulation of coronary diameter by myogenic mechanisms in arterial microvessels greater than 100 microns in diameter. AB - We performed the present study to determine the quantitative significance of transient and steady-state myogenic responses in isolated coronary resistance vessels greater than 100 microns in diameter. Small coronary arteries were isolated from freshly excised porcine hearts (n = 14) and were studied under static conditions in a superfused vessel chamber that allowed internal diameter to be assessed continuously using video microscopic techniques. At a mean distending pressure of 50 mmHg, the passive diameter of resistance arteries following sodium nitroprusside averaged 181 +/- 10 (SE) microns. Upon heating, vessels developed spontaneous tone and constricted to 72 +/- 3% of their maximum diameter. After a 30-mmHg step change in coronary pressure from 50 to 80 mmHg, there was an initial dilation from 131 +/- 9 to 149 +/- 11 microns, followed by myogenic constriction that returned diameter to the initial value over a period of several minutes (134 +/- 10 microns, P = NS). Directionally opposite peak transients were observed during reductions in pressure. Steady-state diameter remained relatively constant over a pressure range from 100 to 20 mmHg. Although these data demonstrate that myogenic responses are present in resistance arteries that are greater than 100 microns in diameter, their contribution to steady-state coronary resistance changes as pressure is varied is small. This suggests that additional mechanisms contribute to the phenomenon of coronary autoregulation in this class of resistance vessel. PMID- 7864207 TI - Influence of sympathetic tone on mechanical properties of muscular arteries in humans. AB - Although smooth muscle tone is a key determinant of mechanical properties of arteries in animal experiments, it has not yet been studied in humans because of technical limitations. To assess the influence of tone on arterial properties in humans and to emphasize the interest of calculation at specific stress, we used echo tracking and photoplethysmographic measurement of arterial pressure to study radial arterial mechanics during a cold pressor test (CPT) in 12 healthy volunteers (28 +/- 2 yr). During CPT, mean arterial pressure rose from 83 +/- 3 to 106 +/- 5 mmHg (P < 0.05), internal diameter decreased from 2.75 +/- 0.15 to 2.54 +/- 0.14 mm (P < 0.05), and wall thickness increased from 0.576 +/- 0.027 to 0.634 +/- 0.029 mm (P < 0.05). At a specific pressure (105 mmHg), midwall stress and incremental modulus decreased whereas arterial compliance increased. The incremental modulus of elasticity and compliance were fitted as functions of pressure and of midwall stress. CPT decreased the modulus about equally at all wall stresses measured. The modulus decreased and the compliance increased at every level of pressure measured. At all levels of midwall stress, the compliance was decreased. Thus acute sympathetic stimulation induced by CPT decreases the wall stiffness of human arteries in vivo. This may be explained by an unloading of stiffer wall components during active arterial constriction. PMID- 7864208 TI - Systemic and subcutaneous microvascular oxygen tension in conscious Syrian golden hamsters. AB - Arteriolar and venular oxygen tension distribution was studied in the subcutaneous connective tissue of the chamber window preparation in conscious Syrian golden hamsters as a function of the systemic PO2, PCO2, pH, arterial pressure and hematocrit, microvascular red blood cell (RBC) velocity, vessel diameter, and blood flow in the same microvessels. PO2 was measured with the phosphorescence decay technique using Pd-meso-tetra(4-carboxyphenyl)porphyrin (30 mg/kg body wt iv). Systemic arterial and venous PO2s were 71.6 +/- 13.1 and 28.4 +/- 5.1 mmHg, while oxygen tension was 45.1 +/- 13.3 mmHg in arterioles and 30.1 +/- 10.7 mmHg in venules. The relatively low arteriolar PO2 and the small arteriolar-venular PO2 gradient indicate that some blood oxygen exits directly to the tissue or is shunted before reaching the capillaries. RBC velocity was the strongest correlate of microvascular PO2 (arterial correlation coefficient = 0.503 and venous correlation coefficient = 0.560, P < 0.001). Microvascular PO2 was also correlated with blood flow, vessel diameter, blood pH, and PCO2 but not with systemic PO2. Arterial oxygen tension was only significantly related to PCO2, pH, and hematocrit. These findings suggest that oxygen delivery to the tissue improves with increasing blood flow velocity and that microvascular PO2 is a locally regulated parameter in the absence of major systemic perturbations. PMID- 7864209 TI - Starling resistor vs. distensible vessel models for embolic pulmonary hypertension. AB - We investigated whether the Starling resistor model (Mitzner et al. J. Appl. Physiol. 51: 1065-1071, 1981) or a distensible vessel model (Haworth et al. J. Appl. Physiol. 70: 15-26, 1991) best describes pulmonary vascular pressure-flow (Q) relationships in embolic pulmonary hypertension. Mean pulmonary arterial pressure (Ppa)-Q plots at constant left atrial pressure (Pla) and Ppa-Pla plots at constant Q were investigated in seven dogs before and after 500-micron glass bead pulmonary embolism. Embolization to a mean angiographic obstruction of 78% increased the slope and extrapolated pressure intercept (P(i)) of Ppa-Q plots and increased the inflection point of Ppa-Pla plots, above which an increase in Pla is transmitted to Ppa in a ratio of approximately 1:1. The Starling resistor and the distensible vessel model provided a reasonably good fit to the Ppa-Q and Ppa Pla coordinates before and after embolism. However, contrary to the prediction of the Starling resistor model, no correlation was found between the inflection point of Ppa-Pla plots and P(i). We therefore conclude that an increased closing pressure is unlikely to contribute to embolic pulmonary hypertension. PMID- 7864210 TI - Protection from pulmonary hypertension with an orally active endothelin receptor antagonist in hypoxic rats. AB - The aim of this study was to investigate the potential role of endothelin (ET) in the development of chronic hypoxic pulmonary hypertension. Pulmonary vascular reactivity to ET-1 was first examined in isolated perfused lungs from normoxic and chronically hypoxic rats in the presence of bosentan, a new nonpeptide mixed antagonist of ETA and ETB receptors. The effect of chronic treatment with bosentan was then examined in rats that were exposed to chronic hypoxia and developed pulmonary hypertension. In lungs from normoxic rats, bosentan (10(-5) M) abolished the vasodilator responses to ET-1 (10(-10) M) or to the ETB selective agonist IRL-1620 (10(-10) M) and attenuated the vasoconstrictor responses to 10(-9) M ET-1 (from 8.7 +/- 0.7 to 1.8 +/- 0.3 mmHg, P < 0.01) or 10(-9) M IRL-1620 (from 1.5 +/- 0.4 to 0.4 +/- 0.1 mmHg, P < 0.05). In lungs from chronically hypoxic rats, the pressor response to 3 x 10(-10) M ET-1 was abolished by bosentan and partially reduced by the selective ETA antagonist BQ 123. In conscious rats previously exposed to hypoxia for 15 days, pretreatment with bosentan (100 mg.kg-1.day-1 by gavage) for 3 days attenuated the increase in systemic arterial pressures and the concomitant decrease of cardiac output in response to an intravenous bolus of ET-1 (3 x 10(-10) M). In rats exposed to hypoxia for 15 days and simultaneously treated with bosentan, pulmonary arterial pressure was lower (P < 0.05) and right ventricular hypertrophy was less severe (P < 0.01) than in control hypoxic rats treated with vehicle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864211 TI - LV and myocyte structure and function after early recovery from tachycardia induced cardiomyopathy. AB - Left ventricular (LV) function and mass were measured in six conscious dogs at weekly intervals during the progression of tachycardia-induced dilated cardiomyopathy (DCM) and during a 1-mo recovery period from DCM (post-DCM). LV end-diastolic volume and LV wall stress increased and LV ejection fraction decreased with each week of pacing. Despite the increased LV wall stress, LV mass did not change during the progression of tachycardia DCM. One week post-DCM resulted in an improved LV ejection fraction and normalization of neurohormonal profiles. However, 1 wk post-DCM was accompanied by a 26% increase in LV mass and persistent LV chamber dilation. Isolated myocyte function was examined and compared with that in six normal control dogs. Myocyte percent and myocyte velocity of shortening were 19 and 32% lower, respectively, in the post-DCM group compared with controls. Thus termination of the tachycardia subsequent to the development of DCM resulted in persistent LV chamber dilation and abnormalities in myocyte contractile function. The improved LV pump function with early recovery from tachycardia-induced DCM was mediated by LV hypertrophy and a subsequent reduction in LV wall stress rather than a normalization of LV geometry and myocyte contractile function. PMID- 7864212 TI - Intrinsic cardiac enkephalins inhibit vagal bradycardia in the dog. AB - Met-enkephalin-Arg-Phe (MEAP) has been identified in acid extracts of canine heart tissue. The effects of synthetic MEAP on the vagal control of heart rate were investigated in anesthetized dogs. The arterial infusion of MEAP (3 nmol.min 1.kg-1) inhibited the bradycardia observed during electrical stimulation of the right vagus nerve by 72%. After the infusion was stopped, the responsiveness to vagal stimulation returned to normal, with a half-time between 2 and 3 min. The inhibition by MEAP was reversed by the high-affinity opiate antagonist diprenorphine (100 micrograms/kg). MEAP did not alter the negative chronotropic effect of the direct-acting muscarinic agonist methacholine. This observation suggested that MEAP exerted its effect at a site in the efferent vagal tract proximal to nodal muscarinic receptors. Increasing MEAP infusions (0.09-3.00 nmol.min-1.kg-1) produced a graded suppression of vagal bradycardia, with a half maximal effect near 0.3 nmol.min-1.kg-1. Met-enkephalin (ME) produced responses very similar to those obtained with MEAP. The effects of ME were also blocked by prior administration of diprenorphine. Dose responses to ME were shifted to the right of those for MEAP, and half-maximal responses for ME were obtained at two to four times the dose required for MEAP. The data suggest that the intrinsic cardiac enkephalin MEAP can regulate vagal control of heart rate at physiologically achievable concentrations and may serve as a local regulator of the parasympathetic-myocardial interface. PMID- 7864213 TI - cGMP mediates the desensitization to bradykinin in isolated canine coronary arteries. AB - The relaxation to bradykinin in canine coronary arteries is mediated by endothelium-derived nitric oxide (NO) and hyperpolarizing factor (EDHF). Desensitization to the kinin was induced by incubation of canine coronary arteries with endothelium with 10(-8) M bradykinin for 30 min. After washout, tissues were contracted with prostaglandin F2 alpha, and concentration-relaxation curves to bradykinin were obtained in control and desensitized arteries treated with indomethacin. After desensitization, there was a shift to the right of the concentration-relaxation curves to bradykinin. However, the elevation in guanosine 3',5'-cyclic monophosphate (cGMP) levels evoked by bradykinin was similar in both groups of tissues. The curves to bradykinin obtained in the presence of NG-nitro-L-arginine (an NO synthase inhibitor) were depressed, whereas those obtained in arteries contracted with potassium (to eliminate the EDHF-mediated relaxation) were not affected by the desensitization. Addition of NG-nitro-L-arginine, oxyhemoglobin, or methylene blue before the desensitization procedure preserved, whereas 3-morpholinosydnonimine (SIN-1, a donor of NO) and 8 bromoguanosine 3',5'-cyclic monophosphate impaired, the EDHF-mediated relaxation to bradykinin. Thus the selective impairment of the EDHF-dependent relaxation to bradykinin may be mediated by NO, acting mainly through increased production of cGMP. PMID- 7864214 TI - Hypoglycemia selectively abolishes hypoxic reactivity of pial arterioles in piglets: role of adenosine. AB - Episodes of hypoxia often occur in hypoglycemic newborns, but it is not known whether dysfunctions in cerebrovascular regulation contribute to brain injury incurred by these affected neonates. We tested the hypotheses that 1) perinatal hypoglycemia impairs cerebrovascular responses to hypoxia and 2) a reduced vascular smooth muscle sensitivity to adenosine accounts for this impairment. Responses of 25- to 50-mu m-diam pial arterioles were determined using the cranial window technique in isoflurane-anesthetized newborn piglets < 5 days of age. Hypoxia (arterial PO2 = 28 +/- 1 mmHg) caused a 47 +/- 5% increase (P = 0.0008) in arteriolar diameter, 89% of which could be blocked by prior superfusion of the window space with the preferential A2-adenosine receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX; 50 microM). Insulin-induced hypoglycemia (blood glucose = 18 +/- 1 mg/dl without isoelectric electroencephalogram) caused a 31 +/- 5% increase (P = 0.002) in arteriolar diameter; however, no additional dilatative response to hypoxia (arterial PO2 = 28 +/- 1 mmHg) could be elicited in these animals. Arteriolar dilation of 41 +/- 6% (P = 0.002) induced by superfusion of 20 microM adenosine under normoglycemic conditions was also completely abolished after the animals were rendered hypoglycemic. Unlike the response to hypoxia and adenosine, hypoglycemia only attenuated prostanoid-dependent dilations to hypercapnia (arterial PCO2 = 68 +/- 3 mmHg) by 55 +/- 9%. These results indicate that, in the newborn, hypoglycemia selectively abolishes hypoxic reactivity through an impairment in adenosine mediated cerebrovascular dilation. PMID- 7864215 TI - Dichloroacetate stimulates carbohydrate metabolism but does not improve systolic function in ischemic pig heart. AB - Increased carbohydrate utilization may protect the heart during ischemia and reperfusion. Dichloroacetate (DCA) stimulates pyruvate dehydrogenase, which is the rate-limiting step in oxidation of lactate and pyruvate. The purpose of this study was to determine if the myocardial metabolic changes induced by intracoronary DCA during myocardial ischemia were accompanied by improvement in systolic function. A perfusion circuit was created from the carotid to left anterior descending coronary artery (LAD) in 11 anesthetized Yorkshire swine. Data were obtained under strict hemodynamic control at baseline, after 15 min of moderate (30%) LAD flow reduction, and after an additional 15 min of ischemia with either intracoronary DCA (3 mM, n = 6) or saline (n = 5) infusion. DCA decreased lactate release and increased lactate uptake during ischemia as measured by glucose and lactate carbon-labeled tracers. Despite these metabolic changes, no improvement in systolic shortening, microsphere blood flow, or oxygen consumption occurred. Thus, although DCA stimulated carbohydrate metabolism during myocardial ischemia, it did not directly improve systolic function. PMID- 7864216 TI - Cholinergic and alpha-adrenergic coronary vasomotion [corrected] with increasing ischemia-reperfusion injury. AB - Ischemia-reperfusion-induced injury of the coronary vasculature could result in an attenuated vasodilator or increased vasoconstrictor tone that might impact on myocardial recovery and viability. In 30 open-chest dogs the left circumflex coronary artery was occluded for 15 or 60 min and then reperfused, and responses to intracoronary acetylcholine, the alpha 1-adrenergic agonist methoxamine, and the alpha 2-adrenergic agonist BHT-933 (n = 10 each) were measured. In the experiments with 60 min of occlusion, triphenyltetrazolium chloride (TTC) staining was used to distinguish reversibly (TTC+) and irreversibly (TTC-) injured myocardium. After 15 min of occlusion, the vasodilator response to acetylcholine was not altered but was significantly reduced in TTC+ subendocardium and midmyocardium after 60 min of occlusion and was further reduced in TTC- subendocardium, midmyocardium, and also in subepicardium. The vasoconstrictor responses to methoxamine and BHT-933 were not altered after 15 or 60 min of occlusion in both TTC+ and TTC- myocardium. Posterior wall thickening was not affected by acetylcholine, methoxamine, or BHT-933. Thus, in reversibly injured myocardium after 15 min of occlusion, cholinergic and alpha-adrenergic coronary vasomotor responses are unchanged. With increasing duration of ischemia, reversibly and even more so irreversibly injured reperfused myocardium are characterized by an impaired cholinergic coronary vasodilation but not an enhanced alpha-adrenergic coronary vaso-constriction. PMID- 7864217 TI - A model of combined feedforward and feedback control of coronary blood flow. AB - Recent evidence shows that norepinephrine affects coronary blood flow not only by alpha-receptor-mediated vasoconstriction and by feedback metabolic vasodilation that occurs as a result of myocardial beta-receptor activation, but also by the direct activation of coronary vascular beta-receptors that increase flow in a feedforward manner. The implications of combined feedforward and feedback control in maintaining the balance between metabolism and flow were investigated in the present mass balance model. Feedback was represented by a closed loop and was based on the hypothesis that the regulated variables are myocardial PO2 and PCO2 and that divergence of these variables from their operating point values functions as the metabolic error signals that manipulate coronary vascular smooth muscle and flow to match metabolism. alpha-Receptor-mediated vasoconstriction and beta-receptor-mediated vasodilation are represented by feedforward open loops that are activated simultaneously with increases in metabolism. The postulated control schemes of 1) metabolic feedback control alone, 2) feedback plus alpha- and beta-adrenergic feedforward control, and 3) feedback plus beta-adrenergic feedforward control were able to simulate the steady-state increase in coronary flow and the decrease in coronary venous PO2 that occurs during comparable experimental conditions. The simulations demonstrate that 1) the speed and accuracy of the flow response improve as beta-adrenergic feedforward control is added and alpha-adrenergic feedforward control is removed from the control scheme, 2) high feedback gain also improves the accuracy of the flow response, but the penalty is instability, and 3) a lag in alpha-adrenergic feedforward control improves the stability of the coronary response. PMID- 7864218 TI - In vivo differentiation of leukocytes rolling in mesenteric postcapillary venules. AB - A method is presented to assess in vivo in transparent tissues the leukocyte subtypes that roll in microvessels. In nine rabbits anesthetized with ketamine xylazine, leukocyte nuclei were stained in situ with acridine yellow (3 mg/kg i.v. for 5 min). Intravital fluorescence video microscopy in 24 mesenteric venules (17-29 microns, median 21) indicated labeling of all rolling leukocytes. On the basis of the shape of their nucleus, 67-100% (median 89) could be classified unequivocally (13-366 cells analyzed, median 77) as polymorphonuclear (PMN, i.e., granulocytes) or monomorphonuclear (lymphocytes and monocytes). Of these classified cells, 94-100% were PMNs (median 100, including 1 stray value of 69%). This PMN percentage was independent of the level of leukocyte rolling (2 36/min, median 14), vessel diameter, flow velocity (0.5-2.5 mm/s), or duration of the experiment (< 6 h). The dye had no significant influence on hemodynamic parameters, systemic leukocyte counts (1.5-7.8 x 10(9)/l), or in vitro differentiation pattern (27-38% granulocytes, 0-2% monocytes, 61-71% lymphocytes). In conclusion, our method demonstrated that the leukocytes that roll in postcapillary venules of the exteriorized rabbit mesentery are almost exclusively granulocytes. PMID- 7864219 TI - Effects of sarcoplasmic reticulum Ca2+ load on the gain function of Ca2+ release by Ca2+ current in cardiac cells. AB - We studied the effects of variable sarcoplasmic reticulum (SR) Ca2+ loading on changes in the gain index of Ca2+ release from the SR, measured as the ratio of the amount of Ca2+ released to the magnitude of the Ca2+ current (ICa) integrated for the initial 20 ms of the depolarization, in whole cell voltage-clamped rat ventricular myocytes dialyzed with the Ca2+ indicator indo 1 salt at 23 degrees C. Changes in ICa were measured directly, and changes in the SR Ca2+ release were indexed by changes in the amplitudes and rates of rise of cytosolic Ca2+ (Ca2+i) transients. The SR Ca2+ load was graded by the duration of conditioning voltage clamp steps and verified by caffeine-dependent Ca2+i transients. A train of abbreviated (from 100 to 20 ms) voltage-clamp depolarizations, which triggers SR Ca2+ release but fails to replenish the SR with Ca2+, diminished the SR Ca2+ load by 56 +/- 5%, did not alter peak ICa but reduced the amplitudes of the ICa dependent Ca2+i transients by 52 +/- 3%, and decreased the gain index by 60 +/- 3% (SE; n = 5 or 6). Changes in the amplitudes of Ca2+i transients elicited by ICa and changes in the gain index were linearly correlated (r2 = 0.83 and 0.79, respectively; P < 0.001 for each) with changes in amplitudes of Ca2+i transients elicited by caffeine pulses applied in lieu of the respective voltage-clamp pulses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864220 TI - Presence and secretion of atrial natriuretic peptide from cultured human aortic endothelial cells. AB - The endothelium is the production site of several potent vasoactive substances that modulate vascular tone and growth. The present study was undertaken to investigate the presence and secretion of atrial natriuretic peptide (ANP) immunoreactivity from vascular endothelial cells. ANP immunoreactivity was present in cultured human aortic endothelial cells by both immunohistochemical staining and radioimmunoassay. ANP immunoreactivity was also detectable in culture medium from human aortic endothelial cells in low picogram concentrations. These findings suggest that vascular endothelium is a site of ANP production and secretion of ANP. There was a differential distribution of ANP and endothelin-1 (ET-1), with a higher ANP concentration in cell extracts and a higher ET-1 concentration in cell culture media. Although ANP has been conceived as a circulating endocrine hormone, these findings are consistent with ANP functioning also as an autocrine and paracrine modulator in the regulation of vascular tone and growth. PMID- 7864221 TI - Phosphorylation by protein kinase A enhances delayed rectifier K+ current in rabbit vascular smooth muscle cells. AB - The effect of adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) activity on 4-aminopyridine (4-AP)-sensitive delayed rectifier current (IdK) in isolated rabbit portal vein smooth muscle cells was studied via whole cell voltage clamp (20-22 degrees C). A threefold increase in 4-AP-sensitive (5 mM) IdK was recorded after gaining cell access during dialysis with 5 mM intracellular ATP and internal Ca2+ buffered to a low level with 5 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Dialysis with the nonhydrolyzable ATP analogue 5'-adenylylimidodiphosphate (5 mM) or the specific peptide inhibitor of PKA (PKI; 10 microM) reduced current runup by 50 and 70%, respectively. Delayed dialysis with PKI reversed runup and inhibited IdK to below initial levels. Forskolin (1 microM) caused a reversible increase in IdK, which was inhibited by 4-AP (5 mM). Isoproterenol (1 microM) reversibly enhanced IdK; the increase was sensitive to propranolol (2 microM) and 4-AP (5 mM) and was prevented by dialysis with PKI (10 microM). IdK was enhanced over the entire voltage range of activation and associated with a negative shift in reversal potential of net whole cell current, consistent with hyperpolarization of resting membrane potential. The data provide the first evidence for a signal transduction mechanism involving beta-adrenoceptors, adenylate cyclase, and a phosphotransferase reaction mediated by PKA for the regulation of delayed rectifier K+ channels in vascular smooth muscle. PMID- 7864222 TI - Oxygen, glucose, and lactate uptake by fetus and placenta during prolonged hypoxemia. AB - Our aim was to compare the effects of short (4 h) and prolonged (24 h) periods of reduced uterine blood flow (RUBF) on fetal and placental uptake of O2, glucose, and lactate. In pregnant sheep, uterine and umbilical blood flows were measured under normal conditions and after 4 and 24 h of RUBF. A 50% reduction in uterine blood flow caused a 56% reduction in fetal arterial O2 saturation (SaO2). Umbilical blood flow increased from 325 +/- 33 to 378 +/- 32 ml.min-1.kg-1 (P < 0.05) after 4 h but was not different from pre-RUBF values after 24 h. O2 uptake by the gravid uterus was not altered by RUBF, due to an increase (84%) in uterine O2 extraction. Similarly, uteroplacental and fetal O2 consumptions and fetal glucose uptake were not affected by RUBF, whereas uteroplacental glucose uptake was significantly reduced after 4 h (by 42%) and 24 h (by 58%) of RUBF. Fetal lactate uptake was greatly reduced from 78.7 +/- 15.5 to -167 +/- 57 mumol.min 1.kg-1 after 4 h and to -198 +/- 80 mumol.min-1.kg-1 after 24 h of RUBF; negative values indicate placental lactate uptake from the fetal circulation. Thus, although RUBF significantly reduced fetal SaO2, fetal and uteroplacental O2 consumptions did not change. In addition, although fetal glucose uptake was not altered by RUBF, during RUBF the placenta became a major site of lactate clearance from the fetal circulation. PMID- 7864223 TI - Role of renal medullary blood flow in the development of L-NAME hypertension in rats. AB - The effect of chronic intravenous infusion of the nitric oxide inhibitor NG-nitro L-arginine methyl ester (L-NAME; 8.6 mg.kg-1.day-1) on blood pressure, intrarenal blood flow distribution, and sodium and water balance was studied in conscious rats. On the 1st day of intravenous L-NAME infusion, renal medullary blood flow was reduced by 22%, renal cortical blood flow was unaltered, approximately 1 meq of sodium and 12 ml of water were retained, and blood pressure increased from 96 +/- 2 to 118 +/- 2 mmHg. Medullary blood flow was maintained at this decreased level, sodium continued to be retained, body weight continued to increase, and blood pressure remained elevated for the 5 days of L-NAME infusion. During the postcontrol period, blood flow in the renal medulla returned to levels not significantly different from control; the animals went into negative sodium balance and stopped gaining weight, and blood pressure returned to control. The present experiments indicate that decreased renal medullary blood flow and retention of sodium and water play an important role in the development of hypertension during chronic systemic L-NAME administration despite no measurable changes in renal cortical blood flow. PMID- 7864224 TI - Altered vagal and sympathetic control of heart rate in left ventricular dysfunction and heart failure. AB - We investigated alterations in autonomic control of heart rate in conscious dogs with left ventricular (LV) dysfunction in the presence and absence of heart failure (HF) due to rapid pacing. In dogs with LV dysfunction but no HF, indexes of parasympathetic control decreased significantly after only 4 days of pacing. In dogs with fully developed HF, both vagal and sympathetic contributions were small. Vagomimetic doses of atropine increased both R-R interval (419 +/- 25 to 466 +/- 34 ms, P < 0.05) and standard deviation (SD) of the R-R interval (13 +/- 2 to 34 +/- 9 ms, P < 0.05). The digitalis glycoside deslanoside (Cedilanid-D) alone prolonged R-R interval (420 +/- 33 to 492 +/- 44 ms, P < 0.01) and tended to increase SD (14 +/- 4 to 28 +/- 8 ms, P = 0.08). After Cedilanid-D, low-dose atropine resulted in no significant further change in R-R interval or SD. These data indicate that changes in vagal control of heart rate become apparent at a very early developmental stage of LV dysfunction, and we speculate that this may provide important prognostic information in patients who are at risk for developing progressive myocardial dysfunction and HF. PMID- 7864225 TI - Pressor-induced responses of the cat ventral medullary surface. AB - We examined ventral medullary surface activity using light reflectance procedures after blood pressure alterations induced by phenylephrine or sodium nitroprusside in 23 pentobarbital sodium-anesthetized cats. Images of reflected 660-nm light were collected and digitized at 1- to 3-s intervals after baseline and intravenous saline, 5-40 micrograms/kg phenylephrine, or sodium nitroprusside infusion. Carotid sinus nerve denervation (CSD) and bilateral vagotomy were performed in five and three animals, respectively, and challenges were repeated. Phenylephrine elicited a dose-dependent transient blood pressure elevation and reflectance increase (interpreted as activity decline) over the entire ventral medullary surface examined. The increase consisted of an initial rapid transient component, peaking at 45 s, and a 3- to 5-min recovery. CSD enhanced, and vagotomy substantially reduced, the initial transient response to phenylephrine. Sodium nitroprusside-induced lowering of blood pressure was associated with decreased reflectance in rostral sites and increased reflectance in caudal regions. CSD abolished a late component and diminished amplitude of an initial rapidly rising component of changes induced by nitroprusside, a decline further accentuated by addition of vagotomy. PMID- 7864226 TI - Glutamine and glucose metabolism in enterocytes of the neonatal pig. AB - Glutamine and glucose metabolism was studied in 0- to 21-day-old pig enterocytes. Cells were incubated at 37 degrees C for 30 min in Krebs-Henseleit bicarbonate buffer (pH 7.4) in the presence of 2 mM [U-14C]glutamine with or without 5 mM glucose, or 5 mM [U-14C]glucose with or without 2 mM glutamine. Glutamine was metabolized to ammonia, glutamate, alanine, aspartate, CO2, citrulline, ornithine, and proline, whereas glucose was converted to lactate, pyruvate, and CO2 in pig enterocytes. CO2 production from glutamine accounted for 32-36% and 3 4% of utilized glutamine carbons in 0- to 7-day-old and 14- to 21-day-old pigs, respectively. The rates of O2 consumption and metabolism of glutamine and glucose decreased in enterocytes from 2- to 14-day-old pigs compared with 0-day-old pigs. By day 14 after birth, the oxidation of glutamine and glucose as well as citrulline production had decreased by 90-95%. Arginine synthesis from glutamine occurred in cells from 0- to 7-day-old pigs but not 14- to 21-day-old ones. Glucose (5 mM) had no effect on glutamine utilization and oxidation or the production of glutamate and arginine but stimulated the formation of alanine, citrulline, and proline at the expense of aspartate. In contrast, glutamine (2 mM) inhibited glycolysis and glucose oxidation in cells from 0- to 7-day-old pigs and had no effects in 14- to 21-day-old pigs. As a result, glutamine contributed approximately 2-fold greater amounts of ATP to 0- to 7-day-old pig enterocytes than glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864227 TI - Fetal responses to carotid occlusion: immaturity of buffering systems. AB - In postnatal animals, carotid occlusion does not stimulate reflex hormonal responses, because decreases in carotid arterial baroreceptor activity are balanced by reflex-mediated increases in vagal afferent traffic from aortic and cardiac receptors. The present experiments were designed to test the hypothesis that hormonal responses to carotid occlusion in fetal animals are not inhibited by vagal afferents. In thirteen chronically catheterized fetal sheep (125-146 days), bilateral carotid occlusion (n = 11) increased arterial blood pressure from 44.0 +/- 2.4 to 55.2 +/- 3.3 mmHg, decreased heart rate from 189 +/- 5 to 165 +/- 12 beats/min, increased plasma adrenocorticotropin from 71 +/- 15 to 248 +/- 79 pg/ml and vasopressin from 3.0 +/- 1.0 to 7.4 +/- 2.6 pg/ml but did not significantly alter renin. Plasma hormone concentrations were not significantly altered in control (n = 7) experiments or in response to unilateral carotid occlusion (n = 4). The results of these experiments demonstrate the functional immaturity of the vagal afferent buffering systems in the late-gestation fetus compared with the postnatal animal. PMID- 7864228 TI - Adaptive resetting of the volume control of vasopressin secretion during sustained hypovolemia. AB - To determine the effect of sustained hypovolemia on vasopressin secretion, we studied rats after 1-32 h of diuretic therapy. We found that an injection of furosemide (10 mg/kg) produced a transient marked increase in urine output, a moderate 7-10% reduction in blood volume, and a three- to fourfold rise in plasma vasopressin from 1.6 +/- 0.2 to 5.6 +/- 1.0 pmol/l. When the hypovolemia was maintained by repeated injections of the diuretic, plasma vasopressin remained elevated for > or = 8 h but returned almost to normal by 32 h, even though plasma electrolytes, blood pressure, hematocrit, and the other measures of hypovolemia were unchanged. At this time, pituitary vasopressin was undiminished, and plasma vasopressin rose normally or even supranormally when an acute hypovolemic or osmotic stimulus (intraperitoneal polyethylene glycol or hypertonic saline) was superimposed. However, the lines describing the relationship of log plasma vasopressin to plasma volume and plasma sodium in the rats treated with furosemide for 32 h lay to the left of the same relationships in the rats treated for 8 h or the sham-treated controls. We conclude that, in rats, the vasopressin response to sustained hypovolemia persists for > or = 8 h but is markedly diminished by 32 h. The decline in plasma vasopressin during this interval appears to be due to adaptive resetting of the volume control mechanism. PMID- 7864229 TI - DDAVP-induced maternal hyposmolality increases ovine fetal urine flow. AB - Fetal urine flow is influenced by fetal intravascular volume, glomerular filtration rate, tubular reabsorption, and fluid regulatory hormones. As maternal to-fetal fluid transfer is dependent on hydrostatic and osmotic gradients, we postulated that a chronic decrease in maternal plasma osmolality would promote transplacental fluid transfer and increase fetal urine flow. Six pregnant ewes and singleton fetuses (131 +/- 2 days; term = 150 days) received bladder and hindlimb arterial and venous catheters. After 5 days, plasma and urine composition, urine flow rate (Uvol), and plasma arginine vasopressin (AVP) levels were measured during a 2-h control period. At 2 h, tap water (2 liter, 38 degrees C) was administered to the ewe. At 3 h, ewes received a 20-micrograms bolus of 1 desamino-[D-Arg8]vasopressin (DDAVP), followed by continuous infusion (4 micrograms/h). In response to water loading, maternal urine osmolality decreased (761 +/- 158 to 339 +/- 13 mosmol/kgH2O), and Uvol increased. After DDAVP, maternal urine osmolality increased (1,270 +/- 89 mosmol/kgH2O), and Uvol, hematocrit, plasma osmolality (304 +/- 1 to 284 +/- 4 mosmol/kgH2O), and protein concentration decreased. Five hours after maternal DDAVP infusion, fetal plasma osmolality decreased (300 +/- 1 to 281 +/- 3 mosmol/kgH2O), and Uvol increased (0.4 +/- 0.1 to 1.3 +/- 0.2 ml/min) and remained elevated at 24 h. There was no change in fetal plasma DDAVP (immunoreactive AVP) levels or fetal urine osmolality. Controlled changes in maternal plasma osmolality may prove useful in modulating fetal urine flow and, ultimately, amniotic fluid volume. PMID- 7864230 TI - TxA2 receptor activation elicits organ-specific increases in microvascular permeability in the rat. AB - We investigated whether the stable thromboxane A2 (TxA2) analogue U-46619 had any direct effect on extracellular fluid partition. In anesthetized open-chest rats, U-46619 (1.25 and 20 micrograms/kg iv) dose dependently increased mean pulmonary arterial pressure and hematocrit, whereas mean systemic arterial pressure was raised only at the low dose of agonist. The increase in hematocrit (13.2 +/- 2.9% at 20 micrograms/kg; P < 0.05) still occurred in bilaterally nephrectomized rats and in binephrectomized plus splenectomized rats (11.6 +/- 2.7 and 12.2 +/- 4.6%, respectively; both P = NS vs. U-46619 in control rats), corresponding to a calculated decrease in plasma volume of 22.1 +/- 4.5, 19.6 +/- 4.0, and 19.2 +/- 5.8%, respectively. Plasma protein concentration increased less than hematocrit, and the coefficient of reflection was significantly lower in these groups, suggesting protein extravasation. Additional experiments showed that U-46619 (1.25 and 10 micrograms/kg iv) dose dependently increased the vascular leak of albumin mainly in lung, kidneys, and spleen but not in brain, liver, mesentery, and cardiac and skeletal muscles. Pretreatment with the TxA2 receptor antagonist SQ-29,548 (2.5 mg/kg iv bolus plus 2.5 mg.kg-1.h-1 as maintenance) abolished all effects of U-46619, including the increase in mean pulmonary arterial pressure, hematocrit, plasma protein concentration, and albumin extravasation and the decrease in mean systemic arterial pressure, plasma volume, and coefficient of reflection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864231 TI - Systemic hemodynamics and renal function during long-term pathophysiological increases in circulating endothelin. AB - Although recent studies have reported endogenous plasma endothelin levels to be elevated two- to fivefold in chronic pathophysiological states, whether such an increase in circulating endothelin levels alone can lead to significant long-term alterations in cardiovascular and renal function is not known. The purpose of this study was to examine the long-term systemic hemodynamic and renal effects of a pathophysiological increase in plasma endothelin concentration in chronically instrumented, conscious dogs (n = 7). Infusion of endothelin-1 (2.5 ng.kg-1.min 1) for 8 days increased plasma concentration of immunoreactive endothelin approximately two- to threefold from 6.7 +/- 0.4 to 16.0 +/- 2.2 pg/ml. Mean arterial pressure increased 21% from a control value of 86.7 +/- 2.1 to 105.0 +/- 2.5 mmHg during the endothelin infusion period. Cardiac output averaged 2,200 +/- 205 ml/min during control and fell by 33% on day 4 of endothelin infusion (1,484 +/- 146 ml/min) and was still 14% below control after day 8 of endothelin infusion (1,885 +/- 154 ml/min). Endothelin increased total peripheral resistance from 42.0 +/- 3.1 to 80.3 +/- 9.1 mmHg.l-1.min. Increasing plasma endothelin two- to threefold was associated with an increase in renal vascular resistance and decreases in glomerular filtration rate and renal plasma flow. Endothelin-1 had no long-term effect on plasma renin activity or aldosterone concentration. These data indicate the importance of pathophysiological levels of endothelin in controlling renal and cardiovascular function in chronic conditions. Furthermore, the results indicate that endothelin may play a role as a mediator of chronic hypertension in pathophysiological states associated with endothelial dysfunction. PMID- 7864232 TI - Assessment of spontaneous baroreflex sensitivity in rats a new method using the concept of statistical dependence. AB - A new method was developed to evaluate the cardiac baroreflex sensitivity (BRS) from spontaneous mean arterial pressure (MAP) and heart rate (HR) changes in conscious rats. It relies on the determination of the statistical dependence between MAP and HR values. In 13 control rats, 12 rats with a pharmacologically induced hypertension, and 7 rats with a chronic sinoaortic denervation (SAD), dependent (MAP, HR) couples related to the baroreflex activity were selected to determine the spontaneous BRS (Sp-BRS). In control and hypertensive rats, pharmacological BRS (Ph-BRS) was estimated using graded bolus intravenous doses of vasoactive drugs. Ph-BRS was significantly lower in hypertensive than in control rats. Sp-BRS was determined in 10 control and 10 hypertensive rats and was strongly correlated with Ph-BRS (r = 0.83, n = 20, P < 0.0001). Sp-BRS could be evaluated in six SAD rats and was profoundly decreased (-86%, P < 0.001) compared with control rats. In conclusion, this work validates the estimation of the cardiac BRS from spontaneous MAP and HR variations with use of (MAP, HR) couples of values that are statistically dependent. PMID- 7864233 TI - Reduced norepinephrine turnover in organs and brains of obesity-prone rats. AB - One-half of the adult male Sprague-Dawley rats fed a diet relatively high in fat, sucrose, and energy content (HE diet) develop diet-induced obesity (DIO). The rest are diet resistant (DR). The role of peripheral and central norepinephrine (NE) activity in predisposing them to these weight gain patterns was assessed before HE diet exposure. Chow-fed male 3-mo-old Sprague-Dawley rats were separated as being prone to become DIO or DR by their high (3.06 +/- 0.14 micrograms) vs. low (1.17 +/- 0.10 micrograms; P = 0.001) 24-h urine NE output, respectively. Turnover of NE, an index of sympathetic activity, was assessed by synthesis inhibition with alpha-methyl-p-tyrosine. DIO-prone rats had significant 53 and 18% reductions in heart and pancreas NE turnover, with interscapular brown adipose tissue turnover comparable to that of DR-prone rats. Hypothalamic NE turnover was significantly decreased by 85 and 60% in the ventromedial nucleus and lateral area vs. DR-prone rats. Although present in DR-prone rats, no turnover was found in the dorsomedial nucleus of DIO-prone rats. Endogenous NE was reduced by 28% in the paraventricular nucleus, whereas arcuate/median eminence turnover was increased by 100% in DIO-prone rats. Amygdalar NE turnover was similar between phenotypes. These intrinsic differences in NE metabolism may play an important role in the development of DIO on HE diets. PMID- 7864234 TI - Chronic endothelin-induced pressor and renal actions in conscious dogs do not require altered ANG II formation. AB - Plasma endothelin levels are elevated approximately two- to threefold in a number of chronic pathophysiological conditions associated with hypertension. Results from recent studies indicate an important interaction between endothelin and the renin-angiotensin system (RAS). The role of the RAS in mediating the increases in arterial pressure produced by long-term pathophysiological elevations in circulating levels of endothelin is unknown. Therefore, the purpose of this study was to chronically increase circulating levels of endothelin within the pathophysiological range and determine the long-term cardiovascular and renal actions of endothelin in control dogs (n = 6) and in dogs pretreated with a converting-enzyme inhibitor (CEI) (n = 6) or CEI + angiotensin II (ANG II) replacement (n = 6). Infusion of endothelin-1 for 8 days at a rate of 2.5 ng.kg 1.min-1 increased plasma endothelin from 7.1 +/- 0.9 to 19.8 +/- 3.3 pg/ml. In control dogs, endothelin increased mean arterial pressure (MAP) by 19% (90 +/- 2 to 107 +/- 3 mmHg) while decreasing renal blood flow (RBF) by 30% and glomerular filtration rate (GFR) by 15-20%. Long-term elevation of circulating endothelin produced similar elevations in MAP in dogs pretreated with CEI (+16%) or CEI + ANG II (+17%). Similar decreases in RBF and GFR also occurred in response to endothelin in all three groups. These results indicate that although long-term increases in circulating endothelin within the pathophysiological range produce significant increases in arterial pressure, this effect does not appear to be mediated by the RAS. PMID- 7864235 TI - Modulation of intrinsic cardiac neuronal activity by nitric oxide donors induces cardiodynamic changes. AB - Studies were performed to determine 1) whether a specific marker for nitric oxide production is associated with canine intrinsic cardiac neurons, 2) whether the transmembrane properties of these neurons can be altered by nitric oxide donors, 3) whether in situ intrinsic cardiac neurons are sensitive to nitric oxide donors, and 4) whether these neurons are involved in cardiac regulation. Thirty to forty percent of canine intrinsic cardiac neurons were labeled with a selective anatomic marker for nitric oxide production. Nitric oxide donors modified the transmembrane properties of a subpopulation of intrinsic cardiac neurons studied in vitro. The nitric oxide donors nitroglycerine, sodium nitrite, and nitroprusside induced concentration-dependent increases in neuronal activity frequently associated with cardiac augmentation. Similar neuronal responses were elicited by N-methyl-D-aspartate receptor activation as well as when the precursor of nitric oxide, L-arginine, and the exogenous nitric oxide donor, S nitroso-N-acetylpenicillamine, were administered, indicating that intrinsic cardiac neurons can be modulated by nitric oxide donors. Such neurons apparently are tonically influenced by locally released nitric oxide as local administration of the competitive inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester, suppressed their spontaneous activity. These data indicate that a significant population of nitric oxide-sensitive neurons exists in the canine intrinsic cardiac nervous system that are involved in cardiac regulation. PMID- 7864236 TI - Osmoregulatory modulation of thermal sweating in humans: reflex effects of drinking. AB - To gain better insight into the interaction between thermoregulation and osmoregulation, we examined the thermal sweating response to drinking in cell dehydrated humans. Cell dehydration (CDH) was induced by infusion of a 3% NaCl solution, at 1.2 ml/kg, for 2 h; infusion of a 0.9% NaCl solution in a separate experiment served as a control (euhydrated condition, EH). After infusion, subjects were heated by immersion of the lower legs in 42 degrees C water at an ambient temperature of 28 degrees C for 90 min. Subjects drank 4.3 ml/kg of H2O (approximately 38 degrees C) at 60 min of heating. The 3% NaCl infusion increased plasma osmolality by 13.6 +/- 0.8 mosmol/kgH2O and plasma arginine vasopressin concentration ([AVP]) by 3.3 +/- 0.7 pg/ml. Neither variable was altered with 0.9% NaCl infusion. Before drinking, esophageal temperature (Tes) had increased by 0.91 +/- 0.08 degrees C in CDH and by 0.40 +/- 0.11 degrees C in EH. Local chest sweating rate (SRch) had increased by 0.67 +/- 0.08 and 0.63 +/- 0.07 mg.min-1.cm-2 in CDH and EH, respectively. Thus the change in SRch per unit rise in Tes was much lower in CDH than in EH. Drinking immediately increased SRch and reduced Tes in CDH, with a reduction in plasma [AVP] and thirst rating. Drinking did not change thermoregulatory and osmoregulatory responses in EH. These results suggest that the act of drinking itself eliminates, at least partially, an osmotic inhibitory input to the thermoregulatory center, as well as osmotic AVP secretion and thirst. PMID- 7864237 TI - Neuropeptide Y fails to increase intraoral intake in rats. AB - Neuropeptide Y (NPY) has a potent orexigenic effect when administered either into the third ventricle or directly into hypothalamic nuclei, but the mechanism by which NPY increases intakes is poorly understood. The present study tested the ability of NPY to increase intake of the rat in the intraoral intake test, which focuses on the highly stereotyped consummatory phase of ingestion by introducing a 0.1 M sucrose solution directly into the oral cavity of rats via indwelling intraoral cannulas. Doses of 3, 9.5, and 30 micrograms of NPY, when administered into the third ventricle, all failed to change intraoral intake compared with a saline control. Food deprivation (24 h), however, nearly doubled intraoral intake. Additionally, in separate experiments, 9.5 micrograms of NPY significantly increased both 1-h food intake and 1-h bottle intake of 0.1 M sucrose. These results are consistent with two conclusions. 1) NPY does not affect the consummatory phase of ingestion. 2) NPY administration does not completely mimic the stimulus state associated with food deprivation, since food deprivation but not NPY administration increases intake in the intraoral intake test. PMID- 7864238 TI - Neuronal inhibition by a GABAB receptor agonist in the rostral ventrolateral medulla of the rat. AB - We recorded the effects of the gamma-aminobutyric acid class B (GABAB) receptor agonist baclofen on neuronal activity in the rat rostral ventrolateral medulla (RVLM) in tissue slices and in vivo. In vitro, baclofen (3 microM) produced hyperpolarization (13 of 17), decrease in input resistance (12 of 16), and reduction of spontaneous synaptic activity (7 of 14). Baclofen inhibited 84 of 87 spontaneously active neurons recorded extracellularly in vitro. Inhibition was concentration dependent (0.1-3 microM, maximum inhibition: 94 +/- 4%, n = 16) and persisted in low-Ca2+/high-Mg2+ medium (n = 19). The GABAB receptor antagonists CGP-54626A (1 microM, n = 19), CGP-55845A (1 microM, n = 15), and 2 hydroxysaclofen (0.5 mM, n = 3) attenuated inhibition by baclofen (1-3 microM) but not by muscimol or GABA. In vivo, iontophoresis of baclofen inhibited 31 of 32 RVLM neurons, including bulbospinal barosensitive (15 of 16) and respiratory ones (7 of 7). CGP-55845A attenuated baclofen inhibition (6 of 9). Bicuculline attenuated the effect of GABA but not that of baclofen (4 of 4). In summary, RVLM presympathetic neurons have somatodendritic GABAB receptors that may contribute to baclofen-induced hypotension in humans. PMID- 7864239 TI - Salivary secretion in cat submandibular gland mediated by chorda tympani afferents. AB - The aim of the present study was to investigate whether the afferent traffic from the tongue mediated only via the chorda tympani nerve (CTN) can still elicit reflex salivary and vasodilator responses in the cat submandibular gland (SMG) after section of the lingual nerve proper (LNP). Electrical stimulation of the chorda lingual nerve (CLN) at a site approximately 5 mm distal to the intersection of the CLN and the SMG duct elicited salivary and vasodilator responses in the SMG in sympathectomized cats. Both responses were unaffected by section of the LNP. The optimal frequency of CLN stimulation for submandibular salivation and vasodilation was 20 Hz, regardless of whether the LNP had been cut. Prior treatment with the autonomic ganglion blocker hexamethonium (10 mg/kg iv) virtually abolished the salivation and the blood flow increase in SMG. Prior treatment with scopolamine (0.1 mg/kg iv) almost abolished the salivary secretions but had no effect on the vasodilator responses in the SMG elicited by CLN stimulation after LNP section. The mechanism underlying the reflex submandibular salivation mediated by chorda tympani afferents appears to involve parasympathetic muscarinic receptors, but the mechanism for the vasodilator response has yet to be established. These results indicate that afferent traffic passing through the CTN on CLN stimulation is importantly involved in the parasympathetic reflex secretory and vasodilator responses in the cat SMG. PMID- 7864240 TI - Rates of glucose utilization in brain of active and hibernating ground squirrels. AB - Rates of glucose utilization (CMRGlc) were determined in some cerebral structures of active warm- and cold-adapted ground squirrels and hibernating ground squirrels with [14C]deoxyglucose (DG) by direct chemical measurement of precursor and products in samples dissected from funnel-frozen brain. The rate of supply relative to demand of glucose and [14C]DG in brain of hibernating animals was similar to or greater than that of controls. [14C]DG cleared from the plasma in hibernators much more slowly than in active animals, and the level of unmetabolized [14C]DG in brain and the integrated specific activity of the precursor pool in plasma exceeded those of the active animals by 4- to 10-fold. At 45 min after an intravenous pulse of [14C]DG, the unmetabolized [14C]DG remaining in the brains of the hibernators accounted for approximately 96% of the total 14C compared with approximately 10-15% in the active animals. The value of lambda, a factor contained in the lumped constant of the operational equation of the [14C]DG method, was estimated for each animal and found to be relatively constant over the sixfold range of glucose levels in the brains of all animals. Calculated CMRGlc in squirrels in deep hibernation was only 1-2% of the values in active animals. PMID- 7864241 TI - Vasodilation evoked from medulla and cerebellum is coupled to bursts of cortical EEG activity in rats. AB - Cerebral blood flow (rCBF), measured by laser-Doppler flowmetry, spontaneously fluctuates at approximately 6 events/min in the anesthetized rat. These cerebrovascular waves (CWs) are preceded by simultaneous and synchronous bursts of electrocorticographic activity similar to burst-suppression/spindle-burst electroencephalogram patterns. Identical burst-CW complexes are evoked by single electrical pulses of specific sites in the cerebellar fastigial nucleus or rostral ventrolateral medulla. These consist, sequentially, of a constant initial triphasic (positive-negative-positive) potential reversing polarity in lamina V, variable afterbursts, and transient elevations of rCBF appearing approximately 1.2 s after burst onset. Evoked bursts are occluded by spontaneous bursts appearing < 50 s earlier. Procainization of the cortex reversibly blocks burst-CW complexes. Gradually increasing stimulus frequency proportionally increases the numbers of burst-CW complexes before rCBF rises. We conclude that spontaneous and evoked burst-CW complexes result from excitation of common neurons in lamina V. These intracortical "vasodilator" neurons are spontaneously excited by thalamocortical afferents generating burst-suppression electroencephalogram (EEG) patterns and excited reflexively by afferent signals from the fastigial nucleus or rostral ventrolateral medulla and couple intrinsic neuronal activity to local vascular mechanisms generating vasodilation. PMID- 7864242 TI - Seasonal variations of capillary hydraulic conductivity and volume status. AB - The purpose of this study was to determine whether circulating plasma protein concentration, capillary hydraulic conductivity (Lp), and overall volume status in frogs were correlated and whether these correlations varied with season. Individual vessel Lp was thus examined on a monthly basis and correlated with changes in protein content in three body compartments (blood, lymph, and body cavity) over a 10-yr period. The frogs were anesthetized, blood and fluid samples collected, Lp assessed, and samples assayed for overall protein content. Volume status indicators varied cyclically over the course of 1 yr. Protein levels reached their peak in winter and were lowest in summer for all compartments. Lp for venular and arteriolar capillaries reached maximal levels in summer and fell steadily throughout the remainder of the year. Basal true capillary Lp was stable over the course of the year. Lp and total protein concentration were inversely proportional to each other on a seasonal basis but did not correlate on a monthly basis. Therefore, we conclude that the lack of a simple relationship between Lp and volume status suggests an independent driver such as a hormonal signal for the hydraulic conductivity. PMID- 7864243 TI - Muscarinic stimulation maintains in vivo insulin secretion in response to glucose after prolonged hyperglycemia. AB - Prolonged hyperglycemia impairs the in vitro insulin release by islets of Langerhans in response to glucose but exaggerates the in vivo insulin response. We hypothesized that this discrepancy results from increased vagal stimulation of the islets. Conscious chronically cannulated rats were infused with glucose (15 mg/min) or saline for 48 h. Three hours thereafter, an intravenous glucose tolerance test was performed with or without prior injection of atropine (0.2 mg). Atropine markedly (> 70%) reduced the insulin response in glucose-infused, but not in saline-infused, rats. Glucose-infused rats displayed basal hypoglycemia but normal glucose excursions during an intravenous glucose tolerance test. It is concluded that prolonged hyperglycemia produces exaggerated muscarinic activation of the beta-cells that will persist > or = 3 h after the termination of the glucose infusion and normalizes in vivo insulin secretion. It is possible that increased parasympathetic activation of the pancreas might constitute a general mechanism to maintain insulin output when the demand for insulin exceeds the inherent beta-cell responsiveness. PMID- 7864244 TI - Systemic but not central administration of tumor necrosis factor-alpha attenuates LPS-induced fever in rats. AB - The purpose of this study was to test the hypothesis that tumor necrosis factor alpha (TNF) limits fever induced by lipopolysaccharide (LPS) in rats and to determine whether such antipyretic action of this cytokine is outside or inside the central nervous system (CNS). The CNS effects on LPS-induced fever were tested by injecting a subpyrogenic amount (0.20 microgram) of human recombinant TNF (hrTNF) intracerebroventricularly or by slowly infusing into the anterior hypothalamus an amount previously measured in this brain region during LPS fever (0.24 U in 0.13 microliter of artificial cerebrospinal fluid/min). The peripheral effects of this cytokine on LPS fever were tested by injecting 1 micrograms/kg of hrTNF intraperitoneally or by intraperitoneal administration of 300 micrograms/kg of the hrTNF soluble receptor p80 (hrTNFsr). The core temperature (measured by biotelemetry) during LPS fever was not significantly affected by administration of hrTNF intracerebroventricularly or intrahypothalamically. An intraperitoneal injection of hrTNF (1 microgram/kg) had a significant antipyretic effect on febrile response to LPS (mean temperature 2-8 h after injections was 37.28 +/- 0.12 degrees C in rats injected with hrTNF and LPS vs. 38.73 +/- 0.04 degrees C in rats injected with saline and LPS; analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P < 0.05). When rats were injected intraperitoneally with hrTNFsr, the febrile response to LPS was enhanced (analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P < 0.05). These results support the hypothesis that TNF acts to limit the magnitude of LPS-induced fever and that this action occurs outside the CNS. PMID- 7864245 TI - Effects of L-arginine-derived nitric oxide synthesis on neuronal activity in nucleus tractus solitarius. AB - The purpose of these studies was to determine the effects of L-arginine-derived nitric oxide (NO) synthesis on neuronal activity in solitary tract nucleus (NTS) neurons. Single unit activity was recorded extracellularly from medial NTS neurons in Fischer-344 rats in vivo and in vitro. In anesthetized rats with arterial pressure maintained constant, NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv), an inhibitor of NO synthesis, decreased the discharge rate in 12 of 14 neurons and increased the discharge rate in two. After injection of L-NAME, the slowing of neuronal activity began within 2-5 min, and maximal responses were observed 12-15 min after injection. The decreases in activity were reversed within 12-15 min with L-arginine (30 mg/kg iv) or immediately with nitroglycerin (NTG, 10-30 micrograms/kg iv). In superfused rat brain slices, the discharge rate was reduced by 1 mM L-NAME in seven neurons, increased in two, and unchanged in one. The decreases in discharge rate were reversed by 2 mM L-arginine (4 of 6 neurons) and by 10-30 microM NTG (6 of 7 neurons). The results show that L arginine-derived NO can affect the spontaneous discharge rate of NTS neurons. We conclude that NO may influence the excitability of NTS neurons involved in central autonomic control. PMID- 7864246 TI - Neural control of glucose uptake by skeletal muscle after central administration of NMDA. AB - Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow. PMID- 7864247 TI - Moderate, selective depletion of linoleate and alpha-linolenate in weight-cycled rats. AB - In rats, the response of adipose tissue composition to a single weight cycle (24 48 h of fasting followed by refeeding) is characterized by a decrease primarily in linoleate and alpha-linolenate, with little or no change in other fatty acids. We tested the hypothesis that during successive weight cycles caused by repeated fasting and refeeding, the depletion of linoleate and alpha-linolenate from whole body stores would be exacerbated despite their adequate availability during the refeeding period. Four complete weight cycles (24-h fasting followed by 72-h ad libitum refeeding) induced a significant quantitative decrease in total n-3 and n 6 polyunsaturates, particularly linoleate and alpha-linolenate, and a simultaneous increase in the accumulation of palmitate, palmitoleate, and oleate in carcass total lipids and in perirenal and epididymal adipose tissue. A significant positive relationship was observed between the increasing ratio of saturates+monounsaturates to n-3 + n-6 polyunsaturates in adipose tissue and the number of weight cycles (r = +0.96, P < 0.0001). The percentage of linoleate and alpha-linolenate in adipose tissue was inversely related to the number of weight cycles. We conclude that, despite providing adequate n-6 and n-3 polyunsaturates in the diet during the refeeding period, weight cycling in young growing rats causes a moderate, selective depletion of linoleate and alpha-linolenate from tissue stores. PMID- 7864248 TI - Intracellular Ca2+ transients evoked by lactic acid in cultured mammalian neurons. AB - During cerebral ischemia, accumulation of the glycolytic end product lactic acid may contribute to brain infarction. In vitro, lactic acid evokes a process of slowly evolving neuronal death characterized by a transient maintenance of cellular viability after initial injury. We examined effects of lactic acid on intracellular Ca2+ (Cai2+). Cultured neurons loaded with the fluorescent Ca2+ indicator fura 2 showed a marked increase in Cai2+ to as high as 600 nM. This increase occurred after lactic acid exposure when intracellular pH had normalized. Membrane potential was unaltered during this period, indicating that the Cai2+ increment was not a result of membrane depolarization. Increase in Ca2+ was prevented by incubating cultures in Ca(2+)-free solutions or exposing them to the L-type Ca2+ channel antagonist nimodipine. Cai2+ returned to resting levels within 20 min and remained normal during the remainder of the 4-h observation period. Neuronal Ca2+ homeostasis was disrupted after lethal exposure to lactic acid, in that subsequent exposure to 50 mM K+ failed to increase neuronal Cai2+. Cai2+ increment was integrated over a 20-min period to obtain a measure of neuronal Cai2+ load. This "calcium integral" was found to correlate directly with severity of neuronal damage observed 24 h later. Thus the Cai2+ increase integrated over time closely reflected the likelihood of lethal neuronal injury after lactic acid exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864249 TI - Endotoxin tolerance alters thermal response of guinea pigs to systemic infusions of tumor necrosis factor-alpha. AB - In guinea pigs, intra-arterial infusions of 5 micrograms/kg tumor necrosis factor alpha (TNF; specific activity 20,000 U/micrograms; duration of infusion 45-50 min) evoked a biphasic elevation of abdominal temperature lasting approximately 6 h. One week after systemic infusion of TNF, the animals started to receive either five intramuscular injections of bacterial lipopolysaccharide (LPS from Escherichia coli; 20 micrograms/kg) or equivalent volumes of solvent (0.9% NaCl) in intervals of 3 days. Fever in response to repeated injections of LPS was progressively attenuated; the animals developed endotoxin tolerance. Repeated injections with solvent did not cause any measurable changes in abdominal temperature. Three days after the fifth injection of LPS or solvent, all animals again received an intra-arterial infusion of 5 micrograms/kg TNF. In guinea pigs injected five times with solvent, the biphasic elevation of abdominal temperature could again be observed in response to systemic infusions of TNF. In endotoxin tolerant animals, however, only the first peak of the biphasic thermal response lasting approximately 60 min could be monitored after infusions with TNF. The second phase of the thermal response to administration of TNF, which normally lasts > 5 h, was abrogated almost completely. The significant suppression of the febrile response to TNF infusions did not seem to be caused by a more rapid elimination of TNF from the circulation of endotoxin-tolerant guinea pigs. Circulating levels of TNF, measured 60 and 180 min after the start of TNF infusions, were not different before and after development of endotoxin tolerance. In conclusion, the development of endotoxin tolerance in guinea pigs is accompanied by a reduced responsiveness to TNF administered exogenously. PMID- 7864250 TI - Diet-independent suppression of ingestive behavior by cholecystokinin octapeptide and amino acids. AB - Male rats consumed much more of an intraorally administered mixed protein, fat and carbohydrate solution than of a carbohydrate solution. Injection of cholecystokinin octapeptide (CCK-8, 0.6-5.0 microgram) suppressed intake of both solutions, but the CCK-A receptor antagonist L-364, 718 (20-40 micrograms) facilitated only carbohydrate intake. Blood levels of CCK-8 were higher after intake of the carbohydrate than the mixed solution. Blood levels of isoleucine, leucine, lysine, threonine, valine, and tryptophan increased only after intake of the mixed solution. Injection of these amino acids suppressed intake of both solutions. Blood levels of amino acids were also less after the seventh than after the first session ingesting the mixed solution. Treatment with CCK-8 or amino acids inhibits intake of any diet, but when secreted endogenously, these signals may terminate the meal in a diet-dependent manner. PMID- 7864251 TI - Differential effects of bright light and social cues on reentrainment of human circadian rhythms. AB - Reentrainment of human circadian rhythm to an 8-h advanced schedule of sleep and social contacts was assessed under two different conditions: with and without bright light (4,000-6,000 lx). Subjects spent 15 days without knowing the natural day-night alternation. On the fourth day, the social schedule was phase-advanced by 8 h. In one experiment, a bright light pulse of 3-h duration was given in every subjective morning, and in the other no light pulse was applied. Plasma melatonin and rectal temperature rhythms were measured. Seven of nine subjects showed an orthodromic phase shift, the rate of which was significantly larger with bright light pulses than without them. The maximum phase-advance shift by three consecutive light pulses was observed when the first pulse was applied approximately 4 h after the onset of melatonin rise. By contrast, the maximum phase shift of a similar extent was detected at 1 h after the onset of melatonin rise, when ordinary room light (300-500 lx) at the time corresponding to bright light was regarded as a dim light pulse. It is concluded that bright light accelerates the reentrainment of human circadian rhythm, and bright light and social schedule have differential effects on the reentrainment. PMID- 7864252 TI - Rates of local cerebral protein synthesis in the rat during normal postnatal development. AB - The degree of recycling of leucine derived from protein breakdown into the precursor pool for protein synthesis was measured in rat brain at different postnatal ages, and age-specific values were used in the calculation of regional (local) rates of cerebral leucine incorporation into protein (lCPSleu) in 44 brain regions and the brain as a whole. Early in development, a greater fraction of the precursor leucine pool is derived from protein breakdown, indicating that protein degradation is higher in young rats compared with adults. In whole brain and in most regions, values for lCPSleu were highest at 10 days and gradually decreased with age. By 60 days of age, values in cortex were approximately 60% of those at 10 days of age. In the paraventricular and supraoptic nuclei of the hypothalamus, however, lCPSleu increased during development, reaching peak values in adults. In white matter of the cerebellum and the cerebrum, peaks of lCPSleu were reached at 14 and 21 days, respectively, approximately at the times of maximum rates of myelination. PMID- 7864253 TI - Additive effects of obesity and hypertension to limit venous volume. AB - The presence of reduced venous distensibility in obesity might have important hemodynamic effects and could indirectly implicate a role for metabolic factors in vascular control, because loading conditions are different in arterial and in venous vessels. Forearm blood flow and venous volume were measured plethysmographically in 58 subjects, including lean and obese hypertensives and normotensives. Venous volume at 30 mmHg (VV30) was decreased by both obesity and hypertension. This coincided with evidence for better preservation of central blood and stroke volumes with upright posture in obese than in lean subjects. Furthermore, obese hypertensives had lower VV30 than either lean hypertensives or obese normotensives. Postischemic forearm vascular resistance, a surrogate marker for structural luminal cross-sectional area, percent body fat, and fasting insulin each correlated independently with VV30 (P < 0.05) in multivariate analysis. Because nonesterified fatty acid levels are elevated in obese hypertensives and may have potent vascular effects, dorsal hand vein responses to coinfusion of Intralipid 10% and heparin to raise fatty acids locally were obtained in normal volunteers. The local infusion of Intralipid with heparin reduced hand vein distensibility, whereas dextrose and heparin did not (11 +/- 3% vs. 0 +/- 2%, respectively, P < 0.01). This study indicates that obesity and mild hypertension each reduce venous distensibility and that the coexistence of both conditions produces an even greater impairment in venous capacitance. The reduced venous distensibility in obesity appears to reflect structural as well as functional factors and to have systemic hemodynamic effects. PMID- 7864254 TI - H2 gas clearance technique for separating rat uterine blood flow into endometrial and myometrial components. AB - The H2 gas clearance technique was employed to measure uterine blood flow (UBF) in ovariectomized rats. A needle-type platinum electrode (125 microns diam) was inserted into the rat uterine wall to measure the tissue blood flow surrounding the electrode. The electrode can be placed in individual layers of the uterus to measure the endometrial blood flow (EBF) or the myometrial blood flow (MBF). By use of this technique, baseline EBF and MBF were 37.8 +/- 3.53 (n = 21) and 47.2 +/- 4.56 (n = 5) ml.min-1.100 g-1, respectively, with an EBF/MBF ratio of 0.8. Intravenous bolus injection of 17 beta-estradiol (1 microgram/kg) induced a significant increase in UBF. Phenylephrine, an alpha-adrenergic receptor agonist, reduced UBF. In some animals, a second platinum electrode was used to measure gastric mucosal blood flow simultaneously with UBF. While 17 beta-estradiol selectively increased UBF, pentagastrin selectively increased gastric mucosal blood flow. To further validate the baseline UBF distribution between endometrial and myometrial layers, iodo[14C]antipyrine autoradiography was employed. With the iodo[14C]antipyrine technique, the EBF/MBF ratio was 0.91 +/- 0.07 (n = 5), which is similar to that obtained with the H2 gas clearance technique. PMID- 7864255 TI - Mapping brain activity associated with emotion. PMID- 7864256 TI - Images in neuroscience. Cortex, V. Prefrontal leukotomy. PMID- 7864257 TI - The glutamatergic basis of human alcoholism. AB - OBJECTIVE: Although alcoholism is one of the most common psychiatric diagnoses, understanding of its pathophysiology remains poor. Accumulating evidence suggests that neurophysiological and pathological effects of ethanol are mediated to a considerable extent through the glutamatergic system. This article reviews the evidence of ethanol's effects on glutamatergic transmission and proposes a glutamatergic basis for alcoholism. METHOD: The information was derived from original research. The authors located more than 100 articles from psychiatry and neuroscience journals that related ethanol to glutamatergic transmission. They critically reviewed the neurobiology of the glutamatergic system in alcoholism and synthesized a unifying glutamatergic theory. RESULTS: Acute effects of ethanol disrupt glutamatergic neurotransmission by inhibiting the response of the N-methyl-D-aspartate (NMDA) receptor. Prolonged inhibition of the NMDA receptor by ethanol results in development of supersensitivity; acute removal of ethanol causes marked augmentation of activity of postsynaptic neurons, such as those in the noradrenergic system, and, in the extreme, glutamate-induced excitotoxicity. Neurobiological effects of alcoholism, such as intoxication, withdrawal seizures, delirium tremens, Wernicke-Korsakoff syndrome, and fetal alcohol syndrome, can be understood as a spectrum of consequences of ethanol's effect on the glutamatergic system. CONCLUSIONS: A host of findings support the hypothesis that the unifying mechanism of action of ethanol in interference with glutamatergic neurotransmission, especially through the NMDA receptor. Alcoholism may be considered another member of the expanding family of glutamate-related neuropsychiatric disorders. These insights should increase understanding of the biologic vulnerabilities leading to ethanol abuse and dependence and aid development of more effective pharmacologic interventions. PMID- 7864258 TI - Brain activity during transient sadness and happiness in healthy women. AB - OBJECTIVE: The specific brain regions involved in the normal emotional states of transient sadness or happiness are poorly understood. The authors therefore sought to determine if H2(15)O positron emission tomography (PET) might demonstrate changes in regional cerebral blood flow (rCBF) associated with transient sadness or happiness in healthy adult women. METHOD: Eleven healthy and never mentally ill adult women were scanned, by using PET and H2(15)O, during happy, sad, and neutral states induced by recalling affect-appropriate life events and looking at happy, sad, or neutral human faces. RESULTS: Compared to the neutral condition, transient sadness significantly activated bilateral limbic and paralimbic structures (cingulate, medial prefrontal, and mesial temporal cortex), as well as brainstem, thalamus, and caudate/putamen. In contrast, transient happiness had no areas of significantly increased activity but was associated with significant and widespread reductions in cortical rCBF, especially in the right prefrontal and bilateral temporal-parietal regions. CONCLUSIONS: Transient sadness and happiness in healthy volunteer women are accompanied by significant changes in regional brain activity in the limbic system, as well as other brain regions. Transient sadness and happiness affect different brain regions in divergent directions and are not merely opposite activity in identical brain regions. These findings have implications for understanding the neural substrates of both normal and pathological emotion. PMID- 7864259 TI - Health care costs associated with depressive and anxiety disorders in primary care. AB - OBJECTIVE: The authors examined the overall health care costs associated with depression and anxiety among primary care patients. METHOD: Of 2,110 consecutive primary care patients in a health maintenance organization, 1,962 were screened with the 12-item General Health Questionnaire. A stratified random sample of 615 patients were selected for further diagnostic assessment; 373 of these patients completed the Composite International Diagnostic Interview at baseline and 328 were reassessed 12 months later. Computerized cost records were used to calculate total health care costs for the 6-month period surrounding the baseline assessment and a similar period surrounding the follow-up assessment. Cost accounting data were available for 327 patients at baseline and for 206 patients at both assessments. RESULTS: Primary care patients with DSM-III-R anxiety or depressive disorders at baseline had markedly higher baseline costs ($2,390) than patients with subthreshold disorders ($1,098) and those with no anxiety or depressive disorder ($1,397). Large cost differences persisted after adjustment for medical morbidity. Cost differences reflected higher utilization of general medical services rather than higher mental health treatment costs. Although most patients with baseline anxiety or depressive disorders showed significant improvement, longitudinal analyses did not show any clear relationship between change in psychiatric diagnosis and change in health care cost. CONCLUSIONS: Among primary care patients, anxiety and depressive disorders are associated with markedly higher health care costs even after adjustment for medical comorbidity. In this small sample, improvement in depression over 1 year was not clearly associated with decreases in cost. PMID- 7864260 TI - Disproportionate suicidality in patients with comorbid major depression and alcoholism. AB - OBJECTIVE: The two purposes of this study were to provide a comprehensive description of the clinical features of patients who presented to an intake psychiatric setting with major depression and alcohol dependence and to determine which clinical features distinguished this dual-diagnosis group from patients with the two relevant single diagnoses. METHOD: During a recent 5-year period, a total of 107 patients who came to a psychiatric facility for initial evaluation were diagnosed as having both major depression and alcohol dependence. The clinical profile of this dual-diagnosis group was compared to that of nondepressed alcoholics (N = 497) and nonalcoholic patients with major depression (N = 5,625), assessed at the same facility, on the basis of information from the Initial Evaluation Form, a semistructured instrument containing a standardized symptom inventory that includes ratings of severity. RESULTS: The psychiatric symptom that most strongly distinguished the depressed alcoholics from the two comparison groups was the level of suicidality. The depressed alcoholics differed significantly from the nonalcoholic depressed patients on only two depressive symptoms, suicidality (59% higher) and low self-esteem (22% higher); they were also significantly distinguished from the nonalcoholic depressed patients by factors such as greater impulsivity, functional impairment, and abnormal personal and social history markers. CONCLUSIONS: Suicidality was disproportionately greater than other psychiatric symptoms in the depressed alcoholics. The clinical profile of depressed alcoholics suggests that they suffer an additive or synergistic effect of two separate disorders, resulting in a disproportionately high level of acute suicidality upon initial psychiatric evaluation. PMID- 7864261 TI - Alcoholism in manic-depressive (bipolar) illness: familial illness, course of illness, and the primary-secondary distinction. AB - OBJECTIVE: This 5-year follow-up study was designed to explore the factors that might lead to alcoholism in patients with bipolar disorder. METHOD: The authors studied patients with bipolar illness (70 with alcoholism and 161 without), their relatives, and a comparison group composed of relatives' acquaintances. All were evaluated with versions of the Schedule for Affective Disorders and Schizophrenia, and diagnoses were made according to the Research Diagnostic Criteria. Thirty of the bipolar alcoholic patients whose affective disorder was primary were also compared with 34 whose alcoholism was primary. RESULTS: Alcoholism was more frequent in the bipolar patients than in the comparison subjects. There no significant differences between the alcoholic and nonalcoholic bipolar patients in family history of alcoholism or affective disorders, suggesting that bipolar illness with alcoholism is not explicable by a family history of alcoholism and that the alcoholism seen in bipolar illness is dissimilar to alcoholism as a primary disorder. Alcoholism associated with bipolar illness was more likely to remit than primary alcoholism. There was no significant difference in family history between the patients with primary alcoholism and those with primary bipolar disorder. The patients with primary alcoholism had significantly fewer episodes of affective disorder during followup, suggesting that their type of bipolar illness was less severe and may have needed the added insult of alcoholism to make it manifest. CONCLUSIONS: The study supports the idea that not all alcoholism is primary with a corresponding familial diathesis. Rather, alcoholism associated with bipolar disorder is often a secondary complication. PMID- 7864262 TI - Major depression in a community sample of African Americans. AB - OBJECTIVE: This study examined demographic, sociocultural, familial background, and health-related risk factors for major depression in a community sample of African Americans. METHOD: Data came from a probability sample of 865 urban African American adults, 20 years of age and older, who were given the structured National Institute of Mental Health Diagnostic Interview Schedule. RESULTS: The findings indicated a 1-year prevalence of 3.1% for major depression. While age, residential mobility, health status, and stressful life events were significantly associated with major depression, none of the sociocultural and family background factors were. The strongest predictors of major depression were poor or fair health and being 20-29 years of age. In terms of treatment for depression, persons with major depression were significantly more likely than those without to engage in help seeking. However, only 11.1% actually saw a psychiatrist or other mental health professional, and 7.4% saw no one. CONCLUSIONS: Young age and fair to poor physical health appear to be more powerful risk factors for major depression among African Americans than other demographic, sociocultural, and family background variables. Few African Americans with major depression actually receive clinical treatment for this illness. The results further suggest the need to increase awareness of major depression among general practitioners and to target outreach to African American communities. PMID- 7864263 TI - Course and outcome in bipolar affective disorder: a longitudinal follow-up study. AB - OBJECTIVE: A number of recent studies have questioned whether, despite modern treatment, the natural course of bipolar illness today still involves multiple relapses and impaired psychosocial functioning. This prospective follow-up study examined longitudinal outcome in a large group of inpatients with affective disorders. METHOD: Fifty-one bipolar manic patients and 49 unipolar depressed patients were interviewed three times: 1) during hospitalization, 2) approximately 2 years after discharge, and 3) approximately 4.5 years after discharge. Subjects were treated under routine conditions and assessed for global adjustment, rehospitalization, and work and social functioning. RESULTS: Only 41% of the bipolar group had a good overall outcome by the time of the 4.5-year follow-up. The bipolar patients had more severe work impairment than the unipolar group. More than one-half of the bipolar patients were rehospitalized at least once during the 4.5-year follow-up period. Outcome for both diagnostic groups improved significantly over time. CONCLUSIONS: Many contemporary bipolar patients demonstrate gradual improvement in the first several years after hospitalization. However, a subgroup approaching 60% still experience poor posthospital adjustment in one or more areas of functioning. PMID- 7864264 TI - Long-term stability of polarity distinctions in the affective disorders. AB - OBJECTIVE: This analysis aimed to quantify the long-term stability of distinctions between nonbipolar, bipolar II, and bipolar I affective disorders and to determine the predictors of shifts in patients' diagnoses among these categories. METHOD: Probands entered the study as they sought treatment for manic, major depressive, or schizoaffective disorder diagnosed according to the Research Diagnostic Criteria. After thorough baseline evaluations, 605 patients with nonbipolar major depressive disorder or schizoaffective disorder, depressed type; 96 with bipolar II disorder; and 231 with bipolar I disorder or schizoaffective disorder, manic type, began the follow-up study. Direct interviews took place at 6-month intervals for the first 5 years and annually thereafter. RESULTS: Only 20 (5.2%) of the 381 initially nonbipolar probands who completed 10 years of follow-up developed mania during that time, and only 19 (5.0%) developed hypomania. A slightly higher proportion of the 67 who began with bipolar II disorder developed mania during the 10 years. Although 101 (66.4%) of the 152 bipolar I or schizoaffective manic probands developed subsequent manic episodes, only 11 (7.2%) developed hypomanic episodes and no mania. Young age at intake and at onset and chronicity of the index episode predicted shifts from nonbipolar to bipolar II disorder. Psychosis and a family history of mania predicted shifts from nonbipolar to bipolar I disorder. CONCLUSIONS: The high stability of baseline distinctions between nonbipolar, bipolar II, and bipolar I disorders, in combination with previously described family study data, strongly supports the separation of these disorders for both clinical and research purposes. PMID- 7864265 TI - Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics. AB - OBJECTIVE: The authors tested the hypothesis that fluoxetine, when used in combination with relapse prevention psychotherapy, directly reduces relapse frequency and severity for alcoholics. METHOD: The authors conducted a randomized, placebo-controlled trial of fluoxetine (up to a maximum of 60 mg/day) for 12 weeks in combination with weekly psychotherapy for 101 alcohol-dependent subjects who were not selected on the basis of comorbid major depression. Outcomes were measured at the end of treatment and 6 months after treatment. RESULTS: Placebo-treated subjects were more complaint with the medication regimen and remained in the study longer than fluoxetine-treated subjects. There was significantly less alcohol consumption in both groups during treatment than before treatment. These effects persisted during the posttreatment period. Although fluoxetine treatment had no significant effects on alcohol consumption, it reduced Hamilton Depression Rating Scale scores more than placebo treatment among subjects with current major depression. CONCLUSIONS: Fluoxetine at a dose of 60 mg/day is probably not of use for relapse prevention in alcoholics with mild to moderate alcohol dependence and no comorbid depression. In alcoholics with major depression, the drug may reduce depressive symptoms. Subsequent studies with fluoxetine should probably focus on more severely alcohol-dependent subjects or those with comorbid depression. PMID- 7864266 TI - Mood, major depression, and fluoxetine response in cigarette smokers. AB - OBJECTIVE: Two smoking cessation studies provided venues to 1) look for differences in affective symptoms between cigarette smokers with and without a history of major depression or other psychiatric diagnoses who were not currently depressed and 2) evaluate the efficacy of fluoxetine in ameliorating affective symptoms in smokers with a history of major depression but not currently depressed. METHOD: Part I: Three hundred sixty-eight smokers who enrolled in a smoking cessation treatment study completed baseline self-rating scales. The relationship between the scale scores and a history of major depression and other psychiatric diagnoses was examined. Part II: Thirty-nine smokers with a history of major depression were enrolled in a randomized, double-blind study that examined the utility of fluoxetine as an aid to smoking cessation. Self-rated scales were compared at baseline and after 3 weeks of medication treatment before the attempt to quit. RESULTS: A history of major depression had significant main effects across all scale scores; subjects with such a history rated themselves as more symptomatic. The effects of other psychiatric diagnoses were neither as pervasive nor as robust. There were no differences in baseline scores between the fluoxetine- and placebo-treated groups and no change within the placebo group after 3 weeks. There was significant improvement from baseline in several subscale scores for the group treated with fluoxetine. However, comparison of the score changes for the placebo and fluoxetine groups did not show a statistically significant difference, which limited the ability to conclude that active treatment was better than placebo. CONCLUSIONS: Subjects with a history of major depression, but without current affective illness, reported themselves to be more symptomatic than those without such-a history. Furthermore, in a group of smokers with a history of major depression, affective symptoms, without concurrent syndromal illness, may be ameliorated by treatment with fluoxetine. PMID- 7864267 TI - Early versus late partial sleep deprivation in patients with premenstrual dysphoric disorder and normal comparison subjects. AB - OBJECTIVE: The aim of this study was to compare the clinical effects of early night and late-night partial sleep deprivation in patients with premenstrual dysphoric disorder and normal comparison subjects. METHOD: In the premenstrual phase of two menstrual cycles, 23 subjects with DSM-IV premenstrual dysphoric disorder and 18 normal comparison subjects underwent a randomized crossover trial of 1) early-night sleep deprivation, in which subjects slept from 3:00 a.m. to 7:00 a.m., followed by a night of recovery sleep (11:00 p.m. to 7:00 a.m.), and 2) late-night sleep deprivation, in which subjects slept from 9:00 p.m. to 1:00 a.m., followed by a night of recovery sleep. RESULTS: For the subjects with premenstrual dysphoric disorder, in both partial sleep deprivation conditions the Hamilton and Beck depression ratings were significantly lower after recovery sleep than at baseline. Ratings on the day after early or late partial sleep deprivation tended to be lower than at baseline but were not statistically different. The normal comparison subjects showed no clinically important mood changes. A factor analytic approach used with the Hamilton depression scores showed that depressive retardation symptoms were the most responsive to sleep deprivation in the premenstrual dysphoric disorder subjects. CONCLUSIONS: These results are consistent with the reported efficacy of sleep deprivation for major depressive disorder. However, the premenstrual dysphoric disorder subjects improved after the recovery sleep rather than directly after partial sleep deprivation. That late-night sleep deprivation did not have greater benefit than did the hypothesized sham treatment, early-night sleep deprivation, also suggests that placebo effects cannot be ruled out. PMID- 7864268 TI - Blood dyscrasias with carbamazepine and valproate: a pharmacoepidemiological study of 2,228 patients at risk. AB - OBJECTIVE: The purpose of this study was to determine the occurrence of leukopenia and other blood dyscrasias associated with psychiatric use of carbamazepine and valproate. METHOD: Rates of WBC counts of 3,000-4,000/mm3 (moderate leukopenia) and < 3,000/mm3 (severe leukopenia), platelet counts of < 100,000/mm3, and hematocrit < 30% were identified among 2,228 treated patients at risk among 11,720 patients admitted to McLean Hospital over 4 years (1989-1993). Patients who received carbamazepine or valproate and had a blood dyscrasia not associated with a relevant medical condition were compared to patients treated with imipramine or desipramine. RESULTS: Of 977 patients treated with carbamazepine, 2.1% experienced leukopenia (16 moderate cases, five severe). Time to 50% risk was 16 days, and recovery occurred within about 6 days after carbamazepine was stopped. For 1,251 patients given valproate, the occurrence of leukopenia was 0.4% (three moderate cases, two severe). The occurrence of leukopenia in 1,031 patients given the tricyclic antidepressants was 0.3% (two moderate cases, one severe). The observed occurrence of moderate leukopenia with carbamazepine was 6.9 and 7.3 times higher than that with valproate and antidepressants, respectively. CONCLUSIONS: Severe blood dyscrasias were uncommon in psychiatric patients given carbamazepine and were about as rare with valproate as with imipramine or desipramine. Most important, in this cohort of 2,228 patients exposed to carbamazepine and valproate, there were no life-threatening cases. PMID- 7864269 TI - Low serum cholesterol level and attempted suicide. AB - OBJECTIVE: Several studies suggest that a low cholesterol concentration is associated with a greater than normal risk of mortality from suicide. The authors sought to determine whether a low cholesterol level is associated with a history of serious suicide attempts among psychiatric inpatients. METHOD: Lifetime history of attempted suicide of 650 patients, aged 18-59 years, consecutively admitted to a psychiatric hospital was assessed by semistructured interview. The seriousness of an attempt was rated on the basis of the resulting medical injury. Serum cholesterol levels, obtained from the admission biochemical profiles, were divided into quartiles. RESULTS: Compared to men with low cholesterol levels (defined as less than or equal to the 25th percentile), men with cholesterol levels above the 25th percentile were less likely to have ever made a serious suicide attempt when age, weight, race, socioeconomic status, alcohol use, and depression were controlled for. There was no association between cholesterol level and attempted suicide in women. CONCLUSIONS: Male psychiatric patients with low cholesterol levels were twice as likely to have ever made a medically serious suicide attempt than men with cholesterol levels above the 25th percentile. Low cholesterol concentration should be further investigated as a potential biological marker of suicide risk. PMID- 7864270 TI - Age at onset and familial risk in Alzheimer's disease. AB - OBJECTIVE: The authors investigated the relationship between probands' age at onset of Alzheimer's disease with the risk of primary progressive dementia in the probands' first-degree relatives. METHOD: Two hundred probands with clinically diagnosed Alzheimer's disease and 179 nondemented elderly probands were recruited from the Mount Sinai Alzheimer's Disease Research Center, located at Mount Sinai Hospital and the Bronx Veterans Affairs Medical Center. Demographic and diagnostic data were collected on 1,398 of the first-degree relatives of the probands with Alzheimer's disease and 955 first-degree relatives of the nondemented probands. RESULTS: Cox proportional hazards regression analysis showed a significant inverse relationship between age at onset of Alzheimer's disease in probands and greater familial risk in their relatives. Follow-up analyses indicated that the most commonly used age at onset cutoff point--65 years--was one of the points where an association with familial aggregation is least likely to be revealed; other onset cutoff ages (e.g., 55, 70, and 75) better identified Alzheimer's disease groups with differing familial/genetic risks. CONCLUSIONS: The authors conclude that patients with an earlier age at onset of Alzheimer's disease are more likely to have relatives with Alzheimer's disease than are patients with a later age at onset of the disease. An onset age of 70 best differentiated probands whose relatives were at higher risk from those whose relatives were at lower risk. PMID- 7864271 TI - High risk for attention deficit hyperactivity disorder among children of parents with childhood onset of the disorder: a pilot study. AB - OBJECTIVE: Although well-documented in clinical and epidemiological studies of attention deficit hyperactivity disorder (ADHD) in children, the familial nature of the adult syndrome has not been well investigated. One approach to evaluate the familial nature of adult ADHD is through a high-risk design aimed at estimating the risk for the disorder in children of parents with child-hood-onset ADHD. METHOD: Children at risk for ADHD were ascertained from the study group of 84 referred adults with clinical diagnoses of childhood onset of the disorder, confirmed by structured interviews. Diagnostic information on the disorder was derived from the ADHD module of the Schedule for Affective Disorders and Schizophrenia for School Age Children--Epidemiologic Version, supplemented with information regarding treatment for ADHD for the affected child and school history including repeated grades, placement in special classes, and tutoring. RESULTS: Of the 84 children at risk, 48 (57%) met criteria for ADHD. The rate of the disorder in children of adults with the disorder was significantly higher than the previously reported rate of ADHD among siblings of children with the disorder. Of the 48 ADHD children of parents with the disorder, 36 (75%) were treated for it. The rates of school failure were almost identical to those previously reported in a group of referred children and adolescents with ADHD. CONCLUSIONS: These results support the validity of the adult diagnosis of ADHD and suggest that the adult form of this disorder may have stronger familial etiological risk factors than its pediatric form. If these results are confirmed, families selected through adult probands with ADHD might be especially useful for testing genetic hypotheses about the disorder. PMID- 7864272 TI - Exclusion of the 5-HT1A serotonin neuroreceptor and tryptophan oxygenase genes in a large British kindred multiply affected with Tourette's syndrome, chronic motor tics, and obsessive-compulsive behavior. AB - OBJECTIVE: Previous studies have demonstrated a relationship between obsessive compulsive disorder or behavior and Gilles de la Tourette syndrome. It has been hypothesized that the serotonergic system is implicated in the etiology of obsessive-compulsive disorder. Therefore, the authors investigated whether genetic variation in a serotonergic receptor and a modifying enzyme were associated with Tourette's syndrome. METHOD: A linkage analysis using DNA and blood group markers was carried out in a large British kindred multiply affected with Tourette's syndrome, chronic motor tics, and obsessive-compulsive behavior. RESULTS: There was no evidence to support the hypothesis that genetic variation in the serotonin 5-HT1A receptor and tryptophan oxygenase genes causes susceptibility to Tourette's syndrome and chronic multiple tics. CONCLUSIONS: The results eliminate two possible candidate genes from having a role in the pathophysiology of Tourette's syndrome. PMID- 7864273 TI - Family accommodation in obsessive-compulsive disorder. AB - OBJECTIVE: Family accommodation of patients with obsessive-compulsive disorder, i.e., participation in symptoms and modification of personal and family routines, was assessed in relation to family stress, functioning, and attitudes toward the patient. METHOD: Primary caretakers for 34 patients with obsessive-compulsive disorder were interviewed to assess the nature and frequency of accommodating behaviors. The caretakers also completed several measures of family functioning. RESULTS: Of the 34 spouses or parents, 30 (88.2%) reported accommodating the patient. Family accommodation correlated with poor family functioning, rejecting attitudes toward the patient, and several types of family stress. CONCLUSIONS: Family accommodation of patients with obsessive-compulsive disorder was associated with global family dysfunction and stress. This study suggests that families' efforts to accommodate patients may be intended to reduce patient anxiety or anger directed at relatives. PMID- 7864274 TI - Temporal lobe proton magnetic resonance spectroscopy of patients with first episode psychosis. AB - OBJECTIVE: The authors measured the ratio of N-acetyl aspartate (a putative neuronal marker) to creatine-phosphocreatine in patients with first-episode psychosis by using proton magnetic resonance spectroscopy (MRS). METHOD: Temporal lobe 1H MRS was performed bilaterally on 13 patients with first-episode psychosis and 15 comparison subjects. The N-acetyl aspartate/creatine-phosphocreatine and choline/creatine-phosphocreatine ratios were determined. RESULTS: The N-acetyl aspartate/creatine-phosphocreatine ratio of the psychotic patients was significantly lower than that of the comparison subjects. CONCLUSIONS: These preliminary data suggest that abnormalities in temporal lobe N-acetyl aspartate concentration are present early in psychotic illness. PMID- 7864275 TI - Quantitative magnetic resonance imaging of the brain in late-life schizophrenia. AB - OBJECTIVE: This study compared morphometric analyses of brain regions in elderly subjects with early- or late-onset schizophrenia to identify structural abnormalities responsible for schizophrenia. METHOD: Quantitative analyses of magnetic resonance images of the brain were performed in 16 patients with DSM-III R-diagnosed late-onset schizophrenia (i.e., onset after age 45), 14 patients with early-onset schizophrenia, and 28 normal comparison subjects, all of whom were over the age of 45. The three groups were similar in age, sex, education, and handedness. RESULTS: The groups differed significantly in ventricular and thalamic volumes. The patients with late-onset schizophrenia had significantly larger ventricles than the normal comparison subjects and significantly larger thalamic volumes than the patients with early-onset schizophrenia. There were no significant linear correlations between thalamic volume and age at onset, duration of illness, or mean current neuroleptic dose. CONCLUSIONS: Differences in thalamic volume may account for the putative disruption in thalamofrontal ciruitry in schizophrenia. PMID- 7864276 TI - Schizophrenia following in utero exposure to the 1957 influenza epidemics in Japan. AB - OBJECTIVE: Studies in Finland, England, and Denmark have reported that individuals exposed to the 1957 A2 influenza pandemic during their second trimester in utero are at greater risk for later schizophrenia. However, other studies in England, the United States, and Holland reported no such association. The authors' goal was to shed light on these conflicts. METHOD: They compared the number of individuals who later developed schizophrenia who were born in the 5 months after the peak prevalence of three distinct 1957 influenza epidemics in Japan with the mean number of individuals who later developed schizophrenia who were born in the corresponding months of the 4 years surrounding the epidemics. RESULTS: A significantly greater number of females but not males who later developed schizophrenia were born during the risk exposure months than in the non risk-exposure months. CONCLUSIONS: These findings, although weak, lend support to the claim that in utero exposure to influenza epidemics is a risk factor for adult schizophrenia. PMID- 7864277 TI - Schizophrenia and smoking: an epidemiological survey in a state hospital. AB - OBJECTIVE: The authors sought to determine whether smoking is related to schizophrenia or neuroleptic treatment. METHOD: Cigarette smoking was measured in all patients hospitalized at a state hospital (N = 360) and compared in relation to gender and diagnosis (schizophrenic versus nonschizophrenic). RESULTS: The overall frequency of smoking was 79% (N = 284). Male schizophrenic patients had the highest frequency of smoking, followed by male nonschizophrenic patients, female schizophrenic patients, and female nonschizophrenic patients, respectively. Schizophrenia and polydipsia were associated with both smoking and heavy smoking. CONCLUSIONS: After correction for other variables, schizophrenia appears to increase the risk of being both a smoker and a heavy smoker. There was a possible association between high doses of neuroleptics and smoking but only for nonschizophrenic patients. PMID- 7864278 TI - Substance abuse and family relationships of persons with severe mental illness. AB - OBJECTIVE: The authors sought to determine how substance abuse affects family relationships of persons with severe mental illness. METHOD: Patient reports of family relationships were compared between 101 psychiatric inpatients with a concurrent substance use disorder and 78 subjects with severe mental illness only. RESULTS: Patients with comorbid substance abuse reported significantly lower family satisfaction and a greater desire for family treatment. Objective indicators of frequency of family contact did not differ. CONCLUSIONS: Substance abuse is associated with low levels of satisfaction with family relationships among persons with severe mental illness. Family interventions would meet the stated needs of persons with mental illness and a comorbid substance use disorder and might help to engage them in treatment. PMID- 7864279 TI - Adjustment disorder as an admission diagnosis. AB - OBJECTIVE: The authors' goal was to study subtyping, demographic variables, suicidality, diagnostic stability, and 2-year rehospitalization outcome for inpatients given the admission diagnosis of adjustment disorder at their institution. METHOD: They reviewed the charts of 54 adolescent and 102 adult inpatients given the diagnosis of adjustment disorder at admission and compared them with the charts of 156 matched comparison subjects given other admission diagnoses. RESULTS: Adolescents and adults with adjustment disorder had significantly shorter index hospitalizations and more presenting suicidality than the comparison subjects. Adults but not adolescents with adjustment disorder had significantly fewer psychiatric readmissions and fewer rehospitalization days 2 years after discharge than comparison subjects, and more adults with adjustment disorder had diagnoses of comorbid substance use disorder. Forty percent of the patients admitted with the diagnosis of adjustment disorder were discharged with different diagnoses. Only 18% of the inpatients with adjustment disorder who were rehospitalized were given that diagnosis at readmission. CONCLUSIONS: Adjustment disorder diagnoses were associated with suicidality, shorter lengths of stay, and, in adults, more substance use disorders and fewer rehospitalizations. PMID- 7864280 TI - Fibrocystic breast disease following treatment with selective serotonin reuptake inhibitors. PMID- 7864281 TI - Posttraumatic stress disorder with psychotic features. PMID- 7864282 TI - Management of clozapine-induced enuresis. PMID- 7864283 TI - Midazolam for treatment of agitation after ECT. PMID- 7864284 TI - Effects of fluoxetine on serum clozapine levels. PMID- 7864285 TI - Association between cognitive deficits and temporal lobe abnormalities. PMID- 7864286 TI - Association between cognitive deficits and temporal lobe abnormalities. PMID- 7864287 TI - First-episode schizophrenia and depression. PMID- 7864288 TI - Mother-child interaction and borderline personality disorder. PMID- 7864289 TI - Sexual harassment. PMID- 7864290 TI - Sexual harassment. PMID- 7864291 TI - Sexual harassment. PMID- 7864292 TI - Genetics of personality disorder. PMID- 7864293 TI - Gender differences in income for psychiatrists. PMID- 7864294 TI - Reticulohistiocytoma and multicentric reticulohistiocytosis. Histopathologic and immunophenotypic distinct entities. AB - The clinicopathological and immunohistochemical features of four patients with systemic multicentric reticulohistiocytosis (MR) were compared with five cases of solitary and one case of multiple reticulohistiocytoma (RH), which were confined to the skin only. The MR cases mostly affected the limbs of older women, while RH affected young male adults without preference to site. Characteristically, both entities consisted of oncocytic mononuclear histiocytes (with granular eosinophilic cytoplasm similar to oncocytic thyroid cells) and multinucleated histiocytes with a ground-glass appearance, which appeared to be much larger (> 200 microns) and bizarre in cases of RH compared with cases of MR (50-100 microns). In RH a variable number of vacuolated, spindle-shaped, and xanthomatized mononuclear histiocytes were also present. Immunohistochemical profiles showed positivity of mononuclear histiocytes with HHF35, factor XIIIa, and LN3 (HLA-DR), with a variable number of multinucleated histiocytes in RH showing binding with peanut agglutinin. In mono- and multinucleated histiocytes in both entities macrophage markers KP1 (CD68), KiM1P, HAM56, lysozyme, and alpha 1-antitrypsin were positive. However, macrophage markers MAC387 (L1 antigen) and Leu-M1 (CD15) were negative. Vimentin was universally positive in both conditions, with all other markers (S100, desmin, smooth muscle-specific actin, and QBEnd 10 [CD34]) negative. This study shows that histology supplemented by immunocytochemistry delineates MR from RH and immunohistochemical profiles indicate a cell lineage relationship between RH and adult xanthogranuloma. PMID- 7864295 TI - Fibroepithelioma of Pinkus. Eccrine duct spread of basal cell carcinoma. AB - The spread of basal cell carcinoma (BCC) directly into the dermis or down the sides of hair follicles is a common-place pathologic observation. BCC spread via eccrine ducts, which has received less recognition, is the subject of this investigation. We specifically address the question of whether eccrine duct spread accounts for the histologic pattern of the fibroepithelioma of Pinkus (feP) type of BCC. Twenty-five BCC, including 12 feP, five superficial BCC, six ordinary BCC, one BCC of the sole of the foot, and one BCC with prominent hair follicle spread were studied with H&E sections; 11 were immunostained for carcinoembryonic antigen. In ordinary BCC, occasional entrapped eccrine ducts were present. One superficial BCC surrounded the proximal portion of an eccrine duct. The BCC from the sole of the foot showed advanced spread down eccrine ducts; focal obliteration of duct epithelium and lumen was seen, as was transition to strands of solid BCC. Nine of the 12 feP showed one or several eccrine duct foci with tumor strands. These findings suggest that eccrine ducts serve as an initial template in feP and subsequently are replaced by the BCC. However, eccrine duct spread of BCC may occur without necessarily imparting an feP histologic pattern. PMID- 7864296 TI - Viral glycoproteins in herpesviridae granulomas. AB - Granulomatous reactions after varicella zoster virus (VZV) and herpes simplex virus (HSV) infections are rare, and their pathogenesis remains unclear. We studied by immunohistochemistry and in situ hybridization early granulomatous reactions after VZV and HSV infections. In the five cases studied, the VZV glycoproteins gp I and gp II were present in cells abutted to altered vessels, but the corresponding genome sequences were disclosed in similar locations in only one of these cases. In an immunocompromised patient with diffuse HSV eruption, HSV I antigens were present in cells of the reticular dermis, while viral nucleic acids were not evident. Immunophenotyping of the granulomas showed strong Mac 387 and CD68 positive labelings of macrophages/monocytes, without any involvement of Factor XIIIa-positive cells. These findings suggest that the major viral envelope glycoproteins, rather than complete viral particles could trigger granuloma formation following HSV and VZV skin infections. PMID- 7864297 TI - Estimates of nuclear volume in plaque and tumor-stage mycosis fungoides. A new prognostic indicator. AB - It is well documented that mycosis fungoides (MF), a cutaneous T-cell lymphoma, has a variable clinical course. Unbiased stereological estimates of three dimensional volume-weighted mean nuclear size (nucl vV) of mycosis cells were obtained in a retrospective study of 18 patients with a total of 34 biopsies of cutaneous plaque and tumor-stage MF. The value of nucl vV in the first sampled biopsy, as well as the average and highest values, were determined in biopsies from each patient. The patients were divided into two groups, either above or below the group median. There was a strong positive correlation between shorter survival and an average value of nucl vV > 104 microns 3 or a highest value of nucl vV > 126 microns 3 (2p = 0.002 and 0.003, respectively). A nucl vV > 91.6 microns 3 in the first biopsy was also suggestive of a shorter survival (2p = 0.07). There was no clear pattern of nucl vV evolution in the patients with multiple biopsies, but the impact of various therapeutic regimens cannot be assessed. Certain estimates of nucl vV appear to be good prognostic indicators in plaque and tumor-stage MF, but further study of a larger series of patients is needed to corroborate these results and assess the impact of differing therapeutic regimes. PMID- 7864298 TI - Nuclear morphometry in xeroderma pigmentosum-associated malignant melanomas. AB - Previous clinical observations have indicated that the metastatic potential for thick malignant melanoma is lower for patients with xeroderma pigmentosum than for other patients. In a prospective study using computerized image analysis to measure the morphometric characteristics of nuclei in these neoplasms, we found that the nuclei of malignant melanoma cells were smaller and more ovoid in patients with xeroderma pigmentosum than in other patients. Objective evaluation and grading of these subtle histopathologic variables could provide a means of establishing prognostic factors unrelated to the thickness of the neoplasm. PMID- 7864299 TI - Morphometric, DNA, and proliferating cell nuclear antigen measurements in benign melanocytic lesions and cutaneous malignant melanoma. AB - Morphometric, DNA, and proliferating cell nuclear antigen (PCNA) measurements were taken of benign melanocytic tumors and malignant melanomas. Significant differences between lesion groups according to Krushell-Wallis analysis were found in terms of mean nuclear area, coefficient of variation (cv) of nuclear area, cv of nuclear shape nuclear contour index (NCI), mean and cv of nucleolar area, DNA 2.5 c and 5 c exceeding rates, and PCNA positivity. A logistic regression analysis with respect to banal nevi versus primary malignant melanoma showed that the cv of nuclear area and the DNA 2.5 c exceeding rate were significant independent predictors. Nuclear polymorphism, i.e., the cv of nuclear shape NCI, was larger in metastasizing primary melanomas than in thin nonmetastasizing primary melanomas. PCNA positivity was occasionally increased in keratinocytes adjacent to nevi or melanomas. Larger values for nuclear area, DNA aneuploidy, and PCNA positivity were found in thick malignant melanomas and melanoma metastases than in benign melanocytic lesions and thin malignant melanomas. Morphometry, DNA content, and PCNA positivity thus seem to reflect different stages in tumor progression of malignant melanoma. PMID- 7864300 TI - Condyloma acuminatum associated with syringocystadenoma papilliferum. AB - A 70-year-old man presented with a keratotic lesion of the right buttock. Histologic examination revealed an endophytic cystic and papillary lesion of the dermis. The papillae were lined by two layers of cuboidal epithelial cells with a dense plasmacytic infiltrate of the stroma, consistent with syringocystadenoma papilliferum (SCAP). The overlying epidermis showed acanthosis, papillomatosis, and hyperkeratosis. There were multiple foci of prominent koilocytotic atypia. In situ DNA probes for HPV type 6/11 were positive in many epidermal nuclei. The concurrent occurrence of SCAP and CA may be coincidental; however, the occurrence of CA may be related to the environment at the surface of the SCAP. Syringocystadenoma papilliferum often occurs in association with nevus sebaceus (NS), but it has also been reported from most body sites. When it is not seen in association with NS, the epidermis overlying SCAP may be hyperkeratotic or verrucous. The verrucous changes in our case had features of condyloma acuminatum (CA), which were confirmed by in situ DNA probes. PMID- 7864301 TI - A critical analysis of textbooks of dermatopathology in historical perspective. Part 16. PMID- 7864302 TI - [Tonsillar hirudiniasis. Case report]. AB - Report on a tonsillar parasitosis in a 5-year-old child living in the countryside from leeches of Hirudinea. He consulted because a feeling of foreing body in the throat and spitting of blood, since a fortnight. The AA. remark the low incidence of those cases in our environment. PMID- 7864303 TI - [Otolaryngological complaints in tongue amyloidosis: a case report]. AB - We present a case of Amyloidosis of the oral cavity associated to multiple mieloma, with otolaryngological symptom. Review of structural characterization of the disease, its pathogenesis and clinical disorders when displayed in thyroid, oral cavity and upper respiratory tract. PMID- 7864304 TI - [Occlusion of the internal carotid artery and laterocervical hematoma in a 18 year-old young man]. AB - An eighteen-year-old man was admitted with an espontaneous cervical hematoma. At the operation the occlusion of the internal carotid artery and cervical hematoma was verified. The hematoma was evacuated and the artery ligated. A comment on the different causes of the neck's tumors is presented. No exact etiology for the case reported be ascertain. PMID- 7864305 TI - [The influence of pregnancy on mucociliary nasal transport]. AB - In 30 pregnant healthy women and other 70 healthy but non pregnant the AA. study the mucociliary nasal transport-time, using the charcoal method. The conclusion drawn out is that during the pregnancy the transport-time is meaningly reduced and the pregnants shows characteristic nasal signs and symptoms. PMID- 7864306 TI - [Secondary neoplasms in upper respiratory and digestive tracts]. AB - Patients enduring cancer of the upper respiratory tract present greater risk of developing a second neoplasm, either synchronous or metasynchronously. Possible causes of this major risk are studied, giving a special attention to the role released for the treatment done in the primary neoplasm, in the later appearance of the second one. PMID- 7864307 TI - [The protocol for the vestibulospinal system study by means of a dynamometric platform. Patterns of normalcy]. AB - The Posturography, the recording of the postural balance in standing position, allows the assessment of the vestibulospinal function, through the shifts of the pressure center. In this paper are expressed the results gained with this static posturographic protocol followed at our Department, using a dynamometric platform DINASCAN (Institute of Biomechanics, Valencia, IBv) in 63 normal people. Four parameters (i.e. maximal extent of antero-posterior displacement: lateral wards; full length of the shifting; and the surfaced limited for the changes of the pressure center) in 6 several body positions (Romberg with open and closed eyes; closed eyes and overextended head; closed eyes and right and left cervical turn and standing on only one foot with open eyes) were evaluated. The outcome of the proofs become gradually worsened in accordance with the difficulties of the tests, although there were no differences when considering the results of the proofs with turning or hyperextending the head. Diagnostic possibilities trying dynamometric platforms are considered. PMID- 7864308 TI - [ENT nosocomial infections in the intestinal care unit]. AB - This is a report about the outcome following a study of watchfullness on hospital acquired infections of the E.N.T.-area, during a 7 months term. In the study are included those internees admitted for more than 48 hours in the unit. In each case the clinical record comprises the infective risk factors, the follow-up and treatment, as well as a naso-pharyngo-laryngoscopy with cold light. If necessary cultures and imaging studies were done and even invasive procedures employed with diagnostical and/or therapeutical purposes (punction or surgery). In the whole, a collective of 24 patients, with an average attendance of 17.5 days (margin 3-60 days), average age 54.4 years (margin 22-85 years), 5 nosocomial E.N.T. infections were detected: 2 pansinusitis, 2 bacterial otitis media and 1 case of infected tracheostome. This figures should be related with an incidence rate of 20.8 percent discharges. Cranio-encephalic traumata, the taken of antimycotics and either the simultaneous use of feeding tubes (naso-gastric, naso-jejunal) have had a statistical value as risk factors linked with ENT-area. Discussion on the need for establishing a permanent program of surveillance of ENT-infections in the ICU without missing a routine naso-pharyngolaryngoscopy. PMID- 7864309 TI - [Symptomatic malformations of the first branchial arch]. AB - Congenital malformations of the branchial arches are not infrequent. Among them first branchial cleft anomalies are common and they are to remain asymptomatic. The case reported is one of symptomatic fistula auris, which at the beginning led us to the initial diagnosis of an orbital cellulitis, secondary to ethmoidal sinusitis. We have made a review of the literature dealing with these anomalies and we expose in the paper an update perusal of the clinical features and the management of this rare complication. PMID- 7864310 TI - [Paraneoplastic acrokeratosis (Bazex' syndrome) associated with metastatic adenopathy of the neck from a differentiated carcinoma simultaneous with a well differentiated carcinoma of the oral cavity]. AB - The Acrokeratosis paraneoplastica is a skin pathology sometimes linked with malignancies of the upper respiratory or digestive ways. We report a case of a 71 year-old man enduring and dedifferenciated carcinoma of the parotid gland and metastatic cervical lymph nodes. Perusal of the literature about Bazex's syndrome. PMID- 7864311 TI - The superiority of epidural opioids for postoperative analgesia--fact or fallacy? PMID- 7864312 TI - Age-dependent haematological disturbances in anaesthetic personnel chronically exposed to high occupational concentrations of halothane and nitrous oxide. AB - Anaesthetic staff chronically exposed to high occupational concentrations of halothane and nitrous oxide were tested for numerous haematological and cellular function parameters at the peak of the working season and after 3 weeks vacation. The analysis of data was performed to compare differences in subjects younger and older than the age of 40 years, respectively when compared with normal controls. The analysis revealed a higher recovery of erythrocyte count in the blood of older staff, and stronger disturbance of leucocyte formation in younger staff. In contrast, monocytes appeared to be more stable in the younger staff as were the T and B lymphocyte counts. After stimulation with PHA, Con A and PWM mitogens, lymphocytes from the older age group incorporated a significantly higher amount of tritiated thymidine, but stimulation indices did not differ. Natural killer cell numbers appeared equally affected; natural killer cell activity was unaffected, but there was an increase in activity in the younger staff after the vacation. Serum immunoglobulin concentrations tended to be more affected in older individuals at the peak of the working season. PMID- 7864313 TI - Effect of topical anaesthesia on the motor performance of vocal cords as assessed by tussometry. AB - Tussometry involves a continuous measurement of airflow produced by a cough manoeuvre displayed as an airflow-time wave. There is a rapid rise to its peak (cough peak flow rate) and the time taken to reach the peak (peak velocity time) is determined by the laryngeal opening at the onset of cough. Cough peak flow and peak velocity time were measured in 10 healthy volunteers before and after topical anaesthesia of the larynx with lignocaine 100 mg sprayed under indirect laryngoscopy. Adequacy of anaesthesia was established by touching the cords deliberately with a fibreoptic laryngoscope. All subjects had excellent anaesthesia of the larynx. However, cough peak flow rate and peak velocity time remained unchanged following topical anaesthesia. We conclude that topical anaesthesia of the larynx does not impair the motor performance of the vocal cords during a voluntary cough. PMID- 7864314 TI - A new technique for fibreoptic intubation in children. AB - We describe a technique involving the use of a laryngeal mask airway, fibreoptic bronchoscope and a guide wire to manage the intubation of a child who was known to be a difficult intubation. The technique is simple, atraumatic, permits the use of an adult bronchoscope for infants and children, and allows control of the airway and ventilation throughout the period of intubation. PMID- 7864315 TI - The effect of epidural administration of alfentanil on intra-operative intravenous alfentanil requirements during nitrous oxide-oxygen-alfentanil anaesthesia for lower abdominal surgery. AB - The effects of epidural administration of alfentanil on the intravenous alfentanil dose requirements and the plasma concentrations required to suppress responses to surgical stimulation during nitrous oxide-oxygen-alfentanil anaesthesia in 20 patients undergoing lower abdominal surgery were studied. Before induction of anaesthesia, patients in one group (E) received an epidural injection of 1 mg alfentanil, followed by an epidural infusion of alfentanil 0.2 mg.h-1 until skin closure, whilst patients in the other group (C, control) received a continuous infusion of sodium chloride via a sham catheter in order to blind the main investigator to the treatment. Anaesthesia was induced and maintained with nitrous oxide (66%) in oxygen and a 'target'-controlled intravenous infusion of alfentanil. During surgery, the 'target' alfentanil concentration was increased or decreased according to patients' responses. The number of responses to surgical stimulation was smaller in patients from group E (median 1, range 0-3) than in patients from group C (median 4, range 1-15; p < 0.005), even though the alfentanil intravenous infusion rates were smaller in group E [mean (SD): 1.6(0.5) micrograms.kg-1 min-1] than in group C [2.9(1.2) micrograms.kg-1 min-1, p < 0.02]. Both the lowest concentrations associated with no response [133(40) ng.ml-1] and the highest concentrations associated with a response [155(65) ng.ml-1] in group E were lower than those in group C [238(100) ng.ml-1, p < 0.01 and 334(163) ng.ml-1, p < 0.05, respectively]. We concluded that epidural administration of alfentanil reduces intravenous alfentanil requirements during nitrous oxide-oxygen-alfentanil anaesthesia for lower abdominal surgery. The results indicate a spinal mechanism of action of epidural alfentanil. PMID- 7864316 TI - Right ventricular function and oxygen transport patterns in patients with acute respiratory distress syndrome. AB - We investigated the impact of right ventricular performance on oxygen kinetics in 15 consecutive patients with acute respiratory distress syndrome. Six hundred and twenty-two complete assessments of haemodynamics, right ventricular function and oxygenation were used for evaluation. Patients were grouped as survivors (n = 8) and nonsurvivors (n = 7) and studied during four phases of lung failure. Oxygen delivery and consumption were significantly higher in survivors compared to nonsurvivors despite comparable arterial oxygen saturation. Right ventricular end diastolic volumes were similar for both groups, while end-systolic volumes were significantly higher in nonsurvivors due to depressed ejection fraction (40.5 (SD 1.2) versus 34.4 (SD 2.8)%) during all phases of lung failure. No clinically relevant differences in right ventricular function or oxygenation were observed between periods of moderate or severe pulmonary hypertension. Nonsurvivors have depressed cardiac function caused by reduced contractility and not by inadequate right ventricular end-diastolic volume (preload) or increased pulmonary artery pressure (afterload). Maintenance of oxygen delivery in ARDS is predominantly a function of cardiac performance and not of pulmonary gas exchange. PMID- 7864317 TI - Effect of ketorolac, ketoprofen and nefopam on platelet function. AB - Ketorolac, ketoprofen and nefopam are often used in the treatment of postoperative pain. While nefopam is a non-narcotic, non-opioid central analgesic agent, ketorolac and ketoprofen are non-steroidal anti-inflammatory drugs, which, due to their prostaglandin-synthetase inhibiting activity, have antiplatelet effects. In this study we investigated the effect of ketorolac, ketoprofen and nefopam on platelet function by performing bleeding time and in vitro platelet aggregation in 30 healthy volunteers (10 for each treatment) before and 3 h after drug administration. Nefopam did not affect bleeding time and platelet aggregation, while ketorolac and ketoprofen significantly prolonged bleeding time without significantly inhibiting platelet aggregation in response to adenosine diphosphate. The prolongation of bleeding time observed after ketorolac and ketoprofen may have clinical relevance and suggests that nefopam could be more safely administered for the treatment of postoperative pain, especially in patients with haemostatic defects or after high bleeding risk surgery. PMID- 7864318 TI - Munchausen's syndrome. A case presenting as asthma requiring ventilation. AB - We present a variant of Munchausen's syndrome not previously described in which acute severe asthma is the presenting complaint. The clinical presentation is so extreme that the patient has received artificial ventilation on several occasions despite having had normal arterial blood gas values. The patient appears to be able to mimic the signs of severe respiratory distress by means of a protracted Valsalva manoeuvre, and all signs of acute asthma instantaneously disappear with sedation. Because of the chronic 'asthma', and the frequent dramatic acute episodes, the patient successfully claims invalidity benefit, and has done so for many years. PMID- 7864319 TI - Cardiac tamponade in an infant. A rare complication of central venous catheterisation. AB - A 2994 g infant suffered cardiac tamponade from an infusion of total parenteral nutrition through an indwelling central venous catheter. The infant survived as a result of early diagnosis and aggressive therapeutic intervention. Cardiac tamponade secondary to central venous catheterisation is rare, but potentially lethal. Possible mechanisms are direct puncture by the catheter tip, or osmotic injury from the use of hypertonic solutions. To avoid this complication, the catheter tip should be prevented from entering the right atrium and its position should be checked periodically by chest X ray. Cardiac tamponade should be considered in any patient with a central venous catheter whose clinical condition deteriorates suddenly. Diagnostic or therapeutic pericardiocentesis should be employed as the first measure and time should not be wasted on other diagnostic procedures. PMID- 7864320 TI - Scapular and proximal humeral head fractures. An unusual complication of cardiopulmonary resuscitation. AB - We report a patient who sustained fractures of the scapula and proximal humeral head as a result of cardioversion during cardiopulmonary resuscitation. It is postulated that the fractures were the result of tetanic muscular contractions involving the proximal humeral heads and the shoulder girdles. This appears to be a previously unreported injury. PMID- 7864321 TI - The effect of propofol sedation in pregnancy on neonatal condition. AB - A woman who suffered an intracerebral haemorrhage secondary to Moyamoya disease in her 33rd week of pregnancy was sedated for ventilation with propofol for 48 h until she underwent emergency Caesarean section. There appeared to be no adverse metabolic effects on the neonate from the use of propofol in the mother although sedation was prolonged. PMID- 7864322 TI - Traumatic pneumomyelogram. Implications for the anaesthetist. AB - A 70-year-old man sustained a severe head injury following a fall downstairs, which resulted in him being found in a head down position. In the accident and emergency department he was noted to have subarachnoid air on a lateral cervical spine radiograph. This drew attention to the presence of fractures in the middle cranial fossa and nitrous oxide was immediately discontinued. The presence of a traumatic pneumomylogram implies a base of skull or middle cranial fossa fracture, and is almost certainly associated with intracranial subarachnoid air. Early recognition of the condition, and cessation of nitrous oxide, is essential to prevent dangerous increases in intracranial pressure secondary to the diffusion of gas into the air filled cavity. PMID- 7864323 TI - Forces acting on the maxillary incisor teeth during laryngoscopy using the Macintosh laryngoscope. AB - We determined the forces on the maxillary incisors during routine laryngoscopy in 65 adult patients. The forces were measured by a strain gauge based sensor positioned between the handle and the blade of the laryngoscope. The mean maximal force acting on the maxillary incisors was 49 N. In patients without maxillary incisors, the force acting on the gums was significantly lower at 21 N (p < 0.001). These results suggest that, despite traditional advice to the contrary, a levering movement of the laryngoscope, using the maxillary incisors (or gums) as a fulcrum, is common practice. Biomechanical analysis revealed that, although levering is not the preferred movement, it is an efficient way of bringing the glottis into view. These results may have implications for future laryngoscope design. PMID- 7864324 TI - Accuracy, alarm limits and rise times of 12 oxygen analysers. AB - The Comite Europeen de Normalisation recently proposed a new standard for 'the particular requirements of oxygen monitors for medical use'. The feasibility of this proposed standard was tested in respect of (1) accuracy of alarm activation (2) accuracy of oxygen display value during both continuous and cyclical gas flows (3) rise time during rapid changes in oxygen concentration in the following 12 analysers: Datex Capnomac II and Servomex 570A (paramagnetic); Bruel & Kjaer 1304 (magnetoacoustic); Criticare Poet II, Multinex, Drager Oxydig, Drager PM 8030, Megamed 046A (part of the Megamed 700 ventilator), Ohmeda 5120, Spacelabs Multigas, Teledyne TED 200 (galvanic); Kontron OM 810 (polarographic). All the analysers tested displayed an oxygen reading which was within +/- 3 vol% of the actual oxygen concentrations of the test gases (15, 21, 40, 60 and 100 vol%). A cyclical pressure of between -1.5 to +8 kPa did not affect the measured oxygen concentration as displayed by the Bruel & Kjaer 1304, Datex Capnomac II and Servomex 570A analysers. The remainder, however, showed, depending on their measuring principle, a display error of between -1 and +6 vol%. After exposure to high pressure all the oximeters functioned normally. Some of the tested devices showed more than 2% of deviation between their alarm activation and the preset alarm limits. Only the Kontron OM 810, the Megamed 046A and the Spacelabs Multigas monitors satisfied the requirements at all the tested oxygen concentrations. The time required by the oxygen analyser to display the rise from 29 to 92 vol % after a sudden change of concentration from 21 to 100 vol % O2 is defined as "rise time" and must not, according to the Comite Europeen de Normalisation standard proposal, exceed the manufacturers' specification by more than a factor of 1.15.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864325 TI - Anaesthesia and mucopolysaccharidoses. A review of airway problems in children. AB - The airway problems encountered during anaesthesia in all children with mucopolysaccharidoses presenting for a surgical procedure from 1988 to September 1991 are reviewed. Thirty-four patients underwent 89 anaesthetics for 110 procedures. The results reveal a high incidence of airway problems. The overall incidence of difficult intubation was 25% and failed intubation 8%. In those children with Hurler's syndrome, the difficult intubation incidence was 54% and failed intubation incidence 23%. Other potential anaesthetic problems such as cardiac anomalies and obstructive sleep apnoea are also reviewed. PMID- 7864326 TI - Depth of epidural space in children. AB - We have studied the depth of epidural space in 586 children who had lumbar epidural block as part of their anaesthetic management. The mean depth of epidural space in neonates was 1 cm (SD 0.2, range 0.4-1.5 cm). The depth of epidural space in older infants and children correlated significantly with age and weight with regression equations of depth (cm) = 1 + 0.15 x age (years) and depth (cm) = 0.8 + 0.05 x weight (kg) respectively. PMID- 7864327 TI - Low dose bupivacaine/fentanyl epidural infusions in labour and mode of delivery. AB - The aim of this study was to determine the effect on the instrumental delivery rate of two different concentrations of bupivacaine combined with fentanyl in epidural infusions during labour. Only primiparous women in whom a spontaneous vaginal delivery was anticipated, were included in the study. Those women receiving a higher concentration of bupivacaine and therefore a greater amount of local anaesthetic agent during labour were significantly more likely to have an instrumental delivery with Kielland's rotational forceps (p < 0.01). Those women receiving a lower concentration and smaller amount of bupivacaine were significantly more likely to have an instrumental delivery with Neville-Barnes forceps (p < 0.05). This provides evidence to support the theory that epidural analgesia may contribute to inadequate rotation of the presenting fetal part due to weakened pelvic floor muscles and that this is more likely to occur when higher concentrations of bupivacaine are used and a greater degree of motor block occurs. PMID- 7864328 TI - A trial of pre-emptive analgesia. Influence of timing of peroperative alfentanil on postoperative pain and analgesic requirements. AB - The influence of timing of administration of peroperative alfentanil on pain and analgesic requirements after surgery was studied in 60 patients undergoing total abdominal hysterectomy with or without bilateral salpingo-oophorectomy. Thirty patients received alfentanil 7.5 micrograms.kg-1 on induction of anaesthesia, followed by alfentanil 7.5 micrograms.kg-1 90 s before surgical incision (group A). Thirty control patients received alfentanil 15 micrograms.kg-1, 10 min after abdominal incision (group B). In addition, 10 min after surgical incision both groups received morphine 0.2 mg.kg-1, given over a 10 min period. The visual analogue scores (median, interquartile range) for pain 24 h after operation were 28.5 mm (11.25-47.0) in group A and 21.0 mm (10.5-47.5) in group B, p = 0.76. There were no differences in visual analogue scores at intermediate times. Morphine consumption in the first 24 h after surgery (median, interquartile range) was 53.5 mg (37.25-60.0) in group A and 52.0 mg (39.75-71.0) in group B, p = 0.52. We conclude that postoperative morphine consumption and pain scores are no different when alfentanil 15 micrograms.kg-1 is given before or after skin incision for abdominal hysterectomy. PMID- 7864329 TI - How useful is spinal anaesthesia in day case surgery? PMID- 7864330 TI - Airway management during percutaneous dilatational tracheostomy. PMID- 7864331 TI - Correct tracheal tube placement. PMID- 7864332 TI - Capnography for teaching airway management. PMID- 7864333 TI - Capnography in babies and small children. PMID- 7864334 TI - Respiratory monitoring for regional anaesthesia. PMID- 7864335 TI - An unusual complication of the laryngeal mask airway? PMID- 7864336 TI - Introducing the re-inforced laryngeal mask airway. PMID- 7864337 TI - Waiting lists in pain clinics. PMID- 7864338 TI - Cricoid pressure. PMID- 7864339 TI - Wanted. A psychologist's view of drug packaging. PMID- 7864340 TI - Condensation. PMID- 7864341 TI - Product label information for suxamethonium in the USA. PMID- 7864342 TI - Problem with soda lime. PMID- 7864343 TI - Radial artery occlusion detected by pulse oximetry. PMID- 7864344 TI - Near infrared oximetry and near infrared spectroscopy. PMID- 7864345 TI - Problems with an incorrectly assembled disposable anaesthetic breathing system. PMID- 7864346 TI - Explosion of tracheal tube during tracheostomy. PMID- 7864347 TI - Patients' knowledge of anaesthesia. PMID- 7864348 TI - A migrating central venous catheter. PMID- 7864349 TI - An unusual case of failure to ventilate the lungs. PMID- 7864350 TI - 'Heparin analgesia'. PMID- 7864351 TI - Immunotargeting intracellular compartments. PMID- 7864352 TI - Prokaryotic test system for evaluation of oligonucleotide-affected antisense inhibition. AB - A new test system is introduced for the estimation of the antisense effect of various types of oligodeoxy-nucleotides. This system is based upon the inhibition of translation of P2 phage repressor protein. Evidence for a direct correlation between phage yield and antisense inhibition was obtained by comparing the concentration-dependent effectiveness of an antisense phosphorothioate 18-mer, its mutated version, and the unmodified oligonucleotide. Oligonucleotides of complementary sequences were synthesized against the ribosome binding site and different sites of the coding region. In our test system only small differences were found based on the location of the target sequence. Rather, the degree of inhibition was related to the calculated ability to hybridize based on Tm values. In this way the sensitivity of the test system could also be demonstrated. PMID- 7864353 TI - Solving buffering problems with Mathematica software. AB - Determining ionic concentrations in buffered solutions usually reduces to solving a set of simultaneous polynomial equations. Mathematica software offers a convenient method for doing this. Using buffering of Ca2+ by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) as an example, we provide a Mathematica script to estimate the apparent association constant. A second example shows how to calculate free ion concentrations when two ligands (Ca2+ and Mg2+) compete for one chelator (EGTA). Finally, the concentrations of all species are determined in a complex mixture containing Ca2+, EGTA, and calmodulin, a protein with four Ca(2+)-binding sites. Modifying the examples presented should allow analysis of most practical buffering problems. PMID- 7864354 TI - High-resolution separation of recombinant human interferon-gamma glycoforms by micellar electrokinetic capillary chromatography. AB - Recombinant human interferon-gamma (IFN-gamma) glycoform populations produced by Chinese hamster ovary cells have been resolved by micellar electrokinetic capillary chromatography (MECC). Separations were performed in uncoated fused silica capillaries at alkaline pH in the presence of micellar concentrations of the anionic detergent sodium dodecyl sulfate (SDS). Maximum resolution was obtained reproducibly with high-ionic-strength borate/SDS electrophoresis buffer. Under the conditions described, glycoform migration time was inversely related to the amount of carbohydrate associated with the protein. Digestion of IFN-gamma with peptide-N-glycosidase F allowed virtual real-time monitoring of glycosidase digests by capillary electrophoresis. Analysis of other digestions with either neuraminidase or endoglycosidase H (endo H) showed most IFN-gamma glycoforms to be sialylated and a minor proportion of glycoforms to be associated with oligomannose structures. While both bovine pancreas ribonuclease B and horse radish peroxidase glycoforms were separated by this technique, proteins glycosylated at multiple sites such as bovine serum fetuin and human alpha 1-acid glycoprotein were not well resolved by MECC. PMID- 7864355 TI - Simultaneous monitoring of the environment of tryptophan, tyrosine, and phenylalanine residues in proteins by near-ultraviolet second-derivative spectroscopy. AB - A method for deconvolution of the near-uv second-derivative spectra of proteins into their component tryptophan, tyrosine, and phenylalanine spectra is described. In this approach, the second-derivative spectra of tryptophan and tyrosine model compounds are numerically shifted to create a set of reference spectra corresponding to anticipated peak positions in protein environments of different polarity. The relative contributions of these individual standard spectra are varied until the best fit to the experimental protein spectrum is obtained. Separate addition of tryptophan and tyrosine standard spectra, weighted by their contributions as determined in the fitting procedure, yields an accurate representation of the spectra of these residues in proteins. The position of the intersection of these spectra with the wavelength axis is used as a measure of spectral position in ethylene glycol perturbation experiments in which the average solvent accessibility is assessed by relating the observed shifts in the tryptophan and tyrosine spectra to the shifts observed for corresponding model compounds. The phenylalanine peak positions in the set of 16 proteins studied are determined as described previously [H. Mach et al. (1991) Arch. Biochem. Biophys. 287, 33-40]. For all three aromatic residues in proteins, no consistent correlation between absolute spectral band positions and average solvent accessibility is observed, suggesting a significant influence of other local (e.g., electrostatic) effects on near-uv spectra of proteins. The maximum spectral shift observed between solvent-exposed model compounds and side chains entirely buried in apolar protein core was found to be approximately 5 nm for tyrosine, 4 nm for tryptophan, and 2 nm for phenylalanine residues. PMID- 7864356 TI - Sequential determination of triglycerides and free fatty acids in biological fluids by use of a continuous pretreatment module coupled to a gas chromatograph. AB - A continuous system coupled to a gas-liquid chromatograph was used for the sequential determination of triglycerides and free fatty acids in serum and urine. The module provides compositional information and hence more detailed information on lipid metabolism changes in patients suffering metabolic disorders. Lipids in biological samples are manually extracted in methanol-n hexane and introduced into the flow system; free fatty acids are then separated by retention on an ion-exchange resin and triglycerides (not retained) are transesterified with acetyl chloride in methanol. The resulting methyl esters are continuously injected into the gas chromatograph and determined by using a flame ionization detector. In a second step, retained free fatty acids are eluted and derivatized (also with acetyl chloride in methanol) and subsequently determined similarly as the triglycerides. The proposed method was applied to the determination of triglycerides in a lipid control serum; free fatty acids were determined in a human pool serum by the proposed method and compared with the volumetric method used in clinical practice. The results obtained in both instances showed good agreement between the results provided for triglycerides and free fatty acids. The proposed method was also applied to urine samples; a parallel recovery study was also made in order to assess the performance of the method. PMID- 7864357 TI - A rapid and selective endothelin-converting enzyme assay: characterization of a phosphoramidon-sensitive enzyme from guinea pig lung membrane. AB - Endothelin-1 (ET-1) is the most potent vasoconstrictor hormone known to date. Biosynthesis of ET-1 from its precursor big endothelin-1 (BET-1) is mediated by endothelin-converting enzyme (ECE), a phosphoramidon-sensitive metalloprotease. We have established a simple, rapid, and selective assay for the evaluation of ECE activity. This assay is based on the quantitative determination of [125I]ET-1 released from (3-[125I]idotyrosyl13)BET-1 by binding to the membrane-bound endothelin (ET) receptor. Using this assay we have discovered that guinea pig lung membrane (GPLGM) contains a phosphoramidon-sensitive ECE. Treatment of GPLGM with 0.06% lubrol increased ECE activity and ET binding of the membrane preparation. Lubrol-treated GPLGM (L-GPLGM) contains a high density of ET binding sites (Bmax = 2000 fmol/mg protein) and shows no proteolytic activity for degredation of ET-1. At protein concentrations suitable for measurement of ECE activity (0.2 mg/ml), L-GPLGM contains a high concentration of ET receptors and shows a rapid rate of ET-1 binding to the membrane preparation (binding equilibrium in < 5 min). Thus, we have utilized L-GPLGM preparation for both ECE activity and measurement of ET-1 binding in a single-step assay for the determination of enzyme activity. ECE activity of L-GPLGM was fully inhibited by phosphoramidon, 1,10-phenanthroline, and EDTA. Class-specific inhibitors of serine, cysteine, and aspartic proteases showed no significant effect on ECE activity in L-GPLGM. These results show that GPLGM contains exclusively a phosphoramidon-sensitive ECE. PMID- 7864358 TI - Colorimetric determination of DNase I activity with a DNA-methyl green substrate. AB - A simple, high throughput, and precise assay was developed for quantification of deoxyribonuclease I (DNase; IUB 3.1.21.1) activity. The method was adapted from the procedure devised by Kurnick which employs a substrate comprised of highly polymerized native DNA complexed with methyl green. Hydrolysis of the DNA produced unbound methyl green and a decrease in the absorbance of the solution at 620 nm. By adjusting the time and temperature of the reaction, the assay permits quantification of DNase activity over a wide concentration range (0.4 to 8900 ng/ml). Samples and standards were added to the substrate in microtiter plates and were incubated for 1-24 h at 25-37 degrees C to achieve the desired assay range. The DNase activity of the samples was interpolated from a standard curve generated with Pulmozyme recombinant human deoxyribonuclease I (rhDNase). Interassay precision was less than 12% CV and recovery was within 100 +/- 11%. Activity determination by the DNA-methyl green method correlated well with that determined by the widely used "hyperchromicity" method originated by Kunitz, which is based on the increase in absorbance at 260 nm upon hydrolysis of DNA. The DNA-methyl green assay was simpler and more versatile than the hyperchromicity method and was used to characterize the activity of rhDNase and DNase isolated from human urine. PMID- 7864359 TI - A multiple assay for vitamin D metabolites without high-performance liquid chromatography. AB - We describe a multiple assay of the three main vitamin D metabolites, 25OHD, 24,25(OH)2D, and 1,25(OH)2D, in 0.5 ml of serum, which does not require high performance liquid chromatography. The assay involves extracting the serum with acetonitrile, separation and purification on a C-18/OH cartridge and a Sep-Pak silica cartridge, and quantitation using 1,25(OH)2D receptors from calf mammary gland for 1,25(OH)2D, and vitamin D binding protein for 25OHD and 24,25(OH)2D. For 25OHD, 24,25(OH)2D, and 1,25(OH)2D, the method is sensitive to 0.125 ng/tube, 0.025 ng/tube, and 0.5 pg/tube, with the B50 occurring at 1 ng/tube, 0.2 ng/tube, and 8 pg/tube, respectively. The coefficients of variation (SD/mean x 100%) intraassay (n = 8) were 5.4, 12.8, and 6.6% and interassay (n = 6) 12.3, 10.8, and 8.6%. The overall recovery was 80.4 +/- 5.5, 58.0 +/- 6.3, and 77.4 +/- 5.6% (mean +/- SD, n = 40). The validity of the assay was confirmed by dilution test, analytical recovery of added vitamin D metabolites, and comparison with a standard assay using HPLC. This assay offers a simple, rapid, and precise method with which to determine the three main vitamin D metabolites in small serum samples, so it should be particularly useful in studies of pediatrics or small animals. PMID- 7864360 TI - Reduced-scale large-zone analytical gel filtration chromatography for measurement of protein association equilibria. AB - The method of large-zone analytical gel filtration chromatography (AGFC) for determination of the energetics and stoichiometries of protein association processes was adapted for use with a semicompressible hydrophilic sieving resin and high-performance liquid chromatography (HPLC) instrumentation. Chromatography was performed using a 2.3-ml glass column, providing a 10-fold reduction in column volume over the conventional AGFC low-pressure chromatography format. Equipment consisted of a Teflon injection valve, HPLC pump, and uv-vis spectrophotometric detector. Method validation included preparation of calibration curves using data obtained from small- and large-zone chromatography of monomeric protein standards. Following confirmation of the agreement of small- and large-zona data obtained for monomeric proteins, the method was further tested by measurement of the dimer-tetramer equilibrium constant for the well characterized oxygenated human hemoglobin system. Excellent agreement between the experimentally determined equilibrium association constant and the literature value was obtained, as well as a dramatic savings in material and time required to perform the experiment. PMID- 7864361 TI - Extraction and assay of creatine phosphate, purine, and pyridine nucleotides in cardiac tissue by reversed-phase high-performance liquid chromatography. AB - The levels of creatine phosphate, purine, and pyridine nucleotides in tissues provide important information on energetic and oxidative cellular states. Nevertheless, technical, theoretical, and methodological difficulties in extraction and quantification procedures have so far limited our understanding of the exact role that these substances play in metabolic processes which take place in cells. The objective of our study was to find an easy and rapid method for extracting, separating, and quantifying creatine phosphate, purine, and pyridine nucleotides in solid tissues. We adapted the classic acid-extraction procedure with HClO4 for purine and oxidized pyridine nucleotides and then developed a new alkaline extraction with phenol in a phosphate buffer solution (pH 7.8) for reduced pyridine nucleotides. Biopsies of myocardial tissue were frozen and ground at -180 degrees C using the appropriate extraction procedure. The separation and quantification of the metabolites were performed using a reversed phase 3-microns Supelchem C18 column, with the addition of tetrabutylammonium as an ion-pair agent to the buffer solution, by ultraviolet detection. The recovery of the external and internal standards always exceeded 90%. The autooxidation or interconversion processes were almost insignificant for each reduced form. This technique allowed us to avoid complex enzymatic procedures and difficulties in the selective assay of pyridine nucleotides with chemiluminescence and surface spectroscopy. PMID- 7864362 TI - Polymer networks with grafted cell adhesion peptides for highly biospecific cell adhesive substrates. AB - Polymer networks of poly(ethylene glycol) (PEG) in densely cross-linked matrices of acrylic acid (AA) and trimethylolpropane triacrylate were synthesized as biospecific cell adhesive substrates. Networks grafted with synthetic adhesion peptides produced substrates to investigate long-term, receptor-mediated cell/surface interactions, without nonspecific protein adsorption producing spurious adhesion signals. PEG rendered the networks very resistant to cell adhesion in vitro, and AA provided reactive carboxyl moieties for N-terminal grafting of peptides. Networks with higher mass fractions of AA had greater background cell adhesion, which diminished with higher mass fractions of PEG such that complete resistance to cell adhesion could be obtained. Networks grafted with inactive control peptides (GRGES or no peptide) remained completely cell nonadhesive in the presence of serum or even when preincubated with adhesion proteins, while networks grafted with bioadhesive peptides (GRGDS, GYIGSRY, or GREDVY) supported morphologically complete fibroblast adhesion. The amount of AA in the network readily controlled the amount of incorporated peptide. These networks may be suitable as analytical tools specifically to investigate long term cell/substrate interactions in the presence of serum, yet without non specific protein adsorption producing adhesion signals other than those immobilized for study. PMID- 7864363 TI - Electrophoresis for genotyping: microtiter array diagonal gel electrophoresis on horizontal polyacrylamide gels, hydrolink, or agarose. AB - Electrophoresis of DNA has been performed traditionally in either an agarose or acrylamide gel matrix. Considerable effort has been directed to improved quality agaroses capable of high resolution, but for small fragments, such as those from polymerase chain reaction (PCR) and post-PCR digests, acrylamide still offers the highest resolution. Although agarose gels can easily be prepared in an open-faced format to gain the conveniences of horizontal electrophoresis, acrylamide does not polymerize in the presence of air and the usual configurations for gel preparation lead to electrophoresis in the vertical dimension. We describe here a very simple device and method to prepare and manipulate horizontal polyacrylamide gels (H-PAGE). In addition, the open-faced horizontal arrangement enables loading of arrays of wells. Since many procedures are undertaken in standard 96-well microtiter plates, we have also designed a device which preserves the exact configuration of the 8 x 12 array and enables electrophoresis in tracks following a 71.6 degrees diagonal between wells (MADGE, microtiter array diagonal gel electrophoresis), using either acrylamide or agarose. This eliminates almost all of the staff time taken in setup, loading, and recordkeeping and offers high resolution for genotyping pattern recognition. The nature and size of the gels allow direct stacking of gels in one tank, so that a tank used typically to analyze 30-60 samples can readily be used to analyze 1000-2000 samples. The gels would also enable robotic loading. Electrophoresis allows analysis of size and charge, parameters inaccessible to liquid-phase methods: thus, genotyping size patterns, variable length repeats, and haplotypes is possible, as well as adaptability to typing of point variations using protocols which create a difference detectable by electrophoresis. PMID- 7864364 TI - Kinetic study of the malonaldehyde-azulene reaction determination of malonaldehyde in human plasma. AB - The influence of physicochemical conditions in the formation of derivatized malonaldehyde (MLD)-azulene was studied, and kinetic and conventional spectrophotometric data were compared. Conventional and kinetic spectrophotometric procedures were used to study inference of several compounds. An advantageous kinetic method was used to determine MLD in human plasma. The proposed method is faster than the thiobarbituric acid (TBA) method, because 150 s is sufficient to develop the reaction and the kinetic measurements. A comparative study of the results obtained using the proposed kinetic method and those reported in the literature for MLD determination by using the TBA reaction is presented. PMID- 7864365 TI - A method for the determination of the cellular phosphorylation potential and glycolytic intermediates in yeast. AB - A method is described for rapidly quenching metabolism in yeast and extracting metabolites for analysis. The saponin digitonin is used to permeabilize the yeast cell membrane, in conjunction with perchloric acid (PCA) to quench metabolism and extract metabolites. Using this digitonin-PCA quench and extraction procedure, we have determined ATP concentrations in Saccharomyces cerevisiae in the range 2.89 3.39 mM, [ATP]/[ADP] ratios of 4.5-6.6, and phosphorylation potentials of 48.7 49.9 kJ.mol-1. A direct comparison with the currently accepted freeze/grind PCA/thaw procedure for extraction of yeast cell metabolites shows that essentially the same values are obtained by both techniques. The digitonin-PCA quench extraction method, used in conjunction with automated enzymatic analyses of metabolites, allows rapid extraction and analysis of large numbers of samples and metabolites and hence permits detailed investigations of intermediary metabolism in yeast. PMID- 7864366 TI - Analysis by electrospray mass spectrometry of glycopeptides from the in vitro O glycosylation reaction using human mucin motif peptide. AB - A mucin-motif peptide in the one-letter code T T T P S P P M T T P I T P P A, representative of the human intestinal mucin tandem repeat sequence (MUC2), containing several threonine residues in clusters, was used as an acceptor substrate to investigate the effect of peptide structure on the activity of crude preparation of human gastric UDP-GalNAc:polypeptide N-acetyl galactosaminyltransferases. High-performance liquid chromatography was performed to separate the different products of the in vitro O-glycosylated reaction. The electrospray mass spectrometry was used to identify the different masses (m/z) of these products. Although the m/z of glycopeptide(s) could be higher than the detection limits of the spectrometer, an accurate study of the doubly charged ions allowed us to demonstrate the linkage of more than two sugars. Hence, the peptide MUC2 will accept at least four carbohydrate residues but the exact substituted positions should be confirmed by further sequence determination. PMID- 7864367 TI - Single extraction method for the spectrophotometric quantification of oxidized and reduced pyridine nucleotides in erythrocytes. AB - A simplified and reliable assay for the determination of erythrocyte pyridine nucleotide (NAD and NADP) concentrations, as well as the ratio of the reduced [NADH/NADPH] to oxidized [NAD+/NADP+] nucleotide, is important in understanding both normal and abnormal red blood cells (RBC). However, previously published methods for quantitating pyridine nucleotides are inappropriate for RBC, difficult to use, or inaccurate. The method described within this paper provides for both improved reliability and ease of use. In addition, we have documented that significant pools of NADPH and NADH are tightly bound to proteins (e.g., catalase) and not detectable by many of the assay systems previously used. This results in a significant change in not only total RBC pyridine nucleotide content but also in the ratio of reduced to nonreduced nucleotide. PMID- 7864368 TI - Development of a density gradient ultracentrifugation technique for the resolution of plasma lipoproteins which avoids apo E dissociation. AB - A density gradient ultracentrifugation technique for analyzing and isolating plasma lipoproteins was developed that was simple to set up, allowed for the isolation of the plasma lipoproteins in one centrifugal spin, and avoided the dissociation of apolipoprotein E from high-density lipoprotein (HDL) which can occur when plasma is subjected to ultracentrifugation at high concentrations of salt. The density gradient emphasized the resolution of the HDL density region while still enabling the separation of low-density and very low-density lipoprotein. PMID- 7864369 TI - A fluorescence-based assay for human type II phospholipase A2. AB - A fluorescence assay for quantitation of human Type II Phospholipase A2 activity is described. Hydrolysis of 1-Acyl-2-(N-4-nitrobenzo-2-oxo-1,3 diazole)aminododecanoyl Phosphatidylethanolamine is accompanied by an increase in fluorescence intensity that is linearly proportional to enzyme activity. Substrate is prepared in the absence of detergents as a sonicated dispersion in aqueous buffer. Hydrolysis of the corresponding phosphatidylcholine derivative is more than an order of magnitude slower under identical assay conditions. A plot of initial rate versus substrate concentration could be fit to a simple Michaelis Menten relationship with Km = 13 microM. In contrast to commonly used radiochemical assays for this enzyme, the method described here is continuous and allows estimation of enzyme activity without separation of substrate from product. Thus, the method is suitable for both kinetic analysis and large-scale screening using automated readers for 96-well tissue culture plates. The fluorescence-based assay displays advantages over other continuous assays for human Type II Phospholipase A2 based on (a) high sensitivity and (b) the use of a commercially available substrate. PMID- 7864370 TI - Binding of biotinylated DNA to streptavidin-coated polystyrene latex. AB - The binding of 5'-end biotinylated DNA fragments was compared between streptavidin (SA)-coated commercial M-280 magnetic latex particles with a diameter of 2.8 microns and adsorption-coated polystyrene (PS) latex standard particles whose diameter is 0.272 microns. Amino acid analysis showed the protein content of the commercial particles to correspond to 4x monolayer coverage, while the adsorption-coated PS particles displayed monolayer coverage, or 8 pmol/cm2. A fluorescence-based method was developed to quantify the adsorption of FITC labeled SA, biotin, and biotinylated DNA. The validity of the method was substantiated for the labeled protein by both amino acid analysis and a colorimetric protein assay. While the specific binding of biotin was 0.38 mol per mole of SA on the adsorption-coated 0.272-microns particles and slightly higher (0.6 mol per mole SA) on the 2.8-microns particles, the specific binding of the bulky biotinylated 300-bp DNA was more favorable on the smaller particle (0.12 mol per mole SA for 0.272 microns versus 0.04 mol per mole SA for 2.8 microns). PMID- 7864371 TI - A continuous spectrophotometric assay for ureidoglycolase activity with lactate dehydrogenase or glyoxylate reductase as coupling enzyme. AB - A spectrophotometric assay for ureidoglycolase activity (both ureidoglycolate lyase and hydrolase), based on the reduction of glyoxylate to glycolate catalyzed by glyoxylate reductase or lactate dehydrogenase with the stoichiometric and continuous NADH oxidation, is described. The assay has been optimized for the amount of coupling enzyme, reagent concentrations, buffers, and the nonenzymatic degradation of ureidoglycolate. Under optimal assay conditions, ureidoglycolase activity can be followed with either lactate dehydrogenase or glyoxylate reductase as coupling enzyme and reaction can be started by addition of substrate or enzyme extract. Once the reaction was started, NADH oxidation was linear with time after a lag phase of 1-2 min. This linear NADH oxidation was directly proportional to enzyme concentration in the assay mixture until changes in absorbance of 0.12 per minute. This method is easy and reliable for the accurate determination of ureidoglycolase activity in crude and purified extracts from Chlamydomonas reinhardtii cells and no notable interferences have been detected. Since lactate dehydrogenase is much cheaper and has a lower Km for its substrate than glyoxylate reductase and can be used as supplied, its use as the coupling enzyme of choice is recommended. PMID- 7864372 TI - Differential suppression of background mammalian lysosomal beta-galactosidase increases the detection sensitivity of LacZ-marked leukemic cells. AB - A method is described for the detection of Escherichia coli beta-galactosidase expressing leukemic cells in ex vivo bone marrow samples. 4-Methylumbelliferyl beta-D-galactopyranoside is used as a substrate in a kinetic assay. D-Galactose is used to suppress endogenous lysosomal beta-galactosidase activity, yielding a sixfold increase in sensitivity. With this assay, the detection limit is one leukemic cell per 10(4) normal bone marrow cells. PMID- 7864373 TI - A turbidometric assay for phospholipase C and sphingomyelinase. AB - We describe a simple turbidometric assay for phosphatidylcholine-specific phospholipase C (PC-PLC) (EC 3.1.4.3), phosphatidylinositol-specific phospholipase C (PI-PLC) (EC 3.1.4.10), and sphingomyelinase (SMase) (EC 3.1.4.12), suitable for high-volume screening using unmodified substrates. Under the conditions described, 1 to 10 U/ml of PC-PLC (Bacillus cereus) induces a rapid and continuous increase in turbidity (0.4 to 0.6 AU at 410 nm) of phosphatidylcholine vesicles (1-10 mM) that highly correlates with hydrolysis. Turbidity increases with the formation of small homogenous particles, which is enzyme and substrate dependent. Analogously, PI-PLC (1-10 U/ml) causes a continuous increase in the turbidity of PI vesicles. SMase also causes a continuous increase in PC vesicle turbidity, but unlike like the glycerol phospholipases, SMase causes a discontinuous increase in vesicles of its proper substrate sphingomyelin (SM). After 8-15% hydrolysis, SM vesicles are converted to large heterogeneous particles permitting detection of SMase activity by visual inspection. Thus, turbidity is a useful property to monitor SMases and C-type phospholipases that cleave vesicle-forming phospholipids. Furthermore, the assay is designed for the microtiter plate format, enabling the continuous and simultaneous monitoring of up to 96 wells. PMID- 7864374 TI - Colorimetric phospholipid determination with erythrosin B. AB - Binding of phospholipid vesicles to erythrosin B results in a shift of the absorption maximum of the dye from 528 to 549 nm. This effect was employed to develop a simple, rapid, and sensitive quantification method for unilaminar phospholipid vesicles. At room temperature the color development of the phospholipid-dye complex at 549 nm is essentially complete in 5 min and only a slight decrease is observed in the following hours. The pH optimum of 4.5 for the assay is related to the tight binding at this pH (Kd = 3.6 micrograms/ml). A maximal binding of one erythrosin to seven phospholipid molecules is found. The sensitivity of the assay is high for zwitterionic phospholipids (e.g., 0.023 delta A549 x ml/micrograms for dioleoyl phosphatidyl choline) and lower for anionic phospholipids. The assay depends on the size of the phospholipid liposomes, indicating the importance of the phospholipid surface area for binding. PMID- 7864375 TI - Quantitative characterization of bovine plasminogen binding to caseins. AB - The binding of bovine plasminogen to whole casein, alpha s-casein, beta-casein, and kappa-casein is responsible for the progressive proteolysis of milk and dairy products. A sensitive and accurate microparticle-enhanced nephelometric immunoassay was developed to measure free plasminogen after interaction between bovine plasminogen and caseins and the quantitative parameters of plasminogen/casein binding were established. Two classes of binding sites for plasminogen were found in this study on each of the investigated caseins. Their dissociation constants (Kd) were determined by varying the plasminogen concentration at pH 6.6 and performing Scatchard analysis. The two binding sites appeared to be one of high affinity (Kd = 32 nM) and the other of lower affinity (Kd > 370 nM). The number of both binding sites per casein monomer was low (0.04 to 0.53). The great propensity of casein monomers to self-associate in homopolymers where plasminogen binding sites could be hidden and in copolymers present in bovine milk in the form of whole casein micelles accounts for calculated binding sites < 1 per monomer. PMID- 7864376 TI - Preparation of high-molecular-weight DNA: application to mycobacterial cells. AB - A method for isolating high-molecular-weight DNA from bacteria is described. A special feature of the method is the treatment of whole bacterial cells with an organic solvent (chloroform-methanol (2:1, v/v) or ethanol-ether (1:1, v/v)) prior to DNA extraction from the cells. The DNA preparations obtained from organic solvent-pretreated bacterial cells such as Mycobacterium smegmatis, M. phlei, and Escherichia coli contained highly polymerized DNA, as revealed by pulse-field gel electrophoresis. The size and yield of the DNA obtained from E. coli pretreated with the organic solvent were quite similar to that of the DNA obtained from protoplasts. The results strongly suggest that the organic solvent pretreatment is effective for extracting very large DNA from bacterial cells and especially from bacteria whose protoplasts cannot be easily formed. PMID- 7864377 TI - Sugar binding polymers showing high anomeric and epimeric discrimination obtained by noncovalent molecular imprinting. AB - Noncovalent molecular imprinting of sugar compounds in ethylene glycol dimethacrylate-methacrylic acid copolymers yielded materials containing highly selective sugar binding sites. Investigation of a range of polymers demonstrated that the resulting polymer imprints have a high degree of both anomeric and epimeric selectivity favoring the original print molecule. In HPLC assays, a polymer imprinted using p-nitrophenyl-alpha-D-galactoside could separate the alpha and beta anomers of the same compound with near baseline resolution. A polymer imprinted using p-nitrophenyl-beta-D-galactoside showed similar results but with the beta anomers retained longer as expected. Anomeric discrimination of closely related sugars was also possible, with the degree of separation depending on the structural resemblance to the print molecule. Similarly, a polymer imprinted with p-nitrophenyl-alpha-L-fucoside could separate alpha/beta mixtures of p-nitrophenyl-L-fucoside with baseline resolution. Using radioligand displacement assays a polymer imprinted using octyl-alpha-D-glucoside was shown to bind methyl-alpha-D-glucoside with a 40-fold higher affinity than that for the beta-anomer. The epimeric selectivity was even more impressive: methyl-alpha-D mannoside and methyl-alpha-D-galactoside had 130- and 240-fold lower affinity, respectively, than methyl-alpha-D-glucoside. The results are discussed in relation to possible uses of such polymers in separation and analysis. PMID- 7864378 TI - Quantification of free sphingosine in cultured cells by acylation with radioactive acetic anhydride. AB - A simple and sensitive method for quantification of sphingosine in cellular lipid extracts was developed. The assay is based on quantitative conversion of sphingosine to N-[3H]acetylated sphingosine ([3H]C2-ceramide) by N-acylation with [3H]acetic anhydride under certain conditions. Sphingosine was extracted from cultured cells with chloroform and methanol and then treated with base to remove interfering glycerolipids having reactive amino groups (e.g., phosphatidylethanolamine or phosphatidylserine). Sphingosine was acylated with [3H]acetic anhydride in the presence of 0.004 N NaOH. Acylation was complete in 1 h at 37 degrees C when sphingosine was present in the picomole range. After the acylation, samples were treated with NaOH to reduce background radioactivity by removing the remaining [3H]acetic anhydride and hydrolyzing any ester linkages formed during the acylation and resolved by thin-layer chromatography. [3H]C2 ceramide converted from sphingosine with the acylation was detected with radioautography and quantitated by scraping the corresponding band and counting its radioactivity with a scintillation counter. [3H]C2-ceramide formed was quantitatively measured. This assay allows quantification of sphingosine over a range of 10 to 1500 pmol. The amount of sphingosine in lipid extracts from cultured cells was proportional to the number of cells. Sphingosine levels in human gastric cancer KATO III cells, human promyelocytic leukemic HL60 cells, and human monoblastic U937 cells, determined by this method, were 26.6 +/- 2.2, 6.3 +/- 0.4, and 6.8 +/- 0.6 pmol per 10(6) cells, respectively. Our new procedure allows quantification of sphingosine levels present in the low picomole range in lipid extracts from biological samples. PMID- 7864379 TI - alpha 2-8 Sialic acid polymers: size, structure, and compositional analysis. AB - A series of three variable assay procedures is described to provide overlapping information on the size, structure, and composition of the alpha 2-8 linked polysialic acid chains present on a wide variety of critical cell surface glycoproteins. Technical advances in instrumentation have permitted the development of new applications for a methodology involving the sequential use of periodate and borohydride to modify terminal sialic acid residues. The procedures described here provide a rapid and facile assay for (a) the determination of polysialic acid chain length, (b) the simultaneous identification of N acetylneuraminic acid, N-glycolyneuraminic acid, and KDN (deaminated sialic acid) when present in a single preparation, (c) the ability to distinguish qualitatively between reducing and nonreducing polymers, and (d) the ability to determine the number of chains bound to a glycoprotein of known molecular weight. PMID- 7864380 TI - Detection of lipase activity on ultrathin-layer isoelectric focusing gels. PMID- 7864381 TI - The purification of histones by metal-chelate chromatography. PMID- 7864382 TI - Identification of human mitochondrial DNA fragments corresponding to the genes for ATPase, cytochrome C oxidase, and nine tRNAs in a denaturing gradient gel electrophoresis system. PMID- 7864383 TI - A high-yield modification of mutation by overlap extension using three primers. PMID- 7864384 TI - A protease assay via precolumn derivatization and high-performance liquid chromatography. PMID- 7864385 TI - A nonseparation microplate receptor binding assay. PMID- 7864386 TI - Wavelength-resolved fluorescence detection in capillary electrophoresis. AB - A multichannel laser-induced fluorescence detector for capillary electrophoresis is described. The detection system combines yoctomole limits of detection with the simultaneous acquisition of entire fluorescence emission spectra. An Ar/Kr mixed-gas ion laser provides great flexibility in excitation wavelengths, and a holographic grating and charge-coupled device detector combination allows a 500 nm spectral window to be acquired with 2-nm resolution. The limits of detection are 5 x 10(-14) M or 80 molecules for sulforhodamine 101 and 1.5 x 10(-13) M or 220 molecules for fluorescein in a 50 micron i.d. capillary. An electropherogram of a mixture of amino acids derivatized with both Bodipy 503/512 C3 and Bodipy 576/589 C3 demonstrates that the analytes can be differentiated on the basis of both emission characteristics and migration times. With the use of organic modifiers and other complex separation media, the spectral background increases as discrete spectral features appear; the wavelength-resolved backgrounds of a variety of common CE separation conditions are presented. PMID- 7864387 TI - Dynamics surrounding Cys-34 in native, chemically denatured, and silica-adsorbed bovine serum albumin. AB - We report the steady-state and time-resolved fluorescence of 6 acryloyl(dimethylamino)naphthalene (acrylodan) covalently attached to Cys-34 in bovine serum albumin (BSA). For this conceptually simple system, complicated fluorescence intensity and anisotropy decay kinetics are observed. The steady state and time-resolved results demonstrate the presence of an excited-state reaction for the BSA-acrylodan system. Additional analysis shows that dipolar relaxation of the environment surrounding acrylodan within BSA is responsible for most of the observed time-dependent evolution of the emission spectrum. The effects of temperature, chemical denaturation, and protein adsorption to a bare silica substrate are also investigated. These results demonstrate the complexity of the changes within a protein/biorecognition element that affect the signal from a single fluorescent reporter group. PMID- 7864388 TI - Capillary zone electrophoresis study of naphthylethylcarbamoylated beta cyclodextrins. AB - Regiospecifically monosubstituted 1-(1-naphthyl)ethylcarbamoylated beta cyclodextrins (NEC-beta-CDs) were successfully employed as chiral additives in capillary zone electrophoresis (CZE) to achieve chiral separation of N-(3,5 dinitrobenzoyl)phenylglycine (3,5-DNB-PG), phenylalanine (3,5-DNB-PA), and homophenylalanine (3,5-DNB-HPA). The enantioselectivity of the various site substituted NEC-beta-CDs in CZE was compared with that of native beta-CD. Complexation constants of the three 3,5-DNB amino acids with beta-CD were determined from the CZE results: 3,5-DNB-L-HPA, 473 +/- 9 M-1; 3,5-DNB-D-HPA, 460 +/- 10 M-1; 3,5-DNB-L-PA, 260 +/- 4 M-1; 3,5-DNB-D-PA, 161 +/- 3 M-1; and 3,5-DNB D, L-PG, 43 +/- 4 M-1. PMID- 7864389 TI - Artificial blood. PMID- 7864390 TI - Species dependency of the liquid chromatographic properties of silica-immobilized serum albumins. AB - A series of chemically bonded serum albumins from different animal sources (i.e., bovine, human, sheep, and pig) have been prepared via a three-step procedure. Subsequently, the differences in the amino acid residues forming the binding pockets for L-tryptophan and related analogues (subdomain IIIA) were investigated using liquid chromatography. Even though there is a high homology among the different species of serum albumins obtained from a number of animal sources, single changes in the relevant sequence were found to significantly alter the proteins' binding selectivity. Van't Hoff plots for both the L- and the D enantiomers show expected properties. However, changes in the amino acid sequence are reflected in changes of the specific binding/chromatographic selectivity for differently substituted L-tryptophans. PMID- 7864391 TI - Bioavailability estimation by reversed-phase liquid chromatography: high bonding density C-18 phases for modeling biopartitioning processes. AB - There have been many attempts to estimate biological activity with either 1 octanol/water partition coefficients or chromatographic retention parameters. Bulk phases may not be appropriate, however, for modeling a partitioning process in an interphase such as biological membranes. Chromatographic stationary phases can be argued as having structure similar to a membrane because of chain organization; however, the density of the grafted stationary-phase chains in commercially available stationary phases is much too low to provide a suitable model. We have previously developed a new scheme for derivatizing silica surfaces that produces stationary phases of significantly higher chain density than traditional methods. Investigation of the molecular mechanism and thermodynamics of solute partitioning into the different phases has shown that densely bonded reversed-phase stationary phases mimic partitioning to a biomembrane better than does bulk-phase octanol. Here we report chromatographic retention for pesticides, PAHs, and barbiturates using a C-18 column with high alkyl chain density, and in all cases, correlations of log k'w with bioavailability are equivalent to or better than correlations of bioavailability with the octanol/water partition coefficient. PMID- 7864392 TI - Analysis of single cells by capillary electrophoresis with on-column derivatization and laser-induced fluorescence detection. AB - On-column derivatization of single mammalian cells with capillary electrophoretic separation and laser-induced fluorescence detection is described. Individual cells are electrophorectically injected into the front end of the separation capillary, which is used as a chamber to lyse the cell and derivatize its contents for subsequent separation and detection. Reagents to lyse the cell and derivatize its contents are electrophoretically injected into the front end of the capillary (2.7 mm, 600-pL volume for a 17-microns-i.d. capillary) after the cell has been injected. Dopamine and five amino acids have been quantitatively determined in individual rat pheochromocytoma cells after on-column derivatization with naphthalene-2,3-dicarboxaldehyde and CN-. Average values of compounds determined in these cells range from 180 +/- 110 amol/cell for aspartic acid to 5.1 +/- 1.5 fmol/cell for taurine. PMID- 7864393 TI - Renal anatomy of the pigmy hippopotamus (Choeropsis liberiensis): an overview. AB - The adult kidney of Choeropsis liberiensis is 74.8% cortex and 22.9% medulla. The neonatal cortex is relatively less. A single kidney has about 3 x 10(6) glomeruli. These form 5% of renal mass in the adult but more so in neonates. The primary tubus maximus, TM1, follows the lateral curvature of the kidney. It gives off, toward the hilum, dorso-ventrally paired secondary tubi maximi, TM2. The tubi are a single layer of high cuboidal epithelium from which terminal collecting ducts arise throughout the surrounding inner medulla. The cranial and caudal limbs of TM1 open at a diminutive pelvis which receives a small papilla in continuity with TM1. The medulla is continuous although variably distorted by folds of cortex at the lateral curvature of the kidney. The renal lobes project toward the medial border and consist of cortex, medulla and TM2. The lobar cortex is continuous with the common cortex of the lateral curvature. The kidney, although strongly lobed, has no infundibula or rencules. A main peripheral vein courses medial and parallel to TM1. It is apparently a modified large arcuate vein and receives arcuate and interlobar tributaries. At the level of the papilla it joins the main renal vein. The arterial supply is mainly by interlobar arteries but there are also sizeable external perforator arteries which branch from the main renal artery and perforate the cortex of lobes about the hilum. The source of the arteries is illustrated. PMID- 7864394 TI - The anatomy of the male genital system of the beluga whale, Delphinapterus leucas, with special reference to the penis. AB - The genital organs of four male adult beluga whales and one newborn animal were dissected and the main characteristics are described. As in other species of cetaceans, the testes and the greatest part of the penis are located inside the abdominal cavity. The penis has a sigmoid flexure and belongs to the fibroelastic type with a thick tunica albuginea and a small amount of vascular spaces in the erectile tissue. The prostate gland, found in other cetaceans, was not seen macroscopically, but only small prostate rudiments could be identified histologically. The os penis and the other accessory glands are absent as in other whales. PMID- 7864395 TI - Ductus epididymidis compartments and morphology of epididymal spermatozoa in llamas. AB - In this work, an attempt was made to asses possible regional specializations in the llama ductus epididymidis. According to histological and histochemical criteria, six segments (I-VI) were identified. Segment I was a short region where ductuli efferentes joined the ductus epididymidis. Segments II and III showed maximal epithelial height and mitotic activity, respectively, and weak LDH activity. Epithelial cells in segment IV contained PAS-positive, amylase and neuraminidase-resistant secretory granules. Segment V showed strong acid phosphatase and lactate dehydrogenase activities. Segment VI was characterized by moderate acid phosphatase and high lactate dehydrogenase activities, respectively, and by maximal spermatozoa packaging. Scanning electron microscopy of epididymal spermatozoa revealed that cytoplasmic droplet translocation was accomplished at the distal part of the corpus epididymidis. Bent middle pieces characterized spermatozoa during droplet translocation. PMID- 7864396 TI - Fiber types distribution in the digastric muscle of tufted capuchin monkey (Cebus apella). AB - Fiber types distribution in the digastric muscle of tufted capuchin monkey was studied by means of NADH-TR, myosin-ATPase, after alkaline and acid preincubations and SDH histochemical reactions. Three different types of fibers were found presenting an equal distribution. The percentage and types of fibers were as follow: 18.2% SO (Slow Oxidative), 38.4% FOG (Fast Oxidative Glycolytic) and 43.4% FG (Fast Glycolytic). FG fibers revealed the largest area. The relatively high concentration of fast twitch (81.2%) seems to indicate this muscle is involved with the acceleration and fast speed of jaw movements. Aerobic metabolism represented by SO + FOG fibers (56.6%) suggests that this muscle possesses an additional role than that related to the lowering of the jaw. PMID- 7864397 TI - Heterogeneity of pericyte populations in equine skeletal muscle and dermal microvessels: a quantitative study. AB - The objective of this ultrastructural investigation was to determine if populations of pericytes in equine dermal and skeletal muscle capillaries increase in a head-to-foot direction, as has been reported in human skeletal muscles. Samples of equine microvessels were obtained from the longissimus dorsi skeletal muscle 150 cm. from the ground, from the dermis above this muscle, from the extensor carpi radiali muscle at 55 cm. from the ground, from the dermis adjacent to that muscle, and from dermis 15 cm. from the ground, just above the hoof wall. Tissues were processed for transmission electron microscopy. Electron micrographs were analyzed with a digitizing tablet and computer, to determine the ratios of endothelial cell outer circumference and pericyte inner lengths. Pericytes were separated into two classes; those closest to the endothelial cells were defined as covering capillaries. Those separated from endothelial cells by another layer of pericytes were termed enveloping pericytes. There was much greater coverage and envelopment of dermal capillaries (85% and 135%) than skeletal muscle capillaries (27% and 31%). Regression analysis of the pericyte coverage and envelopment of dermal capillaries revealed a significant increase in pericytes toward the ground. Similarly, the two skeletal muscle tissues differed significantly in their pericyte coverage and envelopment (25/27% at 150 cm., 31/35 at 55 cm.). The data indicate that, as in humans, capillary pericytes are not homogeneously distributed within the same tissues, but are more numerous closer to the ground. Differences in pericyte populations could affect studies of microvessel function. PMID- 7864398 TI - The anatomic features of the normal tarsus of the live horse as perceived by the sense of sight. AB - A description is given of 75 features present in the normal tarsus of the standing horse which are apparent due to visible skin contours overlying them. Depending on whether or not the pelvic limb is supporting full weight or resting, some contours alter their configuration. Therefore the contour of each underlying feature is described separately for each stance of the limb. It is considered that visual inspection and identification of the apparent superficial features of the normal equine tarsus form the basis of orientation and clinical inspection. Furthermore, these features provide reference points for procedures associated with surgery, arthroscopy, intraarticular treatment and anesthesia of a horse's tarsus suspected of being injured or infected. PMID- 7864399 TI - Analysis of the pituitary-thyroid axis in bilaterally adrenalectomized or adrenal transplanted rats. AB - The percentage, distribution, shape, intensity of staining and morphometrical parameters of the pituitary TSH immunoreactive cells and the histological features of the thyroid glands, were compared between adult rats with intact adrenals, without adrenals and biadrenalectomized animals with neonatal adrenal grafts. After the removal of the adrenal glands, TSH immunoreactive cells increased in percentage and exhibited a higher complexity of the cellular outline, than that of the intact animals. The nuclear, cytoplasmic and cell areas were significantly increased. However the bigger enhancement of the cytoplasmic area relative to the nuclear area, produced a decrease in the nuclear/cell area ratio. The thyroid glands showed some histological evidences of activation. After the transplantation of neonatal adrenal glands to adult rats, several adrenocortical nodules were present in the lumen of the small bowel segment. These adrenal masses induced a great decrease in the TSH cell area, which coupled with a smaller but significant variation of the nuclear area, led to an increase in the nuclear/cell area ratio relative to that observed in adrenalectomized animals. In addition, the distribution, shape and intensity of the immunoreactive material was similar to that observed in intact animals. In this experimental group, thyroid histology was observed to be similar to that of the intact animals. PMID- 7864400 TI - The poll glands of the dromedary (Camelus dromedarius): ultrastructural characteristics. AB - The poll glands of the camel are tubuloalveolar glands. They consist of lobules separated by interlobular connective tissue. Adrenergic axons and blood vessels including fenestrated capillaries are present in the intralobular connective tissue in close proximity to the secretory cells. The prominent features of the secretory cell cytoplasm are many mitochondria, smooth endoplasmic reticulum, and many vesicles in various secretory stages. It is concluded that the secretory cells have apocrine as well as merocrine modes of secretion. The glands may have the ability to uptake hormones and concentrate them. Additional work is needed before considering these glands as steroid-secreting glands. PMID- 7864401 TI - Two-headed, two-necked conjoined twin calf with Arnold-Chiari malformation in a Japanese shorthorn calf. AB - A dicephalic Arnold-Chiari malformation (ACM) case revealed asymmetrical cranial bone abnormalities: the right cranium had the typical findings associated with bovine monocephalic ACM cases, whereas the left cranium had malformation that has not yet been described in previous bovine ACM cases. The only common finding in each cranium was a relative smallness of the cranium as the encasement of the brain. PMID- 7864402 TI - Retinal photoreceptor fine structure in the great blue heron (Ardea herodias). AB - The morphology of the retinal photoreceptors of the great blue heron (Ardea herodias) has been investigated by light and electron microscopy. They consist of rods, single cones and double (unequal) cones present in a ratio of about 2:1:1 respectively. The rods are slender elongated cells with outer segments that reach to the retinal epithelial (RPE) cells and are surrounded by pigment-rich apical processes of the RPE cells in the light-adapted state. The rod inner segment displays an ellipsoid of mitochondria, an hyperboloid of glycogen, much rough ER, numerous polysomes, Golgi zones and autophagic vacuoles. The rod nucleus is located deep in the outer nuclear layer and the rod synaptic pedicle displays both invaginated and superficial synaptic sites. Single cones display a slightly tapered outer segment, a large electron lucent oil droplet and an ellipsoid of mitochondria in the apex of the inner segment. Double cones consist of a long thin chief member which shows an electron dense oil droplet and a shorter, stouter accessory cone with no oil droplet but a paraboloid of glycogen below the ellipsoid. As in the single cone, polysomes, RER and Golgi zones are present in the myoid region of both members of the double cone. All photoreceptor types have a connecting cilium joining inner and outer segments. Near the external limiting membrane, the chief and accessory cones show intercellular junctions. All cone photoreceptors are relatively small in diameter and hence tightly packed. While rods are felt to undergo retinomotor movements, cones are felt to move minimally or not at all. Both single and double cones display several invaginated (ribbon) synapses as well as numerous superficial (conventional) synaptic sites. PMID- 7864403 TI - Retinal pigment epithelial fine structure in the great blue heron (Ardea herodias). AB - The fine structure of the retinal epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) has been studied by light and electron microscopy in the great blue heron (Ardea herodias). In this species the RPE consists of a single layer of cuboidal cells which display numerous basal (scleral) infoldings and plentiful apical (vitreal) processes which surround photoreceptor outer segments. These epithelial cells are joined laterally by a series of tight junctions located in the mid to basal region. Within the epithelial cells, smooth endoplasmic reticulum is very abundant while rough ER is not. Mitochondria (some of which are ring-shaped) and polysomes are abundant. In light-adaptation the RPE nuclei are large vesicular and basally located while the melanosomes of these cells are almost exclusively located within the apical processes. Myeloid bodies are large and numerous and often show ribosomes on their outer surface. Bruch's membrane (complexus basalis) shows the typical pentalaminate structure noted in the majority of vertebrates except teleosts. The choriocapillary endothelium is very thin facing Bruch's membrane but is only moderately fenestrated. The majority of these fenestrations show a single-layered diaphragm but double layered diaphragms are also noted. PMID- 7864404 TI - Effects of intrathecal mu, delta, and kappa agonists on thermally evoked cardiovascular and nociceptive reflexes in halothane-anesthetized rats. AB - Despite significant opioid binding in the intermediolateral cell column, the effects of intrathecal injections of mu, delta, and kappa opioid agonists on the cardiovascular response to noxious stimulation have not been examined systematically. The pharmacology of intrathecally administered opioid agonists (mu, morphine, [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAGO); delta, metkephamid, [D Ala2-D-Leu5]enkephalin (DADL), [D-Pen2,D-Pen5]enkephalin (DPDPE); kappa, U50488H and PD117,302) or agonist-antagonist (nalbuphine) on somatomotor (tail-flick) and cardiovascular changes (blood pressure and heart rate) evoked by immersing the tail in 53 degrees C water were examined in rats anesthetized with halothane (0.75%) and in which intrathecal catheters had been chronically implanted. Intrathecal administration of mu and delta, but not kappa agonists or agonist antagonist produced a dose-dependent block of tail-flick and evoked cardiovascular responses with the order of activity being as follows: DAGO > metkephamid DADL > morphine > DPDPE >> nalbuphine = PD117,302 = U50488H = 0. These effects were reversed readily by the opioid antagonist naloxone. In addition, intrathecal administration of mu and delta but not kappa or agonist antagonist had little effect on resting heart rate and blood pressure. These data indicate that the agonist occupancy of spinal mu and delta, but not kappa agonists can profoundly modulate the autonomic and somatomotor response evoked by high threshold thermal stimuli. PMID- 7864405 TI - Effects of verapamil on spinal anesthesia with local anesthetics. AB - The primary mode of action of local anesthetics is through sodium channel and axonal conduction blockade. Local anesthetics also have extensive effects on presynaptic calcium channels that must function to stimulate the release of neurotransmitters. Thus, interference with calcium channel conductance may enhance spinal anesthesia with local anesthetics. The present study was designed to investigate the effects of the intrathecal calcium channel blocker, verapamil, on the spinal anesthesia from lidocaine and tetracaine. Male Sprague-Dawley rats were chronically implanted with lumbar intrathecal catheters. Tail-flick (TF) and mechanical paw pressure (MPP) tests were used to assess thermal and mechanical nociceptive threshold, respectively. Motor function was assessed using a modified Langerman's scale. Intrathecal lidocaine or tetracaine alone showed the prolongation of TF latency, the increase of MPP threshold, and the increase in motor function scale in a time- and dose-dependent manner. Although intrathecal verapamil alone demonstrated neither sensory nor motor block at the doses used (50-200 micrograms), the combination of lidocaine (20, 50, 100, or 200 micrograms) or tetracaine (10, 20, 50, or 100 micrograms) and verapamil (50 micrograms) produced the more potent and prolonged antinociception and motor block when compared with local anesthetics alone. We interpreted these results to indicate that the intrathecal calcium channel blocker, verapamil, potentiates spinal anesthesia with local anesthetics. PMID- 7864406 TI - Effects of anesthesia and surgery on plasma endothelin levels. AB - To investigate the clinical significance of endothelin (ET), a potent and long acting vasoconstrictor peptide in anesthesia and surgery, we measured plasma ET like immunoreactivity (ET-LI) levels by using radioimmunoassay in patients undergoing various kinds of surgery under general anesthesia. No significant changes in plasma ET-LI levels were observed in patients undergoing relatively minor surgery under general anesthesia with nitrous oxide and halothane (n = 6), enflurane (n = 6), or isoflurane (n = 5). Although plasma ET-LI levels after surgery in patients undergoing total knee replacement (12.4 +/- 0.9 [mean +/- SEM] pg/mL, n = 7), hysterectomy (11.4 +/- 0.6 pg/mL, n = 8) or cholecystectomy (14.8 +/- 1.2 pg/mL, n = 9) were no different from those before surgery, plasma ET-LI levels after surgery in patients undergoing gastrectomy (20.4 +/- 1.9 pg/mL, n = 15), esophagectomy (24.7 +/- 2.5 pg/mL, n = 12), hepatectomy (27.5 +/- 3.4 pg/mL, n = 12), or heart surgery (43.1 +/- 4.1 pg/mL, n = 18) were higher than those before surgery (P < 0.05). Changes in plasma ET-LI levels during surgery had positive correlations with the duration of the operation (n = 100, r = 0.51, P < 0.01) and intraoperative blood loss (n = 100, r = 0.30, P < 0.01). In patients undergoing subtotal esophagectomy, the plasma ET-LI level did not increase during the initial 2 h, but increased gradually during surgery, reached a peak within a few hours after surgery, and declined slowly thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864407 TI - Who uses transesophageal echocardiography in the operating room? AB - A survey was made of 155 anesthesiology residency programs in the United States to determine the patterns of use, responsibility for interpretation, and training of those responsible for intraoperative transesophageal echocardiography (TEE). Survey questions included numbers and types of cases for which TEE is used, who interprets TEE data and how they are trained, the extent of resident training in TEE, and beliefs about the utility of TEE. One hundred eight completed surveys were returned (70% response). Of those responding, 98 (91%) use intraoperative TEE. In 53 of those 98 institutions (54%), an anesthesiologist was primarily responsible for the interpretation of TEE data, whereas a cardiologist was responsible in the remainder. Approximately 35% of anesthesiologists using TEE had training in its use during residency or fellowship; the remainder were trained after finishing residency or fellowship. Forty-two percent of anesthesiologists who use TEE leave a formal interpretation on the chart apart from the anesthesia record, and 43% bill specifically for performing TEE. Although 69% of those responding thought that formal credentials should be required for anesthesiologists to use intraoperative TEE, only 32% reported that their institutions actually mandated this. 38% of those responding stated that they offer a dedicated TEE rotation to their residents, and 13% thought that their graduating residents were trained well enough to use TEE on their own. Among academic institutions responding, the use of intraoperative TEE is nearly universal, responsibility for its interpretation is split almost evenly between cardiologists and anesthesiologists, and there is a disparity between opinions and reality with regard to TEE credentialing for anesthesiologists. PMID- 7864408 TI - Reductions in platelet force development by cardiopulmonary bypass are associated with hemorrhage. AB - Quantitative assessment of platelet dysfunction after cardiopulmonary bypass (CPB) and prediction of excessive microvascular bleeding remain elusive goals. We used a sensitive instrument capable of simultaneously measuring the force generated by platelets during plasma clot retraction and global clot strength. We hypothesized that CPB would significantly reduce these two variables. Platelet rich plasma was obtained from eight patients undergoing aortocoronary revascularization prior to induction, after 90 min of CPB, and after protamine administration. Platelet force development was measured using a standardized technique that controlled for platelet number and permitted clot formation in the presence of heparin. Despite the presence of a measurable elastic modulus, platelet force development during bypass was abolished. Peak platelet force development after CPB was significantly lower than before CPB (5255 +/- 955 dynes vs 11,600 +/- 780 dynes, P = 0.01). The percent recovery (after/before bypass) of peak platelet force development inversely correlated with tube thoracostomy drainage during the first 24 h after placement (rs = -0.71, P = 0.048). This study demonstrates that CPB has dramatic effects on platelet force development. The correlation between the percent recovery of peak platelet force development and blood loss supports the clinical relevance of this measurement. PMID- 7864409 TI - Mixed venous oxygen saturation during cardiopulmonary bypass poorly predicts regional venous saturation. AB - Mixed venous oxygen saturation is generally accepted as an indicator of adequacy of systemic oxygen delivery; however, cardiopulmonary bypass (CPB) may alter this relationship. Major postoperative complications potentially secondary to inadequate oxygen delivery during CPB indicate that mixed venous oxygen saturation may not detect regional venous desaturation during CPB. We therefore tested the hypothesis that mixed venous oxygen saturation and pH did not predict regional venous oxygen saturations and pH during 2 h of bypass in a swine model. Six immature swine (27-34 kg) received standard normothermic CPB. Sagittal sinus and portal vein oxygen saturations and blood gases were measured at 30, 60, 90, and 120 min of bypass. Although the venous reservoir oxygen saturation remained unchanged during 2 h of bypass, sagittal sinus saturation and pH decreased significantly (66% +/- 3.3% to 33% +/- 2.2% and 7.38 +/- 0.04 to 7.23 +/- 0.05, respectively). Likewise in the portal vein, oxygen saturation and pH also decreased (82% +/- 2.4% to 59.3% +/- 3.9% and 7.39 +/- 0.03 to 7.27 +/- 0.06, respectively). We conclude that profound regional venous desaturation and progressive regional acidemia may go undetected even when a standard pump flow rate of 100 mL.kg-1.min-1 is used and mixed venous oxygen saturation is normal. PMID- 7864410 TI - Angiotensin-converting enzyme inhibitors increase vasoconstrictor requirements after cardiopulmonary bypass. AB - Preoperative use of angiotensin-converting enzyme (ACE) inhibitors is common and has been associated with hypotension at separation from cardiopulmonary bypass (CPB). This study prospectively examined the influence of chronic preoperative ACE inhibitor use and other perioperative factors on the incidence of vasoconstrictor therapy required to maintain systolic blood pressure at more than 85 mm Hg despite a normal cardiac output after CPB in 4301 adults undergoing elective coronary artery and/or valve surgery. Hypothermic, nonpulsatile CPB and either opioid or ketamine-benzodiazepine anesthesia were common features of the operations. At least two vasoconstrictor infusions (phenylephrine, norepinephrine, or dopamine) were required for low perfusion pressure despite adequate cardiac output after CPB in 7.7% of 519 ACE-inhibited patients and 4.0% of 3782 patients not receiving ACE inhibitors (P = 0.0001). In the first 4 h after arrival in the intensive care unit, the need for vasoconstrictor infusions to treat hypotension with adequate cardiac output did not differ, although more ACE-inhibited patients (6.4%) exhibited low values of systemic vascular resistance (< 600 dyne.s.cm-5) than patients not receiving ACE inhibitors (2.8%; P = 0.0002). Logistic regression analysis identified preoperative ACE inhibitor use, congestive heart failure, poor left ventricular function, duration of CPB, reoperative surgery, age, and opioid anesthesia as independent risk factors for requiring > or = 2 vasoconstrictor infusions after CPB. No other preoperative drug therapy significantly altered this outcome. PMID- 7864411 TI - Influence of intravenous administration of angiotensin-converting enzyme inhibitor enalaprilat on cardiovascular mediators in cardiac surgery patients. AB - The renin-angiotensin system (RAS) is important in controlling and maintaining cardiovascular homeostasis. In a randomized, prospective study, the response to intravenous (i.v.) administration of the angiotensin-converting enzyme (ACE) inhibitor enalaprilat (0.06 mg/kg) on important controllers of the circulation was investigated in 14 patients undergoing aortocoronary bypass grafting with a mean arterial blood pressure (MAP) > 85 mm Hg after induction of anesthesia. Fourteen patients received saline solution as placebo (control group). Endothelin (ET), atrial natriuretic peptide (ANP), catecholamine (epinephrine, norepinephrine) plasma levels, and ACE activity were measured from arterial blood sampled before injection of enalaprilat or NaCl solution (baseline values), 10 min and 30 min thereafter, immediately before the start of cardiopulmonary bypass (CPB), immediately after CPB, and at the end of surgery. MAP, heart rate (HR), cardiac index (CI), and systemic vascular resistance (SVR) were also monitored. ACE activity was similar at baseline in both groups; after i.v. injection of enalaprilat, it significantly decreased (from 35.1 +/- 11 to 4.4 +/- 1.0 U.min 1.L-1 30 min after injection) and remained reduced until the end of the operation (295 +/- 31 min after injection). ANP plasma levels were increased beyond normal (> 100 pg/mL) at baseline in both groups. They increased significantly in the control patients, but remained almost unchanged in the enalaprilat-treated patients within the entire study period. Plasma concentration of ET also increased only in the control group and was increased after CPB (8.6 +/- 1.2 pg/mL at the end of the operation).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864412 TI - Influence of jet direction on pulmonary vein flow patterns in severe mitral regurgitation. AB - Pulmonary vein flow patterns measured with transesophageal echocardiography have been used recently to assess the severity of mitral valve regurgitation. This study was designed to determine whether regurgitant jet direction selectively influences the pattern of flow in right and left pulmonary veins. Thirty-seven patients undergoing mitral valve repair or replacement for severe valvular regurgitation were studied intraoperatively with biplane transesophageal echocardiography. Regurgitant jets were classified by color flow mapping as central or wall, with the latter further classified as septal, lateral, anterior, or posterior in the two orthogonal scan planes. Pulmonary vein flow patterns were measured with pulsed wave Doppler ultrasonography and categorized as showing normal, blunted, or reversed systolic flow. Right and left pulmonary vein flow patterns were identical in the majority of patients studied (78%). Eight patients had discordant flow patterns. In seven of eight patients, the more abnormal pattern was seen in the right pulmonary vein, despite the fact that the regurgitant jets were directed centrally in four of these seven patients. Since discordant pulmonary vein flow patterns occurred in 5 of 15 patients (33%) with central jets, but in only 3 of 22 patients (14%) with eccentric wall jets, it is unlikely that mitral regurgitation jet direction per se causes predictable and selective unilateral alteration in pulmonary vein flow patterns. PMID- 7864413 TI - Hemodilution impairs hypocapnia-induced vasoconstrictor responses in the brain and spinal cord in dogs. AB - Despite the increasing use of plasma expanders in the perioperative period, there have been few studies of cerebrovascular responsiveness during hemodilution. The present study was performed to evaluate the influence of isovolemic hemodilution on vasoconstrictor responses in the brain and spinal cord during hypocapnia. Sixteen mechanically ventilated, halothane-anesthetized dogs were randomly divided into two equal groups: Group 1, control group (hematocrit [Hct], 42% +/- 2%); Group 2, isovolemic hemodilution with 5% dextran 40 (Hct, 19% +/- 2%). Hypocapnia (22 +/- 1 mm Hg) was induced in both groups by removal of dead space tubing without altering mechanical ventilation. Regional blood flow in the brain and spinal cord was measured with 15-microns radioactive microspheres and used to calculate regional vascular resistance (RVR). In Group 1, hypocapnia caused increases in RVR (ranging from 44% +/- 10% in the cerebral cortex to 93% +/- 17% in the thoracic spinal cord). In Group 2, hemodilution itself decreased RVR relatively uniformly throughout the brain and spinal cord. After hemodilution, hypocapnia had no significant effect on RVR in the cerebral cortex, cerebellum, pons, and medulla, and caused less pronounced increases in RVR within the spinal cord. We conclude that hemodilution either attenuated or completely abolished vasoconstrictor responses within the brain and spinal cord during hypocapnia. Furthermore, the present findings suggest that induced hypocapnia may be less effective as a clinical maneuver to reduce increased intracranial pressure during hemodilution. PMID- 7864414 TI - Anesthesia with increasing doses of sufentanil and midlatency auditory evoked potentials in humans. AB - Our interest focused on the question whether sufentanil differs from alfentanil, fentanyl, and morphine with regard on its effects on midlatency auditory evoked potentials (MLAEP). Therefore, we studied MLAEP during general anesthesia with increasing doses of sufentanil in 16 patients scheduled for elective major urologic surgery. Anesthesia was induced with sufentanil (1 microgram/kg every 7 min to a total dose of 3 micrograms/kg). In 8 of 16 patients, further incremental doses of sufentanil were given to a total dose of 5 micrograms/kg. Auditory evoked potentials were recorded before and 5 min after every sufentanil dose on vertex (positive) and mastoids on both sides (negative). Latencies of the peaks V, Na, Pa, Nb, and P1 (ms), and amplitudes Na/Pa, Pa/Nb, and Nb/P1 (microV) were measured. In the awake state, MLAEP had high peak-to-peak amplitudes and a periodic waveform. During general anesthesia the brainstem response V was stable to increasing doses of sufentanil. There was a marked statistically significant increase in latency and decrease in amplitude of Nb and P1 after 1-2 micrograms/kg sufentanil, which remained stable under further sufentanil application. In contrast, the early cortical potentials Na and Pa increased only slightly in latencies. This increase was statistically significant at 4 micrograms/kg for Na and at 3 and 4 micrograms/kg for Pa. For the amplitudes Na/Pa and Pa/Nb there was only a slight and statistically insignificant reduction. After the largest dose of sufentanil (3-5 micrograms/kg) Na and Pa showed a similar pattern as in awake patients. We conclude that sufentanil does not differ essentially from alfentanil, fentanyl, and morphine with regard on its effects on MLAEP. PMID- 7864415 TI - Cardiorespiratory effects of premedication for children. AB - Cardiovascular and respiratory effects of pediatric preanesthetic premedication have received only minimal attention, probably because most children tolerate such drugs without apparent ill effect. In children with congenital heart disease or other serious illness, there is often reluctance to use premedication. We sought to determine whether different premedication regimens produced significant cardiorespiratory effect. A randomized prospective study of the cardiovascular and respiratory effects of different oral, nasal, and rectal premedication regimens was conducted. Fifty-eight young children (average age 2.7 yr) were studied. Oral meperidine (3 mg/kg) with pentobarbital (4 mg/kg) decreased heart rate, mean arterial pressure, cardiac index, respiratory rate, and oxygen saturation. Stroke volume was maintained. Nasal ketamine (5 mg/kg) with midazolam (0.2 mg/kg) produced no significant cardiovascular or respiratory effects. Rectal methohexital (30 mg/kg) increased heart rate with a coincident decrease in stroke volume but had no other positive or negative cardiac or respiratory effect. This information documents disparate cardiorespiratory effects of different preanesthetic medications in normal children. PMID- 7864416 TI - Postoperative analgesia after lumbar laminectomy: epidural fentanyl infusion versus patient-controlled intravenous morphine. AB - We compared the efficacy and safety of continuous epidural fentanyl infusion with intravenous morphine via a patient-controlled analgesia system (IV-PCA) in the management of postoperative pain after lumbar laminectomy. Twenty patients undergoing elective lumbar laminectomy were randomly allocated to one of two groups. The epidural group (n = 10) received an epidural fentanyl infusion (2 micrograms/mL at 4-10 mL/h) while the IV-PCA group (n = 10) received IV morphine through a PCA system. The general anesthetic technique was standardized. Visual analog pain scores were recorded at 12, 24, and 48 h after the operation. The amount of morphine (or its equivalent in fentanyl) used over the 48-h postoperative period was documented. The postoperative pain scores were significantly lower in the epidural group than in the IV-PCA group throughout the study period. The total consumption of morphine (or its fentanyl equivalent) over the 48-h period was significantly lower (P < 0.001) in the epidural group compared to the IV-PCA group. Although more patients in the IV-PCA group required urinary catheterization and had somnolence than the epidural group, there was no difference in the incidence of vomiting or pruritus. No patient developed respiratory depression or wound infection. We conclude that continuous epidural infusion of fentanyl is superior to IV-PCA morphine in the management of pain after lumbar laminectomy. PMID- 7864417 TI - OP-1206, a prostaglandin E1 derivative, attenuates the thermal hyperesthesia induced by constriction injury to the sciatic nerve in the rat. AB - Nerve ischemia induces wallerian degeneration and peripheral neuropathy, the nerve constriction injury induces thermal hyperesthesia. Nerve ischemia is one possible mechanism in the development of thermal hyperesthesia in the nerve constriction injury model. Prostaglandin E1 increases tissue blood flow. In the present study, the authors examine the role of nerve ischemia in the maintenance of the thermal hyperesthesia induced by nerve constriction injury by orally administering OP-1206, a prostaglandin E1 derivative. A nerve constriction injury model was created by making four loose ligations around the rat sciatic nerve, which induces thermal hyperesthesia in the ligated paw in 2-5 days. OP-1206, was administered six times (Day 7, one time; Day 8, two times; Day 9, two times; Day 10, one time). A single administration of OP-1206 had no effect on the thermal hyperesthesia. Six hours after the sixth-administration of OP-1206, the level of the thermal hyperesthesia was attenuated in a dose-dependent manner, and this effect lasted more than 1 day after the last drug administration. These data indicate that nerve ischemia plays an important role in maintaining the thermal hyperesthesia induced by nerve constriction injury in the rat. PMID- 7864418 TI - A dose-response study of the effects of intravenous midazolam on cold pressor induced pain. AB - The effects of intravenous midazolam (0.75, 1.5, and 3 mg/70 kg) were examined and compared to that of fentanyl (0.1 mg/70 kg; positive control) and saline on pain induced by a cold pressor test. Both sensory and affective components of the pain response were assessed, as there is some evidence that benzodiazepines reduce the affective component. Healthy volunteers (three females, nine males) were enrolled in a prospective, double-blind, randomized, cross-over trial in which mood and psychomotor performance were also examined. Five minutes and 135 min postinjection, subjects immersed their forearm in ice-cold water for 3 min while assessments of pain were recorded. During the first immersion, subjects reported significantly lower pain intensity and bothersomeness ratings after having been injected with fentanyl, relative to the saline and midazolam conditions, which did not differ significantly from each other. Fentanyl and midazolam had prototypical mood altering and psychomotor impairing effects. We conclude that midazolam in our laboratory setting at the doses and route of administration studied had no effects on either the sensory or affective components of the pain experience. PMID- 7864419 TI - Duration of vecuronium-induced neuromuscular block as a predictor of liver allograft dysfunction. AB - The major causes of liver graft failure are acute rejection, technical failure, and primary nonfunction (PNF). This study was undertaken to determine whether delayed return of neuromuscular function correlates with allograft primary dysfunction in humans given vecuronium. Twenty-two adult patients undergoing orthotopic liver transplantation were given an initial dose of vecuronium, 0.1 mg/kg intravenously (i.v.). All patients recovered from vecuronium-induced neuromuscular block prior to explantation. No additional neuromuscular blocker was given until the liver graft was implanted and reperfused. Fifteen minutes after reperfusion another 0.1 mg/kg vecuronium was given IV and recovery time from attaining complete neuromuscular block to return of the fourth twitch of a train-of-four was recorded. Patients were divided into three groups according to postoperative liver function. Group I consisted of 17 patients with immediate normal liver graft function. Group II consisted of four patients with primary dysfunction (PDF) [peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2000 U/L, prothrombin time > 16 s, and poor quality and quantity of bile within 3 days postoperatively] which eventually recovered normal function. Group III consisted of one patient with PNF (uncorrectable coagulopathy, severe metabolic acidosis, rising AST and ALT, and minimal or no bile output), whose graft never recovered. Recovery time in Groups II and III was prolonged compared to Group I (P < 0.05). Recovery time in Group III was prolonged compared to Group II (P < 0.05). A test based on these results using a recovery time of > 135 min as a predictor of PDF has a sensitivity and specificity of 80% and 76%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864420 TI - Interaction between mivacurium and succinylcholine. AB - We investigated the interaction between mivacurium and succinylcholine when mivacurium was administered during the early recovery from succinylcholine block. We studied 40 adult patients during propofol-alfentanil-N2O-O2 anesthesia. Neuromuscular function was monitored using an electromyographic method (Relaxograph, Datex, Helsinki, Finland). Patients randomly received either 1.0 mg/kg of succinyl-choline followed by 0.15 mg/kg of mivacurium when the first twitch (T1) during succinylcholine block recovered to 5%, or 0.15 mg/kg of mivacurium without succinylcholine. Serum cholinesterase activity was lower than normal range in two patients and higher than normal range in four patients, but the dibucaine number value was normal in every patient. The mean onset time (3.8 +/- 0.9 min) (mean +/- SD) or maximal neuromuscular block (96.6% +/- 7.2%) of mivacurium did not differ between the groups. The T1 recovery times of mivacurium were slightly shorter (P < 0.05) after succinylcholine administration than without it. During recovery of mivacurium block, the fade was significantly greater, i.e., the train-of-four (TOF) ratio was lower, after succinylcholine administration than without it. Recovery index (T1 25%-75%, mean 4.7 +/- 1.3 min) and the time from the administration of mivacurium to the recovery of TOF ratio 0.7 (mean 20.4 +/- 5.1 min) were not different between the groups. In conclusion, in healthy patients succinylcholine has negligible effects on a subsequent mivacurium-induced neuromuscular block. PMID- 7864421 TI - Pharmacodynamics, pharmacokinetics, and intubation conditions after priming with three different doses of vecuronium. AB - The effects of three different priming doses of vecuronium on pharmacokinetics, pharmacodynamics, and endotracheal intubation conditions were investigated. Forty two patients were studied in two parts. In each part, 21 patients were allocated into three groups (n = 7/group) receiving 10, 15, or 20 micrograms/kg vecuronium as a priming dose, followed by a 50- micrograms/kg intubating dose 6 min later. In Part I, Train-of-Four (TOF) ratios and serum concentrations after priming were measured every minute up to the sixth minute. Onset time [from injection of the intubating dose to maximum depression of the first twitch (T1)], clinical duration (T1 return from maximum block to 25% of control), and recovery index (T1 recovery from 25% to 75% of control) were calculated and serum concentrations were determined up to 6 h after injection of the intubating dose. In Part II, the intubating dose was injected 4 min after priming, onset time was determined, and intubation conditions were scored. TOF ratio was significantly lower after priming with 20 micrograms/kg at the fifth and sixth minutes (0.59 +/- 0.29 and 0.56 +/- 0.32; mean +/- 1 SD) compared with the first minute (0.95 +/- 0.1). Recovery index was significantly increased after priming with 20 micrograms/kg (13.2 +/- 6.6 min, P < 0.05) compared with 10 micrograms/kg (9.2 +/- 4.8 min) and 15 micrograms/kg (6.7 +/- 1.5 min). Between groups no differences in onset time, clinical duration, and pharmacokinetic variables were found. In Part II, onset time and intubating scores showed no significant differences between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864422 TI - Dependence of the adequacy of muscle relaxation on the degree of neuromuscular block and depth of enflurane anesthesia during abdominal surgery. AB - We studied the intensity of neuromuscular block that is adequate for surgical relaxation at different end-tidal levels of enflurane during N2O-O2-fentanyl anesthesia in 30 patients undergoing upper abdominal surgery. After induction of anesthesia with thiopental 4-6 mg/kg and vecuronium 0.07 mg/kg intravenously (i.v.), patients were randomly assigned to receive nitrous oxide-oxygen (2:1) and enflurane at 0.3% (Group I), 0.6% (Group II), or 1.2% (Group III) end-tidal level throughout anesthesia. The initial neuromuscular block was allowed to terminate and additional increments of 1 mg vecuronium were given when indicated by clinical signs or by spontaneous electromyography of neck muscles. In Group I additional vecuronium had to be given 62 times and in Groups II and III, 33, and 16 times, respectively. The mean (SD) neuromuscular block at the time of additional vecuronium was 75.9% +/- 20.7%, 62.5% +/- 20.1%, and 39.3% +/- 21.1% in Groups I to III, respectively. We conclude that there was a clear linear relationship between the end-tidal concentration of enflurane and the degree of neuromuscular block necessary to produce adequate surgical muscle relaxation (P < 0.001). PMID- 7864423 TI - Real time versus slow-motion train-of-four monitoring: a theory to explain the inaccuracy of visual assessment. AB - The present study was undertaken to determine why visual assessment of thumb adduction in response to train-of-four (TOF) stimulation of the ulnar nerve commonly overestimates the ratio that is obtained mechanographically. In patients undergoing general endotracheal anesthesia plus vecuronium for relaxation, 73 data sets were collected at different depths of neuromuscular block in response to supramaximal TOF stimulation. Each data set consisted of: (i) visual estimation of the TOF ratio by an experienced observer; (ii) mechanographic measurement of the TOF ratio with an adductor pollicis force transducer; and (iii) determination of the TOF ratio by measuring the slow-motion thumb displacement recorded on videotape. The last 23 data sets also included visual assessment and videotape recording of evoked responses at low stimulating current (30 mA). Visual inspection at 60 mA overestimated the mechanographic ratio by 0.20 units (48%). Videotape review provided a ratio that was 0.23 units (56%) greater than that determined mechanographically. However, after the first three twitches (T1-3), the thumb did not return to the same resting position as the (original) baseline prior to the first twitch. When the change in thumb position as a result of T1-3 was taken into account, the measured height of T4 was 40% less than it was when measured from the original baseline, and the T4/T1 ratio was identical to that obtained mechanographically. For the 23 data sets obtained at low current visual assessment overestimated the mechanographic value to a lesser degree than when obtained at high current. Again, correction for the T1-3 baseline shift improved the accuracy of videotape analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864424 TI - The effect of manual bulb pump infusion systems on venous luminal pressure and vein wall integrity. AB - Anecdotal case reports have suggested a risk of extravasation injury with pressurized intravenous (i.v.) infusion systems used for rapid fluid administration. This study aims to determine the risk associated with manual bulb pump i.v. infusion sets with which in-line pressures exceeding 1000 mm Hg are possible. In Part I, 34 vein segments prepared from 29 fresh cadavers, designated "thick" or "thin" on visual appraisal, were cannulated in vitro with a 16-gauge i.v. catheter. The samples were further divided into two groups, depending on whether cannulation damaged ("traumatic") or did not damage ("atraumatic") the vein wall. The veins were sealed and pressurized with saline, and the pressure recorded at which leakage occurred. In Part II, the pressure generated by use of the manual bulb pump in forearm veins cannulated with a 16-gauge catheter was measured in 20 adult patients. The measure was repeated with graded external compression to simulate venous obstruction. The mean leakage pressure for thick- and thin-walled atraumatically cannulated veins in vitro was 1433 and 838 mm Hg, respectively (P < 0.0001). After traumatic cannulation, the leakage pressure for thick- or thin-walled veins in vitro was 361 and 260 mm Hg, respectively, and significantly different from atraumatic cannulations (P < 0.001). The mean intraluminal pressure measured during clinical use of the bulb pump was 88 mm Hg (range, 36-206 mm Hg). In some patients this exceeded the pressure needed to cause leakage in traumatically cannulated veins in vitro. The luminal pressure increased in parallel with increasing external compression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864425 TI - Comparative effects of esmolol and labetalol to attenuate hyperdynamic states after electroconvulsive therapy. AB - We studied 18 patients (age range, 53-90 yr) with at least one cardiovascular risk factor who were treated with electroconvulsive therapy (ECT) and compared effects of five pretreatments: no drug; esmolol, 1.3 or 4.4 mg/kg; or labetalol, 0.13 or 0.44 mg/kg. Each patient received all five treatments, during a series of five ECT sessions. Pretreatment was administered as a bolus within 10 s of induction or anesthesia. Doses of methohexital and succinylcholine were constant for the series of treatments and the assignment to no drug or to drug and dose was determined by randomized block design. Measurements of systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) were recorded during the awake state and 1, 3, 5, and 10 min after the seizure. The deviation of ST segments from baseline was measured by an electrocardiogram (ECG) monitor equipped with ST segment analysis software. The results (mean +/- SEM) show that without pretreatment, there were significant (P < 0.05) peak increases in SBP and HR (55 +/- 5 mm Hg and 37 +/- 6 bpm, respectively), recorded 1 min after the seizure. Comparable reductions (by approximately 50%) in these peak values were achieved after esmolol (1.3 mg/kg) or labetalol (0.13 mg/kg), and cardiovascular responses were nearly eliminated after the same drugs in doses of 4.4 and 0.44 mg/kg, respectively. The deviation of ST-segment values from baseline in any lead was not measurably influenced by either antihypertensive drug. SBP values were lower after labetalol 10 min after the seizure, but not after esmolol. Asystolic time after the seizure was not significantly longer with either drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864426 TI - Morphometric influences on intraoperative core temperature changes. AB - Intraoperative core hypothermia develops in three characteristic phases: 1) core to-peripheral redistribution of body heat that is most prominent during the first hour after induction of anesthesia; 2) subsequent slow linear decrease in core temperature resulting largely from heat loss exceeding metabolic heat production; and 3) core temperature plateau resulting when thermoregulatory vasoconstriction decreases cutaneous heat loss and constrains metabolic heat to the core thermal compartment. Accordingly, we tested the hypotheses that: 1) core cooling does not depend on body fat (BF) or the ratio of weight-to-surface area (Wt/SA) during the initial redistribution phase; 2) the core cooling phase; 2) the core cooling rate is a function of the Wt/SA ratio during the second phase; and 3) the rate of core cooling during the plateau phase (after vasoconstriction) will be determined by the percentage of BF. In 40 patients undergoing elective colon surgery, the amount of redistribution hypothermia was inversely proportional to the percentage of BF (delta TC = 0.034.BF-2.2, r2 = 0.63) and the Wt/SA ratio (delta TC = 0.052.Wt/SA-3.35, r2 = 0.66). The core cooled linearly during the second phase, and the cooling rate was inversely proportional to the Wt/SA ratio (rate = 0.035.(Wt/SA)-2.2, r2 = 0.29). Thermoregulatory vasoconstriction was effective in virtually all patients independent of their morphology, and produced a four-fold reduction in the core cooling rate. These results indicate that patient morphometric characteristics substantially influence intraoperative core temperature changes, and that the effect depends on the hypothermia phase. PMID- 7864427 TI - Subanesthetic concentrations of desflurane and isoflurane suppress explicit and implicit learning. AB - The capacity of desflurane to suppress learning is unknown. We investigated whether a subanesthetic concentration of desflurane (0.6 minimum alevolar anesthetic concentration [MAC]) suppressed learning as much as the same concentration of isoflurane, and whether such suppression differed with increasing duration of anesthesia and intervening changes in anesthetic concentration. Using a cross-over-design study in 18-30 yr-old human volunteers, we supplied answers to Trivial Pursuit (Selchow & Righter Co., Bay Shore, NY) like questions at 0.6 MAC desflurane and isoflurane before and after imposing a half-hour period at 1.7 MAC of each anesthetic, and behavioral directions and a category-example task at 0.6 MAC after the period at 1.7 MAC. These volunteers had a third anesthesia in which no information was supplied (control). After anesthesia, we tested whether the provision of answers during anesthesia increased the number of correct answers to Trivial Pursuit questions. We tested for the number of correct answers for information presented before versus after the 1.7-MAC period, for increased evocation of examples of categories presented during anesthesia, and for exhibition of a behavior suggested during anesthesia. We found that 0.6 MAC of both anesthetics prevented explicit and implicit learning before and after the period at 1.7 MAC. PMID- 7864428 TI - Propofol anesthesia does not inhibit stimulation of cortisol synthesis. AB - Recent data suggest a negative effect of propofol anesthesia on cortisol secretion. The present study was designed to evaluate the effect of propofol anesthesia on the steroidogenic potential of the adrenal glands. The response of cortisol secretion to stimulation with an adrenocorticotropic hormone (ACTH) analog during intravenous anesthesia with propofol has not been reported before. The response of the secretion of cortisol, 11-deoxycortisol, and 17 alpha hydroxyprogesterone to tetracosactide stimulation was compared in patients anesthetized with propofol-nitrous oxide (n = 10) or thiopental-isoflurane nitrous oxide (n = 10) and in normal volunteers (n = 10). The response to tetracosactide was similar in all three groups. An adequate increase in cortisol plasma concentration (more than 7.25 micrograms/dL) was obtained in all subjects except one volunteer. The increase in the plasma concentration of the cortisol precursors was also similar. We were unable to detect any influence of propofol anesthesia on the synthesis of cortisol in response to tetracosactide stimulation. PMID- 7864429 TI - The effect of propofol on normal and increased pulmonary vascular resistance in isolated perfused rabbit lung. AB - The effects of propofol and its intralipid vehicle on increased and normal pulmonary vascular resistances (PVR) were studied in an in situ perfused rabbit lung model which controlled all major determinants of PVR. Propofol at both 5 and 10 micrograms/mL significantly reduced PVR increases by the thromboxane mimetic, U46619. In contrast, similar volumes of intralipid further increased PVR. Neither propofol nor intralipid had any effect on normal PVR. We conclude that propofol at 5 and 10 micrograms/mL is able to reduce increased PVR but has no effect on normal PVR. PMID- 7864430 TI - Intraoperative hemodynamic, renin, and catecholamine responses after prophylactic and intraoperative administration of intravenous enalaprilat. AB - This study was designed to evaluate effects of enalaprilat, an angiotensin converting enzyme inhibitor, on hemodynamic and hormonal responses during surgery at endotracheal intubation, incision, and limb-tourniquet inflation. Thirty patients undergoing limb procedures with general anesthesia (N2O/narcotic technique) and a pneumatic tourniquet were randomized to receive either preoperative enalaprilat (1.25 mg intravenously [i.v.] 20 min prior to induction) or intraoperative enalaprilat (0.625 mg i.v. at the onset of tourniquet associated hypertension), with appropriate placebo controls. Arterial blood pressure and heart rate increased significantly in response to intubation in the placebo group. Although there were no significant differences in catecholamine levels, plasma renin activity was significantly increased at postincision in the preoperative-enalaprilat group versus the placebo group. This suggests that activation of the renin-angiotensin system may play a key role in mediation of intraoperative hemodynamic responses to endotracheal intubation. With respect to tourniquet hypertension, preoperative or intraoperative treatment with enalaprilat reduced neither the pressor response to tourniquet inflation nor the amount of enflurane subsequently required to control arterial blood pressure. These findings suggest that this response is mediated by pain pathways, and may be treated more effectively with anesthesia/analgesia. PMID- 7864431 TI - Anesthetic considerations in porphyrias. AB - Four hereditary types of porphyria are now classified as acute porphyrias. Enzymatic defects result in accumulation of porphyrin precursors (usually ALA and PGB). The quantity of these precursors may be normal or slightly increased in latent periods but increase to toxic levels during a porphyric crisis. Iatrogenic induction of ALA synthetase by administration of certain triggers (classically barbiturates) is only one of several factors which contribute to porphyric crisis. Signs and symptoms of acute porphyric attack consist primarily of neurologic dysfunction, which occurs secondary to neurotoxicity of ALA or diminished intraneuronal heme levels. Appropriate anesthetic management of porphyria requires knowledge of the type of porphyria (acute vs non-acute), assessment of latent versus active (crisis) phase, awareness of clinical features of porphyric attack, and knowledge of safe pharmacologic intervention. PMID- 7864432 TI - Isabella Coler Herb, MD: an early leader in anesthesiology. PMID- 7864433 TI - Anesthesia-induced rigidity, unrelated to succinylcholine, associated with Smith Lemli-Opitz syndrome and malignant hyperthermia. PMID- 7864434 TI - Malignant hyperthermia during sevoflurane administration. PMID- 7864435 TI - Anesthetic implications in stiff-person syndrome. PMID- 7864436 TI - Accumulation of a right ventricular mass during shoulder hemiarthroplasty. PMID- 7864437 TI - Facial flushing and/or generalized erythema after epidural steroid injection. PMID- 7864438 TI - Proximal saphenous neuralgia after coronary artery bypass graft. PMID- 7864439 TI - Another use for the laryngeal mask airway--as a blocker during tracheoplasty. PMID- 7864440 TI - Tracheal stenosis after a brief intubation. PMID- 7864441 TI - Bronchoscopic findings of a tension pneumothorax. PMID- 7864442 TI - Perioperative torsade de pointes ventricular tachycardia induced by hypocalcemia and hypokalemia. PMID- 7864443 TI - Atropine, halothane, and pulseless electrical activity. PMID- 7864444 TI - Long-term propofol infusion for refractory postoperative nausea: a case report with quantitative propofol analysis. PMID- 7864445 TI - Influence of anthropometric variables on the spread of epidural anesthesia. PMID- 7864446 TI - Fragmentation of tube exchanger. PMID- 7864447 TI - Here we go again. PMID- 7864448 TI - Epidural phenol administration for iliopsoas hypertonicity. PMID- 7864449 TI - Cannulation of the axillary brachial sheath in children. PMID- 7864450 TI - Accuracy of references in Anesthesia & Analgesia does not improve. PMID- 7864451 TI - A method to quickly calculate mixtures for epidural infusions. PMID- 7864452 TI - Exclusion of postoperative epidural morphine analgesia in Sweden. PMID- 7864453 TI - Pulmonary edema after Nadbath and retrobulbar blocks: a possible explanation. PMID- 7864454 TI - Prolonged use of neuromuscular blockers in the intensive care unit. PMID- 7864455 TI - Reproducibility of echocardiographically determined myocardial wall thickening. PMID- 7864456 TI - Is hemodilution effective? PMID- 7864457 TI - Role of a continuous background infusion with epidural patient-controlled analgesia. PMID- 7864458 TI - Should we correct every dysfunction? PMID- 7864459 TI - Percentage swings in extraction frequencies. PMID- 7864460 TI - Author of "Thyroid administration" article responds to commentary. PMID- 7864461 TI - Forty-year review of extraction frequencies at a university orthodontic clinic. AB - In a review of consecutive charts at 5-year intervals from the orthodontic clinic at the University of North Carolina, the number of patients with extraction of all four first premolars increased from 10% in 1953 to 50% in 1963, remained at 35% to 45% until the early 1980s, then declined sharply to the 1950s level by 1993. Extraction for camouflage of Class II malocclusion (maxillary first premolars alone or maxillary first-mandibular second premolars) reached 16% in 1968, then declined, but not as dramatically, and presently is as frequent as the extraction of four first premolars. The rate of extraction of other teeth, done for a variety of individual reasons, has remained almost constant at about 15% for the past 40 years. Thus the total extraction percentage was 30% in 1953, peaked at 76% in 1968, and declined again to 28% in 1993, with almost all the change in the percentage of four first premolar extractions. The increase in first premolar extractions occurred primarily in a search for greater long-term stability; the recent decline seems due to a number of factors. Greater concern about the impact of extraction on facial esthetics, data to suggest that extraction does not guarantee stability, concern about temporomandibular dysfunction, and changes in technique all seem to have played a role. With appropriate orthodontic mechanics, many patients with Class I crowding can be treated satisfactorily with or without premolar extraction. PMID- 7864462 TI - Crowding: timing of treatment. AB - The late mixed dentition stage of development, after the eruption of the first premolars, is a favorable time to start treatment to resolve crowding. This protocol offers the clinician choices. If nonextraction treatment is preferable, arch length preservation can provide the space for alignment in approximately 75% of all patients with crowding. If extraction treatment is indicated, the first premolars are available. PMID- 7864463 TI - A longitudinal evaluation of open mouth posture and maxillary arch width in children. AB - Open mouth posture and maxillary arch width were assessed annually for 4 years in a group of children. While younger children exhibited high levels of open mouth posture, this behavior decreased significantly over time. Racial and sex differences, as well as a race-by-time interaction were also evident. The children displayed a significant increase in maxillary arch width across time with sex and racial differences in this growth pattern. Subjects were classified as exhibiting primarily open mouth or closed mouth posture. Although both groups showed increased maxillary arch widths over time, the closed mouth subjects showed significantly greater maxillary arch growth. PMID- 7864464 TI - Posttreatment changes in different facial types. AB - The purpose of this study was to describe and compare the changes occurring during and after orthodontic treatment in three facial types: short, average and long. Sixty-six subjects with Class II, Division 1 malocclusion were evaluated. All cases were treated nonextraction, using a fixed edgewise appliance and extraoral forces. The lateral cephalogram and dental casts for each patient were measured at three different stages: pretreatment, immediately after appliance removal and at least two years posttreatment. There was a wide range of individual variation in posttreatment change for the various skeletal and dental parameters measured. With few exceptions, the three facial types did not show significant differences in posttreatment change. The relative protrusion of maxillary incisor tip (U1:A-Pog) tended to increase after treatment in the long face type while it tended to decrease in the short face type. Long face females, when compared with all other groups, showed greater posttreatment incremental increase in anterior face height as well as the greatest posttreatment decrease in maxillary arch length. Males expressed greater posttreatment incremental increases in the various linear measurements of face height than females. Differences in posttreatment change for the different facial types do not require special retention consideration. PMID- 7864465 TI - Craniofacial morphology in children with Angle Class II-1 malocclusion with and without deepbite. AB - The craniofacial morphology of children with Class II-1 malocclusion with and without deepbite was studied and compared with that of a control group of children with normal occlusion. Common for the Class II-1 children was a short mandibular corpus, which was probably the main reason these children had a distal basal jaw relationship. The Class II children with deepbite differed from the control group in ways. They had: 1) a distal relationship between points A and B; 2) a distal relationship between points A and pogonion; and 3) a discrepancy in length between the corpora of the two jaws. These deviations discriminated nearly 95% correct between the deepbite group and the controls. The most characteristic deviations in the Class II children without deepbite, in relation to the controls, were: 1) a distal relationship between points A and B; 2) a small angle between the nasal plane and the anterior cranial base; and 3) a long mental process. These deviations discriminated about 95% correct between the experimental group and the controls. Many of the craniofacial differences between the Class II groups could, theoretically, be explained by the MP-SN angle being, on average, 9 degrees larger in the children without deepbite. Most typical was that this group has 1) a larger lower anterior face height, 2) larger maxillary and mandibular incisal heights, and 3) a more obvious distal relationship between points A and pogonion. In combination, these differences discriminated correctly between the Class II groups in 90% and 97% of the cases. PMID- 7864466 TI - Landmark identification error in posterior anterior cephalometrics. AB - This study was designed to quantify the intraexaminer and interexaminer reliability of 52 commonly used posterior anterior cephalometric landmarks. The horizontal and vertical identification errors were determined for a sample of 33 skulls and 25 patients. The results show that there is a considerable range in the magnitude of error with different horizontal and vertical values. Interexaminer landmark identification error was significantly larger than intraexaminer error for many landmarks. The identification error was different for the skull sample compared to the patient sample for a number of landmarks. The relevance of knowing the identification error for each landmark being considered in a particular application was discussed. PMID- 7864467 TI - Force application and decay characteristics of untreated and treated polyurethane elastomeric chains. AB - In this study the effects of prestressing, environmental acidity, oxygen content, and temperature on mechanical properties were measured for three polyurethane based orthodontic elastomeric chains. Specimens of each chain were treated for 10 and 100 days, and their mechanical properties were compared with those of the untreated specimens via stress-relaxation tests. Conditioning treatments were determined to affect the magnitude of residual load after relaxation, with the largest effect due to prestressing. Among the other variables studied, an increase in temperature of the environment appeared to significantly influence the degradation mechanism responsible for the deterioration of the mechanical properties of polyurethane elastomers (p < 0.001); acidity and oxygen content had no significant effects. Force decay profiles from the specimens were derived using a Maxwell-Weichert model consisting of springs and dashpots. This model allows the orthodontist to predict load magnitude supplied by the chain at activation and at any time during treatment. PMID- 7864468 TI - Determinants of emergency department use by ambulatory patients at an urban public hospital. AB - STUDY OBJECTIVE: To determine emergency department patients' perceptions of their illness urgency, their attempts to get care elsewhere, and the proportion of patients referred to the ED. DESIGN: Cross-sectional design with self administered questionnaires or interviews. SETTING: Public hospital in Los Angeles County, California. PARTICIPANTS: Consecutive ambulatory patients totaling 1,190. RESULTS: Most patients thought that they required immediate medical attention, even if they said that their condition was not serious, painful, or debilitating. Half of all patients sought care elsewhere before coming to the ED, and 38.2% had seen a doctor. Forty-four percent of all patients said they were referred to the ED by a doctor or a nurse. Referred patients had illness acuteness similar to that of patients who came to the ED on their own. CONCLUSION: In addition to their lack of access to other providers, patients' perceived need for immediate care and referrals by health professionals contribute to ED use for nonemergency conditions. PMID- 7864469 TI - Emergency medicine residency faculty scheduling: current practice and recent changes. AB - STUDY OBJECTIVE: To assess current emergency medicine faculty scheduling practices, preferences, and recent changes. DESIGN: Mail survey. PARTICIPANTS: All emergency medicine residency program directors and full-time faculty. INTERVENTIONS: Questions were asked about current faculty scheduling practices, preferences, and recent changes. RESULTS: Eighty-five percent (79 of 93) of the programs and 63% (606 of 961) of the full-time faculty responded. Faculty most commonly worked a combination of 8- and 12-hour shifts. Seventy-five percent of full-time faculty stated that they would prefer to work 8-hour shifts. Eighty three percent of those who work some or all 8-hour shifts preferred 8-hour shifts; 21% of those working 12-hour shifts preferred the same (P < .0005; test of proportions difference, 62%; 95% confidence interval, 55% to 69%). Over the past 5 years, 40% of programs had shortened shift lengths, and the number of night shifts worked per month and/or the number of nights in a row worked per faculty decreased for 34%. CONCLUSION: Residency faculty prefer and have moved toward working shorter shifts. They are also working fewer night shifts per month and fewer night shifts in a row. PMID- 7864470 TI - Conference attendance: do we meet the new residency review committee requirements? AB - STUDY OBJECTIVES: To characterize the attendance at and presenters of conferences given to emergency medicine residents and to determine the ability of emergency medicine residents to attend conferences while working in the emergency department and on off-service rotations. DESIGN: Descriptive study of an anonymous mail survey. PARTICIPANTS: Residency directors of all approved emergency medicine residency programs in the United States. RESULTS: Seventy-six of 95 questionnaires (80%) were returned. We defined "high attendance" at emergency medicine conferences as a reported average of at least 75% attendance by emergency medicine resident physicians. Fifty percent of respondents reported high attendance. Conversely, 17% of programs reported poor attendance, which we defined as an average attendance by 50% or fewer emergency medicine resident physicians. Forty-eight percent of programs reported that emergency medicine faculty conducted more than 50% of the conferences, and 16% reported that the faculty conducted 25% or fewer conferences. Ninety-six percent of programs allowed residents to attend conferences during off-service rotations. Ninety-two percent of programs relieved residents of clinical responsibilities during scheduled shifts in the emergency department so that they might attend lectures. CONCLUSION: We found that a sizable proportion of programs may not have met the new Residency Review Committee requirements for lecture attendance at the time the guidelines were issued. The vast majority of programs met guidelines for relief of clinical duties, and a large proportion of programs exceeded the requirements for percentage of lectures given by emergency medicine faculty. PMID- 7864471 TI - Subcuticular sutures and the rate of inflammation in noncontaminated wounds. AB - STUDY OBJECTIVE: To determine whether buried, absorbable, subcuticular sutures increase the degree of inflammation in noncontaminated wounds. DESIGN: Randomized, blinded, prospective trial. SETTING: Laboratory. PARTICIPANTS: Eleven Sprague-Dawley rats weighing 300 to 325 g. INTERVENTIONS: Four wounds were made on each rat. Two wounds on each were closed with three interrupted buried, absorbable, subcuticular sutures 6-0 polyglactin 910 and running 5-0 nylon skin sutures. The other two wounds were closed with running 5-0 nylon skin sutures alone. RESULTS: Fourteen days after the sutures were placed, the animals were killed, and histologic preparations were made from each wound. Each sample was scored on a scale of 0 to 3 for the presence of inflammatory infiltrates, fibroplasia and capillary proliferation, necrosis, exudates, giant cells, and edema. We determined a total wound score by adding the scores from each category. The mean total wound score was 4.46 +/- 2.92 for those closed with buried, absorbable, subcuticular sutures and 4.91 +/- 2.56 for those closed without buried, absorbable, subcuticular sutures. Using the Wilcoxon rank-sum test, we found no statistically significant difference in mean total wound score of wounds closed with and without buried, absorbable, subcuticular sutures (alpha = .01). The probability of detecting a twofold difference in total wound scores was 60% (beta = .40). CONCLUSION: Buried, absorbable, subcuticular sutures do not significantly increase the degree of inflammation in noncontaminated wounds. PMID- 7864472 TI - Safety and efficacy of nebulized racemic epinephrine in conjunction with oral dexamethasone and mist in the outpatient treatment of croup. AB - STUDY OBJECTIVE: To identify patients with croup who after treatment with nebulized racemic epinephrine, oral dexamethasone, and mist may be safely discharged home after a period of observation. DESIGN: Prospective interventional. SETTING: Urban children's hospital emergency department. PARTICIPANTS: Children with croup who received racemic epinephrine for the treatment of stridor at rest. INTERVENTIONS: After treatment with .5 mL racemic epinephrine, .6 mg/kg dexamethasone PO, and mist, patients who were assessed as being safe for discharge after 3 hours of observation were discharged home and contacted for 48-hour follow-up. RESULTS: Fifty-five patients with croup were treated with racemic epinephrine. Thirty patients (55%) had sustained responses and were discharged home after 3 hours of observation. No recurrence of respiratory distress and no return visits for medical care were reported (95% confidence interval, 0% to 8.0%). CONCLUSION: Patients with croup who are treated with racemic epinephrine, oral dexamethasone, and mist may be safely discharged home if the patient is assessed as ready for discharge after 3 hours of observation. PMID- 7864473 TI - Home use of syrup of ipecac is associated with a reduction in pediatric emergency department visits. AB - STUDY OBJECTIVE: To determine whether home use of syrup of ipecac is safe and effective in reducing pediatric emergency department visits. DESIGN: Retrospective, multicenter comparison based on secondary use of a large database. PARTICIPANTS: Children younger than 6 years after acute, accidental ingestion of a pharmaceutical product. INTERVENTIONS: 1990 Data corresponding to the study patients from seven regional poison centers were obtained from the American Association of Poison Control Centers. Poison center management choices (particularly use of syrup of ipecac for home decontamination) and characteristics (distribution of pharmaceutical ingestions managed, work volume per staff, staff experience, and training of decision-making director) were analyzed for their impact on the decision to refer a patient to a health care facility or to manage the patient at home. Statistical techniques included weighted least-squares regression analysis using logistic transformation of dependent variables and the forward selection procedure. Adverse patient outcome was defined as moderate effect, major effect, or death (American Association of Poison Control Centers coding criteria). RESULTS: In all, 55,436 children were included in the analysis (range, 3,839 to 12,691 per poison center). The distribution of medications ingested was similar among centers. Increased home use of syrup of ipecac, decreased frequency of ingestion of "high-risk" drugs, and increased staff experience were associated with decreased referral to a health care facility (P < .0001 for each variable). The forward selection procedure determined that syrup of ipecac use explained 45% of the variation in the poison center referral rates. The percentage of drugs defined as high-risk accounted for an additional 31%, and staff experience accounted for another 10% of the variation. Outcome of patients was excellent. No child died. Two home managed patients had a major effect, and 26 had a moderate effect. CONCLUSION: Centers that recommended home use of syrup of ipecac more frequently were able to manage childhood poisoning more cost-effectively, without a decrease in safety. Although increased home management was strongly associated with syrup of ipecac use, the reason for this relationship cannot be determined from the data. Management by experienced professionals also contributed to cost-effectiveness. PMID- 7864474 TI - Ten-year review of pediatric bathtub near-drownings: evaluation for child abuse and neglect. AB - STUDY OBJECTIVE: To evaluate the risk factors associated with bathtub submersion injury and their relationship to child abuse and neglect. DESIGN: Retrospective chart review. SETTING: An urban children's hospital. PARTICIPANTS: Any child sustaining a bathtub near-drowning over the 10-year period from 1982 to 1992. INTERVENTIONS: None. RESULTS: Twenty-one patients were treated for bathtub near drownings during the 10-year period, accounting for 24% of all submersion injuries. A significant number (67%) had historic and/or physical findings suspicious for abuse or neglect, including incompatible history for the injury, other physical injuries, previous child abuse reports, psychiatric history of the caretaker, and/or psychosocial concerns noted in the chart. The mortality rate of 42% was significant. No demographic characteristics identified the children at risk. CONCLUSION: Many children who are injured in the bathtub suffer from abuse or neglect. Medical evaluation should include social work consultation and a search for other accompanying injuries. PMID- 7864475 TI - Emergency department poison advice telephone calls. AB - STUDY OBJECTIVE: Requests for medical advice regarding treatment of poisonings are common in emergency departments. Although there are designated poison centers (PCs), most EDs are recognized by the community and medical staff as a poison information resource. The purpose of this study was to evaluate the accuracy and consistency of poison information given by ED personnel. DESIGN: A prospective, stratified-sample, telephone survey over a 6-month period of requests for medical advice about simulated poison ingestions. PARTICIPANTS: Fifty-two hospital EDs in urban and rural Illinois, all three PCs in Illinois, and three PCs from Indiana, Wisconsin, and Michigan. RESULTS: Hospital EDs responded correctly to only 100 of 156 calls (64.2%). PCs responded correctly to 17 of 18 calls (94.4%), whereas teaching hospitals responded correctly to 15 of 30 calls (50%, P = .002). ED night shift personnel were 5.5 times more likely to respond incorrectly than were personnel on other shifts (95% confidence interval, 2.72 to 11.12). Forty-eight percent of all calls to EDs resulted in advice to call the regional PC. CONCLUSION: Poison advice by ED personnel proved to be inaccurate and inconsistent. As a result, patients may be better served if advice calls are redirected to regional PCs. PMID- 7864476 TI - Prevention of oral dichlorvos toxicity by different activated charcoal products in mice. AB - STUDY OBJECTIVE: To determine whether immediate treatment with oral activated charcoal (AC) products of differing surface areas prevents clinical toxicity of a lethal oral dose of dichlorvos in mice. DESIGN: An in vivo, prospective, randomized, placebo-controlled study using 75 male albino mice. INTERVENTIONS: Fasting mice were administered 57.5 mg/kg of a 0.55% dichlorvos solution via feeding tube. One minute later, groups of 15 mice each received 1 or 2 g/kg of Actidose-Aqua AC or 1 or 2 g/kg of Sigma AC or sterile water by feeding tube. In this way, all mice received 15 mL/kg of an AC suspension or sterile water. The animals were observed for 24 hours for seizures or death. RESULTS: In all treatment groups, mice were found to have significantly fewer seizures and deaths (P < .05) than the control group when compared by chi 2 and Fisher's exact tests. No statistical difference was found between the death and seizure rates when treatment groups were compared with each other. The group sizes were too small, however, to rule out significant type II error (beta > .2). CONCLUSION: In this in vivo mouse model, all AC products tested decreased the incidence of seizures and death. Further studies should be done to investigate the clinical effects of AC products with different surface areas. PMID- 7864477 TI - Correlation of drug pharmacokinetics and effectiveness of multiple-dose activated charcoal therapy. AB - STUDY OBJECTIVE: To evaluate an animal model of multiple-dose activated charcoal (MDAC) therapy and correlate the pharmacokinetic properties of four drugs with the efficacy of MDAC. DESIGN: Prospective, randomized, controlled, crossover design. SETTING: A university animal research facility. PARTICIPANTS: Seven female pigs (15 to 22 kg) with an indwelling central venous line and gastrostomy tube. INTERVENTIONS: Acetaminophen (30 mg/kg), digoxin (30 micrograms/kg), theophylline (8.9 mg/kg), and valproic acid (18 mg/kg) were simultaneously administered intravenously over 12 minutes. In the experimental arm, 25 g activated charcoal was administered at 0, 2, 4, 6, 12, 18, 24, and 30 hours through the gastric tube. In the control arm, an equal volume of water was given at the same times. Blood specimens were obtained over 36 hours to measure serum drug concentrations. RESULTS: Each drug exhibited enhanced elimination (P < .01) in the MDAC group except valproic acid. Lower intrinsic clearance was correlated (P < .05) with increased systemic elimination during the charcoal arm. Volume of distribution, half-life, and protein binding were not significantly correlated with charcoal-enhanced systemic drug elimination. CONCLUSION: The response of a drug to MDAC may be affected by its intrinsic clearance. The restrictive nature of the protein binding of valproic acid may be responsible for its lack of response. Results with the porcine model are consistent with the effects observed in human beings. PMID- 7864478 TI - Therapy of brown spider envenomation: a controlled trial of hyperbaric oxygen, dapsone, and cyproheptadine. AB - STUDY OBJECTIVE: To determine whether hyperbaric oxygen (HBO), dapsone, or cyproheptadine decreases the severity of skin lesions resulting from experimental Loxosceles envenomation. DESIGN: Randomized, blinded, controlled study. SETTING: Animal care facility. INTERVENTIONS: We used New Zealand white rabbits. All groups received 20 micrograms of pooled L deserta venom intradermally. Our control group received 4 ml of a 5% ethanol solution by oral gavage every 12 hours for 4 days. The HBO group received hyperbaric oxygen at 2.5 ATA for 65 minutes every 12 hours for 2 days, plus 5% ethanol solution for 4 days. The dapsone group received dapsone 1.1 mg/kg in 5% ethanol by gavage every 12 hours for 4 days. The cyproheptadine group received cyproheptadine .125 mg/kg in 5% ethanol by gavage every 12 hours for 4 days. RESULTS: Total lesion size and ulcer size were followed for 10 days. The lesions were then excised, examined microscopically, and ranked by the severity of the histopathology. The groups did not differ significantly with respect to lesion size, ulcer size, or histopathologic ranking. CONCLUSION: Given the negative result in this study with adequate power to detect meaningful treatment benefits, we cannot recommend hyperbaric oxygen, dapsone, or cyproheptadine in the treatment of Loxosceles envenomation. PMID- 7864479 TI - Treatment of verapamil overdose with glucagon in dogs. AB - STUDY OBJECTIVE: The purpose of this study was to evaluate the effectiveness of glucagon as a treatment for the hemodynamic effects of verapamil overdose in a canine model. DESIGN: The study was performed in a nonblinded, controlled animal model. INTERVENTIONS: Pentobarbital-anesthetized and instrumented dogs were maintained and observed for 60 minutes or until death. All animals were overdosed with 15 mg/kg i.v. verapamil over 30 minutes. Mean arterial pressure, heart rate, ECG, and cardiac output were monitored. The experimental group received a 2.5 mg glucagon i.v. bolus followed by a glucagon drip at 2.5 mg/hr. The control group received an equal volume of i.v. normal saline solution in the same fashion. Analysis was performed with the Dunnett and Tukey-Kramer methods, with alpha set at .05. RESULTS: There were eight experimental and seven control animals, with mortality rates of 0% and 29%, respectively. The experimental group had increases in cardiac output and heart rate that were statistically significant at 45 and 60 minutes compared with those of the control group. In addition, there was a significant difference in heart rate at 30 minutes. No difference was noted between the groups for mean arterial pressure. CONCLUSION: Glucagon appears to reverse both the bradycardia and the depressed cardiac output associated with verapamil overdose in a canine model. PMID- 7864480 TI - Abdominal compressions increase vital organ perfusion during CPR in dogs: relation with efficacy of thoracic compressions. AB - STUDY OBJECTIVE: Abdominal compressions can be interposed between the thoracic compressions of standard CPR (SCPR). The resulting interposed abdominal compression CPR (IAC-CPR) may increase blood pressures and patient survival, particularly if applied as a primary technique after in-hospital cardiac arrest. We used a predominant cardiac compression canine model to study the effects of IAC-CPR on blood pressures and total and vital organ perfusion as a function of time after cardiac arrest and efficacy of SCPR. DESIGN: In a crossover design, we measured blood pressures and total and regional blood flow (radioactive microspheres) during 6-minute episodes of mechanical SCPR and IAC-CPR, both early (4 to 16 minutes) and late (18 to 30 minutes) after induction of ventricular fibrillation in eight dogs (weight, 25 to 33 kg) under neuroleptanalgesia/anesthesia. RESULTS: During IAC-CPR, the ascending aortic right atrial pressure gradient increased (P < .05), and retrograde pressure pulses contributed to the rise of ascending aortic pressure. Within 2 minutes after the start of IAC-CPR, end-tidal CO2 fraction increased by 0.6 +/- 0.4 vol% (P < .05), suggesting enhanced venous return. IAC-CPR enhanced (P < .05) total forward blood flow (574 +/- 406 versus 394 +/- 266 mL/minute during SCPR for the early phase) and vital organ perfusion (including myocardium), in both early and late phases. The IAC-CPR-induced augmentation of blood flow was greater if perfusion was relatively high during SCPR. CONCLUSION: Compared with predominant cardiac compressions alone (SCPR), the addition of interposed abdominal compressions (IAC-CPR) improves total and vital organ oxygen delivery through enhanced venous return and perfusion pressures. PMID- 7864481 TI - Automatic mechanical device to standardize active compression-decompression CPR. AB - STUDY OBJECTIVE: To develop an automatic mechanical device capable of performing active compression-decompression (ACD) CPR in laboratory animals. DESIGN: A swine model was used to study standard and ACD CPR. One-minute periods of standard mechanical chest compressions were alternated with mechanical ACD CPR. SETTING: University hospital laboratory. INTERVENTIONS: A commercially available device that provided standard chest compressions only was modified to deliver ACD CPR. RESULTS: The absolute difference in intrapleural pressure and tidal volume almost doubled during ACD CPR compared with that with standard CPR. CONCLUSION: The presence of a greater negative change in intrapleural pressure confirmed that active decompression of the chest had occurred and that the device was capable of performing ACD CPR. The device provides consistent rate, depth, force, and duty cycle. PMID- 7864482 TI - Group A streptococcal tonsillopharyngitis: cost-effective diagnosis and treatment. AB - Most patients who seek medical attention for sore throat are concerned about streptococcal tonsillopharyngitis, but fewer than 10% of adults and 30% of children actually have a streptococcal infection. Group A beta-hemolytic streptococci (GAS) are most often responsible for bacterial tonsillopharyngitis, although Neisseria gonorrhea, Arcanobacterium haemolyticum (formerly Corynebacterium haemolyticum), Chlamydia pneumoniae (TWAR agent), and Mycoplasma pneumoniae have also been suggested as possible, infrequent, sporadic pathogens. Viruses or idiopathic causes account for the remainder of sore throat complaints. Reliance on clinical impression to diagnose GAS tonsillopharyngitis is problematic; an overestimation of 80% to 95% by experienced clinicians typically occurs for adult patients. Overtreatment promotes bacterial resistance, disturbs natural microbial ecology, and may produce unnecessary side effects. Existing data suggest that rapid GAS antigen testing as an aid to clinical diagnosis can be very useful. When used appropriately, it is sensitive (79% to 88%) in detecting GAS-infected patients and is specific (90% to 96%) and cost-effective. Penicillin has been the treatment of choice for GAS tonsillopharyngitis since the 1950s; 10 days of treatment are necessary for bacterial eradication. A single IM injection of benzathine penicillin is effective and obviates compliance issues. Until the early 1970s, the bacteriologic failure rate for the treatment of GAS tonsillopharyngitis ranged from 2% to 10% and was attributed to chronic GAS carriers. Since the late 1970s, the penicillin failure rate has frequently exceeded 20% in published reports. Explanations for recurrent GAS tonsillopharyngitis include poor patient compliance; reacquisition from a family member or peer, copathogenic colonization by Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, anaerobes that inactivate penicillin with beta lactamase, or all these organisms; suppression of natural immune response by too early administration of antibiotics; GAS tolerance to penicillin; antibiotic eradication of normal pharyngeal flora that normally act as natural host defenses; and establishment of a true carrier state. When therapy fails, milder symptoms may occur during the relapse. Several antimicrobials have demonstrated superior efficacy compared with penicillin in eradicating GAS and are administered less frequently to enhance patient compliance. In previously untreated GAS throat infections, cephalosporins produce a 5% to 22% higher bacteriologic cure rate; after a penicillin treatment failure, these differences are greater. Amoxicillin/clavulanate and the extended-spectrum macrolides clarithromycin and azithromycin may also produce enhanced bacteriologic eradication in comparison to penicillin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7864483 TI - Acute pharyngitis: the case for empiric antimicrobial therapy. PMID- 7864484 TI - A survey of wellness issues in emergency medicine (Part 3). PMID- 7864485 TI - Bronchial rupture caused by blunt chest injury. AB - We have surgically treated six patients with bronchial rupture caused by blunt chest injury in the past 5 years. All injuries resulted from traffic accidents, except in one patient who was hit by a crane. Clinical manifestations included chest pain (n = 6), subcutaneous emphysema (n = 4), and dyspnea (n = 6). Roentgenographic findings were tension (n = 3) or nontension (n = 3) pneumothorax, subcutaneous emphysema (n = 4), pneumomediastinum (n = 3), deep cervical emphysema (n = 5), and delayed collapse of the affected lung (n = 3). Three patients had associated injuries: right clavicle and rib fractures in the first; right humeral, scapular, and multiple rib fractures and left sternoclavicular joint dislocation in the second; and left clavicle fracture in the third. These six patients all underwent immediate tube thoracostomy and then bronchoplasty. Bronchoplasty was performed within 3 days in four patients and on days 16 and 30, respectively, in the other two patients. The affected lung demonstrated full expansion in all patients immediately after bronchoplasty. Follow-up bronchoscopy showed good patency of all bronchi. PMID- 7864486 TI - Development of ventricular fibrillation after intravenous calcium chloride administration in a patient with supraventricular tachycardia. AB - The i.v. administration of calcium before or shortly after treatment of supraventricular tachycardia with verapamil has been suggested to counteract a hypotensive response to verapamil. We discuss the case of a patient who presented to the emergency department with an accelerated wide-complex tachycardia and minimal symptoms. Immediately after i.v. administration, of 1 g calcium chloride as pretreatment for verapamil administration, ventricular fibrillation developed. Emergency physicians should be aware of potential dangers after the administration of i.v. calcium preparations when trying to prevent known hypotensive side effects of i.v. verapamil administration. PMID- 7864487 TI - Lateral sinus thrombosis complicating mastoiditis. AB - Although otitis media is easily recognized in the emergency department, its complications can often be missed. We present the case of a patient with mastoiditis with lateral sinus thrombosis that was not diagnosed until a digital subtraction angiogram revealed the occlusion. PMID- 7864488 TI - Spontaneous aortocaval fistula. AB - Rupture of an abdominal aortic aneurysm into the inferior vena cava is uncommon. A classic syndrome of high-output heart failure, continuous abdominal bruit, and renal insufficiency has been described and permits a clinical diagnosis if an aortocaval fistula is considered in the differential diagnosis. Classic signs and symptoms can be misinterpreted and are present in less than 50% of cases. Physicians should consider abdominal ultrasonography and aortography in stable patients, followed by prompt surgical intervention. We report the case of a patient with an aortocaval fistula. PMID- 7864489 TI - Sherlayne's braids. PMID- 7864490 TI - Serum alcohol is not the same as blood alcohol concentration. PMID- 7864491 TI - Tracheal lidocaine stops airway hyperresponsiveness. PMID- 7864492 TI - Rapid-sequence induction technique for orotracheal intubation of adult nontrauma patients in a community hospital setting. PMID- 7864493 TI - The "new" ACLS: course creativity and flexibility. PMID- 7864494 TI - Acute myocardial necrosis associated with spontaneous right pneumothorax. PMID- 7864495 TI - Expired carbon dioxide monitoring. American College of Emergency Physicians. PMID- 7864496 TI - Antitrust. American College of Emergency Physicians. PMID- 7864497 TI - Emergency medicine and domestic violence. American College of Emergency Physicians. PMID- 7864498 TI - [Interview with Jacques Toubon, the Minister of Affaires Culturelles et de la Francophonie. What is the future of the French language in the medical and scientific community?]. PMID- 7864499 TI - [Diabetic pregnancy. Evaluation and prospects from the study of 212 diabetic pregnancies followed-up between 1985 and 1992]. AB - A total of 212 diabetic pregnancies were studied prospectively over the period 1985 to 1986, included: 76 insulinodependent diabetics (IDD), 34 non insulinodependent diabetics (NIDD), and 102 gestational diabetes. The perinatal mortality rate for all diabetic pregnancies was 1.4% (n = 3); 3 congenital malformations were recorded (a therapeutic abortion was performed in 2 cases). These results are comparable with those of the non diabetic population. However, it is to be noticed that maternal as well as neonatal morbidity was important (hypoglycaemic comas: 18 in 9 IDD, preeclampsia: 7 IDD, 2 NIDD, 1 DG; caesarean delivery: 50% IDD, 50% NIDD, 25% DG; neonatal morbidity 20% of the new born. The main objectives must be targeted on the prevention of severe hypoglycaemia in IDD, the early diagnosis of DG and the development of pregnancy care in NIDD. PMID- 7864500 TI - [Clinical and epidemiological aspects of Horton disease based on survey methods in ophthalmology or internal medicine]. AB - We conducted a retrospective study of 29 consecutive cases of temporal arteritis, all with definite histological diagnostic criteria. The epidemiological aspects of the main clinical and biological features were compared according to their mode of recruitment, the patients being hospitalized either in an ophthalmological unit (n = 15), or in an Internal Medicine unit (n = 14). The level of fever and of sedimentation rate were significantly less in the ophthalmological group (respectively p < 0.001 and p < 0.02), a third of which is represented by the purely ophthalmological manifestation called "occult temporal arteritis". Among the ophthalmological manifestations, despite the fact that the recruitment bias prevented any strict epidemiological comparison, we were surprised to find no significant difference between the two groups concerning the frequency of transient ophthalmological manifestations, which confirmed in half the patients their reputation of forerunners of irreversible lesions. Thus, the presentation of temporal arteritis differs according to its ophthalmological or Internal Medicine recruitment. We were unable to determine a precise chronology difference in the principal manifestations between these two groups. The severity of the ocular manifestations justifies looking for temporal arteritis in all cases of transient ophthalmological manifestations, even if clinically totally isolated. PMID- 7864501 TI - [Treatment of mucositis with vitamin E during administration of neutropenic antineoplastic agents]. AB - Mucositis represents one of the most frequent complications during chemotherapy or radiotherapy. Few studies have showed effective prevention against mucositis in this setting. In this randomized study, we tested the efficacy of vitamin E in the treatment of chemotherapy-induced mucositis. Twenty patients with malignant haemopathies were included; 19 patients were evaluable for the prevention of mucositis. Ten patients were treated with induction therapy for acute myelogenous leukaemia and 9 were treated with intensive therapy followed by autologous bone marrow transplantations. The severity of mucositis was evaluated according to World Health Organization classification. Our results showed that vitamin E may be of therapeutical value in the prevention of mucositis especially during induction therapy for acute myelogenous leukaemia. PMID- 7864502 TI - Should travellers in rabies endemic areas receive pre-exposure rabies immunization? AB - A questionnaire survey was conducted in 1,882 foreign travellers, 74% of which were Europeans, after being in Thailand for an average of 17 days, about the history of potential rabies exposure during their visits. Dog bite and dog lick were experienced in 1.3% and 8.9% of the travellers respectively. The exposed individuals tended to stay in Thailand longer and the incidents occurred mainly in cities rather than in the rural areas. Thirty-one (1.6%) of all travellers had a history of rabies vaccination, 9 as a result of dog bite or dog lick in Thailand whereas the remaining 22 had already received the vaccine prior to coming to Thailand. Such high prevalences of potential rabies exposure and rabies vaccination may justify the inclusion of rabies vaccine into the multiple vaccination program for travellers to rabies endemic countries. This was favoured by over half of the travellers interviewed. PMID- 7864503 TI - [Anatomo-clinical conference. Hopital de la Pitie-Salpetriere. Case no. 3-1994. Cerebrovascular accident, endobronchial granuloma and fatal hemoptysis in a 87 year-old woman]. PMID- 7864504 TI - [African histoplasmosis: clinical and therapeutic aspects, relation to AIDS. Apropos of 4 cases, including a case with HIV-1-HTLV-1 co-infection]. AB - The authors report 4 cases of African histoplasmosis in Zairans. The diagnostic was based ou cutaneous (4 patients), bones (3), lymph-nodes (2), and bowel localizations (1) and was confirmed by the presence of Histoplasma duboisiis yeasts in cutaneous biopsy (4 patients), in pus of abscess or cutaneous lesions (3) and in stools (1). Two HIV seronegatives patients had a good outcome with amphotericin B. One patient died without any treatment. One HIV-1 and HTLV-1 seropositive patient had successful short-term outcome with ketoconazole. Seven others cases of association between African histoplasmosis and AIDS are noted in the literature. They suggest the opportunistic nature of this deep mycosis. PMID- 7864505 TI - [Epidemiology of chemoresistant Plasmodium falciparum]. PMID- 7864506 TI - [New approach to arterial hypertension: study of short-term blood pressure variability. Values and prognostic implications: preliminary data]. PMID- 7864507 TI - [Pasteurella multocida septicemia and infections of ascitic fluid in patients with liver cirrhosis]. PMID- 7864508 TI - [Pasteurella multocida septicemia in a patient with liver cirrhosis]. PMID- 7864509 TI - [Cytomegalovirus colitis in an immunocompetent patient]. PMID- 7864510 TI - [Severe acute alcoholic hepatitis after corticoid withdrawal]. PMID- 7864511 TI - Filtration of cerebrospinal fluid in acute inflammatory demyelinating polyneuropathy (Guillain-Barre syndrome). AB - INTRODUCTION: Acute Guillain-Barre syndrome (GBS) is a disease where cell mediated and humoural immune reactions play a key role. Breakdown of the blood nerve barrier, inflammation of the nerve roots and conduction block are leading symptoms. As it is likely that pathological humoural or cellular factors are concentrated in the subarachnoid space and since factors in the cerebrospinal fluid (CSF) of GBS patients were shown to block sodium channels, a direct therapeutic intervention in the intrathecal compartment seemed worthwhile. METHODS: For this purpose, we developed a technique to purify CSF from pathological factors. Filtration was achieved by withdrawal of CSF (through a lumbally inserted 18 G catheter) and reinfusion via specially developed filters. RESULTS: Twenty severely affected GBS patients were treated with 4 to 38 CSF filtrations. This eliminated cells (> 99%) and reduced the protein content. Clinical improvement was achieved probably by improvement of nerve conduction following a reduction of sodium channel blocking factors. The median time to one grade improvement was 19 days, to reach grade 2 (independent walking) was 42 days. Ventilated patients were weaned from the ventilator after 16 days (median). Patients for which CSF filtration was the first kind of treatment improved faster than patients that had not responded to other treatments, such as plasma exchange or intravenous immunoglobulins. DISCUSSION AND CONCLUSION: Severe side effects were not observed, except sometimes transient headache during the withdrawal phase. This therapy seams to shorten treatment time (in comparison to times reported in studies with and without GBS-specific treatment by plasma exchange or immunoglobulins) and to reduce the degree of remaining neurological deficits. An open randomized controlled study is currently being conducted to compare CSF filtration with plasma exchange. PMID- 7864512 TI - Sex hormones in chronic systemic lupus erythematosus. Correlation with clinical and biological parameters. AB - Sex hormones may play a major role in the pathogenesis and course of systemic lupus erythematosus (SLE). OBJECTIVE--To evaluate the immunoregulatory effect of gonadal steroids in SLE and their mechanisms of action, and to establish a correlation with the clinical and biological activity. DESIGN--Cross-sectional study of a cohort with SLE. SETTING--Outpatient SLE clinic. PATIENTS--27 patients with chronic SLE, 14 were fertile women, 8 postmenopausal women and 5 men. MEASUREMENT--Serum gonadotropins (FSH, LH), prolactin (PRL), progesterone (PG), testosterone (T), estradiol (E2) and total urinary estrogens (UE) were studied in SLE patients and in 35 healthy controls of similar age and sex. Blood and urine samples of several days of the study cycle were obtained for hormonal assay. RESULTS--An increased LH activity was observed in all groups of patients. There were no changes in serum T levels, but absence of steroid therapy increased their levels in fertile women. A decrease in E2 values in the fertile women was observed, but total UE was similar to those in controls. This suggests an alteration in intermediate estrogen metabolism. Men with SLE showed a higher levels in PG and UE than controls. Also, in both groups of women on steroid treatment, a decrease of PRL was observed compared to the controls. In the fertile women in luteal phase, there was a decrease in PG. In the fertile women with higher clinical activity in the midcycle phase, and those with higher biological activity in the luteal phase, a decrease in serum E2 was seen. CONCLUSIONS--Our results support the hypothesis that there is an alteration of intermediate metabolism of the estrogens and of the testosterone. As well, a lower production of PRL during steroid treatment, and a lower production of PG may be important contributing factors in immunomodulation of SLE. Mechanism for this action should be mediated through a stimulation of the gonadotropins as LH. PMID- 7864513 TI - Safety of pentamidine prophylaxis for Pneumocystis carinii pneumonia on the endocrine pancreatic function in HIV patients. AB - We assessed the pancreatic beta cells function of HIV patients receiving either 300 mg per month of aerosolized pentamidine (n = 12) or oral trimethoprim sulfamethoxazole (TMP-SMX), twice a day three times per week (TMP: 160 mg, SMX: 800 mg) (n = 10). Intravenous (i.v.) glucose tolerance tests were performed after i.v. injection of 0.5 glucose by kg of body weight in 30 seconds. Plasma insulin levels were assessed at baseline, 1, 2, 3 and 5 min. Moreover, in patients receiving inhaled pentamidine, plasma glucose amylase and insulin levels were measured every 30 min for 2 hours after the end of the aerosol. Plasma pentamidine levels were measured 30 min after the end of the aerosol. Those tests were performed every 2-3 months for one year. In most patients taking aerosol treatment, pentamidine levels were detectable, remaining under levels of 50 ng/ml. Pentamidine plasma levels increased in a time dependent manner. Baseline plasma glucose, amylase and insulin levels were in normal range and remained stable during the therapy. For 7 out of 12 patients, glucose tolerance tests showed an adequate insulin secretion: the addition of the two best insulin levels were higher than 70 IU/ml. When this criteria was not found (n = 5), a glucagon stimulation test allowed to exclude an endocrine pancreatic dysfunction. Due to its apparent short half-life, increased pentamidine levels could be related to an improvement of spray techniques as well as to a cumulative effect. Pancreatic function was preserved in pentamidine-treated patients compared to TMP-SMX treated patients. PMID- 7864514 TI - Interview with Pier-Luigi Meroni. What is going to happen tomorrow in the field of anti-endothelial cell autoantibodies related to vasculitis? PMID- 7864515 TI - [Use of English in French scientific publications]. PMID- 7864516 TI - [Latrodectism in Corsica. Study of 15 cases]. AB - Malmignate bites are rare in Corsica nowadays. The authors report 15 cases of latrodectism in patients hospitalized between 1986 and 1993 at the Ajaccio hospital in southern Corsica. The disease has a polymorphous expression. We investigated the frequency and the specificity of the symptoms. Eleven clinical signs and 2 biological signs enabled us to describe 3 categories: specific, moderately specific, non-specific. Most of the signs described in the literature were found in this study, as well as a concordant frequency. We notice, though, that the latrodectesmica facies was not often observed in this series. No serious complication occurred. PMID- 7864517 TI - [Longitudinal stress fractures of the tibia. Apropos of 3 cases]. AB - Longitudinal stress fractures of the tibia are rare: only 16 cases have been published. We report three cases, in two men aged 54 and 70 years and in one women aged 73. The patients had pain when bearing weight on the affected limb. The pain increased over a few weeks. A diagnosis of arthritis of the ankle joint was entertained in 2 cases. Among the three patients, one was suffering from rheumatoid arthritis and had had Ender nails due to fracture of the femoral neck of the same limb. The longest delay for diagnosis was six months. Plain radiographs were normal in two cases. A technetium 99m MDP bone scan showed increased uptake of the whole shaft of the tibia in one patient, on the lower end of the tibia in two others. Computed tomography was performed in two cases and showed the stress fracture. Diagnosis was often delayed because clear changes at plain X-ray examination, periostal reaction often being delayed. Technetium 99m bone scan early showed increased uptake. CT scan showed callus formation and sometimes the fracture itself. MRI has been studied little. PMID- 7864518 TI - [Anatomo-clinical conference. Hopital de la Pitie-Salpetriere. Case No. 4-1994. Chronic diarrhea in a patient with lupus]. PMID- 7864519 TI - [Elementary lesions and pathological classification of interstitial lung diseases]. PMID- 7864520 TI - [Tamoxifen and cardiovascular risk]. PMID- 7864521 TI - [Intestinal complications of non-steroidal anti-inflammatory agents]. PMID- 7864522 TI - [Thrombotic microangiopathy and Listeria monocytogenes septicemia disclosing human immunodeficiency virus infection]. PMID- 7864523 TI - [Malabsorption syndrome caused by digestive amyloidosis. Uncommon manifestation of light chain myeloma in a 38-year-old woman]. PMID- 7864524 TI - [Hyperparathyroidism in a patient with neurofibromatosis associated with Steinert's disease]. PMID- 7864525 TI - [Spinal sites, polyneuropathy and meningeal intra-spinal involvement disclosing recurrence of sarcoidosis. Diagnostic value of MRI]. PMID- 7864526 TI - [Corynebacterium diphtheriae endocarditis complicated by arthritis and cerebral abscess]. PMID- 7864527 TI - [Hepatitis C virus and Sjogren syndrome]. PMID- 7864528 TI - [Use of track detector for the measurement of urine plutonium]. AB - In case of internal exposition by inhalation of plutonium compounds, the faecal excretion is many times higher than in urine. In case of emergency, the faecal analysis is, of course, the best control. But in case of chronic exposure, the urine analysis are better tolerated by workers and easier for the laboratory organization. The results presented pertain to Plutonium 239: the chemical separation is quite conventional but a track detection is used for counting. It was first necessary to optimise both, the thickness of the screen placed between the radioactive source and the detector, and the chemical treatment for transforming the tracks into holes. Three minutes were required to count the perforations by moving the detector across a spark system. Due to detector background and efficiency, a 30 day exposure time is required to detect 0.2 mBq of Plutonium 239 (that's enough in relation to legal limits). PMID- 7864529 TI - [Therapeutic applications of genetic engineering]. AB - Technical developments of genetic engineering have been revealed especially interesting in the human therapeutic field. Techniques for gene transfer have been improved to introduce synthetic sequences into the cellular genomes. Candidate cells and culture systems have been screened for their capacity to synthesise the proper recombinant molecules. In the nearest future, high biotechnologies should provide a great quantity of recombinant products, covering a high variety of diseases (clotting factors, cytokines, hormones, monoclonal antibodies, vaccines, thrombolytics). This tendency has been largely initiated, and is accompanied by the quick development of basic sciences such as glycobiology and molecular biology, together with the development of a specific regulatory environment. Besides, genetic engineering offers new therapeutic outlets: transgenic animals, genic therapy, antisense technology. PMID- 7864530 TI - [Absence of chemical interaction between short catheters (ETFE) and three major antibiotics. Study model]. AB - Recourse to sounding with vein catheters is more and more frequent in hospital environments. At the same time, a perceptible increase in incidents and accidents linked to this constantly growing practice is noted. The multiplication of new biomaterials used in the composition of catheters leads to taking into account the criteria of innocuousness and physiochemical inertia as discriminant elements in the choice of biomaterials. A study in vitro has been undertaken of the interaction between short catheters made of ethylenetetrafluoroethylen (ETFE) and antibiotic solutions widely used in hospital environments. The confrontation concerned solutions of vancomycine (Vancocin), ciprofloxacine (Ciflox) and the amoxicillin-clavulanic acid (Augmentin) association. A device has been fitted up and operative conditions have been set in order that the flushing out of the catheters by the solutions be in quality and quantity, as near as possible to actual conditions of use. The interaction marked chosen being a possible release of fluorides ions by the polymer, the determination of this anion has been made by liquid-gas chromatography paired with a flame ionization detection. We show the inertia of ETFE catheters with respect to the solutions examined. Taking into account the initially defined objectives, the conclusion of the work is important and constitutes a considerable factor of security for the catheters user whether he be buyer or practitioner. The model of study making up this approach could very be applied to other categories of materials and therapeutics. PMID- 7864531 TI - [Study of antiviral action of total alkaloids from Haemanthus albiflos]. AB - Investigations were undertaken on the antiviral action level of an alkaloid extract from Haemanthus albiflos bulb, earlier reported as efficient against RNA viruses. Rotavirus propagated on MA 104 cells with different concentrations of the extract was used in the assays. Incidence on cellular and viral RNA synthesis was evaluated by measuring the radioactivity incorporated using labelled precursors. An inhibition of 42% and 79% of the cellular RNA synthesis was observed when respectively 25 microliters/ml and 50 microliters/ml concentrations of the alkaloid extract were tested. After 20 h incubation a decrease of the viral RNA synthesis was observed. It was of 46%, 36% and 27% compared to the control when respectively 25 microliters/ml, 50 microliters/ml and 100 microliters/ml concentrations of the extract were tested. Besides, the maximum viral production was delayed parallelly to the increase of the extract concentration. A similar viral synthesis inhibition was obtained after only 4 hours incubation suggesting that the extract interfere in the early events of the viral cycle. PMID- 7864532 TI - [Drug addicts in the Netherlands]. AB - Dutch Government admit that tolerate attitude toward lower-risk drug abuse could reduce criminality and protect drug addict's health. Some Dutch psychiatrists disagree and try to struggle against this so called "normalization" politic. Morphine legal consumption, per million inhabitants is higher in Netherlands than in France, showing a certain latitudinarianism of health profession. During last years, illicit traffic data indicate an extensive increase, but drug addicts statistics are no more trustworthy than in France. International Narcotics Control Board (UNO) disapprove of the non application of 1961 Narcotics Convention in Netherlands. Recently dutch authorities suggest french government to develop bilateral cooperation in drug prevention. In fact, Netherlands liberate cannabis consumption which brings, as in other countries an increasing of drug addiction Nevertheless, this liberalization is still recommended by there who ignore the international last century experiences. In a word, acting toward supply and not only towards demand is necessary for a correct prevention as WHO and UNO recommend it. PMID- 7864533 TI - [Did the stage of diagnosis and the surgical management of colonic cancers change over the last ten years? Apropos of 303 patients]. AB - The major prognostic factors in colonic cancer are parietal invasion, lymph node spread and distant metastasis, as summarized in the Dukes classification. The aims of this study were to find any variation of these parameters between patients operated in 1981 and those operated in 1991 and whether the mortality and morbidity rate were modified. One hundred and twenty seven patients in 1981 and 176 in 1991 were considered. Age, sex, clinical features, tumor staging and histologic data were reviewed. Mortality and morbidity rates were established. Mean age was 67 (+/- 14) in 1981 and 69 (+/- 15) in 1991. Obstructing carcinomas were present in 8 cases (7%) in 1981 and 20 (13%) in 1991. At laparotomy, metastases were found in 16 cases (13%) in 1981 and 25 (14%) in 1991. Tumors were resectable in 22 patients (17%) in 1981 and in 23 (14%) in 1991. Tumor staging showed in 105 specimens in 1981: 24 Dukes' A (23%), 39 Dukes' B (37%), 26 Dukes' C (25%) and 16 Dukes' D (15%). In 1991, the study of 153 specimens found 23 Dukes' A (15%), 52 Dukes' B (35%), 54 Dukes' C (36%) and 24 Dukes' D (16%). None of the differences were statistically significant. Overall mortality rate in 1981 was 4.3% (5 patients including two anastomotic leaks) and 6 (5.2%) patients were operated for surgical complications including 5 anastomotic leaks. In 1991, 3 patients (1.7%) were operated and only one for an anastomotic leak. There were no deaths. Mortality and morbidity rates were significantly different (p < 0.05) between 1981 and 1991. As far as Dukes classification is concerned, the prognostic variables of colonic cancers have not changed over this ten-year period. On the other hand, the progress in surgical management allows curative resection without mortality. PMID- 7864534 TI - [Oncological and functional results of direct colo-anal anastomosis after total resection of the rectum for cancer]. AB - From january 1986 to december 1992, 71 patients underwent direct colo-anal anastomosis as described by Parks (CAA) after total rectal resection for carcinoma: 49 men and 22 women with a mean age of 64 years (range 37-82). In 67 cases, the indication was for adenocarcinoma of the mid and low rectum, and in 4 cases for carcinoma of the upper rectum associated with a low rectal benign tumour (6 Dukes A, 36 Dukes B, 21 Dukes C, 8 Dukes D). A diverting colostomy was constructed in all cases. One patient died from pulmonary embolism (mortality: 1.4%). Anastomotic leakage occurred in 6 cases (8.5%). None of these cases required reoperation and all colostomies have been closed. Local recurrence occurred in 12 cases (17%) 6 to 34 months after CAA, of whom 4 were treated by abdominoperineal resection. Eleven patients died from local recurrence (3 cases) or distant metastasis (8 cases). Actuarial survival at 1, 2, 3, 4 and 5 years was 92%, 88%, 78%, 75% and 69% respectively. From the functional point of view, one patient underwent abdomino-perineal resection for incontinence 3 years after CAA. All the other patients were fully continent, with a mean stool frequency of 2 per day, and good gas-stool discrimination. Twenty per cent of patients presented soiling, 20% with stool frequency, and 12% with urgency. Long term functional and oncological results make CAA a good alternative to abdomino-perineal resection for mid and low rectal carcinoma. PMID- 7864535 TI - [Pancreaticojejunal anastomosis by intussusception of an isolated loop in pancreaticoduodenectomy]. AB - The most frequent and severe complication of pancreaticoduodenectomy is pancreatic fistula due to dehiscence of the pancreas anastomosis. The technique that uses a separate Roux en Y loop for pancreas anastomosis, to reduce the fatal risks of pancreatic fistula, has been described for more than 50 years. With the development of pancreaticogastrostomy, it seems interesting to present a procedure using an isolated loop for the pancreas; this technique, derived from those previously described allows a good intussusception of the pancreatic stump into the intestinal loop. This method was performed in 22 pancreaticoduodenectomies. There were 2 operative deaths unrelated to the pancreaticojejunal anastomosis and one pancreatic fistula, which healed under medical treatment. PMID- 7864536 TI - [Clinically occult invasive cancers of the breast. Apropos of 136 cases]. AB - Between 1978 and 1991, one hundred and thirty-six surgical excision biopsies were performed in our institution for clinically occult breast cancers. A retrospective analysis of histopathologic characteristics was carried out in order to determine the prognostic factors of these cancers detected by mammography. Mammographic findings consisted of microcalcifications alone (49 cases), microcalcifications with opacity (20 cases), stellate opacity (52 cases) and well-circumscribed opacity (12 cases). Preoperative localization was achieved by mammography in 109 cases and ultrasonography in 27 cases. The size of malignant lesions ranged from 3 to 25 mm, 76 lesions were less than 10 mm in diameter. The histopathologic findings were as follows: invasive ductal cancer (IDC) 113 cases (83%), invasive lobular cancer (ILC) 11 cases (8%), ductal or lobular cancer in situ with microinvasion 12 cases (9%). Breast conserving treatment was performed in 106 cases (78%). A high proportion of well differentiated tumors was encountered-59 grade I (52%) were identified out of 113 IDC-and the incidence of axillary node metastases was less than 10%. Clinically occult breast cancers seem to exhibit favorable prognostic factors. PMID- 7864537 TI - [Proctectomy for cancer]. PMID- 7864538 TI - [Celiosurgery in gynecology. Indications, benefits and risks]. AB - Initially used exclusively for diagnosis, laparoscopy is now a surgical method in gynecology but also in many other specialties. In gynecology, the results of laparoscopic surgery are comparable to those obtained by laparotomy in many indications: ectopic pregnancy, ovarian cysts, endometriosis, tubo-peritoneal sterility... Because of the advantages of laparoscopic surgery over traditional surgical treatment by laparotomy, operative laparoscopy is, in these indications, now recognized to be the best choice of surgical treatment. The most important advantages of operative laparoscopy are the following: less esthetic drawbacks, minimal risk of parietal and infectious complications, lower risk of post operative adhesions, more comfortable post operative course and lower cost due to considerably shortened hospital stay and recovery period. The risk of complications is directly correlated to the surgeon's experience and the importance of the surgery performed. PMID- 7864539 TI - [Value of celioscopy in non-traumatic acute abdomen]. AB - The diagnostic and therapeutic value of laparoscopy in emergency was studied in 314 patients presenting with non-traumatic acute abdomen. Laparoscopy gave a correct and complete diagnosis of the underlying disease in 92% (290/314) of cases. An erroneous preoperative diagnosis was corrected by laparoscopy in 18% (58/314) of cases. This implied a change of the therapeutic strategy in 9% (27/314). Seventy five per cent (234/314) of patients were exclusively treated by laparoscopy, 22% (68/314) by laparotomy and 3% (11/314) by laparoscopically assisted surgery. Mortality was 2.5% (8/314) and morbidity 9% (29/314). In conclusion, laparoscopy is a valuable diagnostic tool for the surgeon in the context of acute abdomen and is an interesting therapeutic alternative in selected cases. However, it requires extensive experience in laparoscopic techniques. PMID- 7864540 TI - [Celioscopic treatment of inguinal hernias by intraperitoneal patch of ePTFE according to Spaw. Preliminary results of a prospective study of 162 hernioplasties in 135 patients. Groupe CHIC (Cure des hernies inquinocrurales sous coelioscopie)]. AB - Spaw's (original and modified) was technique evaluated in a prospective, multicentre study: from november 1992 to september 1993, 162 intraperitoneal laparoscopic herniorraphies were carried out in 135 patients for recurrent hernias or for hernias associated with a high risk of recurrence. Three needed an open procedure. Three early complications (2 periprosthetic hematomas, 1 microscopic bladder injury) were treated by another laparoscopy; a bowel loop retained in a trocar orifice was reintegrated under local anesthesia; dysesthesias of the lateral cutaneous nerve of the thigh in 1 patient and nonspecific parietal pain in 2 patients resolved within three weeks. Three seromas resolved after only one percutaneous aspiration. The mean post operative pain, evaluated by a visual analogic scale graduated from 1 to 10 was 1.8 (0 to 6) at D1, 05 (0 to 2) at D2 and the mean duration of analgesic requirments was 1.7 (0 to 15) days. The mean hospital stay was 2 (1 to 17) days for unilateral herniorraphies and the mean time to return to work or normal activity was 10 (2 to 44) days, even in heavy workers (35 patients). All patients were reviewed. The mean follow-up was 4 (1 to 10) months. Two complications needed further laparoscopic treatment: 1 recurrence at the internal edge of the patch, easily restapled with a stronger stapler, 1 bowel adhesion between patch and bladder revealed by pain without obstruction. The recurrence rate was 0.6% (1/162). The conversion rate was 2% (3/162) and the overall morbidity was 7.5% (12/162), decreasing respectively to 0 and 4% after the learning curve. This study confirms that Spaw's technique and its variant are feasible, and allows us to continue this study, and suggest these techniques would be useful in the treatment of some recurrent inguinal hernias. PMID- 7864541 TI - [Complications of laparoscopic cholecystectomy. Free intraperitoneal calculi]. AB - With the use of laparoscopic cholecystectomy, increasing numbers of gallstones are being left in the peritoneal cavity. To our knowledge, the rarely cause complications. We present two cases with stone spillage after laparoscopic cholecystectomy, with a different outcome. PMID- 7864542 TI - [Can injured biliary ducts be ligated for repair after dilatation? Apropos of 3 cases]. PMID- 7864543 TI - [Long-term results of surgical treatment of early cancers of the stomach]. AB - The postoperative course of 172 patients with early gastric cancer operated between 1974 and 1987 was reviewed with a median follow-up of 7 years. The survival probability at the end of 1989 was 0.916 (excluding operative mortality and other causes of death) or 0.876 when the operative mortality was included. Univariate analysis showed a significant survival difference according to the presence or absence of submucosal invasion (p = 0.02, Log-Rank test) and lymph node invasion (p = 0.04, age greater than or less than 50 years (p = 0.03) and according to the type of resection performed (total gastrectomy with gastric and perigastric lymph node dissection or subtotal gastrectomy with incomplete lymph node dissection (p = 0.05). Eleven patients died from cancer recurrence, one is still alive with a recurrence of the gastric stump. The other deaths were due to cancers of other organs (6), cardiovascular disease (2), pneumonia (3), septicaemia (1) and a car accident. Although the prognosis of early gastric cancer is relatively favourable in European countries, patients must be carefully followed for a long period because of recurrences and the high incidence of cancers in other organs. PMID- 7864544 TI - [Resection of necrotic tissue and prolonged peritoneal irrigation in the treatment of pancreatic abscesses]. PMID- 7864545 TI - [Carcinoma of the gallbladder: a 10-year experience in Chile]]. PMID- 7864546 TI - [Partial splenectomy for hematological indication. Apropos of 40 cases]. PMID- 7864547 TI - [Management of hypertensive patients while searching for a "thread of Ariadne" in the labyrinth of recommendations]. AB - The abundance of "recommendations" concerning the management of hypertension reflects the Public Health importance of this problem. This abundance and the absence of any real consensus concerning all aspects of this management can leave readers somewhat disconcerted. In this context, the authors attempt to define the guidelines adopted by the various Expert Committees in their approach in order to improve diagnostic performance and treatments, which are still very insufficient, in the field of hypertension. PMID- 7864548 TI - [Method of evaluation of relaxation and diastolic function]. AB - Impairment of relaxation and diastole is usual if not constant in cardiomyopathies and accompanies a disorder of cardiac contractile function. Certain heart diseases, especially hypertrophic cardiomyopathy, are associated with relative preservation of contractility and the predominant disorder concerns left ventricular filling. The clinical consequence of this impairment is dyspnoea due to elevated pressures of the left-sided cavities. The loss of atrial systole atrial is usually very poorly tolerated. There is an ambiguity of definitions, as, for the clinician, diastole starts at the time of closure of the aortic valve and consists of four phases: isometric relaxation, rapid ventricular filling, diastasis and atrial systole. In reality, this definition must be reviewed in physiological terms, asthe relaxation which allows the ventricle to return to its initial precontraction configuration is an active phenomenon which is actually part of ventricular systole. The reference methods of investigation remain haemodynamic methods with invasive measurements of left ventricular pressures and volumes. Myocardial isotope scan and especially echocardiography allow assessment of relaxation and diastole, although certain limitations of interpretation must be kept in mind. In terms of treatment, the demonstration of impairment of relaxation and diastole may require a different approach when contractile function is preserved. Calcium channel blockers could be useful and the preservation of atrial systole is always decisive. PMID- 7864549 TI - [Cardiac pacing in obstructive hypertrophic cardiomyopathies]. AB - Up until recently, the first-line treatment of obstructive hypertrophic cardiomyopathy was pharmacological and surgical in refractory cases. However, the immediate beneficial effect of a cardiac pacing on infra-aortic obstruction has been known for many years. The development of sophisticated two-chamber pacemakers and their use in patients with obstructive hypertrophic cardiomyopathy has confirmed their beneficial effect both in terms of haemodynamic and clinical parameters. There appears to be many reasons for this advantageous effect and only some of them have been elucidated, including alteration of the activation sequence of the left ventricle secondary to apical ectopic electrical activation and reduction of the contact time of the mitral valve with the proximal septum and, in the long term, ventricular remodelling secondary to release of the outflow obstruction. The increasing number of publications reporting a beneficial effect of two-chamber pacemakers in these patients justifies consideration of this approach in all patients refractory to drug therapy. PMID- 7864550 TI - [Can irreversible ventricular dysfunction be identified in patients with heart valve disease?]. AB - Cardiologists and heart surgeons are often faced with the problem of the optimal therapeutic indication in patients with valvular heart disease presenting with severe myocardial dysfunction, as it is difficult to evaluate the degree of reversibility of a severe alteration of ventricular function in these patients. Myocardial dysfunction is often multifactorial in patients with valvular heart disease and the role of myocardial ischaemia secondary to associated coronary heart disease must not be neglected. On the other hand, the compensatory capacity of the myocardium varies from one patient to another ("constitutional" myocardial factor or related to the aetiology of the valvular heart disease?). Although the methods of investigation of myocardial function currently available are able to precisely evaluate the degree of severity of myocardial dysfunction, they are unable to accurately predict the degree of reversibility. 1. In pure mitral stenosis, severe left ventricular dysfunction is very rare; more or less rapidly, pulmonary hypertension induces slowly progressive right ventricular dysfunction which remains reversible for a long time. 2. In mitral incompetence, left ventricular systolic function is correctly evaluated by the ejection fraction (LVEF). There is a high risk of irreversible left ventricular dysfunction in operated patients with an LVEF of less than 0.40. In these patients, left ventricular function is slightly improved after mitral repair, while LVEF decreases after mitral valve replacement. The combined study of right ventricular systolic function is useful in patients with mitral disease, as this function may be insidiously altered and the presence of right heart failure, regardless of its cause, considerably increases the late postoperative mortality of mitral valve disease. 3. In aortic stenosis, left ventricular dysfunction, hypertrophy and interstitial fibrosis remain reversible for a long time. Severe alteration of LV function therefore does not exclude the possibility of very good postoperative recovery. However, this is improbable in the presence of: a very marked increase in LV mass and/or end-systolic volume, and/or inoperable associated coronary artery disease, and/or the combination of low ejection fraction, severely decreased cardiac output, and low transvalvular gradient (not increased by cautious dobutamine infusion), and/or clinical signs of complete heart failure. 4. In aortic incompetence, progressive alteration of left ventricular function, often asymptomatic, is reflected by the increased dimensions of the LV and a reduction of the fraction of ejection. The reversibility of LV dysfunction is difficult for evaluate. The long clinical course of this dysfunction is one of the most reliable predictors of irreversibility, together with a fall in the resting isotope LVEF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864551 TI - [Characteristics of patients with coronary disease and aspirin prescription in Haute-Garonne]. AB - The MONICA Haute-Garonne Centre studied the incidence of myocardial infarction and death from coronary heart disease in 1,762 cases between 1985 and 1989. Changes in treatment were analysed in the subgroup of 416 patients admitted to hospital for myocardial infarction in 1986 and in 1989. The incidence of myocardial infarction decreased in men from 218.4 to 183.9 per 100,000 inhabitants (p < 0.01) and decreased nonsignificantly in women from 19.3 to 23.2 per 100,000 inhabitants (NS). The decreased incidence of myocardial infarction in men was exclusively due to a decrease by one-third of the incidence of infarction in patients with diagnosed coronary heart disease. Although the community mortality remained stable, the hospital mortality decreased by one half in man between 1985 and 1989 (21% versus 10%, respectively, p < 0.001). Between 1986 and 1989, the prescription of acetylsalicylic acid during the acute phase increased threefold (26.4% versus 72.9%, p < 0.001) and increased fivefold when coprescribed with fibrinolytics. Similarly, the prescription of aspirin on discharge from hospital doubled (from 32.6% to 69.5%, p < 0.001). The dosage of aspirin decreased from 500 mg or more per day in 1986 to a daily dose of approximately 250 mg in 1989. Lysine acetylsalicylate was the form most widely prescribed. In this population, patients treated by antithrombotics (aspirin or fibrinolytics) had a more favourable prognosis than patients not receiving any of these treatments. The changes observed in this study population are in line with the published results of therapeutic trials on antithrombotics in the acute phase of myocardial infarction and in the postinfarction phase (GISSI2, ISIS2). PMID- 7864552 TI - [Course of the left ventricular mass in a population of 893 hypertensive patients. Effects of treatment with perindopril]. AB - Left ventricular hypertrophy is now recognized to be a major and independent risk factor of mortality and morbidity. Although all classes of antihypertensives are able to reduce left ventricular mass, two recent metaanalyses have shown that ACE inhibitors are the most effective. The antihypertensive efficacy of perindopril in man is accompanied with a significant improvement in the functional properties of large arteries and with a reduction of LVH. This study was designed to assess the course of left ventricular mass by echocardiography in a population of 893 hypertensive patients with moderate left ventricular hypertrophy, treated with perindopril for 3 months. A significant fall in blood pressure was observed by the 6th week. The morphological and functional echocardiographic parameters on a large population provided more valid statistical results than in a small series. The left ventricular cavity was found to undergo symmetrical remodelling, adapted to the new haemodynamic status. The reduction of the thickness of the wall was in line with the reduction of the size of the ventricular chamber, and left ventricular mass was reduced by 8% (p < 0.001). Systolic function was preserved and diastolic function was improved. In particular, the E/A ratio was increased by 8% (p < 0.001) and the duration of isometric relaxation was decreased by 11 ms (p < 0.02). This improvement of filling was confirmed by the reduction of the diameter of the left atrium by 0.2 mm (p < 0.001). This open study in 893 patients therefore confirmed that perindopril corrects LVH in hypertensive patients. PMID- 7864553 TI - [Tilt test in the etiological diagnosis of syncope unexplained by electrophysiological study]. AB - In order to determine the role of tilt testing in the aetiological diagnosis of syncope unexplained by electrophysiological investigation, the authors retrospectively studied the results of this test in 275 patients with a mean age of 64 +/- 16 years. These 275 patients were divided into two groups: group I: 43 patients with a mean age of 50 +/- 19 years presenting with vagal syncopes, group II: 232 patients with unexplained syncope, probably vagal: group IIa (120 patients, mean age: 67 +/- 15 years), sudden syncope: group IIb (112 patients, mean age: 67 +/- 13 years). The electrophysiological investigation was inconclusive in every case. In group II, 50% of tilt tests were positive (19% under basal conditions, 31% after isoproterenol), with 61% of positive tests in group IIa, including 31% on the basal test, and 38% of positive tests in group IIb, including 11% on the basal test. In group I, 84% of tests were positive (33% on the basal test, 51% after isoproterenol), indicating a sensitivity of the test of 84%. In 96 patients with a doubtful electrophysiological investigation, the tilt test was positive in 70% of cases, allowing specific treatment or a pacemaker to be avoided in the majority of cases. 84% of vasovagal syncopes were therefore confirmed by tilt testing; 50% of syncopes unexplained by electrophysiological investigation were demonstrated to be of vasovagal origin. The author emphasize the value of tilt testing in certain discordant situations in which the clinical context is disturbing and/or electrophysiological investigation is not completely reassuring. PMID- 7864554 TI - [Non-calcified chronic constrictive pericarditis. Diagnostic difficulties and contribution of complementary tests]. AB - The authors report a case of noncalcified chronic constrictive pericarditis, in which the diagnosis was delayed due to an associated mitral stenosis. The diagnostic value of various invasive and noninvasive complementary investigations is discussed. PMID- 7864555 TI - [What is the appropriate treatment for myocardial infarction with left ventricular dysfunction?]. AB - The essential goal of medical treatment following myocardial infarction with left ventricular dysfunction must be the prevention of secondary cardiac failure. The existence of left ventricular dysfunction, in particular when it is not accompanied by clinical cardiac failure, is a virtually formal indication for beta-blocker treatment after an infarction. Beta-blockers with intrinsic sympathomimetic activity (ISA) are possibly better tolerated in this context. However, experience shows that cardiologists and general practitioners often remain reluctant to prescribe beta-blockers whenever left ventricular function is impaired. Converting enzyme inhibitors decrease the risk of onset of secondary cardiac failure, reduce sudden deaths by ventricular arrhythmias, reduce recurrences of myocardial infarction or unstable coronary insufficiency, and more generally reduce overall and cardiovascular mortality. This is a class effect. While there is no urgency to prescribe them during the acute phase, it is generally considered that it is extremely useful to give them fairly quickly, i.e. during the first 72 hours. At the end of the hospital phase, around two weeks, it is desirable, whenever possible, to prescribe a dose of the order of 75 mg/day of captopril or 2.5 mg/day of ramipril. The administration of aspirin can be considered virtually routine. Oral anticoagulants are desirable in the presence of a large akinetic pocket, a frequent starting point of thrombosis and/or systemic emboli, or in the presence of atrial fibrillation. Digitalis/diuretic treatment does not appear to be indicated at this stage. Other types of anti-ischemic treatment are not theoretically indicated as a matter of principle at this stage in the absence of residual ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864556 TI - [Should all cases of aortic valve stenosis be surgically treated?]. AB - Aortic stenosis is a condition in which progression accelerates with the onset of warning symptoms such as angina pectoris, syncope and heart failure. Surgery must be scheduled as quickly as possible in all such symptomatic patients, even in the presence of concomitant coronary disease, or of left ventricular failure. Aortic valve surgery is possible in the elderly, with a higher operative risk, but with the benefit of a symptomatic improvement identical to that seen in younger individuals, and a prolongation of life expectancy. Surgery is often considered in asymptomatic patients because of the fear of sudden death. In actual fact, sudden death not preceded by other symptoms is rare and the aim of surveillance must be to identify high-risk patients to whom surgery may be offered: poor exercise tolerance in a cautiously administered exercise test, abnormal ventricular function by echocardiography, or the existence of arrhythmias, which are also a severity factor, whether atrial or ventricular. The number of completely asymptomatic cases among patients with tight aortic stenosis is relatively slight, having been evaluated at 5%. It is in these asymptomatic patients, when they are young, that it is possible to delay surgery until the onset of a first symptom. PMID- 7864557 TI - [Telephone transmission of electrocardiograms. A link between outpatients and hospitals]. PMID- 7864558 TI - [Results of endarterectomy combined with angioplasty in aortocoronary bypass]. AB - From January 1989 until April 1990, 472 consecutive patients were operated for coronary artery bypass grafting. The patients were classified into three different groups. In group I, 412 patients were operated without endarterectomy. Group II consisted of 37 cases operated with endarterectomy-bypass to 41 vessels. Group III consisted of 23 cases of endarterectomy combined with patch plastybypass to 24 vessels. The length of the segment endarterectomized was 25 to 70 mm (mean 37.86 +/- 12.18 mm). Peri-operative myocardial infarction occurred in 19 cases in group I (4.61%), 6 cases in group II (16.21%), and 3 cases in group III (13.04%). The percentage of IABP utilization was 2.91% in group I; 10.81% in group II; 8.69% in group III. The hospital mortality for group I, group II and group III was 3.88%; 8.10% and 8.69%. Mean follow-up was 16.4 months for 72% of patients. In 5 cases of group I (1.80%), in 8 cases of group II (27.58%) and in one case of group III (5.55%), myocardial infarction occurred in the late post operative period. Late mortality was 1.44% for group I; 17.24% for group II and 5.55% for group III. There was no statistically significant difference between groups II and III, but the late results of group III are probably better. PMID- 7864559 TI - [Reoperation for heart valve prosthesis. Apropos of 99 cases]. AB - From March 1977 to November 1988, 99 patients were reoperated on after a first valvular replacement. Mean delay between the two operations was 53 months (10 days to 18 years). The patients were reoperated on mainly for mechanical disinsertion (30), bacterial endocarditis (25) and thrombosis (18 patients). Operative mortality was 11%, mainly following reoperation for bacterial endocarditis. Mean follow-up (85 patients) was 49 months (6 months-11 years). 75% were alive and doing well 4 years after reoperation and 66% at 6 years. Eight patients needed a third operation with two deaths. PMID- 7864560 TI - [Video-assisted pulmonary excision surgery. Technique, indications and initial results]. AB - Video-assisted thoracic surgery (VATS) is a compromise between conventional thoracic surgery performed via a thoracotomy of variable dimensions and surgical videothoracoscopy, which, using only small operating channels, requires the use of specific instruments, gives a field of vision exclusively by video camera and raises the delicate problem of extraction of the resection specimen. VATS is performed via a minithoracotomy, 3.5 to 5 cm long, using a video camera. In this way, the operator has two forms of vision throughout the operation: direct vision through the orifice of the minithoracotomy and visualization of the video screen. This technique also allows extraction of the resection specimen at the end of the operation. Between February and May 1993, 20 patients (14 males and 6 females with a mean age of 56 years) underwent lung resection by VATS (18 lobectomies and 2 pneumonectomies). Eighty-eight patients had a malignant tumour and 2 had a benign disease. Lymph node dissection was routinely performed in patients with a malignant lesion. The mean size of the tumours was 3.2 cm. The operative mortality was nil. The mean operating time was 154 minutes. The postoperative course was uneventful in 14 patients, but two cases of atelectasis on DO, one bronchial infection and one chylothorax, treated medically, were observed. The authors report the current criteria of their indications as the feasibility and reliability of this new technique. Results on pain and patient comfort, postoperative analgesia requirements, recovery of respiratory function and possible long-term sequelae remain to be demonstrated, which is the objective of a current prospective study. PMID- 7864561 TI - [Evaluation of the analgesic effect of naftidrofuryl in permanent ischemia in patients with arterial diseases. Double-blind versus placebo study]. AB - Ischemic rest pain, with or without trophic disorders and occurring very frequently at night, is responsible for insomnia and complications such as positional oedema. The pathophysiological mechanisms underlying the analgesic effect of naftidrofuryl led us to evaluate the efficacy of this treatment. 37 selected patients were given 2 daily infusions of 400 mg of naftidrofuryl for 8 days, under double-blind conditions. Evaluation criteria were pain assessment using a visual analogue scale, analgesic consumption considering both the power (WHO scale: level I paracetamol, level II dextropropoxyphene, level III morphine) and the dosage of the analgesic used (analgesic score), index of therapeutic success including the level of pain reduction and the absence of analgesic use. The results showed a significant difference in favour of naftidrofuryl for: reduction of pain, difference in the course of the analgesic score, the distribution of the population according to the index of therapeutic success. Three patients discontinued treatment due to inefficacy, but all 3 belonged to the placebo group. This study demonstrates the benefit of naftidrofuryl in pain reduction which was assessed, in particular, by the reduction of analgesic consumption. PMID- 7864562 TI - [Urethroplasty using polyglactin mesh in urethral fistula caused by decubitus ulcer of the perineum in spinal cord injuries. Apropos of 7 cases]. AB - Seven paraplegic patients, presenting with urethro-cutaneous fistulae due to a loss 4 to 10 cm of urethral tissue, due to decubitus ulcer of the anterior perineum, were cured. Urethroplasty was performed by wrapping the urinary catheter in a resorbable polyglactin net, covered on top by a flap of a well vascularized musculocutaneous biceps femoralis flap. The follow-up of several years proved the reliability of this technique which can be perfectly applied to others kinds of urethroplasty. PMID- 7864563 TI - [Fascia superficialis temporalis in facial reconstructive surgery. Apropos of 35 cases]. AB - The fascia superficialis temporalis (FST), one of the planes of cranial cover, can be raised to form an axial pedicle flap or a vascular island flap on superficial temporal vessels. Its fibrovascular structure, the area able to be raised and the possible addition of other superficial tissues (scalp, forehead skin) and deep tissues (calvarial bone) mean that this flap can be used in surgery of the external and intracavitary facial contours and shapes. The authors report their experience of 35 facial reconstructions: 7 ear reconstructions, 5 suspensions of a paralysed labial commissure, 10 conjuctivo-palpebral revisions, repair of 5 subcutaneous defects, 3 haired resurfacings, 1 inferior labial, 1 cheela, 1 orbitomalar reconstruction, 1 malo-commissuro-labial repair, 1 prefabricated free flap. The donor site sequelae were considered to be negligible: 1 case of temporal anaesthesia with dysaesthesiae, 4 cases of band alopecia. The analysis of these 35 reconstructions reveals the quality of all cases of defect repair, especially palpebral; the ease and persistence of suspensions of the labial commissure; the value of FST as a conjunctival and buccal mucosal substitute; the density of the hair contribution. However, total or partial ear reconstruction using this technique constitutes a more limited indication. PMID- 7864564 TI - [Facial paralysis. Treatment of upper eyelid occlusion by inclusion of a concealed gold plate]. AB - Inclusion of a gold plate to oppose the action of the levator muscle has been proposed for a long time in the treatment of superior palpebral paralysis. Long term ulceration of the overlying skin has generally led to the abandonment of this technique. The simultaneous insertion, in front of the gold plate, of a conchal cartilage graft, which is subsequently reinhabited, overcomes this disadvantage. This is a simple, rapid, reversible, effective procedure which is indicated essentially in longstanding or recent permanent facial paralysis, but also as temporary treatment while waiting for the results of suture, graft or anastomosis of the facial nerve. PMID- 7864565 TI - [Use of autologous fibrin glue in facial reconstruction by total skin graft]. AB - Fibrin glue of human origin was used in 12 patients following excision of facial skin tumors and reconstruction skin graft. Positive results were achieved in all cases with good by full-thickness healing, reduction of operating time and good aesthetic results. PMID- 7864566 TI - [Iliac transosseous transposition of rectus abdominis muscle flap to cover a sacral pressure sore]. AB - The use of an inferiorly based rectus abdominis myocutaneous flap to cover a pelvic pressure sore offers a solution when the possibilities of other local flaps have been exhausted. For sacral pressure sores, the iliac bone is an obstacle for the transposition of this flap. In this case report, we describe how this obstacle can be overcome by creating a trans-osseous tunnel in the ala of the iliac bone through which the flap takes the most direct route to the recepient site. PMID- 7864567 TI - [Flexible penile implants. An experience over 60 cases]. AB - The author proposes flexible silicone elastomer penile prostheses or implants to restore erectile function. They have the advantage of being flexible, adjustable during the operation and they can be elongated by traction and are resistant to axial pressure. The surgical incisions are explained, in particular the penopubic approach, together with insertion of the implants accompanied by cavernopublic disinsertion and recentering of the glans in patients with La Peyronie's disease. Sixty patients were operated and reviewed with a follow-up of 8 months to 4 years. There were no cases of infection of rejection. 85% of patients were satisfied with the quality of their erectile function. The haemodynamic mechanisms of impotence, situated either in the corpora cavernosa or in the peripheral venous plexus, are reviewed. Flexible penile implants allow restoration of erectile function via various combinations of three possible mechanisms: reduction of the free cavernosal volume, increased resistance to venous drainage, and increased intracavernosal pressure. PMID- 7864568 TI - [Colpoplasty for vaginal aplasia by rectovesical dissection and thin skin graft with adjustable stent. Review of the literature apropos of 4 cases of surgically treated Mayer-Rokitansky-Kuster-Hauser syndrome]. AB - The congenital absence of the vagina has a low incidency but it is a very invalidating condition. The Mayer-Rokitansky-Kuster-Hauser syndrome represents 90% of all cases of vaginal aplasia. The authors review the anatomical classification, etiopathogenesis, epidemiology, diagnosis and treatment. Between 1981 and 1991, four cases were treated by recto-vesical dissection and split thickness skin graft technique with adjustable stent. The results are good and correspond to those of the literature. Their quality and duration depend on maintaining the stent for a sufficient length of time. Frequent post-operative follow-up is necessary to prevent graft retraction and to give psychological support when it is needed. PMID- 7864569 TI - [Vaginal reconstruction by musculocutaneous flap of the rectus abdominis after pelvic cancer surgery. Apropos of 11 cases]. AB - Surgical treatment of gynecological neoplasms leads to two problems: pelvic defect, and vaginal reconstruction. The authors have been using rectus abdominis musculo-cutaneous flap as described by Tobin. Eleven patients have been treated. A horizontal flap was used in one patient and a vertical one for the 10 other patients. The authors had one failure. In the ten other patients the average healing time was 21 days and 5 patients were able to return to sexual activities. The use of rectus abdominis flap would appear to be an easy and reliable technique for pelvic reconstruction. PMID- 7864570 TI - [Transsexualism: surgical aspects. An experience of the plastic surgical unit's in Bordeaux]. AB - After briefly reviewing the history of transsexual surgery, the authors explain their technical choices and present their experience based on a series of 19 patients, 11 male transsexuals and 8 female transsexuals. The results are analysed. The potential complications of surgery in female transsexuals are those of microsurgical techniques aggravated by treatment with testosterone, as well as urethral fistulae and strictures. In addition to prevention of thromboses, the authors palliate these complications by ulnar elongation of the radial forearm flap in order to minimise the factors responsible for urethral fistulae, combined with enlargement of this flap to decrease the risk of stricture. The complications in male transsexuals essentially consist of rectoneovaginal fistulae. Problems of the depth of the neovagina are also important. Two rectoneovaginal fistulae were observed in this series of 11 patients, both treated medically. The unit's experience in this field will be continued in order to further improve the results. PMID- 7864571 TI - [It was yesterday: the difficulty of sex determination because of errors of nature]. PMID- 7864572 TI - [Apropos of 49 transverse rectus abdominis muscle flap (TRAM) in carcinologic and reconstructive surgery]. AB - The C.A.C. de Nice reconstructive surgery unit presents their experience of TRAM pedicled flap (41 cases) or free flap (8 cases). The technical details, complications and sequelae are analysed for the entire series of flaps with particular attention to the problems of the abdominal wall and the respective advantages of the two techniques. The applications of TRAM essentially concern breast reconstruction (41 cases) in women with large breasts and not desiring an implant or a contralateral procedure. TRAM is compared to other procedures (latissimus dorsi, implant, greater omentum) which the authors consider to be valid alternatives. The other indications are reconstructive, either for the chest wall (5 cases) or inguinoperineal (3 cases) for defects in an irradiated region. PMID- 7864573 TI - [Analysis of 156 breast reconstructions by transverse rectus abdominis muscle flap (TRAM)]. AB - The myocutaneous rectus abdominis flap described by Hartrampf was used for 156 breast reconstructions between 1982 and 1992. 107 reconstructions were done with one pedicle. 142 were delayed reconstructions. Partial necrosis of the flap occurred in 10% of the cases in bipedicled flaps and 20% in unilateral flaps. No hernia occurred in this series. Cosmetic results are considered satisfactory or very satisfactory in 59% of the cases when evaluated by the medical team and 76.5% when evaluated by the patients. As a conclusion of this study, the TRAM flap is preferred in delayed reconstructions when local and general conditions are suitable, rather than latissimus dorsi flap reconstructions which require an implant. PMID- 7864574 TI - [Reconstruction of the lower abdominal wall after extensive full-thickness excision]. AB - The reconstruction of major inferior abdominal wall defects is a rare but difficult problem. We present five consecutive cases of reconstruction following major excision for the treatment of tumors (3 cases) and radionecrosis (2 cases). The immediate reconstruction was performed by fasciomyocutaneous flaps of the thigh, pedicled on the tensor fascia lata (4 cases) or the rectus femoris (1 case). The functional results of the abdominal reconstruction are good. The sequelae of the donor site are mainly aesthetic; the function of the thigh is not affected by the harvest. These two flaps are very reliable. The rectus femoris flap has muscle throughout the extent of the flap and may be preferred in contaminated wounds or postradiation ulcers. It also allows the midline to be reached more easily. PMID- 7864575 TI - [Surgical classification of androgenetic baldness and its therapeutic implications]. AB - In order to understand the various operative indications in baldness surgery, we describe a dynamic classification of baldness with practical implications. The most predictive factors of this classification are scalp laxity and the height of the crown. PMID- 7864576 TI - [Sertoli cells. Functional aspects compared in rats, pigs and man]. AB - In the mammalian testis, the Sertoli cell plays a key role in the development and maintenance of spermatogenesis. Indeed, within the seminiferous tubule, the structure of the Sertoli cells and the specialized junctions between them and the neighbouring germ cells, contribute to create the sophisticated microenvironment and to bring all the nutriments require for a full development of germ cells. In this review, we have compared the main Sertoli cell functions in the rat and the pig to the available data concerning the human. We have included our recent results obtained from testicular tissues of 15 young men (mean age: 29 years) from which we have prepared the Sertoli cells. In addition to the lactate and estradiol-17 beta syntheses, the human Sertoli cell produces several proteins, namely transferrin, ferritin and inhibin under the control of germ cells. PMID- 7864577 TI - [Corticotropin-releasing factor and anorexia nervosa: reactions of the hypothalamus-pituitary-adrenal axis to neurotropic stress]. AB - The aim of this study is to obtain CRF (Corticotropin Releasing Factor) stimulation at a suprahypothalamic level with a psychological stressor and to evaluate its response in anorexia nervosa. CRF plays a major role in the mechanisms underlying the hypothalamo-pituitary-adrenal (HPA) system's response to stress. Animal studies clearly showed that CRF is involved both in the adaptation to a novel environment and the regulation of eating behaviour. CRF's staietogenic effect is mediated via the paraventricular nucleus. Three groups of age matched young women were studied: 8 patients meeting the DSM III-R criteria for anorexia nervosa, 8 underweight healthy volunteers and 10 normal weight volunteers. All subjects were submitted to an auditory stimulation test ("psychosocial stress test") consisting of an intellectual task in which maximal performance is impossible to achieve, the subjects being permanently disturbed by various meaningful noises. Subjects were asked to answer self-rating scales for anxiety and tension prior to and after the test. CRF reactivity was measured by salivary cortisol (RIA). After the test, anorexia nervosa patients exhibit a significantly higher salivary cortisol response compared to the normal weight volunteers. In most of cases, salivary cortisol response was not correlated with the psychological variables. The range of the response is very explosive in two anorectic patients. Our data are consistent with the hyperactivity of the corticotropic axis stress response in anorexia nervosa, but request further investigations to prove that. PMID- 7864578 TI - [Drug modulation of libido and sexual activity. Behavior effect of GnRH analog in man]. AB - Libido and male sexual behaviour are under the control of complex testosterone dependent neuro-endocrine mechanisms. Better knowledge of these mechanisms has allowed to modulate sexual behaviour using drugs. Indeed, it is possible to block spontaneously uncontrollable sexual pulsions of aggressive hypersexual men by dropping testosterone secretion and consecutively decreasing androgen effects on target cells. From now, mutilating neurosurgery and treatment with either estrogens or antigonadotrophic progestagens are withdrawn. Cyproterone acetate, acting as a competitive inhibitor of testosterone action through its binding to androgen receptors, has been used with efficacy in 80% of cases studied. However, the therapeutic use of cyproterone acetate is limited by three drawbacks: i/potential side effects, ii/exclusive oral route of administration and iii/lack of available biological criteria as a control of the good observance of the treatment. We studied the efficacy of a GnRH analogue (Triptoreline), which induces a reversible hormonal castration and of which both the formulation and the route of administration avoid the inconveniences linked to a treatment with cyproterone acetate. 3.75 mg triptoreline injected intramuscularly once a month had been very effective on clinical and biological parameters in 5/6 aggressive hypersexual patients. In 3 of them a previous treatment with cyproterone acetate had been uneffective. Such a reversible hormonal castration suppressing sexual addiction, would lead to favourable conditions for psychotherapy. PMID- 7864579 TI - Luteinizing hormone-releasing hormone (LHRH) and neural cell adhesion molecule (NCAM)-immunoreactivity in development of the forebrain and reproductive system. AB - The origin and migration of LHRH neurons (detected by immunocytochemical procedures) is preceded by a migration of NCAM-immunoreactive cells from the olfactory epithelium, and the formation of an NCAM-immunoreactive cellular aggregate between the olfactory epithelium and the developing forebrain. The central processes of the olfactory nerves grow into the lateral parts of this aggregate and the terminal and vomeronasal nerves grow into the medial parts. No nerve fibers of the main or accessory olfactory systems grow directly into the forebrain. The LHRH neurons, following the course of the terminal and vomeronasal nerves, traverse the medial edge of the NCAM-immunoreactive cellular aggregate before they enter the medial forebrain caudal to the developing olfactory bulbs. The LHRH neurons do not migrate through the olfactory bulbs. After formation of the olfactory bulbs, the cellular aggregate disappears and is replaced by the olfactory nerve layer of the olfactory bulb. The NCAM and LHRH-immunoreactive cells on the medial side appear to the retained in the ganglion terminale of the terminal nerve. The fate of the NCAM-immunoreactive cells that formed the aggregate could not be determined by the methods used in these studies. The early appearing NCAM-immunoreactive cells may function to separate and direct axons of the olfactory, vomeronasal and terminal nerves (and the LHRH neurons) to their respective targets in the forebrain. The development and migration of neurons from both the lateral and medial parts of the olfactory placode appears to be essential for the normal development of the forebrain and reproductive system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864580 TI - Somatostatin and pituitary adenylate cyclase-activating polypeptide (PACAP): two neuropeptides potentially involved in the development of the rat cerebellum. AB - Somatostatin and pituitary adenylate cyclase-activating polypeptide (PACAP) have been originally isolated from the ovine hypothalamus on the basis of their hypophysiotropic activities. There is now evidence that somatostatin and PACAP may play a role in the development of the central nervous system, particularly in the cerebellum. High concentrations of somatostatin and somatostatin receptors have been detected in the rat cerebellum during the first two postnatal weeks. Somatostatin binding sites are associated with a germinative matrix, the external granule cell layer, which generates the majority of the interneurons of the cerebellum. By using immature granule cells in primary culture, we could demonstrate that somatostatin binding sites are actually expressed by neuroblasts and correspond to authentic receptors negatively coupled to adenylate cyclase. Concurrently, studies on the distribution of PACAP receptors in the immature rat cerebellum showed the presence of a high concentration of binding sites in the external granule cell layer during the first two postnatal weeks. Pharmacological characterization of these binding sites showed that they correspond to type I PACAP receptors positively coupled to adenylate cyclase. The concomitant and transient expression of somatostatin and PACAP receptors by cerebellar neuroblasts in the external granule cell layer suggests that the two neuropeptides may be involved in the regulation of multiplication, migration and/or differentiation of neuroblasts. This hypothesis is also supported by the actions of somatostatin and PACAP on various transduction systems. In particular, the opposite effects of the two neuropeptides on adenylate cyclase activity suggest that somatostatin and PACAP may exert antagonistic actions. PMID- 7864581 TI - GnRH neurons and other cell populations migrating from the olfactory neuroepithelium. AB - Cell migration from the olfactory neuroepithelium to the brain has been widely studied during vertebrate development. Immunocytochemical analysis has revealed that many of the migrating cells contain GnRH (Gonadotropin-Releasing Hormone). The GnRH positive cells migrate from the medial olfactory placode, steam along the nasal septum, cross the basal forebrain and reach the hypothalamic and septal areas from where they control the release of hypophyseal gonadotropic peptides. A peculiar feature of these cells is that they start expressing GnRH during migration. We have analysed the presence of immunoreactivity for peptides typically expressed in olfactory neurones, along the migratory pathway followed by GnRH neurones. We have used polyclonal antibodies raised against carnosine and olfactory marker protein (OMP), and performed double immunolabelling on mouse embryos and on early neonatal Brazilian opossum (Monodelphis domestica) tissues. Beside the GnRH neurones we observed other migrating cells along the pathway traced by olfactory terminal and vomeronasal nerves. Most of these cells co express carnosine and OMP. The carnosine/OMP migrating cells are detectable in later developmental stages than GnRH neurones. GnRH neurones do not express either OMP or carnosine. By keeping in culture explants of the brain together with the olfactory region from newborn opossums, we have shown that it is possible to obtain the migration of the different populations in vitro. Moreover the GnRH cells are co-distributed, but different from those expressing olfactory markers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864582 TI - Ontogeny of the sensitivity of the somatotrophes to thyrotrophin releasing hormone (TRH) and growth hormone releasing factor (GRF) in the embryonic and posthatch chick. AB - The ontogeny of the in vitro growth hormone (GH) release after stimulation with thyrotrophin releasing hormone (TRH) or growth hormone releasing factor (GRF) has been studied in two strains of chickens during the last week of embryonic development and the first week posthatch. Fourteen-day-old embryos did not yet respond to any of the stimuli applied, while the amplitude of the GH response to the different stimuli increased gradually from 18-day-old embryos to 1-day-old chicks. The evolution of the responses to both stimulating agents was parallel in the two strains of chickens, but the amplitude of the response was always higher in the rapidly growing broiler strain compared to the slowly growing layer strain. The highest GH response was at all stages obtained with the highest dose of GRF (100 nM). At a lower dose (10 nM), however, TRH seemed to be a more effective GH releasing agent than GRF at the posthatch stages. PMID- 7864583 TI - [Treatment of acromegaly with a new slow release somatostatin analog, lanreotide]. AB - Treatment of Acromegaly has been improved by the development of the somatostatin analogs characterized by an increased specificity and longer duration of action. One of these analogs-Lanreotide- (Somatuline) is supplied under a slow release formulation and does not require several daily injections like other analogs presently available. The clinical pharmacodynamic studies that have been conducted in healthy and acromegalic patients show that the i.m. injection of a single dose of this slow-release formulation leads to a significant decrease of the plasma GH and IGF-1 levels. This effect lasts at least 14 days. The Lanreotide slow-release formulation has been used to treat 123 acromegalic patients who presented with a still evolutive disease after conventional therapy. The product was given at a 30 mg-dose every 10 or 14 days during a 3-to 24-month period. This treatment led to a reduction of the symptoms and to a decrease of GH hypersecretion. GH and IGF-1 levels have been normalized respectively in 46% and 32% of the patients. The observed results allow to conclude to an immediate efficacy of the treatment (without escape sign). The adverse drug events are minor and transitory. The antitumor effects are modest and inconstant. The slow release formulation seems to provide the patients with a better quality of life, as compared to the several daily injections. PMID- 7864584 TI - [11 beta-Hydroxysteroid dehydrogenase (11-beta-OHSD): physiology and lack of action in pathology]. AB - The 11 beta OHSD is an ubiquitous enzyme which inactivates cortisol to cortisone by transforming the hydroxyl group at the 11-carbon to a keto group. Therefore, it confers to mineralocorticoid receptors their selectivity toward their ligand and may constitute an important mechanism of regulation tissue-specific of the access of ligand toward its receptors. More widely the 11 beta OHSD would modulate glucocorticoid activity to their own receptor. There is no possibility to measure directly this enzyme and its deficiency is indirectly evaluated by enhancement of the quotient (THF + alpha THF)/THE after analysis of urinary steroid metabolites. Such enzymatic deficits may be congenital and are observed in childhood where they give an apparent mineralocorticoid excess (AME) syndrome (type 1). Sometimes acquired and reversible, they are due to licorice intoxication, hypothyroidism, chronic alcoholism and may be involved in the genesis of some cases of hypertension. PMID- 7864585 TI - Release of a prolactin-like substance by bovine granulosa cells in vitro: effects of ovarian steroids. AB - The time-dependent accumulation of prolactin (PRL) immunoreactivity in serum-free and in serum-supplemented cultures of bovine granulosa cells was observed. Blockade of endogenous progesterone by specific antiserum had no significant influence on PRL immunoreactivity, but progesterone addition (10-10,000 ng/ml) lead to a dose-dependent decrease. Antisera against testosterone and against estradiol-17 beta were inhibitors, and additions of these hormones (100-10,000 ng/ml) stimulated the release of PRL immunoreactivity. The results obtained suggest the secretion of a PRL-like peptide by bovine ovarian cells. Growth hormone, testosterone and estradiol may be stimulators, and progesterone a possible inhibitor of this process. PMID- 7864586 TI - [Adrenal insufficiency and antiphospholipid syndrome]. AB - We report a case of acute adrenal insufficiency secondary to bilateral adrenal hemorrhage, in a 53 year old patient, occurring in the post-operative course of a lower limb ischemia. The patient was found to have a lupus anticoagulant, and it was concluded that the adrenal insufficiency was related to a primary antiphospholipid syndrome (PAPS). The PAPS is a cause of both, acute and chronic adrenal insufficiency. Endocrinologists are relatively little familiar with this etiology. Pathophysiologically, thrombosis and bilateral adrenal hemorrhage can result in progressive bilateral adrenal atrophy, requiring life long substitution. Therefore, the importance to search for antiphospholipid antibodies in the evaluation of acute and chronic adrenal insufficiency has to be emphasized. PMID- 7864587 TI - Evaluation of a transgenic mouse model for alpha-1-antitrypsin (AAT) related liver disease. AB - We have attempted to produce a transgenic mouse model of the neonatal liver disease associated with the human PIZ allele. Analysis of a number of transgenic mouse lines carrying either a normal human PIM gene construct or the mutant Z is reported. Using isoelectric focusing analysis of plasma from transgenic mice, we have shown that the human AAT proteins produced in mice are processed in a similar way to their counterparts in humans. By comparing the level of M and Z mRNA in liver with the levels of M and Z proteins in plasma we have inferred that, as in humans, the mutant protein tends to accumulate within the hepatocyte. Accumulation of Z protein has also been demonstrated by immunocytochemistry. Two of the M transgenic lines produce such high levels of the human protein that it, like the Z protein, accumulates as globules. Histological features of livers from 116 mice of different ages and genotypes were examined: 37 non-transgenic, 62 Z transgenic (23 low expressing and 39 high expressing) and 17 M transgenic mice, all high expressing. Cirrhosis or fibrosis was not seen in any animal and we were unable to find any evidence for neonatal liver disease. Some necrosis was seen in all genotypes and this increased significantly with age with one Z line showing significantly more frequent necrosis than any other group. This line, the highest expressing Z line, was back crossed onto 7 different genetic backgrounds but no major differences between the back crosses with respect to liver disease were observed. The mouse model we have developed is compared with other transgenic Z mouse models; none of these is representative of human neonatal liver disease. Our view is that the transgenic animals generated in these experiments may be most useful for investigating the liver manifestations that almost invariably occur in ZZ adults. Alteration of additional factors other than accumulation of Z protein, for example inactivation of the endogenous mouse genes or some environmental challenge, might produce a mouse model with more relevance to neonatal liver disease. PMID- 7864588 TI - Consanguineous marriage in Turkey and its impact on fertility and mortality. AB - Turkey has a high rate of consanguineous marriage (21.1%), indicating strong preference for this traditional form of marital union. Social and cultural factors are especially important in marriages between first and second cousins. Fertility is high, the closed birth interval is long, and the sterility rate is low among these couples. Post-neonatal, infant and under-5 mortalities are high in first cousin unions by comparison with non-consanguineous marriages. According to the results of the study, first cousin marriage is a significant determinant underlying the high total fertility and infant mortality rates in Turkey. PMID- 7864589 TI - Age of onset in familial adenomatous polyposis: heterogeneity within families and among APC mutations. AB - Heterogeneity among and within FAP pedigrees for the age of symptom onset and the age at death from colorectal cancer was studied in a sample of 583 patients of the Italian Polyposis Registry. The among pedigree variation was largely explained by clustering of families in two groups, 'early FAP' (most colorectal cancer deaths below 45 years of age) and 'late FAP' families (most deaths above age 45). The within-family variation was explained by a marked phenomenon of anticipation (15 years per generation, on the average), possibly not due to ascertainment bias. We then considered the pedigrees with identified mutation in the APC gene. Six families shared a common deletion at codon 1309 and showed the early FAP phenotype. Two families shared a mutation at codon 1061 and revealed the late FAP phenotype. Another two families (codons 453 and 302) clustered with the late FAP group, whereas a family with mutation at codon 835 clustered with the early FAP group. We suggest that there are at least two classes of mutations in the APC gene with different consequences at the phenotypic level. It seems that there are several critical points within the APC protein sequence at which truncation causes a more aggressive disease than truncation at other points. PMID- 7864590 TI - An algorithm for Monte Carlo estimation of genotype probabilities on complex pedigrees. AB - Exact probability and likelihood computation on complex pedigrees is often infeasible, since exact methods are too computationally intensive even with today's computing technology. A statistical tool, Markov chain Monte Carlo (MCMC), is increasingly being explored as a technique for estimating probabilities of genotypic configurations on pedigrees conditional on phenotypic data. However, this conditional probability distribution on a complex pedigree is, in general, multimodal, and multimodality is one of the major difficulties in MCMC exploration of a probability surface. In this paper, a new member of the MCMC Metropolis-Hastings class of algorithms is proposed; the heated-Metropolis algorithm. The algorithm achieves passage through low probability states to other local modes of the probability distribution, and so provides much improved estimates of probabilities of interest. The example considered is the estimation of the probabilities of carrier genotype for the founders of a complex pedigree in which a very rare lethal recessive trait is segregating. PMID- 7864591 TI - Genetic analysis of atopy and asthma as quantitative traits and ordered polychotomies. AB - Traits related to atopy and asthma were defined in a random cohort of 131 families with three or more children. Correlation analysis provides no evidence of imprinting, maternal effect, or a major role of environment shared by sibs. Commingling analysis favours more than one distribution, the upper one being common for asthma and very common for atopy. Segregation analysis of rank transformed variables provides only equivocal evidence of major genes against a polygenic background but suggests that such genes (if present) are individually common and not of large effect. Segregation analysis under a two-locus model gives consistent results with minimal distributional assumptions. To enter combined segregation analysis we favour a restricted model in which the major locus is additive on the liability scale and the pseudopolygenic modifier locus accounts for at least half the genetic variance. Total IgE and bronchial reactivity are proposed for meta-analysis of atopy and asthma respectively. Genetic analysis of complex inheritance is discussed and it is shown that allelic association with random loci is not a feasible approach. PMID- 7864592 TI - Genetic and environmental effects on coronary heart disease risk factors in northern Norway. The cardiovascular disease study in Finnmark. AB - This study comprised 1377 first degree relatives in 575 families ascertained through a comprehensive screening of the general population from 20 to 52 years of age. Path analysis using parsimonious models gave evidence of significant biologic and environmental transmission for total cholesterol (genetic and cultural heritabilities were 0.46 and 0.05, respectively), high density lipoprotein cholesterol (0.42, 0.10), triglycerides (0.21, 0.07), and systolic (0.48, 0.04) and diastolic (0.35, 0.05) blood pressure. Compared with other studies employing the same path analytic model, heritability estimates in general were among the highest reported, except for the somewhat lower genetic component in total cholesterol and triglycerides. For the first time in a single sample from the general population, lipid and blood pressure variables were investigated applying the same methodology, and good agreement was illustrated by the result that identical parsimonious models were reached for all phenotypes, with the exception of a single additional parameter for total cholesterol. About one fourth to one half of the total phenotypic variance could be ascribed to genetic sources, whereas the contribution from shared familial environment was much smaller. PMID- 7864593 TI - Disease susceptibility genes and the sib-pair method: a review of recent methodology. AB - There is now a considerable body of literature which describes and analyses various methods of testing for the presence of disease susceptibility genes by examining the degree of HLA haplotype sharing of parental haplotypes over random expectations amongst affected siblings. We here survey a number of improvements, generalizations and extensions of the earlier reported methods with the aim of bringing them to the attention of those who are collecting HLA or other haplotype data on familial disease. PMID- 7864594 TI - A note on testing the Hardy-Weinberg law across strata. AB - The problem of testing the Hardy-Weinberg law when the data are stratified in K strata is considered. Previous methods lose power when the departure from the law is irregular from stratum to stratum. Two methods based on the squared distance are proposed to overcome this problem. Simulations show that the new methods can have a dramatic improvement over the previous methods. The methods are applied to red cell glyoxalase genotype data from populations in India. PMID- 7864595 TI - We cannot manage the cost until we can manage the system. PMID- 7864596 TI - The meaning of spirituality to perioperative nurses and their patients. PMID- 7864597 TI - Preadmission brochures. PMID- 7864598 TI - Surgical hand scrub preparations. PMID- 7864599 TI - AORN priorities for perioperative nursing research. AB - The priorities for perioperative nursing research identified by the experts who participated in this Delphi study give direction to future research that can enhance a research-based nursing practice. Patient outcomes, future roles, clinical issues, staffing, and health care delivery topics frame the intricate picture of perioperative nursing research priorities. The results of this Delphi study are consistent with priorities identified in the 1988 "AORN policy, plan, and priority statement on nursing research." Perioperative nurse experts desire a professional practice that is based on scientific knowledge. Future research should generate scientific knowledge for recommended practices and activities that lead to desired patient outcomes by forging a proactive future for perioperative nursing. PMID- 7864600 TI - Metacarpophalangeal joint implant arthroplasty. AB - Rheumatoid arthritis (RA) usually requires lifelong treatment and sometimes surgery. Metacarpophalangeal joint (MCPJ) implant arthroplasty is one surgical treatment for patients with severe RA malformation of the finger joints. Although not a cure, MCPJ implant arthroplasty can enhance patients' quality of life by improving their performance of independent activities of daily living. The silicone implant acts as a spacer until tendons and connective tissues are able to control the joint's functions. Comprehensive preoperative and postoperative patient teaching and aggressive physical therapy are needed to achieve optimal outcomes in patients who undergo this surgical procedure. PMID- 7864601 TI - Perioperative considerations of vascular access for dialysis. AB - Perioperative nurses can be advocates for dialysis patients by being knowledgeable about various access routes, advantages and disadvantages of each, and associated nursing care. The longevity of vascular access devices depends on avoiding infection and blood clot formation. Perioperative nurses need to assess the knowledge level of the dialysis patient before surgical intervention in any situation. PMID- 7864602 TI - Outpatient surgery center accreditation. AB - The increase in outpatient surgery has spurred an interest in accreditation for ambulatory surgery centers. Several agencies accredit health care facilities, including the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO). This article details one ambulatory surgery center's step-by-step actions toward obtaining JCAHO accreditation. PMID- 7864603 TI - Nurses' responses to organ procurement from nonheartbeating cadaver donors. AB - Brain-dead donors (ie, heartbeating cadaver donors) have been an accepted source of transplantable organs for many years. Clinicians in some medical centers are considering nonheartbeating cadaver donors (ie, patients who decide to discontinue life-support measures and become organ donors) as another source of transplantable organs. This study explored registered nurses' responses to caring for nonheartbeating cadaver donors and described their intentions to care for such donors, their reactions to caring for them, and the meaning of these reactions and intentions. The nurses interviewed expressed resentment at the intrusion of technology; they preferred brain-dead status in organ donors; they feared legal repercussions from families; they speculated about nonheartbeating cadaver donors' ability to feel pain, and they expressed concern about withdrawing life-support measures, honoring patients' wishes, allocating nursing care as a scare resource, and witnessing family members' pain. PMID- 7864604 TI - Postoperative complications related to coronary artery bypass grafting. PMID- 7864605 TI - Attention shifts to state health care reform efforts. PMID- 7864606 TI - The Patient Protection Act will have implications for nonphysician providers. PMID- 7864607 TI - Does oral experience terminate ingestion? AB - Using data from studies of ingestive behavior in developing rat pups we demonstrate how oral experience can contribute to the termination of ingestion. In rat pups, repeated oral stimulation with sweet solutions causes a decline in oral responsiveness. The diminished responsiveness is specific to the flavor of the stimulus experienced orally and can persist for several hours. We suggest that this experience-based decrement in responsiveness is best considered "oral habituation" and that oral habituation largely accounts for the onset of satiety. Post-ingestive feedback signals may have their influence through the oral habituation process or act in the context of oral habituation. Oral habituation is also shown to depend on the pattern of stimulus presentation, a phenomenon that adds considerable complexity to assessing the contributions of oral experience to satiety. The concept of oral habituation may be useful in understanding the immediate control of ingestion and the moment-to-moment expression of ingestive behavior in adult animals. PMID- 7864608 TI - Effects of liquid preloads with different fructose/fibre concentrations on subsequent food intake and ratings of hunger in women. AB - Preloads (250 ml) of 2% or 10% fructose containing 1% soluble fibre and 1% insoluble fibre or 10% fructose with 3% soluble fibre and 1% insoluble were administered 60 min before lunch to 24 healthy women, who were slightly overweight and considerably weight concerned. The fibre consisted of guar gum, partly hydrolysed for the soluble form. The placebo consisted of a solution of sweeteners (cyclamate and saccharin). After the experiment with three preload types and a placebo, a random subset of 15 subjects returned for an experiment with one preload-type and a placebo, given 30 or 60 min before lunch. Food intake during the subsequent lunch was only significantly different from after the placebo in this subset of 15 subjects after the 10% fructose/3% soluble and 1% insoluble fibre preload after intervals of 30 or 60 min. However, energy intake of preload and meal was significantly higher than energy intake of placebo and meal. At the 30-min delay, eating rate was significantly lower after the preload than after the placebo; also, hunger ratings were lower after intake of a preload and meal than after intake of the placebo+meal, from immediately after lunch until 5 hours later. Energy intake over 24 h was not affected by administration of fructose/fibre or placebo 30 or 60 minutes before lunch in the 24 women. PMID- 7864609 TI - Development of measures of food neophobia in children. AB - In order to construct a behavioral neophobia measure for children, we had 5-, 8- and 11-year-olds choose from ten novel and ten familiar foods which ones they were willing to taste. Meanwhile, their parents indicated their own willingness to taste each of the foods, predicted the children's willingness, estimated the number of times they and their children had eaten the foods, and completed trait measures of food neophobia for themselves and the children. The children's levels of behavioral neophobia were significantly related to both their levels of trait neophobia and their parents' predictions of their willingness to eat the foods (r = 0.38 and 0.34, respectively; p < 0.001). In addition, children's and parents' behavioral and trait neophobia scores were significantly related (both r = 0.31; p < 0.001). Finally, parents but not children were more neophobic with respect to foods of animal (vs. vegetable) origin. PMID- 7864610 TI - Human responses to five concentrations of sucrose in a dairy product: immediate and delayed palatability effects. AB - Preferences for five sucrose concentrations (0, 5, 10, 20 and 40 g of sugar per 100 g of plain yogurt) were assessed in men and women by brief-exposure sensory evaluation tests and intake tests. Ten ad-libitum yogurt intake tests (with each concentration presented twice) and two sensory evaluation tests (one before and one after the series of intake tests) were conducted. Food intake in the 24 h after each test was estimated using dietary records. Sweetness intensity ratings did not change as a function of test condition. In contrast, hedonic ratings in sensory evaluation tests were more closely correlated to actual intake in experienced than in naive subjects. In intake tests the preferred sucrose concentrations were 5 and 10%. Food intake in the first few hours after yogurt intake was significantly greater on 10%-sucrose days relative to the other concentration days in men only. Although there was a tendency to eat more over the 24 h after consumption of the preferred yogurts, this effect was not statistically significant. Total daily intake, including the calories in the yogurts, was greater on intake days than on sensory evaluation days, indicating that the energy derived from the yogurts was not compensated for by a decrease in subsequent intake. PMID- 7864611 TI - Methodology, correlational analysis, and interpretation of diet diary records of the food and fluid intake of free-living humans. AB - The diet diary technique can produce reliable and valid records of the food and fluid intake of free-living humans. Procedures to maximize accuracy by motivating subjects, verifying records and minimizing bias are described. Underestimation and random error may tend to obscure relationships but does not artifactually produce them. Meal pattern analysis of the diary records relates the meal size, composition and intermeal interval to preceding conditions with univariate and multivariate regression techniques. Although causation cannot be conclusively demonstrated, the analyses can test for potential causal influences. It is concluded that the diet diary technique is the method of choice for investigations of the ingestive behaviours of free-living humans. PMID- 7864612 TI - Food cravings and taste aversions in the elderly. PMID- 7864613 TI - Are food and self-administered drugs interchangeable in baboons? PMID- 7864614 TI - Accounting for gender, age and socioeconomic differences in food choice. PMID- 7864615 TI - Exercise-induced weight loss in the rat and anorexia nervosa. PMID- 7864616 TI - Integration of sensory, somatic and social determinants of appetite for food and drink. PMID- 7864617 TI - Aging and the pursuit of slimness: dieting and body satisfaction through life. PMID- 7864618 TI - Multiple metabolic controls of feeding. PMID- 7864619 TI - Effect of meal macronutrient and energy content on human performance. AB - The effects of planned meals, varying in carbohydrate (CHO), fat and caloric content, on psychomotor performance by male subjects with unrestricted access to commercially-available foods was investigated in two residential studies. In the first study, two groups of three subjects (n = 6) completed psychomotor tasks before and after consuming a lunch consisting of 431 or 844 kcal, with caloric differences produced through covert changes in either fat or CHO content. The effects of each of four lunch conditions (low-fat, high-fat, low-CHO, high-CHO) were determined for three consecutive days. In the second study, two groups of three subjects (n = 6) received breakfast, lunch and an afternoon snack and completed psychomotor tasks after breakfast and lunch. Cumulative caloric content of the three eating occasions was approximately 700, 1200 or 1700 kcal (low, medium or high), again with differences resulting from covert changes primarily in either fat or CHO content. The effects of each of six food conditions were determined for two consecutive days. While changes in some aspects of performance were altered after meals, the effects were not related to the CHO, fat or caloric content of the meal. When subjects have unrestricted access to commercially available foods, neither calories nor the relative fat or CHO content of normal meals influence human psychomotor task performance. PMID- 7864620 TI - Identification of a 42-kDa plant mitochondrial outer membrane protein, MOM42, involved in the import of precursor proteins into plant mitochondria. AB - A 42-kDa plant outer mitochondrial membrane protein, MOM42, has been identified as an essential component of the plant mitochondrial precursor protein translocation apparatus. Immunological cross-reactivity has been detected between antibodies raised against both Neurospora and yeast mitochondrial outer membrane proteins and plant mitochondrial outer membrane proteins. Immunocompetition studies showed that import of precursors to Rieske FeS protein, ATPase su9-DHFR, and the adenine nucleotide transporter was inhibited in the presence of antibody to MOM42. The inhibition of Rieske Fes and su9-DHFR import was greater than that of the adenine nucleotide transporter. The competition studies suggest that the MOM42 is involved in the translocation of bound precursor proteins. The import data and the Western blots suggest that components of the mitochondrial import system are highly conserved. PMID- 7864621 TI - Efficacy of all-trans-beta-carotene, canthaxanthin, and all-trans-, 9-cis-, and 4 oxoretinoic acids in inducing differentiation of an F9 embryonal carcinoma RAR beta-lacZ reporter cell line. AB - A reporter cell line was established from F9 mouse teratocarcinoma cells containing the RAR beta 2 promoter coupled to the lacZ (beta-galactosidase) reporter gene. All-trans-, 9-cis-, and all-trans-4-oxoretinoic acid were equipotent in inducing cell differentiation at 1 microM, determined by induction of collagen IV mRNA expression, of morphological changes, as well as of beta galactosidase enzyme activity. By the same criteria, beta-carotene at 10 microM also induced differentiation, but less strongly and more slowly than the retinoic acids. In contrast, the oxocarotenoid (or xanthophyll) canthaxanthin, at 10 microM, had little effect on differentiation, unless preincubated in culture medium, from which 4-oxoretinoic acid was recovered and identified as a decomposition product. This indicates that canthaxanthin can act as an effective inducer of differentiation only after breakdown to active metabolites. Likewise, beta-carotene probably also acts subsequent to breakdown to retinoic acid. Throughout these experiments the response of the RAR beta promoter-lacZ reporter gene correlated well with other parameters of differentiation, making this cell line a useful system for examination of inducers of embryonal carcinoma cell differentiation. PMID- 7864622 TI - Dephosphorylation of protein kinase C substrates, neurogranin, neuromodulin, and MARCKS, by calcineurin and protein phosphatases 1 and 2A. AB - Neurogranin, neuromodulin, and MARCKS are among the most prominent substrates of protein kinase C (PKC) in the mammalian brain. These phosphoproteins were dephosphorylated by three isoforms of rat brain calcineurin, also known as calmodulin (CaM)-dependent protein phosphatase (CaMPP). The three CaMPP isozymes dephosphorylate neurogranin, the most favorable substrate among the three tested, with subtle differences in their responses to divalent metal ions, Mn2+ and Ni2+. Dephosphorylation of neurogranin by all three CaMPP isozymes, CaMPP-1, -2, and 3, were stimulated to a higher extent by Mn2+ than by Ni2+ in the presence of CaM and Ca2+. The Km values of neurogranin in the presence of Mn2+ were lower than those in the presence of Ni2+ for CaMPP-1 and -2, but that for CaMPP-3 was comparable with either divalent metal ion. The Vmax values were higher in the presence of Mn2+ than those of Ni2+ for all three isozymes. Neurogranin and neuromodulin, both phosphorylated by PKC at a single site, were dephosphorylated completely by CaMPP; however, MARCKS, phosphorylated by PKC at three sites, was partially dephosphorylated by this phosphatase. A higher extent of dephosphorylation of MARCKS could be achieved by the combination of CaMPP and protein phosphatase 2A and a complete dephosphorylation of this protein was observed with protein phosphatase 1. Protein phosphatase 1 and 2A were also effective in a complete dephosphorylation of neurogranin and neuromodulin. Amino acid sequence analysis of the tryptic phosphopeptides derived from MARCKS dephosphorylated by CaMPP and protein phosphatase 2A revealed that the former preferentially dephosphorylated Ser155 and the latter Ser162 of rat brain MARCKS. Both phosphatases dephosphorylated poorly of Ser151. Because of the high concentration of CaMPP in the brain and the colocalization of this phosphatase with major PKC substrates in the various brain regions, it is likely that CaMPP is a phosphatase with potential to reverse the action of PKC. PMID- 7864623 TI - Doxorubicin reduces the iron(III) complexes of the hydrolysis products of the antioxidant cardioprotective agent dexrazoxane (ICRF-187) and produces hydroxyl radicals. AB - Dexrazoxane (ICRF-187) is very effective in protecting against doxorubicin induced cardiotoxicity. Dexrazoxane likely acts though its metal ion binding hydrolysis product ADR-925 by reducing doxorubicin-promoted iron-based oxygen free radical damage. In this study we show that doxorubicin and epirubicin (but not daunorubicin, idarubicin, or mitoxantrone) are able to reduce iron(III)-ADR 925 and under aerobic conditions are able to produce hydroxyl radicals that are detectable by EPR spin trapping. The ability of iron(III)-ADR-925 to produce hydroxyl radicals in the presence of anthraquinones is compared with that of other ferric chelates, including those of the one-ring open hydrolysis intermediates of dexrazoxane, the tetraacid derivative of ADR-925, EDTA, DTPA, and deferoxamine. The anthraquinones that lacked an alpha-ketol side chain (daunorubicin, idarubicin, and mitoxantrone) produced much less hydroxyl radical than those that did (doxorubicin and epirubicin). The model alpha-ketol, dihydroxyacetone, was also able to promote the formation of hydroxyl radicals in the presence of iron(III) chelates. Since dexrazoxane and doxorubicin are administered together, the possibility must be considered that anthracyclines with alpha-ketol side chains may be oxidized by iron(III)-ADR-925, thus changing their antitumor activity. PMID- 7864624 TI - Purification and general properties of an oligopeptidase from Treponema denticola ATCC 35405--a human oral spirochete. AB - An endo-acting oligopeptidase (OPase) was purified to homogeneity from the cells of Treponema denticola ATCC 35405--a human oral spirochete--by a procedure that comprised a mild Triton X-100 extraction (which disintegrates the outer membrane but leaves the cells morphologically intact) and four successive fast protein liquid chromatographic steps of the extract. The activity of this oligopeptidase (formerly named "trypsin-like" enzyme and "BANA-peptidase") together with the proteinase activities of T. denticola and Porphyromonas gingivalis is utilized in a diagnostic test for human periodontal infections, but the enzyme's chemical nature has not been studied. The enzyme is a cell-associated 78-kDa protein with an isoelectric point of 6.1, and its estimated minimum peptide length was 688 amino acid residues. The OPase does not hydrolyze proteins, but hydrolyzes -X-Arg p-nitroaniline peptides between arginine and the chromogen, the optimum pH of hydrolysis covering a broad pH range (7 to 9). The OPase is not a metalloenzyme, although 1.0 mmol/liter Ca(II) increases the rate of the hydrolysis of all substrates. Ca(II) did not affect the values of the Michaelis constant. The OPase activity is not dependent on reactive SH-groups, but is suggested to depend on the catalytic triad COOH. . .His. . .Ser. The N-terminal sequence for the first 29 amino acid residues is MKQSDFEKPPIAEIKETRFEKFGKTRIDN. The purified enzyme is very sensitive to chlorhexidine acetate (mixed inhibition; Ki = 0.85 microM) and somewhat less sensitive to bacitracin (Ki(app) = 27.5 microM). The present OPase is considered to belong to the serine peptidases, functionally resembling trypsin except that the OPase does not hydrolyze proteins. The OPase may be regarded as an oligopeptidase, the substrate specificity profile of which resembles to a certain extent that of some members of the coagulation cascade. PMID- 7864625 TI - Characterization of an inducible P450 hydroxylase involved in the rice diterpene phytoalexin biosynthetic pathway. AB - Ent-isopimara-8(14),15-dien-3 beta-ol (1) was isolated from uv-irradiated rice (Oryza sativa L.) leaves. Since 1 was converted to the rice diterpene phytoalexins and oryzalexins D (ent-isopimara-8(14),15-diene-3 beta,7 alpha-diol) and E (ent-isopimara-8(14),15-diene-3 beta,9 alpha-diol) in uv-irradiated rice leaf microsome fraction in the presence of oxygen and NADPH, it was concluded that 1 was the biosynthetic precursor of these oryzalexins. This enzyme reaction was inhibited by cytochrome P450 inhibitors such as piperonyl butoxide, SKF-525A, paclobutorazole, metyrapone, cytochrome c, and carbon monoxide. The lack of inhibitory activity of 1 for spore germination of Pyricularia oryzae indicates that the final cytochrome P450-dependent hydroxylation steps in converting 1 to oryzalexins D and E are essential for the production of rice phytoalexins with antifungal activities. PMID- 7864626 TI - Expression, purification, and characterization of the human squalene synthase: use of yeast and baculoviral systems. AB - We have cloned and utilized a cDNA corresponding to the human squalene synthase gene to generate active enzyme from yeast and baculoviral expression systems. Expression of human squalene synthase in yeast resulted in production of active enzyme in cellular lysates. The presence of the active human enzyme, however, was insufficient to rescue growth of spores defective in yeast squalene synthase function, suggesting that structural differences in the yeast and human enzymes may affect localization or folding of the protein. Expression of the human enzyme in Sf-9 insect cells after infection with recombinant baculovirus encoding the human squalene synthase gene resulted in detection of substantial enzymatic activity in cell lysate preparations. Following extraction from the Sf-9 cells, the human enzyme was purified to near homogeneity utilizing a series of ion exchange chromatography steps with an overall yield of purified protein of approximately 5 mg per liter of Sf-9 cell culture. The purified enzyme was characterized through steady-state kinetic and physical measurements and the kinetic constants are consistent with values observed for other squalene synthases. Zaragozic acid C was found to be a competitive inhibitor with respect to farnesyl pyrophosphate and has a Kis value of 250 pM (@ [NADPH] = 5 mM). Inhibition experiments with zaragozic acid C at low (approximately 0.5 x Km) and high (approximately 10 x Km) concentrations of NADPH indicated that the inhibitor does not bind in the enzyme's NADPH binding domain. These studies demonstrate that the human enzyme can be prepared from baculovirus-infected Sf-9 cells in a catalytically active configuration and in sufficient quantities to allow for further biochemical, kinetic, and structural characterization. PMID- 7864627 TI - Biosynthesis of proteoglycans and hyaluronic acid by rat oral epithelial cells (keratinocytes) in vitro. AB - Biosynthesis of complex carbohydrates, including sulfated glycoproteins, hyaluronic acid (HA), and proteoglycans (PGs), synthesized by rat oral epithelial cells (keratinocytes) in culture were studied by metabolic labeling protocols using [35S]sulfate and [3H]glucosamine in combination with differential enzymatic digestion and analytical gel filtration. The epithelial cells synthesized a major sulfated glycoprotein species with an apparent molecular size approximately 50 kDa, which accounted for approximately 46% of the total 35S incorporation. HA was a relatively minor component of 3H-labeled macromolecules (approximately 4% of the total 3H incorporation), and almost all of it was secreted into the medium. PGs accounted for approximately half of the 35S incorporation, of which about 30% was secreted into the medium and the remainder associated with the cell layer. The majority of PGs (75% of the secreted and 97% of the cell-associated) contained heparan sulfate (HS) and had an apparent molecular weight of approximately 150,000. Cell-associated HSPGs had a core protein of approximately 70 kDa with HS chains of approximately 64 kDa, while HSPG in the medium had a core protein of approximately 50 kDa with HS chains of the same average size as those of the cell-associated HSPG. Of the total cell-associated HSPGs, glycosylphosphatidyl inositol-anchored forms, plasma membrane intercalated forms and those associated with basolateral pericellular matrix accounted for approximately 3%, 56% and approximately 4% of the total, respectively. Approximately one third of the cell-associated HSPGs were intracellular components most likely generated through intracellular degradation processes following endocytosis. Cell surface HSPGs synthesized by keratinocytes may be involved in some biological roles such as the regulation of normal epithelial turnover and defense mechanisms involving interactions with various oral pathogens. PMID- 7864628 TI - Veratryl alcohol-mediated indirect oxidation of phenol by lignin peroxidase. AB - Veratryl alcohol (VA) oxidation by lignin peroxidase (LiP) was inhibited by phenol. The enzyme was quickly converted to compound III, an inactive intermediate. However, as soon as VA began to be oxidized, compound II was observed. The lag period before VA oxidation was affected by the concentrations of both phenol and VA. The addition of VA increased the extent of phenol oxidation and the kinetics of phenol oxidation in the presence of VA were similar to those of VA oxidation. Previously it was shown that the VA cation radical (VA.+) was responsible for the conversion of compound III back to ferric enzyme [D. P. Barr and S. D. Aust (1994) Arch. Biochem. Biophys. 312, 511-515]. Here we observed that the reversion of compound III to active ferric enzyme in the presence of VA was prevented by addition of phenol, suggesting that VA.+ oxidizes phenol to phenoxyl radical. This hypothesis was also supported by the observation that O2 consumption during VA oxidation was inhibited by the addition of phenol. All of these results suggested that VA was first oxidized by LiP to VA.+ and then it oxidized phenol to phenoxyl radical while VA.+ was reduced back to VA. Activity was lost as compound III accumulated since the VA.+ was consumed by the oxidation of phenol. After all of the phenol was oxidized, VA.+ became available to convert compound III back to ferric enzyme. PMID- 7864629 TI - Analysis of substrate recognition determinants in a synthetic peptide containing the Tyr 1173 autophosphorylation site of the epidermal growth factor receptor. AB - The epidermal growth factor receptor contains five autophosphorylation sites in its C-terminal region. Synthetic peptides based on the major autophosphorylation site at Tyr 1173 were tested as substrates of the intracellular domain of the epidermal growth factor receptor. A peptide containing acidic residues N-terminal to the substrate Tyr as well as the Tyr-Met-Xaa-Met motif of the insulin receptor substrate 1 had a Km value of 15 microM, the lowest value for a synthetic peptide reported to date. Another important residue contributing to substrate binding is the Tyr itself, or more specifically, the hydroxyl group of the Tyr. Substituting Phe for Tyr results in a peptide that is ineffective as an inhibitor of kinase phosphorylation. However, substitution of a Ser residue does not restore a functional substrate, indicating specificity for the Tyr hydroxyl. Secondary structure algorithms predicted that the peptide substrate based on the native sequence at Tyr 1173 would have a propensity to adopt a helical conformation in solution. Circular dichroism spectroscopy confirmed this prediction. The secondary structure of the peptide substrate is significant in its consistency with the idea that secondary structure is an important determinant in substrate recognition by protein tyrosine kinases. PMID- 7864630 TI - Prostaglandin H synthase-1: evaluation of C-terminus function. AB - The first committed step in prostaglandin biosynthesis is catalyzed by prostaglandin H synthase, an enzyme localized to the endoplasmic reticulum (ER) membrane in a variety of cells. Several types of C-terminal region peptide sequence motifs have been found to lead to ER retention of other proteins. We have tested the potential role for such signals in the ER localization and catalytic activity of human isoform-1 of the synthase (PGHS-1). PGHS-1 mutants with alterations in the C-terminus designed to disrupt potential retention signals were expressed in transfected COS-1 cells. The mutations included: substitution of valine for the ultimate leucine residue (position 600) to disrupt a KDEL-type signal, substitution of a neutral glutamine for arginine at position 595 to disrupt signals based on positive charge, and deletion of the last six residues, to remove all of the wild-type extreme C-terminus. The subcellular localization of each recombinant PGHS-1 was assessed by differential centrifugation and by immunofluorescence microscopy. None of the mutations led to a significant change in the distribution of PGHS-1 between microsomes and other cellular fractions. Immunostaining of wild-type PGHS-1 and all of the mutants colocalized with that of protein disulfide isomerase, an ER marker protein. However, mutation of the terminal leucine or deletion of the last six residues did lead to loss of cyclooxygenase activity. Mutation of the terminal leucine also altered the pattern of fragments produced by limited proteolysis, indicating that this mutation led to changes in the polypeptide folding which might account for the loss of activity. The results indicate that the extreme C-terminal region is important to the functional integrity of PGHS-1, but it is not an essential part of the intracellular targeting mechanism. PMID- 7864631 TI - Inorganic phosphate promotes redox cycling of iron in liver microsomes: effects on free radical reactions. AB - The phosphate buffer concentration used in spin trapping experiments with liver microsomes markedly influenced rates of free radical formation from ethanol and dimethylsulfoxide, but not from carbon tetrachloride. Effects of phosphate concentration on ethanol radical formation were abolished by addition of deferoxamine or bathophenanthrolene, indicating that an iron-phosphate complex might be involved. High concentrations of phosphate stimulated rates of microsomal Fe+3 reduction and facilitated the mobilization of microsomal nonheme iron, but had little effect on a variety of microsomal monooxygenase enzyme activities. Although microsomal oxygen utilization and superoxide production were relatively unaffected by phosphate, hydrogen peroxide concentrations were markedly decreased in the presence of high concentrations of phosphate. Taken together, the data suggest that a ferric-phosphate complex may be enzymatically reduced by microsomal enzymes and NADPH. Reoxidation of ferrous ion is nonenzymatically promoted by phosphate and/or H2O2 produced by the microsomes. During the process of reoxidation, one or more oxidizing intermediates may be formed which initiate secondary free radical reactions. Although the reactivity of the intermediate(s) is similar to that of the hydroxyl radical, no spin trapping evidence was obtained to support this assignment. PMID- 7864632 TI - Utilization of copper as a paramagnetic probe for the binuclear metal center of phosphotriesterase. AB - Bacterial phosphotriesterase catalyzes the hydrolysis of organophosphate triesters. To be active, the enzyme requires that two divalent cations are bound. These metal ions are bound in close proximity to one another as a binuclear center. To characterize the structure and function of the binuclear metal binding sites, we have prepared the copper-substituted enzyme. The kinetic data indicate that this enzyme is essentially inactive toward the hydrolysis of phosphotriesters. The EPR signal arising from the copper-substituted enzyme is nearly axial, with g parallel = 2.24 and g perpendicular = 2.05 and shows at least seven superhyperfine transitions in the g perpendicular region with A perpendicular = 1.45 x 10(-3) cm-1. These splittings are consistent with the direct ligation of more than one nitrogen to the metal center. The average spin quantitation of copper-substituted enzymes are 0.6 spin/Cu, approximately half of that observed for noninteracting Cu2+ ions. The spin intensity increases to ca. 1 spin/Cu when samples are denatured with acid. The binding of metal ions to the designated alpha and beta sites is highly synergistic (i.e., the metal ions bind in pairs). Mixed metal complexes of the type Cu/X and X/Cu were prepared. When X is a diamagnetic ion (Zn2+ or Cd2+), the spin quantitation increases, but when X is the paramagnetic Co2+ ion, the spin quantitation decreases. This behavior indicates that the low spin intensities observed for copper-substituted phosphotriesterase arise from spin-coupling of the two adjacent Cu2+ ions. The addition of dithiothreitol, ascorbate, or dithionite to the copper-substituted phosphotriesterase results in nearly the complete loss of spin intensity. This indicates that the bound coppers can be reduced to the cuprous state. PMID- 7864633 TI - Mannosylphosphoryldolichol-mediated O-mannosylation of yeast glycoproteins: stereospecificity and recognition of the alpha-isoprene unit by a purified mannosyltransferase. AB - Mannosylphosphoryldolichol (Man-P-Dol):protein O-mannosyltransferase (PMT1) was solubilized by extracting a crude microsomal fraction from Saccharomyces cerevisiae with 1.2% Chaps-0.5% desoxycholate and purified 120-fold by standard chromatographic procedures. These very stable, partially purified preparations of PMT1 catalyzed the transfer of mannosyl units from exogenous Man-P-Dol to serine/threonine residues in the synthetic peptide acceptor, Tyr-Asn-Pro-Thr-Ser Val-NH2, forming O-mannosidic linkages of the alpha-configuration. The specificity of yeast PMT1 was defined with respect to the recognition of the saturated alpha-isoprene unit, the chain length of the dolichyl moiety, and the anomeric configuration of the mannosyl-phosphoryl linkage of the lipophilic mannosyl donor. When Man-P-Dol95 and mannosylphosphorylpolyprenol (Man-P-Poly95), which contains a fully unsaturated polyprenyl chain, were compared as substrates, the initial rate for peptide mannosylation was dramatically higher with Man-P Dol95 relative to Man-P-Poly95. The chain length of the dolichyl moiety also influenced the mannolipid-enzyme interaction as the partially purified PMT1 had a higher affinity for Man-P-Dol95 than for Man-P-Dol55. When beta-Man-P-Dol95 was compared with chemically synthesized alpha-Man-P-Dol95 as a mannosyl donor, a strict stereo-specificity was observed for the presence of a beta-mannosyl phosphoryl linkage. In summary, a procedure for isolating a stable, partially purified preparation of PMT1 from S. cerevisiae is described. Enzymological studies with these preparations of PMT1 provide the first evidence that the recognition of the lipophilic mannosyl donor is stereospecific. These results also demonstrate that maximal O-mannosylation of serine/threonine residues in yeast glycoproteins catalyzed by the partially purified preparation of PMT1 requires the presence of a saturated alpha-isoprene unit in the dolichyl moiety of Man-P-Dol. PMID- 7864634 TI - Shedding of tyrosine and serine/threonine ecto-protein kinases from human leukemic cells. AB - Ecto-protein kinases (ecto-PK), primarily of the serine/threonine kinase type, have been previously described on the surface of various normal, transformed, and tumor cells. We have found that in the presence of ATP and Mg2+, exogenously added substrates such as phosvitin and poly(Glu4-Tyr) are phosphorylated by intact K562 erythroleukemia, HL60 promyelocytic leukemia, and U937 histiocytic leukemia human cells. Phosphoamino acid analysis indicated that phosvitin, histone H2B, casein, and protamine are phosphorylated on serine and threonine residues, whereas poly(Glu4-Tyr) is phosphorylated on tyrosine. We also present evidence showing that the C9 complement protein, a key component of the membranolytic protein complex of the complement system, is exclusively phosphorylated by the K562 cells on serine residues. Phosphorylation of poly(Glu4 Tyr) is markedly enhanced by Mn2+, whereas C9 phosphorylation is rather inhibited by Mn2+. It is concluded that human leukemic cells express on their surface two types of ecto-PK, one phosphorylating serines and threonines and one specific to tyrosines. The ecto-PKs are spontaneously shed from fully viable cells into the medium in a temperature-dependent manner. Upon sedimentation of cell supernatants at 100,000g, the ecto-PKs are found sedimented with small membrane vesicles. Treatment of intact K562 cells or of released membrane vesicles with bacterial phospholipase C, but not with trypsin or pronase, releases the two types of ecto PK from the cell or vesicle membrane, respectively. This is accompanied by a marked increase in the released phosphorylating activity. It is, therefore, suggested that these ecto-PKs are either covalently linked to phospholipids or strongly attached to lipid-anchored molecules in the cell surface membrane. Several endogenous proteins in the released membranes are phosphorylated by the ecto-PKs on serines and to a lesser extend on threonines. Two proteins (PTP79 and PTP54) are phosphorylated in a manganese-dependent manner on tyrosines. PMID- 7864635 TI - Four ferredoxins from Japanese radish leaves. AB - We detected three ferredoxin components, a, b, and c, in green shoots of Japanese radish seedlings by hydrophobic HPLC analysis using a phenyl-5PW column. All components were also present in mature leaves. Component a was further separated into two components, a1 and a2, by reversed-phase HPLC after carboxymethylation. The existence of four ferredoxins in the photosynthetic tissue of a single plant species is reported here for the first time. Each individual ferredoxin component was isolated, and its primary structure was analyzed for comparison with the two leaf ferredoxins, L-Fds A and B, isolated by Wada et al. (J. Biochem. 105, 619 625 (1989)). The primary structures of components a1, a2, and b were all found in 12 possible structures of L-Fd A deducible from its microheterogeneities. This led us to conclude that L-Fd A is a mixture of three ferredoxins corresponding to components a1, a2, and b. The complete primary structure of component c was established by sequencing of the whole protein and of peptides generated by protease digestion. The N-terminal structure of component c was identical with L Fd B up to the 11th amino acid residue, suggesting that this component is the same ferredoxin as L-Fd B. PMID- 7864636 TI - Purification and characterization of S-linalool synthase, an enzyme involved in the production of floral scent in Clarkia breweri. AB - S-Linalool is one of the volatiles emitted by Clarkia breweri Grey [Green] flowers to attract its moth pollinator. S-Linalool synthase, the enzyme that stereoselectively converts the ubiquitous C10 intermediate GPP to S-linalool, is abundant in stigmata of freshly opened flowers, and it was purified to > 95% homogeneity by anion-exchange and hydroxyapatite chromatography. S-Linalool synthase is operationally soluble as are other monoterpene synthases, has a Km of 0.9 microM for geranyl pyrophosphate, exhibits a strict requirement for a divalent metal cofactor with a preference for Mn2+ (Km = 45 microM), and shows an optimal pH of 7.4. The enzyme is active as a monomer of 76 +/- 3 kDa as determined by gel permeation chromatography and polyacrylamide gel electrophoresis. Neither S- nor R-linalyl pyrophosphates are substrates for the C. breweri S-linalool synthase, although this tertiary allylic pyrophosphate ester is a bound intermediate in the biosynthesis of cyclic monoterpenes from geranyl pyrophosphate in many plant species, where it also serves as an alternate substrate. PMID- 7864637 TI - Mammalian tissue trypsin-like enzymes: substrate specificity and inhibitory potency of substituted isocoumarin mechanism-based inhibitors, benzamidine derivatives, and arginine fluoroalkyl ketone transition-state inhibitors. AB - Amino acid and peptide thioesters which contained Arg or Lys in the P1 position were tested as substrates for rat skin tryptase, and the kinetic constants Kcat/KM for the better substrates such as Z-Aba-Arg-SBzl, and Z-Gly-Arg-SBzl were over 5,000,000 M-1 s-1. The inhibitory potency of arginine fluoroalkyl ketones, benzamidine derivatives, and substituted isocoumarins containing basic functional groups was studied with rat skin tryptase, human lung tryptase, human skin tryptase, and bovine trypsin. 1-Naphthoyl-Arg-CF3 was the best arginine fluoroalkyl ketone reversible inhibitor for rat skin tryptase with a KI of 0.9 microM. 1-(4-Amidino-phenyl)-3-(4-phenoxyphenyl) urea showed competitive inhibition against bovine trypsin and rat skin tryptase with KI values of 2 and 4 microM, respectively. Isocoumarin derivatives with isothioureidoalkoxy substituents at the 3 position were potent irreversible inhibitors of these three tryptases with Kobs/[I] values of 10(4)-10(5) M-1 s-1. 4-Chloro-3-(2 isothioureido)ethoxy-7-phenylcarbamoylaminoisocou marin and 7 benzylcarbamoylamino-4-chloro-3-(3-isothioureido)propox yisocoumarin inactivated trypsin and formed stable trypsin-inhibitor complexes which regained less than 8% of activity upon standing in the pH 7.5 buffer and regained 30-75% of activity in the presence of 0.3 M NH2OH after 1 day. In contrast, the complexes with rat skin tryptase regained activity rapidly, indicating differences in the inhibition mechanism and active site structures of these related enzymes. PMID- 7864638 TI - Influence of calcium on NADH and succinate oxidation by rat heart submitochondrial particles. AB - Physiological increases in matrix calcium are known to stimulate three mitochondrial dehydrogenases. In mitochondria isolated from rat heart, calcium stimulates rates of State 3 respiration during oxidation of succinate and of several NAD-linked substrates. In this study, we investigated the effects of calcium on NADH dehydrogenase and succinate dehydrogenase activities since the mechanism of these effects is unresolved. The respiratory activities of intact mitochondria and submitochondrial particles (SMP) were compared during incubation in media containing either ethylene glycol bis(beta-aminoethyl ether)-N,N' tetraacetic acid (EGTA) or a Ca2+/EGTA buffer (approximately 1 microM free Ca2+). In intact mitochondria oxidizing 20 mM glutamate plus 2 mM malate, the membrane potential (delta psi) and matrix NAD(P)H were maintained at higher levels, and the maximal rate of ADP-stimulated respiration (State 3) was increased twofold by the presence of calcium. With succinate as substrate, calcium stimulated State 3 respiration but it did not influence the pyridine nucleotides redox state or membrane potential. Stimulation of succinate-supported respiration by addition of 6-10 microM ADP in the presence of hexokinase caused a sudden decrease in NAD(P)H and collapse of delta psi. This effect was not caused by inhibition of succinate dehydrogenase or by opening of the nonspecific pore. Calcium did not influence the oxidation of succinate by SMP containing either activated or nonactivated succinate dehydrogenase. In addition, calcium did not alter the kinetics of succinate dehydrogenase activation. Calcium and magnesium, in the concentration range of 0.02 to 5 mM, did not influence the NADH dehydrogenase activity of SMP. Energization of SMP by oligomycin addition, however, dramatically influenced the kinetic properties of NADH dehydrogenase. It is proposed that in heart mitochondria, calcium does not affect directly the components of electron transport but it may influence the activity of NADH dehydrogenase indirectly by increasing delta psi. PMID- 7864639 TI - Inhibitors of pig kidney trehalase. AB - Trehazolin, a new trehalase inhibitor isolated from the culture broth of Micromonospora, was reported to be a highly specific inhibitor for porcine and silk worm trehalases with IC50 values of 5.5 x 10(-9) and 3.7 x 10(-9) M, respectively (O. Ando, H. Satake, K. Itoi, A. Sato, M. Nakajima, S. Takashi, H. Haruyama, Y. Ohkuma, T. Kinoshita, and R. Enokita (1991) J. Antibiot. 44, 1165 1168). We also found that trehazolin is a very powerful and quite specific inhibitor against purified pig kidney trehalase, giving an IC50 value of 1.9 x 10(-8) M. Lineweaver-Burk plots showed that this compound was a competitive inhibitor of the trehalase. However, even at concentrations of 200 micrograms/ml, trehazolin did not inhibit the rat intestinal maltase or sucrase, yeast alpha glucosidase or almond beta-glucosidase. Validoxylamine A and validamycin A, two other trehalase inhibitors, showed potent competitive inhibition against purified pig kidney trehalase, with IC50 values of 2.4 x 10(-9) and 2.5 x 10(-4) M, respectively. On the other hand, validoxylamine A was almost inactive against rat intestinal sucrase and maltase, with some inhibition being observed at millimolar concentration. A number of other glucosidase inhibitors, such as MDL 25637, castanospermine, and deoxynojirimycin were also tested against the purified trehalase and showed reasonable inhibitory activity. PMID- 7864640 TI - Bafilomycin A1 inhibits IL-1-stimulated proteoglycan degradation by chondrocytes without affecting stromelysin synthesis. AB - Interleukin-1 alpha (IL-1) stimulated the release of degraded proteoglycan from primary cultures of chondrocyte monolayers in a time- and dose-dependent fashion. Bafilomycin A1, a specific inhibitor of the vacuolar H(+)-ATPase, efficiently blocked acidification of the chondrocyte vacuolar system. Under these conditions IL-1-stimulated proteoglycan degradation was inhibited by bafilomycin A1 with an IC50 of < 10 nM in both chondrocyte monolayers and articular cartilage explants. This concentration was at least 100-fold less than that required to partially inhibit total protein synthesis. In chondrocyte monolayers, bafilomycin A1 could be added several hours after IL-1 and complete inhibition was still observed. Tumor necrosis factor-alpha and retinoic acid also stimulated proteoglycan degradation in chondrocyte monolayers, and in both cases the response was inhibited by bafilomycin A1. These results suggest that maintenance of vacuolar acidity is required for cytokine stimulated proteoglycan degradation and that this requirement is at a point distal to receptor binding and early signal transduction events. IL-1 also stimulated the synthesis and secretion of prostromelysin by chondrocyte monolayers, however, under conditions in which IL-1 stimulated proteoglycan release was totally blocked by bafilomycin A1, there was no effect on IL-1-stimulated stromelysin secretion or stromelysin enzyme activity. These results, in which stromelysin synthesis and proteoglycan degradation were dissociated, suggest that an additional enzyme is responsible for proteoglycan degradation in this chondrocyte monolayer system. PMID- 7864641 TI - Effects of anoxia on protein phosphatase in turtle organs: purification and properties of protein phosphatase type-1 from turtle liver. AB - Protein phosphatase type 1 (PP-1) was analyzed in organs of the red-eared slider turtle, Trachemys scripta elegans, a species capable of long-term anoxia survival. During anoxic submergence at 7 degrees C, PP-1 activity in liver rapidly decreased to 63% of the control value within the first hour and remained suppressed over the subsequent 20 h of anoxia. PP-1 activity was also suppressed in red skeletal muscle during anoxia and dropped transiently (after 1 h) in brain but did not change in heart or white muscle. PP-1 was purified from turtle liver using polyethylene glycol fractionation and chromatography on DEAE-cellulose, blue dextran, Sephacryl S-200, and ADP-agarose. A 3000-fold purification was achieved with a final specific activity of 3156 nmol released min-1 mg protein-1 using 32P-labeled phosphorylase a as the substrate. Turtle liver PP-1 was a monomer of molecular mass 37 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis or 38 +/- 2 kDa by Sephacryl S-200 gel filtration. The enzyme was inhibited by okadaic acid (Ki 12.6 +/- 1.4 nM) and AMP (Ki 23 +/- 2 microM) as well as by ADP, ATP, and IMP. Regulation of liver PP-1 appears to be an integral part of anoxia-induced changes in liver glycogenolysis and metabolic rate suppression. PMID- 7864642 TI - Laparotomy causes a transient induction of rat liver serine dehydratase mRNA. AB - Rat liver serine dehydratase mRNA shows rhythmicity with a high level at the onset of dark (19:00) and a low level at the onset of light (07:00). We have examined the effect of stress (laparotomy) on the rhythm. Upon laparotomy at 09:00 or 17:00, a marked induction of serine dehydratase mRNA occurred 2 h after operation. The elevated mRNA level then decreased and the original mRNA rhythm resumed 2 days later. By contrast, the transcription activator protein DBP mRNA level which shows a similar oscillation was not affected by this treatment. The induction was also seen in adrenalectomized rats that had been treated with hydrocortisone but not with saline or noradrenaline, indicating that glucocorticoids are absolutely necessary for the induction. Pretreatment of rats with phenoxybenzamine, and prazosin prevented the effect of laparotomy, but propranolol and yohimbine had no effect, indicating the necessity of the alpha 1 adrenergic stimulation for the induction. These results suggest that laparotomy releases glucocorticoids and neural noradrenaline that stimulates alpha 1 adrenergic receptors, thereby leading to the serine dehydratase gene expression. PMID- 7864643 TI - Inactivation of lignin peroxidase by hydrogen peroxide during the oxidation of phenols. AB - The oxidation of phenols by lignin peroxidase (LiP) was characterized by a rapid decrease in enzyme activity. The initial oxidation rate of phenol decreased at moderately high (i.e., 400 microM) concentrations of H2O2. Similar results were obtained with several phenols. However, LiP was not inactivated during the oxidation of veratryl alcohol (VA). The apparent second-order rate constants for the reaction of compound II with phenol and VA at pH 3.5 were very similar, about 2.1 x 10(4) and 4.7 x 10(4) M-1 s-1, respectively. However, unlike VA, phenols could not convert compound III back to ferric enzyme. The visible absorption spectra of compound II and III were observed during oxidation of VA and phenols, respectively. These results suggest that the inactivation of LiP during the oxidation of phenols was mainly due to the accumulation of compound III, which was attributed to the inability of phenols or phenoxyl radicals to revert compound III to ferric enzyme. All of these results also suggested that the inactivation mechanism of LiP during oxidation of phenols was different from that during oxidation of anisyl alcohol, since anisyl alcohol was neither a substrate of compound II nor could it revert compound III [K. Valli et al. (1990) Biochemistry 29, 8535-8539 and R.S. Koduri and M. Tien (1994) Biochemistry 33, 4225-4230]. PMID- 7864644 TI - Analysis and quantitation of splicing variants of the TPA-inducible PGHS-1 mRNA in rat tracheal epithelial cells. AB - Previously we reported that 12-myristate 13-acetate diester (TPA) and dexamethasone regulate the expression of a putative prostaglandin G/H synthase-1 (PGHS-1) gene in a transformed, immortalized rat tracheal epithelial cell line (EGV-6). Here we report the cloning and sequencing of the cDNA for this gene. Two transcripts of similar size but differing in their 5' ends were detected. One transcript contains the complete 5' coding and noncoding regions, while the other form has an apparently intronic sequence in place of these regions. This aberrantly spliced form lacks codons 1-36. Northern analysis and quantitative PCR indicated that more than 90% of the PGHS-1 mRNA in EGV-6 cells has the aberrantly spliced 5' end. TPA treatment increases the expression of only the complete PGHS 1 mRNA, elevating it to 50% of the total PGHS-1 transcript pool. Levels of the aberrant mRNA are not affected by TPA treatment. A comparison among EGV-6 cells, primary rat tracheal epithelial (RTE) cultures, and rat fibroblasts showed that all three cell lines have similar levels of the aberrantly spliced PGHS-1 mRNA. RTE cells and fibroblasts, unlike EGV-6 cells, also contain properly spliced PGHS 1 mRNA, at levels 100-fold higher than the level of aberrant PGHS-1 mRNA. TPA does not regulate either of the PGHS-1 transcripts in RTE or rat fibroblast cells. These results confirm the induction of functional PGHS-1 mRNA by TPA only in EGV-6 cells. PMID- 7864645 TI - Hemoglobin-induced lipid peroxidation in the retina: a possible mechanism for macular degeneration. AB - To investigate a possible link between subretinal hemorrhage and macular degeneration, oxyhemoglobin (HbO2) or methemoglobin (metHb) was incubated with retinal homogenate and unsaturated phospholipid peroxidation was monitored by (a) assay of thiobarbituric acid-reactive substances (TBARS), (b) luminescence originating from an energy transfer of lipid-degraded products to rose bengal, and (c) the decrease in composition of highly unsaturated fatty acids of phospholipids. TBARS formation and rose bengal luminescence in the case of metHb induced lipid peroxidation were about 1.5 times greater than those in HbO2 induced lipid peroxidation. alpha-Tocopherol, a lipid-soluble antioxidant, and docosahexaenoic acid, a major unsaturated fatty acid, were slightly more rapidly decomposed after a 60-min incubation with metHb than with HbO2 at the same concentration. Atomic absorption analysis revealed that an equal concentration of iron was released from both HbO2 and metHb during incubation with retinal homogenates. The released iron may promote microsomal phospholipid peroxidation in the presence of endogenous ascorbate or NADPH-dependent cytochrome P-450 reductase because ascorbate oxidase and p-chloromercuribenzoic acid (an inhibitor of sulfhydryl enzymes) inhibited metHb- or HbO2-induced lipid peroxidation. MetHb induced lipid peroxidation in retina was inhibited by KCN or NaN3, which binds to FeIII of metHb. KCN or NaN3 had no effect on HbO2-induced lipid peroxidation, because conversion of HbO2 to metHb, which can proceed in HbO2 incubated with phospholipid liposome, did not occur in retinal homogenates. It is concluded that metHb induces peroxidation of retinal unsaturated phospholipids (1) directly and (2) by releasing iron. PMID- 7864646 TI - Structural and functional properties of the 34-kDa fragment produced by the N terminal chymotryptic cleavage of glutathione transferase P1-1. AB - Limited proteolysis of glutathione transferase P1-1 (GSTP1-1) by chymotrypsin generates a 34-kDa GSTP1-1 fragment (a dimer of the 17-kDa subunit composed by residues 48-207) containing the whole C-terminal domain and a part (about 15%) of the N-terminal domain (residues 48-76, i.e., the structural elements beta 3, beta 4, and alpha C). The structural and functional properties of this large fragment have been investigated by analyzing its binding properties to 2-p toluidinylnaphthalene-6-sulfonate (TNS) extrinsic probe, the TNS displacement technique, and the molecular modeling approach. The results obtained indicated that the 34-kDa GSTP1-1 fragment maintains an hydrophobic pocket with the same structural properties of the corresponding GSTP1-1 hydrophobic binding site. In addition, the 34-kDa GSTP1-1 binds a number of hydrophobic compounds such as 1 chloro-2,4-dinitrobenzene, hemin, and bilirubin with the same affinity of the native enzyme. Being structurally and functionally autonomous, this fragment, mostly constituted by domain II, appears as an independent folding unit in the protein. Nevertheless, in the entire native protein, interdomain interactions occur and are responsible for the major solvent exposure of the H-site in the presence of glutathione. PMID- 7864647 TI - Insulin enhances glucocorticoid receptor-mediated induction of gene expression independent of a specific insulin response element. AB - We have established a system in which we observe a synergistic interaction between insulin and glucocorticoids. This includes chimeric genes constructed to contain synthetic glucocorticoid-responsive elements, 5' of the HSV thymidine kinase promoter and the chloramphenicol acetyltransferase reporter gene. The magnitude of induction of gene expression by glucocorticoid was dependent on the number of GREs. Insulin alone had virtually no effect on the expression of any of these genes but together with dexamethasone acted in a synergistic manner. This synergy diminished as the number of GREs in the promoter increased. The synergy is independent of promoter sequences other than the GREs and a functional TATAA box. Three different approaches demonstrate that the effect of insulin is not directly on the glucocorticoid signal transduction pathway. Insulin does not change the dose-response relationship for dexamethasone. The effect of insulin is independent of the intracellular concentration of glucocorticoid receptor. The effect is independent of any specific domain of the glucocorticoid receptor. The target of insulin action is likely to be part of the normal host cell transcriptional initiation complex or a putative adaptor molecule. PMID- 7864648 TI - Infrared analysis of ligand- and oxidation-induced conformational changes in hemoglobins and myoglobins. AB - Effects of the binding of O2 and CO to heme iron (II) of deoxy forms and of the oxidation of deoxy forms to aquoiron (III) complexes on the infrared spectra of hemoglobins and myoglobins have been examined. Spectra were measured for aqueous solutions 3-4 mM in heme of human, bovine, and equine hemoglobins and sperm whale, bovine, and equine myoglobins in 10 mM sodium phosphate buffer, pH 7.4, at 20 degrees C. All ligand binding and oxidation reactions resulted in similar spectral shifts in the region 1665 to 1670 cm-1, a portion of the amide I region assignable to beta-turn structure. There were no other significant changes in the amide I region, a finding consistent with no other alterations in secondary structure. The major bands near 1655 cm-1 associated with alpha-helices were consistently at 2 cm-1 lower wavenumber for myoglobins than for hemoglobins. The changes in solution infrared spectra observed in this study may result at least in part from conformational changes at the FG corner associated with movements of F and E helices that have been noted previously in crystal structures. PMID- 7864649 TI - Rat testicular carboxylesterase: cloning, cellular localization, and relationship to liver hydrolase A. AB - We recently purified from rat liver microsomes a carboxylesterase, designated hydrolase A, that catalyzes the hydrolysis of para-nitrophenylacetate with high affinity (Km approximately 25 microM) and is very sensitive to the inhibitory effects of phenylmethylsulfonyl fluoride (PMSF). Based on its catalytic properties, isoelectric point, and N-terminal amino acid sequence, hydrolase A corresponds to the pI 6.1 esterase cloned from a rat liver cDNA library by Robbi et al. (Biochem. J. 269, 451-458, 1990). A PMSF-sensitive esterase with high affinity toward para-nitrophenylacetate is also present in testicular microsomes at levels that slightly exceed those in liver microsomes. Antibody against purified hydrolase A recognizes a 57-kDa protein in both liver and testicular microsomes, suggesting that hydrolase A is expressed to a high degree in both tissues. To determine whether the testicular carboxylesterase is identical to hydrolase A, a rat testicular cDNA library was constructed and screened with antibody against hydrolase A. A 709-bp cDNA was isolated from immunopositive clones. Screening the same cDNA library by polymerase chain reaction (PCR) with one primer based on the sequence of the 709-bp cDNA and one primer based on the sequence of the adjoining lambda gt11 arm yielded a 1.1-kb cDNA that overlapped with the 709 bp-sequence. Together these two cDNA fragments spanned a 1792-bp sequence with an opening reading frame encoding 518 amino acids, which corresponds to approximately 95% of the C-terminal sequence of the liver pI 6.1 esterase (i.e., hydrolase A). Except for four nucleotide differences at positions 479, 855, 1335, and 1350, the sequence of the testicular cDNA was identical to the cDNA sequence of the liver pI 6.1 esterase reported by Robbi et al. None these changes results in an amino acid substitution. However, these four base substitutions were not observed when a cDNA encoding hydrolase A was isolated from a rat liver cDNA library by PCR. These results establish that the same carboxylesterase, namely, hydrolase A, is expressed in rat liver and testis. The levels of mRNA for hydrolase A in various rat tissues was estimated from Northern blots probed with the 709-bp cDNA isolated from the rat testicular cDNA library. A approximately 2-kb mRNA for hydrolase A was detected in liver, testis, lung, and prostate, which confirms the tissue distribution of hydrolase A based on catalytic activity and Western immunoblotting.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7864650 TI - Hydroxyl radical generation during mitochondrial electron transfer and the formation of 8-hydroxydesoxyguanosine in mitochondrial DNA. AB - Production of hydroxyl radicals (HO.) by substrate-supplemented beef heart submitochondrial particles was studied by electron paramagnetic resonance in conjunction with the spin trap 5,5'-dimethyl-1-pirroline-N-oxide (DMPO). Supplementation of submitochondrial particles with NADH or succinate in the presence of antimycin resulted in the formation hydroxyl-, alpha-hydroxyethyl-, and methyl radical adducts. The latter two adducts were derived from HO. attack of ethanol or dimethyl sulfoxide (DMSO), respectively, the solvents used for the inhibitors of the respiratory chain. These ESR signals were slightly increased by superoxide dismutase and abolished by catalase. Further support for the production of HO. during mitochondrial electron transfer was furnished by kinetic competition experiments with DMSO as the HO. scavenger. This approach yielded a kappa SCAVENGER/kappa DMPO value of 1.7, in agreement with a competitive spin trapping of free HO. using DMSO as a scavenger. The scission of H2O2 to HO. requires consideration of a Fenton chemistry, i.e., the participation of metals or redox active metal pools in mitochondria to drive this reaction. The effect of several metal chelators on the formation of both HO. and H2O2 was examined. Bathophenantroline, bathocuproine, and desferrioxamine decreased the DMPO-HO. signal and increased accumulation of H2O2. Conversely, EDTA or diethylenetriaminepentaacetic acid substantially increased the DMPO-HO. signal intensity and decreased H2O2 accumulation. These different results were rationalized in terms of the reduction potential of the redox couples involved, i.e., that of the ligated metal and those encompassed in the one-electron reduction of superoxide radical and of hydrogen peroxide. The formation of 8 hydroxydesoxyguanosine in mitochondrial DNA was examined under experimental conditions in which H2O2 production by isolated mitochondria was enhanced. The formation of 8-hydroxydesoxyguanosine increased with increasing rates of H2O2 formation. The biological significance of H2O2 and HO. formation during mitochondrial electron transfer is discussed in terms of oxidative damage of mitochondrial DNA and the implications for mitochondrial functions and aging. PMID- 7864651 TI - Structural characterization of argingipain, a novel arginine-specific cysteine proteinase as a major periodontal pathogenic factor from Porphyromonas gingivalis. AB - Argingipain, so termed due to its peptide cleavage specificity at arginine residue, is a unique extracellular cysteine proteinase produced by the anaerobic rod Porphyromonas gingivalis, which is known as a major pathogenic factor of the progressive periodontal disease (T. Kadowaki, M. Yoneda, K. Okamoto, K. Maeda, and K. Yamamoto (1994) J. Biol. Chem. 269, 21371-21378). The catalytic specificity and functional importance of this enzyme prompted us to elucidate its structural features. A DNA fragment for argingipain was selectively amplified by polymerase chain reaction using mixed oligonucleotide primers designed from the NH2-terminal amino acid sequence of the purified enzyme. Although the extracellular mature enzyme was shown to have an apparent molecular mass of 44 kDa in gels, the nucleotide sequence of the isolated gene revealed a single gene coding for a 109-kDa precursor of argingipain. The deduced amino acid sequence exhibited no significant similarity to the sequences of representative members of the cysteine protease family. The precursor contained four functional domains: the NH2-terminal signal peptide required for the inner membrane transport; the NH2-terminal prosequence, which is assumed to stabilize the precursor structure; the proteinase domain; and the COOH-terminal hemagglutinin domain, which appears to be essential for extracellular secretion of the proteinase domain. Experiments involving the addition of the argingipain inhibitors to the culture medium of P. gingivalis suggested that the maturation of argingipain occurs intracellularly via an autocatalytic cleavage of the pro-argingipain propeptide. PMID- 7864652 TI - Recombinant expression and evaluation of the lipoyl domains of the dihydrolipoyl acetyltransferase component of the human pyruvate dehydrogenase complex. AB - The subunits of the dihydrolipoyl acetyltransferase (E2) component of mammalian pyruvate dehydrogenase complex (PDC) associate to form a large inner core with a protruding structure composed of three globular domains connected by mobile linker regions. This exterior region of E2 includes two lipoyl domains which engage not only in the intermediate reactions of the complex but also have integral roles in the kinase-phosphatase regulatory interconversion of the pyruvate dehydrogenase (E1) component. To facilitate understanding of these roles, lipoyl domain constructs of the E2 component of human PDC were expressed as glutathione S-transferase (GST)-linked fusion proteins from plasmid inserts prepared by polymerase chain reaction procedures. The NH2-terminal lipoyl domain, E2L1, and the interior lipoyl domain, E2L2, are connected by a 30-amino-acid hinge region, H1. Constructs designed and expressed were E2L1(1-98), E2L1.H1(1 128), E2L2(120-233), E2H1.L2(98-233), and E2L1.H1.L2(1-233), where numbers in parentheses give the amino acid sequence for the portions of the E2 component incorporated into a construct. The domains were expressed in Escherichia coli with and without lipoate supplementation. GST constructs were purified to homogeneity by affinity chromatography and selectively released by thrombin treatment. Sequencing of insert DNAs and NH2-terminal sequencing confirmed that domains were produced as designed. Measurement of masses by electrospray mass spectrometry indicated that constructs with lipoylated, nonlipoylated, and octanoylated forms were produced when expression was with E. coli grown without lipoate supplementation and that fully lipoylated forms were produced upon lipoate supplementation. The lipoylation status was confirmed, following delipoylation with Enterococcus faecalis lipoamidase, by the expected decrease in mass and by the observation in native gel electrophoresis of a shift to a slower mobility (possibly less compact) form. Constructs were used in E1-catalyzed reductive-acetylation reaction in proportion to their degree of lipoylation and were effective substrates in a NADH-dependent dihydrolipoyl dehydrogenase reduction reaction. Thus, we have produced lipoyl domain constructs that can be employed in sorting the specific roles of E2L1 and E2L2 in facilitating catalytic and regulatory processes. PMID- 7864653 TI - Glutathione depletion in rested and exercised mice: biochemical consequence and adaptation. AB - The effect of chronic in vivo glutathione (GSH) depletion by L-buthionine-[S,R] sulfoximine (BSO) on intracellular and interorgan GSH regulation was investigated in mice both at rest and after an acute bout of exhaustive swim exercise. BSO treatment for 12 days decreased concentrations of GSH in the liver, kidney, quadriceps muscle, and plasma to 28, 15, 7, and 35%, respectively, compared to GSH-adequate mice. In most tissues, with the exception of the kidney, this decrease was associated with a concomitant decrease of glutathione disulfide (GSSG) such that the GSH/GSSG ratio was maintained. GSH depletion caused adaptive changes in several enzymes related to GSH regulation, such as liver glutathione peroxidase (-25%), kidney gamma-glutamyltranspeptidase (+20%), glutathione disulfide reductase (+131%) and glutathione sulfur-transferase (+53%). There was an apparent down-regulation of muscle gamma-glutamyltranspeptidase (-56%) in the GSH-depleted mice, which contributed to a conservation of plasma GSH. Exhaustive exercise in the GSH-adequate state severely depleted GSH content in the liver ( 55%) and kidney (-35%), whereas plasma and muscle GSH levels remained constant. However, exercise in the GSH-depleted state exacerbated GSH deficit in the liver (-57%), kidney (-33%), plasma (-65%), and muscle (-25%) in the absence of adequate reserves of liver GSH. Hepatic lipid peroxidation increased by 220 and 290%, respectively, after exhaustive exercise in the GSH-adequate and -depleted mice. We conclude that GSH homeostasis is essential for the prooxidant antioxidant balance during prolonged physical exercise. PMID- 7864654 TI - Three-dimensional reconstruction of Sepia officinalis hemocyanin from frozen hydrated specimens. AB - The three-dimensional reconstruction of Sepia hemocyanin from randomly oriented native molecules was carried out by the method of the random conical tilt series on a frozen-hydrated specimen. As other molluscan hemocyanins, the molecule resembles a hollow cylinder or pentahedron composed of five dimeric subunits. Each dimeric subunit, composed of 16 functional units, comprises one wall oblique unit made up of 12 functional units and one arch made up of four functional units. The five wall oblique units are separated from each other by five oblique clefts bridged by the five arches, formerly termed collar structures. Each arch is composed of two types of functional units that are probably Soe, a functional unit absent in Octopus hemocyanin, and Soh, the C-terminal functional unit of the polypeptide chain. The architecture of the arches and their intramolecular location in front of the edges of the pentahedron are strongly reminiscent of the arches of Octopus hemocyanin. The D5 point-group symmetry of the molecule suggests that the orientation of the polypeptide chains is antiparallel as in Octopus hemocyanin. Several models of architecture compatible with these results are designed. PMID- 7864655 TI - Ehlers-Danlos syndrome type VII: phenotype and genotype. AB - A patient suffering from a severe form of Ehlers-Danlos syndrome is presented (EDS type VII). The presence of bilateral congenital hip dislocation, generalized joint hypermobility and a soft hyperelastic skin with abnormal scarring suggested a specific collagen type I defect. SDS-PAGE analysis of collagens secreted into the medium of fibroblast cultures showed a retarded migration of more than half of the alpha 2(I) chains. CNBr peptide mapping of the HPLC-purified altered chain localized the mutant locus to the N-terminal region of the protein. cDNA analysis of the corresponding gene COL1A2 revealed, in addition to the expected collagen sequence, a transcript missing the entire exon 6. This exon encodes a major crosslinking site within collagen fibres as well as the N-propeptidase cleavage site. The skipping of exon 6 is caused by a splice site mutation substituting an A for a G at the first nucleotide of intron 6. PMID- 7864656 TI - Lichen sclerosus et atrophicus. A histological, immunohistochemical and electron microscopic study. AB - We studied three cases of genital lichen sclerosus et atrophicus (LSA) using histological, immunohistochemical and ultrastructural techniques to elucidate the characteristics of the collagen fibres, the elastic fibres and the interfilamentous matrix in the upper dermal homogeneous zone. In the early stages of LSA, the homogeneous zone caused elaunin fibres to push downwards and partially disappear, the collagen fibres were presumably phagocytosed by fibroblasts, and there were peculiar cells containing numerous vacuoles in the cytoplasm. In the advanced stages of LSA, the homogeneous zones showed newly formed collagen fibres and amorphous, dispersed, medium electron-dense substances that were probably composed of elastin or elastin-like substances and microfilaments originating from the collagen fibres. Immunohistochemically, there were numerous anti-aortic alpha-elastin-positive substances, but there was no positivity for anti-amyloid P component. These findings suggest that in advanced LSA a hybrid substance (elastocollagenous mass) between collagen fibres and elastic fibres may be formed in the homogeneous zone. PMID- 7864657 TI - all-trans-retinoic acid preserves viability of fibroblasts and keratinocytes in full-thickness human skin and fibroblasts in isolated dermis in organ culture. AB - Human dermal fibroblast and human epidermal keratinocyte survival was examined under various conditions in organ culture. Using cell recovery from organ cultured tissue as the criterion, it was observed that no keratinocytes and few fibroblasts survived incubation for 10-12 days in serum-free basal medium containing a low level (0.15 mM) of extracellular Ca2+. Increasing the extracellular Ca2+ concentration to 1.4 mM or treating the tissue with 3 microM retinoic acid (RA) under low Ca2+ conditions resulted in increased keratinocyte and fibroblast survival; the two treatments together were more effective than either treatment alone. The same treatments preserved fibroblast survival when pieces of isolated dermal tissue were incubated in organ culture and also supported fibroblast survival in monolayer culture. These findings indicate that recovery of keratinocytes and fibroblasts from skin after maintenance in organ culture provides a simple but definitive measure of the viability of the major cellular elements present in the tissue. These findings suggest that RA treatment enhances survival of both fibroblasts and keratinocytes and that these effects of RA can be seen at physiological Ca2+ concentrations as well as at suboptimal levels of extracellular Ca2+. Finally, these results indicate that the dermis is a direct target of RA. PMID- 7864658 TI - Immunoelectron microscopic localization of fibronectin in cultured human keratinocytes. AB - We investigated the ultrastructural localization of fibronectin (FN) in cultured human keratinocytes using an improved method of peroxidase-immunoelectron microscopy. This method enabled us to visualize the precise localization of FN within the cells while preserving the morphology. FN was localized in the protein synthetic and secretory organelles, including the rough-surfaced endoplasmic reticulum, Golgi complex, multivesicular bodies and perinuclear space. It was also detected in the extracellular space, on small regions of the villous projections of cell membranes at the site of secretion and at cell-substratum contact sites. These findings confirm that human keratinocytes synthesize, secrete and deposit FN in the pericellular matrix. PMID- 7864659 TI - Lysophosphatidylcholine: a chemoattractant to human T lymphocytes. AB - Various cell stimuli act through activation of phospholipase A2 resulting in the release of arachidonic acid, the precursor of eicosanoids, from the sn-2 position of cell membrane phospholipids. A byproduct of phospholipase A2 activity is the lysophospholipids which have been found to potentiate T-lymphocyte activation. The purpose of the present study was to determine whether the various lysophospholipids modulate the migration of peripheral normal human T lymphocytes in vitro. It was found that lysophosphatidylcholine (lysoPC) induced T-lymphocyte migration in the concentration range 10(-7) to 10(-4) M with a maximum at 10(-6) M (mean chemotactic index, 2.06). The migration was due to chemotaxis rather than chemokinesis. In contrast, lysophosphatidylethanolamine (lysoPE) and lysophosphatidylinositol (lysoPI) did not exhibit chemotactic properties towards T lymphocytes. Further studies showed that the length of the fatty acids in the sn-1 position as well as the presence of double bonds modulated the chemotactic ability. The lysoPC compound with the highest chemotactic activity was lysoPC;1 palmitoyl (C = 16:0). The results demonstrated that lysoPC, a phospholipase A2 generated hydrolysis product of phosphatidylcholine, induced T-lymphocyte chemotaxis in vitro. Because phosphatidylcholine is the major phospholipid in the epidermis, the activation of phospholipase A2 may result in the release of lysoPC in concentrations capable of inducing migration of T lymphocytes into the epidermis. PMID- 7864660 TI - Effect of various metals on intercellular adhesion molecule-1 expression and tumour necrosis factor alpha production by normal human keratinocytes. AB - Nickel, cobalt and chromium are metals very often implicated in allergic contact dermatitis. In vivo, keratinocytes, which are the first target cells, can be directly activated to participate in the local reaction, especially through the expression of the membrane antigen ICAM-1, a ligand of the leucocyte antigen LFA 1, and the production of cytokines. Our aim was to assess the effects of sensitizing metal haptens (nickel, cobalt and chromium) compared with the toxic metal cadmium on the induction of ICAM-1 and the production of TNF alpha by epidermal cells. For this purpose, normal human keratinocytes obtained during plastic skin surgery were cultured in low-calcium defined medium (MCDB153) and the metals were used in non-toxic concentrations. Using FACS analysis, ICAM-1 expression was found to be induced only by nickel. This stimulation appeared as early as 24 h after stimulation. All the metals induced a low expression of TNF alpha detectable by immunocytochemistry correlating with the induction of the nuclear stress protein Hsp72 which is closely linked genetically with the TNF alpha locus. However, only Ni2+, Co2+ and Cr2+ induced a significant release of TNF alpha detectable by ELISA after 48 h stimulation. This secretion was lower than that observed with known stimulants such as lipopolysaccharide. These results indicate that the metals studied are able to induce an aggressive cellular effect, and that nickel, by its ICAM-1 induction, may play a major role in the keratinocyte activation state during allergic contact dermatitis. PMID- 7864661 TI - Human growth factor (huGRO), interleukin-8 (IL-8) and interferon-gamma-inducible protein (gamma-IP-10) gene expression in cultured normal human keratinocytes. AB - HuGRO, IL-8 and gamma-IP-10 belong to a recently described superfamily of genes encoding a group of cytokines with inflammatory, growth regulating and/or leukocyte chemotactic properties (chemokines). We studied huGRO, IL-8 and gamma IP-10 gene expression in unstimulated and stimulated (TNF alpha, INF gamma, TNF alpha + IFN gamma, IL-1 beta, PMA and LPS) normal human keratinocytes by Northern blot analysis. The mRNA for none of the three chemokines was detectable in unstimulated keratinocytes, but considerably elevated levels of huGRO and IL-8 mRNA, but not of gamma-IP-10 mRNA, were found in the presence of cycloheximide, indicating that huGRO and IL-8 mRNA, but not gamma-IP-10 mRNA, are constitutively produced. gamma-IP-10 mRNA was exclusively induced by IFN gamma, with a strong and transient rise between 8 and 18 h, and superinduced by the combination of IFN gamma and TNF alpha, indicating marked synergism. Both huGRO and IL-8 mRNA were induced by TNF alpha and PMA (a strong and transient rise between 2 and 8 h), but not by IFN gamma or LPS. The combination of TNF alpha and IFN gamma did not show a synergistic effect. In addition, IL-1 beta transiently upregulated huGRO mRNA but failed to induce IL-8 mRNA. Using specific oligonucleotides for alpha, beta and gamma huGRO, TNF alpha was found to induce all three forms, alpha and beta to an equal extent and gamma to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864663 TI - Protective effect of some exogenous glycolipids on human cultured keratinocytes against lipid peroxidation. AB - Cultured human keratinocytes were incubated in the presence of glycolipids (GM1, asialoGM1, glucosylceramide and galactosylceramide) added to the medium at a concentration of 10(-5) M. All of them became associated with the cells, but in different amounts depending on the type of glycolipid and on the time in culture. GM1- and asialoGM1-treated keratinocytes developed a resistance to peroxidative stress induced by FeSO4/H2O2 treatment. These results suggest that these exogenously added glycolipids could play a role as eutrophic, repairing and protective agents for the epidermis. PMID- 7864662 TI - Changes in oncogene mRNA expression during human keratinocyte differentiation. AB - The nuclear proto-oncogenes are involved in transcriptional regulation and control many cell processes. The role of changes in proto-oncogene expression in controlling the balance between proliferation and differentiation was studied in cultured keratinocytes. Normal human keratinocytes were grown in the serum-free medium MCDB153 with an extracellular calcium concentration of 70 microM. After treatment with different differentiation conditions, cellular RNA was size fractionated on agarose gels and transferred to nylon membranes which were subsequently hybridized with c-myc, c-jun, and H-ras 32P-labelled probes. Relative RNA loading was assessed using probes for beta-actin and ribosomal 18s RNA. Inducing differentiation by increasing the calcium concentration of the medium from 70 microM to 1.5 mM resulted in a marked decrease in c-myc RNA levels to 26% of control levels within 8 h. After 48 h in 1.5 mM calcium, c-myc levels had recovered to approximately 50% of control levels. There was a gradual reduction in c-jun levels to 56% of control levels by 4 days. Treatment with 10 nM TPA, which also induces keratinocyte differentiation, reduced c-myc RNA levels to 70% of control levels during the first 4 h, but thereafter c-myc levels remained approximately constant for a further 20 h. TGF beta (2 ng/ml), which inhibits keratinocyte growth without inducing differentiation, did not alter c myc RNA levels over a 4-day period. There were no changes in c-myc levels following the addition of retinoic acid and none of the conditions altered H-ras levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864664 TI - UVA- and UVB-induced changes in hairless mouse skin collagen. AB - UVA- and UVB-induced alterations in dermal collagen were investigated in a murine animal model. Groups of hairless mice were exposed to UVA and UVB for 28 weeks at a dose of 60 J/cm2 three times weekly and 0.06 J/cm2 three times weekly, respectively. Untreated animals were used as controls. Every 4 weeks dorsal skin was examined for quantitative and qualitative changes in dermal collagen. Neither UVA nor UVB caused a significant alteration in total skin collagen content. However, after UVA treatment the ability of skin collagen to be digested by pepsin decreased dramatically (up to 65% of skin collagen remained insoluble after 4 months), whereas exposure to UVB had no significant effect. Furthermore a shift in the ratio of alpha 1(I,III) chains to alpha 2(I) chains was detected after UVA exposure. The amount of type V collagen in mouse skin, as determined by a sensitive ELISA method, was markedly decreased after UVA treatment, but not after UVB treatment. PMID- 7864665 TI - Validation of an in vivo extraction method for human stratum corneum ceramides. AB - A topical acetone/diethylether (A/E) lipid extraction method was evaluated for its suitability for use in the study of stratum corneum lipids in various skin disorders. Its efficiency was compared in vitro with topical chloroform/methanol (C/M) extraction and with the classical 'integral' C/M extraction (submerged tissue) of stratum corneum or whole epidermis. To estimate the depth of lipid removal by A/E extraction, light microscopic and freeze-fracture electron microscopic studies were carried out on A/E and C/M topically treated skin samples. The in vivo experiments consisted of topical A/E extraction and of classical C/M extraction of scrapings of the stratum corneum. Transepidermal water loss (TEWL) was measured before and after topical A/E extraction and after every scraping procedure, and correlated with TEWL values found after stripping of the stratum corneum. The total amount of lipid found with both topical extraction procedures was lower than that found with the integral extraction of the stratum corneum. Light microscopy showed that topical C/M extraction induced cell damage in the living epidermal cell layers. Great interindividual variation in overall lipid composition was shown in the in vitro experiments irrespective of the extraction protocol used. However, the ceramide (CER) profiles in a single skin sample from the same subject were similar irrespective of the protocol used, and a uniformity in the CER profiles was found in skin samples from different subjects. Similar results were obtained with in vivo topical A/E extractions: marked interindividual variation was seen in overall lipid composition, but not in the CER profile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864666 TI - Immunohistochemical detection of cyclin D and cyclin A in human hyperproliferative epidermis. PMID- 7864667 TI - [Comparative sensitivity of intravenous urography, ultrasonography and DMSA scan in the diagnosis of vesicoureteral reflux nephropathy]. AB - We compared the efficiency of the IVP, the ultrasound and the DMSA scan in the detection of pyelonephritic lesions during the evaluation of 165 kidneys in 83 children, aged up to 14 years, with vesicoureteric reflux. Our study showed an efficiency of 60.20% for the IVP, 29.60% for the ultrasound and 96.90% for the DMSA scan. These results clearly show that the best imaging method for detecting renal scars is the DMSA scan, followed by IVP and ultrasound. PMID- 7864668 TI - [Reconstructive surgery in complex hypospadias: therapeutic indications and technical considerations in 93 cases]. AB - Perineo-scrotal hypospadias and the severe sequelae of a failed repair procedure are complicated cases. The present study describes our experience in the treatment of complex hypospadias, the new therapeutic possibilities, their indications and results. From 1981 to 1992, 93 children with complex hypospadias underwent surgery (53 underwent surgery for the first time and 40 for severe sequelae of a failed procedure). Excellent cosmetic results were achieved by surgery. For those undergoing hypospadias repair for the first time, we used a pedicled preputial flap following the Duckett (12 cases) or Standoli (41 cases) technique. For those with severe sequelae from a failed procedure, we utilized a pedicled skin flap (18 cases) or free flap of bladder mucosa or penile skin (22 cases). The overall complication rate was 50% (47 patients). Surgical repair of complex hypospadias is a relatively long and complicated procedure with a long learning curve and a high complication rate in the initial phase. Fistula is the most common complication, although closure is very simple due to the abundant, well vascularized, healthy tissue. Overall our results have been satisfactory, considering the severity of these cases. PMID- 7864669 TI - [Transrectal echography in tuberculous prostatitis]. AB - Tuberculous prostatitis is diagnosed incidentally, when the pathologist is studying a specimen of transurethral resection of the prostate or a prostatic biopsy. There is scant literature on the role of transrectal ultrasound in the diagnosis of this pathology. A case of tuberculous prostatitis is presented, with special reference to the transrectal ultrasound pattern. A complete review of the references on the imaging techniques in this pathology is done. PMID- 7864670 TI - [Renal infarction following pulmonary surgery in a 13-year-old boy]. AB - We report a case of renal polar infarction in a 13-year old boy following surgical excision of contralateral congenital lobar emphysema. Patient history was unremarkable and yielded no data suggestive of any other underlying pathology or systemic disease. The diagnosis was made on the CT, arteriography and DMSA scan findings. The etiology could not be determined. The patient was treated conservatively with prophylactic antibiotic therapy and followed closely. There were no complications; the patient was asymptomatic one month after the episode. The control IVP showed residual segmental atrophy and ultrasound evaluation disclosed cortical atrophy. The most common cause of this condition, the diagnostic algorithm, treatments and their indications are discussed. Renal graft infarction, which may be associated with acute rejection or venous and/or arterial thrombosis, warrants special attention. The treatment and clinical course are significantly different, although the diagnosis is made using the same methods. PMID- 7864671 TI - [Inverted Y ureteral duplication]. AB - We report a case of inverted Y duplication of the ureter, incidentally found in a man consulting for hematuria. The diagnostic and therapeutic aspects are briefly discussed. PMID- 7864672 TI - [Lethality of prostatic origin]. AB - We report a case of cutaneous metastasis originating from prostate adenocarcinoma. We underscore this rare site of metastasis and the poor outcome. PMID- 7864673 TI - [Simultaneous renal cell carcinoma and transitional cell carcinoma of the bladder. A case report]. AB - Herein we describe a case of renal cell carcinoma at the base of a giant right renal cyst coexisting with transitional cell carcinoma. The humoral, radiographic, endoscopic and CT findings are presented, as well as treatment and the results achieved at one year follow-up. PMID- 7864674 TI - [Chronic hemorrhagic pyelonephritis simulating renal carcinoma. A case report]. PMID- 7864675 TI - Vesicovaginal fistulas: our experience and review of literature. AB - Vesicovaginal fistulas (VVF) still represent a sad complication of surgery of the female genital system. In this article an extensive review of the literature was conducted, analyzing the etiological, pathological and clinical aspects, as well as the therapeutical problems. For this purpose, we have compared the many surgical techniques proposed for treatment of VVF and have also evaluated their results. Furthermore, we report on our series of 35 patients who had undergone treatment for VVF. PMID- 7864676 TI - [Experimental bladder augmentation with Gore-tex amine: biomechanical, biochemical and biostructural aspects]. AB - We conducted an experimental study on 20 dogs that were subdivided into two groups: the control group comprised 5 dogs that were submitted to resection of 50% of the bladder; the other group comprised 15 dogs submitted to resection of 50% of the bladder and replacement with Gore-tex patch, which was removed 3 months thereafter in 10 dogs. CPK, creatinine, ions, and urinary pH values were determined and urine cultures were performed. The biomechanical parameters of the bladder wall were determined by cystometry. A histological study with hematoxylin eosin of bladder dome specimens was done. The results showed no increased bladder capacity in the animals that received the Gore-tex implant versus the control animals, chiefly due to the necrosis produced by stiffness of the Gore-tex implant. This necrosis was associated with diminished elasticity (due to collagen) and substitution of the muscle fibers by other viscoelastic fibers with a higher elastic constant. Three months following removal of the Gore-tex implant, we observed fibrotic reaction, secondary calcification of the necrotic bladder wall and inflammatory phenomena that impeded muscle regeneration. The urinary pH increased significantly in the dogs that received the Gore-tex implant. The foregoing results show that although the Gore-tex patch is impermeable and resistant to infection, it does not have the appropriate biomechanical properties. PMID- 7864677 TI - ["Supreme" dressing in the prevention of hematoma and edema in scrotal surgery]. AB - An efficient compression can reduce the complications of an inadequate hemostasis following scrotal surgery. The main difference between the "sumo" and previously described compressive methods lies in the use of both pelvic brims as main loading points for the dressing. Similar features are provided by standard scrotal supports but the compression they are able to achieve is minimal compared to that of "sumo" dressing. PMID- 7864678 TI - [Acquired enterovesical fistulas]. AB - We report on 23 patients with acquired vesicoenteric fistula treated during the past 12 years: 48% of these were of inflammatory etiology (11 cases), 35% were caused by neoplasms (8 cases) and 17% were iatrogenic (4 cases). The most frequent symptoms were pneumaturia and fecaluria (78% of cases). Cystoscopy was the most useful diagnostic procedure in detecting fistula (13 of 18 cases). Other imaging techniques, though less effective for diagnosis, were useful in assessing the status of the GI tract and, at times, in determining the etiology of the fistulae. Treatment depends on the etiology, localization and patient general condition. The technique most frequently applied in our series was resection of the fistulous tract, together with the compromised intestinal segment, and bladder suture. PMID- 7864679 TI - [Serum and tissue quantification of tissue polypeptide antigen (TPA) in transitional cell carcinoma of the bladder]. AB - Tissue polypeptide antigen (TPA) is a marker of proliferative cellular activity. The aim of this paper is to demonstrate the production of this marker in bladder carcinomas and to study the biological behaviour in this type of patients. From September, 1992 to June, 1993, we studied 50 patients divided into two groups. The first group comprised healthy subjects and the second one comprised 30 patients with bladder carcinoma. In both groups, we determined the TPS in blood and tumoral tissue by RIA (TPS-IRMA Beki-Diagnostic AB). Our results demonstrated higher levels of TPS in tumoral tissue and blood than in healthy subjects (1887.83 and 197.33 vs 231.5 and 58.23 IU/ml) and higher levels of tissular and blood TPS for the undifferentiated tumors (989.66 and 231.5, 1748.2 and 210, 1842.6 and 219, 2010.7 and 220 IU/ml for Broders' classification 1, 2, 3 and 4). PMID- 7864680 TI - [Prostate-bladder rhabdomyosarcoma: therapeutic approaches]. AB - We describe the unusual case of a young male who presented lower urinary tract obstruction secondary to a bladder-prostate embryonal rhabdomyosarcoma. Initially he was treated with multiagent chemotherapy and radiotherapy in an attempt to preserve bladder function, but eventually radical cystoprostatectomy was warranted to control tumor growth. The objectives of chemotherapy and radiotherapy, partial and/or radical surgery and the main prognostic factors are briefly discussed. PMID- 7864681 TI - [Lymphomas of the urogenital system. Review of the entirety and report of 2 cases with testicular localization]. AB - Lymphomas comprise a group of diseases of the lymphoreticular system arising from any of the cellular elements of lymph nodes, but they can also affect other organs or systems such as the urogenital system. This is the normal process, but there exist some diseases diagnosed as lymphomas within the urogenital system with no evidence of generalized involvement that are classified as primary lymphomas. We analyzed the different urogenital tract organs that may be affected, with special reference to the most interesting aspects of this pathology. Furthermore, two cases of testicular lymphoma are described. In one of them, testicular involvement was the presenting feature of lymphomatosis. The other case was a patient with a diagnosed prostatic adenocarcinoma. The diagnosis was made on the pathological findings of the orchidectomy specimen. The outcome was poor in both cases. PMID- 7864682 TI - [Multivariate analysis of the impact of surgical complications in renal transplant]. AB - We analyzed 307 cadaver kidney transplantations performed since 1976 at the University Hospital of the University of Navarra. Two series, the historical and the current one, are presented. In the former, cyclosporine A was not included in the immunosuppressor protocol. The surgical complications were evaluated in both series and their influence on the survival of the allograft. The current series showed a significant decrease in surgical complications. Allograft survival in the historical series was influenced by surgical complications in general, and vascular and other complications in particular. The current series was influenced by surgical complications in general, and urinary and vascular complications in particular. The multivariate analysis showed that surgical complications were one of the most important prognostic factor in both series. PMID- 7864683 TI - Curing lupus--views from the foothills. PMID- 7864684 TI - Genetic anticipation and musculoskeletal disease. PMID- 7864685 TI - Genetic aspects of familial osteoarthritis. PMID- 7864686 TI - Persistent pulmonary lesion in a patient with rheumatoid arthritis. PMID- 7864687 TI - Sociodemographic factors and the outcome of rheumatoid arthritis in young women. AB - OBJECTIVE: To investigate the impact of sociodemographic factors on the outcome of rheumatoid arthritis (RA). METHODS: A group of 138 women with RA of recent onset and a mean duration of follow up of 5.8 years was studied. Additional information on sociodemographic variables at disease onset (level of formal education, marital status and employment status) was related to the initial disease severity and various outcome measures. RESULTS: Patients with lower levels of education showed a trend towards a worse outcome, according to Health Assessment Questionnaire (HAQ) score, erosion score and the patient's and physician's assessment of outcome at the last visit. However, we also found a trend towards an association between lower levels of education and more severe disease at onset, as measured by HAQ score, erosion score and the number of painful and swollen joints. The association between lower levels of education and poorer outcome of RA was weakened after correction for the initial disease severity. Results of other sociodemographic variables were equivocal. CONCLUSIONS: Differences in severity of RA between patients with different levels of education develop or are present in the early stages of the disease. PMID- 7864688 TI - Musculoskeletal disorders and disability in persons aged 85 and over: a community survey. AB - OBJECTIVES: To study the prevalences of musculoskeletal disorders and disability in the elderly, and the relationship between them. METHODS: A community sample of 73 females and 32 males aged 85 and over underwent a standardised examination at home. Musculoskeletal disorders were classified according to published clinical criteria. The relative effects on disability (a walking distance of < 500 m or dependency in activities of daily living (ADL)) of musculoskeletal disorders and comorbidity were analysed by logistic regression. RESULTS: Musculoskeletal pain was reported by 57% of those interviewed. A major restriction of joint movement range was frequent in the shoulder but uncommon in other joints. A shoulder disorder was found in 27% of subjects, rheumatoid arthritis in 1% and osteoarthritis (OA) of the hand, hip, and knee in five, seven, and 18% of subjects, respectively. Disability was frequent: a walking distance of < 500 m was found in 60% and ADL dependency in 40% of the group. Factors related to one or both of these disability measures included female gender, hip and knee OA, impaired vision, cognitive impairment and neurological disease. CONCLUSION: Musculoskeletal pain and disorders, in addition to disability were frequent in this very elderly population. However, as a cause of disability, other disorders were at least as important as musculoskeletal disorders. PMID- 7864689 TI - Outcome of second line therapy in rheumatoid arthritis. AB - OBJECTIVES: To study the functional outcome in patients with rheumatoid arthritis (RA) who tolerate second line drug therapy for five years. METHODS: We enrolled into prospective controlled trials, 190 patients with rheumatoid arthritis who tolerated 'disease modifying' antirheumatic drug therapy for five years. Demographic data were recorded. Disease activity was measured every six months for two years and annually thereafter, using clinical and laboratory variables. Patient function was measured using the modified Health Assessment Questionnaire. The change in each variable was analysed using paired Wilcoxon tests. RESULTS: Patient function improved significantly compared with baseline. The improvement was maximal after one to two years, and thereafter function started to decline slowly. After five years of treatment the patients' function was still significantly better than before treatment had started. There were highly significant improvements in all variables measured to assess disease activity, which remained well controlled throughout the five year period. CONCLUSION: Good control of disease activity and improved function can be achieved long term in approximately 30% of RA patients treated with injectable gold, sulphasalazine or penicillamine. PMID- 7864690 TI - Increment of CD8S6F1 cells in synovial fluid from patients with rheumatoid arthritis. AB - OBJECTIVE: To investigate the role of CD8 cell subsets in the pathogenesis of rheumatoid arthritis (RA) and the phenotypes of T cells adherent or non-adherent to the target cells (endothelial cells and synovial cells) pre-treated with IL-1 beta. METHODS: The expression of S6F1 on CD8 cells and that of an activation marker on CD8 cells and CD8 cell subsets was evaluated in specimens of peripheral blood and synovial fluid obtained from 15 patients with RA and 10 with osteoarthritis (OA) using a two- or three-colour immunofluorescence method for analysis. RESULTS: The percentage of CD8S6F1 cells among CD8 cells in synovial fluid was significantly greater than that of peripheral blood. Synovial fluid from RA patients had a greater percentage of CD8S6F1 cells compared with either peripheral blood of matched patients or synovial fluid of OA patients. The percentage of CD8HLA-DR cells in synovial fluid was markedly greater than that in paired samples of peripheral blood in patients with RA. In the CD8S6F1 cells from both groups of patients, synovial fluid showed an increased percentage of HLA-DR cells compared with peripheral blood. Similar results were observed in CD8 cells lacking S6F1 expression (CD8S6F1-) from both groups of patients. There was no significant difference in the percentage of HLA-DR cells between CD8S6F1 and CD8S6F1- cell populations in peripheral blood. In contrast with peripheral blood, in synovial fluid of RA patients the percentage of HLA-DR cells in the CD8S6F1 cell population was markedly greater than that in the CD8S6F1- population. However, the percentage of HLA-DR cells in both cell populations was similar in synovial fluid of OA patients. In both the endothelial and the synovial cell adhesion assays, the percentage of CD8S6F1 among CD8 cells and the mean fluorescence intensity of S6F1 antigen on CD8S6F1 cells were significantly greater in the adherent T cell population than that in the non-adherent T cell population. CONCLUSION: These results suggest that increased expression of S6F1 antigen and the increased percentage of HLA-DR cells on CD8 cells in synovial fluid may be responsible for the migration of these cells into inflamed synovial tissues, and for cellular interactions between these cells and synovial cells or the extracellular matrix. PMID- 7864691 TI - Cartilage metabolism in the injured and uninjured knee of the same patient. AB - OBJECTIVE: To examine if unilateral knee injury affects the synovial fluid concentrations of aggrecan fragments, cartilage oligomeric matrix protein (COMP) fragments, stromelysin-1, and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the contralateral uninjured knee. METHODS: Synovial fluids from the injured and uninjured knees were obtained at different times in a group of patients after unilateral knee trauma. Serum samples were obtained on the same occasion. Concentrations of aggrecan fragments were determined by precipitation with Alcian Blue; those of COMP fragments, stromelysin-1, and TIMP-1 were measured by immunoassay. Concentrations were compared with those in a reference group of 10 healthy volunteers. RESULTS: Immediately after knee injury, concentrations of aggrecan fragments, COMP fragments, stromelysin-1 and TIMP-1 were increased in the synovial fluid of the injured knee. However, concentrations of aggrecan and COMP fragments, and stromelysin-1 increased also in the contralateral uninjured knee immediately after injury, but less than in the injured knee. Subsequently, the concentrations of all markers decreased in the synovial fluid of the injured knee, but remained unchanged in the uninjured knee. The concentration of aggrecan fragments in the injured knee decreased to less than that in the uninjured knee in the chronic phase. Serum concentrations of COMP were much smaller than those in synovial fluid. CONCLUSIONS: The increased concentrations of aggrecan and COMP fragments and stromelysin-1 in the joint fluid of the contralateral, uninjured knee following unilateral knee injury, compared with concentrations in healthy reference knees, suggest changes in joint cartilage metabolism in both knees following unilateral knee injury. The mechanisms for these changes are unclear. The low serum concentration of COMP makes it less likely that there is any significant 'exchange' of molecular makers between the knees. A further consequence of these findings is that the contralateral knee cannot be recommended as the only control joint in studies of matrix metabolism in patients with unilateral knee injury. PMID- 7864692 TI - Clinical experience with thalidomide in the management of severe oral and genital ulceration in conditions such as Behcet's disease: use of neurophysiological studies to detect thalidomide neuropathy. AB - OBJECTIVE: To examine the efficacy, dose, and safety profile, including neurophysiological testing of thalidomide used in 59 patients (including 23 with Behcet's disease) to treat severe oral or genital ulceration (OGU). METHODS: We identified prospectively subjects (including women of childbearing potential) who had persistent OGU over periods lasting one to 40 years and whose active ulceration was not controlled by other therapies. They were treated with thalidomide. Retrospectively, we identified the number of subjects with complete resolution of the ulcers at one and two months of thalidomide therapy, and the dose required to maintain that improvement in those individuals who relapsed after stopping thalidomide. The decrease from the baseline sensory nerve action potential (baseline SNAP) amplitude value (derived from median, radial and sural nerve SNAPs) at which the development of paraesthesiae was likely to occur was also determined. RESULTS: Complete resolution of the ulcers occurred in 81% of patients within one month of thalidomide therapy at doses of 200 mg/day. No further thalidomide was required by 20% of patients responding and in the remainder improvement was maintained with smaller doses (7-200 mg/day). Using an approximate 50% decrease from baseline SNAP as an indication to discontinue thalidomide, the incidence of symptomatic neuropathy was 13.5%. No patients with a decrease of less than 42% developed neuropathy, and a further 13.5% were asymptomatic with a decrease in SNAP between 42 and 69%. Other side effects were seen in 44% of patients. There were no pregnancies and no requirement for urgent pregnancy testing. CONCLUSIONS: Thalidomide provided a useful therapeutic option in severe oral and genital ulceration which had not responded to other therapies. The physician must remain vigilant to the continuing danger of axonal neuropathy and teratogenesis at all times during thalidomide therapy. PMID- 7864693 TI - Does genetic anticipation occur in familial rheumatoid arthritis? AB - OBJECTIVE: To determine if there is evidence for genetic anticipation in rheumatoid arthritis (RA) by analysing the possibility that parental disease status and age at proband conception influence the age of onset and disease severity of the proband. METHOD: RA outpatients were identified and data were also taken from Newcastle multicase RA pedigrees. Comparisons of age of onset and parental age at proband conception were made for pedigrees grouped according to the disease status of the parents. Correlation coefficients and linear regression models were calculated for the age of RA onset in the probands. Measures of disease severity were compared in RA mother-proband pairs. RESULTS: The results were similar in both the outpatient (n = 153) and multicase pedigree (n = 15) samples. Significant results were confined to pedigrees in which the mother had RA (20 of the outpatient probands and seven of the multicase group). Probands in these sibships had a younger age of RA onset than their affected mothers (38.3 years (95% confidence interval (CI) 33.8 to 42.8) versus 53.7 (47.3 to 60.0) (p = 0.002) in the outpatient sample; 32.4 years (25.3 to 39.6) versus 43.4 years (29.0 to 57.9) (p = 0.1) in the multicase pedigrees). In the maternal RA group, both the maternal and paternal age at proband conception showed significant negative correlations (r = -0.65, p = 0.002 and r = -0.60, p = 0.005, respectively in the outpatient sample) and linear regression coefficients with age of proband disease onset. In seven affected mother-proband pairs, the probands had a tendency to more severe disease, despite shorter disease duration and younger age. CONCLUSIONS: This preliminary analysis has suggested that within pedigrees in which the mother has RA, the features of genetic anticipation and observations consistent with premutation models may prevail. PMID- 7864694 TI - Collagenase in Sjogren's syndrome. AB - OBJECTIVE: To study collagenase production in labial salivary glands in patients with Sjogren's syndrome (SS). METHODS: Collagenases were localised in labial salivary glands by immunohistochemistry. Collagenase activity against triple helical type I collagen monomers in stimulated saliva was measured using sodium dodecyl sulphate polyacrylamide gel electrophoresis and laser densitometry; tissue inhibitor metalloproteinase (TIMP) was measured by enzyme linked immunosorbent assay. RESULTS: Cells containing collagenase of matrix metalloproteinase (MMP)-1 type were more frequent and more intensely staining in SS than in healthy glands. Only SS saliva contained functional enzyme (11.7 (6.8) x 10(-6) IU/1). Cells containing MMP-8 type neutrophil collagenase were not found in situ, which was in accordance with sialochemical findings/doxycycline inhibition studies. TIMP was found in both SS and normal saliva. CONCLUSIONS: Fibroblast, but not neutrophil type, collagenase is synthesised, secreted, and subsequently activated, but is not inhibited by TIMP in labial salivary glands or saliva in SS. Collagenase may destroy glandular and salivary duct tissue and perturb factors influencing the morphogenetic extracellular matrix. PMID- 7864695 TI - Hepatic hypertrophic osteoarthropathy and liver transplantation. PMID- 7864696 TI - Cytokine therapy in rheumatoid arthritis. PMID- 7864697 TI - Antibodies to nuclear antigens in three patients with scleroderma and asthma. PMID- 7864698 TI - Ehlers Danlos syndrome and osteoporosis. PMID- 7864699 TI - Remission of nephrotic syndrome in a patient with renal amyloidosis associated with Takayasu's arteritis after treatment with dimethylsulphoxide. PMID- 7864700 TI - Superficial migratory thrombophlebitis in a patient with reversible protein C deficiency and anticardiolipin antibodies. PMID- 7864701 TI - High blood pressure. A side effect of drugs, poisons, and food. AB - A variety of therapeutic agents or chemical substances can induce either a transient or a sustained increase in blood pressure. These agents increase arterial pressure by either causing sodium retention and extracellular volume expansion or directly or indirectly activating the sympathetic nervous system. Some agents act directly on arteriolar smooth muscle. For certain agents, the mechanism of pressure elevation is mixed or unknown. Paradoxically, some agents that are used to lower arterial pressure may acutely increase arterial pressure. Also, a rebound increase in pressure may be encountered after discontinuation of certain antihypertensive agents. In general, these chemically induced increases in arterial pressure are small and transient; however, severe hypertension involving encephalopathy, stroke, and irreversible renal failure has been reported. Careful evaluation of a patient's drug regimen may identify chemically induced hypertension and prevent the need for evaluation and therapy. This study reviews the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action. PMID- 7864702 TI - Postoperative delirium. A review of 80 primary data-collection studies. AB - We conducted an on-line search and manual searches for 1966 through 1992 to determine the incidence, diagnosis, risk factors, and treatment of postoperative delirium. Of the 374 citations found, 277 articles were excluded after criteria of relevance were applied. After methodologic criteria for validity were applied to the remaining 80 articles, 26 studies were retained for the final information synthesis. The incidence of postoperative delirium was 36.8% (range, 0% to 73.5%). Primary reasons for this disparity were insufficient sample size and inconsistent application of numerous diagnostic tools. One study provided statistically significant data that demonstrated that postoperative delirium is underdiagnosed by physicians and nurses. Four of the articles that met the established criteria provided risk factor data. Although age, preoperative cognitive impairment, and the use of anticholinergic drugs were significantly associated with postoperative delirium, gender, type and route of anesthesia, and sleep deprivation were not. Two studies demonstrated a decreased incidence of postoperative delirium when patients underwent preoperative psychiatric counseling or participated in a structured perioperative program. These findings indicate a need for (1) accurate incidence data with further definition of risk factors and (2) studies that address the diagnosis and treatment of this common postoperative problem. PMID- 7864703 TI - Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. AB - The prevalence of atrial fibrillation (AF) is related to age. Anticoagulation is highly effective in preventing stroke in patients with AF, but the risk of hemorrhage may be increased in older patients. We reviewed the available epidemiologic data to define the age and sex distribution of people with AF. From four large recent population-based surveys, we estimated the overall age- and gender-specific prevalence of AF. These estimates were applied to the recent US census data to calculate the number of men and women with AF in each age group. There are an estimated 2.2 million people in the United States with AF, with a median age of about 75 years. The prevalence of AF is 2.3% in people older than 40 years and 5.9% in those older than 65 years. Approximately 70% of individuals with AF are between 65 and 85 years of age. The absolute number of men and women with AF is about equal. After age 75 years, about 60% of the people with AF are women. In contrast to people with AF in the general population, patients with AF in recent anticoagulation trials had a mean age of 69 years, and only 20% were older than 75 years. The risks and benefits of antithrombotic therapy in older individuals are important considerations in stroke prevention in AF. PMID- 7864704 TI - Short-course ciprofloxacin treatment of acute uncomplicated urinary tract infection in women. The minimum effective dose. The Urinary Tract Infection Study Group [corrected]. AB - BACKGROUND: Three studies were undertaken to determine the minimum effective dosing regimen of ciprofloxacin for the treatment of acute, symptomatic, uncomplicated lower urinary tract infection. METHODS: All studies were multicenter, prospective, randomized, double-blind trials. A total of 970 evaluable patients with a diagnosis of urinary tract infection received oral ciprofloxacin (200 mg to 500 mg daily in one or two divided doses for 1, 3, 5, or 7 days) or norfloxacin (400 mg twice daily [BID] for 7 days). The primary measure of efficacy was bacteriologic eradication at the end of therapy. RESULTS: In study 1, bacteriologic eradication was reported in 95 (89%) and 101 (98%) of patients in the groups who received ciprofloxacin, 500-mg single dose and 250 mg BID for 7 days, respectively. Clinical success occurred in 101 patients (94%) who received a 500-mg single dose and in 103 patients (100%) who were administered 250 mg BID for 7 days. In study 2, eradication rates in the groups who received ciprofloxacin, 100 mg BID for 3 days, 250 mg BID for 3 days, and 250 mg BID for 7 days, were 98 (93%), 95 (90%), and 98 (93%), respectively. Clinical success was reported in 102 (97%), 105 (100%), and 104 (98%) of the patients, respectively. In study 3, the eradication rates in the groups who received ciprofloxacin in dosages of 500 mg once daily for 3 days and 500 mg once daily for 5 days and norfloxacin in a dosage of 400 mg BID for 7 days were 137 (92%), 134 (90%), and 133 (94%) of the women, respectively. Clinical success was the same (97%) in all three groups. Overall, short-course (either 3- or 5-day) therapy with ciprofloxacin was statistically equivalent to conventional (7-day) therapy with either ciprofloxacin or norfloxacin. Single-dose ciprofloxacin therapy was statistically less effective than conventional treatment. CONCLUSIONS: Ciprofloxacin at a dosage of 100 mg BID for 3 days was the minimum effective dose for the treatment of uncomplicated urinary tract infection in women. PMID- 7864705 TI - Magnesium sulfate in exacerbations of chronic obstructive pulmonary disease. AB - BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease are commonly seen and difficult to treat. We sought to determine the bronchodilator efficacy of magnesium sulfate in this situation, as this compound is helpful in acute asthma. METHODS: Subjects who came to either of two Veterans Affairs emergency departments were randomized in a double-blind fashion to receive either 1.2 g of magnesium sulfate or placebo over 20 minutes after they first received albuterol, 2.5 mg by nebulization. Peak expiratory flow, dyspnea scores, arterial hemoglobin oxygen saturation by pulse oximetry, maximal inspiratory and expiratory pressures, and vital signs were monitored for 45 minutes after the start of magnesium sulfate or placebo treatment. RESULTS: Seventy-two individuals were studied. The peak expiratory flow increased 16.6% +/- 27.7% (mean +/- SD) in both groups after the initial albuterol treatment, from 121.2 +/- 55.7 L/min to 136.9 +/- 63.9 L/min. The peak expiratory flow increased from 136.7 +/- 69.7 L/min at the start of the infusion to 162.3 +/- 76.6 L/min at 30 minutes and 161.3 +/- 78.7 L/min at 45 minutes with magnesium sulfate treatment. The peak expiratory flow was 137.0 +/- 58.6 L/min on initiation of the intravenous infusion, 143.0 +/- 72.7 L/min at 30 minutes, and 143.3 +/- 70.5 L/min at 45 minutes in the placebo group. The difference in peak expiratory flow from initiation of the infusion to 30 and 45 minutes later (calculated as means of the 30- and 45-minute values) was significantly different for the two groups (25.1 +/ 35.7 L/min vs 7.4 +/- 33.3 L/min; P = 0.3); the difference was also significant when expressed as percentage increase (22.4% +/- 28.5% vs 6.1% +/- 24.4%; P = .01). There was a statistically nonsignificantly trend toward a reduced need for hospitalization in the magnesium sulfate group as compared with the placebo group (28.1% vs 41.9%; P = .25). There were no significant changes in the other parameters with either treatment. CONCLUSION: Magnesium sulfate, 1.2 g over 20 minutes after beta-agonist administration, is safe and modestly efficacious in the treatment of acute exacerbations of chronic obstructive pulmonary disease, and its bronchodilator effect is greater than that of a beta-agonist given alone and lasts beyond the period of magnesium sulfate administration. PMID- 7864706 TI - Implementation of the patient self-determination act in a hospital setting. An initial evaluation. AB - BACKGROUND: The Patient Self-Determination Act aims to enhance patient awareness of advance directives by requiring health-care institutions to ask patients whether they have advance directives and to inform patients of their rights to prepare these documents. We investigated the following: (1) compliance of the hospital staff with implementing this act, (2) the effects of this act on the extent to which patients discuss and prepare advance directives, and (3) variables that might influence patient discussions on advance planning and preparation of advance directives. METHODS: We surveyed 219 patients from a university hospital that implemented a nurse-dependent advance directive program. We also conducted a telephone interview with 57% of these patients at least 6 months after hospital discharge. RESULTS: Nurses asked 70% of the patients about the existence of an advance directive and of these patients, only 57% remembered the inquiry. Only 57% of the patients received the brochure on advance directives and of these patients, only 55% read the brochure. Only 2% of the patients requested to receive additional information on advance directives. Less than one quarter of the patients had discussions on advance planning while in the hospital and of those patients who were contacted within 6 months after hospital discharge, 39% had discussions on advance planning and 15% prepared an advance directive. Race was an independent predictor for hospital discussions, and educational level was an independent predictor for discussions and preparation of advance directives after hospital discharge. CONCLUSIONS: To enhance the effectiveness of a nurse-dependent advance directive program, hospitals may need (1) to strengthen the quality of the patient-nurse encounter in which the issue of advance directives is raised to more effectively promote patient interest, discussions, and preparation of advance directives and (2) to account for the social diversity of their patient population. PMID- 7864707 TI - Deciding about cardiopulmonary resuscitation. The contributions of decision analysis. AB - BACKGROUND: Patients have the right to decide whether to authorize cardiopulmonary resuscitation (CPR). Physicians should provide adequate information and help clarify preferences. METHODS: The usefulness of decision analysis was investigated in two convenience samples: 20 healthy outpatient volunteers and 35 audience members at medical ethics grand rounds. Subjects quantified their relative preferences (utilities) for the outcomes of cardiac arrest. First, they rated them on a linear scale. Second, they participated in hypothetical gambles in which they indicated how much they would risk to avoid each outcome. The investigator then calculated the overall expected utilities of the CPR and no-CPR strategies. RESULTS: Subjects were able to complete both the gambles and the rating scale. Utilities derived by the two methods differed greatly. Subjects had strong aversions to an outcome of severe long-term brain damage and widely varying ratings of an outcome of a short period of intensive care followed by death (intensive care unit death). Because intensive care unit death is far more likely than long-term brain damage, its utility was the prime determinant of whether CPR or no-CPR had the higher calculated expected utility. CONCLUSIONS: The methods of decision analysis showed promise as a means not only of informing patients about CPR but of helping them make rational choices. They also revealed the inadequacy of current data on the key outcome of intensive care unit death. PMID- 7864708 TI - Appropriate use of heparin. Empiric vs nomogram-based dosing. AB - BACKGROUND: A study involving two groups of patients with cardiovascular disease was conducted to compare empiric (clinician-directed) heparin therapy with therapy based on a nomogram-determined dosage. The comparison was based on (1) the average weight-referenced infusion rate yielding a therapeutic activated partial thromboplastin time (APTT) and (2) the time required to reach a therapeutic APTT (55 to 95 seconds) after empiric or nomogram-based heparin therapy was initiated. METHODS: Data were collected for patients admitted to the cardiology service at a university health science center in two phases: phase 1 (April 1 through June 30, 1992), involving 95 patients receiving heparin therapy, with 88 patients included in the data analysis, and phase 2 (March 11 through June 11, 1993), involving 156 patients receiving heparin therapy, with 45 patients receiving nomogram-guided therapy included in the data analysis. RESULTS: In phase 1, 66 patients (75.0%) achieved a therapeutic APTT some time during their heparin therapy, with an average time to therapeutic APTT of 20.7 + 19.1 hours. Regression analysis demonstrated a statistically significant relationship between the heparin infusion rate at the time of the patient's first therapeutic APTT and the patient's total body weight (r2 = .3043). An initial infusion rate based on total body weight (13 U/kg per hour) was therefore used as the basis for the nomogram in phase 2. In phase 2, 41 patients (91.1%) achieved a therapeutic APTT at some time during their heparin therapy, with an average time to therapeutic APTT of 13.1 + 11.9 hours, statistically significantly shorter than that in phase 1. A greater proportion of patients in phase 2 compared with patients in phase 1 reached the therapeutic range within 12 hours (62.2% vs 34.1%) and within 24 hours (77.8% vs 54.5%). CONCLUSIONS: Use of a weight-based nomogram to determine the initial and maintenance heparin infusion rates was associated with a higher percentage of patients admitted to the cardiology service reaching the targeted therapeutic APTT range at a time earlier in the course of therapy compared with empiric dosing. PMID- 7864709 TI - Amantadine-resistant influenza A in nursing homes. Identification of a resistant virus prior to drug use. AB - BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride have been used for treatment and prevention of influenza A infection in nursing home residents. Outbreaks of influenza A (H3N2) virus infection occurred in three nursing homes in Yakima County, Washington, during January 1992. Amantadine was used for case treatment and prophylaxis in all three nursing homes. METHODS: Ten influenza A (H3N2) viruses isolated during the outbreaks were examined for resistance to amantadine and rimantadine by means of an enzyme immunoassay and by sequencing of the viral nucleic acid that encodes the transmembrane domain of the M2 protein. RESULTS: Five of the outbreak strains were resistant and had the same mutation (position 31, serine to asparagine) in the M2 protein. The resistant viruses included one that had been recovered prior to any use of amantadine and another that was recovered within 48 hours of the first drug administration. CONCLUSIONS: To our knowledge, this is the first report of influenza A virus with RNA sequence documented resistance to amantadine and rimantadine without exposure to either drug, and the shortest reported period between institution of amantadine therapy and isolation of a resistant influenza A virus strain. These results suggest that surveillance for amantadine- and rimantadine-resistant influenza A is needed, because use of these drugs will probably increase. PMID- 7864710 TI - Initial therapy for acquired immunodeficiency syndrome-associated cryptococcosis with fluconazole. AB - BACKGROUND: Published opinion has generally favored amphotericin B over fluconazole as initial therapy for acquired immunodeficiency syndrome-associated cryptococcosis, although data that support this recommendation are limited. METHOD: Retrospective review of 30 consecutive patients with acquired immunodeficiency syndrome-associated cryptococcosis seen at a single institution over a 1-year period and given fluconazole, 400 mg/d, as initial therapy. RESULTS: No patient died within the first 30 days of therapy, and none of the 14 patients who died within 1 year had clinically detectable infection when last seen or at death. Pretreatment blood cultures were positive in 26 of 27 patients; cerebrospinal fluid cryptococcal antigen titer was greater than 1:1024 in 12 of 23 patients; and five of 30 patients presented with altered mental status. The median CD4 count at diagnosis was 0.042 x 10(9)/L (42/microL). Eight of 25 patients who were followed up for more than 30 days relapsed, as evidenced by a positive culture; all relapses were successfully treated with fluconazole, either by reinstitution of therapy or by increase of dosage. CONCLUSION: This experience supports the use of fluconazole as initial therapy for acquired immunodeficiency syndrome-associated cryptococcosis. PMID- 7864711 TI - Doctor-patient communication and medical malpractice: an ambiguous relationship. PMID- 7864712 TI - Neurobiology of cholesterol and violent behavior. PMID- 7864713 TI - Gastric stump carcinoma occurring in a patient with Carney's triad 38 years after partial gastrectomy for epithelioid leiomyosarcoma. PMID- 7864714 TI - Why no advance directive? PMID- 7864715 TI - Use of spacer devices with inhaled steroids. PMID- 7864716 TI - Ambulatory blood pressure monitoring: quality assurance. PMID- 7864717 TI - Heart failure: an update on pathophysiology. AB - Myocardial hypertrophy is an established risk factor for cardiovascular morbidity and mortality. Beyond quantitative and mechanical aspects hypertrophy is associated with alterations in cardiac gene expression, resulting in a more fetal like myocyte phenotype with a fragile Ca++ homeostasis. Depressed expression of sarcoplasmatic reticulum ATPase is the hallmark of this overload phenotype. Conversely, the gene expression and the activity of sodium calcium exchanger is up-regulated in endstage heart failure. Both alterations contribute to prolonged cytosolic Ca++ transients, disturbed relaxation and, probably, to electrophysiologic instability. Angiotensin II is a growth promoting agent and several lines of circumferential evidence suggest that the local formation of angiotensin II might contribute to the trophic response and phenotype shift in cardiac overload. The cardiac gene expression of angiotensin converting enzyme and angiotensinogen is increased early after cardiac overload and in patients with severe heart failure. Chronic ACE inhibition suppresses plasma and tissue ACE activity, reduces LV hypertrophy and improves long-term survival. The hallmark of the peripheral adaptation in chronic heart failure is systemic vasoconstriction, associated with neurohumoral activation. Several mechanisms are involved in the impaired peripheral perfusion, including increased sympathetic tone and increased vascular stiffness. Recently, data suggest an important role of the endothelium for perfusion of skeletal muscle in heart failure. Endothelium dependent dilation of resistance vessels is blunted in patients with severe chronic heart failure. Conceivably, this abnormality may be involved in the impaired reactive hyperemia in patients with chronic heart failure. Moreover, alterations of skeletal muscle emerge in chronic heart failure contributing to reduced exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864718 TI - [Metabolic, morpho-histologic and biochemical changes in skeletal muscles in chronic cardiac failure]. AB - The study of skeletal muscle by nuclear magnetic resonance (NMR) 31p in patients with chronic heart failure (CHF) or in experimental animal models has not shown metabolic abnormalities under basal conditions. However, during exercise, phosphocreatinine (PCr) depletion is increased and early intracellular acidosis has been demonstrated. These changes contribute to deterioration of exercise capacity as they are related to peak VO2 and exercise duration. Other metabolites may play an important role. The depletion of ATP at maximal exercise may be observed in some patients with severe CCF. The results of PCr recovery kinetics are contradictory. Apparently, its recovery rate is unchanged. Most biochemical and histological abnormalities are represented by a decrease in oxidative structure (type I muscular fibres, mitochondria) and in enzymatic oxidative capacity. These changes are related to the metabolic abnormalities and exercise capacity. Muscular hypotrophy alone cannot explain the metabolic changes observed in CHF. Several mechanisms could be involved, physical deconditioning probably being the most pertinent. Other factors such as neurohormonal activation and insulin resistance should be investigated. Physical training improves exercise capacity and may reverse these muscular abnormalities. A long-term benefit of physical training on morbidity and mortality should be demonstrated. PMID- 7864719 TI - [Abnormal peripheral circulation in heart failure]. AB - Left ventricular failure leads to circulatory failure which causes clinical symptoms and in which regional blood flow changes play an important role. An abnormality of systemic vasodilatation on exercise or on pharmacological intervention has been shown. This affects both the resistance and conductive vessels and is mainly functional, related to neurohormonal stimulation with a predominance of vasoconstrictive factors amongst which increased adrenergic tone probably plays an essential part. A modification of the endothelium-dependent response has recently been confirmed. The presence of structural vascular abnormalities (increase in parietal sodium and water concentrations, "remodelling" remains debatable in the human. These abnormalities have a common factor in their chronicity and take time to regress with medical treatment or after cardiac transplantation. Physical training seems to induce more marked and, above all, more rapid effects. PMID- 7864720 TI - Issues concerning the use of angiotensin-converting enzyme inhibitors in the treatment of heart failure and myocardial infarction. PMID- 7864721 TI - [Economic evaluation of treatments of cardiac insufficiency]. AB - The objective of classical treatments of cardiac failure (diuretics, digitalis) was to relieve patients' symptoms. Vasodilators and ACE inhibitors also improve morbidity and mortality. The introduction of the latter class of drugs for cardiac failure will, however, lead to a significant increase in the cost of medication at national level. These costs may increase even further in theory due to a predictable increase in the number of patients with cardiac failure (ageing of the general population, improved survival of cardiac patients) and due to the extension of prescription of these drugs to populations of subjects with cardiac failure hitherto relatively undertreated. On the other hand, economies may be realised in the management of cardiac failure related to fewer and shorter hospital admissions and reduced indirect costs or to the suppression of previous, less useful drugs (calcium antagonists, digitalis). Cost-effective analyses with ACE inhibitors carried out in different countries (Canada, netherlands) tend to show that the costs induced by prescription of these drugs are more than compensated by the economies realised by the reduction in hospital admissions. This is even more marked in the treatment of patients with severe cardiac failure. In subjects at low risk, the prescription of ACE inhibitors would not seem to be justified from both the clinical and economic points of view. It is up to each physician to decide the threshold of basic risk below which this treatment becomes "economically" acceptable. PMID- 7864722 TI - [The ATLAS study (Assessment of Treatment with Lisinopril and Survival); justification and objectives]. AB - Treatment with ACE inhibitors has improved the prognosis of cardiac failure (CF). The results of CONSENSUS I, SOLVD and V HEFT II show clinical improvement and longer survival with this therapeutic class of drugs. However, the search for the optimal dosage was not undertaken in these trials (a standard dose was fixed at the onset, average dose of enalapril from 15 to 20 mg/day). In clinical practice, patients are prescribed lower doses of ACE inhibitors (enalapril: 7.5 mg/day) than the averages used in large scale trials. In order to optimise the use of ACE inhibitors, the ATLAS study (Assessment of Treatment with Lisinopril and Survival) was undertaken with the precise objective of comparing two dosages (2.5 to 5 mg/day vs 32.5 to 35 mg/day) of lisinopril on the morbidity and mortality of patients with CF. This international, multicenter, randomised, double-blind parallel group trial aims to include 3,000 patients over 18 years of age with NYHA Classes II, III and IV, and an ejection fraction < or = 30% and to follow them up for 3 to 4.5 years. Nearly 30 French centres will participate in this trial. After an initial, open period of evaluation of tolerance (5 mg to 15 mg/day of lisinopril in France), the patients will be randomised to two groups. After randomisation, all patients will receive 5 mg per day of lisinopril. The "high dose" group will receive 20 mg/day for two weeks, then 30 mg/day in addition to the "open dosage". In cases of intolerance, the dosage may be reduced to 20 mg/day or 10 mg/day, or the drug may be withdrawn.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864723 TI - An engineer in the medical world. PMID- 7864724 TI - Major contributions to research and development of intracorporeal oxygenators. PMID- 7864725 TI - Intracorporeal oxygenation. AB - The dominant problem in the design of an intracorporeal oxygenator is achieving gas transfer rates sufficient for physiological needs in the space available with acceptably low flow resistance to blood. Design problems still to be solved, when configurations with sufficient gas transfer effectiveness are well identified, are biological tolerance (including adequate blood compatibility), ease of manufacture, and prolonged function. PMID- 7864726 TI - Gas transport in the intracorporeal oxygenator with woven tubes. AB - The woven tubes membrane oxygenator is a suitable configuration for the intracorporeal membrane oxygenator because of a high gas exchange performance and a compact packing of tubing. In this study the oxygen transfer performance of woven tubes was evaluated by an in vitro experiment with an external perfusion mode; the blood flow is outside of the tubes in order to reveal the feasibility of designing the intravascular oxygenator (IVOX) by the woven tubes. The oxygen transfer efficiency of the external perfusion mode is superior to that with the internal perfusion mode because of the larger convective mixing effect on the external surface of the tubes. Thus the use of the external perfusion mode results in the shorter necessary tube length for the rated condition, which enables making the oxygenator unit more compact. All of these features encourage the adoption of the woven tubes for use in the intravascular oxygenator. PMID- 7864727 TI - An intrapleural lung prosthesis: rationale, design, and testing. AB - Extracorporeal life support (ECLS or ECMO) is standard treatment for severe respiratory failure but poses many contraindications to future lung transplantation. The solution to this dilemma is the implantable gas exchange device (IGED) or artificial lung. Preliminary efforts to create such an artificial lung have been made since 1970 and include designs involving single devices, intravascular devices (i.e., IVOX), and combination heart-lung devices. Stringent requirements govern the design of such a device, the most important of which are high gas exchange efficiency, low resistance to blood flow, and size. This paper describes such a device. It incorporates large diameter inflow and outflow ports in close proximity and a low resistance wound hollow fiber core encapsulated in a compliant outer shell which conserves the work of the right ventricle. In a large animal model (adult sheep) this device was connected in line with the main pulmonary artery in series with the native lungs. This configuration has the advantages of using the lungs as an embolic filter, perfusing the lungs with fully oxygenated blood, and maintaining the integrity of the anatomy necessary for transplant. Laboratory experiments have run > 8 h. Preliminary data show that the animals have remained hemodynamically stable while the devices have supported the animals completely by supplying 100% O2 saturation with PO2 values ranging from 250-350 mm Hg. Additionally, this model makes possible the study of respiratory failure without introducing other variables such as extracorporeal circuits or pumps. The other metabolic, endocrine, and reticuloendothelial functions of normal and injured lungs can now be studied more precisely by excluding these variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864728 TI - Development of an intravenous membrane oxygenator: enhanced intravenous gas exchange through convective mixing of blood around hollow fiber membranes. AB - In vitro testing of a new prototype intravenous membrane oxygenator (IMO) is reported. The new IMO design consists of matted hollow fiber membranes arranged around a centrally positioned tripartite balloon. Short gas flow paths and consistent, reproducible fiber geometry after insertion of the device result in an augmented oxygen flux of up to 800% with balloon activation compared with the static mode (balloon off). Operation of the new IMO device with the balloon on versus the balloon off results in a 400% increase in carbon dioxide flux. Gas flow rates of up to 9.5 L/min through the 14-cm-long hollow fibers have been achieved with vacuum pressures of 250 mm Hg. Gas exchange efficiency for intravenous membrane oxygenators can be increased by emphasizing the following design features: short gas flow paths, consistent and reproducible fiber geometry, and most importantly, an active means of enhancing convective mixing of blood around the hollow fiber membranes. PMID- 7864729 TI - Computer-assisted design of an implantable, intrathoracic artificial lung. AB - A semiempirical mathematical model of convective oxygen transport is used to design a new, low pressure loss, implantable artificial lung that could be used as a bridge to lung transplantation in patients with advanced respiratory failure. The mass transfer and flow friction relations pertinent to the design of a cross-flow hollow fiber membrane lung are described. The artificial lung is designed to transfer over 200 ml/min of oxygen at blood flow rates up to 5 L/min. A compact design and a blood-side pressure loss of < 15 mm Hg allows the device to be implanted in the left chest without the need for a prosthetic blood pump. Surgical implantation of the artificial lung would require the creation of inflow and outflow anastomoses. Oxygen would be supplied via an external source. Blood properties, operating conditions, and empirically determined mass transfer and flow properties are all specified and input into a computer program that numerically solves the design equations. Computer-generated values for the device frontal area, blood path length, and fiber surface area are thereby obtained. The use of this computer-assisted design minimizes the need for extensive trial-and error testing of prototype devices. Results from in vitro tests of a prototype implantable lung indicate that the mathematical model we describe is an accurate and useful tool in the design of hollow fiber artificial lungs. PMID- 7864730 TI - Rate of thrombus accumulation on intravenacaval IVOX devices explanted from human clinical trial patients with acute respiratory failure. AB - The weight gain of IVOX devices removed from the first 49 human clinical trials patients after from 1 to 29 days of implantation into the venae caval blood stream has been assessed. Each patient had received sufficient systemic heparin to maintain activated clotting times between 150 and 200 s while the IVOX device was indwelling. The nature of the material accumulating on the IVOX device was documented histologically as being thrombus in various stages of development. The weight gain findings indicate that an average of 2.0 g of thrombus accumulates per 24 h on IVOX devices indwelling in the venous blood stream of moderately anticoagulated human acute respiratory failure patients. The rate of weight gain per 24 h of the IVOX device was more rapid during the first 96 h after its implantation than during its second, third, or fourth week of implantation. The accumulated thrombus on the IVOX hollow fibers was associated with a small but measurable decrease (approximately 1%/day) in gas transfer efficiency of the implanted device. The data support the conclusion that IVOX can function effectively and safely without major thrombus formation for up to 29 days in moderately anticoagulated human acute respiratory failure patients. PMID- 7864731 TI - Late pathophysiologic sequelae after utilization of an intravenacaval oxygenator in experimental animals. AB - The intravenacaval hollow fiber oxygenator (IVOX) has been shown to be remarkably free from acute adverse effects on the venae cavae, right heart, and lungs when indwelling experimentally in sheep and in human clinical trial patients. However, all pathophysiologic assessments reported to date have been carried out during or immediately after IVOX utilization. It is recognized that IVOX indwelling in the venae cavae for up to 3 weeks could produce minor or unrecognized acute injury that could become more evident or more harmful after several weeks had elapsed following removal of the device. Therefore, this current study was designed and carried out to assess any pathophysiologic sequelae that could be recognized on follow-up examination 4 months after removal of an IVOX device that had been indwelling in the venae cavae for from 7 to 13 days. Extensive clinical and physiologic assessments of the blood, hemodynamics, and pulmonary functional status of 8 sheep were carried out 4 months after removal of IVOX devices that had been indwelling for 7 to 13 days. Each animal was then euthanized and complete necropsy examination was conducted looking especially for gross or histologic lesions in the venae cavae, access veins, right heart, and lungs. Findings indicated that all animals were normal, without clinically or pathologically significant pathophysiologic abnormalities or adverse effects from the IVOX utilization. Detailed hematologic, hemodynamic, blood chemistry, pulmonary function, and gross and histopathologic findings, presented in graphic, tabular, and photographic form, document the conclusion that utilization of an IVOX device in normal sheep for from 7 to 13 days produces no significant adverse late pathophysiologic sequelae. PMID- 7864732 TI - Permissive hypercapnia and intravascular oxygenator in the treatment of patients with ARDS. AB - This open clinical study was aimed at testing the hypothesis that an intravascular oxygenator (IVOX) may help to perform permissive hypoventilation in 10 patients with severe ARDS. After initial evaluation, we tried to reduce ventilator settings before and after IVOX implantation. Before IVOX, poor clinical tolerance and worsening oxygenation did not allow for a significant decrease in ventilator settings. With IVOX, peak inspiratory pressure (PIP) was reduced from 47 to 39 cm H2O (p = 0.005) and minute ventilation from 13 +/- 3.5 to 11 +/- 3 L/min. CO2 removal by IVOX allowed a significant decrease in PaCO2 from 66 +/- 15 to 59 +/- 13 mm Hg. Improvement of oxygenation with IVOX was not significant. Furthermore, interruption of oxygen flow through IVOX did not change oxygenation variables. Tolerance of the IVOX device was good, but insertion of the device was followed by a significant decrease in both cardiac index and pulmonary wedge pressure. In conclusion, IVOX improves tolerance of hypoventilation by limiting hypercapnia in ARDS patients. These preliminary results must be confirmed by a randomized controlled study. PMID- 7864733 TI - Intravascular membrane oxygenation and carbon dioxide removal with IVOX: can improved design and permissive hypercapnia achieve adequate respiratory support during severe respiratory failure? AB - The intravenacaval oxygenator and carbon dioxide removal device (IVOX) conceived by Mortensen at CardioPulmonics is a diffusion-limited device capable of removing 30% of CO2 production of an adult at normocapnia with minimal reduction in ventilator requirements. Through mathematical modeling, an ex vivo venovenous bypass circuit to model the vena cava and animal models of severe smoke inhalation injury, the practice of permissive hypercapnia has been established to enhance CO2 removal by IVOX. By allowing the blood PCO2 to rise gradually, the CO2 excretion by IVOX can be linearly increased in a 1:1 relationship. Experimental and clinical studies have shown that CO2 removal by IVOX increased from 30-40 ml/min at normal blood PCO2 to 80-90 ml/min at PCO2 of 90 mm Hg. In addition, IVOX with permissive hypercapnia allowed a significant reduction in minute ventilation and peak airway pressure. Design changes could also improve the performance of IVOX. Increased surface area and mixing with more fibers and crimping in new prototypes of IVOX significantly increased CO2 removal and oxygen transfer. Active mixing in the blood to decrease the boundary layer resistance can further enhance gas exchange of IVOX. In conclusion, gas exchange by the current design of IVOX is limited, and improvements in design are needed for it to become a more clinically applicable device. Permissive hypercapnia can significantly enhance CO2 removal by IVOX as well as significantly reduce ventilator requirements. PMID- 7864734 TI - In vivo gas transfer performance of the intravascular oxygenator in acute respiratory failure. AB - The intravascular oxygenator (IVOX) has undergone both animal and clinical trials. Data from the animal studies have demonstrated that the device is capable of transferring up to approximately 100 ml/min of oxygen and carbon dioxide. Initial data from the human trials suggest that gas transfer, although approaching these levels, varied widely in patients with respiratory failure. We studied the factors affecting gas exchange in 26 patients with severe acute respiratory failure who underwent intravenacaval support of gas exchange with IVOX. The patients underwent monitoring of IVOX gas transfer rates, hemodynamics, blood gases, and ventilation parameters at scheduled intervals following device insertion. All devices functioned following implantation. The mean value for O2 transfer was 64 +/- 21 SD ml/min (range 15-114 ml/min) and for CO2 transfer was 48 +/- 17 ml.min-1 (range 14-112 ml/min). CO2 transfer correlated positively with device surface area, cardiac output, and mixed venous Pco2 and negatively with duration of implantation. O2 transfer did not correlate with any patient factors probably due to error inherent in the measurement of this variable. Independent measurements of IVOX gas transfer by respiratory gas exchange in a subset of patients with normal values of mixed venous Pco2 were in good agreement with the routine measurements and indicated that the device provided up to 26% of gas exchange requirements in this subset. We conclude that IVOX transfers clinically useful amounts of oxygen and carbon dioxide in vivo. Factors that influence gas transfer include device surface area, PvCO2, cardiac output, and duration of implantation. Optimization of these factors (such as with permissive hypercapnea) could result in enhanced performance in vivo. PMID- 7864735 TI - Major findings from the clinical trials of the intravascular oxygenator. AB - Major clinically relevant findings have been extracted and summarized from the database developed from the international multicenter clinical trials of the intravascular oxygenator (IVOX) as a means for augmenting the deficient blood gas transfer of patients in advanced acute respiratory failure (ARF). Between February 1990 and May 1993, a total of 164 IVOX devices were utilized in 160 clinical trial patients who were hypoxemic and/or hypercarbic while receiving closed system positive pressure mechanical ventilator support at or exceeding generally accepted minimum safe levels of intensity. The average rates of oxygen and carbon dioxide transfer into and out of circulating venous blood by means of the IVOX device varied from 40-70 ml/min. Evidence of patient benefit during IVOX utilization includes improvement in blood gas partial pressures associated with decreased intensity of mechanical ventilation, improved hemodynamics in patients with mechanical ventilator depressed cardiovascular function, and decreased indices of lung dysfunction. Clinically recognized IVOX-related complications or adverse events were reported in 24.5% of the clinical trials patients. At necropsy examination of 68 clinical trials patients who died during or after IVOX utilization, forensic pathologists reported 4 cases in which IVOX utilization could have been a primary or contributing cause of death. Significant IVOX device mechanical and/or performance malfunction problems were recognized in 29 (17.7%) of the IVOX devices utilized in clinical trials. IVOX clinical trials data collected and analyzed to date indicate IVOX utilization has a favorable risk/benefit ratio in patients in severe, acute, potentially reversible ARF. PMID- 7864736 TI - Afterword: bottom-line status report: CAN current trends in membrane gas transfer technology lead to an implantable intrathoracic artificial lung? AB - For at least 170 years, attempts have been made to alleviate inadequate gas exchange of patients with respiratory failure. Major milestones in the struggle to assist failing natural lungs to achieve adequate blood gas exchange include utilization of oxygen inhalation therapy, mechanical ventilatory assistance, and development of both extracorporeal and intracorporeal mechanical blood gas exchangers. Current state-of-the-art technology related to mechanical membrane blood gas exchangers has produced highly efficient gas transfer membranes and designs capable of replacing all the gas transfer functions of the natural lungs by a mechanical oxygenator-CO2 remover that can fit into a unilateral thoracic cavity. The possibility thus exists of moving extracorporeal mechanical blood oxygenators into the body as an implantable intracorporeal artificial lung. Problems impeding the development of an implantable, intrathoracic artificial lung have been identified, and at least partially successful attempts to solve them have been reported. The conclusion drawn is that the appropriate answer to the question posed in the title of this communication is affirmative. Reasons for this conclusion include the persistent widespread major need for better relief from respiratory failure, the advanced state-of-the-art of mechanical blood gas exchanger technology, and the incompletely tapped ingenuity of the human mind. PMID- 7864737 TI - The optic neuritis treatment trial: three-year follow-up results. PMID- 7864738 TI - Laser therapy for retinopathy of prematurity. PMID- 7864739 TI - Laser therapy for retinopathy of prematurity. PMID- 7864740 TI - Genetic studies with animals. PMID- 7864741 TI - The use of a new laser lens holder for performing suture lysis in children. PMID- 7864742 TI - Magnetic resonance imaging findings in a patient with nuclear oculomotor palsy. PMID- 7864743 TI - Exercise band-induced hyphema. PMID- 7864744 TI - Bilateral macular holes in von Hippel-Lindau disease. PMID- 7864745 TI - Evaluating quality of care in the new health care environment. AB - Today's health care environment explicitly emphasizes quality monitoring and improvement systems. To better understand the new concepts of quality, the quality systems currently used and under development at the Doheny Eye Institute, Los Angeles, Calif, and The Wilmer Ophthalmological Institute, Baltimore, Md, were reviewed and the underlying principles and pertinent examples extracted. In the future, quality monitoring will require measurement of rates of conformance with indicators of each of the three components of quality of care, ie, structures, processes, and outcomes. As such, significant changes in the philosophy of quality monitoring and development of newer and more advanced measures and indicators will be needed to meet the challenges of quality review in the new health care environment. PMID- 7864746 TI - Effects of ocular surface area and blink rate on tear dynamics. AB - OBJECTIVE: To study the effects of exposed ocular surface area and blink rate on tear dynamics by the measurement of tear evaporation under a range of conditions. METHODS: Tear evaporation was measured in three gaze positions in 15 normal volunteers, and the ocular surface area was determined as a function of the width of the palpebral fissure. In 17 normal volunteers, the effect of blink rate on tear evaporation was assessed. RESULTS: The ocular surface area was 1.2 +/- 0.27, 2.2 +/- 0.39, and 3.0 +/- 0.33 cm2 with patients looking down, ahead, and up, respectively. The corresponding tear evaporation rates per eye were 7.0 +/- 3.5, 17.6 +/- 6.6, and 23.7 +/- 6.3 x 10(-7) g/s, respectively. The tear evaporation per square meter also increased proportionally with the ocular surface area. When the blink rate was changed from 10 to 60 per minute, the tear evaporation did not change in those individuals with evaporation rates more than 7.8 x 10(-7) g/s per square centimeter, whereas it did increase with the blink rate in those whose evaporation rates were lower. CONCLUSIONS: Ocular surface area and blink rate affect tear dynamics. Moderate palpebral fissure width and blink rate are necessary for the prevention of desiccation of the ocular surface. PMID- 7864747 TI - One-year results of the intrastromal corneal ring in nonfunctional human eyes. Intrastromal Corneal Ring Study Group. AB - OBJECTIVE: The intrastromal corneal ring (ICR), a new keratorefractive device designed to correct myopia, was evaluated for safety and efficacy as part of a phase I Food and Drug Administration clinical trial. PATIENTS AND METHODS: Ten patients, each with one nonfunctional eye, underwent surgical implantation of the ICR, which is a split ring composed of polymethyl methacrylate. The eyes were followed up during a 1-year period and were evaluated for wound healing, implant related inflammation, intraocular pressure, corneal thickness, endothelial cell count, and refractive effects. RESULTS: Wound healing was uncomplicated in all of the patients. No patient experienced implant-associated inflammation or extrusion. Intraocular pressure, corneal thickness, and endothelial cell counts were unaffected by the ICR. Non-sight-threatening intraoperative events included ring decentration and inadequate attachment of a vacuum-centering guide. The ICR reduced keratometrically determined spherical equivalence by an average of -2.5 +/- 1.1 diopters (mean +/- SD). Spherical equivalence, as determined by retinoscopy, was reduced by an average of -2.4 +/- 1.0 D. Results of corneoscopy and computerized videokeratography further confirmed this reduction of myopia. CONCLUSIONS: The ICR may be a safe and efficacious device that offers predictable results with few side effects, and it may be a feasible alternative to current keratore-fractive procedures. PMID- 7864748 TI - Magnetic resonance imaging in patients with low-tension glaucoma. AB - OBJECTIVE: To study diagnoses and anatomic findings found on magnetic resonance imaging in patients with low-tension glaucoma. PATIENTS: We included in this study magnetic resonance images of 20 consecutive patients with low-tension glaucoma. We individually matched each patient with low-tension glaucoma to a control with normal ocular findings who had magnetic resonance imaging for reasons unrelated to the visual pathway. DESIGN: We studied axial and coronal images of the orbit and optic nerve with digitizing software (Image-Pro Plus, Media Cybernetics, Silver Spring, Md). Statistical evaluation was with a Wilcoxon Signed Rank Test for anatomic findings and a McNemar Test for diagnosis. RESULTS: We found no difference between groups in the optic nerve diameter or length, the carotid artery area, or the distance from the optic nerve to the carotid artery (P > .05). Left optic nerve area was greater in the control patients than patients with low-tension glaucoma (P = .026). The prevalence of intracranial abnormalities, including meningioma, aneurysm, and arteriovenous abnormality, was similar between groups (P > .05). However, diffuse cerebral small-vessel ischemic changes were found more in patients with low-tension glaucoma (n = 8) than control patients (n = 1) (P = .0196). CONCLUSIONS: This study proposes a hypothesis that cerebral small-vessel ischemia is more common in patients with low-tension glaucoma and potentially reflects indirectly a vascular cause of the optic nerve head damage at least in a subgroup of patients. Importantly, further research still is required to provide direct evidence for a vascular cause involved in low-tension glaucoma. PMID- 7864749 TI - Cataract extraction in adults with retinopathy of prematurity. AB - OBJECTIVE: To review the results of lensectomies performed to remove visually significant cataracts in adults with regressed retinopathy of prematurity, with special reference to postoperative vision and retinal complications. METHODS: A chart review of consecutive cases of cataract extraction in eyes with visually significant lens opacities and regressed retinopathy of prematurity was conducted. RESULTS: Fourteen consecutive eyes with retinopathy of prematurity in 10 adult patients were identified as having undergone lensectomy to manage a visually significant cataract. These cataract extractions were performed between June 1970 and February 1993. There were eight women and two men aged 16 to 43 years at the time of lensectomy. A variety of lenticular opacities were noted, the most common of which was nuclear sclerosis. Additionally, the nuclei were frequently much harder than would be expected for the patient's age. Phacoemulsification with implantation of a posterior chamber intraocular lens was the most common technique for cataract extraction. Eight eyes experienced improvement in visual acuity. However, when preoperative visual acuity was less than 20/200, postoperative acuity of 20/60 or better was uncommon. Six eyes were being treated for glaucoma before lensectomy. Glaucoma control was facilitated after lensectomy in six eyes. No combined cataract extraction and filtering procedures were performed. One eye developed a rhegmatogenous retinal detachment 76 months after cataract extraction. The retina was successfully reattached, but the eye suffered a substantial decrease in visual acuity. CONCLUSION: Cataract extraction in adult patients with retinopathy of prematurity may improve visual acuity, facilitate examination and treatment of the posterior segment, and aid in the management of glaucoma. The risk of retinal complications in these patients does not appear to be excessive. PMID- 7864750 TI - Autosomal dominant macular dystrophy simulating North Carolina macular dystrophy. AB - OBJECTIVE: To characterize an autosomal dominant macular dystrophy with highly variable expression that does not fall clearly into a known disease entity. METHODS AND PATIENTS: Clinical, angiographic, and electrophysiologic data of five affected members in a family of Indian origin were evaluated. Molecular genetic analysis was undertaken to assess whether the gene responsible for the phenotype in this pedigree mapped to a region previously assigned to dominantly inherited macular dystrophies, including North Carolina macular dystrophy. RESULTS: The fundus appearance in the proband simulated stage 3 North Carolina macular dystrophy. Affected relatives had features in common with pattern dystrophy, fundus flavimaculatus with a dark choroid, and dominantly inherited drusen. Linkage to loci assigned to a number of retinal dystrophies principally affecting the posterior pole, including the North Carolina macular dystrophy locus, was excluded. CONCLUSION: The findings support the view that different genotypes are associated with similar phenotypes in autosomal dominant macular dystrophy. PMID- 7864751 TI - Chromosome 19q cone-rod retinal dystrophy. Ocular phenotype. AB - OBJECTIVE: To describe the phenotype in a family with dominantly inherited cone rod dystrophy with chromosome assignment to a 19q locus, and to correlate this with current classifications of this retinal dystrophy. DESIGN: A detailed clinical examination including Goldmann perimetry was undertaken in all family members. Six members under the age of 30 years underwent dark-adapted electroretinography, color contrast-sensitivity measurement, dark-adapted static perimetry, and dark adaptometry. PATIENTS: The study included 34 affected and 22 unaffected patients in four generations of a pedigree that manifested autosomal dominant cone-rod retinal dystrophy linked to a chromosome 19q locus by genetic linkage analysis. RESULTS: Loss of visual acuity occurred in the first decade of life, onset of night blindness occurred after 20 years of age, and little visual function remained after the age of 50 years. Central and, later, peripheral retinal fundus changes were associated with central scotoma, pseudoaltitudinal field defects, and finally global loss of function. Psychophysical and electrophysiologic testing before the age of 26 years showed more marked loss of cone than rod function. CONCLUSIONS: The phenotype associated with this mutation does not fit well into previous subtypes of cone-rod dystrophy. Further studies will be needed to correlate specific genetic mutations in this group of conditions with the various clinical phenotypes. PMID- 7864752 TI - Ocular cicatricial pemphigoid. A case report of monozygotic twins discordant for the disease. AB - OBJECTIVE: To identify the major histocompatibility complex markers and the autoantibody associated with ocular cicatricial pemphigoid (OCP) in a proband, her unaffected cotwin, and the children of the cotwin. Ocular cicatricial pemphigoid is a chronic autoimmune disorder that affects the conjunctiva and other squamous epithelium. It is associated with the major histocompatibility complex class II alleles that are presumed to provide enhanced susceptibility to the disease. We encountered a pair of monozygotic female twins, one of whom has OCP. In addition to totally identical physical appearances since birth, the two sisters have identical blood groups. METHODS: The following studies were performed on the patient, her unaffected cotwin sister, and her children: (1) polymorphism of major histocompatibility complex class II genes by DNA typing, (2) sequence analysis of DQ beta gene second and third exons, and (3) serologic evaluation for the presence of anti-basement membrane zone autoantibodies specific for OCP by Western immunoblot with the use of skin and conjunctiva lysates as substrates. RESULT: Both monozygotic twins had the same HLA haplotypes. The sequence analysis of the second and third exons of DQ beta genes revealed no significant differences between the proband and her unaffected cotwin. Autoantibodies specific to OCP were detected only in the patient's serum. The serum of the unaffected cotwin and the other relatives did not demonstrate the presence of the OCP autoantibody. CONCLUSION: This isolated family study does not support a single-gene theory for the development of OCP. It is most likely due to a multigene effect and associated with environmental factors. PMID- 7864753 TI - Stromal healing following explantation of an ICR (intrastromal corneal ring) from a nonfunctional human eye. AB - We examined the cornea of the nonfunctional left eye of a 46-year-old man, which was enucleated 8 months following explantation of an ICR (Intrastromal Corneal Ring). Corneal haze was confined to the midstroma, in the region of the tissue from which the ICR had been removed. Stromal tissue in this area was subtly compressed and irregular. Electron microscopy in conjunction with cuprolinic blue staining demonstrated an unremarkable proteoglycan population and several areas of slight collagen disruption at midstromal depth at the site of the previously implanted ICR. We conclude that disruptions of the corneal stroma that remain 8 months following explantation of an ICR are minimal. PMID- 7864754 TI - Ultrastructure of contusion cataract. AB - We investigated the histopathologic condition of four lenses with contusion rosette cataract by light and electron microscopy; periods between blunt trauma and cataract extraction varied from 4 months to 40 years. The initial morphologic changes appear to be the formation of intercellular vacuoles within the lens epithelium and the swelling of superficial cortical lens fibers. Signs of beginning fiber degeneration within the edematous zone include fragmentation of fiber cytoplasm into droplets and globules, formation of abnormal membrane arrangements, and enlargement of intercellular spaces. Late rosette opacities manifest as sharply demarcated layers of vacuolic degeneration in the deeper cortex. We suggest that in contusion cataract, a traumatically induced dysfunction of the lens epithelium leads to an edema of superficial cortical lens fibers that subsequently undergo degeneration and produce a localized and permanent lamellar zone of vacuolation. With time and with the formation of new clear lens cells, this layer becomes gradually compressed and displaced deeper into the cortex. PMID- 7864755 TI - Hypertension, perfusion pressure, and primary open-angle glaucoma. A population based assessment. AB - OBJECTIVE: To evaluate the association of vascular factors with primary open angle glaucoma (POAG). DESIGN: A population-based prevalence survey of ocular disease among black and white residents. SETTING: Communities of east Baltimore, Md. PARTICIPANTS: A stratified cluster sample of 5308 residents 40 years of age or older. MAIN OUTCOME MEASURES: Primary open-angle glaucoma as defined by demonstrable glaucomatous optic nerve damage based on visual fields and/or optic disc findings. Intraocular pressure level was not a criterion for diagnosis. RESULTS: Systolic and diastolic blood pressure showed modest, positive association with POAG. The effect of blood pressure on POAG was modified by age, with a stronger association among older subjects. Lower perfusion pressure (blood pressure-intraocular pressure) was strongly associated with an increased prevalence of POAG, with a sixfold excess for those in the lowest category of perfusion pressure. CONCLUSION: These results suggest that POAG is associated with an alteration in factors related to ocular blood flow and a breakdown of autoregulation. PMID- 7864756 TI - Effect of intravitreal administration of indomethacin on experimental subretinal neovascularization in the subhuman primate. AB - OBJECTIVE: To examine the effect of indomethacin, a cyclooxygenase (CO) inhibitor, on laser-induced subretinal neovascularization (SRN) in the monkey. The CO pathway of arachidonic acid metabolism plays an important role in angiogenesis, and the inhibition of CO is known to inhibit angiogenesis in the cornea and in certain tumors. MATERIALS AND METHODS: A cannula was implanted into the vitreous cavity of 11 eyes of six monkeys and connected to an osmotic minipump. Indomethacin (25 micrograms/d) was delivered into the vitreous through the cannula for 14 days (seven eyes). Vehicle alone was injected for 14 days as a control (four eyes). Argon laser photocoagulation was then performed (eight spots at the posterior pole in each eye) to induce SRN. Fundus photographs and fluorescein angiograms were taken periodically to document the evolution of SRN. Light and electron microscopic examination was performed on two eyes of each group 8 weeks after photocoagulation. RESULTS: Subretinal neovascularization developed from 2 to 4 weeks after photocoagulation. The incidence of SRN, indicated by fluorescein leakage, was significantly lower (P < .05) in the group treated with indomethacin (14.3%, eight of 56 lesions) than in the control group (37.5%, 12 of 32 lesions). After 8 weeks, no fluorescein leakage was found in either the control or indomethacin-treated groups. Scar formation was found on histologic examination in both groups. No histologic evidence of indomethacin toxicity was seen in the adjacent retina. CONCLUSIONS: Intravitreal administration of indomethacin inhibits the formation of laser-induced SRN in monkey eyes. This is consistent with the participation of the CO pathway in the process of SRN formation and suggests that this pathway could be a potential target in the treatment of SRN. PMID- 7864757 TI - Pericytes of newly formed vessels in experimental subretinal neovascularization. AB - OBJECTIVE: To examine the role of pericytes in the progression of subretinal neovascularization in a primate model. METHODS: Subretinal neovascularization was induced by intense laser photocoagulation in four monkey eyes. Single eyes were enucleated at 3, 7, 14, and 21 days after photocoagulation and were studied with light and electron microscopy. RESULTS: Three days after photocoagulation, newly formed vessels were observed in the choroid and subretinal space. Although most of these vessels had an immature appearance and consisted only of endothelial cells that formed narrow lumens, mitotic figures of pericytes were occasionally found near the endothelial cells. Seven days after photocoagulation, all of the newly formed vessels possessed pericytes. Fourteen days after photocoagulation, many vessels appeared to be mature. Many sites of pericyte-endothelial cell contact were observed. These contacts were composed of cytoplasmic interdigitation and membrane apposition. By 21 days after photocoagulation, the mature vessels had increased in number, and the endothelial cells had many fenestrations with diaphragms. The pericyte coverage of the endothelial cells was less at this stage than at 14 days after photocoagulation, and sites of pericyte endothelial cell contacts were observed only rarely. CONCLUSION: Pericytes are involved in maturation of the endothelial cells that form subretinal new vessels. PMID- 7864758 TI - The metabolic dependency of retinal adhesion in rabbit and primate. AB - OBJECTIVE: To determine the oxygen and glucose dependency of retinal adhesion in primate and rabbit. METHODS: Experiments were performed on Dutch rabbits and monkeys. Retinal adhesiveness was measured by peeling the retina from the retinal pigment epithelium in vitro, under different conditions of PO2 and glucose supply, and by observing the amount of adherent pigment. In vivo ischemia was produced by raising the intraocular pressure. RESULTS: Retinal adhesion failed quickly at low oxygen tensions, but a well-oxygenated solution preserved strong retinal adhesion in vitro for 15 to 20 minutes in rabbit tissue and up to 50 minutes in primate tissue. Ischemic adhesive failure was reversible on raising the PO2. Glucose levels did not affect adhesiveness. Ischemia in vivo for more than 1 minute caused rabbit retina to lose its adhesiveness. CONCLUSIONS: Retinal adhesion is continually and reversibly dependent on oxygenation, and probably on aerobic metabolism. Primate tissue is more resistant to metabolic adhesive failure than is rabbit tissue, but the metabolic requirements appear qualitatively similar. PMID- 7864759 TI - Mitomycin C suppresses aqueous human flow in cynomolgus monkeys. AB - OBJECTIVE: To determine whether mitomycin C suppresses aqueous humor formation in cynomolgus monkeys. METHODS: Three monkeys received subconjunctival injections (50 microL) in four quadrants bilaterally, one eye receiving mitomycin C (0.5 mg/mL) and the other receiving distilled water. Seven monkeys underwent 360 degrees conjunctival peritomy bilaterally and episcleral application of mitomycin C-soaked (0.5 mg/mL) cellulose sponges for 5 minutes in all four quadrants unilaterally. Aqueous humor flow was measured fluorophotometrically 1 and 3 days, and 1, 2, and 4 weeks after subconjunctival injection; and 3 days and 1, 2, 3, and 4 weeks after episcleral application. RESULTS: There was no change in aqueous flow in either eye and no difference between eyes following subconjunctival injection. Aqueous flow was reduced by 8% +/- 7% (mean +/- SEM), 20% +/- 3% (P < .01), 9% +/- 10%, and 0% +/- 4% compared with contralateral controls 1, 2, 3, and 4 weeks, respectively, after episcleral application of mitomycin C. CONCLUSIONS: Episcleral application of mitomycin C can produce at least a modest short-term reduction of aqueous humor flow in primates. Reduced aqueous flow might contribute to early postoperative hypotony following trabeculectomy with mitomycin C. PMID- 7864760 TI - Congenital absence of Descemet's membrane. PMID- 7864761 TI - Abnormal disc vessels after diabetic papillopathy. PMID- 7864762 TI - The human face of litigation. PMID- 7864763 TI - An approach to ear, nose and throat assessment. AB - An approach is described for assessing ear, nose and throat problems, which may be of assistance to general practitioners in diagnosing common ENT problems. Making an ENT diagnosis requires your well honed skills of history taking and examination. This is aided by a few examination tools. PMID- 7864764 TI - Tropical ear. AB - Tropical ear is a commonly used term for otitis externa, which is an inflammatory condition of the external auditory canal. It is the most commonly seen cause of otalgia. This article reviews the diagnosis, management and classification of otitis externa, a condition that has a number of causes. PMID- 7864765 TI - Chronic nasal blockage. AB - When examining the nose for chronic blockage, check the septum position, and evaluate the state of the turbinates both before and after spraying with decongestant. Then exclude any tumour in the nose before introducing medical therapy or seeking a surgical opinion. Patients often don't appreciate how blocked they are, so don't assume that if they are not complaining that they wouldn't be very grateful once an improvement in their nasal airway is achieved. PMID- 7864766 TI - 'Doctor, my voice seems husky'. AB - Disorders of voice are a common problem in general practice. An understanding of the complex mechanism of voice production enables us to appreciate how many systemic disorders can affect voice. This article details the pathophysiology of voice production and how to assess the patient with hoarseness. Contemporary management of vocal disorders is described with reference to some newer surgical and investigative techniques. PMID- 7864767 TI - Vertigo: assessment and management. AB - Elucidation of the cause of vertigo must consist of an adequate history to see if a clinical entity such as BPPV or Meniere's Disease can be recognised, and a general physical examination with emphasis on: The ear--discharge, perforation, fistula sign and hearing. Vestibular system--nystagmus and Romberg test with past pointing and positional testing. CNS--cranial nerves, cerebellar signs and gait. CVS--BP and bruits in neck and cardiac irregularities. Audiogram, ENG and CT or MRI. The specific treatment must be supplemented by sympathetic, symptomatic therapy and reassurance that the condition is not a mystery but clearly defined. The probable cause and lines of treatment available can be explained. PMID- 7864768 TI - Otolaryngology head and neck surgery. A review of malignancies. AB - Head and neck tumours present early because they cause symptoms early and are easily visible. These tumours rarely metastasise beyond the head and neck region. Because of these factors they are readily treatable and its effectiveness followed. Prognosis of the common cancers is excellent. PMID- 7864769 TI - An analysis of the FRACGP exam. AB - This paper reports briefly on an analysis of data from five consecutive FRACGP examinations. Using new measurement technology, this study sought to investigate the reliability and efficiency of the exam, which has long been regarded as a valid and comprehensive assessment of competence for general practice in Australia. Results indicate that the examination achieves acceptable overall reliability, although some segments contribute more to the reliability than others. Suggestions for changes to improve reliability are made. A decision on implementing these changes must take into consideration any consequent changes in validity. PMID- 7864770 TI - The management of asthma in general practice. Results from the Australian Morbidity and Treatment Survey, 1990-1991. AB - Asthma is the third most commonly managed problem in general practice in Australia. This paper provides an overview of its management in general practice. PMID- 7864771 TI - Treatment of herpes simplex and varicella zoster infections. AB - The introduction of antiviral agents such as acyclovir has had a remarkable impact on management of patients with viral infections. In this article the authors outline the management of herpes simplex and varicella zoster infections, giving specific guidelines for treatment with acyclovir. PMID- 7864772 TI - Training by helicopter. Extracts from a rural medical educator's notebook. AB - This paper reports the experience of one visiting clinical teacher on a teaching visit to a trainee rural doctor in the remote tropical north. Such teaching visits are interesting, may be adventurous and are always welcomed by trainees as they may have limited opportunities to discuss challenging clinical issues with other doctors. PMID- 7864773 TI - In sickness and in health. PMID- 7864774 TI - Pictorial essay. Systemic lupus erythematosus. PMID- 7864775 TI - November miscellany. PMID- 7864777 TI - Infectious disease case study. PMID- 7864776 TI - Timothy Murrell. The general practitioner as human ecologist. PMID- 7864778 TI - Emergency care: an overview. AB - Emergency care is a most important component in general practice. Practitioners are often judged by their ability to deliver appropriate life saving care sometimes in difficult circumstances. An ever present challenge is the maintenance of knowledge and skills necessary to deal effectively with emergencies. Table 3 lists the many emergencies that general practitioners have to consider to be prepared for and that includes regular updating in the basic skills of resuscitation. PMID- 7864779 TI - Travellers' aids. PMID- 7864780 TI - Alternative to abortion. PMID- 7864781 TI - Practice tip. Topical anaesthesia for children's lacerations. PMID- 7864782 TI - Social ills challenge the GP. PMID- 7864783 TI - House call at 20,000 feet. PMID- 7864784 TI - A hair transplant surgeon in Saudi Arabia. PMID- 7864785 TI - A volunteer in Zaire. AB - It is pretty easy to feel useful in a situation like this. The refugees are grateful for any help. Sometimes I miss the direct patient contact, but someone has to do the organising. To be honest--I enjoy the challenge. I wake up full of energy every morning, and when I go to bed I feel I have accomplished something. What I miss most is good food. We eat military combat rations every day. With only four different packs to choose from, it gets a bit boring. At times I miss Australia, my chosen home for the past 8 years, and hopefully for many more years to come. PMID- 7864786 TI - A doctor on duty in Antarctica. PMID- 7864787 TI - Antibiotics for common respiratory infections. AB - One of the most common reasons for prescribing antibiotics is an infection in the respiratory tract. There are a large number of antimicrobial agents available, some of long standing and others relatively new to the market. The rationale for the choice of agent, including emerging resistances, spectrum of activity, antibiotic pharmacokinetics, adverse reactions and cost, is discussed for the various sites of infection. PMID- 7864788 TI - Musculoskeletal medicine tip. Injection into acromioclavicular joint. PMID- 7864789 TI - Eyelid infection in a child. PMID- 7864790 TI - Practice tip. Marking out excision lines. PMID- 7864791 TI - Hairdressing a health hazard. PMID- 7864792 TI - The management of osteoarthritis in general practice. PMID- 7864794 TI - Analysis of water-soluble antioxidants by high-pressure liquid chromatography. AB - The measurement of endogenous substances that function as biological antioxidants is of importance because the values obtained might be an index of future health. We quantified three water-soluble antioxidants by high-pressure liquid chromatography with electrochemical detection (h.p.l.c.-e.c.). Current-voltage relationships made at various settings of the D2 porous graphite electrode help to identify ascorbic acid, glutathione and uric acid. The antioxidants are determined simultaneously and without need for derivatization. The method is seen to be useful for comparison of normal rat liver with liver that had undergone oxidative stress through ischaemia. Antioxidant levels in liver, kidney, pancreas and intestinal mucosa are presented and compared with literature values. Endogenous contents of oxidized forms of ascorbic acid and glutathione become apparent following exposure of tissue samples to a strong reductant such as 2 mercapthoethanol. PMID- 7864793 TI - Rapid and regulated degradation of ornithine decarboxylase. PMID- 7864795 TI - Evidence that the thyrotropin-releasing hormone receptor and its ligand are recycled dissociated from each other. AB - We have examined the trafficking of the thyrotropin-releasing hormone receptor (TRHR) and its ligand, after TRHR-TRH internalization in rat pituitary GH4C1 cells. After rapid ligand-induced receptor sequestration, the cell surface receptor pool was replenished. Replenishment was insensitive to inhibition of protein synthesis and was dependent on the duration of internalization; therefore, the replenished receptors were not newly synthesized but recycled. The total amount of recycled receptors decreased with increasing internalization time, resulting in only partial replenishment of the cell-surface receptor pool after prolonged incubation with ligand. Thus, in addition to a receptor recycling pathway, a non-cycling route exists for TRHR sorting; this route became dominant with increasing internalization periods. TRHR entry into these pathways was not determined by the affinity of the receptor-ligand interaction, because the extent of receptor recycling was similar after TRH- and methyl-TRH (MeTRH)-induced internalization. Unlike results with the TRHR, the TRH recycling pool was not depleted by the noncycling pathway. After multiple rounds of [3H]MeTRH internalization, the amount of cell-associated radioactivity increased with increasing internalization time due to accumulation of the ligand or its metabolites in a non-cycling pathway, but the absolute amount of recycled ligand remained constant after short or long internalization times. The difference in the proportion of TRHR and MeTRH that were diverted into a noncycling pathway indicated intracellular dissociation of the internalized TRHR-TRH complex. Dissociation of the internalized TRHR-TRH complex was dependent on the acidic pH in an intracellular compartment. Although extracellular acidic pH did not enhance cell-surface receptor-ligand (RL) dissociation, bafilomycin A1 inhibited both receptor and ligand recycling. We conclude that the TRHR-TRH system is unique among recycling receptors because, after RL sequestration, the TRHR-TRH complex becomes dissociated intracellularly via a bafilomycin A1-sensitive, acidic pH dependent mechanism, and both the unoccupied TRHR and TRH recycle disassociated from each other. PMID- 7864796 TI - Effect of synthetic peptides representing the hypervariable region of p21ras on Xenopus laevis oocyte maturation. AB - The carboxy-terminal hypervariable regions of p21ras proteins have been highly conserved throughout evolution but no function has been assigned to them yet. This region has been suggested as a possible candidate for receptor recognition. We have tested the possibility of this region being involved in p21ras biological function. Synthetic peptides corresponding to the hypervariable domains of p21N ras and p21K(B)-ras were microinjected into Xenopus oocytes to assess their effect on oocyte maturation. The K(B)-ras peptide inhibited insulin-dependent but not progesterone-dependent maturation, in contrast with the N-ras peptide which did not inhibit maturation significantly. A control peptide, with the same amino acid composition as the K(B)-ras peptide but with a scrambled sequence, and poly(D,L-lysine) were inactive. Pentalysine had partial activity which may be due to its mimicking the lysine-rich stretch of the K(B)-ras sequence. The data support the hypothesis that the K(B)-ras gene product specifically is involved in transducing the insulin and/or insulin-like growth factor 1 signal. PMID- 7864797 TI - The roles of multiple pathways in regulating bombesin-stimulated phospholipase D activity in Swiss 3T3 fibroblasts. AB - The regulation of bombesin-stimulated phospholipase D (PLD) activity in Swiss 3T3 fibroblasts was examined. Increasing protein-tyrosine phosphorylation by using pervanadate to inhibit tyrosine phosphatases was found to stimulate protein kinase C (PKC)-independent [3H]phosphatidylbutanol ([3H]PtdBut) accumulation within 5 min, which continued to increase up to 30 min. The stimulation of PLD activity in response to submaximal [bombesin] could be decreased by approx. 50% by the tyrosine kinase inhibitor genistein, whereas pretreatment with genistein and the PKC inhibitor Ro-31-8220 completely abolished the generation of [3H]PtdBut in response to a maximal concentration of bombesin. The addition of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) into permeabilized cells resulted in an increase in [3H]PtdBut, which was abolished by depletion of cellular ATP. The additional presence of 30 microM GTP[S] did not increase the stimulation of PLD activity by any [bombesin] tested, whereas it was synergistic with that stimulated in response to phorbol 12-myristate 13-acetate. These findings suggest that bombesin-stimulated PLD activity is indirectly regulated by G-proteins, possibly through a kinase intermediate. Furthermore, activation of protein tyrosine kinases is proposed to account for the PKC-independent arm of bombesin stimulated PLD activity. No evidence was obtained for a form of PLD directly regulated by tyrosine phosphorylation. PMID- 7864798 TI - Kinetic study in vitro of Escherichia coli promoter closure during transcription initiation. AB - The rate of closure of two Escherichia coli promoters borne by plasmid pBR322, following transcription initiation from the open complex, was probed in vitro by the protection of unpaired thymines in the open complex against oxidation by KMnO4. Run-off transcription kinetics were also studied under identical conditions. Closure of the open promoter appears to be by far the rate-limiting step of transcription initiation and elongation for the linearized beta-lactamase gene, and is strongly dependent on template topology for the RNAI gene. It is suggested that the corresponding signals are deposited 30 bases at least downstream of transcription initiation and that promoter closure, and its clearance by elongating RNA polymerase, may occur almost simultaneously. PMID- 7864799 TI - Identification of a novel form of the alpha 3 integrin subunit: covalent association with transferrin receptor. AB - The alpha 3 beta 1 integrin is a cell-surface receptor for laminin, entactin, collagen, fibronectin and epiligrin. On some prostatic-carcinoma cell lines that express the alpha 3 beta 1 heterodimer we have identified a novel form of the alpha 3 subunit. Whereas the prototypic alpha 3 subunit has a molecular mass of approximately 155 kDa, we have isolated a approximately 225 kDa protein (p225) which is recognized by monoclonal antibodies to the alpha 3 subunit. Protein sequence analysis revealed that p225 consists of two polypeptides, namely integrin alpha 3 heavy chain (approximately 130 kDa) disulphide-bonded to a monomer of the transferrin receptor (approximately 95 kDa) instead of the typical alpha 3 light chain (approximately 25 kDa). The p225 seems to be directly associated with beta 1 subunit, since it was immunoprecipitable with anti-(beta 1 subunit) antibodies. The association of transferrin receptor and integrin alpha 3 was apparently not the result of spurious disulphide-bond formation occurring during the protein purification, as iodoacetamide and GSH did not block the formation of the complex. The transferrin receptor is normally a homodimer that is involved in the internalization of iron-bound transferrin into cells and can be expressed at relatively high levels in the cell lines which we have studied. The p225 is not found on all cell types examined to date and therefore it may represent a unique complex between the integrin alpha 3 subunit and the transferrin receptor, a covalent association which may play a role in the adherence and/or proliferation of some types of tumour cells. PMID- 7864800 TI - Further characterization of the acid-soluble phosphoprotein (SDS/PAGE apparent molecular mass of 22 kDa) in rat fat-cells by peptide sequencing and immuno analysis: effects of insulin and isoprenaline. AB - 1. Earlier studies have shown that exposure of fat-cells to insulin results in the rapid increased phosphorylation of an acid-soluble protein which migrates as a doublet on SDS/PAGE with an apparent molecular mass of close to 22 kDa; agents such as isoprenaline, which increase cell concentrations of cyclic AMP, also increase phosphorylation, but to a lesser extent [Belsham, Brownsey, Hughes and Denton (1980) Diabetologia 18, 307-312; Diggle and Denton (1992) Biochem. J. 282, 729-736]. 2. The protein has been purified from rat epididymal adipose tissue, and the sequences of six tryptic peptides were determined. All six peptides are present in the deduced sequence of a protein of similar properties, designated PHAS-I by Hu, Pang, Kong, Velleca and Lawrence [(1994) Proc. Natl. Acad. Sci. U.S.A. 91, 3730-3734]. Hence the proteins are the same or extremely similar. 3. A rabbit anti-peptide antibody has been raised against one of the peptides (AGGDESQFEMD). The antibody was found to be highly specific for the phosphorylated and non-phosphorylated forms of the acid-soluble 22 kDa protein in Western blots and by immunoprecipitation. Studies with the antibody preparation have shown that both phosphorylated and non-phosphorylated forms of the protein appear to be exclusively located in the cytoplasm, and that exposure of cells to isoprenaline causes increased phosphorylation of the same acid-soluble 22 kDa protein as does insulin treatment. 4. Western blots carried out with the antibody preparation indicate that the protein is also present in other insulin-sensitive tissues, including liver, skeletal muscle, heart and brown adipose tissue. The protein was also detected in lung and spleen, but not brain and kidney. It is concluded that the protein may play an important role in some of the actions of insulin. PMID- 7864801 TI - Low NADPH oxidase activity in Epstein-Barr-virus-immortalized B-lymphocytes is due to a post-transcriptional block in expression of cytochrome b558. AB - The NADPH oxidase of phagocytes is known to be expressed in Epstein-Barr-virus transformed B-lymphocytes, albeit at levels only approx. 5% of those found in neutrophils. We have investigated the basis of this low level of expression and find that all four specific components of the NADPH oxidase are expressed in B lymphocytes, but only p47-phox protein attains levels equivalent with those found in neutrophils. This component was shown to phosphorylate and translocate to the membrane normally on activation. The other cytosolic component, p67-phox, did show a deficit, and by supplementing a B-cell cytosol extract with recombinant p67-phox, this was shown to account for the somewhat reduced activity of B-cell cytosol in a cell-free oxidase system. The cell-free analysis also clearly located the major deficiency in superoxide-generating capacity of B-lymphocytes to the membrane. Western blotting of membrane proteins revealed major reductions in the amount of cytochrome b558. Analysis of the levels of mRNA for both subunits of cytochrome b558, however, showed levels greater than expected. Significantly more mRNA for gp91-phox was present in B-cells than in undifferentiated HL60 cells, although it was not quite as abundant as in differentiated HL60 cells, which are capable of producing large amounts of superoxide. We conclude that the failure of B-lymphocytes to generate amounts of superoxide equivalent to those generated by neutrophils is primarily due to a post-transcriptionally determined block to the accumulation of cytochrome b558. PMID- 7864802 TI - Rapid purification and identification of calcyphosine, a Ca(2+)-binding protein phosphorylated by protein kinase A. AB - A method is presented for the rapid purification of dog thyroid calcyphosine, a protein previously identified as a major substrate for cyclic AMP-dependent protein kinase in dog thyroid slices stimulated by thyrotropin [Lecocq, Lamy and Dumont (1979) Eur. J. Biochem. 102, 147-152]. The protein was previously identified as a spot on two-dimensional gels and is now purified in its native form by a procedure involving three chromatographic steps. Homogeneous calcyphosine identified by SDS/PAGE, immunoblotting and peptide sequencing can be obtained within 7 h. As for calmodulin, Ca(2+)-dependent conformational changes can be shown by Ca(2+)-dependent hydrophobic interaction chromatography using phenyl-Sepharose. Unlike calmodulin, calcyphosine is a substrate for protein kinase A. PMID- 7864803 TI - Dissociation of the AT-specific bifunctional intercalator [N-MeCys3,N MeCys7]TANDEM from TpA sites in DNA. AB - We have examined the dissociation of [N-MeCys3,N-MeCys7]TANDEM, an AT-selective bifunctional intercalator, from TpA sites in mixed-sequence DNAs by a modification of the footprinting technique. Dissociation of complexes between the ligand and radiolabelled DNA fragments was initiated by adding a vast excess of unlabelled calf thymus DNA. Portions of this mixture were subjected to DNAse I footprinting at various times after adding the competitor DNA. Dissociation of the ligand from each site was seen by the time-dependent disappearance of the footprinting pattern. Within a natural DNA fragment (tyrT) the ligand dissociates from TTAT faster than from ATAT. We found that the stability of complexes with isolated TpA steps decreases in the order ATAT > TTAA > TATA. Dissociation from each of these sites is much faster than from longer regions of (AT)n. These results confirm the requirement for A and T base-pairs surrounding the TpA step and suggest that the interaction is strongest with regions of alternating AT, possibly as a result of its unusual structure. The ligand dissociates more slowly from the centre of (AT)n tracts than from the edges, suggesting that variations in dissociation rate arise from sequence-dependent variations in local DNA structure. PMID- 7864804 TI - Absolute and empirical determination of the enzymatic activity and kinetic investigation of the action of hyaluronidase on hyaluronan using viscosimetry. AB - We describe an investigation of the action of hyaluronidase on hyaluronan using viscosimetry. A new viscosimetric approach was developed for determining the activity of the enzyme in katal units. This approach requires knowledge of several parameters (e.g. Mark-Houwink constants) which were determined by combining viscosimetric measurement and gel-permeation chromatography analysis. Using all the necessary parameters we determined the kinetic parameters of the enzyme and found that 250 i.u. correspond to 1 nkat. An empirical viscometric was used to estimate the activity of the enzyme, and the Km was determined using the kinetic dilution method. The estimates produced by the absolute and empirical approaches were in good agreement. We demonstrate that the empirical estimation of the reaction rate is related to the rate of reaction expressed in absolute units and thus provides a good estimate of enzyme activity. Furthermore, we have found an empirical relationship which enables investigation of the kinetics of the enzyme in a simple and sensitive way by viscosimetry. PMID- 7864805 TI - Expression and alternative splicing of the cytochrome P-450 CYP2A7. AB - In order to investigate the relative levels of expression of human cytochrome P 450 (P-450) CYP2A genes and determine how this relates to polymorphism in coumarin hydroxylase activity, cDNA clones for members of the CYP2A gene family were isolated. These clones were CYP2A6, CYP2A7 and an alternatively spliced version of CYP2A7 (CYP2A7AS). The latter clone was missing exon 2, but contained a 10 bp segment of intron 1. Translation of CYP2A7AS resulted in an in-frame deletion of 51 amino acids. The expression of these cDNAs in COS-7 cells showed that both CYP2A6 and CYP2A7 generated a protein of molecular mass 49 kDa, whereas the protein product of CYP2A7AS was about 44 kDa. Only the CYP2A6 had coumarin hydroxylase activity. The relative level of CYP2A7 and CYP2A7AS mRNA was investigated by reverse transcription followed by PCR (RT-PCR) using human liver RNAs and an RNA sample from a human skin fibroblast cell line. In one of five liver RNAs studied, the aberrantly spliced CYP2A7 mRNA was 3-4-fold more abundant than the normal mRNA. The other samples contained very low levels of this mRNA species. Interestingly, CYP2A7AS mRNA was the major CYP2A7 mRNA detected in the fibroblast cell line. In this case only a protein band of 44 kDa was observed by Western-blot analysis. The relative of mRNA encoding CYP2A6 and CYP2A7 was established in seven human liver samples by RT-PCR and found to range between 1:0.5 and 1:3. These data strength the previous findings that alternative splicing is an important factor in determining the levels of many human P-450s and that this may be subject to tissue-specific effects. Whether in this case the protein product has some function remains to be determined. PMID- 7864806 TI - Phospholipase A2 from plasma of patients with septic shock is associated with high-density lipoproteins and C3 anaphylatoxin: some implications for its functional role. AB - Phospholipase A2 (PLA2) activity was purified 12,544-fold with a 13% yield from the plasma of patients diagnosed of septic shock by the sequential use of heparin agarose affinity chromatography, gel filtration, and reverse-phase f.p.l.c. Gel filtration chromatography of plasma omitting high-ionic-strength buffer revealed a molecular mass different from that of purified PLA2 and co-elution with apolipoprotein A-I peaks, which suggests its association with high-density lipoproteins (HDL). N-terminal analysis of the enzyme activity protein band, electroblotted from a SDS-acrylamide gel and with an assessed molecular mass of 19 kDa, showed an identical sequence to that of alpha-chain of human C3 complement component, suggesting the presence in this band of a complex formed by a complement C3-derived anaphylatoxin (C3a)-related fragment and the PLA2 linked side-by-side. Because the preparation of plasma enzyme showed lower activity than the enzyme obtained from fibroblasts transfected with the coding sequence of human group-II PLA2, and because the addition of C3-derived anaphylatoxins from human serum inhibited the activity of this recombinant PLA2, it was considered that C3a-related peptides behave as inhibitors of group-II PLA2. The enzyme showed optimal activity on [14C]oleate-labelled autoclaved E. coli, on synthetic phosphatidylethanolamine, and on [3H]arachidonate-labelled membranes of the monoblast cell line U937, but it did not show any activity on the release of [3H]arachidonate from pre-labelled human polymorphonuclear leukocytes (PMNs). In short, PLA2 from plasma of sepsis patients shows unique associations with other plasma proteins which may influence its functional properties. The association with C3-related peptides shows an inhibitory effect on the enzyme activity, whereas the association with HDL might influence its environment and/or its interaction with cells. The study of the catalytic properties shows a prominent effect on bacterial phospholipids, synthetic phosphatidylethanolamine, and membranes from U937 monoblasts, but not on synthetic phosphatidylcholine or on PMNs, even when these cells were maintained in culture to allow spontaneous apoptosis and became a good substrate for pancreatic type PLA2. PMID- 7864807 TI - Structure of heparan sulphate from human brain, with special regard to Alzheimer's disease. AB - Heparan sulphate (HS) was isolated after proteolytic digestion of cerebral cortex, obtained at autopsy, of patients with Alzheimer's disease (AD) and of control subjects. Deaminative cleavage in combination with selective radiolabelling procedures showed that the N-acetylated regions in the intact polysaccharides ranged from isolated residues to approximately 10 consecutive N acetylated disaccharide units, without any apparent difference between AD and control HS. The yield of disaccharide deamination products was slightly higher with AD than with control HS, suggesting a differential distribution of N sulphate groups. Separation of the disaccharides by anion-exchange h.p.l.c. yielded four mono-O-sulphated and one di-O-sulphated disaccharide; these components occurred in strikingly similar proportions in all cerebral HS preparations (except polysaccharide from neonatal brain) irrespective of the age of the individual and the histopathology of the cortex specimen. No significant difference was noted between HS obtained from control and from AD tissue. By contrast, the composition of HS isolated from brain differed significantly from that of HS preparations derived from other human organs. PMID- 7864808 TI - Mitomycin C binding to poly[d(G-m5C)]. AB - Poly[d(G-m5C)] was modified by reductively activated mitomycin C, an anti-tumour drug, under buffer conditions which are known to favour either the B or the Z conformations of DNA. C.d. and 31P-n.m.r. were used to characterize the poly[d(G m5C)]-mitomycin cross-linked complexes, as well as the effects on the equilibrium between the B and Z forms of the polynucleotide. Mitomycin C appears to inhibit the B-->Z transition, even in the presence of 3 mM MgCl2, while the Z-form of poly[d(G-m5C)] does not interact significantly with the drug under bifunctionally activating conditions; thus no reversion from the Z-form to the B-form of the polynucleotide can be observed under the salt conditions which are required for the Z-form to exist. PMID- 7864809 TI - The primary elastase inhibitor (elastasin) and trypsin inhibitor (contrapsin) in the goat are serpins related to human alpha 1-anti-chymotrypsin. AB - Two primary serine proteinase inhibitors in goat plasma have been isolated and characterized. The N-terminal sequence analysis of the purified proteins revealed that they are closely related to each other and are highly homologous to human alpha 1-anti-chymotrypsin rather than alpha 1-proteinase inhibitor. However, despite structural similarities the inhibitory specificity of the goat inhibitors differed from each other and from that of anti-chymotrypsin. In contrast with human anti-chymotrypsin, one of the goat inhibitors was shown to be a strong and specific inhibitor of trypsin (k(ass.) = 1.9 x 10(6) M-1.s-1), whereas the other was an efficient inhibitor of neutrophil elastase (k(ass.) = 1.5 x 10(6) M-1.S 1). Differences in the inhibitory specificity of each protein could readily be attributed to the amino acid sequence within the reactive site region. The trypsin inhibitor with an assumed arginine residue at the P1 position of the reactive-site peptide bond is referred to as 'contrapsin', and indicates that the occurrence of contrapsins is not restricted to rodents. In contrast, the inhibitory specificity, resistance to oxidative and proteolytic inactivation and the presence of a P1 leucine residue in the elastase inhibitor is unique among inhibitory serpins that have been characterized to date. Because this serpin is apparently the major elastase inhibitor in goat plasma, it is likely to be involved in the control of goat neutrophil elastase. Therefore, we suggest the name 'elastasin', and extend it to any other anti-chymotrypsin related serpins possessing neutrophil-elastase- inhibitory activity. PMID- 7864810 TI - Interaction of calponin with actin and its functional implications. AB - Titration of F-actin with calponin causes the formation of two types of complexes. One, at saturation, contains a lower ratio of calponin to actin (0.5:1) and is insoluble at physiological ionic strength. The another is soluble, with a higher ratio of calponin to actin (1:1). Electron microscopy revealed that the former complex consists of paracrystalline bundles of actin filaments, whereas the latter consists of separate filaments. Ca(2+)-calmodulin causes dissociation of bundles with simultaneous increase in the number of separate calponin-containing filaments. Further increase in the calmodulin concentration results in full release of calponin from actin filaments. In motility assays, calponin, when added together with ATP to actin filaments complexed with immobilized myosin, evoked a decrease in both the number and velocity of moving actin filaments. Addition of calponin to actin filaments before their binding to myosin resulted in a formation of actin filament bundles which were dissociated by ATP. PMID- 7864811 TI - Regulation of pyruvate carboxylase in 3T3-L1 cells. AB - When 3T3-L1 fibroblasts differentiate to adipocytes, the specific activity of pyruvate carboxylase (PC) increases about 25-fold in parallel with its intracellular protein concentration. The increase in PC protein concentration is accompanied by a 9-10-fold increase in the relative abundance of 4.2 kb PC mRNA measured by Northern-blot analysis using a cDNA probe encoding a segment of the PC gene of 3T3-L1 adipocytes. The effects of cyclic AMP (cAMP) alone and together with insulin on levels of cellular protein, PC activity, PC protein and on the relative abundance of PC mRNA were examined in mature 3T3-L1 adipocytes. Adipocytes exposed to cAMP for 24 h exhibited a 25% decrease in cellular protein and marked decreases in enzyme activity (88%) and PC mRNA abundance (98%) compared with untreated adipocyte controls. After 48 h of exposure to cAMP, PC activity and PC mRNA diminished to levels approaching their detection limits. When exposed to medium containing cAMP plus insulin, adipocyte enzyme activity and PC mRNA declined more slowly during the first 24 h exposure (about 20% decrease) but after 48 h fell to values comparable with those of adipocytes exposed to cAMP alone. Despite these decreases in enzyme activity, the PC protein content of adipocytes treated with cAMP alone or cAMP plus insulin are nearly identical with that of control adipocytes. The inactivation of PC in cAMP-treated adipocytes does not involve loss of the prosthetic group from the holoenzyme. Cross-linking experiments suggest that the spatial arrangement of protomers in inactive PC may differ from that in the active tetrameric enzyme. Data presented suggest that, in addition to inducing inactivation, cAMP may also regulate adipocyte PC by decreasing transcription of the PC gene and/or enhancing the rate of degradation of PC mRNA. PMID- 7864812 TI - Demonstration of specific insulin binding to cytosolic proteins in H35 hepatoma cells, rat liver and skeletal muscle. AB - We previously demonstrated that internalized insulin enters the cytoplasm before accumulating in nuclei of H35 rat hepatoma cells. This finding raises the possibility that insulin may interact with cytosolic proteins in addition to insulin-degrading enzyme (IDE). In the present study, cytosol from H35 hepatoma cells, rat liver or muscle was incubated with A14- or B26-125I-insulin at 4 degrees C for 5-120 min in the absence or presence of 25 micrograms/ml unlabelled insulin. 125I-insulin was cross-linked to cytosolic proteins by disuccinimidyl suberate and analysed by reducing or non-reducing SDS/PAGE and autoradiography. Our results demonstrate the presence of both tissue-specific and common cytosolic proteins which specifically bind insulin. In muscle cytosol, only two proteins of 27 and 110 kDa were specifically labelled with B26-125I-insulin. Seven major bands, of 27, 45, 55, 60, 76, 82 and 110 kDa, were labelled in rat liver cytosol. Detection of cytosolic insulin-binding proteins in H35-cell cytosol was dependent on cell-culture conditions. Labelling in cytosol from serum-deprived cells was decreased or absent compared with cytosol prepared from serum-fed or serum deprived cells treated with 100 ng/ml insulin for 1 h before preparation of the cytosol, in which six bands, of 32, 41, 45, 55, 82 and 110 kDa, were specifically labelled with B26-125I-insulin. This result suggests that the concentration or binding activity of some cytosolic insulin-binding proteins is rapidly regulated. Labelling of both rat liver and H35 cytosolic insulin-binding proteins was time dependent, and decreased or disappeared at 120 min in parallel with the degradation of labelled insulin. Fewer bands were specifically labelled with A14 125I-insulin than with B26-125I-insulin. The number of labelled bands observed under reducing and non-reducing conditions was not different in any of the cytosols. The 110 kDa band in all cytosols was identified as IDE by Western-blot analysis; the other proteins did not react with anti-IDE antibody and remain unidentified. 1,10-Phenanthroline (2 mM) increased IDE labelling, but decreased the labelling of 82 and 27 kDa bands. The marked difference in the number of cytosolic insulin-binding proteins in muscle and either H35 cells or liver suggests both that the labelling is specific and that these proteins serve a function and may be involved in some heretofore unknown mechanism of the signalling pathway by which insulin regulates cell growth or differentiation. PMID- 7864813 TI - Expression of an acidic isoform of calponin in rat brain: western blots on one- or two-dimensional gels and immunolocalization in cultured cells. AB - Calponin, an actin- and Ca(2+)-calmodulin-binding protein characterized as an inhibitory factor of the smooth-muscle actomyosin activity, has also been shown to be present in some non-muscle cells. However, there is a controversy as to whether calponin is present or not in brain. Several laboratories indicate that this protein is absent in chicken or bovine brains, while Applegate et al. [Applegate, Feng, Green and Taubman (1994) J. Biol. Chem. 269, 10683-10690] have recently reported the identification of an mRNA specific for a 36 kDa non-muscle calponin analogue in homogenates of rat brains. For the first time we demonstrate, by Western blots and in situ immunofluorescence localization using monoclonal as well as affinity-purified polyclonal antibody to gizzard calponin, that a 36-37 kDa and a 35-36 kDa calponin-like proteins are expressed respectively in pig and rat brains and in rat cerebellar cultured cells. The acidic pI (5.2-5.4) of the rat brain protein revealed by isoelectric focusing is in good agreement with that of the protein coded for by the calponin isoform mRNA described by Applegate et al. and is different from that of the protein from chicken gizzard (pI 9.9). Brain calponin-like protein is different from two other Ca(2+)-calmodulin-binding proteins previously identified in brain, namely caldesmon and adducin, and from tropomyosin. PMID- 7864814 TI - Tissue- and cell-specific expression of mouse xanthine oxidoreductase gene in vivo: regulation by bacterial lipopolysaccharide. AB - The expression of the xanthine oxidoreductase gene was studied in various mouse organs and tissues, under basal conditions and on treatment with bacterial lipopolysaccharide. Levels of xanthine oxidoreductase protein and mRNA were compared in order to understand the molecular mechanisms regulating the expression of this enzyme system. The highest amounts of xanthine oxidoreductase and the respective mRNA are observed in the duodenum and jejunum, where the protein is present in an unusual form because of a specific proteolytic cleavage of the primary translation product present in all locations. Under basal conditions, multiple tissue-specific mechanisms of xanthine oxidoreductase regulation are evident. Lipopolysaccharide increases enzyme activity in some, but not all tissues, mainly via modulation of the respective transcript, although translational and post-translational mechanisms are also active. In situ hybridization studies on tissue sections obtained from mice under control conditions or with lipopolysaccharide treatment demonstrate that xanthine oxidoreductase is present in hepatocytes, predominantly in the proximal tubules of the kidney, epithelial layer of the gastrointestinal mucosa, the alveolar compartment of the lung, the pulpar region of the spleen and the vascular component of the heart. PMID- 7864815 TI - Characterization of the invertase from Pichia anomala. AB - Synthesis of invertase (EC 3.2.1.26) in Pichia anomala is controlled by the carbon source in the culture medium. The enzyme was purified to homogeneity from P. anomala cells fully derepressed for invertase synthesis and shown to be a multimeric glycoprotein composed of identical subunits with an apparent molecular mass of 86.5 kDa. The carbohydrate moiety accounts for approx. 30% of the total mass of the molecule and consists of manno-oligosaccharides N-linked to the polypeptide. Most of the characteristics of the enzyme analysed in this study were similar to those previously reported for other yeast invertases, with the remarkable exception of its thermal sensitivity which appears after 15 min incubation at temperatures above 32 degrees C. PMID- 7864816 TI - Radiation-inactivation analysis of the Na+/bile acid co-transport system from rabbit ileum. AB - The functional-unit molecular size of the Na+/bile acid cotransport system and the apparent target size of the bile-acid-binding proteins in brush-border membrane vesicles from rabbit ileum were determined by radiation inactivation with high-energy electrons. The size of the functional transporting unit for Na(+)-dependent taurocholate uptake was determined to 451 +/- 35 kDa, whereas an apparent molecular mass of 434 +/- 39 kDa was measured for the Na(+)-dependent D glucose transport system. Proteins of 93 kDa and 14 kDa were identified as putative protein components of the ileal Na+/bile acid cotransporter in the rabbit ileum, whereas a protein of 87 kDa may be involved in passive intestinal bile acid uptake. Photoaffinity labelling with 3- and 7-azi-derivatives of taurocholate revealed a target size of 229 +/- 10 kDa for the 93 kDa protein, and 132 +/- 23 kDa for the 14 kDa protein. These findings indicate that the ileal Na+/bile acid co-transport system is in its functional state a protein complex composed of several subunits. The functional molecular sizes for Na(+)-dependent transport activity and the bile-acid-binding proteins suggest that the Na+/bile acid co-transporter from rabbit ileum is a homotetramer (AB)4 composed of four AB subunits, where A represents the integral 93 kDa and B the peripheral 14 kDa brush-border membrane protein. PMID- 7864817 TI - Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. AB - Cyclooxygenase (Cox) is a key enzyme in the biosynthesis of prostaglandins and, as such, is the target of non-steroidal anti-inflammatory drugs (NSAIDs). Two isoforms exist, being expressed constitutively (Cox-1), or inducibly in response to inflammatory mediators (Cox-2). Currently available NSAIDs inhibit both isoforms somewhat equipotently but selective Cox-2 inhibition may eliminate unwanted side effects. We have characterized the kinetic mechanisms of the interactions of purified recombinant human cyclooxygenase-1 and -2 (hCox-1, hCox 2) with the selective Cox-2 inhibitor N-(2-cyclohexyloxy-4 nitrophenyl)methanesulphonamide (NS-398) and some classical non-selective NSAIDs. NS-398, flurbiprofen, meclofenamic acid and indomethacin are time-dependent, irreversible inhibitors of hCox-2. The inhibition is consistent with a two-step process, involving an initial rapid equilibrium binding of enzyme and inhibitor, characterized by Ki, followed by the slow formation of a tightly bound enzyme inhibitor complex, characterized by a first-order rate constant kon. NS-398 is a time-independent inhibitor of hCox-1, consistent with the formation of a reversible enzyme-inhibitor complex. Flurbiprofen, meclofenamic acid and indomethacin are also time-dependent inhibitors of hCox-1 and hence show little selectivity for one isoform over the other. Flufenamic acid is time independent towards both isoforms and is also non-selective. The high degree of selectivity of NS-398 towards Cox-2 results therefore from the difference in the nature of the time-dependency of inhibition of the two isoforms. PMID- 7864818 TI - m-Acetylanilido-GTP, a novel photoaffinity label for GTP-binding proteins: synthesis and application. AB - A novel photoaffinity label, m-acetylanilido-GTP (m-AcAGTP), was synthesized and used to identify GTP-binding proteins (G-proteins). This GTP analogue is easily prepared and can be used for photoaffinity labelling of G-proteins without chromatographic purification. In the presence of the beta-adrenergic agonist isoprenaline, it activates turkey erythrocyte adenylate cyclase. This activation persists even when the beta-adrenergic receptor is subsequently blocked by antagonist, indicating that the GTP analogue is resistant to hydrolysis. The apparent Ka for activation of turkey erythrocyte adenylate cyclase by m-AcAGTP was found to be 0.21 microM, a value similar to that for guanosine 5'-[beta,gamma imido]triphosphate. m-AcAGTP also effectively inhibited the light-dependent GTPase of Musca fly eye membranes. Photoaffinity labelling of fly eye membranes with [alpha-32P]m-AcAGTP, followed by immunoprecipitation of G-protein Gq, identified a labelled protein band with the mobility of a 41.5 kDa protein on SDS/PAGE. Labelling of this protein was enhanced 9-fold in blue over red illuminated membranes, containing metarhodopsin and rhodopsin respectively. Labelling of alpha-subunits of heterotrimeric G-proteins was also demonstrated in turkey erythrocyte membranes. The ease of preparation of m-AcAGTP and the chemical properties of the photoreactive acetophenone make this affinity label an important new tool in studies of cellular phenomena mediated by guanine nucleotide-binding proteins. PMID- 7864819 TI - Enzymatic radiolabelling to a high specific activity of legume lipo oligosaccharidic nodulation factors from Rhizobium meliloti. AB - In this paper we describe the two-step coupled 35S-radiolabelling of the lipo oligosaccharidic nodulation (Nod) factors of the bacterium Rhizobium meliloti to a specific radioactivity of 800 Ci/mmol. These radiolabelled Nod factors bind to a particulate fraction from roots of the bacterium's symbiotic host, Medicago truncatula, with an equilibrium dissociation constant (KD) of 117 nM, similar to that observed with a synthetic tritiated ligand. The first step of the 35S labelling involves the synthesis of 3'-phosphoadenosine 5'-phospho[35S]sulphate ([35S]PAPS) from ATP and [35S]sulphate using yeast enzymes. The second step exploits the sulphotransferase activity of the R. meliloti NodH protein, which has been expressed in Escherichia coli, to transfer the labelled sulphate group from PAPS to non-sulphated Nod factors. This enzyme was found to be active in E. coli cultured at 18 degrees C but not 37 degrees C. NodH could also transfer the sulphate group from PAPS to a model substrate, tetra-N-acetyl chitotetraose, with apparent Km values of 56 and 70 microM respectively, and exhibited an apparent Km value for non-sulphated Nod factors of 28 microM. Coupling the two steps of the radiolabelling resulted in an efficiency of 35S incorporation from inorganic sulphate to the Nod factors of approximately 10%. These labelled factors will be a valuable tool in the search for high-affinity receptors for the lipo oligosaccharidic nodulation factors. PMID- 7864820 TI - Primary structures of seven metallothioneins from rabbit tissue. AB - Metallothionein from tissues of rabbits exposed to cadmium chloride was separated into seven distinct isoforms by reverse-phase liquid chromatography and their complete amino acid sequences were determined. Five of the seven isometallothioneins showed structural features so far not identified in other mammalian metallothioneins. Thus, two isoproteins contain a polypeptide with a chain length of 62 rather than 61 amino acid residues. Two isoforms are characterized by an additional positive charge and one by the presence of an isopeptide bond between aspartic acid and serine in the N-terminal half of the protein. The isoproteins characterized were identified from different sources: rabbit liver and kidney and a rabbit kidney cell-line (RK-13). In all three, the structural characteristics of the individual isoforms are retained, indicating that in the different tissues the same mechanisms control the synthesis and the stability of the different cadmium-induced isoMTs. PMID- 7864821 TI - The proteolytic processing site of the precursor of lysyl oxidase. AB - The precise cleavage site of the N-terminal propeptide region of the precursor of lysyl oxidase has not yet been established, due to N-terminal blocking of the mature protein. Using a combination of peptide fragmentation, amino acid sequencing, time-of-flight m.s. and partial chemical unblocking procedures, it is shown that the mature form of lysyl oxidase begins at residue Asp-169 of the precursor protein (numbered according to the human sequence). The cleavage site is 28 residues to the C-terminal side of the site previously suggested on the basis of apparant molecular mass by SDS/PAGE, with the consequence that the two putative, N-linked glycosylation sites and the position of the Arg/Gln sequence polymorphism are now all in the precursor region. PMID- 7864822 TI - Branched-chain-amino-acid-preferring peptidase activity of the lobster multicatalytic proteinase (proteasome) and the degradation of myofibrillar proteins. AB - The multicatalytic proteinase (MCP or proteasome) is a large proteolytic complex that contains at least five catalytic components: the trypsin-like, chymotrypsin like, peptidylglutamyl-peptide hydrolase (PGPH), branched-chain-amino-acid preferring (BrAAP) and small-neutral-amino-acid-preferring activities. We have shown that brief heating of the lobster muscle proteasome activates a proteolytic activity that degrades casein and myofibrillar proteins and is distinct from the trypsin-like, chymotrypsin-like and PGPH components. Here we identify the BrAAP activity as a catalytic component involved in the initial degradation of myofibrillar proteins in vitro. This conclusion is based on the following. (1) The BrAAP component was activated by heat-treatment, whereas the other four peptidase activities were not. (2) The BrAAP and proteolytic activities showed similar sensitivities to cations and protease inhibitors: both were inhibited by 3,4-dichloroisocoumarin, chymostatin, N-ethylmaleimide and Mg2+, but were not affected by leupeptin, phenylmethanesulphonyl fluoride or Li+. (3) The BrAAP activity was inhibited most strongly by casein substrates and troponin; conversely, the troponin-degrading activity was inhibited by the BrAAP substrate. Another significant finding was that incubation of the heat-activated MCP in the presence of chymostatin resulted in the limited cleavage of troponin-T2 (45 kDa) to two fragments of 41 and 42 kDa; this cleavage was completely suppressed by leupeptin. These results suggest that under certain conditions the trypsin-like component can cleave endogenous protein. PMID- 7864823 TI - Multiple steroid-binding orientations: alteration of regiospecificity of dehydroepiandrosterone 2- and 7-hydroxylase activities of cytochrome P-450 2a-5 by mutation of residue 209. AB - The mutation of Ala-117 to Val conferred dehydroepiandrosterone (DHEA) hydroxylase activity on cytochrome P-450 2a-4, with the production of both 2 alpha- and 7 alpha-hydroxyDHEA at similar rates. P-450 2a-5 which has Val at position 117, acquired high DHEA hydroxylase activity by mutation of Phe-209. Mutant F209L of P-450 2a-5 exhibited strong regiospecificity at the 2-position of the DHEA molecule with the production of 2 alpha-hydroxy DHEA as the major metabolite. On the other hand, mutant F209V of P-450 2a-5 showed the 7-position to be the major hydroxylation site, 7 beta-hydroxyDHEA and 7 alpha-OHDHEA being produced. Therefore the regiospecificity of DHEA hydroxylase activity of P-450 2a 5 is altered between the 2- and 7-position depending on the amino acid at position 209. Modelling of the DHEA molecule in the pocket of bacterial P-450cam showed that the steroid can be accommodated in at least two orientations for which the 2- or 7- position is near the sixth axial position of the haem. Moreover, these two orientations, which are of similar energy, can be interconverted by a 180 degrees rotation of the steroid molecule around its long axis. These results support the hypothesis that the steroid molecule in the pocket is in dynamic equilibrium with multiple binding orientations and that the equilibrium is apparently determined by a few critical residues including those at positions 117 and 209. PMID- 7864824 TI - Purification of a phosphatidic-acid-hydrolysing phospholipase A2 from rat brain. AB - A phosphatidic-acid-hydrolysing phospholipase A2 was purified from rat brain and characterized. This phospholipase A2 was purified by sequential cation, hydrophobic, heparin and gel-filtration chromatography. The purified protein had a mass of approximately 58 kDa as assayed by SDS/PAGE, had a pH optimum of 6.0, and was Ca(2+)-independent. This enzyme was apparently phosphatidic-acid selective and had little measurable catalytic activity when phosphatidylcholine, phosphatidylethanolamine or diacylglycerol was used as substrate. On the basis of its physical and catalytic properties, we conclude that this phospholipase A2 is unique from those previously purified, and we speculate that it may be important for the production of the bioactive lipid lysophosphatidic acid. PMID- 7864825 TI - Further evidence that the human MUC2 gene transcripts in the intestine and trachea are identical. PMID- 7864826 TI - Reversal of the Ca2+ pump of blood platelets. AB - In this study, the endoplasmic Ca2+ transport ATPase of blood platelets was compared with the Ca2+ ATPase of sarcoplasmic reticulum skeletal muscle. Similar to the muscle enzyme, the Ca2+ ATPase from platelets was found to catalyse an ATP<-->P(i) exchange both in the presence and in the absence of a transmembrane Ca2+ gradient. When platelet vesicles are loaded with Ca2+ and diluted in medium containing ADP, P(i) and EGTA, the ATPase catalyses Ca2+ efflux coupled to synthesis of ATP. The stoichiometry between Ca2+ ion released and ATP synthesized by platelet Ca2+ ATPase is 1, while that of skeletal muscle is 2. Thapsigargin, a specific inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+ ATPases, inhibited both the Ca(2+)-dependent ATPase activity and the reversal of the platelet Ca2+ pump. The possibility is discussed that the differences observed between the two transport systems is related to the distinct amino acid sequences of the enzymes. PMID- 7864827 TI - The structural origins of the unusual specificities observed in the isolation of chymopapain M and actinidin by covalent chromatography and the lack of inhibition of chymopapain M by cystatin. AB - 1. The selectivity observed when the potentially general technique for the isolation of fully active forms of cysteine proteinases, covalent chromatography by thiol-disulphide interchange, is applied to chymopapain M and to actinidin was investigated by a combination of experimentation and computer modelling. Neither of these enzymes is able to react with the original Sepharose-GSH-2-dipyridyl disulphide gel, but fully active forms of both enzymes are obtained by using Sepharose-2-hydroxypropyl-2'-dipyridyl disulphide gel, which is both electrically neutral and sterically less demanding than the GSH gel. Electrostatic potential calculations, minimization and molecular-dynamics simulations provide explanations for the unusual, but different, specificities exhibited by actinidin and chymopapain M in the interactions of their active centres with ligands. 2. The unique behaviour of chymopapain M in exerting an almost absolute specificity for substrates with glycine at the P1 position and in resisting inhibition by cystatin was examined by the computer-modelling techniques. A new, modelled, structure of the complete chicken egg-white cystatin molecule based on the crystal structure of a short form of cystatin was deduced as a necessary prerequisite. The results suggest that electrostatic repulsion prevents reaction of actinidin with the GSH gel, whereas a steric 'cap' resulting from a unique arginine-65-glutamic acid-23 interaction in chymopapain M prevents reaction of the gel with this enzyme and accounts for the lack of its inhibition by cystatin and its specificity in catalysis. 3. Use of chymopapain M as a structural variant of papain demonstrates the validity of the predictions of Lowe and Yuthavong [Biochem. J. (1971) 124, 107-115] relating to the structural requirements and binding characteristics of the S1 subsite of papain. PMID- 7864828 TI - Analysis of c-fos expression in the butyrate-induced F-98 glioma cell differentiation. AB - The functional induction of c-fos in the sodium butyrate-induced differentiation of F-98 glioma cells was studied. Fos protein level was increased by butyrate. In contrast, c-Jun protein was constitutively expressed and was not affected by butyrate. Gel-retardation assay indicates Fos as a component of the complex formed between the consensus oligonucleotide of the TPA (PMA, phorbol 12 myristate 13-acetate) response element (TRE) and nuclear extract prepared from butyrate-treated cells. Transfection studies showed that butyrate increased transcription from a multimeric TRE-driven reporter construct, and the effect was mimicked by transfecting cells with fos-expression plasmid. Furthermore, under conditions of c-fos over-expression, transactivation by butyrate was essentially abolished. These data suggest that Fos induction had a functional role in gene activation. Characterization of stable c-fos transfectants demonstrated that these cells displayed alterations in morphology, showed serum-dependent growth, had slower growth rates and grew to lower saturation densities than did untransfected F-98 cells or transfected cells that did not express c-fos. Immunofluorescent staining indicated that fos transfectants also had elevated glial fibrillary acidic protein ('GFAP') expression. Transfection of the c-fos promoter-chloramphenicol acetyltransferase fusion gene into F-98 cells revealed that activation of c-fos by butyrate was exerted at the promoter level, and sequences located within nucleotides -757 to -402 of the c-fos promoter were responsible for butyrate induction. Our data indicate that transcriptional activation of c-fos through its promoter by butyrate resulted in increased Fos protein expression. Transfection studies show that both c-fos and butyrate activate TRE-containing genes, and fos may be a downstream mediator of butyrate. Furthermore, expression of c-fos plays a major role in modulating the growth properties of F-98 cells. PMID- 7864829 TI - Sheep pancreatic microsomes as an alternative to the dog source for studying protein translocation. AB - A procedure is described for the preparation of rough membrane vesicles of endoplasmic-reticular origin from the pancreas of sheep. These isolated membranes translocate, process and glycosylate in vitro-translated heterologous proteins in a manner comparable with that exhibited by dog pancreatic microsomes. PMID- 7864830 TI - Determinants of the unusual cleavage specificity of lysyl-bradykinin-releasing kallikreins. AB - Kinetic data for the hydrolysis by human tissue kallikrein of fluorogenic peptides with o-aminobenzoyl-Phe-Arg (Abz-FR) as the acyl group and different leaving groups demonstrate that interactions with the S'1, S'2 and S'3 subsites are important for cleavage efficiency. In addition, studies on the hydrolysis of fluorogenic peptides with the human kininogen sequence spanning the scissile Met Lys bond [Abz-M-I-S-L-M-K-R-P-N-(2,4-dinitrophenyl)ethylenediamine] and analogues with different residues at positions P'1, P'2 and P'3 showed that (a) the presence of a proline residue at P'3 and the interactions with the tissue kallikrein-binding sites S2 to S'2 are determinants of Met-Lys bond cleavage and (b) residues P3, P4 and/or P5 arc important for cleavage efficiency. The substitution of phenylalanine for methionine or arginine in substrates with scissile Met-Lys or Arg-Xaa bonds demonstrated that lysyl-bradykinin-releasing tissue kallikreins also have a primary specificity for phenylalanine. The replacement of arginine by phenylalanine in (D)P-F-R-p-nitroanilide (pNA) produced an efficient and specific chromogenic substrate, (D)P-F-F-pNA, for the lysyl-bradykinin-releasing tissue kallikreins as it is resistant to plasma kallikrein and other arginine hydrolases. PMID- 7864831 TI - Immunoprecipitation of opioid receptor-Go-protein complexes using specific GTP binding-protein antisera. AB - Solubilization of opioid receptors from rat cortical membranes that retained high affinity guanine nucleotide-sensitive agonist binding was achieved using 10 mM CHAPS. We report the nature of the interactions of mu and delta opioid receptors with the guanine nucleotide-binding protein G(o) by immunoprecipitation of CHAPS extracts with selective G(o)alpha-subunit protein antisera. Antiserum IM1 raised against amino acids 22-35 of G(o)alpha selectively co-immunoprecipitated G(o)alpha-mu and G(o)alpha-delta opioid receptor complexes detected in the immunoprecipitates by specific [3H][D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin and [3H][D-Ser2,Leu5,Thr6]enkephalin binding respectively. By contrast, antisera directed against the C-terminal decapeptide (OC2) and the N-terminal hexadecapeptide (ON1) of isoforms of G(o)alpha were unable to immunoprecipitate solubilized opioid receptor-G(o) complexes, although both were able to immunoprecipitate solubilized G(o)alpha and have been shown to reduce the affinity of [D-Ala2,D-Leu5]enkephalin for opioid receptors in rat cortical membranes [Georgoussi, Carr and Milligan (1993) Mol. Pharmacol. 44, 62-69]. These findings demonstrate that CHAPS-solubilized mu and delta opioid receptors from rat cortical membranes form stable complexes with one or more variants of G(o). PMID- 7864833 TI - A novel exocytoplasmic endonuclease from Streptomyces antibioticus. AB - A new exocytoplasmic, nutritionally controlled endodeoxyribonuclease (EC 3.1.21. ) was purified to homogeneity from Streptomyces antibioticus. The enzyme showed an apparent molecular mass of 29 kDa (being active in the monomeric form) and a pI of approximately 7.8. The nuclease hydrolysed endonucleolytically double stranded circular and linear DNA. The enzyme makes nicks in one strand of the DNA in G-rich regions, leaving either 5' or 3' short, single-stranded overhangs with 3'-hydroxy and 5'-phosphate termini. Breaks in the DNA occur when two nicks in opposite strands are close together. The enzyme had an optimum pH of 7.5 and an absolute requirement for bivalent cations and > or = 100 mM NaCl in the reaction buffer. Activity was greatly diminished in the presence of phosphate, Hg2+ or iodoacetate and was stimulated by dimethyl sulphoxide. Single-stranded DNA was a much poorer substrate than double-stranded DNA. The nuclease hydrolyses sequences of three or preferably more (dG).(dC) tracts in the DNA. The initial specificity shifts to other sequences (including sequences shorter than those initially hydrolysed) during the course of the reaction, giving the changing pattern of bands observed in agarose gels. 5-Methylcytosine-hemimethylated DNA is not hydrolysed by the nuclease. The properties of this novel enzyme suggest a relationship with class II restriction endonucleases and also with some eukaryotic nucleases. PMID- 7864832 TI - Interaction of non-conjugated olefinic substrate analogues with dopamine beta monooxygenase: catalysis and mechanism-based inhibition. AB - The reaction of dopamine beta-monooxygenase (DBM; EC 1.14.17.1) with the prototypical non-conjugated olefinic substrate, 2-(1-cyclohexenyl)ethylamine (CyHEA) [see Sirimanne and May (1988) J. Am. Chem. Soc. 110, 7560-7561], was characterized. CyHEA undergoes facile DBM-catalysed allylic hydroxylation to form (R)-2-amino-1-(1-cyclohexenyl)ethanol (CyHEA-OH) without detectable epoxidation or allylic hydroxylation to form (R)-2-amino-1-(1-cyclohexenyl)ethanol (CyHEA-OH) without detectable epoxidation or allylic rearrangement, and with stereochemistry consistent with that of DBM-catalysed benzylic hydroxylation and sulphoxidation. The kcat. of 90 s-1 for CyHEA oxygenation is about 75% of the kcat. for tyramine, the substrate commonly used in assays of DBM activity. DBM-catalysed oxygenation of CyHEA also results in mechanism-based inactivation of DBM, with the inactivation reaction yielding kinact. = 0.3 min-1 at pH 5.0 and 37 degrees C, and a partition ratio of 16,000. Although both CyHEA turnover and inactivation exhibit normal kinetics, CyHEA processing also results in gradual depletion of copper from DBM; however, mechanism-based irreversible DBM inactivation occurs independent of this copper depletion when sufficient copper is present in the assay solution. A likely mechanism for turnover-dependent DBM inactivation by CyHEA involves initial abstraction of an allylic hydrogen to form a resonance stabilized allylic radical, which can then either partition to product or undergo attack by an active-site residue. Acyclic, non-conjugated olefinic analogues exhibit diminished substrate activity toward DBM. Thus, kcat. for oxygenation of cis-2-hexenylamine, which also produces only allylic alcohol product, is only 14% of that for CyHEA. Similarly, kinact./KI for turnover-dependent inactivation by the acyclic olefin 2-aminomethyl-1-pentene is more than an order of magnitude smaller than that for benzylic olefins. Our results establish that DBM catalyses allylic oxygenation of a number of non-conjugated olefinic substrate analogues with neither epoxidation nor allylic rearrangement occurring. The absence of epoxide products from non-conjugated olefinic substrates implies an inability of the activated copper-oxygen species of DBM to effect radical cation formation from a non-conjugated olefinic moiety. The striking contrast between DBM and cytochrome P-450, which carries out both epoxidation and allylic oxidation with non-conjugated olefinic substrates, is probably a reflection of the differences in redox potential of the activated oxygen species operative for these two enzymes. PMID- 7864834 TI - Metabolism of 4-hydroxy-2-nonenal and aging. AB - Hepatocytes isolated from male Wistar rats of 2-3 and 20-24 months of age were compared as regards concentration and metabolism of 4-hydroxy-2-nonenal, one of the major aldehyde products of n-6 fatty acid oxidative breakdown. A significant accumulation of fluorescent 4-hydroxy-2-nonenal-membrane lipid adducts was found in the cells from the old rats. The mechanism mainly responsible for such aldehyde accumulation was shown to be the impairment of its enzymatic metabolism. In fact, while endogenous, that is non-stimulated, aldehyde production was not impaired, the reductive pathway of 4-hydroxy-2-nonenal metabolism in hepatocytes from old rats was strongly depressed. The decrease of 4-hydroxy-2-nonenal consumption with age was confirmed in homogenates from liver and kidney, while there were no differences between young and old animals in heart, lung or brain. PMID- 7864835 TI - Inhibition of human ovarian carcinoma cell proliferation by liposome-plasmid DNA complex. AB - Anti-cancer gene therapy should ultimately lead to specific growth inhibition and loss of tumorigenicity of the tumor cells. Therefore, when using cationic liposomes as DNA delivery systems, it is essential to know how the liposome plasmid DNA complex itself influences the cell growth. This paper reports on the finding that liposome-plasmid DNA complexes specifically inhibited proliferation of human ovarian carcinoma cells, in vitro and in vivo. This inhibiting activity is likely to be sequence independent, since it was observed using several different plasmids. The degree of growth inhibition appeared dependent on both the lipid to DNA ratio and the total dose of liposome-plasmid DNA complex given to the cells. PMID- 7864836 TI - Characterization of the resonance energy transfer couple coumarin-BODIPY and its possible applications in protein-lipid research. AB - In our search for suitable resonance energy transfer (RET) couples for studying protein-lipid interactions, the promising couple coumarin-BODIPY was found and characterized. We characterized the RET from the donor coumarin to two different dipyrrometheneboron difluoride (BODIPY)-labeled phospholipid analogs both experimentally and theoretically. Calculations using the spectral overlap revealed a Forster energy transfer radius (RO) of 50 +/- 2 A and 40 +/- 2 A for the coumarin-(beta-BODIPY FL C12-HPC) and the coumarin-(beta-BODIPY 530/550 C12 HPC) couple respectively. Experimentally this was estimated to be 49.0-51.5 A and 38.5-42.5 A respectively. The use of this couple for studying protein-lipid interactions is exemplified by measurements on a bacterial precursor protein. PMID- 7864837 TI - The use of glycerol to link DNA damage from hydroxyl radicals with the activities of DNA repair enzymes. AB - We show that glycerol can be used to study the relationship between DNA damage caused by hydroxyl radicals and the activities of different DNA repair enzymes. We suggest that such tests with glycerol will lead to a better understanding of the mechanistic basis for radiation-induced cell death, as well as provide valuable information on the specific roles of different DNA repair enzymes. PMID- 7864838 TI - Evidence for a ligand receptor system mediating the biologic effects of glycated albumin in glomerular mesangial cells. AB - Mesangial cells cultured with albumin modified by Amadori glucose adducts exhibit decreased proliferation in association with increased elaboration of Type IV collagen. To test the hypothesis that this modulation of mesangial cell biology is linked to ligand binding, we examined renal glomerular mesangial cells for the expression of receptors that interact with Amadori-modified albumin. Murine mesangial cells bound glycated albumin in a dose-dependent and saturable manner, displaying high and low affinity binding sites. Binding of glycated but not nonglycated albumin was inhibited by monoclonal antibodies that specifically react with albumin containing fructosyllysine groups. LDL containing Amadori glucose adducts did not compete with glycated albumin for binding. These results are consistent with ligand selectively of the binding sites for an Amadori modified sequence within an albumin domain and suggest that a ligand receptor system mediates the effects of glycated albumin on mesangial cell proliferation and matrix production. PMID- 7864839 TI - The rat liver ecto-ATPase/C-CAM cDNA detects induction of carcinoembryonic antigen but not the mercurial-insensitive ecto-ATPase in human hepatoma Li-7A cells treated by epidermal growth factor and cholera toxin. AB - The rat liver ectoATPase has reportedly been cloned. The cDNA, a member of the carcinoembryonic antigen (CEA) gene family, was shown to increase aggregation of transfected cells, but ATPase activity was not evaluated. Using this cDNA as a probe to clone the mercurial-insensitive ectoATPase (MI-ectoATPase) of human hepatoma Li-7A cells, the cDNA obtained was that of CEA which has no ATPase activity. The probe also did not detect increased transcription when MI ectoATPase activity was induced in Li-7A cells. It is concluded that the "rat liver ectoATPase cDNA" codes for a cell adhesion molecule but does not code for an ectoATPase. It was also discovered that expression of four CEA transcripts in Li-7A cells was markedly stimulated by a single growth modulator, EGF, and was further stimulated by a cAMP elevating agent, cholera toxin. PMID- 7864840 TI - Identification of 'molten globule'-like state in all beta-sheet protein. AB - The cardiotoxin analogue III (CTX III), isolated from the Taiwan Cobra venom (Naja naja atra), is a sixty amino acid, all beta-sheet protein. The 2,2,2 trifluoro ethanol (TFE) induced unfolding of CTX III is studied under acidic conditions (pH 2.5). Using circular dichroism, 1-anilino-8-napthalene sulphonic acid binding and NMR experiments, it is shown that stable, partially structured state(s) ['molten globule'-like state] is formed between 50 and 80% TFE concentrations. The protein was found to exist in an unfolded state in 80% TFE containing 2M urea. The TFE induced unfolding process is shown to be completely reversible. In the 'molten globule' state of CTX III in 80% TFE, though portion(s) of the backbone of the protein assume helical conformation, most of the original beta-sheet secondary structural elements in the protein are intact. In our opinion, this is the first report of the identification of a 'molten globule'-like state in the unfolding pathway of an all beta-sheet monomeric protein. PMID- 7864841 TI - Purification and stabilization of mouse DNA methyltransferase. AB - Cytosine methylation within DNA has been implicated in genetic imprinting, X chromosome inactivation, regulation of tissue-specific gene expression, aging, and cancer. Unfortunately, DNA (cytosine-5)-methyltransferases (EC 2.1.1.37) from various mammalian sources have been difficult to isolate and stabilize, precluding investigations of these critical enzymes. We describe a novel FPLC purification of the 190,000 Mr DNA methyltransferase from mouse Friend erythroleukemia cells. The homogeneous 190 kD Mr form of the enzyme is the only polypeptide detected at various stages of cell growth and has not undergone detectable N-terminal proteolysis. PMID- 7864842 TI - Organization of human phospholipid transfer protein gene. AB - We have determined the exon/intron organization of the human phospholipid transfer protein gene. The gene, which spans approximately 13.3 kilobases, is comprised of 16 exons. The organization of the phospholipid transfer protein gene strikingly resembles that encoding another plasma lipid transfer protein, the human cholesterol ester transfer protein. The exon-intron junctions in these two genes are highly conserved, with eight out of fifteen junctions interrupting the same codons, while the remaining junctions lie within 5 residues of each other. The similarity in gene structure and homology in coding sequences suggests that these two genes most likely evolved from a common ancestral gene. PMID- 7864843 TI - Novel antagonist to agonist switch in chimeric G protein-coupled alpha-factor peptide receptors. AB - The alpha-factor analog desTrp1,Ala3 alpha-factor (dTA-alpha-factor) acts as an antagonist for both the S. cerevisiae alpha-factor receptor (c-alpha-FR) and the S. kluyveri alpha-factor receptor (k-alpha FR). Chimeric alpha-factor receptors in which a portion (residues 250-303) of the seven hydrophobic segments were derived from the k-alpha FR and the rest from c-alpha FR conferred potent activation of cellular responses by dTA-alpha-factor including induction of FUS1 expression without significantly affecting binding. Chimeric receptors with all hydrophobic segments derived from one receptor did not express sensitivity. We propose that dTA-alpha-factor represents an antagonist that that has an activation energy barrier to activating c-alpha FR and k-alpha FR but which retains a latent potential to act as an agonist. PMID- 7864844 TI - A new genetic test for familial hyperaldosteronism type I aids in the detection of curable hypertension. AB - In Familial Hyperaldosteronism Type I (FH-I, glucocorticoid-suppressible hyperaldosteronism), a curable form of hypertension inherited in an autosomal dominant fashion, the underlying genetic defect is a "hybrid gene" in which 11 beta-hydroxylase gene regulatory elements are fused to the coding region of the aldosterone synthase gene. The detection of this hybrid gene by Southern blotting is time consuming and involves the use of radioactive isotopes. We describe a new, long polymerase chain reaction-based method for detecting the hybrid gene which greatly reduces the time required to obtain a result, avoids exposure of laboratory workers to radioactive materials, and will thereby facilitate the screening of patients for the presence of FH-I. PMID- 7864845 TI - Electron paramagnetic resonance spectral evidence for the formation of a pentacoordinate nitrosyl-heme complex on soluble guanylate cyclase. AB - Nitric oxide (.NO) is an important intercellular signaling agent throughout the animal kingdom. The majority of the effects of .NO is due to the direct stimulation of soluble guanylate cyclase (sGC). It has been proposed that .NO activates sGC by interacting with a heme moiety on the enzyme. The electron paramagnetic resonance (EPR) spectra of the ferrous-[14N/15N]nitrosyl complexes of the purified enzyme have been obtained. The spectrum of the [14N]nitrosyl-sGC complex was almost identical to that of a 5-coordinate. Hyperfine coupling constants and g-values were determined from computer simulations of the EPR spectra. Electronic absorption spectroscopy was used to show that the 5 coordinate nitrosyl complex on sGC forms under conditions that are typically used to assay activation of the enzyme. PMID- 7864846 TI - Different proliferative responses of periportal and pericentral rat hepatocytes to hepatocyte growth factor. AB - Stimulation of DNA-synthesis by HGF was compared in cultured periportal and pericentral hepatocyte populations. Periportal hepatocytes showed a higher maximal stimulation of the BrdU labeling index than pericentral hepatocytes (7 fold vs 4-fold), while the stimulation for total hepatocytes was in between (5 fold). The glutamine synthetase-positive hepatocytes adjacent to the central veins responded much less to HGF than did the pericentral cells in general. These inherent differences in the growth potential of hepatocytes from different lobular localizations may contribute to the enhanced growth of hepatocytes in the periportal zone in normal and regenerating liver. PMID- 7864847 TI - Troponin isoform dependent pH dependence of the Ca(2+)-activated myofibrillar ATPase activity of avian slow and fast skeletal muscles. AB - The effects of acidic pH were examined on the Ca(2+)-sensitive ATPase activity of chicken fast and slow skeletal muscle myofibrils. In both types of myofibrils the Ca(2+)-sensitivity declined on decreasing pH from 7.4 to 6.2, but the slow skeletal muscle myofibrils were found to exhibit a Ca(2+)-sensitive ATPase activity which was more resistant to acidic pH compared to the fast skeletal muscle myofibrils. The results obtained by using a novel method for replacing whole troponin complex in myofibrils provide the first evidence that troponin is responsible for this higher resistibility of slow skeletal muscle myofibrils to acidosis. PMID- 7864848 TI - Characterization of angiotensin II receptor type 2 during differentiation and apoptosis of rat ovarian cultured granulosa cells. AB - We examined the change in the content of angiotensin II (AII) receptor type 2 (AT2) during differentiation and apoptosis of rat ovarian granulosa cells in culture. The AT2 content was not changed by follicle stimulating hormone (FSH), a differentiation factor of granulosa cells, but was markedly increased in FSH-free media. The cells cultured without FSH underwent internucleosomal DNA fragmentation characteristic of apoptosis, which occurs during follicle atresia. AII augmented the increase in the AT2 content in the absence of FSH. This AII induced augmentation was suppressed by the AT2-selective antagonist PD123319 but not by Dup753, an antagonist specific for type 1 receptor, suggesting that AII up regulates the AT2 expression via AT2 itself. These data strongly support the hypothesis that AT2 might modulate the onset and progression of follicle atresia involving apoptosis of granulosa cells. PMID- 7864849 TI - Ceruloplasmin: an endogenous depolarizing factor in neurons? AB - The biological effects of ceruloplasmin have been exclusively ascribed to its roles as a copper carrier and an antioxidant. Although neuronal involvement of ceruloplasmin is closely related to aging and certain neuronal disorders, neuronal effects of ceruloplasmin are unknown and the possible modulation of membrane potential and ion channels by ceruloplasmin has not been investigated. In the present study, the membrane electrical properties of neuroblastoma cells in the presence of ceruloplasmin were studied using the patch-clamp technique. Ceruloplasmin induced a rapid and sustained membrane depolarization. This capacity of ceruloplasmin was abolished either when the copper was removed from ceruloplasmin or when ceruloplasmin was heat-inactivated. The depolarizing effect of ceruloplasmin was not due to an enhanced Ca2+ or Na+ influx but it seemed to result from a reduced K+ efflux since ceruloplasmin significantly inhibited a TEA sensitive delayed rectifier K+ channel. To our knowledge, this is the first report which indicates that ceruloplasmin is an endogenous neuronal depolarizing factor. PMID- 7864850 TI - Estradiol and pregnenolone sulfate could modulate PMA-stimulated and Ca2+/calmodulin-dependent synaptosomal membrane protein phosphorylation from rat brain in vivo. AB - We have examined the effect of two steroids, pregnenolone sulfate and 17-beta estradiol, on the activity of two protein kinases: protein kinase C and Ca2+/calmodulin-dependent protein kinase. The activity of the kinases was evaluated as phosphorylation of two synapsins Ia and Ib in cerebral cortex and hippocampus of the rat brain. Both steroids decreased phosphorylation of both synapsins to a great extent; however, in hippocampus neither pregnenolone nor estradiol influenced the reaction catalyzed by Ca2+/calmodulin-protein kinase. In the remaining areas of the brain estradiol decreased the activity of both studied kinases to a greater degree than pregnenolone sulfate. Our study suggests that pregnenolone sulfate and 17-beta-estradiol could modulate directly Ca2+/calmodulin-dependent protein kinase and protein kinase C and thus directly influence processes of neurotransmission. PMID- 7864851 TI - Genotype and phenotype of severe mitochondrial cardiomyopathy: a recipient of heart transplantation and the genetic control. AB - Comprehensive analyses of mitochondrial (mt)DNA of a recipient of heart transplantation at age 7 because of severe cardiomyopathy revealed three germ line point mutations, each one in the 12S rRNA gene, in the CO1 gene and in the cytochrome b gene, respectively. As the somatic mutation, extensive fragmentation of mtDNA associated with 212 kinds of deletions was detected in contrast to 5 kinds in an age-matched negative control. A recipient's positive control having almost the same base-substitutions and mutations with the recipient except one in the CO1 gene also developed severe cardiomyopathy died at age 20. The close relation between phenotype and mtDNA genotype provides the basis of our understanding of cell death and premature ageing. PMID- 7864852 TI - Copper binding to the N-terminal tandem repeat regions of mammalian and avian prion protein. AB - Mammalian prion protein (PrP) is a normal cellular protein (PrPc) which through post-translational modification produces the infectious prion protein (PrPsc). We have shown, using mass spectrometry, that synthetic peptides containing three or four copies of an octapeptide repeat sequence (PHGGGWGQ), found in a highly conserved N-terminal domain of PrP, preferentially bind copper over other metals. Peptides from the analogous region of chicken PrP, which contains an N-terminal repeat domain of the hexapeptide (NPGYPH), showed similar specificity for copper binding. In addition, gel filtration chromatography demonstrated concentration dependent binding of copper to the mammalian tetra repeat PrP peptide. These results suggest that PrP may be a copper binding protein in vivo. PMID- 7864853 TI - A permanent glial precursor cell line, immortalized with the adenovirus E1A gene, undergoes apoptosis in restrictive growth conditions. AB - We have previously described some differentiation properties of the ERD.1.1 cell line, obtained after transfer and integration of the adenovirus-5 E1A gene. Depending on the growth conditions, these cells differentiate towards the astrocyte or early oligodendrocyte differentiation pathway. However, in growth restrictive conditions, we observed dying cells that detached from the monolayer constituted of differentiating cells. This led us to examine the characteristics of the dying cells. The study of the low-molecular-weight DNA and the ultrastructural examination of chromatin showed that these cells were undergoing apoptosis. The results also suggest that the expression of an integrated polyoma middle T gene can partly save the cells from apoptosis. PMID- 7864854 TI - Viable rat Kupffer cells synthesize but do not secrete interleukin-1: indications for necrosis-induced maturation of interleukin-1 alpha, but not of interleukin-1 beta. AB - Interleukin-1 is involved in host defense to infection and injury. In this work synthesis and secretion of IL-1 by cultured rat liver macrophages (Kupffer cells) in response to lipopolysaccharide were investigated. IL-1 was found only intracellularly as 31-kD (pro-IL-1 alpha) and 34-kD (pro-IL-1 beta) proteins. No mature 17-kD IL-1 alpha or IL-1 beta was detected in cell lysates or supernatants. Pulse-chase experiments showed that there was no release of IL-1 even after 24h, although pro-IL-1 continuously disappeared from the cells. Cultures were lysed by freezing-thawing. Pro-IL-1 beta was then found in the supernatants, but pro-IL-1 alpha was processed into several smaller fragments. A 17-kD protein could represent the mature IL-1 alpha. The results indicate that Kupffer cells are not able to secrete biologically active mature IL-1 proteins. By lysis of the cells. IL-1 is released. Pro-IL-1 alpha is processed, but pro-IL 1 beta seems to need further activation processes. PMID- 7864855 TI - The role of prohormone convertases PC1 (PC3) and PC2 in the cell-specific processing of proglucagon. AB - To elucidate the mechanism of the differential processing of proglucagon, we analyzed the processing products of proglucagon in three types of rodent endocrine cells and their relation to prohormone convertases PC1 (PC3) and PC2. Proglucagon gene was transfected into AtT-20 cells and GH3 cells, which are derived from pituitary tumors. InR1-G9 cells, which are insulinoma-derived cells, express an endogenous proglucagon gene. Oxyntomodulin was the predominant processing product in AtT-20 cells, which contained abundant PC1 mRNA. In contrast, glucagon was the major product in GH3 cells, which expressed PC2 mRNA. Oxyntomodulin and glucagon were produced in equal amounts in InR1-G9 cells, which expressed both PC1 and PC2 mRNAs. These findings suggest that PC1 and PC2 preferentially cleave proglucagon into oxyntomodulin and glucagon, respectively, thus contributing to the cell-specific processing of proglucagon. PMID- 7864856 TI - An examination of the source of the tyrosyl radical in ovine prostaglandin endoperoxide synthase-1. AB - A tyrosyl radical, which may initiate the cyclooxygenase reaction, has been detected in prostaglandin H synthase by electron paramagnetic resonance spectroscopy. In the crystal structure of ovine prostaglandin H synthase-1, Tyr348 and Tyr385 are in close proximity to the heme. We mutated these residues to phenylalanine to test for their involvement in tyrosyl radical formation. Native enzyme formed a tyrosyl radical centered at g = 2.0036 with a width of 28 gauss. The Y348F mutant formed a singlet signal similar to that of native enzyme with a width of 28 gauss (g = 2.0039). In contrast, the radical signals seen with the Y385F and Y348F/Y385F mutants were 23 gauss (g = 2.004) and 22 gauss (g = 2.0037). In short, tyrosyl radicals are formed even in the absence of both Tyr348 and Tyr385. In Y345F containing mutants, a cluster of aromatic amino acids which surrounds the heme group may provide an alternate pathway for electron abstraction from a more distant tyrosine, yielding a narrow tyrosyl radical signal. PMID- 7864857 TI - Inhibition of mitochondrial permeability transition by polyamines and magnesium: importance of the number and distribution of electric charges. AB - The protective effects of Mg2+ and various natural and synthetic polyamines on the permeability transition of isolated rat liver mitochondria have been compared. The permeability transition was induced by incubating the mitochondria in a sucrose medium at pH 7.4 in the presence of 100 microM Ca2+ and 1 mM phosphate and was monitored via the release of endogenous Mg2+, sucrose permeation, mitochondria swelling and the fall of transmembrane potential. By all of these parameters (only the traces of delta psi have been reported) spermine fully inhibited the transition at 25 microM concentration, spermidine and caldine at 250 microM and Mg2+ at 500 microM concentration. Both putrescine and dien exhibited only a partial protection even at 2.5 mM concentration. The protective action resulted strictly dependent on the number of the positive charges of each cation. In the case of polyamines this number is also determined by the nature of the methylene carbon chains of each compound. PMID- 7864858 TI - Subtypes of endothelin ETA and ETB receptors mediating tracheal smooth muscle contraction. AB - In the isolated rabbit trachea, endothelin (ET)-1, ET-3 and the selective ETB receptor agonists, IRL 1620 and sarafotoxin S6c (STXc), induced contraction with EC50 of 2-9 nM. An ETA1 receptor antagonist, BQ-123, was ineffective whereas desensitization of the ETB receptor strongly antagonized the effect of ET-3, IRL 1620 and STXc. An ETB1 receptor antagonist, RES-701-1, antagonized the effects of ET-3 and IRL 1620 whereas the effect of STXc was antagonized by an ETB2 receptor antagonist, BQ-788. In the ETB-desensitized trachea, only ET-1 induced large contraction that was partially antagonized by BQ-123. These results suggest that ET induces tracheal contraction by activating multiple ET receptors: the ET-1 selective ETA (BQ-123-sensitive ETA1 and insensitive ETA2 subtypes) and the isopeptide-nonselective ETB receptors (RES-701-1-sensitive ETB1 and insensitive ETB2 subtypes). PMID- 7864859 TI - Selective proteolitic activation and degradation of ETs and big ETs in parenchymal strips of the guinea-pig lung. AB - Human and porcine big ET-1 and big ET-2 are similarly potent in contracting parenchymal strips of the guinea-pig lung while big ET-3 is inactive, suggesting that the endothelin-converting enzyme (ECE) which converts big ET-3 is not present and that at least two distinct ECE activities exist, one selective for big ET-1 and big ET-2 and one for big ET-3. Metalloendoprotease inhibitors (phosphoramidon and DL-thiorphan), but not captopril, inhibited the contractions elicited by human big ET-1 and big ET-2 but DL-thiorphan was less active, suggesting that a non-selective enzymatic process is involved in conversion of big ET-1 and big ET-2 in addition to a phosphoramidon-sensitive ECE. Big ET-1 and big ET-2 induced much higher contractions than their corresponding mature peptides. Both metalloendoprotease inhibitors, but not captopril, similarly potentiated contractions induced by ET-1, ET-2 or ET-3 to the level of those evoked by big ET-1 and big ET-2, indicating that only mature ET isopeptides and not their precursors are susceptible to degradation by metalloendoproteases. PMID- 7864860 TI - The GS domain of the transforming growth factor-beta type I receptor is important in signal transduction. AB - Signal transduction by transforming growth factor-beta (TGF-beta) involves the formation of a heteromeric complex of two transmembrane serine/threonine kinase receptors, type I (T beta R-I) and type II (T beta R-II). In the region preceeding the kinase domain of T beta R-I there is a glycine- and serine-rich sequence, termed the GS domain, which has been shown to be phosphorylated by T beta R-II. In order to determine the importance of the serine residues in this domain, receptor mutants with one or more serine residues mutated were analyzed. All the mutants of T beta R-I were able to bind ligand and their kinase activity was not abolished by the mutations. The receptor mutants with single mutated serine residues mediated transcriptional responses to TGF-beta with similar efficiency as the wild type receptor, whereas those with two or three of the serine residues mutated showed only weak transcriptional responses. These results suggest that serine residues in the GS domain are important for signal transduction by T beta R-I; however, the signaling activity of T beta R-I does not depend on any particular serine residue in the GS domain, but rather on how many of the serine residues in the region are intact. PMID- 7864861 TI - Inhibition of retinoic-acid-induced gene expression by 2,3,7,8-tetrachlorodibenzo p-dioxin. AB - The polychlorinated aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly referred to as dioxin or TCDD, has been shown to cause cleft palate in mice. TCDD displays an interesting interaction with another cleft palate teratogen, retinoic acid (RA): when mice are treated with TCDD and RA simultaneously, palatal clefts can be observed in 100% of offspring of mothers at dose levels far below those required for either agent to produce clefting if given singly. This synergy strongly suggests that the pathways controlled by these agents converge at one or more points in cells of the developing palate. In this study, we examined the effects of TCDD on induction of the type II cellular retinoic acid binding protein (CRABP-II) and the retinoic acid receptor beta (RAR beta) by RA in murine embryonic palate mesenchyme (MEPM) cells. While TCDD alone had no effect on basal levels of expression of either gene, the induction of both genes by RA was strongly inhibited by TCDD. These results represent the first evidence for a direct molecular interaction between the RA and TCDD-mediated signaling pathways. PMID- 7864862 TI - Solution structure of omega-conotoxin MVIIC determined by NMR. AB - The solution structure of the P- and Q-type Ca2+ channel blocker, omega-conotoxin MVIIC (a peptidic neurotoxin composed of 26 amino acid residues), has been determined by 1H-NMR and simulated annealing calculations. The resulting calculated structures converged very well to a conformation with an average value of pairwised RMSD for N, C alpha and C' of 0.62 A. Lys-25 is buried in the molecule and less flexible so that among the four Lys residues, its side chain provides the lowest reactivity on biotinylation and the mono-biotinylation in this residue less influences the biological activity. PMID- 7864863 TI - Molecular cloning of an isoform of phenol sulfotransferase from human brain hippocampus. AB - Sulfate conjugation by sulfotransferases is important for the metabolism of drugs, xenobiotics, monoamines, and neuropeptides (1-3). In this study, molecular cloning resulted in the isolation of a 1.2-kb human brain hippocampal cDNA encoding a member of the phenol sulfotransferase (PST) family of enzymes. The hippocampal phenol sulfotransferase (H-PST) cDNA possesses differences in its deduced primary sequence compared to human liver monoamine (M form) (4,5) and phenol (P form) (6,7) isoforms of PST. The hippocampal PST contrasts with previous studies that identified two human brain PST cDNAs whose coding sequences are identical to the human liver M and P forms of PST. Importantly, this study provides evidence for a human hippocampal form of PST. PMID- 7864864 TI - 3-Aminobenzamide protects cells from UV-B-induced apoptosis by acting on cytoskeleton and substrate adhesion. AB - 3-aminobenzamide (3-ABA) is an inhibitor of poly-(ADP-ribose)-polymerase, an enzyme involved in numerous subcellular processes, including cell death. Recently, a target effect of the drug on some cytoskeletal elements has also been described (Malorni et al., Biochem. Biophys. Res. Commun. 202: 915-922, 1994). In this study we evaluated the ability of 3-ABA to interfere with UV-B ray-induced apoptosis in cells selected for their cytoskeletal features and their different capability to adhere to the substrate. Human melanoma (M14) and epithelial (A431) cell lines and murine primary fibroblastic cultures (MFC) were studied. Our results indicate that cytoskeleton is indeed an important cellular target of 3 ABA, which can prevent apoptotic cell death by UV-B through a specific effect on the adhesion properties of the cells. Indeed, an inverse correlation was observed between sensitivity to UV-B-induced apoptosis (M14 > A431 > MFC) and substrate adhesion (MFC > A431 > M14). The potential relevance of these observations to understand the possible relationships among apoptosis, cytoskeletal functions and substrate adhesion is discussed. PMID- 7864865 TI - Characterization of endothelin receptors mediating rat hepatic stellate cell contraction. AB - Hepatic stellate cells (Ito cells) are perisinusoidal cells with features typical of tissue pericytes which have been implicated in the modulation of sinusoidal blood flow. They possess endothelin (ET) receptors and contract in response to ETs. To elucidate the role of ET receptors in stellate cell contraction, a model cell contraction system was used to examine the effect of ET-1, ET-3, sarafotoxin S6C (a pure ETB receptor agonist) and ETA and/or ETB receptor antagonists. ET-1 and sarafotoxin S6C elicited similar contractile responses (EC50 0.18 and 0.21 nM, respectively). BQ-123, an ETA antagonist, minimally inhibited ET-1 induced contraction, while bosentan, a mixed, nonpeptide ETA/ETB antagonist, inhibited ET 1 and sarafotoxin S6C mediated contraction in a similar fashion. In contrast, bosentan had little effect on ET-3 stimulated contraction. The data demonstrate that the ETB receptor is a prominent mediator of stellate cell contraction and raise the possibility of a novel ET receptor subtype. PMID- 7864866 TI - Phosphorylation of the inhibitor-2 of protein phosphatase-1 by cdc2-cyclin B and GSK3. AB - cdc2-cyclin B activates protein phosphatase-1 (PP1) "in vitro", phosphorylates both catalytic subunit and inhibitor-2 (I2) and both processes are inhibited by a cdc2-inhibitory peptide. We compared the phosphorylation of I2 by cdc2-cyclin B and by the PP1-activator Glycogen Synthase Kinase 3 (GSK3). Each kinase introduced less than 0.1 mol phosphate/mol into I2 bound to PP1 and the same two tryptic phosphopeptides were obtained from I2, which contained phospho-T only. The same results were obtained also with isolated I2 phosphorylated by GSK3. Since GSK3 phosphorylates only T-72, cdc2-cyclin B is also likely to phosphorylate this site. This was confirmed by using I2 that had been mutated at this site. On the other hand cdc2-cyclin B introduced up to 0.8 mol/mol phosphate into isolated I2 and four phosphopeptides were obtained. The two new peptides contained phospho-T and one of them also phospho-S. These data indicate the presence of at least one T and one S that are phosphorylated only by cdc2-cyclin B and are accessible on isolated I2 only. PMID- 7864867 TI - Identification of a casein kinase activity found elevated in human cytomegalovirus transformed cells. AB - Protein phosphorylation plays an important role in the regulation of cellular growth and proliferation and is thus thought to play a role in tumorigenesis. It has previously been reported that cells transformed by human cytomegalovirus (HCMV) contain two to four fold higher than normal levels of protein phosphorylation on serine and threonine residues, and two to six fold higher than normal levels of a casein kinase activity. We have now identified the major casein kinase activity found elevated in HCMV transformed cells as casein kinase type II; identification of this kinase was necessary in order to begin to define its role in HCMV mediated morphological transformation. Most of the differences in casein kinase II activity between normal and HCMV transformed cells were explained by differences in casein kinase II protein levels. This represents the first report concerning the elevation of casein kinase II activity in cells transformed by human cytomegalovirus. PMID- 7864868 TI - Putative membrane fatty acid translocase and cytoplasmic fatty acid-binding protein are co-expressed in rat heart and skeletal muscles. AB - A membrane protein (FAT) homologous to CD36 has recently been implicated in the binding and transport of long-chain fatty acids (FA). Expression of this protein in rat heart, skeletal muscles and in isolated cardiac cells was studied. Changes in expression during development of the heart were also examined. Expression of FAT was compared to that of the cytoplasmic fatty acid-binding protein (H-FABP) to determine whether coexpression, indicative of related biological functions, could be demonstrated. FAT and H-FABP mRNAs showed a similar muscle tissue distribution and similar cellular localization in the heart. During development, heart mRNA levels for both proteins were upregulated in the same way. In conclusion, expression of FAT and H-FABP in muscle tissues and cell-types with high FA metabolism and the upregulation of mRNA levels associated with heart development, when FA utilization increases, support the suggested role of both proteins in FA metabolism. PMID- 7864869 TI - Detection and characterization of apoptosis in osteoclasts in vitro. AB - Morphological changes of nuclei and DNA fragmentation undergoing cell death were studied using highly purified rabbit osteoclasts in vitro. Approximately fifty percent of dead osteoclasts exhibited morphological changes of nuclei characterized by apoptosis and approximately 70% of osteoclasts with changes of nuclei exhibited DNA fragmentation in our culture system. These changes of nuclei were confirmed as condensation of chromatin through transmission electronmicroscope. Moreover, biochemical characterizations of these changes were compatible with the characterizations of apoptosis in other cell systems. These results demonstrate that part of osteoclasts die by a mode of apoptosis. PMID- 7864870 TI - C/EBP alpha expression in adipose tissue of genetically obese Zucker rats. AB - The adipose tissue of genetically obese Zucker rats is characterized by coordinated tissue specific overtranscription of a subset of genes related to lipid storage such as Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH). We show that CCAAT/Enhancer Binding Protein alpha (C/EBP alpha) is an activator of GAPDH proximal promoter in transiently transfected mature rat adipocytes. C/EBP alpha mRNA levels were increased in adipose tissue but not in liver of obese as compared to lean rats at 30 days of age, i.e., when obesity is fully expressed. Nevertheless at 16 days of age, although overdevelopment of adipose tissue could be detected in preobese rats, C/EBP alpha mRNA levels were similar whatever the genotype. In conclusion C/EBP alpha mRNA is overexpressed in adipose tissue of obese rats, suggesting a possible role for this factor in the activation of lipid storage-related genes in adipose tissue of obese rats. However, C/EBP alpha overexpression is not temporally related to the onset of obesity. PMID- 7864871 TI - Exogenous triacylglycerol inhibits insulin-stimulated glucose transport in L6 muscle cells in vitro. AB - This study tested the hypothesis using cultured L6 myocytes that insulin resistance in muscle may be the consequence of triacylglycerol accretion in the tissue itself. Exposure of L6 myocytes to triacylglycerol for 4 hours resulted in significant transfer of lipid into the cells compared to control cells treated for only 5 min. Insulin-stimulated 2-deoxyglucose uptake in L6 myocytes was reduced when the cells were preloaded with triacylglycerol. Insulin-independent and insulin-stimulated 2-deoxyglucose uptake were inhibited by cytochalasin B, indicating that both were transporter-mediated. Diacylglycerol mimicked insulin action by increasing 2-deoxyglucose uptake and this was also reduced by triacylglycerol preloading, suggesting that the effect was not mediated at the insulin receptor. Thus, triacylglycerol may exert a direct effect on muscle cell insulin sensitivity possibly at the level of diacylglycerol second messenger pathway. PMID- 7864872 TI - Occurrence of glutathione-modified aldose reductase in oxidatively stressed bovine lens. AB - The optimization of an affinity chromatography method on Matrex Orange resin allowed the separation of glutathione modified and native aldose reductase in crude extracts of bovine lens. The analysis of hyperbaric oxygen treated lenses revealed the formation in the intact cultured lens of an enzyme form displaying affinity column binding properties, specific activity, sensitivity to inhibition and susceptibility to activation by thiol reducing agents, all comparable to glutathione modified aldose reductase. The extent of the enzyme modification increased with the time of the oxidative treatment and was maximal in the lens nucleus. The relative increase of glutathione modified aldose reductase from cortex to the nucleus is consistent with the increase in these lens regions of the GSSG/GSH ratio. PMID- 7864873 TI - High-yield bacterial expression, purification, and functional reconstitution of the tricarboxylate transport protein from rat liver mitochondria. AB - The rat liver mitochondrial tricarboxylate transport protein has been overexpressed in E. coli. The expressed transporter, which contains a 21 amino acid N-terminal fusion sequence, accumulates in inclusion bodies. Subsequent extraction of the tricarboxylate transporter from isolated inclusion bodies yields approximately 90 mg of transport protein per liter of E. coli culture at a purity of greater than 90%. Upon incorporation into phospholipid vesicles the purified, overexpressed transporter catalyzes a 1,2,3-benezenetricarboxylate sensitive citrate/citrate exchange (i.e., the defining reaction of the mitochondrial tricarboxylate transporter). Kinetic characterization of the reconstituted transporter indicates a Km of 0.37 mM and a Vmax of 101 nmol/min/mg protein. The substrate specificity of the reconstituted, expressed transporter is virtually identical to that of the native transporter. These studies represent the first overexpression of the rat liver mitochondrial tricarboxylate transporter. By providing a large amount of highly-purified, functionally competent transporter this system will now enable a variety of structural studies, including site-directed mutagenesis, which heretofore could not be performed. PMID- 7864874 TI - Cloning of a cDNA coding for porcine zona pellucida glycoprotein ZP1 and its genomic organization. AB - The zona pellucida composed of three or four glycoproteins plays important roles in fertilization. Our previous study showed that porcine ZP1, one of the major glycoproteins of porcine zona pellucida, was divided into two components (porcine ZP4 and ZP2), and suggested it was a homologue of mouse ZP2. In this paper we report the cloning of a cDNA for porcine ZP1 and its genomic organization. The deduced amino acid sequence of porcine ZP1 shared a 54% and 63% identity with those of mouse and human ZP2, respectively. Genomic organization of porcine ZP1 was also similar to that of mouse ZP2. The transcript of porcine ZP1 gene was detected only in growing oocytes. PMID- 7864875 TI - Detection of messenger RNA for gonadotropin-releasing hormone (GnRH) but not for GnRH receptors in mouse mammary glands. AB - While gonadotropin-releasing hormone (GnRH), GnRH-like, or GnRH receptor (GnRH-R) have been reported to exist in several tissues other than brain or anterior pituitary, there is no report concerning GnRH or GnRH-R gene expression in the normal mammary gland. In order to define the production of GnRH as well as GnRH-R in the mammary gland at the molecular level we examined their gene expression in various functional stages of the mouse mammary gland using the reverse transcriptase-polymerase chain reaction (RT-PCR). GnRH mRNA transcripts were found in mouse mammary glands of mid-pregnant, lactating, and 3, 6, 9 days post lactational mice, whereas GnRH-R mRNA transcripts were not detected in mammary glands of any functional stage. These results suggest a possible biological role of GnRH in mammary gland. PMID- 7864876 TI - Cloning and functional expression of human endothelin-converting enzyme cDNA. AB - Endothelin (ET) is a 21-residue potent vasoconstrictive peptide produced by vascular endothelial cells and formed from its precursor, big endothelin (big ET), by endothelin-converting enzyme (ECE). This paper describes the cloning and functional expression of a cDNA encoding a human ECE from human umbilical vein endothelial cells (HUVEC). Human ECE consists of 758 amino acid residues and has high homology to rat and bovine ECE. Immunoblot analysis using a monoclonal antibody risen against rat lung ECE showed the presence of immunoreactive protein in membrane fraction prepared from both HUVEC and COS-1 cells transfected with human ECE cDNA. Both COS-1 cells expressing human ECE and its membrane fraction converted big ET-1 most efficiently among big ETs. PMID- 7864877 TI - Polymeric precipitants for the crystallization of macromolecules. AB - Nine different water soluble polymers reported to strongly affect the properties and structure of water were evaluated for their use in crystallizing a series of 24 different proteins, viruses, and conventional small molecules. All of the polymers produced crystals of some of the molecules and viruses tested, and of the 24 molecules tested, 14 were crystallized. In a number of cases, crystals of the molecules and viruses were obtained under very different conditions than were ever previously used. Because the selection of polymers employed here represents only a sampling of those available to experimenters, we conclude that the potential range of such polymers useful in macromolecular and small molecule crystallization may be very broad. PMID- 7864878 TI - Impaired growth response to endothelin-1 in scleroderma fibroblasts. AB - Systemic sclerosis (SSc) is characterized by vascular damage and dermal fibrosis. In this study, we examined the endothelin (ET) receptor subtype involved in mitogenic signaling in scleroderma and normal skin fibroblasts. ET-1 stimulated DNA synthesis of normal fibroblasts in serum-deprived cultures. ET-3 had lesser effects on DNA synthesis of normal fibroblasts than ET-1. The growth response to ET-1 in scleroderma fibroblasts was decreased compared to normal fibroblasts. [125I]-ET-1 binding to normal fibroblasts was significantly blocked by excessive amount of unlabeled ET-1 and BQ-123. [125I]-ET-1 binding to scleroderma fibroblasts was significantly decreased compared with normal controls. Immunoblotting analysis showed that the expression of ETA receptor in scleroderma fibroblasts was diminished compared with normal controls. ETA mRNA expression in scleroderma fibroblasts was decreased compared with that of normal fibroblasts. From these results, we conclude that the mitogenic effects of ET in human dermal fibroblasts are mainly mediated through ETA receptors, and that down-regulation of ETA receptors caused the decreased growth response of ET-1 in scleroderma fibroblasts. PMID- 7864879 TI - Mitochondrial DNA deletion analysis: a comparison of PCR quantitative methods. AB - The role of mitochondrial DNA (mtDNA) deletions in aging and in neurodegenerative diseases is often determined by measuring the amount of deleted mtDNA in the affected tissue. Upon examining brain autopsy tissue from a 59 year old individual with lung cancer we determined by serial dilution PCR and kinetic PCR that a greater ratio of deleted mtDNA was present in the caudate than in the parietal cortex. However, the magnitude difference for these two brain regions appeared to be technique dependent; by serial dilution PCR the caudate had 10 times more deleted mtDNA than the parietal cortex (0.0141 vs 0.0014) whereas kinetic PCR yielded a 4-fold difference (0.1258 vs 0.0316). These results indicate that although it is valid to compare the amount of deleted mtDNA in normal and diseased tissue and draw conclusions based on relative comparisons within one study, greater caution should be exercised when comparing absolute values from studies using different measurement techniques. PMID- 7864880 TI - SECReT of the eukaryotic large ribosomal subunit. AB - The large ribosomal subunit of the thermophilic fungus Thermomyces lanuginosus was reconstructed in three dimensions from electron micrographs. This is the first reported reconstruction of the eukaryotic complex and demonstrates specific structural features such as an intersubunit canyon and a potential channel for the nascent peptide chain. PMID- 7864881 TI - Onco-fetal/laminin-binding collagen from colon carcinoma: detection of new sequences. AB - We have recently identified an oncofetal-laminin binding collagen (OF/LB) composed of three alpha chains, with the apparent molecular mass of about 100 kDa each, but bearing different pI. One of the chains appears markedly acidic in a bidimensional electrophoretic system, where the NEPHGE is used as first dimension separating gel, while the two more basic chains have similar migration as alpha 1(III) and alpha 1(I) collagen chains, respectively. Sequence analyses have been performed on CNBr-peptides, derived from pepsinized triple helical molecules and on tryptic fragments obtained after in gel digestion of the acidic band. The research of sequence homology with computerized databases indicated that the acidic chain represents a gene product distinct from either type I, type III and other known collagen chains, while the identity of the other two chains remains to be fully determined. PMID- 7864882 TI - Involution of mouse mammary glands in whole organ culture: a model for studying programmed cell death. AB - The DNA fragmentation and gene expression patterns of involuting mouse mammary glands were compared to mammary glands in whole organ culture induced to involute by the withdrawal of lactogenic hormones. Non-random DNA degradation was observed both in vivo and in vitro, indicating that the withdrawal of lactogenic hormones triggers a program of epithelial cell death. Similar patterns of gene expression for the milk protein beta-casein and the apoptosis associated factors TGF-beta 1, TGF-beta 2 and TGF-beta 3 were observed in vivo and in vitro. These results indicate that the withdrawal of lactogenic hormones is responsible for decreased milk synthesis, epithelial cell death and tissue restructuring and that whole organ culture of mouse mammary glands is a useful model for studying the molecular events involved in these processes during involution. PMID- 7864883 TI - Amino-terminal palmitate or polybasic domain can provide required second signal to myristate for membrane binding of p56lck. AB - Recent work has shown that several members of the src family of protein tyrosine kinases (PTKs) are modified by palmitoylation, including p56lck and p59fyn but not p60src. Mapping of the sites of palmitoylation in p56lck identified cys3 as the major site and cys5 as a minor site of palmitoylation. A non-palmitoylated p56lck(cys3,5-->ser) mutant was localized exclusively in the cytoplasm despite the presence of amino-terminal myristoylation, thus indicating that palmitoylation of p56lck was necessary for membrane binding. The addition of a domain of six lysine residues to a non-palmitoylated p56lck mutant was sufficient to re-establish membrane binding but not to target the non-palmitoylated p56lck to caveolae. These results establish that two signals, myristoylation plus either palmitoylation or a polybasic domain, are necessary for membrane binding of src family PTKs. PMID- 7864884 TI - Interaction of cultured rat osteoblasts with 8-methoxypsoralen during irradiation with long-wave ultraviolet light. AB - Rat osteoblasts in monolayer cell cultures have been irradiated with long-wave ultraviolet light (UVA) in the presence and without 8-methoxypsoralen (8-MOP). In the absence of 8-MOP, the exposures to UVA (3 x 10(-3)W.cm-2) for up to 30 min have not affected cellular viability, the rate of 14C-acetate incorporation, and alkaline phosphatase (AP) activity. However, it depressed 3H-TdR incorporation rates by osteoblasts. In the presence of 15 to 100ng of 8-MOP/ml, even 5-min irradiation of osteoblasts was sufficient to reduce DNA synthesis. Much higher (0.5 to 1.0 micrograms/ml) 8-MOP concentrations were required to depress lipid synthesis, AP activity, and the viability of irradiated cells. These results suggest that in osteoblasts the machinery of DNA synthesis is especially labile to photosensitization with 8-MOP and UVA, whereas UVA light by itself exerts a less potent inhibitory effect. PMID- 7864885 TI - Two distinct K(+)-ATPase activities in rabbit distal colon. AB - The distribution of K(+)-ATPase activity in surface and crypt cells from rabbit distal colon was studied. Separation of surface and crypt cells was validated using the multidrug resistance gene (mdr 1) product, P-glycoprotein, as marker for differentiated surface epithelial cells. Western blot analysis revealed a 6 fold higher expression level of P-glycoprotein in colonic surface cells. K(+) stimulated ouabain-insensitive ATPase activity was present in surface and in crypt cells. In surface cells, this K(+)-ATPase activity was only partly inhibitable by 10 microM SCH 28080, while in crypt cells K(+)-ATPase activity equalled SCH 28080-sensitive ATPase activity. These results strongly suggest the presence of two distinct K(+)-ATPases in colonic epithelial cells. PMID- 7864886 TI - Reversible inactivation of calpain isoforms by nitric oxide. AB - S-nitrosylation by sodium nitroprusside, a nitric oxide-generating agent, inactivates, almost completely at neutral pH, the proteolytic activity of the high Ca2+ requiring calpain form (m-calpain) from skeletal muscle. This inhibition is reversed by treating the inactivated proteinase with dithiothreitol. When exposed to sodium nitroprusside, the single m-calpain-like isoform from human neutrophils is inactivated too. On the contrary, the activities of muscle mu-calpain isoform and the human erythrocyte single mu calpain-like isoform are poorly affected by nitric oxide treatment at neutral pH; however, inactivation is progressively enhanced if the pH of incubation mixtures is shifted to acidic values, a condition which conversely reduces NO-mediated inactivation of m-calpain. On the basis of these results, it is conceivable to postulate that nitric oxide may exert a regulatory role of muscle calpain activity by modulation of either one or the other proteinase isoform, also in concomitance with fluctuations of hydrogen ions in contracting cells occurring in physiological or pathological conditions. The regulatory role of nitric oxide is also supported by the observation that S-nitrosylation induces inactivation of calpain also in intact human neutrophils. Furthermore, the reversibility of the inactivation of calpain by nitric oxide may be exploited to study the relationship between the molecular structure and the catalytic and regulatory mechanisms of this neutral proteinase. PMID- 7864887 TI - Docosahexaenoic acid is a potent inhibitor of rat uterine stromal cell proliferation. AB - The effect of different families of fatty acids on the proliferation of rat uterine stromal cells (UIII) was studied. Docosahexaenoic acid (DHA) exerted a strong and dose-dependent inhibitory effect (IC50 approximately 2 microM), whereas arachidonic acid (AA) stimulated UIII cell proliferation at the optimal concentration of 10 microM. Oleic, linoleic and linolenic acids were ineffective from 0.1 to 10 microM. The inhibitory effect of DHA was independent of the eicosanoid biosynthesis and lipid peroxidation, since it was not reversed by the addition of the antioxidant BHT and no significant production of oxidized species from DHA occurred in our culture conditions. PMID- 7864888 TI - Point mutation of the RET proto-oncogene in the TT human medullary thyroid carcinoma cell line. AB - The RET proto-oncogene encodes a tyrosine-kinase receptor specifically expressed in tissues of neuroectodermal origin. Recently specific point mutations of RET have been demonstrated to be responsible for the Multiple Endocrine Neoplasia type 2A and 2B and Familial Medullary Thyroid Carcinoma syndromes, characterized by the occurrence of medullary thyroid carcinomas. Here we report that a human medullary thyroid carcinoma cell line, the TT cell line, harbours a MEN2A-type mutation, specifically a cysteine to triptophan substitution at the level of the RET codon 634. This mutation is heterozygous and both normal and mutated alleles are expressed. We suggest that the TT cell line could be a useful cell system to investigate the role played by the RET oncogene in the transformation and differentiation of human thyroid C-cells. PMID- 7864889 TI - A cell-cycle nuclear autoantigen containing WD-40 motifs expressed mainly in S and G2 phase cells. AB - Recently a novel nuclear protein mainly expressed in S and G2 phase cells was characterized using autoantibodies from a cancer patient (Exp. Cell Res., 212, 255-261, 1994). cDNA clones were isolated by immunoscreening, and sequence analysis revealed that the cDNA clones encoded a 713-amino acid residue polypeptide which is provisionally named SG2NA (S/G2 nuclear antigen). In the carboxyl terminal half of SG2NA, there are 6 copies of WD-40 motifs characteristic of a large family of proteins of which the prototype is beta transducin/enhancer of split (TLE). In addition, there are nuclear localization sequence and phosphorylation sites related to the TLE proteins. Autoantibodies occurring spontaneously in certain cancer patients have been useful reagents for identifying cellular proteins and this is the first report of a novel WD-40 protein which is the target of an autoimmune response. PMID- 7864890 TI - Phosphorylation of CREB by CaM-kinase IV activated by CaM-kinase IV kinase. AB - Previous reports have shown that CaM-kinase IV can phosphorylate the transcription factor CREB in vitro on Ser133. Furthermore, transfected CaM-kinase IV can activate CREB-dependent transcription, but at a lower efficiency than the cAMP-kinase. In this paper we examine the kinetics and site-specificity of CREB phosphorylation in vitro by CaM-kinase IV after its phosphorylation and activation by a newly discovered brain CaM-kinase IV kinase. Our results show that activated CaM-kinase IV has the same Km (1-5 microM) for CREB phosphorylation, but the Vmax is about 30-fold higher than with non-activated CaM kinase IV. Activated CaM-kinase IV still shows specificity for phosphorylation of Ser133, the site necessary for transactivation by CREB. It is likely that the lower efficiency of transcriptional activation by transfected CaM-kinase IV in previous studies was due to the fact that the CaM-kinase IV was not activated by CaM-kinase IV kinase. PMID- 7864891 TI - Interleukin 8 (IL-8) inhibits the interleukin 4 (IL-4)-induced but not the spontaneous growth of human B cells via mechanisms that may involve protein kinase C. AB - IL-8 inhibited the IL-4-induced but not the spontaneous growth of both a human B cell line, CBL, and in vivo activated B cells. This inhibition was specific to IL 8, since anti-IL-8 mAb, but not control IgG1, blocked inhibition. Phorbol 12, 13 dibutyrate did not affect the IL-4-induced B cell growth; however, it reversed the IL-8-mediated inhibition, and this reversal was blocked by H7 (a protein kinase C inhibitor), but not by H8 (a protein kinase A inhibitor). These results indicate that IL-8 inhibits IL-4-induced B cell growth via specific mechanisms that may involve protein kinase C. PMID- 7864892 TI - Phosphorylation of the C-terminal domain of RNA polymerase II by the extracellular-signal-regulated protein kinase ERK2. AB - Rat ERK2, an extracellular-signal-regulated protein kinase family member, phosphorylates RNA polymerase II in vitro. Phosphorylation occurs within the heptapeptide repeats of the C-terminal domain of the largest subunit, in a region important for regulation of transcriptional activity. Analysis of deletion mutants and synthetic peptides showed that ERK2 phosphorylation occurs at multiple serine residues throughout the C-terminal domain, with no marked preference for consensus repeats versus naturally occurring variants. Our results are consistent with the idea that protein kinases in the extracellular-signal regulated protein kinase family regulate transcription by direct phosphorylation of RNA polymerase II, but do not support a model where particular portions of the C-terminal domain are special targets of ERK phosphorylation. PMID- 7864893 TI - Human proteasome subunits from 2-dimensional gels identified by partial sequencing. PMID- 7864894 TI - Molecular cloning and functional expression of a human pancreatic secretin receptor. AB - Through binding to high affinity receptors, secretin is the major hormonal stimulant of ductular bicarbonate secretion in the pancreas, contributes toward enzyme secretion from pancreatic acinar cells, and has been implicated as a pancreatic growth factor. In this work, we utilized hybridization screening of a human pancreatic cDNA library to clone a 1.8-kb cDNA encoding a 440 amino acid protein 81% identical to the rat pancreatic secretin receptor. COS-7 cells transfected with this cDNA bound secretin with a high affinity, and vasoactive intestinal peptide with a lower affinity, appropriate for a secretin receptor. Receptor-bearing COS-7 cells also exhibited an increase in cyclic AMP generation in response to secretin stimulation. Studies analyzing the role of this receptor in human pancreatic physiology and pathophysiology are currently underway in our laboratory. PMID- 7864895 TI - Changing the inhibitory specificity and function of Cucurbita maxima trypsin inhibitor-V by site-directed mutagenesis. AB - Cucurbita maxima trypsin inhibitor-V (CMTI-V) is also a specific inhibitor of human blood coagulation factor beta-factor XIIa. A recombinant version of CMTI-V has allowed probing of roles of individual amino acid residues including the reactive site residue, lysine (P1), by site-directed mutagenesis. The K44R showed at least a 5-fold increase in inhibitory activity toward human beta-factor XIIa, while there was no change toward bovine trypsin. This result demonstrates that beta-factor-XIIa prefers an arginine residue over lysine residue, while trypsin is non-specific to lysine or arginine in its binding pocket. On the other hand, the specificity of CMTI-V could be changed from trypsin to chymotrypsin inhibition by mutation of the P1 residue to either leucine or methionine (K44L or K44M). PMID- 7864896 TI - Mode of action and resistance to azole antifungals associated with the formation of 14 alpha-methylergosta-8,24(28)-dien-3 beta,6 alpha-diol. AB - Azole antifungal compounds inhibit sterol 14 alpha-demethylase. They are used extensively for the treatment of immunocompromised patients where fungal infection is common and often results in death. Resistance to the compounds is emerging, particularly in fungal pathogens obtained from AIDS patients undergoing prolonged therapy. We show here that cell growth arrest correlates with the accumulation of 14 alpha-methyl-ergosta-8,24(28)-dien-3 beta,6 alpha-diol in a yeast strain with a sterol 14 alpha-demethylase gene disruption, which mimics stringent treatment conditions. Cells can overcome the effect of such a block by a suppressor mutation in sterol delta 5,6 desaturation and acquire azole resistance. Plasmid-based complementation of sterol 14 alpha-demethylase defect does not alter the azole susceptibility of strains containing these suppressor mutations, showing resistance is due entirely to the delta 5.6 desaturase defect. PMID- 7864897 TI - Phosphorylation of helix-loop-helix proteins ID1, ID2 and ID3. AB - Id is a helix-loop-helix protein which forms heterodimer with ubiquitous and/or tissue-specific basic helix-loop-helix proteins and inhibits their DNA binding. It has been noted that putative phosphorylation sites for various protein kinases exist in rat Id1, Id2 and Id3. We show here that Id1 and Id2 can be phosphorylated in vitro by cAMP-dependent protein kinase, Id2 and Id3 by cdc2 kinase, and all three Ids by protein kinase C. The phosphorylated Id1 was actually immunoprecipitated in nerve-growth-factor-stimulated PC12 cells. Gel mobility shift assays, however, demonstrated that neither phosphorylation of Id proteins by cAMP-dependent protein kinase nor phosphorylation of E47 by protein kinase C affected the inhibition of E47 homodimer formation and its DNA binding. Taken together with other observations, phosphorylation of Id proteins may play a role in regulation of cell differentiation but not directly in the dimerization and DNA binding. PMID- 7864898 TI - Creation of a high cytotoxic active human tumor necrosis factor having the truncated and more basic amino terminus. AB - In order to define the structure-functional relationship of tumor necrosis factor(TNF), a mutant TNF gene was created by site-specific mutagenesis based on the PCR technique. This gene was highly expressed in E.coli cells. The amount of the recombinant protein was up to about 80% of the total cellular proteins. Through one-step ion exchange chromatography, the mutant TNF could be purified to homogeneity. This mutein showed the molecular weight of a dimer but not a trimer. It bears the features of truncated amino terminus and increase of the basicity of amino terminal residues. Compared with the wild type TNF, the specific activity of mutant TNF was increased by fourfold. PMID- 7864899 TI - The functional expression of a rat cDNA encoding OSCP in the yeast Saccharomyces cerevisiae. AB - The oligomycin sensitivity conferring protein (OSCP) of Saccharomyces cerevisiae is a component of the stalk FA sector of the mitochondrial F1Fo-ATP synthase complex (mtATPase). The subunits comprising this sector have been implicated in the coupling of proton flux through the membrane Fo sector to ATP synthesis on the catalytic F1 sector. We tested whether the yeast subunit encoded by the ATP5 gene could be functionally replaced by a mammalian homologue, rat OSCP. The yeast and rat OSCP proteins have 58% homology in terms of conserved amino acids. A vector-borne rat cDNA encoding the OSCP precursor was introduced into a yeast strain lacking endogenous OSCP as a result of its disrupted ATP5 gene. The resultant yeast cells showed essentially a wildtype growth rate at 18, 28 and 35 degrees C, on nonfermentable substrates. Expression of mammalian FA subunit homologues in yeast should provide a productive new approach to generating information on the structure and function of mtATPase. PMID- 7864900 TI - Molecular cloning of a new member of the Rab protein family, Rab 26, from rat pancreas. AB - Members of the Rab family of low molecular weight GTP-binding (LMWG) proteins regulate vesicular transport; distinct Rab proteins are located in specific vesicular compartments within the exocytotic and endocytotic pathway. Pancreatic zymogen granules possess multiple LMWG. Rab 3A, however, which has been suggested to regulate exocytosis of synaptic vesicles, is not present in rat pancreatic acinar cells or on zymogen granules (BBRC 1994,269:542-548). To look for homologues of Rab 3A we have screened a rat pancreatic cDNA library using Rab 3A as a probe. We now report the cDNA and deduced amino acid sequence of a new member of the Rab protein family. Rab 26 is a 190 AA protein with a predicted molecular mass of 21,459 Dalton. It is expressed in pancreas, kidney, brain, submandibular gland, and lung. It is most closely related to Rab 8. There is also close homology to Rab 15, Sec4 and Rab 3. PMID- 7864901 TI - Hydroxyl radicals and DNA double-strand breaks in X-irradiated E. coli. AB - We have used glycerol to study the relationship between hydroxyl radicals, one of the primary radiolytic products, and the production of DNA double-strand breaks in selected E. coli strains. Our results suggest that when bacteria are irradiated at doses up to about 120 Gray, hydroxyl radicals produce DNA lesions, but not double-strand breaks. PMID- 7864902 TI - Transforming growth factor-beta and forskolin increase all classes of insulin like growth factor-I transcripts in normal human osteoblast-like cells. AB - In this study, we examined regulation of insulin-like growth factor I (IGF-I) gene expression and transcript splicing in normal human osteoblast-like cells. Previous studies in rat osteoblastic cells have indicated that transforming growth factor-beta (TGF-beta) inhibits IGF-I expression, whereas inducers of intracellular cAMP stimulate IGF-I expression. However, in human osteoblast-like cells both TGF-beta and forskolin increased IGF-I mRNA levels in a time- and dose dependent manner. All 4 classes of IGF-I transcript that can result from alternate leader exon usage and splicing of the human IGF-I gene were induced proportionally. Although human osteoblasts increase IGF-I mRNA in response to important skeletal regulatory factors, some responses may be species-specific. PMID- 7864903 TI - Secretion of Alzheimer beta/A4 protein (1-40) and intracellular retention of beta/A4 protein (1-42) in transfected COS cells. AB - The amyloid beta/A4 protein (beta/A4) of Alzheimer disease is heterogeneous. A beta 1-40 (Asp1 to Val40) is rather soluble, whereas A beta 1-42 (Asp1 to Ala42) is more insoluble and can be the seed of deposition of A beta 1-40. Although beta/A4 itself could not be expressed transiently in COS cells by cDNA transfection, it was expressed after directly adding a signal sequence to its N terminal end. The expressed A beta 1-40 was secreted, whereas A beta 1-42 was hardly secreted. A beta 1-40 secretion was not inhibited by metabolic inhibitors such as brefeldin A. The normally produced A beta 1-40 could not be retained intracellularly, whereas the abnormally generated A beta 1-42 might be accumulated intracellularly, resulting in cellular toxicity. PMID- 7864904 TI - Isolation and the gene cloning of an alkaline shock protein in methicillin resistant Staphylococcus aureus. AB - The growth of Staphylococcus aureus occurs at a wide range of pH(5-10), while the optimal is pH 7.0-7.5. The molecular mechanism of such pH tolerant properties should be elucidated because the production of the virulence factors was greatly affected by environmental pH. The effect of pH shift on the composition of cytosolic proteins in S. aureus was examined. A protein with a molecular mass of 23 kDa was remarkably enhanced by a pH upshift from 7 to 10. This alkaline shock protein (ASP23) was isolated and purified by ion-exchange chromatography. The N terminal sequences of the purified protein and the protease-digested peptides were analyzed. The 320-bp DNA fragment that was designed from the peptide analysis was amplified. Using the amplified fragment as a probe, the ASP gene, asp23, was cloned. The deduced primary sequence of ASP23 comprised 169 amino acids with a calculated molecular weight of 19,191. Northern analysis revealed that asp23 was positively regulated at the transcription level by alkaline shock. Homology search revealed that asp23 is a novel gene. Although the physiological role of ASP23 has yet to be further analysed, we suggest that ASP23 plays a key role in alkaline pH tolerance of S. aureus. PMID- 7864905 TI - Isolation of Epstein-Barr-virus-transformed lymphocytes producing IgG class monoclonal antibodies using a magnetic cell separator (MACS): preparation of thyroid-stimulating IgG antibodies from patients with Graves' disease. AB - In autoimmune diseases, IgG class autoantibodies are generally considered to be more pathognomonic than IgM class ones. Although Epstein-Barr virus (EBV) transformation of lymphocytes is a useful method to obtain human monoclonal autoantibodies, it tends to result predominantly in IgM-producing cells. We depleted IgM+ cells before EBV-transformation with a Magnetic Cell Separator (MACS) in order to increase the chance of acquisition of cells producing IgG class anti-thyrotropin (TSH) receptor antibodies (TRAb). As a result, we obtained four independent B cell clones producing IgG class monoclonal thyroid-stimulating antibodies (TSAb) from three patients with Graves' disease. None of these clones showed any TSH binding inhibitor immunoglobulin (TBII) activity, suggesting independence of TSAb-producing lymphocytes from those producing TBII. PMID- 7864906 TI - Sideport incision paracentesis versus antiglaucoma medication to control postoperative pressure rises after intraocular lens surgery. AB - Twenty-eight patients who had an intraocular pressure greater than 30 mm Hg within 24 hours after cataract surgery were randomly assigned to be treated with medication or by paracentesis through a sideport incision. Paracentesis provided an immediate reduction in intraocular pressure, but within one hour pressures rebounded. Within two to three hours after treatment, the medication group had significantly greater mean reductions in intraocular pressure than the paracentesis group. PMID- 7864907 TI - Mozart's chronic subdural hematoma. AB - No commemoration of the bicentennial of Mozart's death would be complete without some consideration of that premature yet predictable demise. Mozart's premonitions of death are well known and apparently played a role in the composition of the K.626 Requiem and perhaps other works. His death has traditionally been ascribed to infectious causes, chiefly rheumatic fever or post streptococcal glomerulonephritis, exacerbated by intemperance and chronic penury. Pathology has been difficult because of his supposed burial in a pauper's grave, the location and contents of which were later supposedly lost. Mozart's burial place in St. Mark's Cemetery in Vienna was known and, in the parlance of the day, "reorganized" a decade later, as the occupants of plots were disinterred to make room for the more recently decreased. A skull believed to the Mozart's was saved by the successor of the gravedigger who had supervised Mozart's burial, and then passed into the collections of the anatomist Josef Hyrtl, the municipality of Salzburg, and the Mozarteum museum (Salzburg). Forensic reconstruction of soft tissues related to this skull reveals substantial concordance with Mozart's portraits. The skull suggests premature closure of the metopic suture, which has been suggested on the basis of his physiognomy. A left temporal fracture and concomitant erosions raise the question of chronic subdural hematoma, which would be consistent with several falls in 1789 and 1790 and could have caused the weakness, headaches, and fainting he experienced in 1790 and 1791. Aggressive bloodletting to treat suspected rheumatic fever could have decompensated such a lesion to produce his death on December 5, 1791. PMID- 7864908 TI - Shooting backward with Marcus Gunn: a circular exercise in paralogic. PMID- 7864909 TI - Do anaesthetics and surgical stress increase the risk of post-exposure rabies treatment failure? AB - Rabies is fatal in humans and, after exposure, only correct postexposure treatment as outlined in World Health Organization guidelines can prevent the disease. Analysis of case reports of treatment failures has shown that recommendations have not been followed and that patients presenting risk factors should receive additional care. Known risk factors are delay of more than 24 h in starting postexposure treatment, multiple wounds (especially on head, neck, arm or fingers), incorrect initial wound treatment, immunodepression and non application of anti-rabies immunoglobulins or serum. We present a case, recently reported from India to Drug Surveillance Behringwerke AG, Marburg, Germany, in which surgery under ketamine anaesthesia might have been an additional risk factor for postexposure treatment failure. PMID- 7864910 TI - Spontaneous uterine rupture during subsequent pregnancy following non-excision of an interstitial ectopic gestation. PMID- 7864911 TI - A scoring error in the Mini-Mental State test. AB - A scoring error is identified in the Mini-Mental and the Modified Mini-Mental State test. The major effect of this error is to produce a gap in the total score distribution of the test, resulting in a potential spurious underestimation of the score. Two possible remedies are suggested to resolve this problem. PMID- 7864912 TI - The value of surveillance cultures on neonatal intensive care units. AB - Nosocomial infections on neonatal intensive care units (NICUs) have been a recognized cause for concern for many years. It is the endeavour of the doctors caring for these children to identify and treat such infections as early as possible in an effort to reduce morbidity and mortality to a minimum. A high percentage of babies on NICU become colonized with Gram-negative bacilli (GNB) with increasing length of stay on the unit. Those babies that remain on NICU for prolonged periods, and who become colonized, tend to be the most premature and sickest infants, and therefore are most at risk of becoming septic. The use of surface cultures in predicting the organisms responsible for sepsis is inefficient and not cost-effective. There is some evidence that endotracheal aspirate cultures in ventilated neonates may be helpful in identifying the pathogens responsible for perinatal pneumonia. Most NICUs have an antibiotic policy for the blind treatment of sepsis which covers the most common organisms responsible, and it is likely that antimicrobial treatment is rarely altered as a result of pathogens isolated from surface cultures. Again this makes the collection of surface cultures a wasteful and costly use of resources. In the light of the increasing incidence of Gram-positive infections on NICUs, antibiotic policies may have to be altered to accommodate these pathogens. As well as continued attention to good infection control measures, it remains with the clinician to be alert to the onset of sepsis in neonates and institute broad spectrum antimicrobial cover after collecting blood and cerebrospinal fluid cultures as indicated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7864913 TI - Reducing smoking. The effect of suggestion during general anaesthesia on postoperative smoking habits. AB - In a double-blind randomised trial, 122 female smokers undergoing elective surgery were allocated to receive one of two prerecorded messages while fully anaesthetised. The active message was designed to encourage them to give up smoking whilst the control message was the same voice counting numbers. No patient could recall hearing the tape. Patients were asked about their postoperative smoking behaviour one month later. Significantly more of those who had received the active tape had stopped or reduced their smoking (p < 0.01). This would suggest a level of preconscious processing of information. PMID- 7864914 TI - Clinical measures in rheumatoid arthritis: which are most useful in assessing patients? AB - OBJECTIVE: To determine the relative accuracy and sensitivity to change of 14 measures commonly used to assess arthritis activity in patients with rheumatoid arthritis (RA). METHODS: Twenty-four patients with RA were prospectively examined every 2 weeks for up to 60 weeks. At each examination, arthritis activity was assessed using 5 physician determined measures (global assessment, swollen joint count, weighted swollen joint count, tender count, weighted tender joint count), 3 patient determined measures (global assessment, pain score, duration of morning stiffness), 3 functional measures (Health Assessment Questionnaire Disability Index, grip strength, 50' walk time), and 3 laboratory measures [Westergren erythrocyte sedimentation rate (ESR), hemoglobin, platelet count]. Accuracy was determined by the degree to which changes in each measure over time were related to changes in other measures (i.e., correlational validity). Sensitivity to change was measured using standardized response means. RESULTS: Over the course of the study, each patient had at least 6 measures change more than 50% from their baseline values. The most highly intercorrelated measures were the physician global assessment (range of partial correlations r = 0.4-0.7), patient global assessment and pain scores (r = 0.2-0.7), the Disability Index (r = 0.3 0.7), and ESR (r = 0.2-0.4). Physician and patient global assessments, pain scores, and the Disability Index were more sensitive to change than other measures, while laboratory measures were generally less sensitive to change. CONCLUSION: Based on the relative accuracy and sensitivity to change of these 14 clinical measures, the physician global assessment, a functional status questionnaire, and the patient global assessment or pain score should be the principal measures used to assess arthritis activity in patients with RA. Recognizing its limitations, the ESR could be included if a laboratory measure is needed. PMID- 7864915 TI - A laboratory model of lumbar disc protrusion. Fissure and fragment. AB - Discs of 20 human lumbar motion segments from donors between 20 and 52 years of age were subjected to a procedure that effected a radial fissure of the anulus, sparing a peripheral layer of approximately 1 mm in thickness. In addition, fragmented tissue pieces that resembled those retrieved at surgery for prolapse were created in the center of the disc. The disc contour was measured under pure axial load as well as in flexion and extension. In the intact specimen, the disc contour shifts in ventral direction in flexion and in dorsal direction in extension. In the 'fissure and fragment' discs a broad-based protrusion develops dorsolaterally at the location of the fissure. The magnitude of the protrusion is independent of flexion or extension angles in the range of +/- 5 degrees. The 'fissure and fragment' discs exhibit disc prolapse at loads between 0.9 and 6.1 kN and flexion angles below 10 degrees, i.e., under loading conditions well in the physiologic range. The findings of this experiment support the hypothesis that disc prolapse--aside from the hyperflexion trauma described in the literature--has to be preceded by generation of radial fissures and tissue fragmentation within the disc. Thus, prolapse appears to be a late event during the course of a long-term degenerative process. PMID- 7864916 TI - A randomized trial of laser vaporization in the management of cervical intraepithelial neoplasia associated with human papilloma virus infection. AB - A randomized controlled trial was carried out at colposcopy clinics in the Birmingham and Midland Hospital for Women, to determine the efficacy of laser vaporization in the management of cervical Human Papilloma Virus (HPV) infection occurring alone or in association with cervical intraepithelial neoplasia (CIN), and to study the natural history of these lesions. The subjects were 365 women referred for investigation of cytological abnormality who were found to have histological evidence of HPV infection alone or in association with CIN1 or CIN2 and were considered suitable for local destructive treatment. The intervention consisted of immediate treatment using a carbon dioxide laser or no treatment. Women in both groups were followed by cytological and colposcopic examinations at intervals of four months. Twelve months after randomization, 25 per cent of women in the non-treatment group had progressed to a more severe degree of histological abnormality compared with 4 per cent in the treatment group (95 per cent confidence interval (CI) for difference in proportion 14-28 per cent). Spontaneous regression of cytological abnormality occurred in 26 per cent (95 per cent CI 19-33 per cent) of untreated women. It is concluded that the short-term efficacy of laser vaporization in the treatment of these lesions has been established. The substantial rate of spontaneous regression suggests, however, that intervention is frequently unnecessary. PMID- 7864917 TI - Quarterly Communicable Disease Review. April to June 1993. From the PHLS Communicable Disease Surveillance Centre. PMID- 7864918 TI - Parental consanguinity as a cause of increased incidence of birth defects in a study of 131,760 consecutive births. AB - The risk for birth defects in the offspring of first cousin parents is substantially higher than in the offspring of non-consanguineous parents. As a general decline in the frequency of consanguineous marriages was observed in this century, one wonders whether consanguinity is still a factor in the appearance of birth defects in developed countries. Based on our registry of congenital anomalies, we think that the answer to this question is "yes." In the population studied in Northeastern France, consanguineous matings were known in 1.08% of the cases with congenital anomalies, vs. 0.28% in controls (P < 0.001). The frequency of the malformations recorded paralleled the degree of consanguinity: out of 38 malformed children, 24 were seen in first cousin matings (10.5 times more frequent than in offspring of nonconsanguineous couples), 8 in second cousin marriages, and 6 in more distantly consanguineous matings. Consanguineous mothers were more often pregnant than nonconsanguineous mothers (P < 0.01) and they had more stillbirths than nonconsanguineous mothers. These results must be taken into account when counseling consanguineous couples. PMID- 7864919 TI - The Baxter PCA system: balloon rupture. PMID- 7864920 TI - State report. Will employer mandates really work? Another look at Hawaii. PMID- 7864921 TI - Increased maternal serum free beta-human chorionic gonadotrophin concentrations in Down's pregnancies: an artefactual finding? PMID- 7864922 TI - Properties of the fluorescent sodium indicator "SBFI" in rat and rabbit cardiac myocytes. AB - INTRODUCTION: Although some properties of the fluorescent sodium indicator "SBFI" are known, there is no accepted method by which the SBFI signal might be calibrated for intracellular Na (Nai) in cardiac cells. The first aim of this study was to characterize the loading and compartmentalization of this indicator in single cardiac myocytes. The second aim was, from experimental observation, to develop a rational calibration method for SBFI. The third aim was to use this Na indicator to study the dependence of tonic contraction on Nai in voltage-clamped ventricular myocytes. METHODS AND RESULTS: SBFI was incorporated into myocytes by incubating with the acetoxymethyl ester (10 microM) for 2 hours. This led to an intracellular concentration of SBFI free acid of 122 +/- 17 microM. We considered a number of issues with respect to compartmentalization of indicator and, under our conditions, we found the majority (71%) of indicator was situated in the cytoplasm. Therefore, SBFI indicates mainly changes of cytoplasmic Na. Calibration of the indicator for Nai was performed by equilibrating internal and external Na. We investigated the conditions required for optimum transmembrane Na equilibration and found it necessary to use a calibration solution free of both Ca and magnesium (Mg). The Na ionophores gramicidin D and monensin were both required, and it was also necessary to inhibit the Na/K pump for optimum Na equilibration. Using these conditions, the Nai concentration in quiescent rat ventricular myocytes was 10.9 +/- 0.74 mM (mean +/- SEM, n = 40; equivalent to an Na activity of 8.3 mM). The concentration of Nai was significantly lower in quiescent rabbit myocytes: 3.8 +/- 0.23 mM (n = 24; equivalent to an Na activity of 2.9 mM). In voltage-clamped rabbit myocytes, inhibition of the Na/K pump caused a rise of Nai; there were also marked effects on the tonic shortening elicited by ramp depolarizations. As Nai rose, the magnitude of tonic shortening increased and its voltage dependence also changed. CONCLUSION: These results confirm the suitability of SBFI for measuring Nai in cardiac cells. Provided that steps are taken to optimize transmembrane Na equilibration, the indicator can be calibrated for Nai. The different Nai of rat and rabbit myocytes has implications for the function of sarcolemmal Na/Ca exchange in each cell type. An Nai of 10.9 mM in rat myocytes gives a calculated reversal potential for the exchange of -35 mV. In comparison, an Nai of 3.8 mM in rabbit myocytes leads to a reversal potential for the exchange +45 mV. Therefore, relatively small changes of Nai can shift the reversal potential of the exchange to values that are substantially more positive or negative than zero. The behavior of voltage-dependent tonic contraction in rabbit myocytes was consistent with the Na/Ca exchange reversal potential being more positive than zero in these cells. PMID- 7864923 TI - Comparative study of infectious complications of different types of chronic central venous access devices. AB - BACKGROUND: Various devices for central venous access are widely used in patients with cancer. The authors studied the incidence of infectious complications affecting these different devices. METHODS: A retrospective study of 111 central venous access devices (VAD) placed in 1992 was conducted. RESULTS: Subcutaneous ports were placed in 42 patients, single lumen Groshong catheters in 45, single lumen Hickman catheters in 15, double lumen Hickman catheters in 5, and double lumen Groshong catheters in 4. Prognostic factors analysis was performed with the log rank test and Cox's multivariate analysis. Different VAD types were compared with the likelihood ratio test. There was no significant difference in the risk of VAD-related infection between Hickman and Groshong catheters. Double lumen catheters were slightly more likely to cause infectious complications than single lumen catheters, although the difference was not statistically significant (P = 0.072 and 0.083 for bacteremia and site infection, respectively). No significant difference was observed in the risk of infection between subcutaneous ports and external catheters. Multivariate analysis using Cox's proportional hazards model demonstrated age younger than 50 years as the only significant risk factor, thus younger patients should be monitored more closely. CONCLUSIONS: No significant difference was observed in the risk of infection between subcutaneous ports and external catheters. There was a slightly higher risk of infection in double lumen catheters than single lumen catheters, although the difference did not reach statistical significance. Considering the small sample size, the results should be confirmed in larger prospective studies. PMID- 7864924 TI - Epidemiology of celiac sprue: a community-based study. AB - OBJECTIVE: To address the frequency and outcome of celiac disease in a United States community. METHODS: We identified all Olmsted County, Minnesota, residents diagnosed with this condition during the period, 1960 through 1990, using the resources of the Rochester Epidemiology Project. Twenty-eight incident cases (19 women, nine men) were identified. RESULTS: The overall age- and gender-adjusted incidence of celiac disease in the community was 1.2 per 100,000 person-yr (95% CI 0.7, 1.6). There were no significant changes in incidence over time, although rates did increase; the incidence was similar in men and women and rose with age in both genders (p < 0.05). Survival in this inception cohort was 100% at 6 months and 96% at 5 yr, which was not significantly different from expected. The estimated prevalence on January 1, 1991, was 21.8 per 100,000. CONCLUSION: This study provides the first epidemiologic data on celiac disease in the United States. PMID- 7864925 TI - Melanoma, melanocytic nevi, and other melanoma risk factors in children. PMID- 7864926 TI - Puncture of the laryngeal mask airway cuff. PMID- 7864927 TI - Electrocardiographic and echocardiographic changes associated with malignant catatonia. AB - We describe a case of malignant catatonia manifested by catatonic symptoms, fever, hemodynamic instability, and acute neurologic decline that was associated with electrocardiographic and echocardiographic abnormalities similar to those noted in patients with other central nervous system processes. The patient's electrocardiographic and echocardiographic abnormalities resolved after successful electroconvulsive therapy for the underlying neuropsychiatric disorder. The theoretic, physiologic, and clinical significances of this case are discussed. PMID- 7864928 TI - Bronchospasm and the laryngeal mask airway. PMID- 7864929 TI - Tobacco and drug use. PMID- 7864930 TI - Human immunodeficiency virus type 1 and type 2 seroprevalence in cornea donors. AB - Routine screening of cornea donors for human immunodeficiency virus type 1 (HIV 1) has been established and has reduced the risk of HIV-1 transmission to a minimum. Screening for HIV-2 is less common. We evaluated 100 cornea donors for HIV-2 and 166 cornea donors for HIV-1 according to our routine screening procedure. Enzyme-linked immunosorbent assays (ELISAs) with high sensitivity were used to detect antibodies in donor blood. HIV-2 seroconversion was not found in any of the 100 cases tested, whereas HIV-1 seroconversion was detected in 4 of 166 cases; consecutive Western-blot analysis showed only 1 positive result. Thus, 1 of 166 cases (0.6%) had to be considered infected with HIV-1. Our findings of HIV-1 seroprevalence are comparable with those obtained in studies carried out in Europe and the United States. Data are lacking for comparison with our results concerning HIV-2 seroprevalence. Because of the epidemiologic situation of HIV-2 in Europe, different seroprevalence rates would be expected. Routine screening of potential cornea donors for HIV-2 in Germany may be necessary only if the seroprevalence rises in the population. PMID- 7864931 TI - The risks of ignoring insurance risk management. AB - Health insurers face financial risks when they assume liability for the difference between difference between premium revenues and their estimates of future claims costs for a group. Market reform proposals vastly increase the amount of risk health plans of all types will face. A case study is used to show how insurers bidding in an alliance environment must either commit contingency reserves to cover these risks, increase premiums to reduce them, or forgo the business. Unless legislation includes measures that reduce these risks or enable health plans to carry them, premiums are likely to increase greatly. PMID- 7864932 TI - Acute promyelocytic leukemia with t(15;17) abnormality after chemotherapy containing etoposide for Langerhans' cell histiocytosis. PMID- 7864933 TI - Women in medicine--socialization, stereotypes and self perceptions. AB - Eleven women in various specialities, including the academic and administrative spheres, were interviewed with regard to their experiences throughout their career. These women all held senior positions in Medicine and represent a broad age range (35-69 years). Information gathered during the interviews was analysed thematically in an attempt to develop a basis for further research examining predictors of success for women in medicine. PMID- 7864934 TI - Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS) AB - It has yet to be established whether substantial reduction of plasma lipids will lead to retardation, and to what extent and how quickly, of diffuse and focal coronary atheroma. The Multicentre Anti-Atheroma Study (MAAS) is a randomised double-blind clinical trial of 381 patients with coronary heart disease assigned to treatment with diet and either simvastatin 20 mg daily or placebo for 4 years. Patients on simvastatin had a 23% reduction in serum cholesterol, a 31% reduction in low-density lipoprotein cholesterol, and a 9% increase in high-density lipoprotein cholesterol compared with placebo over 4 years. Quantitative coronary angiography was done at baseline, and after 2 and 4 years. 167 patients (89%) on placebo and 178 (92%) on simvastatin had baseline and follow-up angiograms. In the placebo group there were reductions in mean lumen diameter (-0.08 mm) and in minimum lumen diameter (-0.13 mm). Treatment effects were +0.06 (95% CI 0.02 to 0.10) and +0.08 mm (0.03 to 0.14) for mean and minimum lumen diameter, respectively (combined p = 0.006). Patients on placebo had an increase in mean diameter stenosis of 3.6% and the treatment effect of simvastatin was -2.6% (-4.4 to -0.8). Treatment effects were observed regardless of diameter stenosis at baseline. On a per-patient basis, angiographic progression occurred less often in the simvastatin group, 41 versus 54 patients; and regression was more frequent, 33 versus 20 patients (combined p = 0.02). Significantly more new lesions and new total occlusions developed in the placebo group, 48 versus 28, and 18 versus 8, respectively. There was no difference in clinical outcome. The numbers of patients who died or had a myocardial infarction were 16 and 14 in the placebo and simvastatin groups, respectively. In the placebo group more patients underwent coronary angioplasty or re-vascularisation, 34 versus 23 on simvastatin. The trial showed that 20 mg simvastatin daily over 4 years reduces hyperlipidaemia and slows progression of diffuse and focal coronary atherosclerosis. PMID- 7864935 TI - Substance abuse treatment. Beyond the Minnesota model. PMID- 7864936 TI - Imprinting: a gamete's point of view. AB - The recent isolation of imprinted mammalian genes has at last allowed the analysis of the molecular controls that regulate monoparental gene expression. Remarkably, many expectations as to how the imprinting mechanism works have been confounded by these studies. As a result, the time now seems right to reconsider our current understanding of the nature of imprinting, and how best it can be defined. Here, I discuss the past and present understanding of imprinting in the light of results obtained from studies of endogenous imprinted genes, and finally propose that the current multiplicity of imprinting terms and definitions be replaced by a single term and definition. PMID- 7864937 TI - Genetics of diabetes mellitus. PMID- 7864938 TI - Taming the Medicaid beast. Lawmakers are looking to managed care to rein in escalating costs. PMID- 7864939 TI - Repair and transcription. Collision or collusion? AB - While some proteins have distinct responsibilities in both transcription and DNA repair, additional proteins are needed to couple these essential DNA transactions in expressed genes. PMID- 7864940 TI - Motion perception. Moving on the surface. AB - Recent studies of motion perception show that, in the brain's internal representation of three-dimensional space, distances may be less important than relationships to surfaces. PMID- 7864941 TI - Plant self-incompatibility. The key to specificity. AB - Experiments with transgenic plants provide strong evidence that the locus controlling the female side of recognition in self-incompatibility has been correctly identified, and supoort the view that a ribonuclease is involved. PMID- 7864942 TI - Time to stand up for abortion providers. PMID- 7864943 TI - Nicotine-sensitive myasthenia gravis. PMID- 7864944 TI - Intravenous iron therapy for severe anaemia in systemic-onset juvenile chronic arthritis. AB - The role of iron supplementation in treating the anaemia of systemic-onset juvenile chronic arthritis is not clear. Eight affected children with severe persistent anaemia unresponsive to oral iron therapy were treated with intravenous iron saccharate. From a median post-oral-iron value of 8.0 g/dL (range 6.5-9.5), haemoglobin rose to 11.0 g/dL (10.1-12.1) (p = 0.01). The concentration of serum transferrin receptor, an indicator of iron deficiency, before intravenous therapy correlated with the increase in haemoglobin (r = 0.88, p < 0.01). Intravenous iron saccharate could be an effective treatment for chronic anaemia in this condition, especially with iron deficiency not responsive to oral iron. PMID- 7864945 TI - Modified test for activated protein C resistance. PMID- 7864946 TI - Plague epidemic. Bottleneck keeps existing vaccine off the market. PMID- 7864947 TI - Thoracic aortic aneurysm and rupture in giant cell arteritis. A descriptive study of 41 cases. AB - OBJECTIVE: To determine the features and outcomes of patients with giant cell arteritis (GCA) who have aneurysms or rupture of the thoracic aorta. METHODS: Patients with GCA seen over a 40-year period who had aneurysms and/or rupture of the thoracic aorta were identified by assistance of a computerized indexing system. The presence of thoracic aortic aneurysms (TAA), with or without aortic valve insufficiency (AI), was determined by radiographs, computed tomography scans, and ultrasound studies of the thorax, angiograms of the aorta, and postmortem examination. RESULTS: Ten men and 31 women with GCA were found to have TAA and/or rupture. Three developed TAA before GCA was diagnosed, 5 developed aortic findings near the time of the diagnosis, and 33 after the diagnosis of GCA (median of 7 years after diagnosis). Sixteen patients developed acute aortic dissection, which caused death in 8. Nineteen patients also had AI due to aortic root dilation, 15 of whom developed congestive heart failure. Eighteen patients underwent 21 surgical procedures for TAA resection and/or aortic valve replacement or repair. Aortitis was documented histologically in 10 cases. CONCLUSION: Thoracic aortic complications in GCA are associated with serious outcomes that have been underrecognized and may be fatal. Physicians should be alert to the development of these complications at any time in the course of GCA, even many years after usual symptoms have subsided. PMID- 7864948 TI - Panic disorder. An overlapping or independent entity? AB - We compared three groups of patients with panic disorder, generalised anxiety disorder and major depressive episode with a control group. Methods of comparison included a clinical profile of the patients, assessed by the Arabic version of the Present State Examination (PSE), a psychological battery of tests measuring personality traits and depressive and anxiety states, and the dexamethasone suppression test (DST) as a biological marker. Our data showed that psychological assessment and DST did not significantly differentiate between the three disorders. Despite a symptom overlap between the disorders, however, some symptoms were associated significantly more often with one disorder than another. Patients with panic disorder differed from patients with major depressive episode in showing more situational, avoidance and free floating anxiety, and more anxious foreboding. They showed less self-negligence, ideas of guilt, early awakening and social withdrawal. Compared with patients with generalised anxiety disorder, patients with panic disorder showed more loss of interest and muscle tension and less anxious foreboding, restlessness, inefficient thinking, social withdrawal and delayed sleep. Our conclusion is that the clinical course and the symptom profile of panic disorder justifies its existence as an independent diagnostic category. PMID- 7864949 TI - Albuterol delivered by metered-dose inhaler to treat acute bronchitis. AB - BACKGROUND: Previous research has suggested that cough associated with acute bronchitis is more likely to subside within 7 days when treated with albuterol than with an antibiotic. This study examines the effectiveness of aerosolized albuterol for the treatment of acute bronchitis in patients treated with erythromycin or placebo. METHODS: A double-blind, randomized placebo-controlled trial of albuterol delivered by metered-dose inhaler (MDI) was conducted in a primary care setting with healthy adult patients who presented with a productive cough of fewer than 30 days' duration. In addition to randomization for albuterol, patients were also randomized to receive erythromycin or placebo. Outcomes were assessed at follow-up after 7 days. RESULTS: Patients treated with albuterol MDI were less likely to be coughing after 7 days of treatment than were patients using a placebo inhaler (61% still coughing vs 91%, P = .02). When analysis was stratified by cigarette smoking status and the use of erythromycin, the differences observed between albuterol MDI patients and controls persisted. CONCLUSIONS: Albuterol appears to reduce the likelihood that patients with acute bronchitis will be coughing after 7 days following initiation of treatment. This effect appears to be independent of cigarette smoking or the concomitant use of antibiotics. PMID- 7864950 TI - Evaluation of two enzyme-linked immunosorbent assays for the diagnosis of canine atopy. AB - Serum samples from 10 dogs without skin disease, 10 with non-atopic pruritic skin disease, and 10 atopic dogs were tested blind by using two enzyme-linked immunosorbent assays (ELISAS) (Veterinary Allergy Test Kit; All-Vet [test A] and Elisarest; Bloxham Laboratories [test B]) designed to detect immunoglobulin E antibodies to environmental allergens. All the dogs tested had at least three positive reactions when using test A, and 28 of the dogs had at least one positive reaction when using test B. The median numbers of positive reactions observed in the three groups of dogs were not significantly different for each test. Significantly more reactions were observed with test A in each group (P < 0.001) than with test B. The sensitivity of both the tests was 100 per cent, but the specificity of test A was 0 per cent and the specificity of test B was 10 per cent. The positive predictive values of tests A and B were 33.3 per cent and 35.7 per cent, respectively, and the negative predictive values were 0 and 100 per cent. The poor specificities and low positive predictive values indicate that the positive results obtained when using these ELISAS are of no diagnostic value in canine atopy. PMID- 7864951 TI - The future provision of a specialist oral surgery and orthodontic services. PMID- 7864952 TI - Shoreline nails or multiple Beau's lines? PMID- 7864953 TI - Cohabitation and pregnancy-induced hypertension. PMID- 7864954 TI - Placebos in medicine. PMID- 7864955 TI - Pregnancy and prosthetic heart valves. PMID- 7864957 TI - Accepting patients' gifts. PMID- 7864956 TI - Multiple cases of Dandy-Walker malformation in three sheep flocks. PMID- 7864958 TI - Cervicothoracic vertebral subluxation causing ataxia in sheep. PMID- 7864959 TI - Palatal inlays. PMID- 7864960 TI - Prognostic significance of auer rods in myelodysplasia. PMID- 7864961 TI - Criteria for the diagnosis of infective endocarditis. PMID- 7864962 TI - Respiratory distress syndrome. PMID- 7864963 TI - Oral pamidronate in refractory Paget's disease. PMID- 7864964 TI - Re: Housing for people with mental illnesses. PMID- 7864965 TI - Health care reform in California. PMID- 7864966 TI - Advantages of risk sharing. PMID- 7864967 TI - Efficacy of newer antidepressants. PMID- 7864968 TI - Megestrol acetate for the prevention of hot flashes. PMID- 7864969 TI - Population control not the answer. PMID- 7864970 TI - Mozart's subdural hematoma. PMID- 7864971 TI - Depression and the later development of cancer. PMID- 7864972 TI - Subdural hematoma and CT of the paranasal sinuses: a radiologic error? PMID- 7864973 TI - Fasciitis and fasciitis-panniculitis in chronic graft-versus-host disease. PMID- 7864974 TI - Estrogens and cataract. PMID- 7864975 TI - The historical method in psychiatric research. PMID- 7864976 TI - Child sexual abuse--looking in the wrong direction? PMID- 7864977 TI - Strength of the genetic effect in schizophrenia. PMID- 7864978 TI - Cost-effectiveness of antidepressants. PMID- 7864979 TI - Medicine and health care: marital status uncertain. PMID- 7864980 TI - Effects of combined supplementation with antioxidants on low-density lipoprotein oxidation. PMID- 7864981 TI - Effects of dietary iron intake on stored iron, free iron, and coronary disease. PMID- 7864982 TI - A fatal case of acute renal failure associated with non-fulminant hepatitis A. PMID- 7864983 TI - Excretion of radiopharmaceuticals into breast milk. PMID- 7864984 TI - Is white coat hypertension innocent? PMID- 7864985 TI - Comments on "Patterns of failure following loco-regional radiotherapy in the treatment of limited stage small cell lung cancer". PMID- 7864986 TI - Vitamin A for varicella. PMID- 7864987 TI - Transmission of human granulocytic ehrlichiosis. PMID- 7864988 TI - Dangers of bismuth iodoform paraffin paste. PMID- 7864989 TI - Modified APC resistance assay for patients on oral anticoagulants. PMID- 7864990 TI - Scandinavian simvastatin study (4S) PMID- 7864991 TI - HLA and hepatitis B infection. PMID- 7864992 TI - The Culyer report. PMID- 7864993 TI - Malaria vaccine research. AB - In our report "Activation of Raf as a result of recruitment to the plasma membrane" (3 June, p. 1463) (1), panels E and F of figure 1 on page 1464 were incorrect. The correct photographs appear below. In addition, the [See figure in the PDF file] second sentence of the legend to figure 1 should have read, "The Raf constructs were tagged at the COOH-terminus with a Glu-Glu epitope (MEYMPME) (24) for c-Raf, or at the NH(2)-terminus with both the Glu-Glu and the Myc (MEQKLISEEDL) (23) epitopes for RafCAAX"; the next-to-the-last sentence of the legend to figure 1 should have read, "The c-Raf constructs in (A through D) are Glu-Glu-tagged and were detected by using an anti Glu-Glu antibody, and the RafCAAX and Raf6QCAAX constructs used in E and F were detected by using the antibody to Raf COOH-terminal peptide"; and the third sentence of note 26 should have read, "After blocking with 5% milk in phosphate-buffered saline (M-PBS), cells were incubated with a mouse monoclonal antibody to Glu-Glu or a rabbit polyclonal antibody to a 20-amino acid COOH-terminal peptide of Raf-1 (Santa Cruz Biotechnology, Santa Cruz, California), washed, and incubated with donkey antibodies to mouse or rabbit IgG combined with Texas Red (Jackson) in M-PBS, washed, and mounted in FITC-Guard (Testog)." PMID- 7864994 TI - Salivary duct cannulation facilitates interventional procedures. PMID- 7864995 TI - Falsification of a single-species hypothesis by using the coefficient of variation: a critique. PMID- 7864996 TI - Treatment of basal cell carcinoma with intralesional interferon. PMID- 7864997 TI - Reliability of notification data for childhood bacterial meningitis. PMID- 7864998 TI - Parasacral approach for sciatic nerve block. PMID- 7864999 TI - Neonatal platelet reactivity and serum thromboxane B2 production in whole blood: the effect of maternal low dose aspirin and platelet activation in normotensive and hypertensive pregnancies complicated by intrauterine growth retardation. PMID- 7865000 TI - Angiotensin converting enzyme a new tool for the follow-up of endothelial injury in paediatric vasculitides. PMID- 7865001 TI - Oxygen consumption after cardiopulmonary bypass--different measuring methods yield different results. PMID- 7865002 TI - Phase II window therapy. PMID- 7865003 TI - Taking a shot at the editor. PMID- 7865004 TI - Standardized regression coefficients and relative importance of pain and functional disability to patients with rheumatoid arthritis. PMID- 7865005 TI - Forecasting physician workforce requirements. PMID- 7865006 TI - Safety and transcervical endometrial resection. PMID- 7865007 TI - Nicotine-sensitive myasthenia gravis. PMID- 7865008 TI - Fitness to drive in the elderly. PMID- 7865009 TI - Antibodies to HTLV-I in Sjogren's syndrome. PMID- 7865010 TI - The gap between marketplace technology and hospital computing systems. PMID- 7865011 TI - Hemorrhage and shock associated with invasive pneumococcal infection in healthy infants and children--New Mexico, 1993-1994. AB - From December 1993 through May 1994, four previously healthy children (including two infants) in New Mexico developed a severe illness characterized by septic shock and hemorrhage into the skin or internal organs. An investigation subsequently implicated Streptococcus pneumoniae as the cause of illness. The two infants attended the same child care center (CCC) and died 6 weeks apart. This report describes the syndrome, an investigation of potential transmission in the CCC, and prevention measures. PMID- 7865012 TI - Theophylline, erythropoietin, haematocrit and hepatitis B. PMID- 7865013 TI - Possible improvement in uteroplacental blood flow during atrial natriuretic peptide infusion in preeclampsia. PMID- 7865014 TI - Abuse history and chronic pain in women: I. Prevalences of sexual abuse and physical abuse. PMID- 7865015 TI - Use of ELISAs in the diagnosis of canine atopy. PMID- 7865016 TI - Dantrolene and thyroid crisis. PMID- 7865017 TI - Dental and facial asymmetries. PMID- 7865018 TI - The scientific method. PMID- 7865019 TI - [Factors affecting the results of in vitro fertilization--I. The effect of age]. AB - Age is a major factor affecting the results of IVF and ET. We studied the results of 697 couples treated in our programme of in vitro fertilisation and embryotransfer. We demonstrated increasing numbers of cancelled cycles in older women--the cancellation rate was 17.7% in patients under thirty and 50% in women 38-40 years old. The cut-off line of effectivity is the age of 36-37 years. In women aged 38 and older we demonstrated a decrease of pregnancy rate per transfer from 25.5% to 14-16%. However, there was no higher pregnancy loss in older women in our series. PMID- 7865020 TI - Management of acute myocardial infarction. PMID- 7865021 TI - Delayed diagnosis of biliary leak due to bile duct division during cholecystectomy. PMID- 7865022 TI - Epidural block for postpartum sterilisation. PMID- 7865023 TI - Diagnostic importance of urothelial cells of the dog and cat. AB - The cells lining the canine and feline urinary tract and their role in the diagnosis of urological diseases in small animals is assessed. The urothelium was found to consist of transitional epithelial cells ranging from the calyces to the urethra. Caudate cells were found lining the ureter, renal pelvis and the calyces. There was no feature that could be used to distinguish the transitional cells from different parts of the urothelium. Squamous cells were found lining the urinary tract from the trigone to the vagina in females and to the urethra in male animals. Hydropic degeneration in the form of vacuolation of the cytoplasm, granulation and total loss of cytoplasm was one of the urine-induced degenerative changes recorded in the transitional cells. The significance of the degenerative changes in the management of urological problems is discussed. PMID- 7865024 TI - Insect segmentation. A glance posterior. AB - Segmentation gene expression patterns can be radically different in some short germ and long-germ insects, but other types of short/intermediate-germ insects may use Drosophila-like segmentation mechanisms. PMID- 7865025 TI - T-cell co-receptors. The end of a frustrating search. AB - The identification of a 'silencer' element that turns off CD4 gene expression at specific states in thymocyte differentiation may help to resolve an important outstanding problem in immunology. PMID- 7865026 TI - Potassium channels. New channel subunits are a turn-off. AB - Recent discoveries indicate that potassium channel beta subunits can have profound functional roles, particularly in determining the channel inactivation properties. PMID- 7865027 TI - [Residual anophelism in Italy: distribution in 4 southern regions]. AB - About 40 years after malaria eradication from Italy, the potential vectors of this disease, Anopheles labranchiae, Anopheles superpictus and Anopheles sacharovi, are still present in some regions of the South. Since 1991 the Laboratory of Parasitology, Istituto Superiore di Sanita, in collaboration with the Local Health Authorities, carried out an investigation to assess the levels of these potential anopheline vectors in Calabria, Puglia, Sicily and Sardinia. A. labranchiae, the most important vector, was found in all the regions visited, where is probably present in scattered foci all over the territory. The most common breeding sites were represented by rivers and streams, followed by ponds and ground pools. The larval densities varied greatly from 0.01 to 33 larvae/dip; likewise the adult densities, recorded in animal shelters, varied from < 10 to > 1000 female/shelter. The higher adult densities were recorded in Calabria, along the West coast. The other important vector in Southern Italy, A. superpictus, was found both in the West and East coasts of the same region, showing low larval and adult densities. Anopheles sacharovi, that was an important malaria vector in Puglia and Sardinia, was not found. Four populations of A. labranchiae were tested to determine the susceptibility to some insecticides. All of these populations were fully susceptible to deltamethrin, malathion and DDT, while showed a reduced susceptibility to permethrin and propoxur. PMID- 7865028 TI - European Respiratory Society Annual Congress. Nice, France, October 1-5, 1994. Abstracts. PMID- 7865029 TI - A piperidine amino acid, 2,4,5-piperidinetricarboxylic acid from Clitocybe acromelalga. AB - A new piperidine amino acid, 2,4,5-piperidinetricarboxylic acid (11) was isolated from the poisonous mushroom, Clitocybe acromelalga. The structure determination and its biogenetic potential are discussed. PMID- 7865030 TI - Product autofluorescence activation in the cytochrome P450 monooxygenase system. AB - The relative increase of the 7-ethoxycoumarin-O-deethylase and the 6,7 dimethoxycoumarin-O-demethylase activities were found 93 and 236% using a reconstituted cytochrome P4502B1:NADPH-P450 reductase system by adding to the reaction mixtures their own products. The assays were irradiated during the reactions with the excitation wavelength maximum of their products umbelliferone (lambda E = 365 nm) or scopoletin (lambda E 98 nm), respectively. Addition of the products to the reaction mixtures without irradiation (dark reaction) had no activating effect on the specific activities of the 7-ethoxycoumarin-O-deethylase or the 6,7-dimethoxycoumarin-O-demethylase. The relative increase of the specific activities is dependent on the excitation light intensities and was at maximum when the light intensity at the sample cuvette was 0.4 mW/cm2. The activation energies of the P4502B1-dependent 7-ethoxycoumarin-O-deethylation reaction obtained from Arrhenius plots with and without added umbelliferone and irradiation with lambda E = 365 nm are 14.7 kJ/mol and 33.5 kJ/mol, respectively, in the temperature range of 27-37 degrees C. The irradiation energy of the fluorescent product umbelliferone change the catalytic mechanism, which has a two times lower activation energy in the presence of the irradiated product umbelliferone. Umbelliferone and scopoletin have highest fluorescence intensities in the wavelength range of the blue light (440-480 nm). The photochemical action spectrum of the 7-ethoxycoumarin-O-deethylase of the P4502B1:reductase system is also found to be in the wavelength range of 420-470 nm. No activation effect was seen with irradiating light lower than 400 nm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865031 TI - A novel halogenated compound possessing antibiotic and cytotoxic activities isolated from the fungus Resinicium pinicola (J. Erikss.) Erikss. & Hjortst. AB - Pinicoloform, a novel unbranched acyclic compound containing a trichloromethyl group, has been isolated from extracts of the mycelia of the Basidiomycete Resinicium pinicola. It was isolated because of its ability to induce morphological and physiological differentiation of mammalian cells, although it also exhibits antibiotic and cytotoxic activities. The structure of pinicoloform was determined by spectroscopic methods. PMID- 7865032 TI - On the expression of several Lhc genes in garden cress (Lepidium sativum L.). AB - The polymerase chain reaction was used to prepare gene-specific probes for several Lhc genes coding for chlorophyll a/b-binding proteins of cress (Lepidium sativum L.). Due to the presence of about 150 basepairs of the coding region, the isolated clones could be attributed to Lhc a3 (1 clone), Lhc b1 (5 clones), Lhc b2 (1 clone) and Lhc b3 (1 clone) genes. Probes prepared from the 3'non-coding regions of the clones did not cross-hybridize; they were specific for 3 different Lhc b1 transcripts and one each of Lhc b2, Lhc b3 and Lhc a3 transcripts. The transcript levels were higher in leaves than in cotyledons of light-grown seedlings; they decreased significantly in cotyledons from week 1 to week 4. The levels of 2 Lhc b1 transcripts (detected with probes cd1 and cd2) changed from 1 week old cotyledons (30% cd1, 28% cd2) to 3 months old leaves (14% cd1), 44% cd2), stems (11% cd1, 56% cd2) and fruits (15% cd1, 62% cd2, all values percent of total transcripts), whereas transcript levels of another Lhc b1 gene (detected with probe cd3) and of a Lhc a3 gene remained nearly constant. The level of Lhc b2 and Lhc b3 transcripts were 1-2 orders of magnitude smaller than those of the other Lhc transcripts. The data obtained with cress plants are compared with published data from other plants. PMID- 7865033 TI - Antioxidative effect of extracts from Erodium cicutarium L. AB - Extracts from Erodium cicutarium L. (EC) and some standard substances present in EC extracts were tested for their antioxidative properties during Fe(2+)-induced triglyceride oxidation. Hydrophobic fractions such as petroleum ether (PEE), benzene (BE) and chloroform I (ChE I) extracts as well as hydrophilic fractions i.e. water (WE) and ethyl acetate (EAE) showed an antioxidative effect. Among the tested substances vitamin C and some polyphenolic compounds: tannin, (+)-catechin and gallic acid exhibited antioxidative activity, stronger than the one of the mentioned extracts. PMID- 7865034 TI - The Medical Council of Canada's key features project: a more valid written examination of clinical decision-making skills. AB - In 1986 the Medical Council of Canada (MCC) commissioned a six-year research and development project to create a new, more valid written examination of clinical decision-making skills for the Canadian Qualifying Examination in Medicine. At that time, the qualifying examination consisted of three booklets of multiple choice questions and one booklet of patient management problems administered over a two-day period. All graduates of Canadian and foreign medical schools must pass this examination before practicing medicine anywhere in Canada except Quebec. The project was undertaken because (1) numerous studies do not support the use of patient management problems (PMPs) to assess clinical decision-making skills, and (2) research results on the characteristics of clinical decision-making skills offered guidance to develop new approaches to their assessment. In particular, research suggested that these skills are specific to the case or problem encountered and are contingent on the effective manipulation of a few elements of the problem that are crucial to its successful resolution--the problem's key features. The problems developed by this project focused only on the assessment of these key features. The project was implemented in three overlapping phases over a six-year period, 1986-1992, each containing a development component followed by a pilot test through which the research studies were carried out. The pilot tests were conducted by presenting sets of new key feature problems to classes of graduating students in medical schools across Canada.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865035 TI - Are the teachers teaching? Measuring the educational activities of clinical faculty. AB - As the teaching activities of medical school faculty are given greater emphasis, medical schools must find a way to recognize and reward excellence in teaching. In order to properly evaluate teaching, the authors developed an instrument for measuring the various teaching activities of their faculty. The Relative Value Scale in Teaching weights all teaching activities according to labor intensity, preparation time, level of responsibility, and educational value. The scale quantifies levels of teaching and allows comparison among diverse teaching activities. This complements qualitative measures of teaching and can enhance participation in educational programs as well as recognition of educators. PMID- 7865036 TI - Medunsa and the training of black doctors for South Africa. AB - Medunsa, the Medical University of Southern Africa, was founded in 1976 to address both the under-representation of blacks in the health professions and the lack of good health care in the homelands. The university trains most of the black physicians, dentists, veterinarians, and allied health professionals in South Africa, and it places a great emphasis on community service and preventive medicine. Medunsa also has programs to help socially and academically disadvantaged applicants. In some respects, the ongoing development of Medunsa mirrors that of historically black health professions schools in the United States, and Medunsa struggles with some of the same problems. Medunsa can learn from the histories of these American schools as it faces the challenges of the post-apartheid era; in turn, all U.S. schools can learn from Medunsa's history as they struggle with physician supply questions and health care reform issues. PMID- 7865037 TI - A decade of physician payment reform. PMID- 7865038 TI - Flexner Award. Richard S. Ross, MD. PMID- 7865039 TI - Baxter Award. Francis S. Collins, MD, PhD. PMID- 7865040 TI - Community hospital and medical school cooperation in continuing medical education. AB - PURPOSE: To determine the extent and trends of cooperation in continuing medical education (CME) between community teaching hospitals and medical schools in the United States. METHOD: A questionnaire was sent in September 1992 to the directors of CME at 276 teaching hospital members of the Association for Hospital Medical Education (AHME). The survey was designed to answer two questions: (1) What is the extent of cooperation between hospital CME providers and medical schools? (2) In the next three years will community hospitals seek competitive or collaborative relationships in CME with medical schools? RESULTS: By late April 1993, 216 (78%) of the questionnaires had been returned. Of these, 177 (64% of the sample) were analyzed. Of the responding hospitals, 91 (52%) cooperated with 92 medical schools in CME; 75 (45%) of the hospitals planned to increase cooperation. Only ten (11%) of the hospitals described their current CME relationship with a medical school as "competitive in most areas"; 23 (14%) expected to increase competition in the next three years. Forty-one (24%) of the respondents were part of a community hospital CME consortium; only 20 (16%) of the other institutions expected to participate in a consortium in the next three years. Hospital size and membership in the Association of American Medical Colleges' Council of Teaching Hospitals were generally correlated with current and future competition in CME with a medical school and likely participation in a community CME consortium. CONCLUSION: The majority of teaching hospital members of the AHME perceived that they would have cooperative relationships in CME with affiliated medical schools in the three years following the survey. These collaborative relationships should provide an important basis for the further planning and development of medical education consortia. PMID- 7865041 TI - The effect of a required third-year family medicine clerkship on medical students' attitudes: value indoctrination and value clarification. AB - BACKGROUND: The effect of a required six-week third-year family medicine clerkship was examined within a framework of professional socialization. Socialization was considered to consist of an institutional process, i.e., value indoctrination, and a learner process, i.e., value clarification. METHOD: Pre- and postclerkship data from 1,095 students (classes of 1981-1993) at the University of Arizona College of Medicine were analyzed. In addition, specialty match data were obtained. Factor analysis of 19 items on the pre- and postclerkship questionnaires was used to derive four scales measuring attitudes related to family medicine. The students were first grouped into four groups: those who preferred family medicine before and after the clerkship, those who preferred other specialties both times, those who switched to family medicine, and those who switched away from family medicine. Then the students were grouped into eight groups by dividing each of the specialty-preference groups into two sections: those who matched to family medicine and those who did not. Statistical comparisons involved the use of the t and F statistics. RESULTS: Usable data were available for a maximum of 997 students (91%). The students' attitudes about family medicine changed during the clerkship to become more consistent with their postclerkship specialty preferences. In addition, more students preferred family medicine after the clerkship than before it. When each group was further divided into those matching and not matching into family medicine, no significant difference in attitudes was found between those matching and those not matching. CONCLUSION: These results reflect both a value clarification process and a value indoctrination effect. The discrepancy between postclerkship specialty preferences and later match data indicates that the indoctrination effect and clarification process continue into the fourth year. PMID- 7865042 TI - The relationship of indebtedness, race, and gender to the choice of general or subspecialty pediatrics. AB - BACKGROUND: Little research has examined indebtedness and the choice of continued subspecialty training. Concerns about a decline in the proportion of primary care physicians obliges medical educators to understand factors that influence the choice of subspecialty training. METHOD: Survey data on 437 pediatricians who graduated between the years 1981 and 1987 were collected in 1991. Logistic regression was used to examine the influences of sex, race, graduation year, type of medical school, and educational debt (adjusted for inflation) on whether a pediatrician had trained in a subspecialty. RESULTS: Three variables were associated with subspecialty training. Men and whites were significantly more likely to have trained in subspecialties, as were earlier graduates. Type of medical school and debt did not enter the equation. CONCLUSION: Other variables were found to be more influential than indebtedness in the career decisions of primary care and subspecialty pediatricians. Distinguishing between subspecialties that have noticeably higher incomes and those that serve to enhance primary care pediatrics may be illuminating. That men and whites were more likely to train in subspecialty pediatrics suggests that financial considerations, if present, may be masked under other cultural and societal factors. PMID- 7865043 TI - Evaluating medical residents' literature-appraisal skills. AB - BACKGROUND: Measuring critical-appraisal skills is a key step in assessing physicians' abilities to engage in self-directed learning. The authors developed an instrument to evaluate the abilities of residents to critically appraise a journal article. METHOD: In 1991, 62 residents in the categorical internal medicine program at the New England Medical Center were asked to respond to a questionnaire, evaluate a sample article, and complete a self-assessment of competence in evaluation of research. Critical-appraisal skill was determined by calculating the resident's deviations from a "gold standard" critique developed through a modified Delphi technique, using a panel of five physicians. Spearman correlation coefficients were used to compare the residents' actual and self perceived abilities. RESULTS: Twenty-eight residents returned the questionnaire, for a response rate of 45%. The composite score for the residents' objective assessments was 63% of the gold standard, and was not significantly correlated with post-graduate year, prior journal club experience, or self-assessed critical appraisal skill. CONCLUSION: After further validation in other settings, the assessment instrument in this study may be used to objectively assess critical reading skills. It may also provide feedback and measure outcomes for interventions designed to improve critical reading. PMID- 7865044 TI - A strategy for improving the supervision and performance of moonlighting residents. AB - BACKGROUND: In 1990 the Ambulatory Care Service of the Ralph H. Johnson Department of Veterans Affairs Medical Center, affiliated with the Medical University of South Carolina College of Medicine, developed written clinical protocols for the management of patients with certain high-risk medical conditions. METHOD: Appropriateness of care was assessed by determining physician compliance to the protocols over a 24-month period (October 1990-September 1992). All physicians who did not comply received individualized feedback from the service chief. For the first 12 months, both staff physicians and moonlighting second- and third-year medical residents were assessed (a total of seven staff physicians and 20 residents participated in the study). For the second 12 months, only the residents were assessed. RESULTS: The moonlighting residents were notably less consistent than the staff physicians in protocol compliance (95-100% for the staff physicians; 78-100% for the moonlighters). Additional interventions were then implemented to improve the moonlighters' utilization of the protocols. Moonlighters' compliance over the subsequent 12 months was less variable (mean compliance of 92%, SD, 3%, the first year versus 95%, SD, 8%, the second year). CONCLUSION: The strategy seemed to improve the supervision and performance of the moonlighting residents and promoted consistent delivery of high-quality outpatient care. PMID- 7865045 TI - Using electronic mail for a small-group curriculum in ethical and social issues. AB - PURPOSE: To initiate an electronic mail (e-mail) program as a supplement to a medical humanities curriculum focusing on ethical and social issues. METHOD: In 1991-92 an e-mail track (called NET) was established for second-year students participating in Medicine in Contemporary Society, a four-year curriculum in medical humanities at the State University of New York at Stony Brook School of Medicine. In 1991-92 ten students volunteered to form a NET group; in 1992-93 22 students, forming two groups, were randomly selected from a volunteer pool of 76 students (from a class of 100). In both study years, the NET students analyzed and discussed electronically a series of cases posted sequentially through the academic year. Faculty tutors reviewed the students' responses, interacting with the groups and with individual students by e-mail. NET was evaluated in two ways: at the end of the course, the students completed e-mail questionnaires that included quantitative and qualitative assessments; and throughout the course, the tutors assessed the students' participation, quality of case analysis and discussion, and quality of writing. RESULTS: The students' assessments indicated that they considered NET to be more educational than the lectures, "live" group discussions, problem-based learning exercises, and formal papers in the medical humanities curriculum; that they made gains in computer literacy; and that NET enhanced their abilities to think about ethical and social issues. The tutors judged that the students had improved their written self-expression as the course progressed. CONCLUSION: NET adequately accomplished the goals set for it as an adjunct to the small-group sessions and other components of the medical humanities curriculum. PMID- 7865046 TI - Self-directed learning in problem-based health sciences education. AB - PURPOSE: To determine the amounts of time that physiotherapy (PT) and occupational therapy (OT) students in problem-based curricula spent in non scheduled and scheduled educational activities, and to determine whether the students increased or decreased the time spent in educational activities as they progressed through the curricula. METHOD: The participants were the 29 PT and 29 OT students in the classes of 1992 in the two-year problem-based educational programs at McMaster University. Each student was randomly assigned to different days of the week to record his or her time utilization for a 24-hour period in each of weeks three, seven, and 11 of the second, fourth, and sixth units of the seven-unit curricula. Weeks 11 of the second and fourth units emphasized clinical education; the other weeks involved academic study only. RESULTS: During the academic weeks, the grand ratios of non-scheduled to scheduled time were 2.8:1 for the PT students and 2.9:1 for the OT students. During the two weeks focusing on clinical education, the ratios were lower: 0.4:1 and 0.2:1 for the PT students, and 1:1 and 0.8:1 for the OT students (the discrepancy between the groups may be due to the fact that the OT students had academic assignments during their clinical placements, while the PT students did not). As the students proceeded through the programs, a general decrease in time spent in educational activities was noted. CONCLUSION: The general decrease in time spent in educational activities as the students progressed through the programs was probably due to their becoming familiar with expectations and their gaining efficiency in using learning resources. PMID- 7865047 TI - Perceptions of the educational contract among Saudi residents and western staff physicians in Saudi Arabia. AB - BACKGROUND: Approved residency programs are increasingly being set up in Saudi Arabia and require that many Western staff physicians be rapidly deployed. METHOD: A non-university hospital in Saudi Arabia that employs several expatriate staff physicians undertook focused program evaluations of residencies in four disciplines in 1991 and again in 1992. Interviews, written comments, and questionnaires were used to collect residents' ratings of their training and clinical instructors and the residents' and staff physicians' perceptions regarding their educational contract, i.e., the personal agreement between teachers and learners. According to educational contract theory, clinical teachers adopt three basic roles (expert, model, or facilitator), as do residents (dependent, competitive, or participant). Chi-square with Yates' correction was used for statistical analysis. RESULTS: All 137 possible responses were returned (72 in 1991 and 65 in 1992). In 1991 the residents and staff physicians perceived the Saudi residents as mostly dependent, and 71% of the residents thought that the staff physicians were experts or models. This percentage conflicted with the staff physicians' own perceptions of their role as facilitators (46%). In 1992 the staff physicians increasingly perceived the residents as competitive (from 5% in 1991 to 10% in 1992), and the residents increasingly perceived the staff physicians to be facilitators (from 28% to 50%). CONCLUSION: The study compelled the staff physicians and residents to reexamine their perceptions of the educational contract between them. The resultant tendency toward convergence of perception was instructive and mutually beneficial. PMID- 7865048 TI - Evaluation of medical knowledge in an undergraduate ambulatory care experience. PMID- 7865049 TI - An instrument to assess the outcomes of a teacher education program for residents. PMID- 7865050 TI - A single-session exercise to address medical residents' attitudes toward work disability evaluations. PMID- 7865051 TI - Factors that predict medical students' interest in rural practice. PMID- 7865052 TI - Another look at declining recertification scores. PMID- 7865053 TI - A useful way to orient students to medical careers. PMID- 7865054 TI - Undergraduate course in ambulatory care. PMID- 7865055 TI - Psychological testing for family practice residents. PMID- 7865056 TI - Not enough light for medical students? PMID- 7865057 TI - A view from the future: the challenge for academic medicine in northern California. PMID- 7865058 TI - A worthy search: the development of the key-features concept. PMID- 7865059 TI - Breach of contract. PMID- 7865060 TI - Health care reform continues: themes for academic medicine. AB - The challenge for U.S. academic medicine in this decade is to redesign itself to serve its classic functions--teaching, research, and special service to patients- while filling the needs of what is evolving into a comprehensive integrated system of health care. First, in the absence of federally legislated comprehensive health care reform, the health care community must develop a consensus on the purposes, scope, and content of health care to bring some reason and order to the short-term, market-driven incrementalism that governs today's health care. Specifically, the author proposes that the issues of health care be defined in a broad social context, that the gap between public health and medicine be lessened, and that perspectives of public health and health promotion and disease prevention be more effectively incorporated into medical education. Second, there is an urgent need for new approaches to funding and financial management of teaching, research, and patient care in academic health centers to counter the erosion of traditional sources of support. Third, to sustain generalist physician practices of high quality, a conceptual basis for generalism must be defined in affirmative functional terms, and the generalist's frame of reference and intellectual tools and processes must be formulated. Last, many forces are now acting to reduce the intellectual content of medical practice and teaching. Academic medicine--in teaching and in research--must nurture and promote the intellectual content and standards of all aspects of medicine to sustain the quality of clinical practice over time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865061 TI - Finding the silver lining without the golden eggs. AB - Despite the failure of Congress to enact comprehensive health care reform legislation, including the hard-won proposals on behalf of academic medicine, there is much reason for hope for the future. Academic medicine won major victories in having its proposals for a broad-based all-payer system of explicit supports for its various missions included in major reform bills. If the members of the academic medicine community can strengthen further the unity they achieved during the long debate, they will be well positioned to succeed if another opportunity arises in time to rescue academic medicine from a buyer's market that is indifferent to their needs. But prudence dictates that they not depend on being rescued and instead consider the faltering of legislative reform as a wake up call, summoning them to focus on difficult issues within their own control as they engage the rapidly changing health-care marketplace. Academic medicine has grown phenomenally over the past few decades because its missions have been strongly supported by the public. Continued growth is unlikely, given society's numerous unmet needs and limited resources. Therefore, academic medicine not only must face squarely the challenge of restructuring its work to be more efficient and more productive, but must use the many opportunities that lie ahead to sustain and strengthen its public support by embracing public accountability and rededicating its efforts to meet public expectations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865062 TI - [Mechanomyographic and electromyographic studies of endotracheal intubation with 2 different rocuronium dosages]. AB - Rocuronium is a new, intermediate-acting, nondepolarizing relaxant with rapid onset of action leading to both good and very good intubation conditions. It was the aim of our study to investigate the onset of action, the intubation conditions and the course of relaxation using two different dosage regimes. Thirty consenting ASA 1 and 2 patients received either 0.6 mg/kg (2 x ED 95; group 1) or 0.06 mg/kg as priming dose followed by an intubating dose of 0.24 mg/kg rocuronium (group 2) four min later. Anaesthesia was induced with propofol (2 mg/kg) and alfentanil (0.02 mg/kg) and maintained with nitrous oxide/oxygen and propofol (6 to 8 mg/kg/h). Neuromuscular function was monitored mechanomyographically and electromyographically with TOF stimulation at the wrist every 10 seconds. Intubation conditions were determined using a semiquantitative score system, and times to 90% block (intubation time), maximum block (onset time) and recovery from neuromuscular blockade to 25%, 50%, 75% and 90% were calculated and comparisons were made between the corresponding results of the two groups. The intubation dose of 2 x ED 95 (group 1) was followed by a significantly shorter intubation time (39.1 +/- 9.6 sec.) than in group 2 with priming and an intubation dose of 0.24 mg/kg (50.7 +/- 11.0 sec). The intubation conditions showed no differences. In both groups they were good or very good. The clinical duration of action was significantly longer in group 1 (28.4 +/- 8.0 min) than in group 2 (14.8 +/- 2.5 min). It can be concluded that rocuronium which has shorter intubation times than atracurium and vecuronium is very useful for endotracheal intubation in both dosage regimes in long and very long lasting operations. Using the "priming principle" the patient has to be carefully controlled during priming time. PMID- 7865063 TI - [Anesthesia with the closed PhysioFlex system in comparison with conventional anesthesia procedures]. AB - So far the anaesthetic technique of the closed circuit system in clinical routine could not be used adequately, because suitable mixtures of respiration gas components were not available and the maintenance of a sufficient gas volume in the anaesthetic circle system was not possible with the standard anaesthesia machines. The anaesthesia machine PhysioFlex was especially constructed to deliver anaesthetics in a closed circuit system. In this anaesthesia machine the concentrations of the respiratory gases and the gas volume in the circle system are automatically controlled by a feedback mechanism. We compared the closed circuit system (CC group), with a high-flow system (HF group) and a low-flow system (LF group)--each system on 10 patients. It was noted that the respiratory gas concentrations were adjustable and held constant to a greater degree precise in the circuit system. After the induction the desired inspiratory oxygen concentration was reached within 5 minutes, the expiratory isoflurane concentration within 10 minutes in the CC group and was maintained reliable. The consumption of liquid isoflurane was 12.9 ml/h in the HF group, 7.5 ml/h in the LF group and 5.3 ml/h in the CC group. The anaesthetic management was possible without any problems in all three groups. PMID- 7865064 TI - [Left heart failure in anesthesia in a child pretreated with propranolol--case report]. AB - A 13-year-old girl suffering from nephrogenic hypertension, treated with high dose propranolol and other antihypertensive medication, developed acute hypoxaemia (oxygen saturation at 60% at 100% oxygen ventilation) shortly after induction of anaesthesia. The auscultatory findings first suggested bronchospasm; however, specific measures failed to improve pulmonary function. The planned procedure was delayed and further investigations showed acute left heart failure due to beta-blockade combining with general anaesthesia. PMID- 7865065 TI - [Toxic shock syndrome caused by Streptococcus pyogenes]. AB - Necrotizing fasciitis and myositis due to Lancefield group A beta-haemolytic streptococcal infection is a medical emergency. Survival depends on aggressive early wound management as well as high-dose intravenous antibiotics. We report about a 28-year-old man with fulminant necrotizing fasciitis and myositis of his right arm, in whom many features of the toxic shock syndrome were present, including profound hypotension and renal failure. After extensive surgical debridement with amputation of his arm in combination with high-dose intravenous penicillin G the patient recovered from this serious infection. PMID- 7865066 TI - Symposium on Mechanisms and Agents in Preventive Dentistry. Proceedings. Chester, England, October 28-November 1, 1992. PMID- 7865067 TI - In situ models, physico-chemical aspects. AB - In situ (intra-oral) caries models are used for two purposes. First, they provide information about oral physiological processes. Such information helps to detail our knowledge of the oral ecosystem and to verify conclusions from in vitro experiments. Second, in situ models are utilized to test preventive agents in the phase between laboratory testing and clinical trials. Most investigations involving enamel inserts have been aimed at testing new dentifrices. The experimental designs of such studies usually do not allow one to draw conclusions on physico-chemical processes, e.g., because of single point measurements. Studies of model parameters (lesion type, lesion severity, and de/remineralization in time) constitute only a minority of the research reports. The most striking observation obtained with in situ models has been the significant differences in de/remineralization observed among individuals and, more importantly, within one individual during different time periods and between different sites in the same mouth (for review, see ten Cate et al., 1992). Regardless of this, some general findings can be inferred: During in situ demineralization, up to 62 vol% microns/day may be removed from enamel. For dentin specimens, this value may be as high as 89 vol% microns/day. For remineralization, during fluoride dentifrice treatment, a median deposition rate of 0.7%/day (for lesions with integrated mineral loss values between 2000 and 4000 vol% microns) is found. The rate of deposition seems to be correlated with the extent of the pre-formed lesion. This suggests that the number of sites (crystallite surface) available for calcium phosphate precipitation is an important parameter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865068 TI - Human experimental caries models: intra-oral environmental variability. AB - In situ caries models serve purposes other than just being a simpler way to obtain data than running a clinical trial. However, variation in information obtained not only among individuals but also, in particular, depending on different locations of the models within the oral cavity have so far been given little attention. In the present review, the aim has been to characterize the different designs of in situ caries models and to describe some important factors which may vary within the oral cavity and thus influence the outcome of the way the different in situ models are used. Advantages and disadvantages of in vivo models vs. in situ models are discussed. In the latter case, the distinction is made between dental appliance models and so-called "single tooth" models. The review concludes that in situ models differ distinctly with regard to their "biological potential". Because of regional differences in salivary film velocity, pH, and composition of the microflora, results obtained by the various models are not likely to be immediately comparable. Moreover, local factors in relation to specimen environment, such as degree of "protection" and plaque thickness, may further add to the differences. It is suggested that these observations are important in considerations of the relevance of substituting clinical trials with in situ studies. Because of the pronounced intra-oral variation in certain parameters thought to be important for caries lesion development, we conclude that no in situ model can, by itself, fulfill the role as the "model of choice". Finally, although in situ models are useful adjuncts in attempts to estimate the relative effects of new anticaries methods or compounds on caries initiation, the selection of in situ study model design will strongly depend on the aim and purpose of the study. PMID- 7865069 TI - In vivo caries models--mechanisms for caries initiation and arrestment. AB - The effects of intra-oral mechanical forces on caries initiation, progression, and arrestment are evaluated by examination of different in vivo caries models. The models are grouped in four categories: (1) a population study, (2) short-term clinical trials, (3) clinical experiments, and (4) controlled clinical observations. Taken together, these in vivo studies convincingly demonstrate that partial or total elimination of the intra-oral mechanical forces operating during mastication or toothbrushing leads to evolution of cariogenic plaque, resulting in localized carious enamel dissolution. In addition, they show that re-exposure to the partly or totally eliminated mechanical forces not only arrests further lesion progression, but also results in partial lesion regression. The data from in vivo caries studies also show that the clinical and structural changes associated with lesion arrestment or partial regression are not related to any salivary repair mechanism, but are solely the result of mechanical removal of the cariogenic biomass which is physically interrelated with the eroded surface of the active, dull-whitish enamel lesion. No indications of superficial mineral deposition or "blocking" of the external intercrystalline spaces are seen in the surface layer of lesions arrested in vivo. For this reason, the conventional usage of the terminology 'remineralization' is considered absolutely misleading when used to describe the mechanisms responsible for the arrest of lesion progression in vivo. PMID- 7865070 TI - Interactions of fluoride and non-fluoride agents with the caries process. AB - Fundamental to the caries process and its inhibition is an understanding of the composition and structural relationships of dental mineral. These have received greater study in recent years, leading to a better understanding of the processes involved. Fluoride has been the most successful of the anti-caries agents to date, and many studies have concentrated on this ion. The anti-caries action of fluoride has been only partially explained by the early finding that fluoride treated mineral was less soluble, and this criterion is now less widely accepted. The dissolutive process of caries is inhibited by fluoride, monofluorophosphate, trimetaphosphate, and zinc. However, only the first three of these show anti caries activity. The presence of fluoride during in vivo and in vitro caries is conducive to the formation of an apparently intact surface zone. Current evidence is that this zone reforms during the caries process, thus acquiring fluoride and having larger crystallites compared with sound enamel. Trimetaphosphate also favors the formation of a surface zone. There is a clear beneficial involvement of fluoride, even at low levels, in the process of lesion remineralization. It is highly probable that this process results from re-growth of residual enamel crystallites rather than de novo precipitation of calcium phosphates. Levels of fluoride found in saliva can interact with dental mineral. Although zinc has been shown to adsorb upon apatite mineral and to restrict subsequent crystal growth, it does not appear to affect the action of fluoride, including remineralization, adversely. This may be due to the fact that the uptake of zinc is reversible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865071 TI - Mode of action of fluoride: application of new techniques and test methods to the examination of the mechanism of action of topical fluoride. AB - Modern techniques in dental research continue to assist in the study of the mode of (anticaries) action of topical fluorides. The Plaque Glycolysis and Regrowth Model (PGRM) facilitates the standardized assessments of antimicrobial effects on plaque following use of test formulations in vivo without complications arising from coincident mineral reactivity. In vivo plaque glycolysis testing demonstrates that topically applied fluoride, at conventional levels found in dentifrices, has only modest effects on the metabolic (acid-producing) activity of dental plaque. Any 'plaque' contribution to fluoride efficacy must come from more subtle effects on plaque acidogenicity than those measured in PGRM. The 19 FMAS NMR (Magic Angle Spinning Nuclear Magnetic Resonance) technique provides unambiguous measures of the reaction products of F-enamel interactions. Studies have revealed a new 'reaction product' of fluoride-enamel interactions- designated as Non-Specifically-Adsorbed Fluoride, NSAF. This species, along with FAP (fluoroapatite), FHAP (fluorohydroxyapatite), and CaF2 (calcium fluoride), contributes to the remineralization/demineralization benefits of fluoride. pH cycling and in situ denture chip studies permit quantitative assessments to be made of the relative benefits of fluoride in promoting remineralization and in inhibiting demineralization. Results from pH cycling/in situ experiments are strongly supportive of Koulourides' 'Acquired Acid Resistance' concept, describing fluoride's decay-preventive effects. The continued application of new analytical/physical techniques and testing regimens to the study of fluoride anticaries mechanisms may lead to the development of improved fluoride agents/treatment modalities for the prevention of dental caries. PMID- 7865073 TI - Systemic fluorides. AB - Fluoridation of domestic water supplies has been shown to be effective in reducing the prevalence of dental caries in numerous studies conducted world-wide over the last 50 years. The most widely used systemic alternative to water fluoridation is salt fluoridation, which has been found to be effective against dental caries in programs conducted in Switzerland and Hungary. Currently, fluoridated salt is sold in eight countries. Studies conducted on fluoridated milk in Scotland, Hungary, and Bulgaria have shown it to be effective against dental caries, and a number of fluoridated milk programs are currently at the planning stage. The feasibility of using fluoridated sugar in communities where alternative preventive strategies are not feasible is currently being investigated. PMID- 7865072 TI - Absorption and retention of dietary and supplemental fluoride by infants. AB - There is a widespread belief that an adequate intake of fluoride during the pre eruptive stage of enamel formation (i.e., from the diet in frequent small doses throughout the day) will be protective against caries in later life. To obtain data on bio-availability and retention of fluoride in one age group (infants), we studied 3 treatment regimens: In Regimen A, small amounts of fluoride were obtained from the diet in frequent doses throughout the day; in Regimen B, a fluoride supplement (0.25 mg) was given once each day with a feeding; Regimen C was similar to regimen B except that the fluoride supplement was given 1 h before a feeding. For the 3 regimens, the respective mean absorptions of fluoride were 90.1, 88.9, and 96.0% of intake, and the respective retentions were 12.5, 47.1, and 52.3% of intake. Neither the difference in absorption nor the difference in retention between regimens B and C was statistically significant. By subtracting the background urinary excretion of fluoride (i.e., excretion of fluoride while diet was the sole source of fluoride) from the excretion after administration of the fluoride supplement, we calculated that 68.1% of the supplement was retained in Regimen B and 73.0% of the supplement in Regimen C. The difference was not significant. PMID- 7865074 TI - Fluoride toothpastes, rinses, and tablets. AB - Only from the mid-1950's has therapeutic benefit been obtained via dentifrices, initially with stannous fluoride-then monofluorophosphate-containing products which remained stable and efficacious. Altered abrasive systems followed, and both sodium fluoride and monofluorophosphate/sodium fluoride mixtures were introduced as active anti-caries agents, with recent meta-analysis indicating that sodium fluoride > monofluorophosphate/sodium fluoride > monofluorophosphate. With respect to fluoride levels, clear dose-response relationships have been demonstrated. However, at < 1000 ppm F, the situation is less certain. Since the mid-1980's, anticalculus fluoride dentifrices have been marketed, and have been shown to have similar caries-reducing potential as their non-calculus-inhibiting control formulae. Finally, one study has been described where a sodium fluoride dentifrice successfully reduced root caries. Of the many fluoride formulations used for caries-inhibiting mouthrinsing [e.g., acid phosphate fluoride (100-3000 ppm F), sodium fluoride (45-3000 ppm F), stannous fluoride (100-250 ppm F), ammonium fluoride (1000 ppm F), and amine fluoride (250 ppm F)], sodium fluoride would seem to be the preferred agent. Furthermore, rinse frequency is deemed more important than fluoride ion concentration, but caution is urged re the volumes and concentrations to be used by children, no rinsing being recommended below 4 years. Combination of a 440-pp-F sodium fluoride and 0.05% chlorhexidine school administered rinse appears to have increased the caries-inhibiting benefit as compared with sodium fluoride alone. Fluoride supplements have reduced deciduous caries from 14 to 93%, and in the permanent dentition, from 20 to 81%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865075 TI - Professional topical fluoride applications--clinical efficacy and mechanism of action. AB - All currently used topical fluoride agents deposit soluble fluoride as calcium fluoride on enamel or in lesions. Calcium fluoride serves as a source of fluoride for the formation of fluorapatite. The latter phase is formed when pH drops in plaque, not during topical application. The potential for calcium fluoride formation should probably be increased in topical fluoride agents. In countries with low caries prevalence, the clinical recommendations for topical fluoride need to be reconsidered. Toothpaste is the basic fluoride regimen recommended for everybody. The need for additional fluoride supplementation depends on caries activity. There is no distinct difference in the caries-preventive effects of concentrated fluoride solutions, gels, or varnishes. Thus, the choice of method depends on costs, convenience, patient acceptance, and safety. The use of fluoride varnishes has proven to be a feasible and safe method of fluoride application. With fluoride varnishes, the amounts of fluoride exposure can be better controlled, and less chair-time is required compared with conventional solutions and gels. No dose-response effect to concentrated fluoride agents is apparent, and the benefit of frequent application is not clearly established. In individuals with the most severe cariogenic challenge, combinations of fluoride and antimicrobials may give better clinical effects than fluoride alone. PMID- 7865076 TI - Studies on plaque fluoride after use of F-containing dentifrices. AB - Increased fluoride levels in plaque and saliva have been associated with improved protection against dental caries for dentifrices which contained sodium monofluorophosphate (Duckworth et al., 1992). The main aim of the present work was to test whether oral fluoride retention depended on F source after use of dentifrices containing either NaF or Na2FPO3. In study 1, plaque samples were collected from 474 subjects who had been using one of six test dentifrices for two years, and analyzed by F extraction with water. The dentifrices contained 1000 or 1500 micrograms F/g as either NaF or Na2FPO3. Significantly more fluoride was found in plaque from subjects who were using the NaF dentifrices than in plaque from subjects who were using Na2FPO3 dentifrices of the same F content. Subsets of plaque samples were large enough to divide into two parts for extraction by both acid and water. No significant difference was found between mean fluoride contents, indicating that the majority of fluoride retained in plaque from these conventional dentifrices appears to be relatively labile. The results of two small-scale human enamel studies showed that NaF dentifrices gave elevated F concentrations in plaque and saliva, respectively, compared with Na2FPO3 dentifrices of equivalent F content, consistent with the main plaque study 1. These findings demonstrate that oral F retention from dentifrices is dependent on the source of ionic fluoride and support the view that NaF dentifrices may be more clinically effective than dentifrices which contain the same amount of F as Na2FPO3. PMID- 7865077 TI - Non-fluoride anticaries agents. AB - Many potential anticaries agents other than fluoride have been identified in a range of laboratory models. This review covers only those agents which have demonstrated significant activity in either animal caries models, in situ models, or human clinical trials, including those measuring plaque acid formation. The agents which so far have been identified can be divided into 5 categories: (1) phosphorus-containing agents, (2) calcium-containing agents, (3) antimicrobials and antibiotics, (4) metals, and (5) miscellaneous agents. Although many potential agents have been identified in various models, very few have been taken forward to full anticaries testing in humans. Chlorhexidine is an exception, and certain agents such as calcium glycerophosphate have been shown to result in greater anticaries activity when added to fluoride. In the future, non-fluoride agents which modify the production of acid in plaque--either antimicrobially, biochemically, or directly--appear to have the most promise for use in topical products and may prove to be effective anticaries systems. Phosphates have shown encouraging activity as diet additives. PMID- 7865078 TI - Food components and caries. AB - For many decades, sugars have been the dietary constituents receiving the most attention in relation to their effects on dental caries. Frequently, however, there is little relationship between the amount of sugar in a food and its ability to induce caries. Therefore, it is clear that constituents in the diet can influence the ability of plaque to lower the pH of sugar solutions. For instance, replacing sugar in foods with xylitol, sorbitol, saccharin, or aspartame may lead to a reduction in the incidence of dental caries. All these sugar substitutes are non-cariogenic, and some may possess cariostatic properties. The presence of arginine-rich proteins in the diet may provide a ready source of this amino acid, which is the substrate for the arginine deiminase pathway which can result in a rapid elevation of plaque pH values. Proline can act as an acceptor for protons from lactate in the Stickland reaction. This is a major but much-neglected metabolic pathway in dental plaque. The presence of fat in experimental diets has been shown to affect their cariogenicity. The effects have been ascribed to enhanced clearance of sugars from the mouth. It is also conceivable that several fatty acids express a potent antibacterial effect. The presence of calcium and phosphorus has been shown to influence the cariogenicity of foods; the effect, however, is restricted to the food containing the minerals. Evidence suggests that pyridoxine (vitamin B6) may exert a cariostatic effect by enhancing decarboxylation activity in dental plaque. It is clear that sugar alone is not the sole determinant of whether food is cariogenic. Furthermore, myriad substances may hinder or enhance the caries promoting properties of sugars in the diet. PMID- 7865079 TI - Diet patterns and caries. AB - Few dietary studies have been designed to investigate the effects of intake patterns of food items upon the environment of the teeth. This brief review considers evidence about the effects of choice, combination, and sequence of ingested food and drink upon the pH of human dental plaque in vivo. A series of three studies, which were designed to investigate some of the intra-oral biological events associated with cariogenicity during various eating patterns, are discussed. The principal findings show that if a "meal" includes an item which contains carbohydrate such as sucrose, glucose, or fructose which is rapidly fermented by the acidogenic microorganisms in dental plaque, there will be rapid acid production and the plaque pH will fall. However, other items eaten immediately before, during, or after the consumption of the sugary item can influence the plaque pH. If the non-sugary item stimulates saliva, it will have a pH-raising effect. The remineralizing potential may be enhanced if, for instance, calcium or fluoride is released from the food. However, if one sugary item is followed by another, the demineralizing potential may be enhanced. The results of these experiments are discussed in the context of our current understanding of the dynamics of the carious process. Recent preliminary experiments suggest that other factors, such as the individual subject's speed of consumption, may also affect the cariogenic potential of the oral environment. PMID- 7865080 TI - Cariogenicity tests. AB - An American Dental Association Scientific Consensus Conference on Methods for the Assessment of the Cariogenic Potential (CP) of Foods was held in San Antonio, Texas, in 1985. The aim was to establish a scientific consensus regarding methods to assess the CP of foods. As a result, a sequential food-testing program was proposed involving Animal Caries, Human Plaque Acidity, and Demineralization/Remineralization Models. Two categories of CP--namely, no CP and low CP--were included. The test protocol has hardly been followed since, primarily because the category of low CP was not considered useful in dietary counseling. It is advocated that research into possible caries-preventive factors of food will be more beneficial for improvements of the oral health of the general population than assessments of low CP. PMID- 7865081 TI - Caries-protective factors in saliva. AB - Saliva influences caries attack mainly by its rate of flow and by its content of fluoride. The salivary flow rate influences to a high degree the rate of oral and salivary clearance of bacterial substrates included in foods and snacks. This influence is site-dependent. The basal salivary fluoride concentration is low, about 1 mumol/L, independent of salivary flow rate, and not influenced by diurnal variation. After an exposure of the oral cavity to fluoride, the increased fluoride level is decreased by a process influenced mainly by the salivary flow rate and the volumes of saliva in the mouth before and after swallowing. Other less important caries-protective factors in saliva include its buffer ability, its content of calcium, inorganic phosphate, pH-increasing substances, and anti microbial agents. PMID- 7865082 TI - Saliva stimulation and caries prevention. AB - The protective role of saliva is demonstrated by the rampant caries seen in human subjects with marked salivary hypofunction, and in desalivated animals. In normal cases, however, the relationship between saliva flow and coronal or root caries experience is doubtful, and to examine the concept that stimulation of saliva might have protective effects against caries, one must look beyond a simple correlation between caries and flow rate. Protective properties of saliva which increase on stimulation include salivary clearance, buffering power, and degree of saturation with respect to tooth mineral. These benefits are maximized when saliva is stimulated after the consumption of fermentable carbohydrates, by reducing the fall in plaque pH leading to demineralization and by increasing the potential for remineralization. Plaque acid production is neutralized, and experimental lesions in enamel are remineralized, when gum is chewed to stimulate saliva after a carbohydrate intake. The pH-raising effects are more easily explained by the buffering action of the stimulated saliva than by clearance of carbohydrates. The remineralization action depends upon the presence of fluoride. These findings suggest that the protective actions of saliva can be mobilized by appropriate salivary stimulation, and that in addition to established procedures such as tooth cleaning and fluoride regimens, eating patterns which lead to saliva stimulation to increase the potential for saliva protection might be included in recommendations for caries prevention. Confirmation of this concept in clinical tests is required. PMID- 7865083 TI - Mechanisms of dental plaque formation. AB - Much effort has been placed on elucidating the diverse mechanisms of microbial adhesion to tooth surfaces. Both specific and non-specific types of adhesion have been envisaged. Pioneer colonizers represent a selected part of the oral microflora, and it has been assumed that specific adhesin-receptor interactions between the microbial surface and the pellicle account for this specificity. Whereas microbial adhesion to tooth surfaces is a general prerequisite for initiation of plaque formation, microbial multiplication is probably the dominant feature in the build-up of dental plaque. Local environmental factors which influence the establishment and composition of the ultimate plaque community are therefore of greater importance than initial adhesion per se. The highly individual and site-related characteristics of the plaque flora illustrate the selective power of the environment. Environmental conditions are not uniform. Thus, each site represents its own conditions are not uniform. Thus, each site represents its own distinct ecosystem, and the microbial composition at the site depends on the outcome of a variety of host-microbial and microbial-microbial interactions. The relative in vivo significance of these interactions is difficult to assess. PMID- 7865084 TI - Bacterial-protein interactions in the oral cavity. AB - Bacteria in the oral cavity must interact with salivary proteins if they are to survive. Such interactions can take several forms, either providing nutrients, a means of adhesion to surfaces, or resulting in aggregation or killing and, therefore, clearance of organisms. Recent work has provided an insight into the mechanisms of some of these bacterial-protein interactions, revealing complexity and diversity. For example, the interaction between a putative Streptococcus mutans adhesin, P1 (B, I/II, etc.), and a parotid glycoprotein results in adhesion when it occurs at a surface or aggregation when in solution, and different domains of P1 appear to be involved in the two processes. An alternative strategy is employed by Actinomyces viscosus, which interacts, via its type-1 fimbriae, with a proline-rich salivary protein; however, this interaction occurs only when the PRP is adsorbed to a surface. A. viscosus takes advantage of a conformational change in the PRP when it becomes surface-bound, which exposes a cryptic part of the molecule. A third, and intriguing, type of interaction is seen between various streptococci and salivary amylase. This does not result in either adherence or aggregation but provides organisms with the ability to utilize starch breakdown products for metabolism. An understanding of the mechanisms involved in bacterial-protein interactions could conceivably lead to novel methods for controlling specific pathogens, but the systems operating in the mouth are numerous, complex, and diverse. PMID- 7865085 TI - Microbial ecology of dental plaque and its significance in health and disease. AB - Dental plaque forms naturally on teeth and is of benefit to the host by helping to prevent colonization by exogenous species. The bacterial composition of plaque remains relatively stable despite regular exposure to minor environmental perturbations. This stability (microbial homeostasis) is due in part to a dynamic balance of both synergistic and antagonistic microbial interactions. However, homeostasis can break down, leading to shifts in the balance of the microflora, thereby predisposing sites to disease. For example, the frequent exposure of plaque to low pH leads to inhibition of acid-sensitive species and the selection of organisms with an aciduric physiology, such as mutans streptococci and lactobacilli. Similarly, plaque accumulation around the gingival margin leads to an inflammatory host response and an increased flow of gingival crevicular fluid. The subgingival microflora shifts from being mainly Gram-positive to being comprised of increased levels of obligately anaerobic, asaccharolytic Gram negative organisms. It is proposed that disease can be prevented or treated not only by targeting the putative pathogens but also by interfering with the processes that drive the breakdown in homeostasis. Thus, the rate of acid production following sugar intake could be reduced by fluoride, alternative sweeteners, and low concentrations of antimicrobial agents, while oxygenating or redox agents could raise the Eh of periodontal pockets and prevent the growth and metabolism of obligately anaerobic species. These views have been incorporated into a modified hypothesis (the "ecological plaque hypothesis") to explain the relationship between the plaque microflora and the host in health and disease, and to identify new strategies for disease prevention. PMID- 7865086 TI - Polydimethylsiloxane as a tooth surface-bound carrier of triclosan: a new concept in chemical plaque inhibition. AB - Polydimethylsiloxane (silicone oil) has an extremely low surface tension: It spreads over solid surfaces and forms a tenacious film which is hydrophobic and water-repellent. It is known that this liquid binds to hydroxyapatite and to dental enamel and changes the properties of these solids. It has been suggested that silicone oil may be applied to teeth and serve as a reservoir of lipid soluble antibacterial substances which presumably will be slowly released into saliva due to their low solubility in water. The present paper reviews recent papers where this hypothesis is tested in vitro and in vivo. It was first shown that test tubes treated with the combination silicone oil and the lipid-soluble agent triclosan acquired a layer which inhibited bacterial growth in a culture of Streptococcus sobrinus (OMZ 176) which was grown in sucrose. Both growth in the medium and polysaccharide adsorption to the glass wall were inhibited. Silicone oil alone inhibited polysaccharide adsorption to some degree, whereas the growth in the medium was not affected. In a similar clinical plaque-inhibition study, topical application of silicone oil/triclosan to the teeth of a test panel showed marked plaque inhibition, particularly giving an increased number of teeth with scores of 0 (no plaque). In a study where silicone oil and triclosan were incorporated into a toothpaste, improved gingival health was observed after a period of one month. It is concluded that the use of silicone oil/triclosan in the manner described above represents a new principle in preventive dentistry. The results obtained seem to warrant further experiments with this combination. PMID- 7865087 TI - The effect of a new oral hygiene training program on approximal caries in 12-15 year-old Brazilian children: results after three years. AB - This study evaluated the effects of a new oral hygiene training program on approximal caries in a population of 12-13-year-old Brazilian schoolchildren with a well-established habit of daily toothbrushing with a F dentifrice. Two hundred twenty-two children were randomly allocated into two test groups (I and II) and one control group (III). Group I subjects were trained to establish needs-related oral hygiene habits based on self-diagnosis and a new behavioral principle, the 'linking method', for establishment of habits. The first three visits (20 minutes each) were scheduled at two-day intervals. They were recalled for a monthly check up during the first 4 months, and then every 3 months for reevaluation of the results based on self-diagnosis. Group II subjects were recalled at the same intervals for detailed oral hygiene instruction on how to clean every tooth surface using dental tape, toothbrush, and fluoride dentifrice. Group I developed significantly fewer (p < 0.001) new approximal manifest (dentin) caries lesions than groups II and III. The mean values (SEM) were 2.3 (0.29), 4.7 (0.59), and 5.3 (0.68), respectively. The conclusions from our study are: In a toothbrushing population using fluoride dentifrices and fluoridated drinking water, the oral hygiene training program with behavioral modification significantly reduced caries incidence on approximal surfaces. Frequent repetition of training in meticulous oral hygiene is almost redundant. PMID- 7865088 TI - Control of specific plaque bacteria. AB - The Specific Plaque Hypothesis posits that particular bacteria are of unique importance in the etiology of dental caries and periodontal diseases, and a logical conclusion is that these bacteria should be the targets for our 'magic bullets' in devising plaque-control methods. This paper considers the development of preventive measures based on understanding of the significance of particular bacterial species and the properties of those bacteria. Knowledge of the importance of specific organisms as mediators of disease and molecular studies on the properties of potential virulence factors may reveal potential targets for inhibition, blocking by synthetic analogues, or functional inactivation by antibodies. PMID- 7865089 TI - Mouthrinses. AB - Mouthrinses have been used for centuries for medicinal and cosmetic purposes, but it is only in recent years that the rationale behind the use of the ingredients has been subject to scientific research and clinical trials. Although Listerine held its position for many years in the vanguard of the anti-plaque agents, the advent of mouthrinses containing chlorhexidine was a major breakthrough in the research for a chemical means to prevent disease. Since that time, and especially in the past ten years, the number of formulations that claim to have anti-plaque, anti-calculus, and anti-caries activity has increased, and much emphasis has been placed on such substances as an adjunct to, or indeed to replace, conventional toothbrushing techniques. This review covers the literature on mouthrinses over the past five years, concentrating more on the anti-plaque, anti-gingivitis, and anti-calculus formulations. In the first section, the methods of conducting clinical trials of mouthrinses are discussed, and a plea is made for a greater degree of standardization of methodology with agreed acceptable levels of clinical benefit. Trials of established mouthrinses are considered, and the advantages and disadvantages of several newer formulations discussed. From the review, it appears that chlorhexidine has no equal in its effects on reduction of plaque and gingivitis, but major drawbacks lie in the taste and stain-producing problems. The pre-brushing rinse, Plax, does not have unqualified success in all trials, though the more recent European formulation may have promise. Newer rinses which inhibit bacterial adhesion to tooth surfaces also appear promising, and it is suggested that more work on combinations of active ingredients is necessary. PMID- 7865090 TI - Experiments with triclosan-containing mouthrinses: dose response--and an attempt to locate the receptor site(s) of triclosan in the mouth. AB - A double-blind cross-over clinical study was performed on eight volunteers to determine the plaque-inhibiting effect of different triclosan- and sodium lauryl sulfate (SLS)-containing mouthrinses. An attempt was also made to locate the binding site(s) of triclosan in the oral cavity. After the volunteers rinsed for four days with solutions of various concentrations of triclosan and/or SLS, plaque deposits were scored according to the Silness and Loe Plaque Index. The study showed that 0.15% and 0.3% concentrations of triclosan yielded a comparable plaque-inhibiting effect in vivo. Furthermore, the 0.1% triclosan with 1.5% SLS exhibited a higher (though not significant) effect than 0.1% triclosan with 0.75% SLS. The mouthrinse containing 0.05% triclosan and 0.25% SLS was as effective as the two mentioned mouthrinses containing 0.1% triclosan. Collectively, the results indicate that triclosan alone has an antiplaque effect, independent of the effect of SLS. Furthermore, the results suggest that the SLS monomers may play a role as carriers of triclosan and that the teeth are not the only binding site of triclosan, since topical application of 0.3% triclosan failed to produce a clinically discernible effect. PMID- 7865091 TI - Calculus formation and inhibition. AB - The formation, development, and dissolution of hard deposits such as calculus are complex processes that involve numerous calcium phosphate phases as well as the interaction of these ions with organic molecules. Although formation is determined by thermodynamic driving forces, kinetic factors are also important determinants for the precipitation of specific calcium phosphate phases. The overall process, therefore, may involve the formation of metastable intermediates which may subsequently transform into the more stable hard deposits observed in vivo. A knowledge of the kinetics of growth of both individual calcium phosphate phases and their mixtures is important for elucidating the mechanism of calculus formation. Although salivary proteins are effective inhibitors of the mineralization reactions that take place in dental plaque, once adsorbed, their conformation may change to present surfaces that catalyze the nucleation of mineral phases. The variable pH conditions in plaque, expressed in terms of free ionic concentrations, will markedly alter the supersaturations with respect to typical calcium phosphate precursor phases such as dicalcium phosphate dihydrate (DCPD) and octacalcium phosphate (OCP). Physical-chemical studies have shown that the mineralization of all the calcium phosphate phases is controlled by reactions at the surface rather than by diffusion of lattice ions through the contacting liquid phase. This makes the rates of reaction very sensitive to ions and molecules in the solution that may absorb at the active growth sites and, while not significantly incorporating into the precipitated crystal phases, markedly influences the rates of mineralization and demineralization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865092 TI - Connective tissue degradation in health and periodontal disease and the roles of matrix metalloproteinases and their natural inhibitors. AB - Connective tissue remodeling is essential for normal growth and development, and many diseases have long been associated with the breakdown of the collagenous matrix of bone, cartilage, and related tissues. Recent work has established that members of the family of matrix metalloproteinases (MMPs) are key enzymes in matrix degradation. They function at neutral pH and can digest synergistically all the matrix macromolecules. Biochemical and cloning studies indicate that there are three major groups, collagenases, gelatinases, and stromelysins. Naturally occurring inhibitors, TIMPs (Tissue Inhibitors of MetalloProteinases), are important controlling factors in the actions of MMPs, and tissue destruction in disease processes often correlates with an imbalance of MMPs over TIMPs. The major inhibitor is TIMP-1 (or TIMP), a 30-kDa glycoprotein that is synthesized by most cells. The expression of MMPs and TIMPs by cells is regulated by many cytokines (particularly interleukin-1, IL-1), growth factors, and hormones, some of which are specific to cell type and others that are ubiquitous (e.g., transforming growth factor beta, TGF-beta). One way in which pathogenic organisms might mediate tissue degradation in periodontal diseases is through the ability of cell wall antigens to stimulate cytokine production by circulating mononuclear cells. These would then induce MMP synthesis by resident gingival cells, thereby initiating degradative events. Direct in vivo evidence for the source of collagenase and other MMPs in periodontal tissues is limited. By using specific polyclonal antibodies and indirect immunofluorescence, we could demonstrate the presence of collagenase, stromelysin-1, gelatinase A, and TIMP in human gingival biopsy specimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865093 TI - Pathogenic mechanisms in periodontal disease. AB - Periodontal diseases have been considered as "infections" in which micro organisms initiate and maintain the destructive inflammatory response. Host mediated tissue destruction occurs via complement activation and the release of lysosomal enzymes, and connective tissue matrix metalloproteinases. Microbial enzymes may damage connective tissues directly, and, together with toxic metabolites and structural materials, are thought to disrupt the reparative activities of fibroblasts and cells of the immune defenses. The significance and relative contributions of host and microbial factors to the disease process remain unresolved. Environmental changes in the gingival sulcus and periodontal pocket and tissues, the degree of the host response and nutrient availability, concomitant with disease progression, compromise tissue metabolism and repair, and allow for enhanced or de novo expression of microbial virulence factors, such as proteases, which alter microbial pathogenicity. Proteolytic destruction of specific antibodies and complement by both viable and non-viable bacterial cells may retard phagocytic killing and removal of pathogens, thus prolonging the inflammatory response. Bacterial products may indirectly mediate tissue destruction by stimulating release of matrix metalloproteinases or by proteolytically inactivating the specific inhibitors of these enzymes. PMID- 7865094 TI - Gingival crevicular fluid: biomarkers of periodontal tissue activity. AB - The lack of precise clinical criteria for assessment of periodontal disease has led to a search for alternative means of determining active disease sites, prognosis of future sites of breakdown, and response to therapy. This review highlights the potential array of biomarkers present in gingival crevicular fluid and which may relate to existing or predicted tissue regions undergoing metabolic change and derived from bacterial or host-cell-derived products. Among the former may be listed endotoxin, amines, butyrate, and a variety of enzymes and their inhibitors, such as trypsin-like proteases and bacterial collagenase. Arising from host cells is a variety of leucocytic hydrolase enzymes, lactoferrin, and lysozyme. These appear to be useful inflammatory markers and may be distinguished from products of connective tissue breakdown which include collagenous and non collagenous products, including collagen peptides, osteonectin, and fibronectin. The proteoglycans have found particular favor as biomarkers of possible bone resorptive activity. Attention has also been directed at the immune response, including comment on immunoglobulins, complement, eicosanoids, and cytokines. This review lists available information on the presence of these in gingival sulcus fluid and wherever possible relates their presence to disease activity. PMID- 7865095 TI - Preventive therapy for periodontal diseases. AB - Rational approaches to the prevention of destructive periodontitis should be based on a clear understanding of etiology and pathogenesis. However, we are dealing with a heterogeneous family of diseases in which different factors operate. It is an oversimplification to regard poor oral hygiene, and hence an accumulation of non-specific dental bacterial plaque, as the major risk factor. Epidemiological evidence indicates that host factors are likely to be of overriding importance for the most severe forms. The limitations of nonspecific plaque control are therefore discussed. Specific inhibitors of virulence factors provide a logical approach, but their clinical application awaits improved knowledge. Improvement of general health and resistance to disease by proper nutrition, the avoidance of intercurrent disease, and elimination of smoking and stress-induced risk are encouraged. The genetic basis of susceptibility to periodontitis is increasingly understood, and, while gene therapy is not likely to be a practicable approach to prevention, genetic markers of risk are emerging. PMID- 7865096 TI - Synaptosomal T3 content in cerebral cortex of adult rat in different thyroidal states. AB - The quantitation of thyroid hormone levels in cerebrocortical synaptosomes of the adult rat at altered thyroid states was studied because of the recent idea of the involvement of thyroid hormone in the adult mammalian brain. In contrast to a marked fall in serum T3 levels in PTU-induced hypothyroid rats, the synaptosomal T3 content was raised by 9.5 fold in this hypothyroid situation compared to the euthyroid control rats. A single injection of T3 (2 micrograms/g) to the hypothyroid rats lowered the T3 level to about half of those values obtained in only hypothyroid condition. The T4 levels remained below the detectable range in all the groups tested. This may be because 70% to 80% of the intraneuronal T3 comes through the local deiodination of T4. The present investigation indicates a tendency for synaptosomal reorientation of T3 level for vital neurophysiologic function in altered thyroid conditions. PMID- 7865097 TI - Neurons expressing 5-HT2 receptors in the rat brain: neurochemical identification of cell types by immunocytochemistry. AB - The serotonin2 (5-HT2) receptor has been implicated in a number of behavioral and physiological processes. It may also play a role in cellular development and differentiation, and represents a site of action of hallucinogens and certain psychotherapeutic drugs. To better understand the functions and regulation of the 5-HT2 receptor, we have undertaken a series of studies in which we attempted to identify the specific cell types that express the receptor. This was accomplished using a variety of double-labeling strategies with an antibody we raised against the rat 5-HT2 receptor protein. In this review, we recount of some of our previously published findings and present some new data in which we identify subpopulations of cholinergic neurons in the brainstem and gamma-aminobutynic acid (GABA)ergic interneurons in the cortex that express 5-HT2 receptor immunoreactivity. Developmentally, the appearance of 5-HT2 receptor immunoreactivity occurs relatively late in teh ontogeny of the cells in which it is expressed, mostly in the early postnatal period. This argues against a significant role for this receptor in early development, though it may participate in some aspect of terminal differentiation. We discuss the significance of the cell-type-specific and temporal expression of the 5-HT2 receptor in the context of current hypotheses of neuropsychiatric disorders such as schizophrenia. PMID- 7865098 TI - Phencyclidine- and dizocilpine-induced hyperlocomotion are differentially mediated. AB - The dopamine (DA) D2 agonist quinpirole and the D2 receptor antagonists, haloperidol, raclopride, and remoxipride, were examined for their ability to block the locomotion induced by the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists phencyclidine (PCP) and dizocilpine, both given in equipotent doses. Quinpirole, given in a "DA D2 autoreceptor selective" dose (0.01 mg/kg), failed to influence the motor stimulation by PCP. On the other hand, the locomotor response induced by dizocilpine was significantly reduced by quinpirole. The three DA receptor antagonists blocked dose dependently the motor stimulation produced by both the low (2 mg/kg) and the high dose (3 mg/kg) of PCP. Haloperidol and remoxipride also blocked dose dependently and fully the stimulation produced by the low dose (0.1 mg/kg) of dizocilpine, whereas raclopride partially reduced the effect. The motor stimulation produced by the high doses of dizocilpine (0.2 mg/kg) and PCP (3 mg/kg) was reduced by haloperidol and raclopride only in cataleptogenic doses. Remoxipride, in contrast, fully blocked the effects of both PCP (3 mg/kg) and dizocilpine (0.2 mg/kg) in noncataleptogenic doses. These data suggest that different mechanisms of action may account for the motor stimulatory effects of PCP and dizocilpine. At the presynaptic level, PCP and dizocilpine may differ in the way they act on "regulatory" NMDA receptors controlling neuronal activity in midbrain neurons, and at the postsynaptic level they may interact with subtypes of NMDA receptors differentially coupled to subpopulations of D2 receptors. PMID- 7865099 TI - Anti-stress action of a corticotropin-releasing factor antagonist on behavioral reactivity to stressors of varying type and intensity. AB - Central administration of a Corticotropin-Releasing Factor (CRF) antagonist is well documented to attenuate a variety of behavioral responses to several distinct stressors; however, it is not yet clear whether the activation of CRF neurons is dependent on the type or intensity of the experimental stressor, or rather on the particular behavioral response to stress under study. To test the generality of the stress-protective effect of the CRF antagonist, alpha-helical CRF9-41, (1, 5 or 25 micrograms intracerebroventricularly), the present experiments employed a sensitive index of anxiogenic-like behavior by measuring suppression in exploration on the elevated plus-maze following exposure to social, swim, or restraint stressors. A 1 but not 5 or 25 micrograms dose of the CRF antagonist administered just prior to social, swim, or restraint stress reversed the stress-induced inhibition of exploratory behavior. Chlordiazepoxide and the steroid anesthetic, alphaxalone, also attenuated the anxiogenic-like effect of restraint stress and elevated the baseline exploratory behavior of nonstressed control groups. Although the stressors produced a graded secretion of adrenocorticotropin (ACTH) with the ranking restraint > swim > social, the relative amplitude of behavioral reactivity to social, swim, and restraint stress was comparable. The relative efficacy of the CRF antagonist to reverse the stressor effects was also comparable. These results suggest that antagonism of activated brain CRF systems attenuates the behavioral response to stress regardless of the type or intensity of the stressor as measured by ACTH secretion. PMID- 7865101 TI - Preexposure to, but not cotreatment with, the neurotensin antagonist SR 48692 delays the development of cocaine sensitization. AB - This study examined the role of neurotensin (NT) in the development of cocaine sensitization using the novel nonpeptide NT antagonist SR 48692. Male Sprague Dawley rats received five daily administrations of SR 48692 (80 micrograms/kg, IP or PO) or vehicle. Following a 7 day drug-free period, cocaine-induced (15 mg/kg, IP) locomotor activity was assessed. Subsequent cocaine tests occurred every other day. No differences were observed between groups during the first day of cocaine testing. Sensitization to the locomotor activating effects of cocaine occurred rapidly in the controls reaching peak effects by the third cocaine challenge injection. By contrast, subjects preexposed to SR 48692 IP were delayed in the development of cocaine sensitization maintaining significantly lower cocaine-induced activity counts relative to controls until the sixth cocaine challenge injection. Preexposure to SR 48692 PO also produced an attenuating effect on the development of cocaine sensitization. The decreased cocaine-induced activity in SR 48692-preexposed subjects did not appear to be the result of a locomotor deficit as SR 48692-preexposed subjects exhibited increased activity rates following a high dose (30 mg/kg, IP) cocaine challenge injection. In an additional experiment, the effect of cotreatment with SR 48692 on the development of cocaine sensitization was assessed. Subjects were cotreated with SR 48692 (80 micrograms/kg, IP) or vehicle 60 minutes prior to each of two cocaine (15 mg/kg, IP) or saline preexposure injections. Following a drug-free day, subjects were tested for cocaine-induced (15 mg/kg, IP) locomotor activation. SR 48692 cotreatment had no effect on the development of sensitization to cocaine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865100 TI - Genetic association between dopamine transporter protein alleles and cocaine induced paranoia. AB - Paranoia in the context of cocaine abuse is common and potentially dangerous. Several lines of evidence suggest that this phenomenon may be related to function of the dopamine transporter protein (DAT). DAT is the site of presynaptic reuptake of dopamine, an event that terminates its synaptic activity. The gene coding for dopamine transporter protein (DAT1) contains a variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region that can be typed by the polymerase chain reaction (PCR) (Vandenbergh et al. 1992). Although this is not a coding region polymorphism, it is close to the coding region and could plausibly be in linkage disequilibrium with a mutation in the gene. Cocaine blocks the dopamine transporter and increases synaptic availability of dopamine. We examined DAT alleles in 58 white and 45 black cocaine users in order to test only two hypotheses: (1) Is there an allelic association between DAT and cocaine dependence? and (2) Is there an allelic association between DAT and cocaine induced paranoia? We did not demonstrate an allelic association with cocaine dependence. However, within the white sample, DAT genotype was associated with cocaine-induced paranoia (allele frequency for allele 9 = .16 for those without paranoid experiences versus .35 for those with, chi 2 = 3.9 [2 x 2 table], p < .05). There was no significant difference for the same measure in the black sample. Certain DAT genotypes may therefore predispose to paranoia in the context of cocaine use in white populations. We caution that these results require independent replication. PMID- 7865102 TI - Vasoconstrictor effect of cyclosporin on the mesenteric artery in the dog. AB - To evaluate the effect of cyclosporin (CyA) on the mesenteric arterial bed, studies were performed on the isolated mesenteric artery perfused at a constant flow in 20 dogs. Changes in mesenteric perfusion pressure reflected variations in vascular resistance. Pure powder CyA was dissolved in autologous blood and injected at doses of 5, 10, 20 and 40 mg. Infusions of 5 and 10 mg CyA caused nonsignificant mean increases of 3 +/- 2 mm Hg [95% confidence interval (CI) -2 to +7; P > 0.05] and 3 +/- 3 mm Hg (95% CI -3 to +9; P > 0.05) in mesenteric perfusion pressure, with CyA blood levels in the mesenteric vein averaging 466 +/ 153 and 692 +/- 130 nmol/l, respectively, at the end of the injections. Infusions of 20 and 40 mg CyA caused significant increases in mesenteric perfusion pressure averaging 11 +/- 3 mm Hg (95% CI 3-18; P < 0.05) and 26 +/- 4 mm Hg (95% CI 16-34; P < 0.05), respectively. CyA blood levels at the end of infusion averaged 806 +/- 85 and 1118 +/- 89 nmol/l, respectively, in the mesenteric vein. Blockade of alpha-adrenergic receptors with phentolamine abolished the CyA vasoconstriction of the mesenteric artery, with the increase in perfusion pressure averaging 16 +/- 4 mm Hg before and 3 +/- 3 mm Hg after phentolamine (P < 0.05). Thus, in the dog, CyA causes an acute vasoconstriction of the mesenteric artery through stimulation of alpha-adrenergic receptors. PMID- 7865103 TI - MC 1288--a vitamin D analogue with immunosuppressive effects on heart and small bowel grafts. AB - The vitamin D analogue MC 1288 (20-epi-1 alpha,25-dihydroxycholecalciferol) was tested here for its possible immunosuppressive properties in vivo using different rat transplantation models. MC 1288, in a dose of 0.1 microgram/kg daily, administered intraperitoneally for 10 days, was found to be effective in prolonging cardiac allograft survival. Untreated recipients rejected their grafts around day 8 while MC 1288 treatment delayed rejection until day 22 (P < 0.001). Addition of the immunostimulatory drug LS-2616 (Linomide) reduced the immunosuppressive effect of MC 1288 and rejection occurred around day 11. The immunosuppressive effect of MC 1288 on rejection following small bowel transplantation was determined by measuring the amounts of hyaluronan (HA) secreted into the intestinal lumen. On day 6 post-transplantation the amounts of intraluminal HA in untreated animals was 29.2 +/- 5.3 ng/min and cm, while in MC 1288-treated animals it was just 5.0 +/- 1.6 ng/min and cm (P < 0.01). We conclude that MC 1288 has immunosuppressive effects that may make it suitable for the prevention of graft rejection. PMID- 7865104 TI - A new method for rat accessory hepatic transplantation--the cervical approach. AB - Current methods for accessory liver transplantation in the rat require a high degree of microsurgical expertise and long training before success is achieved. We present a simpler method of arterialized accessory liver transplantation using the cervical vessels for revascularization of the transplanted liver with the cuff technique, which is useful for studies of liver preservation, reperfusion injury, and liver regeneration. After classical 70% hepatectomy is performed on the graft, the right common carotid artery is anastomosed to the donor aorta, the distal right external jugular vein is anastomosed to the donor portal vein, and the proximal right external jugular vein is anastomosed to the donor supradiaphragmatic inferior vena cava. The skin is not closed over the cervically transplanted liver (CTL). This method was used 30 times for periods of up to 6 h with a 90% success rate. CTL structure and function, as revealed by histology, bile flow rates, biliary bilirubin concentrating capacity, membrane potential, enzyme activity and distribution, have shown the CTL to be a structurally normal and metabolically active graft. In conclusion, the cervical approach to arterialized accessory liver transplantation is simple, and should prove useful for studies of liver preservation, reperfusion, regeneration, physiology, and toxicology. PMID- 7865105 TI - Transmission of donor lymphocytes in clinical lung transplantation. AB - Passenger mononuclear cells in organ grafts are known to influence the alloimmune response to the graft. To assess their relevance in clinical lung transplantation, we studied the amount, distribution, cell types, and surface marker expression of mononuclear cells in human donor lungs. Two major compartments of mononuclear cells could be differentiated: lymph nodes containing resting T and B lymphocytes, and the lung tissue itself, containing mainly activated lymphocytes as well as monocytes/macrophages. Tissue-associated mononuclear cells make up 20-40 x 10(9) cells per lung, about 30-50% of which are lymphocytes. Tissue-associated lymphocytes are predominantly T and NK cells; most of the T cells are CD8+ CD45R0+ and express HLA-DR. Strong expression of the adhesion molecules LFA-1 and ICAM-1 is present on infiltrating cells as well as on resident cells of the organ. Moreover, the lymphocytes inside the lung tissue are functionally highly active, with a strong stimulatory as well as alloreactive potency. Thus, large numbers of allogeneic mononuclear cells and particularly large numbers of functionally active lymphocytes are obviously transmitted by human lung allografts. The immunological in vivo relevance of these cells after lung transplantation may include allostimulation and graft-versus-host activity, but also beneficial immunomodulatory effects. PMID- 7865106 TI - Clinical significance of in vitro donor-specific hyporesponsiveness in renal allograft recipients as demonstrated by the MLR. AB - A longitudinal study was carried out on 19 recipients of cadaveric renal allografts, monitoring their anti-donor and anti-third party responses in the mixed lymphocyte reaction (MLR) at the time of transplantation and at 3, 6, and 12 months post-transplant. Two patterns of responses were identified: in the first (n = 11), patients showed, or later developed, donor-specific hyporesponsiveness, and in the second (n = 8), patients had persistent antidonor and anti-third party responses. After 1 year, the serum creatinine, number of episodes of acute rejection and biopsy findings were compared in both groups. In the first group, the mean serum creatinine was 136.4 mmol/l, the total number of acute rejection episodes was three and in nine of the ten available biopsies, there were minimal cellular infiltrates and normal appearance of the glomeruli, tubules and blood vessels. In the second group, the mean serum creatinine was 163 mmol/l, the total number of acute rejection episodes was 12 and in five of the seven biopsies available, evidence of ongoing rejection was obtained. The difference in mean serum creatinine was not statistically significant (P > 0.05), but the difference in the numbers of acute rejection episodes was (P < 0.05). It is concluded that in some renal allograft recipients, a state of donor-specific hyporesponsiveness develops, and this state may be associated with better graft outcome at 1 year. These data may be useful in selecting patients for reduced immunosuppressive therapy. PMID- 7865107 TI - Clinical evaluation in organ transplant patients of a polymerase chain reaction test for CMV DNA applied on white blood cells and serum. AB - A polymerase chain reaction (PCR) test for CMV DNA was evaluated for clinical usefulness. Leukocytes and serum were sampled from 36 patients who had recently undergone organ transplantation. Clinical symptoms, virus culture, and IgG and IgM antibodies were used to identify, in retrospect, patients with CMV disease certified beyond all doubt, with probable disease, with asymptomatic infection, or without infection. PCR tests for CMV DNA in leukocytes (BC-PCR) and serum (SE PCR) were then evaluated. BC-PCR was positive in all patients with certified CMV disease but also in 31% of the samples from patients without infection. SE-PCR was positive in 11/13 patients with certified disease and was concordant with CMV culture in 192/231 tests. Of the 39 discordant cases, 27 had a positive SE-PCR with a negative culture. The effect of ganciclovir treatment could not be predicted by any test. In conclusion, a negative BC-PCR is strong evidence against CMV disease and a positive SE-PCR strongly suggests CMV disease, but the opposite results are of little clinical help. PMID- 7865108 TI - Hepatic artery interruption followed by portal vein thrombosis in an adult liver transplant. AB - Vascular complications following liver transplantation result in significant morbidity and mortality. We report a 28-year-old man who, because of a mycotic false aneurysm, underwent ligation of the hepatic artery 4.5 weeks post transplantation and who, 4.5 months later, suffered a portal-mesenteric vein thrombosis. Adverse hepatic sequelae did not follow these events, demonstrating the capacity of the collateral circulation to perfuse the transplanted liver. PMID- 7865109 TI - Cyclosporin A in fat emulsion carriers: studies on the immunosuppressive potential, using the heterotopic heart transplant model in rats. AB - Cyclosporin A (CyA) is an extremely lipophilic drug that needs a solubilizing agent to become soluble in water. In the commercially available intravenous formulation--Sandimmun--Cremophor EL is used for this purpose. It is likely that Cremophor EL contributes to some of the side effects produced by i.v. Sandimmun. We have recently shown that if Cremophor EL is replaced by a soybean oil (SBO) based fat emulsion carrier, the acute renal side effects following i.v. administration of CyA are avoided in a rat model. It is then important to ascertain whether the use of a fat emulsion carrier alters the immunosuppressive effect of CyA. Moreover, fatty acids can themselves influence the immune system, and both omega-3 and omega-6 fatty acids have been reported to possess immunosuppressive properties. In the present study, the effect on graft survival of i.v. CyA administered in five different formulations, using fat emulsions or liposomes as carriers, was compared to that of conventional Sandimmun infusion substance in the heterotopic heart transplant model in rats. The new formulations tested did not reduce the immunosuppressive effect of CyA. On the contrary, a small but significant increase in graft survival was noted in the groups given CyA in the SBO-based fat emulsion carrier (17.0 +/- 0.82 days) and CyA in liposomes (16.0 +/- 0.63 days) as compared to the results in the Sandimmun treated group (15.0 +/- 0.58 days: P < 0.01 and P < 0.05, respectively). PMID- 7865110 TI - Chronic rejection of liver transplants revisited. AB - We examined 27 hepatectomy specimens to assess the frequency of foam cell endovasculitis and bile duct loss in chronic rejection. Arterial lesions, defined as total occlusion by subintimal foam cells and/or fibromuscular proliferation, were found mainly in hilar and septal arteries, whereas bile duct loss, defined as the absence of bile ducts in more than 50% of portal tracts, affected mainly small tracts. Both were found in 20 livers (74%). In two livers (7%) there was significant bile duct loss but no arterial lesions, whilst in five cases (19%) there were occlusive arterial lesions but no bile duct loss. Small arteries were involved in only 10% of the cases. These results indicate that in one-third of the cases arterial and bile duct lesions develop independently of each other, suggesting different pathogenetic pathways. In addition, liver biopsy may not be pathognomonic since small arteries are involved in only 10% of cases and bile duct loss may not be extensive. In such cases the diagnosis of chronic rejection should only be made in the presence of progressive clinical deterioration. PMID- 7865111 TI - Acute abdominal pain after vesical catheterization in a kidney and pancreas graft recipient. PMID- 7865112 TI - Bilateral renal cell carcinoma and kidney transplantation--how long should we wait? PMID- 7865113 TI - [Importance of epicutaneous tests in drug allergy]. AB - Epicutaneous tests do not permit resolution of all the problems set by drug allergy, but they are an important asset. Their value is sure when the pathology does not correspond precisely with a Gell and Coombes hypersensitisation classification, and especially when there is an interaction between several mechanisms. This presentation of five cases shows the value of these tests. PMID- 7865114 TI - Sensitivity to olea Europaea pollen in different populations in Israel. AB - Sensitivity to olive pollen was studied (by skin tests) in different Israeli populations suffering from respiratory allergies. The results were compared with aerobiological data, in order to correlate amount of exposure to prevalence of sensitization. It was found that in the Jewish population, sensitivity to olive pollen developed in direct proportion with the number of olive trees in the settlement: 66% where trees density is high, 29% where it is low. In the Arab population however, possibly genetically determined, the sensitization to olive pollen was low (only 14%) even though the density of trees is high. PMID- 7865115 TI - [Allergy to olive trees and Oleaceae in the south of France]. AB - In France, olive is widespread only around the Mediterranean; 35,000 hectares are cultivated for a total of 3,500,000 trees. Pollen counts for 1993 showed a low pollinisation of olive: 60 pollen grains/m3 at Toulouse in a total of 29,972 pollens, 355 at Perpignan (total 56,323), 1138 at Montpellier (total 98,821), 515 at Nimes (total 57,836), 810 at Marseille (total 143,497) and 976 at Nice (total 8,890). The other Oleaceae are represented by Fraxinus, which is very abundant at Montpellier with 1,147, Ligustrum which was found at Perpignan with 159 and also Phillyrea in the Montpellier region. A recent study by Mrs Rovira, made on the dossiers of consultants from the Service d'Allergologie of Ste Marguerite Hospital at Marseille (D. Vervloet), with all families taken together, found that Olive caused about 1/3 positives of grasses. PMID- 7865116 TI - [Contact allergy to sulfites: contact allergens, sources of exposure, and clinical profile]. AB - Contact allergy to sulphites has been discovered recently. This study considers the data necessary to make an accurate clinical profile that gives the possibility of such sensitization. Exposure sources are recalled to suggest avoidance by affected patients. PMID- 7865117 TI - [Hymenopteran venom allergy in 1994]. PMID- 7865118 TI - [Targetted antibiotic therapy. Acute sore throat: streptococcus A update]. AB - Acute sore throat is a very common pathology, but should not because of this be considered as banal. In effect, the beta-haemolytic streptococcus A, which is responsible for most of the bacteriological etiologies is not only responsible for distant inflammatory complications, acute articular rheumatism (RAA) and glomerulonephritis, which are re-appearing in the United States, but also a fulminating septicemia and a syndrome of visceral failure that makes a grave prognosis for life. Moreover, today, streptococcus A is one of the factors involved in a series of fatal fasciites and necrosing myosites seen in several European countries. Understanding of these complications gives better definition of the causative immunological mechanisms and particularly the adverse role of the "superantigens" of streptococci in the start of an increase in the responses of immunocompetent cells and pro-inflammatory and prothrombic mediators. Finally, availability now of rapid diagnostic tests with monoclonal antibody techniques confirms the presence of streptococci A in acute sore throat and should help the physician to make an etiological diagnosis that takes into account the clinical signs. Unfortunately, these tests are not widely available in France and are not subject to reimbursement. All these factors justify the introduction of an antibiotherapy targetted at streptococcus A in the context of bacterial sore throat. Oral penicillin V (phenoxymethyl penicillin, Oracilline) is always the reference, with an excellent anti-bacterial and clinical activity and without risk of production of strains of streptococcus that are of reduced sensitivity or resistant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865119 TI - [Therapeutic strategy for sore throat: current role for targetted antibiotic therapy]. AB - The beta-haemolytic streptococcus A, which is responsible for almost all bacterial sore throats in children and young adults, is the target for the first antibiotic treatment. What is really at stake for the treatment is to prevent the serious complications linked with this germ, acute articular rheumatism (RAA) and glomerulonephritis. The recurrence of RAA seen in the United States from 1985, has started many investigations as much for epidemiology as for therapy. Some authors have questioned the treatment with penicillin because of the rise in numbers of carriers of streptococcus A after treatment. They have suggested the use of compounds with a greater spectrum of activity. However, work in the international literature re-states the benefits of a targetted antibio-therapy in this context. Is it appropriate to use a wide spectrum antibiotic to treat an infection of monobacterial target, taking into account the bacteriological and clinical efficacy of penicillin, the only available treatment that has shown its capacity to prevent RAA, with a treatment length of 10 days and which seems to be constant with time? Because of this, faced with the ecological risks of a multi use of wide range compounds, with a treatment that has not been validated in France, phenoxymethylpenicillin, Oracilline, penicillin V, the antibiotic targetted to sore throat and the streptococcal risk, is correct now for 1994. PMID- 7865120 TI - [Choice of antibiotic therapy for acute streptococcus A sore throat: new bacteriologic data]. AB - The choice of antibiotic therapy for sore throat of bacterial origin must be directed against the beta-haemolytic streptococcus A, or more rarely C and G. Recent bacteriological data confirm the raised and constant antibacterial activity in vitro of penicillins V and G, with minimal inhibitory concentrations (CMI) as low as 0.01 mg/ml. Until now, there have been no resistant or reduced sensitivity strains reported. Those strains reported as "tolerant" to penicillin are not correlated with therapeutic checks. As for strains of "intermediate sensitivity" to penicillin, these should be attributed to effects of the diffusion techniques. In contrast, in France now, 8% of strains of streptococcus A are resistant to macrolides and 60% to tetracyclines. Finally, new data show that the different selective powers of beta-lactamines, especially cephalosporins, introduce risks of modification of the oro-pharingeal ecology, linked in part with transfer of genetic material between commensal streptococci of reduced sensitivity to beta-lactamines to sensitive pneumococci. All these data emphasize the importance of an antibiotic therapy that is directed to streptococcus A, with a strong and constant bactericidal activity, without risk of selection or appearance of strains of resistant streptococcus A, and that will not disturb the long term bacterial ecology of the oro-pharynx. Now, in 1994 phenoxymethylpenicillin, Oracilline, penicillin V has the place of reference in the treatment of bacterial acute sore throat. PMID- 7865121 TI - Protein crystal growth in microgravity. AB - Protein crystal growth is quite important for the determination of protein structures which are essential to the understanding of life at molecular level as well as to the development of molecular biotechnology. The microgravity environment of space is an ideal place to study the complicated protein crystallization and to grow good-quality protein crystals. A number of crystal growth experiments of 10 different proteins were carried out in August, 1992 on the Chinese re-entry satellite FSW-2 in space using a tube crystallization equipment made in China. A total of 25 samples from 6 proteins produced crystals, and the effects of microgravity on protein crystal growth were observed, especially for an acidic phospholipase A2 and henegg-white lysozyme which gave better crystals in space than earth-grown crystals in ground control experiments. The results have shown that the microgravity in space favors the improvement of the size, perfection, morphology and internal order of the grown protein crystals. PMID- 7865122 TI - Connection ensemble model of local neural circuits. AB - A connection ensemble model (CEM) of local neural circuits in central nervous system (CNS) is proposed in this work. Neuronal interactions are investigated at two levels, i.e. the synaptic connection between single neurons and the macro connections between different neuronal groups. The efficacy of macro-connection is quantitatively determined by the efficacies of constituent synapses, and is asymptotically stable. This model provides a reasonable description for the functional invariance of local neural circuits with structural diversities, which is a widely observed fact in neurobiology. It is expected that the works in CEM model would enrich the current research in neural dynamics. PMID- 7865123 TI - A new genetically engineered vaccine for animal growth promotion. AB - The chemically synthesized somatostatin (ss) gene was fused in phase with the 3' end of hepatitis B virus surface antigen (HBsAg) gene. The fusion gene HBs/ss was then recombined into the genome of vaccinia virus. This recombinant virus (vv HBs/ss) can express hybrid HBsAg/ss particles which present as determinants on their surfaces, thereby bearing a good immunogenicity. This new strategical vaccine of ss can elicit the production of antibody capable of neutralizing ss in the plasma, and consequently enhance the growth of animals. PMID- 7865124 TI - Mitochondrial DNA polymorphism in natural populations of Drosophila albomicans (I)--Remarkable mtDNA polymorphism in the population of D. albomicans. AB - The technique of mtDNA restriction fragments length polymorphism (RFLP) was used to survey the population structure of D. albomicans. Remarkable mtDNA polymorphism has been observed in D. albomicans populations. A total of 34 nucleomorphs were detected from 82 isofemale lines assayed by only 8 restriction enzymes. The cause and the effect of this phenomenon were discussed. As a result, it is suggested that a mechanism which maintains mtDNA diversity exists in this fly, and that the high intra-populational polymorphism could numerically conceal the extent of differentiation between populations. In addition, on the base of restriction maps, it was found that the mtDNA molecule of D. albomicans might be impacted by the selection pressure during its evolution process both on the nucleotide composition and on the functional regions. PMID- 7865125 TI - Correlation between unfolded states of apocytochrome c and its ability to pass lipid bilayer. AB - In contrast to the horse heart apocytochrome c, the chicken heart apocytochrome c underwent a conformational change from random coil to partial folding during a renaturation process. When the apocytochrome horse heart and that of chicken heart c were subjected to a translocation assay in vitro using large trypsin enclosed unilamellar vesicles from soybean phospholipids, the ability of the chicken heart apocytochrome c to penetrate into the liposomes was found to decrease markedly with the renaturation procedure, while that of horse heart apocytochrome c remained relatively constant. Observations from circular dichroism measurement on the induction of secondary folding of these two species of apocytochrome c upon interaction with soybean phospholipid vesicles suggested that a more flexible structure of apocytochrome c embedded in the lipid matrix be required for its efficient translocation across the bilayer. PMID- 7865126 TI - Treatment of beta-thalassemia with hydroxyurea (HU)--effects of HU on globin gene expression. AB - A newly developed method of RT-PCR/competitive PCR for measuring the relative and absolute content of globin mRNAs as well as micro-globin chain biosynthetic assay have been used to study the alterations of globin gene expressions in the patients with beta-thalassemia pre- and post-hydroxyurea (HU) treatment. It was found for the first time that HU had the effect of enhancing beta-globin gene expression in some patients. Two cases with beta-thalassemia who were subjected to HU treatment for over two years showed a marked increase in beta-globin mRNA level and beta-globin chain synthesis, resulting in more effective erythropoiesis and the alleviation of clinical symptoms. PMID- 7865127 TI - Identification of a 12.5-kD protein from caudate-putamen nucleus as a dopaminergic neuronotrophic factor. AB - The effect of the extract from caudate-putamen nucleus of newborn rats (CPe) on the dopaminergic (DA) neurons has been studied. An MTT colorimetric microassay measuring optical densities for the growth of DA neuron cultures reveals a significant increase in growth for cultures with CPe as compared to those without CPe (p < 0.05). Rhodamine retrograde-prelabelled DA neurons were cultured on a Phastgel containing all the electrophoretically separated protein bands from CPe, and able to fish out from it their own trophic factor, a 12.5-kD protein band. The survived neurons at the 12.5-kD protein band were immunostained positive with anti-dopamine antibody. Co-culturing the 12.5 kD-containing gel strip with explants from substantia nigra at a close distance for a week revealed anti dopamine immunopositive neurites outgrowing from the explants only towards the 12.5-kD gel strip. These results indicate that a 12.5-kD protein from the CPe is capable of maintaining the survival of DA neurons of the substantia nigra and promoting their neurite outgrowth. PMID- 7865128 TI - Identification of a cAMP-response element on the human proopiomelanocortin gene upstream promoter. AB - Proopiomelanocortin (POMC) is an example of a gene that is stimulated by cAMP without containing the classical cAMP-responsive element on its promoter. To characterize POMC sequences conferring cAMP responsiveness, we used mouse pituitary AtT-20 cells for transient expression of chloramphenicol acetyltransferase reporter gene constructs containing 5'-flanking sequences of the human POMC gene. A novel POMC-cAMP-responsive element (POMC-CRE) was identified, which is located between nucleotides -344 and -319 and which lacks the classical CRE core motif (CGTCA). Using gel retardation assays in combination with antibodies against CREB, we provided evidence that both AtT-20 cell derived and in vitro translated CREB proteins bind to the POMC-CRE and thus may be involved in the stimulation of the gene. PMID- 7865129 TI - The chicken transforming growth factor-beta 3 gene: genomic structure, transcriptional analysis, and chromosomal location. AB - In this paper, we report the isolation, characterization, and mapping of the chicken transforming growth factor-beta 3 (TGF-beta 3) gene. The gene contains seven exons and six introns spanning 16-kb of the chicken genome. A comparison of the 5'-flanking regions of human and chicken TGF-beta 3 genes reveals two regions of sequence conservation. The first contains ATF/CRE and TBP/TATA sequence motifs within an 87-bp region. The second is a 162-bp region with no known sequence motifs. Identification of transcription start sites using chicken RNA isolated from various embryonic and adult tissues reveals two sites of initiation, P1 and P2, which map to these two conserved regions. Comparison of 3'-flanking regions of chicken and mammalian TGF-beta 3 genes also revealed conserved sequences. The most significant homologies were found in the 3'-most end of the transcribed region. DNA sequence analysis of chicken TGF-beta 3 cDNAs isolated by 3'-RACE revealed multiple polyadenylation sites unusually distant from a poly(A) signal motif. A Msc I restriction fragment length polymorphism (RFLP) marker was used to map the TGFB3 locus to linkage group E7 on the East Lansing reference backcross. Linkage to the TH locus showed that the TGFB3 locus was physically located on chicken chromosome 5. PMID- 7865130 TI - Isolation of cDNA clones for 42 different Kruppel-related zinc finger proteins expressed in the human monoblast cell line U-937. AB - To study the complexity and structural characteristics of zinc finger proteins expressed during human hematopoiesis and to isolate novel regulators of blood cell development, a degenerate oligonucleotide probe specific for a consensus zinc finger peptide domain was used to isolate 63 cDNA clones for Kruppel-related zinc finger genes from the human monoblast cell line U-937. By extensive nucleotide sequence and Northern blot analysis, these cDNA clones were found to originate from approximately 42 different genes (HZF 1-42) of which only 8 have previously been described. Northern blot analysis showed that a majority of these genes were expressed at comparable levels in U-937 and HeLa cells. The large number of individual genes represented among the 63 clones and their apparent non cell-type-specific expression suggest that the majority of the Kruppel-related zinc finger genes are likely to be expressed in most human tissues. In contrast, some of the genes displayed a restricted expression pattern, indicating that they represent potential regulators of monocyte differentiation or proliferation. Detailed structural analysis of the first 12 cDNAs (HZF 1-10) and a partial characterization of HZF 11-42 revealed that a common feature of human Kruppel related zinc finger proteins is the presence of tandem arrays of zinc fingers ranging in number from 3 to over 20 that are preferentially located in the carboxy-terminal regions of the proteins. In addition, several novel KRAB containing zinc finger genes and a novel conserved sequence element were identified. PMID- 7865131 TI - Recent evolution of genes encoding the prohormone-like protein SMR1 in the rat submandibular gland. AB - The Variable Coding Sequence (VCS) multigene family of Rattus norvegicus, is composed of at least 10 members, and shows extensive evolutionary divergence in the protein-coding region. Three members of the VCSA subclass, have been characterized: one of them, the VCSA1 gene mainly expressed in the submandibular gland (SMG) encodes the prohormone-like protein, SMR1-VA1. As VCSA-related genes have not been detected in Mus musculus, the VCSA genes subclass is presumed to have recently emerged. To study the evolution of this subclass, we have looked for VCSA genes in a closely related species, Rattus rattus. By Northern analysis, we demonstrate that VCS-related mRNAs are present in the SMG, and that the level of VCSA mRNA accumulation is approximately equal in both sexes. By contrast, in R. norvegicus, males accumulate about 3,000 times more VCSA1 mRNA than females. Using total SMG mRNA, an almost full-length cDNA, homologous to the cDNA of the R. norvegicus VCSA1 gene, was cloned by reverse transcriptase polymerase chain reaction (RT-PCR). The putative corresponding SMR1-VA1 protein is 146 amino acids long and presents the features characteristic of a secreted protein, with a potential signal peptide of 22 amino acids in the amino-terminal portion. The presence of potential processing multibasic sites suggests that small peptides could be generated (particularly a hexapeptide: Arg-Gln-His-Asn-Leu-Arg), as in the case of the SMR1-VA1 protein of R. norvegicus. From Southern blot analysis there appears that species-species modifications of VCSA gene copy number have occurred; R. rattus contains a greater VCSA1 copy number than R. norvegicus (two or three and one, respectively). PMID- 7865132 TI - Molecular cloning, cDNA sequence, and localization of a prohormone convertase (PC2) from the Aplysia atrial gland. AB - Neuropeptides and peptide hormones are synthesized as part of larger precursor proteins that are processed post-translationally by subtilisin-related calcium dependent prohormone convertases (PCs), frequently at multiple basic sites, to generate biologically active peptides. The atrial gland of Aplysia californica produces large quantities of egg-laying hormone (ELH)-related peptides, providing a unique opportunity to study prohormone processing. We have screened an Aplysia atrial gland cDNA library using a Lymnaea stagnalis PC2 probe and have isolated an Aplysia PC2-related 4.6-kb cDNA partial clone that was truncated on the 5' end. The remaining 5' atrial gland PC2 nucleotide sequence was obtained by reverse transcription/polymerase chain reaction (RT-PCR). The composite cDNA structure (5.6 kb) was deduced from sequence analysis of the RT-PCR product combined with the sequence obtained from the cDNA clone. The deduced cDNA of Aplysia atrial gland PC2 encoded a putative preproendoprotease of 653 amino acids that was evolutionarily related to other eukaryotic PC2s, and showed the strongest sequence identity with recently reported Aplysia nervous tissue PC2 sequences. In situ hybridization demonstrated extensive expression of PC2 in atrial gland secretory cells. The cDNA clone contained a relatively long 3'untranslated region (3'-UTR) of 3,632 nucleotides. Strikingly, the 3'-UTR also contained several major nucleotide repeat sequences including the microsatellite repeats, (CA)n and (TG)n, and a TA-rich region comprised largely of the triplet repeat (TTA)n. The characterized Aplysia PC2 is a candidate endoprotease that may play an important role in the processing of ELH-related precursors in the atrial gland and represents the first example of PC2 expression in exocrine tissue. PMID- 7865133 TI - Coordinate expression of the PRM1, PRM2, and TNP2 multigene locus in human testis. AB - Maintenance of the transcriptionally inert state of the mature human spermatozoon requires the expression of the various members of the human protamine gene cluster prior to the final stages of spermatogenesis. During this process, known as spermiogenesis, round spermatids morphologically differentiate into mature spermatozoa. The expression of the PRM1, PRM2, and TNP2 genes facilitates the compaction and condensation of the genetic material within the developing spermatid. To understand better the coordinate control governing this transformation, we have examined the localization and distribution of the human protamines PRM1 and PRM2 and transition protein TNP2 transcripts during human spermatogenesis. The stage-specific expression of these transcripts was determined by in situ hybridization analysis using [alpha-35S]-labeled cRNA probes. PRM1, PRM2, and TNP2 transcripts were abundant in association with round and elongating spermatids, located in the adluminal region of the seminiferous epithelium. They were not observed in association with spermatogonia, spermatocytes, Sertoli cells, or interstitial cells. These data indicate that the human PRM1, PRM2, and TNP2 transcripts are expressed postmeiotically in round and elongating spermatids. The quantitative evaluation of each transcript was determined as a function of the relative optical density per unit area. In all cases examined, the relative level of each transcript was consistent with the following pattern, PRM2 > PRM1 congruent to TNP2. PMID- 7865134 TI - CYP52 (cytochrome P450alk) multigene family in Candida maltosa: identification and characterization of eight members. AB - Previously, we characterized three genes and presented evidence for an n-alkane inducible cytochrome P450 (P450alk) multigene family in an n-alkane-assimilating and diploid-type yeast, Candida maltosa. In the present report, we isolated and characterized additional members of this gene family, including a total of thirteen P450alk-related sequences (eight genes and five of their alleles). Two sets, each consisting of two genes, were tandemly arranged in the genome. A gene replacement experiment showed that at least one gene had only a single allele in the genome. The determined nucleotide and the deduced amino acid sequences indicated that all had a characteristic constituent for P450s and exhibited amino acid identities from 94% to 37% to each other. Six genes showed relatively higher similarities to each other than to the other two genes and were thus classified into a subfamily. All the members of this subfamily were assigned to the same single chromosome, showing a good correlation between sequence similarity and chromosomal linkage. Although all the genes except for one were induced by n alkane, their inducibilities by some other aliphatic carbon sources showed variabilities. PMID- 7865136 TI - Activation of the nuclear oncogenes N-myc and c-jun in carcinoid [correction of cartinoid] tumors of transgenic mice carrying the human adenovirus type 12 E1 region gene. AB - The adenovirus (Ad) E1 region genes, E1A and E1B, are well known cooperatively to transform primary rodent cells and activate a number of cellular promoters, including nuclear oncogenes such as N-myc and c-jun, in transfected cell lines. However, there is still less information available on the in vivo mechanism(s) by which the E1 region gene, when chromosomally integrated in the living animals, exerts its effect on nuclear oncogene activation coupled with transformation. To investigate such in vivo activity of E1A we have used a series of microinjection experiments into fertilized eggs to generate three transgenic mice carrying the Ad12-type E1A/E1B genes under the control of the human renin gene. This transgene caused an early onset of bowel cartinoid tumors that express neural cell adhesion molecules, but do not metastasize to any region. Northern blot analysis revealed that the transgenes were considerably expressed in the tumors, but not in other tissues at detectable levels. Interestingly, the levels of N-myc and c-jun mRNAs in the cartinoid tumors were elevated 19- and 8-fold, respectively, as compared with those found in the control intestine. In contrast, the major histocompatibility complex (MHC) class I mRNA level was not altered between the tumor and control intestines, suggesting that this unchanged expression may reflect the loss of tumor metastasis. These findings provide the first in vivo evidence that the expression of the Ad12 E1 region gene induces cartinoid tumors associated with the activation of the nuclear oncogenes N-myc and c-jun. PMID- 7865135 TI - Maintained PC1 and PC2 expression in the AtT-20 variant cell line 6T3 lacking regulated secretion and POMC: restored POMC expression and regulated secretion after cAMP treatment. AB - Two variant cell lines were recently established from parent AtT-20 cells. Whereas HYA.15.10.T.2 have a reduced level of secretory granules, HYA.15.6.T.3 are completely devoid of both the regulated pathway of secretion and of dense core secretory granules. AtT-20 cells normally express the processing enzymes PC1, PC2, furin, carboxypeptidase E, and peptidylglycine alpha-amidating monooxygenase, as well as proopiomelanocortin, chromogranin B, and 7B2. We measured the expression of these mRNAs in both variant cell lines. Although some differences in mRNA level were noted, HYA.15.10.T.2 and HYA.15.6.T.3 cell lines maintained their expression of the processing enzymes and of 7B2. Furthermore, PC1 and PC2 were shown to be functionally active in the HYA.15.6.T.3 cells. In contrast, proopiomelanocortin and chromogranin B mRNA levels were no longer detectable in HYA.15.6.T.3 cells. Interestingly, stimulation of the HYA.15.6.T.3 cells with cAMP restored proopiomelanocortin mRNA, beta-endorphin immunoreactivity, and dense-core granules. Furthermore, at the ultrastructural level, beta-lipotropin immunoreactivity was detected in granules of cAMP-induced HYA.15.6.T.3 cells. Finally, depolarization of cAMP-induced HYA.15.6.T.3 cells with 56 mM potassium chloride resulted in a marked increase in the release of beta-endorphin immunoreactivity. These observations demonstrate that cAMP restores the regulated pathway of secretion in HYA.15.6.T.3 cells, which under untreated conditions do not demonstrate regulated release. These variant cell lines are unique models to understand better the relationship of the regulated pathway and the expression of the processing enzymes. PMID- 7865137 TI - Mucins in normal and neoplastic human gastrointestinal tissues. PMID- 7865138 TI - Diagnosis and surgical treatment of cervical cancer. PMID- 7865139 TI - Treatment of alcoholism as a chronic disorder. AB - Alcoholism is a common disorder that tends to be chronic and relapsing. Although there is clear evidence that treatment can be expected to induce a period of remission or at least decreased symptoms, treatment of alcoholism is generally regarded as unsuccessful. Alcoholism should be approached as a chronic medical disorder such as diabetes or arthritis. Complete abstinence is the preferred goal, but "cures" or permanent abstinence from alcohol are rare. In this model, treatment benefits may be measured by length of remission, reduction in alcohol use, improvement in health and enhancement of social functioning. Treatment continues over a period of years, mainly on an outpatient basis with increasing intensity if symptoms recur. Medications that reduce craving for alcohol or diminish the euphoric effects of alcohol would be very helpful in the management of this chronic disorder. Preclinical studies have produced evidence for involvement of the endogenous opioid system in the reinforcing effects of alcohol. Recent controlled clinical trials of the opiate receptor antagonist naltrexone suggest that medications of this type may improve the results of treatment for alcoholism. PMID- 7865140 TI - New drugs for the treatment of experimental alcoholism. AB - This article presents a current overview of the efforts to suppress pharmacologically the craving, dependence, or other factors associated with the self-selection of alcohol in an experimental animal. The contemporary status of the pharmacotherapy of experimental alcoholism similarly is described for different animal models of alcohol drinking. An evaluation is presented of several classes of drug for their efficacy in ameliorating the volitional ingestion of alcohol in the presence of an alternative fluid. Currently, two main experimental animal models of alcoholism are being used in this endeavor: (a) genetic lines or substrains of high alcohol preferring or high drinking rats; and (b) strains of nondrinking or low alcohol preferring rats which are induced chemically to prefer alcohol. Because of technical, methodological, and other issues surrounding the procedures used to assess the efficacy of a drug in reducing alcohol intake, several of the newer findings remain controversial. For example, serious side effects on the intake of food, caloric regulation, motor activity, or other functions would preclude the clinical utility of the drug. However, several drugs which affect monoaminergic neurons as well as opioid systems in the brain now seem to offer promise as agents which do possess clinical benefits. Two of these drugs, FG5606 (amperozide) and FG 5893 are essentially "antialcoholic" or anticraving and are without any significant side effects on cerebral mechanisms responsible for hunger, caloric intake, motor activity, or other physiological process. Amperozide, a 5-HT2 receptor antagonist with dopamine releasing properties, is particularly notable because of its irreversible nature in attenuating alcohol preference for months after its administration. It is concluded that future pharmacological research on presently available and newly developed compounds will provide exciting opportunities to the clinician who can utilize a particular drug as an adjunctive tool in the therapeutic treatment of the alcoholic individual. PMID- 7865141 TI - Adolescent substance abuse: the challenge for clinicians. AB - Substance abusing adolescents represent a unique population of patients within substance abusing communities. The interrelationship between the characteristics of problem substance use and the developmental tasks of adolescence is considerable and often presents the clinician with a diagnostic and treatment challenge. The identification, evaluation, treatment, and prevention of substance abuse among teens requires extensive knowledge of substance abuse as well as knowledge of the typical developmental tasks of adolescence. PMID- 7865142 TI - Addiction and family issues. AB - The insidious process of addiction in families creates a conspiracy of silence and denial coupled with unpredictable, unavoidable stress, trauma, and deprivation. It is a complex interplay of isolation, inhumane treatment, inconsistency, and indoctrination in these families that results in a process similar to brainwashing in which members gradually relinquish their own identity and develop robotlike patterns of adaptive behaviors. Interactive relationships are replaced with survival role performances, which allow the individual to participate in the family while avoiding and hiding the painful reality of what is happening. Adaptive survival behaviors continue to operate even after the individual leaves home and the survival maneuvers of an innocent child become the automatic behaviors of a dysfunctional adult. Understanding addictive family processes and the consequent adaptation of family members provides a basis for understanding the development of associated disorders and opens the way for effective treatment approaches. PMID- 7865143 TI - Dual diagnosis in the Walter B. Jones Alcohol and Drug Treatment Center. AB - The identification and management of substance abusers admitted with dual diagnosis problems or subsequently diagnosed during treatment with psychiatric syndromes, presents a therapeutic challenge to the hospital staff. This task becomes increasingly difficult because of the time constraints imposed by the length of the program (28 days) in our institution. An ongoing effort is in place to discover independent psychiatric illness in our population. If it exists, it is treated as effectively as possible within the constraints of time, with the expectation of enhancing aftercare treatment. The difficulties that arise in identifying psychiatric symptoms secondary to alcohol and drug use, from independent co-existing psychiatric illness will be described. PMID- 7865144 TI - Slouching toward a systems approach to treatment. AB - Both the health care sector generally and the alcohol and drug field are moving toward a truly systematic approach to treatment, accelerated by the anticipated advent of health care reform. There is considerable reluctance to develop systems. Many are not convinced of their necessity, and systematization inevitably involves a decrement in autonomy for the components of the system. Nor are systems panaceas; they have problems of their own, such as the bottleneck. But only true systems will be able to cope with the expected increase in demand for services that will accompany the universal entitlement of health care reform. Recent work giving the alcohol and drug treatment field an edge in systems development is discussed. Regrettably, the main motivation for deploying systems has become economic. They would more appropriately be justified by their potential for enhancing the efficacy of treatment. PMID- 7865145 TI - Developments in alcoholism treatment research: patient-treatment matching. AB - This article describes patient-treatment matching, a recent advance in alcoholism treatment research. A general description of the concept is presented and the challenges patient-treatment matching poses for investigators and for treatment providers are described. Project MATCH, a multisite clinical trial designed to test the matching hypothesis is used to illustrate approaches to addressing the research challenge. Two additional avenues of promising patient-treatment matching research, one relating to patient characteristics and the other to pharmacological treatments, are also summarized. The article concludes with a brief prescription for individual providers to implement and test treatment matching strategies in their own clinical practice. PMID- 7865146 TI - A comparison of mental health center operated detoxification programs in North Carolina. AB - The mental health center program in North Carolina provides detoxification services for substance abusers in community-based detoxification programs. Some of these programs are licensed as "social setting" and other as "medical nonhospital." Evaluation of one medical program and comparison with social setting programs revealed that the cost per bed in the social setting is 58% less, and that the cost for physicians and drugs constitute 17% of the medical detoxification program. However, because of the efficiency of the medical program, the costs per patient treated are comparable. Sixty-nine percent of the patients receive librium in the first 24 h after admission and 26% in the second 24 h in doses of 109 mg and 59 mg, respectively, and 62% required medication other than librium. As judged by the staff, 68% of the patients treated successfully completed the program. Follow-up of patients 30 days after discharge revealed that approximately 50% were in recovery. PMID- 7865147 TI - Issues on substance abuse in the North Carolina General Assembly. AB - In the North Carolina General Assembly during the 1993-1994 Session, 109 bills were introduced which dealt specifically with the issue of substance abuse. There were 42 bills introduced in the Senate and 67 bills introduced in the House. Three areas are discussed in this article: politics in general; substance abuse issues in the General Assembly; and one's role in affecting legislation. PMID- 7865148 TI - A model for answering the substance abuse educational needs of health professionals: the North Carolina Governor's Institute on Alcohol and Substance Abuse. AB - Physicians can play an increased role in recognizing, intervening, and moderating their patients' misuse of alcohol and other drugs. This article explores the need for educational changes to permit physicians to develop skills in prevention, screening, and office-based treatment. It includes a personal account by one of the authors of his experience in recognizing deficiencies in substance abuse education both in his own medical school training and in today's health science curricula in the United States. It reviews prior initiatives by NIAAA/NIDA to address curriculum needs and describes an innovative collaborative model in North Carolina called the Governor's Institute on Alcohol and Substance Abuse. The Institute was created in 1990 as a nonprofit corporation to promote education, research, and communication among health professionals. Some of the Institute's programs are described, including its curriculum integration project in the state's four medical schools. The article concludes that the time is right to introduce substance abuse concepts into basic and continuing education for all health professionals. PMID- 7865149 TI - Alcohol screening practices of primary care physicians in eastern North Carolina. AB - In our study, 616 primary care physicians of eastern North Carolina were surveyed for screening practices for detection of alcoholism in their patient population. We defined primary care as Family Medicine, Internal Medicine, Obstetrics and Gynecology, Pediatrics and Psychiatry. We defined eastern North Carolina as the 29 counties that Pitt County Memorial Hospital serves. In our survey we found that eastern North Carolina is medically underserved as well as having less resources for referral and consultation. In response to the questionnaire, we found that most physicians agreed on some numerical value for drinks per day, social drinks, and drinks per week while pregnant. Values for drinks per week and weekend binges generally reflected significant tolerance for heavy drinking behavior. We also found that physicians of the same specialty commonly agreed on answers but when compared to other specialties they differed. Physicians preferred personal and clinical screening methods to questionnaires such as CAGE. Most physicians did not prescribe Antabuse but did suggest to their patients to cut down on drinking. Physicians felt that their patients needed more education and support from the community as well as intervention at an early age. We conclude that physicians should receive more education concerning alcoholism and substance abuse. PMID- 7865150 TI - Interaction of acetaldehyde with plasma proteins of the renin-angiotensin system. AB - Chronic alcohol abuse may lead to hypertension by stimulating the activity of the renin angiotensin system (RAS). While there are reports on the alcohol associated increase of angiotensin II in rats and increases of plasma renin activity in rats and human alcoholics, the exact mechanisms of stimulation of the RAS activity is not clear. This study provides evidence for a biochemical interaction of acetaldehyde, the primary oxidative metabolite of ethanol, upon bilaterally nephrectomized (NEPEX) rat plasma that contains significant quantities of angiotensinogen and lacks active renin. Rat plasma served as the source of renin in this study. Preincubation of NEPEX plasma with 0.2 M acetaldehyde at 4 degrees C for 2 h resulted in a 21% increase in the angiotensin I (A I) formation by the rat plasma renin and 27% increase in the A I formation by the trypsinized rat plasma renin. When the rat plasma which contains modest quantities of endogenous angiotensinogen in addition to renin was preincubated with 0.2 M acetaldehyde at 4 degrees C for 2 h, the rate of A I formation was increased by 10%. Equivalent amounts of ethanol did not modify the rate of A I generation when added to NEPEX plasma or rat plasma. These results suggest the possibility of a biochemical interaction of acetaldehyde with the renin substrate which may enhance the activity of the RAS cascade, thereby contributing to hypertension in chronic alcoholics. PMID- 7865151 TI - S-adenosylmethionine generation and prevention of alcoholic fatty liver by betaine. AB - Earlier studies by other investigators have shown that S-adenosylmethionine (SAM) has the capacity to attenuate liver injury in experimental animals. In a recent study in this laboratory, it was shown that when supplemental dietary betaine was given to control and ethanol-fed rats at the level of 0.50% (W/V), SAM levels were doubled in the livers of control animals and increased fivefold in livers of ethanol-fed rats. The increased levels of SAM in the livers of ethanol-fed animals protected the livers from fatty infiltration due to ethanol feeding. In this study, an attempt was made to determine the minimum level of dietary betaine that protects against the fatty infiltration. Levels of betaine at 0.05%, 0.10%, 0.25%, and 0.50% in semiliquid control and alcohol diets were tested in rats for 30 days. When hepatic betaine, SAM, and triglyceride levels were determined, it was demonstrated that only the dietary level of betaine at 0.50% supplied enough hepatic betaine to generate the level of SAM that was required to protect against the alcoholic steatosis resulting from the dietary ethanol. These results suggest that betaine, when given in sufficient amounts, may be a promising therapeutic agent in the treatment of liver disease. PMID- 7865153 TI - Assessment of alcohol consumption and alcoholism in the elderly. AB - This study evaluates characteristics associated with alcohol consumption or alcohol-related problems in an elderly population, as detected by CAGE questionnaire and self-reported alcohol intake respectively. Data were obtained from a multidimensional study carried out in a community-dwelling population aged 70-75 (n = 1205, 389 males and 816 females) living in the city center of Brescia, in northern Italy. All information was gathered by self-report. Male gender, better mood, daily function, somatic health, not living alone, and being married were significantly associated with self-reported alcohol consumption. Male gender, poorer cognitive function, and income dissatisfaction were significantly associated with alcohol problems as detected by CAGE. Data suggest that self report of alcohol intake, though intrinsically loaded with imperfect internal consistency, does not necessarily indicate risk of alcoholism; on the contrary, it can reveal the positive psychological attitude of the drinking habit. CAGE questionnaire, which is sensitive to alcohol related problems, is associated with poor psychosocial conditions. PMID- 7865152 TI - Dietary salt and voluntary ethanol consumption in golden hamsters. AB - Adult male golden hamsters were maintained on powdered Purina chow and tap water, and were permitted continuous access to either a 15% or a 30% ethanol solution (v/v); after an initial 4-5 weeks of ethanol availability, hamsters had stabilized their intakes and were deriving an average of 1.25 and 1.96 g/day of absolute ethanol from the 15% and 30% solutions, respectively. When salt was added to the diet in increasing concentrations ranging from 4% to 10% over a period of 40 days, hamsters reduced chow-derived calories by up to 35%, increased tap water consumption by up to 50%, and increased consumption of ethanol solutions by up to 100%; when unadulterated Purina chow was reinstated, intakes of chow-derived calories, tap water, and ethanol solutions returned to baseline levels. Hamsters that were continuously maintained on unadulterated Purina chow, but with chow-derived calories matched to that of animals on the salt-adulterated diet, significantly increased their ethanol intake, but not their tap water intake; the increase in their ethanol intake was only about half as large as that of hamsters that had salt added to the diet, but the increase persisted even after ad lib feeding was reinstated. The results indicate that the addition of salt to the diet of hamsters produces large increases in ethanol consumption; furthermore, the increased ethanol intake is not simply the result either of a nonselective increase in fluid consumption or of the reduction in food intake that accompanies the addition of salt to the diet. Results are related to the possible role of the renin-angiotensin system in the control of ethanol consumption in the golden hamster. PMID- 7865154 TI - Reduced sensitivity to the effects of clonidine on ethanol-stimulated locomotor activity in adult mouse offspring prenatally exposed to ethanol. AB - Prenatal exposure to ethanol (EtOH) alters developing catecholamine (CA) systems and acute sensitivity to the locomotor stimulant effects of EtOH. As an extension of previous work involving CA agents, this study addressed whether prenatal EtOH exposure influences central norepinephrine (NE) systems by examining the motoric effects of the direct alpha 2 adrenoreceptor agonist clonidine given alone and in combination with a low-dose stimulant challenge of EtOH. Standard lab chow or liquid diets containing either 25% EtOH-derived calories (EDC), or 0% EDC (pair fed group) were given to pregnant C3H/He mice on gestation days 6-18. At 90 days of age, male offspring from each prenatal treatment group were monitored for 10 minutes in an open field following IP injections of clonidine (0, 0.0125, 0.025, or 0.05 mg/kg) and either EtOH (1.5 g/kg) or saline. In control offspring, clonidine suppressed locomotor activity and attenuated the stimulant response to EtOH in a dose-dependent fashion. In contrast, clonidine given alone did not suppress, but appeared to stimulate, activity in prenatal EtOH-exposed offspring. Furthermore, the ability of clonidine to attenuate the locomotor stimulant properties of EtOH was greatly reduced in prenatal EtOH-exposed animals. Taken together, these results indicate a shift to the right in the dose-response function for clonidine in prenatal EtOH-exposed offspring relative to control mice. Further, the results suggest that prenatal exposure to EtOH may result in long-lasting alterations in developing central NE systems, particularly presynaptic alpha 2 adrenoreceptor sensitivity. PMID- 7865155 TI - Effects of continuous versus limited access to ethanol on ethanol self administration. AB - Eight male, experimentally naive Long-Evans rats were housed in operant chambers 23 h per day following initiation to self-administer ethanol. While housed in the chambers, the animals had continuous access to food pellets according to a fixed ratio 1 schedule of reinforcement, 10% ethanol (v/v) according to a fixed ratio 4 schedule of reinforcement and water in a drinking tube with licks recorded via a drinkometer. Over a series of experimental phases, daily availability of the ethanol solution was limited to 16, 6, 4, 2, or 1 30-min period per day. The 1 30 min period access was examined during the 12th hour or the second hour of the daily sessions. Over the course of the experiment, total responses on the lever that operated the dipper, g/kg per day and number of ethanol drinking bouts per day decreased significantly as the number of daily access periods decreased. On the other hand, the number of dippers presented per ethanol bout, g/kg per ethanol bout and ethanol bout duration increased, with significant increases in dippers per bout occurring when one 30-min access period per day was provided. These data indicate that the size of a single ethanol drinking bout can be increased somewhat by limiting the opportunity to obtain ethanol reinforcement and agrees with earlier research that has shown similar effects. PMID- 7865156 TI - Acute effects of ethanol on recurrent inhibitory circuits of CA1 neurons in vivo. AB - This study examined the dose-dependent effects of acute ethanol on recurrent inhibitory mechanisms of hippocampal CA1 neurons in anesthetized rats. The effects of micropressure-ejected GABAergic compounds were studied on evoked field responses and recurrent inhibition of CA1 pyramidal neurons. None of the systemic doses of ethanol examined altered recurrent inhibition of CA1 neurons. In contrast, local application of both GABAa and GABAb compounds produced clear changes in evoked field responses and blocked recurrent inhibition. These results suggest that (a) recurrent inhibition in the CA1 region in vivo is resistant to the effects of ethanol, and (b) both GABAergic receptor subtypes modulate recurrent inhibition in the CA1 region in vivo. PMID- 7865157 TI - Chronic alcoholic myopathy and nutritional status. AB - To investigate the prevalence of alcoholic myopathy and its relationship to the nutritional status, we performed a muscle biopsy on the vastum lateralis of 60 consecutive hospitalized alcoholic patients using a Tru-Cut needle, processing it for light microscope and ultrastructural analysis. The nutritional status was assessed by anthropometric measurements such as midarm circumference, triceps skinfold and midarm muscle area, and serum albumin. The hallmark of chronic alcoholic myopathy, fiber muscle atrophy, was present in 33% of the patients, necrosis scarcely being observed (1.5%). Ultrastructural alterations as lipid and glycogen accumulation or mitochondrial and myofibrillar alterations were nonspecific and observed in nearly all the cases where atrophy was present. Malnutrition was frequent in our patients: 39% and 34% showed a triceps skinfold and a midarm muscle area, respectively, under the fifth populational percentile. Patients with muscle fiber atrophy or ultrastructural changes showed a worse nutritional status, not only regarding muscle protein (assessed by midarm muscle area or creatininuria and explained by fiber atrophy), but also regarding fat stores assessed by triceps skinfold. Toxic effect of ethanol and malnutrition may act synergistically leading to chronic alcoholic myopathy. PMID- 7865158 TI - Ethanol self-infusion into the ventral tegmental area by alcohol-preferring rats. AB - The ventral tegmental area (VTA) and its projections have been implicated in the reinforcing effects of drugs of abuse. Selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) lines of rats were used to evaluate the reinforcing actions of ethanol in the VTA using intracranial self-administration (ICSA) operant procedures. P rats self-administered nanoliter quantities of 50 200 mg% ethanol in artificial CSF directly into the VTA whereas NP rats had low levels of responding at these ethanol concentrations. Responses on the active lever were 50-fold higher for the P compared with the NP rats for the self infusion of 150 mg% ethanol. NP rats responded at the same level on the active and inactive levers at all ethanol concentrations and had low responses/session (3 to 15 total responses) at all concentrations. Further, operant responding on the active lever was reduced when artificial CSF alone was substituted for 100 mg% ethanol, and responding on the active lever was reinstated when ethanol was returned. For one group of rats, an illuminated house light served as a discriminative stimulus, which signalled the availability of ICSA, while a cue light was paired with the onset of ethanol infusion. Extinction in the presence of these stimuli required 6-7 sessions. However, only 2-3 extinction sessions were necessary for another group trained without stimulus cues, suggesting that cues paired with the ICSA of ethanol can acquire conditioned reinforcing properties. The findings indicate that ethanol can act as a reinforcer when administered directly into the VTA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865160 TI - Acute ethanol decreases NMR relaxation times of water hydrogen protons in fish brain. AB - The traditional belief about ethanol's mechanism of action is based on ethanol's lipophilicity and capability to penetrate and disorder lipid bilayers. This traditional belief is now being supplanted by growing evidence that ethanol has relatively selective actions on certain synaptic receptors, such as those for NMDA, serotonin, and GABA. It was recently argued that these receptor specificities are secondary to a preferential ability of ethanol to displace membrane bound water in the domains of certain receptors. The data obtained in this study are consistent with the original hypothesis: any disorganization of cellular water by ethanol will be detectable by proton nuclear magnetic resonance (NMR) spectroscopy. In particular, the relaxation times of water hydrogen protons reflect how constrained water molecules are by the macromolecules within cells. The relaxation time of "bulk" water is lengthened relative to water molecules that are under the influence of electromagnetic fields of macromolecular surfaces within cells. Here, we tested this hypothesis in living fish, which dosed themselves by swimming in water that had added ethanol. Estimates of brain alcohol at 5 min after initial exposure revealed that the brain concentration was only about 1/3 that of the water in which they were swimming. The average value of the NMR relaxation time T1, but not T2, was decreased at 5 min (when brain concentrations were on the order 100 mM) and reached statistical significance at 10 and 30 min after initial exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865159 TI - Ethanol attenuation of ganglioside sialylation and neuritogenesis. AB - Neurite-producing cultured embryonic chick brain neurons in 96-h culture were exposed chronically to 25 mM ethanol for a 72-h period. Neurital plasma membrane extension was markedly attenuated in the ethanol-exposed neurons as compared with ethanol-free control cultures. The rate of biosynthetic sialylation of gangliosides, which are major structural sialoglycosphingolipid components in the exofacial lipid bilayer of the neurital plasma membrane, decreased to about half that in the alcohol-free neurons. The findings show that ganglioside sialylation in the morphodifferentiating central nervous system neuron is significantly attenuated by chronic exposure to a moderate dose of ethanol. Depression of ganglioside-dependent neuritogenesis may represent a mechanism for development of the central nervous system component of the fetal alcohol syndrome. PMID- 7865161 TI - Quantifying ethanol by high performance liquid chromatography with precolumn enzymatic conversion and derivatization with fluorimetric detection. AB - We quantified ethanol by measurement of the subsequent increase in acetaldehyde after reaction with alcohol dehydrogenase and nicotinamide adenine dinucleotide (ADH-NAD) with a fluorimetric HPLC method. Ethanol standards ranging from 0.3 to 200 mg/dl were investigated and the limit of quantitation of the fluorimetric HPLC method was found to be 6 mg/dl. The accuracy of the HPLC method was assessed by assaying blood samples containing 6-200 mg/dl of ethanol and comparing its results to those of the ADH-NAD enzymatic method (r2 = 0.993). The coefficients of variation for intraassay (assayed ten times) and interassay (assayed on 7 consecutive days) were 6.7% and 9.3% for blood samples containing 50 mg/dl of ethanol and 4.0% and 17.9% for blood samples containing 200 mg/dl of ethanol. The blood ethanol concentrations of a volunteer after a pulse of 0.3 g/kg of ethanol determined with the described HPLC method were correlated to the results from the ADH-NAD enzymatic method (r2 = 0.986). In conclusion, the fluorimetric HPLC method for measurement of ethanol here described is of potential clinical utility. PMID- 7865162 TI - Visual P300: an interlaboratory consistency study. AB - The P300 component of the event-related potential is reduced in both abstinent alcoholics and in males at high risk for developing alcoholism. Here, 96 males (mean = 22.1 years) who were part of an interlaboratory (n = 6) consistency study in the national COGA (Collaborative Study on the Genetics of Alcoholism) Project were subjects in a visual target selection paradigm. Each of the participating laboratories used the same experimental design, hardware and software. Each subject received a randomized series of target, nontarget and novel visual stimuli, and upon detecting the target stimulus, was required to make a button press as quickly as possible. Statistical analyses indicated that there were no significant differences in P300 amplitude and latency at the Pz electrode under any of the aforementioned conditions across laboratories. Thus, the interlaboratory consistency of the visual P300 indicates that it may be of utility in a national collaborative study on the genetics of alcoholism. PMID- 7865164 TI - 2nd International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland, 18-22 November 1994. Abstracts. PMID- 7865163 TI - Recovery of muscular energy status in chronic alcoholics after 2 weeks of abstinence. AB - Repeated and excessive consumption of alcohol leads to pathophysiological disorders in skeletal muscles. A successful management of this syndrome requires a strict abstinence and a nutritionally adequate diet. We propose here a simple and noninvasive investigation using 31P magnetic resonance spectroscopy (MRS) to monitor the recovery of the basal energy status of eminence thenar muscles from documented chronic alcoholic patients during a controlled 15-day period of abstinence. Cessation of alcohol abuse induced a significant recovery of the PCr/(PCr+P(i)) ratio otherwise depressed before the abstinence. On the contrary, the relative level of free inorganic phosphate decreased, whereas intracellular pH was not affected. These results demonstrate (a) the rapid improvement of basal muscular energy metabolism during abstinence for patients with a chronic and heavy alcohol consumption, and (b) the feasibility of a follow-up of this recovery by serial examinations using 31P MRS. PMID- 7865165 TI - d-cycloserine adjuvant therapy to conventional neuroleptic treatment in schizophrenia: an open-label study. AB - D-cycloserine, a partial agonist at the strychnine-insensitive glycine site of the NMDA receptor complex, was tested as adjuvant treatment to conventional neuroleptics in chronic schizophrenic volunteers. The drug was administered, o.a.d., at the daily dose of 250 mg for six weeks. Mental status outcome measures were completed at the end of each week of treatment. The major finding was a deterioration of the patients' clinical condition, specifically of their psychotic symptoms. These preliminary results are discussed among others in view of d-cycloserine pharmacologic properties and recent findings on the interaction between NMDA agonists and dopamine system. This study, finally, suggests the need for a controlled dose-finding trial to establish the activity and a therapeutic "window" of this drug in schizophrenia. PMID- 7865166 TI - On the roles of dopamine D-1 vs. D-2 receptors for the hyperactivity response elicited by MK-801. AB - The present study was aimed at clarifying to what extent the hypermotility induced by the uncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 depends on dopamine (DA) D-1 compared to D-2 receptor tone. The D-1 receptor antagonist SCH 23390 was found to reduce locomotion to a greater extent in MK-801 treated than in vehicle-treated mice, whereas the reverse appeared to be the case for the DA D-2 receptor antagonist raclopride. In other words, MK-801-induced hyperactivity was more readily antagonized by SCH 23390 than by raclopride and, thus, DA D-1 receptors seem to be more important than D-2 receptors for MK-801 induced hyperactivity. These results are in line with our previous observation that MK-801 generally interacts synergistically with a DA D-1 but not with a D-2 receptor agonist in monoamine-depleted mice. In view of the possible role of deficient glutamatergic neurotransmission in schizophrenia, our findings underline the importance of investigating the efficacy of selective DA D-1 antagonists in this disorder. PMID- 7865167 TI - Glycine site antagonists abolish dopamine D2 but not D1 receptor mediated catalepsy in rats. AB - Catalepsy--a state of postural immobility (akinesia) with muscular rigidity (rigor)--and reduced locomotion in animals are behavioral deficits showing similarities with symptoms of Parkinson's disease (PD). The effects of the glycine site antagonists 7-chlorokynurenate and (R)-HA-966 on haloperidol-(D 2 antagonist) and SCH 23390- (D 1 antagonist) induced catalepsy and reduced locomotion are investigated in rats. Both antagonists dose-dependently counteract dopamine D 2 receptor mediated catalepsy but they have no influence on locomotion. Neither 7-chlorokynurenate nor (R)-HA-966 has any effect on dopamine D 1 receptor mediated catalepsy. This finding is surprising, since NMDA receptor antagonists counteract both, dopamine D 1 and D 2 receptor mediated catalepsy. D 1 and D 2 receptors are located on different populations of neurons. Thus, the present findings suggest that these different neuronal populations have different sensitivity for ligands binding at the glycine binding site of the NMDA receptor. PMID- 7865168 TI - Effect of dizocilpine (MK-801) on the catalepsy induced by delta 9 tetrahydrocannabinol in mice. AB - Mice treated with delta 9-tetrahydrocannabinol (THC; 5 and 10 mg/kg i.v.) showed the catalepsy in high bar test, and median descent latencies of catalepsy were about 150 sec. Dizocilpine (MK-801, 0.05 and 0.1 mg/kg), non-competitive N-methyl D-aspartate (NMDA) antagonist, significantly attenuated THC-induced catalepsy. Furthermore, the anticataleptic effect of MK-801 on THC-induced catalepsy was blocked by acetylcholine agonist oxotremorine (0.005 mg/kg) and dopamine antagonist haloperidol (0.01 mg/kg), but not by NMDA. Oxotremorine, haloperidol, and NMDA themselves did not affect THC-induced catalepsy at the doses used. These results suggest that the anticataleptic effect of MK-801 on THC-induced catalepsy may be developed through dopaminergic and acetylcholinergic neuronal systems. PMID- 7865169 TI - Organization of the human serotonin transporter gene. AB - The gene encoding the human serotonin transporter (5-HTT) has been isolated and characterized. The human 5-HTT gene is composed of 14 exons spanning approximately 31 kb. The sequence of all exons including adjacent intronic sequences and a tandem repeat DNA polymorphism (VNTR) has been determined and deposited in the EMBL/GenBank data base with the accession numbers X76753 to X76762. The characterization of 5-HTT gene will aid to advance molecular pharmacologic studies of 5-HT uptake regulation and facilitate investigations of its role in psychiatric disorders. PMID- 7865170 TI - Facilins, a novel class of biological factors that facilitate the aortic response to dopamine and other biogenic amines. AB - Biological fluids and tissues extracts were shown to contain biological factors, termed facilins, that facilitate the dopamine-, adrenaline-, and serotonin mediated aortic contraction at concentrations devoid of any direct effect. Cyproheptadine and phentolamine antagonized the direct contracting effect of biogenic amines, but not the facilitated component of the aortic response thus indicating that the mechanism of action of facilins was unlike that of biogenic amines. Fresh schizophrenics' CSF displayed a stronger facilitating effect than normal CSF on the dopamine-mediated aortic response. This finding, however, was not confirmed with samples kept frozen for prolonged periods of time. Multiple molecular forms of facilins were detected in rabbit serum. Those with a high apparent molecular weight were proteinous and were neither insulin nor other factors known for their contracting effects on the aorta such as epidermal growth factor, transforming growth factor-beta, and platelet-derived growth factor. PMID- 7865171 TI - Reduced concentrations of the alpha-subunit of GTP-binding protein Go in schizophrenic brain. AB - Concentrations of the alpha-subunits of GTP-binding protein, Go (Go alpha) and of Gi2 (Gi2 alpha) in 6 areas (the hippocampus, parahippocampus, putamen, caudate head, orbital frontal cortex, and lateral temporal cortex) of control and schizophrenic postmortem brains were investigated using the highly sensitive enzyme immunoassay method. There was a significant decrease in Go alpha in the hippocampus and caudate head of the right hemisphere in schizophrenic patients compared to controls; the ANOVA (a general linear model; SAS Type II) demonstrated a significant diagnosis x side interaction only in the hippocampus. In other areas of the brain, analysis by grouping under diagnosis, side, age, gender, and postmortem delay showed no significant deviations in Go alpha between controls and schizophrenics. The concentrations of Gi2 alpha did not differ significantly in any area. These findings contrasted with the results yielded by ADP-ribosylation, which showed decreased pertussis toxin ADP-ribosylated amounts in the hippocampus and putamen of the contralateral (left) hemisphere. Some abnormal receptor-Go or Gi 1 signalling in hippocampus, putamen or caudate head may be involved in the pathogenesis of schizophrenia. PMID- 7865172 TI - Effect of pertussis toxin on the response of rat medial prefrontal cortex cells to the iontophoresis of serotonin receptor agonists. AB - In this study, we examined the response of spontaneously active as well as quiescent cells (L-glutamate-activated) in the rat medial prefrontal cortex (mPFc) to the iontophoresis of 2-methylserotonin (2-Me-5-HT, 5-HT3 receptor agonist), (+/-)-2,5-dimethoxy-(4-iodo-phenyl)-2-aminopropane (DOI, 5-HT2A,2C receptor agonist), 8-hydroxy-N,N-di-propylamino tetralin (8-OH-DPAT, 5-HT1A receptor agonist) and gamma-aminobutyric acid (GABA, a non-selective GABA receptor agonist) after the intracerebral administration of pertussis toxin, an inactivator of the Gi/o protein. This was accomplished using the techniques of extracellular single cell recording and iontophoresis. The administration of pertussis toxin (0.5 microgram, 24 hours before the experiment) into the mPFc did not alter the response of mPFc cells to the iontophoresis of DOI, 2-Me-5HT or GABA compared to saline treated controls. However, the response of mPFc cells to the iontophoresis of 8-OH-DPAT was significantly attenuated in the animals pretreated with pertussis toxin compared to controls. These results suggest that the 5-HT1A but not 5-HT2A,2C or 5-HT3 receptor is coupled to the Gi/o protein. PMID- 7865173 TI - The antigonadotrophic effect of melatonin in Syrian hamsters is modulated by prostaglandin. AB - PGE2 was shown to play an essential role in the gonado-inhibiting effect of melatonin in Syrian hamsters by transforming the neuroendocrine signal to gonadal reactivity. Prostaglandin is a vital link in the transduction of photoperiodic information into gonadal function and the difference in its levels brought about by melatonin given at different times of the day could explain the phenomenon why gonadal involution occurs only upon administration of melatonin towards the end of the day. It appears also that the melatonin signal is decoded in the pituitary, probably involving the short loop negative feedback of LH on LH-RH hormones. PMID- 7865174 TI - Effects of nefiracetam on deficits in active avoidance response and hippocampal cholinergic and monoaminergic dysfunctions induced by AF64A in mice. AB - The effects of nefiracetam [DM-9384; N-(2,6-dimethyl-phenyl)-2-(2-oxo pyrrolidinyl)acetamide] and of phosphatidylcholine on a step-up active avoidance response, locomotor activities and regional brain cholinergic and monoaminergic neurotransmitters in AF64A-treated mice were investigated. Intracerebroventricular (i.c.v.) injection of AF64A (ethylcholine mustard aziridinium ion; 8 nmol/ventricle) impaired acquisition and retention of the avoidance task, and increased vertical and horizontal locomotor activities. Regional levels of acetylcholine, noradrenaline, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly decreased and homovanillic acid (HVA) levels were increased in the hippocampus but not in the septum, cerebral cortex or striatum of AF64A-treated animals. Administration of nefiracetam (3 mg/kg, p.o.) twice daily for 9 days to AF64A-treated animals ameliorated the deficit in active avoidance response in addition to attenuating the increase in locomotor activities. In parallel with these behavioural effects, nefiracetam reversed AF64A-induced alterations in the hippocampal profiles of cholinergic and monoaminergic neurotransmitters and their metabolites. In contrast, administration of phosphatidylcholine (30 mg/kg, p.o.) twice daily for 9 days had no significant effect on the deficit in active avoidance response, despite significantly reversing the decrease in acetylcholine levels in the hippocampus. These results indicate that the effects of nefiracetam on AF64A-induced behavioural deficits are probably due to its ability to facilitate both cholinergic and monoaminergic neurotransmitter systems. PMID- 7865175 TI - Dopaminergic function in rat brain after oral administration of calcium-channel blockers or haloperidol. A microdialysis study. AB - Microdialysis technique was used to study the effects of both acute and repeated oral administration of calcium-channel blockers (flunarizine, cinnarizine, verapamil, nifedipine and nicardipine) in dopaminergic function in rat brain and to compare them to the effects of haloperidol. Acute flunarizine, nicardipine or haloperidol increased extracellular levels of dopamine (DA) or metabolites. After repeated (18 days) administration, nicardipine, nifedipine, verapamil or haloperidol increased and flunarizine decreased extracellular striatal levels of dopamine or metabolites. Chronic treatment with calcium-channel blockers or haloperidol failed to block K(+)-evoked release of dopamine. This suggests that the calcium-channel blockers used in this study do not influence calcium entry necessary for DA release. An acute challenge with haloperidol caused either no change or a decrease in extracellular levels of DA or metabolites after repeated administration of calcium-channel blockers or haloperidol. This is considered to be due to the lesser response of dopaminergic neurons because of treatment. A neuroleptic-like mechanism of action together with a decrease in firing activity and/or a reduced dopamine re-uptake of dopaminergic neurons are considered. PMID- 7865176 TI - The effect of reserpine treatment in vivo upon L-dopa and amphetamine evoked dopamine and DOPAC efflux in vitro from the corpus striatum of male rats. AB - In the present experiment we tested the effects of L-DOPA and amphetamine upon dopamine and DOPAC efflux in vitro from superfused corpus striatal tissue fragments of male rats who had been pretreated with reserpine. Male rats were treated with reserpine (5 mg/kg) or its vehicle at 24 hours prior to sacrifice and superfusion of the corpus striatum. Two different modes of L-DOPA (5 microM) and amphetamine (10 microM) stimulation, a brief 10-minute and a continuous 60 minute infusion, were tested for their ability to evoke striatal dopamine and DOPAC efflux. Depletion of monoamine storage capacity as achieved with reserpine significantly reduced the amount of basal dopamine and DOPAC released from superfused striatal tissue fragments of male rats. Although basal release rates were significantly reduced, the amount of dopamine and DOPAC released in response to in vitro L-DOPA infusions (10 or 60 minute infusions) was equivalent between reserpine and vehicle treated animals. In contrast, amphetamine stimulated DA release was significantly reduced in male rats treated with reserpine. For both L DOPA and amphetamine, significantly greater amounts of dopamine were obtained with the 60- versus 10-minute infusion modes. These results demonstrate that the capacity for L-DOPA, but not amphetamine, to evoke dopamine efflux is unaltered under conditions when monoamine storage ability is diminished. PMID- 7865178 TI - I. c. v. dopamine fails to alter adrenomedullary function in rats. AB - Intracerebroventricularly (i.c.v.) administered dopamine (50-400 micrograms/kg, 30 min; 400 micrograms/kg, 2 and 4 h) did not induce statistically significant changes in heart adrenaline (presumed to represent the adrenaline release from the adrenals). Only the highest dose (400 micrograms/kg, 30 min) brought about significant increase in adrenal dopamine (reflecting the catecholamine synthesis), accompanied by increase in heart dopamine, indicating leakage of dopamine into the peripheral circulation. The results did not support involvement of the central dopamine receptors in the short-term control of the adrenomedullary function in rats. PMID- 7865177 TI - Effects of D-cycloserine and (+)-HA-966 on the locomotor stimulation induced by NMDA antagonists and clonidine in monoamine-depleted mice. AB - We have previously observed that an N-methyl-D-aspartate (NMDA) antagonist in combination with the alpha 2-adrenoceptor agonist clonidine produces a marked locomotor stimulation in monoamine-depleted mice. In this paper we report on how the partial glycine agonists D-cycloserine (high intrinsic activity) and (+)-HA 966 [(+)-3-amino-1-hydroxypyrrolid-2-one; low intrinsic activity] affect this response; the interaction with both an uncompetitive and a competitive NMDA antagonist was investigated. (+)-HA-966 was found to counteract the locomotor stimulation produced by clonidine combined with either an uncompetitive (MK-801 = dizocilpine) or a competitive [D-CPPene = 3-(2-carboxypiperazine-4-yl)-1-propenyl 1-phosphonic acid] NMDA antagonist. D-cycloserine potentiated the locomotor stimulation produced by either NMDA antagonist combined with clonidine, although statistical significance was achieved only in the case of MK-801. If the present hyperactivity model has any relevance for psychosis the prediction based on the present results would be that d-cycloserine, contrary to current hopes, might not be so effective in schizophrenia, whereas (+)-HA-966 might be an interesting candidate. PMID- 7865179 TI - Monoamine oxidase inhibition by the MAO-A inhibitors brofaromine and clorgyline in healthy volunteers. AB - The present study compared the extent and duration of MAO inhibition by the selective and reversible MAO-A inhibitor brofaromine with the selective and irreversible MAO-A inhibitor clorgyline using amine pressor tests and excretion of urinary amine metabolites (MHPG, tryptamine). The pharmacological characterization of clorgyline as an irreversible and brofaromine as a reversible MAO-A inhibitor in clinically effective doses was confirmed in humans. PMID- 7865180 TI - The composite 'peritoneal membrane'. PMID- 7865181 TI - Pathophysiological description of the ultrastructural changes of the peritoneal membrane during long-term continuous ambulatory peritoneal dialysis. AB - Some of the patients on continuous ambulatory peritoneal dialysis (CAPD) develop with time on treatment an increased transperitoneal transport of small solutes, implying that glucose is more rapidly absorbed from the dialysate. Hence, the dialysate/serum crystalloid osmotic gradient dissipates at a faster rate, so that ultrafiltration failure may result. The pathophysiological correlates to these changes are not well understood. However, it seems that with time on CAPD, there are changes in the submesothelial interstitium, affecting both the ground substance and spacing and orientation of collagen fibers. There may also be mesothelial alterations with patchy shedding of the cells. The present article discusses these changes in terms of a modified three-pore model of peritoneal permeability. In this model, the capillary walls act as a major barrier for solutes ranging in size from inulin (molecular radius 14 A) to macromolecules (molecular radius > 30 A). However, for solutes smaller than inulin both capillary wall and insterstitium contribute to the blood-peritoneum transport impedance. The increased small-solute exchange sometimes occurring in long-term CAPD can be explained either by recruitment of vascular surface area, due, e.g., to an increased capillarization of the peritoneal membrane with time, or, more likely, a drop in the interstitial transport resistance to small solutes. The latter possibility is supported by the often more pronounced increase in the transperitoneal transfer of small solutes than that of macromolecules over time in CAPD. PMID- 7865182 TI - Ultrafiltration and clearance studies in human isolated peritoneal vascular loops. AB - Eight samples of human peritoneal tissue were obtained from patients undergoing hemicholectomy for cancer. An artery and a vein were cannulated and perfused with blood in vitro with a special circuit able to provide different perfusion pressures. Ultrafiltration and clearance studies were performed in these samples. Both ultrafiltration and small-solute clearances linearly correlated with the blood flow, demonstrating a strong dependence on this parameter. The peritoneal capillary showed a typical filtration pressure equilibrium with a constant filtration fraction at different blood flows. The results suggest that the blood flow may be a factor limiting the efficiency of peritoneal dialysis both in terms of mass transfer coefficients and maximal ultrafiltration rates. PMID- 7865183 TI - Pathophysiology of hypertension in patients on renal replacement therapy. AB - Hypertension is a frequent problem in patients with renal failure, whether or not they are on renal replacement therapy. Little is known, however, about the pathophysiological mechanisms leading to an elevation of blood pressure. Although there is a relationship between body fluid volumes and blood pressure, it is unlikely that hypertension can be explained on the basis of volume expansion alone. Haemodynamically, hypertension in renal failure is characterized by an increased peripheral vascular resistance, but there is no convincing evidence that this is secondary to a high-output state. Among the pressor systems that have been implicated, the renin-angiotensin system and the adrenergic system are likely candidates, but overactivity of these systems or enhanced reactivity to the mediators still cannot explain all elements of renal failure associated hypertension. Therefore, other factors, such as intracellular electrolytes and the Na-K pump, are under scrutiny. However, given the heterogeneity of patient groups studied so far, it is virtually impossible to draw any meaningful conclusions about the pathogenesis of high blood pressure in patients on renal replacement therapy. PMID- 7865184 TI - Control of blood pressure in long slow hemodialysis. AB - Hypertension is a major cause of mortality and morbidity in hemodialysis patients. A long slow dialysis (8 h/session) was used in 692 unselected patients. It allowed for an excellent control of blood pressure without the need of antihypertensive medications. Cardiovascular morbidity and mortality were lower in the subgroups of patients presenting with a lower predialysis mean arterial pressure. The control of the extracellular volume with a low rate of intradialytic hypotensive episodes is the most probable explanation of this result. Another possible mechanism is the restoration by the large dose of dialysis of the nitric oxide vasodilator action inhibited by the accumulation of dimethylarginine in the serum of uremic patients. PMID- 7865185 TI - Influence of interdialytic weight gain on blood pressure in hemodialysis patients. AB - The role of fluid overload in the pathogenesis of hypertension in hemodialysis patients is not clear. One problem is the lack of techniques to determine the fluid state. Recent new noninvasive techniques have become available which make it possible to accurately determine the dry weight in these patients. Therefore, we studied the influence of interdialytic weight gain on interdialytic blood pressure in 10 normotensive and 10 hypertensive hemodialysis patients without antihypertensive medication. The dry weight was determined with echography of the vena cava. The blood pressure was measured during 2-day and 3-day interdialytic periods using Spacelabs 90207 ambulatory blood pressure monitors. Mean systolic and diastolic blood pressures of the last day of the interdialytic period were compared with mean systolic and diastolic blood pressures of the 1st day of the interdialytic period. Although the interdialytic weight gain in the normotensive and hypertensive patients was greater during the 3-day than during the 2-day interdialytic period, the interdialytic systolic and diastolic blood pressure changes were not greater during the 3-day period. Also, the interdialytic blood pressure rise did not correlate significantly with weight gain, neither in the normotensive nor in hypertensive patients. No significant interdialytic blood pressure changes were found between the normotensive and the hypertensive patients. We conclude that fluid overload does not seem to play a major role in interdialytic blood pressure control in normotensive and hypertensive hemodialysis patients. PMID- 7865186 TI - Clinical aspects of cardiomyopathy in dialysis patients. AB - The burden of cardiac disease in dialysis patients is high. Congestive heart failure, ischemic heart disease, left ventricular hypertrophy, and systolic dysfunction occur frequently and are associated with an adverse prognosis. In addition, during dialysis therapy anemia, hypoalbuminemia, low blood pressure, and lower serum creatinine levels are adverse predictors of mortality. Risk factors for systolic dysfunction include older age, ischemic heart disease, hyperparathyroidism, and smoking. Risk factors for left ventricular hypertrophy include older age, hypertension, anemia, and diabetes mellitus. Interventions with potential for improving cardiomyopathy include normalization of hematocrit with erythropoietin, improved uremia therapy, and angiotensin-converting enzyme inhibitors. Trials to determine the most appropriate interventions to reduce the impact of cardiac disease in chronic uremia are urgently required. PMID- 7865187 TI - Pathophysiology of left ventricular hypertrophy in dialysis patients. AB - Left ventricular hypertrophy is a frequent cardiovascular alteration in end-stage renal disease patients on hemodialysis which is associated with increased morbidity and mortality. Hypertrophy results from chronic flow and pressure overload and from poorly understood neurohumoral alterations. Clinical symptomatology associated with ventricular hypertrophy is related to diastolic dysfunction which characterizes this condition. The symptoms are (1) an unusual sensitivity to volume changes such that hypotension and hemodynamic instability and/or pulmonary edema occur with small volume variations and (2) a high frequency of supraventricular arrhythmias. PMID- 7865188 TI - Fouling of ultrafiltration and hemodialysis membranes by plasma proteins. PMID- 7865189 TI - Citrate anticoagulation and divalent cations in hemodialysis. AB - Anticoagulation with citrate in combination with a calcium-free, magnesium containing dialysate (Ca-Mg+) and intravenous supplementation of calcium is a safe procedure in renal failure patients at high risk of bleeding. Since magnesium may antagonize the anticoagulant effect of citrate by forming complexes with citrate, we studied the in vitro and in vivo interactions of calcium and magnesium on citrate anticoagulation. In the in vitro studies the activated partial thromboplastin time (APTT) was 88 s, both after addition of 3.0 mumol magnesium and after addition of 1.0 mumol calcium. The combination of 2.4 mumol magnesium and 1.0 mumol calcium achieved similar APTT values of about 35 s as 3.5 mumol calcium alone. Moreover, in a Lee-White blood clotting time, the anticoagulant effect of 7 mumol citrate was neutralized by either 10.5 mumol of a mixture of the two cations or 10.5 mumol calcium chloride alone. In 6 chronic hemodialysis patients the in vivo interactions of calcium and magnesium on citrate were measured. At the dialyzer outlet, the whole blood activated clotting time (ACT) was significantly (p < 0.05) shorter during dialysis with a Ca-Mg+ dialysate than during dialysis with a calcium- and magnesium-free dialysate (Ca Mg-). With the Ca-Mg- dialysate the ACT at the dialyzer outlet was still significantly longer than the ACT in the arterial line before citrate infusion. We also compared the serum concentrations of calcium and magnesium during the Ca Mg- dialysate which was used in combination with intravenous calcium and magnesium supplementation - 0.18 and 0.08 mmol/min respectively--and during a conventional calcium- and magnesium-containing dialysate (Ca+Mg+).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865190 TI - Two-compartment model of cholesterol kinetics for establishment of treatment strategy of LDL apheresis in nephrotic hypercholesterolemia. AB - Cholesterol kinetics in the time course after LDL apheresis using a dextran sulfate cellulose column was analyzed by adapting a two-compartment cholesterol kinetic model. Fifteen sets of serial serum cholesterol concentrations after LDL apheresis from 4 patients with drug-resistant nephrotic hypercholesterolemia due to focal glomerulosclerosis (FGS) were analyzed and cholesterol kinetic parameters were estimated with the nonlinear least-squares method. The fractional cholesterol catabolic rates (Kc; 0.171 +/- 0.073/day, mean +/- SD) were markedly decreased as reported in familial hypercholesterolemia (homo: 0.101/day, hetero: 0.280/day). Cholesterol generation rates (G; 68.0 +/- 28.7 mg/dl/day, mean +/- SD) considerably overlapped the normal range (39.2-77.5 mg/dl/day). This result was compatible with an earlier report that Kc was reduced earlier than G in nephrotic hypercholesterolemia. The time average serum cholesterol concentrations (TAC) in the rebound phase after LDL apheresis can be simulated using these kinetic parameters by the Runge-Kutta-Gill method. According to our previous report, TAC must be reduced to under a near-normal level in order to obtain a beneficial effect on nephrotic syndrome due to FGS. In 10 sets out of the 15, once-weekly treatment of LDL apheresis was sufficient to achieve this aim, but in the remaining 5 cases, more frequent LDL apheresis up to twice a week was necessary in the early phase of treatment. In conclusion, the two-compartment cholesterol kinetic model is useful in clarifying the abnormal cholesterol kinetics in nephrotic syndrome and may be helpful in establishing a more rational strategy of LDL apheresis for nephrotic hypercholesterolemia. PMID- 7865191 TI - Peritoneal solvent drag reflection coefficients are within the physiological range. AB - Previous estimates of the peritoneal solvent drag reflection coefficient (sigma) are widely disparate; some are outside the range expected for a semipermeable membrane (i.e., between 0 and 1). We have evaluated a novel method for determining sigma in a rabbit model of peritoneal dialysis. Test solute was infused intravenously, and sequential 2-hour isotonic and hypertonic exchanges (40 ml/kg) were performed in random order. Test solute was also added to the instilled hypertonic dialysis solution to inhibit transperitoneal solute diffusion during this exchange. Eight experiments were performed with creatinine as test solute and glucose as osmotic solute, and six experiments were performed with glucose as test solute and mannitol as osmotic solute. When using isotonic dialysis solution, the dialysate/plasma concentration ratio (D/P) for both test solutes increased throughout the exchange (p < 0.001). When using hypertonic dialysis solution, D/P creatinine was initially near 1 and decreased during the 1st hour of the exchange (p < 0.05); D/P glucose (as test solute) was initially 0.82 +/- (SEM) 0.07 and did not change during the exchange. The peritoneal diffusive permeability-area product (PA) was determined by fitting a mathematical model to the time dependence of the dialysate test solute concentration during the isotonic exchange using PA as an adjustable parameter, and sigma was determined in like manner during the hypertonic exchange using sigma as an adjustable parameter (and assuming a PA value equal to that during the isotonic exchange). The creatinine PA (1.37 +/- 0.28 ml/min) was higher than that for glucose (0.62 +/- 0.07 ml/min) as expected based on their solution diffusion coefficients. Creatinine and glucose sigma values were 0.38 +/- 0.06 and 0.43 +/- 0.05, respectively. We conclude that peritoneal sigma values for creatinine and glucose are within the physiological range. PMID- 7865192 TI - The TAPS Project. 22: A five-year follow-up of long-stay psychiatric patients discharged to the community. AB - A group of 114 long-stay patients in Friern and Claybury Hospitals was assessed while in hospital, and then again one year and five years after discharge to community placements. Neurotic symptoms, verbal and non-verbal behaviour and, most notably, negative symptoms all improved between the two community follow-up interviews. Patients were living under much less restrictive conditions in the community, and their appreciation of this freedom continued to grow over the years. Their social networks were enriched by an increase in the number of friends in the first year after discharge and in the number of confidants in the subsequent four years. There were no adverse outcomes, but these conclusions cannot yet be said to apply to all long-stay residents of mental hospitals. PMID- 7865193 TI - Economics and schizophrenia: the real cost. AB - The total direct cost of treating schizophrenia in the UK is 397 million pounds, or 1.6% of the total health care budget. Hospital-based and community-based residential care accounts for nearly three-quarters of these costs, while drugs account for only 5%. A conservative estimate of the indirect annual costs of lost production is in the region of 1.7 billion pounds. The heterogeneity of the disease and its outcome means that average treatment costs per person with schizophrenia should be treated with caution; 97% of direct costs are incurred by less than half the patients. Therefore, treatments which reduce the dependence and disability of those most severely affected by schizophrenia are likely to have a large effect on the total cost of the disease to society and may therefore be cost-effective, even though they appear expensive initially. PMID- 7865194 TI - Towards more effective antipsychotic treatment. AB - The development of antipsychotic drugs has followed two complementary approaches, either towards highly specific actions (e.g. on the dopamine receptor) or targeting a broad range of receptors. The properties of 'atypical' agents challenge the original dopamine hypothesis and suggest roles for a variety of dopamine receptors and for other pathways, such as serotonin. Older drugs, despite their proven efficacy in relieving many schizophrenic symptoms, have several drawbacks, being ineffective in some patients, relatively ineffective against negative symptoms, and causing adverse neurological effects which may, in turn, be associated with poor compliance. Among newer agents, currently available ones, such as clozapine and risperidone, offer the possibility of more effective control of negative symptoms and an improved side-effect profile, while others are in earlier stages of development. However, much still remains to be understood about their mechanisms of action. PMID- 7865195 TI - Neurodevelopmental schizophrenia: the rediscovery of dementia praecox. AB - Many people with severe schizophrenia have increased cerebral ventricular size and diffuse reduction in cortical volume; recent attention has focused on subtle malformations of the cytoarchitecture in the hippocampus and parahippocampal cortex. Sufferers also show an excess of dermatoglyphic and minor physical abnormalities, and a significant proportion had psychomotor deficits, cognitive or behavioural problems as children. Such findings suggest that the form of schizophrenia most akin to Kraepelin's original description of dementia praecox results from neurodevelopmental impairment. This may have its origin in genetic defects in the control of early brain growth, or in early environmental hazards such as prenatal exposure to maternal influenza or perinatal complications. How foetal or neonatal lesions produce hallucinations and delusions two or three decades later remains a mystery, but maturational changes in the brain may be important. PMID- 7865196 TI - [Antibiotic resistance: current problems and prospects]. AB - In recent years the frequency and spectrum of antibiotic resistant microorganisms have dramatically increased worldwide. In same cases certain infections turned out to be essentially untreatable with antimicrobial drugs. The antibiotic resistance and its transmissibility among different microorganisms poses serious problems for the near future. It is thus important to search and develop rapidly new antimicrobial drugs with improved activity and able to overcome resistance mechanisms. A more prudent and appropriate use of antimicrobial drug in humans and animals is also recommend. PMID- 7865197 TI - Biological accessibility of calcitonin and osteocalcin marked 125J for rats. AB - Biological accessibility of calcitonin and osteocalcin marked 125J for rast. In this study we estimated the biological accessibility and the degree of biological accessibility of calcitonin in relation to highly specific marker-osteocalcin after a single intraperitoneal administration. We showed mean values of biopharmaceutical parameters for the analysed hormones. PMID- 7865198 TI - Antibacterial evaluation of some xanthate derivatives and their diorganotin (IV) complexes. AB - The antibacterial activity of some xanthate derivatives K(SSCOR), where R = C6H5 (CyX), CH3NHCH2CH2-(MAEX), (CH3)2NCH2CH2-(DMAX), (CH3)2NCH2CH(CH3)-(DMAIX) and (C2H5)2NCH2CH2-(DEAEX) together with their diorganotin (IV) complexes R2Sn(SSCOR)2, where R' = Me, Bu(n), Ph, has been studied against eight species of bacteria in vitro. A significant activity against S. typhimurium was displayed by the xanthate derivative CyX and its complex Ph2Sn(CyX)2 at concentrations ranging from 1-10 micrograms/ml, and a remarkable activity was exhibited by the complexes Ph2Sn(CyX)2, Ph2Sn(MAEX)2 and Ph2Sn(DMAX)2 against P. aeruginosa at concentrations ranging from 0.1-10 micrograms/ml. By contrast, no such activity was demonstrated by the antibiotics used in this study (amoxicillin and chloramphenicol) against the same bacterial species. PMID- 7865199 TI - Communication among preschoolers with and without disabilities in same-age and mixed-age classes. AB - Communicative interactions of preschool children with and without disabilities in classrooms of same or mixed ages were compared. Sixteen children with developmental disabilities (most with mild or moderate mental retardation) and 32 children without disabilities between 1.5 and 4.5 years of age were randomly assigned at the beginning of the school year to either a same- or mixed-age grouping of 6 children. They were observed 6 months later interacting with classmates in a standard free-play environment. Results showed that children in mixed-age classes took more turns in conversations with partners with disabilities than did children in same-age classrooms. They also received more turns from their partners with disabilities, which were more often responses than initiations in the mixed-age as compared to same-age classes. In contrast, during communicative interactions with partners without disabilities, children in both types of classes did not significantly differ in number or types of turns. Children of a similar developmental level also had similar communicative interaction styles. PMID- 7865200 TI - Costs of family care for adults with mental retardation and related developmental disabilities. AB - "Out-of-pocket" spending by families supporting an adult family member with mental retardation or related developmental disability was characterized and estimated. Annualized nonreimbursed spending among a sample of 99 Chicago-area households was evaluated through survey and telephone interview across 10 categories of routine daily living expenses and disabilities-related services. The average annual out-of-pocket cost was $6,348. Average pre-tax income for the sample households was $37,657. Although wealthier households reported higher levels of spending, the percentage of household income represented by out-of pocket costs increased significantly as family incomes decreased. Results were discussed in the context of families as a focus for service planning and public policy and the importance of the family to the nation's system of care. PMID- 7865201 TI - Effect of parental acceptance or rejection of a proposed aversive intervention on treatment acceptability. AB - Effects of parental acceptance or rejection of a proposed aversive behavioral intervention on treatment acceptability ratings were investigated. Results suggest that parental acceptance or rejection of the proposed intervention significantly affected treatment acceptability ratings. The issue of a client's right to effective treatment versus the right to be free of a restrictive or aversive intervention was the dominant issue for judges. Results were discussed in terms of the usefulness of treatment acceptability ratings in treatment decision-making. PMID- 7865202 TI - Adult interaction style effects on the language sampling and transcription process with children who have development disabilities. AB - A determination was made of whether an empirically derived interaction style improves the usefulness of the language sampling and transcription in 17 children with developmental disabilities in Brown's (1973) Stages I and II. Whether the interaction style affected the diversity and complexity of the language the children produced during the samples was also examined. All subjects experienced two 20-minute interaction sessions that differed according to whether topic continuing wh-questions were used. Results indicated that, regardless of order of exposure to the styles, children talked more often and produced proportionally more transcribable utterances. In addition, they produced a larger sample of productive vocabulary in the style using topic-continuing wh-questions. There were no style effects on vocabulary diversity or length of utterance. The importance of using interaction styles that maximize the information available from language samples of young children with disabilities was discussed. PMID- 7865203 TI - Incidence of obesity among school children with mental retardation in Japan. AB - The incidence of obesity of children with mental retardation was determined in a sample of 20,031 pupils and students at special schools in Japan. The incidence was higher among girls than boys and in the junior and senior high departments (12 to 17 years) than in the elementary department (6 to 11 years). It was also higher among children with mental retardation of elementary and junior-high age than among children without mental retardation of the same age. The incidence of major diseases among obese children was also determined. PMID- 7865204 TI - Adaptation of Hispanic families to a member with mental retardation. AB - Adaptation of Hispanic (n = 51) and non-Hispanic (n = 195) white families to having a member with mental retardation was examined using surveys and interviews. We compared these families' demographic characteristics, religious values, and support resources and examined how these factors differentially affected caregiving burden for each group. Surveys and interviews were collected from 51 Hispanic and 195 non-Hispanic white families. Findings indicated that Hispanic families differed from the other families in SES, age of the person with mental retardation, religious values, and in their perceived burden of caring for a family member with mental retardation. Patterns of determinants of caregiving burden did not differ significantly for the two groups. PMID- 7865205 TI - Affective expressions of toddlers with and without Down syndrome in a social referencing context. AB - Affective expressions of 11 toddlers with Down syndrome and 11 toddlers with no disabilities were compared. Each child participated, with one parent, in a social referencing procedure. Children's MAs ranged from 12 to 23 months. Parents posed positive or fearful expressions during presentations of ambiguous stimuli. Lability and intensity of children's expressions and regulation of affect were noted. Expressions of toddlers with and without Down syndrome were equally labile and intense. However, toddlers without Down syndrome tended to match their parents' expressions. Toddlers with Down syndrome did not match their parents expressions; instead, they responded with positive affect following fearful parental communications. Results were discussed in terms of the impact of emotional predictability and responsivity on caregiving interactions. PMID- 7865206 TI - The questionnaires on resources and stress: what do they measure? PMID- 7865207 TI - Performance on the Penn Facial Discrimination Task by adults with mental retardation. PMID- 7865208 TI - Should our journals publish research sponsored by the tobacco industry? Introduction: the ethics of publishing research sponsored by the tobacco industry in ATS/ALA journals. ATS Bioethics Committee. PMID- 7865209 TI - Should our journals publish research sponsored by the tobacco industry? Pro: the search for untainted money. PMID- 7865210 TI - Should our journals publish research sponsored by the tobacco industry? Con: the smoking lamp should not be lit in ATS/ALA publications. PMID- 7865211 TI - Does gene therapy call for "STAT" immunity and inflammation at the epithelial barrier? PMID- 7865212 TI - Mucous and serous secretions of human bronchial epithelial cells in secondary culture. AB - Human bronchial surface epithelial cells were maintained in secondary culture on a collagen gel substrate in a defined, serum-free medium. These conditions have previously been reported to promote mucous cell differentiation. After 3 wk in culture, approximately 40% of the cells were stained by an antibody directed against human respiratory mucin. Analysis of media from cells cultured in the presence of the radioactive precursors [3H]glucosamine and [35S]sulfate revealed that the cells secreted high molecular weight glycoproteins with properties of typical respiratory mucins. In addition, hyaluronic acid and proteoglycans containing chondroitin sulfate and/or heparan sulfate glycosaminoglycans were identified in cell conditioned media. Finally, Western blot analyses showed that the cells secreted lysozyme and mucous proteinase inhibitor, proteins that are generally considered to be markers for submucosal gland serous cells. These results show that human bronchial cells from the surface epithelium in secondary culture secreted a range of glycoconjugates and proteins that were typical secretory products of both mucous and serous cells. PMID- 7865213 TI - ICAM-1 expression on bronchial epithelium after recombinant adenovirus infection. AB - Early experience with recombinant adenoviruses for gene transfer to airway epithelium suggests that these vectors are associated with the development of inflammation. The mechanisms for this are unclear, but previous work has shown that respiratory viruses can cause increased expression of intercellular adhesion molecule-1 (ICAM-1) on airway epithelial cells. We therefore hypothesized that recombinant adenoviruses may induce ICAM-1 expression and thereby facilitate the development of airway inflammation. To address this, primary cultures of human bronchial epithelial cells were examined for ICAM-1 expression by flow cytometry after infection with a serotype 5, E1/E3-deleted recombinant adenovirus containing the Escherichia coli LacZ reporter gene driven by the cytomegalovirus promoter (Ad.CMVlacZ). Compared with control cells, ICAM-1 expression was unchanged after infection with Ad.CMVlacZ, but increased after infection with wild-type adenovirus. Treatment of Ad.CMVlacZ-infected cells with interferon gamma (IFN) resulted in increased ICAM-1 expression, but to a lower level than that seen in cells treated with IFN alone, indicating that recombinant adenovirus infection blunted IFN-induced up-regulation of ICAM-1. Adhesion of human leukocytes to human bronchial epithelial cells was not increased after Ad.CMVlacZ infection, thereby excluding an ICAM-1-independent increase in leukocyte epithelial adhesion. The results for ICAM-1 expression were confirmed in vivo, as immunostaining of human bronchial xenografts infected with Ad.CMVlacZ revealed basilar epithelial staining with ICAM-1, but no increased expression on cells expressing beta-galactosidase. This study demonstrates that unlike other respiratory viruses, recombinant E1/E3-deleted adenovirus does not cause increased ICAM-1 expression on human bronchial epithelium in vitro or in vivo nor increased leukocyte adhesion in vitro. PMID- 7865214 TI - Inhibition of fetal calf serum-stimulated proliferation of rabbit cultured tracheal smooth muscle cells by selective inhibitors of protein kinase C and protein tyrosine kinase. AB - Severe chronic asthma is associated with structural changes in the airway wall including airway smooth muscle (ASM) hyperplasia. We have used cultured ASM cells isolated from rabbit trachealis as a model with which to investigate possible mechanisms of accelerated ASM growth to mitogenic stimuli. To elucidate the role that protein kinase C (PKC)- and protein tyrosine kinase (PTK)-dependent pathways play in the control of ASM mitogenesis, we have investigated the effect of reportedly selective inhibitors of PKC (3-[1-[3-(amidinothio)propyl]-3-indolyl]-4 (1-methyl-3-indolyl)-1H - pyrrole-2,5-dionemethanesulfonate [Ro31-8220] and 3-[1 (aminopropyl)indolyl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione acetate [Ro31 7549]) and PTK (alpha-cyano-3-ethoxy-4-hydroxy-5-phenylthiomethylcinnamamide [ST638]) on partially purified PKC, fetal calf serum (FCS)-stimulated protein phosphotyrosine content and on FCS-induced proliferation. Anion-exchange chromatography of lysed ASM cells resolved two peaks of Ca(2+)-activated, phospholipid-dependent PKC activity and one peak of Ca(2+)- and phospholipid independent PKC activity. The selective PKC inhibitors, Ro31-8220 and Ro31-7549, abolished the main peak of PKC activity and the Ca(2+)- and phospholipid independent peak that co-eluted with the main peak. The inhibition was dependent on the concentration of ATP in the reaction cocktail (IC50: 10 microM ATP: Ro31 8220 0.026 microM, Ro31-7549 0.073 microM; 100 microM ATP: Ro31-8220 0.065 microM, Ro31-7549 0.271 microM), consistent with these compounds inhibiting PKC at the ATP-binding site. Ro31-8220 was more potent (2- to 3-fold) than Ro31-7549. Concentrations of each inhibitor that produced maximal inhibition of the pooled kinase activity also abolished the second peak of Ca(2+)-dependent activity. The PTK inhibitor, ST638, had no effect on the kinase activity associated with any of the Ca(2+)-dependent or -independent peaks that eluted from the column. ST638, however, maximally inhibited FCS-stimulated PTK activity (IC50 25 microM). FCS stimulated PTK was also inhibited by Ro31-8220 (IC50 0.15 microM), but only by 60%, revealing an Ro31-8220-insensitive component to the response. The ability of each protein kinase inhibitor to inhibit proliferation was also studied using four independent indices of ASM cell growth and division: 3-(4,5-dimethylthiazol 2-yl)2,5-diphenyl tetrazolium bromide (MTT) dye conversion, Coomassie blue protein determination, hemacytometer cell counts, and DNA synthesis. Ro31-8220 and Ro31-7549 produced concentration-dependent inhibition of FCS-stimulated proliferation of growth-arrested ASM cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7865215 TI - Chrysotile asbestos stimulates platelet-derived growth factor-AA production by rat lung fibroblasts in vitro: evidence for an autocrine loop. AB - We have investigated the mitogenic and chemotactic role of platelet-derived growth factor (PDGF) in pulmonary fibrogenesis induced by chrysotile asbestos. Since fibroblasts phagocytize asbestos in the lung interstitium, we have sought to learn whether the fibers alter the production of PDGF-like molecules by rat lung fibroblasts or induce mitogenesis of these fibroblasts in vitro. Conditioned medium as well as cell lysates from fibroblasts exposed to asbestos contained approximately 4-fold more PDGF than unexposed cells as detected by Western blot. Two distinct molecular weight forms of PDGF (36 and 18 kD) were detected by Western blotting. We postulate that these PDGF-like molecules are homologues of human PDGF-AA since we could not detect any PDGF in a sensitive enzyme immunoassay that recognized only PDGF-BB and PDGF-AB. Furthermore, PDGF-A chain mRNA was readily detected by Northern analysis, whereas PDGF-B chain mRNA was not detected by conventional Northern analysis. However, message amplification using a reverse transcriptase polymerase chain reaction allowed detection of the B chain message. A significant dose-dependent mitogenic effect of asbestos was found by using both a cell proliferation assay and nuclear labeling with bromodeoxyuridine when fibroblasts were exposed under serum-free conditions. This mitogenesis induced directly by asbestos was blocked almost entirely with an anti PDGF antibody that neutralized all three PDGF isoforms. Thus, these data support our hypothesis that an autocrine loop for PDGF-AA is operative in vitro following exposure to asbestos in lung fibroblasts, and we suggest that this signaling pathway could be significant in the pathogenesis of pulmonary fibrosis. PMID- 7865216 TI - Hyperoxic suppression of Fc-gamma receptor-mediated phagocytosis by isolated murine pulmonary macrophages. AB - Lower respiratory tract exposure to high oxygen (O2) concentrations is known to induce changes in pulmonary function through effects on several cell types located within the lung parenchyma, including pulmonary macrophages (PM). We studied the effects of hyperoxic exposure on phagocytosis via Fc-gamma receptors (FcR) on isolated murine PM. PM cultured in hyperoxic conditions exhibited little change in ingestion via FcR for up to 96 h, compared with significant increases in ingestion by PM cultured in 21% O2 over the same time period. This suppression was reversible and occurred whether 50 or 100% O2 concentrations were used for hyperoxic exposure. Addition of the potent macrophage-activating agent interferon gamma (IFN-gamma) to cultured PM further increased FcR-mediated phagocytosis in normoxic PM but had no effect on PM cultured in 100% O2. Analysis of FcR expression by flow cytometry using monoclonal antibodies specific for two different FcR classes revealed that culture in normoxic conditions increased surface expression of both FcR classes. Hyperoxic culture inhibited up-regulation of the high-affinity FcR but did not affect low-affinity FcR up-regulation, suggesting that hyperoxic effects were not due solely to effects on regulation of FcR expression. However, hyperoxic exposure completely suppressed FcR-mediated actin polymerization. These findings suggest that hyperoxic exposure impairs PM ability to increase FcR-mediated phagocytic activity after appropriate stimulation, which could impair the lung's defenses against infection. PMID- 7865217 TI - Tumor necrosis factor-alpha induces mucin hypersecretion and MUC-2 gene expression by human airway epithelial cells. AB - Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional, proinflammatory cytokine that is capable of activating a diverse number of target genes within multiple cell types. Little information is known regarding the role of TNF-alpha in the regulation of human airway mucin hypersecretion and MUC-2 gene expression. To assess the effect of TNF-alpha exposure on mucin secretion, human airway organ cultures and primary cultures of human airway epithelial cells were stimulated with 20 ng/ml of recombinant human TNF-alpha and mucin secretion quantitated by an enzyme-linked immunosorbent assay using a specific monoclonal antibody directed against human airway mucin. Significant increases in mucin secretion from human airway organ cultures were initially detected at 1 h, peaked at 8 h, and persisted for 24 h. The TNF-alpha-mediated mucin hypersecretion at 8 h was concentration dependent. Significant increases in mucin secretion from primary cultures of human airway epithelial cells were initially detected at 4 h, peaked at 48 h, and persisted for 72 h after stimulation with 20 ng/ml of recombinant human TNF-alpha. The TNF-alpha-mediated mucin hypersecretion at 48 h from primary cultures of human airway epithelial cells was inhibited by coincubation with soluble 55 kD, type I TNF receptors. Using reverse transcription-polymerase chain reaction and a human pulmonary mucoepidermoid carcinoma cell line (NCI-H292), increases in MUC-2 steady-state mRNA levels were first detectable after 30 min of TNF-alpha stimulation and persisted for 24 h. Cycloheximide did not inhibit TNF alpha-mediated MUC-2 mRNA expression at 1 h, suggesting that new protein translation was not required.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865218 TI - Potent inhibition of both human interferon-gamma production and biologic activity by the Clara cell protein CC16. AB - The Clara cell 16 kD protein (CC16), the predominant product of the Clara cells lining the bronchiolar epithelium, is thought to protect the respiratory and urogenital tract from unwanted inflammatory reactions through its immunosuppressive action. In this report, we show evidence that CC16 establishes an anti-inflammatory activity by interfering with the interferon-gamma (IFN gamma)-mediated actions of the cytokine network. The HuIFN-gamma production of stimulated single-donor peripheral blood mononuclear cells is inhibited by the presence of doses of CC16 in the range of 10(-12) M, with a maximal inhibition (up to 95%) when interleukin-2 is used as a stimulating agent. CC16 also diminishes the biologic activity of IFN-gamma: both the antiviral activity and the stimulation of phagocytosis by IFN-gamma, measured by means of chemiluminescence, are reduced in the presence of CC16. These observations indicate that CC16 acts as an anticytokine and could give new insight in the potential role of the Clara cells. PMID- 7865219 TI - Cl(-)-HCO3- exchanger isoform AE2 is restricted to the basolateral surface of alveolar epithelial cell monolayers. AB - We investigated the polarized distribution and isoform specificity of anion exchange (Cl(-)-HCO3- exchange) in alveolar epithelial cell monolayers. Rat alveolar type II epithelial cell monolayers were grown in primary culture on detachable tissue culture-treated nuclepore filters. Each filter was mounted in a cuvette containing two fluid compartments (apical and basolateral) separated by the monolayer, the cells loaded with pH-sensitive dye, and intracellular pH (pHi) measured spectrofluorometrically. To assay for Cl(-)-HCO3- exchange, monolayers were incubated in medium containing 24 mM HCO3-/5% CO2 and 140 mM NaCl at pH 7.4 and acutely alkalinized by replacement of the fluid by HCO3(-)-free buffer containing Hepes (6 mM) at pH 7.4. Monolayers exhibited basolateral (but not apical) Cl(-)-dependent, Na(+)-independent recovery from an alkaline load that was abolished when Cl- was substituted by equimolar gluconate in the basolateral fluid, or if DIDS (500 microM) was present basolaterally. Substitution of gluconate for Cl- in the basolateral fluid, but not the apical fluid, resulted in a rise in steady-state pHi that was reversible on replacement of the basolateral fluid with Cl(-)-containing buffer, which occurred in HCO3(-)- but not Hepes buffered medium. These data indicate that alveolar epithelial cells express basolateral membrane domain of these cells. Northern analysis of alveolar epithelial cell mRNA using anion exchanger (AE) isoform-specific cDNA probes indicates that alveolar epithelial cells express the AE2 isoform predominantly, if not exclusively, and do not express detectable AE1 (i.e., band-3 protein) or AE3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865220 TI - Hydroxyl radical production and lung injury in the rat following silica or titanium dioxide instillation in vivo. AB - The hydroxyl radical (.OH) is a highly reactive oxygen free radical that has been implicated as a cause of lung injury following exposure to silica and silicates. Despite evidence that silica generates .OH in vitro, there has been no previous demonstration of in vivo production of .OH after exposure to nonfibrous mineral oxide dusts. We tested the hypothesis that instillation of silica into rat lungs is associated with greater .OH production and acute lung inflammation in vivo relative to the instillation of a less toxic nonsilicate particle, titanium dioxide. The production of .OH in the lungs following dust instillation was measured using sodium salicylate as an .OH trap. Seven days after dust exposure, the rats were given intraperitoneal salicylate, the lungs isolated, and salicylate hydroxylation products (2,3- and 2,5-dihydroxybenzoic acid), reflecting .OH, were measured. There was significantly more 2,3-dihydroxybenzoic acid in silica-exposed lungs compared with lungs instilled with titanium dioxide. In addition, the instillation of silica into rat lungs in vivo was associated with a greater acute inflammatory response. We conclude that following in vivo exposure, silica stimulates greater .OH production relative to the less toxic particle, titanium dioxide. These differences in .OH generation correspond to disparities in acute lung inflammation. PMID- 7865221 TI - Macrophage engulfment of apoptotic neutrophils contributes to the resolution of acute pulmonary inflammation in vivo. AB - For resolution of inflammation to occur, it is necessary both to limit leukocyte influx and to clear now redundant cells from the tissues. Recent evidence from in vitro studies suggests that clearance may be an active process, accomplished in part by macrophage engulfment of intact cells that have undergone programmed cell death or apoptosis. However, the kinetics of these events and their association with the resolution of acute inflammatory responses in vivo remain to be elucidated. To investigate these events, we examined an animal model of acute, limited, neutrophilic pulmonary inflammation. Cells were obtained by bronchoalveolar lavage (BAL) of rats at various time points after intratracheal administration of lipopolysaccharide (LPS). Apoptotic neutrophils were rarely seen in BAL from control animals but were detected after neutrophil influx had occurred in response to LPS challenge. Macrophage engulfment of these cells was identified at light microscopy and confirmed at electron microscopy. The proportion of macrophages that had engulfed apoptotic neutrophils was maximal 24 h after LPS challenge and declined thereafter as total neutrophil numbers fell. During the resolution phase, the alveolar macrophages became positive for peroxidase, indicating the presence of neutrophil granule contents in their cytoplasm. These observations demonstrate that apoptosis of leukocytes indeed occurs during the course of an acute inflammatory response in vivo and that the emergence of apoptotic neutrophils and macrophage engulfment of these cells are temporally correlated with the resolution of acute inflammation. PMID- 7865222 TI - Analysis of fused-membrane structures in bronchoalveolar lavage fluid from patients with alveolar proteinosis. AB - Alveolar macrophages of patients with alveolar proteinosis, obtained by lung lavage, contain a large number of intracytoplasmic inclusions with mutlilamellar membranous structures, called fused-membrane structures, having a periodicity of 4.7 nm. To analyze the composition of these structures, we concentrated them from the bronchoalveolar lavage fluid of patients by a combination of sucrose density gradient ultracentrifugation and enzyme hydrolysis using proteinase K. Fused membrane structures were most numerous (26.2%) in a fraction obtained at the interface between 1.0 and 1.1 M sucrose solutions separated after proteinase K hydrolysis. This fraction was rich in acidic phospholipids. Hydrophobic surfactant apoproteins constituted about 77% of the proteins in this fraction, and a remarkable increase in the content of surfactant-associated protein C (SP C) was found. The phospholipid-to-protein ratio was 0.25:1. Based on these results, we tried to reconstitute fused-membrane structures from purified lipids and hydrophobic proteins isolated from the patients' lavage fluid or from pig lungs. Only in the presence of both phospholipids and SP-C were similar multilamellar structures, having a periodicity of 4.3 to 4.5 nm, formed. These results suggest that fused-membrane structures have a close relationship to a hydrophobic surfactant-associated protein, SP-C, which accumulates in alveolar macrophages, possibly by incomplete digestion. PMID- 7865223 TI - [XLVI Annual meeting of the Spanish Society of Neurology. Barcelona, 7-10 December 1994. Abstracts]. PMID- 7865224 TI - Dosimetry of irradiation models. The 96-well clonogenic assay for testing radiosensitivity of cell lines. AB - Radiation experiments with cells in single cell suspension in test tubes and on 96-well plates were carried out and compared. The cells originated from cell lines established from carcinomas of the floor of the mouth and from endometrial carcinoma. Two irradiation models were constructed. Both models allowed the absorbed doses to the cells to be administered with a high accuracy in both experimental settings (better than 5.0%). These irradiation models were compared on cancer cell lines with dissimilar inherent radiation sensitivity and histologic type (UM-SCC-1 resistant, UM-SCC-14A sensitive, and UT-EC-2B highly sensitive); various radiation doses were used. The fractions of surviving cells as a function of radiation dose were compared: there was no significant difference between cells irradiated in test tubes and cells irradiated in 96-well plates. Thus, if the absorbed doses in cells suspended in a tube and in a plate were the same, the survival was similar regardless of the type of irradiation model. PMID- 7865225 TI - DNA damage in human endothelial cells after irradiation in anoxia. AB - Endothelial cells and fibroblasts have been reported to respond differently to oxidative stress. Both the effects of high oxygen tension and radiation involve the action of free radicals. DNA damage (single strand breaks, SSB, and double strand breaks, DSB) was assayed in human umbilical cord vein (HUV) cells and in Chinese hamster fibroblasts (V79) after irradiation under oxic or anoxic conditions. The cells were exposed to single doses in the range of 2-18 Gy of gamma-radiation from 60Co. Significantly more DNA damage was induced in the V79 cells than in the HUV cells. As a consequence, a higher oxygen enhancement ratio was obtained for the HUV cells (6.3) as compared to the V79 cells (2.8). The repair of SSB was slower in the HUV cells than in the V79 cells, irrespective of oxic state. For the higher doses, the damage remaining at 60 min after anoxic irradiation, i.e. DSB, was only detected in the V79 cells. PMID- 7865226 TI - Pleurodesis with doxycycline or Corynebacterium parvum in malignant pleural effusion. AB - Pleurodesis with doxycycline (100 mg and 600 mg) and Corynebacterium parvum (1 mg and 7 mg) were compared in 41 patients with malignant effusion. To evaluate the mechanisms, pleural fluid pH, leukocytes, granulocytes, interleukin-6 (IL-6) and serum IL-6, as well as C-reactive protein (CRP) were measured before and on 2 consecutive days after treatment. Corynebacterium parvum produced a greater acute phase response measured with fever, serum CRP and IL-6 than doxycycline. However, no change in pleural fluid IL-6 was demonstrated. Among the 35 assessed patients, 26 had objective response, similar in all four treatment groups. Side-effects were more common with Corynebacterium parvum. Based on this preliminary study we conclude that doxycycline, even in low doses, is a highly effective and well tolerated agent for palliative treatment of malignant pleural effusion. As the responses were similar despite different inflammatory reactions, the two agents probably induce pleural obliteration through different mechanisms. PMID- 7865227 TI - Combined chemotherapy, radiotherapy and surgery in inflammatory breast carcinoma. PMID- 7865228 TI - Ovarian cancer--not every abdominal mass is a recurrence. PMID- 7865229 TI - Is coronary artery disease associated with radiotherapy preventable by salicylates? PMID- 7865230 TI - p53 protein expression in leukemias. AB - p53 protein expression has been investigated by immunohistochemistry in 58 patients with leukemia. Seven of 24 cases with acute myeloid leukemia (AML), 3 of 15 cases with chronic lymphocytic leukemia (CLL), one of 11 cases with chronic myeloid leukemia (CML) and 4 of 8 cases with acute lymphoid leukemia (ALL) had p53 protein expression. Of patients having p53 expression, one case with AML had refractory anemia with excess blasts-transformation (RAEB/t), one case with CLL had Richter's syndrome and another one with CML was in accelerated phase. Finally, 26% of leukemia cases had p53 protein expression. It may be concluded that p53 protein abnormalities may have an important role in leukomogenesis and in the development of more malignant clones in chronic leukemias. PMID- 7865231 TI - Detection of structural aberrations of chromosome 17 in malignant gliomas by fluorescence in situ hybridization (FISH). AB - Isolated nuclei prepared from fresh-frozen tissue specimens were used to investigate structural aberrations of chromosome 17 in 18 malignant gliomas (7 anaplastic astrocytomas, 11 glioblastomas). Nuclear DNA was hybridized with four DNA probes specific for centromeric (D17ZI), telomeric (Tel 17p, Tel 17q) and 17p 13.1 sequences (p53) of chromosome 17, using fluorescence in situ hybridization (FISH). The rates of nuclei with one signal (OS) for Tel 17p and p53 were significantly higher than those for D17ZI and Tel 17q. This indicated that the majority of chromosome 17 aberrations was a deletion of the short arm including the p53 gene. When compared with the histological grading, the rates of OS for Tel 17p and p53 in anaplastic astrocytomas were higher than those of glioblastomas, suggesting that the deletion may be associated with the early events in tumorigenesis and that some glioblastomas without chromosome 17 aberrations may be independent from tumour progression via low-grade gliomas. PMID- 7865232 TI - The nature of cancer: morphogenesis and progressive (self)-disorganization in neoplastic development and progression. AB - The aberrant forms of life, neoplasia and cancer, are discussed under the events at the beginning of neoplasia and under five classes of neoplastic lesions. The lesional classes are: 1) The precursor state; 2) Intermediate lesions; 3) Primary cancer; 4) Metastasis; and 5) Metastasis from metastasis. The events at the beginning are a diverse group of agents and mechanisms that induce the lesions of the precursor state, not cancer. The lesions and events produced by induction are similar regardless of the agent. Thus, there must be similar biological principles and mechanisms operative in different neoplastic systems. The classes of neoplastic lesions and cancer are described and a theory derived therefrom. The theory is: Any perturbation that alters a cell or group of cells and their stroma so that they no longer respond appropriately to the forces of tissue, organ, and organismal maintenance, may induce a neoplastic system. The sequential progression of lesions of the induced neoplastic system is the result of a successive series of flaws in the continuum of reciprocal interactions between a group of cells and their stroma. The flaws, appearing seriatim, produce progressive (self)-disorganization of the lesions and progressive loss of response to the forces of tissue and organ maintenance. PMID- 7865233 TI - Core needle aspiration biopsy of palpable breast masses. AB - The purpose of the present study was to determine the usefulness of core needle aspiration biopsy (CNAB) with an 18-gauge modified menghini needle in the preoperative evaluation of 145 palpable breast masses as the major indicator for definitive treatment by surgery. Of the 145 lesions histologically verified by surgery, 126 were diagnosed as carcinoma, of which 117 were correctly diagnosed by the needle biopsy (93%). CNAB showed a sensitivity of 90% in the diagnosis of breast malignancy and a specificity of 100%. The overall diagnostic accuracy was 91%. There were no false-positive results and after definitive diagnosis with the Menghini needle, a one-stage procedure without frozen sections could be performed for definitive treatment of breast carcinoma. PMID- 7865234 TI - The expression of glutathione transferase isoenzymes in human malignant lymphoma biopsies. AB - Glutathione transferase (GST) activity as well as the expression of different classes of GST isoenzymes were studied in 14 lymphoma biopsies. The GST activity measured with 1-chloro-2,4-dinitrobenzene as a substrate, varied almost 9-fold. The expression of GSTs classes Pi, Alpha and Mu was studied by immunoblotting using antibodies against human GSTs. All lymphoma samples displayed high levels of class Pi GST. Class Alpha and Mu GSTs expression varied from not detectable to high. The observations were confirmed by quantitation of the three classes of GST with an ELISA technique. Nine of the patients were treated with bifunctional alkylating agents. A correlation between a clinical complete response to chemotherapy and low expression of GST Alpha was noted (p < 0.02). PMID- 7865235 TI - Metastases in cases with hepatocellular carcinoma in relation to clinicopathologic features of the tumor. An autopsy study from a low endemic area. AB - In order to study clinicopathologic features of hepatocellular carcinoma (HCC) and their relation to metastatic growth, all autopsied cases with confirmed HCC (n = 490) from a period with a high autopsy frequency in a well-defined population were analyzed. Cirrhosis, usually of micronodular type, was found in 72%. The gross appearance of the tumour was predominantly massive (46%) or multinodular (42%). The tumour involved both liver lobes in 72% or the right lobe alone in 20%. Histologically, trabecular growth (79%) and grade II of differentiation (52%) prevailed. Vascular invasion was noted in 56%, whereas involvement of the biliary tract was unusual (4%). Metastases especially involved lymph nodes (42%), lungs (18%) and skeleton (17%). Increased weight of the liver, multinodular appearance, involvement of both liver lobes, low grade of differentiation and vascular invasion were significantly associated with presence of metastases. PMID- 7865236 TI - Heat-stable alkaline phosphatase. A putative tumor marker of head and neck squamous cell carcinoma. AB - Serum total alkaline phosphatase (AP) activity and heat-stable AP (HSAP) were investigated in patients with uncontrolled squamous cell carcinoma of the head and neck before and after treatment. No significant differences in AP activity were seen between normal subjects and cancer patients. However, the HSAP fraction of the total AP activity was significantly elevated prior to treatment and the level declined and remained low during successful treatment, while it increased with tumor progression or recurrences. Heat-stable AP was found to be a useful tumor marker of potential usefulness in the management of patients with squamous cell carcinoma of the head and neck. PMID- 7865237 TI - Biochemical parameters as prognostic factors in prostatic adenocarcinoma. AB - The serum levels of creatinine (CR), alkaline phosphatase (ALP), acid phosphatase (ACP) and tartrate inhibitable acid phosphatase (TIAP) were related to Gleason score, TM-category, disease progression and survival in 325 prostatic adenocarcinoma patients followed up for over 12 years. Elevated serum levels of CR, ALP, ACP and TIAP were related to invasive and metastatic disease as well as with a high Gleason score. Elevated serum levels of CR, ALP, ACP and TIAP, all significantly predicted prognosis in a univariate analysis. In the M0 tumours, ACP and TIAP and TIAP had prognostic value, as they did in the T1-2M0 tumours respectively. Cox's multivariate analysis showed that serum creatinine level at diagnosis had independent prognostic value additional to the TM-classification, Gleason score and patient age. In the M0 tumours, ALP had independent prognostic significance additional to the T-category, Gleason score and patient age. In the T1-2M0 tumours, TIAP had independent prognostic value supplementary to the Gleason score, T-category and patient age, whereas in the T1M0 tumours, the gleason score was an independent prognostic parameter. The results indicate that these simple laboratory tests give important prognostic information in prostatic adenocarcinoma. PMID- 7865238 TI - Urinary excretion of pseudouridine and prognosis of patients with malignant lymphoma. AB - Urinary excretion of pseudouridine, a modified nucleoside, was assessed in 30 patients with Hodgkin's disease, and 106 patients with non-Hodgkin's lymphoma, classified according to the Kiel system. Elevated excretion was found in 47% of 49 patients with high-grade malignant (HGM) lymphoma, and in 37% of 57 with low grade malignant (LGM) lymphoma, in 13% in Hodgkin's disease, and 3% in 79 reference individuals. The level of pseudouridine excretion correlated with clinical stage in HGM lymphoma (p < 0.0001), but not in LGM lymphoma or Hodgkin's disease (p = 0.086 and 0.36 respectively). Of 28 patients with B-symptoms 71% had elevated excretion, compared to 26% of 108 without B-symptoms (p < 0.0001). Elevated excretion of pseudouridine before therapy was associated with shorter survival time in LGM lymphoma stage II to IV disease, (p = 0.022), and a similar tendency was also observed in HGM lymphoma. Using Cox proportional hazard model, age, malignancy grade, excretion of pseudouridine, and disease stage were identified as independent prognostic factors in non-Hodgkin's lymphoma. PMID- 7865239 TI - Malignant lymphoproliferative diseases in HIV-seropositive patients. A study of 40 cases at a single institution in Spain. AB - We identified 40 patients with malignant lymphoproliferative diseases (MLD) and HIV infection (seropositive) at a single Spanish university hospital. Thirty-two patients had non-Hodgkin's lymphoma (NHL), 6 primary central nervous system lymphoma (PCL) and 8 patients Hodgkin's disease (HD). Median age at presentation was 32 years. Four histopathological groups had distinct presenting clinical features: in 93% of the Burkitt-type lymphomas, the lymphoma itself was the AIDS defining criterion, while high and intermediate grade NHL other than Burkitt-like tended to have a more advanced HIV infection, demonstrated by antecedent AIDS criteria in 58% of these patients and a median CD4 positive cell count of 291 mm3; HD occurred in some patients without previous opportunistic infections (7/8 patients) but with median CD4 cells of 105 mm3; PCL occurred in a terminal stage of HIV infection, in patients with a low performance status, and frequent antecedent AIDS criteria. Objective response to chemotherapy could be seen in 62% of NHL patients and 100% of HD. Survival was adversely related to an antecedent diagnosis of AIDS, low performance status, and a primary localization in the central nervous system. Overall median survival was 5 months, but patients without the mentioned three adverse prognostic factors had a median survival of 10 months. PMID- 7865240 TI - Changes of blood viscosity in patients treated with 5-fluorouracil--a link to cardiotoxicity? AB - Cardiotoxicity is a serious but relatively unknown side-effect of treatment with 5-fluorouracil (5-FU). The underlying mechanism of 5-FU cardiotoxicity has not been defined. The aim of the present study was to determine whether hemorheological factors might in part explain 5-FU cardiotoxicity. Changes of blood and plasma viscosity, fibrinogen and hematocrit were studied in 11 patients treated by 5-FU. The study showed a decrease in blood and plasma viscosity during treatment with 5-FU, probably caused by a decrease of plasma fibrinogen. Reversible cardiotoxic effects were demonstrated in four patients. PMID- 7865241 TI - Full dose CHOP chemotherapy in elderly patients with non-Hodgkin's lymphoma. AB - Twenty-eight previously untreated elderly patients (median age 73 years, range 65 88) with aggressive non-Hodgkin's lymphoma were treated with full-dose CHOP chemotherapy between 1989 and 1992. The median of the average relative dose intensity (ARDI) was calculated for the initial cycles needed to achieve a maximal response or to determine progression of disease (1-6 cycles, median 4), as well as for the whole treatment course. For patients aged 65-74, both ARDIs were 0.89. A comparable group of 36 elderly patients who received reduced doses of CHOP from the start, served as a historical control. There was an increase of 11% and 29% in the ARDIs of the full-dose CHOP as compared with the reduced CHOP, in the initial cycles and for the whole treatment course respectively. Grade III IV leukopenia was the main toxicity observed in 57% of the patients, and 7 patients were hospitalized for fever and leukopenia. There was no treatment related death. It is concluded that CHOP chemotherapy without initial dose reduction is feasible in patients aged 65-74 years, resulting in high actual dose intensity with a reasonable degree of toxicity. PMID- 7865242 TI - Simultaneous cisplatin and radiation in endometrial adenocarcinoma cell lines. AB - The effects of concomitantly administered cisplatin and radiation were evaluated in four recently established endometrial adenocarcinoma cell lines. We used the 96-well clonogenic assay to obtain survival data which were fitted to the linear quadratic model. The area under the survival curve (AUC) was obtained by numerical integration. It turned out that there was only a systematic additive cytotoxic effect and no supra-additive, true radiosensitising effect could be found. The results were not affected by the cisplatin dose used, the intrinsic radiosensitivity of the cell lines or the sensitivity of the cells to cisplatin. PMID- 7865244 TI - Esthetic dentistry goes global. PMID- 7865243 TI - Salvage radiotherapy following chemotherapy failure in Hodgkin's disease--what is its role? AB - Radiotherapy is rarely used as salvage therapy following chemotherapy failure in Hodgkin's disease. Analysis of our experience identified only 11 cases from over 400 patients treated, and data from other centres are similarly sparse. Three (43%) of 7 patients with relapse confined to nodal sites were salvaged with radiotherapy alone. Actuarial relapse free survival at 5 years was 27% (+/- 12 SE) with survival 45% (+/- 15 SE). These data were then combined with four other detailed series in the literature to delineate the patient and disease characteristics of 60 patients, and better assess the role of salvage radiotherapy. This confirms that radiotherapy has an important role in salvaging a small proportion of cases, who can be spared the risk of more aggressive regimens, such as high dose chemotherapy. Patients with relapse confined to one or two nodal sites, and having a disease free interval greater than 12 months, have the best prospects for salvage. Initial stage IV disease seems to have little bearing, provided relapse is confined to nodal sites. PMID- 7865245 TI - Improving the precision of esthetic ceramic margins: guidelines for success. PMID- 7865246 TI - Esthetic considerations for the generalist in the preadolescent orthodontic patient. Part II: Evaluation and treatment of skeletal discrepancies. PMID- 7865247 TI - Reducing the adverse effect of bleaching on composite-enamel bond. PMID- 7865248 TI - The frictional-fit periodontal prosthesis: innovative esthetic and functional solutions to an old problem. PMID- 7865249 TI - New esthetic concepts in Oriental facial contouring. PMID- 7865250 TI - In vitro and in vivo evaluation of a new universal composite resin. PMID- 7865251 TI - Measurement of physical attractiveness: truth-of-consensus. PMID- 7865252 TI - Monitoring and sudden infant death. PMID- 7865253 TI - Rare disease surveillance. AB - Rare diseases in children account for disproportionate morbidity and mortality and are particularly demanding of both families and health resources. Surveillance may provide data on their epidemiology, aetiology, management and outcome and on the support requirements of affected children. Existing methods for rare disease surveillance include mandatory and voluntary notification schemes, which may be active or passive, hospital discharge databases and death certification data. The recent establishment of the Australian Paediatric Surveillance Unit has facilitated active, prospective, national case ascertainment by voluntary notification of selected rare conditions. Information obtained should enable estimation of incidence rates, evaluation of prevention and management strategies, extend data collected by existing methods and help estimate future health needs. PMID- 7865254 TI - Doing the undoable: narrowing the gap between paediatric training and paediatric practice. PMID- 7865255 TI - Antimicrobial factors and microbial contaminants in human milk: recent studies. AB - An overview of recent studies of antimicrobial factors and microbial contaminants found in human milk is presented. The incidence of gastrointestinal and respiratory infections in infants receiving human milk continues to be lower than in those not breast-fed due to the presence of specific antibody and possibly anti-adhesion factors in the milk. Whether the many other antimicrobial factors, which have been shown to be active in vitro or in animal model systems, have any influence on infant infections is still not clear. Microbial contaminants in human milk are rare, as are associated infant infections from the milk. However, some contaminants such as cytomegalovirus are commonly transferred to infants from the milk of seropositive mothers, fortunately without any adverse effects in the infants. Human T-lymphotropic virus type 1 is transferred via human milk in endemic areas, human milk being the main source of mother-to-infant transmission. While some reports suggest human immunodeficiency virus type 1 transfer may occur through human milk, this is not the predominant mode of transmission to infants. PMID- 7865256 TI - Revised statement on the relationship between dietary folic acid and neural tube defects such as spina bifida. National Health and Medical Research Council. PMID- 7865257 TI - Survey on developmental-behavioural training experiences of Australian paediatric advanced trainees. AB - In order to monitor whether paediatric education has adapted to meet modern practice 91 paediatric advanced trainees were surveyed to elicit their satisfaction with developmental-behavioural (DB) training. A response of 69% was obtained to a postal questionnaire. The traditional imbalance persists, with trainees considering themselves significantly better informed in the medical disciplines (P < 0.001). Satisfaction with training in the 14 developmental disciplines surveyed is less (P < 0.001) and significantly more variable compared with 11 traditional medical disciplines (P < 0.01). Formal rotations in DB disciplines had been received by all respondents by the 7th year of training. However, 46-67% consider themselves ill-informed in learning/school problems, attention-deficit hyperactivity disorder, adolescent problems, paediatric rehabilitation and language impairment. Thirty-seven per cent found formal postgraduate instruction unhelpful. Paediatric advanced training gives exposure to, but unsatisfactory formal education, in developmental and behavioural paediatrics. Current initiatives for mandatory DB training have serious implications for achieving adequate resources and standards to meet clinical and training demands. PMID- 7865258 TI - Factors adversely associated with breast feeding in New Zealand. AB - Control data from 1529 infants studied in a multicentre case-control study of sudden infant death in New Zealand were analysed to identify factors that might hinder the establishment and duration of breast feeding. Although 1300 infants (85%) were exclusively breast-fed at discharge from the obstetric hospital, this fell to 940 (61%) by 4 weeks. Logistic regression was used to identify factors that might adversely influence breast feeding 'at discharge', 'at 4 weeks' and the overall 'duration' of breast feeding. When adjusted for confounding factors, not exclusive breast feeding 'at discharge' was significantly associated with: twin pregnancy, being a Pacific Islander, mother not bedsharing, subsequent dummy use, birthweight less than 2500 g, heavy maternal smoking, not attending antenatal classes and mother less than 20 years old at first pregnancy. Mothers smoking more than 20 cigarettes a day were nearly twice as likely to not exclusively breast feed on discharge compared to those who did not smoke. A 'dose response' was apparent with the heaviest smokers having the least likelihood of establishing exclusive breast feeding. Being exclusively breast-fed at discharge but not 'at 4 weeks' was associated with: twin pregnancy, admission to a neonatal intensive care unit, subsequent dummy use and not being married. A shorter overall 'duration' of breast feeding was associated with maternal smoking, subsequent dummy use, mother not bedsharing, twin pregnancy, mother less than 20 years old at first pregnancy, low occupational status and not attending antenatal classes. These effects persisted when social and demographic factors, including birthweight, were taken into account.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865259 TI - Insulin-dependent diabetes mellitus in southern Chinese children: an overview. AB - Thirty-three southern Chinese children with insulin-dependent diabetes mellitus (IDDM) were studied. The patients had a mean follow-up of 5.2 years (range 1.2 8.2). The mean age of onset was 8.3 years (range 1.7-13.5). The mean duration of symptoms before diagnosis was 22 days. Ten patients (30%) presented with diabetic ketoacidosis at diagnosis. Only one patient (3%) was found to have thyroid microsomal antibodies and none was found to have hypothyroidism or hyperthyroidism. Incidence and prevalence were calculated from data recorded retrospectively and prospectively in a population-based registry of IDDM. The prevalence in 1991 and 1992 was 8.3 per 100,000 children under 15 years of age. The age-standardized incidence of IDDM was 1.7/100,000 per year with the 95% confidence interval of 1.2-2.4/100,000 per year for children under 15 years of age during the years 1986-93. The incidence for males was 1.1/100,000 per year and for females, 2.4/100,000 per year. PMID- 7865260 TI - Integrated health and education input in the development of educational resources about asthma for schools. AB - The development of educational packages on health-related topics has become common in school curricula. This paper describes an integrated health and education input in the development of an educational package about asthma for Year 8 high school students. Ownership and educational relevance of the package (ensuring its appropriateness for inclusion within the Personal Development/Health/Physical Education curriculum) was achieved by collaboration between teachers with an understanding of the principles of curriculum design and health professionals with content knowledge about asthma. The model used for the production of the package about asthma could be extended to other health topics. PMID- 7865261 TI - Myoclonic encephalopathy of infancy: a 10 year review. AB - Myoclonic encephalopathy of infancy (MEI) is a unique cause of acute ataxia in infants and is a rare presentation of neuroblastoma. Five cases presenting to a tertiary referral children's hospital during a 10 year period are reviewed. Two cases were associated with a neuroblastoma. All children were treated with intramuscular injections of adrenocorticotropic hormone, with symptomatic improvement. One child died from an opportunistic infection following chemotherapy for neuroblastoma. The four survivors have mild to moderate clinical and intellectual deficits. Investigation and continuing observation for occult neural crest tumours is emphasized for all cases of MEI, though no underlying cause was found in 60% of children in this study. PMID- 7865262 TI - Hospitalization of infants for infections in Western Australia, 1980-91. AB - Rates of hospitalization of Aboriginal infants in Western Australia from 1980 through 1991 for infections were much higher than for other infants and were consistently higher in rural areas than in metropolitan areas. There were substantial declines in rates of hospital admissions and bed occupancy of rural Aboriginal infants for respiratory and gastrointestinal infections during the study period; changes in rates for other infections were less marked and less consistent. Despite recent improvements, Aboriginal infants are hospitalized much more frequently and for longer than other infants because of these diseases. Hospitalization rates reflect many factors including disease incidence and severity but also are affected by isolation, climatic and physical conditions, and access to medical and nursing care. Preventive health programmes need to be maintained and intensified in order to improve health standards of young Aborigines and to lessen their need for hospital care. PMID- 7865263 TI - Clothing and bedding and its relevance to sudden infant death syndrome: further results from the New Zealand Cot Death Study. AB - As part of a large nationwide case-control study covering a region with 78% of all births in New Zealand during 1987-90, the clothing and bedding of infants dying of sudden infant death syndrome (SIDS) and that of an appropriate control group were recorded. Cases consisted of 81% (n = 393) of all cases of SIDS in the study area and 88.4% (n = 1592) of 1800 control infants randomly selected from the hospital births and who completed a home interview. Use of a wool 'waterproof' underblanket was associated with a significantly reduced risk of SIDS (adjusted OR 0.44; 95% CI: 0.26-0.73) while sheepskin use was not. Firm tucking was identified as contributing to a reduced risk of SIDS even after adjusting for potentially confounding variables (adjusted OR 0.63, 95% CI: 0.46 0.86). Sixty case infants (15.6% of cases) were found dead with the head covered but there were no equivalent data for controls. Having been found previously completely covered by bedding was equally common in cases and controls (28.8% cases and 30.6% of control infants). Other differences of bedding and clothing between cases and controls were small; mattress characteristics were not studied. The exact methods in which babies are cared for are important and this study suggests that infants are at lower risk of SIDS when firmly tucked in and when sleeping on a 'waterproof' wool underblanket. PMID- 7865264 TI - Application of capture-recapture methodology to estimate the completeness of child injury surveillance. AB - This paper describes the use of the two sample capture-recapture method to estimate the completeness of ascertainment of injury events in both routine public hospital discharge statistics and in an active injury surveillance system. For all child pedestrian injuries public hospital discharge statistics were 90% complete and the active surveillance system 77% complete. For non-traffic child pedestrian injuries public hospital discharge statistics were 66% complete, the active surveillance system being 79% complete. Capture-recapture methods have the potential to improve the accuracy of traditional childhood injury surveillance systems. PMID- 7865265 TI - Analysis of paediatric tumour types associated with hemihyperplasia in childhood. AB - In order to further explore the relationship between hemihyperplasia in children and the occurrence of embryonal tumours of childhood, the records at St Jude Children's Research Hospital were examined for patients who presented with a malignant tumour and hemihyperplasia. Of 27 evaluable patients, 19 had Wilm's tumour and one had massive bilateral nephroblastomatosis. The tumours were more likely to occur on the side affected by hemihyperplasia than to be found contralaterally. All but five of these patients developed the tumours before the age of six. Twenty-two of the 27 patients developed tumours associated with allelic loss on chromosome band 11p15, suggesting that the locus associated with hemihyperplasia may be also located at chromosome band 11p15. PMID- 7865266 TI - Reduction of craniofacial and palatal narrowing in very low birthweight infants. AB - Many infants born preterm have positional moulding of the head and palate. This study investigates whether specially designed, foam pressure dispersing pads (PDP) worn throughout the neonatal hospital course, were not only effective in reducing craniofacial flattening, but also in lessening palatal narrowing in very low birthweight (VLBW) infants. The study was conducted in two phases. Twenty three consecutively born VLBW infants were randomly selected to act as a comparative group. The next 31 VLBW infants born comprised the intervention group, and wore PDP during hospitalization. The two groups were similar in birthweight and gestational age. The groups were compared for changes in craniofacial and palatal parameters at three time intervals during hospitalization. Results indicated a significant increase in growth of craniofacial width, palatal width and palatal area of infants wearing PDP compared to those infants not wearing them. These findings suggest that craniofacial and palatal narrowing observed in VLBW infants may be reduced by the wearing of PDP during hospitalization. PMID- 7865267 TI - Health beliefs among New Zealand adolescents. AB - A modified version of the Multidimensional Health Locus of Control (MHLC) scale was administered to 837 adolescents, aged 15 years, to assess their beliefs about health. There were significant sex differences on the total scores of the internal and powerful others dimensions of the scale. MHLC beliefs were not significantly associated with self-reported ratings of general health or mental health. Significantly more distress due to the experience of negative life events was reported by females with a strong internal locus of control. Maternal health beliefs showed stronger associations with daughters' health beliefs than sons'. For males, strong beliefs in an internal locus of control and weak beliefs in chance were significantly associated with aspects of attachment, social support and self-perceived strengths. There were weak correlations for the majority of associations between health beliefs and health measures and most of the adolescents reported either good or very good health. The findings suggest that adolescents' health beliefs may be quite different from those of adults. PMID- 7865268 TI - Sole parenthood and the risk of child pedestrian injury. AB - Children of sole parents have the worst mortality record of all social groups. Road vehicle related injuries account for a large part of their excess mortality. In this case-control study the association between sole parent status and the risk of child pedestrian injury was examined. Cases (n = 258) were children killed or hospitalized as a result of a pedestrian injury in the Auckland region over a period of 2 years and 2 months. Controls were a random sample of the child population. The children of sole parents were at a significantly increased risk of injury (odds ratio = 1.57; 95% confidence interval (CI) 1.09, 2.27). However, there was a striking difference in the effect of sole parent status according to ethnic group. Among European families, sole parenthood was associated with a greatly increased risk of injury (OR = 3.13; 95%CI 1.84, 5.31), whereas in Pacific Island families sole parenthood was associated with a significant protective effect (OR = 0.40; 95%CI 0.18, 0.89). The protective effect of sole parent status in Pacific Island families may reflect the beneficial effects of the social support provided by extended family networks. Children of sole parents in the context of the nuclear family may be particularly vulnerable. PMID- 7865269 TI - Incidence of apnoea and bradycardia in preterm infants following triple antigen immunization. AB - Ninety-seven preterm infants were immunized with diphtheria-tetanus-pertussis (DTP) prior to discharge from hospital. The mean gestational age at birth was 28.1 weeks (range 24-34) and the mean age at immunization was 80.6 days (range 44 257). Nineteen (20%) infants developed apnoea or bradycardia within 24 h of immunization. The infants who developed apnoea and/or bradycardia had a younger gestational age at birth than those who did not (P = 0.03), were artificially ventilated for longer (P = 0.01) and were more likely to have a diagnosis of chronic lung disease (P = 0.006). In the majority of infants these events were not clinically significant. Two infants who developed concurrent upper respiratory tract infections required additional oxygen and one of them was treated with oral theophylline. In general, it is safe practice to immunize preterm infants with DTP unless otherwise contraindicated. However, it is recommended that cardiorespiratory function is monitored after immunization in very preterm infants who had prolonged ventilatory support and/or chronic lung disease. PMID- 7865270 TI - Urinary N-acetyl-beta-D-glucosaminidase excretion in term and preterm neonates. AB - Urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion was measured in term and preterm neonates on days 1, 4, 7, 14 and 28 of life. Urinary NAG showed a peak level on day 4 or 7 in these infants. In addition, it tended to be higher with the degree of prematurity. In sick preterms who were depressed at birth and had respiratory failure, the NAG activity was further elevated during the first 2 weeks, suggesting the presence of renal tubular injury in this period. These observations thus suggest that urinary NAG may be a sensitive measure of renal maturation or damage in neonates. PMID- 7865271 TI - Plant sources of acid stable lipases: potential therapy for cystic fibrosis. AB - Exogenous lipase used in the treatment of pancreatic insufficiency may be destroyed by stomach acid. This study was undertaken to search for a readily available source of acid stable lipase. Eleven plant sources (avocado, walnut, pinenut, coconut, lupin, lentils, chickpea, mungbean, oats, castor beans and eggplant) were screened for lipolytic activity using a newly developed radio isotopic labelled substrate method. The results obtained by this method were confirmed by thin layer chromatography. Two of the sources (castor bean and dehulled oats) showed significant lipolytic activity at pH 5.6, castor beans containing 1.5 U/mg of extracted solid and oats 400-1200 U/mg of extracted solid. Castor beans are difficult to obtain and so may be an impractical commercial source of lipase; however, oats are abundant. If simple methods of enzyme purification and concentration can be developed, oats may prove to be a practical source of acid stable lipase for use in the treatment of patients with pancreatic insufficiency, especially those who have cystic fibrosis. PMID- 7865272 TI - Post-transfusion chronic hepatitis C in children. AB - Two hundred and twenty-six patients who received blood products for open-heart surgery in childhood were screened by a second-generation enzyme-linked immunosorbent assay and with surrogate markers for hepatitis C virus (HCV) infection, such as alanine aminotransferase (ALT). Twenty-two (14%) of the 161 recipients who received blood products before 1989 and none of the subjects who had received blood products after 1990 (the year that the blood bank began to screen for HCV antibody) were HCV seropositive. Virologic and histologic studies showed that 10 (45%) of 24 seropositive patients had persistent hepatitis C virus infection, many with ongoing hepatitis. The remaining 12 seropositive patients with absent HCV RNA had normal ALT levels, indicating resolved hepatitis C infection. Enrolment in screening is important to detect chronic hepatitis C in children who received blood products prior to screening of blood donors for HCV antibody. PMID- 7865273 TI - Genetic predisposition to hypertension (as detected by Na+/Li+ countertransport) and risk of diabetic nephropathy in childhood diabetes. AB - In order to evaluate whether insulin-dependent diabetes mellitus patients with incipient nephropathy have an overactivity of erythrocyte sodium-lithium countertransport (Na+/Li+ CT), 82 diabetic children and 38 healthy age-matched control subjects and their parents and grandparents were studied. The children were divided into two groups according to the presence of persistent microalbuminuria (MA). Diabetic children with MA had Na+/Li+ CT activity higher than normoalbuminuric diabetics and healthy controls. The parents and grandparents of microalbuminuric patients showed higher Na+/Li+ CT than parents and grandparents of normoalbuminuric diabetics and of the controls. This study demonstrates that predisposition to hypertension, as indicated by increased Na+/Li+ CT activity in erythrocytes, is more frequently detectable in patients with persistent microalbuminuria than in diabetics without persistent microalbuminuria or in healthy controls. Overactivity of Na+/Li+ CT is present also in parents and grandparents of diabetic children with MA. This study suggests that genetic predisposition to hypertension is more frequent in patients at risk of developing diabetic nephropathy, as well as in their parents and grandparents. PMID- 7865274 TI - Pulmonary thromboembolism and unexpected death in infancy. AB - Review of the Department of Histopathology autopsy files over a 30 year period from 1962 to 1991 revealed only three cases in which unexpected death occurred in infants under 1 year of age due to massive pulmonary thromboemboli. Predisposing factors included necrotizing enterocolitis with gut perforation and sepsis, a ventriculoatrial shunt and idiopathic arterial calcification. Diagnosis of the latter autosomal recessive condition was only made at autopsy. These cases demonstrate that pulmonary thromboembolism is a possible, although exceedingly rare, cause of sudden infant death, that some predisposing factors are unique to infancy and that the source of the pulmonary thromboembolus may be difficult to determine at autopsy. Massive pulmonary thromboembolism in infancy may point to the presence of other significant, clinically-unsuspected, disorders. PMID- 7865275 TI - Congenital Candida pneumonia in a preterm infant. AB - A 24 week gestation survivor of congenital Candida pneumonia who received prompt antifungal treatment and modern neonatal intensive care is reported. It was an unusual case in that fungal chorioamnionitis occurred without a foreign body in the maternal genital tract. Early diagnosis and treatment of congenital fungal pneumonia was possible because of prior knowledge of the obstetric history. Amphotericin B was successfully used for the treatment of this condition but combination with fluconazole (a fungistatic agent) was unsatisfactory and may be undesirable. Dexamethasone therapy to assist extubation was instituted once the fungal infection had been successfully controlled. PMID- 7865276 TI - A national policy on asthma management for schools. PMID- 7865277 TI - Severe thrombocytopenia in ELBW infants with systemic candidiasis. PMID- 7865278 TI - Laboratory confirmed sentinel surveillance of viral infections. PMID- 7865279 TI - Growth hormone treatment on chronic renal failure. PMID- 7865280 TI - Emerging epidemiologic patterns of HIV in the United States. PMID- 7865281 TI - Advances in AIDS Vaccine Development: 6th Annual Meeting of the National Cooperative Vaccine Development Groups for AIDS. Alexandria, Virginia, October 30 November 4, 1993. PMID- 7865282 TI - Immunogenicity and HIV-1 virus neutralization of MN recombinant glycoprotein 120/HIV-1 QS21 vaccine in baboons . AB - The effect of adjuvant and immunization schedule on the immunogenicity of HIV-1 envelope glycoprotein, MN rgp120, was optimized by using baboons. The novel adjuvant QS21 elicited earlier seroconversion than alum adjuvant, and the antibody titers to MN rgp120 for animals treated with QS21 were significantly greater than the titers obtained in animals treated with alum. The use of QS21 shifted the dose-response curve, resulting in less MN rgp120 required to achieve equivalent titers to those in the alum formulations. The in vitro virus neutralizing (VN) titers from animals treated with QS21 were 3- to 10-fold higher than with alum. The data presented herein point to the superiority of QS21 as adjuvant in primates for MN rgp120. PMID- 7865283 TI - Mechanisms behind the immune response induced by immunostimulating complexes. PMID- 7865284 TI - Mucosal immunity in the female genital tract: relevance to vaccination efforts against the human immunodeficiency virus. AB - The development of vaccines that induce specific immune responses in the genital tract secretions would have far-reaching implications for the prevention of AIDS and other sexually transmitted diseases. Most of the currently studied vaccines utilize systemic routes of immunization that are of limited value for the prevention of mucosa-contracted diseases. The relative contribution of antigen sensitized cells and IgA-committed lymphocytes from IgA inductive sites (e.g., Peyer's patches and rectal tonsils) to remote or adjacent effector sites (e.g., salivary glands and female genital tract) as manifested by the appearance of corresponding secretory antibodies has not been studied in humans despite its unquestionable practical importance. Exploitation of immunization routes that are effective for induction of mucosal immune responses and reflect our current knowledge of the origin of antibodies and of specific antibody-forming cells in mucosal tissues is likely to reduce the incidence of many infectious diseases including AIDS. PMID- 7865286 TI - Effect of mutations in rev gene of SIVmac on virus replication. AB - The functional activity of SIVmac251 Rev was altered by introducing amino acid changes inside and chain termination mutations after the Rev response element binding region (RBR) of the protein. The effects of specific mutations were evaluated by transfecting proviral DNAs into the HeLa cell line and into HeLa cells constitutively expressing either HIV-1 Rev or HTLV-1 Rex proteins. Cell free supernatants from these transient expression assays were further characterized by infecting CD4-positive lymphoid cell lines H9 and MT-4, the latter abortively infected with HTLV-1, and human peripheral blood mononuclear cells. These results together with the data from cotransfection experiments show that SIV can be attenuated up to 95% by introducing changes into the arginine rich domain, RBR, of Rev. These recessive mutations were efficiently complemented in trans by HIV-1 Rev, SIV Rev, and HTLV-I Rex proteins. In contrast, the mutants of Rev protein that had a chain termination after RBR were trans-dominant negative and could not be trans-complemented with any of these three regulatory proteins. When additional mutations were inserted into the RBR of these trans dominantly negative Rev proteins, complementation was obtained again. PMID- 7865285 TI - Vaccine protection and reduced virus load from heterologous macaque-propagated SIV challenge. AB - The efficacy of vaccine protection afforded by live attenuated vaccines was tested by heterologous SIVtno8980 challenge following successful protection against homologous SIVmac32H challenge. Animals immunized with the attenuated SIVmacBK28 molecular clone were asymptomatic and virus isolation negative by quantitative virus isolation prior to challenge. Two groups of four animals previously immunized 5 years and 4 months (respectively) were challenged with 100 MID50 of SIVtno8980, as was a third group of four naive controls. All control animals that were challenged developed high levels of plasma antigenemia within 2 weeks of challenge and developed rapid Th/m cell loss whereas vaccinated animals did not. Quantitative virus isolation from peripheral blood mononuclear cells revealed that one of four animals in each group became virus isolation positive but that the virus load in the two vaccinated animals was markedly lower than in nonvaccinated controls. Studies are underway to determine the duration and immunological correlates of protection from AIDS. PMID- 7865287 TI - HIV-1 infection in pigtailed macaques. AB - Four pigtailed macaques were inoculated with autologous cells expressing low levels of human immunodeficiency virus type 1 (HIV-1). During the first 10 weeks, infectious virus was recovered from peripheral blood mononuclear cells (PBMCs) and lymph nodes from three of the animals. Subsequently, HIV-1 DNA was frequently detected in uncultured PBMCs from all three animals, and virus was isolated from one of them at weeks 38 and 61. The fourth animal, which was rechallenged at week 10 with cell-free virus isolated from one of the others, never became virus isolation positive, but harbored HIV-1 proviral genomes. These virus infections were accompanied by the development of varied HIV-1-specific humoral immune responses. Antibodies to gp160 were first apparent at week 8 in the three initially infected animals and persisted. The animal from whom virus was isolated at late times also developed persisting antibodies to HIV-1 p24 and gp120. Antibodies to gp120 and gp160 became apparent in the rechallenged animal at 1 week following reinoculation, but they waned with time. In vivo passage of the virus was attempted at week 6. One recipient pigtailed macaque and one recipient cynomolgus monkey failed to become detectably infected following transfusion of virus-positive blood and lymph node cells. The long-term presence of HIV-1 specific antibodies and proviral genomes in these animals, and the recovery of infectious virus more than 1 year following inoculation, are indicative of persistent infection, and confirm previous reports that pigtailed macaques are susceptible to HIV-1. PMID- 7865288 TI - Safety profile of HIV vaccination: first 1000 volunteers of AIDS vaccine evaluation group. NIAID AIDS Vaccine Clinical Trials Network. PMID- 7865289 TI - Phase I/II trials of preventive HIV vaccine candidates. Dose and schedule: summary. PMID- 7865290 TI - Serological responses to candidate AIDS vaccines. PMID- 7865291 TI - Preliminary results of V3 loop peptide-primary neutralizing domain conjugate phase 1 vaccine trail. PMID- 7865292 TI - Conference on advances in AIDS vaccine development--1993. Report of Perinatal Intervention Working Group. PMID- 7865293 TI - Conference on advances in AIDS vaccine development--1993. Summary: Mucosal Immunity Workshop. PMID- 7865295 TI - Conference on advances in AIDS vaccine development--1993. Summary: cytotoxic T cell Immunity Workshop. PMID- 7865294 TI - Conference on advances in AIDS vaccine development--1993. Summary: correlates of HIV Immunity Working Group. PMID- 7865296 TI - Towards a preventive HIV vaccine--lessons from history. PMID- 7865297 TI - Preparations for AIDS vaccine trials. Respecting concerns of international host countries. PMID- 7865298 TI - Preparations for HIV vaccine trials: moving from baseline studies to efficacy trials. AB - In summary, much has been accomplished in the past year, but much still remains to be done before we can embark on an efficacy trial. With the availability of a fully operational network, the NIAID has in place the resources and mechanisms to complete baseline feasibility studies and to conduct the future trials. As presented at the 1993 conference and reported in this supplement, the preliminary data from the current baseline studies indicate that such trials are feasible, although not without considerable problems. To reach our "efficacy trials preparedness" goal, we will need to work especially hard in the coming months to identify and resolve the remaining technical, ethical, legal, and political constraints to initiating trials. We must also listen to community concerns and educate the public about the trials if we expect to gain community support and volunteers for the study. Finally, we must evaluate the supporting data pertaining to candidate products for efficacy trials. These will not be easy tasks or decisions, but we must approach them with vigor. PMID- 7865299 TI - Overview: HIV vaccine feasibility studies. PMID- 7865300 TI - Preparations for AIDS vaccine trials. Recruitment and retention of in- and out-of treatment injection drug users. PMID- 7865301 TI - Preparations for AIDS vaccine trials. Incident human immunodeficiency virus (HIV) infections in a cohort of injection drug users in Baltimore, Maryland. AB - In order to prepare for a possible trial of a preventive human immunodeficiency virus (HIV) vaccine in a population of injection drug users (IDUs) we followed a cohort to determine their HIV incidence, compliance with follow-up visits at 3 month intervals (i.e., quarterly) and their attitudes toward HIV vaccine trial participation. A population of 671 HIV-seronegative subjects were recruited from a cohort of IDUs already in follow-up in Baltimore, MD (the ALIVE study). We detected 19 seroconverters in 1677.80 person-quarters of follow-up, an annual incidence of 4.52/100 person-years. Compliance with quarterly follow-up was 93% at 6 months and 89% at 9 months. Although many subjects (n = 104) are not yet due for their 12-month visit, compliance to date has been 76%. The most sensitive risk behaviors associated with HIV seroconversion have been continued injection of illicit drugs and the frequency of drug use. Other reported drug associated risk behaviors, e.g., needle sharing and shooting gallery use, have decreased despite a high HIV incidence; we believe some of the reported reductions in high risk behavior represent socially desirable responses by the study subjects. Although the difficulties in successfully doing a trial of an HIV vaccine in the population should not be underestimated, our data suggest that such a trial would be feasible. PMID- 7865302 TI - Preparations for AIDS vaccine trials. Retention, behavior change, and HIV seroconversion among injecting drug users (IDUs) and sexual partners of IDUs. AB - The likelihood that subjects in human immunodeficiency virus (HIV) vaccine efficacy trials will alter their behavioral risks for HIV infection over time must be considered in evaluating the feasibility of such trials and in estimating the necessary sample sizes to be enrolled. Potential subjects for future vaccine efficacy trials include injecting drug users (IDUs) and others who may be difficult to retain in studies and who may alter HIV-risk-related behaviors substantially over time. We have investigated behavior change, retention, and HIV seroconversion among 577 New York City resident IDUs and sexual partners of IDUs enlisted between July 1 and December 31, 1992. We attempted to see all subjects every 3 months for interviews, blood donation and HIV testing. We were able to retain 68% of subjects in the study through the third scheduled recall at 7.5 10.5 months after enlistment. HIV seroconversion through March 1, 1994, was 1.33/100 person-years at risk. There was a significant inverse relationship between HIV seroconversion and retention at the 9-month recall after adjusting for age, gender, and the amount of locator information provided by subjects at enlistment. Among subjects seen at each of the scheduled visits at 3, 6, and 9 months after enrollment, modest but statistically significant behavior changes that reduced risk were observed in self-reported drug injection frequency, heroin injection frequency, sexual contact with IDUs, and sharing of needles/syringes. The magnitude of these changes in risk, however, was small and may be transient. The behavior changes observed to date do not appear to be large enough to substantially alter calculations of sample sizes needed in future HIV vaccine efficacy trials. PMID- 7865303 TI - Development of a single-shot subunit vaccine for HIV-1. AB - The successful development of an AIDS vaccine will require formulations that not only invoke the desired immunological response, but also are stable and easy to administer. A single shot MN rgp120 vaccine formulation comprised of MN rgp120 encapsulated in poly (lactic-coglycolic) acid (PLGA) microspheres was developed to provide an in vivo autoboost of antigen. These formulations were designed to yield an in vivo autoboost at 1, 2, 3 or 4-6 months. In addition, PLGA microspheres containing the adjuvant, QS21, were also prepared to provide an in vivo autoboost concomitant with antigen. In guinea pigs, these formulations yielded higher anti-MN rgp120 and anti-V3 loop antibody titers than alum formulations that were administered at higher antigen doses. Different doses of encapsulated MN rgp120 provided a clear and well-defined dose response curve for both anti-MN rgp120 and anti-V3 loop antibody titers. When soluble QS21 was mixed with the encapsulated MN rgp120, the antibody titers were increased by a factor of 5 over the titers with encapsulated MN rgp120 alone. An additional fivefold increase in antibody titers was observed for guinea pigs immunized with encapsulated MN rgp120 and QS21 on the same microspheres. These results suggest that the adjuvant properties of QS21 can be increased by microencapsulation in PLGA. Furthermore, antibodies induced by these preparations neutralized the MN strain of HIV-1. The neutralization titers for sera from animals immunized with MN rgp120-PLGA and soluble QS21 were greater than the titers obtained from guinea pigs that were treated with MN rgp120 and soluble QS21 at the same dose. Overall, these studies validate the in vivo autoboost concept, reveal a method for improving the adjuvant properties of QS21, and indicate the potential of future single shot vaccine formulations. PMID- 7865305 TI - Preparations for AIDS vaccine trials. Discussion on progress in domestic cohort development and evaluation. PMID- 7865304 TI - Seroprevalence and seroincidence of HIV-1 in injection drug users using the VA system. PMID- 7865306 TI - Preparations for AIDS vaccine evaluations. Progress in international cohort development and evaluation. PMID- 7865307 TI - Preparations for AIDS vaccine evaluations. AIDS International Training and Research Program. PMID- 7865308 TI - Feasibility and cohort development for HIV vaccine trials in Haiti. AB - Human immunodeficiency virus (HIV) infection is spreading rapidly in Haiti with HIV seroprevalence rates of 10% and 3% in urban and rural areas, respectively. Since 1985, heterosexual transmission has been the primary mode of acquisition of HIV. From 1981 to the present, the Cornell-GHESKIO unit in Port-au-Prince, Haiti, has developed the infrastructure to recruit and retain large cohorts of individuals at risk for HIV infection. Among the populations studied, couples discordant for HIV infection appear most suitable for eventual HIV phase III vaccine trial. This paper describes the recruitment, retention, and characteristics of the discordant-couples cohort, as well as the limitations of interventions aimed at behavior modification. PMID- 7865309 TI - Preparation for AIDS vaccine evaluation in Mombasa, Kenya: establishment of seronegative cohorts of commercial sex workers and trucking company employees. AB - In preparation for human immunodeficiency virus (HIV) prophylactic vaccine trials, prospective cohorts of HIV seronegative female commercial sex workers and male trucking company employees were established in Mombasa, Kenya, with the aims of defining HIV seroincidence and correlates of HIV seroconversion. Female and male cohorts were followed at 1- and 3-month intervals, respectively, with questionnaires, physical examinations, evaluation for sexually transmitted diseases, and HIV serologic testing. Between February and September, 1993, 1,277 women and 748 men were tested for antibodies to HIV-1. Seroprevalence was 55.4% among commercial sex workers and 17.7% among trucking company employees. Three hundred fifty-two HIV-seronegative women and 507 seronegative men were enrolled in the cohort studies. Annualized seroincidence rates of HIV infection were 16.4% (95% CI 8.8-27.0) among commercial sex workers and 6.6% (95% CI 2.5-13.8) among trucking company employees. These cohorts may be valuable resource for evaluating HIV vaccines and other potential preventive interventions. PMID- 7865310 TI - Preparations for AIDS vaccine evaluations. Rate of new HIV infection in a cohort of women of childbearing age in Malawi. PMID- 7865312 TI - HIV preventive vaccine efficacy trials in the United States: an overview of target communities' concerns. PMID- 7865311 TI - Preparatory studies for possible HIV vaccine trials in northern Thailand. AB - We studied several populations of human immunodeficiency virus (HIV)-seronegative individuals from northern Thailand who were believed to be at relatively high risk of HIV infection in order to assess their potential suitability for inclusion in a preventive HIV vaccine trial. Included were female commercial sex workers (CSWs), male sexually transmitted disease (STD) clinic patients, male conscripts into the Royal Thai Army (RTA), and men who were recently discharged from the army. We evaluated their HIV prevalence, their interest in study participation, their compliance with prospective follow-up, and their HIV incidence. Among 1068 female CSWs the baseline HIV prevalence was 38.3%; of 659 HIV seronegatives 395 (59.9%) agreed to enrollment in the study. Follow-up at 6-9 months was 73.2%; it was 58% in brothel-based CSWs and 85% in non-brothel-based CSWs. Overall HIV incidence in CSWs was 8.2 per 100 person-years; incidence was 29 per 100 person-years in brothel-based CSWs and 4 per 100 person-years in non brothel-based CSWs. Among 1031 male STD clinic patients, baseline HIV prevalence was 15.9%, follow-up was successful in 98.1%, and HIV incidence was 4.0 per 100 person-years. Among four cohorts of RTA conscripts who entered the military in 1991 and 1993, baseline HIV prevalence has been about 12%, follow-up about 90%, and HIV incidence has varied from 1.2-3.2 per 100 person-years. Discharged RTA conscripts have had baseline HIV prevalence of about 13%, successful follow-up of 94%, and an HIV incidence of about 5 per 100 person-years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865313 TI - Participation of homosexual/bisexual men in preventive HIV vaccine trials: baseline attitudes and concerns and predicted behaviors during trials. PMID- 7865314 TI - The decision to enroll in HIV vaccine efficacy trials: concerns elicited from gay men at increased risk for HIV infection. PMID- 7865315 TI - Interest in HIV vaccines among injection drug users in Baltimore, Maryland. AB - To gauge interest about participation in human immunodeficiency virus type 1 (HIV vaccines, we interviewed 375 HIV-seronegative injecting drug users who are participants in an ongoing longitudinal study of HIV infection. Nearly all (93%) responded that they thought it likely that an HIV vaccine would become available, and 85% expressed interest in participating in a study of vaccine effectiveness. However, levels of interest decreased to 47% when respondents were informed that the vaccine might result in a positive HIV test and to 27% when offered to be in a study where the vaccine might contain a piece of the virus. Factors that increased interest in trial participation included assurances of confidentiality, being fully informed about the protocol and remuneration. Most respondents (78%) felt that injecting drug users would maintain other risk reduction activities (e.g., condom use) if they participated in a vaccine study. These data suggest a high level of interest for participation in HIV vaccine trials, but that more education about vaccines and the risks involved is needed. Ongoing communication with the community and responsiveness to community concerns is crucial to achieve a successful vaccine study. PMID- 7865316 TI - Immunization with virion-derived glycoprotein 130 from HIV-2 or SIV protects macaques against challenge virus grown in human or simian cells or prepared ex vivo. AB - We have compared in the macaque model the efficacy of the virion-derived glycoprotein of HIV-2ben (HIV-2 gp130) with that of SIVmac251/32H (SIV gp130). The latter vaccination trial was in part combined with vaccinia virus (VV) priming. Both antigen preparations induced a strong humoral, but a weak cellular, immune response. The first challenge was performed with autologous virus grown on a human T cell line. More than 50% of the monkeys immunized with HIV-2 gp130 (five of nine) and 63% of the monkeys immunized with SIV gp130 (five of eight) were protected. All such protected animals received one or two booster immunizations before they were rechallenged either with heterologous HIV-2SBL6669 grown on monkey peripheral blood mononuclear cells or with an ex vivo stock of SIVmac251/32H prepared from the spleen of an SIV-infected macaque and not passaged in vitro. Immunization with HIV-2 gp130 did not protect against the second challenge, but one animal showed limited infection as indicated by positive PCR only. Challenge of the SIV gp130-immunized monkeys with the spleen derived virus led to infection of three animals; remarkably, one of these was only PCR positive. Two animals were completely protected. Thereby we can exclude the influence of cellular proteins on protective immunity. Priming with VV was not superior to immunization with gp130 alone. Neither at the first nor at the second challenge were the virus-specific humoral and cellular immune responses of the vaccinees clearly correlated with protection. However, neutralizing antibodies may have been important in the SIV gp130-immunized animals at first challenge. PMID- 7865317 TI - Behavioral studies relevant to vaccine trial preparation: an introduction. AB - Preparations for large-scale trials to test the efficacy of candidate HIV vaccines can benefit in several crucial ways from a targeted program of behavioral and social research. Randomized field experiments testing alternative procedures for the recruitment and retention of subjects can help identify research procedures that will ensure adequate sample sizes while minimizing sample attrition over time. Similarly, assuring that subjects accurately comprehend the potential risks of participation will require more than simply presenting scientifically accurate information. Ensuring both the adequacy and appropriateness of risk communications as well as the accuracy of subject perception of risks (across the social and cultural milieux in which vaccine trials will be undertaken) is a critical task. Ethnographic and behavioral studies can help to ensure that our obligation to obtain truly informed consent from our research subjects is fully met and documented. Monitoring risk behaviors over the course of the vaccine trials could also benefit from strategic investments in new technologies developed by social researchers to permit the collection of sensitive personal data while affording complete privacy to subjects. These new measurement technologies include procedures that permit private data collection (without a human interviewer) in any spoken language and without requiring that subjects be literate. PMID- 7865318 TI - Behavioral research contributions to planning and conducting HIV vaccine efficacy studies. PMID- 7865319 TI - Preparations for AIDS vaccine trials. An automated version of the Risk Assessment Battery (RAB): enhancing the assessment of risk behaviors. AB - Our primary objective during this pilot work has been to determine if the computerized RAB can be used in place of the paper-and-pencil version with an IDU population. As stated, reliability estimates in the form of correlations of risk scores between the two versions ranged from .82 to .94, and percentages of exact agreement of the scoreable items ranged from 88% to 100%. These correlations indicate that the C-RAB is comparable to the RAB in its psychometric properties. Further, subjects' positive ratings of the computer program and perceptions that it would better protect confidentiality indicate that this population would participate in assessments involving computer interactions. While these self reports may be biased on clients' desire to be cooperative and the novelty of the assessment approach, the high level of approval ratings suggest that a majority of participants do prefer completing assessments on the computer. Similarly, participants' demonstrated ability to use the computer and their rating of the program as easy to use suggest that the C-RAB has potential to be a reliable and efficient tool in assessing risk behaviors among IDUs enrolled in HIV vaccine trials. PMID- 7865320 TI - Preparations for AIDS vaccine trials. Developing brief valid screening instruments for HIV-related sexual risk behavior among gay and bisexual men. AB - Enrolling and tracking cohorts for HIV vaccine efficacy trials requires that participants disclose behaviors that place them at risk for exposure to HIV. Brief screening procedures have been suggested for this purpose. In a previous study gay and bisexual men in three U.S. cities reported unprotected anal intercourse on a brief screening instrument. Screen reports were compared to subsequent in-depth, face-to-face interview data; 29% of the men who reported unprotected anal intercourse during the interview failed to disclose this behavior during screening. For recruitment into an HIV vaccine feasibility study at the same study sites, screening procedures were modified to encourage accurate reporting: to lessen stigma, low risk as well as high risk sexual behaviors were assessed, and screens were administered by trained study staff who presented it as a tool for understanding the gay community. Failures to disclose risk decreased to 18%, a rate that, while lower than in the previous study, remains high. Men less likely to disclose unprotected sex during the screen engaged in fewer high risk sexual behaviors, had more stringent norms regarding sexual safety, and were less identified with the gay community than were men who disclosed unprotected sex. Failure to disclose risk may have significant implications for participant selection and behavior tracking during vaccine trials. More systematic assessments that are sensitive to target communities may facilitate disclosure. PMID- 7865321 TI - Global HIV vaccines: economic considerations. PMID- 7865322 TI - Preparations for HIV vaccine efficacy trials. Vaccine selection guidelines. National Institute of Allergy and Infectious Diseases, National Institutes of Health. PMID- 7865323 TI - Vaccine liability and participant compensation incentives in HIV vaccine trials. PMID- 7865324 TI - HIV vaccines for injection drug users in the context of a comprehensive prevention agenda. AB - Human immunodeficiency virus (HIV) infection among injecting drug users remains a major health problem. Traditional approaches to prevent parenteral transmission of HIV infection in this population include abstinence facilitated through treatment for drug abuse, HIV testing with education and counseling, disinfection of needles with bleach between uses, and needle exchange programs. While each of these strategies are important and contribute to risk reduction, high-risk behavior and transmission of HIV infection continues. The development and distribution of safe and effective HIV vaccines in this population is urgently needed. PMID- 7865325 TI - Preparations for AIDS vaccine trials. Intellectual property issues related to AIDS vaccine development from a federal laboratory perspective. PMID- 7865326 TI - The role of prevention research in HIV vaccine trials. AB - The National Institute of Allergy and Infectious Diseases has prepared for HIV vaccine efficacy trials with the hope of having a product which is deemed worthy of testing. This has entailed development of new field research infrastructure and training, in collaboration with many partners. Notably, experts in observational research and experts in field HIV prevention research have joined together in efforts to share their mutually reinforcing experiences. In crafting these potential trial sites, it has become evident that the same criteria that apply in vaccine site suitability should also apply to other prevention clinical trials. These criteria include novel approaches to barriers to sexual transmission, including topical microbicides/spermicides, treatment of sexually transmitted infections, reduction in intrapartum blood contamination, and various strategies to ensure clean needle use. Like vaccines, most of these interventions are theoretically plausible, but remain untested. With or without large scale vaccine trials, these other prevention technologies remain high priorities for HIV research. PMID- 7865327 TI - Panel discussion on vaccine development to meet U.S. and international needs. Perspectives on national and global HIV vaccine development: potential ways to reduce impediments for biopharmaceutical product development. PMID- 7865328 TI - Panel discussion on vaccine development to meet U.S. and international needs. When manufacturers are unwilling to accept the risks or invest the capital: vaccine production by the Salk Institute to specifications of the U.S. Army. PMID- 7865329 TI - Panel discussion on vaccine development to meet U.S. and international needs. Strategies for reducing the disincentives to HIV vaccine development: description of a successful public-private sector international collaboration. PMID- 7865330 TI - Recent advances in AIDS vaccine research and development. AB - There is an urgent need for a prophylactic vaccine to protect individuals from AIDS and to help abate the growing epidemic. In October 1993, the Conference on Advances in AIDS Vaccine Development reviewed the state-of-the-art in vaccine research and confirmed both the progress that has been made and the challenges that remain. Approximately 12 candidate vaccines are now in phase I/II clinical trials. To date, these products appear to be safe and capable of eliciting immune responses in vaccinees. Other vaccine strategies in development include the use of new formulations and the design of vaccine products capable of inducing a mucosal immune response. Progress has also been made in the establishment of domestic and international sites at which efficacy trials can be conducted when appropriate vaccine candidates are identified, and preparatory activities at these sites are ongoing. The possibility that one or more candidates may enter efficacy trials within the next 2 years underscores numerous issues that must be considered in preparation for these trials. These include the importance of ease of vaccine administration and cost, and an array of social, legal, and ethical issues of concern to those individuals who will be asked to participate in efficacy trials. The purpose of this article is to highlight recent advances in vaccine research and development and to define the complex factors that will impact the NIAID's position on advancing candidates into phase III trials. PMID- 7865331 TI - DNA inoculation induces protective in vivo immune responses against cellular challenge with HIV-1 antigen-expressing cells. AB - Direct DNA inoculation induces immune responses through the delivery of nonreplicating transcription units that drive the synthesis of specific foreign proteins within the inoculated host. These proteins are processed within host cells and through association with relevant MHC antigens that can become the subject of immune surveillance and elicit immune responses against pathogens. Direct introduction of DNA into mice has been reported to be antigenic as demonstrated by the use of this technique to develop immune responses against human growth hormone, influenza proteins, as well as HIV-1 proteins. Most recently the demonstration of the use of this technology to produce anti-HIV-1 immune responses has been reported in nonhuman primates. Accordingly a more detailed analysis of this technology could generate important insight into the generality of this approach for immune therapy or vaccine design. In this article we further our investigation of direct DNA inoculation as a tool for induction of relevant immune responses against HIV-1 in vivo. We demonstrate expression of HIV 1 antigens in the inoculated muscle of animals. Inoculated animals demonstrate significant cytotoxic T cell responses against HIV-1 antigen-expressing targets. Furthermore, using a novel challenge system, we demonstrate that the majority of immunized animals can reject lethal, HIV-1 antigen-expressing cell challenge in an antigen-specific manner. This technology has relevance for the development of immunization strategies against HIV as it provides for specific antigen production in vivo without the use of infectious agents. PMID- 7865332 TI - Accell particle-mediated DNA immunization elicits humoral, cytotoxic, and protective immune responses. AB - Accell particle-mediated gene delivery technology was employed for the intracellular delivery of antigen-encoding expression vectors in epidermal tissues in laboratory animals. Delivery of plasmid DNA-coated gold microparticles using the Accell gene delivery system resulted in de novo antigen expression in epidermal cells that stimulated the induction of antigen-specific humoral and cytotoxic cellular immune responses. Optimal DNA delivery conditions favoring maximal humoral responses required the delivery of 5 x 10(7) micron-sized gold particles containing 300 plasmid copies per particle (80 ng of vector total) into a 4-cm2 area of abdominal skin. Comparison of immune responses between animals that received intramuscular injections of relatively large quantities of vector DNA (100 micrograms) and those that received intracellular deliveries of submicrogram quantities of the same DNA to the epidermis demonstrated that the latter approach was considerably more effective at eliciting strong humoral responses. In addition, cytotoxic cellular immune responses were elicited to HIV 1 gp120 following epidermal delivery of HIV-1 gp160 or gp120 expression constructs. A qualitative shift from predominantly cytotoxic cellular to predominantly humoral immune responses with continued immunization indicated the potential for optimizing delivery conditions to favor specifically one type of response over the other. PMID- 7865333 TI - Libraries of human rhinovirus-based HIV vaccines generated using random systematic mutagenesis. AB - Human rhinovirus (HRV), an immunogenic and relatively nonpathogenic virus, has been engineered to display HIV-1 immunogens with the intent of developing a vaccine against AIDS. HIV immunogens from the V3 loop have been placed into the neutralizing immunogenic (NIm) sites on the surface of HRV14 naturally recognized by the immune system. To increase the likelihood of recovering viable chimeras displaying the transplanted HIV-1 V3 loop sequences in conformations that mimic that of HIV, we have used random systematic mutagenesis to produce libraries of chimeric HRV14 in which the transplanted epitope from HIV-1 is flanked by one or more randomized amino acid residues. This allows the HIV epitope to be accommodated into the HRV coat proteins in many conformations, some of which should result in the production of viable, immunogenic hybrids. Using this approach, a library containing the sequence XXIGPGRAXX, where X could be any of the 20 amino acids, was generated. A nonrandom distribution of residues was found at the randomized positions, which may be a reflection of the structural requirements for viability. A subset of chimeras was identified that reacted with neutralizing anti-HIV-1 V3 loop antibody preparations, indicating that the antigenicity of the epitopes had been transplanted. Another chimeric virus library was designed to reflect the natural diversity of the V3 loop by incorporating amino acids at frequencies similar to those found among naturally occurring isolates of HIV-1. Powerful selection techniques utilizing anti-HIV-1 V3 loop neutralizing antibodies are being employed to isolate efficiently antigenic chimeras that could serve as potential vaccine candidates. PMID- 7865334 TI - Dicistronic polioviruses as expression vectors for foreign genes. AB - We have made use of certain novel genetic elements of picornaviruses termed internal ribosomal entry sites (IRES) to construct a viral RNA with the following genetic order: PV 5' NTR-EMCV IRES-PV ORF-3' NTR (PV, poliovirus; NTR, nontranslated region; EMCV, encephalomyocarditis virus; ORF, open reading frame). Transfection of this RNA into HeLa cells yielded a poliovirus (W1-PNENPO) that contained two heterologous IRES elements (type 1 IRES of PV; type 2 IRES of EMCV) in tandem. The insertion of foreign coding sequences into the genome of W1-PNENPO between the IRES elements yielded viable polioviruses with the gene order PV 5' NTR-foreign ORF-EMCV IRES-PV ORF-3' NTR. The foreign ORFs we have employed in this study included the coding region for chloramphenicol acetyltransferase (CAT), or segments of either luciferase or the HIV-1 envelope glycoprotein gp120. W1-PV/V3-3, a dicistronic poliovirus that contained HIV-1-specific sequences that included the V3 domain of gp120, was used to infect transgenic mice (PVR+) that were engineered to express the poliovirus receptor. The genetic stability of the dicistronic viruses and the HIV-1-specific immune response in PVR+ mice after infection with these novel agents are discussed. PMID- 7865335 TI - New approaches for mucosal vaccines for AIDS: encapsidation and serial passages of poliovirus replicons that express HIV-1 proteins on infection. AB - It is apparent that a safe and effective HIV vaccine is an important component in the development of rational approaches for the control and prevention of HIV transmission. Given the fact that the virus most often encounters a mucosal surface during sexual transmission, a vaccine designed to stimulate both the systemic and mucosal immune systems is essential. Poliovirus is attractive as a delivery system because of several biological features inherent to the virus. First, the pathogenesis of the virus has been well studied, and important features have been identified. The virus is naturally transmitted by a fecal-oral route and is stable in the harsh conditions of the gastrointestinal tract. Second, previous studies using attenuated vaccine strains of poliovirus showed that a long-lasting systemic and mucosal immunity is generated after administration of the vaccines. Studies have demonstrated the presence of circulating T cells that proliferate to whole inactive poliovirus or peptides corresponding to amino acids of the VP1 proteins in previously immunized individuals. These results established that immunization with poliovirus stimulates both the humoral and cell-mediated components of the immune system. Third, the attenuated strains of poliovirus are safe for humans and are given to infants as early as 6 months of age. The incorporation of foreign genes into the attenuated strains would be an attractive feature that should pose no more of a health risk than that associated with administration of the attenuated vaccines. Finally, studies from this laboratory, as well as others, have established the feasibility of incorporating foreign genes into the poliovirus cDNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865336 TI - Evaluation of cytotoxic T cell responses to candidate HIV-1 vaccines in HIV-1 uninfected individuals. AB - The ability to induce a strong, HIV-1-specific CD8+ CTL response is assumed to be an important component of a protective HIV-1 vaccine. Identification of CTL responses in seronegative vaccines requires in vitro stimulation of CTL precursors with cells that have processed HIV-1 gene products via the endogenous intracellular pathway for presentation in association with MHC class I molecules. We have developed a method to detect CTL responses to HIV epitopes and HIV infected cells that can be applied to recipients of HIV vaccines regardless of immunization with a particular recombinant virus or prior immunological status. Primed CTL precursors from PBMCs are stimulated for two 1-week cycles with autologous monocyte-derived macrophages infected with HIV-1Ba-L. The effector CTLs generated in culture are then tested in a standard chromium release assay for lysis, using autologous target cells, including EBV-transformed lymphoblastoid cell lines (LCLs) expressing individual HIV-1 proteins following infection with a recombinant vaccinia virus, or LCLs transduced with the CD4 gene and infected with isolates of HIV. Using this methodology we have examined CTL responses induced by candidate HIV vaccines in HIV-1-uninfected individuals participating in phase I/II AVEG trials. Our findings indicate that this approach makes it possible to overcome some of the previous technical difficulties involved in the analysis of CTL responses in immunocompetent vaccine recipients and thereby facilitates the identification of potentially effective candidate HIV 1 vaccines. PMID- 7865337 TI - HIV vaccines in the context of a broader prevention agenda--views from urban U.S. projects: Washington, D.C. studies among adolescents. PMID- 7865338 TI - HIV-1 env-specific cellular cytotoxicity in HIV-1-seropositive mothers and their infants. PMID- 7865339 TI - Cytotoxic T lymphocyte activity in children infected with HIV. AB - Of the Edinburgh cohort of approximately 130 children born to HIV-infected women, 9 are infected and alive. This article describes results from the first 18 months of a natural history study of seven of these, and two adopted children, studying the CD8 T cell-mediated cytotoxicity against HIV proteins (Gag, Tat, Pol, and Env), over time, and relating it to clinical progression and viral activity. Autologous EBV cell lines infected with vaccinia-HIV constructs were used as target cells, and bulk-cultured peripheral blood mononuclear cells as effector cells. The children ranged in age from 0 to 93 months, with six of the nine showing CTL activity to one or more HIV proteins. The specificity of the response was directed against Tat in the younger children, switching to Pol, then Gag or Env. Preliminary analysis of virological data showed no association between CTL and virus activity. The children with CTLs tended to be well clinically, but the cohort needs to be studied longer before conclusions can be made about CTL activity and HIV disease progression. Cytotoxic T lymphocyte activity has also been observed in two children diagnosed as HIV uninfected. These results show the importance of looking at CTL specificity, and may have implications in vaccine design. PMID- 7865340 TI - Suitability of Trinidad/Tobago as a potential site for phase III efficacy studies of HIV-1 vaccines. PMID- 7865341 TI - Mechanisms of action of nonionic block copolymer adjuvants. AB - Nonionic block copolymer adjuvants typically induce high-titer, long-lasting antibody responses, cell-mediated immunity, CTLs, and modulate the isotype and specificity of antibody. Their primary activity is modulation of hydrophobic adhesive interactions. The copolymers adhere to lipids, promote retention of protein antigen to surfaces, activate complement, and induce expression of class II (IA) on macrophages. They produce a concentrated surface matrix of antigen and activated host mediators that facilitates antigen presentation to cells of the immune system. The copolymer adjuvants act synergistically with multiple MDP and LPS preparations to increase total titers, especially those of the IgG2a and IgG2b isotypes. A surprising discovery was that they influence the specificity of antibody by at least two mechanisms. Saline formulations and oil-in-water (o/w) emulsions induced more antibody against labile, conformationally dependent epitopes on the surface of particles than water-in-oil (w/o) emulsions. Finally, we found that very large copolymers are able to stabilize water-in-oil-in-water (w/o/w) or multiple emulsions that can protect antigen during passage through the upper GI tract. They are therefore attractive vehicles for oral delivery of vaccines. PMID- 7865342 TI - Lipid matrix-based subunit vaccines: a structure-function approach to oral and parenteral immunization. AB - Immunization is today the most effective defense mechanism against microbial infections. Although highly effective vaccines are currently available for a number of infectious diseases, vaccine formulations can still be improved in a number of important areas. The ability to induce antigen-specific humoral and cell-mediated immunity is crucial to the development of effective prophylactic and therapeutic vaccines for HIV and other pathogens. The approach of our laboratory has been to design and test simple, highly defined antigen-lipid complexes that would stimulate antibody and cell-mediated immune responses in the absence of any nonspecific immunological activators such as Freund's adjuvant, lipopolysaccharide (LPS), or alum. These studies have provided insight into the relationships between the properties of an immunogen and the induction of the desired immune responses. We have previously utilized this approach to define the minimal structures required for the induction of antibody responses. Our more recent studies have focused on defining the parameters involved in the induction of cell-mediated and mucosal immune responses. Toward this end we have developed a new type of subunit vaccine that is effective when given orally or intramuscularly, and elucidated structure-function relationships in peptide vaccines that affect induction of CD8+ cell responses. PMID- 7865343 TI - 1994 Annual meeting of the Laboratory of Tumor Cell Biology. Rockville, Maryland, September 25-October 1, 1994. Abstracts. PMID- 7865344 TI - Purification and characterization of the bovine pituitary luteinizing hormone releasing hormone M(r) 60,000 binding protein. AB - Luteinizing hormone releasing hormone (LHRH) regulates the release of luteinizing hormone and follicle stimulating hormone from the pituitary. This process takes place through interaction with high affinity membrane receptors. In addition LHRH inhibits the growth of several cancer cell lines through the interaction with M(r) 60,000 LHRH receptors. Here we describe the purification to homogeneity of the M(r) 60,000 bovine pituitary LHRH binding protein in amounts allowing N terminal sequencing and peptide mapping. The procedure describes solubilization of luteinizing hormone releasing hormone receptors from homogenized bovine pituitaries in an active form by using the detergent Triton X-114. The receptors were retained in the Triton X-114 phase during temperature-dependent phase separation. Preparative phase separations were performed directly on solubilized bovine pituitary extracts. SDS-PAGE of the purified LHRH receptor after LHRH immobilized affinity chromatography showed the presence of a single band with M(r) 60,000. Partial sequencing of this band after trypsin digestion of gel pieces revealed unknown sequences with a possible homology to other receptors including some G-protein coupled receptors. PMID- 7865345 TI - Introduction: cytokines in the biotherapy of infectious diseases. PMID- 7865346 TI - Cytokines in the treatment of virus infections. AB - The interferon (IFN) system consists of both the formation of the various IFN proteins, and the diverse cellular responses which these induce: these result from the intracellular changes which follow their binding to a specific cell surface receptor. There is only a single human gamma, omega and beta IFN; in contrast, there are 13 closely related chemical species ("subtypes") of human alpha IFN, which are nevertheless chemically and biologically distinct. IFN preparations made from mass cultured human cells or by using recombinant DNA techniques are now readily available for clinical use. IFN have a major role in the defence of the body against virus infections. In acute virus infections, preformed exogenous IFN cannot be given soon enough to be of value. However, IFN alpha and IFN-beta have proved of considerable value in some chronic virus infections, particularly chronic virus hepatitis and chronic papillomavirus infections. The doses routinely used are associated with both acute and chronic toxic side effects. Also, some patients form specific neutralising antibodies against the particular IFN preparation injected, which may abrogate all the benefits of the treatment. Nevertheless, IFN are now established as agents for use in routine medical practice. PMID- 7865347 TI - Interleukin-1 and related pro-inflammatory cytokines in the treatment of bacterial infections in neutropenic and non-neutropenic animals. AB - Bacterial infections in the immunocompromized host cause considerable mortality, and even the recently developed antimicrobial strategies often fail to cure these infections, especially in granulocytopenic patients. Cytokines and hematopoietic growth factors have been shown to stimulate host defense mechanisms in vitro and in vivo. We discuss the possible role of the pro-inflammatory cytokines interleukin-1, tumor necrosis factor-alpha, interleukin-6 and interleukin-8 as modulators of host resistance to bacterial infections. Interleukin-1 has been shown effective in various animal models of potentially lethal bacterial infection, even during severe granulocytopenia. The protective mechanism of interleukin-1 may be mediated via downregulation of cytokine receptors and cytokine production, and via induction of acute phase proteins. Moreover, in subacute and chronic infections interleukin-1 interferes with microbial outgrowth, via mechanisms that have only been partially elucidated. PMID- 7865349 TI - Cytokines and legionellosis. AB - Recent studies have led to an enhanced understanding of the role of cell-mediated immunity and cytokines in Legionnaires' disease. In particular, the effect of interferon gamma on human mononuclear phagocyte iron metabolism and the role of iron availability of Legionella pneumophila intracellular multiplication in human monocytes has been elucidated. With this knowledge it is now possible to develop treatment strategies for Legionnaires' disease using interferon gamma and/or agents affecting human mononuclear phagocyte iron metabolism. PMID- 7865348 TI - Cytokines and the host defense against Listeria monocytogenes and Salmonella typhimurium. AB - The host defense against intracellular pathogens depends largely on activation of phagocytes and is regulated by a complex network of cytokines. Modulation of this cytokine network might lead to new or additional therapies in the treatment of infections with intracellular pathogens. Therefore, insight in the role of various cytokines in the host defense against these pathogens is required. The present contribution summarizes the results of various studies on the role of different cytokines in the host defense against the intracellular bacteria Listeria monocytogenes and Salmonella typhimurium. PMID- 7865350 TI - The role of cytokines in mycobacterial infection. AB - Mycobacterial infections are a major cause of morbidity and mortality worldwide. The pathogenesis of infection and the mechanisms for the development of protective immunity are poorly known, but cytokines appear to play an important role in the modulation of the immune response. Evidence exists for the role of tumor necrosis factor (TNF-alpha), granulocyte macrophage colony stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) in the host defense against mycobacteria. In this article we discuss recent findings about the role of cytokines in leprosy, tuberculosis and Mycobacterium avium infection, using in vitro and in vivo human and murine data. PMID- 7865351 TI - Cytokines in the treatment of fungal infections. AB - The incidence of invasive fungal infections in the immunocompromized host has increased during the past decade. Even the recently developed antifungal drugs are unable to cure these infections in patients with severely impaired host defense mechanisms. Cytokines have great potential to augment host resistance and as adjunctive therapy of invasive mycoses. We discuss the mechanisms of host defense against invasive candidiasis, aspergillosis, and cryptococcosis, and review the use of cytokines and growth factors in this setting. Interleukin-1 has been shown effective in an animal model of disseminated candidiasis, even during severe granulocytopenia. Interferon-gamma has been very effective as a modulator of resistance against a variety of fungal infections in vitro. The effect of interferon-gamma against disseminated candidiasis has been demonstrated in a mouse model. Activation of neutrophils is the main mechanism by which interferon gamma enhances the elimination of Candida, and consequently the agent is not effective in severely granulocytopenic animals. Data on the role of colony stimulating factors against fungal pathogens are accumulating, and trials with these agents for hematologic patients with invasive fungal infections are now being performed. PMID- 7865352 TI - Cytokines in malaria, pathology and protection. PMID- 7865353 TI - Cytokines in the treatment of leishmaniasis: from studies of immunopathology to patient therapy. AB - The genus Leishmania, an obligate intramacrophage parasite, causes a wide spectrum of clinical diseases. It is worldwide in distribution and causes 20 million new cases annually with an at risk population of approximately 1.5 billion persons. The most severe forms are associated with high morbidity, mortality and relapses with conventional therapy. The therapeutic issues and responses to standard and alternative therapies are reviewed. Recent developments in molecular biology and immunology methods employed in the study of leishmaniasis have defined an intricate interaction of the parasite with host immune system. Perturbation of the host immune responses may be part of the survival mechanisms of Leishmania. In murine model, the finding of T helper cells that differ by their panel of cytokines has allowed a more precise definition of immunopathogenesis of leishmaniasis. Preliminary data from leishmaniasis patients lend support to this concept of altered immunomodulation. Furthermore, the data from leishmaniasis patients lend support to this concept of altered enhancement of therapeutic response by interferon-gamma has provided a new approach for treatment of patients using recombinant cytokines and for the study of the disease. Current research for early diagnosis, alternative therapies and need for vaccines are reviewed in the context of the immunopathology of leishmaniasis. PMID- 7865354 TI - The role of cytokines in toxoplasmosis. AB - Infection with Toxoplasma gondii is normally asymptomatic, but as a consequence of the AIDS epidemic the incidence of symptomatic disease and especially toxoplasmic encephalitis (TE) has grown in frequency. The high frequency of adverse reactions to conventional therapeutic regimens for toxoplasmosis highlight the need to develop new strategies for the management of this disease. The importance of cytokines in resistance against T. gondii has been shown primarily in murine models of toxoplasmosis and a number of cytokines (e.g., IFN gamma, TNF-alpha, IL-2 and IL-12) have been proposed for trials in patients with TE. One mechanism by which these cytokines produce their effects is through stimulation of macrophages and/or NK cells. However, there are problems with immunological intervention in immunocompromised patients with TE since the infection is present primarily in the central nervous system (CNS), an immunoprivileged site, and because certain cytokines may down regulate the immune response. While much valuable information has been obtained from studies conducted in immunocompetent strains of mice their relevance to an immunocompromised host is unknown. The development of genetically altered mice with immune deficiencies offers promising new models that may allow for more rational development of new treatment regimens. PMID- 7865355 TI - Cytokines in the treatment of primary immunodeficiency. AB - Cytokines have great potential in the treatment of primary immunodeficiencies, which is just beginning to be realized. We discuss some general considerations in the use of cytokines in this setting, and review the clinical use of a number of cytokines. The best proven example to date is the use of interferon-gamma in chronic granulomatous disease, which significantly reduces infectious complications of this disease. We also discuss the potential use of interferon gamma in the hyperimmunoglobulin E syndrome and in newborns. Granulocyte-colony stimulating factor usage in congenital neutropenias is reviewed. The use of IL-2, thymic hormones, and interferon-alpha are briefly discussed. Strategies for the design of clinical trials of cytokines in these uncommon illnesses are proposed. PMID- 7865356 TI - Cytokines as potential vaccine adjuvants. AB - There is a compelling clinical need for adjuvants suitable for human use to enhance the efficacy of vaccines in the prevention of life-threatening infection. Candidate populations for such vaccine-adjuvant strategies include normal individuals at the two extremes of life, as well as the ever increasing population of immunocompromised individuals. In addition, adjuvants that would increase the efficiency of vaccination with such vaccines as those directed against hepatitis B and Streptococcus pneumoniae would have an even greater general use. Cytokines, as natural peptides intimately involved in the normal immune response, have great appeal as potential adjuvants. An increasing body of work utilizing recombinant versions of interleukin-1, -2, -3, -6, -12, gamma interferon, tumor necrosis factor, and granulocyte-monocyte-colony stimulating factor has shown that cytokines do have vaccine adjuvant activity. However, in order to optimize adjuvant effect and minimize systemic toxicity, strategies in which the cytokine is fused to the antigen, or the cytokine is presented within liposomes or microspheres appear to be necessary to make this a practical approach suitable for human use. There is much promise in this approach, but there is much work to be accomplished in order to optimize the pharmacokinetics of cytokine administration as well as its side effect profile. PMID- 7865357 TI - [Education of foreign pediatric surgeons]. PMID- 7865358 TI - [Surgical alternatives in congenital tracheal stenosis]. AB - Congenital tracheal stenosis is a rare condition with a high mortality. In a 12 year period, 5 cases (ages 5 days to 4 years) with this anomaly were treated. 4 were corrected, the operative repair consisted of segmental resection and anastomosis in one patient, and rib-cartilage tracheoplasty in the other three. The other patient died 12 days after bronchoscopy without attempt of surgical correction. Two patients died during or just after surgery, both of them presenting a similar clinical course consisting on severe air trapping, mechanical pulmonary hypertension and low cardiac output. Long-term follow-up of the survivors is satisfactory. PMID- 7865360 TI - [Neuroblastoma IV-S. A multicenter study. Work Group of Pediatric Oncology. Spanish Society of Pediatric Surgery]. AB - A retrospective multicentric study of 23 patients with stage IV-S neuroblastoma treated in 10 national Pediatric Surgery Departments between January 1988 and December 1992, is presented. All cases were classified as stage IV-S following staging criteria proposed by Evans et al. The age diagnosis was an average of 3 months. An acute clinical course was seen in 7 patients. Primary sites of the tumor were: adrenal gland in 6 patients (30.5%), abdominal paravertebral in 3 (13%) and unknown in 2 (9%). Distant tumor sites were: liver in 20 patients, bone marrow in 9, and skin in 5. There were not systematic therapeutic approach, in 16 cases (69%) the primary tumor was resected, 18 (78%) received chemotherapy, the liver was irradiated in 3 (13%), and 1 case (4%) received no treatment at all. One children died. The overall disease-free survival is 95.6% at 43 months post diagnosis. A common treatment protocol is proposed, with systematic determination of N-myc oncogene which will indicate the appropriate therapy. PMID- 7865359 TI - [Neuroblastoma with bone marrow invasion. A multicenter study. Work Group of the Spanish Society of Pediatric Surgery]. AB - By means of a retrospective study made of multiple centres, it was aimed to determine which variables could be influential at the moment of diagnosis in the prognostic of patients suffering neuroblastoma and medullary bone affection. Fifty four cases of patients belonging to a total of ten hospital centers have been revised in a period of five years. The ages under study spanned from three months to eight years of age (mean = 2.83 years). For the analysis of the patients, they were divided into two groups: one being composed of the deceased patients and the other of the surviving. The deceased patients were of a more advanced age, the delay in the diagnosis was greater, the primitive tumor was found to be more frequently located in the adrenal glands, the metastasis appeared more readily in multiples, and the effectiveness of the treatment was less, resulting in lower cases of remission and a less radical surgery. The only difference with respect to other publications is that in the case of surviving patients, the number of cases of enolase and ferritin is more frequently pathological. PMID- 7865361 TI - [Passerini-Glazel technique of vulvovaginoplasty: a solution for upper outlet of the vagina]. AB - Since 1988, we have performed the Passerini-Glazel technique, in 5 patients, between 7 months and 3 years old. All showed female pseudohermaphroditism with severe signs of masculinization, and consequently, high outlet of the vagina in the urethra, secondary to Congenital Adrenal Hyperplasia (CAH). The technique use is to get a functional and esthetically acceptable vagina at the expense of a urethral flap and two flaps of skin, coming from the hypertrophic clitoris. The results were excellent in all the patients. In one occasion it was necessary to insert a cylinder of vesical mucous to get a suture without tension of both hemivaginas. In one case there appeared a late vaginal stenosis that was solved with dilations. The present technique is indicated in those cases of CAH, with great testosterone impregnation, in which the vagina ends very high and her primary descent is difficult. It is also indicate in those cases in which there exists the risk of hurting the external sphincter, which would damage the urinary continence mechanism. PMID- 7865363 TI - [Hypospadias. Onlay technique]. AB - The "onlay" urethroplasty is based technically on the following principles: movilization of the urethral plate without dividing it, complete exeresis of chordee beneath it and use of a double faced mucocutaneous vascularized flap from the dorsal aspect rotated to the ventral aspect of penis. Several advantages over other technical modalities make its applicability possible in almost all varieties of hypospadias even in those with severe incurvature. Up to date we have used this technique in 9 patients between 2 and 3 years of age with proximal and middle hypospadias and in one with a considerable middle third fistula, without complications. PMID- 7865362 TI - [Tissue expansion in the reconstruction of post-burn lesions in childhood]. AB - Tissue expansion has gained increased acceptance in postburn reconstruction. In this study, the clinical outcome in 17 paediatric burn patients is outlined. A total of 46 tissue expanders were inserted for the reconstruction of postburn scalp alopecia (n = 11) and burn scars (n = 6). The average size of soft tissue defect was 124 cm2. Mean followup was 19 months. The overall outcome in most cases was excellent, however, complications were common (37%) and included infection, exposure, port loss, and partial flap necrosis. Five patients in the scalp reconstruction group required transfusion (45%). Tissue expansion in paediatric burn reconstruction is a useful technique which may yield superb results, however, careful surgical planning is essential to avoid complications. PMID- 7865364 TI - [Efficacy of extramucosal myotomy in an experimental model of intramural colonic obstruction. An experimental study in rats]. AB - An experimental study over the efficacy of myotomy in the treatment of intramural colon obstruction is presented. Forty Wistar rats were used. Four groups were made with ten animals each: Group I: control; Group II: myenteric denervation of four cm segment of transverse colon; Group III: myenteric denervation of 4 cm segment of transverse colon and myotomy; Group IV: myotomy of segment of transverse colon. Myenteric denervation was produced by serosal application of 0.1% benzalkonium chloride during 30 minutes. Animals were evaluated by clinical parameters (survival, weight change, food intake, nutritional state), radiological (barium enema) and Histomorphometry. The myotomy is an effective technique for the treatment of the experimental model of colon obstruction used. PMID- 7865365 TI - [Fluid dynamics in the Port-a-Cath Low Profile: therapeutic uses]. AB - The treatment of infection and obstruction in totally implantable central venous access catheters is based on the administration of medication into the system. Injected medication may be diluted in the portal which acts as a dead space in the line. We have studied the dynamic of fluids in the Low Profile Port-a-Cath, and developed an infusion-suction technique with double syringe to achieve high concentrations in the system with minimum repercussion in the vascular space. This procedure can be applied both in the treatment of infection with high-dose local antibiotics and in total or partial obstructions. PMID- 7865366 TI - [Lymphoproliferative disease in pediatric liver transplantation]. AB - Post-Transplant Lymphoproliferative Disorders are due to continuous B-lymphocyte proliferation induced by Epstein-Barr Virus (EBV) infection which is recovered in 88% of transplanted patients. These disorders may present clinically as lymphadenopathic syndrome with lymphoid tissue hyperplasia, systemic as a mononucleosis-like syndrome and lymphomatous syndrome, indistinguishable from non Hodgkin's lymphoma. We present 10 patients of PTLD classified as 7 lymphadenopathic, 1 systemic (this patient had both syndromes) and 3 lymphomatous tumours. At present, PTLD treatment consists of surgical removal of accessible masses or post-chemotherapy (ChT) tumour rests, total or partial withdrawal of immunosuppressive drugs and ChT following the Societe Francaise d'Oncologie Pediatrique (SFOP) protocol for non-Hodgkin's lymphoma. PMID- 7865367 TI - [Liver transplantation of living donors: first experiences in Spain]. AB - The shortage of pediatric donors with a significant mortality in the waiting list has moved to the development of new techniques of liver transplantation that allow the reduction in size of bigger grafts to make them fit in the abdominal cavity of the small children. The last advancement on these techniques has come with the use as a graft of a segment of liver removed from a living donor genetically related with the recipient. The preliminary studies of the candidates for living donors were started after getting an informed consent. The evaluation consisted basically in: liver function test, virological screening, chest x-ray, EKG, volumetric CT scan to ascertain liver size, doppler ultrasound, selective hepatic arteriography, anesthetic consult and psychiatric study. Two candidates were accepted as living donors. In both the segments II and III of the liver were removed. The surgical procedures of donation lasted around six hours and the two donors were discharges at the seventh day without complication. The living related liver transplant represents an option that contribute to reduce the pediatric waiting list. The advantages of this technique are: the procedure may be performed in an elective way at the time that is appropriate for the patient and providing a graft of uniformly high quality. PMID- 7865368 TI - [Obstructive candidiasis: a process with surgical solution]. AB - We describe three severe clinic cases due to fungus balls of Candida albicans in hospitalized risky patients which presented a quickly clinical evolution. Because of their different local presentations medical and surgical management was needed. In the first case a intestinal fungus ball was found whereas in the other two cases were localized in the urinary tract. Here we present their clinical findings rather than their evolution after a medical and surgical management. PMID- 7865369 TI - [Fetal cystic neuroblastoma]. AB - Neuroblastoma is the most common malignant solid tumor in infants less than 1 year old. A case of adrenal cystic neuroblastoma detected by ultrasound in the 37 th week of pregnancy, is reported. The sonographic features of fetal neuroblastoma range from solid to cystic or complex lesions. Early detection of the tumor by prenatal ultrasound permits prompt neonatal treatment and a better outcome. PMID- 7865370 TI - Myositis and myopathies. PMID- 7865371 TI - Raynaud's phenomenon, scleroderma, overlap syndromes, and other fibrosing syndromes. PMID- 7865372 TI - Myositis and myopathies. PMID- 7865373 TI - Metabolic myopathies. AB - Metabolic myopathies are disorders of muscle energy production that result in skeletal muscle dysfunction. Cardiac and systemic metabolic dysfunction may coexist. Symptoms are often intermittent and provoked by exercise or changes in supply of lipid and carbohydrate fuels. Specific disorders of lipid and carbohydrate metabolism in muscle are reviewed. Evaluation often requires provocative exercise testing. These tests may include ischemic forearm exercise, aerobic cycle exercise, and 31P magnetic resonance spectroscopy with exercise. PMID- 7865374 TI - Mitochondrial myopathies. AB - Major new advances in the genetic and biochemical characterization of mitochondrial myopathies are discussed, within a general presentation of this important new area of human pathology. Mitochondrial disorders can be due to mutations in either nuclear or mitochondrial genes involved in the synthesis of individual respiratory chain subunits or in their posttranslational control. Although no mutations of nuclear-encoded oxidative phosphorylation subunits have been reported so far in humans, numerous biochemically defined disorders are attributed to nuclear gene defects. In contrast, molecular lesions of mitochondrial DNA are recognized as an increasingly frequent cause of defective oxidative phosphorylation. Numerous new mutations recently have been identified, including both maternally inherited point mutations and sporadic large-scale rearrangements. In addition, the identification of new or overlap syndromes has substantially broadened the clinical spectrum of mitochondrial disorders. To gain insight into the pathogenesis of these disorders, the relationship between specific clinical presentations and the mitochondrial genotype has been intensively investigated. In most cases, the phenotypic expression of the mitochondrial DNA mutations depends on the interplay among the relative amount of mutated vs wild-type genomes, ie, the degree of mitochondrial heteroplasmy and its tissue and cell distribution, the reliance of the affected tissues on aerobic energy supply, the age and gender of the individual, and other still poorly understood factors including individual "nuclear genetic background" and environmental factors. PMID- 7865375 TI - Cellular aspects of myositis. AB - Polymyositis, dermatomyositis, and inclusion-body myositis are characterized by muscle cell infiltration and specific alterations on or within muscle fibers. Infiltrating immune cells (ie, T or B lymphocytes, macrophages, and natural killer cells) have distinctive distributions in these conditions: increased presence of CD8+/MHC I-restricted T lymphocytes at endomysial sites in polymyositis and more B than T lymphocytes perivascularly in muscles of dermatomyositis patients. Muscle-infiltrating T lymphocytes mainly express alpha beta T cell receptors (TCRs) in polymyositis; they also express TCRs characterized by oligoclonal V beta repertoire, with a consensus motif indicating a conventional antigen as target of the immune attack. In inclusion-body myositis, TCRs with oligoclonal V beta also are found, but no consensus motif has been identified, suggesting possible superantigen involvement in lymphocyte recruitment. Sequence analysis of TCRs in these lymphocytes has provided insight into the probable nature of the antigenic stimulus and into recruitment of these cells to the inflammation sites. T cell- or natural killer cell-mediated cytotoxic agents have been characterized by messenger RNA or protein expression in these inflammatory myopathies, and the roles of other cytokines in the inflammation processes have been determined. In vivo and in vitro studies on muscle cells have assessed their functions as target cells or antigen-presenting cells. Combined molecular and cellular immunology studies on effector and target cells are expected to clarify the pathogenetic mechanisms underlying these inflammatory myopathies in the near future. PMID- 7865376 TI - New perspectives on the idiopathic inflammatory myopathies of childhood. AB - The idiopathic inflammatory myopathies (IIMs) of childhood are a heterogenous group of rare diseases characterized by chronic skeletal muscle inflammation. Although juvenile dermatomyositis is the most common of these disorders, children may develop any of the other types of myositis that have been better studied in adults. These include not only the IIMs delineated by clinicopathologic features but also the serologic groups of myositis, recently defined by myositis-specific and myositis-associated autoantibodies. Differences in the frequencies of IIM groups between children and adults suggest differences in exposures to myositis inducing environmental agents or differences in the frequencies of susceptibility genes between these two populations. Further investigation of the heterogeneity of the childhood IIMs and of the newly described clinicopathologic and autoantibody groups should improve our understanding and treatment of these disorders. PMID- 7865377 TI - Dermatologic aspects of myositis. AB - Dermatologists have long recognized that patients occasionally exhibit the pathognomic skin changes of dermatomyositis without clinical evidence of myositis for much longer than is typical for the classic form of this disease. The term dermatomyositis sine myositis has been used to refer to this condition in the past, although there is virtually no written record of this entity in the English language medical literature. During the past 5 years, the disease course in such patients has been formally described in several case reports and small retrospective series, often under the designation amyopathic dermatomyositis. In this review, we discuss clinical issues relating to this poorly understood illness, including the possibilities of the existence of subclinical myositis, risk of occult malignancy, and risk of systemic disease manifestations normally associated with the classic form of dermatomyositis, such as interstitial lung disease. In addition, we address other issues of recent interest pertaining to the cutaneous manifestations of the inflammatory myopathies, such as unusual types of skin lesions, exacerbation of disease activity by ultraviolet light exposure, relative risk of intradermal bovine collagen injections, and management of corticosteroid-resistant skin lesions. PMID- 7865378 TI - Myositis and malignancy. AB - Dermatomyositis appears to be associated with a greater frequency of malignancy than expected in the general population. For polymyositis, there does not appear to be a greatly increased risk of malignancy. Ovarian cancer may be overrepresented in women with dermatomyositis and difficult to detect. A paraneoplastic course, in which the activity of the myositis parallels that of the malignancy, occurs in some patients but is unusual. Although the frequency of malignancy rises with increasing age, young patients may harbor malignancy. The search for malignancy should be directed by symptoms, findings on physical examination, or laboratory testing, and it should be age appropriate. PMID- 7865379 TI - Current treatment of the inflammatory myopathies. AB - Among the main concerns regarding the current therapy for the inflammatory myopathies are a lack of adequate controlled trials, a lack of objective means to reliably measure muscle strength, lack of natural history data, consideration of polymyositis, dermatomyositis, and inclusion-body myositis as a homogeneous group of inflammatory myopathies, and reliance on nonspecific markers for determining prognosis and assessing response to therapies. Prednisone remains the drug of choice in treating these disorders, although a controlled trial has never been undertaken to study its efficacy. Among the steroid-sparing agents, azathioprine, methotrexate, cyclosporine, and chlorambucil are used with invariably low to moderate success. There are no results of controlled trials to indicate whether one of these drugs is superior to another. Intravenous immunoglobulin, which is very expensive, was shown in a controlled trial to be effective in steroid resistant dermatomyositis not only in dramatically improving muscle strength and skin rash but also in resolving the underlying immunopathology. Controlled trials of intravenous immunoglobulin in patients with polymyositis and inclusion-body myositis are under way. Inclusion-body myositis has emerged as a common inflammatory myopathy that is predictably disabling and resistant to most therapies. PMID- 7865380 TI - Raynaud's phenomenon, scleroderma, overlap syndromes, and other fibrosing syndromes. PMID- 7865381 TI - Genetic and environmental factors in scleroderma. AB - Recent epidemiologic research on scleroderma has been directed toward both genetic and environmental factors. The nature of any genetic contribution is unknown, although the major histocompatibility complex region is important in determining antibody response. Environmentally, an occupational basis in a small proportion of cases seems likely. There is no evidence to support the hypothesis that silicone gel breast implants are an important risk factor in the development of scleroderma. PMID- 7865382 TI - Immunologic aspects of scleroderma. AB - Many distinct areas of investigation contribute to the understanding of immune abnormalities in systemic sclerosis. Recent immunohistochemical studies question the causal relationship of increased transforming growth factor-beta expression to dermal fibrosis. RNA polymerase I, II, and III have been identified as autoantigens specific for systemic sclerosis. Anti-RNA polymerase antibodies are directed against both unique and shared subunits of the multiprotein complexes. The targeting of several subunits suggests that the entire complexes are processed and presented by antigen-presenting cells. Genetic studies show that both HLA-DR and HLA-DQ genes control the antitopoisomerase response in Japanese patients. The null allele of the complement component C4 and HLA-DQA2 have been identified as two independent disease susceptibility genes. PMID- 7865383 TI - Connective tissue metabolism including cytokines in scleroderma. AB - The currently published literature on systemic sclerosis underscores the importance of vascular-leukocyte adhesion and perturbations of cytokines and growth factors that reflect T-cell activation and abnormal stimulation of fibroblast growth and matrix synthesis. Articles dealing with these topics are reviewed. PMID- 7865384 TI - Raynaud's phenomenon and vascular disease in scleroderma. AB - Raynaud's phenomenon is the most common sign of vascular involvement in scleroderma. Careful clinical evaluation using a simple definition of Raynaud's phenomenon is the most reliable and reproducible method in the diagnosis. The assessment of microvascular function by laboratory methods is still not specific or sensitive enough for individual patient evaluation. The study of mechanisms involved in the pathogenesis of primary and secondary Raynaud's phenomenon offers the best window for investigation of the early pathogenetic stages in scleroderma. The structural vascular disease in scleroderma is well documented. Still, the impact of endothelial involvement on organ functions is just beginning to be identified and appreciated. Dysregulation of vascular tone control and deficiency of the vasodilatory neuropeptides in scleroderma is proposed as a mechanism in the development of Raynaud's phenomenon. Decreased fibrinolysis and enhanced platelet aggregation is documented and undoubtedly contributes to microvascular thrombosis. The nature of endothelial injury is still elusive, yet markers of endothelial activation and injury continue to be described. Therapy directed toward the vascular disease continues to focus on the alleviation of vascular spasm. Calcitonin gene-related peptide is the newest agent in our therapeutic armamentarium. PMID- 7865385 TI - Clinical aspects of systemic and localized scleroderma. AB - Continued efforts are being made to better define the clinical course, disease subsets, and predictors of outcome in scleroderma. Data suggest that the course of the skin disease is triphasic, with the most active thickening phase in the first 12 months of disease. The presence of specific autoantibodies may predict clinical course more precisely than any clinical feature. Antipolymerase I, II, and III antibodies seem specific for scleroderma and, if present, may predict aggressive disease. Early detection of lung involvement provides an opportunity to select patients who may be responsive to drug treatment. Renal crisis in scleroderma is still important and may occur in the absence of significant signs of cutaneous fibrosis. Renin plasma levels do not appear helpful in predicting renal crisis. Significant gastrointestinal reflux disease with delayed acid clearance and esophagitis is associated with aperistalsis of the lower esophagus. Evidence for widespread structural and functional abnormalities of the microvascular circulation have been reemphasized. The psychosocial impact of scleroderma has been studied, demonstrating both the importance of depression and the need for social support. The etiology of localized scleroderma remains unknown despite efforts to link these lesions to Borrelia burgdorferi infection. PMID- 7865386 TI - Treatment of systemic sclerosis. AB - The treatment of systemic sclerosis remains therapeutically challenging. Until just recently, no disease-modifying intervention was proved to be effective. Over the past year, much effort has gone into setting up proposals for outcome measures and response criteria in clinical trials. Several intervention studies were published. Aminobenzoate potassium was found to be ineffective in a double blind, placebo-controlled trial. Possible efficacy for antithymocyte globulin was suggested in two small open studies, and the dispute about the use of extracorporeal photopheresis continues. The results of another open trial of methotrexate showed improvement of skin involvement in the majority of patients, and attention was drawn to the nephrotoxic side effects of cyclosporine. Combination therapy with cyclophosphamide and low-dose corticosteroids seems promising for improving pulmonary function in scleroderma patients with progressive lung involvement. Iloprost was shown to be superior to placebo in the treatment of Raynaud's phenomenon secondary to scleroderma. Anecdotal data indicate a possible beneficial effect of octreotide treatment in pseudoobstruction intestinalis due to scleroderma. PMID- 7865387 TI - Eosinophilia-myalgia syndrome, toxic-oil syndrome, and diffuse fasciitis with eosinophilia. AB - Eosinophilia-myalgia syndrome, a recently described illness, reached epidemic proportions in 1989 and was linked to the ingestion of L-tryptophan containing trace amounts of several contaminants. Eosinophilia-myalgia syndrome shares many clinical and pathologic similarities with toxic-oil syndrome, an epidemic linked to the ingestion of adulterated cooking oil that occurred in Spain in 1981, and to diffuse fasciitis with eosinophilia, a condition first described in 1974. Over the past year, much work has been done in understanding the etiology and pathogenesis of eosinophilia-myalgia syndrome and toxic-oil syndrome. Follow-up data detailing the long-term sequelae and mortality rates for these two conditions are becoming available. The results from these studies are reviewed in this paper. PMID- 7865388 TI - Overlapping syndromes, undifferentiated connective tissue disease, and other fibrosing conditions. AB - Mixed connective disease is the prototype of an overlapping connective tissue disease. Based on the presence of a specific autoantibody directed against U1 snRNP (U1 small ribonucleoprotein), the syndrome has been considered a distinct disease entity. Patients with anti-U1-snRNP antibodies, however, do not present with a homogeneous clinical syndrome, and the majority develop a classified connective tissue disease within 5 years of presentation. Signs of scleroderma predominate in most patients. The immune response resulting in anti-U1-snRNP seems antigen driven and may result from molecular mimicry between U1-snRNP and certain viral proteins. Fibrotic conditions related to extrinsic factors have been described as human adjuvant disease. Case reports suggest that Swanson silastic joint prostheses can induce granulomatous reactions at a distance from the joints due to leaking of silicone from the implants. Much attention recently has been given to the possible induction of scleroderma-like syndromes in relation to silicone gel breast implants. However, the presently available data do not show convincing evidence that women with silicone gel breast implants are significantly at risk for developing a connective tissue disease. PMID- 7865389 TI - Endoluminal aortic aneurysm repair using a balloon-expandable stent-graft device: a progress report. AB - We describe our experience with endoluminal repair of abdominal aortic aneurysms using the stent-graft device. Twenty-four patients underwent 25 procedures in the 27-month period ending December 31, 1992. Twenty-one of the patients were considered high-risk candidates for conventional surgical repair. The endoluminal stented grafts were aortoaortic in 16 procedures and unilateral aortoiliac in eight. One patient underwent a second procedure consisting of an ilioiliac graft to repair a separate common iliac artery aneurysm. Technical problems were primarily related to retrograde transluminal access across the iliac arteries, tortuous aneurysms, and misjudgments as to measurement of length. One patient died and another required secondary deployment of a distal stent at 4 months; subsequent aneurysm expansion mandated surgical replacement at 18 months. It is clear that this device and methodology will have to undergo further refinement before the technique is acceptable for wider clinical application. Current experience, however, is encouraging. Aneurysm exclusion with an endoluminal prosthesis is likely to become an important therapeutic alternative over the next several years. PMID- 7865390 TI - Proximal venous outflow obstruction in patients with upper extremity arteriovenous dialysis access. AB - To evaluate the impact of central venous obstruction on upper extremity hemodialysis access failure, we retrospectively analyzed our recent experience in managing this problem. We reviewed 158 upper extremity hemodialysis access procedures performed in 122 patients during a 1-year period. Fourteen (11.5%) patients had central vein obstruction as the cause of severe arm swelling, graft thrombosis, or graft malfunction. All 14 patients had had bilateral temporary subclavian vein dialysis catheters and failed upper extremity arteriovenous access. Seventeen lesions were treated in 14 patients including eight subclavian vein occlusions, six subclavian vein stenoses, two internal jugular vein stenoses, and one superior vena cava stenosis. Twenty-one procedures were performed including 17 percutaneous transluminal balloon angioplasties (PTAs) with stent placement in 13, two axillary to innominate vein bypasses, and two axillary to internal jugular vein bypasses. All patients had resolution of symptoms. Thirteen (76%) PTAs were initially successful but in four (24%) cases it was impossible to recanalize the vein. Eight (47%) PTAs provided functional hemodialysis access for 2 to 9 months, two (12%) restenosed at 3 and 10 months and were successfully redilated, two occluded at 2 and 4 months and were unable to be recanalized, and one failed immediately after a successful PTA. Four PTA failures were followed by venous bypass, which remained patent and provided functional access 7 to 13 months after surgery. Of nine stenotic venous lesions six (67%) were successfully dilated without restenosis, whereas of eight occluded veins only two (25%) were successfully treated without recurrence. Temporary central hemodialysis catheters produce a significant number of symptomatic central vein obstructions in patients with upper extremity arteriovenous access.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865391 TI - Healing of aortic prosthetic grafts: a study by magnetic resonance imaging. AB - Thirty-six patients with aortoiliac reconstruction were studied by magnetic resonance imaging (MRI) to determine the diameter, baseline signal, and subsequent magnetic signal characteristics of postoperative periprosthetic collection (PPC). Our study confirmed the presence of PCC in most cases (32/36). The diameter was significantly (p < 0.05) correlated with the type of disease being treated, the type of proximal anastomosis created, and whether or not drainage and postoperative transfusion were used. PPC usually disappeared within 3 to 6 months postoperatively. Modifications of magnetic signals T1 and T2 require approximately the same amount of time to diminish. During follow-up investigations in this series, there was one case of prosthetic infection characterized by the persistence of PPC and a strong T2 signal 6 months after surgery, the latter corresponding to incomplete or delayed healing. The MRI aspects of normal healing of aortic grafts were analyzed to correctly interpret the MRI aspects of complications in surgery of the aorta. PMID- 7865392 TI - Intramuscular pressures beneath elastic and inelastic leggings. AB - Leg compression devices have been used extensively by patients to combat chronic venous insufficiency and by astronauts to counteract orthostatic intolerance following spaceflight. However, the effects of elastic and inelastic leggings on the calf muscle pump have not been compared. The purpose of this study was to compare in normal subjects the effects of elastic and inelastic compression on leg intramuscular pressure (IMP), an objective index of calf muscle pump function. IMP in soleus and tibialis anterior muscles was measured with transducer-tipped catheters. Surface compression between each legging and the skin was recorded with an air bladder. Subjects were studied under three conditions: (1) control (no legging), (2) elastic legging, and (3) inelastic legging. Pressure data were recorded for each condition during recumbency, sitting, standing, walking, and running. Elastic leggings applied significantly greater surface compression during recumbency (20 +/- 1 mm Hg, mean +/- SE) than inelastic leggings (13 +/- 2 mm Hg). During recumbency, elastic leggings produced significantly higher soleus IMP of 25 +/- 1 mm Hg and tibialis anterior IMP of 28 +/- 1 mm Hg compared to 17 +/- 1 mm Hg and 20 +/- 2 mm Hg, respectively, generated by inelastic leggings and 8 +/- 1 mm Hg and 11 +/- 1 mm Hg, respectively, without leggings. During sitting, walking, and running, however, peak IMPs generated in the muscular compartments by elastic and inelastic leggings were similar. Our results suggest that elastic leg compression applied over a long period in the recumbent posture may impede microcirculation and jeopardize tissue viability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865393 TI - Subclavian vein repair in patients with an ipsilateral arteriovenous fistula. AB - Management of subclavian vein occlusive disease in persons with an ipsilateral arteriovenous fistula can be challenging. From July 1991 to May 1993, nine patients underwent direct exploration and repair of an obstructed subclavian vein following medial claviculectomy. Eight patients had polytetrafluoroethylene (PTFE) grafts; one patient had a Brescia-Cimino fistula. Intractable arm edema was the major symptom in five of eight. The site of the occlusive disease ranged from the midsubclavian vein to the proximal innominate vein. Pathology varied from a focal occluding web to a long segment of intimal fibroplasia. Five veins were occluded; four were stenotic. Surgical procedures consisted of endovenectomy and vein patch (four), endovenectomy and PTFE patch (one), resection of a focal stricture with end-to-end anastomosis (two), resection with PTFE interposition (one), and end-to-end internal jugular to subclavian vein transposition (one). Postoperative contrast venograms revealed a patent subclavian vein in eight of eight patients. One patient died postoperatively from unrelated causes; two patients died with a functioning fistula 8 and 12 months, respectively, after surgery. Two grafts were removed for infection and one deteriorated graft was abandoned because of repeated thrombosis. Only three of nine original grafts are currently in use, including one in which the ipsilateral subclavian vein rethrombosed. Although stent placement may now be the preferred treatment for subclavian vein stenosis, vein repair may still have a role in the treatment of subclavian vein occlusion, particularly in patients with a Brescia-Cimino fistula. PMID- 7865394 TI - Acute treatment of penetrating popliteal artery trauma: the importance of soft tissue injury. AB - During a 20-year period from 1973 to 1992, 109 patients underwent early operation for acute popliteal artery trauma. Clinical variables were analyzed for their association with amputation. Gunshot wounds accounted for the majority of injuries (73%), followed by shotgun wounds (18%), stab wounds (6%), iatrogenic injuries (2%), and lacerations (1%). Fasciotomies were performed selectively in 41% of patients. Seven patients (6%) lost the injured extremity despite arterial repair. The mean time from injury to arterial repair was not significantly different for patients with or without subsequent amputation (8.6 +/- 3.6 and 9.7 +/- 7.4 hours, respectively; p = 0.69). Delay in diagnosis longer than 6 or 12 hours after the injury did not increase the risk of amputation. Other factors not associated with limb loss were preoperative ischemic neurologic deficit or compartmental hypertension, concomitant fracture, and popliteal vein injury. Severe soft tissue injury (p < 0.0001) or postoperative wound sepsis (p < 0.0001) substantially increased the risk of amputation. Delayed fasciotomies were uncommon (4%) but were associated with a significantly increased risk of amputation (p < 0.0001). Vein grafting for arterial repair (p = 0.0017) and shotgun injuries (p < 0.0001) were associated with amputation to the extent that they were related to severe soft tissue injury. The degree of soft tissue trauma and subsequent infection of devitalized tissue limits the success of popliteal arterial repair. Changes in the mechanism of trauma, liberal use of four compartment fasciotomies, and aggressive management of soft tissue injury resulted in a significant decline in the amputation rate from 21% (4/19) in the first 5 years to 0% (0/39) in the last 5 years of the study. PMID- 7865395 TI - Femoral venous reflux abolished by greater saphenous vein stripping. AB - Preoperative venous duplex scanning has revealed unexpected deep venous incompetence in patients with apparently only varicose veins. Acting on the hypothesis that the deep vein reflux was secondary to deep vein dilation caused by reflux volume, the following was done. Between July 1990 and April 1993, 29 limbs in 21 patients (16 females) were examined by color-flow duplex imaging to determine valve closure by the method of van Bemmelen. Instrumentation included high-resolution ATL-9 venous interrogation using a pneumatic cuff deflation stimulus of reflux in the standing, nonweight-bearing limb. All limbs showed greater saphenous vein reflux. Twenty-nine showed superficial femoral vein reflux and of these three showed popliteal vein reflux. Duplex testing was performed by a certified vascular technologist whose interpretation was blinded as to the results of clinical examination and grading of the severity of venous insufficiency. Surgery was performed on an outpatient basis under general anesthesia using groin-to-knee removal of the greater saphenous vein by the vein inversion technique of Van Der Strict. Stab avulsion of varicose tributary veins was accomplished during the same period of anesthesia. In 27 of 29 limbs with preoperative femoral reflux, that reflux was abolished by greater saphenous stripping. In patients with popliteal reflux both femoral and popliteal reflux was abolished. Improvement of deep venous hemodynamics by ablation of superficial reflux supports the reflux circuit theory of venous overload. Furthermore, preoperative evaluation of venous hemodynamics by duplex scanning appears to provide useful pre- and postoperative information regarding venous insufficiency in individual patients. PMID- 7865396 TI - Intraoperative measurement of Javid shunt flow with transit-time ultrasound. AB - Transit-time ultrasound methods were used to measure blood flow in 37 patients undergoing carotid endarterectomy. Internal carotid flow before (ICFbef) and after (ICFaft) endarterectomy was measured with a 6 mm perivascular probe, and Javid shunt flow (SF) was measured with a clamp-on probe. For the entire group ICFbef averaged 117 +/- 67 ml/min and ICFaft was 173 +/- 67 ml/min. Shunt flow averaged 123 +/- 51 ml/min. The differences between ICFbef and ICFaft and between SF and ICFaft were significant (ANOVA, p < 0.01) but the difference between ICFbef and SF was not. The relationship between ICFbef and SF appeared to define two groups of patients. Those in whom SF was greater than ICFbef (SF > ICFbef) had more stenosis evident on preoperative arteriograms (64.7% +/- 14.55% maximum single diameter stenosis) and a greater average increase in ICF (151% +/- 159%) than those with SF < or = ICFbef (43.3% +/- 20.9% stenosis and 34% +/- 54% increase in ICF), suggesting that the relationship between SF and ICFbef defines groups with different hemodynamic responses. The similarity between SF and ICFbef indicates that Javid shunt flow offers adequate protection from cerebral ischemia. A practical benefit of the shunt clamp-on flow probe is the ability afforded to recognize shunt occlusions. PMID- 7865397 TI - Ischemic monomelic neuropathy: an under-recognized complication of hemodialysis access. AB - During the past 3 years six episodes of ischemic monomelic neuropathy (IMN) have been identified in five patients as a complication of upper extremity dialysis grafts. All patients had long-standing insulin-dependent diabetes, peripheral neuropathy, and brachial artery graft origins, whereas 60% had peripheral vascular disease. Five episodes occurred immediately after graft placement, whereas one was due to a graft-related thromboembolus. Diagnostic delay was common with initial findings attributed to anesthesia, positioning, or surgical trauma. Electrophysiologic studies showed underlying diabetic neuropathy with severe multifocal neuropathy distal to the grafts. Digital pressure indices were reduced but there was no critical ischemia. In three cases ischemia was completely corrected with improvement in one. One patient had proximal balloon angioplasty with no improvement and of the two untreated patients, one improved slightly. Ischemic monomelic neuropathy is a rare but disabling complication of dialysis access in diabetic uremic patients. Its occurrence is unpredictable and diagnostic delay is common. Correction of ischemia is indicated but usually does not improve the neuropathy. Prevention requires further research to more accurately characterize the patients at risk. PMID- 7865398 TI - Catheter-directed thrombolysis following vena cava filtration for severe deep venous thrombosis. AB - Massive deep venous thrombosis with marked venous outflow obstruction can result in limb loss or end-organ injury. Systemically administered drugs may not reach thrombi in therapeutic concentrations and surgical and thrombolytic strategies carry a small but real risk of pulmonary embolus--similar to the risks with anticoagulation alone. We therefore developed a strategy in which catheter directed thrombolysis was used to deliver high concentrations of a plasminogen activator directly to the thrombus combined with placement of a downstream Greenfield filter to protect patients from pulmonary embolus. From 1984 to 1993 six patients were treated with this regimen. All had severe symptoms of less than 4 days' duration. On radiologic evaluation four patients had large iliofemoral and/or inferior vena cava thrombosis, one had subclavian/innominate vein thrombosis, and one had transplant renal vein/iliofemoral/inferior vena cava thrombosis. A Greenfield filter was first placed downstream prior to imbedding an infusion catheter in the greatest mass of thrombus for subsequent infusion of urokinase (n = 4) or streptokinase (n = 2). In four patients the catheter traversed the Greenfield filter. All patients were given bolus lytic therapy followed by maintenance infusions ranging in duration from 24 hours to 12 days. Five patients remained on heparin simultaneously. Clot lysis was achieved in all patients with hemodynamic, symptomatic, and arteriographic improvement. There were no deaths, pulmonary emboli, or complications of filter placement. One patient had minor bleeding at the puncture site and another had catheter-related infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865399 TI - Acute lower limb ischemia complicating endocarditis due to Candida parapsilosis in a drug abuser. AB - Acute ischemia due to arterial embolism occurred in the right leg of a male drug abuser who had developed fungal endocarditis as a result of Candida parapsilosis. Transesophageal echocardiography aided in the diagnosis. The patient was successfully treated with fibrinolysis and surgery. The clinical features and management of this serious condition have been reviewed in the literature. PMID- 7865400 TI - Carotid body tumor associated with hyperparathyroidism. AB - Hyperparathyroidism in association with carotid body tumor is a rare combination. A common embryologic cellular origin was postulated previously to explain this unusual occurrence. We report a case of left carotid body tumor and left inferior parathyroid adenoma. We believe this to be the sixth reported case in the literature with this combination. PMID- 7865401 TI - Alternative approaches to the deep femoral, popliteal, and infrapopliteal arteries in the leg and foot: Part II. PMID- 7865402 TI - Lateral approach to femoral bifurcation. AB - Femoral bifurcation can be approached through a lateral incision in the femoral triangle, passing behind the sartorius muscle and thus leaving undisturbed the femoral lymphatic network. The principal advantage of this route is it limits the local complications that occasionally result in infection of the operative site. This lateral approach is indicated primarily for infrainguinal revascularizations originating from the common femoral artery in patients at high risk for local infection. It should not, however, be used routinely because exposure of the vessels, particularly the medial aspect of the artery and the profundus vessels, is limited. The risks of this route are essentially related to the neural elements encountered during dissection. PMID- 7865403 TI - Peripheral vascular involvement in heart transplant patients. PMID- 7865404 TI - Dracunculiasis eradication. Update: 1994. PMID- 7865405 TI - Expanded programme on immunization. Measles outbreak in N'Djamena. PMID- 7865406 TI - Isolated head injuries versus multiple trauma in pediatric patients: do the same indications for cervical spine evaluation apply? AB - Although the recommendations to evaluate possible cervical spine injuries in patients with isolated head injuries are identical to those with multiple trauma, to date, no such study has confirmed that risk factors are the same for both injuries. We reviewed the charts of 268 pediatric patients with isolated head injuries admitted to the Intensive Care Unit at Children's Hospital Medical Center (1985-1990) to determine which risk factors were present. In this retrospective study, we divided the patients into two groups: low risk and high risk. The low-risk patients (n = 135) were those capable of verbal communication who did not report cervical discomfort. The high-risk patients (n = 133) either were incapable of verbal communication (preverbal or physically unable due to head injury) or reported neck pain. All patients under 2 years of age were considered preverbal and at high risk. The patients in both groups were indistinguishable by age, sex, mechanism of injury, and type of injury sustained. No patient in the low-risk group suffered cervical spine injury. Cervical spine trauma was present in 10 (7.5%) high-risk patients. Using the method of adjusted odds ratio, we found that high-risk patients had 23 times the likelihood of neck injury when compared with low-risk patients (p = 0.003, 95% confidence limit). Our results indicate that cervical spine X-rays (i.e., anteroposterior, odontoid, lateral views) are indicated only in high-risk pediatric patients with head injuries who either complain of neck pain or cannot voice such complaints because of significant head injury or preverbal age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865407 TI - Effects of ventricular drainage and dural closure on cerebrospinal fluid leaks after posterior fossa tumor surgery. AB - In a retrospective study of 50 consecutive children with posterior fossa tumors treated at Texas Children's Hospital, Houston, Tex., in 1989-1992, we evaluated perioperative factors which might influence the development of postoperative cerebrospinal fluid leaks. Factors analyzed included the presence of preoperative hydrocephalus, the institution of cerebrospinal fluid diversion, and the method of dural closure. No statistically significant impact on subsequent cerebrospinal fluid leakage was demonstrated. PMID- 7865408 TI - Primary central nervous system malignant rhabdoid tumor: CT and MR appearance simulates a primitive neuroectodermal tumor. AB - Malignant rhabdoid tumor was originally described and is most commonly reported in the kidney [1-5]. A case of primary central nervous system malignant rhabdoid tumor is presented. The clinical and pathologic findings are presented and the computed tomography and magnetic resonance imaging findings are described. PMID- 7865409 TI - Replacement laminoplasty in selective dorsal rhizotomy: possible protection against the development of musculoskeletal pain. AB - The authors present a retrospective review of 35 patients who underwent selective dorsal rhizotomy between 1990 and 1992. The first 15 patients underwent laminectomy from L1 to the sacrum without replacement of the posterior elements. The subsequent 20 patients had the laminae replaced during wound closure. No patient in either group developed spinal instability or symptomatic deformity. However, 4 patients in the first group (mean follow-up period 35 months) developed significant low-back pain of musculoskeletal origin following minor accidents (mean time to injury 12 months). No patients in the group in whom the laminae were replaced (mean follow-up period 24 months) developed back pain. This review suggests that although the lumbar laminae are not essential for the structural integrity of the spine, their removal may predispose to musculoskeletal injury and associated pain. The authors propose a mechanism for these findings and recommend replacement of the posterior elements when possible. PMID- 7865410 TI - Regressing intracranial carotid occlusions in childhood. AB - Though detected with increasing frequency, intracranial carotid artery dissection remains less common in infancy. We report on 3 otherwise healthy children aged 8, 12 and 15 years who presented with focal headache and stroke secondary to intracranial carotid occlusive disease consistent with arterial dissection. In 2 cases this was precipitated by strenuous physical exertion. The protean angiographic configuration included long tapered narrowing with focal stenosis, beaded narrowing with Moya Moya vascular network and 'string sign'; occlusion of the anterior cerebral artery was always present. Control angiograms revealed complete or partial recanalization in all cases suggesting self-healing dissection. The clinical course was smooth in all patients, and at long-term follow-up (5, 3, and 2 years) they remain in good neurological condition. Although intracranial carotid dissection has a poor reputation, regression to normal and fair outcome may sometimes occur as in the extracranial counterpart, suggesting the existence of benign forms of the disease. Surgical procedures should be weighed against the spontaneous resolution of the lesion. PMID- 7865412 TI - Childhood optic pathway tumors associated with ascites following ventriculoperitoneal shunt placement. AB - Three children with optic pathway gliomas who developed ascites following ventriculoperitoneal shunt placement are presented. In all 3 cases there was an elevated cerebrospinal fluid (CSF) protein level at the time of initial shunt placement. At the time of developing ascites following placement of the ventriculoperitoneal shunt, none of the patients had evidence of infection or tumor seeding in the peritoneal cavity. The ascites completely resolved in each instance after converting the shunt to a ventriculoatrial system. Ascites following ventriculoperitoneal shunt insertion is an uncommon complication. A review of the literature and discussion of the possible etiologic factors in the development of ascites after ventriculoperitoneal shunt placement are presented. For patients diagnosed with optic gliomas, it is suggested that because the tumor is widely exposed to the CSF space, protein exuded by the mass into the subarachnoid space will cause an elevated CSF protein concentration. The elevated CSF protein may then lead to ascites as a result of poor absorption of CSF in the peritoneal cavity after placement of a ventriculoperitoneal shunt. Although ascites following ventriculoperitoneal shunt placement is not typical in patients with optic gliomas, attention should be given to CSF protein levels documented at the time of CSF diversion for hydrocephalus, recognizing that ascites may occur as a result of poor CSF absorption in the periotoneum, subsequently requiring a ventriculoatrial shunt in patients who develop hydrocephalus. PMID- 7865411 TI - Circuit diagram of the circulation of cerebrospinal fluid. 1989. PMID- 7865413 TI - Osteoblastoma of the odontoid process. AB - A case of an osteoblastoma located in the odontoid process in a 7 year-old boy who presented with torticollis is reported. CT scan and MRI disclosed the lesion, but diagnosis was established by a CT-guided needle biopsy. Surgery through a transoral approach allowed total excision of the tumor. This is, to our knowledge, the first case reported of an osteoblastoma of the odontoid process. PMID- 7865414 TI - 6th International Symposium on Pediatric Neuro-Oncology. Houston, Texas, May 18 21, 1994. Abstracts. Part III. PMID- 7865415 TI - Class II malocclusion in mixed dentition. AB - The primary goal of early treatment is to correct the existing muscular, skeletal and dental imbalances before the eruption of the permanent teeth. When early treatment is instituted, 80% of the malocclusion can be treated with orthopedic appliances and the remaining 20% solved with the straight wire appliances. This approach ensures that in excess of 95% of the cases can be treated non-extraction and non-surgically. PMID- 7865416 TI - Enhancement of fissure sealant penetration and adaptation: the enameloplasty technique. AB - The purpose of this study was to evaluate with the scanning electron microscope (SEM) the effects of mechanically enlarging the occlusal fissures with a bur in regards to: (1) fissure micromorphology; (2) sealant penetration into fissures; and (3) micromorphology of the fitting surface of sealants. The technique is described as EST, for Enameloplasty Sealant Technique. The conventional sealant technique is referred to as CST. A total of 30 extracted permanent molars were used and divided into four groups: (1) pumice prophylaxis, no sealant; (2) same as Group 1 but with FluoroShield sealant; (3) EST, no sealant; (4) EST followed by FluoroShield. Subgroups were instituted to evaluate the sealant-enamel interface and the sealant fitting surface. The bur used in this, study was specifically designed for this purpose. Some samples were replicated in epoxy resin and all samples were evaluated with the SEM. The results demonstrated that the EST allowed a deeper sealant penetration and a superior sealant adaptation than the CST. An increased surface area for sealant retention was readily evident in all samples treated with the EST. PMID- 7865417 TI - A comparative study between the double-headed toothbrush and the single headed toothbrush in plaque removal efficiency. AB - A three-way blind cross-over study was done to compare the plaque removing effects of a double-headed toothbrush with a popular single-headed toothbrush in 30 patients. Both brushes were used with the modified Bass technique for one week each. The results of this study indicated that the double-headed toothbrush is more effective in plaque removal especially when dentifrices were used. PMID- 7865418 TI - Evaluation of fissure sealants retention following four different isolation and surface preparation techniques: four years clinical trial. AB - The purpose of this study was to evaluate the retention of fissure sealants, applied with 4 different combinations of isolation and preparation of occlusal surface. In 95 children aged 7-8 years, having all four first permanent molars fully erupted and caries free, a chemically initiated tinted fissure sealant was placed with the following 4 different methods in every child. 1) Tooth 16: Cotton rolls isolation and cleaning of occlusal surface using a bristle brush and non fluoridated paste. 2) Tooth 26: Rubber dam isolation and mechanical preparation of pits and fissures using a round bur No. 0 in a slow hand-piece. 3) Tooth 36: Rubber dam isolation and cleaning of occlusal surface using a bristle brush and non-fluoridated paste. 4) Tooth 46: Isolation with cotton rolls and mechanical preparation of pits and fissures using a round bur No. 0 in a slow hand-piece. Eighty children were available for re-examination 4 years later (320 teeth). The 4 methods of application showed the following success rates of full retention: 1) 81% 2) 88% 3) 91% 4) 93%. Although statistical analysis of the results revealed only marginal statistically significant difference among the four different methods of application (p = 0.091), there was statistical significant difference (p = 0.031) between methods 1 and 4. No differences were detected among the remaining methods. The present trial revealed best sealant retention using a combination of cotton rolls isolation and mechanical preparation of the occlusal surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865419 TI - Comparison of treatment results with the edgewise and the Begg approach. AB - In order to compare the changes observed in the skeletal and the dentoalveolar elements after treatment with the edgewise and the Begg technique, fifty cases were selected and divided into two groups. Each group consisted of twenty-five patients matched in age and sex, who were treated nonextraction for the correction of Class II Division 1 malocclusion. The lateral cephalometric radiograph taken before and after treatment period were used. Twenty-four measurements were performed on each radiograph and were analyzed statistically. The first part of the evaluation aimed at comparing each group to itself before and after treatment. Concerning the skeletal elements the results were the same in the two groups: a) the anteroposterior size of the upper jaw was decreased, b) the length of the lower jaw was increased and c) there was an increase in the lower facial height. Importantly, more dentoskeletal changes were found in the Begg group. The second part of the evaluation which aimed at comparing the differences of the means (initial-final) between the two groups revealed that: 1) the chin was in a more forward position in the edgewise group, 2) there was a larger increase in the length of the lower jaw in the same group, 3) the lower facial height was increased especially in the Begg group and 4) in the edgewise group a labial inclination of the lower incisors was found, while in the Begg group a lingual inclination of the upper and a labial inclination of the lower front teeth was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865420 TI - Direct bonding brackets: unfilled versus unfilled/filled resins. AB - The clinical and clinical/laboratorial performance of unfilled/filled and only unfilled resins for direct bonding of orthodontic brackets were evaluated. In the clinical part, brackets were bonded using both techniques in alternate quadrants of eleven patients of the Orthodontic Clinic, State University of Rio de Janeiro. A total of 118 teeth, 59 in each group, were tested and bond failure frequencies were recorded for six months. For the clinical/laboratory part, upper and lower premolars to be extracted for orthodontic reasons, were selected. Thirty-two brackets were bonded in vivo--16 using unfilled/filled and 16 using only unfilled resins--and the teeth were kept in the mouth for two months. After extraction, the teeth were secured in plastic rings and an Universal Instron Machine was used to debond the brackets. No statistically significant differences were observed for clinical failure rates, nor for laboratory debonding strength between the two techniques. Failures occurred preponderantly at the bracket/resin interface, so that most of the resin remained bonded to the enamel surface on both groups. PMID- 7865421 TI - Gluma bond strength to the dentin of primary molars. AB - The purposes of this study were to measure and compare etching patterns, tensile bond strengths and fracture patterns of Gluma/Lumifor system to the buccal dentin of primary molars following application of Gluma cleanser and 37% phosphoric acid. The tensile bond strength of Gluma/Lumifor to the buccal dentin following application of Gluma cleanser averaged 5.53 +/- 3.27 (x +/- SD MPa) which is significantly greater than bond strength following application of only 37% phosphoric acid 2.04 +/- 0.67. Etching ground buccal dentin surfaces with 37% phosphoric acid has no significant different effect on the bond strength of Gluma/Lumifor combination. Gluma cleanser showed effective removal of the smear layer and partial plugging of the dentinal tubules, while 37% phosphoric acid showed complete removal of the smear layer creating opened dentinal tubules. PMID- 7865422 TI - Measurement of masseter and temporalis muscle thickness using ultrasonographic technique. AB - Ultrasonography was found to be a highly reliable and accurate method for imaging and measuring masticatory muscle thickness. No age and sex related variations were observed in this study on comparisons between the two groups. Similarly no changes were seen in the muscle thickness and different facial morphologies. Since no earlier studies on this type of investigation was done, it will be too premature to give a final verdict on the correlation between the masticatory muscle thickness and facial morphology for all the recorded cases. A long term follow up will provide a wealth of information for future clinical purposes. No age and sex related variations were observed in this study on comparisons between the two groups. Similarly no changes were seen in the muscle thickness and different facial morphologies. PMID- 7865423 TI - Subgingival bacteria in a case of prepubertal periodontitis, before and one year after extractions of the affected primary teeth. AB - The treatment of children with prepubertal periodontitis (PP), may be complicated by the extent of the lesions and the possibility of tetracycline stain of the developing permanent dentition. Therefore, with the purpose of preventing the infection of permanent teeth during the mixed dentition, it has been recommended that the treatment of children with PP, should include the early extraction of the primary teeth affected with alveolar bone loss (ABL). Still, there is little evidence which confirms that extraction of the affected primary teeth do in fact reduce the periodonto-pathogens load of the subgingival plaque. The present study reports values of colony forming units (CFU) of total anaerobic bacteria, Actinobacillus actynomicetemcomitans (Aa) and Porphyromonas gingivalis (Pg) from the subgingival plaque from a child with PP, collected immediately before and 1 year after extractions of the primary teeth affected with ABL. CFU of Aa and Pg developed only from the subgingival plaque collected before the extraction of the primary teeth affected with ABL. These findings suggest that in cases of PP, extraction of the affected primary teeth may reduce the possibility of infection of the periodontum of the permanent teeth during the mixed dentition period. PMID- 7865425 TI - Dental and craniofacial findings in a child affected by glycogen storage disease type III. AB - This paper reports on previously undescribed dentofacial features a child suffering from Glycogen-Storage Disease type III with hepatomegaly and hypertransaminasemia with muscular involvement. Deficient craniofacial development, reduced width of the upper jaw resulting in posterior cross-bite, and taurodontism of the primary dentition were found. Pathogenetic basis for craniofacial abnormalities is discussed. Cooperation between pediatricians and pediatric dentists is strongly recommended for an early diagnosis and treatment of the dentofacial defects of the syndrome. PMID- 7865424 TI - Oral findings, treatment and follow-up of a case with major aphthous stomatitis (Sutton's disease). AB - Major aphthous stomatitis (Sutton's disease) is a clinical variant of recurrent aphthous stomatitis, which is noted for its high morbidity. Since the etiology of the disease is not clear, many therapies have been attempted. However, the controversial results hinder the adoption of a single mode of management. We present a 13-year-old boy with Sutton's disease, who was successfully treated with a combination of burst systemic prednisone (1 mg/kg/day for five days, thereafter half dose on alternate days for one week) and topical triamcinolone (four rinses a day). He continued the mouth rinses with the same interval. At the end of the first month, significant healing was observed and gradual tapering was recommended on the condition that the ulcers were well-controlled. The maintenance of steroid rinse once a day provided a symptom-free period of one year. Neither any withdrawal signs nor side affects were observed. Therefore, we think that this regimen should be considered as the treatment of choice in Sutton's disease along with a close follow-up even in childhood. PMID- 7865426 TI - Sexual homicide with HIV in a Florida dental office? PMID- 7865427 TI - Process or product: how do you run your practice? PMID- 7865428 TI - Single-agent use of Taxol (paclitaxel) in breast cancer. AB - The search for new active agents and strategies to improve the prognosis for patients with stage IV breast cancer has led to examination of paclitaxel. Several clinical trials have been undertaken to determine its optimal use and clarify its role in the treatment of breast cancer and other malignancies. Several phase II trials involving breast cancer patients with limited prior therapy have yielded overall response rates (complete response and partial response) of 44% to 62% among women receiving paclitaxel. Treatment was generally well tolerated, with febrile neutropenia the most common side effect. An interim analysis of the European-Canadian Randomized Trial in Metastatic Breast Cancer demonstrated safety and efficacy of paclitaxel in a multicenter setting. Among the 234 patients evaluable for response, 29% (34/117) responded at 175 mg/m2 paclitaxel and 22% responded (26/117) at 135 mg/m2. Treatment was well tolerated at both dose levels; responses continue to evolve in patients who remain on study. Among patients with extensive prior therapy (> 2 prior regimens for stage IV disease), paclitaxel also has demonstrated safety and efficacy. At Memorial Sloan-Kettering Cancer Center, responses were noted among 36% of patients who had received two prior treatments and 21% of those who had received 3 or more. Paclitaxel was administered at 200 mg/m2 plus G-CSF. Other studies involving heavily pretreated patients yielded overall response rates as high as 53%. The concerns about cross-resistance between paclitaxel and doxorubicin (or other agents for which resistance is thought to be at least partly due to P glycoprotein-mediated pleiotropic drug resistance) also are addressed. PMID- 7865429 TI - Combination chemotherapy with Taxol (paclitaxel) in metastatic breast cancer. AB - In three phase I trials reported in the United States, the combination of paclitaxel and doxorubicin has been evaluated in previously untreated patients with metastic breast cancer. At M.D. Anderson Cancer Center, escalating doses of paclitaxel followed by a fixed dose of doxorubicin led to one complete remission (CR) and seven partial remissions (PRs) in 10 patients. Dose-limiting toxic effects were stomatitis and neutropenic fever. The maximum tolerated dose (MTD) was paclitaxel 125 mg/m2 and doxorubicin 48 mg/m2-lower than the starting dose. The reverse sequence (doxorubicin followed by paclitaxel) also was investigated to evaluate the possibility of schedule-dependent toxicity. The MTD of this reverse sequence was doxorubicin 60 mg/m2 and paclitaxel 150 mg/m2, with neutropenic fever as the dose-limiting toxicity. In a study by the National Cancer Institute (NCI), paclitaxel and doxorubicin were given simultaneously over 72 hours and doses of each were escalated resulting in two separate MTDs: paclitaxel/doxorubicin 160/75 and 180/60 mg/m2. Objective responses were 6% CR and 56% PR, and gastrointestinal disturbances were dose-limiting. Schedule dependence also was addressed in a study at Indiana University, where the drug sequence was alternated for comparison both between and across patients. Preliminary results showed an increase in mucositis when paclitaxel was given before doxorubicin. It is concluded that this is an active combination and that schedule-dependent mucositis can be avoided if doxorubicin is given first. Myelosuppression is dose-limiting, even with granulocyte colony-stimulating factor, and thrombocytopenia occurs with multiple courses. PMID- 7865430 TI - Review of phase II trials of Taxol (paclitaxel) in patients with advanced ovarian cancer. AB - The efficacy and safety of paclitaxel in the treatment of advanced ovarian cancer has been assessed in several phase II trials. McGuire and associates at the Johns Hopkins Oncology Cancer reported results from a phase II trial in which paclitaxel-administered as a 24-hour intravenous (i.v.) infusion with premedication to avoid acute hypersensitivity reactions-yielded one complete response (CR) and 11 partial responses (PRs) (overall response rate, 30%) among 40 previously treated patients with ovarian cancer evaluable for response; 25 of the patients had been refractory to cisplatin therapy. Among 30 evaluable patients who took part in a study at the Albert Einstein Cancer Center, paclitaxel (180 to 250 mg/m2 as a 24-hour i.v. infusion every 21-28 days) produced an overall response rate of 20% (1 CR, 5 PRs). Four responding patients were resistant to previous cisplatin therapy. Median survival for responders was 27 months, and 6 months for nonresponders (P = 0.0001). The Gynecologic Oncology Group confirmed the activity of paclitaxel (175 mg/m2 as a continuous 24-hour i.v. infusion) in 41 evaluable cisplatin-resistant patients, among whom 15 (37%) responded (5 CR, 10 PR). A total of 8 of 27 (29%) patients with cisplatin refractory disease responded (2/27 CR, 6/27 PR). Among 14 patients whose disease progressed more than 6 months following cisplatin therapy, 3 had CRs and 4 had PRs. Finally, the National Cancer Institute Treatment Referral Center protocol enrolled more than 2,000 patients; preliminary analysis of 1,000 patients included 663 evaluable for response with measurable disease. There are 27 CRs and 119 PRs; median time to progression for responding patients is 7 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865431 TI - Taxol (paclitaxel): mechanisms of action. AB - Paclitaxel, an antitumor drug that is demonstrating encouraging activity in human malignancies, is likely to play a major role in cancer chemotherapy. Paclitaxel has an unusual chemical structure--it is a complex diterpene having a taxane ring with a four-membered oxetane ring and an ester side chain at position C-13--and a unique mechanism of action. In vitro, paclitaxel enhances the polymerization of tubulin to stable microtubules and also interacts directly with microtubules, stabilizing them against depolymerization by cold and calcium, which readily depolymerize normal microtubules. The fact that the drug has a specific binding site on the microtubule polymer makes it unique among chemotherapeutic agents, and the ability of paclitaxel to polymerize tubulin in the absence of cofactors like guanosine triphosphate and microtubule-associated proteins is unusual. When paclitaxel and microtubule protein are irradiated with ultraviolet light, the drug preferentially binds covalently to the beta-subunit of tubulin. Paclitaxel binds to cells in a specific and saturable manner with a single set of high affinity binding sites. The microtubule cytoskeleton is reorganized in the presence of paclitaxel and extensive parallel arrays or stable bundles of microtubules are formed in cells growing in tissue culture. Paclitaxel blocks cells in the G2/M phase of the cell cycle and such cells are unable to form a normal mitotic apparatus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865432 TI - Taxol (paclitaxel) safety in patients with platinum pretreated ovarian carcinoma: an interim analysis of a phase II multicenter study. AB - The objective of this phase II, multicenter, prospective study was to evaluate the safety and the response rate of paclitaxel administered to patients with ovarian cancer. Eligible patients had histologically proven ovarian carcinoma and measurable or evaluable disease and had received at least one platinum-containing regimen and no more than three prior chemotherapy regimens. Paclitaxel was given as a continuous intravenous (i.v.) infusion over 3 hours every 3 weeks. Dose was determined by the number of prior chemotherapy regimens. Patients with one or two prior chemotherapy regimens received 175 mg/m2 (group A) and patients with three prior chemotherapy regimens 135 mg/m2 paclitaxel (group B) after premedication. Treatment was repeated every 3 weeks. An interim safety analysis for the first 99 evaluable patients, 72 treated with 175 mg/m2 and 27 treated with 135 mg/m2 paclitaxel, is reported here. Median number of courses analyzed per patient was four (range, 1 to 6) in the two groups, for a total of 393 courses evaluable for toxicity (286 in group A, 107 in group B). World Health Organization (WHO) grade 3-4 neutropenia was observed in 29.6% of courses in group A and in 23.3% in group B. Two group A patients, 1 at courses 3 and 4 and 1 at course 6, experienced WHO grade 2 fever or infection associated with a WHO grade 4 neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865433 TI - Carboplatin and Taxol (paclitaxel) in advanced ovarian carcinoma. AB - Addressing the need for more effective, less toxic therapies for patients with advanced ovarian cancer, a pilot study was conducted to evaluate the therapeutic potential of combination carboplatin/paclitaxel in previously untreated patients. Several factors provided the rationale for this study: paclitaxel plus cisplatin has been shown to be superior to standard treatment with cyclophosphamide plus cisplatin; carboplatin is equally effective and less toxic than cisplatin in ovarian cancer; paclitaxel plus carboplatin could potentially produce less nonhematologic toxicity than cisplatin plus paclitaxel; dosing of carboplatin based on the area under the carboplatin plasma concentration vs. time curve (AUC) would produce an acceptable degree of thrombocytopenia; and the potential additive neutropenia of carboplatin plus paclitaxel could be managed with the addition of growth factors. This study was designed in two parts: In part I, a fixed dose of paclitaxel (135 mg/m2 by 24-hour infusion every 21 days) was administered to study patients given escalating doses of carboplatin, beginning at an AUC of 5 and increasing to 7.5 and then to 10. Dose escalation was based on toxicity observed in the first treatment cycle, with granulocyte colony stimulating factor added when dose-limiting toxicity developed. The second part was designed to evaluate carboplatin at the maximum tolerated dose with escalating doses of paclitaxel. Preliminary results of phase I of this study indicate that paclitaxel plus carboplatin can be combined at doses that encompass the therapeutic range of carboplatin given with paclitaxel 135 mg/m2. Subsequent phases of this trial are currently under way. PMID- 7865434 TI - Taxol (paclitaxel) in the treatment of lung cancer: the Eastern Cooperative Oncology Group experience. AB - Two phase II studies of paclitaxel involving patients with advanced non-small cell lung cancer (NSCLC) have been completed. The first study, conducted by the Eastern Cooperative Oncology Group (ECOG), involved 25 previously untreated patients who received intravenous (i.v.) paclitaxel 250 mg/m2 over 24 hours every 3 weeks. Among 24 evaluable patients with stage IV disease, 5 partial responses (21%) were observed, median survival was 24.1 weeks, and 1-year survival was approximately 45%. Common toxicities included leukopenia (66% grade 4), neurotoxicity (28% grade 3), and cardiotoxicity (12.5% grade 3). The second trial, conducted at the M.D. Anderson Cancer Center, yielded similar results. Twenty-seven previously untreated patients with stage IV disease received paclitaxel 200 to 250 mg/m2 i.v. over 24 hours every 3 weeks, yielding 1 complete response and 5 partial responses (24%) in 25 evaluable patients. The major toxicity was leukopenia. No cardiac toxicity was seen. For the past several years ECOG has tested several agents against previously untreated NSCLC, and none has demonstrated a response rate greater than 10%, other than paclitaxel. Given these results, the ECOG plans to conduct a three-arm phase III study involving patients with advanced NSCLC comparing 'standard' cisplatin/etoposide chemotherapy to two paclitaxel-containing arms: (1) paclitaxel 135 mg/m2 i.v. over 24 hours plus cisplatin 75 mg/m2 i.v.; (2) paclitaxel 250 mg/m2 i.v. over 24 hours plus cisplatin 75 mg/m2 i.v. plus recombinant human granulocyte colony-stimulating factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865435 TI - Current and future trials of Taxol (paclitaxel) in head and neck cancer. AB - Phase II clinical trials of single-agent paclitaxel have demonstrated the drug's activity in ovarian cancer, breast cancer, and both small cell and non-small cell lung cancer. A recently completed trial in recurrent head and neck cancerpatients conducted by the Eastern Cooperative Oncology Group resulted in a 40% (12 of 30) overall (complete plus partial) response rate with a high dose of paclitaxel (250 mg/m2 by 24-hour continuous infusion) and granulocyte colony-stimulating factor support. Responses were observed in previously irradiated sites of locoregional disease as well as in distant metastases. The major toxicities were brief grade 3 4 neutropenia occurring in 91%, peripheral neuropathy in 39%, and arthralgias/myalgias in 39% of treated patients. Confirmatory single-agent trials with paclitaxel are in progress in the United States and Europe. Phase I and II trials also in progress or planned combine paclitaxel with cisplatin or carboplatin; ifosfamide; methotrexate; and cisplatin/5-fluorouracil. Lower doses (135 to 175 mg/m2) and alternative infusion schedules ranging from 3 hours to 10 days are also under evaluation in head and neck cancer and other solid tumors. Studies combining paclitaxel and radiotherapy are reviewed as well. PMID- 7865436 TI - Intraperitoneal Taxol (paclitaxel) in the management of ovarian cancer. AB - In an effort to examine the safety and pharmacology of the intraperitoneal (i.p.) delivery of paclitaxel, 25 patients (24 with ovarian cancer) were treated in a phase I dose escalation trial. The drug was administered in normal saline every 3 to 4 weeks, starting at a dose of 25 mg/m2. The dose-limiting toxicity at doses at or above 175 mg/m2 was abdominal pain. A 3-log pharmacokinetic advantage for peritoneal cavity exposure to paclitaxel, compared with the systemic compartment, was observed. High levels of drug persisted within the cavity for longer than 48 hours following a single treatment. In addition, significant paclitaxel concentrations were found in the systemic compartment after i.p. treatment, despite the pharmacokinetic advantage demonstrated for cavity exposure. Several patients exhibited clinical and laboratory evidence of an antitumor response. On the basis of these data, further exploration of a potential role for i.p. paclitaxel in the management of ovarian cancer appears justified. PMID- 7865437 TI - Taxol (paclitaxel): future directions. AB - Paclitaxel is the first of a new class of anticancer agents with a novel mechanism of action. Demonstration of the broad activity of this drug and its unusual effects has refocused attention on tubulin as a target for anticancer drug development. Studies are under way to identify the optimal paclitaxel dose and schedule of administration and the effective combination regimens, and to exploit the drug's radiosensitizing properties. Efforts to define pharmacodynamic relationships and clinical mechanisms of resistance and to assess other potential mechanisms for the drug's anticancer activity are also under way. In addition, other compounds that target the microtubule, some more soluble and some more potent, are in various stages of development. Phase III trials in patients with ovarian, breast, and lung cancer are continuing, and adjuvant breast cancer trials will begin soon. Such trials will establish whether paclitaxel increases the cure rate and/or survival in cancer patients. PMID- 7865438 TI - Clinical pharmacology and metabolism of Taxol (paclitaxel): update 1993. AB - Paclitaxel may be one of the most important anticancer agents to be developed over the past 2 decades. With its unique mechanism of action as an inducer of tubulin assembly, paclitaxel has demonstrated impressive antitumor activity in patients with breast, lung (both non-small cell and small cell), head and neck, and advanced and platinum-refractory ovarian carcinomas. Unfortunately, there has been a relative lack of pharmacologic data available for paclitaxel, compared with other agents in similar phases of development. This scarcity of data is due, in part, to the aqueous insolubility of paclitaxel and to difficulties in developing sensitive analytic assays to measure the full range of drug concentrations achieved in small animals, both of which have limited preclinical pharmacologic studies. This report reviews the pharmacology of paclitaxel as ascertained during early clinical trials. Although most early studies used prolonged intravenous administration schedules of the agent as both monotherapy and in chemotherapy combinations, more recent studies have evaluated shorter administration schedules. In addition, available information pertaining to the pharmacodynamic and metabolic profiles of paclitaxel are discussed. Such information may be useful in designing rational treatment regimens of paclitaxel as a single agent and in chemotherapy combinations, potentially resulting in the optimal utilization of this important agent in cancer chemotherapeutics. PMID- 7865439 TI - Taxol (paclitaxel): a novel advance in chemotherapy. PMID- 7865440 TI - 19th Congress of the European Society for Medical Oncology. Lisbon, Portugal, November 18-22, 1994. Abstracts. PMID- 7865441 TI - Irradiated homologous aorta in eyelid reconstruction. Part II. Human data. AB - Reconstruction of posterior lamellar eyelid defects requires a tissue substitute that is either identical to the tissue lost (i.e., surrounding or nearby tarsus) or donor tissue that serves the same supportive role. With extensive lid defects, at times an alternative tissue to tarsus may be required. Irradiated homologous aorta is available as a posterior lamellar substitute. It provides a structural framework for the surrounding lid tissues to grow on and is incorporated into the normal eyelid anatomy. It is available to the reconstructive ophthalmic surgeons as an alternative donor tissue in the presence of extensive lid defects. PMID- 7865442 TI - Fused eyelids in premature infants. AB - The charts of 161 extremely premature newborns were reviewed to characterize and report the incidence of infants born with fused eyelids, to determine when postbirth eyelid dysjunction occurs, and to address the survivability of these infants. Logistic regression analysis was used to examine the relationship between various ophthalmic outcomes and possible predictors of these outcomes. For babies born with eyelids fused, Cox regression analysis was used to assess time to eyelid opening. From the analysis of our data, we found that the critical time for eyelid opening is between 25.5 and 26.5 weeks gestational age. If fused at birth, the average time to eyelid opening after birth was 5.5 days. Fifty-two percent of babies born with their eyelids fused survived to be discharged from the hospital, compared to 83% of those born with eyelids open. Gestational age was found to be the most important predictor of the status of the eyelids at birth, of survival, and of the presence of retinopathy of prematurity (ROP). Other variables were found to be significant, but the significance was lost once the variable was adjusted for gestational age. PMID- 7865443 TI - Changes in refraction and keratometry after surgery for acquired ptosis. AB - A retrospective study involving 47 lids in 26 patients was conducted to determine changes in refraction and keratometry after surgery for acquired ptosis. Refractive and keratometric data were obtained prior to and 6 months after levator surgery. Data were analyzed for changes in refractive sphere, cylinder, and cylindrical axis, as well as keratometry, toricity, and axis of toricity. Although patients noted subjective change in vision postoperatively and demonstrated changes in their refractive error, the changes were statistically insignificant. Consistency was noted; the cylindrical axis and the axis of toricity remained relatively stable after surgery. PMID- 7865444 TI - Another look at pterygium surgery with postoperative beta radiation. AB - Although complications associated with the use of beta radiation after pterygium surgery can occur, the author has found the use of beta radiation to be beneficial in preventing recurrences when used with pterygium surgery. An effective surgical regime of pterygium surgery is presented. A procedure made up of steps that tend to prevent revascularization of the operative site after pterygium surgery will decrease the recurrence rate. The use of strontium 90 and the mechanism of action of beta ray therapy in treatment of the pterygium is discussed. Few complications have occurred in > 200 surgically treated cases of pterygium with postoperative beta radiation administered with a strontium 90 applicator. No cases of radiation cataract have been observed. PMID- 7865445 TI - Argon green laser photoepilation in the treatment of trachomatous trichiasis. AB - We describe the treatment of focal trachomatous trichiasis with argon green laser. We treated 70 eyelashes in 17 patients with 80% success and found this treatment modality convenient both for the patient and the practitioner. PMID- 7865446 TI - The effect of fluorescein volume on lacrimal outflow transit time. AB - The Jones primary dye test is a commonly used test of lacrimal outflow. Some clinicians, however, find it of limited practical significance because of variable outcome and relatively low sensitivity in documenting normal lacrimal excretory function. We hypothesized that an important variable affecting the transit time may be the volume of fluorescein used in the primary dye test. To accurately determine the exact time from insertion of dye into the eye to its appearance in the nose, using a rigid nasal endoscope, we directly visualized the dye as it appeared at the ostium of the nasolacrimal duct. Fifty nasolacrimal outflow systems were examined in 25 normal volunteers. The fluorescein dye transit time was determined using a single drop of fluorescein on one side and multiple drops of fluorescein on the other side. Using a single drop of fluorescein, the median dye transit time was 8 min, compared to 1.4 min using multiple drops. These results suggest that the volume of fluorescein used may be an important factor affecting variability in the outcome of the primary dye test. PMID- 7865447 TI - Bilateral nasolacrimal duct obstruction associated with Crohn's disease successfully treated with dacryocystorhinostomy. AB - A 41-year-old woman developed epiphora due to bilateral nasolacrimal duct obstruction 1 year after a definitive diagnosis of Crohn's disease. Treatment with systemic and topical antibiotic therapy resulted in resolution of the left sided obstruction but epiphora persisted on the right side. The patient underwent standard dacryocystorhinostomy with insertion of silicone tubes. Six months after surgery, she remains free of symptoms. To our knowledge, this is the first report of bilateral nasolacrimal duct obstruction that occurred in a patient with active Crohn's disease. PMID- 7865448 TI - Systematized epidermal nevi: case report and review of clinical manifestations. AB - A 19-year-old woman developed papillary and pigmentary changes of the skin over her entire body with extensive eyelid involvement causing trichiasis. A four-lid blepharoplasty with rotation of the anterior lid lamella led to resolution of the ocular symptoms and secondary cosmetic improvement. Histologic examination of the tissue demonstrated epidermal nevi which are congenital abnormalities of surface or adnexal epithelium. This patient was diagnosed with systematized epidermal nevus as described by Lever's classification. There is a high association of epidermal nevi with other systemic abnormalities; that association is known as "epidermal nevus syndrome" (ENS). PMID- 7865449 TI - Hydroxyapatite orbital implant abscess: histopathologic correlation of an infected implant following evisceration. AB - A 60-year-old diabetic man with a history of ocular trauma and absolute glaucoma underwent evisceration with placement of an 18 mm hydroxyapatite orbital implant. The host scleral shell was left intact with no posterior opening for vascular ingrowth. One year later the patient presented with implant exposure, limited fibrovascular ingrowth into the implant, and a Staphylococcus aureus orbital abscess. The implant was removed, and pathology demonstrated suppurative inflammation with limited vascular ingrowth. This patient's risk factors for an implant-associated wound infection included diabetes, impaired wound healing, history of trauma, early implant exposure, and delayed fibrovascular ingrowth. Awareness of the infectious complications of any orbital implant including hydroxyapatite allows the surgeon to alter management strategies in an attempt to reduce such risk. Surgeons may consider posterior scleral portals with evisceration surgery to facilitate hydroxyapatite vascularization. Patient selection, implant size, and surgical technique are key factors for a management strategy designed to reduce the risk of implant infection. PMID- 7865450 TI - Progressive infraorbital nerve hypesthesia as a primary indication for blow-out fracture repair. AB - Traumatic blow-out fractures of the orbital floor are a common injury that can lead to significant morbidity. Accepted indications for surgical repair include displaced fractures consisting of a defect > 50% of the orbital floor, extraocular muscle entrapment, and clinically significant enophthalmos. Although infraorbital nerve hypesthesia has been reported as an indication for repair of fractures of the zygomatic complex and is often encountered as an associated finding in fractures of both the orbital floor and inferior orbital rim, it has not been generally regarded as a primary indication for blow-out fracture repair. We report two patients in whom severe, progressive infraorbital nerve hypesthesia served as the primary indication for surgical repair. Both patients experienced improvement in infraorbital nerve function following surgical repair, accompanied by persistent pain and paresthesias in the distribution of the infraorbital nerve. We suggest that progressive infraorbital nerve hypesthesia should be considered a primary indication for blow-out fracture repair in selected patients in whom hypesthesia is both severe and progressive. PMID- 7865451 TI - Exophthalmos and iatrogenic Cushing's syndrome. AB - A 38-year-old physician presented with a 9-month history of progressive self administration of oral prednisone < or = 160 mg per day for Addison's disease. Examination demonstrated typical Cushingoid features and bilateral proptosis with elevated intraocular pressure. Computed tomography disclosed increased intraorbital adipose tissue. We hypothesize that the increased intraorbital adipose deposition was due to the differential binding of glucocorticoids to adipose tissue receptors and an enhancement of lipoprotein lipase activity. We conclude that the findings in this case may be related to glucocorticoid-induced changes in the ocular and periorbital structures. Cushing's syndrome should be considered in the differential diagnosis of acquired exophthalmos and elevated intraocular pressure and findings of increased orbital fat on orbital imaging. PMID- 7865452 TI - Rhabdomyosarcoma: invading the orbit in an adult. AB - Sites in the head and neck region are among the most frequent locations of rhabdomyosarcoma (RMS) in patients younger than 15 years. However, comparable neoplasms in adults are very uncommon. We present a case report of a 27-year-old man who was diagnosed as having RMS. RMS rarely presents in the head and neck of adults, but should be considered in the differential diagnosis of a small cell neoplasm in patients during the third and fourth decades of life. PMID- 7865453 TI - Atypical periorbital xanthogranulomas associated with systemic benign lymphoepithelial lesions. AB - The report reviews the clinical, laboratory, and pathologic features of a 47-year old woman with systemic benign lymphoepithelial lesions in whom atypical periorbital xanthogranulomas with rare central necrosis subsequently developed. PMID- 7865454 TI - Periorbital dirofilariasis. AB - A differential diagnosis of inflammatory periocular soft tissue masses includes sarcoidosis, ruptured dermoid cyst, infectious abscess, metastatic neoplastic disease, and idiopathic pseudotumor. The authors present the case of a 42-year old woman with a periocular inflammatory mass caused by dirofilaria of a nematode classification as Dirofilaria tenuis. The extraction of the worm was curative and the patient has been symptom-free for the ensuing 12 months. This zoonotic infection, spread by mosquito vectors from animal hosts to humans, is rarely encountered in the United States as a cause of periorbital inflammation. A history of migratory swelling and residence in, or travel to, endemic areas (the southeastern United States) should suggest the possibility of Dirofilaria infection. PMID- 7865455 TI - Blood loss following chalazion excision. PMID- 7865456 TI - Transgenic mice expressing constitutive levels of IL-2 in islet beta cells develop diabetes. AB - IL-2 plays an important role in the clonal expansion of T cells during an immune response and it has been implicated in autoimmune disease. To examine the role of IL-2 in the regulation of peripheral tolerance we produced transgenic mice in which the expression of murine IL-2 was directed by the rat insulin II promoter. The IL-2 transgene was expressed specifically in the pancreas. Islets from transgenic mice synthesized biologically active IL-2. Expression of IL-2 in the pancreas resulted in a massive inflammatory response directed at the beta cells of the pancreas. The infiltrate consisted primarily of B cells and CD4+ and CD8+ T cells. The infiltrate resulted in destruction of the insulin-producing beta cells and diabetes, but there was no evidence for antigen specificity. The results suggest that local IL-2 production elicits the recruitment and activation of cells capable of destroying beta cells by non-antigen-specific mechanisms. PMID- 7865457 TI - Self-peptides bound to the type I diabetes associated class II MHC molecules HLA DQ1 and HLA-DQ8. AB - Genetic susceptibility to several autoimmune disorders is associated with the expression of certain MHC class II alleles. Insight into the etiology of such diseases awaits the identification of the class II restriction elements and the possible pathogenic peptides. Towards these aims, self-peptides bound to HLA-DQ1 and HLA-DQ8, allotypes considered to be neutral and permissive respectively towards the development of insulin-dependent diabetes mellitus, are reported. These naturally processed peptides were isolated from immunoaffinity purified HLA DQ molecules expressed in cultured B lymphocytes. The chromatographic profiles of the peptide repertoires are unique, whereas the size distributions exhibit general similarity to those reported for naturally processed self-peptides bound to HLA-DR. Twenty-eight individual peptides representing 10 nested sets were identified by combined Edman microsequencing and mass spectrometry. Peptide length varied from 13 to 74 amino acids. Source proteins included MHC molecules and other integral membrane proteins, as well as secretory, cytosolic and mitochondrial proteins. Promiscuous invariant chain peptides were identified among the self-peptides bound to HLA-DQ8. No dominant amino acid markers suggestive of particular enzymatic processing events were detected. Some structural features of DQ1 and DQ8 that may relate to the bound peptides are discussed. Peptide specificity was confirmed in binding assays with purified HLA DQ and HLA-DR protein. PMID- 7865458 TI - Analysis of natural and disease-associated autoantibody repertoires: anti endothelial cell IgG autoantibody activity in the serum of healthy individuals and patients with systemic lupus erythematosus. AB - The present study demonstrates that natural IgG with anti-endothelial cell activity is present in the serum of healthy individuals and in pooled normal human Ig. By using a novel method that allows for the simultaneous and quantitative assessment of reactivities of antibodies with a large number of antigens in tissues, we observed that natural anti-endothelial cell antibody (AECA) recognizes a restricted set of self antigens in endothelial cells that is conserved among healthy individuals. The extent to which natural AECA activity is expressed in serum and the pattern of reactivity of AECA with endothelial cell antigens showed little variability between individuals. Analysis of AECA in the serum of patients with systemic lupus erythematosus (SLE) revealed a higher amount of activity and a wider spectrum of antigenic specificities than that recognized by natural antibodies in endothelial cell extracts. AECA activity of IgG in whole serum was lower than that of purified IgG in the case of healthy individuals and showed little variation among individuals. In contrast, no difference was found between AECA activity of purified IgG and that of IgG in patients' serum suggesting that SLE sera lack the factors that control expression of AECA activity in the serum of healthy individuals. Our results indicate that natural autoantibodies recognize a restricted and conserved set of self antigens. Our observations further suggest that defective regulation of the expressed autoreactive B cell repertoire is the basis for expansion of novel clonal specificities and enhanced autoantibody activity in serum of patients with autoimmune disease. PMID- 7865459 TI - Complete genomic sequence and patterns of transcription of a member of an unusual family of closely related, chromosomally dispersed Ig gene clusters in Raja. AB - Ig genes in cartilaginous fish are organized in clusters. This unique form of organization suggests major differences in the regulation of the segmental rearrangement mechanism from that found in mammals and other higher vertebrates. The complete DNA sequence of an IgX-type cluster in the species Raja eglanteria is defined, and shown to consist of four rearranging segmental elements and three constant region exons. Using fluorescence in situ hybridization it is shown that Raja clusters are present at multiple sites within the genome, and that there is no apparent relationship between the chromosomally dispersed IgX clusters and a second isotype (IgM type) in this species. Comprehensive examination of sequence motifs associated with transcription regulation reveals an abundance of short sequences closely resembling those found in higher vertebrate Ig and other genes. However, the linear relationship of these motifs differs markedly from that associated with regulation of expression of the mammalian Ig gene locus. Additional studies of the transcription products of the IgX gene loci emphasize the diversity of transcription and processing of these genes. Considerable variation was noted in the processing of putative IgX transcripts, including the detection of a heretofore unrecognized form containing at least four additional Ig-like domains. These results have profound significance in terms of understanding the selective expression and the evolutionary diversification of Ig genes. PMID- 7865460 TI - Different cytoplasmic structure of the CD3 zeta family dimer modulates the activation signal and function of T cells. AB - The TCR complex transduces the antigen recognition signal through common activation motifs present in both CD3 gamma delta epsilon chains and zeta dimers within the complex. We have investigated functional roles of the cytoplasmic domain in zeta and CD3 gamma delta epsilon for T cell activation in early and late responses by comparing the signaling capability of the TCR complexes containing mutant zeta lacking some or all motifs, or eta chain, another zeta family molecule. The results with the mutant zeta lacking all motifs indicated that CD3 gamma delta epsilon can transduce signals to cause early activation events and production of IL-2 upon antigen stimulation in the absence of zeta motifs. However, any one of the zeta motifs was required to respond to Thy-1 stimulation and this requirement cannot be replaced by other CD3 chains. Such zeta motif-dependent responses were also observed in tyrosine phosphorylation of a 90 kDa protein upon TCR stimulation. Furthermore, we found that the C-terminal unique region of the eta chain exhibits inhibitory function in phosphorylation and Ca2+ response upon TCR stimulation as well as IL-2 production upon Thy-1 stimulation. Collectively, the present analyses suggest that two types of signals are induced through the TCR-CD3 complex: (i) the common motif-dependent signals which are mediated equally through zeta dimers and CD3 gamma delta epsilon, and (ii) zeta specific motif-dependent signals. Differences in the cytoplasmic domain of zeta family molecules may modulate the cooperation of these two signals, resulting in alteration of T cell functions. PMID- 7865461 TI - More efficient positive selection of thymocytes in mice lacking terminal deoxynucleotidyl transferase. AB - Mice with a drastic mutation in the terminal deoxynucleotidyl transferase (TdT) gene have recently been engineered. Igs and TCRs in these mice are essentially devoid of N-region diversity. Here we report that TdT0 mice contain elevated numbers of CD3hi single-positive (SP) thymocytes because more thymocytes make the transition from the immature double-positive to the mature SP stage. This suggests that the repertoire of TCRs encoded in the germline may be enriched for specificities capable of interacting with MHC molecules and that the loss of some of this affinity is the price paid for TdT-generated diversity. PMID- 7865462 TI - Lymph node homing cells biologically enriched for gamma delta T cells express multiple genes from the T19 repertoire. AB - Sheep gamma delta T cells have been shown serologically to express T19, a membrane protein of 180-200 kDa which is a member of the scavenger receptor superfamily. Previous work from this laboratory resulted in the detection of a multigene family of T19-like genes in the sheep genome. In this study nucleotide sequences from several T19 genes were determined and are reported along with the corresponding segments of a number of expressed mRNA molecules. A segment of a single sheep T19-like gene was sequenced and these data, along with the corresponding sequences from cloned T19-like cDNA molecules from sheep and cow, were used to design an oligonucleotide primer system suitable for amplification of corresponding segments of many T19 genes and their cDNAs. Between 30 and 40% of cloned T19 genes were amenable to amplification using the selected primers, and sequence analysis of cloned PCR products confirmed that different T19 genes encode unique amino acid sequences. The expression of multiple T19 genes was established using cDNA molecules obtained from a single sample of sheep lymphocyte mRNA. The possible role of the T19 family of genes is discussed. PMID- 7865463 TI - Definition of TCR recognition sites on Ld-tum- complexes. AB - The P911 variant of the P815 mastocytoma was shown by Lurquin et al. (Cell 58:293, 1989) to elicit rapid tumor rejection in a syngeneic host. This rejection was mediated by Ld-restricted cytotoxic T lymphocytes (CTL) for which targets could be sensitized by the synthetic peptide designated tum- (P91A-.12-24). In a previous study, T cell clones specific for Ld-tum- complexes displayed very restricted TCR usage and a characteristic TCR motif in the V alpha CDR3 region, predicted to interact with peptide. However, in contrast to the majority of Ld peptide ligands that are nonamers, the tum- peptide is a 13-mer and its sequence does not fit the Ld binding motif. Thus, to define shorter versions of the tum- 13-mer and residues involved in TCR recognition, nonamer derivatives were synthesized and compared in several different binding and functional assays. From these comparisons, the peptide TQNHRALDL was found to be the optimal nonamer. CTL recognition of Ala-substituted analogues of this peptide indicated that the His and Arg residues at positions 4 and 5 are important for TCR contact. We propose that these basic residues of the tum- peptide interact with the previously defined acidic residues in the CDR3 region of several TCR known to recognize Ld tum- complexes. PMID- 7865464 TI - Preferential utilization of the immature JH segment and absence of somatic mutation in the CDR3 junction of the Ig H chain gene in three X-linked severe combined immunodeficiency patients. AB - Human severe combined immunodeficiency (SCID) includes an X-linked SCID (XSCID) characterized by a complete absence of mature T cells, hypogammaglobulinemia and a normal or elevated number of B cells. XSCID results from mutation in the IL-2 receptor (IL-2R) gamma chain gene, which is thought to be involved in not only IL 2R but also IL-4R and IL-7R mediated signals. To investigate the VDJ recombination and Ig repertoire development in the absence of the IL-2R gamma chain, we intended to study the CDR3 junction in peripheral blood B cells of three XSCID patients. A total of 101 different CDR3 junctions were cloned following polymerase chain reaction amplification of polyclonal peripheral blood lymphocyte DNA. Sequence analysis of CDR3 junctions revealed that the primary antibody repertoire of the Ig H chain gene was assembled in a normal fashion. Among the JH segments, overexpression of JH3 segments was significant in XSCID patients compared with age-matched controls. D segment usage in XSCID was very similar to that in age-matched controls. All of the XSCID JH regions except for two clones were equal to germline JH genes, showing little or no evidence of somatic mutation. The results indicate that the immature JH segment is preferentially utilized and somatic mutation is absent in the CDR3 junction of the Ig H chain gene of XSCID patients. PMID- 7865465 TI - Human alpha beta and gamma delta T cells from unexposed individuals respond to protein antigens of the yeast form of Paracoccidioides brasiliensis. AB - Paracoccidioides brasiliensis, a dimorphic fungus, causes chronic granulomatous mycosis in susceptible individuals. Different reports have shown that cell mediated immunity is essential for protection against systemic mycosis, including paracoccidioidomycosis. We analyzed the reactivity of alpha beta and gamma delta T cells from unexposed Caucasian donors to P. brasiliensis yeast form components. Our results indicate: (i) alpha beta and gamma delta T cells proliferate after in vitro stimulation with lysates of P. brasiliensis; (ii) similar numbers of alpha beta T cells (f = 1/21,000) and of gamma delta T cells (f = 1/8000) respond to P. brasiliensis; (iii) P. brasiliensis-reactive gamma delta T cells express the V gamma 9V delta 2 TCR; (iv) the stimulatory activity of P. brasiliensis for both alpha beta and gamma delta T cells primarily resides in a high molecular weight (100 kDa) and in a low molecular weight (< 1 kDa) fraction; (v) the ligands responsible for stimulation of both alpha beta and gamma delta T cells are sensitive to proteinase treatment. We conclude that both alpha beta and gamma delta T cells from healthy individuals respond to ubiquitous protein antigens of P. brasiliensis. PMID- 7865466 TI - CD4+ T cell associated cytokine gene expression during experimental infection with Listeria monocytogenes: the mRNA phenotype of granuloma formation. AB - In murine listeriosis, elimination of bacteria and immunity to re-infection critically depend on Thy-1+CD4- cells, while cell-mediated inflammatory phenomena like delayed-type hypersensitivity and granuloma formation are mediated by CD4+ T cells. In an attempt to correlate T cell phenotype and function with a particular set of cytokines produced in vivo, we examined the cytokine gene expression profile associated with the presence or absence of CD4+ and/or CD8+ cells in the livers of mice during experimental infection with Listeria monocytogenes. T cell subset depletion was achieved by i.p. administration of saturating amounts of the appropriate mAbs, and mRNA detection was carried out using a qualitative and semi quantitative polymerase chain reaction-based mRNA amplification protocol. In both primary and secondary infection, the presence of CD4+ cells was a prerequisite for granuloma formation, and was found to be closely associated with mRNA expression for IL-2, IL-3 and IL-4, a 5-fold increase in expression of tumor necrosis factor (TNF)-alpha and granulocyte macrophage colony stimulating factor, and a 25-fold increase in expression of IFN-gamma and TNF-beta mRNAs, suggesting a role for these cytokines in granuloma formation. In striking contrast, depletion of CD8+ cells did not result in reduced mRNA expression for any one of the cytokines studied, implying that CD8+ T cell mediated cure and prevention of listeriosis may operate via qualitatively distinct mechanisms. PMID- 7865467 TI - Human immune response to HIV-1-Nef. I. CD45RO- T lymphocytes of non-infected donors contain cytotoxic T lymphocyte precursors at high frequency. AB - The immune response of peripheral blood lymphocytes (PBL) of non-exposed human individuals to the Nef protein of HIV-1 was studied. Nef is a regulatory protein of HIV which is immediately expressed after infection and which seems to be important in the pathogenicity of HIV. Nef may therefore serve as a potential target for effective immunity against HIV infection. Epstein-Barr (EBV) transformed lymphoblastoid B cell lines (LCL) were established from four healthy young seronegative adults and transfected with the Nef gene. These cells served as stimulator cells for autologous PBL in vitro and as target cells for CTL. CTL responses were readily generated against Nef-transfected LCL, consisting of Nef specific and putative EBV-specific CTL. Nef-specific CTL were generated exclusively from CD8+ cells and were MHC class I restricted. Since a vigorous Nef specific CTL response in non-infected individuals was unexpected, CTL precursor frequencies were determined by limiting dilution analyses in non-fractionated PBL and in PBL separated into the CD45RO- (naive) and CD45RO+ (memory) T cell populations. As expected, the putative EBV-specific CTL precursors were predominantly found in the CD45RO+ subset at frequencies typical for memory T cells. Nef-specific CTL precursors, in contrast, were found predominantly in the CD45RO- population, at even higher frequencies of approximately 1/1000-1/3000. Nef may thus display either an unusually high number of immunogenic peptides or a limited number of peptides presented in a very efficient way, so that many T cells including low affinity cells, would be triggered. PMID- 7865468 TI - Primary cytotoxic T lymphocyte induction using peptide-stripped autologous cells. AB - MHC class I molecules bind short peptides derived from endogenously synthesized proteins. This binding occurs at neutral pH and MHC class I-peptide complexes dissociate at low or high pH. Here we show that MHC class I-peptide complexes expressed at the cell surface dissociate upon a brief and mild acid treatment without affecting cell viability or capacity of the peptide-stripped MHC molecules to re-bind exogenous peptides. Mouse or human blasts that have been peptide-stripped and reloaded with an exogenous peptide can induce in vitro peptide specific primary cytotoxic T lymphocytes (CTL) in mixed lymphocyte cultures. Mice immunized with syngeneic blasts that have been peptide-stripped and reloaded with a peptide derived from a tumor-associated antigen are protected against a subsequent challenge with a lethal dose of tumor cells. The importance of these findings for viral and tumor immunotherapy as well as for unravelling the mechanisms of induction of primary CTL responses are discussed. PMID- 7865469 TI - The MHC class I-restricted T cell response to Sendai virus infection in C57BL/6 mice: a single immunodominant epitope elicits an extremely diverse repertoire of T cells. AB - We have used Sendai virus infection of C57BL/6 mice as a model with which to study the T cell response to a single MHC class I epitope. Cells taken from the bronchoalveolar lavage or restimulated in vitro from the mediastinal lymph nodes of virus-infected mice were strongly cytotoxic for a single nucleoprotein epitope, NP324-332/Kb. To correlate TCR usage with specificity for the immunodominant epitope, we generated T cell hybridomas from the bronchoalveolar lavage and mediastinal lymph node cells of C57BL/6 mice at the peak of infection. Altogether, 20 hybridomas were identified that specifically secreted IL-2 in response to NP324-332-pulsed L929-Kb cells. TCR usage in this panel of hybridomas was extremely diverse. Over half of the available J beta and V beta elements present in the C57BL/6 strain of mouse were represented in the hybridomas. Similarly, V alpha usage was also diverse and all 12 of the alpha chains sequenced used distinct J alpha elements. The only relatively conserved feature of the TCR in these hybridomas was the presence of an arginine residue in the junctions of 70% of the beta chains. These data demonstrate that a diverse repertoire of TCR is able to recognize a single MHC class I epitope. Moreover, the data demonstrate that mice make use of this potential diversity in the primary response to a natural viral infection. PMID- 7865471 TI - Biased TCR gene usage in alloreactive T cells specific for a structurally dissimilar MHC alloantigen. AB - Two models of allorecognition of MHC molecules have been proposed. One emphasizes specificity for MHC molecule-bound peptides and the other for exposed MHC polymorphisms. We predicted that the latter model would predominate in responder:stimulator combinations whose MHC molecules differed extensively in their TCR-contacting surfaces and that this would be reflected in biased TCR usage. Two panels of anti-DR11 T cell clones were generated, one from a DR17 and the other from a DR15 responder. The TCR-contacting surfaces of DR17 and DR11 have multiple differences, and those of DR15 and DR11 are very similar. TCR analysis by polymerase chain reaction amplification and mAb staining revealed that five out of nine DR17 anti-DR11 clones used the V beta 13 and two the V beta 6, family. In contrast seven different V beta families were used by the eight DR15 anti-DR11 clones. A similar bias in TCR V beta usage was observed in the polyclonal DR17 and DR11 T cell lines from which the clones were derived, and in a second DR17 anti-DR11 line from a different individual. These results support the concept that specificity for the foreign MHC structure itself may play an important role in the alloresponse between responders and stimulators with structurally dissimilar MHC molecules. PMID- 7865470 TI - Induction of ornithine decarboxylase activity in mouse B lymphocytes. AB - We have examined the role in B cell activation of ornithine decarboxylase (ODC), the labile rate-limiting enzyme in the synthesis of polyamines thought to be required for S phase entry in all cells. When small resting mouse splenic B cells were stimulated with the mitogenic agents phorbol myristate acetate (PMA) plus ionomycin (lo), LPS or the B cell specific agent F(ab')2 anti-lg, ODC activity was greatly increased. ODC activity in small dense B cells remained near baseline levels for the first 6 h after treatment with LPS, but then increased approximately 150-fold in the next 18 h. When purified B cells were not separated by cell density, ODC activity was 30-fold greater at baseline and rose earlier after LPS stimulation, reaching a level about three times that of LPS-stimulated small, dense B cells at 24 h, implying that large (preactivated) B cells have much greater ODC responses than small, dense B cells. ODC activity, like S phase entry, could also be induced in small, dense B cells by PMA and lo but failed to respond to either agent alone. ODC levels rose transiently by approximately 40 fold between 2 and 6 h following stimulation of small B cells with F(ab')2 anti lg, then declined to baseline. Whole anti-lg did not stimulate ODC activity and also blocked the F(ab')2 anti-lg mediated increase in ODC activity, just as it produced the expected inhibition of thymidine incorporation and cellular progression into S phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865472 TI - Type VII collagen DNA linkage analysis in a Japanese family with dominant dystrophic epidermolysis bullosa. AB - Type VII collagen, a major component of anchoring fibrils in the basement membrane zone, is now considered to be a primary genetic factor in the pathogenesis of dominant dystrophic epidermolysis bullosa (DDEB). In this study, we performed genetic linkage analysis in a Japanese family with DDEB using a PvuII polymorphism in the type VII collagen gene. The pedigree consisted of 10 affected and 13 unaffected living individuals and was diagnosed as having Cockayne-Touraine type of DDEB. Electron microscopic examination of the skin demonstrated a diminished number and rudimentary structure of anchoring fibrils. PCR-based detection of PvuII polymorphism resulted in 3 genotypes and co segregated with DDEB phenotype in this pedigree. The maximum lod score was 2.10 at recombination fraction (theta) of 0. The absence of recombination between DDEB and type VII collagen gene locus, as well as the observation of altered anchoring fibrils, suggested that type VII collagen is a candidate gene for the Japanese family with DDEB, although the lod score was statistically not significant. PMID- 7865473 TI - Dephosphorylation of the retinoblastoma gene product induced by differentiation and its relevancy to growth inhibition in normal human keratinocytes. AB - The retinoblastoma gene product (pRB) is a tumor suppressor gene product. Recently, it has been shown that the dephosphorylation of pRB leads a variety of cells into G1/G0 arrest. Keratinocytes were grown in serum-free MCDB 153 medium containing 0.1 mM Ca2+, followed by addition of Ca2+ to 1.8 mM (calcium switch). Under-phosphorylated pRB band appeared at 48 h and increased up to 72 h after calcium switch. S phase cells decreased at 48 and 72 h in a time-dependent manner. In contrast, the number of involucrin positive cells, differentiated cells, increased even at 24 h, preceding the dephosphorylation of pRB and continued to increase up to 72 h. These results indicate that the dephosphorylation of pRB is closely related to growth inhibition of human keratinocytes associated with differentiation. PMID- 7865474 TI - Effects of cytokines on the gamma interferon-induced tryptophanyl-tRNA synthetase expression by human keratinocytes. AB - Incubation of human keratinocytes with gamma interferon (gamma-IFN) has been shown to potently induce the synthesis of a 53 kDa protein which was recently identified as tryptophanyl-tRNA synthetase (TRS). However, in spite of the high sensitivity of cultured keratinocytes to TRS induction by gamma-IFN, the study of inflammatory skin lesions has allowed the detection of the protein only in a few cases, suggesting regulatory mechanisms from soluble endogenous mediators with antagonistic activity on the induction of TRS by gamma-IFN. Among these mediators, we wondered whether cytokines selected for possible anti-inflammatory activity and potentially derived from activated resident skin cells, such as IL 4, IL-10, TNF-alpha and TGF-beta, may be involved in the modulation of the keratinocyte TRS expression. To assess this possibility, we investigated the modulation of the synthesis of TRS by human cultured keratinocytes upon stimulation by various gamma-IFN/cytokine combinations. The effects were evaluated by immunoblotting assay revealed by enhanced chemiluminescence, with the aid of a specific antibody to the TRS protein. Results failed to demonstrate any effect of the tested cytokines, whether on the basal level of the TRS, or on the gamma-IFN-induced enzyme expression in keratinocytes. It is thus unlikely that such cytokines can account for the infrequency of the TRS detection in inflammatory skin processes. Further investigations of alternative working hypothesis should help elucidate the regulation of TRS in human keratinocytes. PMID- 7865475 TI - Time-dependent effect of chronic UV irradiation on superoxide dismutase and catalase activity in hairless mice skin. AB - Reactive oxygen species are produced by ultraviolet (UV) exposure and cause oxidative damage. Enzymic antioxidants such as superoxide dismutase (SOD) and catalase (CAT) may play important defensive roles in vivo. The previous studies have focused on the acute effects after single UV irradiation on those enzyme activities. In this study, we investigated the chronic effects of ultraviolet-A (UVA) or ultraviolet-B (UVB) exposure on the skin SOD and CAT activities using hairless mice. Accumulated doses of UVA and UVB after 36-week irradiation conducted 3 times a week were 3240 J/cm2 and 4320 mJ/cm2, respectively. SOD activity was increased by UVB irradiation and gradually returned to control levels, but was unaffected by UVA irradiation. In contrast, CAT activity was suppressed by UVA irradiation, indicating that the skin SOD and CAT activities are not coordinately regulated by long-term UV irradiation. These findings suggest that SOD activity is induced by repeated exposures to UVB in response to chronic photooxidative stress. However, continual cumulative stress may overwhelm the capacity of this system. These time-dependent changes of the cutaneous antioxidant system by chronic UV irradiation should provide us with important information on photooxidative events in cutaneous photoaging. PMID- 7865476 TI - Influence of alpha-melanocyte stimulating hormone on induction of contact hypersensitivity and tolerance. AB - Tumor necrosis factor-alpha (TNF-alpha) has been demonstrated to be the primary molecular mediator of impaired contact hypersensitivity induction after ultraviolet B radiation, but the mediator of ultraviolet B-induced tolerance remains obscure. Since alpha-melanocyte stimulating hormone (alpha-MSH) is generated within ultraviolet B-exposed skin, experiments were conducted to determine whether the cutaneous immune deficit caused by alpha-MSH is mediated by a TNF-alpha-dependent pathway, and/or whether alpha-MSH is responsible for UVB induced tolerance. When dinitrofluorobenzene was painted on alpha-MSH-treated skin of ultraviolet B-susceptible and ultraviolet B-resistant strains of mice, only weak contact hypersensitivity was induced. However, neutralizing anti-TNF alpha antibodies failed to restore contact hypersensitivity responsiveness to mice treated with alpha-MSH. Moreover, mice that first encountered hapten via alpha-MSH-treated skin failed to acquire tolerance; instead, these mice retained the ability to develop and display intense contact hypersensitivity when hapten was painted subsequently on normal (untreated) skin. We conclude that alpha-MSH can interfere with contact hypersensitivity induction, but cannot be considered a mediator of ultraviolet B-induced tolerance because skin treated with this neuropeptide does not support tolerance induction when hapten is applied epicutaneously. PMID- 7865477 TI - Autoantibodies to annexins: a diagnostic marker for cutaneous disorders? AB - Annexins/lipocortins are a group of structurally related calcium and lipid binding proteins which have been implicated as mediators of the anti-inflammatory action of corticosteroids. Autoantibodies against annexin-1 have been reported in association with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis and their presence has been hypothesized as the reason for the steroid resistance phenomenon. In this study we investigated IgG- and IgM autoantibodies against annexin-1,-2,-3,-4,-5 and -6 in sera of 221 patients with skin disorders and 114 healthy blood donors with newly established ELISAs. Patients were clustered into 5 groups according to their diagnosis: autoimmune diseases, psoriasis, leg ulcer, malignant melanoma, and miscellaneous diseases. Autoantibodies directed against each annexin were detectable in all investigated groups, in the control group as well as in the disease groups, without displaying any significant correlation to any of the disease states. The homogenous distribution of annexin-autoantibodies throughout the control group and all the disease groups studied, do not support the implication of annexin-autoantibodies in pathophysiological states and make them an unlikely candidate for use as a diagnostic marker. PMID- 7865478 TI - Disaccharide analysis of dermal fibroblast-derived glycosaminoglycans in the three-dimensional culture. AB - We performed the quantitative and qualitative analysis on the main disaccharide units of glycosaminoglycans produced by human dermal fibroblasts in the 3 dimensional culture supplemented with L-ascorbic acid 2-phosphate (Asc 2-p) comparing with the monolayer culture system. The addition of Asc 2-p rendered fibroblasts to the organization of the dermis-like 3-dimensional structure in vitro without any pre-treatments with the plastic dish. Main disaccharide units were analyzed using HPLC after 1-phenyl-3-methyl-5-pyrasolone (PMP) labeling. The addition of Asc 2-p significantly increased the total amount of main disaccharide units and, furthermore, the composition revealed it to be more similar to that of the dermis. This 3-dimensional culture may offer a simple and useful system to investigate the glycosaminoglycan metabolism of human dermal fibroblasts in vitro. PMID- 7865479 TI - An attempt to treat intractable skin ulcers with autologous dermal graft. AB - Five patients with a total of seven chronic intractable skin ulcers and impaired peripheral blood circulation were treated with autologous dermal grafts which did not contain any epidermal component. These ulcers were refractory to conventional therapy. Results from the dermal grafting were variable, with four of the ulcers (in two patients) healing 1-8 months after 1-5 graftings. These findings suggest the possibility that dermal grafting may be a simple yet effective treatment for deep, super-infected skin ulcers in which tendons and bones have become exposed. Dermal grafting may also provide an additional method by which to treat chronic skin ulcers which do not respond to conventional surgical therapy and where amputation of affected extremities is being considered. PMID- 7865480 TI - Epidermal turnover time. AB - Epidermal turnover time is the time taken for the epidermis to replace itself. The turnover time can be subdivided; when the epidermis is divided into proliferative compartment, differentiated compartment, and stratum corneum, the total turnover time is the sum of the turnover time of each compartment. Using Weinstein's data (J Invest Dermatol 82: 623-628, 1984), the epidermal turnover time was calculated to be 47-48 days instead of 39 days. PMID- 7865481 TI - Ultraviolet-B irradiation alters cytokine production by immune lymphocytes in herpes simplex virus-infected mice. AB - Previous studies from our laboratories have shown that UV-B irradiation at the site of an intradermal infection of herpes simplex virus (HSV) resulted in a higher incidence of zosteriform lesions and suppressed cellular immune responses to HSV in mice. In order to determine whether the production of T-cell-derived cytokine (IFN-gamma, IL-2 and IL-4) by immune cells from irradiated mice is also suppressed, we examined the production of cytokines by lymph node cells and spleen cells taken from UV-B irradiated, HSV type 1 (HSV-1)-infected mice. UV-B irradiation (120 mJ/cm2) prior to HSV-1 infection was found to markedly suppress IFN-gamma production compared to that of the non-irradiated control. IL-4 production was enhanced compared to IL-2 in the UV-B irradiated mice. These results suggest that alteration(s) in the cytokine production profile may therefore be involved in the development of severe skin lesions caused by HSV infection in UV-B irradiated mice. PMID- 7865482 TI - Interrelationship between ultraviolet light and recurrent herpes simplex infections in man. AB - In humans, epicutaneous application of a universally sensitizing dose (2000 micrograms) of dinitrochlorobenzene (DNCB) to skin exposed to 4 consecutive daily doses (144 mJ/cm2) of ultraviolet-B radiation (UVB) induces contact hypersensitivity (CH) in approximately 56% of normal, adult individuals (UVB resistant--UVB-R), but not in the remaining 44% (UVB-susceptible--UVB-S). In patients with biopsy proven basal/squamous cell cancer, the frequency of the UVB S trait exceeds 90%, indicating that this phenotype may be a risk factor for sunlight-induced skin cancer. Since many patients with recurrent herpes labialis complain that lip lesions are precipitated by acute sun exposure, we wondered whether the UVB-S trait might be associated with this recurrent disease. A group of 31 volunteers was selected, each with a history of numerous episodes of labialis secondary to reactivated herpes simplex virus-1 infection. Subjects were questioned carefully concerning factors, including sun exposure, thought to be important in precipitating lip lesions. Each individual was then subjected to the UVB plus DNCB protocol. When forearm skin of these individuals was assayed for CH after 30 days, 20 (65%) proved to be UVB-S (approximately 1.5 times the expected frequency), while the remainder displayed vigorous DNCB-specific CH. A strong history of sun-induced recurrent herpes simplex labialis did not predict the UVB phenotype. A subset of these subjects was exposed to 2 MEDs of UVB to their faces. None of the UVB-R subjects developed recurrent herpes labialis while 6 of 8 UVB-S subjects developed recurrent lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865483 TI - Effects of tretinoin tocoferil on gene expression of the extracellular matrix components in human dermal fibroblasts in vitro. AB - Recently, it has been reported that tretinoin tocoferil (TT), a synthesized ester bond compound of all-trans-retinoic acid and alpha-tocopherol, accelerates the formation of granuloma and is effective in promoting experimental open skin wound healing. To investigate whether TT affects the gene expression of extracellular matrix components of human dermal fibroblasts, we measured the mRNA levels of various extracellular matrix components of fibroblasts incubated with TT using specific cDNA probes. The mRNA levels of elastin increased up to 30% of the controls and those of collagen III and VI up to 60%. The mRNA levels of collagen I and fibronectin remarkably increased up to 90% of the controls. These results suggest that the stimulatory effect of TT on the gene expression of many extracellular matrix components might be one of the mechanisms of its promotion of wound healing. PMID- 7865484 TI - Effect of t-butylhydroperoxide on p-aminohippurat uptake in rabbit renal cortical slices. AB - OBJECTIVES: Oxygen free radical (superoxide radical, hydrogen peroxide, and hydroxyl radicals) have been considered to be responsible for the pathogenesis of ischemia reperfusion injury and toxic chemical injury in a variety of organs including myocardium, brain, intestine and kidneys. In in vitro models using a suspension of rat proximal tubule segments, t-butylhydroperoxide(t-BHP), a potent oxidant, induces the severity of tubular dysfunction as reflected by decreases in tubular respiration which is associated with a progressive increase in lipid peroxidation. The precise mechanism of t-BHP-induced cell injury remains to be determine. The study was carried out to determine the effect of oxygen free radicals on organic anion transport in renal proximal tubule. METHODS: By renal cortical slices, we studied accumulation of organic ions, PAH efflux oxygen consumption, lactate dehydrogenase (LDH), lipid peroxidation. The data are expressed as the mean +/- SE and evaluated for significance using Student's t test. A probability level of 0.05 was used to establish significance. RESULTS: Effect of t-butylhydroperioxide(t-BHP), a potent oxidant, on organic anion p amminohippurate(PAH) uptake was studied in rabbit renal cortical slices. t-BHP inhibited irreversibly PAH and organic cation tetraethylammonium(TEA) uptake in a dose dependent manner with IC50 of approximately 1.0 and 0.85 mM, respectively. The efflux rate constant pf PAH was not altered by the presence of 1 mM t-BHP, indicating that the inhibitory effect of t-BHP on the steady-state accumulation of PAH is due primary to the reduction in the influx of PAH across the basolateral membrane. The kinetic analysis showed that 1mM t-BHP caused a significant reduction in the maximum rate of PAH influx(Vmax) from 1.54 +/- 0.74 to 0.72 +/- 0.54 umol/g/10 min without an effect on Km, indicating that t-BHP depressed PAH influx across the basolateral membrane by reducing the number or turnover rate of active carrier for PAH transport, but not by altering substrate affinity of the carrier. Ouabain-sensitive and -insensitive oxygen consumption was not different between the control and t-BHP-treated slices. t-BHP caused an increase in LDH release and lipid peroxidation in a dose-dependent manner, which were highly correlated with changes in PAH uptake. CONCLUSION: These results suggest that t-BHP inhibition of PAH uptake is attributed to renal tubular cell damage and lipid peroxidation plays an important role in the inhibitory effect of t-BHP on PAH transport in rabbit proximl tubules. PMID- 7865485 TI - A case of coincident multiple myeloma and non-Hodgkin's lymphoma. AB - A rare case of coexisting multiple myeloma and non-Hodgkin's lymphoma at the time of diagnosis is presented. The patient presented with petechiae, melena and weight loss. IgA lambda monoclonal gammopathy in the serum and free lambda chain in urine were documented. Bone marrow biopsy demonstrated an interstitial infiltration of neoplastic plasma cells coexisting with localized collection of neoplastic lymphoid cells composed of monotonous small lymphocytes with occasional cleaved nuclei. Immunophenotype of plasma cell was IgA lambda. The patient also had a jejunal mass, with biopsy proven malignant lymphoma, diffuse small cleaved cell type. The tumor was diffusely positive for pan-B marker. After chemotherapy, the IgA lambda monoclonal protein decreased and the patient improved. This case suggest, that the seound B-cell neoplasm may have evolved by transformation of an original neoplastic clone, or that malignant tumors may be polyclonal at onset. Definitive diagnosis and staging of each disorder is important for proper management. PMID- 7865486 TI - Right atrial mass associated with hepatoma--2 case reports. AB - Hepatoma has a tendency to spread into the venous system, but intracavitary cardiac extension or metastasis of hepatocellular carcinoma is an uncommon form of cardiac malignancy. When the carcinoma grows from the hepatic vein into the right atrium, the right atrial tumor thrombis may hinder the blood flow. Therefore, these patients have the risk of sudden death. In the past, antemortem diagnosis of right atrial tumor thrombi in patients with primary hepatocellular carcinoma was difficult. But, echocardiography allowed easy detection of the intracardiac tumor thrombi. We describe two cases of hepatocellular carcinoma with right atrial tumor thrombi. In these cases, the right atrial tumor thrombi was detected by two-dimensional echocardiography. Recently, successful surgical removal of the right atrial tumor thrombi are reported in several cases. We advocate performing echocardiographic examination in patients with hepatoma who have cardiac symptoms and signs. PMID- 7865488 TI - A case of noncardiogenic pulmonary edema by ethanolamine oleate. AB - Endoscopic injection of sclerosing agents is a strategy for control of esophageal varix bleeding. Five percent solution of ethanolamine oleate(EO) has been used as sclerosing agent. It is well known that intravascular injection of oleic acid induces acute respiratory failure in animal models. However, EO-induced noncardiogenic pulmonary edema has not been reported in human. We report a case of noncardiogenic pulmonary edema developed after therapeutic trial of EO as sclerosing agent for esophageal varix. PMID- 7865487 TI - Acute herpetic esophagitis--a case report. AB - We report a case of acute herpetic esophagitis in a 33 year old man who was presumed to be immuno-compromised following prolonged steroid and cyclosporin treatment for acute rejection of a transplanted kidney. In Korea, all reported cases of herpetic esophagitis have been diagnosed in immuno-compromised and debilitated patients with a typical endoscopic appearance of ulcerating lesions. However, our patient showed multiple vesicular lesions without ulcer along the entire esophagus. The diagnosis was confirmed by colorimetric detection of herpes virus DNA using in situ hybridization. The endoscopic findings reported herein probably represent the typical early stage of acute herpetic esophagitis. PMID- 7865489 TI - Interphase cytogenetics of lung tumors using in situ hybridization: numerical aberrations. AB - OBJECTIVES: Since conventional cytogenetic analysis for bronchogenic carcinogenesis is limited by the difficulty to get enough number of high quality metaphase spreads, the development of new method to overcome above problems is strongly needed. Therefore, the introduction of non-radioactive in situ hybridization (ISH) with pericentromeric chromosome probes gave us the way to investigate the genetic events during carcinogenic process. We applied this method on lung cancer tissue to validate the possibility of this method for general usage and to analyze numerical chromosome aberration status and their clinical correlations. METHODS: A set of satellite DNA probes specific for chromosome 3, 7, 9, 11, and 17 was hybridized directly to paraffin-embedded tissue section of 30 non-small cell lung cancers. Mean chromosome index of each chromosome and frequency of polysomy for each chromosome were calculated. RESULTS: Mean chromosome indices for chromosome 3, 7, 9, 11, and 17 were 1.10, 1.13, 1.17, 1.12, and 1.17, respectively. Polysomy for a set of chromosomes was detected in all 30 cases except 4 cases which showed hypoploidy only for chromosome 3 or 7 in 2 cases and diploidy only for chromosome 3 or 11 in 2 cases. Among the set of chromosomes, mean chromosome index and polysomy frequency for chromosome 9 & 17 were significantly higher than that for others. Mean chromosome index or polysomy pattern for each chromosome was not much different among cell types or clinical stages. CONCLUSIONS: Our results show that chromosome ISH can be used to screen for numerical chromosome aberrations on paraffin tissue sections and further studies for ISH analysis with different probes on same tumor area or double-target ISH in large scale are needed to confirm above results and to elucidate the specific meanings. PMID- 7865490 TI - Universal emergence of precore mutant hepatitis B virus along with seroconversion to anti-HBe irrespective of subsequent activity of chronic hepatitis B. AB - OBJECTIVES: It has been controversial whether or not the emergence of precore mutant HBV is related to the severe form of chronic hepatitis B (CH-B). To further clarify the role of the precore mutant HBV in the natural course of CH-B, we conducted a longitudinal analysis of precore-region sequences according to the biochemical severity along with seroconversion to anti-HBe in patients with CH-B. METHODS: The precore sequences of the ten sets of serial serum samples, obtained from 6 chronic hepatitis B patients with (group I) and from 4 patients without subsequent biochemical remission after seroconversion to anti-HBe (group II), were analyzed by direct sequencing of DNA amplified by PCR. RESULTS: The precore mutant HBV having a G-A mutation at the nucleotide 1896 was most commonly found (9/10). Wild-type precore HBV was detected in 4 of 6 (66.7%) in group I and 3 of 4 (75.0%) in group II during HBeAg-positive period (p > 0.05), and during anti HBe-positive period it was found in 2 of 6 (33.3%) in group I and 0 of 4 (0%) in group II (p > 0.05). In contrast, precore mutant HBV was detected in 5 of 6 (83.3%) in group I and 2 of 4 (50.0%) in group II during HBeAg-positive period (p > 0.05), and in all patients of both groups during anti-HBe-positive period. CONCLUSION: The most common type of precore mutant HBV in Korea was the mutant with a G-A mutation at nucleotide 1896. The emergence of precore mutant HBV was a universal phenomenon during the natural history of CH-B; therefore, the precore mutant does not appear to have an pathogenic role in determining the severity of the CH-B. PMID- 7865491 TI - Effects of long-term treatment of captopril and enalapril on rat intestinal angiotensin converting enzyme specific activities. AB - OBJECTIVES: Angiotensin converting enzyme (ACE) has been shown to be an important peptidasse that play a role in digestion and assimilation of protein rich in proline such as casein, gliadin and collagen. Despite that ACE inhibitors have been popular for various types of hypertension and congestive heart failure, the effects of their long-term treatment on intestinal ACE activities are not known. Therefore, we measured intestinal specific activities in rats after four weeks' treatment of ACE inhibitors. METHODS: Thirty Wistar rats weighing about 200g in average were divided into three groups, and supplied with tap water, captopril solution and enalapril solution respectively for four weeks. After sacrificing, intestinal ACE specific activities were measured in homogenate and brush border membrane fraction respectively, which was prepared from three equally divided segments of removed small intestine. RESULTS: ACE specific activities of proximal, middle and distal segments of control group were 178.6 +/- 64.2, 180.3 +/- 60.2 and 48.6 +/- 13.1 in brush border membrane (mean +/- SD, nmol/min/mg protein) respectively. Those of captopril group were 314.2 +/- 72.5, 281.0 +/- 69.8 and 67.7 +/- 21.8 respectively, showing tendency of increase in proximal and middle segments (p < 0.01 and 0.05 respectively). By contrast, those of enalapril group were 48.5 +/- 27.6, 70.7 +/- 15.6 and 11.6 +/- 4.4 respectively, which were significantly lower (p < 0.01) than those of control group. CONCLUSION: Rat intestinal ACE specific activities were not inhibited by captopril treatment, but inhibited by enalapril treatment. This finding may explain why there has not been any case report of malabsorption in patients taking captopril. But the malabsorption of prolyl peptide could be possible in cases with long-term administration of enalapril. PMID- 7865492 TI - The effect of eradication of Helicobacter pylori upon the duodenal ulcer recurrence--a 24 month follow-up study. AB - OBJECTIVES: To evaluate the effect of eradication of Helicobacter pylori(H.pylori) in the patients with duodenal ulcer(Du) upon the DU recurrence. METHODS: This study was performed for 190 patients with DU. Four different methods-microscopy of Gram stained mucosal smear, specific culture, biopsy urease test, histology of H &E staining-were taken for identifying colonization of H. pylori before treatment, and for finding the eradication of H. pylori 4 weeks after completion of therapy in each treatment group (cometidine, omeprazole, colloidal bismuth subcitrate(CBS), CBS and metronidazole double therapy, CBS, metronidazole and amoxicillin triple therapy). To detect DU recurrence, the gastroscopy was performed at 6, 12, 18, and 24 months after therapy. RESULTS: The eradication rate of the cimetidine group the omeprazole group, and the CBS group were 0%, 7.7%, 0%, respectively, and that of the double therapy group and the triple therapy group were 44.4% and 89.3%, respectively. Seventy three patients who were followed up for 2 years were categorized into two groups according to the eradication of H. pylori. The recurrence rate was 3.2% both in 1 year and 2 years later in the former group-one consisting of 31 patients with H. pylori eradicated, while the recurrence rate was 57.1% in 1 year and 78.6% in 2 years later, in the latter group-the other of 42 patients with H. pylori not eradicated. CONCLUSION: The eradication of H. pylori in patients with DU reduces the recurrence of DU. PMID- 7865493 TI - A clinical consideration of systemic embolism complicated to infective endocarditis in Korea. AB - OBJECTIVES: Infective endocarditis is still one of the important fatal diseases in Korea, especially when systemic embolisms are supervene. So, identification of patients who are in the high risk of embolism and who can be helped by early surgical intervention is very important. Considering these, we tried to elaborate the risk factors for the systemic embolism in patients with an infective endocarditis and the influence of systemic embolism on the mortality and morbidity in patients with an infective endocarditis. METHODS: We retrospectively reviewed the clinical records of 97 patients who were admitted with the infective endocarditis between January 1983 and October 1993. RESULTS: Among 97 patients, 80 patients met our diagnostic criteria. The mean age of patients was 38 years old. There were 43 males and 37 females. The mean duration of fever since the fever developed by history was 38 days. Valvular heart disease was the most frequent underlying heart disease. Mitral regurgitation and aortic regurgitation were the most common among valvular heart diseases. Pneumonia and acute pharyngotonsillitis were the most frequent predisposing factors of infective endocarditis. Blood cultures were positive in 51 patients (63.8%). Streptococcus viridans was the organism isolated most frequently, and Staphylococcus aureus was the second most frequently isolated one. Vegetations were detected in 58 patients (76.3%) by an echocardiography. Mitral valve and aortic valve were the most frequently involved incidence rate of embolism was 50% and the most frequent embolism site was the central nervous system and extremities were the next. Embolism occurred at the mean of 37 days after onset of fever. Overall in hospital mortality rate was 26.3% and a cardiac-origin was the major cause of death. The only statistically significant risk factor for mortality was systemic embolism. The analysis of the relation between an incidence of embolism and the multivariables (age, presence of vegetation, location of vegetation, size of vegetation, causative organisms) showed that only the growth of Staphylococcus aureus had a significant trend toward a risk of subsequent systemic embolism. CONCLUSION: This study suggests that systemic emboli increases the mortality rate in patients with infective endocarditis. Age of patients, presence of vegetation, size and location of vegetation are not the risk factors for embolism, while certain organism, especially Staphylococcus aureus, could be a risk factor for the systemic embolism. PMID- 7865494 TI - The cytokines, interleukin-1 beta, interleukin-6 and interferon-gamma upregulate the expression of intercellular adhesion molecule-1(ICAM-1) in rat thyroid cell line, FRTL-5. AB - OBJECTIVES: Recently, the role of adhesion molecules in the immune system has been recognized. ICAM-1 plays an important role in a variety of inflammatory and immune mediated mechanisms, including recruitment and targeting of lymphocytes. We observed the effects of cytokines on expression of rat homologue of human intercellular adhesion molecule-1 in rat thyroid cell line, FRTL-5. METHODS: We have examined expression of rat intercellular adhesion molecule-1 (ICAM-1, CD54), a homologue of human intercellular adhesion molecule-1, by immunocytochemistry (immunoperoxidase staining) in the continuously growing rat thyroid cell line, FRTL-5. RESULTS: Low level of ICAM-1 expression was noted at basal condition and this basal expression was not influenced by thyrotropin. Expression in rat homologue of ICAM-1 is increased by interferon-gamma, interleukin-1 beta and interleukin-6 with a dose dependent manner. CONCLUSION: These results show that a pure line of rat thyroid cells can express an ICAM-1 homologue and this is directly enhanced by cytokines such as rat interferon-gamma, human interleukin-1 beta and interleukin-6. Expression of this homologue is partially responsible for lymphocyte adhesion to thyroid cells, which is likely to be a major event in T cell recognition of thyroid antigens in autoimmune thyroiditis. PMID- 7865495 TI - Impairement of endothelium-dependent relaxation in chronic two-kidney, one clip hypertensive rats. AB - OBJECTIVES: Hypertension is commonly associated with an endothelial dysfunction that may contribute to the rise in blood pressure. Little information has been available so far on the role of endothelium-derived nitric oxide(EDNO) in renin dependent, 2-kidney, 1 clip(2KIC) hypertension. The present study was aimed to determine a role for EDNO in the development and maintenance of 2KIC hypertension. METHODS: The effects of blocking synthesis or supplementation with precursor of EDNO on the development of hypertension were determined in 2KIC rats. Vascular responses to acetylcholine, nitroprusside, atrial natriuretic peptide and nifedipine were examined in 7- and 12-week hypertensive 2KIC rats. RESULTS: NG-nitro-L-arginine-methyl ester caused a sustained increase of blood pressure in normal rats, while it was only partially associated with a more pronounced increase of blood pressure in the developmental phase of hypertension in 2KIC rats. In 7-week and 12-week hypertensive rats, phenylephrine-induced contraction of the isolated thoracic aortic rings was more sensitive compared with control. Their acetylcholine-induced relaxation was attenuated while the responses to nitroprusside or atrial natriuretic peptide were unaltered. Although their blood pressure did not differ between 7-week and 12-week hypertensive groups, the attenuation in the acetylcholine-induced relaxation was more prominent in the latter with a longer duration of hypertension. Indomethacin did not affect the attenuated relaxation to acetylcholine. The relaxation response to nifedipine was more pronounced in 2KIC rats. CONCLUSION: These results indicate that ENDO has little influence of the 2KIC hypertension, at least during its developmental phase, which is associated with an activated reninangiotensin system. The chronic stage of 2KIC hypertension, however, is associated with an endothelial dysfunction which may contribute to the enhanced vasoconstriction and sustained high blood pressure. PMID- 7865496 TI - Serotonergic markers in platelets of patients with major depression: upregulation of 5-HT2 receptors. AB - The uptake of [3H]5-HT and the density (Bmax) as well as affinity (Kd) of 5-HT uptake sites labelled with [3H]paroxetine and of 5-HT2 receptors labelled by [3H]LSD were determined in platelets from 25 medication-free patients with major depression and 20 normal controls. The density (Bmax) of 5-HT2 receptors was found to be significantly increased (by 52%) in platelets from depressed patients, particularly females. No changes were found in the affinity (Kd) of 5 HT2 receptors and in 5-HT uptake or [3H]paroxetine binding parameters. Density of 5-HT2 receptors positively correlated with that of [3H]paroxetine sites in control but not in depressed subjects. No correlation was found between the HAMD scores and Bmax of [3H]LSD binding. The results suggest that upregulation of platelet 5-HT2 receptors is a useful biological marker in major depression, particularly in females. PMID- 7865497 TI - Association of NAG levels with specific psychiatric symptoms in unipolar patients. AB - The levels of N-acetyl-beta-glucosaminidase (NAG) from 57 unipolar patients were compared to the scores of symptom severity for nine symptom clusters derived from the Symptom Check List (SCL-90). The depression and hostility clusters were significantly associated with NAG levels. In a separate study of 21 unipolar patients, six out of 31 mood symptoms were significantly associated with NAG levels, as were two out of seven tested RDC depression subtypes. Serotonin abnormalities may play a role in the production of many of these symptoms. A hypothesis that NAG could be a marker for serotonin activity is discussed. PMID- 7865498 TI - Acute treatment with antidepressant drugs selectively increases the expression of c-fos in the rat brain. AB - Rats were treated acutely, ip, with saline vehicle or an antidepressant: iprindole (15 mg/kg), nortriptyline (15 mg/kg), A75200 (10 mg/kg), fluoxetine (15 mg/kg), desipramine (10 mg/kg), bupropion (20 mg/kg) or tranylcypromine (7.5 mg/kg). Mapping the neuroanatomical distribution at 64 sites of the immediate early gene, c-fos revealed several patterns: first, increased counts of Fos-like neurons were found in all but one instance; second, drugs which had dopaminergic effects (bupropion and tranylcypromine) were more likely to potentiate c-fos reactivity than were the other drugs; third, Fos-like counts were more likely to be significantly elevated in structures bordering brain ventricles; fourth, only in the central amygdala were the Fos-like counts higher in all seven drug groups relative to the saline group. It remains to be seen whether or not this shared substrate is therapeutically significant. PMID- 7865499 TI - The prevalence of cognitive distortion in depressed adolescents. AB - This study examined the prevalence of cognitive distortion in depressed adolescents. Ninety-four consecutive depressed adolescent psychiatric outpatients were administered the Beck Depression Inventory, the Dysfunctional Attitude Scale, the Interpersonal Dependency Inventory and the Maudsley Personality Inventory. Depressed patients who scored above a threshold for cognitive distortion were compared to those who fell below the threshold. Of the depressed patients, 47.4% were found to meet the severity criteria for cognitive distortion, while the remaining 52.6% were found to be below the severity threshold. Cognitive distortion was associated with more severe symptoms of depression, lack of social self confidence and greater introversion. These results do not support the hypothesis that cognitive distortion is universal in clinical depression. However, they do suggest that cognitive distortion is associated with more severe depression. PMID- 7865500 TI - Cholinergic neurotransmission seems not to be involved in depression but possibly in personality. AB - Concordant with the adrenergic-cholinergic imbalance hypothesis of affective psychosis, there is a cholinergic supersensitivity in depression. Thus, the anticholinergic properties of some antidepressants might contribute to their efficacy. However, in the present double-blind studies (n = 20) with mianserin and viloxazine, respectively, which lack anticholinergic properties, adjunctive treatment with the anticholinergic biperiden versus placebo did not enhance the antidepressive efficacy. Therefore, we hypothesized that cholinergic supersensitivity might be linked to some possibly predisposing dimension of personality. Indeed, in healthy male volunteers (n = 11) the behavioral and cardiovascular sensitivity to physostigmine correlated significantly with "irritability" and "emotional lability" as well as with habitually passive strategies in stress coping. The rise in plasma cortisol and norepinephrine correlated with "retardation"; that of epinephrine with active coping. Thus, the cholinergic supersensitivity in affective psychoses might be linked to a personality dimension like stress sensitivity rather than to the diagnostic category itself. PMID- 7865502 TI - [Seasonal depression and phototherapy: problems and hypotheses]. PMID- 7865503 TI - Antidepressant failure: augmentation or substitution? PMID- 7865504 TI - A simple test to monitor the motor dysfunction in a transgenic mouse model of amyotrophic lateral sclerosis. AB - We reported recently that transgenic mice overexpressing human neurofilament heavy (NF-H) proteins develop a progressive neurological disorder with pathological features resembling those found in amyotrophic lateral sclerosis (ALS) (Cote et al 1993). A simple behavioral test, the grasping ability, has been used here for evaluating the motor dysfunction during aging of NF-H transgenic mice. Transgenic mice overexpressing NF-H proteins are normal at birth but they progressively fail to uphold their weight when tested for their grasping ability. The deficits in motor function during aging correlate with a progressive disruption of peripheral nerve function as evidenced by the atrophy and degeneration of distal axons. PMID- 7865505 TI - Development of an intravenous membrane oxygenator: a new concept in mechanical support for the failing lung. AB - An intravenous membrane oxygenator is being developed to supplement oxygen and carbon dioxide exchange in patients with temporary and potentially reversible lung failure in either a lung transplantation setting or in cases of acute respiratory distress from multiple causes. Our device incorporates a pulsatile balloon that is centrally located and around which are mounted microporous hollow fibers. Oxygen is vaccuumed through the fibers with resultant gas exchange. The rhythmic pulsations of the balloon enhance cross-flow and three-dimensional convective mixing at the blood-fiber interface and thus promote more efficient oxygen-carbon dioxide exchange. Seven intravenous membrane oxygenator prototypes have been designed and fabricated. Modifications in design have led to a progressive improvement in gas flux. Gas exchange performance measured in vitro and with both saline solution and fresh ox blood have shown gas exchange as high as 203 ml/min/m2 for oxygen and 182 ml/min/m2 for carbon dioxide. In vivo dog experiments with the device positioned in the inferior vena cava and right atrium have shown over a 50% increase in oxygen flux with balloon activation versus the static situation without changes in hemodynamics. The size of the prototype tested in animals can be scaled up fivefold for anticipated human trials. Our results indicate that our intravenous membrane oxygenator prototypes now under development may be an alternative to extracorporeal membrane oxygenation in the treatment of temporary respiratory failure. PMID- 7865501 TI - [Relations between specific neurochemical systems and memory: problems posed by dementia of the Alzheimer type]. PMID- 7865506 TI - Methotrexate therapy in pediatric heart transplantation as treatment of recurrent mild to moderate acute cellular rejection. AB - We have used adjunctive therapy with methotrexate as treatment of recurrent mild to-moderate acute cellular rejection and in an attempt to reduce rejection frequency and corticosteroid dosage. The purpose of this study was to review our experience with this treatment strategy. Eight patients, 13.1 +/- 1.1 years of age (mean +/- standard error of the mean) at the time of transplantation, were given methotrexate in addition to their standard triple therapy immunosuppression. Methotrexate was started at 6.2 +/- 2 months after transplantation after an average of 3.1 +/- 0.4 rejection episodes. Patients were given methotrexate weekly for 8 weeks at 2.5 or 5 mg orally every 12 hours for three doses (0.23 +/- 0.02 mg/kg/week). The time to resolution of rejection was 17.9 +/- 4 days after initiating methotrexate therapy. The number of rejections per month decreased significantly from the 2 months before methotrexate therapy (1.49 +/- 0.1) when compared with both the 2 months during methotrexate therapy (0.50 +/- 0.1) and the 2 months after methotrexate therapy was completed (0.44 +/ 0.3) (p < 0.005). Furthermore, when comparing total rejection frequency since transplantation and before methotrexate therapy to a follow-up period of 21.8 +/- 5 months after completion of methotrexate therapy, the rejection frequency was significantly less (0.81 +/- 0.2 versus 0.10 +/- 0.06 rejections/month) (p < 0.01). Prednisone dosage was also significantly less when comparing the time before methotrexate therapy to immediately after completion of methotrexate therapy (0.23 +/- 0.04 versus 0.15 +/- 0.03 mg/kg/day) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865507 TI - Echocardiographic analysis of rejection in the infant heart transplant recipient. AB - Eleven children who received transplants at less than 2 years of age underwent 59 echocardiograms at the time of endomyocardial biopsy for the assessment of the ability of echocardiography to predict acute rejection in the infant heart transplant recipient. Two patients died of acute rejection and autopsy findings were compared with premortum echocardiograms. Biopsy specimens were graded as no rejection (n = 46), mild rejection (cellular infiltrate, n = 5), or moderate severe rejection (myocyte necrosis/edema, n = 8). Echocardiographic indexes measured included the following: left ventricular mass, left ventricular volume, ejection fraction, heart rate, and peak rate of posterior wall thinning. Compared with controls, patients during mild rejection had slower posterior wall diastolic thinning (p < 0.01). No significant change was noted in left ventricular mass until endomyocardial biopsy specimens showed severe rejection. No significant changes were noted in heart rate or ejection fraction in any of the groups. In conclusion, decrease in the peak rate of posterior wall diastolic thinning may be a sensitive indicator of acute rejection in the infant heart transplant recipient. PMID- 7865508 TI - T-cell lymphoma in a child after heart transplantation. AB - Lymphoproliferative disease remains a small but worrisome problem after organ transplantation. This disorder is often a B-cell proliferation associated with Epstein-Barr virus. This article describes the unusual association of Epstein Barr virus with a T-cell lymphoma in a child after heart transplantation and ultimately an atypical rejection episode with an increased number of eosinophils. PMID- 7865510 TI - Dobutamine stress echocardiography after heart transplantation. AB - Dobutamine stress echocardiography was performed in 28 heart transplant recipients to study its value in the detection and staging of transplant vasculopathy. Fourteen patients had angiographic evidence of coronary artery disease (group 1), and 14 had angiographically normal coronary arteries (group 2). The dobutamine stress protocol called for a dose increase of dobutamine every 3 minutes until the age-predicted maximal heart rate was achieved. In groups 1 and 2, the mean maximal dose of dobutamine was, respectively, 24 +/- 9 micrograms/kg min and 29 +/- 8 micrograms/kg min, and the mean rate-pressure product was, respectively, 12386 +/- 1777 mm Hg/min and 10753 +/- 1085 mm Hg/min at rest, increasing to 20987 +/- 4020 mm Hg/min and 19795 +/- 2728 mm Hg/min at maximal dose. No patient in group 1 or 2 had deterioration of global or regional wall motion under dobutamine stress. In group 1, seven patients had wall motion abnormalities at rest, normalizing in five of them under dobutamine stress. In group 2, four patients had wall motion abnormalities at rest, normalizing in all patients under dobutamine stress. Consequently, this protocol of dobutamine stress echocardiography is unsuitable for the early detection of transplant vasculopathy despite its proven value in the general population. Conversely, these data suggest that the functional sequelae of transplant vasculopathy are not necessarily prominent, despite the known angiographic underestimation of the extent of the disease. PMID- 7865509 TI - Noninvasive detection of transplant coronary artery disease by dobutamine stress echocardiography. AB - Coronary artery disease has emerged as the leading cause of late morbidity and mortality in heart transplant recipients. The incidence of allograft coronary artery disease has been reported to be as high as 40% to 50% by 5 years. Coronary angiography remains the standard approach for surveillance of coronary artery disease in this patient population. However, the detection and surveillance of allograft coronary disease by noninvasive methods remains a challenge. The purpose of this study was to determine the value of dobutamine stress echocardiography as a noninvasive screening test to rule out the presence of anatomically significant allograft coronary artery disease and to assess its prognostic power. Dobutamine stress echocardiography was carried out according to a standard protocol in which dobutamine was infused at 5, 10, 20, 30, and 40 micrograms/kg/min intravenously at 5-minute stages with 12-lead electrocardiogram and blood pressure monitoring. Left ventricular wall motion was analyzed at baseline and at peak dobutamine dose. Mean age (+/- standard error of the mean) of the study population was 50.5 +/- 1.5 years, and mean duration (+/- standard error of the mean) since transplantation was 57 +/- 5 months. The sensitivity, specificity, and positive and negative predictive accuracy of dobutamine stress echocardiography were 95%, 55%, 69%, and 92%, respectively. In the 12-month follow-up study 12 patients with abnormal dobutamine stress echocardiographic findings had 15 major cardiac events whereas no event occurred in patients with normal dobutamine stress echocardiograms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865511 TI - Prognostic significance of sustained ventricular tachyarrhythmia occurring during dobutamine infusion. AB - The prognostic significance of a de novo sustained ventricular tachyarrhythmia occurring during a dobutamine infusion is unknown. This study was performed to determine (1) the risk of recurrent ventricular arrhythmia, (2) the safety of future dobutamine infusions, and (3) the role of electrophysiologic testing. The study population consisted of 15 patients, six with coronary artery disease, and nine with idiopathic dilated cardiomyopathy. Mean ejection fraction was 17% +/- 4.1%. The arrhythmia during the infusion was ventricular tachycardia in 13 patients and ventricular fibrillation in two patients and was not associated with preceding hemodynamic instability, electrolyte abnormality, digoxin toxicity, or antiarrhythmic drug therapy. During electrophysiologic testing, 7 of 15 patients had inducible ventricular tachycardia. All patients with inducible ventricular tachycardia were treated with either antiarrhythmic drugs, defibrillators, or ablation. Over a 12.3 +/- 5.2 month follow-up period, all 15 patients received further dobutamine treatment. Seven of 15 (47%) had a recurrent sustained ventricular tachyarrhythmia. Although three of seven recurrences occurred during a dobutamine infusion, all three of these patients had hemodynamically unstable conditions and were receiving high-dose (> 10 micrograms/kg/min) therapy at the time of recurrence. The other four recurrent arrhythmias were not associated with clear precipitating factors. Ejection fraction, origin of left ventricular dysfunction, and inducibility at baseline electrophysiologic testing did not predict arrhythmia recurrence. The de novo occurrence of a sustained ventricular tachyarrhythmia during dobutamine infusion is associated with a significant risk of arrhythmia recurrence (47%), which can occur in the presence or absence of dobutamine therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865512 TI - Grade 2 cellular heart rejection: does it exist? AB - According to the International Society for Heart and Lung Transplantation, a single focus of lymphocytic infiltration associated with myocyte injury in a cardiac allograft endomyocardial biopsy is focal moderate cellular rejection (Grade 2). We reviewed 115 endomyocardial biopsy specimens that were completely negative (n = 17), had a Quilty A (n = 17) or Quilty B (n = 46) lesion, or had a lesion fulfilling the criteria of grade 2 rejection (n = 35). By studying step sections (mean = 18) or sections stained for elastic tissue and collagen, we showed continuity of the focus of grade 2 rejection with the endocardium in 32 of 35 cases; these results justify reclassification of these foci as Quilty B lesions, which are defined as endocardial infiltrates that encroach on the underlying myocardium and that may be associated with myocyte injury but are not generally considered to represent acute rejection. Immunohistochemical staining for T and B lymphocytes and histiocytes showed similar patterns in deeper zones of Quilty B lesions and lesions initially regarded as grade 2 rejection. Normal hemodynamics were observed with 16 of 17 completely negative biopsy specimens, 16 of 17 Quilty A biopsy specimens, 46 of 46 Quilty B biopsy specimens, and 35 of 35 grade 2 rejection biopsy specimens. No grade 2 rejection was treated; only 1 biopsy specimen progressed to grade 3A rejection in a subsequent biopsy 2 months later. Most, if not all, cases of grade 2 cellular rejection can be shown to be Quilty B lesions, are not associated with hemodynamic abnormalities, and do not require augmented immunosuppression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865513 TI - Cytotoxic T lymphocytes infiltrating the human cardiac allograft show a restriction in T-cell receptor V beta gene usage: a study on serial biopsy and blood specimens. AB - T lymphocytes were propagated in vitro from endomyocardial biopsy specimens that were obtained weekly from four patients during the first 2 to 3 months after heart transplantation. The culture was performed in the presence of recombinant interleukin-2 and interleukin-4, with or without mitogen, in which especially CD8+ donor-specific cytotoxic T cells expanded. These cells, presumably reflecting an in vivo activated population, could even be cultured from biopsy specimens without histopathologic signs of rejection. A preferential expression of T cell receptor V beta gene families was found in these T-cell lines. This finding is in contrast with the heterogenous expression in peripheral blood T cells of the same patient. The restriction in V beta gene family expression was substantiated in the evaluation of clones obtained from two cell lines. Among 17 donor-specific cytotoxic T-cell clones derived from one cell line, only four V beta gene families were expressed. All five clones from the other cell line used the V beta 8 family. Some clones expressing a distinct V beta gene family used the same V-D-J junction sequence, indicative of their origin from the same precursor. With the use of oligonucleotide probes complementary to clone-specific V-D-J junction sequences, four of five clones were detected not only in the parent T-cell line but also in T-cell lines derived from biopsy specimens with rejection reactions taken 1 week earlier and 2 weeks later and in blood cells taken before and 0.5, 3, and 6 months after transplantation; these clones were not detected in blood cells harvested 12 months after transplantation. This study showed a restricted usage of the V beta gene families by activated donor-specific cytotoxic T lymphocytes in the heart transplant. PMID- 7865514 TI - Histologic and molecular diagnosis of myocardial human cytomegalovirus infection after heart transplantation. AB - A total of 879 paraffin-embedded endomyocardial biopsy specimens from 69 heart transplant recipients were studied. In 30 biopsy specimens, the presence of human cytomegalovirus was investigated by routine histologic and immunohistochemical evaluation, in situ hybridization, and polymerase chain reaction. These 30 biopsies were performed in seven patients with clinical human cytomegalovirus infection (four primary and three recurrent infections) and in eight patients with asymptomatic human cytomegalovirus recurrent infection. These endomyocardial biopsy specimens showed grade 0 (n = 9), 1A (n = 12), 1B (n = 7), or 2 (n = 2) acute rejection. No myocarditis with human cytomegalovirus-like inclusion bodies was observed by routine histologic evaluation. Human cytomegalovirus DNA or antigens were not shown by in situ hybridization or by immunohistochemical evaluation, respectively. Viral DNA was detected by polymerase chain reaction in two grade 1A endomyocardial biopsy specimens from two patients with systemic human cytomegalovirus primary infection. These two biopsy specimens were shown to be positive by polymerase chain reaction at the time of the acute phase of the infection as shown by laboratory findings. Therefore cytomegalovirus DNA detected by polymerase chain reaction could result from viral carriers, that is, leukocytes of rejection-related infiltrates or within intramyocardial vessels as a result of a more aggressive expression of the systemic infection in seronegative recipients with cytomegalovirus seropositive donors. Polymerase chain reaction is the most sensitive method for viral DNA detection on paraffin embedded biopsy specimens, but a multitechnologic approach, including routine histologic evaluation, is required for a proper diagnosis of human cytomegalovirus myocardial infection. PMID- 7865515 TI - Time course and contact dependence of allogeneic lymphocyte-induced human aortic endothelial cell-derived interleukin-6. AB - Vascular endothelial cells secrete the pluripotent cytokine interleukin-6, and the induction of this secretion can be regulated by a number of other immune related cytokines. To determine whether a cellular alloimmunologic response to vascular endothelial cells alters the expression of interleukin-6 production by endothelial cells, we cocultured peripheral blood lymphocytes with a pool of human aortic endothelial cells. In response to the pool of allogeneic human aortic endothelial cells, lymphocytes from 10 separate donors proliferated to varying degrees after 5 days of coculturing. After 20 hours, human aortic endothelial cell-derived messenger RNA coding for interleukin-6 increased an average of 96% after exposure to allogeneic lymphocytes and the amount of biologically active interleukin-6 released into the media increased 69%. The kinetics of human aortic endothelial cell interleukin-6 messenger RNA expression in response to lymphocytes from an additional three donors was determined over a 48-hour period. Human aortic endothelial cell interleukin-6 messenger RNA increased approximately threefold over control, as early as 2 hours after exposure to allogeneic lymphocytes and returned toward control levels by 48 hours. Activation of six additional isolates of lymphocytes with phorbol myristate acetate before exposure to human aortic endothelial cells resulted in an increase in human aortic endothelial cell-derived interleukin-6 bioactivity regardless of whether the cells were in direct contact with the human aortic endothelial cells, but the interleukin-6 level increase was approximately twofold higher in those cocultures where there was direct contact. These data show that allogeneic lymphocytes have the potential of regulating vascular endothelial cell derived interleukin-6, and direct lymphocyte-endothelial cell contact appears to be required for optimal interleukin-6 induction in this in vitro system. PMID- 7865516 TI - Effect of cryopreservation and HLA-DR matching on the cellular immunogenicity of human cardiac valve allografts. AB - The cellular immunogenicity of fresh and cryopreserved human cardiac valve leaflets was measured in a lymphocyte proliferation assay. One fresh leaflet and a cryopreserved leaflet derived from the same valve were cut into 2 mm diameter pieces and incubated with responder peripheral blood mononuclear cells, matched or mismatched for HLA-DR. The tritiated thymidine incorporation into the lymphocytes measured after 7 days, was expressed as stimulation index. Fresh, HLA mismatched valve pieces induced high stimulation index in all cases (median 9, range 4 to 117). The cryopreservation procedure resulted in a significantly lower stimulation index (p = 0.002, Wilcoxon), with a median stimulation index of 2 (range 0 to 9). In the instances where HLA-DR matched combinations were studied, cryopreservation was also associated with lower stimulation index. HLA matching itself was able to reduce the stimulation index both with cryopreserved and fresh valve pieces as stimulator, resulting in a median stimulation index of 4 (range 2 to 117) for the HLA-DR-mismatched and 1 (range 0 to 5) for the matched lymphocytes (p = 0.006, Wilcoxon). In conclusion, human cardiac valves are able to stimulate immune competent cells in vitro, even after cryopreservation. The cellular allogeneic response in vitro could be an explanation for valve allograft degeneration observed in the clinic. Matching for HLA-DR may reduce these effects. PMID- 7865518 TI - Extended comparison of quality of life between stable heart failure patients and heart transplant recipients. AB - Heart failure has been associated with poor quality of life, which can improve after heart transplantation. Long-term quality-of-life comparisons between patients with heart failure stabilized with medical therapy and heart transplant recipients have not been performed. We assessed quality of life at the time of heart transplantation evaluation and again after 41 months in 12 patients with advanced heart failure stabilized with medical therapy and in 19 patients who had gone on to undergo heart transplantation. Quality of life was measured by three questionnaires. Both groups had similar quality-of-life and clinical features during the transplantation evaluation. Over time, feelings of anxiety and depression, psychologic adaptation, and perceived functional capability improved in the transplant recipients. However, transplant recipients reported more weakness after surgery; this was the major symptom that limited activities. At follow-up 41 months later, we found no significant differences in quality-of-life changes over time between patients stabilized with medical therapy and heart transplant recipients. Overall quality of life for patients who remain stable while receiving medical therapy may not be significantly different from patients who have undergone transplantation. PMID- 7865517 TI - University of Wisconsin solution provides superior myocardial preservation compared with Stanford cardioplegic solution. AB - The efficacy of the University of Wisconsin solution to safely prolong preservation times for kidney, pancreas, and liver transplantation is established, but its efficacy in enhancing myocardial preservation is not yet clear. We studied the effects of Stanford cardioplegic solution and the University of Wisconsin solution both in preserving the myocardium and in protecting it from the effects of reperfusion injury after 6 hours of preservation. In 28 rat hearts we measured changes in high-energy phosphate content (with magnetic resonance spectroscopy) and histologic changes (edema, endothelial changes, myocyte architecture) during preservation and changes in high-energy phosphate content, histologic status, and performance (aortic systolic and diastolic pressure, heart rate, rhythm) in Langendorff and working hearts during reperfusion. No significant differences in the kinetics of high energy phosphate changes were noted between the two cardioplegic solutions during preservation. However, at the end of 6 hours of preservation, hearts in the Stanford cardioplegic solution group were more edematous (p < 0.01) than those in the University of Wisconsin group. During reperfusion, no significant differences in the kinetics of high-energy phosphates were noted between the two cardioplegic solutions. None of the hearts in the University of Wisconsin solution group developed ventricular fibrillation at the start of reperfusion, but all hearts in the Stanford group did so. Once sinus rhythm was established no significant differences in developed pressure or heart rate were found between the two solutions. After 2.5 hours of reperfusion, hearts in the Stanford group were more edematous (p < 0.002) and had a greater disruption of myocyte architecture (p < 0.002) and greater arteriolar endothelial injury (p < 0.004). In conclusion, the University of Wisconsin solution better protects the myocardium in this rat model than does Stanford solution. The mechanism for this beneficial effect of the University of Wisconsin solution appears to be due to its better preservation of the microvasculature rather than differences in preservation of high-energy phosphates. PMID- 7865519 TI - Does rapidity of development of transplant coronary artery disease portend a worse prognosis? AB - We postulated that transplant coronary artery disease with rapid progression to more than 50% stenosis within a 1-year interval may have a different prognosis from transplant coronary artery disease with a more indolent rate of progression. Annual coronary angiograms of 139 consecutive patients who underwent transplantation between January 1968 and February 1990 who survived at least 1 year after transplantation and in whom angiographically apparent transplant coronary artery disease developed were included in the study. Of this group, 45 patients progressed from a normal angiogram to the presence of 50% or greater stenosis in one or more major vessels within 1 year (fulminant group); 94 did not (indolent group). Mean posttransplantation follow-up time was 5.3 +/- 4.1 years for patients with fulminant progression of disease and 6.6 +/- 3.7 years for those with indolent progression. A highly significant difference was found in the time-related incidence of ischemic events (myocardial infarction, congestive heart failure, sudden death, and retransplantation) between the indolent and the fulminant groups after initial detection of transplant coronary artery disease. At 1, 3, and 5 years after initial detection of transplant coronary artery disease, 50%, 33%, and 16% of patients in the fulminant group and 89%, 70%, and 60% of patients in the indolent group were free of ischemic events (p < 0.0001). The fulminant group of patients had a mean of 2.9 +/- 1.5 rejection episodes, and the indolent group a mean of 2.3 +/- 1.4 episodes (p = 0.02) during the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865520 TI - Recovery of major organ function in patients awaiting heart transplantation with Thoratec ventricular assist devices. Thoratec Ventricular Assist Device Principal Investigators. AB - The time course of recovery of hepatic and renal function was determined in 193 patients receiving Thoratec ventricular assist devices while awaiting transplantation at 41 hospitals in eight countries. The duration of circulatory support averaged 26 days (maximum 248 days) and the average ventricular assist device blood flow index was 2.7 +/- 0.5 L/min/m2 compared with a preoperative cardiac index of 1.4 +/- 0.7 L/min/m2. Renal and hepatic function improved in most patients in 1 to 3 weeks of support. When comparing patients with the longest durations on the ventricular assist device (60 to 248 days) to patients with the shortest durations (< 7 days), laboratory values were significantly improved: creatinine (-29%, from 1.7 +/- 1.2 to 1.2 +/- 0.5 mg/dl), blood urea nitrogen (-32%, from 37 +/- 27 to 25 +/- 14 mg/dl), serum glutamic-oxaloacetic transaminase (-81%, from 397 +/- 702 to 76 +/- 45 IU) and total bilirubin (-79%, from 7.0 +/- 8.6 to 1.5 +/- 0.7 mg/dl). However, the posttransplantation survival through hospital discharge was not significantly different: 88% (14 of 16) for patients supported for at least 60 days and 86% (43 of 50) for patients who underwent transplantation after only 1 week of support. Therefore renal and hepatic function improve during ventricular assist device support, but the survival rate after transplantation is not related to duration and is comparable to that of conventional heart transplantation for short or long periods of ventricular assist support. Although it is clearly important not to proceed to transplantation in patients with irreversible organ failure who have ventricular assist devices, these data suggest that as long as the patient is on the path to recovery, the outcome is basically the same as for patients who have full recovery of renal and hepatic function. PMID- 7865521 TI - Hemopump fails as bridge to transplantation in postinfarction ventricular septal defect. AB - From 1990, six patients were bridged to transplantation with a catheter-mounted axial flow pump (Hemopump). Indications were graft failure (two patients), postinfarction ventricular septal defect (two patients), myocarditis (1 patient), and myocardial infarction (1 patient). The 21F cannula, inserted via the groin, was used as a partial assist in four patients, and the 31F cannula, inserted via the ascending aorta, was used to assist the other two patients completely. Hemodynamic recovery was achieved in all patients (mean cardiac index rose from 2.1 L/gm/m2 to 3.85 L/gm/m2 after 1 hour assist). Sudden pump failure occurred in the two patients with postinfarction ventricular septal defect and a piece of necrotic tissue blocking the catheter was found. Both patients died. The other four patients were successfully bridged to transplantation. One of these patients died during his postoperative hospital stay; the three remaining patients were discharged and were well at follow-up (46, 40, and 3 months). The Hemopump device provides sufficient organ perfusion to be used as a bridge to transplantation. No conclusions can be drawn for the long-term use (longest run in this series was 102 hours). Postinfarction ventricular septal defect is a contraindication for the use of the Hemopump device. PMID- 7865522 TI - Donors with a history of cocaine use: effect on survival and rejection frequency after heart transplantation. AB - The frequency of cocaine use among donors is currently unknown. Cocaine has cardiotoxic effects and could affect the outcome of heart transplantation. To examine the frequency of nonintravenous cocaine use in organ donors and the outcome of heart transplantation with such donors, we retrospectively analyzed the clinical, biopsy, and donor information on 112 consecutive patients who underwent transplantation between December 1988 and August 1993. Ten patients were excluded because of incomplete information regarding the donor's cocaine status. Of the remaining 102 patients, 16 (16%) had a positive donor history for nonintravenous cocaine use (cocaine group) and 86 patients (84%) had a negative history (noncocaine group). Survival, frequency of cellular rejection (grade > or = 1B), and humoral rejection were compared between the two groups. Survival rates at 30 days (100% versus 97% +/- 2%) and at 1 year (93 +/- 7% versus 89 +/- 3%) were similar (p = not significant, cocaine versus noncocaine group). Freedom from rejection was similar at 30 days (81% +/- 10% versus 79% +/- 4% cellular rejection-free, 33% +/- 14% versus 60% +/- 6% humoral-free) and 6 months (34% +/- 12% versus 55% +/- 5% cellular-free, 16% +/- 11% versus 36% +/- 6% humoral-free) (p = not significant). No significant difference was found in donor inotropic support before procurement, ischemic time, length of stay in intensive care unit, or total stay in the hospital. In conclusion, a high incidence of nonintravenous cocaine use exists among donors. The outcome of patients who receive transplanted hearts obtained from nonintravenous cocaine users is favorable, suggesting that the use of such hearts is safe. PMID- 7865523 TI - Possible association between the observed cyclosporine-induced upregulation of in vitro immune functions and posttransplantation lymphoproliferative disorders. PMID- 7865524 TI - Value of endomyocardial biopsy in the diagnosis of lymphoproliferative disorder after heart transplantation. PMID- 7865525 TI - Thrombotic complications after heart transplantation. PMID- 7865526 TI - Breath pentane and heart rejection. PMID- 7865527 TI - Long-term results of combined heart-lung transplantation: the Stanford experience. AB - We assessed the long-term results of our experience with 109 patients with end stage cardiopulmonary disease who underwent primary combined heart-lung transplantation at Stanford University Medical Center between March 1981 and January 1994. Average recipient age was 31 +/- 10 years (mean +/- standard deviation) median, 31 years; range, 1 month to 52 years. Recipient diagnoses included primary pulmonary hypertension (31%), Eisenmenger's syndrome (39%), complex congenital heart disease (8%), cystic fibrosis (14%), bronchiectasis (2%), and emphysema (3%). Immunosuppression was with cyclosporine and a tapering regimen of corticosteroids. In 1986 azathioprine was added, and since 1987 induction therapy with OKT3 has been employed. Actuarial survival rates at 1, 5, and 10 years were 68% +/- 4.6%, 43% +/- 5.4%, and 23% +/- 8.1%, respectively (mean +/- 1 standard error of the mean). Fourteen deaths occurred in the hospital for an operative mortality rate of 12.8% +/- 3.3%, and 61 deaths occurred overall. Causes of death included hemorrhage (five patients), infection (21), rejection (one), nonspecific pulmonary failure (four), graft coronary artery disease (six), and obliterative bronchiolitis (eight). Infection, rejection, and obliterative bronchiolitis were the major complications. Only 20% +/- 3.9% of patients were free from any infection 3 months after transplantation. Heart and lung rejection commonly occurred asynchronously; actuarial estimates of freedom from isolated lung rejection at 1 and 5 years were 47% +/- 5.2% and 40% +/- 5.6%, respectively. For simultaneous heart and lung rejection these estimates were 87% +/- 3.5% and 86% +/- 3.8%, and for isolated heart rejection 63% +/- 5.1% and 51% +/- 6.4%, respectively. Although graft coronary artery disease developed less frequently than in patients after isolated heart transplantation (90% +/- 4.6% of patients were free of graft coronary artery disease at 5 years), obliterative bronchiolitis remains a major long-term complication and cause of morbidity and mortality. Actuarial estimates of freedom from obliterative bronchiolitis at 1, 5, and 10 years were 71% +/- 5.1%, 51% +/- 6.1%, and 42% +/- 7.8%, respectively. These results show satisfactory early and medium-term outcome after combined heart-lung transplantation but also underscore that much progress is needed in controlling infection, rejection, and obliterative bronchiolitis, all of which remain as major impediments to long-term survival. PMID- 7865528 TI - Heart transplantation in Spain: the Spanish National Registry of Heart Transplantation (1984-1992). AB - The first heart transplantation in Spain was performed in 1984. Since then, 950 patients had undergone heart transplantation in our country as of December 1992. Data from all these 950 patients have been reported to the Spanish National Registry of Heart Transplantation since its inception in 1989. Follow-up is complete for all patients. Mean age of recipients was 46 +/- 14 years; 86% were male patients. Almost 50% of all heart transplant procedures were performed in 1991 (232 patients, 6 per million persons) and 1992 (254 patients, 6.6 per million). Twelve centers have performed heart transplantations in Spain. Of the 950 procedures, 907 (95%) have been orthotopic, 6 (0.6%) heterotopic, 16 (1.7%) heart-lung transplantations, and 21 (2.7%) retransplantations. Mortality on waiting list was 8% in 1991 and 5.2% in 1992. Idiopathic (47%) and ischemic (37%) cardiomyopathy were the two main causes leading to transplantation. Mean recipient age has increased from 38 years in 1985 to 50 in 1992; 50% of all patients who underwent transplantation in 1992 were older than 50 years of age, with 11% older than 60 years of age. Actuarial survival was 74% at 1 year and 63% at 6 years, which is similar to that of the International Society for Heart and Lung Transplantation Registry. One-year survival increased from 61% for patients receiving transplants in 1985 to 77% for those who received transplants in 1992. One-month mortality decreased from 23% in 1985 to 12% in 1992.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865529 TI - Monitoring of acute lung rejection and infection by bronchoalveolar lavage and plasma levels of hyaluronic acid in clinical lung transplantation. AB - Local immunological injury caused by acute lung rejection leads to fibroblast proliferation. Hyaluronate is a product of activated fibroblasts and possibly an indicator of fibroblast proliferation. One hundred thirty-six bronchoalveolar lavage and plasma hyaluronate assays were performed in 57 lung transplant recipients. Pulmonary endothelial cell function was assessed by measuring bronchoalveolar lavage levels of purine nucleoside phosphorylase. Presence of acute cellular rejection was monitored by transbronchial biopsy histologic evaluation and was classified as minimal to mild (acute rejection I, II) and moderate to severe (acute rejection III, IV). Infection was confirmed by bronchoalveolar lavage culture and antibiotic sensitivity. Bronchoalveolar lavage hyaluronate levels in clinically stable recipients were 33.5 +/- 4.69 micrograms/L and were significantly higher than with clinically stable recipients (p = 0.0001), infection (p = 0.008), or mild rejection (p = 0.001). Levels were highest in recipients with diffuse alveolar damage (392.4 +/- 60.6 micrograms/L). Diffuse alveolar damage also resulted in significant elevations of plasma HA as compared with stable recipients (p = 0.001) and mild rejection. We conclude that clinically significant injury to the allograft from rejection or diffuse alveolar damage can be assessed by bronchoalveolar lavage hyaluronate assays and suggest that the source of hyaluronate in these instances are activated fibroblasts. PMID- 7865530 TI - Evaluation of transbronchial lung biopsy specimens in the diagnosis of bronchiolitis obliterans after lung transplantation. AB - We investigated the utility of transbronchial lung biopsy in allograft evaluation, particularly with reference to rejection-mediated bronchiolitis obliterans in 105 transplant recipients surviving 3 months or more (29 single lung, 76 double lung). A sensitivity and specificity of one transbronchial biopsy procedure with an average procurement of 7.6 tissue fragments was 17.1% and 94.5%, respectively, according to results obtained from biopsies carried out after 2 months transplantation in 29 patients with confirmed rejection-mediated bronchiolitis obliterans and 61 patients known not to have the disease. The predictive value of a positive procedure for the presence of disease was 65.5% and that of a negative procedure for the absence of disease was 65.2%. Similarly, the sensitivity and specificity for the finding of bronchiolar mural fibrosis were 18.5% and 85.3%, respectively; and, for lymphocytic bronchiolitis, the values were 1.9% and 100%, respectively. We conclude that, although the sensitivity of transbronchial biopsy and the predictive value of a procedure which shows microscopic bronchiolitis obliterans are low, attempts should be made to support a clinical diagnosis of bronchiolitis obliterans through biopsy, given the problems inherent in achieving an early and certain diagnosis according to clinical criteria alone. PMID- 7865531 TI - Differential soluble interleukin-2R levels in bilateral bronchoalveolar lavage after single lung transplantation. AB - Preliminary reports suggest that measurement of the soluble 55 kd subunit of the interleukin-2 receptor may facilitate the diagnosis of allograft rejection in solid organ transplants. Levels of soluble interleukin-2 receptor in serum or plasma have previously lacked sufficient sensitivity and specificity for the diagnosis of acute allograft rejection. Because single lung transplantation is preferentially performed for nonseptic end-stage pulmonary and cardiopulmonary maladies, we questioned whether the pattern of soluble interleukin-2 receptor recovery in bronchoalveolar lavage fluid obtained from both the native and transplanted lungs may enhance correct diagnosis. Fifty-three consecutive fiberoptic bronchoscopic procedures were performed with bilateral bronchoalveolar lavage fluid. Transbronchoscopic biopsies were histologically classified by the International Society for Heart Transplantation Working Formulation for Standardized Nomenclature. "Soluble interleukin-2 receptor index" was calculated as the quotient of soluble interleukin-2 receptor (in units per milliliter) by enzyme-linked immunosorbent assay, divided by protein (in milligrams per milliliter) to correct for differences in bronchoalveolar lavage fluid techniques and cellularity. Soluble interleukin-2 receptor indexes were significantly increased in the allograft bronchoalveolar lavage fluid during histologic grade A (acute rejection) versus normal transbronchoscopic biopsy specimens (3395 +/- 1298 U/mg versus 76 +/- 21 U/mg) associated with an increased transplanted/native lung ratio (69.9 +/- 46 versus 2 +/- 1 [mean +/- standard error of the mean]) (one-way analysis of variance, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865532 TI - Early biochemical indicators of the obliterative bronchiolitis syndrome in lung transplantation. AB - The diagnosis of the obliterative bronchiolitis syndrome in lung transplantation is presently best established by evaluation of postoperative lung function tests. Unfortunately the decline in lung function occurs only when obliteration has progressed significantly and is therefore not an early predictive indicator. To distinguish patients at increased risk for the development of obliterative bronchiolitis, we regularly assessed the chemiluminescence response of polymorphonuclear leukocytes, opsonic capacity, and plasma elastase/beta-N acetylglucosaminidase in 52 outpatients (25 women and 27 men; mean age 45 +/- 12 years) who underwent transplantation between January 1991 and January 1992. Recent onset bronchiolitis within the described observation period occurred in 16 patients (group obliterative bronchiolitis). A matched cohort of 16 patients was formed according to type of procedure, age and follow-up (control) from the remaining 36 patients. Data obtained from a period 6 months before clinical onset of the syndrome showed a significant drop of the opsonic capacity (group obliterative bronchiolitis = 87% +/- 7%; control = 100% +/- 9%; p < 0.023) and rise of the N-acetyl-D-glucosaminidase (group obliterative bronchiolitis = 7.5 +/ 2 U/L; control = 5.8 +/- 1.8 U/L; p < 0.04). No correlation was found between the number of infectious events or rejection episodes and the incidence of obliterative bronchiolitis. According to these results, it can be concluded that a decrease in the plasma opsonic capacity and a rise in beta-N acetylglucosaminidase may be early markers before clinical onset of obliterative bronchiolitis. The nonspecific immune system may therefore play an important role in the development of obliterative bronchiolitis. PMID- 7865533 TI - University of Wisconsin solution for lung graft preservation: which components are important? AB - Rat lung grafts were perfused with either Euro-Collins solution, University of Wisconsin solution, or one of six modified University of Wisconsin solutions that had been sequentially depleted of specific components (n = 5 each group). After storage at 4 degrees C for 6 hours, the isolated, ventilated pulmonary graft was reperfused for 1 hour with recirculating venous blood from a support animal. In a further group, lungs were reperfused immediately after explanation to provide control values. Grafts flushed with University of Wisconsin solution functioned at control levels with regard to oxygen tension: University of Wisconsin solution 128 +/- 2.7 mm Hg, control 126 +/- 5 mm Hg; graft blood flow: University of Wisconsin solution 9.9 +/- 0.4 ml/min, control 10.2 +/- 0.8 ml/min; peak airway pressure: University of Wisconsin solution 17 +/- 0.5 mm Hg, control 16.5 +/- 0.6 mm Hg; and weight gain: University of Wisconsin solution 0.12 +2- 0.1 gm, control 0.19 +/- 0.13 gm. In contrast, lungs treated with Euro-Collins solution functioned less well: oxygen tension 54 +/- 6 mm Hg, graft blood flow 3.5 +/- 0.42 ml/min, peak airway pressure 35 +/- 4 mm Hg, and weight gain 4.15 +/- 0.5 gm (p < 0.0001 all parameters). Sequential removal of hydroxyethyl starch, magnesium, allopurinol, adenosine, glutathione, and lactobionate from University of Wisconsin solution did not impair the efficacy of the solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865534 TI - Protection against lipid peroxidation induced during preservation of lungs for transplantation. AB - The questions of whether oxygen-derived free radicals are induced during preservation of lungs and, if so, how such radicals might relate to reperfusion injury were investigated by means of an isolated canine lung model. Lungs were obtained from 16 mongrel dogs and divided into groups 1 (n = 6), 2 (n = 5), and 3 (n = 5). The lungs of groups 1, 2, and 3 were flushed through the pulmonary artery with Euro-Collins solution alone, the solution with superoxide dismutase (120,000 U/L), and the solution with allopurinol (1 mmol/L), respectively, at 4 degrees C and then stored for 4 hours in the respective solutions at 4 degrees C with clamped bronchi. They were then reperfused for 2 hours by means of an isolated lung model. Lung lipid peroxidation was sequentially determined. The lung functional status was assessed by systolic pulmonary arterial pressure and end-inspiratory airway pressure. The lung edema was assessed by lung wet/dry weight ratio. Lipid peroxidation was induced after 1 hour of preservation and the first 30 minutes of the reperfusion in group 1 and only 2 hours of the reperfusion in group 2, whereas no induction was observed in group 3. Values for systolic pulmonary arterial pressure and end-inspiratory pressure in group 1 were significantly higher than those in group 3 (p < 0.05). The lung wet/dry weight ratio in group 1 was significantly higher than that in groups 2 and 3 (p < 0.05). The present results indicate that the administration of free radical scavengers in the preservation may effectively improve conditions for lung transplantation. PMID- 7865535 TI - Atomic force microscope images of lipid layers spread from vesicle suspensions. AB - The layer formation of unilamellar vesicles of L-alpha-dimyristoyl phosphatidylcholine (DMPC) spread onto the air/liquid interface has been investigated. The layers were transferred to clean glass slides and onto slides made hydrophobic with multilayers of Cd arachidate. Aged vesicle suspensions aggregate during storage and are transferred as large domains as imaged with atomic force microscopy (AFM). Freshly prepared vesicles fuse and can be transferred as monolayers to hydrophobic supports. Furthermore, AFM images reveal the importance of positioning the solid support parallel to the moving barrier in order to obtain more uniform deposition of Cd arachidate. PMID- 7865536 TI - Phospholipase activities associated with the tonoplast from Acer pseudoplatanus cells: identification of a phospholipase A1 activity. AB - The study of phospholipase activities associated with the tonoplast of Acer pseudoplatanus was performed in vitro with sn-2-[14C]acylphosphatidylcholine (PC) as a substrate. The hydrolysis of radiolabelled PC into [14C]phosphatidic acid and [14C]lyso-PC demonstrated the presence of phospholipase D and A1 activities, respectively, associated with the tonoplast of Acer pseudoplatanus. The vacuolar sap did not show any significant phospholipase activity. In a second step, the properties of the phospholipase A1 activity was studied using tonoplast endogenous PC labelled in vivo with [14C]choline as a substrate. The phospholipase A1 showed an optimal activity at pH about 6-6.5, did not necessarily require divalent cations, but was stimulated by Mg2+ and particularly by Ca2+. This work presents the first evidence for the presence of phospholipases A1 in plant cells. PMID- 7865537 TI - (Galacto) lipid export from envelope to thylakoid membranes in intact chloroplasts. II. A general process with a key role for the envelope in the establishment of lipid asymmetry in thylakoid membranes. AB - The transfer of organelle of newly synthesized lipid molecules from inner envelope to thylakoid membranes, as well as their subsequent transbilayer distribution in these membranes, have been studied in intact chloroplasts isolated from young and mature spinach, young pea and mature lettuce leaves, using a recently developed methodology (Rawyler, A., Meylan, M. and Siegenthaler, P.A. (1992) Biochim. Biophys. Acta 1104, 331-341). Three radiolabelled precursors were used. UDP-[14C]galactose allowed to follow the fate of mono- and digalactosyldiacylglycerol (MGDG and DGDG) made from polyunsaturated, preexisting diacylglycerol (DAG), whereas [14C]acetate and [14C]glycerol 3-phosphate were used to follow the fate of MGDG and phosphatidylglycerol (PG), respectively, after de novo synthesis. MGDG, DGDG and PG molecules assembled at the envelope level were found to be exportable to thylakoids in amounts strictly proportional to the amounts synthesized, provided that the necessary substrates were not limiting. Lipid export was class-selective; under our conditions, as much as 50 80% of the MGDG, 87% of the PG and 20-30% of the DGDG synthesized were exported to thylakoids. However, within the MGDG class labelled from [14C]acetate, there was hardly any selectivity in the export of its various molecular species. For MGDG, the proportionality coefficient, which reflects the efficiency of the export process, was higher in chloroplasts from young than from mature leaves, and higher in spinach than in pea and lettuce. Temperature affected the efficiency of galactolipid export in a class-dependent way. MGDG synthesis and export had similar Q10 values of about 4 in young and 3 in mature spinach leaves, while the Q10 of DGDG export was higher than that of its synthesis. In most cases, the transmembrane distribution of labelled lipids in thylakoids was found to match closely the corresponding distribution of mass, regardless of plant age and species and of incubation time and temperature. In some cases however, small but significant differences occurred between the label and the mass transbilayer distributions of MGDG (labelled molecules more inwardly oriented), DGDG and PG (more outwardly oriented). We propose a general model in which the thylakoid lipid asymmetry is primarily preestablished in the chloroplast envelope by the topography of its lipid-synthesizing enzymes, together with the occurrence of relatively fast lateral diffusion and translocation rates of the newly synthesized lipids. Transient fusions between inner envelope and thylakoid membranes would allow lipid export by lateral diffusion and build the observed lipid asymmetry in the latter. PMID- 7865538 TI - Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro. AB - Receptors for the vitamin folic acid are frequently overexpressed on epithelial cancer cells. To examine whether this overexpression might be exploited to specifically deliver liposome-encapsulated drug molecules in vitro, folate targeted liposomes were prepared by incorporating 0.1 mol% of a folate polyethyleneglycol-distearoylphatidylethanolamine (folate-PEG-DSPE) construct into the lipid bilayer, and were loaded with doxorubicin (DOX), an anti-cancer drug. Uptake of folate-PEG-liposomal DOX by KB cells was 45-fold higher than that of non-targeted liposomal DOX, and 1.6-times higher than that of free DOX, while the cytotoxicity was 86 and 2.7-times higher, respectively. Folate-targeting is fully compatible with PEG-coating of the liposomes, since incorporation of 4 mol% PEG2000-DSPE does not reduce the uptake or cytotoxicity of folate-PEG-liposomal DOX. Uptake of folate-PEG-liposomes was inhibited by 1 mM free folic acid but was unaffected by physiological concentrations of folate. In HeLa/WI38 co-cultures, folate-PEG-liposomes encapsulating calcein, a fluorescent dye, were found to be almost exclusively internalized by the HeLa cells which overexpress the folate receptors. We suggest that folate targeting constitutes a possible mechanism for improving the specificity of PEG-coated liposomes for cancer cells. PMID- 7865539 TI - Target size analysis of the peptide/H(+)-symporter in kidney brush-border membranes. AB - The apparent functional molecular mass of the kidney peptide/H(+)-symporter was determined by radiation inactivation in brush-border membrane vesicles (BBMV) of rat kidney cortex. Purified BBMV were irradiated at low temperatures with high energy electrons generated by a 10-MeV linear accelerator at doses from 0 to 30 megarads. Uptake studies were performed with [3H]cefadroxil, a beta-lactam antibiotic which serves as a substrate for the kidney peptide/H(+)-symporter. Inhibition of influx of [3H]cefadroxil into BBMV was used to determine the functional molecular mass of the transporter. Additionally, direct photoaffinity labeling of the transport- and/or binding proteins for [3H]cefadroxil in control and irradiated BBMV was performed to determine the molecular mass of the putative transporter by SDS-polyacrylamide gel electrophoresis. Initial rates of pH gradient dependent uptake of [3H]cefadroxil decreased progressively as a function of radiation dose. The apparent radiation inactivation size (RIS) of the transport function was found to be 414 +/- 16 kDa. Direct photoaffinity labeling yielded labeled membrane proteins with apparent molecular masses of 130 kDa and 105 kDa, respectively. The proteins displayed different labeling characteristics with respect to incubation time, specificity and the response to irradiation. It appears that only a 105 kDa protein is directly involved in transport function since (a) only it showed a specific pH gradient dependent labeling pattern and (b) the covalent incorporation of [3H]cefadroxil into this protein decreased parallel to the loss of transport function in irradiated BBMV. The peptide/H(+) symporter in kidney brush-border membranes therefore appears to have a monomer mass of 105 kDa and may function in an oligomeric arrangement. PMID- 7865540 TI - Novel regulations of glutamate and aspartate uptake by HeLa cells. AB - Pathways of L-glutamate and L-aspartate import by HeLa S3 cells were investigated before and after the cells were depleted of internal amino acids by starvation. Two new regulations of transport were observed in starved cells. Aspartate entered nonstarved cells by two routes, one non-saturable and one, an apparent analog of saturable system X-AG, that was sodium-dependent and competitively inhibited by glutamate. Starvation for one hour in saline increased the efficiency of saturable aspartate import, increasing Vmax and decreasing Km, an effect not previously reported for system X-AG. Glutamate uptake by nonstarved cells appeared to occur through system X-AG; through an analog of system X-C, which was sodium-independent, cystine- and quisqualate-inhibitable; as well as through one or more nonsaturable pathways. Starvation in saline for one hour resulted in the appearance of a new low-affinity saturable glutamate uptake system. This new system was sodium-dependent but not inhibited by aspartate. PMID- 7865541 TI - Determination of the sidedness of the carboxy-terminus of the Na+/K(+)ATPase alpha-subunit using lactoperoxidase iodination. AB - The orientation of the carboxy-terminal pair of tyrosines of the Na+/K(+)-ATPase alpha-subunit with respect to the plane of the plasma membrane was determined. The approach was based on lactoperoxidase-catalysed radioiodination of the tyrosine residues accessible on the surface of the enzyme molecule in intact cells of a pig kidney embryonic cell line and those accessible in a broken plasma membrane fraction and in isolated membrane-bound Na+/K(+)-ATPase. The labeled alpha-subunit was isolated by SDS gel electrophoresis followed by electroblotting. Then the COOH-terminal amino acids were hydrolyzed by carboxypeptidases B and Y. Radioactivity and quantitative analysis of the protein and released amino acids showed that the COOH-terminal tyrosine residues of the alpha-subunit were only accessible to modification only when lactoperoxidase had access to the inner side of the plasma membrane. Therefore, the COOH-terminus of the Na+/K(+)-ATPase alpha-subunit is located on the cytoplasmic surface of the pump molecule and its polypeptide chain must have an even number of transmembrane segments. PMID- 7865542 TI - Effects of light and inhibitors of ATP-synthesis on the chloride carrier of the alga Valonia utricularis: is the carrier a chloride pump? AB - The effect of metabolic inhibitors, such as cyanide, antimycin A and azide was studied on the chloride transport system of the giant marine alga Valonia utricularis by using the charge pulse relaxation method. Two clearly defined voltage relaxations were resolved. The addition of 10-30 microM cyanide to the artificial sea water (ASW) bathing the algal cells increased the time constants of the slow voltage relaxation, tau 2, significantly when the algal cells were kept in the dark. The cyanide-effect reached a plateau value at 100-300 microM and was fully reversible when cyanide was removed from the ASW. Analysis of the charge pulse data in terms of the Lauger-model demonstrated that the translocation rates of the free, kS, and the charged carrier, kAS, decreased. The decrease of kS was more pronounced than that of kAS. 10 microM antimycin A and 3 mM azide had similar effects on the rate constants when the light was switched off. Upon illumination the cyanide- and antimycin A-, but not the azide-mediated effects disappeared. At concentrations higher than 1 mM cyanide caused a further, dramatic decrease of kS and kAS, while the surface concentration of the carrier molecules, N0, was not affected. This cyanide-effect was also reversible, but not light-dependent. Measurements of the ATP level showed that 3 mM cyanide reduced the ATP level by about 70% both under light and dark conditions. In the presence of 30 microM cyanide (or 10 microM antimycin A) the ATP level decreased by about 50%, but only in the dark. These results suggest two different effects of cyanide on the Cl(-)-carrier system: in the micromolar concentration range cyanide (and antimycin A) reduced predominantly the translocation of the free carrier by inhibition of ATP synthesis by oxidative phosphorylation, whereas in the millimolar concentration range cyanide apparently inhibits the translocation rates of both the free and charged carriers by its binding to the carrier. The results provide some evidence that the chloride transport of V. utricularis could be coupled to metabolic energy but it is an open question whether it is a pump or not. PMID- 7865543 TI - A quantitative electrophoretic migration shift assay for analyzing the specific binding of proteins to lipid ligands in vesicles or micelles. AB - We present a new assay for analyzing the specific binding of proteins to lipid ligands contained within vesicles or micelles. This assay, referred to as the electrophoretic migration shift assay, was developed using a model system composed of cholera toxin and of its physiological receptor, monosialoganglioside GM1. Using polyacrylamide gel electrophoresis in non-denaturing conditions, the migration of toxin components known to interact with GM1 was retarded when GM1 was present in either lipid vesicles or micelles. This effect was specific, as the migration of proteins not interacting with GM1 was not modified. The localization of retarded proteins and of lipids on gels was further determined by autoradiography. The stoichiometry of binding between cholera toxin and GM1 was determined, giving a value of five GM1 per one pentameric assembly of cholera toxin B-subunits, in agreement with previous studies. The general applicability of this assay was further established using both streptavidin and annexin V together with specific lipid ligands. This assay is fast, simple, quantitative, and requires only microgram quantities of protein. PMID- 7865544 TI - Multiple components of transport are associated with murine cationic amino acid transporter (mCAT) expression in Xenopus oocytes. AB - Expression of putative amino acid transport proteins is usually assumed to be associated with expression of a single component of transport. It is shown in this report, however, that murine cationic amino acid transporter (mCAT) expression in Xenopus oocytes is associated in important instances with expression of more than one kinetically distinguishable transport process. Accurate knowledge of the kinetics of transport continues, therefore, to be needed to understand how transport proteins function. PMID- 7865545 TI - Renal osteodystrophy with hyperparathyroidism: the diagnostic value of intact parathormone, alkaline phosphatase, osteocalcin and procollagen. AB - In 27 patients on periodic haemodialysis, serum levels of alkaline phosphatase (ALP), osteocalcin (BGP), intact parathyroid hormone (PTHi) and its two fragments, terminal COOH (PTH-Cter) and middle molecule (PTH-MM), and procollagen type 1 carboxy-terminal extension peptide (P1CP) were measured. The same patients underwent radiography of the skull and of the hands, ultrasonography of the parathyroids and scintigraphy of the skeleton with 99mTc-MDP. The study was completed by the measurement of aluminium (Al) in the blood and the deferoxamine test (DFO). Two groups of patients emerged, one (group A, n = 14) with PTHi greatly increased (201.07 +/- 109.72 pg/mL) and the other (group B, n = 13) with values within the normal range (32.69 +/- 17.06 pg/mL) (p < 0.001). In group A, ALP, BGP and particularly P1CP were increased with a statistically significant difference compared to group B. Specific radiographic alterations were found in 12 patients of group A; 7 patients also had hypertrophy of the parathyroids. There was no difference in the scintigraphic alterations of the skeleton between the two groups. The authors conclude that it is the association of the high values of PTHi with those of the markers of bone metabolism, the normal level of Al, the negativity of the DFO test and the radiological alterations which together allow the diagnosis of renal osteodystrophy with hyperparathyroidism. PMID- 7865546 TI - Maldistribution of regional myocardial perfusion at rest in patients with coronary artery disease and no previous myocardial infarction, evidenced by 99mTc Sestamibi scintigraphy. AB - Since myocardial 99mTc-Sestamibi uptake is closely related to coronary blood flow and the tracer does not redistribute, resting perfusion defects may be observed even in viable regions supplied by vessels with severe stenosis. The incidence and the clinical significance of 99mTc-Sestamibi uptake defects at rest were investigated in 60 men with suspected coronary artery disease and no previous myocardial infarction, in a multicenter study. Of 60 patients, 12 showed normal coronary arteries and 48 significant coronary artery disease (> 50% luminal narrowing). Based on the presence or absence of tracer uptake defects at resting planar scans, the patients were divided into Group 1 (27 patients) and Group 2 (33 patients), respectively. A greater incidence of coronary artery disease (100% versus 64%, p < 0.01) and of multivessel disease (70% versus 36%, p < 0.05) was observed in patients of Group 1. All patients underwent dipyridamole (up to 0.84 mg/kg in 10 min) 99mTc-Sestamibi scintigraphy, which more frequently induced transient 99mTc-Sestamibi uptake defects in Group 1 than in Group 2 (85% versus 42%, p < 0.001). A high incidence of resting 99mTc-Sestamibi uptake defects was observed in patients without previous myocardial infarction; this identified a subset of patients with a higher prevalence of coronary artery disease and multivessel involvement and with a greater impairment of the coronary reserve, as evidenced by a dipyridamole test. PMID- 7865547 TI - Estimate of relative function and transit time in renographic studies. AB - Renal transit time and relative renal function are the most commonly used parameters in the study of renal function. In clinical practice the determination of these two parameters is carried out either using the renal retention function or directly from the renogram. This study seeks to compare the values for the transit time and the relative function, as calculated from the renogram and from the renal retention function, in renographic studies using 131I-OIH and 99mTc MAG3. For both tracers it was found that the estimated renal transit time from the renogram (OIH: 289 +/- 118 s, MAG3: 297 +/- 110 s) generated values that were higher than those obtained from the renal retention function (OIH: 245 +/- 85 s, MAG3: 274 +/- 97 s), with significant differences between the two estimates (p < 0.001). As regards the relative function, there were no significant differences between the estimates obtained from the renogram (58.5 +/- 8.3%) and the renal retention function (59.5 +/- 9.3%) in the case of OIH. For MAG3 the estimate obtained from the renogram (58.3 +/- 6.3%) and from the renal retention function (59.9 +/- 7.1%) were significantly different (p < 0.025). PMID- 7865548 TI - Effects of exercise-induced alterations of cardiac physiology on nuclear perfusion imaging. AB - The effects produced on nuclear perfusion images by exercise-induced changes in the heart and respiration rate and possible transient myocardial stunning are not well understood. In this study we attempted to indirectly evaluate the potential artifacts created by exercise-induced changes in cardiac physiology. Twenty patients with prior myocardial infarction and suspected peri-infarct ischemia were studied by 99mTc-MIBI imaging. Two SPECT perfusion studies were performed after 99mTc-MIBI administration at rest. The first acquisition was carried out 90 minutes after injection of the tracer. Immediately afterwards, the patients underwent a stress test followed by a second acquisition (exercise stress superimposed on rest tracer distribution). A standard stress perfusion scan was also performed 48 hours later. Superimposed exercise stress produced artifactual defects in the resting distribution of the tracer in 15 out of 20 patients (68 of 360 segments). Standard stress images demonstrated concordant defects in 48 of these segments, indicating the concomitant presence of ischemia and stunning. This study indicates that exercise-induced changes in cardiac physiology may result in artifactual perfusion defects in scintigraphic images acquired shortly after the stress. PMID- 7865549 TI - Reverse redistribution of thallium-201 heralding the development of myocardial infarction: description of two cases. AB - Development of a perfusion defect on the 201Tl image from exercise to redistribution is referred to as reverse redistribution, a finding which has been previously associated with several conditions. We describe here two cases in which the reverse-redistribution phenomenon, observed in a routine stress redistribution thallium-201 scan performed because of chest pain, was considered to be artifactual. Both patients subsequently developed a myocardial infarction in the areas showing the delayed perfusion defect. The potential clinical significance of the reverse-redistribution phenomenon in these two cases is discussed. When observed in patients with typical anginal pain, the reverse redistribution pattern should be considered a potential marker of tissue at risk in a region with previous, otherwise undetected, subendocardial infarction. In such patients the need for coronary angiography should be carefully considered. PMID- 7865550 TI - European Community legislation affecting radiopharmaceuticals: cold fusion or illusion? PMID- 7865551 TI - Myocardial perfusion with [11C]methyl triphenyl phosphonium: measurements of the extraction fraction and myocardial uptake. AB - The present study describes extraction fraction and uptake measurements of the [11C]methyl triphenyl phosphonium (11C-MTP), a promising positron emission tomography (PET) agent for cardiac imaging. PET imaging was performed in mongrel dogs. Under physiological flow conditions 11C-MTP uptake reached a maximum within the first 10 minutes after injection and remained constant during the entire observation period of 80 minutes. Over the same time period, the heart/blood ratio was 46-106:1, and the heart/lung ratio 14:1. Following permanent occlusion of the left anterior descending coronary artery, 11C-MTP uptake in the normally perfused myocardium also reached a maximum at 10 minutes after injection, whereas in the infarcted area there was no significant accumulation of 11C-MTP. For a time period of 80 minutes the noninfarcted/infarcted myocardium ratio was 12:1. Extraction was measured in anesthetized dogs with a double isotope method using 99mTc-HSA as the reference tracer. The extraction fraction was 91% at a flow of 69 mL/min/100g. As flow increased to five-fold (342 mL/min/100g) following administration of adenosine, extraction fell to 61%. Following coronary artery occlusion, the 11C-MTP content in the myocardium was highly correlated (r = 0.93, p < 0.01; y = 10.46 + 0.92x) with the microsphere determined regional myocardial blood flow. PMID- 7865553 TI - [Hantavirus disease: an emerging infection]. PMID- 7865552 TI - 99mTc-complexes of a pentadentate amine-oxime ligand. AB - Synthesis and characterization of a new pentadentate amine-oxime ligand, 3,3,11,11-tetramethyl-7-benzyl-4,7,10-triazatridecane-2,12- dionedioxime is reported. The technetium complexes of this ligand was formed by direct reduction of TcO4- in the presence of the ligand at pH 9. The radiochemical yield of the complex is greater than 95% with 10(-7) M 99TcO4-. The technetium complex formed is a positively charged chelate that elutes as a single peak on a reverse phase HPLC. Biodistribution studies in rats showed an uptake of 1.4% of the injected activity at 15 sec p.i. in heart, but the wash-out was fast. The high radiochemical purity and stability of this 99mTc-chelate indicate that these types of chelates hold potential for development of bifunctional chelating agents (BFCAs). PMID- 7865554 TI - [Evaluation of the speed of 3 hemoculture systems to detect bacteria in the blood]. AB - BACKGROUND: The speed of three culture blood systems to detect microbial growth was evaluated with 138 strains isolated from blood which belonged to nine species (N. meningitidis, S. aureus, S. pneumoniae, E. coli, E. faecalis, P. aeruginosa, H. influenzae, A. anitratus and Candida spp.). METHODS: An inoculum of 5-50 UFC were added to each bottle: vials 26 plus with Bactec NR-860 (Becton-Dickinson), aerobial vials with Bact/Alert (Organon) and Hemoline biphasic (bioMerieux). Besides, 10 ml of whole human blood from storage were added to each bottle, too. RESULTS: Bact/Alert was faster in detecting bacterial growth than Bactec with differences statistically significants for all of them, except for H. influenzae. On the other hand, Bactec was faster than Hemoline with differences statistically significant for all bacterial species except S. pneumoniae, which was first detected with manual biphasic method. The median time for detecting growth ranged between 10 h for E. faecalis and A. anitratus in Bact/Alert and 36 h for S. pneumoniae with Bactec. CONCLUSIONS: Bact/Alert detected growth earlier than Bactec, and was quicker than Hemoline. However, other factors have to be in account to choose a method. For instance, biphasic method has the advantage of showing growth in solid medium, whereas automatic systems, at the moment, only use liquid media. PMID- 7865555 TI - [Evaluation of three new culture media: brilliant-glycerol-lactose novobiocin green agar, modified iron lysin agar and Rambach agar for the isolation of enteropathogenic E. coli, Salmonella sp. in acute gastroenteritis]. AB - BACKGROUND: Acute gastroenteritis (AGE) is one of the most common diseases in children, particularly in those under the age of 5 years in whom a severe picture of hydroelectrolyte imbalance may be triggered accompanied, in most cases, by leukocyte response. The aim of this study was to evaluate three new culture media for the isolation of enteropathogens in infantile diarrhea. MATERIAL AND METHODS: From April to September, 1993, 170 samples of diarrhea stools from children up to 7 years of age attending pediatric hospitals in Bogota were studied. Three new culture media were used in the isolation of the enteropathogenic bacteria: BGLN, MILA agar, Rambach agar and a conventional agar medium S.S. Biochemical tests were performed to identify the isolated bacteria. RESULTS: A total of 98.5% of enteropathogenic E. coli was isolated in Rambach agar, which also presented excellent recovery rates of Salmonella sp. (100%) versus S.S> (64.3%) and BGLN (77.2%), respectively. The best selectivity for Shigella sp. was observed with BGLN with a 100% recovery rate. Out of the 170 samples 105 showed a leukocyte count of 70-75% and positive isolation for enteropathogenic bacteria. Six samples with the same leukocyte count did not present enteropathogenic bacteria, with the 59 remaining samples with a 20-25% PMN count being negative for enteropathogenic bacteria. CONCLUSIONS: The results suggest that the new culture media used in this study may have better recovery rates for enteropathogenic bacteria in acute gastroenteritis. Likewise, a correlation was observed between leukocyte count and isolation enteropathogenic bacteria. PMID- 7865556 TI - [Hip prosthesis infection: diagnostic approach and treatment of 27 cases]. AB - BACKGROUND: Preoperative diagnosis of hip prosthesis infection (HPI) is difficult. There is no therapeutic option which is completely effective and without risk. The aim of this study was to evaluate a diagnostic approach and therapeutic strategy in a group of patients with HPI. PATIENTS AND METHODS: A retrospective study of 27 episodes of HPI diagnosed by anatomopathologic and/or microbiologic examination of surgical samples was performed. RESULTS: Twenty three patients with 27 episodes of HPI out of a total of 24 hip prosthesis (HP) were treated. The infection was early in 15 episodes. The etiologic agents were plasmocoagulase negative staphylococcus (NSP) in 11 cases, P. aeruginosa in 8, S. aureus in 5, Enterococcus sp. in 2 and miscellaneous in the remaining cases. In 2 cases the infection was polymycrobial. Following a mean follow period of 22.6 +/- 15.2 months, 13 out of the 14 patients in whom the prosthesis was withdrawn were cured (in 4 a second prosthesis was implanted), one out of 6 in those in whom the prosthesis remained in situ following debridement, and 2 out of 3 episodes in whom reimplantation was performed over time. The withdrawal of the prosthesis was significantly greater than debridement in the treatment of early infection (p < 0.001). The total mean length of postoperative antibiotherapy was 48.2 +/- 17 days. No differences were observed in the oral versus parenteral treatment (p = 0.22), and nor was prognosis worse in those treated for less than 42 days. CONCLUSIONS: The authors' experience suggests that attempts to save a hip prosthesis in early infection usually fail. In addition to prosthesis withdrawal or implantation of another prosthesis, six weeks of postoperative antibiotic therapy, which may be oral route, appear to be sufficient. PMID- 7865557 TI - [Detection of Brucella with an automatic hemoculture system: Bact/Alert]. AB - BACKGROUND: The ability of in vitro and in vivo detection of Brucella spp. with the Bact/Alert system was studied. METHODS: Three strains of Brucella melitensis and two of Brucella abortus were used. Different dilutions of the five strains were performed in trypticase soy broth (TSB), achieving concentrations of 1 cfu/ml, 5 cfu/ml, 10 cfu/ml and 100 cfu/ml. Ten ml of each dilution and strain were inoculated into 5 aerobic bottles Bact/Alert and 5 biphasic Hemoline bottles. Furthermore, over a 9 month period, 8,216 bottles of Bact/Alert bottles from hospitalized patients and from the emergency department were processed in the authors' laboratory. RESULTS: The mean detection time for Brucella growth was from 2 to 3 days with the Bact/Alert system, and 14 days in the biphasic bottles. Former bottles processed in the authors' laboratory, 11 aerobic bottles belonged to 5 patients in whom brucelosis was confirmed by bloodculture. The Bact/Alert system detected Brucella melitensis in only on bottle at 2.9 days of incubation. In 7 bottles Bact/Alert detected B. melitensis by a blind pass of these bottles at 10 to 20 days of incubation. CONCLUSIONS: These results suggest that the Bact/Alert system does not totally solve the diagnosis of brucellosis. Blind passes of the bloodcultures are required. PMID- 7865558 TI - [Comparative study of the serologic response of IgA and IgM type in the diagnosis of acute toxoplasmosis]. AB - BACKGROUND: IgM serologic response in the diagnosis of acute toxoplasmosis presents interpretation problems. A comparative study with IgA detection of antibodies was performed. METHODS: A parallel serologic study was carried out with IgM and IgA enzymoimmunoassay enhancement techniques in the sera of patients suspected of having toxoplasmosis. RESULTS: Positive results for IgM and/or IgA were presented in 74 sera (47 patients): 86.3% for the former and 58.9% for the latter (p < 0.001). The group of IgA-/IgA+ sera presented a low mean of proportionality index (PI): 1.6 versus the IgM+ sera group in the context of IgG seroconversion with a PI of 3.4 (p < 0.001). Out of the 9 patients with demonstrated IgG, all were IgA+ and seven IgM+. CONCLUSIONS: The present data seem to support greater specificity of the determination of IgA antibodies than that of IgM in the diagnosis of acute toxoplasmosis. PMID- 7865559 TI - [Invasive infections caused by Streptococcus pyogenes. Changes in their clinical characteristics, new physiopathologic aspects, and current therapeutic approach]. PMID- 7865560 TI - [Atlanto-axial luxation secondary to cervical vertebral abscess]. PMID- 7865561 TI - [Pulmonary aspergillosis diagnosed with blood culture]. PMID- 7865562 TI - [Necrotizing vasculitis as cutaneous manifestation of brucellosis]. PMID- 7865563 TI - [A case of endocarditis caused by Clostridium entering through the gastrointestinal system]. PMID- 7865564 TI - [Mycoplasma pneumoniae pneumonia and myelitis]. PMID- 7865565 TI - [Reactive hemophagocytic syndrome with disseminated intravascular coagulation secondary to acute brucellosis]. PMID- 7865566 TI - [Fatal infection of odontogenic origin]. PMID- 7865567 TI - [Erythromycin-sensitive Streptococcus pyogenes]. PMID- 7865568 TI - [Transitory colonization by Scedosporium prolificans (inflatum) in a liver transplant recipient]. PMID- 7865569 TI - 39th Annual meeting of the GTH (Gesellschaft fur Thrombose- und Hamostaseforschung). Berlin, Germany, 15-18 February 1995. Abstracts. PMID- 7865570 TI - Abstracts of the International Symposium Acute Leucemias VI, Prognostic Factors and Treatment Strategies. Munster, Germany, 25 February-1 March 1995. PMID- 7865571 TI - Stable expression of the cDNA encoding the feline CD8 alpha gene. AB - The stable expression of the alpha chain of the feline cytotoxic T cell differentiation antigen (fCD8 alpha) on Crandell feline kidney cells (CRFK) was carried out by using an expression vector which contains the Rous sarcoma virus long terminal repeat and a neo resistant gene. After three rounds of cloning under G418 selection for over two months, the expression of the feline polypeptide was detected by human monoclonal antibody OKT8. PMID- 7865572 TI - Wasting condition under normal cardiac rhythms in rabbits following Strongyloides papillosus infection. AB - Pathogenicity of Strongyloides papillosus to rabbits was investigated by monitoring of food intake, body weight and electrocardiogram. No abnormalities were observed in rabbits infected with 10(4) infective larvae (L3)/kg. Rabbits given 10(5) L3/kg exhibited anorexia after the establishment of patent infections. Four of them died on Days 19-33 having lost 32-44% of initial body weight. The other one animal regained appetite and body weight as fecal egg output decreased. Cardiac rhythms remained normal even in the emaciation state. In lethal cases, cardiac activities finally disappeared through escape beats preceded by sinus arrhythmia as in a fasted control. These results suggest that heavy S. papillosus infection produces a wasting condition in rabbits resulting from anorexia under normal cardiac functions. PMID- 7865573 TI - Antagonistic effects of antipamezole on medetomidine-midazolam induced sedation in dogs. AB - Antagonistic effect of atipamezole (80 micrograms/kg) on medetomidine (20 micrograms/kg)-midazolam (0.3 mg/kg) induced sedation was evaluated in dogs. Atipamezole effectively reversed sedation and significantly shortened arousal time and total recovery time without apparent side effects. Atipamezole also effectively reversed changes in heart rate, respiratory rate and body temperature produced by medetomidine-midazolam. The possible use of atipamezole as a reversal agent might enhance the value and availability of medetomidine-midazolam for a chemical restraint agent in dogs. PMID- 7865574 TI - In vivo and in vitro transcription of small mRNAs containing a leader sequence from mouse hepatitis virus strain JHM. AB - Two additional small RNAs, named mRNA8 and 9, are transcribed from mouse hepatitis virus (MHV) in virus-infected mouse DBT cells. This report shows that the small mRNAs (mRNA8 and 9) were observed at 3 hr post infection (p.i.) in DBT cells infected with the JHM strain of MHV. This result suggested that products from mRNA8 and 9 may play a role in the early stage of the viral replication cycle in the infected DBT cells. The mRNA8 is initiated from a perfectly conserved intergenic site, but mRNA9 is from an imperfectly conserved intergenic sequence. Since mRNA8 and 9 were found in the liver and brain of an infected mouse, it was suggested that the imperfect intergenic sequence of MHV may serve as an initiation site for leader-primed transcription in vivo. PMID- 7865575 TI - Characterization of Haemophilus paragallinarum isolated in the Philippines. AB - In 1989 and 1990, we isolated five strains of Haemophilus paragallinarum in the Philippines. Serological studies were done on three of these isolates. The results of haemagglutination, reactability to monoclonal antibodies and cross immunization with standard strains showed that they belonged to serotypes A, B and C respectively. This is the first report on the isolation of H. paragallinarum and on a related serological study in the Philippines. PMID- 7865576 TI - Cross reactivity of serum antibodies from chickens immunized with three Eimerian species. AB - Cross reactivity of serum antibodies from chicken immunized with E. tenella, E. necatrix and E. acervulina was observed. The enzyme linked immunosorbent assay (ELISA) using soluble antigen prepared from oocysts of each species showed the cross reactivity among chicken serum immunized with the three species of protozoa, especially between E. tenella and E. necatrix. In immunoblot analysis with E. tenella oocyst antigen, 7 major bands were detected by homologous E. tenella antiserum and 10 and 6 bands were reacted by E. necatrix and E. acervulina antiserum respectively. In these antigens, the band of 33 kDa was regarded as cross reactive agent between E. tenella and E. necatrix because of high reactivity to both of the antiserum. In addition, the 130 kDa antigen that reacted with every antiserum was regarded as common antigen among these three species. PMID- 7865577 TI - Protein analysis of Anaplasma marginale and Anaplasma centrale by two-dimensional polyacrylamide gel electrophoresis. AB - Protein compositions of Anaplasma marginale and A. centrale were analyzed by two dimensional gel electrophoresis. Both species had a major protein which was composed of 3-4 spots. The molecular weights of these two proteins were approximately 39 kDa. However, the position of these proteins in the gels were slightly different when 2 gel maps were superimposed. Five other protein spots were shared by A. marginale and A. centrale, whereas all the other protein spots were appeared to be unique to each of the species. PMID- 7865578 TI - Application of oriented poly-L-lactide screws for experimental Salter-Harris type 4 fracture in distal femoral condyle of the dog. AB - The clinical usefulness of biodegradable oriented poly-L-lactide (PLLA) screws for experimental Salter-Harris type 4 fracture in the distal femoral condyle of dogs was evaluated. Bony union of the osteotomized fragment of the condyle was almost completed radiographically and histologically within 1 to 2 months after surgery, suggesting that PLLA screws maintained strength long enough to fix the fragment until bone healing. At 4 to 6 months after surgery, minute fissures were histologically confirmed on the surface of the screw thread, suggesting the early stage of biodegradation and absorption of the polymer. During the observational period, no significant difference between the treated femur and the contralateral non-treated femur in either total femoral length or maximum condyle width was observed, indicating no growth disturbance in the treated femur. From these results it was concluded that the PLLA screw might be an ideal implant for the reduction and fixation of epiphyseal plate fractures such as Salter-Harris type 3 or type 4 fractures. PMID- 7865579 TI - Expression and purification of recombinant Marek's disease virus serotype 1 specific phosphorylated protein pp38 in E. coli. AB - Phosphorylated protein pp38 is the only protein that is detected in the Marek's disease (MD) lymphoma caused by MD virus serotype 1 (MDV-1) and lymphoblastoid cell lines. In this study, a recombinant protein coded for by the almost entire open reading frame of the MDV-1 pp38 cDNA was produced in E. coli and purified by affinity chromatography. Prior to the expression and purification of the protein, cDNA containing the entire coding region for pp38 was cloned and its nucleotide sequence was determined. Immunoblot analysis indicated that the expressed recombinant protein electrophoresed close to that of the pp38 in infected cells. The difference in mobility of the purified recombinant and the pp38 in infected cells corresponded to a fusion peptide. The recombinant pp38 may be of interest for function analyses and the diagnotic use of pp38. PMID- 7865580 TI - Characterization of monoclonal antibodies against sporadic bovine leukosis cell lines. AB - We report here distributions of antigens expressed on sporadic bovine leukosis (SBL) cells by a total of 38 monoclonal antibodies (mAbs) directed against three different types of SBL-cell lines, BLT2 (thymic type), BTL-PC3 (calf type) and BLS1 (skin type). Most mAbs had high reactivities with some bovine lymphoma cell lines and less reactivity with normal lymphocytes except for some peripheral blood mononuclear cells (PBM) in cattle and certain other species. They were more reactive with cultured T-cell line BTL-PC3 and B-cell lines, BL312 and KU-1, than naturally occurring lymphoid tumor cells. Among the 38 mAbs, 27 was determined the molecular weights of their recognized antigens in Western blot analyses. A mAb C419 had high reactivity with lymphoma cell lines but no reactivity with normal lymphocytes, indicating that it recognizes tumor-associated antigens of SBL. PMID- 7865581 TI - Seasonal changes in spermatogenesis and ultrastructure of developing spermatids in the Japanese rat snake, Elaphe climacophora. AB - Seasonal changes in spermatogenesis and the ultrastructure of developing spermatids in the Japanese rat snake, Elaphe climacophora, were observed by light and transmission electron microscopy. Spermatogenesis in this species began in August, continued through October and ceased in November. No spermatozoa were found during other periods. Japanese rat snakes mate from May to July, and spermatogenesis occurs after the mating season. Therefore, according to Girons' classification (1982), the reproduction of this species was classified as a postnuptial type. Although the morphological changes in developing spermatids during spermiogenesis in these snakes fundamentally resembled those in mammals, some unique features were detected. The most prominent characteristic of the developing spermatids was lipid-like structures. These structures first appeared in early round spermatids, gradually increased in size and number, and, finally, aligned around the nucleus of mature spermatids. Although spermatozoa with lipid like structures were released from the epithelium, stored spermatozoa in vas deferenses had none of these structures. Lipid-like structures that apparently separated from spermatozoa were scattered in the vas deferens. Prominent elongation of mitochondria was also remarkable in elongated spermatids. PMID- 7865582 TI - Alteration of ganglioside composition in the erythrocytes associated with Theileria sergenti infection. AB - The changes in ganglioside composition of bovine erythrocytes associated with Theileria sergenti infection were investigated using the erythrocytes before and after the infection. The erythrocytes before infection with T. sergenti had GM3, sialosylparagloboside (SPG), i-active, and I-active ganglioside as predominant gangliosides. After infection with T. sergenti merozoites, the contents of SPG and i-active ganglioside were slightly less, and I-active ganglioside content was much less in the erythrocytes, though GM3 content did not so vary. The decreased I-active ganglioside content showed a recovery as the parasitemia waned to low level in the infected cattle. The total amount of lipid-bound sialic acid also decreased in the erythrocytes after the infection. Similar changes were also caused by the incubation of liposomes containing ganglioside fraction obtained from bovine erythrocytes with T. sergenti piroplasms. These results suggest that the reduction of the contents of SPG, i-active, and I-active ganglioside on the erythrocytes was related to the T. sergenti infection. PMID- 7865583 TI - Circadian variation of urinary enzymes in the dog. AB - Circadian variations of N-acetyl-beta-D-glucosamidase (NAG, EC 3.2.1.30) and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2) were examined in dogs. Urine and blood were collected at 4-hr intervals from adult mongrel dogs (11 males, 11 females) weighing between 7 and 13 kg. The collected urine and blood were used to measure creatinine, NAG and gamma-GTP. The amount of urine was significantly higher (p < 0.05) during the period from 12:00 to 16:00. Creatinine clearance did not show any characteristic variations and creatinine excretion was significantly higher (p < 0.05) during the period from 8:00 to 16:00. No characteristic variations were observed in the amounts excreted, activity, or NAG and gamma-GTP creatinine index. There were high correlations between creatinine excretion and creatinine clearance (r = 0.693), gamma-GTP excretion and gamma-GTP creatinine index (r = 0.724), NAG excretion and NAG creatinine index (r = 0.878), and between the NAG and gamma-GTP creatinine index of each 4-hr specimen and the NAG and gamma-GTP excretion of the 24-hr specimens. These results suggest the diagnostic usefulness measuring enzyme activity in non-periodically collected urine. PMID- 7865584 TI - An osteometrical study of the cranium and mandible of Ryukyu wild pig in Iriomote island. AB - We measured crania and mandibles of Ryuku wild pigs from Iriomote Island. Sex and age were determined by observation of lower teeth. From the present data, the growth pattern was established for some items. For several parts of the cranium and mandible, the relative growth coefficient was compared. The results obtained here are summarized as follows: (1) Although sexual dimorphism was already shown in the younger group, a significant difference in profile length and length from the angle was not seen in the adult group. (2) As the animal grew, the proportion of length to width became larger in the skull. (3) The visceral cranium grew more rapidly in length than the cerebral cranium. On the other hand, growth of the cerebral cranium contributed to width in cranial development. (4) The body of the mandible was shown to grow more rapidly in length than the ramus of the mandible. (5) The growth pattern of some items was related to that of their associated muscles. These basic data are expected to be compared with data from other population of the same subspecies and Japanese wild pig. The comparisons will contribute to the establishment of origin and phylogeny of this animal. PMID- 7865585 TI - Blood gas analysis in dogs with heartworm caval syndrome. AB - Blood gases and cardiopulmonary function were analyzed in 67 dogs with heartworm (HW) caval syndrome (CS) and 19 HW-free dogs. Arterial oxygen tension (PaO2) was 91.5 +/- 7.3 mmHg in the HW-free dogs, 74.9 +/- 14.3 mmHg in 46 dogs that subsequently survived surgical HW removal (surviving dogs) and 64.6 +/- 14.7 mmHg in 21 dogs which later died or were euthanatized following surgical treatment (nonsurviving dogs). PaO2 levels less than 60 mmHg were detected in 30.4% and 38.1% dogs in the surviving and nonsurviving groups, respectively. Arterial carbon dioxide tension (PaCO2) was 35.8 +/- 4.9 mmHg in the HW-free dogs, 30.7 +/ 5.6 mmHg in the surviving dogs, and 28.8 +/- 6.2 mmHg in nonsurviving dogs. PaO2 (p < 0.01) and PaCO2 were lower (p < 0.01) and the alveolar-arterial oxygen difference (AaDO2) was higher (p < 0.01) in CS dogs than in HW-free dogs. PaO2 was lower (p < 0.01) and AaDO2 was larger (p < 0.01) in the nonsurviving dogs than in the surviving dogs. Arterial blood pH and bicarbonate concentration were lower (p < 0.01) and the anion gap was larger (p < 0.01) in CS dogs than in the HW-free dogs. Serum lactic acid level in nonsurviving dogs (13.2 +/- 3.9 mmol/l) was higher (p < 0.01) than in the HW-free (1.7 +/- 0.8 mmol/l) and surviving dogs (2.7 +/- 1.8 mmol/l). The PaO2 correlated significantly with mean pulmonary arterial pressure (r = -0.65, p < 0.01), cardiac index (r = 0.44, p < 0.05) and total pulmonary resistance (r = -0.70, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865586 TI - Methemoglobin formation and reduction in canine erythrocytes characterized by inherited high Na+, K(+)-ATPase activity with normal and high glutathione concentrations. AB - The methemoglobin formation and methemoglobin reduction in canine erythrocytes characterized by inherited high potassium (K+) and normal reduced glutathione concentrations (HK-low GSH cells) were compared with those in canine erythrocytes with inherited high K+ and high GSH concentrations (HK-high GSH cells) and normal canine erythrocytes with low K+ and low (= normal) GSH concentrations (LK-low GSH cells). The rate of methemoglobin formation induced by sodium nitrite (NaNO2) was in the order; LK-low GSH > HK-low GSH > HK-high GSH cells, and the difference among groups was significant at 7 and 15 min. Methemoglobin reduction in a medium containing glucose occurred rapidly in both HK-high GSH and HK-low GSH cells, and the rate of reduction was 1.7-fold higher than in LK-low GSH cells. Accumulation of pyruvate equivalent to the amount of methemoglobin reduced indicated that methemoglobin was predominantly reduced by NADH-methemoglobin reductase coupled to glycolysis. HK-low GSH cells showed an increased glycolytic rate and high pyruvate kinase activity similar to the levels in HK-high GSH cells. It is therefore evident that HK-low GSH cells offer greater protection against oxidation of hemoglobin to methemoglobin than LK-low GSH cells because of the increased glycolytic rate in HK-low GSH cells attributable to high pyruvate kinase activity in these cells. PMID- 7865587 TI - Apoptotic changes in the thymus of mice infected with mouse hepatitis virus, MHV 2. AB - In mice infected with MHV-2, histopathological changes of the thymus was studied. Extensive cell lysis with pyknotic nuclear debris appeared at 48 hr postinfection, and cortico-medullary border was indistinguishable. Electron microscopy revealed vacuolation and shrinkage of the cytoplasm of lymphoid cells, margination of nuclear chromatin, and fragmentation of nuclei. Virus particles were detectable in the lymphoid and reticular epithelial cells, being immunohistochemically positive for viral antigen. By DNA electrophoresis thymocytes showed DNA fragmentation with a laddering pattern characteristic of apoptosis. PMID- 7865588 TI - Inheritance of immunoglobulin subclass regulator-1 (Igsr-1) in LEC mutant rats. AB - Long-Evans Cinnamon (LEC) mutant rats were reported to exhibit a deficiency in the serum immunoglobulin (Ig) G1. The phenotype determining the basal level of IgG1 was tentatively designated as immunoglobulin subclass regulator-1 (Igsr-1), and normal rats and LEC rats were categorized into Igsr-1A (normal expression of IgG1) and Igsr-1B (low expression of IgG1), respectively. In this report we examined genetic trait of this phenotype in LEC rats. The serum IgG1 levels in F1 hybrids produced by mating LEC rats (Igsr-1B) with normal rats (Igsr-1A) were intermediate level, indicating that Igsr-1 behaves as a co-dominant genetic trait. When backcross rats were examined, serum IgG1 levels varied between those in normal and LEC rats without clear segregation, indicating that Igsr-1 is controlled by multiple genes. Furthermore, the serum IgG1 level in each backcross rat did not correlate to another recessive mutant genotype, thid (T-helper immunodeficiency). These data suggest that the deficiency in serum IgG in LEC rats is independent of the deficiency in helper T cell function, but might be due to the multiple deficiency in as-yet-unidentified mechanisms. PMID- 7865589 TI - Application of DNA fingerprinting in the Hokkaido brown bear (Ursus arctos yesoensis). AB - DNA fingerprinting employing a minisatellite Myo probe was used for individual identification and paternity determination in Hokkaido brown bears (Ursus arctos yesoensis). We used two restriction enzymes, HinfI and HaeIII to make DNA fingerprints. Band patterns obtained from randomly selected bears were compared with each other, and the probability x that fragment in an individual was also present in the other was 0.69 for HinfI and 0.83 for HaeIII. The value for HinfI (0.69) was similar to that obtained from other species, such as dog and domestic animals, and the mean probability of all fragments was calculated to be 2.5 x 10( 2). The results suggest that DNA fingerprinting applying the combination of HinfI and Myo is available for individual identification. On the other hand, the ability to determine paternity seemed to be insufficient owing to the lack of paternal fragments, although the band patterns reflected the correct relationships between child and father. PMID- 7865590 TI - Isolation and serological characterization of porcine reproductive and respiratory syndrome (PRRS) viruses from pigs with reproductive and respiratory disorders in Japan. AB - Three porcine reproductive and respiratory syndrome viruses (PRRSVs) were successfully isolated from stillborn piglets and fattening pigs derived from different herds affected either with an epizootic reproductive failure or a severe chronic respiratory distress in Japan. The isolates were reacted with antisera against both European (Lelystad virus) and American (strain 46448) PRRSVs in indirect immunofluorescence (IIF). However, cross immunoperoxidase monolayer assay revealed the close serological relationships between the Japanese isolates and American PRRSV, but not between the Japanese isolates and the European PRRSV. The data of preliminary serological survey with IIF technique showed a high frequency of antibody positive pigs against both Japanese isolate and the American PRRSV, whereas a low frequency of antibody positive pigs against the European PRRSV, on herds which have had clinical episodes of PRRS-like diseases. These results indicate that PRRSVs are prevalent in Japan, and suggest that the antigenicities of the prevalent PRRSVs are more closely related to those of the American than the European PRRSVs. PMID- 7865591 TI - Comparative functional analysis of the various lentivirus long terminal repeats in human colon carcinoma cell line (SW480 cells) and feline renal cell line (CRFK cells). AB - Basal promoter activities of various lentiviral long terminal repeats (LTRs) in a human colon carcinoma cell line (SW480 cells) and a feline renal cell line (CRFK cells) were examined by the chloramphenicol acetyltransferase (CAT) assay using the LTR-CAT reporter plasmids. In SW480 cells, the basal promoter activities induced by LTRs of visna virus, caprine arthritis-encephalitis virus (CAEV), and simian immunodeficiency virus (SIVAGM) were moderate, and those induced by LTRs of human immunodeficiency virus (HIV) type 1 (HIV-1) and HIV type 2 (HIV-2) were low. However, the activity induced by the LTR of feline immunodeficiency virus (FIV) was extremely low. In CRFK cells, the basal promoter activities induced by LTRs of visna virus, CAEV and SIVAGM were relatively high, and those induced by LTRs of HIV-1, HIV-2 and FIV were moderate. From these data, although the structure of the LTR of FIV is reported to be similar to that of visna virus and CAEV, the function of the LTR of FIV is rather quite different from that of the LTR of these viruses. PMID- 7865592 TI - An outbreak of porcine reproductive and respiratory syndrome in Japan. AB - An emerging swine disease principally involving periweaning piglets was examined. The disease was clinically characterized by lethargy, fever, emaciation, coughing, and severe abdominal breathing, hence colloquially named "Heko-heko" disease. The consistent lesions in affected piglets were diffuse interstitial pneumonia with pronounced type II pneumocytic proliferation, meningoencephalitis, and regression of the lymphoid tissues. The causal virus was isolated in primary porcine lung cell (PLC) cultures from various organs of affected piglets and showed serological relatedness to the European porcine reproductive and respiratory syndrome (PRRS) virus. Numerous virus particles, measured about 49 nm in diameter, were detected in the cytoplasm of alveolar epithelial cells and pulmonary macrophages in PLC cultures infected with the isolate. The condition could be experimentally reproduced in conventional piglets by intranasal inoculation with the isolate and the virus was reisolated from the infected animals. PMID- 7865593 TI - Immunohistochemical colocalization of serotonin, aromatic L-amino acid decarboxylase and polypeptide hormones in islet A- and PP-cells of the cat pancreas. AB - To establish which monoamines are elaborated in the pancreatic islet cells of cats, the pancreatic tissue was studied by immunohistochemistry on serial or mirror tissue sections. Glucagon-containing A-cells reacted immunohistochemically with antisera directed against serotonin and aromatic L-amino acid decarboxylase, though the half of A-cells immunostained with glucagon antiserum did not show the colocalization with serotonin. Pancreatic polypeptide-containing PP-cells also showed immunoreactivity for antisera directed against serotonin and aromatic L amino acid decarboxylase. However, PP-cells exhibiting immunoreactivity for serotonin were very few in number. The overlapping areas of the two types of cell represented only a small proportion of the PP-cells. Immunoreactivity for aromatic L-amino acid decarboxylase was observed within almost all A- and PP cells. Since aromatic L-amino acid decarboxylase is an enzyme involved in the synthesis of serotonin, it is concluded that pancreatic islet A- and PP-cells in cats have the ability to elaborate serotonin. Contrarily, islet B- and D-cells showing immunoreactivity for insulin and somatostatin antisera, respectively, did not react with antisera directed against serotonin and aromatic L-amino acid decarboxylase. PMID- 7865594 TI - Antibacterial activity of tilmicosin against Pasteurella multocida and Actinobacillus pleuropneumoniae isolated from pneumonic lesions in swine. AB - Sixty one strains of Pasteurella multocida and 35 strains of Actinobacillus pleuropneumoniae isolated from pneumonic lesions of porcine lungs during the period from 1985 to 1989 in Japan were tested for antibiotic susceptibility to chlortetracycline (CTC), thiamphenicol (TP), tylosin (TS), acetylisovaleryl tylosin (AIV-TS), tilmicosin (TMS), mirosamycin (MRM). Most strains of both species were sensitive to CTC, TP and TMS. Growth of fifty-one strains (83.6%) and forty-six strains (75.4%) of P. multocida were inhibited with 3.13 micrograms/ml of CTC and 0.78 micrograms/ml of TP, respectively. TS showed low activity against almost all strains (MIC > or = 6.25 micrograms/ml). Fifty-eight (95.1%), twenty-three (37.7%) and fifty (82%) of P. multocida showed MICs of > or = 6.25 micrograms/ml against AIV-TS, TMS and MRM, respectively. The MICs of A. pleuropneumoniae against CTC were less than 1.56 micrograms/ml. Thirty-two strains (91.4%) and 33 strains (94.3%) of A. pleuropneumoniae were inhibited with 3.13 micrograms/ml of TP and TMS respectively. However, TS, AIV-TS and MRM showed low activity against all of A. pleuropneumoniae (MIC > or = 6.25 micrograms/ml). Three different resistance patterns were observed in P. multocida and two in A. pleuropneumoniae isolates, respectively. PMID- 7865595 TI - Cardiovascular effects of dibutyryl cyclic AMP and milrinone under right heart bypass in anesthetized dogs. AB - To compare the cardiovascular effects of dibutyryl cyclic AMP (DBcAMP) and milrinone, we used the right heart bypass method in intact anesthetized dogs. The preload of the left ventricle was maintained constant throughout the experiment. Therefore, the effects of DBcAMP and milrinone on cardiac contractility and afterload of the left ventricle were investigated respectively without preload influence. DBcAMP and milrinone exhibited marked positive chronotropic-, positive inotropic-, vasodilative- and diuretic-activity. DBcAMP expressed these effects gradually and continuously, whereas milrinone expressed its pharmacological actions rapidly, but for a short duration of time. Both the afterload-reducing and the cardiac contractile force-enhancing activities of DBcAMP were longer lasting than those of milrinone. Mean arterial pressure was not altered by DBcAMP infusion, whereas it was increased significantly (p < 0.05) by milrinone infusion. The results of this study suggested that DBcAMP appeared to be indicated when there is a need to increase cardiac output by reducing afterload and increasing cardiac contractile force gradually and continuously. On the other hand, milrinone would seem to be indicated when the goal is to raise blood pressure rapidly and to increase cardiac output simultaneously. PMID- 7865596 TI - Seroepidemiological studies of bovine babesiosis caused by Babesia ovata, B. bigemina and B. bovis in Peninsular Malaysia. AB - Cattle in Peninsular Malaysia were examined for evidence of infection with Babesia ovata, B. bigemina and B. bovis by an enzyme-linked immunosorbent assay for detection of antibody to the three Babesia species. All of the test samples when assayed with B. ovata antigen, resulted in low value indicating low probability of cattle infected with B. bigemina, 74.4% were positive for B. bovis and 72.6% were positive for both Babesia species. In addition, a serological survey with regard to age difference was carried out on a milk production farm. High reactivity antibody to B. bigemina and B. bovis was detected in calves less than 1 month of the age. The reactivity decreased in calves 1-3 months of the age. Then, the reactivity increased for both Babesia species in 6 months old calves. These results suggested that cattle infected with B. bigemina and B. bovis were widespread throughout Peninsular Malaysia and that both parasites might exist as an enzootical parasite. PMID- 7865597 TI - Magnetic resonance imaging of young and aged rat brains under a magnetic field of 7.05 T. AB - Using a homemade MR imaging probe (Helmoholtz coil), MR images of brains of 5 week-old and 23- or 24-month-old Wistar rats were taken under a magnetic field of 7.05 T (Tesla). The probe was designed to fit the rat head and made by winding thin copper film round an acrylic tube with a 5-cm i.d., 10-cm length and 2-mm thickness. This was adjusted to resonate with the 300 MHz radiofrequency corresponding to the resonance frequency of 1H under a magnetic field of 7.05 T. MR images were obtained by T1-weighted and two-dimensional Fourier transformation techniques. The sagittal and coronal sections were imaged in 1-mm-thick slices. The size of the data matrix was 128 phase-encoded steps. Each image was obtained through eight acquisitions. A comparison of the MR images with those semi microscopically taken at the same position of the coronal section revealed that the cerebral cortex, hippocampus, hypothalamus and thalamus were clearly imaged by this probe. With aging, MR images of cerebral cortices were observed with decreased signal intensities. Enlargement of the third ventricles and hypertrophy of cranical parietal bones were also recognized in sagittal MR images of aged rats. These observations were more marked in males than in females. From these observations it was concluded that this probe was applicable for MR imaging of rat brains under a magnetic field of 7.05 T. PMID- 7865598 TI - Comparison of sedative effects induced by medetomidine, medetomidine-midazolam and medetomidine-butorphanol in dogs. AB - Sedative effects of combinations of medetomidine at 20 micrograms/kg--midazolam at 0.3 mg/kg (Me-Mi) and medetomidine at 20 micrograms/kg--butorphanol at 0.1 mg/kg (Me-B) were evaluated comparing with those of medetomidine alone (20, 40 and 80 mu/kg). All dogs given Me-Mi or Me-B were smoothly and rapidly induced to more profound and longer sedation than those by medetomidine alone. Especially, Me-Mi produced desirable sedation with moderate reflex depression, analgesia, excellent muscle relaxation and immobilization without further side effects. This potent effect of this combination seemed to be induced by a synergistic interaction between medetomidine and midazolam. This combination is available and valuable as a chemical restraint agent in dogs for various diagnostic or therapeutic procedures accompanied by light pain. PMID- 7865599 TI - Monoclonal antibody S37 induces apoptosis in bovine T lymphoma cells. AB - Influences of 38 monoclonal antibodies (mAbs) on the growth of bovine T lymphoma cells (BTL-27) were examined. One of them, S37, inhibited the cell growth strikingly when it was added to the cultures. S37-treated cells showed DNA fragmentation containing approximately 200-base pair multiple patterns and chromatin condensation. This evidence suggested that mAb S37 induced apoptosis in BTL-27 cells. PMID- 7865600 TI - Comparative analysis of the 5' non-coding region of pestivirus RNA detected from live virus vaccines. AB - Comparative analysis of nucleotide sequences in the 5' non-coding region (NCR) of pestivirus RNA detected from live porcine and human virus vaccines indicated that the contaminants are of bovine viral diarrhea virus (BVDV), and that there are at least three genotypes, which are distinct from hog cholera virus, among the BVDV strains. Most of the nucleotide changes in variable regions of the 5' NCR were covariant, with complementary substitutions at other positions for secondary structures. The proposed secondary structure in the 5' NCR was similar to the prokaryotic rho independent terminator. Short open reading frames in the 5' NCR were well conserved among pestiviruses. PMID- 7865601 TI - Relationships between the number of small follicles prior to superovulatory treatment and superovulatory response in Holstein cows. AB - In order to determine relationships between the number of small follicles prior to superovulatory treatment and superovulatory response, a total of 55 superovulations were induced in Holstein cows. The ovaries were examined ultrasonographically once 0-1.5 days before the initiation of superovulatory treatment. The number of small follicles 3-6 mm in diameter on both ovaries before superovulatory treatment was found to be significantly correlated with the numbers of corpora lutea after superovulation (r = 0.440, P < 0.001), total ova recovered (r = 0.503, P < 0.001) and transferable embryos recovered (r = 0.482, P < 0.001). These results indicate that a single ultrasonographic examination of follicles 3-6 mm in diameter prior to superovulatory treatment can be utilized to predict superovulatory response. PMID- 7865602 TI - Crossed fat embolism in a cow with tetralogy of Fallot. AB - A 10-month-old, female Holstein-Friesian cow with tetralogy of Fallot died during surgery for ameliorating pulmonary stenosis. Necropsy revealed no fracture of bones. Microscopically, fat emboli in the capillaries were detected in the brain, kidney, lung, adrenal gland and pituitary. In the kidney, many fat emboli were present in the glomeruli. No significant changes of the neurons were found throughout the brain, and perivascular hemorrhage and/or necrosis were rarely seen accompanying with fat emboli in the cerebral cortex. The trigger for fat embolism might be costectomy, and right-to-left shunt due to heart malformation might be attributed to crossed and systemic distribution of the fat emboli. PMID- 7865603 TI - Prevalence of valvular regurgitation in normal beagle dogs detected by color Doppler echocardiography. AB - We examined the prevalence and characteristics of valvular regurgitation in 20 normal beagle dogs with no cardiac murmur by color Doppler echocardiography. The prevalence of pulmonary, mitral, aortic and tricuspid valvular regurgitation was 75%, 15%, 10%, and 0%, respectively. The peak flow velocity of pulmonary, mitral and aortic regurgitation was 57.1 +/- 18.5 cm/sec (mean +/- SD), 89.8 cm/sec (mean) and 96.5 cm/sec, respectively. The peak velocity of regurgitant flow was considered characteristically low, as the calculated pressure gradient derived from the modified Bernoulli equation (pressure gradient = 4 x velocity) was not as high as the normal pressure gradient existing across each valve. We consider that, in the evaluation of the characteristics of regurgitation in dogs, regurgitant signals having low peak velocity can be regarded as being physiological or trivial regurgitation. PMID- 7865604 TI - Infectivity of three species of Fasciola to Wistar rats. AB - The infectivity of Fasciola spp. to Wistar rats was evaluated with the recovery rate and development of flukes. The recovery rate from the liver parenchyma and bile duct was 20.0-30.0% in F. hepatica, 36.6-47.5% in Japanese Fasciola sp. and 0-5.0% in F. gigantica. Mature flukes were first recovered at week 8 in F. hepatica and week 12 in Japanese Fasciola sp., however, F. gigantica did not mature in the rats examined until 12 weeks after infection. These results suggest that F. hepatica and Japanese Fasciola sp. are high in infectivity to Wistar rats, whereas F. gigantica is low. PMID- 7865605 TI - A case report of surgical treatment of a dog with atrioventricular septal defect (incomplete form of endocardial cushion defect). AB - A 3-month-old female collie was diagnosed as having atrioventricular septal defect with ostium primum atrial septal defect (PASD). The diagnosis was made by echocardiographic observation of the PASD and goose-neck deformity on left ventriculogram. The PASD was treated surgically with a patch graft under cross circulation cardiopulmonary bypass (CC). The PASD was identified above the ventricular septum after right atriotomy. The patch graft was sutured along the fibrous tissue of the tricuspid annulus on the ventricular side of the PASD to avoid injuring the conduction system. After the operation, cardiac function and renal output were well preserved, but the dog died 33 hr later. At postmortem examination, a mitral cleft was identified. PMID- 7865606 TI - The genotype of Aujeszky's disease viruses isolated in Argentina. AB - Genomes of four Argentine isolates of Aujeszky's disease virus (ADV) (Rio Cuarto/79, Mercedes, Chanar Ladeado-7 and Chanar Ladeado-15) from pigs were characterized and compared with four ADV strains obtained from U.S.A. (Indiana S), Sweden (Sweden 66), France (Alfort) and Japan (Yamagata-S81) by restriction endonuclease (RE) analysis. Although three Argentine isolates were classified into type I of BamHI cleavage pattern, one isolate, Mercedes, belonged to type II, according to the classification by Herrmann et al. [6]. Since this type II virus was first isolated in 1981, no outbreak of ADV infection by this type has so far been reported in Argentina. This may imply that the immediate measures by total slaughter of pigs in the farm led successful eradication of the type II ADV infection in Argentina. This report is the first epidemiological study using RE analysis on ADV strains in this country. PMID- 7865607 TI - A case of intracytoplasmic edema of follicular epithelial cells in rat thyroid. AB - Hydropic change of follicular epithelial cells in the thyroid was observed in a female Fischer 344 rat. Microscopically follicular epithelial cells were characterized by edematous swelling with weakly eosinophilic and homogeneous cytoplasm. The cytoplasm was negative for periodic acid-Schiff reaction, and thyroxine- and thyroglobulin-immunohistochemical reactions. Electron microscopically, a small amount of amorphous substance was noted in remarkably dilated rough-surfaced endoplasmic reticulum (r-ER), and slight regressive changes of cytoplasmic organella were also observed. These morphological changes may indicate that focal intracytoplasmic edema was occurred in r-ER, and that the change belonged to hydropic degeneration of the thyroid follicular cells in the thyroid. PMID- 7865608 TI - Muscular dystrophy of the diaphragmatic muscles in Holstein-Friesian cows. AB - Six Holstein-Friesian cows suffering from recurrent rumenal tympany were pathologically investigated. Macroscopical lesions associated with the clinical symptoms were confined to the diaphragmatic muscles which were pale, and stiff on palpation. Histopathological examination revealed various degenerative changes in diaphragmatic muscles as follows: variation in muscle fiber diameter, vacuolar and hyalinized degeneration of muscle fibers, fiber splitting, central core-like structures, sarcoplasmic masses and ring fibers. These characteristic features in the present cases were consistent with dystrophy of the diaphragmatic muscles in Meuse-Rhine-Yssel cattle. From these observations, it is confirmed that muscular dystrophy of the diaphragmatic muscles dose occur in Holstein-Friesian cows, although a genetic mode was not proven. PMID- 7865609 TI - Response of sows to estradiol benzoate after weaning. AB - Estradiol benzoate (E2B) was intramuscularly injected in 3 groups of weaned sows at a dose of 0.2 mg/head on day 0 and on day 2 and at a dose of 0.4 mg/head on day 2, respectively. The blood concentration of LH rose to a peak 60-66 hr after E2B injection. The rates of the occurrence of estrus after E2B treatment in these groups were 85.7, 89.5 and 87.5%, respectively, with no significant differences compared to the control except for the second group. The farrowing rates in the 3 treated groups were 100, 86.8 and 61.9%, respectively, and the value in the third group was significantly lower compared to the control (p < 0.05). There were no significant differences in average litter size between the control and any of the treated groups. PMID- 7865610 TI - Reactivity of serum anti-erythrocyte membrane antibody in Babesia gibsoni infected dogs. AB - Reactivity of anti-erythrocyte membrane (RBCm) antibody in sera of B. gibosni infected dogs on native RBCm and erythrocyte surface (RBCs) was examined using an enzyme linked immunosorbent assay. Anti-RBCm antibody attached to native RBCm and the surface of erythrocytes (RBC) treated with phenylhydrazine or neuraminidase, but not to the surface of non-treated RBC. Based on these results, anti cytoskeletal protein antibody in sera of B. gibsoni-infected dogs is considered to attach to native RBCm, and furthermore free radical-induced oxidative stress imposed on RBC and sialic acid removal from glycoproteins of RBC are considered necessary for anti-transmembrane protein antibody in sera of B. gibsoni-infected dogs to be bound to RBCs. These are important to elucidating the mechanism of the marked increase in RBCs-bound IgG value and anemia in B. gibsoni infection. PMID- 7865611 TI - Characterization and extracorporeal application of a new phosphate-binding agent. AB - A new phosphate-binding agent which does not cause any severe side effects in vivo was developed by modifying a crosslinked dextran with polynuclear iron(III)oxide-hydroxide. Its particle size ranges from 150 to 300 microns, and the iron content was about 18% by dry weight. The oxidation state of iron was characterized by ESCA and Mossbauer spectroscopy. The maximum phosphate binding capacity of the iron(III)oxide-hydroxide-modified dextran was determined with respect to aqueous phosphate solutions, human serum and whole blood. The effects on whole blood count, haemolysis, protein concentration and enzyme activities were examined. In addition, the influence of phosphate concentration, pH and temperature on the phosphate uptake of the material was determined. The results show that this new adsorbent might provide an alternative to conventional phosphate-binding agents. This paper also describes the first experiments on the therapeutic application of the material in an extracorporeal blood perfusion system for the treatment of hyperphosphataemia during haemodialysis. PMID- 7865612 TI - Ethanol induced oxidative stress and membrane injury in rat erythrocytes. AB - The aim of this study was to observe membrane injury and to investigate the mechanism of antioxidant defence systems against acute ethanol toxicity. Erythrocyte superoxide dismutase and Na+, K(+)-ATPase activities were significantly decreased and catalase levels were significantly increased one hour after ethanol intoxication of male swiss albino rats. These data demonstrated that superoxide dismutase and catalase are susceptible to lipid peroxidation and that these enzymes protect tissues from free radicals. The possible mechanism involved in Na+, K(+)-ATPase and Ca(2+)-ATPase inhibition are discussed in relation to the development of ethanol toxicity and the role of lipid peroxidative processes. PMID- 7865613 TI - Glucose intolerance in liver cirrhosis: role of hepatic and non-hepatic influences. AB - Oral glucose tolerance was tested in a heterogeneous group of 108 patients with liver cirrhosis. Data were compared with those from 181 subjects without liver disease (44% normal, 35% impaired glucose tolerance and 21% type 2 diabetes mellitus). In cirrhosis, 27% of the patients had normal, 36% had impaired glucose tolerance, and 37% were diabetic. There was no association between glucose intolerance or diabetes and the aetiology of cirrhosis, the duration of the disease, the biochemical indicators of hepatocyte damage, cholestasis and/or liver function. Only weak associations were found between the results of quantitative liver functions tests (caffeine, xylocaine, indocyanine green) and basal and post load glucose and insulin concentrations. Cirrhotics with 1st degree relatives with type 2 diabetes mellitus (n = 16) did not show an increased prevalence of diabetes. Older and/or malnourished patients were more frequently glucose intolerant. Using the plasma glucose concentration 120 minutes after glucose load as the dependent variable, multivariate regression analysis showed that 54% of its variance is associated with the following variables: basal plasma glucose (36%) and free fatty acid concentration (5%), age (3%), basal glucose oxidation rate (3%), muscle mass (3%) and plasma free glycerol at 120 minutes after glucose load (3%). By contrast, the clinical state of the patients (i.e. the CHILD-Pugh score) accounted for only 2% of the variance. We conclude that glucose tolerance is variable in cirrhosis. After manifestation of liver disease, glucose intolerance or diabetes cannot be explained by the clinical, histological or biochemical signs of liver disease. PMID- 7865614 TI - Flow injection determination of glutamate in human serum and rat brain samples with immobilized glutamate oxidase and glutamate dehydrogenase reactors. AB - Two methods are proposed for the determination of regional concentrations of glutamate in the rat brain as well as in human serum. Glutamate oxidase was immobilized on non-porous glass beads and glutamate dehydrogenase was immobilized on glass derivatives. These supports were employed for the construction of Single Bead String Reactors and Packed Bed Reactors, respectively, which in turn were linked to Flow Injection Analysis systems with either photometric or fluorometric detection. Analytical working curves are linear in the range 1-200 mumol/l for packed bed reactors and 10-500 mmol/l for single bead string reactors. The samples were pretreated depending on their origin and the applied measuring system. Optimal dilution factors were established for the two techniques. Optimal dilution ratios were established and the influence of several added substances was investigated. Recovery and method comparison studies including high performance liquid chromatography verified the accuracy of the proposed methods. Results from within-day and between-day measurements gave relative standard deviations of 4.7 and 5.9% for serum samples and 2.5 and 4.0% for brain samples, respectively. PMID- 7865615 TI - Transferability of lipase titrimetric assays: deductions from an interlaboratory study. AB - Following the selection of the most appropriate method for emulsification and the optimization of the reaction medium, interlaboratory studies were conducted to check the effect of preparing substrates and measuring the catalytic concentration of lipase at different sites as well as the effect of transport on emulsion. The determinations of lipase activity in an abnormal chemistry control against emulsions prepared by two laboratories (and used by both laboratories) and, also, against five separate emulsions prepared by one laboratory (and used by five different laboratories) resulted in average enzyme activity values (2234 +/- 125 and 2263 +/- 204 U/l respectively) which are not statistically different. Standard preparations of lipase, control sera and reference materials can therefore be titrated according to the procedure followed by at least two laboratories for at least 3 days against two separate emulsions. PMID- 7865616 TI - Tissue polypeptide antigen and tissue polypeptide specific antigen in primary breast cancer. Evaluation in serum and tumour tissue. AB - Tissue polypeptide antigen, measured by both a polyclonal antibody (TPA IRMA Prolifigen) and a monoclonal antibody prototype kit (TPA-M IRMA Prolifigen), and the tissue polypeptide specific antigen were evaluated. The markers were measured in 266 serum samples and in 291 tumour cytosols from patients with primary breast cancer. The three markers were available in matched pairs of both serum and cytosol from the same patient in 144 cases. Diagnostic sensitivity of serum levels of the three markers was not significantly different when using cut-off values calculated on the basis of healthy subjects. In the cytosol, tissue polypeptide antigen (TPA IRMA), tissue polypeptide antigen (TPA-M IRMA) and tissue polypeptide specific antigen were significantly correlated with steroid receptor status, while their serum levels were not. Cytosol and serum levels of the three markers were not significantly associated. All three were significantly correlated both in serum and in cytosol. The association was closer between tissue polypeptide antigen (TPA IRMA) and tissue polypeptide antigen (TPA-M IRMA) than between each of these two markers and tissue polypeptide specific antigen. From these findings we draw the following conclusions: 1. Tissue polypeptide specific antigen (TPA IRMA) and tissue polypeptide antigen (TPA-M IRMA) probably provide superimposable information both in serum and in cytosol; 2. Tissue polypeptide specific antigen and tissue polypeptide antigen (TPA IRMA) or tissue polypeptide antigen (TPA-M IRMA), although closely associated, probably measure in part different cytokeratins. Therefore, they should not be considered interchangeable in individual patients; 3. The determination of the markers in serum and in cytosol provides different information concerning the tumour phenotype. PMID- 7865617 TI - Generation of reference values for cardiac enzymes from hospital admission laboratory data. AB - An approach is described for using patient databases of a hospital information system as a source of reference values for cardiac enzymes. Of a total of 2029 emergency admission patients with serial cardiac enzyme data, 538 patients were considered "healthy" (having no damage in myocardium) because their discharge diagnoses suggested neither myocardial damage nor any other condition that could lead to elevated enzyme activities, and because their serially collected cardiac enzyme activities remained stable. Enzyme activities of creatine kinase (EC 2.7.3.2), creatine kinase isoenzyme MB, lactate dehydrogenase (EC 1.1.1.28), and lactate dehydrogenase isoenzyme 1 of these patients at admission to hospital were considered as suitable health related reference values. The upper (97.5%) reference limits of activities, measured at 37 degrees C according to Scandinavian recommendations, were as follows (age dependent limits given at 25 and at 75 years of age, U/l): creatine kinase men 268, 192; creatine kinase women 200 (no age effect); creatine kinase-MB 16, 24; lactate dehydrogenase 497, 603; lactate dehydrogenase isoenzyme 1 103, 140. For comparison, reference values were also produced conventionally from a group of 246 healthy subjects. Observed effects of age on enzyme activities were quite similar to those in the selected patient group. Calculated reference limits for isoenzymes creatine kinase-MB and lactate dehydrogenase isoenzyme 1 were also similar but reference limits for less cardiospecific total enzyme activities, creatine kinase and lactate dehydrogenase, were more variable between these two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865618 TI - Assay of endotoxin in human plasma using immobilized histidine, Limulus amoebocyte lysate and chromogenic substrate. AB - The Limulus amoebocyte lysate test for endotoxin is inhibited or enhanced by many substances. It is particularly difficult to determine endotoxin in plasma. In order to overcome this problem, we have modified the specific endotoxin assay method by using a membrane filter unit, a chromogenic Limulus amoebocyte lysate reagent, and immobilized histidine (which is a specific adsorbent for endotoxins). This immobilized histidine method consists of the endotoxin adsorption step on immobilized histidine, the separation step, in which Limulus amoebocyte lysate-interfering substances are removed, and the Limulus amoebocyte lysate test. Preheating of plasma samples (40-fold dilution with distilled water, at 100 degrees C for 7.5 min) was necessary, and it was necessary to dilute the sample more than 100-fold for the adsorption step. Under these conditions, the fraction of endotoxin recovered from plasma by the immobilized histidine method was almost 1. Moreover, by increasing the sample volume and extending the Limulus amoebocyte lysate reaction time, the sensitivity could be increased. By using the immobilized histidine method, 50-200 units/l of endotoxin in plasma samples can be accurately assayed. The method was used for the determination of plasma endotoxin in rabbits. PMID- 7865619 TI - Quantitative urinalysis with a common predilution on a DuPont Dimension. AB - Urine was quantitatively analysed for sodium, potassium, creatinine, calcium, urea, uric acid, inorganic phosphate and magnesium in one manual central predilution. The analysis was implemented on a DuPont Dimension and the results were compared with those obtained with our analysers currently in use. Based on modified serum methods and their assessed linearities, the 8 urine constituents were analysed with high accuracy and reproducibility in a 6-fold diluted urine with DuPont reagents. The Dimension method correlated well with flame photometry for sodium and potassium; with the EPOS analyser for creatinine, calcium, uric acid, urea and inorganic phosphate; with atomic absorption spectroscopy for magnesium. All between-run coefficients of variation were smaller than 5%, except for the analysis of sodium in the lower part of the measurement range. However, a dilution ratio of 6 is an acceptable compromise when these 8 constituents are determined collectively from a common predilution, thereby covering the complete measurement ranges for these analytes in urine specimens. An additional dilution step is necessary for only a few urine samples (fewer than 1% of samples for calcium and urea and fewer than than 2% for inorganic phosphate). The combined analysis of these 8 constituents can be carried out only on untreated urine samples. Currently recommended pretreatments, such as acidification for calcium and inorganic phosphate analysis, and uric acid analysis under alkaline conditions, can be avoided. PMID- 7865620 TI - Criteria for the selection of immunochemical measurement procedures. PMID- 7865621 TI - Lysosomes and human liver disease: a biochemical and immunohistochemical study of beta-hexosaminidase. AB - Liver biopsies from 88 patients with different liver diseases were studied for beta-hexosaminidase activity. Liver specimens with normal light microscopical morphology showed no immunohistochemical reactivity for beta-hexosaminidase. Increased reactions were noted, mainly in hepatocytes, in biopsies from the patients with different liver diseases. A very large interindividual variation of biochemical liver beta-hexosaminidase activity occurred even within the same diagnostic group, and no group of patients showed any significant increase of liver beta-hexosaminidase activity compared with the patients with normal liver histology. Livers with positive immunohistochemistry showed increased biochemical values for beta-hexosaminidase. In patients with cholestasis due to alcohol abuse, the immunohistochemical reaction was intense and the biochemical beta hexosaminidase activity was significantly increased compared with non-alcoholic cholestatic cases. Furthermore, blood samples taken from 50 patients at the same time as the liver biopsies. These patients showed significantly increased serum beta-hexosaminidase activity compared with normal controls, but no correlation was found between beta-hexosaminidase activities in the liver and serum of these patients. PMID- 7865622 TI - Posttranslational heterogeneity of bone alkaline phosphatase in metabolic bone disease. AB - Bone alkaline phosphatase is a marker of osteoblast activity. In order to study the posttranscriptional modification (glycosylation) of bone alkaline phosphatase in bone disease, we investigated the relationship between mass and catalytic activity of bone alkaline phosphatase in patients with osteoporosis and hyperthyroidism. Serum bone alkaline phosphatase activity was measured after lectin precipitation using the Iso-ALP test kit. Mass concentration of bone alkaline phosphatase was determined with an immunoradiometric assay (Tandem-R Ostase). In general, serum bone alkaline phosphatase mass and activity concentration correlated well. The activity : mass ratio of bone alkaline phosphatase was low in hyperthyroidism. Activation energy of the reaction catalysed by bone alkaline phosphatase was high in osteoporosis and in hyperthyroidism. Experiments with neuraminidase digestion further demonstrated that the thermodynamic heterogeneity of bone alkaline phosphatase can be explained by a different glycosylation of the enzyme. PMID- 7865623 TI - Coagulation factor XIII in plasma of patients with benign and malignant gynaecological tumours. AB - Fibrinogen and factor XIII were measured in sixty-four women with recently detected gynaecological tumours. Twenty-six of these tumours were benign and 32 were malignant: of the last group, nine patients had metastases. No patient showed clinical signs of bleeding or thrombosis. A reference group consisted of 31 age-matched healthy women. For fibrinogen, no significant deviation between the patient groups and the control group was found. The median values of factor XIII were higher in the benign tumour group than in the control group. In patients with a gynaecological tumour and metastases, factor XIII was significantly lower than in the non-metastasized malignancy group or in the benign tumour group. PMID- 7865624 TI - Neopterin production and tryptophan degradation in acute Lyme neuroborreliosis versus late Lyme encephalopathy. AB - Fourteen patients with Borrelia burgdorferi infection were investigated for possible abnormalities of tryptophan and neopterin metabolism. Four patients (2 were investigated before therapy, 2 when therapy had been already started) had acute Lyme neuroborreliosis, and 10 patients were investigated months to years after an acute infection. Increased concentrations of neopterin and of the tryptophan-degradation product, L-kynurenine, were detected in the cerebrospinal fluid of patients with acute Lyme neuroborreliosis; one patient presented with subnormal tryptophan. Similar but less marked changes were seen in the treated patients and in some of the patients with Lyme encephalopathy. No such abnormalities were seen in the serum of the patients. The data indicate a role of the immune system and particularly of endogenously formed cytokines, like interferon-gamma and tumour necrosis factor-alpha, effecting tryptophan and neopterin metabolism in patients with acute Lyme neuroborreliosis. PMID- 7865625 TI - Specific interference with the determination of the tumour-associated glycoprotein 72 by human anti-idiotypic antibodies formed after treatment with the anti-tumour-associated glycoprotein 72 antibody B72.3. AB - Recorded concentrations of the tumour-associated glycoprotein 72 (TAG-72) in ovarian cancer patients after repeated infusion of the antibody B72.3 were found to be falsely elevated when measured with an homologous immunometric assay involving the anti-TAG-72 antibody B72.3 (Test 1), or with an heterologous assay involving CC49 capture and B72.3 detector antibodies (Test 2). Test 1 yielded falsely elevated values up to 10(4) kU/l. Test 2 gave slightly false positive elevations up to 10(2) kU/l for only some of the samples with very high false positive values in Test 1. The interfering serum components bound to Protein G Sepharose and could be precipitated with perchloric acid or by heating serum samples to 100 degrees C. Addition of non-specific murine immunoglobulins only partly suppressed false-positive values in both tests. Our results suggest that this interference is caused by human anti-B72.3 IgG induced by B72.3 application, which to some extent specifically binds to determinants of the B72.3 antibody. Heat extraction of serum samples effectively eliminated interferences probably caused by anti-idiotypic antibodies, but did not affect real TAG-72. PMID- 7865626 TI - Expression of the erb B oncogene in the Morris hepatoma 7777. AB - Altered expression of protooncogenes/oncogenes is believed to be involved in hepatocarcinogenesis of the chemically induced, transplantable Morris hepatoma 7777. We compared the mRNA expression of c-N-ras and v-erb B mRNA of normal rat liver with that of Morris hepatoma 7777 using Northern blot analysis and in situ hybridization. Northern blot analysis revealed a strong overexpression of the v erb B related mRNA, while the c-N-ras mRNA was only slightly increased. In situ hybridization using a c-N-ras mRNA probe also showed only a slightly increased number of silver grains in the hepatoma cells compared with normal rat liver. On the other hand, the v-erb B related mRNA was strongly overexpressed in the hepatoma cells, while the connective-tissue capsule, the blood vessels, blood cells and the necrotic foci did not show an elevated v-erb B related gene mRNA expression. Similar results were obtained in liver metastases. The detectable v erb B hybridization signal was lost by pretreatment with RNase A. We conclude that the c-N-ras gene is of minor importance in the chemically induced, transplantable Morris hepatoma 7777, while the increased expression of the v-erb B related mRNA is due to a selection of ligand-independent tyrosine kinase activity. PMID- 7865627 TI - Measurement of salivary insulin-like growth factor-I in acromegaly: comparison with serum insulin-like growth factor-I and growth hormone concentrations. AB - The aim of this study was to establish the concentration of insulin-like growth factor-I (IGF-I) in saliva of acromegalic patients, and to compare it with the basal levels of serum IGF-I and growth hormone. IGF-I was determined in extracted serum or neat saliva by a disequilibrium RIA using antibodies and iodinated ligand from Amersham and WHO 87/518 as standard. The detection limit of the assay was 0.5 microgram/l, and the intra- and interassay coefficients of variations were 7.9% and 15% respectively. Our study included 13 healthy adult individuals and 17 acromegalics. Compared with healthy adult subjects, acromegalics had significantly higher salivary IGF-I concentrations (mean +/- SEM 5.4 +/- 2.64 vs. 10.5 + -5.69 micrograms/l; p < 0.01), as well as serum IGF-I (176 +/- 42.9 vs. 520 +/- 98.8 micrograms/l; p < 0.0001) and somatotropin levels (1.2 +/- 1.02 vs. 15.4 +/- 9.89 micrograms/l; p < 0.0001). However, 47.1% patients (8 out of 17) with active acromegaly had salivary IGF-I concentrations within the normal range. Serum IGF-I and somatotropin concentrations were found to follow more closely the disease activity after adenomectomy, compared with the concentrations of salivary IGF-I. These results suggest that the IGF-I levels in serum and saliva are somatotropin-dependent. According to our results, measurement of IGF-I in saliva cannot be considered as an additional measure for evaluation of the disease activity in acromegaly, being less reliable than the determination of IGF-I and somatotropin in serum. PMID- 7865628 TI - A manual spectrophotometric method for the measurement of serum sodium and potassium by enzyme activation. AB - Manual procedures suitable for use on standard benchtop spectrophotometers have been developed for the enzymatic determination of Na+ and K+ in serum. Both assays require only minimal modification of reagents already available for BM/Hitachi analyzers and are performed in an endpoint mode, allowing up to 20 assays per run. The addition of a stop reagent is required--dipotassium EDTA for the Na+ assay and sodium dodecyl sulphate for the K+ assay. The most important criterion for achieving good assay performance is the precise pipetting of sample and reagent. Within-run imprecision is < 1% for Na+ and K+, and between-run imprecision < 1.5%, for both assays at all but the lowest concentrations of K+. Enzymatic electrolyte results compare well with flame photometry, however the assays are more prone to interference by very high concentrations of bilirubin or triacylglycerols than those performed on automated, dual-wavelength kinetic analyzers. It is possible to correct for most interferences by inclusion of appropriate sample and reagent blanks. PMID- 7865629 TI - Influence of anticoagulants on the determination of blood glutathione peroxidase activity. AB - The influence of lithium heparin and heparin iodoacetate on the determination of blood glutathione peroxidase activity was investigated. Samples with each anticoagulant were taken from 393 lambs. Glutathione peroxidase activity was much higher in the lithium heparin samples (109.00 +/- 3.71 U/g Hb) than in the heparin iodoacetate group (31.05 +/- 1.55 U/g Hb). This difference was statistically significant (p < 0.001), and it was due to inhibition of glutathione peroxidase by heparin iodoacetate. Heparin iodoacetate therefore cannot be used as an anticoagulant in the determination of glutathione peroxidase in blood. PMID- 7865630 TI - Quality control of "one touch" II blood glucose meters used by nurses in clinical departments. AB - Most analyses of blood glucose concentrations in our hospital are performed bedside by nurses with One Touch II blood glucose meters. The laboratory is responsible for the test results and therefore a quality control system which includes the performance by the nurses, is necessary. Human serum, spiked sterilised horse blood and (spiked) human blood were tested with 39 One Touch II blood glucose meters for usefulness in extra-laboratory quality control schemes. Serum gave high imprecision (CV > 9%) and leaked through the strips, contaminating the meters. Horse blood gave unacceptable imprecision (CV = 6.7%) and human blood could not be used due to an unpredictable time course of the glucose values in the distributed samples. Addition of NaF increased the CV of the measurements by more than 2%. Only the One Touch control solutions (3 levels) resulted in satisfactory precision (CV = ca. 4%) and are therefore suitable for extra-laboratory quality control of precision. However, accuracy control has to be done within the laboratory with fresh human blood. PMID- 7865631 TI - The recovery of human saliva using the Salivette system. AB - Human saliva recovery using the Salivette system was investigated. Two Salivette systems were employed. The recommended centrifugation procedures for saliva recovery only recovered between 46% and 52% of the total volume. Modification of centrifugation speeds and duration allowed an 80% recovery. Differences were observed between the two Salivette systems tested with the newer system allowing a greater recovery. The findings have implications for saliva collection using this technique. PMID- 7865632 TI - Comparative study of four tests of bacterial infection in the neonate. Total neutrophil count, CRP, fibrinogen and C3d. AB - In a prospective study, the diagnostic value of C3d serum levels was compared with that of neutropenia, hyperfibrinogenemia and raised CRP in generalized neonatal bacterial infections. Serum C3d was evaluated using a counter immunoelectrophoresis technique following a step of removal of C3 split products. Twelve patients with septicemia, 8 patients with highly probable infection and 134 normal controls were included in the study. The sensitivities for neutropenia, hyperfibrinogenemia, raised CRP and positive C3d were 21, 45, 60 and 70%, respectively, with a significant difference between the sensitivities of neutropenia and positive C3d (p < 0.01). The specificities were found to be 99.2, 99.2, 100 and 97.7% respectively. Thus the C3d qualitative test appears to be as reliable as CRP in the diagnosis of neonatal bacterial infections. PMID- 7865633 TI - Prognostic significance of spontaneous motility in very immature preterm infants under intensive care treatment. AB - Qualitative analysis of spontaneous motility was performed in 22 preterm infants (gestational age 25-31 weeks) on the intensive care unit. The infants were videorecorded once a week in the late afternoon during 1 h until 36 weeks of gestation. Quality of movement was analyzed by 8 observers using visual 'Gestalt perception' and compared with the neurological outcome 1 year after term. A normal quality of movement consistently predicted a normal neurological outcome with a probability of 90-100%. An abnormal quality of movement predicted an abnormal outcome with a probability of only 56% in the first, but with a probability of 82% in the third postnatal week. The average interobserver agreement was 78%. The analysis of spontaneous motility for the early diagnosis of neurological dysfunctions can reliably be applied on very immature preterms under intensive care conditions from the 3rd postnatal week on. PMID- 7865634 TI - Short apneas and their relationship to body movements and sighs in preterm infants. AB - To test the hypothesis that there is an association among short apneas (3-10 s), body movements, and sighs, we studied 11 preterm infants (body weight 1,500 +/- 200 g, mean +/- SE; gestational age 30 +/- 1 weeks, postnatal age 28 +/- 5 days) using a flow-through system. A total of 1,166 apneas, 1,024 movements, and 473 sighs were recorded. Of the 1,166 apneas, 460 (39%) were associated with movements, 91 (8%) with sighs, and 226 (19%) with both movements and sighs. The rate of apneas associated with movements and sighs was significantly greater than expected if only a random association had occurred. These differences remained in quiet, rapid eye movement, and indeterminate sleep. The frequency of each of the three events was similar in a given sleep state. Of the 460 movements associated with apnea, 26% preceded, 23% followed, and 51% occurred during apnea. Similarly, of the 315 sighs associated with apnea, 44% preceded and 56% followed apnea. Apneas preceded by movements were longer than those without movements (5.6 +/- 0.2 vs. 4.9 +/- 0.1 s; p = 0.01). Oxygen saturation before apnea with movement (94 +/- 0.1%) was lower than before apnea alone (96 +/- 0.6%; p = 0.02) and also lower than before movement alone (96 +/- 0.1%; p = 0.001). These findings suggest: (1) there is a strong association among short apneas, movements, and sighs in these infants; (2) sighs appear not to be an isolated event and are likely to be part of a more general motor discharge, and (3) these events are accompanied by mild desaturations and bradycardias.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865635 TI - Hypoxia-ischemia in the neonatal rat brain: histopathology after post-treatment with NMDA and non-NMDA receptor antagonists. AB - In a model of perinatal hypoxic-ischemic brain damage, we examined the neuroprotective efficacy of posttreatment with the NMDA receptor antagonist MK 801 and the AMPA receptor antagonist NBQX. Unilateral brain damage developed in 95% of rat pups subjected to hypoxia-ischemia with a 27.8 +/- 1.2% weight deficit of the damaged hemisphere. MK-801 in doses of 0.3 and 0.5 mg/kg i.p. reduced the brain damage by 61% (p < 0.001) and 43% (p < 0.001), respectively. A higher dose of MK-801 (0.75 mg/kg) did not offer neuroprotection. Treatment with NBQX (40 mg/kg) reduced the hemispheric lesion by 28% (p < 0.05). In conclusion, posttreatment with both NBQX and low doses of MK-801 reduced perinatal brain damage. The NMDA receptor antagonist offered stronger neuroprotection which is in agreement with a proposed NMDA receptor hyperactivity around postnatal day 7 in rats. PMID- 7865636 TI - Regulation by glucose availability of tension development and electrical activity in fetal and neonatal rat hearts. AB - The aim of the present article was to study if changes in glucose availability modify the functional activity of the glucose-dependent developing heart. Our data indicate that a decrease in glucose availability increases tension development and action potential duration at early fetal stages. This fact could probably be explained by the enhancement of Ca2+ movements that regulate the number and turnover rate of membrane glucose transporters in muscle cells. The sensitivity to glucose availability decreases postnatally as the heart becomes fatty acid-dependent. PMID- 7865637 TI - Ornithine decarboxylase activity and concentrations of polyamines in embryos of diabetic rats. AB - Previous studies have demonstrated high concentrations of polyamines in neoplastic tissue and embryos and these compounds are therefore believed to play a role in cellular growth and embryonic development. Maternal diabetes causes embryonic dysmorphogenesis and alterations in embryonic polyamine concentrations may contribute to this process. In the present study we have measured the contents of DNA, putrescine, spermidine and spermine in embryos on days 10 and 11 of gestation in normal and diabetic rats. We also estimated the activity of ornithine decarboxylase (ODC) in embryos on days 9-11. We found that maternal diabetes causes delayed growth as reflected by decreased content of DNA on day 11 in the embryos of the diabetic group. Both the polyamine content and ODC activity were altered in the embryos of diabetic rats. Thus, the polyamines were increased on day 10 and decreased on day 11, and the ODC activity was decreased in a down regulated manner in day-10 embryos of the diabetic rats. These findings suggest that polyamine metabolism is involved in the dysmorphogenesis of diabetic pregnancy. PMID- 7865638 TI - Effect of intraventricular hemorrhage on pulmonary function in newborn piglets. AB - Intracranial hemorrhage in the premature infant is often associated with respiratory failure and need for mechanical ventilation. We therefore addressed the question of possible interactions with and pulmonary consequences of intraventricular hemorrhage. Newborn piglets were studied during intraventricular hemorrhage simulated by intraventricular blood infusion. Infusion volume amounted to 8% of estimated brain weight. Respiratory rate, minute ventilation, lung resistance and dynamic lung compliance, as well as arterial blood gases, arterial and intraventricular pressures were measured. The piglets were mechanically ventilated with a low basal rate of 20 breaths per minute throughout the study. All piglets experienced significant rise in intraventricular pressure and respiratory failure during the study. Respiratory failure was mainly a result of a reduction in respiratory frequency and minute ventilation until apnea. However, a rise in lung resistance was also noted while lung compliance did not change. We conclude that increased need for mechanical ventilation during intracranial hemorrhage is primarilty a consequence of hypoventilation. The increase seen in lung resistance could also suggest that intraventricular hemorrhage causes an element of bronchiolar constriction. Furthermore, these effects are not only a result of the increase in intraventricular pressure, but specific effects of blood components within the central nervous system must be considered. PMID- 7865639 TI - Review article: gastroduodenal bicarbonate secretion. AB - The gastroduodenal epithelium is covered by an adherent mucus layer into which bicarbonate is secreted by surface epithelial cells. This mucus-bicarbonate barrier is an important first line of defence against damage by gastric acid and pepsin, and has been demonstrated in all species including human. Similar to gastric acid secretion, regulation of gastric and duodenal bicarbonate secretion can be divided into three phases: cephalic, gastric and duodenal. In humans, sham feeding increases bicarbonate secretion in both the stomach and duodenum which is mediated by cholinergic vagal fibres in the stomach, but seems to be noncholinergic in the duodenum. Gastric distention and luminal acidification increases gastric bicarbonate production. Whereas there are no data relating to the gastric phase of human duodenal bicarbonate secretion, in animals, food and acid in the stomach independently stimulate duodenal bicarbonate output. To date, the duodenal phase of human gastric bicarbonate secretion has not been studied, but data from animals reveal that duodenal acidification augments bicarbonate secretion in the stomach. In all species tested, direct acidification of the duodenum is a potent stimulant of local bicarbonate production. In humans, the pH threshold for bicarbonate secretion is pH 3.0. Mediation of gastroduodenal bicarbonate secretion is provided by a variety of agonists and antagonists, tested mainly in animals, but some have been evaluated in humans. Prostaglandins of the E class and VIP are major factors that control bicarbonate secretion. Bicarbonate secretion, and the mucus-bicarbonate layer in general, is adversely effected by ulcerogenic factors such as aspirin, NSAIDs, bile salts, and cigarette smoking. Furthermore, duodenal ulcer patients have an impairment in bicarbonate production within the duodenal bulb, at rest and in response to stimulation. These findings indicate that the mucus-bicarbonate barrier is an important first line of defence in the pathogenesis of peptic ulcer disease. PMID- 7865640 TI - Scintigraphic assessment of the intragastric distribution and gastric emptying of an encapsulated drug: the effect of feeding and of a proton pump inhibitor. AB - BACKGROUND: Local delivery of therapeutic agents to the stomach may be a useful strategy in the treatment of Helicobacter pylori infection. We aimed to see whether the intragastric distribution and gastric retention of a therapeutic agent could be improved, either by giving omeprazole or by dosing after a meal. METHODS: Twelve healthy volunteers took part in this double-blind placebo controlled crossover study comparing the effects of omeprazole 20 mg twice daily for 5 days with placebo, and the fasted with the fed state, on the gastric emptying and intragastric distribution of a soluble scintigrapic marker contained in a drug capsule. RESULTS: Dosing after food profoundly prolonged gastric residence of the drug label, prolonging mean time to 50% emptying (T50) from 0.5 +/- 0.1 h in the fasted state to 2.0 +/- 0.2 h when given after food. Food also improved intragastric distribution by increasing delivery to the body and fundus. Omeprazole enhanced the effect of food, prolonging T50 to 2.9 +/- 0.3 h, but had no effect in fasted subjects. CONCLUSIONS: Dosing after food markedly improves the aspects of local drug delivery to the stomach investigated in this study, and omeprazole enhances this effect. Post-prandial dosing may, therefore, be useful for improving delivery of some anti-Helicobacter agents. PMID- 7865641 TI - Amoxycillin capsules with omeprazole for the eradication of Helicobacter pylori. Assessment of the importance of antibiotic dose timing in relation to meals. AB - BACKGROUND: Giving antibiotics after meals prolongs their gastric residence time and improves their intragastric distribution. We aimed to see whether this would result in improved eradication of Helicobacter pylori. METHODS: Eighty patients with H. pylori infection were treated with 40 mg omeprazole in the morning for 28 days and amoxycillin 500 mg q.d.s. for days 15-28. Amoxycillin dosing was randomised to either 1 h before or 10 min after food. Good compliance was pre defined as missing less than four doses of amoxycillin or two of omeprazole. RESULTS: Amoxycillin dosing after meals was shown not to affect H. pylori eradication rate either when results were analysed on an intention-to-treat basis [amoxycillin before meals successful in 63% (25/40), after in 65% 26/40)] or for good compliers only [before meals 81% (17/21), after 71% (20/28)]. This excludes, with 95% confidence, a benefit of greater than 18% from dosing before, or 23% from dosing after meals. Good compliance, however, was shown to be important, with H. pylori eradication in 76% (37/49) of good compliers compared with 48% (11/23) of others completing the protocol (P < 0.05). CONCLUSIONS: The timing of antibiotic administration in relation to meals is not important in the treatment of H. pylori infection with this regimen of amoxycillin capsules and omeprazole. Good compliance, is however, an important determinant of treatment success. PMID- 7865642 TI - Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. AB - AIM: To assess the efficacy of smooth muscle relaxants in the treatment of patients with irritable bowel syndrome, a meta-analysis of 26 selected double blind randomized trials vs. placebo was performed. METHODS: Five end-points were assessed: global assessment, abdominal pain, constipation, abdominal distension and the absence of adverse reactions. Analyses were performed according to the intention-to-treat method. For each end-point, the drug efficacy was assessed by the Der Simonian and Peto methods. When a significant difference was observed, sensitivity analyses were performed by successive stratifications according to the type of drug, the treatment duration, the prevalence of constipated patients, the trial design and the methodological quality. RESULTS: All myorelaxants analysed were significantly better than placebo for the improvement of global assessment (62% improvement rate vs. 35% on placebo, that is 27% improvement rate, P < 0.01) and for pain improvement (64% improvement rate vs. 45% on placebo, that is 19% improvement rate, P < 0.01). No significant differences were observed for constipation and abdominal distension. The percentage of patients with adverse reactions was significantly higher in patients receiving myorelaxants than placebo (6% mean difference, P < 0.01). CONCLUSION: According to this overview five drugs have proved their clinical efficacy in patients with irritable bowel syndrome, without significant adverse reactions: cimetropium bromide, pinaverium bromide, trimebutine, octilium bromide and mebeverine. PMID- 7865643 TI - Bran supplementation in the treatment of irritable bowel syndrome. AB - BACKGROUND: Irritable bowel syndrome remains the commonest reason for referral to a gastroenterology clinic. Patients with irritable bowel syndrome are frequently advised to increase their intake of bran fibre, despite inconclusive experimental evidence of benefit. METHODS: The effect of dietary supplementation with a bolus of bran fibre (12 g/day) was studied in a block-randomized, placebo-controlled, crossover study of 80 patients with irritable bowel syndrome referred to a District General Hospital outpatient clinic. Comparison of the benefits of bran and placebo was based upon personal assessment of individual and overall symptom profiles, determined from a simple daily symptom score and post-treatment interview. RESULTS: Overall symptomatic improvement was reported with bran by 52% and with placebo by 54% of patients. Bran supplementation was no more effective than placebo in improving individual symptoms of irritable bowel syndrome, and for wind-related symptoms it was significantly less effective (P < 0.001). CONCLUSION: Dietary supplementation with bran is of no value in the treatment of patients with irritable bowel syndrome referred to a hospital clinic. PMID- 7865644 TI - Low dose aspirin: selective inhibition of rectal dialysis thromboxane B2 in healthy volunteers. AB - AIM: To investigate the degree and selectivity of rectal thromboxane inhibition by low dose aspirin and there by investigate the contribution of platelet thromboxane to rectal thromboxane. METHODS: The study was a randomized double blind placebo controlled crossover study. Twelve healthy volunteers were studied, each over four separate study periods with two weeks wash-out between each period. Changes in levels of thromboxane (TX) B2, prostaglandin (PG) E2 and leukotriene (LT) B4 in rectal dialysates were measured in response to 5 days oral low dose aspirin therapy in one of three once-daily formulations (plain 75 mg, plain 300 mg or enteric coated 300 mg), and compared to placebo. For each study period, rectal dialysates (4 h duration) were obtained at baseline and twice more after 5 days of aspirin or placebo therapy. Dialysate levels of thromboxane B2, leukotriene B4, prostaglandin E2, and serum thromboxane B2 were measured by radioimmunoassay. RESULTS: Dialysate thromboxane B2 levels were consistently inhibited by low dose aspirin (overall results of all formulations, 75 to 300 mg daily) from 1.06 ng/ml (geometric mean, 95% CI: 0.79-1.43 ng/ml) on placebo, by 29% (95% CI: 11-40%) to 0.75 ng/ml (0.56-1.01 ng/ml) (P = 0.046) on aspirin. In the absence of aspirin the level of prostaglandin E2 was 1.47 ng/ml (0.97-2.23 ng/ml) and in the presence of aspirin was not significantly changed. The dialysate level of leukotriene B4 was 0.45 ng/ml (0.34-0.61 ng/ml) in the absence of aspirin and there was no significant change on low dose aspirin. Serum thromboxane was inhibited by 80% to 20% of placebo values by plain aspirin 75 mg, by 95% by plain aspirin 300 mg, and by 82% by enteric coated aspirin 300 mg, respectively (P < 0.01). These results show that 29% of the rectal thromboxane, but none of the rectal prostaglandin E2 or leukotriene B4 is inhibited by low dose aspirin. We infer that 34% of the rectal thromboxane B2 is platelet-derived in our volunteers. CONCLUSION: Low dose aspirin will selectively inhibit a proportion of rectal thromboxane and may have prophylactic therapeutic potential in inflammatory bowel disease. PMID- 7865645 TI - A selective NK-2 antagonist blocks the increase of canine colonic tone and ileal contractions induced by the NK-2 selective receptor agonist, [beta Ala8] neurokinin A-(4-10). AB - BACKGROUND: The regulatory roles of tachykinins in intestinal motor function may be clarified by use of novel, stable and selective antagonists of neurokinin receptors. We studied the effects of the non-peptide NK-2 receptor antagonist SR48968 on canine colonic tone under resting conditions and after stimulation by the selective NK-2 receptor agonist [beta Ala8] neurokinin A-(4-10). METHODS: Experiments were performed in three conscious female dogs. Proximal colonic tone was recorded by a barostat and intraluminal pressures were recorded in the terminal ileum. 10, 15 and 20 cm orad to the ileocaecal junction. In separate experiments, and in a random sequence, dogs received an i.v. injection of the NK 2 antagonist SR48968, 10, 100, 1000 micrograms/kg, followed after 30 min by 2 micrograms/kg of the agonist [beta Ala8] neurokinin A-(4-10). Experiments were replicated twice in each dog. RESULTS: The NK-2 agonist increased colonic tone, and SR48968 antagonized these effects in a dose-dependent fashion (Spearman's rank, r = 0.86; P < 0.01); antagonism was complete at the highest dose. SR48968 alone had no effect on colonic tone and ileal motility. When given during phase I or II of the interdigestive motor complex, [beta Ala8] neurokinin A-(4-10) increased ileal contractions: pre-treatment with SR48968 blocked this increase in ileal motility. When given during phase III, [beta Ala8] neurokinin A-(4-10) interrupted the motility front; this effect was not antagonized by SR48968. CONCLUSIONS: SR48968 antagonizes the increase in canine colonic tone and ileal motility induced by activation of NK-2 receptors. However, SR48968 by itself had no effect on the control of colonic tone and ileal motility under unstimulated conditions. SR48968 may be useful for investigating the physiological role of tachykinins on the gastrointestinal tract. PMID- 7865646 TI - Bioavailability of single and multiple doses of a new oral formulation of 5-ASA in patients with inflammatory bowel disease and healthy volunteers. AB - AIMS: An oral multiparticulate coated formulation of 5-aminosalicylic acid (5 ASA: mesalazine) has been developed to provide a controlled release of the drug, in a pH-dependent fashion, in the distal ileum and colon. The purpose of the present study was to assess the systemic availability of the drug and its metabolite, acetyl-5-ASA, following single (800 mg) and multiple (2400 mg for 56 days) oral dose administration. METHODS: Three groups were investigated: six healthy volunteers, six patients with ulcerative colitis, and nine patients with Crohn's disease in remission. In the single oral dose study (800 mg) all three groups participated, whereas in the multiple oral dose study (2400 mg/day for 56 days) only the patients with inflammatory bowel disease took part. Plasma and urine 5-ASA and Ac-5-ASA were measured for 48 h. RESULTS: In the single oral dose regimen, systemic absorption of 5-ASA and Ac-5-ASA were low and did not differ between the three groups. Only about 20% of the 5-ASA given was absorbed, with more than 80% of the drug being available in the terminal ileum and colon for therapeutic activity. The multiple oral dose regimen in patients with inflammatory bowel disease produced a significantly higher plasma concentration and urine excretion of both 5-ASA and Ac-5-ASA by the end of the treatment, in comparison to the first dose. There was a statistically higher systemic absorption of 5-ASA in patients with ulcerative colitis than in patients with Crohn's disease. After 56 days of dosing, no adverse event was reported and laboratory screening tests remained within normal ranges. CONCLUSIONS: The new oral 5-ASA formulation is gradually released throughout the small and large intestine, reflected by a low plasma concentration of the drug and its metabolite, with about 80% of the drug being available for ileum-colon therapeutic activity. PMID- 7865647 TI - Long term treatment with omeprazole 20 mg three days a week or 10 mg daily in the prevention of duodenal ulcer relapse. AB - BACKGROUND: The aim of this study was to compare omeprazole 10 mg o.m. (daily) with omeprazole 20 mg o.m. on Friday to Sunday inclusive (weekend) in the prevention of duodenal ulcer relapse over a 6-month period. METHODS: After an open healing phase (4 to 8 weeks) with omeprazole 20 mg o.m., 81 patients entered the follow-up phase. Forty-two were randomized in a double-blind double-dummy technique, to omeprazole 10 mg o.m., and 39 to omeprazole 20 mg at weekends. At 3 and 6 months or on symptomatic relapse the patients underwent endoscopy with gastric biopsies (quantitative assessment of argyrophilic and gastrin cells), symptom evaluation, and laboratory screening with fasting serum gastrin. RESULTS: Five patients in the 10 mg group and four in the weekend group were lost to follow-up. The estimated relapse rates over six months in the two groups receiving 10 mg daily or 20 mg at weekends were 19% and 31%, respectively (95% CI of percentage difference: -33% to 8%: intention-to-treat analysis, P = N.S.). During the follow-up phase, symptoms tended to be milder in the omeprazole 10 mg daily group compared to the weekend group. Gastrin levels increased significantly during the healing phase but then stayed almost constant in the omeprazole 10 mg group, and significantly decreased with weekend treatment. The median number of argyrophilic cells showed a slight but statistically significant increase in the omeprazole 10 mg daily group, but did not change in the weekend group. Both the healing and long-term therapies were well tolerated. CONCLUSIONS: Our data do not show a clear difference between the two treatment regimens, but there was a tendency towards a lower recurrence rate with omeprazole 10 mg daily compared with 20 mg weekend therapy. PMID- 7865648 TI - Effects of pantoprazole on endocrine function in healthy male volunteers. AB - METHOD: In a randomized, double-blind, two-period crossover study, pantoprazole 40 mg or placebo were given orally to 12 male volunteers for 2 weeks each. There was a wash-out period of at least 1 week between the two treatment periods. The effects of pantoprazole or placebo on cortisol and testosterone (primary criteria), and tri-iodothyronine, thyroxine, thyroid-stimulating hormone, thyronine-binding protein, parathyroid hormone, insulin, glucagon, renin, aldosterone, follicle-stimulating hormone, luteotrophic hormone, prolactin and somatotrophic hormone were compared. In addition, intragastric 24-h pH, 24-h H(+) activity, and volume of nocturnal gastric juice were determined by gastric aspiration technique. RESULTS: Pantoprazole did not influence plasma levels of testosterone, circadian cortisol concentrations or plasma cortisol levels after exogenous adrenocorticotropic hormone stimulation, as compared to placebo (P > 0.05, Koch's test). Furthermore, there were no clinically relevant changes with any of the other endocrine parameters. Pantoprazole significantly increased the median 24-h pH (group median 4.3 vs. 1.8; P < 0.001) and decreased 24-h H(+) activity (4.0 vs. 22.6 mmol/L; P < 0.001). The volume of nocturnal gastric juice did not significantly differ between the two treatments. Pantoprazole was well tolerated and the frequency of adverse events was similar to placebo. No drug related changes in laboratory values were observed. CONCLUSION: Pantoprazole did not influence endocrine function in healthy male volunteers during short-term treatment. PMID- 7865649 TI - Studies of water movement across the gut using oral rehydration solutions in a rat perfusion model. AB - AIM: To measure water influx and efflux, as well as net water, sodium and potassium absorption from a range of oral rehydration solutions (ORS) in which the glucose content had been partially replaced with the amino acid leucine or with food supplements. METHODS: A series of in vivo steady-state perfusion studies in normal rat intestine. The oral rehydration solutions contained 60 or 90 mmol/L of sodium. The reference solution used was the World Health Organization (WHO) formula. RESULTS: There was a significant negative correlation between the oral rehydration solution osmolality and net water absorption (r = 0.722, P < 0.05). The highest net water absorption occurred using comminuted chicken supplemented oral rehydration solution containing 60 mmol/L sodium (P < 0.001). This oral rehydration solution also showed a significant increase in the rate of influx of water (P < 0.05) in comparison with the WHO formula containing 60 mmol/L sodium. CONCLUSION: This work provides further evidence that food-based oral rehydration solutions, including non-vegetable sources, may have a useful role to play in the management of patients with acute diarrhoea. PMID- 7865650 TI - Comparative assessment of phenolphthalein and phenolphthalein glucuronide: is phenolphthalein glucuronide a better laxative? AB - BACKGROUND: Phenolphthalein is widely used as a safe and effective laxative. After oral administration, phenolphthalein is absorbed in the small bowel and is conjugated in the liver to phenolphthalein glucuronide which passes into the colon where it is deconjugated and the active compound, phenolphthalein, is released. Since phenolphthalein glucuronide does not undergo enterohepatic circulation it should theoretically have a more rapid onset of action and a lower threshold dose for laxation. The present study was designed to examine this issue. METHODS: Ten normal healthy subjects volunteered for the study. All subjects were administered placebo, phenolphthalein (at doses of 15, 30, 45, 60, 75 and 90 mg) or phenolphthalein glucuronide (at equivalent doses of 24, 48, 72, 96, 120 and 144 mg) in a random order. Stool weight, the frequency and consistency of stools, and the development of symptoms were recorded at 12-h intervals for 84 h. RESULTS: There was a significant increase in the mean stool weight obtained within the first 24 h of administration of a 30 mg dose of phenolphthalein and its glucuronide equivalent compared to the values obtained with placebo. A further increase in the dose did not improve the therapeutic response. There was no difference between phenolphthalein and phenolphthalein glucuronide with respect to the rapidity of action, the threshold dose, effectiveness of laxation, or the frequency of adverse effects. CONCLUSIONS: The therapeutic response and side effect profile of the different doses favoured 30 mg phenolphthalein as the optimum laxative dose. Although theoretically superior, phenolphthalein glucuronide was not found to be a more effective laxative compared to phenolphthalein in normal subjects. PMID- 7865651 TI - [Integration of medical behavior in community infections: its importance and significance]. PMID- 7865652 TI - [Effects of pharmacological doses of polyunsaturated fatty acids of the series 3 on the concentration of plasma lipoproteins]. AB - Cardiovascular disease is one of the main causes of death in developed countries. Its incidence may be modified through dietary changes, this being supported by the low incidence of the disease among populations with high intake of fatty fishes. The aim of this work was to study the modifications on plasmatic levels of polyunsaturated fatty acids omega 3 after an additional supply of fish oils and to assess its effect on the metabolism of lipids and lipoproteins. The study was conducted on 8 healthy volunteers, their age ranging between 24 and 37 years. They received, during 30 days and in tablets of 500 mg, 7.5 gr/24 h of fish oil concentrate which supplied 2.5 gr/24 h of fatty acids omega 3. After 12 hours of fasting, blood samples were taken before and after the intake of this concentrate. Methyl esters from fatty acids omega 3 were assessed through gas chromatography; cholesterol, triglycerides, LDL, VLDL, HDLt, HDL2 and HDL3, through several enzymatic techniques; and lipoprotein(a) Lp(a), through ELISA. The statistical analysis was conducted using the Student's method for matched data. After 30 days of supplement, we observed: a significant increase in the plasmatic percentage of fatty acids omega 3 (EPA + DHA) along with a significant decrease of triglycerides, VLDL and HDL3 and a significant increase of HDL2, We did not observe any significant changes in cholesterol, LDL and HDLt. With respect to Lp(a), after one month of dietary supplement, its plasmatic levels did not change. Our results supports the clinical usefulness of the dietary supplementation with fatty acid omega 3 for the management of hypertriglyceridemias.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865653 TI - [Immunity and malnutrition in alcoholic liver diseases]. AB - Assessment of immunity was performed in 150 patients with alcoholic liver disease (15 steatosis, 30 hepatitis and 105 cirrhosis: 34 in grade A, 34 in grade B and 37 in grade C, according to Child-Pugh classification). This assessment was based on the total lymphocyte count and a delayed hypersensitivity skin multiple test. Likewise, nutritional status of patients was studied using anthropometric and biochemical parameters (triceps skinfold thickness, arm muscle circumference and serum albumin). The association between alcoholic liver disease, malnutrition and immunity was analyzed. The results show that lymphopenia and disorders in cell mediate immunity were more common in those patients with cirrhosis, increasing the number of anergic patients while the degree of hepatocellular insufficiency worsens (8.8% in grade A, 11.8% in grade B and 32.4% in grade C). Although there where significantly more alterations of delayed cutaneous hypersensitivity in cirrhotics with malnutrition (hypoergy: 55.2% and anergy: 37.9%) than in those well nourished (hypoergy: 23.7% and anergy: 10.5%, p < 0.01), lymphopenia didn't show differences between these groups. We think that immunity mus'nt be considered a parameter in nutritional assessment. PMID- 7865654 TI - [Indications, performance and complications of bronchofibroscopy in the aged]. AB - Bronchofibroscopy is a widely used exploration for the diagnosis of several pulmonary processes. However, its use in aged patients, these being considered a high risk group, is still a controversial issue. The aim of this study was to analyze the indications, diagnostic performance and complications of the bronchofibroscopy in the elderly and to determine if there are any differences with respect to the adult population. A retrospective case control study was conducted, taking as cases those patients with 70 or more years of age, and as controls, those patients with less than 70 years. The study period was 1 year, with 54 bronchofibroscopies performed in 49 patients from the study group and 149 in 145 patients from the control group. The indications were similar in both groups, except for the study of opportunistic infections, these being more frequent among the control group. Diagnostic performance and complications did not show any differences between both groups. Indications, performance and complications of bronchofibroscopy in aged patients are similar to those in the adult population. Hence, the age in itself should not be a limiting factor for the indication of this exploration. PMID- 7865655 TI - [Hyponatremia upon admission in patients over 65 years of age. Relation with medium length of stay and hospital mortality]. AB - OBJECTIVE: To determine the relation between natremia levels equal to or lower than 130 mEq/l upon admission, and average length of stay and hospital mortality in patients with more than 65 years of age. DESIGN: Prospective case-control study lasting one year. LOCATION: Complejo Hospitalario San Millan-San Pedro (second-level hospital) in Logrono (La Rioja). PATIENTS AND METHODS: CASES: patients with more than 65 years of age and natremia levels equal to or lower than 130 mEq/l upon admission. CONTROL: normonatremic patients matched by age and sex. VARIABLES: average length of stay and hospital mortality. Comparative tests: Z-test comparing two mean values and Yate's chi-square continuity correction. RESULTS: With a 95% confidence, we have verified that the average length of stay of hyponatremic patients is between 1.44 and 9.2 days longer than in the case of normonatremic patients and the mortality rate is between 2.1 and 28.1% greater. CONCLUSION: Patients with hyponatremia upon admission have a longer average length of stay and a greater mortality. Plasmatic sodium levels equal to or lower than 130 mEq/l upon admission are associated to a poor prognosis in the latter evolution of the patient. PMID- 7865656 TI - [Recurrent infections, severe neutropenia and neutrophil chemotaxis defect in paroxysmal nocturnal hemoglobinuria]. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease, whose origin seems to lie in a acquired defect in the membrane of the pluri-potential hematopoietic cell. Chronic or intermittent acute hemolytic syndrome is the most frequent clinical manifestation, although in the literature there are also some references to the leukocytic and immunologic disorders of this disease. In this paper, we present the case of a 63-year-old patient with NPH who developed severe neutropenia and sustained febrile syndrome. In the past four years, she had suffered frequent episodes of fever and leukopenia, which apparently disappeared spontaneously. In the physical exploration, we observed hepatosplenomegaly. The hemogram showed mild iron deficiency anemia (hemoglobin 10.8 g/dl), severe neutropenia (neutrophil 0.3 x 10(9)/l) and significant reticulocytosis (610 x 10(9)/l). Iron deposits were greatly reduced in the marrow. Simultaneously to a new febrile episode and isolation of Escherichia coli in the urine, there was a severe anemization (hemoglobin 5 g/dl) and a significant thrombopenia (platelets 30 x 10(9)) resulting in a positive hemosiderinuria and sucrose test. The study of the leukocytic function showed a defect in the neutrophil chemotaxis, although a normal phagocytic capacity and microbicidal activity. In the following nine months, the patient had several severe infections, with intense but transitory pancytopenia, which always improved when treating the infection with antibiotics. The patient died due to a septic shock twelve months after the diagnosis. Recurrent febrile episodes and severe neutropenia are very rare in the PNH (less than 4% of the cases). The cause of these disorders is still unknown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865657 TI - [Thrombotic thrombopenic purpura and HIV infection. Apropos of a case]. AB - In the past years, more than thirty cases of thrombotic thrombocytopenic purpura (TTP) had been described associated to infection by the human immunodeficiency virus. Some authors have suggested the presence of a causal relationship between both entities, although the common nexus is still unknown. It usually has a fulminant onset, affecting all the risk groups and in any stage of the disease. The clinical manifestations are similar to the classical forms, as well as the evolution and response to treatment. We present a new clinical case, typical in its presentation and its good response to treatment with plasmatic spares associated to PFC and steroid infusion. We believe that the presence of clinical signs suggesting TTP in a patient would necessarily discard the presence of HIV infection and, the other way round, the presence of clinical signs suggesting TTP in a patient with HIV infection would determine the onset of an early and aggressive treatment based on plasmatic spares, given that the prognosis is linked to an early onset of the treatment. PMID- 7865658 TI - [Calcification of auricular cartilages in a patient with adrenal insufficiency: presentation of a case and review of the literature]. AB - Suprarenal insufficiency is the systemic disease more frequent associated to auricular cartilage calcification. Physiopathologic mechanism of this phenomenon remain without elucidate, several hypothesis have been postulated. We introduce one patient male attached of Addison's disease with external ear bilateral calcification. We review 20 case related in literature, postulating that low levels of cortisone, established in acute or chronic form, can cause a maintained or transitory hypercalcemia, calcium deposit in predisposed physically-chemically tissue: deficient peripheral vascularization and susceptibility to external aggression like traumatisms or cold. PMID- 7865659 TI - [Cryofibrinogenemia: apropos of a case]. AB - We describe the case of a 70-years-old woman with ischemic-hemorrhagic lesions in the cutaneous surface of both feet and analytical data of disseminated intravascular coagulation, in which the studies conducted were negative except for the presence of cryofibrinogen in plasma. We also review the clinical manifestations and the diseases associated to cryofibrinogenemia previously described in the literature. PMID- 7865660 TI - [Severe self-limiting hypersensitivity reaction after immunotherapy with intravesical BCG]. AB - We present the case of a 67-years-old patient diagnosed of superficial vesical transitional carcinoma which, under immunotherapy with intravesical BCG, developed a severe hypersensitivity reaction with spontaneous resolution. We describe several adverse reactions after the administration of intravesical BCG, as well as its diagnostic and therapeutic problems, especially in the cases of hypersensitivity. PMID- 7865661 TI - [Current aspects of hospital infections in medicine]. PMID- 7865662 TI - [Visceral leishmaniasis associated with disseminated intravascular coagulation. Apropos of a case]. PMID- 7865663 TI - [Upper digestive hemorrhage after oral administration of ketorolac]. PMID- 7865664 TI - [Blood transfusion using perfusion pump. A rare cause of hemolytic anemia]. PMID- 7865665 TI - [Pericarditis and Q fever]. PMID- 7865666 TI - [Severe hypokalemia in an attempted suicide by theophyllines]. PMID- 7865667 TI - [Hemoptysis caused by aspergilloma treated with radiotherapy]. PMID- 7865668 TI - [A new case of collagenous colitis]. PMID- 7865669 TI - [Non-secretory myeloma]. PMID- 7865670 TI - [Pulmonary complications and cocaine. Apropos of a new case of pneumomediastinum]. PMID- 7865671 TI - [Wallenberg and Opalski syndrome]. PMID- 7865672 TI - Heparin-coated oxygenators significantly reduce contact system activation in an in vitro cardiopulmonary bypass model. AB - Over the past decade our group has shown that the contact system of blood is activated in cardiopulmonary bypass (CPB), that heparins enhance this activation and that aprotinin reduces both this activation and blood loss in CPB. We have developed an in vitro CPB model to assess the effects of added components to blood and new components in the artificial devices of CPB. In the present study we have compared membrane oxygenators with or without heparin-coated surfaces under identical conditions in the CPB model. Recalcified ACD blood was circulated in a closed system for 90 min at 28 degrees C. Blood samples were taken at various times during circulation. 4 IU/ml heparin was used with the non-coated oxygenators; no heparin was used in the coated system. Heparin levels were measured in the plasma together with various contact system components. Haemolysis, platelet count, platelet factor 4 and alpha 1-proteinase inhibitor PMN elastase complexes, were also determined. No heparin was detected during the period of recirculation in samples from the coated oxygenators, showing the excellent adhesive quality of the heparin coating. In keeping with a significant greater fall in the platelet count in non-coated vs coated oxygenators (mean [+/- SD] final counts of 170 +/- 50 x 10(9)/l and 97 +/- 34.2 x 10(9)/l respectively after 90 min circulation), platelet factor 4 levels were significantly higher (682.9 +/- 187.3% and 95.8 +/- 46.5% of the initial value respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865674 TI - Six missense mutations associated with type I and type II protein C deficiency and implications obtained from molecular modelling. AB - The molecular basis of protein C deficiency was studied in three type I and three type II heterozygotes. Three probands showed thrombotic complications. All the exons and intron/exon junctions of the protein C gene were studied using a strategy combining by the polymerase chain reaction (PCR) amplification, single strand conformational polymorphism (SSCP) analysis, and DNA sequencing of the PCR amplified fragments. Six missense mutations were identified, including three novel ones. One was located in exon II, in which the initiating translation codon (ATG) encoding for Met at position -42 was replaced by ACG encoding for Thr. The other five were located in exon IX, and included TAC(Tyr399)-->CAC(His), CCG(Pro327)-->CTG(Leu), GAC(Asp359)-->AAC(Asn) in two cases, and GGG(Gly350)- >AGG(Arg). Four of the six missense mutations occurred in CG dinucleotide. Sequence analysis of the other exons excluded additional mutations. By restriction enzyme analysis, co-segregation of the mutation with protein C deficiency was observed in four families. The other two mutations at amino acid positions -42 and 350 were also considered to be associated with protein C deficiency due to the absence of these mutations in 50 normal individuals. A structural model of the protease domain of mutant activated protein C was constructed by the chimeric modelling method, and the resultant model suggested conformational changes due to each missense mutation identified in protein C deficiency. The present data also provide some evidence regarding the genetic heterogeneity of protein C deficiency. PMID- 7865673 TI - Relationship of fibrinolysis and platelet function to bleeding after cardiopulmonary bypass. AB - In order to study the effects of cardiopulmonary bypass (CPB) on fibrinolysis and platelet function and the possible relationship of these effects on post operative blood loss, 127 patients undergoing CPB were examined. There was a significant reduction in the median levels of fibrinogen, plasminogen, alpha 2 antiplasmin, fibrinolytic potential and platelet aggregation during CPB (P < or = 0.001). Median levels of soluble fibrin, fibrinogen degradation products, D-dimer and PAI-1 were increased, while the level of t-PA activity remained constant. Post-CPB levels of fibrinogen and plasminogen correlated negatively with blood loss (P = 0.003 and P < 0.001, respectively) and interestingly, lower levels of alpha 2-antiplasmin and higher levels of t-PA activity before CPB were associated with greater blood loss after CPB (P < 0.001 and P = 0.004, respectively). Better pre-CPB platelet function correlated with lower levels of D-dimer before and after CPB. As expected, haemodilution had a significant effect on fibrinolytic and coagulation parameters post-CPB; the greater the haemodilution, the more the concentration of fibrinogen, plasminogen and alpha 2-antiplasmin fell post-CPB and the greater the blood loss. The increase in PAI-1 levels intra-CPB appeared to result in mean t-PA activity remaining unchanged 1 h post-CPB. Post-CPB increases in soluble fibrin were paralleled by increases in fibrinogen degradation products and D-dimer, suggesting that intra-operative contact activation is related to activation of the fibrinolytic system. The present findings indicate the greater the fibrinolytic activation, the greater the post CPB blood loss. PMID- 7865675 TI - Course of thrombin activation markers in patients implanted with Palmaz-Schatz stents: first experiences with a post-interventional anticoagulation regimen. AB - Following implantation of coronary Palmaz-Schatz stents, 29 patients were anticoagulated with a combination of heparin, phenprocoumon and aspirin following a standard protocol. After removing the arterial and venous lines, post interventional intravenous (i.v.) heparin treatment started with 1500 IU/h for patients > 80 kg and 1250 IU/h for patients < 80 kg. Heparin was monitored by the activated partial thromboplastin time (aPTT) and adjusted by increasing or reducing i.v. heparin by 250 IU/h to maintain the aPTT within the therapeutic range. Phenprocoumon therapy began the day after stent implantation (day 2) and lasted for 3 months. aPTT, Heptest, prothrombin fragment F1 and 2 (F1.2) and thrombin-antithrombin III complexes (TAT) were monitored at standard intervals for 10 days (mean monitoring time: 9.7 +/- 2.3 days). Anticoagulation was efficient with aPTT levels remaining within the therapeutic range on day 9 and the simultaneous, moderate-onset oral anticoagulation within the therapeutic range of the International Normalized Ratio (INR; 2.15-4.80) on day 8 on average, the mean INR being 2.43 +/- 0.76. On day 4, F1.2 levels were significantly higher than on the day of stenting (1.16 +/- 0.30 nmol/l vs 1.04 +/- 0.53 nmol/l; P < 0.005). F1.2 levels fell after day 5, the difference becoming significant from day 8 on (P < 0.05). F1.2 was negatively correlated with the Heptest (P < 0.05) and fell significantly as a function of the INR during phenprocoumon administration (P < 0.001). After phenprocoumon therapy was discontinued over 3 weeks, 25 patients were followed up by angiography. Despite adequate anticoagulation, mean F1.2 levels in patients showing restenosis at follow-up angiography were significantly higher (P < 0.005) than in those without restenosis. In one patient who developed subacute stent thrombosis, clotting factors were determined 20 min before stent occlusion. The levels of F1.2 and TAT were less than all other patients on this day (F1.2: 0.98 nmol/l vs 1.11 +/- 0.40 nmol/l; TAT: 2.7 micrograms/l vs 3.21 +/- 3.38 micrograms/l). Thus, neither F1.2 nor TAT predicted the occurrence of thrombotic stent failure in individuals. Efficient anticoagulation by a combination of anticoagulants is imperative for stent implantation. Using only current routine methods, this way of monitoring anticoagulation is effective for managing combined anticoagulation therapy. PMID- 7865676 TI - Increased vascular endothelial cell markers in patients with chronic renal failure on maintenance haemodialysis. AB - Plasma levels of the vascular endothelial cell markers, thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (t PA), and von Willebrand factor (vWF) were measured in 55 patients on maintenance haemodialysis (HD). TM, PAI-1 and vWF antigen levels were significantly increased in patients before HD, but t-PA antigen was not Compared with levels before HD, t PA and vWF antigens were significantly increased 1 h after HD and at the end of HD. TM antigen was significantly increased 1 h after HD, and plasma PAI-1 antigen was decreased at the end of HD. TM and vWF antigen levels were negatively correlated with the time (years) on HD. It is concluded that HD may cause endothelial cell damage and that the increases in plasma TM, PAI-1 and vWF levels before HD, and the decrease in the release of TM and vWF antigens from vascular endothelial cells, might be caused by vascular endothelial cell damage from long term HD. PMID- 7865677 TI - Changes in clot deformability--a possible explanation for the epidemiological association between plasma fibrinogen concentration and myocardial infarction. AB - This study examined the rheological properties of fibrin gels formed by adding thrombin to plasma samples from 99 subjects with fibrinogen concentrations ranging from 1.45 to 4.14 g/l. A highly significant (r = 0.757; P < 0.001) inverse correlation was observed between plasma fibrinogen concentration and the extent of clot deformability as estimated from the final value of the storage modulus (G') of the fibrin gel when obtained by rheological analysis. A similarly significant correlation (r = 0.844; P < 0.001) was obtained using samples from 47 subjects in which fibrin cross-linking was blocked by addition of 0.1 mM iodoacetamide to inactivate factor XIIIa. The characteristics of the relationship between G' and fibrinogen concentration in the plasma samples was comparable with that observed when the fibrin gel was formed by adding thrombin to purified fibrinogen. These results suggest that the increased risk of myocardial infarction associated with an elevated plasma fibrinogen concentration may, in part, be explained on the basis of a decreased deformability of the fibrin clot formed. PMID- 7865678 TI - Plasma levels of soluble fibrin in patients with malignancy-associated disseminated intravascular coagulation. AB - Disseminated intravascular coagulation (DIC) is one of the most critical complications of malignant diseases. It is conventionally diagnosed by a decrease in platelets and an increase in fibrin/fibrinogen degradation products (FDP). Recently, an immunological assay was developed that can directly quantify the amount of soluble fibrin (SF) formed in the blood. This study examined this assay system in the diagnosis of DIC and found that it is a good indicator of both fibrin formation and of DIC. Plasma levels of SF correlated well with the DIC score, which is determined according to the 'DIC Scoring Guideline' proposed by the DIC Study Group under the Japanese Ministry of Public Welfare in 1988. It also correlated well with the serum levels of FDP. Normal values of plasma SF ranged between 0 and 9.50 micrograms/ml. Interestingly, values of SF in females tended to increase with age, for reasons that are not yet determined. PMID- 7865679 TI - The coagulopathy of heat stroke: alterations in coagulation and fibrinolysis in heat stroke patients during the pilgrimage (Haj) to Makkah. AB - Haemostatic measurements were undertaken in 132 patients diagnosed with heat stroke during the pilgrimage to Makkah, in two successive summers of 1989-90. The control group comprised 49 patients, all pilgrims, with a wide range of clinical conditions, but without hyperpyrexia or deranged haemostasis. Heat stroke patients showed (i) significant prolongation of the prothrombin (PT), activated partial thromboplastin (aPTT) and thrombin times (TT) but normal reptilase time (RT); (ii) significant reduction in plasma levels of antithrombin III (AT-III), factor V, proteins C and S, plasminogen activator inhibitor (PAI) and platelet count; (iii) increase in plasma factor VIII, tissue plasminogen activator (t-PA) and serum FDP; (iv) no significant changes in plasma fibrinogen, plasminogen, alpha 2-antiplasmin and factors VII and X. Heat stroke patients were then grouped into those with and those without bleeding symptoms. Bleeders showed greater prolongation of the PT, aPTT and TT and significant reductions in fibrinogen, AT III, factors V, VIII and X, plasminogen, alpha 2-antiplasmin and platelet count. Logistic regression and discriminant analysis showed that AT-III was the parameter associated most with heat stroke and reliable enough to predict its occurrence, whether or not bleeding occurred. The results indicate that activation of the haemostatic mechanism, consumptive in nature, regularly accompanies heat stroke and highlights the physiological role of AT-III in checking this activation process. PMID- 7865680 TI - Characterization of adhesion of non-exogenously stimulated and resting platelets in normal plasma to fibrinogen and its fragments. AB - Platelet adhesion to various forms of fibrinogen was studied using platelets in plasma and washed platelets. The study was designed to determine if platelets prepared with minimal handling in plasma at physiological pH containing normal levels of Ca2+ have different requirements for adhesion to immobilized fibrinogen than do washed platelets tested in the absence of plasma. Exposure of platelets to citrate and low pH did not seem to affect the requirements of washed platelets for adhesion to fibrinogen. Nonetheless, behavioural differences between these two types of platelets were seen. Surprisingly, in the absence of exogenous activation normal platelets in plasma behaved qualitatively as stimulated washed platelets. That is, both types of platelets adhered to all forms of fibrinogen which possessed at least one gamma-chain carboxyl terminal platelet binding site. Platelets in plasma treated with prostaglandin E1 (resting platelets) adhered only to forms of fibrinogen which contained two gamma-chain platelet binding sites. These observations also demonstrate that the fibrinogen alpha-chain arginine-glycine-aspartic acid-phenylalanine and arginine-glycine-aspartic acid serine sequences are not necessary or sufficient to mediate the adhesion of resting or stimulated platelets in plasma to fibrinogen. The presence of endogenous adenosine diphosphate appears to account, at least in part, for the ability of normal platelets in plasma to adhere to forms of fibrinogen which have only one gamma-chain platelet binding site. PMID- 7865682 TI - Results of a collaborative study for fibrinogen measurement. Evidence that the use of a common calibrator improves interlaboratory agreement. AB - One hundred and sixty-five laboratories were asked in two different surveys to perform duplicate fibrinogen measurements on the same lyophilized plasmas by their own methods and reagents and two different methods of calibration. The between-laboratory variability, expressed as coefficient of variation (CV), and the extent of between-method and between-reagent differences were taken as a measure of agreement between measurements. It was found that the overall between laboratory range of CV values was 9-16% and that it could be improved if a common calibrator was used. The improvement was more pronounced for the thrombin time derived (Clauss) method (average CV reduction 43%) than for the prothrombin time (PT)-derived method (average CV reduction 12%). A satisfactory agreement was found between the PT-derived and the Clauss method for the normal-PT plasma, whereas the PT-derived was slightly higher than the Clauss method for the abnormal-PT plasmas, irrespective of calibration. There were statistically significant between-reagent differences within the Clauss method, which were reduced if the common calibrator was used. In conclusion, the results shows that a system of common calibration for fibrinogen determination improves interlaboratory agreement by reducing the CV and minimizing between-reagent differences, particularly for the Clauss method. The authors recommend manufacturers of reagents to link their calibrators to the International Standard for fibrinogen. PMID- 7865681 TI - Tissue factor pathway inhibitor prevents thrombus formation on procoagulant subendothelial matrix. AB - The effect of recombinant tissue factor pathway inhibitor (rTFPI) on extracellular matrix procoagulant activity was studied in a human ex vivo model of thrombogenesis. Extracellular matrix of endotoxin stimulated endothelial cells perfused with human non-anticoagulated blood at a wall shear rate of 100/s induced pronounced fibrin deposition, which covered 82 +/- 11% of the matrix surface within 5 min. Preincubating the matrix with the combination of rTFPI, factor VIIa (FVIIa) and factor Xa (FXa) reduced fibrin deposition to levels observed with matrix from non-stimulated endothelial cells (7 +/- 6% fibrin coverage, P < 0.001). Preincubation with rTFPI plus FXa also reduced fibrin deposition significantly, but to a lesser extent (41 +/- 6% fibrin coverage, P < 0.001). Preincubation with rTFPI alone, or with rTFPI plus FVIIa, did not affect fibrin deposition. The inhibition of thrombus formation on procoagulant extracellular matrix by rTFPI seemed to be FXa-dependent, and a result of TFPI's ability to bind and inhibit both TF activity as well as FXa. The results from this study suggest a future role for rTFPI as an agent for prevention of TF induced vascular thrombosis. PMID- 7865683 TI - Fibrinogen present in EDTA--anticoagulated plasma stimulates the tissue-type plasminogen activator-catalysed conversion of plasminogen to plasmin. AB - The presence of soluble fibrin in plasma is an early and sensitive indicator of activation of the coagulation system. Quantitative spectrophotometric assays for soluble fibrin can be based on the principle that soluble fibrin stimulates the tissue-type plasminogen activator-catalysed conversion of plasminogen to plasmin. It was previously shown that treatment of purified fibrinogen by EDTA, which removes the three tightly bound Ca2+ ions, results in exposure of tissue-type plasminogen activator-catalytic sites similar to those unveiled by thrombin. Since EDTA is a common anticoagulant, it was of interest to study the effect of EDTA on a test based on plasminogen activation. It is concluded that the determination of soluble fibrin in EDTA-anticoagulated plasma from healthy individuals gives a false positive indication of the presence of soluble fibrin. This was true irrespective of whether the test was performed at pH 7.4, 7.8 or 8.5. The most probable explanation is that tissue-type plasminogen activator stimulating sites are exposed in fibrinogen by EDTA. Therefore, EDTA-plasma is unsuitable for assaying soluble fibrin with tests based on the tissue-type plasminogen activator-mediated conversion of plasminogen to plasmin. PMID- 7865684 TI - Anticoagulant and antiprotease activities of aprosulate sodium, a new synthetic polyanion, in human plasma and purified systems. AB - Aprosulate sodium, a new synthetic polyanion, was evaluated for anticoagulant/antiprotease activities in vitro. Aprosulate prolonged activated partial thromboplastin time (aPTT), Heptest and thrombin time (TT) with the sensitivity order of aPTT > Heptest > TT. Prothrombin time (PT) was hardly affected by the agent. Since these results indicated that inhibition of the intrinsic coagulation cascade was important for the anticoagulant activity of aprosulate, amidolytic assays were subsequently performed to characterize antiprotease activities of the agent in the common and intrinsic pathways. Aprosulate inhibited amidolytic activity of thrombin in the presence of heparin cofactor II, but was devoid of direct and antithrombin-mediated anti-factor Xa, and direct anti-factor XIIa activities. However, aprosulate was found to be a potent inhibitor of amidolytic activity of factor Xase (IXa/VIIIa). These data suggest that the direct anti-factor Xase activity of aprosulate primarily contributes to its anticoagulant activity in the intrinsic coagulation cascade. PMID- 7865685 TI - Basal plasma concentration of tissue plasminogen activator (t-PA) and the adaption to strenuous exercise in familial hypercholesterolaemia (FH). AB - Epidemiological studies have provided evidence that attenuated fibrinolytic activity and increased antigen levels of plasminogen activator are risk factors for coronary heart disease (CHD). In a comparative study, tissue plasminogen activator (t-PA) antigen and activity concentrations were examined in plasma from familial hypercholesterolaemia (FH) patients without manifest CHD (n = 14) and in age- and sex-matched normolipaemic controls (NLC) at rest and after the same bicycle exercise. The FH patients had higher systolic and diastolic blood pressure than their controls. The plasma level of t-PA antigen was higher in FH patients than in NLC under basal conditions (7.3 +/- 3.1 ng/ml vs 4.8 +/- 2.2 ng/ml, P = 0.022), whereas no difference was found in t-PA activity. Bicycle exercise induced a marked increase in t-PA antigen (P < 0.001 for both groups) which did not differ between groups. A more prominent rise in t-PA activity was observed among the FH patients during the exercise (1.71 +/- 0.99 vs 0.85 +/- 0.89 IU/ml, P = 0.24). Neither the basal level of thrombin-antithrombin III complex (TAT) nor the significant increase (P < 0.001 for both groups) induced by exercise differed between groups. A high t-PA antigen level may precede clinical manifestations of cardiovascular disease in patients with familial hypercholesterolaemia. PMID- 7865687 TI - Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin). An experimental investigation in healthy volunteers. AB - The aim of the present study was to investigate whether tinzaparin sodium (a low molecular-weight heparin (LMWH)) was fully and permanently neutralized in vivo in man by protamine sulphate (PS) after intravenous (i.v.) or subcutaneous (s.c.) injection. Fifty healthy adults equally divided in five age- and sex-matched groups were included. The groups received 50 IU unfractionated heparin (UH)/kg body weight (b.w.) i.v., 50 anti-factor Xa (anti-Xa) IU tinzaparin/kg b.w. i.v., 75 anti-Xa IU tinzaparin/kg b.w. s.c., 175 anti-Xa IU tinzaparin/kg b.w. s.c., or 1 ml of saline s.c. PS was given as a 10 min infusion in a dose of 1 mg/100 IU of heparin in the four first groups while 0.5 mg PS/kg b.w. was given in the placebo group. In the i.v. groups PS was administered 45 min after the heparin injection, and in the s.c. groups 180 min post-heparin injection. In the UH group PS fully and permanently neutralized all three activities. In the i.v. tinzaparin group PS reversed 80% of the anti-Xa activity, while the anti-IIa and aPTT activities were fully reversed. A slight, but statistically significant, increase in anti-Xa and anti-IIa activities were seen following i.v. tinzaparin. In the s.c. groups 60 65% of the observed peak anti-Xa activity was neutralized, anti-IIa was almost completely reversed, and aPTT returned nearly to baseline values. A gradual return of the anti-Xa activity (65-75%), anti-IIa activity (55%) and aPTT activity (35-45%) was seen in the s.c. groups 3 h after reversal compared with the observed peak values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865686 TI - Is the coagulopathy of hepatosplenic schistosomiasis immune-related? AB - Some of the soluble factors that affect haemostasis produced in the course of hepatosplenic schistosomiasis, including endotoxins (Ex), interleukin-1 alpha (IL 1 alpha) and tumour necrosis factor-alpha (TNF-alpha) were studied. Forty-one patients with hepatosplenic schistosomiasis were studied and classified into early hepatosplenic schistosomiasis (n = 12), hepatocellular decompensation (n = 14), vascular decompensation (n = 15) as well as twelve healthy controls. Thrombin-antithrombin complex (TAT), protein C and free protein S antigen and activity, endotoxin, IL-1 alpha and TNF-alpha levels were measured in all cases. Evidence of enhanced thrombin generation (elevated TAT levels) with reduced anticoagulant potential (reduced protein C and free protein S antigen and activity levels) could be demonstrated, thus reflecting decreased production and increased consumption of both coagulant and anticoagulant proteins. The association of high Ex, IL-1 alpha and TNF-alpha levels may suggest their possible implication in the causation of intravascular coagulation in hepatosplenic schistosomiasis. PMID- 7865688 TI - British Society for Haemostasis and Thrombosis. London, 12 September 1994. Abstracts. PMID- 7865689 TI - Measurement of tissue factor pathway inhibitor in normal and post-heparin plasma. AB - Assay methods for the detection of both tissue factor pathway inhibitor (TFPI) function (two-stage chromogenic assay) and for TFPI antigen levels (competitive ELISA) have been developed and applied to the measurement of TFPI in normal plasma, in post-heparin plasma and to recombinant TFPI. There was good correlation in TFPI levels, measured using the two methods (r = 0.848; P < 0.001) in the normal plasma samples (n = 21) with the values ranging from 0.6 to 1.4 units per ml relative to a normal reference plasma pool (assigned 1.0 unit per ml). The post-heparin plasma samples were associated with increased levels of both TFPI functional activity and antigen. However, there was poor correlation between the two methods, with an increase in antigen levels greatly exceeding the increase in functional activity. This discrepancy was also found with recombinant TFPI and may reflect the different responses of the two assay methods to lipoprotein-bound TFPI (in the normal plasma reference) and the 'free' TFPI in post-heparin plasma and recombinant TFPI. These findings have implications in the choice of suitable reference materials for the assay of TFPI. PMID- 7865690 TI - Homozygous factor V-deficient patients show resistance to activated protein C whereas heterozygotes do not. AB - Resistance to activated protein C (APC resistance) was assessed in plasma from patients with heterozygous and homozygous factor V (FV) deficiency. Because of the identity of the new APC cofactor with non-activated FV, it was expected that the lower the FV level the higher the APC resistance in plasma. Heterozygotes for the FV defect (both antigen and activity levels around 40%) did not show APC resistance in plasma. In contrast, homozygous patients for the same defect (less than 1% antigen and activity levels), had obvious APC resistance. Whether this finding was consistent with a spurious APC resistance or whether it truly reflected the lack of the APC cofactor activity in congenital FV deficiency remains to be clarified. Mixing (1:1) plasma from patients with a homozygous FV defect with pooled normal plasma (PNP) corrected both procoagulant and anticoagulant FV activities. Whenever severely APC-resistant plasma was used in place of PNP, only procoagulant activity was corrected and APC resistance was not affected. This suggests that homozygous FV-deficient plasma completely lacks the cofactor, i.e. the second APC cofactor, which can correct APC resistance in plasma. This indirectly confirms that the second APC cofactor is related to FV. PMID- 7865691 TI - Study of the balance between coagulation and fibrinolysis in disseminated intravascular coagulation using molecular markers. AB - Plasma levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC) and active plasminogen activator inhibitor (PAI) were assayed in 66 cases of disseminated intravascular coagulation (DIC). Significant elevation of both TAT and PIC was observed in all cases of DIC. Most elevated levels of TAT were seen in DIC with acute promyelocytic leukaemia (APL) and sepsis. The highest levels of PIC were seen in DIC with APL but were much lower in sepsis. A significant elevation in active PAI was observed in DIC due to acute leukaemia (apart from APL), chronic myeloid leukaemia and sepsis, but not in APL, non-Hodgkin lymphoma and cancer. Active PAI was higher in patients with multiple organ failure (MOF) than in those without MOF while PIC was lower in patients with this complication. Thus, the balance of coagulation and fibrinolysis varied according to the underlying cause of DIC; APL had more dominant activation of fibrinolysis, while sepsis had greater activation of coagulation. It is suggested that the inhibition of secondary fibrinolytic activation plays an important role in the progression of MOF by the disturbance of the microcirculation. PMID- 7865692 TI - Acquired factor VII deficiency associated with pleural liposarcoma. AB - Isolated acquired factor VII (FVII) deficiency (0.15 U/ml) was identified in a 30 year-old man with pleural liposarcoma. The patient underwent surgery with continuous FVII concentrate infusion. No anti-FVII antibody or FVII/anti-FVII complex was detected. However, the short half-life and low recovery of FVII after concentrate infusion suggested the presence of an antibody. Whatever the mechanism, this FVII deficiency was related to the presence of the liposarcoma. FVII level normalized during tumour regression and fell again when the liposarcoma relapsed. PMID- 7865693 TI - A data management program for the Electra 800 automatic analyser. AB - The Electra 800 automatic coagulation analyser rapidly performs most chronometric coagulation tests with high precision. To facilitate data handling, software, adaptable to any PC running under MS-DOS, was written to manage the analyser. Data are automatically collected via the RS232 interface or can be manually input. The software can handle 64 different analyses, all entirely 'user defined'. An 'electronic worksheet' presents the results in pages of ten patients. This enables the operator to assess the data and to perform verifications or complementary tests if necessary. All results outside a predetermined range can be flagged and results can be deleted, modified or added. A patient's previous files can be recalled as the data are archived at the end of the day. A 120 Mb disk can store approximately 130,000 patient files. A daily archive function can print the day's work in alphabetical order. A communication protocol allows connection to a mainframe computer. This program and the user's manual are available on request, free of charge, from the authors. PMID- 7865695 TI - Plasma thrombomodulin levels increase with the severity of the diabetic retinopathy. PMID- 7865694 TI - Prothrombin Padua I: incomplete activation due to an amino acid substitution at a factor Xa cleavage site. AB - An individual and an affected brother previously identified as having the variant prothrombin Padua I were studied in order to identify underlying genetic defects. A heterozygous mutation in the prothrombin gene exon 8 was identified as substitution of A for G at nucleotide position 7,312 (Arg271 (CGT) to His (CAT)). An abolished RsaI restriction site was used to confirm heterozygosity for the defect. Lack of the requisite cleavage of the His271-Thr272 bond in prothrombin Padua I could prevent release of fragment 2 and block the conversion of the intermediate meizothrombin des fragment 1 to alpha-thrombin, providing an explanation of reduced potential for clotting activity and for the observed mild bleeding tendency. PMID- 7865696 TI - High stability of dilute human alpha-thrombin in salt solutions. PMID- 7865697 TI - How to calculate the maximum risk. PMID- 7865698 TI - Resistance to activated protein C is reduced in women using oral contraceptives. PMID- 7865699 TI - Royal College of Physicians of Edinburgh 2nd International Symposium on Fibrinogen and Cardiovascular Disease. 1-2 November 1994. Abstracts. PMID- 7865700 TI - Meet our challenge: why a broadly encompassing paradigm in psychogeriatrics is essential. PMID- 7865701 TI - Weight loss in Alzheimer's disease: an international review of the literature. AB - Alzheimer's disease affects an estimated 2 million elderly in the U.S. and challenges primary care physicians to assist caregivers in dealing with the daily management of these patients. To support the clinical observation of weight loss in Alzheimer patients despite adequate food intake, we reviewed the existing literature. To date, eight international studies have focused on nutrition in Alzheimer's disease and all have found weight loss. It is not clear whether this weight loss is a component of or a consequence of the disease. These findings suggest systemic, metabolic alterations in Alzheimer's disease. They require further investigation as to their nature and as to their appropriate recognition and management to retard the deteriorating effects of chronic weight loss and malnutrition. Finally, some reports lead to speculation that nutritional strategies may improve cognitive function. PMID- 7865703 TI - Drug therapy and memory training programs: a double-blind randomized trial of general practice patients with age-associated memory impairment. AB - A double-blind randomized trial was performed involving 162 patients with age associated memory impairment (AAMI) selected and followed by their general practitioners. Two intervention methods--a drug and a cognitive therapy--were assessed in combination. Three randomized parallel groups of 54 patients each, aged 55 years and over, were followed and treated for 3 months. After a placebo wash-out period of 10 days, one group received 2.4 g of piracetam, another group, 4.8g, and the third, a placebo. A total of 135 patients, 45 in each group, completed the study. Combined therapy was most effective in patients whose baseline performance on memory tests was lowest. The best results were observed with 4.8 g of piracetam, especially when training sessions began after 6 weeks of drug treatment. This result was confirmed by the global impression of the principal investigator. PMID- 7865702 TI - Comparative performance of mildly impaired patients with Alzheimer's disease and multiple cerebral infarctions on tests of memory and functional capacity. AB - There is increasing evidence that mildly impaired patients with Alzheimer's disease (AD) may be distinguished from mildly impaired patients with multi infarct cognitive disorder (MICD) by their degree of semantic memory impairment. However, despite these observed group differences, it is unknown whether AD and MICD patients differ in their ability to perform a broad array of functional activities required for daily living and the degree to which severity of cognitive impairment is associated with functional deficits. Using a measure assessing numerous functional domains within the clinical setting, we were able to directly compare the functional capacity of mildly impaired AD and MICD patients, as well as a more cognitively impaired AD group. Although mildly impaired AD patients scored significantly lower on tests of semantic memory relative to their mildly impaired MICD counterparts, deficits in functional capacity were relatively equivalent. The AD group with more severe cognitive impairment scored lower on both memory and functional measures. A relatively high proportion of mildly impaired AD and MICD subjects evidenced impairment across a number of functional domains, suggesting that functional impairment may occur with relatively high frequency in these patient groups. PMID- 7865704 TI - On the paradox of improving sensitivity of ADL scales for the detection of behavioral changes in early dementia. PMID- 7865705 TI - Cost comparison of psychogeriatric consultations: outpatient versus home-based consultations. AB - In this article a cost-comparison study of psychogeriatric outpatient and home consultations (if all outpatients are seen at home) is reported. The cost of home visits was estimated to be less than that for outpatient consultations. The results are discussed in the context of methodological difficulties and the advantages and disadvantages of home and outpatient consultations. In view of the many advantages of home-based consultations, including lower costs, it is concluded that we should be developing and evaluating services with greater emphasis on home-based consultations. PMID- 7865706 TI - Geriatric rehabilitation in the United States and the Federal Republic of Germany: a comparison. AB - Similarities and differences in the way geriatric rehabilitation is viewed in the Federal Republic of Germany and in the United States are highlighted. The philosophy and goals of geriatric rehabilitation in both countries are basically similar. However, there are some differences, particularly in practice applications and in how the historical and social contexts of each country influence what is emphasized. This article traces the relevant knowledge components and practice application in each country and makes some comparisons. In addition, differences in how members of the geriatric team function are described, as well as the varying educational preparations of team members. Developments in both countries suggest that substantial integration of knowledge already has taken place. The continuation of this trend should bode well for the future. PMID- 7865707 TI - Patterns of psychogeriatric referral and attendance at three different settings in Hong Kong. AB - In order to analyze whether the referral system and nature of care exert any effect on the characteristics of patients, subjects aged 60 or above attending three medical centers on the Hong Kong Island between August and December 1990 were studied with respect to their age, sex, and psychiatric diagnosis. Psychiatric diagnoses were made in 98% of subjects at the psychogeriatric assessment service (PAC) (predominantly chronic organic brain syndrome), in 79.6% at the university psychiatric unit (mainly acute psychiatric problems, substance abuse, and deliberate self-harm), and in 20% at the general outpatient clinic (largely sleep and anxiety-related disorders). There was overrepresentation of the very old (above 80) and underutilization of counseling service at PAC. In Hong Kong, the psychogeriatric needs of the very old and of those with minor emotional disturbances associated with aging, retirement, and bereavement deserve reassessment. PMID- 7865709 TI - 3rd Commonwealth Conference on Diarrhoea and Malnutrition. Shatin, Hong Kong, 11 14 November 1994. Abstracts. PMID- 7865708 TI - Opportunities and challenges in international collaborative epidemiologic research of dementia and its subtypes: studies between Japan and the U.S. AB - Estimates of the prevalence rates for dementia vary significantly among countries. Such variation may be explained, at least in part, by methodologic differences in studies. The disparities in prevalence rates of dementia subtypes, particularly Alzheimer's disease and multi-infarct dementia, are especially apparent in studies conducted in Eastern and Western countries. In Japan and China, the prevalence of multi-infarct dementia exceeds that of Alzheimer's disease, whereas in the West, Alzheimer's disease predominates in the vast majority of studies. Clearly, cross-cultural studies of incidence using standard methods are needed to investigate whether a true difference in risk exists, and which risk factors differentially contribute to this variation. Migrant studies of genetically homogeneous populations offer a unique opportunity to answer these questions. This article explores the value of migrant studies, their application to etiologic questions of dementia and its subtypes, and recommendations concerning how to conduct such studies. PMID- 7865710 TI - Jejunal release of prostaglandin E2 in Crohn's disease: relation to disease activity and first-degree relatives. AB - Patients with Crohn's disease of the distal ileum show increased permeability to hyaluronan and increased release of histamine and complement components in uninvolved parts of the proximal jejunum. These abnormalities are related to disease activity, and are not found in first-degree relatives. Increased synthesis of prostaglandins has been observed in inflamed areas of the intestine in active Crohn's disease. Our purpose was to measure luminal prostaglandin release in patients with active and inactive Crohn's disease and their first degree relatives. Twenty-four patients with Crohn's disease of the distal ileum (10 in remission and 12 with inflammatory activity) and 17 of their first-degree relatives were included and compared with healthy control subjects (n = 39). Ten centimetres of the proximal jejunum was isolated between balloons as described previously and perfused with a balanced electrolyte glucose-containing solution. Luminal concentrations of PGE2 and albumin were measured and their luminal release was calculated. Luminal release of PGE2 was significantly higher in patients with Crohn's disease than in control subjects [69.7 +/- 11.5 and 34.0 +/ 4.7 pg/cm per h (3.7 +/- 0.6 and 1.8 +/- 0.3 ng/L), respectively, P < 0.01]. The PGE2 levels, however, were not positively correlated to disease activity. Furthermore, there was a modest, but significant increase in luminal PGE2 in first-degree relatives [53.6 +/- 7.0 pg/cm per h (2.9 +/- 0.4 ng/L), P < 0.05]. These changes were not accompanied by significant changes in luminal permeation of albumin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865711 TI - Sulfhydryl blocker-induced colitis in the rat: immunological changes in thymus gland and colonic mucosa. AB - The study was designed to examine the changes of thymus in sulfhydryl blocker induced colitis. We used N-ethylmaleimide (NEM) as sulfhydryl blockers. Fasted male Sprague-Dawley rats were given 3% NEM in 1% methyl cellulose into the colon. N-ethylmaleimide treatment caused severe diarrhoea with bleeding for the first 7 days. At autopsy, adhesions, colon dilatation, and single or multiple erosions and ulcers were observed. Time-course studies revealed that the lesions were most extensive and severe 3 or 7 days after the administration of NEM. Histological examination of colon on the 3rd day after NEM treatment demonstrated mucosal erosion, oedema and extensive infiltration of neutrophils. The mucosal lesions extended into the submucosa and muscle on the 7th day after NEM treatment. Immunohistochemical studies showed that T cells and macrophages were markedly increased in the lamina propria of colonic mucosa. After 3 weeks, the infiltration of chronic inflammatory cells was observed and regeneration of the mucosa was noticed. The thymus gland was significantly decreased in weight and size on the 3rd day after NEM treatment, but the weight loss of thymus gland was regained in 3 weeks. Transient atrophy of thymus gland was noticed in this colitis model. The phenotypes of thymocytes were not influenced by NEM treatment. It is concluded that the thymus abnormalities in human ulcerative colitis are not induced in this animal model and that other chronic models are necessary for the elucidation of the immunological abnormalities, including thymus abnormalities. PMID- 7865712 TI - Heterogeneous distribution of microcirculatory disturbance in the gastric mucosa during gastric hypercontraction in rats. AB - Gastric mucosal lesions induced by gastric hypermotility are characteristically observed along the gastric mucosal folds. To determine the role of microcirculatory disturbance in this particular condition, we measured the gastric mucosal haemodynamics after vagal stimulation and also examined histologically the transparent specimens of the transverse section of the contracted stomach in rats. Gastric mucosal haemodynamics measured with a reflectance spectrophotometer showed the repetition of ischaemia-reperfusion during gastric hypermotility. The rapidly frozen and transparent specimen of the corpus showed that gastric mucosa was stretched at the crest and compressed at the base of the mucosal folds. Characteristic distribution of red blood cells was observed; it was dense at the crest of the mucosal folds and sparse at the base. These results suggest that gastric hypermotility may induce the distinctive heterogeneous microcirculatory disturbance in the folds and may contribute to the characteristic localization of mucosal lesions. PMID- 7865713 TI - Stereospecific effects of tryptophan on gastric emptying and hunger in humans. AB - The amino acid tryptophan (tryp) is a potent inhibitor of gastric emptying in both animals and humans. Animal studies suggest that this effect may be specific for the L-enantiomer. The effects of D- and L-tryptophan on gastric emptying, intragastric distribution and appetite in humans were evaluated. Ten volunteers ingested 300 mL of either L-tryp (50 mmol/L), D-tryp (50 mmol/L) or normal saline labelled with 99mTc sulfur colloid on three occasions, separated by between 3 and 7 days. Hunger and fullness were measured with a visual analogue scale at -2, 15, 30 and 60 min after ingestion of each drink. Saline emptied faster from the stomach than both L-tryp and D-tryp (P < 0.05) and D-tryp emptied faster than L tryp (P < 0.005). Emptying from the proximal stomach was fastest for saline (P < 0.05) and faster for D-tryp than L-tryp (P < 0.005). Emptying from the distal stomach was faster for saline than both D- and L-tryp (P < 0.05). A reduction in hunger (P < 0.05) and a non-significant trend for an increase in fullness were observed after all three drinks. At 60 min, fullness was greater after L-tryp than after ingestion of D-tryp (P < 0.01). These observations indicate that the effect of tryptophan on gastric emptying in humans is stereospecific, consistent with the concept that stereospecific receptors for tryptophan exist in the human small intestine. PMID- 7865714 TI - Comparison of brush before biopsy, suction cytology, brush after biopsy and endoscopic biopsy in the diagnosis of carcinoma oesophagus. AB - A study was conducted on 40 patients of carcinoma oesophagus to compare the diagnostic yield of brush biopsy, suction cytology, brush after biopsy and endoscopic biopsy. The positive yield with brush before biopsy was 87.5%, with suction cytology 90%, with brush after biopsy 100% and with endoscopic biopsy 90%. Difference in the yield of brush after biopsy compared to other modalities was statistically insignificant (P > 0.05). However, the quantitative yield of the material was significantly high (P < 0.05) in the brush after biopsy compared to brush before biopsy. Of these three cytological modalities brush after biopsy appears to be the cytological technique of choice to be used as an adjunct to endoscopic biopsy. PMID- 7865715 TI - Clinical features in young adult patients with ischaemic colitis. AB - The clinical, radiographic and endoscopic findings in 16 patients with ischaemic colitis, all of whom were < 45 years of age, were analysed. The clinical features were characterized by an acute onset of abdominal pain and rectal bleeding, and persistent constipation prior to the onset of symptoms. Twelve of the 16 patients did not have any known predisposing factors. Barium enema examination and colonoscopy revealed longitudinal ulcers and oedema of the left side of the colon of these patients. These features were then compared with those found in patients with ischaemic colitis, who were > 70 years of age. Although the clinical symptoms, the site of involvement and the initial radiographic or endoscopic findings were similar between the two groups, the transient form of ischaemic colitis and constipation prior to the onset of symptoms were more frequently present in the young patients than in the old patients. These findings suggest that ischaemic colitis, which is not a rare condition even in young adults, is less severe in young patients than in old patients, and that constipation may be related to the pathogenesis of this disease in young adults. PMID- 7865716 TI - Enteroglucagon, but not CCK, plays an important role in pancreatic hyperplasia after proximal small bowel resection. AB - The present study was performed to examine the role played by pancreatotrophic factors, especially enteroglucagon and cholecystokinin (CCK), in the compensatory pancreatic hyperplasia observed after proximal small bowel resection (PSBR). Male Wistar rats were randomized into two groups, receiving either PSBR or transection (TRC). Five animals from each group were randomly selected for treatment with FK 480, a novel CCK antagonist. Four weeks after the operation, plasma levels of gastrin, CCK and enteroglucagon were measured. Pancreatic wet weight and protein, DNA, RNA and enzyme content were also determined. The wet weight and content of protein, DNA and RNA were significantly higher in PSBR rats than in TRC rats, regardless of whether they received FK-480. FK-480 had no suppressive effects on adaptive pancreatic growth after PSBR. Plasma enteroglucagon levels rose significantly in PSBR rats, and there were positive correlations between plasma enteroglucagon levels and pancreatic protein, DNA and RNA content. These findings demonstrated that plasma CCK was not the major trophic factor operating in the pancreas after PSBR, and showed that enteroglucagon plays an important role in the pancreatic hyperplasia that occurs after PSBR. PMID- 7865717 TI - Correlation of serum HCV RNA and alanine aminotransferase levels in chronic hepatitis C patients during treatment with ribavirin. AB - To evaluate the effect of ribavirin on serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels, 22 patients with chronic HCV infection were treated with oral ribavirin 1200 mg daily in three divided doses for 4 weeks. At the end of 4 weeks treatment, the serum ALT decreased in all but one patient and became normal in three individuals. The mean pretreatment serum ALT was reduced significantly from 193 +/- 45 i.u./L to 95 +/- 16 i.u./L after 4 weeks therapy (P = 0.009). However, 8 weeks after cessation of treatment, the serum ALT rose to a mean value of 154 +/- 21 i.u./L. The mean pretreatment serum HCV RNA was not significantly decreased at the end of 4 weeks treatment (7.0 x 10(5) vs. 4.1 x 10(5) copies/mL, P > 0.05). However, serum HCV RNA levels were decreased in 12 and increased in 10 patients at the end of 4 weeks therapy. Eight weeks after cessation of therapy, the serum HCV RNA of 22 patients rose to a mean value of 4.9 +/- 10(5) copies/mL. Six patients who continued to have elevated serum ALT and positive HCV RNA after the initial 4 weeks treatment received oral ribavirin at the same dosage for an additional 24 weeks. The serum ALT again decreased in all six patients during therapy, but rose to pretreatment values by 8 weeks after cessation of the treatment. In addition, no significant changes were noted in the mean serum HCV RNA levels during and after 24 weeks of ribavirin therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865718 TI - Total paracentesis in non-alcoholic cirrhotics with massive ascites: mid-term effects on systemic and hepatic haemodynamics and renal function. AB - Single total paracentesis (4.8-11 L) was performed in 23 patients with hepatitis B surface antigen (HBsAg)-positive cirrhosis and massive ascites and its effects on systemic and hepatic haemodynamics and renal function were examined over 5 days. Severe hypotension occurred in six (26.1%) patients from 6 to 54 h after paracentesis. In the remaining 17 patients, compared to the baseline, there was an increase in the cardiac output (6.1 +/- 0.3 vs 6.7 +/- 0.3 L/min, P < 0.001) and a decrease in right atrial pressure (8.8 +/- 0.8 vs 4.3 +/- 0.7 mmHg, P < 0.001), systemic vascular resistance (1160 +/- 61 vs 976 +/- 50 dyne.s.cm-5, P < 0.001), and wedged hepatic venous pressure 30 min after completion of paracentesis. After 5 days, right atrial pressure, systemic vascular resistance and wedged hepatic venous pressure returned to baseline, while the cardiac output dropped to a level lower than the baseline (5.7 +/- 0.7 L/min, P < 0.05). Hepatic venous pressure gradient had returned to baseline after 5 days. Serial tests of serum creatinine level showed an increase from day 3 (1.34 +/- 0.14 vs 1.04 +/- 0.10 mg/dL, P < 0.05). On day 5, creatinine clearance (55.7 +/- 5.4 vs 41.9 +/- 5.3 mL/min, P < 0.05) and effective renal plasma flow (351 +/- 32 vs 293 +/- 29 mL/min, P < 0.05) were decreased, compared to the baseline. Based on these data, infusion of a volume expander may be necessary for total paracentesis to avoid systemic haemodynamic complications in non-alcoholic cirrhosis. PMID- 7865719 TI - An early gallstone clearance following repeat piezoelectric lithotripsy. AB - Piezoelectric extracorporeal litotripsy was performed in 128 symptomatic patients with radiolucent gall-bladder stones to assess the significance of disintegration in fragment clearance. Up to 10 repeat lithotripsy sessions were scheduled to achieve a fragment target size of < 3 mm. Fragmentation assessed by the size of the largest fragments after the last session was graded into three classes. I: sludge-like disintegration, 18%; II: < 3 mm (mean +/- s.d., 1.7 +/- 0.5 mm), 56%; and III: > or = 3 mm (3.3 +/- 0.6), 26%. All patients were initially subjected to lithotripsy alone. Bile acid dissolution therapy was started only when ultrasonography failed to show the evidence of decrease in the < 3 mm fragments during a 1 month follow up. Finally, 69 patients (54%) were treated by lithotripsy alone, and the remaining 59 received additional dissolution therapy at a mean period of 2.5 months after the initial lithotripsy. The rate of complete clearance in class I, II and III patients was 91, 42 and 10% at 6 months and 100, 68 and 49% at 18 months, respectively. Significant differences were noted between the three fragmentation grades (I vs II, III, P < 0.0001; II vs III, P < 0.02). The patients with complete clearance within 6 months were seen only in those treated by lithotripsy alone, while the majority (87%) of patients with complete clearance during the later period were seen in those treated by additional dissolution therapy. We conclude that a high degree of fragmentation appears to lead stones to an earlier period clearance, and reduce the need for dissolution therapy. PMID- 7865720 TI - Interstitial tumour cell invasion in small hepatocellular carcinoma. Evaluation in microscopic and low magnification views. AB - In order to study the process of hepatocellular carcinoma (HCC) development, and to search for a clue to histologic diagnosis of well-differentiated HCC (wd-HCC), interstitial invasion in small HCC was evaluated. The study material consisted of 35 cases of HCC that were smaller than 3 cm that comprised 17 cases of wd-HCC, 18 cases of moderately or poorly differentiated classical HCC (cl-HCC), and 20 cases of large regenerative nodules (LRN). Interstitial invasion was microscopically classified into three patterns: (i) crossing type, in which HCC was invading across fibrous septa of tumour nodules; (ii) longitudinal type, in which tumour cells were growing longitudinally within fibrous septa; and (iii) irregular type, in which the portal area was irregularly invaded by HCC. The crossing type was found in two cases (12%) of wd-HCC and 10 cases (56%) of cl-HCC while the longitudinal type was observed in 16 cases (94%) of wd-HCC and eight cases (44%) of cl-HCC. The irregular type was frequently seen in wd-HCC (15 cases, 88%), and cl-HCC (12 cases, 67%). No interstitial invasion was observed in LRN. Interstitial invasion could be recognized even in the low magnification view of histological specimens, with a detection rate of 59% (10 cases) in wd-HCC and 72% (13 cases) in cl-HCC. These results suggest that evaluation of interstitial invasion is useful in diagnosing wd-HCC independent of cellular atypia. In addition, such invasive growth is revealed to play an important role in destroying original hepatic architecture during its developmental process from the early to advanced stages. PMID- 7865721 TI - Effect of hepatocyte volume on energy status in the cirrhotic rat liver. AB - To evaluate the effect of reduced hepatocyte volume on liver energy status, the relationship between the morphologically quantified hepatocyte volume and biochemical parameters, and the difference in nuclear density between the parenchyma and stroma were assessed in rat livers with thioacetamide-induced cirrhosis. The ratio of hepatocytes to whole liver tissue, defined as the 'hepatocyte area ratio', and the nuclear densities of the parenchyma and stroma were calculated microscopically with an image analysing system. Adenine nucleotide, protein and DNA contents, and the ornithine carbamoyltransferase activity in the liver were assayed. In the cirrhotic group, adenine nucleotide content, protein content and ornithine carbamoyltransferase activity were positively correlated with the hepatocyte area ratio, whereas DNA content was negatively correlated with this ratio. The adenylate energy charge of the cirrhotic liver was maintained at a constant level regardless of the ratio. Adenine nucleotide content, protein content and ornithine carbamoyltransferase activity per fractional 'hepatocyte area ratio' in cirrhotic livers were significantly lower than in control livers. The nuclear density of the stroma was significantly greater than that of the parenchyma. These results suggest that the lowered energy status in the cirrhotic liver is not caused by reduced hepatocyte volume but rather by impaired hepatocyte metabolism. In addition, the morphological measurement with an image analysing system was found to be useful for evaluating the effects of decreased hepatocyte volume on biochemical derangements in cirrhotic tissue. PMID- 7865722 TI - Hepatology: current status and problems in the USA and Canada. PMID- 7865723 TI - Hepatology training in the United States. PMID- 7865724 TI - Hepatology in Australia. PMID- 7865725 TI - Hepatology, education and research: South Africa. PMID- 7865727 TI - The current state of hepatic surgery and its future prospects. PMID- 7865726 TI - Hepatology research and education in Japan. PMID- 7865728 TI - Blood flow, contractions and ischaemia-reperfusion: a possible pathogenetic mechanism for ulcers. PMID- 7865729 TI - Rise and fall of the Plummer-Vinson syndrome. AB - Three hypotheses have been proposed for the decreased incidence of Plummer-Vinson disease: non-existence, identity with inlet gastric mucosa of the oesophagus and disappearance of the predisposing condition(s). We examined these possibilities by reviewing our understanding of the syndrome. The early framers disagreed on the cause, but many thought it was a precursor for upper oesophageal carcinoma. Four explanations arose to account for the pathogenesis: iron deficiency; nutritional deficits; autoimmunity; and gastric lesion. We believe the decline in recognition paralleled the improve of dietary status and the treatment of sideropenic anaemia with inorganic iron salts. PMID- 7865730 TI - Oesophageal perforation following endoscopic variceal ligation and balloon tamponade. AB - Endoscopic variceal ligation (EVL) related complication is rarely reported. A case is presented of a 74 year old man with oesophageal variceal bleeding who developed oesophageal perforation following EVL and balloon tamponade. An oesophageal wall defect was induced by EVL and tissue repair was hindered by decompensated liver reserve and shock status; concomitant balloon tamponade precipitated oesophageal perforation. The case is reported to draw attention to oesophageal perforation after concurrent use of balloon tamponade and EVL. PMID- 7865731 TI - High prevalence of duodenal ulcer in Indochinese immigrants attending an Australian university hospital. PMID- 7865732 TI - Identifying IEG target genes in vivo. PMID- 7865733 TI - Proline clustering in proteins from synaptic vesicles. AB - Synaptic vesicle proteins share a specialized and common fate throughout the life cycle of the vesicle, and thus may need to respond to some common signals. It is therefore expected that these proteins will share some common motifs. However, sequence comparison among many of these proteins has not revealed any obvious motifs. Such a motif may be formed by the relative abundance of proline residues, which are not randomly distributed along the sequence but rather are clustered at the cytoplasmatic face of vesicular proteins. We propose that proline clusters serve as structural spacers between functional domains as well as potential target sites for protein-protein interactions. In view of the proline-rich nature of SH3 binding proteins, some of the proline-rich synaptic vesicle proteins may also participate in SH3 binding. Such binding may modulate certain signalling pathways in nerve terminals. Surprisingly, the consensus sequence between the proline clusters of synaptic vesicle proteins is found in a large family of abundant proline-rich proteins of the secretory organelles of the parotid exocrine gland. PMID- 7865734 TI - Calciproteins regulate cyclic AMP content and melatonin secretion in trout pineal photoreceptors. AB - Photoreceptor cells of the fish pineal transduce photoperiodic information into the rhythmic secretion of melatonin. The nocturnal rise in melatonin secretion has been associated with an increase in cyclic AMP (cAMP) production and with an entry of Ca2+ ions through L-type voltage-dependent channels. It is shown here that two inhibitors of calciproteins, W7 and calmidazolium, inhibit melatonin secretion and, to a lesser extent, cAMP levels in cultured trout pineal photoreceptors. Kinetic studies indicated that melatonin secretion was affected earlier than cAMP in cells cultured in the presence of W7. The present results provide evidence that Ca2+ acts through one or more calciproteins to regulate melatonin production. It is suggested that Ca2+/calciprotein complexes might act at two different sites, one involving regulation of cAMP metabolism, and the other being independent from cAMP. PMID- 7865735 TI - Chronic neonatal NMDA blockade results in long-term cholinergic increase in the rat spinal cord. AB - Rat pups were treated daily with increasing doses of the competitive N-methyl-D aspartate (NMDA) antagonist CGP 39551 from postnatal day 1 to 22. Normal rats, as well as rats kept undernourished to the same extent as CGP 39551-treated animals were raised in parallel. The neonatal treatment resulted in significant increase of choline acetyltransferase (+14%) in the adult spinal cord. High affinity glutamate uptake was increased to a similar magnitude in treated rats, but the same effect was also noticed for neonatally undernourished rats. No alteration of other neurochemical markers was observed. The present results add new evidence to a developmental role mediated by NMDA receptors and extend to the spinal cord the value of models of chronic neonatal block of this receptor. PMID- 7865736 TI - A zinc-containing fiber system of thalamic origin. AB - Zinc-containing neurons are cells that sequester zinc presynaptically and release it when active. Previously such neurons have been found almost exclusively in cerebrocortical and amygdalar regions. Here we describe a thalamo-cortical pathway that is zinc-containing, namely, the projection from the anterodorsal nucleus of the thalamus to the subicular cortex. The pathway was identified by the zinc-specific retrograde transport methods; its addition to the zinc containing cerebral circuitry reinforces the association of the zinc-containing terminals with cortico-limbic systems. PMID- 7865737 TI - Ultrastructural distribution of NADPH-diaphorase in cortical synapses. AB - To elucidate the role of nitric oxide (NO) in synaptic structures, the ultrastructural localization of the enzyme NO synthase (NOS), based on the cytochemical NADPH-diaphorase staining, was studied in neocortical and hippocampal neuropil areas. For the localization of NADPH-diaphorase activity a special tetrazolium salt (BSPT) was applied. BSPT-formazan, the osmiophilic reaction product, was found to be attached to endomembranes, predominantly the endoplasmic reticulum. Quantitative studies on synaptic regions revealed that mainly presynaptic areas (41% in hippocampus, 38% in neocortex) showed labelling. Postsynaptic regions were only exceptionally labelled by BSPT-formazan (3% in hippocampus, 5% in neocortex). The present findings support the view that NO may be involved in diverse synaptic functions acting preferentially from the presynaptic side. PMID- 7865738 TI - Time-slice analysis of inhibition in cat striate cortical neurones. AB - A prominent feature of visual cortical neurones is orientation specificity. The underlying mechanisms and the possible contributions of intracortical inhibition are continuously the subject of intense debate. We analysed orientation tuning in relation to time after stimulus onset and the effects of blockade of GABAergic inhibition with microiontophoretically applied bicuculline in single cells in area 17. The majority of the cells had sharp and temporally stable orientation specificity; however, changes of receptive field structure, widening of orientation tuning and changes in preferred orientation were observed between 30 and 150 ms after stimulus onset when inhibition was blocked. This indicates that under normal conditions in most in most striate cortical cells intracortical inhibition sculptures receptive field structure and keeps orientation tuning narrow and constant in time. PMID- 7865739 TI - Regulation of basal release of GABA by noradrenaline in the kitten visual cortex. AB - To determine the modulatory effect of noradrenaline (NA) on basal release of gamma-aminobutyric acid (GABA), we measured the extracellular GABA with a brain microdialysis technique in the kitten visual cortex. Local infusion of NA through a cannula, which was implanted 2 mm away from the dialysis probe, gave rise to a marked increase in GABA release. This NA-induced GABA release was suppressed by tetrodotoxin, a sodium channel blocker, which was perfused at the probe site. The effect of NA was antagonized by pretreatment with metoprolol, a beta 1-selective antagonist. These results suggest that the cortical noradrenergic system may be involved in the regulation of basal GABA release that is possibly due to the activity of inhibitory neurones in the kitten visual cortex. PMID- 7865740 TI - Antibodies to nerve growth factor (NGF) prolong the sensitive period for monocular deprivation in the rat. AB - Neural plasticity in the visual cortex, as tested by changes in its functional organization induced by monocular deprivation (MD), is present only during a restricted period of postnatal development (critical period). To investigate whether this process of synapse strengthening depends upon NGF, we antagonized endogenous NGF during the critical period by implanting anti-NGF producing cells. Anti-NGF treated and control rats were monocularly deprived after the end of the critical period. In anti-NGF treated but not in control rats MD was still effective. We conclude that antagonism of endogenous NGF prolongs the critical period, possibly by delaying the process of synapse consolidation in the visual cortex. PMID- 7865741 TI - Place cells in the ventral hippocampus of rats. AB - Many cells recorded from the dorsal hippocampus of freely moving rats are intensely active only when the rat's head is in a particular part of its environment. For this reason, such units are called 'place cells'. We have investigated whether place cells are also found in the ventral hippocampus. Recordings were made from ventral hippocampal units while rats chased food pellets in a cylindrical arena. The rat's position was simultaneously recorded by tracking a light on the rat's head. Our data show the existence of cells in the ventral hippocampus whose positional firing patterns and electrophysiological properties are very similar to those of dorsal hippocampal place cells. PMID- 7865742 TI - Roles of endogenous nitric oxide in cerebellar cortical development in slice cultures. AB - Using the slice culture system for 9-day-old rat cerebellum, roles of nitric oxide (NO) in the cerebellar cortical development were examined. Granule cell migration was inhibited by N-nitro-L-arginine (L-NNA) and by haemoglobin (Hb), but not by N-nitro-D-arginine (D-NNA), added to the culture medium, showing that NO-mediated transmission is involved in some process for granule cell migration. Furthermore, immunohistochemical analysis revealed that the cessation of granule cell proliferation and the differentiation of Bergmann glia were inhibited in the presence of L-NNA and Hb. These results suggest that endogenous NO can be a signal for the differentiation of granule cells and Bergmann glia in cerebellar cortical development. PMID- 7865743 TI - Magnetic resonance axonography of the rat spinal cord. AB - In spite of dramatic advancement in biomedical imaging technologies, non-invasive visualization of anatomic detail of the spinal cord has remained a major challenge. Here, a novel color-coded contrast method for magnetic resonance imaging (MRI) which provides superb resolution of the spinal cord in live animals, comparable to that of histological preparations, is described. The method, referred to here as three dimensional anisotropy (3DAC) contrast MRI, displays cross-sectional images in the full visible color spectrum, encoding directional information regarding intravoxel anisotropic water motion in space. Since neuronal fibers, especially axons, possess significantly higher intravoxel anisotropic water motion compared with other elements in the nervous system, 3DAC is highly sensitive to axonal direction and density. Axonography of the spinal cord of rats obtained using this technique showed anatomic detail at a resolution hitherto unobtainable in live animals. PMID- 7865744 TI - Mouse cortical cells lacking cellular PrP survive in culture with a neurotoxic PrP fragment. AB - To elucidate whether the neurotoxic effect of a prion protein fragment (PrP106 126) is in some way mediated by the cellular isoform of the prion protein (PrPC), dissociated cortical cell cultures were prepared from mice in which the PrP gene had been disrupted (PrP0/0 mice). Cell survival after 10 days in culture was tested with an MTT assay. PrP106-126 applied every second day for 10 days in cultures from normal mice resulted in the death of 34% more cells than in untreated cells. When PrP106-126 was applied to cultures from mice lacking PrPC expression, survival was equal to or greater than that of untreated control cells. These results support the notion that expression of PrPC is required for the neurotoxic effect of PrP106-126. PMID- 7865745 TI - Computer-assisted shock-reinforced Y-maze training: a method for studying spatial alternation behaviour. AB - Y-mazes are widely used for discrimination learning and spatial alternation tasks. We present here a computer-assisted Y-maze model for spatial alternation learning via footshock reinforcement. No intramaze cues are provided and handling between trials is no longer required. Pretraining application of scopolamine (1 mg kg-1) and D-AP5 (2-amino-5-phosphonopentanoate; 0.016 mg) clearly impairs acquisition and retention (tested 24 h after acquisition) of spatial alternation. These effects are not due to state-dependent changes caused by drug treatment. Similar results were reported by others in food-motivated spatial alternation tasks as well as spontaneous alternation paradigms. The data support our model as a useful tool for studying spatial alternation in the Y-maze. PMID- 7865746 TI - Habituation of acoustic startle in rats--a functional ablation study. AB - Data from lesion studies data indicate that the removal of the medial cerebellum prevents acquisition but not retention of long-term habituation (LTH) of the acoustic startle response (ASR). The spreading depression (SD) of the vermis was used to examine under more functional conditions the build-up of LTH of the ASR in Wistar rats. Our findings showed that reversible blockade of the vermis during training disrupted LTH of the ASR without changing within-trials habituation. In contrast to previous data, the present results suggest that SD strongly affects the amplitude of the startle response. The data are discussed in respect to a role of the vermis in the control of emotional behaviour in animals. PMID- 7865747 TI - Induction of LTP and LTD in visual cortex neurones by intracellular tetanization. AB - Neurones from supragranular layers of rat visual cortex slices were activated by intracellular tetanization (IT) without concomitant presynaptic stimulation. The effect of IT was examined on EPSPs evoked at low stimulation intensity from two subsets of afferents by electrodes positioned in layers II and IV, respectively. In 17 of 23 inputs to 15 cells IT led to changes in EPSP amplitudes which persisted throughout the recording period (from at least 40 min to 3 h). For 10 potentiated inputs (nine cells) and eight depressed inputs (seven cells), EPSP amplitudes measured 30 min after tetanization were 167 +/- 14% and 55 +/- 14% of the pretetanic controls, respectively. In seven cells both inputs changed, in five cases modifications were of the opposite and in two cases of the same polarity. PMID- 7865748 TI - Role of caffeine-sensitive Ca2+ stores in Ca2+ signal termination in adult mouse DRG neurones. AB - The role of calcium stores in cytoplasmic calcium signal termination was studied in acutely isolated small and large DRG neurones from mice. Cytoplasmic calcium concentration ([Ca2+]in) was recorded using indo-1 microfluorometry and membrane potential was monitored by 'perforated' whole-cell patch-clamp. Depolarization induced [Ca2+]in transients recovered significantly faster in large neurones than in small neurones. Caffeine was able to release Ca2+ from internal stores only in large neurones, while small neurones lacked caffeine-releasable calcium stores. Thapsigargin abolished caffeine-induced Ca2+ release and significantly slowed down recovery of depolarization-triggered [Ca2+]in transients in large neurones. We conclude that [Ca2+]in signals recover faster in large DRG neurones, at least in part due to the higher rate of Ca2+ sequestration by intracellular stores. PMID- 7865749 TI - M and P retinal ganglion cells of diurnal and nocturnal New-World monkeys. AB - M and P retinal ganglion cell morphology revealed by biocytin retrograde labelling was compared in two closely related New-World monkeys, Cebus and Aotus, to investigate whether nocturnal and diurnal species of primates have similar cell classes. Monkey and cat ganglion cells from regions of matching cell class densities were also compared. Cat alpha, cat beta, Aotus M, and Cebus M cells were similar in many aspects, but Cebus M cells had higher branching density. Cebus and Aotus P cells formed a distinct group and represent a primate specialization common to diurnal and nocturnal simians. PMID- 7865750 TI - Endogenous phosphorylation of tau proteins in brain slices. AB - Tau protein phosphorylation has been implicated as a main process that regulates microtubule dynamics. A large number of tau isoforms is generated by phosphorylation through the action of a diversity of kinases. We have analysed variations in tau phosphorylation by two-dimensional gel electrophoresis, where a great heterogeneity of isoforms can be detected. Using mouse brain slices from various developmental stages we have found preferential phosphorylation of low molecular weight tau isoforms in all the ages analysed. A greater isoform diversity was found in juvenile than in adult brain. Brain slices provide a tightly regulated environment that preserves cell compartmentalization and has shown to be very useful for studies on tau phosphorylation. PMID- 7865751 TI - NGF-response of EGF-dependent progenitor cells obtained from human sympathetic ganglia. AB - Signalling molecules are thought to play a significant role in determining the fate of neural crest progenitor cells. The human sympathetic chain was identified at 6.5, 7.5, 8.2, 10.2 and 11.4 postconception (PC) weeks demonstrating low affinity nerve growth factor (NGF) receptors, and was processed for tissue culture. In the presence of epidermal growth factor (EGF), floating spheres of proliferating progenitor cells were developed in vitro. In the absence of EGF progenitor cells differentiated into tyrosine hydroxylase (TH)-immunoreactive neuronal and TH-negative flat cells. NGF treatment significantly increased neurite outgrowth and survival of TH-immunoreactive cells. The multipotent cells we isolated differ from previously reported sympathoadrenal progenitors in that they give rise to TH immunoreactive neurones precociously sensitive to NGF. PMID- 7865752 TI - Differential effect of NGF and EGF on ERK in neuronally differentiated PC12 cells. AB - The purpose of this study was to examine ERK enzymatic activity after neuronal differentiation and to determine if the intracellular enzyme continues to be responsive to changes in extracellular NGF. The results demonstrate that long term NGF maintains ERK activity above normal resting levels, but that it is also greatly reduced from that achieved rapidly after NGF stimulation. Withdrawal of NGF reduces ERK activity further. Re-stimulation of the enzyme by readdition of NGF after NGF withdrawal results in a 10-fold increase in activity. Withdrawal and readdition of EGF is without such a marked effect. The ability of ERK to respond to changes in NGF after neuronal differentiation indicates that this enzyme may serve important functions in addition to the induction of the neuronal phenotype. PMID- 7865753 TI - Intracranial metyrapone stimulates CRF-ACTH axis in the teleost, Clarias batrachus: possible role of neurosteroids. AB - Intracranial administration of metyrapone, a blocker of the enzyme 11-beta hydroxylase, which is essential for the biosynthesis of corticosteroids, resulted in profound stimulation of the nucleus preopticus and the CRF-ACTH axis in the teleost, Clarias batrachus. It is suggested that the putative blockade of the neurosteroid biosynthesis following metyrapone might be responsible for this action. The present study for the first time uncovers the possibility of inhibitory regulation of the CRF-ACTH axis by metyrapone sensitive neurosteroids. PMID- 7865754 TI - Calretinin labels a specific neuronal subpopulation in primate globus pallidus. AB - All pallidal neurones are believed to share the same chemical and morphological phenotype in primates. At variance with this idea is the present finding that calretinin (CR), a calcium binding protein, occurs only in a subset of pallidal neurones in squirrel monkeys. This chemospecific subpopulation comprises both large and small bipolar and multipolar neurones distributed according to a rostrocaudal decreasing gradient. The large neurones outnumber small neurones throughout the pallidum; they abound principally in the external pallidal segment, whereas the small neurones prevail in the internal segment. Some pallidal CR-positive neurones display dorsoventrally elongated dendrites, while others show dendrites radiating in all directions. These findings reveal that pallidal neurones form a chemically and morphologically heterogeneous population in primates. PMID- 7865755 TI - NK1 and NK2 receptors contribute to C-fibre evoked slow potentials in the spinal cord. AB - Small diameter primary afferents produce slow synaptic potentials in spinal neurones. These can be recorded as prolonged ventral root potentials (VRPs) in the isolated neonatal rat spinal cord preparation. The VRP elicited by stimulating C-fibres consists of two phases: an early phase comprising a monosynaptic and a short polysynaptic response identical to that elicited by low threshold A beta fibres and a late phase which has an initial component (0.1-1 s) which is sensitive to N-methyl-D-aspartic acid receptor antagonism and a very long lasting second component (1-20 s) which is resistant to these antagonists. We now demonstrate that the slowest component of the VRP is significantly reduced by both NK1 and NK2 tachykinin receptor antagonists and as a consequence, tachykinins have a particular contribution to the cumulative depolarization produced by low frequency (1 Hz) C-fibre stimulation. PMID- 7865756 TI - AMPA/KA receptor induced AP-1 DNA binding activity in cultured Bergmann glia cells. AB - The effect of L-glutamate (L-Glu) and its structural analogs kainate (KA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) on the DNA binding activity of the activator protein 1 (AP-1) family of transcription factors was examined in cultured chick cerebellar Bergmann glia cells. These agonists evoked a dose- and time-dependent increase in AP-1 DNA binding activity and their responses were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The increase in DNA binding is probably mediated by an AMPA/low affinity KA subtype of L-Glu receptor. The synaptic localization of these receptors, their ion channel properties and a stimulus-transcription coupling further strengthen the putative role of glia cells in the modulation of synaptic efficacy and plasticity. PMID- 7865757 TI - Lack of direct action of D-fenfluramine on arcuate preproNPY mRNA levels in the rat. AB - Hypothalamic neuropeptide Y (NPY) and 5-hydroxytryptamine (5-HT) may interact to regulate food intake. This study investigated the effects of the 5-HT reuptake blocker and secretagogue D-fenfluramine (D-FEN) on preproNPY mRNA abundance in the hypothalamic arcuate nucleus (ARC) of free-feeding and food-deprived (FD) rats in two treatment regimens. ARC preproNPY mRNA levels were significantly increased in FD rats, to the same extent as in combined FD/D-FEN animals. D-FEN treatments producing different-sized reductions in food intake (and body weight) produced corresponding changes in ARC preproNPY mRNA abundance. These findings suggest that ARC preproNPY mRNA levels are not directly altered by D-FEN, and that D-FEN-induced anorexia does not involve effects on the hypothalamic NPY system at the level of NPY gene transcription. PMID- 7865758 TI - Monoclonal antibody to the C-terminus of beta-amyloid. AB - Soluble amyloid beta-protein (A beta) is normally produced, but forms deposits in the brain of Alzheimer's (AD) patients. The length of isolated A beta in SDS insoluble amyloid from AD brain is reported to vary between plaques and vessels ranging from 28 to 43, with major species being 40 and 42 residues. Because the A beta C-terminus determines aggregation rates, we made an A beta monoclonal antibody distinguishing beta 1-42 from beta 1-40. In AD cortex, the beta 1-42 antibody recognizes all the structures identified by monoclonal to beta 1-40 on adjacent sections: plaque cores, diffuse A beta deposits and vascular amyloid. These antibodies help define variation in A beta length between different deposits, regions and autopsied brains. PMID- 7865759 TI - 25-Hydroxycholesterol induces reorganization of lysosomes in normal but not Niemann-Pick disease type C astrocytes. AB - 25-hydroxycholesterol (25-OHC), an oxysterol that potently regulates cellular cholesterol metabolism, induced formation of novel fibrillar structures in normal mouse astrocytes as observed by fluorescence microscopy with the cholesterol probe, filipin. These fibrils were identified as lysosomes by their immunoreactivity for the lysosome associated membrane glycoprotein (LAMP). In contrast, astrocytes derived from the Niemann-Pick disease type C (NPC) mutant mouse were resistant to this oxysterol-induced lysosomal reorganization. NPC astrocytes have abnormal intracellular cholesterol storage as observed by brightly positive filipin staining of their lysosomes. These results show that lysosomal cholesterol storage in NPC astrocytes is associated with a block in oxysterol-mediated fibrillar reorganization of lysosomes. PMID- 7865760 TI - Benzodiazepines modulate calcium spikes in young and adult hippocampal cells. AB - GABAA receptor-independent effects of benzodiazepine receptor (BZ-R) agonists on calcium and barium spikes were recorded intracellularly in the presence of bicuculline from CA3 hippocampal cells of young and adult rats. Zolpidem (omega 1 BZ-R agonist), had no effects in young animals but decreased calcium and barium spikes and barium currents in adults. Midazolam (omega 1 and omega 2 BZ-R agonist) increased barium spikes in both young and adult animals. The effects on calcium spikes were more complex since a decrease was sometimes preceded by an increase. Thus, in adults zolpidem acting on omega 1 BZ-R reduced calcium influx while in young rats midazolam acting on omega 2 BZ-R increased barium influx. This modulation of calcium spikes by benzodiazepines could be relevant of calcium spikes by benzodiazepines could be relevant because of the developmental role played by calcium dependent processes. PMID- 7865761 TI - Increase of ATP levels by glutamate antagonists is unrelated to neuroprotection. AB - Succinic dehydrogenase in mouse cortical explant cultures was inhibited by 3 nitropropionic acid (3-NPA). ATP concentrations declined upon application of 3 NPA. At 4 h, ATP levels of cultures treated with 3-NPA alone were no different from those in cultures treated additionally with MK-801 (20 microM), 6-cyano-7 nitroquinoxaline-2,3-dione (CNQX; 10 microM) or a combination thereof. However, MK-801 and MK-801 plus CNQX mitigated morphological lesions caused by 3-NPA. CNQX alone did not influence the extent of morphological damage. In conclusion, MK 801, at concentrations which were neuroprotective against 3-NPA lesions in cortical explant cultures, did not modify 3-NPA dependent decreases in cellular ATP levels. These data indicate that the neuroprotective effects of glutamate receptor antagonists in this model are probably receptor mediated and do not involve effects on cellular metabolism. PMID- 7865762 TI - Characterization of muscarinic receptors involved in tracheal CGRP release. AB - Application of acetylcholine (ACh) to isolated rat trachea induces an increase in calcitonin gene-related peptide (CGRP) outflow in the perfusates. The elevation of CGRP release by ACh was absent in capsaicin-desensitized preparations, suggesting that the release of peptide is derived from capsaicin-sensitive afferent nerves. ACh-induced release was not altered by hexamethonium, but was significantly attenuated by atropine, indicating involvement of the muscarinic receptor. Effects of three selective muscarinic subtype antagonists, pirenzepine (M1), methoctramine (M2) and 4-DAMP (M3) on ACh-evoked release were examined. The ordering of antagonist potency was: 4-DAMP (ED50 = 14 nM) > pirenzepine (3.8 microM) > methoctramine (> 10 microM). The results suggest that the muscarinic receptor mediating tracheal CGRP release resembles the M3 receptor subtype. PMID- 7865763 TI - Striatal changes in preproenkephalin mRNA levels in parkinsonian monkeys. AB - Levels of preproenkephalin (PPE) mRNA were measured in different sectors of the striatum with in situ hybridization histochemistry in both normal and parkinsonian (MPTP-treated) squirrel monkeys. In parkinsonian monkeys, a marked increase in PPE mRNA levels was noted in the dorsolateral third of the precommissural putamen and in most of the postcommissural putamen. These regions largely correspond to the sensorimotor striatal territory. The other striatal sectors, including the caudate nucleus, did not exhibit significant changes, despite the fact that the loss of the dopaminergic input was severe in most of the striatum. These results reveal that PPE mRNA expression is specifically altered in striatal regions involved in sensorimotor processing in parkinsonian monkeys. PMID- 7865765 TI - Tolbutamide suppresses slow and medium afterhyperpolarization in hippocampal slices. AB - Afterhyperpolarizations (AHPs) were recorded (in whole-cell mode, with KMeSO4 containing electrodes) after multiple spikes evoked with 200 ms current pulses. Bath applications of tolbutamide (0.5-1 mM) to 12 CA1 neurones nearly abolished the medium and slow component of AHPs. Thus the AHPs generated by 7-8 spikes (mostly) were reduced by 82.6 +/- 5.2% (s.e.m.) at the initial peak (mAHP) and by 85.0 +/- 5.8% 1 s later (sAHP). Glibenclamide (10 microM) had no comparable blocking effect. The previous finding that tolbutamide (but not glibenclamide) selectively suppresses the anoxic hyperpolarization of CA1 neurones is therefore consistent with the idea that the anoxic hyperpolarization is mediated by Ca dependent (especially AHP-type) K channels. PMID- 7865764 TI - Decreased excitotoxic sensitivity in the olfactory cortex of adult rats after neonatal NMDA blockade. AB - Neonatal rats were daily treated with increasing doses of the competitive NMDA antagonist CGP 39551 from postnatal day 1 to 22. At 75-80 days of age the rats were given an excitotoxic dose of kainic acid s.c. Histological examination suggested that the olfactory cortex of the neonatally CGP 39551-treated rats was less damaged than that of controls. This was quantitatively confirmed by assaying the decrease of appropriate neurochemical markers (D-[3H]aspartate uptake and glutamate decarboxylase) as an index of the extent of neuronal degeneration. By contrast, the decrease of the same markers was not different in the hippocampus. These results suggest a selective effect on some brain circuits of adult rats consequent to the neonatal blockade of NMDA receptors and, therefore, add new evidence to a developmental role of this receptor. PMID- 7865766 TI - Riluzole and experimental parkinsonism: partial antagonism of MPP(+)-induced increase in striatal extracellular dopamine in rats in vivo. AB - Superfusion of the rat striatum with 100 microM of 1-methyl-4-phenylpyridinium (MPP+) induced a 70-fold increase in dopamine (DA) release and a decrease in the extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Pretreatment with riluzole (8 mg kg-1, i.p.), a compound that interferes with glutamatergic transmission, partially antagonized the effect of MPP+ on the release of DA, but did not change the effects of this toxin on the efflux of DOPAC and HVA. Riluzole did not affect the increase in DA release induced by MPP+ in vitro. The in vivo efficacy of riluzole on MPP(+)-induced DA release could be due to its central interference with glutamatergic transmission. Our data point to a protective role of riluzole with regard to DA release, a marker of the neuronal impairment induced by MPP+, a pro-parkinsonian neurotoxin. PMID- 7865767 TI - Pharmacological characterization of the cloned kappa opioid receptor as a kappa 1b subtype. AB - Substantial pharmacological evidence in vitro and in vivo has suggested the existence of subtypes of the kappa opioid receptor. Quantitative radioligand binding techniques resolved the presence of two high affinity binding sites for the kappa 1 ligand [3H]U69,593 in mouse brain membranes, termed kappa 1a and kappa 1b, respectively. Whereas the kappa 1a site has high affinity for fedotozine and oxymorphindole and low affinity for bremazocine and alpha neoendorphin, site kappa 1b has high affinity for bremazocine and alpha neoendorphin and low affinity for fedotozine and oxymorphindole. CI-977 and U69,593 bind equally well at both sites. To determine the relationship between these kappa 1 receptor subtypes and the recently cloned mouse kappa 1 receptor (KOR), we examined [3H]U69,593 binding to the KOR in stably transfected cells (KORCHN-8). Competition of [3H]U69,593 binding to the KOR by bremazocine, alpha neoendorphin, fedotozine and oxymorphindole resolved a single class of binding sites at which these agents had binding affinities similar to that of the kappa 1b site present in mouse brain. These results suggest that the cloned KOR corresponds to the kappa 1 site in mouse brain defined as kappa 1b. PMID- 7865768 TI - Tau-mutant hamster SCN clock neurones express a 20 h firing rate rhythm in vitro. AB - In vitro neurophysiological studies have demonstrated a circadian rhythm with a period of 24 h in spontaneous neuronal discharge frequency within the rodent suprachiasmatic nucleus (SCN) circadian clock. This report examines the 'circadian' firing rate rhythm in the SCN of the homozygous Tau-mutant Syrian hamster which expresses a short period behavioural rhythm. The spontaneous SCN neuronal firing rate patterns are similar to those observed in wild types. The Tau SCN firing rate rhythm displays a peak in neuronal activity occurring 5-6 h before the predicted onset of wheel-running activity, with a peak-to-peak period of 20 h. This period of the rhythm of spontaneous neuronal discharge within the Tau-mutant SCN parallels the behavioural free-running period of 20 h. PMID- 7865769 TI - Intracerebral microinjections of dermorphin: search for the epileptic induction thresholds. AB - To test the different sensitivity of several central structures to the epileptogenic action of mu opiate agonists, intracerebral microinjections of the selective mu agonist dermorphin were delivered into different areas of the rat dorsal and ventral hippocampus, septum, amygdala, entorhinal cortex, thalamus, striatum and neocortex. The dose of dermorphin (up to 6 nmol) necessary to trigger electrical epileptic events in each of these regions was studied. Epileptic discharges were triggered only in the ventral hippocampus (CA1 and CA3 areas), amygdala and entorhinal cortex. The epileptic induction threshold was the lowest in the CA1 area of the ventral hippocampus. The results suggest that when a mu opiate agonist is injected intraventricularly, the epileptic activity originates in the ventral hippocampus. PMID- 7865770 TI - Brain potentials and the availability of semantic and phonological codes over time. AB - ERPs were recorded from subjects performing semantic and rhyme matching tasks using either spoken words, printed words or pictures as stimuli. Mismatches enhanced N400 (in the semantic task) and N450 (in the rhyme task). Onset and peak latencies were shorter for N450 than for N400 with spoken words; this relationship was inverted for pictures. Thus these latencies could index availability of semantic and phonological codes. For printed words, the latencies were shorter for N400 than N450, a result that supports direct-access modes of reading with late phonological code activation. The longer latencies found for N400 and N450 to pictures could suggest longer initial decoding for pictures with respect to words. PMID- 7865771 TI - c-fos antisense attenuates Fos expression in rat central neurons induced by hemorrhage. AB - Hemorrhage caused by withdrawing 3-4 cm3 of blood from adult rats over a period of 1-2 h induced the expression of Fos proteins, which were detected by immunocytochemical methods in neurons of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, area postrema, nucleus of the solitary tract (NTS), ventrolateral medulla (VLM) and in intermediolateral cell column (IML) of the spinal cord. Daily intraventricular (i.c.v.) injections of c-fos antisense (50 nmol 5 microliters -1) for 2 days prior to hemorrhage markedly attenuated the extent and intensity of Fos-immunoreactivity (FOS-IR) compared with that of rats injected with c-fos sense in the areas mentioned above. The results indicate the effectiveness of i.c.v. administration of c-fos antisense in blocking Fos expression in central neurons following hemorrhage. PMID- 7865772 TI - Corticotropin-releasing hormone (CRH) antisense oligodeoxynucleotide induces anxiolytic effects in rat. AB - Antisense oligodeoxynucleotide complementary to the start coding region of rat corticotropin releasing hormone (CRH) mRNA was intracerebroventricularly infused into rats three times at 12-h intervals. In the shuttle-box avoidance procedure antisense-treated rats showed, within 6 h, significant acceleration and increase in the total number of discriminative avoidance responses compared with controls, treated with the corresponding sense probe or vehicle alone. Following the shuttle-box experiment hypothalamic CRH hybridization signals and immunoreactivity were reduced, while CRH immunoreactivity in the median eminence remained unchanged. Plasma ACTH and corticosterone were decreased in antisense treated animals. It is likely that in addition to a selective blockade of CRH translation, antisense treatment may also interrupt secretion of CRH. Antisense targeting of the hypothalamo-hypophysial-adrenal axis may provide new strategies for the neuropharmacology of affective disorders. PMID- 7865773 TI - Intergeniculate leaflet ablation alters circadian rhythms in the mouse. AB - The intergeniculate leaflet (IGL) receives retinal input and sends afferents to the hypothalamic suprachiasmatic nucleus (SCN), a circadian oscillator. The effect of IGL ablation on the circadian rhythm of wheel-running activity was examined in mice maintained in constant dark (DD) and in two intensities of constant light (LL). IGL-lesioned animals demonstrated significantly longer free running rhythms in DD conditions than IGL-intact mice similarly housed; there was no effect of IGL ablation on the period of the free-running activity rhythm in LL of either 10 or 100 lux intensity. A change in the period of the free-running activity rhythm in DD following IGL destruction is evidence that the IGL exerts an endogenous influence on the SCN circadian system. PMID- 7865774 TI - Non-spatial learning following posterior parietal or hippocampal lesions. AB - Posterior parietal, hippocampal, or sham-lesioned rats were tested for the acquisition of a non-monotonic serial learning task. The performance of control rats and those with a posterior parietal lesion was similar, while those with hippocampal damage demonstrated a working memory deficit. The results are integrated with contemporary conceptualizations of hippocampal and posterior parietal cortex involvement in learning and memory for non-spatial tasks. PMID- 7865775 TI - The role of the left prefrontal cortex in verbal processing: semantic processing or willed action? AB - This study was designed to test the various proposed explanations (semantic processing, willed action, production of a spoken response) for the unilateral activation of the left prefrontal cortex noted in PET studies of verbal processing. Twenty subjects underwent 15O-water PET scans while undertaking a lexical task (detecting the letter 'a' in visually presented words) and a semantic task (categorizing nouns into living/non-living). The semantic task resulted in a significant unilateral left dorsolateral prefrontal activation. This finding suggests that the left inferior prefrontal cortex is the anatomical region involved in 'working with meaning', and that the activation does not reflect willed action, is not task-specific and is not attributable to the requirements of a spoken response. PMID- 7865776 TI - Immunocharacterization of H-2Kb-tsA58 transgenic mouse hippocampal neuroepithelial cells. AB - From dissected fragments of embryonic H-2Kb-tsA58 transgenic mouse hippocampal neuroepithelium, we have derived a population of rapidly proliferating, nestin positive conditionally immortal hippocampal neuroepithelial cells. Treatment with dibutyryl cAMP in non-permissive culture conditions resulted in cessation of cell division and differentiation of the precursor cells into neuronal or glial phenotypes. PMID- 7865777 TI - Protein synthesis inhibitor phase shifts vasopressin rhythms in long-term suprachiasmatic cultures. AB - The effects of anisomycin, a protein synthesis inhibitor, on the circadian rhythm of arginine-vasopressin (AVP) release in organotypic slice cultures of the rat suprachiasmatic nucleus were examined. Anisomycin applied to the culture as a 6-h pulse shifted the phase of the AVP rhythm, depending on the circadian phase at which the pulse was given. The resultant phase-response curve consisted of a delay portion throughout the late subjective night and an advance portion in the middle of subjective day. The present findings suggest that protein synthesis is an important process which constitutes the circadian oscillation and/or the input pathway to the circadian pacemaker within the suprachiasmatic nucleus. PMID- 7865778 TI - Nitroprusside inhibits neurotransmitter release at the frog neuromuscular junction. AB - Sodium nitroprusside (SNP), when applied at concentrations ranging from 0.01 microM to 1.0 mM, reduced endplate potentials in sartorius muscle fibers of the frog (Rana pipiens) by a mean of 57% (range 37-79%). Using quantal analysis, this reduction was shown to be predominantly, if not exclusively, due to a reduction in neurotransmitter release rather than a decrease in postsynaptic sensitivity. Inhibition of neuromuscular transmission was not observed if the preparation was pretreated with bovine hemoglobin prior to the addition SNP nor if 'old' SNP solutions, in which the SNP had decomposed for at least 24 h, were applied. These results suggest that nitric oxide inhibits the evoked release of neurotransmitter at the frog neuromuscular junction. PMID- 7865779 TI - Identification of several soybean cytosolic glutamine synthetase transcripts highly or specifically expressed in nodules: expression studies using one of the corresponding genes in transgenic Lotus corniculatus. AB - A DNA fragment containing sequences hybridizing to the 5' region of GS15, a gene encoding soybean cytosolic glutamine synthetase, was isolated from a soybean genomic library. Mapping and partial sequence analysis of the genomic clone revealed that it encodes a cytosolic GS gene, GS21, which is different from GS15. In parallel, a number of cDNA clones encoding cytosolic GS were isolated using the coding region of pGS20 as a probe (pGS20 is a cDNA clone which corresponds to a transcript of the GS15 gene). Two new full-length cDNAs designated pGS34 and pGS38 were isolated and sequenced. In the 5' non-coding region a strong homology was found between the two clones and the GS21 gene. However, none of these sequences were identical, which suggests that there are at least three members in this group of genes. In order to determine their relative levels of transcription, specific sequences from pGS34, pGS38 and GS21 were used in an RNAse protection assay. This experiment clearly showed that GS21 and the gene encoding pGS38 are specifically expressed in young or mature nodules, whereas the gene encoding pGS34 is highly transcribed in nodules and constitutively expressed at a lower level in other soybean organs. In order to further analyse the molecular mechanisms controlling GS21 transcription, different fragments of the promoter region were fused to the Escherichia coli reporter gene encoding beta glucuronidase (GUS) and the constructs were introduced into Lotus corniculatus via Agrobacterium rhizogenes-mediated transformation. Analysis of GUS activity showed that the GS21 promoter-GUS constructs were expressed in the vasculature of all vegetative organs. This result is discussed in relation to species-specific metabolic and developmental characteristics of soybean and Lotus. PMID- 7865780 TI - PCR-generated cDNA library of transition-stage maize embryos: cloning and expression of calmodulin genes during early embryogenesis. AB - One hundred maize zygotic embryos microdissected at the transition stage were used to construct a cDNA library after non-selective PCR (NS-PCR) amplification of whole cDNA populations. The library contains 2.3 x 10(5) recombinants and two different calmodulin cDNAs were cloned using a heterologous probe from petunia. Calmodulin expression was confirmed throughout maize embryogenesis at the mRNA, amplified cDNA and protein levels. Sequence analysis suggests a maize origin for both clones and negligible nucleotide changes linked to PCR. This library is the first described for early plant embryos and represents a breakthrough to isolate genes involved in embryo differentiation. PMID- 7865781 TI - Expression of ferredoxin-dependent glutamate synthase in dark-grown pine seedlings. AB - Pine seedlings are able to accumulate chlorophylls and develop green plastids in a light-independent manner. In this work, we have characterized ferredoxin dependent glutamate synthase (EC 1.4.7.1; Fd-GOGAT), a key enzyme in nitrogen interconversion during this process. Fd-GOGAT has been purified about 170-fold from cotyledons of maritime pine (Pinus pinaster). As occurs in angiosperms, the native enzyme is a single polypeptide with an apparent molecular mass of 163-168 kDa that is confined to the chloroplast stroma. Polyclonal antibodies generated against the purified enzyme were used to immunoscreen a lambda gt11 expression library from Scots pine (Pinus sylvestris) seedlings and partial cDNA clones were isolated and characterized. The clone with the longest cDNA insert (pGOP44) contained the codification for the C-terminal (550 amino acids) of the pine Fd GOGAT polypeptide. Immunological cross-reactivity and comparative amino sequence analysis revealed that Fd-GOGAT is a well conserved protein in higher plants. Western blot analyses showed that protein was expressed in chloroplast-containing pine tissues and this expression pattern was not affected by exogenously supplied nitrogen. Fd-GOGAT mRNA, polypeptide and enzyme activity accumulated in substantial amounts in dark-grown pine seedlings. The presence of a functional Fd GOGAT may be important to provide the required glutamate for the biosynthesis of nitrogen compounds during chloroplast biogenesis in the dark. PMID- 7865782 TI - A chimeric Lhcb::Nia gene: an inducible counter selection system for mutants in the phytochrome signal transduction pathway. AB - One approach towards understanding the transduction pathways of phytochromes is the selection of mutants impaired in various steps. We report here the construction of an inducible counter-selection system for such mutants employing the enzyme nitrate reductase. This enzyme can convert the benign substrate analogue chlorate to the toxic product chlorite, resulting in severe growth inhibition. An Arabidopsis thaliana nitrate reductase gene (Nial*2) was placed under the regulation of an Arabidopsis thaliana light-harvesting chlorophyll a/b protein (Lhcb1*3) promoter that is phytochrome-responsive. The chimeric Lhcb::Nia gene was transformed into A. thaliana. Homozygous transformant lines were selected and grown in the absence of nitrate and the presence of L-glutamine, conditions that substantially inhibited the expression of the endogenous nitrate reductase genes. In darkness seedlings of the transformed lines were resistant to chlorate; however, when seedlings were grown with intermittent red light, increased sensitivity to chlorate was observed. This sensitivity was correlated with an increase in both Nia1*2 RNA levels and nitrate reductase activity. The resistant seedlings were clearly distinguishable from the sensitive ones based on hypocotyl length, with no overlap in this parameter between the two populations. Thus, this system should allow for the selection of mutants that are impaired in phytochrome regulation of the transcription of Lhcb genes. PMID- 7865784 TI - Diurnal Lhc gene expression is present in many but not all species of the plant kingdom. AB - The diurnal and circadian expression of light-harvesting genes (Lhc) is well documented for many plant species of the 'Angiospermae' division. Here we present the diurnal mRNA levels of species of the Gymnospermae, Pteridophyta, Bryophyta and Phycophyta divisions. Except for four Coniferophytina species, diurnal Lhc mRNA accumulation is detected in fern, moss and algae, supporting the idea that the concept of 'ciracadian clock'-controlled gene expression is an ancient process. Possible reasons why plants need the 'circadian clock' control mechanism are discussed. PMID- 7865783 TI - Molecular cloning and characterization of profilin from tobacco (Nicotiana tabacum): increased profilin expression during pollen maturation. AB - Profilin has recently been identified as an actin-binding protein in higher plants. A cDNA coding for tobacco profilin, which shared an average sequence identity of 75% with other plant profilins, was isolated from a tobacco pollen cDNA library by antibody screening. Tobacco profilin was expressed in Escherichia coli and purified by affinity to poly-(L-proline) Sepharose. A rabbit antiserum was raised against recombinant tobacco profilin and used to estimate the amount of profilin expressed in different tobacco tissues. Profilin can be detected in different somatic tissues, but the expression is 50-100 fold higher in mature pollen. Immunofluorescence and confocal laser scanning microscopy showed a homogeneous distribution of profilin in the cytoplasm of in vitro cultured pollen grains and pollen tubes of tobacco whereas some growing pollen tubes were stained more intensively a their tip. A possible role of pollen profilin as a developmentally upregulated microfilament precursor in mature pollen is discussed. PMID- 7865785 TI - Isolation and characterization of homeobox-containing genes of carrot. AB - Homeodomains (HDs) are DNA-binding domains that have been well characterized in animals, and HD proteins are thought to be regulators of transcription. To investigate the regulation of gene expression during somatic embryogenesis in carrot, an attempt was made to isolate cDNA clones that encode HD proteins. A cDNA library from carrot somatic embryos was screened with a degenerate oligonucleotide probe that corresponded to a conserved amino acid sequence of HDs, and one cDNA clone (CHB1) encoding an HD protein was isolated. The amino acid sequence deduced from the nucleotide sequence of this clone contained a putative leucine zipper motif adjacent to the anticipated HD. The homeodomain/leucine zipper (HD-Zip) sequence of this cDNA was used for further screening, and five additional independent clones (CHB2 through CHB6) were isolated. Although the HD-Zip sequences encoded by these clones were similar to each other, the sequences beyond the HD-Zip regions varied greatly. Transcripts corresponding to CHB1 through CHB6 were expressed at different times during somatic embryogenesis. In particular, transcripts corresponding to CHB2 were expressed in close association with the early development of embryos. PMID- 7865786 TI - Structure and expression of a nitrite reductase gene from bean (Phaseolus vulgaris) and promoter analysis in transgenic tobacco. AB - A structural gene encoding nitrite reductase (NiR) in bean (Phaseolus vulgaris) has been cloned and sequenced. The NiR gene is present as a single copy encoding a protein of 582 amino acids. The bean NiR protein is synthesized as a precursor with an amino-terminal transit peptide (TP) consisting of 18 amino acid residues. The bean NiR transit peptide shows similarity to the TPs of other known plant NiRs. The NiR gene is expressed in trifoliate leaves and in roots of 20-day old bean plants where transcript accumulation is nitrate-inducible. Gene expression occurs in a circadian rhythm and induced by light in leaves of dark-adapted plants. A particular 100 bp sequence is present in the promoter and in the first intron of the NiR gene. Several copies of this 100 bp sequence are present in the bean genome. Comparisons between the promoter of the bean NiR gene and of two bean nitrate reductase genes (NR1 and NR2) show a limited number of conserved motifs, although the genes are presumed to be co-regulated. Comparisons are also made between the bean NiR promoter and the spinach NiR promoter. Transformation of tobacco plants with the bean NiR promoter fused to the GUS reporter gene (beta glucuronidase) shows that the bean NiR promoter is nitrate-regulated and that the presence of the 100 bp sequence influences the level of GUS activity. NiR-coding sequences are not required for nitrate regulation but have a quantitative effect on the measured GUS activity. PMID- 7865787 TI - A type I element composed of the hexamer (ACGTCA) and octamer (CGCGGATC) motifs plays a role(s) in meristematic expression of a wheat histone H3 gene in transgenic rice plants. AB - Type I element (CCACGTCACCGATCCGCG) is a well-conserved regulatory element found in proximal promoter region of a certain class of plant histone genes, that is composed of two independent cis-acting elements of the hexamer (ACGTCA) and the reverse-oriented octamer (GATCCGCG) motifs. To investigate functional role(s) of the type I element in regulation of a wheat histone H3 gene (TH012) promoter activity in vivo, base substitution mutations were introduced into the element and activities of the mutated promoters were examined in cultured rice cells, and in regenerated roots and anther walls of transgenic rice plants by employing a GUS reporter system. Mutations of each or both of the hexamer and the octamer motifs caused a reduction in the promoter activity in protoplasts transfected transiently or stably transformed calli. The mutation of the octamer motif with or without the mutation of the hexamer motif caused a marked reduction of the promoter activity in the root meristem of transgenic rice although the mutation of the hexamer motif alone caused a weak reduction. In contrast to these results, no effect of the mutations of either the hexamer or the octamer motif was found in the anther wall in which replication-independent activity of the H3 promoter was observed. Our results suggested that the hexamer and the octamer motifs may play important role(s) in regulation of replication-dependent but not of replication-independent expression of the wheat histone H3 gene. PMID- 7865788 TI - Characterization of plastocyanin from the cyanobacterium Phormidium laminosum: copper-inducible expression and SecA-dependent targeting in Escherichia coli. AB - Plastocyanin from the thermophilic cyanobacterium Phormidium laminosum has been purified, a partial amino acid sequence obtained and the gene cloned and sequenced. The derived amino acid sequence indicates that the plastocyanin protein is initially synthesized with an N-terminal leader sequence of 34 amino acids to direct it across the thylakoid membrane. The leader sequence consists of a positively charged N-terminal region, a hydrophobic region and a cleavage site, which are characteristic both of higher-plant chloroplast thylakoid transfer domains and of bacterial leader peptides. The petE gene and flanking regions have been cloned in Escherichia coli, and the plastocyanin protein is expressed and directed to the periplasmic space, with concomitant processing to the mature form. Targeting to the periplasm and processing of the plastocyanin protein in E. coli appears to be dependent on components of the Sec apparatus, since the unprocessed precursor accumulates in the cytoplasm of a secA mutant. Expression of plastocyanin in E. coli is copper-inducible and apparently controlled at the level of transcription, leading to the conclusion that copper-regulated promoters exist in the regions flanking the gene and are recognized in a heterologous system. Possible implications for gene expression and protein targeting in the cyanobacterium are discussed. PMID- 7865789 TI - Isolation and expression analysis of cDNA clones encoding a small and a large subunit of ADP-glucose pyrophosphorylase from sugar beet. AB - The cDNA cloning of a small and a large subunit of ADP-glucose pyrophosphorylase (AGPase) from sugar beet is reported. The deduced amino acid sequences are highly homologous to previously identified AGPase polypeptides from other plant species. Both subunits are encoded by low copy genes. When RNA gel blot experiments were performed, strongest expression was detected in sink and source leaves of greenhouse-grown sugar beet plants. A lower expression was found in other tissues tested, i.e. in the hypocotyl, the tap root and roots. In these tissues, slightly higher transcript levels were found for the small subunit gene than for the large subunit gene. PMID- 7865790 TI - Cloning and sequence analysis of a signal peptidase I from the thermophilic cyanobacterium Phormidium laminosum. AB - Type I signal peptidases are a widespread family of enzymes which remove the presequences from proteins translocated across cell membranes, including thylakoid and cytoplasmic membranes of cyanobacteria and thylakoid membranes of chloroplasts. We have cloned and sequenced a signal peptidase gene from the thermophilic cyanobacterium Phormidium laminosum which is believed to encode an enzyme common to both membrane systems. The deduced amino acid sequence is 203 residues long and although the overall similarity among signal peptidases is rather low there are a number of identifiable conserved regions present. The P. laminosum enzyme is predicted to have a single transmembrane domain, in contrast to other Gram-negative bacterial sequences, but similar to other type I signal peptidases. PMID- 7865791 TI - Molecular characterization of cDNAs corresponding to genes expressed during almond (Prunus amygdalus Batsch) seed development. AB - A number of different cDNA clones corresponding to the most abundant mRNAs present in immature seeds have been isolated from an almond (Prunus amygdalus cv. Texas) immature seed cDNA library. Those corresponding to proteins involved in storage processes have been further characterized. Two of these cDNAs (PA3BF1 and PA3BE12) code for the almond globulins (prunins), the main family of storage proteins synthesized in seeds during embryogenesis, and another cDNA (PA3BA1) codes for the 15.7 kDa almond oleosin, a protein located on the surface of oil bodies in plant seeds. These cDNAs have been sequenced and their expression during almond fruit development has been studied. Their expression is seed specific and localized in cotyledons around 100 days after flowering. Both prunin and oleosin genes are present in one or two copies in the almond genome. PMID- 7865792 TI - A proline-rich chitinase from Beta vulgaris. AB - A gene (Ch1) encoding a novel type of chitinase was isolated from Beta vulgaris. The Ch1 protein consists of an N-terminal hydrophobic prepeptide of 25 amino acids followed by a hevein-like domain of 22 amino acid residues, an unusually long proline-rich domain of 131 amino acid residues with 90 prolines, and finally a catalytic domain of 261 amino acid residues. Proteins with similar proline-rich domains are present in some other plants. The Ch1 gene shows a transient expression in response to fungal infection. PMID- 7865793 TI - Inflorescence-specific expression of AtK-1, a novel Arabidopsis thaliana homologue of shaggy/glycogen synthase kinase-3. AB - We report here the isolation of the Arabidopsis thaliana gene AtK-1. The predicted protein sequence of AtK-1 shows 70% identity to the Arabidopsis ASK and alfalfa MsK kinases that are homologs of the Drosophila shaggy and rat GSK-3 serine/threonine protein kinases playing an important role in signal transduction processes in animals. Northern analysis of different organs revealed exclusive expression in inflorescences suggesting an involvement of the AtK-1 kinase in reproduction-specific processes. PMID- 7865794 TI - Light-regulated expression of the Arabidopsis thaliana ferredoxin gene requires sequences upstream and downstream of the transcription initiation site. AB - The effect of light on the expression of the Arabidopsis thaliana ferredoxin gene (fedA) was studied in mature tobacco plants. In light-treated leaves of tobacco plants transformed with a full-length ferredoxin gene, fedA-specific mRNA levels were more than twenty fold higher than in dark-treated controls. This indicates that all components for regulation of the Arabidopsis ferredoxin gene are present in tobacco. To identify light-regulatory elements in the fedA gene, we have tested a set of chimeric genes containing various parts of the fedA gene for light-dependent expression in mature tobacco plants. A fedA promoter-GUS fusion gene was not light-responsive, indicating that the 5'-upstream promoter region is not sufficient for light regulation. Fusion genes in which different transcribed regions of the fedA gene were expressed from the CaMV 35S promoter showed only limited light regulation, if any at all. This indicates that, like the fedA upstream region, the region downstream of the transcription start site is also not sufficient for full light regulation. The combined results suggest that for full light-regulated expression of the fedA gene, both the promoter region and sequences downstream of the transcription start site are required. PMID- 7865795 TI - Identification of the Agrobacterium tumefaciens C58 T-DNA genes e and f and their impact on crown gall tumour formation. AB - DNA sequence analysis of the 4.4 kilobases (kb) Eco RI fragment 14 from T-DNA of Agrobacterium tumefaciens C58 revealed three open reading frames. One of them (945 bp) was supposed to encode the transcript e, the function of which has not been identified to date. Furthermore, a so far undescribed open reading frame (1035 bp) was identified, located in the centre of the Eco RI fragment 14 and termed gene f. The third open reading frame encoded the carboxy-terminal part of the agrocinopine synthase (Acs). The gene e-encoded protein showed significant homologies to the gene products of the Agrobacterium rhizogenes rolB gene and the Agrobacterium tumefaciens gene 5. Both gene products are supposed to regulate the plant's reaction on auxin. Depending on the plant species tested, Agrobacterium strains carrying mutations in gene e induced only small or almost no detectable crown gall tumours. According to these mutational studies and the protein homologies observed, the gene e product is suggested to be involved in tumour formation. Infection of several plant species with Agrobacterium carrying a mutated gene f, as well as expression of the gene f in transgenic tobacco plants did not lead to visible morphological changes. Therefore, in contrast to gene e, the gene f seems not to be essential for tumour formation. In order to study whether gene f is an active gene, its expression in agrobacteria and plants was monitored by translational lacZ fusion. In planta, the putative gene f-promoter mediates a tissue-specific expression pattern. Although gene f was expressed in free-living agrobacteria as well as in transgenic plants, the function of the f locus remained unclear. DNA homology studies with the f gene region revealed a mosaic-like DNA structure, indicating that this locus might be the result of genetic exchanges between different Agrobacterium strains during evolution. PMID- 7865796 TI - Rapid changes in oxidative metabolism as a consequence of elicitor treatment of suspension-cultured cells of French bean (Phaseolus vulgaris L.). AB - Stressed plant cells often show increased oxygen uptake which can manifest itself in the transient production of active oxygen species, the oxidative burst. There is a lack of information on the redox status of cells during the early stages of biotic stress. In this paper we measure oxygen uptake and the levels of redox intermediates NAD/NADH and ATP and show the transient induction of the marker enzyme for redox stress, alcohol dehydrogenase. Rapid changes in the redox potential of elicitor-treated suspension cultures of French bean cells indicate that, paradoxically, during the period of maximum oxygen uptake the levels of ATP and the NADH/NAD ratio fall in a way that indicates the occurrence of stress in oxidative metabolism. This period coincides with the maximum production of active oxygen species particularly H2O2. The cells recover and start producing ATP immediately of H2O2 production. This indicates that the increased O2 uptake is primarily incorporated into active O2 species. A second consequence of these changes is probably a transient compromising of the respiratory status of the cells as indicated in expression of alcohol dehydrogenase. Elicitor-induced bean ADH was purified to homogeneity and the M(r) 40,000 polypeptide was subjected to amino acid sequencing. 15% of the whole protein was sequenced from three peptides and was found to have nearly 100% sequence similarity to the amino acid sequence for pea ADH1 (PSADH1). The cDNA coding for the pea enzyme was used to demonstrate the transient induction of ADH mRNA in elicitor-treated bean cells. Enzyme activity levels also increased transiently subsequently. Increased oxygen uptake has previously been thought to be associated with provision of energy for the changes in biosynthesis that occur rapidly after perception of the stress signal. However the present work shows that this rapid increase in oxygen uptake as a consequence of elicitor action is not wholly associated with respiration. PMID- 7865797 TI - Conifer homologues to genes that control floral development in angiosperms. AB - A set of MADS-box genes in flowering plants encode transcription factors that control both flower meristem formation and organ identity in the developing flower. In this report we present the first documentation of the presence of MADS box genes in a non-flowering seed plant, and indeed from a plant bearing truly unisexual reproductive axes. A MADS-box-specific screening of a cDNA library from immature female strobili of the conifer Norway spruce, Picea abies (L.) Karst, resulted in cDNA clones that correspond to three different deficiens-agamous-like (dal) genes, dal1, dal2 and dal3. In addition to the MADS box, the spruce genes contain a second sequence element conserved among angiosperm genes, the K box, which is located downstream to the MADS box. A phylogenetic analysis of the nucleotide sequences confirms common ancestry of the gene superfamily. dal1 is related to agl2, agl4 and agl6 from Arabidopsis thaliana, all genes with unknown functions, and is expressed in vegetative as well as reproductive shoots on the adult spruce tree. dal2 is sister to angiosperm genes that control the identity of sexual organs, and is expressed only in the developing male and female strobili. dal3 is related to the vegetatively expressed tomato gene tm3 and is transcribed in both vegetative and reproductive shoots. These results strongly suggest that the functional and structural complexity within the MADS-box superfamily of reproduction-control genes is an ancestral property of seed plants and not a novelty in the angiosperm lineage. PMID- 7865798 TI - Molecular characterization of plastid pyruvate kinase from castor and tobacco. AB - Clones encoding two different forms of plastid pyruvate kinase (PKp; EC 2.7.1.40) have been isolated from both castor and tobacco seed cDNA libraries. One form, designated PKpA, from castor was described in a previous report, and the tobacco homologue of PKpA has now been isolated. In addition, a second cDNA, designated PKpG, has been identified and sequenced in both species. Western blot analysis, using antibodies raised against protein overexpressed from these clones, indicates that they encode the two predominant polypeptides of plastid pyruvate kinase from developing castor endosperm. In castor, both PKpA and PKpG are encoded by single genes. In the allotetraploid Nicotiana tabacum, there are two copies of each, one derived from each of the progenitors of this species. The expression of the genes for PKpA and PKpG was examined in various tissues from both castor and tobacco. In castor, both forms are expressed in developing and germinating endosperm and in the root but neither is expressed in the leaf. In tobacco, both forms are expressed in developing seeds but in mature tissues, PKpA is most abundant in roots and PKpG in leaves. PMID- 7865799 TI - Inheritance of gusA and neo genes in transgenic rice. AB - Inheritance of foreign genes neo and gusA in rice (Oryza sativa L. cv. IR54 and Radon) has been investigated in three different primary (T0) transformants and their progeny plants. T0 plants were obtained by co-transforming protoplasts from two different rice suspension cultures with the neomycin phosphotransferase II gene [neo or aph (3') II] and the beta-glucuronidase gene (uidA or gusA) residing on separate chimeric plasmid constructs. The suspension cultures were derived from callus of immature embryos of indica variety IR54 and japonica variety Radon. One transgenic line of Radon (AR2) contained neo driven by the CaMV 35S promoter and gusA driven by the rice actin promoter. A second Radon line (R3) contained neo driven by the CaMV 35S promoter and gusA driven by a promoter of the rice tungro bacilliform virus. The third transgenic line, IR54-1, contained neo driven by the CaMV 35S promoter and gusA driven by the CaMV 35S. Inheritance of the transgenes in progeny of the transgenic rice was investigated by Southern blot analysis and enzyme assays. Southern blot analysis of genomic DNA showed that, regardless of copy numbers of the transgenes in the plant genome and the fact that the two transgenes resided on two different plasmids before transformation, the introduced gusA and neo genes were stably transmitted from one generation to another and co-inherited together in transgenic rice progeny plants derived from self-pollination. Analysis of GUS and NPT II activities in T1 to T2 plants provided evidence that inheritance of the gusA and neo genes was in a Mendelian fashion in one plant line (AR2), and in an irregular fashion in the two other plant lines (R3 and IR54-1). Homozygous progeny plants expressing the gusA and neo genes were obtained in the T2 generation of AR2, but the homozygous state was not found in the other two lines of transgenic rice. PMID- 7865800 TI - Regulation of CD40 ligand expression and use of recombinant CD40 ligand for studying B cell growth and differentiation. AB - Helper T cell activation leads to transient expression of a ligand for the B cell surface protein, CD40. CD40 ligand can deliver helper T cell-derived contact signals to B lymphocytes that drive B cell activation and proliferation. Regulation of expression of CD40 ligand is analogous to that of other helper T cell-derived lymphokines. A soluble form of CD40 ligand is capable of delivering proliferative signals to B cells only when cross-linked or when IL-4 is added. Recombinant CD40 ligand in membrane vesicles can be used to develop in vitro systems for studying class switching, clonal selection, and affinity maturation in normal B lymphocytes. PMID- 7865801 TI - T helper cell regulation of normal and neoplastic B cell growth. AB - Following challenge with a thymus-dependent antigen T helper cells regulate B cell growth and differentiation in several ways. Initially, the T cells physically associate with antigen presenting B cells. While in conjugate, the two cells communicate with each other through the actions of cell surface receptors whose ligands are integral membrane proteins expressed on the surface of the apposed cell. The ensuing biochemical pathways regulate the expression of genes required for B cell cycle progression. As a consequence of this interaction, the T cells are induced to synthesize and secrete soluble mediators that also affect B cell proliferation, as well as determining the ultimate fate of the activated B cell. We also suggest a role for normal, Th cells during the development, and continued expansion of certain types of B cell lymphomas. PMID- 7865802 TI - The next wave. PMID- 7865803 TI - Management of suicidal patients with HIV disease. AB - Suicidal acts among people with HIV disease exceed those among the general population. Stress from the HIV diagnosis, treatment, and medications can lead to depression, which increases suicide risk. High quality care of depressed persons depends on sound scientific knowledge of evaluation of suicide. Incidence, epidemiology, risk factors, evaluation, and treatment of suicidal people are the core of this article. A patient's comment, "I'd be better off dead," deserves investigation as a cry for help and a clue to impending suicide. PMID- 7865804 TI - A comparison of calculated energy requirements to measured resting energy expenditure in HIV-1-infected subjects. AB - Twenty HIV-infected outpatients participating in clinical drug trials of the National Institute of Allergy and Infectious Diseases (NIAID) and enrolled in the collaborative National Institute of Nursing Research (NINR) nutrition study underwent indirect calorimetry measurements. Energy requirements for these subjects also were calculated using the Harris Benedict Equation (HBE). In all 20 subjects, the calculated energy requirements underestimated actual resting expenditure as determined by indirect calorimetry. PMID- 7865805 TI - Comorbidities of HIV-1/AIDS in adults. AB - The comorbid diagnoses associated with illness due to human immunodeficiency virus type 1 (HIV-1) are cumulative, multiple, and varied. These diagnoses start with primary infection, then progress to symptomatic illness and finally to AIDS indicator diseases. The author reviews this progression and additional variables such as preexisting health problems, socioeconomic status, health insurance coverage, and educational level. Based on an understanding of the preexisting problems, as well as the HIV-1 trajectory, the author outlines the implications for future nursing education, practice, and research. PMID- 7865806 TI - [Free radical mechanisms in cerebral pathologies]. PMID- 7865807 TI - [Effect of immunization to alcohol dehydrogenase on white rat behavior]. PMID- 7865808 TI - [Comparative analysis of effects of prolonged peripheral and intracerebral administration of angiotensin-II to rats]. PMID- 7865809 TI - [The mechanism of intensifying stomach contractions, occurring during stimulation of the sympathetic trunk]. PMID- 7865810 TI - [Relationship between cerebral circulation and neuronal activity in animals with varying sensitivity to emotional stress as a predictor of severity of cerebral ischemia]. PMID- 7865811 TI - [Features of developing pain syndromes upon the interaction of generators of pathologically enhanced stimulation]. PMID- 7865812 TI - [Status of adrenergic innervation of heart ventricles in experimental massive embolus of the pulmonary arteries]. PMID- 7865813 TI - [Analgesic effects of peptide factors from the rat spinal cord during formation and development of generators of pathologically enhanced stimulation in it]. PMID- 7865814 TI - [Pathomorphological signs of capillary endothelial damage during trauma and replantation of skeletal muscle]. PMID- 7865815 TI - [Lipid peroxidation in the brain of rats with varying resistance to emotional stress]. PMID- 7865817 TI - [The effect of the phenolic antioxidant katavidan on autoxidation of microsomes during exposure to visible light]. PMID- 7865816 TI - [Insulin receptor interactions and metabolic effects of "essential" phospholipids in diabetes mellitus]. PMID- 7865818 TI - [CO2--a natural inhibitor of active oxygen form generation by phagocytes]. PMID- 7865819 TI - [The effect of hyperbaric conditions on human erythrocyte acetylcholinesterase]. PMID- 7865820 TI - [Inhibition of platelet aggregation with monoclonal antibodies to the glycoprotein IIb-IIIa complex]. PMID- 7865821 TI - [Intracellular accumulation of free doxorubicin and doxorubicin encapsulated in nanospheres]. PMID- 7865822 TI - [The effect of nimodipine on blood circulation in the rat middle cerebral and carotid arteries]. PMID- 7865823 TI - [The neurotropic effect of myelopide on rat motor activity--stereotypical movement, locomotion, and grooming]. PMID- 7865824 TI - [The effect of the synthetic regulatory peptide thymohexin on production of various classes of immunoglobulins]. PMID- 7865825 TI - [Interconnection between expression of surface markers and synthesis of immunoglobulin E by peripheral blood mononuclear cells under the effect of recombinant interleukin-4]. PMID- 7865826 TI - [Effect of recombinant interleukin-4 on immunoglobulin synthesis in cultured human peripheral blood mononuclear cells]. PMID- 7865827 TI - [Characteristics of a mucin-like antigen, expressed on tumors of epithelial genesis]. PMID- 7865828 TI - [Molecular genetic approaches to studying HLA systems: new prospects in basic and applied research]. PMID- 7865830 TI - [The phenomenon of bronchial epithelial atrophy: an ultrastructural-metabolic analysis of the bronchial mucosa in chronic bronchitis]. PMID- 7865829 TI - [A plasmid vector for expressing the human insulin gene in nonendocrine cells]. PMID- 7865831 TI - A new approach to gene diagnosis of Duchenne/Becker muscular dystrophy--amplified fragment length polymorphisms. AB - Four (CA)n repeats, located in introns 44, 45, 49 and 50 of the dystrophin gene, were evaluated in Chinese. These loci are highly polymorphic, with polymorphism information contents of 0.872, 0.772, 0.870 and 0.718, respectively. All four loci can be easily amplified and labelled using two duplex PCR reactions with alpha-32P-dCTP and can be detected by denaturing polyacrylamide gel electrophoresis. Using these four loci and the two polymorphic (CA)n repeats located at the 5' and 3' ends of the dystrophin gene, we have developed a new PCR based procedure--Amp-FLP (amplified fragment length polymorphism) linkage analysis for the gene diagnosis of DMD/BMD. This method can detect intragenic recombination rapidly and efficiently and greatly improves the success rate of carrier detection and prenatal diagnosis in non-deletion DMD/BMD families. All of the loci used in this procedure are intragenic. In addition, the loci in introns 44, 45, 49 and 50 are located in the deletion-prone region of the dystrophin gene, making them valuable and useful in the identification of deletion mutations. Here we report one case of deletion detection using these four loci. PMID- 7865832 TI - Expression of the O6-methylguanine-DNA methyltransferase gene in eight human tumor cell lines. AB - O6-methylguanine-DNA methyltransferase (MGMT) gene expression in 6 Mer+ (HeLa S3, SMMC-7721, SGC-7901, B-239, AGZY83-a, and Cc801) and 2 Mer- (SHG-44, and HeLa MR) human tumor cell lines was examined. Southern blot analysis revealed no deletion, amplification, or rearrangement of the MGMT gene in these cell lines. However, approximately 1.0 kb transcripts were detected in the 6 Mer+ cell lines but not in the 2 Mer- cell lines by Northern blot analysis. Furthermore, a rough correlation between MGMT activity and mRNA level in these cell lines was observed. These results suggest that transcriptional regulation of the MGMT gene is the molecular basis of the absence of MGMT activity in Mer- cell lines. PMID- 7865833 TI - The kinetics of cytoplasmic granule secretion in natural killer cytotoxicity. AB - Antiserum against purified cytoplasmic granules from rat LGL tumor cells, and protein A-gold immunoelectron microscopy were used to study the secretory events in lysis of YAC-1 tumor cells by rat LGL tumor cells or by isolated LGL from normal rats. After 30 min incubation of effector and target cells together, gold labeled cytoplasmic granules were often seen concentrated in the area of the LGL adjacent to the bound YAC-1 target. Within 60 min, the granules were observed to move to the cell border near the conjugated site. At this point, the granules were fused with the cell membrane, and subsequently released the gold-labeled contents into the junction between the LGL and the target cell. Gold particles could be seen at the E-T interface, on the LGL surface, or sometimes on the target cell surface. These data provide direct evidence for the hypothesis that under conditions of active cytotoxicity, natural killer cells secrete their cytoplasmic granule contents leading to the deposition of granule material on the target cell surface and the eventual lysis of the cell. PMID- 7865834 TI - Down-regulation of c-myc oncogene during NGF-induced differentiation of neuroblastoma cell lines. AB - There may be a close relationship between myc oncogenes and carcinogenesis of human neuroblastoma. In previous studies, we were able to induce differentiation of certain neuroblastoma cell lines with NGF. In order to study gene regulation during differentiation, N-myc and c-myc cDNA probes were hybridized with RNA extracted from different cell lines before and after NGF treatment. It was found that cell lines which expressed N-myc did not express c-myc while those with c myc did not express N-myc except for SHEP cell line which had neither c-myc nor N myc expression. In NGF-induced differentiated neuroblastoma cells, c-myc oncogene was down-regulated in comparison with the control samples. The time course of c myc down-regulation was concomitant with the appearance of morphological differentiation. In situ hybridization also showed remarkable reduction of c-myc oncogene expression in NGF-induced differentiated cells as compared with the untreated control cells. These results indicate that down-regulation of c-myc oncogene may be a key event during NGF-induced differentiation and over expression of c-myc oncogene may, at least partially, be responsible for the genesis of neuroblastoma. PMID- 7865835 TI - Ultrastructural study of the hemopoietic microenvironment in human fetal spleen. AB - Reciprocal interactions between hemopoietic stromal cells and immature hemopoietic cells in human spleens obtained from 20 fetuses of 10-28 weeks gestation were observed by transmission electron microscopy and scanning electron microscopy. The close association of stromal cells with immature hemopoietic cells was confirmed under the electron microscope and a presumptive HIM (Hemopoietic inductive microenvironment) was visualized. In regions of immature hemopoietic cell-reticular cell, endothelial cell, macrophage and interdigitating cell contact, some communicating structures were found between the plasma membranes of adjacent cells; moreover, the cytoplasm of these four stromal cells were full of various kinds of organelles. These results suggest that reticular cells, endothelial cells, macrophages and interdigitating cells are component parts of the HIM of human fetal spleen and that these cells have a nurturing function in relation to hemopoietic cells. PMID- 7865836 TI - Experimental study on ischemia and reperfusion injury of rat liver and effects of ligustrazine and salvia compound. AB - The present study was to investigate changes of free radicals in the whole rat liver, changes of ATP levels of hepatic cells, ultrastructural changes in hepatic tissue during ischemia and reperfusion in rats and the effects of ligustrazine and salvia compound. The results indicated that: 1) the free radical levels increased by 8.3-fold and 9.0-fold in the groups with 30 and 60 min ischemia after 40 min reperfusion, as compared with the group with ischemia only (P < 0.01, P < 0.01, respectively). 2) The levels of ATP returned to normal in the group with 30 min ischemia after reperfusion for 40 min and 3 d, remained low in the group with 90 min ischemia and fell again after a mild increase in the group with 60 min ischemia. 3) The hepatic and endothelial cell damage after ischemia became more severe after reperfusion, as revealed by electron microscopy. The present study also showed that ligustrazine and salvia compound have protective effects against reperfusion injury. They can be used to scavenge free radicals, improve hepatic microcirculation and alleviate hepatic and endothelial cell damage. PMID- 7865837 TI - Lipopolysaccharide-induced cytotoxicity against cultured mouse hepatocytes and the role of nonparenchymal liver cells. AB - Lipopolysaccharide (LPS) was found to induce significant hepatocytotoxicity against cultured mouse hepatocytes. Degeneration and necrosis of cultured hepatocytes and decrease of hepatocyte viability were prominent. The aspartate transferase level and 3H-TdR release in the medium were significantly increased after treatment, and the degree of these changes paralleled with LPS concentration. Various other parameters showed no significant difference between the hepatocytes cultured alone and those cocultured with nonparenchymal liver cells. However, if the nonparenchymal liver cells were isolated from mice which had been pretreated with D-galactosamine (GalN) not only was the hepatocytotoxicity induced by LPS enhanced, but the cells also showed certain cytotoxicity against cultured hepatocytes even without LPS. These results suggest that nonparenchymal liver cells might promote LPS-induced hepatocyte injury. PMID- 7865838 TI - 65 cases of preserving pylorus pancreatoduodenectomy: experience and problems. AB - Sixty-five patients with neoplasm (62 cases) or pancreatitis (3 cases) were treated with preserving pylorus pancreatoduodenectomy (PPPD) from 1984 to 1991. One postoperative death occurred. Follow-up studies were performed in 35 patients who had been treated by PPPD or the standard Whipple's procedure; they were questioned carefully concerning clinical symptoms. Further studies were performed in 20 patients with or without pylorus preservation (10 patients, respectively). Nutritional status and gastrointestinal digestive and absorptive functions were evaluated by determination of serum components, gastric analysis, barium emptying time, D-xylose absorption test, 14CO2 breath test, PABA, and other methods. The results demonstrated malnutrition and postgastrectomy syndromes in some patients after the standard Whipple's procedure, but not in those with PPPD. The quality of life was better in the latter. Pylorus preservation may be the main reason for this above difference. Delayed gastric emptying in the early postoperative period was a complication in some patients (21%) treated by PPPD. We recommend PPPD for pancreatoduodenectomy. PMID- 7865839 TI - Signet-ring mucinous adenocarcinoma of the pancreas. AB - An 88-year-old man presented symptoms and signs of ascending cholangitis and died 20 days after the onset of illness. Postmortem examination revealed a mucinous tumor arising from the head of the pancreas, encasing the common bile duct and invading the liver with multiple hepatic metastasis. The tumor showed a unique and uniform histological appearance, consisting of signet-ring neoplastic cells floating in mucin pools. The rapid clinical course and widespread hepatic metastasis of this patient suggest that this pure, signet-ring variant of mucinous adenocarcinoma of the pancreas might have a poorer prognosis. PMID- 7865840 TI - Application of internal fixation in the treatment for tuberculosis of the spine. AB - This is a study of 18 patients who had surgical treatment for spinal tuberculosis. All patients were admitted with the spinal tuberculosis and treated with a combination of anterior debridement and bone graft with posterior internal fixation using the Luque or Dick technique. The patients were able to walk within a few days postoperation. Three to seven years follow-ups show no recurrence, kyphosis and/or solid fusion. PMID- 7865841 TI - Role of collagen metabolism changes in the pathogenesis of pulmonary hypertension in rats and its reversibility. AB - Pulmonary arterial pressure (PAP) was increased obviously in rats after 3 days of normobaric hypoxic exposure and reached a maximum at 14 days of hypoxia. It remained at the same level during prolonged hypoxic exposure of up to 21 days. Right ventricular weight (RV/LV+S) and hydroxyproline (HP) content in the pulmonary artery began to increase at day 7. HP content had increased much faster than the relative rate of increase of PAP after 14 days, but HP content in the thoracic aorta showed no change. The relative proportion of type I to III collagen increased significantly, and compliance of the pulmonary vessels obviously decreased. All parameters returned to the normal range within 14 days after recovery from hypoxia, except for HP content as expressed per vessel. 764-3 treatment obviously attenuated most of the changes caused by hypoxia, though it had no effect on compliance of the pulmonary vessels. It is suggested that collagen, especially type I collagen, accumulation may play an important role in maintaining pulmonary hypertension. 764-3 has certain protective effects and may be useful in the treatment of early chronic obstructive pulmonary disease. PMID- 7865842 TI - Preliminary application of color Doppler flow imaging in the localization of parathyroid adenomas. AB - From December 1991 to April 1993, we performed color Doppler flow imaging (CDFI) in 11 patients with parathyroid adenoma, and all cases were confirmed by operation and pathology. In all the parathyroid adenomas, vessels were clearly revealed at the periphery of the upper pole and/or anterior periphery, where arterial signals were elicited. These arteries had branches into the adenomas and originated from inferior thyroid arteries on the same side in most cases. The internal flow signals were increased markedly as compared to normal thyroid, and high-velocity arterial signals were detected. Because of the thyroid's rich blood supply and landmark peripheral vessels, CDFI can distinguish parathyroid foci from thyroid nodules, lymph nodes, and normal tissues and provide a sound basis for the diagnosis of small parathyroid foci. PMID- 7865843 TI - Clinical assessment of biplanar transesophageal echocardiography--a report of 125 cases. AB - One hundred and twenty-five patients with cardiovascular disease were examined by biplanar transesophageal echocardiography (BTEE), including 67 with rheumatic heart disease (7 monitored during operation), 22 with aortic diseases, 20 with congenital heart diseases, and 16 with other kinds of heart disease. The results showed that BTEE was not influenced by corpulent and pulmonary emphysema and was better than transthoracic echocardiography at imaging the interatrial septum, left atrium and left atrial appendage, thoracic aorta, and mitral artificial valve and at intraoperative monitoring. BTEE was also better than single-plane transesophageal echocardiography, because BTEE could be used to observe the heart and thoracic aorta in transverse and longitudinal planes, thus enlarging the transmission "window" as well as allowing the entire lesion to be imaged. This study suggests that BTEE will have good prospects in clinical application. PMID- 7865844 TI - Abnormal cardiovascular reflexes in patients with achalasia. AB - Using 3 non-invasive tests, abnormalities of cardiovascular reflex function were found in 7 of 15 patients with achalasia. Abnormalities of heart rate responses to the Valsalva maneuver, deep breathing, and standing were noted in patients with autonomic neuropathy defect. The findings are consistent with the hypothesis that an abnormality of vagal function may contribute to the pathogenesis of achalasia. PMID- 7865845 TI - Bone mass, rates of osteoporotic fractures, and prevention of fractures: are there differences between China and Western countries? AB - Fractures are one of the most common causes of disability in older women. The quantity and density of bone decreases with age. Most types of fractures increase as bone density declines. But most of the knowledge about causes and prevention of fractures comes from studies performed in Western countries. Asian women appear to have similar or slightly lower bone density that may be a result of their smaller size. They appear to have a lower risk of hip fracture than Whites, which may be a result of their shorter hip axis. The risks of other types of fractures in Chinese women is less well defined and reasons for differences in the rates of osteoporotic fractures between China and Western countries remain to be explored. A study is underway in Beijing to describe the risks and potential causes of fractures among older women in urban China. Randomized trials in Western countries have demonstrated that calcium and vitamin D, estrogen, calcitonin, or bisphosphonates can reduce the rate of fractures. increased intake of calcium and vitamin D may be the most effective approach to preventing fractures in China, but this should be tested in a randomized trial. PMID- 7865846 TI - Thymidine labeling index and Ki-67 growth fraction in breast cancer: comparison and correlation with prognosis. AB - In situ determination of proliferative activity was performed on 184 consecutive primary invasive breast cancers. Methods used were monoclonal antibody Ki-67 in immunohistochemistry and thymidine labeling index. Tumor proliferation correlated between both methods (p = 0.0001). For thymidine labeling index and Ki-67, respectively, significant correlations existed with histologic tumour grade and steroid hormone receptors (Tumor grade: TLI p = 0.0001; Ki-67 p = 0.0001. ER-ICA: TLI = 0.0001; Ki-67 p = 0.014. PgR-ICA: TLI p = 0.0001; Ki-67 p = 0.0008). For thymidine labeling index a significant correlation was demonstrated for overall survival (p = 0.001) and recurrence free survival (p = 0.01). No statistical significance was observed for clinical outcome and Ki-67 (overall survival p = 0.18; recurrence free survival p = 0.1). None of the factors, TLI or Ki-67, was an independent prognostic factor as demonstrated by multivariate analysis. PMID- 7865847 TI - Constitutive overexpression of the 27,000 dalton heat shock protein in late passage human breast cancer cells. AB - We present evidence that the mechanisms controlling induction of heat shock transcription factors (HSFs) and mRNA expression of the 27,000 molecular weight heat shock protein, hsp27, are diverse in human breast cancer cells. Heat shock accumulation of hsp27 RNA is associated with the activation of HSF in MDA-MB-231 cells. We have later passage MCF-7 breast cancer cell lines with elevated, constitutive expression of hsp27 mRNA, perhaps due to hsp27 gene amplification. Estradiol and heat shock treatment no longer affect the level of hsp27 mRNA in these cells. Heat induction of HSF is inhibited in cells overexpressing hsp27, although metal ions and amino acid analogs are still capable of activating HSF. These cells will provide a useful system for characterizing alternative pathways in HSF inhibition and activation. PMID- 7865848 TI - Establishment and characteristics of two new human mammary carcinoma lines in nude mice with special reference to the estradiol receptor status and the importance of stroma for in vivo and in vitro growth. AB - Two new human mammary carcinoma lines originating from surgical material were established in nude mice. According to the adopted criteria, the tumor 4049 has been classified as estradiol receptor positive and mammary carcinoma 4296 as estradiol receptor negative. Both tumors proved to be c-erbB-2 protein positive and EGF-receptor negative. In contrast to carcinoma 4296, the in vitro growth and the take rate of mammary carcinoma 4049 in nude mice seems to be dependent on stromal components. Pretreatment of mice with estradiol/peanut oil before tumor engraftment was an essential precondition for the growth of the primary tumor in nude mice. After successful establishment the tumor growth was significantly stimulated by estradiol. The growth rate of mammary carcinoma 4296 was independent of any supplementation of estradiol. The two breast tumors were characterized with regard to their growth behaviour, histology, and sensitivity to cytostatics and antihormones. They are considered suitable tumor models for the testing of antineoplastic substances and for biological experiments. PMID- 7865849 TI - Ploidy and S-phase fractions (SPF) of primary breast cancers and their nodal metastases. AB - Ninety-one cases of primary breast cancers and their nodal metastases were examined with DNA flow cytometry. No differences were found between the stemline distributions in the primary tumors and nodal metastases. At both sites stemlines clustered around a DNA index of 1.0 (33-40% of cases) and 1.8. The mean S-phase fractions were 7.9 in primary tumors versus 5.6% in nodal metastases (p = 0.02); this difference was also observed if the analysis was restricted to cases with DNA aneuploidy at both sites (10.2 versus 7.6%, p = 0.04). Our results indicate that axillary nodal ploidy and proliferation reflect primary tumor characteristics rather than displaying changes associated with selection during the lymphatic metastatic process. Lymph nodes may have a suppressive effect on the proliferation of tumor cells. PMID- 7865850 TI - The relationship of urinary and plasma androgens to steroid receptors and menopausal status in breast cancer patients and their influence on survival. AB - The relationships between urinary 11-desoxy-17-oxo steroids (11-DOS), the ratio of 11-DOS to urinary 17-hydroxycorticosteroids (urinary discriminant ratio), plasma levels of the adrenal androgens dehydroepiandrosterone (DHA), DHA sulphate (DHAS), and 7 alpha-hydroxy DHA (7 alpha DHA), and tumour oestrogen receptor (ER) and progesterone receptor (PR) status were examined in pre, peri-, and postmenopausal women with breast cancer. Androgenic steroids and their metabolites decreased with age in women with breast cancer. In perimenopausal women there was a significant association of PR positive tumours and high androgen levels, whereas in postmenopausal women high androgen levels were associated with ER negative tumours. Survival was significantly related to plasma DHA level and tumour steroid receptor status. Thus, adrenal androgen levels below the group mean were associated with significantly decreased survival in women with postmenopausal receptor-positive tumours, and the association was particularly apparent in those who were axillary node negative. Since the number of patients studied was small these results should be regarded as provisional in nature. Nonetheless, the identification of this subgroup of node negative breast cancer women with reduced survival may be important when considering node negative patients for adjuvant therapy. PMID- 7865851 TI - Fine-needle aspiration technique for the concurrent immunocytochemical evaluation of multiple biologic parameters in primary breast carcinoma. AB - Fine-needle aspiration cytology has been already established as a reliable method for the diagnosis of breast cancer. Its application has been recently extended to immunocytochemical analysis of biological parameters. In the current study estrogen and progesterone receptors, Ki67 growth fraction, and p53 protein expression were immunocytochemically evaluated on the cellular material sampled by the same fine-needle aspirate used for the conventional cytologic diagnosis of malignancy. Fine-needle aspiration specimens from 100 patients with primary breast carcinoma were submitted to the immunocytochemical analysis. Twenty-eight percent were in premenopause; 23% had tumors with a diameter less than 2 cm, 59% from 2 to 5 cm, and 18% more than 5 cm; 60% had axillary nodal status negative, 34% positive, and 6% unknown. The concomitant immunocytochemical evaluation of all parameters was possible in 70% of the patients. A significant association was found between p53 overexpression and Ki67 values (p = 0.004), and between Ki67 values and progesterone receptor status (p = 0.003). No correlation was found between any parameter and clinical tumor size. Estrogen (p = 0.02) and progesterone (p = 0.04) receptor negativity and high Ki67 growth fraction (p = 0.005) were significantly associated with the clinical evidence of axillary node involvement. This study suggests that fine-needle aspiration cytology represents an effective practice for a simultaneous evaluation of multiple biologic indicators and could be useful as a preoperative procedure in patients who are candidates for neoadjuvant chemotherapy and/or endocrine therapy. PMID- 7865852 TI - Positive immunostaining for platelet derived growth factor (PDGF) is an adverse prognostic factor in patients with advanced breast cancer. AB - Previous studies suggest a prognostic role for PDGF in patients with breast cancer, with patients with high plasma PDGF levels or positive response to therapy. We have examined a further 58 patients with advanced breast cancer for the presence of tissue PDGF immunostaining. Patients displaying positive tissue immunostaining for PDGF had a highly significant shorter survival (p = 0.002) than patients with no immunostaining. In addition PDGF positive patients treated with combination chemotherapy had a significantly lower response rate (p = 0.05) than PDGF negative patients. These results confirm our previous findings that PDGF may be an important indicator of shortened survival and treatment failure in patients with advanced breast cancer. PMID- 7865854 TI - Breast conservation therapy: local tumor control in patients with pathologically clear margins who receive 5000 cGy breast irradiation without local boost. AB - A retrospective study was performed to determine the value of pathological evaluation of inked primary tumor specimen margins in the local control of patients with stage I and II breast cancer. In 150 patients with 153 invasive breast cancers, treatment involved surgical resection of the primary tumor, pathological determination of tumor-free inked specimen margins, and 5000 cGy whole breast radiation therapy (RT) without tumor bed RT local boost. This approach yielded an actuarial five-year local control rate of 95%. The local control rate was 96% for T-1 cases and 93% for T-2 cases. The local control rate was 96% for patients with clear margins achieved at initial resection and 94% for patients with clear margins achieved at re-excision. Among patients with clear margins at re-excision, the local control rate was 97% for those with no residual cancer and 88% for those with residual cancer. Patients with surgical margins clear by 3 mm or less had a local control rate of 92% at five years. Local control rates appear to be comparable to other breast conservation approaches which routinely employ local RT boosts. In omitting the local RT boost in patients with clear margins, the overall RT course will be briefer and the cosmetic changes associated with high-dose, large volume local RT boosts can be avoided. PMID- 7865853 TI - Are cellular adhesion molecules involved in the metastasis of breast cancer? PMID- 7865855 TI - Antineoplastic activity of alkylphosphocholines (APC) in human breast carcinomas in vivo and in vitro; use of liposomes. AB - This study examines the in vitro and in vivo activity of alkylphosphocholines (APC) in experimental human breast carcinomas. Three analogs, hexadecylphosphocholine (HPC), octadecylphosphocholine (OPC) and eicosanylphosphocholine (EPC) were investigated. Three hormone receptor negative cell lines were sensitive to all three APCs in vitro whereas the receptor positive MCF-7 line was more resistant. Sensitivity was seen in 4/6 hormone receptor negative tumors in vivo, with HPC being the most active analog. There were no antitumor effects in the four receptor positive models. The reasons for these differences in response between hormone receptor negative and -positive lines are not yet understood and require further study. Gastrointestinal toxicity and hemolysis, the major side effects of the APCs, were reduced by the use of liposomal preparations. PMID- 7865856 TI - The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG). AB - In primary, operable breast cancer, the Nottingham Prognostic Index (NPI) based on tumour size, lymph node stage and histological grade can identify three prognostic groups (PGs) with 10-year survival rates of 83%, 52%, and 13%. With the aim of defining a subset of patients having so good prognosis that adjuvant therapy can be withhold, the NPI was applied to a Danish population-based study group comprising 9,149 patients. As opposed to the British study, we used conventional axillary lymph-node staging. Histological grading was in both studies done by means of a similar slight modification of the Bloom and Richardson procedure, but in the Danish study only ductal carcinomas were graded. The 10-year crude survival was 68.1% for 4,791 patients with tumour size < or = 2 cm and 70.0% for 2,900 patients with grade I tumours. For 4,761 node-negative patients, the 10-year survival was also 70.0%, the expected survival being 89.3%. The relative mortality (observed:expected) was even at 10 years 2.1 demonstrating that more than 10 years observation time is necessary to estimate cumulated mortality. By application of the NPI, the Danish good PG comprising 27.3% of the patients had a 10-year survival of 79.0%. Thus, the index defined a subset with better survival than could be defined individually by each of its three components, but it did not succeed in defining a subset with survival similar to the expected; additional prognostic factors are therefore needed. The somewhat poorer survival of the Danish good PG may be ascribed to the British inclusion of non-ductal carcinomas, to interobserver variation present only in the Danish study, and to poorer expected survival of the Danish patients. The 10-year survival of the Danish moderate PG and poor PG was 56% and 25%, respectively. These improved survival rates are attributed to the administration of adjuvant therapies. There were virtually no node-positive patients in the good PG and no node-negative patients in the poor PG. Patients should therefore still be stratified initially by lymph-node status, but tumour size and histological grade are significant prognostic factors primarily within the node-negative group, and they should be included in future prognostication procedures. PMID- 7865857 TI - Relationship of variations in tumor cell kinetics induced by primary chemotherapy to tumor regression and prognosis in locally advanced breast cancer. AB - The relationship of changes in 3H-thymidine labelling index (TLI) induced by primary chemotherapy to tumor response and relapse rate in 36 patients with previously untreated locally advanced breast cancer (LABC) was analyzed. All patients received primary chemotherapy (3 cycles FAC), followed by mastectomy and subsequent adjuvant chemotherapy (3 FAC alternated with 3 CMF). Tumor TLI was evaluated immediately prior to primary chemotherapy and at the time of mastectomy. Median pretreatment TLI was used to discriminate between tumors with a high or low proliferative rate. Clinical objective response to primary chemotherapy was 83% in patients with high TLI and 56% for those with low pretreatment TLI (p = 0.06). Primary chemotherapy induced a > or = 50% reduction of the proliferative rate in 83% and 39% of the tumors with high and low pretreatment TLI, respectively (p = 0.006). Patients were classified into 4 groups according to TLI values both before and after primary chemotherapy: patients who remained in the high TLI group after primary FAC had the highest response rate (100%) and the lowest 2-year relapse rate (20%). These data suggest that: a) improved response to aggressive cytotoxic treatment occurs in tumors with high TLI at diagnosis; b) there is a significant correlation between TLI changes induced by primary chemotherapy and pretreatment proliferative activity; c) patients who remain in the high TLI group after primary chemotherapy are more likely to benefit from subsequent adjuvant systemic therapy. PMID- 7865859 TI - Magnetic resonance imaging detection and wire localization of an 'occult' breast cancer. PMID- 7865860 TI - 17th Annual San Antonio Breast Cancer Symposium. December 6-10, 1994. Abstracts. PMID- 7865858 TI - An alternative approach for treatment of breast cancer. AB - Since adjuvant chemotherapy and hormonal therapy generally extend disease free survival in breast cancer rather than provide a cure, we have examined the current breast cancer paradigm. Heterogeneity is a fundamental characteristic of breast cancer tissue and a well recognized aspect of the disease. There are variations in natural history, histopathology, biochemistry and endocrinology, and molecular biology of cancer tissues and cells within the tissues. A variety of data indicate that growth kinetics are also variable, not only from tumor to tumor, but also during the natural history of an individual's tumor. To better understand kinetic heterogeneity, a stochastic numeric computer model of the natural history of breast cancer has been developed. To be consistent with inter- and intratumor kinetic heterogeneity and with late relapse, the model predicts that tumors grow in an irregular fashion with alternating periods of growth and periods of dormancy rather than the generally accepted modified exponential, or Gompertzian fasion. The prediction of irregular growth has been compared to data relevant to growth characteristics of human breast cancer. Much data support the concept of irregular kinetics and temporary dormancy rather than steady, Gompertzian growth of human breast cancer. Thus, in addition to drug resistance, kinetic heterogeneity may help explain the limited impact that traditional chemotherpeutic treatment has had on mortality from breast cancer. Although the mechanisms underlying irregular growth need to be better understood, non Gompertzian growth kinetics indicates that there may be alternative approaches for breast cancer treatment. PMID- 7865861 TI - Nonparametric scaling: a descriptive index. AB - A descriptive index (CI) based on the U statistic is presented. The CI permits to quantify the differences between experimental samples taking into account both the location and variability features of the data without any distributional assumption. This index can be useful to build activity scales for series of compounds. PMID- 7865862 TI - Emesis induced in domestic pigs: a new experimental tool for detection of antiemetic drugs and for evaluation of emetogenic potential of new anticancer agents. AB - The domestic pig was used to develop a new model for evaluating the emetogenic potential of anticancer drugs and determining the antiemetic activity of drugs. Emesis was characterized by expulsion of solid or liquid material. In each animal, the number of vomits after infusion of the emetogenic drug (infusion in ketamine and xylazine anesthesia) was recorded in 1-hr periods during the first 4 hr and then in a 4- and a 16-hr period. Intravenous infusion of cisplatin caused a concentration-dependent emetic response. Anti-cancer drugs other than cisplatin such as carboplatin, dactinomycin, cyclophosphamide, and ifosfamide, also induced emesis, indicating that the domestic pig is suitable to detect the emetogenic potential of chemotherapeutic agents. A cisplatin dose of 2 mg/kg i.v. proved to be most suitable for studying the effect of potential antiemetic drugs (applied as i.v. injection), because this cisplatin dose caused consistent emetic responses without other toxic signs in the 24 hr following its infusion. Emesis induced by cisplatin was reduced by high doses of metoclopramide (25 mg/pig; approximately 0.8 mg/kg). The more selective dopamine D2 receptor antagonists, alizapride and domperidone, even at high doses (25-50 mg/pig; approximately 0.8 1.6 mg/kg), did not inhibit cisplatin-induced emesis, nor did haloperidol up to 20 mg/pig (approximately 0.6 mg/kg). Sulpride (50 mg/pig; approximately 1.6 mg/kg) halved the occurrence of vomits in the first 4 hr after cisplatin, but this effect was followed by an increase in the frequency of vomits; thus, no change in the total number of vomits was observed in the 24-hr observation period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865863 TI - An evaluation of whether duration of perfusion alters vascular responses in the isolated dual-perfused rabbit liver. AB - The isolated dual-perfused rabbit liver has been used to characterize hepatic arterial vascular receptors. These hepatic arterial responses are reproducible for 2.5 hr. Further studies in relation to the assessment of portal venous responses using this model require longer periods of perfusion. This study was designed to determine if this model is suitable for the assessment of hepatic arterial and portal venous vascular responses over a 5-hr perfusion period. Hepatic arterial responses were consistent to all agents during 5 hr of perfusion. Portal venous responses to the direct smooth muscle acting agents, sodium nitroprusside and adenosine, were constant, but the vasoconstrictor responses to acetylcholine and adenosine 5'-triphosphate (agents that cause an endothelium-independent vasoconstriction and an endothelium-dependent vasodilatation) were potentiated. Coarse measurements of liver function were also performed and suggested that the liver remained viable for the 5 hr of perfusion. These results suggest a decrease in the ability of the endothelium of the portal venous vasculature to respond to vasoactive substances as duration of perfusion increases. The possible reasons for this are discussed. PMID- 7865864 TI - Quantitative evaluation of an experimental inflammation induced with Freund's complete adjuvant in dogs. AB - A chronic inflammation model in dogs was induced by intraarticular injection of Freund's Complete Adjuvant in the stifle. After a primary, acute response during the first 24 hr, a secondary subacute response was observed after a delay of approximately 3 weeks and persisted for several weeks. To evaluate the time course of the inflammatory process quantitatively, we tested more than 100 different parameters. Finally, only four parameters were selected based on practicability and metrological properties, namely, the body temperature, difference in skin temperature, difference in stifle diameter and vertical force exerted by arthritic hind limb measured using a force plate. The main results of the experimentation were the demonstration that these four parameters were sufficiently repeatable, reproducible, and appropriate to be used for quantitative evaluation of the inflammatory process, and that training of both animals and investigators was required. Finally, it was illustrated that an adjuvant periarthritis in dogs can be used to carry out a pharmacokinetic/pharmacodynamic modelling of an antiinflammatory drug. PMID- 7865865 TI - A device for automatic measurement of writhing and its application to the assessment of analgesic agents. AB - A device was developed for automatically measuring writhing in mice so as to be applied to the assessment of analgesic agents. The device was composed of a specially designed container equipped with a detector, namely, a mechanoelectro transducer for writhing. The detector was made up of units of a string, two plates, and two strain gauges. In the unit, each end of the string was connected to either of the plates to which either of the strain gauges was attached. The change in tension of the string due to writhing was converted into the mechanical strain of the plates and then the resistance change of the strain gauges. The resistance change was amplified by a Wheatstone bridge circuit that was connected to a differential amplifier, a high-pass filter, comparator(s), and a monostable multivibrator to obtain the electrical signal for writhing. Using this device, writhing was continuously measured, and evaluation of various types of analgesic agents was performed. The result suggests that this device has sufficient accuracy both for the detection of writhing and the evaluation of analgesics. It has the advantage of automatic measurement of writhing in contrast to the conventional visual observation method. PMID- 7865866 TI - Endothelium-denuded pulmonary resistance arteries from the fetal lamb: preparation and response to vasoactive agents. AB - A method was developed for preparing endothelium-denuded resistance arteries (mean internal diameter, 176 microns) from the term fetal lung to be used for tests in vitro. The endothelium was removed mechanically by passing a sandpaper polished cat whisker through the lumen. Ultrastructurally, the preparation had a well-preserved internal elastic lamina which was facing the lumen without any endothelium superimposed. Its response to contractile agents (excess potassium, a thromboxane A2 analogue, endothelin-1) tended to be greater compared to the intact artery. Conversely, the relaxation to acetylcholine was abolished in the endothelium-denuded artery and, in its place, a modest contraction ensued. Sodium nitroprusside relaxation, unlike acetylcholine relaxation, was affected insignificantly by endothelium denudation. This preparation, in combination with the preparation of the intact resistance artery, is a useful, new tool for studying local factors responsible for pulmonary hemodynamic control in utero and through the transitional period at birth. PMID- 7865867 TI - A nonequilibrium radioimmunoassay for angiotensin II. AB - A method for the measurement of angiotensin II levels in dog plasma is described. The method is similar to previously published assays in that in couples gradient high-performance liquid chromatography (HPLC) with radioimmunoassay (RIA) and requires blood sample collection and processing to plasma in the presence of protease inhibitors. The unique feature of the present method is that it utilized a commercially available angiotensin II RIA run under nonequilibrium conditions. Performing the angiotensin II RIA under nonequilibrium conditions increased RIA sensitivity to allow for a minimal detectable limit of 0.75 pg/mL, a limit of detection not achievable with current commercially available RIAs. This lower limit of detection will now allow for the measurement of circulating levels of angiotensin II. Quality control pools of dog plasma fortified with 4.59-50 pg/mL angiotensin II were assayed and analytical recoveries (ARs) and coefficients of variation (CV) of 72.2%-111% and 3.67%-19.0% were observed for the respective pools. PMID- 7865868 TI - The effects of melatonin in human platelets. AB - Pineal melatonin has been implicated in the control of several physiological processes, including circadian rhythmicity and the photoperiodic control of seasonal breeding in mammals. However, its role in humans remains largely undefined. Presumably, melatonin acts on the CNS to affect biologic rhythms; additionally, a number of studies indicate the existence of direct effects of melatonin in peripheral organs, like the platelets. This article discusses experimental data indicating that the human platelets are peripheral cells sensitive to melatonin that could be potentially employed in clinic studies. Melatonin inhibits several physiological processes in platelets including the aggregation phenomenon the release of ATP and serotonin (indexes of the platelet secretory mechanism), and the production of thromboxane B2 A generally greater, and dose-dependent, effect of nanomolar melatonin concentrations in the evening as compared to morning melatonin found in vivo. The maximum in melatonin activity on platelet function precedes the peak in melatonin concentration in blood, indicating the existence of a dissociation between circulating levels and sensitivity to platelet the hormone in normal subjects. In binding studies employing 3H-melatonin as ligand, binding sites in human platelet membranes with a Kd within the nanomolar range were detected. The data suggest the feasibility to employ platelets as peripheral "windows" of central melatonin activity in humans. PMID- 7865869 TI - Water and ion coupling in the rat cecum during dietary potassium loading. AB - The transepithelial net water movement (Jw) was minute by minute recorded in the cecum of Wistar rats adapted to a high potassium diet (HKD). The potential difference (PD), short circuit current (SCC) and unidirectional 22Na, 36Cl, and 89Rb fluxes were also measured. The hydrostatic and osmotic permeabilities were not modified by potassium adaptation when a standard bicarbonate buffer was employed. Potassium adaptation implicated the development of a secretory, transport-associated Jw (Jwt), associated to an increase in transepithelial PD, SCC and net sodium transport. Contrary to the case of control rats, no net chloride transport was observed in HKD rats. The secretory Jwt compensated, in the presence of sodium, chloride and bicarbonate, an absorptive Jwt. Water secretion was coupled to net potassium secretion. Replacement of chloride by sulphate ions was paralleled by the development of a net absorptive Jw and by increases in the transepithelial Pd and hydrostatic permeability. Replacement of the bicarbonate buffer by a tris-hepes buffer made drop both the observed absorptive Jw and PD amiloride sensitive Na+ entry was observed. PMID- 7865870 TI - The involvement of taurine in the action mechanism of sodium valproate (VPA) in the treatment of epilepsy. AB - Several lines of evidence have shown that sodium valproate (VPA) mechanism of action in the therapy of epilepsy is based on the phenomena of its interaction with neurotransmitters (GABA), receptor sites and ion channels (1). However, there is no conclusive evidence to show the extent of VPA interactions with other neurotransmitters in the brain. Based on this fact, taurine (an amino acid 'neurotransmitter') found distributed in the brain the visual system may probably be involved in the drug action mechanism of VPA. The application of taurine in experimental and human epilepsy started over thirty years ago (2,3) and it has been known to possess some mild anticonvulsant activity in both humans and experimental animal models (4). This review, therefore, will attempt to draw together all the available information on the involvement of taurine in epilepsy and its possible association with the action mechanism of VPA in suppressing epileptic seizures. Structural and physiological distribution of taurine in the brain will be discussed. Its association with the phenomena of VPA action in epilepsy will be cited. Its neurotransmitter candidacy, involvement in ocular pathology, receptor sites and modulatory activity will be dealt with in relation to valproate action in the therapy of epilepsy. PMID- 7865871 TI - Fatty acid composition and dynamics of phospholipids from fresh water fish Prochilodus lineatus brain and spinal cord. AB - The phospholipid and fatty acid composition of the brain and spinal cord lipids of fresh water fish Prochilodus lineatus ("sabalo") were studied. The fluorescence anisotropy of phospholipids labelled with 1.6-diphenyl 1.3.5 hexatriene, was also investigated. Phosphatidyl-choline was the most abundant phospholipid followed by phosphatidyl-ethanolamine, phosphatidyl-serine, phosphatidyl-inositol and sphingomyelin. The fatty acid composition of all phospholipids except sphingomyelin showed the presence of n-9, n-6 and n-3 series of unsaturated acids. The presence of n-6 polyunsaturated fatty acid was represented by arachidonic acid that was found preferentially in phosphatidyl inositol. N-3 fatty acids were represented by 20:5n-3, 22:5n-3 and 22:6n-3. Docosa 4,7,10,13,16,19 hexaenoic acid was the most abundant of n-3 fatty acids and was preferentially found in phosphatidyl ethanolamine and phosphatidyl serine. The percentage of 22:6n-3 acid decreased with age. The simultaneous presence of n-6 fatty acids (arachidonic acid) and n-3 fatty acids in fresh water fishes contrast with the absence of n-6 fatty acids in nervous tissue of marine fishes. Phosphatidyl choline was the most fluid of all phospholipids from brain and spinal cord. PMID- 7865872 TI - Effect of progesterone on the hypothalamic cAMP concentration in estradiol-primed rats. AB - The effect of progesterone on the concentration of adenosine 3',5' cyclic monophosphate (cAMP) in the hypothalamus of ovariectomized estradiol primed rats was studied. Progesterone (2 mg/rat), injected 3 days after the priming dose of estradiol benzoate into ovariectomized rats, produced 4 h later an increase in the hypothalamic nucleotide content; whereas the lowest levels of cAMP were found 24 h after progesterone injection suggesting a biphasic response. The increase of hypothalamic cAMP observed at 4h of progesterone injection was blocked by the administration of an alpha(phenoxybenzamine) or a beta-adrenoblocker (propranolol) suggesting the participation of both, alpha and beta adrenergic receptors. Nevertheless, the administration of diethyldithiocarbamate, a blocker of norepinephrine synthesis has no effect to prevent the increase of hypothalamic cAMP induced by progesterone. Since no changes were observed in the hypothalamic cAMP concentration in the animals killed by afternoon, it may be inferred that the effects of progesterone on this parameter may depended on the time of the day at which it was administered. PMID- 7865873 TI - Effects of calcium and its antagonists on histamine-induced leakage in rat skin. AB - Evans blue extravasation in rat skin was used to study the effects of calcium, lanthanum, L-type calcium channel blockers and trifluoperazine on histamine induced leakage. Histamine effect was inhibited by calcium 1-2.5 mM, lanthanum 1 10 mM, nifedipine 0.1 and 1 microM and trifluoperazine 30 and 100 microM. The effects of calcium decreased progressively as its concentrations rose up to 10 mM. The association of nifedipine 0,1 microM or trifluoperazine 30 microM with calcium 3 microM increased the inhibitory effects. Calcium 10mM reversed the effect of nifedipine 0.1 microM but not that of lanthanum 1 mM or trifluoperazine 30 microM. It is proposed that the effect of calcium on histamine-induced leakage is the expression of a balance between an extracellular inhibitory effect and an intracellular enhancing effect. PMID- 7865874 TI - Allopregnant IgG binds and modulates the activity of uterine beta adrenoceptors. AB - Female Balb/c mice were mated to C3H male mice, to obtain an allopregnant IgG. This allopregnant IgG con activate beta-adrenoceptors of C3H uterus. Here we show that allopregnant IgG interacts with beta-adrenoceptors in uterus of C3H mice and produces a decrease of the spontaneous motility and an increase of the intracellular cAMP concentration. Both effects are blocked by propranolol, a beta adrenergic antagonist. Allopregnant IgG interferes with the binding of a specific beta adrenergic radioligand 3H-dihydroalprenolol behaving as a non competitive inhibitor. All these data indicate that allopregnant IgG could modulate the activity of uterine beta-adrenoceptors. PMID- 7865875 TI - The essential yeast Tcp1 protein affects actin and microtubules. AB - Previously, we showed that the yeast Saccharomyces cerevisiae cold-sensitive mutation tcp1-1 confers growth arrest concomitant with cytoskeletal disorganization and disruption of microtubule-mediated processes. We have identified two new recessive mutations, tcp1-2 and tcp1-3, that confer heat- and cold-sensitive growth. Cells carrying tcp1 alleles were analyzed after exposure to the appropriate restrictive temperatures by cell viability tests, differential contrast microscopy, fluorescent, and immunofluorescent microscopy of DNA, tubulin, and actin and by determining the DNA content per cell. All three mutations conferred unique phenotypes indicative of cytoskeletal dysfunction. A causal relationship between loss of Tcp1p function and the development of cytoskeletal abnormalities was established by double mutant analyses. Novel phenotypes indicative of allele-specific genetic interactions were observed when tcp1-1 was combined in the same strain with tub1-1, tub2-402, act1-1, and act1-4, but not with other tubulin or actin mutations or with mutations in other genes affecting the cytoskeleton. Also, overproduction of wild-type Tcp1p partially suppressed growth defects conferred by act1-1 and act1-4. Furthermore, Tcp1p was localized to the cytoplasm and the cell cortex. Based on our results, we propose that Tcp1p is required for normal development and function of actin and microtubules either through direct or indirect interaction with the major cytoskeletal components. PMID- 7865876 TI - Molecular characterization of Xenopus laevis DP proteins. AB - It is widely believed that in mammalian cells the cellular transcription factor (DRTF1/E2F integrates cell-cycle events with the transcription apparatus by interacting with important regulators of the cell cycle, such as the retinoblastoma gene product (pRb) and related proteins, cyclins, and cyclin dependent kinases. Here, we have defined DRTF1/E2F in Xenopus laevis that, like its mammalian counterpart, specifically binds to the E2F site, is regulated during development, and interacts with pRb and related proteins. We have isolated cDNAs that encode the functional homologue of mammalian DP-1, X1 DP-1, together with a close relative, X1 DP-2. X1 DP-1, which is highly conserved with murine DP 1, is a major DNA binding component of X1 DRTF1/E2F. Both DP-1 and DP-2 synergistically interact with members of the E2F family of proteins, E2F-1, E2F 2, and E2F-3, to generate DNA binding complexes that specifically recognize the E2F site and functionally interact with E2F-1 in E2F site-dependent transcriptional activation of cellular genes. DP-1 and DP-2 encode maternally stored transcripts that are expressed during early development. In the adult however, the expression of DP-1 and DP-2 is tissue restricted. This study therefore defines a new family of transcription factors, the DP proteins, members of which can interact combinatorially with E2F proteins to generate an array of DNA binding complexes that integrate cell-cycle progression with the transcription apparatus through the E2F binding site. The tissue-specific expression of DP family members suggests that the combination of DP/E2F heterodimers that constitute DRTF1/E2F is influenced by the phenotype of the cell. PMID- 7865878 TI - Molecular organization of transverse tubule/sarcoplasmic reticulum junctions during development of excitation-contraction coupling in skeletal muscle. AB - The relationship between the molecular composition and organization of the triad junction and the development of excitation-contraction (E-C) coupling was investigated in cultured skeletal muscle. Action potential-induced calcium transients develop concomitantly with the first expression of the dihydropyridine receptor (DHPR) and the ryanodine receptor (RyR), which are colocalized in clusters from the time of their earliest appearance. These DHPR/RyR clusters correspond to junctional domains of the transverse tubules (T-tubules) and sarcoplasmic reticulum (SR), respectively. Thus, at first contact T-tubules and SR form molecularly and structurally specialized membrane domains that support E C coupling. The earliest T-tubule/SR junctions show structural characteristics of mature triads but are diverse in conformation and typically are formed before the extensive development of myofibrils. Whereas the initial formation of T-tubule/SR junctions is independent of association with myofibrils, the reorganization into proper triads occurs as junctions become associated with the border between the A band and the I band of the sarcomere. This final step in triad formation manifests itself in an increased density and uniformity of junctions in the cytoplasm, which in turn results in increased calcium release and reuptake rates. PMID- 7865877 TI - TGN38 recycles basolaterally in polarized Madin-Darby canine kidney cells. AB - Sorting of newly synthesized plasma membrane proteins to the apical or basolateral surface domains of polarized cells is currently thought to take place within the trans-Golgi network (TGN). To explore the relationship between protein localization to the TGN and sorting to the plasma membrane in polarized epithelial cells, we have expressed constructs encoding the TGN marker, TGN38, in Madin-Darby canine kidney (MDCK) cells. We report that TGN38 is predominantly localized to the TGN of these cells and recycles via the basolateral membrane. Analyses of the distribution of Tac-TGN38 chimeric proteins in MDCK cells suggest that the cytoplasmic domain of TGN38 has information leading to both TGN localization and cycling through the basolateral surface. Mutations of the cytoplasmic domain that disrupt TGN localization also lead to nonpolarized delivery of the chimeric proteins to both surface domains. These results demonstrate an apparent equivalence of basolateral and TGN localization determinants and support an evolutionary relationship between TGN and plasma membrane sorting processes. PMID- 7865879 TI - Inhibition of endoplasmic reticulum (ER)-to-Golgi transport induces relocalization of binding protein (BiP) within the ER to form the BiP bodies. AB - Immunofluorescence staining of yeast cells with anti-binding protein (BiP) antibodies shows uniform staining of the endoplasmic reticulum (ER). We have found that overproduction of Sec12p, an ER membrane protein, causes a change of BiP distribution within the cell. Upon induction of Sec12p by the GAL1 promoter, the staining pattern of BiP turns into bright dots scattering in the cell, whereas the staining of Sec12p remains to be the typical ER figure. Overproduction of other ER membrane proteins, HMG-CoA reductase or Sed4 protein, does not induce such relocalization of BiP. Pulse-chase experiments and electron microscopy have revealed that the overproduction of Sec12p inhibits protein transport from the ER to the Golgi apparatus. When the transport is arrested by one of the sec mutations that block the ER-to-Golgi step at the restrictive temperature, the BiP staining also changes into the punctate pattern. In contrast, the sec mutants that block later or earlier steps of the secretory pathway do not induce such change of BiP localization. These observations indicate that relocalization of BiP is caused by the inhibition of ER-to-Golgi transport. Using immunoelectron microscopy, we have found that the punctate staining is because of the accumulation of BiP in the restricted region of the ER, which we propose to call the "BiP body." This implicates existence of ER subdomains in yeast. A vacuolar protein, proteinase A, appears to colocalize in the BiP body when the ER-to-Golgi transport is blocked, suggesting that the BiP body may have a role as the site of accumulation of cargo molecules before exit from the ER. PMID- 7865880 TI - Fission yeast minichromosome loss mutants mis cause lethal aneuploidy and replication abnormality. AB - Precise chromosome transmission in cell division cycle is maintained by a number of genes. The attempt made in the present study was to isolate temperature sensitive (ts) fission yeast mutants that display high loss rates of minichromosomes at permissive or semipermissive temperature (designated mis). By colony color assay of 539 ts strains that contain a minichromosome, we have identified 12 genetic loci (mis1-mis12) and determined their phenotypes at restrictive temperature. Seven of them are related to cell cycle block phenotype at restrictive temperature, three of them in mitosis. Unequal distribution of regular chromosomes in the daughters is extensive in mis6 and mis12. Cells become inviable after rounds of cell division due to missegregation. The phenotype of mis5 is DNA replication defect and hypersensitivity to UV ray and hydroxyurea. mis5+ encodes a novel member of the ubiquitous MCM family required for the onset of replication. The mis5+ gene is essential for viability and functionally distinct from other previously identified members in fission yeast, cdc21+, nda1+, and nda4+. The mis11 mutant phenotype was the cell division block with reduced cell size. Progression of the G1 and G2 phases is blocked in mis11. The cloned mis11+ gene is identical to prp2+, which is essential for RNA splicing and similar to a mammalian splicing factor U2AF65. PMID- 7865881 TI - Myotubes from transgenic mdx mice expressing full-length dystrophin show normal calcium regulation. AB - A lack of dystrophin results in muscle degeneration in Duchenne muscular dystrophy. Dystrophin-deficient human and mouse muscle cells have higher resting levels of intracellular free calcium ([Ca2+]i) and show a related increase in single-channel open probabilities of calcium leak channels. Elevated [Ca2+]i results in high levels of calcium-dependent proteolysis, which in turn increases calcium leak channel activity. This process could initiate muscle degeneration by further increasing [Ca2+]i and proteolysis in a positive feedback loop. Here, we tested the direct effect of restoration of dystrophin on [Ca2+]i and channel activity in primary myotubes from mdx mice made transgenic for full-length dystrophin. Transgenic mdx mice have been previously shown to have normal dystrophin localization and no muscle degeneration. Fura-2 calcium measurements and single-channel patch recordings showed that resting [Ca2+]i levels and open probabilities of calcium leak channels of transgenic mdx myotubes were similar to normal levels and significantly lower than mdx littermate controls (mdx) that lack dystrophin. Thus, restoration of normal calcium regulation in transgenic mdx mice may underlie the resulting absence of degeneration. PMID- 7865882 TI - Cell polarization directed by extracellular cues in yeast. PMID- 7865883 TI - Separation of v-Src-induced mitogenesis and morphological transformation by inhibition of AP-1. AB - v-Src activity results in both morphological transformation and reentry of quiescent chick embryo fibroblasts (CEF) into cell cycle. We have previously used temperature-sensitive v-Src mutants to show that enhanced activity of cellular AP 1 in the first few hours after activation of v-Src invariably precedes the biological consequences. Here we have investigated whether the early activation of AP-1 is essential for any or all of the v-Src responses by using a mutant c Fos that comprises the leucine zipper and a disrupted basic region. Expression of the c-Fos mutant partially reduced cellular AP-1 activity in exponentially growing cells. However, in CEF that had been made quiescent by serum deprivation, v-Src-induced stimulation of AP-1 DNA binding activity was substantially reduced. In addition, quiescent CEF stably transfected with this mutant show an impaired mitogenic response to v-Src, indicating that the AP-1 stimulation is a necessary prerequisite for cell-cycle reentry. The ability of v-Src to morphologically transform quiescent CEF was not impaired by the inhibition of AP-1 stimulation, indicating that the mitogenic and morphological consequences of v-Src have distinguishable biochemical mediators. Focal adhesion kinase, a recently identified determinant of cell morphology, undergoes a gel mobility shift, characteristic of its hyperphosphorylated state, in response to v-Src activation in cells expressing the inhibitory AP-1 protein. This provides further evidence that the pathways that regulate morphological transformation are independent of AP-1. PMID- 7865884 TI - Metabolic instability and constitutive endocytosis of STE6, the a-factor transporter of Saccharomyces cerevisiae. AB - STE6, a member of the ATP binding cassette (ABC) transporter superfamily, is a membrane protein required for the export of the a-factor mating pheromone in Saccharomyces cerevisiae. To initiate a study of the intracellular trafficking of STE6, we have examined its half-life and localization. We report here that STE6 is metabolically unstable in a wild-type strain, and that this instability is blocked in a pep4 mutant, suggesting that degradation of STE6 occurs in the vacuole and is dependent upon vacuolar proteases. In agreement with a model whereby STE6 is routed to the vacuole via endocytosis from the plasma membrane, we show that degradation of STE6 is substantially reduced at nonpermissive temperature in mutants defective in delivery of proteins to the plasma membrane (sec6) or in endocytosis (end3 and end4). Whereas STE6 appears to undergo constitutive internalization from the plasma membrane, as do the pheromone receptors STE2 and STE3, we show that two other proteins, the plasma membrane ATPase (PMA1) and the general amino acid permease (GAP1), are significantly more stable than STE6, indicating that rapid turnover in the vacuole is not a fate common to all plasma membrane proteins in yeast. Investigation of STE6 partial molecules (half- and quarter-molecules) indicates that both halves of STE6 contain sufficient information to mediate internalization. Examination of STE6 localization by indirect immunofluorescence indicates that STE6 is found in a punctate, possibly vesicular, intracellular pattern, distinct from the rim staining pattern characteristic of PMA1. The punctate pattern is consistent with the view that most of the STE6 molecules present in a cell at any given moment could be en route either to or from the plasma membrane. In a pep4 mutant, STE6 is concentrated in the vacuole, providing further evidence that the vacuole is the site of STE6 degradation, while in an end4 mutant STE6 exhibits rim-staining, indicating that it can accumulate in the plasma membrane when internalization is blocked. Taken together, the results presented here suggest that STE6 first travels to the plasma membrane and subsequently undergoes endocytosis and degradation in the vacuole, with perhaps only a transient residence at the plasma membrane; an alternative model, in which STE6 circumvents the plasma membrane, is also discussed. PMID- 7865885 TI - Effect of disruption of actin filaments by Clostridium botulinum C2 toxin on insulin secretion in HIT-T15 cells and pancreatic islets. AB - To examine their role in insulin secretion, actin filaments (AFs) were disrupted by Clostridium botulinum C2 toxin that ADP-ribosylates G-actin. Ribosylation also prevents polymerization of G-actin to F-actin and inhibits AF assembly by capping the fast-growing end of F-actin. Pretreatment of HIT-T15 cells with the toxin inhibited stimulated insulin secretion in a time- and dose-dependent manner. The toxin did not affect cellular insulin content or nonstimulated secretion. In static incubation, toxin treatment caused 45-50% inhibition of secretion induced by nutrients alone (10 mM glucose + 5 mM glutamine + 5 mM leucine) or combined with bombesin (phospholipase C-activator) and 20% reduction of that potentiated by forskolin (stimulator of adenylyl cyclase). In perifusion, the stimulated secretion during the first phase was marginally diminished, whereas the second phase was inhibited by approximately 80%. Pretreatment of HIT cells with wartmannin, a myosin light chain kinase inhibitor, caused a similar pattern of inhibition of the biphasic insulin release as C2 toxin. Nutrient metabolism and bombesin-evoked rise in cytosolic free Ca2+ were not affected by C2 toxin, indicating that nutrient recognition and the coupling between receptor activation and second messenger generation was not changed. In the toxin-treated cells, the AF web beneath the plasma membrane and the diffuse cytoplasmic F-actin fibers disappeared, as shown both by staining with an antibody against G- and F-actin and by staining F-actin with fluorescent phallacidin. C2 toxin dose-dependently reduced cellular F-actin content. Stimulation of insulin secretion was not associated with changes in F-actin content and organization. Treatment of cells with cytochalasin E and B, which shorten AFs, inhibited the stimulated insulin release by 30-50% although differing in their effects on F-actin content. In contrast to HIT-T15 cells, insulin secretion was potentiated in isolated rat islets after disruption of microfilaments with C2 toxin, most notably during the first phase. This effect was, however, diminished, and the second phase became slightly inhibited when the islets were degranulated. These results indicate an important role for AFs in insulin secretion. In the poorly granulated HIT-T15 cells actin-myosin interactions may participate in the recruitment of secretory granules to the releasable pool. In native islet beta-cells the predominant function of AFs appears to be the limitation of the access of granules to the plasma membrane. PMID- 7865886 TI - Nerve growth factor regulates the expression and activity of p33cdk2 and p34cdc2 kinases in PC12 pheochromocytoma cells. AB - In the absence of serum, nerve growth factor (NGF) promotes the survival and differentiation of the PC12 pheochromocytoma cell line. In the presence of serum, NGF acts primarily as a differentiation factor and negative regulator of cell cycling. To investigate NGF control of cell cycling, we have analyzed the regulation of cyclin dependent kinases during PC12 cell differentiation. NGF treatment leads to a reduction in the steady-state protein levels of p33cdk2 and p34cdc2, two key regulators of cell cycle progression. The decrease in p33cdk2 and p34cdc2 coincides with a decrease in the enzymatic activity of cyclinA p34cdc2, cyclinB-p34cdc2, cyclinE-p33cdk2, and cyclinA-p33cdk2 kinases. The decline in p33cdk2 and p34cdc2 kinase activity in response to NGF is accelerated in cells that over-express the p140trk NGF receptor, suggesting that the timing of the down- regulation is dependent on the level of p140trk and the strength of the NGF signal. The level of cyclin A, a regulatory subunit of p33cdk2 and p34cdc2, is relatively constant during PC12 differentiation. Nevertheless, the DNA binding activity of the cyclinA-associated transcription factor E2F/DP decreases. Thus, NGF down-regulates the activity of cyclin dependent kinases and cyclin-transcription factor complexes during PC12 differentiation. PMID- 7865889 TI - The American Society for Cell Biology 34th annual meeting. San Francisco, California, December 10-14, 1994. Abstracts. PMID- 7865887 TI - Nuclear mRNA accumulation causes nucleolar fragmentation in yeast mtr2 mutant. AB - We have identified a set of genes that affect mRNA transport (mtr) from the nucleus to the cytoplasm of Saccharomyces cerevisiae. One of these genes, MTR2, has been cloned and shown to encode a novel 21-kDa nuclear protein that is essential for vegetative growth. MTR2 shows limited homology to a protein implicated in plasmid DNA transfer in Escherichia coli. PolyA+RNA accumulates within the nucleus of mtr2-1 in two to three foci at 37 degrees C. mRNA, tRNA, and rRNA synthesis continue as do pre-mRNA splicing, tRNA processing, and rRNA export at 37 degrees C. Under these conditions the polyA tail length increases, and protein synthesis is progressively inhibited. Nucleolar antigens also redistribute to two to three nuclear foci at 37 degrees C, and this redistribution depends on ongoing transcription by RNA polymerase II. Surprisingly, these foci coincide with the sites of polyA+RNA accumulation. Comparable colocalization and dependance on RNA polymerase II transcription is seen for the mtr1-1 mutant. The disorganization of the nucleolus thus depends on mRNA accumulation in these mutants. We discuss the possible functions of MTR2 and the yeast nucleolus in mRNA export. PMID- 7865888 TI - PBP74, a new member of the mammalian 70-kDa heat shock protein family, is a mitochondrial protein. AB - The cloning of a cDNA encoding a new member of the highly conserved mammalian 70 kDa heat shock protein (hsp 70) family termed PBP74 was recently reported. Critical to an understanding of the function of this new hsp 70 is delineating its subcellular localization. Here we use a variety of immunological and biochemical approaches both in vitro and in vivo to demonstrate that PBP74 is imported into and resides in mitochondria. By confocal immunofluorescence microscopy PBP74 is detected in mitochondria, colocalizing with the mitochondrial 60-kDa heat shock protein. To address the inherent problem of serological cross reactivity among the hsp70 family members, an influenza virus hemagglutinin epitope tag was introduced into the PBP74 cDNA. The epitope-tagged PBP74 protein transiently expressed in L cells localized to mitochondria. Moreover, deletion of the N-terminal 46-amino acid presequence results in a cytosolic localization of the epitope-tagged protein. Cell fractionation studies demonstrated PBP74 in purified mitochondria in a protease-protected location. After coupled transcription-translation the precursor of PBP74 is imported into isolated yeast mitochondria, where it becomes processed to the mature protein. According to a subfractionation of the mitochondria, the imported protein was found to be localized in the matrix space. Import in vitro is time- and temperature dependent, requires matrix ATP, and is abolished upon depletion of the membrane potential across the mitochondrial inner membrane. Similarly, in mammalian cells PBP74 is synthesized as a pre-protein that requires membrane potential-dependent import into mitochondria for its maturation. Taken together, our data demonstrate that PBP74 is a mammalian mitochondrial hsp70. PMID- 7865890 TI - Enhanced susceptibility of the immune system to stress in morphine-tolerant rats. AB - The purpose of the present study was to determine the potential consequences to the immune system of the combined exposure of rats to stressor and morphine. Within 30 min following either morphine (5 mg/kg) injection or restraint stress (30 min) maximal analgesic responses as measured by tail-flick assay were observed. However, only morphine treatment was accompanied by a significant suppression (50%) in mitogen-stimulated lymphocyte proliferative responses. Restraint stress for either a 30-min or 2-h duration had no effect on lymphocyte responses. Exposure to a combination of restraint stress and acute morphine (5 mg/kg) resulted in a 50% suppression of lymphocyte responses which was similar in magnitude to that observed with morphine administration alone. When rats were injected twice daily for 4 days with increasing doses of morphine ranging from 10 mg/kg to 40 mg/kg, morphine (10 mg/kg) administration on Day 5 was not accompanied by either analgesia or depressed blood lymphocyte proliferative responses. These results indicated that tolerance had developed to both the analgesic and the immunosuppressive effects of morphine. However, upon exposure of morphine-tolerant animals to restraint stress, significant analgesic responses were retained. Furthermore, in contrast to the lack of suppression following restraint stress on lymphocyte responses in saline-injected animals, restraint for 30 min produced greater than a 70% suppression in morphine-tolerant animals. These data suggest that morphine tolerance may be accompanied by an enhanced susceptibility to the immunosuppressive effects of stress. PMID- 7865891 TI - Chronic morphine treatment suppresses CTL-mediated cytolysis, granulation, and cAMP responses to alloantigen. AB - Exposure to opioid drugs (e.g., morphine) in vivo has been shown to suppress natural killer cell activity. However, the effects of in vivo exposure to opioids on cytotoxic T lymphocyte (CTL) activity has not been investigated. The administration of morphine (50.0 mg/kg, sc) to alloimmunized mice for 11 days resulted in a significant decrease in peritoneal and splenic CTL activity. Moreover, the intracellular content of serine esterases and esterase release by CD8+ effector cells from chronic morphine-treated mice was reduced compared to that of effector cells from vehicle-treated controls. In addition, the CD8+ cAMP response to alloantigen was diminished compared to CD(8+)-enriched cells from vehicle-treated animals. However, conjugate formation between effector and target and subsequent killing of target by effector cells did not reveal significant differences between vehicle- and chronic morphine-treated animals. Serum corticosterone and dehydroepiandrosterone levels were significantly lower in the chronic morphine-treated animals while proopiomelanocortin gene expression (exon 3) in splenic lymphocytes did not correlate with morphine-mediated suppression of CTL activity. These results indicate that CTL activity is sensitive to chronic morphine exposure, implicating opioids as important cofactors during viral infections in suppressing cell-mediated immunity. PMID- 7865892 TI - Pavlovian conditioning of morphine-induced alterations of immune status: evidence for peripheral beta-adrenergic receptor involvement. AB - The present studies examined the involvement of peripheral beta-adrenergic receptor activity in the establishment and expression of conditioned morphine induced alterations of immune status. Previous work in our laboratory has shown that morphine's immunomodulatory effects can become conditioned to environmental stimuli which predict drug administration. These immune alterations include conditioned changes in natural killer cell activity, interleukin-2 production, and mitogen-induced lymphocyte proliferation. During the training phase of these experiments, Lewis rats received two conditioning sessions during which a subcutaneous injection of 15 mg/kg morphine sulfate was paired with exposure to a distinctive environment. On the test day, rats were reexposed to the conditioned stimulus prior to sacrifice. Saline or nadolol (0.002, 0.02, 0.2, or 2.0 mg/kg) was administered either prior to the training sessions or prior to the test session. Administration of nadolol prior to training did not affect the development of conditioned alterations of immune status. Conversely, nadolol administration prior to testing completely attenuated the expression of a subset of the conditioned morphine-induced changes in immune status. Taken together, these studies suggest that whereas peripheral beta-adrenergic receptor activity is not required for the establishment of conditioned morphine-induced alterations of immune status, it is involved in the expression of a subset of these conditioned immunomodulatory effects. PMID- 7865893 TI - Electrical stimulation of the dorsal midbrain periaqueductal gray suppresses peripheral blood natural killer cell activity. AB - This study examined the effects of dorsal midbrain periaqueductal gray (PAG) stimulation on both splenic and peripheral blood natural killer (NK) cell function as well as the proliferative response of lymphocytes to phytohemagglutinin mitogen. Male Sprague-Dawley rats were implanted with bipolar electrodes in the dorsal PAG. Following recovery, bipolar electrical stimulation eliciting a flight response was delivered at the rate of one/min for 30 min to freely moving rats. While dorsal PAG stimulation did not alter mitogen response or splenic NK activity, stimulation of this region of the PAG produced a marked decrease in peripheral blood NK response. In order to begin to explore a possible mechanism regulating suppression of peripheral blood NK activity, naltrexone (10 mg/kg) was administered prior to dorsal PAG stimulation. The results of this experiment replicated the findings that demonstrated suppression of peripheral blood NK following dorsal PAG stimulation. Naltrexone did not effect PAG induced suppression of peripheral blood NK. These findings point to the importance of the dorsal aspect of the PAG in the regulation of peripheral blood NK activity and further suggest that this phenomenon may not be opioid mediated. PMID- 7865894 TI - Both T cells and macrophages are targets of kappa-opioid-induced immunosuppression. AB - We have previously shown that antibody responses are inhibited following administration of kappa-opioid agonists. We found that the inhibition was blocked by either naloxone or the kappa-selective antagonist norbinaltorphimine. This inhibitory activity is apparent after short-term treatment with the kappa-opioid agonist. In an attempt to identify the cell populations which serve as the target for this immunosuppressive effect, we have carried out cell fractionation analyses to generate isolated T cells and macrophages. Using multiple cell fractionation methods, we have determined that short-term treatment of either T cells or macrophages with the kappa-opioid agonist U50,488H results in significant inhibition of in vitro antibody responses. We also find that the inhibition of both T cell and macrophage activity can be blocked by naloxone. These studies demonstrate that resting T cells and macrophages express kappa opioid receptors and exhibit significant opioid responsiveness prior to activation by antigen. PMID- 7865895 TI - The role of LGL/NK cells in surgery-induced promotion of metastasis and its attenuation by morphine. AB - Painful stress such as surgery has been shown both to suppress immune function and to promote metastasis, although the degree to which alterations in immunity underlies the tumor-enhancing effects of surgery remains unclear. We recently reported that an experimental laparotomy results in a twofold increase in the number of lung metastases following iv injection of MADB106 tumor cells, a natural killer (NK)-sensitive mammary adenocarcinoma cell line, syngeneic to the Fischer 344 rats we studied. Further, the administration of an analgesic dose of morphine prevented these metastatic-enhancing effects of surgery. The aim of the present study was to investigate the role of NK cells in both the metastatic enhancing effects of surgery and the attenuation of these effects by morphine. Using a simple 2 x 2 experimental design (surgery with anesthesia vs anesthesia only, and morphine vs vehicle), we found that surgery resulted in a decrease in both whole blood NK cytotoxic activity and number of circulating LGL/NK cells assessed 4 h postoperatively. In a second experiment involving an 18-h lung clearance assay, we used the mAb 3.2.3 to deplete rats of LGL/NK cells with the following rationale: if LGL/NK cells are necessary to mediate an event, then in their absence, that event should not occur. Normal and LGL/NK-depleted animals were assigned to the same four experimental groups, and radiolabeled MADB106 tumor cells were injected iv 4 h after surgery. In normal animals, there was a significant interaction between surgery and morphine such that morphine attenuated the surgery-induced increase in tumor cell retention without affecting tumor cell retention in the anesthesia groups. In the LGL/NK-depleted animals, however, although the tumor-enhancing effects of surgery remained evident, morphine did not mitigate this outcome. These results suggest that: (a) both LGL/NK cell activity and other factors independent of LGL/NK cells play a role in the surgery-induced increase in tumor cell retention; and (b) LGL/NK cells play a critical role in morphine's attenuating effects on this outcome. Finally, these results reinforce concern about the pathogenic consequences of unrelieved pain. PMID- 7865896 TI - Intermittent but not continuous inescapable footshock stress affects immune responses and immunocyte beta-endorphin concentrations in the rat. AB - It is well known that a variety of stressors influence immune responses. The opioid peptide-beta-endorphin (BE) is deeply involved in stress responses, is synthesized in cells of the immune system, and participates in the modulation of immune function. We analyzed the ability of two different stress paradigms to modulate the beta-endorphin concentrations in the immune cells and the immune response in the rat. Two and 24 h after the exposure to inescapable intermittent footshock (1.6 mA, 60 Hz, 1 s, every 5 s for 20 min) the concentrations of beta endorphin in splenocytes, peripheral blood mononuclear cells and lymph node cells were significantly increased. In contrast, the exposure to a continuous footshock for 3 min did not affect the concentrations of the opioid peptide. Similarly, phytohemoagglutinin-induced proliferation of splenocytes and natural killer activity were significantly impaired only after the exposure to intermittent footshock stress. On the contrary, plasma corticosterone levels were similarly elevated after both paradigms of stress. The pretreatment with the corticotropin releasing hormone (CRH) receptor antagonist prevented both the stress-induced increase of immunocyte BE and immunosuppression. In conclusion, our data suggest that intermittent and continuous footshock stressors activate different neuroendocrine responses and that CRH plays a central role in mediating the immune effects of the intermittent footshock stress. The possible relationship between the beta-endorphin changes and immunosuppression is discussed. PMID- 7865897 TI - Decreased beta-endorphin content in peripheral blood mononuclear leukocytes from patients with Crohn's disease. AB - Increased activation of lymphocytes in inflammatory bowel disease is reflected by alterations of various immunological functions including enhanced spontaneous secretion of rheumatoid factor by mononuclear cells. since in rheumatic diseases increased secretion of rheumatoid factor is associated with decreased levels of beta-endorphin in circulating blood mononuclear leukocytes, we investigated levels of leukocyte beta-endorphin in inflammatory bowel disease and compared them with those in hepatobiliary disorders and in healthy subjects. Levels of beta-endorphin were measured in extracts from peripheral blood mononuclear leukocytes by radioimmunoassay. beta-Endorphin levels ranged from 0 to 67 pg/10(6) cells. Mononuclear leukocytes from ulcerative colitis patients contained as much beta-endorphin as those from healthy control subjects. In patients with Crohn's disease, levels of beta-endorphin were reduced by as much as roughly 50%. An inverse relationship was found between leukocyte beta-endorphin on the one hand and erythrocyte sedimentation rate, blood granulocyte or thrombocyte counts, and C-reactive protein levels in plasma on the other. In patients with various hepatobiliary disorders including fatty liver disease, viral hepatitis, primary biliary cirrhosis, and cryptogenic or alcoholic cirrhosis, beta-endorphin levels were not significantly different from the normal range values. Data indicate that leukocyte beta-endorphin may be involved in regulation of the systemic inflammatory activity of Crohn's disease. PMID- 7865899 TI - Antisense phosphorothioate oligonucleotides direct both site-specific and nonspecific RNAse H cleavage of in vitro synthesized p120 mRNA. AB - To determine the sequence specificity with which various antisense phosphorothioate oligonucleotides to the p120 gene could direct RNAse H-dependent cleavage of p120 mRNA, an in vitro RNAse H assay was done on in vitro synthesized p120 mRNA. Three oligonucleotides tested (ISIS 3462, coding region; ISIS 3466, 3' untranslated region; and ISIS 3782, 3' untranslated region) directed cleavage of p120 mRNA at the target sites. In addition, several additional cleavage products from nontarget sites were detected. A computer sequence homology search revealed that these additional bands probably result from cleavage at regions of complementarity of eight or nine contiguous bases of the oligonucleotide and the p120 mRNA. These findings suggest that such nontarget specific cleavages may account for multiple effects of phosphorothioate oligonucleotides. PMID- 7865900 TI - Pharmacokinetics, tissue distribution, and stability of antisense oligodeoxynucleotide phosphorothioate ISIS 3466 in mice. AB - Phosphorothioate oligonucleotides have a potential as therapeutic agents. The pharmacokinetics, tissue distribution, stability, and cellular uptake by LOX ascites tumor of p120 antisense phosphorothioate oligonucleotide, ISIS 3466, were studied in vivo. The oligonucleotide, which was quickly cleared from the circulation in the normal mice after IV injection, was readily absorbed into the systemic circulation from the peritoneum. The oligonucleotide was found in most tissues 48 h after IP administration. The highest concentrations were in kidney and liver, but the brain had a very low concentration. The phosphorothioate oligonucleotide was intact even after 48 h. When the oligonucleotide was complexed with cationic lipid DOTMA, the DOTMA did not affect the oligonucleotide uptake or tissue distribution in normal mice. However, DOTMA significantly increased the oligonucleotide cellular uptake (4-10 times) in LOX ascites tumors in an IP/IP model. These results indicate that the phosphorothioate oligonucleotide is stable, has favourable kinetics for use as an therapeutic agent, and that DOTMA could be useful in local delivery of the oligonucleotide in vivo. PMID- 7865901 TI - Antitumor activity of nigericin and 5-(N-ethyl-N-isopropyl)amiloride: an approach to therapy based on cellular acidification and the inhibition of regulation of intracellular pH. AB - The extracellular pH (pHe) in solid tumors is frequently lower than the pHe in normal tissues, but the intracellular pH (pHi) is regulated to physiological levels. Cell killing can be achieved in an acidic environment in tissue culture by nigericin, which acidifies cells by transporting H+ from the extracellular space into the cytoplasm; this cell killing can be enhanced when used with 5-(N ethyl-N-isopropyl)amiloride (EIPA), a potent inhibitor of membrane-based Na+/H+ exchange, which plays a major role in the regulation of pHi (R. P. Maidorn; E. J. Cragoe; I. F. Tannock, Br. J. Cancer 67:297-303; 1993). We have therefore assessed the ability of nigericin and EIPA to kill cells in two murine solid tumors (the KHT fibrosarcoma and the EMT-6 sarcoma). Hydralazine, which reduces tumor blood flow, or glucose, which stimulates glycolysis leading to accumulation of lactate, were also administered to mice to lower pHe in the tumors. We observed only a small decrease in the surviving fractions of cells in the tumors when tolerated doses of nigericin and EIPA were given IP to tumor-bearing mice. When nigericin and EIPA were combined with administration of hydralazine, the surviving fraction of cells in both tumors was reduced by a factor of 0.01, but there were minimal effects on growth delay. Administration of glucose with nigericin and EIPA led to a smaller reduction in surviving fraction of the KHT tumor (by approximately 0.1), although glucose was more effective than hydralazine in lowering the mean tumor pHe. When KHT tumors were treated with 15 Gy X-rays followed immediately by nigericin, EIPA, and hydralazine, a reduced surviving fraction as well as an increase in tumor growth delay was observed compared to radiation alone; however, there was little evidence to suggest that these agents were selectively toxic to the cells that survived radiation. Nigericin and EIPA, with or without hydralazine, had minimal effects on normal tissues, as assessed by changes in body weight, number of leukocytes, and serum creatinine levels. We conclude that pharmacological effects to acidify cells and to prevent regulation of pHi under the acidic conditions that exist in solid tumors can lead to moderate levels of cell killing, if additional strategies are used to lower tumor pHe. PMID- 7865898 TI - Migration of neutrophils across endothelial monolayers is stimulated by treatment of the monolayers with beta-endorphin. AB - To study the effects of the cytokine and neuroendocrine hormone beta-endorphin on the transendothelial migration of neutrophils, bovine pulmonary artery endothelial cells were grown to confluence on PVP-free polycarbonate filters coated with gelatin. Pretreatment of endothelial cell cultures with 1 to 10 mumol/liter of beta-endorphin for 60 min resulted in significantly stimulated migration of subsequently added neutrophils across the endothelial monolayer. The number of neutrophils that migrated across beta-endorphin-treated endothelial cells was similar to the number that traversed untreated monolayers in response to gradients of formylpeptide. Consistently, an additive effect was seen when migration was induced by both beta-endorphin pretreatment of the endothelial cells and a formylpeptide chemotactic gradient. When used at optimal concentration, beta-endorphin was equally effective in stimulating neutrophil migration as was tumor necrosis factor-alpha. In the absence of formylpeptide the effect of apical surface exposure of endothelial cells to beta-endorphin versus basal surface exposure was comparable. Stimulation of neutrophil transendothelial migration in this system appeared to be specific and mediated by opiate receptors, since excess concentration of naloxone completely abolished the effect of beta-endorphin but not of tumor necrosis factor-alpha. These results suggest that beta-endorphin, released during stress, may act upon the endothelium to promote emigration of neutrophils from the vasculature. PMID- 7865903 TI - Reference Listings in Cancer Research. PMID- 7865904 TI - P-glycoprotein mediates profound resistance to bisantrene. AB - Bisantrene, mitoxantrone, and anthracyclines are anthracene derivatives that interact with DNA and are used for the treatment of cancers. The mechanisms of resistance to bisantrene are unknown. Here we show that cells that overexpress low levels of P-glycoprotein or are transfected with human MDR1 have approximately 10-fold greater resistance to bisantrene compared to vinblastine, doxorubicin, or colchicine. Furthermore, bisantrene can be used to select for high-level P-glycoprotein-mediated multiple drug resistance in a human colon carcinoma cell line, LS 174T, and the drug blocks photoaffinity labeling of P glycoprotein. The data suggest that bisantrene is an excellent substrate for P glycoprotein. These findings could influence subsequent clinical evaluation of bisantrene for the treatment of cancer. PMID- 7865902 TI - Schedule-dependent cytotoxicity of topotecan alone and in combination chemotherapy regimens. AB - The schedule-dependent cytotoxic effects of topotecan were evaluated in tissue culture experiments with Chinese hamster V79 cells. One hour exposure to topotecan resulted in a typical phase-specific cell killing curve in which increasing concentrations kill progressively more cells and then reach a plateau when all susceptible cells are killed. In contrast, exposure for 24 h results in a steep concentration-response curve with no plateau. Other S-phase agents such as hydroxyurea or aphidicolin antagonized cytotoxicity when administered by simultaneous exposure with topotecan. Combinations of melphalan, BCNU (1,3 bis(2 chloroethyl)-1-nitrosourea), or cisplatinum with topotecan were most effective when cells were exposed to the alkylating agent or platinating agent during the first hour of a 24-h topotecan exposure. Combinations of topotecan with etoposide or adriamycin produce more cytotoxicity when topotecan is administered by prolonged exposure; however, there is no significant difference depending on whether the topoisomerase II inhibitor is added at the beginning or end of the topotecan exposure. These studies show the importance of appropriate dose scheduling to obtain optimal interaction of chemotherapeutic agents given in combination with topotecan. PMID- 7865905 TI - Flow cytometric analysis of cell-killing actions of 5-fluorouracil in human colorectal cancer cells. AB - To confirm our previous kinetic analysis of the mode of cell-killing action of 5 fluorouracil (5-FU), we carried out a flow cytometric analysis with human colorectal cancer DLD-1 cells. Cells were treated with each cytotoxic concentration of 5-FU for 1 or 72 h, and the periodic changes in flow cytometric pattern were compared with those of 5-fluorouridine (FUrd) and 5-fluoro-2' deoxyuridine (FdUrd). When cells were cultured with 5-FU for 72 h, most of them accumulated in S phase and remained there. This pattern was the same as that seen in cells that were continuously exposed to FdUrd. In contrast, when cells were exposed to 5-FU for 1 h and cultured in drug-free medium, they ended the cell cycle traverse in either G2/M or G1 phase after an immediate but transient accumulation in S phase. Results were identical to those observed with cells similarly treated with FUrd. These results demonstrated a good accordance with those of our kinetic analysis, and strongly suggested that the mode of cell killing exhibited by 5-FU differs with exposure time: 5-FU acts like FUrd in short exposure conditions, and it acts similarly to FdUrd in continuous exposure conditions. PMID- 7865906 TI - Inhibition of MDR1 gene expression by antimessenger oligonucleotides lowers multiple drug resistance. AB - The multiple drug resistance of neoplastic cells is mediated by overexpression of the human MDR1 gene, which encodes the transmembrane efflux pump P-glycoprotein. In both cell lines and human tumors the MDR phenotype closely correlates with MDR1 mRNA and P-glycoprotein levels. Reversion of the MDR phenotype was attempted in human colorectal adenocarcinoma doxorubicin (Dx)-resistant cells (Lo Vo/Dx) by long-term administration of an equimolecular mixture of three unmodified ODNs (18mer) targeted to adjacent binding sites of the MDR1 mRNA and carried by a synthetic cationic lipid (DOTAP). Three different experimental parameters were used to evaluate the antimessenger agent's effectiveness in comparison with a random sequence ODN: the level of cell resistance to Dx; the level of P glycoprotein (determined by flow cytometry); the level of MDR1 mRNA (determined by quantitative RT-PCR). Experimental data indicate that the level of both the MDR1 mRNA and the P-glycoprotein is reduced by approximately 50% by treatment of Lo Vo/Dx cells with a 10 microM total concentration of the aODN mixture every 24 h for 15 days. In agreement with these findings, sensitivity to Dx of the antimessenger agent-treated Lo Vo/Dx cells was almost doubled in comparison with random sequence ODN-treated controls. PMID- 7865907 TI - Procoagulant activity in cancer cells is dependent on tissue factor expression. AB - Procoagulant activity of pairs of cell lines, which were derived from the same original cell type but which possess different growth characteristics and metastatic properties, was examined. The following characteristics were considered suggestive of a greater likelihood of metastatic potential: high histological grade; establishment of the line from a metastatic rather than a nonmetastatic cancer; increased tumorigenicity in nude mice; and/or estrogen receptor-negative mammary cancer. Procoagulant activity was evaluated by a two stage clotting assay. Procoagulant activity was highly variable, with up to a 1,300-fold difference, among the cancer cell lines examined. The rate of clot formation was factor VII dependent and was totally inhibited by an anti tissue factor monoclonal antibody, indicating that tissue factor was the only significant procoagulant present in these cancer cells. Tissue factor antigen expression, evaluated by ELISA, correlated with procoagulant activity. In all pairs of cancer cell lines, those with characteristics of increased proliferative potential had increased tissue factor levels compared to cell lines that originated from the same cell type, but which possess less aggressive characteristics. Tissue factor activity in these cancer cells was increased by cell lysis or by exposure of intact cells to a calcium ionophore, similar to results previously obtained in fibroblasts. Tissue factor mRNA was evaluated by northern blot analysis using a specific probe complementary to tissue factor mRNA. The previously described predominant tissue factor mRNA species of 2.2 kb was identified in the majority of cancer cell lines examined, but tissue factor mRNA species of 3.2 to 3.4 kb were also identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865909 TI - Reference listings in cancer research. PMID- 7865908 TI - Quantitative analysis of folylpolyglutamate synthetase gene expression in tumor tissues by the polymerase chain reaction: marked variation of expression among leukemia patients. AB - Evidence from previous in vitro studies indicates that the enzyme folylpolyglutamate synthetase (FPGS) may be an important determinant of the antitumor activity of antifolate drugs that are substrates for this enzyme. To facilitate investigations regarding the association between FPGS content of tumor tissues and the sensitivity of tumors to antifolates, we developed a polymerase chain reaction (PCR)-based gene expression quantitation assay for measuring relative amounts of FPGS mRNA in tumor tissue specimens. From the known sequence of the human gene, FPGS-specific PCR primers were chosen that flanked a 263-base segment of the FPGS gene. The PCR carried out with these primers was linear over at least a three orders of magnitude range of starting cDNA concentration. The amount of cDNA required per assay corresponded to the quantity of RNA contained in nanogram to microgram amounts of tissue, depending on the level of gene expression. In CHO AUXB1 (FPGS) cell lines transfected with human DNA and expressing different levels of human FPGS, FPGS gene expression measured by this assay was linear with the FPGS enzyme activity in the cells. In human head and neck cell lines, which contained naturally varying levels of FPGS enzyme activity, FPGS gene expressions were also linearly proportional to FPGS enzyme content as measured both by activity in cell-free extracts and by intracellular methotrexate polyglutamate formation. Among leukemic cells from 11 acute lymphocytic leukemia and acute myelogenous leukemia patients, FPGS expression varied by over 500-fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865910 TI - Pneumocystis carinii pneumonia after liver transplantation in adults. AB - Proven Pneumocystis carinii pneumonia (PCP) occurred in 8 (5.2%) of 154 adult liver transplant recipients between January 1986 and December 1992. The interval between transplantation and PCP ranged from 69 to 131 days with a mean of 95 days (SD 20 days). The PaO2 breathing room air at diagnosis ranged from 40 mmHg to 75 mmHg with a mean of 59.6 mmhg (SD 13 mmHg). Bronchial washings taken at bronchoscopy stained positively for Pneumocystis carinii and confirmed the diagnosis. Transbronchial biopsy was unnecessary for diagnosis. One patient died from PCP while the remainder recovered. Patients transplanted immediately before the index patients served as controls. Patients who developed PCP had more episodes of rejection (p < 0.05), received more OKT3 (p < 0.05), and were receiving more prednisone (p < 0.05) than controls. They also had lower levels of albumin (p < 0.01), and higher levels of alkaline phosphatase (p < 0.05), alanine (p < 0.01), and aspartate aminotransferase (p < 0.001), and gamma glutamyltranspeptidase (p < 0.02). This study raises the possibility of selecting patients at risk of PCP for chemoprophylaxis. PMID- 7865911 TI - Complications of ureterovesical anastomosis in kidney transplant patients: the Minnesota experience. AB - We reviewed urologic complications of 1183 consecutive primary or secondary renal transplants performed with bladder anastomoses at the University of Minnesota Hospital between 1985 and 1993. The Politano-Leadbetter (PL) technique of ureteroneocystostomy was used in 410 patients; the multistich (MS) extravesical technique modified from the methods of Witzel, Sampson, and Lich in 295; and the extravesical single-stitch (SS) technique in 478. Urologic complications occurred in 81 patients (6.8%). Of these complications, 68 (5.7%) were early (< 4 months) and 13 (1.1%) late; 32 (7.8%) were after PL, 17 (5.8%) after MS, and 32 (6.7%) after SS. A total of 13 patients had an anastomotic leak, 7 (1.7%) after PL, 4 (1.4%) after MS, and 2 (0.0004%) after SS; 49 patients had a ureterovesical obstruction, 16 (4.0%) after PL, 12 (4.0%) after MS, and 21 (4.2%) after SS; 5 patients had a ureteropelvic obstruction, 2 (0.5%) after PL, 2 (0.7%) after MS, and 1 (0.2%) after SS; and 14 patients had hematuria, 7 (1.7%) after PL, 1 (0.34%) after MS, and 6 (1.3%) after SS. Of the 81 patients with urologic complications, one (1%) resolved spontaneously; 30 (37%) were treated with temporary percutaneous nephrostomy, 17 (21%) with dilatation and stent; the 14 (17.3%) with hematuria were treated via cystoscopy; 19 (23%) required reoperation. Only 2 (2.5%) patients lost their graft. For both cadaver and living donor recipients, there was no difference between techniques for early and late complications of leakage, stricture, and hematuria. Each technique has certain advantages and each should be in every surgeon's repertoire. PMID- 7865912 TI - The effect of rabbit antithymocyte serum (RATS) and OKT3 on peripheral blood mononuclear cell subsets following renal transplantation. AB - Fifty-five renal transplant recipients were studied prospectively for changes in monoclonal antibody-defined mononuclear cell subsets (MCS) over the first 45 days posttransplant. Patients received induction immunotherapy with either monoclonal OKT2(n = 29) or polyclonal RATS (n = 26) preparation. Sequential examinations showed characteristic patterns of MCS depletion, which differed according to the type of therapy received and which subset was examined. In general, induction therapy with RATS resulted in greater and more sustained reduction of most MCS than was seen with OKT3 therapy. In recipients who received OKT3 induction there was a correlation between allograft rejection and an increase in lymphocytes expressing pan-T cell markers and in natural-killer cells. In contrast, rejection episodes in patients receiving RATS were associated with increases in subpopulations of T cells including helper, inducer and suppressor/cytotoxic T cell subsets. There was no correlation of rejection with B cells or T-cell activation markers. The different patterns of MCS depletion with different antilymphocyte preparations and the association between changes in different MCS and rejection warrant further investigation. PMID- 7865913 TI - Should elderly donors be accepted in a live related renal transplant program? AB - It is a matter of concern that the elderly donor may have increased risks in the peri-operative period due to age-related changes in various organ. Nephrosclerosis, atherosclerosis and low GFR of an elderly kidney may portend a poor graft outcome. A retrospective analysis of our live related renal transplant program (from June 1989 to December 1993) revealed that 27 of the donors were above 60 years of age. 21 of the recipients have been followed up for more than 1 year. These patients were compared with a cohort of 25 patients (donor age < 45 years) with similar HLA match, immunosuppressive protocol, and follow-up period more than 1 year. Graft survival at 1 year was 86% and 88% in the recipients from elderly and younger donors respectively; 1 patient in the control group died of fulminant sepsis. Mean follow-up was 21.6 months in the study group and 22.8 months in the control group. Allograft function was evaluated by serum creatinine and differential GFR by Tc DTPA scan. Serum creatinine (mg%) was 1.3 +/- 0.2 and 1.4 +/- 0.2 in the study group and 1.3 +/- 0.3, 1.2 +/- 0.3 in the control group at 3 and 12 months respectively. Glomerular filtration rate (ml/min) was 36.5 +/- 11.6 and 43.7 +/- 12.4 in the recipients from elderly donors whereas those from the younger donors had GFR (ml/min) of 40.6 +/- 9.6 and 49.6 +/- 14.2 at 3 and 12 months respectively, GFR continued to improve in both groups with follow-up. There was no difference in incidence or severity of ATN In the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865914 TI - Increased incidence of rejection in patients with delayed graft function. AB - Because of the difficulties in diagnosing rejection in patients with delayed graft function, such patients were routinely biopsied 7-10 days after kidney transplantation. We found histologic evidence of rejection in 48% of the cases during the lst month posttransplant, a proportion that was significantly higher than in patients with immediate graft function. Furthermore, the 2-year graft survival in patients with delayed graft function and rejection, but not in those without rejection, was significantly lower than in patients with immediate function. The results suggest that there is an association between delayed graft function and rejection and that rejection is the component responsible for the decreased graft survival previously reported for patients with delayed graft function. PMID- 7865915 TI - New medical technologies and clinical practice: a survey of lymphocyte subset monitoring. AB - BACKGROUND: Since its inception in the early 1980s, lymphocyte subset (LS) monitoring of transplant patients has been a controversial technique. The clinical literature is replete with contradictory claims concerning its usefulness. No systematic information is however available on clinicians' attitudes towards the new technology. METHOD: We carried out a mail survey of the members of The Transplantation Society concerning the availability, use, value, and critical assessment of LS monitoring. RESULTS: Results show that LS monitoring technology is available in most clinical settings surveyed and is regularly used by about half of the respondents associated with a clinical transplant program. About half of the users obtain diagnostically relevant measurements (T4/T8 ratios), as opposed to measurements related to OKT3 anti rejection therapy. While claiming that LS measurement is a useful tool, respondents attribute a low average score to the diagnostic value of the technique; about 2/3 believe that its absence would not affect their clinical judgment. Finally, 25% of the respondents send blood for LS measurements although they do not believe the technique is useful. CONCLUSIONS: The results suggest that research instruments which generate clinical interest may develop clinical diagnostic routines despite a lack of consensus concerning their usefulness. More importantly, these routines avoid a critical assessment of key notions such as "immune monitoring" which tend to blur the distinction between research and therapy. PMID- 7865916 TI - Influence of oral felodipine on serum cyclosporine concentrations. AB - Hypertension and nephrotoxicity are frequent in renal transplant patients treated with cyclosporine. Calcium-channel blockers, because of their vasodilatory effects on the renal afferent arteriole, may be the anti-hypertensive agents of choice in this population. Unfortunately, many calcium channel blockers inhibit the clearance of cyclosporine, resulting in elevated blood levels, and worsening nephrotoxicity. Thirteen hypertensive renal transplant patients, on stable cyclosporine doses and with stable cyclosporine blood levels, had felodipine added to their antihypertensive regimens. The effect on cyclosporine level was measured. Mean trough serum cyclosporine concentration increased slightly, from 122.8 +/- 51.8 ng/ml to 143.1 +/- 81.9 ng/ml with chronic felodipine administration (p = NS). Mean systolic and diastolic pressures both fell significantly, by approximately 10 mmHg (systolic from 161 +/- 14 to 152 +/- 13 mmHg; diastolic from 100 +/- 6 to 90 +/- 7 mmHg). Serum creatinine remained unchanged. Four patients eventually discontinued felodipine. There was no significant change in their mean trough serum cyclosporine concentration when felodipine was discontinued. Thus, felodipine is an effective anti-hypertensive medication in cyclosporine-treated renal transplant recipients, without significant effect on cyclosporine blood levels, or adverse effect on allograft function. PMID- 7865917 TI - Recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients: successful treatment with oral cyclophosphamide. AB - Focal segmental glomerulosclerosis (FSGS) is the most common glomerulopathy leading to end-stage renal disease in children and transplantation is complicated by recurrent disease in a significant percentage of children. Treatment of recurrent FSGS has included high-dose steroids, high-dose cyclosporine (CSA), plasmapheresis, and ACE inhibitors with mixed results. We have had a consistent approach using oral cyclophosphamide (CTX) to treat recurrent FSGS since 1982. Three patients with ESRD secondary to nephrotic syndrome had recurrent disease. Biopsies in all 3 were consistent with recurrent FSGS. Patients were begun on a 8 12 week course of 1-2 mg/kg/day of CTX and dosage was adjusted for WBC count. Azathioprine was with held during CTX. Patients' dosage at the end of 12 weeks ranged from 0.89-1.75 mg/kg/day. All patients tolerated CTX well. After 8-12 weeks of treatment, 2 patients with nephrotic syndrome normalized their serum albumin and had negative to trace protein on urinary dipstick. One patient with proteinuria decreased his protein excretion from 770 to 340 mg/m2/day. At follow up at 8, 38, and 125 months post-transplant, these 3 patients have stable graft function and negative to trace protein on urinalysis. The patient followed for 125 months has had 2 additional relapses at 51 and 82 months post-transplant that were treated successfully with pulse intravenous steroids. Three pediatric patients with recurrent focal segmental glomerulosclerosis post-renal transplant were treated with oral CTX and had significant improvement in proteinuria and preservation of graft function. This suggests that oral CTX is a potentially effective and well-tolerated treatment for recurrent FSGS in children. PMID- 7865918 TI - Correlates of noncompliance among renal transplant recipients. AB - The purpose of this study was to identify variables that are associated with noncompliance among adult renal transplant recipients, including demographic characteristics, transplant-related variables, and psychosocial factors. The measurement of noncompliance was improved by assessing noncompliant behaviors (i.e., noncompliance with medications and the follow-up regimen) prior to the onset of complications and/or graft loss and by measuring compliance as a continuous rather than dichotomous variable. Two-hundred-and-forty-one renal transplant recipients completed the Beck Depression Inventory, the anxiety and hostility subscales of the Brief Symptom Inventory, the Multidimensional Health Locus of Control Scale, the Inventory of Socially Supportive Behaviors, the Coping Strategies Inventory, a measure of transplant-related stressors, and self report measures of compliance with medications and the follow-up regimen. Approximately half of our sample reported at least some degree of noncompliance. Recipients who were younger, female, unmarried, retransplanted, and with lower incomes tended to be noncompliant with medications (all p's < 0.05). Recipients who were unmarried, low income, not insulin-dependent, and with a longer time since transplant tended to be noncompliant with the follow-up regimen. In addition, recipients who reported higher stress and more depression, who coped with stress by using avoidant coping strategies, and who believed that health outcomes are beyond their control were less compliant with both medications and follow-up (all p's < 0.05). Regression analyses revealed that stress was the strongest predictor of both medication and follow-up compliance. PMID- 7865919 TI - Case studies of pronoun development in two hearing-impaired children: normal, delayed or deviant? AB - This paper is a study of first and second person pronoun development in the spoken language of two young hearing-impaired children. Pronoun development was examined over a period of 11 months, starting at the age of 29 and 28 months, to determine whether the children's acquisition of these pronouns would reflect normal, delayed or deviant patterns of development. Comparison of data from these children with data regarding normally developing children shows the hearing impaired children's acquisition to be within normal expectations for hearing age and overall linguistic level, and only slightly delayed in terms of chronological age. These results lend support to the view that differences in the hearing impaired child's language ability are probably the result of a relative lack of auditory and linguistic experience, rather than reorganisation of the hearing impaired child's psychological and cognitive processing abilities. PMID- 7865920 TI - Parental-based intervention with pre-school language-delayed children. AB - Mothers of children randomly allocated to an experimental group attended fortnightly group parental language training sessions, over a 6-month period. Mothers of children allocated to a matched no intervention control group received no special attention. The results showed significantly greater gains in the expressive language skills of the experimental group compared to the control group. A second experiment was designed to compare the parental involvement approach with direct, individual treatment and to clarify the role of non specific 'Hawthorne-type' effects. The experimental group mothers attended parental language training sessions, as above. The parental control group mothers also attended training sessions, with the emphasis on general learning skills rather than language. A third group of children received individual, direct speech and language therapy. Results showed significantly greater language gains in the parental language training group and in the individual group in comparison with the non-specific training group. The two former groups did not differ significantly, indicating that, for these groups and this methodology, parental language training is as effective as individual speech and language therapy. The results also indicate that the effectiveness of the parental involvement approach cannot be accounted for by non-specific factors. The research findings are discussed, together with the professional implications of the study and recommendations for further research. PMID- 7865921 TI - Speech studies and the unoperated cleft palate subject. AB - This paper is a critical review of the studies of patients who have established their speech in the presence of an unoperated cleft palate. The review details the weaknesses of many of the studies in this area, and in so doing highlights the methodological issues that need to be considered in the investigation of cleft palate speech. For example, issues such as the method of speech analysis and the importance of reliability studies are discussed. The need to control for variables such as age at palatal surgery, cleft type and patients' surgical experience is highlighted. Such principles are equally applicable to those studies in which palatal surgery is carried out at more conventional ages. more conventional ages. PMID- 7865922 TI - Is 20 years too long?: improving intelligibility in long-standing dysarthria--a single case treatment study. AB - Resource management decisions by most speech and language therapists would suggest that treatment for a dysarthric client of 20 years' duration should be a low priority. This study describes the therapy of a dystonic client who had been virtually speechless for 20 years because of his severe dysarthria. Assessment of his speech revealed that lip rounding was particularly difficult for him. He was offered eight sessions of general dysarthria therapy and eight sessions of therapy specifically designed to reduce lip tension. The hypotheses driving this therapy plan were that it would be possible to effect changes in his longstanding speech patterns and that therapy focused on reducing lip tension would be more effective than non-specific dysarthria therapy. An intelligibility test was designed to monitor any changes in his speech production. Therapy improved the client's intelligibility and increased his confidence and consequent functional use of speech. PMID- 7865923 TI - Following the dolphins: an ethnographic study of speech and language therapy with people with learning difficulties. AB - The purpose of this study was to examine speech and language therapists' practices, and their perceptions of the knowledge and skills that they use in everyday clinical practice. The paper compares the knowledge and skills identified in a much larger consultative study of speech and language therapists' competence with the knowledge and skills identified by four speech and language therapists reflecting on a representative or 'typical' day in their working lives. This comparison between the outcome of a large survey and a more detailed ethnographic investigation of speech and language therapists' competence confirmed earlier reports that speech therapy appears to have a broad knowledge and skills base. Ethnographic analysis also revealed that this broad knowledge and skills base was, in the main, highly relevant to everyday clinical practices. PMID- 7865924 TI - Speech by any other name: the role of communication aids in interaction. AB - The functional communication systems of four physically disabled children with severe speech impairment were evaluated in terms of: (1) perceived dominant modes of communication; (2) observed frequency of communication mode occurrence; and (3) role of communication device in total communication system. All four subjects used a range of communication modes to reflect personal and listener preferences, and in response to differing conversational requirements. 'Standard' communication modes were mentioned more frequently by teachers and parents, and were observed more frequently in interactions. Augmentative and alternative communication devices played a limited but important role within total communication systems. A hierarchy of influences affecting the choice of communication mode is suggested. PMID- 7865925 TI - An analysis of the communication of adult residents of a long-term care hospital as perceived by their caregivers. AB - Different groups of caregivers (nurses, orderlies, professionals, student orderlies and volunteers) who were in frequent interaction with residents from a long-term care hospital were interviewed with a nominal group process. They were asked to identify concrete situations of communication in which residents with no trouble communicating, residents with aphasia and residents with dementia need to express and/or comprehend a message. A total of 196 statements were recorded and coded using a qualitative approach into different categories of communication acts specific to daily life situations and several categories of generic communication acts, which are unrelated to the daily routine of care and treatment. The results show that communication in daily life situations varies little in relation to the different residents. However, residents with language disorders are perceived to be less involved in generic communication acts than residents with no communication disorder. They also demonstrate that the perceptions of communication of the different caregivers vary. The results are discussed in relationship to the conception of an evaluation instrument for language-impaired long-term care residents, which will help in determining intervention as well as the objective evaluation of its effects. PMID- 7865926 TI - Conversation as therapy for older adults in residential care: the case for intervention. AB - Social isolation resulting from sensory loss tends to reduce life satisfaction in older adults. Residence in a long-term care facility such as a nursing home does little to alleviate their communication needs. Potenial communication partners are available (e.g. other residents, family and friends, nursing staff, volunteers, health-care workers), but many need instruction, counselling and feedback to become therapeutically effective. The speech pathologist's experience as both communication therapist and social facilitator can enhance consultation and staff training in this area. PMID- 7865927 TI - The variability of language test scores in 3- and 4-year-old children of normal non-verbal intelligence: a brief research report. AB - Language testing plays an important role in the identification and monitoring of children with communication difficulties. However, the standardisation of many tests in common use remains far from satisfactory, especially at the lower age ranges. Comparisons between age-equivalent scores and chronological age also raise particular problems. The present paper focuses on the disparity between scores on different tests, in spite of the homogeneity of the group of children studied, and stresses the need for caution in the interpretation of test scores. PMID- 7865928 TI - Chronic back pain: integrating psychological and physical therapy--an overview. AB - Chronic back pain is a major consumer of costly healthcare resources in the Western world. Patients' suffering affects their families and associates, leads to diminished self-confidence, and prevents their effective participation in the workplace. Although medical treatments and analgesics are generally successful in treating acute back pain, and some patients recover spontaneously, conventional approaches are less successful in dealing with chronic pain and may be contraindicated. In the first of two articles, the author offers an overview of research on cognitive-behavioral programs, using operant activity and relaxation training, that have led to reductions in patients' pain and to increases in their activity levels. Part 2 provides a step-by-step description of how to incorporate basic psychological techniques and physical therapy procedures for chronic pain sufferers. Patient and therapist cooperate in operant activities, with the patient monitoring progress and carrying out regular home-work assignments as he or she seeks to perform target activities; applied relaxation encourages the patient to cope with pain by disrupting the connection between anxiety, despair, and pain. The techniques outlined are suitable for dealing with other musculoskeletal conditions as well as with chronic back pain. PMID- 7865929 TI - Chronic back pain: activities training and physical therapy. PMID- 7865930 TI - Chronic back pain: behavioral interventions and outcomes in a changing healthcare environment. PMID- 7865931 TI - An expanded view of health: implications for how healthcare works. PMID- 7865932 TI - Effectiveness of a videotaped behavioral intervention for dental anxiety: the role of gender and the need for information. AB - The authors evaluated the effectiveness of a videotaped behavioral treatment program in reducing dental anxiety. They compared patients who witnessed the intervention videotape with patients who saw a placebo program and with a no treatment control group. The subjects were 66 patients who visited a dentistry clinic for prophylaxis and general dental treatment. Groups were balanced for gender and level of preference for information as measured by the Krantz Health Opinion Survey--Information subscale. Self-report, physiological, and observed behavioral measures were assessed at specified times. Results demonstrated significant Group X Gender interaction effects during the different assessment periods, with men responding best to the treatment videotape, whereas women responded best to the placebo videotape. The level of information preference was found to a be a significant contributing factor at certain assessment periods. Overall, these results suggest that preparatory videotaped interventions are particularly effective in decreasing dental anxiety when patient characteristics are matched with characteristics of the intervention. PMID- 7865933 TI - Pressor reactivity, ethnicity, and 24-hour ambulatory monitoring in children from hypertensive families. AB - We assessed blood pressure responses of a multiethnic (Black and White) sample of 120 children of hypertensive families to orthostasis, video game, forehead cold, and dynamic exercise, and monitored the children's ambulatory pressure 24 hours later. Thirteen children were studied twice (1-year stability). The Black children exhibited higher 24-hour ambulatory systolic and diastolic pressures than the White children. Regardless of ethnicity, peak and mean systolic pressures during each task were generally positively correlated with mean systolic pressure while the children were awake and asleep. Associations between diastolic pressor responses and ambulatory measurements were somewhat dependent upon ethnicity and task. Relatively few reactivity-ambulatory correlations were significant, using pressor reactivity change scores. The children who participated twice exhibited significant 1-year stability for most ambulatory and pressor measurements. Children's pressor responses to laboratory tasks may generalize to the natural environment. PMID- 7865934 TI - Comparison of breath-hold T1-weighted MR sequences for imaging of the liver. AB - Three rapid T1-weighted gradient-echo techniques for imaging of the liver were compared: fast low-angle shot (FLASH) and section-selective (SSTF) and non section-selective (NSTF) inversion-recovery TurboFLASH. Ten healthy volunteers were imaged at 1.5 T, with breath-hold images acquired in the transaxial and coronal planes and non-breath-hold images in the transaxial plane. Breath-hold images were evaluated quantitatively and qualitatively, and non-breath-hold images were evaluated qualitatively. FLASH images had significantly higher (P < .001) spleen-liver signal difference-to-noise ratios (SD/Ns) than NSTF and SSTF images. Liver signal-to-noise ratios (S/Ns) were significantly higher (P < .001) on FLASH images than on NSTF and SSTF images. With breath hold, FLASH images were rated as having the highest quality in the axial plane, followed by NSTF and SSTF images. In the coronal plane, NSTF images were rated as having the highest quality. For images acquired during patient respiration, NSTF images had the highest quality and showed the least degradation. The results suggest that FLASH images have the highest SD/N and S/N for liver imaging and have the highest quality in the axial plane. In patients who cannot suspend respiration. NSTF images may be least affected by breathing artifact and provide reasonable image quality. PMID- 7865935 TI - MR portography: preliminary comparison with CT portography and conventional MR imaging. AB - Magnetic resonance (MR) imaging with arterial portography (MRAP) was compared with computed tomography with arterial portography (CTAP) and conventional MR imaging for preoperative evaluation of hepatic masses in eight patients (nine studies). Twenty contiguous, 10-mm-thick-section CTAP images were obtained. MR imaging included T1- and T2-weighted spin-echo and fast multiplanar SPGR (spoiled gradient-recalled acquisition in the steady state) techniques. For MRAP, 0.1 mmol/kg gadopentetate dimeglumine was injected into the superior mesenteric artery. Portographic-phase, 8-mm-thick-section, axial SPGR images were first obtained, followed by "systemic phase" SPGR images. Lesions were seen best on the portographic-phase MRAP images and were less conspicuous on the systemic-phase MRAP, CTAP and conventional MR images. Of 19 visualized lesions, 18 were seen with MRAP; however; five subcentimeter lesions seen with MRAP were not seen with conventional MR imaging or CTAP. Systemic recirculation of iodinated contrast material from the bolus and from previous angiography is a potential limitation of CTAP. For both CTAP and MRAP, optimal results are expected if all images are obtained during a single breath hold, within seconds of the onset of contrast agent administration. PMID- 7865936 TI - Tracking the motion of skeletal muscle with velocity-encoded MR imaging. AB - Phase-contrast magnetic resonance velocity-encoding techniques were used to track two-dimensional movement of skeletal muscle tissue. Axial and longitudinal planes in the forearms of five healthy volunteers were imaged during cyclic flexion and extension of the fingers, and the resulting data were used to plot the trajectories of the motion of pieces of muscle tissue. A phantom that produced complex two-dimensional trajectories validated the accuracy of the imaging and analysis techniques; after adjustments for phase errors, two-dimensional trajectories were tracked with an root-mean-square error of 0.1 cm. Preliminary results indicate that velocity-encoded image data can characterize motion trajectories and that refinements in data acquisition and analysis techniques may make it possible to correlate the movements of different regions within a muscle, characterize muscle contraction, and quantify longitudinal strain. This ability to track velocity vectors may provide a foundation for quantitative analysis of muscle motion. PMID- 7865937 TI - MR evaluation of cervical cancer in hysterectomy specimens: correlation of quantitative T2 measurement and histology. AB - Specimens from modified radical hysterectomies performed for invasive carcinoma of the cervix were analyzed with quantitative T2 magnetic resonance (MR) imaging and histologic study to determine to what degree there was a correlation between the findings of the two modalities. The mean T2 of cervical stroma was 48 msec, while the outer zone of the cervix had a mean T2 of 62 msec and the central canal region typically had T2 values of 115 msec +/- 20 (standard deviation). A total of nine cervical cancers were analyzed, and their mean T2 value was 79 msec. Separation between cervical stroma and tumor was good, with stromal T2 values ranging from 30 to 66 msec, while tumor T2s ranged from 60 to 97 msec. Statistical analysis indicated that these data were associated with a sensitivity of 89% and a specificity of 95%, with 95% confidence intervals of [50%, 99.4%] and [74%, 99.7%], respectively, for separating tumor from stroma on the basis of T2 value. Quantitative T2 imaging was found to provide an effective, nonsubjective means of classifying cervical anatomy and neoplastic disease. PMID- 7865938 TI - Determination of background gradients with diffusion MR imaging. AB - A new magnetic resonance (MR) imaging technique, opposite-polarity pulsed-field gradient technique, with which the effects of background magnetic field gradients can be separated from the effects of diffusion, is described. It is based on the processing of two sets of diffusion-weighted images, the acquisition parameters of which differ only in the polarity of the applied diffusion pulses. The two effects can be separated because the cross term (bc) of the gradient factor function is antisymmetric with respect to reversal of the sign of the applied diffusion pulses. The technique permits simultaneous measurement of the spatial distribution of both the diffusion constants and background magnetic field gradients, with the same spatial resolution as the parent images from which they were derived. The technique has been validated with a phantom in which the spatial distribution of susceptibility-induced background gradients is known, the results showing excellent agreement with theory. The technique was applied to two systems in which the spatial distribution of the background gradient is unknown. Sources of error in the measurement of background gradients and (unrestricted) diffusion constants are analyzed, including the effects of voxel size, partial volumes, and interactions between background and imaging gradients. PMID- 7865939 TI - Effects of MR exposure on cell proliferation and migration of chick motoneurons. AB - The effect of magnetic resonance (MR) exposure on the proliferation and migration of motoneurons was examined in chick embryos. Embryos were exposed in ovo to a static magnetic field of 1.5 T for 6 hours and to 64-MHz radio-frequency field pulses and a switched magnetic field gradient with an amplitude of 0.6 G/cm for 4 hours. For cell proliferation studies, embryos were exposed to MR fields during the developmental stage at which motoneuron proliferation is most active. For cell migration studies, embryos were exposed to MR fields at the developmental stage just before lateral motoneuron migration. The results show that the birth dates, migration, and proliferation of lateral motoneurons were unaffected by the MR exposure conditions in this study. PMID- 7865941 TI - MR susceptometry: an external-phantom method for measuring bulk susceptibility from field-echo phase reconstruction maps. AB - A novel method for estimating the susceptibility of an object by using the magnetic resonance (MR) imaging field distortions in an external-reference water bath next to the object is described. The field measurement was obtained with a phase reconstruction from a gradient-echo acquisition. A field model of an arbitrary object in a static magnetic field was discretely calculated from geometry determined from the magnitude reconstruction. Least-squares estimation yields the susceptibility of the object. Required (and proven) assumptions include validity of superposition, object homogeneity, negligible higher-order field terms, field-model accuracy, geometric-model accuracy, and correlation of gradient-echo phase to field distortion. MR susceptometry estimation of phantoms yielded susceptibility estimates that correlated well with known values (r > .9975). This MR susceptometry method is a first step toward quantitation of iron levels through MR imaging phase information in patients with iron overload. PMID- 7865940 TI - Effect on fetal mouse development of exposure to MR imaging and gadopentetate dimeglumine. AB - Pregnant mice were exposed to one of five regimens at 9.5 days of gestation: no treatment (group 1), intraperitoneal injection of normal saline (group 2), intraperitoneal injection of gadopentetate dimeglumine (group 3), intraperitoneal injection of gadopentetate dimeglumine and magnetic resonance (MR) exposure (group 4), and MR exposure alone (group 5). At 18 days of gestation, the mice were sacrificed and fetuses were removed and examined for the following end points: litter size, number alive or dead, fetal weight, extremity morphology, eye and ear development, and appearance of the head. A total of 739 fetuses were analyzed: group 1 (n = 161), group 2 (n = 149), group 3 (n = 142), group 4 (n = 136), and group 5 (n = 151). The only statistically significant difference was a lower mean fetal weight in the saline-injection group compared with the control group. The results show that MR exposure with and without gadopentetate dimeglumine had no adverse effect on the end points analyzed. PMID- 7865942 TI - Effect of joint position and ligament tension on the MR signal intensity of the cruciate ligaments of the knee. AB - Six cadaveric lower extremities were imaged with T1-weighted spin-echo pulse sequences with the knees extended and flexed to 90 degrees. Magnetic resonance signal intensities of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) were compared. Changing from extension to flexion resulted in decreased signal intensity in six of six ACLs and five of six PCLs. Two of the knees were then imaged with and without tension applied to the ACL. Both specimens showed a decrease in signal intensity with tension, followed by an increase in signal intensity with release of the tension. Finally, in three of the limbs the ACL was surgically reconstructed and then imaged with and without tension applied to the tendon graft. Signal intensity decreased with tension and increased with release of the tension in all three specimens. Thus, joint position and changes in ligament tension affect the signal intensity of the ACL and PCL, generally resulting in a signal intensity decrease with tension. PMID- 7865943 TI - Eddy current correction in volume-localized MR spectroscopy. AB - The quality of volume-localized magnetic resonance spectroscopy is affected by eddy currents caused by gradient switching. Eddy currents can be reduced with improved gradient systems; however, it has been suggested that the distortion due to eddy currents can be compensated for during postprocessing with a single frequency reference signal. The authors propose modifying current techniques for acquiring the single-frequency reference signal by using relaxation weighting to reduce interference from components that cannot be eliminated by digital filtering alone. Additional sequences with T1 or T2 weighting for reference signal acquisition are shown to have the same eddy current characteristics as the original signal without relaxation weighting. The authors also studied a new eddy current correction method that does not require a single-frequency reference signal. This method uses two free induction decays (FIDs) collected from the same volume with two sequences with opposite gradients. Phase errors caused by eddy currents are opposite in these two FIDs and can be canceled completely by combining the FIDs. These methods were tested in a phantom. Eddy current distortions were corrected, allowing quantitative measurement of structures such as the -CH = CH- component, which is otherwise undetectable. PMID- 7865944 TI - MR measurements of pulsatile pressure gradients. AB - A magnetic resonance (MR) imaging method for evaluating pulsatile pressure gradients in laminar blood flow is presented. The technique is based on an evaluation of fluid shear and inertial forces from cardiac-gated phase-contrast velocity measurements. The technique was experimentally validated by comparing MR and manometer pressure gradient measurements performed in a pulsatile flow phantom. Analyses of random noise propagation and sampling error were performed to determine the precision and accuracy of the method. The results indicate that a precision of 0.01-0.03 mmHg/cm and an accuracy of better than 8% can be achieved by using standard clinical pulse sequences in tubes exceeding 6 mm in diameter. The authors conclude that MR measurement of pressure gradients is feasible and that additional hemodynamic information may be derived from conventional phase-contrast imaging studies. PMID- 7865945 TI - Diffusion imaging with the MP-RAGE sequence. AB - Diffusion-weighted magnetic resonance (MR) images obtained with conventional spin echo techniques are known to be sensitive to subject motion because of long image acquisition times. To reduce the acquisition time, use of a magnetization prepared rapid gradient-echo (MP-RAGE) sequence modified for diffusion sensitivity was studied. In this sequence, a preparation phase with a 90 degrees 180 degrees-90 degrees pulse train is used to sensitize the magnetization to diffusion. Centric-ordered phase encoding, short TRs (5.2-6.5 msec), and small flip angles (5 degrees-8 degrees) are necessary to minimize saturation effects from tissues with short relaxation times. Phantom studies with various concentrations of copper sulfate (T1 ranging from 2,459 to 90 msec) were performed to validate that the diffusion-weighted signal obtained with the MP RAGE sequence was independent of relaxation time. Diffusion-weighted images of water, isopropyl alcohol, and acetone were acquired to confirm the accuracy of measured diffusion coefficients. Brain images of healthy normal volunteers were obtained to demonstrate motion insensitivity and general image quality of the technique. The results indicate that accurate diffusion-weighted images can be obtained with a diffusion-weighted MP-RAGE sequence, with imaging times of about 1 second. PMID- 7865946 TI - Dynamic spin-echo imaging: theoretical assessment and implementation. AB - A spin-echo method for obtaining dynamic magnetic resonance (MR) images is described. The method combines the RARE (rapid acquisition with relaxation enhancement) pulse sequence with a data acquisition scheme in which only a centric fraction of the raw data is sampled to increase the time resolution of the dynamic images. The missing high-resolution data are supplied from reference images. By these means, an effective time resolution of about 10 seconds per image is achieved, which is suitable for diagnostic assessment of contrast enhancement procedures. A promising clinical application is contrast-enhanced MR imaging of the pituitary. Although the resolution of small objects in this size range is potentially degraded, this shortcoming is compensated for with use of variable refocusing flip angles. In the context of pituitary imaging, the centric 30%-40% of the raw data is shown to be the optimal fraction to acquire for the low-resolution dynamic images. Ten patients with previous history of pituitary disease have been imaged with dynamic and conventional spin-echo techniques. In six of these patients, an equivalent diagnosis was reached with dynamic and conventional images, while in two, only the dynamic images showed the lesion; in the final two patients, only the conventional images showed the lesion. PMID- 7865948 TI - Silicone-fat differentiation in the breast: exploiting the bright-fat phenomenon in fast spin-echo MR imaging. AB - Selective suppression of silicone or fat with chemical shift-selective (CHESS) pulses is difficult because of the small chemical shift difference between the primary lipid signal and the primary silicone signal at 1.5 T. Differentiation of these chemically distinct species is, however, an important clinical task in assessing implant rupture and silicone migration in breast tissue. A method uniquely suited for silicone-fat differentiation with fast spin-echo (FSE) sequences is reported. It is based on the dependence of fat signal on echo spacing in FSE imaging and results show that it may provide a clinically robust method for silicone-fat differentiation in magnetic resonance imaging of the breast. PMID- 7865947 TI - Effects of physiologic waveform variability in triggered MR imaging: theoretical analysis. AB - One of the assumptions inherent in most forms of triggered magnetic resonance (MR) imaging is that the pulsatile waveform (be it cardiac, respiratory, or some other) is purely periodic. In reality, the periodicity condition is rarely met. Physiologic waveform variability may lead to image artifacts and errors in velocity or volume flow rate estimates. The authors analyze the effects of physiologic waveform variability in triggered MR imaging. They propose that this variability be treated as a modulation of the underlying motion waveform. This report concentrates on amplitude modulation of the velocity waveform, which results in amplitude and phase modulation of the transverse magnetization. Established Fourier and modulation theory and the recently described principles of (k,t)-space were used to derive the appearance of physiologic waveform variability artifacts in triggered MR images and to predict errors in time averaged and instantaneous velocity estimates that may result from such motion effects, including effects such as ghost overlap. Simulations and experimental results are provided to confirm the theory. PMID- 7865949 TI - Safety and optimum concentration of a manganese chloride-based oral MR contrast agent. AB - To determine the safety of a manganese chloride-based oral magnetic resonance (MR) contrast agent and the ideal concentration of the agent for marking in three different anatomic sites (stomach, middle of the small bowel, and ileocecal region), six healthy volunteers were evaluated before and after administration of 900 mL of three different concentrations of the contrast agent. Images were evaluated subjectively and objectively. No adverse events were noted. There was a minimal rise in manganese blood levels at 6 hours after administration, with a return to baseline at 24 hours. The imaging data demonstrated good-to-excellent bowel marking on T1-weighted images at all three concentrations. However, on T2 weighted images, the 40 mg Mn+2/L concentration provided improved hypointense bowel marking relative to the 20 mg/L concentration. Little difference was seen between the 40 and 60 mg/L concentrations. Fast T1- and T2-weighted sequences provided superior image quality to that of conventional spin-echo sequences. PMID- 7865950 TI - Registration of images from sequential MR studies of the brain. AB - For sequential studies of patients with brain tumors, the authors have designed an automated registration procedure for intra- and interexamination alignment of magnetic resonance images. This was evaluated with artificially misregistered data and data from repeat studies of six healthy volunteers and six brain tumor patients. In a subset of cases, a manual procedure based on matching of neuroanatomic landmarks was also applied for comparison. The results showed that the technique is robust and reproducible, giving an accuracy in the range of 1-2 mm, which corresponded to the spatial resolution of the images. Subject motion between imaging sequences within the same study was negligible, although adjustments (one to two section thicknesses) were required in the z direction to correlate multisection and volume images and to allow accurate image segmentation. For alignment between sequential volunteer and patient examinations, translations of up to 22 mm and rotations in the x, y, and z axes of up to 9 degrees were required. This alignment procedure may be valuable in numerous aspects of treatment planning and patient follow-up. PMID- 7865951 TI - Conservation surgery for breast cancer: selection criteria and technical considerations. AB - Patients with stage I or II breast cancer are candidates for either modified radical mastectomy or breast preservation therapy involving limited resection of the primary tumor, axillary dissection, and breast irradiation. The overall survival rates of both these approaches are comparable according to retrospective reviews and ongoing clinical trials, and long-term follow-up confirms the earlier findings. Thus, patients should be given the choice between these two options by surgeons, radiation therapists, and other physicians involved in their care. However, not all breast cancer patients will choose breast preservation surgery, and because of tumor-related and other factors not all patients are candidates. The patient selection criteria are discussed herein and the optimal surgical techniques are reviewed. PMID- 7865952 TI - Gastrointestinal hormones and cell proliferation. AB - There is no question that gut peptides are trophic for normal gut mucosa. Gut peptides can function in an endocrine, paracrine or autocrine fashion. We examined the effects of gut peptides on the growth of animal and human cancers of the gastrointestinal (GI) tract and pancreas in vivo and in vitro. We also examined the role of growth factors and bioamines in the regulation of growth of human endocrine tumors. Our studies have shown that gut peptides (gastrin, VIP, neurotensin, and bombesin) regulate growth of some cancers of the GI tract and pancreas. We have found that peptide action is mediated through specific receptors and that cell-specific differences in receptor expression occur. We have also begun to examine the intracellular signal-transduction pathways involved in endocrine and autocrine actions of these peptides on growth of GI cancers. We have found that cell-type-specific differences exist among the various signal-transduction pathways (cyclic AMP, phosphatidylinositol hydrolysis (PI), intracellular calcium ([Ca2+]i) mobilization, and tyrosine phosphorylation) and that different receptors for the same hormone may be linked to different signal-transduction pathways depending upon cell type. We have also found that autocrine growth regulation of human pancreatic carcinoid occurs through specific receptor-mediated signal-transduction pathways. We will discuss the mechanisms of action and potential therapeutic uses of manipulation of gut hormone levels or hormone antagonists to inhibit the growth of GI tract cancers. PMID- 7865953 TI - Initiation of a fibrinolytic system in hepatic resection: the roles of tissue type plasminogen activator and plasminogen activator inhibitor-1. AB - The factors related to the initiation of fibrinolysis, especially with regard to the tissue-type plasminogen activator (tPA) and the plasminogen activator inhibitor-1 (PAI-1), were investigated in 15 patients who underwent hepatic resection, and the findings were compared between those with normal livers and those with diseased livers. It was found that tPA increased before hepatic division, whereas PAI-1 increased after hepatic division and reached a peak immediately following the operation. Plasminogen decreased during hepatectomy, reaching its lowest point on postoperative day 1, and increasing later. Decreased levels of both plasminogen and the alpha 2-plasmin inhibitor were considered to be partly due to plasmin formation in the blood. Patients with a diseased liver tended to have higher intraoperative values of euglobulin lysis activity and higher postoperative values of plasminogen activator, but significantly lower postoperative values of alpha 2-plasmin inhibitor than those with a normal liver. The results of this study suggest that activation of the fibrinolytic system occurs both during hepatectomy and in the early postoperative period, and that patients with a diseased liver are prone to develop hyperfibrinolysis during hepatectomy. Moreover, the increased levels of both tPA and PAI-1 can serve as one of the most sensitive markers for the vital reaction against surgical stress. PMID- 7865954 TI - The effects of massive transfusion and haptoglobin therapy on hemolysis in trauma patients. AB - A retrospective study was conducted on 53 patients who suffered severe trauma to determine the severity of intravascular hemolysis, the variations of renal function after trauma, and the effects of transfusion and haptoglobin therapy on these factors. Serum total haptoglobin, total hemoglobin, and urine free hemoglobin were measured 0, 1, 3, and 5 days after the trauma and renal tubular function was evaluated by the urinary N-acetyl-beta-D-glucosaminidase (NAG) index. Patients were divided into two groups depending on whether or not haptoglobin was given: group A (n = 34) did not receive haptoglobin, and group B (n = 19) was administered 4,421 +/- 245 U haptoglobin based on clinical indications. The total transfusion volumes were 3,477 +/- 594 ml and 10,146 +/- 1,794 ml, in groups A and B, respectively (P < 0.01). In group A, total haptoglobin was remarkably decreased to 69.4 +/- 11.6 mg/dl on day 0, but recovered to within the normal range on day 3, while the total hemoglobin was increased and the urine hemoglobin was positive in 61.8% of the patients. In group B, decreases in total haptoglobin and increases in total hemoglobin were more remarkable, and 84.2% had a positive urine hemoglobin. On day 5, groups A and B had NAG indices of 18.8 +/- 3.3 and 133.6 +/- 33.8 U/L/creatinine respectively (P < 0.01). These findings led us to conclude that trauma caused hemolysis and that the administration of 4,000 U haptoglobin did not improve either the severity of hemolysis or the deteriorated renal tubular function caused by massive transfusion. PMID- 7865955 TI - Abdominal sonography for the diagnosis of large bowel obstruction. AB - To evaluate the clinical usefulness of abdominal sonography in the diagnosis of large bowel obstruction, the sonographic findings of 39 patients with a large bowel obstruction, in the form of a simple obstruction in 36 patients and a sigmoid volvulus in 3, were reviewed in comparison with their plain X-ray findings. Abdominal sonography showed a large bowel obstruction in 33 patients, and an obstructing lesion in 14 of these patients. However, in the other 6 patients, including the 3 with a sigmoid volvulus, the image was disturbed by extensive colonic gas. Although the plain abdominal X-ray films showed no gaseous colonic dilatation, isolated small bowel dilatation was seen in six patients with a large bowel obstruction proximal to the splenic flexure. In five of these six patients, abdominal sonography revealed a dilated colon filled with fluid and feculent contents which was difficult to evaluate on the plain X-ray films. Consequently, abdominal sonography was proven to be useful, especially for detecting X-ray-negative colonic dilatation. PMID- 7865956 TI - Reappraisal of internal mammary lymph node dissection in selected patients with invasive breast cancer. AB - We performed a new type of en bloc extended radical mastectomy (EXT) as a clinical trial in 118 patients from 1980 through 1985. A variety of conventional radical mastectomies (RDL) were also undertaken in 105 patients from 1973 through 1985. In this retrospective study, univariate and multivariate analyses were performed to compare the results of EXT and RDL. The univariate analysis showed that the 10-year survival rates for the EXT and the RDL groups were 86% +/- 3.3% and 77% +/- 4.2%, respectively (P = 0.073 with the Cox-Mantel test). For the subgroups stratified according to the status of axillary lymph node involvement, the EXT was significantly better in patients with one to three metastatic axillary lymph nodes (P = 0.016). The adjusted Cox regression analysis revealed that the favorable results of EXT were most encouraging in the patients with one to three metastatic axillary lymph nodes (P = 0.058). Therefore, it is suggested that an EXT may be more advantageous than RDL in selected patients with resectable invasive breast cancer. PMID- 7865957 TI - The effects of a temperature below 15 degrees C on the myocardial calcium and ultrastructure in donor heart preservation in a canine model. AB - The effects of 6-h hypothermic cardioplegic arrest on myocardial biochemical, morphologic, and functional recovery were investigated in two groups of dogs. Group 1 (n = 6) was subjected to hypothermia of 15 degrees C and group 2 (n = 6) was subjected hypothermia of 5 degrees C. Although the myocardial calcium (Ca) concentration was significantly higher at the end of reperfusion in group 2 compared to group 1, the MB-fraction of creatine kinase, mitochondrial aspartate aminotransferase, recovery of left ventricular systolic function, and mitochondrial morphologic integrity were better in group 2 than in group 1. These findings suggest that hypothermia of 5 degrees C in 6-h cardioplegia is not necessarily coupled with interference in myocardial contractility, despite the Ca overload that occurs during reperfusion. PMID- 7865958 TI - Non-Hodgkin's lymphoma of the gastric stump developing 9 years after a distal gastrectomy for a peptic ulcer: a case report and review of the literature. AB - We report herein the case of a 65-year-old man who developed non-Hodgkin's lymphoma of the gastric stump 9 years after undergoing a distal gastrectomy for a gastric ulcer. The patient presented with epigastric discomfort, and an upper gastrointestinal series and gastroscopy revealed a lymphoma lesion located close to the site of his gastroduodenal anastomosis. A total gastrectomy was performed, followed by combination chemotherapy, comprised of vincristine, Endoxan, prednisone and Adriamycin (VEPA). Histologically, the resected specimen was diagnosed as non-Hodgkin's lymphoma. The patient has remained well without any signs of recurrence for 18 months since his operation. Although there have been a number of reports of adenocarcinoma developing in the gastric stump following surgery for peptic ulcers, the development of malignant lymphoma under such conditions is rare. Following the presentation of this case, we review the available literature and discuss the possibility of malignant lymphoma developing in the gastric stump. PMID- 7865959 TI - Rapidly deteriorated failure of Carpentier-Edwards porcine bioprosthesis caused by three detached commissures: report of a case. AB - A 58-year-old man required an emergency redo mitral valve replacement due to a rapidly deteriorating failure of the Carpentier-Edwards porcine bioprosthesis within [corrected] a few days after the initial operation. The removed bioprosthesis showed that its three commissures had all peeled off each stent, which may have occurred within a short time, and caused massive, rapidly progressive trans-bioprosthetic regurgitation. PMID- 7865960 TI - A solid and cystic tumor of the pancreas in a 10-year-old girl: report of a case and review of the literature. AB - We report herein the unusual case of a 10-year-old girl in whom a neoplasm developed in the head of the pancreas. Complete extirpation of the tumor was performed, which was histologically classified as a "solid and cystic tumor of the pancreas." Postoperative DNA analysis revealed a diploid pattern. The patient remains well with no sign of tumor recurrence 2 years after her operation. Thus, complete tumor extirpation without pancreatectomy is recommended for pediatric patients when there is no direct invasion to the adjacent organs or distant tumor metastasis. PMID- 7865961 TI - Foreign-body granuloma mimicking an extrahepatically growing liver tumor: report of a case. AB - We herein describe a 74-year-old woman with a foreign-body granuloma mimicking a liver tumor. Imaging studies revealed a pedunculated left lobe mass in the setting of chronic liver disease. She had a past history of a cholecystectomy as well as a previous gynecological operation. A left lateral segmentectomy was performed because of the possibility of a rupture. The dissected specimen showed a foreign-body granuloma caused by gauze. We believe this case to be a very unique granuloma, which should be kept in mind whenever making a diagnosis of a liver tumor particularly in a patient with chronic liver disease, who has a past history of abdominal surgery. PMID- 7865962 TI - A cavernous hemangioma of the rectum treated as a hemorrhoid for 1 year prior to its diagnosis: report of a case. AB - We report herein the case of a 28-year-old woman with a rectal cavernous hemangioma in whom recurrent rectal bleeding and marked anemia were interpreted as being caused by her coexisting internal hemorrhoids, resulting in a delay in the correct diagnosis for 1 year. Digital examination revealed a walnut-sized, wide-based, and elastic soft mass, 3 cm proximal from the anal verge, in addition to the internal hemorrhoids. Colonofiberscopy revealed a bluish submucosal lesion with superficial capillary dilatation at the same site. A transanal local resection was performed and the histological diagnosis of the tumor was cavernous hemangioma. The patient has been well without any recurrence of rectal bleeding for 2 years and 6 months since her operation. Thus, although rectal cavernous hemangioma is rare, a lack of awareness of this condition could lead to misdiagnosis as hemorrhoids and subsequent inappropriate therapy. PMID- 7865963 TI - Spontaneous rupture of the descending aorta through atherosclerotic plaque: report of a case. AB - Spontaneous rupture of the thoracic descending aorta is rare, and uniformly fatal without surgery. We report herein the case of a man in whom such a rupture was successfully treated with emergency surgery. We believe that the rupture in this patient was most likely associated with perforation through an atherosclerotic plaque of the descending aorta and was induced by sudden hypertension. PMID- 7865964 TI - Cavernous transformation of the portal vein coinciding with early gastric cancer and cholelithiasis. AB - A 71-year-old man who developed jaundice with a high-grade fever was admitted to our hospital. The episode was ascribed to cholecysto-choledocholithiasis. In the preoperative evaluation, a cavernous transformation of the portal vein and an early gastric cancer were found. The patient thereafter underwent an operation for those pathologies after the endoscopic removal of a choledochal stone; cholecystectomy, and a distal gastrectomy with regional lymph node dissection for gastric cancer. The proposed procedures of gastrectomy and cholecystectomy were completed without any major difficulty because no markedly enlarged collateral veins were found in the area where the regional lymph node dissection was carried out. Thanks to advances in imaging modalities, an asymptomatic cavernous transformation of the portal vein coinciding with gastric cancer such as that seen in the present case may be increasingly encountered in the future. The greatest caution, however, needs to be exerted at operation to minimize any unexpected bleeding and to avoid any interruption of the porto-portal shunts in such cases. Further, the reestablishment of the portal blood supply to the liver might be required in advanced cases of gastric cancer, where regional lymph node dissection may necessitate skeletonization of the hepatoduodenal ligament for curative purposes. PMID- 7865965 TI - Resection of metastatic thyroid carcinomas to the liver and the kidney: report of a case. AB - Differentiated thyroid cancer is considered to have a quite favorable prognosis. However, some patients die as a result of distant metastasis, which mainly consists of pulmonary, mediastinal, or osteal metastases. The biological features of the tumor, such as a slow growth gradient, indicate the possibility of achieving comparatively satisfactory results in the treatment of such distant metastases. A complete surgical excision of the distant metastases in differentiated thyroid carcinoma has been reported to offer the best chance for prolonged survival. A case of unusual metastasis sites on the caudate lobe of the liver and right kidney occurring in a 72-year-old woman is herein presented. The location of the surgically treated distant metastases of the papillary thyroid carcinoma make this case unique. PMID- 7865966 TI - The distribution of secretory immunoglobulin A in the intrahepatic biliary epithelium of patients with hepatolithiasis. AB - In the treatment of hepatolithiasis, liver resection helps to prevent recurrence and may reduce the incidence of infection by removal of the atrophic tissue. This study was conducted to determine if the affected liver tissue in hepatolithiasis is inflamed or has lowered local immunity by examining the distribution of secretory immunoglobulin A (sIgA) and proliferating cell nuclear antigen (PCNA) in the intrahepatic biliary tracts of 27 patients with hepatolithiasis. Operative specimens were sectioned and stained with avidinbiotin complex, and the labeling index for both sIgA and PCNA was calculated as a percentage of the biliary epithelial cells stained. Cells stained for sIgA increased to a certain point as the cholangitis became more severe; however, in advanced cholangitis, with severe parenchymal atrophy or actively proliferating biliary epithelium, there were fewer cells stained for sIgA than in mild cholangitis. In hepatolithiasis, the decreased local immunity related to sIgA accompanied severe chronic proliferative cholangitis and parenchymal atrophy. PMID- 7865967 TI - Tubed latissimus dorsi musculocutaneous flaps for thoracic esophageal replacement in dogs: possible clinical application. AB - A circumferential defect of the intrathoracic esophagus was successfully replaced with a tubed latissimus dorsi musculocutaneous flap in dogs. This flap obviates the necessity for laparotomy. Therefore, this technique might offer an alternative means of esophageal reconstruction in debilitated patients. PMID- 7865968 TI - AHNA certificate program in holistic nursing courses. AHNA certificate program in healing touch courses. PMID- 7865969 TI - Independent practice. PMID- 7865970 TI - I never thought I'd do it. PMID- 7865971 TI - A Kenyan experience. PMID- 7865972 TI - It's all a healing journey. PMID- 7865973 TI - Tell Jeannie I love her. PMID- 7865974 TI - Hibernating, stunning and ischemic preconditioning of the myocardium: therapeutic implications. AB - Hibernating myocardium, as a compensatory mechanism to chronic ischemia caused by a tight coronary stenosis is best treated by restoration of blood flow. Hence in this condition the therapeutic implications are rather obvious and the problem is how to diagnose hibernating myocardium. Provocation tests and/or scintigraphic methods are usually used to show viability of an akinetic myocardial area. These tests, however, can be expected to be clearly positive only if hibernating myocardium is not mixed with patchy scar tissue. Physicians should be aware of myocardial stunning, when left ventricular function remains impaired immediately after revascularization, for example, after cardiac surgery of the totally ischemic organ or after thrombolytic therapy of acute myocardial infarction. Due to the self-recovery of this condition, therapeutic implications are given only when symptoms and signs of impaired ventricular function are present. Positive inotropic agents have been shown to be effective in experimental conditions and are widely accepted to be beneficial in clinical use. Based on experimental observations the term "ischemic preconditioning" has been introduced to describe a condition of increased ischemic tolerance after a short preceding period of ischemia and reperfusion. This condition, however, has never been proven to be of clinical significance in the treatment of patients with ischemic heart disease. According to some clinical observations, repeated episodes of ischemia are even associated with a worse prognosis. Therapeutic implications may arise from understanding the mechanisms involved in this cardioprotective process, for example, activation of adenosine A1 receptors. PMID- 7865975 TI - Molecular therapeutic strategies in hepatitis B virus infection. AB - Chronic infection with the hepatitis B virus is a major health problem worldwide. The only established therapy is interferon-alpha, with an efficacy of only 30-40% in highly selected patients. Nucleoside analogues do not show a significant clinical benefit. Molecular therapeutic strategies aimed at blocking gene expression include antisense DNA/RNA and ribozymes acting at the posttranscriptional level and triple helix formation blocking at the transcriptional level. In vitro, antisense oligodeoxynucleotides inhibit viral replication and gene expression in human hepatoma cell lines. In vivo, an antisense oligodeoxynucleotide directed against the 5'-region of the pre-S gene of the duck hepatitis B virus inhibited viral replication and gene expression in ducks. In vitro, ribozymes accurately cleave HBV substrate RNA. Triple helix formation is another very promising molecular approach. Results in hepadnaviral infection are not yet available, however. PMID- 7865976 TI - Colonic fermentation: metabolic and clinical implications. AB - Colonic SCFA formation from fermentable carbohydrate is important for the maintenance of morphologic and functional integrity of the colonic epithelium. Carbohydrate-induced diarrhea occurs when the amount of carbohydrate entering the colon exceeds its fermentation capacity. Deficient availability or utilization of SCFA, mainly of n-butyrate, is the cause of diversion colitis and may play important roles in colonic carcinogenesis, in starvation and enterotoxigenic diarrhea, and in idiopathic UC. PMID- 7865977 TI - Lupus therapy. PMID- 7865978 TI - Impact of long-term hemodialysis on nutritional status in patients with end-stage renal failure. AB - We evaluated the way in which duration of hemodialysis treatment affects nutritional status in 96 end-stage renal failure patients. According to the length of previous hemodialysis treatment patients were divided into the groups: onset hemodialysis (ON-HD), early-stage hemodialysis (ES-HD, 1-8 months), mid stage hemodialysis (MS-HD, 9-69 months), and advanced-stage hemodialysis (AS-HD, 70-207 months). Nutritional status was assessed by laboratory data (serum proteins, total lymphocyte count), intradermal skin antigen testing, anthropometric measurements (body mass index [BMI], infrared interactance), and records of food intake. ON-HD patients on a low-protein diet exhibited abnormally low values for serum total protein, albumin, transferrin, and total lymphocyte count and a high prevalence of anergy to skin antigens (69%). In the ES-HD and MS HD groups values for serum proteins and total lymphocyte count were in the normal range and significantly higher than in ON-HD patients. In addition, a lower proportion of cutaneous anergy was observed (50% and 27%, respectively). Long term hemodialysis therapy for 6-17 years (AS-HD) was associated with normal levels for all measured serum proteins. Subnormal levels of total lymphocyte count, significantly lower than in MS-HD patients, were associated with an increase in anergy to skin antigens (46%). Serum prealbumin, complement C3c, BMI, body fat, and lean body mass exhibited normal values in all patients and showed no differences between groups. These results indicate that diminished visceral protein stores, lymphopenia, and anergy to skin antigens are widespread in undialyzed uremic patients with end-stage renal failure but become uncommon after the initiation of regular hemodialysis therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865979 TI - Indomethacin treatment in amphotericin B induced nephrogenic diabetes insipidus. AB - Nephrogenic diabetes insipidus (NDI) is a serious side effect of various drugs. Elevated renal prostaglandin E2 levels have been found in patients with lithium induced NDI and have been implicated in the pathogenesis. We report the case of a patient who developed NDI following treatment with amphotericin B. Prostaglandin levels were elevated. Indomethacin had an antidiuretic effect and normalized prostaglandin levels. PMID- 7865980 TI - Localization of the bronchodilator effect induced by type A natriuretic peptide in asthmatic subjects. AB - Type A natriuretic peptide (CDD/ANP-99-126) in its circulating form was analyzed with respect to the localization of its bronchodilating effects in asthmatic subjects in vivo. The intravenous infusion of 5.7, 11.4, and 17.1 pmol kg-1 min-1 CDD/ANP-99-126 caused a significant bronchodilation of both central and peripheral airways. While the localization of the bronchodilating effects was similar to beta 2-agonists, an improvement in lung function parameters comparable to these substances was not observed. But other members of the natriuretic peptide family may reveal a stronger bronchodilating potency. PMID- 7865981 TI - Carotid artery stenosis and tachyarrhythmias: regional cerebral blood flow during high-rate ventricular pacing after one vessel occlusion in rats. AB - The aim of the present study was to investigate the effect of hypotensive tachycardias on cerebral blood flow (CBF) in the presence of significant carotid stenosis. The experiments were performed in 57 spontaneously breathing rats during arterial normoxia and normocapnia anesthetized with thiobarbital. CBF was determined with radiolabeled microspheres during control conditions (normofrequent sinus rhythm, normotension; group A; n = 15), during high-rate left ventricular pacing (660-840 ppm) at normotension (group B1; n = 13), borderline hypotension (group B2; n = 15) and severe hypotension (group B3; n = 7). In addition, CBF measurements were performed during borderline hypotension induced by hemorrhage (group C; n = 7). Global CBF was 1.09 +/- 0.29 ml g-1 min-1 in group A, 0.93 +/- 0.40 in group B1, 0.68 +/- 0.31 in group B2 (P < 0.05 vs. A), 0.42 +/- 0.16 in group B3 (P < 0.05 vs. A) and 0.83 +/- 0.2 in group C. The highest CBF values were found in the cerebellum (A; 1.43 +/- 0.5 ml g-1 min-1) and the lowest in the postocclusive tissue of the ipsilateral hemisphere (A; 0.74 +/- 0.2 ml g-1 min-1). In all groups a 15% mean CBF reduction in the right hemispherical cerebrum in comparison to the left hemisphere was observed (P < 0.01). In contrast, hemispherical CBF of the cerebellum did not differ. The CBF blood pressure relationship shifted to lower CBF values, the threshold of CBF regulation shifted to higher blood pressure values in the tissue regions distal to the occluded vessel during hypotensive tachycardias.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7865982 TI - Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome. The Phospholipase A2 Study Group. AB - There is increasing evidence that the hypercortisolemia in inflammatory diseases suppresses the elaboration of proinflammatory cytokines, thus protecting the host from its own defence reactions. In severe sepsis and septic shock cortisol levels are usually elevated, but some patients may have relative adrenal insufficiency. This may contribute to the overwhelming systemic inflammatory response syndrome. We evaluated the impact of low-dose hydrocortisone infusion (10 mg/h) on the course of the systemic inflammatory response syndrome. This dose corresponds to a maximum secretory rate of cortisol achieved in corticotropin-stimulated healthy humans. In a prospective observational study 57 surgical patients with severe sepsis or septic shock were studied, of which in addition to the conventional treatment 12 patients were infused with low-dose hydrocortisone, and 45 were treated without any corticosteroid. In the longitudinal analysis the systemic inflammatory response--as judged by body temperature, cardiovascular response, and kinetics of inflammatory mediators such as phospholipase A2, C-reactive protein, and neutrophil elastase--started to differ in favor of the hydrocortisone-treated patients after 2 days of treatment (P < 0.05, Mann-Whitney U test). The difference disappeared after withdrawal of exogenous cortisol. Shock reversal was achieved in all patients treated with low-dose hydrocortisone. The data provide evidence that low-dose hydrocortisone infusion attenuates the systemic inflammatory response in human septic shock. From an immunological point of view a relative cortisol deficiency may contribute to the amplified immune response in systemic inflammatory diseases. A randomized clinical trial must clarify the impact of low-dose hydrocortisone infusion on the clinical course and outcome of septic shock patients. PMID- 7865983 TI - Evidence for autoimmune mechanisms in the evolution of invasive fibrous thyroiditis (Riedel's struma). AB - The etiology of Riedel's invasive fibrous thyroiditis, a rare disorder confused in the past with the more common fibrous variant of Hashimoto's disease, has remained obscure. However, the presence of mononuclear cells in the fibrosclerotic process and the detection of autoantibodies directed against thyroid-specific antigens in a large proportion of patients with invasive fibrous thyroiditis favor an autoimmune pathogenesis of invasive fibrous thyroiditis. Further, an association between invasive fibrous thyroiditis and Hashimoto's thyroiditis has been suggested. Here we report the first two patients in whom invasive fibrous thyroiditis evolved from antecedent Graves' disease, documented by the presence of thyroid dysfunction, bilateral ophthalmopathy, and thyrotropin receptor stimulating autoantibodies. The diagnosis of invasive fibrous thyroiditis was established in both instances on the basis of the established histopathological criteria. The presence of extensive mononuclear cell infiltration within the invasive fibrosclerotic process in these two patients, the close relationship between thyroid-specific autoantibodies, inflammatory parameters, and disease activity, and the response to glucocorticoid therapy all suggest the existence of a link between Graves' disease and invasive fibrous thyroiditis. These findings support the notion of autoimmune mechanisms playing a role in the pathogenesis of Riedel's invasive fibrous thyroiditis. PMID- 7865984 TI - Amanita poisoning during the second trimester of pregnancy. A case report and a review of the literature. AB - Amanita phalloides-type mushroom poisoning is well recognized as causing acute liver injury and often death. Less is known, however, of whether maternal Amanita poisoning is associated with fetal damage or not. In August 1991 four members of a family were hospitalized with food intoxication caused by Amanita phalloides and Amanita verna. One of them died from hepatic and renal failure. The survivors included a 26-year-old woman in the 23rd week of pregnancy. Her clinical symptoms and blood chemistry data (lowest prothrombin activity 23%) indicated intoxication of medium severity. The management consisted of i.v. hydration, forced diuresis, and administration of silibinin, high-dose penicillin, thioctic acid, hydrocortisone, vitamin K, and fresh frozen plasma. Sonographic and obstetric controls failed to show any fetal abnormalities in the acute phase of poisoning. In the 38th week of pregnancy she gave birth to a healthy baby, who has subsequently undergone an undisturbed development. This observation indicated that severe fetal damage did not occur in maternal Amanita poisoning in the second trimester of pregnancy. Thus, at least from the second trimester on, maternal Amanita poisoning is not necessarily an indication for induced abortion. PMID- 7865985 TI - Urinary excretion of N-acetyl-beta-glucosaminidase in slight arterial hypertension during pregnancy. PMID- 7865986 TI - International Symposium on Sodium and Hypertension. Results of randomized trials. PMID- 7865987 TI - Pituitary and adrenal hormone responses to pharmacological, physical, and psychological stimulation in habitual smokers and nonsmokers. AB - Hormone responses to injection of corticotropin-releasing hormone following bicycle ergometry and psychological stress were studied in ten habitual smokers and ten nonsmokers. Compared to injection of saline, significant increases were found in adrenocorticotropin, prolactin, growth hormone, total serum cortisol, and salivary cortisol under all three stimulations except for salivary cortisol under ergometry. Furthermore, the smokers showed significant elevations of all five hormones investigated following the smoking of two cigarettes of the subject's preferred brand. Comparisons of hormone responses between smokers and nonsmokers revealed a general trend towards stronger responses in nonsmokers. However, due to the small number of subjects investigated and considerable variation in the individual hormone responses these differences reached statistical significance only for growth hormone responses following ergometry and salivary cortisol responses after psychological stress. In addition, the circadian rhythm of salivary cortisol was measured on two occasions between 9 a.m. and 9 p.m. in the subject's natural environment. The typical circadian pattern of decreasing cortisol levels was observed, with no significant differences between smokers and nonsmokers. We conclude that chronic nicotine consumption may lead to lower responses of multiple hormones not only to nicotine but to a variety of stimuli, and that these alterations do not necessarily affect unstimulated circadian profiles of free cortisol. PMID- 7865988 TI - Treatment of acute gouty arthritis with the 5-hydroxytryptamine antagonist ondansetron. AB - We report on a 28-year-old man with hematemesis, renal dysfunction, and arterial hypertension who suffered from an acute gouty attack presenting as podagra. Because of the accompanying symptoms conventional treatment of the gouty attack with colchicine or nonsteroidal anti-inflammatory drugs was contraindicated. We treated the pain of acute arthritis with the specific 5-hydroxytryptamine subtype 3 receptor antagonist ondansetron. Within 30 min after intravenous injection of this drug a substantial degree of pain relief had occurred. Unwanted side effects due to treatment were not observed. It is suggested that the 5-hydroxytryptamine released during a gouty attack induces pain via activation of 5-hydroxytryptamine subtype 3 receptors on nociceptive afferent nerve fibers. 5-Hydroxytryptamine subtype 3 receptor antagonists may therefore be a novel class of drugs for the effective treatment of acute gouty attacks when conventional treatment is contraindicated. PMID- 7865989 TI - Metal loading and enzymatic degradation of fungal cell walls and chitin. AB - The capacity of chitin (from crab shells) and of fungal cell walls from Trichoderma harzianum to accumulate zinc, cadmium and mercury was studied as well as the effects of adsorbed metals on the enzymatic hydrolysis by Novozym 234 of the two substrates. The total adsorbing capacity with respect to these metals was estimated to be at least 10 mmol kg-1 chitin (dry weight) and 50 mmol kg-1 fungal cell walls (dry weight), respectively, at pH 6.1. Enzymatic digestion of fungal cell walls preloaded with mercury and cadmium was significantly reduced, while zinc did not cause any significant inhibition. The effect of metal complexation by chitin on the enzymatic digestion was not as pronounced as for fungal cell walls. This could reflect the fact that chitin sorbed a lower total amount of metals. The inhibitory effect of metals on the enzymatic hydrolysis was caused by the association of the metals with the two substrates and not by the presence of free metals in solution. PMID- 7865990 TI - Current aspects in metal genotoxicity. AB - While carcinogenic metal ions are mostly non-mutagenic in bacteria, different types of cellular damage have been observed in mammalian cells, which may account for their carcinogenic potential. Two modes of action seem to be predominant: the induction of oxidative DNA damage, best established for chromium compounds, and the interaction with DNA repair processes, leading to an enhancement of genotoxicity in combination with a variety of DNA damaging agents. In the case of Cd(II), Ni(II), Co(II), Pb(II) and As(III), DNA repair processes are disturbed at low, non-cytotoxic concentrations of the respective metal compounds. Even though different steps in DNA repair are affected by the diverse metals, one common mechanism might be the competition with essential metal ions. PMID- 7865991 TI - Effects on enzymes and the genetic apparatus of sheep after administration of samples from industrial emissions. AB - In the present work the influence of the administration of industrial emissions from a zinc and copper plant on aspartate aminotransferase (AST), alanine aminotransferase, gammaglutamyl transferase, creatine phosphokinase (CK), total bilirubin, serum zinc levels and the genetic apparatus was studied on seven ewes. Each animal was given a dose of 31.99 g of emissions per day. The first and the last animals died of zinc intoxication on days 42 and 58, respectively. Significantly increased zincemia could be observed from day 8 of the experiment (P < 0.01). In the enzymes under investigation, the most pronounced effects of the emission were seen in AST and CK activities. In comparison with the starting levels, AST values revealed significant differences on days 37 and 58 (P < 0.05 and P < 0.01, respectively), and CK on day 58 (P < 0.01). Significantly increased bilirubinemia (P < 0.01) could be observed from day 8 of the experiment. In the period prior to the first gavage of emission and day 30 of administration no significant increase of chromosome breaks per cell was observed in the experimental sheep. The genotoxic effect of the emission was also stated on the basis of recombination frequency visualized by means of the sister chromatid exchange test; on day 30, the increase of these disturbances revealed statistical significance (P < 0.01). PMID- 7865992 TI - Iron binding to Azotobacter salinestris melanin, iron mobilization and uptake mediated by siderophores. AB - Iron-sufficient Azotobacter salinestris cells bound large amounts of 55Fe to cell associated catechol melanin in an energy-independent manner. Iron was mobilized from the cell surface by citric acid and transported into the cell in a process that was inhibited by azide, carbonyl cyanide m-chlorophenyl-hydrazone (CCCP), KCl or RbCl, the latter two known to inhibit Na(+)-dependent activities in A. salinestris. Iron-limited cells produced a hydroxamate compound (HDX) which promoted 55Fe-uptake into iron-limited cells in a two step process. Initial uptake was inhibited by azide or CCCP, but not by KCl, while subsequent uptake was blocked by all inhibitors. Citric acid also mediated energy-dependent 55Fe uptake in iron-limited cells, but initial iron-uptake was less sensitive to CCCP than HDX-mediated iron-uptake. The results show that melanin serves as an iron trap, probably to protect the cells from oxidative damage mediated by H2O2 and the Fenton reaction. A model for HDX siderophore-mediated iron-uptake is proposed which requires energy to concentrate iron in the periplasm and H+/Na(+)-dependent events to bring iron into the cell. PMID- 7865993 TI - The interaction of gadolinium complexes with isolated rat hepatocytes. AB - The lanthanide metal, gadolinium, is currently used in contrast agents for magnetic resonance imaging. We have performed a study of the interaction between isolated rat hepatocytes and 153Gd complexed to diethylene-triamine pentaacetic acid (DTPA) or to DTPA-albumin conjugates. The study shows that isolated hepatocytes are able to take up both types of 153Gd complexes. The 153Gd-DTPA albumin complexes are apparently taken up by pinocytosis, and possibly receptor mediated endocytosis and/or adsorptive endocytosis, whereas the uptake mechanism of 153Gd-DTPA is unknown. The 153Gd-DTPA-albumin complexes, but not the 153Gd DTPA complex, are degraded by the cell. The degradation is inhibited by ammonium chloride. Gadolinium is slowly released back to the medium after loading of the cells with both complex types. In the experiments reported here no evidence of any adverse effects on the hepatocyte resulting from exposure to the 153Gd complexes were observed. PMID- 7865994 TI - The nickel resistance determinant cloned from the enterobacterium Klebsiella oxytoca: conjugational transfer, expression, regulation and DNA homologies to various nickel-resistant bacteria. AB - Klebsiella oxytoca strain CCUG 15788, isolated from a mineral oil emulsion tank in Goteborg, Sweden, was found to be nickel-resistant (tolerating 10 mM NiCl2 in non-complexing mineral-gluconate media; inducible resistance). The nickel resistance determinants were transferred by helper-assisted conjugation to various strains of Escherichia coli and Citrobacter freundii and expressed to between 5 and 10 mM NiCl2. A 4.3 kb HindIII fragment was cloned from the genomic DNA of K. oxytoca. Ligated into the vector pSUP202, the fragment caused constitutive nickel resistance (of up to 3 or 10 mM Ni2+) in various E. coli strains. After cloning into the broad host range vector pVDZ'2 the fragment even expressed low nickel resistance in the transconjugant of Alcaligenes eutrophus AE104. With the 4.3 kb HindIII fragment as a biotinylated DNA probe it was shown by DNA-DNA hybridization that the nickel resistance determinant resides on the chromosome of K. oxytoca and not on its circular plasmid pKO1 (160 kb) or linear plasmid pKO2 (50 kb). Nickel resistance strongly correlated with the presence of the 4.3 kb HindIII fragment in the transconjugants. No homologies were detected when the nickel resistance determinants of other well-known nickel-resistant bacteria, such as A. eutrophus CH34 or A. denitrificans 4a-2, were used as target DNA. Among the 60 strains examined, positive signals only appeared with the 3.1 kb DNA fragment from A. xylosoxydans 31A and the genomic DNA of two enterobacterial strains (5-1 and 5-5) isolated from nickel-rich soil in New Caledonia. PMID- 7865995 TI - Influence of a long-term zinc-deficient diet on rat platelet function and fatty acid composition. AB - A reduced zinc intake is associated with numerous abnormalities and, in particular, with hemostasis dysfunction. In this report, we studied the effects of a long-term dietary zinc restriction on platelet function. Three groups of rats were analyzed: a zinc-deficient group (ZD) and two zinc-adequate fed groups, one pair-fed (PF) and one ad libitum fed (AL). We found that ZD diet (0.2 p.p.m.) impaired ADP-induced aggregation of washed platelet after 4 and 8 weeks of diet. Thrombin-induced aggregation was impaired in ZD rats and PF rats after 8 weeks. The thrombin-induced mobilization of radiolabeled arachidonate preincorporated into platelet phospholipids was followed as well as the subsequent formation of labeled cyclooxygenase and lipoxygenase products. Stimulated platelets of ZD rats exhibited a decreased production of cyclooxygenase and lipoxygenase products, particularly after 8 weeks of diet. Moreover, platelet thromboxane generation was decreased in the ZD group as studied using a radioimmunoassay after thrombin stimulation. In addition, we measured the total fatty acid compositions of platelet and plasma. As a whole, 20:5 (n - 3) and 22:5 (n - 3) fatty acids content were significantly increased in platelet lipids after 8 weeks. On the other hand, it is known that enrichment of these fatty acids through dietary studies, both in animal and human as well as in vitro incorporation in platelets, resulted in an inhibition of platelet function. Consequently, these changes in platelet membrane fatty acid composition may contribute to the impaired platelet aggregation observed in ZD rats. PMID- 7865996 TI - Rat osseous plate alkaline phosphatase: mechanism of action of manganese ions. AB - Polidocanol-solubilized osseous plate alkaline phosphatase was modulated by manganese ions in a similar way as by zinc ions. For concentrations up to 1.0 nM, the enzyme was stimulated by manganese ions, showing site-site interactions (n = 2.2). However, larger concentrations (> 0.1 microns) were inhibitory. Manganese ions could play the role of zinc ions stimulating the enzyme synergistically in the presence of magnesium ions (Kd = 7.2 microns; V = 1005.5 U mg-1). Manganese ions could also play the role of magnesium ions, stimulating the enzyme synergistically in the presence of zinc ions (Kd = 2.2 microns; V = 1036.7 U mg 1). However, manganese ions could not substitute for zinc and magnesium at the same time since ion assymetry is necessary for full activity of the enzyme. A steady-state kinetic model for the modulation of enzyme activity by manganese ions is proposed. PMID- 7865997 TI - [Preliminary clinical study on prevention of bone loss in postmenopausal women with kidney invigoration]. AB - The effect of Bushen Migu Ye (BSMGY) on preventing the bone loss in postmenopausal women was observed. 43 healthy women with the menopause within 5 years were randomly divided into the treated and control groups, which were basically similar in age and menopausal time. BSMGY and Rhizoma Dioscoreae decoction was given orally in two groups. Some biochemical parameters related to bone metabolism, serum estradiol and forearm bone density were taken before and after treatment. The results showed that 5 months after BSMGY treatment, the ulnar and radial bone mineral content was higher than that of pretreatmental value (P < 0.05), while in control group this index was continually decreased. The change in bone density were also significant different (P < 0.05). It seems that BSMGY is able to prevent the bone loss in postmenopausal women. In the treated group, ratio of fasting urinary calcium and hydroxyproline to creatinine was lower than that of before treatment and the control group (P < 0.05); the concentration of serum alkaline phosphatase had no significant difference (P < 0.05). This preliminary study suggested that one of the therapeutic mechanism of BSMGY was probably due to declining of bone resorption, without affecting the bone formation in postmenopausal women. PMID- 7865998 TI - [Effect of Chinese herbal preparation on major constituents of bile of gallstones patients]. AB - From 1991 to 1993, 51 patients in 3 groups who had received biliary operation with T tube drainage were selected for observation of dynamic change in bile acid, bilirubin, cholesterol and mucin in the bile within 3 days after taking the Danyihewei granule (DYHW) and Rongshisan (RSS). Result showed that in DYHW group the bile acid increased significantly on the 2nd and 3rd day (P < 0.01), along with significant lowering of bilirubin (P < 0.01) and mucin (P < 0.05, P < 0.01) in 1st through 3rd day. In the RSS group the bile acid remarkably increased on the 3rd day (P < 0.05) with significant reduction of bilirubin (P < 0.01) on 2nd and 3rd day. The control group showed no remarkable change. The bile acid/bilirubin and bile acid/cholesterol ratios all had a dynamic increase with 3 days in treated group. Whereas the control group remained unchanged. Therefore the DYHW and RSS were able to produce a strong inhibitory effect on stone-forming bile through regulation of liver and discharge of bile. PMID- 7865999 TI - [Clinical and experimental study on effect of Chinese herbal drugs on producing prostaglandin in gastric mucosa]. AB - The PG content were determined in 62 cases with peptic ulcer and erosive gastritis before and after the treatment of Chinese herbal drugs. The value of PGE2,PGF1 alpha, 6-keto-PGF1 alpha and TXB2 were 96.25 +/- 28.51, 14.24 +/- 13.26, 10.72 +/- 9.14 and 16.51 +/- 12.24 pg/mg respectively before the treatment and were 121.42 +/- 30.02, 18.59 +/- 18.40, 18.79 +/- 12.61, 8.29 +/- 6.27 pg/mg respectively after the treatment. 6-keto-PGF1 alpha was significantly increased (P < 0.01), TXB2 was decreased (P < 0.01), but there were no significant changes in PGE2 and PGF1 alpha. Experimental study also showed that Chinese Herbal drugs played an important role in protecting indomethacine induced ulcer rats. PMID- 7866000 TI - [Study on erythrocytic immune function in diarrhea patients with spleen deficiency]. AB - The erythrocytic immune function of 40 cases of patients with Spleen Deficiency (SD) and 20 cases of the normal control group were observed, and the former were subdivide into diarrhea group and non-diarrhea group. The results showed that the rosette rate of red cell C3b receptor (C3b-RR) in the SD patients was significantly lower than that of normal group and the rosette rate of red cell immune complex (IC-R) was significantly higher than that of normal group (P < 0.01); the C3b-RR in the diarrhea group was markedly lower than the non-diarrhea group, tce IC-R in the diarrhea group was markedly higher than the non-diarrhea group (P < 0.01), C3b -RR and IC-R correlated positively or negatively to the absorptivity of D-xylose hemoglobin, red blood cell and plasma albumin (P < 0.01). The results pointed out that the mechanism for the reduction of erythrocytic immune function was that the malnutrition in SD patients lowered the C3b receptors or damaged them or reduced their activity. The degree of malabsorption and systemic dysfunction in the diarrhea group was more serious, the erythrocytic immune function in the SD patient was lower. PMID- 7866001 TI - [Preliminary screening of Chinese herbal medicine in inhibiting Helicobacter pylori]. AB - At present Helicobacter pylori (HP) was taken to be closely related to chronic atrophic gastritis and peptic ulcer. 226 patients with symptoms of upper digestive tract by endoscope were examined and chronic atrophic gastritis and peptic ulcer were diagnosed. Mucous membrane from gastric antrum was taken and cultured, and found that 136 cases of 226 patients were HP positive and the rate of positiveness was 60.18%. 200 kinds of Chinese herbal medicine were selected to investigate its inhibitory action on HP. Results indicated that 38 among 200 kinds of Chinese herbal medicine had inhibitory effects on HP, which provided evidence for diagnosis and treatment of chronic atrophic gastritis and peptic ulcer, also for inhibition of HP growth. PMID- 7866002 TI - [Effect of acupuncture on interleukin-2 level and NK cell immunoactivity of peripheral blood of malignant tumor patients]. AB - This paper deals with the observation of acupuncture therapy affecting interleukin-2(IL-2 level and natural killer (NK) cell immunoactivity in the peripheral blood of patients with malignant tumors. In this clinical-laboratory test research, randomized double blind method was used. The patients were divided into an acupuncture treated group (n = 25) and a control group (n = 20). The former group was treated using points, ST36,LI11,RN6 and locations of symptomatic points bilaterally. They received one treatment of 30 minutes daily for 10 days. The results showed that the IL-2 level and NK cell activity were lower than normal in patients with malignant tumor, but there was an increase in the acupuncture group after 10 days of treatment. Significance was found to be remarkable (P < 0.01). The difference between the two groups was also significant (P < 0.01). This increase might be related to the mechanism of acupuncture that adjusting the body's immune function. Thus, acupuncture therapy could enhance the cellular immune function of patients with malignant tumors and providing a beneficial effect in anti-cancer treatment. PMID- 7866003 TI - [Clinical studies on the treatment of coronary heart disease with Valeriana officinalis var latifolia]. AB - Valeriana officinalis var latifolia (VOL), which is the variety of Valeriana officinalis and has the properties to relieve smooth muscle spasm and powerful vasodilation, as demonstrated by animal experiments; no report on its application in treating coronary heart disease (CHD) has been found as yet with VOL. Our preparation of a volatile oil fractionated from its root have been used to treat 82 CHD patients with angina pectoris, among whom ST-T ischemic changes appeared on ECG in 50 cases before treatment. Its total effective rate for the simple angina (without detectable ischemic findings) was 87.80%; the angina with ischemic findings, 88.00%. For comparisons, another 34 patients with the same conditions, 24 cases among them belonged to the angina with ischemic findings, were treated with a composite injection of Salvia miltiorrhiza (SMCo); the total effective rates for the simple angina and for the angina with ischemic findings were 41.18% and 37.50% respectively. The differences between VOL and SMCo were both highly significant (P < 0.001, P < 0.01) either in the simple angina or in the angina with ischemic findings. The results showed VOL was superior to SMCo on matter in the remission of symptoms, decreasing the attack frequency and shortening the duration of angina, or in restoring the blood supply to ischemic myocardium. In addition, it was discovered that VOL could lower plasma lipids as well. No toxic actions to liver, kidney, hemopoietic tissue, have been found. PMID- 7866004 TI - [Experimental study of kangli san in treating viral hyperpyrexia]. AB - The hypothermic effect of Kangli San (KLS) on the model of rabbit viral hyperpyrexia caused by rabbit hemorrhagic fever virus was studied. Intraperitoneal injection of 200% KLS (4g/kg) could inhibit the pyrogenic action of the virus efficiently. The results showed that KLS could decrease the function of pyrogenic transmitters such as PGE2 and cAMP etc. in cerebrospinal fluid. PMID- 7866006 TI - [Research developments of sa sang medicine in Korea]. PMID- 7866005 TI - [Study of effects of Chinese herbal prescription combined with copper, iron on malignancy of cancer cells]. AB - BALB/c mice bearing ascitic liver cancer were used, and Chinese herbal prescriptions combined with Cu and Fe (CHCF) was given by gavage continuously for 10 days, and some cell biological parameters were measured; furthermore, the ascitic cancer cells (control and treated group) were removed, and retransplanted to another mice and observed. The results showed that in CHCF treated group, DNA content of the cancer cells was decreased, and the proliferation index (PI) was reduced (control: 83.4 +/- 2.6, CHCF group: 78.8 +/- 1.5; or control: 67.2 +/- 1.3, CHCF group: 64.2 +/- 1.6, P < 0.05). The number of the cancer cells in G1 phase increased obviously, but, those of S+G2M phases decreased considerably (P < 0.05-0.01); on the DNA histogram, the diploid peak became higher and bigger, but multiploid peaks became smaller. Furthermore, retransplanted experiments showed that in 2/10 animals, the tumor did not grow, the growth inhibition rate was 71.7%-88.3%; and the survival period of retransplanted animals was prolonged significantly (from 26.1 +/- 11.8 days to 38.1 +/- 9.6 days, or to 39.6 +/- 7.2 days, P < 0.01); the increase in life span was 46%-52% respectively. These results suggested that CHCF could decrease the malignancy of liver cancer cells in mice. PMID- 7866007 TI - [Study on inotropic action of berberine]. PMID- 7866008 TI - [Pathogenesis of renal proteinuria based on the traditional Chinese medicine and exploration in its prescriptions with modern pharmacology]. PMID- 7866009 TI - Do practitioners owe greater loyalty to employers or patients? PMID- 7866010 TI - Euthanasia: why people want to die earlier. PMID- 7866011 TI - Choosing continence aids. AB - Caring for people with continence problems is challenging, rewarding and every nurse's concern. This article will discuss the choice and use of continence related aids. Future articles will examine aids for containing incontinence, their place in high quality continence care, and the importance of value for money. PMID- 7866012 TI - Isolated limb perfusion. AB - Growing concern over the rising incidence of malignant melanoma has brought about a need for information on this disorder and the treatment available. Isolated limb perfusion is a relatively new technique used in only a few hospitals. An increased knowledge base will lead to a better understanding of the nursing care required and to a more in-depth care plan. PMID- 7866013 TI - Elder abuse and neglect. AB - Elder abuse is now being recognised as a serious social problem. This article discusses the difficulties in defining elder abuse and describes the characteristics of the abused and the abuser. It then suggests how nurses may recognise abuse and outlines the interventions that may be employed. PMID- 7866014 TI - Implications of the EC Manual Handling of Loads Directive for nurse managers. AB - The European Community has introduced new regulations designed to stop people being injured when moving loads at work. These rules came into effect on 1 January 1993. So far, however, many managers have done nothing about them. If nurses are injured, their employers may be liable to pay large sums in compensation. Managers must start to take these issues seriously. PMID- 7866015 TI - Ethics: an emerging management issue. AB - This article considers the potential reasons for the increasing importance of ethical concerns in the context of nursing management and its implications. PMID- 7866016 TI - The role of the patient in standard setting and audit. AB - This article examines some of the problems and issues involved in quality assurance of nursing care and the measurement of patients' views of health care. It argues that these two endeavours can and indeed should be related. PMID- 7866017 TI - Nursing intuition: can it be researched? AB - Drawing on the work of Gilligan (1982) and Heidegger (1962), this article explores the topic of intuition. It examines whether nursing intuition can be researched, if it is possible to develop a language of intuition, and if it is related to 'hands-on' experience. PMID- 7866018 TI - Finding funds for nursing research. PMID- 7866019 TI - A 'cycle of care': a model of community and hospital HIV/AIDS services. PMID- 7866020 TI - Do we take self-advocacy seriously? AB - A training pack has been developed to help staff introduce the concept of self advocacy to patients who are disabled or have learning difficulties so that they may challenge service providers. It should be possible to provide working and living environments in which respect for one another's humanity can be shared. PMID- 7866021 TI - Elevation of cytosolic calcium precedes anoxic gene expression in maize suspension-cultured cells. AB - Based on pharmacological evidence, we previously proposed that intracellular Ca2+ mediates the perception of O2 deprivation in maize seedlings. Herein, using fluorescence imaging and photometry of Ca2+ in maize suspension-cultured cells, the proposal was further investigated. Two complementary approaches were taken: (1) real time analysis of anoxia-induced changes in cytosolic Ca2+ concentration ([Ca]i) and (2) experimental manipulation of [Ca]i and then assay of the resultant anoxia-specific responses. O2 depletion caused an immediate increase in [Ca2+]i, and this was reversible within a few seconds of reoxygenation. The [Ca]i elevation proceeded independent of extracellular Ca2+. The kinetics of the Ca2+ response showed that it occurred much earlier than any detectable changes in gene expression. Ruthenium red blocked the anoxic [Ca]i elevation and also the induction of adh1 (encoding alcohol dehydrogenase) and sh1 (encoding sucrose synthase) mRNA. Ca2+, when added along with ruthenium red, prevented the effects of the antagonist on the anoxic responses. Verapamil and bepridil failed to block the [Ca]i rise induced by anoxia and were equally ineffective on anoxic gene expression. Caffeine induced an elevation of [Ca]i as well as ADH activity under normoxia. The data provide direct evidence for [Ca]i elevation in maize cells as a result of anoxia-induced mobilization of Ca2+ from intracellular stores. Furthermore, any manipulation that modified the [Ca]i rise brought about a parallel change in the expression of two anoxia-inducible genes. Thus, these results corroborate our proposal that [Ca]i is a physiological transducer of anoxia signals in plants. PMID- 7866022 TI - Developmental expression of the arabidopsis cyclin gene cyc1At. AB - In eukaryotes, the control of cell cycle progression is exercised by heteromeric protein kinase complexes composed of a cell cycle-dependent, kinase-related subunit (Cdc2) and a cyclin subunit. To explore the possibility that cyclin transcription plays a role in the developmental regulation of cell division, we examined the spatial and temporal expression of a cyclin gene (cyc1At) in Arabidopsis. In root and shoot apical meristems and during embryogenesis, cyc1At expression is almost exclusively confined to dividing cells. A cell-specific pattern of cyc1At expression was noticed in root meristems. We examined the effects of induction of cell division of differentiated cells on cyc1At expression. During lateral root formation, induction of cyc1At expression is a very early event and was detected before anatomical modifications were visible. Treatment of roots with oryzalin, which blocks cell division in metaphase, did not inhibit the auxin induction of cyc1At, suggesting that induction of cyc1At expression precedes the completion of the first division cycle after induction of lateral roots. In tobacco protoplasts, an increase in cyc1At expression was observed only when cell division was induced. Together, the results suggest that Cyc1At accumulation in Arabidopsis is transcriptionally regulated and might be one of the limiting factors for the activation of cell division. PMID- 7866023 TI - Comparison of MADS box gene expression in developing male and female flowers of the dioecious plant white campion. AB - The MADS box motif is common to genes that regulate the pattern of flower development. To determine whether MADS box genes also play a role in differentiation of the sexes in dioecious plants, we isolated cDNAs (SLM1 to SLM5, for Silene latifolia MADS) with MADS box homology from transcripts of male flower buds of the model dioecious species white campion and compared their expression in developing female and male flowers. SLM1 had extensive sequence similarity to the snapdragon MADS box gene PLENA, SLM2 to GLOBOSA, SLM3 to DEFICIENS, and both SLM4 and SLM5 were similar to SQUAMOSA. Each of the white campion MADS box genes was expressed in the same floral whorls as their respective most homologous snapdragon genes. The sex of the plant affected the pattern of SLM2 and SLM3 expression in the petal and stamen whorls, resulting in a smaller fourth whorl in male flowers than in female flowers. This was correlated with repressed gynoecium development in male flowers. The expression of SLM4 and SLM5 in both sexes differed from that of SQUAMOSA in one important aspect. Unlike SQUAMOSA, they were expressed in inflorescence meristems. This may reflect differences in growth pattern between white campion and snapdragon. PMID- 7866024 TI - The elicitor-inducible alfalfa isoflavone reductase promoter confers different patterns of developmental expression in homologous and heterologous transgenic plants. AB - In legumes, the synthesis of infection- and elicitor-inducible antimicrobial phytoalexins occurs via the isoflavonoid branch of the phenylpropanoid pathway. To study transcriptional regulation of isoflavonoid pathway-specific genes, we have isolated the gene encoding isoflavone reductase (IFR), which is the enzyme that catalyzes the penultimate step in the synthesis of the phytoalexin medicarpin in alfalfa. Chimeric gene fusions were constructed between 765- and 436-bp promoter fragments of the IFR gene and the beta-glucuronidase reporter gene and transferred to alfalfa and tobacco by Agrobacterium-mediated transformation. Both promoter fragments conferred elicitor-mediated expression in cell suspension cultures derived from transgenic plants of both species and fungal infection-mediated expression in leaves of transgenic alfalfa. Developmental expression directed by both promoter fragments in transgenic alfalfa was observed only in the root meristem, cortex, and nodules, which is consistent with the accumulation of endogenous IFR transcripts. However, in transgenic tobacco, expression from the 765-bp promoter was observed in vegetative tissues (root meristem and cortex, inner vascular tissue of stems and petioles, leaf tips, and stem peripheries adjacent to petioles) and in reproductive tissues (stigma, placenta, base of the ovary, receptacle, seed, tapetal layer, and pollen grains), whereas the 436-bp promoter was expressed only in fruits, seed, and pollen. These data indicate that infection/elicitor inducibility of the IFR promoter in both species and developmental expression in alfalfa are determined by sequences downstream of position -436, whereas sequences between -436 and -765 confer a complex pattern of strong ectopic developmental expression in the heterologous species that lacks the isoflavonoid pathway. PMID- 7866025 TI - Molecular dissection of GT-1 from Arabidopsis. AB - We isolated and characterized an Arabidopsis cDNA encoding the DNA binding protein GT-1. This protein factor, which contains 406 amino acids, is highly homologous to the previously described tobacco DNA binding protein GT-1a/B2F but is 26 amino acids longer. Recombinant Arabidopsis GT-1, which was obtained from in vitro translation, bound to probes consisting of four copies of pea small subunit of ribulose bisphosphate carboxylase rbcS-3A box II and required the same GGTTAA core binding site as the binding activity of an Arabidopsis nuclear protein preparation. However, unlike the truncated tobacco GT-1a prepared from Escherichia coli extracts, the full-length Arabidopsis GT-1 bound to pea rbcS-3A box III and Arabidopsis chlorophyll a/b binding protein CAB2 light-responsive elements, both of which contain GATA motifs. Deletion and mutational analyses suggested that the predicted trihelix region of GT-1 is essential for DNA binding. Moreover, GT-1 binds to target DNA as a dimer, and its C-terminal region contains a putative dimerization domain that enhances the binding activity. Transient expression of the GT-1::beta-glucuronidase fusion protein in onion cells revealed the presence of a nuclear localization signal(s) within the first 215 amino acids of GT-1. PMID- 7866026 TI - Pollen tube growth is coupled to the extracellular calcium ion flux and the intracellular calcium gradient: effect of BAPTA-type buffers and hypertonic media. AB - Lily pollen tubes possess a steep, tip-focused intracellular Ca2+ gradient and a tip-directed extracellular Ca2+ influx. Ratiometric ion imaging revealed that the gradient extends from above 3.0 microM at the apex to approximately 0.2 microM within 20 microns from the tip, while application of the Ca(2+)-specific vibrating electrode indicated that the extracellular influx measured between 1.4 and 14 pmol cm-2 sec-1. We examined the relationship between these phenomena and their role in tube growth by using different 1,2-bis(o-aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA)-type buffers and hypertonic media. Injection of active BAPTA-type buffers or application of elevated levels of sucrose reversibly inhibited growth, destroyed tip zonation of organelles, and modified normal patterns of cytoplasmic streaming. Simultaneously, these treatments dissipated both the intracellular tip-focused gradient and the extracellular Ca2+ flux. Of the BAPTA-type buffers, 5,5'-dibromo-BAPTA (dissociation constant [Kd] is 1.5 microM) and 4,4'-difluoro-BAPTA (Kd of 1.7 microM) exhibited greater activity than those buffers with either a higher affinity (5,5'-dimethyl-BAPTA, Kd of 0.15 microM; BAPTA, Kd of 0.21 microM; 5,5'-difluoro-BAPTA, Kd of 0.25 microM) or lower affinity (5-methyl, 5'-nitro-BAPTA, Kd of 22 microM) for Ca2+. Our findings provide evidence that growing pollen tubes have open Ca2+ channels in their tip and that these channels become inactivated in nongrowing tubes. The studies with elevated sucrose support the view that stretching of the apical plasma membrane contributes to the maintenance of the Ca2+ signal. PMID- 7866027 TI - A superfamily of S locus-related sequences in Arabidopsis: diverse structures and expression patterns. AB - Six sequences that are closely related to the S gene family of the largely self incompatible Brassica species have been identified in self-fertilizing Arabidopsis. The sequences define four genomic regions that map to chromosomes 1 and 3. Of the four functional genes identified, only the previously reported Arabidopsis AtS1 gene was expressed specifically in papillar cells and may function in pollination. The remaining three genes, including two novel genes designated ARK2 and ARK3, encode putative receptor-like serine/threonine protein kinases that are expressed predominantly in vegetative tissues. ARK2 promoter activity was detected exclusively in above-ground tissues, specifically in cotyledons, leaves, and sepals, in correlation with the maturation of these structures. ARK3 promoter activity was detected in roots as well as above-ground tissues but was limited to small groups of cells in the root-hypocotyl transition zone and at the base of lateral roots, axillary buds, and pedicels. The nonoverlapping patterns of expression of the ARK genes and the divergence of their sequences, particularly in their predicted extracellular domains, suggest that these genes perform nonredundant functions in specific aspects of development or growth of the plant body. PMID- 7866028 TI - A mutation in Arabidopsis that leads to constitutive expression of systemic acquired resistance. AB - Systemic acquired resistance (SAR) is a nonspecific defense response in plants that is associated with an increase in the endogenous level of salicylic acid (SA) and elevated expression of pathogenesis-related (PR) genes. To identify mutants involved in the regulation of PR genes and the onset of SAR, we transformed Arabidopsis with a reporter gene containing the promoter of a beta 1,3-glucanase-encoding PR gene (BGL2) and the coding region of beta-glucuronidase (GUS). The resulting transgenic line (BGL2-GUS) was mutagenized, and the M2 progeny were scored for constitutive GUS activity. We report the characterization of one mutant, cpr1 (constitutive expressor of PR genes), that was identified in this screen and shown by RNA gel blot analysis also to have elevated expression of the endogenous PR genes BGL2, PR-1, and PR-5. Genetic analyses indicated that the phenotype conferred by cpr1 is caused by a single, recessive nuclear mutation and is suppressed in plants producing a bacterial salicylate hydroxylase, which inactivates SA. Furthermore, biochemical analysis showed that the endogenous level of SA is elevated in the mutant. Finally, the cpr1 plants were found to be resistant to the fungal pathogen Peronospora parasitica NOCO2 and the bacterial pathogen Pseudomonas syringae pv maculicola ES4326, which are virulent in wild type BGL2-GUS plants. Because the cpr1 mutation is recessive and associated with an elevated endogenous level of SA, we propose that the CPR1 gene product acts upstream of SA as a negative regulator of SAR. PMID- 7866029 TI - A knotted1-like homeobox gene in Arabidopsis is expressed in the vegetative meristem and dramatically alters leaf morphology when overexpressed in transgenic plants. AB - The homeobox gene knotted1 (kn1) was first isolated by transposon tagging a dominant leaf mutant in maize. Related maize genes, isolated by virtue of sequence conservation within the homeobox, fall into two classes based on sequence similarity and expression patterns. Here, we report the characterization of two genes, KNAT1 and KNAT2 (for knotted-like from Arabidopsis thaliana) that were cloned from Arabidopsis using the kn1 homeobox as a heterologous probe. The homeodomains of KNAT1 and KNAT2 are very similar to the homeodomains of proteins encoded by class 1 maize genes, ranging from 78 to 95% amino acid identity. Overall, the deduced KNAT1 and KNAT2 proteins share amino acid identities of 53 and 40%, respectively, with the KN1 protein. Intron positions are also fairly well conserved among KNAT1, KNAT2, and kn1. Based on in situ hybridization analysis, the expression pattern of KNAT1 during vegetative development is similar to that of class 1 maize genes. In the shoot apex, KNAT1 transcript is localized primarily to the shoot apical meristem; down-regulation of expression occurs as leaf primordia are initiated. In contrast to the expression of class 1 maize genes in floral and inflorescence meristems, the expression of KNAT1 in the shoot meristem decreases during the floral transition and is restricted to the cortex of the inflorescence stem. Transgenic Arabidopsis plants carrying the KNAT1 cDNA and the kn1 cDNA fused to the cauliflower mosaic virus 35S promoter were generated. Misexpression of KNAT1 and kn1 resulted in highly abnormal leaf morphology that included severely lobed leaves. The expression pattern of KNAT1 in the shoot meristem combined with the results of transgenic overexpression experiments supports the hypothesis that class 1 kn1-like genes play a role in morphogenesis. PMID- 7866030 TI - Sequence analysis and expression patterns divide the maize knotted1-like homeobox genes into two classes. AB - The homeobox of the knotted1 (kn1) gene was used to isolate 12 related sequences in maize. The homeodomains encoded by the kn1-like genes are very similar, ranging from 55 to 89% amino acid identity. Differences outside the precisely conserved third helix allowed us to group the genes into two classes. The homeodomains of the seven class 1 genes share 73 to 89% identical residues with kn1. The four class 2 genes share 55 to 58% identical residues with kn1, although the conservation within the class is greater than 87%. Expression patterns were analyzed by RNA gel blot analysis. Class 1 genes were highly expressed in meristem-enriched tissues, such as the vegetative meristem and ear primordia. Expression was not detectable in leaves. The class 2 genes were expressed in all tissues, although one was abundantly expressed in roots. The genes were mapped using recombinant inbred populations. We determined that clusters of two to three linked genes are present on chromosomes 1 and 8; otherwise, the genes are distributed throughout the genome. Four pairs of genes, similar in both sequence and expression patterns, mapped within duplicated regions of the genome. PMID- 7866031 TI - A soybean 101-kD heat shock protein complements a yeast HSP104 deletion mutant in acquiring thermotolerance. AB - A cDNA clone encoding a 101-kD heat shock protein (HSP101) of soybean was isolated and sequenced. Genomic DNA gel blot analysis indicated that the corresponding gene is a member of a multigene family. The mRNA for HSP101 was not detected in 2-day-old etiolated soybean seedlings grown at 28 degrees C but was induced by elevated temperatures. DNA sequence comparison has shown that the corresponding gene belongs to the Clp (caseinolytic protease) (or Hsp100) gene family, which is evolutionarily conserved and found in both prokaryotes and eukaryotes. On the basis of the spacer length between the two conserved ATP binding regions, this gene has been identified as a member of the ClpB subfamily. Unlike other Clp genes previously isolated from higher plants, the expression of this soybean Hsp101 gene is heat inducible, and it does not have an N-terminal signal peptide for targeting to chloroplasts. Transformation of the soybean Hsp101 gene into a yeast HSP104 deletion mutant complemented restoration of acquired thermotolerance, a process in which cells survive an otherwise lethal heat stress after they are given a permissive heat treatment. PMID- 7866033 TI - Cloning a putative self-incompatibility gene from the pollen of the grass Phalaris coerulescens. AB - In Phalaris coerulescens, gametophytic self-incompatibility is controlled by two unlinked genes: S and Z. A probable S gene has now been isolated and sequenced. This represents a novel self-incompatibility gene isolated from pollen in the multilocus system of a monocotyledonous plant. The gene is approximately 3 kb long, split by five introns, and exclusively expressed in the mature pollen. The deduced amino acid sequences from the S1, S2, and part of the S4 alleles showed that the protein has a variable N terminus and a conserved C terminus. The sequence of a complete mutant at the S locus indicated that mutations in the conserved C terminus, a thioredoxin-like region, led to loss of function. We propose that the gene has two distinct sections, a variable N terminus determining allele specificity and a conserved C terminus with the catalytic function. The gene structure and its deduced protein sequences strongly suggest that this monocotyledon has developed a self-incompatibility system entirely different from those operating in the dicotyledons. The possible interactions between S and Z genes in both pollen and stigma are discussed. PMID- 7866032 TI - An Arabidopsis heat shock protein complements a thermotolerance defect in yeast. AB - The heat shock protein Hsp104 of the yeast Saccharomyces cerevisiae plays a key role in promoting survival at extreme temperatures. We found that when diverse higher plant species are exposed to high temperatures they accumulate proteins that are antigenically related to Hsp104. We isolated a cDNA corresponding to one of these proteins from Arabidopsis. The protein, AtHSP101, is 43% identical to yeast Hsp104. DNA gel blot analysis indicated that AtHSP101 is encoded by a single- or low-copy number gene. AtHsp101 mRNA was undetectable in the absence of stress but accumulated to high levels during exposure to high temperatures. When AtHSP101 was expressed in yeast, it complemented the thermotolerance defect caused by a deletion of the HSP104 gene. The ability of AtHSP101 to protect yeast from severe heat stress strongly suggests that this HSP plays an important role in thermotolerance in higher plants. PMID- 7866034 TI - Carbohydrate moiety of the Petunia inflata S3 protein is not required for self incompatibility interactions between pollen and pistil. AB - For Petunia inflata and Nicotiana alata, which display gametophytic self incompatibility, S proteins (the products of the multiallelic S gene in the pistil) have been shown to control the pistil's ability to recognize and reject self-pollen. The biochemical mechanism for rejection of self-pollen by S proteins has been shown to involve their ribonuclease activity; however, the molecular basis for self/non-self recognition by S proteins is not yet understood. Here, we addressed whether the glycan chain of the S3 protein of P. inflata is involved in self/non-self recognition by producing a nonglycosylated S3 protein in transgenic plants and examining the effect of deglycosylation on the ability of the S3 protein to reject S3 pollen. The S3 gene was mutagenized by replacing the codon for Asn-29, which is the only potential N-glycosylation site of the S3 protein, with a codon for Asp, and the mutant S3 gene was introduced into P. inflata plants of the S1S2 genotype. Six transgenic plants that produced a normal level of the nonglycosylated S3 protein acquired the ability to reject S3 pollen completely. These results suggest that the carbohydrate moiety of the S3 protein does not play a role in recognition or rejection of self-pollen and that the S allele specificity determinant of the S3 protein and those S proteins that contain a single glycan chain at the same site as the S3 protein must reside in the amino acid sequence itself. PMID- 7866036 TI - [Malaria, at the end of the century]. PMID- 7866035 TI - A single homogeneous form of ATP6 protein accumulates in petunia mitochondria despite the presence of differentially edited atp6 transcripts. AB - Transcripts encoding ATP synthase subunit 6 (ATP6) in petunia mitochondria were shown to be edited at 15 sites, leading to 14 amino acid changes. Certain sites are partially edited, including a site that introduces a new translation termination codon that is 13 codons upstream of the genomically encoded stop codon. Transcripts lacking the new stop codon are present in an approximately 2.5:1 ratio to transcripts carrying the stop codon created by RNA editing. To investigate whether partially edited transcripts are represented as proteins, we generated an antibody against a 12-residue peptide that is specific for translation products of unedited transcripts. This antibody did not recognize any ATP6 protein in either total mitochondrial protein preparations or ATP6 samples purified by organic solvent extraction and reverse phase HPLC procedures. According to analysis by mass spectrometry, only one form of ATP6 protein accumulates in mitochondria despite the presence of abundant partially edited transcripts. Partially edited atp6 transcripts were associated with ribosomes, suggesting that a screening mechanism(s) acts cotranslationally or post translationally to exclude the expression of incompletely edited transcripts. PMID- 7866037 TI - [Vertical transmission of the human T-cell leukemia virus in an endemic area. An epidemiological study in children from 0 to 5 years in Gabon]. AB - A seroepidemiological survey was conducted in a representative population of children aged 0-5 in Gabon. Breast-feeding appears to an important mode of HTLV vertical transmission. Owing to other epidemiological data in population of gabonese adults allow us to think that breast-feeding related transmission and sexual transmission seem to occur in equal proportion in the global HTLV transmission in that area of endemicity. PMID- 7866038 TI - [Antibiotic sensitivity of gram negative bacilli isolated from urinary tract infections at NUHC of Cotonou (Benin) from March to December 1992]. AB - Eleven antibiotics were tested against 1,194 Gram negative bacilli isolated from urinary tract infections at the National University Hospital Center at Cotonou. Among the betalactams tested, only cefotaxime remained active against most of the bacteria tested: 90% of the strains of Escherichia coli and 75% of the strains of Enterobacter cloacae were sensitive. Ampicilline, on the other hand, had lost its activity even on strains which are usually the most susceptible. Thirteen percent of the E. coli strains were sensitive. This reduction in antibiotic activity against bacterial strains in Cotonou, which concerned to various degrees the tetracyclines, chloramphenicol, cotrimoxazole, is less pronounced for the amino sides (gentamicine and netilmicine), and the quinolones of which nalidixique acid was active against 83.9% of the strains of E. coli. The low frequency of isolation of wild type strains (sensitive to betalactams) is probably the consequence of strong selection pressure due to a massive, and uncontrolled use of antibiotics in Cotonou. PMID- 7866039 TI - [First isolation of Borrelia afzelii in France (Marne) from Ixodes ricinus]. AB - A strain of Borrelia has been isolated from Ixodes ricinus in France (Marne). The DNA analysis by PCR showed that it is identical to B. afzelii. PMID- 7866040 TI - [Triple shigellosis in the same patient contracted during operation "Turquoise" in Rwanda]. AB - We report a case of shigellosis observed in a young French sanitary assistant, returning from a refugees camp in Goma after a 5-week stay. Three different species were isolated from stool samples: Shigella flexneri, S. boydii and S. sonnei. This observation raises the matter of a chemical prophylaxis during a short stay in developing countries where sanitary conditions are poor. PMID- 7866041 TI - [Entamoeba histolytica (Schaudinn 1903) and Entamoeba dispar (E. Brumpt 1925) are 2 different species]. AB - On the basis of epidemiologic and clinical data in humans, and of experimental studies in kittens, E. Brumpt in 1925 showed that Entamoeba histolytica producing quadrinucleate cysts was a complex of 2 species. He differentiated a pathogenic and invasive form, from a non pathogenic and non invasive one that he called Entamoeba dispar. His explanation gained little support until recently, when Sargeaunt reported a study of isoenzyme typing and allow then the classification of amoebae resembling E. histolytica in pathogenic and non pathogenic species. Monoclonal antibodies and PCR have recently been used and have shown to react specifically with the two forms of amoebae. Genetic evidence has also demonstrated that the pathogenic and non pathogenic amoebae represent different species. PMID- 7866042 TI - [Chronic osteomyelitis at Dantec UHC , at Dakar]. AB - The authors report 82 cases of osteomyelitis treated and followed up at the CHU Le Dantec, from March 1979 to September 1991. The patients were young, with an average age of 18 and a half years. Some susceptibility factors were identified: malnutrition (12.20%) and sickle cell anemia (26.83%). The infection was more frequently located on long bones of the lower limber (62.77%) and mainly on the metaphysis. Fistula forms with sequestra were the most frequent ones. Sixty-six patients were healed right after the first operation, 13 after two operations, 3 after three operations, the laters were mainly relapsing cases related to insufficient curreting of the infected bone or persisting sequestrum. PMID- 7866043 TI - [Foreign bodies of the esophagus. Apropos of 130 cases]. AB - This study reports a series of 130 foreign bodies of the oesophage treated at the Gabriel Toure Hospital in Bamako. We tried to determine their nature, their intra oesophage struck period, and the possible consequences being observed. At the some time the age and the sex are given. A predominance of foreign bodies in a male sex child (67%) is found, as it usually in literature. Complications are rare, this is a public health issue whose solution lies in prevention. We are the only specialized center from Mali, therefore we are sometimes confronted to stuck and very old foreign bodies. In spite of that, no death were registered. PMID- 7866044 TI - [Parasitological and clinical response to amodiaquine versus chloroquine in the treatment of Plasmodium falciparum malaria in children in an endemic area]. AB - The therapeutic management of malaria in endemic regions is now hampered not only by the limited number of antimalarial agents, but also by the appearance of chemoresistant plasmodial strains and by the sometimes severe adverse effects related to the use of some of these drugs. Between January and July 1993, 100 patients presenting with symptomatic Plasmodium falciparum malaria were randomised to receive amodiaquine or chloroquine at the dose of 30 mg/kg for 3 days. The objective of this study was to compare the efficacy and safety of these two 4-aminoquinolines in the treatment of uncomplicated malaria. The parasite clearance was 4.87 (+/- 0.33) days in the amodiaquine group and 5.55 (+/- 0.31) days in the chloroquine group. All subjects in both groups were afebrile by D7. Cutaneous adverse effects, such as pruritus, were reported with both amodiaquine (3.2%) and chloroquine (6.8%). Amodiaquine was found to be significantly more effective than chloroquine in terms of parasite clearance on D7. The therapeutic failure rate was 0% for amodiaquine versus 16.3% for chloroquine. At a time when chemoresistance of Plasmodium falciparum, especially chloroquine-resistance, has spread to malarial endemic zones, amodiaquine should be very widely indicated in the treatment of simple malaria due to its excellent efficacy and good safety. PMID- 7866045 TI - [Pulmonary involvement with a favorable course during Loa loa filariasis]. AB - We report a case of pulmonary infiltrate in filariasis due to Loa loa in a 52 years old patient, living in Cameroon. Antifilarial treatment with ivermectin then diethylcarbamazine led to a rapid resoluting of the pulmonary abnormalities. It is the fifth case of lung disease during filariasis Loa loa. PMID- 7866046 TI - [Use of health facilities by children from 0 to 5 years in Togo. Results of an epidemiological study carried out at a RHC (Atakpame)]. AB - Through a prospective survey coordinated by the CIE of Paris, and carried at a semi-urban regional hospital (Atakpame), the authors studied the use of health structures by inpatient and outpatient consulting children. Questionnaires were filled for the 112 children of the study. Results were as follows: There is a maladjustment between recruitment at the regional hospital and its real mission (emergency cases and special health care). Thus only 13.3% of children were seen for an emergency, and 4.5% admitted for special health case. In the majority of cases (69.4%), the health state of patients was not alarming. Improper channelling of the patients is responsible for this condition. 79.4% of children consult directly at the hospital without prior consultation at the "peripheral" health centers. The regional health center thus finds itself overburdened, whereby long waiting periods before consultation (> 300 mn for certain patients), and delay in the management of referred patients. PMID- 7866047 TI - [Malaria in children at the Sihanoukville Hospital (Cambodia)]. AB - The authors have studied 68 children admitted with malaria in Sihanoukville Hospital (Cambodia) from December 1992 to April 1993. Sihanoukville is located on coast of the country, in a hypoendemic area with seasonal transmission occurring during this study. The patients lived in urban (1/3) or in rural areas (2/3). Plasmodium (P.) vivax alone was found in 15 cases. Among them, two patients presented with severe malaria, but chloroquine was efficient in all cases. P. falciparum with or without P. vivax, was predominant (53 cases). Most of these cases were severe, according to WHO criteria (n = 43), from which 11 deaths occurred (25%). There were 26 cases of cerebral malaria, with a death rate of 34.6%. A severe course was observed with the following criteria: prostration or coma (p = 0.029), severe anaemia (p = 0.037) and hyperparasitaemia (p = 0.00078). A significant longer delay for treatment and admission was noted among rural patients (p = 0.023 and p = 0.011 respectively). In those children, hyperparasitaemia, poor clinical status on admission and lethality were more frequent. The clinical course was not clearly improved with the addition of erythromycin in the quinine regimen. No quinine resistance was observed in this data. PMID- 7866048 TI - [Vectorial fauna at the site of the future dam at Memve'ele(Cameroon)]. AB - The present study was designed to assess the health risk of the future hydroelectric dam of Memve'ele with reference to vector-borne diseases. Entomological and malacological surveys were carried out in the project area. The main vectors collected were Anopheles gambiae and An. nili for malaria; Simulium damnosum for onchocerciasis; Glossina palpalis for trypanosomiasis; Chrysops dimidiata and C. silacea for loasis. No snail host of schistosome was reported. The risk of introduction of the diseases they transmit are discussed. PMID- 7866049 TI - [Anopheles of Senegal. An annotated and illustrated list]. AB - Twenty species of Anopheles are presently known from Senegal. An. gambiae, An. arabiensis, An. pharoensis, An. rufipes and An. ziemanni have an extensive distribution. Probably because of climatic change, An. funestus is no more found in some areas and An. paludis tend to disappear. An. melas is located in coastal areas. The other species, namely An. coustani, An. brohieri, An. brunnipes, An. domicola, An. flavicosta, An. freetownensis, An. hancocki, An. maculipalpis, An. nili, An. pretoriensis, An. squamosus and An. wellcomei, are mainly found in southern Senegal. Only An. gambiae, An. arabiensis and An. funestus are of epidemiological significance as vectors of malaria and bancroftian filariasis. Twelve arboviruses have been isolated from eight Anopheles species. Each Anopheles species is illustrated and an identification key is given. PMID- 7866050 TI - [Importance and role of spreading larvicides on the soil in river beds for the control program against onchocerciasis in west Africa]. AB - The control of blackfly is based on larvicide spraying in rivers where the insects breed and their larval stages are vulnerable. The first technique for large-scale operations, consists of using aircraft in the same way as for mosquito control and crop protection operations. The second technique, which will be discussed in this paper, consists of ground treatment of rivers, either directly with a container or with a spraying pump or by boat spraying insecticide in cross strip. In areas of West Africa where onchocerciasis is still prevalent, ground treatment is done to support aerial operations and to a lesser extent to control nuisance in areas where the endemicity of the disease is low. In onchocerciasis-freed zones, control of blackfly aims only at suppressing the nuisance in order to enhance the socio-economic development in areas at unfair disadvantage. This distinction is important for determining the responsibilities of various groups. Vector control to interrupt the transmission of onchocerciasis is the mandate of OCP while the control of nuisance is the responsibility, depending on the circumstances, of the private sector, the government and/or village communities. In this paper, we have attempted to highlight the objectives of such treatments, the responsibilities of various groups and the prospects in West African countries located in the Onchocerciasis Control Programme area. We also present the situation of ground larviciding in countries outside the Programme, in temperate as well as tropical conditions, in order to provide some basis for the development of ground treatment strategies in the OCP area. PMID- 7866051 TI - [Importance of socio-cultural data for accessibility of health care and observance of treatment in leprosy. Example of the Zarma region in Niger]. AB - From an epidemiological point of view leprosy remains a problem of public health. Various factors influence the accessibility to health care and the observance of treatment. The study carried out in Niger shows that beyond the stigmatism associated with the disease, the most important factors concern the difference between scientific and popular etiology and semiology. In the face of such problems it is necessary, from a theoretical point of view, to make anthropological enquiries based on the theme of the different representations of this pathology, and from a practical point of view, to examine the possibility of the participation of former patients in public health teams. PMID- 7866052 TI - Antineutrophil cytoplasmic autoantibody--associated glomerulonephritis: potentially reversible disease. AB - Renal vasculitis frequently presents itself as rapidly progressive glomerulonephritis, but its diagnosis may be hampered by the difficulty in demonstrating classic vasculitic lesions in renal biopsy specimens. Early diagnosis of renal vasculitis has been greatly enhanced by the advent of antineutrophil cytoplasmic autoantibodies (ANCA). On indirect immunofluorescence microscopy, cytoplasmic ANCA (C-ANCA) show cytoplasmic staining of alcohol-fixed neutrophils and are directed against proteinase 3 in the primary granules of neutrophils. Perinuclear ANCA (P-ANCA) show perinuclear staining due to redistribution of granular antigens, and are specific for myeloperoxidase in the primary granules of the vasculitic patients. C-ANCA are most frequently associated with Wegener's granulomatosis and P-ANCA, with "idiopathic" necrotizing and crescentic glomerulonephritis (renal-limited disease). Patients with microscopic polyarteritis may be associated with either P-ANCA or C-ANCA and there is a considerable overlap between Wegener's granulomatosis and microscopic polyarteritis in both clinical features and serologic patterns. ANCA are not only the markers for vasculitis but may also play a role in the pathogenesis by activating the neutrophils to attack target blood vessels. There is also a crude correlation between ANCA titer and the activity of vasculitis. ANCA-associated vasculitis responds well to steroid and/or cyclophosphamide therapy. Renal failure in these patients is frequently reversible if treated early. Long-term patient and kidney survival rates are good with proper treatment and are far better than those of the other causes of rapidly progressive glomerulonephritis. Potential morbidity of steroid and immunosuppressive therapy should be reduced by the use of low effective doses and by close clinical observation and management. PMID- 7866053 TI - Sequence determination of hepatitis C virus genome isolated from Taiwan. AB - The partial genome sequence of the hepatitis C virus (HCV) was determined in the serum of a Taiwanese patient with chronic community-acquired type C hepatitis. The cDNA fragments synthesized with the HCV RNA as a template were amplified by polymerase chain reaction using specific oligonucleotide primers. The amplified fragments represented the regions coding for the putative core, matrix and envelope proteins as well as the N-terminal amino acid sequence of the nonstructural protein NS1, the partial nonstructural NS3 and NS4 proteins and the region of the partial 5'-end noncoding sequence. The cDNA fragments were cloned and sequenced. Sequence analysis of these clones showed that they share 83.7%, 93.2% and 93.6% similarity at the nucleotide level, and 86.6%, 94.1% and 92.9% homology at the amino acid level, with the previously published American, Japanese and Taiwanese isolates, respectively. Accordingly, the RNA genome we obtained is HCV type II, probably, the predominant subtype in Taiwan. PMID- 7866054 TI - Increased production of tumor necrosis factor-alpha and release of soluble CD4 and CD8 molecules, but decreased responsiveness to phytohemagglutinin in patients with nasopharyngeal carcinoma. AB - Twelve patients with nasopharyngeal carcinoma (NPC) were studied for spontaneous and phytohemagglutin (PHA)-stimulated production of cytokines, soluble markers and [3H] thymidine incorporation by mononuclear cells. The same number of patients with skin cancer and healthy subjects were used as control groups. Our results showed that the NPC group produced much more tumor necrosis factor-alpha (TNF alpha), soluble CD4 (sCD4) and CD8 (sCD8) in PHA-stimulated mononuclear cell supernatants than those in the other two groups. The levels of soluble interleukin-2 receptor (sIL-2R) and gamma-interferon (IFN gamma) in PHA stimulated supernatants were at the same high level in the NPC and healthy subjects groups while the concentrations were much lower in the skin cancer group. We also noticed that the early stage group in NPC patients had higher levels of interleukin-1 alpha (IL-1 alpha), TNF alpha, IFN gamma and sIL-2R in both spontaneous and PHA-stimulated mononuclear cell supernatants. The stimulation index of PHA-responsiveness was 155, 5.2 and 37, respectively, in the healthy subjects, skin cancer and NPC groups. The PHA-responsiveness was depressed in both the NPC and skin cancer groups. It seems that cancer patients have an impaired T cell mitogenic response after mitogen stimulation. NPC patients had better immune response than skin cancer patients in immune factor release or PHA-responsiveness. PMID- 7866055 TI - Blood pressure, circulating atrial natriuretic peptide and sodium excretion responses during acute saline infusion in patients with essential hypertension. AB - In order to examine whether changes in circulating atrial natriuretic peptide (ANP) and sodium excretion during saline infusion in patients with essential hypertension (EH) could be modulated by the severity of resting arterial blood pressure (BP), 30 subjects with EH and nine normotensive subjects were given 2 L of isotonic saline infusion at a rate of 500 mL/hour. Plasma ANP concentrations in EH increased significantly from 64.9 +/- 5.1 (mean +/- SEM) to 92.5 +/- 12.8 pg/mL at the first hour and peaked at the second hour. In normotensives, the increase of plasma ANP was not significant until the fourth hour of infusion. Hypertensive subjects sustained a greater percentage increment of mean BP (MBP) than normotensives at the end of infusion. Those with pre-saline MBP exceeding 107 mmHg (group A) exhibited a faster and greater rise in plasma ANP after saline loading than those having less than or equal to 107 mmHg (group B). The post saline four-hour natriuresis was appreciably higher in group A than group B, while the percentage increment of MBP at the fourth hour was significantly greater in the latter as compared to normal controls. These results indicate that patients with higher basal arterial pressure attain a faster and greater ANP response following saline infusion than those with lower BP. This phenomenon may be responsible for the maintenance of short-term fluid-volume and BP homeostasis during acute sodium loading in established EH. PMID- 7866056 TI - Correlates and predictive models for blood pressure values in residents of two communities in Taiwan. AB - Factors predicting systolic blood pressure (SBP) and diastolic blood pressure (DBP) were extensively studied in residents aged 18 years and above from 10 villages in two Taiwanese communities. In women, the associated factors identified included age, body mass index, waist/hip ratio (not selected as a factor for DBP), plasma uric acid, plasma chloride, urinary sodium/creatinine ratio, urinary calcium/creatinine ratio, education level, ancestral origin, parental hypertension status, and marital status. In men, the factors were age, body mass index, plasma triglyceride concentration, urinary sodium/creatinine ratio, smoking status, alcohol drinking status, parental hypertension status (not selected for DBP), and marital status (not selected for DBP). The degree of BP variation which could be significantly explained by the measured factors differed between SBP and DBP, and differed between men and women: 18% in men and 39% in women for SBP variation; 15% in men and 27% in women for DBP variation. Factors other than those included in the models should be explored, particularly for men. This study identifies, for Chinese populations, predictive factors of BP well known in Western societies (BMI, urinary sodium, plasma uric acid, alcohol consumption) and factors less emphasized in other studies (plasma triglyceride and marital status). A positive association between BP and urinary Na, a lack of association between BP and urinary K, and opposite findings in the relationship between BP and the education level for men (positive relation) and women (negative relation) are worth noting. PMID- 7866057 TI - Effect of EGb 761, a ginkgo biloba extract, on early arrhythmia induced by coronary occlusion and reperfusion in dogs. AB - EGb 761 is a preparation of Ginkgo biloba extract, which has complex biologic actions including free radical scavenging activity. To examine the anti arrhythmic effect of EGb 761, a canine preparation of coronary artery occlusion reperfusion was tested. Under intravenous anesthesia and open chest conditions, 32 dogs were subjected to 30 min of coronary occlusion, followed by reperfusion. Twelve received EGb 761 by intravenous injection, 1 mg/kg five minutes before coronary occlusion, followed by a continuous infusion of 0.1 mg/kg/min until five minutes after reperfusion. Immediately prior to reperfusion, an additional bolus dose of EGb 761 (1 mg/kg) was again injected (group A). The remaining 20 dogs received saline injection, and served as the control (group B). The electrocardiographic changes were recorded during the whole experimental course. The results showed that, during coronary occlusion, group A dogs had a lower count of ventricular premature beats than group B dogs. However, there was no difference in the incidence of ventricular tachycardia (VT) between the two groups. The duration of VT of the treated dogs was similar to that of the control dogs. The incidence of ventricular fibrillation (VF) was also similar. Upon reperfusion, the treated dogs were shown to be protected from VF. The duration of VT was also shorter in the treated group, although the incidence of VT was not different between the two groups. EGb 761 is effective in preventing early VF induced by coronary reperfusion while ineffective in protecting the ischemic VT and VF. PMID- 7866058 TI - Pre-discharge atrial pacing test in evaluation of risk stratification after uncomplicated myocardial infarction. AB - Right atrial pacing (RAP) using three pacing stages (I: 100 BPM/5 min; II: 120 BPM/5 min; III: 140 BPM/5 min) was performed for residual myocardial ischemia, hypotensive response and related prognostic significance in 55 uncomplicated acute myocardial infarction (AMI) patients. We aimed to clarify whether early risk stratification and jeopardized myocardium score, calculated using pacing results, could predict disease severity and future major cardiac events during long-term follow-up. During RAP testing, 24 patients displayed negative and 31 patients positive RAP. The positive RAP group had a significantly higher incidence of multivessel disease, higher jeopardized myocardium scores and left ventricular end-diastolic pressure than the negative RAP group. As expected, according to pacing response the disease severity score also showed a significant difference. During the one-year follow-up, there were three recurrent angina attacks, reinfarction and two congestive heart failures in the negative RAP group. In the positive RAP group, four died, six had new or recurrent myocardial infarctions and six developed congestive heart failure. Only six patients in the positive RAP group carried the critical risk, four suffered from recurrent angina, two developed reinfarction, three developed congestive heart failure, and two died. Total major cardiac events in the positive RAP group appeared to significantly increase compared to those in the negative RAP group. Our results show that early RAP with three pacing stages is useful in predicting subsequent major cardiac events after uncomplicated myocardial infarction. We also observed that hypotensive response during positive RAP represents the best predictor of critical risk requiring further invasive studies. We believe that RAP is justified for risk strategy. PMID- 7866059 TI - Rod cell activity in retinal degenerative rats. AB - The Royal College of Surgeons (RCS) rat is a good model for the study of the early onset of retinal degenerative disorders. RCS retinal disease is often associated with the loss of rhodopsin in outer segment membranes and the progressive degeneration of photoreceptor cells. This study was conducted to investigate the possible mechanisms of the loss of photoreceptor sensitivity. The electroretinographic responses were recorded in RCS and control rats, age 15, 25 and 35 days, as well as in adult control rats. The a-waves were analyzed using the Hood and Birch model of activation of photoresponse. Photoresponse latency in the RCS rats was prolonged as the disease progressed. The maximum recorded a-wave amplitudes were significantly lower for the RCS rats compared to the control rats. The sensitivity of a-waves as indicated by Ka, the semi-saturation constant, varied and depended on the age of the rats and degenerative stage of the disease. The model's time to peak response increased more than twofold as the degeneration advanced. The changes in a-waves indicate that RCS disease causes progressive impairment of the rod photoresponse. It also suggests that in addition to the phagocytic defect of the retinal pigment epithelium, the abnormal composition of the membrane lipids and the interphotoreceptor matrix and the rhodopsin loss may also cause abnormal photoresponses in RCS rats. PMID- 7866060 TI - Ileal neobladder reconstruction after radical cystoprostatectomy. AB - To improve the outcome and patient acceptance of bladder substitution, five male patients underwent O-shaped ileal neobladder reconstruction, after radical cystoprostatectomy for invasive bladder cancer, with a mean follow-up of 11 months. With only 40 cm of ileal segment, an O-shaped neobladder was constructed after complete detubularization. Bilateral ureters were implanted using the Le Duc-Camey method. Six months after operation, all patients were totally continent during the day time, and one patient suffered from mild incontinence at night, which could be overcome by waking to void once or twice. The satisfactory continence levels are in agreement with a urodynamic study of the neobladder which showed a low pressure, high-capacity (mean, 456 mL) reservoir in the cystometric tracings. The mean maximal flow rate was 22.2 mL/sec, the mean residual urine was minimal (10 to 20 mL), the mean maximal urethral closing pressure was 74.4 cm H2O and the mean functional profile length was 2.9 cm. All renal units do not have neovesico-ureteral reflux. Two patients showed unilateral hydronephrosis which subsided later, one patient sustained bilateral hydronephrosis and died of jejunal perforation five months postoperatively. There were few perioperative complications and no patient expressed regret at having undergone the procedure. We consider bladder substitution to be the treatment of choice in male patients requiring radical cystoprostatectomy. PMID- 7866061 TI - Grip and pinch strength in Chinese adults and their relationship with anthropometric factors. AB - In this study, we evaluated the correlation of four types of hand strength (hand grip, tip pinch, palmar pinch and key pinch) with age, sex, body weight, body height, body mass index, triceps skinfold thickness, mid-arm circumference and mid-forearm circumference in a group of 437 Chinese adults (195 men and 242 women) who ranged in age from 28 to 78 years. All of the hand strengths studied correlated positively with gender, body weight, body height, mid-arm and mid forearm circumference and negatively with age and triceps skinfold thickness in the analyses of simple correlation coefficients. Men were found to be more powerful than women in all hand strength types in different age groups. The magnitude of strength decline with age was more prominent in grip strength than pinch strength including palmar, tip and key. Stepwise multiple regression analyses showed that sex, age and mid-forearm circumference were most predictive of all types of hand strength. Body height was an additional independent predictor of grip and palmar pinch. Body mass index, body weight, mid-arm circumference and triceps skinfold thickness were not independent predictors associated with hand strength. PMID- 7866062 TI - Vibration arthrometry of the knee with torn meniscus: a preliminary report. AB - Although projects using vibration signals generated by the joint to detect joint disorders are still experimental, vibration arthrometry has been shown to be useful in assessing meniscal pathology. A prospective study using vibration arthrometry to diagnose meniscal tears was carried out in 25 consecutive patients with knee injuries. They comprised 20 males and five females with an average age of 34 years. An arthroscopic examination of the injured knee was given to every patient. Six cases of medial meniscal tear, 12 lateral meniscal tear, and two torn discoid menisci were found. The remaining five cases had normal menisci. By correlating the vibration arthrography of the patients to their corresponding arthroscopic findings, 15 were found to be true-positive, five true-negative and five false-negative. There were no false-positive readings. The accuracy, sensitivity and specificity of the vibration arthrometry in diagnosing meniscal tear was 80%, 75% and 100%, respectively. Vibration arthrometry was shown to be a reliable, non-invasive diagnostic tool in diagnosing meniscal tear of the knee. PMID- 7866063 TI - Prenatal diagnosis of dicephalic conjoined twins: report of a case. AB - Dicephalus is one of the rarest types of conjoined twins. In such cases, the twins are usually stillborn or die shortly after birth. Termination of the pregnancy is recommended if conjoined twins are diagnosed early in the second trimester. A case of dicephalic conjoined twins with cystic hygroma diagnosed prenatally by ultrasound at 16 weeks' gestation is presented. The ultrasonographic findings, management and pathology are discussed. PMID- 7866064 TI - Cardiovascular collapse during gynecologic laparoscopy complicated by pulmonary edema: report of a case. AB - Although gynecologic laparoscopic surgery has recently become a routine and widespread operative procedure in Taiwan, the potential risks and complications in the clinical practice of laparoscopy should not be overlooked. Whilst the incidence of complications are rare, they can sometimes be serious, even life threatening. This case report presents a woman with ruptured endometrioma, who developed sudden-onset cardiovascular collapse during laparoscopic procedure, in which carbon dioxide was used for insufflation. After resuscitation including cardioversion, her vital functions were restored; pulmonary edema developed soon afterwards but was resolved with conservative treatment. We discuss the possible causes of cardiovascular collapse during laparoscopic procedure and the management of resulting complications. PMID- 7866065 TI - Fibrous dysplasia of the rib presenting as a huge chest wall tumor: report of a case. AB - Fibrous dysplasia of the rib is not uncommon, but is rarely demonstrated as a huge chest wall mass with severe clinical symptoms. A 59-year-old patient, presenting with a huge, rapidly expanding chest wall tumor compressing the lung, liver and heart accompanied by chest pain and dyspnea, is reported. The tumor was success-fully excised by local radical resection. PMID- 7866066 TI - Pure cheiro-oral syndrome due to a small pontine hematoma: report of a case and review of the literature. AB - Cheiro-oral syndrome is frequently associated with other neurologic deficits; its pure form is rare. We report a 60-year-old man with pure cheiro-oral syndrome due to a small hematoma located in the ventral tegmentum of the right upper pons. His sensory disturbance remained unchanged during a follow-up period of 16 months. Review of the literature suggests that the pons is the most frequent site of lesions in pure cheiro-oral syndrome. PMID- 7866067 TI - Scrotal migration of a ventriculo-peritoneal shunt: report of a case. AB - A seven-month-old male infant developed a hydrocele four weeks after the surgical insertion of a ventriculo-peritoneal shunt. The shunt tip in the scrotum was palpable, visible on transillumination, and evident on abdominal X ray. The hydrocele persisted after the surgical repositioning of the shunt tip via a reopening of the abdominal wound. The shunt tip returned to the scrotum one week later, supporting the theory that a flow of cerebrospinal fluid into the patent processus vaginalis creates a trough effect, thus drawing the mobile shunt tip into the center of the trough. After an inguinal herniotomy and the reduction of the shunt tip, the hydrocele subsided. PMID- 7866068 TI - Azithromycin in the treatment of pneumonia caused by Chlamydia pneumoniae: report of a case. AB - We report a 67-year-old male with pneumonia in which Chlamydia pneumoniae was identified by serologic studies as the causative agent. After initial treatment failure with amoxicillin + clavulanic acid, pneumonia was successfully treated with the administration of oral azithromycin, 500 mg per day, for three days. Azithromycin is a new macrolide which has a long half-life and superior action to erythromycin. It provides a new and alternative choice in the treatment of Chlamydia pneumoniae infection in the future. PMID- 7866069 TI - Rhodotorula septicemia: report of a case. AB - With the increased use of central venous catheters in cancer patients, there has been an increase in the recovery of environmental and skin organisms from blood cultures. A red yeast, Rhodotorula, an infrequent cause of infection in humans, was isolated from a patient with acute myeloblastic leukemia undergoing bone marrow transplant while he received parenteral nutritional fluids by an indwelling catheter. The patient was clinically ill, as manifested by fever and chills. The patient was treated with amphotericin B and the catheter was removed. He survived the fungemic episode with no recurrence of fungal infection. PMID- 7866071 TI - Finding a way through the cost and benefit maze. PMID- 7866070 TI - Tamoxifen and the uterus. PMID- 7866072 TI - Changes in semen and the testis. PMID- 7866073 TI - European directive on training for general practice. PMID- 7866074 TI - Should doctors charge doctors for medical services? PMID- 7866075 TI - Scottish private hospital calls in receivers. PMID- 7866076 TI - Chernobyl damaged health, says study. PMID- 7866077 TI - Victims of Creutzfeldt-Jakob disease prompt code of conduct. PMID- 7866078 TI - Focus: Washington. A new season for health reform. PMID- 7866079 TI - Antibody to herpes simplex virus type 2 as serological marker of sexual lifestyle in populations. AB - OBJECTIVES: To examine the epidemiology of antibody to herpes simplex virus type 2 and to assess its suitability as a serological marker of sexual behaviour in populations with high and low prevalences. DESIGN: Cross sectional survey. SETTING: Department of genitourinary medicine and blood donation centre in central London. SUBJECTS: Representative sample of 869 patients attending department between November 1990 and December 1991, and 1494 consecutive blood donors attending for donation between February and April 1992. METHOD: Participants had a blood sample taken for antibody testing with a novel type specific assay and completed a questionnaire. RESULTS: Prevalence of antibody differed significantly between the two groups (188/833 (22.7%) clinic attenders; 102/1347 (7.6%) blood donors). In both populations antibody was strongly associated with sex, sexual orientation, years of sexual activity, number of lifetime sexual partners, and past infection with sexually transmitted diseases after other factors were controlled for. Only 130 (45%) of all those with antibody had symptoms suggestive of genital herpes, and 79 (27.4%) had had genital herpes diagnosed. Of those without antibody to herpes simplex viruses type 1 and 2, 8.0% reported genital blisters or sores and 1.1% had had genital herpes diagnosed by a doctor. CONCLUSIONS: The strong relation between herpes simplex virus type 2 and sexual lifestyle suggests that the presence of antibody to the virus may be suitable for use as an objective, serological marker of patterns of sexual behaviour in different populations. These data show that only a minority of those infected with herpes simplex virus type 2 have a diagnosis of genital herpes or express clinical symptoms, making serological determinants of infection essential for epidemiological studies. PMID- 7866080 TI - Effect of homoeopathic medicines on daily burden of symptoms in children with recurrent upper respiratory tract infections. AB - OBJECTIVE: To investigate the intrinsic effects of individually prescribed homoeopathic medicines. DESIGN: Randomised double blind placebo controlled study. SETTING: Paediatric outpatient department of university hospital. PATIENTS: 175 children with frequently recurring upper respiratory tract infections. Of the 170 children evaluable, 86 were randomised to homoeopathic medicines (47 boys, 39 girls; median age at start 4.2 years; median number of episodes in past year 4) and 84 to placebo (43 boys, 41 girls; median age at start 3.6 years; median number of episodes in past year 4). MAIN OUTCOME MEASURES: Mean score for daily symptoms, number of antibiotic courses, and number of adenoidectomies and tonsillectomies over one year of follow up. RESULTS: The mean daily symptom score was 2.61 in the placebo group and 2.21 in the treatment group (difference 0.41; 95% confidence interval -0.02 to 0.83). In both groups the use of antibiotics was greatly reduced compared with that in the year before entering the trial (from 73 to 33 in the treatment group and from 69 to 43 in the placebo group). The proportion of children in the treatment group having adenoidectomies was lower in the treatment group (16%, 8/50) than in the placebo group (21%, 9/42). The proportion having tonsillectomies was the same in both groups (5%). CONCLUSION: Individually prescribed homoeopathic medicines seem to add little to careful counselling of children with recurrent upper respiratory tract infection in reducing the daily burden of symptoms, use of antibiotics, and need for adenoidectomy and tonsillectomy. PMID- 7866081 TI - Educational status, coronary heart disease, and coronary risk factor prevalence in a rural population of India. AB - OBJECTIVE: To define the association between educational level and prevalence of coronary heart disease and coronary risk factors in India. DESIGN: Total community cross sectional survey with a doctor administered questionnaire, physical examination, and electrocardiography. SETTING: A cluster of three villages in rural Rajasthan, western India. SUBJECTS: 3148 residents aged over 20 (1982 men, 1166 women) divided into various groups according to years of formal schooling. RESULTS: Illiteracy and low educational levels were associated with less prestigious occupations (agricultural and farm labouring) and inferior housing. There was an inverse correlation of educational level with age (rank correlation: mean -0.45, women -0.49). The prevalence of coronary heart disease (diagnosed by electrocardiography) was significantly higher among uneducated and less educated people and showed an inverse relation with education in both sexes. Among uneducated and less educated people there was a higher prevalence of the coronary risk factors smoking and hypertension. Educational level showed a significant inverse correlation with systolic and diastolic blood pressure. Logistic regression analysis with adjustment for age showed that educational level had an inverse relation with prevalence of electrocardiographically diagnosed coronary heart disease (odds ratio: men 0.82, women 0.53), hypertension (men 0.88, women 0.56), and smoking (men 0.73, women 0.65) but not with hypercholesterolaemia and obesity. The inverse relation of coronary heart disease with educational level abated after adjustment for smoking, physical activity, body mass index, and blood pressure (odds ratio: men 0.98, women 0.78). CONCLUSION: Uneducated and less educated people in rural India have a higher prevalence of coronary heart disease and of the coronary risk factors smoking and hypertension. PMID- 7866082 TI - Study of erythropoietin in treatment of anaemia in patients with rheumatoid arthritis. PMID- 7866083 TI - Implementation of government recommendations for immunising infants at risk of hepatitis B. PMID- 7866085 TI - Why sources of heterogeneity in meta-analysis should be investigated. AB - Although meta-analysis is now well established as a method of reviewing evidence, an uncritical use of the technique can be very misleading. One common problem is the failure to investigate appropriately the sources of heterogeneity, in particular the clinical differences between the studies included. This paper distinguishes between the concepts of clinical and statistical heterogeneity and exemplifies the importance of investigating heterogeneity by using published meta analyses of epidemiological studies of serum cholesterol concentration and clinical trials of its reduction. Although not without some dangers of speculative conclusions, prompted by overzealous inspection of the data to hand, a sensible investigation of sources of heterogeneity should increase both the scientific and the clinical relevance of the results of meta-analyses. PMID- 7866084 TI - Cardiology--I: Treatment of myocardial infarction, unstable angina, and angina pectoris. PMID- 7866086 TI - Is stroke better managed in the community? Community care allows patients to reach their full potential. PMID- 7866087 TI - Is stroke better managed in the community? Only hospitals can provide the required skills. PMID- 7866088 TI - Electronic health records: the European scene. AB - Caring for patients' health problems relies increasingly on sharing information between clinical departments and disciplines and with managers. The medical record of the future will need to provide a flexible and shareable framework for recording and analysing the consultation process. The advanced informatics in medicine (AIM) programme seeks to encourage research and development in telemedicine in areas that are beyond the scope of any one country. It includes many European projects attempting to define the best storage and transmission formats for such diverse data types as laboratory results, biosignals, x ray images, and photographs, and in clinical specialties varying from intensive care to medicine for elderly people. One example, the good European health record project, is developing a model architecture for computerised health records across Europe that is capable of operating on a wide variety of computer hardwares and will also be able to communicate with many different information systems. The ultimate European health record will be comprehensive and medicolegally acceptable across clinical domains, hold all data types, and be automatically translated between languages. PMID- 7866089 TI - Acute swollen legs due to rhabdomyolysis: initial management as deep vein thrombosis may lead to acute renal failure. PMID- 7866090 TI - ABC of breast diseases. Role of systemic treatment for primary operable breast cancer. PMID- 7866091 TI - Infectivity of pneumonic plague. PMID- 7866092 TI - Plague in India. PMID- 7866093 TI - The sight test fee. Little evidence to support conclusions. PMID- 7866094 TI - The sight test fee. Need for more cautious analysis. PMID- 7866095 TI - The sight test fee. Potential to spread alarm. PMID- 7866096 TI - The sight test fee. 1988 data may be misleading. PMID- 7866097 TI - The sight test fee. Relatives at risk can have free test. PMID- 7866098 TI - The sight test fee. Similar experience in Leeds. PMID- 7866099 TI - The sight test fee. Abolish charges for elderly people. PMID- 7866100 TI - The sight test fee. Optometrists are making more thoughtful referrals. PMID- 7866101 TI - The sight test fee. Many people cannot afford to pay fees for NHS services. PMID- 7866102 TI - Serum screening for Down's syndrome. National policy would ensure consistency. PMID- 7866103 TI - Serum screening for Down's syndrome. Counselling should emphasise possible outcomes of screening. PMID- 7866104 TI - Serum screening for Down's syndrome. Keeping the concept of risk simple. PMID- 7866105 TI - Screening for secondary causes of hyperlipidaemia in general practice. Correct diagnosis needs to be established. PMID- 7866106 TI - Screening for secondary causes of hyperlipidaemia in general practice. Misdiagnosis may result in litigation. PMID- 7866107 TI - Screening for secondary causes of hyperlipidaemia in general practice. Assess against well recognised criteria. PMID- 7866108 TI - Diabetes in the developing world. PMID- 7866109 TI - Purchasing vascular services. Centralisation could result in two tier service. PMID- 7866110 TI - Purchasing vascular services. Looking after one's own? PMID- 7866111 TI - What should be done about interval breast cancers? PMID- 7866112 TI - What general practitioners should do about breast screening. PMID- 7866113 TI - Suicide and antidepressants. PMID- 7866114 TI - Unlinked anonymous HIV screening programme in England and Wales. PMID- 7866115 TI - Health care: what's science got to do with it? PMID- 7866116 TI - Manchester tackles failure rate of Asian students. PMID- 7866117 TI - Crocodiles help to develop artificial blood. PMID- 7866118 TI - Childbirth trust calls for rights to home births. PMID- 7866119 TI - Israel introduces national health insurance system. PMID- 7866120 TI - HIV infection concentrated in London. PMID- 7866121 TI - Europe cautious over genetics trials. PMID- 7866122 TI - Relative toxicity of benzodiazepines in overdose. AB - OBJECTIVE: To assess the sedative effects in overdose of temazepam and oxazepam compared with other benzodiazepines to determine if this explains reported differences in fatal toxicity. DESIGN: Cohort study of patients admitted with benzodiazepine poisoning. SETTING: Newcastle, Australia. SUBJECTS: 303 patients who had ingested benzodiazepine alone or in combination with alcohol and presented to a general hospital which served a well defined geographical area. MAIN OUTCOME MEASURES: Degree of sedation: Glasgow coma score, McCarron Score, and whether patients were stuporose or comatose. RESULTS: Oxazepam produced less and temazepam more sedation than other benzodiazepines. Unadjusted odds ratios for coma with oxazepam and temazepam compared with other benzodiazepines were 0.0 (95% confidence interval 0.0 to 0.85) and 1.86 (0.68 to 4.77) respectively, chi 2 = 7.08, 2df, P = 0.03. After adjustment for potentially confounding effects of age, dose ingested, and coingestion of alcohol, the odds ratios were 0.22 (0.0 to 1.43) for oxazepam and 1.94 (0.57 to 6.23) for temazepam. Similar results were obtained for other measures of sedation. CONCLUSIONS: These results were in accordance with fatal toxicity indices derived from coroners' data on mortality and rates of prescription. The relative safety of benzodiazepines in overdose should be a consideration when they are prescribed. PMID- 7866123 TI - Relative mortality from overdose of antidepressants. AB - OBJECTIVE: To compare the fatal toxicities of antidepressant drugs in 1987-92. DESIGN: Retrospective epidemiological review of prescription data of the Department of Health, Scottish Office Home and Health Department, and Welsh Health Common Services Authority (excluding data from most private general practices and most hospitals), and mortality data from the Office of Population Censuses and Surveys and General Register Office in Scotland. SETTING: General practice, England, Scotland, and Wales. MAIN OUTCOME MEASURES: Deaths per million prescriptions and deaths per defined daily dose. RESULTS: 81.6% (1310/1606) of deaths from antidepressant overdose were due to two drugs, amitriptyline and dothiepin. The overall average of deaths per million prescriptions was 30.1. The overall rate for tricyclic drugs was 34.14 (95% confidence interval 32.47 to 38.86; P < 0.001), monoamine oxidase inhibitors 13.48 (6.93 to 22.19; P < 0.001), atypical drugs 6.19 (4.04 to 8.80; P < 0.001), and selective serotonin reuptake inhibitors 2.02 (0.64 to 4.17; P < 0.001). The numbers of deaths per million prescriptions of amoxapine, dothiepin, and amitriptyline were significantly higher than expected, while nine drugs had a significantly lower number of deaths per million prescriptions than expected. Analysis of deaths per defined daily dose showed a similar pattern. CONCLUSIONS: Safety in overdose should be considered in risk-benefit and cost-benefit considerations of antidepressants. A switch in prescribing, from drugs with a high number of deaths per million prescriptions to drugs with a low number, could reduce the numbers of deaths from overdose. Although this form of suicide prevention can be implemented easily and immediately, its introduction needs to be considered against the higher costs of some of the newer drugs. PMID- 7866124 TI - Is the three year breast screening interval too long? Occurrence of interval cancers in NHS breast screening programme's north western region. AB - OBJECTIVE: To report the detection rate of interval cancers in women screened by the NHS breast screening programme. DESIGN: Detection of interval cancers by computer linkage of records held by the screening centres in the North Western Regional Health Authority with breast cancer registrations at the regional cancer registry. SETTING: North Western Regional Health Authority. SUBJECTS: 137,421 women screened between 1 March 1988 and 31 March 1992 who had a negative screening result. RESULTS: 297 invasive interval cancers were detected. The rate of detection of interval cancers expressed as a proportion of the underlying incidence was 31% in the first 12 months after screening, 52% between 12 and 24 months, and 82% between 24 and 36 months. CONCLUSION: The incidence of interval cancers in the third year after breast screening approaches that which would have been expected in the absence of screening and suggests that the three year interval between screens is too long. PMID- 7866125 TI - Parental refusal to have children immunised: extent and reasons. PMID- 7866126 TI - Eating habits and attitudes among mothers of children with feeding disorders. PMID- 7866127 TI - Comparison of uptake of breast screening, cervical screening, and childhood immunisation. PMID- 7866128 TI - General practitioners' knowledge and use of living wills. PMID- 7866129 TI - Purchaser-provider: the international dimension. AB - Purchaser-provider systems in health care are being implemented in several countries and are under consideration in many more. These new arrangements are described for the United Kingdom, Finland, New Zealand, and Australia, and in each case responsibility for funding, purchasing, providing, and ownership is identified. The four systems, along with managed care organisations in the United States, are also compared with regard to several important features. There is a fundamental similarity between these purchaser-provider arrangements but several key differences are well worth systematic study. This is a major challenge for academic bodies in Britain and other countries, and the opportunity to learn from each other should not be missed. PMID- 7866130 TI - Making an advance directive. AB - The introduction in Britain of advance directives--which allow a person to state in advance of becoming incompetent that they wish to take part in treatment decisions when no longer mentally competent--has now been advocated by the medical and legal establishments. The practical application of directives relating to health care would be simplified by the adoption of a standard model document together with guidelines summarising the background clinical conditions and any subsequent acute events that may make it appropriate to trigger the use of a directive. As no specific legislation exists, good communication is needed at the various stages between the drafting and implementation of directives if the system of directives is to be successful. PMID- 7866131 TI - ABC of rheumatology. Pain in the hand and wrist. PMID- 7866132 TI - Making finance work for you--strategic issues in clinical directorates. PMID- 7866133 TI - Chemotherapy for solid tumours. Routine treatment not yet justified. PMID- 7866134 TI - Important progress in treatment. Chemotherapy for solid tumours. PMID- 7866135 TI - How to do it. Participate in an international conference. AB - Attending an international conference should be instructive and fun. But it can also be alarming and lonely. Although participating in scientific conferences is now almost essential to medical career development, no medical school describes how to make the most of the opportunity as part of its curriculum. Here are some hints on how to get yourself organised so that the experience can be both scientifically productive and enjoyable. In essence, you should travel, see places, meet people, make friends, and identify one or two ideas that you can apply in your own work or research. PMID- 7866136 TI - Treating asthma. Clinical efficacy and safety of generic inhalers is well established. PMID- 7866137 TI - Treating asthma. Prescription Pricing Authority aims to promote high quality prescribing. PMID- 7866138 TI - Treating asthma. Beta agonists are widely used. PMID- 7866139 TI - Treating asthma. Scoring system developed for drug related morbidity. PMID- 7866140 TI - Simple aspiration for spontaneous pneumothorax. Authors reinvent the wheel. PMID- 7866141 TI - Enteroviral hypothesis for motor neurone disease. PMID- 7866142 TI - Simple aspiration for spontaneous pneumothorax. May not reduce the need for pleurectomy. PMID- 7866143 TI - Homoeopathy for recurrent upper respiratory tract infections. Use of daily symptom score not validated. PMID- 7866144 TI - Homoeopathy for recurrent upper respiratory tract infections. Power of study was not estimated. PMID- 7866145 TI - The health of leaders. Should they have occupational health screening? PMID- 7866146 TI - Use of personal records for research purposes. Identification numbers help maintain confidentiality. PMID- 7866147 TI - Use of personal records for research purposes. Guidelines may affect audit. PMID- 7866148 TI - Use of personal records for research purposes. Records prematurely destroyed. PMID- 7866149 TI - Use of personal records for research purposes. Restrictions unnecessary and obstructive. PMID- 7866151 TI - Circumcision. PMID- 7866150 TI - Psychotic illness in ethnic groups. Conclusions of study are unwarranted. PMID- 7866152 TI - Social observations on childhood. PMID- 7866153 TI - Triglyceride concentration and coronary heart disease. PMID- 7866154 TI - Hepatitis C in asymptomatic blood donors. Did ethics committee approve study? PMID- 7866155 TI - Intrahepatic cholestasis of pregnancy. PMID- 7866156 TI - Certifying incapacity for work. PMID- 7866157 TI - Infectivity of pneumonic plague. PMID- 7866158 TI - Ethics of rationing health care services. PMID- 7866159 TI - Careers in academic general practice. PMID- 7866160 TI - Electronic health records. PMID- 7866161 TI - Out of hours care. Cultural change is necessary. PMID- 7866162 TI - Out of hours care. Establish primary care centres in hospitals. PMID- 7866163 TI - Preventing crime and violence. PMID- 7866164 TI - Television violence and children. PMID- 7866165 TI - Bullying in schools: doctors' responsibilities. PMID- 7866167 TI - Emergency delays need urgent attention. PMID- 7866166 TI - Imprisonment, injecting drug use, and bloodborne viruses. PMID- 7866168 TI - Spread of bloodborne viruses among Australian prison entrants. AB - OBJECTIVES: To assess spread of bloodborne viruses among prison entrants in Victoria, Australia. DESIGN: Voluntary confidential testing of all prison entrants for markers of exposure to bloodborne viruses with collection of minimal data on demography and risk factors over 12 months. SETTING: Her Majesty's Prisons, Pentridge and Fairlea, Victoria, Australia. SUBJECTS: 3429 male and 198 female prison entrants (> 99% of all prison entrants); 344 entered prison and were tested more than once. MAIN OUTCOME MEASURES: Prevalence and incidence of antibodies to HIV, hepatitis B, and hepatitis C viruses, and minimal data on risk factors. RESULTS: 1562 (46%) gave a history of use of injected drugs, 1171 (33%) had antibody to hepatitis B core antigen, 1418 (39%) were anti-hepatitis C positive including 914 (64%) of the men who injected drugs, 91 (2.5%) were positive for hepatitis B surface antigen, and 17 (0.47%) were positive for antibody to HIV. Incidence rates for infection with hepatitis B and C virus were 12.6 and 18.3 per 100 person years, respectively; in men who injected drugs and were aged less than 30 years (29% of all prison entrants) these were 21 and 41 per 100 person years. Seroconversion to hepatitis B or C was associated with young age and shorter stay in prison. Only 5% of those who were not immune to hepatitis B reported hepatitis B immunisation. CONCLUSIONS: Hepatitis B and C are spreading rapidly through some populations of injecting drug users in Victoria, particularly among men aged less than 30 years at risk of imprisonment in whom rates of spread are extreme; this group constitutes a sizeable at risk population for spread of HIV. This spread is occurring in a context of integrated harm reduction measures outside prisons for prevention of viral spread but few programmes within or on transition from prisons; it poses an urgent challenge to these programmes. PMID- 7866169 TI - Outbreak of HIV infection in a Scottish prison. AB - OBJECTIVE--To investigate the possible spread of HIV infection and its route of transmission among prison inmates. DESIGN--In response to an outbreak of acute clinical hepatitis B and two seroconversions to HIV infection, counselling and testing for HIV were offered to all inmates over a two week period in July 1993. Information was sought about drug injecting, sexual behaviour, and previous HIV testing. SETTING--HM Prison Glenochil in Scotland. SUBJECTS--Adult male prisoners. MAIN OUTCOME MEASURES--Uptake of HIV counselling and testing; occurrence and mode of HIV transmission within the prison. RESULTS--Of a total 378 inmates, 227 (60%) were counselled and 162 (43%) tested for HIV. Twelve (7%) of those tested were positive for antibody to HIV. One third (76) of those counselled had injected drugs at some time, of whom 33 (43%) had injected in Glenochil; all 12 seropositive men belonged to this latter group. Thirty two of these 33 had shared needles and syringes in the prison. A further two inmates who injected in the prison were diagnosed as positive for HIV two months previously. Evidence based on sequential results and time of entry into prison indicated that eight transmissions definitely occurred within prison in the first half of 1993. CONCLUSION--This is the first report of an outbreak of HIV infection occurring within a prison. Restricted access to injecting equipment resulted in random sharing and placed injectors at high risk of becoming infected with HIV. Measures to prevent further spread of infection among prison injectors are urgently required. PMID- 7866170 TI - Drug injection and HIV prevalence in inmates of Glenochil prison. AB - OBJECTIVE: To determine prevalence of HIV infection and drug injecting behaviour among inmates of Glenochil Prison on a specified date a year after an outbreak of hepatitis B and HIV infection. DESIGN: Cross sectional: voluntary, anonymous HIV salivary antibody surveillance and linked self completion questionnaire on risk factors. SETTING: Glenochil prison, Scotland, a year after an outbreak of hepatitis B and HIV transmission related to drug injection. SUBJECTS: 352 prisoners, of whom 295 (84%) took part; 284 questionnaires (96%) passed logical checks. MAIN OUTCOME MEASURES: HIV prevalence; proportion of all inmates who had ever injected drugs, had ever injected inside prison, had started injecting drugs while inside prison. RESULTS: More than half (150/284) the current inmates were also in Glenochil Prison during the critical period of January to June 1993, when hepatitis B and HIV were transmitted. Similar proportions of current inmates and men who were also in Glenochil during the critical period were drug users (27% (75/278) v 30% (44/149)). A quarter of injecting drug users (18/72) had first injected inside prison, irrespective of whether they were in Glenochil in January to June 1993 and regardless of the calendar period when they first injected. Significantly more inmates from Glasgow (41%; 56/138) than from Edinburgh (21%; 7/34) or elsewhere (11%; 12/106) were injecting drug users. On testing for HIV, seven saliva samples out of 293 gave positive results--four were presumed to be from inmates known to be infected with HIV, and the others from injecting drug users from Glasgow, all of whom had been in Glenochil during January to June 1993, when two of the three had injected drugs and had been tested for HIV, with negative results. The ratio of overall (2.4%) to disclosed (1.4%) HIV prevalence was 1.7. For men who had injected drugs in Glenochil during January to June 1993, HIV prevalence was estimated at 29%. CONCLUSION: Between a quarter and a third of prisoners who injected drugs in Glenochil in January to June 1993 were infected with HIV. There is widespread ongoing risk of bloodborne virus infection within prisons, which is probably long standing but demands urgent attention. PMID- 7866171 TI - Short stature and diabetic nephropathy. PMID- 7866172 TI - Statistics notes: the normal distribution. PMID- 7866173 TI - Natural course of 500 consecutive cases of whooping cough: a general practice population study. AB - OBJECTIVE: To describe the natural course of whooping cough. DESIGN: Observational study of a general practice population. SETTING: Discrete semirural East Midlands practice of 11,500 patients. SUBJECTS: 500 consecutive cases of whooping cough diagnosed clinically during 1977-92. MAIN OUTCOME MEASURES: Incidence of vomiting, whooping, apnoea, admission to hospital, and complications; duration and frequency of paroxysms. Pattern of spread. RESULTS: The incidence in the practice population was 4347/100,000 population compared with a notification rate for England and Wales of 717/100,000. Most cases were relatively mild. 284 patients vomited after paroxysms, 242 whooped, and 57 had apnoea. Duration and frequency of paroxysms varied widely. Female and unimmunised patients suffered more severe disease. Bordetella was isolated from fewer immunised patients (24/96 v 63/122 unimmunised). Infection was usually spread through contacts with someone with clinical whooping cough. Five patients developed pneumonia, three of whom had been immunised. Three patients required hospital admission. CONCLUSIONS: Most cases of whooping cough are relatively mild. Such cases are difficult to diagnose without a high index of suspicion because doctors are unlikely to hear the characteristic cough, which may be the only symptom. Parents can be reassured that a serious outcome is unlikely. Adults also get whooping cough, especially from their children, and get the same symptoms as children. The difficulty of early diagnosis and probability of missed cases reinforces the need to keep the incidence low through immunisation in order to protect infants, who are the most vulnerable. PMID- 7866174 TI - Lyme disease in the United Kingdom. PMID- 7866175 TI - Severe gastroparesis diabeticorum in a young patient with insulin dependent diabetes. PMID- 7866176 TI - Financial accounting in the NHS. PMID- 7866177 TI - Should carotid endarterectomy be purchased? Treatment avoids much morbidity. PMID- 7866178 TI - Should carotid endarterectomy be purchased? Purchasers need a broader perspective. PMID- 7866179 TI - ABC of rheumatology. Pain in the hip and knee. PMID- 7866180 TI - Mortality and alcohol consumption. Non-drinkers shouldn't be used as baseline. PMID- 7866181 TI - Length of femoral neck and rates of hip fractures. Measurements may not be reliable. PMID- 7866182 TI - Mortality and alcohol consumption. Moderate drinking also improves health. PMID- 7866183 TI - Mortality and alcohol consumption. The conclusions we draw. PMID- 7866184 TI - Severe chickenpox during treatment with corticosteroids. At what age should varicella-zoster immunoglobulin be given? PMID- 7866185 TI - Severe chickenpox during treatment with corticosteroids. Immunoglobulin should be given if steroid dosage was > or = 0.5 mg/kg/day in preceding three months. PMID- 7866186 TI - Severe chickenpox during treatment with corticosteroids. Latex assay shows false negatives. PMID- 7866187 TI - Confounding and Simpson's paradox. Multiple regression would confound the clinicians. PMID- 7866188 TI - Macroglossia. Classify the pathology as normal or abnormal. PMID- 7866189 TI - Macroglossia. Tracheostomy may not be necessary during surgery. PMID- 7866190 TI - Matching in case-control studies. PMID- 7866191 TI - Numbers alone cannot determine rational treatment. PMID- 7866192 TI - Positive predictive value of tests for breast disease. PMID- 7866193 TI - Referral of women with breast lumps. PMID- 7866194 TI - Psychotic illness in ethnic groups. Data on Surinamese patients in The Netherlands support study results. PMID- 7866195 TI - Psychotic illness in ethnic groups. Numbers are small. PMID- 7866196 TI - Psychotic illness in ethnic groups. Study did not deal with "category fallacy". PMID- 7866197 TI - Psychotic illness in ethnic groups. Biological is not synonymous with genetic. PMID- 7866198 TI - Psychotic illness in ethnic groups. Census categories of ethnic group are limited. PMID- 7866199 TI - Psychotic illness in ethnic groups. Some ethnic groups may be more vulnerable to extremes of social deprivation. PMID- 7866200 TI - Psychotic illness in ethnic groups. Larger studies are needed. PMID- 7866201 TI - The persistent vegetative state. PMID- 7866202 TI - Rethinking sexual health clinics. PMID- 7866203 TI - Learning medicine in the community. PMID- 7866204 TI - The shaken infant syndrome. PMID- 7866205 TI - New treatments for multiple sclerosis. PMID- 7866206 TI - Turkish doctors tackle human rights crisis. PMID- 7866207 TI - Egyptian doctors' arrest sparks protest. PMID- 7866208 TI - Report highlights needs of minority groups. PMID- 7866210 TI - Doctor in Zimbabwe race row out on bail. PMID- 7866209 TI - Smokers in Britain get legal aid. PMID- 7866211 TI - Israel compensates for ringworm treatment. PMID- 7866212 TI - US announces drug treatment for sickle cell anaemia. PMID- 7866214 TI - Serum cholesterol concentration and risk of brain cancer. PMID- 7866213 TI - Antenatal screening for carriers of cystic fibrosis: randomised trial of stepwise v couple screening. AB - OBJECTIVE: To perform a rigorous comparative evaluation of stepwise and couple approaches to antenatal carrier screening for cystic fibrosis. DESIGN: Pragmatic randomised trial. SETTING: Hospital antenatal clinic serving a regional population. SUBJECTS: 2002 women (couples) attending for booking antenatal visit at less than 17 weeks' gestation with no family history of cystic fibrosis. INTERVENTIONS: Offering counselling and carrier testing for cystic fibrosis, either to women in the first instance (stepwise) or to couples (couple screening). MAIN OUTCOME MEASURES: Uptake rates; anxiety; knowledge of cystic fibrosis and carrier status (both partners); attitudes to health, pregnancy, the baby, and screening (both partners); and uptake of carrier testing by relatives. RESULTS: Uptake of screening was the same for both approaches (90%). After delivery most women remembered test results and their meaning, but 53/253 (21%) of those with negative results of couple testing had forgotten that repeat testing would be advisable if they had a pregnancy with a new partner. With stepwise screening women identified as carriers had high levels of anxiety when results were received (mean anxiety score 52.3). This dissipated with a reassuring partner's result (carriers' mean anxiety score 36.1) to levels similar to those receiving negative results from couple screening. Of those receiving negative results, women who had stepwise screening were significantly less anxious than those who had couple screening (mean score with result 32.1 v 35.4, 95% confidence interval for difference -4.7 to -2.1). CONCLUSIONS: Couple screening allows carriers to avoid transient high levels of anxiety, but is associated with more anxiety and false reassurance among most screenees who will test negative. Stepwise screening gives carriers and their relatives genetic information and is, in our opinion, the better method. PMID- 7866215 TI - Preregistration house officers in general practice. AB - OBJECTIVES: To obtain from house officers who had rotated through general practice in their pre-registration year their views about their experience; and, separately, to compare the overall hours and type of work performed by hospital based and general practice based house officers. DESIGN: Postal questionnaire; and self recording of working hours and duties during four consecutive weeks. SETTING: Inner London teaching hospital and nearby general practice. PARTICIPANTS: 28 preregistration house officers in general practice, 1981-91; and 12 preregistration house officers, four each in medicine, surgery, and general practice. RESULTS: 26 out of 28 questionnaires were returned (response rate 93%). Twelve respondents were following or thinking of following a career in general practice. Twenty five respondents were satisfied with the clinical and educational aspects of the general practice rotation and would recommend the rotation, and 25 thought four months was about the right length of time in general practice. With regard to hours and type of work performed, hospital based house officers worked on average 55.5 hours a week (excluding on call), with an average of 12.5 hours (22.5%) spent in clinical activities; general practice based house officers worked about 41 hours a week, of which 24 hours (58%) were in clinical activities. House officers in hospital received less than one hour's specific teaching a week; those in general practice received nearly three hours' a week. CONCLUSIONS: A preregistration rotation in general practice is a popular alternative to the hospital based rotation. Although this is a limited study, other medical schools should consider introducing general practice options for preregistration house officers. PMID- 7866216 TI - Withholding consent to lifesaving treatment: three cases. AB - The refusal of children or their parents to consent to treatment that professionals regard as essential always results in a dilemma. Responding to such refusals demands careful and sensitive clinical and thicolegal intervention and close cooperation among professionals, in particular doctors and social workers. Since the introduction of the Children Act 1989 the number of cases in which children have withheld consent to lifesaving treatment has risen, and it is now increasingly recognised that children have a right to have their views legally represented if a local authority or health authority seeks a court's leave to carry out treatment. Professionals have to consider which legal route, under either the Children Act or the Mental Health Act, is likely to be best for the individual child. PMID- 7866218 TI - Management for doctors. Management accounting. PMID- 7866217 TI - Clinical pharmacology and therapeutics. PMID- 7866219 TI - ABC of rheumatology. Fibromyalgia syndrome. PMID- 7866220 TI - The World Health Organisation. WHO in Europe: does it have a role? AB - WHO is under pressure from all sides to justify its existence. Donors want to know what they are getting for their money, and health professionals question the relevance of the organisation's work. The pressure to justify itself is perhaps strongest of all in Europe, where most member countries have fully fledged health infrastructures and high overall levels of health. Now there is the additional threat of encroachment into the field of public health by the European Union. The disintegration of the Soviet bloc has given WHO's regional office in Europe a new sense of purpose and led to a major shift in resources towards the countries of central and eastern Europe. But WHO's critics are calling for a different shift in the way its European office works: from its current concentration on broad based policy issues to the nitty-gritty of health care management and delivery. PMID- 7866221 TI - Smoking and death. Public health measures were taken more than 40 years ago. PMID- 7866222 TI - Environmental lead and children's intelligence. Cleveland study hypothesis was not confirmed. PMID- 7866223 TI - Environmental lead and children's intelligence. Obvious hypothesis is ignored. PMID- 7866224 TI - Environmental lead and children's intelligence. Taiwan results are not included. PMID- 7866225 TI - Living close to industry. PMID- 7866226 TI - Monitoring effects of deprivation on health. PMID- 7866227 TI - Teenage pregnancy and deprivation. PMID- 7866228 TI - Inequalities in health. ...or are they? PMID- 7866229 TI - Inequalities in health. Are increasing... PMID- 7866230 TI - Payment for blood donations in Germany. PMID- 7866231 TI - Immunising infants at risk of hepatitis B. Community programme boasts initial success. PMID- 7866232 TI - Immunising infants at risk of hepatitis B. Parent held vaccination card may improve uptake. PMID- 7866233 TI - Length of hip axis and rate of hip fracture. PMID- 7866234 TI - Prophylaxis against malaria. PMID- 7866235 TI - Transmission of tuberculosis in patients with HIV infection. PMID- 7866236 TI - Travel prophylaxis. Figures in study were incorrect. PMID- 7866237 TI - Travel prophylaxis. Assumptions were confusing. PMID- 7866238 TI - Travel prophylaxis. Journals should develop guidelines for economic evaluations. PMID- 7866239 TI - Pigments in breast fluid. What are they? PMID- 7866240 TI - Diabetes in the developing world. PMID- 7866241 TI - Pharmaceutical donations to eastern Europe. PMID- 7866242 TI - [Somatic gene therapy--aspects from theological discussion]. PMID- 7866243 TI - Caffeine, health and commercial interests. PMID- 7866244 TI - Potential development of community oriented HIV outreach among drug injectors in the UK. AB - Given the current epidemiological and behavioural risk profile of HIV infection among injecting drug users in the UK, the main strategic task continues to be to develop interventions to prevent the spread of HIV infection. Outreach to drug injectors is an important part of the wider UK HIV prevention strategy. This paper reviews critically and reassesses practically the role of outreach interventions among drug injectors in the UK. It is argued that despite the development of innovative outreach activity, the full potential of outreach has not been realized due to its theoretical orientation and in-built structural limitations. Outreach has predominantly operated with an 'individual' orientation, aiming to work with individual clients to help them to change their behaviour, gain access to services, or to become better users of services. The main thesis of this paper is that current outreach provision needs to be complemented by 'community change' models which seek to engender changes in the social etiquette of drug use within communities of drug injectors. The paper argues that the social networks through which HIV may be transmitted are the same social networks that may be coopted for HIV prevention. Future outreach services must turn to these networks as a way of targeting and encouraging changes among broad populations of drug injectors. Such models might use indigenous advocates, working within social networks, supported by community outreach facilitators. PMID- 7866245 TI - Trends in alcoholism among male doctors in Scotland. AB - Alcohol abuse within the medical profession has long been an issue of concern. Recently, the General Medical Council reported that half of the doctors reported for health difficulties liable to affect professional competence were found to have an alcohol problem. This paper examines how rates of alcoholism among male doctors in Scotland have changed over the last three decades. Admission and discharge rates for doctors to psychiatric inpatient beds with diagnoses of alcoholism are compared with non-medical professions, for the years 1963-87. The results, assessed in the light of changing Standardized Mortality Rates for liver cirrhosis for the medical profession, suggest that doctors as a group remain at a higher risk of alcoholism compared to other professionals, but that this increased risk appears to be largely accounted for by a cohort of heavy-drinking doctors over the age of 45 years. PMID- 7866246 TI - Is having an alcoholic father hazardous for children's physical health? AB - Five hundred and ninety-nine French-Canadian pre-adolescent children for whom the alcoholic status of the parents was known were subdivided into eight groups, according to family structure (intact, non-intact), alcoholic status of the father (alcoholic, non-alcoholic) and gender of the target child (girl, boy). ANCOVAs were conducted (controlling for income, a factor which contributes to illness) for health-related variables in order to test the hypothesis that children of alcoholic fathers have more physical health problems compared to children without alcoholic fathers. Data pertaining to use of medical services, serious and minor illnesses and pregnancy-related events were analysed. It was found that overall, pre-adolescent children of alcoholics were not more ill than children of non-alcoholics. There were, however, some differences worthy of note. Children of alcoholics had significantly lower birthweights than the children of non-alcoholics. Boys in non-intact alcoholic families were of shorter stature than the other children. A three-way interaction showed that daughters of alcoholics and sons of non-alcoholics living in non-intact families were more likely to have used psychologists' services, as were sons of alcoholics in intact families. The results were discussed in terms of the heterogeneity of alcoholic families as well as the need to identify subgroups of children of alcoholics who are at risk. PMID- 7866247 TI - A comparison of DSM-III-R, DSM-IV and ICD-10 substance use disorders diagnoses in 1922 men and women subjects in the COGA study. Collaborative Study on the Genetics of Alcoholism. AB - A research interview was used to evaluate the relationships between DSM-IV, DSM III-R and ICD-10 diagnostic criteria for substance use disorders. The sample of 1992 subjects, including both men and women, was composed of subjects and their relatives from the Collaborative Study on the Genetics of Alcoholism (COGA) study. With regard to diagnoses of substance dependence, the analyses revealed tha the proportions of individuals diagnosed in the three systems were similar, with the highest numbers observed for DSM-III-R, the lowest for ICD-10 and the figures for DSM-IV between the two. The kappas for dependence diagnoses ranged from 0.54 to 0.83, with the majority at 0.7 and higher, indicating that the same subjects were being given the same labels in the three systems. However, the criteria for abuse or harmful use resulted in rather disparate proportions labeled across the three systems, with kappas that rarely exceeded 0.10. PMID- 7866248 TI - The impact of alcohol beverage container warning labels on alcohol-impaired drivers, drinking drivers and the general population in northern California. AB - Using data collected in a random-digit dial telephone survey in a northern California county, an examination of the impact of alcohol beverage container warning labels was conducted. In a broadly conceived approach to the possible impact of warning labels, we examined recall and content as well as risk assessment and the use of warning labels as public policy to combat drunk driving. In a repeated measures pre- and post-design, respondents reported significantly higher recall of labels and their content in the post-introduction period. Evidence from a multivariate analysis of post-introduction data indicate that both drinking drivers and impaired drivers (based on self-reports) were more likely to recall the labels and their content, an indication that warning labels are reaching "at risk" individuals. In addition, increases in the perceived risk of driving and drinking are consistent with the notion that warning labels, as one part of a larger social movement, are helping to create an atmosphere in which drinking and driving is less acceptable. However, our findings also indicate that, at least among at risk drinking and impaired drivers, increased use of public policies such as warning labels in an effort to reduce the negative consequences of drinking and driving may generate a public opinion backlash. PMID- 7866249 TI - Negative alcohol expectancy predicts post-treatment abstinence survivorship: the whether, when and why of relapse to a first drink. AB - Using survival analysis, the association was explored between positive and negative alcohol expectancies measured on admission to a non-residential alcohol dependence treatment unit and post-treatment relapse to a first drink (first slip). A reliable association between negative alcohol expectancy (but not positive) and relapse was found. The active negative alcohol expectancies were distal rather than proximal: proximal expectancies surround consumption ('same day' expectancies) and distal expectancies relate to the 'next-day' following consumption or those longer term expectancies coming from 'continued drinking'. Only the 'next day' component of distal expectancies formed a reliable association with relapse. The use to which negative alcohol expectancy as measured by the Negative Alcohol Expectancy Questionnaire might be put is discussed in terms of (i) a bottom-up representation of motivation for recovery to help treatment match and (ii) a provisor of detailed, client-specific information for structuring motivational interventions. PMID- 7866250 TI - Suicide among drug addicts in Norway. AB - The impact of drug addiction in suicide with respect to gender and trend changes in drug addiction was assessed from Norwegian data on 1608 drug addicts admitted to treatment over the past three decades. The mean annual mortality rate was 2.3%, and 14.7% of those who died committed suicide. The incidence density of suicide was significantly higher among drug addicts than in the total population, and the excess mortality by suicide was higher for women, higher in the youngest age group, and higher for those who died during the 1970s. No differences in suicide intensity were found between male and female drug addicts, whereas an effect of admission period on suicide intensity was found for women but not for men. Hence, among female drug addicts, those admitted to treatment in the 1970s and 1980s tended to take their own lives during a shorter observation period than those admitted during the 1960s. The degree to which the elevated risk of suicide among drug addicts varies with gender and period is discussed with reference to the impact of gender roles and varying features of drug addicts in Norway over time. PMID- 7866251 TI - Is the association between drug use and delinquency weakening? AB - In this paper we examine period or secular changes in the association between drug use and delinquency among Ontario adolescent students between 1983 and 1991. The results show that during this period drug use and drug-selling declined significantly, whereas reported non-drug-related delinquency increased. In addition to differing secular trends in rates of drug use and delinquent behaviour, the association between the two behaviours weakened. There was a steady decline in the correlations between drug use and delinquency across time, and the typological patterning of drug use and delinquency changed significantly. PMID- 7866252 TI - The use of benzodiazepines among regular amphetamine users. AB - The relationship between benzodiazepine and regular amphetamine use was examined in a sample of 301 regular amphetamine users. Benzodiazepine use was widespread, with 37% of subjects having used them in the month preceding interview, and 55% in the preceding 6 months. Injectors of amphetamines were more likely to have ever used, and to be currently using, benzodiazepines. Comparisons of benzodiazepine users with other subjects indicated that benzodiazepine users had higher levels of polydrug use and psychopathology, as well as poorer health and social functioning than non-users. The odds of benzodiazepine using injectors having injected with a borrowed used needle in the preceding month were 3.8 times of those of non-benzodiazepine-using injectors. These results are consistent with studies of other groups of illicit drug users, such as heroin users, in indicating that benzodiazepine use is associated with greater levels of risk and psycho-social dysfunction. PMID- 7866253 TI - Unemployment and change of tobacco habits: a study of young people from 16 to 21 years of age. AB - In a cohort study of 1080 pupils who were followed for 5 years from when they left compulsory school (from age 16 to age 21 years), smoking habits were found to correlate with unemployment among both boys and girls. Pupils who were smokers in school had a higher risk of becoming unemployed than non-smokers. Irrespective of early smoking, smoking habits developed more unfavourably among unemployed young people than among those with no unemployment during the period studied. The odds ratio of being a smoker at the age of 21 years when unemployed more than 20 weeks during the observation period, compared with those without or with short unemployment, was 2.44 for men and 3.45 for women. When adjusted for the influence of socio-economic background, education, economy and smoking habits at the start of the period, the odds ratio was 1.7 (95% CI 1.01-2.86) for men and 2.0 (1.13-3.53) for women. The adjusted odds ratio for increasing or starting smoking during the period was 1.5 (95% CI 0.89-2.56) for men and 2.0 (1.18-3.35) for women. No significant correlation was found between snuffing and unemployment. Thus, it seems that unemployment is a risk factor for development of tobacco smoking in young people, especially among women. PMID- 7866254 TI - Pseudoaneurysm in injecting drug abusers: cases from India. AB - Pseudoaneurysm, a known complication of arterial needle puncture, is also an uncommon complication of parenteral drug abuse. India is currently witnessing an upsurge of abuse of injectable drugs. Five cases of pseudoaneurysm developing as a complication of intra-arterial drug abuse are reported. The need for early recognition and proper timely intervention is highlighted. PMID- 7866255 TI - Benzodiazepine use among injecting drug users. PMID- 7866256 TI - Would standard drink labelling result in more accurate self-reports of alcohol consumption? PMID- 7866257 TI - The effects of HIV infection on the development of methadone maintenance treatment in Spain. PMID- 7866258 TI - Long-term results of ab externo neodymium:YAG cyclophotocoagulation. AB - Neodymium: YAG cyclophotocoagulation (CPC) was performed in 128 eyes of 123 patients with refractory glaucoma. In each eye, 40 burns delivered with energy of up to 7 J were placed 1.5 mm behind the limbus in a 360 degrees pattern. The minimal follow-up period was 24 months, with the mean being 36.9 (range, 24-84; SD, 5.8) months. The mean intraocular pressure was 35.0 (range 23-54; SD, 12.2) mmHg preoperatively, 20.6 (range 15-24; SD, 3.5) mmHg after 1 year, and 20.2 (range 12-24; SD, 8.1) mmHg after 2 years. A total of 25 eyes (19.5%) lost 2 or more lines in visual acuity. Success was defined as a lowering of intraocular pressure by > 30% and a decrease in visual acuity of < 2 Snellen lines. By this definition the success rate was 52.4%. There was no correlation with either the diagnosis, the stage of the disease, or the pigmentation of the trabecular meshwork, although patients with secondary traumatic or uveitic glaucoma tended to be less responsive to CPC. The most common acute complication of treatment was transient corneal edema. Phthisis bulbi developed in 1 eye (0.8%). In conclusion, CPC achieved satisfactory long-term control of intraocular pressure in the majority of patients with severe late-stage glaucoma. PMID- 7866259 TI - Validity of two-dimensional data obtained with the Heidelberg Retina Tomograph as verified by direct measurements in normal optic nerve heads. AB - The Heidelberg Retina Tomograph (HRT) was recently developed to measure two- and three-dimensional parameters of the optic disc. The instrument gives measurement results on an absolute scale; the validity of the scaling has never been proven in the living eye. Eight phakic eyes (eight patients) scheduled for subsequent pars plana vitrectomy were selected for this study. The optic disc was scanned using the HRT. During vitrectomy, the disc was measured directly using a modified retina spatula that had a 2.5-mm scale with a grading of 1/10 mm at the tip. The measurement was recorded with a high-resolution video system adapted to a Zeiss operation microscope. We used a vitrectomy contact lens with a flat surface. First we looked for reference points along the disc margin that could be clearly identified on both images, then we determined the distances between these points. Calculations from HRT data followed according to the software used in this instrument. Calculations from video images were related to the grading of the intraocular scale instrument. As determined using HRT software version 1.08, the mean ratio of HRT distances obtained by direct video measurements was 1.031 (SD, +/- 0.099; SE, +/- 0.035). No significant correlation between the ratio and the ametropia of the eyes could be verified (r = 0.506, P = 0.20). On average, the two-dimensional measurements of the HRT were correct. Furthermore, we used software version 1.07, which does not correct the image size depending on refraction, and found that the mean ratio of HRT distances obtained direct video measurements was 0.985 (SD, +/- 0.108; SE, +/- 0.038).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866260 TI - Adaptation of the tear film to work in air-conditioned rooms (office-eye syndrome). AB - To detect mechanisms of tear-film adaptation to a dry climate, we investigated co workers in our hospital with air-conditioned rooms. Three groups were formed according to the time of occupancy (6 months to 2 years, 2-4 years, and 4-6 years) and were compared with a control group. The number of patients with frequent dry-eye complaints increased up to 48%, reaching a steady state after 2 4 years. The breakup time was slightly reduced (decrease, 17.5%; P < 0.01) and also reached a steady state after 2-4 years. The tear-ferning test, however, showed a highly significant improvement (P < 0.01). A slight reduction in the Schirmer test was found. Our study indicates that improved tear quality is important for adaptation to long-standing increased evaporation of the tear film. PMID- 7866261 TI - Treatment of endogenous uveitis with anti-CD4 monoclonal antibody: first report. AB - A patient with endogenous uveitis was treated with a chimeric monoclonal anti-CD4 antibody. This patient with long-standing therapy-refractive uveitis did not benefit immediately from antibody infusions, although the frequency of uveitis relapses was sharply reduced after this therapy. After treatment with the monoclonal antibody, this patient's response to conventional immunosuppression improved. The patient had very low CD4+ T-cell counts before the beginning of antibody therapy. In this case, peripheral T-cell counts slowly increased. Antigen-specific T-cell responses to retinal S-antigen in this patient were significantly elevated only just prior to a clinical relapse. The initially high level of spontaneous T-cell proliferation normalized after antibody infusions. PMID- 7866262 TI - Ocular microangiopathic syndrome in patients with acquired immunodeficiency syndrome and its relationship to alterations in cell adhesion and in blood flow. AB - Ocular microangiopathic syndrome is the most frequent ophthalmic finding in patients with acquired immunodeficiency syndrome (AIDS). Ocular microvascular changes, including cotton-wool spots, are closely associated with neuroretinal and cognitive deficits in patients infected with the human immunodeficiency virus type 1 (HIV-1). Cell adhesion has become an important pathogenetic concept in infectious diseases. We studied 39 patients with AIDS by indirect ophthalmoscopy and by slit-lamp biomicroscopy. Cotton-wool spots were counted as an indicator of retinal microvasculopathy. Conjunctival blood-flow sludging in conjunctival vessels was determined by a standardized rating scale as an indicator of blood cell adhesion abnormalities. Parameters of immunosystemic damage were determined by fluorescein-activated cell-sorter scan, radioimmunoassay, and enzyme-linked immunosorbent assay. Conjunctival blood-flow sludging was present in 92% of our patients, and cotton-wool spots were observed in 44%. Cotton-wool spots occurred only in patients with significant blood-flow sludging, and the quantity of cotton wool spots was closely associated with blood-flow sludging (r = 0.64, P < 0.0001). Lower correlations were found between the numbers of cotton-wool spots and the serum level of neopterin (r = 0.40, P = 0.01) or the CD4+ count (r = 0.39, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866263 TI - Intraocular thymoxamine or acetylcholine for the reversal of mydriasis. AB - In a placebo-controlled prospective study, thymoxamine 0.02% or acetylcholine 1.0% or thymoxamine 0.01% plus acetylcholine 0.5% were used intraocularly to reverse mydriasis during cataract surgery. Prior to surgery, pupils were dilated with scopolamine 0.25%, tropicamide 1%, and phenylephrine 10%. At the end of surgery, 228 eyes were randomly assigned to 1 of 4 different treatments: 57 eyes each received intracamerally thymoxamine 0.02%, acetylcholine 1%, a combination of both drugs, or placebo. At 5 min posttreatment, there was a significant mean pupillary constriction of 1.86 +/- 0.67 mm following acetylcholine administration and 1.53 +/- 0.80 mm following thymoxamine application as compared with the placebo group, in which the pupillary diameter remained almost constant. For the combination of acetylcholine plus thymoxamine the effect was fully additive, with a pupillary constriction of 3.42 +/- 0.98 and 4.04 +/- 1.02 mm being observed at 5 and 10 min posttreatment, respectively. No drug-related side effect was detected. We conclude that thymoxamine can be useful during surgery as an intraocular miotic to reverse mydriasis and can considerably enhance miosis when given in combination with acetylcholine. PMID- 7866264 TI - An electrophysiological correlate of learning in motion perception. AB - We investigated learning in a motion-detection task using both psychophysical and neurophysiological methods in normal humans. A total of 20 naive observers had to discriminate between a small motion to the left versus to the right (jump displacement) or between a motion upward versus downward. Their performance improved significantly within less than 30 min in discriminating between directions in the psychophysical jump-displacement task. The improvement of performance with practice was very specific and did not transfer to the same stimulus rotated by 90 degrees. After training for the same task, multichannel evoked-potential recordings changed significantly in component latency and in the distribution of field potentials. This indicates that neuronal ensembles rather than single cells are involved in perceptual learning. Significant differences between the potential distributions occur for potentials at latencies of less than 100 ms over the occipital pole, suggesting an involvement of and plasticity in the primary visual cortex of human adults. PMID- 7866265 TI - Dual rod pathways in complete achromatopsia. AB - The vision in typical complete achromatopsia is mediated only by rods. To provide more information about the physiological basis of this disorder, we investigated in a typical complete achromat the electrophysiological correlate of the psychophysically established 15-Hz-flicker nulling phenomenon. This phenomenon is believed to be the result of destructive interference between two independent rod pathways. We obtained dark-adapted Ganzfeld electroretinogram (ERG) recordings at 15 Hz with increasing stimulus intensities in the scotopic range and compared the results of the typical complete achromat with those of a normal observer. In both observers the 15-Hz ERG signal reached a minimum at retinal illuminances associated with the perceptual null and reversed in phase as the null was traversed. In comparison with the normal observer, however, the null in the achromat was found at higher scotopic retinal illuminances (ca. 0.4 log unit). Furthermore, the loss in amplitude associated with the null was much more evident, the decline in amplitude was steeper, and the phase shift of 180 degrees was accelerated. PMID- 7866266 TI - Atypical presentations of Best's vitelliform macular degeneration: clinical findings in seven cases. AB - The clinical findings obtained in seven patients from four families with atypical vitelliform macular degeneration are described. Five patients had an onset of the disease in childhood and two patients, at the age of 45 years. Their visual acuity was mildly reduced (0.52 +/- 0.27). The fundus showed variable changes with single or multiple central or paracentral yellowish subretinal exudates and deposits, sometimes surrounded by scars. Both eyes were affected in all patients. The scotopic and photopic electroretinograms were normal in all cases. The electrooculogram (EOG) showed a significant reduction of the light rise in all affected eyes, and in five eyes a reduction in the dark trough could be observed. In three clinically unaffected first-order relatives with normal fundus appearance, the light rise of the EOG was reduced, thus identifying them as gene carriers. The clinical features of atypical vitelliform macular degeneration are discussed with respect to similar diseases that must be excluded and may give reason for misdiagnosis. PMID- 7866267 TI - Effect of UV-A light on the catalase activity in the vitreous body of calf eyes. AB - The present paper reports on the effects of UV-A light on the catalase activity of the calf eye vitreous. A total of 26 eyes were irradiated with UV-A light for 3 h and the catalase activity was compared with that of unirradiated eyes. An increase in activity by 33% was shown in the irradiated eyes. The reason for this increase is the induction of radical formation by short-wave light with subsequently intensified catalase formation or release to enable binding of the radicals formed by the cells. The vitreous must therefore be protected from UV-A light. PMID- 7866269 TI - Immunological findings in patients with myelodysplastic syndrome. AB - Activation of monocytes and granulocytes in vitro by cytokines, in vivo administration of cytokines, as well as in vivo cytokine production due to infectious and inflammatory diseases causes changes of the surface expression density of certain membrane molecules. In recent studies we attempted to determine the feasibility of using flow cytometric immunophenotyping as a tool to develop a sensitive parameter for detecting infections at an early stage of disease when clinical parameters are still negative. Since infections are an important factor determining the clinical course of myelodysplastic syndromes (MDS), early detection of infection might be beneficial for these immunocompromised patients. We indeed found activation-associated immunophenotypic changes of cell surface antigens on monocytes and granulocytes of clinically infection free MDS patients suggesting enhanced immune activity in these patients, most likely due to latent or beginning infections. In particular, analyses of the expression density of receptors for IgG (Fc gamma Rs), complement receptors, and certain activation-associated surface molecules such as the CD67 and the M5 molecule seem to be of clinical relevance. We will also discuss findings concerning changes of cytokine levels and functional alterations of immunologic parameters in MDS patients. PMID- 7866268 TI - Identification of risk factors in patients treated for first relapse of Hodgkin's disease. AB - This review focuses on potential risk factors in patients relapsing with Hodgkin's disease after a first chemotherapy/radiation therapy induced complete remission. This patient group usually presents with highly treatment responsive disease and has become one of the target groups for consideration of salvage high dose chemotherapy with stem cell/autologous marrow support (HDC/ABMT). It is currently not clear to which patients in first relapse this treatment should be offered. The knowledge of certain risk factors could be of great help in assessing such patients. A first group of risk factors are those assessable at initial diagnosis: sex, age, histology, Ann Arbor stage, tumour bulk and some laboratory parameters. A second group of risk factors are those present at the time of relapse: time to relapse, extent of disease at relapse, B-symptoms and performance status, extra nodal lesions at relapse or a relapse within an irradiated field. Age below 50 years seems to exert a small influence on outcome but becomes a major problem above that. There is a small number of characteristics such as the time from the end of initial treatment to relapse or B-symptoms at relapse which seem to be the most prominent factors predicting for freedom from second failure (FF2F). Patients who relapse more than one year after finishing primary chemotherapy and who are free of B symptoms at relapse have a quite favourable outcome after salvage treatment. If their disease is not bulky and is confined entirely to a modest number of previously unirradiated lymph node sites, wide field irradiation offers a reasonable chance of disease control. If their recurrence is bulky, extra-nodal or in a previously irradiated site, the patient's prognosis after HDC/ABMT is excellent. Patients who relapse less than one year after primary chemotherapy or with B symptoms at the time of relapse have a less satisfactory outcome after any available salvage treatment. Trials comparing various HDC/ABMT regimens or novel approaches built on standard dose chemotherapy and irradiation are needed to find better treatments for such patients. Such patients with early or symptomatic relapses who cannot be enrolled in prospective comparative trials should be offered HDC/ABMT while we search for better treatments. Larger trials with a prospective analysis of the risk factors are needed for us to be able to decide which treatment will be the optimal choice for our patients. PMID- 7866270 TI - Myeloperoxidase gene expression in normal granulopoiesis and acute leukemias. AB - Myeloperoxidase (MPO) is an abundant heme protein found in granulocytes and monocytes, which plays an important role in host defense against infection. MPO enzyme activity as determined by light microscopic cytochemistry has long been an important marker used in the diagnosis of acute leukemias and other hematopoietic disorders. Recently, MPO expression has been studied at the electron microscopic level, and monoclonal antibodies (mAbs) against MPO protein have been developed. Furthermore, techniques and probes for analysing MPO expression at the RNA level are now available. This has made possible more extensive studies of MPO expression in a wide range of neoplastic and preneoplastic blood disorders. This review will discuss the fundamental biology of MPO as well as recent developments in our understanding of MPO expression in leukemic cells and cell lines of various lineages. PMID- 7866271 TI - HLA homozygosity and shared HLA haplotypes in the development of transfusion associated graft-versus-host disease. AB - We review the pathogenesis, epidemiology and patient cases of transfusion associated graft-versus-host disease (TA-GVHD) in the context of host inability to eliminate viable donor T-lymphocytes. This review is based on the published English-language literature pertaining to TA-GVHD, including case reports with HLA data on transfusion recipients as well as blood donors. The role of shared histocompatibility antigens between the donor and the recipient in promoting TA GVHD is discussed critically. Since TA-GVHD is usually a fatal disease for which effective therapy is lacking, prevention is of utmost importance and guidelines for gamma-irradiation of cellular blood products are presented. TA-GVHD has been described in immunodeficient as well as in immunocompetent hosts, and following blood product transfusions from related as well as from unrelated donors. This review includes analysis of patient data in each of these settings and probability estimates based on principles of population genetics. We emphasize that transfusion of blood products from individuals who are homozygous at the HLA loci to heterozygous recipients who share that HLA haplotype occurs at a frequency proportional to the genetic homogeneity of the population and that the process mediating TA-GVHD in such instances appears to be independent of the host's immune status. PMID- 7866272 TI - Human herpesvirus 6 and pneumonia. AB - Studies of lung tissues and bronchoalveolar lavage specimens from patients with pneumonia have led some investigators to propose that human herpesvirus 6 (HHV-6) can cause pneumonia. As the etiologic role of HHV-6 in pneumonia remains poorly defined, cases of pneumonia that are associated with pulmonary HHV-6 infection are best described as HHV-6-associated pneumonias. The clinical spectrum of HHV-6 associated pneumonia encompasses both mild and severe cases. Most cases reported so far occurred in immunosuppressed individuals following bone marrow transplantation or HIV infection. Some studies have identified coinfections with HHV-6 and other viruses in a surprising number of HHV-6-associated pneumonias. Although no systematic evaluation of treatment regimens is available at this time, coincidental administration of antiviral drugs did not generally result in clinical improvement. Controlled, prospective studies are needed to understand the clinical presentation, clinical course, etiology, diagnosis and treatment of HHV-6-associated pneumonias. PMID- 7866273 TI - Pulmonary fibrosis with megakaryocytoid cell infiltration and chronic myelogenous leukemia. AB - The relationship between fibrosis and megakaryocytic infiltration in the lungs of patients with Philadelphia-chromosome (Ph1)-positive chronic myelogenous leukemia (CML) is the focus of this review. Ph1-positive megakaryocytes are thought to reach and accumulate in the pulmonary vasculature through the marrow-blood barrier. In 21 autopsied patients with accelerated phase or blastic crisis of CML, megakaryocytic infiltration to the lungs was demonstrated in 10 patients, myelofibrosis in 12 patients and both in 5 patients. In 2 of the 10 patients with increased megakaryocytes in the lungs, relatively new fibrosis and alveolar damage in the acute phase were demonstrated with the simultaneous occurrence of myelofibrosis-"myelopulmonary fibrosis."Leakage of mitogenic factors resulting from an abnormality in the packaging mechanism of alpha-granules in these cells termed acquired grey platelet syndrome could cause fibrosis in the lungs as well as the bone marrow. PMID- 7866274 TI - Prognostic factors in autologous stem cell transplantation for multiple myeloma: an EBMT Registry Study. European Group for Bone Marrow Transplantation. AB - Autologous bone marrow- and blood progenitor cell transplantation was performed in 130 patients with multiple myeloma in 16 European centers between 1986 and 1993. At the time of follow-up, 77 patients were alive and 53 were dead. Complete remission after transplantation was obtained in 47% of all patients. The actuarial survival at 65 months was 28%. The median duration of relapse-free survival among patients who were in complete remission after transplantation was 29 months. The following factors were predictive for longer survival and freedom of progression in a univariate analysis: Male sex, age less than 45 years, a low serum-beta-2-microglobulin value at diagnosis, prior administration of only one treatment regimen, response on conventional chemotherapy immediately pretransplant and the use of a preparative regimen including melphalan. The last factor, in addition to stage I disease at diagnosis, male sex and responsive disease immediately pretransplant, were also demonstrated as independent predictive variables for longer survival in a multivariate analysis. Progression free survival was significantly better for patients who were in complete remission after transplantation, as compared to those with persisting signs of disease. We conclude that high-dose chemo-radiotherapy with autologous stem cell transplantation can induce long-term responses, primarily in younger, male patients with chemotherapy-responsive early disease. High-dose melphalan, as single drug or in combination, appeared to be superior to other regimens. The chance of being persistently disease-free seemed to be greatest for patients being in complete remission already before the transplantation. PMID- 7866275 TI - Autologous bone marrow transplantation in multiple myeloma: a single centre experience of 23 patients. AB - We report the complications and outcome of high-dose melphalan and TBI combined with ABMT used in the treatment of multiple myeloma at a single centre. Twenty three patients, aged 65 years or less, who underwent the procedure are reviewed. All had chemosensitive disease. Response to ABMT assessed at 3 months showed 75% of evaluable patients to have further tumour cytoreduction of at least 50%, with 24% of patients who entered ABMT with residual disease eventually achieving CR. There was one toxic death. The overall survival is 60% and the progression-free survival is 49.8% at a median follow-up time of 17 months. Relapse or disease progression has occurred in 27% of patients, of whom half have died. No significant prognostic factors affecting survival were found although those patients with IgG myeloma had a better outcome. Patients transplanted in first plateau appeared to do significantly better if they had been resistant to their first-line chemotherapy but had then responded to further conventional chemotherapy (p = 0.029). PMID- 7866276 TI - The potential of targeted radiotherapy in the treatment of central nervous system leukaemia. AB - We describe the results of clinical studies investigating the role of monoclonal antibody (MoAb) targeted radiotherapy in the treatment of central nervous system (CNS) leukaemia. Seven children, aged 3-16 years, in second or subsequent meningeal relapse of acute lymphoblastic leukaemia (ALL), have been treated. Each patient received a single injection into the cerebrospinal fluid (CSF) of between 629 and 1,702 MBq of 131-Iodine (131I) conjugated to MoAb HD37 (CD19, n = 2), WCMH 15.14 (CD10, n = 4) or both antibodies (n = 1). One patient underwent a course of repeated targeted therapy following his initial treatment. Acute toxicity was manifest in five patients by a transient aseptic meningitis. Myelosuppression was observed in four children. Pharmacokinetic studies investigated whole body, blood and CSF clearance of radioisotope. Progressively more rapid systemic clearance of 131I was noted in the patient receiving repeated therapy, indicating the development of the human anti-mouse Ig (HAMA) response. Dosimetric studies revealed a radiation dose to the red bone marrow of between 0.6 and 2.2 Gy. The dose to the subarachnoid CSF was between 12.2 and 25.3 Gy, over six times higher than that to the surface tissue of the brain and spinal cord and between 40 and 140 times higher than that to the whole brain. In all but one patient, a transient complete response, in terms of disappearance of lymphoblasts from the CSF, was observed. These studies demonstrate the feasibility of targeted radiotherapy in CNS ALL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866277 TI - Long-term follow-up of a CHOP-based regimen with maintenance therapy and central nervous system prophylaxis in lymphoblastic non-Hodgkin's lymphoma. AB - The Eastern Cooperative Oncology Group (ECOG) conducted a phase II trial in adult patients with lymphoblastic non-Hodgkin's lymphoma. Thirty-nine patients with no central nervous system (CNS) involvement were treated with an induction cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)/L-asparaginase regimen and CNS prophylaxis that included intrathecally administered methotrexate given 6 times and 24 Gy midplane cranial radiation in 12 fractions. Thirty-one patients (79%) achieved a complete remission (CR). Of the 31 patients with CRs, 12 relapsed (39%). CNS relapse occurred in three patients. All patients who entered a CR were treated with maintenance CHOP, cytosine arabinoside (AraC), and methotrexate and subsequently with Ara-C and methotrexate. Life-threatening leukopenia or thrombocytopenia was experienced in 69% of patients in the induction phase and in 70% in the maintenance phase. Nineteen of 39 patients (49%) remain in CR with a followup to 9 years. Bone marrow involvement was associated with a significantly worse survival (P = 0.03). PMID- 7866278 TI - Membrane fluidity and adherence to extracellular matrix components are related to blast cell count in acute myeloid leukemia. AB - The level of blast cells in peripheral blood in acute myeloid leukemia (AML) varies in individual patients. The bone marrow egress of hematopoietic cells is an unclear phenomenon in which cell deformability and cytoadhesion to the extracellular matrix are involved. One component of deformability is the membrane fluidity. Using fluorescence polarization, we have studied the fluidity of blast cell membranes from 22 AML patients. This membrane was found to be highly fluid and a statistically significant correlation was found between the increase in membrane fluidity and the number of blast cells in the blood. Studying interaction between blast cells and several components of bone marrow stroma, we found adhesion to fibronectin and fibroblastic extracellular matrix. Adhesion to the extracellular matrix was inversally correlated to the level of blast cells in the blood. The observed increase in membrane fluidity and reduction of adhesion to bone marrow stroma may result in an increase of blast cells egress in AML. PMID- 7866279 TI - Clinicopathological features of adult T-cell leukemia with CD30 antigen expression. AB - Recently, several cases of adult T-cell leukemia (ATL) with CD30 antigen have been reported, but its clinical significance remains unknown. Accordingly, we studied CD30 antigen expression in ATL cases and documented the clinicopathological characteristics of these cases. Immunohistochemical and clinical characteristics were studied in 46 patients with malignant lymphoma or benign lesions of lymphoid tissue, who had antibodies against human T-cell leukemia virus type I (HTLV-I). Monoclonal integration of HTLV-I provirus was demonstrated in the tumor cells in 36 (ATL) of the 46 cases. CD30 antigen expression was evident in seven of these 36 cases (19.4%), however it was not seen in any of the ten cases lacking the integration of HTLV-I provirus. A comparison of ATL cases with and without CD30 antigen expression revealed significantly larger numbers of abnormal lymphocytes in the peripheral blood and lower serum calcium levels in ATL expressing CD30 antigen. PMID- 7866280 TI - Evaluation of carboplatin as a single agent in highly refractory acute myeloid leukemia. AB - Thirteen patients (pts) with highly refractory acute myeloid leukemia (AML) 10 pts with de novo AML and 3 with blast crisis of chronic myeloid leukemia were treated with carboplatin (CP) 150 mg/m2/day through continuous IV infusion for 7 consecutive days. Seven of them received CP at least as third or more line therapy after a median duration of the disease of 26 weeks. None achieved a complete remission but a good hematologic response, with disappearance of circulating blast cells along with correction of bone marrow failure, persisting for 3 months was obtained in one patient and correction of hyperbasophilemia was observed in another with blast crisis of chronic myelogenous. Myelosuppression was the most consistent toxic effect. Two deaths occurred, one from renal acute failure and the other from sepsis. Median survival after CP was 8 weeks (range 4 days-11 months) and the majority of patients were able to return home. When used as a single agent and with the dose-schedule used in this study, CP does not appear effective in refractory AML. Other studies are necessary to assess its role at an higher dose or in combination with other agents in earlier phases of the disease. PMID- 7866281 TI - Cyclosporin A inhibits cytokine-induced proliferation in B-chronic lymphocytic leukemia. AB - We investigated the effects of the immunosuppressant cyclosporin A (CsA) on proliferation of neoplastic B-cells from patients with B-chronic lymphocytic leukemia (B-CLL). Cell growth was induced in vitro by tumor necrosis factor alpha (TNF-alpha (8/16), interleukin 2 (IL-2 (9/16) or both (7/16), in 4 cases spontaneous proliferation was observed. We were able to demonstrate that CsA inhibits cytokine-induced proliferation, as measured by [3H]-thymidine incorporation, in all cases responsive to TNF-alpha or IL-2 as well as in spontaneous proliferation. CsA did not increase the fraction of trypan blue positive cells or apoptosis. Growth inhibition by CsA occurred in a dose dependent manner: 100 ng/ml CsA was the optimal concentration which blocked about 90% of cytokine induced or spontaneous proliferation. We could also demonstrate that the effect of CsA was reversible and that no blocking effect was observed when CsA was added later than 48 hours after stimulation. Cell cycle analysis using propidium iodide as a DNA stain demonstrated that CsA prohibited the progression of B-CLL cells from the G1-phase to the S-phase of the cell cycle. However, we were also able to show that TNF-alpha induced proliferation of hairy cell leukemia (HCL) was not affected by CsA. This observation indicates that the inhibitory activity of CsA seems to be restricted to only a few haematological diseases such as B-CLL. PMID- 7866282 TI - The effect of human myelomonocytic leukemic cell line (M20) derived IL-1 inhibitor on human erythroid cell development. AB - The effect of an inhibitor of IL-1, purified from a human myelomonocytic cell line (M20) on the development of human erythroid cell development was studied. The inhibitor, is a protein of 52 kD molecular weight that is distinct immunologically and functionally from other reported IL-1 inhibitors. The experiments were performed in a two-phase culture system that allows separation of the erythroid cell development into an erythropoietin (EPO)-independent phase, where early erythroid-committed BFUe proliferate and differentiate into the more mature progenitors, CFUe, and EPO-dependent phase, where CFUe further proliferate and mature into hemoglobin-containing orthochromatic normoblasts. The results indicated that in both developmental stages the M20-derived inhibitor reversibly blocked cell proliferation without interfering with cell differentiation. PMID- 7866283 TI - Kinetics of the pleiotropic effect of interleukin 4 on the surface properties of human B-lymphoma cells. AB - Striking antigenic changes were elicited by interleukin 4 (IL-4) in the Farage human B-cell lymphoma line. After 2 days of incubation with IL-4 the expression of CD23, CD54 (ICAM-1), CD58 (LFA-3) was increased while the levels of CD21, CD22, CD38 were diminished. Prolonged incubation of Farage cells with IL-4 for 6 8 days led to increased expression of CD11a (LFA-1) CD39, CD40, and to disappearance of CD21 and CD38. The modulation of antigenic properties of Farage cells was associated with enhancement of their homotypic adhesiveness and the formation of giant clumps of cells. The recovery of Farage cells which had been exposed to IL-4 for six days was not complete and eleven days after withdrawal of the cytokine, these cells still displayed a lower level of CD21 and of CD38 than control cells. Cycling and non-cycling cells did not appear to differ in their antigenic properties, indicating that modification of the antigenic profile did not result from cell selection or cell arrest. These results showed that the pleiotropic effect of IL-4 on various cell surface structures on malignant human B cells proceeds at different rates suggesting that distinct metabolic pathways may regulate their expression. PMID- 7866285 TI - Unique dermatological complication of rhM-CSF treatment. AB - A patient is presented who developed cutaneous papular histiocytic infiltrates after treatment with monocyte colony stimulating factor (rhM-CSF). This is the first reported complication of this type after treatment with this new cytokine. PMID- 7866284 TI - Persistent abnormalities in red cell parameters following treatment of lymphoma. AB - Patients who have recovered from malignant lymphoma are at an increased risk of secondary acute leukemia (AL), and overt AL is frequently preceded by a myelodysplastic syndrome. Although the statistical risk is significant, only a minority of the patients will be so affected. We have reviewed peripheral blood counts of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) treated in the Departments of Hematology at the Edith Wolfson and Chaim Sheba Medical Centers, Israel. Included were only those who went into a complete remission and remained lymphoma free for extended periods. There were 85 patients with HD and 36 with NHL. In both groups peripheral blood counts at diagnosis were within the normal range. A prolonged follow-up (> 4 y), during which no further treatment was given, revealed a sustained increment over time of MCV (delta MCV) both in HD and NHL. A persistent monocytosis in HD patients was also evident. delta MCV was larger in HD. The difference at the end of the follow-up period was as follows: 10.1 fl + 11.8 in HD vs 5.0 fl + 6.2 in NHL, (P < 0.001). In addition, a significant loss of the normal correlation between the MCV and levels of hemoglobin was seen at the last follow-up. The change in MCV was present in all treatment groups, its magnitude increasing from radiotherapy to chemotherapy to combined radio chemotherapy. This trend is in analogy to the risk of secondary AL which is lower in NHL vs HD. Furthermore, it is lowest post radiotherapy and highest when both treatment modalities are used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866286 TI - Two unusual neurological presentations of granulocytic sarcoma in Philadelphia positive chronic myeloid leukaemia. AB - Granulocytic sarcoma (GS) is a rare extramedullary tumour consisting of immature myeloid precursors. It occurs most commonly in association with myeloid leukaemias and myeloproliferative disorders. Rarely there may be no evidence of haematological malignancy. We describe neurological presentations of GS in two patients with Philadelphia (Ph) positive chronic myeloid leukaemia (CML). In both cases the bone marrow was in chronic phase at the time of presentation of the GS, but there was rapid subsequent transformation into the blastic phase. PMID- 7866287 TI - Gastric stump lymphoma. AB - Lymphoma occurring in the post-operative stomach would appear to be very rare with only five previously recorded cases. In three of these, focal lymphoid hyperplasia or pseudolymphoma had been found at the time of the original ulcer surgery, or at subsequent biopsies of the gastric stump or anastomotic sites. These latter three cases developed lymphoma within 11 years of the ulcer surgery as against the 20 years or longer generally found in cases of gastric stump carcinoma. Two cases presenting with gastric stump lymphoma approximately 20 years after Billroth 2 partial gastrectomy are reported. In neither of these two cases, nor in the other two patients previously recorded with post-operative gastric lymphoma 20 or more years following gastric surgery, was luminal focal lymphoid hyperplasia reported at the time of the original gastric surgery. It is postulated that these two small groups may have developed lymphoma due to differing malignant stimuli. PMID- 7866288 TI - Short communication: prolonged severe neutropenia after chlorambucil therapy and prompt reversal with GM-CSF. PMID- 7866289 TI - Purification and biological properties of a cell growth-stimulating factor from Clostridium perfringens FERM P-14028. AB - The active component that stimulates fibroblast growth was purified from cultured Clostridium perfringens FERM P-14028, and a quantitative assay method for the biological activity was established. The active component was named cell growth stimulating factor (CGSF), and the molecular weight of this factor was estimated to be 420 kDa on gel permeation chromatography. CGSF(50-100 ng/ml) stimulated the growth rate of BHK-21 (C-13) cells in the logarithmic growth phase, and shortened the doubling time by 16-18%, but had no effect on confluent cells. These actions were indicated only with medium containing fetal bovine serum. These results suggest that CGSF is a novel protein that regulates cell growth via a mechanism of action different from that of other growth factors. PMID- 7866290 TI - Dual effects of forskolin on glucose utilization in cultured fibroblasts, as observed with the use of glucose analogs. AB - It is well known that forskolin suppresses glucose transport in cell membranes. In the present study, however, we indicated a different effect of forskolin on the uptake of radioactive 2-deoxy-D-glucose (2-DG) by cultured fibroblasts between the values measured in the presence of unlabeled 2-DG and those measured in the presence of unlabeled glucose. In the former case, the uptake was inhibited by forskolin. On the contrary, [3H] 2-DG uptake in the presence of unlabeled glucose was increased by forskolin. These results suggest that the metabolic difference between the two sugars is involved in the above-mentioned difference in the effect of forskolin. This paper presents that forskolin has stimulatory effect on glycolysis in addition to an inhibitory effect on glucose transporter. The findings seem to be of another interest to indicate the relationship between membrane transport and subsequent intracellular metabolism of glucose. PMID- 7866291 TI - Pregnenolone metabolism in testicular homogenates of macaques (Macaca fascicularis): some effects of relaxin and freezing. AB - The metabolism of varying quantities of pregnenolone has been studied in nuclei free homogenates from Macaca fascicularis testes by using capillary gas chromatography, after derivatization of metabolites as O-methyl oximes/trimethylsilyl ethers. Evidence was obtained indicating that both pathways for testosterone biosynthesis were operating. 5-Androstene-3 beta, 17 beta-diol was formed in especially high quantities. Two 16-androstenes, namely 5,16 androstadien-3 beta-ol and 5 alpha-androst-16-en-3 beta-ol, were also quantitatively important as metabolites. Co-incubation of stored homogenates with relaxin resulted in 80-100% reduction of the formation of all metabolites quantified except for 5 alpha-androst-16-en-3-one, which was stimulated. Freezing the homogenates at -10 degrees C for 3 weeks resulted in marked 4- to 6-fold reduction in the yields of testosterone and of the 5-ene and 4-ene metabolites from pregnenolone. PMID- 7866292 TI - The effect of dietary lipid manipulation on hepatic mitochondrial phospholipid fatty acid composition and carnitine palmitoyltransferase I activity. AB - The maximal activity of the overt from of carnitine palmitoyltransferase I (CPT I; EC 2.3.1.21) and its sensitivity to inhibition by malonyl CoA were measured in mitochondria prepared from the livers of rats which had been fed for 10 weeks on either a low fat diet (LF; 2.4% fat by weight) or on one of four high fat diets which contained 20% by weight of either hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO) or menhaden (fish) oil (MO). CPT I activity (i.e. activity per g of liver tissue), was elevated in animals fed the OO, SO or MO diets compared with those fed the LF or HCO diets. Feeding the HCO diet did not result in elevation of CPT I activity compared with feeding the LF diet. CPT I specific activity (i.e. activity per mg mitochondrial protein) was elevated in animals fed SO diet, but not in animals fed any of the other high fat diets. These observations suggest that an elevated fat load is not solely responsible for increasing CPT I activity, but that the fatty acid composition of the diet also plays a role. Hepatic CPT I activity of rats fed the LF diet was most sensitive to inhibition by malonyl CoA ([I50] = 0.53 microM). Each of the high fat diets decreased the sensitivity of CPT I to inhibition by malonyl CoA; CPT I activity in the livers from animals fed the MO diet was the least sensitive to malonyl CoA inhibition ([I50] = 1.8 microM). The fatty acid compositions of the major mitochondrial membrane phospholipids, phosphatidylcholine, phosphatidylethanolamine and cardiolipin were modified according to the fatty acid composition of the diet. Each of these phospholipids had a distinct fatty acid composition and similar effects of dietary lipid manipulation on the fatty acid compositions were observed. Feeding the SO diet resulted in fatty acid compositions which were most similar to those found after feeding the LF diet. Feeding the HCO and OO diets increased the proportions of stearic and oleic acids, respectively, while decreasing the proportion of linoeic acid. Feeding the MO diet resulted in increased proportions of palmitic, palmitoleic, eicosapentaenoic and docosahexaenoic acids and decreased proportions of linoleic and arachidonic acids in each of the phospholipids. It is proposed that the effects of dietary lipid manipulation upon CTP I activity and sensitivity to inhibition by malonyl CoA are due to alterations in the fatty acid composition of the phospholipids in the mitochondrial membrane where CPT I resides. PMID- 7866293 TI - Protective effects of riboflavin and its derivatives against ischemic reperfused damage of rat heart. AB - The effects of riboflavin and its derivatives such as FAD, FMN and lumichrome on the levels of high energy phosphate compounds (ATP and creatine phosphate) and intracellular pH in ischemic reperfused rat hearts were investigated using a Langendorff perfusion technique. 31P-NMR study showed a decrease in the levels of high energy phosphate compounds and pH values in myocardium after 30 min global ischemia and a slight recovery of these levels after a 30 min reperfusion following ischemia. However, in all the hearts perfused with riboflavin and its derivatives during ischemia-reperfusion, a marked recovery of high energy phosphate compounds and pH values were observed. In addition, the cardiac mitochondrial respiratory function was protected from ischemia-reperfusion injury. These results suggest that riboflavin, FAD, FMN, and lumichrome have a protective effect against ischemia-reperfusion injury to rat myocardium in vitro. It is assumed that these substances exert their effect directly in the extracellular space. PMID- 7866294 TI - Phospholipids metabolism in platelets stimulated with collagen. AB - Collagen addition to platelets suspended in Calcium-free medium induces slow shape change followed by fast aggregates formation. Time courses of membrane phospholipids metabolism and arachidonic acid oxidative metabolism indicate that phospholipase C is the immediate target of the stimulus, and subsequently phospholipase A-2 is activated by synergistic action of released calcium and protein kinase C. PMID- 7866295 TI - Photometric estimation of cadaverine oxidation by copper amine oxidase. AB - A simple method for the photometric estimation of 1-piperideine, produced by the action of copper amino oxidases on cadaverine, is described. A discussion on the formation of 1-piperideine from lysine in acidic medium is also reported, together with some observations on the nature of acid 1-piperideine-ninhydrin condensation product. PMID- 7866296 TI - Effect of polyols and sugars on heat-induced flavin dissociation in glucose oxidase. AB - A thermodynamic investigation was carried out on heat-induced flavin dissociation in Aspergillus niger glucose oxidase. Experimental measurements performed by difference spectroscopy showed that the dissociation of the FAD cofactors is a highly cooperative process and is probably related to the extended conformational changes resulting from protein unfolding. Microenvironmental modifications attained by the addition of polyhydric compounds (glycerol, fructose, sucrose and sorbitol) from 10 to 30% by weight were found to hinder the dissociation. The stabilizing effect provided by these substances was interpreted as a consequence of preferential exclusion phenomena, which are likely to be determined by the perturbation of the surface tension of water, in the case of sugars, or by the solvophobic effect, in the case of glycerol. PMID- 7866297 TI - A lysosomal arylamidase is a member of a larger family of peptidases in lysosomes. AB - One form (form VI) of lysosomal arylamidase, having a molecular weight of 135,000 and an isoelectric point of 7.8, was purified from rat liver to apparent electrophoretic homogeneity. The enzyme consisted of three identical polypeptides with a molecular weight of 45,000, as judged by disk electrophoresis in the presence of sodium dodecyl sulfate (SDS). The enzyme hydrolyzed di- and tripeptides. The enzyme released a N-terminal amino acid from Leu5-enkephalin and Met-Lys-bradykinin; these have a tyrosine and a methionine at the N-terminus, respectively. The enzyme did not hydrolyze bradykinin, angiotensin and melanocyte stimulating hormone release-inhibitory factor (MIF); these have a basic amino acid, an acidic amino acid, and a proline at the N-terminus, respectively. PMID- 7866298 TI - Thioltransferase can utilize cysteamine as same as glutathione as a reductant during the restoration of cystamine-treated glucose 6-phosphate dehydrogenase activity. AB - Glucose 6-phosphate dehydrogenase (G6PD) [EC 1.1.1.49] is inactivated by the incubation with cystamine very efficiently, but not by oxidized glutathione. This inactivation advanced following the incubation-time and concentration of cystamine. The inactivated-G6PD is restored its activity by the treatment of thioltransferase with 1 mM cysteamine or reduced glutathione (GSH) much more effectively than only by thiols. For the first time, we suggested thioltransferase can utilize cysteamine in stead of GSH during its thiol/disulfide exchange reaction activity. PMID- 7866299 TI - Relationships between protein carbonyls, retinol and tocopherols level in human plasma. AB - Free radical oxidation has been claimed as one of the most important mechanism of damage in aging and in several diseases. Carbonyl content in tissue and circulating proteins is a stable marker of this attack. In 29 apparently healthy subjects (25-89 years old) carbonyl content of plasma proteins and retinol and tocopherols (alpha- and gamma-) were studied. Carbonyls level did not show an increase with age. A good correlation between carbonyls content and gamma tocopherol (r = 0.44, P < 0.05) and a trend with retinol (r = 0.34, P = 0.07) was found, but not with alpha-tocopherol. An inverse correlation was observed between carbonyls and plasma proteins (r = -0.63, P < 0.01) and the natural antioxidant studied showed an increase with age and a good relationship with lipids. These data suggest that retinol and tocopherols, well known scavengers of free radicals, are involved, at least partially, in the prevention of oxidative damage of circulating proteins. PMID- 7866300 TI - Neurospora crassa blue light-inducible gene bli-3. AB - Blue light induces various physiological, morphological and biochemical reactions in the filamentous fungus Neurospora crassa. This light response is accompanied by a global change in gene expression, and several light-inducible transcripts (bli-genes) have been cloned. We isolated the genomic clone of the gene bli-3, whose mRNA we have previously shown to be induced 2 minutes after the beginning of illumination. Its DNA sequence predicted a transcriptional unit of 1050 bp encoding a novel, hydrophilic protein of 209 aminoacids. Comparison to other N. crassa genes revealed a group of inducible genes which share this promoter structure: a well conserved TATA-box, similar transcription start box (TCATCANC) and repeats of pyrimidines (CT) between these boxes. Based upon this group, we propose a consensus sequence for one possible type of inducible promoter in N. crassa. PMID- 7866301 TI - Regulation of mitochondrial cAMP-dependent protein kinase activity in yeast. AB - We have shown that transcription of the yeast (S. cerevisiae) mitochondrial (mt) genome is cAMP-sensitive, via a mt cAMP-dependent protein kinase (cAPK). In relation to that work, we examined whether the BCY 1 gene product functions as regulatory subunit for mt cAPK, as it does for the cytoplasmic enzyme. We demonstrate that mt protein extracts from a bcy 1 strain show no cAPK activity, whereas similar extracts from an otherwise isochromosomal BCY 1 strain show high levels of such activity. Partial purification of mt cAPK from each strain confirms this difference. Photoaffinity labeling with 8-N3[32P]cAMP and highly purified mt protein extracts from the BCY 1 strain identifies one cAMP-binding protein (M(r) approximately 47000), while similar mt extracts from the bcy 1 strain lack all cAMP-binding proteins. These data suggest that BCY 1 regulates yeast mt cAPK, and that inactivation of BCY 1 removes that mt activity from cAMP control. PMID- 7866302 TI - Stabilization and competitive inhibition of beta-carotene 15,15'-dioxygenase by carotenoids. AB - Carotenoids stabilize beta-carotene 15,15'-dioxygenase (CDO) during the isolation of the enzyme from the rabbit small intestinal mucosa using a thiol protector and protease inhibitors and in the course of the enzyme purification. The inhibition of CDO by lycopene, lutein and astaxanthin is competitive. Carotenoids partly protect CDO from the action of both iodacetate and trypsin due to enzyme pseudosubstrate interaction. PMID- 7866303 TI - Enhancement in gastric mucosal laminin receptor expression with ulcer healing by sucralfate. AB - The expression of gastric mucosal laminin receptor during chronic ulcer healing in the presence of sucralfate treatment was investigated. Rats with induced gastric ulcers were treated twice daily for 20 consecutive days either with sucralfate at 100mg/kg or vehicle, and at different stages of treatment used for gastric mucosal laminin receptor quantitation. The assays revealed that accelerated ulcer healing (8 days) in the presence of sucralfate was accompanied by a significant enhancement in the laminin receptor expression. A 2.8-fold increase in the receptor expression over that of controls occurred by the 3rd day of sucralfate treatment, reached a maximum of 3.1-fold increase by the 7th day and remained elevated even after 20 days of treatment. The results attest to the ability of sucralfate to stimulate and promote the events associated with gastric mucosal integrity restoration. PMID- 7866304 TI - Etoposide-resistance in the multidrug-resistant LZ-8 cells. AB - The multidrug-resistant LZ-8 cells were found to exhibit marked resistance to etoposide compared to wild-type, parental V79 cells. The multidrug resistant phenotype did not significantly contribute to this etoposide-resistance. Following exposure of LZ-8 cells and V79 cells to equivalent concentrations of etoposide, there was a dramatic reduction in the number of etoposide-induced stabilized DNA-topoisomerase II complexes in the LZ-8 cells compared to V79 cells, however, this reduction was not found when nuclei isolated from LZ-8 and V79 cells were exposed to equivalent concentrations of etoposide. These results suggest that cytoplasmic factors are involved in the etoposide-resistance of LZ-8 cells. PMID- 7866305 TI - Effect of alloxan-induced diabetes on Na+, K(+)-ATPase activity from discrete areas of the rat brain. AB - The effect of alloxan-induced diabetes was studied on the activity of Na+, K(+) ATPase enzyme which is involved in numerous reactions in the metabolism of the synaptic region, Na+, K(+)-ATPase activity was examined in brain areas such as septum, amygdala, thalamus, hippocampus, pons and medulla, and in hypothalamic areas such as medial preoptic and median eminence-arcuate region. In all these areas studied, diabetes caused a decrease in the activity of Na+, K(+)-ATPase, whereas, insulin administration reversed this effect. The present results may indicate the possible involvement of Na+, K(+)-ATPase in neuropathophysiology of diabetes. PMID- 7866306 TI - Properties of yeast cells depleted of the OSCP subunit of mitochondrial ATP synthase by regulated expression of the ATP5 gene. AB - OSCP is a subunit of the FA stalk sector of yeast mitochondrial ATP synthase complex. Cells of a null mutant for OSCP, constructed by disruption of the chromosomal ATP5 gene of Saccharomyces cerevisiae, exhibited a high level of genetic instability (petite formation). Study of the effects of ablation of OSCP required the development of a progressive depletion strategy. Introduction of a vector bearing an ATP5 gene cassette under GAL1 transcriptional control into null mutant cells gave rise to a stable yeast strain from which OSCP could be depleted in a controlled manner by manipulation of the level of galactose in the growth medium. Cells progressively depleted of OSCP exhibited properties of cellular respiration indicative of a decline in the functional coupling of the catalytic F1 sector to the proton channel F0 sector (normally linked by FA). Cells depleted of OSCP also exhibited a physical uncoupling of F1 from other subunits of the complex such that other FA subunits and F0 subunit 6 were not recovered in immunoprecipitates of ATP synthase complexes. Thus, OSCP plays a role in the assembly as well as function of the enzyme complex. PMID- 7866307 TI - Oxidative DNA damage induced by Cu(II)-oligopeptide complexes and hydrogen peroxide. AB - At physiological pH values, Cu(II)-tetraglycine and Cu(II) complexes with peptides containing a histidyl residue at the N-terminal caused DNA strand breakage in the presence of H2O2, whereas Cu(II) complexes with peptides containing histidyl residue in the second or third position did not. Because of the correlation between the generation of hydroxyl radical and DNA strand scission, a mechanism for the reaction is proposed. PMID- 7866308 TI - Tentative evidence of a rosmarinic acid peroxidase in cell cultures from lavandin (Lavandula x intermedia) flowers. AB - The oxidative stability of rosmarinic acid (alpha-O-caffeoyl-3,4 dihydroxyphenyllactic acid) in lavandin (Lavandula x intermedia) cell cultures was studied in an attempt to explain the decrease in the rosmarinic acid content of aging cell cultures, a process which is associated with the appearance of brown pigments. The oxidation of rosmarinic acid by a partially purified protein fraction was followed spectrophotometrically and by HPLC. The results showed that rosmarinic acid oxidation was almost totally dependent on the presence of H2O2 and protein, and that brownish products were the results of this oxidation, resembling those shown by aging cell cultures. Since this protein fraction contains peroxidase activities and shows the total absence of tropolone-sensitive polyphenoloxidase (catecholase) and laccase activities, rosmarinic acid oxidation is tentatively proposed to be caused by a peroxidase-like activity. These results support the existence of a rosmarinic acid peroxidase in cell cultures of lavandin flowers, which may be involved in the oxidative destruction of rosmarinic acid, and which may also be responsible for the formation of brown pigments during aging, lowering the yields of rosmarinic acid. PMID- 7866309 TI - Increase in <--H+/e- ratio of the cytochrome c oxidase reaction in mitochondria irradiated with helium-neon laser. AB - In order to gain a degree of insight into the mitochondrial component/s responsible of the mitochondria-red light interaction, isolated rat liver mitochondria were irradiated with a Helium-Neon laser (energy dose 2 Joules/cm2, light power 10 mW) and measurements made of the activity of cytochrome c oxidase. A low, but statistically significant increase in the oxygen uptake was found, as polarographically measured, in the presence of rotenone and antimycin A, with ascorbate and TMPD used as substrate pair. Measurements were also made both of the electron transfer and of proton pumping activity: as a result of a major stimulation in the proton pumping activity, about 55% increase of <--H+/e- ratio was found in irradiated mitochondria. PMID- 7866310 TI - Transcriptional regulation of human transglutaminase1 gene by signaling systems of protein kinase C, RAR/RXR and Jun/Fos in keratinocytes. AB - Transglutaminase1 (TGase1) gene is expressed at the late stage of terminal differentiation of epidermal keratinocytes. 12-O-tetradecanoylphorbol-13-acetate (TPA) markedly induced the luciferase activity in cultured rat keratinocytes. FRSK cells, transfected with a luciferase reporter plasmid containing the 0.82-kb 5'-flanking region of the human TGase1 gene, but hardly in non-keratinocytic cells. The TPA-induced luciferase activity was suppressed by retinoic acid, 9-cis retinoic acid, and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). Co transfection with expression plasmids for c-jun and/or c-fos showed that Jun itself induced the luciferase activity, whereas Fos inhibited both the basal and TPA-induced luciferase activity. These results suggested that the signaling systems including protein kinase C, retinoic acid/retinoid-X receptors, and Jun/Fos regulate the transcription of the TGase1 gene. PMID- 7866311 TI - Detection of immunoglobulin binding factor by enzyme-linked immunosorbent assay using two monoclonal antibodies. AB - Immunoglobulin binding factor (IgBF) found in human seminal plasma may be involved in suppressing antibody production against sperm in the female and male genital tracts. In the present study an enzyme-linked immunosorbent assay (ELISA) for IgBF was developed using monoclonal anti-IgBF antibodies. The sensitivity of the method was 20 pg/ml. The method was used to quantify IgBF in sera from women. In addition high levels of IgBF was found in cervical mucus of the uterus and in bronchial washings. The present results suggest that IgBF is found in tissues that are exposed to the external environment and may be a component of the local immunity system. PMID- 7866312 TI - Inductive effect of ginsenoside-Rg1 on tyrosine aminotransferase gene expression in rat primary hepatocyte cultures. AB - Ginsenoside-Rg1 (G-Rg1) present in the roots of Panax ginseng (C. A. Meyer) has been shown to induce the enzyme activity of tyrosine aminotransferase (TAT) EC(2.6.1.5) in rat hepatocyte cultures. Thus, we investigated whether the inductive effect of G-Rg1 may act through glucocorticoid receptor- or cAMP mediated action mechanism in the hepatocyte cultures. G-Rg1 induced the TAT activity by 2-fold with a similar time course to that of dexamethasone in the cell cultures. This effect of G-Rg1 was abolished to the basal level when RU486, a specific glucocorticoid antagonist was added to 10(-5)M. Furthermore, the additive effect of G-Rg1 and dexamethasone was inhibited as well by RU486. G-Rg1 and dibutyryl-cAMP (Bt2-cAMP) also revealed an additive effect but this additive effect was inhibited only to the G-Rg1-induced level by Rp-cAMPS, a specific inhibitor of protein kinase A. From these results, we suggest that the action mechanism of G-Rg1 leading to the induction of TAT activity may be mediated through glucocorticoid receptor binding and may not directly act through cAMP mediated induction mechanism. PMID- 7866313 TI - Is there a need for channelling in the functioning of the protein synthesis initiation factors eIF-2 and eIF-2B? AB - The possibility that channelling is necessary in the initiation of eukaryotic protein synthesis is evaluated. Calculations suggest that despite the very high association rate constant found for the interaction of eIF-2 and eIF-2B under in vitro conditions, it is unlikely that rates in vivo can be high enough to permit measured rates of protein synthesis. Channelling therefore seems a priori a requirement. PMID- 7866314 TI - [Selected topics of immunology in tuberculosis]. PMID- 7866315 TI - [Familial aggregation of lung cancer in families of patients with lung cancer]. AB - For determination of whether lung cancer clusters in families, an analysis was conducted on morbidity-mortality data, occupational and tobacco use practices for family members of 189 lung cancer probands and 211 controls (patients without cancer admitted to hospital because of accidents). Significant increase (1.48) was observed in cancers of all anatomic sites among relatives of lung cancer patients. Overall male relatives of lung cancer patients had 9.5 and female 11.8 greater risk for lung cancer than relatives of controls. This results remained significant after adjusting for age and smoking. PMID- 7866316 TI - [Five year survival of patients treated surgically for cancer metastatic to the lungs]. PMID- 7866317 TI - [The role of pleural needle biopsy and determination of Carcinoembryonic antigen in pleural fluid for diagnosing the etiology of pleural effusion]. AB - Results of histopathological and bacteriological examinations of specimens taken in 213 patients with pleurisy by Abrams' needle biopsy of parietal pleura were presented. Malignant cells were found in histological survey of excisions from pleura in 48/128 patients with final diagnosis of cancer (37.5%). The same examination accompanied by bacteriological survey led to establish proper diagnosis in 41/60 patients with pulmonary tuberculosis (68.3%). In 31 patients with cancer pleural fluid was searched for concentration of the carcinoembryonic antigen (CEA). In this group, in 7/19 patients with negative histological results of pleural biopsy CEA concentrations were markedly increased. This finding strongly supported further searching for malignancy in those cases. Finally, the diagnosis was established due to the pleural needle biopsy in 89/213 patients (41.8%). PMID- 7866318 TI - [Neoplastic metastasis in lungs simulating primary tumor of the respiratory system]. AB - 16 patients with clinical and radiological symptoms suggesting lung disease were described. Metastatic character of process was documented in 7 of them during life and in 9 after death. The pulmonary symptoms without any signs of primary tumor lasted from few months to 3 years. Two patients revealed primary tumor in ovary, 1-in uterus, 4-in thyroid gland, 2-in prostata, 2-in breast, 2-in pancreas, 1-in bone, one in testicle, and 2-in kidney. PMID- 7866319 TI - [Treatment of chronic empyemas in the pleural cavity]. AB - The authors present the results of surgical treatment of chronic empyemas of the pleural cavity in 294 patients treated at the Surgical Department in the years 1980-1992. The methods of treatment are discussed taking in consideration the etiology of the empyemas, clinical presentation, coexistent diseases. In 86 patients (29.3%) decortication with partial resection of the lung was carried out (most often a lobe), in 123 patients (41.8%) a decortication was performed, in 8 (2.7%) thoracoplasty, in the remaining 41 (13.9%) drainage of the pleural cavity was carried out. Out of the 245 subjects treated surgically 3 (1.2%) died; in the remaining patients a full recovery was noted. A full recovery was noted in 22 (53.7%) out of the 41 treated with pleural cavity drainage. Eight patients with esophageal-pleural fistulas in the course of a advanced esophageal cancer died due to advanced malignancy. 11 were discharged with chronic drainage. The latter could not be treated surgically due to a existence of high risk factors. PMID- 7866320 TI - [Efficacy of surgical treatment of non-small cell lung cancer in Poland]. PMID- 7866321 TI - [Surgical treatment of mediastinal tumors from personal material]. AB - 90 patients with mediastinal tumors treated surgically was analysed. It was find, that tumor mostly was localized in anterior superior mediastinum, had benign character and in over half of cases was derived from thymus. 75% of mediastinal tumors were primary. In over 50% patients longitudinal sternotomy was performed. Radical excision of the tumor was possible nearly in 90% cases. PMID- 7866322 TI - [Effect of acute exercise on cardiac arrhythmias in the course of chronic obstructive pulmonary disease]. AB - It is suggested that ventricular arrhythmias may be the reason of sudden death in stable patients with COPD. Strenuous effort might provoke danger ventricular arrhythmias in those patients. The impact of maximal exercise test on cardiac ventricular arrhythmias was studied in 24 patients with advanced chronic obstructive pulmonary disease (COPD). The treadmill, self limited exercise test according to Bruce protocol and accompanied by pulse oximetry was performed during 24 hour Holter monitoring. We found ventricular extrasystoles in all patients, in an average 492 +/- 770, complex ventricular extrasystoles in 17 patients and nonsustained ventricular tachycardia in 8 patients. 81% of all ventricular extrasystoles, 80% complex ventricular extrasystoles and 70% nonsustained ventricular tachycardia occurred during the test and up to 2 hour after the test. Patients with complex ventricular arrhythmias were younger and mostly achieved more MET during exercise, but they did not differ in advancing of COPD as measured by spirometry, gas measurements and echocardiography. Although maximal exercise test enhances ventricular arrhythmias it produced no sustained, symptomatic ventricular arrhythmias in patients with advanced and stable COPD. PMID- 7866323 TI - [Diagnostic problems with a case of primary tuberculosis]. PMID- 7866324 TI - [Primary bilateral lung cancer treated with simultaneous double-sided posterior lateral thoracotomy]. AB - A case of a primary synchronous lung cancer is presented. Both tumors were removed via a simultaneous both sided posterior lateral thoracotomy. The radical surgical procedure produced respiratory insufficiency resulting in grave adaptation problems and the need to put the patient on a respirator. Rehabilitation allowed the patient to overcome the initial problems allowing light physical work without dyspnea. PMID- 7866325 TI - [Cause of rare pulmonary tumors. Two cases of pulmonary carcinosarcoma]. AB - Two cases of primary pulmonary carcinosarcoma in men, aged 59 and 57 years, have been described. These are 100-th and 101-st descriptions in the world literature, being the second and third in Poland. The preoperative diagnosis of malignant neoplasm of endobronchial tumour was established on the basis of cytologic examination of sputum and specimen from bronchus. While the peripheral tumour was diagnose on the basis of fine needle transthoracic biopsy. The ultimate diagnosis was made by relying on histological examination, as well as after application of monoclonal antibodies. Cytokeratin and vimentin expression were detected in endobronchial neoplasm, but only cytokeratin expression was disclosed in the neoplasm peripherally in the lung parenchyma. The authors focus the attention on the increase, evidenced in the last ten years, of primary malignant and non malignant, uniform and mixed mesenchymal tumours of the lungs, as well as on the relevant new problems and difficulties in microscopic preoperative diagnosis. PMID- 7866326 TI - [Boerhaavea syndrome--diagnostic difficulties]. AB - Two cases are presented in whom a spontaneous tearing of the esophagus was diagnosed. Both were initially treated for pleural empyema and pneumothorax. Late correct diagnosis was the cause of treatment failure. PMID- 7866327 TI - [Moraxella catarrhalis as an important etiologic factor in infection of the lower bronchial tree]. AB - Moraxella catarrhalis in responsible for a considerable number of bronchopulmonary infections in adults, as well as otitis media and sinusitis in children. Many strains of Moraxella catarrhalis produce beta-lactamase and are resistant to many beta-lactam antibiotics. When Moraxella catarrhalis in considered to be a causative organism, the choice for an empiric antimicrobial therapy should be beta-lactamase-resistant antibiotics. PMID- 7866328 TI - [Lung transplantation in cystic fibrosis]. PMID- 7866329 TI - [Paraneoplastic syndromes in lung cancer]. PMID- 7866330 TI - [Use of diagnostic ultrasonography in differentiation of pleural effusion and parietal lesions of the thorax]. PMID- 7866331 TI - [Cardiac arrhythmias, prognosis and sudden death during the stable period of chronic obstructive pulmonary disease]. PMID- 7866332 TI - [Nobel prize in chemistry in 1993]. PMID- 7866333 TI - Proceedings of the 1st Cambridge Peripheral Blood Progenitor Cell Symposium. Cambridge, United Kingdom, July 5-6, 1994. Abstracts. PMID- 7866334 TI - The role of CD8+ T cells in the pathogenesis of atopic asthma. AB - The role of the CD8+ T cells, a specialized subset of T cells, in the pathogenesis of atopic asthmatics is presented on the basis of the latest data. Thus the authors discuss the regulatory role of the CD8+ T cells in the synthesis of IgE, the environmental factors which activate preferentially the CD8+ cells as well as other factors such as histamine, the leukochemoattractant factor, PGE2, IFN gamma and IL-4 which also contribute to the activation of these cells thus demonstrating their role of down-regulating the immune response in asthmatics without the T helper or T cytotoxic. PMID- 7866335 TI - The antioxidative action of fibrinogen and the implications of this effect on platelet aggregation. AB - Purified fibrinogen strongly acts as an antioxidant by inhibiting the chemiluminescent emission developed in vitro, in a cell-free system composed of luminol and hydrogen peroxide. The antioxidative action of fibrinogen depends directly on its concentration, even in the presence of human serum. On the other hand, the platelet aggregation is an important source of oxygen free radicals. These radicals can also be measured by chemiluminescence, when the platelet aggregation is triggered by arachidonic acid. In a platelet suspension, fibrinogen inhibits both aggregation and the associated chemiluminescent emission. A possible correlation between the plasma level of lipid peroxides and fibrinogen was studied in different groups of patients, mostly with cardiovascular diseases and neoplasms. A weak correlation was found only in cardiovascular diseases, in which the tendency of fibrinogen increase could also be interpreted as an antioxidative action of peroxidation restriction, especially in ischemic conditions. In neoplasms, this correlation could not be found, in spite of the high level of fibrinogen associated with a decrease of peroxide formation, a characteristic feature of tumoral growth due to the change of fatty acids nature in the cellular membranes. PMID- 7866336 TI - Study of interrelationship between Zn, Ca and Mg seric concentrations in healthy subjects comparatively with diverse forms of cancer. AB - The interdependence between the serum Zn, Ca, Mg concentrations was studied in a group of healthy subjects comparatively with a group of patients with various form of cancer. It was found that it is significant difference between the control group and the groups of cancer patients, which shows that the carcinogenic processes disturb the concentrations of these metallic ions, not only quantitatively but also the interdependence between them. PMID- 7866337 TI - Plasma protein C and antithrombin III in patients with acute leukemia. AB - When compared to values recorded in the 32 healthy control subjects, plasma protein C activity was found to be significantly decreased in the 29 patients with acute leukemia and especially in those considered to be in a critical condition. On the other hand, plasma antithrombin III activity did not significantly differ from the values noted in control subjects. The concomitantly occurring high plasma fibrinogen levels and low serum cholinesterase activity were highly suggestive for a switch of hepatic protein synthesis towards the production of acute phase proteins. It is therefore considered that in the absence of a consumption coagulopathy, changes affecting plasma protein C and antithrombin III should be related to a modified pattern of hepatic protein synthesis. PMID- 7866338 TI - Treatment with zincum metallicum CH5 in patients with liver cirrhosis. Preliminary study. AB - The zinc, an important enzymatic cofactor, is involved in many metabolic processes. Its deficiency might be due either to malabsorption or to excessive utilization. In the medical literature of the latest 10 years, zinc was considered to play a part in the immune processes. The authors of the present paper intend to study the zinc and immunoglobulin levels in various diseases, i.e., chronic progressive hepatitis, liver cirrhosis (LC), dermatitis, bronchial asthma. This preliminary investigation was carried out in 30 patients with LC in whom serum zinc values were assayed by atomic absorption spectrophotometry and the immunoglobulin levels were determined using the Mancini type simple radial immunodiffusion technique. All these patients presented considerable decrease of serum zinc concentration, the values ranging between 3.06 and 7.65 mumol/l as compared with 19.8 +/- 1.5 mumol/l in the controls, alongside with the increase of immunoglobulins G and M. In the patients treated with Zincum metallicum CH5 it was observed after about 30 days of treatment that the clinical state was considerably improved and IgG and IgM as well as serum zinc had resumed their normal values. This treatment should not be interrupted since in LC, without permanent additional supply, the serum zinc returns rapidly to the initial deficit or even lower. PMID- 7866339 TI - The relationship between the urinary level of some amino acids and the occurrence of metabolic diseases associated with psychic disorders. AB - Assays of the branched chain amino acids, of those with basic character, of phenylalanine and glutamic acid were performed in the 24 hrs urines of 50 patients with psychic disorders, ranging in age from 0 to 20 years, and in 30 normal controls. Similar investigations were carried out in the patients' parents. Abnormal levels of urinary amino acids in some of the adults suggested the existence of mutant genes in one or both parents of one or two descendents with mental handicap. The levels of urinary amino acids correlated with the severity of the predominant psychic manifestations, which were more severe in the cases with a wide deviation from normal of aminoaciduria. PMID- 7866340 TI - Clinical study of the effect of laser therapy in rheumatic degenerative diseases. AB - The effect of a 940-980 nm length wave laser radiation in rheumatic degenerative diseases was studied in 136 patients unresponsive to or with contraindications for antiinflammatory non-steroid therapy. The evolution was clinically estimated using four parameters; pain, muscular contracture, local edema and the impairment of the articular mobility. All patients presented a beneficial evolution appearing gradually during the treatment. The osteoarthritis of the knee, ankle and shoulder evolved worse than the painful back. The painful back presented an improved evolution when it was located at the thoracal level. No adverse reaction was observed during this study. PMID- 7866341 TI - [The effect of salmeterol on aspirin-induced asthma and on smell]. PMID- 7866342 TI - Proceedings of the 2nd annual meeting of the Canadian Society for Exercise Physiology. Hamilton, Ontario, October 26-29, 1994. Abstracts. PMID- 7866343 TI - 1st (GUIDE) Groningen Utrecht Institute for Drug Exploration autumn meeting. Utrecht, The Netherlands, 8 November 1994. Abstracts. PMID- 7866345 TI - Pharmacological meeting. Noordwijkerhout, The Netherlands, 8-9 December 1994. Abstracts. PMID- 7866344 TI - 19th LOF-Symposium on Pharmacognosy and Natural Products Chemistry. Antwerpen, Belgium, 25 November 1994. Abstracts. PMID- 7866346 TI - Detoxification of lipopolysaccharide (LPS) by egg white lysozyme. AB - Recent studies carried out by our group suggest that lysozyme binds to bacterial lipopolysaccharide with a high affinity to produce a complex, and inhibits various biological activities of lipopolysaccharide. Although the basic structure of lipopolysaccharide is independent of the species and strains of Gram-negative bacteria, many structural factors such as O-antigenic polysaccharide, lipid A, substituted groups, and associated molecules, affect the biological activities of lipopolysaccharide. In this study, we prepared lysozyme/lipopolysaccharide complexes using various structures of lipopolysaccharide and compared the activity and physicochemical properties. Native and dansylated lysozyme were found to bind to all tested lipopolysaccharides. The mitogenic activity and TNF production by all tested lipopolysaccharides were significantly reduced by complex formation in vitro. Administration of the complex prepared by various lipopolysaccharides produced significantly less quantities of TNF in the septic shock model. These results suggested that binding of lysozyme to lipopolysaccharide is important for the host both in pathophysiological responses to lipopolysaccharides and in the modification of lipopolysaccharide biological activity. PMID- 7866347 TI - Intercellular adhesion molecule-1 (ICAM-1) and MHC class II on chondrocytes in arthritic joints from pigs experimentally infected with Erysipelothrix rhusiopathiae. AB - This study set out to investigate the in vivo expression and distribution of the porcine homologues of the intercellular adhesion molecule-1 (ICAM-1) and MHC Class II as markers of chondrocyte activation during the development of chronic polyarthritis, which was experimentally induced in Landrace pigs by intra articular injection of Erysipelothrix rhusiopathiae. ICAM-1 was found to be strongly expressed in vivo on chondrocytes and synovial cells in arthritic joints but was not detected in cartilage from unaffected joints. Although the majority of ICAM-1 positive chondrocytes did not co-express MHC Class II, chondrocyte-type cells expressing both molecules were detected in the transition zone as the disease progressed, particularly at 5 months post-infection. At this stage infiltration of CD4+ T lymphocytes into the damaged cartilage was also apparent. ICAM-1 and MHC Class II are not constitutively expressed on porcine chondrocytes but appeared to be induced as arthritis progressed. The detection of these markers in the pig helps to establish the validity of this animal model for immunopathological studies. PMID- 7866348 TI - Urease-mediated destruction of bacteria is specific for Helicobacter urease and results in total cellular disruption. AB - The survival of Helicobacter mustelae, Proteus mirobilis, Escherichia coli and Campylobacter jejuni in the presence of urea and citrate at pH 6.0 was examined. H. mustelae, which has urease activity similar to H. pylori, had a markedly reduced survival, median 2.5% (0-78%) (P < 0.001) when incubated under these conditions. Only 7% of the ammonia produced by H. mustelae urease activity was recovered from the buffer, a similar percentage to that previously reported with H. pylori. None of the other organisms, all of which had lower urease activity, had impaired survival under these conditions. Electron microscopical studies demonstrated extensive structural damage to H. pylori following exposure to urea and citrate at pH 6.0. This structural damage to the organisms makes it unlikely that the low recovery of ammonia was due to retention of ammonia within the bacteria and suggests that the ammonia may have been incorporated into glutamate or other amino acids. Incorporation of ammonia into these compounds would deplete the cell of the key metabolic intermediate alpha-ketoglutarate and could thus explain the mechanism of the urease-dependent destruction of the organism. PMID- 7866349 TI - Studies on the influence of ozone on complement-mediated killing of bacteria. AB - The role of ozone in the susceptibility of clinical isolates of Acinetobacter anitratus and Pseudomonas aeruginosa to serum was investigated. It was found that ozone-treated cells were more susceptible to complement-mediated killing serum. These results suggest that ozone damage or change of cell membrane leads to a more rapid penetration of the membrane attack complex of complement. PMID- 7866350 TI - Guinea pigs prepared with various bacteria and their components to induce a necrotic reaction provoked with muramyldipeptide. AB - Guinea pigs were given a preparatory injection of heat-killed Mycobacterium tuberculosis in a water-in-mineral oil emulsion into the footpads. A provocative injection of muramyldipeptide given 3-8 weeks later into the flanks, caused severe inflammation, with hemorrhage and necrosis and necrosis at the footpads. In this study, we determined the features of the preparatory injection required to prepare the necrotic reaction. Most mycobacteria-related and Gram-negative bacteria were capable of preparing guinea pigs for the necrotic reaction upon provocative injection with muramyldipeptide, whereas Gram-positive bacteria did not. Boivin- and Morrison-type lipopolysaccharides, which have a high content of bacterial protein, induced the susceptibility, whereas Westphal-type lipopolysaccharide, which has a low level of the protein, did not. Moreover, the latter adjuvant-active lipopolysaccharide and muramyldipeptide together with ovalbumin also exerted the activity. The development of delayed-type hypersensitivity to the protein antigen seemed to be important for inducing the necrotic reaction. Mice, rats, rabbits and monkeys were injected in the same way as the guinea pigs. The necrotic reaction occurred in the flanks of the monkeys, but not in the other animals. A similar necrotic reaction also occurred in the flanks of guinea pigs given live BCG cells in phosphate-buffered saline as well as the heat-killed M. tuberculosis in water-in-mineral oil emulsion upon provocative injection with muramyldipeptide. These findings suggested that the induction is associated with the development of delayed-type hypersensitivity to the protein antigen administered in the preparatory injection [corrected]. PMID- 7866351 TI - Reliability of laboratory models in the analysis of TBP2 and other meningococcal antigens. AB - The lack of experimental models suitable for the study of meningococcal pathogenicity led us to investigate if those actually in use (culture in iron restricted media and animal models) provide results comparable with the responses observed in vivo during infection. In this work we studied three invasive strains cultured both in laboratory media and in human plasma, analysing the immune responses elicited in mice against membrane antigens and comparing them with those seen using homologous human convalescent sera. Outer membrane protein profiles observed after culture in plasma were different and more complex than those obtained after growth in laboratory media. Analogous differences were observed in the antigenic profiles, detecting some antigens recognized by human, but not mouse sera, and vice versa. However, the response to one of the major iron-regulated outer membrane antigens, the transferrin binding protein 2 (TBP2), was unaffected by the culture medium or the model, human or mouse, used for the analysis. In conclusion, we have found that results of antigenic analysis change depending on the culture conditions and animal models used. For the meningococcal antigen TBP2, growth in iron-restricted laboratory media and a mouse model provide results which correlate well with those observed using convalescent human serum from individuals recovered from infections. We suggest that careful analysis and evaluation of experimental results and their comparison with in vivo elicited immune responses are essential in order to get accurate extrapolations for experimental vaccine designs. PMID- 7866352 TI - Conservation of the cytotoxin-associated (cagA) gene of Helicobacter pylori and investigation of association with vacuolating-cytotoxin activity and gastroduodenal disease. AB - Polymerase chain reaction (PCR) amplification and DNA hybridization analyses were used to test for the presence of the cytotoxin-associated (cagA) gene in 108 strains of Helicobacter pylori. Fifty-two geographically diverse strains of known vacuolating cytotoxin activity, and 56 recent UK clinical isolates from patients with duodenal ulceration (n = 28) and from healthy individuals who were endoscopically normal (n = 28) were studied. Overall, cagA was detected by PCR in 74 (69%) strains and DNA hybridization provided evidence of gene homologues in a further eight strains. For 96% of the cytotoxin-producing strains and 46% of the non-cytotoxin producing strains, there was a close association either with presence or absence of cagA. At the genomic level, Southern blot DNA hybridization showed that cagA was probably present in a single copy in most of the H. pylori tested, and that HaeIII restriction site variation within and around the gene provided additional markers of diversity for the species. As 40% of the cagA containing strains did not produce an active cytotoxin, and no significant association between cagA presence and DU-disease was observed, we concluded that the presence of the cagA gene in H. pylori could not be used as a single reliable predictor of higher risk patients. PMID- 7866353 TI - Chromosome-mediated resistance of Yersinia enterocolitica serotype O9 to intracellular killing by mouse peritoneal macrophages. AB - The survival of Yersinia enterocolitica serotype O9 within mouse peritoneal macrophages was investigated. To evaluate the role of the virulence plasmid in the resistance to intracellular killing, an isogenic pair of virulent (plasmid bearing) and avirulent (plasmid-less) O9 strains was used. The virulent strain was able to express plasmid-encoded outer membrane proteins and to colonize the Peyer's patches of orally infected mice. When mice were infected intraperitoneally, both strains were recovered at similar rates and over the same time from the peritoneal cavity. When in vitro assays were performed, both strains showed similar resistance to intracellular killing by monolayers of resident and inflammatory peritoneal macrophages. Previous opsonization of bacteria did not modify their survival within macrophage monolayers. We concluded that serotype O9 strains display a chromosome-mediated resistance to intracellular killing by mouse peritoneal macrophages. Moreover, macrophage resistance does not seem to be of importance for virulence of serotype O9 strains in mice. PMID- 7866354 TI - Soluble plasma antigen in experimental Salmonella typhimurium infection in mice. AB - To detect and characterize Salmonella antigen in blood, outbred CF-1 female mice were inoculated intraperitoneally with S. typhimurium LT-2 and blood was assayed by ELISA for Salmonella common structural antigen. Plasma antigen was detectable early in the course of infection and increased in quantity later in the course of illness when animals showed high grade bacteremia and high counts of splenic bacteria. Antigen was associated with a cell-free plasma fraction of blood, passed through filters with cut-offs of 0.2 mu and molecular mass of 1000 kDa, and was enhanced in detectability after heating to 100 degrees C for 15 min. Antigen was concentrated by diluting plasma 1:4 in 0.1 M EDTA, heating to 100 degrees C, and concentrating the supernate with an ultrafiltration membrane with a molecular mass cut-off of 15 kDa. By gel filtration, antigen was associated with a peak at about molecular mass 300 kDa in heated plasma and a peak at about 380 kDa in unheated plasma. These results indicate that murine typhoid infection results in circulating soluble plasma antigen, which is heat-stable with a molecular mass of approximately 300 kDa. PMID- 7866355 TI - Quality of life of people with psychiatric disabilities 1 and 3 years after discharge from hospital. AB - We interviewed 43 clients 1 and 3 years following discharge from a psychiatric rehabilitation programme. The Clients' Quality of Life Interview and Uniform Client Data Instrument examined several domains of clients' life situations. Quality of life measures of living situation, social and community living skills, and recreation improved from 1988 to 1990, and other measures were stable. Findings suggest that clients' living circumstances and functioning continue to improve in the 3 years following discharge from psychiatric hospital. PMID- 7866356 TI - The Spanish version of the Nottingham Health Profile: a review of adaptation and instrument characteristics. AB - The increased interest in measuring health status implies a need for instruments that are appropriate and valid. Adaptation of existing instruments may be a cost effective strategy. In this paper we describe the adaptation into Spanish of the Nottingham Health Profile (NHP), a self-administered perceived health questionnaire developed in the UK. The characteristics of the adapted questionnaire (validity, reliability, and sensitivity to change), as well as current and purposed applications, are discussed. Some of the principles that were applied in the described adaptation process may be useful for similar future research: involving the investigators that developed the original instrument; using a panel of lay individuals in the translation process; testing the characteristics of the adapted instrument by replicating previous studies with the original instrument, and organizing an international group for the development and use of the European versions of the NHP. Adaptation of health status measures is an opportunity for gaining comparability when measuring health, and for learning about cross-cultural differences in health-related quality of life. PMID- 7866357 TI - Subjective well-being in French and American samples: scale development and comparative data. AB - We introduce the English language version of a scale of subjective well-being that has proved reliable, valid, sensitive to change, and well suited to research on clinical populations in France. The internal consistency of both versions exceeds 0.80 and the data suggest that they are equivalent in meaning. In a comparative study of normal samples, American subjects scored significantly higher than French; the difference was greater for women than for men. Young French women in particular had lower scores, a finding interpreted in terms of contemporary socio-economic circumstances. We conclude that the two versions of the scale are useful for both within and cross-national research. PMID- 7866358 TI - Rapid translation of quality of life measures for international clinical trials: avoiding errors in the minimalist approach. AB - There is a growing demand for tools to assess outcomes multinationally for use in international clinical trials. This has been accompanied by the need to produce valid and reliable questionnaires in a multiplicity of languages within a short time frame. We present an eight-step protocol for rapidly translating a quality of life (QOL) questionnaire into multiple languages, and demonstrate the protocol's utility and effectiveness by evaluating the translations for reliability and validity. The rapid translation protocol represents a minimalist approach to QOL questionnaire translation. Although this minimalist approach is not considered a recommended methodology, it may represent a feasible mechanism for questionnaire translation under certain circumstances. Most of the steps were completed in the USA, including a translation and back-translation by bilingual translators who were native speakers in the target-language, a test-retest of the translated instrument on five bilingual respondents to establish language and cultural equivalence and review of the translation by and editorial review board. The translated instrument was performance tested in the target language country on a pilot population of patients to determine its reliability and validity. Based on the findings, the instrument was further refined for use in the clinical trial. PMID- 7866359 TI - The Karnofsky Performance Status Scale re-examined: a cross-validation with the EORTC-C30. AB - A cross-validation of the Karnofsky Performance Status (KPS) and quality of life (QOL) as measured by item 30 of the quality of life questionnaire developed by the European Organization for Research and Treatment of Cancer Study Group (EORTC QLQ-C30) was conducted using ordered logit analysis and prospective data from a continuous sample of 139 lung cancer patients. The QOL is found to be a much broader concept than the KPS, since it likely captures not only physical functioning but also functioning in the non-physical dimensions of social, emotional, and possibly cognitive well-being as well as the level of distress in the physical dimensions of pain, breathing and fatigue. These results suggest that the palliative treatment of advanced cancer and the terminally ill should be guided by a broad concept of well-being that goes beyond one based only on physical functioning. PMID- 7866360 TI - Prepubertal children with short stature have a different perception of their well being and stature than their parents. AB - The well-being of children with short stature has commonly been assessed by questioning the children's parents and teachers. Few studies have included questionnaires completed by the children themselves. The aim of this study to compare how short children and their parent perceive the height and well-being of the child. A total of 80 prepubertal children who were investigated for short stature at the Children's Hospital, Goteborg, Sweden were included in the study. The Silhouette Apperception Technique (SAT) was used to estimate the perception by the child and his/her parents of the child's present stature, as well as their expectations of the child's final stature. The mean ratings of the parents' and children's perception of the child's present stature indicate that both children and parents tend to overestimate it. The mean rating of the children's expectations of final height suggests that the children have high and unrealistic expectations of achieving a tall stature. A visual analogue (VA) scale was used to assess aspects of well-being. Although the children in this study did not seem to have a negative perception of their own well-being, their parents rated the children's well-being lower. The correlation between the ratings of parents and children were comparatively low on both the SAT and the VA scale, indicating that conclusions about how children perceive their height and well-being cannot be based solely on the opinions of proxy respondents such as parents. PMID- 7866361 TI - The Nottingham Health Profile as a measure of quality of life in zoster patients: convergent and discriminant validity. AB - The main symptoms of zoster, a disease caused by the reactivation of the varicella zoster virus (that causes chicken-pox) are: rash, associated with pain, burning, or itching, and pain that outlasts the rash sometimes by months or years. The uncomfortable and long-lasting symptoms of herpes zoster are likely to compromise the patient's quality of life. However, the impact of zoster on health related quality of life has not previously been measured directly. Recent papers have demonstrated the ability of generic measures to discriminate among patients with different clinical symptoms. In this paper, we demonstrate the convergent validity for zoster of a generic measure, the Nottingham Health Profile (NHP), by measuring its correlation with rash progression, pain levels, and pain medications. The discriminant validity of the NHP was demonstrated by its ability to distinguish between different levels of pain severity. The NHP dimensions most highly correlated with the pain measures, were pain (0.42-0.50), energy (0.34 0.38) and sleep (0.32-0.38). The NHP scores in all six dimensions show large differences at different levels of pain severity that are statistically significant. These results demonstrate the NHP's validity as a measure of health related quality of life in zoster patients. PMID- 7866362 TI - Measuring quality of life in hospice patients using a newly developed Hospice Quality of Life Index. AB - The purpose of this study was to evaluate the validity and reliability of the newly developed Hospice Quality of Life Index (HQLI). Sixty-eight patient/caregiver dyads from one hospice were asked to fill out the HQLI on admission and after 3 weeks of hospice care. Hospice experts evaluated the items on the tool to assess content validity. The content validity index (0.83) and the alpha coefficients (r = 0.87 and 0.83) supported the validity and reliability of the HQLI. Item analysis revealed items with which patients were most satisfied and aspects of quality of life that were considered to be most important. PMID- 7866364 TI - Proceedings of Chronic Pain in Society. Lund, Sweden, 17-19 August 1993. PMID- 7866363 TI - A new self-assessment questionnaire to measure well-being in children, particularly those of short stature. AB - The impact of short stature on children is commonly assessed in terms of psychosocial consequences. Proxy respondents and formal behavioural performance tests constitute standard methods in the evaluation of growth hormone therapy in children of short stature. Therefore, a self-administered, short and simple adjective check-list was developed and tested on 342 children of both sexes, aged 9-13 years. Six dimensions covering alertness, self-esteem, mood, elation, stability and vitality were derived after factor analysis. High internal consistency reliability was found for all dimensions. Modest correlations with height, reaching statistical significance for alertness, mood and vitality, were observed. Girls described themselves as having lower self-esteem and vitality than boys, while boys had lower scores for elation. It was concluded that the measure was relevant and potentially useful in children with short stature. PMID- 7866365 TI - Chronic pain--the end of the welfare state? AB - The problem of low back pain has reached epidemic proportions in the industrialized nations. The predicament of back pain is common, 30-40% of our populations from 10-65 years old report such trouble to occur on a monthly basis. In 1-8% this results in work-disabling back pain. Only in very few of these patients can physicians diagnose a definite pathoanatomical cause for the pain. It can be deduced that psychosocial factors, including insurance benefits are of importance for this variation. Sweden, with 100% sickness benefits, has the highest disability rate. Few non-surgical methods have proven effective in rendering the patient better for him to return to work. Even fewer studies demonstrate any benefit from surgery, simple open removal of a proven disc hernia being the only exception. For patients with unproven diagnostic labels such as facet arthritis, degenerative disc disease, internal disc resorption and instability, no evidence exists that any type of surgery is cost-effective. More attention must be paid to illness behaviour by anyone treating chronic low back pain syndromes (> 3 months). Such psychological reactions to an originally nociceptive pain stimulus somewhere in the motion segment, must be elucidated and addressed, before embarking on risky and expensive treatment modalities including surgery. It is time for all of us, politicians as well as physicians, to distinguish what types of support will contribute to our nations' future and which ones will undermine it. Our welfare systems are at stake. PMID- 7866366 TI - The epidemiology of chronic pain in a Swedish rural area. AB - In order to establish basic epidemiological data on chronic pain (duration > 3 months) in a rural population, a survey of pain symptoms was conducted by means of a postal questionnaire. The questionnaire was sent to a random sample (from the population register) of 15% of the population aged 25-74 (n = 1806) in two Swedish primary health care districts. The response rate was 90%. In a follow-up study individuals selected among the responders (neck-shoulder pain, widespread pain and controls without pain; n = 213) were examined and interviewed. They were requestioned about pain symptoms 24 months after the initial survey. Without sex differences 55% of the population had perceived persistent pain for 3 months and 49% for 6 months. Women experienced more multiple localizations of pain and had pain in neck, shoulder, arm and thigh to a greater extent than men. Prevalence of pain increased by age up to 50-59 years for both genders and then slowly decreased. The neck-shoulder area was the most common site of pain (women 32.9%, men 27.5%). Blue-collar workers and employers (including farmers) reported chronic pain to a greater extent than other groups. In 13% of the population, manifest pain problems were associated with reduced functional capacity. Examination of selected pain groups indicated a high proportion of unspecific musculoskeletal symptoms. Diagnosis with definite definitions, explaining the pains, were found in 40% of the individuals. Individuals with widespread pain had a higher pain intensity, more somatic symptoms, were more depressive and had the lowest scores for quality of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866367 TI - The incidence of back pain and headache among Swedish school children. AB - Musculoskeletal pain is exceedingly common in young adults. With the aim of studying these symptoms in schoolchildren, a questionnaire survey was carried out among children 8, 11, 13 and 17 years old. The prevalence of back pain and headaches in 1,245 schoolchildren was studied. Twenty-nine per cent of the students reported back pain and 48% headache. In all age groups studied, both back pain and headaches were more common among girls than boys. Girls also reported more frequent symptoms than boys. In a longitudinal study 471 schoolchildren were asked a second time 2 years later. Nine per cent reported back pain and 30% headache in both surveys. Five per cent reported both back pain and headache on both occasions. Despite the reported symptoms most of the pupils did not report health problems. However, pupils with reported pain on both occasions may constitute a risk group for future chronic pain. There were statistically significant relationships between social, psychological and emotional factors and reported symptoms. No relationship between physical factors and reported symptoms were noted. The observed relationships are not proof of causal relations but did indicate areas of problems which make interventions targeting pupils at risk an appropriate measure. PMID- 7866368 TI - Specified diagnosis in 532 cases of back pain. AB - In the city of Malmo, Sweden, a project was started to improve the rehabilitation of patients with back pain. Among 532 patients with back pain who were on sick leave for an average of 98 days the year preceding the consultation, very few specific diagnoses were made in spite of a thorough clinical and radiological examination. Only five of the patients were cured by surgery. During the same period 103 patients were operated on for disc herniation or nerve root stenosis at the Orthopaedic Department at Malmo General Hospital. Thus the routines for somatic diagnosis of the medical service in Malmo are adequate and an improvement would have very little effect on the expenditures for sick leave and early retirement. As suggested in this paper social and psychological factors are of greater importance in the rehabilitation and we should focus less on the physical problems of the patient. PMID- 7866369 TI - Entering the loop: assessing the contribution of pain clinics in northern Britain. AB - A survey of patients attending ten outpatient pain clinics throughout northern Britain was undertaken to identify opportunities for improving the treatment of pain patients. A short data collection form was designed to obtain information at every patient consultation. The patients were found to be a diverse group, many with complex pain problems. For many patients meaningful diagnoses could not be obtained. The focus of the study was altered to address a selected group of patients: those with neurogenic pain. This group was selected because it was comparatively easy to define, and previous studies suggested that nerve damage pain might not always be well managed. Many patients were found not to have had adequate trials of potentially effective therapies prior to attendance at the pain clinics. Some of these therapies, such as antidepressants and anticonvulsants, could have been prescribed by general practitioners. However, there were also substantial differences between the clinics in the proportion of patients receiving particular therapies. Finally, although many patients had psychological morbidity few were offered psychological assessment and management. These studies have shown that the pain clinics provide a range of therapies which patients are unlikely to receive elsewhere. But there is scope for improvement in the management of patients in pain clinics and efforts are currently being directed towards this. PMID- 7866370 TI - Pain, nerve dysfunction and fatigue in a vibration-exposed population. AB - The long term use of hand-held vibrating tools may cause vasospastic and neuromuscular problems. Symptoms include painful blanching of the fingers at low temperatures, intermittent paresthesia and numbness, impaired dexterity, a tendency to drop tools, and an increasing inability to identify small objects by touch alone. Neurological as well as vasospastic problems are graded according to the Stockholm workshop scales. Accurate and early diagnosis is particularly important (e.g., in vibration-exposed patients presenting a carpal tunnel syndrome, it is necessary to distinguish whether compression of the median nerve occurs at the digital, skin receptor or carpal tunnel levels). A variety of improved diagnostic techniques are discussed. PMID- 7866371 TI - The recurrence of pain after neurosurgical procedures. AB - Various reasons exist for the frequent failure of neurosurgical procedures to control pain. Three main classes of factors are involved in this failure--those relating to the surgeon and the surgery, those dependent on the disease, and those dependent on the nervous system itself. In the first class, technical and conceptual difficulties may explain the recurrence of pain after neurosurgery, including our incomplete understanding of the function of recognized pain pathways, the failure of the surgeon to apply known information, and technical limitations in our ability to carry out neurosurgery. Factors dependent upon the disease itself include alterations in the physical extent of the disease, and in the types of pain caused by it. Factors dependent on the nervous system include nerve and tract regeneration, changes in the anatomy of the CNS in response to both the disease and the neurosurgery, and, importantly, somatotopographic reorganization including the opening of alternative pathways. PMID- 7866372 TI - Chronic pain in society--a case for chronic pain as a dysfunctional state? PMID- 7866373 TI - Pain and suffering: what is the unit? AB - Nonspecific low back pain presents several problems to health care providers. Although the number of patients who are registered as disabled due to low back pain has dramatically increased in recent years, its incidence and severity remain fairly constant. The relationship between perceived backache and subsequent disability is not linear, and other factors may influence a patient's decision to seek help. These factors include the patient's psychological and emotional state, especially his or her past experiences, extant mood and anxiety about anticipated consequences. Physicians should not rely on a simple 'disease model' when treating low back pain but should try to identify the biopsychosocial factors involved and should understand that pain and suffering are not always synonymous. PMID- 7866374 TI - Idiopathic pain and depression. AB - This report summarizes research on the hypothesis that idiopathic chronic pain syndromes and depressive disorders share certain common pathogenetic mechanisms. There is increasing evidence that this may be partly true. Not only do chronic pain syndromes respond to treatment with antidepressants, but there are also striking clinical similarities between these syndromes and depressive syndromes. However, important differences do exist (e.g., the courses of these disorders are usually dissimilar). Family studies show that affective disorders are common in first-degree relatives of patients with idiopathic pain syndromes, but it is impossible to conclude from this that clear-cut genetic factors are of importance. Factors common to both syndromes include common personality traits, shortened rapid eye movements in sleep EEG, hypercortisolaemia and pathological dexamethasone suppression tests, low levels of melatonin in serum and urine and high levels of endorphins and Fraction I in cerebro-spinal fluid. One important common pathogenetic mechanism seems to be disturbances in the serotoninergic system. PMID- 7866375 TI - Logic, truth and language in concepts of pain. AB - Logic and language influence our ideas about the truth of pain, and can alter our understanding of it. Physicians should not tell their patients that there is nothing wrong with them if all their test results are negative, as this denies their patients' experiences of pain. Popular methods of conceptualizing pain may be erroneous. Diagrams of pain or disability are misleading and unhelpful--it is not usually possible to distinguish their components in practice. Giving patients a high or low score for pain behaviour, depression or for health locus of control can influence our views on aetiology in a seriously misleading way. Anyway, aetiological attributions are not always possible from analyses of the experience of pain. The problems of logic and language inherent in assigning pain to emotional causes, in using behavioural approaches, and in defining idiopathic pain and somatization are discussed. The IASP definition of pain is important and useful, provided that it is used appropriately. The recommended version is now 'an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.' PMID- 7866376 TI - Somatization, distress and chronic pain. AB - The two defining features of somatization are numerous self-reported physical symptoms and excessive health care seeking. This may be due to a lowered perceptual threshold for perceiving and reporting bodily symptoms, amplification or misinterpretation of those symptoms, or underlying psychiatric disturbance. Recurrent pain is the most common somatic symptom reported. True somatization disorder is very rare (< 1%) and requires a DSM-III-R diagnosis of at least 13 different physical symptoms which cannot be explained by, or are in gross excess of physical findings, and have caused the patients to seek health care or alter their lifestyles. However, researchers have argued that a spectrum of severity for somatization exists, and this is supported by epidemiological research. Available data also indicate that behavioural interventions may show long-term cost-effectiveness in the management of chronic pain. Chronic pain dysfunction appears to place a disproportionate burden on overall health care expenditure for chronic pain patients. PMID- 7866378 TI - Ischaemic heart disease: disability and costs. AB - Ischaemic heart disease is responsible for a considerable part of chronic pain in society, and is mainly due to angina pectoris. Improvements in pain relief and treatment continue to be developed, and are likely to improve and become cheaper in the future. Prevention is also of great importance for both individuals and society, and is proving cost-effective. However, we have still to learn much about its complex nature. PMID- 7866377 TI - The economic impact of musculoskeletal disorders. AB - Musculoskeletal disorders have a major impact on society in terms of morbidity, long-term disability and economics. As populations increase and age, payment for medical care and indirect costs from loss of earnings will increase. Both rheumatoid arthritis and low back pain have a great economic impact on society, and the costs of these are escalating problems. Statistics are analysed from various studies in the United States and Canada, and these highlight the need for more rational and effective health care management strategies. PMID- 7866379 TI - The probability of recovery and return to work from work disability as a function of time. AB - This paper describes a prospective longitudinal cohort study of musculoskeletal soft tissue pain impairment following a work related injury. It focuses on specific, univariate prognostic factors indicated in previous research studies that might affect the likelihood that injured workers will return to work or remain on work disability at any point in time. These factors include gender, age, return to work attempts and site of injury. Life table analysis was used to model the probability of work disability. The results showed that different disability and return to work patterns emerged for males and females. Males were more likely to return to work; however, females had a higher probability than males of remaining at work once they returned to work. Older workers had the highest probability of being off work any given number of days after injury; were less likely to return to work, and if they did, had a higher probability of becoming disabled again. Efforts to return early to work contributed to a decrease in overall work disability. Workers with low back injuries had a greater likelihood of recurrence compared to injuries at other body sites. PMID- 7866380 TI - Artificial infections of Pneumocystis carinii in the SCID mouse and their use in the in vivo evaluation of antipneumocystis drugs. AB - A model for the in vivo evaluation of antipneumocystis drugs has been developed in SCID mice infected intratracheally with cryopreserved mouse-derived Pneumocystis carinii. The development of a highly reproducible fatal P. carinii pneumonia occurred within 10 weeks (mean survival time +/- SEM = 72.2 +/- 1.2 days). Continuous administration of dexamethasone (2 mg/liter in the drinking water) exacerbated the rate of onset of severe P. carinii pneumonia (mean survival time +/- SEM = 63 +/- 1.3 days) in SCID mice. The number of cysts per g of lung homogenate (homogenate counts) were maximal with an inoculum of 20,000 cysts at 6 weeks post infection. Homogenate counts correlated with infection scores (graded assessments of immunofluorescent cysts on lung impression smears) suggesting that infection scoring accurately and rapidly reflects the severity of P. carinii pneumonia in SCID mice. These studies led to the development of a drug screening protocol in which Pneumocystis-free female SCID mice (20-25 g) were started on dexamethasone 7 days prior to IT inoculation with a single dose of 20,000 cysts. Drugs were evaluated either for: a) prophylaxis (continuously from day 1 post infection) or b) treatment (from day 21 post infection) until day 42 post infection, when all mice were killed and infection scores determined. Co trimoxazole (at 250 mg sulfamethoxazole + 50 mg trimethoprim/kg/day) given in the drinking water was found to be highly effective in both the prophylaxis and treatment of mouse P. carinii pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866381 TI - Cilia-mediated oriented chemokinesis in Tetrahymena thermophila. AB - The role of the cilia in the locomotion ("gliding") of Tetrahymena thermophila in a semi-solid medium has been studied when cells were migrating in gradients of attractant. Video recordings and computer-aided motion analysis of migrating cells and their ciliary activity show that Tetrahymena thermophila migrate by swimming forward in semi-solid methyl cellulose, using their cilia. Ciliary reversals occur at certain intervals and cause a termination ("stop") of cellular migration. Cells with reversed cilia resume forward migration when normal ciliary beating resumes. In gradients of attractants, cells migrating towards the attractant suppress ciliary reversals, which leads to longer runs between stops than in control cells. Cells migrating away from the attractant have a higher frequency of ciliary reversals than the control cells resulting in shorter runs. Stimulated cells adapt to a particular ambient concentration of attractant several times during migration in the gradient. Adaptation is followed by de adaptation, which occurs during the "stop." In the presence of cycloheximide, a strong inhibitor of chemoattraction, the attractant-induced suppression of ciliary reversal is abolished (cells become desensitized to the attractant). It is concluded that Tetrahymena has a short-term memory during adaptation. This is important for the efficiency of migration towards an attractant. PMID- 7866382 TI - Subcellular localization of the enzymes of the arginine dihydrolase pathway in Trichomonas vaginalis and Tritrichomonas foetus. AB - The enzymes of the arginine dihydrolase pathway were demonstrated in Tritrichomonas foetus and their subcellular localization determined for both T. foetus and Trichomonas vaginalis. Ornithine carbamyltransferase (anabolic and catabolic activities), ornithine decarboxylase and carbamate kinase activity were localized predominately (56-80%) in the non sedimentable fraction of both species. A large proportion (35-40%) of the arginine deiminase was, however, recovered in the large granular fraction, and this distribution was unchanged by increasing the ionic strength of the buffer. Upon density gradient centrifugation the particles containing arginine deiminase activity had an isopycnic density of 1.09 g/ml in percoll, and separated from hydrogenosomes (1.18 g/ml) and lysosomes (1.12 g/ml). Arginine deiminase was also the only enzyme of the dihydrolase pathway which demonstrated latency upon treatment of the 1.09 g/ml fraction with non-ionic detergents. The results demonstrate the presence of the arginine dihydrolase pathway in T. foetus and indicate that at least a portion of the arginine deiminase in trichomonads is membrane associated. PMID- 7866383 TI - Characterization of the eyespot regions of "blind" Chlamydomonas mutants after restoration of photophobic responses. AB - Chlamydomonas reinhardtii exhibits photophobic and positive and negative phototactic responses that can be defined for cell populations using computerized cell tracking and motion analysis. Mutants CC-2359 and FN68 are pigment deficient mutants that are blocked in carotenoid synthesis and lack these photo responses. In particular, neither mutant exhibits flash-induced photophobic responses to visible light stimuli to which wild-type gametic cells exhibit a strong response, with several behavioral stages. Upon addition of all-trans retinal to these mutants, the photophobic responses are restored with minor quantitative differences from wild-type populations. Using both light and electron microscopy, we have compared the ultrastructural characteristics of wild-type C. reinhardtii to those of both mutants. As previously described, wild-type cells contain an eyespot consisting of 2-4 layers of pigmented granules encased within thylakoid membranes, located between the distal extremities of the flagellar root. This structure is also visible as an orange-red spot in light microscopy. The photoreceptor is thought to be concentrated in the plasma membrane above the eyespot. The mutant, CC-2359, lacks this eyespot as seen by both light and electron microscopy, even when the photophobic response has been restored. FN68 like mutants studied earlier by Morel-Laurens and Feinlieb and others contain an eyespot which can be seen only by electron microscopy. In FN-68, the eyespot generally has the same dimensions as in wt cells, differing mainly in pigment granule appearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866384 TI - Chilodonella spp. at four fish farms in northern Finland. AB - A total of 4.1% infestation with Chilodonella spp. was found among fish studied in 144 tanks in 1987-1989, representing 14.0% of the tanks in which fish are reared at four salmonid farms in northern Finland. Two species were found, C. hexasticha and C. piscicola, and both occurred on salmon (Salmo salar L.), sea trout [S. trutta m. trutta (L.)] and brown trout [S. t. m. lacustris (L.)]. Variability was observed in the length and width of the C. piscicola specimens and the number of ciliary rows or kineties. Large specimens which had more kineties than average for C. piscicola were found mainly on the skin of salmon aged 1-2 years. The number of kineties in the right ciliary band was found in stepwise logistic regression analysis to be of importance when typing C. piscicola specimens. Fingerlings were found to be more susceptible to Chilodonella infestation than older fish, and mortality varied in the range 2-10% in the course of the epizootics in the three fish species. Most mortality cases were caused by C. hexasticha, occurring mainly on the gills of the fish. Chilodonella piscicola was most often found in salmon and occurred at lower water temperatures than C. hexasticha (mean water temperature when found for the first time being 13 degrees C and 16 degrees C, respectively). PMID- 7866385 TI - The journey of malaria sporozoites in the mosquito salivary gland. AB - The life cycle of malaria parasites in the mosquito vector is completed when the sporozoites infect the salivary gland and are ready to be injected into the vertebrate host. This paper describes the fine structure of the invasive process of mosquito salivary glands by malaria parasites. Plasmodium gallinaceum sporozoites start the invasion process by attaching to and crossing the basal lamina and then penetrating the host plasma membrane of the salivary cells. The penetration process appears to involve the formation of membrane junctions. Once inside the host cells, the sporozoites are seen within vacuoles attached by their anterior end to the vacuolar membrane. Mitochondria surround, and are closely associated with, the invading sporozoites. After the disruption of the membrane vacuole, the parasites traverse the cytoplasm, attach to, and invade the secretory cavity through the apical plasma membrane of the cells. Inside the secretory cavity, sporozoites are seen again inside vacuoles. Upon escaping from these vacuoles, sporozoites are positioned in parallel arrays forming large bundles attached by multilammelar membrane junctions. Several sporozoites are seen around and inside the secretory duct. Except for the penetration of the chitinous salivary duct, our observations have morphologically characterized the entire process of sporozoite passage through the salivary gland. PMID- 7866386 TI - Immunoelectron microscopy of Giardia lamblia cytoskeleton using antibody to acetylated alpha-tubulin. AB - Giardia lamblia trophozoites contain acetylated alpha-tubulin but lack detectable levels of tyrosinolated alpha-tubulin, as demonstrated in immunoblots with monoclonal antibodies specific for these tubulin forms. By immunofluorescence microscopy, acetylated alpha-tubulin is localized in axonemes, median bodies and in the adhesive disk. Post-embeddment immunogold labeling of thin sections of cells was used to evaluate acetylation at the level of individual microtubules by electron microscopy. Cells were fixed with glutaraldehyde and embedded in the acrylic resin LR Gold. Results indicate all microtubules in adhesive disk, axonemes, basal bodies, funis and the median bodies contain acetylated alpha tubulin. Unlike immunofluorescence labeling, all microtubules of the adhesive disk and the funis could be gold labeled. No nonspecific labeling of the cytoplasm or of structures other than microtubules was observed. Acetylated microtubules in G. lamblia do not appear to be a subset of microtubules and acetylation appears uniform along the entire length of individual microtubules. Acetylation and the tyrosinolation state of microtubules in Giardia are discussed in the context of microtubule stability and crosslinked features of the cytoskeleton. PMID- 7866387 TI - Incorporation of fatty acids and amino acids by cultured Pneumocystis carinii. AB - Cultured P. carinii rapidly took up a variety of fatty acids. The relative rates of uptake for four fatty acids were 18:1 >> 16:0 approximately equal to 18:0 approximately equal to 18:2. Fatty acids were primarily incorporated into phospholipids and the uptake process was specifically inhibited by 2.2 and 22 microM primaquine, a concentration having no effect on host cells. Amino acids were also taken up by cultured P. carinii in a primaquine sensitive process. Radiolabeled leucine was incorporated into the major surface glycoprotein of P. carinii. The formation of radioactive P. carinii-specific proteins indicated that the cultured organisms carried out transcription and translation and that the incorporation of amino acids was dependent upon P. carinii rather than rare HEL human embryonic lung cells. The spinner flask culture system provides convenient access to P. carinii for metabolic studies in defined medium for a period of 5-14 days after inoculation. PMID- 7866388 TI - A new rDNA repeat unit in human Giardia. AB - The rDNA repeat unit from a new human Giardia duodenalis strain shows significant differences from the previously reported G. duodenalis rDNA repeat. Twelve base pair changes occurred in 490 bp of the SSrRNA gene and new restriction enzyme sites occurred in the LSrRNA gene. The overall length of the rRNA genes is the same but the spacer is 76 bp longer than previously reported. A boundary within the spacers of the two different rDNA units divides a region of 50% homology near the LSrRNA gene from a region of 80% homology toward the SSrRNA gene. This boundary region includes two copies of a 78 bp repeat. PMID- 7866390 TI - F-actin distribution of Dictyostelium myosin I double mutants. AB - The roles of the myosin I class of mechanoenzymes have been investigated by single and double gene knockout studies in the amoeba Dictyostelium discoideum. Cells lacking different myosin I pairs (myoA-/myoB-, myoB-/myoC-, and myoA-/myoC ) were examined with respect to their cytoskeletal organization. F-actin localization by rhodamine-phalloidin staining of cells indicates that the myoA /myoB-, myoB-/myoC-, and myoA-/myoC- cells appear to redistribute their F-actin more slowly than wild type cells upon adhesion to a substrate. These studies suggest that Dictyostelium myoA, myoB, and myoC may have overlapping roles in maintaining the integrity or organization of the cortical membrane cytoskeleton. PMID- 7866389 TI - Molecular characterization of a cytoplasmic dynein from Dictyostelium. AB - Cytoplasmic dynein is a high molecular weight, microtubule-based mechanochemical ATPase that is believed to provide motive force for a number of intracellular motilities, including transport of membrane-bound organelles. Cytoplasmic dynein also localizes to the mitotic spindles of some organisms and to the kinetochore regions of some condensed chromosomes, where it may play an active role in spindle assembly, spindle position, and/or chromosome movement during cell division. Despite active research efforts from a number of laboratories, little detail is yet available about dynein-based cellular activities. This paper describes our efforts to characterize cytoplasmic dynein from Dictyostelium and to use this protist as a molecular genetic factory to probe structure-function relationships of this molecule. PMID- 7866391 TI - Heterogeneity effects in visual search predicted from the group scanning model. AB - The group scanning model of feature integration theory (Treisman & Gormican, 1988) suggests that subjects search visual displays serially by groups, but process items within each group in parallel. The size of these groups is determined by the discriminability of the targets in the background of distractors. When the target is poorly discriminable, the size of the scanned group will be small, and search will be slow. The model predicts that group size will be smallest when targets of an intermediate value on a perceptual dimension are presented in a heterogeneous background of distractors that have higher and lower values on the same dimension. Experiment 1 demonstrates this effect. Experiment 2 controls for a possible confound of decision complexity in Experiment 1. For simple feature targets, the group scanning model provides a good account of the visual search process. PMID- 7866392 TI - Dissociations of processes in recognition memory: effects of interference and of response speed. AB - Effects on two bases for recognition-memory judgements were examined using a process dissociation procedure (Jacoby, 1991). In three experiments it was found that increasing the length of a study list interfered with conscious recollection but left familiarity in place. Furthermore, an examination of reaction time distributions as well as results from a response-signal procedure showed that familiarity was faster as a basis for recognition judgements than was conscious recollection. However, both bases contributed to performance on the fastest as well as the slowest responses, suggesting that the two processes were acting in parallel. PMID- 7866393 TI - Semantics at a glance: is the right hemisphere special? AB - It is well documented that the left hemisphere is specialized for the processing of alphabetic scripts. However, there have also been repeated suggestions that the right hemisphere is particularly proficient at reading logographs, despite scant empirical support for this proposition. In the present experiment subjects made an odd/even judgement to a single lateralized logograph (an Arabic numeral). The data suggest that the left and right hemispheres are equally efficient at extracting meaning from at least some simple, highly familiar logographs. PMID- 7866394 TI - The international drug control cooperation policy of the European Community: a personal view. AB - The programme of international cooperation of the European Community (EC) in the field of drugs has been in existence since 1987. The scope of the programme is wide and covers, in principle, all aspects of the drug problem in the partner countries. However, interdiction of illicit activities in drug production and trafficking has fallen so far outside the competence of EC, although it will be covered by the European Union once the Maastricht Treaty comes into force. Out of the experience gained in managing the programme, the author suggests that, to be effective, an integrated approach should provide an appropriate place for cooperating more fully in the field of law enforcement. The two priority areas of application of the programme should then be the prevention of drug abuse and the fight against trafficking-two areas which, in fact, tightly reinforce each other. PMID- 7866395 TI - Comparison of three advanced chromatographic techniques for cannabis identification. AB - The development of chromatography technology, with the increasing availability of easier-to-use mass spectrometers combined with gas chromatography (GC), the use of diode-array or programmable variable-wavelength ultraviolet absorption detectors in conjunction with high-performance liquid chromatography (HPLC), and the availability of scanners capable of reading thin-layer chromatography (TLC) plates in the ultraviolet and visible regions, has made for easier, quicker and more positive identification of cannabis samples that standard analytical laboratories are occasionally required to undertake in the effort to combat drug addiction. At laboratories that do not possess the technique of GC combined with mass spectrometry, which provides an irrefutable identification, the following procedure involving HPLC or TLC techniques may be used: identification of the chromatographic peaks corresponding to each of the three main cannabis constituents-cannabidiol (CBD), delta-9-tetrahydrocannabinol (delta-9-THC) and cannabinol (CBN)-by comparison with published data in conjunction with a specific absorption spectrum for each of those constituents obtained between 200 and 300 nm. The collection of the fractions corresponding to the three major cannabinoids at the HPLC system outlet and the cross-checking of their identity in the GC process with flame ionization detection can further corroborate the identification and minimize possible errors due to interference. PMID- 7866396 TI - High dose cocaine use in Bolivia and Peru. AB - Drug-producing countries such as the Andean countries of South America where cocaine is manufactured are confronted by special difficulties associated with the widespread availability of drugs. There have been few detailed reports of patterns of use in relation to the type and severity of cocaine dependence problems within those countries. The present study looks at the patterns of cocaine use in relation to severity of dependence among a clinical sample of South American cocaine users. Information about patterns of cocaine use and severity of dependence was collected from a sample of 68 drug users who were receiving treatment for cocaine problems at treatment centres in Bolivia and Peru. Levels of cocaine consumption were extremely high. The mean daily dose was 16.4 grams. The majority of the users (87 per cent) smoked cocaine in the form of pasta, pitillo or basuco. More than half of the sample reported using cocaine at least 20 times a day. Severity-of-dependence scale scores were high and these are consistent with the frequent and compulsive pattern of use reported within the sample. It is suggested that the more severe cocaine problems reported in South America compared to some western countries may be due to the substantial differences in the amounts of cocaine which are typically ingested. In the Bolivian sample most of the users were taking cocaine in amounts which greatly exceed those usually seen in western countries. PMID- 7866397 TI - Changes in psychological characteristics of drug abusers in a group counselling programme. AB - One hundred male ex-addicts who were provided with an indigenized group counselling programme in after-care service during their two-year compulsory supervision were administered two psychological tests at the beginning and the end of the programme. The tests were eight rating scales on attitudinal and psychological characteristics and the 16 PF questionnaire. t tests show that the successes have changed their attitude towards drug-taking from "favourable" to "unfavourable", and that they have improved in their psychological state and functioning. PMID- 7866398 TI - Volatile substance abuse. AB - Volatile substance abuse (VSA) (glue sniffing, inhalant abuse, solvent abuse), the deliberate inhalation of volatile substances in order to achieve intoxication, has now been reported from most parts of the world, mainly among adolescents, individuals living in remote communities and those whose occupations give ready access to abusable substances. Solvents from contact adhesives, notably toluene, petrol (gasoline), halogenated solvents, volatile hydrocarbons such as those found in cigarette lighter refills, aerosol propellants, halocarbon fire extinguishers, and inhalational anaesthetics may be abused in this way. VSA gives rise to dose-related effects similar to those of other hypnosedatives. Small doses can rapidly lead to euphoria and other disturbances of behaviour similar to those caused by ethanol (alcohol), and may also induce delusions and hallucinations. Higher doses may produce life-threatening effects such as convulsions and coma. Death may ensue indirectly after, for example, inhalation of vomit, or from direct cardiac or central nervous system toxicity. Chronic abuse of toluene-containing products and of chlorinated solvents such as 1,1,1 trichloroethane, for example, can produce severe organ damage, especially in the liver, kidneys, and brain. Drunken behaviour, unexplained listlessness, anorexia and moodiness may result from VSA, especially in children and adolescents. The hair, breath and clothing may smell of solvent, and empty adhesive tubes or other containers, potato crisp bags, cigarette lighter refills, and aerosol spray cans are often found. Toxicological examination of blood and tissue specimens is especially important in confirming a diagnosis of sudden VSA-related death. The development and evaluation of strategies for the treatment of chronic abusers and for prevention are major challenges for the future. PMID- 7866399 TI - Fifty years of development of opium characterization methods. AB - In view of the recent call by the Sub-Commission on Illicit Drug Traffic and Related Matters in the Near and Middle East, for the "development of mechanisms to identify, with more precision and through laboratory analysis, the sources of opium seized from the illicit traffic" [1], the present paper reviews the rationale and preconditions for any practical and reliable characterization and origin-correlated classification of opium. In that context, the results of the early international efforts under the aegis of the United Nations from 1951 to 1967, as well as the rather sporadic investigations in this direction since 1968, are described. Finally, it is demonstrated that in spite of the application of modern computer-based technology, the main obstacle to comprehensive opium characterization and typology is still the lack of an extensive reference collection of opium samples of known origin. PMID- 7866400 TI - Transnational criminal organizations and drug trafficking. AB - Transnational criminal organizations, particularly drug-trafficking organizations, operate unrestricted across international borders. They are very similar in kind to legitimate transnational corporations in structure, strength, size, geographical range and scope of their operations. Above all other features they engage in unregulated forms of capitalist enterprise. To fully understand transnational criminal organizations it is necessary to examine them as organizations responding to economic opportunities and focus on the factors that influence their emergence. Those factors can be understood as a result of the confluence of opportunities, pressures, incentives and resources at the global and national level. The present article identifies the key environmental factors relevant to the emergence of transnational criminal organizations, and explores the intrinsic relationship between those organizations, their home States and host States. It is those conditions which not only give rise to transnational criminal organizations, but also help to sustain them. PMID- 7866401 TI - Molecular genetics of metachromatic leukodystrophy. AB - Metachromatic leukodystrophy is an autosomal recessive inherited lysosomal storage disease. It can be caused by mutations in two different genes, the arylsulfatase A and the prosaposin gene. These genes encode two proteins that are needed for the proper degradation of cerebroside sulfate, a glycolipid mainly found in the myelin membranes. Deficiency of arylsulfatase A or of a proteolytic product of prosaposin leads to the accumulation of cerebroside sulfate, which causes a lethal progressive demyelination. Mutations in the arylsulfatase A gene are far more frequent than those of the prosaposin gene. So far 31 amino acid substitutions, one nonsense mutation, three small deletions, three splice donor site mutations, and one combined missense/splice donor site mutation have been identified in the arylsulfatase A gene. Two of these mutant alleles are frequent, accounting for about one-half of all mutant alleles, whereas the remainder are heterogeneous. Amino acid substitutions cluster in exons 2 and 3, a region that shows a high degree of conservation among sulfatases of different function and origin. Different mutations are associated with phenotypes of different severity, but there is a remarkable variability of severity when patients with identical genotypes are compared. Demonstration of an arylsulfatase A deficiency is not a proof of metachromatic leukodystrophy, since a substantial deficiency without any clinical consequences is frequent in the general population. This deficiency is caused by an arylsulfatase A allele, which due to certain mutations encodes greatly reduced amounts of functional enzyme. However, these amounts are sufficient to sustain a normal phenotype. In the diagnosis and genetic counseling, these deficiencies must be differentiated from those causing metachromatic leukodystrophy. So far only six patients with mutations in the prosaposin gene have been described, in which three defective alleles two with amino acid substitutions and one with a 33-bp insertion have been identified. PMID- 7866402 TI - Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene. AB - Acute intermittent porphyria (AIP) is an autosomal dominant inborn error of metabolism that results from the half-normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase (HMB-synthase). AIP is an ecogenetic condition, with life-threatening acute attacks precipitated by various factors including drugs, alcohol, fasting, and certain hormones. Biochemical diagnosis is problematic and the identification of mutations in the HMB-synthase gene provides accurate detection of presymptomatic heterozygotes, permitting avoidance of the acute precipitating factors. Two HMB-synthase isozymes are encoded by the HMB-synthase gene: one unique to erythroid cells and the other a housekeeping isozyme present in all cells. These two isozymes arise from a single gene by alternative splicing. The recent isolation of the cDNAs and entire genomic sequence encoding the HMB-synthase isozymes has facilitated the detection of diagnostically useful intragenic polymorphisms and disease-causing mutations. Of the 36 mutations identified to date, most caused the classic form of AIP. These mutations included small deletions and insertions, point mutations and RNA splice junction alterations and resulted in the half-normal activity of both the erythroid-specific and housekeeping isozymes. Most AIP mutations were private; however, certain mutations were frequently found in Dutch (R116W) and Swedish (W198X) AIP families. A variant form of AIP, in which patients have normal erythroid activity, but half-normal activity of the housekeeping isozyme, resulted from two mutations at the exon 1/intron 1 boundary, each altering splicing of the hepatic-specific transcript. In addition, 10 polymorphisms in the HMB-synthase gene have been identified that are useful for the diagnosis of presymptomatic AIP heterozygotes in families whose specific mutations have not been determined. PMID- 7866403 TI - Characterization of two novel adenomatous polyposis coli (APC) gene mutations in patients with familial adenomatous polyposis (FAP). AB - Patients with Familial Adenomatous Polyposis (FAP) manifest numerous colorectal adenomas as well as benign and malignant extra-colonic lesions. Adenomatous polyposis coli (APC) gene mutations are the underlying genetic defect in FAP. We analyzed germline DNA of 81 unrelated FAP patients and evaluated correlation of APC mutation genotype and clinical phenotype. Germline APC mutations were identified in 18 FAP patients including two novel 2 bp deletions at APC codons 1067 and 1259. FAP patients were screened for hypertrophic ocular fundus lesions, desmoids and peri-ampullary adenomas. As reported previously (Olshwang et al 1993b), a positive correlation for the frequency of retinal lesions and germline APC mutation was observed among all FAP patients except one. No significant correlation was observed for APC mutation genotype and the occurrence of desmoids and peri-ampullary adenomas. Genetic factors contributing to familial segregation of these lesions need further investigation. PMID- 7866404 TI - Autosomal dominant spondylarthropathy due to a type II procollagen gene (COL2A1) point mutation. AB - Osteoarthrosis represents a very common disease with heterogeneous etiology. In some pedigrees linkage of the condition with the type II collagen gene (COL2A1) has been established, but information on the underlying gene defect is still incomplete as only one mutation causing this phenotype has been identified. We analyzed the COL2A1 gene in a 27-year-old woman and her 47-year-old mother presenting with severe premature osteoarthrosis and X-ray signs compatible with mild spondyloepiphyseal dysplasia. Examination of the complete gene in both patients was done by amplification of all 54 exons, screening of the PCR products by SSCP-analysis, and subsequent sequencing. In mother and daughter a G to A transition at the 5'-end of exon 21 was detected, leading to a substitution of serine for glycine at position 274 of the triple helical domain. The mutation was not present in unaffected family members or in healthy control individuals. The autosomal dominant spondylarthropathies may represent the less severe entities of the clinical spectrum of type II collagenopathies. PMID- 7866405 TI - Mutation analysis of Jewish Hunter patients in Israel. AB - We have performed molecular and mutation analyses on 14 unrelated Israeli Hunter families and have identified the IDS mutation in 8 of them. Three unrelated Ashkenazi patients had the same previously reported mutation (1246 C-->T). Based on the haplotypes of the mutation-bearing chromosomes, we concluded that this is a recurrent mutation. In two patients, we identified a deletion spanning exons V VII. Three novel mutations were observed in different patients: L410P, 717de14, and 244de13. In addition, the silent mutation (562 C-->T) was observed in one patient. PMID- 7866406 TI - Mutation analysis for cystic fibrosis to determine carrier status in 167 sperm donors from the Nebraska Genetic Semen Bank. AB - Cystic fibrosis is the most common autosomal recessive disorder in Caucasian populations, with an approximate frequency of 1/2500 live births and a carrier frequency of 1/25. Due to the high rate of predicted carriers (> 63,000) in the Nebraska population (1990 U.S. Census = 1,578,358), we analyzed sperm DNA obtained from semen donors at the University of Nebraska Genetic Semen Bank for eight of the more common mutations to determine the frequency and diversity in our population. The subjects included 167 semen donors (31 normal healthy donors, 56 infertility patients, 21 prevasectomy patients, and 59 prechemotherapy or preradiation cancer patients). The mutations analyzed included delta F508, R117H, G542X, S549R/N, G551D, R553X, R560T, and W1282X. Analyses were performed using PCR amplified products that were analyzed using polyacrylamide gel electrophoresis, slot blot, and restriction endonuclease digestion. These results were correlated with results from the clinical semen analyses and selected clinical parameters. Results for the total donor population studied showed that the delta F508 mutation was present in 8/167 (4.8%) donors, the R117H mutation was present in 4/167 (2.4%) donors and the G542X mutation was present in 1/167 (0.6%) donors. The observed number of carriers from this population, 13/167 (7.8%), was significantly greater (P = 0.02) than that expected assuming a carrier frequency of 1/25. The excess of carriers was restricted to the subgroup of infertility patients. This suggests that CF carriers may be at higher risk for infertility than the general population. PMID- 7866407 TI - FH-Sydney 1 and 2: two novel frameshift mutations in exon 10 of the low-density lipoprotein receptor gene detected by heteroduplex formation. AB - We report two novel frameshift mutations in exon 10 of the low-density lipoprotein receptor gene that lead to familial hypercholesterolemia in separate lineages. The lesions, FH-Sydney 1 and FH-Sydney 2, were detected by a modified heteroduplex analysis of exon-specific polymerase chain reaction (PCR) amplified DNA, and characterized at the molecular level by sequencing. Restriction enzyme digestion of PCR amplified DNA confirmed the presence of the mutant alleles in affected family members and their absence in nonaffected family members in both lineages. FH-Sydney 1 is a 4-bp duplication at position 1373, while FH-Sydney 2 is a 2-bp deletion at position 1478. The predicted result of both mutations is the premature truncation of the receptor at stop codons generated downstream of the mutations. Neither mutation was detected in a survey of 54 unrelated familial hypercholesterolemia patients. PMID- 7866408 TI - A robotics-assisted procedure for large scale cystic fibrosis mutation analysis. AB - We describe a convenient, efficient, semiautomated protocol for assaying large numbers of DNA samples for over 20 mutations causing cystic fibrosis. The protocol uses the following: (1) a programmable robotic workstation to perform rapid pipetting and dot-blotting operations, (2) an allele-specific oligonucleotide hybridization in a single water bath without correcting for G+C content of oligonucleotides, and (3) a combinatorial system that allows direct determination of the genotype for more frequent mutations. We have used this system routinely for 16 months for carrier detection and for diagnosis of cystic fibrosis. The method can be readily applied to any combination of allele-specific oligonucleotide assays whether for multiple alleles at one locus or for a few alleles at multiple loci. PMID- 7866409 TI - Mutation at the catalytic site (M519V) in glycogen storage disease type II (Pompe disease). PMID- 7866410 TI - Marked zinc activation of ester hydrolysis by a mutation, 67-His (CAT) to Arg (CGT), in the active site of human carbonic anhydrase I. PMID- 7866411 TI - Phenylketonuria in southern Poland: a new splice mutation in intron 9 at the PAH locus. PMID- 7866412 TI - Childhood sexual, physical, and psychological abuse and their relationship to comorbid psychopathology in bulimia nervosa. AB - We examined the relationship between childhood sexual, physical, psychological, and "multiple" abuse (i.e., abuse in more than one form) and comorbid Axis I and personality psychopathology among women with a lifetime history of bulimia nervosa (BN group; n =s 80) and a control group of noneating-disordered women (n = 40). Subjects were recruited primarily by newspaper advertisement. They participated in structured clinical interviews for diagnosis of Axis I and personality pathology, and they completed child abuse questionnaires in the interview setting. At odds with prediction, child abuse in various forms was not associated with the presence of lifetime comorbid Axis I disorders in general (i.e., 1 or more) or disorder classes in particular (mood, alcohol/substance use, anxiety) among BN subjects, although sexual, psychological, and multiple abuse were associated with the diagnosis of a higher total number of Axis I conditions. A history of psychological and multiple abuse (but not physical or sexual abuse alone) among BN subjects was strongly associated with the presence of personality disorder diagnoses, especially those in the "anxious-fearful" cluster (Cluster C). Finally, we found that when a personality disorder was present in addition to the Axis I conditions in question, significant relationships emerged between abuse and Axis I pathology, particularly for psychological and multiple abuse. In general, control group findings were in accord with BN group findings, indicating that our findings were not specific to eating-disordered women. Our results suggest that childhood abuse, particularly psychological abuse and abuse in multiple forms, increase the likelihood of lifetime comorbid Axis I disorders and personality pathology among bulimic patients. Eating-disordered women with a history of child abuse may thus represent a subgroup of patients requiring especially intensive intervention. PMID- 7866413 TI - Sexual orientation as a factor in risk for binge eating and bulimia nervosa: a review. AB - Research on binge eating and bulimia nervosa among lesbians and gay men is reviewed. The thesis that the different value pot on physical appearance in these groups may function as a mediator of risk for eating problems is considered. Studies indicate that gay men focus on their appearance more than heterosexual men and may be at higher risk. Lesbians, who are arguably less invested in societal norms of attractiveness, may be at lower risk than heterosexual women, but the findings are mixed. Implications for conceptual models of risk for bulimia nervosa, and for awareness of lesbian and gay experiences by therapists, are discussed. PMID- 7866414 TI - Diagnoses of eating or dieting disorders: what may we learn from past mistakes? AB - A brief history of a patient is given and an attempt is made to reconcile the clinical realities she presents with the various diagnostic criteria that have been proposed for eating disorders. Despite much deliberation and many formulations, no scheme fully encompasses her not-uncommon problem. Rather than tinker yet again with the criteria for the syndromes of anorexia and bulimia nervosa, or introduce yet another new condition such as binge eating disorder, the authors suggest a unitary approach to diagnosis. Emphasis should be placed on the preoccupation with weight loss, the illness should be conceptualized as a dieting disorder rather than an eating disorder, and patient status should be accorded only when the disturbance results in significant psychological or physical ill-effects. The term anorexia nervosa should be retained for such cases, and all anorexia nervosa patients should be categorized on three parameters, viz: their current state of nutrition; the presence or absence of significant purging behaviors; and whether or not they have binge eating episodes. PMID- 7866415 TI - Assessment of eating disorders: interview or self-report questionnaire? AB - A detailed comparison was made of two methods for assessing the features of eating disorders. An investigator-based interview was compared with a self-report questionnaire based directly on that interview. A number of important discrepancies emerged. Although the two measures performed similarly with respect to the assessment of unambiguous behavioral features such as self-induced vomiting and dieting, the self-report questionnaire generated higher scores than the interview when assessing more complex features such as binge eating and concerns about shape. Both methods underestimated body weight. PMID- 7866416 TI - An examination of the internal consistency and factor structure of the eating disorder inventory-2 in a clinical sample. AB - We examined the internal consistency and factor structure of the newly revised version of the Eating Disorder Inventory (EDI), with particular emphasis on the examination of the three new provisional scales: Asceticism, Impulse Regulation, and Social Insecurity. Subjects were 300 women who were seeking treatment at a residential treatment facility for women with eating disorders. Chronbach's alphas ranged from .80 to .91 for the eight original scales whereas coefficients for the three new scales were all less than .80, the criterion stated as being necessary for inclusion in the test. Item-total correlations were also substantially lower for the three new scales. The results of principal components analyses with orthogonal rotation supported the factor structure of the original 64-item EDI, but not the three additional scales. These data generally supported the reliability and factor structure of the original eight scales but did not support the reliability or validity of the three provisional scales. PMID- 7866417 TI - Convergent validity of the eating disorder inventory and the anorexia nervosa inventory for self-rating in an Austrian nonclinical population. AB - This study assesses the convergent and divergent validity of the Eating Disorder Inventory (EDI--German version) and the Anorexia Nervosa Inventory for Self Rating (ANIS) in a German-speaking nonclinical population. One hundred fifty-five female and 224 male Austrian medical students were surveyed. Validity was studied at a dimensional level, separately for both sexes, by correlating with conceptually related as well as distinct scales. These instruments included the General Health Questionnaire (GHQ). The intercorrelation coefficients of the EDI and the ANIS were similar to the original samples. In women, the convergent validity of the EDI and the ANIS was confirmed, especially for the subscales measuring the specific psychopathology (r = .43 to .84) and for ineffectiveness/feelings of inadequacy (r = .63). The EDI subscales Maturity Fears and Interpersonal Distrust and the ANIS subscales Obsessive-Compulsive Traits and Sexual Anxiety address traits not included in the other test and these showed divergent validity. Divergent validity of the ANIS and to a lesser degree the EDI with the GHQ was established. Both tests can be equally recommended for female subjects. In males however, the validity indices of both tests were generally lower and convergent and divergent validity was not established. PMID- 7866418 TI - Towards the prevention of dieting-induced disorders: modifying negative food- and body-related attitudes. AB - This study investigated the extent to which negative attitudes that focus on the body and on eating could be modified within the context of a group discussion about how other young women's attitudes might be changed. The findings suggest that facilitated group discussion would be a useful tool for changing attitudes and behavioral intention in a preventive intervention aimed towards dieting related disorders. PMID- 7866419 TI - Self-help for bulimia nervosa: a preliminary report. AB - Eighteen patients with DSM-III-R bulimia nervosa were treated by providing them with supervision in the use of a self-help manual based on the cognitive behavioral treatment for the disorder. The patients were assessed before beginning the self-help program, and again 4 to 6 months later, using standardized measures of psychopathology. The findings were encouraging. At follow-up one half of the patients had ceased bulimic episodes and self-induced vomiting, and most of the remainder had made significant improvements. These preliminary findings, together with related published work, suggest that supervised self-help might be an appropriate first line treatment for patients with bulimia nervosa and that for many patients it could be sufficient. PMID- 7866420 TI - Therapeutic alliance on an inpatient unit for eating disorders. AB - The therapeutic alliance as measured by the Working Alliance Inventory was examined on an inpatient unit for eating disorders. Unit staff and patients (n = 33) admitted within a 2-year period completed the rating scales at 3 weeks after admission and again at 8 weeks. Patients who remained in the program (n = 21) perceived the therapeutic alliance with staff to be significantly stronger than patients who left the program (n = 10). The perception of the alliance strengthened over time for patients while staff perceptions did not. Little correlation was observed between staff and patient perceptions of the alliance. The findings suggest that patient perception of the alliance may be a critical factor in the decision to remain in the treatment program. It is argued that helping a patient feel involved in a structured program presents a particular challenge to staff. PMID- 7866421 TI - Anorexia nervosa in an adolescent with early profound deafness. AB - This paper reports a case of anorexia nervosa in a 15-year-old schoolgirl who had been profoundly deaf since birth. She was admitted to a specialized eating disorders unit following a dramatic reduction in her weight. Her deafness and limited communication skills posed significant problems with regard to her overall management on the unit. Her clinical presentation and difficulties in management are presented. PMID- 7866422 TI - 12th World Congress on Endourology and SWL 8th annual Frontiers in Endourology, 10th Basic Research Symposium. St. Louis, Missouri, December 2-6, 1994. Abstracts. PMID- 7866423 TI - Update on bladder smooth-muscle physiology. AB - The urinary bladder responds to distension induced by a number of different stresses with rapid and substantial increases in bladder mass and concomitant alterations in the contractile responses to neuronal stimulation, pharmacological simulation by autonomic agonists, and membrane depolarization. Furosemide, sucrose, or diabetes-induced diuresis, as well as outlet obstruction and overdistension all produce similar effects on the bladder. Accompanying the increases in bladder mass and contractile changes are increases in DNA synthesis and [3H]-thymidine uptake. Autoradiographic studies have localized the increased DNA synthesis following bladder distension initially to the urothelium, followed by slower increases in labelling of the lamina propria and extramural connective tissue. The net result of these compartmental differences in DNA synthesis is a reorganization of the structural relationships between smooth-muscle cells, the connective-tissue matrix, and the extrinsic connective-tissue lamina. This may contribute to the functional changes which occur after severe overdistension. Increases in the expression of heat-shock protein-70, basic fibroblast growth factor, N-ras, and c-myc, and decreases in transforming growth factor-beta occurred acutely after obstruction, suggesting that these changes may play a role in obstruction-induced bladder hypertrophy. Removal of the obstruction induces apoptosis of urothelial and connective tissue elements in the bladder, accompanied by increases in transforming growth factor-beta and decreases in basic fibroblast growth factor genes, and a reversal of the bladder dysfunction. Therefore the bladder hyperplasia after outlet obstruction and the regression following removal of the obstruction seem to be directly opposing processes governed by gene expression. PMID- 7866424 TI - Electrophysiological methods in smooth-muscle physiology. Corpus cavernosum in vitro. AB - The variety of the electrophysiological and mechanical properties of smooth muscle is abundant. In different organs they have different properties and also the orientation of the muscle layers can play a prominent role. Additionally, great species differences exist and some types of animal studies can be completely irrelevant for human physiology. The classic method for electrophysiologic studies of smooth muscle activity is the use of impaled glass microelectrodes. Also extracellular electrodes can be used but due to the method applied, only measurements of the changes in the true membrane potential can be obtained. Another approach is the so-called sucrose gap method which allows, in principle, access to the real membrane potential; due to methodological problems it is now rarely used. With corporal tissue, electrical measurements can be obtained with extracellular electrodes and, concomitantly, also measurements of the mechanical activity are possible. Spontaneous mechanical activity of isolated strips of rabbit corpus cavernosum is characterized by phasic contractions with a frequency of 6-30 min-1, accompanied by the extracellularly measured fluctuations of the membrane potential. Stimulation of the tissue with tetraethylammonium chloride (10 mmol/l) and noradrenaline (10(-5) mol/l) produced strong tonically appearing contractions, which were characterized by a relative electrical silence. Additional application of the nitric oxide donor 3-morpholino-syndominin (SIN-1, 5 X 10(-5) mol/l) relaxed the tissue and revealed phasic mechanical activity with associated electrical activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866425 TI - Basic experimental studies on corpus cavernosum electromyography and smooth muscle electromyography of the urinary bladder. AB - In contrast to the extensive work on in vitro experiments for elucidation of the electrical properties of smooth musculature, the acquisition of knowledge on electrical signal behaviour from smooth-muscle cells in an in vivo situation remains very limited and rare. Smooth-muscle electromyographic recording from the smooth musculature of the genitourinary tract, in particular from the penile cavernous bodies and the urinary bladder, has recently become one of the most interesting issues in both impotence research as well as neurophysiological assessment of the urinary bladder. However, the inadequate available data on corpus cavernosum and EMG recordings remains controversial due to the significant discrepancy between basic physiology of the smooth musculature, technical prerequisites and the expected clinical impact from the smooth-muscle EMG of genitourinary organs. This article is an attempt to describe the fundamentals of smooth-muscle EMG signal behaviour and the technical prerequisites for data acquisition and analysis of electrical activity from smooth-muscle cells of the cavernous bodies and urinary bladder. A description is given of the technical aspects, including methodology and interpretation of the recorded data, and also of the possible interference by artefacts (endogeneous and exogeneous) that might limit the clinical relevance of this encouraging method. The advantages, pitfalls and limitations of online analogous data registration and the possibility of computer-assisted smooth-muscle electrical activity recording and analysis are demonstrated by basic in vivo studies on cavernous bodies and also the detrusor muscle. PMID- 7866426 TI - Characterization of cyclic nucleotide phosphodiesterase isoenzymes in the human ureter and their functional role in vitro. AB - An increase in cyclic nucleotide monophosphate levels is suggested to play a prominent role in mediating smooth-muscle relaxation. Cyclic nucleotide phosphodiesterase (PDE) influences smooth-muscle tone by decreasing the level of cyclic nucleotides. At present, five different families of isoenzymes of PDE exist that show a distinct species- and organ-specific distribution. Our study was done to evaluate the existence of specific PDE isoenzymes and its functional role in human ureteral tissue. Normal ureteral tissue was homogenized and centrifuged and the supernatant fraction was separated using anioin-exchange diethylaminoethyl (DEAE)-Sephacel chromatography. A PDE assay was then performed and the peak fractions were added to different specific PDE activators and inhibitors. In vitro, longitudinal ureteral strips were precontracted and different selective and non-selective PDE inhibitors were added incremently. Three different PDE isoenzymes were characterized: PDE I (calmodulin-sensitive), PDE II (cGMP-stimulated), and PDE IV (cAMP-specific). All PDE inhibitors relaxed the strips dose-dependently, with the 50% effective concentrations (EC50) being 30 microM for papaverine, 40 microM for zaprinast, 25 microM for quazinone, and 0.1 microM for rolipram. The ureter-relaxing effect of the PDE IV inhibitor at low concentrations, combined with its low-level effect on the systemic circulatory parameters, may open the possibility of using selective PDE IV inhibitors in the treatment of ureteral colics or for ureteral stone passage. PMID- 7866428 TI - Differential interaction of the dual alpha tropomyosin/N5 enhancer with multiple DNA binding proteins: N5 is a putative novel z-ZIP DNA binding protein. AB - The alpha tropomyosin (TM)/N5 enhancer is an SV40-like mammalian enhancer comprised of a 99 bp repeat with modular cis-acting regulatory elements exhibiting apparent hierarchical organization. The enhancer differentially regulates the alpha TM and N5 transcription units which exhibit distinct tissue specific expression patterns and interacts with multiple myotube-associated nuclear DNA binding proteins that varied in size and amount. To further characterize the interaction with multiple myotube nuclear factors, comparative southwestern blot analyses were done with a panel of strategic DNA probes representative of modular enhancer sequences in the alpha TM/N5 enhancer and respective alpha TM and N5 promoter regions. Results demonstrate that multiple DNA binding proteins, which vary in size and amount, can interact with a particular enhancer modular sequence (delimited to 18 bp- to 38 bp-long); and that likewise, a DNA binding protein can bind specifically to different DNA enhancer modular sequences with apparent different affinities. Results also demonstrate DNA binding proteins that differentially bind to both enhancer modular sequences and respective promoter regions supporting a putative parsimonious mechanism for the approximation of enhancer and promoter elements as an alternative to the multi-protein stereospecific enhancer complex. Cogent to this interesting "head to head"/shared enhancer gene arrangement, we investigated the primary structure of the "other" transcription unit, N5. Nucleotide sequence analysis of the N5 cDNA reveals that it is a putative DNA binding protein representing a new structural class of transcription factors exhibiting a novel combinatorial motif: single zinc finger (DNA-binding)-leucine zipper (dimerization)--making it a z-ZIP instead of a b-ZIP (basic region/leucine zipper) protein. PMID- 7866427 TI - Regulation of actomyosin and contraction in smooth muscle. AB - Unlike striated muscle cells, smooth muscle cells do not have an organized sarcomeric structure. However, all smooth muscle cells contain the contractile proteins, myosin, actin, and tropomyosin. Polymorphism of the myosin heavy chain exists in smooth muscle cells. Two myosin heavy chain (MHC) isoforms, SM1 (204 kDa) and SM2 (200 kDa), are present in smooth muscle cells; however, their ratios vary in smooth muscles from different sources. The hypertrophy of the urinary bladder induced by partial outlet obstruction in rabbits is associated with an alteration of the SM1-to-SM2 ratio from 1:3 to 1:1. Both heavy chains react with polyclonal antibody against smooth muscle myosin; however, antibody prepared against a peptide from the C-terminal region of the SM2 heavy chain cross-reacts only with the SM2 heavy chain. Removal of the obstruction reverses the bladder to normal mass with a concomitant change in the SM1-to-SM2 ratio back to 1:3. The expression of the SM1 mRNA is increased in response to obstruction-induced hypertrophy, and it also returns to normal upon removal of the obstruction. Urinary bladder smooth muscle contains predominantly gamma-actin. Obstruction induced hypertrophy of the bladder smooth muscle is associated with an increase in the gamma-actin at both protein and mRNA levels. The beta-non-muscle actin is decreased and the alpha-smooth muscle actin is unchanged in response to obstruction-induced bladder hypertrophy. Contraction of all smooth muscles involves similar mechanisms. This review describes our current understanding of the mechanisms regulating contraction of the smooth muscle of the urinary bladder. PMID- 7866429 TI - The expression and processing of human beta-amyloid peptide precursors in Saccharomyces cerevisiae: evidence for a novel endopeptidase in the yeast secretory system. AB - In mammalian cells, the transmembrane beta-amyloid peptide precursor (beta-APP) undergoes a complex series of alternative proteolytic processing steps that result in the secretion of varying proportions of its extra-cellular domain (protease nexin II) and beta-amyloid peptide. The protein is also reinternalized and degraded in the endosomal-lysosomal system. The relative efficiencies of these competing processes determine the yield of beta-amyloid peptide. Several proteases have been implicated in this complex processing pathway, although none has been identified to date. The yeast secretory system contains proteases homologous to mammalian pro-hormone convertases and is susceptible to genetic manipulation. We therefore investigated the expression and processing of the beta amyloid peptide precursors (beta-APP-695 and beta-APP-751) in Saccharomyces cerevisiae transformed with human beta-APP cDNA's. beta-APP (695 or 751) cDNA either with its authentic signal sequence or the yeast-derived prepro-alpha factor leader, was inserted into a glucose-regulated expression vector and transfected into a protease-deficient yeast strain. In all instances, expression of beta-APP was about 1% of total protein. Protease protection studies indicated that either the natural human signal sequence or the alpha-factor leader sequence targetted beta-APP to the endoplasmic reticulum and inserted it with the amino terminal domain in the lumen. All of the beta-APP fused to the alpha-factor leader proceeded to the trans-Golgi, where Kex2 endopeptidase removed the leader and released the normal amino-terminus of beta-APP. About one-half of the beta APP was also cleaved at the "alpha-secretase" site in the middle of the beta peptide sequence, 12 residues before the membrane-spanning sequence. A fraction of the alpha-secretase-cleaved beta-APP appeared in the culture medium; however, most of it associated with the exterior of the cells. The carboxyl-terminal fragments formed by cleavage at the alpha-secretase site accumulated in the membranes. Other proteolytic processes generated membrane-associated carboxyl terminal fragments that also resembled those found in mammalian cells. These results indicate that the secretory system of S. cerevisiae possesses proteases with specificities similar to the mammalian enzymes that process beta-APP. PMID- 7866430 TI - Two distinct human endothelin B receptors generated by alternative splicing from a single gene. AB - A novel variant of endothelin B receptor (ETB) has been found in human brain, placenta, lung, and heart by reverse transcriptase polymerase chain reaction. This variant ETB1 has an additional 30 nucleotide sequence with splice sites at both ends. This results in a 10 amino acid increase in the length of the second cytoplasmic domain of ETB. Polymerase chain reaction on genomic DNA indicates that this sequence is part of the 134 bp intron which separates the second and third exons and is contiguous with the third exon of the ETB gene. Southern blot analysis of chromosomal DNA and genomic PCR results indicate that ETB1 arises by alternative RNA splicing of the single copy ETB gene. The insert sequence in ETB1 gene is absent in bovine, rat, and porcine DNA, and is unique to human DNA. Both ETB and ETB1 have been expressed in heterologous systems to examine their ligand binding and functional properties. Reverse transcriptase polymerase chain reaction of RNA from ETB1 expressing cells indicates that the additional sequence is stably expressed. PMID- 7866431 TI - Characterization of the human MSX-1 promoter and an enhancer responsible for retinoic acid induction. AB - Previous studies have shown that the expression of some human HOX genes can be induced by retinoic acid (RA) in cultured embryonal carcinoma (EC) cells. However, the mechanisms for the regulation of HOX gene expression by RA are still unclear. We have examined the effects of RA on the human MSX-1 (formerly named HOX-7) gene expression in cultured EC cells (NT2/D1). Furthermore, we have cloned and characterized the human MSX-1 promoter and analyzed the activities of the promoter in response to RA. Our results demonstrate that transcription of human MSX-1 is activated by RA in cultured EC cells. This activation is dose and time responsive. The MSX-1 promoter was shown to be TATA-box independent and able to promote transcription in RA-treated EC cells. DNase-I footprinting studies revealed protection of several GAGA factor binding sites and an NF-kappa B site upstream to the transcription start site by nuclear extracts prepared from EC cells. A downstream sequence was differentially protected by the nuclear extract from RA treated cells. This differential binding of the sequence with the nuclear extract was further confirmed by gel shift assays. This sequence confers to a heterologous promoter with the ability to respond to RA induction. Point mutation within this DNA fragment abolished the binding of the fragment to the nuclear extract and the response of this element in a heterologous promoter to RA induction. Deletion of this enhancer element together with the adjacent NF-kappa B and GAGA sites abolished the ability of the promoter to direct transcription in RA-treated EC cells. However, removal of a downstream DNA fragment from the promoter endowed the promoter with the ability to direct transcription in RA untreated cells. Taken together, both positive and negative regulatory cis elements are involved in the regulation of the MSX-1 promoter and coordinate to control the gene expression. PMID- 7866432 TI - Farnesylation of p21 Ras proteins in Xenopus oocytes. AB - Unprocessed p21 Ras proteins microinjected into Xenopus oocytes were radiolabeled by coinjected [3H]farnesyl pyrophosphate, a direct farnesyl donor substrate for all known mammalian farnesyltransferases. Mevinolin, an inhibitor of HMG CoA reductase which reduces the levels of mevalonate and thus farnesyl pyrophosphate, blocked oncogenic H-Rasva112 induced germinal vesicle breakdown in oocytes. This mevinolin caused block was completely reversed by co-injected farnesyl pyrophosphate. The putative farnesyltransferase in Xenopus oocytes was identified to be similar to those found in mammalian cells in that it requires an intact CAAX box motif in addition to the conserved cysteine residue at the fourth position from the C-terminus of Ras proteins for its farnesylating activity. Peptide inhibitors of farnesyltransferase such as CVIM and TKCVIM were shown to inhibit farnesylation of microinjected Ras proteins thereby blocking its function namely the induction of oocyte maturation. These results demonstrate that Xenopus oocytes process bacterially produced mammalian Ras proteins in a manner similar to, if not identical with that in mammalian cells, thus validating the continued use of the Xenopus oocyte system for unraveling the functions of Ras proteins. Furthermore, our results indicate that the oocyte system may be a useful in vivo model for studying the farnesylation of human Ras proteins, its regulation, and the effects of farnesyltransferase inhibitors. PMID- 7866433 TI - Induction of anchorage independent growth and serum resistance in immortalized human bronchial epithelial cells by alteration of the cytoskeleton. AB - Malignant transformation is frequently accompanied by obvious changes in cytoarchitecture, but the importance of these changes has been difficult to assess in view of the large number of other cellular changes that also occur. In this study, we transfected the SV40-immortalized human bronchial epithelial cell line, BEAS-2B, with human wild-type beta or gamma actin gene expression plasmids to induce cytoskeletal changes and to determine whether this was associated with altered cellular growth properties. Cells expressing the exogenous full-length actin genes underwent a fibroblastoid change in morphology which was reflected in changes in their pattern of actin cable organization, and acquired both the ability to grow under anchorage-independent conditions and resistance to the normal growth inhibitory effects of fetal bovine serum. These phenotypic changes correlated with changes in actin mRNA levels, but not with changes in actin protein levels. The phenotypically altered cells were not tumorigenic when injected subcutaneously in athymic nude mice, and they retained the ability to suppress the tumorigenic potential of a lung carcinoma cell line, HuT-292. Therefore, alteration of the cytoskeleton of immortalized human bronchial epithelial cells resulted in the acquisition of some properties commonly found in malignant cells, but did not result in tumorigenicity. PMID- 7866434 TI - Hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), and their receptors in human breast cells and tissues: alternative receptors. AB - We sought to determine whether the hepatocyte growth factor/scatter factor (HGF/SF)- and keratinocyte growth factor-receptor systems were expressed in normal breast cells, breast carcinoma cell lines, normal breast tissues, and breast cancer tissues. Reverse transcriptase-polymerase chain reaction and hot blotting were used to detect HGF, HGF/SF (met) receptor, KGF, and KGF receptor mRNAs in human mammary epithelial (HME) and stromal (HMS) cells. We also examined breast carcinoma (MDA-MB-157, SCC 38, and SCC 70) and spontaneously immortalized breast epithelial (HMT 3522) cell lines, as well as normal breast and breast carcinoma tissues. PCR products were also confirmed by nucleic acid sequencing. The effects of HGF and KGF, compared to EGF and heparin-binding EGF, on the proliferation of normal human mammary epithelial cells in serum-free defined medium was determined by cell counting. HGF and KGF mRNAs were detected in HMS cells, but not HME cells. KGF receptor mRNA was detected in HME cells, but not HMS cells. HGF/SF receptor mRNA was detected in both HME and HMS cells. mRNAs were also detected in normal breast and breast carcinoma tissues, as well as breast carcinoma and transformed breast epithelial cell lines. Alternative cDNA sequences that are predicted to code for a soluble KGF receptor and a membrane bound, truncated HGF/SF receptor were detected in breast epithelial cells and breast tissues. HGF and KGF maintained viability and stimulated proliferation of HME cells. PMID- 7866436 TI - Bibliography of cellular and molecular biology research. PMID- 7866435 TI - Existence of multiple phosphorylated forms of human platelet actin binding protein. AB - Platelet actin binding protein (ABP) as isolated from human platelets exists in at least four phosphorylated forms which we have designated ABP-0, ABP-1, ABP-2, and ABP-3 whose phosphate content ranges from 18 (ABP-0) to 40 (ABP-3) moles Pi/mole ABP. These forms differ in their resistance to calpain cleavage and ability to cross-link F-actin with ABP-3 being the best in each of these properties. Attempts to phosphorylate ABP-1, two or three with protein kinase C (PKC) were unsuccessful except if the proteins were pretreated with Escherichia coli alkaline phosphatase. All of the forms could be phosphorylated with cAMP dependent kinase (PKA) and subsequent resistance to calpain cleavage conferred. Phosphorylation/dephosphorylation of ABP may be an important regulatory mechanism by which the cytoskeletal architecture is stabilized or transformed. PMID- 7866437 TI - Southern California's newest wave: an association for integrators. PMID- 7866438 TI - A new rhythm for the Blues. AB - If 1994 was the year the nation's Blue Cross and Blue Shield plans surpassed their managed care competitors in enrollment, 1995 is shaping up to be the year the Blues lead the stampede to form integrated delivery systems. Plus, a look at the new BC/BS chief, Patrick Hays. PMID- 7866439 TI - The Vista Awards. New facilities for a new age. AB - To build an outstanding health care facility, you need to start with an outstanding project team. That's the premise underlying the first Vista Awards. A look at the winning projects and teams. PMID- 7866440 TI - Is there a cure for Medicare's outpatient payment pains? AB - Though HCFA is getting ready to release a new report to Congress on Medicare outpatient payment reform, there's consensus that a broad overhaul of the outpatient payment system is still in the distance. So when--and how--will the nightmare of a broken payment system be fixed? PMID- 7866441 TI - Healthier times at Ridgemont High. AB - In a growing number of communities around the nation, school-based health clinics are providing a place where kids and teens can turn for everything from an annual physical examination to confidential alcohol and substance abuse counseling to teen parenting classes. PMID- 7866442 TI - Information systems. Retro tech. PMID- 7866443 TI - Prepaid pitfalls. Don't lose your head. PMID- 7866444 TI - Alan B. Miller, Chairman and CEO, Universal Health Services. Interview by Kevin Lumsdon. PMID- 7866446 TI - Mergers. 180 seamless sites. PMID- 7866445 TI - Self-referral ban. Clear as mud. PMID- 7866447 TI - How markets evolve. PMID- 7866448 TI - Baby pictures. Rural health network turns 1. PMID- 7866449 TI - Serious fun. Zap! Zowie! Pow! PMID- 7866450 TI - HospitalPulse. Autumn leaves. PMID- 7866451 TI - Witness to the revolution. PMID- 7866452 TI - Docs' biggest deficit: people skills. PMID- 7866453 TI - Suicide. State-by-state look at a national tragedy. PMID- 7866454 TI - [The width-length quotient of the glottis as a measure of amplitude values]. AB - The vibratory width of the glottis plays an important role in the diagnosis of functional voice disorders. The experienced examiner decides if the amplitudes of the vocal folds are normal, too small or too wide, always with regard to the length of the glottis. Therefore the width-length quotient is an adequate measurement for the vibratory width of the glottis. To standardize this quotient, we made stroboscopic measurements in 82 normal-voiced persons; 41 were female, 41 male. The pitch was in the range of the speaking voice at medium loudness. Statistical evaluation was done by box-and whisker plots. The width-length quotient of the glottis shows a minimum of 0.1 in both sexes with a maximum of 0.31 in men and 0.26 in women. The average was 0.16 in men and 0.17 in women. 50% of the width-length quotient near the median are inside the box, ranging from 0.14 to 0.2. Results on the lower part of the scale point towards a hyperfunctional voice disorder (small amplitude), while results in the upper part (0.2 and more) show a tendency towards hypofunction with comparatively wide amplitudes. PMID- 7866455 TI - Priority as frequency. AB - The centerpiece of determinacy grammar (DG) is determinacy form (DF). According to DF, a binder (z) binds an argument (x) to a predicate (y) with certain amounts of accuracy (I) and completeness (C), where I and C are defined in terms of frequencies (N): I = N(xy)/N(x) and C = N(xy)/N(y). DF is written: x,z-->y, I = m and C = n, where the values of I and C fall between 0.00 and 1.00. In this paper it is argued that priority = frequency. By this we mean that the spatial relations 'before--after' and the temporal relations 'earlier--later' are best understood as the frequentative relations 'less frequent--more frequent'. The Aristotelian interpretations of 'priority' are reexamined in this frequentative light, and it is concluded that relations of space and time are available to DG as relations of frequency. The leads to the question of frequency in DG, consisting of (1) a data matrix (DM) and (2) a determinacy analysis (DA) whose movements orchestrate DF. A typology of DM movements is given, and it is shown that 'earlier' and 'later' movements involve lower and higher frequencies, respectively. Moreover, it is found that DF qua movement suggests the existence of several movement-related frequency types. PMID- 7866456 TI - Determinacy experience. AB - In this article we concisely describe our theoretical framework, determinacy grammar (DG), including accounts of the determinacy data matrix (DM) and determinancy analysis (DA), together with the associated notions of determinacy accuracy (I) and determinacy completeness (C). The topic of the article is determinacy experience (DE), which we bifurcate into (1) the determinacy of experience [D(E)] and (2) the experience of determinacy [E(D)]. Crucially, the relations involved are held to be frequentative rather than either temporal or spatial. Moreover, there is a need for a priori knowledge in the DM, namely, knowledge of determinacy form (DF), in particular, form which is frequentative rather than temporal or spatial. Finally, questions of knowledge acquisition, attrition (whether in normalcy or pathology), and variation are discussed. We conclude with a conspectus of the contents and some suggestions for further research. PMID- 7866457 TI - [Laryngeal contact granuloma--a psychosomatic disorder?]. AB - In a multidimensional design using the hypothesis of a psychosomatic genesis, 28 patients (1 female, 27 male) showed, in their personality profile, increased scores in 'impulsiveness', 'emotionality (neuroticism)', 'strain' and 'inhibition'. In addition to the voice disorders other somatic symptoms were observed, especially general symptoms as dysthymia, depression and excessive vegetative stimulation. Their social competence was reduced by the fear of making contacts and the inability 'to say no'. Also psychosocial stress factors were registered due to loss of a loved one with feelings of an existential danger. Thus, contact granuloma can be considered as a secondary reaction to a specific combination of personal disposition and social life situation. Lastly a causal model is presented, which can be used as a diagnostic criterion. PMID- 7866458 TI - [Stuttering in childhood: etiology and follow-up. Initial results of a 5-year longitudinal study]. AB - For about 15 months a multifactorial longitudinal study on the development of stuttering in preschool children has been conducted at the Phoniatric Outpatient Department of the University of Ulm. The main subject of the study is to determine valid indicators to estimate the risk of future chronicity or remission of stuttering and to find out whether and how it is possible to differentiate normal developmental dysfluencies from chronic abnormal dysfluencies. Preliminary results are presented and discussed. PMID- 7866459 TI - Biobehavioral effects of weight cycling. AB - An association between weight cycling and mortality and morbidity has been pointed out in epidemiological studies. However, the mechanisms underlying this association are difficult to demonstrate, and earlier studies have been contradictory. In this work we investigated several mechanisms which have been suggested as possible mediators for the association between weight cycling and a number of prevalent diseases. Fat consumption, fat preference, fat distribution and metabolism, lipid profile, oral glucose tolerance test (OGTT), blood pressure and steroid hormone determinations were performed in 28 women with or without a weight cycling history, who were matched for weight and age. No differences were found between cyclers and non-cyclers for any of the behavioral, physiological, metabolical and health parameters measured, with the exception of an increase in subcutaneous abdominal fat in the cyclers. It was concluded that, in generally healthy young women, weight cycling does not differentially increase risk factors that are harmful for health. However adverse effects might still be detectable in situations where women are biologically challenged. PMID- 7866461 TI - Overweight and obesity in Italy, 1990-91. AB - Overweight and obesity are associated with several important diseases, including diabetes, cardio- and cerebrovascular diseases, digestive disorders and cancer. We decided, therefore, to present estimates of the prevalence of overweight and obesity in the general Italian population. The prevalence of overweight and obesity in Italy was evaluated using data from the 1990-91 Italian National Health Survey. 25,818 households were surveyed, representing the whole Italian population. A sample of 24,602 males and 26,090 females aged 15 or over was randomly selected, within strata of geographical area, size of municipality and size of household, in order to be fully representative. Quetelet's index was considered as a measure of body mass index, on the basis of self reported height and weight, and was a priori divided into four levels: underweight (< 20 kgm-2), normal weight (20 to 24.9 kgm-2), overweight (25 to 29.9 kgm-2), and obese (> or = 30 kgm-2). In the overall national sample, 11.0% of subjects were underweight (4.4% males, 12.2% females), 50.8% normal weight (49.4% males, 52.2% females), 31.6% overweight (39.2% males, 24.5% females), and 6.5% obese (7.0% males, 6.1% females). The prevalence of overweight and obesity was higher in middle age and in the South of the country, and was directly related to history of diabetes, hypertension, heart diseases, gallbladder disease and chronic respiratory disorders. These data quantify the importance of overweight and obesity as a public health issue in the general Italian population. PMID- 7866460 TI - The free testosterone to dehydroepiandrosterone sulphate molar ratio as a marker of visceral fat accumulation in premenopausal obese women. AB - The aim of this paper was to investigate the relationship between sex hormones and fat distribution in premenopausal obese women. Serum concentrations of sex hormones, glucose tolerance and fat distribution were determined in a population of non-diabetic obese women, in the outpatient clinic of University Hospital, Bari, Italy. The subjects were 40 consecutive premenopausal obese women (BMI > 25). The amounts of visceral, abdominal subcutaneous, and femoral subcutaneous fat, and the visceral to abdominal subcutaneous fat ratio were measured by ultrasound techniques. Serum concentrations of total testosterone (T), free testosterone (FT), dehydroepiandrosterone sulphate (DHEAS), delta 4 androstenedione (A), 17-beta-estradiol (E2), sex hormone binding globulin (SHBG), and the FT to DHEAS molar ratio were measured during the follicular phase. Plasma glucose and insulin concentrations were evaluated during an oral glucose tolerance test. Of all sex hormones, the FT/DHEAS molar ratio was the parameter that most closely related to the amount of visceral fat (r: 0.544, P < 0.001), and this positive association was maintained (P < 0.01) after adjustment for age, BMI and insulin levels (fitted model: R2 adjusted: 0.504; F ratio: 14.73; P value: < 0.0001). DHEAS was inversely correlated with the amount of visceral fat (r: -0.324, P < 0.05). T was inversely correlated with the amounts of both abdominal subcutaneous (r: -0.409, P < 0.01) and visceral fat (r: -0.324, P < 0.05). The FT to DHEAS molar ratio is the androgenic parameter that most closely relates to the accumulation of visceral fat in premenopausal obese women. PMID- 7866462 TI - Size, fatness and relative fat distribution of males of contrasting maturity status during adolescence and as adults. AB - The somatic characteristics of boys of contrasting biological maturity status during adolescence are compared from 13-18 years and at 30 years of age. Within the mixed longitudinal Leuven Growth Study of Belgian Boys, 173 boys were followed annually from 13-18 years and were subsequently measured at 30 years of age. Age at peak height velocity (PHV) was estimated for 149 boys and the sample was then divided into three contrasting maturity categories based on the age at PHV: early (PHV < 13.37 years), average (PHV between 13.85 and 14.80 years) and late (PHV > 15.27 years) maturers. Using ANOVA for repeated measures and one-way ANOVA, differences in 18 somatic dimensions and five ratios of body proportions and subcutaneous fat distribution among the three maturity groups were tested from 13-18 years and at 30 years of age. There are consistent differences among boys of contrasting breadths, circumferences,and skinfolds on the trunk. There are no differences in skinfolds on the extremities. None of the differences in somatic dimensions and ratios among the three contrasting maturity groups are significant at 30 years of age except those for subscapular skinfold and the trunk/extremity skinfold ratio. Thus, during adolescence and in adulthood, late maturing boys have a distribution of subcutaneous fat that is associated with lower risk for several adult degenerative diseases. PMID- 7866463 TI - Chronic fenfluramine treatment: effects on body weight, food intake and energy expenditure. AB - Fenfluramine suppressess the body weight of experimental animals during chronic treatment by a mechanism that is not yet clear. The present research investigated the contributions of fenfluramine-induced alterations in food intake and two components of energy expenditure, resting energy expenditure (REE) and the thermic effect of food (TEF), to maintenance of a lowered body weight in male Long Evans rats. DI-Fenfluramine (20 mg/kg) produced an initial severe anorexia and weight loss. Food intake then increased steadily, reaching control levels by the fourth day of treatment. Tolerance to the anorectic effects of fenfluramine was not complete however -- food intake of fenfluramine-treated rats fell below control levels on 7 of the remaining 20 days of treatment. The body weight of fenfluramine treated rats remained significantly below control levels throughout the entire treatment period, but rose rapidly to control levels following fenfluramine withdrawal. REE was unaffected by fenfluramine treatment. By contrast, fenfluramine treatment significantly altered the TEF. Twenty-four hours after initiation of treatment the TEF of fenfluramine treated animals was higher than that of controls. On the 15th day of drug administration and the first day of fenfluramine withdrawal, however, the TEF of control and treated animals no longer differed. By contrast, on the second day of fenfluramine withdrawal the TEF of fenfluramine treated rats was suppressed to 17% of control levels. These findings suggest that the effect of fenfluramine on body weight involves modulation of both food intake and energy expenditure. PMID- 7866464 TI - Abdominal obesity and mortality risk among men in nineteenth-century North America. AB - The health consequences of an adverse body-fat distribution (e.g., android, upper body, visceral) have only recently concerned the medical community. Ninety years ago, however, actuarial study demonstrated the relationship of body-fat distribution to the mortality experience of insured, North American men. Thirty four insurance companies pooled their data on males issued life policies between 1870 and 1899. Special classes of risk were defined by weight for height at baseline or by the observation that abdominal girth exceeded the girth of the expanded chest (abdominal obesity). The mortality experience of each risk class was compared to an age-stratified, actuarial table of the period. We present new analyses of these historical data relating specifically to the mortality impact of abdominal obesity. Among 163,567 overweight men, the prevalence of abdominal obesity increased with age and with degree of overweight. Among moderately overweight men, those with abdominal obesity experienced 133% of the expected mortality rate compared to 112% of the expected mortality for those who were not abdominally obese. Severely overweight men with abdominal obesity experienced 152% of the expected mortality compared to 135% of the expected mortality for severely overweight men who were not abdominally obese. We believe this nineteenth-century, acturial study of waist and chest girths was the first demonstration that body-fat distribution can influence longevity. These early actuarial findings, taken with more recent reports, establish that abdominal enlargement, but not necessarily an 'upper-body' fat distribution, constitutes a major health hazard. Future research must establish which abdominal-obesity index best predicts disease outcomes. PMID- 7866465 TI - Six months' follow-up on exercise added to a short-term diet in overweight postmenopausal women--effects on body composition, resting metabolic rate, cardiovascular risk factors and bone. AB - The aim of this work was to study the long-term effects of the addition of exercise to a short-term diet in overweight postmenopausal women. A follow up study was made of 118 overweight, postmenopausal women, who 6 months earlier had completed 12 weeks of randomized intervention (three groups: 4.2 MJ/d diet, 4.2 MJ/d diet with exercise, and controls). The following were measured: body composition and fat distribution (measured by dual-energy X-ray absorptiometry), resting metabolic rate, serum lipids and lipoproteins, blood pressure, and bone mineral densities. It was found that weight was still significantly reduced (by about 8 kg). HDL-C was significantly increased (10%), and triglycerides decreased (20%), whereas the initial reductions in total cholesterol and LDL-C had disappeared at the follow-up. The women from the former diet-plus-exercise group, who were current exercisers at the follow-up, had a significantly greater reduction in weight (10.9 vs 6.6 kg), fat tissue mass (10.0 vs 5.4 kg) and abdominal-to-total-body fat tissue mass (9.6 vs 4.7), and a significantly greater increase in the resting metabolic rate (11.1 vs 1.1 kJ/kg/d), as compared with the non-exercisers from this group. There were no major detrimental changes in total body, spinal, or forearm bone mineral density or in markers of bone turnover. The short-term dietary treatment in this study may have beneficial long term effects on weight, fat tissue mass and cardiovascular risk factors with no additional benefits from added exercise, unless the exercise is continued. PMID- 7866466 TI - Association between reduced lymphocyte beta-adrenergic receptors and left ventricular dysfunction in young obese subjects. AB - This study was designed to evaluate total (t) and surface (s) beta-adrenergic receptors (BAR) density and their relationships with left ventricular function in young obese subjects. BAR density, plasma insulin, catecholamines and left ventricular function were evaluated in 27 young obese subjects (BMI > 30.5 kg/m2 for males and > 27.3 kg/m2 for females) without other risk factors for cardiovascular diseases (smoking, hypertension, diabetes and lipid abnormalities) and in 20 lean controls (BMI < 25 kg/m2 for males and < 24.7 kg/m2 for females). Both groups were matched for gender, age and body height. BAR density was evaluated according to Boyum and De Blasi methods. Plasma catecholamines by high perfusion liquid chromatography and fasting immunoreactive plasma insulin (IRI) levels by RIA were also measured. Casual (c) and 24 h ambulatory mean blood pressure (MBP/24h) were determined. Radionuclide angiocardiography was used to measure left ventricular ejection fraction (LVEF), peak filling rate (PFR), time to PFR (tPFR), cardiac output (CO) and stroke volume (SV). Total left ventricular mass (LVM), indexed for height (LVM/H), left ventricular diastolic dimension (LVDD) and interventricular septal (IVS) thickness by echocardio-graphic study were calculated. LVEF, PFR, BARt, BARs were significantly lower (P < 0.0001) and plasma IRI, CO, SV (P < 0.0001), LVM (P < 0.003), LVM/H (P < 0.004), LVDD (P < 0.02) and tPFR (P < 0.02) were significantly higher in obese subjects than in lean controls. BARt and BARs correlated inversely with BMI, SV and LVDD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866467 TI - Physicians' diagnosis of obesity status in NHANES II. AB - The aim of this work was to assess the accuracy of physicians' subjective assessments of obesity status. The subjects were participants in The Second National Health and Nutrition Examination (NHANES II) Survey. The physicians' subjective judgments of obesity were compared to BMI, an objective measure of actual body mass. Subjects with a body mass index (BMI = weight in kg/(height in cm/100)2) less than or equal to 27.5 were classified as normal weight and those with a BMI greater than or equal to 30.4 were considered to be obese. Physicians were accurate in their diagnosis of the normal weight group with only 4.03% being misdiagnosed as obese. However, 12.6% of the obese group was misdiagnosed as normal weight. The odds of an incorrect normal weight diagnosis increased with age. Similarly, as the fat distribution ratio increased, i.e., a more central pattern, the odds of being actually obese but incorrectly diagnosed as normal weight increased. Men were more likely than women to be incorrectly diagnosed as normal weight. Non-Caucasian normal weight persons appear to have been diagnosed more stringently than Caucasians as they were more likely to be misdiagnosed as obese regardless of their gender. There appear to be several variables affecting the physicians' subjective assessment of obesity status in this data set. PMID- 7866468 TI - Prevalence of obesity among patients admitted for elective orthopaedic surgery. AB - The aim of this work was to test the hypothesis that obesity is more common among patients requiring elective orthopaedic surgery than in the general population. A cross-sectional survey was carried out on 2673 consecutive patients admitted from the waiting list for four common types of operation: removal of lumbar intevertebral disc herniation, total hip replacement, elective knee arthroscopy or total knee replacement. Patients with primarily inflammatory joint disease were excluded. The immediate preoperative relative body weight, calculated as body mass index (BMI), of the patients was compared with data available on a general population sample of 44,034 people. Obesity was defined as BMI greater than the BMI + one standard deviation of the corresponding age and sex category of the general population. By these criteria, 256 patients (27%) with lumbar intervertebral disc herniation, 192 (24%) with total hip replacement, 135 (22%) with knee arthroscopy and 80 (27%) with knee replacement were obese, whereas the proportion in the general population was 16%. A major difference with the general population emerged in young patients of both sexes operated on for lumbar disc herniation and in women admitted for knee arthroscopy. The mean BMI of men aged 20 to 49 years subjected to knee arthroscopy did not differ from the general population. It was concluded that overweight people seem to be strongly over represented among the patients requiring common orthopaedic surgical procedures. PMID- 7866469 TI - Exercise and FFM during diet-induced weight loss. PMID- 7866470 TI - A comparison of the thermogenic, metabolic and haemodynamic responses to infused adrenaline in lean and obese subjects. AB - The objective of this work was to study adrenoceptor sensitivity in vivo in a number of tissues in lean and obese humans. The thermogenic, metabolic and cardiovascular responses to a 90 min infusion of adrenaline were measured. The subjects were eleven obese subjects (Body Mass Index 36.0 +/- 1.2 kg/m2) and 10 non-obese subjects (Body Mass Index 21.9 +/- 0.7 kg/m2). Metabolic rate, heart rate, blood pressure, forearm blood flow, plasma palmitate turnover and oxidation were measured. Thermogenic responses to adrenaline were similar in the lean and obese groups (14.4 +/- 1.6 and 15.1 +/- 1.6 J/min/kg fat free mass respectively). Of the cardiovascular variables measured, only the increase in forearm blood flow during adrenaline infusion differed between lean and obese, being 3.9 +/- 0.5 and 1.9 +/- 0.3 ml/min/100 ml forearm respectively. Basal plasma palmitate turnover rates were lower in the obese when expressed per unit fat mass (2.32 +/- 0.17 and 7.61 +/- 1.20 mumol/min/kg fat mass respectively). Basal plasma palmitate oxidation rates were higher in the obese when expressed per unit fat free mass (1.53 +/- 0.19 and 0.82 +/- 0.12 mumol/min/kg fat free mass respectively). In response to adrenaline palmitate turnover increased similarly in both groups, but plasma palmitate oxidation rates fell in the obese whilst they were unchanged in the lean. In the basal state the obese do not appear to have a defect in fat oxidation, but their response to infused adrenaline may favour fat storage over oxidation. No thermogenic defect was shown in the obese. PMID- 7866472 TI - Waist-to-hip ratio and judgment of attractiveness and healthiness of female figures by male and female physicians. AB - Sexual dimorphism in body fat distribution as measured by waist-to-hip ratio (WHR) is unique to humans. The WHR has been shown to be an accurate predictor of risk for various diseases, premature mortality, degree of androgenicity/estrogenicity and fecundity of women, independent of overall body weight. This study investigated whether physicians would be influenced by body size or WHR in assessing health, youthfulness, and reproductive capability of a woman. Line drawings of 12 female figures representing three categories of body weight (normal, underweight and overweight) and four sizes of WHR (0.7, 0.8, 0.9 and 1.0) were ranked by male and female physicians for these qualities as well as for attractiveness and intelligence. Both males and females assigned higher ranking for many of these qualities to normal weight figures with low WHRs (0.7 and 0.8). Overweight figures were assigned low rankings for all these qualities except reproductive capability. Underweight figures, regardless of WHR size, were assigned low ranking for reproductive capability and those underweight figures that had high WHRs (0.9 and 1.0) were assigned low ranking for healthiness. While there were minor sex differences in ranking of some attributes for some figures, generally both male and female physicians utilized the WHR in a similar manner to infer healthiness, reproductive capability and attractiveness. PMID- 7866471 TI - The effects of weight loss in obese subjects on the thermogenic, metabolic and haemodynamic responses to the glucose clamp. AB - The aim of this work was to examine the effects of weight loss in obese subjects on the thermogenic, metabolic and cardiovascular responses to a glucose clamp. Resting measurements were made, followed by a hyperinsulinaemic (100 mU/m2/min) euglycaemic clamp (4.5 mmol/l). The subjects were six healthy, obese subjects (mean body mass index before weight loss 37.0 +/- 1.7 kg/m2 and after weight loss 31.4 +/- 2.3 kg/m2). The following measurements were made: indirect calorimetry, blood pressure, heart rate, forearm blood flow, plasma catecholamines, plasma deuterated glucose turnover before and during a glucose clamp. Glucose disposal during the clamp increased from 2.53 +/- 0.40 to 3.31 +/- 0.42 mmol/min after weight loss (P < 0.01). Glucose-induced thermogenesis rose from 0.15 +/- 0.09 to 0.50 +/- 0.12 kJ/min (P < 0.05). The apparent cost of glucose storage was not significantly different from zero prior to weight loss, but increased to 11.0 +/- 2.2% after weight loss. In response to the clamp endogenous glucose production was suppressed by 66 +/- 7% initially and this was not affected by weight loss. Weight loss was accompanied by increased peripheral insulin sensitivity and glucose-induced thermogenesis, but it did not affect hepatic insulin sensitivity. PMID- 7866473 TI - The effects of loxiglumide on food intake in normal weight volunteers. AB - The aim of this paper was to investigate the effects of the CCK, a receptor antagonist loxiglumide on food intake, hunger and fullness in humans. A double blind, placebo controlled, cross-over test was carried out, with subjects taking one loxiglumide or one placebo tablet three times a day, 15 min before main meals or at comparable intervals. The work was carried out at the Centre for Human Nutrition, Northern General Hospital, University of Sheffield, on 11 healthy, normal weight, male and female volunteers. The following were measured: weighted intake measurement of food intake during drug and placebo treatment; laboratory test of food intake on day three of each treatment; hunger and fullness ratings throughout this meal. A small, non-significant, increase in food intake as measured by the weighed intake diaries (8577 +/- 636 vs 7895 +/- 569 kJ (2049 +/- 152 vs 1886 +/- 136 kcal); P = 0.17) was seen during loxiglumide treatment, but no effect on food consumption from the evening test meal was observed and no effect on feelings of hunger and fullness before or after this meal was seen. These results do not support the hypothesis that, in the free feeding situation, endogenously released CCK is involved in the reduction of food intake or inhibition of hunger. However, a different dose of route of administration or a larger group of subjects may reveal an effect of loxiglumide on feeding in humans. PMID- 7866474 TI - Evaluating success of weight loss programs, with an application to fluoxetine weight reduction clinical trial data. AB - We modified criteria for judging successful obesity treatment proposed by Atkinson to provide objective criteria for successful benefit from weight reduction programs with respect to data from a clinical trial. The criteria include assessments of changes in both weight-related factors (e.g. excess weight, excess body fat) and obesity-related risk factors (e.g. hypertension, hyperglycemia, hyperlipemia). To demonstrate the use of this methodology, we applied the criteria in an analysis of eight randomized, double-blind controlled trials comparing fluoxetine (n = 522) with placebo (n = 504) for weight loss. The results suggest these criteria can be useful for evaluating a treatment program or for comparing treatments from clinical trials. PMID- 7866475 TI - Body mass index and mortality in Seventh-day Adventist men. A critique and re analysis. AB - The aim of this work was to determine if the relationship between weight-adjusted for-height (expressed as body mass index or BMI) using the BMI-at-entry and age at-entry as opposed to BMI at entry and age-at-event (i.e. death, loss to follow up, or end of the study) would alter the results previously reported from a population of Seventh-day Adventist men. The subjects were 8828 non-smoking, non drinking Seventh-day Adventist men, ages 30-89 and older on entry, mean follow-up 15 years (maximum 26 years). The BMI and age reported by subjects when they were enrolled into the study were used to calculate the relationship between BMI and mortality. Mortality rates in each of five BMI quintiles were computed by dividing the number of deaths in each quintile by the number of person years of follow-up in the quintile. Rate ratios were computed by dividing each mortality rate by the rate in the reference quintile. The mortality rate ratios were then adjusted for the age difference between each quintile and the reference quintile. Calculations based upon age-at-enrollment rather than 'age-at-event' (as used in the original paper) demonstrate no increase in mortality until a BMI of 27.5 kg/m2 or greater is reached rather than a progressive increase in mortality with increasing BMI. PMID- 7866476 TI - Relationship between insulin sensitivity and circulating sex hormone-binding globulin levels in hyperandrogenic obese women. AB - The aim of this work was to examine the effect of an insulin infusion on SHBG levels as well as the relationship between SHBG levels and insulin sensitivity. Acute insulin infusion was used with the insulin-glucose clamp technique. The subjects were 14 consecutive well-characterized hyperandrogenic non-diabetic obese women without biological and echographic symptoms of polycystic ovary syndrome. Adiposity and fat distribution were assessed respectively by the body mass index (BMI: 38.7 +/- 1.6 kg/m2) and by the waist hip ratio (WHR: 0.91 +/- 0.01). Hyperandrogenism was evidenced by hirsutism and serum testosterone greater than 2.8 nM. Circulating SHBG levels were determined in the fasting state by RIA. Insulin sensitivity was assessed using the euglycemic hyperinsulinemic glucose clamp technique with three incremental doses of insulin. Seven non-obese non hyperandrogenic subjects (BMI: 21.0 +/- 0.6 kg/m2) served as controls for the study of the insulin resistance state. Because of supraphysiological insulin infusion rates (40, 100, and 350 mU/min.m2, each dose for 2 h), insulin sensitivity was mainly studied at peripheral level. We calculated the Km, i.e. the ED50 of the dose-response curve, the glucose disposal rate, and the maximal glucose disposal rate per U insulin (M/I). The hyperandrogenic obese subjects exhibited marked insulin resistance. SHBG levels, although already in the lower half of normal in the basal state, decreased from 34.8 +/- 3.4 nmol/l to 29.7 +/- 3.3 nmol/l (P = 0.001; normal values are 18-83 nmol/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866477 TI - Early decrease in GLUT4 protein levels in brown adipose tissue of New Zealand obese mice. AB - The aim of this study was to determine if the previously described insulin resistance in the New Zealand Obese (NZO) mouse is associated with a decrease in GLUT4 protein and if such changes occur early in the evolution of the syndrome. GLUT4 levels were measured in whole membranes isolated from a variety of tissues in 4 and 20-week-old NZO and control NZC mice by Western blotting using a specific antibody to the C terminal end of the protein. At 20 weeks of age, GLUT4 levels were lower in the NZO mice in brown and white adipose tissue, heart, diaphragm, red and white quadriceps, and red and white gastrocnemius, but not in soleus muscle. At 4 weeks of age, GLUT4 levels were 52% lower in BAT (3309 +/- 1006 vs 6951 +/- 1870 cpm P = 0.039) but were not lower in WAT, heart or red quadriceps. It is concluded that adult NZO mice have a decrease in GLUT4 levels in most insulin-sensitive tissues and that in BAT, this occurs at an early age. PMID- 7866478 TI - Glycemic response to stress is altered in euglycemic Pima Indians. AB - The aim of this work was to study the effects of a computer-driven mental arithmetic task on blood glucose in a group of four male and four female euglycemic Caucasians and a group of seven male and six female euglycemic Pima Indians. Approximately 60% of euglycemic Pima Indian Native Americans eventually develop type 2 diabetes, while only 5% of Caucasians develop the disease. All subjects had normal glucose tolerance. Subjects were given a standard breakfast; 2 h later, they were given a computerized mental arithmetic stress test for 10 min. Before, during and after the test, several variables were analyzed, including serum concentrations of glucose, insulin, glucagon and plasma cortisol and catecholamines. Heart rate, systolic and diastolic blood pressure and all the stress hormones increased during stress and decreased during recovery in all subjects. Blood glucose consistently declined one hour after the meal in all subjects. However, while it continued to decline following stress in seven out of eight Caucasian subjects, it consistently increased during and following stress in 10 out of 13 Pima Indians. Fasting serum glucose in Pima Indians and Caucasians was respectively 5.07 + 0.08 mM and 5.04 + 0.09 mM. Two-hour post prandial values were 5.63 + 0.22 mM and 5.48 + 0.19 mM respectively, whereas post stress values were 6.15 + 0.19 mM for Pima Indians and 5.22 + 0.20 mM for Caucasians. Both serum glucose means following stress (t = 3.1, P < 0.005) and the direction of change in serum glucose in response to mental arithmetic (chi 2 = 8.2, P < 0.01) clearly differentiated Pimas from Caucasians.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866479 TI - Anthropometric or ultrasonic measurements in assessment of visceral fat? A comparative study. AB - The main aim of the study (study 1) was to compare the accuracy of anthropometric and ultrasonic measurements in assessing the amount of visceral adipose tissue. An additional aim (study 2) was to verify ultrasound technique precision. Study 1: using computed tomography (CT) L4-L5 adipose tissue area as a gold standard we compared the accuracy of waist/hip circumference ratio, sagittal diameter and ultrasonic measurements of intra-abdominal depth in assessing the amount of visceral adipose tissue. Study 2: ultrasonic measurements of the intra-abdominal muscle-vertebra distance were made in triplicate by three different operators. In study 1, 24 volunteers were used; body mass index (BMI): 19-43. In study 2, 22 volunteers were used; BMI 20-42. In study 1, ultrasonic measurements of the abdominal depth correlated best with CT visceral adipose tissue area (r = 0.89 - 0.91). In study 2, inter-operator and intra-operator mean variation coefficients were about 7% and 5% respectively. We concluded that using a well standardized technique and properly trained operators, ultrasonic measurement of intra abdominal depth is a valid method in assessing the amount of visceral adipose tissue. PMID- 7866480 TI - Mechanism of anti-obesity action of benidipine hydrochloride in mice. AB - Benidipine hydrochloride, a dihydropyridine calcium antagonist, decreases body weight and also has a hypotensive effect. The mechanism of its inhibitory effect on body weight is unclear, although this agent increases blood flow in brown adipose tissue, which functions as a main thermogenic organ. The hypothesis that benidipine hydrochloride activates brown adipose tissue to induce body weight loss was tested on mice made obese by pretreatment with monosodium-L-glutamate (MSG). When benidipine hydrochloride was incorporated in the diet (1.0 mg per gram of food) for 4 weeks, binding of guanosine-5'-diphosphate in brown adipose tissue mitochondria was significantly increased. Body weight and body fat decreased in both MSG obese mice and in lean controls. Results support the hypothesis and suggest the possibility that benidipine hydrochloride may be useful for treating obese hypertensive patients. PMID- 7866481 TI - Failure to find behavioural differences between lean and obese Zucker rats exposed to novel environments. AB - Past studies have evidenced a key role for hypercorticism in the obesity syndrome of the Zucker (fa/fa) rat. Here, the hypothesis that obesity-related hypercorticism is associated with increased anxiety/emotionality was tested in the elevated plus-maze, the black/white box, and the open field. In the elevated plus-maze, none of the parameters examined (open arm entries, time in open arms, total number of entries) differed between lean (Fa/?) and obese (fa/fa) rats. In addition, neither the behaviours measured in the black/white box (latency to enter the black compartment, number of transitions, time spent in the white compartment, locomotion, rearing) nor those measured in the open field (locomotion, rearing, grooming, defecation) were affected by obesity. This study suggests that obesity-related hypercorticism in fa/fa rats is not associated with indices of emotionality and anxiety, at least those analysed by means of the tests used here. PMID- 7866482 TI - Tacrine treatment modifies cerebrospinal fluid neuropeptide levels in Alzheimer's disease. AB - Biochemical and histochemical studies have demonstrated a widespread deficit in the activity of acetylcholinesterase (AChE) in the brains of patients with Alzheimer's disease (DAT). Multiple disturbances in several transmitter systems have been found. The most consistent neurochemical changes in DAT are reductions in the cholinergic system. The major pharmacological approach today in DAT is based on the cholinergic theory assuming that acetylcholine has a major cortical impact on cognitive processes. Tetrahydroaminoacridine (THA, tacrine) is a centrally active reversible acetylcholinesterase inhibitor. A large number of trials have been performed in patients with DAT. This article was to evaluate whether THA treatment induced neuropeptide alteration in DAT before and after 1 year on oral THA treatment. PMID- 7866483 TI - A study of regional cerebral blood flow using 99mTc-HMPAO-SPECT in elderly women with senile dementia of Alzheimer's type. AB - Thirteen women with senile dementia of Alzheimer's type (SDAT) according to NINCDS-ADRDA and 21 age-matched control women, aged 75-96 years, were investigated with clinical examination, dementia rating scales and single photon emission computed tomography (SPECT) using 99mTc-hexamethylpropyleneamine oxime (HM-PAO) as a tracer of regional cortical blood flow. The aim was to study whether typical SPECT findings of SDAT were seen also in the very old having the disease for a longer period. Neuropsychological assessment with vocabulary and spatial tests was performed in the control women, and the results were divided in three subgroups, normal, borderline and abnormal. Regional perfusion values, expressed as a ratio between cortical and cerebellar HM-PAO uptake, were lower in frontal, temporoparietal and occipital cortices in SDAT patients than in controls. The SDAT patients had the lowest uptake in the posterior temporoparietal region (0.67 +/- 0.06) and the corresponding value in the controls (0.79 +/- 0.05) differed significantly, p < 0.0001. The interhemispheric ratio between right and left posterior temporoparietal regions was 0.99 +/- 0.05. Nine of the control women (43%) had pathological SPECT with hemispheric asymmetries in 6 cases and bilateral temporooccipital reductions in 3 women. The neuropsychological assessment matched the findings in 7 of these women. One of the control women was judged as pathological and 10 women as borderline according to the spatial and vocabulary tests. Four of the 10 women with borderline results had normal SPECT. The sensitivity of the assessment to detect abnormalities compared to SPECT was 78% if borderline and abnormal results were expressed as true-positive cases. The specificity was 67%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866484 TI - Cytogenetic investigations from lymphocyte cultures of patients with probable Alzheimer's disease. AB - Chromosome investigations were carried out on lymphocyte cultures of 21 patients with probable Alzheimer's disease in comparison to an age-matched control group of 11 healthy subjects. Different cytogenetic parameters were analyzed: sister chromatid exchanges, polyploid mitoses, mitotic activity and secondary chromosomal aberrations such as gaps, breaks and exchanges. Only the average rate of sister chromatic exchanges was slightly decreased in patients (8.4 +/- 1.7; control group: 10.4 +/- 2.1). There were interindividual differences of values for each of the cytogenetic parameters analyzed, but these were not related to the onset, duration or severity of dementia. PMID- 7866485 TI - A case-control study of Alzheimer's disease in Japan--significance of life styles. AB - A case-control study of Alzheimer's disease was conducted in Japan; it involved 60 cases matched for sex and age with two resident controls each. Life-style was particularly highlighted in this study. Among many factors, 5 were accepted as significant risk factors: psychosocial inactivity, physical inactivity, head injury, loss of teeth and low education. A multiple logistic model was applied in order to evaluate synergism of major factors. Compared with those who have none of the factors, those who have all were 934.5 times more liable to develop Alzheimer's disease. Risk factors are not only useful for etiological studies but they give clues to identify high-risk individuals, and by eliminating these factors, the studies may also be applicable in the primary and the secondary prevention of this tragic disease. PMID- 7866486 TI - Transcranial Doppler sonography in dementia of Alzheimer type. AB - The intention of this study was to examine the relation of clinical variables and cognitive dysfunction to cerebrovascular blood flow in a sample of patients with Alzheimer's disease without any sign or symptom of cardiovascular or cerebrovascular disease. The patients met DSM-III-R criteria for dementia of Alzheimer type. Blood flow velocities in the anterior, middle (MCA) and posterior cerebral arteries were recorded using transcranial Doppler sonography. Several psychometric tests including the Mini-Mental State Examination (MMSE) were performed. The patients' age correlated significantly with the systolic flow velocity in the left MCA (r = -0.57) explaining 24% of the total variance; there was a reduction of the mean flow velocity of 0.7 +/- 0.2 mm/s for every additional year. The MMSE correlated significantly with the systolic flow velocity in the left MCA (r = 0.62) explaining 29% of the total variance. The correlations of flow velocities with age indicate that even in very old patients there is a progressive reduction of cerebral blood flow velocities. The independent negative correlations of flow velocities with cognitive dysfunction indicate that there are progressive cerebrovascular flow reductions in the course of Alzheimer's disease. Both facts should be taken into account when Alzheimer patients are compared with other samples. PMID- 7866487 TI - Language impairment and rate of cognitive decline in Alzheimer's disease. AB - There is growing evidence that AD consists of different subtypes, and that language is a pertinent factor to identify a subgroup with a fast rate of cognitive decline. We report the first results of a longitudinal study in which we compared two groups of patients with probable AD. The main result showed that a subgroup with stable MMSE scores during a 1-year follow-up period had an impairment in language domains which are usually preserved until an advanced stage of the disease. It is proposed that this group may correspond to a variety of AD who, in addition to symptoms of AD, present characteristics of primary progressive aphasia. In other respects, we underscore that the high loading in language-mediated tasks of the MMSE makes it a poor index to accurately measure the rate of cognitive decline. PMID- 7866488 TI - A Scottish record linkage study of risk factors in medical history and dementia outcome in hospital patients. AB - The relative risk (RR) of acquiring a hospital diagnosis of dementia was estimated in 101,104 patients (1 in 25 fraction) randomly selected from total admissions to Scottish general hospitals between 1968 and 1977. The patients were allocated to putative at-risk groups according to main diagnosis at time of index admission, and RR of dementia (ICD 9,290) was contrasted between ten risk groups and a reference group. Record linkage was used to reduce admission episodes to individual cases, to link general and psychiatric Scottish Morbidity Records (SMR 1 and SMR 4), to identify subsequent admission diagnoses of dementia, and to establish person-years-at-risk for each case by linking to the Registrar General's mortality file. For males, RR was significantly increased in the 'hypertensive' risk group (RR 3.88:95% CI 2.18-9.89: p < 0.05) and was significantly reduced in the 'arterial disease' risk group (RR 0.57:95% CI 0.34 0.95: p < 0.05). There was a trend towards increased risk in the cerebrovascular category. For females, RR was significantly reduced in the 'cancer' risk group (RR 0.46:95% CI 0.34-0.63: p < 0.05). There was no evidence of significant alteration in RR in a number of other possible risk groups (endocrine, head injury, CNS/NS disease, ischaemic heart disease, peptic ulcer). Morbidity registers provide access to large data sets of low reliability. No attempt was made to distinguish between Alzheimer's disease and multi-infarct dementia cases, which limited scope for comparison with studies focused on Alzheimer's disease. Previous reports positive associations between head injury, thyroid disorder, and subsequent Alzheimer's disease were not replicated. PMID- 7866489 TI - Dementia in the oldest-old: quantitative analysis of 12 cases from a psychiatric hospital. AB - To examine the neuropathological characteristics of senile dementia of the Alzheimer type (SDAT) in very old people, we performed a quantitative analysis of the distribution of neurofibrillary tangles and senile plaques in the brains of 12 demented patients aged from 96 of 104 years. The hippocampal formation and the inferior temporal cortex displayed numerous neurofibrillary tangles in most cases, whereas the superior frontal cortex was relatively spared. The only statistically significant difference between demented and control cases was in the density of neurofibrillary tangles in the CA1 field of the hippocampus. High senile plaque densities were observed in the cerebral cortex and were correlated with the duration of SDAT. These results confirm the crucial role of the hippocampus in the neuropathological diagnosis of SDAT in oldest-old patients. Furthermore, they suggest that senile plaque formation may be a pathological hallmark of severe SDAT in this particular age group. PMID- 7866490 TI - Designing quality into health care information systems. PMID- 7866491 TI - Orienting health care information systems toward quality: how Group Health Cooperative of Puget Sound did it. AB - BACKGROUND: Group Health Cooperative of Puget Sound (GHC), a large staff-model health maintenance organization based in Seattle, is redesigning its information systems to provide the systems and information needed to support its quality agenda. PLANNING PROCESS: Long-range planning for GHC's information resources was done in three phases. In assessment, interviews, surveys, and a benchmarking effort identified strengths and weaknesses of the existing information systems. We concluded that we needed to improve clinical care and patient management systems and enhance health plan applications. In direction setting, we developed six objectives (for example, approach information systems in a way that is consistent with quality improvement principles). Detailed planning was used to define projects, timing, and resource allocations. MAJOR EFFORTS: Some of the most important efforts in the resulting five-year plan include the development of (1) a computerized patient record; (2) a provider-based clinical workstation for access to patient information, order entry, results reporting, guidelines, and reminders; (3) a comprehensive set of patient management and service quality systems; (4) reengineered structures, policies, and processes within the health plan, supported by a complete set of integrated information systems; (5) a standardized, high-capacity communications network to provide linkages both within GHC and among its business partners; and (6) a revised oversight structure for information services, which forms partnerships with users. CONCLUSIONS: A quality focus ensured that each project not only produced its own benefits but also supported the larger organizational goals associated with "total" quality. PMID- 7866492 TI - TQM information systems: an elusive goal. AB - BACKGROUND: An information support system is needed to locate, integrate, and present data to track and communicate the progress of quality efforts. Bethesda Hospital's executive information system (EIS) has been developed and refined on an ongoing basis to support a variety of total quality management (TQM) functions. PROCESS IMPROVEMENT TEAMS: One basic area where information systems must support TQM is in the availability of data for use by process improvement teams; without such support the entire process of data gathering and analysis would often be prohibitively difficult. Teams also need data to evaluate the results of changes to the improved process. DAILY CONTROL/PROCESS MANAGEMENT: Once core and critical work processes are identified and improvement targets are set, a system of interlinking measures can be established to allow the monitoring and improvement of the processes. SIMULATION MODELING: Models have been used to support and facilitate design or redesign of major processes. CONTINUOUS OPERATIONAL ASSESSMENT AND RESPONSE SYSTEM: The purpose of this decision support system is to monitor a department's core processes and to provide data and a process for quick response to environmental changes. CONCLUSION: The use of information services to support tracking systems, process improvement teams, Hoshin planning, daily control/process management, simulation modeling, and a continuous operational assessment and response (COAR) system has been an integral part of the TQM effort at Bethesda Hospital. PMID- 7866493 TI - Developing a clinical information system: the role of the chief information officer. AB - BACKGROUND: Chief information officers (CIOs) must play a pivotal role in the formation and implementation of a clinical information system, the subset of an organizational information system that deals specifically with support of clinical care activities. MAJOR ELEMENTS OF A CLINICAL INFORMATION SYSTEM: Major elements include the applications software, technology and data architecture, databases, and analysis. The organizational structures and processes that manage the development of improvement activities, including the clinical information system itself, are just as vital to the design of an information system as the hardware and software. THE ROLE OF THE CIO: To develop, sustain, and advance an information infrastructure, the CIO must help establish certain organizational precursors, such as medical staff involvement, experience with quality improvement, and ability to meet data needs. The CIO must then work with the senior administrative and medical leadership in developing a vision for the information system. The CIO must also create new roles and knowledge for information system and medical staff members. Interaction between information services and medical staff is vitally important to the success of a clinical information system. Organizational committees and structures that Brigham and Women's Hospital in Boston put in place to formalize the relationship between information systems and medical staff include the Clinical Initiative Development Program and the Center for Applied Medical Information Systems Research. CONCLUSION: Improving the clinical management of care and the efficacy of care processes involves complex changes in organizational culture and processes, medical practice and information system applications, technologies, staff, and data. PMID- 7866494 TI - Educating executives to integrate information management with quality improvement: a case study. AB - BACKGROUND: Hamot Health Foundation has been committed to and active in continuous quality improvement (CQI) since 1990. These activities have progressed from introductory quality education to application of practical CQI initiatives with the overall objective to improve the quality of patient care. During 1993, the CQI process began to focus on identifying processes requiring care at Hamot. It took shape as a five-step action planning process that focused on data to identify goals and areas for improvement. To accomplish our goal of improving the delivery of care by trimming unnecessary processes, educating Hamot's leaders in information management and decision support became a critical component in the quality improvement effort. CASE STUDY: This article describes the educational program established for vice presidents and service line managers who report to the executive vice president. It also describes how the program was designed to stimulate the use of decision support tools to meet organizational objectives. As a result of this program's success, all service lines are using decision support to support continuous quality improvement. PMID- 7866495 TI - Information management in the age of managed competition. AB - BACKGROUND: Today's information requirements differ from those of the past, in terms of both the internal and external reporting needs of health care organizations. Demands for information are currently generated by physicians, quality managers, total quality management (TQM) teams, marketing staff, financial managers, regulators, insurance plans, accreditation agencies, purchasers, coalitions, and other customers. DISCUSSION: Health care organizations respond to these demands in different ways, depending on their size and type. Six aspects of information needs that would be relevant under managed competition are analyzed: standardization, linkages among data banks, risk adjustment, comprehensive institution-based indicators and information systems, comprehensive population-based indicators and information systems, and methods for protecting confidentiality of patient records. RECOMMENDATIONS: Six recommendations to hospitals/managed care plans that decide to establish information management systems are made: set goals, set priorities, describe current system, identify external data sources, develop (a plan), and check back (reassess). PMID- 7866496 TI - Safeguarding the confidentiality of automated medical information. AB - BACKGROUND: Information about encounters between patients and physicians, nurses, and other caregivers is recorded on paper and in computer databases. Caregivers are expected to respect the confidential nature of patient information. Yet quality management programs, for example, entail systematic, efficient collection of information extracted from patient case files. Compiling "report cards" on managed care networks necessitates access to aggregated information on episodes of care and their outcomes. Regional provider networks; the development of comprehensive computerized patient records; and the dependence of health care reform on large-scale, highly distributed databases make the patient record even more vulnerable. Each organization must assess whether its protection of patients' privacy is sufficient. AN INFORMATION SECURITY PROGRAM: A logical first step in devising such a program is to establish the necessary policies, which are prerequisites to the proper development of computer systems. A policy should address such issues as the authorized access needs to sensitive information and limitations concerning secondary use; the application of technical, procedural, physical, and personnel safeguards; and the dissemination of information. Information managers should seek opportunities to install commercially secure products that meet their security requirements. CONCLUSIONS: Top management, information systems planners, and quality improvement leaders must jointly determine policies that satisfy the duty to preserve patients' confidentiality, foster the most effective use of information in the patient record, and avoid overly restrictive policies that would impede total quality management. PMID- 7866497 TI - Health care information systems--building on the experiences of industry: an interview with A. Blanton Godfrey. Interview by David C. Kibbe. PMID- 7866498 TI - Planning a community health information network: an interview with David E. Garets and Cheryl Juntunen. Interview by Maggie Kennedy. PMID- 7866499 TI - Interdependence of the hue, value, and chroma in the middle site of anterior human teeth. AB - PURPOSE: This study examines how the color coordinates of human teeth are related to each other and describes a mathematical relationship between Hue, Value, and Chroma of the middle site of anterior teeth. MATERIALS AND METHODS: The color coordinates obtained from a previous instrumental survey of the colors of vital teeth (see Goodkind and Schwabacher) were examined statistically, and equations were sought to describe their distribution in color space. The resulting single equation was applied to the colors of 100 extracted teeth. RESULTS: Correlations between Hue, Value, and Chroma were not significant for incisal and cervical sites. For the middle site, these Munsell color coordinates were highly correlated and closely confined to a planar region of the color space, described by a single equation. CONCLUSIONS: Human tooth color distribution seems to be relatively simple, at least for the middle site. It seems possible that a systematic method of shade selection (see Goodkind and Loupe) can be made available. PMID- 7866500 TI - Digital imaging of occlusal contacts in the intercuspal position. AB - PURPOSE: The purpose of this study was to develop an approach to the measurement of occlusal contact area and location using digitized video images of occlusal records. MATERIALS AND METHODS: Five occlusal records in the intercuspal position were made using a polyvinylsiloxane material on five subjects with intact, natural dentition. In regions of occlusal contact, the material showed a minimal film thickness without perforation. A dental cast of the mandibular arch was video digitized and followed by digitization of each of the five occlusal records in place on the cast. An impression of a calibration stepwedge was video digitized to provide the relationship between impression material thickness and pixel density. RESULTS: Contact surface areas ranged from 0.02 to 3.16 mm2 between subjects. The contact positions on a single tooth determined in five records from a single individual showed coefficients of variation between 7.4% to 36.1%. Large variations in contact size were found in this group of five records from a single individual (coefficient of variation ranged from 10.8% to 156.7%). The large difference in contact size between records may be due to variations in biting force at the time the records were made. When the cast position was changed and records redigitized, the mean area of the contact was not significantly different (P > .20) from measurements at the original position. CONCLUSIONS: For the small sample evaluated, a large variation in occlusal contact size was found in the five records. The occlusal contact location was consistent in the five records. The measurement method developed seems to provide reliable measures of occlusal contact surface area and location. PMID- 7866501 TI - A convenient method for guarding against localized mucositis during radiation therapy. AB - Metal restorations, such as full gold crowns and dental implants, can cause forward and back scatter radiation during radiation therapy with a dose enhancement to adjacent tissues. Mucositis, one of the most common complications of the radiation treatment of oral, as well as other head and neck malignancies can result. A method for constructing a buccolingual guard in the clinical setting using hydroplastic material is described. The guard can be easily oriented and adapted to an existing radiation stent, adding positional stability and patient comfort. When adequate thickness of material is used, the guard can attenuate forward and back scatter radiation, separate the adjacent tissues from metal restorations, and protect the oral mucosa from localized incidents of mucositis. PMID- 7866502 TI - Restoring a failed prefabricated post and core with a sleeve casting: a clinical report. AB - A clinical case is described, and a technique is explained for making a custom sleeve cast post and core to salvage a fractured crown previously treated with an unretrievable prefabricated post. The restorative problem was to design and fabricate some sort of cast post and core that could be cemented to the remaining post. The amalgam and cement in the pulp chamber and coronal portion of the root canal were carefully removed so that a direct pattern could be made to form a tube which would surround the coronal part of the existing post like a sleeve. This sleeve casting was designed to provide attachment for a core to support a new restoration. This direct pattern technique results in a retained core that joins the already cemented post and provides a sound core for the retention of a new crown. PMID- 7866503 TI - An evaluation of fit in osseointegrated implant components using torque/turn analysis. AB - PURPOSE: The accurate and passive fit of dental prostheses supported by endosseous implants is of primary importance in securing long-term restorative success. In the clinical setting, adequate visual and radiographic assessment of joined implant components can be limited. Mechanical engineering principles show a linear relationship between tightening and the degree of rotation of a precision bolted assembly. At a constant torque, with certain variables controlled, a threaded fastener should return to the same rotational end position on repeated tightenings. This study evaluated the terminal screw positions of joined implant components as a potential aid to the clinician in confirming the fit of a fixed and removable prosthesis. There were three areas of experimental inquiry: (1) How reproducible are the various clinical means by which torque is applied to the fastening screws, both in absolute and relative value? (2) How reproducible are the rotational end positions of the gold (attachment) and titanium (center) screws when a controlled torque is applied? (3) Do changes in screw position occur as a function of the magnitude of artificially introduced discrepancies? MATERIALS AND METHODS: Three different torque delivery devices were evaluated: a hand-held screwdriver (DIB 048; NobelpharmaUSA, Chicago, IL), a manual torque wrench (DIA 250; NobelpharmaUSA), and an electronic Torque Controller (DEA 020; NobelpharmaUSA), using a calibrated torque measuring dynamometer (Magtrol, Inc, Buffalo, NY). The reproducibility of turning limits were determined for both the titanium and gold screws contained in five Branemark implant assemblies. Each assembly was subjected to six trials, tightening to recommended torque. The position of each screw head was recorded with a special scribe on acetate sheets and transferred to graph paper. Five implant assemblies were invested in dental stone within a die form mold. A casting was made supported by three implant analogues. Stainless steel shims of 12.7-microns, 25.4 microns, 38.1-microns, and 50.8-microns thickness were used to create impingement and space discrepancies. Controlled trials were conducted, and changes in rotational limits for each screw were recorded. RESULTS: The following values were measured, intending to achieve a torque of 10 Ncm, based on 10 trials for each implement: hand driver, 6.48 (+/- 0.85) Ncm; torque wrench, 7.77 (+/- 0.56) Ncm; and the Torque Controller, 8.54 (+/- 0.19) Ncm. The electronic Torque Controller proved to be the most reproducible instrument and was selected as the delivery vehicle for the remainder of the study. The titanium center screws had a rotational limit that was reproducible to within 0.6 degrees (+/- 0.2 degrees). For the gold screws, it was found that at least two trials had to be conducted for each assembly before the rotational limits conformed to a reproducible position within 1.85 degrees (+/- 1.87 degrees). A linear relationship of approximately 0.9 degrees/micron was observed between the changes in rotational limit and each subsequent shim thickness. CONCLUSIONS: This study suggests that screw position can be an indicator of fit in dental implant prostheses if the end point of screw rotation is adequately indexed, specific to each assembly and screw. PMID- 7866504 TI - Development of a radiopaque, autopolymerizing dental acrylic resin. AB - PURPOSE: Current prosthetic acrylic resins are radiolucent and cannot be imaged using standard radiographic techniques. If accidentally impacted or ingested, delays in localizing or removing the foreign body may be life-threatening. The purpose of this study was to evaluate the influence of an experimental radiopaque additive, triphenyl bismuth (TPB), on polymethyl methacrylate resins formulated for dental use. We also investigated methods to improve TPB-containing resin microbeads and optimize processing variables for specimen fabrication in autopolymerizing resin systems. MATERIALS AND METHODS: Selfcured samples of experimental resins were prepared containing 0% to 27% TPB and were tested according to American National Standards Institute/American Dental Association and International Organization for Standardization performance standards. A control group and two commercial provisional crown and bridge resins were used for comparison. RESULTS: The standard of radiopacity (> or = aluminum radiopacity) is met at TPB levels of > or = 14.5%. The control resin had a greater transverse deflection compared with the TPB-resin groups, but deflection was within standard limits for all resins. Polishability, color stability, and solubility were unaffected by TPB, whereas sorption decreased, although not significantly, at higher TPB levels. Translucency decreased at 27% TPB, and specimens containing 0% to 20% TPB were transparent. A tendency to entrain air bubbles, because of the hydrophobicity of TPB, resulted in increased susceptibility to brittle failure at the higher TPB levels. Solubility slightly exceeded American Dental Association standards for all TPB-resins and the control. All other performance standards were acceptable for resins containing 0% to 20% TPB. CONCLUSIONS: At concentrations that provide a diagnostic level of radiopacity, TPB does not significantly alter required performance and processing properties. Thus, TPB is capable of commercially acceptable performance as a radiopacifying additive for dental acrylics. PMID- 7866505 TI - Gypsum compatibility of antimicrobial alginates after spray disinfection. AB - PURPOSE: This investigation examined the gypsum compatibility of two antimicrobial alginates after spray disinfection. Subjective compatibility evaluations were compared with objective quantitative profilometer readings of gypsum cast surface roughness. MATERIALS AND METHODS: COE Hydrophilic Gel Alginate, Jeltrate Plus, Antimicrobial Alginate, and their nonantimicrobial counterparts, Coe Alginate and Jeltrate Plus, were used in this study. After spray disinfection with water (control), Alcide LD, Biocide, OMC II, and 0.5% NaOCI, impressions of the American National Standards Institute/American Dental Association (ANSI/ADA) specification no. 18 detail reproduction die and impressions made simultaneously of a smooth glass die were cast in Microstone, Silky-Rock, and Die-Keen. Five specimens were made for each alginate/disinfectant/gypsum combination for a total of 300 samples each for both the subjective and objective analyses. For the subjective analysis of gypsum compatibility, the specimens made from the ANSI/ADA specification no. 18 test die were evaluated by using a 1-to-4 visual rating system at magnification x12. For the objective analysis, the arithmetic average surface roughness of each specimen made from the smooth glass die was recorded three times with a 200-mg skidless stylus instruments. RESULTS: The results of the ANSI/ADA specification no. 18 testing for gypsum compatibility showed that 11 of 60 possible combinations did not pass the test. All impressions made with nonantimicrobial COE Alginate passed the test regardless of the disinfectant/gypsum combination. The results of the three-factor analysis of variance for the subjective and objective analyses showed significant interactions between alginates, disinfectants, and stones at the P < .05 level. To further delineate these differences, unpaired t tests (P < .05) within brands for each disinfectant/gypsum combination were performed. CONCLUSIONS: The addition of 1% chlorhexidine diacetate to COE Hydrophilic Gel Alginate has decreased its compatibility with the dental stones and disinfectants tested when compared with its nonantimicrobial counterpart. In terms of gypsum compatibility, the nonantimicrobial COE Alginate was compatible with all disinfectant and gypsum combinations tested. The addition of 1.70% didecyldimethyl ammonium chloride to Jeltrate Plus Antimicrobial Alginate has increased its compatibility with all the dental stones tested. A strong positive correlation (r = 0.7398) was found between visual gypsum compatibility evaluation scores and surface roughness of gypsum casts. PMID- 7866506 TI - Endotoxin affinity for provisional restorative resins. AB - PURPOSE: This study compared the relative affinity of Porphyromonas gingivalis and Escherichia coli endotoxin, bacterial cell envelope lipopolysaccharide (LPS), for three provisional resins. MATERIALS AND METHODS: As-polymerized and pumiced polymethyl methacrylate and polyethyl methacrylate resin discs were exposed to 1,000 endotoxin U/mL P. gingivalis or E. coli LPS in water for 24 hours at 37 degrees C, whereas control discs were placed in LPS-free water. LPS-treated discs were transferred at 24-hour intervals to fresh, LPS-free water for up to 96 hours, and the incubated eluates were tested for the presence of LPS. RESULTS: Initial adherence of P. gingivalis LPS to as-polymerized and pumiced-finish resin was a function of resin type, but surface characteristics modified adherence levels. When steady rates of elution were reached at 72 to 96 hours, as polymerized specimens released significantly greater LPS levels than pumiced samples. Comparison of initial adherence of P. gingivalis and E. coli LPS with pumiced resins showed that adherence was based on a combination of LPS and resin type. P. gingivalis LPS had a greater relative affinity for polyethyl methacrylate, and E. coli LPS has a greater relative affinity for polymethyl methacrylate. Regardless of resin type, P. gingivalis LPS eluted at levels greater than E. coli LPS. CONCLUSIONS: The affinity of LPS for provisional resins seems to be a function of selective interactions based on the chemical nature of the resin, the surface finish of the resin, and the molecular structure of the LPS. PMID- 7866507 TI - A systematic approach to definitive planning for osseointegrated implant prostheses. AB - Thoughtful design selection is crucial for the perpetual success of any dental implant restoration. This article reviews treatment considerations specific to the postsurgical presentation of the implant patient. Deviations from the originally planned design may be necessary at this time. Indications for the selection of specific prosthetic modalities are offered in a sequence of paradigms to support the cognitive skills of the inexperienced clinician. PMID- 7866508 TI - The prosthodontic management of endodontically treated teeth: a literature review. Part I. Success and failure data, treatment concepts. AB - Part I of this three-part literature review discusses the incidence of endodontic treatment required after prosthodontic procedures, whether crowns are needed on endodontically treated teeth, the primary purpose of posts, the causes of post and core failure, root fracture incidence data, and post design considerations. Pertinent questions are addressed based on the past 25 years of dental literature. PMID- 7866509 TI - A comprehensive approach to die trimming. AB - Proper trimming of stone dies is an essential step in fixed prosthodontics. Die trimming requires meticulous technique and a thorough understanding of required elements in die design. By dividing the die into three zones, die contour requirements can be better understood, discussed, and demonstrated. A two-step technique provides optimal results, incorporating a logical plan with the use of proper magnification and illumination. PMID- 7866510 TI - A direct provisional restoration for decreased occlusal wear and improved marginal integrity: a hybrid technique. AB - A direct technique for the fabrication of provisional restorations is described. Occluding surfaces of the provisional restoration are veneered with a light-cure composite resin for increased wear resistance and improved occlusal stability. Also described is a method for reestablishing the provisional restoration's margins to achieve optimal tissue health. PMID- 7866511 TI - Detection of ribose-methylated nucleotides in Pyrodictium occultum tRNA by liquid chromatography--frit-fast atom bombardment mass spectrometry. AB - Ribose-methylated dinucleotides of the type NmpN' derived from digestion of tRNA with RNase T2 were separated and characterized by directly combined liquid chromatography--mass spectrometry (LC-MS) with a continuous-flow frit-fast atom bombardment (frit-FAB) interface. Prediction of NmpN' peaks was readily made by comparison of the LC profile with that of comparative nuclease P1 digest. The identity of the candidate peaks including NmpN' was further recognized by the mass spectra, in which NmpN' showed intense molecular-related ions, in addition to sequence-specific fragment ions, to verify the chemical structures in both positive- and negative-ion modes. The method was applied to screening NmpN' (and NmpN' mpN") in tRNA from the extremely thermophilic archaeon Pyrodictium occultum. PMID- 7866512 TI - Determination of total dopamine, R- and S-salsolinol in human plasma by cyclodextrin bonded-phase liquid chromatography with electrochemical detection. AB - A reliable and sensitive high-performance liquid chromatographic (HPLC) method is presented for the determination of total (free and conjugated) plasma dopamine and the enantiomers R- and S-salsolinol. Plasma is purified on two cartridges, containing primary and secondary amines and phenylboronic acid. Dopamine, R- and S-salsolinol are then separated by HPLC using a beta-cyclodextrin-OH phase column. The eluate is monitored electrochemically, without further purification nor derivatization. The method is suited for routine analysis. It allows the detection of total (free and conjugated) dopamine and R- and S-salsolinol in human plasma in concentrations as low as 0.02 ng/ml plasma. The sensitivity is sufficient to measure the naturally occurring levels of salsolinol. PMID- 7866513 TI - Simultaneous determination of D- and L-amino acids in the nervous tissues of crustaceans using precolumn derivatization with (+)-1-(9-fluorenyl)ethyl chloroformate and reversed-phase ion-pair high-performance liquid chromatography. AB - After the derivatization of D- and L-amino acids with (+)-1-(9-fluorenyl)ethyl chloroformate, nineteen amino acids were separated into their D- and L enantiomers and from other physiological amino compounds by reversed-phase ion pair high-performance liquid chromatography. The separation was performed by three separate runs differing in mobile phase compositions and gradient profiles. Tyrosine, tryptophan and cysteine could not be detected because of their weak reactions with the derivatization reagent. Of seven D-amino acids found in the crustacean nervous tissues and eyes, D-alanine, D-arginine and D-aspartate were the most abundant and widely distributed. PMID- 7866514 TI - Automated simultaneous isolation and quantitation of labeled amino acid fractions from plasma and tissue by ion-exchange chromatography. AB - In order to trace metabolic pathways of amino acids in the body, a known labeled amount of an amino acid is infused. Dilution in the body pool is measured, using the specific activity and calculated by dividing the labeled amount of an amino acid (tracer) by its total pool (tracer + tracee). This paper describes a method, which combines fractionation and quantitation of multiple amino acids in one chromatographic run. To achieve this, we performed a classical amino acid ion exchange separation on standard HPLC equipment. The column effluent was divided continuously into two solvent streams using a rapidly switching, pump controlled "split-valve". The main part (90%) was directed to a computer controlled fraction collector, while the remaining 10% was mixed with o-phthaldialdehyde reagent after which fluorescence was measured. Using this system, 10-1000 microliters of deproteinized plasma, representing a maximum of 50 nmol of each amino acid, could be fractionated and quantitated in the same chromatographic run. In addition to optimal counting efficiency of an off-line radioactivity counter, it enabled easy measurement of the specific activity of multiple amino acid tracers. PMID- 7866515 TI - High-performance liquid chromatographic method for the determination of insulin synthesis in biological systems. AB - This paper reports a two-step high-performance liquid chromatographic procedure which permits the study of the incorporation of [3H]leucine into insulin in biological systems. The first step of the procedure was size exclusion chromatography, performed on a GPC-100 column, which was eluted with 0.1 M KH2PO4 methanol (9:1, v/v). By this step the bulk of both protein and radioactivity was separated from tritiated insulin. The second step, which employs reversed-phase chromatography on an octadecylsilyl column, permits the separation of insulin from other contaminants by means of a linear gradient of acetonitrile. This simple and reproducible method was employed to test insulin synthesis in cultured human retinoblastoma Y79 cells. PMID- 7866516 TI - Quantitation of the glycation intermediate 3-deoxyglucosone by oxidation with rabbit liver oxoaldehyde dehydrogenase to 2-keto-3-deoxygluconic acid followed by high-performance liquid chromatography. AB - A simple and sensitive method for the detection of 3-deoxyglucosone was developed using oxidation with crude oxoaldehyde dehydrogenase to 2-keto-3-deoxygluconic acid followed by high-performance liquid chromatography (HPLC). Oxoaldehyde dehydrogenase was prepared from rabbit liver and partially characterized. 2-Keto 3-deoxygluconic acid produced from 3-deoxyglucosone by oxoaldehyde dehydrogenase was derivatized with 1,2-diamino-4,5-methylenedioxybenzene, and the fluorescent products were detected and quantitated by HPLC using a solvent containing borate. In the presence of borate, 2-keto-3-deoxygluconic acid was completely separated from N-acetylneuraminic acid. The detection limit of 3-deoxyglucosone was 2.5 pmol/injection (10 microliters) at a signal-to-noise ratio of 3. This method was used to confirm the inhibitory effect of aminoguanidine on glycation. PMID- 7866517 TI - Quantitative analysis of DNA aberrations amplified by competitive polymerase chain reaction using capillary electrophoresis. AB - We compared the use of capillary electrophoresis (CE) in a polymer network with the use of slab gel electrophoresis for the quantitative analysis of polymerase chain reaction (PCR)-amplified DNA samples. We quantified residual lymphoma cells carrying a translocation between chromosomes 14 and 18, in consecutive patient peripheral blood samples that were amplified by competitive PCR. For CE analysis we used a 4% linear polyacrylamide network. Results show that the calculated number of translocations in patient samples using both analyses were comparable. We conclude that CE is a sensitive, non-radioactive, fast and accurate method for quantitation of competitive PCR products. PMID- 7866518 TI - Simultaneous assay of cocaine, heroin and metabolites in hair, plasma, saliva and urine by gas chromatography-mass spectrometry. AB - As part of an ongoing research program on the development of drug detection methodology, we developed an assay for the simultaneous measurement of cocaine, heroin and metabolites in plasma, saliva, urine and hair by solid-phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS). The analytes that could be measured by this assay were the following: anhydroecgonine methyl ester; ecgonine methyl ester;. ecgonine ethyl ester; cocaine; cocaethylene; benzoylecgonine; cocaethylene; norcocaethylene; benzoylnorecgonine; codeine; morphine; norcodeine; 6-acetylmorphine; normorphine; and heroin. Liquid specimens were diluted, filtered and then extracted by SPE. Additional handling steps were necessary for the analysis of hair samples. An initial wash procedure was utilized to remove surface contaminants. Washed hair samples were extracted with methanol overnight at 40 degrees C. Both wash and extract fractions were collected, evaporated and purified by SPE. All extracts were evaporated, derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane (TMCS) and analyzed by GC-MS. The limit of detection (LOD) for cocaine, heroin and metabolites in biological specimens was approximately 1 ng/ml with the exception of norcodeine, normorphine and benzoylnorecgonine (LOD = 5 ng/ml). The LOD for cocaine, heroin and metabolites in hair was approximately 0.1 ng/mg of hair with the exception of norcodeine (LOD = 0.3 ng/mg) and normorphine and benzoylnorecgonine (LOD = 0.5 ng/mg). Coefficients of variation ranged from 3 to 26.5% in the hair assay. This assay has been successfully utilized in research on the disposition of cocaine, heroin and metabolites in hair, plasma, saliva and urine and in treatment studies. PMID- 7866519 TI - Determination of 1-methoxy-2-propanol and its metabolite 1,2-propanediol in rat and mouse plasma by gas chromatography. AB - A method utilizing capillary GC and flame ionization detection was developed for the simultaneous determination of 1-methoxy-2-propanol (propylene glycol monomethyl ether; PGME) and its metabolite 1,2-propanediol (propylene glycol; PG) in rat and mouse plasma. The calibration graphs for rat and mouse plasma were linear with correlation coefficients at > 0.997 over the range 2-700 micrograms/ml. The limit of quantification was ca. 2 micrograms/ml (2 ng on column) for both compounds in plasma of each species. The ranges of the precision and accuracy for PGME were 2.8-8.8% and 3.2-13%, respectively, and for PG were 11 26% and 10-25%, respectively. The recovery of PGME from rat and mouse plasma was ca. 73% and for PG it was ca. 65 and 31% from rat and mouse plasma, respectively. The method was used to study the oral absorption and metabolism of PGME in mice. PGME was readily absorbed and metabolized to PG following oral gavage administration at 90 mg/kg. The maximum concentrations of PGME and PG in plasma were attained at 20 and 30 min following dosing, respectively. PMID- 7866520 TI - Determination of nifedipine in human serum by gas chromatography-mass spectrometry: validation of the method and its use in bioavailability studies. AB - A procedure for the determination of nifedipine in human serum is described. The light-sensitive substance is isolated from serum by liquid-liquid extraction and analyzed using capillary gas chromatography with a mass-selective detector. The validation of the method shows that the extraction recovery is ca. 85%, the limit of detection is 2 ng/ml and the standard deviations of the intra-day precision test range from 5.8 to 7.4% with respect to the concentration. The procedure is highly selective and sensitive. It is especially suited for bioavailability studies because of its stability and high sampling rate. PMID- 7866521 TI - Determination of beta-sympathomimetics in liver and urine by immunoaffinity chromatography and gas chromatography-mass-selective detection. AB - A specific and sensitive method for the determination of several beta-agonistic drugs in liver and urine is described. Following clean-up by immunoaffinity chromatography and two different derivatizations, gas chromatography-mass spectrometry with electron-impact ionization is performed. The immunoaffinity chromatography columns were packed with Sepharose-immobilized polyclonal antibodies raised against the beta-agonist clenbuterol. Owing to the high clean up efficiency of the immunoaffinity column large sample volumes can be used (up to 100 ml urine or 25 gram liver). The immunoaffinity sample pretreatment is highly specific and no further sample pretreatment was necessary. Due to the combination of two different derivatizations only GC-MS with electron-impact ionization is necessary to fulfil legal requirements. The first confirmation step consists of a derivatization reaction between the hydroxyl group of the parent compound and trimethylsilane. The second confirmation method is a derivatization to a cyclic derivative with the hydroxyl group and the aliphatic nitrogen group. Limits of determination in liver as well in urine are at the 10 ng/kg or ng/l (ppt) level with acceptable signal-to-noise ratio. The method is suitable for identification and quantification of trace amounts of several similar beta agonistic drugs either used separately or in combination and can be used also for quantification of clenbuterol in liver with regard to levels exceeding the maximum residue limit (MRL) of 1 microgram/kg (ppb). PMID- 7866522 TI - Determination of metoclopramide and two of its metabolites using a sensitive and selective gas chromatographic-mass spectrometric assay. AB - A modified gas chromatographic-mass spectrometric (GC-MS) assay has been developed to quantitate metoclopramide (MCP) and two of its metabolites [monodeethylated-MCP (mdMCP), dideethylated-MCP (ddMCP)] in the plasma, bile and urine of sheep. The heptafluorobutyryl derivatives of the compounds were formed and quantitated using electron-impact ionization in the selected-ion monitoring mode (MCP, m/z 86, 380; mdMCP, m/z 380 and ddMCP, m/z 380). No interference was observed from endogenous compounds following the extraction of various biological fluids obtained from non-pregnant sheep. Sample preparation has been simplified and the method is more selective and sensitive (2 fold) than our previous assay using electron-capture detection. The limit of quantitation for MCP, mdMCP and ddMCP was 1 ng/ml in plasma, urine and bile, requiring 0.5 ml of sample. This represents 2.5 pg of the analytes at the detector. The standard curves were linear over a working range of 1-40 ng/ml. Absolute recoveries in plasma ranged from 76.5-94.7%, 79.2-96.8%, 80.3-102.2% for MCP, mdMCP and ddMCP, respectively. In urine, recoveries ranged from 56.5-87.8%, 61.5-87.5%, 62.6-90.2% for MCP, mdMCP and ddMCP, respectively. Recoveries in bile ranged from 83.5-100.9%, 78.5 90.5%, 66.9-79.2% for MCP, mdMCP and ddMCP, respectively. Overall intra-day precision ranged from 2.9% for MCP in plasma to 12.6% for mdMCP in bile. Overall inter-day precision ranged from 5.9% for MCP in urine to 14.9% for ddMCP in bile. Bias was the greatest at the 1 ng/ml concentration in all biological fluids ranging from a low of 2.4% for mdMCP in plasma to a high of 11.9% for ddMCP in urine. Applicability of the assay for pharmacokinetic studies of MCP, mdMCP and ddMCP in the plasma and urine of a non-pregnant ewe is demonstrated. PMID- 7866523 TI - Determination of the enantiomers of bunolol in human urine by high-performance liquid chromatography on a chiral AGP stationary phase and identification of their metabolites by gas chromatography-mass spectrometry. AB - A high-performance liquid chromatographic method using a chiral AGP column was developed to screen and determine the enantiomers of bunolol in human urine. The recovery of (+)- and (-)-bunolol from urine was 91.79-95.23% at different concentrations. The coefficients of variation (C.V.) were less than 2.1 and 2.3% for intra- and inter-assays, respectively. Urinary metabolites were detected using GC-MS after derivatization with N-methyl(trimethylsilyl)trifluroacetamide. The influences of pH and modifier on a chiral AGP column were studied. PMID- 7866524 TI - High-performance liquid chromatographic determination of oxodipine enantiomers, a new 1,4-dihydropyridine, applied to stereoselectivity studies in man and dog. AB - A specific and reproducible HPLC method using a Chiral-AGP column and UV detection was developed for the evaluation of the pharmacokinetic profile of oxodipine enantiomers in dog and man. Each enantiomer was determined in plasma in the concentration range 1-400 ng/ml using the internal standard calibration method with linear regression analysis. After extraction of oxodipine and the internal standard at alkaline pH with diethyl ether-n-hexane (50:50, v/v), this method permitted the determination of each enantiomer at levels down to 10 ng/ml in dog plasma and 25 ng/ml in human plasma with sufficient accuracy (relative error < 11%, n = 6) and precision (coefficient of variation < 16%, n = 6). The extracted plasma volume was 500 microliters and after evaporation of the organic phase, the dry residue was dissolved in 100 microliters of water-2-propranol; an aliquot of 80 microliters was injected into the HPLC system. PMID- 7866525 TI - Liquid chromatographic determination of sodium mercaptoundecahydrododecaborate in rat urine and plasma after precolumn derivatization. AB - A high-performance liquid chromatographic (HPLC) method was developed for the determination of disodium mercaptoundecahydrododecaborate (BSH) in biological fluids. Monobromobimane was used as a precolumn derivatizing agent. A stable derivative was obtained. The derivative was separated on a C18 column using reversed-phase ion-pairing chromatography and detected by a spectrophotometric detector at 373 nm. The detection limit was 200 ng/ml (0.1 ppm boron). Calibration curves were prepared for rat urine and plasma samples. The calibration curves were linear in the range of 1 microgram/ml to 100 micrograms/ml for urine samples and 0.2 micrograms/ml to 50 micrograms/ml for plasma samples. PMID- 7866526 TI - Elucidation of the structure of talinolol metabolites in man. Determination of talinolol and hydroxylated talinolol metabolites in urine and analysis of talinolol in serum. AB - The objective of this study was to determine the structure of talinolol metabolites formed and the amounts excreted in urine. Talinolol metabolites in urine were identified by comparing their HPLC retention times and their GC-MS profile with those of previously characterized reference compounds. The metabolites were quantified by HPLC with a normal-phase silica column, a single chloroform extraction and UV detection. Less than 1% of an administered dose was found in urine as hydroxylated talinolol. Other metabolites could be excluded. A sensitive method to determine talinolol in serum and a simple method for analysis of talinolol in urine are described. These methods were found to be precise and accurate for the measurement of talinolol in samples obtained from patients during chronic talinolol treatment as well as from healthy volunteers after a single dose of talinolol. PMID- 7866527 TI - High-performance liquid chromatographic determination of the new quinolone antibacterial agent DU-6859a in human serum and urine using solid-phase extraction with photolysis-fluorescence detection. AB - A sensitive and specific HPLC method for the determination of DU-6859a (I), a fluoroquinolone antibacterial agent, in human serum and urine was developed. Compound I and the internal standard extracted from serum and urine by means of a Bond Elut C8 LRC cartridge showed recoveries of 96%. The extracts were chromatographed on a reversed-phase column with photolysis-fluorescence detection. This unique detection method was 42.5 times more sensitive than intrinsic fluorescence detection, the limits of detection being in 3.43 ng/ml for serum and 4.35 ng/ml for urine. In addition, I was stable in serum and urine for at least 1 month at -20 degrees C. The proposed method was sensitive and selective enough to apply to pharmacokinetic studies of I in humans after a single oral dose of 100 mg. PMID- 7866528 TI - Determination of D,L-propargylglycine and N-acetylpropargylglycine in urine and several tissues of D,L-propargylglycine-treated rats using liquid chromatography mass spectrometry. AB - An experimental animal model with cystathioninuria was obtained by the injection of D,L-propargylglycine into rats. The concentrations of D,L-propargylglycine in urine, several tissues and serum at different times after the injection were measured by liquid chromatography-mass spectrometry. The propargylglycine accumulated rapidly in several tissues and serum of the rats, and reached its maximum level at about 2 h after the injection. Approximately 21.2% of the administered propargylglycine was excreted in urine. N-Acetylpropargylglycine was identified as a new metabolite of propargylglycine in urine. The concentration of propargylglycine was 100 times that of N-acetylpropargylglycine in urine. PMID- 7866529 TI - High-performance liquid chromatographic method for determination of the metabolism of polyunsaturated molecular species of phosphatidylserine labeled in the polar group. AB - A reversed-phase HPLC method to monitor the incorporation of radiolabeled precursors into the polar group of individual polyunsaturated molecular species of phosphatidylserine (PS) is presented. PS labeled in the polar group was decarboxylated and subsequently converted to trinitrophenyl phosphatidylethanolamine (Tnp-PE), which was separated into its molecular species by reversed-phase HPLC within 90 min, using a gradient of acetonitrile-methanol and ammonium acetate. A major feature of the method is the complete resolution of the stearoyl species, 18:0/20:4 and 18:0/22:6, at ambient temperature. By determining the amount of radioactivity incorporated into each fraction, the metabolism of individual molecular species of PS, and also of PE, labeled in the polar group can be investigated. PMID- 7866530 TI - Determination of cholesteryl 14-methylhexadecanoate in blood serum by reversed phase high-performance liquid chromatography. AB - A simple reversed-phase HPLC method has been developed for the determination of cholesteryl 14-methylhexadecanoate (CMH) in the blood serum. Lipids are extracted from 0.1 ml of blood serum and after centrifugation, the extract is chromatographed and individual cholesteryl esters, including CMH are separated and eluted with an acetonitrile-2-propanol mixture. The quantification of cholesteryl 14-methylhexadecanoate is precise and highly reproducible and the analysis may be completed within 35 min. The level of CMH in the blood of cancer patients appears to be a useful marker of malignant tumors. PMID- 7866531 TI - Ultra-rapid preparation of milligram quantities of the purified polypeptide chains of human fibrinogen. AB - In order to study the epitopes in fibrin towards which monoclonal antibodies are directed we needed the pure individual polypeptide chains of human fibrinogen in reasonable quantity. We report here a simplified, rapid method of separation of high-purity human fibrinogen chains. Following reduction and S-carboxymethylation of human fibrinogen, the sample was injected directly onto a column of the polymeric reversed-phase perfusion packing POROS 20-R2, and the chains were completely resolved in less than 3 min at a flow-rate of 10 ml/min. The capacity was equivalent to that of a similar sized conventional silica-based column. However the throughput was approximately five to ten times as high. The column was durable and robust in day-to-day use. PMID- 7866532 TI - Determination of alpha-tocopherol in plasma and erythrocytes by high-performance liquid chromatography. AB - A reversed-phase high-performance liquid chromatographic method for the determination of alpha-tocopherol in plasma or erythrocytes with photodiode-array detection is described. Using this detector, information about the spectrum, absorption maxima and purity of the peak is obtained. Tocopherol was separated on a 5-microns Spherisorb ODS-2 column with methanol as element at a flow-rate of 1.0 ml/min. As little as 100 microliters of plasma or 150 microliters of erythrocytes can be used for accurate analysis with direct extraction without saponification. The speed, specificity, sensitivity and reproducibility of this technique make it particularly suitable for the routine determination of alpha tocopherol in plasma or erythrocytes. PMID- 7866533 TI - Measurement of nitrite and nitrate levels in biological samples by capillary electrophoresis. AB - Nitrite is one of the products of NO-synthase in biological media. It is slowly oxidized in animals to nitrate. We developed a simple and rapid method to determine simultaneously nitrite and nitrate in biological samples. Capillary ion electrophoresis with direct UV detection at 214 nm was used employing a carrier electrolyte consisting of 10 mM sodium sulfate and an electroosmotic flow modifier. The detection limit in ultrafiltrates of plasma, urine and brain tissue extracts was 25 ng/ml for both compounds. Nitrate levels in human plasma and urine were in the microgram/ml range. Nitrite could not be detected. Rat brain tissue extracts contained detectable amounts of nitrite and nitrate. PMID- 7866534 TI - Application of high-performance liquid chromatography to the determination of vinblastine in Catharanthus roseus. AB - A method for the determination of vinblastine in Catharanthus roseus by HPLC is described. A crude alkaloid extract, obtained by extraction of leaves with toluene, 2% citric or tartaric acid and benzene, was separated by TLC. The vinblastine fraction was cut out and vinblastine was eluted from the sorbent. The amount of vinblastine was determined by HPLC with peak-height measurement. The standard deviation is 0.2 microgram/ml. The detection limit is 0.05 ng of vinblastine in a sample applied to the HPLC column. PMID- 7866535 TI - Determination of nadoxolol in human plasma using reversed-phase high-performance liquid chromatography. AB - A rapid, simple and accurate HPLC method is presented for the determination of nadoxolol in human plasma. Nadoxolol from plasma was successfully purified using an Adsorbex column. The samples were chromatographed on a LiChrosorb RP-18 (10 microns) column with methanol-acetonitrile-phosphate buffer (pH 3.3) (70:20:10) as the mobile phase. Detection was carried out at 254 nm. The method was tested for linearity (from 5 to 25 micrograms/ml), recovery (85%) and precision (C.V. = 4.5%). PMID- 7866536 TI - Simultaneous determination of ormethoprim and sulphadimethoxine in plasma and muscle of Atlantic salmon (Salmo salar). AB - A rapid clean-up and high-performance liquid chromatographic method for the simultaneous determination of ormethoprim and sulphadimethoxine in plasma and muscle of Atlantic salmon (Salmo salar) has been developed. Sample preparation is based on protein precipitation using trichloroacetic acid or methanol for plasma and muscle, respectively. The drugs are separated using a reversed-phase C18 analytical column and phosphate buffer-acetonitrile (80:20, v/v) containing 1 heptanesodiumsulphonate and triethylamine, as mobile phase. Detection was performed at 270 nm. The average recovery of ormethoprim was 97.2% in muscle and 95.7% in plasma, whereas the average recovery of sulphadimethoxine was 86.5% in muscle and 90.2% in plasma. The limit of detection at a signal-to-noise ratio of 3 was 50 ng/g and 30 ng/ml for ormethoprim in muscle and plasma respectively and 30 ng/g and 15 ng/ml in muscle and plasma respectively for sulphadimethoxine. PMID- 7866537 TI - Partial characterization of the molecular species of phosphatidylserine from human plasma by high-performance liquid chromatography and fast atom bombardment mass spectrometry. AB - Phosphatidylserine from human plasma was purified and identified by amino normal phase and octadecylsilyl reversed-phase high-performance liquid chromatography, respectively. The two major molecular species within the human plasma phosphatidylserine, qualitatively determined by negative-ion fast atom bombardment mass spectrometry, are 1-stearoyl-2-oleoyl-sn-glycero-3-phosphoserine and 1-stearoyl-2-arachidonyl-sn-glycero-3-phosphoserine. PMID- 7866538 TI - Simultaneous measurement of the major metabolites of dolasetron mesilate in human urine using solid-phase extraction and high-performance liquid chromatography. AB - A method based on solid-phase extraction and high-performance liquid chromatography (HPLC) has been developed for the simultaneous quantitation of the principal active metabolites of dolasetron mesilate [i.e. MDL 74,156 (II), MDL 102,382 (III) and MDL 73,492 (IV)] in human urine. The method has been validated over the concentration range of 200-5000 pmol/ml for all three metabolites. Within-day and day-to-day coefficients of variation were less than 9 and 14%, respectively, for the three metabolites. The method allowed the simultaneous quantitation of III, IV and II and the evaluation of the urinary excretion of these metabolites in human urine following the administration of dolasetron mesilate. PMID- 7866539 TI - High-performance liquid chromatographic determination of methotrexate, 7 hydroxymethotrexate, 5-methyltetrahydrofolic acid and folinic acid in serum and cerebrospinal fluid. AB - A method for the simultaneous determination of the antifolates methotrexate and 7 hydroxymethotrexate as well as the folates 5-methyltetrahydrofolic acid and folinic acid (5-formyltetrahydrofolic acid) in serum and cerebrospinal fluid (CSF) is described. High-performance liquid chromatography with gradient elution and dual detection (ultraviolet absorption and fluorescence) was used to separate and quantitate the analytes. Serum samples containing high levels of the substances of interest and CSF samples were injected directly onto the HPLC column. For determination of low concentrations, serum samples were subjected to a solid-phase extraction method for clean-up and concentration purposes. The determination limits were 10 ng/ml for both antifolates, 100 ng/ml for folinic acid, and 0.1 ng/ml for the physiologically occurring methylated folate which is about 1/100 the serum concentration in healthy children. The suitability of the method for pharmacokinetic monitoring of high-dose methotrexate therapy combined with leucovorin rescue administered to children with acute lymphoblastic leukemia was demonstrated. Minimum values of the serum folate during treatment ranged from 0.2 to 3.1 ng/ml. Even those very low concentrations could be reliably measured. PMID- 7866540 TI - Assay and single dose pharmacokinetics of a novel systemic acyl coenzyme A cholesterol O-acyltransferase inhibitor, RP 73163, in rat plasma using automated solid-phase extraction with high-performance liquid chromatography. AB - RP 73163, (S)-2-[5-(3,5-dimethylpyrazol-1-yl)pent-1-yl]sulphinyl-4,5 diphenylimidazole (I), is a highly potent in vitro and in vivo inhibitor of acyl coenzyme A cholesterol O-acyltransferase (ACAT) (E.C. 2.3.1.26), and as such it has potential therapeutic use as a cholesterol lowering agent in man. A method has been developed for the extraction and assay of I from rat plasma, using a fully automated solid-phase extraction column (ASPEC) technique, coupled to a reversed-phase HPLC system with detection by native fluorescence. The method has been validated over the concentration range 10-500 ng/ml, with demonstrated linearity, precision and accuracy, the mean limit of detection being 6.6 +/- 1.3 ng/ml. Application of the method to the assay of samples following administration of the compound to male and female rats is reported, together with determined pharmacokinetic parameters. PMID- 7866541 TI - Reversed-phase high-performance liquid chromatographic method for the simultaneous quantitation of the carboxylate and lactone forms of the camptothecin derivative irinotecan, CPT-11, and its metabolite SN-38 in plasma. AB - Irinotecan, also known as CPT-11 (I), is a potent semi-synthetic derivative of 20(S)-camptothecin (CPT). Like all known active derivatives of CPT, the lactone forms of I and its active metabolite SN-38 (II) are reversibly hydrolysed to inactive carboxylate forms. We describe a sensitive and selective HPLC method using the ion-pairing reagent tetrabutylammonium phosphate (TBAP) which allows the simultaneous determination of the carboxylate and lactone forms of I and II in human plasma samples following the precipitation of plasma proteins with an ice-cold mixture of acetonitrile and methanol. The mobile phase was 0.075 M ammonium acetate buffer (pH 6.4)-acetonitrile (78:22, v/v) containing 5 mM TBAP. Separation of the compounds was performed on a radially-compressed C18 column. The limits of quantitation in human plasma were 2 and 10 ng/ml for the two forms of II and I, respectively. In addition, we propose the use of CPT lactone both as an internal standard and as a "watchdog" for sample status. Under unsuitable storage conditions, CPT elutes increasingly in its carboxylate form thereby alerting the operator of possibly erroneous determinations of the concentrations of both forms of I and II. The retention times of the peaks of interest are well separated from the solvent front. This enables the detection of early eluting metabolites. The method was successfully used for monitoring of the two forms of I and II in patients treated with I. PMID- 7866542 TI - Determination of 8-methyl ether of xanthurenic acid in human urine by high performance liquid chromatography. AB - We developed a simple and sensitive assay for the urinary 8-methyl ether of xanthurenic acid (XA-OMe) by high-performance liquid chromatography with fluorescence detection (excitation at 340 nm; emission at 450 nm). Urine samples were diluted with 0.03 M potassium phosphate buffer (pH 6.0) and applied to an octadecylsilane-bonded column (Nucleosil 5C18, 150 x 4 mm I.D.). The mobile phase used was a mixture of this same buffer and acetonitrile (1000:140, v/v). Both direct injection of urine and solvent extraction prior to HPLC were tested and showed a good correlation and sensitivity, although the peak of XA-OMe was occasionally less distinguishable from close peaks in urine from normal controls by the direct injection method. The quantification limit was 5 x 10(-14) mol which was sensitive enough to detect XA-OMe in urine from normal subjects. The method was applied to samples from patients with a deficiency in tryptophan catabolism, xanthurenic acid/3-hydroxykynurenine-uria and showed a striking elevation in urinary XA-OMe excretion. PMID- 7866543 TI - Simultaneous high-performance liquid chromatographic determination of 6 beta hydroxycortisol and cortisol in urine with fluorescence detection and its application for estimating hepatic drug-metabolizing enzyme induction. AB - A simple and sensitive high-performance liquid chromatographic method is described for the simultaneous determination of 6 beta-hydroxycortisol (6 beta OHF) and cortisol (F) in urine. Urine (1 ml) containing fludrocortisone as the internal standard is extracted with ethyl acetate. The extract is washed successively with sodium hydroxide solution and water, and subsequently dried under a stream of nitrogen. The residue is redissolved in methanol. The 6 beta OHF, F and fludrocortisone in the methanol solution are oxidized by cupric acetate and the resulting glyoxal compounds are converted into fluorescent derivatives with 1,2-diamino-4,5-methylenedioxybenzene (DMB). The DMB derivatives of the corticosteroids are separated within 70 min on a reversed-phase column, L Column ODS, using stepwise elution with methanol-acetonitrile-0.5 M ammonium acetate and detected fluorimetrically at 350 nm (excitation) and 390 nm (emission). The lower limits of detection for 6 beta-OHF and F are 1.8 pmol (680 pg) and 2.4 pmol (950 pg)/ml urine (0.6 pmol and 0.8 pmol/100 microliters injection volume), respectively, at a signal-to-noise ratio of 3. This method can be applied to the determination of urinary 6 beta-OHF, and the ratio of 6 beta OHF to F in humans and in rhesus monkeys treated orally with phenobarbital as a hepatic drug-metabolizing enzyme inducer. PMID- 7866544 TI - Simultaneous measurement of nicotinic acid and its major metabolite, nicotinuric acid in urine using high-performance liquid chromatography: application of solid liquid extraction. AB - The concentrations of nicotinic acid (NiAc) and nicotinuric acid (NiUAc), a major metabolite of NiAc, were simultaneously determined in urine using solid-phase extraction (cation-exchange extraction) and reversed-phase high-performance liquid chromatography with ultraviolet detection. The intra- and inter-day precision studies showed good reproducibilities: the coefficients of variations were less than 8.1% for NiAc and 8.8% for NiUAc. The calibration curves were linear (r2 > 0.9934) in the concentration range 10-1000 micrograms/ml. The removal of endogenous interferences in urine by solid-phase extraction presented here is superior to the pretreatment protocols reported previously by other workers. The method was used in a preliminary pharmacokinetic study in rats after intravenous administration of NiAc (5 and 15 mg/kg). PMID- 7866545 TI - Detection of ketorolac enantiomers in human plasma using enantioselective liquid chromatography. AB - A high-performance liquid chromatographic method for the determination of the enantiomers of ketorolac in human plasma has been developed. Plasma samples containing ketorolac were acidified and extracted into diethyl ether. The ethereal extract was evaporated to dryness and the residue reconstituted in mobile phase before injection onto a Chiral-AGP column. The mobile phase was 2 propanol-20 mM potassium dihydrogenphosphate buffered to pH 7 (0.5:99.5, v/v). Detection was by ultraviolet absorbance at 320 nm. The detection limit was 5 ng/ml for each enantiomer. The method has been applied to determine the concentration of ketorolac enantiomers during an infusion of the racemic drug and has proven to be rapid and sensitive. PMID- 7866546 TI - Sensitive high-performance liquid chromatographic determination of chlorpheniramine in human serum using column switching. AB - A sensitive method for the determination of chlorpheniramine in human serum was developed using column-switching high-performance liquid chromatography (HPLC) with ultraviolet detection at 210 nm. The analyte was extracted with diethyl ether from alkalinized serum. After evaporation of the organic layer, the reconstituted residue was analyzed by HPLC using a heart-cut technique. Good recoveries of the analyte from spiked human serum samples were obtained with a coefficient of variation below 7%. A good linear response was obtained for the concentration range 0.5-50 ng/ml, with a correlation coefficient higher than 0.999. The lower limit of quantitation for chlorpheniramine in human serum was 0.5 ng/ml. The method was satisfactorily applied to the determination of chlorpheniramine in human serum after oral administration of chlorpheniramine maleate. PMID- 7866547 TI - Ion-pair solid-phase extraction of cimetidine from plasma and subsequent analysis by high-performance liquid chromatography. AB - An improved method is described for the solid-phase extraction of cimetidine from plasma or serum with subsequent analysis by HPLC. New aspects of the method include protein precipitation with metaphosphoric acid (5%, w/v), followed by selective adsorption of cimetidine and the internal standard ranitidine on the surface of a solid-phase phenyl (PH Bond Elut) column, using octanesulfonate as an ion-pairing agent. Separation was achieved on a LiChrosorb RP-18 column with a mobile phase consisting of acetonitrile-0.01 M phosphate buffer pH 3.0 containing 0.005 M octanesulfonate (22:78, v/v). The intra-assay coefficient of variation varied between 0.7 and 4.0%. The procedure provides cleaner and more stable samples and a better recovery (90 +/- 2.3%) and sensitivity (limit of detection 5 ng/ml and limit of quantitation 25 ng/ml) as compared with previous methods. PMID- 7866548 TI - High-performance liquid chromatographic assay for the simultaneous determination of ethyl clofibrate and clofibric acid in plasma. Evaluation of plasma stability of ethyl clofibrate polylactic nanocapsules in human and rat plasmas. AB - A rapid, sensitive, and selective HPLC assay was developed for the simultaneous determination of ethyl clofibrate and its major metabolite, clofibric acid, in plasma of humans and rats. The assay involves extraction of the compounds into chloroform-isoamyl alcohol (99:1, v/v) from plasma acidified with sulfuric acid. For human plasma, the overall recoveries of ethyl clofibrate and clofibric acid were 63 and 90%, respectively. The limits of detection of the assay for ethyl clofibrate and clofibric acid in human plasma were 1.1 and 1.5 micrograms/ml, respectively. Limits of quantitation of the assay for ethyl clofibrate and clofibric acid in human plasma were 3.6 and 4.9 micrograms/ml, respectively. The HPLC assay was used to monitor the plasma concentration-time profiles of ethyl clofibrate released from polylactic nanocapsules both in man and rat. The simultaneous determination of ethyl clofibrate and clofibric acid provided evidence that these colloidal systems are stable in human plasma whereas they are lysed in rat plasma. PMID- 7866549 TI - High-performance liquid chromatographic assay of human red blood cell thiopurine methyltransferase activity. AB - An assay is described for the determination of red blood cell (RBC) thiopurine methyltransferase (TPMT) activity. TPMT S-methylates the antileukaemic drugs 6 mercaptopurine (6-MP) and 6-thioguanine and enzyme activity is inherited as a genetic trait. The assay is based on the TPMT-catalysed conversion of 6-MP to 6 methylmercaptopurine (methyl-MP) with non-radioactive S-adenosyl-L-methionine as the methyl donor. The methyl-MP metabolite is extracted into toluene as a phenyl mercury adduct and back-extracted into 0.1 M HCl. Methyl-MP is quantitated by reversed-phase high-performance liquid chromatography (HPLC) with ultraviolet detection using a C18 Resolve cartridge and a mobile phase of methanol-water (20:80, v/v) with 100 mM triethylamine adjusted to pH 3.2 with orthophosphoric acid. There was a strong correlation between the HPLC assay and the established radiochemical assay (P < 0.0001). TPMT activities were measured by both methods in a population study of 111 children. There was no significant difference between the two frequency distribution histograms (P > 0.6). PMID- 7866550 TI - Simultaneous determination of urinary creatinine, calcium and other inorganic cations by capillary zone electrophoresis with indirect ultraviolet detection. AB - A method for the rapid analysis of calcium and creatinine in urine has been developed using capillary zone electrophoresis without sample pretreatment other than dilution. Cations of NH3, K, Na, Mg, Ca, Li, Ba and creatinine in human urine samples could be separated within 7 min. Background electrolyte (BGE) was composed of 5 mmol/l pyridine (chromophore), 3.6 mmol/l tartaric acid and 2 mmol/l 18-crown-6, having a pH of 4.05. An indirect UV detection mode was employed at 255 nm. Efforts were made to eliminate the interaction between cations and proteins and to minimize the electromigrative dispersion (EMD) for the analytes of interest by selecting a suitable BGE and sample dilution solution. Quantitative analyses were performed for calcium and creatinine. The calibration plots showed good linearity over the concentration range of interest to clinical analysis. Data on recoveries and reproducibilities are also reported. Results for urine samples (previously collected and frozen) from a variety of healthy and pathological individuals were in good agreement with those obtained by the Technicon SMA II calcium and creatinine methods. PMID- 7866552 TI - Radical-derived oxidation products of 5-aminosalicylic acid and N-acetyl-5 aminosalicylic acid. AB - 5-Aminosalicylic acid is an agent effective in the treatment of chronic inflammatory bowel diseases. Its ability to scavenge radicals is considered to be a major factor responsible for its therapeutic efficacy. In this study oxidation products of aminosalicylates with hydroxyl radicals were produced. The compounds that could be discovered by gas chromatographic-mass spectrometric analysis originate from a 1,4-benzoquinone monoimine intermediate which subsequently undergoes multiple reactions such as hydrolysis, reductive 1,4-Michael addition, reoxidation and decarboxylation. Some of these products could represent metabolites formed under in vivo conditions and thus provide a tool for screening biological material from subjects under different clinical conditions. PMID- 7866551 TI - Fatal poisoning with detajmium: identification of detajmium and its metabolites and artifacts by gas chromatography-mass spectrometry and quantification by high performance liquid chromatography. AB - After ingestion of an unknown dose of detajmium, a 14-year-old female collapsed with asystolia. Resuscitation efforts were not successful. A medicolegal autopsy was carried out, and blood, liver and gastric content were extracted and analyzed by gas chromatography-mass spectrometry (GC-MS). After derivatization with acetic anhydride, detajmium and twelve of its derivatives and metabolites were identified. The main metabolic pathways include hydroxylation and subsequent O methylation of the indol ring, and oxidation as well as reduction of the C-21 hydroxyl function. Cleavage of the N-alkyl side-chain is a further, possibly non enzymatic degradation pathway. Artifact formation induced by acetylation included dehydratation of the hydroxyl function of C-21 and the N-alkyl side-chain. The detajmium concentration in blood of the decreased was determined by high performance liquid chromatography with fluorimetric detection (12 micrograms/ml). PMID- 7866553 TI - Determination of embutramide in biological matrices by gas chromatography with nitrogen-phosphorus detection. AB - Embutramide is a general anesthetic having a strong narcotic effect on the central nervous system where it paralyzes the brain center that controls respiration. It is a constituent of T61, a veterinary euthanasia drug. This paper describes a gas chromatographic procedure using nitrogen-phosphorus detection for the determination of embutramide in biological matrices. The drug and the internal standard (ambucetamide) are extracted with dichloromethane under alkaline conditions. The method is linear from 100 to 3000 ng/ml. The within-day and day-to-day coefficients of variation range from 5.1 to 5.7% and from 9.1 to 10.0%, respectively. The recovery is above 80% while the minimum detectable level under the conditions described is 40 ng/ml analyzing a 1-ml or a 1-g aliquot of a sample (blood or tissue). The method is also applied to different samples from dogs euthanized with T61. PMID- 7866554 TI - Heterogeneity of alpha 1-acid glycoprotein in rheumatoid arthritis. AB - alpha 1-Acid glycoprotein (AGP) or orosomucoid is a major serum glycoprotein, of unknown physiological function, which is classified as one of the positive acute phase reactants since its plasma concentration becomes elevated two- to five-fold in certain disease states. Additionally, the proportions and identities of the five asparaginyl-linked complex oligosaccharide chains are altered during several physiological and pathological conditions, which may be functionally significant. The key to studying the structural heterogeneity of AGP is to develop a procedure that will isolate AGP without structural degradation. We have developed a method for the purification of AGP, using procedures unlikely to damage the glycoprotein structure, which was utilised to isolate AGP from samples of normal and rheumatoid plasma. The effectiveness of the purification procedure was examined by enzymatically deglycosylating each sample of AGP and separating the released oligosaccharides by chromatography on a pellicular high-performance anion exchange (HPAE) resin at pH 13. The analytical profile for normal AGP was consistent with that previously reported thus indicating that the purification procedure did not denature the oligosaccharide chains of AGP. Additionally, there was a noticeable difference between the profiles for AGP from normal and rheumatoid plasma. PMID- 7866555 TI - Comparison of the determination of four sulphonamides and their N4-acetyl metabolites in swine muscle tissue using liquid chromatography with ultraviolet and mass spectral detection. AB - A discharge-assisted LC-MS method has been developed and validated for the analysis of four sulphonamides (sulphathiazole, sulphadiazine, sulphamerazine and sulphadimidine) and their N4-acetyl metabolites in the muscle of swine treated with Polysulpha-Complex, which contains all four drugs. The clean-up procedure developed involved chloroform-acetone extraction followed by Sep-Pak silica solid phase extraction. In parallel a LC-UV method was validated using the same clean up procedure. Blank tissue was fortified at levels between 20 and 100 micrograms/kg. [13C]sulphadimidine was used as internal standard. The samples were analysed with thermospray LC-MS. The [M + H]+ ion was the major ion in all cases and was employed for single-ion monitoring. The limits of detection (LOD) were below 25 micrograms/kg and the limits of quantification (LOQ) for most sulphonamides were ca. 100 micrograms/kg. Incurred muscle tissues were measured by both LC methods and the concentrations of the sulphonamides were found to be similar. However, the LC-MS procedure is more suitable for confirmatory analysis due to its specificity. PMID- 7866556 TI - Application of the desulfurization of phenothiazines for a sensitive detection method by high-performance liquid chromatography. AB - A simple and sensitive high-performance liquid chromatographic (HPLC) method for the determination of phenothiazine (PHE) is described. PHE is converted to diphenylamine (DIP) by desulfurization with Raney nickel catalyst. DIP is highly sensitive to electrochemical detection. The calibration graph for PHE quantification after desulfurization was linear between 0.1 and 2.0 ng per injection. The detection limit (signal-to-noise ratio = 3) of PHE after desulfurization was 10 pg, which is twenty times higher than that of the parent compound PHE. The proposed desulfurization technique was applied to other PHE related compounds. The structural confirmation of the desulfurized product of PHE was carried out by LC-MS using atmospheric pressure chemical ionization. PMID- 7866557 TI - High-performance liquid chromatographic determination of phenylephrine in human serum using column switching with fluorescence detection. AB - A method for the determination of total phenylephrine (free plus conjugated) in human serum was developed using column-switching high-performance liquid chromatography (HPLC) with fluorescence detection. After serum was deproteinized with acetonitrile, the conjugated phenylephrine was hydrolyzed with diluted hydrochloric acid. The solution was evaporated to dryness. The reconstituted residue was analyzed with HPLC using a heart-cut technique. Good recoveries of the analytes from spiked human serum samples were obtained with small coefficients of variation. A good linear response was obtained for the concentration range 5-500 ng/ml. The lower limit of quantitation for phenylephrine in human serum was 5 ng/ml. The method was applied to the determination of phenylephrine in human serum after oral administration of phenylephrine hydrochloride. PMID- 7866558 TI - Finding solutions to support remote area nurses. PMID- 7866559 TI - All things to all people. Interview by Chris Evans. PMID- 7866560 TI - Nursing and the law. A hot January night. PMID- 7866561 TI - Where is the ...? Spot the agency nurse. PMID- 7866562 TI - End of an era in WA nurse education. PMID- 7866563 TI - Salary packaging ... using tinsel to knock out the stuffing. PMID- 7866564 TI - Intractable diseases and bone marrow transplantation. AB - Intractable diseases are defined as diseases of unknown etiopathogenesis, and for which therapeutic strategies remain to be established. They are therefore likely to cause various sequelae. Of the 86 intractable diseases recognized by the Ministry of Health and Welfare of Japan, half are thought to be curable by bone marrow transplantation (BMT). This report shows which diseases are curable by BMT and provides evidence that autoimmune diseases are stem cell disorders. PMID- 7866565 TI - Effect of thyroid-stimulating hormone on cultured thyrocytes obtained from patients with Graves' disease and inhibitive effect by sodium iodide: a functional study. AB - Thyrocytes obtained from patients with Graves' disease were cultured for 3 days. This was followed by culture with 10 mU/mL thyroid stimulating hormone (TSH) (TSH group), TSH and sodium iodide (Nal group), or without (control group) for 3 additional days. On the 8th culture day, the amounts of intra- and extra-cellular cyclic adenosine monophosphate (cAMP), extracellular cAMP and thyroglobulin (TG), peroxidase (PO) activity, and cell numbers were measured. The amounts of intra- and extra-cellular cAMP correlated well. TSH increased the values of cAMP, TG and PO to levels higher than those of the control group. As the amount of Nal added to the medium increased, these values decreased. Addition of 10(-5) mol/L Nal lowered the value of cAMP only. When 10(-4) mol/L Nal was added, these three levels were lower than those of the TSH group and the value of cAMP was almost equal to that of the control group. On cell number, no difference was found between the cells cultured with TSH, TSH and Nal, and without TSH or Nal. When the thyrocytes were cultured with 1 mmol/L dibutyryl cAMP sodium salt or 8 bromoadenosine 3',5'-cyclic monophosphate instead of TSH, 10(-4) mol/L Nal did not lower the values of thyroglobulin and peroxidase activity. These results suggest that the Nal blocks the intracellular signal transduction provoked by TSH, only at the cAMP production level. PMID- 7866566 TI - Photoreceptor differentiation of retinoblastoma: an electron microscopic study of 29 retinoblastomas. AB - Retinoblastomas exhibit a unique form of differentiation to produce cell elements similar to those seen in a photoreceptor cell. An ultrastructural study was performed on 29 cases of retinoblastoma to further clarify the cytologic characteristics of the tumor cells. The age of the retinoblastomas averaged 17.1 months and the tumor cells showing photoreceptor differentiation were demonstrated in 10 cases (35%). The findings were especially notable in retinoblastomas with Flexner-Wintersteiner rosette formation (seven cases, 28%). Similar photoreceptor differentiation was also evident in solid cell clusters without rosette formation (four cases, 14%). The presence of photoreceptor elements was assumed to be significantly frequent both in Flexner-Wintersteiner rosettes and in the solid cell clusters. The cell cytoplasm also showed proliferation of long mitochondria and microtubules, reflecting photoreceptor differentiation. The hereditary-type retinoblastoma showed more advanced cell differentiation than the non-hereditary type. Photoreceptor differentiated retinoblastoma showed rather indolent growth compared with the undifferentiated type, and the former can expect a curative treatment by operation. These observations provide additional findings of the biological nature of retinoblastomas. PMID- 7866567 TI - Antigen expression associated with lymph node metastasis in gastric adenocarcinomas. AB - A total of 100 gastric adenocarcinomas, comprising 50 cases with lymph node metastasis and 50 cases without lymph node metastasis, were examined for immunohistochemical reactivity with the monoclonal antibody to urokinase-type plasminogen activator (u-PA), Lex related 4C9 antigen, Jun, or to nucleobindin (Nuc). In tumors with lymph node metastasis, 41 (82%) were positive for u-PA and 28 (56%) were positive for Nuc. In tumors without lymph node metastasis, 26 (52%) were positive for u-PA and five (10%) were positive for Nuc. The percentage of cases positive for u-PA or Nuc was significantly higher in tumors with lymph node metastasis than that in tumors without lymph node metastasis (P < 0.01). The expression of u-PA was found to be significantly correlated with that of Nuc (P < 0.001), mode of infiltrative growth (P < 0.05), depth of invasion (P < 0.01), and grade of lymphatic invasion (P < 0.01). However, the expression of Nuc was found to be significantly correlated with the expression of Jun (P < 0.05), depth of invasion (P < 0.01), and grade of lymphatic invasion (P < 0.001). These results suggest that immunohistochemical examination for the expression of u-PA and Nuc in tumor cells may help evaluate the potential of adenocarcinomas of the stomach for lymph node metastasis. PMID- 7866568 TI - An autopsy case of acquired immune deficiency syndrome (AIDS) with preceding aplastic anemia. AB - A case of acquired immunodeficiency syndrome (AIDS) with preceding aplastic anemia is reported. The patient was a 36 year old female who had been diagnosed as having aplastic anemia 10 years before and thereafter had received multiple transfusions. Human immunodeficiency virus (HIV)-seropositivity was revealed 10 months prior to her death, but no particular clinical signs indicating HIV infection, pre-AIDS or onset of AIDS were recognized before serological diagnosis, although the slow progression of leukopenia was noted along with thrombocytopenia. Her general condition deteriorated during the last 10 months accompanied by an acute decrease in the CD4/CD8 ratio. Autopsy revealed full blown AIDS: systemic aspergillosis, progressive multifocal leukoencephalopathy, Epstein-Barr virus-related B cell lymphoma arising in the diaphragm and severe lymphocyte depletion in the lymph nodes and spleen. Markedly hypoplastic bone marrow was considered to be primarily attributable to the aplastic anemia but the affection of AIDS was not excluded. The possible transmission route of HIV and the effect of the preceding aplastic anemia on the infection and clinical course of AIDS are discussed. PMID- 7866569 TI - Intracranial chondromyxoid fibroma extending into the jugular foramen. AB - A case is reported of an intracranial chondromyxoid fibroma (CMF) in a 67 year old man. The tumor originated in the petrous part of the temporal bone and extended into the jugular foramen. Microscopically, the tumor showed a lobular appearance, and was composed of spindle or stellate cells in an abundant myxoid, chondroid stroma. Immunohistochemically, S-100 protein was positive in the tumor cells and myxoid stroma. Intracranial CMF, especially in an elderly person, is exceedingly rare. Clinical and pathological findings are presented with reference to the previously reported articles. PMID- 7866571 TI - Malignant peripheral nerve sheath tumor with prominent intracytoplasmic vacuolation: report of a case. AB - A case of malignant peripheral nerve sheath tumor with uncommon features is reported. A mass was noted in the left thigh of a 16 year old man. Histologically, most areas of the tumor exhibited the typical appearance of malignant peripheral nerve sheath tumor, but some tumor cells had rounded nuclei and cytoplasm, resembling an epithelioid pattern. It was noted that some rounded tumor cells showed prominent intracytoplasmic vacuolation. Immunohistochemically, almost all of the tumor cells, including the rounded and vacuolated ones, were positive for S-100 protein and vimentin. Electron microscopic study revealed well developed cytoplasmic processes, intracytoplasmic intermediate-sized filaments, basement lamina formation and extracellular long-spacing collagens. These findings were compatible with those of Schwann cell differentiation. Moreover, ultrastructurally, the vacuolated spaces contained a few granular materials and were derived from the dilatation of the rough endoplasmic reticulum. It is speculated that intracytoplasmic vacuolation in malignant peripheral nerve sheath tumor would be caused by degeneration of the tumor cells. PMID- 7866570 TI - Metastatic pineocytoma of the spinal cord after long-term dormancy. AB - An unusual tumor in the spinal cord of a 57 year old man is reported. At the age of 42 years, the patient had had a pineal region tumor that subsequently disappeared completely after local radiation therapy only. Eleven and 15 years later, at the ages of 53 and 57 years, respectively, solitary spinal cord tumors were found and removed. Pathological examination revealed that these tumors were of neurogenic origin and showed the characteristic features of pineal parenchymal tumors such as pineocytoma and pineoblastoma. Based on the cytology of individual tumor cells and the absence of mitotic figures and necrotic foci, this patient was diagnosed as having metastatic pineocytoma of the spinal cord. This case suggests that distant, subarachnoidal metastasis to the spinal cord can occur in pineocytomas even after long-term dormancy. PMID- 7866572 TI - Invasive ductal carcinoma with a predominant intraductal component arising in a fibroadenoma of the breast. AB - A rare case of invasive ductal carcinoma with a predominant intraductal component arising within a fibroadenoma of the breast in a 42 year old Japanese female was investigated by light microscopy. The patient, who had a well-defined, rubbery breast tumor measuring 2.0 x 3.0 cm, had undergone a tumorectomy 21 months after she noticed the tumor. Histologically, the fundamental architecture of the tumor showed an intracanalicular-type of fibroadenoma, but extensive proliferation of atypical cells was noticed in the lumen of the ducts. Tumor cells in the canaliculi had characteristics of ductal carcinoma, such as solid, comedo and cribriform patterns. As most of the ducts were occupied by carcinoma cells with several foci of microinvasion in the stroma of the fibroadenoma, it was diagnosed as invasive ductal carcinoma with a predominant intraductal component arising within a fibroadenoma. This coexistence of in situ proliferation and invasive lesions of carcinoma within a fibroadenoma suggest the origin of the carcinoma to have been in the epithelial component of the fibroadenoma. In addition, this study clarifies the fact that carcinoma cells may proliferate and spread along the lumen of pre-existing ducts of the fibroadenoma and speculates that the duct system of the fibroadenoma has complete continuity. PMID- 7866574 TI - Neoplasms. PMID- 7866573 TI - Lewy bodies in the cerebellar dentate nucleus of a patient with Parkinson's disease. PMID- 7866575 TI - Trauma and rehabilitation. PMID- 7866576 TI - Metabolic disorders and neurotoxicology. PMID- 7866577 TI - Molecular biology, genetics, and central nervous system neoplasms. Commentary. PMID- 7866578 TI - Molecular genetics of astrocytomas and meningiomas. AB - Although both spatial and temporal heterogeneity confound the description of the genetic events underlying glioma tumorigenesis, it is becoming evident that chromosome 17 loss and p53 inactivating mutations are probably involved early in the pathway of tumorigenesis of some, but not all, astrocytomas. Chromosome 10 loss and epidermal growth factor receptor amplification are seen predominantly in high-grade lesions, although they have not been shown to be independent prognostic indicators. Data is accumulating on the presence of a tumor suppressor gene on chromosome 9p, although the gene remains to be identified. The roles of chromosome 22 and the NF-2 tumor suppressor gene in the tumorigenesis of sporadic and familial meningiomas are discussed here, along with other nonrandom chromosomal alterations that are seen in both astrocytomas and meningiomas. PMID- 7866579 TI - Diagnosis and treatment of pediatric brain tumors. AB - Brain tumors are the most common form of solid neoplasm of childhood. Progress is clearly being made in the understanding and management of childhood brain tumors. There are possible biologic differences between histologically similar childhood and adult brain tumors. Chemotherapy is a major component of the treatment of many forms of childhood primary central nervous system tumors and is being used in attempts to improve survival and to delay or decrease the amount of radiotherapy needed. Despite the use of more aggressive radiotherapy approaches or intensified chemotherapy approaches, the outcome remains dismal for some forms of brain cancer. Many unsettled issues exist concerning the management of childhood low-grade gliomas. PMID- 7866580 TI - New approaches to molecular therapy of brain tumors. AB - Little progress has been made in the treatment outcome of patients with glioblastoma in the past 10 to 15 years, despite an aggressive multimodality regimen using surgery, radiation, and chemotherapy. New approaches, particularly molecular strategies, have become the clinicians' and scientists' hope for the future in brain-tumor therapy. Several molecular approaches have been shown to have in vitro and in vivo activities against brain tumor cells. These include the use of retroviral and adenoviral vectors, herpes simplex viruses, antisense vectors, and antisense oligonucleotides. Preclinical studies with the retroviral vector have already been extended to a clinical trial, clearly demonstrating the clinical potential of these molecular approaches. PMID- 7866581 TI - Neuroscience and neurorehabilitation. PMID- 7866582 TI - Secondary mechanisms in neuronal trauma. AB - Secondary damage in central nervous system trauma results from toxic effects of a variety of modulators that magnify the initial traumatic damage. These modulators include the excitatory transmitter glutamate, the intracellular messenger calcium, and the intercellular messenger nitric oxide. Glutamate-induced toxicity, called excitotoxicity, occurs from excess glutamate release following trauma. Passage of calcium into the cell through a specific postsynaptic glutamate receptor ion channel, the N-methyl-D-aspartate (NMDA) receptor, is crucial in activating cellular pathways leading to excitotoxic damage. The NMDA receptor requires both glutamate and glycine for activation and is blocked by many drugs that act at either of these sites. It is also blocked by agents that selectively block the ion channel of this receptor. Blocking NMDA receptors at any of these sites decreases the cellular damage mediated by glutamate in neuronal trauma and improves physiological measures associated with traumatic damage. Other strategies to limit secondary damage include blockade of other calcium channels, of calcium-activated enzymes, and of processes that mediate the effects of calcium. Calcium-activated enzymes include nitric oxide synthase and phospholipases, which cause production of free radicals. In combination with NMDA receptor blockade, these sites represent promising areas for therapeutic intervention in secondary traumatic damage. PMID- 7866584 TI - Intensive care neurology. AB - Critical care neurology is a rapidly developing subspecialty of neurology. The neuro-intensivist is called upon to manage critically ill patients with stroke, neuromuscular disease, traumatic injury, increased intracranial pressure, and other disorders. Therapeutic and technologic advances are rapidly being incorporated into practice and will improve patient care and outcome. PMID- 7866583 TI - Enhancement of locomotor recovery following spinal cord injury. AB - Recent advances have been made in new experimental approaches to enhance locomotor recovery in spinal cord-injured subjects. Research in adult animals whose spinal cords have been transected (spinal animals) has focused particularly on locomotor recovery and the use of pharmacological tools to trigger and modulate the locomotor pattern. This provides a rational basis for the rehabilitation and pharmacotherapy of locomotion in spinal cord-injured patients. Findings in the field of locomotor training, locomotor pharmacotherapy, and functional electrical stimulation are reviewed. It is argued that a combination of the various approaches will provide an optimal base for functional locomotor recovery. PMID- 7866585 TI - Mitochondrial function and neurotoxicity. AB - There have been important advances in our understanding of the nuclear factors that regulate mitochondrial DNA function. Nuclear involvement in respiratory chain dysfunction is also being investigated, and evidence is accumulating that this may be more important than previously thought. In particular, the cytochrome oxidase deficiency found in senescent tissue may be caused by a nuclear rather than a mitochondrial defect. Studies continue to demonstrate a mitochondrial defect in certain neurodegenerative diseases, although controversy still surrounds the tissue distribution of such deficiencies. The relationship of such deficiencies to pathogenesis remains uncertain. PMID- 7866586 TI - Metabolic disorders in children. AB - This year has seen major progress in gene therapy, particularly that directed to the liver. Genes have been characterized for Wilson's disease, Krabbe's disease, Canavan's disease, adrenoleukodystrophy, glucose-6-phosphatase, and long-chain 3 hydroxyacyl-CoA dehydrogenase. Moreover, the identification of common mutations in many conditions promises to help with diagnosis and genetic counseling. The drama of progress in molecular biology can easily overshadow other research, but the application of tandem mass spectrometry to neonatal screening is a major advance. Other important papers concern the use of Lorenzo's oil in adrenoleukodystrophy and revised dietary recommendations for the treatment of phenylketonuria. This review focuses predominantly on diseases that affect the brain, but important advances in other conditions have been included. PMID- 7866587 TI - Neurochemistry and toxin models in Huntington's disease. AB - Huntington's disease (HD) is a prototypical neurodegenerative disease characterized by selective loss of neurons in the basal ganglia. Although the gene defect has recently been identified, the mechanism by which it leads to neuronal degeneration remains unknown. We have hypothesized that a defect in oxidative phosphorylation may lead to slow, excitotoxic neuronal degeneration in this illness. Evidence for such a defect is reviewed here, including our recent studies using magnetic resonance imaging spectroscopy that show elevated lactate levels in the basal ganglia and cerebral cortex of patients with HD. If a defect in energy metabolism is responsible for neuronal degeneration in HD, it should be possible to mimic the neurodegenerative process with mitochondrial toxins. Our recent studies with 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase, show that it can produce striking similarities to the neuropathologic and neurochemical features of HD in both rodents and primates. If such a mechanism is indeed relevant to the pathogenesis of HD, then agents that can improve oxidative phosphorylation might prove to be efficacious. We found that both coenzyme Q10 and nicotinamide can ameliorate striatal lesions produced by mitochondrial toxins in vivo. Furthermore, they reduced elevated lactate concentrations when administered to patients with HD. This finding raises the possibility that such an approach might prove useful in trying to slow the neurodegenerative process. PMID- 7866588 TI - Metals and free radicals in neurodegeneration. AB - Substantial evidence has accumulated implicating metals and free radicals in the pathogenesis of the major neurodegenerative disorders (Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis). Metal-induced oxidant stress can damage critical biological molecules and initiate a cascade of events including mitochondrial dysfunction, excitotoxicity, and a rise in cytosolic free calcium, leading to cell death. In Parkinson's disease and Alzheimer's disease there is evidence of oxidative stress in affected brain regions, as indicated by increased metal accumulation (which promotes free radical formation), decreased antioxidant levels (which protect against free radical formation), and oxidative damage. Recently, studies of the familial form of amyotrophic lateral sclerosis have detected mutations in the gene that encodes superoxide dismutase, which is one of the body's primary oxidant defense mechanisms. Mice that are transfected with the human mutant superoxide dismutase gene develop an amyotrophic lateral sclerosis syndrome. These studies demonstrate that oxidant stress can initiate the development of a chronic progressive neurodegenerative disorder. PMID- 7866589 TI - The HOT Study: design and cost of major blood pressure trials. PMID- 7866590 TI - Nitric oxide (NO) in the cardiovascular system: role in atherosclerosis and hypercholesterolemia. AB - Atherosclerosis is characterized by hypertrophy of the vascular media, intimal thickening and lipid-containing plaques. Atherosclerosis is a progressive systemic vascular disease which leads to impaired tissue perfusion due to vascular obstruction. In advanced stages it is often complicated by thrombosis. Recent research demonstrates that atherosclerosis is also a functional disease. In atherosclerosis and hypercholesterolemia, normal vasodilatation is impaired due to endothelial dysfunction. In addition, the ability of the vessel wall to reject adhering and aggregating platelets is deteriorated. Endothelial dysfunction in atherosclerosis is characterized by impaired formation of nitric oxide (NO), formerly known as endothelium-derived relaxing factor (EDRF). NO is continuously formed in the vascular endothelium and promotes tissue perfusion by relaxation of vascular smooth muscle. Endogenously formed NO may also protect against foam cell formation and media hypertrophy, i.e. against the structural component of atherosclerosis. In patients with ischaemic heart disease, the endothelial dysfunction leads to decreased ability to dilate the coronary vessels in response to several forms of physiological stimuli. Endothelial dysfunction in atherosclerosis is reversed by lipid-lowering therapeutic interventions. PMID- 7866591 TI - Using Hawksley random zero sphygmomanometer as a gold standard may result in misleading conclusions. AB - We combined a database of paired blood pressure measurements taken using the Hawksley random-zero sphygmonanometer and a standard mercury sphygmomanometer and a database of paired measurements made on a SpaceLabs 90202 ambulatory blood pressure recorder and standard sphygmomanometer to determine how the SpaceLabs 90202 would have fared if it had been assessed against the Hawksley random-zero sphygmomanometer instead of a standard sphygmomanometer. The pooled database contained 255 triplicate readings. Using the standard sphygmomanometer as gold standard, the Spacelabs had a median error of 2 mm/Hg for both systolic and diastolic. Against the Hawksley random-zero sphygmomanometer, median error was -3 mm systolic and -6 mm diastolic. The proportion of errors > 10 mm rose from 11% (systolic) and 9% (diastolic) with the standard sphygmomanometer to 16% and 29% with the Hawksley random-zero sphygmomanometer. Because it underestimates systolic and diastolic pressures, the use of the Hawksley random-zero sphygmomanometer as a gold standard may have resulted in misleading conclusions about performance of some automated BP recorders. PMID- 7866592 TI - Impaired glucose and insulin metabolism in borderline hypertension. AB - This study investigated glucose and insulin metabolism in borderline hypertension (BHT) defined as repeated diastolic blood pressures (DBP) of 85-94 mmHg. Seventy five BHT and 75 age-matched normotensive (NT, DBP < or = 80 mmHg) men were recruited from a population screening programme. Plasma lipoproteins were determined and an oral glucose tolerance test was performed (WHO criteria). Fasting insulin was significantly higher in the BHT group (17.2 vs 14.2 mU/ml, p < 0.001), whereas fasting blood glucose levels were similar in the two groups, indicating a reduced insulin sensitivity. The BHT group had significantly lower levels of HDL cholesterol and higher levels of plasma triglycerides, VLDL cholesterol and VLDL triglycerides. When adjusted for BMI these differences disappeared, whereas the basal insulin levels remained significantly elevated (F = 10.7, p < 0.001). These results indicate that an altered glucose and insulin metabolism is present already in the early stages of hypertension. They also suggest that these disturbances are only partly dependent on BMI. This supports the hypothesis that reduced insulin sensitivity could be of importance in the early phases of essential hypertension. PMID- 7866593 TI - Do autonomic cardiovascular reflexes predict the nocturnal rise in blood pressure in obstructive sleep apnea syndrome? AB - To investigate the relationship between nocturnal changes in blood pressure (BP) and diurnal cardiovascular reflexes we examined a group of 19 male normotensive obstructive sleep apnea syndrome (OSAS) patients. All patients underwent a full polysomnographic examination including BP monitoring by a finger arterial pressure device (Finapres) and a battery of cardiovascular reflex tests; plasma catecholamine levels at rest were also measured. During sleep, BP increased with an average difference of 15.4 +/- 7.5 mmHg for systolic and 8.3 +/- 4.6 mmHg for diastolic pressure. Compared with control subjects, OSAS patients had lower values of Valsalva ratio (VR) (1.75 +/- 0.4 vs 1.34 +/- 0.2, p = 0.0004), E/I ratio (1.35 +/- 0.2 vs 1.13 +/- 0.9, p = 0.0004) and baroreflex sensitivity index (BRSI) (5.4 +/- 2.1 vs 2.7 +/- 1.9 mms/mmg, p = 0.0006) and a higher systolic (p = 0.02) and diastolic (p = 0.002) pressure response to tilting-up test. Noradrenaline plasma levels were also significantly higher (345 +/- 125 vs 224 +/ 92 pg/ml, p = 0.001). No significant correlations were found between the nocturnal rise in BP and the pressure responses during sympathetic manoeuvres or rest levels of noradrenaline. The nocturnal changes in systolic blood pressure during the night were negatively dependent on the diurnal BRSI (r = -0.91, p = 0.0007) and VR (r = -0.70, p = 0.006). We conclude that the high levels of noradrenaline at rest and the altered sympathetic cardiovascular reflexes alone do not account for the nocturnal variation in blood pressure in OSAS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866594 TI - Prediction and optimisation of the antihypertensive response to nifedipine. AB - The predictability of the long term antihypertensive response to nifedipine in individual patients has been assessed by an analysis based upon the concentration effect parameters defined following the first dose administration of 20 mg nifedipine (Retard). The predicted and measured reductions in blood pressure during steady state nifedipine treatment were compared for the trough and peak responses and there was reasonable agreement for the group of patients as a whole. However, when the measured and predicted blood pressure profiles were compared for each individual patient there was close agreement for the majority of patients but there were significant discrepancies in a few cases. Further analysis of the steady state concentrations in these cases revealed that there was no change in their responsiveness to nifedipine and that discrepancies were directly attributable to inappropriate compliance with the drug regimen. The analysis was further extended to simulate the blood pressure responses to alternative fixed dosage regimens. Assessment of these simulations suggests that blood pressure control with nifedipine Retard is significantly improved by three times daily drug administration. PMID- 7866595 TI - Interactions between serotonin and endogenous and exogenous noradrenaline in the human forearm. AB - We investigated the interactions between serotonin (5-hydroxytryptamine, 5-HT) and exogenous or endogenous noradrenaline (NA) in the forearm of normotensive volunteers (n = 24), using venous occlusion plethysmography. Endogenous release of NA was stimulated by lower body negative pressure (LBNP; -10, -20 and -40 mmHg) and by intra-arterial (i.a.) infusions of tyramine (0.1 to 1 microgram/kg/min). Exogenous NA was infused in cumulative doses (0.3 to 10 ng/kg/min). All experiments were performed in the presence of either vehicle (0.4 mL/min), sodium nitroprusside (SNP; 3 or 5 ng/kg/min), or 5-HT (0.1 or 1 ng/kg/min). NA or 5-HT (1 ng/kg/min) were also infused with the selective 5-HT2 receptor antagonist ritanserin (500 ng/kg/min). Angiotensin II (Ang II; 0.03 to 0.3 ng/kg/min) was given as a vasoconstrictor control (n = 6). Vasoconstriction to exogenous NA was significantly enhanced by 5-HT (1 ng/kg/min; p < 0.05) in one group of subjects, but this could not be reproduced in a second group. In contrast, the vasoconstrictor responses to endogenous NA remained unaffected by 5 HT. SNP caused the same degree of vasodilation as 5-HT, and was followed by a similar response to NA. Ritanserin did not alter the vasoconstriction to infused NA, nor vasoconstriction to infused NA when combined with 5-HT. The vasoconstrictor response to Ang II was not influenced by 5-HT (0.1 ng/kg/min). Apparently, a synergistic effect between 5-HT and NA in the periphery involves a nonspecific mechanism. The latter seems to be confined to infused NA. The precise role of the 5-HT2 receptor in this interaction could not be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866596 TI - Cardiac and neurologic complications in malignant hypertension due to oral contraceptive use. AB - Malignant hypertension is a rare consequence of contraceptive use. We report here on two young women with malignant hypertension secondary to contraceptive use whose main symptomatology was neurological. Both patients had renal failure, severe left ventricle hypertrophy, and hemorrhagic stroke, all reversible after control of blood pressure and discontinuation of the contraceptive pill. PMID- 7866597 TI - The Hypertension Optimal Treatment (HOT) Study--patient characteristics: randomization, risk profiles, and early blood pressure results. AB - The Hypertension Optimal Treatment (HOT) Study is a prospective, randomized, multicenter trial being conducted in 26 countries. Its main aim is to evaluate the relationship between three levels of target diastolic blood pressure (< or = 90, < or = 85 or < or = 80 mmHg) and cardiovascular morbidity and mortality in hypertensive patients. In addition, the study will examine the effects on morbidity and mortality of a low dose, 75 mg daily, of acetylsalicylic acid (ASA, aspirin) or placebo. In the HOT Study, basic antihypertensive treatment is initiated with the calcium antagonist felodipine at a dose of 5 mg daily. If target blood pressure is not reached, additional antihypertensive therapy with either an angiotensin converting enzyme (ACE) inhibitor or a beta-adrenoceptor blocking agent is given. Further dosage adjustments are made in accordance with a set protocol. As a fifth and final step, a diuretic may be added. Inclusion of patients was stopped on April 30, 1994. At that time 19,196 patients had been randomized. There were 9,055 (47%) women and 10,141 (53%) men with an average age of 61.5 +/- 7.5 (SD) years. At enrollment, 52% of patients were receiving antihypertensive treatment. These patients entered a wash-out period of at least 2 weeks before randomization. The average randomization blood pressure in untreated patients was 169 +/- 14/106 +/- 3 mmHg and in the treated patients 170 +/- 14/105 +/- 3 mmHg. On August 15, 1994, blood pressure data were available for 14,710 and 10,275 patients, who had completed 3 and 6 months treatment, respectively. The average reduction in diastolic blood pressure was 22 mmHg after 6 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866598 TI - Depressed cheek cell sodium transport in human hypertension. AB - Na+ transport activity was measured in cheek cells from untreated hypertensive subjects and age-matched normotensive controls identified from a blood pressure screening program. Cheek cells were isolated by a simple mouth wash procedure and Na+ transport activity was measured as the proton-dependent uptake of 22Na+ using a rapid filtration assay. The rate of Na+ uptake was about 45% lower in hypertensive subjects and this difference persisted in a follow up study 2 years later involving those subjects who remained untreated for their hypertension. The proton independent Na+ uptake was also reduced by about 46% in the hypertensive group. The increase in the rate of cheek cell Na+ transport with increasing transcellular proton gradient values was also significantly lower in hypertensive subjects. The reduced cheek cell Na+ transport observed in hypertensive subjects may indicate decreased activity of the Na+/H+ antiporter and/or changes in the ion permeability properties of the cheek cell plasma membrane in the hypertensive state. This novel assay provides a biochemically based method for discriminating between normotensive and hypertensive subjects and makes use of tissue which can be obtained in a relatively non-invasive manner. PMID- 7866599 TI - Nutritional status modifies insulin-mediated glucose uptake in spontaneously hypertensive rats. AB - In this study we quantified insulin-mediated glucose uptake in weight-matched (260-330 g) fed (6-8 h fast) and fasted (24 h fast) male rats with spontaneous hypertension (SHR) and control Wistar-Kyoto (WKY) rats. To accomplish this goal, rats were infused continuously for 165 min with glucose and insulin. Blood was taken at frequent intervals from 120-165 min, and the values averaged to determine the steady-state plasma glucose (SSPG) and insulin (SSPI) concentrations. In some studies epinephrine and propranolol were added to the infusate in order to suppress endogenous insulin secretion. Steady-state plasma insulin (SSPI) concentrations were similar in SHR and WKY during the three infusion studies (382-483 pmol/L). However, SSPG was significantly higher in fed SHR as compared to fed WKY during infusions performed with (9.4 +/- 0.8 vs 7.0 +/ 0.4 mmol/L, p < 0.05) or without (8.6 +/- 0.2 vs 7.0 +/- 0.6 mmol/L, p < 0.05) epinephrine and propranolol in the infusate. In contrast, SSPG concentrations (mmol/L) were similar in SHR (6.8 +/- 0.3) and WKY rats (6.5 +/- 0.6) when they were studied after a 24 h fast. These results demonstrates that differences in insulin-mediated glucose removal from plasma between SHR and WKY rats will vary as a function of nutritional status. PMID- 7866600 TI - Increased left ventricular non-uniformity in hypertensive patients with angina. AB - AIM: To determine how hypertension affects the left ventricular diastolic function of patients with effort angina. METHODS: We performed radionuclide ventriculography in 14 patients with isolated stenosis of the left anterior descending coronary artery and in seven healthy volunteers. RESULTS: Neither global nor regional peak filling rate differed significantly between the patients with (n = 6) and without (n = 8) hypertension, although the left ventricular asynchronous index was significantly increased (P < 0.05) in the hypertensive patients (87 +/- 20 ms), compared with the normotensive patients (59 +/- 22 ms). This index was significantly (P < 0.05) correlated with left ventricular mass index in all participants. CONCLUSIONS: Hypertension increased the diastolic non uniformity of the left ventricle in patients with effort angina. PMID- 7866601 TI - Effects of N-nitro-L-arginine on coronary artery tone and reactive hyperemia after brief coronary occlusion in conscious dogs. AB - AIM: To determine the role of an endothelium-derived relaxing factor (nitric oxide) in controlling basal coronary tone and coronary vasomotion after brief coronary occlusion (reactive hyperemia). METHODS: In 10 chronically instrumented conscious dogs, we studied the diameter changes of the large epicardial coronary artery and coronary blood flow in response to intracoronary administration of acetylcholine (0.1 and 1 microgram) and brief coronary occlusion for 5 and 20 s before and after intracoronary infusion of N-nitro-L-arginine (LNNA). RESULTS: Intracoronary infusion of LNNA (1, 3, and 10 mg) decreased the diameter of the large epicardial coronary artery and coronary blood flow in a dose-dependent manner without altering arterial pressure and heart rate. LNNA (10 mg) significantly attenuated the increase in artery diameter and coronary blood flow by acetylcholine. The ratio of artery dilation to the blood flow response after acetylcholine was not affected by LNNA. LNNA (10 mg) significantly decreased the ratio of repayment to debt flow volume of reactive hyperemia, but did not affect the ratio of peak to resting flow; it also significantly attenuated the reactive dilation of the large epicardial coronary artery after reactive hyperemia. The ratio of artery dilation to repayment flow volume (micron/ml) during reactive hyperemia was attenuated significantly by LNNA. CONCLUSION: These findings suggest that endothelium-derived nitric oxide may contribute to basal coronary tone and that reactive dilation of the large epicardial coronary artery during reactive hyperemia was caused by flow-mediated nitric oxide release, whereas coronary artery dilation after acetylcholine was caused largely by the direct receptor-mediated release of nitric oxide. PMID- 7866602 TI - Effects of vasoactive drugs on postoperative coronary bypass flow: a new technique. AB - OBJECTIVE: This study aimed to investigate the influence of vasoactive drugs, including a calcium channel blocker, nitroglycerine, and a beta-blocker, often used after coronary artery bypass grafting (CABG). Measurements were taken using a new, completely implantable, mini-Doppler system. The probes were implanted during CABG, led outside through the thoracic wall, and removed 3 days after the operation by a simple pull. RESULTS: The mean Doppler flow increased dramatically in the calcium channel blocker and the nitroglycerine groups (P = 0.002) and decreased slightly in the beta-blocker group (P = 0.015). Mean arterial pressure decreased significantly in all three groups. Heart rate decreased in the beta blocker group (P = 0.002). Changes in the other hemodynamic variables measured were not significant; there were no changes in the control group. Doppler sonographic monitoring of bypass diameters did not show any changes. CONCLUSION: This is the first study to measure the influence of vasoactive drugs directly and online after CABG. From our experience of more than 40 implantations, we conclude that our method is easy to use and reliable and will help improve the therapeutic regimen for patients after CABG. PMID- 7866603 TI - Discordance of anti-ischemic and hemodynamic effects of captopril in stable coronary artery disease. AB - BACKGROUND: The role of angiotensin converting enzyme (ACE) inhibition in patients with coronary artery disease without concomitant disease such as heart failure or hypertension has not been elucidated. In this double-blind, cross over, randomized trial of the ACE inhibitor captopril, its antianginal and anti ischemic effects were studied during monotherapy and in the presence of an organic nitrate. METHODS: Thirty-seven patients (34 men, three women) with stable coronary artery disease and exercise-induced ST-segment depression were enrolled. After a washout phase without medication they received placebo, isosorbide dinitrate (ISDN) 20 mg twice daily, captopril 12.5 mg twice daily, and the combination of both for 1 week each, after which exercise tolerance, blood pressure and heart rate (supine, standing and 24 h profile), and peripheral arterial vasodilatation (finger pulse plethysmography) were assessed. RESULTS: Thirty-three patients completed all phases of the study. Exercise-induced anginal symptoms occurred in 17 patients, and asymptomatic ischemia was seen in the other 16 men. In comparison with ISDN, the anti-ischemic effects of captopril were minimal, despite a similar reduction in blood pressure. Compared with baseline, 1 week of placebo reduced the sum of ST-segment depression, the main efficacy parameter, by 10% (NS), captopril by 19% (NS), ISDN by 37% (P < 0.001) and the combination of captopril and ISDN by 42% (P < 0.001; NS versus ISDN). No patient remained completely free of exercise-induced angina during treatment with captopril; however, three patients after ISDN and seven patients after the combination did (P < 0.05). Blood pressure at rest decreased at peak effect by 9 10% systolic (P < 0.001) with monotherapy and by up to 7% diastolic (P < 0.001), and during combined therapy with captopril and ISDN by 18% systolic (P < 0.001) and 12% diastolic (P < 0.001). Significantly enhanced circulatory effects of captopril plus ISDN versus ISDN were found for blood pressure (P < 0.001) and peripheral arterial vasodilation (P < 0.01). The reflex tachycardia induced by ISDN in the upright position (5 beats/min) was not blocked by captopril during combined therapy. CONCLUSIONS: The antianginal and anti-ischemic effects of captopril alone were marginal, despite significant circulatory effects after short-term administration. Although captopril in combination with ISDN resulted in a significant further blood-pressure-lowering effect and increased peripheral arterial vasodilatation, the magnitude of potentiation of the anti-ischemic nitrate effects was, in contrast, small. Only exercise-induced angina was further improved by the use of the combination. No paradoxical worsening of ischemia or angina was seen after captopril. Thus, although captopril has no place as first line therapy for ischemia, its use in combination with ISDN could be advantageous for long-term prognosis. PMID- 7866604 TI - Safety aspects of spinal cord stimulation in severe angina pectoris. AB - BACKGROUND: Spinal cord stimulation has been used over the past decade for the treatment of patients suffering from intractable angina pectoris, despite having received optimal medical therapy, and who are unsuitable for further surgical intervention. The clinical results are promising and several studies have shown that the antianginal effect of the treatment is associated with a reduction in myocardial ischemia. It has been suggested, however, that spinal cord stimulation may only attenuate the transmission of pain from the heart, without influencing myocardial ischemia. This is a major safety concern when applying this treatment strategy. METHODS: The aim of this study was to assess the potentially unfavourable aspects of spinal cord stimulation in patients with severe coronary artery disease and angina pectoris by means of repeated long-term ECG recordings. Nineteen patients who had been accepted for implantation of spinal cord stimulators for the treatment of severe angina pectoris were included. RESULTS: No increases were noted in the frequency of ischemic episodes, the total ischemic burden, or the number of arrhythmic episodes during treatment. CONCLUSION: The results of this study do not indicate any unfavourable effects of spinal cord stimulation in severe angina pectoris in terms of an increase in the frequency or severity of myocardial ischemia during treatment with spinal cord stimulation. PMID- 7866605 TI - Aluminium phthalocyanines-induced photolysis of human vascular wall cells in culture and the effect of fluoride on photodynamic action. AB - BACKGROUND: Phthalocyanines, second-generation photosensitizers with several attractive properties for use in photodynamic therapy, have been shown to accumulate in malignant lesions and atherosclerotic plaques. After exposure of phthalocyanines-loaded tissues to visible light, the targeted cells become injured and eventually die. In vitro, when fluoride is added before exposure to the light, it can protect some cell types against photodynamic action sensitized by chloroaluminium phthalocyanine (AIPc) and its derivatives. METHODS: The effect of 50 mumol/l chloroaluminium phthalocyanine tetrasulfonate (AIPcS4) and 5 mumol/l AIPc, with and without the addition of 5 mumol/l NaF, on the viability of cultured human endothelial cells (HuEC), human smooth muscle cells (HuSMC), and skin fibroblasts (HuSF) was examined. A 150 W quartz halogen light bulb equipped with a cut-off filter (lambda > 605 nm) was used to activate the phthalocyanines. Cell viability was examined 24 h after irradiation by staining of the cells with fluorescein diacetate/ethidiumbromide and by counting the number of attached cells with a cell counter. RESULTS: In the case of AIPc, the viability of all cell types tested was reduced, in a dose-dependent manner, to about 50% of that of the corresponding controls for a maximum irradiation time of 600 s. When we used AIPcS4, both HuEC and HuSF were considerably less sensitive than HuSMC. The addition of fluoride to AIPc-loaded cells before exposure to light protected HuEC and HuSF, but not HuSMC. In the case of AIPcS4, with and without fluoride, only HuSMC were sensitive. CONCLUSIONS: The addition of fluoride to AIPc or the use of AIPcS4 without fluoride could be a valuable approach, selectively destroying HuSMC without affecting HuEC and HuSF, for the reduction of restenosis rates after recanalization of stenosed or occluded arteries. Moreover, because neither type of phthalocyanines causes cutaneous phototoxicity, these second-generation photosensitizers seem to be best suited to the photodynamic treatment of atherosclerosis. PMID- 7866606 TI - Risk of subsequent cardiac events in stable convalescing patients after first non Q-wave and Q-wave myocardial infarction: the limited role of non-invasive testing. AB - BACKGROUND: Patients recovering from myocardial infarction are frequently evaluated by non-invasive tests for evidence of myocardial ischemia before returning to work or full activity. The purpose of this study was to evaluate the prognostic significance of clinical and non-invasive ischemic test variables assessed in 549 stable, convalescing patients (median 2 months) after their first Q-wave (n = 363) and non-Q-wave (n = 186) myocardial infarction. METHODS: The ischemic tests performed were resting ECG, exercise ECG, ambulatory ECG, and stress thallium scintigraphy. RESULTS: Cardiac events (unstable angina requiring hospitalization, non-fatal reinfarction, or death from cardiac causes) were observed during a mean 23-month follow-up in 57 patients (15.7%) with Q-wave and in 31 of patients (16.7%) with non-Q-wave infarction. In a step-wise Cox regression model, the only significant independent predictors of subsequent cardiac events (P < 0.001) were post-infarction angina and insulin-dependent diabetes mellitus. The type of infarction did not make a significant contribution to the risk of cardiac events (P = 0.29). However, an interaction between infarct type and post-infarction angina was of borderline significance (P = 0.065), with angina associated with more cardiac events in patients with non-Q-wave than in those with Q-wave infarction. None of the ischemic tests contributed significantly to the Cox model in predicting cardiac events in either infarct type. CONCLUSION: Stable convalescing patients who have recovered from first Q wave and non-Q-wave myocardial infarction have similar long-term prognoses. The occurrence of post-infarction angina is associated with increased risk of cardiac events in patients with both infarct types, with more marked effect in non-Q-wave than Q-wave infarctions. Ischemia detected by non-invasive tests performed in the convalescing phase after myocardial infarction was not prognostically useful in either infarct type. PMID- 7866608 TI - Current concepts of the molecular basis of heart failure. PMID- 7866607 TI - Concentration time courses of troponin and myosin subunits after acute myocardial infarction. AB - BACKGROUND: As a result of the limited sensitivity and specificity of creatine kinase and lactate dehydrogenase (LDH) as well as their isoenzymes, there is increasing interest in the use of cardiac contractile proteins for the diagnosis of acute myocardial infarction (AMI) and myocardial damage. METHODS: This study compared the release of creatine kinase, creatine kinase MB, myoglobin, cardiac troponin I (cTnI), cardiac troponin T (cTnT), cardiac myosin light chain-1 (cMLC 1), and beta-type myosin heavy chains (bMHC) in serial blood samples from 13 patients (10 men, three women; median age 54 years, range 40-74 years) with first time AMI (11 Q-wave, two non-Q-wave AMI; three anterior and 10 inferior wall AMI). All but one patient received intravenous thrombolytic treatment. RESULTS: Myoglobin was the first marker to increase in blood after AMI and showed the earliest peak levels, whereas bMHC increased latest, showing the latest peak levels. cTnI and cTnT increased significantly earlier than cMLC-1 and bMHC. cTnI and cTnT increased and reached peak levels parallel to each other, but the latter tended to stay increased longer. cTnT time courses were biphasic in the majority of AMI patients, unlike cTnI time courses. cMLC-1 release was mostly biphasic. cMLC-1 allows diagnosis during the acute phase as well as several days after the onset of AMI. The time courses of bMHC were usually monophasic. Its delayed appearance makes it useful for the diagnosis of remote infarction. In contrast to cTnI and cTnT, cMLC-1 and bMHC time courses were not significantly influenced by early reperfusion. CONCLUSION: Our results demonstrate the impact of the intracellular compartmentation of an intramyocardial protein (cytosolic, structurally bound, or structurally bound with soluble pool) on its concentration time course after AMI, particularly on the rapidity of its release. PMID- 7866609 TI - Bibliography of the current world literature. PMID- 7866610 TI - Common bile duct exploration: the place of laparoscopic choledochotomy. AB - Since laparoscopic cholecystectomy was introduced, the treatment of choledocholithiasis has been modified. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) has been performed selectively in elderly patients and in those with a strong suspicion of biliary duct stones (jaundice, demonstrated at ultrasound). Intraoperative discovery of common duct stones at cystic duct cholangiography signifies that they must be removed intraoperatively [or postoperatively by ERPC and endoscopic sphincterotomy (ES)]. As ES has a failure rate of 3-23%, laparoscopic common duct exploration emerges as the treatment of choice. Since November 1990, we have performed 59 laparoscopic common bile duct explorations. In our experience, the transcystic technique (18 patients) with choledochoscopy appears easier to perform than with fluoroscopy without choledochoscopy. Since, during our early experience, we encountered some difficulty with the transcystic technique, we elected to evaluate common duct exploration through a choledochotomy (41 patients). The main advantage of this technique is that it provides complete access to the ductal system without damage to the papilla. This procedure seems more difficult to perform than the transcystic technique and can be used when there are contraindications to the latter. PMID- 7866611 TI - Laparoscopic inguinal hernia repair with the flared patch. AB - A method is described of using a "flared patch" of woven polypropylene mesh (Marlex or Prolene) to laparoscopically repair inguinal hernial defects. The technique has been used in > 150 patients with indirect (60%) and direct (25%) inguinal hernias. Operating time was reduced from 45 min when the hernial sac was dissected to 25 min using the current technique. All procedures were performed in the outpatient department or during 23-h hospital observation. In the short-term follow-up time of a mean of 12 months (range, 4-23), there has been a 0.67% recurrence rate. The advantages of the laparoscopic approach, which places the operator at the site of the defect, are emphasized by the simplicity of this method. The specific patient benefits include less pain and an earlier return to normal activity, including work. It also allows for the repair of some bilateral hernias. PMID- 7866612 TI - Laparoscopic repair of cholecystoduodenal fistulae. AB - Since the first laparoscopic cholecystectomy in 1987 by Mouret, the scope of biliary surgery available to a laparoscopic surgeon has increased. In the early days of the procedure there were several accepted contraindications. Some of these were acute cholecystitis, morbid obesity, adherent gallbladder, jaundiced patients, ductal calculi, and biliary tract anomalies. In a series of 300 laparoscopic cholecystectomies we encountered five cholecystoduodenal fistulae. It was possible to deal with four fistulae laparoscopically. Two patients underwent a laparotomy, one for a failed laparoscopic repair of cholecystoduodenal fistula and the other for several common bile duct (CBD) stones, which could not be removed laparoscopically via the cystic duct. We maintain that with increasing expertise and improved instrumentation, most cases of cholecystoduodenal fistula could be dealt with laparoscopically. PMID- 7866613 TI - A new technique for closing abdominal fascial openings after laparoscopic surgery. PMID- 7866614 TI - Laparoscopic access to the lesser sac in gastric cancer staging. AB - A new technique to access the lesser sac in gastric cancer staging by laparoscopy is described. The posterior surface of the stomach is approached through the gastrocolic ligament after lifting the stomach by means of a transparietal suture. PMID- 7866615 TI - Laparoscopic surgery in a mobile army surgical hospital deployed to the former Yugoslavia. AB - The 212th Mobile Army Surgical Hospital was deployed from a United States military base in Germany to the former Yugoslavia to provide medical support for more than 25,000 United Nations soldiers. This medical unit was the first mobile hospital ever to deploy with a capability for laparoscopic surgery. During a 2 month trial period, seven laparoscopic procedures were performed for various abdominal emergencies. There were no complications, and all patients returned to full duty within 1 week. No equipment problems or other logistical obstacles were identified. This preliminary report suggests that laparoscopic surgery is quite feasible in a forward-deployed field hospital, allowing combat soldiers to return to full duty in a much shorter time than after conventional surgery. PMID- 7866616 TI - Delayed peritoneal-cutaneous sinus from unretrieved gallstones. AB - We describe a case of spontaneous delayed peritoneal-cutaneous sinus formation from unretrieved gallstones during laparoscopic cholecystectomy. Complete healing required excision of the sinus tract and evacuation of intraperitoneal stones. PMID- 7866617 TI - Traction injury to the liver during laparoscopic cholecystectomy. AB - We describe an intraoperative complication of laparoscopic cholecystectomy and make recommendations to avoid its occurrence. We describe a case in which the liver was lacerated during a routine laparoscopic cholecystectomy. The laceration occurred when the gallbladder was retracted into the suprahepatic space, causing a traction injury of the quadrate lobe, 2 cm lateral to the falciform ligament. The placement of the epigastric trocar through the falciform ligament fixed the liver to the abdominal wall, facilitating the injury. When placing the epigastric trocar, care should be taken to avoid placement through the falciform ligament. If this is not possible, retraction of the gallbladder into the suprahepatic space should be accomplished while observing the liver edge. If the liver edge seems to be under tension, division of the falciform ligament to allow for easy retraction of the liver is recommended. PMID- 7866618 TI - Laparoscopic bilateral truncal vagotomy, antrectomy, and Billroth I anastomosis for prepyloric ulcer. AB - We present a case report of a 48-year-old woman with intractable prepyloric ulcers treated with laparoscopic bilateral truncal vagotomy, antrectomy, and Billroth I anastomosis. The patient was discharged from the hospital on the 5th postoperative day, eating a regular diet. Her postoperative recovery has been uneventful and without complications. Laparoscopic bilateral truncal vagotomy, antrectomy, and Billroth I may be the procedure of choice for intractable prepyloric and pyloric ulcers. PMID- 7866619 TI - Laparoscopic vasectomy. AB - A case is presented in which a laparoscopic vasectomy was performed concomitantly with laparoscopic hernia repair. A laparoscopic vasectomy should not replace an office procedure done under local anesthesia and minimal complications. Reanastomosis after laparoscopic vasectomy is a more complicated procedure. The additional benefit of laparoscopic surgery to those men who desire infertility while having elective pelvic laparoscopic procedures is presented. PMID- 7866620 TI - Laparoscopic gastrostomy: a simple way to feed. AB - A simple two-puncture method of performing laparoscopic gastrostomy under local anesthetic and sedation is described. The advantages are direct visualization at all times and the safe and rapid insertion of a large-bore tube with minimal discomfort to the patient. No special equipment is required except a basic laparoscopic set. PMID- 7866621 TI - Hernia '93: Advances or Controversies--An International Perspective. Indianapolis, Indiana, May 24-27, 1993. Abstracts. PMID- 7866622 TI - Classification of genetic sequences with backpropagation. AB - A backpropagation algorithm is used to train a neural net with the goal of distinguishing between two groups of biological species: prokaryotic and eukaryotic, based on frequencies of all 16 doublets in DNA sequences. An improvement of about 15% is obtained compared to statistical analysis based on one doublet only. This is done first by presenting sequences of species to the network with known classification (the training phase) and then showing species which the neural net has never seen before, and looking for the response. A brief discussion of the speed of training is given. PMID- 7866623 TI - Supervised training of dynamical neural networks for associative memory design and identification of nonlinear maps. AB - Complexity of implementation has been a major difficulty in the development of gradient descent learning algorithms for dynamical neural networks with feedback and recurrent connections. Some insights from the stability properties of the equilibrium points of the network, which suggest an appropriate tailoring of the sigmoidal nonlinear functions, can however be utilized in obtaining simplified learning rules, as demonstrated in this paper. An analytical proof of convergence of the learning scheme under specific conditions is given and some upper bounds on the adaptation parameters for an efficient implementation of the training procedure are developed. The performance features of the learning algorithm are illustrated by applying it to two problems of importance, viz., design of associative memories and nonlinear input-output mapping. For the first application, a systematic procedure is given for training a network to store multiple memory vectors as its stable equilibrium points, whereas for the second application, specific training rules are developed for a three-layer network architecture comprising a dynamical hidden layer for the identification of nonlinear input-output maps. A comparison with the performance of a standard backpropagation network provides an illustration of the capabilities of the present network architecture and the learning algorithm. PMID- 7866624 TI - Generation of associative processes in a neural network with realistic features of architecture and units. AB - A recent neural network model of cortical associative memory incorporating neuronal adaptation by a simplified description of its underlying ionic mechanisms is extended towards more realistic network units and architecture. Excitatory units correspond to groups of adapting pyramidal neurons and inhibitory units to groups of nonadapting interneurons. The network architecture is formed from pairs of one pyramidal and one interneuron unit each with inhibitory connections within and excitatory connections between pairs. The degree of adaptability of the pyramidal units controls the character of the network dynamics. An intermediate adaptability generates limit cycles of transitions between stored patterns and regulates oscillation frequencies in the range of theta rhythms observed in the brain. In particular, neuronal adaptation can impose a direction of transitions between overlapping patterns also in a symmetrically connected network. The model permits a detailed analysis of the transition mechanisms. Temporal sequences of patterns thus formed may constitute parts of associative processes, such as recall of stored sequences or search of pattern subspaces. As a special case, neuronal adaptation can accomplish pattern segmentation by which overlapping patterns are temporally resolved. The type of limit cycles produced by neuronal adaptation may also be of significance for central pattern generators, also for networks involving motor neurons. The applied learning rule of Hebbian type is compared to a modified version also common in neural network modelling. It is also shown that the dependence of the network dynamic behaviour on neuronal adaptability, from fixed point attractors at weak adaptability towards more complex dynamics of limit cycles and chaos at strong adaptability, agrees with that recently observed in a more abstract version of the model. The present description of neuronal adaptation is compared to models based on dynamic firing thresholds. PMID- 7866625 TI - Neural network for control of rearrangeable Clos networks. AB - Rapid evolution in the field of communication networks requires high speed switching technologies. This involves a high degree of parallelism in switching control and routing performed at the hardware level. The multistage crossbar networks have always been attractive to switch designers. In this paper a neural network approach to controlling a three-stage Clos network in real time is proposed. This controller provides optimal routing of communication traffic requests on a call-by-call basis by rearranging existing connections, with a minimum length of rearrangement sequence so that a new blocked call request can be accommodated. The proposed neural network controller uses Paull's rearrangement algorithm, along with the special (least used) switch selection rule in order to minimize the length of rearrangement sequences. The functional behavior of our model is verified by simulations and it is shown that the convergence time required for finding an optimal solution is constant, regardless of the switching network size. The performance is evaluated for random traffic with various traffic loads. Simulation results show that applying the least used switch selection rule increases the efficiency in switch rearrangements, reducing the network convergence time. The implementation aspects are also discussed to show the feasibility of the proposed approach. PMID- 7866626 TI - Multi-expert and hybrid connectionist approach for pattern recognition: speaker identification task. AB - This paper presents and evaluates a modular/hybrid connectionist system for speaker identification. Modularity has emerged as a powerful technique for reducing the complexity of connectionist systems, allowing a priori knowledge to be incorporated into their design. In problems where training data are scarce, such modular systems are likely to generalize significantly better than a monolithic connectionist system. In addition, modules are not restricted to be connectionist: hybrid systems, with e.g. Hidden Markov Models (HMMs), can be designed, combining the advantages of connectionist and non-connectionist approaches. Text independent speaker identification is an inherently complex task where the amount of training data is often limited. It thus provides an ideal domain to test the validity of the modular/hybrid connectionist approach. An architecture is developed in this paper which achieves this identification, based upon the cooperation of several connectionist modules, together with an HMM module. When tested on a population of 102 speakers extracted from the DARPA TIMIT database, perfect identification was obtained. Overall, our recognition results are among the best for any text-independent speaker identification system handling this population size. In a specific comparison with a system based on multivariate auto-regressive models, the modular/hybrid connectionist approach was found to be significantly better in terms of both accuracy and speed. Our design also allows for easy incorporation of new speakers. PMID- 7866627 TI - Storage capacity bounds in multilayer neural networks. AB - General analytic expressions are given for the lower and upper storage capacity bounds of multilayer neural networks which have variable weights between input layer and first hidden layer, and a fixed output function implemented between first hidden and output layer. The special cases of committee and parity machines as well as the limiting cases of networks with minimum and maximum storage capacities are discussed. The results are compared with replica calculations and simulations. An explanation is given as to why the latter have a storage capacity just slightly above the lower limit and how this can be improved. PMID- 7866628 TI - Constrained Potts mean field systems and their electronic implementation. AB - The Potts mean field approach for solving combinatorial optimization problems subject to winner-takes-all constraints is extended for problems subject to additional constraints. Extra variables corresponding to the Lagrange multipliers are incorporated into the Potts formulation for the additional constraints to be satisfied. The extended Potts equations are solved by using constrained gradient descent differential systems. This gradient system is proven theoretically to always produce a legal local optimum solution of the constrained combinatorial optimization problems. An analog electronic circuit implementing the present method is designed on the basis of the previous Potts electronic circuit. The performance of the present method is theoretically evaluated for the constrained maximum cut problems. The lower bound of the cut size obtained with the present method is proven to be the same as that of the basic Potts scheme for the unconstrained maximum cut problems. PMID- 7866629 TI - Dynamical and complexity results for high order neural networks. AB - We present dynamical results concerning neural networks with high order arguments. More precisely, we study the family of block-sequential iteration of neural networks with polynomial arguments. In this context, we prove that, under a symmetric hypothesis, the sequential iteration is the only one of this family to converge to fixed points. The other iteration modes present a highly complex dynamical behavior: non-bounded cycles and simulation of arbitrary non-symmetric linear neural network. We also study a high order memory iteration scheme which accepts an energy functional and bounded cycles in the size of the memory steps. PMID- 7866630 TI - Response classification in psychological testing using a neural network. AB - A feedforward neural network with error backpropagation has been designed to recognize hand-drawn patterns in a cognitive test. The architecture uses both position and direction sensitivity in the input layer. The training set consisted of 659 icons which were shifted horizontally and vertically to give a total training set of 5931 icons. In testing on an independent set of 31,192 icons produced by 557 subjects from a Danish standard population sample, the rate of misclassification was 0.12% compared with an average rate of sequence errors of 1.6%. PMID- 7866631 TI - Proficiency testing in diagnostic molecular pathology. PMID- 7866632 TI - Fishing for chromosomes. The art and its applications. PMID- 7866633 TI - Prognostic significance of p53 immunoreactivity in adult patients with supratentorial fibrillary astrocytic neoplasms. AB - The prognostic significance of p53 immunoreactivity in adult patients with supratentorial fibrillary astrocytic neoplasms was examined by Kaplan-Meier survival analysis. Using a monoclonal antibody that reacts with both mutant and wild-type p53 protein (PAb 1801), reactivity was assessed immunohistochemically in specimens from the first diagnosis of astrocytic neoplasm in 95 patients: 26 astrocytomas (A), 19 anaplastic astrocytomas (AA), and 50 glioblastomas multiforme (GBM). Overall, 53% of cases exhibited any p53 nuclear immunoreactivity, with approximately the same proportion in each histologic grade. Survival was measured from diagnosis to death or last follow-up and ranged from 3 months to 9 years. Histologic grade was a powerful prognostic variable for this group of patients (p < 0.001), with median survivals of 88, 18, and 9 months for A, AA, and GBM patients, respectively. In contrast, patients with p53 immunoreactive or -nonimmunoreactive neoplasms had median survival times of 18 or 15 months, respectively (p = 0.21). These results indicate that p53 immunoreactivity was not prognostically significant in this group of adult patients with supratentorial fibrillary astrocytic neoplasms, although a small difference in survival cannot be excluded. PMID- 7866634 TI - Evaluation of gene deletions by quantitative polymerase chain reaction. Experience with the alpha-thalassemia model. AB - In order to evaluate the feasibility of using quantitative polymerase chain reaction (PCR) to evaluate gene dosage, we developed an assay to detect alpha globin genes, which are frequently deleted in alpha-thalassemia patients. In this quantitative assay alpha-1 and alpha-2 globin consensus regions are coamplified by one oligonucleotide pair, along with a second primer pair targeting a single copy reference gene, namely, tumor necrosis factor alpha, or TNF-alpha. A series of DNA samples titrating alpha-globin against TNF-alpha DNA have a strong linear relationship between template ratios and product ratios (r > 0.98). Minimal sequence divergence (91% homology) between alpha-1 and alpha-2, internal to the identical primer annealing sites, results in a lower amplification efficiency for alpha-1, to 94% of alpha-2 for each cycle. Furthermore, when applied to a variety of individual DNA samples, the signal ratios of alpha-globin to TNF-alpha were far more variable than previously observed for titrated control DNA. We conclude that DNA isolates from different individuals may have idiosyncratic changes in amplification efficiency owing to polymorphic sequence variation and/or variable presence of unidentified contaminants. Despite these potentially confounding factors, however, we were able to identify by quantitative PCR a single gene deletion later confirmed by Southern blot analysis in 20 individual DNA samples. PMID- 7866635 TI - Differential polymerase chain reaction assay of cyclin D1 gene amplification in esophageal carcinoma. AB - The cyclin D1 gene, located on chromosome 11q13, is frequently rearranged in parathyroid neoplasms and amplified in some carcinomas of other organs. Recent studies have detected amplification of cyclin D1 and other markers on chromosome 11q13 (evaluated by Southern or slot blot assays) in approximately 25-50% of squamous cell carcinomas of the esophagus and noted that amplification was associated with lessened survival time. We applied the technique of differential polymerase chain reaction to the evaluation of cyclin D1 gene amplification in squamous cell carcinomas of the esophagus. Cyclin D1 was found to be amplified in 10 of 45 (22%) primary tumors and three of 12 (25%) lymph node metastases. Lymph node metastases tended to be more common in patients with cyclin D1 amplification (70%) than in those without amplification (37%). In 36 patients with follow-up, cyclin D1 amplification was associated with decreased 1 year survival (28% vs. 59%). Cyclin D1 gene amplification in esophageal carcinomas can be evaluated by differential polymerase chain reaction and may provide useful prognostic information. PMID- 7866636 TI - Rapid detection of mycobacterial DNA in clinical samples by multiplex PCR. AB - Triplex-polymerase chain reaction technique (PCR) was developed for the detection and identification of mycobacterial DNA sequences in uncultured clinical samples. A 123 bp fragment corresponding to a specific Mycobacterium tuberculosis sequence complex, a 383 bp DNA fragment encoding for part of the 65 kD mycobacterial surface antigen, and a 268 bp fragment of the human beta-globin gene to demonstrate the presence of suitable DNA were amplified by triplex PCR. To demonstrate the applicability of this method, 206 alcohol-fixed, paraffin embedded sputum samples from 47 patients with culture-proven tuberculosis were investigated. Of 206 samples, 157 were PCR positive, resulting in correct diagnosis of tuberculosis in 46 of 47 (97.8%) patients. Furthermore, 165 alcohol fixed, auramin-stained sputum smears were examined in a blind trial. Triplex PCR revealed tuberculosis in 20 of 21 samples from patients with tuberculosis. In comparison, cultures were positive in 20 of 21 samples, and acid-fast organisms were found by microscopy in 18 of 21 samples. We conclude that triplex PCR is a rapid and sensitive technique for the detection of mycobacterial DNA in uncultured clinical samples and offers equivalent sensitivity (95.2%) and specificity (98.6%) as do culture methods. PMID- 7866637 TI - Loss of heterozygosity and overexpression of p53 gene in human primary prostatic adenocarcinoma. AB - We have examined the loss of heterozygosity (LOH) of codon 72 and evaluated the overexpression of the tumor suppressor gene p53 in 43 primary human prostatic adenocarcinomas (PC). DNA from tumors and normal tissues were extracted from radical prostatectomy specimens. LOH was determined by restriction fragment length polymorphism analysis (RFLP) of the codon-specific endonuclease-digested polymerase chain reaction (PCR) products. Results showed 17 heterozygous cases (39%) among this patient group. Seven of the heterozygous cases displayed LOH. Six of the seven LOH cases were high-grade PCs with Gleason's combined score of > or = 7 and showed capsular invasion. One of the LOH cases, however, displayed an intermediate morphological score of 6 but also with evidence of capsular invasion. The 43 primary PCs were also examined for overexpression of p53 by a monoclonal antibody-mediated immunofluorescence reaction. Overexpression of nuclear p53 as detected by antibody was demonstrable only in tumors with combined morphological Grade > or = 7. No significant overexpression of p53 was noted in lower-grade tumors. In addition, 10 cases of benign prostatic hyperplasia (BPH) were evaluated for p53 expression. All 10 cases showed no detectable p53 overexpression. PMID- 7866638 TI - Inclusion of a sensitivity control to add a quality-control parameter and improve reproducibility in BCR, immunoglobulin, and T-cell receptor gene-rearrangement studies. AB - Molecular analyses to determine clonality of T and B cells in malignant lymphoma and leukemia and to detect the (9;22) translocation in chronic myelogenous leukemia are commonly used in clinical molecular biology laboratories. We describe the inclusion of a sensitivity control in each of these assays derived from DNA of well-characterized cell lines. The inclusion of such a sample adds an important quality-control parameter to ensure assay-to-assay reproducibility and to satisfy accreditation and regulatory requirements. PMID- 7866639 TI - Value of PCR detection of TCR gamma gene rearrangement in the diagnosis of cutaneous lymphocytic infiltrates. AB - In this study, we analyzed the reliability and usefulness of the polymerase chain reaction (PCR) for the detection of T-cell receptor (TCR)gamma gene monoclonal rearrangement. We first tested for the specificity and sensitivity of this strategy, against the classical criteria of Southern blot analysis (SBA). Of the 27 samples tested, results agreed in all but two. Broader analysis of these cases demonstrated the high specificity (absence of false positives) of the PCR strategy, together with its limited sensitivity (10% of false negatives). The usefulness of this PCR approach was then tested on a panel of 28 biopsy specimens of cutaneous lymphocytic infiltrates. Monoclonal TCR gamma rearrangement was detected in seven of eight cases of early stage mycosis fungoides (MF), one of two Sezary syndrome (SS) cases, two of two non-MF T-cell lymphoma, and two of three lymphomatoid papulosis. Monoclonality was not detected in any of the 11 benign cases (parapsoriasis and inflammatory dermatosis). Results obtained with this new molecular strategy provide additional support for the hypothesis of a monoclonal origin for most early stage T-cell MF. They also suggest the heterogeneous nature of some lymphomatoid papulosis lesions. Therefore, due to the difficulty in detecting T-cell monoclonality by immunohistochemical techniques, PCR can be a useful alternative strategy to SBA. It could also be used as a complementary technique in the routine diagnosis of T-cell cutaneous infiltrates. PMID- 7866640 TI - Comparison of the polymerase chain reaction and Southern blot analysis in detecting and typing human papilloma virus deoxyribonucleic acid in tumors of the lower female genital tract. AB - To conduct studies on the clinical and pathologic significance of human papilloma virus (HPV) in genital malignancies, accurate detection and typing of the virus in clinical material are essential. Currently, Southern blotting and the polymerase chain reaction (PCR) are two of the most commonly used methods to identify HPV. This study was undertaken to compare these techniques in the detection and typing of HPV in 242 invasive malignancies of the lower female genital tract. BamHI and PstI restriction digests of tumor DNA were hybridized to 32P-labeled probes for HPV types 6, 16, and 18 at TM -20 degrees C after Southern transfer. Blots were then washed at Tm -20 degrees C and Tm -9 degrees C. The DNA was also amplified by PCR using both highly conserved consensus L1 primers that detect 25 different HPV genotypes and primers specific for HPV 6 E6, 16 E7, and 18 E6. All PCR products were hybridized to type-specific radiolabeled probes. In 202 of the 242 (83%) samples, HPV was detected, including 189 of 218 (87%) cervical cancers, 11 of the 20 (55%) vulvar cancers, and two of four tumors from the vagina, urethra, or anus. In 67% of the specimens, there was agreement between the Southern blot technique and both methods of PCR (consensus and type specific primers), including 121 of the 202 HPV-positive specimens and 40 HPV negative specimens. Of the 141 tumors with HPV detected by Southern blot analysis, the same HPV type was detected by PCR in 121 (86%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866642 TI - [The duty of documentation by the nursing personnel. Annoying nuisance or important protection?]. PMID- 7866641 TI - Analysis of clonality by amplification of short tandem repeats. Carcinomas of the female reproductive tract. AB - The clonal composition of cancers of the female reproductive tract was evaluated by analysis of patterns of X-chromosome inactivation. Using DNA extracted from frozen tissues or paraffin-embedded archival specimens as template, polymerase chain reaction (PCR) was performed to generate amplified DNA fragments of exon 1 of the X-linked androgen receptor gene, which contains a highly polymorphic trinucleotide repeat. Predigestion of tumor DNA with methylation-sensitive restriction endonuclease Hha I or Hpa II permitted selective PCR amplification from the methylated (uncleaved) allele. Of a total of 54 tumors analyzed, 50 cases showed heterozygosity (93%) and were therefore informative for clonal analysis. Monoclonal composition of the tumors was suggested in a total of 49 of 50 cases, including 12 adenocarcinomas of the uterine endometrium, 13 squamous cell carcinomas of the uterine cervix, 6 adenocarcinomas of the uterine endocervix, and 18 epithelial tumors of the ovary. However, polyclonal composition was observed in one mucinous carcinoma of the ovary, in which we previously showed that both GGT-->GAT and GGT-->GTT mutations are present in > 20% of total K-ras copies in the tissue. Our studies demonstrate the utility of PCR amplification of highly polymorphic repetitive sequences for analysis of patterns of X-chromosome inactivation. This approach is practical for the analysis of clonal cell composition in a high proportion of both formalin-fixed and frozen archival tissues. PMID- 7866643 TI - [Treatment of wounds from today's viewpoint. Don't let acute injuries turn chronic]. PMID- 7866644 TI - [Nurses don't know enough about caring for wounds]. PMID- 7866645 TI - [Alternative wound care. Giving space to being]. PMID- 7866646 TI - [Loss of a baby. Chances for support of mourning parents in the hospital]. PMID- 7866647 TI - [Treating demented patients in Ireland. Group prayer as therapy]. PMID- 7866648 TI - [The Bobath concept in nursing. Exceeding the limits of therapy]. PMID- 7866650 TI - [Evaluation of needs as a basis for the nursing process]. PMID- 7866649 TI - [Alternative management structures. Lean management in the nursing services]. PMID- 7866651 TI - [Indices of nursing. Children--patients--nursing]. PMID- 7866652 TI - 5th International Conference on the Molecular Biology and Pathology of Matrix. Philadelphia, Pennsylvania. June 19-22, 1994. Abstracts. PMID- 7866653 TI - Proceedings of the British Pharmacological Society Meeting. Sunderland, 7-9 September 1994. Abstracts. PMID- 7866654 TI - The destruction of smallpox virus stocks in national repositories: a grave mistake and a bad precedent. PMID- 7866655 TI - Chlamydia trachomatis antigens: role in immunity and pathogenesis. AB - As an intracellular bacteria, Chlamydia trachomatis is an extraordinarily successful pathogen. Chlamydial infections are among the most common of all human infections. Chlamydial disease is less common than infection and is attributed to immune responses to specific antigens of the organism. A major variant surface protein, major outer membrane protein (MOMP), is the principal target of neutralizing antibodies and may be the target of protective immunity. The detailed genetic and immunochemical knowledge of MOMP has stimulated multiple attempts to design an oligopeptide vaccine. Success has been limited in part because of the antigenic variation that the protein exhibits and in part because of the absence of knowledge regarding the three-dimensional structure of the protein. Individuals with severe forms of chlamydial disease often display immune responses to a common chlamydial heat shock protein 60 (hsp60) antigen. Because the protein shares nearly 50% sequence identity with the human homolog, it is speculated that molecular mimacy may result in autoimmune inflammatory damage that in turn causes chlamydial disease sequelae. Because hsp60 immune responses are genetically determined, susceptibility genes for chlamydial disease may also exist. A detailed understanding of the immunobiology of C. trachomatis infection may result from molecular study of chlamydial antigens and the precise nature of immune responses they elicit. Nevertheless, even with the rapid progress that has been made in uncovering the major chlamydial antigens, more remains hidden than revealed. As demonstrated by their successful ecology, chlamydiae remain several stops ahead of even their most ardent pursuers. PMID- 7866656 TI - Etiology and epidemiology of the Four Corners hantavirus outbreak. AB - In May and June 1993, a handful of previously healthy residents of rural areas in the Four Corners region of the southwestern United States died of acute unexplained respiratory distress, later diagnosed as hantavirus pulmonary syndrome. Their illnesses were characterized most prominently by a prodrome of fever and myalgias, followed by thrombocytopenia, the presence of immature white blood cells on the peripheral smear, and catastrophic respiratory decline associated with the sudden onset of noncardiogenic pulmonary edema and hypotensive shock. Although the primary care doctors who treated these patients were spread over a relatively wide rural geographic area, this cluster was recognized in large part because these patients belonged to a defined cohort receiving medical care from a unified system of interconsulting physicians, the Indian Health Service. By just over 2 weeks after receiving laboratory diagnostic specimens, Public Health Service scientists had identified a newly recognized hantavirus as the cause of this disease cluster and Peromyscus maniculatus (the deer mouse) as the rodent reservoir for this zoonotic virus. The oral history of local American Indian healers describes clusters of similar deaths occurring over three cycles during the twentieth century in association with identifiable ecological markers. The abrupt introduction to Western medical practitioners of a disease long recognized by indigenous healers through illness occurring among a cohort of patients seeking care from medical officers of the U.S. Uniformed Services parallels the initial Western medical recognition of previous human illnesses associated with hantaviral infections through disease outbreaks among military troops. The remarkable speed with which the etiology of this disease was elucidated is attributable to both the power of modern genetic investigational techniques and the scientific groundwork laid by nearly half a century of systematic research on hantaviruses. PMID- 7866657 TI - Drug-resistant tuberculosis in adults: implications for the health care worker. AB - In recent years, several outbreaks of drug-resistant tuberculosis have occurred in U.S. hospitals. In response to this recognized risk of tuberculosis exposure in health care facilities, the Centers for Disease Control and the Occupational Safety and Health Administration have issued guidelines or policy procedures for minimizing risks of tuberculosis transmission within these facilities. Some of the recommendations outlined in these governmental documents have been controversial. In this review the guidelines/policies and the debate surrounding them are discussed as they affect the health care worker who cares for adult patients with tuberculosis. PMID- 7866658 TI - Bacterial structure and functional relation to abscess formation. AB - The capsular polysaccharide complex (CPC) of Bacteroides fragilis exhibits unusual biologic properties. This polysaccharide complex promotes the formation of abscesses and prevents abscess induction in a rat model of intra-abdominal sepsis. Each of these biologic properties is mediated by a T cell-dependent immune mechanism. The CPC consists of two distinct polysaccharides, PS A and PS B, each with repeating units that have positively charged amino groups and negatively charged carboxyl or phosphate groups. Analysis of these polysaccharides as well as other charged carbohydrates before and after chemical modification revealed that these oppositely charged groups are required for promotion of intra-abdominal abscesses as well as for protection against abscess induction. These studies provide a structural rationale for the distinct properties associated with the B. fragilis CPC, and delineate one mechanism by which this host response occurs. PMID- 7866659 TI - Overview of issues related to medical compliance with implications for the outpatient management of infectious diseases. AB - Noncompliance with therapeutic drug regimens is a public health problem with major health and economic implications. Reported rates of noncompliance for all types of drugs range from 13% to 93% among adults and from 25% to 82% among children. In recent years, sophisticated techniques for evaluating noncompliance have evolved, as has our understanding of factors associated with noncompliance. A key factor is the prescribed dosing schedule for a drug. Studies indicate that there is a direct relationship between frequency of dose and compliance. A study of compliance with short-term regimens of oral antibiotic therapy found mean compliance rates of 80%, 69%, and 38% for administration once a day (QD), twice a day (BID), and three times a day (TID), respectively. Pharmacoeconomic analyses of dose-related compliance have demonstrated that significant savings can be achieved with QD dosing of antihypertensive medication. Although similar analyses have not been performed for drug regimens used in the treatment of infectious diseases that are usually treated on an outpatient basis, it is probable that comparable savings will be attained when economic analyses of dose/compliance relationships in short-term antibiotic therapy for such common disorders as sinusitis, pharyngitis, otitis media, urinary tract infections, and community acquired pneumonia are undertaken. PMID- 7866661 TI - Effects of nitrogen concentration and cold temperature on DSP-toxin concentrations in the dinoflagellate Prorocentrum lima (Prorocentrales, Dinophyceae). AB - The diarrhetic shellfish poisoning toxin-producing dinoflagellate, Prorocentrum lima, isolated from Nova Scotian waters, contained both okadaic acid (OA) and dinophysistoxin-1 (DTX-1) throughout its growth cycle in culture; maximum concentrations of toxins and highest OA/DTX-1 ratios occurred during the stationary phase. Cells of P. lima survived 0 degrees C for 5 weeks and recovered when brought to a higher temperature. During the cold period, some cell damage probably occurred with concomitant losses of toxins to the medium. Nitrogen concentration in the medium was used to limit growth or stress the cells physiologically, and when growth was limited, increases in toxin associated with the cells were recorded. The relative amounts of okadaic acid were always greater than dinophysistoxin-1, but the significance of these ratios remains to be determined. PMID- 7866660 TI - Growth and toxin production of the toxic dinoflagellate Pyrodinium bahamense var. compressum in laboratory cultures. AB - Toxin production of a Malaysian isolate of the toxic red tide dinoflagellate Pyrodinium bahamense var. compressum was investigated at various stages of the batch culture growth cycle and under growth conditions affected by temperature, salinity, and light intensity variations. In all the experiments conducted, only 5 toxins were ever detected. Neosaxitoxin (NEO) and gonyautoxin V (GTX5) made up 80 mole percent or more of the cellular toxin content and saxitoxin (STX), GTX6 and decarbamoylsaxitoxin (dcSTX) made up the remainder. No gonyautoxins I-IV or C toxins were ever detected. In nutrient-replete batch cultures, toxin content rapidly peaked during early exponential phase and just as rapidly declined prior to the onset of plateau phase. Temperature had a marked effect on toxin content, which increased 3-fold as the temperature decreased from the optimum of 28 degrees C to 22 degrees C. Toxin content was constant at salinities of 24% or higher, but increased 3-fold at 20%. Toxin content decreased 2-fold and chlorophyll content increased 3-fold when light intensity was reduced from 90 to 15 microE m-2 s-1. This accompanied a 30% decrease in growth rate. Toxin composition (mole % individual toxin cell-1) remained constant throughout the course of the nutrient-replete culture and during growth at various salinities, but varied significantly with temperature and light intensity changes. At 22 degrees C, GTX5 was 25 mole % and NEO was 65 mole %, while at 34 degrees C, GTX5 increased to 55 mole % and NEO decreased proportionally to 40 mole %. When light intensity was reduced from 90 to 15 microE m-2 s-1, NEO decreased from 55 to 38 mole %, while GTX5 increased from 40 to 58 mole %. These data suggest that low light and high temperature both somehow enhance sulfo-transferase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866662 TI - Domoic acid-producing diatom blooms in Monterey Bay, California: 1991-1993. AB - During the autumn of 1991, numerous seabird fatalities in Monterey Bay, California, led to the discovery of a new domoic acid-producing diatom, Pseudonitzschia australis. Since this initial event, sizable populations of P. australis, as well as other likely toxin producers, P. pungens f. multiseries and P. pseudodelicatissima, have occurred biannually in Monterey Bay. Using the highly sensitive FMOC-HPLC method, we detected domoic acid whenever Pseudonitzschia australis was found in the plankton, even at densities as low as 4.0 x 10(3) cells/L. Based on correlations of domoic acid and P. australis abundances and the overwhelming biovolume dominance of P. australis, we conclude that P. australis has been the major domoic acid producer during the period of our study. Our study suggests that P. australis cells may always be toxic in natural populations and that toxin concentrations on a per cell basis have no statistically significant relationship to population density or to nutrient concentrations other than silicate. Cellular levels of domoic acid were positively correlated with silicate concentrations, which is at variance with reports from prior culture experiments. These conclusions must be tentative because of the limited extent of our sampling. Nevertheless, these preliminary data indicate that further investigations of environmental conditions affiliated with cell growth and toxin production in P. australis are warranted. As a practical matter, domoic acid in the pelagic environment cannot be reliably or consistently detected by monitoring domoic acid levels in intertidal mussels. Direct measurement of domoic acid using sensitive HPLC methods is probably the most cost-effective and accurate approach for an ongoing phycotoxin monitoring program. PMID- 7866663 TI - Scytophycin production by axenic cultures of the cyanobacterium Scytonema ocellatum. AB - Nonaxenic clones prepared from the cyanobacterium Syctonema ocellatum Lyngbye ex Bornet et Flahault strain FF-66-3 exhibited a high degree of heterogeneity with respect to tolytoxin titer. Thirty-four of 114 clones (29.8%) isolated by fragmentation of Scytonema filaments did not produce detectable amounts of tolytoxin in culture. One clone (designated SO127) produced approximately twice as much tolytoxin as the parental culture and continued to produce tolytoxin after repeated subculture. Three axenic clones were prepared from SO127 by a combination of antibiotic treatment and mechanical separation. Although axenic cultures yielded slightly greater biomass, tolytoxin content did not significantly differ between axenic and nonaxenic cultures, indicating that bacteria do not play a role in tolytoxin biosynthesis. Bacterial cultures derived from S. ocellatum did not produce detectable amounts of tolytoxin. PMID- 7866664 TI - Kainic acid and 1'-hydroxykainic acid from Palmariales. AB - The distribution of kainic acid among various red algae was investigated. Analysis of free amino acids from different populations of Palmaria palmata showed that some were unable to accumulate kainic acid to detectable concentrations, whereas in two dwarf mutants it was a major component of the free amino acid composition. The amino acid profiles were also examined for unknown amino acids in the search for possible intermediates in kainic acid biosynthesis. The only unknown amino acid present in P. palmata extracts was isolated and identified by NMR spectroscopy as 1'-hydroxykainic acid. This compound was found in all samples that contained kainic acid. To investigate the effect of growth conditions on kainic acid production different strains of P. palmata were grown at 5, 10, and 15 degrees C with or without added nitrate. No effect on production was observed, suggesting that the growth conditions in these experiments do not affect the level of gene expression in the pathway of kainic acid biosynthesis. Furthermore, changing the growth conditions did not induce synthesis of kainic acid in the non-producing strains of Palmariales. PMID- 7866665 TI - Highly sensitive assay of okadaic acid using protein phosphatase and paranitrophenyl phosphate. AB - A colorimetric phosphatase-inhibition bioassay was developed for the quantitative measurement of okadaic acid (OA) the main diarrhetic toxin responsible for diarrhetic shellfish poisoning. The assay used an artificial substrate, paranitrophenylphosphate, and a semi-purified protein phosphatase PP2Ac containing extract prepared from rabbit muscle. Calibration dose-inhibition curves were constructed using standard OA and they permitted easy determination of the enzyme concentration Et in their linear portion. In the range of linearity, the slope increased when Et decreased, thus giving a detecting limit of 0.04 pmol in the reaction mixture (1 ml). The lowest assayable concentration of OA was 4 ng/ml in aqueous solutions and 40 ng/ml (i.e., 100 ng of OA per g of mussel tissue) in crude methanol mussels extracts. The intra and interassay coefficients of variation in the measurement of OA for the toxin spiked aqueous samples averaged, respectively, 7.7% and 3.7%, and interexperiments coefficients of variation for the toxin spiked mussel extracts averaged 4.6%. The presence of OA was ascertained by a method in which one assay was performed at two or three different levels of enzyme concentration. The rapidity, accuracy, reproducibility, specificity, and simplicity of the procedure provides a simple way to assay okadaic acid in buffered or complex solutions. PMID- 7866666 TI - Investigation of derivatization reagents for the analysis of diarrhetic shellfish poisoning toxins by liquid chromatography with fluorescence detection. AB - Several derivatization reagents for the conversion of okadaic acid and related DSP toxins to fluorescent derivatives for analysis by liquid chromatography have been examined, viz: 9-anthryldiazomethane (ADAM), 1-pyrenyldiazomethane (PDAM), 4 diazomethyl-7-methoxycoumarin (DMMC), 4-bromomethyl-7-methoxycoumarin (BrMMC), 4 bromomethyl-7,8-benzcoumarin (BrMBC), 4-bromomethyl-7-acetoxycoumarin (BrMAC), and 4-bromomethyl-6,7-dimethoxycoumarin (BrDMC). The ADAM reagent provides the greatest selectivity and sensitivity, but its application on a routine basis has been limited by its instability and cost. Improvement of this method was achieved through the production of ADAM in situ from the stable 9-anthraldehyde hydrazone. A detection limit of 30 ng/g hepatopancreas (equivalent to 6 ng/g whole tissue) was achieved. The other aryldiazomethane reagents were found to have insufficient reactivity. Of the bromomethylcoumarin reagents, BrDMC was found to have the greatest promise. The reagent is inexpensive and has excellent stability and purity. Quantitative derivatization may be achieved in a 2 hour reaction at 45 degrees C with N,N-diisopropylethylamine as a catalyst. Unfortunately, the lower reaction selectivity of BrDMC compared to that of ADAM limits its application to isolated toxins, plankton samples, and shellfish tissues with high levels of DSP toxins. The use of BrDMC for the determination of how toxin levels in shellfish tissues will require development of a more extensive clean-up prior to derivatization. Successful application of the ADAM and coumarin derivatization methods to real-world samples has been demonstrated. PMID- 7866667 TI - Studies on the detection of okadaic acid in mussels: preliminary comparison of bioassays. AB - Diarrheic toxins, especially okadaic acid, are detected nearly every year in mussels on French coasts. The monitoring network determines the toxicity of these shellfish by using a mouse test now considered unsatisfactory from an ethical point of view. Two alternative methods have been investigated: the daphnia test, for which there is a standardized method used routinely in ecotoxicology, and a cytotoxicity test on the KB cell line developed for this study. Using the same samples, the results of these two tests were compared with those obtained by chemical analysis (HPLC okadaic acid assay) or the mouse test. Linear regression studies showed that results for the two bioassays were well correlated with those for HPLC or the mouse test. PMID- 7866668 TI - An incident of elevated levels of unsaturated free fatty acids in mussels from Nova Scotia and their toxic effect in mice after intraperitoneal injection. AB - Methanol extracts of the hepatopancreas of mussels (Mytilus edulis) harvested at two locations (Ship Harbour and Wine Harbour) in eastern Nova Scotia, Canada, were found to be toxic to mice after intraperitoneal injection. The commonly known toxins, such as those associated with diarrhetic shellfish poison (DSP), paralytic shellfish poison, and domoic acid, were not present in the extracts. However, they were found to contain elevated levels of free fatty acids. Using a modified DSP extraction procedure the quantities of free fatty acids determined (by latroscan TLC/FID) in the hepatopancreases of mussels were 2.9 mg/g (Ship Harbour 1), 2.2 mg/g (Ship Harbour 2), 1.2 mg/g (Wine Harbour), and 0.15 mg/g (Prince Edward Island, control). After further investigation it was determined that certain unsaturated fatty acids were mainly responsible for the toxicity. These included palmitoleic, linoleic, linolenic, octadecatetraenoic, and eicosapentenoic acids. Artificial mixtures of pure standards of these acids prepared in the same concentrations as found in the shellfish samples were also toxic to mice. These results indicate that elevated levels of free fatty acids in mussel hepatopancreas from locations in eastern Canada can lead to mouse deaths when using the DSP mouse bioassay procedure. PMID- 7866669 TI - Selection of cytotoxic responses to maitotoxin and okadaic acid and evaluation of toxicity of dinoflagellate extracts. AB - The cytotoxicity of maitotoxin (MTX) and okadaic acid (OA) was studied on three mammalian fibroblast cell lines. Neutral red uptake (NRU), which measures cell viability, and morphological alterations were selected as rapid suitable responses. NRU allowed a precise toxicity quantification while the observations of morphological damage revealed differences specific to MTX (cell blebbing) and OA (cell rounding). BHK21 C13 fibroblasts, although less sensitive to MTX than the other cell lines, were chosen since they gave stable information and a two stage morphological response with OA ("square"-shaped cells, then round cells). When NRU and morphology alterations were studied with crude extracts of Gambierdiscus toxicus and Prorocentrum lima, responses were typical of the dominant toxins, MTX and OA or related toxins respectively. Applied to several dinoflagellate extracts, the two tests revealed no toxicity for Amphidinium carterae, Ostreopsis siamensis, O. ovata and Coolia monotis (from La Reunion) and toxicity for A. carterae and A. operculatum (from Saint Barthelemy). When toxic, A. carterae extracts showed blebbing similar to that caused by MTX. Morphology alterations caused by A. operculatum crude extracts, different from those corresponding to MTX or OA, were also observed. PMID- 7866670 TI - Kinetics of Alexandrium minutum Halim toxin accumulation in mussels and clams. AB - Mussels (Mytilus edulis) and clams (Ruditapes philippinarum) were contaminated experimentally using cultures of Alexandrium minutum, a toxic dinoflagellate isolated from French coastal waters. Experiments were carried out in continually flushed and open-circuit systems using Alexandrium densities of 100 to 700 cells/ml delivered to tanks containing the shellfish. All experiments indicated an inversion of the relative proportions of gonyautoxins (GTX2 and GTX3) in shellfish meat during decontamination, whereas saxitoxin (STX) only accumulated during mussel depuration. However, in mussels a density as low as 100 cells/ml led within 10 days to bioaccumulation of paralytic shellfish poisoning (PSP) toxins above the public health threshold. Similar results were observed in clams subjected to fivefold higher cell densities, indicating a less effective assimilation of the dinoflagellate than by mussel. Decontamination experiments on PSP toxin-contaminated mussels (360 micrograms STX eq./100 g or lower uptake) fed two nontoxic diets (1,000 and 10,000 cells/ml of Tetraselmis suesica) showed an appreciable reduction in the time needed to decrease toxin concentration below the accepted threshold for human consumption. We suggest that a simple relation can be established between initial toxicity, the concentration of nontoxic alga available, and the time required for depuration once decontamination kinetics becomes linear and corresponds to the inverse of contamination kinetics. PMID- 7866671 TI - Toxicology and seafood toxins: domoic acid. AB - Marine and terrestrial food sources are susceptible to contamination by various industrial chemicals and microbial pathogens. Both types of hazard are amenable to regulatory assessment using a single toxicology data base, along with some knowledge of contaminant levels and consumption figures for food. On the other hand, regulatory problems persist with acutely toxic naturally occurring phycotoxins, which may accumulate unpredictably to toxic levels in seafood. However, a scarce supply of pure toxin often precludes the availability of acceptable toxicology studies describing their biological effects. An exception to this situation is domoic acid, a neurotoxin phycotoxin that produced numerous cases of severe human intoxication which demanded extensive toxicological study. This paper describes a series of ongoing studies initiated in the wake of the outbreak of domoic acid toxicity that occurred in 1987 in Eastern Canada. PMID- 7866672 TI - Linguistics in a neuropsychiatric frame. A look at the dialogue of brain and mind. PMID- 7866673 TI - Linguistics, human communication and psychiatry. AB - BACKGROUND: Psycholinguistics and sociolinguistics have extended our understanding of the abnormal communication seen in psychosis, as well as that of people with autism and Asperger's syndrome. Psycholinguistics has the potential to increase the explanatory power of cognitive and neuropsychological approaches to psychosis and new methods of assessment and therapy are now being developed, based on linguistic theory. METHOD: A MEDLINE literature search was used. RESULTS: Of 205 relevant articles identified, 65 were selected for review. CONCLUSIONS: Greater familiarity with linguistic theory could improve psychiatrists' assessment skills and their understanding of the relevance of human communication to the new cognitive models of psychosis. PMID- 7866674 TI - Predictors of psychiatric morbidity in cancer patients. AB - BACKGROUND: A significant proportion of cancer patients experience psychiatric morbidity in association with diagnosis and treatment. If this morbidity is to be reduced, a better understanding is needed of the factors which influence adjustment to cancer. METHOD: A review of the literature was carried out to explore those factors associated with poor psychological adjustment to cancer. These are described under four heading: characteristics of the patient; disease and treatment variables; the interaction between patient and illness; and environmental factors. RESULTS: A number of risk factors for psychiatric morbidity can be identified from each of the four areas. Methodological limitations are highlighted, in particular the preponderance of cross-sectional study designs. CONCLUSIONS: Increased awareness of the risk factors for psychiatric morbidity should lead to earlier detection and more appropriate treatment. Future research should focus on those risk factors which are potentially modifiable. PMID- 7866675 TI - Psychosurgery: stereotactic subcaudate tractomy. An indispensable treatment. AB - BACKGROUND: Stereotactic subcaudate tractotomy (SST) is the only type of psychosurgery performed at the Geoffrey Knight Unit, London, where nearly 1300 operations have been done since 1961. Statistically reliable data are not available to prove the effectiveness of SST. A detailed statement about contemporary psychosurgery is given. METHOD: Relevant publications from the Unit and via Medline are discussed. The outcome figures are reviewed. The outcome is assessed at the Unit in global and clinical terms, associated with results of self-completed questionnaires. RESULTS: SST allows 40-60% of patients to live normal or near-normal lives, perhaps with continuation of medication. A reduction in suicide rate to 1% post-operatively, from 15% in cases of uncontrolled affective disorders is seen. CONCLUSION: As a treatment of last resort, no controlled trial against a comparable treatment is possible. It appears reasonable to offer SST to patients with suicidal and deluded depression or with frequently swinging moods, not responding to other treatments. PMID- 7866676 TI - The pathological extensions of love. AB - BACKGROUND: Clarification is still required of the nature of pathological love. METHOD: A series is presented of 16 personally assessed cases with pathologies of love (erotomania). RESULTS: The pathologies of love usually involve a mixture of morbid infatuation and a morbid belief in being loved. They occur both in a symptomatic form, as part of an underlying mental illness, as well as in a pure form, where their emergence is to some extent understandable in a vulnerable personality. These disorders often go unrecognised to the detriment of clinical management. CONCLUSIONS: Pathologies of love create distress and disruption to the patient, and place the objects of their unwarranted affection at risk of at best harassment and at worst violence. Although this series of cases, which is drawn predominantly from forensic practice, overemphasises the risk of overt violence, the distress occasioned by pursuit and harassment alone should not be underestimated. PMID- 7866677 TI - Sexual murder. AB - BACKGROUND: Little is known about men who kill in a sexual context. The present study compares a group of sexual murderers with a group of men who had raped but not killed. METHOD: Twenty-one men who murdered women in the course of a sexual attack and 121 men convicted of rape were interviewed in six prisons. Victim statements were obtained in 103 cases (73%). Assessment consisted of a 90-minute semi-structured interview, the Eysenck 1-7 questionnaire, and the Schonell reading test. RESULTS: The most notable characteristic distinguishing the men who killed was their lifelong isolation and lack of heterosexual relationships. CONCLUSIONS: A better understanding of the social and emotional isolation commonly found in sexual murderers may provide important insights into why some sexual offenders go on to kill. PMID- 7866678 TI - Male mentally handicapped sex offenders. AB - BACKGROUND: Sex offences are overrepresented in the mentally handicapped, but information about the characteristics and offence behaviour of this group is limited. METHOD: A retrospective case note survey was made of 47 male patients referred for antisocial sexual behaviour. RESULTS: Of 191 offences and/or incidents committed, 55.5% were heterosexual, 24% indecent exposure, 12.4% homosexual, 13.6% serious and 3.6% involved physical assault. Average age of the offenders was 23.9 years, with a mean IQ of 59.5, and there was a high prevalence of family psychopathology, psychiatric illness, minor physical disabilities, sexual experience, impaired relationship skills and sexual recidivism. Recidivists showed a low specificity for offence type and age and sex of victim. Categorical analysis differentiated a 'sex offences only' group from a 'sex plus other offences' group in the key areas of psychopathology, offence behaviour and outcome; this was supported by factor analysis. CONCLUSION: The finding of two subgroups of mentally handicapped male sex offenders has important implications for prevention, assessment and treatment. PMID- 7866679 TI - Recognition of mental state terms. Clinical findings in children with autism and a functional neuroimaging study of normal adults. AB - BACKGROUND: The mind's ability to think about the mind has attracted substantial research interest in cognitive science in recent decades, as 'theory of mind'. No research has attempted to identify the brain basis of this ability, probably because it involves several separate processes. As a first step, we investigated one component process-the ability to recognise mental state terms. METHOD: In Experiment 1, we tested a group of children with autism (known to have theory of mind deficits) and a control group of children with mental handicap, for their ability to recognise mental state terms in a word list. This was to test if the mental state recognition task was related to traditional theory of mind tests. In Experiment 2, we investigated if in the normal brain, recognition of mental state terms might be localised. The procedure employed single photon emission computerised tomography (SPECT) in normal adult volunteers. We tested the prediction (based on available neurological and animal lesion studies) that there would be increased activation in the orbito-frontal cortex during this task, relative to a control condition, and relative to an adjacent frontal area (frontal-polar cortex). RESULTS: In Experiment 1, the group with autism performed significantly worse than the group without autism. In Experiment 2, there was increased cerebral blood flow during the mental state recognition task in the right orbito-frontal cortex relative to the left frontal-polar region. CONCLUSIONS: This simple mental state recognition task appears to relate to theory of mind, in that both are impaired in autism. The SPECT results implicate the orbito-frontal cortex as the basis of this ability. PMID- 7866680 TI - The function of the hypothalamic-pituitary-adrenal axis in Alzheimer's disease. Response to insulin hypoglycaemia. AB - BACKGROUND: To investigate an association between HPA axis dysfunction, depression and cognitive impairment, we assessed subjects with mild Alzheimer's disease (AD). METHOD: Sixteen non-depressed subjects with AD according to NINCDS/ADRDA criteria and 18 normal controls underwent the insulin hypoglycaemia (IH) test and the dexamethasone suppression test (DST). RESULTS: The AD subjects showed a blunted response of adrenocorticotrophic hormone (ACTH) to IH compared with controls (P = 0.019). ACTH response (area under curve) correlated with a score for cognitive ability (CAMCOG) (r = 0.64, P < 0.01). AD subjects had a shorter time to peak cortisol level than controls (P = 0.004), although total cortisol response was normal. CONCLUSIONS: The AD subjects show evidence of adrenal hyper-responsiveness and normal immediate (rate-sensitive) glucocorticoid feedback. An association between HPA axis dysfunction and organic brain pathology in AD subjects may be mediated by cell loss in the hippocampus. PMID- 7866682 TI - Prediction of outcome following a first episode of schizophrenia. A follow-up study of Northwick Park first episode study subjects. AB - BACKGROUND: Although previous studies have attempted to identify predictors of outcome in schizophrenia, few have prospectively studied first episode patients for an adequate follow-up period. METHOD: The psychopathological predictors of outcome were investigated in a subgroup of 51 subjects, originally included in the Northwick Park study of first episode schizophrenia who were followed up 7.3 years (s.d. 1.1, range 5.3-10.3) after first admission in the Harrow study. Forty four subjects (24 men, 20 women) were traced. Outcome measures were time to first readmission, occupational level and total duration of hospital admission at five years after first admission. RESULTS: A survival analysis of time to first relapse revealed that the presence of subjective feelings of depression (CATEGO syndrome SD) during the first admission was associated with early relapse while the presence of depressive delusions (CATEGO syndrome DD) and higher educational attainment protected against early relapse. Total duration of hospitalisation at five years after first onset was positively associated with the presence of CATEGO syndromes SD and OD (biological features of depression) and negatively associated with female sex. Poor occupational outcome was not significantly associated with any psychopathological predictors. CONCLUSIONS: Our findings challenge the conventional view that symptoms of depression are associated with better outcome in schizophrenia. PMID- 7866681 TI - Suicide in the mentally ill. An epidemiological sample and implications for clinicians. AB - BACKGROUND: Information on risk factors associated with high rates of suicide is necessary, if suicide rates among the mentally ill are to be reduced. METHOD: We used ICD-9 E-codes to define deaths on which suicide or open (undetermined death) verdicts were returned, among residents of a catchment area defined by OPCS area codes. Relative risks of suicide and undetermined deaths for recent patients (those in contact with a psychiatric service in the year preceding death) were calculated. RESULTS: Of the 286 persons, 108 were recent patients. Eighty-four per cent suffered from schizophrenia or depression. Risks of suicide and undetermined death for these patients were 31 and 20 times, respectively, those of other residents. Social risk factors varied with diagnosis. CONCLUSION: Over 90% of recent patients were receiving medical care at time of death; not all were treated appropriately. Recognising medical and social risk factors in recent patients, and effective monitoring of treatment, is important. PMID- 7866684 TI - Understanding the symptoms of schizophrenia using visual scan paths. AB - BACKGROUND: This paper highlights the role of the visual scan path as a physiological marker of information processing, while investigating positive symptomatology in schizophrenia. METHOD: The current literature is reviewed using computer search facilities (Medline). RESULTS: Schizophrenics either scan or stare extensively, the latter related to negative symptoms. Schizophrenics particularly scan when viewing human faces. CONCLUSIONS: Scan paths in schizophrenics are important when viewing meaningful stimuli such as human faces, because of the relationship between abnormal perception of stimuli and symptomatology in these subjects. PMID- 7866683 TI - A validity study of the Hospital Anxiety and Depression Scale in general hospital units and a community sample in Nigeria. AB - BACKGROUND: The utility of the Hospital Anxiety and Depression Scale (HADS) as a screening instrument for anxiety and depressive disorders in non-psychiatric units (medical & surgical wards; gynaecology & antenatal clinics of a teaching hospital) and a community sample in Nigeria was investigated. METHOD: A two-stage screening procedure was employed. This involved the use of GHQ-12/GHQ-30 and HADS against the criteria of a standardised (PSE schedule) psychiatric interview, with psychiatric diagnosis assigned in accordance with ICD-9 criteria. RESULTS: Sensitivity for the anxiety sub-scale ranged from 85.0% in the medical and surgical wards to 92.9% in the ante-natal clinic, while sensitivity for the depression sub-scale ranged from 89.5% in the community sample to 92.1% in the gynaecology clinic. Specificity for the anxiety sub-scale ranged from 86.5% in the gynaecology clinic to 90.6% in the community sample, while specificity for the depression sub-scale ranged from 86.6% in the medical and surgical wards to 91.1% in the ante-natal clinic and community sample. Misclassification rates ranged from 9.9% in the community sample to 13.2% in the medical and surgical wards. Relative Operating Characteristic (ROC) analyses showed the HADS and the GHQ-12 to be quite similar in ability to discriminate between cases (anxiety and depression) and non-cases. CONCLUSIONS: The HADS is valid for use as a screening instrument in non-psychiatric units and although initially developed for use in hospital settings, it could be usefully employed in community settings of developing countries to screen for mental morbidity. PMID- 7866685 TI - Childhood sexual experiences with adults: adult male psychiatric patients and general practice attenders. AB - BACKGROUND: Sexual abuse of male children is now believed to be common, and there may be links to adult psychiatric disorders. METHOD: Recollections of sexual experiences with adults in childhood were studied systematically in 115 men attending general practice surgeries and 100 male psychiatric patients. RESULTS: The latter reported more frequent and more serious events before the age of 13 than the general practice attenders. No significant difference was detected for events between the ages of 13 and 15. CONCLUSIONS: Childhood sexual abuse before the age of 13 may be associated with later psychiatric disorders, although the nature of the association remains uncertain. The possible significance of such experiences should be considered when assessing men with mental disorders. PMID- 7866686 TI - The reliability and validity of the proposed axis V (disabilities) of ICD-10. AB - BACKGROUND: The purpose of this study was to examine the reliability and validity of the newly proposed axis V (disabilities) of ICD-10. METHOD: Eighty-six acutely ill men and women were prospectively recruited from the Al Ain psychiatric units, UAE. Both versions of ICD-10, the Clinical Descriptions and Diagnostic Guidelines and the Diagnostic Criteria for Research (DCR) were used for coding axis I psychiatric diagnosis and its grade of severity; the WHO Disability Assessment Schedule was used to assess disabilities. RESULTS: Inter-rater reliability of the DAS items ranged from moderate to good, and axis V ratings correctly predicted 84% of the observed classification on axis I. CONCLUSION: Axis V is a valid measure of disabilities, but is limited by its modest reliability. PMID- 7866687 TI - Amok. AB - BACKGROUND: Amok is reviewed from a historical standpoint, tracing how it has changed from the Hindu states of India where it was a war tactic to the sudden incomprehensible violence and mass murder by a single individual associated with the syndrome today. METHOD: A typical amok attack is described and the criteria for amok discussed. Amok in Malaysia, New Guinea, Laos, North America and other countries are presented. The possible motives for such violent killings and a possible psychiatric diagnosis in relation to contemporary diagnostic criteria is discussed. CONCLUSION: Classification of amok remains unresolved. The reason for its frequency in and around Malaysia remains unknown. PMID- 7866688 TI - Henry Maudsley on Swedenborg's messianic psychosis. AB - BACKGROUND: Creativity, religiosity and madness have long been thought to be aetiologically interrelated. METHOD: Henry Maudsley's little known pathography of the 17th century Swedish philosopher and polymath, Emanuel Swedenborg, was examined. RESULTS: Swedenborg developed a messianic psychosis in middle life, considered by Maudsley to be a monomania, possibly due to epilepsy. Many of Swedenborg's contemporaries thought of him, however, as a religious eccentric. Under criticism from Swedenborg's followers, Maudsley avoided further reference to Swedenborg, and the pathography was lost from view. CONCLUSIONS: Renewed interest is deserved in the contentious issues of the nature of religiosity and its relationship to psychotic experience. PMID- 7866689 TI - Suicide prevention in Gotland. PMID- 7866690 TI - Defeating depression in Zimbabwe. PMID- 7866691 TI - Chromosomal aberration and bipolar affective disorder. PMID- 7866692 TI - Genetics, chance and dysmorphogenesis in schizophrenia. PMID- 7866693 TI - Cognitive-behavioural therapy for schizophrenia. PMID- 7866694 TI - Anorexia nervosa and schizophrenia. PMID- 7866695 TI - Mental handicap and the pandemic influenza. PMID- 7866696 TI - Ejaculation associated with zuclopenthixol. PMID- 7866697 TI - Sleep disturbance in schizophrenia. PMID- 7866698 TI - What is existential psychotherapy? PMID- 7866699 TI - Antigenic variation of surface proteins as a survival strategy for bacterial pathogens. PMID- 7866700 TI - Molecular genetics of pathogenic fungi: new horizons. PMID- 7866701 TI - Animal models of Lyme disease: pathogenesis and immunoprophylaxis. AB - Valuable insights into the pathogenesis and immunoprophylaxis of Lyme disease are beginning to emerge from studies in animal models. This review highlights two animal models: the mouse, which has allowed us to investigate the role of both the immune response and spirochete phenotype in determining the outcome of the disease; and the Rhesus monkey, which manifests signs of nerve involvement, in addition to showing erythema migrans and arthritis. PMID- 7866702 TI - How bacteria resist killing by host-defense peptides. AB - Small cationic peptides with antimicrobial properties are part of the innate immune response of a wide variety of animal species, including insects, amphibians and mammals. Bacterial pathogens have evolved distinct mechanisms to avoid, inactivate or resist the killing effects of these peptides. Determinants necessary for resistance to peptides often contribute to the virulence properties of recognized pathogens. PMID- 7866703 TI - The 5' noncoding region and virulence of poliovirus vaccine strains. AB - All three live, attenuated vaccine strains of poliovirus contain important attenuation determinants in a short conserved sequence in the 5' noncoding region. Evidence suggests these act by weakening a secondary-structural element critical for the unusual mechanism of translational initiation of picornaviruses, in which ribosomes bind directly to a site far downstream of the 5' end. Understanding the molecular basis of attenuation may allow novel vaccine strains to be designed. PMID- 7866704 TI - Mechanisms of sexual transmission of HIV: does HIV infect intact epithelia? AB - The prevailing view of sexual transmission of HIV has been that the virus enters the body through lesions in the epithelium of the genital tract. We propose that transmission of HIV can occur via the infection of intact epithelial cells, and that it is mediated by HIV-infected mononuclear cells in genital-tract secretions. PMID- 7866705 TI - Applying the findings of clinical trials to individual patients. PMID- 7866706 TI - Increased oxygen delivery for high-risk surgery. PMID- 7866707 TI - [Role of neurologic sciences in occupational medicine]. AB - The article presents possible neural disorders caused by occupational hazards and shows mechanisms underlying those disorders. The authors define topical problems of basic science related to occupational neurology, which require further studies with neurochemical, immunologic, neurophysiologic methods and comparison. PMID- 7866708 TI - [How to manage occupational cramp]. AB - The article deals with some diagnostic traits of local dystonia (dyscoordination neurosis) in musicians, which is caused by occupational strain. Unsatisfactory biomechanics of the musicians fingers and hands appeared to be negative effects, the special role in occupational crasp formation was proved for imperfect flexibility of the hands. Other risk factors could be overload of the hands, resulting from higher motivation for success and improvement, false position of the hands and consequent static strain of the participating muscles, trauma to the hands. Occupational crasp and local dystonia are considered to differ from hysteria manifestations in musicians. Some recommendations are given for musicians and their teachers to prevent possible occupational crasp and local dystonia. PMID- 7866709 TI - [Development of occupational vertebral radiculopathies and tunnel syndromes]. AB - The study proved occupational and everyday strain of muscles and ligaments to be risk factor for ischemic and compression neuropathy. The pathologic changes appeared to involve not only compression points, but also the sites distant from the primary area and ultimately the whole axon. Therefore, spinal roots and nerves could be affected by complicated and multiple ischemic and compression radiculopathies demonstrating typical clinical signs. PMID- 7866710 TI - [Effect of biotechnological industrial factors on immune system reactivity]. AB - Screening in employees of enterprise producing antibiotics has revealed higher occurrence of allergic (39.6%) and gastrointestinal diseases. Some examinees (5.4%) demonstrated immune deficiency, the share of 8.3% were diagnosed as having cardiovascular neurosis. Further investigations involved bioluminescent and cytochemical studies of oxidation-reduction enzymes in white blood cells. Those studies proved lower serum activity of the enzymes in all the examinees including apparently healthy individuals. There was no significant difference between the health and ill employees, apart from the patients with immune deficiency. Ratio of CA to serotonin concentrations in the cells provided the most valuable information, being a diagnostic criterion for the diseases mentioned. PMID- 7866711 TI - [Silicosis]. PMID- 7866712 TI - [Formation of occupational groups for the primary prevention of diseases in railroad workers]. AB - Long-term studies helped to group all railway occupations according to similar occupational and industrial hazards and to morbidity levels. The authors elaborated the main principles of primary prophylaxis for those occupations, considering all the hazards, morbidity levels and economic features. PMID- 7866713 TI - [Perinatal care for the fetus in women exposed to ionizing radiation after the Chernobyl nuclear plant accident]. AB - Thorough examination covered 114 pregnant women living in the second zone of radioactive pollution (Novozybkov town in Briansk region). Occurrence of miscarriage, late gestosis, intrauterine hypoxia and hypotrophia of fetus was higher vs. control. Laboratory studies helped to reveal underlying mechanisms of the stated conditions which are caused by compromised immunity and changes in fetoplacental system. PMID- 7866714 TI - [Early detection of chronic dust-induced bronchitis in the workers of coal mines in Rostov region]. AB - To diagnose mild forms of dust bronchitis in miners, the medical examination covered pulmonary ventilation parameters. The examination revealed bronchial obstruction, so early stages of bronchitis became 2-2.5 times more frequently diagnosed. Registration of flow-volume curve in forced expiration appeared to be the most productive functional test. PMID- 7866715 TI - [Eye changes among workers in the construction materials industry]. PMID- 7866716 TI - [Effect of work conditions on the development of vertebral neurologic disorders]. AB - Clinical and hygienic studies covered agricultural machine operators, bulldozer operators, truck drivers, excavator and boring machine operators, display terminal controllers, electronic miniature device assemblers. The studies proved that occupational hazards (general vibration, sitting posture) result in formation of vertebral neurologic disorders in the examinees. The localization and clinical manifestations appeared to depend on intensity and site of the acting hazard. PMID- 7866717 TI - [Scientific conference of the Russian Academy of Medical Sciences "Chemistry and health. II. Toxic effects of pollutants"]. PMID- 7866718 TI - [International symposium on transport medicine "Diseases, treatment of drivers and traffic accidents"]. PMID- 7866719 TI - [Effect of organic solvents on functional nervous system disorders]. AB - Examination of 953 workers exposed to low concentrations of chlorbenzene, tricresol and dimethylfonnamid revealed such functional neural disorders as cardiovascular neurosis. Chlorbenzene and tricresol resulted in hypertonic cardiovascular neurosis, dimethylformamid--in hypotonic one. Occurrence of cardiovascular neurosis grew with the longer length of service. PMID- 7866720 TI - [Clinical and hygienic evaluation of the combined effect of vibration and fluoride in humans]. AB - Hygienic evaluation of work conditions and clinical examination of workers in fluoride mines proved vibration disease to be the prevalent occupational entity in those employees. Caused by joint effects of vibration and fluor, the clinical signs in this context demonstrate short development, occupational disablement and possible connection with fluorosis. Joint effects of vibration and calcium fluoride vs. influence of the isolated hazards show more compromised functions and changes of fluor kinetics in the body. PMID- 7866721 TI - The structure and function of the first component of complement: genetic engineering approach (a review). AB - The availability of cDNA and genomic clones for the subcomponents of C1, as well as the recognition of the modular organization of serine-proteases have opened up exciting new possibilities for approaching structural problems. In this review the latest achievements of combined protein engineering, functional and structural studies are summarized. The concept of this research is to construct deletion, point and hybrid mutants of the highly homologous C1r and C1s subcomponents, to reveal the functional role of individual modules, map the interaction sites between subcomponents of the C1 complex and refine the structural model of C1. The first prerequisite of such an approach was the expression of the subcomponents in a eukaryotic system, in biologically active form. This was followed by expression of various mutants. Autographa californica nuclear polyhedrosis virus was used as vector to express human C1r and C1s in Spodoptera frugiperda cell culture and in lepidopteran larvae. The yield of expression was high enough to isolate recombinant subcomponents for structural and functional studies. Recombinant viruses containing the A-, B-, and C-chains of C1q were also constructed. The insect cells are able to beta-hydroxylate the Asn residue of the EGF domain in the C1r but with a low efficiency. It is clear now, that this post-translational modification does not play a role in the Ca2+ dependent C1r-C1s interaction. The results with deletion mutants of C1r show that both, domain I, and II are absolutely necessary for the tetramer formation and both have regulatory role in the autoactivation. The C1s alpha R hybrid does not dimerize in presence of Ca2+, however it can form a tetramer with C11(2) that can bind to C1q. This observation indicates that the function of the C1s alpha part in the hybrid is modulated by the C1r part (gamma B) of the molecule. The C1Rs hybrid behaves like C1r, providing haemolytically active C1 with C1q and C1s. This observations shows that the regulatory domains determine the high functional specificity of the serine-protease subcomponents of C1. In order to control the autoactivation process point mutant cDNAs were constructed by altering the Arg Ile bond in the catalytic domain of the C1r. The Gln-Ile construction is a stable zymogen while the Arg-Phe mutant has a lower rate of autoactivation. PMID- 7866722 TI - Transfer and establishment of DNA in Streptomyces (a brief review). AB - Based on endogenous Streptomyces plasmids we have constructed various multiple purpose vectors for cloning in streptomycetes. Since replication of the S. ghanaensis plasmid pSG5 is inherently temperature-sensitive, pGM-vectors derived from pSG5 can be used for gene disruption/replacement and mutational cloning. The 1.6-kb minimal replication region of pSG5 encodes only one polypeptide, an initiation protein (Rep) for single stranded DNA-replication. Different internal fragments of sequenced genes of the Ptt-biosynthetic pathway were cloned into pGM vectors to study both, the function of the biosynthetic genes and recombination in Streptomyces. The observed recombination frequencies were very high, up to 80% of the cells carried single or multiple copies of the plasmid integrated into the chromosome. Replacement experiments revealed that the frequency of marker exchange and plasmid integration, respectively, lies in the same order of magnitude. The region of homology which is required for homologous recombination could at least be reduced to 200 bp. PMID- 7866723 TI - Functions of symbiotic fungus gardens in higher termites of the genus Macrotermes: evidence against the acquired enzyme hypothesis. AB - Behavioural, microbiological and biochemical studies on Macrotermes subhyalinus and M. michaelseni by collaborating laboratories in the U.K., Switzerland and Australia are described. Younger workers consume both primary forage and the conidia of a symbiotically associated fungus of the genus Termitomyces, but all workers produce a fully competent cellulase complex (endoglucanase + glucosidase) in the midgut which is clearly distinguishable from analogous enzymes in fungal tissues. Workers have a RQ of 1.0; although a bacterial flora is present, assessments of CH4/H2 efflux and intestinal VFAs suggest that respiration is sustained by aerobic carbohydrate dissimilation. Calculations based on estimates of food ingestion by workers and measurements of cellulase activity show that endogenous production of reducing sugars from polysaccharide is sufficient to sustain the observed metabolic rate. Conidia contain both cellulase and glucose at much higher concentrations than other fungal tissues, but the role and fate of these substances on entering the young worker guts is unknown. Older workers consume fully composted forage in which cellulose, hemicellulose, pectin and lignin are all significantly degraded, with a corresponding increase in nitrogen content. PMID- 7866724 TI - Characterization of turbot (Scophthalmus maximus) associated bacteria with inhibitory effects against the fish pathogen Vibrio anguillarum. AB - More than 400 isolates from the intestine and the external surface of farmed turbot, as well as from fish food and hatchery water were screened for inhibitory effects against the fish pathogen Vibrio anguillarum HI 11345 and seven other fish pathogens. The bacteria with inhibitory effects were then characterized with regards to their sites of colonization, especially the intestinal regions and sites within each region. No correlations between the different biochemical phena, site of colonization and inhibitory effect could be found. The potential of seven of these strains for adhesion to intestinal mucus from turbot was studied. Rapid growth of V. anguillarum in intestinal mucus was measured, hence it is feasible that the intestinal tract is a site for V. anguillarum multiplication. Strains isolated from the intestine showed greater capacity for in vitro adhesion to and growth in fish intestinal mucus than did the pathogen and skin mucus isolates. Two of the strains isolated from the intestine were studied for their inhibitory kinetics and one strain for the potential of in vivo colonization. The molecular weight of the inhibitory component was below 1000 dalton in 65% of the strains isolated. For the other 35% the inhibitory component ranged between 1000 D-6000 D in dialysis cut off experiments. One week after oral administration, one such isolate still accounted for 45% of the total c.f.u. in the intestinal mucus of 5 g turbot. In preliminary experiments we demonstrated that it is possible to detect the pathogen in intestinal mucus with a fluorescently labelled oligonucleotide probe directed against a specific part of the intracellular rRNA of V. anguillarum. PMID- 7866725 TI - Phenomenon of Rickettsiella phytoseiuli in Phytoseiulus persimilis mite. AB - An unknown microorganism occurring in a predaceous mite Phytoseiulus persimilis was described by the author in 1977 as a new species Rickettsiella phytoseiuli. Some new results on the relation between this agent and its hosts are presented in this paper. PMID- 7866726 TI - Penaeid prawns and associated luminous bacteria. AB - Luminous bacteria associated with the exoskeleton, gill and gut of penaeid prawns, Penaeus indicus H. Milne Edwards and Penaeus monodon Fabricius in Mangalore waters were isolated, identified and quantified. Two species of bacteria, Vibrio harveyi and Vibrio fischeri were recorded, the former was dominant in the exoskeleton and gill of both the penaeids. Gut of prawns supported exclusive and dense populations of V. harveyi suggesting that the species is well adapted to proliferate in this microenvironment especially in the hindgut region. PMID- 7866727 TI - Endotoxins and prednisolone alter replication of type 5 adenovirus and its temperature sensitive mutants. AB - Latency, replication or transformation by adenoviruses require cooperation between their gene products and cellular factors, which are controlled by external stimuli. Clinical observations suggest that bacterial endotoxin (LPS) and steroid hormones have direct effects on the viral permissivity and activation. Therefore, HEp-2 cultures were infected with low multiplicity of wild type (WT) human adenovirus 5 (Ad-5) and its temperature-sensitive mutants ts18 and ts19 damaged in the phosphorylation of structural polypeptides VI and X at 39 degrees C, respectively. Cultures were treated at permissive (32 degrees C) and nonpermissive (39 degrees C) temperatures with native and radio-detoxified (RD) LPS, alpha-tocopherol and prednisolone alone or in combination. Titration of virus yields showed dose-dependent activation and enhanced replication of latent WT and ts mutants by both LPS preparations. alpha-Tocopherol diminished these processes. LPS was likewise unable to augment virus producing capacity of cells. Prednisolone, although activating no latent virus, resulted in augmenting Ad-5 production at 32 degrees C. No compounds activated mutants at 39 degrees C except synergistic effect of LPS and prednisolone resulted in limited but significant replication of mutant ts19. Deliberation of lysosomal enzymes, enhanced cGMP and tumour necrosis factor alpha (TNF-alpha) productions by LPS as well as interaction of Ad early gene expression with prednisolone-utilized cellular transcription factors including AP-1 (c-jun, c-fos) are implicated in these processes. Excluding the role in activation of Ad proteinase processing viral structural polypeptides draws attention to the importance of cellular factors in virus replication. PMID- 7866728 TI - Cadmium mediated control of nitrogenase activity and other enzymes in a nitrogen fixing cyanobacterium. AB - Cadmium decreased the specific growth rate and total cell mass at concentrations > 0.001 micrograms ml-1. It also reduced heterocyst frequency, total cell protein, nitrogenase activity (acetylene reduction) and decreased glutamine synthetase (GS) and glutamate synthase (GOGAT) activities. However, cells grown under low concentration of cadmium (0.001 microgram ml-1) had enhanced nitrogenase as well as GS activity besides showing increased growth rate and heterocyst frequency. Cadmium has apparently controlled nitrogenase activity and nitrogen fixation possibly via mediating enzymes including glutamine synthetase in Nostoc muscorum. PMID- 7866729 TI - Soluble intercellular adhesion molecule-1 (sICAM-1) in Graves' disease. AB - The aim of this study was to determine the level of sICAM-1 in sera of hyperthyroid and euthyroid patients with Graves' disease and find correlation between thyroid function, anti-TSH receptor as well as anti-thyroid antibodies. Comparative determination of sICAM-1, TSH and thyroid hormones, anti-TSH receptor as well as anti-thyroglobin-, anti-thyroid peroxidase antibodies was made in sera of Graves' patients. Thirty patients with untreated hyperthyroid Graves' disease (12 had infiltrative ophthalmopathy) were studied before and after methimazole treatment. sICAM-1 was measured by ELISA using monoclonal antibodies to human ICAM-1. The sICAM-1 was significantly elevated in hyperthyroid Graves' patients (738.9 +/- 151 ng/ml) compared to controls (212 +/- 42 ng/ml) (p < 0.0001). Both in hyperthyroid and euthyroid Graves' groups with infiltrative ophthalmopathy the sICAM-1 proved to be higher than those without ophthalmopathy. Correlations were observed between sICAM-1 and serum thyroxine, triiodothyronine and anti-TSH receptor antibodies (r = 0.91, 0.83 and 0.61, respectively). There was, however, no association of serum ICAM-1 levels with anti-thyroid peroxidase or anti-thyroglobulin antibodies. It was concluded that elevation of sICAM-1 can be the consequence of hyperthyroidism and the autoimmune processes mediated by anti-TSH receptor antibodies as well as cytokines. The elevated level of sICAM-1 might be important both in regulation of autoimmune mechanism and "homing" phenomenon of lymphocytes in Graves' disease. PMID- 7866730 TI - The effect of X-radiation on reticulo-endothelial system and its treatment with radiodetoxified-endotoxin and trace elements in rats. AB - A new in vivo method has been developed for the precise observation of RES activity. Both Escherichia coli endotoxin 100 micrograms/100 g i.v. (LPS) and radiodetoxified endotoxin 100 micrograms/100 g body weight i.v. (RD-LPS, TOLERIN) both increased the granulopectic activity of RES. The RD-LPS was more effective. The preparation containing trace elements also increased the activity of RES. The treatment consisting of the use of both trace elements and RD-LPS proved to be the most effective. The activity of RES was inversely proportional to various doses of X-ray irradiation (7, 8, 9 Gy). Trace elements and RD-LPS even improved the immunity system of animals having deteriorated RES. PMID- 7866731 TI - Effect of radiodetoxified endotoxin and trace elements on reticulo-endothelial system damaged by ethanol in rats. AB - For the demonstration of RES activity 99-mTc labelled nano-albumon micro-colloid solution (prepared by OSSKI, Budapest, Hungary) was injected into the prepared jugular vein of narcotized rats and the clearance rate was investigated. The effects of various materials have been observed on RES in vivo. Continuous consumption of 20% ethanol solution for 15 weeks decreased the phagocytic activity. One hundred microgram/100 g body weight (i.v.) of the radio-detoxified endotoxin preparation (RD-LPS, TOLERIN) prepared from Escherichia coli endotoxin by 60Co-gamma irradiation (150 KGy) increased the granulopectic activity of RES of intoxicated animals. The preparation containing trace elements also increased the former activity and the treatment consisting of the use of both trace elements and RD-LPD was as effective as the RD-LPD per sc. PMID- 7866732 TI - Production of antibodies against adenovirus hexons in Escherichia coli by recombinant phages (a note). AB - For the study of complex antigen structures, such as the adenovirus hexon capsomer, monoclonal antibodies proved to be very useful tools. Production and stabilization of monoclonal antibodies in a larger amount is complicated and requires special infrastructural background, if we apply the convential hybridoma techniques. Recombinant DNA and gene amplification technology, however, has made it possible to clone antibody genes in bacteria, and to produce antibodies in bacterial cultures. PMID- 7866733 TI - Use of expandable stents for esophageal and biliary stenoses. PMID- 7866734 TI - Barrett's esophagus. AB - Barrett's esophagus is the condition wherein columnar epithelium replaces squamous epithelium in the esophagus. The condition is named for the late Mr Normal Barrett, an English surgeon whose most renowned publication, ironically, is a treatise contending that the esophagus cannot be lined by columnar epithelium. The eponym is used commonly despite Mr Barrett's mistaken contention, although some European authors still prefer to call the condition "endobrachyesophagus." Barrett's esophagus appears to be a sequela of gastroesophageal reflux disease (GERD), and it is the major known risk factor for esophageal adenocarcinoma. Barrett's esophagus is usually discovered during endoscopic evaluation of patients who have symptoms caused by GERD or esophageal cancer. Consequently, data on the clinical features of Barrett's esophagus are derived primarily from studies on symptomatic patients in whom the condition was recognized endoscopically. Recent investigations suggest that more than 90% of cases of Barrett's esophagus in the general population are not recognized by physicians, and many of these unrecognized patients have few or no symptoms of GERD. It is important to appreciate, therefore, that conclusions drawn from studies on patients with clinically apparent disease are not necessarily applicable to the "silent majority" of individuals with Barrett's esophagus. PMID- 7866735 TI - Celiac disease and the spectrum of gluten sensitivity. AB - Celiac disease is a well-known entity in which intolerance to wheat gluten and related proteins from barley, rye, and oats (collectively known as prolamins) damage intestinal mucosa. New insights into the pathology of the celiac intestinal lesion point to a wider spectrum of gluten sensitivity than previously thought. Recent advances in immunology and genetics have shed light on the underlying mechanisms and risks associated with the disease. Although the classical manifestations are well known, the wide variety of clinical presentations make celiac disease often difficult to diagnose, and the ubiquitous presence of prolamins in the Western diet make treatment challenging. PMID- 7866736 TI - Mesenteric venous thrombosis. AB - Mesenteric venous thrombosis (MVT) and its clinical expressions have become better defined as a result of improvements in both diagnostic imaging and our understanding of the various intestinal ischemic syndromes. Acute, subacute, and chronic forms of MVT are currently recognized, and these forms may differ in the symptoms they produce, the methods by which they are diagnosed, and the treatments they may require. Moreover, an underlying disease that predisposes a patient to MVT can be found in most instances. PMID- 7866737 TI - Pathogenesis, diagnosis, and treatment of diverticular disease of the colon. AB - Diverticular disease of the colon is a disease of twentieth century Western society. A diverticulum is an outpouching of mucosa through the colonic wall. Etiology and pathogenesis are related to altered colonic structure and physiology in an aging population. Epidemiological evidence suggests that a decrease in dietary fiber, as well as increasing age, lead to formation of diverticula. Diverticular disease includes pain without inflammation, diverticulitis, and bleeding. Severe diverticulitis is often complicated by abscess or fistula formation or peritonitis. Young obese men and immunocompromised patients have a more virulent course. Diverticular bleeding occurs as a result of a diverticulum eroding through a nutrient artery. Treatment of diverticular disease depends on severity and clinical presentation. A higher-fiber diet is recommended if there is no acute inflammation. Broad-spectrum antibiotics, diagnostic and therapeutic computed tomography scans, and early surgical intervention have improved the treatment of hospitalized patients with diverticular disease. The one-stage operation has increased in popularity for patients with localized disease because it reduces reoperative rates and hospitalization costs. Mortality remains high in patients with purulent and fecal peritonitis, and early recognition and treatment may benefit this subset of patients. PMID- 7866738 TI - Peptic ulcer disease in adolescence: changing concepts in the age of Helicobacter pylori. PMID- 7866739 TI - Irritable bowel syndrome. AB - Irritable bowel syndrome (IBS) is a common medical disorder that is associated with significant disability and health care costs. A practical approach to diagnosis and management of patients afflicted by this disorder has previously been hampered due to incomplete understanding of its pathophysiology, lack of diagnostic precision, and absence of specific treatments. Over the last decade, epidemiological, physiological, and psychosocial data have emerged to improve our understanding of this disorder and its treatment. IBS is currently believed to result from dysregulation of intestinal motor, sensory, and central nervous system function. Symptoms are due to both disturbances in intestinal motility and enhanced visceral sensitivity. Psychosocial factors, although not part of IBS per se, have an important role in modulating the illness experience and its clinical outcome. Use of multinational symptom-based "Rome" criteria has increased diagnostic specificity and has helped to minimize studies done to exclude other disease. Finally, treatment involves an integrated pharmacological and behavioral approach that is determined by the severity of the illness and its physiological and psychosocial determinants. PMID- 7866740 TI - Influenza haemagglutinin: illuminating fusion. PMID- 7866741 TI - Influenza hemagglutinin: kinetic control of protein function. AB - In response to decreased pH, influenza hemagglutinin changes to a more stable conformation. Such changes, which can be controlled thermodynamically or kinetically, are the method by which many biological 'switches' are thrown. PMID- 7866742 TI - Stereochemical dictionaries for protein structure refinement and model building. PMID- 7866743 TI - The structure of Pneumocystis carinii dihydrofolate reductase to 1.9 A resolution. AB - BACKGROUND: The fungal pathogen Pneumocystis carinii causes a pneumonia which is an opportunistic infection of AIDS patients. Current therapy includes the dihydrofolate reductase (DHFR) inhibitor trimethoprim which is selective but only a relatively weak inhibitor of the enzyme for P. carinii. Determination of the three-dimensional structure of the enzyme should form the basis for design of more potent and selective therapeutic agents for treatment of the disease. RESULTS: The structure of P. carinii DHFR in complex with reduced nicotinamide adenine dinucleotide phosphate and trimethoprim has accordingly been solved by X ray crystallography. The structure of the ternary complex has been refined at 1.86 A resolution (R = 0.181). A similar ternary complex with piritrexim (which is a tighter binding, but less selective inhibitor) has also been solved, as has the binary complex holoenzyme, both at 2.5 A resolution. CONCLUSIONS: These structures show how two drugs interact with a fungal DHFR. A comparison of the three-dimensional structure of this relatively large DHFR with bacterial or mammalian enzyme-inhibitor complexes determined previously highlights some additional secondary structure elements in this particular enzyme species. These comparisons provide further insight into the principles governing DHFR-inhibitor interaction, in which the volume of the active site appears to determine the strength of inhibitor binding. PMID- 7866744 TI - Structure of the photosynthetic reaction centre from Rhodobacter sphaeroides at 2.65 A resolution: cofactors and protein-cofactor interactions. AB - BACKGROUND: Photosynthetic reaction centres (RCs) catalyze light-driven electron, transport across photosynthetic membranes. The photosynthetic bacterium Rhodobacter, sphaeroides is often used for studies of RCs, and three groups have determined the structure of its reaction centre. There are discrepancies between these structures, however, and to resolve these we have determined the structure to higher resolution than before, using a new crystal form. RESULTS: The new structure provides a more detailed description of the Rb. sphaeroides RC, and allows us to compare it with the structure of the RC from Rhodopseudomonas viridis. We find no evidence to support most of the published differences in cofactor binding between the RCs from Rps. viridis and Rb. sphaeroides. Generally, the mode of cofactor binding is conserved, particularly along the electron transfer pathway. Substantial differences are only found at ring V of one bacteriochlorophyll of the 'special pair' and for the secondary quinone, QB. A water chain with a length of about 23 A including 14 water molecules extends from the QB to the cytoplasmic side of the RC. CONCLUSIONS: The cofactor arrangement and the mode of binding to the protein seem to be very similar among the non-sulphur bacterial photosynthetic RCs. The functional role of the displaced QB molecule, which might be present as quinol, rather than quinone, is not yet clear. The newly discovered water chain to the QB binding site suggests a pathway for the protonation of the secondary quinone QB. PMID- 7866745 TI - Crystal structure of scytalone dehydratase--a disease determinant of the rice pathogen, Magnaporthe grisea. AB - BACKGROUND: Rice blast is caused by the pathogenic fungus,-Magnaporthe grisea. Non-pathogenic mutants have been identified that lack enzymes in the biosynthetic pathway of dihydroxynapthalene-derived melanin. These enzymes are therefore prime targets for fungicides designed to control rice blast disease. One of the enzymes identified by genetic analysis as a disease determinant is scytalone dehydratase. RESULTS: The three-dimensional structure of scytalone dehydratase in complex with a competitive inhibitor has been determined at 2.9 A resolution. A novel fold, a cone-shaped alpha + beta barrel, is adopted by the monomer in this trimeric protein, burying the hydrophobic active site in its interior. The interactions of the inhibitor with the protein side chains have been identified. The similarity of the inhibitor to the substrate and the side chains involved in binding afford some insights into possible catalytic mechanisms. CONCLUSIONS: These results provide a first look into the structure and catalytic residues of a non-metal dehydratase, a large class of hitherto structurally uncharacterized enzymes. It is envisaged that a detailed structural description of scytalone dehydratase will assist in the design of new inhibitors for controlling rice blast disease. PMID- 7866746 TI - Stability and function: two constraints in the evolution of barstar and other proteins. AB - BACKGROUND: Barstar is the intracellular inhibitor of barnase, an extracellular RNAse of Bacillus amyloliquefaciens. The dissociation constant of the barnase barstar complex is 10(-14) M with an association rate constant between barnase and barstar of 3.7 x 10(8) s-1 M-1. The rapid association arises in part from the clustering of four acidic residues (Asp35, Asp39, Glu76 and Glu80) on the barnase binding surface of barstar. The negatively charged barnase-binding surface of barstar effectively 'steers' the inhibitor towards the positively charged active site of barnase. RESULTS: Mutating any one of the four acidic side chains of barstar to an alanine results in an approximately two-fold decrease in the association rate constant, while the dissociation rate constant increases from five orders of magnitude for Asp39-->Ala, to no significant change for Glu80- >Ala. The stability of barstar is increased by all four mutations, the increase ranging from 0.3 kcal mol-1 for Asp35-->Ala or Asp39-->Ala, to 2.1 kcal mol-1 for Glu80-->Ala. CONCLUSIONS: The evolutionary pressure on barstar for rapid binding of barnase is so strong that glutamate is preferred over alanine at position 80, even though it does not directly interact with barnase in the complex and significantly destabilizes the inhibitor structure. This, and other examples from the literature, suggest that proteins evolve primarily to optimize their function in vivo, with relatively little evolutionary pressure to increase stability above a certain threshold, thus allowing greater latitude in the evolution of enzyme activity. PMID- 7866747 TI - Conformational polymorphism of cyclosporin A. AB - BACKGROUND: Cyclosporin A (CsA) is a cyclic undecapeptide fungal metabolite with immunosuppressive properties, widely used in transplant surgery. It forms a tight complex with the ubiquitous 18 kDa cytosolic protein cyclophilin A (CypA). The conformation of CsA in this complex, as studied by NMR or X-ray crystallography, is very different from that of free CsA. Another, different conformation of CsA has been found in a complex with an antibody fragment (Fab). RESULTS: A detailed comparison of the conformations of experimentally determined structures of protein-bound CsA is presented. The X-ray and NMR structures of CsA-CypA complexes are similar. The Fab-bound conformation of CsA, as determined by X-ray crystallography, is significantly different from the cyclophilin-bound conformation. The protein-CsA interactions in both the Fab and CypA complexes involve five hydrogen bonds, and the buried CsA surface areas are 395 A2 and 300 A2, respectively. However, the CsA-protein interactions involve rather different side chain contacts in the two complexes. CONCLUSIONS: The structural results presented here are consistent with CypA recognizing and binding a population of CsA molecules which are in the required CypA-binding conformation. In contrast, the X-ray structures of the Fab complex with CsA suggest that in this case there is mutual adaptation of both receptor and ligand during complex formation. PMID- 7866748 TI - Mechanism of inhibition of 3 alpha, 20 beta-hydroxysteroid dehydrogenase by a licorice-derived steroidal inhibitor. AB - BACKGROUND: Bacterial 3 alpha, 20 beta-hydroxysteroid dehydrogenase (3 alpha, 20 beta-HSD) reversibly oxidizes the 3 alpha and 20 beta hydroxyl groups of androstanes and pregnanes and uses nicotinamide adenine dinucleotide as a cofactor. 3 alpha, 20 beta-HSD belongs to a family of short-chain dehydrogenases that has a highly conserved Tyr-X-X-X-Lys sequence. The family includes mammalian enzymes involved in hypertension, digestion, fertility and spermatogenesis. Several members of the enzyme family, including 3 alpha, 20 beta-HSD, are competitively inhibited by glycyrrhizic acid, a steroidal compound found in licorice, and its derivative, carbenoxolone, an anti-inflammatory glucocorticoid. RESULTS: The three-dimensional structure of the enzyme-carbenoxolone complex has been determined and refined at 2.2 A resolution to a crystallographic R-factor of 19.4%. The hemisuccinate side chain of carbenoxolone makes a hydrogen bond with the hydroxyl group of the conserved residue Tyr152 and occupies the position of the nicotinamide ring of the cofactor. The occupancies of the inhibitor in four independent catalytic sites refine to 100%, 95%, 54% and 36%. CONCLUSIONS: The steroid binds at the catalytic site in a mode much like the previously proposed mode of binding of the substrate cortisone. No bound cofactor molecules were found. The varying occupancy of steroid molecules observed in the four catalytic sites is either due to packing differences or indicates a cooperative effect among the four sites. The observed binding accounts for the inhibition of 3 alpha, 20 beta-HSD. PMID- 7866749 TI - Structure of the Escherichia coli signal transducing protein PII. AB - BACKGROUND: In Gram-negative proteobacteria, the nitrogen level in the cell is reflected by the uridylylation status of a key signal transducing protein, PII. PII modulates the activity of glutamine synthetase (GS) through its interaction with adenylyl transferase and it represses the expression of GS by acting in concert with nitrogen regulatory protein II. RESULTS: The three-dimensional structure of the Escherichia coli PII trimer has been determined at 2.7 A resolution. PII shows a low level of structural similarity to a broad family of alpha/beta proteins and contains a double beta alpha beta motif. The PII trimer contains three beta-sheets, each of which is composed of strands from each of the three monomers. These are surrounded by six alpha-helices. CONCLUSIONS: The structure of PII suggests potential regions of interaction with other proteins and serves as an initial step in understanding its signal transducing role in nitrogen regulation. PMID- 7866750 TI - [Outline of histomorphometric principles in pathomorphologic examination]. PMID- 7866751 TI - The effect of 1,2,3,4-tetrachlorodibenzo-p-dioxin on drug-metabolizing enzymes in the rat liver. AB - The effects of 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD) on drug metabolizing enzymes were studied in male and female rats. 1,2,3,4-TCDD (25, 50, 100 and 200 mumol/kg) was administered by i.p. injection once. Among the cytochrome P-450 (P450)-mediated monooxygenase activities tested, 7 ethoxyresorufin O-deethylase (EROD) activities in both male and female rats, which are associated with CYP1A1, were remarkably induced by all doses of 1,2,3,4 TCDD. The relative induction to each control activity were from 3.0- to 24.5-fold and from 2.2- to 16.5-fold, respectively. Also, 1,2,3,4-TCDD increased other CYP1A-mediated monooxygenase activities such as 7-ethoxycoumarin O-deethylase (ECOD) and 7-methoxyresorufin O-demethylase (MROD) in male and female rats dose dependently (1.4- to 4.3-fold). Western immunoblotting showed that the levels of CYP1A1 and CYP1A2 proteins in liver microsomes were increased by 1,2,3,4-TCDD. Although the activities of other P450-mediated monooxygenases, namely 7 pentoxyresorufin O-depentylase (PROD), 7-benzyloxyresorufin O-debenzylase (BROD), aminopyrine N-demethylase (APND) and nitrosodimethylamine N-demethylase (NDAND) in both male and female rats were induced at high doses (> or = 50 mumol/kg) of 1,2,3,4-TCDD, the relative level was low compared with those of the CYP1A mediated monooxygenase such as EROD, ECOD or MROD. In addition to P450-mediated monooxygenase, there was significant induction in the activities of the Phase II drug-metabolizing enzymes, UDP-glucuronyltransferase (UGT) activities towards 4 nitrophenol (4-NP) and 7-hydroxycoumarin (7-HC) and glutathione S-transferase (GST) towards 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB) and DT-diaphorase. These results indicate that 1,2,3,4-TCDD induces both Phase I (CYP1A-mediated monooxygenase) and Phase II drug-metabolizing enzymes (UGT, GST, DT-diaphorase) in the male and female rat liver, and that the alterations of drug-metabolizing enzyme are characteristic of PCDD toxicity. PMID- 7866752 TI - Characterization of the humic material formed by composting of domestic and industrial biowastes. Part 1. HPLC of the cupric oxide oxidation products from humic acids. AB - The changes induced by humification of anaerobically digested sewage sludge, source separated biowaste, and pulp mill biosludge were determined by extracting the fractions of bitumen and humic and fulvic acids from the samples of fresh and humified composts. In all cases, a distinct decrease in the amount of bitumen could be detected during humification. The amount of humic acids increased in sewage sludge and biowaste samples, but decreased in pulp mill biosludge sample during humification. The humic acids were degraded by CuO oxidation and the phenolic degradation products were analysed by reversed-phase high-performance liquid chromatography. The yield of these aromatic degradation products was in the range 0.9-2.0% for each sample. The main phenolic degradation products were 4 hydroxybenzoic acid, vanillic acid, 4-hydroxybenzaldehyde, vanillin, syringaldehyde, and acetovanillone. Two lignin dimers, dehydrodivanillin and dehydrodiacetovanillone, were also identified. PMID- 7866753 TI - Staging, grading and related histopathological techniques in local therapy of rectal tumours. AB - Today, local therapy is an established alternative to radical resection for the treatment of rectal tumours. Selection of the operative technique requires an exact perioperative estimation of risks, with both clinical and histopathological examination. Of crucial importance in making a decision to perform a local resection is exact and meticulous histopathological preparation of the tissue. The most important criterion is the estimation of risk of lymph node metastases. This risk is assessed on the basis of the depth of invasion of the tumour, the histological grade of differentiation and the presence or absence of invasion of lymphatic vessels. PMID- 7866754 TI - Indications and technique for TEM (transanal endoscopic microsurgery). AB - Transanal Endoscopic Microsurgery (TEM) was introduced into clinical practice by the Buess group in 1983. Since then vast experience has been gained in removing tumours of the rectum by the operative rectoscope. Though the indication in benign lesions for TEM as a local resection therapy is undisputed, the indication for resection of T1 or advanced carcinomas has to be evaluated. By using a 40 mm operating rectoscope sealed with a gastight working insert to prevent pressure loss after creation of a pneumorectum and a stereoscopic optic with sixfold magnification, exact visualisation of a rectal tumour can be achieved. The insertion of endoscopic surgical instruments like the high frequency knife, forceps, scissors, and suction device allows precise excision of the lesion as well as suture closure of the wound. Recently a bipolar multifunctional combination instrument has been developed for more precise dissection, less blood loss and shorter operation times. PMID- 7866755 TI - TEM results of the Tuebingen group. AB - From August 1st 1989 to May 1st 1993, 190 rectal adenomas and 75 carcinomas were locally excised with the TEM technique. The mortality was 0.4%, the rate of complications which required surgical re-intervention was 3% in adenomas and 8% in carcinomas. The final histology of the removed carcinomas revealed 44 pT1, 23 pT2 and eight pT3 stages. In two of the eight re-resected patients with pT1 low risk tumours, residual primary tumour but no lymph node metastases were found. In contrast to this, three of the eleven re-resected patients with pT2 low-risk tumours had already developed lymph node metastases. After an average follow-up time of 14 months, two recurrences were observed in the group of the only locally treated patients with pT1 low-risk carcinomas. Both underwent a secondary procedure for cure but in late tumour stages. No recurrence was diagnosed so far among the re-resected patients. PMID- 7866756 TI - Experience with TEM in Germany. AB - Transanal endoscopic microsurgery (TEM) presents a minimally invasive procedure for local removal of large adenomas as well as early carcinomas of the rectum. 57 surgical departments/clinics, which practice this method in Germany were asked about their experience. 44 questionnaires were evaluated. Indications for the 1,900 recorded operations were 1,411 adenomas, 433 carcinomas (curative intention: 286; palliative intention: 147), and 56 other procedures. The conversion rate to laparotomy was dependent on the experience with this surgical method (1.2%-11.6%). A radical rectal resection as a second step was performed in 5.7% of patients in the case of advanced carcinoma in the histologic examination of the specimen. Complications appeared in 120 patients (6.3%), 77 patients (4.0%) recovered with conservative treatment, and 43 (2.3%) had to undergo surgery. The mortality rate was 0.2% (3/1,900 pts). PMID- 7866757 TI - Transanal endoscopic microsurgery in Italy. AB - The Italian experience with Transanal Endoscopic Microsurgery (TEM) started in 1991. Until April, 1994, 122 patients were operated on by such a technique in six centres. The surgical protocol in the 66 patients with benign lesions was similar to that described by Buess. In contrast to the German experience, the indications of TEM for cancer have been extended to more advanced tumours and in 22 out of 56 patients with rectal carcinoma adjuvant radiation- or radiation-chemotherapy have been applied according to various protocols. In 88% of TEM for rectal tumours the operation has been carried out according to a full-thickness technique, with or without perirectal fat excision. Postoperative morbidity of TEM for adenoma was 15.8% and that of TEM for carcinoma 29.6%. There was no postoperative mortality. Local recurrence rate after TEM for adenoma was 10.5%, while that after TEM for cancer was 9.25%. No local recurrence has been reported among patients treated with a combination of TEM and adjuvant radiation treatments. The median follow-up in the 6 centres ranged between 7 and 16 months. A randomised prospective clinical trial has been planned in order to evaluate the role of transanal endoscopic microsurgery in the treatment of locally advanced rectal cancer. PMID- 7866758 TI - Transanal endoscopic anorectal mucosectomy with ileal pouch anal anastomosis for familial adenomatous polyposis. A case report. AB - In patients with familial adenomatous polyposis (FAP) who are undergoing ileal pouch-anal anastomosis (IPAA), transanal mucosectomy can be performed without excessive anal dilatation and manipulation using the operative proctoscope introduced by Buess. In this way, mucosectomy under a direct three-dimensional six-fold magnified view is accurate and bloodless. PMID- 7866759 TI - A preliminary report on endoscopic transanal resection of the rectum. AB - Since 1986 we have performed 62 endoscopic transanal resections (TAR) on 43 patients with malignant or benign tumours. Initially a transurethral resectoscope was used, and later the recently developed rectal resectoscope was introduced, enabling diathermy resection of a rectal lesion growing into the lumen of the rectum and making it possible to take the resection level up to or below the level of the muscularis propria. The wound is left to epithelialise spontaneously. 32 patients with malignant lesions of the rectum underwent TAR. The aim was to palliate symptoms and avoid colostomy. 11 patients with benign tumours (8 adenomas, 2 polyps, 1 stricture) also underwent TAR. No patient died within 25 days of operation. TAR is a minimally invasive procedure. It is quick, safe and effective if performed caudal to the peritoneal reflection fold. PMID- 7866760 TI - Technique and results using the glass-rectoscope for tumour resection. AB - The glass-rectoscope, developed by P. Dewey is a cylinder speculum with a closed end and a working window at the side. This is a cheap instrument and method for transanal approach to the lower rectum. After preparation of the patient by saline lavage the day before operation and one dose antibiotic preoperatively, the operation is performed under general or epidural anesthesia. The digital slow dilatation of the anal sphincter is followed by introduction of the instrument, of which several versions are available. After focusing the lesion in the working window, diathermy-excision of the mucosa or of the total rectal wall is performed. Bleeding is controlled by electrocoagulation or by continuous suture of the resulting defect in the rectal wall. In 34 patients treated by transanal tumour resection, there was one local infection and four postoperative haemorrhages required operative revision by resuture. The method is suitable for removing lesions of the lower rectum up to the diameter of 2 cm and for stage T1N0 malignant lesions. PMID- 7866761 TI - Estimated worldwide total of surgeons using minimally invasive surgery (MIS). PMID- 7866762 TI - Processing of instruments for endoscopic surgery. PMID- 7866763 TI - Preparation of instruments used in minimally invasive surgery in a washer disinfector. AB - The safe sterilisation of surgical instruments presumes that one is dealing with small amounts of standardised residual contamination and in particular, that the cleaning process adheres to good manufacturing practices, taking into account the protection of the personnel. Only mechanical processes can be standardised and are suitable for the preparation of surgical instruments. The development process which the instruments used in minimally invasive surgery have undergone, along with improvements in the field of cleaning technology and disinfection, now means that preparation of instruments of this nature can be entrusted to an automatic washer/disinfector. New cleaning and disinfection methods allow the complete array of instruments, including fibreoptic light guides and lenses, to be cleaned and disinfected in one procedure. PMID- 7866764 TI - New sterilisation technologies--are they applicable for endoscopic surgical instruments? AB - It has been well established that instruments for minimally invasive surgery (MIS) must be treated like ordinary surgical instruments when they are intended for use within sterile areas of the human body. Due to the special design of most MIS instruments autoclaving (i.e. application of heat) may damage these delicate items. Therefore, low temperature sterilisation processes are essential. Gas sterilisation with ethylene oxide and formaldehyde may pose significant health hazards to workers exposed to these gases and to patients due to residues remaining on the surface of the instruments. Their general use in hospitals is more and more discouraged. However, with the advent of hydrogen peroxide gas plasma sterilisation there is a true alternative available for the sterilisation of MIS instruments. In contrast, the use of immersion sterilants such as liquid glutaraldehyde or peracetic acid cannot be considered as adequate because it is almost impossible to keep the processed instruments sterile until their intended use. PMID- 7866765 TI - Automated processing of endoscopic surgical instruments. AB - This paper deals with the requirements for automated processing of endoscopic surgical instruments. After a brief analysis of the current problems, solutions are discussed. Test-procedures have been developed to validate the automated processing, so that the cleaning results are guaranteed and reproducable. Also a device for testing and cleaning was designed together with Netzsch Newamatic and PCI, called TC-MIC, to automate processing and reduce manual work. PMID- 7866766 TI - Processing of surgical instruments for minimally invasive surgery. AB - Processing of surgical instruments for Minimally Invasive Surgery (MIS). General information on the development of Minimally Invasive Surgery and MIS instruments is given. The "MIS" scientific study group was formed to discuss and find solutions for design and hygienic problems in MIS. The article describes various groups of MIS instruments, i.e. disposable instruments, instruments with a cleaning channel, and instruments which can be dismantled. Aspects of how the instruments can be processed effectively will be discussed in detail, including an example of a survey carried out in a German hospital with a special monitoring method. Requirements are described for MIS instrumentation with regard to design, material, and surface conditions. Requirements for hygienic processing methods are listed. The article also describes the necessary control and confirmation of cleanliness, which proves to be a very particular problem. Conclusions on the present status of technology and the possibilities for future development with regard to the processing of MIS-instrumentation are given. PMID- 7866767 TI - Manatee cerebral cortex: cytoarchitecture of the caudal region in Trichechus manatus latirostris. AB - In several brains of the Florida manatee, Trichechus manatus latirostris, the architecture of caudal regions of cerebral cortex was examined in order to complete a map of cortical areas in the brain of this unique herbivore. Through observation of sections stained for Nissl substance, myelinated axons, acetylcholinesterase and cytochrome oxidase, we have identified 11 new cortical areas based on qualitative cytoarchitectural appearance and measurements of laminar thicknesses, for a total of 24 such cortical areas in manatee cerebral cortex. Some areas exhibit poorly differentiated laminae while in others there are 6 clearly demarcated layers, often with sublaminar organization. Some previously identified areas were found to extend into the region caudal to the vertically oriented lateral fissure. As in other mammalian brains, cortical areas in manatees are organized in concentric rings of allocortex, mesocortex, and isocortex. Putative functional roles have been assigned to most of the identified areas based on location, architecture, behavioral and anatomical considerations, and extrapolation from other taxa in which functional mapping has been done. PMID- 7866768 TI - The morphology of the olfactory epithelium in larval, juvenile and upstream migrant stages of the sea lamprey, Petromyzon marinus. AB - The structure of the olfactory epithelium in the larval, juvenile and upstream migrant stages of the sea lamprey, Petromyzon marinus, was investigated by light microscopy and by scanning and transmission electron microscopy. Ciliated olfactory receptor cells (ORC) were present in all stages. In larval specimens, the number of ORC was 20 +/- 8 ORC per 100 microns length of olfactory epithelial surface. In juveniles and in upstream migrants the ORC density dropped to 9 +/- 2 and 6 +/- 2 ORC/100 microns, respectively. Sustentacular cells were microvillar in the smallest larval stage (with a body length of 15 mm) and ciliated in larger larvae and later life stages. The morphological characteristics of the olfactory mucosa suggest that the sea lamprey's capacity for use of the olfactory system extends into the larval stage, and that there are specific changes associated with metamorphosis. PMID- 7866769 TI - Visual resolution during growth in a cichlid fish: a morphological and behavioural case study. AB - The spatial resolution of the visual system during growth of the cichlid fish Haplochromis argens was deduced from the cone density according to two models of possible connectivity patterns. The models include a convergency type of 5 cones per visual unit and a divergency type of 1.25 cones per visual unit. The minimum separable angle in this species was measured during ontogeny using operant conditioning in a two choice discrete trial situation. As a consequence of the moderate performances of the juveniles, the behavioural study showed a greater change of visual resolution than was predicted by the morphology. The minimum separable angle of the adult fishes was accurately predicted by the 'divergency model', which led to rejection of the other morphological model. It is argued that the high resolution as found in some other fish species by authors using the same technique may be due to imperfect calculations. PMID- 7866770 TI - The visual system of the Florida garfish, Lepisosteus platyrhincus (Ginglymodi). IV. Bilateral projections and the binocular visual field. AB - Infusion of cobaltous-lysine into the optic nerve of juvenile Florida garfish reveals that the preoptic area, pretectum, thalamus and the mediorostral and ventrolateral poles of the optic tectum each receive bilateral, monosynaptic input. The bilateral input to the mediorostral pole of the tectum projects via the dorsal optic tract and terminates in the rostral half of the tectum. The bilateral input to the ventrolateral tectum projects via the ventral optic tract and extends the whole length of the tectum. The incidence of direct ipsilateral input to the tectum suggests binocular vision may play a functional role in the survival of this species. In order to test this hypothesis, we examined the retinal distribution of ipsilateral retinal ganglion cells that project to the mediorostral tectum and the size and location of the binocular visual field. Cell distribution was examined by retrograde labelling with rhodamine-conjugated dextran amine delivered by microinjections into the mediorostral pole of the right optic tectum. In the ipsilateral retina, ganglion cells are distributed in a narrow temporoventral area with a mean of 0.44 +/- 0.14 x 10(3) cells per mm2 apposing the retinal margin. In the contralateral retina, ganglion cells are also distributed within this temporoventral region with a mean peak density of 2.33 +/ 0.47 x 10(3) cells per mm2. Three broad classes of ipsilaterally projecting retinal ganglion cells (orthotopic cells within the ganglion cell layer, displaced cells within the inner nuclear layer, and giant cells within the ganglion and inner nuclear layers) are identified, intermingled in both the ipsilateral and contralateral retinae after retrograde labelling from the mediorostral pole of the tectum. Ophthalmoscopic mapping of the monocular and binocular visual fields reveals two small frontal wedges of binocular overlap. A dorsal wedge (12 degrees wide) extends from approximately 7 degrees above the horizontal axis to 10 degrees beyond the vertical axis, and a ventral wedge (20 degrees wide) extends approximately 10 degrees below the horizontal axis to 15 degrees beyond the vertical axis. The dorsal binocular visual field is subtended by the temporoventral region of the retina possessing both ipsilaterally and contralaterally projecting ganglion cells which terminate in the mediorostral pole of the optic tectum. Therefore, the partial decussation of retinal ganglion cell axons at the optic chiasm brings information from corresponding regions of the binocular visual field into register in the mediorostral pole of the optic tectum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866771 TI - Hippocampal volume and food-storing behavior are related in parids. AB - The size of the hippocampus has been previously shown to reflect species differences and sex differences in reliance on spatial memory to locate ecologically important resources, such as food and mates. Black-capped chickadees (Parus atricapillus) cached more food than did either Mexican chickadees (P. sclateri) or bridled titmice (P. wollweberi) in two tests of food storing, one conducted in an aviary and another in smaller home cages. Black-capped chickadees were also found to have a larger hippocampus, relative to the size of the telencephalon, than the other two species. Differences in the frequency of food storing behavior among the three species have probably produced differences in the use of hippocampus-dependent memory and spatial information processing to recover stored food, resulting in graded selection for size of the hippocampus. PMID- 7866772 TI - Age-related changes of AMP breakdown in chicken heart. AB - The activity of adenylate deaminase, adenylate phosphatase and adenosine deaminase, as well as the endogenous content of adenine nucleotides, was examined in the heart of ageing chickens. In new-born (1-day-old) and young (20-day-old) chickens, AMP degradation in the heart seems to proceed preferentially through deamination, while in adult (1-year-old) through dephosphorylation. Compared with the adult heart, a 2-year-old one exhibits a decline of AMP catabolism. The total adenine nucleotide content and the concentration of ATP are higher in adult and aged chicken hearts, than in new-born and young ones. Adaptive mechanisms might occur in the heart of ageing chickens to ensure an adequate availability of adenine nucleotides. PMID- 7866773 TI - Comparison of antibacterial activity in the hemocytes of different crustacean species. AB - Antibacterial activity in hemocytes of the squat lobster, Galathea strigosa, the Norway lobster, Nephrops norvegicus, the common shrimp, Crangon crangon, and the giant Antarctic isopod, Glyptonotus antarcticus, was investigated in vitro. For all species, the marine bacterium, Psychrobacter immobilis, was used as the test organism, although with G. antarcticus, the Gram positive bacteria, Planococcus citreus and BS 68 (an isolate from Antarctic waters), were also used. Hemocyte lysate supernatants (HLS) from all four species reduced the viable count of test bacteria over a period of 4 hr showing that their hemocytes contain factors able to neutralize bacteria in vitro. However, comparison of responses produced by serially diluted samples of HLS from G. strigosa, N. norvegicus and C. crangon, revealed that activity (per unit protein) is weaker than for Carcinus maenas. Using G. antarcticus, positive activity was also observed against P. citreus and BS 68; with the response effective against all of the bacteria at both 0 degree C and 20 degrees C. These results show that: (1) the hemocytes from a range of crustacean species contain factor(s) able to neutralize bacteria in vitro; (2) antibacterial potency varies from species to species; and (3) antibacterial immunity in at least one polar invertebrate functions at low temperature. PMID- 7866774 TI - Chronic intravenous infusion of chicken growth hormone increases body fat content of young broiler chickens. AB - The purpose of this study was to determine the effects of programmed intravenous infusion of chicken growth hormone (cGH) on growth and metabolism of young broiler chickens (4-7 weeks of age). Four-week-old broiler cockerels, fitted with indwelling jugular catheters, were randomly assigned to three treatment groups (6 birds/group): pulsatile infusion of buffer (phosphate buffer, pH 7.4)[PB-P] at 3 hr intervals, pulsatile infusion of cGH (15 micrograms/kg at 3 hr intervals)[GH P], or continuous infusion of cGH (120 micrograms/kg-day)[GH-C]. Birds were bled 5 min before (0-min) and 5 min post-infusion (relative to the pulses of PB and cGH) at 5, 6, and 7 weeks of age. Pulsatile infusion of cGH increased (P < 0.05) feed consumption by 24% and reduced (P < 0.05) feed efficiency by 14% without affecting body weight (BW) gain. The relative weights (%BW) of liver, abdominal fat, and bursa of Fabricius were not affected by the pattern of cGH infusion. However, the body fat content of cGH-infused chickens was increased (P < 0.05) by 13% (GH-C) and 17% (GH-P), while body protein and water contents were slightly reduced. Body ash content was not affected by pattern of cGH infusion. When compared with the PB-P controls, the GH-P treatment depressed (P < 0.05) hepatic GH-binding activity by 52% without affecting plasma insulin-like growth factor-I (IGF-I) levels. Continuous infusion of cGH increased (P < 0.05) plasma IGF-I by 16%, thyroxine (T4) by 31%, and glucagon levels by 55%, although plasma GH levels were only 47% higher than those of the PB-P group. However, the GH-P treatment was only half as effective as the GH-C pattern in elevating plasma levels of T4 and glucagon. This study shows that programmed intravenous infusion of cGH increases deposition of body fat in young rapidly-growing broiler chickens. PMID- 7866775 TI - Delayed inhibition of gap-junctional intercellular communication in the acinar cells of rat submandibular glands induced by parasympathectomy and cholinergic agonists. AB - In this study, the effects of parasympathectomy and cholinergic agonists on gap junctional intercellular communication and salivary secretion were investigated to clarify the involvement of salivary secretion in delayed uncoupling between acinar cells of rat submandibular glands. Gap-junctional intercellular communication was monitored as dye-coupling in the acinar cells of isolated acini by the transfer of Lucifer Yellow CH. Parasympathectomy induced dye-uncoupling in the acinar cells isolated from denervated salivary glands 12 hr after parasympathectomy-induced salivary secretion. Intraperitoneal application of carbachol (CCh), acetylcholine, pilocarpine, but not isoproterenol, stimulated salivary secretion, and then induced dye-uncoupling in the acinar cells 12 hr later. Atropine suppressed both the salivary secretion and delayed dye-uncoupling induced by parasympathectomy and CCh, when atropine was applied intraperitoneally before the induction of salivary secretion. However, atropine did not suppress the delayed dye-uncoupling by intraperitoneal application of CCh, when atropine was injected after the cessation of CCh-induced secretion. These results suggest that delayed inhibition of gap-junctional intercellular communication by parasympathectomy and cholinergic agonists in rat submandibular glands might be related to the change of secretory function after salivary secretion. PMID- 7866776 TI - The thermal biology of the white-tailed rat Mystromys albicaudatus, a cricetine relic in southern temperate African grassland. AB - This study examines the hypothesis that Mystromys albicaudatus, a cricetine relic in southern Africa, has thermal characteristics typical of a rodent adapted to a cold temperature regime. Metabolic rate (oxygen consumption) of M. albicaudatus was measured using open-flow respirometry at ambient temperatures ranging from 5 degrees C to 35 degrees C. Lowest specific oxygen consumption was 1.352 +/- 0.089 ml O2 g-1hr-1 (n = 8; body mass = 93.78 +/- 6.27 g) at 25 degrees C, equivalent to 121.8% of the predicted value of Kleiber (1975), 128.8% of the value predicted for eutherians and 113.7% of the value predicted for cricetidae (Hayssen and Lacy, 1985). PMID- 7866777 TI - Distribution of arginine-vasopressin in the trigeminal, dorsal root ganglia and spinal cord of the rat; depletion by capsaicin. AB - We have measured arginine vasopressin in the neural lobe, the trigeminal ganglion (TG), dorsal root ganglia (DRG), spinal cord, trigeminal and sciatic nerves of the rat by radioimmunoassay. In control rats, the neural lobe contained 1600 pg/mg, the ganglia 52.5, 21.0, 8.5, 4.28, 3.85 pg/mg in the lumbar, sacral, cervical, thoracic, and trigeminal ganglion, respectively, the spinal cord contained 5.1, 4.3, 4.2 and 2.6 pg/mg in the lumbar, thoracic, sacral and cervical cord, respectively and the trigeminal and sciatic nerves contained 3.8 and 13 pg/mg. Neonatal capsaicin treatment depleted about 38-67% of AVP in the ganglia. Residual AVP amounted to 526.8, 30.55, 20.75, 12.88, 4.95, 2.74, 2.14, 7.94 and 2.53 pg/mg in the neural lobe, lumbar, thoracic, sacral, cervical DRG, lumbar, thoracic spinal cord, the sciatic and trigeminal nerves respectively. Capsaicin destroyed about 40.5% of total cells and 52% of AVP-immunoreactive neurons. PMID- 7866778 TI - Adenylate cyclase activity from Hirudo medicinalis segmental ganglia: modulation by calcium and calmodulin. AB - An adenylate cyclase activity stimulated by serotonin and calmodulin is present in the segmental ganglia of the leech Hirudo medicinalis. Removal of the endogenous calcium binding protein does not alter the responsiveness of the enzyme to serotonin. The calmodulin antagonist, trifluoperazine, drastically reduces the amine stimulatory effect on both intact and calmodulin-depleted membranes. We suggest that calmodulin-sensitive and serotonin-stimulated adenylate cyclase are, at least functionally, independent. PMID- 7866779 TI - Cross reactivity studies of CRF-related peptides on insect Malpighian tubules. AB - Manduca sexta diuretic peptide II (Mas-DPII) stimulates fluid secretion by adult Malpighian tubules and cyclic AMP production by larval proximal and adult tubules of M. sexta in a dose-dependent manner. Mas-DPII has no effect on fluid transport across the larval cryptonephric complex. M. sexta diuretic hormone (Mas-DH) and CRF-related insect diuretic peptides from Acheta domesticus, Locusta migratoria, and Periplaneta americana also cause similar increases in the production of cyclic AMP by the Malpighian tubules of both larval and adult M. sexta. Insect CRF-related diuretic peptides exhibit varying degrees of potency when assayed on Malpighian tubules from L. migratoria and A. domesticus. Sauvagine, bovine-CRF, and human-CRF have only a small, but significant, effect on cyclic AMP production by M. sexta Malpighian tubules. However, sauvagine, bovine-CRF, and sucker fish urotensin-I have no effect on L. migratoria tubules. Stimulation of cyclic AMP production by M. sexta Malpighian tubules could potentially be used as a screening assay to identify other insect CRF-related diuretic peptides. PMID- 7866781 TI - Obtaining a BSN degree through an external degree program. PMID- 7866780 TI - Across the world ... notes from China. Part I. PMID- 7866782 TI - LTC law: the Americans with Disabilities Act: will it change the way you select nursing personnel? PMID- 7866783 TI - A country day. PMID- 7866784 TI - A different kind of caring! PMID- 7866785 TI - Who makes policy decisions for long term care nursing? PMID- 7866786 TI - Tuberculosis-implications for long term care: CDC guidelines & OSHA enforcement. PMID- 7866787 TI - Using standard definitions of infection. PMID- 7866788 TI - LTC law: staff nurses classified as supervisors by the United States Supreme Court. PMID- 7866790 TI - External degree nursing programs: do they represent a valid educational alternative for the adult learner. PMID- 7866789 TI - The right to self-determination. How Arkansas health care institutions assure that right. PMID- 7866791 TI - Leadership styles. PMID- 7866792 TI - Across the world ... notes from China. Part II. PMID- 7866793 TI - AIDS and long term care: update from the 10th international AIDS conference. PMID- 7866794 TI - Nursing home industry gets first prize for most staff injuries. What does this tell us? PMID- 7866795 TI - Not in the books... PMID- 7866796 TI - The effect of added extra-articular procedure on results of ACL reconstruction. AB - To determine the efficacy of added extraarticular backup procedure to an intra articular ligament reconstruction, 70 patients who underwent surgery between July 1988 and May 1991 were reviewed retrospectively. Each patient had undergone either an intra-articular patellar tendon autograft anterior cruciate ligament (ACL) reconstruction alone or with added extra-articular augmentation. Patients were excluded if they had a history of knee problems, if they had ACL surgeries on either knee, or if they became unavailable for followup for an adequate period of time. Thirty-two patients underwent ACL reconstruction with an extra-articular augmentation added (group 1), and 38 patients underwent intra-articular reconstruction alone (group 2). Objective testing consisted of a clinical examination, radiographs, instrumented knee laxity, and subjective evaluation using visual analog scales. There were no statistically significant differences in the clinical or subjective findings between the two groups. PMID- 7866797 TI - Combined single-strand distal semitendinosus-iliotibial band tenodesis (Puddu) for anterior cruciate ligament augmentation. AB - Anterior cruciate ligament (ACL) reconstruction using the semitendinosus tendon has seen renewed interest recently. Puddu described a procedure in which the tendon is harvested at its insertion on the tibia with a bone plug. This study evaluates the efficacy of this approach and examines the long-term results. Between 1982 and 1986, 77 patients underwent this type of procedure; 51 (66%) patients who were reexamined comprised the study group. Thirty-five patients had acute tears, and 16 patients had chronic tears. Follow-up was both objective and subjective with an average follow-up of 7 years and 3 months (range: 5.8 to 9.2 years). In the acute group, six patients (17%) had a 2+ Lachman and seven (22%) had a 1+ Lachman. Pivot shift was 2+ to 3+ in three patients (8.6%) and 1+ in seven patients (22%). KT-100 results were > 5 mm in eight patients (23.3%). In the chronic group, four patients (25%) had 2+ and four had a 1+ Lachman. Seven patients (44%) had a positive pivot shift test. Five patients had > 5 mm difference. Using regression analysis, the KT-1000 results correlated well with the Lachman and pivot shift tests. Chronicity and partial meniscectomy were associated with a poor result. Although this technique has undergone an evolution and improvement to a four-strand reconstruction in recent years, the results of this review indicate satisfactory results can be obtained, especially in the acute setting. PMID- 7866798 TI - Robotrac in total knee arthroplasty. The silent assistant. AB - This article describes a new prerobotic device (Robotrac) that may be used effectively in total knee arthroplasty (TKA). This device holds the femur in any position, allowing the surgeon to situate the knee in any position of flexion that may be necessary during the course of TKA. Using this device, it often is possible to perform TKA without any additional assistant surgeons. To date, we have used Robotrac in more than 200 consecutive total knee replacements without any untoward effects. With the use of this device, it is possible to save about $142 Canadian per total knee replacement. The literature concerning the use of robotics in medicine is reviewed. PMID- 7866799 TI - Effect of ketorolac tromethamine (Toradol) on ecchymosis following anterior cruciate ligament reconstruction. AB - This article describes a study that assesses whether patients who received ketorolac tromethamine (Toradol; Syntex Research, Palo Alto, California) during knee surgery had an increased tendency to develop ecchymosis in the lower limb versus patients who did not receive ketorolac tromethamine. Sixty-four patients who underwent anterior cruciate ligament (ACL) surgery were divided randomly into three groups: patients who received Toradol at tourniquet inflation (TorTourn) at the end of surgery (TorEnd), or not at all (TorNone). None of the patients exhibited abnormal preoperative bleeding times. One week postsurgery, patients were evaluated photographically for ecchymosis between the hip and malleoli of the surgical limb. Ecchymotic areas between the hip and malleoli were traced around their borders with a black marker. Three photographs of each surgical knee were taken: posterior, anterolateral, and anteromedial views. Each patient's photos then were scanned into a computer and the amount of encircled (ecchymotic) surface area and the total surface area of the limb were calculated. For each view, the ecchymotic surface area was divided by the total surface area to obtain a percentage of ecchymosis on that view. The percentages for the three views were added to obtain a single score for each patient. The mean ecchymotic surface area score was 21.9 +/- 31% for the TorTourn group, 27.5 +/- 25.5% for the TorEnd group, and 30.3 +/- 36.4% for the TorNone group. There was no significant difference in the ecchymotic surface area among the groups. This study suggests that ketorolac tromethamine does not affect the amount of ecchymosis that occurs following knee surgery. PMID- 7866801 TI - Midsubstance anterior cruciate ligament rupture in a 7-year-old child. Case report. PMID- 7866800 TI - The use of the Cryo/Cuff versus ice and elastic wrap in the postoperative care of knee arthroscopy patients. AB - Pain and swelling, which may lead to inhibition of the extensor mechanism and ultimately a delay in rehabilitation, are common complications of knee arthroscopy. Cryotherapy is the most often used means of decreasing both knee edema and discomfort. A number of methods have been used to provide cold pressure dressings, including ice and elastic bandages. Commercial devices, such as the Cryo/Cuff, also have been developed to provide similar beneficial effects. This article describes a multicenter randomized study undertaken to determine whether the Cryo/Cuff or the ice and elastic bandage offers the greatest convenience and relief of pain. One hundred two patients between the ages of 18 and 65 scheduled to undergo knee arthroscopy were enrolled. Postoperatively, the Cryo/Cuff patients required significantly less pain medication than those patients using the ice and elastic wrap. The Cryo/Cuff patients also expressed a high level of satisfaction with the effectiveness and convenience of the therapy. There were no differences between either group in the amount of pain reported, or preoperative and postoperative examinations in regard to knee range of motion and thigh circumference. These results indicate that the Cryo/Cuff is a useful adjunct in the rehabilitation of knee arthroscopy patients. PMID- 7866802 TI - Mycobacterium avium-intracellulare infection of the knee joint. Case report. AB - A 57-year-old white male with a history of scleroderma developed an osteoarticular infection of the right knee caused by Mycobacterium avium intracellulare. The patient underwent arthroscopic synovectomy and was started on appropriate combination chemotherapy. The patient failed to improve clinically and developed osteomyelitis of the patella, distal femur, and proximal tibia. The patient refused further surgical intervention and subsequently developed a "Charcot-like" knee joint. This case report documents the failure of medical treatment alone for this infection, which must be combined with aggressive surgical intervention. PMID- 7866803 TI - Tibial intramedullary alignment in total knee arthroplasty. AB - This article describes a study that assessed the accuracy of a tibial intramedullary alignment device in 44 adult cadaveric tibiae. The results suggest that greater accuracy is achieved if the device is inserted fully to the level of the distal epiphyseal scar and if used in the nonvalgus tibia. When seating of the tibial guide rod is incomplete or when the tibia has a valgus anatomic bow, cross-checking with extramedullary alignment devices is recommended to maximize accuracy of tibial component position. PMID- 7866804 TI - One-week low-dose triple therapy: new standards for Helicobacter pylori treatment. PMID- 7866805 TI - Seroprevalence of Helicobacter pylori in residents of a hospital for people with severe learning difficulties. AB - OBJECTIVE: To assess the seroprevalence of Helicobacter pylori among the residents of a hospital for people with severe learning difficulties. DESIGN: Retrospective analysis of stored sera from the hospital residents and control sera from the local, non-residential population. METHODS: H. pylori immunoglobulin G antibody was measured in 424 hospital residents using an enzyme linked immunosorbent assay, taking an antibody level of > 10 units/ml as evidence of H. pylori infection. The results were compared with 267 age- and sex-matched controls. RESULTS: Seropositivity rates were significantly higher in the hospital residents than in controls for all ages. This was most marked among those under 40 years of age (87 versus 24% H. pylori-positive for residents and controls, respectively; P < 0.001). The overall seropositivity rates were 87 and 43% for residents and controls, respectively (P < 0.001). CONCLUSIONS: This English study of H. pylori seroprevalence in an institutionalized population is the largest to date and confirms the very high seropositivity rates found by previous studies in Australia. Our findings may have significance for the future health of these patients and for the possible modes of transmission of H. pylori. PMID- 7866806 TI - Effect of sulglycotide in the prevention of duodenal ulcer relapse. AB - OBJECTIVE: To evaluate the effectiveness of sulglycotide, a gastroprotective drug, as maintenance treatment for patients with duodenal ulcer. DESIGN: A randomized double-blind study. METHODS: A total of 119 patients with recently healed duodenal ulcers were randomly allocated, in a double-blind fashion, to receive sulglycotide 200 mg twice daily (60 patients) or placebo (59 patients) for 1 year. Patients underwent clinical assessment every third month and endoscopy at 6 and 12 months, or earlier if relapse was suspected. RESULTS: The cumulative endoscopic relapse rates, compared using the log rank test, were 37 and 52% after 6 and 12 months, respectively, in the sulglycotide group and 62 and 71% (P = 0.03), respectively, in the placebo group. CONCLUSIONS: Sulglycotide is moderately effective as a maintenance treatment for duodenal ulcer disease. PMID- 7866807 TI - Glass and antimony electrodes for long-term pH monitoring: a dynamic in vitro comparison. AB - OBJECTIVE: To compare the performance of combined glass microelectrodes with monocrystalline and polycrystalline antimony electrodes with external reference in a 24-h dynamic in vitro study. DESIGN AND METHODS: In an artificial stomach, the pH of the contents titrated from pH1-7 and back by NaOH and HCI was simultaneously measured at 37 degrees C with antimony and glass probes connected to three recording devices. The recorded data were compared with data monitored continuously by a laboratory pH measurement system. The sensitivity and drift of glass microelectrodes were also analysed in intensive-care unit patients during intragastric pH monitoring for up to 96 h. RESULTS: The sensitivities of antimony polycrystalline, monocrystalline and of glass electrodes were 54.6, 55.3, and 61.8 mV/pH, respectively. The hysteresis was 6.4, 7.2 and 2.75 mV for antimony polycrystalline, monocrystalline and for glass electrodes, respectively. The drift in 24 h was -0.1 pH for glass over the pH range 1-7, and +0.3 pH over pH 1 2.5, and +0.15 pH over pH 2.5-7 for both of the antimony electrodes. The response times of both antimony and glass electrodes were similar over the pH range 2.5-7. The difference in the percentages of time below pH 1.5 was significant: 28.2% for glass, 17.3% for antimony polycrystalline and 18.1% for monocrystalline electrodes, respectively (P < 0.05). However, the difference in the percentages of time below pH 4 was not significant. After 96 h intragastric pH monitoring in six intensive-care unit patients, the mean drift of glass electrodes was 0.15 pH (range, pH 0.1-0.2) and the mean change in sensitivity 1.2%. CONCLUSIONS: (1) Antimony electrodes may be acceptable for intra-oesophageal pH monitoring but are not suitable for intragastric use. (2) The use of glass microelectrodes is recommended for intragastric pH monitoring, particularly when extended monitoring over periods longer than 24 h is required. PMID- 7866808 TI - Human oesophagus: a convenient antigenic substrate for the determination of anti endomysium antibodies in the serological diagnosis of coeliac disease. AB - OBJECTIVE: Immunoglobulin (Ig) A-class anti-endomysium antibodies are superior to other current antibody tests for detecting coeliac disease. We aimed to evaluate the suitability of human oesophagus for the determination of anti-endomysium antibodies. DESIGN: The specificity of monkey and human oesophageal tissue as antigenic substrate were compared using indirect immunofluorescence analysis. PATIENTS AND METHODS: Overall, 159 individuals were studied: 56 patients with biopsy-proven coeliac disease (39 with active disease) and 103 controls. The patients' IgA-class anti-endomysium antibodies were compared using unfixed cryostat sections of human and monkey oesophagus. Indirect immunofluorescence analysis was performed with an initial serum sample dilution of 1:5, and if positive, the highest dilution yielding a positive reaction was reported. RESULTS: The anti-endomysium antibody test was positive in 38 out of 39 patients with active coeliac disease using monkey oesophagus (sensitivity 97%) and in all 39 patients with active coeliac disease using human oesophagus (sensitivity 100%). Ten out of 17 coeliac patients on a gluten-free diet had positive anti endomysium antibodies using monkey oesophagus and 12 using human oesophagus as the antigenic substrate. This test was negative in all 103 controls using both substrates. CONCLUSIONS: Our study shows that human oesophageal tissue can be used instead of monkey tissue for determining anti-endomysium antibodies. Human tissue is a more sensitive antigenic substrate than monkey oesophagus and can be used to determine low titres of antibodies. Improving the diagnostic sensitivity of the anti-endomysium antibody test would make an important contribution to screening for coeliac disease. PMID- 7866809 TI - Endoscopic ultrasonography in the treatment of oesophageal varices by endoscopic sclerotherapy and band ligation: do we need it? AB - OBJECTIVE: To assess the role of endoscopic ultrasonography (EUS) in monitoring the treatment of oesophageal varices by endoscopic sclerotherapy and band ligation. METHODS: We studied 35 patients with portal hypertension undergoing elective treatment for oesophageal varices by injection sclerotherapy with absolute ethanol (group 1, n = 19) or by endoscopic variceal ligation (EVL; group 2, n = 16). All patients were examined by EUS before treatment to assess the status of their oesophago-gastric varices and the presence of collateral and perforating veins. Evaluation with EUS was repeated to confirm variceal eradication whenever endoscopy suggested successful obliteration, or to determine the reason for failure when treatment did not appear to be successful. Depending on the endosonographic findings, treatment was continued until EUS showed complete variceal eradication. RESULTS: After treatment, EUS showed insufficient variceal thrombosis in six (17%) patients who appeared to have variceal eradication at endoscopy. EUS was also superior to endoscopy for diagnosing gastric varices and showed patent vessels in 26 (74%) out of 35 patients. Gastric varices observed on EUS were detected at endoscopy in only 60% of cases. Endoscopic sclerotherapy and EVL had induced characteristic changes on EUS evaluation, and oesophageal fibrosis was observed more frequently in endoscopic sclerotherapy than in EVL-treated patients. CONCLUSION: EUS provides valuable information on the status of oesophago-gastric varices and can be used to assess the efficiency of endoscopic sclerotherapy and EVL. PMID- 7866810 TI - Dietary habits as risk factors for inflammatory bowel disease. AB - OBJECTIVE: To examine the influence of dietary factors in Italian patients with ulcerative colitis and Crohn's disease. DESIGN: We studied dietary habits immediately prior to the onset of disease in 104 patients enrolled in a prospective, epidemiological study of the incidence of inflammatory bowel disease in Italy. METHODS: Each patient was interviewed using a recall questionnaire to provide information on the daily intake of nutrients. The differences in diet between patients and healthy subjects matched for age, sex and city of residence were determined. RESULTS: Our data confirm that patients with Crohn's disease and ulcerative colitis have a high intake of total carbohydrate, starch and refined sugar. This resulted in a significantly higher relative risk (P < 0.001) in both ulcerative colitis and Crohn's disease patients. Total protein intake was significantly higher in ulcerative colitis, but not in Crohn's disease patients, than in controls. Fibre consumption did not differ between patients and controls. CONCLUSIONS: Our results confirm that carbohydrate consumption is significantly higher in IBD patients than in healthy controls. Ulcerative colitis patients also consumed more total protein than controls. The pathogenetic significance of these findings, however, remains unclear. PMID- 7866811 TI - Toxicity of laxatives: how to discriminate between myth and fact? PMID- 7866812 TI - Investigation of neutrophil migration into the gut by cytology of whole gut lavage fluid. AB - OBJECTIVE: Radiolabelling studies have shown that neutrophils migrate into the gut lumen in inflammatory intestinal diseases. We aimed to establish whether whole gut lavage fluid can be used to investigate intestinal neutrophilia. DESIGN: A prospective single centre study comparing inflammatory bowel disease patients, patients with other gastrointestinal diseases and normal controls. METHODS: Gut lavage with a polyethylene glycol-based solution was performed in 56 patients (29 with inflammatory bowel disease). Gut lavage fluid samples were collected when the rectal effluent was clear. Cells were then separated by density gradient centrifugation, counted, and cytospin preparations examined. RESULTS: High cell counts (> 3.7 x 10(5)/ml), predominantly neutrophils, were present in 12 out of 29 inflammatory bowel disease patients and in two out of 27 others. High cell counts and luminal neutrophilia characterized active ulcerative colitis and active colonic Crohn's disease, but not active small bowel Crohn's disease, or inactive disease. CONCLUSION: Whole gut lavage fluid samples can be used to investigate luminal inflammatory cells. We observed previously unrecognized differences between small bowel and colonic Crohn's disease using this method. The mechanisms of neutrophil migration into the gut lumen may differ with disease distribution. PMID- 7866813 TI - Air enema radiology compared with leukocyte scintigraphy for imaging inflammation in active ulcerative colitis. AB - OBJECTIVE: To compare air enema radiology with a leukocyte scintigraphy technique using technetium-99m-hexamethyl propylene amine oxime-labelled leukocytes for imaging colonic inflammation in ulcerative colitis. DESIGN: Prospective study in a University hospital. One radiologist and one nuclear physician independently graded the degree of inflammation in six colon segments per patient using radiographs and leukocyte scans. PATIENTS: Twenty consecutive patients with symptoms of active ulcerative colitis requiring corticosteroids, inflammation on rigid sigmoidoscopy and a positive leukocyte scan above the rectum. RESULTS: Using air enema radiology, inflammation above the rectum was observed in 17 of the 20 patients. Eleven patients had the same extent of disease with both imaging techniques (total n = 5; extensive n = 3; distal n = 3). Seven patients had more widespread colitis using leukocyte scintigraphy. In the remaining two patients with extensive inflammation at scintigraphy, air enema films showed total colitis. When the colon was subdivided into six different segments, prediction of the presence of inflammation in individual segments was 0.88 for air enema radiology compared with leukocyte scintigraphy and 0.60 for the prediction of absence of inflammation. All segments with an irregular mucosal contour or ulceration on air enema films had intense inflammation at scintigraphy. CONCLUSIONS: In patients with active ulcerative colitis, air enema radiology underestimates the extent of inflammation because this investigation shows secondary patho-anatomical changes, while leukocyte scintigraphy visualizes the acute cellular infiltrate. In patients with more severe inflammation, there is excellent agreement between the two methods. PMID- 7866814 TI - Unwanted anal penetration as a physical cause of faecal incontinence. AB - OBJECTIVE: To investigate sexual abuse as a cause of faecal incontinence. PATIENTS: Seven patients (two men and five women) with a history of sexual abuse, including anal penetration, and faecal incontinence. METHODS: Anorectal physiological techniques and anal endosonography were used for patient assessment. RESULTS: All seven patients had evidence of internal sphincter disruption and three had additional external anal sphincter dysfunction. CONCLUSION: Unwanted anal penetration can cause permanent structural anal sphincter damage. PMID- 7866815 TI - Cisapride in chronic idiopathic constipation: can the colon be re-educated? Bavarian Constipation Study Group. AB - OBJECTIVE: To investigate whether dose tapering and, potentially, withdrawal of cisapride is possible without loss of therapeutic effect. PATIENTS: A total of 119 patients with chronic constipation (less than three spontaneous, i.e., not laxative-induced, stools per week). DESIGN: Randomized double-blind study. METHODS: Group A (n = 56) was treated with cisapride 20 mg twice daily for 12 weeks. Treatment was continued for a further 12 weeks during which the patients were allowed to take a maximum of four tablets containing 5 mg cisapride each (maximum daily dose, 20 mg). Group B (n = 63) was treated with cisapride 20 mg twice daily for 6 weeks and then with cisapride 10 mg for 6 weeks. Treatment was then stopped and follow-up was continued for a further 12 weeks. RESULTS: Stool frequency was increased in both groups during active treatment and was not reduced when the dose was decreased from 20 mg to 10 mg twice daily in group B but was maintained in group A. Laxative intake fell by 50% in both groups, but this effect was maintained during follow-up in group A only. Group A patients took nearly the maximum dosage of cisapride tablets allowed during follow-up (3.3 tablets per day +/- 0.2 SEM). CONCLUSION: This study confirmed the efficacy of cisapride in chronic idiopathic constipation. Dose tapering below 15-20 mg per day, however, does not appear to be possible. PMID- 7866816 TI - Perineal descent at defecography in women with straining at stool: a lack of specificity or predictive value for future anal incontinence? AB - OBJECTIVE: To determine (1) whether patients complaining of straining at stool have pelvic floor descent and anal abnormalities similar to those of patients with anal incontinence and (2) whether these patients are prone to develop anal incontinence. METHODS: To answer the first question we used defecography to study perineal floor position at rest, during maximal contraction of the anal sphincter and during straining, and we performed anorectal manometry in 46 women with straining at stool but without anal incontinence at the beginning of the study, and in 46 women with idiopathic anal incontinence, matched for age. To answer the second question, we performed a 5-year follow-up study to determine whether anal incontinence had developed in those women with straining at stool. RESULTS: Perineal floor position at rest, during maximal contraction of the sphincter and during straining, resting pressure in the upper part of the anal canal, maximal amplitude and duration of the voluntary contraction were similar in the 46 women with straining at stool and the 46 women with idiopathic anal incontinence. In the follow-up study, 24 of the 46 women with straining at stool were contacted. The incidence of anal incontinence after 5 years was higher among these 24 women than in a control group of 20 women (13 out of 24 versus three out of 20, for women with straining at stool versus controls respectively; P < 0.01). The 13 patients with straining at stool who became incontinent had, at the initial investigation, a lower maximal amplitude of voluntary contraction, greater perineal descent at rest and less elevation of the pelvic floor during maximal contraction of the anal sphincter than the other women (P < 0.05). CONCLUSION: Women with chronic straining at stool have perineal descent at rest and during straining similar to that of incontinent women. Women with chronic straining are also prone to develop anal incontinence, suggesting that perineal descent at defecography in women with straining at stool may predict future anal incontinence. PMID- 7866817 TI - Prognostic value of p53 in Barrett's oesophagus. AB - During the last 30 years, the incidence of oesophageal adenocarcinoma has increased rapidly. Patients with Barrett's oesophagus have an increased risk of developing oesophageal adenocarcinoma and should be kept under surveillance. However, only a subset of Barrett's oesophagus patients will eventually develop malignancy and surveillance programs using endoscopy and histopathology cannot efficiently identify this subgroup. The study of additional prognostic factors is therefore of major importance and the p53 tumour suppressor gene has attracted much attention in this respect. Several investigators have found that p53 alteration is a frequent event in oesophageal adenocarcinomas and is associated with malignant transformation of Barrett's oesophagus. p53 appears to be a promising prognostic marker in Barrett's oesophagus and, as research progresses, possible clinical applications are emerging. PMID- 7866818 TI - Cholestatic jaundice induced by spontaneous disruption of an oestrogen implant. AB - OBJECTIVE: To describe the case of a women with cholestatic jaundice induced by the spontaneous fragmentation of an oestrogen implant. PATIENT: A 48-year-old woman, who presented with jaundice, pruritus and a flu-like illness 2 weeks after the insertion of a 100 mg oestradiol implant into her right buttock. INTERVENTIONS: At presentation the implant was removed and found to be fragmented. Investigations revealed an oestradiol level of 1548 pmol/l and an oestrogen-induced cholestatic jaundice. RESULTS: After removal of the implant and progesterone therapy, the patients symptoms resolved. CONCLUSION: This is the first reported case of cholestatic jaundice induced by a subcutaneous oestrogen implant. PMID- 7866819 TI - Spontaneous haemoperitoneum caused by ruptured varices in a patient with non cirrhotic portal hypertension. AB - OBJECTIVE: To report the case of a patient with a spontaneous, massive and fatal intraperitoneal haemorrhage from porto-systemic collaterals, caused by portal hypertension. We also review the cases of 18 cirrhotic patients with spontaneous bleeding of intraperitoneal varices and no previous abdominal surgery reported in the literature. PATIENT: A 21-year-old man with nodular regenerative hyperplasia, who had not undergone any previous surgery and who had large oesophageal varices diagnosed 3 years previously. CONCLUSION: To our knowledge, this is the first case of spontaneous intra-abdominal bleeding from collateral vessels in a non cirrhotic patient. PMID- 7866820 TI - One-week low-dose triple therapy for the eradication of Helicobacter pylori infection. AB - OBJECTIVE: To evaluate the efficacy and safety of two 1-week low-dose triple therapy regimens for the treatment of Helicobacter pylori infection. PATIENTS AND METHODS: Eighty patients with H. pylori infection and peptic ulcer disease (n = 64) or functional dyspepsia (n = 16), with similar demographic and clinical characteristics, were treated for 1 week with either omeprazole 20 mg once in the morning and clarithromycin 250 mg and metronidazole 400 mg twice daily (OCM; n = 40) or with omeprazole 20 mg once in the morning and clarithromycin 250 mg and tetracycline 500 mg twice daily (OCT; n = 40). H. pylori infection was assessed by urease test, culture and histology performed before and 4 (or more) weeks after cessation of the eradication therapy. RESULTS: H. pylori infection was treated successfully in 38 out of 40 patients by OCM and in 26 out of 40 patients by OCT (95 versus 65%, respectively; P = 0.0015). The OCM regimen was well tolerated in all patients except for one who complained of epigastric pain. Three patients on the OCT regimen reported side effects (abdominal pain, diarrhoea, pruritus), two of whom discontinued the study medication after 1 day. CONCLUSIONS: The 1-week low-dose triple therapy comprising omeprazole, clarithromycin and metronidazole was highly effective in eradicating H. pylori and was well tolerated. The replacement of metronidazole by tetracycline resulted in a significant decrease in the eradication rate. PMID- 7866821 TI - Bleeding into a liver cyst can be treated conservatively. AB - OBJECTIVE: To report the case of a patient with haemorrhage in a large hepatic cyst. PATIENT: A 66-year-old man, who presented with right shoulder pain and subsequent sudden abdominal pain. A large hepatic cyst containing blood was found at ultrasonography. INTERVENTIONS: The patient was treated conservatively. RESULTS: The patient's symptoms resolved quickly. No symptoms or complications recurred during a follow-up of 2 years. CONCLUSION: Therapy for non-parasitic liver cysts is indicated when symptoms or complications related to the cysts occur. This case shows that spontaneous haemorrhage into a non-parasitic hepatic cyst may follow a benign course and may be treated conservatively. PMID- 7866822 TI - The iatrogenic spine. PMID- 7866823 TI - A taxonomy of lumbar stenosis with emphasis on clinical applicability. AB - A taxonomy of stenosis is presented. The classifications of clinical symptoms and signs may help the clinician to understand the clinical problem and assist him in the decision-making process, particularly as related to the choice of diagnostic procedures. The classifications of radiological and pathoanatomical data may guide the surgeon in selecting the surgical approach and in deciding what amount of which tissue has to be removed at operation. PMID- 7866824 TI - The effect of vibration on back discomfort and serum levels of von Willebrand factor antigen: a preliminary communication. AB - The von Willebrand factor (vWf) is a complex protein whose release is a marker for endothelial damage; serum levels of its antigen (vWFAg) can be used as a marker for such changes. We measured the levels of back discomfort and vWFAg in 11 subjects following 25-min periods of (1) lying down, (2) sitting upright, (3) vibrating whilst sitting and (4) sitting upright. Back discomfort appeared and vWf levels were significantly increased following sitting upright, compared with lying flat, and increased further following vibration. They fell thereafter with a period of sitting still upright. These results demonstrate that vibration has a significant effect in increasing back discomfort and the serum levels of vWFAg, and it is possible that vibration may induce vascular damage within the spine. PMID- 7866826 TI - The "tear drop" (or avulsed) fracture of the anterior inferior angle of the axis. AB - Fourteen cases of an anterior inferior angle fracture of the axis treated in the Orthopaedic Department of the University of Athens from January 1970 to December 1992 were analysed. The mean follow-up time was 8.5 years. The so-called "tear drop" fracture of the axis composes a special entity characterised by an avulsed fragment, of varying size, from the anterior inferior angle of the body of the axis as a result of hyperextension. This type of injury is not a frequent one, representing 3% of the cervical spine trauma in our Department. There were eight men and six women with a mean age of 47 years. Road traffic accident is by far the most common mode of aetiology. The stability of this lesion is questioned by certain authors, resulting in disagreement concerning the choice of treatment to be followed. All the patients in our series were treated conservatively, consisting at the beginning with Glisson traction and then the use of a simple cervical collar. The rotation of the detached fragment, its anterior displacement, the posterior displacement of the vertebral body as well as the presence of instability at the C1-3 levels were analysed. The high incidence of co-existing lesions at the same or at a more distal level is discussed. This study revealed that there was no significant displacement of the vertebral body, and thus disturbance of the posterior ligaments, rendering the fracture stable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866825 TI - Fractures of the odontoid process: analysis of the functional results after surgery. AB - Eighteen patients who sustained type II/III fractures of the odontoid process, as classified by Anderson and D'Alonzo [2], underwent anterior screw fixation, as described in detail by Bohler [4] as well as Grob and Magerl [16]. Follow-up investigations 3, 12 and in some cases up to 60 months later confirmed sufficient functional results regarding the mobility of the upper cervical spine. The passive mobility of the cervical spine was analyzed by the radiographic evaluation technique of Dvorak and co-workers [12] and Penning [26], which revealed a hypomobility of the C2-3 segment 1 year after surgery in 11 patients and a fusion of the C2-3 vertebral bodies in 2 cases. The postoperative results including the rate of complications were compared with other authors's findings and different therapy concepts (e.g., posterior C1-2 arthrodesis, halo-vest treatment). PMID- 7866827 TI - Age- and sex-dependent force-related function of the cervical spine. AB - A total of 272 normal persons (109 men, 163 women) between the age of 14 and 84 years was studied for age, body weight, height, neck circumference and neck length. For evaluation of performance, a lifting test and an isometric extension force test showed sex- and age-specific differences in this group. A reliability test with two independent observers showed a good correlation of two consecutive measurements. The lifting test (PILE) and the isometric neck extension force test (IMPET) have been shown to be easy to administer, inexpensive and reliable. The data presented can be used as a data base for European persons for clinical research. PMID- 7866828 TI - The rate of recovery following whiplash injury. AB - Fifty consecutive patients with soft-tissue neck injuries following rear end collisions were studied prospectively to assess their rate of recovery. Patients were seen within 5 days of the accident, after 3 months, 1 year and 2 years, and their symptoms were classified into one of four groups (A, asymptomatic; B, nuisance; C, intrusive; D, disabling). Fourteen of 15 patients (93%) who were asymptomatic after 3 months remained symptom-free after 2 years. Of 35 patients with symptoms after 3 months, 30 (86%) remained symptomatic after 2 years. After 1 year, 26 (52%) stated that they had recovered completely, but after 2 years this had fallen to 19 (38%). Nine of the 15 patients who had improved between 3 months and 1 year deteriorated to their previous status, or worse, between 1 and 2 years. In asymptomatic cases, a prognosis that is 93% accurate after 2 years can be given after 3 months, and 86% of patients who are symptomatic after 3 months will remain so after 2 years. However, the severity of their symptoms will change during this period and will be at the same degree of severity in less than 50%. PMID- 7866829 TI - Prevention of the crankshaft phenomenon with anterior spinal epiphysiodesis in surgical treatment of severe scoliosis of the younger patient. AB - The aim of this study was to determine whether an anterior approach to the spine with a fusion of the growth centers of the anterior column of the spine, simultaneous by with a posterior fusion and instrumentation of the spine, in young patients with severe scoliosis who have considerable remaining growth, leads to prevention of the crankshaft phenomenon. Twelve patients who have had anterior fusion of the spine associated with posterior fusion and instrumentation of the spine were studied. In 10 of them, growth progression was demonstrated by modification of the Risser sign; for these patients no important progression of the spinal deformity was noted. One patient had no progression of the Risser sign and no progression of spinal deformity. One patient had progression of spinal deformity due to the disruption of the sacral anchorage of instrumentation. We think that this procedure leads to the prevention of the crankshaft phenomenon, and we recommend this procedure in young patients with severe scoliosis and considerable remaining growth. It must include all intervertebral levels of the rigid segment of the curve. PMID- 7866830 TI - Lumbosacral arthrodesis with louis technique. Review of 186 cases. AB - A retrospective study was carried out of 186 patients surgically treated by lumbosacral arthrodesis using Louis plates from 1981 to 1989 with an average follow-up of 7.2 years (range 3-11). The average age of the patients was 42.2 years (range 11-71). The indication for surgery was a herniated disc and segmentary instability in 29% (54 patients), spondylolysis or spondylolisthesis in 26.3% (49 patients), arthrosis in 11.3% (21 patients), instability (narrowing of the disc space and zygapophyseal hypertrophy) and stenosis in 5.9% (11 patients), tumour in 5.4% (10 patients), fractures in 0.5% (1 patient) and combinations of the above in 21.5% (40 patients who mainly had a herniated disc and associated spinal stenosis). Iliac crest autograft was used in 33 cases (17.7%), bank allograft in 5 (2.6%), and in the other 148 patients the graft was obtained from the arthrodesis bed. After follow-up we observed loosening of the screws in 20 patients and screw rupture in 10. We only documented 2 cases of pseudarthrosis using dynamic X-radiography. We conclude that the Louis plate is a simple method that leads to lumbosacral arthrodesis with a low rate of pseudoarthrosis. PMID- 7866831 TI - Anterior spondylodesis for spondylolisthesis: isthmic and degenerative types. AB - We studied the influence of instability of the spondylolisthetic segment upon anterior interbody fusion (AIF) rates. A one-level AIF of the lumbar spine by the modified extraperitoneal Bailey-Badgley fusion construct was performed in 26 patients with chronic or recurring acute low-back pain and/or other symptoms due to grades I and II spondylolisthesis. Sixteen were degenerative type, and 10 were isthmic type. Seventeen were female and 9, male. The average age was 41.2 years. The number of cases of spondylolisthesis at the level of L4-5 and L5-S1 as 18 and 8, respectively. In the 16 cases of degenerative type, 13 were grade I slip, and 3 were grade II slip, while in the 10 cases of isthmic type, 8 were grade I slip, and 2 were grade II slip. The average postoperative follow-up was 6 years (range 2-10 years). Solid fusion was obtained in 15 (93.8%) of the cases of degenerative spondylolisthesis and in 6 of the cases of isthmic type. Thus, the overall fusion rate was 80.7% (21 cases). However, some graft crumbling and redisplacement developed in 1 of the cases of degenerative type and 6 of the cases of isthmic type. Non-union developed in 4 (57.1%) of those 7 cases of graft crumbling (3 isthmic and 1 degenerative type). Fusion took 7 months on average (range 5-9 months). It is hypothesised that the isthmic-type spondylolisthesis had more instability than the degenerative one. Therefore, AIF in the case of degenerative spondylolisthesis is a useful procedure, while in the isthmic type it is not advisable as a routine procedure. PMID- 7866833 TI - Ossification of transverse atlantoid ligament in rheumatoid arthritis. PMID- 7866832 TI - Recurrent disc herniation in a man with ankylosing spondylitis. AB - Disc herniation in patients with Bechterew disease is rare; even rarer are recurrent disc herniations, a condition which we have not found described before. The patient was operated on with an excellent result. PMID- 7866834 TI - A comprehensive classification of thoracic and lumbar injuries. AB - In view of the current level of knowledge and the numerous treatment possibilities, none of the existing classification systems of thoracic and lumbar injuries is completely satisfactory. As a result of more than a decade of consideration of the subject matter and a review of 1445 consecutive thoracolumbar injuries, a comprehensive classification of thoracic and lumbar injuries is proposed. The classification is primarily based on pathomorphological criteria. Categories are established according to the main mechanism of injury, pathomorphological uniformity, and in consideration of prognostic aspects regarding healing potential. The classification reflects a progressive scale of morphological damage by which the degree of instability is determined. The severity of the injury in terms of instability is expressed by its ranking within the classification system. A simple grid, the 3-3-3 scheme of the AO fracture classification, was used in grouping the injuries. This grid consists of three types: A, B, and C. Every type has three groups, each of which contains three subgroups with specifications. The types have a fundamental injury pattern which is determined by the three most important mechanisms acting on the spine: compression, distraction, and axial torque. Type A (vertebral body compression) focuses on injury patterns of the vertebral body. Type B injuries (anterior and posterior element injuries with distraction) are characterized by transverse disruption either anteriorly or posteriorly. Type C lesions (anterior and posterior element injuries with rotation) describe injury patterns resulting from axial torque. The latter are most often superimposed on either type A or type B lesions. Morphological criteria are predominantly used for further subdivision of the injuries. Severity progresses from type A through type C as well as within the types, groups, and further subdivisions. The 1445 cases were analyzed with regard to the level of the main injury, the frequency of types and groups, and the incidence of neurological deficit. Most injuries occurred around the thoracolumbar junction. The upper and lower end of the thoracolumbar spine and the T10 level were most infrequently injured. Type A fractures were found in 66.1%, type B in 14.5%, and type C in 19.4% of the cases. Stable type A1 fractures accounted for 34.7% of the total. Some injury patterns are typical for certain sections of the thoracolumbar spine and others for age groups. The neurological deficit, ranging from complete paraplegia to a single root lesion, was evaluated in 1212 cases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7866835 TI - The anterior inferior angle fracture of a lower cervical vertebra. AB - Thirty-eight cases of a "tear drop" fracture of the lower cervical spine treated in our department during the last 20 years are reported. They represent 8.3% of all cervical injuries. We classified our cases into four types with regard to the extent of the bony lesion and the resulting posterior displacement of the vertebral body. Posterior displacement is of paramount importance. Neurological lesions were present in 52.6% of the patients, and they were related to the type of injury. Five patients died, and 33 were followed up for a mean period of 10 years. Five patients were operated on. All patients with a complete neurological lesion remained unchanged irrespective of the type of treatment. Incomplete neurological lesions showed a better tendency to recover after surgical treatment. Types III and IV are the more serious lesions, and they represent an absolute indication for surgical treatment. Type I is more benign and, if treated properly, has a good prognosis similar to type II. PMID- 7866836 TI - Spinal bone mineral density changes following halo vest immobilization for cervical trauma. AB - In this prospective study we followed the bone mineral density (BMD) changes of the injured cervical spine immobilized with the halo vest. In order to define the natural history of cancellous vertebral bone loss and restoration, dual-energy densitometry was used on each of ten selected cervical spines in the lateral view (1) immediately after the application of the device, (2) at the end of the treatment and (3) 3 months after the removal of the halo vest. The halo vest produces local osteoporosis in the immobilized cervical spine with an overall reduction of BMD averaging 2.83% (P < 0.05). The response of the cervical spine to immobilization was only slightly different from patient to patient and between different vertebral bodies in each particular spine. The type and the level of injury of the cervical spine were not related to the changes of BMD, age or gender of the patient, whereas the local osteoporosis was mostly reversible in the follow-up evaluation of 5-6 months. PMID- 7866837 TI - A prospective study of anterior cervical spondylodesis in intervertebral disc disorders. AB - In 1977, a prospective study of anterior cervical fusion was started in cases of intervertebral disc disorders with neuropathy and/or myelopathy up to 1986. A total of 193 patients was operated upon, of whom 179 were available for this study, with a mean follow-up time of 10.4 years (6-14 years) and a mean age of 51 years (28-76). There was an extensive record for every patient according to the protocol. The indication for operation was decided upon by an orthopaedic surgeon and a neurologist and was defined as discopathy with progressive neurological disorders, which did not respond to conservative therapy. The wearing of a stiff collar for 6 weeks during which time there was a improvement of the neurological symptoms was a strict precondition for the operation. Up to 5 levels were fused, with a mean of 2.3 levels per patient. During the operation a discography was performed on the symptomatic level(s) and the adjacent levels. All levels with positive discopathy were fused. In this long-term study the overall percentage of excellent and good results was about 82%. The results of fusions involving more than two levels were very encouraging. PMID- 7866838 TI - Prognostic criteria of discogenic paresis. AB - This discourse is aimed at elucidating prognostic criteria for the assessment of the course of a paresis in the case of lumbar disc herniation. Fourhundred and fifty patients were examined who had been operated on for lumbar disc herniation at the Orthopaedic University Clinic Mainz between 1986 and 1991. Of these, 240 showed radicular paralytic symptoms. They were examined prior to the operation, immediately afterwards and 1 year after the operation. The influence of the degree of intensity of the paresis, the time elapsed since the occurrence and other factors like nerve root affected, intraoperative findings, age, sex and weight of the patient were registered. It is obvious that the degree of intensity of a paresis is a good prognostic criterion for the assessment of the postoperative course. A paresis classified as grade III or IV receded in more than 70% of the cases within 6 months. For a paresis of grade II, the recovery rate was 40%. In the case of a total paresis, no complete neurological recovery was registered. The period of time which had elapsed since the occurrence of the paresis, the weight of the patient, the nerve root affected and other factors did not show any significant influence. As a criterion for an emergency or postponed operation on a herniated disc, the duration of paralytic symptoms should therefore be attributed less importance than the progression. PMID- 7866839 TI - Percutaneous nucleus pulposus denaturation in treatment of lumbar disc protrusions--a prospective study of 50 neurosurgical patients. AB - In a prospective study on 50 patients, the 1064-nm Nd-YAG laser was used to denaturate protruding lumbar discs. The method of Ascher [1] was modified using a saline pressure infusion system. Early results show a very good decompressive effect with 48 out of 50 patients in the categories very good and good. At follow up (mean 184 days postoperation) 31 out of 46 were in these categories, indicating a longer lasting retrieval of the protruded mass. A marked reduction of clinical nerve compression signs was noted. No severe complications occurred. Due to the irrigation system less low back pain was reported. The method seems promising in the standard neurosurgical setting. PMID- 7866840 TI - Long-term changes in the magnetic resonance image after chemonucleolysis. AB - After treatment of a symptomatic herniated disc with chymopapain, 14 patients were re-examined by magnetic resonance imaging (MRI) at a mean follow-up of 72 months. Well-defined MRI findings before chemonucleolysis were compared with those after the procedure by an independent observer. Five MRI parameters were assessed. No significant change was noted in the signal intensity of the affected disc, the extent of osteochondrosis and endplate reaction of the affected segment. The height of the affected disc as well as the size of the disc herniation were reduced significantly. The loss of the height is seen as a direct result of chymopapain activity, whereas the alteration of the size of the herniation seems to depend on the natural history of a disc herniation and is probably not a simple result of the treatment. PMID- 7866841 TI - Anterior lumbar fusion: results, assessment techniques and prognostic factors. AB - One hundred and fifty-one patients underwent anterior interbody lumbar spinal fusion for intractable back pain. A solid bony fusion was obtained in 76%. The method of outcome assessment profoundly affected the results; whereas 68% of patients rated themselves as significantly improved by the procedure, only 40% achieved a good or excellent result on the more objective low-back outcome score. Patients who underwent a second procedure did not do well, and "salvage" surgery is not recommended. Posterior distraction instrumentation neither increased the rate of union nor improved the final results. The rate of fusion was influenced by the presence of a compensation claim. Compensation status and psychological disturbance at presentation were significant prognostic factors. Psychological disturbance at review had a profound effect on the outcome and patient satisfaction ratings. It is recommended that future studies employ a recognised outcome score and that the analysis specifically includes compensation status and psychological disturbance. PMID- 7866842 TI - Osteoid osteoma of the axis. AB - A 15-year-old boy suffering from osteoid osteoma of the right lamina of the axis presented with torticollis and local pain without neurological deficits. The tumour was treated by en-bloc resection and laminoplasty with autogenous iliac crest. The follow-up at 14 months showed complete pain relief and a perfect incorporation of the transplanted bone. PMID- 7866843 TI - Bony vibration stimulation: a new, non-invasive method for examining intradiscal pain. AB - Fifty-seven patients with low-back pain were evaluated immediately prior to a discography examination by means of an electrical tool which produced bony vibration to the lumbar spinal processes. The vibrator was composed of a standard electric toothbrush shaft (Braun) with a blunt head instead of the brush. The lumbar spinal processes were compressed one by one for a few seconds with this blunt, vibrating tool. The patient's pain experience provoked by vibration was compared with that from injections during discography. A good correlation was found between these two examinations when patients with previously operated backs and painful, prolapsed discs were excluded: sensitivity was 0.96 and specificity 0.72. Prolapsed, but discographically painful discs were always painless in the vibration examination. The local, non-invasive bony vibration stimulation test is an easy, quick, safe, inexpensive and reliable method for examining intradiscal pain. PMID- 7866844 TI - Artifacts in magnetic resonance imaging of the spine after surgery with or without implant. AB - Magnetic resonance (MR) imaging is often disturbed after spine surgical procedures with or without an implant. Artifacts are induced by ferromagnetic or nonferromagnetic implants and devices and by small metallic particles left by surgical instruments. All metallic artifacts can affect the quality and usefulness of postoperative spine MR examinations. The physical effects caused by the introduction of metal or other conductive materials into a magnetic field and their consequences are presented. The application to postoperative spine MR examinations and solutions to reduce artifacts are discussed. PMID- 7866845 TI - A randomized study of manual therapy with steroid injections in low-back pain. Telephone interview follow-up of pain, disability, recovery and drug consumption. AB - A total of 101 outpatients with acute or sub-acute low-back pain was randomly allocated to one of two treatment groups. One group was given standardised conventional and optimised activating treatment by primary health care teams. The other group received, according to a pragmatic approach, another treatment programme including manipulation, specific mobilisation, muscle stretching, autotraction and cortisone injections. The treatment effect was evaluated by standardised telephone interviews 3, 7, 14, 21 and 90 days after the start of treatment. The two groups were similar in most of the pretrial variables, including age, sex, occupation, education, previous low-back pain problems, previous treatment, sick-leave, findings at the physical examination, quality-of life score, presence of common symptoms, disability rating and pain score. In the early phase as well as at the 90 days' follow-up, the group receiving manual therapy had significantly less pain, less disability, faster rate of recovery and lower drug consumption, indicating that this type of treatment is superior to conventional treatment. PMID- 7866846 TI - How reliable is lumbar nerve root sheath infiltration? AB - To determine the reliability of lumbar nerve root sheath infiltration, a prospective study was performed. Ninety-four patients were randomized into three groups. In the first group of 33 patients, 0.5 cc of dye (Telebrix N, 30 g) was applied at nerve root L4, in the second group of 30 patients, 1.0 cc, and in the third group of 31 patients, 2.0 cc. The infiltration was guided by computer tomography. The diffusion of the dye was documented with computed tomography of the affected segment L4-5. The images were evaluated by an unbiased observer. The results showed that in the first group the dye diffused to the adjacent ipsilateral nerve roots L3 and/or L5 in nine patients. In the second and third groups this diffusion was seen in 9 and 11 patients, respectively. A diffusion into the psoas muscle was documented in 4, 10 and 22 patients, respectively. These latter differences were statistically significant (P < 0.01). Diffusion into the psoas muscle is especially important because the nerve roots converge in this muscle to become a plexus, and they are no longer surrounded by their dural sheaths. Diagnostic lumbar nerve root sheath infiltration should be performed by an experienced examiner. To guarantee high reliability, the tip of the needle should be placed as near as possible to the affected nerve root. The amount of local anaesthetic should be as small as possible, 0.5 cc or preferably less. PMID- 7866847 TI - The posterior pelvic pain provocation test in pregnant women. AB - This study was done to evaluate a new, simple, non-invasive pain provocation test as an acid to differentiate between low-back and posterior pelvic pain in pregnant women. The test was performed on 72 pregnant women at various stages of pregnancy with or without low-back or posterior pelvic pain. The study was conducted by two physiotherapists with special interest in back pain in pregnancy at a normal antenatal clinic. The test was easy to learn, perform and interpret and was applicable throughout pregnancy. There was a strong correlation between a positive test answer and a history of posterior pelvic pain (P < 0.01, chi square). There were no side-effects. The test was highly specific and had a high positive prediction value for posterior pelvic pain and a high negative prediction value for low-back pain among pregnant women. PMID- 7866848 TI - Surgical treatment of lumbar spinal stenosis: patients' postoperative disability and working capacity. AB - A total of 439 patients operated on for lumbar spinal stenosis during the period 1974-1987 was re-examinated and evaluated for working and functional capacity approximately 4 years after the decompressive surgery. The assessment of subjective disability was based on the Oswestry low-back pain questionnaire. The proportion of excellent-to-good outcomes was 62% (women 57%, men 65%). The ability to work before or after the operation and a history of no prior back surgery were variables predictive of a good outcome. Before the operation 86 patients were working, 223 patients were on sick leave, and 130 patients were retired. After the operation 52 of the employed patients and 70 of the unemployed patients returned to work. None of the retired patients returned to work. In logistic regression analysis the ability to work preoperatively, age under 50 years at the time of operation and the absence of prior back surgery predicted a postoperative ability to work. Our results suggest that more attention should be focussed on the diagnosis of spinal stenosis and on the timing of the operative intervention. PMID- 7866849 TI - Morbus de Anquin or spinous engagement syndrome. A rare cause of low-back pain syndrome and sciatica. AB - We report on a rare disease called to Anquin's disease or spinous engagement or impingement syndrome. Low-back pain in this specific syndrome probably combined with sciatica is caused by a hypertrophic spinous process along with a spina bifida occulta of the underlying vertebra. Mostly, the enlarged spinous process is seen at L5 and the spina bifida occulta at S1. Conservative therapy consists of physiotherapy with postural exercises including improvement of lumbar flexion. If conservative treatment is unsuccessful, surgical treatment is indicated. Surgical therapy should include resection of the hypertrophic spinous process, probably combined with revision of the nerve roots and division of adhesions. Between 1981 and 1993 six patients were treated surgically after long-lasting periods of conservative therapy. All patients were re-examined clinically and radiologically after a mean follow-up period of 2.9 years. In all but one patient a distinct release from lumbar back pain and/or sciatica was observed. Regarding this, the most important fact in de Anquin's disease is to be aware of this specific syndrome. If low-back pain can be traced to a hypertrophic spinous process the first choice of therapy should be conservative. In unsuccessful cases simple surgical resection probably combined with division of the adhesion can lead to significant release from pain and is recommended. PMID- 7866850 TI - A comparative analysis of distraction rods versus Luque rods in thoracic spine fractures. AB - The findings of this study emphasize the importance of distraction in obtaining and maintaining reduction in upper thoracic fractures that are unstable and collapsing into kyphosis. It also shows that a Luque rectangle construct cannot fulfill this function adequately in this type of fracture. Thirty-four consecutive cases of surgically treated upper thoracic spine fractures were reviewed. Two patients died, and 4 were lost to follow-up, so after a minimum 6 month clinical and radiographic follow-up there were 11 patients in the Luque group and 17 in the distraction rod group. Preoperatively, there was no significant difference in age, sex, level of injury or severity of kyphosis between the two groups. The Luque stabilization took an average of 1 h longer. There was no difference in local, general or neurological complications between the groups. Pain at the final follow-up was the same according to analgesic use. The kyphosis in the Luque group increased progressively from preoperative to postoperative values continued and to increase. In the distraction rod group the postoperative kyphosis was improved compared with the preoperative values. At final follow-up the kyphosis had returned nearly to the preoperative values. The difference in the adequacy of the reduction as measured by percentage of anterior collapse between the two groups is highly statistically significant: distraction rod better postoperatively, P = 0.0114 (Student's t-test); distraction rod better at final follow-up, P = 0.0054 (Student's t-test). PMID- 7866851 TI - Neurological outcome after surgery for thoracolumbar fractures. A retrospective study of 93 consecutive cases, treated with dorsal instrumentation. AB - Surgical reconstruction and fusion form the treatment of choice for unstable thoracolumbar fractures. It remains difficult, however, to prove that surgical treatment provides an increased potential for neurological recovery. Also, the role of a decompressive laminectomy is still unclear. To address these issues, 93 consecutive cases of thoracolumbar fractures treated with dorsal instrumentation were reviewed. The neurological status at the time of admission and at a mean of 26 months postinjury was graded according to a modified Frankel scale. By using preoperative radiographs and computed tomography scans, we differentiated between fracture-dislocation lesions, dislocation lesions, flexion-distraction lesions, complete and incomplete burst fractures. Spinal stenosis was classified from grade 0 (no stenosis) to grade 3 (> 66% stenosis). All thoracolumbar fractures were treated with posterior instrumentation, using Dick's fixateur interne and Steffee's VSP plates and screws. During this procedure, laminectomy was performed in 33 patients (35%). In 17 cases (52% of the laminectomies), a surgically treatable lesion (dural tear, trapped nerve root, etc.) was found, especially in patients with a combination of a neurological deficit and a dislocation lesion, a fracture-dislocation lesion or a complete burst fracture with spinal stenosis grade 2 or 3. The neurological and functional outcome was excellent: none of the patients deteriorated, 68% made a complete neurological recovery, and 61% regained their previous level of activity. PMID- 7866852 TI - Odontoid fractures. Review of 150 cases and practical application for treatment. AB - A total of 150 odontoid fractures was treated over a 12-year period, 43 by anterior screw fixation. The rate of pseudarthrosis dropped from 20% to 5% in type II unstable fractures. Thus, anterior screw fixation seems to be safe and efficient, and may be more widely used to treat all type II and some type III fractures. Odontoid pseudarthrosis is usually tolerated quite well and therefore requires no correction. If necessary, anterior grafting with fixation can be proposed as an alternative for posterior fusion. PMID- 7866853 TI - Spontaneous burst fracture of the thoracolumbar spine in osteoporosis associated with neurological impairment: a report of seven cases and review of the literature. AB - This is a report of seven patients suffering from osteoporosis, who sustained unstable burst fractures in the thoracolumbar spine associated with neurological impairment, without trauma. The manner of presentation, the neurological involvement, the radiological findings, as well as the surgical treatment with respect to functional and neurological recovery are discussed. PMID- 7866854 TI - Klippel-Feil anomaly combined with fetal alcohol syndrome. AB - Alcohol is the most frequent and most important teratogenic noxa for the embryo and fetus. It may lead to deformation of all cells and organs. A case of Klippel Feil anomaly associated with fetal alcohol syndrome is described. The diagnosis of Klippel-Feil anomaly, even a late diagnosis made on the basis of rare deformities, is very important as the affected patients are at a high risk of alcoholism. The combination of Klippel-Feil anomaly with numerous other syndromes and deformities suggests a basic general disorder of skeletal maturation. Diverse cases of Klippel-Feil anomaly possibly originate, in reality, in an unrecognized fetal alcohol syndrome. PMID- 7866855 TI - Sciatic nerve palsy caused by haematoma from iliac bone graft donor site. AB - A 27-year-old woman developed a haematoma-related compressive neuropathy of the right sciatic nerve following the harvesting of a bone graft from the posterior aspect of the right iliac crest. The nerve was compressed in an enclosed compartment between the sciatic notch and the piriformis muscle, which is thought to be involved in the piriformis syndrome. The symptoms improved once the haematoma was evacuated, and this complication stresses the importance of adequate haemostasis of the area from which the bone graft is taken. PMID- 7866856 TI - The European Spine Society AcroMed Prize 1994. Acute thermal nerve root injury. AB - Bone cement is sometimes used for vertebral body reconstruction following tumor removal. During such procedures, the polymerization of the methyl-metacrylate in the bone cement generates heat. Such temperature increase might cause damage to the nerve roots within the spinal canal. In the present study, pig cauda equina nerve roots were subjected to controlled temperature increases by means of a heat generating probe. A temperature of 40 degrees C applied for 5 min did not cause any changes in nerve root function. However, 70 degrees C resulted in a complete block of nerve root function within 5 min. Histological nerve fiber damage was seen after exposure to 60 degrees C and 70 degrees C. The present study provides basic knowledge of heat-resistance properties of spinal nerve roots that might be directly applicable as guidelines for safety margins during surgical spine reconstruction procedures using bone cement. PMID- 7866857 TI - The importance of sonography in the diagnosis of septic complications following spinal surgery. AB - The detection of infection after surgery on the thoracic and lumbar spine is difficult due to the anatomical circumstances. Clinical symptoms, laboratory findings, and most radiological techniques are of limited diagnostic value. Among other benefits, sonography offers the advantage of early postoperative examination, even with metal implants in the operated area. In a retrospective study, 27 patients with clinically suspicious wounds were evaluated by sonography in the postoperative follow-up; all cases were verified by puncture and/or operative revision. Eleven cases turned out to be hematomas, and 16 cases were found to be infections. Accumulations of fluid, however, could not be differentiated by the established sonomorphological criteria such as internal echo structures, septation, demarcation from the environment, and reaction of the surrounding tissue. Ultrasonically guided transcutaneous needle aspiration biopsy served to differentiate the local findings and to establish the diagnosis and therefore is required as an obligatory method of investigation. PMID- 7866858 TI - Tomoscintigraphy of the lumbar spine: prospects and clinical application. AB - In an in vivo prospective study, we examined the lumbar spine of 18 patients presenting with a first episode of acute low-back pain with single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Scintigraphic activity at L2 was considered 100%, and the other levels were quantified in relation to L2. MRI scans were rated for disc signal intensity on T2-weighted images. The results show that an abnormal intervertebral MRI signal corresponds with an abnormal image on tomoscintigraphy. On tomoscintographic profiles, the disappearance of the 'discal dip' corresponds well with degeneration on MRI. Furthermore, a positive MRI at one level appears to influence other levels at which a significantly higher scintigraphic activity was observed. Of patients with acute LBP 50% had a normal disc SPECT; it is concluded that in these cases a non-discal origin for the pain must be sought. PMID- 7866859 TI - Spinal canal remodelling after stabilization of thoracolumbar burst fractures. AB - Spinal canal areas were measured prospectively in 22 consecutive burst fractures of the thoracolumbar junction, preoperatively, within 1 week postoperatively and 1 year after operation. Preoperative canal encroachment averaged 38% (range 10% 70%) of the estimated original area. The 11 patients with neurological impairment had a significantly more severe initial canal encroachment (mean 48%) than those who were neurologically intact (mean 33%). Postoperatively, canal encroachment had decreased to a mean of 18% (range 0%-62%). Within 12 to 15 months postoperatively, canal encroachment was further reduced by resorption of bone fragments to a mean of 2%. The largest observed remaining encroachment was 29%. The amount of bone resorption correlated significantly with the persistent postoperative encroachment. A critical appraisal of the methods used to assess the pre-fracture canal area revealed that reconstructing the vertebral foramen of the fractured vertebra on CT scans substantially overrated the original area as compared with averaging the canal area of the two adjacent vertebrae. PMID- 7866860 TI - Spinal canal restoration by posterior distraction or anterior decompression in thoracolumbar spinal fractures and its influence on neurological outcome. AB - Thirty consecutive patients who had suffered unstable fractures and dislocations of the thoracolumbar spine mostly associated with neurologic impairment and bony encroachment on the spinal canal were treated either with Harrington distraction rods combined with sublaminar wires or with the Zielke-VDS device. These patients were subsequently assessed for neurologic outcome, spinal canal clearance, sagittal and coronal spinal deformity correction preoperatively and postoperatively with a minimum follow-up of 26 months. In the follow-up evaluation, the patients who underwent surgery with Harrington rods showed an overall improvement of their neurologic function of 90.9%, whereas all patients who underwent the Zielke operation improved. Preoperatively, positive correlations were found between the level of injury and Frankel grades; the cord lesion tended to demonstrate more severe neurologic deficit when compared with cauda equina ones (P < 0.001). Furthermore, dislocation accompanying the injury resulted in a more severe neurological deficit (P < 0.05). Harrington rods and Zielke device offer sufficient initial correction of the frontal spinal deformity but did not significantly either restore or maintain sagittal plane alignment. The Harrington series showed an overall improvement of the segmental kyphosis of 26% (NS), with a subsequent loss of correction of 7.38% (NS) on the follow-up observation. The Zielke device produced an immediate, much better correction of the segmental posttraumatic kyphosis of 45% (NS), but a loss of correction of 22.9% (NS) was measured in the follow-up evaluation. Correction of the anterior and posterior vertebral height was shown to be better for the Zielke patient group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866861 TI - Effects of axial traction stress on solute transport and proteoglycan synthesis in the porcine intervertebral disc in vitro. AB - The effects of axial traction stress on intradiscal hydration, solute transport and proteoglycan synthesis were examined in 658 porcine coccygeal intervertebral discs in vitro. Measurements were performed in three tissue fractions: nucleus pulposus, inner and outer annulus fibrosus. At 0.80 MPa traction stress, the equilibrium hydration did not change in the nucleus pulposus. However, in the inner and outer annulus, the equilibrium hydration was reduced, and the change led to an increase of the effective fixed charge density. Diffusion of solute to the nucleus pulposus was significantly suppressed at 0.80 MPa traction stress. The fluid flow of the intervertebral disc tended to be suppressed during the creep recovery process after compression. The proteoglycan synthesis rate in the outer annulus was markedly suppressed by traction stress of 0.80 MPa for 4 h, but not that in the nucleus pulposus. These results suggest that a prolonged excessive axial traction stress induces a decrease in tissue hydration in the annulus fibrosus, and this may lead to an increase in the fractional volume of solid in the matrix and tissue osmotic pressure, resulting in diffusion inhibition of solute and suppression of proteoglycan synthesis. Thus, prolonged and excessive spinal traction may accelerate disc degeneration. PMID- 7866862 TI - Concomitant immunocytochemical study of macrophage cells and blood vessels in disc herniation tissue. AB - Twenty disc herniations (DH) were studied immunocytochemically for macrophages and blood vessels. Serial thin frozen sections were immunostained with an antibody specific for tissue macrophages (monoclonal antibody to CD68 antigen) and the endothelium of blood vessels (polyclonal antibody to von Willebrand factor). With this method, blood vessels, often abundant, were observed in as many as 16/20 (80%) of the DH studied, 12 disc extrusions and 8 sequestrated discs, whereas abundant macrophages were noted in 11/20 (55%) of the DH. Macrophages were present only in areas with blood vessels and had presumably infiltrated the tissue from them. As has been noted previously, some blood vessels are apparently newly formed as a result of tissue injury, whereas others were present in the disc prior to herniation. This is suggested by the lack of a clear correlation between the presence or absence of blood vessels and the preoperative duration of radicular pain. In areas of the DH where cartilage fragments occurred, both macrophages and blood vessels were particularly abundant. PMID- 7866863 TI - A further development in spinal instrumentation. Technical Commission for Spinal Surgery of the ASIF. AB - The purpose of this paper is to describe the concepts and use of a new, versatile instrumentation system, the universal spine system (USS), that has been designed to have wide application for pathology of the thoracolumbar spine. Many instrumentation systems for thoracolumbar spinal surgery now exist that were each originally designed to address specific areas of spinal pathology. For example, the recent systems designed to treat scoliosis deformities do not provide the instrumentation and implant support to adequately address other spinal disorders, such as fractures. In addition, most posterior implant systems were not designed for use anteriorly, and vice versa. As a result, surgeons have been required to become familiar with several different instrumentation systems in order to meet the varied needs of a spinal surgery practice. The objective of designing a new system was to simplify the surgical treatment of the commonly encountered spinal disorders by providing the surgeon with a single set of instruments and implants that could be used to treat tumors, trauma, deformities, and degenerative conditions affecting the thoracolumbar spine, via either an anterior or a posterior approach. This paper describes the development of the concepts, instruments, and implants of the USS and provides examples of its application in several case illustrations. PMID- 7866864 TI - Rapid and specific detection of pathogenic Leptospira species by amplification of ribosomal sequences. AB - We have developed an assay for the detection of pathogenic Leptospira that is based on the polymerase chain reaction. With the combination of agarose gel electrophoresis and blotting, pathogenic Leptospira can be discriminated specifically from nonpathogenic Leptospira and other bacterial species. This method, based on the amplification of 16S ribosomal RNA sequences, is able to detect 10 leptospiral cells/mL in cattle urine samples and 100 leptospiral cells/mL in pig urine samples. Using this assay leptospires were detected in urine samples from cattle that were experimentally infected with Leptospira interrogans serovar hardjo type hardjobovis. PMID- 7866865 TI - Inverse polymerase chain reaction. An efficient approach to cloning cDNA ends. AB - The conventional polymerase chain reaction (PCR) requires that DNA sequences at both ends of the region to be amplified be known. Inverse PCR (IPCR) and anchored PCR overcome this limitation and amplify flanking unknown DNA sequences by utilizing inverse amplification and a universal primer, respectively. The major advantage of IPCR is that two gene-specific primers are reserved for specific and efficient amplification of the unknown cDNA ends on the basis of a small stretch of known sequence. The protocol consists of five steps: reverse transcription, synthesis of second strand cDNA, circularization of double strand cDNA, reopen the circle DNA, and amplification of the inverse DNA fragment. PMID- 7866866 TI - Reporter enzymes for the study of promoter activity. AB - This article describes the use of three reporter enzymes used to study promoter activity in transgenic animals. Chloramphenicol acetyl transferase may be assayed by a nonchromatographic method that is rapid and sensitive. beta-Galactosidase is measured by a photometric assay and luciferase is assayed by measuring the emission of light using a luminometer. The relative merits of each enzyme is discussed. The use of reporter enzymes provides a rapid and sensitive method for analysis of transgene expression. PMID- 7866867 TI - Bacterial genome mapping by two-dimensional pulsed-field gel electrophoresis (2D PFGE). AB - Macrorestriction mapping is often the first step toward a thorough physical and genetic characterization of a bacterial genome. The problem of deducing the order of partially or completely digested macrorestriction fragments to yield a physical genome map may readily be solved by applying two-dimensional pulsed field gel electrophoresis (2D-PFGE) techniques. These powerful methods are quick and technically easy to perform; specifically, they are independent of DNA probes and should therefore be applicable to any bacterial species irrespective of its prior genetic characterization. In this article, detailed step-by-step protocols are given to set up, run, and evaluate 2D pulsed-field gels. Two basic methods are described: partial/complete 2D gels of one restriction enzyme and complete/complete 2D gels of two different restriction enzymes. Other topics include preparation of bacterial genomic DNA, screening for suitable rare-cutting restriction enzymes and determination of optimal running conditions. Accompanied by many notes, these protocols are meant to offer the novice a sound and rapid access to these important methods. PMID- 7866868 TI - Characterization of the glycosylation status of proteins. AB - Proteins are posttranslationally modified by a number of mechanisms, by far the most significant of which in terms of the molecular mass and functional diversity is glycosylation. The oligosaccharide chains added shortly after biosynthesis at the ribosome, and further modified while the protein is translocated through the intracellular membranes, have multiple affects on transport, localization, stability, plasma membrane expression activity, and antigenicity. Characterization of the glycosylation patterns at each site around the protein is essential for detailed understanding of structure/function relationships and the design of potential therapeutic agents. This can be achieved by a series of chromatographic and physicochemical procedures including HPLC, GC, MS, NMR, and computer graphics molecular modeling, which culminate in information on monosaccharide sequence and linkage, glycoprotein conformation, and oligosaccharide-to-protein interactions. PMID- 7866869 TI - Resonance assignment strategies for the analysis of NMR spectra of proteins. AB - Determination of the high resolution solution structure of a protein using nuclear magnetic resonance (NMR) spectroscopy requires that resonances observed in the NMR spectra be unequivocally assigned to individual nuclei of the protein. With the advent of modern, two-dimensional NMR techniques arose methodologies for assigning the 1H resonances based on 2D, homonuclear 1H NMR experiments. These include the sequential assignment strategy and the main chain directed strategy. These basic strategies have been extended to include newer 3D homonuclear experiments and 2D and 3D heteronuclear resolved and edited methods. Most recently a novel, conceptually new approach to the problem has been introduced that relies on heteronuclear, multidimensional so-called triple resonance experiments for both backbone and sidechain resonance assignments in proteins. This article reviews the evolution of strategies for the assignment of resonances of proteins. PMID- 7866870 TI - A simple method to make better probes from short DNA fragments. AB - A detailed method is presented for the creation of head-to-tail multimers of short blunt restriction fragments, ligated into a plasmid vector in a single-tube reaction. Random priming of the concatemer insert readily yields hybridization probes of high specificity, unattainable from the short monomer fragments. PMID- 7866871 TI - Techniques and high resolution DNA size markers for pulsed field gel electrophoresis. AB - High resolution DNA size markers are described for pulsed field gel electrophoresis (PFGE). These markers provide resolution of 10-20 kbp over a size range from 10 kbp to more than 400 kbp and are produced by partial restriction digestion of lambda phage DNA concatemers (lambda ladder). High resolution markers extending to over 400 kbp are made by partial restriction digestion of lambda ladder embedded in agarose. Detailed methods are described for marker production and for DNA separation by contour-clamped homogeneous electric field (CHEF) electrophoresis. These markers and methods are useful for a variety of high resolution DNA mapping by PFGE. PMID- 7866872 TI - Genetic transformation of plants by protoplast electroporation. AB - This article describes an optimized protocol for the electroporation of tobacco mesophyll protoplasts together with notes and data on the effects of various parameters and suggestions for work with protoplasts of other species. In this protocol, electroporation is achieved by means of electrical pulses from a high voltage, capacitive-discharge unit. Procedures are described for measurement of protoplast viability with Evan's blue, the detection of transient expression of CAT and GUS gene plasmid constructs, and for the recovery of stable transformants based on selection for kanamycin resistance. PMID- 7866873 TI - Lectin affinity chromatography. AB - A protocol is described for the preparation of lectin affinity chromatography columns using purified lectins and preactivated matrices. A general method is given for the purification of glycoproteins on immobilized Con A. Methods for immobilizing Con A on CDI agarose, Affi-Gel 15, and carbonyldiimidazole-activated agarose are described. PMID- 7866874 TI - Some alternative coupling chemistries for affinity chromatography. AB - Three different coupling chemistries that have been tried and tested for use in affinity chromatography are described. These methods are particularly recommended for use by workers who do not have access to, or do not wish to use, complex organic chemical synthetic procedures. They have been demonstrated repeatedly to be reliable, efficient, low cost, and easily scaleable up or down in size. The periodate oxidation method works best with Sephacryl type gels and uses only low toxicity reagents and couples well to proteins with both high efficiency and high capacity. The vinyl sulfone method is more reactive and couples both carbohydrates and proteins. The bis-epoxide method, although less reactive, can be used under more extreme conditions of pH to couple otherwise unreactive molecules, such as synthetic polymers, drugs, and so forth. PMID- 7866876 TI - Characterization of antagonist and pathogenic Fusarium oxysporum isolates by random amplification of polymorphic DNA. PMID- 7866875 TI - Herpes simplex virus vectors for gene therapy. AB - Herpes simplex virus (HSV) has a number of advantages as a vector for delivering specific genes to the nervous system. These include its large size, wide host range, and its ability to establish long-lived asymptomatic infections in neuronal cells in which a specific region of the viral genome continues to be expressed. Unfortunately, the large size of this virus and difficulty in manipulating it has led to its use as a vector lagging behind that of other, smaller viruses such as the retroviruses. In addition, the virus's ability to replicate lytically in the brain, under some circumstances, causing encephalitis, has led to fears about its potential safety for ultimate use in humans. This review will discuss a number of new approaches that are aimed at rendering simpler the insertion of foreign genes into the virus and making it as safe as possible. Ultimately, these advances offer real hope for the use of HSV vectors in gene therapy procedures. PMID- 7866878 TI - Advances in diagnosing tomato yellow leaf curl geminivirus infection. AB - As a result of the spread of TYLCV on tomato crops, reliable and rapid diagnostic tools to identify and isolate new sources of infection are necessary. We tested several methods, based both on antibodies and on nonradioactive DNA probes. Indirect plate-trapping ELISA was only effective in detecting the virus in purified preparations, but not in crude extracts. Dot-ELISA with chemiluminescence detection gave satisfactory results when young stems were directly squashed on membranes. A digoxigenin-labeled probe, detected with chemiluminescence, was used in leaf squashes and dot blots. Best results were obtained with dot blots of total nucleic acids prepared with a fast and safe procedure. TYLCV DNA was readily and reliably detected in spots corresponding to 15 micrograms fresh weight. When weak signals were observed, total extracts were analyzed by Southern blotting, to confirm the presence of viral DNA forms. PMID- 7866877 TI - Potential of genes and gene products from Trichoderma sp. and Gliocladium sp. for the development of biological pesticides. AB - Fungal cell wall degrading enzymes produced by the biocontrol fungi Trichoderma harzianum and Gliocladium virens are strong inhibitors of spore germination and hyphal elongation of a number of phytopathogenic fungi. The purified enzymes include chitinolytic enzymes with different modes of action or different substrate specificity and glucanolytic enzymes with exo-activity. A variety of synergistic interactions were found when different enzymes were combined or associated with biotic or abiotic antifungal agents. The levels of inhibition obtained by using enzyme combinations were, in some cases, comparable with commercial fungicides. Moreover, the antifungal interaction between enzymes and common fungicides allowed the reduction of the chemical doses up to 200-fold. Chitinolytic and glucanolytic enzymes from T. harzianum were able to improve substantially the antifungal ability of a biocontrol strain of Enterobacter cloacae. DNA fragments containing genes encoding for different chitinolytic enzymes were isolated from a cDNA library of T. harzianum and cloned for mechanistic studies and biocontrol purposes. Our results provide additional information on the role of lytic enzymes in processes of biocontrol and strongly suggest the use of lytic enzymes and their genes for biological control of plant diseases. PMID- 7866879 TI - Analysis of gene expression by northern blot. AB - In the analysis of gene expression, the steady-state level of RNA transcripts is one of the most convenient parameters used to monitor the activity of an endogenous or introduced gene in cell lines and tissues. A variety of methods, such as S1 hybridization, RNase protection and Northern blotting, can be used to measure RNA levels. Which assay system is best depends largely on the type of information required, levels of sensitivity, and limitations of the particular in vivo system being examined. This article details the method for analyzing RNA by Northern blotting, which basically involves the isolation of RNA, its size fractionation by electrophoresis, transfer to a membrane, and detection by nucleic acid hybridization and autoradiography. PMID- 7866881 TI - Two-dimensional polyacrylamide gel electrophoresis of membrane proteins. AB - Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) is one of the most powerful separation techniques for complex protein solutions. The proteins are first separated according to their isoelectric point, driven by an electric field across a pH gradient. The pH gradient necessary for the separation according to isoelectric point (pL) is usually established by electrophoresing carrier ampholytes prior to and/or concomitantly with the sample. The second dimension is usually a separation according to molecular size. Mostly this separation is performed after complete denaturation of the proteins by sodium dodecyl sulfate and 2-mercaptoethanol (SDS-PAGE). This standard method has considerable disadvantages when relatively hydrophobic membrane proteins are to be separated: cathodic drift, resulting in nonreproducible separation, and the denaturation of the proteins, mostly making it impossible to detect native properties of the proteins after separation (e.g., enzymatic activity, antigenicity, intact multimers, and so on). The protocols presented here take care of most of these obstacles. However, there is probably no universal procedure that can guarantee success at first try for any mixture of membrane proteins; some experimentation will be necessary for optimization. Two procedures are each presented: a denaturing (with urea) and a nondenaturing method for IEF in immobilized pH gradient gels using Immobilines, and a denaturing (with SDS and 2 mercaptoethanol) and a nondenaturing technique (with CHAPS) for the second dimension. Essential tips and tricks are presented to keep frustrations of the newcomer at a low level. PMID- 7866880 TI - Analysis of protein glycosylation by mass spectrometry. AB - There is a growing pharmaceutical market for protein-based drugs for use in therapy and diagnosis. The rapid developments in molecular and cell biology have resulted in production of expression systems for manufacturing of recombinant proteins and monoclonal antibodies. These proteins are glycosylated when expressed in cell systems with glycosylation ability. For glycoproteins intended for therapeutic administration it is important to have knowledge about the structure of the carbohydrate side chains to avoid cell systems that produce structures, which in humans can cause undesired reactions, e.g., immunological and unfavorable serum clearance rate. Structural analysis of glycoprotein oligosaccharides requires sophisticated instruments like mass spectrometers and nuclear magnetic resonance spectrometers. However, before the structural analysis can be conducted, the carbohydrate chains have to be released from the protein and purified to homogeneity, and this is often the most time-consuming step. Mass spectrometry has played and still plays an important role in analysis of protein glycosylation. The superior sensitivity compared to other spectroscopic methods is its main asset. Structural analysis of carbohydrates faces several problems, however, due to the chemical nature of the constituent monosaccharide residues. For oligosaccharides or glycoconjugates, the structural information from mass spectrometry is essentially limited to monosaccharide sequence, molecular weight, an only in exceptional cases glycosidic linkage positions can be obtained. In order to completely establish an oligosaccharide structure, several other structural parameters have to be determined, e.g., linkage positions, anomeric configuration and identification of the monosaccharide building blocks. One way to address some of these problems is to work on chemical pretreatment of the glycoconjugate, to specifically modify the carbohydrate chain. In order to introduce specific modifications, we have used periodate oxidation and trifluoroacetolysis with the objective of determining glycosidic linkage positions by mass spectrometry. PMID- 7866882 TI - Enhancing PCR amplification and sequencing using DNA-binding proteins. AB - The polymerase chain reaction (PCR) is a powerful core molecular biology technique, which when coupled to chain termination sequencing allows gene and DNA sequence information to be derived rapidly. A number of modifications to the basic PCR format have been developed in an attempt to increase amplification efficiency and the specificity of the reaction. We have applied the use of DNA binding protein, gene 32 protein from bacteriophage T4 (T4gp32) to increase amplification efficiency with a number of diverse templates. In addition, we have found that using single-stranded DNA-binding protein (SSB) or recA protein in DNA sequencing reactions dramatically increases the resolution of sequencing runs. The use of DNA-binding proteins in amplification and sequencing may prove to be generally applicable in improving the yield and quality of a number of templates from various sources. PMID- 7866883 TI - Joining together to provide quality trauma care. PMID- 7866884 TI - Geriatric trauma patients: initial assessment and management of shock. AB - Elderly trauma patients sustain distinct patterns of injuries, have a unique response to stress, and are more likely to suffer serious consequences to trauma compared to younger patients. The key to successful management of the older trauma patient is to maintain a high index of suspicion for serious consequences to relatively minor injuries and to use vigilant clinical observation. The author discusses the vital role nurses play in assessing and monitoring the elderly person's response to injury and treatment, reviews some of the physiologic changes associated with aging, and provides recommendations for management priorities during the initial shock phase. PMID- 7866885 TI - Nurses' knowledge and attitudes toward organ and tissue donation in a community hospital. AB - The author conducted a survey of 210 nursing staff members in a community hospital to identify their attitudes and knowledge about organ and tissue donation. Results showed that 32% (n = 68) of respondents identified the significant difference between organ and tissue donors and 53% (n = 112) described feeling uncomfortable discussing donation with families. Fifty-seven percent (n = 120) of those who had been involved with donor families in the past were more likely to feel comfortable discussing donation with family members. Other means for increasing awareness and referral are discussed also. PMID- 7866886 TI - The top 10 questions when a hospital is deciding to become a trauma center. PMID- 7866887 TI - Denervation of the transplanted heart: nursing implications for patient care. AB - The denervated heart requires significant changes in planning and implementing care. The loss of direct neural compensation in response to the body's demands is replaced by the denervated heart's reliance on preload augmentation to maintain cardiac output, stimulation of cardiac adrenergic receptor sites to promote inotropic and chronotropic responses, and the nurse's knowledge of transplant physiology to choose and administer directacting cardiovascular pharmacologic agents to treat common posttransplant complications and to safely and effectively manage the patient's care. PMID- 7866888 TI - Pancreas transplantation. AB - This article summarizes the historic and current perspectives related to pancreatic and islet cell transplantation. The nursing care of patients who are recipients of these types of transplantations is described. The complications and risks for these types of transplantations along with the most common surgical and medical regimens are also described. PMID- 7866889 TI - Pharmacologic immunosuppression: cure or curse? AB - With the advent of cyclosporine in the 1980s, transplantation has become the treatment of choice for many endstage organ diseases. However, there is a price to pay. Pharmacologic immunosuppression has numerous side effects, some of them serious. This article discusses traditional (corticosteroids and azathioprine), current (cyclosporine and antilymphocyte preparations), and future (FK 506, rapamycin, mycophenolate mofetil [RS-61443], brequinar, deoxyspergualin, and new monoclonal antibodies) immunosuppressive agents. How these drugs are used and their side effects are examined. Has a cure been provided? No; patients must continue medical care regularly and take medications daily. Is this a curse? If so, it is one most recipients would choose again. Perhaps both a cure and curse have been provided. Transplantation will become less of a curse and more of a cure as improvements in immunosuppression occur. PMID- 7866890 TI - Living related liver transplants: an option for pediatric patients. AB - Living related liver donation and transplantation is becoming a widely accepted option for the treatment of some pediatric end-stage liver diseases. A multidisciplinary approach is required to provide complex medical and nursing care to the transplant patient. As morbidity and mortality of living related liver recipients continue to compare favorably to those of cadaveric liver recipients, and as the organ donor shortage continues, an increase in the number of these procedures being performed can be expected. PMID- 7866891 TI - The role of the transplant advanced practice nurse. AB - Expert clinical experience and abilities, often combined with knowledge from other disciplines, provide a foundation from which the transplant advanced practice nurse can play a variety of roles. Whether performing direct patient care or influencing patients in such settings as the hospital, joint practice, home health care or community nursing, managed care organizations, a corporate environment, or as a nurse entrepreneur, transplant advanced practice nurses have an impact on care. This advanced practice role is challenging, rewarding, and vital. PMID- 7866892 TI - Assisting professionals in approaching families for donation. AB - This article identifies potential barriers that nurses and other health care professionals face when approaching families to offer the option of organ and tissue donation. Issues that are examined include personal feelings regarding dying, death, and organ donation; unclear roles for nurses and other health care personnel; nonsupportive institutions or physicians; difficulty in explaining brain death to families; fear of intruding during grief; lack of knowledge; and the need for support. Strategies are suggested to help nurses and other professionals to overcome these obstacles. PMID- 7866893 TI - Psychologic and psychosocial aspects of renal transplantation. AB - This article focuses on some of the more common psychologic and psychosocial issues which confront renal transplant patients and their families. Even though renal graft failure is not life threatening as it is in heart and liver graft failure, the renal transplant patient nonetheless undergoes psychologic turmoil and stress similar to that experienced by heart and liver transplant patients. Characteristic responses to these issues are presented along with suggested forms of intervention. PMID- 7866894 TI - Psychosocial considerations for bone marrow transplant recipients. AB - Psychosocial considerations for bone marrow transplant recipients include not only the patient's reactions to the illness and form of treatment, but also the effect and reactions the patient receives from family, friends and caregivers. This article highlights the particular psychosocial concerns of bone marrow transplant recipients before, during, and after bone marrow transplantation; their perceived quality of life after transplantation; and the impact of family, friends, and caregivers on their hospitalization and recovery phases of transplantation. PMID- 7866895 TI - Extracorporeal liver assist device: hope for the future. AB - The liver has the unique property of regeneration in an acute setting if given enough time. Currently the only successful intervention for liver failure, both acute and chronic, is orthotopic liver transplantation. The increasing cost of transplantation and subsequent medical care, coupled with the decreasing availability of transplantable organs, magnifies the need for an alternative solution. A liver assist device that is metabolically similar to a native liver will advance the treatment regimen and decrease the need for surgery. PMID- 7866896 TI - Nutritional management of the metabolically stressed patient. AB - The nutritional management of the critically ill metabolically stressed patient has changed drastically within the last two decades. Alterations in carbohydrate, fat, and protein metabolism following severe injury affect effective substrate utilization and the provision of nutritional or metabolic support. This article describes the acute alterations in carbohydrate, fat, and protein metabolism during severe metabolic stress; reviews nutritional assessment and requirements during metabolic stress; and presents recent findings that influence nutritional support during metabolic stress. The role of gut in the provision of nutritional support and the pharmacologic properties of select enteral nutrients are reviewed. PMID- 7866897 TI - [Mechanism of p53 gene mutation in the development of urologic cancer]. AB - With DNA polymerase chain reaction-single strand conformation polymorphism assay followed by direct DNA sequencing, p53 gene mutation was examined in bladder transitional epithelial cell carcinoma, renal cell carcinoma and testicular seminoma. p53 gene mutation was found in 7 cases (35%) of bladder carcinoma and 4 cases (23.5%) of testicular seminoma. Inactivation of Rb gene and activation of ras and c-erbB-2 were also studied. The results suggest that development of urologic neoplasms is closely associated with p53 gene mutation and involves loss of expression of Rb and aberrant expression of ras and c-erbB-2. PMID- 7866898 TI - [Application of polymerase chain reaction in the diagnosis of gonococcal urethritis]. AB - 84 suspected patients with gonococcal urethritis were diagnosed by polymerase chain reaction (PCR). It was demonstrated that 28 patients (33.3%) were positive, and 56 (66.7%) negative. Of the PCR-positive patients, 18 showed secretions from the urethral tract, on which the bacterial stain and culture were carried out. The results indicate that 12 patients were positive, and 6 negative. There was no patient with positive stain and culture with PCR-negative. We conclude that PCR is more specific and sensitive than other routine methods in the diagnosis of gonococcal urethritis, especially of chronic infection. PMID- 7866899 TI - [Detection on BCR-ABL fusion gene in Ph1 chromosome positive leukemia by "nested" retrotranscriptase/polymerase chain reaction]. AB - By using "nested" retrotranscriptase/polymerase chain reaction (RT/PCR) technique, we determined the expression patterns of the BCR-ABL fusion gene resulting from the chromosomal translocation t (9; 22) in leukemias with Ph1 chromosome. Three distinct isoforms of fusion gene transcripts were discovered: ela2, b2a2 and b3a2. In 10 cases of chronic myelogenous leukemia (CML), only two types (b2a2 and b3a2) were observed. However, in 8 cases of Ph1 chromosome positive acute lymphoblastic leukemia (Ph1 + ALL), all three types were detected, including two cases characterized by the coexistence of ela2 and b2a2 or b3a2 types. Moreover, the RT/PCR procedure established in the present study proved to be a very sensitive method, allowing the detection of one leukemic cell among 10(5)-10(6) normal cells. Thus, a positive RT/PCR result was obtained in two Ph1 + ALL cases just after chemotherapy-induced clinical remission (CR), suggesting the presence of residual disease. One case remained RT/PCR positive four months after achieving CR and relapsed in the fifth month, while the other case converted to RT/PCR negative eight months later and is now in CR for 18 months. Therefore the detection of BCR-ABL fusion gene is of importance not only in the study of the pathogenesis of Ph1 + leukemias but also in their diagnosis and monitoring of minimal residual disease during CR. PMID- 7866900 TI - [Low-dose recombinant human tumor necrosis-alpha in HL-60 leukemic cell line: effect on induced differentiation and regulating expression of c-myc, c-fos proto oncogenes]. AB - The promyelocytic leukemic cell line HL-60 with 20-200U/ml of low-dose rhTNF-a cultured in liquid culture system in vitro was used to observe the effect on HL 60 by TNF. TNF within dose of 50-200 U/ml can induce HL-60 cell differentiation along the monocytic-macrophage pathway, and inhibit HL-60 cell proliferation. The total RNA of HL-60 cell was used to hybrize to v-myc or v-fos probe by dot blot. We detected the expression changes of c-myc or c-fos proto-oncogene by 1-100U/ml of TNF inducing HL-60 cell for 1-12 hours. TNF could regulate the level of c-myc or c-fos mRNA, the transcription of c-myc was inhibited remarkdly, and the expression of c-fos was increased early. The results indicated that TNF in low dose have effect on inducing HL-60 cell differentiation and regulating expression of multioncogene. PMID- 7866901 TI - [Cloning and sequencing of nm23-H3b, a new gene identified to nm23]. AB - Nm23 is a kind of an effective tumor metastasis suppressor gene which included two types in human: nm23-H1 and nm23-H2. Amino acid identity between nm23-H1 and nm23-H2 was 88%. In this study, we used a pair of primers to flank the part of coding sequence of nm23. The 5'-translated sequence was amplified by PCR from human normal liver genomic DNA. A 375bp clone was characterized to designate pnm 23-H3b. The nm23-H3b nucleotide sequence between 40bp and 70bp was different from nm23-H1 and nm23-H2, and other sequences had 86% and 90% identical to nm23-H1 and nm23-H2, respectively. Southern blot containing Bg1II-digested human liver genomic DNA hybridized to the entire nm23-H3b DNA and showed three bands at 10.5, 7.9 and 4.0 kb. These data demonstrate that nm23-H3b is a new type of gene, which has high homology with human nm23-H1 and nm23-H2. Nm23 is possibly considered a family of closely related genes. PMID- 7866902 TI - [Hepatitis C virus RNA in tumor tissues of Chinese liver cancer patients]. AB - A total of 38 specimens of liver cancer and pericancerous tissues from 30 hepatocellular carcinoma patients were studied for hepatitis C virus (HCV) RNA by RT-PCR using primers from the s'non-coding regions of HCV viral genome. Serum anti-HCV of these patients was also assayed as a marker of infection. The results showed that 10/30 (33.3%) hepatocellular carcinoma (HCC) patients were infected by HCV, while 23/30 (76.7%) by hepatitis B virus (HBV). The HCV RNA from liver cancer tissues were characterized by type II and III through restriction enzyme digestion. Sequencing of the 5'-NC regions amplified revealed that this region was conserved. Since 8 of the 10 HCV infected HCC patients were coinfected with HBV, chronic infection caused by HCV and HBV might be one of the factors leading to HCC. PMID- 7866903 TI - [Targeting treatment of human HCC xenografts implanted in nude mice using bifunctional antibody HC-1 combined with mitomycin C]. AB - Bifunctional antibody (BFA) HC-1 possessing one binding site for mitomycin C (MMC) and a companion site directed against human hepatocellular carcinoma (HCC) cell membrane was constructed by chemical conjugation of two Fab' fragments of McAb MMC-1 and McAb HCMP-1. BFA could be specifically attached to tumor xenograft of nude mice bearing human HCC and thus simultaneously capture mitomycin C. The attachment of these complexes was detected by radioimmunoimaging in nude mice bearing human HCC using 131-I labelled BFA HC-1. Clear imaging of the tumor was obtained in 6 days after i.p. injection. On the 8th day after the injection, tumor/liver (T/L) ratio was 8.04 +/- 0.45. When the BFA HC-1 was used to be combined with MMC for the targeting treatment of human HCC implanted in nude mice, the highly significant suppression of tumor growth was achieved. After two months of treatment, xenografts of 40% (4/10) mice disappeared and 60% (6/10) of the mice survived. Those mice treated only with MMC became more and more sick even if the grafted tumors shrank, and all of them died within 2 months after therapy. The controls were treated with nonspecific IgG. Tumors grew very fast, and most of the controls died in 1 month after the first injection. The results suggest that BFA HC-1 could concentrate MMC on the human HCC cells, and it is a kind of suitable carrier for the targeting treatment of human HCC. PMID- 7866904 TI - [The effect of calmodulin antagonist on the anticancer effect of vinblastine]. AB - Calmodulin exists in all eukaryotic cells. It functions as the intracellular receptor of Ca, regulates various cellular physiological processes. We studied the effect of calmodulin antagonist W-7 on the anti-cancer effects of vinblastine. With the method that calmodulin can activate cyclic nucleotide PDE, we found that W-7 can significantly reduce the calmodulin level of MGC803 cell (P < 0.05). W-7 could not only increase the uptaking and accumulating of -3H Vinblastine in MGC803 cells (P < 0.05), but also decrease the IC50 of Vinblastine (from 12.0 +/- 0.03 nmol to 5.27 +/- 0.02 nmol) in MGC803 cells. It is indicated that calmodulin antagonist W-7 can enhance the anticancer effect of vinblastine. PMID- 7866905 TI - [The relation between prognosis and amplification of the c-erB-2 (HER-2/neu) proto-oncogene in ovarian carcinomas]. AB - C-erbB-2 (HER-2/neu) proto-oncogene is mainly expressed in epithelial tissue and activated due to its amplification. Amplification of the C-erbB-2 proto-oncogene is associated with poor prognosis in human ovarian cancer. We examined whether amplification of C-erbB-2 is common in ovarian carcinoma or is associated with poor prognosis. The DNA of ovarian carcinoma was extracted and consequently digested with restriction endonuclease EcoRI, electrophoresed in 0.8% agarose gels and blotted onto nitrocellulose filter with Southern transfering method. It was hybridized with a 32p-labelled C-erbB-2 probe and subsequently underwent autoradiography. It was shown that the C-erbB-2 (HER-2/neu) gene was amplified in 8 of 26 human ovarian carcinomas (30.8%). Clinically the 8 patients with the amplified C-erbB-2 were in their advanced stage (III-IV). Five of the patients died from 2 to 4 months after operation. These findings suggest that amplification of the C-erbB-2 gene may play a role in the pathogenesis of ovarian carcinoma, it is frequently observed in advanced ovarian carcinoma and associated with poor prognosis for these patients. PMID- 7866906 TI - [Assessment of coronary flow reserve in patients with angina pectoris]. AB - Coronary flow reserve was assessed by using a computer-assisted method in 26 normal controls and 45 patients with significant coronary artery stenosis ( > or = 50% luminal narrowing) and 16 patients with syndrome X. After intracoronary administration of papaverine, the diameter, cross sectional area, blood velocity, flow volume and reserve capacity of both left anterior descending (LAD) and right coronary arteries (RCA) were lower in patients with significant coronary stenosis than in controls. Despite similar changes in the diameter and cross sectional area, the velocity, flow volume and reserve capacity of these two vessels were also lower in patients with syndrome X than in controls. We conclude that coronary flow reserve is reduced in patients with coronary artery stenosis or syndrome X due to different levels of coronary artery abnormalities. PMID- 7866907 TI - [Lipid peroxidation injury to red blood cells during extracorporeal circulation: mechanism and protection]. AB - Twelve dogs were subjected to cardiopulmonary bypass with membrane oxygenator for 120 minutes. The effect of lipid peroxide injury on red blood cells was studied by measurement of plasma and erythrocyte membrane lipid peroxide, deformabioity of erythrocyte, plasma free hemoglobin, superoxide dismutase, Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase of erythrocytes. The effect of vitamin E on red blood cells was also investigated. The findings indicated that vitamin E might protect red blood cells from lipid peroxide injury during extracorporeal circulation. The mechanism of damage effect of lipid peroxide and the protective effect of vitamin E on red blood cells were briefly discussed. PMID- 7866908 TI - [Advances in the study of laminin receptors]. PMID- 7866909 TI - Vertebral osteoporosis as painted by Vittore Carpaccio (1465): reflections on paleopathology of osteoporosis in pictorial art. PMID- 7866910 TI - Metacarpal bone mass in normal and osteoporotic Japanese women using computed X ray densitometry. AB - The metacarpal bone mineral density (BMD) and metacarpal index (MCI) of the second metacarpal bone were measured by computed X-ray densitometry (CXD) (Teijin Ltd., Tokyo), which we have established with the development of microdensitometry of radiographs. In this study, we evaluated the basic attributes of this CXD method and determined the age-related changes in both metacarpal measurements in normal Japanese women. The precision in vivo was measured in eight subjects. The precision errors [coefficient of variation (CV)] were 0.2-1.2% CV for metacarpal BMD and 0.4-2.0% CV for MCI, respectively. We have obtained low precision error and more rapid analysis, within 3 minutes respectively, compared with the previous methods. Age-related changes in the metacarpal measurements were evaluated in 1438 normal women. Both measurements showed the most significant decrease in the sixth decade of life. The rate of decrease in the sixth decade was 1.6%/year for metacarpal BMD and 1.5%/year for MCI. On comparison between metacarpal BMD by CXD and spine BMD using dual energy X-ray absorptiometry (DXA) in 248 normal women with and without menstruation, the two measurements were found to be similarly decreased in the subjects within 5 years after menopause. There was also no significant difference in the Z-score between metacarpal BMD and spine BMD within 5 years after menopause. These results indicate that early postmenopausal bone loss occurs not only in the spine but also in the metacarpal bone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866912 TI - The acute metabolic effects of oral tricalcium phosphate and calcium carbonate. AB - A double-blind study was performed to test the metabolic effects of tricalcium phosphate (TP) and calcium carbonate (CC) on serum calcium (SCa), serum phosphorus (SP), and immunoreactive intact serum parathyroid hormone (SPTH) levels in two groups of 24 subjects. The mean age of young subjects was 29.5 years, and elderly subjects, 65.9 years. These subjects fasted overnight for 12 hours, but with good hydration, before the tests. Following a 2-hour baseline urine collection, 1200 mg elemental calcium (as CC or TP in tablet form) was chewed and ingested and 2-hour postload urines were collected. Blood was drawn immediately before and at 1, 2, and 4 hours after calcium load. The results showed that SCa and SP increased, whereas SPTH decreased with both preparations. The increment of SCa was similar after oral load of either calcium salt in both groups. The increment of SP after TP load was more than after CC. The urinary calcium/creatinine ratio (UCa/Cr) increased significantly after both preparations in the young group. The urinary phosphorus/creatinine ratio (UP/Cr) did not change significantly following TP, but decreased significantly after CC load in the young subjects. However, in the elderly individuals, the UP/Cr increased after TP load but did not change following CC, with statistical significance. The difference of urinary cyclic adenosine monophosphate/creatinine ratio (UcAMP/Cr) was not significant in both groups with either preparation. In summary, there was a similar rise in SCa and an equivalent fall in SPTH between TP and CC, in both young and elderly individuals. PMID- 7866911 TI - Influence of age on effects of endogenous 1,25-dihydroxyvitamin D on calcium absorption in normal women. AB - Recent reports of increases in serum 1,25-dihydroxyvitamin D [1,25(OH2)D] concentration with aging despite no changes or decreases in calcium absorption suggest that elderly women have intestinal resistance to vitamin D action. Thus, in 15 young adult (30 +/- 1 year) and 15 elderly (74 +/- 1 year) women (mean +/- SE), we assessed the responsiveness of intestinal calcium absorption to increases in circulating 1,25(OH)2D induced by 4 days of an experimental diet (150 mg calcium and 1600 mg phosphorus daily). True fractional calcium absorption (FCA) (44Ca mixed with food and 42Ca given intravenously, then their ratio in urine measured by mass spectrometry) was determined. Baseline serum intact parathyroid hormone (PTH) concentration was higher in the older women (P = 0.01) whereas serum 1,25(OH)2D concentration and true FCA were similar. In both groups, serum 1,25(OH)2D concentrations increased (P < 0.002) on the experimental diet. After 4 days on the diet, serum 1,25(OH)2D increased over baseline by 30.5 and 35.6% and, despite these increases, true FCA was 40 +/- 3 versus 40 +/- 4%/24 hours (NS between groups) in the young and elderly women, respectively. These data suggest that either elderly women have normal intestinal responsiveness to vitamin D or that the resistance to it is too mild to be detected by these methods. PMID- 7866913 TI - Increasing age-adjusted incidence of hip fractures in Finland: the number and incidence of fractures in 1970-1991 and prediction for the future. AB - Hip fractures in the elderly are a worldwide epidemic, and aging of the populations is increasing the burden of these fractures on the health care systems. To improve the knowledge of whether the number of hip fractures is increasing even more rapidly than can be accounted for by the demographic changes only, all patients who were admitted to Finnish hospitals in 1970, 1975, 1980, 1985, 1988, and 1991 for primary treatment of first hip fracture were selected from the National Hospital Discharge Register. There was a steady, average 7.7% annual increase in the total number of hip fractures in Finland during this period so that the number of fractures was 2239 in 1970 and 6071 in 1991. The proportion of patients aged 60 years or more increased steadily from 75% in 1970 to 91% in 1991. In 1991, 74% of the patients were women. Across the study period, the age-adjusted total incidence of hip fractures also increased in both women and men 50 years of age and over. This increase was more pronounced in men. Thus, the increasing incidence of hip fractures in Finland was not only due to the fact that the population was aging but also due to the increasing age-adjusted incidence. We conclude that the number of hip fractures in Finland is increasing more rapidly than can be accounted for by the demographic changes only and this will seriously challenge the Finnish health care system in the future. PMID- 7866914 TI - Effect of salmon calcitonin on deoxypyridinoline (Dpyr) urinary excretion in healthy volunteers. AB - To evaluate the influence of synthetic salmon calcitonin (SMC) on bone resorption we investigated the modifications in urinary cross-links excretion [pyridinoline (Pyr) and deoxypyridinoline (Dpyr)] induced by a single dose of the drug. The study was carried out in 16 healthy volunteers given a single dose of either 50 IU SMC I.M. or placebo, according to a double-blind, cross-over design. Urine was collected every 24 hours during the 72 hours after each treatment and Pyr and Dpyr were measured by an automated HPLC method. Pyr showed no significant difference after the two treatments, whereas in the first 24-hour urine collection Dpyr (nmol/24 hours +/- SD) was considerably lower after SMC than after placebo (118.9 +/- 26.0 against 147.2 +/- 45.0, P < 0.05). The amount of saved Dpyr was 19.2%. The selective effect of SMC on Dpyr excretion was more evident comparing the Pyr/Dpyr ratios for placebo and SMC during the first day of the study (4.1 +/- 0.6 against 4.8 +/- 0.7, respectively, P < 0.01). Using Eyre's formula (10 nmol Dpyr = 0.17 g bone) and assuming that no Dpyr is metabolized, the mean daily amount of bone resorbed was calculated (2.5 g for placebo and 2.0 g for SMC). The difference is the index of the bone-saving effect of SMC (0.48 g/day, or 19.2%). In conclusion, assuming that in healthy volunteers bone turnover is balanced with equal rates of formation and resorption, a dose of 50 IU I.M. of SMC reduces resorption, with a bone gain in the first 24 hours calculated as 9.4 mg/IU. PMID- 7866916 TI - Demographic aspects of Paget's disease of bone in the Negev of southern Israel. AB - In a mainly retrospective but partly prospective survey of the period 1968-1993 in southern Israel, 61 cases of Paget's disease of bone were identified. Fifty six percent were of non-Afro-Asian origin and 44% originated from Afro-Asia, which is approximately the inverse of the ratio in the local general population. The largest single groups from non-Afro-Asia and Afro-Asia originated, from Romania and Tunisia, respectively, and Australia and Argentina were also disproportionately prominent as countries of origin. Israel itself was the origin of few patients. All the patients were Jews except for one Bedouin Arab, which is far different from the distribution of Bedouins and Jews in both the surveyed area and the hospital population. The differences between these groups numerically and against the background local population may well have been statistically significant had the circumstances enabled greater randomness in the collection of the data analyzed. It is surmised that in southern Israel the prevalence of Paget's disease of bone is about 1%, similar to that in southern Europe. PMID- 7866915 TI - Nocturnal rise in markers of bone resorption is not abolished by bedtime calcium or calcitonin. AB - As assessed by urine pyridinium cross-links, bone resorption increases at night. This has been ascribed to either the nocturnal rise of serum parathyroid hormone (PTH) or immobilization. ICTP is the carboxyterminal telopeptide region of type I collagen in bone, cross-linked via pyridinium cross-links and liberated during the degradation of type I collagen. To study whether the nocturnal rise in bone resorption is seen also in serum type I collagen carboxyterminal telopeptide (ICTP) and whether this rise is abolished by bedtime calcium or calcitonin, nine healthy postmenopausal women participated in three 24 hour sessions. At 2200 hours, either 1 g of oral calcium or 200 IU of intranasal calcitonin or no treatment (control session) were given. The participants were recumbent from 2200 hours to 0600 hours. Like urinary pyridinolines, serum ICTP showed a clearcut nocturnal rise during the control session, increasing from 3.7 +/- 0.3 micrograms/liter (mean +/- SE) at 2000 hours to 4.9 +/- 0.4 micrograms/liter at 0600 hours (P < 0.001). Administration of calcium did not affect either serum ICTP or urinary pyridinolines, although it decreased serum intact PTH by 18% (P < 0.001) as assessed by areas under curve (AUC) after 2200 hours. Serum ICTP and urinary pyridinolines remained unchanged also after administration of calcitonin which increased the AUC for serum intact PTH by 9% (P < 0.05). In conclusion, serum ICTP follows a circadian rhythm in healthy postmenopausal women. The nocturnal rise in markers of bone resorption is not due to PTH, and its dependency on the function of osteoclasts is open to question. PMID- 7866917 TI - Stimulation of human osteoblast differentiation and function by ipriflavone and its metabolites. AB - Ipriflavone (IP), an isoflavone derivative, has been shown to interfere with bone remodeling by inhibiting bone resorption and perhaps stimulating bone formation. In this study, we have analyzed the effect of IP and its metabolites on the differentiation and function of human osteoblastic cells. Bone marrow stromal osteoprogenitor cells (BMC) and trabecular bone osteoblasts (HOB) were isolated from human donors. The former can be induced to differentiate by treatment with dexamethasone, whereas the latter represent a more differentiated osteoblast. Incubation of BMC with metabolite III (10(-5) M) for 1 week induced modest but significant changes of alkaline phosphatase activity. Though both IP and metabolite III stimulated the expression of bone sialoprotein mRNA, a protein involved in cell attachment to the matrix, only metabolite III increased the steady-state level of decorin mRNA, a collagen fibrillogenesis-regulating proteoglycan. Metabolites III and V, but not the other isoflavones, increased the expression of type I collagen mRNA in HOB, whereas no detectable changes were observed in BMC cells with any of the experimental compounds. In HOB, an increased abundance of osteopontin and bone sialoprotein mRNA were also obtained after 1-week treatment with IP or metabolite V. No appreciable effects of IP or its metabolites were seen on osteocalcin expression and synthesis by either cell type. Finally, IP consistently increased the amount of 45Ca incorporated into the cell layer by BMC, and stimulated mineralization of both BMC and HOB, assessed by von Kossa staining. Thus, IP and its metabolites regulate the differentiation and biosynthetic properties of human bone-forming cells by enhancing the expression of some important matrix proteins and facilitating the mineralization process. PMID- 7866918 TI - Differential effects of insulin and insulin-like growth factor-I in the femoral tissues of rats with skeletal unloading. AB - The alteration of bone metabolism in the femur of rats with skeletal unloading for 4 days was investigated. Skeletal unloading was designed using the model of hindlimb hang in rats. Skeletal unloading caused a significant decrease in femoral weight, calcium, and phosphorus contents in the metaphysis but not diaphysis. Also, the unloading induced a significant decrease of zinc content, alkaline phosphatase activity, and deoxyribonucleic acid (DNA) content in the femoral diaphysis and metaphysis. When the femoral-diaphyseal and metaphyseal tissues from normal and skeletal-unloading rats were cultured in the presence of insulin (10(-9) and 10(-8) M) for 24 hours in vitro, the hormonal effect to increase alkaline phosphatase activity and DNA content in the diaphysis, but not metaphysis, was lost in the bone tissues from unloading rats. However, the culture with insulin-like growth factor-I (IGF-I; 10(-8) and 10(-7) M) produced a significant increase of alkaline phosphatase activity and DNA content in both the diaphyseal and metaphyseal tissues from normal and unloading rats. These results demonstrate that skeletal unloading causes an impairment of insulin effect, but not IGF-I effect, on bone metabolism in femoral tissues. PMID- 7866919 TI - Combined magnetic fields increased net calcium flux in bone cells. AB - Low energy electromagnetic fields (EMF) exhibit a large number of biological effects. A major issue to be determined is "What is the lowest threshold of detection in which cells can respond to an EMF?" In these studies we demonstrate that a low-amplitude combined magnetic field (CMF) which induces a maximum potential gradient of 10(-5) V/m is capable of increasing net calcium flux in human osteoblast-like cells. The increase in net calcium flux was frequency dependent, with a peak in the 15.3-16.3 Hz range with an apparent bandwidth of approximately 1 Hz. A model that characterizes the thermal noise limit indicates that non-spherical cell shape, resonant type dynamics, and signal averaging may all play a role in the transduction of low-amplitude EMF effects in biological systems. PMID- 7866920 TI - Contribution of collagen and mineral to the elastic anisotropy of bone. AB - It has long been thought that collagen fibers within the bone matrix are deposited in an aligned pattern that channels mineral growth. If this model of bone structure is correct, both organic and inorganic phases of bone should have similar elastic anisotropy. Using an acoustic microscope, we measured longitudinal and transverse acoustic velocities of cortical specimens taken from 10 dog femurs before and after removal of either the mineral (using 10% EDTA) or collagen phases (using 7% sodium hypochlorite) and calculated longitudinal (CL) and transverse (CT) elastic coefficients. The anisotropy ratio (CL/CT) decreased significantly after demineralization (1.61 before versus 1.06 after, P < 0.0001, paired t-test). However, there was no significant change after decollagenization (1.51 before versus 1.48 after, P = 0.617, paired t-test). We conclude that the orientation of mineral crystals is the primary determinant of bone anisotropy, and the collagen matrix within osteonal bone has little directional orientation. PMID- 7866921 TI - Localization of follistatin, an activin-binding protein, in bone tissues. AB - We have previously reported that activin-A has a mitogenic effect on osteoblast like MC3T3-E1 cells and that these cells produce an activin-binding protein, follistatin (Hashimoto, M., Shoda, A., Inoue, S., Yamada, R., Kondo, T., Sakurai, T., Ueno. N., and Muramatsu, M. (1992) J. Biol. Chem. 267, 4999-5004). Activin-A was also detected abundantly in bone matrix tissues and was found to act as an osteoclast differentiation factor. Here, we studied the expression of follistatin in bone tissues by in situ hybridization with a follistatin cRNA probe. Follistatin transcript was detected in the osteoblasts and a fraction of osteocyte population in the developing mouse mandible. Immunohistochemistry using anti-follistatin antibody supported this observation at the protein level. Follistatin mRNA was also detected in the callus of repairing bone after fracture. These findings suggest that activin and follistatin may play significant roles in the bone system in vivo. PMID- 7866922 TI - Mass-spectrographic analysis of a porcine amelogenin identifies a single phosphorylated locus. AB - The amelogenins of the extracellular matrix of developing dental enamel, comprise a family of tissue-specific proteins which are postulated to play a central role in the biomineralization of dental enamel [1]. The primary structures of amelogenins derived from cow, pig, human, mouse and rat have now been elucidated by the interpretation of cDNA sequences or by direct amino acid sequence determinations [2-6] demonstrating a high degree of sequence homology between species [1]. However, the nature of post-translational modification of these proteins is less clear. In particular, early reports of amelogenin phosphorylation [7-8] have proved to be difficult to confirm by direct chemical analyses [1]. Using mass spectrographic analysis, we recently [9], reported that the lower molecular weight (5-7 kDa) bovine and porcine amelogenin polypeptides (TRAP and LRAP) contained a single phospho-serine residue at position 16Ser and, since these polypeptides are derived by proteolytic processing from the higher molecular weight "parent" amelogenins (18-25 kDa), we concluded that these precursor molecules must also be phosphorylated, as has previously been suggested [10]. In contrast to these observations, an extensive amino acid sequencing study of porcine amelogenins has recently reported no evidence for such phosphorylation [1]. We now report that a new analysis of the major porcine ("20K") amelogenin provides positive evidence for porcine amelogenin phosphorylation. PMID- 7866923 TI - Your goals into action. PMID- 7866924 TI - AIDS and discrimination: the Windsor case. PMID- 7866925 TI - The changing face of dentistry. Interview by Terence Davis. PMID- 7866926 TI - Celebrating 60 years of publication: the Journal of the Canadian Dental Association. PMID- 7866927 TI - Survey of knowledge of infectious disease and infection control practices of dental specialists. AB - A questionnaire was developed to assess the knowledge of clinical specialists regarding infectious disease as well as their infection control practices. The questionnaire was mailed to 202 dental specialists in British Columbia. Seventy per cent returned completed surveys. Their responses indicate that the mechanisms, route and risk of transmission of the viral pathogens of importance in dental practice are not clearly understood. However, infection control practices closely follow the guidelines set forth by the Canadian Dental Association and the licensing bodies, including immunization for hepatitis B (82 per cent), glove use (in 89 per cent of non-surgical and 95 per cent of surgical procedures), and sterilization/disinfection of dental handpieces (94 per cent). Compliance with infection control guidelines was similar to that reported in the United States, where strict enforcement has been instituted. The majority of dental specialists (84-88 per cent) were either treating or willing to provide treatment to patients with infectious disease. Continuing education in the area of infectious disease is needed to improve dentists' understanding of the risk of transmission to dental providers and patients. This will ensure that compliance with infection control recommendations and appropriate patient care practices continue. PMID- 7866928 TI - Effect on plaque removal and gingivitis of a triclosan-copolymer pre-brush rinse: a six-month clinical study in Canada. AB - The effect on plaque removal and gingivitis of using a pre-brush rinse containing 0.03 per cent triclosan (Irgacare MP, Ciba-Geigy Corp.) and 0.125 per cent of a copolymer of polyvinylmethyl ether and maleic acid over a six-month period, versus using a matching placebo pre-brush rinse, was assessed in this clinical study. Subjects were instructed to rinse their mouths for one minute, twice daily (morning and evening), with 15 mL of their assigned pre-brush rinse. Immediately after rinsing, subjects brushed their teeth for 30 seconds using the dentifrice and toothbrush supplied to them at the outset. Subjects were instructed to refrain from any other oral hygiene procedures throughout the duration of the study. Plaque and gingivitis examinations were conducted after three months and again after six months. At the conclusion of the study (six months), the triclosan/copolymer pre-brush rinse demonstrated an advantage of 24.8 per cent for plaque removal and a 22.1 per cent reduction in gingivitis, when compared to the matching placebo pre-brush rinse. These advantages in plaque removal and gingivitis reduction were statistically significant. The six-month effect of the triclosan/copolymer pre-brush rinse was even greater on "the more difficult to brush" surfaces of the teeth, as determined by the use of the Plaque Severity Index and the Gingivitis Severity Index.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7866929 TI - [Hereditary angioedema: a medical condition with dental implications]. PMID- 7866930 TI - A pilot smoking cessation program involving dental offices in the borough of East York, Ontario: an initial evaluation. AB - A Change Of Heart (ACOH)--a heart-health promotion project based in the Toronto borough of East York--devised a tobacco-cessation counselling program for use in dental offices. This protocol was implemented on a pilot basis in dental offices in East York during 1993. Four practices (seven dentists) agreed to incorporate the program into their office routine. The initial evaluation of the program was carried out in a telephone survey one month later. After one month, none of the dentists had incorporated the program into their office routine, citing lack of time, fear of alienating patients and a preference for their own protocol. All respondents indicated they were happy with the contents of the program and expressed a desire for further education about tobacco-cessation counselling. If dentists are to become more involved in tobacco-cessation counselling, it must be perceived by the profession and the public to be a legitimate activity for dentists. To this end, organized dentistry must actively promote continuing education activities related to cessation counselling, incorporate tobacco cessation counselling into the undergraduate dental curriculum, and collaborate with other interested agencies to raise the public awareness of tobacco as an oral health issue. PMID- 7866931 TI - Orthodontics and TMD. PMID- 7866932 TI - Aortic flow velocity indices during upright exercise: reliability and relationship to cardiac output. AB - OBJECTIVE: To determine the intra- and interobserver reproducibility of Doppler derived ascending aortic flow velocity measurements at rest and during upright exercise of increasing intensity; and to determine the relationship between Doppler-derived measurements and cardiac output obtained by the indirect Fick carbon dioxide rebreathing method in the same conditions. SUBJECTS: Twenty young healthy adults participated in the study; eight participated in the first part and 12 in the second. DESIGN: For the intra-observer study, subjects were submitted to three workloads (50, 100 and 150 W) of 5 mins duration on two occasions, seven days apart. The intra-observer reproducibility was determined by two technicians taking the Doppler measurements within 90 s during the steady state of each workload during the first session. The relationship between cardiac output and aortic flow velocities was studied by measuring cardiac output by carbon dioxide rebreathing and flow velocities by continuous wave Doppler ultrasound simultaneously at rest as well as during the last minute of the three workloads (50, 100 and 150 W) of 5 mins duration. RESULTS: The interobserver reproducibility was very good, with r values of 0.87 for peak velocity (PV) and 0.97 for peak acceleration (PA). The intra-observer reproducibility at the seventh day interval showed r values of 0.93 for PV and 0.96 for PA for one of the technicians. PV and PA of the ascending aortic flow correlated well with cardiac output (r = 0.85 and 0.82, respectively, P < 0.01). ANOVA showed that PV and PA increase proportionately with exercise intensity. CONCLUSION: PV and PA of ascending aortic flow are reproducible and reflect changes in left ventricular function during exercise. PMID- 7866933 TI - Cardiovascular risk factors and lipoprotein profile in French Canadians with premature CAD: impact of the National Cholesterol Education Program II. AB - BACKGROUND: Coronary artery disease (CAD) is the major cause of death in Canadian adults. Regional differences in the prevalence of CAD in Canada are due, in part, to differences in cardiovascular risk factor distribution. Two hundred and forty nine patients of predominantly French Canadian descent (greater than 90%), aged less than 60 years (202 men and 47 women) with angiographically documented CAD were examined in a cardiology secondary prevention clinic and their cardiovascular risk factors and lipoprotein cholesterol levels were determined. OBJECTIVES: To determine the prevalence of cardiovascular risk factors in a group of French Canadian subjects compared with subjects screened for the Quebec Heart Health Survey and to determine the impact of the National Cholesterol Education Program II (NCEP II) on screening and treatment of these patients. METHODS: Observation study of free-living subjects with CAD, compared with a reference group. RESULTS: Mean ages were 48.6 +/- 6.8 and 50.6 +/- 6.4 years for men and women, respectively. On average, the patients were on a diet containing approximately 31% of calories as fat, with 9.7% as saturated fats at the time of blood sampling. The mean number of risk factors was the same in men and women (3.5 +/- 1.2 for men versus 3.2 +/- 1.3 for women; P not significant) but their prevalence differed between sexes. Family history of CAD was seen in 78.5% of men versus 77.3% of women (P not significant), smoking (defined as more than 10 cigarettes per day in the year preceding the clinical evaluation) in 45.7% of men versus 41.9% of women (P not significant), a history of smoking in 75.5% of men versus 69.8% of women (P not significant) and diabetes in 14.7% of men and 25% of women (P not significant). There was less hypertension in men (31.4% versus 52.3%, P = 0.015) and fewer men had a low density lipoprotein cholesterol of 3.4 mmol/L or greater (66.8% in men versus 83% in women, P < 0.05). Men, however, had a higher prevalence of reduced high density lipoprotein cholesterol (less than 0.9 mmol/L, 57.4% in men versus 31.9% in women, P < 0.01). Only approximately 5% of premature CAD patients had familial hypercholesterolemia. Compared with a reference group from the Quebec Heart Health Survey, men and women with CAD had a higher prevalence of cardiovascular risk factors. With a cut-off point for total cholesterol of 5.2 mmol/L, 26.2% of men and 17% of women had 'normal' cholesterol levels; of these, 67.9% of men and 25% of women had high density lipoprotein less than 0.9 mmol/L. CONCLUSIONS: French Canadian men and women with CAD have a high prevalence of all cardiovascular risk factors. The patients are representative of the Montreal urban area and findings of the present study may not apply to the Quebec population with respect to the prevalence of risk factors. Under the treatment recommendations of NCEP II, 66.8% of men and 83% of women are candidates for drug therapy of dyslipoproteinemia aimed at reducing low density lipoprotein cholesterol levels. According to these data, cardiovascular risk stratification must be based on a complete lipoprotein profile or misclassification, especially in men, may occur. PMID- 7866934 TI - Detection of silent ischemia adds to the prognostic value of coronary anatomy and left ventricular function in predicting outcome in unstable angina patients. AB - BACKGROUND: Patients with unstable angina are at increased risk of unfavourable outcomes such as myocardial infarction, death and urgent revascularization. Early risk stratification may improve subsequent outcome. Recently the presence and duration (at least 60 mins) of silent ischemia as measured by Holter monitoring has been shown to be of prognostic value. The incremental value of this information over that provided by coronary angiography and assessment of left ventricular function is not known. OBJECTIVE: To determine whether detection of silent ischemia is of independent and additional prognostic significance beyond that provided by the angiographic extent of coronary artery disease and left ventricular dysfunction. METHODS: One hundred and thirty-five unstable angina patients with 24 h of ST segment monitoring in addition to early cardiac catheterization (4 +/- 3 days) were assessed. Eighty-nine patients (66%) had ST segment shift for a total of 593 episodes (mean duration of 18 +/- 30 mins per episode) of which 92% were asymptomatic. Ten patients had a myocardial infarction and six patients died during the hospitalization. In addition, there were 33 urgent revascularization procedures. RESULTS: With the generalized additive logistic model, various clinical variables were assessed for predicting unfavourable outcomes. Duration of ST shift (P = 0.02) was second only to angiographic severity of coronary artery disease (P = 0.004) as a predictor. In the presence of these two variables left ventricular function did not have independent prognostic significance (P = 0.16). Event-free survival curves show that duration of ST shift of at least 60 mins was of incremental value in predicting unfavourable in-hospital outcomes compared with both the extent of coronary artery disease and left ventricular dysfunction. CONCLUSION: In patients with unstable angina, further stratification can be achieved early with Holter monitoring in addition to coronary angiography and assessment of left ventricular function. PMID- 7866935 TI - Molecular analysis provides evidence for human to human transmission of Staphylococcus aureus endocarditis in non-drug abusers. AB - Two cases of invasive Staphylococcus aureus are reported in which human to human transmission resulted in primary bacteremia and endocarditis. The identity of the organism was confirmed by phage typing, antibiograms, coagulase gene polymorphisms and ribotyping. This is the first documented case of such transmission not involving an intravenous drug abuser. PMID- 7866936 TI - Antiphospholipid antibody syndrome associated with large aortic valve vegetation and stroke. AB - An unusual case of an aortic valve mass in a patient with a stroke and primary antiphospholipid antibody syndrome is discussed. The association of cardiac abnormalities and antiphospholipid syndrome is reviewed. PMID- 7866937 TI - Cardiac sarcoidosis: an unforeseen cause of sudden death. AB - Sudden death occurring in a male with established coronary artery disease is inevitably assumed to result from the atherosclerotic process, and an autopsy is rarely requested to confirm the cause. On occasions, however, an autopsy reveals the unexpected, such as cardiac sarcoidosis. PMID- 7866938 TI - Hypoxia preconditions rabbit myocardium by an adenosine receptor-mediated mechanism. AB - OBJECTIVES: To test the ability of hypoxia without reoxygenation to precondition myocardium and to test a possible involvement of adenosine receptors in that response. DESIGN: Isolated rabbit hearts were perfused with oxygenated Krebs Henseleit buffer. Control hearts underwent 30 min regional ischemia followed by 2 h reperfusion. A second group received 10 min global perfusion with hypoxic buffer (PO2 = 33 +/- 3 mmHg) immediately before coronary occlusion. A third group was subjected to a similar protocol as group 2, with the adenosine receptor blocker 8-(p-sulfophenyl) theophylline (SPT) (100 microM) added to the buffer immediately before and throughout hypoxia. At the end of reperfusion the area at risk for infarction was determined by fluorescent particles while infarction size was measured by triphenyltetrazolium staining. RESULTS: Hearts without hypoxic perfusion preceding ischemia experienced 38.2 +/- 2.4% infarction. The hypoxic group, despite a longer total period of oxygen deprivation, had only 21.0 +/- 4.2% infarction (P < or = 0.05). SPT blocked the protection (42.1 +/- 6.9% infarction). CONCLUSIONS: Hypoxia without subsequent reoxygenation before ischemia protected the heart from infarction, indicating that reoxygenation may not be the critical feature of reperfusion typically employed in an ischemic preconditioning protocol. Because adenosine receptor blockade abolishes the protection from hypoxic perfusion, the mechanism of this protection may be similar to that seen with ischemic preconditioning. PMID- 7866940 TI - Proceedings of the 1994 Congress and Scientific Meeting of the Chinese Medical Association. Abstracts. PMID- 7866939 TI - Role of polymorphonuclear leukocytes in reperfusion injury of globally ischemic rat heart. AB - OBJECTIVE: Polymorphonuclear leukocytes (PMNs) have recently been observed to generate oxygen free radical (OFR) species during regional myocardial ischemia reperfusion. This study evaluated the role of PMN-derived OFR in reperfusion injury of globally ischemic rat heart. METHODS: Isolated rat hearts were perfused with recirculating medium as follows: hydrogen peroxide; PMNs; PMNs plus phorbol myristate acetate (PMA); PMNs plus PMA plus OFR scavengers (superoxide dismutase [SOD] plus catalase, preprotection and reperfusion); ischemia-reperfusion (34 degrees C); ischemia-reperfusion (34 degrees C) plus OFR scavengers; ischemia reperfusion (34 degrees C) plus PMNs; and ischemia-reperfusion (34 degrees C) plus PMNs plus OFR scavengers. Left ventricular (LV) systolic (developed pressure [Pmax], +dP/dt) and diastolic (left ventricular end-diastolic pressure [LVEDP], dP/dt, LV compliance, LV wall stiffness) functions were evaluated. LV contracture development was studied by applying the quick stretch test. RESULTS: In vitro hydrogen peroxide perfusion significantly reduced LV contractility and caused a marked increase in LVEDP. PMN-derived OFR (mainly hydrogen peroxide) caused serious derangements in LV systolic and diastolic functions and produced a significant calcium-dependent LV contracture. Ischemia-reperfusion (34 degrees C) in the absence of PMNs produced predictable abnormalities in LV function and caused severe ATP-dependent LV contracture. Ischemia-reperfusion (34 degrees C) in the presence of PMNs significantly enhanced reperfusion injury. LVEDP increased considerably and a condition of irreversible contracture (stone heart) developed. OFR scavengers (SOD and catalase) were effective in preserving LV diastolic function and in neutralizing the additional component of injury caused by in vitro or in situ activation of PMNs. However, OFR scavengers failed to offer any significant improvement in LV systolic functions. CONCLUSIONS: Results of these studies indicate that: first, activated PMNs produce significant amounts of hydrogen peroxide; second, OFR released by activated PMNs during perfusion caused a significant depression of LV systolic and diastolic function; third, PMNs enhanced reperfusion injury of the globally ischemic rat heart; and fourth, the OFR scavengers SOD and catalase minimized changes in LV diastolic function, whereas LV systolic function showed little improvement. PMID- 7866941 TI - Comparative dermatology: a historical overview. PMID- 7866942 TI - Histologic features of normal canine and feline skin. PMID- 7866943 TI - Cutaneous lymphomas in companion animals. PMID- 7866944 TI - Pigmented lesions of the skin. PMID- 7866945 TI - Comparative pathology of pemphigus in dogs and humans. PMID- 7866946 TI - Cutaneous drug eruptions with epidermal necrosis: a discussion of pathophysiologic and comparative aspects. PMID- 7866947 TI - Fungal diseases. PMID- 7866948 TI - Comparative dermatology: parasitic disorders. PMID- 7866949 TI - Seborrheic skin disorders and their treatment in dogs. PMID- 7866950 TI - Food allergy. PMID- 7866951 TI - Atopic dermatitis. PMID- 7866952 TI - Diseases of the foot and nails: humans, cats, and dogs. PMID- 7866953 TI - Retinoids in veterinary dermatology. PMID- 7866955 TI - Veterinary conference proceedings database. PMID- 7866954 TI - CO2 laser surgery in veterinary dermatology. PMID- 7866956 TI - Veterinary practice owners' association. PMID- 7866957 TI - Dog bite litigation--a matter of commonsense? PMID- 7866958 TI - An ethicist's commentary on the case of the ewes in distress. PMID- 7866959 TI - Bacterial and fungal flora in healthy eyes of birds of prey. AB - Birds of prey are often affected with external ocular injuries that are routinely treated with antimicrobial agents used for small animals. The resident ocular bacterial and fungal flora is still unknown in birds of prey and this knowledge would be very useful in assessing the accuracy of treatments. In a study involving 65 raptors with healthy eyes, swabs were taken from both eyes to identify the resident bacterial and fungal flora. Fifty-five birds had a positive culture in one or both eyes. Both gram-positive and gram-negative organisms were isolated, with a predominance of Staphylococcus spp., which were found in 52.3% of cultures. Only two fungal species, Aspergillus spp. and Cladosporium spp. were found. The overall results of this study are similar to previous studies carried out in humans and other animals. PMID- 7866960 TI - Evaluation of two supplements for the prevention of alfalfa bloat. AB - Poloxalene and a mineral mixture feed supplement patented for the treatment of emphysema, polyarthritis, and other pectin related diseases were tested in two trials for their ability to prevent bloat in cattle fed fresh alfalfa. Each trial had a crossover design using three Jersey steers with rumen fistulas per group. Each trial period continued until the total number of cases of bloat reached > or = 24. Treatments were given at 0800 each day. The mineral mixture was given at 100 g/d and 190 mg/kg body weight per day in the first and second trials, respectively. Poloxalene, which was tested only in the second trial, was given at 23 mg/kg body weight per day. Each group of steers was then fed 200 kg of freshly harvested alfalfa in the vegetative to early bloom stages of growth at 0830. In the first trial, only 69% as many cases of bloat occurred on the mineral mixture as on the control treatment, but no significant difference was detected in the second trial. The potency of the alfalfa may have been higher in the second trial, when forage dry matter was lower, magnesium and soluble nitrogen were higher, and bloat occasionally occurred twice a day. Bloat did not occur when the steers were treated with poloxalene. In these trials, poloxalene was completely effective in preventing bloat, but the mineral mixture was only partially so. PMID- 7866961 TI - Hematological and clinical responses to combined mitoxantrone and cyclophosphamide administration to normal cats. AB - The purpose of this study was to examine the feasibility of a combination chemotherapy protocol ("CYCLONE") in cats, utilizing mitoxantrone and cyclophosphamide. Three normal adult cats were administered mitoxantrone (6.5 mg/m2 intravenously) and cyclophosphamide (100 mg/m2 intravenously) every 21 days for a total of three doses. Individual white blood cell count nadirs (range, 2.0 9.5 x 10(9)/L) and neutrophil count nadirs (range, 0.3 to 5.0 x 10(9)/L) occurred between days 2 and 10 after each dose of chemotherapy. Mean white blood cell count nadirs (range of mean, 5.5 to 8.4 x 10(9)/L) occurred between days 6 and 8, as did the mean neutrophil count nadir (range of mean, 1.7-4.0 x 10(9)/L). Side effects were limited to transient appetite suppression in one cat and loose stools in two cats. Myelosuppression and gastrointestinal side effects were comparable to those observed with single-agent mitoxantrone protocols. Further investigation of this protocol is warranted. PMID- 7866962 TI - Semen embolism in the lungs of a young ram. PMID- 7866963 TI - Cysticercus bovis in cattle in two beef feedlots in southern Ontario. PMID- 7866964 TI - Hypocalcemia in a herd of aged beef cows. PMID- 7866965 TI - Severe psoroptic mange and endoparasitism in a Nubian doe. PMID- 7866966 TI - Critical thinking: benefits of presurgical thoracic screening. PMID- 7866967 TI - Management of canine epilepsy with phenobarbital and potassium bromide. PMID- 7866968 TI - A business plan you can bank on. PMID- 7866969 TI - Multiple intussusceptions in a puppy. PMID- 7866970 TI - Diagnostic ophthalmology. Orbital mast cell neoplasia. PMID- 7866971 TI - The Robert Tiffany lectureship. Always some certain end must be kept in view (semper aliquid certi propendum est). PMID- 7866972 TI - Patient-related barriers to cancer pain management in Taiwan. AB - The reluctance of patients with cancer to report pain and to use analgesics hinders the management of their pain. In the United States, this reluctance is related to the patient's misconceptions regarding addiction and tolerance to analgesics and the desire to be a "good patient" who does not complain. Reports in the literature suggest that patients in Taiwan may have these same concerns and misconceptions. This study was designed to explore (a) the concerns of patients in Taiwan about reporting pain and using analgesics and (b) the relationship between these concerns and the adequacy of analgesics used by the patients. Sixty-three patients with cancer completed the Barriers Questionnaire Taiwan (BTQ) form, a self-report instrument that measures the extent to which patients have eight specific concerns about reporting pain and using analgesics. The responses indicated that patients who were less educated were more likely to have concerns and that patients in general were most worried about tolerance. Patients who were inadequately medicated, as determined by an index of "adequate pain management" constructed for the study, had significantly higher levels of concerns. Open communication between health professionals and patients and educational programs about pain and about the concerns measured in this study could help overcome these concerns and misconceptions and improve pain management. PMID- 7866973 TI - Fatigue-reducing strategies used by patients receiving treatment for cancer. AB - In order to determine which strategies are most effective in relieving fatigue of women undergoing treatment for cancer, women receiving either chemotherapy (n = 45) or radiation therapy (n = 54) were interviewed twice to determine their level of fatigue and the effectiveness of the strategies they used to relieve their fatigue. The subjects were interviewed either at the start and mid-point of any cycle of chemotherapy, or at the beginning and end of a 5- or 6-week course of radiation therapy. At each interview, the subjects completed the Pearson Byars Fatigue Feeling Checklist and the Fatigue Relief Scale. At the second interview, the patients were significantly more fatigued than they had been at the first interview (p < 0.0001). The more effective the fatigue-relieving strategies at the second interview, the less fatigue experienced by the women (p < 0.0001). At both interviews, subjects used similar strategies to relieve their fatigue. Sleep and exercise were among the most effective strategies. However, there was a wide range of scores for each strategy used, indicating variability among subjects as to the effectiveness of the strategy. The results of the study provide nurses with some guidance as to strategies they might suggest to patients who experience fatigue. PMID- 7866974 TI - Variables associated with breast self-examination among Chinese women. AB - Asians are the fastest growing minorities in the U.S. To deliver culturally sensitive care is a significant challenge to the nursing profession. Research identifying variables associated with breast self-examination (BSE) in the U.S. has been conducted on Caucasian women, but little is known about Asian women. Based on the health belief model (HBM) and Bandura's social learning theory, the purpose of this study was to identify barriers to the practice of BSE among Chinese women. The Chinese women (n = 174; mean age, 31 years) were surveyed with a 38-item, five-point Likert scale developed by Champion, and Lauver and Angerame, as well as a six-step accuracy check. The factors included susceptibility; seriousness for breast cancer; general efficacy for BSE; specific efficacy of BSE for oneself; competence; comfort; and control. The results showed that only 15% of these Chinese women practiced BSE monthly, and 48% reported never having performed BSE. Approximately 50% had no opinion on perceived susceptibility to and seriousness of breast cancer; nevertheless, > 80% recognize the efficacy of BSE. Perceived competence significantly accounted for 10% of the variance on BSE frequency (p < 0.001). Implications for nursing interventions that foster competence in BSE for this population are suggested. The study also demonstrates culturally specific methodological considerations. PMID- 7866975 TI - Breast cancer survivors: concerns and coping. AB - With 5-year cancer survival rates increasing and breast cancer appearing in one of eight women in the United States, health-care providers need to become aware of issues common to this population. Knowledge of coping strategies can be used to improve the lives of survivors. This descriptive study used a semistructured interview to delineate concerns and coping as perceived by 14 women who had lived at least 5 years after a diagnosis of breast cancer. Informants gave evidence of a survivor personality as they described the use of multiple coping strategies, with information-seeking, work, spirituality, and family being predominant. The majority indicated that awareness of vulnerability had effected changes in how they viewed life. Their major concern was fear of recurrence. These women made adjustments to living with cancer and were able to describe positive aspects of their cancer experiences. PMID- 7866976 TI - Perceptions of the mammography experience. AB - The 1993 projections for breast cancer indicate a morbidity of 183,000 women with a mortality rate of 18%. Mammography is one of three approaches available for the early detection of breast cancer. However, underutilization has been reported and attributed to pain associated with the procedure, the expense to the consumer, and lack of referral by physicians. Other reasons for the low utilization rates include fears on the part of the woman of a positive diagnosis, radiation, and a possible mastectomy. This study provides an analysis of the responses of a convenience sample of 272 women, aged 30-90 years, to two open-ended questions about the mammography experience. The words and phrases women used to describe the mammography experience and the sensations experienced in their breasts during mammography were subjected to content analysis. The results of this study suggest that the word descriptors women use to describe their experience during mammography are highly individualistic and may not be totally captured by numeric or descriptive rating scales of pain intensity. PMID- 7866977 TI - Development of a benefits and barriers scale for mammography utilization. AB - The purpose of this study was to refine scales to measure Health Belief Model concepts of benefits and barriers using the context of mammography screening. Both scales used a summated Likert format with five response options. Items were first subjected to content analysis by national experts. Data were then collected from a random sample of 581 women who were 35 years or over. Retest data were gathered on a subset of women approximately 4-6 weeks later. Construct validity was established using confirmatory factor analysis and exploratory factor analysis with results confirming independence of constructs. Construct validity was also tested by developing hypotheses based on theoretical relationships. Cronbach alpha reliability coefficients for the benefits scale was 0.79 and for the barriers scale was 0.73. Suggestions for further revisions are offered. PMID- 7866978 TI - Use of relaxation to reduce side effects of chemotherapy in Japanese patients. AB - Nausea and vomiting have been recognized as the most distressing side effects of chemotherapy, and are experienced by 66-91% of chemotherapy patients in Japan. Relaxation measures have been used for patients with various other diagnoses, but this technique has never been applied to patients receiving cancer chemotherapy. This pilot study examined the effects of progressive muscle relaxation (PMR) to reduce nausea, vomiting, and anxiety associated with chemotherapy in Japanese patients. Data for eight subjects who were randomly assigned to a treatment group or a control group were analyzed. Both treatment and control groups showed decrease in nausea and vomiting; therefore, the effect of PMR was not verified. However, there was an average decrease of 2.5 points in state-anxiety scores in the treatment group. In addition, some positive effects of PMR were shown by the subjects in the treatment group. PMID- 7866979 TI - Potential long-term and late effects from radiation therapy. AB - This is the sixth of seven self-learning modules that will review radiation therapy. The focus of this module is potential long-term and late effects related to radiation therapy. The module will provide useful information to nurses and other health-care professionals who care for cancer patients or who wish to have a better understanding of radiation therapy. This module will focus on lymphedema, myelopathy, brachial plexopathy, osteoradionecrosis, and other site specific effects. The potential long-term and late effects are rare, but it is important for nurses to be aware of them. PMID- 7866980 TI - Coaching persons with lung cancer to report sensory pain. Literature review and pilot study findings. AB - Because clinicians often do not recognize that patients have pain and patients do not spontaneously communicate their pain, clinicians may fail to prescribe or administer adequate pain medications. One method of improving clinicians' assessments of pain is to coach patients to communicate their pain in ways that clinicians recognize. The aims of our pilot study were to (a) examine the feasibility of implementing a randomized clinical trial of a COACHING protocol in 18 outpatients with lung cancer pain and (b) estimate the effects of COACHING on nurses' knowledge of patients' pain location, intensity, quality, and pattern. The expectation was that COACHING would show a trend toward reducing the discrepancy between patients self-report of sensory pain and sensory pain data known to nurse clinicians. Patients were randomly assigned to be COACHED or NOT COACHED (usual care) and pretest-posttest measures with the McGill Pain Questionnaire (MPQ) and Visual Analogue Scale (VAS) were taken from nurses and patients. Patients- and nurse-completed MPQs and VASs were compared for agreement. Improvement in percent agreement occurred consistently more often (pretest to posttest) between patient self-report of sensory pain and nurses' pain assessments in the COACHED group than in the NOT-COACHED group. Pilot study findings demonstrated feasibility of implementing the COACHING protocol and suggest that COACHING may be effective in reducing discrepancies between patients' self-reports and nurses' assessments of sensory pain. Design modifications are recommended for implementation of future studies. PMID- 7866981 TI - Loss of heterozygosity of the BRCA1 and other loci on chromosome 17q in human prostate cancer. AB - A putative tumor suppressor gene, the BRCA1 gene, on chromosome 17q21 has recently been identified and shown to be mutated in breast and ovarian cancers. We have undertaken the present study to explore the possible involvement of the BRCA1 and/or other potential genes on chromosome 17q in prostate cancer. Twenty three patients were screened by PCR for loss of heterozygosity at five microsatellite loci spanning the region of 17q12-21. One of the loci (i.e., D17S855) studied is intragenic to the BRCA1. Forty-four and 40% of the informative cases showed loss of heterozygosity at the BRCA1 (D17S855) and D17S856 loci, respectively, whereas 10%, 10%, and 11% of the informative cases were positive for loss of heterozygosity at the D17S250, D17S579, and D17S588 loci, respectively. Overall, 52% (11/21) of the informative cases have allelic loss of at least one locus on chromosome 17q. Our data suggest that the BRCA1 and/or other genes within the interval between BRCA1 and D17S856 on 17q21 may be important in the pathogenesis of prostate cancer. PMID- 7866982 TI - Loss of the metastatic phenotype in murine carcinoma cells expressing an antisense RNA to the insulin-like growth factor receptor. AB - The ability of malignant cells to form metastases in secondary sites remains a major obstacle to the curative treatment of cancer. Previously, we identified type 1 insulin-like growth factor (IGF-1) as a paracrine mitogen for highly metastatic murine carcinoma, H-59 cells. Here the role of IGF-1 and its receptor (IGF-1R) in metastasis was further investigated using H-59 cells transfected with a plasmid vector expressing IGF-1R cDNA in the antisense orientation. The transfectants had a markedly reduced expression of IGF-1R and lost the ability to respond to IGF-1 in vitro. When injected in vivo, either directly into the microvasculature of the liver or lung (experimental metastasis) or s.c. to allow the growth of primary local tumors (spontaneous metastasis), these cells did not give rise to any metastases under conditions which allowed wild-type or control transfectants to form multiple hepatic and pulmonary metastases. The results demonstrate that the IGF-1R can play a critical role in the regulation of carcinoma metastasis. PMID- 7866983 TI - Comparative genomic hybridization detects novel deletions and amplifications in head and neck squamous cell carcinomas. AB - To gain a better understanding of genetic changes in squamous cell carcinomas of the head and neck we used comparative genomic hybridization for the analysis of 13 primary tumors. Copy number increases were most frequently observed on chromosomes 3q (10 cases) and 5p (8 cases) and less frequently on 1q (4 cases), 2 (1 case), 7 (2 cases), 8q (2 cases), 9 (1 case), 10p (2 cases), 13q (2 cases), 14q (1 case), 16 (1 case), 17 (2 cases), 20p (2 cases), 21q (1 case) and 22q (1 case). Copy number decreases occurred most frequently at 3p (5 cases), 5q (4 cases), 19p (6 cases), and 19q (5 cases). Copy number decreases also were observed on 1p (2 cases), 2q (2 cases), 4p (2 cases), 4q (2 cases), 7q (2 cases), 8p (1 case), 10q (1 case), 11p (2 cases), 11q (3 cases), 13q (3 cases), 14q (1 case), 16p (1 case), 17p (3 cases), 17q (1 case), 18q (1 case), and 22 (2 cases). Eight sites exhibiting significant sequence amplification were mapped to 3q26- >qter (3 cases), 11q13 (2 cases), 12p (2 cases), 2q33-36 (1 case), 7q21-22 (1 case), 7q33-->qter (1 case), 9p (1 case), and 13q32-->qter (1 case). Our data suggest that the regions 3q26-->qter and 5p may harbor oncogenes important for initiation or progression of squamous cell carcinomas of the head and neck. In addition, comparative genomic hybridization defines a subgroup of tumors with 11q13 involvement, the location of the PRAD1/(CCND1)/cyclin D1 gene. PMID- 7866984 TI - Insulin-mediated intracellular targeting enhances the photodynamic activity of chlorin e6. AB - Photodynamic therapy has been applied quite extensively over the last few years, whereby the activation of photosensitizers by light causes the production of reactive oxygen species such as singlet oxygen, which is cytotoxic. The goal of this study was the enhancement of the photodynamic activity of photosensitizers through their delivery to specific, sensitive intracellular compartments of target cells. We synthesized a BSA-insulin-chlorin e6 conjugate that bound specifically to the insulin receptors (EC50, 1 nM) of the human hepatoma cell line PLC/PRF/5 and could be internalized by receptor-mediated endocytosis. Photodynamic activity, as assessed by various tests, indicated EC50s at about 100 times lower concentrations of conjugate compared to free chlorin e6 itself; and lower doses of irradiation were necessary to activate the conjugate compared to free chlorin e6. Inhibition of endocytosis of the conjugate abrogated the enhanced photodynamic activity of the conjugate above that of free chlorin e6. Endocytosis and subsequent localization around and in the cell nucleus of the BSA insulin-chlorin e6 conjugate could be visualized using both FITC-labeled conjugate and 2',7'-dichlorofluorescin diacetate, a fluorescent indicator of the production of active oxygen species due to chlorin e6 activation. It was concluded that photodynamic activity of the conjugate is higher than that of free chlorin e6 through its receptor-mediated delivery into sensitive intracellular compartments. PMID- 7866985 TI - Radiolabeled antibody combined with external radiotherapy for the treatment of head and neck cancer: reconstruction of a theoretical phantom of the larynx for radiation dose calculation to local tissues. AB - We propose to use radiolabeled antibodies in combination with external beam radiotherapy to improve locoregional control of head and neck cancer. In this case radiation toxicity to mucosa may become a dose-limiting factor and a calculation of the possible compensatory decrease to the external beam radiotherapy would be needed. For this purpose, the following theoretical phantom of a representative organ of this anatomic region, the larynx, was reconstructed and local dosimetric data were derived for a selection of beta-emitting isotopes. The phantom was reconstructed as cylindrical concentric tubes using the established values of an outer diameter of 38 mm and a height of 44 mm. Published mean adult larynx weight (28 g) and cartilage weight (14.7 g) were used. Mean mucosa weight from 5 mucosa samples of our patients was calculated to be 2.0 +/- 0.4 (SD) g. The remaining weight was apportioned to a fat/muscle compartment (11.3 g). The specific gravity of cartilage (1.10 g/cm3), mucosa (1.04 g/cm3), and fat/muscle (1.04 g/cm3) were used to cross-check the volume/mass disparity of the theoretical tubular tissue shells. The established maximum glottic diameter of 24 mm was used to calculate the central air column volume. Mean laryngeal tumor volume from 8 representative laryngeal tumors was 4.4 +/- 3.1 cm3. Tissue compartment thickness was 660 microns for mucosa, 3100 microns for muscle/fat, and 3320 microns for cartilage. These values allowed the calculation of dose absorbed fractions for a number of theoretical radioimmunoconjugates by extending the established calculation of absorbed fractions for spheres of known diameter to absorbed fractions of tissue planes (annuli) of known thickness. We calculated a Deq for the respective tissues in the larynx for 131I-, 186Re-, 188Re-, 67Cu-, 90Y-, and 153Sm-labeled HMFG1. Compensatory decrease to the external radiotherapy dose is 1.1 Gy for each injection of the radioimmunoconjugate we propose to use (131I-HMFG1). This would be best implemented through the modification of the external radiotherapy fractions falling within 2 effective half-lives of this radioconjugate in the mucosa. PMID- 7866986 TI - Adenomas induced by polycyclic aromatic hydrocarbons in strain A/J mouse lung correlate with time-integrated DNA adduct levels. AB - The induction of DNA adducts and adenomas in the lungs of strain A/J mice has been investigated following the single i.p. administration of each of the following polycyclic aromatic hydrocarbons (PAH): pyrene, dibenz[a,h]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, 5-methylchrysene, and cyclopenta[c,d]pyrene. DNA adducts were measured by 32P-postlabeling at times between 1 and 21 days following injection, while adenomas were counted at 240 days after treatment. Pyrene did not induce either DNA adducts or lung adenomas at any of the doses examined. Each of the remaining PAH induced both adenomas and DNA adducts in a dose-dependent manner, with dibenz[a,h]anthracene > 5 methylchrysene > cyclopenta[c,d]pyrene > benzo[a]pyrene > benzo[b]fluoranthene. DNA adducts reached maximal levels between 3 and 9 days after injection, followed by a gradual decrease. The time-integrated DNA adduct level (TIDAL) was calculated by numerically integrating the areas under the adduct persistence curves extrapolated to 240 days for each PAH at each dose level. This value represents the effective total molecular dose of PAH that was delivered to the lung DNA over the entire course of tumorigenesis. A strong correlation of lung adenoma induction with the TIDAL values was observed for each PAH. The slopes of the tumors versus TIDAL value relationships were essentially identical for 5 methylchrysene, cyclopenta[cd]pyrene, benzo[a]pyrene, and benzo[b]fluoranthene. The slope of this relationship for dibenz[a,h]anthracene was markedly greater. The essentially identical induction of adenomas as a function of TIDAL values for these PAH suggests that the formation and persistence of DNA adducts determines their carcinogenic potency. PMID- 7866987 TI - Potential genoprotective role for UDP-glucuronosyltransferases in chemical carcinogenesis: initiation of micronuclei by benzo(a)pyrene and benzo(e)pyrene in UDP-glucuronosyltransferase-deficient cultured rat skin fibroblasts. AB - UDP-glucuronosyltransferases (UGTs) are cytoprotective and may also be genoprotective. Since over 10% of the population have hereditary deficiencies in UGTs, this family of enzymes could constitute an important determinant of susceptibility to chemical carcinogenesis, teratogenesis, and neurodegeneration. Fibroblasts contain Phase I and II drug-metabolizing enzymes, including UGTs, and undergo mitosis, rendering them susceptible to xenobiotic genotoxicity associated with micronucleus formation, which is thought to reflect carcinogenic initiation. Accordingly, skin fibroblasts may provide an accessible model for elucidating genoprotective mechanisms in both animals and humans and for characterizing the potential role of UGTs as determinants of individual toxicological susceptibility. To test this hypothesis, the carcinogen/teratogen benzo(a)pyrene [B(a)P], or its noncarcinogenic B(e)P isomer, was incubated with cultured skin fibroblasts obtained from male RHA-J/J rats. These rats have a hereditary homozygous deficiency in bilirubin UGT and demonstrate reduced xenobiotic glucuronidation, enhanced cytochrome P-450-catalyzed bioactivation, covalent binding, and toxicity of acetaminophen and B(a)P. Control fibroblasts were cultured from UGT-normal congenic homozygous male RHA-(+/+) rats and male Wistar rats. The cells were incubated with 10 microM B(a)P or B(e)P either for assessment of micronucleus formation or for quantifying the bioactivation and covalent binding of B(a)P and the glucuronidation of its hydroxylated metabolites. Compared to control fibroblasts incubated only with buffer, micronucleus formation was not enhanced by either DMSO vehicle or B(e)P. In contrast, B(a)P significantly enhanced micronucleus formation in all cells, and UGT-deficient cells (RHA-J/J) had a > 2-fold higher B(a)P-initiated micronucleus formation compared to UGT-normal cells (RHA-(+/+)) (P < 0.05). Glucuronidation of total B(a)P metabolites was 10% lower in RHA-J/J UGT-deficient fibroblasts, and the covalent binding of B(a)P to protein, reflective of an electrophilic reactive intermediate and DNA-alkylating agent, was up to 3-fold higher in RHA-J/J UGT deficient fibroblasts or fibroblast homogenates compared to UGT-normal controls (P < 0.05). In fibroblast homogenates, addition of the UGT cosubstrate UDP glucuronic acid reduced B(a)P covalent binding, corroborating the cytoprotective importance of UGTs. There was a highly significant correlation between decreasing glucuronidation of B(a)P metabolites and increasing bioactivation and covalent binding of B(a)P (r = -0.889; P = 0.018) in fibroblasts from RHA-J/J and RHA (+/+) rat strains, indicating an important genoprotective role for UGT. These results provide the first evidence that hereditary UGT deficiencies may enhance susceptibility to chemical carcinogenesis and suggest that skin fibroblasts may provide a useful and highly sensitive model for human risk assessment. PMID- 7866988 TI - Metabolism of polycyclic aza-aromatic carcinogens catalyzed by four expressed human cytochromes P450. AB - The role of human cytochromes P4501A1, -1A2, -3A4, and -3A5 in the metabolism of the polycyclic aza-aromatic hydrocarbons 7-methylbenz(c)acridine and dibenz(aj)acridine was investigated. The regioselectivity of the reactions was determined, as well as the associated stereoselectivity in the production of dihydrodiol metabolites and K-region oxides. Metabolite distributions were also examined in the presence of the epoxide hydrolase inhibitor 1,1,1 trichloropropylene-2,3-oxide and the P450 modulator alpha-naphthoflavone. P4501A2 was most regioselective for the production of the proximate carcinogen; the 3,4 dihydrodiol of 7-methylbenz(c)acridine and P4503A4 showed the highest regioselectivity for K-region oxidation. In contrast, the analogous putative proximate carcinogen of dibenz(aj)acridine was formed with the highest relative abundance by P4503A4, while P4501A2 was most regioselective for K-region oxidation. For both compounds the proximate carcinogens possessed predominantly the 3R,4R-absolute configuration, independent of the P450 catalyzing the reaction. The K-region dihydrodiols of 7-methylbenz(c)acridine were formed with no stereoselectivity, except with P4501A2 which favored production of the S,S isomer. In contrast the K-region dihydrodiol of dibenz(aj)acridine was formed by P4501A1 and P4501A2 as the R,R isomer with almost 100% optical purity. P4501A2 and 3A4 showed no stereoselectivity in the formation of the K-region oxide of 7 methylbenz(c)acridine, while P4501A1 produced the 5R,6S-oxide with low optical purity. For dibenz(aj)acridine 5,6-oxide, P4501A1 predominantly formed 5S,6R oxide (80% pure). These results emphasize the importance of the composition and levels of expressed P450s of an individual in relation to the activation and detoxification of toxicants. PMID- 7866990 TI - Idoxifene: report of a phase I study in patients with metastatic breast cancer. AB - Idoxifene, a novel antiestrogen with reduced estrogenic activity when compared to tamoxifen, has been given to 20 women with metastatic breast cancer, 19 of whom had received tamoxifen previously, in doses between 10-60 mg. Idoxifene had an initial half-life of 15 h and a terminal half-life of 23.3 days. At a maintenance dose of 20 mg, a mean steady-state level of 173.5 ng/ml was achieved. Significant falls in luteinizing hormone and follicle-stimulating hormone were seen, but the falls were not dose related. Idoxifene was well tolerated, with 11 patients complaining of mild symptoms similar to those seen with tamoxifen. Fourteen patients continued idoxifene therapy for 1-56 weeks; 4 patients showed stabilization of disease for 6-56 weeks and 2 patients showed a partial response. PMID- 7866989 TI - Pharmacokinetics, biodistribution, and dosimetry of specific and control radiolabeled monoclonal antibodies in patients with primary head and neck squamous cell carcinoma. AB - The pharmacokinetics, biodistribution, and dosimetry of an IgG1 radiolabeled anti mucin mAb (HMFG1) and an isotype-matched control (4D513) were studied in 29 patients with primary head and neck squamous cell carcinoma. Patients were given injections at 3 fixed time points prior to surgery, i.e., 24 (n = 12), 48 (n = 9), or 72 (n = 8) h. They were subsequently classified into two groups based on their immunohistochemical positivity for polymorphic epithelial mucin. Fourteen patients (48%) were positive, 5 of which were studied with both antibodies; and 15 patients were negative (52%), 7 of which were studied with both antibodies. There was no significant difference in serum pharmacokinetics and cumulative urinary clearance of the two antibodies. There was no significant difference in overall normal tissue uptake of specific and control antibody; however, when each component of the normal tissue category was analyzed individually, there was a significantly increased uptake of HMFG1 in mucosa as compared to control antibody. Immunohistochemical studies revealed positive staining of mucosa with HMFG1. There was significantly increased uptake of specific antibody in antigen positive tumors as compared to uptake of control antibody (P < 0.02). A tendency for less label loss over time from positive tumors as compared to control was documented. Absolute antibody uptake and tumor/normal tissue ratios demonstrated significant overlap in individual patients from each category depending on the specific ratio (e.g., tumor/adipose tissue) or time point studied; hence arbitrary cutoff values could not be recommended as indicators of specific uptake. Specificity and localization indices were the most reproducible indicators of specific localization. Areas under the curve were calculated for all tissues, and local dosimetry for the two beta-emitting isotopes 131I and 90Y is presented. The Deq values for antigen-positive tumors were 2.9 cGy/mCi for 131I and 9.0 cGy/mCi injected for 90Y. For antigen-negative tumors these values were significantly lower at 0.83 and 2.4 cGy/mCi of 131I and 90Y, respectively. Bone marrow Deq was calculated to be 0.87 cGy/mCi of 131I-HMFG1 injected. Because the purpose of our ongoing research is to assess the therapeutic potential of the combination of radiolabeled antibody and external radiotherapy, detailed dose calculation to local dose-limiting tissues is required. Deq to mucosa was calculated to be 1.1 and 3.8 cGy/mCi of injected 131I and 90Y, respectively. We conclude that a 9-10-Gy dose increment may be achieved in two administrations of 150 mCi of 131I-HMFG1 during a course of external radiotherapy. This may lead to improved control of local disease in patients with head and neck cancer. PMID- 7866991 TI - In vitro cytotoxicity of a novel antitumor antibiotic, spicamycin derivative, in human lung cancer cell lines. AB - Spicamycin (SPM), produced by Streptomyces alanosinicus, induces potent differentiation in a human leukemia cell line, HL60. One of the derivatives of SPM (SPM-D), KRN5500, has a wide range of antitumor activity against human cancer cell lines. We examined the cytotoxicity of SPM-D in small and non-small cell lung cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony assays. SPM-D was active against a wide range of lung cancer cell lines. All three cisplatin (CDDP)-resistant cell lines established in our laboratory (PC-9/CDDP, PC-14/CDDP, and H69/CDDP) showed collateral sensitivity to SPM-D with relative resistance values of 0.43, 0.34, and 0.32, respectively. Intracellular SPM-D in PC-14/CDDP was 35% higher than that for PC-14 suggesting that intracellular accumulation can explain the collateral sensitivity to SPM-D at least in PC-14/CDDP. On the other hand, in PC-9/CDDP cells, no increase of intracellular SPM-D accumulation was observed, but the conversion ratio of a metabolite (the amino nucleoside moiety of spicamycin binding with glycine, SAN G) from SPM-D evaluated by TLC was higher as compared with that of parental PC-9 cells (45.5% versus 37%; PC-9/CDDP versus PC-9). The increased intracellular metabolism of SPM-D could explain the mechanism of collateral sensitivity in PC 9/CDDP cisplatin-resistant cell lines. To elucidate the determinant of the SPM-D induced cytotoxicity, we established SPM-D-resistant cell lines, PC-9/SPM-D, PC 14/SPM-D, and H69/SPM-D, by exposing cells to stepwise increases in SPM-D concentration. The relative resistances of these sublines were more than 5000, 46.6, and 37.8 times those of the parental cell lines, respectively. The intracellular concentration of the active metabolite, SAN-G, was found to be decreased in the SPM-D-resistant sublines. This result indicates that the intracellular metabolism of SPM-D to SAN-G is one of the determinants of cellular sensitivity to SPM-D in these SPM-D-resistant cell lines. In conclusion, both drug accumulation and metabolism may contribute to the sensitivity/resistance to SPM-D and both may merit investigation. PMID- 7866992 TI - Adenovirus-mediated gene therapy for human head and neck squamous cell cancer in a nude mouse model. AB - Adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir administration was used to treat human head and neck cancer in nude mice. Tumors were generated by transcutaneous needle injection of 6 x 10(6) human squamous carcinoma cells into the floor of the mouth. After 14 days, 10(10) particles of a replication-defective recombinant adenovirus containing the herpes simplex virus thymidine kinase gene (ADV/RSV-tk) were injected directly into the tumors. The mice subsequently received ganciclovir injections for six consecutive days and were sacrificed at 21 days post tumor cell implantation. Clinical response to the treatment was assessed by computer imaged morphometric analysis of cross sectional area of nonnecrotic tumor and mitotic activity, which were used for the calculation of a tumor index. The median tumor index value of the treatment group was 280- to 2400-fold smaller than controls which did not receive the therapeutic gene (P < 0.001-0.016), and three-quarters of the treatment group had tumor index values that were indicative of near total tumor regression. Survival studies show that 50% of the ADV/RSV-tk treated mice are free of tumor at 160 days post adenovirus injection, while all controls died or required sacrifice within 43 days. These results demonstrate that clinically effective in vivo treatment of human squamous cell cancer can be achieved using adenovirus-mediated gene therapy. PMID- 7866993 TI - Differential effects of P-glycoprotein inhibitors on NIH3T3 cells transfected with wild-type (G185) or mutant (V185) multidrug transporters. AB - Multidrug resistance (MDR) may be associated with the expression of the MDR1 gene which encodes the 170-kDa cell surface P-glycoprotein (PGP) acting as an energy dependent multidrug efflux pump. This pump can be inhibited by a variety of drugs including cyclosporin A, quinidine, and verapamil. Substrate specificity of the MDR1 gene product can be altered by a point mutation at amino acid residue 185 in which valine is substituted for glycine, but the effect of this mutation on inhibition of PGP is unknown. Multidrug-resistant NIH3T3 cells transfected with the MDR1 retroviral vector pHaMDR-1/A (G185) or pHaMDR1/A (V185) expressing comparable levels of PGP were compared for patterns of drug resistance and inhibition of drug resistance by MDR reversing agents. The NIH-MDR-G185 transfectants were somewhat preferentially resistant to daunorubicin, taxol, and vinblastine. The mutant (V185) conferred increased resistance to colchicine. This MDR phenotype in both NIH-MDR-G185- and NIH-MDR-V185-transfected NIH3T3 cells was overcome by the addition of cyclosporin A, quinidine, or verapamil. Verapamil was the most potent of the three agents affecting wild-type PGP. However, specific inhibitors showed different potency with wild-type or mutant transporters, depending on the cytotoxic drug whose resistance was being reversed. For example, cyclosporin A at a concentration of 1 microgram/ml, was a powerful reverser of taxol and colchicine resistance for the mutant drug transporter, but was much less effective for the wild-type transporter. In contrast, verapamil reversed resistance to vinblastine more efficiently for the wild-type transporter than for the mutant transporter. These results suggest that the sensitivity of a multidrug transporter to a reversing agent will depend on the reversing agent, the cytotoxic drug, and the presence or absence of mutations which alter substrate specificity. PMID- 7866994 TI - Enhancement of 5-fluoro-2'-deoxyuridine antitumor efficacy by the uridine phosphorylase inhibitor 5-(benzyloxybenzyl)barbituric acid acyclonucleoside. AB - 5-(Benzyloxybenzyl)barbituric acid acyclonucleoside (BBBA) was recently synthesized as a potent and specific inhibitor of uridine phosphorylase (EC 2.4.2.3), the enzyme responsible for the catabolism of 5-fluoro-2'-deoxyuridine (FdUrd) in many types of tumors that are deficient or have little thymidine phosphorylase (EC 2.4.2.4) activity. The effect of BBBA on modulating the antitumor efficacy of FdUrd was evaluated in vitro, against the human colon carcinomas DLD-1 and HCT-15 grown in culture, and in vivo, against DLD-1 grown as xenografts in anti-thymocyte serum immunosuppressed mice. The concentrations of FdUrd that produced 50% growth inhibition after a 3-h exposure were 88 and 340 nM for HCT-15 and DLD-1, respectively. BBBA alone, at all concentrations tested, had no significant effect on the growth of DLD-1 and HCT-15 in culture. However, BBBA at 5, 10, 20, and 40 nM potentiated (P < 0.05) the cytotoxicity of FdUrd (340 nM; 3 h) against DLD-1 in culture by 20, 33, 55, and 63%, respectively. Similarly, BBBA at 10 and 20 nM potentiated the cytotoxicity of FdUrd (88 nM; 3 h) against HCT-15 in culture by 37 and 45%, respectively. In soft agar, BBBA (10 nM) also enhanced the cytocidal effect of FdUrd (10 and 32 nM) against DLD-1 by 41 and 55%, respectively, and against HCT-15 by 6 and 31%, respectively. Increasing BBBA dose to 20 nM enhanced further the FdUrd (10 and 32 nM) cytotoxicity against DLD 1 by 76 and 77%, respectively, and HCT-15 by 31 and 48%, respectively. BBBA also potentiated the chemotherapeutic efficacy of FdUrd in anti-thymocyte serum immunosuppressed mice bearing DLD-1 xenografts with no apparent host toxicity. At a low tumor burden (2.5 x 10(6) cells/mouse), 2 days treatment with FdUrd alone (50 mg/kg/day x 2) did not result in significant reduction in tumor volume. Coadministration of BBBA at 5 and 10 mg/kg/day x 2 did not potentiate the efficacy of FdUrd over that achieved by FdUrd alone, but it significantly reduced the tumor volume by 27 and 32%, respectively, when compared with untreated controls. FdUrd alone at 150 mg/kg/day x 2 reduced the tumor volume by 29%. This reduction in tumor volume was enhanced 1.8-fold by coadministration of BBBA (10 mg/kg/day x 2). At a higher tumor burden (5 x 10(6) cells/mouse) and 4 days treatment, BBBA at 10 and 30 mg/kg/day x 4 reduced further the tumor volume produced by FdUrd alone (200 mg/kg/day x 4) by 1.2- and 1.4-fold, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7866995 TI - Targeting of xenografted pancreatic cancer with a new monoclonal antibody, PAM4. AB - We have examined the ability of murine monoclonal antibody PAM4, directed against a pancreatic cancer-derived mucin, to target human pancreatic cancers carried as xenografts in athymic nude mice. Four tumor lines were used representing the range of expected differentiation; CaPan1, AsPc1, Hs766T, and BxPc3. In each case tumor uptake of PAM4 (range, 21-48% injected dose/g on day 3) was significantly higher than concomitantly administered, nonspecific, isotype-matched Ag8 antibody (range, 3.6-9.3% injected dose/g on day 3). Based upon the biodistribution data the estimated potential radiation dose delivered to the tumors when normalized to the blood dose as an estimate of dose-limiting myelotoxicity would be 13.1-, 2.2 , 3.4-, and 3.3-fold higher than to blood, respectively. PAM4 showed no evidence of targeting to normal tissues, except within the CaPan1 tumor model, where a small but consistent splenic uptake was observed. Splenic targeting was abolished by use of an increased PAM4 protein dose. Targeting of PAM4 to other normal tissues was not affected by the increased protein dose; however, tumor uptake of PAM4 (percentage of injected dose/g) was significantly increased by as much as 3 fold. The ability of PAM4 to target the CaPan1 tumor compared favorably to that of MN14, an anti-carcinoembryonic antigen murine monoclonal antibody. Tumor uptake of PAM4 was much greater than that for MN14 at days 1 and 3, whereas at later time points equivalent accumulations of activity were noted. Estimates of potential radiation doses to the tumor when normalized to the blood dose were 3.0 for MN14 and 9.6 for PAM4. These studies have shown that PAM4 is able to target pancreatic cancer with high specificity, achieving high concentrations at the tumor site. A rationale exists, then, for the performance of a clinical trial of radiolabeled PAM4 in the detection and localization of pancreatic cancer. PMID- 7866996 TI - Paternally derived H19 is differentially expressed in malignant and nonmalignant trophoblast. AB - The paternal allele of the H19 gene has been shown to be transcriptionally inactive in the developing human embryo. Using reverse transcription PCR and RNase protection assays, we demonstrate that expression of H19 is predominantly, but not exclusively, from the maternal allele in the human placenta. In situ hybridization analysis shows strong expression of the H19 gene in eight complete hydatidiform moles, hyperplastic tissues consisting of trophoblasts which contain only paternally derived genetic material, indicating that H19 is not functionally imprinted in this tissue. H19, a putative growth suppressor, is oppositely imprinted to the neighboring insulin-like growth factor II (IGF2) gene and an up regulation of IGF2 expression has been linked previously to a down-regulation of H19 expression in the progression to Wilms' tumor. Two cases of complete hydatidiform mole which progressed to choriocarcinoma show high levels of expression of both H19 and IGF2. The choriocarcinomas which developed from these complete hydatidiform moles showed similar expression of IGF2 but a decreased number of H19-positive cells, which may reflect selection for cells expressing IGF2 and against those expressing H19 in this tissue. PMID- 7866997 TI - Tyrosine phosphorylation is required for up-regulation of the HOX-11 (TCL-3) homeobox proto-oncogene in T cells. AB - HOX-11 (TCL-3) is a homeobox proto-oncogene isolated from the breakpoint region of the t(10;14) chromosomal translocation associated with pediatric T-cell acute leukemia. To better understand the transcriptional regulation of the HOX-11 gene in response to extracellular signals, the levels of HOX-11 RNA were examined in normal and leukemic human T cells upon phytohemagglutinin and hematopoietic growth factor stimulation. While individual hematopoietic growth factors tested did not show any effect on HOX-11 gene expression, a drastic increase in HOX-11 RNA was observed under the induction of phytohemagglutinin. In the presence of cycloheximide, a protein synthesis inhibitor, phytohemagglutinin-induced HOX-11 up-regulation was suppressed, indicating that HOX-11 acts as a delayed early response gene which requires protein synthesis. The HOX-11 gene expression was also suppressed by the tyrosine kinase inhibitors tryphostin and lavendustin A. Our data therefore suggest that the delayed early response of HOX-11 up regulation in T cells requires a tyrosine phosphorylation signal. PMID- 7866998 TI - An anoxia inducible endonuclease and enhanced DNA breakage as contributors to genomic instability in cancer. AB - Fischer rat embryo fibroblasts subjected to temporary anoxia followed by an aerobic recovery period show genomic instability in the form of highly elevated CAD gene amplification rates. As revealed by flow cytometric analysis this is associated with DNA breakage in vivo, followed by repair during the recovery period. Such genomic instability parallels expression of a M(r) 29,000/31,000 endonuclease; this enzyme requires no added divalent metal ion and has a pH optimum of about 6.5. The same endonuclease was found to be expressed within healing wounds and in four of ten human colorectal cancers but was not seen in eight normal colorectal tissue samples. Our results indicate that DNA breakage resulting from endogenous endonuclease activity can have a substantial effect in modulating genomic instability. PMID- 7866999 TI - Expression of the Met/hepatocyte growth factor receptor in human pancreatic cancer. AB - The c-MET oncogene encodes the receptor for hepatocyte growth factor (HGF) scatter factor, a multifunctional cytokine able to mediate morphogenesis as well as invasive growth of epithelial cells. The c-MET-encoded receptor is detectable only at low levels in the normal human exocrine pancreas, but it is up-regulated in the majority of pancreatic ductal adenocarcinomas. The c-MET-encoded HGF receptor is also overexpressed in a proportion of the panel of 31 human pancreatic cancer cell lines examined, which have a range of different growth properties and degrees of differentiation. In most cases the HGF receptor found in the malignant cells has features of the normal receptor. When added to pancreatic cancer cell lines, HGF triggers receptor phosphorylation and stimulates cells to move and proliferate. In overexpressing cell lines, the Met/HGF receptor is phosphorylated in the absence of endogenously produced or exogenously added ligand. These data suggest that the Met/HGF receptor may be involved in the growth and behavior of pancreatic cancer and may contribute to the ductal phenotype of these tumors. PMID- 7867000 TI - Retroviral insertional mutagenesis as a strategy for the identification of genes associated with cis-diamminedichloroplatinum(II) resistance. AB - Expression of resistance to cis-diamminedichloroplatinum(II) (CDDP), one of the most effective chemotherapeutic drugs used to treat a variety of malignancies, remains a serious obstacle for improving cancer treatment. To study possible genetic mechanisms underlying the development of CDDP resistance, we have adopted the approach of retroviral insertional mutagenesis. An early-stage CDDP-sensitive human melanoma cell line, WM35, was infected with a defective amphotropic murine retrovirus (murine stem cell virus), and the pooled cells were subsequently selected for CDDP-resistant variants. Nine CDDP-resistant clones independently derived from murine stem cell virus-infected WM35 cells were analyzed and it was found that five of these clones acquired an identical retroviral integration site, designated as CDDP resistance locus 1 (CRL-1), as revealed by isolation of retroviral flanking sequences. Furthermore, using the flanking sequence as probe, we have detected a 3.5-4.0-kilobase message, the expression of which is strongly increased in clones carrying a rearranged CRL-1 locus. These results strongly suggest that overexpression of CRL-1 confers resistance to CDDP in these clones. In addition, the present study indicates that retroviral insertional mutagenesis represents a potential strategy to identify genes responsible for CDDP resistance and possibly other chemotherapeutic drugs as well. PMID- 7867001 TI - Mice deficient in both p53 and Rb develop tumors primarily of endocrine origin. AB - To examine whether a cooperative role exists between inherited Rb and p53 deficiency in tumorigenesis, crosses were made between p53- and Rb-deficient mice and were monitored for subsequent tumor incidence and spectrum. Parental mice containing either Rb or p53 mutant alleles showed a predisposition for pituitary adenomas or lymphomas and sarcomas, respectively. Mice heterozygous for both Rb and p53 mutant alleles developed tumors of endocrine origin (medullary thyroid carcinomas, pancreatic islet cell carcinomas, and pituitary adenomas) in addition to lymphomas and sarcomas. Except for pituitary adenomas, these endocrine tumors were rarely seen in the parental p53 or Rb mutant mice. Mice deficient for both Rb and p53 showed a faster rate of tumor development than mice deficient only in Rb or p53. These results indicate that p53 and Rb do cooperate in the acceleration of tumorigenesis and in the development of endocrine tumor types. PMID- 7867002 TI - Protein metabolism in human colon carcinomas: in vivo investigations using a modified tracer technique with L-[1-13C]leucine. AB - To quantify the protein anabolism of tumors it is not sufficient simply to determine the level of protein synthesis. The decisive factor is the net balance. This is the first attempt to establish this parameter in human tumors in vivo. Intraoperative tumor leucine/protein metabolism was studied in 15 patients with resectable malignant colon tumors using a balance model and L[1-13C]leucine as the tracer substance. Comparative measurements were also carried out simultaneously for peripheral tissue (forearm); in addition, protein kinetics parameters were established for the whole body using a proven two-pool model (with the same tracer as above). In view of the frequently conflicting data on amino acid metabolism in tumors, the tumoral and peripheral exchange rates of 20 amino acids were also determined. In tumors, essential and branched-chain amino acid uptakes were found to be 1.68 +/- 0.59 (SE) and 1.52 +/- 0.23 mumol/100 g tissue/min, respectively; in peripheral tissue there was overall an amino acid release [-0.11 +/- 0.06 and -0.05 +/- 0.04 mumol/100 g/min; in either case P < 0.01 (tumor versus periphery)]. Tracer analyses yielded a net retention for the tumors but a protein loss for peripheral tissue (8.941 +/- 3.113 versus -0.557 +/ 0.53 g/kg/24 h; P < 0.01) and for the whole body (-0.363 +/- 0.04 g/kg/24 h). The tumors were divided into two prognostic groups on the basis of their histology. Significant differences were found between the two groups in terms of the net retention rate for 10 amino acids, including leucine; retention was elevated in tumors with an unfavorable prognosis, possibly due to a higher amino acid requirement because of more rapid growth or for export processes (mucus production). The protein balance model used here has proved satisfactory for our purposes and could also be used to directly evaluate dietary measures (e.g., adjuvant parenteral nutrition in connection with chemotherapy). PMID- 7867003 TI - Malignant transformation of the human endometrium is associated with overexpression of lactoferrin messenger RNA and protein. AB - In the mouse uterus, lactoferrin is a major estrogen-inducible uterine secretory protein, and its expression correlates directly with the period of peak epithelial cell proliferation. In this study, we examine the expression of lactoferrin mRNA and protein in human endometrium, endometrial hyperplasias, and adenocarcinomas using immunohistochemistry, Western immunoblotting, and Northern and in situ RNA hybridization techniques. Our results reveal that lactoferrin is expressed in normal cycling endometrium by a restricted number of glandular epithelial cells located deep in the zona basalis. Two thirds (8 of 12) of the endometrial adenocarcinomas examined overexpress lactoferrin. This tumor associated increase in lactoferrin expression includes an elevation in the mRNA and protein of individual cells and an increase in the number of cells expressing the protein. In comparison, only 1 of the 10 endometrial hyperplasia specimens examined demonstrates an increase in lactoferrin. We also observe distinct cytoplasmic and nuclear immunostaining patterns under different fixation conditions in both normal and malignant epithelial cells, similar to those previously reported in the mouse reproductive tract. Serial sections of malignant specimens show a good correlation between the localization of lactoferrin mRNA and protein in individual epithelial cells by in situ RNA hybridization and immunohistochemistry. Although the degree of lactoferrin expression in the adenocarcinomas did not correlate with the tumor stage, grade, or depth of invasion in these 12 patients, there was a striking inverse correlation between the presence of progesterone receptors and lactoferrin in all 8 lactoferrin positive adenocarcinomas. In summary, lactoferrin is expressed in a region of normal endometrium known as the zona basalis which is not shed with menstruation and is frequently overexpressed by progesterone receptor-negative cells in endometrial adenocarcinomas. PMID- 7867004 TI - Preclinical evaluation of LU 79553: a novel bis-naphthalimide with potent antitumor activity. AB - LU 79553 is a novel bis-naphthalimide which is highly cytotoxic in vitro with EC50 (concentration required for 50% inhibition of growth) ranging from 2 x 10( 7) to 5 x 10(-10) M. A number of studies were conducted to examine its antitumor activity in human xenograft models. In addition, we wanted to explore the possible schedule dependency of LU 79553 cytotoxicity in these xenograft models. Complete regression of MX-1 (mammary carcinoma) xenografts was observed when LU 79553 was administered i.v. daily for 5 doses at 20 mg/kg (2 cycles starting on Days 6 and 20) or every 3 days for 2 doses at 55 mg/kg (2 cycles starting on Days 6 and 13) or every 7 days for 4 doses. Complete regression was also seen in the MX-1 model when tumors were staged at 1-2 g prior to the initiation of treatment. Regressions (complete or partial) were observed in the LX-1 (lung), CX-1 (colon), DLD (colon), and LOX (melanoma) xenograft models. A significant increase in the median survival time of OVCAR-3- (ovarian carcinoma) bearing mice was noted in LU 79553-treated animals (treated/control = 195%). The excellent activity of this compound in such a wide variety of tumor types suggests LU 79553 merits further investigation in clinical trials. PMID- 7867005 TI - Nonrandom chromosomal change (trisomy 11) in murine plasmacytomas induced by an ABL-MYC retrovirus. AB - Trisomy of chromosome 11 (Ts11) is the second most frequent nonrandom chromosomal change in murine plasmacytomas (PCTs). The frequency of Ts11 is significantly higher in PCTs induced in pristane-conditioned mice infected by Abelson-murine leukemia virus (52%) compared to those induced by pristane alone (8.1%). Although the significance of Ts11 in mouse plasmacytomagenesis is not clearly understood it is hypothesized that a gene or genes located on chromosome (Chr) 11 may specifically promote the development of PCTs in which both oncogenes, c-myc and v abl, are abundantly expressed. To test this assumption we induced PCTs by three highly effective plasmacytomagenic retroviruses: ABL-MYC, J3V1, and RIM. Nearly 90% of PCTs that arose in BALB/c, (BALB/c x DBA/2N)F1, BALB/c-nu/nu, and 5-month old SCID mice infected with ABL-MYC virus were trisomic for Chr 11. In contrast, < 10% of PCTs induced by J3V1 or RIM retroviral constructs encompassing either v myc and v-raf or c-myc and v-Ha-ras oncogenes, respectively, contained Ts11. We have also investigated whether the entire Chr 11 or any particular subregion is preferentially duplicated in the process of ABL-MYC plasmacytomagenesis. By inducing PCTs in F1 heterozygous mice that are carriers of reciprocal translocations involving Chr 11 we found that the duplicated chromosomal region is located distal to the T4Dn breakpoint (11B5 band) on the telomeric segment of Chr 11. The regular duplication of this chromosomal segment strongly suggests the presence of a gene or genes whose amplification is of critical importance for v abl associated murine plasmacytomagenesis. PMID- 7867006 TI - Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck. AB - We evaluated the prognostic significance of overexpression of cyclin D1 in 47 patients with surgically resected squamous cell carcinomas of the head and neck. Overexpression of cyclin D1 was detected immunohistochemically using an affinity purified polyclonal antibody directed against the carboxyl-terminal part of the cyclin D1 protein, applied to formalin-fixed, paraffin-embedded tissue sections. Overexpression of cyclin D1 was found in 30 of 47 head and neck squamous cell carcinoma (HNSCC) cases and was associated with a more rapid and frequent recurrence of disease (P = 0.027). There was a 5-year disease-free interval of 47% for HNSCC patients with a strong overexpression of cyclin D1 and of 80% for cyclin D1-negative HNSCC patients. Overexpression of cyclin D1 was also associated with a shortened overall survival of these patients (P = 0.0095), with a 5-year survival of 60% for the cyclin D1 strongly positive cases and of 83% for cyclin D1-negative cases. Overexpression of cyclin D1 appears to indicate poor prognosis in operable HNSCC. PMID- 7867007 TI - Induction of apoptosis in liver tumors by the monoterpene perillyl alcohol. AB - The monoterpenes d-limonene and perillyl alcohol (POH) inhibit the growth of mammary tumors. In this investigation we tested whether POH is also effective in reducing liver tumor growth. Diethylnitrosamine was used to induce liver tumors in male Fischer 344 rats. Two weeks after diethylnitrosamine exposure was discontinued, the animals were divided into POH-treated and untreated groups. The mean liver tumor weight for the POH-treated rats after 19 weeks of POH treatment was 10-fold less than that for the untreated animals. POH did not influence tumor cell proliferation but increased the apoptotic index approximately 10-fold. The mRNA levels for the mannose 6-phosphate/insulin-like growth factor II receptor and the transforming growth factor beta type I, II, and III receptors were also significantly increased in the liver tumors from the POH-treated animals when compared to the corresponding receptor mRNA levels in the normal tissue surrounding the tumors and in the tumors of untreated animals. These results demonstrate that POH does not promote the formation of liver tumors, but rather inhibits their growth by enhancing tumor cell loss through apoptosis. PMID- 7867008 TI - Detection of CDKN2 deletions in tumor cell lines and primary glioma by interphase fluorescence in situ hybridization. AB - Deletions of chromosomal band 9p21 have been detected in various tumor types including melanoma, glioma, lung cancer, mesothelioma, and bladder cancer. Recently, the CDKN2 gene (p16INK4A, MTS I, CDK41) has been proposed as a candidate tumor suppressor gene because it is frequently deleted in cell lines derived from multiple tumor types. We performed fluorescence in situ hybridization (FISH) with interphase cells using yeast artificial chromosome clones and a cosmid contig of the CDKN2 region. In 10 cell lines (4 glioma, 2 melanoma, 2 non-small cell lung cancer, 2 bladder cancer) with 9p alterations detected by molecular or cytogenetic analysis, interphase FISH with the CDKN2 cosmid contig detected all 9p deletions previously identified by molecular analysis. Using this probe, FISH analysis of primary glioblastoma tumors revealed homozygous deletions of the CDKN2 region in 6 of 9 tumors (67%) whereas a yeast artificial chromosome probe containing the interferon type I (IFN) gene cluster was deleted in only 4 cases (44%). Thus, it is likely that the CDKN2 region is the target of 9p deletions in gliomas. Interphase FISH will play an important role in defining the clinical significance of 9p deletions in primary tumors because it is especially applicable to clinical samples which may be contaminated by normal cells. PMID- 7867009 TI - Early detection of Knudson's two-hits in preneoplastic renal cells of the Eker rat model by the laser microdissection procedure. AB - Hereditary renal cell carcinomas invariably develop by the age of 1 year in Eker rats. At the histological level, renal cell carcinomas develop through multiple stages from early preneoplastic lesions (e.g., phenotypically altered tubules) to adenomas. We previously reported that ionizing radiation induces additional tumors (large adenomas and carcinomas) in a linear dose-response relationship and that loss of heterozygosity (LOH) at chromosome 10, where the predisposing tuberous sclerosis (Tsc2) gene is localized, was found in the renal cell carcinomas which developed from hybrid F1 rats carrying the Eker mutation, indicating that in heterozygotes two events (one inherited, one somatic) are necessary to produce at least large adenomas and carcinomas. This study was designed to examine LOH in the earliest preneoplastic lesions, using a laser microdissection procedure. We could accurately dissect single altered renal tubules out of freeze-dried sections and clearly detected LOH in 4 of 19 altered tubules (21%). This is the first demonstration of LOH in single renal tubules. Our present results support the theory of a second, somatic mutation (second hit) as rate-limiting step of renal carcinogenesis in the Eker rat model of dominantly inherited cancer and the tumor suppressor nature of the Tsc2 gene function. PMID- 7867010 TI - Suppression of Bcl-2 messenger RNA production may mediate apoptosis after ionizing radiation, tumor necrosis factor alpha, and ceramide. AB - Recent studies have proposed that tumor necrosis factor alpha (TNF-alpha) and ionizing radiation induce apoptosis by activating hydrolysis of sphingomyelin to ceramide. Bcl-2 and a related gene, Bcl-X, inhibit several forms of apoptosis. Herein, we report that internucleosomal DNA fragmentation, characteristic of apoptosis and induced by ionizing radiation, is accompanied by concomitant decreases in Bcl-2 and Bcl-X mRNA levels in HL-60 and U-937 human leukemia cells. Apoptotic DNA fragmentation after exposure to TNF-alpha and C2-ceramide was also associated with down-regulation of Bcl-2 mRNA in HL-60 and U-937 cells, while Bcl X mRNA production was unaffected. These results suggest that modulation of Bcl-2 gene expression may be a target for ceramide-mediated apoptosis following exposure to ionizing radiation and TNF-alpha. Changes in Bcl-2 expression may be the basis for the interactive killing observed between radiation and TNF-alpha in some human and tumor cells. PMID- 7867011 TI - Induction of apoptosis at different oxygen tensions: evidence that oxygen radicals do not mediate apoptotic signaling. AB - Apoptosis has been hypothesized to be mediated through the induction of free radicals via oxidative pathways. Furthermore, it has been proposed that Bcl-2 acts to inhibit apoptosis induced by a wide variety of stimuli by preventing the production of oxygen-derived free radicals. Since the generation of oxygen free radicals is dependent upon oxygen concentration, this hypothesis would lead to the prediction that the concentration of oxygen should affect the induction of apoptosis. In order to test this prediction, we have examined the induction of apoptosis in T-lymphoma cell lines S49.1 and WEHI 7.1 by dexamethasone and by withdrawal of serum from myc-immortalized fibroblasts in 95% oxygen, atmospheric oxygen (20%), and hypoxic conditions of up to 125-fold less oxygen. Culture in 95% oxygen induced apoptosis in all cells tested, confirming that oxidative damage can lead to apoptosis. However, for one cell line, WEHI 7.1, hypoxia also induced apoptosis. Furthermore, for the other cell lines tested, induction of apoptosis by either dexamethasone or by serum withdrawal was not affected by hypoxia. These results are not consistent with the hypothesis that apoptosis is mediated via oxygen-generated free radical formation. PMID- 7867012 TI - Human gliomas with wild-type p53 express bcl-2. AB - Human astrocytomas frequently overexpress wild-type p53, which suggests that gliomas have evolved a mechanism to subvert p53-mediated apoptosis. bcl-2 inhibits apoptosis mediated by p53, and it is expressed in several human cancers. We therefore examined a series of human gliomas to determine whether bcl-2 is expressed and whether this expression is associated with tumors which have wild type p53. Twenty-eight paraffin-embedded gliomas (3 WHO grade II, 13 grade III, 12 grade IV) were immunohistochemically stained for bcl-2 and p53. p53 mutations were identified with single strand conformation polymorphism and DNA sequencing. Sixteen of 28 (57%) tumors expressed bcl-2, and bcl-2 expression was associated with wild-type p53 (P < 0.01). Among gliomas which overexpressed p53, bcl-2 was positive in 7 of 7 tumors with wild-type p53 but in only 1 of 7 with mutant p53 (P < 0.01). We conclude that bcl-2 is frequently expressed in human gliomas and that expression is more common in tumors with wild-type p53. PMID- 7867013 TI - Comparative effects of milk, yogurt, butter, and margarine on mammary tumorigenesis induced by 7,12-dimethylbenz(a)anthracene in rats. AB - The effects of margarine and butter on mammary tumorigenesis were compared in the first experiment. Altering the levels of dietary margarine and butter influenced the development of mammary tumors induced with 7,12-dimethylbenz(a)anthracene (DMBA) in rats. Margarine enhanced tumorigenesis dose dependently in both the incidence and the number of mammary tumors. On the other hand, butter that was substituted for margarine did not show any enhancing effects. Inasmuch as butter is made from cow's milk, the effect of cow's milk was studied in the second experiment. It was expected that milk might inhibit mammary tumorigenesis. Contrary to our expectations, however, milk and yogurt did not inhibit but enhanced the DMBA-induced mammary tumorigenesis. It remains to be elucidated whether the enhancing effect was caused by some specific factors in milk or by the difference in energy or nutrient intakes. PMID- 7867014 TI - Women and lung cancer: a comparison of active and passive smokers with nonexposed nonsmokers. AB - Prior to the 1920s, lung cancer was a rare disease. However, the current increase in lung cancer appears to parallel the increase in smoking for both men and women with a 30- to 50-year delay. National lung cancer deaths continue to rise, with over 168,000 total deaths estimated in 1992. Women are now showing higher percentage increases in lung cancer than men from active smoking. The data from the Erie County Study on Smoking and Health (ECSSH), a population study, were used to measure the effects of both active and passive smoking on women's lung cancer mortality. The three major categories of exposure (no known or minimal exposure, passive smoking exposed, and active smoking) were used in the analyses. The results from the population data in Erie County, PA, were based on 528 nonexposed nonsmoking women, 3138 exposed nonsmoking women, and 1747 smoking women. Deaths due to lung cancer as a percentage of total deaths excluding traumatic deaths were 0.2% for the nonexposed nonsmoking women, 0.9% for the exposed nonsmoking women, and 8.0% for women who smoked. The data showed that women smokers died of lung cancer at a rate 9 times greater than exposed nonsmokers and 42 times greater than nonexposed nonsmokers. PMID- 7867015 TI - Do neuroendocrine cells, particularly the D-cell, play a role in the development of gastric stump cancer? AB - Previously, we have shown that a significant proportion of human gastric carcinomas of the diffuse type may be neuroendocrine tumors derived from the enterochromaffinlike (ECL) cell. The growth of the ECL cell is specifically regulated by gastrin, suggesting an important role of gastrin in human gastric carcinogenesis. However, patients with antral-resected stomachs have reduced plasma gastrin and despite that an increased risk of gastric cancer. Recently, it has been shown that gastrin has a negative trophic effect on the oxyntic D-cell of the rat. The present study evaluates whether gastric stump carcinomas are D cell derived. Twenty gastric stump carcinomas that had developed from 20 to 53 years after antral resection were examined for neuroendocrine differentiation by neuron-specific enolase immunohistochemistry and for D-cell origin by somatostatin immunohistochemistry. Half the tumors were classified as gastric carcinomas of the intestinal type, while the other half initially was classified as gastric carcinomas of the diffuse type. One of these latter tumors could, however, be reclassified as carcinoid tumor by appearance in hematoxylin erythrosin saffron-stained sections as well as by neuron-specific enolase positivity. Interestingly, this tumor was also positive for somatostatin, suggesting D-cell origin. Three other tumors were positive for neuron-specific enolase, but they were negative for somatostatin. Nevertheless, this study suggests that some gastric stump carcinomas may be malignant neuroendocrine tumors derived from neuroendocrine cells and possibly from D-cells. Furthermore, this study may indicate an important role for hormones and neuroendocrine cells in human gastric carcinogenesis. PMID- 7867016 TI - A clinicopathological analysis of early gastric cancer: retrospective study with special reference to lymph node metastasis. AB - We reviewed 217 cases of early gastric cancer (EGC) resected from 1978 through 1988. To determine the indications for curative resection by endoscopic mucosectomy (EM) for EGC, we paid special attention to lymph node metastasis examined after gastrectomy. The overall incidence of lymph node metastasis was 12.4%. It was 3.4% for mucosal (m-) cancer and 23.5% for submucosal (sm-) cancer. The maximum diameter of the lesion, depth of cancerous invasion, and location of the lesion showed positive correlations with lymph node involvement (p < 0.05). EGCs less than 20 mm in diameter had no lymph node metastasis. Pieces of mucosa about 20 mm in diameter on the average could be obtained with a single EM procedure. EGC with ulceration had a higher incidence of lymph node involvement than did that without ulceration. We conclude that if EM reveals an intramucosal gastric carcinoma less than 20 mm in diameter without ulceration, curative resection by EM is indicated. PMID- 7867017 TI - The expression of HLA class I antigen in prostate cancer in relation to tumor differentiation and patient survival. AB - The expression of HLA class I antigens was studied using the immunoperoxidase technique on 30 patients with prostate cancer and 29 patients with benign prostatic hypertrophy (BPH). Forty-three percent of the tumors stained positive, in contrast to 21% of the BPH. An inverse relationship was noted between class I expression and degree of tumor differentiation: 88% of the well-differentiated tumors (8/9) expressed class I antigen, compared with 33% (3/9) of the moderately differentiated and 16% (2/12) of the poorly differentiated tumors. No significant survival difference was found between those with class I-positive and -negative tumors. However, when both class I expression and degree of differentiation were considered, those with positive tumors at each level of differentiation had better survival than those with negative tumors. These data suggest that HLA class I expression may serve as a finite prognostic factor and may have relevance in future immunotherapy. PMID- 7867018 TI - Use of screening mammography by general internists. AB - While physician endorsement has been shown to be highly important in motivating women to obtain screening mammograms, there is evidence that doctors do not refer women for the procedure as often as they should. The objective of this study was to help understand why physicians do not routinely utilize screening mammography. Randomly selected Washington State general internists were surveyed by mail, concerning mammography, during 1989. An expanded theory of reasoned action was used as a broad conceptual framework for considering factors potentially associated with use. The survey response rate was 66%, yielding a study sample of 85. Only 38% of the respondents reported they always ordered mammograms for women aged 50 years and over during preventive office visits. Nearly half (43%) had no reminder system for the test. Correlates of use included beliefs concerning the screening behavior of other doctors, the location of mammography facilities in relation to physician offices, and age. Physician-related barriers, such as doubts about effectiveness, were found to affect use more than patient-related barriers, such as cost. The recommendations of professional organizations were shown to have been important in influencing physician use of screening mammography. This study indicates a proportion of general internists are not routinely ordering mammograms for their age-eligible female patients. The findings identify barriers to use of mammography that need to be overcome if national efforts to promote use of the procedure by primary care physicians are to succeed. Implications for intervention are reviewed. PMID- 7867019 TI - Cervical mass screening in Norway--510,000 smears a year. AB - In 1990 the Norwegian Department of Health and Social Affairs decided to start a national screening program for cervical cancer. All women aged 25 to 70 years are offered cervical screening every 3 years. The mass screening is organized and run by a central unit, comprising the Cancer Registry of Norway and the National Health Screening Service. For the first 3 years, all spontaneous cervical screening in Norway is recorded in a central, computerized register. In addition, a pilot project has been implemented in two counties to evaluate the organizational aspects of the screening program. A total of 509,641 cervical smears were recorded during the first year of registration. The test frequency was highest in the age group 20 to 29 years (28.4%), while relatively few tests were performed on women in the age group 60 to 69 years (6.6%). The majority of smears (88.6%) had normal tissue morphology, whereas 2.9% displayed different cytological abnormalities. Human papillomavirus (HPV) changes and mild (CIN 1) and moderate (CIN 2) dysplasia had the highest smear rate in women under 40 years. Malignant cellular changes had the highest rate in older age groups. The imbalance in the age distribution of smears and the confinement of cytological abnormalities to the youngest and the oldest age groups support the wide target age range of the screening program. PMID- 7867020 TI - Fluorimetric studies of calmodulin interactions with antiestrogens. AB - Recent cumulative data have shown that tamoxifen and its metabolites inhibit the activation of cAMP phosphodiesterase by calmodulin (CaM). In this study, the interaction of antiestrogens with CaM was investigated using a hydrophobic fluorescent probe, 2-p-toluidinylnaphthalene-6-sulfonate (TNS). Tamoxifen (TAM) enhanced the fluorescence of TNS bound to CaM and shifted the emission maximum to lower wavelengths. These effects were concentration-dependent. No change in the apparent affinity of TNS for CaM was noted in the presence of TAM. These results suggest that TAM bound to CaM at sites distinct from those of TNS and induced a change in TNS environment. Interaction of TAM metabolites with CaM depended on the degree of alteration of the dimethylaminoethoxy side-chain. Thus, N desmethylation or N-di-desmethylation notably reduced the interaction of the drug with the macromolecule by 24 and 77% respectively. Side-chain deamination to the primary alcohol (metabolite Y) totally suppressed the interaction. The ability of these different metabolites to interact with CaM correlates with their efficiency to inhibit CaM-dependent cAMP phosphodiesterase and their growth inhibitory potency reported previously. PMID- 7867021 TI - Tamoxifen and ZK 119010 exert mixed agonistic and antagonistic effects on pS2 expression in MCF-7 cells. AB - pS2 is a major estradiol-inducible gene in MCF-7 breast cancer cells. In this study we tested the effects of tamoxifen and ZK 119010, a novel nonsteroidal antiestrogen, on pS2 gene expression with or without a pretreatment of cells with estradiol (10(-11), 10(-8) M). Estradiol increased pS2 expression in MCF-7 cells approximately 12-fold. Tamoxifen (10(-6) M) reduced estradiol-induced pS2 expression to 78% of the stimulated level, while ZK 119010 was 50% effective. Given alone, either of the two antiestrogens in the above concentrations evoked a pS2 gene expression in MCF-7 cells significantly above background levels. From these data we conclude that the antiestrogens tamoxifen and ZK 119010 possess both antagonistic and agonistic potencies in MCF-7 cells. However, the antiestrogenic potency of ZK 119010 seems to be higher than that of tamoxifen. PMID- 7867022 TI - A novel gene-transfer technique mediated by HVJ (Sendai virus), nuclear protein, and liposomes. AB - There have been many reports of in vivo direct gene transfer methods, but there are problems with these methods. Recently, we developed a novel, nontoxic and efficient in vivo direct gene transfer method mediated by Sendai virus (HVJ) and liposomes. In our system, foreign genes and nuclear proteins were encapsulated into the same liposomes, which were then treated with inactivated HVJ. The properties of our system are that HVJ enables foreign genes to be introduced directly into the cytoplasm by membrane fusion and that nuclear proteins transport the foreign genes rapidly into the nuclei. In the present study, we succeeded in introducing and expressing the functional gene for human insulin, and we observed the expression of this gene in mouse plasma and the reduction of plasma glucose. Our system will provide a new method of gene transfer aimed at postnatal gene therapy in various diseases. PMID- 7867023 TI - The role of radiotherapy in the treatment of breast cancer: results of perioperative implantation. AB - Between 1982 and 1993, 620 of 938 patients with pathologically staged I-II breast cancer were treated at the time of reexcision (perioperatively), with an iridium 192 (Ir-192) implant to the tumor bed to give 2000 cGy to the 30 to 40 cGy/ph isodose line. This was followed by 4500 cGy to the entire breast at 180 cGy/d for 25 fractions. The local control for the 620 patients at 5 and 10 years was 93 and 89%, respectively. The actuarial survival at 5 and 10 years was 92 and 81%. The cosmetic results were good to excellent for 87% of the patients. Chemotherapy had no impact on local control in this study. Ir-192 implant is especially useful for deep tumors, making possible more flexibility in the techniques used to boost the tumor volume. Perioperative implantation has increased the accuracy of placing the boost dose, shortened the overall treatment time, and, for some patients, eliminated the need for rehospitalization and anesthesia. PMID- 7867024 TI - Myocardial ischaemia: can we agree on a definition for the 21st century? PMID- 7867025 TI - Immune effector mechanisms in heart transplant rejection. PMID- 7867026 TI - Attachment procedures for mechanical manipulation of isolated cardiac myocytes: a challenge. PMID- 7867027 TI - Sydney Ringer viewed in a new light. PMID- 7867029 TI - Long term bradycardia by electrical pacing: a new method for studying heart rate reduction. AB - OBJECTIVE: The aim was to develop a method of inducing bradycardia on a chronic basis by electrical pacing and to study its effect upon myocardial capillarity in pigs. METHODS: Farm pigs were instrumented with Medtronic dual chamber telemetric pacemakers and two leads, either both atrial or one atrial and one ventricular. Bradycardia was achieved by linking pacing stimuli to endogenous atrial or ventricular events for the different electrode positions respectively, and monitored postoperatively for 4-5 weeks by implanted telemetric ECG devices. Myocardial capillary supply (lectin staining) and myocyte cross sectional areas were then estimated in sections of the left ventricle. RESULTS: Heart rates were reduced by 40-50 beats.min-1 at operation from a resting rate of 110(SEM 3) beats.min-1 in eight animals and bradycardia maintained upon recovery from anaesthesia for up to five weeks, with no obvious limitations for the animals. After this time, heart rates measured under anaesthesia were found to remain low for up to 2 h after pacing had been switched off. There was no evidence of myocyte hypertrophy, yet mean capillary density.mm-2 was significantly increased by pacing, from 1470(50) to 1734(82), p < 0.02. CONCLUSIONS: It is possible to produce primary heart rate reduction in the pig by a novel means of pacing on a chronic basis, leading to increased myocardial capillary supply without myocyte hypertrophy. This method can provide a basis for future investigations of the beneficial effects of heart rate reduction in the vascularly compromised heart. PMID- 7867028 TI - Vagal release of vasoactive intestinal peptide can promote vagotonic tachycardia in the isolated innervated rat heart. AB - OBJECTIVE: The aim was to determine the extent to which endogenous release of vasoactive intestinal polypeptide (VIP) might be implicated in the modulation of sinoatrial rate in the presence and absence of muscarinic blockade or beta blockade. METHODS: Langendorff perfused rat hearts were studied with the right vagus intact. The hearts were maintained in sinus rhythm and subjected to right vagal stimuli of 5, 10, 20, and 30 Hz. RESULTS: Administration of exogenous VIP, 10(-8) M, increased sinus rate by 20% (p < 0.05). This increase in heart rate was reduced significantly to 8% by the VIP antagonist [D-p-Cl-Phe6, Leu17]VIP, 10(-7) M, which alone had no effect on sinus rate. Vagal stimulation reduced sinus rate from a control of 254(SEM 2) to 164(17) beats.min-1 (p < 0.05) at 20 Hz. VIP, 10( 8) M, increased these rates to 284(6) and 220(21) beats.min-1 (p < 0.05). In another eight vagally stimulated hearts, frequencies of 5-20 Hz reduced sinus rate. At 30 Hz heart rate increased in five, and the resultant rate was significantly faster in these [154(10) beats.min-1] than in the remainder [98(12) beats.min-1, p < 0.05]. Vagal stimulation also increased sinus rate (p < 0.05) in four of seven additional hearts perfused with atropine, 2 x 10(-6) M. This increase was completely abolished by [D-p-Cl-Phe6, Leu17]VIP. That the effect was not beta adrenergic was demonstrated in eight experiments using atropine plus propranolol, 1 x 10(-7) M. A vagally induced increment in rate still occurred (p < 0.05) and was abolished by [D-p-CL-Phe6, Leu17]VIP. The ability to ascribe a rate change to VIP release was maximal in the presence of propranolol and atropine, intermediate in the presence of atropine alone, and minimal in the absence of muscarinic or beta blockade. CONCLUSIONS: Vagally released VIP is capable of limiting the decrement in sinus rate that occurs at high frequencies of vagal stimulation, and in some circumstances can actually increment sinus rate. Its role as an endogenous modulator of vagal effects on heart rate and as a possible cause of vagal and postvagal tachycardias should be further explored. PMID- 7867030 TI - Effect of an ATP sensitive potassium channel opener, levcromakalim, on coronary arterial microvessels in the beating canine heart. AB - OBJECTIVE: The aim was to clarify the site in the coronary microcirculation that is dilated by an ATP sensitive potassium channel opener, levcromakalim, and to examine whether the magnitude of dilatation is size dependent. METHODS: Coronary arterial microvessels were observed through an intravital microscope equipped with a floating objective in beating canine left ventricles in situ. Flow velocity of the left anterior descending coronary artery was measured with a suction-type Doppler probe. Heart rate and aortic pressure were maintained at control levels throughout the experiments. Three doses of levcromakalim (0.01-1.0 microgram.kg-1.min-1) or a single dose (1.0 microgram.kg-1.min-1) were infused into the coronary artery in groups, with or without intracoronary glibenclamide pretreatment (200 or 400 micrograms.kg-1). The effect of levcromakalim on different sized vessels was assessed by dividing them into three groups according to control diameter (small, internal diameter < 100 microns; medium, > or = 100, < 200 microns; large, > or = 200 microns). RESULTS: The lowest dose of levcromakalim dilated only the small vessels. The two higher doses dilated vessels of all sizes, but the magnitude of dilatation was greater in the small vessel group than in the other two groups. Coronary resistance significantly decreased dose dependently during the infusion of 0.1 and 1.0 microgram.kg-1.min 1 of levcromakalim. Pretreatment with glibenclamide markedly attenuated the levcromakalim induced dilatation of all vessel groups and the reduction in coronary vascular resistance. CONCLUSIONS: Levcromakalim heterogeneously dilates coronary arterial microvessels via the opening of ATP sensitive potassium channels, and small vessels are more sensitive to levcromakalim. PMID- 7867031 TI - Effects of sympathetic stimulation, with and without previous alpha 1 and beta adrenoceptor blockade, on refractoriness dispersion in canine heart. AB - OBJECTIVE: The aim was to determine the electrophysiological effects of cardiac sympathetic stimulation, with and without prior alpha 1 and beta adrenoceptor blockade during myocardial ischaemia in dogs. METHODS: Chloralose anaesthetised dogs were studied 2 h after ligation of the obtuse marginal branches of the circumflex artery (OMB). The refractory period was measured at eight sites in the ischaemic zone, two sites in the border zone, and two sites in the normal zone with S1-S2 extrastimulus methods. RESULTS: In group 1 (n = 13), before OMB ligation, stimulation of the ventrolateral cardiac nerve shortened the refractory period only in the ischaemic zone (p < 0.01). OMB ligation resulted in a significant shortening of the refractory period in the ischaemic zone (p < 0.01). In group 2 (n = 12), the alpha 1 blocker bunazosin (0.2 mg.kg-1, intravenously) blunted the shortening of the refractory period in the ischaemic zone induced by OMB ligation (p < 0.01), resulting in a reduction in refractory period dispersion between the ischaemic and non-ischaemic (border and normal) zones. Subsequent administration of the beta blocker propranolol (0.2 mg.kg-1, intravenously) prolonged refractory periods both in the ischaemic and in the non-ischaemic zones (p < 0.05 v p < 0.001). Ventrolateral cardiac nerve stimulation reversed the effects of bunazosin on the refractory period in the ischaemic zone; however, after the addition of propranolol, neural stimulation no longer influenced the refractory period. In group 3 (n = 13), propranolol (0.2 mg.kg-1, intravenously) reversed the shortening of the refractory period in the ischaemic zone (p < 0.01) induced by OMB ligation but also prolonged the refractory period in the non ischaemic zone (p < 0.001); refractory period dispersion between the ischaemic and non-ischaemic zones was thus not reduced. Ventrolateral cardiac nerve stimulation had no effect on refractory period after administration of propranolol alone or propranolol followed by bunazosin. CONCLUSIONS: Although an alpha 1 blocker may be better than a beta blocker in reducing refractory period dispersion between the ischaemic and non-ischaemic myocardium, a beta blocker may protect more effectively than an alpha 1 blocker against the detrimental effects of cardiac nerve activity on electrical instability in the ischaemic myocardium. PMID- 7867032 TI - Simulated ischaemia and reperfusion in isolated guinea pig ventricular myocytes. AB - OBJECTIVE: The objectives were (1) to develop a cellular model of simulated ischaemia and reperfusion in isolated ventricular myocytes; (2) to determine effects of simulated ischaemia and reperfusion on calcium current (ICa), transient inward current (ITI) and contraction; and (3) to determine whether pharmacological agents which alter intracellular sodium and calcium loading affect signs of calcium overload in reperfusion in this model. METHODS: Electrical activity was recorded with conventional and voltage clamp techniques. Cell shortening was measured with a video edge detector. Myocytes were equilibrated in Tyrode solution, exposed to simulated ischaemia (hypoxia, acidosis, lactate, hyperkalaemia, glucose-free) for 20 min, and reperfused with Tyrode solution. RESULTS: Ischaemia depolarised myocytes [-89(SEM 1) to -67(4) mV, p < 0.05], abbreviated action potential duration [APD90, 257(14) to 188(12) ms, p < 0.05], and abolished contractions. Contractions elicited by voltage clamp steps also were abolished in ischaemia; however, ICa decreased by only 51% [ 0.98(0.08) to -0.50(0.06) nA, p < 0.05]. Signs of calcium overload, including aftercontractions, oscillatory afterpotentials, and ITI, occurred in 69% of myocytes in reperfusion. Upon reperfusion, both APD90 and ICa recovered slowly; however, contractions returned quickly and temporarily exceeded control. Amiloride during ischaemia and reperfusion lowered incidence of ITI in reperfusion, whereas nifedipine and lignocaine had no effect on ITI. CONCLUSIONS: This model of ischaemia and reperfusion in ventricular myocytes shows many features of multicellular preparations, such as membrane depolarisation and action potential duration shortening during ischaemia, and appearance of oscillatory afterpotentials upon reperfusion. Inhibition of contraction during ischaemia and recovery of contraction in reperfusion are independent of changes in APD90 or ICa. Induction of aftercontractions, oscillatory afterpotentials, and ITI in reperfusion is associated with reduced peak ICa. Amiloride most probably decreased signs of calcium overload in early reperfusion by inhibiting sodium loading via Na+/H+ exchange. Additionally, amiloride may inhibit ITI directly by blocking Na+/Ca2+ exchange. PMID- 7867033 TI - Dilating effect of perivascularly applied potassium channel openers cromakalim and pinacidil in rat and cat pial arteries in situ. AB - OBJECTIVE: The aim was to test the vasodilator effect of perivascularly applied potassium channel openers cromakalim and pinacidil in pial arteries of cat and rat. METHODS: Using an open cranial window technique the diameter of pial arteries in the parietal cortex of rat and cat was recorded with an image splitting method. Employing micropuncture techniques, test compounds were dissolved in inert cerebrospinal fluid and infused into the perivascular space of individual arteries. RESULTS: Cromakalim (7 x 10(-18)-7 x 10(-13) M) induced concentration dependent dilatation of feline pial arteries with a maximum effect of 26.8(SEM 3.2)% at 7 x 10(-15) M. In rat arteries, cromakalim had a maximum effect of 32.1(4.97)% at 10(-15) M, while pinacidil (10(-10)-10(7) M) exerted a maximum dilatation of 29.5(3.3)% at 10(-8) M. The latter is consistent with previous findings in feline pial arteries. The sulphonylurea glibenclamide (10( 8)-10(-6) M) had no effect on the resting diameter of rat and cat pial arteries, indicating that their resting tone is not influenced by mechanisms involving ATP sensitive potassium channels. However, glibenclamide reduced the dilating effect of cromakalim and pinacidil in rat and cat in a dose dependent manner. CONCLUSIONS: A comparison with previously published data obtained in isolated middle cerebral and basilar arteries showed that potassium channel openers of the benzopyrane and cyanoguanidine type are much more potent in pial arteries than in peripheral arteries in situ or in isolated arteries of the circle of Willis and of peripheral vascular beds. PMID- 7867034 TI - Enhanced leucocyte adhesion to interleukin-1 beta stimulated vascular smooth muscle cells is mainly through intercellular adhesion molecule-1. AB - OBJECTIVE: The aim was to investigate whether interleukin-1 beta (IL-1 beta) plays a role in modulating the adhesion of monocytes and neutrophils to vascular smooth muscle cells, and to identify what molecules on these cells may be involved in the adhesion. METHODS: Rat aortic smooth muscle cells were challenged with IL-1 beta and tested for adhesion of prelabelled monocytes and neutrophils. Northern analysis, reverse transcription/polymerase chain reaction (RT/PCR), and immunocytochemical staining were used to measure the changes of intercellular adhesion molecule-1 (ICAM-1) and other adhesion molecules in response to IL-1 beta stimulation. Neutralising antibody against ICAM-1 was used to demonstrate a role of ICAM-1 in this IL-1 beta induced adhesion. RESULTS: IL-1 beta induced the adhesion of monocytes and neutrophils to aortic smooth muscle cells in a concentration and time dependent manner. IL-1 beta-induced adhesion was inhibited by preincubation of the cells with an IL-1 receptor antagonist (IL-1ra). Northern analysis and RT/PCR showed that ICAM-1 mRNA represents a predominant adhesion molecule induced by IL-1 beta, and that the expression of ICAM-1 mRNA precedes and parallels the induced adhesion profiles of aortic smooth muscle cells for leucocytes. Immunocytochemical staining confirmed the IL-1 beta induced ICAM-1 expression on the smooth muscle cells. Moreover, a monoclonal anti-rat ICAM-1 antibody produced a concentration dependent inhibition of the IL-1 beta induced adhesion of monocytes and neutrophils to the smooth muscle cells. CONCLUSIONS: IL 1 beta actively regulates functional ICAM-1 expression in vascular smooth muscle cells. The IL-1 beta-induced expression of ICAM-1 on the smooth muscle cells may be an important contributor to the increased adhesion by monocytes and neutrophils to these cells and suggests that IL-1 beta might play a role in the proinflammatory and immune functions of the modified smooth muscle cells during atherosclerosis and restenosis. PMID- 7867035 TI - Filling of a model left ventricle studied by colour M mode Doppler. AB - OBJECTIVE: It has been proposed that the early diastolic flow pattern inside the left ventricle reflects ventricular diastolic function. The flow pattern often divides into two phases towards the apex. The aim of this study was to examine the hydrodynamic nature of this phenomenon. METHODS: A rubber balloon representing the ventricle was connected to a reservoir representing the atrium, both filled with anticoagulated blood. Rigid "mitral" orifices 20 mm long and 15 40 mm in diameter were used. Surrounding the ventricle was a water filled chamber to which suction could be applied. The colour M mode Doppler sample beam coincided with the ventricular long axis. Colour M mode measures velocity at multiple sites along the beam simultaneously. The timing and magnitude of the velocities were analysed digitally. The filling was also qualitatively studied by ultrasonic two dimensional sector scanning. RESULTS: At the start of the filling, blood moved simultaneously at all levels, behaving as a fluid column. This was denoted "phase I". A flow wave then propagated from the mitral orifice towards the apex, called "phase II". This was found to represent a ring vortex, with blood velocities twice its propagation velocity [ratio 2.1(SEM 0.016)]. The ratio between the velocity time integrals of phase II and phase I decreased progressively from 51(15) to 0.41(0.14) when mitral orifice diameter was increased in 5 mm steps from 15 mm to 40 mm (p < 0.001). The propagation velocity correlated strongly with peak transmitral blood velocity, r = 0.95, p < 0.001. The flow patterns resembled patterns recorded in patients. CONCLUSIONS: The two phases of the filling pattern represented the motion of a blood column and the propagation of a ring vortex, respectively. Mitral orifice size determined which phase dominated the flow pattern. PMID- 7867036 TI - Phosphatidic acid increases in response to noradrenaline and endothelin-1 in adult rabbit ventricular myocytes. AB - OBJECTIVE: The aim was to assess whether noradrenaline and endothelin-1 can stimulate endogenous production of phosphatidic acid in adult ventricular myocytes. METHODS: After stimulation of rabbit ventricular myocytes with noradrenaline and endothelin-1, total lipids were extracted using the Bligh and Dyer procedure and separated by thin layer chromatography, and phosphatidic acid was quantified using photodensitometric analysis of visualised lipids with CuSO4/H3PO4. RESULTS: Noradrenaline (10(-5) M) elicited a rapid increase in phosphatidic acid at 2 min, followed by a decrease at 5 min. A second delayed and sustained increase in phosphatidic acid occurred at 10 min. The response to noradrenaline (10(-9) to 10(-5) M) was concentration dependent with a half maximum response (EC50) of 3.1 x 10(-8) M and the maximum effect at 10(-6) M. The increase in phosphatidic acid production in response to noradrenaline was abolished by an alpha 1 adrenergic receptor blocking agent (2-[beta-(4 hydroxyphenyl)-ethylaminomethyl]tetralone) but unaffected by the beta adrenergic blocking agent L-propranolol. An increase in phosphatidic acid was also elicited in rabbit ventricular myocytes in response to endothelin-1. The response was time and concentration dependent with the maximal increase at 12 min, EC50 5.3 x 10( 9) M, and maximum effect at 10(-6) M. Both noradrenalin and endothelin-1 stimulated phosphatidylbutanol production in the presence of butanol (100 mM), indicating that both agonists activate phospholipase D. CONCLUSIONS: Noradrenaline at physiological concentrations elicits both a rapid and a delayed increase in phosphatidic acid in adult rabbit ventricular myocytes. Endothelial 1, at physiological concentrations, also stimulates an increase in the mass of phosphatidic acid in myocytes, but the increase induced by endothelin-1 is monophasic, in contrast to the biphasic response seen during stimulation with noradrenaline. Activation of phospholipase D contributes to the increase in phosphatidic acid seen during stimulation of myocytes with either noradrenaline or endothelin-1. These are the first data to characterise endogenous production of phosphatidic acid in isolated adult ventricular myocytes. PMID- 7867037 TI - Transforming growth factor beta 1 and extracellular matrix gene expression in isoprenaline induced cardiac hypertrophy: effects of inhibition of the renin angiotensin system. AB - OBJECTIVE: The aim was to investigate changes in cardiac transforming growth factor beta 1 (TGF-beta 1), fibronectin, and collagen types I and III mRNA levels in isoprenaline induced cardiac hypertrophy, and the effects of delapril, an angiotensin converting enzyme inhibitor, and TCV-116, an angiotensin II type 1 receptor antagonist, on this hypertrophy. METHODS: Rats were continuously infused with saline and low or high dose of isoprenaline (0.5 or 3 mg.kg-1.d-1) by an osmotic minipump for 24 h, 48 h or 7 d. Treatment with delapril (100 mg.kg-1.d-1) or TCV-116 (10 mg.kg-1.d-1) was started from 1 d before the implantation of minipump to the end of experiments. After the experimental periods, left ventricular weight was measured and the mRNA was extracted and measured by northern blot hybridisation. RESULTS: Both low and high doses of isoprenaline infusion resulted in increased left ventricular weight. With low dose infusion, cardiac TGF-beta 1 mRNA was not stimulated throughout the infusion, while fibronectin mRNA and collagen types I and III mRNAs began to increase at 24 h and 48 h, respectively, after the infusion. In high dose isoprenaline infusion, not only was extracellular matrix mRNA but also TGF-beta 1 mRNA in the ventricle significantly increased. TCV-116 prevented isoprenaline induced left ventricular hypertrophy as much as delapril. However, with delapril or TCV-116, the time course of TGF-beta 1 and ECM mRNA expression was almost similar to isoprenaline infusion only. CONCLUSIONS: The extracellular matrix mRNA expressions are enhanced in myocardial hypertrophy by a low dose of isoprenaline, which is probably not mediated by TGF-beta 1. The preventive effects of TCV-116 on this hypertrophy indicate that the inhibitory effects of angiotensin converting enzyme inhibitor on cardiac hypertrophy are due to the inhibition of angiotensin II and that angiotensin II type I receptor plays an important role in isoprenaline induced left ventricular hypertrophy. However, the renin-angiotensin system may play a minor role in isoprenaline induced cardiac fibrosis. PMID- 7867038 TI - Non-neurogenic contractions in isolated coronary arteries by brief electrical pulses. AB - OBJECTIVE: The aim was to describe a novel form of non-neurogenic coronary artery contraction. METHODS: Superfused cattle coronary artery preparations in vitro were placed between platinum electrodes and stimulated. RESULTS: The preparations responded to exceedingly brief transmural stimulation (a single ten thousandth of a second pulse) with long lasting [150(SEM 18.5) s] contractions. These previously undescribed contractions were not reduced by neural blockade nor did they involve free radicals, prostaglandins, or the endothelium. In contrast to the rapid loss of responses to KCl in zero calcium Krebs solution, responses to stimulation were only progressively diminished over many minutes, suggesting involvement of internal calcium stores. The L channel calcium antagonists nifedipine and diltiazem markedly reduced contractions to KCl but did not materially alter those to 1, 5, or 10 stimulation pulses, nor did the T channel antagonist tetramethrin, further supporting the involvement of stored calcium in contractions to stimulation. Evidence was obtained that neither Na+/K(+)-ATPase nor the Na+/Ca+ exchanger are involved in the contractions to stimulation. Ryanodine in zero calcium Krebs solution potentiated contractions to stimulation with 10 pulses and also to endothelin, but depressed contractions to U 46619. CONCLUSIONS: Stimulation at excitation parameters well below those associated with neurotransmitter release activates a highly effective contraction sequence that may use a ryanodine insensitive pool of bound calcium. This novel process may have physiological and pathophysiological relevance and provides a means of activating contraction in a coronary artery and studying its time course and contributory components, without the complicating participation of an agonist drug. PMID- 7867039 TI - Sodium pump current measured in cardiac ventricular myocytes isolated from control and potassium depleted rabbits. AB - OBJECTIVE: The aim was to investigate cardiac muscle sodium pump function following chronic potassium depletion in rabbits. METHODS: Sodium pump current was measured using the whole cell voltage clamp technique in ventricular myocytes from control rabbits or rabbits with chronic dietary potassium depletion, under conditions designed to minimise all other electrogenic channels, pumps, and exchangers. The effects of changes in external [K+] and intracellular [Na+] were investigated. Experiments were performed on ventricular myocytes enzymatically isolated from adult rabbits, average weight 2.5 kg, which were fed either a control (n = 6), or a potassium deficient diet (n = 8) for 25 d. RESULTS: Potassium depletion significantly increased the sodium pump current density recorded with 10 mM extracellular [K+] and 50 mM [Na+] in the pipette (conditions which activate an estimated 98% of the maximally available pump current), from 1.53(SEM 0.05) pA.pF-1 (control, n = 4) to 1.740(0.06) pA.pF-1 (potassium depleted, n = 4; p < 0.05). The relationship between sodium pump current and extracellular [K+] (30 mM [Na+] in pipette) showed a significant leftward shift in myocytes from potassium depleted animals, such that the Km was reduced from 1.270(0.10) (control, n = 4) to 0.72(0.11) mM (potassium depleted, n = 4; p < 0.05). The effect of varying pipette [Na+] on sodium pump current was examined in cells superfused with 5 mM [K+]. The Km was again reduced from 19.44 mM (control) to 16.91 mM (potassium depleted). The Hill coefficients for activation of the pump by potassium and sodium were essentially unchanged, as was the shape of the current-voltage relationship. CONCLUSIONS: These results suggest that chronic potassium depletion results in an adaptation of the cardiac sodium pump such that pump activity can be maintained, or even enhanced, despite a fall in plasma [K+]. This adaptation is achieved by both alterations in ionic sensitivity to potassium and sodium, and an increase in maximum activity. The latter may reflect an increase in sodium pump site density. These changes are likely to account for the preservation of intracellular [K+] in cardiac muscle during chronic potassium deficiency. PMID- 7867040 TI - Aldosterone and cardiac fibrosis: in vitro studies. AB - OBJECTIVE: Increased cardiac collagen is seen in uninephrectomised rats made hypertensive by aldosterone infusion and high salt, with the possibility of a direct effect of aldosterone at the level of the cardiac fibroblast. The aim of this study was to examine the effects of aldosterone, glucocorticoids, and angiotensin II on collagen production in a series of rat cardiac fibroblast cultures. METHODS: Cardiac fibroblast cultures were established from neonatal and adult rats of Sprague-Dawley, WKY, and SHR strains, with collagen synthesis measured by incorporation of [3H]proline into collagen. Cells were grown alone or co-cultured with cardiomyocytes, and exposed to aldosterone, glucocorticoids, or angiotensin II for 24-28 h before determination of [3H]proline incorporation. RESULTS: Aldosterone did not affect production of collagen; in contrast, angiotensin II increased, and the glucocorticoid agonist RU28362 suppressed, collagen production in cultured cardiac fibroblasts in the various rat strains. CONCLUSIONS: Aldosterone does not exert a direct effect on collagen synthesis in rat cardiac fibroblasts grown in culture. The increased cardiac collagen observed in vivo in aldosterone treated, salt loaded rats may thus represent secondary effects of aldosterone in this model. PMID- 7867041 TI - Free radical related myocardial mitochondrial damage following limb ischaemia reperfusion. AB - OBJECTIVE: The aim was to define the following: (1) if reperfusion of ischaemic limbs could cause myocardial damage; (2) if reactive oxygen metabolites are involved in such possible damage. METHODS: Ten rats underwent ischaemia reperfusion of the lower limbs (group A) and 10 underwent the same procedure following treatment with ascorbic acid (group B). Ten rats were used as a control group (group C). RESULTS: The incidence of severe myocardial mitochondrial damage and serum malondialdehyde concentrations 30 min after reperfusion were both higher in group A than in groups B and C [8/10, 2/10, and 0/10, p < 0.05 and 7.25 (SEM 0.33), 5.30(0.26), and 4.89(0.23) mumol.litre-1, p < 0.05, respectively]. CONCLUSIONS: Ischaemia-reperfusion of the lower limbs may cause mitochondrial damage in the myocardium and reactive oxygen metabolites could mediate this damage. PMID- 7867042 TI - Could the "real" preconditioning mechanism please stand up? (or, a polyplanic platitude to preconditioning) PMID- 7867043 TI - Forearm blood flow response to NO synthase inhibitor in essential hypertension. PMID- 7867044 TI - Effect of air-drying on demineralized and on sound coronal human dentine: a study on density and on lesion shrinkage. AB - Recently, several papers investigated the linear dimensional changes in dentine after air-drying. This paper pertains to weight changes, volume changes, and density changes caused by air-drying of sound and demineralized intact dentine. The densities of sound and artificially demineralized human coronal dentine were measured in the wet state and after various drying periods of up to 24 h. The volume was assessed either by means of a pyknometer (wet samples) or by means of dimension measurements. The air-drying experiments were done using a Mettler thermobalance at room temperature. The density of wet sound coronal dentine was found to be 2.24 +/- 0.12 g.cm-3; the value of wet demineralized dentine was about 1.6 g.cm-3. The data show that previously published density values of powdered sound dentine may have been influenced by powdering effects, air-drying, and air inclusion. In whole demineralized air-dried dentine, air inclusion can be very severe: up to 30% by volume. The results show furthermore that in demineralized dentine we have two drying stages: during the first one (up to about 10 min of air-drying), the lesions shrink about 23%, while a main part of the water in the lesion evaporates, and air is incorporated into the tissue; during the second stage (drying longer than 10 min), the lesions hardly shrink anymore, but water is evaporated mainly from underlying sound dentine, followed by air incorporation. PMID- 7867045 TI - A new method for in vivo quantification of changes in initial enamel caries with laser fluorescence. AB - A new method for the in vivo assessment of changes in initial enamel caries lesions was developed and tested. A CCD camera equipped with a high-pass filter (lambda > 520 nm) collects the fluorescence image of carious teeth, illuminated intraorally with diffuse laser light (lambda = 488 nm). Incipient lesions show a loss in fluorescence to be expressed as a percentage of fluorescence radiance of sound tissue. A PC program (Inspektor, model QLF 1.0) is used for display, storage, and subsequent analysis of images. To enable the calculation of fluorescence loss, the fluorescence of sound tissue at the lesion site is reconstructed from the radiances of sound tissue bordering the lesion. This method was tested on 19 visually sound buccal surfaces in vivo. The differences between actual and reconstructed radiance was -1.6 +/- (SD) 1.1%, over areas varying between 8 and 14 mm2. The repeatability of the caries quantification was tested by measuring one arrested initial caries lesion 25 times in vivo. The lesion area was 0.56 +/- 0.20 mm2, and the loss of fluorescence was 17.6 +/- 0.7%, corresponding to a lesion depth of 17 +/- 2 microns. The new quantitative method was applied for the testing of an in vivo caries model using plaque accumulating brackets on premolars scheduled for extraction. Videoimages were recorded in vivo before bracketing and 0, 2, 3, and 5 weeks after debracketing. Clear changes between the different time points were recorded for both lesion size and mineral content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867047 TI - Urinary fluoride excretion in children with low fluoride intake or consuming fluoridated salt. AB - The purpose of this study was to compare urinary fluoride excretion with fluoride ingestion in children who had either a low fluoride intake or received supplemental fluoride through salt or water. The urinary samples were collected in two ways. In procedure A, urine was collected in the morning, at noon and during the afternoon. This covered a continuous period of approximately 7 h from the beginning to the end of the school day. In procedure B, morning, afternoon and night samples were collected. The morning and afternoon samples were obtained under supervision at school. Procedure B was more useful than procedure A for monitoring salt fluoridation projects. Children with a history of low fluoride intake excreted a mean of 10 micrograms F/h during the night and the morning, but 13-16 micrograms F/h after the main meal. Children in a water-fluoridated town or in comprehensive salt fluoridation programs excreted between 19 and 33 micrograms F/h. However, after the intake of meals prepared with fluoridated salt (250 ppm F) the mean excretion of fluoride ranged between 31 and 49 micrograms F/h. The levels of excretion corresponded with the levels of fluoride intake and meal patterns in the various groups. PMID- 7867046 TI - Fluorosis-like effects of acidosis, but not NH+4, on rat incisor enamel. AB - Previous studies have shown that chronic acidosis induced by NH4Cl is associated with disturbances in enamel mineralization that resemble severe fluorosis and increased fluoride concentrations in both soft and hard tissues. It has not been shown whether these effects are due to acidosis per se or exposure to high levels of NH+4. This 42-day study with rats fed a low-fluoride diet was done to identify the etiological factor. Two control groups received deionized water or water containing NaCl. Two groups received NH+4-containing compounds that did not produce acidosis (NH4HCO3 or HN4 acetate). Two other groups were rendered acidotic by exposure to NH4Cl in the drinking water (metabolic acidosis) or to an atmosphere containing 10% CO2 (respiratory acidosis). The femur epiphysial fluoride concentrations were elevated in the NH4Cl and NH4 acetate groups, and the magnesium concentrations were elevated in the groups exposed to NH+4 compounds and in the 10% CO2 group. Microradiographic analysis revealed severe disturbances in the mineralization pattern of incisor enamel in both acidotic groups, but normal enamel in the other groups. Enamel fluoride and magnesium concentrations were highest in the acidotic groups. The enamel fluoride concentrations were low (8-14 ppm) and not regarded as the cause of the defective mineralization. It was concluded that the effects on structure and composition of enamel were due to acidosis and not to exposure to high levels of NH+4. PMID- 7867048 TI - Urinary fluoride excretion in Jamaica in relation to fluoridated salt. AB - The purpose of this study was to compare the urinary fluoride levels in subtropical Jamaica just before the beginning of salt fluoridation (250 mg/kg salt) in 1987 and again 20 months later. Four age groups were studied in three locations with low to intermediate fluoride concentrations in the drinking water. The averages of supervised, timed morning fluoride excretions ranged between 12.1 and 27.9 micrograms/h prior to fluoridation as compared with 23.7-67.4 micrograms/h 20 months after the beginning of the sale of fluoridated salt. The fluoride excretions obtained from 24-hour collections ranged from 169 to 485 micrograms/24 h in 1987 and increased to 304-657 micrograms/24 h in 1989. In 1987, the morning fluoride excretions approximated those of French and Swiss children who had a low fluoride intake, but the fluoride levels of 1989 were similar to the data obtained from children who had an intake of 1.2-1.7 mg F/day or consumed fluoridated water. PMID- 7867049 TI - Cariogenic bacteria in a longitudinal study of approximal caries. AB - Two hundred and seventeen approximal spaces, initially caries free, in 58 patients were studied clinically and radiographically, at intervals of 6 months, for 3 years. Samples of approximal dental plaque were removed for culture of Streptococcus mutans, Streptococcus sobrinus, and lactobacilli. During the study approximal caries developed in 16 subjects (27.6%) at 30 sites (13.8%), involving 42 teeth. 56 of 58 (96.7%) subjects harboured S. mutans at some time during the study, 62.1% lactobacilli, and 29.3% had S. sobrinus. The counts of S. mutans were significantly higher in those subjects that also carried S. sobrinus than in the remaining subjects. A persisting high count of S. mutans > 10(5) colony forming units per millilitre (CFU/ml) or a count that rose by > or = 1 x log10 CFU/ml during the study was seen in 25 of 30 sites that subsequently became carious (p < 0.001). Similarly, counts of lactobacilli that were consistently > 10(3) CFU/ml or rising by > or = 1 x log10 CFU/ml were seen in 17 of 30 sites that became carious (p < 0.001). Although there were strong statistical associations between approximal caries and high or rising counts of these cariogenic bacteria, the bacterial counts were not good predictors of future approximal caries at that particular site. PMID- 7867050 TI - A comparison of the microbial flora in carious dentine of clinically detectable and undetectable occlusal lesions. AB - It is not known whether the aetiology of occlusal hidden caries lesions (HCL) is identical to that of small visible lesions (SVL). Previous studies of the microflora of HCL suggest that relatively few species can be isolated. The aim of the present study was to compare the bacterial composition of dentine from 10 HCL and 17 SVL in a population of children aged 8-18 years. The following bacteria were identified: Actinomyces spp., mutans streptococci, Streptococcus sanguis, Streptococcus oralis, Streptococcus gordonii. Streptococcus mitis, and Lactobacillus spp. Streptococcus mutans was found more often in the HCL group (p = 0.03), while Streptococcus sobrinus was found more often in the SVL group (p = 0.05). However, proportions of both species were lower in the SVL group as compared with the HCL group (S. mutans p = 0.07; S. sobrinus p = 0.03). Lactobacilli and Actinomyces spp. were found at similar levels in both groups. A more diverse range of streptococcal species and Veillonella was found in the SVL group (p = 0.001). These results show a less complex microflora in HCL as compared with SVL, indicating that the aetiology of hidden caries might be different from that of open caries. PMID- 7867051 TI - Fluoride concentration, mutans streptococci and lactobacilli in plaque from old glass ionomer fillings. AB - Previous studies have found that the fluoride concentration of plaque growing on or adjacent to glass ionomer cement (GIC) is increased and the proportion of mutans streptococci in plaque is reduced. So far, there are only a few studies of the long-term effect of glass ionomer fillings on plaque in vivo. The aim of this study was to determine whether old GIC fillings have effects on plaque fluoride and microflora and whether this effect can be increased by topical application of fluoride on GIC fillings in vivo. The participants were 27 adults with at least 3 GIC fillings about 3 years old. Plaque was collected from sites adjacent to the GIC fillings and from the contralateral teeth, after which a 1.2% fluoride gel was applied to all teeth. Three days later, plaque was collected from the same sites as before. Stimulated saliva was also collected at both appointments. The results show that none of the patients had elevated levels of fluoride in their saliva either before or 3 days after the fluoride treatment. The fluoride concentration was 0.51 microgram/mg protein in plaque on GICs and 0.35 microgram/mg protein in plaque on contralateral teeth (p = 0.028). After the fluoride treatment, the respective fluoride concentrations were 0.59 microgram/mg and 0.75 microgram/mg (p = 0.849). No significant differences in the proportion of mutans streptococci and lactobacilli in plaque from GIC and contralateral teeth were found. The results suggest that the fluoride concentration of plaque growing on old GIC fillings is slightly increased. In this study, however, this had no significant effect on the cariogenic microflora.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867052 TI - Effects of sugar restriction on Streptococcus mutans and Streptococcus sobrinus in saliva and dental plaque. AB - The effect of sugar restriction on the oral levels of mutans streptococci was studied in 20 subjects fulfilling three criteria: (1) having more than 300,000 CFU mutans streptococci/ml saliva, (2) harbouring both Streptococcus mutans and Streptococcus sobrinus in saliva, and (3) eating sugar frequently. The subjects were randomly divided into a test group (n = 12), who were asked to refrain from using sugar-containing foods between meals and to reduce sugar in main meals for 6 weeks, and a control group (n = 8), who did not receive any dietary advice. Saliva and plaque samples were collected at baseline and at 3, 6 and 12 weeks. The results showed that the levels of S. mutans and S. sobrinus decreased in saliva and plaque during the 6-week sugar restriction period. The decrese in mutans streptococci was more pronounced on buccal than on approximal tooth surfaces. Both species seemed to react in a similar way to the sugar restriction in saliva as well as in dental plaque. At the follow-up examination at 12 weeks, i.e. 6 weeks after completing the sugar restriction period, the numbers of S. mutans and S. sobrinus had increased again, but were still lower when compared to the baseline values. PMID- 7867053 TI - Comparison of the efficacy of 40% chlorhexidine varnish and 1% chlorhexidine fluoride gel in decreasing the level of salivary mutans streptococci. AB - The aim of the study was to compare the efficacy of a 40% chlorhexidine (CHX) varnish (EC40, Certichem, Nijmegen, The Netherlands) with a 1% CHX-0.2% NaF gel in decreasing the level of salivary mutans streptococci (MS). The subjects were screened for a high level of MS using a Dentocult-SM strip method (Orion Diagnostica, Finland). In varnish groups with fluoride (VCHXF, n = 20) and without fluoride (VCHX, n = 19), the CHX varnish was applied on dry teeth using an ampoule and an anesthetic syringe with blunt needle, and removed after 15 min. In group VCHXF an additional 2.26% fluoride varnish (Duraphat, Woelm Pharma GmbH, Eschwege, Germany) was applied. The CHX-NaF gel treatment included the application of the gel with rubber cups and dental tape for 5 min on three occasions during a week in group GCHXF (n = 21). The level of MS (MSB agar) was significantly lower after 4 weeks than at baseline in VCHX (p < 0.001) and VCHXF (p < 0.05), but not after 12 weeks. In GCHXF a significant decrease (p = 0.001) was observed after 4 weeks only with the strip method. In VCHX and VCHXF the strip values for MS were still reduced after 12 weeks. In VCHX and GCHXF a small, although statistically significant, increase was observed in the total number of microorganisms after 4 and 12 weeks. Opinions on taste sensations associated with the treatments were generally negative, but least negative in the VCHXF group; fewer side effects were also reported in the VCHXF group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867055 TI - Effect of addition of 0.103% citrate to a blackcurrant drink on plaque pH in vivo. AB - The aim of the present study was to investigate whether the addition of a small amount of citrate to infant fruit drinks resulted in a similar beneficial effect to that reported recently with 10% sucrose solution. A popular blackcurrant drink was tested with and without added 0.103% citrate by measuring its ability to depress plaque pH in 20 adult subjects using the plaque-harvesting technique. Solutions of 10% sucrose and 10% sorbitol were used as positive and negative controls, respectively. The results showed that the blackcurrant drink with added citrate had a significantly weaker plaque pH response as compared with the blackcurrant drink without added citrate and 10% sucrose (positive control). The mean areas enclosed by the pH curve below pH 6.0 (+/- SD) were 10% sorbitol (negative control) 0.00, blackcurrant with 0.103% citrate 1.85 +/- 1.07, plain blackcurrant 4.65 +/- 2.11, and 10% sucrose 6.25 +/- 2.35. The acidogenic potential of the blackcurrant drink with added citrate was less than half as compared with the plain blackcurrant drink. It was concluded that the addition of relatively low levels of citrate to a blackcurrant drink reduces the acidogenic response in plaque. PMID- 7867054 TI - Potential cariogenicity of starches and fruits as assessed by the plaque-sampling method and an intraoral cariogenicity test. AB - The cariogenicity of starches and fruits was investigated by measuring acidogenicity (plaque sampling) and enamel demineralization. Test foods were oranges, apples, bananas, Cornflakes, Branflakes, Weetabix, Alpen (no added sugar), white bread, wholemeal bread, rice, and spaghetti, with positive and negative controls of sucrose and sorbitol. Plaque sampling indicated that all the foods were less acidogenic than sucrose, but only significantly so (p < 0.05), as follows: maximum drop in plaque pH: all foods; minimum plaque pH reached: Cornflakes, Branflakes, and wholemeal bread; cH area: wholemeal bread. All foods produced enamel demineralization. The low pH of oranges and apples caused more demineralization than sucrose. Overall, the foods were less cariogenic than sucrose, but more than sorbitol. PMID- 7867056 TI - Propagation of light through human dental enamel and dentine. AB - Techniques based on transillumination of teeth with visible light will be a valuable aid in caries diagnosis, if a higher sensitivity than that of the present Foti method is achieved. Therefore, a better understanding of light propagation through teeth is required, and hence it is useful to investigate the propagation of light through sound dental material. In this study the intensities emanating from the surfaces of enamel and dentine bars were measured when these bars were illuminated using a fibre rod transporting the light from a HeNe laser (lambda = 633 nm) as a light source. From the measured intensities, the radiant fluxes emanating from the surfaces were calculated. To account for a directional dependence of these fluxes, optical anisotropy in dental material was investigated by comparing the transmitted light intensity in a direction perpendicular and parallel to the approximal surface of the tooth from which the sample was cut. The mean ratio of the transmitted intensities in perpendicular and parallel direction was 0.86 +/- 0.06 for enamel and 2.88 +/- 0.43 for dentine. In addition, for enamel the asymmetry parameter, g, was estimated. The averaged value was g = 0.68 +/- 0.09. It was concluded that for dentine the optical anisotropy as measured supports the idea that tubules are the predominant cause of scattering in dentine. For enamel the results indicate that the hydroxyapatite crystals contribute significantly to scattering and that the influence of the prism structure on the light propagation is small. PMID- 7867057 TI - Hedgehog and beyond. PMID- 7867058 TI - Replication arrest. PMID- 7867059 TI - The bacterial flagellum: from genetic network to complex architecture. PMID- 7867060 TI - NF-kappa B: a lesson in family values. PMID- 7867061 TI - Multiple Ras functions can contribute to mammalian cell transformation. AB - We have developed a generalized approach, using two hybrid interactions, to isolate Ha-Ras effector loop mutations that separate the ability of Ha-Ras to interact with different downstream effectors. These mutations attenuate or eliminate Ha-ras(G12V) transformation of mammalian cells, but retain complementary activity, as demonstrated by synergistic induction of foci of growth-transformed cells, and by the ability to activate different downstream components. The transformation defect of Ha-ras(G12V, E37G) is rescued by a mutant, raf1, that restores interaction. These results indicate that multiple cellular components, including Raf1, are activated by Ha-Ras and contribute to Ha Ras-induced mammalian cell transformation. PMID- 7867062 TI - cAMP-dependent protein kinase and hedgehog act antagonistically in regulating decapentaplegic transcription in Drosophila imaginal discs. AB - Localized expression of decapentaplegic (dpp) is required for proper development of the Drosophila imaginal discs. Using genetic mosaics, we show that in the anterior compartment of appendage discs and anterior to the morphogenetic furrow in the eye disc, cells that lack cAMP-dependent protein kinase (PKA) activity ectopically express dpp. Pka- cells can influence the fate of neighboring cells to reorganize anterior patterns in appendages and trigger ectopic morphogenetic furrows in the developing retina. This organizing activity of Pka mutant cells depends on dpp activity. Our findings suggest that PKA is a component of a signaling pathway that represses dpp expression and that hh antagonizes this pathway to maintain dpp expression at the anterior-posterior compartment border and in the morphogenetic furrow. PMID- 7867063 TI - Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development. AB - Reduced protein kinase A (PKA) activity in anterior imaginal disc cells leads to cell-autonomous induction of decapentaplegic (dpp), wingless (wg), and patched (ptc) transcription that is independent of hedgehog (hh) gene activity. The resulting nonautonomous adult wing and leg pattern duplications are largely due to induced dpp and wg expression and resemble phenotypes elicited by ectopic hh expression. Inhibition of PKA in anterior cells close to the posterior compartment can substitute for hh activity to promote growth of imaginal discs, whereas overexpression of PKA can counteract transcriptional induction of ptc by hh in these cells. PKA therefore appears to be an integral component of the mechanism by which hh regulates the expression of key patterning molecules in imaginal discs. PMID- 7867064 TI - Protein kinase A and hedgehog signaling in Drosophila limb development. AB - The Drosophila hedgehog (hh) gene encodes a secreted protein involved in organizing growth and patterning in many developmental processes. Hh appears to act by inducing the localized expression of at least two other signaling molecules, decapentaplegic (dpp) and wingless (wg), which then govern cell proliferation and patterning in surrounding tissue. Here, we demonstrate that cyclic AMP (cAMP)-dependent protein kinase A (PKA) is essential during limb development to prevent inappropriate dpp and wg expression. We also show that a constitutively active form of PKA can prevent inappropriate dpp and wg expression, but does not interfere with their normal induction by hh. We propose that the basal activity of PKA imposes a block on the transcription of dpp and wg and that hh exerts its organizing influence by alleviating this block. PMID- 7867065 TI - I kappa B-beta regulates the persistent response in a biphasic activation of NF kappa B. AB - We have cloned the cDNA encoding I kappa B-beta, one of the two major I kappa B isoforms in mammalian cells. The recombinant I kappa B- beta protein interacts with equal affinity to p65 and c-Rel and does not exhibit a preference between these Rel proteins. Instead the primary difference between I kapp B-alpha and I kappa B-beta is in their response to different inducers of NF-kappa B activity. One class of inducers causes rapid but transient activation of NF-kappa B by primarily affecting I kappa B-alpha complexes, whereas another class of inducers causes persistent activation of NF-kapa B by affecting both I kappa B-alpha and I kappa B-beta complexes. Therefore, the overall activation of NF-kappa B consists of two overlapping phases, a transient phase mediated through I kappa B-alpha and a persistent phase mediated through I kappa B-beta. PMID- 7867066 TI - Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast. AB - The silent mating loci and chromosomal regions adjacent to telomeres of S. cerevisiae have features similar to heterochromatin of more complex eukaryotes. Transcriptional repression at these sites depends on the silent information regulators SIR3 and SIR4 as well as histones H3 and H4. We show here that the SIR3 and SIR4 proteins interact with specific silencing domains of the H3 and H4 N-termini in vitro. Certain mutations in these factors, which affect their silencing functions in vivo, also disrupt their interactions in vitro. Immunofluorescence studies with antibodies against RAP1 and SIR3 demonstrate that the H3 and H4 N-termini are required for the association of SIR3 with telomeric chromatin and the perinuclear positioning of yeast telomeres. Based on these interactions, we propose a model for heterochromatin-mediated transcriptional silencing in yeast, which may serve as a paradigm for other eukaryotic organisms as well. PMID- 7867067 TI - Cloning of a novel bacteria-binding receptor structurally related to scavenger receptors and expressed in a subset of macrophages. AB - A novel murine plasma membrane protein has been identified in subpopulations of macrophages. It has an intracellular N-terminal domain, a transmembrane domain, and an extracellular region with a short spacer, an 89 Gly-Xaa-Yaa repeat containing collagenous domain, and a C-terminal cysteine-rich domain. In situ hybridization and immunohistochemical staining have localized the protein to a subset of macrophages in the marginal zone of the spleen and the medullary cord of lymph nodes. No expression was observed in macrophages of liver or lung. Transfected COS cells synthesized a native trimeric plasma membrane protein that bound labeled bacteria and acetylated LDL, but not yeast or Ficoll. The results suggest that the novel protein is a macrophage-specific membrane receptor with a role in host defense, as it shows postnatal expression in macrophages, which are considered responsible for the binding of bacterial antigens and phagocytosis. PMID- 7867068 TI - Ectopic expression of the flagellar regulon alters development of the Bordetella host interaction. AB - Signal transduction molecules within the two-component family represent a conserved adaptation for the control of genes involved in pathogenesis. The Bordetella virulence control locus, bvgAS, activates and represses gene expression in response to environmental signals. While infection requires virulence gene activation, the role of gene repression during infection is not understood. By altering regulatory genes and reversing regulatory connections, we found evidence that the BvgAS-repressed genes responsible for motility are neither required nor expressed during colonization of the host. Expression of this Bvg- phase-specific phenotype in the Bvg+ growth phase resulted in a defect in tracheal colonization. Therefore, BvgAS promotes virulence both by activating genes required for colonization and by repressing genes that inhibit the development of infection. PMID- 7867069 TI - Nucleocapsid and glycoprotein organization in an enveloped virus. AB - Alphaviruses are a group of icosahedral, positive-strand RNA, enveloped viruses. The membrane bilayer, which surrounds the approximately 400 A diameter nucleocapsid, is penetrated by 80 spikes arranged in a T = 4 lattice. Each spike is a trimer of heterodimers consisting of glycoproteins E1 and E2. Cryoelectron microscopy and image reconstruction of Ross River virus showed that the T = 4 quaternary structure of the nucleocapsid consists of pentamer and hexamer clusters of the capsid protein, but not dimers, as have been observed in several crystallographic studies. The E1-E2 heterodimers form one-to-one associations with the nucleocapsid monomers across the lipid bilayer. Knowledge of the atomic structure of the capsid protein and our reconstruction allows us to identify capsid-protein residues that interact with the RNA, the glycoproteins, and adjacent capsid-proteins. PMID- 7867070 TI - Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18). AB - We have determined the high resolution crystal structure of the A domain from the alpha chain of integrin CR3. The domain adopts a classic alpha/beta "Rossmann" fold and contains an unusual Mg2+ coordination site at its surface. One of the coordinating ligands is the glutamate side chain from another A domain molecule. We suggest that this site represents a general metal ion-dependent adhesion site (MIDAS) for binding protein ligands. We further propose that the beta subunits of integrins contain a MIDAS motif within a modified A domain. Our crystal structure will allow reliable models to be built for other members of the A domain superfamily and should facilitate development of novel adhesion modulatory drugs. PMID- 7867071 TI - Crystal structure of a paired domain-DNA complex at 2.5 A resolution reveals structural basis for Pax developmental mutations. AB - The 2.5 A resolution structure of a cocrystal containing the paired domain from the Drosophila paired (prd) protein and a 15 bp site shows structurally independent N-terminal and C-terminal subdomains. Each of these domains contains a helical region resembling the homeodomain and the Hin recombinase. The N terminal domain makes extensive DNA contacts, using a novel beta turn motif that binds in the minor groove and a helix-turn-helix unit with a docking arrangement surprisingly similar to that of the lambda repressor. The C-terminal domain is not essential for prd binding and does not contact the optimized site. All known developmental missense mutations in the paired box of mammalian Pax genes map to the N-terminal subdomain, and most of them are found at the protein-DNA interface. PMID- 7867072 TI - Crystal structure of the replication terminator protein from B. subtilis at 2.6 A. AB - The crystal structure of the replication terminator protein (RTP) of B. subtilis has been determined at 2.6 A resolution. As previously suggested by both biochemical and biophysical studies, the molecule exists as a symmetric dimer and is in the alpha + beta protein-folding class. The protein has several uncommon features, including an antiparallel coiled-coil, which serves as the dimerization domain, and both an alpha-helix and a beta-ribbon suitably positioned to interact with the major and minor grooves of B-DNA. A site has been identified on the surface of RTP that is biochemically and positionally suitable for interaction with the replication-specific helicase. Other features of the structure are consistent with the polar contrahelicase mechanism of the protein. A model of the interaction between RTP and its cognate DNA is presented. PMID- 7867073 TI - The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases. AB - We report the identification of ligands for Tyro 3 (alternatively called Sky, rse, brt, or tif) and Axl (alternatively, Ark or UFO), members of a previously orphan family of receptor-like tyrosine kinases. These ligands correspond to protein S, a protease regulator that is a potent anticoagulant, and Gas6, a protein related to protein S but lacking any known function. Our results are reminiscent of recent findings that the procoagulant thrombin, a protease that drives clot formation by cleaving fibrinogen to form fibrin, also binds and activates intracellular signaling via a G protein-coupled cell surface receptor. Proteases and protease regulators that also activate specific cell surface receptors may serve to integrate coagulation with associated cellular responses required for tissue repair and growth, as well as to coordinate protease cascades and associated cellular responses in other systems, such as those involved in growth and remodeling of the nervous system. PMID- 7867074 TI - Phenotypic identification of specific and nonspecific suppressor T-cell populations involved in the in vivo response to alloantigen. AB - The monoclonal antibody 984.D4.6 (ma984) has been previously shown to recognize antigen-specific suppressor T-cells in an in vitro alloantigenic mixed-lymphocyte response system. In addition, an antiserum generated in rabbits to the N-terminal sequence of the nonspecific suppressor factor SIRS (soluble immune response suppressor) has been shown to block the suppressive activity of nonspecific, concanavalin A-activated suppressor cells. In the present studies we have used these antibodies to investigate the development of T-suppressor activity in mice immunized with alloantigen. These studies demonstrate the development of two populations of suppressor cells, one of which is antigen nonspecific and inhibitable with anti-SIRS and a second that is antigen-specific and sensitive to removal by lysis with ma984 plus complement. These populations of suppressor cells arise well after the peak of cytolytic T-cell activity in response to alloantigen indicating asynchrony in the development of the immune response to alloantigen. PMID- 7867075 TI - Mercuric chloride-induced programmed cell death of a murine T cell hybridoma. II. Opposite effect of interleukin-2 and interleukin-4. AB - In susceptible animals evidence is accumulating for a primary role for Th2 cells in the course of HgCl2-induced autoimmunity, and for a contribution of Th1 cells in the self-regulated phase of this disease. We have reported that incubation of 2B4.11 T cell hybridoma with HgCl2 induced programmed cell death. This paper shows that recombinant IL-2 significantly diminished HgCl2-induced 2B4.11 cell death. Although no effect was observed upon incubation with exogenous IL-4, we observed a significant protection by adding an anti-IL-4 monoclonal antibody to the culture. Accordingly, by RT-PCR we found the presence of IL-2 receptor encoding mRNA, and by cytofluorometry, the expression of the protein was detected only after exposure to HgCl2. Moreover, upon HgCl2 treatment, 2B4.11 cells were induced to produce IL-4. Altogether these findings showed that cytokine environment, IL-2, IL-4 otherwise defining the Th1/Th2 dichotomy, in conjunction with a chemical may differentially influence the fate of cell populations, death or survival. PMID- 7867076 TI - Unique order of the lymphocyte subset induction in the liver and intestine of mice during Listeria monocytogenes infection. AB - We investigated how NK cells, extrathymic T cells, and thymus-derived T cells are activated in mice during infection with an intracellular pathogen, Listeria (L.) monocytogenes. Although macrophages and granulocytes are known to be involved in the elimination of this pathogen in an early phase of infection, it was still controversial what type of lymphocytes are induced as effectors in subsequent phases. When mice were ip injected with 1 x 10(3) L. monocytogenes (a sublethal dose), a prominent increase in the number of mononuclear cells in the liver and spleen was induced. Phenotypic analysis revealed that serial induction of lymphocyte subsets, NK cells-->extrathymic T cells-->thymus-derived T cells, occurred in these organs. Extrathymic T cells were estimated to have intermediate CD3 and a high level of IL-2 receptor beta-chain on the surface (i.e., intermediate CD3 cells). These mice became free from infection after 2 weeks. In the case of oral administration, 1 x 10(3) L. monocytogenes increased the number of cells in the liver and the number of intraepithelial and lamina propria lymphocytes in the intestine. Phenotypic analysis also showed a sequential induction of lymphocyte subsets in the liver and the induction of extrathymic T cells in the intestine. Preelimination of intermediate TCR cells and NK cells by in vivo treatment with anti-LFA-1 mAb made mice susceptible to an ip injected sublethal dose of L. monocytogenes. These results reveal a unique order of lymphocyte induction during listerial infection and indicate that extrathymic T cells might be one of the important cells in achieving resistance against L. monocytogenes. PMID- 7867077 TI - Granulocyte-macrophage colony-stimulating factor and interleukin-4 differentially regulate the human tumor necrosis factor-alpha promoter region. AB - Regulation of TNF-alpha promoter activity by IL-2, IFN-gamma, GM-CSF, and IL-4 was examined in the U937 macrophage cell line and the MLA 144 T cell line. Using a transient transfection system, the full-length TNF-alpha promoter was examined for response to these cytokine signals. Only GM-CSF was able to consistently induce a twofold activation of the TNF-alpha promoter in the U937 cell line. GM CSF activation of the promoter region was further analyzed using a series of 5' truncations and site mutations of the AP-1, AP-2, and CRE sites of the promoter. The GM-CSF activation mapped to the region contained within the 95 base pairs upstream from the transcription start site (TSS) with the AP-2 site as a putative cis-acting sequence. IL-4 profoundly inhibited both basal and phorbol ester induced TNF-alpha promoter activity as well as protein production. Promoter inhibition by IL-4 required the 95-bp basal promoter sequence. PMID- 7867078 TI - The antitumor activity induced by the in vivo administration of activated B cells bound to anti-CD3 monoclonal antibody. AB - We examined the immunotherapeutic ability of activated B cells which bound to anti-CD3 monoclonal antibody (mAb) to enhance antitumor T cell immunity in vivo. A flow cytometric analysis revealed that LPS (lipopolysaccharide)-activated B cells (LPS blasts) expressed Fc receptor (FcR) which can bind to anti-CD3 mAb. LPS blasts were also stained with CTLA-4Ig, which can bind to costimulation molecules with high affinity, which suggested that LPS blasts expressed costimulation molecules on their surface. In an in vitro assay, T cells remarkably proliferated in the presence of LPS blasts and soluble anti-CD3 mAb, whereas this proliferation was blocked by the addition of CTLA-4Ig. In a model of metastasis established by the intravenous inoculation of melanoma cells, the in vivo administration of LPS blasts incubated with anti-CD3 mAb and followed by treatment with polyethylene glycol, to reinforce the binding, induced a low but significant antitumor activity against melanoma. The antitumor activity induced by the in vivo administration of LPS blasts which bound to anti-CD3 mAb was also detected in the spontaneously established model of metastasis. These results therefore suggest that the in vivo administration of activated B cells which bound to anti-CD3 mAb was able to enhance the antitumor T cell response against metastatic melanoma. PMID- 7867079 TI - Iron differentially modulates the CD4-lck and CD8-lck complexes in resting peripheral blood T-lymphocytes. AB - Clinical and experimental studies performed in situations of iron overload have demonstrated that iron impairs several T-cell functions. We have examined the effect of iron in the form of ferric citrate on the CD4-lck and CD8-lck complexes in view of the key role played by the tyrosine kinase p56lck in regulating T-cell functions. Ferric citrate was seen to differentially modulate the CD4-lck and CD8 lck complexes in resting peripheral blood T-lymphocytes (PBLs) cultured in the presence of this metal salt for periods of 20 to 24 hr. Thus, whereas ferric citrate invariably induced a marked decrease in the in vitro activity of the CD4 associated lck by three- to fourfold at 100 microM (P < 3 x 10(-5)), it did not affect significantly the in vitro activity of the CD8-associated lck, although modest decreases were observed in some experiments. Immunoprecipitation and subsequent lck-immunoblotting revealed that the marked decrease in CD4-lck activity induced by 100 microM of ferric citrate was due to a decrease in the amount of p56lck on CD4 immunoprecipitates. Furthermore, flow cytometry analysis showed a decrease in the surface expression of the CD4 molecule in iron-treated PBLs, as judged by a decrease in the mean fluorescence intensity (MFI), that was accompanied by a decrease in the percentage of CD4+ T-lymphocytes. In marked contrast, whereas the surface expression of the CD8 molecule was slightly decreased, the percentage of CD8+ T-lymphocytes remained constant. This differential effect of ferric citrate on the CD4+ and CD8+ T-cell subsets led to a marked decrease in the CD4/CD8 ratios in iron-treated PBLs after the 20- to 24 hr period (P < 0.001). The present results indicate that iron in the form of ferric citrate can modulate key molecules involved in the process of T-cell activation and therefore influence T-cell-mediated functions. PMID- 7867080 TI - IL-12 inhibits apoptosis induced in a human Th1 clone by gp120/CD4 cross-linking and CD3/TCR activation or by IL-2 deprivation. AB - The aim of our work was to study apoptosis as a possible mechanism of CD4+ lymphocyte depletion in AIDS patients and to test whether IL-12 could limit this phenomenon. As an in vitro model, we used a human IL-2-dependent Th1 clone from an uninfected individual. We found that CD4 cross-linking, obtained either by mouse anti-CD4 mAb plus goat anti-mouse or by recombinant gp120 plus anti-gp120 mAb, followed by activation with immobilized anti-CD3 or anti-TCR mAb, induced apoptosis at early times (15-25% apoptotic cells at 4 hr), whereas IL-2 deprivation required longer times (20-40 hr) to induce apoptosis. Both CD4 cross linking and IL-2 deprivation-induced apoptosis appeared to be PTK-dependent and were inhibited by either IL-2 or IL-12. Our data suggest that in vivo CD4/gp120 interactions could directly prime the apoptosis of Th1 lymphocytes and that IL-2 and IL-12 could be used to prevent this phenomenon. PMID- 7867081 TI - Disruption of intrathymic CD4-Ia interactions on immature CD4+CD8+ thymocytes results in diminished TCR expression on mature CD8+ T cell progeny. AB - Cell surface TCR expression by developing thymocytes is actively regulated during ontogeny. Whereas most immature CD4+CD8+ thymocytes express low levels of TCR alpha beta, mature CD4+ and CD8+ thymocytes express significantly higher levels of surface TCR. Low TCR expression on CD4+CD8+ thymocytes is due, at least in part, to inhibitory signals generated by CD4 interactions with MHC class II ligands in the thymus. In the present study we wished to determine whether levels of TCR expressed on mature thymocytes were also influenced by CD4-Ia interactions that had occurred on their CD4+CD8+ precursors. To do so, we examined TCR expression on mature CD8+ T cells from animals in which CD4-ligand interactions had been disrupted experimentally by in vivo administration of anti-CD4 mAb or by targeted disruption of an MHC class II gene. We found that TCR expression was significantly diminished on all mature CD8+ T cells from both anti-CD4 mAb treated mice and MHC class II-deficient animals. These results demonstrate that TCR expression by mature CD8+ T cells, as well as that of immature CD4+CD8+ thymocytes, is regulated by CD4-mediated signals acting on CD4+CD8+ thymocytes. Because the effects of disrupting CD4-Ia interactions on TCR expression by CD8+ T cells were independent of TCR specificity, these findings directly support the concept that CD4-CD8+ T cells arise from precursor CD4+CD8+ cells. PMID- 7867082 TI - Patterns of interferon-gamma mRNA expression in toxic shock syndrome toxin-1 expanded V beta 11+ T lymphocytes. AB - We have recently demonstrated that toxic shock syndrome toxin-1 (TSST-1), a staphylococcal exotoxin with superantigenic properties, is involved in the pathogenesis of septic arthritis. The aim of the current study was to characterize in detail the in vitro properties of TSST-1 with regard to T cell activation patterns. We demonstrate that TSST-1 preferentially expands murine V beta 11+ T lymphocytes and this expansion occurs equally well within CD4 and CD8 compartments. To analyze the functional properties of V beta 11+ T cells expanded in response to TSST-1, we have utilized a combined in situ hybridization and immunocytochemistry method. With this technique we show that TSST-1-stimulated V beta 11+ T cells are an important source of IFN gamma mRNA synthesis, suggesting that this cytokine may participate in superantigen-mediated septic arthritis. PMID- 7867083 TI - Multiple CTL specificities against autologous HIV-1-infected BLCLs. AB - The cellular immune response to HIV-1 has been well studied but, in many respects, remains incompletely defined. Although CTL specificities against highly conserved HIV-1 determinants as dictated by vaccinia/HIV-1 vector constructs have been described, much less is known regarding patient cellular reactivities against autologous cells infected with HIV-1. One of the main obstacles in characterizing this cellular reactivity has been the absence of a targeting system which accurately represents the HIV infected cell in vivo and is, at the same time, adaptable for in vitro assays. Through the use of two separate strategies aimed at increasing cellular CD4 expression, we were able to infect B lymphocyte cell lines (BLCLs) with multiple strains of HIV-1. HIV-1-infected BLCLs were recognized by autologous effector cells with cytolytic specificities against env, gag, or pol determinants. In addition, HIV-1-infected BLCLs were capable of eliciting in vitro CTL reactivities directed against env-, gag-, and pol-expressing targets. This cellular reactivity was mediated by CD8+ cells and was MHC Class I restricted, suggesting a classical CTL response. Since multiple antigens are recognized, an HIV-1-infected BLCL is a more natural representation of an in vivo cellular target than other available testing systems and should permit a more representative analysis of CTL responses during infection or following vaccination. PMID- 7867084 TI - Natural killer cells inhibit the development of autoantibody production in (C57BL/6 x DBA/2) F1 hybrid mice injected with DBA/2 spleen cells. AB - We investigated the role of natural killer (NK) cells in the development of autoantibody production in which (C57BL/6 x DBA/2) F1 (BDF1) hybrid mice were injected intravenously with spleen cells (SC) from parental DBA/2 mice (treated BDF1 mice). Treated BDF1 mice began to show an increase in serum anti-dsDNA antibody 2 weeks after injection, while the NK activity of their SC transiently increased initially in the first 1 to 2 weeks after injection, but subsequently decreased dramatically. Flow cytometric analysis suggested that this sequential change in NK activity correlated with the absolute number of host-derived NK1.1+ cells in SC from treated BDF1 mice. We demonstrated that the level of anti-dsDNA in serum is directly influenced by the level of NK activity in treated BDF1 mice. Depletion of NK cells by administration of anti-NK1.1 mAb accelerated the development of autoantibody production, whereas augmentation of NK activity by administration of poly-(I:C) inhibited the development of autoantibody production. This inhibitory effect of poly(I:C) was abolished by prior depletion of NK cells. Interestingly, suppression of autoantibody production was seen only when poly(I:C) was administrated within 1 week after injection of parental SC. Last, we demonstrate that adoptive transfer of interleukin-2 (IL-2)-activated NK cells had a protective effect against the development of autoantibody production. These findings imply that NK cells may have a protective role in lupus-like disease especially in its early stage. In addition, it opens up the possibility that adoptive immunotherapy with IL-2-activated NK cells can delay or even prevent the development of autoimmune disease. PMID- 7867085 TI - The role of peritoneal stromal cells in the survival of sIgM+ peritoneal B lymphocyte populations. AB - Peritoneal (PE) B cells, a large fraction of which belong to the B-1 subset (i.e., the CD5+ B cell lineage), exhibit unusual growth and/or survival characteristics. To evaluate if these characteristics reflect intrinsic properties of PE B cells or the support provided by a potentially unique peritoneal microenvironment, B cells from various organs were cultured on PE stromal cell monolayers. It was determined that sIgM+ PE B cell populations survive for notably long periods of time (at least 4 weeks) when cultured with PE stromal cells. Contact of PE B cells with stromal cell monolayers optimized B cell survival. Although expressing a similar spectrum of adhesion molecules as peritoneal stromal cells, splenic and bone marrow stromal cells were significantly inferior at supporting PE B cells. Increased survival of PE B cells was characterized by a significant but transient increase in proliferation and by an increase in the percentage of B220/CD45high/CD5+ PE B cells. PE stromal cell support of B cell populations did not extend to all B or even to all B-1 cell populations since survival of splenic B cells, only a minority of which belong to the B-1 lineage, or thymic B cells, a majority of which belong to the B-1 lineage, was not enhanced by culture on PE stromal cells. Results demonstrate: (a) a system for relatively long-term maintenance of mature B cells, (b) that the growth/survival of PE B cells is preferentially supported by PE stromal cells, and (c) that growth on PE stromal cells is a characteristic of peritoneal B cells but not necessarily of splenic B cells or B-1 cells from other organs. The suggestion that the local microenvironment contributes to unusual growth, survival, or anatomic distribution of B-1 cells is discussed. PMID- 7867086 TI - Different subcellular localization of cytochrome b and the dormant NADPH-oxidase in neutrophils and macrophages: effect on the production of reactive oxygen species during phagocytosis. AB - When neutrophils and macrophages phagocytose a prey, e.g., complement (C3b) opsonized yeast particles, the oxygen radical generating NADPH-oxidase is activated. In neutrophils, most of the production of oxygen metabolites occurred in an intracellular compartment, possibly in the phagolysosome. In contrast, no intracellular production could be detected in human macrophages. In these cells, the subcellular localization of the superoxide-generating NADPH-oxidase and associated cytochrome b was assessed in intact cells with indirect immunofluorescence and confocal laser scanning microscopy, and with subcellular fractionation, using centrifugation on Percoll density gradients. A dual localization of the cytochrome b as well as the dormant NADPH-oxidase activity in neutrophils was in agreement with earlier immunocytochemical, biochemical, and subcellular fractionation studies. Furthermore, most of the activity was recovered from the specific granules, whereas only a small fraction was retained in the plasma membrane. In contrast, the cytochrome b/NADPH-oxidase activity in macrophages localized primarily in the plasma membrane fraction. We suggest that the macrophages are incapable of producing reactive oxygen species intraphagosomally, due to an absence of a granule-localized pool of the membrane components of the NADPH-oxidase. PMID- 7867087 TI - Characterization and regulation of prostaglandin E2 receptors on normal and malignant murine B lymphocytes. AB - Prostaglandin E2 (PGE2) is a pleiotropic lipid molecule synthesized by macrophages, follicular dendritic cells, and fibroblasts, inhabitants of the B cell microenvironment. It is a potent regulator of B lymphocyte functions including activation and immunoglobulin class switching. To understand the effects of PGE2 on B lymphocyte function, the features of the putative PGE2 receptor on cells of the B lineage must be delineated. This receptor has not yet been characterized on B lymphocytes. Murine B cell lymphomas were used as a model to evaluate B lineage PGE2 receptors since they elevate intracellular cAMP in response to PGE2. Scatchard analysis indicates that the PGE2 receptor on both CH31 and CH12 exists in a single high-affinity state, with the CH12 B lymphoma possessing three times more receptors per cell compared to CH31. Interestingly, the PGE2 receptor is subject to regulation as a 20-hr LPS treatment increased PGE2 receptor number by two- to threefold on CH12 and CH31 B cell lymphomas, while dissociation constants remained similar. Finally, Scatchard analysis of normal murine splenic B lymphocytes demonstrates that they also possess high affinity receptors for PGE2. Treatment of normal B cells with IL-4 increased PGE2 receptor levels fourfold from approximately 50 to 200 sites/cell while the affinity of the receptor slightly decreased. These results are the first to describe the number and affinity of PGE2 receptors on cells of the B lineage. These findings also suggest that B lymphocyte-activating molecules such as LPS and IL-4 may enhance sensitivity to PGE2 by upregulating the number of PGE2 receptors on B cells. Moreover, these observations may be of importance in developing strategies to specifically control the spread of PGE2-sensitive B lymphomas. PMID- 7867088 TI - Mercuric chloride-induced programmed cell death of a murine T cell hybridoma. I. Effect of the proto-oncogene Bcl-2. AB - Mercuric chloride (HgCl2) as well as several drugs can induce T cell activation leading to systemic immune-mediated diseases in genetically susceptible individuals or rodents. T cell hybridomas represent a well-characterized model system for in vivo mechanisms of various stimuli-induced cell death. The cellular response to HgCl2 was examined using various T cell lines and particularly the murine T cell hybridoma 2B4.11. Exposure to HgCl2 induced both necrosis and apoptosis in a dose- and time-dependent way as demonstrated by DNA fragmentation analysis, flow cytometry of the whole cells and of isolated nuclei, and morphological examination. HgCl2-induced cell death was partly inhibited by cycloheximide. The expression of human Bcl-2 in 2B4.11 cells after transfection significantly prevented HgCl2-induced cell death but did not affect the susceptibility to apoptosis induced by an anti-CD3 epsilon mAb. Subcytotoxic doses of HgCl2 enhanced metabolic activity of Bcl-2 transfectants in contrast with mock-transfected cell line. Thus, we conclude that apoptosis is part of the cell death process induced by HgCl2 and that the ability of Bcl-2 to prevent the death of one particular cell line is stimulus-dependent suggesting the existence of different pathways leading to cell death. PMID- 7867089 TI - [Studies of the suppressive effect of cDNA RA538 on three human cancer cell lines]. AB - As previously reported, transfer of RA538 into parental esophageal cancer EC8712 cell line induced its terminal differentiation and apoptosis. To further study the biological effects of this cDNA, an expression plasmid containing an insert of the putative coding fragment (about 0.3kb) of RA538 and neo resistance gene was constructed (designated pRA538-0.3-neo) and transferred into three different human cancer cell lines: EC8712, HL60 and GLC, a cell line derived from an adenocarcinoma of the lung. After selection in G418-containing culture media, the growth rate, 3H-thymidine incorporation rate, cell morphology, colony-formation in soft-agar, and heterotransplantation into nude mice of the surviving cell populations were tested. In situ hybridization verified the uptake and expression of the 0.3kb fragment of RA538 in these G418 resistant cell populations. Significant reduction in growth rate and suppression of malignant phenotype were observed in all these cells in comparison with their parental cancer cell lines. PMID- 7867090 TI - [Expression of cDNA RA538 induces terminal differentiation and apoptosis of its parental malignant cell line in vitro]. AB - A full-length cDNA (RA538) was isolated from human esophageal cancer cell line EC8712 after retinoic acid treatment. An expression vector of this cDNA (pRA538) was cotransfected with the neo gene (pDORneo) into parental cancer cell line EC8712. The cell colonies obtained after selection in G418-containing culture medium showed very poor growth, reduced (by 68%-76%) 3H-TdR uptake and morphological changes characteristic of terminal differentiation and programmed cell death (apoptosis). In situ hybridization with RA538 probes revealed expression of mRNA of RA538 in the cytoplasm of the transfected cells. The cells transfected solely with pDORneo after G418 selection showed normal growth pattern and no RA538 expression. However, none of the control cells EC8712 survived the G418 selection. Thus the expression of cDNA RA538 has a similar effect on the esophageal cancer cell EC8712 as the retinoic acid does. PMID- 7867091 TI - [The phenotypic change of smooth muscle cells in the media of pulmonary intra acinar arteries during hypoxia]. AB - The phenotypic change of smooth muscle cells (SMCs) in the media of pulmonary intraacinar arteries (IAA) was observed in rats during hypoxia. From 3 to 40 exposure days, pulmonary arterial pressure (PAP) and right ventricular hypertrophy increased parallely. From 1 to 5 exposure days, SMCs still displayed the "contractile" phenotype, but the amount of intercellular collagen slightly increased. After 7 exposure days, some medial SMCs changed into the "fully" or "partially" "synthetic" phenotype with an excess of intercellular collagen. From 14 to 40 exposure days, other than some SMCs of partially "synthetic" phenotype, a great number of SMCs acquired the "contractile" phenotype characteristics, but the synthetic and secretive organelles and intercellular collagen were still more than those in the groups from 1 to 5 exposure days. Our results suggested that along with the prolongation of hypoxic exposure, the kinetic changes of SMC phenotype might not parallel with PAP change. PMID- 7867093 TI - [Study on the pelvic stomata and computer image processing]. AB - A medical image processing system attached to electron microscope was used to study the pelvic stomata of fetuses quantitatively. Two kinds of the mesothelial cells were found on the pelvic peritoneum of fetuses and mice, i.e. flattened and cuboidal cells. The pelvic stomata, arranged in clusters, only were located among the cuboidal cells with skewed distribution. Discrete scale of the pelvic stomata area varied greatly. The average area of a stoma was 10.00 +/- 9.44 microns2. Coefficient of variation was 94.40. Standard deviation and standard error were 9.44 and 0.98, respectively. Most of the pelvic stomata present were 1.34 microns2 to 32.11 microns2, and the maximum and the minimum areas of stomata were 43.4 microns2 and 0.8 micron2. The average percentage of the pelvic stomata was 7.2%. PMID- 7867092 TI - [Gene expression of EGFR, EGF and TGF alpha in human colonic carcinoma cell lines]. AB - Gene expression of epidermal growth factor receptor (EGFR), epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) in human colonic carcinoma cell lines (HT10, LST174 and Lovo) was studied by using Northern blot technique. Total RNAs were isolated from these cell lines, separated by 1% agarose gel electrophoresis, transferred onto a membrane and hybridized with EGFR, EGF and TGF alpha probes. EGF and EGFR mRNAs were found in all three cell lines, and TGF alpha mRNA was seen in LST174 and HT10 cell lines but not in Lovo. The results indicate that autocrine stimulation by growth factor exists in human colonic carcinoma cell lines and it may be one of the important causes for the uncontrolled growth of carcinoma cell. PMID- 7867094 TI - [Inhibitory effects of monomer T4 from Tripterygium wilfordii hook on cultured mesangial cells proliferation and IL-1 production]. AB - The cultured mesangial cells (MSc) went through three serial passages before being using. Quantitation of MSc growth rate was obtained by measuring the ratio of 3H-TdR uptake in a medium containing various concentrations of T4. IL-1 activity was tested by 3H-TdR incorporation in C57BL/c mice thymocytes. The results show that T4 inhibited MSc proliferation and IL-1 production. PMID- 7867095 TI - [Age-related differences of blood flow distribution in canine mandibular ramus]. AB - Blood flow distributions of canine mandibular rami in two different age groups were measured using the radioactive microsphere technique. The blood flow rates (ml/min/100g) of six regions of canine mandibular ramus in the infant group were 20.26 +/- 3.45, 10.70 +/- 2.69, 6.52 +/- 2.59, 8.92 +/- 2.47, 14.19 +/- 3.33 and 12.05 +/- 3.07. The blood flow rates of the correspondent regions of mandibular ramus in the adult group were 12.02 +/- 2.31, 8.65 +/- 2.02, 4.39 +/- 1.47, 6.07 +/- 1.28, 7.44 +/- 1.70, and 5.49 +/- 1.42. The blood flow rates of six regions of mandibular ramus in the infant group were all significantly higher than that of the correspondent regions of the adult group. The distribution patterns of blood supply to mandibular ramus are also not identical between the infant and the adult groups. The age-related differences of blood flow distribution of canine mandibular ramus reflects the intimate relation between the blood supply and growth of mandibular ramus. PMID- 7867096 TI - [Long-term follow-up of patients with patella resurfacing]. AB - Patellar resurfacing was performed by the authors. From 1983 to 1988, 19 cases (22 knees) with patello-femoral osteoarthritis were treated with this procedure in our hospital. Excellent and good results were recorded in 13 cases (59.1%) one year after operation, but were zero in the long-term follow-up (average 8.7 years) because of recurrent knee pain due to the wearing of the cortex of the femoral groove. Further operation was necessary for those cases, such as patellectomy or total knee replacement. Since 1991 Y-L-Q's type of patellofemoral replacement has been used in 11 cases in our department to alter the isolated resurfacing of the patella. The femoral groove was replaced with a metallic implant that allows sliding of a polyethylene patella to prevent the wearing of the femoral cortex. Preliminary results are good. PMID- 7867097 TI - [Ocular manifestations of patients with gangliosidosis]. AB - This paper describes the ophthalmological findings in 4 patients with gangliosidosis (GLS). The diagnosis was verified by assaying hexosaminidase A and beta-galactosidase activities with marked deficiency. The presence of a cherry red spot at the macular region, macular degeneration and atrophy of the optic disc were the main ocular manifestations. The ocular pathological changes seen under light and electron microscopy and the inherited error of metabolism of ganglioside are discussed. PMID- 7867098 TI - [Expression of HPV16E6 gene and preparation of monoclonal antibody against the expression product]. AB - The recombinant plasmid PAS1-HPV16E6 containing the HPV16E6 gene was expressed in E. coli AR120 under nalidixic acid induction. A 19KD expression protein was isolated, purified and identified. Mice were immunized with the purified E6 expression protein. A murine hybridoma, RAC6, was obtained by fusing splenic cells from an immunized BABL/c mouse with mouse myeloma cell line SP2/0-Ag14 cells, followed by screening in HAT medium, cloning and recloning in methyl cellulose. The hybridoma RAC6 stably produces specific monoclonal antibody against the E6 expression protein. PMID- 7867099 TI - [The effects of extracellular matrix on Sertoli cells of rats in vitro]. AB - This study was performed to observe the effects of extracellular matrix (ECM) on Sertoli cells attachment, spreading and morphology in vitro. The ECM used were FN and LN and biomatrix isolated from the liver and lung. The results showed that FN and LN promoted Sertoli cell attachment and spreading. The Sertoli cells grown on the biomatrix isolated from the lung assumed a columnar shape like that seen in vivo. The cells grown on biomatrix from the liver did not. PMID- 7867100 TI - [Mapping of full-length murine renin-2 gene]. AB - A 24kb fragment containing full-length renin-2 gene and its flanking sequence was obtained by digesting the pKG-R2D with XhoI. This fragment was cleaved with single enzyme (EcoRI, KpnI and BamHI), and combined enzymes (EcoRI/KpnI, KpnI/BamHI and BamHI/EcoRI), respectively. The digests were electrophoresed on 0.8% agarose plates and transferred onto NC membranes. Radioactive probes of 735bp and 1400bp, templates of which were from half and full-length of renin-1 cDNA, respectively were used for Southern hybridization. On the basis of electrophoresis and hybridization patterns, a restriction map was constructed in this paper. PMID- 7867101 TI - [Marchiafava-Bignami disease]. AB - One case of subacute development of Marchiafava-Bignami disease (MBD) is reported. The clinical characteristics and pathogenetic aspects of the disease are discussed. The usage of MRI in the diagnosis of MBD before the patient's death was the first ever in China. PMID- 7867102 TI - [The adherence reaction between Candida and cultured cell in vitro]. AB - The adherence reaction between Candida and cultured cells in vitro was studied. After the comparison between two fungal phases, two different ratios of cells to fungi and two different incubation temperature, we found that the better adhesion condition is at 37 degrees C, with a concentration of cell to fungi of 1:200 and with the Candida albicans in the germ tube phase. We also found 4 different materials that could inhibit C. albicans adherence. PMID- 7867103 TI - [Study on the invasive properties of cloned human nasopharyngeal carcinoma CNE2Z variants using organ culture in vitro]. AB - Using limiting dilution assay, variants were cloned from the CNE-2Z cell line. The variants CNE2L2, CNE2H2, CNE2L4 and CNE2M2, with cell electrophoresis rates which differed greatly, were assayed for their invasive capabilities by observing their ability to invade preculture embryonic chicken heart fragment (PHF) in organ culture using a gyrotory shaker system. The results indicated that CNE2L2 variant cells invaded 9-day-old chicken embryonic heart fragments at a rate significantly higher than those seen using CNE2L4 and CNE2M2 in 7-day assay. Computer image analysis showed that the CNE2L2 cells occupied 80.2% of the PHF area much greater than that occupied by CNE2L4 (46.5%) or CNE2M2 (36.5%). This experiment also showed that the electrophoresis rate of the CNE2Z variants was positively related to their invasive capabilities in vitro. PMID- 7867104 TI - Allergy, anaphylaxis and anaesthesia. PMID- 7867105 TI - Combined technique for cardiac anaesthesia. PMID- 7867106 TI - Canadian anaesthetists' overseas responsibility. PMID- 7867108 TI - Comparison of selection of preoperative laboratory tests: the computer vs the anaesthetist. AB - HealthQuiz II (HQII) is a computerized history-taking device which can be used by patients before anaesthesia and surgery. HealthQuiz II provides a summary of symptoms, a modified ASA Classification, and a list of suggested laboratory tests. Developed at the University of Chicago, the device has not been evaluated in Canada. The purpose of this study was to compare preoperative evaluation and selection of laboratory tests by a group of Canadian anaesthetists using traditional methods versus using HealthQuiz II. Twenty-seven anaesthetists from three (Western) Canadian University teaching hospitals participated in the study. The subjects were male, aged between 30-50 yr, trained in Canada and practicing in Calgary, Edmonton and Vancouver. They were asked to self-evaluate and select laboratory tests and then to complete the HQII protocol, the day before a proposed mock operation. Results of this comparison showed that the ASA scores assigned by HQII were higher for 11 subjects and lower for two. Eight anaesthetists thought HQII asked questions which they omitted while five thought HQII overlooked items. Thirteen anaesthetists believed HQII would be a useful adjunct to their practice. Only ten anaesthetists requested any tests while HealthQuiz II suggested tests for 23 subjects, with an average of 1.9 tests/subject (anaesthetists) vs 5.4 tests/subject (HQII). The total cost of tests selected by anaesthetists was $272.15 in contrast with $1,513.20 for those suggested by HQII. We conclude that rationale for test selection may have contributed to the difference in number and costs of tests. PMID- 7867107 TI - Drug allergies in the surgical population. AB - Many patients claim to have drug allergies. However, the signs and symptoms of "allergic reactions" are seldom documented and the drug allergies are rarely properly assessed. The goal of this study was to determine the incidence of claimed "drug allergies" in a surgical population. After obtaining institutional approval, the study was carried out at five hospitals affiliated with Dalhousie University. Patients were interviewed by the investigators during the preoperative anaesthetic evaluation over six months and all signs and symptoms of drug reactions were recorded. The validity of the claimed allergy was based on the history. The allergies were assigned to one of three groups: (1) High probability of an allergic reaction: one or more of the signs and symptoms typical of an immunological reaction, with or without a family history, or a history of atopy; (ii) Low probability of an allergic reaction: signs and symptoms of the reaction were predictable reactions or side effects of the drug, without the occurrence of reactions mentioned above; or (iii) Unknown status: no information concerning the reaction of history was available. Of 1818 adult and paediatric patients (914 female/904 male) interviewed, 511 (28.1%) claimed to have one or more drug allergies (a total of 671 allergies). More women than men claimed to have drug allergies (60.3% vs 39.7%) and there was a positive correlation between age, number of medications and reported drug allergies. Antibiotics (50%), opioids (27%), non-steroidal anti-inflammatory agents (10%), and sedatives (5%) accounted for 92% of all claimed drug allergies. Overall, 50% of claimed allergies had a high probability of true allergic reactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867109 TI - Sedation for upper gastrointestinal endoscopy: a comparison of alfentanil midazolam and meperidine-diazepam. AB - The authors studied the efficacy and cost of substituting sedation using midazolam and alfentanil for the existing regimen of diazepam and meperidine in patients requiring upper gastrointestinal endoscopy. Sixty consenting subjects were randomized to receive either meperidine 50 mg with diazepam approximately 90 micrograms.kg-1 (Group D) or alfentanil 250 micrograms with midazolam approximately 50 micrograms.kg-1 (Group M). Endoscope insertion time, patient acceptance, apnoeic or desaturation episodes were noted by a physician observer. Pulse oximetry was used to monitor heart rate and oxygen saturation (SpO2) during endoscopy. Subjects performed four-choice reaction time (4CRT) tests before, 30 and 60 min after endoscopy, and were assessed for nausea or dizziness and their ability to stand and walk. During endoscopy, insertion time was shorter (84 +/- 45 sec vs 122 +/- 83 sec, P < 0.03) and fewer aversive movements occurred (0.4 +/ 0.6 vs. 1.7 +/- 2.4, P < 0.005) in Group M than Group D. No subject in either group suffered any apnoea or prolonged desaturation requiring supplemental oxygen. Irrespective of treatment group, greater decreases in SpO2 (6.1 +/- 3.4% vs 3.6 +/- 2.2% P < 0.001) occurred in subjects > 45 yr of age than in subjects < or = 45 yr. During recovery 4CRT values at 30 min after endoscopy were longer (723 +/- 226 msec vs 594 +/- 139 msec, P < 0.005) in Group M than in Group D but not after 60 min. It was concluded that the small differences in endoscopy conditions and greater sedation during the first 30 min of recovery did not justify the additional cost of using midazolam and alfentnil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867110 TI - Recovery characteristics following induction of anaesthesia with a combination of thiopentone and propofol. AB - The purpose of this study was to determine the rate and quality of recovery when general anaesthesia was induced with a mixture of thiopentone and propofol, compared with thiopentone or propofol alone. Sixty ASA class I and II women scheduled for out-patient laparoscopic surgery underwent induction of anaesthesia with either (i) thiopentone, (ii) propofol, or (iii) a mixture of the two, in a randomized, double-blind fashion. Anaesthesia was then maintained using nitrous oxide, isoflurane and fentanyl. A psychometric test was administered before and after surgery, and the time taken to reach a series of recovery milestones was noted. Patients were discharged as soon as they were ambulant and had satisfactory control of pain and nausea with oral agents. They were telephoned at 24-48 hr later, and asked to rate their experience of a list of side effects on an ordinal scale. Patient groups were demographically comparable and underwent surgery of the same duration. Those receiving thiopentone were discharged after a mean time of 3 hr 25 +/- 58 min (SD). The corresponding figures for propofol and the thiopentone/propofol mixture were 2 hr 40 min (+/- 49) and 2 hr 48 min (+/- 68) respectively. The recovery time between thiopentone and the other two regimes was different (P < 0.05). All three groups experienced equally frequent and severe nausea, headache, tiredness and other side effects during the next 24 hr. It is concluded that induction with a mixture of thiopentone and propofol leads to a similar rate and quality of recovery to that of propofol above.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867112 TI - Accelerated onset of vecuronium neuromuscular block with pulmonary arterial administration. AB - The purpose of this study was to determine the onset times of vecuronium neuromuscular block administered into either the central circulation or a peripheral vein. One hundred and twenty adult patients with a pulmonary artery (PA) catheter were randomly divided into one of three groups with respect to the routes of vecuronium administration (n = 40 in each group). Anaesthesia was induced with midazolam 2.5 mg iv and fentanyl 10-50 micrograms.kg-1 iv and maintained with intermittent doses of fentanyl 50 micrograms iv and nitrous oxide 60-70% in oxygen. After immobilization of the forearm in a splint, the ulnar nerve was stimulated supramaximally every 12 sec. The resulting force of the evoked thumb twitch was recorded (Myograph 2000, Biometer, Denmark). The times from the injection to the first depression of twitch response (latent onset) in patients given vecuronium 0.08 mg.kg-1 into the pulmonary artery, the right atrium, and a peripheral vein on the hand were 58.0 +/- 19.5, 71.5 +/- 17.1, and 82.4 +/- 18.0 sec (mean +/- SD), respectively. The latent onset of neuromuscular block occurred sooner in patients given vecuronium into the central vein than when administered into a vein on the hand (P < 0.01). In comparing the patients given vecuronium into the central vein, the onset times to 95% twitch depression (onset) were 152.3 +/- 40.7 and 168.2 +/- 35.5 sec. The onset of block was found to be faster when vecuronium was administered into the pulmonary artery than into the right atrium (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867111 TI - Localized hypothermia influences assessment of recovery from vecuronium neuromuscular blockade. AB - The purpose of this study was to determine the extent to which localized hypothermia of a monitored extremity alters the assessment of recovery from vecuronium-induced neuromuscular blockade. Bilateral integrated evoked electromyographic (IEMG) responses were measured in the ulner distribution of 14 anaesthetized patients who had differing upper extremity temperatures as measured at the adductor pollicis to determine whether localized hypothermia alters the clinical assessment of spontaneous recovery from vecuronium-induced neuromuscular blockade. All patients received general anaesthesia with thiopentone, N2O/O2 and opioid; 11/14 patients received isoflurane for blood pressure control. Bilateral adductor pollicis, oesophageal and ambient temperatures, and IEMG evoked response (t1) expressed as percent unparalyzed control were recorded during the anaesthetic. The difference in evoked response between the warmer and the colder upper extremity was calculated at 25%, 50% and 75% spontaneous recovery from neuromuscular blockade in the warm extremity. Differences in temperature between extremities ranged from 0.2-11 degrees C. The difference in IEMG-evoked response between extremities was proportional to the difference in temperature, and there was a direct correlation (r = 0.78) between IEMG response and extremity temperature; IEMG response was absent when extremity temperature was less than 25 degrees C. We concluded that localized hypothermia in the monitored extremity decreases the IEMG-evoked response to vecuronium neuromuscular blockade; the greater the temperature decrease, the less the evoked response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867113 TI - Regional anaesthesia for circumcision in adults: a comparative study. AB - Penile block (PB) in adults is not a well-recognized technique. The aim of this study was to compare, in a randomized prospective manner, five different techniques of PB in 250 adults undergoing circumcision with regard to anaesthetic quality, complications and postoperative analgesia. Patients were divided into five groups (50 per group) according to the technique used: Group A--"10, 30-13, 30" approach; Group B--the subpubic approach; Group C--subcutaneous ring block; Group D--a combination of frenulum infiltration and the "10, 30-13, 30" approach; Group E--a combination of frenulum infiltration and the subpubic approach. The number of failed blocks in Groups A and B (41 and 43 respectively) was greater than in Groups C, D and E (2, 3 and 5 respectively) (P < 0.001). The five groups did not differ with regard to adverse effects or time until the onset of postoperative pain when the blocks were successful. It is concluded that good surgical anaesthesia, a low rate of adverse effects and prolonged postoperative analgesia can be achieved by the use of either subcutaneous ring block or a combination of dorsal nerve block (using the "10, 30-13, 30" or the subpubic approach) and infiltration of the frenulum. These approaches to the PB are effective anaesthetic techniques for circumcision in adults. PMID- 7867114 TI - Nicardipine and verapamil attenuate the pressor response to laryngoscopy and intubation. AB - In a prospective, double-blind study, we compared the efficacy of iv nicardipine hydrochloride and verapamil hydrochloride in attenuating the cardiovascular responses to laryngoscopy and tracheal intubation, in 45 patients undergoing elective surgery with general anaesthesia. Patients were allocated randomly to one of three groups of 15 patients. Patients in Group I received saline while those in Groups II and III received nicardipine hydrochloride, 0.03 mg.kg-1 or verapamil hydrochloride, 0.1 mg.kg-1 iv three minutes before laryngoscopy and intubation. Patients in Group I showed the greatest increase in SBP 25.4 +/- 2.2 2.2 mmHg and HR 35.7 +/- 3.8 beats.min-1 at one minute after intubation (P < 0.001), and these changes persisted throughout the study period albeit with decreasing magnitude. After drug administration, patients in Groups II and III demonstrated increases in HR of 26 +/- 2.4 and 15.1 +/- 2.2 beats.min-1 and decreases in SBP of 24.8 +/- 2.0 and 18.8 +/- 2.4 mmHg respectively (P < 0.001). It is concluded that nicardipine and verapamil are effective in attenuating pressor responses to laryngoscopy and intubation but did not control the tachycardia. PMID- 7867115 TI - Anaesthesia for coronary artery bypass surgery supplemented with subarachnoid bupivacaine and morphine: a report of 18 cases. AB - We report our experience with general anaesthesia (GA) supplemented with subarachnoid bupivacaine and morphine for coronary artery bypass surgery (CABG) in 18 patients. Fifteen patients were male, and mean age was 62 yr. Anaesthesia (GA) was induced with alfentanil 97 +/- 22 micrograms.kg-1 and midazolam 0.04 +/- 0.02 mg.kg-1 supplemented with a muscle relaxant, and maintained with isoflurane (0.25-0.5%) in oxygen throughout surgery. Spinal anaesthesia (SA) was then performed at a lumber level using hyperbaric bupivacaine (23-30 mg) and/or lidocaine (150 mg) with morphine (0.5-1 mg). Pooled data showed the following haemodynamic results (P < 0.05). Induction of GA produced a decrease in mean arterial pressure (MAP). Addition of SA produced a decrease in heart rate. Heart rate and MAP did not change with sternotomy. Phenylephrine support of arterial blood pressure was used at some time during operation in 17 patients. Supplementation of GA was minimal. Patients received 2.7 +/- 0.7 coronary grafts. Operating room time was 3.9 +/- 0.6 hr. Postoperative analgesic requirements were minimal, and in half of the patients tracheal extubation occurred on the day of surgery. Complications included one myocardial infarction, one resternotomy, a metabolic encephalopathy in a dialysis-dependent patient, and one case of herpes labialis. No patient recalled intraoperative events. Combined GA with SA may be an effective technique for CABG surgery. Further study of the cardiovascular, neurological and metabolic effects of the technique is required. PMID- 7867116 TI - The use of an endotracheal ventilation catheter for jet ventilation during a difficult intubation. AB - This case report describes the use of an endotracheal ventilation catheter (ETVC) to provide prolonged intraoperative jet ventilation, reintubation and the maintenance of tracheal access following extubation. It emphasizes that excellent oxygenation and ventilation can be achieved but such management can be complicated by a pneumothorax even when the risks are minimized. A 43-yr-old man presented for possible pulmonary sleeve resection. Placement of a double lumen endotracheal tube (DLT) by direct laryngoscopy was unsuccessful due to the inability to visualize the glottis. A 7.5 mm endotracheal tube (ETT) was successfully introduced over a fibreoptic bronchoscope (FOB). An ETVC was passed, permitting manually cycled jet ventilation while general intravenous anaesthesia and muscle relaxation were maintained. The ETT was then withdrawn over the ETVC and jet ventilation continued for approximately 90 min, while attempts at placing a DLT over a now malfunctioning FOB continued. These attempts were eventually abandoned and the patient was returned to the post-anaesthesia care unit (PACU) haemodynamically stable. The trachea was extubated over the ETVC, which remained in situ. A pneumothorax was noted on the postoperative chest x-ray. This case illustrates prolonged intraoperative jet injection via a "jet stylet" with satisfactory ventilation and oxygenation but complicated by a pneumothorax. Also it illustrates a strategy for the management of a "difficult extubation." PMID- 7867117 TI - Percutaneous transtracheal jet ventilation for paediatric endoscopic laser treatment of laryngeal and subglottic lesions. AB - Percutaneous transtracheal high frequency jet ventilation (TTJV) in adults is frequently used during anaesthesia for laryngeal microsurgery. It provides excellent surgical operating conditions and safety for the patient. The technique has not been evaluated in infants and children. Accordingly, we studied 16 infants and children (mean age 5.5 +/- 3.8 yr, range 6 wk-12 yr) who underwent 28 consecutive endoscopic procedures with laser microsurgery of the glottic or subglottic space under general anaesthesia using a TTJV technique. All patients had a severe obstructive lesion of the larynx and/or upper trachea. The mean duration of the procedure was 70 +/- 27 min (range 30-140 min). Indications for TTJV were: subglottic stenosis: 5, haemangioma: 4, laryngeal papillomatosis: 5, pharyngeal cyst: 1, laryngomalacia: 1. Adequate control of the airway and satisfactory gas exchange were obtained in all cases. Surgery was performed without being impeded by anaesthetic equipment. Three complications occurred: one extensive surgical emphysema; one bilateral pneumothorax; one severe vagus induced cardiovascular depression. Prompt and complete recovery without sequelae followed appropriate treatment. In 32% of the cases, the children were outpatients and in about half of the procedures (13/28) they left the hospital between the first and the third day. We conclude that percutaneous transtracheal jet ventilation is effective in paediatric endoscopic surgery. Procedures that might otherwise require a tracheostomy can be performed safely with this minimally invasive technique. Adequate indications and appropriate understanding of the technique and its potential problems are required for its correct application and successful use. PMID- 7867118 TI - Unsuspected tracheal rupture in blunt thoracic trauma. AB - The purpose of this report is to describe the discovery and management of an unanticipated injury during fibreoptic tracheal intubation. A 23-yr-old man sustained blunt cervical, thoracic and abdominal trauma in a motor vehicle accident. He was brought to the operating room for urgent management of his abdominal and cervical spine injuries. Examination of his airway during awake fibreoptic tracheal intubation revealed an unexpected tracheal injury. Surgical repair of the trachea was uneventful. The diagnosis and airway management of tracheal rupture are discussed. This case illustrates the importance of a full diagnostic examination during invasive anaesthetic procedures such as tracheal intubation. PMID- 7867119 TI - A comparison of sevoflurane with halothane, enflurane, and isoflurane on bronchoconstriction caused by histamine. AB - This study was conducted to assess the effect of sevoflurane on lung resistance and compliance, and its responsiveness to histamine. We studied eight dogs to compare the effect of sevoflurane, isoflurane, enflurane, and halothane on bronchoconstriction caused by histamine. Baseline values of pulmonary resistance (RL) and dynamic pulmonary compliance (Cdyn) were measured prior to administration of histamine. Histamine (2, 4, and 8 micrograms.kg-1) were administered iv, and the values of RL and Cdyn at the time of peak effect were recorded. Under 1 or 2 MAC anaesthesia, sevoflurane as well as the other three anaesthetics had no bronchoactive effects. The four anaesthetics, including sevoflurane, demonstrated inhibitory effect on increases in RL and decreases in Cdyn caused by histamine. At 1 MAC anaesthesia, % changes in RL caused by 2, 4, or 8 micrograms.kg-1 of histamine were 38 +/- 11, 85 +/- 21, or 132 +/- 24% (mean +/- SE) for halothane, and 65 +/- 11, 132 +/- 15, or 172 +/- 19% for sevoflurane, respectively. Sevoflurane was less effective than halothane in preventing increases in RL. In preventing decreases in Cdyn, sevoflurane was less effective than halothane only at 8 micrograms.kg-1 of histamine under 1 and 2 MAC anaesthesia. There was no difference in attenuating effect on changes in RL and Cdyn between sevoflurane and isoflurane or enflurane. We concluded that sevoflurane was less potent than halothane in attenuating changes in RL and Cdyn in response to iv histamine. PMID- 7867120 TI - Anaesthesia for caesarean delivery of a malignant hyperthermia susceptible parturient. AB - The anaesthetic management for Caesarean delivery of a parturient with a strong family history of malignant hyperthermia (MH) is presented. Before surgery an anaesthetic machine that was in regular use was prepared by replacing all rubber or disposable components and flushing with O2 at 10 L.min-1 for one hour. Dantrolene prophylaxis was not used, and the patient received a bupivacaine and fentanyl spinal anaesthetic. Hypotension was treated with ephedrine. Current management of the MH patient no longer mandates a dedicated vapour-free machine, dantrolene is not indicated as pre-treatment, and amide local anaesthetics are considered safe. The role of vasopressors and ergot preparations is less clear. PMID- 7867122 TI - Same day consent for anaesthesia research. PMID- 7867121 TI - The experiential curriculum: an alternate model for anaesthesia education. AB - The shift to direct entry into residency training from medical school for all graduates will offer new challenges for anaesthesia training programmes. In this paper we argue that it also offers us an opportunity to re-evaluate our current approach to anaesthesia education. Emphasis in the residency programmes should be to provide trainees with clinical experiences and stimulation that will develop the required traditional competencies. It should also cultivate competency in clinical decision-making, intuition and judgement. Our purpose is to generate discussion by proposing an alternate curriculum model, the experiential curriculum. The basic premise is that learning is a process and outcome is to a large extent related to what the learner does. The process begins with an experience that provides for observation and reflection. Integration of the thoughts provides the basis for executing either existing or new actions. In the experiential curriculum residency training and learning are enhanced by documenting and critically evaluating the experiences to which the resident is exposed. Included within such a structured programme are the methodologies of problem-based and evidence-based learning. Faculty development will be required to help the resident pursue these skills of self-evaluation and efficient learning. We believe that incorporation of an experiential curriculum into the residency training programme will achieve the goals listed above and allow maturation of the process of lifelong learning. It will also allow greater achievement of the application of new information to one's practice. PMID- 7867123 TI - LMA masks and children. PMID- 7867124 TI - Glossopharyngeal nerve block for tonsillectomy or uvulopalatopharyngoplasty. PMID- 7867126 TI - Posterior lumbar plexus block. PMID- 7867125 TI - Epidural and intravenous fentanyl. PMID- 7867127 TI - Control of Salmonella infections in animals and prevention of human foodborne Salmonella infections. WHO Consultation. AB - In many countries the incidence of human salmonella infections has markedly increased in recent years. To discuss recent developments and current understanding on the control of salmonella infections in animals, WHO organized a Consultation on the Control of Salmonella Infections in Animals: Prevention of Foodborne Salmonella Infections in Humans, held in Jena, Germany, on 21-26 November 1993. The present article summarizes the recommendations made by the participants on the pathoimmunogenesis, diagnosis, epidemiology, and control of salmonella infections and contaminations in animal production. PMID- 7867128 TI - Destruction of variola virus: memorandum from a WHO meeting. AB - This Memorandum discusses the fate of variola virus stocks which have been kept in two WHO Collaborating Centres, as well as cloned DNA fragments of variola virus genome, smallpox vaccine, and seed vaccinia virus for the production of this vaccine. General and specific recommendations are given concerning destruction of variola virus; storage, distribution and handling of cloned DNA fragments of variola virus genome; and about stocks of smallpox vaccine. PMID- 7867129 TI - Emerging infectious diseases: memorandum from a WHO meeting. AB - A meeting of international experts exchanged information on recent activities dealing with new, emerging and re-emerging diseases, discussed ways of responding to this problem and to other communicable disease threats, and reviewed WHO's activities and role in this area. This Memorandum summarizes the various presentations and concludes with the recommendations and specific tasks for action at every level. PMID- 7867130 TI - Zoonotic tuberculosis (Mycobacterium bovis): memorandum from a WHO meeting (with the participation of FAO). AB - In view of the considerable and continuing public health significance of Mycobacterium bovis infection in humans and animals, WHO convened a meeting on zoonotic tuberculosis in Geneva in November 1993. The participants at the meeting reviewed the human and animal tuberculosis situation worldwide, discussed the zoonotic aspects of M. bovis infection in United Republic of Tanzania and Zambia, exchanged views on methodologies in epidemiology, immunology and molecular biology, and identified areas for further research and intersectoral collaboration. A project protocol to investigate the zoonotic aspects of bovine tuberculosis was elaborated by the group and included in their report. This Memorandum is a summary of the full report of the meeting. PMID- 7867131 TI - Safety of one 52-mumol (50,000 IU) oral dose of vitamin A administered to neonates. AB - A placebo-controlled trial was carried out among 2067 Indonesian neonates to assess the safety of administering one oral 52-mumol (50,000 IU) dose of vitamin A. Infants were assessed for potential acute side-effects before and throughout 48 hours after the dose. The first 965 infants were examined by cranial ultrasound before and at 24 hours after dosing to rule out intracranial haemorrhage and determine the resistive index (RI) of the anterior cerebral artery using duplex Doppler. Groups were comparable at the baseline. A bulging fontanelle occurred in the control and vitamin A groups, respectively, among 2.7% and 4.6% of the infants at 24 hours, and 2.4% and 4.5% of the infants at 48 hours. The groups did not differ in any other sign or symptom assessed. No infant developed intracranial haemorrhage. Mean RI values were normal and not different between groups at baseline or at 24 hours. Mean RI fell during the 24 hours, as normally occurs; the mean decrease was nearly identical in the two groups. A bulging fontanelle was not associated with increased rates of any sign or symptom or with an increase in RI. The 52-mumol dose of oral vitamin A may cause a small increase in intracranial volume in a small proportion of infants, but no increase in intracranial pressure. Acute side-effects following this intervention were rare and mild. PMID- 7867132 TI - Growth and nutrition patterns of infants associated with a nutrition education and supplementation programme in Gaza, 1987-92. AB - Since 1986, the 28 government community health centres providing primary care in Gaza have paid special attention to growth monitoring, nutrition education, and routine vitamin and iron supplementation in infancy. In 1987-88, 1989 and 1992, respectively, the nursing staff in five of these centres monitored the growth and feeding patterns of 2222, 1899, and 1012 children aged up to 15 months. The growth measures of children aged up to 6 months were similar to standard growth charts, but subsequently deficiencies developed in the study children. There were no differences between the patterns for males and females. Infants from upper socioeconomic categories had growth patterns that were closest to the norm, but this was associated with feeding and supplementation differences. There was improvement in the growth and feeding patterns of the 1989 and 1990-92 birth cohorts compared with the 1987-88 group and with the standard. Feeding patterns showed high levels of compliance with nutrition guidance. Growth monitoring, staff and maternal education, and supplementation with vitamins and, especially, iron were associated with marked improvements in feeding patterns and the growth status of children aged 3-15 months. PMID- 7867133 TI - Evaluation of the safety of domestic food preparation in Malaysia. AB - Food-handling practices were studied in 119 and 158 households, respectively, in an urban and a rural community in Peninsular Malaysia. Hazard analyses, including microbiological analysis of foods, were carried out in two households in each community and in a house that prepared food for distribution in the urban area. Kitchen hygiene was generally acceptable, although rated "poor" in some instances in the rural area. Food prepared for lunch was usually sufficient for dinner also, the leftover items being stored at ambient temperature until required. In the house that prepared food for distribution, breakfast was prepared during the evening, stored at ambient temperature overnight, and reheated before sale the next morning. There was a local preference for cooking food at temperatures close to boiling point; this reduced the numbers of vegetative cells but not those of spores. In some stored foods the populations of Staphylococcus aureus, Bacillus cereus and mesophilic aerobic bacteria increased, the last-mentioned reaching spoilage levels. Reheating reduced the populations of proliferating bacteria in most foods to acceptable levels but would not have destroyed heat-resistant enterotoxins. Because of their importance in combating acute bacterial foodborne disease, the control of the temperature and time factors during the cooking and storage of food should receive special attention in education on health and food safety. PMID- 7867134 TI - Childhood vaccination coverage in Italy: results of a seven-region survey. The Italian Vaccine Coverage Survey Working Group. AB - In Italy few data exist on vaccination coverage and timeliness. We therefore carried out cluster surveys on 12-23-month-olds in nine Italian cities and regions using standard Expanded Programme on Immunization methodology. The study areas accounted for 40% of all live births in Italy in 1991. Coverage levels for the third dose of diphtheria and tetanus toxoids and for oral poliovirus vaccine, which are mandatory, exceeded 90% in all but one area. However, less than two thirds of the children had completed the primary vaccine series by their first birthday. The commonest reason for failure to complete the series in time was that the child had been sick and was not brought for vaccination. For the two optional vaccines (pertussis and measles) coverage was much poorer, ranging from 8% to 71% for pertussis and from 9% to 53% for measles. The commonest reason given by the mothers for pertussis non-vaccination was that they had been advised against it, while for measles the commonest reasons were that the child was sick and that they had been advised against it. These findings suggest that although coverage for the mandatory vaccines is high, coverage for pertussis and measles is very low. Additional education of physicians and mothers is needed concerning the true contraindications for vaccination. Also, in the absence of legislation making pertussis and measles vaccines mandatory, greater efforts are needed to convince physicians and the public about the benefits of their use. PMID- 7867135 TI - Management of childhood pneumonia by traditional birth attendants. The SEARCH Team. AB - In a field trial in Gadchiroli, India, we trained 30 paramedical workers (PMWs), 25 village health workers (VHWs) and 86 traditional birth attendants (TBAs) from 58 villages to diagnose childhood pneumonia and treat it with sulfamethoxazole+trimethoprim. Continued training, the development of a breath counter, and educative supervision progressively reduced errors in case management made by the TBAs. Over the 3.5-year period 1988-91, 2568 attacks of childhood pneumonia were managed and the case fatality rate was 0.9%, compared with a rate of 13.5% in the control area. The case fatality rates for the three types of worker were similar. The TBAs were superior to the other workers in terms of their availability, outreach, access to neonates, and cost. Satisfaction with the VHWs, and PMWs was expressed by 85%, 69% and 18% of users, respectively. In the intervention area the mortality rate attributable to pneumonia among neonates declined by 44% (P < 0.01) while the total neonatal mortality fell by 20%, presumably because of the involvement of TBAs in the control of acute respiratory infections (ARI). If adequately supported by the health system, TBAs can successfully manage childhood pneumonia in villages at the lowest possible cost and with a high degree of community acceptance. TBAs and VHWs are the most suitable community-based health workers for ARI control programmes in developing countries. PMID- 7867136 TI - Poliomyelitis in Oman: acute flaccid paralysis surveillance leading to early detection and rapid response to a type 3 outbreak. AB - Countries are increasingly requesting guidance on carrying out acute flaccid paralysis (AFP) surveillance, aimed at detecting and confirming all cases of acute paralytic poliomyelitis. The experience of Oman provides many lessons in this respect. AFP surveillance in Oman was established systematically. First, an epidemiologist was assigned to coordinate surveillance, and a laboratory for performing polio-virus isolation was identified. Next, operational guidelines for AFP surveillance were developed and widely promoted among health staff. The quality of the system has been monitored for more than 3 years with selected performance indicators. From January 1990 to April 1993, 49 AFP cases were reported, corresponding to an average annual rate of 2.1 AFP cases per 100,000 children aged less than 15 years. A total of 98% of the AFP cases were investigated within 48 hours of being reported; two stool samples were obtained from 94% of the cases. Following complete investigation, nearly a third of the reported AFP cases were classified as being clinically compatible with Guillain Barre syndrome. Four AFP cases, all reported in 1991, were confirmed to be due to wild type 3 poliovirus. Because AFP surveillance detected these cases rapidly, Oman was able to carry out outbreak control measures promptly and more than 350,000 extra doses of oral poliovirus vaccine were delivered to children under 6 years of age. PMID- 7867137 TI - Poliomyelitis surveillance in Shandong Province, China, 1990-92. AB - In Shandong Province, China, programmes were initiated in 1991 for mass immunization against poliomyelitis and for the immediate reporting of acute flaccid paralysis (AFP). The incidence of non-poliomyelitis AFP was found to be 0.46-0.61 cases per 100,000 children per annum. It appeared that illness resembling the Guillain-Barre syndrome was underreported. The incidence of such illness peaked among children aged 2-3 years. Although laboratory investigations have improved, in 1992 they were still inadequate in nearly a third of confirmed poliomyelitis cases. As the prevalence of wild poliovirus declines in China, reliable laboratory support needs to be established and adequately sensitive and specific AFP surveillance be developed if poliomyelitis is to be eradicated. PMID- 7867138 TI - Malaria control and longitudinal changes in levels of DDT and its metabolites in human serum from KwaZulu. AB - Blood samples were obtained on four occasions over a 12-month period from individuals living in KwaZulu, South Africa, who had been exposed to DDT (1,1,1 trichloro-2,2-bis(4-chlorophenyl)ethane) as a consequence of its use in their homes to control transmission of malaria. The longitudinal changes in serum DDT and its major metabolities, DDE and DDD, were determined. No additional risk was considered to have been presented by the increases that occurred following application of the pesticide. There were significant increases in DDT, DDE and sigma DDT (DDT + its metabolites) for the age group > or = 21 years, but for the age group 3-20 years a reduction in serum levels occurred over 12 months. Two concurrent processes probably govern the increase and decrease in serum levels, and the relative contributions of each interchange as the individual becomes older. The results suggest that children in KwaZulu experience conditions that differ from those of their parents, as well as from those that affect children in developed countries. In consequence, it is desirable that risk assessments of vector control chemicals consider all sectors of a population. PMID- 7867139 TI - Daily versus alternate-day regimen of amphotericin B in the treatment of kala azar: a randomized comparison. AB - Using a randomized study, we compared a daily and an alternate-day regimen of amphotericin B for the treatment of kala-azar, with respect to efficacy, adverse reactions, cost-effectiveness, and tolerance. The study subjects were 80 kala azar patients, drawn from the first four decades of life and matched by age, sex, and parasite load. The patients were randomly allocated to treatment groups A and B (40 patients per group). Patients in group A received a daily regimen of amphotericin B, starting with an escalating dose of 0.05 mg/kg body weight per day until a daily dose of 1 mg/kg was reached; the latter dose was then given daily till a total dose of 20 mg/kg body weight had been administered. The patients in group B also started with an escalating dose of 0.05 mg/kg but when 1 mg/kg was reached the drug was given on alternate days. All 80 patients using the two treatment regimens were cured, no patient relapsed in either group in 6 months of follow-up, and their bone-marrow aspirates were free of amastigotes. Treatment of kala-azar patients with the daily regimen of amphotericin B at a dose 1 mg/kg body weight was as effective, not more toxic, equally well tolerated, and much more cost-effective than the alternate-day regimen and should be adopted for treatment of this condition. PMID- 7867140 TI - Evaluation of the alkaline haematin D-575 method for haemoglobin estimation in east Africa. AB - In many health facilities in east Africa, haemoglobin estimation is performed using visual colour comparison methods. Efforts to establish colorimetric methods face numerous constraints, including the unavailability of standards for quality control. In contrast, the alkaline haematin D-575 method for haemoglobin estimation is a colorimetric method that uses primary standards prepared from pure, crystalline chlorohaemin. There is no significant difference in the accuracy of the alkaline haematin D-575 method and that of the reference haemiglobincyanide method (P > 0.05), and the response of the alkaline haematin D 575 method is linear for serially diluted blood samples over the haemoglobin concentration range 19.6-3.3 g/dl (r = 0.994, y = 1.01 x - 0.3). The method has a precision of +/-0.3 g/dl (coefficient of variation = (1.8%) for whole blood, and is suitable for use with fixed-wavelength haemglobinometers (lambda = 565 nm) or with colorimeters at lambda = 580 nm. Stable quality control standards could be prepared at provincial, zonal, or reference laboratories and distributed regularly to outlying laboratories. PMID- 7867141 TI - Cancer deaths in India: is the model-based approach valid? AB - The model-based cancer mortality estimates for India (775,800) are nearly double the data-based estimates (433,000), and are higher than even the incidence estimates (612,300). The model-based approach is therefore, at least in the case of India, incorrect. Established practice is to use real data to validate theoretical models, not to reject the data if apparently the model does not fit. PMID- 7867142 TI - Clinical trials of improved oral rehydration salt formulations: a review. AB - Reviewed are all the published clinical trials of glycine-based oral rehydration salts (ORS), L-alanine-based ORS, L-glutamine-based ORS, maltodextrin-based ORS, and rice-based ORS, as well as the results of several recently completed, but unpublished, studies of these formulations that were supported by WHO. All experimental ORS formulations contained the same concentrations of salts as citrate-based WHO-ORS; all trials were randomized comparisons with WHO-ORS, and all except those with rice-based ORS were double-blind studies. The rate of stool loss and, less frequently, the duration of diarrhoea were used as indicators of clinical performance to compare ORS formulations. The following conclusions were reached concerning the efficacy and use of modified ORS formulations. Rice-based ORS (50 g/l) is superior to WHO-ORS for patients with cholera, and for such patients it can be recommended in any situation where its preparation and use are practical. Rice-based (50 g/l) and WHO-ORS solutions are equally effective for treating children with acute non-cholera diarrhoea, when feeding is resumed promptly following initial rehydration, as has been consistently recommended by WHO. Since rice-based ORS is not superior to WHO-ORS for such children, there is no apparent reason to advise a change from glucose to pre-cooked rice in the recommended formulation for WHO-ORS. Maltodextrin-based ORS formulations (50 g/l) and WHO-ORS appear to be equally effective for treating children with acute non cholera diarrhoea; there is no reason to advise a change from glucose to maltodextrin in the recommended formulation for WHO-ORS. Amino-acid-containing ORS formulations are not recommended for either non-cholera or cholera diarrhoea, since they are more costly and have no clinical advantage over WHO-ORS for children with acute non-cholera diarrhoea or over rice-based ORS for persons with cholera. PMID- 7867143 TI - Vaccination against typhoid fever: present status. AB - Typhoid fever remains an underestimated important health problem in many developing countries, causing more than 600,000 deaths annually in the world. Because of the reactogenicity of the parenteral, killed whole-cell vaccine, research has been oriented towards vaccination orally using live organisms and purified antigen. Live vaccine Ty21a, given by the oral route, has been extensively tested in several studies in developing countries. Its liquid formulation was the most effective, providing more than 60% protection after 7 years of follow-up. A Vi polysaccharide vaccine has been elaborated and provided more than 65% protection; after 3 years of follow-up the Vi antibody level was still at a high level. These two vaccines are therefore candidates for use in public health control programmes. Before such use, however, they need further evaluation for safety and protective efficacy when administered to the EPI targeted age groups. The question of whether typhoid fever vaccines interfere with the response to simultaneously administered measles vaccine must also be studied. New live vaccines, given by the oral route in one dose, have been constructed through genetic engineering. The first results are promising, but they must be improved before use in a large-scale study. These strains could be used as live vector to deliver foreign antigens to the intestinal mucosa. PMID- 7867144 TI - Interrupting the transmission of wild polioviruses with vaccines: immunological considerations. AB - In 1988 the World Health Assembly set the goal of global poliomyelitis eradication by the year 2000. Substantial progress has been made, and 143 countries reported no poliomyelitis cases associated with the wild virus in 1993. This article reviews the immunological considerations relevant to interrupting the transmission of wild polioviruses with vaccines. Although serum immunity prevents poliomyelitis in the individual, it is local immunity that is important in preventing the transmission of polioviruses in the community. Natural infection and vaccination with oral polioviruses vaccine (OPV) produce local immunity in the intestine and the nasopharynx in about 70-80% of individuals. In contrast, inactivated poliovirus vaccine (IPV) produces local intestinal immunity in only 20-30% of the individuals. With either vaccine, however, a substantial proportion of the immunized population can transmit the wild virus. Moreover, although serum immunity is long-lasting, limited data suggest that local immunity may not be as persistent. To interrupt the transmission of wild polioviruses efforts should be made to achieve and sustain high levels of poliovirus vaccine coverage. Recent outbreaks show that wild poliovirus poses a risk for unimmunized individuals, even when overall coverage levels are high. Delivery of poliovirus vaccine to hard-to-reach populations will be of increasing importance as countries progress toward the final stages of poliomyelitis eradication. The immunization status of persons from poliomyelitis-free countries should be updated prior to travel to poliomyelitis-endemic areas. PMID- 7867145 TI - Oral submucous fibrosis: etiology, pathogenesis, and future research. AB - Oral submucous fibrosis (OSMF), a precancerous condition of the oral cavity, has been studied by a number of workers in the field. The available epidemiological data showed a clear-cut geographical and ethnic predisposition, which suggested that certain customs/habits prevalent among the population groups in south-east Asia might be possible etiological factors. However, none of these customs was shown to be causally linked and the association in many cases was 'casual'. This led some workers to consider the importance of systemic predisposition, in addition to the effects of local factors on the oral mucosa. More research is needed to elucidate this problem. PMID- 7867146 TI - [Malaria situation in the People's Republic of China in 1993. Advisory Committee on Malaria, MOPH]. AB - According to case reporting from different provinces/autonomous regions/municipalities (P/A/M), the number of malaria cases amounted to 58,569 in the country (Taiwan not included) in 1993, the mean incidence being 4.982 per a hundred thousand, and the lethal cases due to malaria were 19. Among a total of 1.0862 billion population residing in areas where there were no reported malaria cases or the incidence was below 0.01%, 78.9 million in areas with an incidence of 0.10-1% and 10.6 million in areas with an incidence of 0.101-1% were detected. In Wanding City with a population of 10,000 on the border of Yunnan Province, high incidence of surpassing 1% was still revealed. The results of malaria surveillance in major endemic areas situated in 17 P/A/M with a coverage of 0.526 billion population indicated that 68,594 positive cases were detected from 12.423 million febrile patients undergone blood examination, showing a mean positive rate of 0.55%. 7,466 malaria parasite carriers were disclosed from target and migratory population in general examination, the mean parasite carrier rate being 1.26%. Because the province-based case reporting did not include migratory immigrants, and case missing was likely unavoidable during the reporting process at community level, the number of actual malaria cases was estimated to be no less than 100,000. 6,359 falciparum malaria cases (comprising mixed infections of Plasmodium falciparum and P. vivax) were detected in the whole country in 1993, accounting for 9.27% of the positive cases confirmed by blood examination; in addition three hundred and forty-four P. falciparum carriers were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867147 TI - [Immunological detection of organophosphate resistance of Culex mosquitoes using anti-esterase monoclonal antibody]. AB - Different strains of Culex mosquitoes (Cx. pipiens quinquefasciatus and Cx. Pipiens pallens) were immunologically-detected for organophosphate resistance with anti-esterase monoclonal antibody, and the results were compared with those detected by bioassay and biochemical microplate assay. It was found that the resistance-detection-rate detected by immunologic methods were higher than the corresponding data detected by the biochemical method, and the levels of resistance detected by sandwich-ELISA were higher than the corresponding levels detected by bioassay and the biochemical method. The thresholds for resistance in sandwich-ELISA were (at absorbence 450) > or = 0.5, and in microplate assay were (at absorbence 590) > or = 2.5 x 10(-3) mumol/min.mg protein. Dot-ELISA method was developed to meet the requirement of the field test and proved to be fast and convenient, especially in the detection of samples with higher esterase activity. PMID- 7867148 TI - [Amplification in vitro and identification of small subunit ribosomal DNA fragment of Plasmodium falciparum]. AB - According to computer analysis of SSUrDNA sequences of Plasmodium, other protozooa and human, two oligonucleotide primers were designed. A DNA fragment, about 570 base pairs, was successfully amplified by two temperature point polymerase chain reaction from the genomic DNA of cultivated erythrocytic stage of P. falciparum FCC/YN (Simao), but no fragment was obtained from that of P. vivax, L. donovani, T. gondii and humans. It has been confirmed that the amplified fragment was indeed expected SSUrDNA segment of P. falciparum by means of restriction endonuclease digestions and Northern blot hybridization. PMID- 7867149 TI - [Study on allele frequency in Oncomelania from the mainland of China]. AB - Nine populations of Oncomelania, field-collected from Anhui, Shanghai, Jiangsu, Zhejiang, Jiangxi, Hunan, Hubei, Sichuan and Yunnan were studied by horizontal starch gel electrophoretic method with 24 enzyme systems (AAT, AcPH, AK, AO, APH, CK, EST, GDH, GPI, G6PD, HBD, ISDH, LAP, LDH, ME, MDH, MPI, NADD, OCT, PGM, 6PGD, SDH, SOD, XDH) analyzed. 40 loci and 117 alleles were detected in the Oncomelania. Both of GPI and PGM-I, with 7 alleles, were the most variable loci. 22 loci had more than 3 alleles each. Of 40 loci examined in the 24 isozyme systems, 14 were found to be polymorphic, the proportion of multilocus enzymes being 58.3%. Our results showed that the genetic polymorphism existing in the populations of Oncomelania in the mainland of China. PGM and MDH, were found in both the populations of Oncomelania and strains of Schistosoma japonicum in the mainland of China. The results provided a new idea for studying snails and Schistosoma. Also, we found that there might be some correlation between the polymorphic locus and the feature of the shell of Oncomelania snail. PMID- 7867150 TI - [Pathological studies on alveolar hydatid in gerbils treated with albendazole and praziquantel]. AB - Pathological changes in alveolar hydatids from experimentally infected gerbils were studied after administration of albendazole or praziquantel. The animals were divided into several groups including the control one, and drugs of different dosages were given separately to different groups with diverse durations of infection. According to the microscopical observation, the hydatids could be categorized into 3 grades: grade I, degenerated cysts; grade II, stable cysts (showing no proliferation); grade III, proliferated cysts. Larger proportion of grade I cysts were found in the group treated with albendazole at high dosage (33.3%) and the two groups treated with praziquantel (25.0% and 16.3%). The proportion of grade I cysts in gerbils with shorter duration (45 d) of infection was larger than those with longer duration (60 d). Lymphocyte infiltration to various extent was present surrounding the alveolar hydatid cysts in all the treated groups. More marked infiltration of lymphocytes was observed in albendazole treated gerbils (106.9 +/- 34.3-300.1 +/- 59.5) (P < 0.001). However, the combined medication of albendazole and praziquantel was less efficacious. PMID- 7867151 TI - [Clinicopathological observations on 28 cases of cutaneous leishmaniasis in Karamay area]. AB - Clinicopathological observations on 28 cases of cutaneous leishmaniasis with dermal lesions for 1-48 months were carried out. The cutaneous lesions detected in the patients might be categorized into four types. 1. Papular eruption or plaque. It was predominated by inflammatory reaction, including numerous leishmanias and macrophages and other inflammatory cells infiltrating in cutaneous tissue. 2. Soft node or abscess. It was composed of necrotic tissues, many degenerated and dead leishmanias as well as disintegrated inflammatory cells in the focal site. 3. Ulceration. It contained necrotic cutaneous tissue, a considerable number of dead leishmanias and granuloma formation. 4. Hard nodule. Tissue proliferation and healing were distinct, which was indicated by the increase of fibroblasts and fibrous tissue formation, round cells infiltration as well as the foreign body giant cell appearance; besides, a few leishmanias existed; occasionally, scar formation was visible in the superficial and deep layers of the derma. The paper presented for the first time the histopathological changes of cutaneous leishmaniasis in China. And, the description of cutaneous lesions will be of significance in the differential diagnosis between cutaneous leishmaniasis and post kala-azar dermal leishmaniasis. PMID- 7867152 TI - [Comparative study on three serologic tests for detecting antibodies in cases with bancroftian microfilaremia]. AB - A comparative study was conducted for detecting antibody levels of bancroftian microfilaremia cases by using three serologic tests, IFAT, ELISA and dot-ELISA. A total of 102 serum specimens were collected from bancroftian microfilaremia cases. The positive rate was 89.2% (91/102) with IFAT (serum dilution > or = 1:20), 84.3% (86/102) with ELISA (OD value > or = 0.440) and 89.2% (91/102) with dot-ELISA (serum dilution > or = 1:80), respectively (P > 0.05); while in healthy individuals from non-endemic areas the false positive rate was 0(0/30), 1.8(1/55) and 0(0/54), respectively. The results indicated that there were no statistically significant differences among the three serologic tests. There was no correlation found in this study between microfilaria density and the antibody level. It was also proved that the detection rate of the combined use of either 2 or 3 tests was higher than each of the three tests; the positive rates being 94.1%-98.0%. PMID- 7867153 TI - [Experimental and clinical study on pneumocystosis. III. Development and characterization of monoclonal antibody against Pneumocystis carinii]. AB - BALB/c mice were repeatedly inoculated subcutaneously with purified rat source Pneumocystis carinii (P.c.) cysts. Six weeks later, the spleen cells were fused with NS1 myeloma cells, and a mouse hybridoma producing monoclonal antibody against P.c. was established and cloned, which was named as 4D7 McAb. Its mean of chromosome was 82. The 4D7 McAb was shown to be IgG1 subclass. It reacted mainly with 54 kDa polypeptide of P.c. in EITB. 4D7 McAb could clearly recognize P.c. by immunohistochemical staining in the specimens from confirmed Pneumocystis carinii pneumonia (PCP) patients, and the sensitivity and specificity were both 100% for diagnosis of PCP (11/11). No cross-reaction of 4D7 McAb was found with Pneumococcus, Candida albicans and Cryptococcus neoformans, as well as all examined normal human tissues. PMID- 7867154 TI - [Study on influence degree of probability of endemic factors for schistosomiasis transmission in Yunnan mountainous regions]. AB - In Zhonghe Village of Weishan County, Yunnan Province, a schistosomiasis endemic area of mountainous valley subtype, an epidemiological investigation was conducted on its natural, biological and social factors influencing schistosomiasis transmission in 1987-1990. The results were analyzed by stratified sampling analysis and probability accumulation method. It was demonstrated that 12 of 29 factors were the most important factors influencing schistosomiasis transmission including annual average air-temperature, number of infection sources, number of spots with infected snails, water temperature and annual average rainfall, etc. The values of influence degree before and after intervention measures were 3.513 and 2.066, respectively, the decrease being 41%. PMID- 7867155 TI - Schistosoma japonicum: size of egg granulomas in vaccinated and non-vaccinated hosts as observed in bovines. AB - The present paper reported the results of studies on the size of Schistosoma japonicum egg granulomas in susceptible and poorly susceptible, vaccinated and non-vaccinated, hosts as observed in bovines. It was noted that in both cattle and buffaloes, the mean size of the granuloma was smaller in vaccinated than in the non-vaccinated. The vaccinated bovines will accordingly not only be benefited by the reduction of the survival rate of the challenged schistosomula but also by decreasing the size of the egg granulomas. PMID- 7867156 TI - Effect of albendazole on the larvae and eggs of Necator americanus in golden hamster. AB - When golden hamsters infected with adult Necator americanus were treated ig with albendazole(Alb) 75 or 150 mg/kg, the efficacy rates were 83.8% and 100%, respectively. Three days before treatment, the mean numbers of larvae recorded from the incubation of feces from 2 treated groups were 29,716 +/- 3,299 and 28,256 +/- 118 per gram of feces, while in the control group, it was 8,828 +/- 2,659. Within 3 days after treatment, no larva was detected in the 2 treated groups, but in the control group the mean larva number was 9,066 +/- 7,416. Furthermore, in 2 treated groups none or only a few degenerated eggs could be found using saturated saline solution method. when infected golden hamsters were treated ig with Alb at a single dose of 150 or 300 mg/kg on day 3, 7 or 14 after infection with the third stage larvae, the egg positive rates in the feces were 0 9.1%, while the worm reduction rates were 96.8-100%. PMID- 7867157 TI - [Dynamic study on relationship between serum SEAIC level and hepatic pathological changes in mice infected with Schistosoma japonicum]. AB - Using purified rabbit polyclonal antibodies to SEA, avidin-biotin system and capture ELISA technique, we observed the dynamic changes in the level of the circulating soluble egg antigen-antibody complex (SEAIC) in murine sera at various weeks post infection. Simultaneously, the diameter and area of liver egg granuloma were measured by using profile analytical technique. Serum SEAIC was first detected 4 weeks post infection (p.i.), reaching peak level at 6-7th week, and then gradually dropped, and maintained at moderately high level till the end of the observation (12 weeks p.i.). Schistosome eggs appeared in liver tissue at 4 weeks p.i. No egg granuloma could be found until 6 weeks p.i. The peak of the average diameter and area of liver egg granuloma was noted at 7 weeks p.i., then dropped gradually. Its dynamic changes were consistent with that of the serum SEAIC level. It is therefore suggested that the serum SEAIC level could be a reference index reflecting the extent of the pathological changes of the liver. Moreover, SEAIC might play an important role in the pathogenesis of schistosomiasis japonica. PMID- 7867158 TI - [Studies on specific diagnostic antigen for filariasis]. AB - Soluble antigens of adult worms (MAA) and microfilariae (MFA) were analysed by means of SDS-PAGE and enzyme-linked immunoblotting (ELIB). The adult worms and microfilariae were collected from abdominal cavity of Mongolian jirds infected with Brugia malayi. The results indicated that MFA shared 64-67 kDa and 56-58 kDa protein components with the peritoneal fluid of the normal jirds. Sera from normal jirds were found to recognize 60 kDa, 74 kDa and 100 kDa fractions of MFA, but did not recognize any bands of MAA. Sera from positive jirds which were infected with B. malayi for 6 months could recognize 42 kDa and 14.5 kDa of MAA, but sera from negative jirds could not. The results indicated that the 42 kDa and 14.5 kDa protein components of MAA might be specific diagnostic antigen fractions. PMID- 7867159 TI - Effect of albendazole on Ancylostoma caninum larvae migrating in the muscles of mice. AB - When mice inoculated with 1,000 third-stage larvae of Ancylostoma caninum for 1 week were treated intragastrically (ig) with albendazole (Alb) 75, 150 or 300 mg/kg.d for 3 days, the mean larva numbers collected from the muscles of each group were 2.7 +/- 1.7, 2.0 +/- 1.5 and 1.0 +/- 1.0, respectively, being much less than that 205 +/- 68 of the control group. In mice treated ig with Alb 150 mg/kg.d for 3 days, the concentrations of Alb and its effective metabolite, albendazole sulfoxide (AlbSO), were determined in plasma and the muscles at different intervals after the last medication using high performance liquid chromatography. The results showed that only low concentrations of Alb were detected in both plasma and the muscles. However, higher concentrations of AlbSO were found not only in the plasma (5.4-10.5 micrograms/ml), but also in the muscles (2.2-4.6 micrograms/g). The higher contents of AlbSO in the muscles would be helpful for killing the Ancylostoma larvae migrating in the muscles of mice. PMID- 7867160 TI - [Comparative study on hemolytic toxicity of trifluoroacetoprimaquine and primaquine in rabbits]. AB - 5-trifluoroacetoprimaquine (M8506) exhibited high effect on tissue schizont of P. cynomolgi and low toxicity in mice, rats and dogs as compared with primaquine (PQ) according to our previous studies. In order to determine their hemolytic toxicity, we dosed rabbits with M8506 and PQ at a dose of 40 mg/kg per day for 4 days, respectively. Blood samples were drawn from the ear vein of the rabbits for determining of the following parameters, ie. methemoglobin (metHb), reticulocyte (ret) and Heinzbody (Hbd) on d0 before treatment and on d3, d5, d7, d10, d14 and d21 after treatment. The results showed that after drug administration the levels of metHb, ret and Hbd in PQ group increased on d3-d5, and reached their peak levels on d7-d10, and then declined gradually from d10-d14. The mean percentage concentration of metHb, mean count of ret and Hbd in PQ group on d7 after medication were 22.1 +/- 21.8%, 92.0 +/- 88.0/1,000 RBC and 203.8 +/- 126.7/1,000 RBC, which were significantly higher than those of the control (8.2 +/- 5.3%, 37.5 +/- 16.2/1,000 RBC and 57.4 +/- 45.1/1,000 RBC). In M8506 group, the mean Hbd count (196.3 +/- 123.1/1,000 RBC, on d7 after treatment was also higher than that of the controls, but its mean metHb percentage concentration (10.8 +/- 8.9%) and mean ret count (42.2 +/- 20.3/1,000 RBC) were similar to those of the controls (P > 0.05). The results suggested that the hemolytic toxicity induced by M8506 in rabbits might be similar to or even lower than that induced by PQ. PMID- 7867161 TI - [Relationship between the sex of Schistosoma japonicum and circulating antigen detection]. AB - Single sex cercariae were used to infect rabbits and the detection of circulating membrane antigen by dot-ELISA were followed up until 1 year postinfection. 9 rabbits infected with male cercariae (worm recovery 15-133, mean 53.1) and 9 rabbits infected with female cercariae (worm recovery 1-102, mean 39.1) were examined but no positive reaction was occurred. On the contrary, 7 rabbits infected with bi-sex cercariae (worm recovery 4-161, mean 67.1) all showed positive reactions 6-10 wks post-infection. Uni-sex female worms usually could not develop to maturity within rabbits even 1 year after infection, suggesting that the life-span of uni-sex female worm might be 1 year at least in rabbits. The uni-sex male worms could develop to maturity, being usually stout. The question why no circulating membrane antigen (even CCA, unpublished data) could be detected and the nature of antigen we detected needs further investigation. PMID- 7867162 TI - [Effect of trifluoroacetoprimaquine on erythrocytic schizonts of rodent malaria]. AB - Effect of trifluoroacetoprimaquine oxalate (M8506) and primaquine (PQ) on blood schizonts of Plasmodium berghei were determined using the method of 4-day suppressive test within extended observation period of 60 d. When mice infected with Plasmodium berghei ANKA strain were treated ig with M8506 or PQ at a same daily dose of 20 mg/kg for 4 d, the cure rates were 100% and 90%, respectively. The two drugs also showed prominent suppressive effects on chloroquine-resistant P. berghei NS line and pyronarine-resistant P. berghei RP line, but the parasitemia still remained positive or all of the mice treated recrudesced, indicating the existence of cross resistance between trifluoroacetoprimaquine and other erythrocytic schizonticides, including chloroquine and pyronaridine. PMID- 7867163 TI - [Observation on a new sensillum of cerci of Periplaneta americana by scanning electron microscopy]. AB - This paper deals with the morphology of the cerci of Periplaneta americana under the scanning electron microscope. In this initial study a new sensillum on the ventral surface of cercus segments is found and described in detail. This sensillum has an upside-down disc-shaped base with a central slender spear-shaped receptor hair, hence the authors named it "speared sensillum". PMID- 7867164 TI - [Present status and prospect in the diagnosis of Schistosomiasis japonica in China]. PMID- 7867166 TI - As Congress forges new directions, AHA must make its voice heard. PMID- 7867165 TI - New genetic approaches. Establishing resources for research. PMID- 7867167 TI - Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. AB - BACKGROUND: Experimental evidence suggests that flow-dependent dilatation of conduit arteries is mediated by nitric oxide (NO) and/or prostacyclin. The present study was designed to assess whether NO or prostacyclin also contributes to flow-dependent dilatation of conduit arteries in humans. METHODS AND RESULTS: Radial artery internal diameter (ID) was measured continuously in 16 healthy volunteers (age, 24 +/- 1 years) with a transcutaneous A-mode echo-tracking system coupled to a Doppler device for the measurement of radial blood flow. In 8 subjects, a catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of the NO synthase inhibitor NG-monomethyl-L arginine (L-NMMA; 8 mumol/min for 7 minutes; infusion rate, 0.8 mL/min). Flow dependent dilatation was evaluated before and after L-NMMA or aspirin as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3-minute cuff wrist occlusion). Under control conditions, release of the occlusion induced a marked increase in radial blood flow (from 24 +/- 3 to 73 +/- 11 mL/min; P < .01) followed by a delayed increase in radial diameter (flow mediated dilatation; from 2.67 +/- 0.10 to 2.77 +/- 0.12 mm; P < .01) without any change in heart rate or arterial pressure. L-NMMA decreased basal forearm blood flow (from 24 +/- 3 to 13 +/- 3 mL/min; P < .05) without affecting basal radial artery diameter, heart rate, or arterial pressure, whereas aspirin (1 g PO) was without any hemodynamic effect. In the presence of L-NMMA, the peak flow response during hyperemia was not affected (76 +/- 12 mL/min), but the duration of the hyperemic response was markedly reduced, and the flow-dependent dilatation of the radial artery was abolished and converted to a vasoconstriction (from 2.62 +/- 0.11 to 2.55 +/- 0.11 mm; P < .01). In contrast, aspirin did not affect the hyperemic response nor the flow-dependent dilatation of the radial artery. CONCLUSIONS: The present investigation demonstrates that NO, but not prostacyclin, is essential for flow-mediated dilatation of large human arteries. Hence, this response can be used as a test for the L-arginine/NO pathway in clinical studies. PMID- 7867168 TI - Late lumen loss after coronary angioplasty is associated with the activation status of circulating phagocytes before treatment. AB - BACKGROUND: The purpose of this pilot study was to identify biological risk factors for restenosis after percutaneous transluminal coronary angioplasty (PTCA) to predict the long-term outcome of PTCA before treatment. METHODS AND RESULTS: To investigate whether blood granulocytes and monocytes could determine luminal renarrowing after PTCA, several characteristics of these phagocytes were assessed before angioplasty in 32 patients who underwent PTCA of one coronary artery and who had repeat angiograms at 6-month follow-up. The plasma levels of interleukin (IL)-1 beta, tumor necrosis factor-alpha, IL-6, fibrinogen, C reactive protein, and lipoprotein(a) before angioplasty were assessed as well. We found that the expression of the membrane antigens CD64, CD66, and CD67 by granulocytes was inversely associated with the luminal renarrowing normalized for vessel size (relative loss) at 6 months after PTCA, while the production of IL-1 beta by stimulated monocytes was positively associated with the relative loss. Next, these univariate predictors were corrected for the established clinical risk factors of dilation of the left anterior descending coronary artery and current smoking, which were statistically significant classic predictors in our patient group. Only the expression of CD67 did not predict late lumen loss independent of these established clinical risk factors. Multiple linear regression analysis showed that luminal renarrowing could be predicted reliably (R2 = .65; P < .0001) in this patient group on the basis of the vessel dilated and only two biological risk factors that reflect the activation status of blood phagocytes, ie, the expression of CD66 by granulocytes and the production of IL-1 beta by stimulated monocytes. CONCLUSIONS: The results of the present study indicate that activated blood granulocytes prevent luminal renarrowing after PTCA, while activated blood monocytes promote late lumen loss. To validate this new finding, further study in an independent patient group is required. PMID- 7867169 TI - Genetic heterogeneity of heart-hand syndromes. AB - BACKGROUND: Heart-hand syndromes compose a class of combined congenital cardiac and limb deformities. The proto-typical heart-hand disorder is Holt-Oram syndrome, which is characterized by cardiac septation defects and radial ray limb deformity. We have recently mapped the Holt-Oram syndrome gene defect to the long arm of human chromosome 12 in two families. The role of this disease locus in the pathogenesis of related conditions such as heart-hand syndrome type III (cardiac conduction disease accompanied by skeletal malformations) or familial atrial septal defects is unknown. METHODS AND RESULTS: Clinical evaluations and genetic linkage analyses were performed in five additional kindreds with Holt-Oram syndrome and also in one kindred with heart-hand syndrome type III and one kindred with familial atrial septal defect and conduction disease. Holt-Oram syndrome in all five kindreds mapped to chromosome 12q2. These studies and previous data provide odds of greater than 10(25):1 that the Holt-Oram syndrome disease gene is at chromosome 12q2. In contrast, neither the phenotypically similar disorder heart-hand syndrome type III nor the locus responsible for a familial atrial septal defect with atrioventricular block maps to chromosome 12q2. CONCLUSIONS: We demonstrate that heart-hand syndromes are genetically heterogeneous. Conditions that clinically appear to be partial phenocopies of Holt-Oram syndrome arise from distinct disease genes. PMID- 7867170 TI - Antithrombotic effects of thrombolytic agents in a platelet-rich femoral vein thrombosis model in the hamster. AB - BACKGROUND: The extent and mechanism of the antithrombotic properties of fibrin selective and non-fibrin-selective thrombolytic agents have not yet been established. METHODS AND RESULTS: The antithrombotic, thrombolytic, fibrinogenolytic, and pharmacokinetic properties of the following substances were determined in hamsters in the absence of conjunctive anticoagulant or antiplatelet therapy: recombinant tissue-type plasminogen activator (rTPA), recombinant single-chain urokinase-type plasminogen activator (rscu-PA), two chain urokinase-type plasminogen activator (UK), with a rTPA deletion mutant lacking amino acids 6 to 173 and a mutation N184E (K2Pt), a rTPA/rscu-PA chimeric plasminogen activator consisting of amino acids 1 to 3 and 87 to 274 of rTPA and amino acids 138 to 411 of rscu-PA (K1K2Pu), streptokinase (SK), and recombinant staphylokinase (STAR). The anti-thrombotic effect, defined as the intravenous dose required to reduce mural thrombus formation to 50% in a platelet-mediated femoral vein thrombosis model in the hamster, was 6 +/- 1, 5 +/- 2, 1 +/- 0.05, 2.5 +/- 0.2, 0.02 +/- 0.002, 1 +/- 0.09, and 2 +/- 0.3 mg/kg (mean +/- SEM), respectively. The amounts, given as intravenous infusion over 60 minutes that induced 50% clot lysis in a hamster pulmonary embolism model, were 0.18 +/- 0.03, 1.1 +/- 0.05, 0.9 +/- 0.13, 0.34 +/- 0.03, 0.04 +/- 0.003, 0.05 +/- 0.005, and 0.04 +/- 0.001 mg/kg, respectively, indicating that for most thrombolytic agents the antithrombotic dose is much higher than their thrombolytic dose. The fibrinogen levels, measured 40 minutes after bolus injection, were reduced to 50% of baseline with 3.1 +/- 0.2, 2.5 +/- 0.3, 1.2 +/- 0.08, 2.0 +/- 0.14, 1.7 +/- 0.65, 0.54 +/- 0.03, and 1.2 +/- 0.11 mg/kg, respectively. Mean residence times following intravenous bolus injection were: 18 +/- 1, 14 +/- 1, 100 +/- 10, 80 +/ 2, 20 +/- 3, and 34 +/- 5 minutes for rTPA, rscu-PA, K2Pt, K1K2Pu, SK, and STAR, respectively. Regression analysis revealed a significant correlation of the antithrombotic effect with the fibrinogen breakdown (P = .006) but not with the thrombolytic potency or with the mean residence time. CONCLUSIONS: These observations support the hypothesis that thrombolytic therapy with fibrinogen sparing agents requires the conjunctive use of anticoagulant and/or antiplatelet agents. PMID- 7867171 TI - Circadian variation in the efficacy of tissue-type plasminogen activator. AB - BACKGROUND: The frequency of onset of acute myocardial infarction follows a circadian pattern, with a peak incidence between 6:00 AM and noon. Circadian variations have been defined for platelet aggregation, plasminogen-activator inhibitor, and a number of hemostatic and physiological factors, all of which might predispose toward clotting in the late morning and thrombolysis in the evening. Thus, the hypothesis for this retrospective analysis was that tissue type plasminogen activator (TPA) has greater efficacy when administered between noon and midnight, as measured by coronary patency 90 minutes after initiation of treatment. METHODS AND RESULTS: Seven hundred twenty-eight patients were enrolled in either of two studies in which TPA was administered under a uniform protocol for the treatment of acute myocardial infarction. Of these, 692 patients had qualifying arteriograms that allowed standardized assessment by a core angiographic laboratory of the primary end point of 90-minute patency. TPA has a circadian pattern of efficacy, with greater TIMI grade 3 patency when administered between noon and midnight (P < .001). When TPA was given within 2 hours of symptoms (n = 127), the total patency was highest and there was a trend (P = .055) toward the greatest magnitude difference occurring between AM and PM patency. The onset of myocardial infarction was confirmed to have a marked circadian variation with a peak incidence about 10:00 AM. The peak efficacy of TPA was about 8:00 PM, representing a phase difference of about 10 hours after peak infarction incidence. CONCLUSIONS: There is a circadian variation in the ability of TPA to rapidly open coronary arteries, with highest efficacy between noon and midnight. This complements clinical and in vitro knowledge of increased morning thrombosis and is concordant with knowledge of increased morning thrombosis and is concordant with knowledge of a fibrinolytic profile that is more favorable for evening lysis. This finding has implications for understanding the circadian pathophysiology of myocardial infarction and for its chronotherapy. PMID- 7867172 TI - Noninvasive determination of infarct artery patency by cine magnetic resonance angiography. AB - BACKGROUND: In survivors of myocardial infarction, restoration of antegrade flow in the infarct artery reduces morbidity and mortality. At present, coronary artery patency must be assessed invasively with contrast angiography. A noninvasive method of evaluating infarct artery patency would be useful in managing survivors of infarction. This study was performed to determine whether magnetic resonance (MR) imaging could reliably assess infarct artery patency in this patient population. METHODS AND RESULTS: Eighteen survivors of myocardial infarction (11 men and 7 women, aged 35 to 74 years) who were consecutively referred for cardiac catheterization underwent contrast coronary angiography and cine MR coronary angiography. Sequential overlapping images of the infarct artery were acquired with cine MR during 15- to 20-second periods of breath-holding. In each study, proximal, middle, and distal segments of infarct arteries were classified as having antegrade, collateral, or no flow. The infarct artery was the left anterior descending in 10 patients, the right anterior descending in 7, and the circumflex in 1. When compared with the results of contrast angiography, MR imaging correctly identified the presence or absence of antegrade flow in the infarct artery of all 18 patients. In addition, cine MR coronary angiography with presaturating pulses correctly established the presence or absence of collateral filling of the distal portion of occluded arteries in 6 of 7 subjects. CONCLUSIONS: In survivors of myocardial infarction, cine MR coronary angiography can reliably determine the patency and direction of flow in the infarct artery. PMID- 7867173 TI - Comparative real-time effects on platelet adhesion and aggregation under flowing conditions of in vivo aspirin, heparin, and monoclonal antibody fragment against glycoprotein IIb-IIIa. AB - BACKGROUND: A real-time in vitro system of human platelet thrombosis under arterylike flowing conditions similar to those produced in vivo by angioplasty would be useful for the evaluation of potential antiarterial thrombotic agents in association with in vivo trials. Aspirin, heparin, and the chimeric monoclonal antibody antigen-binding fragment 7E3 (c7E3 Fab) directed against platelet glycoprotein (GP) IIb-IIIa have been used in attempts to delay or prevent thrombotic reocclusion of coronary arteries after angioplasty. We compared the effects of these agents administered in vivo on GPIb-mediated platelet adhesion to von Willebrand factor (vWF)/collagen type I (as in atherosclerotic subendothelium) and on subsequent GPIIb-IIIa-fibrinogen/vWF-mediated platelet aggregation under flowing conditions analogous to those in constricted coronary arteries. METHODS AND RESULTS: Citrated whole blood containing mepacrine-labeled platelets from patients and healthy donors was perfused for 1 minute at an abnormally elevated shear rate of 1500 seconds-1 (arterial wall shear stress of 50 to 60 dynes/cm2) at 37 degrees C over collagen I/vWF. The number of adherent fluorescent platelets was quantified every 15 seconds with a low-light-level video camera and epifluorescent microscopy. After 5 healthy donors had ingested 975 mg aspirin, platelet adhesion was unaffected in the aspirin-treated blood compared with the control blood in all experiments (10 of 10), and subsequent aggregation was unchanged in most runs (8 of 10). The blood of 3 aspirin-treated patients undergoing angioplasty was analyzed before and after a 12,000-U heparin injection and 2 minutes, 2 hours, and 24 hours after infusion of 0.25 mg/kg of c7E3 Fab. In these patients, the bolus of heparin did not inhibit either platelet adhesion to collagen I/vWF or subsequent aggregation. In contrast, there was > 50% inhibition of platelet aggregation 2 minutes after the infusion of c7E3 Fab in all 3 patients, and inhibition persisted in 2 of the 3 patients at 2 hours and 24 hours after c7E3 Fab. CONCLUSIONS: In contrast to aspirin or heparin, the in vivo injection of c7E3 Fab considerably reduces platelet aggregate formation mediated by the binding of fibrinogen, vWF, or some other ligand to platelet GPIIb-IIIa under conditions of abnormally increased shear stress analogous to those in narrowed coronary arteries. Platelet adherence to collagen I/vWF is not affected. This study describes an in vitro model of arterial injury (similar to angioplasty) that uses human blood to compare directly, in real time, the precise relative effects of aspirin, heparin, and c7E3 Fab on platelet adhesion and subsequent aggregation. PMID- 7867174 TI - Coronary calcium, as determined by electron beam computed tomography, and coronary disease on arteriogram. Effect of patient's sex on diagnosis. AB - BACKGROUND: Coronary artery calcium identified by electron beam computed tomography (EBCT) has potential for noninvasive localization of coronary atherosclerotic disease. However, the effect of a patient's sex on its diagnostic capability has not been examined in a clinical population. METHODS AND RESULTS: Fifty women and 89 men had EBCT scans done an average of 1 day after coronary arteriography. Maximum arteriographic percent luminal diameter stenosis of any artery was paired with the total EBCT coronary calcium score for each subject. The women (age, 56 +/- 11 years [mean +/- SD]) were older than the men (age, 47 +/- 7 years), but the subjects were matched for indications for arteriography and extent of disease as assessed by arteriography. Sensitivity, specificity, and positive and negative predictive values for coronary calcium were nearly identical for men and women, regardless of the degree of arteriographic disease. EBCT was highly sensitive to the presence of arteriographic disease (range, 94% to 100%), but had only moderate specificity (57% to 66%) for significant disease (> or = 50% stenosis) and low specificity (35% to 38%) for any arteriographic disease (> 0% stenosis). Negative predictive values in men and women ranged from 79% to 91% for any arteriographic disease and from 95% to 100% for significant disease, respectively. Numerical calcium scores were significantly different between subjects with normal arteriograms and those with significant disease; however, calcium score had limited power to separate trivial, moderate, and significant disease. Receiver operating characteristic curve areas, determined as an extension of the analyses of sensitivity and specificity, were high for EBCT defined calcium scores for both any arteriographic disease and significant arteriographic disease, and were not different between the sexes. CONCLUSIONS: In a middle-aged population, noninvasive definition of coronary calcium by EBCT has similar predictive value for arteriographic coronary artery disease in men and women. PMID- 7867175 TI - Intermittent transdermal nitroglycerin therapy in angina pectoris. Clinically effective without tolerance or rebound. Minitran Efficacy Study Group. AB - BACKGROUND: The objectives of this study were to assess the antianginal and anti ischemic effects of three dose levels of transdermal nitroglycerin patches applied for 12 hours daily for 30 days. The study also assessed the development of tolerance and rebound. Intermittent transdermal nitroglycerin therapy with a patch-free period of 10 to 12 hours each day has documented clinical benefits during the period of patch application, but studies have failed to clearly document prolonged exercise duration for the entire period of patch application. This study was designed to evaluate the efficacy and duration of action of a range of doses of nitroglycerin. The study also permitted the assessment of the maintenance of initial effects, the development of tolerance, and the presence of rebound. METHODS AND RESULTS: This study was a multicenter, randomized, double blind, placebo-controlled parallel design trial with treadmill exercise tests at days 0, 1, 7, 15, and 30. Tests were carried out up to 12 hours after patch application. There was a statistically significant treatment effect with increases in treadmill walking time to moderate angina in each nitroglycerin patch group compared with placebo at various time points up to 12 hours throughout the 30-day study period. Secondary efficacy parameters, including the consistent increase in time to 1-mm ST-segment depression, supported the primary efficacy results. There was no evidence of tolerance or rebound. CONCLUSIONS: Intermittent transdermal nitroglycerin therapy increases exercise duration and maintains anti-ischemic effects for 12 hours after patch application, throughout 30 days of therapy, without significant evidence of nitrate tolerance or rebound phenomena. PMID- 7867176 TI - Increased prevalence of coronary ectasia in heterozygous familial hypercholesterolemia. AB - BACKGROUND: Although coronary atherosclerosis most commonly produces clinical effects as a result of stenosis, aneurysmal disease also occurs. We have found an increased prevalence of ectasia and aneurysmal disease in familial hypercholesterolemia (FH) suggesting a link between plasma lipoproteins and coronary aneurysms. METHODS AND RESULTS: In 197 asymptomatic subjects with FH, we examined the prevalence of ectasia and its association with coronary risk factors. An ectatic segment was defined as one with a luminal diameter > 1.5 times that of the adjacent normal segment, excluding poststenotic dilation. Among subjects with FH, 15% had ectasia compared with 2.5% of an age- and sex-matched control group of 198 subjects without FH presenting for coronary angiography (P < .001). These control patients had significantly more severe coronary atherosclerosis than patients with FH. Ectasia was 3 times more common in men than women (P < .025). Neither age nor hypertension was predictive. Although in part reflecting the striking sex differential, ectasia was strongly associated with a lower HDL cholesterol level (P = .003), a higher LDL/HDL ratio (P = .003), and to a lesser extent, a higher LDL cholesterol level (P = .07). No association was found with plasma triglycerides or very low-density lipoprotein cholesterol levels. Among FH patients, ectasia was strongly associated with an overall index of occlusive atherosclerotic disease, based on quantitative angiography (P = .004). Intracoronary ultrasound interrogation of aneurysmal segments revealed circumferential intimal thickening. CONCLUSIONS: Coronary ectasia is more prevalent in patients with FH than in other patients with coronary atherosclerosis and shows a strong inverse association with HDL cholesterol levels. This suggests that disordered lipoprotein metabolism in FH may predispose patients to aneurysmal coronary artery disease. PMID- 7867177 TI - Redistribution of myocardial blood flow with topical nitroglycerin in patients with coronary artery disease. AB - BACKGROUND: Unlike nonselective coronary vasodilators, nitroglycerin (GTN) is said to exert its primary vasodilatory effect on epicardial conductance vessels. Thus, in experimental models of coronary occlusion GTN appears to preferentially direct blood flow to poststenotic zones of ischemia. This phenomenon has, to date, not been tested in humans. Using positron emission tomography we examined the effect of transdermal GTN on global and regional myocardial perfusion in patients with angiographically proven coronary artery disease. METHODS AND RESULTS: Myocardial perfusion with [13N]ammonia was estimated from dynamic time activity curves at baseline and 3 hours following application of either a 0.4 mg/h GTN skin patch (n = 10) or a placebo patch (n = 10) in a double-blind parallel design. From resliced cross-sectional images, regional flow, expressed as [13N]ammonia retention, was estimated from 216 myocardial sectors. Ischemia was defined as a significant reduction (> 2 SDs from average counts/pixel in maximally perfused zones) in [13N]ammonia retention within 10 contiguous myocardial sectors coupled with an increase or no change in counts derived from [18F]fluorodeoxyglucose. There was no change in global myocardial blood flow as expressed by [13N]ammonia retention following either placebo (0.61 +/- 0.14 to 0.62 +/- 0.12 min-1) or GTN (0.75 +/- 0.22 to 0.74 +/- 0.19 min-1). Conversely, there was a significant increase in the proportion of blood flow to the ischemic zones with GTN (73.9 +/- 12.6% to 94.9 +/- 17.8%; P < .05). No change in the distribution of blood flow to either ischemic or nonischemic zones was observed with placebo. A slight but insignificant decrease in [13N]ammonia retention in nonischemic zones was observed with GTN (1.01 +/- 0.31 to 0.93 +/- 0.26 min-1). CONCLUSIONS: This study suggests that under resting conditions topical GTN alters myocardial perfusion by preferentially increasing flow to areas of reduced perfusion with little or no change in global myocardial perfusion in patients whose angina is responsive to GTN. PMID- 7867178 TI - Angioscopic prediction of successful dilatation and of restenosis in percutaneous transluminal coronary angioplasty. Significance of yellow plaque. AB - BACKGROUND: Coronary angiography has been used to assess the anatomy of coronary artery and intraluminal pathological changes. However, it has several limitations in its diagnostic quality and sensitivity in the detection of intraluminal details. Angioscopy has enabled coronary artery lumens to be visualized directly and fine intraluminal morphological changes to be detected. The information obtained by angioscopy is expected to provide new insights into the mechanisms and pathophysiology of transluminal coronary angioplasty. METHODS AND RESULTS: Forty-seven patients (39 men and 8 women) with stable angina were enrolled in the present study. Angioscopy was performed before and after angioplasty with a 0.68 mm angioscope with a double-guiding catheter system. The patients who were successfully evaluated by angioscopy were divided into two groups according to the color of the lesion: group 1, mainly yellow; and group 2, white. Angiographic, angioscopic, and clinical parameters in the two groups were compared. Detailed angioscopic findings were obtained in 36 of the 47 patients (77%) before percutaneous transluminal coronary angioplasty (PTCA) and in 24 of the 47 (51%) after PTCA. Yellow plaque were found in 13 of 36 (36%). Age, sex, presence of coronary risk factors, serum cholesterol level, and duration of angina showed no correlation with plaque color. The incidence rates of dissection and thrombi after angioplasty also were not different. Successful dilatation was achieved in 13 of 13 patients (100%) in group 1 and in 21 of 23 (91%) in group 2. The restenosis rate of group 1 was significantly lower than that in group 2 (16.7% versus 57.9%, P < .05). Cox proportional hazards model revealed that plaque color was the independent variable associated with restenosis after PTCA (P = .03). CONCLUSIONS: The restenosis rate after successful balloon angioplasty differs, with the color of the target lesion being significantly higher in patients with solely white plaque. Therefore, angioscopic findings are highly predictive of restenosis. PMID- 7867179 TI - Coronary stenting decreases restenosis in lesions with early loss in luminal diameter 24 hours after successful PTCA. AB - BACKGROUND: Early loss of minimal luminal diameter (MLD) after successful percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher incidence of late restenosis. METHODS AND RESULTS: Sixty-six patients (66 lesions) with > 0.3 mm MLD loss at 24-hour on-line quantitative coronary angiography were randomized into two groups: 1, Gianturco-Roubin stent (n = 33) and 2, Control, who received medical therapy only (n = 33). All lesions were suitable for stenting. Baseline demographic, clinical, and angiographic characteristics were similar in the two groups. Restenosis (> or = 50% stenosis) for the overall group occurred in 32 of 66 patients (48.4%) at 3.6 +/- 1-month follow-up angiography. Restenosis was significantly greater in group 2 than in group 1 (75.7% versus 21.2%, P < .001). Vascular complications (21.2% versus 0%) and length of hospital stay (7.3 +/- 1 versus 2.4 +/- 0.5 days, P < .01) were higher for the stent group. Although at follow-up there were no differences in mortality or incidence of acute myocardial infarction between the two groups, patients in the control group had a higher incidence of repeat revascularization procedures (73% versus 21%, P < .001). CONCLUSIONS: In patients with successful PTCA but reduced luminal diameter demonstrated by repeat angiography at 24 hours, the Gianturco-Roubin stent appears to reduce angiographic restenosis at follow up. PMID- 7867180 TI - Elevated serum lipoprotein(a) is a risk factor for clinical recurrence after coronary balloon angioplasty. AB - BACKGROUND: Elevated lipoprotein (Lp) (a) concentrations are associated with coronary artery disease and myocardial infarction. Lp(a) is structurally related to proteins involved in lipid transport, fibrinolysis, coagulation, and cellular mitogenesis and is known to have important physiological interactions with the coagulation and fibrinolytic systems. Because these processes may be important to arterial healing after balloon injury, we hypothesized that elevated Lp(a) concentrations may be associated with recurrence of symptoms and restenosis after balloon angioplasty. METHODS AND RESULTS: We assessed 240 consecutive patients undergoing coronary balloon angioplasty with measurements of Lp(a), total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein A-I, and apolipoprotein B-100 concentrations from fresh specimens. Patients were evaluated 4 to 6 months after angioplasty for clinical recurrence by repeat angiography if angina had returned or by maximal exercise treadmill testing with thallium imaging if patients remained asymptomatic. Ninety-seven patients (40%) had clinical recurrence; 143 (60%) did not. Patients with recurrence had significantly greater Lp(a) concentrations compared with those without (median, 29 versus 14; P < .0001). Each patient quintile stratified by increasing Lp(a) concentrations had incrementally greater recurrence rates ranging from 27% (lowest quintile) to 60% (highest quintile). By multivariate logistic regression analysis, Lp(a) concentration was the only predictor of recurrence (P < .0001). A subset of frozen, stored serum samples showed a significant decrease in measured Lp(a) concentration over time (mean, 605 days; P < .01). CONCLUSIONS: An elevated Lp(a) concentration was a risk factor for clinical recurrence after percutaneous transluminal balloon coronary angioplasty. Other lipid levels or clinical characteristics were not significantly associated with recurrence. When serum was frozen and stored for a prolonged period, Lp(a) concentration decreased over time. PMID- 7867181 TI - Restenosis after delayed coronary angioplasty of the culprit vessel in patients with a recent myocardial infarction treated by thrombolysis. AB - BACKGROUND: Clinical follow-up after percutaneous transluminal coronary angioplasty (PTCA) of an infarct-related lesion has demonstrated a low incidence of recurrent symptoms and repeated revascularization. In the absence of systematic angiographic follow-up, this low rate of clinical restenosis may reflect either a truly lower incidence of anatomic restenosis or the lack of recurrent symptoms in patients with extensive infarction in the territory of the restenotic vessel. METHODS AND RESULTS: We studied 300 consecutive patients who, after a thrombolysis for myocardial infarction, underwent delayed (10.5 +/- 6 days after the myocardial infarction) PTCA of the infarct-related lesion. Procedural success was obtained in 253 patients (84%), and angiographic follow-up was performed in 205 of this group (81%) at a mean of 7.3 +/- 1.9 months. Restenosis (defined as the recurrence of > 50% stenosis) was present in 105 patients (51%). Only 34 of the 105 patients (32%) with angiographic restenosis were symptomatic; the other 68% had clinically silent restenosis. Of these 105 patients, 27 (13% of the total population undergoing follow-up angiography) had reocclusion at the dilated site at follow-up. The severity of the stenosis at follow-up and the late loss in minimal lumen diameter followed a nearly Gaussian distribution if the lesions that were totally occluded at follow-up were excluded. By multivariate analysis, two independent predictors of reocclusion were identified: a small reference diameter (P < .0005) and the presence of collateral vessels before the procedure (P < .01). Only one factor was associated with restenosis in the 178 patients who did not have reocclusion at follow-up; a Thrombolysis in Myocardial Infarction grade < or = 2 before the procedure (P < .0001). At follow-up, there was a significantly (P < .01) higher ejection fraction in patients without restenosis (56.1 +/- 13.4%) and in patients with restenosis without total occlusion (56.0 +/- 13.8%) than in patients with reocclusion (46.4 +/- 13.0%). CONCLUSIONS: Despite a satisfactory clinical outcome, delayed PTCA of an infarct-related lesion is associated with a high rate of angiographic recurrence. Two distinct mechanisms account for recurrent stenosis: progressive luminal renarrowing as documented after angioplasty of stable lesions and reocclusion of the infarct-related lesion. Only reocclusion is associated with a deterioration in left ventricular function at follow-up. PMID- 7867182 TI - Improvement of subendocardial myocardial perfusion after percutaneous transluminal coronary angioplasty. A myocardial contrast echocardiography study with correlation between myocardial contrast reserve and Doppler coronary reserve. AB - BACKGROUND: After angioplasty coronary reserve improves but does not normalize in most patients. The purpose of this study was to examine before and after angioplasty coronary reserve and transmural myocardial blood flow distribution using myocardial contrast echocardiography. METHODS AND RESULTS: Twelve patients with left anterior descending coronary artery stenosis were investigated before and immediately after angioplasty. A Doppler catheter was placed in the proximal segment. Myocardial contrast echocardiography was performed by imaging the septum in M mode in a parasternal view using a 3.0-mL bolus of sonicated amidotrizoate sodium meglumine through the guiding catheter. The gray level before injection was subtracted from the gray level after injection to maximize contrast time intensity curves. The area under the curve was used as an indicator of myocardial blood flow, and subendocardial/subepicardial ratios were measured. After baseline measurements were obtained, Doppler and echographic data were recorded after a bolus infusion of papaverine into the left main coronary artery. The same protocol was performed in patients after angioplasty and in five control subjects with normal coronary arteries. Before angioplasty, echocardiographic and Doppler coronary reserve were 2.57 +/- 0.48 and 2.54 +/- 0.57, respectively. Both increased after angioplasty to 3.65 +/- 0.57 and 3.36 +/- 0.70, respectively (P < .05). Coronary reserve values obtained in patients with these two methods under the different conditions and in control subjects were correlated (r = .81; P = .0001). Before angioplasty, subendocardial/subepicardial septal ratios decreased from 0.80 +/- 0.48 to 0.60 +/- 0.27 after papaverine (P < .05). However, after angioplasty, these ratios tended to increase, from 0.72 +/- 0.27 to 0.92 +/- 0.45 after papaverine, but they did not change in control subjects (1.11 +/- 0.23 to 0.92 +/- 0.11). CONCLUSIONS: These results show that myocardial contrast echocardiography yields flow reserve values that correlate with values obtained using intracoronary Doppler. This technique may be considered as an accurate tool to assess coronary reserve in humans. PMID- 7867183 TI - Shear-induced platelet aggregation is inhibited by in vivo infusion of an anti glycoprotein IIb/IIIa antibody fragment, c7E3 Fab, in patients undergoing coronary angioplasty. AB - BACKGROUND: Elevated levels of shear stress such as those that occur in stenotic arterial vessels can directly activate and aggregate platelets and thus contribute to the pathogenesis of acute arterial thrombosis. This shear-induced platelet aggregation (SIPA) is mediated by von Willebrand factor binding to platelet membrane glycoprotein (GP) Ib and GPIIb/IIIa. The chimeric Fab fragment of the monoclonal antibody 7E3 (c7E3 Fab) that binds selectively to GPIIb/IIIa is under clinical evaluation in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). This study was undertaken to investigate the effects on ex vivo SIPA of c7E3 Fab administered to patients undergoing PTCA. METHODS AND RESULTS: Six patients received aspirin (325 mg) and boluses of heparin (12,00o U) followed by c7E3 Fab 0.25 mg/kg. Blood collected from each patient before and after heparin treatment and at various time points after c7E3 Fab administration was subjected to laminar shear stress in a cone-and-plate viscometer. Flow cytometry was used to quantify the extents of platelet aggregation and of antibody binding to GPIIb/IIIa. Results indicate that c7E3 Fab injection resulted in a rapid, extensive blockade of GPIIb/IIIa receptors (98.6 +/- 0.2%) and a 50% inhibition of ex vivo platelet aggregation induced by shear stress. c7E3 Fab also completely abolished the formation of large platelet aggregates ("large" refers to particles > 10 microns in equivalent sphere diameter), which are presumably the aggregates of greatest clinical significance. Partial reversibility of the inhibition was noted within 2 days after drug administration, but even after 1 week, platelet function had not been fully restored. CONCLUSIONS: This study demonstrates that c7E3 Fab is a potent inhibitor of SIPA, which may be an important mechanism of its beneficial effect in the treatment of arterial occlusive diseases and in the prevention of thrombotic complications of coronary artery disease after angioplasty. PMID- 7867184 TI - Non-insulin-dependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes. The ARIC Study. Atherosclerosis Risk in Communities Study. AB - BACKGROUND: Cardiovascular diseases are the most common cause of disability and death among subjects with non-insulin-dependent diabetes mellitus (NIDDM). The atherosclerotic process begins during the prediabetic phase characterized by impaired glucose tolerance, hyperinsulinemia, and insulin resistance. In vitro studies have suggested that glucose and insulin can substantially alter the structure and function of the arterial wall and affect the development of atherosclerosis. METHODS AND RESULTS: We performed a cross-sectional study of the relation of arterial stiffness indexes with glucose tolerance and serum insulin concentrations. Several indexes of common carotid artery stiffness were assessed with noninvasive ultrasound methods in a biracial sample of 4701 men and women 45 to 64 years of age in the Atherosclerosis Risk in Communities (ARIC) Study. Arterial compliance (AC), stiffness index (SI), pressure-strain elastic modulus (Ep), and Young's elastic modulus (YEM) were calculated. YEM includes wall (intima-media) thickness and thus gives an estimate of arterial stiffness controlling for wall thickness. All indexes of arterial stiffness were higher with increasing concentrations of fasting glucose. This finding was consistent in both black and white examines and in both sexes. A 25% increase in fasting glucose (approximately 1 SD) was associated in nondiabetic white men with a 5.8% (95% CI, -9.6% to -1.9%; P = .004) decrease in AC and increases of 5.8% (95% CI, 2.0% to 9.7%; P = .002) in SI, 11.3% (95% CI, 6.9% to 15.9%; P < .001) in Ep, and 11.2% (95% CI, 6.2% to 16.6%; P < .001) in YEM. In nondiabetic white women, the corresponding predicted changes were a decrease of 15.0% (95% CI, -18.2% to 11.7%; P < .001) in AC and increases of 16.6% (95% CI, 12.5% to 20.8%; P < .001) in SI, 23.2% (95% CI, 18.4% to 28.2%; P < .001) in Ep, and 19.2% (95% CI, 14.0% to 24.7%; P < .001) in YEM. Glucose and insulin contributed synergistically to the increase in stiffness indexes. Insulin and triglycerides also had a synergistic association with stiffness indexes. CONCLUSIONS: Our findings are compatible with the view that persons with NIDDM or borderline glucose intolerance have stiffer arteries than their counterparts with normal glucose tolerance and that the decreased elasticity is independent of artery wall thickness. The joint effect of elevated glucose, insulin, and triglycerides can have a considerable impact on arterial stiffness and play an important role in the early pathophysiology of macrovascular disease in NIDDM. PMID- 7867185 TI - Paradoxical arterial wall shrinkage may contribute to luminal narrowing of human atherosclerotic femoral arteries. AB - BACKGROUND: This study was done to assess how local changes in vessel size, together with plaque load, determine luminal narrowing in atherosclerotic arteries. Fifty-one human femoral arteries were analyzed: 32 postmortem and 19 in vivo by 30-MHz intravascular ultrasound. METHODS AND RESULTS: Histological and intravascular ultrasound cross sections were examined every 0.5 cm over an arterial segment 10 to 15 cm long. In each cross section we measured the lumen area and the area circumscribed by the internal elastic lamina (the IEL area). In each arterial segment, the cross section that contained the least amount of plaque was the reference site. For each cross section, the lumen area stenosis was expressed as percent of the lumen area in the reference site. Similarly, the IEL area was expressed as percent of the IEL area in the reference site (the relative IEL area). There was a significant negative correlation between the relative IEL area and the lumen area stenosis percentage (r = -.62, P < .001 for histology and r = -.66, P < .001 for intravascular ultrasound). When lumen area stenosis was less than about 25%, mainly compensatory enlargement was observed. When lumen area stenosis exceeded about 25%, however, mainly a decrease of the IEL area was observed, which is consistent with arterial wall shrinkage. Furthermore, the increase in plaque area does not account for the total loss of luminal area. There was a moderate correlation between an increase in plaque area and reduction of the corresponding lumen area (r = .49 and r = .56 for histology and intravascular ultrasound, respectively). CONCLUSIONS: The decrease in luminal area cannot be attributed to plaque increase alone. Arterial wall shrinkage is a paradoxical mechanism that may contribute to severe luminal narrowing of the atherosclerotic human femoral artery. PMID- 7867186 TI - Increased serum concentrations of procollagen peptides in essential hypertension. Relation to cardiac alterations. AB - BACKGROUND: The serum concentrations of two procollagen-derived peptides, procollagen type III amino terminal peptide (PIIIP) and procollagen type I carboxy terminal peptide (PIP), have been proposed as useful markers of the tissue synthesis of collagen type III and type I, respectively. Therefore, this study was designed to evaluate fibrogenic activity in patients with essential hypertension by measuring serum PIIIP and PIP. Furthermore, since hypertensive heart disease is characterized by myocardial accumulation of collagen type III and type I, a second aim of the study was to assess whether some relation exists between the serum concentrations of PIIIP and PIP and several parameters of left ventricular anatomy and function in hypertensive patients. METHODS AND RESULTS: The study was performed in 50 patients with never-treated essential hypertension and in 30 normotensive control subjects. Measurements were repeated in 43 hypertensive patients after 6 months of treatment with the angiotensin-converting enzyme inhibitor lisinopril. The serum concentrations of PIIIP and PIP were measured by specific radioimmunoassay. Two-dimensional, targeted M-mode and Doppler ultrasound recordings were obtained in every subject to determine several parameters of the left ventricle anatomy and function. Ambulatory ECG monitoring was performed in each patient, and the recorded ventricular arrhythmias were categorized according to Lown-Wolf classification. Baseline serum PIIIP and PIP were increased (P < .001) in hypertensive patients as compared with normotensive subjects. An inverse correlation was found between serum PIIIP and the ratio between maximal early transmitral flow velocity and maximal late transmitral flow velocity measured during diastole (r = .3786, P < .01) in the group of hypertensive patients. Serum PIP was correlated directly with the left ventricular mass index (r = .3277, P < .05) in the group of hypertensive patients. Serum PIP concentrations increased in parallel with the increase in the grade of ventricular arrhythmias in the group of hypertensive patients. Treated patients attained normalization in blood pressure, amelioration of diastolic filling, regression of left ventricular mass index, and a diminution in the number of daily ventricular extrasystoles. In addition, serum PIIIP and PIP concentrations decreased significantly (P < .001) to normal values in patients treated with lisinopril. CONCLUSIONS: These findings suggest that tissue synthesis of collagen type III and type I is abnormally increased in essential hypertension and can be normalized by treatment with lisinopril. On the other hand, our results suggest that serum PIIIP and PIP are related to several anatomic and functional alterations of the hypertensive left ventricle. Serum procollagen peptide measurements may therefore provide indirect diagnostic information on the myocardial fibrosis associated with arterial hypertension. PMID- 7867187 TI - Angiotensin II. Adrenergic sympathetic constrictor action in humans. AB - BACKGROUND: Angiotensin II (Ang II) facilitates adrenergic neurotransmission in normotensive and hypertensive subjects, whereas angiotensin-converting enzyme inhibitors have been shown to depress circulating catecholamine concentrations in some studies. We investigated the effect of local intra-arterial infusion of Ang II into the brachial artery of healthy volunteers during blockade of postsynaptic alpha-receptors with phentolamine. The response was compared with that seen with Ang II infused during nitroprusside administration at a dose designed to give a dilator response similar to that with phentolamine. METHODS AND RESULTS: Ang II (6.25, 25, and 100 pmol/min) was infused alone and then together with sodium nitroprusside (4 micrograms/min) and phentolamine (40 micrograms/min) in eight healthy volunteers. Forearm blood flow was measured by strain-gauge plethysmography. The percentage reduction in forearm blood flow produced by Ang II 100 pmol/min in the phentolamine-predilated vascular bed was significantly lower than that seen in the sodium nitroprusside-predilated forearm bed (28.1 +/- 2.9% versus 52.9 +/- 4.2%; P = .006). Comparison of the rate of change of blood flow in response to quadrupling doses of Ang II during blockade of alpha receptors with phentolamine and during nitroprusside administration was calculated from the mean slope of the regression line of log-transformed blood flow versus dose of Ang II. The mean slope during nitroprusside administration ( 0.16 +/- 0.025) was significantly greater than that during blockade with phentolamine (-0.098 +/- 0.020) (P = .046). CONCLUSIONS: We conclude that a significant part of the vasoconstrictive action of exogenous Ang II on forearm resistance vessels in humans is sympathetically mediated. PMID- 7867188 TI - Regulation, chamber localization, and subtype distribution of angiotensin II receptors in human hearts. AB - BACKGROUND: To assess the chamber localization, subtype distribution, and regulation of human myocardial angiotensin II receptors in heart failure, we determined the binding of angiotensin II, Sar1Ile8-angiotensin II, and the subtype-specific antagonists Dup 753 (AT1-specific) and PD 123319 (AT2-specific) in atria from patients with normal (left ventricular ejection fraction > 55%) or moderately impaired (left ventricular ejection fraction 30% to 55%) cardiac function and in atria and ventricles from explanted end-stage failing hearts. Sarcolemmal and combined fractions, the latter including internalized receptors, were studied. In addition, AT1 mRNA content was analyzed by polymerase chain reaction after reverse transcription. METHODS AND RESULTS: The number of angiotensin II binding sites (Bmax) in sarcolemmal fractions was significantly reduced in explanted end-stage failing hearts in comparison with control subjects and moderate heart failure (Bmax 3.9 +/- 0.8 versus 11.2 +/- 1.7 and 9.6 +/- 0.8 fmol/mg protein, respectively). A comparable 65% reduction in receptor numbers was found in combined fractions from end-stage failing hearts, indicating that the loss of binding sites was not due to their internalization. The dissociation constants were comparable in sarcolemmal and combined fractions and in nonfailing and failing hearts, ranging from 0.5 +/- 0.2 to 1.2 +/- 0.5 nmol/L. In nonfailing hearts, 69 +/- 4% of binding sites were blocked by the subtype-2-specific inhibitor PD 123319 and were therefore classified as AT2; 33 +/- 5% were blocked by the subtype-1-specific inhibitor DUP 753 and thus classified as subtype 1. In explanted hearts, comparable ratios of 66 +/- 5% AT2 sites and 34 +/- 5% AT1 sites were found. AT1 cDNA amplification signals by polymerase chain reaction were reduced to about one third of the level in control subjects in end-stage failing hearts. CONCLUSIONS: Angiotensin II receptors in human myocardium are present in relatively low numbers, and AT2 is the predominant subtype. A significant loss of angiotensin II receptors occurs in end stage but not in moderate heart failure. The loss of receptors affects both subtypes to a comparable degree. The data suggest that the decrease in receptor density is due to a decrease in steady-state mRNA abundance. PMID- 7867189 TI - Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley Diabetes Study. AB - BACKGROUND: The ankle/brachial systolic blood pressure index (ABI), a noninvasive measure of peripheral arterial disease (PAD), is widely used in epidemiological studies. However, the normal ranges of the ABI in healthy populations and ABI criteria for the diagnosis of PAD in large population studies have not been critically evaluated. METHODS AND RESULTS: The San Luis Valley Diabetes Study (SLVDS) was designed to evaluate the prevalence and complications of non-insulin dependent diabetes mellitus (NIDDM) in a biethnic population. The present study was conducted as part of the SLVDS to assess the prevalence of vascular disease in 1280 nondiabetic control subjects and 430 patients with NIDDM. The ABI criteria for PAD were developed in 403 healthy individuals with a low risk for cardiovascular disease. In these low-risk subjects, the average resting ABI value was 0.07 lower in women than in men. In both sexes, the dorsalis pedis ABI was 0.04 lower than in the posterior tibial artery, and the left leg ABI was 0.02 lower than the right leg ABI (all differences, P < .05). In the low-risk subjects, ABI values were lower after exercise than at rest and had similar differences by sex and leg as observed at rest. Using specific abnormal cutoff points for the ABI, we evaluated three criteria for PAD in the overall population: two abnormal vessels in the same leg at rest (both dorsalis pedis and posterior tibial arteries), one abnormal vessel per leg at rest, and an ABI abnormality only after exercise. Subjects classified with PAD by the two-vessel criterion had a higher frequency of claudication and the physical finding of an absent pulse compared with subjects without PAD or patients with PAD defined by the one-vessel or exercise criterion. Use of the two-vessel criterion identified an increased risk of PAD with increasing age, NIDDM, smoking, hypertension, and elevated cholesterol levels. In contrast, the one-vessel PAD criterion was associated only with increasing age and smoking, and exercise-diagnosed PAD was not associated with any cardiovascular risk factor except for male sex. CONCLUSIONS: In low-risk subjects, the normal distribution and lower abnormal cutoff point values of the ABI differed by type of test, sex, ankle vessel, and leg. When these specific abnormal cutoff points were applied to the SLVDS population, the two-vessel abnormal criterion described patients with typical clinical characteristics of PAD and the expected associations of PAD with cardiovascular risk factors. These clinical characteristics and cardiovascular risk factor associations were less evident with PAD diagnosed by the one-vessel or exercise criterion. Therefore, an abnormal dorsalis pedis and posterior tibial ABI in the same leg at rest should be used for the diagnosis of PAD in epidemiological studies. PMID- 7867190 TI - Three distinct patterns of ventricular activation in infarcted human hearts. An intraoperative cardiac mapping study during sinus rhythm. AB - BACKGROUND: Comprehensive data based on single-beat analysis of the ventricular activation sequence during sinus rhythm in infarcted hearts are currently not available. It was the aim of our study (1) to measure and analyze these activation sequences on the epicardial surface of the right and left ventricles and on the left ventricular endocardial surface, and (2) to correlate specific activation patterns with the surface ECG. METHODS AND RESULTS: Isochronal maps were computed from 127 endocardial and epicardial unipolar electrograms recorded simultaneously during sinus rhythm in 45 post-myocardial infarction patients operated on for recurrent ventricular tachycardia (age, 57 +/- 10 years [mean +/- SD], left ventricular ejection fraction, 29 +/- 9%). Patients with bundle-branch block, but not with intraventricular conduction defects, were excluded. Data such as the timing of initial and terminal activation, the number of breakthroughs, the total activation time, and the number of ventricular segments without activation were measured and analyzed according to location of the myocardial infarction. The global epicardial activation was characterized in all patients by a widespread initial breakthrough on the anterior right ventricle (16 +/- 8 milliseconds after QRS onset), which was followed by one or two other breakthroughs in 65% of patients. Subsequently, three characteristic epicardial patterns of the activation spread were found: (1) radial, from the right to the left ventricle, found in all patients with inferoposterior myocardial infarction; (2) counterclockwise rotation, in which posteroseptal crossing preceded the anteroseptal crossing, found in 38% of patients with anterior myocardial infarction; and (3) pincerlike encirclement, in which both septal crossings and/or breakthroughs occurred nearly simultaneously and merged at the left ventricular free wall (typical for apical involvement in anterior and combined myocardial infarction). The simultaneous presence of multiple major activation wave fronts typically found in patients with the pincerlike activation pattern was reflected on the surface ECG by multiphasic, notched QRS complexes. Activation delay was observed in 89% of patients, and terminal activation was topographically related to myocardial infarction in 94% of patients. Delayed activation exceeding the surface QRS was observed in 11% and 31% of cases on the endocardium and epicardium, respectively. CONCLUSIONS: These results offer a solid basis for a more precise interpretation of a wide range of electrophysiological data and provide a framework for future investigations of surface ECG reflections of endocardial and epicardial activation patterns recorded in patients with chronic myocardial infarction. PMID- 7867191 TI - Optimal filtering and quality control of the signal-averaged ECG. High-fidelity 1 minute recordings. AB - BACKGROUND: The clinical performance of the signal-averaged ECG (SAECG) for prediction of ventricular tachycardia (VT) depends on its quality, or final noise level. However, signal averaging is a statistical estimation procedure that is time-consuming and vulnerable to noise-induced error. The optimally filtered SAECG is proposed as a simple, quality-assured procedure requiring only 1 minute of data. METHODS AND RESULTS: The optimally filtered SAECG is based on measures of signal variance and time-frequency representations. Forty subjects were studied to compare a 0.3-microV root-mean-square (RMS) noise endpoint SAECG with an optimally filtered 64-beat ensemble. Eight SAECGs were computed with noise endpoints of 1.0-through 0.3-microV RMS. Noise measurements were also made directly from the filtered SAECG. From these and previously published data, sensitivity was predicted as a function of noise endpoint. Measured QRS parameters and final noise were highly similar between the optimally filtered SAECG and the 0.3-microV RMS noise endpoint SAECG. CONCLUSIONS: The optimally filtered 64-beat SAECG achieves a performance (equivalent noise reduction, signal definition, and mathematically predicted sensitivity for VT) similar to a 0.3 microV RMS noise endpoint average. Testing in a large clinical database is required to validate the method for routine clinical use. SAECGs terminated by use of different noise measurement techniques are not directly comparable because of measurement technique dependence. However, a formula is presented for comparison of statistics between studies that have used the most popular noise measurement techniques. PMID- 7867192 TI - Catecholaminergic polymorphic ventricular tachycardia in children. A 7-year follow-up of 21 patients. AB - BACKGROUND: Primary ventricular tachyarrhythmias are rarely seen in children. Among them, catecholaminergic polymorphic ventricular tachycardia has a poor spontaneous outcome. Its diagnosis is often delayed after the first symptoms, which is unacceptable because treatment with the appropriate beta-blocker prevents sudden death. METHODS AND RESULTS: We observed 21 children (mean +/- SD age, 9.9 +/- 4 years) at the time of the diagnosis who had no structural heart disease and a normal QT interval on routine ECG. They were referred for stress- or emotion-induced syncope related to ventricular polymorphic tachyarrhythmias. The arrhythmia, consisting of isolated polymorphic ventricular extrasystoles followed by salvoes of bidirectional and polymorphic tachycardia susceptible to degeneration into ventricular fibrillation, was reproducibly induced by any form of increasing adrenergic stimulation. There was a familial history of syncope or sudden death in 30% of our patients. On receiving therapy with the appropriate beta-blocker, the patients' symptoms and polymorphic tachyarrhythmias disappeared. During a mean follow-up period of 7 years, three syncopal events and two sudden deaths occurred, probably due to treatment interruption. CONCLUSIONS: The entity of adrenergic-dependent, potentially lethal tachyarrhythmia with no structural heart disease deserves to be individualized. It may form a variant of the congenital long QT syndrome in which the ECG marker is lacking; this primary ventricular arrhythmia must be looked for in a pediatric patient with stress- or emotion-induced syncope because only beta-blocking therapy can prevent sudden death and therefore must be given for the patient's lifetime. PMID- 7867193 TI - Hypoxic stress induces cardiac myocyte-derived interleukin-6. AB - BACKGROUND: Hypoxic and ischemic stresses cause a series of well-documented changes in myocardial cells and tissues, including loss of contractility, changes in lipid and fatty acid metabolism, and irreversible membrane damage leading to eventual cellular death. Activated neutrophils are considered to be involved in this myocardial cellular injury. By stimulation of the neutrophils with chemotactic factors, canine neutrophils can be induced to adhere to isolated cardiac myocytes only if the myocytes have been previously exposed to cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6. METHODS AND RESULTS: To examine the possible involvement of IL-6 in ischemia-reperfusion injury, we used cultured rat neonatal cardiac myocytes to study the effects of hypoxic stress on the production of IL-6 by cardiac myocytes. Unstimulated cardiac myocytes (3 x 10(5) cells per dish) produced 320 pg IL-6 over 4 hours in vitro (ie, biological activity equal to 320 pg recombinant IL-6, as detected by bioassay using the MH-60.BSF2 cell line). The incubation of cardiac myocytes under hypoxic conditions for 4 hours induced significantly increased production of IL-6 compared with normoxic conditions (2.82 +/- 0.49 versus 1.64 +/- 0.18 U/mL, P < .05). Furthermore, reoxygenation for 2 hours after 2 hours of hypoxic stress significantly augmented the production of IL-6 by cardiac myocytes (4.34 +/- 0.52 U/mL, P < .05). These responses to hypoxia and reoxygenation were not observed in fibroblasts isolated from the same tissue. Although unstimulated cardiac myocytes lacked IL-6 mRNA expression detectable by Northern blot analysis, hypoxic stress induced the expression of IL-6 mRNA in the cardiac myocytes. Several pathophysiologically relevant factors also augmented IL-6 release from cultured cardiac myocytes, including IL-1 beta, ionomycin, and epinephrine. CONCLUSIONS: Cardiac myocytes respond to hypoxic stress to augment the production of IL-6, and the IL-6 derived from cardiac myocytes may play an important role in the progression of myocardial dysfunction observed in cardiac ischemia-reperfusion injury. PMID- 7867194 TI - Protection from oxidized LDL-induced leukocyte adhesion to microvascular and macrovascular endothelium in vivo by vitamin C but not by vitamin E. AB - BACKGROUND: The ability of oxidized LDL (oxLDL) to stimulate leukocyte endothelium interaction is considered to be an important aspect of its proatherogenic action. Using intravital fluorescence microscopy in the dorsal skinfold chamber model in hamsters, we have previously shown that systemic administration of oxLDL stimulates leukocyte adhesion to microvascular endothelium through a mechanism that involves the generation and action of reactive oxygen species (ROS). METHODS AND RESULTS: Through the combined use of scanning electron microscopy and intravital microscopy in the same animal model, we demonstrate that oxLDL-induced leukocyte adhesion is not confined to the microcirculation but can also be observed on aortic endothelium. OxLDL-induced leukocyte adhesion to both microvascular and macrovascular endothelium was almost entirely prevented by pretreatment of the hamsters with dietary or intravenous vitamin C, which has the capacity to scavenge and neutralize ROS (arterioles: 20.5 +/- 16.4 cells/mm2 [diet] and 16.3 +/- 23.8 cells/mm2 [IV] versus 74.2 +/- 47.5 cells/mm2 [control, P < .01]; aorta: 1.0 +/- 0.4 cells/mm2 [diet] and 1.1 +/ 0.5 cells/mm2 [IV] versus 14.7 +/- 6.0 cells/mm2 [control, P < .01], 15 minutes after oxLDL, n = 7 animals per group). Vitamin C pretreatment also completely prevented oxLDL-induced leukocyte-platelet aggregate formation in the blood stream but did not affect leukocyte rolling along the microvascular endothelium. No inhibitory effect on any of the studied parameters was observed as a result of pretreatment of the animals with the lipid-soluble antioxidants vitamin E and probucol. CONCLUSIONS: The protective effects of vitamin C on oxLDL-induced leukocyte adhesion and aggregate formation were seen at vitamin C plasma levels that can easily be reached in humans by diet or supplementation, suggesting that this could be one of the mechanisms by which vitamin C contributes to the well documented protraction of atherogenesis as observed in large epidemiological surveys. PMID- 7867195 TI - Endovascular low-dose irradiation inhibits neointima formation after coronary artery balloon injury in swine. A possible role for radiation therapy in restenosis prevention. AB - BACKGROUND: Restenosis after percutaneous transluminal coronary angioplasty remains a major limitation of the long-term success of this procedure. Restenosis is a form of wound healing. Low-dose ionizing radiation has been effective in inhibiting exuberant wound healing responses in a variety of clinical situations. METHODS AND RESULTS: Vascular neointimal lesions resembling human restenosis were created in the coronary arteries of normal pigs by overstretch balloon angioplasty injury. To test the effect of low-dose endovascular gamma radiation on lesion formation, a high-activity 192Ir source was introduced into one of the injured arteries in each animal and left in place for a period sufficient to deliver one of three doses: 350, 700, or 1400 cGy. To test potential benefits of delayed irradiation, 700 cGy was given in another group 2 days after injury. Animals were killed 14 days after balloon injury and the coronary vasculature was pressure-perfusion fixed. To test the late effect and safety of endovascular low dose irradiation, 700 or 1400 cGy was given in miniswine coronary arteries after injury as well as in noninjured carotid arteries; this group was followed up for 6 months. Tissue sections were measured by computer-assisted planimetry. All arteries treated with radiation demonstrated significantly decreased neointima formation compared with control arteries. The ratio of intimal area-to-medial fracture length (IA/FL) was inversely correlated with the different radiation doses: control, 0.59; 350 cGy, 0.38; 700 cGy, 0.42; and 1400 cGy, 0.17 (r = 0.75, P < .0001). Delay of 700-cGy irradiation for 2 days after injury significantly decreased neointima formation compared with the same dose given immediately after injury. Analysis of long-term specimens showed reduction of IA/FL in the arteries irradiated with 700 cGy (0.3, P = .009) and 1400 cGy (0.31, P = .001) compared with control arteries (0.50). There was no excess fibrosis in the media, adventitia, or perivascular space of the coronary arteries or adjacent myocardium in pigs that received radiation compared with control animals. CONCLUSIONS: Low-dose intracoronary irradiation delivered to the site of coronary arterial overstretch balloon injury in pigs inhibited subsequent intimal thickening (hyperplasia). A dose-response relationship was demonstrated, and delay of treatment for 48 hours appeared to augment the inhibitory effect. Six months of follow-up without fibrosis or arteriosclerosis demonstrated the durability of the beneficial effect in the treated group. These data suggest that intracoronary irradiation therapy may aid in preventing clinical restenosis. PMID- 7867196 TI - Comparison of the bleeding potential of vampire bat salivary plasminogen activator versus tissue plasminogen activator in an experimental rabbit model. AB - BACKGROUND: Vampire bat salivary plasminogen activator (Bat-PA) has significantly greater fibrin specificity than any of the fibrinolytic agents currently in clinical use. This study tests the hypothesis that avoiding fibrinogen depletion may protect against the hemorrhage induced by plasminogen activator treatment. METHODS AND RESULTS: Bat-PA was compared with tissue-type plasminogen activator (TPA) in a randomized, prospective, and blinded study using a rabbit ear puncture model of fibrinolytic bleeding. The two agents were used at equimolar dosages (42 nmol/kg) that yielded similar thrombolytic efficacies in a rabbit femoral artery thrombosis model. Both Bat-PA and TPA prolong primary bleeding to double the baseline values, from between 2.1 and 2.3 minutes to between 4.8 and 5.2 minutes. Rebleeding from hemostatically stable sites during the 3-hour observation period occurred equally often with Bat-PA and TPA, 31% from preinjection sites and 23% to 25% from postinjection sites. The lag time between the time of plasminogen activator injection and the onset of rebleeding was likewise the same for both agents, most occurring at 41 to 57 minutes. However, a greater number of prolonged primary or rebleeding occurrences continued for longer than 10 minutes (63% versus 36%) or longer than 30 minutes (30% versus 10%) after Bat-PA than TPA injection. Animals treated with TPA showed a dramatic decrease in plasma fibrinogen and factor VIII concentrations, but those in the Bat-PA treatment group showed only a slight decrease from control values. CONCLUSIONS: The results indicate that fibrinolytic bleeding after plasminogen activator infusion into rabbits did not correlate with the intensity of the plasma proteolytic state. If anything, Bat-PA usage was associated with a higher proportion of more protracted fibrinolytic bleeding episodes, despite the relatively mild lytic state in comparison with that induced by TPA. PMID- 7867197 TI - Inhibition of nitric oxide synthesis reduces infarct size by an adenosine dependent mechanism. AB - BACKGROUND: Nitric oxide (NO) is both a potent endogenous vasodilator with potential to attenuate ischemia-reperfusion injury and a mediator of tissue injury. The aim of the present study was to investigate the mechanism by which prior inhibition of NO synthesis can lessen ischemia-reperfusion injury in the isolated rabbit heart. METHODS AND RESULTS: We examined the effects of inhibition of NO synthesis on infarct size using a model of coronary artery ligation in isolated rabbit hearts perfused at a constant flow rate of 35 mL/min. Infarct size averaged 65% of the zone at risk after 45 minutes of ischemia and 180 minutes of reperfusion. The addition of 30 mumol/L NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, to the perfusate reduced the infarct-to-risk (I/R) ratio to an average of 41% (P < .05 versus control). This effect was abolished by pretreatment with 75.5 mumol/L 8-p-sulfophenyl theophylline (SPT), an adenosine receptor antagonist (I/R ratio, 63%). Ischemic preconditioning (5 minutes of ischemia and 10 minutes of reperfusion) before 45 minutes of ischemia and 3 hours of reperfusion reduced the I/R ratio to an average of 21%, and this was not augmented by pretreatment with L-NAME (I/R ratio, 20%). However, all protection due to preconditioning and L-NAME was lost in hearts pretreated with SPT (I/R ratio, 59%). In a separate set of experiments, adenosine concentration in the coronary perfusate and myocardial lactate concentrations were measured. Treatment with L-NAME increased the average adenosine concentration in the perfusate from 5.7 mumol/L per 100 g of heart (control) to a peak of 24.0 mumol/L per 100 g of heart; however, there was no effect on average myocardial lactate concentration (control, 4.6 mumol/g dry wt; L-NAME, 5.5 mumol/g dry wt). In contrast, after 5 minutes of global ischemia, the average adenosine concentration peaked at 139.0 mumol/L per 100 g of heart, and the average myocardial lactate concentration increased to 27.1 mumol/g dry wt. CONCLUSIONS: Infarct size limitation after inhibition of NO synthesis shares a common mechanism with that of ischemic preconditioning and is dependent on the release of adenosine. However, in this model, adenosine release after inhibition of NO synthesis is not secondary to myocardial ischemia. The protection of the heart against ischemic injury by adenosine appears to be concentration dependent. PMID- 7867198 TI - ST segment elevation at the surface of a healed transmural myocardial infarction in pigs. Conditions for passive transmission from the ischemic peri-infarction zone. AB - BACKGROUND: Ischemia of the myocardium surviving an infarction induces ST segment elevation in infarct-related ECG leads. In cases with no viable tissues, ischemia adjacent to the infarction could induce a similar ECG pattern if there is ST segment potential transmission through the necrotic scar. We analyzed whether acute ischemia adjacent to a healed infarction with no viable tissue may induce ST segment elevation on the surface of the necrotic scar. METHODS AND RESULTS: Epicardial ST segment changes elicited during 30 minutes of acute reocclusion of the left anterior descending (LAD) coronary artery 2 cm above the first diagonal branch were analyzed by 32-channel mapping in 18 chloralose-anesthetized open chest pigs with 1-month-old anterior infarctions induced by permanent ligature below the first diagonal branch (group 1). The effect of a previous infarction on the magnitude of ischemic ST segment changes was assessed by similar mapping in 21 control pigs submitted to a LAD ligature 2 cm above the first diagonal branch (group 2, n = 11) or just below this branch (group 3, n = 10). Myocardial perfusion after coronary ligature was estimated in 7 pigs with chronic infarction and in 3 control pigs by mapping of myocardial technetium-99m-methoxyisobutyl isonitrile (99mTc-MIBI) activity in transmural samples underlying each epicardial electrode. The width of cell layers surviving the infarction was measured and their viability after 60 minutes of coronary reocclusion was assessed by intracellular glycogen staining. Reocclusion of the LAD induced parallel ST segment elevation at the periinfarction zone and at the necrotic scar, although in the latter region the changes were less marked (maximal ST segment, 8.4 +/- 3.0 mV versus 2.7 +/- 1.8 mV, ANOVA, P < .001). ST segment elevation inside the scar was greater at the margins (3.9 +/- 1.8 mV) than at sites 20 mm toward the center (2.8 +/- 1.7 mV, P = .003). The necrotic area was virtually devoid of surviving cells except for a 0.22 +/- 0.04-mm-wide subendocardial band that continued to show a positive intracellular glycogen reaction after the second LAD ligature. Acute ischemia adjacent to the infarction (group 1) induced lower ST segment elevation than acute ischemia at a comparable cardiac region in noninfarcted pigs (group 2) (ANOVA, P = .02), despite the fact that these areas developed similar underperfusion after coronary occlusion (percent MIBI activity of that in normal myocardium, 7 +/- 8 versus 7 +/- 6, P = NS). ST segment changes in group 2 pigs were comparable to those induced in group 3 pigs with a 2-cm lower coronary occlusion. CONCLUSIONS: Acute ischemia adjacent to a chronic infarction induces ST segment elevation at the surface of the scar despite the virtual absence of viable tissue within the infarction. Data suggest a passive ST segment potential transmission through the infarction. Moreover, ischemia adjacent to a chronic infarction induces lower ST segment elevation than ischemia not adjacent to a necrosis. The mechanisms accounting for these regional differences are probably independent of collateral myocardial perfusion and ischemia extension. PMID- 7867199 TI - Effect of beta-adrenergic receptor blockade on blood flow to collateral-dependent myocardium during exercise. AB - BACKGROUND: beta-Adrenergic receptors have been identified in isolated coronary collateral blood vessels, but their functional significance in the intact heart has not been demonstrated. METHODS AND RESULTS: We measured myocardial blood flow with radioactive microspheres in normal and collateral-dependent myocardium in eight dogs trained to run on a treadmill before and after beta-adrenergic blockade with propranolol, 200 micrograms/kg, a dose that effectively inhibited the increase in coronary blood flow produced by selective beta 1- and beta 2 adrenergic agonists. Collateral vessel growth was stimulated with 2-minute intermittent occlusions of the left anterior descending artery followed by permanent occlusion. During control exercise, blood flow in the collateral zone was 38 +/- 5% less than in the normal zone. At identical levels of exercise, with heart rate maintained constant by atrial pacing, propranolol decreased mean blood flow in the collateralized myocardium from 1.93 +/- 0.17 to 1.50 +/- 0.14 mL.min 1.g-1 (P < .01), while increasing the subendocardial to subepicardial blood flow ratio from 0.78 +/- 0.11 to 0.91 +/- 0.10 (P < .05). The decrease in collateral zone blood flow in response to propranolol resulted from an increase in both transcollateral resistance from 25.9 +/- 2.3 to 35.2 +/- 4.3 mm Hg.mL-1.min.g (P < .05) and small-vessel resistance in the collateral-dependent myocardium from 30.9 +/- 4.7 to 44.0 +/- 8.8 mm Hg.mL-1.min.g (P < .07). Blood flow to the normal zone was also significantly reduced from 3.14 +/- 0.21 to 2.23 +/- 0.12 mL.min 1.g-1 (P < .01) after propranolol. CONCLUSIONS: beta-Adrenergic blockade decreased blood flow to collateral-dependent myocardium during exercise. These results indicate that beta-adrenergic receptor activation contributes to vasodilation of coronary collateral vessels during exercise. PMID- 7867200 TI - Activated clotting time as an appropriate test to compare heparin and direct thrombin inhibitors such as hirudin or Ro 46-6240 in experimental arterial thrombosis. AB - BACKGROUND: Specific thrombin inhibitors are considered to be more potent antithrombotics than heparin. However, the relation between the systemic anticoagulation generated by thrombin inhibitors and their antithrombotic effect is not well defined. In a guinea pig carotid thrombosis model, the activated clotting time (ACT), the activated partial thromboplastin time (aPTT), and thrombin-generation tests were evaluated for their ability to predict the arterial antithrombotic effect of direct thrombin inhibitors such as hirudin and Ro 46-6240 compared with heparin. METHODS AND RESULTS: Thrombosis of the carotid artery was induced by subendothelial damage in guinea pigs, and the subsequent cyclic flow variations were monitored. The effects of pretreatment with intravenous heparin, hirudin, and Ro 46-6240 were tested. After doubling the baseline aPTT, 1 IU.kg-1.min-1 heparin was inactive, whereas either hirudin or Ro 46-6240 (30 micrograms.kg-1.min-1) prevented thrombus formation by 80%. Heparin (10 IU.kg-1.min-1) induced the same antithrombotic effect but with indefinite aPTT prolongation. However, for similar prolongation of the ACT, the three compounds had equivalent antithrombotic effects. Thrombin generation was predictive of the antithrombotic effect of the thrombin inhibitors but not of heparin. CONCLUSIONS: The arterial antithrombotic effect of direct thrombin inhibitors, when compared with those of heparin, should be evaluated by the ACT and not the aPTT or thrombin-generation assays. For a "therapeutic" aPTT prolongation, thrombin inhibitors induce higher systemic anticoagulation than does heparin and thus might unduly have higher bleeding liability. PMID- 7867201 TI - Chronic rapid atrial pacing. Structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation. AB - BACKGROUND: Despite the clinical importance of atrial fibrillation (AF), the development of chronic nonvalvular AF models has been difficult. Animal models of sustained AF have been developed primarily in the short-term setting. Recently, models of chronic ventricular myopathy and fibrillation have been developed after several weeks of continuous rapid ventricular pacing. We hypothesized that chronic rapid atrial pacing would lead to atrial myopathy, yielding a reproducible model of sustained AF. METHODS AND RESULTS: Twenty-two halothane anesthetized mongrel dogs underwent insertion of a transvenous lead at the right atrial appendage that was continuously paced at 400 beats per minute for 6 weeks. Two-dimensional echocardiography was performed in 11 dogs to assess the effects of rapid atrial pacing on atrial size. Atrial vulnerability was defined as the ability to induce sustained repetitive atrial responses during programmed electrical stimulation and was assessed by extrastimulus and burst-pacing techniques. Effective refractory period (ERP) was measured at two endocardial sites in the right atrium. Sustained AF was defined as AF > or = 15 minutes. In animals with sustained AF, 10 quadripolar epicardial electrodes were surgically attached to the right and left atria. The local atrial fibrillatory cycle length (AFCL) was measured in a 20-second window, and the mean AFCL was measured at each site. Marked biatrial enlargement was documented; after 6 weeks of continuous rapid atrial pacing, the left atrium was 7.8 +/- 1 cm2 at baseline versus 11.3 +/ 1 cm2 after pacing, and the right atrium was 4.3 +/- 0.7 cm2 at baseline versus 7.2 +/- 1.3 cm2 after pacing. An increase in atrial area of at least 40% was necessary to induce sustained AF and was strongly correlated with the inducibility of AF (r = .87). Electron microscopy of atrial tissue demonstrated structural changes that were characterized by an increase in mitochondrial size and number and by disruption of the sarcoplasmic reticulum. After 6 weeks of continuous rapid atrial pacing, sustained AF was induced in 18 dogs (82%) and nonsustained AF was induced in 2 dogs (9%). AF occurred spontaneously in 4 dogs (18%). Right atrial ERP, measured at cycle lengths of 400 and 300 milliseconds at baseline, was significantly shortened after pacing, from 150 +/- 8 to 127 +/- 10 milliseconds and from 147 +/- 11 to 123 +/- 12 milliseconds, respectively (P < .001). This finding was highly predictive of inducibility of AF (90%). Increased atrial area (40%) and ERP shortening were highly predictive for the induction of sustained AF (88%). Local epicardial ERP correlated well with local AFCL (R2 = .93). Mean AFCL was significantly shorter in the left atrium (81 +/- 8 milliseconds) compared with the right atrium 94 +/- 9 milliseconds (P < .05). An area in the posterior left atrium was consistently found to have a shorter AFCL (74 +/- 5 milliseconds). Cryoablation of this area was attempted in 11 dogs. In 9 dogs (82%; mean, 9.0 +/- 4.0; range, 5 to 14), AF was terminated and no longer induced after serial cryoablation. CONCLUSIONS: Sustained AF was readily inducible in most dogs (82%) after rapid atrial pacing. This model was consistently associated with biatrial myopathy and marked changes in atrial vulnerability. An area in the posterior left atrium was uniformly shown to have the shortest AFCL. The results of restoration of sinus rhythm and prevention of inducibility of AF after cryoablation of this area of the left atrium suggest that this area may be critical in the maintenance of AF in this model. PMID- 7867202 TI - Cardiac disease in young trained athletes. Insights into methods for distinguishing athlete's heart from structural heart disease, with particular emphasis on hypertrophic cardiomyopathy. PMID- 7867203 TI - Images in cardiovascular medicine. Mirror-image dextrocardia with situs inversus. PMID- 7867204 TI - Morning resistance to thrombolytic therapy. PMID- 7867205 TI - Noninvasive coronary arteriography--here at last? PMID- 7867206 TI - What is the true periprocedure myocardial infarction rate? Does anyone know for sure? The need for clarification. PMID- 7867207 TI - Definition of postinfarction pericarditis. PMID- 7867208 TI - Effect of definition on incidence of postinfarction pericarditis: is it time to redefine postinfarction pericarditis? PMID- 7867209 TI - Spontaneous delayed recovery of perfusion and contraction after anterior infarction. PMID- 7867210 TI - Infantile dilated cardiomyopathy. PMID- 7867211 TI - Beta-adrenergic blockade and heart rate. PMID- 7867212 TI - Role of chemopreventers in human diet. AB - Recent research has confirmed that many common foods contain nonnutritive components that may provide protection against chronic disease including some forms of cancer. These naturally occurring compounds, which possess anticarcinogenic and other beneficial properties, are referred to as chemopreventers. The predominant mechanism of their protective action is due to their antioxidant activity and the capacity to scavenge free radicals. Among the most investigated chemopreventers are some vitamins, plant polyphenols, flavonoids, catechins, and some components in spices. The majority of chemopreventers are available in and consumed from vegetables, fruits, grains, and tea. Various naturally occurring chemicals in garlic, soybeans, tea, and red wine appear to be responsible for the beneficial effect of these commodities on several chronic diseases. This article will review some recent studies in the search for the beneficial effects of dietary chemopreventers on human health. PMID- 7867213 TI - Laboratory screening for genetic disorders and birth defects. AB - Screening for inherited disease is a preventative health measure that started in the 1960s with the development of programs for the detection of PKU in newborns and that has had a major impact on reducing the burden of disease. Developments in technology have led to the availability of large scale testing for an increasing number of both acquired and genetic disorders. Laboratory testing is only one facet of a screening program and consideration should be given to availability of testing to all individuals, education regarding the program, effectiveness of treatment, long-term benefits both for individuals and society, ethical issues, and cost benefits. In this review, newborn, prenatal, and heterozygote screening are discussed. PMID- 7867214 TI - Role of clinical laboratory in allergy testing. AB - The clinical laboratory has a well defined role to play in the diagnosis and management of patients with allergy. Elevated serum levels of total IgE and/or allergen-specific IgE indicate that an IgE mediated event has occurred. Methods such as basophil degranulation and basophil or leukocyte histamine release can provide similar information. Sensitive and precise methods suitable for automation are available for quantitation of histamine in whole blood or plasma. Methyl histamine can be assayed in urine. Eosinophil cationic protein levels in serum can be used as an indicator of eosinophil activation in disorders such as asthma and atopic dermatitis. Similarly, serum mast cell tryptase levels can confirm or exclude an anaphylactic reaction both in life and as a cause of death. This review documents and compares commercially available methods for these assays and discusses their application to screening, diagnosis, and management of patients with allergy. PMID- 7867215 TI - Detection of Philadelphia chromosome using PCR and europium-labeled DNA probes. AB - More than 95% of the patients with chronic myelogenous leukemia (CML) carry translocations between protooncogene abl of chromosome 9 and bcr gene of chromosome 22, resulting in the Philadelphia chromosome (Ph1). After allogeneic bone marrow transplantation (BMT) it is important to detect possible residual malignant cells in CML patients. A new sensitive hybridization method combined with polymerase chain reaction (PCR), based on the detection of the europium (Eu3+) label by time-resolved fluorescence, was applied for the detection of Ph1 chromosome. Total RNA from 10(6) peripheral blood leukocytes was isolated by the acid guanidinium thiocyanate-phenol-chloroform extraction. After cDNA synthesis by reverse transcriptase, the PCR amplification (30 cycles) was carried out. In the detection phase two oligonucleotide probes were used in the hybridization reaction, one biotinylated (bcr gene, exon 2) and one (abl gene) labeled with Eu3+. The hybrids were collected in a streptavidin-coated microtitration well and the bound Eu3+ was measured in a time-resolved fluorometer. To assess the sensitivity of the method, different numbers of CML cell line K562 cells were mixed with 10(5) apparently normal human leukocytes. Five K562 cells/10(5) leukocytes could be detected. Six patients with CML confirmed by clinical and cytogenetic criteria were studied. Three of the patients underwent an allogeneic BTM 6-18 months before the investigation and all of them were Ph1-negative. The other three patients who were nontransplanted were positive as expected. PMID- 7867217 TI - EMIT cyclosporine assay: development of an application protocol for Technicon AXON System. AB - Monitoring parent drug cyclosporine (CsA) concentrations in whole blood has been facilitated by the introduction of automated nonisotopic immunoassays [fluorescence polarization monoclonal whole blood assay (FPIA), EMIT Cyclosporine Assay]. The latter assay currently has a defined application only for Cobas Mira Chemistry Systems. The purpose of our work was to develop an application for this assay on the Technicon AXON. Instrument settings were optimized to arrive at the following assay performance characteristics. Limit of sensitivity was 50 micrograms/L. Interassay coefficients of variation (CV) were 11.2% (n = 16; mean = 81 micrograms/L) and 9.4% (n = 16; mean = 418 micrograms/L). Recoveries of 102, 112, and 117% were obtained by spiking aliquots of 10 whole blood patient pools of known CsA concentrations with 50, 100, and 200 micrograms/L CsA, respectively. Serial dilutions of two patient specimens demonstrated a linear relationship between expected and actual CsA concentrations (r = 0.996, 0.998; regression lines; y = 0.989x + 11.7; y = 0.979x + 9.5). Carryover and interference (lipemia) were not evident. Instrument calibration stability is at least 1 month. Comparison with CsA concentrations analyzed in renal transplant patients by the FPIA assay produced a linear regression equation of EMIT = 1.113x - 44.5, r = 0.968, Sy/x = 20.8, n = 32. Comparison with high-performance liquid chromatography (HPLC)-derived values in the same patient population produced a linear regression equation of EMIT = 1.114x - 16.4, r = 0.970, Sy/x = 20.2. FPIA derived CsA concentrations averaged 14.2% more than those obtained with the EMIT method with the latter averaging 1.3% more than HPLC values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867216 TI - Modified fluidity and lipid composition in lipoproteins and platelet membranes from diabetic patients. AB - The interaction between lipoproteins and the platelet membrane has been proved to cause a modification in cellular functions. We studied 12 men with insulin dependent diabetes mellitus (IDDM), 14 men with noninsulin-dependent diabetes mellitus (NIDDM), and 26 age-matched healthy men on the same diet. We determined fluidity by measuring the fluorescence polarization (P) of the probe 1,6-diphenyl 1,3,5-hexatriene (DPH) both in platelet membranes and in lipoproteins isolated by ultracentrifugation in NaBr density gradient. The lipid composition of lipoproteins and of platelet membranes was determined by enzymatic methods. The fluidity of platelet membranes was significantly increased both in patients affected by NIDDM and in subjects with IDDM compared with normal subjects. Low density lipoproteins (LDL) showed an increased fluidity only in NIDDM patients. A percent increase in the triglyceride content was observed in all lipoprotein fractions in diabetic subjects. Increased phospholipid content was found in the platelet membranes from IDDM and NIDDM patients. The change in LDL fluidity observed in NIDDM patients might determine altered interactions between the lipoprotein and cellular receptors. The role of lipoproteins in the modulation of the platelet membrane properties in diabetes mellitus deserves further studies. PMID- 7867218 TI - Combination (multiple) testing for myocardial infarction using myoglobin, creatine kinase-2 (mass), and troponin T. AB - We retrospectively determined the mass concentrations of myoglobin, creatine kinase-2 (CK-2), and troponin T in serial samples from 80 patients with confirmed myocardial infarction (MI) and 60 non-MI patients. Results from receiver operating characteristic curve analyses show that all three tests are comparable in their diagnostic utility within the first 12 h of infarction. Decision thresholds were selected at a constant rule-in specificity of 95% and rule-out sensitivities of 95% at, respectively, 3-6, 6-9, and 9-12 h intervals after the onset of symptoms. Test sensitivities and specificities were compared for each, used as: a single test; two-test parallel combination; three-test parallel combination; two-test series combination; and three-test series combination. Our results from combination testing indicate what for the early diagnosis of MI, a single serum myoglobin measurement has diagnostic utility at 3 h after the onset of symptoms, and myoglobin and CK-2 (mass) in combination later than 3 h following the onset of symptoms. Serum troponin T is diagnostically similar to CK 2 (mass), although it has superior cardiac-tissue specificity, but it is not as yet commercially available as a "stat" test. Therefore, we recommend using troponin T as a confirmatory test 9 h after the onset of MI. Based on our findings, we suggest a testing algorithm for the early biochemical diagnosis of MI. PMID- 7867219 TI - Prediction of serum markers of fibrosis by levels of circulating intercellular adhesion molecule-1 in acute and chronic liver disease. AB - To clarify the link between cytotoxic damage to the hepatocyte and the development of fibrosis, we immunoenzymatically measured serum prolyl hydroxylase (hPH), type IV collagen (CL-IV) and circulating intercellular adhesion molecule-1 (clCAM-1). The population studied was comprised of 122 patients with liver disease (acute hepatitis; mild chronic liver disease; cirrhosis; hepatocellular carcinoma) and 33 patients with extrahepatic diseases. Similar patterns were observed for hPH, CL-IV, and clCAM-1, that were higher in patients with acute hepatitis and hepatocellular carcinoma than in those with mild chronic liver disease (Bonferroni's test for pairwise comparisons, p < 0.01). Liver function tests and markers of fibrosis showed a strict correlation, which disappeared when the linear effect of clCAM-1 was removed. The ability to predict serum hPH and CL IV from clCAM-1 might suggest the existence of a causal relationship between fibrosis and targeting of cytotoxic damage. PMID- 7867220 TI - Oxidative enzymes of polymorphonuclear leucocytes and plasma fibrinogen, ceruloplasmin, and copper levels in Behcet's disease. AB - This study was performed to investigate the antioxidant mechanisms of polymorphonuclear leucocytes (PMN) in active stage of Behcet's Disease. PMN activities of myeloperoxidase (p < 0.02), superoxide dismutase (p < 0.001), catalase (p < 0.005), and glutathione peroxidase (p < 0.005) were significantly lower in the patients: the NADPH oxidase activity was significantly higher (p < 0.001) than those in controls. The plasma levels of ceruloplasmin (Cp), fibrinogen, and copper (Cu) were also significantly higher in the patients group (p < 0.001). Significant and positive correlations were found between the glutathione peroxidase and catalase activities (p < 0.001) and also between the plasma Cp and Cu levels (p < 0.001) in the patients group. However, no correlation was observed among the other enzyme activities. In the control group, a significantly positive correlation was present only between the plasma ceruloplasmin and Cu levels (p < 0.001). It was concluded that (impaired PMN functions) decreased enzyme activities in the antioxidant system and increased levels of oxygen free radicals may play a role in tissue damage in Behcet's disease. PMID- 7867221 TI - Consequences of a falsely elevated CA 125. PMID- 7867222 TI - Influence of protein and albumin levels on serum fructosamine concentration in a diabetic patient with multiple myeloma. PMID- 7867223 TI - Fast determination of myoglobin in serum using a new radial partition immunoassay. PMID- 7867224 TI - Autacoids and control of human placental blood flow. AB - 1. Humans have a haemochorial, villous placenta. Uterine blood passes through maternal sinuses, bathing placental villi through which fetal blood circulates. Blood flow through each circulation is high and vascular resistance low. This haemodynamic situation is essential for efficient placental function. 2. The low placental vascular resistance is due to a lack of nervous influences together with pregnancy-induced changes promoting vasodilatation. Increases occur in output of the vasodilators prostacyclin and nitric oxide and also in membrane sodium pump activity. 3. Many autacoids are present in umbilical blood. Fetal vessels of the placenta develop intense vasoconstriction in the presence of some autacoids, such as thromboxane A2 and prostaglandins F2 alpha and E2, and respond weakly to others, such as angiotensin II and 5-hydroxytryptamine. Nevertheless, vasodilator influences predominate. 4. The diseases of pre-eclampsia and fetal growth retardation are associated with reduced output of nitric oxide and prostacyclin and with increased production of thromboxane A2 and endothelin-1. These changes promote vasoconstriction, increased vascular sensitivity to vasoconstrictor stimuli, platelet aggregation and intravascular coagulation, retarding blood flow and feto-placental growth. 5. Aspirin and glyceryl trinitrate have been investigated for possible therapeutic use in pre-eclampsia and fetal growth retardation. Improved drug therapy is likely as knowledge increases of the importance of autacoids in normal placental function and in the changes that occur during disease. PMID- 7867225 TI - HBPRCA Astra Award. Therapeutic restoration of endothelial function in hypercholesterolaemic subjects: effect of fish oils. AB - 1. Endothelial dysfunction, evidenced as an impaired response to acetylcholine, is well documented in hypercholesterolaemic subjects. We examined the ability of dietary supplementation with fish oils to restore endothelial function in forearm resistance vessels in these patients and compared this with restoration by lipid lowering therapy. 2. Responses of forearm blood flow to acetylcholine (4.6, 9.25, 18.5 and 37 micrograms/min) and sodium nitroprusside (200, 400, 800 and 1600 ng/min) were obtained using forearm venous occlusion plethysmography in nine hypercholesterolaemic and seven age-matched control subjects. The dose-response curve to acetylcholine was significantly blunted in hypercholesterolaemic subjects when compared with controls (P < 0.001). Responses to sodium nitroprusside were not different between the two groups (P = 0.37). 3. Lipid lowering therapy decreased total plasma cholesterol levels by 33% and significantly augmented the responses to acetylcholine (P = 0.001) but not to sodium nitroprusside in the hypercholesterolaemic subjects. 4. Dietary supplementation with fish oils had no effect on either total or low density lipoprotein-cholesterol but significantly augmented the responses to acetylcholine (P = 0.011) in hypercholesterolaemic subjects. Responses to sodium nitroprusside were not altered (P = 0.94). 5. This study shows that endothelium dependent relaxation is impaired in subjects with high cholesterol levels and that this impairment can be reversed by lowering low density lipoproteins (LDL) cholesterol levels. In addition, we demonstrate that restoration of endothelial function can occur without changes in LDL levels, by dietary supplementation with fish oils. PMID- 7867226 TI - Long-term clenbuterol administration alters the isometric contractile properties of skeletal muscle from normal and dystrophin-deficient mdx mice. AB - 1. This study was designed to establish whether long-term treatment with the powerful anabolic agent clenbuterol has beneficial effects on dystrophin deficient skeletal muscle function. 2. Normal (C57BL/10) and dystrophic (mdx) mice were administered clenbuterol (2 mg/kg per day) for 15 weeks. At 20 weeks of age, the extensor digitorum longus (EDL) and soleus muscles were removed, and their contractile and histochemical properties analysed. 3. Absolute and relative muscle masses were larger (P < 0.001) in mdx compared to C57BL/10 mice. These larger muscles produced larger absolute forces (P < 0.01) in the soleus of mdx mice compared to normal mice. Relative tetanic force was also larger (P < 0.05) in the soleus of mdx mice. In contrast, the absolute tetanic tension of the EDL was reduced (P < 0.01) in mdx mice compared to C57BL/10 mice, and both relative twitch and tetanic tensions were also lower (P < 0.001) in mdx mice. 4. Clenbuterol increased the lean muscle mass in both normal (10%, P < 0.05 and 20%, P < 0.01 for the EDL and soleus, respectively) and dystrophic (7%, P < 0.05 and 11%, P < 0.01) groups. Twitch contraction times were significantly faster in both the EDL (P < 0.001) and soleus (P < 0.01) muscles following clenbuterol administration, supported by fibre-type transitions towards fast-twitch fibres. Relative force levels of the soleus muscle of both C57BL/10 (40%, P < 0.01) and mdx (20%, P < 0.01) mice were increased significantly following clenbuterol treatment. No changes in the absolute or relative forces of the EDL muscles were observed in response to clenbuterol administration. 5. Clenbuterol was thus able to increase the force output of a slow-twitch, mixed (hence human-like) muscle but not fast-twitch muscle from mdx mice. The results lend tentative support to the potential role of clenbuterol as an anabolic agent in the treatment of muscle wasting diseases. PMID- 7867227 TI - Augmentation of angiotensin II release from isolated mesenteric arteries of Wistar-Kyoto and spontaneously hypertensive rats following nephrectomy. AB - 1. We previously reported that angiotensin II release from the mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) increased in a time-dependent manner as a result of the isolation of the arteries and perfusion. This phenomenon appeared to be due to the withdrawal of circulating angiotensin II (AII). 2. The purpose of the present study was to test the hypothesis that vascular AII generation may be negatively regulated by circulating AII in WKY and SHR, and to clarify the role of this vascular angiotensin II in the sustained hypertension of SHR following nephrectomy. 3. The mesenteric arteries from kidney-intact and nephrectomized WKY and SHR were perfused and the amount of AII released into the perfusate was measured. The effects of the angiotensin converting enzyme inhibitor, captopril, and the effects of supplementation of renal renin and circulating angiotensins to nephrectomized rats, by blood exchange between kidney-intact and nephrectomized rats, on AII release were examined to clarify the pathway of vascular AII generation after nephrectomy. 4. Nephrectomy caused augmentation of vascular AII release both in WKY and SHR in spite of the abolishment of circulating renin. Captopril reduced this enhanced release of AII, but blood exchange did not affect it. There was no significant difference in these responses between WKY and SHR. 5. These results suggest that WKY and SHR have in common a potent pathway for production of vascular AII in response to the withdrawal of circulating AII, although this pathway is not responsible for the sustained hypertension of SHR after nephrectomy. The precise pathophysiological role of this pathway remains to be elucidated. PMID- 7867228 TI - Effect of atrial natriuretic peptide on cellular element concentrations in rat proximal tubules: evidence for inhibition of the sodium pump. AB - 1. In order to further define the action of atrial natriuretic peptide (ANP) on proximal tubular (PT) transport, combined clearance and electron microprobe X-ray (EMPX) experiments were performed on five male Wistar rats infused with ANP (0.16 nmol/kg per h) and nine control animals. 2. Electron microprobe X-ray analysis of PT cell electrolytes (mmol/kg wet weight) revealed a similar [Na]i in both the control and ANP treated groups (16.4 +/- 0.4 vs 16.5 +/- 0.4; P = 0.894). [Cl]i was lower in the ANP treated animals (14.8 +/- 0.3 vs 12.0 +/- 0.3; P < 0.0001) as was [K]i (131.4 +/- 1.4 vs 114 +/- 1.7; P < 0.0001). The PT cells in the ANP treated group had a significant reduction in dry weight (20.1 +/- 0.3 g% vs 19.0 +/- 0.3 g%; P < 0.024), indicating significant cell swelling. Thus, despite a normal [Na]i, there was net accumulation of Nai following ANP treatment. 3. These results are consistent with accumulation of Nai due to inhibition of the Na pump followed by cell swelling and subsequent regulatory volume decrease with exit of K and Cl. These results are the first to show the effect of ANP on PT intracellular electrolytes. PMID- 7867229 TI - Control of coronary blood flow by endothelial release of nitric oxide. AB - 1. Nitric oxide (NO) is released from vascular endothelium following conversion of L-arginine to L-citrulline by calcium-calmodulin-dependent 'constitutive' NO synthase. 2. Nitric oxide release occurs under basal conditions, in response to chemical stimuli (acetylcholine, bradykinin, thrombin, prostacyclin, serotonin, etc.) and in response to changes in shear stress (effects of blood velocity on vascular endothelium). 3. Analogues of L-arginine inhibit NO and are widely used to study the effects of NO on the cardiovascular system: in intact animals, these inhibitors cause vasoconstriction, leading to an increase in arterial blood pressure (ABP) and bradycardia. 4. Bradycardia induced by NO inhibitors is due, in part, to baroreceptor activity following the increase in ABP and in part to a direct effect on the sino-atrial node. 5. In the intact animals and isolated perfused heart, NO inhibitors cause coronary vasoconstriction and hence a reduction in basal coronary flow. This effect, however, is not seen in isolated coronary vessels. 6. From experiments in which ABP did not change, NO does not appear to have an important role in regulating coronary vasomotor tone under basal conditions. 7. Nitric oxide appears to be involved in the duration of reactive hyperaemia following coronary vascular occlusion but is not involved to any significant extent in the peak amplitude of hyperaemia. 8. Responses to vasodilator stimuli which do not involve NO in the initiation of the vasodilation may be prolonged by the effect of increased blood flow (shear stress) which releases NO and potentiates hyperaemia. PMID- 7867230 TI - Cardiac baroreflexes and hypertension. AB - 1. The role of cardiac reflexes in baroreflex control mechanisms and the changes that occur in chronic hypertension is reviewed. The rapid resetting properties of the arterial baroreceptors ensures its role in short-term rather than long-term control of blood pressure. 2. In hypertensive humans and animals, the baroreceptor-heart rate reflex has diminished sensitivity due mainly to reduced maximum capacity of the cardiac vagal component rather than a change to the sympathetic. 3. The development of this vagal deficit in spontaneously hypertensive rats (SHR) coincides with the onset of cardiac hypertrophy rather than vascular hypertrophy. A combination of chronic perindopril treatment regimens in young and older SHR showed that the vagal deficit was better correlated with the degree of cardiac hypertrophy than with other variables such as blood pressure, hypertension or indices of vascular hypertrophy. Similar results have been shown for renovascular hypertension in rats. 4. The bradycardia produced by electrical stimulation of the vagus in urethane anaesthetized young SHR was enhanced compared to Wistar-Kyoto rats (WKY) while responses observed in adult SHR and WKY were similar, suggesting that the vagal deficit in hypertensive rats is not due to a defect in the efferent arm of the baroreflex. 5. The association of the vagal deficit with cardiac hypertrophy, but not with the vagal efferent pathways, suggests an important role for cardiac afferents in hypertension in mediating the baroreflex deficit. 6. A diminished baroreflex and also a reduced heart rate variability is an independent risk factor for sudden death following myocardial infarction. Thus, antihypertensive therapy, which more effectively reduces cardiac hypertrophy, should have a desirable effect on baroreceptor reflexes and therefore in reducing blood pressure variability. PMID- 7867231 TI - The effects of sympathomimetics on the cardiovascular system of sheep. AB - 1. Sheep hearts have been used to study the effects of beta-adrenoceptor (beta AR) agonists in order to better understand the effects of common asthma treatment drugs on heart rate, cardiac power output and cardiac pathology. Hearts have been examined both in vivo and in vitro. 2. In whole anaesthetized sheep, isoprenaline, fenoterol and salbutamol induced dose-dependent increases in heart rate. Hypokalaemia in response to salbutamol was accentuated in hypoxia. Many of these hearts showed significant myocardial lesions. Hypoxia alone caused no significant cardiac response. 3. As expected, the beta 1-AR agonist dobutamine caused dose-dependent increases in heart performance (heart rate and cardiac power output). Both responses were blocked by metoprolol and propranolol. The beta 2-AR agonist salbutamol caused dose-dependent increases in heart rate and although cardiac output increased, cardiac power output remained unchanged as a consequence of the fall in peripheral resistance. The heart rate changes were blocked by metoprolol. Importantly, propranolol blocked both the heart rate response and the fall in peripheral resistance. 4. Isolated atrial strips showed a right shift of their dose-response curve to isoprenaline in the presence of the highly selective beta 2-AR antagonist ICI 118,551 at concentrations above 1 x 10( 8) mol/L. 5. We conclude that the sheep heart shows many pharmacological characteristics of the human heart which makes it a good pharmacological model in addition to its being amenable to many common techniques available for humans. PMID- 7867232 TI - Angiotensin receptors in cardiovascular diseases. AB - 1. Angiotensin II (AII) plays a major role in cardiovascular function via direct actions on the vasculature, kidney, adrenal, heart, brain and sympathetic nerves. The cellular effects of AII are extensive and encompass hypertrophy, hyperplasia and the deposition of extracellular matrix. 2. The actions of AII are mediated by the AT1 and AT2 membrane receptor subtypes, and additional forms of each subtype. Evidence is emerging that selective changes in AII receptor subtypes occur in cardiovascular diseases. 3. Thyroid dysfunction increased cardiac, liver and kidney AII receptor density but decreased adrenal gland receptor density. In the heart, there was a selective increase in AT2 receptor density. 4. Diabetes increased cardiac, liver and adrenal gland AII receptor densities but decreased kidney receptor density. 5. Hypertension increased AII receptor density in the heart and kidney. A corresponding increase in receptor mRNA was prevented by selective AT1 receptor antagonists. 6. The human heart contained AII receptors in all chambers; right atrial receptor density was increased in coronary artery bypass graft patients. 7. The presence of AII receptor changes in these models of cardiac hypertrophy and hypertension raises the possibility of using orally active, subtype-selective agonists and antagonists to treat particular forms of cardiovascular diseases. PMID- 7867233 TI - Central neurons and neurotransmitters in the control of blood pressure. AB - 1. In this paper we review recent work from our laboratory on two major pathways important in the central control of blood pressure. 2. We report experiments on the sympatho-excitatory bulbospinal pathway from the rostral ventral medulla. Here we focus particularly on the role of excitatory amino acids. 3. We review studies on the short inhibitory or depressor pathway ascending from the caudal to the rostral ventral medulla, which is thought to use gamma-aminobutyric acid (GABA) as its neurotransmitter. We report on experiments with the immediate early gene, c-fos, demonstrating that its expression in the bulbospinal pressor neurons is increased by stimuli that activate these nerves, and that this expression can be blocked in vivo by treatment with an antisense oligonucleotide. We also show that basal and stimulated expression of the c-fos gene is important in the central control of blood pressure. PMID- 7867234 TI - Atrial fibrillation, transesophageal echo, electrical cardioversion, and anticoagulation. AB - Although successful electrical cardioversion is accomplished in most cases without any evidence of embolic stroke, a few patients have experienced this catastrophe. The current thinking is that when electrical energy is applied to the chest wall, the atrium, although it returns to sinus rhythm, is stunned. It is not known how long this stunning lasts in the individual patient nor whether high energy produces stunning and low energy does not. Nor is it known whether chemical conversion of atrial fibrillation to sinus rhythm affects the atrium in the same way. However, the atrium seems to recover more quickly in patients with a short duration of atrial fibrillation and these patients may not require the usual four weeks of postcardioversion anticoagulation. Based on what we know, or more precisely what we don't know, it seems reasonable to ensure that every patient with atrial fibrillation is anticoagulated during and after DC cardioversion to sinus rhythm. Of course, this is easy to do with intravenous heparin, but that requires hospitalization. Perhaps subcutaneous heparin in high doses would suffice until the patient can be anticoagulated with coumadin. From the research perspective it might be interesting to perform serial echo/Doppler studies on these patients to identify when the individual patient's atrial function returns to normal. This might provide a clinical rationale for discontinuing anticoagulation. Comparing the time to return of normal atrial function (as measured by Doppler echo) between patients undergoing pharmacologic cardioversion versus electrical cardioversion and studying the relationship of the amount of electrical energy required for cardioversion versus the duration of stunning would be clinical research projects of interest to clinicians. PMID- 7867235 TI - Is there a role for positive inotropic agents in congestive heart failure: focus on mortality. AB - Congestive heart failure (CHF) is a common clinical syndrome that may result from a variety of etiologies. Impaired contractility can lead to pump failure and a number of hemodynamic and neurohormonal alterations. Vasodilator therapy improves symptoms and survival in patients with CHF due to systolic dysfunction. Inotropic therapy, on the other hand, has not been shown to improve survival and may even worsen survival. This article reviews the mechanism of action and clinical trials of inotropic therapy in patients with CHF. PMID- 7867236 TI - Percutaneous transvenous mitral commissurotomy for restenosis after surgical mitral valvotomy. AB - Percutaneous transvenous mitral commissurotomy (PTMC) was performed in 350 patients. Of these patients, 51 (15%) (30 women and 21 men, aged 32 +/- 11 years) had restenosis 11 +/- 4 years following surgical valvotomy. Forty (79%) patients were in New York Heart Association (NYHA) class III and 11 (21%) were in class IV. PTMC resulted in an increase in mitral valve area from 0.82 +/- 0.3 to 1.9 +/ 0.2 cm2 (p < 0.001), an increase in cardiac index from 1.9 +/- 0.4 to 2.8 +/- 0.5 l/min/m2 (p < 0.001), and a decrease in mean transmitral gradients from 29 +/ 4 to 6 +/- 4 mmHg (p < 0.001). The results did not differ from those observed in 299 patients without prior surgical valvotomy. On univariate analysis, the subvalvular fibrosis, assessed angiographically, and the duration from prior surgery were not found to influence the overall outcome. At 24 weeks, 46 of 48 (96%) patients in whom clinical follow-up was available, were found to be in NYHA class I and 2 (4%) patients were in class II. Thus, PTMC is a safe and effective procedure for patients with mitral restenosis following surgical valvotomy. PMID- 7867237 TI - Cardiocirculatory and metabolic strain during rowing ergometry in coronary patients. AB - To investigate the suitability of rowing for cardiac rehabilitation, the cardiocirculatory and metabolic reactions during rowing (RE) and cycle (CE) ergometry were compared. Ten male normotensive subjects of an outpatient heart group (age 56 +/- 7 years, maximum performance on CE 2.0 +/- 0.4 W.kg-1) carried out a stepwise increasing test on an isokinetic rowing ergometer and a CE (increasing by 25 W every 3 min). In a 1-min break after each step, heart rate and blood pressure, blood concentrations of lactate, and the free catecholamines adrenaline and noradrenaline were measured. Four patients showed signs of myocardial ischemia occurring almost one step earlier on RE than on CE. In RE, the endurance and maximum performance were about 20 W lower than on CE. At similar workloads, heart rate, blood pressure, and concentrations of lactate and catecholamines measured significantly higher on RE than on CE. At workloads above the individual anaerobic threshold, the increase in adrenaline and noradrenaline was significantly higher on RE than on CE. The results can be explained by the lower work efficiency, the higher isometric demands with increased cardiac pressure load, and the higher mental stress in RE. Rowing is only suitable in cardiac rehabilitation when well-defined prerequisites have been considered. PMID- 7867238 TI - A clinical and in vitro study on the possible interaction of intravenous nitrates with heparin anticoagulation. AB - It has been reported that intravenous nitrates inhibit the anticoagulant effect of heparin. This possible interaction has potentially serious implications for the management of patients with acute coronary ischemic syndromes. This possible interaction was assessed prospectively in a clinical and in an in vitro study involving 24 patients receiving both drugs for the management of unstable angina pectoris. There was a small inhibitory effect of intravenous glyceryl trinitrate or isosorbide dinitrate on the anticoagulant effect of heparin in 3 of 24 cases in vivo, as assessed by activated partial thromboplastin time measurements. Nitrates or propylene glycol had no effect on heparin activity in vitro. It was concluded that there may be an inhibitory effect of nitrates on anticoagulation in a small minority of patients, but close attention to detail in monitoring heparin anticoagulation is far more important. PMID- 7867239 TI - Noninvasive evaluation of contractile state by left ventricular dP/dtmax divided by end-diastolic volume using continuous-wave Doppler and M-mode echocardiography. AB - The maximum rate of left ventricular (LV) pressure rise (dP/dtmax) is commonly used in the assessment of directional change in LV contractility and, recently, estimated by analyzing continuous-wave Doppler ultrasound velocity curve of mitral regurgitation. As an alteration in ventricular preload is known to affect dP/dtmax, normalized dP/dtmax for preload might be more reliable to assess LV contractile state. To investigate the usefulness of a new index of LV contractile state determined by continuous-wave Doppler analysis of mitral regurgitation and M-mode echocardiogram-derived LV end-diastolic volume, we studied 18 patients with mild mitral regurgitation. The continuous-wave Doppler velocity curves of mitral regurgitation were digitized and converted to instantaneous pressure gradient between the LV and left atrium using the simplified Bernoulli equation. The maximum value of its first derivative (Doppler-derived dP/dtmax) correlated well with LV dP/dtmax using simultaneously recorded LV pressures by manometer tipped catheter (n = 20, r = 0.97, p < 0.001). Corrected Doppler-derived dP/dtmax for LV end-diastolic volume using Teichholz's method significantly increased by inotropic stimulation with dobutamine (p < 0.01); however, it remained unchanged by augmentation of afterload with angiotensin II. Thus, the LV dP/dtmax can be accurately estimated in humans by analyzing the continuous-wave Doppler velocity curve of mitral regurgitation, and corrected Doppler-derived dP/dtmax for LV end diastolic volume is relatively independent of loading alteration and sensitive to inotropic stimulation. We concluded that echocardiographic assessment by combined Doppler- and M-mode measurements provides a useful and sensitive index of LV contractile state noninvasively. PMID- 7867240 TI - Effects of atenolol and diltiazem-SR on exercise and pressure load in hypertensive patients. AB - The effects of monotherapy with atenolol or diltiazem-SR on blood pressure, 24-h blood pressure (BP) load, and exercise capacity were tested in patients with mild to moderate (stages I and II) essential hypertension. After 3-week single-blind placebo therapy, patients with sitting diastolic blood pressure (SDBP) of 94-114 mmHg were randomized to atenolol 50 mg/day (62 patients) or diltiazem-SR 90 mg b.i.d. (60 patients) in a double-blind parallel study. Depending on SDBP response, the dose was increased to 100 mg/day for atenolol and 180 mg b.i.d. for diltiazem-SR. Twenty-four-hour ambulatory blood pressure measurements and exercise tolerance test by the Bruce protocol were done at the end of placebo and active treatment. Compared with placebo, both atenolol and diltiazem-SR significantly decreased heart rate (HR), sitting systolic blood pressure (SSBP), SDBP, ambulatory BP, BP load for waking and sleeping hours, area under the BP curve, rate-pressure product (p < 0.001), and exercise time (NS). Atenolol exerted a greater effect on ambulatory BP, HR, rate-pressure product, waking diastolic BP load, and area under the 24-h BP curve. The drugs were well tolerated and caused no serious side effects necessitating discontinuation of treatment. These findings indicate that (1) monotherapy for hypertension with atenolol or diltiazem-SR is effective and well tolerated, (2) it decreases the 24 h BP load, (3) it does not interfere with exercise capacity. PMID- 7867241 TI - Sleep apnea and complete heart block. AB - Sleep apnea has been associated with various types of cardiac dysrhythmias; however, complete heart block has not been reported to occur in this condition. This brief report describes the case of a patient who developed episodes of prolonged complete heart block during sleep apnea. Nasal continuous positive airway pressure resulted in complete resolution of the heart block. PMID- 7867242 TI - High cardiac output state in patients with multiple myeloma: case report and review of the literature. AB - A high cardiac output state, with or without congestive heart failure, has recently been recognized in patients with multiple myeloma. This case report deals with a 62-year-old man with multiple myeloma refractory to treatment, a high cardiac output state, and life-threatening pulmonary edema. In addition, a brief review of the literature is presented. PMID- 7867243 TI - Myron Prinzmetal. PMID- 7867244 TI - The effect of heat shock on immediate post-preservation lung function. AB - Exposure of animals to transient hyperthermia causes the induction of highly conserved proteins, heat shock proteins (HSPs), which are thought to by cytoprotective against a variety of injuries, including ischemia. We tested the hypothesis that heating donor animals prior to harvest would improve pulmonary preservation. Anaesthetized New Zealand White rabbits underwent radiant heating to 42.5-43.5 degrees C (rectal) 8 h prior to harvest of the lungs. The lungs were harvested without flush and stored for 18 h at 4 degrees C. The left lung were perfused ex vivo with fresh blood for 10 min. Blood gases, pulmonary artery (Ppa) and airway (P(aw) pressures, and wet/dry ratios (W/D) were measured. Control animals were treated identically except without heating. All heated animals had HSP72 at lung harvest and 18 h later, whereas no control had detectable levels of HSP72 at either time. In Experiment 1 (n = 12, VT 20 ml, F1O2 0.21, 30 bpm, PEEP 0.5 cm H2O), PO2 in the heated group was 57.6 +/- 7.3 mmHg (mean +/- SEM) vs. 51.6 +/- 5.7 in the controls (NS). In Experiment 2 (n = 8, VT 15 ml, F1O2 0.21, 35 bpm, PEEP 2 cm H2O), PO2 of the heated group was 63.5 +/- 6.5 vs. 83.1 +/- 9.5 in the controls (NS). Ppa after 10 min was not significantly different in the heated group in Experiment 1 (16.7 +/- 0.9 mmHg vs. 24.2 +/- 3.7 in controls) or in Experiment 2 (19.5 +/- 1.8 vs. 11.3 +/- 2.9 in controls). Wet/dry ratios were not different in either Experiment 1 (6.4 +/- 0.4 vs. 5.8 +/- 0.2 in controls) or Experiment 2 (5.0 +/- 0.2 vs. 5.0 +/- 0.5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867245 TI - Hyperkalemia with mild ECF volume contraction: studies to provide a possible physiologic interpretation. AB - A 30-y-old female presented with a history of hypertension and a modest degree of hyperkalemia. There was a mild degree of contraction of her ECF volume on clinical examination, with elevated levels of renin and aldosterone in plasma. No causes for secondary hypertension were found. Laboratory investigations revealed a slightly reduced glomerular filtration rate (GFR) and a subnormal kaliuretic response to exogenous mineralocorticoids. When a further degree of ECF volume contraction was induced, she was unable to conserve Na+ and Cl- appropriately. Moreover, expansion of the ECF volume led to a significant suppression of the levels of both renin and aldosterone in plasma. We speculate that these findings could be explained by a diminished net rate of reabsorption of Na+ in the cortical collecting duct. Such a reduction could lead to a diminished generation of an electrical gradient to favour the net secretion of K+ and lead to hyperkalemia with renal salt wasting. The resultant contraction of the extracellular fluid volume with the release of renin and aldosterone (and probably other vasoactive hormones) might have predisposed her to hypertension. This hypothesis was supported by the finding that NaCl supplements led to a significant drop in her blood pressure. This case could represent a new syndrome of hyperkalemia and "salt sensitive" hypertension. PMID- 7867246 TI - Tissue disposition of 26aluminum in rats measured by accelerator mass spectrometry. AB - A trace quantity of 26aluminum (26Al) was administered intravenously to 1 normal and 1 uremic rat. After a 3-week period, the animals were sacrificed and samples of bone, muscle, kidney, liver, heart, and brain were analyzed for their 26Al content. In the normal and uremic rats, most of the tissue 26Al was found in bone amounting to 0.9% and 2.0%, respectively, of administered dose/g dry weight of tissue. Much smaller amounts of isotope were found in the other tissues in both animals. In the normal rat, the descending order of 26Al content in other tissues was: kidney, 0.2% > liver, 0.06% > heart, 0.03%, > brain and muscle, 0.02%. In the uremic rat, the same order of tissue 26Al content was found with kidney, 0.37% > liver, 0.06% > heart, 0.02% > brain and muscle, 0.01% per g dry weight of tissue. When expressed per g wet weight of tissue in the 2 animals, a similar order of tissue 26Al content was found. In comparing the amount of 26Al in the bone of the 2 rats, the uremic animal was found to have more than twice that found in the bone of the normal rat when expressed either per g dry or wet weight of bone. However, 26Al content of other tissues was similar in the 2 animals. This suggests that uremic bone may have a greater affinity for aluminum than normal bone, but kidney, liver, brain, heart, and muscle appear to behave similarly in uremic and normal rats in regard to incorporation of a single trace dose of isotope in the 3-week time frame of the present study. PMID- 7867247 TI - The rectal carriage of yeast in patients with vaginal candidiasis. AB - Reinfection from the lower gastrointestinal tract is a possible source of recurrent vulvo-vaginal candidiasis. A prospective study to assess the prevalence of yeast carriage in various orifices (including the rectum) in controls and patients, and the relationship to acute vaginitis, was conducted. Cultures for yeast were obtained from the mouth, rectum, vulva, and vagina every 1-2 months for 1 y from the patients. The prevalence of yeast carriage in healthy controls was 3/37 (8.1%) from the vulva, vagina, and rectum, and 4/37 (10.8%) from the mouth. In patients, yeast carriage during episodes of vaginitis was: from the vagina, 190/193 (98.4%); from the vulva, 107/193 (55.4%); from the rectum, 93/193 (48.2%); and from the mouth, 52/193 (26.9%). During visits without vaginitis, yeast carriage was lower: in the rectum, 59/587 (10.1%); in the vulva, 53/459 (11.6%); in the vagina, 77/587 (13.1%); and in the mouth, 89/587 (15.2%). Yeast in the lower bowel during symptomatic vaginitis is higher (p = 0.0001) than in controls, but not significantly greater during asymptomatic periods. Recurrence of Candida vaginitis is not dependent on yeast reservoir in the lower gut between symptomatic episodes. PMID- 7867248 TI - Five-year changes in airflow obstruction and airway responsiveness in mild to moderate asthma. AB - We documented changes in airflow obstruction and airway responsiveness to histamine after a period of 5 +/- 1 y in 40 subjects with mild to moderate asthma, 14 men and 26 women, aged 20-68 y (mean: 43.6 y). Asthma had to be stable at both evaluations. Each subject answered a respiratory questionnaire and expiratory flows and airway responsiveness to histamine were measured. No significant difference was found between the sub-groups based on atopic status and medication use for mean 5-y changes in FEV1 or PC20. However, although severity of asthma was similar in both groups, the number of subjects who significantly increased their FEV1 or PC20 at 5 y tended to be higher in the group using corticosteroids regularly (> 9 months/y): FEV1: 35.7%, PC20: 42.9% compared to those using them intermittently (< 3 months/y): FEV1: 23.3%, PC20: 35.3% (p > 0.05). This difference was related to recent (< 6 months) use of inhaled corticosteroids. On the other hand, the number of subjects with a significant reduction in FEV1 or PC20 after 5 y was lower when inhaled corticosteroids were used regularly: FEV1: 14.3%; PC20: 28.6%, compared to intermittently: FEV1: 41.2%; PC20: 41.2%, although this difference was not statistically significant. Changes in FEV1 or PC20 at 5 y were not correlated with the duration of asthma, the number of months on inhaled corticosteroids, or age at the time of diagnosis. Airway responsiveness was most often improved in atopics compared to non-atopics. In conclusion, overall 5-y changes in FEV1 or PC20 in our group of subjects were minimally influenced by the duration of the asthma and age at the time of diagnosis. The number of subjects with improved airway responsiveness was higher among atopics and after regular use of inhaled corticosteroids. Further prospective studies should be done on the long-term influence of regular vs. intermittent use of inhaled corticosteroids on the natural history of asthma. PMID- 7867249 TI - A cross-sectional seroepidemiologic survey of chronic hepatitis B virus infections in Southeast Asian immigrants residing in a Canadian urban centre. AB - To document the number of individuals who might qualify for interferon therapy and what impact the costs of treatment will have on the health care system, the serologic and biochemical profiles of 140 hepatitis B surface antigen (HBsAg) positive individuals of Asian descent (72 Vietnamese, 69 Chinese) were evaluated with respect to their hepatitis B e antigen (HBeAg) status and biochemical parameters (ALT, bilirubin, and prothrombin time). The mean +/- SD age of the study population was 33.5 +/- 13.4 y. Eighty-six (61%) were male. The HBeAg was positive in 64 (46%) of cases (41% of Vietnamese and 51% of Chinese) with no apparent sexual predilection. The ALT values exceeded 1.5 x normal in 23/64 (36%) cases. Mean serum bilirubin and prothrombin times were within normal limits. The results of this study demonstrate that approximately 50% of HBsAg positive immigrants from Southeast Asia are also HBeAg positive, and 36% of these individuals have elevated ALT values (> 1.5 x normal). Thus, according to estimated carrier rates and present guidelines for treatment, approximately 1-2% of the total Southeast Asian immigrant population are candidates for interferon therapy. With an immigrant population of approximately 900,000 and a cost of $6,500/patient, the total cost to the Canadian health care system will approach $100 million, or 1.3% of the present health care budget. These results underscore the need for a reappraisal of present treatment guidelines and implementation of universal vaccination in this country. PMID- 7867250 TI - Does saline "correct" the abnormal mass balance in metabolic alkalosis associated with chloride depletion in the rat? AB - An elevated plasma pH and bicarbonate are the clinical hallmarks of metabolic alkalosis. Nevertheless, to fully define its pathophysiology, one needs a quantitative interpretation of events in 3 areas - the ECF, ICF, and urine. Accordingly, our purpose was to study mass balance in Cl--depletion metabolic alkalosis with normal initial balance for Na+ and K+. In the 20 h following the "exchange" of Cl- (loss, 2455 mumol) and HCO(3-) (gain, 2455 mumol), only 334 mumol HCO(3-) remained in the ECF and 337 mumol were excreted. The remaining 1784 mumol disappeared primarily via titration because 3051 mueq of endogenous anions were produced and excreted largely with K+. Accordingly, metabolic alkalosis was associated with a deficit rather than a surplus of HCO(3-). To reflect the shift of H+ into cells driven by the exit of K+, the cumulative deficit of Cl- was replaced as KCl or NaCl. The fall in plasma [HCO(3-)] was larger in the KCl group (13.2 vs. 9.4 mmol/L); it was largely due to H+ exit from cells; in contrast, disappearance of HCO(3-) from the ECF was due to new endogenous acid production in the NaCl group. Thus, there was an overall deficit of HCO(3-) in metabolic alkalosis associated with KCl depletion (extracellular alkalosis and intracellular acidosis); processes in the ICF were not corrected by NaCl. PMID- 7867251 TI - Hemoglobinopathies: three illustrative case studies. AB - Three cases studies from the Regional Hemoglobinopathy Laboratory at St. Joseph's Hospital in Hamilton are presented. These cases demonstrate the diagnostic value of a comprehensive hemoglobinopathy screen, family studies, and appropriate clinical information in solving complex hemoglobinopathy problems. The first case is a 79-year-old woman found to have small amounts of an unknown hemoglobin migrating electrophoretically in the position of hemoglobin S. The second case describes a boy of Greek extraction with a thalassemic blood picture but otherwise normal hemoglobinopathy screen. The third case involves a 70-year-old man with a previously normal hemoglobinopathy screen who subsequently showed evidence of alpha thalassemia. PMID- 7867252 TI - Clinical epidemiology in chronic uremia. AB - The burden of disease in end-stage renal disease (ESRD) is high. The cost of end stage renal disease therapy is also high. The age and co-morbidity of patients is increasing, and many patients are started on therapy with little hope of rehabilitation, and with a high likelihood of death within a short period of time. Data from large prospective studies are necessary to help patients and doctors to make decisions concerning the initiation and cessation of dialysis. Inadequate dialysis and malnutrition may adversely influence clinical outcome, and cardiovascular disease exerts a large influence on morbidity and mortality. Clinical trials are necessary concerning the effect on clinical outcome of dialysis prescription, interventions to improve malnutrition, hypertension, anemia, hyperparathyroidism, hyperlipoproteinemia, and diabetes mellitus. PMID- 7867253 TI - Molecular genetics of inherited eye disorders. AB - In the past 10 y, there have been considerable advances in the mapping, isolation, and characterization of many genes for important ocular conditions: retinitis pigmentosa, Norrie disease, Waardenburg syndrome, choroideremia, aniridia, retinoblastoma, and others. The candidate gene approach has now supplemented classical linkage studies and positional cloning in the investigation of ocular disorders. Developmentally expressed genes and animal models have provided insights as to the etiology of other disorders. With this knowledge at hand, genetic counselling for heritable eye diseases has been greatly improved. PMID- 7867254 TI - The principles of gene therapy in Duchenne muscular dystrophy. AB - Somatic cell gene therapy (GT) for genetic disease such as Duchenne muscular dystrophy entails the introduction of normal, or at least functionally adequate, alleles of a gene into target cells for correction or mitigation of deleterious consequences of the disease's characteristic mutation. The following factors have a major impact upon the efficiency of GT: the artificial gene construct, the promoter, the delivery system, and the mode of dissemination of the therapeutic genes. For skeletal muscles, replication-defective adenovirus represents an efficient delivery system, but only if immature muscle cells are abundant in the muscle. The major drawback of adenoviruses is that the maximal insert capacity is only about 7.5 kb, which is only sufficient to accommodate a dystrophin minigene (6.3 kb) with a constitutive promoter. These and many other problems still require solution in experimental animals before single-muscle pilot studies of GT can be undertaken for such human muscle diseases as Duchenne muscular dystrophy. PMID- 7867255 TI - Phenylketonuria revisited. AB - This article describes the parts played by Bickel, Hickmans, Gerrard, and Woolf in the preparation of a formula low in phenylanine and in the treatment of the first child with phenylketonuria (PKU) with a low phenylalanine diet. As the child whom they were treating was 2 years old, and was already appreciably retarded mentally, the apparent improvement in her mental status was ascribed, by their medical colleagues, to the extra attention that the child was receiving and not to the biochemical changes noted in her blood. PMID- 7867256 TI - Complications of day-case angiography using 5F catheters. AB - Questionnaires were sent retrospectively to patients who had undergone day-case angiography at a British teaching hospital to evaluate the complications suffered after leaving hospital. In 1992, 5F catheters were used in 61 day-case patients. On analysis of the responses and detailed follow-up in areas of concern, no unexpected complication was found. It is concluded that day-case angiography using 5F catheters is associated with low morbidity after discharge home. PMID- 7867257 TI - A potential pitfall in bronchial artery embolization. AB - Two cases of patients with massive haemoptysis undergoing bronchial arteriography are described. Both had collateral vessels which filled the right subclavian artery from the right intercosto-bronchial trunk. Such vessels form a potential route for the passage of embolic material into the subclavian artery and its branches during therapeutic bronchial artery embolization. To avoid this potential complication, super selective catheterization with the positioning of the catheter tip well into the bronchial artery beyond the origin of the intercostal artery and any large collateral vessels is recommended. PMID- 7867258 TI - Variation in portal and hepatic venous anatomy as shown by magnetic resonance imaging: implication for transjugular intrahepatic portosystemic shunt. AB - Magnetic resonance imaging (MRI) is able to show the portal and hepatic venous anatomy. Variation in the relative position of the right portal vein and the right hepatic vein is shown in three parasagittal planes in three different cases and accounts for the different appearances of the transjugular intrahepatic portosystemic shunt (TIPS) in three patients. MRI shows that the optimal plane of exit from the right portal vein is 1-2.5 cm from the lateral wall of the inferior vena cava but individual variation does occur: a right portal vein with a more anterior and craniad location may not be accessible to the Colapinto needle; a parenchymal tract which is directed too far inferomedially risks puncturing the portal vein outside the liver capsule. PMID- 7867259 TI - The significance of ipsilateral leg ischaemia after renal transplantation. AB - We present three renal transplant patients who have been investigated for leg ischaemia on the side of the transplant. All were men aged between 50 and 57 years. Two had an iliac stenosis proximal to the transplant kidney and were treated successfully by percutaneous transluminal angioplasty. The other, with an internal iliac anastomosis, had occlusion of the external iliac artery and underwent femoro-femoral bypass grafting. Eight years later, almost 17 years after transplantation, this hyperlipidaemic patient was found to have an internal iliac origin stenosis proximal to the transplant kidney and also underwent successful angioplasty. In patients with functioning renal transplants, symptoms of arterial insufficiency in the ipsilateral leg should be investigated urgently because a proximal iliac stenosis potentially threatens graft survival. PMID- 7867260 TI - Childhood ossification of the anterior longitudinal ligament of the cervical spine. AB - Two paediatric cases of acquired ossification of the cervical anterior longitudinal ligament are described. This has not been previously reported in childhood. The first was associated with corrosive ingestion requiring oesophagectomy and colonic interposition and the second with acute lymphoblastic leukaemia initially presenting as idiopathic hypereosinophilic syndrome. Possible mechanisms are discussed. PMID- 7867261 TI - Cerebrotendinous xanthomatosis in two sisters: case reports and MR imaging. AB - Cerebrotendinous xanthomatosis is a rare inherited disorder of bile acid metabolism producing xanthomata and severe, progressive neurological deficits. In spite of the rarity of the condition it is important because it is treatable: the neurological deterioration can be halted and in some cases reversed. PMID- 7867262 TI - Technical report: ultrasound guidance for injection of soft tissue lesions around the heel in chronic inflammatory arthritis. AB - We describe the use of ultrasound guidance for local steroid injection of the retrocalcaneal bursa and the tibialis posterior tendon sheath in patients with chronic inflammatory arthropathy. Ultrasound guidance may be the injection technique of choice but is particularly indicated for patients with lesions unresponsive to injections guided by palpation. PMID- 7867263 TI - Case report: intravenous leiomyomatosis, an unusual cause of intracardiac filling defect. AB - Intravenous leiomyomatosis (IVLM) is a condition characterized by intravenous growth of histologically benign smooth muscle tumour originating in the uterus. Rarely, the tumour can extend via the inferior vena cava into the right side of the heart. In only one previously described case has the tumour extended into the pulmonary artery. We present a second such tumour. In this case, tumour calcification could be identified during cine recording moving within the pulmonary outflow tract, a finding not commonly associated with this condition. The radiological investigation of IVLM is briefly discussed. PMID- 7867264 TI - Case report: the diagnostic value of contrast-enhanced computed tomography in acute bilateral renal cortical necrosis. AB - Acute bilateral renal cortical necrosis is a relatively rare cause of acute renal failure accounting for only 2% of cases in the Western World. The pathophysiology of this condition is complex, but ultimately leads to the destruction of the renal cortex with sparing of the renal medulla. A definitive diagnosis is based on renal histology. In this report we describe a patient in whom this diagnosis was made using contrast-enhanced computed tomography as renal biopsy was contraindicated. PMID- 7867265 TI - Case report: neonatal adrenal haemorrhage presenting as an acute right scrotal swelling (haematoma)--value of ultrasound. AB - Acute scrotal swelling resulting from remote intra-abdominal pathology is a well recognized but rare entity. The present report relates to such a case in a neonate who presented with an acute right scrotal haematoma, adrenal haemorrhage not being suspected clinically, but detected ultrasonographically. In the imaging of neonatal scrotal swellings, abdominal ultrasound is important in excluding a primary intra-abdominal event. PMID- 7867266 TI - Case report: paratesticular rhabdomyosarcoma--colour Doppler appearances. AB - Paratesticular rhabdomyosarcoma is a rare tumour of childhood and early adult life. We report a case in which the paratesticular location and colour Doppler appearances led to confusion with epididymitis. PMID- 7867267 TI - Fractures of Acromion. PMID- 7867268 TI - The small bowel follow-through: time to sit up. PMID- 7867269 TI - Use of ultrasound in positioning a catheter for thrombolysis of an occluded prosthetic femoropopliteal graft. PMID- 7867270 TI - Use of ultrasound in positioning a catheter for thrombolysis of an occluded prosthetic femoropopliteal graft. PMID- 7867271 TI - Nuclear medicine: radiologists must love it or leave it. PMID- 7867272 TI - The potential value of magnetic resonance imaging in infertility. AB - The potential value of magnetic resonance imaging as a diagnostic tool in infertility was investigated. Twenty-six women with primary or secondary infertility and symptoms of dysmenorrhoea or menorrhagia were studied prospectively using conventional T1- and T2-weighted spin-echo techniques. Positive diagnoses were obtained in 20 of 26 (76.9%) patients. Of these, 18 (69.2%) had lesions likely to be significantly contributing to infertility. Adenomyosis was detected in 14 patients (53.8%) with 11 showing the diffuse pattern while three had discrete adenomyomas. Cystic lesions typical of endometriosis were detected in seven patients (26.9%), four of these also had evidence of adenomyosis. The endometriotic lesions were also seen at laparoscopy in each case. Five patients (19.2%) had leiomyomas, one in a patient with adenomyosis and endometriosis and one in a patient with endometriosis alone. Only one patient had submucous leiomyomas causing significant distortion of the endometrial mucosa likely to affect fertility. Magnetic resonance imaging is valuable in the investigation of unexplained infertility where it provides a high diagnostic yield particularly if uterine pathology is suspected. PMID- 7867273 TI - The value of MRI in the assessment of traumatic intra-uterine adhesions (Asherman's syndrome). AB - Since the publication titled Amenorrhea Traumatica (atretica) by Asherman in 1948, this syndrome has been considered a well defined clinical entity. It is typically manifested by the formation of fibrous adhesions involving the uterine cavity, sometimes involving the internal cervical os. The major causes are surgical intervention of the post-partum uterus and elective termination of early pregnancy. The diagnosis is usually suggested by hysterography and confirmed by hysteroscopy. The MRI appearances are reported in four cases of Asherman's Syndrome in which the diagnosis was confirmed by hysteroscopy. The full range of MRI appearances in Asherman's Syndrome has not been established and to our knowledge there has been only one case reported in the literature. PMID- 7867274 TI - Magnetic resonance scanning in cystic fibrosis: comparison with computed tomography. AB - Comparison has been made between two different spin-echo sequence MR scans and CT scans of the lungs in 17 patients with cystic fibrosis. Scans were assessed for bronchial dilation, bronchial wall thickening and mucus plugging. The resolution of MR does not, at present, compare with CT. TE7 ms matched with CT for demonstrating the extent of bronchiectasis whereas TE30 ms scans were inferior to CT. Stronger background lung signal and less artefact was seen on TE7 ms scans compared with TE30 ms scans. MR is a developing technology that does not involve ionizing radiation which, with further refinement, may prove to be useful in imaging lung pathology in cystic fibrosis. PMID- 7867275 TI - Lymphatic filling in arthrography following total hip replacement. AB - The significance of lymphatic filling at hip arthrography on prosthetic hips is uncertain. Clearly if lymphatic opacification has a direct relationship to loosening, this could lead to increased surgical exploration. Ninety-one patients were studied to determine whether opacification of lymphatics during hip arthrography correlated with loosening of the prosthetic hip. Plain radiographs were evaluated and a total of 92 hip arthrograms were assessed retrospectively. Radiological evidence of prosthetic loosening at hip arthrography was present in 61 patients. Fifty-three patients subsequently had surgical exploration and 50 were confirmed to have loose and/or infected components. In only 18 of these patients had lymphatic filling been demonstrated at arthrography. No evidence of loosening was seen in 23 patients; however, lymphatic opacification occurred in 10 of these arthrograms. This study does not demonstrate any correlation between prosthetic loosening, either with or without infection, and filling of the nearby lymphatic vessels. This finding contradicts an earlier report in the literature. PMID- 7867276 TI - Comparison of ultrasound with fluoroscopy in the assessment of suspected hemidiaphragmatic movement abnormality. AB - A comparative study of quantitative hemidiaphragmatic ultrasound with fluoroscopy was undertaken in 30 patients referred for investigation of suspected hemidiaphragmatic movement abnormality. The aim of this study was to determine whether assessment with ultrasound or fluoroscopy differed, and which technique appeared more suitable in the investigation of hemidiaphragmatic movement disorder. There were four technical failures using fluoroscopy (13%), compared with none using ultrasound. Using the normal ranges of right to left ratio of maximal excursion (0.5-2.0 for fluoroscopy and 0.5-1.6 for ultrasound) there was concordance in 21 out of 26 (81%) patients. All cases of abnormality on fluoroscopy were seen on ultrasound. Four of the discordant cases had excursions on the lesser side in the normal range on ultrasound suggesting a milder movement abnormality detected by ultrasound than by fluoroscopy. Sniff testing conferred no advantage over quantitative testing. Ultrasound has technical, qualitative and quantitative advantages over fluoroscopy and should be the method of choice in the investigation of suspected hemidiaphragmatic movement abnormality. PMID- 7867277 TI - Ultrasound demonstration of lymph nodes in the hepatoduodenal ligament ('Daisy Chain nodes') in normal subjects. AB - We describe the ultrasound appearances of lymph nodes in the hepatoduodenal ligament ('Daisy Chain Nodes') in normal subjects. Nodes were identified in 69 of 116 patients referred for abdominal ultrasound, who had no underlying reason for lymphadenopathy. Patients with primary malignancy or inflammatory pathologies were excluded from the sample. In 26 patients, the hepatoduodenal ligament (HDL) was not visualized. Therefore Daisy Chain nodes were visualized in 77% of patients where the HDL was visualized. Nodes were seen more frequently in younger patients; this was attributed to more homogeneous hyperechoic perinodal fat in the younger age group and the larger size of nodes in young patients. Study of normal lymph nodes will help to determine criteria for the appearances of pathological nodes in the abdomen. PMID- 7867278 TI - Central control of ventilation in neuromuscular disease. AB - Neuromuscular diseases cause many changes that affect ventilation and ventilatory control. The pattern of ventilation may become abnormal because of muscle disease. Muscle fatigue and discordant breathing can lead to hypoventilation and CO2 retention. Motoneuron destructive and demyelinating disorders inevitably lead to hypoventilation and hypercapnia. Changes in chest wall mechanics can lead to changes in level of ventilation and ventilatory drive. In many neuromuscular disorders, ventilatory response to CO2 is depressed, but this does not imply an abnormal central control mechanism in all instances. Many patients with neuromuscular diseases have a normal ventilatory drive as manifested by a normal P0.1 but have low ventilation because of abnormalities in muscle function and neuromuscular transmission. Central drive is diminished in some patients with neuromuscular disease but not in the majority of cases. Hypoventilation during sleep is a common problem in neuromuscular diseases. Thus, a combination of factors can lead to abnormal patterns of breathing and hypoventilation in these disorders; no single pathophysiologic mechanism can explain all the abnormalities. Clinically, it is important to appreciate the prevalence of ventilatory control disorders and include appropriate evaluations when assessing patients with neuromuscular diseases and offering therapeutic options. PMID- 7867279 TI - An overview of respiratory muscle function. AB - This article reviews the important features of respiratory muscle structure and function, including fiber types, fatigue, work and efficiency of breathing, neural connections, circulation, and mechanical properties. Emphasis is placed on the functional anatomy and the coordination and interaction of respiratory muscle action. Normal function is contrasted with the respiratory muscle dysfunction seen in patients with neuromuscular disease. PMID- 7867280 TI - Physiological effects of diaphragm muscle denervation and disuse. AB - From our studies, it is clear that diaphragm muscle neuromotor control is responsive to alterations in innervation and activation. These adaptations to altered use appear to be most pronounced among fast-twitch motor units composed of type II muscle fibers. Because the plasticity involves diminished contractile strength and a slowing of shortening velocity, it might be considered maladaptive with respect to diaphragm functional demands; however, because ventilatory behaviors of the diaphragm most likely require the recruitment of only type S motor units (type I muscle fibers) that appear to be less adaptive, the functional decrements following disuse may involve only nonventilatory behaviors that require the recruitment of fast-twitch (type II muscle fibers) motor units. In other words, in many circumstances, diaphragm muscle adaptations may reduce the functional reserve capacity of the muscle without affecting normal ventilatory performance. The extent to which these observations can be applied to humans remains speculative. Certainly, the animal models approximate the human condition in that ventilatory requirements of the diaphragm are comparable across mammalian species. It is known that type II fibers comprise approximately 60% of the human diaphragm. Therefore, type II muscle fibers in humans may also be particularly vulnerable to adaptive changes associated with diaphragm disuse. With regard to the functional decrements that might ensue in humans, we have estimated that the forces generated by the human diaphragm during tidal breathing are approximately 10% of maximum. Therefore, as in other species, ventilatory forces generated by the diaphragm in humans most likely do not require the recruitment of fast-twitch (type II) motor units. Normal ventilatory behaviors may therefore be spared from maladaptive changes in diaphragm performance. With the imposition of mechanical loads to breathing associated with certain chronic pulmonary diseases, however, it might be expected that the recruitment of fast twitch motor units would be required on a more continuous basis. Such diseases are normally progressive and incremental, therefore allowing sufficient time for adaptation. One adaptation that might be expected would be an overall improvement in the fatigue resistance of fast-twitch motor units. This adaptation could be accomplished by altering the metabolic enzyme activities of type II muscle fibers, by affecting the expression of contractile proteins, or both. Improvement of muscle fiber fatigue resistance is usually at the expense of fibre size, contractile strength, or both.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7867281 TI - Respiratory dysfunction in muscular dystrophy and other myopathies. AB - Respiratory muscle weakness occurs in a wide spectrum of acute and chronic myopathic disorders, and may cause a restrictive ventilatory defect and life threatening ventilatory failure. Therapeutic intervention is based on a thorough knowledge of the course of each disease and meticulous monitoring of respiratory function. Comprehensive management of patients with myopathic disorders requires an understanding of the pathophysiology and specific manifestations of respiratory involvement in each disease. PMID- 7867282 TI - Respiratory dysfunction in amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the voluntary motor system. Involvement of the respiratory system is inevitable and leads to the development of respiratory failure, the usual cause of death in this disorder. ALS at present is incurable, and only symptomatic treatment is available. This article presents guidelines for the recognition and management of respiratory failure. PMID- 7867283 TI - Respiratory dysfunction in myasthenia gravis. AB - Myasthenia gravis can affect the respiratory system, causing respiratory muscle weakness, an abnormal breathing pattern, and blunted ventilatory responses. Specific treatment can reverse most of these effects and prevent the development of respiratory failure. PMID- 7867284 TI - Ventilatory dysfunction in multiple sclerosis. AB - Multiple sclerosis (MS) can produce a variety of different respiratory abnormalities because of the multi-focal nature of central nervous system involvement in the disease. This article reviews the different patterns of respiratory involvement in MS and correlates them with the known neuroanatomy of respiratory control. Methods of monitoring pulmonary function in MS are explored, and the treatment of acute ventilatory failure in MS is discussed. PMID- 7867285 TI - Respiratory dysfunction in Guillain-Barre syndrome. AB - Guillain-Barre syndrome (GBS) is the most common cause of acute paralysis and neuromuscular ventilatory failure. Although treatment with plasma exchange and immune globulins has decreased the duration of mechanical ventilation by half, 10% to 30% of patients require mechanical ventilation, 5% to 10% remain seriously disabled, and 3% to 8% die as a result of largely avoidable complications. Good clinical outcome depends to a large extent on the anticipation and management of ventilatory failure and its complications. PMID- 7867286 TI - Respiratory dysfunction in Parkinson's disease. AB - The parkinsonian syndromes include idiopathic Parkinson's disease, parkinsonian syndromes secondary to several known causative agents, and parkinsonian syndromes associated with more widespread CNS lesions and extensive neurologic deficits. They constitute movement disorders with a similar constellation of symptoms: rigidity, tremor, bradykinesia, gait impairment, and postural instability. All of the parkinsonian syndromes are associated with excess morbidity and mortality from respiratory causes, and all can produce the pattern of pulmonary function impairment consistent with neuromuscular disease. In addition, the parkinsonian syndromes can produce upper airway obstruction and abnormalities of ventilatory control, both of which can be life-threatening in those with MSA. The medications used to treat these disorders can also produce respiratory disease. A syndrome of L-dopa-induced respiratory dysfunction has been described, which may be a heterogeneic disorder of choreiform movements of the respiratory muscles, rigidity-akinesis of the respiratory muscles, or abnormal central control of ventilation, all related to the drug. In addition, the ergot-derived dopamine agonists can cause pleural and pulmonary fibrosis. PMID- 7867287 TI - Respiratory dysfunction in stroke. AB - Respiratory function depends on numerous neurologic structures, the organization of which extends from the cerebral cortex to the medulla. The study of patients who have had strokes has allowed deductions about this organization, and various neurologic pathways have been increasingly recognized. The voluntary pathway travels with the corticospinal motor tract. It is typically damaged in the "locked-in" syndrome and leads to normal automatic breathing that cannot be voluntarily altered. The automatic pathway takes its origin in the lower brainstem and is damaged mainly in lateral medullary strokes. Even a unilateral lesion here may lead to complete failure of respiration and result in death during sleep (Ondine's curse). The preservation of the limbically induced fluctuations of respiration in automatic breathing suggests a third pathway that may share its distal extent with the automatic pathway. Respiratory dysfunctions may also provide useful information regarding the cause and prognosis of stroke. PMID- 7867288 TI - Respiratory dysfunction associated with traumatic injury to the central nervous system. AB - Pulmonary dysfunction is a common complication of head trauma and spinal cord injury. Abnormal breathing patterns reflect the influence of altered neural integration. Early arterial hypoxemia can result from ventilation-perfusion mismatching, microatelectasis, aspiration, fat embolism, or the development of the adult respiratory distress syndrome. Significant changes in lung volumes, ventilation, and gas exchange can occur in spinal cord injury as a result of the loss of diaphramatic or intercostal muscle function. Recruitment of accessory respiratory muscles plays an important role in stabilizing the rib cage and improving expiratory function. Strength training improves expiratory muscle function in quadriplegics and should be continued indefinitely. Most importantly, survival of patients with CNS injuries improves with meticulous and vigorous pulmonary hygiene. The pulmonary hygiene program should include regular changes in the patient's position, assisted coughing and deep breathing exercises, incentive spirometer, bronchodilators, fiberoptic bronchoscopy when indicated, and frequent monitoring of pulmonary mechanics. Long-term survival of the patient with head trauma or spinal cord injury is correlated to successful weaning from mechanical ventilation. Various forms of mechanical ventilator support can be adopted for the patient's ventilatory needs, and many patients will achieve some degree of freedom from mechanical ventilation. Newer ventilatory assist devices that do not require tracheostomy should be considered. PMID- 7867289 TI - Assessment of ventilatory function in patients with neuromuscular disease. AB - In early phases of neuromuscular disease, patients are either free of respiratory symptoms or have exertional dyspnea not explained by obvious obstructive or restrictive lung disease. Physical examination may be negative because generalized muscle weakness does not correlate with the degree of respiratory muscle involvement. When the diaphragm is involved, one may detect the absence of outward excursion during inspiration or even paradoxic inward inspiratory movement of the abdomen on one side. A substantial loss of respiratory muscle strength is typically accompanied by little or no change in spirometry or arterial blood gas composition. Other characteristics are moderate loss of maximal voluntary ventilation and an increase in residual volume, yet PImax and PEmax may be as low as 50% of the predicted value. In more advanced neuromuscular disease, patients may have severe symptoms if the onset is acute or subacute; however, patients with chronic advanced generalized muscle weakness do not exercise and, therefore, may not be breathless. Many patients with advanced neuromuscular disease present with daytime somnolence as a manifestation of a sleep-related breathing disorder. Physical examination may reveal generalized muscle weakness and difficulty with speech or swallowing. Signs specific to respiratory involvement include tachypnea, use of neck inspiratory muscles and abdominal expiratory muscles, and loss of chest-abdomen synchrony. Sometimes paradoxic bilateral inward movement of the abdomen with inspiration is overt. Patients may be unable to cough effectively, have scoliosis, and lack a gag reflex. At this advanced stage, PImax and PEmax are lower than 50% of the predicted value, and the vital capacity is reduced. Maximal voluntary ventilation increases, and residual volume increases further. Patients may not yet exhibit CO2 retention during the day and may even have a low PaCO3. A sleep study may reveal significant hypopneas with severe desaturation and hypercapnia, especially during REM sleep. It is important to be aware that overt ventilatory failure can occur abruptly and that measurement of arterial blood gas composition is not a reliable indicator of this danger. Therefore, it is critically important to heed clinical phenomena, such as increasing dyspnea and tachypnea, and symptoms of sleep disturbance, such as morning headache and daytime somnolence. Physicians should make serial measurements of VC and respiratory muscle strength in patients considered to be at risk for further deterioration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7867290 TI - Options for mechanical ventilation in neuromuscular diseases. AB - A variety of mechanical devices may be used to provide assistance when ventilation and cough are severely impaired by progressive respiratory weakness caused by neuromuscular disease. Traditionally, positive pressure ventilation via a tracheostomy has been used, but if upper airway function is adequate, a variety of noninvasive devices also may be considered. Although positive pressure ventilation is the preferred noninvasive mode for assisting ventilation, other modes may be selected depending on patient needs, preferences, and physical characteristics. PMID- 7867291 TI - Long-term care, rehabilitation, and legal and ethical considerations in the management of neuromuscular disease with respiratory dysfunction. AB - Neuromuscular disease, while for the most part progressive, allows for ample time to discuss options for long-term care. Frank discussions among clinicians, the patient, and family will allow for an ethical decision process. With the clinician's awareness of the inherent difficulties in judging life satisfaction, an early discussion of first noninvasive measures, then tracheostomy with positive pressure ventilation, will allow for a rational, moral, and continuing treatment plan. The early introduction of rehabilitation techniques should allow for maximal time in the home setting where life satisfaction may be enhanced. As the disease progresses, the issues such as ventilator withdrawal or even the decision not to initiate invasive ventilation need to be addressed. The better our understanding, through continuing study of NMD, of the instances when the use of continued technology will enhance life, will support ethical discussions, guide clinicians and patients, and help shape a national health-care agenda. PMID- 7867292 TI - Comparison of TechLab Clostridium difficile Tox-A enzyme immunoassay and Bartels Prima system toxin-A EIA. AB - We evaluated the Bartles Clostridium difficile toxin A test and the TechLab Tox-A test to detect C. difficile toxin A in stool. The results were compared with C. difficile cytotoxicity assays. Of the 463 specimens tested 82 (17.7%) tested positive by cytotoxicity assay. The sensitivity, specificity, and positive and negative predictive values of the TechLab EIA were 86.6%, 93.7%, 74.7%, and 97.0%, respectively. For the Bartels Prima EIA, sensitivity, specificity, and positive and negative predictive values were 95.1%, 95.5%, 82.1%, and 98.9%, respectively. The differences in sensitivity were statistically significant. Indeterminate results requiring repeat testing were more common with the TechLab EIA than with the Bartels Prima EIA. Of the two kits, the Bartels EIA is preferable, primarily because of its increased sensitivity. PMID- 7867293 TI - Detection of human cytomegalovirus in peripheral blood leukocytes by the polymerase chain reaction and a nonradioactive probe. AB - This study evaluated the effectiveness of polymerase chain reaction (PCR) combined with a nonradioactive probe for the early detection of cytomegalovirus (CMV) in buffy-coat specimens of immunocompromised patients. Dot-blot hybridization with a digoxigenin-labeled probe was used to detect a 262-bp PCR amplified fragment of the major immediate-early gene of CMV DNA. The results were compared with tissue cultures isolation of CMV. The study included 172 buffy-coat specimens from 72 immunocompromised patients. All 28 buffy-coat specimens positive by culture were also positive by PCR. The remaining 144 specimens were negative by culture; however, 47 of these were positive by PCR. Consequently, PCR was in agreement with culture results in 72% of the samples. Of the 47 PCR positive-culture-negative specimens, 23 were from patients who had positive buffy coat cultures at other times during their treatment. Chart review showed that an additional 16 of the PCR-positive-culture-negative samples were from patients with clinical evidence of active CMV disease. The eight remaining specimens were from five patients without signs of active disease. Specimens from 11 healthy volunteers were negative by PCR. In this study PCR was shown to be more sensitive than culture because it allowed earlier detection of viremia and demonstrated CMV in buffy-coat specimens that were negative by culture. PMID- 7867294 TI - Assessment of the bactericidal activity of sparfloxacin, ofloxacin, levofloxacin, and other fluoroquinolones compared with selected agents of proven efficacy against Listeria monocytogenes. AB - The search for alternative therapeutic agents for listeriosis includes the quinolone group. Accordingly, the bactericidal activity of ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin, sparfloxacin, and temofloxacin, in comparison with that of ampicillin and sulfamethoxazole-trimethoprim, was evaluated against Listeria monocytogenes at 24 and 48 h of incubation using time kill kinetic methodology. The inhibitory concentrations for each agent fell into a narrow range comparable with ampicillin. For example, the minimum inhibitory concentration (MIC) ranges, MIC90 (24 h), and MIC90 (48 h) of the most active quinolone, sparfloxacin, were 0.25-2, 2, and 2 micrograms/ml, respectively, with 4 micrograms/ml achieving > or = 99.9% killing of the inoculum at 24 h with no regrowth by 48 h. At 2-4 times the MIC, bactericidal activity for all quinolones tested was noted at 24 h, unlike the action of ampicillin, which only becomes bactericidal at 48 h. These concentrations are within the achievable range of serum concentrations for a number of these agents. Because selected new fluoroquinolones at two to four times the MIC show bactericidal activity at 24 h, these agents may prove useful as therapeutic alternatives for the treatment of listeriosis. PMID- 7867295 TI - Comparative in vitro activity of FK-037, a new cephalosporin antibiotic. AB - The in vitro activity of FK-037, a novel parenteral oxime-type cephalosporin, was compared with that of cefepime, cefpirome, ceftazidime, imipenem, and gentamicin against a total of 668 recent clinical isolates. Minimum inhibitory concentrations were determined by a standard agar dilution procedure, and all isolates were tested at two inocula (10(4) and 10(6) colony forming units). FK 037 inhibited 90% of isolates of Escherichia coli, Klebsiella species, Proteus mirabilis, P. vulgaris, Morganella morganii, Serratia marcescens, Providencia stuartii, Citrobacter freundii, Salmonella typhi, Shigella sonnei, Yersinia enterocolitica, Aeromonas species, and Haemophilus influenzae at < or = 1 microgram/ml. FK-037 was less active against Enterobacter species, Acinetobacter species, and Pseudomonas species, requiring 16 micrograms/ml to inhibit 90% of isolates, and was inactive against Xanthomonas maltophilia. FK-037 inhibited 90% of methicillin-susceptible Staphylococcus aureus at < or = 1 microgram/ml and 90% of methicillin-resistant S. aureus at < or = 8 micrograms/ml. PMID- 7867296 TI - Candida cerebrospinal fluid shunt infection. Report of two new cases and review of the literature. AB - In this case report, we describe two patients with Candida shunt infection and review 22 cases from the previous literature. All of them had ventriculoperitoneal shunts, except one who had an external ventricular drain. The more outstanding predisposing factors were recent bacterial meningitis and/or neurosurgery (different from the shunt placement) and abdominal complications (intestinal perforation in three cases, and gastrostomy and lengthening of the distal catheter in one each). The clinical manifestations were hydrocephalus in 36%, fever in 31%, meningoencephalitis in 21%, and abdominal symptoms in 10%. The mean cerebrospinal fluid count was 78 cells/mm3 (with 77% lymphocytic predominance). Two patients died (9%); one of them was the only case in which the catheter was not removed. The recommended treatment is the replacement of the shunt and antifungal therapy with intravenous amphotericin B; in cases of poor clinical condition, the latter should also be given intraventricularly. PMID- 7867297 TI - An old antibiotic for a new multiple-resistant Enterococcus faecium? AB - Enterococci have become an important cause of nosocomial infections and may demonstrate high-level resistance to multiple antibiotics. We present the case of a 68-year-old man with a history of small cell lung cancer, who developed bacteremia due to a strain of Enterococcus faecium. The isolate was resistant to multiple antibiotics including vancomycin, ampicillin, aminoglycosides, quinolones, and macrolides. The patient was successfully treated with doxycycline and removal of an infected central venous catheter. PMID- 7867298 TI - DU-6859a, a new fluoroquinolone agent. Comparative in vitro activity against enteric pathogens and multiresistant outpatient Escherichia coli. AB - The activity of DU-6859a, a new fluoroquinolone antimicrobial agent, was compared with that of ciprofloxacin by agar dilution susceptibility testing against enteric pathogens and multiresistant Escherichia coli. The results indicate that DU-6859a inhibits most of these organisms at concentrations similar to those of ciprofloxacin. DU-6859a showed increased activity compared to ciprofloxacin against Campylobacter species isolates. PMID- 7867299 TI - Cefquinome (HR 111V). In vitro evaluation of a broad-spectrum cephalosporin indicated for infections in animals. AB - Cefquinome (formerly HR 111V), an aminothiazolyl cephalosporin, was compared with cefepime, cefpirome, cefotaxime, and ceftazidime against 681 clinical cultures and a challenge set of bacteria with well-characterized resistance mechanisms. Cefquinome minimum inhibitory concentrations (MIC90) for the enterobacteriaceae ranged from < or = 0.12-2 micrograms/ml with the highest MIC (4 micrograms/ml) obtained among Citrobacter freundii, Enterobacter cloacae, and Providencia stuartii strains. A total of 90% of the Pseudomonas aeruginosa were inhibited by cefquinome at < or = 8 micrograms/ml. Cefquinome activity of particular note for Gram-positive isolates included Corynebacterium jeikeium (MIC90, 8 micrograms/ml) and enterococci (MIC50, 4-8 micrograms/ml). Oxacillin-resistant Staphylococcus aureus was 32-fold less susceptible (MIC90, 16 micrograms/ml) to cefquinome than oxacillin-susceptible (MIC90, 0.5 micrograms/ml) strains. Cefquinome was very potent against fastidious isolates such as Moraxella catarrhalis (MIC90, 0.25-2 micrograms/ml); Haemophilus influenzae (MIC90, 0.06-1 micrograms/ml), Neisseria gonorrhoeae (MIC90, 0.06-0.5 micrograms/ml), and Streptococcus species (MIC90, < or = 0.03-006 micrograms/ml). When tested against organisms possessing Bush group 2 enzymes (including extended spectrum beta-lactamases), cefquinome remained active (MIC, < or = 8 micrograms/ml) against the majority of strains. This compound should be very active against pathogens generally found in animal infections and possesses a potency and spectrum comparable to the "fourth generation" cephalosporins (cefepime and cefpirome) being investigated for human infectious diseases. PMID- 7867300 TI - In vitro activity of dirithromycin, a new macrolide antibiotic, against Mycoplasma species. AB - Dirithromycin is a new macrolide antibiotic that achieves high tissue concentration. We compared its in vitro activity against Mycoplasma species with that of erythromycin and tetracycline. Clinical isolates of M. pneumoniae (40), M. hominis (40), and Ureaplasma urealyticum (40) were tested against serial dilutions of three antibiotics using a microtiter plate method. Minimum inhibitory concentrations (MIC) were read as the lowest concentration of antibiotic yielding no color change in the broth. Neither macrolide antibiotic exhibited antimicrobial activity against M. hominis; MIC50 and MIC90 for tetracycline were 0.6 and 32 micrograms/ml, respectively. MIC50 for U. urealyticum was 4.0 micrograms/ml for dirithromycin, 2.0 micrograms/ml for erythromycin, and 1.0 micrograms/ml for tetracycline. MIC90 for U. urealyticum was > 128 micrograms/ml for all three agents. Against M. pneumoniae dirithromycin exhibited MIC50 of 0.1 micrograms/ml and MIC90 of 0.1 micrograms/ml. Both values for erythromycin were 0.2 micrograms/ml; for tetracycline they were 0.1 and 1.0 micrograms/ml, respectively. These results demonstrate the high in vitro activity of dirithromycin against M. pneumoniae and suggest that this agent may have a role in the treatment of respiratory Mycoplasma infections. PMID- 7867301 TI - Postantibiotic effect of roxithromycin on streptolysin O production, hydrophobicity, and bactericidal activity of PMNL by Streptococcus pyogenes. AB - Exposure of Streptococcus pyogenes to 5 x minimum inhibitory concentration of roxithromycin for 1 h produced a significant postantibiotic effect. More than 2.5 h was necessary for roxithromycin-treated bacteria to increase by 1 log10 in colony-forming units after drug removal, compared with the unexposed cells. After exposure to and removal of the drug, treated cells failed to exhibit normal hemolytic activity for at least 4 h. The inhibitory effect persisted for 20 h after drug removal, although the extent of growth for treated and untreated cells was almost the same. Hydrophobicity of treated cells, studied throughout the logarithmic growth phase with a water-hexadecan two-phase system, was markedly decreased by 40%, compared with untreated cells 4 h after drug removal. Cells that had been treated with roxithromycin became more susceptible to the bactericidal activity of human PMNL than untreated bacteria. The data indicate that some of the metabolic activity that contributes to the virulence of S. pyogenes is affected by postexposure to roxithromycin, and its minimum inhibitory concentration and serum level might not be the best indicators of efficacy in this class of drugs. PMID- 7867302 TI - Actinobacillus (Pasteurella) ureae meningitis in a HIV-positive patient. AB - Actinobacillus (Pasteurella) ureae is a commensal of the human nasopharynx that is a rare cause of meningitis. We present an HIV-infected patient with this condition. His case, and those previously reported in the literature, implicate head trauma or a neurosurgical procedure in the pathogenesis of this condition. The patient responded to initial empiric therapy with ceftriaxone, followed by intravenous penicillin. PMID- 7867303 TI - Comparison of two enzyme immunoassays and two latex agglutination assays for detection of cytomegalovirus antibody. AB - Two commercially available enzyme immunoassays for cytomegalovirus (CMV) immunoglobulin G (IgG), Vidas and Diamedix, and two latex agglutination tests that detect both CMV IgG and IgM, CMV-Scan and CMV-Gen, were evaluated using 165 human serum specimens. Among these, 46.7% contained CMV-reactive antibody. The first three assays had sensitivities of 100%; the sensitivity of the CMV-Gen procedure was 98.7%. The specificities of the four tests were 100, 97.7, 97.3, and 93.2%, respectively. PMID- 7867304 TI - Detection of vancomycin resistance in enterococci by the Vitek AMS system. AB - The ability of the Vitek AMS system to detect vancomycin resistance in enterococci was evaluated by comparing the results to an agar dilution screen method. Of 100 strains tested, 43 were resistant and 51 were susceptible by both tests. Two strains were intermediate by Vitek but susceptible by agar screen, one was intermediate by Vitek but resistant by agar screen, and four were susceptible by Vitek but resistant by agar screen. When the Vitek intermediate and resistant results were combined, the false resistant rate was 4.4% and false susceptible rate was 8.5%. In its current format, the Vitek system appears not to have acceptable accuracy for the detection of vancomycin resistance in enterococci. PMID- 7867305 TI - Comparison of a new latex agglutination assay with indirect immunofluorescence to detect varicella-zoster antibodies. PMID- 7867306 TI - Characterization of enterococci isolated from human and nonhuman sources in Brazil. AB - A total of 330 enterococci strains isolated from several human (272 strains) and animal (27) clinical specimens and environmental sources (31) in Brazil were identified to species level. Major human sources included urine (48.5%), blood (15.8%), and wounds (9.5%). Human isolates were identified as Enterococcus faecalis (90.0%), E. faecium (6.9%), E. gallinarum (1.1%), E. durans (0.8%), E. casseliflavus (0.4%), E. raffinosus (0.4%), and E. mundtii (0.4%). Strains isolated from animals were composed of E. hirae (40.7%), E. faecalis (33.3%), E. faecium (18.5%), and E. casseliflavus (7.5%). Among environmental isolates, 42.0% were E. faecalis, 35.4% E. faecium, 13.0% E. hirae, 6.4% E. casseliflavus, and 3.2% E. durans. Antimicrobial susceptibility tests were performed for 200 strains. Overall, high-level resistance (HLR) to aminoglycosides was found in 66 (33.0%) of the strains tested. HLR to gentamicin was detected in 11.5% of the strains, whereas 19.0% of the strains showed HLR to streptomycin and 26.0% showed HLR to kanamycin. Five (22.7%) of the E. faecium strains were resistant to ampicillin [minimum inhibitory concentration (MIC) > 32 micrograms/ml]. Vancomycin MIC50 and MIC90 were 2 and 4 micrograms/ml, respectively; only eight strains (identified as E. casseliflavus or E. gallinarum) had MIC of 8 micrograms/ml. No beta-lactamase activity was detected by the nitrocefin test. PMID- 7867307 TI - Lactoferrin interaction with salmonellae potentiates antibiotic susceptibility in vitro. AB - Interaction of lactoferrin (Lf) with the cell envelope (CE) and outer membrane (OM) of Salmonella typhimurium-type strain ATCC13311 was tested by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western-blot analyses. The peroxidase-labeled bovine Lf (BLf) and human Lf both recognized a heat-modifiable protein with an estimated molecular mass of 38 kD in the OM. Simultaneous immunoblotting with an antiporin monoclonal antibody specific for a conserved porin domain in members of enterobacteriaceae confirmed that the Lf-binding protein is a porin. Such Lf-binding porin proteins (37-39 kD range) were readily detected in nine other common Salmonella species: S. dublin, S. panama, S. rostock, S. abony, S. hartford, S, kentucky, S. pullorum, S. thompson, and S. virchow. The latter six species also demonstrated one to three weak Lf-reactive bands of low molecular weight in their CE. The antibiotic susceptibility of Salmonella in the presence of Lf was examined. A mixture containing sub-minimum inhibitory concentration (MIC) levels of Lf (MIC/4) and cefuroxime (MIC/2) inhibited the bacterial growth. Lf strongly potentiated the action of erythromycin (eightfold), whereas it increased the activity only by two-fold for ampicillin, ciprofloxacin, chloramphenicol, and rifampicin; similarly, these antibiotics also reduced the MIC of BLf by twofold in S. typhimurium. Such antimicrobial potentiation was not observed with BLf mixtures containing cefalexin, gentamycin, or polymyxin B against strain ATCC13311. BLf and cefuroxime also demonstrated potentiation of varying degrees (two to 16-fold) with nine other Salmonella species. These data established the binding of Lf to porins in salmonellae and a potentiation effect of Lf with certain antibiotics. PMID- 7867308 TI - Rapid detection of hyaluronic acid capsules on group A streptococci by buoyant density centrifugation. AB - One of the virulence factors of group A streptococci is the hyaluronic acid polysaccharide capsule. A rapid method for ascertaining the status of the capsule phenotype in Streptococcus pyogenes is described. Bacteria with a capsule have a lower buoyant density than acapsular or hyaluronidase-treated cells. Early log phase cultures were underlaid with 65% Percoll and centrifuged at 500-1000 g for 5 min. Upon visual examination, encapsulated cells were observed at the interface, whereas acapsular cells appeared in the pellet. Cultures that produced at least 7 micrograms/ml of hyaluronic acid per A600 unit of cells were detected at the interface; this level of polysaccharide is only about 0.5%-4% of that found for most mucoid strains. Therefore, this procedure can detect capsules around strains that do not appear to be encapsulated by light microscopy or do not possess mucoid colony morphology. Furthermore, this method reduces dependence on other expensive assays that use labile radioactive reagents to detect hyaluronic acid. PMID- 7867309 TI - Evaluation of 80% inhibition standards for the determination of fluconazole minimum inhibitory concentrations in three laboratories. AB - The purpose of this study was to evaluate 1:5 growth control dilutions (80% inhibition standards) to determine fluconazole minimum inhibitory concentration (MIC) end points in three laboratories. We tested 39 selected Candida species (in vitro susceptible: fluconazole MIC of < or = 1 microgram/ml, and resistant: fluconazole MIC of > or = 8 micrograms/ml) and Cryptococcus neoformans isolates by broth macro- and microdilution procedures following the National Committee for Clinical Laboratory Standards proposed reference method for yeasts (M27-P). Macrodilution MIC80% were the lowest drug concentrations with turbidity (growth) less than or equal to that of specific 1:5 dilutions of the growth control. Microdilution MICs-2 were the lowest drug concentrations in which there was prominent decrease of growth. A total of 1608 MICs were evaluated. C. krusei, C. parapsilosis, and C. tropicalis strains had reproducible fluconazole MICs by both tests (24 and 48 h). Fluconazole MIC80% and MIC-2 end points were consistent at 24 h (with C. albicans) and more variable at 48 h. MICs of C. neoformans were more reproducible at 72 h than at 48 h by both tests. This study suggests that the determination of fluconazole MICs is dependent on the length of incubation and the yeast being tested, and that antifungal testing of the yeasts may be performed by either test. PMID- 7867310 TI - Comparison of fluconazole minimum inhibitory concentrations in three different formulations of RPMI-1640. AB - This study aimed to compare the susceptibilities of fluconazole, obtained in two laboratories, using three RPMI-1640 formulations (manufacturers') and inhibition standards (80%). A total of 39 selected Candida species (in vitro susceptible and resistant) and Cryptococcus neoformans isolates were tested in each medium by broth macro- and microdilution procedures following the National Committee for Clinical Laboratory Standards proposed reference method (M27-P). Macrodilution minimum inhibitory concentrations (MIC80%) were the lowest drug concentrations with turbidity (growth) less than or equal to that of the specific 80% inhibition standards (1:5 growth control). Microdilution MIC-2 were the lowest drug concentrations in which there was prominent decrease in growth. In general, the three formulations of RPMI-1640 medium provided similar MICs for most of the yeasts tested in both laboratories and by each test. PMID- 7867311 TI - Update of lomefloxacin in vitro activity and spectrum. A multicenter trial testing contemporary pathogens following Food and Drug Administration validation guidelines. Lomefloxacin Activity Study Group. AB - The United States Food and Drug Administration recently recommended that the antimicrobial product package insert (PPI) subsection on microbiology be annually validated with regard to the compound's spectrum and potency. To address this request, a nine-laboratory trial was organized to test (two methods) lomefloxacin, a newer fluoroquinolone, and nine comparison drugs against PPI listed pathogens (1934 strains). A broad geographic sampling (nine medical centers) was achieved, and lomefloxacin was determined to be active [minimum inhibitory concentration (MICs), < or = 2 micrograms/ml for > or = 90% of strains] for all PPI-listed species except Pseudomonas aeruginosa, Citrobacter freundii, and Providencia rettgeri (42%-87% inhibited). Comparison fluoroquinolones also had a similarly compromised spectrum of activity against these species. Additional organism species, including Neisseria gonorrhoeae, N. meningitidis, Salmonella enteriditis, and Shigella species, should be added to the lomefloxacin PPI (MIC90s, 0.03-0.25 microgram/ml) following data generated in this study. These in vitro results indicate that lomefloxacin remains active against the vast majority of clinically "indicated" species, and that it has a spectrum compatible with other marketed fluoroquinolones for these tested pathogens, monitored in 1994. PMID- 7867312 TI - Aspergillus peritonitis in a continuous ambulatory peritoneal dialysis patient. Case report and review of the literature. AB - Aspergillus peritonitis is a rare but treatable complication of continuous ambulatory peritoneal dialysis. We report a case of Aspergillus peritonitis in a continuous ambulatory peritoneal dialysis patient and review the nine other cases reported in the literature. The course was often insidious, and the clinical manifestation and laboratory findings were similar to those of bacterial peritonitis. The distinctive feature of these cases was the persistence of symptoms despite broad-spectrum antibiotics. Catheter removal is of crucial importance in the management of this disease. PMID- 7867313 TI - An empirical method to refine personality disorder classification using stepwise logistic regression modeling to develop diagnostic criteria and thresholds. AB - This study of DSM-III-R personality disorder (PD) classification provides an empirical approach to determine (1) the discriminative power of each criterion and (2) the optimal number of criteria needed to diagnose the presence of each PD. A semistructured assessment of 110 outpatients was performed for the 11 PDs and their 104 diagnostic criteria. Sensitivity, specificity, and predictive powers were calculated for each criterion item. Logistic regression was performed to determine (1) univariate weightings of the individual criteria as applied to a given diagnosis, and (2) multivariate measures of the criteria that significantly improved the chi-square value in a stepwise fashion. The significant items were then equally weighted to calculate the optimal number needed to diagnose category membership. Of 104 PD criteria, 41 discriminated at a significance level of .05 or less, and each PD could be optimally diagnosed with fewer criteria than currently required. We can empirically reduce the number of criteria combinations comprising individual categories, decrease heterogeneity, and narrow diagnostic boundaries. This increases the likelihood of identifying etiological factors, predictors of clinical course, specific treatments, familial aggregation, and neurobiological correlates for the PD taxa. PMID- 7867314 TI - Are schizophrenia and affective disorder related?: the problem of schizoaffective disorder and the discrimination of the psychoses by signs and symptoms. AB - Schizophrenia and affective disorder are separately classified. Schizoaffective disorder has been considered a variant of these, or representing several diseases. Some hypothesize a psychosis continuum. One test of these contrasting views involves discriminating the psychoses by their classic symptoms. We used discriminant function analyses to assess the ability of systematically recorded psychopathology to distinguish 167 DSM-III schizophrenics from 74 affectives. We divided the schizophrenics into chronic and schizoaffective subgroups. We discriminated chronic schizophrenics from affectives, but schizoaffectives overlapped both groups. Schizoaffective/unipolars were like chronic schizophrenics, and schizoaffective/bipolars were like affectives. However, these discriminations also substantially overlapped, and among non-affective positive features formal thought disorder was best at discrimination. Our findings do not fully support the present classification system, and suggest that its emphasis on hallucinations and delusions is overvalued. PMID- 7867315 TI - An analysis of the subjective experience of schizophrenia. AB - To examine how varieties of the subjective experience of schizophrenia (SES) can be categorized, a self-report questionnaire consisting of 150 items from the SES in Japanese was administered to 237 Japanese schizophrenic inpatients, and the results were analyzed through a multivariate method. The first factor represents loss of focus and adequacy of thoughts, behavior, and interpersonal perception; it resembles negative symptoms and coincides with the basic symptoms of schizophrenia reported by anthropological psychiatrists. The second factor represents automatic and excessive thoughts and affective loading, and overlaps "the tremble" of Conrad and the mental automatism of de Clerambault. Both signify different combinations of experiences from conventional descriptive symptoms, and may represent more suitable ways to describe the SES. PMID- 7867316 TI - Premorbid functioning in schizophrenia: a controlled study of Nigerian patients. AB - We compared the premorbid social adjustment of 38 schizophrenic patients with that of 20 manic patients. Even though the small sample size affected the number of significant differences obtained, schizophrenic patients consistently showed evidence of poorer premorbid functioning than manics at various stages of social development. Schizophrenic men also tended to have functioned more poorly than women. Poor premorbid functioning was associated with negative syndrome, but not with positive or disorganization syndromes. Our findings suggest that poor premorbid adjustment is an early sign of schizophrenic illness even among patient populations who may be characterized by good short-term outcome. PMID- 7867317 TI - Comparative study of diagnostic systems: Chinese Classification of Mental Disorders-Second Edition versus DSM-III-R. AB - We report on the diagnostic comparative study of the Chinese Classification of Mental Disorders-Second Edition (CCMD-2) and the DSM-III-R in a field trial in China. The Adult Diagnostic Interview Schedule-Second Edition (ADIS-2), a modified diagnostic interview schedule that can generate both CCMD-2 and DSM-III R diagnoses, was used to test 254 psychiatric patients in China. It was found that the reliability and validity of the CCMD-2 and DSM-III-R are compatible in most diagnostic categories such as schizophrenia, delusional disorder, bipolar disorders, and depressive disorders. The discrepancies between Chinese and American diagnostic systems were found mainly in neurasthenia and hysterical neuroses. Such discrepancies may have resulted from frequent changes of the diagnostic terms in the West, such as the phenomenon of neurasthenia, or from creating a new disorder entity in CCMD-2, such as "Eastern gymnastic exercises induced mental disorder. "Further cross-cultural studies focusing on these discrepant disorders are urgently needed to understand the cultural influences on diagnosis, as well as to improve the professional classification of mental disorders in different diagnostic systems. PMID- 7867319 TI - Long-term follow-up of depression in seasonal affective disorder. AB - Twenty-six patients diagnosed as having seasonal affective disorder (SAD) completed weekly depression self-ratings for at least 2.5 and up to 8.25 years. Seasonal recurrence of depression persisted in nine patients, seven remitted, four were chronically depressed, and six showed a diffuse pattern. The age at SAD onset and duration of SAD history before entry into this prospective study could not be identified as predictors of the subsequent course of the disease. Short lasting, recurrent periods of depression could be identified in many of the long term records. They were found primarily in autumn and winter in patients with either a persistent seasonal or a remitted pattern. In the core group of patients with persistent seasonal pattern, the onset and offset of depressive periods (DPs) were more variable than the DSM-III-R 60-day window criterion for seasonal pattern allows. PMID- 7867318 TI - Seasonal patterns in eating disorder subgroups. AB - Patients with bulimia nervosa (BN) often have seasonal patterns of mood and appetite that compare with patterns seen in seasonal affective disorder (SAD). Seasonal patterns in other eating disorder (ED) subgroups have not been adequately described. We report on seasonal patterns in mood, weight, appetite, sleep, social activity, and energy in 154 consecutive admissions to an outpatient ED program: 60 patients with anorexia nervosa (AN), 31 with BN, 34 with a history of both AN and BN (AN/BN), and 29 with an ED not otherwise specified (ED-NOS). AN patients had significantly less seasonal variation overall than either bulimic subgroup, as measured by the global seasonality score (GSS) on the Seasonal Patterns Assessment Questionnaire (SPAQ). AN patients also showed less seasonal change in mood, weight, and energy than BN patients, and less variation in mood and appetite than AN/BN patients. PMID- 7867320 TI - The relationship between characteristics of sexual abuse and dissociative experiences. AB - Childhood sexual abuse has been associated with adult dissociative symptomatology. The purpose of this study was to examine the relationship between specific characteristics of sexual abuse and dissociative experiences in adulthood. Fifty-six female inpatients with a history of physical abuse and severe sexual abuse reported on their history of abuse and dissociative experiences. A logistic regression that controlled for physical revictimization showed that sexual abuse by a greater number of different sex abuse offenders was significantly related to an elevated level of dissociation. In exploring how many sex abuse offenders are associated with dissociative experiences, a logistic regression revealed a significant relationship between four or more sex abuse offenders and greater dissociative symptomatology. The reported age of onset of the sexual abuse was not a significant predictor of dissociation when sexual revictimization was included in the analysis. These findings suggest that severely traumatized patients with a history of multiple sex abuse offenders are highly likely to use dissociation as a primary psychological defense. The implications of the study are discussed. PMID- 7867321 TI - Pseudoseizures, sexual abuse, and hermeneutic reasoning. AB - It has been proposed that pseudoseizures are a symbolic expression of having been sexually abused. Such reasoning is hermeneutic in nature and potentially damaging if uncritically used. Sexual abuse is one of several risk factors for pseudoseizures, but it should not be deduced simply from the occurrence or form of the conversion disorder. PMID- 7867322 TI - Battle against therapeutic nihilism in caring for patients who exhibit the negative symptoms of schizophrenia (NSS) PMID- 7867323 TI - The modulation of skin irritation. AB - Irritant contact dermatitis (ICD) is a multifactorial disease, the onset and modulation of which depend on both endogenous and exogenous factors. Among the former, age, race, site, sex and history of dermatitis may all be important. Such variables can now readily be quantified by objective noninvasive techniques, such as measurement of transepidermal water loss (TEWL). Moreover, effects of irritants on the epidermis are related to the particular chemical properties of each molecule, contributing further to clinical heterogeneity. Release of cytokines and mediators may be initiated by a number of cells, including living keratinocytes and those of the stratum corneum, thus modulating inflammation and repair. Furthermore, differences in mechanisms of inflammation between acute and chronic ICD may exist, the former being characterized predominantly by inflammation, the latter by hyperproliferation and transient hyperkeratosis. These findings may explain the complexity and difficulty of investigating ICD. Better understanding and quantification of these mechanisms may lead to identification of high-risk individuals and more effective prevention and treatment. PMID- 7867324 TI - Allergic contact dermatitis from the synthetic fragrances Lyral and acetyl cedrene in separate underarm deodorant preparations. AB - The case is reported of a 28-year-old man who developed allergic contact dermatitis from 2 synthetic fragrance ingredients, Lyral (3- and 4-(4-hydroxy-4 methylpentyl)-3-cyclohexene-1-aldehyde) and acetyl cedrene, in separate underarm deodorant preparations. The implications of the patient's negative patch test reactions to the European standard series (Trolab) and cosmetics and fragrance series (both Chemotechnique Diagnostics) are discussed. The importance is stressed of patch testing with the patient's own preparations when cosmetic dermatitis is suspected, and of identifying and reporting offending fragrance ingredients, with a view possibly to updating the European standard series and commercially available cosmetics and fragrance series. PMID- 7867325 TI - The influence of shaving method on perfume allergy. AB - Among men, the most frequent contact allergens are perfumes (fragrance mix and balsam of Peru). Considering that the main cause of nickel allergy is ear piercing, shaving with a razor blade might be the cause of perfume contact allergy, by creating small wounds that increase the penetration of applied perfume substances derived from soaps, shaving foams and after-shave lotions. 19 males with contact allergy to fragrance mix and/or to balsam of Peru were interviewed about their shaving habits by letter. 17 responded (89%), of whom 12 (71%) had been using razor blades continuously for a period of at least 1 year. At our clinic, the frequency of razor blade usage was found to be 45% in patch tested men without perfume contact allergy. When comparing the frequencies of razor blade usage among patch tested men with and without perfume contact allergy, there was a statistically significant over-representation (p = 0.047) among those with perfume allergy. The risk of perfume allergy when using razor blades was found to be 2.9 (odds ratio). PMID- 7867326 TI - Sensitization to thimerosal (Merthiolate) is still present today. AB - The results on thimerosal (Merthiolate) hypersensitivity of a retrospective study, together with the relevant data on thimerosal hypersensitivity referred to in the literature up to 1993, are presented. Positive patch test reactions to thimerosal (0.1% pet.) were observed in 32 (1.3%) of 2461 adult patients with suspected contact allergy examined in the period 1987-1992. 20 (0.8%) patients had a solitary positive patch test to thimerosal. The observed incidence is low. Clinical symptoms related to thimerosal hypersensitivity were observed in only 3 patients. The collected results are discussed with emphasis on the clinical implications of sensitization to thimerosal. It appears that a positive patch test to thimerosal is frequently clinically irrelevant. PMID- 7867327 TI - Nickel release from metals, and a case of allergic contact dermatitis from stainless steel. AB - The prevalence of allergic contact dermatitis (ACD) caused by nickel is increasing. The probable cause is the increased use of nickel-containing metals in intimate contact with the skin. The critical factor is the amount of nickel released from these metals (bioavailable nickel) onto the skin. In the present study, we determined, with flame atomic absorbtion spectrometry, the amount of nickel released into synthetic sweat from metal samples. The results of this method were compared with the results of the dimethylglyoxime (DMG) test, which is considered to be a reliable means of identifying whether nickel-containing metals may cause allergy symptoms in sensitive individuals. Out of 10 samples studied, only small amounts (< 0.5 microgram/cm2/week) were released from 2 samples, and the DMG test was negative. From 5 samples, more than 0.5 microgram/cm2/week was released, and the DMG test was positive. For 3 samples, however, the DMG test was negative, though the flame atomic absorption spectrometry test showed considerable release of nickel. Therefore, although the DMG test can be used as a first line test for determining nickel release, some DMG-negative metal materials probably induce nickel sensitization, and should by no means be advertised as safe in this respect. We also report a nickel-allergic patient who developed ACD from stainless steel, indicating that some types of stainless steel release enough nickel to elicit allergic symptoms. PMID- 7867328 TI - Metal allergy in north Norwegian schoolchildren and its relationship with ear piercing and atopy. AB - In 424 schoolchildren (223 boys and 201 girls) aged 7-12 years undergoing routine patch tests, 21.0% (89 children), 38.8% (78/201) of girls and 4.9% (11/223) of boys, had had their ears pierced. 18.6% (79 children, 55 girls and 24 boys) gave a history of cutaneous reactions to metallic jewelry, and in 17.2% (73 children, 49 girls and 24 boys), sensitivity to one or more metals was confirmed. Metal allergy was confirmed by patch testing in only 34.2% of the children with a history of metal dermatitis, and 13.3% of those without a history of metal reactions had, in fact, positive patch tests to 1 or more metals. The low sensitivity (37.0%) and low positive predictive value (34.2%), together with high specificity (85.2%) and high negative predictive value (86.7%), seem to justify dermatological examination of individuals with a positive symptom-based diagnosis only. Nickel sensitivity was found in 14.9% (63 children, 44 girls and 19 boys). There is clearly a relationship between ear piercing and induction of nickel allergy in girls, as nickel sensitivity in girls with pierced ears was 2x (30.8%) that found in those without (16.3%) pierced ears. In boys, nickel sensitivity was much less frequent and few cases were related to ear piercing. Atopy appeared to influence the propensity for developing metal sensitivity in girls, as atopic girls showed positive metal tests 2x as frequently (30.8%) as non-atopic (17.0%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867329 TI - Food-induced contact urticaria syndrome (CUS) in atopic dermatitis: reproducibility of repeated and duplicate testing with a skin provocation test, the skin application food test (SAFT). AB - IgE-mediated contact urticaria syndrome (CUS) is one of the manifestations of allergy in childhood atopic dermatitis (AD). Allergens such as foods and animal products penetrate the skin easily. They can then cause urticarial reactions in sensitized individuals. A provocation test system for foods, called the skin application food test (SAFT), has been developed. Over more than 5 years, a group of 175 patients with AD was built-up and investigated in a prospective follow-up study with SAFT. SAFT was more frequently positive in AD children aged 0-2 years than in older children. In several children of this population (Group 1), we repeated SAFT within a period of 1 year. In another unrelated group of children (Group 2-1), we compared the results of 'original' SAFT and SAFT using square chambers (Van der Bend) or Silver patches. In the 3rd group (Group 2-2) we compared 'original' SAFT with SAFT using big Finn Chambers. The agreement between the tests was high: in Group 1, we observed 88 to 93% concordant scores, and in Group 2, the scores were 96% to 100%. Statistically, the kappa coefficient ranged from 0.71-0.87 in Group 1, and from 0.83-1.00 in Group 2. SAFT is therefore highly reproducible. Agreement was at least > or = 88% between the scores (the lowest kappa value observed was at least 0.71). PMID- 7867330 TI - Patch testing for allergy to beta-lactam antibiotics. PMID- 7867331 TI - Occupational contact dermatitis from amine-functional methoxysilane in continuous glass-filament production. PMID- 7867332 TI - Prevention of allergic contact dermatitis with alternative products. PMID- 7867333 TI - Allergic contact dermatitis from tocopheryl acetate (vitamin E) and retinol palmitate (vitamin A) in a moisturizing cream. PMID- 7867334 TI - Patch tests after cyclosporin A treatment in hyperreactive patients. PMID- 7867335 TI - Prevention of allergic contact dermatitis from nail varnishes and hardeners. PMID- 7867336 TI - Allergic contact dermatitis in HIV-positive patients. PMID- 7867337 TI - Tylosin, an airborne contact allergen in veterinarians. PMID- 7867338 TI - Occupational contact sensitization to ethylenediamine in a nurse. PMID- 7867339 TI - Allergic contact dermatitis due to mercury in a wedding ring and a cosmetic. PMID- 7867340 TI - Allergic contact dermatitis from cyanamide: report of 3 cases. PMID- 7867341 TI - Colophony in paper-based surgical clothing. PMID- 7867342 TI - Determination of monomers in epoxy resin hardened at elevated temperature. PMID- 7867343 TI - A look at pediatric intensive care--Dutch style. PMID- 7867344 TI - Barotrauma in acute lung injury: is it important? PMID- 7867345 TI - Inverse ratio ventilation--simply an alternative, or something more? PMID- 7867346 TI - Predicting mortality in septic patients. PMID- 7867347 TI - Beneficial effects of combined thromboxane and leukotriene receptor antagonism in hemorrhagic shock. AB - OBJECTIVE: Both thromboxane A2 and peptide leukotrienes D4/E4 have been implicated in the pathophysiology of circulatory shock. In the present study, we evaluated the effect of thromboxane A2 and leukotriene D4/E4 receptor antagonism in circulatory shock. DESIGN: Prospective, randomized, controlled trial. SETTING: Research laboratory. SUBJECTS: Male Sprague-Dawley rats (325 to 375 g). INTERVENTIONS: The effect of selective receptor antagonists of thromboxane A2 (i.e., SQ-29,548) and leukotrienes D4/E4 (i.e., LY-171883) was investigated, either alone or in combination, in a model of hemorrhagic circulatory shock. Animals were randomly assigned to one of eight experimental groups: a) sham plus vehicle; b) sham plus LY-171883 (4 mg/kg); c) sham plus SQ-29,548 (2 mg/kg); d) sham plus SQ-29,548 (2 mg/kg) plus LY-171883 (4 mg/kg); e) hemorrhage plus vehicle; f) hemorrhage plus LY-171883 (4 mg/kg); g) hemorrhage plus SQ-29,548 (2 mg/kg); and h) hemorrhage plus SQ-29,548 (2 mg/kg) plus LY-171883 (4 mg/kg). Circulatory shock was induced by acute hemorrhage to a mean arterial pressure (MAP) of 45 mm Hg. We investigated the effect of SQ-29,548 and LY-171883 on the progression of circulatory shock. MEASUREMENTS AND MAIN RESULTS: Neither pharmacologic agent, alone or in combination, had any significant effect on MAP or heart rate in nonhemorrhaged rats. Both thromboxane receptor antagonism (p < .01) and combined thromboxane/leukotriene receptor antagonism (p < .001) significantly improved survival time after hemorrhage. However, leukotriene receptor antagonism alone did not significantly improve survival time after hemorrhage. After acute blood loss and 20% decompensation, the shed blood was returned to the animal; maximal postreinfusion blood pressures were not significantly different between experimental groups. The postreinfusion MAP was maintained at higher values in hemorrhaged rats given the thromboxane receptor antagonist or the combination of thromboxane and leukotriene receptor antagonists. Only the combined therapy significantly altered all of the measured indices of cardiovascular compensation (i.e., maximum bleed-out volume, time to maximum blood loss, and 20% decompensation time). Furthermore, only combined receptor antagonism resulted in a significant (p < .02) attenuation of plasma cathepsin D activity. CONCLUSIONS: The present findings support a role for thromboxane A2 and peptide leukotrienes D4/E4 as important mediators in circulatory shock and suggest that combined thromboxane/leukotriene receptor antagonism may have superior therapeutic efficacy to leukotriene receptor antagonism. PMID- 7867348 TI - Comparative assessment of pediatric intensive care: a national multicenter study. Pediatric Intensive Care Assessment of Outcome (PICASSO) Study Group. AB - OBJECTIVE: Comparative assessment of performance of pediatric intensive care. DESIGN: Open, prospective multicenter study. SETTING: All pediatric intensive care units (n = 10; six tertiary and four nontertiary) in the Netherlands. PATIENTS: 1063 consecutive unselected admissions, < or = 18 yrs old, during a 4 month period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Effectiveness was defined as the ratio of observed to expected (Pediatric Risk of Mortality score-derived) mortality. Efficiency was determined by two objective criteria: mortality risk of > 1%, or administration of at least one intensive care unit (ICU)-dependent therapy. In the total population, observed and expected mortality rates were similar. Between hospitals, crude mortality showed wide variations (mean 7.1%, range 1% to 10%). However, in each center, observed and expected mortality rates were similar (mean ratio of observed/expected mortality 0.99, range 0.8 to 1.5). In tertiary care centers, severity of illness-corrected mortality rates in high-risk patients were less than in a United States reference population. Paradoxically, in low-risk tertiary care patients, the observed mortality rate was higher than expected. The relatively high mortality rate in this group is probably the result of the large number of low-risk tertiary care patients suffering from severe, incurable chronic disease. The average number of efficient ICU days was 72%, although large fluctuations between units were found (range 22% to 95%), suggesting that in several centers efficiency rates might be improved by a better selection of high-risk patients requiring ICU-dependent therapies. CONCLUSIONS: Differences in mortality rates among pediatric ICUs were largely explained by differences in severity of illness. High efficiency rates combined with adequate effectiveness were found in several centers, indicating that admission and discharge decisions might be improved in less efficient centers. PMID- 7867349 TI - Relationship between blood lactate concentrations and ionized calcium, glucose, and acid-base status in critically ill and noncritically ill patients. AB - OBJECTIVE: To determine the relationships between circulating blood lactate concentrations and several biochemical variables including ionized calcium, glucose, pH, and acid-base status in critically ill and noncritically ill patients. DESIGN: A prospective, cohort study. SETTING: The critical care research laboratory, intensive care unit (ICU), emergency room (ER), and general ward of a 466 bed university-affiliated hospital. PATIENTS: Three-hundred thirty four critically ill and noncritically ill patients. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Circulating blood lactate concentrations, ionized calcium concentrations, blood glucose, pH, and base deficit values were simultaneously determined in blood samples from various patient populations. Descriptive data and physiologic parameters were also recorded. Circulating lactate and ionized calcium determinations were performed simultaneously in 334 whole blood samples from 334 subjects. There was neither a statistically significant nor clinically relevant correlation between circulating lactate concentrations and ionized calcium concentrations when lactate values were < or = 2 mmol/L (p = 0.8962, r2 = .01) or when lactate values were > 2 mmol/L (p = .3697, r2 = .09) in a heterogeneous patient population. Our study populations included five subject groups: a) nonhypotensive ICU patients (n = 93), b) nonhypotensive ER patients (n = 85), c) nonhypotensive general ward patients (n = 44), d) hypotensive patients from the ICU, ER, and general wards (n = 39), and e) normal controls (n = 73). There was neither a statistically significant nor clinically relevant correlation between circulating lactate concentrations and ionized calcium concentrations in each of the five populations studied for lactate values either < or = 2 mmol/L or > 2 mmol/L. We studied the relationship between circulating lactate concentrations and blood glucose concentrations (n = 334 patients), arterial pH and base deficit (n = 163 patients), and venous pH and base deficit (n = 171 patients). Statistically significant, but perhaps not clinically relevant correlations were observed when comparing circulating lactate values with blood glucose values (p = .0330, r2 = .12), arterial pH (p = .0007, r2 = .26) and base deficit from arterial specimens (p = .0014, r2 = .25). There were neither statistically significant nor clinically relevant correlations when comparing circulating lactate concentrations with venous pH (p = .9098, r2 = .01) or base deficit determined from venous blood specimens (p = .1365, r2 = .11). CONCLUSIONS: a) There is neither a statistically significant nor clinically relevant relationship between whole blood lactate concentrations and ionized calcium concentrations when studying patients with or without hyperlactatemia. b) Although there is a statistically significant correlation between circulating lactate concentrations and blood glucose concentrations, arterial pH or arterial base deficit, such associations do not appear to be clinically important. PMID- 7867350 TI - L-arginine: nitric oxide pathway in endotoxemia and human septic shock. AB - OBJECTIVE: To investigate the relationship between nitric oxide production, endotoxemia, and hemodynamic alterations in human septic shock. DESIGN: Prospective study. SETTING: A 32-bed intensive care unit in a university referral hospital. PATIENTS: Two groups of septic patients with shock (n = 13) or without shock (n = 16) and an additional group of nonseptic patients as control group (n = 25). MEASUREMENTS: Plasma nitrite and nitrate concentrations were measured as an index of nitric oxide generation. Nitrite and nitrate concentrations were correlated with plasma endotoxin and hemodynamic variables. MAIN RESULTS: Increased plasma nitrite and nitrate concentrations were found in patients with septic shock (p < .01). Nitrite and nitrate correlated directly with endotoxin concentration (r2 = .21, p < .05) and cardiac output (r2 = .49, p < .05), and inversely with systolic blood pressure (r2 = .24, p < .01). CONCLUSIONS: This study demonstrated the activation of the L-arginine:nitric oxide pathway in human endotoxemic septic shock, suggesting that nitric oxide may be an important mediator of the hemodynamic disturbances in this pathophysiologic situation. PMID- 7867351 TI - Microvascular function and rheologic changes in hyperdynamic sepsis. AB - OBJECTIVE: To investigate the rheologic changes and circulatory abnormalities at the microvascular level during severe sepsis. DESIGN: Prospective, controlled trial. SETTING: Medical and surgical intensive care units of a university affiliated hospital. PATIENTS: Nine normal controls and eight adult patients with severe sepsis who met the study entrance criteria. INTERVENTIONS: Forearm blood flow was measured at rest and during reactive hyperemia by air plethysmography. Simultaneous hemodynamic measurements and blood samples for rheologic measurements were taken. MEASUREMENTS AND MAIN RESULTS: Red blood cell deformability index was determined using a simple filtration procedure. Leukocyte aggregation in whole human blood was detected by using a leukergy test. Expression of the neutrophil adhesion molecule CD11b/CD18 was measured using a monoclonal antibody and flow cytometry. All data were taken within 24 hrs of the patient meeting criteria for entrance into the study. Cardiac output, oxygen delivery, and oxygen consumption measurements were consistent with the hyperdynamic phase of severe sepsis. Forearm blood flow was significantly (p < .05) greater in septic patients (21 +/- 3 mL/min) than in controls (12 +/- 2 to 36 +/- 5 mL/min (p < .05), while in the septic patients, forearm blood flow during reactive hyperemia increased from 21 +/- 3 to 32 +/- 4 mL/min. The ratio of forearm blood flow during reactive hyperemia to forearm blood flow at rest was 3.2 +/- 0.1 in the controls and 1.6 +/- 0.1 in the septic patients (p < .01). The red blood cell deformability index in whole blood was significantly (p < .01) decreased in the septic patients compared with the control subjects (0.41 +/- 0.07 vs. 0.98 +/- 0.08 mL/min). This difference remained true when the hematocrit was adjusted to 45% (0.82 +/- 0.06 vs. 1.04 +/- 0.06 mL/min; p < .05). Increased expression of the neutrophil adhesion molecule CD11b/CD18 was observed in septic patients (349 +/- 46 logarithmic fluorescence units) as compared with control subjects (233 +/- 26 logarithmic fluorescence units; p < .05). Leukergy was also significantly (p < .05) increased in septic patients (17.7 +/- 3.8%) as compared with control subjects (8.9 +/- 1.6%). A significant correlation was observed between leukergy and the expression of the neutrophil adhesion molecule CD11b/CD18 in controls and septic patients (r2 = .62; p < .01). Leukergy was also inversely correlated with whole blood red blood cell deformability index (r2 = .28; p < .05). CONCLUSIONS: Reactive hyperemia in the forearm is significantly diminished in patients with sepsis, suggesting impaired microvascular blood flow. Rheologic changes, including impaired red blood cell deformability, increased leukocyte aggregation, and endothelial adherence, may contribute to this abnormality by compromising effective capillary cross-sectional area. PMID- 7867352 TI - Frequency and importance of barotrauma in 100 patients with acute lung injury. AB - OBJECTIVES: To determine the occurrence rate of barotrauma in acute lung injury patients, whether barotrauma is an independent risk factor for mortality, and the role of barotrauma in the outcome of those patients who died. DESIGN: Prospective, cohort study. SETTING: Intensive care units at a university hospital. PATIENTS: Consecutive adult patients (n = 100) meeting the usual criteria for a diagnosis of acute lung injury requiring mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Barotrauma occurred in 13 (13%) of 100 patients. Mortality rates were not different in patients with (76%) and without (64%) barotrauma. Using univariate analysis, barotrauma was not associated with increased mortality (odds ratio 1.85; confidence interval 0.42 to 9.20; p = .53). However, when barotrauma was incorporated into a logistic regression model, along with other potential predictors of mortality, barotrauma was associated with increased mortality (odds ratio 6.15; confidence interval 1.11 to 33.9; p = .017). The presence of nonpulmonary organ dysfunction and sepsis was strongly associated with mortality. In the setting of barotrauma, the mortality rate was 100% if associated with two or more nonpulmonary organ dysfunctions compared with a mortality rate of 40% with one or no nonpulmonary organ failure. Barotrauma contributed directly to the cause of death in only one patient. CONCLUSIONS: Barotrauma occurred in only 13% of patients with acute lung injury. Barotrauma was an independent marker of mortality when adjusted for other predictors of mortality. However, barotrauma directly contributed to < 2% of all deaths. We hypothesize that barotrauma is an indication of severity of acute lung injury rather than a major cause of increased mortality. PMID- 7867353 TI - Pressure-controlled, inverse ratio ventilation that avoids air trapping in the adult respiratory distress syndrome. AB - OBJECTIVES: To investigate physiologic and outcome data in patients switched from volume-cycled conventional ratio ventilation to pressure-controlled inverse ratio ventilation that did not produce air trapping and intrinsic positive end expiratory pressure (PEEP). SETTING: Medical intensive care unit. DESIGN: Retrospective analysis of crossover data and outcome. PATIENTS: Fourteen patients with the adult respiratory distress syndrome who were receiving mechanical ventilation with volume-cycled, conventional ratio ventilation followed by pressure-controlled, inverse ratio ventilation. INTERVENTIONS: Our approach to pressure-controlled, inverse ratio ventilation was to use tidal volumes and applied PEEP values comparable to those volumes and values used on volume-cycled, conventional ratio ventilation, use inspiratory times to increase mean airway pressure instead of additional applied PEEP, and avoid air trapping (intrinsic PEEP). MEASUREMENTS AND MAIN RESULTS: With this approach, there was a reduction in peak airway pressure from 53 +/- 8.5 (SD) to 40 +/- 5.9 cm H2O (p < .01), and an increase in mean airway pressure from 20 +/- 3.9 to 30 +/- 5.2 cm H2O (p < .01). Tidal volume, mean inflation pressure, and compliance did not change. Oxygenation (PaO2) improved from 57 +/- 11.3 torr (7.6 +/- 1.5 kPa) to 94 +/- 40.2 torr (12.5 +/- 5.4 kPa) (p = .01) but the oxygenation index (mean airway pressure x FIO2 x 100/PaO2) did not change significantly (25.9 +/- 10.3 to 27.2 +/- 12.2). There was no significant change in PaCO2 or pH even though delivered minute ventilation decreased from 17.4 +/- 4.3 to 14.8 +/- 5.8 L/min (p = .02). Cardiac index slightly decreased, but hemodynamic values were otherwise stable. Only three of the 14 study patients survived. CONCLUSIONS: These data demonstrate that oxygenation is primarily a function of mean airway pressure, and that longer inspiratory times can be used as an alternative to applied PEEP to increase this oxygenation. If no air trapping develops, lung inflation pressures and delivered volumes remain constant with this approach. Because the technique was used only in patients refractory to conventional techniques, the poor outcome is not surprising. PMID- 7867354 TI - Comparison of propofol and midazolam for sedation in intensive care unit patients. AB - OBJECTIVES: To evaluate the comparative safety and effectiveness of intravenous infusion of propofol or midazolam when used for 12 to 24 hrs of sedation and to evaluate the quality of sedation during stimulation. DESIGN: An open, comparative, prospective, randomized study. SETTING: Surgical intensive care unit (ICU) in a university hospital. PATIENTS: Postoperative, intubated, general surgical, and orthopedic patients requiring mechanical ventilation (n = 60). INTERVENTIONS: None. MEASUREMENTS: Assessments were made at baseline (0 time), 5, 10, 15, 30, 45, and 60 mins; at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hrs; and at the end of sedation. The assessments included systolic, mean, and diastolic blood pressures, heart rate, two-lead electrocardiogram, pulse oximetry oxygen saturation, FIO2, end-tidal CO2, respiratory rate, ventilator rate, tidal volume, and sedation scale. Vital signs and the sedation scale were obtained at 30, 60, and 90 mins and at 2, 4, 12, and 24 hrs after the end of sedation. At approximately 8 hrs and 24 hrs (or at the end of sedation), the patient's CO2 production was calculated over a 5-min interval. Every 4 hrs, the nurse would summarize and rate patient response during stimulation as well as the overall rating of the sedation and patient ability to tolerate the ICU setting. MAIN RESULTS: There were no significant differences in pulse oximetry, arterial blood gas values, or respiratory measurements during sedation with propofol or midazolam. The mean heart rate was slower in the propofol group throughout the sedation and postsedation periods. The rating of sedation and tolerance of the ICU environment were significantly better for the propofol-treated group. Postsedation, the propofol group woke up faster on discontinuation of the sedative. CONCLUSIONS: Propofol was as safe and as efficacious as midazolam for continuous intravenous sedation. The quality of sedation was better in the propofol group. PMID- 7867355 TI - A look into the nature and causes of human errors in the intensive care unit. AB - OBJECTIVES: The purpose of this study was to investigate the nature and causes of human errors in the intensive care unit (ICU), adopting approaches proposed by human factors engineering. The basic assumption was that errors occur and follow a pattern that can be uncovered. DESIGN: Concurrent incident study. SETTING: Medical-surgical ICU of a university hospital. MEASUREMENTS AND MAIN RESULTS: Two types of data were collected: errors reported by physicians and nurses immediately after an error discovery; and activity profiles based on 24-hr records taken by observers with human engineering experience on a sample of patients. During the 4 months of data collection, a total of 554 human errors were reported by the medical staff. Errors were rated for severity and classified according to the body system and type of medical activity involved. There was an average of 178 activities per patient per day and an estimated number of 1.7 errors per patient per day. For the ICU as a whole, a severe or potentially detrimental error occurred on the average twice a day. Physicians and nurses were about equal contributors to the number of errors, although nurses had many more activities per day. CONCLUSIONS: A significant number of dangerous human errors occur in the ICU. Many of these errors could be attributed to problems of communication between the physicians and nurses. Applying human factor engineering concepts to the study of the weak points of a specific ICU may help to reduce the number of errors. Errors should not be considered as an incurable disease, but rather as preventable phenomena. PMID- 7867356 TI - Inhibitory effect of bile on bacterial invasion of enterocytes: possible mechanism for increased translocation associated with obstructive jaundice. AB - OBJECTIVE: To clarify the effect of bile salts on internalization of enteric bacteria by intestinal epithelial cells. DESIGN: Randomized study. SETTING: Research laboratory. SUBJECTS: Cultured human intestinal epithelial cells, namely HT-29 cells. INTERVENTIONS: The effect of bile was studied by adding bile during the time period in which bacterial cells were permitted to interact with enterocytes. In subsequent experiments, bile was added to the culture medium used to grow bacteria, and bacterial cells were washed before adding bacteria to enterocytes. Three different concentrations of three different bile preparations were tested. MEASUREMENTS AND MAIN RESULTS: Salmonella typhimurium and Proteus mirabilis were each incubated with HT-29 cells for 1 hr; the numbers of internalized bacteria were subsequently quantified following enterocyte lysis. The presence of bile during bacteria-enterocyte incubation had no effect on the numbers of internalized bacteria. However, if S. typhimurium or P. mirabilis were grown in the presence of bile, these washed bacterial cells were generally internalized by HT-29 cells in significantly fewer numbers, compared with bacterial cells grown in medium without bile supplementation. Enterocyte viability and morphologic ultrastructure did not appear to be affected by the presence of bile itself, or by the interaction with bacterial cells that had been cultivated in unsupplemented medium or in bile-supplemented medium. CONCLUSIONS: Exposure to bile during bacterial growth resulted in bacterial cells with decreased invasiveness for cultured intestinal epithelial cells. This observation is consistent with previous in vivo studies of obstructive jaundice, where the absence of bile in the intestinal lumen, not bile duct ligation, appeared to facilitate bacterial translocation in obstructed animals. Thus, the presence of bile in the intestinal lumen may decrease bacterial translocation by a mechanism that involves decreased epithelial internalization of enteric bacteria. PMID- 7867357 TI - Inhibitory effect of Escherichia coli endotoxin on skeletal muscle contractility. AB - OBJECTIVE: Endotoxemia in rabbits is associated with decreases in oxygen transport, tissue hypoxia, metabolic acidosis, and impaired oxygen extraction. In this study, we tested the hypothesis that endotoxin also inhibits skeletal muscle contractility directly. DESIGN: Randomized animal study. SETTING: Accredited animal research facility. SUBJECTS: New Zealand white rabbits of either sex, weighing 2.55 +/- 0.20 kg. INTERVENTIONS: We compared two groups of rabbits (n = 10 each) undergoing continuous electrical stimulation of the left hindlimb (maximal isometric twitch contraction at 0.25 Hz). One group (septic) was given an intravenous infusion of Escherichia coli endotoxin. The control group was subjected to decreases in cardiac output by inflating a balloon placed in the right ventricle. MEASUREMENTS AND MAIN RESULTS: Endotoxin or balloon inflation resulted in comparable decreases in cardiac output (49% and 53%, respectively). Hindlimb oxygen transport decreased to similar values for both groups (4.9 +/- 0.3 and 4.2 +/- 0.5 mL/min/kg, respectively). Systemic oxygen extraction ratio was greater in the control group (0.72 +/- 0.03) than in the septic group (0.55 +/- 0.04; p < .05). There were no differences in hindlimb oxygen extraction ratio. Decreases in hindlimb forces were greater in the septic group (42 +/- 4%) than in the control group (18 +/- 3%, p < .01). Force frequency curves obtained at the beginning and the end of the experiment showed greater fatigue in the septic group. CONCLUSIONS: The intravenous infusion of Escherichia coli endotoxin produces a direct inhibitory effect on skeletal muscle contractility in rabbits. This phenomenon is independent of decreases in oxygen transport and blood pH. Our data support the notion of a direct cellular effect of endotoxin, or of an associated cytokine, on skeletal muscle contractility. The mechanism responsible for this phenomenon is unknown. PMID- 7867358 TI - Pre mortem analysis of lung injury and lung function in oxygen toxic rabbits. AB - OBJECTIVES: To determine whether respiratory system mechanics measurements could detect lung injury in oxygen toxic rabbits before clinical deterioration. To determine whether respiratory system mechanics measurements, using a power analysis, have the statistical power to detect significant reductions in hyperoxic lung injury due to an intervention when compared with traditional post mortem measurements of lung injury, extravascular lung water, and bronchoalveolar lavage protein concentration. DESIGN: Prospective, controlled study. SETTING: Institutional animal laboratories. SUBJECTS: Adult New Zealand white rabbits. INTERVENTIONS: Spontaneously breathing adult New Zealand white rabbits were exposed continuously to either > 95% oxygen or room air. MEASUREMENTS AND MAIN RESULTS: We measured arterial pH, blood gas tensions, and respiratory system mechanics in rabbits twice, both before exposure to > 95% oxygen, and after the rabbits developed symptoms of mild lung dysfunction. After the second set of respiratory system mechanics measurements, we measured extravascular lung water and bronchoalveolar lavage protein concentration in the hyperoxia-exposed rabbits and compared the values with those values obtained in animals that breathed room air only. Our hyperoxia-exposed rabbits developed symptoms of mild respiratory impairment at 69 +/- 2 hrs. In these hyperoxia-exposed rabbits, measurements of static compliance, quasi-static compliance and resistance all changed significantly (p < .05) when compared with baseline measurements. Functional residual capacity and arterial blood gas values did not change significantly. Furthermore, assuming that an intervention reduced hyperoxic lung injury by a given amount, we performed a power analysis and found that the measurement of static compliance had at least equivalent power to detect a reduction in lung injury from an intervention when compared with measurement of extravascular lung water and bronchoalveolar lavage protein concentration. CONCLUSIONS: Measurements of respiratory system mechanics can detect lung injury in hyperoxic rabbits before the onset of severe clinical deterioration or death. Furthermore, measurement of static compliance of the respiratory system is likely to be a powerful tool to detect a reduction in lung injury produced by an intervention. PMID- 7867359 TI - Effect of tracheal gas insufflation on gas exchange in canine oleic acid-induced lung injury. AB - OBJECTIVE: To determine the effect of tracheal gas insufflation on gas exchange in oleic acid-induced lung injury in dogs. DESIGN: Prospective, longitudinal study. SETTING: University research laboratory. SUBJECTS: Five mongrel dogs. INTERVENTIONS: The dogs were anesthetized, paralyzed, and mechanically ventilated. Lung injury was induced by infusing 0.09 mL/kg of oleic acid and pulmonary artery occlusion (wedge) pressure (PAOP) was increased to 15 mm Hg by infusing fluids to enhance pulmonary edema formation. After 60 mins, PAOP was allowed to decrease to 5 mm Hg and was maintained at 5 mm Hg for 60 mins to stabilize the pulmonary edema. We studied the effect of tracheal gas insufflation on gas exchange at low and high end-expiratory lung volumes achieved by a positive end-expiratory pressure of 5 and 12 cm H2O, respectively. The FIO2 values of the ventilator and catheter were equivalent (0.6). Each tracheal gas insufflation stage at low and high end-expiratory lung volume was preceded and followed by conventional mechanical ventilation stages without tracheal gas insufflation. During transitions between conventional mechanical ventilation and tracheal gas insufflation, end-expiratory lung volume was maintained constant by adjusting positive end-expiratory pressure while monitoring esophageal pressure and inductive plethysmography. Tidal volume was maintained constant throughout the protocol (0.40 L). MEASUREMENTS AND MAIN RESULTS. At end stage, we measured PaCO2, PaO2, total physiologic deadspace fraction, and venous admixture, which were 43 +/- 4 torr (5.7 +/- 0.5 kPa), 325 +/- 6 torr (43.3 +/- 0.8 kPa), 53 +/- 3%, and 4.0 +/- 0.3% before oleic acid lung injury, respectively. After oleic acid injury at low end-expiratory lung volume, these variables were 55 +/- 4 torr (7.3 +/- 0.5 kPa), 73 +/- 13 torr (9.7 +/- 1.7 kPa), 61 +/- 4%, and 50 +/- 7%, respectively. During tracheal gas insufflation at low end-expiratory lung volume conditions, PaCO2 and the total physiologic deadspace fraction decreased significantly (p < .05) to 45 +/- 4 torr (6.0 +/- 0.5 kPa) and 50 +/- 5%, respectively. Under high end-expiratory lung volume conditions, PaCO2 and the total physiologic deadspace fraction were 55 +/- 7 torr (7.3 +/- 0.9 kPa) and 61 +/- 6%, respectively; during tracheal gas insufflation, these variables decreased to 43 +/- 4 torr (5.7 +/- 0.5 kPa) and 52 +/- 5%, respectively (p < .05). Increasing end-expiratory lung volume improved both PaO2 and venous admixture (p < .05) but tracheal gas insufflation had no significant effect on oxygenation efficiency when end-expiratory lung volume was held constant. CONCLUSIONS: Tracheal gas insufflation augmented alveolar ventilation effectively in the setting of oleic acid-induced lung injury in dogs. When end-expiratory lung volume and tidal volume were kept constant, tracheal gas insufflation did not affect oxygenation. PMID- 7867360 TI - Pentoxifylline prevents a decrease in arterial oxygen tension in oleic acid induced lung injury. AB - OBJECTIVES: a) To determine whether pentoxifylline has a preventive effect on the decrease in PaO2 that is caused by oleic acid, and whether pentoxifylline facilitates normalization of PaO2 from the decreased state. b) To examine whether pentoxifylline can attenuate an increase in pulmonary vascular permeability that is induced by oleic acid. DESIGN: Prospective trial. SETTING: University laboratory. SUBJECTS: a) A total of 48 guinea pigs (700 to 1100 g) for blood gas analysis. b) A total of 28 guinea pigs (390 to 670 g) for measurement of pulmonary vascular permeability. INTERVENTIONS: a) For blood gas analysis, the guinea pigs were mechanically ventilated. Oleic acid (15 microL/kg) was injected into the guinea pigs to decrease PaO2. Pentoxifylline (5 or 20 mg/kg) was administered 40 or 3 mins before oleic acid injection or 13 mins after oleic acid injection. b) For measurement of pulmonary vascular permeability, the guinea pigs were anesthetized with pentobarbital and catheterized via the external jugular vein for drug administration. Pentoxifylline (20 mg/kg) plus Evans blue (30 mg/kg) or theophylline (20 mg/kg) plus Evans blue (30 mg/kg) were administered at 40- and 1-min intervals before oleic acid (15 microL/kg) injection, respectively. Perfusion with saline was performed through the aorta 90 mins after the oleic acid injection. The airways were removed and separated into the trachea, the main bronchus, the proximal bronchus, and the distal bronchus. Evans blue was extracted from the airways with formamide for 18 hrs and measured. MEASUREMENTS AND MAIN RESULTS: a) We measured PaO2, PaCO2, and pH, and recorded airway pressure and systemic blood pressure at 15, 10, and 5 mins before oleic acid injection and at 6, 10, 15, 35, 55, and 75 mins after oleic acid injection. Compared with the control groups, a decrease in PaO2 by oleic acid was significantly prevented when pentoxifylline (5 or 20 mg/kg) was administered 40 mins before oleic acid injection. However, a decrease in PaO2 by oleic acid was not significantly reduced when pentoxifylline was administered 3 mins before oleic acid injection. Pentoxifylline administered 13 mins after oleic acid injection did not affect the recovering course of PaO2 significantly. b) An increase in pulmonary vascular permeability by oleic acid was significantly attenuated by both pentoxifylline and theophylline. The effect of theophylline was significantly stronger than the effect of pentoxifylline in the main bronchi. The effect of theophylline was not significantly different from the effect of pentoxifylline in other areas. CONCLUSION: Pentoxifylline is a noteworthy drug that could be a candidate as a therapy to help prevent hypoxemia in lung injuries that share a common mechanism with oleic acid-induced lung injury. PMID- 7867361 TI - Indirect calorimetry in mechanically ventilated children: a new technique that overcomes the problem of endotracheal tube leak. AB - OBJECTIVES: To develop indirect calorimetry to enable measurement of energy expenditure in mechanically ventilated children and to assess the effect of endotracheal tube leak on the accuracy of indirect calorimetry measurements. DESIGN: Prospective, observational study, using a convenience sample. SETTING: Tertiary pediatric intensive care unit in a university-associated children's hospital. PATIENTS: Eighteen patients, 3 months to 10 yrs of age, with various diagnoses, and requiring mechanical ventilation. INTERVENTIONS: Patients were intubated and received routine intensive care treatment. MEASUREMENTS AND MAIN RESULTS: Energy expenditure and respiratory quotient were measured using a new modification to the technique of indirect calorimetry, which includes an assessment of any expired gas lost around the endotracheal tube. Mean energy expenditure was 97% of predicted energy expenditure, but there was great variability between patients, and energy expenditure could not be estimated reliably from predictive equations. The amount of expired gas lost because of gas leak around the endotracheal tube was often a clinically important proportion of total expired gas, and this lost gas could not be predicted by audible endotracheal tube leak. CONCLUSIONS: Measurement of energy expenditure by indirect calorimetry may be useful in the nutritional management of critically ill children. Results may be inaccurate if the gas lost because of leak around uncuffed endotracheal tubes is not taken into account. PMID- 7867362 TI - Respiratory deadspace measurements in neonates with congenital diaphragmatic hernia. AB - OBJECTIVE: To apply the technique of respiratory deadspace measurement to consecutive infants with congenital diaphragmatic hernia, who were referred to our institution, in order to assess the efficiency of gas exchange. DESIGN: A cohort study evaluating the utility of deadspace measurements in neonates with congenital diaphragmatic hernia. SETTING: Tertiary care pediatric intensive care unit in a university hospital. PATIENTS: Thirty infants with congenital diaphragmatic hernia were studied on presentation to our institution, either before the institution of extracorporeal membrane oxygenation (ECMO) or after stabilization on ECMO. METHODS: The CO2 concentration of expired gas sampled at the exhaust port of the test ventilator was continuously measured and transformed to mixed expired CO2 by the following formula that corrects for compressible volume measured by the ventilatory pneumotachometer: mixed expired CO2 = (PCO2 in exhaust gas) x (ventilatory pneumotachometer minute volume)/(minute volume at the proximal airway). We then utilized the Bohr-Enghoff method to calculate the deadspace/tidal volume ratio: deadspace/tidal volume ratio = (PaCO2 - mixed expired PCO2)/PaCO2. MEASUREMENTS AND MAIN RESULTS: Deadspace/tidal volume ratio was calculated either before the institution of ECMO or during temporary separation from ECMO support as the patients demonstrated improvements in gas exchange and lung compliance. One hundred two measurements were made in 30 patients, with a mean of four measurements per patient (range 1 to 10). There was a significant (p = .005) difference between the first deadspace/tidal volume ratio measured, in survivors vs. nonsurvivors. The mean of the highest deadspace/tidal volume ratio in survivors was 0.47 compared with 0.62 in nonsurvivors (p = .003). A deadspace/tidal volume ratio of > or = 0.60 predicted mortality, with a positive predictive value of 80%, a negative predictive value of 79%, and an odds ratio of 15. The mean pre-ECMO deadspace/tidal volume ratio in those infants who ultimately required ECMO was significantly greater than the mean value for infants not requiring ECMO (0.65 vs. 0.43; p = .004). In patients who were treated with ECMO, survivors demonstrated a significant decrease in deadspace/tidal volume ratio during the course of ECMO. This decrease was not seen in the ECMO-treated patients who did not survive. CONCLUSIONS: Predictors of outcome in infants with congenital diaphragmatic hernia have been complicated and contradictory, particularly in the ECMO era. We demonstrated that the respiratory deadspace can be easily quantified in these infants, and that a physiologic deadspace of > 0.60 is associated with a 15-fold increase in mortality rate. We also demonstrated that in those infants treated with ECMO, the survivors manifested a significant decrease in their deadspace/tidal volume ratio before ECMO decannulation. PMID- 7867363 TI - An overview of mortality risk prediction in sepsis. AB - OBJECTIVE: To review the evolution and development of mortality risk prediction methods as they have been applied to the management of septic patients. DATA SOURCES: Selected relevant articles from the pertinent literature. STUDY SELECTION: Theoretical and clinical data on the mortality risk identification, severity of illness scoring systems, and cytokine levels as they relate to mortality in patients with sepsis. DATA EXTRACTION: All concepts relating to mortality risk prediction, cytokines, severity of illness, and intensive care unit (ICU) mortality were explored and interrelated accordingly. DATA SYNTHESIS: In order to improve the precision of the evaluation of new therapies for the treatment of sepsis, to monitor their utilization and to refine their indications, it has been recommended that mortality risk stratification or severity of illness scoring systems be utilized in clinical trials and in practice. With the increasing influence of managed care on healthcare delivery, there will be an increased demand for techniques to stratify patients for cost effective allocation of care. Severity of illness scoring systems are widely utilized for patient stratification in the management of cancer and heart disease. However, the use of such systems in patients with sepsis has been limited to application in clinical trial design for assurance of balance among treatment groups. Mortality risk prediction in sepsis has evolved from identification of risk factors, and simple counts of failing organs, to sophisticated techniques that mathematically transform a raw score, comprised of physiologic and/or clinical data, into a predicted risk of death. Most of the developed systems are based on global ICU populations rather than upon sepsis patient databases. A few, newer systems are derived from such databases. However, the overall discriminating ability of the various methods is similar. Mortality prediction has also been carried out from assessments of endotoxin or cytokine (interleukin-1, interleukin-6, tumor necrosis factor) plasma concentrations. While increased levels of these substances have been correlated with increased mortality, difficulties with bioassay and their sporadic appearance in the bloodstream prevent these measurements from being practically applied. The calibration of risk prediction methods comparing predicted with actual mortality across the breadth of risk for a population of patients is excellent, but overall accuracy in individual patient predictions is such that clinical judgment must remain a major part of decision-making. However, as databases of appropriate patient information increase in size and complexity, it may be possible in the future to devise a scoring system that can be relied on to assist in clinical decision-making. CONCLUSIONS: Severity of illness scoring systems are widely used in critically ill patients. However, their use in patients with sepsis has largely been limited to a means of stratification in clinical trials. As newer sepsis therapies become available, it may be possible to use such systems for refining their indications, and monitoring their utilization. Finally, as the databases supporting the systems increase in size and complexity, it may be possible to utilize them in clinical decision-making. PMID- 7867364 TI - Round table conference on clinical trials for the treatment of sepsis. AB - OBJECTIVES: Using an evidence-based approach for a round table conference, to discuss sepsis according to its current epidemiology and clinical management, lessons which we feel can be learned by investigators from the design and conduct of previous clinical trials of drug therapy, and to describe the "optimum" clinical trials design for treatments of this syndrome. DATA SOURCES: Experts in the field of sepsis were selected and requested to apply an "evidence-based" approach to the published literature, from which recommendations would be synthesized and rated according to levels of evidence. These experts undertook a review of appropriate literature, primarily focusing on evidence presented by clinical trials. Applicable articles were searched for by individual experts, using a variety of on-line search strategies (i.e., MEDLINE, Current Contents; Clinical Medicine). DATA EXTRACTION AND REVIEW: Presentation at the round table conference was followed by agreement by consensus amongst participants as to the grade of recommendation. Individual presentations and arguments for grading of levels of evidence will be published independently. Where possible, recommendations on individual topics were ranked according to the level of evidence presented. Levels I to V were used to rank randomized, controlled trials through case series, respectively. Grade A recommendation is supported by Level I evidence, Grade B recommendation is supported by Level II evidence, and Grade C recommendation is supported by Levels III, IV or V evidence. CONCLUSION: Recommendations for the design, conduct and analysis of future trials of sepsis therapies were summarized. PMID- 7867365 TI - Prolonged pentobarbital and phenobarbital coma for refractory generalized status epilepticus. PMID- 7867366 TI - Fatal metabolic acidosis in a pediatric patient receiving an infusion of propofol in the intensive care unit: is there a relationship? PMID- 7867367 TI - Selective pulmonary suctioning using a tip deflecting wire in mechanically ventilated patients. PMID- 7867368 TI - Prognostic value of the dobutamine test in patients with sepsis syndrome. PMID- 7867369 TI - Management of severe anemia in a pediatric Jehovah's Witness patient. PMID- 7867370 TI - Need for a validated measure of sedating drug efficacy. PMID- 7867371 TI - Release of ATP from cholinergic synaptic vesicles during freeze-thaw cycling. AB - Cholinergic synaptic vesicles were isolated from Torpedo californica and subjected to repeated freeze/thraw (F/T) cycles. Both vesicular (trapped) and released (free) ATP were measured after each cycle. It was found that a constant percentage of vesicular content was released during each F/T cycle. In solutions low in Ca2+ and Mg2+ and high in sucrose, 25% of the ATP is released by each F/T cycle. When synaptic vesicles are resuspended in Tornedo Ringer's (which contains less sucrose, higher Ca2+ and urea), 35-40% of the trapped ATP is released during each F/T cycle. These data contradict the hypothesis that F/T does not disrupt synaptic vesicle membranes (although F/T does disrupt cell membranes and synaptosomes). This nonrupture hypothesis was assumed by C. Solsona, C. Salto, and A. Ymbern (1991, Biochim. Biophys. Acta 1095, 57-62) to calculate cytosolic ATP as 40% of total ATP. Our results indicate that cytosolic ATP is 10-15%. These results may also explain some of the discrepancies in reported values for cytosolic acetylcholine (ACh). Values of 35-50% were obtained by previous workers using the nonrupture hypothesis, and values of 8-22% in experiments that did not depend on the nonrupture hypothesis. Our results refute the nonrupture hypothesis and thus support a lower value for cytosolic ACh. PMID- 7867372 TI - Recognition and management of cardiac arrhythmias. PMID- 7867373 TI - Drug screening for athletes: do the means justify the ends? PMID- 7867374 TI - New developments in developmental dysplasia of the hip. PMID- 7867375 TI - Drug screening in the athletic setting. AB - Considerable energy and money are being spent on drug screening nationally, both in the workplace and the athletic arena. Many legal questions remain unanswered because there are so many different kinds of drug screening programs, and many of the issues have not been tested in court. Unfortunately, there is not a "gold standard" for screening for AOD in student-athletes or in any other setting. The efficacy and detrimental effects of drug screening on student athletes has not been examined in any scientific fashion, and further longitudinal studies are needed to determine efficacy. PMID- 7867376 TI - Gastrointestinal foreign bodies and strictures: radiologic interventions. AB - Food impaction and foreign body ingestion are significant and sometimes life threatening medical problems. As described in part 1 of this monograph, a variety of techniques and instruments are available to diagnose and treat these conditions. The radiologist interested in interventional procedures can find ample opportunities to participate in the management of esophageal obstructions by applying radiographic and fluoroscopic techniques to the diagnosis and removal of foreign bodies and food impactions. The recommended radiologic procedures are relatively safe, cost-effective, and efficient methods of addressing these serious situations. Stricture formation in the gastrointestinal tract is another significant medical problem that can often be managed nonoperatively by the radiologist. Fluoroscopically guided balloon dilatation has become an accepted method of effectively treating a large variety of strictures. As described in part 2 of this article, the technique is easy to perform, usually with very little inconvenience to the patient, and the risks of complications are very low. The procedure is relatively inexpensive and does not require the acquisition of any specialized or high-technology equipment. Also, the technique can be performed easily by any radiologist with interest in interventional procedures on the gut. A wide use of the fluoroscopic methods for treatment of impacted foreign bodies and strictures of the gastrointestinal tract is recommended. PMID- 7867377 TI - A dermatologic diary. Portrait of a practice. PMID- 7867378 TI - Subcutaneous fat necrosis of the newborn. PMID- 7867379 TI - Patch testing in children including early infancy. PMID- 7867380 TI - Spiny keratoderma: case report, classification, and treatment of music box spine dermatoses. AB - The classification of palmoplantar lesions resembling music box spines is confusing, and nearly all attempts at treatment have been futile. We present the case of a 62-year-old white man with symptomatic music box spine lesions on his palms and fingers composed of parakeratotic columns over a hypogranular epidermis. Lesions and symptoms disappeared after a short course of 6 percent salicylic acid gel applied under occlusion. We suggest a classification scheme for this and similar-appearing conditions under the title spiny keratoderma, based on their histologic pattern (parakeratotic or hyperkeratotic) and anatomical location (palmoplantar, diffuse, or associated with epidermal appendages). PMID- 7867381 TI - Chilblain lupus erythematosus (lupus pernio): clinical review of the Mayo Clinic experience and proposal of diagnostic criteria. AB - Five cases of chilblain lupus erythematosus were retrospectively reviewed regarding their clinical, histopathologic, serologic, and immunofluorescence findings. Ages at onset of chilblain lupus erythematosus varied from 26 to 73 years, with a female-to-male ratio of 3:2. Since other entities can be confused with this disorder, we propose the following diagnostic criteria. The two major criteria are skin lesions in acral locations induced by exposure to cold or a drop in temperature, and evidence of lupus erythematosus in the skin lesions by results of histopathologic examination or direct immunofluorescence study. The three minor criteria are coexistence of systemic lupus erythematosus or other skin lesions of discoid lupus erythematosus, response to anti-lupus erythematosus therapy, and negative results of cryoglobulin and cold agglutinin studies. We conclude that chilblain lupus erythematosus can be diagnosed and treated. Discoid lupus erythematosus lesions respond more quickly to treatment than chilblain lupus erythematosus lesions. Treatment with antimalarial agents, prednisone, pentoxifylline, or dapsone was of benefit to our patients. PMID- 7867382 TI - Sunlight and the plant: a toxic combination: severe phytophotodermatitis from Cneoridium dumosum. AB - A severe case of phytophotodermatitis occurred in a patient who had spent several hours walking through an area densely populated with Cneoridium dumosum. This patient's co-worker experienced a similar reaction after undergoing patch testing of an area of skin and exposing it to sunlight. Voluntary patch testing by one of the authors produced a reaction consistent with the other two cases. Approximately twenty other cases were described by a U.S. Fish and Wildlife Service ranger in students who came into contact with the plant during a field trip with him to Baja California, Mexico. Cneoridium dumosum is a common native bush that grows in the chaparral vegetation zone of southern California and Baja California, Mexico. In a search of Poisindex, Medline, Agris International, and Agricola databases, no previous reports of toxic exposures were found. PMID- 7867383 TI - Secondary milia following bullous erysipelas. AB - Secondary milia associated with bullous erysipelas developed in the right leg of a 64-year-old woman. The milia, measuring up to 6 mm, appeared one month after healing of the erysipelas. Findings of histopathologic and immunohistochemical studies showed that the milia were related to dilated eccrine ducts and not to the hair follicle. Topical treatment with 0.05 percent tretinoin cream resulted in almost full resolution of the lesions. PMID- 7867384 TI - A new experimental and clinical approach of combining usage of highly active tumor-infiltrating lymphocytes and highly sensitive antitumor drugs for the advanced malignant tumor. AB - In recent years, tumor-infiltrating lymphocytes (TILs) have been reported to be effective for tumors in experimental and clinical research. In order to increase the therapeutical effect, we modified some steps of Rosenberg's approach: a. cold digestion with collagenase at 4 degrees C for 24 hours; b. sedimentation instead of centrifugation; c. elimination of tumor cells before the cultivation procedure. Compared with the original approach, the proliferation, activity and cytotoxicity of TILs obtained by the modified procedure were much improved. TILs' expansion-fold was greater than that with the original approach. Cytotoxicity against tumor cells was more potent. Increased TILs' subsets were CD3 and CD8 cells. Meanwhile, we took tumor cells from tumor tissues to test their in vitro chemosensitivities to different drugs in order to select highly sensitive antitumor drugs for treatment of cases with advanced tumors. According to the design of using highly active TILs and highly sensitive drugs (H & H therapy), preliminary clinical results of 50 cases showed higher response rates than those in treatment with TIL/IL2, LAK/IL2 and TIL+IL2+CTX. Less toxic side effects were observed in 14 patients. PMID- 7867385 TI - Effect of berberine alone or in combination with argon ion laser treatment on 9L rat glioma cell line. AB - The cell-killing effect and its possible mechanism of berberine used alone or in combination with argon ion laser treatment on 9L rat glioma cells were studied. The survival fraction of 9L cells after single treatment of berberine has been investigated using both colony formation and microtitration (MTT) method, the half lethal dose of berberine (LD50) has been estimated to be 60 micrograms/ml. After the addition of low energy laser treatment, the LD50 of berberine markedly decreased to 10 micrograms/ml. The inhibitory effect of berberine on biosynthesis for DNA, RNA, and protein of 9L cells was enhanced by argon ion laser. Moreover, when morphologic change was examined, the 9L cells showed lysis, encystation, and degeneration after berberine treatment; the laser treatment enhanced the cell killing effect. The study proves the cell-killing effect of berberine combined with laser treatment on 9L rat glioma cell line, hence introducing the possibility of berberine as a photosensitive agent. PMID- 7867386 TI - Influence of iron deficiency on serum IgG subclass and pneumococcal polysaccharides specific IgG subclass antibodies. AB - The serum IgG subclass concentrations in 47 cases and specific IgG subclass antibodies against pneumococcal polysaccharides (PnPs) were measured in 18 cases with iron deficiency. IgG subclass deficiencies were found in 28 (59.6%) cases with the frequency in order as IgG4 (27.7%, 13/47), IgG1 (21.3%, 10/47), IgG3 (14.9%, 7/47), and IgG2 (2.1%, 1/47). Compared with age-matched healthy children, the mean concentration of serum IgG4 and IgG1, and PnPs specific IgG1, IgG2 antibodies were decreased in children with iron deficiency. Decreased CD4+ cells and CD4+/CD8+ ratio in peripheral blood, low interleukin-6 (IL-6) activity, reduced lymphocyte proliferative responsiveness and increased recurrent respiratory tract infections (RRTI) were found in iron deficiency children. These results suggested that serum IgG subclass and PnPs specific IgG subclass antibody deficiencies caused by dysfunction of the regulation of T lymphocyte on B lymphocyte may be related to the susceptibility to RRTI in children with iron deficiency. PMID- 7867387 TI - An investigation of pedigrees of 110 patients with Graves' disease and the clinical significance of determinations of antithyroid antibodies of their first degree relatives. AB - Eight hundred and ten pedigree members of 110 patients with Graves' disease were studied. In 700 first-degree relatives, inquiry of medical history, physical examination (including eyes, thyroid, heart rate, etc), thyroid function tests (serum T3, T4 and TSH levels), determinations of thyroglobulin antibodies (TgAb) and thyroid microsomal antibodies (TmAb) were performed. For male (female) probands, the incidence of Graves' disease in male (female) first-degree relatives were investigated and their serum TgAb and TmAb were analysed. The incidence of these two kinds of autoantibodies in the male (female) first-degree relatives of familial and nonfamilial Graves' disease were analysed. Eighteen persons with positive TgAb and TmAb from 5 pedigrees had been followed up one year after initial determinations. Our results suggest that the positive rates of TgAb and TmAb in the first-degree relatives of Graves' disease were coincident with the incidence of Graves' disease, and the positive results of TgAb and TmAb in the first-degree relatives of Graves' disease may be an indicator of pre Graves' disease or pre-autoimmune thyroid diseases. PMID- 7867388 TI - Inhibition of nitric oxide synthesis increases the secretion of endothelin-1 in vivo and in cultured endothelial cells. AB - The aim of this study is to investigate the effects of nitric oxide, formed from L-arginine, on the production of endothelin-1 in vivo and in cultured endothelial cells. In mechanically ventilated anesthetized dogs (n = 5), mean pulmonary arterial pressure (PAPm) and pulmonary vascular resistance (PVR) during hypoxic ventilation (FIO2 = 0.10) was 25 +/- 3.1 kPa and 68.7 +/- 10.2 kPa.s/L respectively. NG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased the peak value of PAPm and PVR during hypoxic ventilation to 36.6 +/- 4.7 kPa and 158.4 +/- 25 kPa.s/L and its effect lasted for 2-3 hours. Meanwhile, plasma endothelin-1 level in the femoral artery increased by 20.9 +/- 7.1, 25.6 +/- 7.7, 28.6 +/- 7.9 pg/ml at the 60th, 120th, 180th minute after the injection of L-NAME respectively (P < 0.05 vs hypoxic control before the injection). In cultured endothelial cells from umbilical veins, endothelin-1 level of culture medium in control group was 35.1 +/- 5.9 pg/10(5) cells/ml (n = 9). L-NAME increased endothelin-1 level to 42.8 +/- 4.9pg/10(5) cells/ml (n = 9, P < 0.05) in case of 10(-11) mol/L and to 43.0 +/- 4.7 pg/10(5) cells/ml in case of 10(-7) mol/L (n = 9, P < 0.05). These findings indicate that endogenous nitric oxide is an inhibitory modulator of hypoxic pulmonary vasoconstriction and that nitric oxide inhibits the production of endothelin-1 in vivo and in cultured vascular endothelial cells. PMID- 7867389 TI - Functional status of pancreatic islet in acute leukemia. AB - Using enzymatic assay and radioimmunoassay, we studied the functional status of pancreatic islet in 50 patients with acute leukemia. Oral glucose tolerance test and insulin and C peptide release were made in 40 patients before and after treatment. 14 patients who revealed diabetic curve and delayed insulin and C peptide release before treatment showed normal values in 6 after therapy. Five patients with impaired glucose tolerance and decreased insulin and C peptide release before treatment showed normalization of these parameters following therapy. Five patients with normal pretreatment values disclosed abnormal post treatment results. The remaining 16 patients displayed normal results both before and after therapy. Anti-insulin antibodies were negative, and glucagon level was normal in all the 50 patients. The red cell insulin receptor binding rate analysed in 47 patients was significantly higher than in controls (P < 0.001). We considered that the disturbed glucose metabolism in acute leukemia was not uncommon mainly due to the dysfunction of pancreatic islet beta cells as a result of islet damage by leukemic cells, the effect of corticosteroid and chemotherapy and the preexisting diabetes. Impaired glucose metabolism had no influence on therapeutic effect. PMID- 7867390 TI - Anastomotic false aneurysm following abdominal aortic aneurysmectomy and prosthetic grafting. AB - Anastomotic false aneurysm (AFA) of the aorta is a potentially lethal complication after prosthetic grafting. Nineteen aneurysms were encountered in 18 patients within a 30-year period (1960-1991). There were 10 men and 8 women, aged 27-80 years (mean 58 years). In 14 patients, the prostheses were made of silk, in 2 were PTFE, and in 1 each Dacron or silk-Dacron cross-weaved. Patients with an intact AFA had a pulsatile abdominal mass, abdominal pain, an occluded graft and peripheral emboli. Five patients were asymptomatic. Clinical onset of AFA varied from 2 weeks to 12 years (mean 5 years). The accurate rate of diagnosis of single plane angiography was 75% (3 of 4), and computed tomography 100% (ten of ten). Ultrasound was used only once and suggested an AFA. Four AFAs were less than 5cm in diameter. Five patients refused operation and died in 2 years from rupture. Operative mortality was 11% (1 of 9). Treatment was resection of AFA and replacement with a new graft. Life-long follow-up is required for patients with an aortic aneurysm. All ratroperitoneal AFAs should be resected, since the outcome of rupture is poor. PMID- 7867391 TI - Cardiac function and histological changes after non-dynamic cardiomyoplasty and preliminary study of dynamic cardiomyoplasty. AB - By means of histological method and ultrasound cardiographic (UCG) examination, the left-right ratio of transectional area of muscle fiber of latissimus dorsi muscle (LDM) after non-dynamic cardiomyoplasty was 77.4 +/- 11.7% in Group I (3 weeks after operation), and 78.4 +/- 11.6% atrophy and hyperplasia of LDM, but the basical structure was retained. The ejection fraction (EF) decreased significantly after operation (P < 0.05), but the difference between two groups was non- significant. Also, dynamic cardiomyoplasty was performed on a sheep. UCG showed the increased cardiac systolic function after operation. ATPase, succinodehydrogenase (SDH) and PAS examination implied the strengthening of fatigue-resistant ability in skeletal muscles after long-term electrical stimulation. So cardiomyoplasty is suggested to be a supplementary measure in treating end-stage heart failure. PMID- 7867392 TI - A study on acid-base disturbance in patients with post-traumatic multiple organ failure. AB - In order to diagnose accurately the type of acid-base disturbance (ABD) in patients with post-traumatic multiple organ failure (PMOF), arterial blood gases and electrolytes were determined 645 times on 112 patients with PMOF and the data were analyzed with the pre-estimated compensatory formula of ABD and the calculations of anion gap, potential bicarbonate, and blood chlorides. Simple ABD was found in 381 times of determinations and double ABD in 239 when only the formula was used in the analysis, while 264 times of simple ABD, 260 times of double ABD and 96 times of triple ABD were found when the formula was employed in combination with the calculations of anion gap, potential bicarbonate and blood chloride. The mixed types of ABD were increased by 49% (117 times) from 239 to 356 times and triple ABD was increased from 0 to 96 times. The findings indicate that the employment of the combined formula and the calculations of anion gap, potential bicarbonate and blood chloride is of great significance to assess ABD especially its mixed and complicate types in patients with PMOF. It is emphasized that along with the monitoring of blood gases, the determination of blood electrolytes and the calculation of anion gap and potential bicarbonate should be performed to determine the correct type of ABD. PMID- 7867393 TI - Macrophages in degradation of collagen/hydroxylapatite(CHA), beta-tricalcium phosphate ceramics (TCP) artificial bone graft. An in vivo study. AB - The macrophages mediated biodegradation of two biomaterials, collagen/hydroxylapatite (CHA) and beta-tricalcium phosphate ceramics (TCP), was studied in 24 male Kunming mice and 20 male C57BL/6 mice with histopathologic, histochemical and ultrastructural observation. It was demonstrated that macrophages infiltrated after CHA, TCP were implanted. The macrophages could be differentiated from fibroblasts and the other infiltrated cells for special cellular profile and strong acid phosphatase activity. Morphologically, monocyte macrophages and infused multinuclear giant cell degraded CHA and TCP by phagocytosis and extracellular resorption. The carbonic anhydrase activity of macrophages was demonstrated by histochemical technique. It suggested that macrophages secreted H+ and accomplished the decalcification of calcium phosphate compound of CHA and TCP. We conclude that macrophages are the main mediating cells which degraded CHA and TCP intracellularly and extracellularly. PMID- 7867394 TI - Experimental study on hepatic inflow occlusion in rabbits. AB - To evaluate the effect of hepatic inflow occlusion on the liver remnant, three methods of inflow occlusion of the right outside lobe of liver, which was finally resected, were performed in 30 rabbits. The mortality rate of 12 animals (6 in Group I and 6 in Group II) undergone 30 minutes of portal triad clamping (PTC) and selective hepatic artery reserving (SHAR) was both 66.7%. No death occurred in Group III (PTC, n = 6) and IV (SHAR, n = 6) for 20 minutes of hepatic ischemia, but with an irreversible damage to the hepatocytes. The level of serum glutamic-pyruvic transaminase (GPT) in Groups III and IV animals rose to 282.17 U/L and 155.33 U/L on the first postoperative day and thereafter declining slowly to the preoperative level on the 5th and 3rd days, respectively. In Group V with selective hemihepatic vascular occlusion (SHHVO) serum GPT showed only temporary mild rise (112.83 U/L) on the first postoperative day and no hepatic pathologic change appeared. It is obvious that the function of the liver remnant can be best preserved during hepatic resection under SHHVO. PMID- 7867395 TI - Limb-salvage for osteosarcoma. AB - Limb-salvage surgery plays an important role in the treatment of osteosarcoma. Among 104 patients with osteosarcoma we managed from 1974 to 1993, 60 were treated with limb-salvage procedure. 44 patients with IIB tumor received adjuvant chemotherapy, and the five-year survival rate was 46.69%. The local recurrence rate of these 60 patients was 15%, the infection rate 11.7%, and the prosthetic mechanical complication was 13.3%. Our results suggest that limb-salvage procedures are not only possible but also can provide patients with better function. PMID- 7867396 TI - Pathological features of coronary atherosclerotic plaques in nonagenarians. AB - The atherosclerotic lesions from 4 major epicardial coronary arteries (left main, left anterior descending, left circumflex and right coronary arteries) of 23 nonagenarians patients were compared with that from 23 patients aged 60-69. The arteries were cut into transversely 5 mm long segments and were examined by microscope. The inside circumferences of the lumen were measured by computerized morphometric analysis. The results showed that the numbers of atherosclerotic plaques, percentages of narrowing of the coronary arterial lumen and circumferences of the arterial lumen in both groups were similar. But there were much more fibrous and resting (silent) or regressive plaques in the group aged 90 99 years as well as less lipid and active or progressive plaques than those in the group of 60-69 years. The above morphological findings may be correlated with the fact that there was a similar incidence of coronary heart disease but a less risk of acute myocardial infarction in patients aged 90-99 years than those aged 60-69 years. PMID- 7867397 TI - Morphological study of fetal neocortical transplant grafted to the cerebral corresponding area in young rats. Differentiation of immature neurons and reciprocal connections of fibers between graft-host brain. AB - The fetal neocortical transplant (E15-17 days gestation) of Wistar rat was grafted to the corresponding neocortical region (frontal-parietal lobe) of the same strain in young rats (4-5 weeks old). On the 7th, 15th, 30th, 60th, 150th day after transplantation, the sections cut through the middle area of graft-host brain were examined by HE, Nissl, Glees stain, immunohistochemical technique for GFAP and NF, Nissl, Glees stain, immunohistochemical technique for GFAP and NF, acetylcholinesterase (AChE) histochemistry as well as horseradish peroxidase (HRP) retrograde tracing with light microscope. Some of the sections were also examined with TEM. The result showed that most immature neurons within the graft can survive, grow, differentiate and mature, and are similar to the structure of the neocortical neurons of host brain. This study also provides patterns of integration of the interface between graft-host brain varying with the proliferation of reactive astrocyte as well as graft-host reciprocal connection of fibers. PMID- 7867398 TI - Clinical significance of measuring serum IL-6 activities in multiple myeloma. An analysis of 81 cases. PMID- 7867399 TI - Selenium supplement in the prevention of pregnancy induced hypertension. AB - The effect of selenium (Se) supplement on pregnancy was studied in 52 pregnant women with high risk factors of pregnancy induced hypertension (PIH). They were given natural Se dietetic liquid (100 micrograms/d) for 6-8 weeks during late pregnancy, and 48 controls were given placebo. They received similar routine prenatal care. The results revealed that Se supplement on the pregnant women prevented and decreased the incidence of PIH and gestational edema, and elevated the mother's blood Se level by 0.1008 +/- 0.091 ppm in the treated group while decreased by 0.0402 +/- 0.046 ppm in the control group (P < 0.01). The umbilical blood Se level was 0.2756 +/- 0.100 ppm in the treated group and 0.1544 +/- 0.051 ppm in the control (P < 0.01). The differences of the neonatal birth weight and the amount of postpartum hemorrhage between the two groups were not significant. PMID- 7867400 TI - The Sixth National Meeting of the Chinese Society of Hand Surgery. PMID- 7867401 TI - [Quantitative analysis for histochemical grouping of muscle fibers after skeletal muscle transplantation by microneurovascular anastomoses]. AB - A poly-histochemical quantitative assay was carried out on fibers of grafted rectus femoris muscles of rabbit which had undergone simulated free muscle transplantation by microneurovascular anastomoses in speciments at 3, 6, 12 months postoperatively. At the same time, the same assay was done for two experimental control groups: either the motor nerve or the patella tendon was simply severed and immediately sutured. It was found that the contractile characteristics of whole muscle were depended on relative number of different muscle fibers. That meant it was depended on the relative number of different motor fibers which had run through the anastomosed site. The caliber change among different types of muscle fibers mainly represented there was cross reneurotization during nerve regeneration. PMID- 7867402 TI - [The electromandibular kinesiograph in cleft lip and palate with crossbite]. AB - Through the comparative study of 29 unilateral cleft lip and palate patients with crossbite and 29 crossbite patients with MKG we find some features of tracks in the cleft patients as follows: (1) The protrusive distance was larger and the track became less steep; (2) Occlusal interference occurred frequently, the incidence was about 65.5%; (3) The interocclusal rest space was larger; (4) 93.1% of the patients was unilateral mastication, 82.7% of them used the health side. The masticatory tracks were not concentrative and the range of lateral movements in mastication was small; (5) 75.86% of the patients presents one or two kinds of TMJDS symptoms, it should not be overlooked. PMID- 7867403 TI - [The effects of tumor necrosis factor on rabbits' temporomandibular joint]. AB - The histological changes of 16 rabbits' temporomandibular joints (TMJ) were studied after they had been injected with tumor necrosis factor (TNF). The results show that TNF can destroy the articular tissues. The changes are similar to those found in TMJ disturbance syndrome. With the finding that the TNF appears in the synovial fluids of TMJ DS, the authors consider that the changes of articular tissues in TMJ DS are related to the presence of TNF in the joints. PMID- 7867404 TI - [The quantitative study of retentive characteristics and masticatory efficiency of complete overdentures retained by magnetic retainers]. AB - In order to evaluate the role of magnetic retainers for the retention of complete overdentures, the authors applied self-made measuring instrument and absorbent methods to measure the real retentive force and masticatory efficiency quantitatively at pre- and post installation of magnetic retainers in the complete overdentures. The results showed that the retentive force of the denture in the mouth increased about 1500g which was 78.95% measured extraorally; the masticatory efficiency of the patients was 1/3 higher after installation of magnetic retainers in the dentures than before which meant that the denture fitting time of the patient could be shortened. PMID- 7867405 TI - [Nutritional status of patients with oral and maxillofacial malignancies]. PMID- 7867406 TI - [The comparison of three methods for plat castable ceramic crowns]. AB - The adaption of ceramic crown is a critical factor. This study compared the adaption of Plat castable ceramic crowns made by three methods. These are the first, routine method, the second, die spacer technique and the third, model investing method. The average adhesive thickness at different parts of crown of these three crown groups are 157 microns, 65 microns, 41 microns and at the margins are 261 microns, 46 microns, 33.4 microns respectively. The result indicates that the crowns making from the second and third methods could improve the adaption significantly. PMID- 7867407 TI - [High level Le Fort I osteotomy]. PMID- 7867408 TI - [A longitudinal study of tooth exfoliation and dental caries in adults in Gucheng village]. AB - In order to observe the Age-Related changes in dental health conditions, we selected Gucheng village, a rural area of Beijing as a surveillance place for our longitudinal study. 575 persons in different age groups were examined in 1984 and 507 persons were reexamined in 1989. The rate of reexamination was 86.4%. During the 5-year period, 0.3-1.8 teeth were missing in 20-40 years old groups and 2.8 5.5 teeth were missing in 50-70 years old groups. Beyond 60 years old groups more than 43% original remaining teeth were missing or present as residual roots. More than 10% original healthy teeth were decayed and more than 90% original caries teeth became aggravated in elderly group within 5 years. This study indicates that the incidences of tooth mortality and dental caries are much higher in elders than in young adults. PMID- 7867410 TI - [An experimental study of force produced by torquing auxiliary arch in the Begg technique]. PMID- 7867409 TI - [Effects of occlusal splint on postoperative temporomandibular joint: a histopathologic study in monkeys]. PMID- 7867411 TI - [Anatomic study on the relation between temporomandibular joint and middle ear]. PMID- 7867412 TI - [Experiment study of the effect of the low-calcium on the root resorption of orthodontic tooth in the rat]. PMID- 7867413 TI - [Research on malignant changes in oral lichen planus]. PMID- 7867414 TI - [Changes of nasal tip height and alar width following maxillary advancement by Le Fort I osteotomy]. PMID- 7867415 TI - [Changes in dentin permeability induced by medicated dentifrices]. PMID- 7867416 TI - [Cytological study on the effect of fibronectin in promoting periodontal regeneration]. AB - Cell cultures and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] colorimetric assay were used to observe the different biological effects of fibronectin (FN) on periodontal ligament (PDL) cells and gingival fibroblasts (GF). The results showed that FN has the capacity to accelerate PDL cell multiplication at dose 0.044 mumol/L, and accelerate GF multiplication at does from 0.089 mumol/L to 0.178 mumol/L. It suggests that PDL cells are more susceptible to FN than GF. So, the right amount of FN might promote the PDL cells to occupy root surface firstly and multiply, differentiate, and then to form a new connective tissue attachment. PMID- 7867417 TI - [A discussion on prostaglandin E2 levels in gingival crevicular fluid (GCF) and its relation to the periodontitis]. PMID- 7867418 TI - [Removal of intracanal obstructions with ultrasound (an analysis of 206 cases)]. AB - The experience of removing intracanal obstructions with ultrasound in 206 cases from Sept. 1987 to June 1993 was reported. Removal rate was 97.08% (200/206). Six cases failed (2.92%), due to broken endodontic instruments at the apical third or in the curved and fine canals. The success rate of retrieval of casting post-core or other foreign objects was 100%. Our experience proves that ultrasonic technique is more effective and safer than any other methods for removal of intracanal obstructions. PMID- 7867419 TI - [The application of nickel-titanium cone as the solid root canal filling material]. PMID- 7867421 TI - [Therapeutic problem of using enteral nutrition in severe cases]. PMID- 7867420 TI - [Current progress and forecasting of colorectal carcinoma screening]. PMID- 7867422 TI - [A study on the complementary scheme of mass screening for colorectal cancer in an asymptomatic population]. AB - Both SPA immunological fecal occult blood test (SPA FOBT test) and detection of T antigen in rectal mucus (Shams' test) were used as screening tests in asymptomatic mass screening to evaluate the complementary effect of both tests for detection of colorectal cancers. SPA FOBT test showed a positive rate of 11.1% and shams' test 8.9% among 7,740 subjects. In 498 cases with positive screening test, 11 cases of carcinomas and 88 adenomas were found with colonoscopy. Only 9 cancers and 55 adenomas showed positive result in SPA FOBT test and 8 cancers and 51 adenomas in Shams' test. Both tests combined could enhance the detective rate of cancer in asymptomatic mass screening from 81.8% with SPA FOBT test or 72.7% with Shams' test to 90.9%. This complementary effect was more obvious in adenoma detection. It is suggested that there were some shortcomings in sequential FOBT test for cancer detection, the combined use of the two different screening tests for detection of colorectal cancer could decrease the rate of missed detection. PMID- 7867423 TI - [The expression of mutant p53 gene in gastric carcinoma]. AB - Loss or inactivation of p53 gene--a suppressor oncogene has been considered to be one of the important mechanisms in the development of human tumors. One of the evidences for mutation of allelic gene of p53 is the identification of p53 protein concentrated in the nuclei of related cells. By using ABC immunohistochemical method, we studied the expression of p53 in cryostatic sections of the tumor tissue and adjacent mucosa resected from 38 patients with gastric cancer. p53 was found to be positive in the nuclei with intensive staining in 24 out of 38 cases with carcinoma (63.2%). p53 positive cells were distributed diffusively in the cancer tissue. All the adjacent mucosa specimens except 10 were negatively stained with p53 monoclonal antibody. These 10 specimens including 3 with dysplasia and 4 with metaplasia were only weakly stained. p53 was also found to be positive in 18 out of 23 cancer patients with metastasis in perigastric lymph nodes (78.3%). We also studied in the same section the nucleolar organizer region-associated proteins (AgNORs) with using silver staining technique to find if there is any relationship between p53 gene mutation and the activity of rRNA transcription of tumor cells. The number of AgNORs dots per nucleus detected in gastric cancer sections with positive staining of p53 (9.9 + 2.14) was greater than those with p53 negative staining (7.2 + 1.68). There was a significant statistical difference between the two groups (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867424 TI - [Effect of radix Angelicae sinensis on serum gastrin levels in patients with cirrhosis]. AB - Acute and chronic effect of Radix Angelicae Sinensis (RAS) on serum gastrin levels in patients with cirrhosis were investigated. The results showed that after intravenous perfusion of RAS, serum gastrin levels of inferior vana cava, hepatic and peripheral veins were significantly decreased. After long-term administration of the agent, the level fell nearly to that of control subjects. It is suggested that the effect of reducing serum gastrin level by RAS may improve portal hemodynamics and be beneficial for portal hypertensive gastroduodenal mucosal lesions in cirrhosis. PMID- 7867425 TI - [Clinical study of erythromycin action on gallbladder motility in patients with non-ulcer dyspepsia]. AB - Thirty-two patients of non-ulcer dyspepsia (NUD) with gallbladder hypokinesia treated by oral erythromycin administration 0.125g three times daily for two weeks. Before and after oral erythromycin administration, gallbladder volumes were determined by ultrasound, and plasma motilin concentration were determined by radioimmunoassay. The results showed that before and after oral erythromycin administration, maximal percentage emptying of gallbladder were 48.24 +/- 8.30ml vs 69.74 +/- 10.78ml (P < 0.01), plasma motilin were 361.28 +/- 87.92ng/L vs 394.97 +/- 134.27ng/L (P > 0.05). It is indicated that erythromycin could reduce fasting and postprandial residual gallbladder volumes and increases maximal percentage emptying of gallbladder. It suggests that erythromycin might have an agonist action on the motilin receptor as an agonist action on the motilin receptor as an exogenously administrated motilin. PMID- 7867426 TI - [Placement of stent for bile drainage by using combined percutaneous and endoscopic technique]. AB - 44 patients with malignant biliary obstruction underwent attempted placement of stent for bile drainage by using a combined percutaneous transhepatic and endoscopic transpapillary approach (combined procedure). In all the patients endoscopic procedures had failed and there were contraindications for surgery. The initial procedure was percutaneous transhepatic access to the biliary tree. The bile duct was drained externally for three days before the combined procedure. Combined procedure was performed in these 44 cases and successful in 37 (84.1%). The procedure-related morbidity and 30-day mortality were 46.7% and 16.7% respectively for lower common bile duct obstruction and 50.0% and 21.4% for hepatic hilus obstruction. The total morbidity and 30-day mortality were 47.7% and 18.2% respectively. The combined procedure extends the use of endoscopy and offers nonsurgical therapy for patients with malignant biliary obstruction. PMID- 7867427 TI - [Detection of serum anti-histone antibodies in patients with ankylosing spondylitis and its clinical significance]. AB - Serum anti-total and subtypical histone antibodies were detected with ELISA and Western-Blotting in 78 ankylosing spondylitis (AS) and 38 gouty arthritis (GA) patients as well as in 45 normal subjects. The results showed that the positive rate of anti-histone antibodies (AHA) was about 5% in normal subjects or GA patients and 24.4% in AS patients. The mean level of AHAs was much higher in AS group than those in the controls. IgG- and IgM-AHA levels in AS patients during active stage were higher than in those during inactive stage. AHA levels were much more elevated in AS patients with present illness or past history of uveitis than in those without. The high levels of AHAs (especially anti-H3 antibody) were associated with uveitis in AS patients. The results suggested that the high level of AHAs might be a monitoring parameter for disease activity and occurrence of uveitis in patients with AS. PMID- 7867428 TI - [A clinical study of aortic dissecting]. AB - The clinical features, etiologies, pathogenesis, treatment and prognosis of 70 patients with aortic dissecting were studied. Patients with age ranging from 31 to 70 years consisted 93% of the total. The proportion of proximal to distal types is 0.8: 1. Hypertension was present in 67% and Marfan's syndrome 18% of the patients. The pathologic finding was scattered rupture with myxomatous and cystic necrosis of the mecial elastic fibers. 80% of the patients suffered from the disease without any inducing cause. Of the 76% patients had chest pain, it was very severe in 69%. Chest X-ray, ultrasound, computed tomography and magnetic resonance imaging together with clinical manifestations may accurately diagnose the disease. The sensitivity and specificity of the ultrasound are 97% and 94% respectively. The mortality in hospital with surgical and medical therapy of the proximal type was 14% and 22% respectively, while that of the distal type was 63% and 27% respectively. Rupture of the aneurysm was the cause of death in 68% of the patients. PMID- 7867429 TI - [Increased plasma endothelin-1 concentration in acute cerebral infarction and its clinical significance]. AB - In acute cerebral ischemia there are severe damages of endothelium recognized as the stimuli for secretion of endothelin-1, that is a endothelium-derived peptide and seems to be the most potent vasoconstrictor known. The goal of this study is to measure plasma endothelin-1 level in patients with cerebral infarction and determine the relationship between endothelin-1 and ischemic stroke. Plasma level of endothelin-1 was measured in 21 consecutive patients. The measurement was performed 3 times at different stages of stroke. There was a marked increase in plasma endothelin-1 level in the patients and the elevation lasted the entire acute and subacute stage of stroke. There was a correlation between the peptide concentration and infarct volume (r = 0.665, P < 0.01). The result suggests that endothelin-1 plays an important role in the regulation of brain circulation. Apparent and lasting increase in plasma level of endothelin-1 is associated with cerebral ischemia and infarction. The peptide seems to be involved in the pathophysiology of acute cerebral ischemia and have a deleterious effect in the evolution of cerebral infarction. PMID- 7867430 TI - [The hemodynamic and oxygen dynamic effects of mechanical ventilation in chronic cor pulmonale]. AB - Observation by using Swan-Ganz catheter on hemodynamic and oxygen dynamic changes before and after assisted volume controlled mechanical ventilation (MV) was carried out in 11 cases of chronic cor pulmonale complicated with pulmonary encephalopathy. Pulmonary vascular resistance and pulmonary artery pressure were significantly decreased by the relief of hypoxia pulmonary vasoconstriction after MV. Because of the relax of sympathetic tension, the heart rate, arterial blood pressure, pulmonary capillary wedge pressure and central venous pressure reduced simultaneously. Left and right ventricular stroke work decreased after MV, without significant change in cardiac output. Venous admixture (Qs/Qt) was markedly reduced by MV and oxygen supply-demand ratio raised. It is thus shown that marked improvement of hemodynamic and oxygen dynamic status can be induced by mechanical ventilation at an opportune moment. PMID- 7867431 TI - [The diagnosis and management of adrenal "incidentaloma"]. AB - We reported seven patients with adrenal "incidentaloma", diagnosed with ultrasonography and/or computed tomography and confirmed by operation and pathological examination. Three of them were pathologically diagnosed as pheochromocytoma and one each as mixed cell adenoma, bilateral adrenocortical adenoma, leiomyoma and adrenocortical carcinoma. Only one "incidentaloma" had cortisol-secreting function. The diagnosis and management of adrenal "incidentaloma" were discussed. PMID- 7867432 TI - [Long-term culture of normal and leukemia bone marrow cells]. AB - Using long-term bone marrow culture (LTBMC), we studied the in vitro growth status of bone marrow nucleated cells from 5 normal subjects and 14 patients with acute leukemia. The results showed that LTBMC could support normal hematopoiesis selectively, and in the meantime, inhibit the leukemic progenitor growth. Our preliminary clinical application indicated that this culture system could be used to purge the autologous bone marrow graft in vitro for allogeneic bone marrow transplantation. PMID- 7867433 TI - [Transjugular intrahepatic portasystemic stent shunt]. PMID- 7867434 TI - [Control of hospital infection and improvement of quality of medical care]. PMID- 7867435 TI - [Serologic test for syphilis and its clinical significance]. PMID- 7867436 TI - [Clinical evaluation of cefpodoxime proxetil on the treatment of bacterial infections]. AB - 122 patients with bacterial infections of respiratory tract, ear, nose, and throat, urinary tract and skin and soft tissue were treated with cefpodoxime proxetil. In the treatments of patients with clinical efficacy tates of cefpodoxime proxetil for infections in these four systems were 90.0%, 97.5%, 90.0% and 86.4%, respectively. The bacterial clearance rate of gram-positive bacterial was 96.9%, and that of gram-negative bacteria 96.4%. Adverse drug reaction rate was 18.9%. PMID- 7867437 TI - [Clinical efficacy of ciprofloxacin and ofloxacin]. AB - The clinical efficacy, antibacterial activity and adverse effects of ciprofloxacin (CPLX) and ofloxacin (OFLX) produced in our country were compared in five clinical hospital in Beijing and Guangzhou in 1992. Two groups, each consisting of 100 cases, were treated with CPLX and OFLX respectively. The total cure rate was 79% and effective rate 94% after one course of treatment. There was no difference between the two groups (P > 0.05). The positive rate of presence of pathogens was 95% in both groups, but the rate of transformation from positive to negative after one course of treatment was 95.8% (OFLX) and 87.4% (CPLX) respectively. The difference between the two groups was significant (P < 0.05). 99 and 96 strains of bacteria were detected in the CPLX and OFLX group respectively; the elimination rate was 87.9% and 95.8% (P < 0.05). Incidence of adverse effects was 12% (OFLX) and 21% (CPLX) respectively. In a word, both drugs are effective in treating bacterial infections of digestive system, urinary system and respiratory tract. They are safe and reliable. OFLX is better than CPLX in bacteria elimination and incidence of adverse effects. PMID- 7867438 TI - [The pharmacokinetics of ciprofloxacin in patients with renal function of various degrees]. AB - The pharmacokinetics of ciprofloxacin was investigated in 12 patients with renal function of various degrees. A single dose of 500 mg of ciprofloxacin was administered after overnight fasting. Serum and urine samples were collected serially at different intervals and subjected to bioassay and HPLC. Pharmacokinetic parameters were analyzed by assuming an open two-compartment model. Apparent difference was observed in pharmacokinetic parameters between patients with severe impairment of renal function and those with normal renal function. For the former group, the area under the curve of serum concentration versus time was tripled (42.22 +/- 12.48 vs. 14.55 +/- 6.66 mg.h-1.ml-1, the renal clearance of ciprofloxacin was reduced to one-tenth (22.43 +/- 12.08 vs. 193.13 +/- 65.14 ml/min), and the elimination half-life was prolonged twofold (9.28 +/- 2.42 vs. 4.72 +/- 1.35 h). The correlation between renal drug clearance and Ccr was highly significant (r = 0.935, P < 0.001). On the basis of these findings, it is suggested that a reduction of one half of the dose of ciprofloxacin or an increase of a double of the administration time interval may be indicated in chronic renal failure with GFR less than 25 ml/min. PMID- 7867439 TI - [A clinicopathological analysis of 70 cases of liver alveolar echinococcosis with a comment of the prognostic factors]. AB - As to the geographical distribution of the 70 cases of liver alveolar echinococcosis in the present series, the highest incidence was found in Gansu province (82.8%), where most of the patients came from Zhang county (65.6%). Female outnumbered slightly male. Most patients were young and in robust years of their life (98.8%). The most frequent symptom was liver mass (56.4%) and the next abdominal pain (28.2%). Imaging examination and immunological test were helpful to the diagnosis. Under microscopic observation the hyperplastic bud from germinal membrane of liver alveococcus cyst wall comprised a few nuclei and showed exogenous or endogenous budding. According to whether alveococcus proliferation was present or not, pathological types of regressive grade I and hyperplastic grade II were discerned. Resection was not done in 34 cases during exploratory laparotomy, but drainage was performed in 8 cases for alveococcus necrotic pseudocyst and cholecstostomy was done in one case for jaundice. Albendazole or/and traditional Chinese medicine were administered in 35 cases. The prognosis of the patients in relevant to some factors such as sex, age, pathology, symptom and treatment was discussed. PMID- 7867440 TI - [A study of captopril enhancement of nitrate effect coronary arterial disease patients associated with heart failure]. AB - It is shown in a prospective study that the initial beneficial hemodynamic effect of nitroglycerine (NTG) significantly decreased after continuous 3-day infusion of this drug (10-50 micrograms/min) in acute myocardial infarction (AMI) patients associated with acute left heart failure. The effect of ameliorating anginapectoris and improving heart function with isosorbide dinitrate (ISDN) gradually decreased almost to pretreatment levels after oral administration of this drug (10-20mg, 4 times daily) for 3 weeks in anginapectoris patients associated with congestive heart failure (CHF) with accompanying increased level of plasma angiotensin II (AII) and body weight. However, when captopril (CPT, 12.5-25mg, 3 times daily) was combined with nitrates, the clinical effects were enhanced and maintained throughout the study, along with a decrease in the level of AII and body weight. In the hearts of rats perfused with CPT and NTG, the coronary flow (CF) significantly increased as compared with the flow when either drug was used alone. Enelapril (ENL, a non-sulfhydryl drug), however, did not show such effect. The above results indicate that repletion of sulfhydryl to vascular smooth muscle and antineurohumoral activation may be the potential mechanisms by which CPT reverses nitrate tolerance and enhances its clinical effects. PMID- 7867441 TI - [Helicobacter pylori in the dental plaque]. AB - Helicobacter pylori (Hp) were detected in the dental plaque in 40 patients with peptic ulcer, chronic gastritis or gastric cancer with rapid urease test, anti-Hp fluorescein-labelled antibody staining, bacterial culture and electronic microscopy. At the same time, biopsy specimens from the gastric antrum of these patients were studied with WS staining and rapid urease test to detect Hp. The results show that a great lot of Hps is present in most of the patients' dental plaque. The morphological, biochemical and immunological characteristics of the Hp in the dental plaque are similar to those Hp in the gastric mucosa. The above results reveal that the Hp in the dental plaque may be identical with those in the stomach. PMID- 7867442 TI - [Non-surgical treatment of small cell lung cancer with chemo-radio-immunotherapy and traditional Chinese medicine]. AB - 54 consecutive cases of small cell lung cancer (SCLC) were treated with longterm short-interval combined treatment modalities of chemotherapy, radiotherapy (55-65 GY), immunotherapy, traditional Chinese medicine (leaf of Asiatic Ginseng, root of Astragalus membranaceus Bge, etc) and other adjuvants. Chemotherapy consisted of vincristine, cyclophosphamide, methotrexate and carmustine. A complete response of 59.2%, partial response of 38.9% and an overall response of 98.1% were achieved. According to Kaplan-Meier, the survival rates of SCLC with limited disease for 1, 3, 5 and 10 years were 78.1%, 42.6%, 32.1% and 21.4% respectively; while those with extensive disease for 1, 3, and 5 years 90.5%, 13.4% and 13.4%. According to classification of international TNM staging (1988), the survival rates of stage II SCLC for 1, 3, 5 and 10 years were 92.9%, 61.9%, 53.1% and 31.8% respectively; of stage IIIa for 1, 3 and 5 years 80.0%, 30.0% and 20.0%, and of stage IIIb 83.3%, 20.8% and 15.6%. Our combined modalities raised the survival rates considerably; the improved effect was mainly due to the long-term (especially more than 2 years or 10 courses), short-interval, effective and timely combined treatment with chemotherapy, radiotherapy and adjuvants such as traditional Chinese medicine and immunotherapy. By using the above therapeutic strategy, 10 out of 12 SCLC patients including 4 with extensive disease, who were relatives of our hospital staffs, have gained more than 3-17 years of survival. Therefore small cell lung cancer even with extensive disease was a hopeful curable disease. PMID- 7867443 TI - [The relationship between the plasma levels of endothelin and angiopathy in diabetic patients]. AB - Plasma levels of endothelin (ET), vasoconstrictor peptide released from vascular endothelial cells, have been measured by radioimmunoassay in 48 patients with NIDDM and 20 healthy subjects. The plasma ET concentrations were found to be greatly elevated in the patients with diabetes compared with the healthy subjects (P < 0.001). We also find that the plasma levels of ET were higher in diabetic patients with complication of diabetes mellitus than in those without complication (P < 0.02). The elevated ET levels were related to hypertension and/or diabetic angiopathy. There were no significant correlations between plasma ET concentrations and blood glucose, HbA1 et al. In diabetic patients elevated ET levels may play a pathophysiological role in the development of diabetic complication. PMID- 7867444 TI - [High-dose cytarabine as intensive postremission therapy in acute myelogenous leukemia: effect on long-term disease-free survival]. AB - In an attempt to increase the proportion of patients with acute myelogenous leukemia (AML) remaining in long-term disease-free survival (DFS). 37 patients with AML in complete remission (CR) received HD-Ara-C (1.0 g/m2) as intensive postremission therapy. The results were compared with those of 28 patients who did not receive HD-Ara-C therapy (control group) during the same period. With a median follow-up of 21.7 months (6.9-77.3), median CR duration was 16.0 months for HD-Ara-C group and 10.0 months (2.0-75.2) for the control group. Relapse rates were 48.6% (18/37) and 75% (21/28), respectively. The actuarial 3 and 5 years DFS was 50.2% and 43% for HD-Ara-C group versus 31% and 16.7% for the control group. There was significant difference (P < 0.05). This result suggested that HD-Ara-C could prolong DFS and reduce relapse in patients with AML. PMID- 7867445 TI - [Vascular parkinsonism: verified clinicopathological correlation in a case]. AB - Classifications of Parkinsonism in the past have induced an "arteriosclerotic" variety and vascular etiology has thus been proposed. However, controversy exists whether such an entity actually exists, because there has not been a single pathologically verified case with adequate clinical correlation. We report a case with clinical syndrome indistinguishable from Parkinson disease and postmortem examination revealing extensive lacunar infarction of the basal ganglia without evidence of coexistent Parkinson disease. This case provides pathologic confirmation for the concept of vascular Parkinsonism. PMID- 7867446 TI - [Microsporidium and microsporidiosis]. PMID- 7867447 TI - [Determination of urine iodine in school children in iodine deficiency disorders areas]. AB - Twenty-four-hour urine iodine and afternoon casual urine iodine were determined in children aged 7-14 years grouped into A, B, C, and D at two-year interval in the areas where iodized salt prophylaxis had been instituted. Results showed there was no significant difference between urine iodine values expressed in median of microgram/g Cr x creatinine coefficient and in microgram/24 hr, and the former was considered to reflect the real iodine value in urine. Urine iodine in children of groups C and D (older) was greater than of A and B (younger). Urine iodine reached the lower limit only in 51.2% of the children aged 13-14 years in Heba Township where iodized salt prophylaxis was instituted, with 75 micrograms iodine intake daily as lower limit. It suggested iodine deficiency remained a problem in that area. PMID- 7867448 TI - [Effects of iodine nutritional status of fetuses, infants and young children on their intelligence development in the areas with iodine-deficiency disorders]. AB - Intelligence in children without iodine supplement during their fetal and infant periods, and in those born three to four years after the implementation of stable supply of iodized salt in the areas with endemic cretinism and goiter was tested with Standord-Binet method. Results indicated there existed a lot of mental retarded children in the iodine-deficiency areas, with most of them born before the implementation of iodine supplement. In order to study the changes of intelligence development in children probably induced by stable supply with iodine, the tested children living in the areas with endemic cretinism were followed-up for two years, and no improvement in children's intelligence could been seen. It suggested that impairment to children's intelligence development caused by iodine deficiency during their fetal and infant periods was irreversible. PMID- 7867449 TI - [Effects of thioglucoside on thyroid and iodine metabolism]. AB - Swine, fed with fodder containing 8%-16% rape-seed meal, took 919.42-1416.02 mg of thioglucoside (glucosinolate) daily. After being fed with it for 120 consecutive days, swine's thyroid enlarged and their thyroid follicles and epithelial cells were prominently hyperplastic, lacking secretory granules and lysosome in thyroid cytoplasm, with microvilli condensed in apical cells, and a great number of vacuoles surrounding the colloid in the follicular cavity, with its secretory function vigorous and significantly increased T4 and ratio of T4 to T3, and showing hyperthyroidism. If iodine was supplied in the fodder and the antidotes were administered, the morphology and ultrastructure of the thyroid tissues in swine restored to normal, and their T4 and ratio of T4 to T3 tended to be normal, too. PMID- 7867450 TI - [Analysis of spatial clustering of disease]. AB - It is difficult to determine whether there is spatial clustering of disease if the geographical distribution of population is unknown. Permutation test reported in the paper can be used as a method to judge the spatial clustering with unknown distribution of a random sample of cases. Comparison of difference in frequency of small distances between pairs of cases and controls can show whether there is spatial clustering of the disease. PMID- 7867451 TI - [Factors affecting young children's mental development and their significance in intervention]. AB - Factors affecting their developmental quotients (DQ) in 48 normal young children, who were involved in regular development assessments at child health care outpatient visits and whose parents received child-rearing guidance at Chaoyangmen Subdistrict of Dongcheng District, Beijing, and 43 controls aged 36 months were analyzed. Factors, such as their parents' receiving child-rearing guidance, paternal education, maternal education, paternal occupation, type of nursery schools, home environment quality score (HEQS) at 24 and 36 months of age, and mothers' knowledge of child-rearing were associated with children's DQ at their age of 36 months, with statistical significance at a level of 0.05 in univariate analysis. With multiple regression analysis, HEQS at the age of 36 months, family size at the age of 24 months, paternal education, children's sex, and mothers' age had influences on DQ at age of 36 months with statistical significance, and the degree of correlation of HEQS with DQ at 36 months was much higher than that of other factors, and it suggested that HEQS was an important link in child developmental intervention. PMID- 7867452 TI - [Multivariate analysis of relationship between breast feeding and infant physical development]. AB - Longitudinal analysis with generalized estimating equation (GEE) revealed breast feeding can promote infant physical development and growth, and cross-sectional analysis with canonical correlation showed protein intake with breast milk as its main source brought about infants to develop physically tall and lean at first, which might support the theory that protein intake affects more on their development and growth. The extent of infant physical development and growth varied with the amount of breast milk of his or her mother, which should be caught attention in comparison of infant physical development with different feeding patterns. It is suggested that intervention of breast feeding should be implemented during perinatal period and 1-2 months after delivery with emphasis on health education. PMID- 7867453 TI - [Effects of chrysotile on the conformation of membrane protein and the antagonistic action of aluminum citrate]. AB - Effects of Mangai and Laiyuan chrysotile on the conformation of membrane protein and the antagonistic action of aluminum citrate to them were studied with circular dichroism. Results showed that these two kinds of chrysotile could significantly reduce the amount of alpha-helix in membrane protein of human erythrocytes in 20 minutes with a dose-dependent manner. Effect of Mangai chrysotile was stronger than that of Laiyuan one. It suggested the changes in the conformation of membrane protein were the key link in chrysotile-caused hemolysis. After treatment with aluminum citrate, these effects weakened. It provided important information for elucidating the mechanism of aluminum citrate in antagonism to cytotoxicity of chrysotile. PMID- 7867454 TI - [An epidemiological study on malaria infection in plasmapheresis donors]. AB - Epidemiological studies showed incidence of malaria in 8391 plasmapheresis donors of five villages was 4.14%, higher than in those donating whole blood and non- donors. Case--control studies revealed plasmapheresis was a risk factor for malaria infection. Incubation period of plasmapheresis--associated malaria was 16.5 days. Investigation on the blood bank showed there existed cross infection in plasmapheresis. After the close of the blood bank, epidemic of malaria caused by cross infection in plasmapheresis was under control. PMID- 7867455 TI - [Risk analysis of combination effects of risk factors for primary liver cancer]. AB - Combination effects of major risk factors for primary liver cancer (PLC) was evaluated by generalized relative risk model to examine the adequacy of the multiplicative structure for describing the effects of them and to estimate their relative risk (RR) and population attributable risk (PAR). The results suggested combination effects of hepatitis B virus (HBV) infection and drinking pond-ditch water tended to be multiplicative, and that of aflatoxin B1 (AFB1) contamination and HBV infection and drinking pond-ditch water to be additive. The relative importance of these factors of PLC based on their RR and PAR was HBV infection, drinking pond-ditch water, and AFB1 contamination in proper order. Recognition of the mode of the combination effects of relevant risk factors was important for the causal explanation and public health practice. PMID- 7867456 TI - [Determination of finger vibrotactile threshold and its significance in patients with hand-arm vibration syndrome]. AB - Vibrotactile sense threshold (VST) of the end of the middle fingers in 97 patients with established or suspected hand-arm vibration syndrome and 60 healthy controls was determined, and finger VST contour and vibration damage curve were plotted. Results revealed the most sensitive frequencies of VST were 8 Hz for the patients and 125 Hz for the controls, respectively. VST in the patients with hand arm vibration syndrome was higher than that in the controls, and the threshold shift was initially at high frequency with a "V" dip at 125 Hz and 250 Hz. So, the authors think determination of VST is an auxiliary method used for diagnosis of hand-arm vibration syndrome. PMID- 7867457 TI - [Effects of pollution with fluoride on bone dynamics of periosteum in iliac of domestic pigs]. AB - Studies on bone dynamic parameters of iliac periosteum and endosteum in domestic pigs with fluorosis caused by coal-burning contamination were conducted. Bone dynamics of 12 pigs with experimental fluorosis and nine controls both labelled with double tetracycline was investigated. Results showed the distance between two labels on iliac periosteum of domestic pigs with fluorosis shortened and, rates of mineralization and bone matrix formation slowed. It suggested fluorosis played significantly inhibitory roles in bone formation on the periosteal membrane of pig iliac. PMID- 7867458 TI - [Evaluation of health promotive effect of organometallic germanium compounds]. PMID- 7867459 TI - The consequences of public disclosure: an opinion from Newport Hospital, Newport, Rhode Island. PMID- 7867460 TI - Litigation cells: definition and observations on a cell type in cervical vaginal smears not addressed by the Bethesda System. PMID- 7867461 TI - In search of a "reasonable person standard" for gynecologic cytologists. PMID- 7867462 TI - Cytopathology: negligence and a lawyer's opinion. PMID- 7867463 TI - Morphologic and morphometric features of low grade serous tumours of the ovary. AB - Peritoneal washings from twelve patients with serous tumours of the ovary were studied. Six patients had borderline serous tumours (BSTs), and six had grade one adenocarcinomas. Papanicolaou stained slides were assessed for nine morphologic parameters; background, single cells, size of papillary fragments, contour of papillary fragments, psamomma bodies, cytoplasmic vacuoles, nuclear pleomorphism, nuclear membrane contour, and nucleoli. The slides were destained and restained by the Feulgen method for assessment, with a computer based image analysis system (CAS100, Cell Analysis Systems, Inc., Elmhurst, IL), of DNA content, nuclear size, and nuclear roundness. The contour of the papillary fragments (P = 0.004) and the presence of nuclear pleomorphism (0.019) were distinguishing characteristics. All six BSTs were diploid while three of the six adenocarcinomas had aneuploidy. Two exhibited polyploid DNA distribution and one exhibited diploid DNA distribution. The pooled data for the nuclear size and roundness showed little difference in the modal values, although the nuclei of the adenocarcinoma cells were slightly larger than those of the borderline cells (54 sq. microns vs. 46 sw. microns). However, the coefficients of variation (CVs) for each of these parameters were larger in the adenocarcinoma group than in the borderline group (59.7 vs. 36.4% for size and 33.5 vs. 17.8% for roundness). Although the sample size is small, the data suggest that aneuploidy is rare in borderline tumours. In addition, the presence of papillary groups with irregular contours and nuclear pleomorphism (reflected in higher CVs for nuclear size and roundness) both occur more commonly in adenocarcinomas than in borderline tumours and may be of predictive value in distinguishing the two groups. PMID- 7867464 TI - Postmenopausal squamous-cell atypias: a diagnostic challenge. AB - Exfoliative cytologic studies directed toward atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) have been neglected in the rising postmenopausal population. This retrospective study from 60 cases, initially interpreted as ASCUS or LSIL, concentrates on these lesions and their associated diagnostic pitfalls. Cytologic reevaluation of the 60 patients revealed squamous-cell abnormalities in 45 (18 ASCUS and 27 LSIL) and cervicitis alone in 15 cases. Follow-up studies of the 18 ASCUS cases showed cervicitis in seven, persistent ASCUS in five, CIN I in five, and VAIN I-II in one. Follow-up of the 27 cases categorized as LSIL, showed ASCUS in two, CIN in 20 and VAIN in one, while four had cervicitis alone. Interestingly, two of these 45 patients had only vaginal dysplasia. By application of uniform diagnostic criteria, 15 of the 60 cases were reviewed as benign. Pitfalls included inflammatory and drying alterations, reactive metaplasia, and sampling problems. Thus, squamous-cell abnormalities in postmenopausal women can be significant when artifactual alterations are eliminated. PMID- 7867465 TI - Fine-needle aspiration biopsy of childhood rhabdomyosarcoma: reevaluation of the cytologic criteria for diagnosis. AB - The distinction between rhabdomyosarcoma (RMS) and the other small round blue cell tumors of childhood has therapeutic implications which stress the importance of a correct diagnosis. In attempts to reevaluate the cytologic criteria of this entity, we reviewed a series of 17 fine-needle aspiration biopsies and three touch imprints from soft tissue masses. All cases had been histologically confirmed except for two cases that only had immunocytochemical and ultrastructural confirmation. The features occurring most commonly include a uniform population of tumor cells arranged as single cells and cohesive aggregates. The cells were predominantly round/polygonal, with uniform nuclei and scant to moderate amounts of cytoplasm. The nuclear chromatin was most often finely granular and hyperchromatic, while nucleoli were inconspicuous. Binucleated and multinucleated cells were found in 17 of the 20 smears. Intracytoplasmic vacuoles were present in 17 cases, ranging from occasional in one case, a few in 10 cases, and very numerous in six cases. We conclude that the presence of bi/multinucleated cells is an important clue for the diagnosis of RMS on fine-needle aspiration biopsy. PMID- 7867466 TI - Application of impression cytology to the diagnosis of conjunctival neoplasms. AB - Conjunctival impression cytology using cellulose acetate filter paper was employed to obtain multiple samples of conjunctival epithelium from 192 normal and abnormal eyes. Modifications of an established technique were used and the impressions were stained by the Papanicolaou method and mounted on glass slides. The impressions were examined for their effectiveness in demonstrating the morphological characteristics of normal epithelium and the features of the more common conjunctival neoplasms. The technique was found to be successful at both removing cells and preserving cytologic features. It also had several advantages over other collection techniques. Overlapping cells were not a detrimental feature of the preparations from this study. PMID- 7867467 TI - Immunocytochemical staining of c-erb B-2 oncogene in fine-needle aspirates of breast carcinoma: a comparison with tissue sections and other breast cancer prognostic factors. AB - The role of fine-needle aspiration (FNA) in breast cancer management is expanding to include prognostic in addition to diagnostic studies. This study was undertaken to compare the immunohistochemical staining of c-erbB-2, a breast cancer prognostic factor, on cytologic FNA smears of breast cancer with that on corresponding formalin-fixed, paraffin-embedded tissue sections of the same tumor and to correlate the c-erbB-2 expression with other known breast cancer prognostic factors. FNA smears (destained, alcohol-fixed, Pap-stained direct smears) and corresponding tissue sections (formalin-fixed, paraffin-embedded, unstained sections) from 36 primary breast carcinomas were stained immunohistochemically with c-erbB-2 antibody using an avidin-biotin procedure. Ten tumors (28%) showed strong positive staining for c-erbB-2 on the FNA smear and, of those ten, seven were positive on the corresponding tissue section and three were negative. In several of the cytology and tissue positive cases, staining on the tissue section was significantly weaker than on the FNA smear. Two cases involved treatment with preoperative chemotherapy; in one of those cases, tissue staining was weaker than cytologic staining, and, in the other case, both were negative. Correlation of c-erbB-2 staining with other prognostic factors showed an association between positive c-erbB-2 staining and high nuclear grade. Our results indicate that immunohistochemical staining for c-erbB-2 can be performed on destained FNA smears of breast carcinomas and may be more sensitive on the cytologic specimens than on formalin-fixed, paraffin-embedded tissue sections. PMID- 7867468 TI - Diagnosing intramuscular myxoma by fine-needle aspiration: a multidisciplinary approach. AB - The gross and microscopic appearances of aspirates from ten intramuscular myxomas are reported. The specimens were obtained from seven women and three men, ages 43 to 75, who had tumors involving the muscles of the thigh (7), upper arm (2), and forearm (1). Magnetic resonance (MR) imaging performed in six of the ten cases revealed well-defined, sharply demarcated tumors exhibiting low signal intensity relative to muscle on the T1-weighted images. The tumors were hyperintense to muscle on T2-weighted images. All aspirated tissues were clear, tenacious, and viscous. Smears contained few spindled and histiocytoid cells in an abundant mucoid background. Spindle cells demonstrated long cytoplasmic processes that in areas intertwined to form fibrillar tangles. Nuclei were oval to spindled with fine chromatin and inconspicuous nucleoli. Capillaries were sparse with simple (non-plexiform) branching. The differential diagnosis of myxoid lesions of the extremities includes benign entities such as myxoid schwannoma and neurofibroma, mesenchymal repair, and ganglion cyst, as well as malignant neoplasms such as myxoid liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, and extraskeletal chondrosarcoma. The findings of this study revealed that, although the cytologic features were suggestive of intramuscular myxoma, a definitive diagnosis was often difficult, owing to scant cellularity and lack of distinctive cytologic features. The MR imaging findings may be utilized as an adjunct to the cytologic features to more confidently suggest a diagnosis of intramuscular myxoma. PMID- 7867469 TI - Retrospective c-erbB-2 immunostaining in aspiration cytology of breast cancer. AB - Fifty fine-needle aspiration cytologies of breast that were diagnosed as carcinomas were retrieved from the files and retrospectively evaluated for the expression of c-erbB-2 oncoprotein using standard immunocytochemical methods. Corresponding histologic sections of all tumors were similarly studied. Seventeen fine-needle aspirates (34%) reacted positively for the presence of c-erbB-2 oncoprotein. All but one (32%) of the corresponding tissue sections were also positive for c-erbB-2 by immunohistochemistry. All positive cases were infiltrative ductal carcinomas with a preponderance of the comedo type. Positive reactions were localized in the cytoplasmic membrane of tumor cells. The staining was either present in all cells throughout a tumor, or it was completely absent. We conclude that immunocytochemistry for c-erbB-2 oncoprotein can be performed on fine-needle aspiration cytology samples that are previously fixed and stained with the Papanicolaou technique. Furthermore, the sensitivity of immunostaining results are comparable to that obtained in histologic sections. PMID- 7867470 TI - Small-cell carcinoma of the ovary in peritoneal fluid. AB - Two cases of small-cell carcinoma of the ovary in the ascitic fluid and peritoneal/pelvic washings of a 30- and 28-yr-old woman, respectively, are presented and discussed. Smear preparations from the ascitic fluid showed loose clusters and single malignant cells with scant cytoplasm and nuclei with smooth to irregular nuclear membranes, granular chromatin, and small nucleoli. In the second case peritoneal/pelvic washing specimens contained clusters and single malignant cells with a moderate amount of cytoplasm and nuclei with smooth nuclear membranes, granular, clumped chromatin, and prominent nucleoli. Hisology confirmed the diagnosis of small-cell carcinoma of the ovary. These are the first reported cases of this rare ovarian neoplasm present on fluid cytology. Its differentiation from other small-cell neoplasms on peritoneal fluid cytology from young women is discussed. PMID- 7867471 TI - Fine-needle aspiration biopsy diagnosis of extrarenal malignant rhabdoid tumor. AB - Two cases of extrarenal malignant rhabdoid tumors are presented in which diagnosis was suggested by fine-needle aspiration biopsy and confirmed by histologic and electron microscopic examination. Fine-needle aspiration smears in both cases revealed round to polygonal cells with vesicular nuclei and prominent nucleoli. Several tumor cells contained cytoplasmic inclusions composed of intermediate filaments. A majority of the tumor cells stained strongly for vimentin and cytokeratin. Electron microscopic examination revealed many cells with large aggregates of intermediate filaments corresponding to the cytoplasmic inclusions. Fine-needle aspiration biopsy may be used for diagnosing malignant rhabdoid tumor. The diagnosis may be further confirmed by immunohistochemistry and electron microscopy. PMID- 7867472 TI - Metastatic medullary thyroid carcinoma in liver diagnosis by aspiration cytology. AB - A case of metastatic medullary thyroid carcinoma (MTC) to the liver of a patient with multiple endocrine neoplasia (MEN) Type IIb was suggested by percutaneous fine-needle aspiration cytology and confirmed by histology and immunohistochemistry. The cytologic presentation of this unusual thyroid cancer in liver has not been previously reported. We report such a case and discuss its differential diagnosis from other metastatic tumors of the liver. PMID- 7867473 TI - Ultrasonically guided fine-needle aspiration biopsy of portal vein thrombosis: a cytomorphological study of 14 patients. AB - Portal vein tumor thrombosis is an important and consistent prognostic indicator in hepatocellular carcinoma. We reviewed 14 cases of ultrasonically guided fine needle aspiration biopsy (FNAB) of the portal vein. All the patients had clinical evidence of portal vein thrombosis (PVT). Twelve of these patients had a preliminary diagnosis of hepatocellular carcinoma while the remaining two, initially, had a clinical diagnosis of end-stage liver disease. The mean age of the patients was 60 years. An average of 1.7 passes per case was made. No clinical complications were encountered. The cytomorphologic features of the aspirated materials were reviewed. Twelve of the 14 cases (85.7%) were judged neoplastic or thought to have probable neoplastic involvement of the portal vein while two were clearly benign. The cell block was found to be the most useful in diagnosis. We conclude that FNAB of the portal vein is a feasible method in evaluating PVT, especially in patients already known to have hepatocellular carcinoma. PMID- 7867474 TI - Fine-needle aspiration biopsy of salivary gland mycoses. AB - This report details the fine-needle aspiration biopsy (FNAB) cytomorphologic features of two cases of salivary gland mycosis. Both patients had acquired immunodeficiency syndrome (AIDS) and presented with parotid gland masses. The first patient had Histoplasmosis with secondary infection by Candida. Cytopathologically, the FNAB smears showed classic features of a deep-seated mycosis characterized by necrosis and scattered fungal forms. The second patient had a colonizing sialadenitis caused by either Asperigillus or Fusarium. Cytopathologically, the findings were similar to those seen in aspergillomas of the lung or paranasal sinuses with numerous hyphal forms and an absence of an inflammatory response. Because mycotic disease can induce a wide spectrum of pathogenic change, other benign or malignant, solid or cystic lesions enter into the differential diagnosis. PMID- 7867475 TI - Melanocytic schwannoma: the cytologic aspect in fine-needle aspiration cytology (FNAC): report of a case located in the spinal cord. AB - We describe a case of intramedullary melanocytic schwannoma (MS) studied by means of fine-needle aspiration cytology (FNAC). The main cytologic features were (1) large three-dimensional clusters overshadowed by heavy pigment deposits which tested positive for Fontana Masson (and bleached with potassium permanganate), HMB-45, Vimentin, and S-100 protein; (2) loose syncytial monolayered sheets with very little pigment deposit; and (3) isolated spindle cells with polarized nucleus and tapered, thin cytoplasmic ends. Both the cytologic features and the immunophenotypic profile were nonspecific and on their own were insufficient to allow the diagnosis of MS to be reached. Clinical data and the magnetic resonance image (MRI) in conjunction with the cytologic findings did suggest the diagnosis of intramedullary MS. PMID- 7867476 TI - Pitfalls in the cytologic diagnosis of angiosarcoma of the breast by fine-needle aspiration: a case report. AB - This paper describes a case of angiosarcoma of the breast in a 26-yr-old female. The tumor, originally thought to be granulation tissue on fine-needle aspiration biopsy, was correctly identified as a malignant neoplasm of probable mesenchymal origin on a repeat FNA biopsy 4 mo later. A diagnosis of angiosarcoma was made on a subsequent excisional biopsy. Review of the cytologic features revealed findings that should suggest angiosarcoma, especially when correlated with the clinical history. The authors describe the cytological features seen in this case, and discuss an important pitfall in the diagnosis of angiosarcoma of the breast on FNA. PMID- 7867477 TI - Is the fine-needle aspiration biopsy diagnosis of proliferative breast disease feasible? PMID- 7867478 TI - CEA content in breast lesions. PMID- 7867479 TI - Ultrasound transmission gel mimicking necrosis in ultrasound guided fine-needle aspiration specimens. PMID- 7867480 TI - [Status of immunity against poliomyelitis. Polio serosurvey in 1993]. AB - For the first time immunity against polio was analysed for the populations of both the former "East" and "West" parts of Germany, which had previously been regularly monitored separately. 10 centres for virological diagnosis collaborated. All sera were obtained between May and October 1993, a total of 3266 sera from 8 age groups. The microneutralization test was used to demonstrate antibodies against the three polio virus types. The following antibody frequencies (range in the different age groups) were found: against polio type 1, 91-93%; type 2, 93-95%; type 3, 79-81%. The seroprevalence of antibodies against polio virus types 1 and 2 of over 90% indicates good population immunity. As for virus type 3, the threshold value of 80% was exceeded in some regions. 72-75% of those tested had a neutralising antibody titre of > or = 1:4 against all three polio virus types, while in 1-2% no antibodies were found. Overall conclusion is that the relatively low state of immunity against polio virus 3 should be carefully monitored in some regions. PMID- 7867481 TI - [Complications of an idiopathic rhabdomyolysis (Meyer-Betz syndrome) after physical exertion]. AB - A few hours after a 15 km march a 19-year-old man developed a fever of 40 degrees C, accompanied by hemoptysis, tarry stools and pain in the thigh. On physical examination there was tenderness and swelling over the shoulders, upper arms and thighs as well as petechiae, bruises, hepatomegaly, pain on percussion over the kidney region and signs of hypovolaemia. There was leukocytosis (18,800/microliters) and increased creatinase activity (3900 U/l, rising to 66,300 U/l after 24 h). The platelet count fell from 147,000 to 11,000/microliters, the fibrinogen level to 0.25 milligrams. On the second day serum creatinine was 4.1 mg/dl, urine volume 50 ml/24 h, urinary myoglobin concentration 120,000 micrograms/l. The Quick value dropped to under 3%, while liver enzymes and bilirubin concentration rose. The rhabdomyolysis caused acute respiratory failure, despite symptomatic treatment of the acute renal failure and consumption coagulopathy, but after 8 weeks of intensive treatment the patient was discharged without symptoms. No cause other than the preceding physical exertion was found for the rhabdomyolysis. Muscle biopsy revealed unspecific changes 4 1/2 months after discharge. PMID- 7867482 TI - [Lovastatin-induced acute cholestatic hepatitis]. AB - Acute cholestatic hepatitis developed in two patients, a 58-year-old man and a 54 year-old woman, who had been treated for hypercholesterolaemia with the cholesterol-synthesis inhibitor lovastatin for 3 years and 2 months, respectively. Both of them at first complained only of tiredness and loss of appetite, but then developed jaundice with colourless stool and dark urine. Alkaline phosphatase concentration rose up to maximally 1227 and 569 U/l, gamma GT to 403 and 410 U/l, respectively. The transaminases and glutamate dehydrogenase were also elevated, while serum cholinesterase had fallen to 2346 and 2418 U/l, respectively. Histological examination of liver biopsies 6 months and 4 weeks, respectively, after onset of jaundice also suggested drug-toxic liver damage. There was no evidence for other causes. After lovastatin had been discontinued the various cholestasis parameters regressed only slowly. PMID- 7867483 TI - [Current diagnosis of viral hepatitis]. PMID- 7867484 TI - [Endocrine therapy of progressive breast carcinoma]. PMID- 7867485 TI - [Advertising of a corporation for ambulatory medical care. Verdict of the federal court on April 14, 1994]. PMID- 7867487 TI - [Secondary mixed cryoglobulinemia type II in chronic hepatitis C]. PMID- 7867486 TI - [Familial hypophosphatasemia]. PMID- 7867489 TI - [Nocturnal blood pressure in hypertension patients]. PMID- 7867488 TI - [Breast implants of silicone gel and the risk of connective tissue diseases]. PMID- 7867490 TI - [Helicobacter pylori infection and stomach lymphoma]. PMID- 7867491 TI - Positional signaling by hedgehog in Drosophila imaginal disc development. AB - We describe a dominant gain-of-function allele of the segment polarity gene hedgehog. This mutation causes ectopic expression of hedgehog mRNA in the anterior compartment of wing discs, leading to overgrowth of tissue in the anterior of the wing and partial duplication of distal wing structures. The posterior compartment of the wing is unaffected. Other imaginal derivatives are affected, resulting in duplications of legs and antennae and malformations of eyes. In mutant imaginal wing discs, expression of the decapentaplegic gene, which is implicated in the hedgehog signaling pathway, is also perturbed. The results suggest that hedgehog protein acts in the wing as a signal to instruct neighboring cells to adopt fates appropriate to the region of the wing just anterior to the compartmental boundary. PMID- 7867492 TI - Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny. AB - The XlHbox 8 homeodomain protein of Xenopus and STF-1, its mammalian homolog, are selectively expressed by beta cells of adult mouse pancreatic islets, where they are likely to regulate insulin expression. We sought to determine whether the expression of the homeobox protein/s during mouse embryonic development was specific to beta cells or, alternatively, whether XlHbox 8/STF-1 protein/s were initially expressed by multipotential precursors and only later became restricted to the insulin-containing cells. With two antibodies, we studied the localization of STF-1 during murine pancreatic development. In embryos, as in adults, STF-1 was expressed by most beta cells, by subsets of the other islet cell types and by mucosal epithelial cells of the duodenum. In addition, most epithelial cells of the pancreatic duct and exocrine cells of the pancreas transiently contained STF 1. We conclude that in mouse, STF-1 not only labels a domain of intestinal epithelial cells but also provides a spatial and temporal marker of endodermal commitment to a pancreatic and subsequently, to an endocrine beta cell fate. We propose a model of pancreatic cell development that suggests that exocrine and endocrine (alpha, beta, delta and PP) cells arise from a common precursor pool of STF-1+ cells and that progression towards a defined monospecific non-beta cell type is correlated with loss of STF-1 expression. PMID- 7867493 TI - Expression of the HSP 70.1 gene, a landmark of early zygotic activity in the mouse embryo, is restricted to the first burst of transcription. AB - Activation of the mouse embryonic genome at the 2-cell stage is characterized by the synthesis of several alpha-amanitin-sensitive polypeptides, some of which belong to the multigenic hsp 70 family. In the present work we show that a member of this family, the HSP 70.1 gene, is highly transcribed at the onset of zygotic genome activation. Transcription of this gene began as early as the 1-cell stage. Expression of the gene continued through the early 2-cell stage but was repressed before the completion of the second round of DNA replication. During this period we observed that the level of transcription was modulated by in vitro culture conditions. The coincidence of repression of HSP70.1 transcription with the second round of DNA replication was not found for other transcription-dependent polypeptides synthesized at the 2-cell stage. PMID- 7867494 TI - Lazarillo, a new GPI-linked surface lipocalin, is restricted to a subset of neurons in the grasshopper embryo. AB - Lazarillo, a protein recognized by the monoclonal antibody 10E6, is expressed by a subset of neurons in the developing nervous system of the grasshopper. It is a glycoprotein of 45x10(3) M(r) with internal disulfide bonds and linked to the extracellular side of the plasma membrane by a glycosylphosphatidylinositol moiety. Peptide sequences obtained from affinity purified adult protein were used to identify an embryonic cDNA clone, and in situ hybridizations confirmed that the distribution of the Lazarillo mRNA paralleled that of the monoclonal antibody labeling on embryos. Sequence analysis defines Lazarillo as a member of the lipocalin family, extracellular carriers of small hydrophobic ligands, and most related to the porphyrin- and retinol-binding lipocalins. Lazarillo is the first example of a lipocalin anchored to the plasma membrane, highly glycosylated, and restricted to a subset of developing neurons. PMID- 7867495 TI - Developmental expression of the lipocalin Lazarillo and its role in axonal pathfinding in the grasshopper embryo. AB - This article describes the expression pattern and functional analysis of Lazarillo, a novel cell surface glycoprotein expressed in the embryonic grasshopper nervous system, and a member of the lipocalin family. Lazarillo is expressed by a subset of neuroblasts, ganglion mother cells and neurons of the central nervous system, by all sensory neurons of the peripheral nervous system, and by a subset of neurons of the enteric nervous system. It is also present in a few non neuronal cells associated mainly with the excretory system. A monoclonal antibody raised against Lazarillo perturbs the extent and direction of growth of identified commissural pioneer neurons. We propose that Lazarillo is the receptor for a midline morphogen involved in the outgrowth and guidance of these neurons. PMID- 7867496 TI - Transforming growth factor alpha disrupts the normal program of cellular differentiation in the gastric mucosa of transgenic mice. AB - Transforming growth factor alpha (TGF alpha) evokes diverse responses in transgenic mouse tissues in which it is over-expressed, including the gastric mucosa, which experiences aberrant growth and a coincident repression of hydrochloric acid production. Here we show that ectopically expressed TGF alpha induces an age-dependent cellular reorganization of the transgenic stomach, in which the surface mucous cell population in the gastric pit is greatly expanded at the expense of cells in the glandular base. Immunohistochemical analysis of BrdU incorporation into DNA demonstrated that although mature surface mucous cells were not proliferating, DNA synthesis was enhanced by approximately 67% in the glandular base and isthmus, where progenitor cells reside. RNA blot and in situ hybridization were employed to determine temporal and spatial expression patterns of specific markers representing a variety of exocrine and endocrine gastric cell types. Mature parietal and chief cells were specifically depleted from the glandular mucosa, as judged by a 6- to 7-fold decrease in the expression of genes encoding H+,K(+)-ATPase, which is required for acid secretion, and pepsinogen C, respectively. The reduction of these markers coincided in time with the activation of TGF alpha transgene expression in the neonatal stomach. The rate of cell death in the glandular region was not overtly different. Significantly, the loss of parietal and chief cells occurred without a concomitant loss of their respective cellular precursors. In contrast to exocrine cells, D and G endocrine cells were much less severely affected, based on analysis of somatostatin and gastrin expression. Analysis of these dynamic changes indicates that TGF alpha can induce selective alterations in terminal differentiation and proliferation in the gastric mucosa, and suggests that TGF alpha plays an important physiological role in the normal regulation of epithelial cell renewal. PMID- 7867497 TI - Development of hematopoietic cells lacking transcription factor GATA-1. AB - GATA-1 is a zinc-finger transcription factor believed to play an important role in gene regulation during the development of erythroid cells, megakaryocytes and mast cells. Other members of the GATA family, which can bind to the same DNA sequence motif, are co-expressed in several of these hemopoietic lineages, raising the possibility of overlap in function. To examine the specific roles of GATA-1 in hematopoietic cell differentiation, we have tested the ability of embryonic stem cells, carrying a targeted mutation in the X-linked GATA-1 gene, to contribute to various blood cell types when used to produce chimeric embryos or mice. Previously, we reported that GATA-1- mutant cells failed to contribute to the mature red blood cell population, indicating a requirement for this factor at some point in the erythroid lineage (L. Pevny et al., (1991) Nature 349, 257 260). In this study, we have used in vitro colony assays to identify the stage at which mutant erythroid cells are affected, and to examine the requirement for GATA-1 in other lineages. We found that the development of erythroid progenitors in embryonic yolk sacs was unaffected by the mutation, but that the cells failed to mature beyond the proerythroblast stage, an early point in terminal differentiation. GATA-1- colonies contained phenotypically normal macrophages, neutrophils and megakaryocytes, indicating that GATA-1 is not required for the in vitro differentiation of cells in these lineages. GATA-1- megakaryocytes were abnormally abundant in chimeric fetal livers, suggesting an alteration in the kinetics of their formation or turnover. The lack of a block in terminal megakaryocyte differentiation was shown by the in vivo production of platelets expressing the ES cell-derived GPI-1C isozyme. The role of GATA-1 in mast cell differentiation was examined by the isolation of clonal mast cell cultures from chimeric fetal livers. Mutant and wild-type mast cells displayed similar growth and histochemical staining properties after culture under conditions that promote the differentiation of cells resembling mucosal or serosal mast cells. Thus, the mast and megakaryocyte lineages, in which GATA-1 and GATA-2 are co-expressed, can complete their maturation in the absence of GATA-1, while erythroid cells, in which GATA-1 is the predominant GATA factor, are blocked at a relatively early stage of maturation. PMID- 7867498 TI - Mechanisms of cell rearrangement and cell recruitment in Drosophila ovary morphogenesis and the requirement of bric a brac. AB - The Drosophila ovary consists of repeated units, the ovarioles, where oogenesis takes place. The repetitive structure of the ovary develops de novo from a mesenchymal cell mass, a process that is initiated by the formation of a two dimensional array of cell stacks, called terminal filaments, during the third larval instar. We have studied the morphogenetic process leading to the formation of terminal filaments and find that this involves recruitment, intercalation and sorting of terminal filament cells. Two other types of cell stacks that participate in ovary morphogenesis, the basal stalks and interfollicular stalks, also form by cell rearrangement utilizing a convergence and extension mechanism. Terminal filament formation depends on the Bric a brac protein, which is expressed in the nuclei of terminal filament cells and is cell autonomously required. Disruption of terminal filament formation, together with defects of basal and interfollicular stalk development, leads to disruption of ovariole formation and female sterility in bric a brac mutants. PMID- 7867499 TI - Lamina-specific cues guide outgrowth and arborization of retinal axons in the optic tectum. AB - In the chick, retinal axons enter the optic tectum through a superficial lamina, then branch into distinct deeper retinorecipient laminae, where they arborize and form synapses. To study factors that guide this laminar selectivity, we devised an organotypic culture system in which a transverse tectal section is overlaid with a retinal explant large enough to allow unimpeded access to all tectal laminae. Outgrowth, branching, and arborization patterns of retinal axons on tectal slices were lamina-selective, indicating the existence of localized cues that guide retinal axons. Further studies suggested that some of these cues are: (1) associated with cell membranes or extracellular matrix (because axons grew selectively on chemically fixed tectal sections); (2) intrinsic to the tectum (because axons grew selectively on tectal sections prepared from enucleated embryos); (3) distinct from topographic cues (because axons from nasal and temporal retina behaved similarly on anterior tectal slices); and (4) selective for retinal axons (because axons growing from other explants exhibited different laminar preferences). PMID- 7867500 TI - Transposon induced chimeras show that floricaula, a meristem identity gene, acts non-autonomously between cell layers. AB - Flower meristems comprise several distinct cell layers. To understand the role of cell interactions between and within these layers, we have generated plants chimeric for a key floral homeotic gene, floricaula (flo). These chimeras arose in Antirrhinum by excision of a transposon, restoring flo gene function. Activity of flo in a subset of cell layers gives fertile flowers with an abnormal morphology. This shows that flo can act non-autonomously between layers, although some aspects of its function are impaired. In addition, we show that flo exhibits some cell-autonomy within layers. PMID- 7867501 TI - Patterns of localization and cytoskeletal association of two vegetally localized RNAs, Vg1 and Xcat-2. AB - In Xenopus, localization of a rare class of mRNAs during oogenesis is believed to initiate pattern formation in the early embryo. We have determined the pattern of RNA localization for one of these RNAs, Xcat-2, which encodes a putative RNA binding protein related to Drosophila nanos (Mosquera, L., Forristall, C., Zhou, Y. and King, M. L. (1993) Development 117, 377-386). Xcat-2 is exclusively localized to the mitochondrial cloud in stage I oocytes, moves with this body into the vegetal cortex during stage II and, later, partitions into islands consistent with it being a component of the germ plasm. As previously shown, Vg1 is not localized to the vegetal cortex until stage IV and distributes to all vegetal blastomeres during development. We found a direct correlation between the localized condition of these RNAs and their recovery in a detergent-insoluble fraction. We present evidence suggesting that differential RNA binding to a cytoskeletal component(s) in the vegetal cortex determines the pattern of inheritance for that RNA in the embryo. PMID- 7867502 TI - DWnt-4, a novel Drosophila Wnt gene acts downstream of homeotic complex genes in the visceral mesoderm. AB - Wnt genes encode putative cell signalling proteins which play crucial roles during development. From a library of DNA fragments associated, in vivo, with Ultrabithorax proteins, we isolated a novel Drosophila Wnt gene, DWnt-4. Neither a paralog nor an ortholog of the gene exist in the current repertoire of full length Wnt sequences. DWnt-4 maps close (30 kb) to wingless, suggesting that the two Wnt genes derive from a duplication that occurred early in evolution, since they are significantly diverged in sequence and structure. Developmental expression of DWnt-4 partially overlaps that of wingless. The gene is transcribed following a segment polarity-like pattern in the posterior-most cells of each parasegment of the ectoderm, and at two locations that correspond to parasegments 4 and 8 of the visceral mesoderm. The control of DWnt-4 expression in the visceral mesoderm involves a network of regulatory molecules that includes Ultrabithorax and other proteins from the homeotic complex (HOM-C), as well as the TGF-beta decapentaplegic gene product. PMID- 7867503 TI - Neurogenic genes control gene expression at the transcriptional level in early neurogenesis and in mesectoderm specification. AB - The development of the central nervous system in the Drosophila embryo is initiated by the acquisition of neural potential by clusters of ectodermal cells, promoted by the activity of proneural genes. Proneural gene function is antagonized by neurogenic genes, resulting in the realization of the neural potential in a single cell per cluster. To analyse the relationship between proneural and neurogenic genes, we have studied, in specific proneural clusters and neuroblasts of wild-type and neurogenic mutants embryos, the expression at the RNA and protein levels of lethal of scute, the most important known proneural gene in central neurogenesis. We find that the restriction of lethal of scute expression that accompanies the restriction of the neural potential to the delaminating neuroblast is regulated at the transcriptional level by neurogenic genes. These genes, however, do not control the size of proneural clusters. Moreover, available antibodies do not provide evidence for an hypothetical posttranscriptional regulation of proneural proteins by neurogenic genes. We also find that neurogenic genes are required for the specification of the mesectoderm. This has been shown for neuralized and Notch, and could also be the case for Delta and for the Enhancer of split gene complex. Neurogenic genes would control at the transcriptional level the repression of proneural genes and the activation of single-minded in the anlage of the mesectoderm. PMID- 7867504 TI - The Drosophila orphan nuclear receptor seven-up requires the Ras pathway for its function in photoreceptor determination. AB - The Drosophila seven-up (svp) gene specifies outer photoreceptor cell fate in eye development and encodes an orphan nuclear receptor with two isoforms. Transient expression under the sevenless enhancer of either svp isoform leads to a dosage dependent transformation of cone cells into R7 photoreceptors, and at a lower frequency, R7 cells into outer photoreceptors. To investigate the cellular pathways involved, we have taken advantage of the dosage sensitivity and screened for genes that modify this svp-induced phenotype. We show that an active Ras pathway is essential for the function of both Svp isoforms. Loss-of-function mutations in components of the Ras signal transduction cascade act as dominant suppressors of the cone cell transformation, whilst loss-of-function mutations in negative regulators of Ras-activity act as dominant enhancers. Furthermore, Svp mediated transformation of cone cells to outer photoreceptors, reminiscent of its wild-type function in specifying R3/4 and R1/6 identity, requires an activated Ras pathway in the same cells, or alternatively dramatic increase in ectopic Svp protein levels. Our results indicate that svp is only fully functional in conjunction with activated Ras. Since we find that mutations in the Egf-receptor are also among the strongest suppressors of svp-mediated cone cell transformation, we propose that the Ras activity in cone cells is due to low level Egfr signaling. Several models that could account for the observed svp regulation by the Ras pathway are discussed. PMID- 7867505 TI - Control of Drosophila head segment identity by the bZIP homeotic gene cnc. AB - Mutational analysis of cap'n'collar (cnc), a bZIP transcription factor closely related to the mammalian erythroid factor NF-E2 (p45), indicates that it acts as a segment-specific selector gene controlling the identity of two cephalic segments. In the mandibular segment, cnc has a classical homeotic effect: mandibular structures are missing in cnc mutant larvae and replaced with duplicate maxillary structures. We propose that cnc functions in combination with the homeotic gene Deformed to specify mandibular development. Labral structures are also missing in cnc mutant larvae, where a distinct labral primordia is not properly maintained in the developing foregut, as observed by the failure to maintain and elaborate patterns of labral-specific segment polarity gene expression. Instead, the labral primordium fuses with the esophageal primordium to contribute to formation of the esophagus. The role of cnc in labral development is reciprocal to the role of homeotic gene forkhead, which has an identical function in the maintenance of the esophageal primordium. This role of homeotic selector genes for the segment-specific maintenance of segment polarity gene expression is a unique feature of segmentation in the preoral head region of Drosophila. PMID- 7867506 TI - Expression of floricaula in single cell layers of periclinal chimeras activates downstream homeotic genes in all layers of floral meristems. AB - We show that the flowering sectors on plants mutant for floricaula (flo), a meristem identity gene in Antirrhinum majus, are periclinal chimeras expressing flo in either the L1, L2 or L3 cell layer. Flower morphology is almost normal in L1 chimeras, but altered in L2 and L3 chimeras. Expression of flo in any one cell layer results in the expression of organ identity genes, deficiens (def) and plena (ple) in all three cell layers of the chimeras, showing that flo acts inductively to promote gene transcription. The activation of both def and ple is delayed, and the expression domain of def is reduced, accounting for some of the phenotypic properties of the chimeras. Furthermore, we show that flo exhibits some cell-autonomy with respect to autoregulation. PMID- 7867507 TI - Expression of the heparin-binding cytokines, midkine (MK) and HB-GAM (pleiotrophin) is associated with epithelial-mesenchymal interactions during fetal development and organogenesis. AB - Midkine (MK) and heparin binding-growth associated molecule (HB-GAM or pleiotrophin), constitute a new family of heparin-binding proteins implicated in the regulation of growth and differentiation (T. Muramatsu (1993) Int. J. Dev. Biol. 37, 183-188). We used affinity-purified antibodies against MK and HB-GAM to analyze their distribution during mouse embryonic development. From 9 to 14.5 day post-coitum (dpc), both proteins were detected in central and peripheral nervous systems, facial processes, limb buds, sense organs, respiratory, digestive, urogenital, and skeletal systems. MK and HB-GAM were often localized on the surface of differentiating cells and in basement membranes of organs undergoing epithelial-mesenchymal interactions. The level of MK protein decreased considerably in the 16.5 dpc embryo, whereas HB-GAM staining persisted in many tissues. Our in situ hybridization results revealed a widespread expression of MK transcripts that was not always consistent with the distribution of MK protein in developing tissues. In many epithelio-mesenchymal organs MK and HB-GAM were codistributed with syndecan-1, a cell surface proteoglycan. In limb buds and facial processes, MK, HB-GAM, and syndecan-1 were localized to the apical epithelium and the adjacent proliferating mesenchyme. Both MK and HB-GAM bound syndecan-1 in solid-phase assays in a heparan sulfate-dependent manner. The biological effects of MK and HB-GAM on limb and facial mesenchyme were studied in vitro by application of beads preloaded with the proteins. Neither MK nor HB-GAM stimulated mesenchymal cell proliferation or induced syndecan-1 expression. Taken together these results indicate that MK and HB-GAM may play regulatory roles in differentiation and morphogenesis of the vertebrate embryo, particularly in epithelio-mesenchymal organs, and suggest molecular interactions with syndecan-1. PMID- 7867508 TI - Mitotic delay dependent survival identifies components of cell cycle control in the Drosophila blastoderm. AB - The Drosophila body pattern is laid down by maternal and zygotic factors which act during the early phase of embryonic development. During this period, nascent zygotic transcripts longer than about 6 kilobases are aborted between the rapid mitotic cycles. Resurrector1 (Res1) and Godzilla1 (God1), two newly identified dominant zygotic suppressor mutations, and a heterozygous maternal deficiency of the cyclin B locus, complement the partial loss of function of the segmentation gene knirps (kni) by extending the length of mitotic cycles at blastoderm. The mitotic delay caused by Res1 and God1 zygotically and by the deficiency of the cyclin B locus maternally allows the expression of a much longer transcript of a kni cognate gene normally aborted between the short mitotic cycles and consequently allows survival of kni mutant progeny. In addition to the practical benefits of identifying mutations in Drosophila cell cycle regulatory genes as suppressors of kni, our results have evolutionary implications regarding the flexibility of the genome to meet sudden selective pressures by recruiting cognate genes to function. PMID- 7867509 TI - Axogenesis in the embryonic brain of the grasshopper Schistocerca gregaria: an identified cell analysis of early brain development. AB - Axogenesis in the embryonic brain was studied at the single cell level in the grasshopper Schistocerca gregaria. A small set of individually identifiable pioneer neurons establishes a primary axon scaffold during early embryogenesis. At the beginning of scaffold formation, pioneering axons navigate along and between glial borders that surround clusters of proliferating neuroblasts. In each brain hemisphere, an axonal outgrowth cascade involving a series of pioneer neurons establishes a pathway from the optic ganglia to the brain midline. At the midline the primary preoral commissural interconnection in the embryonic brain is pioneered by a pair of midline-derived pioneer neurons. A second preoral commissural connection is pioneered by two pairs of pars intercerebralis pioneer neurons. Descending tracts are pioneered by the progeny of identified neuroblasts in the pars intercerebralis, deutocerebrum and tritocerebrum; the postoral tritocerebral commissure is pioneered by a pair of tritocerebral neurons. All of the pioneering brain neurons express the cell adhesion molecule fasciclin I during initial axon outgrowth and fasciculation. Once established, the primary axon scaffold of the brain is used for fasciculation by subsequently differentiating neurons and, by the 40% stage of embryogenesis, axonal projections that characterize the mature brain become evident. The single cell analysis of grasshopper brain development presented here sets the stage for manipulative cell biological experiments and provides the basis for comparative molecular genetic studies of embryonic brain development in Drosophila. PMID- 7867510 TI - Neuroectodermal fate of epiblast cells in the distal region of the mouse egg cylinder: implication for body plan organization during early embryogenesis. AB - The developmental fate of cells in the distal region (distal cap) of the epiblast was analysed by fate mapping studies. The displacement and differentiation of cells labelled in situ with carbocyanine dyes and lacZ-expressing cells grafted to the distal cap were studied over a 48-hour period of in vitro development. The distal cap epiblast differentiates predominantly into neurectodermal cells. Cells at the anterior site of the distal cap colonise the fore-, mid- and hindbrain and contribute to non-neural ectoderm cells of the amnion and craniofacial surface ectoderm. Those cells in the most distal region of the epiblast contribute to all three brain compartments as well as the spinal cord and the posterior neuropore. Cells at the posterior site of the distal cap are mainly localised to the caudal parts of the neural tube. A minor contribution to the embryonic (paraxial and lateral) and extraembryonic (allantoic and yolk sac) mesoderm is also found. Epiblast cells located outside the distal cap give rise to surface ectoderm and other non-ectodermal derivatives, with only a minor contribution to the neuroectoderm. Results of this study provide compelling evidence that the precursor population of the neural tube is contained in the distal cap epiblast of the early-primitive-streak-stage embryo. Furthermore, the regionalisation of cell fate within this small population suggest that a preliminary craniocaudal patterning may have occurred in the neural primordium before neurulation. PMID- 7867511 TI - The dual role of hermaphrodite in the Drosophila sex determination regulatory hierarchy. AB - The hermaphrodite (her) locus has both maternal and zygotic functions required for normal female development in Drosophila. Maternal her function is needed for the viability of female offspring, while zygotic her function is needed for female sexual differentiation. Here we focus on understanding how her fits into the sex determination regulatory hierarchy. Maternal her function is needed early in the hierarchy: genetic interactions of her with the sisterless genes (sis-a and sis-b), with function-specific Sex-lethal (Sxl) alleles and with the constitutive allele SxlM#1 suggest that maternal her function is needed for Sxl initiation. When mothers are defective for her function, their daughters fail to activate a reporter gene for the Sxl early promoter and are deficient in Sxl protein expression. Dosage compensation is misregulated in the moribund daughters: some salivary gland cells show binding of the maleless (mle) dosage compensation regulatory protein to the X chromosome, a binding pattern normally seen only in males. Thus maternal her function is needed early in the hierarchy as a positive regulator of Sxl, and the maternal effects of her on female viability probably reflect Sxl's role in regulating dosage compensation. In contrast to her's maternal function, her's zygotic function in sex determination acts at the end of the hierarchy. This zygotic effect is not rescued by constitutive Sxl expression, nor by constitutive transformer (tra) expression. Moreover, the expression of doublesex (dsx) transcripts appears normal in her mutant females. We conclude that the maternal and zygotic functions of her are needed at two distinctly different levels of the sex determination regulatory hierarchy. PMID- 7867512 TI - Thyroid hormones and the central nervous system. AB - Thyroid hormones have a significant influence on the development and maturation of the central nervous system. Among their actions, T3 and T4 have effects on the differentiation of various cell types in the rat brain and cerebellum as well as on the process of myelination. Recently, several investigators have shown effects of thyroid hormones on myelin protein gene expression. Thyroid hormones seem to have a regulatory role with regard to life span. Hyperthyroid animals appear to have a shorter life and, at advanced age, show a myelin deficit. This may be due to the damage produced by the oxidative stress generated by an excess of thyroid hormones. PMID- 7867513 TI - Both afferent and efferent connections influence postnatal growth of motoneuron dendrites in the rat. AB - Spinal motoneurons from mature rats, which had received one of 5 different surgical procedures neonatally, were retrogradely labelled with a cholera toxin horseradish peroxidase conjugate and their dendritic morphology was analysed. The motoneurons studied were those innervating extensor digitorum longus and the procedures disrupted their motor and sensory connections to varying degrees. Disruption of motor contact with the target muscle retarded dendritic growth in the transverse plane, particularly in the dorso-medial direction. Disruption of sensory as well as motor contact resulted additionally in an increase in dendritic density in the longitudinal plane, largely along the rostral-caudal axis. The findings suggest that dendritic development of motoneurons is influenced by both afferent and efferent target contacts and that these effects can be differentiated. PMID- 7867514 TI - Immature maxi-K channels exhibit heterogeneous properties in the embryonic rat telencephalon. AB - Using the cell-attached configuration of the patch-clamp technique, we recorded large-conductance K channels (LCKs) from intact telencephala and cortical slices of embryonic (E) 12-14 and E21 rats, respectively. Conductance (about 200 pS with K(+)-rich pipettes), kinetics and sensitivity to fatty acids (FAs) were reminiscent of some features of the Ca-activated 'maxi-K' channel (BK), yet less than half the LCKs were Ca-sensitive. At E12-14, an even smaller proportion of the channels were strictly voltage-sensitive, that proportion rising to about 50% at E21. Ca and voltage sensitivities were observed independent of one another. The open probability of voltage-sensitive LCKs increased exponentially with depolarization rates similar to those reported for classical BKs. It is postulated that embryonic LCKs may constitute immature forms of BKs whose gating is regulated by endogenous FAs. PMID- 7867515 TI - Developmentally regulated in vitro phosphorylation of cytoskeletal proteins of the cerebral cortex of normal and malnourished rats. AB - In this investigation we studied developmentally regulated endogenous protein kinase activity in cytoskeletal proteins in the cerebral cortex of rats and the effect of early malnutrition imposed on dams on the pattern of 32P incorporation into the cytoskeleton of pups. Our results indicated that in vitro incorporation was maximum in 7-day-old pups for both normal and malnourished groups, decreasing with development, and reaching minimum values in adult animals. However, 32P incorporation into NF-M and tubulin was significantly lower in 7-day-old malnourished pups than in normal pups. PMID- 7867516 TI - Developing substantia nigra in human: a qualitative study. AB - Midbrains from 43 fresh human embryos and fetuses at 8-22 weeks of gestation were processed for routine histology, Golgi staining, tyrosine hydroxylase (TH) immunolabelling and retrograde tracing with the fluorescent dye DiI. Cells were immature and densely packed between 8 and 10 weeks. By 13 weeks cells could be identified as neurons and glia. Neurons matured gradually and achieved adult characteristics by 20-22 weeks. Neurons in the paramedian regions of the tegmentum, raphae region and substantia nigra were positive for TH from 13 weeks onwards, the earliest age group used for this technique. The presence of TH positive neurons in the paramedian part of the tegmentum until 18 weeks and radial glial fibers extending from the aqueductal lining to the ventral part until 20 weeks were suggestive of migration of neurons to the ventral mesencephalon region. DiI labelling of the neurons and fibers of ipsilateral nigra from the caudate as early as 10 weeks demonstrated early nigrostriatal connections. The mature nature of the neurons appeared only by 13 weeks by this method. The present study shows that the nigral neurons in the human migrate and mature until mid-gestation. The nigrostriatal connection at 10 weeks suggests a trophic influence of nigra on the proliferating and maturing neurons of the striatum. PMID- 7867518 TI - Developmental characteristics of the chick nodose ganglion. AB - Morphometric studies were carried out on the chick nodose ganglion between day 5 of incubation and 2 weeks after hatching. Previous findings showed that ablation of the nodose placode, the locus of precursor cells of nodose ganglion sensory neurons, results in abnormal cardiac function, and that these precursors can be induced to migrate abnormally to the heart and express abnormal phenotypes there, following cardiac neural crest ablation. These results prompted us to investigate further the normal development of nodose ganglion neurons. We find that the major period of neuron generation from placodal precursor cells in the ganglion occurs prior to day 5 of incubation. The loss of more than half of these neurons takes place between embryonic days 5 and 20, while neuron and ganglion sizes increase dramatically. Myelination is not seen at day 12 of incubation, but is present on day 15. Neurons continue to develop after hatching (day 21), reaching their adult size by 2 weeks after hatching. Unexpectedly, we found that the number of neurons increases after hatching, reaching the adult level of 62% more than embryonic day 20 numbers by 2 weeks after hatching. The mechanisms underlying the increase in neuron number after hatching are unexplained and require further investigation. PMID- 7867517 TI - Expression of the neuron-specific FE65 gene marks the development of embryo ganglionic derivatives. AB - The major transcript of the FE65 gene is a neuron-specific mRNA that encodes a nuclear protein whose aminoterminal domain strongly activates the transcription of a reporter gene when fused to a heterologous DNA-binding domain. FE65 gene expression is regulated during neuronal differentiation of the NTERA-2 cell line, and it is temporally and spatially restricted during mouse embryo development. It is first detected around day 10 of gestation in the basal plate of the neural tube, and then, at the subsequent stages of development and in the newborn animals, it is found solely in neural structures. Its expression is most abundant in the neural crest derivatives (e.g. spinal and encephalic ganglia), ganglionic structures of sense organs (ganglionic layer of the retina and olfactory epithelium), as well as the ganglionic structures of the autonomic nervous system. Thus FE65 gene expression can be considered a marker of the development of embryo ganglionic derivatives. PMID- 7867519 TI - Noradrenergic innervation of ectopic granule cells following low-level X irradiation. AB - The distribution pattern of the noradrenergic system within the cerebellar cortex following low-level X-irradiation was studied using immunocytochemistry. Following one X-irradiation exposure on postnatal day 1, the laminar distribution of tyrosine hydroxylase-like immunoreactive (THIR) fibers was similar to controls at postnatal day 30, but the orientation of the fibers in the molecular layer (ML) was slightly changed. Successive daily doses, however, produced alterations in both the pattern and concentration of THIR fibers within the ML of the cerebellar cortex. In addition, THIR fibers were found among ectopic cell clusters within the ML. This relationship suggests a potential role for the noradrenergic system in the development and/or maintenance of the ectopic cell clusters. PMID- 7867520 TI - Noradrenergic innervation of the external granular layer of the rat following low level X-irradiation. AB - The distribution of the noradrenergic system within the rat cerebellar cortex following low-level X-irradiation was studied using tyrosine hydroxylase immunocytochemistry. X-Irradiation treatments consisted of 1, 3, or 5 successive daily dose beginning on postnatal day 1. When studied 24 h after the last exposure, a dense plexus of tyrosine hydroxylase-like immunoreactive (THIR) fibers, not found in age-matched controls, was observed in the reduced external granular layer (EGL) in each treatment group. At 10 days of age, the THIR fibers were found in association with the reconstituted cells of the premigratory zone of the EGL. The rapid and abnormal innervation of the EGL by the THIR fibers suggests that the noradrenergic system could play a role in the regeneration of this layer. PMID- 7867521 TI - Cerebral implants of histotypic hypothalamic cultures. AB - In the present report, the implantation of hypothalamic histotypic cultures within the cerebral hemisphere is described. The cultures were prepared from 10 day-old mice and rotary incubated during 6 or 10 days. When the cells reached their phenotypic characteristics at the end of the incubation period, the cultures were implanted in the posterior area of the lateral ventricle. 30 days postoperatively, the whole implanted area was removed and processed for light and electron microscopy observations. The implanted cultures completed maturation in the host tissue and no rejection signs were noticed; on the contrary, we were able to observe a favorable reaction from the host tissue, such as the formation of secondary blood vessels which penetrated the mass of the implanted culture. Well-developed magno- and parvocellular neurons were seen to contain neurosecretory vesicles in their terminals, and the neuroglial relationships established within these implants were homologable to those normally found. PMID- 7867522 TI - Expression of sphingolipid activator protein gene in brain and systemic organs of developing mice. AB - The sphingolipid activator proteins (SAPs) are a family of small, heat-stable glycoproteins, proven or postulated to be required for in vivo degradation of some sphingolipids by hydrolytic enzymes. Four of them are coded by a single gene, which generates a transcript including the four saps in tandem. The large translation product is then proteolytically cleaved to generate individual saps. A hypothesis has been advanced that the large sap-precursor protein might by itself have functions distinct from the processed individual saps. Expression of the gene in the brain regions and other organs of 9-, 20- and 60-day-old mice was examined by Northern blot analysis. It was expressed in all tissues and organs examined. However, the expression level was higher in the nervous system than in systemic organs. The level of sap expression remained constant in several regions of the nervous system, and in the systemic organs decreased from 9 to 60 days, particularly in the heart and kidney. In situ hybridization analysis indicated that while the transcript was found throughout the adult mouse brain, the epithelial cells of the choroid plexus showed the highest expression level, followed by various gray matter areas, including cortex and hippocampus. Generally, the mRNA was associated with neuronal perikarya rather than neuropiles or glial cells. This regional distribution was similar at the ages examined. PMID- 7867523 TI - Vocal fold hemorrhagic mass: functional implications. PMID- 7867524 TI - Temporal bone fracture conductive hearing loss. PMID- 7867526 TI - The how and why of facelift incisions. PMID- 7867525 TI - Preparation of antigens for the diagnosis and treatment of allergy. Part 1: Raw materials. PMID- 7867527 TI - Acoustic neuroma surgery in patients over 65 years of age. AB - Patients over 65 years old develop acoustic neuromas with the same signs and symptoms as younger patients. Age limits beyond which surgery for acoustic neuroma is not offered have been suggested. Untreated vertigo in the older patient frequently results in a fall which causes a fracture of the femur followed by significant morbidity and mortality. A review of 62 cases done over a period of five years reveals that surgical removal of acoustic neuroma in eight patients over 65 years of age gave results equally good to those in younger patients. This study suggests that the patient's general medical condition, life expectancy and factors other than chronologic age should be considered in the indications for surgery of acoustic neuroma. Acoustic neuroma surgery for the older patient can provide gratifying results. PMID- 7867528 TI - Early oral feeding after total laryngectomy. AB - Following total laryngectomy, 110 patients were orally fed on the first/second postoperative day without using a nasogastric (NG) tube. Pharyngo-cutaneous fistula was observed in 23 patients (21%) only nine of which (8%) needed surgical intervention to close the fistula. Early postoperative oral feeding of laryngectomized patients does not increase the fistula rate but decreases postoperative hospitalization time and eliminates the disadvantages of the NG tube. PMID- 7867529 TI - When is isolated vertigo a harbinger of stroke? AB - Isolated vertigo is usually a distressing though benign clinical entity. Recently, however, it has been recognized that in a subset of patients isolated vertigo may be a harbinger of vertebrobasilar stroke. Recognition of this "at risk" subgroup may be difficult. Brainstem auditory evoked potentials (BAEPs) are usually normal in patients with vertigo from labyrinthine disease. We describe a patient with isolated vertigo, in whom BAEPs were abnormal, and who subsequently developed an anterior inferior cerebellar artery territory infarct. BAEP testing might lead to early recognition of those patients at risk for catastrophic stroke, and prompt appropriate investigation and treatment to prevent this outcome. PMID- 7867531 TI - Differentiating bony lesions of the external auditory canal. PMID- 7867530 TI - Dysphagia in patients with three different etiologies of salivary gland dysfunction. AB - Dysphagia is a common complaint from patients with salivary gland dysfunction (SGD). The purpose of this study was to assess and compare dysphagia in three patient groups with SGD: primary Sjogren's syndrome (SS-1); secondary Sjogren's syndrome with systemic lupus erythematosus (SS-2-SLE) and a group of patients who had post-irradiation therapy (PIT) (for head and neck cancer xerostomia) and a matched control group. Subjects diagnosed with SS-1 (n = 7); SS-2-SLE (n = 7) and PIT (n = 7) were selected for the study. An age-sex-matched group of control subjects (n = 7) was selected for comparison. Dysphagia assessments, including videofluoroscopy, were performed. Subjective evaluations were recorded on a calibrated 10-cm visual analog scale. The results indicated a significant difference in the DS as compared to the WBS for all SGD groups and for both DS and WBS in each SGD group as compared to controls. Videofluoroscopy also yielded significantly prolonged pharyngeal transit times (PTT) in all SGD groups as compared to controls. Subjective results indicated a greater degree of dysphagia symptoms in all of the SGD groups (p < 0.001). Conclusions from this study indicate clinically significant dysphagia in patients with SS-1, SS-2-SLE and PIT as compared to a control population. PMID- 7867532 TI - Parapharyngeal space lipoma. PMID- 7867533 TI - Retropharyngeal abscess after adenoidectomy. AB - In this paper, we describe a case of retropharyneal abscess with atlantoaxial joint subluxation after an adenoidectomy. This is a rare complication of which the otolaryngologist must be aware because of its potential consequences. PMID- 7867534 TI - Endoscopic view of a foreign body in the nose. PMID- 7867535 TI - AIDS research: are we in the right direction? PMID- 7867536 TI - Demographic and AIDS-related characteristics of consenters to a population-based HIV-survey: results from a pilot study in Arusha, Tanzania. AB - The aim was to compare demographic and AIDS-related characteristics of people who consented to HIV-testing as part of a population survey with those who did not consent to HIV-testing. Subjects, aged 15-54 years, living in ten randomly selected clusters of households in one ward of Arusha town were asked to participate in a structured interview and to provide a blood sample for HIV testing. Measurements included demographic variables and AIDS-related factors, such as knowledge of AIDS and sexual behaviour, and HIV-testing with Western Blot confirmation. Sixty-two percent of the eligible population (N = 600) participated in the interview, while 38% consented to HIV-testing. Odds ratio analysis techniques were used to compare consenters and non-consenters. More women than men participated in the interview (OR = 4.23), and participating men were younger than non-participating men (29.1 vs 31.9 years). Subjects who had attended secondary school were underrepresented among the HIV- test consenters (OR = 0.40). No other demographic or AIDS-related differences were observed between HIV test consenters and non-consenters. At least in this pilot, non- consenters did not appear to be at any higher risk for HIV-infection than the consenters. Future population-based HIV-surveys might have to compromise on maximizing participation rate in order to secure informed, non-coerced consent from participants. PMID- 7867537 TI - Human immunodeficiency virus- 1 in leprosy patients attending Kenyatta National Hospital, Nairobi. AB - The purpose of this study was to determine if Mycobacterium leprae is an opportunistic pathogen in immunosuppressed subjects with HIV infection. Ninety six leprosy patients at Infectious Diseases Hospital (IDH), Nairobi were screened for, HIV-1 antibody between January 1991 and June 1992. The patients included 15 who were diagnosed during the study period and 81 who were previously diagnosed and were on anti-leprosy treatment. Blood was screened for HIV antibody by first ELISA and double positive samples were confirmed by a second ELISA. The HIV seronegative patients were re-tested serologically every 3 months. Smears from skin slits were used to determine bacterial index and the patients were classified according to criteria described by Ridley and Jopling. The patients were re-assessed clinically monthly. The mean age of the patients was 40 years and ranged from 13 to 78 years. Forty seven percent had paucibacillary and 53% had multibacillary leprosy. The HIV seroprevalence was 8% in previously diagnosed patients and zero in the newly diagnosed patients. There were no changes in clinical spectrum in HIV seropositive patients during follow up period; neither reversal reactions nor erythema nodosum leprosum were observed. The study suggests that M. leprae may not be an opportunistic pathogen in immunosuppressed subjects with HIV infection. PMID- 7867538 TI - Therapeutic effect of an anti-HIV candidate vaccine. AB - A chimpanzee infected with the HIV since 8 months and presenting regularly with antigenemia was inoculated with a candidate vaccine. It received 3 doses, one dose every 15 days. Thirty days after the third injection, we noted the disappearance of the HIV antigens in the serum and its persistence in the lysate of the cells. We noted also a strong precipitation reaction both in the tube and in the gel between the antibodies and the antigens released by the lysis of the cells. The analysis of this precipitate demonstrated that it was constituted of immune complexes in which the antibodies were of high affinity. At the 240th day after the third injection of the candidate vaccine we noted the disappearance of the HIV antigens in the lysate of cells as well. From these results, we conclude that the candidate vaccine we tested can elicit high affinity antibodies able to clear the HIV antigens and destroy the cells containing the HIV antigens probably with the help of specific killer cells. PMID- 7867539 TI - Endoscopic study of African AIDS patients with upper gastrointestinal symptoms. AB - This study was carried out to investigate the endoscopic and histopathological findings in AIDS patients in Mulago Hospital, in Uganda who present with upper gastrointestinal symptoms. Any observed morphological changes were biopsied. Duodenal contents were aspirated in each case for microscopic examination. Vomiting was reported in 100% of the patients, dysphagia and epigastric pain were reported in 89%. Other symptoms reported in decreasing frequency were odynophagia 46%, retrosternal chest pain 40%, haematemesis 10%, and hiccough 3%. Up to 74% of the patients had morphological changes in the oesophagus, while 28% showed changes in the stomach. Only 15% demonstrated changes in the duodenum. Duodenal aspirate revealed giardia lamblia 22%, Acid fast bacilli 7% and cryptosporidium 5%. Endoscopic findings were mostly observed in the oesophagus. Candida was the main pathogen detected. Also atrophic gastritis is a recognizable finding in these patients. PMID- 7867540 TI - Highly resistant bacterial osteomyelitis in Somalia. AB - Chronic osteomyelitis is a major health problem in the aftermath of the conflict in Somalia. We studied the microbiology of chronic osteomyelitis among 30 patients in a large hospital in Mogadishu. Gram-negative bacteria were isolated from 77% of patients; most of these isolates were highly resistant to standard antibiotic agents but all were sensitive to ciprofloxacin, an oral fluoroquinolone antibiotic. Ciprofloxacin may prove useful in the management of chronic osteomyelitis due to highly resistant gram-negative bacteria. PMID- 7867541 TI - Echogenicity of the foetal telencephalic choroid plexus as a developmental landmark: a preliminary report. AB - Echogenicity of the telencephalic choroid plexus was observed in 34% of foetuses examined consecutively in routine obstetrical sonograms. Foetuses with echogenic were all aged between 13 and 23 weeks. 70% of the foetuses showing the echogenic plexus were in the second trimester. 80% of these foetuses were scanned during the fifth month of pregnancy (aged between 15 and 19 weeks). The biparietal diameter of 87% of the skulls with echogenic plexus ranged between 22 and 50mm. The characteristic appearance of the normal plexus during a certain period in the second trimester confirms its transient nature and suggests an underlying developmental mechanism. It appears and disappears well before the disease entities presenting in similar cephalic echogenicities. PMID- 7867542 TI - Childhood accidents in an urban community in Kenya. AB - A retrospective study was conducted over a twenty-month period from March 1991 to October 1992. The purpose of the study was to determine the types and causes of domestic accidents/injuries in the city of Nairobi. A total of 9,648 case files were perused and out of this figure 52% or 5009 records belonged to persons aged below 18 years. The male:female ratio was 1.6:1. Burns were identified as the most prevalent type of injury (37%) followed by cuts/wounds (24.9%) and body swellings (4.9%). The main causes of these accidents were: fire, falls inside and outside the house and cutting implements. These results are only an index to a problem that has been given little prominence in the field of public health. PMID- 7867544 TI - Survival and growth of selected pathogens in fermented kocho (Ensete ventricosum). AB - A study was conducted to investigate the antagonistic potential of fermented kocho, aqueous extract of fermented kocho and spent media from lactic acid bacteria (LAB) isolated from it on Salmonella sp, Pseudomonas aeruginosa, Klebsiella sp, Bacillus cereus and Staphylococcus aureus. Fermented kocho (pH 4.3) inhibited growth of the test bacteria soon after their introduction into the food. The spent media from all of the four LAB, isolated from fermented kocho, namely Pediococcus sp, Leuconostoc sp, Lactobacillus sp and Streptococcus sp prevented the survival and growth of the test bacteria. The spent medium from Streptococcus sp showed the best antagonistic effect amongst all the LAB isolates. In all cases the inhibitory effects were independent of pH. PMID- 7867543 TI - Giant goitre: a surgical scourge. AB - The giant goitre is an interesting phenomenon almost exclusively confined to regions of endemic goitre. A majority of patients with giant goitre usually desire operation for social and cosmetic reasons. Some of them however suffer frequent attacks of intercurrent respiratory tract infection which complicates the post-operative course. About a fifth of them present with acute respiratory distress requiring emergency surgery. The peri-operative management of this disease is both formidable and hazardous. The operative time is not only longer than for a standard thyroidectomy but mortality can also be unacceptably high. In this paper the author reports his personal experience with 30 patients whose resected specimens weighed between 500g and 1750g. There was a total of six complications; one patient developed a deep haematoma which produced respiratory distress post-operatively. Five patients developed suture abscesses at intervals after the operation. There was no mortality. PMID- 7867545 TI - Postnatal growth of abandoned preterm babies. AB - Eighteen abandoned low birth weight infants matched for sex and gestational age with infants who had mothers were followed up till discharge or death. Anthropometric measurements were taken on recruitment and then weekly. Initially all infants were on breast milk. For the abandoned ones, milk was obtained from other mothers. Results show that the abandoned infants were on breast milk until they attained a mean weight of 1960gm. This coincided with a postnatal age of 6 weeks. For the rest of the period they were on artificial feed. Mean birth weight was 1403 +/- 302 and 1337 +/- 204 for cases and controls respectively while the mean gestation was 30 weeks. Anthropometric measurements were similar at the beginning of the study and both groups regained birth weight at 2 weeks. Thereafter the rate of weight gain of 16gm per day for the cases was significantly lower than that of 22gm per day for the controls. Similarly midarm circumference increases were much lower in the cases than in controls (0.2cm versus 0.4 per week). There were however no significant differences in length and head circumference increases. A significant number of cases (94.4%) had one or more episodes of serious infection and 38.9% died. None of the control infants died and only 10.5% had serious infection. PMID- 7867546 TI - Treatment of thyroid cancer. AB - The management of differentiated thyroid cancer remains controversial. A consecutive series of 234 thyroidectomies done by one surgeon in various Nairobi Hospitals from July 1990 to June 1993 were studied. 18 patients were operated on for thyroid cancer. The procedures ranged from lobectomy to total thyroidectomy. Young adults from 20-40 years of age were mainly affected, with a male/female sex ratio of 8:1. The immediate and subsequent morbidity of the operation of total thyroidectomy, in our opinion, overweighs its advantages of improved disease control. This is particularly so when low socio-economic standards lead to lack of compliance with replacement therapy. PMID- 7867547 TI - An aetiological survey of paraplegia in Accra. AB - Sixty-four cases of non-traumatic paraplegia in Accra, Ghana, were investigated. The commonest cause of paraplegia was tuberculosis (29.69%). Next were transverse myelitis and the Guillain-Barre syndrome, each accounting for 10.94% of cases. Parasitic causes were not seen in this study. The other important causes are neoplastic conditions (14.07%) and degenerative conditions namely, cervical spondylosis with myelopathy (12.5%), and motor neurone disease (6.25%). It is concluded that the major causes of non-traumatic paraplegia in Accra are related to non-parasitic microbial infections (51.57%). PMID- 7867548 TI - Management of diarrhoea at the household level: a population-based survey in Suleja, Nigeria. AB - Home management of diarrhoea was studied in 1,638 children under 5 years of age whose 1,160 mothers we randomly selected in Suleja local government area (LGA) in November 1991. The sampling method used was a cluster scheme based on "probability proportionate to size", with 40 clusters randomly selected. Prevalence of diarrhoea during the two preceding weeks was 20.8%; 73.8% of the cases were in children under two years of age; 32% of the children had received no treatment, and 56% of the mothers had used health facilities (Government and private). The estimated annual incidence rate of diarrhoea disease was 4.6 episodes per child. During episodes of diarrhoea, almost all mothers continued breast-feeding and giving other available home fluids, but 42.2% stopped solid food. Forty-four percent of mothers gave sugar-salt-solution (SSS) at home for diarrhoea; nearly half (45.3%) of them could not prepare the solution correctly. Mothers treated at home with SSS, herbs and fluids significantly more often when the diarrhoea was perceived as severe. Mothers sought help outside the home (at a health facility or traditional healer) significantly more often for severe cases. The survey provides important information about what happens at home - the place where diarrhoeal disease control programmes succeed or fail. The findings highlight the communication messages that need to be devised for mothers. Since government health facilities remains the commonest (87%) source of information on diarrhoea, health workers need to be equipped with the skills for advising mothers on management of diarrhoea in the home. PMID- 7867549 TI - Clinical aspects and causes of rickets in a Kenyan population. AB - Twenty nine patients with rickets were studied in a one year period. The majority of patients (17/29) were below 2 years of age. Most of them had nutritional rickets resulting from a combination of factors. Premature delivery, nonexposure to sunlight, nutritional marasmus and inappropriate dietary intake. Some had familial hypophosphataemic rickets, others had renal tubular acidosis while the rest had rickets with a familial tendency. Both the previous hospital records and the present study indicate that rickets is a persistent problem in children in the community and should be suspected in children who present with features of failure to thrive, among other conditions. PMID- 7867550 TI - Idiopathic pulmonary calcinosis: a variant of alveolar microlithiasis. AB - Diffuse pulmonary calcinosis has been observed in hyperparathyroidism, chronic renal disease, vitamin D intoxication, but has never been reported in the absence of any underlying disease. We report the case of a young man in whom diffuse pulmonary calcifications was found without any underlying disease and whose clinical and histological features suggest a variant or an incomplete form ('forme fruste') of alveolar microlithiasis. PMID- 7867551 TI - Variability of egg excretion in Schistosoma mansoni infection in Ethiopia: a case report. AB - An Ethiopian boy, aged 18 years, and heavily infected with S. mansoni (1250 eggs per gram of faeces), gave stool sample for microscopy three times a day (at 9:00 am, 1:00 pm and 4:00 pm) for 5 consecutive days. Each time two slides were prepared by the modified Kato's thick-smear technique. The maximum egg count at each examination was converted to eggs per gram of faeces (EPG). There was no significant variability (at 10% level, F-value = 0.04) in in egg counts made at different times of the day. However, the coefficient of variations between the egg counts made on different days were fairly high ranging from nearly 61% to 73% and the differences being highly significant at 10% level (F value = 4.076). The implications of this day-to-day variability of S. mansoni faecal excretion in "selected" chemotherapy in Ethiopia is discussed. PMID- 7867552 TI - Inhaled salmeterol. PMID- 7867553 TI - Aberrant temporal patterning of slow-wave sleep in siblings of SIDS victims. AB - We assessed the patterning of slow-wave EEG activity during sleep in siblings of sudden infant death syndrome (SIDS) victims over the first 6 months of life. Twelve hour overnight physiologic recordings were obtained from 25 apparently healthy subsequent siblings of SIDS victims and 25 control infants at 1 week, and 1, 2, 3, 4 and 6 months of age. The EEG activity was electronically bandpass filtered, leaving primarily activity ranging from 0.5 to 2.5 Hz (the delta frequency), and the filtered traces were full-wave rectified and integrated over 1 min periods. The recordings were divided into four 3 h segments beginning at sleep onset, and the mean integrated delta activity during quiet sleep was determined for each segment of the night. At 3 and 4 months postnatal age, SIDS siblings displayed increased integrated delta amplitude in the early morning hours relative to control infants. Most SIDS deaths occur in the early morning hours during the 2-4 month age range. We thus speculate that increased delta activity may be indicative of increased arousal thresholds in the early morning, which may contribute to SIDS deaths. PMID- 7867554 TI - Delineation of thyroid hormone-responsive sequences within a critical enhancer in the rat uncoupling protein gene. AB - Uncoupling protein (UCP) is essential to brown adipose tissue (BAT) thermogenesis and, hence, to cold adaptation and energy balance. The sympathetic nervous system, via norepinephrine and cAMP, and thyroid hormone seem to be the major regulators of UCP expression. T3 potentiates the effect of norepinephrine and is essential for the adaptive response of this protein to cold. The goal of the present studies was to investigate whether T3 directly stimulates the transcription of the rat UCP gene, as suggested by in vivo results, and if so, to identify and characterize the sequences involved. We examined the gene sequence between 114 and -3623 by transient transfection analysis in JEG-3 and HIB-1B cells, a BAT-derived cell line. This 3.7-kilobase UCP insert makes the reporter gene responsive to cAMP (4-fold), T3 (4-fold), or both combined (12-fold). We identified an 82-basepair (bp) restriction fragment between -2317 and -2399, which we called thyroid hormone response sequence (THRS), that conferred T3 responsiveness to the UCP minimal promoter (4- to 12-fold) as well as to the thymidine kinase promoter (3- to 6-fold). T3 receptor bound to THRS in vitro, retarding its migration in electrophoretic mobility shift assays. Footprinting of THRS revealed two potential thyroid hormone response elements (TRE) separated by 27 bp: upTRE, -2391/-2376, 5'ACCCCTACTGAGGCAA; and dnTRE, -2348/-2334, 5'AGGGCAGCAAGGTCA. The mutation of these putative TREs caused loss of both T3 receptor binding and transactivation by T3. The analysis of the mutants also demonstrated that both TREs contribute in similar proportion to the T3 responsiveness of the UCP gene and that dnTRE is necessary for the potentiation of the cAMP effect by T3. Both TREs are located within a previously identified 212-bp enhancer element, flanked by sequences considered essential for BAT expression and norepinephrine responsiveness. Although they do not mediate thyroid hormone responsiveness, the sequences flanking THRS increase basal reporter expression and enhance the responses to T3. In conclusion, our results indicate that T3 can stimulate the transcription of the UCP gene and amplify the effect of cAMP acting directly on the gene. The presence of two functional TREs in a location critical to the control of the gene supports the importance of thyroid hormone for its expression and suggests the potential for interactions at the gene level that may explain the complexity of UCP regulation in vivo. PMID- 7867555 TI - Roles of estrogen, progesterone, and gonadotropin-releasing hormone (GnRH) in the control of pituitary GnRH receptor gene expression at the time of the preovulatory gonadotropin surges. AB - Pituitary GnRH receptor (GnRH-R) messenger RNA (mRNA) levels are regulated dynamically during the rat estrous cycle. GnRH-R mRNA levels increase 3-fold on the morning of proestrus and remain elevated throughout the gonadotropin surges, after which they decline rapidly. Because the day of proestrus is characterized by complex changes in the steroidal milieu and increased release of hypothalamic peptides such as GnRH, a series of in vivo steroid replacement and in vitro perifusion studies was used to assess the relative contributions of estrogen (E), progesterone (P), and GnRH to the induction and decline of GnRH-R gene expression during the gonadotropin surges. Steroid replacement studies in ovariectomized (OVX) E-primed rats demonstrated that GnRH-R mRNA levels were elevated before and during the E-induced LH surge (1000-1800 h). Receptor mRNA levels declined after the peak of the LH surge and were significantly lower by 2000 h. Pentobarbital treatment, which inhibits hypothalamic input and the LH surge, prevented the gonadotropin surge-associated increase in GnRH-R mRNA levels in E-primed OVX rats. Although GnRH-R mRNA levels did not change throughout the day of experiments in OVX unprimed rats, treatment with pentobarbital significantly reduced GnRH-R mRNA expression in these animals. P treatment of E-primed OVX rats had no significant effect on GnRH-R mRNA expression during the LH surge, but significantly reduced mRNA levels immediately after the LH surge (2000 h). Data from in vitro perifusion experiments using either metestrous or proestrous pituitary glands demonstrated that pulsatile GnRH up-regulates the expression of its own receptor mRNA at both estrous cycle stages. Based on these results, we conclude that enhanced GnRH-R mRNA expression observed on the day of proestrus is largely due to the actions of E, exerted indirectly via hypothalamic routes (presumably through enhanced GnRH secretion). Furthermore, preovulatory P secretion may account for the rapid decline in GnRH-R mRNA levels observed on the evening of proestrus. PMID- 7867556 TI - Estradiol and tamoxifen interactions with thyroid hormone in the ovariectomized thyroidectomized rat. AB - Receptors for estrogens and thyroid hormone (T3) have related DNA-binding domains that interact with closely related DNA target sequences which enable transcriptional control. In vitro molecular studies have raised the possibility that estrogen and T3 receptors may compete for binding to certain DNA target sites (cross-talk). However, there have been no physiological studies evaluating the abilities of estrogens or T3 to mimic or inhibit each other in vivo in a manner consistent with a mechanism involving receptor cross-talk. To address this issue, the effects of estradiol, tamoxifen (an antiestrogen), and T3 were studied in an ovariectomized-thyroidectomized rat model designed to minimize hormone interplay occurring via neuroendocrine or pharmacokinetic mechanisms. The T3 responses examined included induction of GH, somatic growth, and hepatic malic enzyme, and suppression of TSH secretion. The estrogen responses examined included induction of pituitary kallikrein, PRL, and uterine weight; increases in serum triglycerides; and suppression of LH secretion. Estradiol and tamoxifen acted as partial T3 agonists on GH induction, with agonist or antagonist effects depending upon T3's presence. Estradiol and tamoxifen acted as pure T3 antagonists on T3 induction of somatic growth and malic enzyme. Similarly, estradiol blocked T3-evoked decreases in bone mineral density and had no effect on bone in T3's absence. In contrast, estradiol or tamoxifen did not alter T3 feedback inhibition of TSH release or T3 induction of PRL. T3 partially mimicked estrogen actions to suppress LH, but did not mimic or inhibit other estrogen responses. Interestingly, the effect of estradiol and tamoxifen to increase serum triglycerides was totally T3 dependent even though T3 tended to decrease triglyceride levels. The results indicate that physiological effects of estrogens on GH, somatic growth, bone, malic enzyme, and serum triglycerides exhibit properties suggestive of a mechanism involving cross-talk with T3 receptors. Tamoxifen fully mimicked the effects of estradiol arising by an apparent antagonism of T3 actions, but acted as an antiestrogen in other responses. PMID- 7867557 TI - Immunological detection of membrane-associated human luteinizing hormone correlates with gene expression in cultured human cancer and fetal cells. AB - We have demonstrated the expression of membrane-associated hCG and its subunits and fragments by cells from 78 human cancer cell lines of different types and origins, indicating that such expression is a common phenotypic characteristic of cultured human malignant cells. Because human (h) LH beta has 80% homology with hCG beta and is coded by one of the seven genes in the gene cluster located in chromosome 19, it was important to determine whether hLH and its beta-subunit are also expressed as membrane-associated proteins by cells from human cancer cell lines. Thus, 11 cancer cell lines of different types and origins were adapted to grow in serumless medium, with Nutridoma-HU or SP as serum substitute, and analyzed by flow cytometry using two monoclonal antibodies directed to different conformational epitopes of intact hLH and a monoclonal antibody reacting with an epitope of hLH beta-free. The cells were also analyzed simultaneously for the expression of hCG and its subunits and fragments. Determination of translatable levels of hLH beta and hCG beta messenger RNAs (mRNAs) was performed in cells from some of the cancer cell lines, including the JEG-3 choriocarcinoma cell line, and in cells from a human fetal lung cell line. The analytical flow cytometry studies showed that in addition to the expression of membrane associated hCG in all of its forms, expression of membrane-associated intact (holo) hLH and its free beta-subunit occurred in every case. These findings were corroborated by the presence of translatable levels of hLH beta and hCG beta mRNAs in all of the cancer cell lines analyzed, indicating that the expression of these membrane-associated glycoproteins is a phenotypic characteristic of human cancer cells and that the activation of the hCG beta-hLH beta gene cluster is nonselective. The presence of translatable levels of hCG beta-hLH beta mRNAs in the cultured human fetal lung cells punctuates once more the in vivo and in vitro biochemical similarities between fetal and cancer cells. PMID- 7867558 TI - The 5'-flanking region of the ovine follicle-stimulating hormone-beta gene contains six progesterone response elements: three proximal elements are sufficient to increase transcription in the presence of progesterone. AB - Progesterone (P4) can alter the synthesis and secretion of FSH from pituitary gonadotropes of sheep. In this study, the 5'-flanking region (4.7 kilobases) of the ovine FSH beta gene was tested for binding by human progesterone receptors (hPR), using an immunoprecipitation technique. Three fragments were bound by hPR. Competition experiments using homologous and heterologous DNA fragments revealed this binding to be specific and of high affinity (Kd = 1.2-47 nM). The fragment sequences were screened for potential P4 response elements (PREs). Six PRE-like elements were found among the three immunoprecipitated fragments. Band shift experiments discerned that each of these PRE-like sequences could be bound by hPR. In functional studies, each of the PRE-like elements could enhance the expression of a reporter gene driven by a heterologous promoter in a hormone dependent manner. The 5'-flanking region of the ovine FSH beta gene was tested for P4 responsiveness using a luciferase reporter. In the presence of P4, there was a 2- to 3-fold increase in luciferase activity when the entire 4.7 kilobases of the 5'-flanking sequence were present, whereas no increase was seen in a construct that contained only 84 basepairs 5' to the transcription start site. This effect on transcription was dose dependent for P4. Deletion studies revealed that the three PRE-like elements closest to the transcription start site (-250 to -137) were sufficient to create the hormone-dependent enhancement. These results indicate that the 5'-flanking sequence of the ovine FSH beta gene contains sequences capable of being bound by hPR and may be responsible for the effects of P4 on FSH beta synthesis and secretion. This study is the first to show binding and function of PR for a gonadotropin gene. PMID- 7867559 TI - Acute, oral ethanol administration suppresses episodic growth hormone secretion in the male rat. AB - The effect of single dose ethanol administration on GH secretion was studied in young adult male rats bearing indwelling gastric and right-atrial cannulas. Rats (nonfasted) received saline or ethanol (1, 2, 3, or 4 g/kg) via gastric cannula 2h before the onset of the daily dark period; blood was sampled every 15 min for 5 h. Each rat served as its own control, receiving saline and one ethanol dose separated by 2-3 days. Plasma samples were assayed for ethanol, GH, and testosterone. On saline days, all rats showed typical, episodic peaks of GH in plasma. This pattern was unaffected by ethanol at 1 g/kg (peak plasma ethanol approximately 65 mg/100 ml). Ethanol at 2 g/kg caused a rapid, marked, but not total suppression of plasma GH levels (peak plasma ethanol approximately 140 mg/100 ml), whereas at doses of 3 or 4 g/kg ethanol, a total suppression of GH secretion occurred (peak plasma ethanol approximately 190 and 240 mg/100 ml, respectively). Plasma testosterone levels showed a similar dose-sensitivity to ethanol. The threshold for GH suppression appears to be around 100 mg/100 ml plasma ethanol and is sustained throughout the time period examined, despite falling ethanol levels. PMID- 7867560 TI - Activity of a novel nonpeptidyl growth hormone secretagogue, L-700,653, in swine. AB - L-700,653 is a potent nonpeptidyl GH secretagogue consisting of a benzolactam structure: (4'-[[3(R)-[[3-[(2(S),3-dihydroxypropyl) amino]3-methyl-1 oxobutyl]amino]2,3,4,5-tetrahydro-2-oxo-1H-1-benzaze pin- 1-yl]methyl][1,1' biphenyl]2-carboxamide hydrochloride). When administered sc by a Medi-Jector device at 0, 0.003, 0.01, 0.03, and 0.1 mg/kg BW to male castrated swine (approximately 50 kg BW), L-700,653 stimulated dose-related increases in peak plasma GH concentrations by 20% (P = NS), 150% (P = NS), 250% (P < 0.05), and 340% (P < 0.05), respectively, over the saline vehicle control value (11.3 +/- 6.5 ng/ml) and stimulated increases in GH areas under the curve (AUCs) by 10% (P = NS), 30% (P = NS), 90% (P < 0.05), and 100% (P < 0.01), respectively, over the saline vehicle control value (799 +/- 145 ng/min.ml). After sc administration of L-700, 653, there were no significant changes in plasma LH levels. Subcutaneous dose of 0.03 or 0.1 mg/kg increased plasma cortisol AUCs by 60% (P = NS) and 150% (P < 0.03) over the control value (2461 +/- 935 ng/min.ml) and increased cortisol peaks by 80% (P = NS) and 200% (P < 0.01), respectively, over the control value (38.3 +/- 12.3 ng/ml). Repeated sc administration of L-700,653 (0.03 or 0.1 mg/kg) at 0800, 1400, and 2000 h daily over 3 days consistently increased mean GH peak and GH AUC at each treatment period, with minimal and maximal increases of 40% and 190% in GH peak level at the 0.03 mg/kg dose and 100% and 400% increases in GH peak level at the 0.01 mg/kg dose, respectively. Continuous i.v. infusion of L-700,653, at either 0.01 or 0.1 mg/kg BW.h over a 180-min period, increased GH AUCs by 60% (P = NS) or 470% (P < 0.01) and GH peaks by 190% (P = NS) or 1520% (P < 0.01), respectively, over the control value (589 +/- 313 ng/min.ml; 7.0 +/- 11.1 ng/ml). After a 180- to 300-min saline infusion, an iv bolus dose of 0.1 mg/kg L-700,653 resulted in GH responses inversely proportional to the previous infusion dose, i.e. 0, 0.01, or 0.1 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7867561 TI - Inhibition of growth hormone-releasing factor production in mouse placenta by cytokines using gp130 as a signal transducer. AB - The aim of this study was to investigate whether mouse placenta produces mature mouse GHRF (mGHRF) and whether cytokines regulate placental mGHRF production. Using Sephadex G-50 gel filtration chromatography and reverse phase HPLC, we identified immunoreactive mGHRF in acid-ethanol extract of placental tissues, which had chromatographic characteristics identical to those of hypothalamic mature mGHRF peptide. The major peak of immunoreactive GHRF in the medium from cultured placental cells was resolved by HPLC at a fraction identical to hypothalamic mature mGHRF. Interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), and oncostatin-M, which all use gp130 as a signal transducer, significantly inhibited mGHRF secretion by cultured placental cells. However, IL 1 alpha and tumor necrosis factor-alpha had no effect on mGHRF secretion. Antibodies to IL-6 or IL-6 receptor completely blocked the inhibitory effect of IL-6 on mGHRF secretion. Anti-LIF, and oncostatin-M inhibited the expression of mGHRF messenger RNA. These results suggest that mouse placenta produces and releases the mature mGHRF, which is indistinguishable by chromatographic criteria from that produced by the hypothalamus, and that signals through gp130 lead to the inhibition of mGHRF production and release in the mouse placenta. PMID- 7867562 TI - Effects of the phospholipase-C inhibitor, U73122, on signaling and secretion in pituitary gonadotrophs. AB - The effects of inhibition of phosphoinositide hydrolysis by U73122 [1-(6-[17 beta 3-methoxyestra-1,3,5- (10) triene-17-yl] amino/hexyl) 1H-pyrroledione] and neomycin on agonist-stimulated intracellular signaling and secretory responses were analyzed in cultured pituitary cells and alpha T3-1 gonadotrophs. GnRH (100 nM)- and endothelin-1 (ET-1; 100 nM)-induced inositol (1,4,5)-trisphosphate and diacylglycerol formation in normal cells and immortalized gonadotrophs were reduced by U73122 in a concentration-dependent manner, with IC50 values of about 2 microM and complete inhibition at 10 microM U73122. Neomycin also reduced GnRH- and ET-induced inositol phosphate production in both cell types. Agonist-induced intracellular Ca2+ responses were also inhibited in both cell types by U73122 and neomycin at the same concentrations that inhibited their inositol phosphate responses. In cultured pituitary cells, agonist-induced LH release was inhibited by U73122 and neomycin in a dose-dependent manner. In perifused pituitary cells, U73122 completely inhibited GnRH- and ET-1-induced LH release, but after 10 min caused a progressive and substantial increase in basal LH release. In static cultures, U73122 inhibited agonist-induced LH response at low concentrations (up to 3 microM), but stimulated LH release at higher concentrations due to direct activation of exocytosis by the compound. When added alone, U73122 caused a concentration-dependent increase in LH release with an EC50 of about 7 microM and a maximum response similar that that elicited by GnRH. The stimulatory action of U73122 on LH release was not reduced in the absence of extracellular Ca2+. In contrast to cultured pituitary cells, alpha T3-1 gonadotrophs showed only constitutive exocytosis that was not affected by either neomycin or U73122. These results demonstrate that GnRH and ET(A) receptors are coupled to the phosphoinositide/Ca2+ transduction system in pituitary gonadotrophs, and provide evidence for the dependence of agonist-regulated exocytosis on this signaling pathway. The ability of U73122 to stimulate LH release could reflect an additional action of the compound at late steps in the exocytic pathway. PMID- 7867563 TI - Identification of a rat osteocalcin promoter 3',5'-cyclic adenosine monophosphate response region containing two PuGGTCA steroid hormone receptor binding motifs. AB - In MC3T3-E1 mouse osteoblastic cells, the adenylate cyclase activator forskolin increases osteocalcin (OC) mRNA levels. We have analyzed the effects of forskolin and 8-Br cAMP on the transcriptional activity of the rat OC promoter (with luciferase reporter) in MC3T3-E1 cells. Both forskolin and 8-Br cAMP activate the rat OC promoter 2- to 5-fold. By 5' deletion analysis, we have mapped the cAMP response to the region -121 to -92. The 48-base pair rat OC promoter region -121 to -74 (hence denoted ROCRR) can confer cAMP responsiveness to an unresponsive heterologous minimal promoter. Crude nuclear extracts prepared from MC3T3-E1 cells form three complexes with the ROCRR by gel shift analysis. No specific change in nuclear factor binding in response to cellular forskolin treatment could be demonstrated. Intriguingly, two nuclear factor complexes bound to the ROCRR also recognized the thyroid hormone response element palindrome (AGGTCATGACCT) but did not bind the classic cAMP (TGACGTCA) or glucocorticoid (AGAACANNNTGTTCT) response elements. The rat OC promoter possesses two directly repeated PuGGTCA steroid hormone response element hexamer motifs (bottom strand) in the region -114 to -93 within the ROCRR, separated by a 10 nucleotide spacer. Oligos encoding the individual rat OC hexamer sites compete for the ROCRR DNA:protein complexes recognized by the thyroid hormone response element palindrome. Removal of the up-stream hexamer site by 5' deletion (-121 to -100) in the context of the native OC promoter abrogates cAMP responsiveness. Taken together, these data suggest that this novel rat OC cAMP response region assembles a protein:DNA complex containing member(s) of the steroid hormone receptor superfamily. Transcriptional activity, but not DNA binding, is regulated by cAMP. PMID- 7867565 TI - Deprenyl reinitiates estrous cycles, reduces serum prolactin, and decreases the incidence of mammary and pituitary tumors in old acyclic rats. AB - The purpose of this study was to investigate the effects of long term treatment with deprenyl, a monoamine oxidase-B inhibitor, on estrous cyclicity, serum PRL, incidence of mammary and pituitary tumors, and monoamine metabolism in the medial basal hypothalamus (MBH) and striatum (ST) of old female rats. Acyclic female Sprague-Dawley rats (15-16 months old) were treated sc with 0, 0.25, or 2.5 mg deprenyl/kg BW.day for more than 8 months. Body weight and food intake were measured every week, and the estrous cycles and development of mammary tumors were monitored throughout the treatment period. At the end of the treatment period, the concentrations of catecholamines, serotonin, and their metabolites in the MBH and ST were determined by HPLC with electrochemical detection. The wet weights of the pituitary, heart, liver, lung, kidney, adrenals, uterus, and ovaries were recorded. Trunk blood was collected for measurement of serum PRL concentrations by RIA. Deprenyl treatment temporarily reestablished estrous cycles in most of the rats. The incidence of pituitary and mammary tumors was markedly reduced in the deprenyl-treated rats compared with that in the saline treated control rats. Deprenyl had no significant effect on the weights of internal organs. The high dose of deprenyl (2.5 mg/kg) decreased serum PRL concentrations significantly. There were no significant differences in body weight or food intake between the control and deprenyl-treated groups. Deprenyl decreased the concentrations of the monoamine metabolites, dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid, in both the MBH and ST. It had no effect on the concentrations of norepinephrine and dopamine in the MBH, but significantly increased norepinephrine concentrations in the ST and serotonin concentrations in both the MBH and ST (P < 0.05). It is concluded that deprenyl treatment exerted these effects via suppression of monoamine metabolism. PMID- 7867564 TI - Ligand requirements of the human corticotropin-releasing factor-binding protein. AB - CRF-binding protein (CRF-BP), identified as a 37-kilodalton human serum protein, binds human (h) CRF (Kd = 0.17 +/- 0.01 nM) and blocks hCRF's ability to stimulate ACTH release by pituitary cells in vitro. The present study examines ligand requirements of CRF-BP by testing the affinity of recombinant CRF-BP for synthetic analogs of CRF and peptides in the CRF family. The relative affinities of various fragments of hCRF or related peptides for CRF-BP indicate that residues 9-28 are crucial for ligand binding. CRF-BP binds human/rat CRF and urotensin-I with high affinity, sauvagine with moderate affinity, and ovine (o) CRF with low affinity. The marked difference in the affinity of CRF-BP for oCRF (Ki = 1100 +/- 97 nM) compared to hCRF (Ki = 0.17 +/- 0.01 nM), when considered with the importance of the central domain, suggests that amino acids 22, 23, and/or 25 are critical for binding. Altering oCRF residues 22, 23, or 25 individually or collectively to match those of hCRF increases the affinity of CRF BP for these ligands; [Ala22, Arg23, Glu25]oCRF, in which all three of these central amino acids are substituted by their hCRF counterparts, binds CRF-BP with an affinity equal to that of hCRF. CRF-BP has differential affinities for CRF receptor antagonists, binding alpha-helical CRF-(9-41) with high affinity and [D Phe12, Nle21,38]hCRF-(12-41) with low affinity. Thus, the structural requirements for binding to CRF-BP can clearly be distinguished from those for CRF receptor recognition of both agonists and antagonists. Peptides such as hCRF-(9-33), with low biological activity but which retain high affinity for the binding protein, can competitively override the effects of CRF-BP to block CRF-induced ACTH secretion, raising the possibility that whereas endogenous CRF-BP serves to limit the distribution or duration of action of CRF, specific pharmacological inhibitors of the ligand-binding protein interaction might be used to therapeutically elevate free CRF levels. PMID- 7867566 TI - Translational regulation of the gonadotropin-releasing hormone receptor in alpha T3-1 cells. AB - Prolonged exposure of the GnRH receptor to high concentrations of GnRH leads to receptor down-regulation. The role of altered receptor biosynthesis in this agonist-induced receptor down-regulation was investigated in the mouse gonadotrope cell line, alpha T3-1 cells. After exposure to 1 microM GnRH for 24 h, the number of GnRH receptor-binding sites in alpha T3-1 cells decreased to 25 +/- 6% of the control levels. No corresponding changes were observed in GnRH receptor messenger RNA (mRNA) using either quantitative ribonuclease protection/solution hybridization assay or Northern blot analysis. However, when the ability of this RNA to direct the synthesis of functional GnRH receptors was examined by quantitative assessment of the voltage clamp response in Xenopus oocytes, GnRH-induced currents in oocytes injected with RNA isolated from down regulated cells was reduced to 40 +/- 13% of the response obtained after the injection of RNA from control alpha T3-1 cells. Thus, although GnRH receptor mRNA levels were not altered, the ability of cellular RNA isolated from alpha T3-1 cells to direct the synthesis of functional GnRH receptors was regulated in concert with receptor binding. To investigate the possibility that GnRH receptor mRNA translational efficiency was reduced, the distribution of polyribosome associated GnRH receptor mRNA was studied. Polyribosome-associated mRNA was separated by linear sucrose gradient, and GnRH receptor mRNA distribution was determined by ribonuclease protection assay. GnRH receptor mRNA distribution shifted from the largest to smaller polyribosome and monosome fractions in cells exposed to GnRH compared to controls. The weighted mean of GnRH receptor mRNA distribution among eight fractions shifted from fraction 5.924 +/- 0.06 in control polysomes to fraction 5.45 +/- 0.219 for polysomes from down-regulated cells (P < 0.05). These results demonstrate that GnRH receptor down-regulation is accompanied by decreased GnRH receptor mRNA translation in the absence of any change in GnRH receptor mRNA levels. These data suggest that decreased efficiency of GnRH receptor mRNA translation contributes to the down-regulation of this receptor in alpha T3-1 cells. PMID- 7867567 TI - Kallikrein gene family expression in the rat ovary: localization to the granulosa cell. AB - The glandular or tissue kallikreins are a multigene family of serine proteases, of which 13 genes (rKLK1-13) have been identified in the rat and are expressed in a wide variety of tissues. Kallikrein-like enzyme activity has been detected during the periovulatory period in the gonadotropin-primed immature female rat ovary and suggested to play a role in the inflammatory-like response at ovulation. In this study, we examined whether this enzyme activity was due to local expression of a rat KLK gene family member. Ovarian RNA, prepared from gonadotropin-treated animals, was assessed for rKLK gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) with universal rKLK primers derived from highly conserved regions in the rat KLK genes. Southern blot analysis of the RT-PCR products, using oligonucleotide probes specific for the individual genes, indicated that five rKLK gene family members, rKLK1 (encoding true kallikrein), rKLK3, rKLK7, rKLK8, and rKLK9, were expressed at varying levels in the ovaries of both untreated control and gonadotropin-treated immature female rats. The identities of these five rKLK messenger RNAs were further confirmed by DNA sequence analysis of the PCR products. In situ hybridization of gonadotropin-treated ovaries localized rKLK3 and rKLK7 gene expression to the luteinizing granulosa cells of periovulatory follicles. In an enriched population of nonluteinizing granulosa cells prepared from estrogen-primed animals, we also demonstrated rKLK3, rKLK7, rKLK9, and rKLK12 (but not rKLK1 or rKLK8) expression, whereas all six genes were expressed in the ovaries of these animals. In summary, we have reported the expression of six KLK gene family members in the rat ovary and localized this expression primarily to the granulosa cell. The potential roles of these enzymes in ovulation or other aspects of ovarian, particularly granulosa cell, function are yet to be elucidated. PMID- 7867568 TI - 1 alpha,25(OH)2-vitamin D3 analog structure-function assessment of intestinal nuclear receptor occupancy with induction of calbindin-D28K. AB - 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] has been shown to generate biological responses via both genomic and nongenomic pathways. In previous studies concerning the mechanism of 1 alpha,25(OH)2D3-stimulated rapid intestinal transport of Ca2+, a process termed transcaltachia, we assessed the ability of seven analogs of 1 alpha,25(OH)2D3 to initiate transcaltachia in the vitamin D replete chick and bind in vitro to the classical nuclear chick intestinal receptor for 1 alpha,25(OH)2D3 (VDR). Two groups of analogs were found, one able to stimulate transcaltachia and the other able to bind to the VDR. In the present study, we have examined both the genomic effect of these analogs in the intestine of vitamin D-deficient chicks and their in vitro binding to vitamin D binding protein. It was found that analogs known to bind effectively to the nuclear receptor in vitro could achieve a significant occupancy of the VDR in vivo and stimulated calbindin-D28K messenger RNA and protein synthesis. In contrast, those analogs that were good agonists of transcaltachia were ineffective either in occupying the VDR in vitro or in stimulating in vivo calbindin-D28K messenger RNA and protein synthesis. These differences are consistent with our hypothesis that there may be two receptors for 1,25-(OH)2D3 with differing ligand binding domains, one being the classical nuclear VDR and the second a membrane receptor associated with transcaltachia. PMID- 7867569 TI - Ames dwarf mice exhibit somatotrope commitment but lack growth hormone-releasing factor response. AB - Ames dwarf mice have a recessive defect that results in affected mice (df/df) with extremely hypocellular anterior pituitaries that generally lack somatotropes, lactotropes, and thyrotropes. We report detection of rare foci of GH+ cells by immunocytochemistry, suggesting that some commitment to a somatotrope cell fate can occur in the pituitaries of df/df mice. A role for GHRF in regulating somatotrope proliferation is well documented. It has been shown that expression of human GHRF (hGHRF) in transgenic mice resulted in increased somatic growth and somatotrope hyperplasia over nontransgenic littermates. To assess whether overexpression of GHRF during ontogeny might elicit a physiological response in df/df mice, we generated df/df mice expressing the hGhrf transgene. Although the somatic growth of transgenic df heterozygotes was dramatically increased over that of nontransgenic littermates, df/df mice were refractory to excess GHRF. No GHRF receptor (Grfr) transcripts were detectable in df/df fetuses or adult mice by in situ hybridization analysis. In contrast, Grfr expression is detected by e16.5 in df/+ mice. The lack of Grfr expression in df/df fetuses may account for their lack of response to GHRF and implies that the df gene product is required before e16.5. PMID- 7867570 TI - Degradation of gonadotropin beta-subunits retained in the endoplasmic reticulum of the gonadotropes of castrated rats. AB - LH and FSH are composed of a common alpha-subunit and a noncovalently associated hormone-specific beta-subunit. Unassociated beta LH and beta FSH can be retained in the cisternae of endoplasmic reticulum (ER). This phenomenon is particularly evident in gonadotropes of castrated animals where beta-subunits are expressed in larger amounts than the alpha-subunit. Because little was known about the fate of the gonadotropin beta-subunits retained in the ER, we carried out immunocytochemical studies on ultrathin frozen sections of anterior pituitaries of castrated rats. After castration, the intracellular levels of the beta subunits were found to increase more than that of the alpha-subunit. When the subcellular localization of the alpha- and beta-subunits and secretogranin II (a regulated secretory protein present in the secretory granules of gonadotropes of many species) was investigated by double immunoelectron microscopy, both gonadotropin subunits were colocalized in secretory granules with secretogranin II. However, only the beta-subunits, not the alpha-subunit and secretogranin II, were localized in the dilated cisternae of the ER as well as in irregularly shaped vacuoles. Using markers for the endoplasmic reticulum, the prelysosomal compartment and lysosomes (cathepsin D and lgp120), we found that these vacuoles correspond to a degradative compartment with two types of intermediates: 1) one with small amounts of lgp120, and cathepsin D preferentially localized at the periphery of a central dense matrix; and 2) the other with larger amounts of lgp120, and cathepsin D present all over the matrix of the vacuole. These vacuoles do not derive from autophagy because vesicles surrounded by a double or multilamellar membrane containing profiles of ER cisternae together with small amounts of the cytoplasm were never detected. Moreover, they do not correspond to crinophagic bodies because the latter contained beta-subunits as well as alpha subunit and SgII. Our data indicate that gonadotropin beta-subunits, probably retained as unassociated subunits in the endoplasmic reticulum of castrated rat gonadotropes, undergo degradation in vacuoles that acquire lysosomal enzymes. This process appears different from the classical autophagy, but similar to the nonautophagic pathway for the diversion to lysosomes of the intracisternal granules accumulated in the ER of hyperstimulated thyrotropes. PMID- 7867571 TI - Calcitonin down-regulates immediate cell signals induced in human osteoclast-like cells by the bone sialoprotein-IIA fragment through a postintegrin receptor mechanism. AB - Calcitonin (CT) is a peptide hormone that interacts with the cAMP-and phospholipase C-associated CT receptor subtypes. We investigated whether CT modulates the interaction of human tumoral osteoclast-like (GCT23) cells with a protein of the bone matrix, bone sialoprotein-II (BSP-II). Single GCT23 cells loaded with the intracellular Ca2+ indicator fura-2 were treated with the maximal active dose (300 micrograms/ml) of the 18-mer Arg-Gly-Asp (RGD)-containing BSP IIA fragment, and the cytosolic free Ca2+ concentration ([Ca2+]i) was measured by dual wavelength microfluorometry. BSP-IIA stimulated an elevation in [Ca2+]i, consisting mainly of a peak, followed by a rapid return toward baseline. Pretreatment with CT induced a modest elevation of [Ca2+]i. However, CT significantly inhibited the response to BSP-IIA in a dose-dependent manner. Maximal inhibition (90% vs. untreated) was observed in the micromolar range. The intracellular mechanisms leading to this effect were investigated by pretreatment of GCT23 cells with the cAMP permeant analog, (Bu2)cAMP, and the protein kinase-C activating agent, 12-O-tetradecanoylphorbol 13-acetate. Similar to CT, both agents inhibited the response to 300 micrograms/ml BSP-IIA. The effect induced by CT was specific, because an increase in the extracellular Ca2+ concentration, which is also known to inhibit bone resorption, failed to modify the ability of BSP-IIA to alter [Ca2+]i in GCT23 cells. To investigate whether the CT-induced alteration of BSP-IIA-dependent cell signals was due to a modification in the synthesis of cell surface receptors (integrins) for the extracellular matrix macromolecules, 1-h CT-treated [35S]methionine metabolically labeled GCT23 cell lysates were immunoprecipitated with anti-alpha 3-, -alpha v-, -beta 1-, and beta 3-integrin subunit antibodies. Autoradiography demonstrated that 10(-7)-10( 6) M CT did not alter new synthesis of the alpha v beta 3 and the alpha 3 beta 1 receptors. Similarly, CT did not affect surface expression of these receptors, assessed by enzyme-linked immunosorbent assay. Finally, no alteration of the adhesion rate and spreading of GCT23 cells onto BSP-IIA-coated substrates was observed. This indicates that CT-induced down-regulation of immediate cell signals prompted by BSP-IIA in GCT23 cells is a postintegrin receptor event. PMID- 7867572 TI - Mouse insulinoma beta TC3 cells express prodynorphin messenger ribonucleic acid and derived peptides: a unique cellular model for the study of prodynorphin biosynthesis and processing. AB - The tumor cell line beta TC3 has been established from insulinomas derived from transgenic mice carrying a hybrid insulin promoter-simian virus-40 tumor antigen gene. The beta TC3 cells express high steady state levels of proinsulin messenger RNA (mRNA). In this same cell line, we describe in the present study high expression levels of prodynorphin (pro-Dyn) mRNA and its derived peptides. By Northern blot analysis, the screening of 23 cell lines of endocrine (n = 10) and of nonendocrine (n = 13) origin revealed the presence of high levels of the 2.6 kilobase pro-Dyn transcript only in beta TC3 cells. The beta TC3 cells expressed levels of pro-Dyn mRNA comparable to those in rat tissues expressing pro-Dyn. Chromatographic and radioimmunological studies showed that pro-Dyn mRNA was translated and fully processed into opioid peptides with leucine-enkephalin (Leu Enk)-extended sequences [dynorphin-A-(1-8), dynorphin-B-(1-13), and alpha-neo endorphin]. The expression of the prohormone convertases was also examined in beta TC3 cells by Northern blot analysis. In addition to the ubiquitously expressed furin, beta TC3 cells have abundant levels of prohormone convertase-1 (PC1) and PC2 mRNAs, but undetectable levels of PACE4 or PC5 mRNAs. Incubation of beta TC3 cells with 8-bromo-cAMP for 24 h stimulated 3-fold both the pro-Dyn mRNA levels and the secretion of opioid peptides. In contrast to pro-Dyn mRNA, furin, PC1, and PC2 mRNA levels were not affected by 8-bromo-cAMP. The beta TC3 cells constitute a unique model to elucidate the biosynthetic pathway of pro-Dyn processing, to identify the proteolytic enzymes responsible for the production of pro-Dyn end products, and to assess the potential role of opioid peptides in the regulation of pancreatic function. PMID- 7867573 TI - Effects of epidermal growth factor on the tyrosine phosphorylation of mitogen activated protein kinases in monolayer cultures of porcine granulosa cells. AB - We have examined porcine granulosa cells (pGCs) for the presence of immunodetectable mitogen-activated protein (MAP) kinases (extracellular signal regulated kinases, ERK) and have further studied the effects of epidermal growth factor (EGF) on the activation of these kinases. Cell lysates prepared from untreated monolayer cultures of pGCs were subjected to Western immunoblotting analysis using monoclonal antibodies to ERK1, ERK2 and pan-specific ERK. MAP kinases were detected having mol wts of 87K (ERK87), 54K (ERK54), 44K (ERK1), and 42K (ERK2). Treatment of pGCs with increasing concentrations (1-10 ng/ml) of EGF for 10 min resulted in electrophoretic mobility shifts of ERK1 and ERK2 suggesting hyperphosphorylation. Immunoprecipitation with an antiphosphotyrosine antibody (PY20), followed by Western analysis using pan-ERK, revealed a marked concentration-dependent increase in tyrosine phosphorylation of ERK2 in response to EGF treatment. The mobility shift and tyrosine phosphorylation of ERK2 was observed as early as 1 min after treatment with 10 ng/ml EGF. In-gel myelin basic protein (MBP) kinase assays revealed significant MBP kinase activity associated with ERK1 and ERK2 in total cell lysates and ERK2 in PY20 immunoprecipitates. Although ERK1 displayed a moderate mobility shift in response to EGF, tyrosine phosphorylation of this MAP kinase was not appreciably increased by EGF. Furthermore, PY20 immunoprecipitates demonstrated minimal MBP kinase associated with ERK1 in response to EGF treatment. Electrophoretic migration, tyrosine phosphorylation, and MBP kinase activity of the ERK54 and ERK87 was not effected regardless of EGF concentration or duration of treatment. These data demonstrate for the first time that pGCs contain immunodetectable MAP kinases. EGF, in a concentration- and time-dependent manner, increases tyrosine phosphorylation and MBP kinase activity (i.e. activation) of ERK2, and to a lesser degree ERK1, suggesting that the activation of MAP kinase may mediate the mitogenic action of EGF in pGCs. PMID- 7867574 TI - Nerve growth factor promotes the differentiation of pituitary mammotroph cells in vitro. AB - It is well known that the differentiation of somatotroph cells is dependent on GRF. The extracellular signals that direct the initial proliferation and differentiation of mammotroph cells during pituitary development, however, have remained elusive. In the present study we first report that somatomammotroph and mammotroph cells present in early postnatal rat pituitary cultures express the receptor for nerve growth factor (NGF) and contain NGF. In addition, we demonstrate that endogenous NGF supports the proliferation and terminal differentiation of mammotroph cells during postnatal in vitro maturation. Early postnatal rat pituitary cells were cultured for 1-12 days, double stained with antibodies to PRL and GH, and analyzed by fluorescence-activated cell sorting. Mature mammotroph cells were generated in culture as shown by 1) the increase in PRL production, 2) the spreading of cells secreting only PRL in relation to those producing both PRL and GH, and 3) the expression of D-2 receptors for dopamine. Exposure of cell cultures to NGF produced a remarkable increase in the rate of appearance of mammotroph cells and an increase in their abundance from 20 +/- 0.5% to 44 +/- 1%. Deprivation of secreted NGF by means of a specific antibody completely prevented the generation of mature mamotrophs. The fluorescence activated cell sorting analysis of cells grown in the presence of the antibody to NGF showed, in fact, that although the proportions of somatotrophs and somatomammotrophs were unchanged, that of mammotrophs was much lower than that in untreated cultures. We, thus, conclude that NGF is critical for generation of the mammotroph phenotype during pituitary maturation. PMID- 7867575 TI - Effects of activin A on deoxyribonucleic acid synthesis, iodine metabolism, and cyclic adenosine monophosphate accumulation in porcine thyroid cells. AB - We have recently shown the presence of activin A in human thyroid cells. To determine whether activin A affects the growth and function of the thyroid, we investigated its effects on DNA synthesis, iodine metabolism, and cAMP accumulation in cultured porcine thyroid cells. Activin A increased DNA synthesis. This effect was abolished by addition of follistatin but additively enhanced by epidermal growth factor. In contrast, activin A significantly reduced uptake and release of iodide by the thyroid and also TSH-induced cAMP accumulation but did not inhibit the cAMP accumulation induced by forskolin. These data indicate that activin A stimulates thyroid growth irrespective of cAMP accumulation and inhibits thyroid function. PMID- 7867576 TI - Ovarian inhibin subunit gene expression: regulation by gonadotropins and estradiol. AB - Inhibin and FSH maintain a dynamic inverse relationship throughout the rat estrous cycle. In particular, inhibin alpha- and beta A-subunit messenger RNAs (mRNAs) have been shown to be maximally expressed immediately after the midcycle gonadotropin surge, when both circulating estradiol (E2) and inhibin are also elevated. The current study was designed to investigate the regulation of inhibin subunit gene expression and secretion in vivo by recombinant human FSH (rhFSH) and estradiol. Initially, we determined if physiological levels of rhFSH regulated ovarian inhibin subunit gene expression and secretion. Hypophysectomized (HYPOX) adult female rats received hCG (10 IU, sc) and were then treated for 24 h with either rhFSH (0.5-20 IU every 6 h, i.v.) or saline. Hypophysectomy reduced inhibin subunit mRNAs as well as serum inhibin and estradiol. Although 0.5 IU rhFSH was ineffective in increasing inhibin subunit mRNAs, all doses between 2.5-20 IU increased inhibin subunit gene expression and inhibin secretion. Inhibin alpha-, beta A-, and beta B-subunit mRNAs were increased to a similar degree (3- to 5-fold) by all rhFSH doses of 5 IU or more. Similarly, serum E2 and inhibin were increased 2- and 3-fold, respectively, above HYPOX values after all doses of rhFSH of 5 IU or more. To investigate the role of a pure FSH signal in a physiological dose on inhibin subunit gene expression, HYPOX rats were given either rhFSH (5 IU, i.v., every 6 h for 24 or 48 h), hCG (10 IU, sc), or their combination. Neither gonadotropin when given alone altered inhibin subunit gene expression or serum E2 concentrations. Inhibin secretion rose in response to rhFSH alone, but not to hCG. The combination of hCG and rhFSH resulted in increased inhibin subunit mRNAs (3- to 5-fold) as well as circulating E2 and inhibin concentrations. We next studied the effects of E2 replacement in HYPOX rats at both physiological (serum approximately equal to 40 pg/ml) and higher doses (serum approximately equal to 800 pg/ml, to mimic intraovarian concentrations) in the presence or absence of exogenous gonadotropins (for 24 and 48 h). Although not as effective as gonadotropins, both E2 regimens increased inhibin alpha to a similar degree (2-fold), whereas beta-subunit mRNAs were unchanged at 24 h. Serum inhibin concentrations were increased only 48 h after high dose E2 treatments. As the actions of E2 and gonadotropins on alpha-subunit mRNA were not additive, E2 appears to mediate gonadotropin regulation of alpha subunit gene expression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7867577 TI - Prostaglandin E2 administered to fetal sheep increases the plasma concentration of adrenocorticotropin (ACTH) and the proportion of ACTH in low molecular weight forms. AB - This study investigated the effects of repeated short term (2-h) intrafetal infusions of prostaglandin E2 (PGE2) on ACTH and cortisol release in fetal sheep during late gestation (119-144 days). We compared the effects of administration of PGE2 (2 micrograms/min) into the fetal carotid artery or jugular vein. PGE2 infusion significantly (P < 0.001) increased fetal plasma immunoreactive (ir-) ACTH and cortisol concentrations regardless of the vessel used for administration. Saline infusion did not alter the concentrations of ir-ACTH or cortisol for the duration of the experiment. To compare the responses of fetal ir ACTH and cortisol to repeated intracarotid infusions of PGE2, the hormone data were grouped into five gestational age ranges (119-125, 126-130, 131-135, 136 140, and 141-145 days). Fetal ir-ACTH was stimulated by PGE2 infusion at all gestational ages studied; the greatest response was achieved at the earliest gestational age range, 119-125 days. PGE2 infusion preferentially stimulated the release of low mol wt ACTH [ACTH-(1-39); 60 min from the start of infusion] at all gestational ages (P < 0.01), but basal low mol wt ACTH did not increase with gestational age until after 140 days. Cortisol concentrations were increased within 30 min of infusion at all gestational ages studied. These results suggest that PGE2 may play a role in maintaining elevated ir-ACTH concentrations in the face of high levels of cortisol in fetal sheep before parturition. PMID- 7867578 TI - Role of nitric oxide on cardiac hormone secretion: effect of NG-nitro-L-arginine methyl ester on atrial natriuretic peptide and brain natriuretic peptide release. AB - Endocardial cells, like endothelial cells, release nitric oxide (NO) and may play a role in modulating the contractility of cardiac muscle. We have studied the effects of NG-nitro-L-arginine methyl ester (L-NAME), a selective NO synthase inhibitor, on basal and volume expansion-induced secretion of two cardiac hormones, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), in vivo. In conscious chronically cannulated rats, bolus injection of L-NAME at doses of 1, 3, and 10 mg/kg, iv, caused a dose-dependent increase in mean arterial pressure and sustained bradycardia, whereas right atrial pressure remained unchanged. The hemodynamic effects of L-NAME were reversed by simultaneous administration of L-arginine, a precursor of NO. Administration of 3 and 10 mg/kg L-NAME alone increased plasma levels of immunoreactive ANP (IR-ANP) from 30 +/- 5 to 52 +/- 9 pmol/liter and from 38 +/- 6 to 91 +/- 16 pmol/liter (P < 0.01), respectively, but had no effect on plasma levels of immunoreactive BNP (IR-BNP). The increase in plasma IR-ANP concentration in response to L-NAME infusions showed a positive linear correlation (P < 0.01) with the increase in mean arterial pressure and a negative correlation (P < 0.01) with the changes in heart rate. Acute volume expansion with 0.9% saline in conscious animals resulted in a 3.2-fold increase in plasma IR-ANP levels (from 35 +/- 7 to 113 +/- 15 pmol/liter; P < 0.01), but plasma IR-BNP levels did not change. In the rats pretreated with L-NAME, the relation between the changes from control in plasma IR-ANP and right atrial pressure shifted to the left; the absolute increases corresponding to the 3 mm Hg increase in right atrial pressure were 66 +/- 13, 76 +/- 15, 135 +/- 33, and 148 +/- 24 pmol/liter in the control and 1 mg/kg L-NAME, 3 mg/kg L-NAME-, and 10 mg/kg L-NAME-treated groups, respectively. The combined infusion of L-NAME and L-arginine attenuated the L-NAME-induced increase in ANP release. Our results show that L-NAME increases basal plasma IR-ANP levels and enhances stretch-induced ANP release, suggesting that secretion of ANP in response to volume load may be modulated by the locally released nitric oxide from the endothelium. Further, acute regulation of BNP secretion in response to inhibition of nitric oxide synthase and volume load differs from that of ANP. PMID- 7867579 TI - The fetal somatotropic axis during long term maternal undernutrition in sheep: evidence for nutritional regulation in utero. AB - Nutrition is a major determinant of the somatotropic axis during postnatal life. However, little is known about the response of the fetal somatotropic axis to nutritional limitation. From day 100 of gestation (term = 147 days), singleton bearing ewes were fed either ad libitum (control; n = 6) or 25% of the recommended energy and protein requirements (restricted; n = 7). Ewes and fetuses were chronically catheterized on day 110. On day 120, paired maternal and fetal blood samples were taken over a 6-h period at 15-min intervals. Forty-eight hours later, fetuses were given a 20-micrograms GRF bolus (i.v.), and samples were collected for 48 h. Undernourished mothers and fetuses had higher GH concentrations (P < 0.05). Although plasma GH profiles were independent in mothers and their fetuses, both maternal and fetal GH peak and nadir levels were increased (P < 0.05) by nutritional restriction, but the peak/nadir ratio and the number of pulses remained unaltered. Deconvolution analysis showed that the GH mass secreted per burst was higher in nutritionally restricted animals, whereas basal GH secretion and GH serum half-life were not influenced by undernutrition. Both maternal and fetal insulin-like growth factor-I levels were reduced (P < 0.01 and P < 0.05), whereas insulin-like growth factor-II concentrations were not influenced by the feed restriction. Fetuses from restricted mothers had higher peak GH concentrations after a GRF challenge (P < 0.001), but after correction The specific binding of [125I]ovine placental lactogen ([125I]oPL) or [125I]oGH to maternal or fetal hepatic microsomal membrane preparations was not changed by the maternal undernutrition. Maternal oPL concentrations showed considerable short term fluctuations, whereas fetal oPL levels revealed no major fluctuations. Mean maternal oPL levels tended (P < 0.06) to be elevated, whereas fetal oPL concentrations tended (P < 0.06) to be decreased in restricted animals. These results provide evidence that the somatotropic axis is functional in utero and suggest that the fetal somatotropic axis plays an active role during adaptation of the fetus to nutritional limitation. PMID- 7867580 TI - N-terminal-truncated recombinant analogs of bovine placental lactogen: interaction with human and rat growth hormone receptors and insulin-like growth factor-I secretion mediated by somatogenic receptors in rat hepatocytes. AB - Bovine placental lactogen (bPL) was found to be as potent as human GH (hGH) in its ability to bind to soluble full-size recombinant hGH-binding protein (hGHBP) and to membrane-embedded hGH receptor in intact IM-9 human lymphocytes. bPL was also capable of forming a 1:2 complex with hGHBP, although the structure of this complex was probably more compact than that with hGH. Removal of 13 amino acids from the N-terminus of bPL did not affect its ability to bind to hGHBP or hGH receptors in intact IM-9 cells. Its ability to form a 1:2 complex with hGHBP was, however, impaired, unlike that of a corresponding analog in which an L28F mutation has been simultaneously introduced. Truncation of 17 amino acids decreased its affinity toward both hGHBP and GH receptors on intact IM-9 lymphocytes and in liver rat microsomal fraction and inhibited the formation of 1:2 complexes with hGHBP. Simultaneous L28F mutation did not affect affinity toward hGHBP, but increased affinity toward rat liver GH receptors and restored affinity toward membrane-embedded hGH receptors in IM-9 lymphocytes and the ability to form a 1:2 complex with hGHBP. Truncation of 20 amino acids further decreased affinity toward both hGHBP and receptors in intact IM-9 lymphocytes and completely abolished formation of a 1:2 complex with hGHBP. Both des-13-bPLs and bPL-des-17 (L28F) retained their full ability to stimulate insulin-like growth factor-I secretion by rat hepatocytes compared to that of bPL. The insulin-like growth factor-I stimulatory activities of bPL-des-17 and bPL-des-20, however, were decreased to 1-5%. These results indicate that the stoichiometry of 1:2 complex formation with hGHBP may be preserved despite decreased receptor binding affinity, but the lower affinity of the putative site 1 or site 2 of the analog may account for the decrease in biological activity. Furthermore, the ability or inability of bPL or its truncated analogs to form 1:2 complexes with soluble hGHBP cannot predict their somatogen receptor-mediated biological activity in rat hepatocytes. PMID- 7867581 TI - Parathyroid hormone stimulates ecto-5'-nucleotidase activity in renal epithelial cells: role of protein kinase-C. AB - PTH-induced phosphaturia is exerted in part by cAMP added to the renal tubular lumen under the influence of the hormone. Modulation of renal phosphate transport by luminal cAMP requires degradation of the nucleotide into adenosine by brush border membrane ectoenzymes, among them ecto-5'-nucleotidase (5'-NU). Hormonal modulation of 5'-NU activity was evaluated in cultured opossum kidney cells. PTH (1-100 nM) stimulated 5'-NU in a time-, concentration-, and protein synthesis dependent manner. The effect of PTH-(1-34) was mimicked by PTH-(3-34), which does not activates adenylate cyclase, and by phorbol 12-myristate 13-acetate (PMA), but not by forskolin or (Bu)2cAMP. Down-regulation or pharmacological inhibition of protein kinase-C (PKC) abolished the effect of PTH fragments and PMA. PTH fragments increased intracellular Ca2+ and translocated PKC activity to the membrane. PTH or PMA did not affect 5'-NU messenger RNA content. Inhibition of sodium-phosphate cotransport by extracellular cAMP was decreased by 5'-NU inhibition and was magnified by PTH. These results indicate that 1) PTH stimulates 5'-NU activity in renal proximal tubular cells in a manner involving PKC activation and de novo protein synthesis; and 2) this effect participates in PTH modulation of renal phosphate transport. PMID- 7867582 TI - Stimulation of endosteal bone formation by systemic injections of recombinant basic fibroblast growth factor in rats. AB - In vivo effects of basic fibroblast growth factor (bFGF) on bone formation was examined in rats. Daily systemic injections of 100 micrograms/kg bFGF for 7 days caused a marked stimulation of endosteal bone formation in both cortical and secondary cancellous bone areas. Histological examinations revealed that the sequence of responses to the injections of bFGF consisted of three phases: an early increase in the number of preosteoblastic cells over the osteoblastic cell layer (days 1-3), recruitment of osteoblasts from preosteoblastic cells (days 3 5), and an increase in new bone formation (days 5-7). These histological changes in the endosteum correlated closely with histomorphometrical parameters of bone formation, and the endosteal mineral apposition rate was almost unaffected during the initial 4 days but was markedly enhanced after this period. Immunohistochemical examinations using antitransforming growth factor (TGF)-beta 1 antibody demonstrated that immunostaining of preosteoblastic cells for TGF-beta already increased 1 day after bFGF treatment. Distribution of TGF-beta in osteoblasts and bone matrices began to increase on day 3, and all the osteoblasts and new bone matrices were intensively immuno-stained on day 7. These results demonstrate that systemic injections of bFGF in rats stimulate endosteal bone formation, and that the stimulation of bone formation is preceded by an initial increase in preosteoblastic cells with later recruitment of osteoblasts from these cells. Because the distribution of TGF-beta in the endosteal cells is increased by bFGF, the effect of bFGF may at least in part be mediated by TGF beta. However, the precise mechanism of action of bFGF on bone formation remains to be clarified. PMID- 7867583 TI - Vasopressin stimulates steroid secretion in human adrenal glands: comparison with angiotensin-II effect. AB - Autoradiographic experiments using iodinated vasopressin analog revealed the presence of specific vasopressin-binding sites in the human adrenal cortex (zona glomerulosa and zona fasciculata). These receptors exhibited a good affinity for arginine vasopressin (3.3 nM), with classical V1a pharmacology and densities of 65 and 135 fmol/mg protein-enriched membranes from zona glomerulosa and fasciculata, respectively. Vasopressin receptors present in both glomerulosa and fasciculata cell-enriched primary cultures were coupled to phospholipase C (ED50, 0.9 and 1.8 nM; maximal stimulation, 4.3- and 5.8-fold, respectively). Vasopressin also stimulated an increase in intracellular calcium through at least two distinct mechanisms: the mobilization of intracellular pools via vasopressin stimulated inositol phosphate accumulation and the activation of calcium influx. In glomerulosa cell-enriched primary cultures, vasopressin increased aldosterone secretion (ED50, 0.4 nM; maximal stimulation, 2.5-fold) and was found to be as potent as angiotensin-II in stimulating aldosterone secretion, phosphoinositide turnover, and calcium mobilization. In fasciculata cells, vasopressin and angiotensin-II were also able to stimulate cortisol secretion and inositol phosphate accumulation. Moreover, perifusion experiments demonstrated that vasopressin was released from the adrenal medulla. Together, these results indicate that vasopressin can be considered a potent paracrine modulator of adrenal steroid secretion in man. PMID- 7867584 TI - Estradiol enhances the stimulatory effect of insulin-like growth factor-I (IGF-I) on mammary development and growth hormone-induced IGF-I messenger ribonucleic acid. AB - Pubertal mammary development in the rat is largely dependent upon GH and estrogen. We recently showed that insulin-like growth factor-I (IGF-I) can substitute for GH in inducing mammary development in male rats, suggesting that IGF-I mediates GH action. The present study investigated whether IGF-I, like GH, required estradiol (E2) to act or whether IGF-I could substitute for both GH and E2. The effects of IGF-I were tested in the presence and absence of E2. Elvax pellets containing IGF-I or des(1-3) IGF-I were implanted into right lumbar mammary glands of sexually immature, hypophysectomized, oophorectomized female rats, with control BSA-containing pellets in the contralateral glands. After 5 days, both lumbar mammary glands were removed and examined in whole mounts for mammary development by counting terminal end buds and alveolar structures. E2, administered in SILASTIC brand capsules, had no independent effect on mammary development. In the absence of E2, des(1-3) IGF-I had a small, but significant, independent effect on mammary development; native IGF-I was ineffective. The addition of E2 significantly enhanced the effects of IGF-I and des(1-3) IGF-I on mammary development, similar to that noted when E2 was given along with GH. We also studied the effects of E2 and/or hGH on mammary gland IGF-I messenger RNA (mRNA) in hypophysectomized castrated male animals. E2 alone did not increase mammary gland IGF-I mRNA concentrations, but E2 enhanced the effect of hGH on IGF I mRNA by 4- to 6-fold. These studies indicate that IGF-I can have a small independent effect on mammary development, but like GH, E2 is required for a full effect. They also indicate that E2 is capable of synergizing with GH in the production or expression of IGF-I mRNA, and that the action of E2 on mammary development may take place at multiple sites. If locally produced IGF-I does indeed mediate the action of GH in mammary development, then although E2 is capable of enhancing the effect of GH on IGF-I mRNA, its major effect in mammary development occurs after IGF-I is produced. PMID- 7867585 TI - The developmental pattern of androgen receptor expression in rat prostate lobes is altered after neonatal exposure to estrogen. AB - Brief administration of estrogen to newborn rats permanently imprints adult prostatic androgen receptor (AR) expression in a lobe-specific manner. To delineate this effect, we examined the immediate effects of early estrogen exposure on the changing AR pattern in the developing ventral, dorsal, and lateral prostate lobes. Antibodies against rat AR (PG-21) were used in combination with several antibodies to cell-specific antigens for positive cellular identification by immunocytochemistry. At birth, mesenchymal cells of the ventral prostate were strongly AR positive (AR+). Epithelial cells stained only for basal cell cytokeratins and, in contrast to earlier reports, many were AR+ on day 1. Between days 3-5, periductal mesenchymal cells differentiated into smooth muscle cells which retained strong AR+ staining, whereas interductal fibroblasts exhibited a decreased incidence of AR+ cells. Between days 5-10, luminal epithelial cells first appeared, and a striking increase in AR staining intensity was noted relative to that in the basal cells. During puberty, basal cells lost their AR immunoreactivity. Similar changes were observed in the dorsal and lateral lobes. Newborn rats were given 25 micrograms estradiol benzoate on days 1, 3, and 5 and were killed thereafter. By day 6, AR staining was markedly decreased to a weak to moderate intensity in all cell types, and by day 10, AR was virtually absent in the separate lobes. Growth and epithelial cytodifferentiation were significantly retarded. Between days 15-30, evidence of luminal cell cytodifferentiation was noted; however, this was frequently not associated with an increase in AR staining. In the ventral and dorsal lobes, a continuous peripheral layer of AR-negative basal cells surrounded the ducts in the central and proximal regions, and this was associated with a permanent inability of luminal epithelial cells to express AR. Epithelial and smooth muscle AR expression was observed only in the distal tips. In contrast, AR expression rapidly returned in all regions of the lateral lobes, except the proximal ducts. We conclude that 1) basal epithelial cells express AR as early as day 1 of life and should be considered as possible direct targets of androgen action during prostate morphogenesis; 2) differentiation into luminal cells is associated with an increase, rather than an induction, of AR expression; and 3) periductal smooth muscle cells retain strong AR expression throughout development and should be considered primary targets for androgen-mediated morphogenesis. Neonatal estrogen initially down-regulates AR expression in all cells of three lobes, which may explain the overall growth retardation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7867586 TI - Effects of tachykinins on the secretory activity of rat Sertoli cells in vitro. AB - In the present study we investigated the effects of various tachykinins on the secretory activity of rat Sertoli cells in vitro. Sertoli cells were isolated from testes of immature Sprague Dawley rats, cultured for 4 days and thereafter incubated with three concentrations (0.1 pM, 1 pM or 100 pM) of substance P (SP), neurokinin A (NKA), neuropeptide K (NPK) or neuropeptide gamma (NPG) for 24 h. Levels of transferrin and lactic acid were determined in the culture media and expressed per micrograms of cellular DNA. Among all the peptides studied, NPG exhibited the greatest stimulatory effect on the release of transferrin and lactate, with NKA and NPK being less potent and SP being the least potent. Also, the effects of tachykinins on the aromatase activity of cultured Sertoli cells, as reflected by their ability to metabolize testosterone to estradiol (E2), were studied. No stimulatory effect was observed at lower concentrations (1 pM), while at 100 pM both NPG and NKA increased estradiol levels in the medium. SP and NPK had no significant effect on estradiol levels in the medium. This study reveals that tachykinins are able to influence the secretory activity of Sertoli cells, and that some of these peptides can also enhance the aromatase activity. Thus there is a possibility that tachykinins may have a physiological role as modulators of the function of Sertoli cells. PMID- 7867587 TI - Differential involvement of protein kinase C in the regulation of transforming growth factor-beta (TGF-beta) secretion by porcine theca and granulosa cells in vitro. AB - Transforming growth factor-beta (TGF-beta) has been implicated in the regulation of ovarian follicle development. Little, however, is known regarding the regulation of TGF-beta expression within the follicle. To investigate this, granulosa and theca cells were isolated from small antral follicles of prepubertal porcine ovaries, maintained in monolayer culture, and treated with gonadotropins or intracellular activators of the protein kinase A and C pathways. TGF-beta secreted into the medium was measured using a proliferation inhibition bioassay with MvLu1 epithelial cells. Over a broad dose range, FSH and LH were ineffective in stimulating TGF-beta secretion relative to controls in granulosa and theca cells, respectively. Additionally, 8-bromo-cAMP, a direct activator of protein kinase A, was ineffective in stimulating TGF-beta secretion in either cell type. In marked contrast, PMA, a stimulator of protein kinase C, dose dependently stimulated TGF-beta secretion in theca cells. Interestingly, however, PMA had virtually no effect upon granulosa cells. The stimulatory effect of PMA on theca cell TGF-beta secretion was not observed with the inactive derivitive 4 alpha-PMA, and the PMA effect was inhibited by chelerythrine chloride, an inhibitor with high specificity toward protein kinase C. Taken together, these results argue against a direct role of the protein kinase A pathway in the regulation of TGF-beta expression in porcine follicle cells and support direct involvement of the protein kinase C pathway. Moreover, there appears to be marked differences in the regulation of this growth factor between theca and granulosa cells. PMID- 7867588 TI - Selective uptake of estrogenic compounds by Saccharomyces cerevisiae: a mechanism for antiestrogen resistance in yeast expressing the mammalian estrogen receptor. AB - Estrogen antagonists such as ICI164,384 do not inhibit 17 beta-estradiol (E2) dependent gene activity in yeast expressing the mammalian estrogen receptor although these compounds bind to receptors isolated from these cells. Various explanations have been offered for antiestrogen resistance in yeast systems including differences in cell-specific components and lack of permeability of the yeast cell wall to these compounds. We have used a strain of Saccharomyces cerevisiae transformed with the human estrogen receptor gene, and two estrogen response elements linked to a lacZ reporter gene to study the pharmacology of estrogen agonists and antagonists. The rank order of potency of estrogen agonists in this strain (CY525) is similar to that in estrogen-dependent mammalian cells: DES > or = E2 > E1 > E3 = zeranol. Competitive binding with 3H-E2 by these compounds in cell-free extracts of CY525 results in a similar order of potency with a reverse order for E1 and E3. The pure estrogen antagonist ICI164,384 also binds to the receptor from cell-free extracts of CY525 with an IC50 of approximately 14nM. As in mammalian cells ICI164,384 does not induce E2-dependent gene activity. However, unlike mammalian cells, E2-induced gene activity in CY525 is not inhibited by ICI164,384. Intact CY525 cells incubated with 3H-17 beta estradiol were found to specifically bind the labeled ligand since excess unlabeled E2 effectively competed for binding. Unlabeled DES and E1 were also found to compete, however, excess unlabeled ICI164,384, E3 and the second generation antagonist ICI182,720 were unable to displace 3H-E2 binding in intact cells. These results indicate that certain compounds enter the intact yeast cell more readily than others and offer an explanation for antagonist resistance in these organisms. PMID- 7867589 TI - When tamoxifen turns bad. PMID- 7867590 TI - Prolonged treatment of breast cancer cells with antiestrogens increases the activating protein-1-mediated response: involvement of the estrogen receptor. AB - At micromolar (pharmacological) concentrations, the action of tamoxifen on the proliferation of estrogen-dependent cells can be mediated not only by the estrogen receptor (ER), but also by other target molecules, such as protein kinase-C (PKC), which are easily inhibited by antiestrogens in cell-free experiments. By developing MTLN and MDT cell lines, in which any modulation of PKC activity is reflected by a variation of the expression of an activating protein-1 (AP-1)-controlled firefly luciferase gene, we investigated whether such antiestrogen inhibitory effects on PKC occurred in intact breast cancer cells. Firstly, in short term (4-h) treatment of both cell lines, antiestrogens only inhibited the 12-O-tetradecanoyl-phorbol-13-acetate-induced luciferase activity at very high concentrations (30 microM). A cytolytic effect was also observed. Secondly, in prolonged (4-day) treatments of MTLN (ER-positive) cells, low antiestrogen concentrations (nanomolar) decreased the basal AP-1 response by about 2 and increased the 12-O-tetradecanoyl-phorbol-13-acetate-stimulated AP-1 response by about 3-4. This stimulation was mediated by ER, because 1) dose response curves established with tamoxifen and hydroxytamoxifen were in agreement with their affinity for ER; 2) when present with antiestrogens, estradiol abolished this phenomenon; and 3) this effect was not observed in MDT (ER negative) cells. Such a latent activation of AP-1 pathway could appear in the course of breast cancer antiestrogen treatment, in conditions where natural PKC activators are abnormally produced with unexpected consequences on the results of a long term antiestrogen treatment. PMID- 7867591 TI - Transcriptional vs. posttranscriptional control of neuropeptide Y gene expression. AB - Human neuropeptide Y (NPY) gene expression occurs exclusively in the central and peripheral nervous systems requiring complex cell-specific regulation. In this study we have examined the effect of modulating the second messenger systems involving protein kinase A and protein kinase C on the expression of the NPY gene in different neuronal cell types. We report that the effects of 12-O tetradecanoyl phorbol-13-acetate (TPA) and forskolin on a neuroblastoma cell line (LA-N-5) and a pheochromocytoma cell line (PC12) are mediated through both increased transcription of the NPY gene and through stabilization of NPY messenger RNA (mRNA). After 8 h of treatment TPA and forskolin increase the steady-state level of NPY mRNA 10- and 12-fold in LA-N-5 and PC12 cells, respectively. This response in neuroblastoma cells is due to an increase in the half-life of NPY mRNA. The response in PC12 cells is mediated by both increased mRNA stability and increased transcription. Transient transfection analyses using PC12 cells indicate that only 51 base pairs 5' to the transcription start site are necessary for the TPA and forskolin induced transcriptional response. Thus, these experiments demonstrate that TPA and forskolin effect the regulation of the NPY gene via transcriptional and posttranscriptional mechanisms in a cell specific manner. PMID- 7867592 TI - Carboxyl-terminal peptides from parathyroid hormone-related protein stimulate osteoclast-like cell formation. AB - The role of the carboxyl (C)-terminal portion of PTH-related protein (PTHrP) in bone resorption continues to be controversial. The present study was performed to examine the effect of C-terminal PTHrP peptides on osteoclast-like cell formation as well as bone resorption in mice. C-Terminal PTHrP peptides [human (h) PTHrP (107-139) and hPTHrP-(107-111); 10(-10)-10(-8) M] stimulated osteoclast-like cell formation in a concentration-dependent manner in osteoblast-containing mouse bone cell cultures. Moreover, osteoclast-like cells newly formed by these peptides possessed the ability to form pits on the dentine slices. The conditioned medium from UMR-106 cells and MC3T3-E1 cells pretreated with the C-terminal peptides did not affect osteoclast-like cell formation from mouse hemopoietic blast cells derived from spleen cells. The C-terminal peptides as well as hPTHrP-(1-34) stimulated osteoclast-like cell formation from mouse hemopoietic blast cells in the absence of osteoblasts, although both amino- and C-terminal peptides were unable to support hemopoietic blast cells. Protein kinase-C inhibitors (H-7 and staurosporine) almost completely inhibited the stimulation of osteoclast-like cell formation by the C-terminal peptides in both the presence and absence of osteoblasts. The C-terminal peptides did not affect bone resorption by mature osteoclasts in osteoblast-containing mouse bone cell cultures. The present study indicates that C-terminal PTHrP peptides possess the ability to stimulate osteoclast-like cell formation in both the presence and absence of osteoblasts, possibly through the pathway involving protein kinase-C activation. PMID- 7867593 TI - Activin promotes ovarian follicle development in vitro. AB - Activin is a protein originally isolated from follicular fluid as a factor stimulating FSH release from the pituitary. The present experiments support the hypothesis that activins may also regulate follicle development by autocrine/paracrine mechanisms. Granulosa-oocyte complexes were isolated by collagenase/dispase dispersion of ovaries from 14- or 21-day-old rats and cultured in serum-free medium. Within 24 h, the cells had spread to form a monolayer. Hormones and growth factors were added at this time. Cell number and thymidine incorporation were measured after an additional 72 h. In the presence of insulin and transferrin, activin-A increased both granulosa cell number and thymidine incorporation more than 2-fold. This effect could be inhibited by follistatin, an activin-binding protein. In addition, activin-A, in the presence of FSH, induced reorganization of follicular structures from monolayer culture of cells from 14-day-old rats and caused cells from primary follicles to develop into large follicle-like structures. These structures contained oocytes, a cumulus layer, an antrum, and a multilayered follicular wall with a diameter of more than 1 mm. Electron microscopy revealed that the cells in the follicle-like structure were connected by gap junctions. Oocytes showed a mature morphology and had closely associated cumulus layers. Dissociation of the follicular wall in these follicle-like structures was induced by the addition of LH, resembling the induction of ovulation in vivo. The findings are important for understanding follicular development and atresia. PMID- 7867594 TI - Prevention of type I diabetes in NOD mice by nonhypercalcemic doses of a new structural analog of 1,25-dihydroxyvitamin D3, KH1060. AB - Pharmacological amounts of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] have potent immunoregulatory activity, but with marked effects on calcium and bone metabolism. In this study we demonstrate that nonhypercalcemia-inducing nondemineralizing doses of an analog of 1,25-(OH)2D3, 1 alpha,25-(OH)2-20-epi-22 oxa-24,26,27-trishomo-vitamin D (KH1060), can prevent type I diabetes. Female NOD mice received 1,25-(OH)2D3 (5 micrograms/kg), KH1060 (0.4 or 0.2 micrograms/kg), or the treatment vehicle ip every 2 days from 21-200 days of age. The incidence of diabetes in controls was 17 of 31 (55%), whereas 7 of 38 (18%) 1,25-(OH)2D3 treated mice, 3 of 27 (11%) KH1060 (0.4 micrograms/kg)-treated mice, and 6 of 27 (22%) KH1060 (0.2 micrograms/kg)-treated mice developed diabetes (P < 0.025 vs. controls). Protection was achieved with the low KH1060 dose without effects on calcium or bone metabolism, as evaluated by serum calcium (9.5 +/- 0.4 vs. 9.4 +/ 0.3 mg/dl in controls; P = NS), serum osteocalcin (82 +/- 17 vs. 83 +/- 20 ng/ml; P = NS), bone calcium content (6.8 +/- 0.7 vs. 6.4 +/- 0.5 mg/tibia; P = NS), urinary calcium (21 +/- 4 vs. 21 +/- 4 mg/dl; P = NS), pyridinoline excretion, and duodenal calbindin-D9K concentration. The proposed mechanism of action is a restoration of suppressor cell activity, as demonstrated in vitro (suppressor cell assay) and in vivo (cell transfer experiments). This study demonstrates that an analog of 1,25-(OH)2D3 prevents type I diabetes in NOD mice without significant effects on calcium or bone metabolism. PMID- 7867595 TI - Differential regulation of epidermal growth factor and transforming growth factor alpha messenger ribonucleic acid in the rat anterior pituitary and hypothalamus induced by stresses. AB - Evidence has shown that epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are present in the anterior pituitary as well as the hypothalamus, and that EGF can influence the function of pituitary cells, particularly corticotropes in vivo and in vitro. However, little is known about their exact functional roles and how they are regulated in these two areas. The present study was designed to determine if EGF and TGF alpha messenger RNA (mRNA) are expressed in the rat anterior pituitary and hypothalamus and how stress conditions such as cold, ether, or restraint affect their local expression. A sensitive mRNA detection method, the ribonuclease protection assay, detected both EGF and TGF alpha mRNA in the rat anterior pituitary and hypothalamus. Reverse transcription-polymerase chain reaction (RT-PCR) further showed the presence of EGF and TGF alpha mRNA in these two areas and several other rat tissues (submandibular gland, liver, kidney, lung cerebral cortex, and testis). No TGF alpha mRNA was found in the kidney, however. EGF mRNA was up-regulated in the anterior pituitary after 30 min acute cold stress (CS) and restrainer-restraint stress (RS) but not 30 min after ether stress (2 min, ES), novelty stress (NS), or tape-restraint stress (TS). Further analysis showed that EGF mRNA expression decreased after 1 h CS (1C) and then increased after 3 h CS (3C). In contrast, TGF alpha mRNA in the anterior pituitary and hypothalamus and hypothalamic EGF mRNA did not show significant changes in response to either acute stresses (CS, ES, RS, TS, NS) or longer CS (1C, 3C). Our results suggest that 1) EGF, is up regulated after some stresses; 2) increased pituitary EGF mRNA in response to stresses varies with the type of stress; and 3) pituitary TGF alpha and hypothalamic EGF and TGF alpha may be not involved in the stress response. PMID- 7867596 TI - Tumor necrosis factor-alpha and interferon-gamma modulate gene expression of type I 5'-deiodinase, thyroid peroxidase, and thyroglobulin in FRTL-5 rat thyroid cells. AB - Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) have many effects on a number of cell types, including thyrotrophs. In the present study, we used FRTL5 cells, a cultured rat thyroid follicular cell line, to examine the effects of IFN-gamma and TNF-alpha on type I 5'-deiodinase (5'D-I) activity and 5'D-I, thyroid peroxidase (TPO) and thyroglobulin (Tg) gene expression. Incubation of FRTL5 cells with the highest concentrations of TNF alpha and IFN-gamma tested (1000 ng/ml or 1000 U/ml, respectively) for 72 h in the presence and absence of TSH had no effect on cell viability as assessed by trypan blue exclusion. In TSH-deprived FRTL-5 cells, TNF-alpha and IFN-gamma resulted in a small but dose-dependent decrease in 5'D-I activity. TNF-alpha or IFN-gamma blocked the TSH- or cAMP-induced rise in 5'D-I activity. 100 ng/ml TNF alpha and 100 U/ml IFN-gamma completely blocked the TSH- or cAMP-induced rise in 5' D-I activity. However, when cells were incubated with TNF-alpha and IFN-gamma, in combination, there was a marked decrease in 5'D-I activity, with TNF-alpha (25 ng/ml) plus IFN-gamma (25 U/ml) completely blocking the TSH-induced rise in 5'D-I activity. Northern blot analyses were performed to examine the effect of TNF alpha and IFN-gamma on 5'D-I gene expression. TNF-alpha had little effect on 5'D I messenger RNA (mRNA) levels, while IFN-gamma resulted in a modest decrease in 5'D-I mRNA levels in TSH-deprived cells, and in TSH-stimulated FRTL-5 cells. However, when TNF-alpha and IFN-gamma were added in combination there was a marked decrease in 5'D-I gene expression with TNF-alpha (50 ng/ml) plus IFN-gamma (50 U/ml) decreasing 5'D-I mRNA levels by 89 percent in TSH-deprived cells. In TSH-stimulated cells incubated with 500 ng/ml TNF-alpha plus 500 U/ml IFN-gamma, 5'D-I mRNA levels were almost undetectable. We also examined the effect of IFN gamma and TNF-alpha on TPO and Tg gene expression. As observed with 5'D-I mRNA levels, there was a synergistic effect of IFN-gamma and TNF-alpha on the inhibition of basal and TSH-stimulated TPO and Tg gene expression. These findings indicate that TNF-alpha and IFN-gamma in combination have a marked inhibitory effect on thyroid function, which is consistent with a decrease in thyroid hormone synthesis and metabolism. PMID- 7867597 TI - Regulation of gonadotropin-releasing hormone gene expression in the rat during the luteinizing hormone surge. AB - In the present study we characterized GnRH gene expression in intact female rats across the estrous cycle and during a steroid-induced LH surge in ovariectomized (OVX) rats, using the quantitative ribonuclease protection assay. We measured cytoplasmic messenger RNA (mRNA) levels and nuclear primary transcript levels as an index of transcription. In Exp I, cycling rats were killed at 1100 or 1800 h on estrus, diestrus day 1, or diestrus day 2 (D2) or at 1100, 1500, 1800, or 2100 h on proestrus (P). In Exp II, proestrous rats were killed at the same time points or injected with pentobarbital (Pb) at the onset of the LH surge and killed on that day or the following day. In Exp III, a LH surge was induced in OVX rats treated with estradiol benzoate plus progesterone. Rats were killed at 1200, 1500, 1600, 1700, or 2100 h on the day of the surge. For all experiments, blood samples were collected and frozen for quantitation of LH by RIA. The preoptic area-anterior hypothalamus was dissected, and cytoplasmic and nuclear RNA were extracted and assayed separately by ribonuclease protection assay. In Exp I, cytoplasmic mRNA levels exhibited two significant peaks, one on D2 and another at 1500h on P. Primary transcript levels were significantly elevated only at 1500 h on P. In Exp II, proestrous rats and rats given Pb and killed the next day had a peak in cytoplasmic mRNA levels at 1500 h, which was blocked in rats given Pb and killed the same day. In Exp III with OVX rats, no significant changes in mRNA or primary transcript levels were observed between steroid or control groups. We hypothesize that the increase in cytoplasmic mRNA levels in cycling rats on D2 is probably due to a posttranscriptional mechanism, because it was not paralleled by changes in primary transcript levels, which would be expected if a transcriptional mechanism were involved. On P, both cytoplasmic mRNA and primary transcript levels changed, suggesting a transcriptional mechanism at this time. PMID- 7867598 TI - Central endotoxin induces different patterns of interleukin (IL)-1 beta and IL-6 messenger ribonucleic acid expression and IL-6 secretion in the brain and periphery. AB - Centrally injected endotoxin induced high levels of interleukin (IL)-6 in serum, but the mechanisms of this induction and the signal conveying the information from the brain to the periphery are not yet known. To help characterize the pathway of centrally mediated induction of IL-6 in periphery, the cytokine levels were measured in rat serum and cerebrospinal fluid at different times after intracerebro-ventricular endotoxin (LPS, 2.5 micrograms/rat). In the same experiments, IL-6 and IL-1 beta messenger RNA (mRNA) expression, measured by Northern blot analysis, were evaluated in the periphery (adrenals, lymph nodes, and mononuclear cells) and brain (hypothalamus, hippocampus and striatum). In serum, IL-6 levels were highest after 2h; then they rapidly decreased. IL-6 mRNA showed the same time-course in adrenals and lymph nodes. The pattern in the central nervous system was different: in the cerebrospinal fluid, IL-6 was detectable starting from 2h, reaching a plateaux at 4-8h and remaining detectable until 16 h. IL-6 mRNA expression in the brain areas showed a similar time-course, reaching a maximum at 4-8 h. IL-1 beta mRNA induction started at the same time in brain and periphery, i.e. 1 h after LPS, but the maximal effect was reached at 2 h in mononuclear cells, adrenals, and lymph nodes, and at 8 h in brain regions. The results indicate that circulating IL-6 induced by central LPS is produced mainly peripherally and that synthesis of IL-6 and IL-1 beta are regulated differently in the brain and periphery. PMID- 7867599 TI - Endogenous glutamate involvement in pulsatile secretion of gonadotropin-releasing hormone: evidence from effect of glutamine and developmental changes. AB - The secretion of GnRH can be stimulated by glutamate (GLU) and GLU agonists, whereas GLU receptor antagonists inhibit GnRH. Using 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of glutaminase, we aimed to study the involvement of endogenous GLU in GnRH secretion through the effects of impaired GLU biosynthesis from its precursor glutamine (GLN). GnRH secretion by hypothalamic explants of male rats, aged 15 and 50 days, was compared, because the frequency of spontaneous GnRH secretory pulses showed a 2-fold increase between those two ages. Using explants of 50-day-old rats, GLN elicited GnRH secretion in a similar dose-related manner as GLU. DON prevented GLN-evoked secretion of GnRH, whereas the effect of GLU was not altered. DON also markedly inhibited spontaneous pulsatile secretion of GnRH and the secretory response to veratridine, a Na+ channel opener. The inhibitory effect of DON on veratridine-evoked secretion of GnRH was directly related to the duration of exposure to DON and the frequency of GnRH secretory episodes. Using explants of 15-day-old rats, GLN could elicit GnRH release, although this response was lower than GLU-evoked secretion of GnRH. The DON concentrations required for inhibition of veratridine-evoked secretion of GnRH were lower at 15 days than at 50 days. These data indicate that 1) GLU biosynthesis from GLN is a prerequisite to the physiological mechanism of pulsatile GnRH secretion; and 2) inhibition of veratridine- or GLN-induced secretion of GnRH requires higher DON concentrations after the onset of puberty than before. This suggests that glutaminase, the enzyme controlling GLU biosynthesis from GLN, shows increased activity after the onset of puberty when the frequency of pulsatile GnRH secretion is increased as well. PMID- 7867600 TI - Expression and functionality of luteinizing hormone/chorionic gonadotropin receptor in the rat prostate. AB - In addition to androgens that are essential for maintenance of prostate growth and function, nonandrogenic hormones must also be considered to explain some regulatory events occurring in the prostate. The detection of LH/CG receptor (LH/CG-R) gene expression in some nongonadal tissues, has led us to consider LH as a potential regulatory factor of prostatic development and function. In this study, we have demonstrated by RT-nested polymerase chain reaction and Northern blotting that the rat prostate contains the same LH/CG-R transcript as the gonads. Western immunoblotting, ligand blotting, and binding analysis have shown that rat prostate also contains a 93-kDa receptor protein that is able to bind [125I]hCG specifically and with a high affinity (6.0 x 10(9) M-1). Our results also indicated that the concentration of binding sites was lower in the prostate than in the gonads. LH/CG-R sites of expression have been localized in the prostate by immunohistochemistry: specific staining was observed in all the epithelial cells of the gland, but the ventral lobes are much more immunoreactive than the lateral and dorsal lobes. Finally, the ability of this prostatic LH/CG-R to induce a physiological response was evaluated in an explant culture system. A time course experiment was carried out, and we observed a significant dose dependent stimulation of cAMP production after 3 h of treatment: 3.0 +/- 0.4, 4.2 +/- 0.4, and 5.0 +/- 0.5 pmol/ml of cAMP for 0, 100, and 500 ng/ml of LH, respectively. In conclusion, LH is able to act directly on the prostatic gland through specific receptors that are structurally and functionally very similar to those expressed in the gonads and are mainly localized in the ventral lobe of the organ. These data suggest that LH plays a significant physiological role in the prostate. PMID- 7867601 TI - Cocaine-sensitive sigma-receptor and its interaction with steroid hormones in the human placental syncytiotrophoblast and in choriocarcinoma cells. AB - The expression and ligand binding characteristics of sigma-receptors in human placental syncytiotrophoblast and choriocarcinoma cells were investigated using haloperidol as a ligand. Haloperidol bound to purified placental brush border membranes with high affinity; the apparent dissociation constant for the process was about 3 nM. These binding sites were not related to dopamine (D2) and serotonin (5-HT2) receptors nor to serotonin and norepinephrine transporters. The ligands of sigma-receptors [3.g. (+)-3-(3-hydroxyphenyl)N-(1-propyl)piperidine, 1,3-di-(2-tolyl)guanidine, clorgyline, rimcazole, and dexromethorphan] were very potent in competing with haloperidol for the binding sites. The binding sites were detected not only in the brush border membrane, but also in intracellular membranes. The rank order of potency of various sigma-receptor ligands to inhibit haloperidol binding indicated that placental sigma-receptors belong to the sigma 1 subtype. Cocaine and its analog RTI-55 [2 beta-carbomethoxy-3 beta-(4 iodophenyl-) tropane] inhibited the binding of haloperidol to placental membranes with appreciable potency. The steroid hormones, progesterone and testosterone, were also potent inhibitors, and the inhibition constant for progesterone was 0.3 microM, a concentration much smaller than that found in plasma during pregnancy. The inhibition was competitive. beta-Estradiol and a number of other steroids were relatively much weaker inhibitors than progesterone and testosterone. Phenytoin and neuropeptide-Y did not interact with sigma-receptors in placenta. The choriocarcinoma cell line JAR was also found to express sigma-receptors in the plasma membrane as well as in intracellular membranes. The characteristics of the receptors in this cell were qualitatively similar to those of the receptors in normal placenta, including subtype identity and interaction with cocaine and progesterone. Interestingly, however, all sigma-receptor ligands interacted with the receptors in the JAR cell with much higher affinity than with the receptors in normal placenta. It is concluded that the placental syncytiotrophoblast and choriocarcinoma cells express cocaine-sensitive sigma-receptors and that progesterone is most likely an endogenous ligand for these receptors. PMID- 7867602 TI - Retinoic acid and thyroid hormone regulate placental lactogen expression in human trophoblast cells. AB - In this study, we have demonstrated that retinoic acid (RA) and thyroid hormone (T3) stimulate the synthesis and release of human placental lactogen (hPL), one of the major secretory products of syncytiotrophoblast cells. Enzymatically, dispersed trophoblast cells from term placentas exposed continuously to RA (0.5 microM) and T3 (0.1 microM) for 5 days released significantly more hPL than control cells after 3 days of exposure (P < 0.001 in each instance). On days 4 and 5, the amounts of hPL released by cells exposed to RA and T3 were approximately 3- and 5-fold higher than those in control cells, respectively. The stimulation by both RA and T3 was dose dependent and was accompanied by stimulation of hPL messenger RNA levels. RA and T3 caused 3.5- and 5.6-fold increases, respectively, in chloramphenicol acetyltransferase activity in BeWo choriocarcinoma cells transfected transiently with a 2.3-kilobase (kb) fragment of the hPL promoter (-2300 to 2 basepairs) coupled to a chloramphenicol acetyltransferase reporter gene. Deletion construct analysis of the hPL promoter (2.3, 1.2, and 0.5 kb) indicated that the T3- and RA-responsive elements are localized -0.5 to -1.2 kb up-stream from the transcriptional start site (+1), where several consensus RA- and T3-responsive element sites are present. These results indicate that RA and T3 stimulate the synthesis and release of hPL by a mechanism involving hPL gene transcription and further support a role for these steroids in placental function. PMID- 7867603 TI - Induction of classical lactotropes by epidermal growth factor in rat pituitary cell cultures. AB - Long term incubation of pituitary tumor GH3 cultures with epidermal growth factor (EGF) induces reciprocal changes in PRL and GH production. However, it is not known whether EGF alters the cellular composition of these cultures. Another unanswered question is whether chronic treatment with EGF stimulates PRL secretion from nonneoplastic pituitary cells. In this study, GH3 cells and pituitary cells from neonatal (10-day-old) rats were cultured for 6 and 2 days, respectively, in the absence or presence of 5 nM EGF. Cells containing PRL and/or GH were then enumerated using light microscopic immunocytochemistry. In addition, neonatal pituitary cells were subjected to reverse hemolytic plaque assays for PRL. EGF treatment drastically increased the proportion of classical lactotropes (cells that secrete only PRL) in the GH3 cultures, from about 0.5% to 8% of all cells, without modifying the percentage of GH-positive cells. A similar action of EGF was observed in the primary cultures. Moreover, EGF enhanced by 240% the amount of PRL secreted from the neonatal lactotrope population during 1-h incubations under basal conditions. This effect was mediated by a selective increase in the relative number of PRL secretors forming large plaques. The results suggest that EGF promotes the differentiation of classical lactotropes in both GH3 cultures and pituitary cultures from neonatal rats, and that these cells are characterized by a high basal rate of PRL secretion. PMID- 7867604 TI - Characterization and regulation of two testicular inhibin/activin beta B-subunit messenger ribonucleic acids that are transcribed from alternate initiation sites. AB - We and others have shown that the inhibin/activin beta B-subunit gene is expressed differently in the gonads. Two species of 4.8- and 3.7-kilobase (kb) beta B-subunit messenger RNA (mRNA) with equal concentrations were identified in the testis, whereas 1 predominant 4.8-kb and a minor 3.7-kb mRNA were observed in the ovary. In this study, we analyzed the structures of these 2 mRNAs in rat testis and showed that both 4.8- and 3.7-kb beta B-subunit mRNAs were terminated at the region proximal to 2.2 kb down-stream from the translation stop codon. However, only 4.8-kb mRNA could be detected when RNA probes prepared from the 5' region 1 kb up-stream from the translation start site were used for Northern blot analysis. Our observations suggested that the 2 heterogeneously sized beta B subunit mRNAs are transcribed from different initiation sites. Transcription of the 4.8-kb mRNA was initiated at 3 adjacent nucleotides, GGA, 1.1 kb up-stream from the translation start codon ATG, whereas multiple transcription initiation sites spreading over 150 nucleotides upstream from the ATG codon were previously identified for 3.7-kb mRNA. Neither of the 2 transcripts contained TATA and CAAT boxes in their promoters. The 5'-flanking DNAs required for transcription of the 4.8- and 3.7-kb mRNA were examined by their ability to induce transient expression of the chloramphenicol acetyltransferase (CAT) gene in MA-10 Leydig tumor cells. A marked increase in CAT activity was detected when the 5'-flanking DNA for the 4.8- or 3.7-kb transcript was progressively shortened from its 5' end. Maximal CAT activity was observed when -409 and -139 basepair beta B-subunit DNA up-stream from the 4.8- and 3.7-kb transcription initiation site, respectively, were fused to the CAT gene, suggesting the presence of a negative regulatory element(s) at the up-stream regions of these promoters. Although putative AP-2 sites were identified, treatment of the transfected cells with cAMP and/or phorbol 12-myristate 13-acetate did not apparently change CAT activity driven by either the 4.8- or 3.7-kb promoter. Our results concluded that 1) the two inhibin/activin beta B-subunit mRNAs were transcribed from different initiation sites; 2) both promoters may be controlled by up-stream negative regulatory elements; and 3) neither of these promoters is responsive to cAMP and/or phorbol esters under the conditions employed. PMID- 7867605 TI - Hormonal regulation of mitogen-activated protein kinase activity in bovine adrenocortical cells: cross-talk between phosphoinositides, adenosine 3',5' monophosphate, and tyrosine kinase receptor pathways. AB - Angiotensin-II (AII), which stimulates steroidogenesis in bovine adrenocortical (BAC) cells through the phosphoinositides pathway, activates p42-p44 mitogen activated protein kinases (MAPKs) after 5 min of treatment (EC50 = 0.1 nM). This activation is 1) completely inhibited by the AII receptor AT1 subtype antagonist Dup 753 (10 microM), but unaffected by the AT2 antagonist PD 123177; 2) not reproduced by the AT2 agonist CGP 42112A; 3) insensitive to pretreatment with pertussis toxin; and 4) abolished by a 48-h preexposure of the cells to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA; 1 microM), which down regulates protein kinase-C activity. Fibroblast growth factor-2, a potent mitogen for BAC cells, which acts through its tyrosine kinase receptor, also activates MAPK (EC50 = 0.3 in a TPA-insensitive manner, while exhibiting no detectable effect on BAC cell steroidogenesis. In contrast, ACTH, which stimulates steroidogenesis via cAMP and inhibits BAC cell proliferation, does not stimulate MAPK. Indeed, ACTH completely blocks (IC50 = 0.01 nM) the stimulation of MAPK by AII, fibroblast growth factor-2, or TPA. Therefore, bovine adrenocortical cells provide an example of positive and negative hormonal regulation of MAPK activity through a cross-talk between the inositide-, cAMP-, and growth factor-activated tyrosine kinase pathways. PMID- 7867606 TI - Tonic modulation of dog thyrocyte H2O2 generation and I- uptake by thyrotropin through the cyclic adenosine 3',5'-monophosphate cascade. AB - The dog thyrocyte I- trapping activity and the expression of the genes coding for dog thyrocyte thyroglobulin or thyroid peroxidase are enhanced by TSH through the cAMP cascade and reduced by mitogens such as epidermal growth factor (EGF) or 12 O-tetradecanoylphorbol 13-acetate (TPA). In this work, we investigated whether H2O2 generation (a limiting step of thyroid hormone synthesis) is modulated by chronic treatment of the thyrocyte with TSH or mitogens such as EGF or TPA. We observed that both basal and carbachol- or ionomycin-stimulated H2O2 generation by the dog thyrocyte were concentration and time dependently enhanced by prolonged (12- to 72-h) exposure to TSH. This effect was reproduced by agents that increase the dog thyrocyte cAMP level or that mimic this increase. It was abolished when protein or RNA synthesis was inhibited. By contrast, EGF and TPA concentration and time dependently antagonized the effect of TSH. In addition, chronic exposure to EGF reduced both basal and carbachol- or ionomycin-stimulated H2O2 generation. The effect of TPA was reproduced by another protein kinase-C activating phorbol ester, phorbol dibutyrate, but not by beta-phorbol, an inactive phorbol ester. Modulation of dog thyrocyte H2O2 generation by chronic exposure to TSH or to the mitogens EGF and TPA was totally parallel to the modulation of their 125I- uptake. Taken together our results suggest that H2O2 generation (or at least one of its constituents) is a differentiation characteristic of the dog thyrocyte under tonic control of TSH through the cAMP cascade as iodide transport, thyroid peroxidase, and thyroglobulin. PMID- 7867607 TI - Homologous and heterologous regulation of gonadotropin-releasing hormone receptor gene expression in preovulatory rat granulosa cells. AB - The reverse transcription-polymerase chain reaction was used to evaluate the influence of gonadotropins and GnRH on GnRH receptor gene expression in cultured preovulatory rat granulosa cells. Cells were obtained from immature female rats 48 h after priming with 10 IU PMSG, sc, and cultured in medium containing LH, FSH, or GnRH after a 24-h preincubation period. After culture, cells were lysed, total RNA was extracted, and culture medium was assayed for its content of progesterone, and estradiol by RIA. Subsequent to reverse transcription, complementary DNA was subjected to polymerase chain reaction, after which the products formed were transferred to nylon filters and hybridized with a 416 basepair internal rat GnRH receptor complementary DNA probe. As an amplification control, Southern hybridization of glyceraldehyde-3-phosphate dehydrogenase messenger RNA (mRNA) was performed. Treatment with LH increased both progesterone and estradiol output, whereas GnRH receptor mRNA levels were markedly suppressed in a dose-related fashion, with maximal inhibition seen at 100-1000 ng (P < 0.05). In contrast, FSH in concentrations between 1-1000 ng was without effect on GnRH receptor gene expression. Time-course analysis revealed that GnRH receptor gene expression was not affected by LH (1000 ng) until 12 h, when transcript levels fell to 24% of those seen at 0 h (P < 0.05). This pronounced decrease in GnRH receptor mRNA abundance is, however, transient, because after 48 h, levels returned to those seen before LH treatment. As GnRH has been postulated to directly influence its own receptor synthesis in the pituitary, the effect of GnRH treatment of granulosa cells during a 24-h culture period was also evaluated. In GnRH-treated cells, a dose-dependent increase in GnRH receptor mRNA levels was seen, with maximal effects (2.4-fold; P < 0.05) at 10(-6) M. The demonstration of agonist-specific up- and down-regulation of GnRH receptor gene expression in preovulatory granulosa cells adds further support to the extrapituitary actions of GnRH as an important autocrine/paracrine factor involved in the regulatory events during the periovulatory period. PMID- 7867608 TI - Expression of messenger ribonucleic acid encoding cytochrome P450 side-chain cleavage, cytochrome p450 17 alpha-hydroxylase, and cytochrome P450 aromatase in bovine follicles during the first follicular wave. AB - The objective of the present study was to investigate changes in the expression of messenger RNAs (mRNAs) encoding cytochrome P450 side-chain cleavage (P450scc), cytochrome P450 17 alpha-hydroxylase (P450c17), and cytochrome P450 aromatase (P450arom) at different stages of the first follicular wave of the bovine estrous cycle. Groups of heifers (three to five per group) were ovariectomized on the day of initiation of the first follicular wave (as determined by ultrasonography, day 0) or on days 2, 4, 6, 8, and 10 after initiation of the first follicular wave following estrus. Expression of mRNAs encoding P450scc, P450c17, and P450arom was detected by in situ hybridization and quantified by image analysis. P450scc mRNA was localized to theca interna cells of large preantral follicles and also to granulosa cells of follicles 4 mm or greater in diameter. mRNA for P450c17 was localized exclusively to theca interna cells, whereas P450arom mRNA was localized to granulosa cells of follicles 4 mm or greater in diameter. There were changes in mRNA levels for all three enzymes in thecal and/or granulosa cells at different times of the first follicular wave. Before identification of the dominant follicle (i.e. on days 0 and 2), there was no change in expression of P450scc and P450c17 mRNAs, whereas expression of P450arom mRNA was higher on day 2 than on day 0. Maximal mRNA levels for all three enzymes were observed on day 4. By day 6, P450scc and P450c17 mRNA levels were reduced compared to those on day 4, whereas P450arom mRNA levels remained elevated. On day 8, mRNA levels for all three enzymes were reduced. After initiation of the second follicular wave (day 10), dominant follicles from the first wave were at an advanced stage of atresia. P450scc and P450arom mRNAs were undetectable in granulosa cells, and very low levels of P450scc and P450c17 mRNAs were observed in theca interna cells. Before identification of the dominant follicle, mRNA levels for all three enzymes were similar within a cohort of follicles. Therefore, expression of these enzymes may not be associated with the mechanism of selection of the dominant follicle during a follicular wave. PMID- 7867609 TI - Long term exposure to dopamine reverses the inhibitory effect of endothelin-1 on prolactin secretion. AB - This study was undertaken to assess the possibility that endothelin-1 (ET-1) and dopamine (DA) can act in concert to modulate PRL secretion. Enzymatically dispersed anterior pituitary cells obtained from random cycling female rats were perifused with Dulbecco's Modified Eagle's Medium supplemented with 0.2% BSA and 100 microM ascorbic acid. In the absence of dopamine, ET-1 (applied at 20 nM for 60 min) rapidly evoked a small transient elevation of PRL release, followed by a sustained inhibitory phase. Overnight perfusion with 500 nM DA-supplemented medium did not change the basic character of ET-1's effects on PRL secretion. Continuation of DA exposure for 48 h dramatically shifted the responsiveness of the lactotrophs to ET-1; the fast stimulatory response was robustly enhanced, whereas the inhibitory phase was replaced by a modest secondary elevation of basal PRL secretion. The stimulatory effect of ET-1 on PRL secretion after DA pretreatment was blocked by an ETA receptor antagonist, BQ-123. The effect of DA can be mimicked completely by a specific D2 receptor agonist (+/-)-2-(N-phenyl-N propyl)amino-5-hydroxytetraline hydrochloride, whereas pretreatment with a D1 agonist, SKF-39393, failed to change the responsiveness of lactotrophs to ET-1. Our data indicate that persistent activation of D2 receptors, a condition most closely resembling the in vivo environment of the lactotrophs, uncouples the inhibitory signaling pathway from the ETA receptor while synergistically affecting signal transduction, which mediates the ET-induced stimulation of PRL secretion. PMID- 7867610 TI - High level overexpression of glucose transporter-4 driven by an adipose-specific promoter is maintained in transgenic mice on a high fat diet, but does not prevent impaired glucose tolerance. AB - High fat feeding is associated with impaired insulin action, an obese body composition, and down-regulation of glucose transporter-4 (GLUT4) expression in adipocytes. We recently showed that overexpression of GLUT4 selectively in adipocytes of transgenic mice using the aP2 (fatty acid-binding protein) promoter/enhancer results in enhanced glucose tolerance and adipocyte hyperplasia. Here, we fed these GLUT4-overexpressing transgenic mice a high fat (55%) or a low fat (10%) diet for 13-15 weeks to determine the role of alterations in GLUT4 expression in adipocytes in the development of insulin resistance and obesity, which are characteristic of high fat consumption. In nontransgenic mice, high fat feeding results in 45-50% reduction of GLUT4 levels in white and brown adipose tissue, with a parallel decrease in insulin-stimulated glucose transport. In transgenic mice receiving the low fat diet, GLUT4 is overexpressed 20-fold in white and 4-fold in brown adipose tissue. Glucose transport in epididymal adipocytes is increased 20-fold in the basal state and 6 fold in the insulin-stimulated state. Even after transgenic mice are fed a high fat diet, GLUT4 expression and glucose transport in their adipocytes remains 14- to 30-fold greater than that in nontransgenic mice receiving the same diet. Despite these marked effects at the adipose cell level, glucose tolerance is not improved, probably due to insulin resistance in skeletal muscle and liver, where the transgene is not expressed. During the low fat diet, transgenic mice have 80% more body lipid than nontransgenics. High fat feeding increases body lipid 76% and adipocyte size 65% in nontransgenic mice, but has no effect in transgenic mice. Thus, overexpression of GLUT4 selectively in adipocytes protects against a further increase in adiposity. Furthermore, by using a heterologous promoter, high level overexpression of GLUT4 can be maintained even under metabolic conditions where it is normally down-regulated in adipocytes. This overexpression results in markedly increased glucose transport at the cellular level, but adipose-specific GLUT4 overexpression does not prevent the decrease in glucose tolerance associated with high fat feeding. PMID- 7867611 TI - Testing of sealing ability of endodontic filling materials. AB - Incomplete obturation of the root canal system is the major cause of endodontic failure. Endodontic filling materials with ability to seal the root canal are, therefore, essential for successful endodontic therapy. However, assessment of sealing ability is not included in the requirements specified in the current international standard covering root canal sealers. A number of different in vitro methods have been used to evaluate the sealing quality of endodontic filling materials. The tests have usually been leakage tests, i.e. based on assessment of penetration of a tracer along the obturated root canal. Leakage tests have poor reproducibility and are, therefore, not suited for standardized test programs. By selecting the properties necessary for sealing ability and testing them separately, it might be possible to find a number of tests, which individually are suitable for a standardized test program, and which combined will give information on the sealing ability of the test material. PMID- 7867612 TI - Effects of cooling and heating of the tooth on pulpal blood flow in man. AB - Laser Doppler flowmetry (LDF) was used to study the changes in pulpal blood flow (PBF) evoked by application of cold or heat to the palatinal surfaces of teeth 11 or 21 in nine young subjects. Switching from a thermode temperature of 33 degrees C to 5 degrees C on average induced a slow decrease of PBF to about 80% of control, and also warming to 39 degrees C evoked a small reduction in most subjects. Interindividual differences were large, however, and both cooling and warming sometimes triggered a rise in PBF. In contrast, skin blood flow, as recorded with LDF in the forearm, invariably rose during warming and fell during local cooling. The results suggested a more complex interaction between local and nervously mediated effects of moderate changes in temperature in the tooth pulp than skin, and that the previously held view of cold and heat decreasing and increasing PBF, respectively, is wrong. PMID- 7867613 TI - Relationship between file size and stiffness of stainless steel instruments. AB - The purpose of this study was to evaluate the relationship existing between file size and stiffness for three endodontic files of different cross-sections. Three groups of instruments were tested: Flexofiles from the Maillefer company, K Files and K-Flex from the Kerr company. Flexofiles have a triangular cross-section, K Files a square cross-section, and K-Flex instruments a rhombus cross-section from size 15 to size 40. For each group, 10 files from size 15 to size 40 were compared according to ANSI/ADA specification N degrees 28 for bending moment evaluation. There was a statistical difference between the three groups: the square cross-section K files presented a larger bending moment than the rhombus cross-section K Flex, which presented a higher bending moment than the triangular cross-section Flexofiles. There was an exponential relationship between file size and bending moment. PMID- 7867614 TI - An in vitro investigation into the cutting ability of ultrasonic K files. AB - Endosonic files vary in their oscillation when operated in air with the greatest displacement at the unconstrained tip. It was the aim of this study to investigate how files of different lengths and sizes varied in their ability to cut dentine. Single rooted teeth were sectioned to produce 1 mm dentine discs. These were positioned on a plastic block connected to a load transducer. Endosonic K-files (#15 to 25) were used to cut the disc for 10 s using operator assisted movement. The files contacted the disc at the following points along their length; apical (3 mm from tip), middle (8 mm from tip) and coronal (13 mm from tip) under applied loads of 30 and 50 g. The depth of cut produced by each file was measured using light microscopy. The #15 and #25 were similar in their pattern of dentine removal. The #20 file produced a large variation in its cutting ability and was also susceptible to fracture. The tip of the files was prone to constraint at higher loading with the thicker part of the file producing more cutting. It was concluded that the pattern of dentine removal of endosonic files was affected by the amount of load applied. The displacement amplitudes of endosonic files in air would not appear to be a good indicator of file cutting ability. PMID- 7867615 TI - Timing of calcium hydroxide therapy in the treatment of root resorption in replanted teeth in dogs. AB - The effect of time of the onset of calcium hydroxide (CH) pulpectomy on root resorption of 31 permanent dog incisors was investigated. CH pulpectomy was delayed 4, 9, 14 and 18 days after the teeth were extracted and replanted. Control teeth were replanted 1) without pulpectomy, 2) with a pulpectomy only or 3) with a pulpectomy and CH filling. All teeth were prepared for histologic evaluation 8 weeks after the teeth were replanted. Cross section were examined using a computer microscope and linear (micron) and/or square areas (micron 2) of surface (SRR), inflammatory (IRR), and replacement (RRR) root resorption were calculated. From this data the percentage of linear and area resorption was averaged for each group. Duncan multiple range t-test (P < or = 0.05) revealed that teeth in which a pulpectomy with CH filling was done extraorally had significantly greater SRR than the rest of the groups; teeth in which a pulpectomy without CH filling was done extraorally had significantly greater RRR than teeth in which CH pulpectomy was delayed for 18 days; there was no significant difference in SRR, IRR or RRR when CH placement was delayed 4, 9, 14 or 18 days after replantation. Although it was not significant the overall resorption was least when CH pulpectomy was delayed 18 days. PMID- 7867616 TI - A radiographic study of the effect of various retrograde fillings on periapical healing after replantation. AB - An effective retrograde sealing procedure places great demands upon both technique and materials. Prevention of micro-leakage, biocompatibility and stability of the material in the apical tissues are very important. To evaluate potential retrograde filling materials, a replantation model has been developed in which extracted permanent molars were replanted in monkeys after apicectomy of each root, preparation of a 2-mm deep retrograde cavity and its sealing with various dental materials. Prior to retro-filling the remaining pulp was exposed to saliva. Apicected molars which were infected and did not receive retrograde fillings served as positive controls. Periapical healing was evaluated radiographically after 8 weeks based on planimetric measurements of the size of the periapical radiolucency. The following dental materials were tested: amalgam, glass ionomer cement, calcium-hydroxide lining cement, AH 26 root canal sealer, various zinc oxide-eugenol cements, Cavit, and gutta-percha with various sealers. The materials which were associated with better apical healing than the infected controls were glass ionomer cement, Cavit, and the zinc oxide-eugenol cements. When plain zinc oxide-eugenol or IRM were combined with a gutta-percha core, healing was best and not statistically different from normal apices. It was concluded that radiographic assessment at 8 weeks of molar teeth retrograde filled prior to replantation could be a valuable method for discrimination of potentially useful materials in vivo. PMID- 7867617 TI - Replantation of avulsed permanent teeth with avital periodontal ligaments: case report. AB - Five maxillary anterior teeth lost during a grand mal epileptic seizure, were replanted using the technique recently described by Andreasen (1), after an extra alveolar period of more than 72 h. The teeth were replanted surgically, 10 days after being avulsed, after they had been immersed in a 2.4% sodium fluoride solution and root filled with gutta-percha. Ankylosis was evident 3 months post operatively. After 24 months there was evidence of considerable replacement resorption on the lateral incisors with little evidence of resorption on the other replanted teeth. Even though the long term prognosis is uncertain, this technique has an advantage of seeing the patient through the period of growth as well as maintaining the height of alveolar bone making possible the provision of an aesthetically acceptable prosthesis at a later age. PMID- 7867618 TI - Maxillary molar root fracture caused by sinus surgery: case report. AB - A case is presented in which a horizontal root fracture of the mesiobuccal root of a maxillary first molar was diagnosed as the source of a patient's chronic pain. Horizontal root fractures are rare in posterior teeth. The source of the fracture was determined to be trauma from access or curettage during two Caldwell Luc sinus procedures. A detailed history and endodontic retreatment led to the diagnosis. A mesiobuccal root resection resolved the chronic pain. PMID- 7867619 TI - Does mitogen-activated-protein kinase have a role in insulin action? The cases for and against. AB - The discovery of the mitogen-activated protein (MAP) kinase family of protein kinases has sparked off an intensive effort to elucidate their role in the regulation of many cellular processes. These protein kinases were originally identified based on their rapid activation by insulin. In this review we concentrate on examining the evidence for and against a role for the MAP kinases Erk-1 and Erk-2 in mediating the effects of insulin. While there is good evidence in favour of a direct role for MAP kinase in the growth-promoting effects of insulin and the regulation of Glut-1 and c-fos expression, and AP-1 transcriptional complex activity, this is by no means conclusive. MAP kinase may also play a role in the control of mRNA translation by insulin. On the other hand, the evidence suggests that MAP kinase is not sufficient for the acute regulation of glucose transport (Glut-4 translocation), glycogen synthesis, acetyl-CoA carboxylase or pyruvate dehydrogenase activity. The findings suggest that insulin may utilise at least three distinct signalling pathways which do not involve MAP kinase. PMID- 7867621 TI - The muscle-specific phosphoglycerate mutase gene is specifically expressed in testis during spermatogenesis. AB - Spermatogenesis is a dramatic differentiation process which involves very selective but poorly characterized gene-expression patterns. To gain insight into this process, we have investigated the expression during spermatogenesis of the genes that encode phosphoglycerate mutase, an essential glycolytic enzyme for the spermatozoa energy supply. By using cDNA and genomic probes we demonstrate the presence in testis of a mRNA corresponding to the muscle-specific phosphoglycerate mutase which shows a longer poly(A) tail. This muscle-specific gene is submitted to developmental regulation during testis maturation and begins to be expressed at postnatal day 22, when germ cells start to enter into meiosis. Northern blot and in situ hybridization experiments show that in contrast to what happens during skeletal-muscle differentiation, PGAM-M gene expression during spermatogenesis is not coupled to constitutive phosphoglycerate mutase (PGAM-B) gene repression. Thus, the muscle-specific PGAM-M gene constitutes a meiotic gene and therefore represents a very interesting model to study differential tissue specific gene expression. PMID- 7867620 TI - The gene of chicken axonin-1. Complete structure and analysis of the promoter. AB - We have isolated and characterised the gene encoding the chicken axonal cell adhesion molecule axonin-1. This gene comprises 23 exons distributed over approximately 40 kb. Each of the six immunoglobulin-like domains and the four fibronectin-type-III-like domains of axonin-1 is encoded by two exons. The introns between two domains are exclusively phase I. Their exon/intron borders correspond to the domain borders of the protein, suggesting that the gene of axonin-1 had been generated by exon shuffling. Three transcripts with a length of 4.3 kb, 5 kb, and 8 kb are found, and we provide evidence that they result from alternative use of polyadenylation signals. In situ hybridization revealed co localisation of these transcripts in time and space in the developing chicken retina. Several identical transcription initiation sites were found in retina, brain, and cerebellum by RNase protection assay and anchored polymerase chain reaction. By transfection of HeLa cells, rat PC-12 phaeochromocytoma cells, and chicken embryonic fibroblasts with serially truncated segments of the 5'-flanking region linked to a luciferase reporter gene, we have found that the sequence from -91 to +56 relative to the transcription initiation site is sufficient to promote efficient gene expression. Tissue-specific expression of the axonin-1 gene seems to be regulated in part by sequences more than 1 kb upstream of the transcription initiation site. As revealed by computer analysis, the sequence immediately upstream of exon 1 contains an AP-2 binding site, a tumor phorbol-ester responsive element, and a homeodomain protein binding site, but no canonical TATA box. A second AP-2 binding site and a homeodomain protein binding site are located within exon 1. PMID- 7867622 TI - Promoter region of the transcriptional unit for human alpha 1-chimaerin, a neuron specific GTPase-activating protein for p21rac. AB - alpha 1-chimaerin is a neuron-specific GTPase-activating protein for p21rac, a protein involved in morphological events. The mRNA is highly expressed in certain brain regions. It is also detected in cultured neuronal, but not in non-neuronal cells. As a first step towards understanding the mechanisms underlying this regulation, genomic clones containing the 5'-flanking region of the human alpha 1 chimaerin transcriptional unit were isolated and characterised. A cluster of multiple transcription start sites of alpha 1-chimaerin mRNAs was detected by primer-extension and S1-mapping analyses. The cluster was mapped to nucleotides 464 to -434 (relative to nucleotide A in the initiation codon) in genomic DNA. The 5'-proximal region contained no TATA box, initiator motif and Sp1-binding site. A 210-bp fragment with approximately 110 bp 5'-flanking sequence could function as a minimal promoter upon analysis using hybrid chloramphenicol acetyltransferase reporter constructs and transient transfection. Internal deletion and point-mutation experiments revealed that a GGCCAATC sequence located at nucleotides -519 to -512 was essential for alpha 1-chimaerin promoter activity. Mobility-shift assay showed the specific binding of nuclear factor(s) to this region, which was competed by the oligonucleotides corresponding to wild type but not mutant forms. The data also suggest the existence of possible novel CCAAT-binding factor(s) interacting with the alpha 1-chimaerin CCAAT box binding site. A cell-type-preferred suppressor located in the 5'-distal region was found which may play a role in controlling neuron-specific expression of alpha 1 chimaerin mRNA. These findings of a specific promoter for alpha 1-chimaerin transcription will facilitate further studies on its neuronal-specific expression and function. PMID- 7867623 TI - Determination of kinetic constants for the interaction between the platelet glycoprotein IIb-IIIa and fibrinogen by means of surface plasmon resonance. AB - The binding reaction between purified human platelet glycoprotein IIb-IIIa and fibrinogen was investigated by real-time measurements using the surface-plasmon resonance sensor technology. In these experiments, either glycoprotein IIb-IIIa or fibrinogen was immobilized on a sensor surface. The time-dependent change in surface coverage that occurred immediately upon contact with a solution of the complementary protein was then detected. The ability to record this dynamic event from its initiation allowed the collection of kinetic and thermodynamic data over an extended time period. These data indicated that initially, in fast reaction, a reversible low-affinity complex with an equilibrium dissociation constant, Kd, of 155-180 nM was formed. In a subsequent slower reaction this complex was transformed into a more stable high-affinity complex with a Kd of 20-70 nM. Efficient dissociation of the high-affinity complex could only be induced in the presence of a competitive inhibitor such as RGDV. These data demonstrate that the binding between glycoprotein IIb-IIIa and fibrinogen is not a single monophasic reaction, but is composed of at least two consecutive processes both with their own kinetics. PMID- 7867624 TI - Solution structure of porcine pancreatic procolipase as determined from 1H homonuclear two-dimensional and three-dimensional NMR. AB - Procolipase is the precursor of colipase, which acts as protein cofactor for the activity of pancreatic lipase. The solution structure of procolipase has been determined by 1H NMR using two- and three-dimensional measurements. The secondary structure determination identified two separate three-stranded beta-sheet regions with concomitant hydrogen bond patterns. The tertiary structure of the protein was determined using 863 non-trivial proton--proton distance constraints, 14 hydrogen bond distance constraints and 55 phi and 25 X1 dihedral constraints. The structure that was obtained from distance geometry and energy refinement contains three highly disordered loops as well as a disordered N- and C-terminal region. The remaining part of the structure is well defined with a root-mean-square deviation (rmsd) relative to the average of 0.09 +/- 0.02 nm for backbone atoms (residues 11-30, 37-50, 57-69, 83-89). The protein comprises two identical domains, each containing a three-strand beta-sheet and two disulfide bonds: a 15 residue region in each domain superimposes with 0.07 nm rmsd, measured on backbone atoms. The solution structure is nearly identical to the crystal structure. It is in agreement with previous NMR data and, in combination with these data, supports the current model of procolipase micelle interaction and the lipase activation by colipase. PMID- 7867625 TI - Cloning, properties, site-directed mutagenesis analysis of the subunit structure, tissue distribution and regulation of expression of the type-C eel natriuretic peptide receptor. AB - Eel natriuretic peptide receptor C (NPR-C) was cloned, characterized and found to have a unique interchain disulfide linkage when compared to that of mammalian NPR C. The NPR-C cDNA was obtained from an eel gill cDNA library; the open reading frame codes for a polypeptide of 502 amino acids exhibiting the known features of NPR-C, including a weak ligand specificity and a disulfide-linked homodimeric structure. The deduced amino acid sequence shares approximately 60% similarity with the mammalian NPR-C but it lacks the Gly-rich prosequence present in the mammalian counterparts. Site-directed mutagenesis revealed that eel and mammalian NPR-C are quite different in their interchain disulfide-bonding pattern; eel uses the second Cys residue and mammals the fifth Cys residue for the covalent dimerization. The ligand-binding activity of the extracellular domain is not independent of the short cytoplasmic tail. RNase protection analysis revealed that the eel receptor is highly expressed in the gill and heart and, to a much lesser extent, in other tissues including the brain and intestine. The NPR-C mRNA levels were found to be down-regulated in most tissues when eels were transferred from fresh water to seawater; however, in the anterior intestine, the levels were up-regulated, suggesting that NPR-C plays a role in the adaptation to salinity changes in the euryhaline eel. PMID- 7867626 TI - Binding properties and protease stability of recombinant human nidogen. AB - Recombinant human nidogen was obtained from transfected kidney cell clones as a 150-kDa protein with a three-globule structure. It was modified by sulfation and O-glycosylation and a lower level of N-glycosylation than mouse nidogen. Recombinant nidogens of both species were, however, indistinguishable in their affinities for laminin-1 and a recombinant laminin gamma 1 chain fragment and showed a similar binding to collagen IV and the heparan sulfate proteoglycan perlecan. The two nidogens were also equivalent in the promotion of ternary complex formation between these ligands, indicating that this function has been conserved during mammalian evolution. Fewer zinc-binding sites could be identified in human nidogen and correlated with a lower capacity of zinc to prevent binding to laminin and collagen IV. Most remarkable was the greater sensitivity of human nidogen to endogenous proteolysis in cell culture, yielding fragments of 90-145 kDa. Studies with several exogenous proteases, including thrombin and leucocyte elastase, showed lack of stability of the N-terminal globular domain G1 in contrast to what was found for mouse nidogen. Since such degradation could be important for basement membrane remodelling, this difference between human and mouse may be biologically significant. PMID- 7867627 TI - Characterization of the equilibrium between blocked and closed states of muscle thin filaments. AB - We recently proposed a three-state model for the regulation of actomyosin interaction by tropomyosin and troponin (Tm.Tn). In this model, the thin filament exists in rapid equilibrium between the following three states: blocked, which cannot bind myosin significantly; closed, which can bind myosin weakly to form the A-state; open, which can bind both to form the A-state and isomerize to the strongly bound R-state. In this study, we demonstrate that the equilibrium between the blocked and closed states is calcium sensitive with an equilibrium constant, KB, of 0.3 and > or = 10 at pCa 8.9 and 4.6, respectively. The pCa dependence of KB is typical of that for calcium binding to thin filaments with a mid-point at pCa 5.6 and a Hill coefficient of 1.8. KB is independent of ionic strength over the range 0.4-0.06 M but increases dramatically below 0.05 M to > or = 10 at 0.01 M suggesting loss of the blocked state at low ionic strength. The blocked state also has reduced occupancy at high temperatures. KB, in the absence of calcium, increases from 0.2 at 5 degrees C to 0.6 at 40 degrees C. PMID- 7867628 TI - The pH-dependent changes of the enzymic activity and spectroscopic properties of iron-substituted manganese superoxide dismutase. A study on the metal-specific activity of Mn-containing superoxide dismutase. AB - Manganese-containing superoxide dismutases (Mn-SODs) and iron-containing superoxide dismutases (Fe-SODs) from aerobic bacteria often show high metal specificity for their enzymic activities by a standard assay system using xanthine-xanthine oxidase and cytochrome c. In this study, we have attempted to characterize the structural basis of the metal specificity of manganese containing SOD (Mn-SOD) using Fe-substituted Mn-SOD prepared from apo-Mn-SOD from Serratia marcescens. The Fe3+ content of the Fe-substituted enzyme was 1.71 +/- 0.14 mol/mol dimer and the specific activity was 34.8 +/- 4.8 units.mg protein 1.mol Fe3+(-1).mol subunit-1. Fe-substituted Mn-SOD was found to react with the superoxide anion at pH 8.1 with a second-order rate constant of 6 x 10(6) M-1 s 1, which is approximately 1% of that of native Mn-SOD at the same pH. However, the rate constant increased with decreasing pH to approximately 10% (5 x 10(7) M 1 s-1) that of native Mn-SOD at pH 6.0 with a pK of 7.0. The visible absorption spectrum and EPR spectrum of Fe-substituted Mn-SOD also showed pH-dependent changes with pK values of 6.6 and 7.2, respectively. Similarly, the affinity of the azide ion, an analog of the superoxide ion, for iron of Fe-substituted Mn-SOD increased with decreasing pH, with a pK value of 7.0 (e.g. Kd = 0.1 mM at pH 6.2 and 0.9 mM at pH 8.2). The similarity of these pK values suggests that the activity, the spectral changes and the affinity of the azide ion for iron are derived from the same change in the metal environment. After comparison with the reported pK values (around 9) of similar pH-dependent changes in the spectra, the enzymic activity and the affinity of azide for iron of Fe-SOD from Escherichia coli, we proposed that the difference in the pK values of a hydroxide ion binding to iron between Fe-substituted Mn-SOD and Fe-SOD may cause the different pH dependencies of these changes in each SOD. PMID- 7867629 TI - Role of amino acid sequences flanking dibasic cleavage sites in precursor proteolytic processing. The importance of the first residue C-terminal of the cleavage site. AB - The amino acid sequences flanking 352 dibasic moieties contained in 83 prohormones and pro-proteins listed in a database were examined. Frequency calculations on the occurrence of given residues at positions P6 to P'4 allowed us to delineate a number of features which might be in part responsible for the in vivo discrimination between cleaved and uncleaved dibasic sites. These include the following: amino acids at these positions were characterized by a large variability in composition and properties; no major contribution of a given precursor subsite to endoprotease specificity was observed; some amino acid residues appeared to occupy preferentially certain precursor subsites (for instance, Met in P6 and P3, Asp and Ala in P'1, Pro in P6, Gly in P3 and P'2 etc.) whereas some others appeared to be excluded. Most amino acid residues occupying the P'1 position in these precursor cleavage sites were tolerated. But the beta-carbon branched side chain residues (Thr, Val, Leu, Ile) and Pro, Cys, Met and Trp were either totally excluded or poorly represented, suggesting that they might be unfavourable to cleavage. The biological relevance of these observations to the efficacy of dibasic cleavage by model propeptide convertases was in vitro tested using both pro-ocytocin convertase and Kex2 protease action on a series of pro-ocytocin related synthetic substrates reproducing the Pro7- >Leu15 sequence of the precursor in which the Ala13 residue (P'1 in the LysArg Ala motif) was replaced by various amino acid residues. A good correlation was obtained on this model system indicating that P'1 residue of precursor dibasic processing sites is an important feature and may play the role of anchoring motif to S'1 convertase subsite. We tentatively propose that the present database, and the corresponding model, may be used for further investigation of dibasic endoproteolytic processing of propeptides and pro-proteins. PMID- 7867630 TI - Hepatic fatty acid metabolism as a determinant of plasma and liver triacylglycerol levels. Studies on tetradecylthioacetic and tetradecylthiopropionic acids. AB - To investigate the importance of factors influencing substrate availability for triacylglycerol biosynthesis on lipoprotein metabolism, the effects of two opposite-acting sulphur-substituted fatty acid analogues, tetradecylthioacetic acid and tetradecylthiopropionic acid were studied. Administration of tetradecylthioacetic acid to rats resulted in a reduction of plasma levels of triacylglycerols (44%) and cholesterol (26%). This was accompanied by a reduction in very-low-density lipoprotein (VLDL) triacylglycerols (48%), VLDL cholesterol (36%), low-density lipoprotein (LDL) cholesterol (36%) and high-density lipoprotein (HDL) triacylglycerols (50%), whereas HDL cholesterol levels did not change. Subsequently, the HDL/LDL-cholesterol ratio increased by 40%. The cholesterol-lowering effect was accompanied by a reduction in hydroxymethylglutaryl CoA (HMG-CoA) reductase activity (37%). Both mitochondrial and peroxisomal fatty acid oxidation increased (1.7-fold and 5.3-fold, respectively). Furthermore, there was a significant negative correlation between plasma triacylglycerols and mitochondrial fatty acid oxidation. Hepatic triacylglycerol synthesis was retarded, as indicated by a decrease in VLDL triacylglycerol secretion (40%), and by a reduced liver triacylglycerol content (29%). The activities of lipoprotein lipase and hepatic lipase in post-heparin plasma were not affected. Microsomal and cytosolic phosphatidate phosphohydrolase activities were inhibited (28% and 70%, respectively). Hepatic malonyl-CoA levels decreased by 29% and the total activity of acetyl-CoA carboxylase was reduced (23%). In hepatocytes treated with tetradecylthioacetic acid, mitochondrial fatty acid oxidation increased markedly (100%) and triacylglycerol secretion was reduced (40%). In tetradecylthiopropionic-acid-treated rats, a significant increase in both plasma and VLDL triacylglycerols was found (46% and 72%, respectively) but VLDL triacylglycerol secretion was unaffected. However, no effect on either plasma or lipoprotein cholesterol levels was seen. Mitochondrial fatty acid oxidation was decreased by 50% and hepatic triacylglycerol levels increased by 33%. In hepatocytes exposed to tetradecylthiopropionic acid, triacylglycerol synthesis increased (100%) while triacylglycerol secretion and fatty acid oxidation remained unaltered. The results illustrate that lipoprotein triacylglycerol levels can be modulated by changes in the availability of fatty acid substrate for triacylglycerol biosynthesis, mainly by affecting mitochondrial fatty acid oxidation. In addition, we demonstrate that suppression of rat hepatic HMG-CoA reductase activity during treatment with tetradecylthioacetic acid may contribute to a cholesterol-lowering effect. PMID- 7867631 TI - Degradation of the D1 protein of photosystem-II reaction centre by ultraviolet-B radiation requires the presence of functional manganese on the donor side. AB - The in vivo effects of ultraviolet-B radiation (280-320 nm) on photosystem-II activity and degradation of the D1 protein are investigated and compared with the in vitro results on isolated thylakoids and other detergent-extracted photosystem II preparations. A cleavage site in the second transmembrane segment of the D1 protein, giving rise to a 20-kDa C-terminal and a 13-kDa N-terminal fragment pair, is detected after irradiation of entire leaves as well as in all photosystem-II preparations, irrespective of their actual ability to evolve oxygen but depending on the presence of Mn ions associated with the water splitting system. Damage to the plastoquinone moiety, observed by other authors, is confirmed and is proposed to be responsible for the impairment of electron transport activity, but not for the observed cleavage of the D1 protein. PMID- 7867632 TI - [3H]7-azido-4-isopropylacridone labels Cys159 of the bovine mitochondrial ADP/ATP carrier protein. AB - Acridones (9-azaanthracen-10-ones), especially halogen-substituted acridone carboxylic acids are efficient inhibitors of [14C]ADP binding to the bovine mitochondrial ADP/ATP-carrier protein. 7-Iodoacridone-4-carboxylic acid displaces [14C]ADP in a competitive manner, which indicates that both compounds share an identical binding site. Upon ultraviolet illumination, 7-azido-4-[1',2' 3H]isopropyl-acridone binds covalently to the ADP/ATP-carrier protein. By sequencing of its proteolytic fragments, radioactivity was detected in Cys159. This amino acid is located close to Lys162, a target of 2-azido-[alpha-32P]ADP [Dalbon, P., Brandolin, G., Boulay, F., Hoppe, J. & Vignais, P. V. (1988) Biochemistry 27, 5141-5149]. PMID- 7867633 TI - Membrane lipid composition and cell size of Acholeplasma laidlawii strain A are strongly influenced by lipid acyl chain length. AB - The small, cell-wall-less prokaryote Acholeplasma laidlawii strain A-EF22 could grow with membrane lipids having an average acyl chain length Cn varying over 14.5- almost 20 carbons by exogenous supplementation with selected fatty acids. For 16 < Cn < 18, the cells grew with lipids containing 100% (mol/100 mol) monounsaturated acyl chains, whereas for Cn < 16 and Cn > 18, cell growth only occurred with gradually lower fractions of unsaturated chains. Cn was actively increased and decreased by chain elongation or de novo fatty acid synthesis upon incorporation of short-chain and long-chain fatty acids, respectively. The membrane lipid composition was strongly affected by the acyl chain length and unsaturation, and the metabolic responses are readily explained as a regulation mechanism based on the established phase equilibria of the individual lipids in the A. laidlawii membrane. Monoglucosyldiacylglycerol (Glc-acyl2-Gro) was the dominating lipid with short chains but the fraction of this lipid decreased with increasing Cn, correlating with the decreasing lamellar to nonlamellar phase transition temperatures for this lipid. The fractions of diglucosyldiacylglycerol (Glc2-acyl2Gro) and phosphatidylglycerol (PtdGro), forming lamellar phases only, increased with increasing Cn over the entire chain-length interval. A weaker correlation was usually observed between the relative amount of a lipid and the extent of chain unsaturation; however, the fractions of Glc2-acyl2Gro and PtdGro increased clearly with an increasing degree of unsaturation. Moreover, the synthesis of the nonbilayer-forming lipids acyl2Gro and monoacyl-Glc-acyl2Gro was strongly stimulated by a high degree of chain saturation. Concomitantly, the phase equilibria of Glc-acyl2Gro are shifted towards lamellar phases at the growth temperature. The fraction of the three potentially nonbilayer-forming lipids varied over 10-80% (mol/100 mol) total lipids as a function of the acyl chain composition. The combined molar fractions of the three phospholipids increased strongly with chain unsaturation. However, the fraction of phosphate moieties in the different lipids was constant over the entire chain-length interval. It is concluded that the regulation of the membrane lipid composition aims at maintaining similar phase equilibria and surface charge densities of the lipid bilayer. The size of A. laidlawii cells was changed in a systematic manner and correlated qualitatively with the packing properties of the lipids. Cell diameters were increased by an increase in acyl chain length and saturation, and was affected by additives such an n-dodecane and acyl2Gro. PMID- 7867634 TI - Relationship of subunit 8 of yeast ATP synthase and the inner mitochondrial membrane. Subunit 8 variants containing multiple lysine residues in the central hydrophobic domain retain function. AB - A molecular genetic approach has been used to test the proposition that the central hydrophobic domain of yeast mitochondrial ATP synthase subunit 8 represents a transmembrane stem in contact with the lipid bilayer. The rationale for this approach is the general inability of membrane bilayers to accomodate unshielded charged residues of polypeptide chains. Non-polar residues at several positions within the central hydrophobic domain of subunit 8 were replaced with the positively charged amino acid lysine. This was done in an attempt to disrupt subunit 8 function, and thereby determine the boundaries of the putative transmembrane stem. Each subunit 8 variant was allotopically expressed in vivo as a mitochondrial import precursor encoded by a nuclear gene. It was found that all variants, which included proteins carrying two lysines at various positions in the hydrophobic domain, exhibited the ability to restore growth of subunit-8 deficient cells on the non-fermentable substrate ethanol. This indicated that the function of none of these subunit 8 variants was severely compromised. There was also no detectable change in the proteolipid characteristics of subunit 8, as defined by the chloroform/methanol solubility properties of variant proteins extracted from membranes following import into isolated mitochondria. These data suggest that subunit 8 is located in a hydrophobic niche in the mitochondrial ATP synthase, probably in contact with other protein subunits of the complex. We conclude that the function of subunit 8 does not necessarily require it to be integrated within the inner mitochondrial membrane, in contact with the lipid bilayer. Our findings also suggest that hydropathy plots, indicating hydrophobic domains within polypeptides, cannot reliably be interpreted as transmembrane helices in the absence of independent evidence. PMID- 7867635 TI - Reciprocal regulation of prothrombin secretion and tyrosine aminotransferase induction in hepatocytes. AB - Multicellular spheroids of hepatocytes are known to maintain liver functions for a long period. Rat hepatocytes were isolated to form spheroids by rotation culture and immobilized within calcium alginate. Immobilized spheroids had a much higher extent of tyrosine aminotransferase induction, which is one of the liver specific differentiated functions, than immobilized non-aggregated cells, while the spheroids secreted significantly less prothrombin than non-aggregated cells. Co-culture of hepatocytes and non-parenchymal liver cells in a monolayer enhanced tyrosine aminotransferase induction and suppressed prothrombin secretion, while conditioned medium prepared from non-parenchymal cells greatly stimulated tyrosine aminotransferase induction and suppressed the prothrombin secretion and DNA synthesis in monolayer-cultured hepatocytes. Prothrombin secretion in hepatocytes was subjected to cell-density-dependent regulation. In a similar manner to other growth-related functions, prothrombin secretion was stimulated at low cell density. It has been reported that thrombin activates the zymogen of hepatocyte growth factor activator [Shimomura, T., Kondo, J., Ochiai, M., Naka, D., Miyazawa, K., Morimoto, Y. & Kitamura, N. (1993) J. Biol. Chem. 268, 22,927 22,932]. Therefore, prothrombin secretion could be one of the growth-related functions and involved in wound healing and liver regeneration. PMID- 7867636 TI - Sequence analysis by NMR spectroscopy of the peptide lantibiotic epilancin K7 from Staphylococcus epidermidis K7. AB - The amino acid sequence of the novel lantibiotic epilancin K7 from Staphylococcus epidermidis K7 was determined by NMR spectroscopy. NMR spectroscopy was used because sequencing by conventional Edman degradation techniques was prohibited by internal sequence blocks owing to the presence of modified residues. Epilancin K7 consists of 31 residues, including two alpha,beta-didehydroalanine (one-letter code U) and two alpha,beta-didehydrobutyrine (O) residues, one lanthionine (A-S A), two beta-methyllanthionines (A*-S-A), and six lysines. Epilancin K7 has a molecular mass of 3032 +/- 1.5 Da. The amino acid sequence of epilancin K7 was derived from both through-space dipolar proton-proton interactions and through bond scalar proton-carbon interactions as detected by two-dimensional 1H-NOESY, 1H-ROESY and three-dimensional 1H-TOCSY-NOESY, and by two-dimensional 1H,13C heteronuclear multiple-bond correlation spectroscopy, respectively. The sequence is as follows: [sequence: see text] The N-terminal residue X partly resembles an alanine but its exact nature is unclear. The organization of the sulfide-bridge containing (beta-methyl-)lanthionines was revealed by 1H-NMR and 1H,13C-NMR spectroscopy. Epilancin K7 has a linear structure and a high positive net charge, and therefore is classified as a type-A lantibiotic. NMR analysis of a degraded though still active form of epilancin K7 showed that two N-terminal residues of epilancin K7 were missing, owing to decomposition at the alpha,beta-didehydro alanine at position 3; it was called the epilancin K7-(3-31)-peptide (peptide fragment of epilancin K7 consisting of positions 3-31). The usefulness of three dimensional 1H-TOCSY-NOESY, and two-dimensional 1H,13C-heteronuclear multiple bond correlation spectroscopy at natural abundance for the study of (modified) polypeptides is demonstrated. PMID- 7867637 TI - Purification and characterization of amyloid-related transthyretin associated with familial amyloidotic cardiomyopathy. AB - Analysis of amyloid fibril material associated with familial amyloidotic cardiomyopathy revealed that it contains a mixture of transthyretin-related polypeptides. The major protein band in SDS/polyacrylamide gel corresponding to a molecular mass of 14.5 kDa, consists of transthyretin fragments starting at positions 46, 49 and 59, the latter not previously identified, and one blocked fragment derived from the N-terminal part of transthyretin. In reverse-phase HPLC, the major fragment recovered was that starting at Thr49, indicating a trypsin-like cleavage (Lys at position 48). Two minor bands, corresponding to 17 kDa and 35 kDa, contained proteins with blocked N-termini, and migrated as monomeric and dimeric transthyretin, respectively. A 13-kDa protein band was found to contain transthyretin with a ragged N-terminus, mainly starting at positions 2 and 5. Three more bands, corresponding to 10, 25 and 29 kDa, consist of transthyretin molecules with blocked N-termini and most likely of aggregates of truncated molecules. A point mutation of amyloid transthyretin was identified at position 111 (Met instead of Leu in normal serum transthyretin) which confirms the mutation found for Danish siblings with familial amyloidotic cardiomyopathy. However, the presence of a non-variant amyloid transthyretin was also observed, indicating that the Danish kindred is heterozygous with respect to this point mutation. Isoelectric focusing of the amyloid fibril material resolved multiple protein bands ranging over pH 4.5-6.5, confirming heterogeneities. Methanol extraction of the cardiac amyloid fibril material prior to the purification steps reveals a methanol-soluble substance amounting to about 10% (by mass dry material) of the amyloid fibril material. A yellow substance in this fraction shows absorbance maxima (270, 280 and 430 nm) similar to those observed for transthyretin in normal serum. Gas chromatography/mass spectrometry of the methanol extract revealed the presence of saturated fatty acids (C14:0, C16:0 and C18:0 in the corresponding ratio 2:8:5) and polyunsaturated fatty acids (C16:1, C18:1, C18:2 and C20:4 in the corresponding ratio of 1:2:1:1) as further constituents of the amyloid fibril material. PMID- 7867638 TI - Identification by UV cross-linking of oligo(U)-binding proteins in mitochondria of the insect trypanosomatid Crithidia fasciculata. AB - RNA editing in trypanosomes is the process of insertion and deletion of U residues at specific sites of mitochondrial transcripts mediated by short guide RNAs (gRNAs) that have a 3' oligo(U) extension. Here we describe the identification by UV cross-linking of proteins present in mitochondrial extracts from Crithidia fasciculata with a high affinity for gRNAs, and the characterization of the binding specificity. A 65-kDa protein binds to gRNAs provided they are equipped with a U tail, to post-transcriptionally labelled mitoribosomal 9S and 12S RNAs that also possess a 3' terminal stretch of U residues, and to free oligo(U) sequences with a minimal length of 23-29 nucleotides. It does not bind to a number of control RNAs, one of which has an internal U stretch of 13 residues. Poly(U), but not poly(C) or total yeast RNA, efficiently competes for binding to gRNA. Proteins of 88 kDa and 30 kDa also bind to gRNAs with a U tail, to mitochondrial ribosomal RNAs and to oligo(U). These proteins, however, require longer oligo(U) for binding (> 39 nucleotides) and they also have an affinity for other U-rich RNAs and poly(C). For comparison, part of the analysis was also carried out with a mitochondrial extract from Trypanosoma brucei. In this organism, gRNA-binding proteins of 83 kDa and 64 kDa were found with the same preference for 3'-terminal oligomeric U stretches as the C. fasciculata 65-kDa protein, whereas the binding specificity of a 26-kDa protein resembled that of the C. fasciculata 88-kDa and 30-kDa proteins. The possible involvement of the proteins in the editing process is discussed. PMID- 7867639 TI - C-terminus or juxtamembrane deletions in the insulin receptor do not affect the glucose-dependent inhibition of the tyrosine kinase activity. AB - We have previously shown, in rat-1 fibroblasts which stably overexpress high levels of human insulin receptor (HIR), that high glucose levels induce an inhibition of insulin receptor tyrosine kinase (IRK) activity [Berti, L., Mosthaf, L., Kellerer, M., Tippmer, S., Mushack, J., Seffer, E., Seedorf, K., Haring, H. (1994) J. Biol. Chem. 269, 3381-3386]. This effect appears to be mediated through activation of protein kinase C and phosphorylation of the receptor beta-subunit on threonine or serine residues. The aim of the present study was to determine whether the juxtamembrane region or the C-terminus tail of the receptor are involved in the IRK modulation by glucose. In these domains increased serine and threonine phosphorylation was observed after phorbol ester or insulin stimulation of cells, and a regulatory function for IRK activity seems conceivable. We used an antibody directed against one potential regulatory site in the C-terminus tail, i.e. PSer1315, to study the effect of glucose. An increased signal was detected in HIR from rat-1 fibroblasts treated with phorbol 12-myristate 13-acetate or glucose (25 mM). To investigate whether this site in the C-terminus is essential for glucose-dependent IRK inhibition, rat-1 fibroblasts stably overexpressing a C-terminus-truncated human insulin receptor lacking 43 amino acids (HIR delta CT) were studied in parallel with cells expressing the wild-type receptor. As described earlier, HIR delta CT has lost the ability to stimulate glucose uptake. Glucose (25 mM) inhibited the insulin effect on the autophosphorylation of both receptors to a similar extent. Thus, glucose (25 mM) stimulates phosphorylation of Ser1315, however, this appears not to mediate the inhibitory effect on IRK. To test whether serine residues 955/956 and 962/964 in the juxtamembrane region of the insulin receptor are involved in the inhibitory effect of glucose, 293 cells transiently transfected either with wild-type HIR or HIR with a juxtamembrane deletion spanning amino acids 954-965 [des-(954-965)-HIR] were studied in parallel. As described earlier, the des-(954 965)-HIR has lost the ability to stimulate PI-3 kinase. However, 25 mM glucose equally inhibited the insulin effect on tyrosine phosphorylation of the receptor. Together, the data suggest that the regulatory serine or threonine phosphorylation site(s) involved in the inhibitory effect of hyperglycemia are neither located in the C-terminus nor in the juxtamembrane region of the insulin receptor beta subunit. PMID- 7867640 TI - Degradation of proteasomes by lysosomes in rat liver. AB - Proteasomes are high-molecular-mass multisubunit complexes which are believed, either by themselves or as a part of the 26S proteinase complex, to play a central role in extralysosomal pathways of intracellular protein breakdown. We have addressed the degradation of proteasomes in rat liver, investigating the possible role of lysosomes. Affinity-purified antibodies against rat liver proteasomes were used for immunoblot analysis of isolated lysosomes. Although proteasomes are not found in lysosomes from normally fed rats, they were found to accumulate in lysosomes of rats treated with leupeptin (an inhibitor of lysosomal proteases) and could also be detected in lysosomes isolated from livers of starved (24 h) rats. Proteinase-K treatment of these fractions, as well as immunogold procedures, show that a proportion of the proteasomes are inside lysosomes. Comparison of the amount of proteasomes found in lysosomes by immunoblotting with their experimentally determined half life (8.3 days) is consistent with an important role of these organelles in the degradation of rat liver proteasomes. Nevertheless, these data do not exclude the possibility that some nonlysosomal degradation of proteasome components also occurs. Since proteasomes were localized in autophagic vacuoles, it is likely that they are taken up mainly by nonselective autophagy. However, using an in vitro system, it was found that, under conditions of starvation, proteasomes may also be taken up into lysosomes and degraded via the heat-shock cognate protein of 73 kDa (hsc73) mediated transport. PMID- 7867641 TI - Evidence for transcriptional induction of the liver fatty-acid-binding-protein gene by bezafibrate in the small intestine. AB - The effect of bezafibrate on cytosolic fatty-acid-binding-protein (FABPc) production along the small intestine has been investigated in mice. This drug increased the intestinal fatty-acid-binding-protein (I-FABPc) and liver fatty acid-binding-protein (L-FABPc) mRNA levels in the duodenum. The extents of induction in the duodenum and in the liver are similar. However, the degree of stimulation gradually decreases along the length of the gut, no effect being found in the ileum. An efficient absorption of this drug as early as the proximal part of the small intestine may explain this phenomenon. The L-FABPc gene is silent in terminal ileum of mice, but a direct infusion of bezafibrate into the ileum switches it on. We used this original model to follow the time course of induction of the L-FABPc gene by bezafibrate. L-FABPc mRNA was first detected 4 h after fibrate infusion, reached a maximum level at 16 h and subsequently decreased at 24 h. This induction was totally blocked by cycloheximide. Sunflower oil also caused small increases in the L-FABPc mRNA levels. The transcriptional origin of the induction triggered both by bezafibrate and sunflower oil was demonstrated by run-on assays. These data indicate that (a) the transcription of the L-FABPc gene is induced by bezafibrate via de novo protein synthesis and (b) components of sunflower oil can transcriptionally activate the L-FABPc gene. Our results also demonstrate that the mouse terminal ileum is a useful system for studying the regulation of L-FABPc gene expression both in vivo and in vitro. PMID- 7867643 TI - pH-induced conformational perturbation in horseradish peroxidase. Picosecond tryptophan fluorescence studies on native and cyanide-modified enzymes. AB - The fluorescence-decay characteristics of the single tryptophan present in horseradish peroxidase (HRP) have been studied using dye-laser pulses and single photon counting techniques. The decay was found to be dominated by a picosecond lifetime component, with small contributions from two other lifetime components in the nanosecond range. The distance of the tryptophan residue was estimated from the fluorescence-energy transfer to the heme moiety using Forster's theory. The tryptophan residue was found to be approximately 1.2 nm from the heme moiety at neutral pH. Detailed analysis of the fluorescence-decay profiles using the maximum-entropy method (MEM) has been carried out. The results of the MEM analysis also showed a maximum amplitude peak at approximately 45 ps (at pH approximately 7) with a very small (< 5%) contribution from two other components. Similar results were obtained with the cyanide derivative of the enzyme (HRPCN) where the major lifetime component was found to be 58 ps at neutral pH. The picosecond component of fluorescence lifetimes of native HRP as well as of HRPCN were found to increase with decrease in pH in the range pH 6-3.5. Moreover, the native enzyme showed significant increase in the magnitude of this fast lifetime component at pH above 8. Such increase in the major lifetime component possibly indicated a conformational perturbation caused by pH change in the enzyme. However, the pH dependence of HRPCN, which is devoid of alkaline transition, showed that the shortest lifetime component remains almost unchanged over the pH range 6-11. This result showed that the alkaline transition in native HRP is associated with a structural change in the distal region of the heme center, which is absent in the cyanide-ligated enzyme. The results have been discussed with respect to understanding the pH-induced effects associated with salt bridge and hydrogen-bonding network in HRP. PMID- 7867642 TI - Substitution of Arg230 and Arg233 in Escherichia coli elongation factor Tu strongly enhances its pulvomycin resistance. AB - Pulvomycin is a strong inhibitor of protein synthesis, known to prevent the binding of aminoacyl-tRNA to elongation factor Tu.GTP (EF-Tu.GTP). Recently, three pulvomycin-resistant mutant strains have been isolated by targeted mutagenesis of the tufA gene resulting in EF-Tu substitutions at positions 230, 333 or 334. In order to analyze the functions of arginine residues located in domain II, with respect to pulvomycin resistance and the interaction with aminoacyl-tRNA, we have investigated the effect of the substitutions of the highly conserved residues Arg230 and Arg233 by site-directed mutagenesis. We have purified two mutants species, [R233S]EF-TuHis and [R230V, R233F]EF-TuHis, both with a C-terminal histidine extension to enable purification by Ni2+ affinity chromatography. In this study, we describe the in vitro characterization of these mutant proteins. The results show that the concomitant substitution of residues at positions 230 and 233, dramatically increases the pulvomycin resistance. Preliminary evidence is presented that protein synthesis is inhibited by an EF Tu.GDP.pulvomycin complex rather than by EF-Tu.GTP.pulvomycin. Moreover, the mutant [R230V, R233F]EF-TuHis shows a stronger protection of the ester bond of aminoacyl-tRNA than wild-type EF-Tu. PMID- 7867644 TI - Determination of haem electronic structure in His-Met cytochromes c by 13C-NMR. The effect of the axial ligands. AB - The assignment of 13C resonances of nuclei alpha to the haem in horse ferricytochrome c is completed and the Fermi contact shifts are evaluated at 30 degrees C and 50 degrees C using empirical magnetic susceptibility tensors to correct for dipolar interactions. The Fermi contact shifts are fitted to a model of molecular orbitals of eg symmetry, which are subject to a rhombic perturbation. A similar analysis is performed using published data for Pseudomonas aeruginosa cytochrome c551. The relationship between the orientation of the effective g tensor and that of the rhombic perturbation in these proteins is shown to agree with theoretical predictions. A comparison between the orientation of the rhombic perturbations and the crystal structures of horse cytochrome c and P. aeruginosa cytochrome c551 reveals that the orientation of the histidine and methionine axial ligands dominates the rhombic perturbation and that the two ligands have approximately equal influence. The magnitude of the perturbation shows that the orientation of the axial ligands has little effect on the haem redox potential. However, the relationship that is established between the magnetic susceptibility tensor, the partially filled haem molecular orbitals, and the orientation of the haem ligands offers a new source of precise structural information. PMID- 7867645 TI - Refined crystal structure of the interleukin-1 receptor antagonist. Presence of a disulfide link and a cis-proline. AB - Interleukin-1 (IL-1) molecules are cytokines involved in the acute-phase response against infection and injury. Three naturally occurring IL-1 molecules are known, two agonists: IL-1 alpha and IL-1 beta, and one antagonist, the IL-1 receptor antagonist (IL-1ra). Although IL-1 action protects the organism by enhancing the response to pathogens, its overproduction can lead to pathology and has been implicated in disease states that include septic shock, rheumatoid arthritis, graft versus host disease and certain leukemias. The crystal structure of IL-1ra has been solved at 0.21-nm resolution by molecular replacement using the IL-1 beta structure as a search model. The crystals contain two independent IL-1ra molecules which are very similar. IL-1ra has the same fold as IL-1 alpha and IL-1 beta. The fold consists of twelve beta-strands which form a six-stranded beta barrel, closed on one side by three beta-hairpin loops. Cys69 and Cys116 are linked via a disulfide bond and Pro53 has been built in the cis-conformation. Comparison of the IL-1ra structure with the IL-1 alpha and IL-1 beta structures present in the Protein Data Bank shows that a putative receptor interaction region, involving the N-terminus up to the beginning of strand beta 1 and the loops D and G, is very different in the three IL-1 molecules. Other putative interaction regions, as identified with mutagenesis studies, are structurally conserved and rigid, allowing precise and specific interactions with the IL-1 receptor. PMID- 7867646 TI - The thermosome of Thermoplasma acidophilum and its relationship to the eukaryotic chaperonin TRiC. AB - A high molecular-mass protein complex from the archaebacterium Thermoplasma acidophilum, referred to here as the 'thermosome', is built from two subunits (M(r) 58 and 60). The thermosome has been purified to homogeneity. The molecular mass of the native complex was determined to be 1061 +/- 30 Da by scanning transmission electron microscopy. It shows a weak ATPase activity and is able to bind denatured polypeptides. Averages obtained from electron micrographs of negatively stained molecules in the end-on and side-on orientations, respectively, were compared with those of the t-complex polypeptide 1 ring complex (TRiC), isolated from bovine testes. Both molecules consist of two stacked pseudo eightfold symmetric rings which build up a cylindrical particle with a large cavity in the center. Sequence alignments of peptides generated from both subunits of the thermosome and different subunits of TRiC reveal a high partial similarity to each other and to the archaebacterial chaperonin thermophilic factor 55 from Sulfolobus shibatae as well as to eukaryotic TCP1 proteins. These striking structural similarities confirm the proposition that all these molecules belong to a single protein family which is structurally and functionally related to the GroEL class of molecular chaperones. PMID- 7867647 TI - Purification and characterization of the periplasmic nickel-binding protein NikA of Escherichia coli K12. AB - The nik operon of Escherichia coli encodes a periplasmic binding-protein dependent transport system specific for nickel. In this report, we describe the overproduction of the periplasmic nickel-binding protein NikA by cloning the nikA gene into an overexpression vector, pRE1. NikA was purified free of nickel to near homogeneity from the periplasm by hydrophobic and ion-exchange chromatography. N-terminal amino acid sequencing confirmed that the leader peptide of NikA had been removed. The nickel-binding properties of the protein has been studied by monitoring the quenching of intrinsic protein fluorescence. NikA binds one atom of nickel/molecule of protein with a dissociation constant (Kd) of less than 0.1 microM. Other metals (cobalt, copper, iron) are bound at least 10-fold less tightly. The high specificity for Ni2+ is also demonstrated by high-performance immobilized-metal-ion affinity chromatography. Biosynthesis of NikA occurred only under anaerobic conditions and was dependent on the general anaerobic regulator FNR. It was repressed by the presence of 250 microM Ni2+ in the growth medium and was not affected by either 30 mM formate or 100 mM nitrate. Anaerobically grown wild-type strain MC4100 contains about 23,000 molecules of NikA/cell. In addition to the effect on nickel transport, nikA mutation affects also the nickel sensing in Tar-dependent repellent chemotaxis. PMID- 7867648 TI - Duodenase, a new serine protease of unusual specificity from bovine duodenal mucosa. Purification and properties. AB - In this paper, data are presented on purification and properties of a new serine endopeptidase (duodenase) isolated from bovine duodenum mucosa. The enzyme has been purified to homogeneity by combinations of ammonium sulphate fractionation, carboxymethyl-cellulose 52 chromatography, and affinity chromatography on Sepharose 4B with Kunitz soybean trypsin inhibitor as a ligand. Some physicochemical properties of this protease have been investigated. The molecular mass of the purified duodenase was determined to be 29 +/- 0.5 kDa by SDS/PAGE and G-2000 SW column chromatography. The enzyme molecule is a single chain and the native enzyme is a monomeric protein. Its isoelectric point was estimated to be 10 +/- 0.2. Duodenase has two forms (I and II) which possess similar properties but differ in their amino acid composition. The new protease is a glycoprotein and contains approximately 3.5% sugars. The enzyme displays trypsin like and chymotrypsin-like activities and hydrolyzes the amide bonds of substrates having Lys, Arg, Tyr, Phe and Leu residues at the P1 position. Duodenase is most active at pH 7.9-8.2. Duodenase was irreversibly inhibited by diisopropylphosphofluoridate and phenylmethanesulphonyl fluoride, indicative of an active-site serine in this protease. alpha-N-Tosyl-L-lysine chloromethane and alpha-N-tosyl-L-phenylalanine chloromethane, which react with an active His, caused marked inhibition of trypsin-like and chymotrypsin-like activities of duodenase. The enzyme activity was strongly suppressed by trypsin inhibitors from different sources (soybeans, bovine lungs and Lima beans). Chicken egg white ovomucoid had no effect on the duodenase activity. The N-terminal sequence of the native duodenase (24 amino acid residues) shows high similarity with those of human and murine cytotoxic T-lymphocyte granzymes, human leukocyte cathepsin G and rat mast cell chymases. The biological role of duodenase is discussed. PMID- 7867649 TI - Duodenase, a new serine protease of unusual specificity from bovine duodenal mucosa. Primary structure of the enzyme. AB - The complete amino acid sequence of duodenase, a new serine endopeptidase from bovine duodenal mucosa, has been determined. The sequence was reconstructed by the automated sequence analysis of the peptides obtained after cleavage with trypsin, Staphylococcus aureus V8 protease, cyanogen bromide and duodenase. The enzyme is composed of 226 amino acid residues yielding a molecular mass of 29.06 kDa. The presence of six cysteine residues and one potential sugar-chain-binding site at Asn50 was revealed. A predicted catalytic triade characteristic of the serine proteases was traced in the duodenase primary structure at the corresponding positions (His44, Asp87 and Ser181 in the sequence). Comparison of the sequence of duodenase with the other known primary structures of mammalian serine proteinases reveales the duodenase identity to granzymes from human and mice, human cathepsin G and mast cell chymases from rat, and gives an overall sequence identity of 47-55% with the mentioned enzymes. Alignment of the known serine protease and duodenase primary structures showed unique amino acid residues within the duodenase substrate-binding pocket at positions 189 (Asn) and 226 (Asp) (the bovine chymotrypsinogen A numbering). These results are discussed with respect to the relation between the duodenase unique residues within the primary specificity pocket S1 and the unusual dual specificity of the enzyme. PMID- 7867650 TI - Enzymic remodelling of the N- and O-linked carbohydrate chains of human chorionic gonadotropin. Effects on biological activity and receptor binding. AB - The effects of altered terminal sequences in human chorionic gonadotropin (hCG) N and O-linked glycans on receptor binding and signal transduction were analyzed using forms of hCG with remodelled carbohydrate chains. hCG derivatives were obtained by enzymic removal of the alpha 3-linked sialic acid residues followed by alpha 6-sialylation, alpha 3-galactosylation or alpha 3-fucosylation of uncovered Gal beta 1-->4GlcNAc (LacNAc) termini, or alpha 3-sialylation of Gal beta 1-->3GalNAc sequences. Also a form that carried GalNAc beta 1-->4-GlcNAc units, which are typical for pituitary hormone oligosaccharides, was derived by enzymic desialylation and degalactosylation followed by beta 4-N acetylgalactosaminylation. The potency to stimulate testosterone production and the binding to the lutotropin/choriogonadotropin receptor of the preparations were compared with those of native and desialylated hCG (as-hCG). The decrease in bioactivity caused by desialylation of hCG was only restored upon alpha 6 sialylation of the Gal beta 1-->4GlcNAc beta 1-->-2Man alpha 1-->3Man branch of the N-linked glycans. This was without a major effect on receptor binding. Further alpha 6-sialylation, occurring at the Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->6Man branch, resulted in a bioactivity below a level found with as-hCG, concomitant with a decreased receptor binding affinity. Similarly alpha 3 galactosylation of the Gal beta 1-->4GlcNAc beta 1-->2-Man alpha 1-->6Man branch yielded a hCG derivative that showed decreased bioactivity and receptor binding. alpha 3-Fucosylation of native as well as as-hCG also led to a decreased activity. Re-alpha 3-sialylation of the O-linked chains on as-hCG had little effect on the bioactivity and receptor binding. Hormone preparations with GalNAc beta 1-->4GlcNAc termini showed lower bioactivity and receptor affinity than as hCG. It is concluded that the Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->3Man- rather than the Gal beta 1-->4GlcNAc beta 1-->2-Man alpha 1-->6Man branch of the N-linked glycans on hCG plays an essential role in signal transduction, whereas the latter branch can potentially interfere with receptor binding. Furthermore attachment of sialic acid, but not of other sugars, to the first branch fulfils the requirement for the full expression of bioactivity, while sialylation of the O-linked chains is of minor importance. PMID- 7867651 TI - 3-Deoxy-octulosonic-acid-containing hexasaccharide fragment of unusual core type isolated from Hafnia alvei 2 lipopolysaccharide. AB - The hexasaccharide containing 3-deoxy-octulosonic acid (Kdo) was isolated from the carbohydrate material obtained after the mild acid hydrolysis of lipopolysaccharide of Hafnia alvei strain 2. The hexasaccharide was purified by gel filtration on Bio-Gel P-4 and P-2 columns. On the basis of sugar and methylation analyses, one- and two-dimensional NMR spectroscopic methods, the hexasaccharide was identified as [formula: see text] The tetrasaccharide linked to position 7 of Kdo is also part of the sialic-acid-containing O-specific unit. Di-substitution of Kdo at positions 7 and 8 has not been previously reported. PMID- 7867652 TI - An unusual polar lipid from the cell membrane of Mycoplasma fermentans. AB - The major unidentified polar lipid (compound X), recently demonstrated in the cell membrane of Mycoplasma fermentans, was purified by preparative silicic acid column chromatography. Chemical analyses of acid-hydrolyzed compound X revealed that, in addition to fatty acids, it contains glycerol, choline and phosphate in a molar ratio of approximately 1:1:2, and an amino acid that has a retention time similar to that of homoserine. The methylated fatty acid fraction of compound X was subjected to gas-liquid chromatography and revealed methyl palmitate and methyl stearate in a 4.6:1 molar ratio. The structure of compound X was further analyzed by combining mass spectrometry, 31P-NMR and 1H-NMR. The positive and negative fast atom bombardment spectra showed a major component of M(r) 1048 and a minor component of M(r) 1076. Two different phosphate groups were identified in each of the components by 31P-NMR. Fast atom bombardment, tandem mass spectrometry, negative and positive chemical ionization mass spectrometry together with mass spectra analyses of the water-soluble and ether-soluble products obtained by methanolysis has shown that, in addition to palmitic and stearic acid residues, the presence of glycerol, ribitol, cholinephosphate and homoserinephosphate residues. It is suggested that the apparent structure of compound X is either a phosphatidylcholine attached via a phosphotriester bond to a ribitolphosphohomoserine moiety or a phosphatidylhomoserine attached via a phosphotriester bond to a ribitolphosphocholine moiety. The major molecular species is the dipalmitoylderivative (M(r) 1048), whereas the minor molecular species is a stearoyl palmitoyl derivative (M(r) 1076). PMID- 7867654 TI - Human diseases with defects in oxidative phosphorylation. 1. Decreased amounts of assembled oxidative phosphorylation complexes in mitochondrial encephalomyopathies. AB - The amount of oxidative phosphorylation enzymes in mitochondrial encephalomyopathy patients has been studied by two-dimensional electrophoresis (blue native PAGE/Tricine-SDS-PAGE). Only 20 mg muscle was required to identify and analyse complexes I, III, IV, and V after Coomassie staining. In most cases reduced amounts of the involved complex(es) correlated well with decreased enzyme activities. The reliability of the method was reflected by the constant mutual ratio of the complexes found in all controls. Deviations from normal ratios were found to be more sensitive indicators for a defect than the absolute quantities, which varied considerably within the control group both in the enzymic and in the electrophoretic analysis. The effect of the mitochondrial tRNA(Leu(UUR)) mutation in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes on the amount of oxidative phosphorylation complexes was demonstrated for the first time directly on the protein level. In patients without known DNA mutations, specific defects of single complexes were identified. The new technique is a sensitive method for the identification of oxidative phosphorylation defects, complementary to enzymic measurements. PMID- 7867655 TI - Human diseases with defects in oxidative phosphorylation. 2. F1F0 ATP-synthase defects in Alzheimer disease revealed by blue native polyacrylamide gel electrophoresis. AB - F1F0 ATP-synthase (complex V) deficiencies in Alzheimer's disease are reported. Tissue specimens from the hippocampus of brains from patients with Alzheimer's disease were screened by blue native electrophoresis for alterations of the proteins of oxidative phosphorylation. Ubiquinol:cytochrome-c reductase (complex III) and cytochrome-c oxidase (complex IV) were found to be present at almost normal concentrations, however, complex V was substantially reduced in most cases studied. The specific reduction of complex V and the absence of electrophoretically detectable degradation products do not exclude a secondary defect of complex V, but should stimulate the search for genetic defects related to protein subunits of complex V. PMID- 7867653 TI - Studies on a stabilisation of ubisemiquinone by Escherichia coli quinol oxidase, cytochrome bo. AB - The Escherichia coli quinol oxidase, cytochrome bo, is closely related to the cytochrome c oxidase, cytochrome aa3 in all aspects of its structure and function except for the replacement of the cytochrome-c-binding site and its attendant CuA prosthetic group with a quinone-binding site. The putative oxidation of quinol by ferrihaem (cytochrome b) at this site in sequential one-electron steps requires the stabilisation of semiquinone. We have observed, by electron paramagnetic resonance, the properties of a ubisemiquinone radical in appropriately poised samples of purified enzyme reconstituted with excess ubiquinone. The ubisemiquinone is highly stabilised with respect to free ubisemiquinone; significant free radical can be observed even at pH 7.0, while at pH 9.0 the stability constant is 5-10. The pH dependence of the stability constant indicates that the anionic form of the semiquinone predominates above pH 7.5. The two electron couple has an Em7 of approximately 70 mV. Below pH 9, the pH dependence of the two-electron couple is -60mV/pH, indicative of a 2H+/2e- reaction. The line width of the EPR spectrum is approximately 0.9 mT, which is consistent with a ubisemiquinone anion. In comparison with other respiratory chain Q.- species that have been described, the relaxation rate in the presence of reduced haems appears comparable to magnetically isolated Q.- radicals. Partially resolved splittings of approximately 0.4 mT can be observed in the spectrum of Q.-bo (QH.bo). PMID- 7867656 TI - cDNA sequence and structure of a gene encoding trout testis high-mobility-group-1 protein. PMID- 7867657 TI - 1st International Meeting on the Scientific Basis of Modern Pharmacy. Athens, Greece, June 8-11, 1994. PMID- 7867658 TI - Design of histamine H3-receptor agonists and antagonists. AB - The development of highly potent and selective ligands for the characterization of histamine H3-receptors is reviewed. In the field of agonists stereoselectively methylated derivatives of the natural ligand are found to have the desired pharmacodynamic properties. Pharmacokinetic properties could be improved by forming bioreversible azomethine prodrugs of the primary amine with benzophenone derivatives. In the antagonist field a number of new leads belonging to different chemical classes are discovered. Potential compounds for drug development are identified. The radiolabelled probe [125I]iodoproxyfan shows high potency and selectivity in functional and binding studies. It is a useful compound for binding assays as well as for the detection and localization of histamine H3 receptors. PMID- 7867659 TI - Medicinal chemistry of muscarinic agonists for the treatment of dementia disorders. AB - Alzheimer disease (AD) is a neurodegenerative disorder lacking an effective therapy. The etiology is controversial and among different drug strategies, the cholinergic approach has gained great interest owing to biochemical and pharmacological evidence of the crucial role of acetylcholine in cognitive functions. Several attempts exploiting the boosting of the cholinergic system are currently under way. Inhibitors of the acetylcholinesterase enzyme sustain the availability of the natural transmitter by limiting its removal from the synapse. In a different approach, exogenous agonists may substitute acetylcholine itself. In this way the issue of the extensive cholinergic cell loss occurring in AD and leading to a reduction of cholinergic functions, could be advantageously bypassed. Moreover the discovery of different muscarinic receptor subtypes, most notably the M1 subtype as that involved in the postsynaptic transmission, has offered new opportunities to face the problem in a very specific way. In this line of research, we have now identified BIMC 182 as a new functionally selective M1 agonist. Whereas its affinity for the different receptor subtypes is almost similar (radioreceptor binding), its functional selectivity is pointed out by specific "in vitro" models. BIMC 182 behaves as a full agonist at M1 (rat superior cervical ganglion, pD2 4.8) and as a partial agonist at M2 and M3 sites (g.p. heart pD2 = 5.4 and g.p. ileum pD2 = 4.5). The agonist profile is further confirmed in hm1 transfected CHO cells where the compound stimulates PI turnover. BIMC 182 penetrates well the brain as shown by the increase in the energy of the low frequency band (theta waves) in the cortical EEG of rabbits (3 mg/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867660 TI - The design of potential antidiabetic drugs: experimental investigation of a number of beta-D-glucose analogue inhibitors of glycogen phosphorylase. AB - alpha-D-glucose is a weak inhibitor (Ki = 1.7 mM) of glycogen phosphorylase (GP) and acts as physiological regulator of hepatic glycogen metabolism; it binds to GP at the catalytic site and stabilizes the inactive T state of the enzyme promoting the action of protein phosphatase 1 and stimulating glycogen synthase. The three-dimensional structures of T state rabbit muscle GPb and the GPb-alpha-D glucose complex have been exploited in the design of better regulators of GP that could shift the balance between glycogen synthesis and glycogen degradation in favour of the former. Close examination of the catalytic site with alpha-D glucose bound shows that there is an empty pocket adjacent to the beta-1-C position. beta-D-glucose is a poorer inhibitor (Ki = 7.4 mM) than alpha-D glucose, but mutarotation has prevented the binding of beta-D-glucose in T state GP crystals. A series of beta-D-glucose analogues has been designed and tested in kinetic and crystallographic experiments. Several compounds have been discovered that have an increased affinity for GP than the parent compound. PMID- 7867661 TI - Design of drugs through a consideration of drug metabolism and pharmacokinetics. AB - Drug metabolism input to the discovery process has been to date largely on an empirical case by case basis. Considerable advances have been made, such that basic rules can be applied to the behaviour of a compound in man based on physico chemistry and structure. This is particularly true in the area of the cytochrome P-450 enzymes, the principal enzymes involved in the primary clearance of drugs. The major human forms, CYP2D6, CYP2C9 and CYP3A4 all have distinct substrate preferences which are being catalogued and rationalised. Such understandings will not only impact on existing drugs. Since the enzymes and systems will remain the same, these understandings can be applied to the design of molecules for the targets of the future, whilst the structure activity relationships of those targets are being researched and revealed. PMID- 7867662 TI - The metabolism of drugs by the gut flora. AB - Gut flora and gut contents can be considered as a system with huge metabolic capacity, qualitatively and quantitatively different from the body cells and organs. That system changes along with life and nutrition, but despite broad investigation has not yet been defined satisfactorily. In many cases inter individual and intra individual differences in drug metabolism could be linked to variations in the gut flora metabolism. Gut flora metabolism of drugs and other xenobiotic metabolites excreted in bile is the key phase responsible for enterohepatic circulation. In the last decade there has been more and more evidence for the crucial role of the gut flora cysteine conjugate beta-lyase in the metabolism of cysteine conjugates. A new pathway for paracetamol cysteine conjugate metabolism has been directly linked with gut flora activity, as demonstrated in our studies. Nowadays, it is quite clear that gut flora metabolism must be considered an integral part of drug metabolism and toxicity studies. PMID- 7867663 TI - The metabolism of alicyclic amines to reactive iminium ion intermediates. AB - The evidence implicating the formation of iminium ions as reactive intermediates in the metabolism of alicyclic amines has been reviewed. The mechanism of formation of iminium ions and their conversion to alpha-carbonyl compounds or demethylated amines is discussed. The use of a simple cyanide trapping technique for iminium ions has been demonstrated to monitor a large number of alicyclic drugs for iminium ion formation. The possible role of iminium ions in the pharmacology and toxicology of alicyclic amines is considered. PMID- 7867664 TI - Molecular toxicology of peroxisome proliferators. AB - The rat Reuber hepatoma cell cell line, H4IIEC3, has been used in gene transfection studies to study the molecular mechanisms of induction of the acyl CoA oxidase gene, the first and rate-limiting enzyme of the peroxisomal fatty acid beta-oxidation spiral. cDNAs encoding the peroxisome proliferator activated receptor and the 9-cis retinoic acid receptor were transfected into the cells, either in the presence or absence of their cognate ligands (Wy-14,643 and 9-cis retinoic acid respectively), in addition to the acyl CoA oxides promoter linked to a chloramphenicol acetyltransferase reporter gene construct. The above experimental approach has confirmed that the 9-cis retinoic acid receptor acts cooperatively with the peroxisome receptor in mediating activation of the acyl CoA oxidase gene. In addition, in vivo experiments have demonstrated that treatment of rats with peroxisome proliferators substantially increase the hepatic levels of the peroxisome receptor mRNA itself. Taken collectively, the above data provides a wealth of molecular and mechanistic information on perioxisome proliferation in the rat and is discussed in terms of the safety assessment of peroxisome proliferators in man. PMID- 7867665 TI - The use of computers in the safety evaluation of drugs and other chemicals. AB - The toxicity and carcinogenicity of drugs and other chemicals is, in most cases, mediated by highly reactive intermediates which are generated following metabolism catalysed by the enzymic apparatus of the exposed organisms. These reactive intermediates readily interact covalently with vital cellular components to provoke toxicity and carcinogenicity. The ubiquitous cytochrome P450-dependent mixed-function oxidases are the most important enzyme system in the activation of chemicals. This enzyme system comprises a number of families, each of which contains one or more subfamilies. The CYPIA and CYP2E subfamilies are the most closely associated with the production of reactive intermediates and, consequently, the manifestation of toxicity and carcinogenicity. A computer based molecular structure procedure (COMPACT) has been developed which, via a calculation of the molecular and electronic structure of the chemical, determines whether the chemical will interact with either of these two cytochrome P450 subfamilies and hence be metabolised to form reactive intermediates that manifest toxicity. As the basal levels of these two subfamilies are generally low, the ability of a chemical to induce them selectively, on repeated administration, is an important determinant of its toxic and carcinogenic potential. This inductive capability may be determined in short-term studies (ENACT) using only a small number of animals. Thus the combination of COMPACT and ENACT provides a rapid and inexpensive means for the preliminary screening of chemicals for toxicity and carcinogenicity before undertaking the long-term and expensive rodent lifetime bioassays. PMID- 7867666 TI - Capillary electrophoresis and capillary electrophoresis-mass spectrometry in drug and metabolite analysis. AB - The structural diversity of modern therapeutic agents can lead to labour intensive method development for each drug and the structural characterization of their metabolites. In this work, we show the benefits of the high resolution capabilities of capillary electrophoresis (CE) and demonstrate that nonaqueous CE and on-line CE-mass spectrometry (CE-MS) leads to enhanced resolution and recovery of mixtures containing the prototype H2-antagonist, mifentidine, and putative metabolites. Furthermore, the usefulness of CE-tandem MS (CE-MS/MS) is also demonstrated by the structural characterization of the novel N2 hydroxylamine metabolite of mifentidine. PMID- 7867668 TI - Drug targeting with nanoparticles. AB - Nanoparticles are colloidal polymeric particles (size < 1000 nm) to which drugs are bound by sorption, incorporation, or chemical binding. After intravenous injection they normally distribute into the organs of the reticuloendothelial system (liver, spleen, lungs, bone marrow). However, their body distribution can be altered by coating with surfactants or with physiological components such as serum complement factors. The influence of these coatings on the body distribution and possible mechanisms for the alteration of this distribution are discussed. Differently coated nanoparticles can be used for the targeting of bound drugs to tumors, to the brain, and to inflamed areas in the body. PMID- 7867667 TI - Enantiospecific analysis: applications in bioanalysis and metabolism. AB - Enantiospecific analysis has a significant role in modern drug development from discovery-chemistry to the clinical evaluation of novel compounds. Chromatographic techniques, involving the use of either chiral derivatizing agents or chiral stationary phases, represent the most commonly used approaches to enantiospecific analysis. The advantages and limitations of these two techniques are examined using the analysis of the enantiomers of the 2 arylpropionic acids (tiaprofenic acid and ibuprofen) and the chiral N-oxides of N ethyl-N-methylaniline and pargyline, as representative examples for each approach. The potential of biosensors in enantiospecific analysis is addressed and some preliminary results on the development of an enantioselective biosensor for the analysis of (S)-warfarin are presented. PMID- 7867669 TI - Surfactant systems: microemulsions and vesicles as vehicles for drug delivery. AB - Although surfactants have been widely used as pharmaceutical adjuvants for many years, it is only relatively recently that their phase structures have been seriously considered as drug delivery vehicles per se. This review highlights the work to date investigating the potential of microemulsions as drug carriers and also reports on preliminary studies performed on the use of vesicles formed from nonionic surfactants. PMID- 7867670 TI - Bioequivalency evaluation by comparison of in vitro dissolution and in vivo absorption using reference equations. AB - Using in vitro dissolution and in vivo absorption of different generics or batches for an appropriate drug and dosage form, a reference equation of form: ka = a+bkd+dkd2 can be proposed. In the case of availability of standardised in vitro-in vivo data for a specific drug, a Level A a correlation of this type containing experimentally determined a, b, d parameters would serve to predict in vivo absorption phase of the drug. The larger number of batches, the stronger will be the predictive power of these parameters. PMID- 7867671 TI - Plasma levels and therapeutic response: the relevance to community pharmacy. AB - An assessment of 26 patients, taking theophylline for COAD or asthma, was undertaken in a Belfast Community pharmacy. Patients had peak flow rate and serum theophylline concentration monitored. Based on these findings patients were counselled and, where appropriate, theophylline dosage was adjusted using a pharmacokinetic computer program. A statistically significant improvement was found between the number of patients who had a serum theophylline concentration in the therapeutic range at the initial assessment and at 3 months and 12 months. This was accompanied by a statistically significant improvement in peak expiratory flow rates. PMID- 7867672 TI - Are we doing too many animal biodisposition investigations before phase I studies in man? A re-evaluation of the timing and extent of ADME studies. AB - This commentary attempts to re-evaluate, from a scientific standpoint, the timing and usefulness of undertaking detailed kinetic and metabolic studies in many animals from several species, and extrapolating the findings to man. This reappraisal is now possible due to the conditional acceptance of harmonised guidelines on toxicokinetics at ICH2 in Orlando in 1993, the results from which can provide much of the information that is required to design and validate safety studies and to extrapolate exposure or safety margins to man. PMID- 7867673 TI - General practitioners for rational use of drugs. Examples from Sweden. AB - In the south west region of Stockholm a group of 125 general practitioners (GPs) at 27 health centres asked about the extent to which the drug formulary of the University Hospital was useful in their practices. To answer this question, the GPs asked their local pharmacies for prescribing data. When presented this started a process towards rational prescribing from within the group of GPs, including repeated prescribing surveys, starting with health centres as the unit of analysis and proceeding to individual prescribing analyses on request by the GPs. As the prescribing data revealed major differences between health centres, the GPs arranged two workshops on drug use in primary health care. They developed a list of 167 recommended drugs based on drug statistics and morbidity in general practice. Signs of increased cost cautiousness could be shown. There was a clear trend towards both smaller volumes and cost per prescription item for the health centres in the study area. Compared to the national prescribing pattern, prescribing practice in the study area represented a 20 per cent lower drug cost. Although the GPs decided on a drug list separate from that of the hospital, collaboration between the Drug and Therapeutic Committee at the hospital and the GPs increased as a result of their increased engagement in drug management, thereby also bridging the gap between primary health care and clinical pharmacology. PMID- 7867674 TI - CYP2D6 genotype determination in the Danish population. AB - CYP2D6 genotyping was carried out by XbaI restriction fragment length polymorphism analysis and polymerase chain reaction in 168 healthy Danish volunteers, 77 extensive metabolizers (EM) and 91 poor metabolizers (PM) of sparteine. All EM were genotyped correctly as heterozygous or homozygous for the functional (wild type) gene, D6-wt. However, the D6-wt gene was apparently also present in 11 (12%) of the PM who accordingly were incorrectly genotyped as EM. The specificity of genotyping PM thus was 100% but the sensitivity was only 88%. The most common allele was the D6-wt with an apparent frequency of 0.741 (0.026) in the Danish population and the second most common allele was the D6-B with an apparent frequency of 0.194 (0.024). The median (range) of the sparteine metabolic ratio (MR) in 47 homozygous D6-wt EM was 0.28 (0.11-4.10) and the corresponding value in heterozygous EM was 0.36 (0.11-9.10). The median difference was 0.09 (95% confidence interval: 0.02-0.16). CYP2D6 phenotyping is a promising tool in tailoring the individual dose of tricyclic antidepressants, some neuroleplics and some antiarrhythmics. However if the genotype test could be improved with regard to both sensitivity in PM and the ability to predict CYP2D6 activity in EM then it would be of even greater clinical value in therapeutic drug monitoring. PMID- 7867675 TI - Effect of BAY x 7195, an oral receptor antagonist of cysteinyl-leukotrienes, on leukotriene D4-induced bronchoconstriction in normal volunteers. AB - Leukotrienes (LT) have been proposed to play an important role in the pathogenesis of asthma. This paper reports the results of two studies investigating the effect of BAY x 7195, a new oral receptor antagonist of cysteinyl-leukotrienes, on LTD4-induced bronchoconstriction in healthy male volunteers. Using a double-blind, placebo-controlled, crossover design, volunteers received 250 mg (n = 6; study 1) and 100 and 500 mg (n = 6; study 2) of BAY x 7195. Bronchoprovocation with nebulized LTD4 was performed 2 (250 mg) and 2 and 8 (100 and 500 mg) h p.a. The specific airway's conductance (SGaw) was used to assess the airway's response. Blood samples to determine plasma concentrations of BAY x 7195 were taken at the end of bronchoprovocation. BAY x 7195 showed no effect on baseline lung function. Compared to placebo, the different doses of BAY x 7195 increased the concentration of LTD4 needed to produce a 35% decrease in SGaw 2 h p.a. between 1- and 23-fold. Eight hours p.a., 100 and 500 mg caused shifts in the concentration-response curve of between 1- and 13-fold. There was no predictive relationship between plasma concentrations of BAY x 7195 and the response to LTD4 challenge. However, there was a relationship between dose and effect. No relevant adverse effects were reported. In conclusion, the present results suggest that BAY x 7195 is an effective LTD4 receptor antagonist in man. PMID- 7867676 TI - Angiotensin II receptor blockade with single doses of valsartan in healthy, normotensive subjects. AB - Valsartan (CGP 48933), a specific blocker of the angiotensin II (Ang II) receptor subtype 1 (AT1 receptor) was administered in single, oral doses of 40 mg and 80 mg to six healthy, normotensive male volunteers in a double-blind, placebo controlled, randomized crossover trial. The aims of the study were a) to assess the extent, time course and dose-dependency of inhibition of the pressor effect of exogenous Ang II; and b) to attempt to correlate AT1 receptor blockade with the drug levels in plasma and with other markers of biological activity of the trial drug such as plasma renin activity (PRA). Using the Finapres device and i.v. bolus injections of exogenous Ang II, AT1 receptor blockade was assessed by measuring blood pressure (BP) and heart rate (HR) on a beat-by-beat basis. A dose response curve for Ang II was obtained for each subject before and at 2, 4, 6, 8 and 24 h after administration of placebo and of the two doses of valsartan. PRA was measured with a conventional radioimmunoassay method. Data evaluation included a) descriptive analysis of the changes of the Ang II dose-response curves after valsartan, as compared to the curve on placebo; b) calculation of the pressor dose D30 of Ang II at each time-point, using linear regression; c) assessment of the effect of 4 micrograms Ang II on systolic BP and HR and the calculation of the percentage inhibition of these effects after valsartan; d) description of the relationship between drug levels in plasma and the measures of AT1 blockade, including pharmacokinetic-pharmacodynamic modeling with an Emax model for the percentage inhibition of systolic BP and HR.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7867677 TI - Acute and chronic effects of a new low molecular weight dermatan sulphate (Desmin 370) on blood coagulation and fibrinolysis in healthy subjects. AB - The acute and chronic effects on blood coagulation and fibrinolysis of a new molecular weight dermatan sulphate (Desmin 370) have been investigated in a double blind, placebo-controlled cross over study in 12 healthy volunteers. The compound (100 and 200 mg) was injected IM and the expected heparin cofactor II potentiating effect, reflecting dermatan sulphate activity, peaked after 2 h and was still detectable after 9 h. Surprisingly for this type of compound, a substantial increase in anti-Xa activity also appeared and lasted up to 12 h in the absence of a significant change in aPTT. The bovine-thrombin time was not changed, while human-thrombin times were slightly, albeit non-significantly, prolonged. The activity of t-PA was increased 6h after the higher dose, but the overall pattern of fibrinolytic activities did not suggest any important change after drug treatment in comparison to placebo. No residual or cumulative effect on any of the investigated parameters was detectable 24 h after the injection on the 4th and 8th days during repeated daily administration. Parallel in vitro and in vivo investigations showed that the unexpected anti-Xa effect was not attributable to contamination by traces of low molecular weight heparin. Desmin 370, a low molecular weight dermatan sulphate that potentiates heparin cofactor II and also inhibits Factor Xa, deserves clinical evaluation as an antithrombotic agent. PMID- 7867678 TI - Effects of mizolastine and clemastine on actual driving and psychomotor performance in healthy volunteers. AB - The acute effect of doses of mizolastine 5, 10, 20 and 40 mg, an active control (clemastine 2 mg) and placebo on actual car driving and psychomotor performance have been compared. Twenty four healthy volunteers were treated according to a double-blind, 6-way cross-over design. In the driving test, lasting about 1 h, lateral position control and speed were continuously measured; the psychomotor test battery, lasting 50 min, comprised critical flicker-fusion frequency, critical instability tracking, divided attention, memory search and choice reaction time, and vigilance studies; and mood changes and possible adverse effects were rated on visual analogue scales. The results showed a dose-response relationship: mizolastine 40 and 20 mg impaired driving and psychomotor performance. The effect of mizolastine 40 mg on driving was strongly correlated with that of clemastine (r = 0.78) and was comparable to the effect of a blood ethanol level of 0.8 mg.ml-1. Mizolastine 5 mg and 10 mg did not have a significant effect on driving performance and psychomotor tests. It was concluded that at a 10 mg dose of mizolastine, the therapeutic dose, it could be considered a safe anti-histamine, although individual adverse reactions cannot be completely ruled out. PMID- 7867679 TI - Acrivastine, terfenadine and diphenhydramine effects on driving performance as a function of dose and time after dosing. AB - The study was conducted according to a nine-way, observer- and subject-blind, cross-over design. Its purpose was to compare the single-dose effects of the following drugs on driving performance: acrivastine (8, 16 and 24 mg); the combination of acrivastine (8 mg) with pseudoephedrine (60 mg); terfenadine (60, 120 and 180 mg); diphenhydramine-HCl (50 mg); and placebo. The subjects were 18 healthy female volunteers. Drug effects were assessed in two repetitions of two driving tests (highway driving and car-following) after each treatment. Acrivastine's impairing effects in both driving tests were similarly dose related. The 8-mg dose had a small, but significant, effect on highway driving in the first trial. The 16-mg and 24-mg doses significantly impaired driving in both tests during the first trial and the 24-mg dose did so again during the second trial. Neither the combination of acrivastine with pseudoephedrine nor terfenadine caused any significant impairment of performance. Diphenhydramine significantly impaired driving in both tests during every trial. In conclusion, the normal therapeutic dose of acrivastine (8 mg) had little effect on driving performance, and virtually none when that dose was given in combination with pseudoephedrine (60 mg). Higher doses of acrivastine severely impaired driving performance. Terfenadine had no significant effect on driving performance after any dose while diphenhydramine strongly impaired every important driving parameter. PMID- 7867680 TI - Haemodynamic dose-efficacy of levosimendan in healthy volunteers. AB - Levosimendan is a new calcium-sensitiser intended for the treatment of congestive heart failure. The results of preclinical studies indicate it has positive inotropic and vasodilator effects. In the open study reported here up to 5 mg levosimendan and vehicle were administered to 8 healthy male volunteers at one- to 2-week intervals. Efficacy was evaluated using M-mode echocardiography, and by measuring systolic time intervals, recording ECG and measuring blood pressure. For almost all haemodynamic parameters except heart rate (HR) the maximum effect was seen 10 or 20 min after drug infusion. Effects 10 min after infusion of drug and vehicle were compared. HR was significantly increased 10 min only after infusion of 5 mg: significant increases were seen 60 min after infusions of 2, 3 and 5 mg (4, 8 and 17 beats.min-1, respectively). Diastolic blood pressure was significantly lower after doses of 1 mg or more. The decrease after 5 mg was 17 mmHg. Systolic blood pressure tended to increase. Fractional shortening (FS) and ejection fraction (EF) increased significantly after doses of 1 mg and higher. EF 10 min after infusion of vehicle was 54%. It increased to 73% after 5 mg. Decreases in electromechanical systole (QS2i) 10 min after 2, 3 and 5 mg were significant. There were no clinically significant adverse events or changes in laboratory safety values. The changes in QS2i, FS, EF and blood pressure indicate that levosimendan has positive inotropic and vasodilator effects in healthy subjects. PMID- 7867681 TI - Pharmacokinetic and pharmacodynamic studies following single and multiple doses of rolafagrel, a novel inhibitor of thromboxane synthase, in normal volunteers. AB - The pharmacokinetics and pharmacodynamics of rolafagrel (FCE 22178), a novel thromboxane synthase inhibitor, were evaluated after single and multiple oral doses in eight healthy volunteers. After a single dose (400 mg), the drug was absorbed rapidly, peak plasma concentrations being attained within 2 h in all subjects. Elimination followed a biphasic course, with a rapid initial decline followed after 12-24 h by a late phase with a terminal half-life of about 10 h. About 100% of the administered dose could be recovered in urine within 72 h, mostly in conjugated form. During multiple dosing (400 mg t.i.d. for 5 days), steady-state conditions were approached on day 2 and AUC values over a dosing interval were similar to those observed after a single dose (72.3 vs 76.3 micrograms.ml-1.h). Pharmacokinetic parameters calculated after multiple doses were similar to those observed after a single dose (Cmax: 20.1 vs 18.2 micrograms.ml-1; tmax: 1.2 vs 1.1 h; terminal half-life: 10.9 vs 11.4 h; CL: 85.2 vs 70.4 ml.h-1.kg-1; V: 1.23 vs 1.24 l.kg-1). Platelet generation of thromboxane B2, the stable breakdown product of thromboxane A2, was inhibited by 85% at a plasma rolafagrel concentration of about 4 micrograms.ml-1, and only a small increase in inhibition was observed at higher concentrations. PMID- 7867682 TI - Pravastatin has no direct effect on transmembrane cationic transport systems in human erythrocytes and platelets. AB - In vitro incubation of human erythrocytes and platelets with the 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitor pravastatin in the concentration range 1 nM to 10 microM did not affect the activity of the Na(+)-K(+)-pump, Na(+) K(+)-cotransport or Na(+)-Li(+)-countertransport, or the ground membrane leak for Na+ and K+. The data indicate that pravastatin has no direct effect on transmembrane cationic transport systems in red blood cells or platelets. PMID- 7867683 TI - Pharmacokinetic interaction study between benazepril and amlodipine in healthy subjects. AB - Pharmacokinetic interaction between benazepril (ACE inhibitor) and amlodipine (calcium channel blocker) was studied in 12 healthy subjects. Single doses of benazepril hydrochloride (10-mg tablet) and amlodipine besylate (tablet equivalent to 5 mg amlodipine) were administered alone or in combination according to a three-way, Latin-Square, randomized cross-over design. Serial blood samples were collected following each administration for the determination of benazepril and its active metabolite benazeprilat and amlodipine. The mean values of AUC (0-4 h), Cmax and Tmax for benazepril given as combination versus given alone were 161 vs 140 ng.h.ml-1, 168 vs 149 ng.ml-1, and 0.5 vs 0.6 h. The mean values of AUC (0-24 h), Cmax and Tmax for benazeprilat after benazepril given as combination versus given alone were 1470 vs 1410 ng.h.ml-1, 292 vs 257 ng.ml-1, and 1.7 vs 1.5 h. The mean values of AUC (0-144 h), Cmax and Tmax for amlodipine given as combination versus given alone were 118 vs 114 ng.h.ml-1, 2.5 vs 2.3 ng.ml-1, and 8.3 vs 9.0 h. The differences in these pharmacokinetic parameters between the combination and monotherapy treatments were not statistically significant based on ANOVA. The results of this study indicate that no pharmacokinetic interaction existed between the two drugs. PMID- 7867684 TI - Elimination of fluconazole during continuous veno-venous haemodialysis (CVVHD) in a single patient. PMID- 7867685 TI - Nitrate, nitrite and N-nitroso compounds. AB - A risk assessment has been made on nitrate, nitrite and N-nitroso compounds encountered in the human diet. Vegetables constitute a major source of nitrate providing over 85% of the average daily human dietary intake. Nitrite and N nitroso compounds present in the diet contribute relatively small amounts to the body burden and the major source of these biologically reactive compounds is derived from the bacterial and mammalian metabolism of ingested nitrate. Additionally, endogenous synthesis provides an important source contributing to the body burden of nitrate. Data from animal toxicological studies, human effects and epidemiological surveys have been reviewed and evaluated. It is concluded that there is no firm scientific evidence at present to recommend drastic reductions beyond the average levels of nitrate encountered in vegetables grown in keeping with good agricultural practice. Recommendations have also been made for further animal and human studies to be carried out to elucidate the potential risks to man from ingested nitrate. PMID- 7867686 TI - Effect of amiloride on inotropic and toxic actions of ouabain in guinea-pig left atria. AB - The effect of amiloride on the positive inotropic and toxic effects of ouabain in guinea-pig left atria has been studied. In atria driven at 1 Hz, amiloride (0.3 and 0.5 mM) decreased the EC50 but did not affect the maximal tension developed by ouabain. At 0.1 Hz, amiloride did not change either the EC50 or the maximal tension developed by ouabain. Ouabain toxicity (onset of arrhythmias) was not changed by amiloride at either frequency of stimulation. Therefore, amiloride did not antagonize either the positive inotropic or the toxic effect of ouabain. The positive inotropic effect of amiloride has been ascribed to the inhibition of the Na+/Ca2+ exchanger. Since amiloride inhibits also the Na+/H+ exchanger, 5-(N ethyl-N-isopropyl)amiloride (EIPA), an amiloride derivative which selectively inhibits the Na+/H+ exchange, has been tested to evaluate the role of the Na+/H+ exchange in the amiloride-ouabain interaction. EIPA increased the EC50 values of ouabain and decreased the maximal developed tension by the glycoside in atria driven at 0.1 and 1 Hz, but did not antagonize the toxic response (arrhythmias) of atria to ouabain. It is suggested that the inhibition of Ca2+ exit through the Na+/Ca2+ exchange by amiloride and ouabain may explain the observation that the positive inotropic effects of amiloride and ouabain are additive. PMID- 7867687 TI - Release of endogenous ATP from the caudal artery in rats with arteriosclerosis. AB - Noradrenaline significantly increased (by a prazosin-sensitive mechanism) the overflow of ATP and its metabolites from the caudal arteries of rats treated with excess vitamin D2 and a high-cholesterol diet (arteriosclerotic rats), although the amount of the overflow was smaller than that in the normal rats. The arteries from the arteriosclerotic rats showed a marked increase in the calcium content and there was a significant negative correlation between the noradrenaline induced overflow of ATP and the arterial calcium content. These findings indicate that ATP release from arteriosclerotic rat caudal arteries mediated by alpha 1 adrenoceptors is impaired in proportion to the extent of arterial calcification. PMID- 7867688 TI - Cleland's reagents block lethal and hypnotic effects of pentobarbital. AB - We studied the effect of the reducing agents dithiothreitol and dithioerythritol (Cleland's reagents) on the hypnotic and toxic effects of pentobarbital in rodents. In pentobarbital anesthetized rats (50 mg/kg), the i.v. infusion of dithioerythritol (84 mumol/kg/min for 10 min) accelerated the return of eyeblink and righting reflexes (to 4 +/- 1 min vs. 22 +/- 2 min,k and 15 +/- 1 vs. 65 +/- 8 min respectively (P < 0.001). In mice receiving lethal doses of pentobarbital, the 4 h LD50 was 128 +/- 2 mg/kg; when dithioerythritol was given simultaneously, LD50 was > 165 mg/kg. Dithiothreitol also had a protective effect in rats. Oxidized dithiothreitol or dithioerythritol had no effect on pentobarbital sleeping time or mortality. The protective effect of dithioerythritol was dose dependent; a high dose (294 mg/kg) gave complete protection in the short term, but killed the mice subsequently. The study shows that Cleland's reagents or their derivatives can act as pentobarbital antagonists in rodents, although side effects limit that usefulness. It also suggests caution in the use of dithiothreitol and related compounds during pentobarbital anesthesia. PMID- 7867689 TI - Acute toluene exposure decreases extracellular gamma-aminobutyric acid in the globus pallidus but not in striatum: a microdialysis study in awake, freely moving rats. AB - Intracerebral brain microdialysis was performed in awake, freely moving rats to study the effect of acute inhalation exposure of toluene (2000 ppm, 2 h) on extracellular levels of gamma-aminobutyric acid (GABA) within the globus pallidus and the striatum. GABA within the globus pallidus decreased (20%) during and after (26%) exposure to toluene, while no reduction was seen in the striatal GABA level during exposure. After the exposure there was a tendency towards an increase (maximally 37%) in striatal GABA. 2 h of perfusion with tetrodotoxin (10(-6) M) decreased (32%) the extracellular GABA levels within the globus pallidus. The results suggest that the effect of acute toluene exposure varies with brain region and that the GABA output from the striatum to globus pallidus is more affected by the exposure than the GABA release within the striatum. PMID- 7867690 TI - Modification of hepatic cytochrome P450 profile by cocaine-induced hepatotoxicity in DBA/2 mouse. AB - Previous studies in our laboratory have shown that a hepatotoxic dose of cocaine increases coumarin 7-hydroxylase activity in male DBA/2 mouse liver. In the present study, the dose- and time-dependent responses of the hepatic CYP2A4/5 complex to cocaine-induced liver damage were studied. Cocaine increased CYP2A4/5 levels in a dose-dependent manner. The maximal increases in coumarin 7 hydroxylase activity (4-fold), microsomal CYP2A4/5 content (3-fold) and steady state mRNA levels (10-fold) were observed at 24 h after administration of a single dose of 60 mg/kg cocaine coinciding with morphologically detectable diffuse liver damage, while the total P450 content was not changed. 3 and 5 days after the daily administration of cocaine severe, mainly pericentral (zone III of Rappaport), liver damage was apparent in parallel with a clear decline in CYP2A4/5 mRNA, protein content and coumarin 7-hydroxylase activity. After 5 days of treatment, CYP2A5 still remained at a very low level but an induction in CYP2B10 protein and related pentoxyresorufin O-dealkylase activity was observed. No marked changes in microsomal CYP2Cx and CYP1A1/2 contents or associated activities were observed. Dimethylnitrosamine N-demethylase activity, a marker for CYP2E1, decreased in parallel with increased cocaine dose and time and the severity of liver damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867691 TI - Activation of aflatoxin B1 by mouse CYP2A enzymes and cytotoxicity in recombinant yeast cells. AB - The ability of three highly homologous mouse liver CYP2A enzymes to activate aflatoxin B1 was studied by expressing them in recombinant AH22 Saccharomyces cerevisiae yeast cells. The reconstituted monooxygenase complex with CYP2A5 purified from yeast cell microsomes produced epoxide at a rate of 17.2 nmol/min per nmol P450 in the presence of 50 microM aflatoxin B1 while CYP2A4 had about 10% and P4507 alpha only 1.5% of this activity. However, Km values were 530 and 10 microM and Vmax values 12.5 and 14.3 nmol/min per nmol P450 for CYP2A4 and CYP2A5, respectively. When recombinant yeast cells were exposed to aflatoxin B1 LC50 concentrations were 7.5 +/- 5.5 microM for CYP2A4, 0.45 +/- 0.10 microM for CYP2A5 and > 320 microM for P4507 alpha expressing yeast cells. Aflatoxin B1-DNA adduct levels in the same yeast cells were 50, 890 pmol/mg DNA and below detection limit when 3.0 microM aflatoxin B1 was used in the incubation mixture. Coumarin an inhibitor for CYP2A4 and a substrate for CYP2A5 diminished the toxicity of aflatoxin B1 in a dose-dependent manner for these recombinant yeast cells. These data demonstrate that (1) highly homologous mouse CYP2A enzymes activate aflatoxin B1 in a different manner and (2) that recombinant yeast cells expressing mammalian CYP enzymes are a useful and inexpensive system to test the role of different enzymes in aflatoxin B1 toxicity. The data also indicate that mouse CYP2A5 and its counterpart in other species could have a significant role in aflatoxin B1 toxicity in organs where it is expressed at high levels. PMID- 7867692 TI - In vivo administration of taurine and niacin modulate cyclophosphamide-induced lung injury. AB - The antiinflammatory, antioxidant activity of taurine and niacin against cyclophosphamide-induced early lung injury in rats was investigated. A single intraperitoneal injection of cyclophosphamide markedly altered the levels of several biomarkers in bronchoalveolar lavage fluid: total protein, albumin, angiotensin converting enzyme, lactate dehydrogenase, lactate, N-acetyl-beta-D glucosaminidase, alkaline phosphatase, acid phosphatase and lipid peroxidation product were significantly elevated. In contrast, decreased levels of total reduced glutathione (GSH) and ascorbic acid were observed. Cyclophosphamide significantly increased malondialdehyde levels in serum and lung. Significant increases in lung content of lipid hydroperoxides were seen that paralleled the decreased levels of total reduced glutathione and total sulfhydryl groups. Pretreatment of rats with daily intraperitoneal injection of taurine plus niacin 7 days prior to and 2 days after cyclophosphamide insult significantly inhibited the development of lung injury, prevented the alterations in lavage fluid biomarkers associated with inflammatory reactions, with less lipid peroxidation and restoration of antioxidants. In conclusion, our results suggest that taurine and niacin in combination is efficient in blunting cyclophosphamide-induced pulmonary damage. PMID- 7867693 TI - Assessment of myeloperoxidase activity in renal tissue after ischemia/reperfusion. AB - We have shown that a photometric assay of myeloperoxidase derived from rat blood polymorphonucleocytes employing 3,3',5,5'-tetramethylbenzidine as substrate is more sensitive than an established assay employing o-dianisidine. We went on to demonstrate that rat renal tissue is capable of inhibiting peroxidase activity. This activity approached 100% when the rat renal supernate was incubated at 60 degree C for 2 h and the assay was conducted in the presence of a 10-fold higher concentration of hydrogen peroxide (H2O2). Rat kidneys undergoing 45 min ischaemia and 1,3 and 6 h reperfusion in vivo, exhibited significant increases in myeloperoxidase activity, indicating tissue polymorphonucleocyte accumulation. Monoclonal antibodies against rat intercellular adhesion molecule 1 (ICAM-1) and CD18 of beta 2-integrins administered both 5 min before a period of 45 min renal ischaemia (20 micrograms/kg i.v.) and at the commencement of 1 h reperfusion (20 micrograms/kg i.v.) reduced renal tissue polymorphonucleocyte accumulation. However, similar treatment with the parent murine antibody immunoglobulin G1 (IgG1) and an unrelated murine antibody, IgG2a, also significantly reduced renal tissue polymorphonucleocyte accumulation. In conclusion, we demonstrate that the rat renal suppression of peroxidase activity can be overcome by a combination of heat inactivation and the provision of excess assay H2O2. In addition, the available evidence suggests that murine monoclonal antibodies against rat adhesion molecules may exert non-specific actions in our model of renal ischaemia/reperfusion in vivo. PMID- 7867694 TI - Effect of disulfiram administration on glutamate uptake by synaptosomes in the rat brain. AB - Although disulfiram used as a pharmacological agent in the treatment of alcoholism is reported to act on both peripheral and central nervous systems with several adverse effects, the neurotoxic property of the drug has not been properly elucidated. We observed that the chronic administration of the drug to rats significantly inhibited synaptosomal (Na+,K+)-ATPase and basal Mg(2+)-ATPase activities. Further, the uptake of gamma-aminobutyric acid and L-glutamate which rely on the energy provided by this system was depleted following chronic drug administration. Similar findings were observed when the isolated synaptosomes were treated with the drug in an in vitro system. Further, treatment of synaptosomes with ouabain, a known inhibitor of (Na+, K+)-ATPase resulted in significant depletion of 3H-GABA and L-[3H]glutamate uptake into synaptosomes indicating the importance of the enzyme in the uptake mechanism. However, diethyldithiocarbamate, a major metabolite of disulfiram did not elicit any change in either the enzyme activity or the uptake of these neurotransmitters. On the basis of these evidences, we suggest that the chronic disulfiram administration attenuated the neurotransmitter uptake mechanism and resulted in higher extracellular concentration of glutamate that could lead to glutamate induced neurotoxicity. PMID- 7867695 TI - Studies on the contracture inducing action of triphenyltin in the mouse diaphragm. AB - Triphenyltin induces a contracture of the mouse phrenic nerve-diaphragm preparation. This contracture was not inhibited by (+)-tubocurarine, high magnesium or the absence of electrical stimulation. Triphenyltin (0.1 mM) reduced the muscle membrane potential, the amplitude of the muscle action potential and the muscle membrane input resistance. Pretreatment with high K+ (25 mM) or veratridine (1.5 microM; a Na+ channel activator) briefly shortened the onset of the contracture and increased the peak tension of the contracture. Pretreatment with tetrodotoxin (0.3 microM; a Na+ channel blocker) or glycerol (a T tubule uncoupler) however, significantly reduced the triphenyltin-induced contracture. Removing Ca2+ from external solution and prolonged treatment with either caffeine (20 mM) or ryanodine (2 microM) inhibited the triphenyltin-induced contracture. However, a brief treatment with a lower concentration of caffeine (10 mM) potentiated the contracture. 45Ca2+ uptake studies showed that triphenyltin caused the muscle to accumulate Ca2+ which entered from external solution. Pretreatment with trypsin and dithiothreitol (a sulfhydryl-containing reducing agent) blocked the contracture induced by triphenyltin. These results suggest that triphenyltin initially interacts with the sulfhydryl groups of membrane bound proteins (possibly the Na+ channel) to cause depolarization of the muscle fibres. This depolarization triggers the release of Ca2+ from sarcoplasmic reticulum through the mechanism of Ca2+ inducing Ca2+ release, activates the contractile filaments and causes the muscle to contract. PMID- 7867696 TI - Meeting of the Section Calcium-Regulating Hormones and Bone Metabolism of the DGE. Hannover, October 30-November 1, 1994. Abstracts. PMID- 7867697 TI - Deiodination of thyroid hormones. A 30 year perspective (Berthold Memorial Award Lecture 1994). AB - It is truly a great honor to be the 1994 recipient of the Berthold Memorial Award from the German Endocrine Society which met in Wurzburg, March 2-5. I am especially indebted to Drs. Kohrle and Wuttke for their kindness in making our visit to Wurzburg so enjoyable and educational. Professor Berthold was the first to demonstrate the effects of a hormone on phenotypic expression when he transplanted testes to a castrated rooster, restoring its masculine appearance and behavior (Figure 1) (Berthold, 1849). Since 1960, when I joined the laboratory of the late Dr. Sidney H. Ingbar at the Thorndike Memorial Laboratory at the Boston City Hospital and Harvard Medical School, one of our major interest has been the peripheral metabolism of the thyroid hormones (Figure 2), especially the deiodination pathway (Figure 3). This review will be primarily based on our studies, although many other laboratories have made extremely important observations on thyroid hormone metabolism at the clinical, physiological, and molecular biological levels. I am indebted to many collaborators who have played major roles in many of the studies to be cited in this review. The principle colleagues are listed in Table 1. Since much of our work has been carried out simultaneously in rats, humans, and cell cultures, studies will be described under these three broad categories. PMID- 7867698 TI - Expression of insulin-like growth factor 1 (IGF-1) in the bovine oviduct during the oestrous cycle. AB - Growth factors are known to take part in the regulation of reproduction. Here we present evidence for the expression of insulin-like growth factor 1 (IGF-1) in the bovine oviduct. Two IGF-1 specific mRNA-transcripts of 1.5 and 4.4 kb were detected during the whole oestrous cycle, and showed increased expression after ovulation. Complete homology to the known IGF-1 sequence was achieved by specific RT-PCR (reverse transcription-polymerase chain reaction) amplification followed by dideoxysequencing of this 210 bp fragment. IGF-1 protein was localized in the secretory cells of the oviduct epithelium using immunohistochemical techniques. We suggest possible effects of IGF-1 during ovulation either on the oviductal cells or on the early embryo. PMID- 7867699 TI - Measurement of serum PDN-21 (Katacalcin) levels by radioimmunoassay in patients with various thyroid diseases. AB - We established a radioimmunoassay (RIA) using anti-PDN-21 antiserum, which was obtained by immunizing rabbits with synthesized PDN-21, and the basic results are described in this report, with discussion of the significance of PDN-21 determination in various thyroid diseases. In this RIA, the double antibody technique was used for B/F separation. This assay yielded excellent standard curves, specificity, recovery and reproducibility showing that the assay is satisfactory from the clinical standpoint. The upper limit of the normal PDN-21 level was 67 pg/ml in 98 healthy persons. Only patients with medullary carcinoma of the thyroid among patients with various thyroid diseases showed specifically positive assay results. The level was 110 to 18,300 pg/ml (mean, 5,940 pg/ml) in 7 patients whose levels were determined preoperatively, and 64 to 140,000 pg/ml (mean, 10,900 pg/ml) in 18 patients whose levels were determined postoperatively. Thus, PDN-21 levels increased very sharply in the settings of recurrence and tumor residue. These results suggest that PDN-21 has the potential to be an extremely sensitive, highly specific marker for medullary carcinoma of the thyroid. PMID- 7867700 TI - The effect of streptozotocin on the function of fetal porcine and rat pancreatic (pro-)islets. AB - Streptozotocin (STZ) is a broad spectrum antibiotic with anti-tumor and diabetogenic properties. Although STZ has been studied for many years, the exact mechanism of its diabetogenic action has not yet been fully elucidated. The present study investigated the effect of STZ on both fetal porcine proislets (FPP) and fetal rat islets (FRI) in an attempt to elucidate the diabetogenic effect of STZ on fetal pancreatic beta cells. This study demonstrates that after in vitro exposure of both FPP and FRI for 30 min to 2.2 mM and 4.4 mM STZ, respectively, FPP showed microscopically an intact structure, a spherical shape and a translucent color, while, in contrast, most FRI were disrupted and showed a slight white color with dark centers. Based on these data, we first transplanted FPP and FRI beneath the renal capsules of nude mice. Three to four weeks later, a single dosage of streptozotocin (180 mg/kg) was intravenously administered. Six of the seven nude mice pretransplanted with FPP became diabetic (blood glucose, BG, 308.08 +/- 33.62 mg/dl) within 2-5 days and then gradually achieved normoglycemia 51.56 +/- 7.71 days after STZ injection. After removal of the grafts, all of the six diabetic mice with normoglycemia returned to hyperglycemia (BG > 300 mg/dl). In contrast, all of the five nude mice pretransplanted with FRI persistently maintained hyperglycemia (BG > 300 mg/dl) and died 5 +/- 0.84 days after STZ injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867701 TI - Large-scale production of Ba(2+)-alginate-coated islets of Langerhans for immunoisolation. AB - Islet xenografts immunisolated in alginate capsules have been proposed by many groups for clinical islet transplantation. However, diffusion limitations and the total volume of microcapsules required for transplantation are, among other things, factors which have so far prevented successful clinical application. In this study, these problems have been overcome by immobilisation of rat and porcine islets in a Ba(2+)-cross-linked alignate matrix using an air jet droplet generator technique in combination with subsequent density-gradient purification. This procedure leads to high yields of islets coated with a tailored, thin layer of cross-linked alginate which protects the islets against cytotoxic compounds present in human plasma. The recovery of encapsulated rat and porcine islets was about 70%. Empty capsules were nearly completely removed. Using this technique, the total volume of the resulting microcapsules increased only by a factor of about 1.5 compared to the volume of free islets. The technique can be used for large-scale production of coated islets. PMID- 7867702 TI - Characterization of estrone hydroxylase activities in porcine endometrial cells. AB - The oxidation of estradiol to estrone in porcine endometrial cells is succeeded by hydroxylation at either 6 alpha- or 7 alpha-. The products are devoid of receptor affinity. Their formation is inhibited by cytochrome P450 blockers like ketoconazol but not by chloroquine and analogues. The hydroxylation at 6 alpha- proceeds with KM = 1.9 x 10(-7) M, that at 7 alpha- with KM = 3.6 x 10(-7) M. The respective values for the cytochrome P450-reductase cosubstrate NADPH are 1.7 x 10(-5) M and 1.9 x 10(-5) M. The kinetic parameters of the enzymes are compatible with a metabolic sequence: estradiol-->estrone--> 6 alpha/17 alpha-estrone. PMID- 7867703 TI - Thyroid volume and urinary iodine in school children and adolescents in Slovakia after 40 years of iodine prophylaxis. AB - The thyroid volume (by ultrasonographic volumetry) was estimated in 4,254 schoolchildren and adolescents 6-18 years of age from 12 districts of Slovakia and urinary iodine (by dry alkaline ashing followed by spectrophotometry) in 1,174 spot urine samples. No differences in thyroid volume or in iodine excretion between individual districts were found. Similarly, no differences in thyroid volume between sexes were found up to the age of 14 years, however, thereafter, such volumes were considerably higher in boys. When comparing our cummulated data with those reported by others for a population with optimal iodine intake, it was found: 1. the medians for most of the examined age groups were slightly higher, 2. the percentage of values which were higher than 97 percentiles of normal population was 3.01 for the age of 6-14 years, while that for the age of 15-18 years was 9.04. Only 35.9% of all values of urinary iodine were in the optimal range (i.e. 10-20 mud/dl), while 56.1 were less than 10 micrograms/dl and 15.9% less than 5 micrograms/dl, the remaining 8.0% over 20 micrograms/dl. In spite of long-term iodine prophylaxis (since 1949), the intake of iodine apparently is still not satisfactory, since a considerable amount of individuals appeared to be iodine deficient on the day of examination. Iodine intake, however, may be marginally sufficient up to the age of about 13-14 years, while later a higher number of enlarged thyroids was found which may be classified as goitre endemy grade I. PMID- 7867704 TI - Binding of 2-hydroxyestradiol and 4-hydroxyestradiol to the estrogen receptor of MCF-7 cells in cytosolic extracts and in nuclei of intact cells. AB - The catechol estrogens (CE), 2-hydroxyestradiol (2-OH-E2) and 4-hydroxyestradiol (4-OH-E2) were analyzed for their binding affinity to the estrogen receptor of MCF-7 cells. Applying a competitive binding assay to cytosols prepared from MCF-7 breast cancer cells, we measured a relative binding affinity of 23% (2-OH-E2) and 26% (4-OH-E2) compared to E2. Nuclear binding assays with the same cell line demonstrated a high specific binding with Kd's of 0.31 nM (2-OH-E2) and 0.21 nM (4-OH-E2). The relative binding affinity measured was 25% and 42% for 2-OH-E2 and 4-OH-E2, respectively. Based on this nuclear binding it can be concluded that the estrogen receptor occupied by CE is bound within the nucleus and might therefore be transcriptionally active. PMID- 7867705 TI - Blood pressure reaction during the intraoperative and early postoperative periods in patients with primary hyperparathyroidism. AB - Hypertension is a well known finding in primary hyperparathyroidism (HPT). In the present study, systolic blood pressure (SBP) and heart rate were recorded before, during and after surgery for HPT in 101 patients (mean serum calcium 2.96 +/- 0.22 mmol/l) and compared to 91 scheduled general surgical patients matched for age, sex, duration of surgery and type of general anesthesia. The HPT patients displayed an increased mean SBP, given as mean +/- standard deviation, both before (147 +/- 28 vs 131 +/- 25 mm Hg in controls) and during surgery (142 +/- 24 vs 117 +/- 21 mm Hg in controls) as well as postoperatively (141 +/- 23 vs 118 +/- 17 mm Hg in controls, all p < 0.0001). The preoperative SBP was correlated to both the intraoperative and postoperative SBP (r = 0.59 and r = 0.61, both p < 0.00001). However, the blood pressure elevation during and after surgery was still significant (both p < 0.001) when corrected for the influence of the preoperative blood pressure level using multiple regression analysis. The heart rate was increased in the HPT subjects only in the postoperative period (88 +/- 12 vs 83 +/- 12 beats/min in controls, p < 0.007). In conclusion, the systolic blood pressure was found to be elevated both before, during and after surgery in HPT subjects when compared to a general surgical population. In the postoperative period, also the heart rate was increased in the HPT subjects. These findings suggest an increased cardiovascular response to surgical stress in HPT subjects. PMID- 7867706 TI - Possible participation of prostaglandins in the increase in the bone blood flow in oophorectomized female rats. AB - The aim of this study was to verify the possible role of prostaglandin (PG) in the increase in the bone blood flow of female rats after oophorectomy (OOX). In two experiments we determined blood flow in the tibia and distal femur (85Sr microspheres) and 24-h incorporation of 45Ca and 3H-proline. Acetylosalicyclic acid (ASA, 0.13% in the food for 4 weeks) was used to suppress the production of PG. There was an increase in the bone blood flow after OOX (performed 4 weeks prior to the experiment), no change after ASA alone and significant reduction by ASA of the OOX-induced increase in the bone blood flow. In both groups of OOX females there was a decrease in tibial bone density and ash weight. The changes in 45Ca incorporation were similar to those in the blood flow while the changes in 3H-proline incorporation were not significant. Thus, the effect of ASA, i.e. suppression of the OOX-induced increase in the bone blood flow, is consistent with the possible role of PG (probably PGE2) in the increase in bone blood flow of OOX female rats. PMID- 7867707 TI - Effects of hydrogen peroxide and phorbol myristate acetate on endothelial transport and F-actin distribution. AB - We have previously reported that both hydrogen peroxide (H2O2) and phorbol myristate acetate (PMA) can stimulate endocytosis in bovine aortic endothelial cells. Moreover, we have found that redistribution of filamentous actin (F-actin) in a low concentration of cytochalasin B also increases such endocytic activity. In the present study, the effects of H2O2 and PMA on endothelial transport and F actin distribution were studied in bovine aortic endothelial monolayers. A low concentration of H2O2 (10(-5) M) had no effect on permeability, but did cause redistribution of F-actin, i.e., the diffuse arrangement of filaments changed to a clear stress-fiber pattern, but the dense peripheral filament bands were not affected. A 10-fold higher concentration of H2O2 (10(-4) M), which increases permeability as we reported previously, caused a disruption of F-actin dense peripheral bands. PMA had a concentration-dependent effect on endothelial permeability and F-actin distribution, i.e., 10(-7) M PMA had no observed effect on permeability and no effect on F-actin structure either, whereas 5 x 10(-7) M PMA caused decreased permeability during the first 1 to 1.5 h and thereafter increased permeability for up to 6 h. There was also a time-dependent reorganization of F-actin structure after the treatment with 5 x 10(-7) PMA: the number of dense peripheral bands increased after 1 h of exposure; these bands had a ruffled appearance after 2 h and were disrupted after 6 h. These results suggest that, in endothelial cells, F-actin plays a role in regulating the width of intercellular junctions and thereby controls the paracellular pathway of vascular permeability. PMID- 7867709 TI - Mechanical properties of the extracellular matrix influence fibronectin fibril assembly in vitro. AB - Mechanical properties of the extracellular matrix (ECM) are proposed to influence cell behavior and biological activity. The influence of the mechanical environment on fibronectin fibril assembly was evaluated. Fibroblasts were cultured in hydrated collagen gels with two distinctly different mechanical properties. Cells cultured within a stabilized collagen gel generate stress that is transmitted throughout the matrix (stressed gel). In contrast, cells that are cultured within a collagen gel that is floating freely in media do not generate stress (relaxed gel). Fibroblasts in the stressed collagen gel develop large bundles of actin microfilaments and associated fibronectin fibrils, while fibroblasts within relaxed gels do not form stress fibers or assemble fibronectin into fibrils. In addition, we have evaluated the mechanism of fibronectin fibril assembly employed by fibroblasts cultured within a stressed three-dimensional collagen matrix and the role of fibronectin fibrils in transmission of cell generated forces to the surrounding matrix. Fibronectin fragments (70-kDa amino terminal fragment, 110-kDa cell-adhesive fragment, and GRGDS peptide) and a monoclonal antibody body blocked fibronectin fibril assembly in stressed three dimensional collagen gels. These results suggest that the features of fibronectin required for fibronectin fibril assembly by cells in collagen gels is similar to those required by cells cultured on a planar substratum. Although fibronectin fibril assembly was blocked by these inhibiting fragments and antibody, the cells displayed prominent actin bundles and developed isometric tension, indicating that stress fiber formation and contractile force transmission is not dependent on the presence of fibronectin fibrils. PMID- 7867708 TI - Xeroderma pigmentosum variant: generation and characterization of fibroblastic cell lines transformed with SV40 large T antigen. AB - Xeroderma pigmentosum variant (XPV) fibroblasts from the XP4BE strain (CRL1162) were transformed with the SV40 large T antigen with the purpose of generating immortalized cell lines that are defective in post-replication repair (PRR). Two transformation and selection protocols were used and at least two independent clones were obtained, which behaved in culture as immortal cell lines. Fingerprinting analyses were used to demonstrate their origin from XP4BE cells and to compare their genetic profiles. These cell lines were shown to be hypersensitive to killing by uv when compared to SV40-transformed fibroblasts derived from foreskins of normal neonates. One of the XPV transformed cell lines (CTag) was characterized further as a potential source of cell-free extracts with capability for catalyzing the T antigen-dependent in vitro replication of plasmid DNA carrying the SV40 origin of replication. In this assay system, CTag extracts were shown to be as active as those produced from HeLa cells. In vitro replication of uv-damaged plasmid DNA by protein extracts from PRR-defective (XPV) and PRR-proficient cells might allow the identification and characterization of protein factors that contribute to normal replication of uv damaged DNA. Ultraviolet irradiation of plasmid DNA templates caused dose dependent inhibition of in vitro replication by both HeLa and CTag extracts. PMID- 7867710 TI - Ganglioside GT1b induces keratinocyte differentiation without activating protein kinase C. AB - The altered patterns of expression of gangliosides during density-dependent growth inhibition, oncogenic transformation, and embryogenesis suggest that gangliosides, sialylated membrane glycolipids, may affect cellular proliferation and differentiation. Gangliosides of the "b" pathway of ganglioside synthesis, including GM3, GD3, and GD1b, inhibit the proliferation of cultured keratinocytes without increasing differentiation. We have examined the effect on keratinocyte proliferation and differentiation of supplemental ganglioside GT1b, a more highly sialylated ganglioside of the "b" synthetic pathway that is also present in cultured keratinocytes. In contrast to the lack of effect on differentiation of these other gangliosides, we noted significant induction of keratinocyte differentiation by GT1b, as evidenced by early desmosome formation, and increased cornified envelope formation and expression of involucrin and of the differentiation-specific keratin K1. The addition of GT1b did not cause a shift in intracellular free calcium or alter protein kinase C activity. Alterations in the membrane concentration of ganglioside GT1b, a minor ganglioside component of the keratinocyte membrane, may participate in regulating keratinocyte differentiation. PMID- 7867711 TI - Cell cycle-specific and transcription-related phosphorylation of mammalian topoisomerase I. AB - Eukaryotic DNA topoisomerase I has been recently shown to be associated with the transcriptional machinery and has also been implicated to function in DNA replication and perhaps other DNA transactions. We have identified several differentially phosphorylated forms of mammalian topoisomerase I as electrophoretic variants by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These differently phosphorylated forms cleave chromosomal DNA in cells and also relax supercoiled DNA with about equal activity, suggesting that they primarily function other than to activate catalysis. One of the phosphorylated forms is specifically present during mitosis. Upon transition from mitosis into G1 phase, two forms differing in phosphorylation state appear and persist throughout the remainder of interphase. When cells are incubated in a pellet, one of the interphase phosphorylated forms disappears coincidentally with an increase in the abundance of the other; if the cell pellet is disrupted and the cells are reincubated in suspension, the forms rapidly shift back to their original abundance levels. Finally, a shift in relative abundance of the differently phosphorylated interphase forms is observed when transcription is inhibited. These results suggest that dynamic phosphorylation and dephosphorylation regulate topoisomerase I during RNA transcription and cell cycle progression. PMID- 7867712 TI - Intracellular processing of talin occurs within focal adhesions. AB - CHO cells spread out on fibronectin-coated plastic were perforated with the bacterial toxin alveolysin. This treatment preserves the integrity of the cells but opens large and stable hydrophilic pores on the plasma membrane. With these semi-intact cells, it has been possible to have a direct access to adhesion plaques. Furthermore, with this procedure one can determine the distribution of a single intracellular protein between membrane-associated and cytosolic pools. The introduction within the perforated cells of polyclonal antibodies raised against talin induced the detachment of the cells. This provides direct evidence that talin is required to stabilize the adhesion plaques. Furthermore, immunoprecipitation of talin in the membrane-associated and cytosolic fractions indicated that the membrane-associated talin was cleaved and reduced to a stable 200-kDa fragment. Conversely, soluble talin remained intact. This 200-kDa fragment was similar to the proteolytic fragment produced from talin by calpain II. Analysis of whole cell extracts and pulse chase experiments indicated that this proteolysis also occurred in vivo, although to a smaller extent. The kinetics of the limited proteolytic cleavage of talin suggested that the 200-kDa fragment was first produced within focal adhesion, and secondarily released into the cytosol. PMID- 7867713 TI - Heat shock-induced accumulation of 70-kDa stress protein (HSP70) can protect ATP depleted tumor cells from necrosis. AB - The phenomenon of cell resistance to prolonged energy deprivation after mild thermal stress was studied in vitro. Murine P3O1 myeloma and Ehrlich ascites carcinoma cells were treated with rotenone (an inhibitor of respiration) in glucose-free medium to block ATP generation. ATP rapidly decreased in these cells to 3-6% of the initial level that resulted in powerful aggregation of cytoskeletal proteins, blebbing, and necrotic death of 60-70% cells within 2 h. Prior heat shock (43 degrees C for 10 min) with a subsequent 3-h recovery in a rich medium considerably suppressed the rotenone-induced actin aggregation and rate of necrosis in the energy-deprived cells without effecting the ATP drop in them. Using [14C]leucine labeling, gel electrophoresis, and fluorography, stimulation of the heat-shock protein (HSP) synthesis and total suppression of any other translation were revealed in the cells during recovery after the heat pretreatment. Significantly elevated levels of HSP70 but not HSP90 and HSP27 were found by means of immunoblotting in both cell cultures rendered resistant to necrosis under ATP-depleting conditions. Inhibition of the thermo-induced HSP synthesis by cycloheximide fully prevented development of the tolerance to energy deprivation. A novel function of HSP70 consisting of protection of ATP-deprived cells from "lethal" aggregation of cytoskeletal proteins is suggested. PMID- 7867714 TI - Phorbol myristate acetate selectively stimulates apical endocytosis via protein kinase C in polarized MDCK cells. AB - We have examined the regulation of endocytosis in polarized Madin-Darby canine kidney (MDCK) cells. Using quantitative electron microscopy and biochemical measurements, we found that incubation with the tumor promoter phorbol 12 myristate 13-acetate (TPA) stimulated endocytosis of horseradish peroxidase (HRP) and ricin four- to fivefold at the apical side in MDCK cells, whereas the uptake at the basolateral membrane was unaffected. The use of several protein kinase inhibitors and TPA analogues indicated that the stimulation of apical endocytosis was mediated via protein kinase C independently of protein kinase A. This stimulation occurred even when the clathrin-dependent pathway was inhibited by acidification of the cytosol, suggesting that the TPA-stimulated uptake was associated with a clathrin-independent mechanism. Moreover, we found that TPA also stimulated recycling of ricin to the apical domain. Ultrastructural analysis of MDCK cells preincubated with TPA revealed that neither the morphology nor the size of the endosomes was altered compared to control cells. Using morphometry, no marked change in the apical plasma membrane area was detected after incubation with TPA. These data indicate that the TPA-stimulated endocytosis involved neither ruffling nor formation of macropinosomes in MDCK cells. Finally, we found that TPA also selectively stimulated apical endocytosis in the human colon adenocarcinoma cell line (Caco-2). The data suggest that protein kinase C is involved in a strong stimulation of apical endocytosis and might participate in the regulation of membrane trafficking between the apical plasma membrane and apical endosomes in polarized epithelial cells. PMID- 7867715 TI - Role of the heparin-binding domain of chimeric peptides derived from fibronectin in cell spreading and motility. AB - Cellular responses to fibronectin (FN) are likely to have a complex molecular basis involving the interactions between multiple functional domains of FN and specific cell surface molecules. We have utilized several types of recombinant FN fragments and their chimeric fragments to examine the regulatory mechanisms of the spreading and chemotactic migration of HT1080 human fibrosarcoma cells on FN. The CH-271 fusion fragment, in which the cell-binding domain (C-274) of FN is adjacent to the heparin-binding domain (H-271), promoted cell spreading more efficiently than C-274, H-271, or their mixture (C-274 + H-271) over a 60-min incubation. The CH-271 variants containing various modules in the heparin-binding domain (CHV peptide) showed different promotion of cell migration, spreading, and vinculin accumulation at focal adhesion, respectively. The preincubation of the cells with heparitinase I resulted in significant inhibition of chemotactic migration to FN and its fragments containing the III13 and/or III14 modules of the heparin-binding domain. Additionally, migration to CH-271 was inhibited by the presence of the RGDS peptide in a concentration-dependent fashion. Thus, the spread and migration responses of HT1080 cells onto FN fusion peptides require the adjacent coexistence of cell- and heparin-binding domains and are mediated by the interactions between cell surface heparan sulfate and the heparin-binding domain, in concert with the interaction between cell surface integrin and the cell-binding domain. In conclusion, our present study demonstrated that fusion peptides of fibronectin can efficiently induce two signals from the cell-binding and heparin-binding domains required for the completion of cell spreading, the formation of focal contact, and motility at the early stage of the culture, suggesting that the III13 or III14 modules within the heparin-binding domain are responsible for the initiation of different cellular responses. PMID- 7867716 TI - Migrating vascular smooth muscle cells polarize cell surface urokinase receptors after injury in vitro. AB - The localization of proteases to cell surfaces via receptors may facilitate cell migration, invasion, and matrix degradation. Since vascular smooth muscle cell (SMC) migration may be an important event in atherosclerosis and in intimal thickening after vascular injury, we studied the cell surface expression of a receptor for urokinase-type plasminogen activator (u-PAR) in cultured human vascular SMC. Using immunofluorescence microscopy, we demonstrated several staining patterns of SMC u-PAR: at the periphery of the cell membrane, at the leading edge, and at cell-cell contact sites. When migration experiments were performed using a wound assay, one-third of the SMC at the wound edge demonstrated polarization of cell surface u-PAR toward the leading edge of the cell membrane (32 +/- 2%, +/- SEM, n = 7). A similar pattern was seen with an antibody to caveolin, a transmembrane protein found in caveolae, but not with an antibody to 5'-nucleotidase, another cell surface glycophosphatidylinositol anchored protein, which was homogeneously expressed on the cell surface. Low density lipoprotein receptor-related protein, which mediates internalization of u PAR bound ligands, was distributed in a diffuse punctate pattern, not polarized to the leading edge. Double immunofluorescent studies demonstrated codistribution of SMC u-PAR with vinculin and caveolin in migrating SMC at the leading edge in a wound assay. Polarization of cell surface u-PAR was not observed in either nonwounded or subconfluent cultures, despite random migratory behavior. These studies suggest that in response to wounding, human vascular SMC polarize and concentrate cell surface u-PAR to their leading edge, perhaps facilitating directional migration. PMID- 7867717 TI - Specialization switch in differentiating embryonic rat liver progenitor cells in response to sodium butyrate. AB - Embryonic (E) 12 rat liver epithelial cells constitute a population of bipotential progenitor cells which can differentiate along the hepatocyte (Hep) or biliary epithelial cell (BEC) lineage in primary culture. In the present study, E12 cells were seeded on fibronectin-coated substratum and exposed to sodium butyrate (SB) for various exposure times, and the emergence of the Hep or BEC phenotype was monitored by following the variations in albumin production and assessing the appearance of the two surface-exposed markers HES6 and BDS7. Continuous exposure to SB resulted into a major reduction in albumin production and, at Day 9 postseeding, few cells coexpressed BDS7 and albumin. When cells were exposed to SB for 5 days and then cultured for an additional 5 days without SB, they massively express BDS7, but very little HES6. Moreover, the reverse sequence, i.e., 5 days without SB followed by 5 days with it, led to the appearance of many cells expressing both HES6 and BDS7. These results indicate that progenitors committed preferentially along the Hep lineage still have the option to switch to BECs, at a transitional stage that we refer to as a "differentiation window." PMID- 7867718 TI - Nucleocytoplasmic transport of the Rev protein of human immunodeficiency virus type 1 is dependent on the activation domain of the protein. AB - The human immunodeficiency virus type 1 (HIV-1) regulatory protein Rev, which is required for the cytoplasmic expression of unspliced and incompletely spliced viral mRNAs, is located predominantly in the nucleolus. In this study, we show that Rev translocates from the nucleolus to the cytoplasm in HeLa and COS cells transfected with Rev under conditions where rRNA synthesis is inhibited (e.g., with actinomycin D). Dominant-negative mutants with mutations in the activation domain of Rev, which are known to inhibit wild-type Rev function in trans, are unable to leave the nucleus upon actinomycin D treatment. More importantly, when present in excess, these mutants inhibit the translocation of wild-type Rev. This correlation of inhibitory activities suggests that Rev function depends on its transport to and presence (at least transient) in the cytoplasm. In this context, we discuss the possibility that Rev is actively involved in the transport of HIV 1-specific mRNAs containing the Rev response element (a highly structured RNA sequence, which is specifically recognized by the Rev trans-activator). We also discuss the potential of nucleocytoplasmic export of Rev as a target for anti-HIV chemotherapy. PMID- 7867719 TI - Carbon and energetic uncoupling are associated with block of division at different stages of the cell cycle in several cdc mutants of Saccharomyces cerevisiae. AB - Cell proliferation arrest at 37 degrees C (restrictive temperature) of the cell division cycle (cdc) mutants of Saccharomyces cerevisiae cdc28, cdc35, cdc19, cdc21, and cdc17 was correlated with carbon and energy uncoupling. At 37 degrees C, cdc mutants diverted to biomass synthesis only 3 to 4% and 8 to 24% of the fluxes of carbon consumed and ATP obtained by catabolism, respectively, compared with 48 and 34% in the wild-type strain A364A. At the permissive temperature (25 degrees C), the wild type showed similar carbon and energy coupling indexes as at 37 degrees C. However, carbon and energy coupling indexes were two- to sevenfold higher at 25 degrees than at 37 degrees C in cdc mutants; e.g., at 25 degrees C two- to sevenfold higher amounts of carbon and ATP were directed to biomass production than at 37 degrees C. The wild-type strain exhibited a purely oxidative glucose catabolism at 37 degrees C (RQ approximately 1.0), while the cell proliferation arrest of cdc mutants at the same temperature was characterized by fermentative metabolism. At 37 degrees C, cdc mutants directed 50 to 60% of the carbon to ethanol production; 3 to 12% of the carbon was recovered as glycerol in cdc mutants as well as in the wild type. The proliferation arrest of the cell division cycle mutant cdc28 correlated with a significant decrease in the incorporation of radioactive precursors into DNA, RNA, and proteins. In the presence of 8-hydroxyquinoline, the wild-type strain underwent cell proliferation arrest and also exhibited metabolic uncoupling with bioenergetic and catabolic behavior similar to that of the cdc mutants at 37 degrees C. Experimental evidence obtained with cdc19, whose defective gene product is pyruvate kinase, suggests that the primary defect of cdc mutants correlates with a metabolically, highly uncoupled yeast cell. The results presented point to the existence of strong carbon and energy uncoupling together with cell division arrest exhibited by cdc mutants at the restrictive temperature. The degree of uncoupling appears to be tuned, at least in part, by the increase in flux of sugar catabolism through the ethanol fermentative pathway. PMID- 7867720 TI - Carbon and energy uncoupling associated with cell cycle arrest of cdc mutants of Saccharomyces cerevisiae may be linked to glucose-induced catabolite repression. AB - Several cell division cycle (cdc) mutants of Saccharomyces cerevisiae (cdc28, cdc35, cdc19, cdc21, and cdc17) at the restrictive temperature (37 degrees C) in the presence of 1% glucose and defined medium divert most of the carbon (approximately 50%) to ethanol production with low biomass growth yields (Yglc) that correlate with carbon and energy uncoupling and arrest of cell proliferation. The cdc mutants studied are shown to be glucose-repressed, while this was not the case for the wild-type A364A (WT). At 37 degrees C, in the presence of 1% glycerol, derepressed cdc28 mutant cells did not show arrest of cell division and carbon and energy uncoupling since the Yglc levels measured were similar to those of the WT strain. These results suggest that the increased fermentative ability and carbon and energy uncoupling exhibited in the presence of glucose by cdc mutants with respect to those exhibited by the WT may be due to catabolite repression. PMID- 7867721 TI - The mechanism of binding of exogenous DNA to sperm cells: factors controlling the DNA uptake. AB - Mature sperm cells have the spontaneous capability of taking up exogenous DNA. Potential substrates for the interaction of the DNA with the sperm heads are specific classes of DNA-binding proteins. In the present work three major classes of DNA-binding proteins were identified by Southwestern analysis of sperm head protein extracts: a first class of about 50 kDa in molecular weight, a second one of 30-35 kDa, and finally a third one below 20 kDa. The latter group most probably contains sperm protamines. Our attention was particularly focused on the 30- to 35-kDa proteins as a substrate for DNA binding, as they represented the only group whose electrophoretic mobility was conserved among mammalian species. In addition they were the only class of DNA-binding proteins accessible to exogenous DNA in intact sperm cells. The purified 30- to 35-kDa proteins interacted in vitro with exogenous DNA and generated discrete protein/DNA complexes as determined by band shift assay. A factor blocking the binding of exogenous DNA to sperm cells was also identified in the seminal fluid of mammals and in echinoid spermatoza. The factor also exerted a powerful inhibitory effect on DNA uptake in sperm cells of heterologous species. The 30- to 35-kDa DNA binding proteins appeared to be the specific target through which the inhibition was mediated. In the presence of the inhibitory factor, the 30- to 35-kDa lost the ability to bind exogenous DNA. Thus, the interaction of exogenous DNA with sperm cells does not appear to be a casual event but, on the contrary, relies on a molecular mechanism based on the cooperation of specific protein factors. PMID- 7867722 TI - Plasminogen activator inhibitor type 2: an intracellular keratinocyte differentiation product that is incorporated into the cornified envelope. AB - Human epidermal keratinocytes synthesize a complex plasminogen activator proteolytic cascade, consisting of two plasminogen activating enzymes and two inhibitors, that is thought to play a role in epidermal migration and differentiation as well as in several cutaneous diseases. Quantification of the plasminogen activator cascade proteins in keratinocytes reveals that plasminogen activator inhibitor type 2 (PAI-2) is distinct from the other components (i.e., urokinase and tissue-type plasminogen activators and inhibitor type 1) in several respects: (i) PAI-2 remains mostly cell-associated, rather than secreted; (ii) The level of cell-associated PAI-2 is at least 50-fold greater than that of the other components; (iii) PAI-2 is the only component whose level is enhanced upon elevation of the Ca2+ concentration, which is well known to induce a more differentiated phenotype in keratinocyte culture. Immunocytochemical localization experiments reveal that most keratinocytes contain PAI-2, which in a subpopulation of more differentiated cells is resistant to detergent extraction. Additional immunocytochemical localization and immunoblot experiments demonstrate that some of the PAI-2 becomes incorporated into the cornified envelope during terminal differentiation of the keratinocyte. These studies raise the possibility that PAI-2 may have an intracellular role associated with the terminal stage of keratinocyte differentiation. PMID- 7867723 TI - Regulation of differentiated phenotype of rat hepatic lipocytes by retinoids in primary culture. AB - Activation of hepatic lipocytes to myofibroblastlike cells observed in cell culture and during liver fibrogenesis is characterized by an increase in collagen formation and cell proliferation. These changes appear to be associated with the loss of intracellular retinoid in lipocytes, the principal storage site for vitamin A in the body. To evaluate whether retinoids have the capability to suppress lipocyte activation, we exposed cultured lipocytes in both native and myofibroblastlike states to retinoids and determined their effects on collagen production, intracellular retinoid level, and cell proliferation. Retinol (1 microM) and retinoic acid (1 microM) supplementation of primary rat lipocyte cultures inhibited the spontaneous increase in collagen synthesis associated with lipocyte activation; lower concentrations of retinol (10 or 100 nM) were also effective. Simultaneously, retinol addition prevented a precipitous decline in intracellular retinoid content in the absence of added retinoid. These retinoid effects were reversed by a change to unsupplemented control medium. When cells in the myofibroblastlike state were exposed to retinol (> or = 1 microM), a significant increase in intracellular retinoid levels and reduction in collagen synthesis occurred. Lipocytes in both native and myofibroblastlike states secreted four to five times higher amounts of type I collagen than type III collagen, but retinol and retinoic acid particularly inhibited production of type I collagen. Cell proliferation measured by [3H]thymidine incorporation was also inhibited by retinol. These results demonstrate that extracellular retinoids suppress lipocyte-activated collagen synthesis and cell proliferation and support the interpretation that retinoids themselves are regulatory factors in maintenance of the lipocyte in its native, differentiated state. PMID- 7867724 TI - ets-2 regulates cdc2 kinase activity in mammalian cells: coordinated expression of cdc2 and cyclin A. AB - ets-2 is a member of a family of transcription factors implicated in the regulation of gene expression during cell proliferation, cell differentiation, and development. We report that the ets-2 protein transactivates the promoter of the cdc2 gene which encodes a 34-kDa serine-threonine kinase required for mitotic initiation in mammalian cells. Transactivation occurs via specific interaction with multiple ets binding sites in the 5' flanking region of the gene. In BALB/c3T3 rodent fibroblasts constitutively expressing ets-2 and cultured in either 10 or 0.5% serum, cdc2 expression and its associated histone H1 kinase activity are increased, compared to control cells. Such increased activity correlates with elevated levels of cyclin A but not cyclin B1. Furthermore, ets-2 transfected, but not parental, BALB/c3T3 cells, grow under low serum conditions, albeit at a reduced rate. These data demonstrate that ets-2 plays a direct role in the regulation of cdc2 expression and raise the possibility that ets-2 participates in the coordinated regulation of cdc2 cyclin A expression which is essential for the modulation of cdc2-regulated processes. PMID- 7867725 TI - Mimosine differentially inhibits DNA replication and cell cycle progression in somatic cells compared to embryonic cells of Xenopus laevis. AB - The plant amino acid mimosine has been reported to block cell cycle progression and DNA replication in cultured mammalian cells, perhaps by blocking initiation. In this study, we show that mimosine does not block initiation or any other step in DNA replication in embryonic cells of Xenopus laevis. Mimosine does not block DNA replication in cell-free "cycling" extracts of Xenopus eggs, nor does it block M to S phase transition in cell-free egg extracts released from metaphase arrest. Microinjection of mimosine into 4-cell embryos had no visible effect on development during the first 3 days after fertilization. Prior to the midblastula transition, when the cell cycle consists of alternating S and M phases, neither chromosomal DNA replication nor replication of microinjected plasmid DNA were inhibited by mimosine microinjected into cleaving Xenopus embryos. Microinjection of mimosine after the midblastula transition, when large endogenous stockpiles of DNA replication components have begun to be depleted and Xenopus embryonic cells have acquired G1 and G2 phases, still did not inhibit cell cycle progression or DNA replication. In marked contrast, mimosine arrested the growth of proliferating cultured Xenopus kidney epithelial A6 cells near the G1/S boundary. We conclude that mimosine appears to block DNA replication and cell cycle progression in somatic cells, but has no apparent effect in rapidly dividing Xenopus embryonic cells. PMID- 7867726 TI - Induction of RET proto-oncogene expression in neuroblastoma cells precedes neuronal differentiation and is not mediated by protein synthesis. AB - RET proto-oncogene products are involved in neural crest development, and constitutional RET mutations are associated with syndromes characterized by tumors of neural crest origin. To study the regulation of RET transcription during neuronal differentiation we analyzed RET expression in neuroblastoma cell lines treated with various differentiating agents. A marked increase in RET mRNA levels was observed in all the cell lines examined shortly after retinoic acid (RA) treatment and before the onset of detectable morphological changes. Upregulation of RET expression was also found in SK-N-BE cells induced to differentiate by 12-O-tetradecanoylphorbol-13-acetate, glial cell-conditioned medium, alpha or gamma interferon, and in SH-SY-5Y cells exposed to nerve growth factor. Induction of RET expression by RA occurred in the absence of de novo protein synthesis. On the other hand, cycloheximide treatment by itself caused upregulation of RET transcripts. These results indicate that the positive transcriptional regulation of RET is closely associated with early neuronal differentiation and suggest that a negative regulatory factor/s controls RET transcription in neuroblastoma cells. Finally, anti-Ret antibodies immunoprecipitated four bands with apparent molecular weights of 150, 155, 170, and 175 kDa in RA-induced SK-N-BE cells. These bands likely represent differently glycosylated forms of the two RET primary products (117 and 122 kDa) detected in tunicamycin-treated cells. PMID- 7867727 TI - A review of the possible mechanisms for the persistence of foot-and-mouth disease virus. PMID- 7867728 TI - Urinary isolates of apramycin-resistant Escherichia coli and Klebsiella pneumoniae from Dublin. AB - Twenty-two gentamicin-resistant urinary isolates of Escherichia coli and five gentamicin-resistant urinary isolates of Klebsiella pneumoniae from a Dublin hospital were examined for resistance to the veterinary aminoglycoside antibiotic apramycin. Five isolates of E. coli and one isolate of K. pneumoniae were found to be resistant. The apramycin-resistant isolates, which were also resistant to the veterinary anthelmintic agent hygromycin B, hybridized with a DNA probe for the gene encoding the enzyme 3-N-aminoglycoside acetyltransferase type IV (AAC(3)IV). Resistance to apramycin and hygromycin B was co-transferable in four of the five isolates of E. coli and the isolate of K. pneumoniae. In one isolate of E. coli apramycin resistance was not transferable. On the basis of their restriction enzyme digestion profiles and the antimicrobial resistance traits encoded, the transferable plasmids encoding resistance to apramycin and hygromycin B comprised three distinct types. Genetic linkage between the gene encoding AAC(3)IV and genes encoding resistance to ampicillin and either tetracycline or trimethoprim, means that the relatively widespread use of these antimicrobial agents provides a selective pressure for the persistence of resistance to apramycin and gentamicin even in the absence of bacterial exposure to aminoglycosides. PMID- 7867729 TI - Clonal diffusion of EPEC-like Escherichia coli from rabbits as detected by ribotyping and random amplified polymorphic DNA assays. AB - The genetic diversity and clonal relationships among 77 Escherichia coli strains isolated in France from diarrhoeic rabbits and that belonged to seven O serogroups including the predominant O103 serogroup, were estimated by ribotyping and random amplified polymorphic DNA (RAPD) assays. Fifteen ribotypes were defined. Most of the highly pathogenic O103 strains could be assigned to two major groups. Non-pathogenic strains were clearly distinguished. RAPD assays generally matched ribotyping, or gave more precision for subdividing strains from the two main O103 groups. The results on strains isolated from different areas and over a 9-year period showed the relevance of the association of these two methods for the survey of the spread of strains in breeding flocks and illustrated clonal diffusion in rabbit production structures. PMID- 7867730 TI - Molecular typing of Acinetobacter baumannii-Acinetobacter calcoaceticus complex isolates from endemic and epidemic nosocomial infections. AB - Ribotype, biotype and resistance phenotype were used to characterize 37 Acinetobacter baumannii-A. calcoaceticus complex isolates responsible for nosocomial infections in Buenos Aires. Nineteen isolates were recovered from endemic infections at 2 hospitals and 18 represent an intensive care unit outbreak that occurred in a third hospital. By ribotyping isolates were classified into five different clones of A. baumannii biotype 2, 3 of A. baumannii biotype 9, and 3 of Acinetobacter genospecies 13. Combination of the three epidemiological markers permitted categorization of 18 outbreak isolates into four probable strains: 2 A. baumannii biotype 2, named type I, and II, and 2 A. baumannii biotype 9. Type I (15 isolates) was the most prevalent strain at one hospital and was responsible for the outbreak. In conclusion, combined analysis of biotypes, resistance phenotypes, and ribotypes was an accurate approach for epidemiologic investigation of A. baumannii. Furthermore, ribotyping discriminated Acinetobacter genospecies 13 isolates which were phenotypically difficult to type. PMID- 7867731 TI - Host-microflora interaction in systemic lupus erythematosus (SLE): circulating antibodies to the indigenous bacteria of the intestinal tract. AB - Experimental data suggest a role for the microflora in the disease expression of systemic lupus erythematosus (SLE). In active SLE anti-ds-DNA antibodies are supposed to be pathogenic by forming immune complexes with DNA. Bacteria might induce the production of anti-ds-DNA antibodies. To explore the relation between the host and his microflora in SLE in comparison with healthy controls we studied the prevalence of systemic antibodies to faecal bacteria that were discriminated by their morphology by indirect immunofluorescence. IgM titres against their own faecal microflora were found to be lower both in active and inactive SLE when compared to healthy individuals. IgG-class antibacterial antibodies were increased in inactive SLE but decreased in active SLE compared to inactive SLE and healthy controls, although plasma levels of total IgG were almost doubled in active SLE. The lower IgG antibacterial antibody titres in active SLE might possibly result from sequestration of these IgG antibodies in immune complexes, indicating a possible role for antibacterial antibodies in exacerbations of SLE. PMID- 7867732 TI - A comparative study of food retail premises by means of visual inspection and microbiological quality of food. AB - The relationship between visual inspection ratings given to ten food retail premises and the microbiological quality of food samples was examined. Viable counts of bacteria and of Staphylococcus aureus were determined for cooked meat samples from each of the premises. There was no correlation between potential risk of foodborne infection, as assessed by total inspection rating, and bacteriological counts in food (P < 0.05). Neither was there a consistent relationship between scores given to any component of the total rating and the bacteriological quality of food. The effectiveness of the current UK inspection scheme in assessing risk of foodborne infection is questioned. Inclusion of appropriately weighted criteria such as food temperature abuse is suggested to improve the scheme. PMID- 7867733 TI - Direct milk excretion of Campylobacter jejuni in a dairy cow causing cases of human enteritis. AB - Consumption of milk contaminated with Campylobacter jejuni has been described as a cause of human enteritis. Although faecal contamination of milk with the organism has frequently been described, direct milk excretion of Campylobacter jejuni into milk has rarely been linked with cases of human infection. We describe the investigations undertaken following the isolation of Campylobacter jejuni from samples of unpasteurized milk prior to retail. Results of epidemiological investigations including typing of Campylobacter jejuni isolates using pyrolysis mass spectrometry, Penner and Lior serotyping, biotyping, phage typing and restriction fragment length polymorphism analysis provided convincing evidence implicating direct milk excretion of Campylobacter jejuni by one asymptomatic dairy cow as the source of the milk contamination and the cause of local cases of human enteritis. PMID- 7867734 TI - Population genetics of Mycobacterium tuberculosis complex in Scotland analysed by pulsed-field gel electrophoresis. AB - The results of typing of 121 strains in the Mycobacterium tuberculosis complex by PFGE are presented. Every isolate from patients in Scotland over a 3-month period for M. tuberculosis and for 1 year for M. bovis were included along with several laboratory strains including those of BCG. The PFGE results suggest that the population structure of all the strains in this complex is distinctly simple with limited genetic diversity and also suggest that M. bovis is not a distinct species. PMID- 7867735 TI - DNA typing of epidemiologically-related isolates of Aspergillus fumigatus. AB - Invasive aspergillosis is often nosocomially acquired and carries a high mortality. Molecular typing methods to discriminate isolates have now been developed. Using simple restriction endonuclease (Sal1 and Xho1) digestion of total genomic DNA, we have typed 25 epidemiologically-related isolates of A. fumigatus from six hospital episodes of invasive aspergillosis. Eight DNA types were found and in each case the DNA type matched precisely the epidemiological data. Thus DNA typing of A. fumigatus can provide the means to match isolates from linked sources and distinguish isolates from diverse origins. PMID- 7867736 TI - Genotypic evaluation of rickettsial isolates recovered from various species of ticks in Portugal. AB - Twelve rickettsial isolates, from Rhipicephalus sanguineus, R. turanicus, Dermacentor marginatus and Hyalomma marginatus, were subjected to genotypic analysis. Amplification of specific DNA sequences, restriction endonuclease digestion of amplified DNA products, and gel electrophoresis were used to identify specific DNA fragment-banding patterns. Five patterns were resolved. Four were homologous with those of previously described rickettsial genotypes, R. conorii, R. slovaca, R. rhipicephali and R. massiliae. The fifth pattern differed by only a single altered restriction endonuclease cleavage site. For the first time in Portugal a widely distributed spectrum of spotted fever group rickettsia was found among potential vector species stressing the need to determine their potential for human and domestic animals infection. PMID- 7867737 TI - The occurrence of Mycobacterium bovis infection in cattle in and around an area subject to extensive badger (Meles meles) control. AB - The occurrence of Mycobacterium bovis infection in cattle herds during the period 1966-92 in two geographically related areas in South-West England is compared. In one area comprising 104 km2 all badgers were systematically destroyed from 1975 81, after which recolonization was allowed; in the other, comprising 116 km2, small scale, statutory badger removal operations were undertaken from 1975 onwards where specific herds were detected with M. bovis infection. In the area with total clearance, no further incidents with M. bovis isolation occurred from 1982-92. Survival analysis and proportional hazards regression indicated that the risk of herds being identified with infection was less once badgers had been cleared from their neighbourhood, whereas it was greater in herds with 50 or more animals, and once cattle in a herd had responded positively to the tuberculin skin test, even though infection with M. bovis was not confirmed subsequently. The study provides further evidence that badgers represent an important reservoir of M. bovis infection for cattle and that badger control is effective in reducing incidents of cattle infection with M. bovis if action is thorough and recolonization is prevented. PMID- 7867738 TI - Prevalence of Leptospira spp. in wild brown rats (Rattus norvegicus) on UK farms. AB - Wild brown rats (Rattus norvegicus) are frequently implicated in the carriage and spread of Leptospira spp. Wild brown rats (n = 259) were trapped from 11 UK farms and tested for Leptospira spp. using a number of diagnostic tests. The prevalence of leptospiral infection was low, but there was variation in the results obtained with the different diagnostic tests. Estimates of prevalence ranged between 0% by silver-staining of tissues, 1% by the microscopic agglutination test, 4% by the enzyme-linked immunosorbent assay, 4% by culture, and 8% by fluorescent antibody technique. In total, 37 (14%) rats were positive by at least one of the tests, which contrasts with the frequently reported prevalences of 50-70% for wild rats in the UK. Serovar bratislava was a prevalent as icterohaemorrhagiae, although it was present only on farms with larger rat populations. PMID- 7867739 TI - Genome variation in the SAT types of foot-and-mouth disease viruses prevalent in buffalo (Syncerus caffer) in the Kruger National Park and other regions of southern Africa, 1986-93. AB - Dideoxy nucleotide sequencing of a portion of the 1D gene of SAT-type foot-and mouth disease viruses (FMDV) was used to derive phylogenetic relationships between viruses recovered from the oesophageo-pharyngeal secretions of buffalo in the Kruger National Park as well as several other wildlife areas in southern Africa. The three serotypes differed from one another by more than 40% while intratypic variation did not exceed 29%. Within each type, isolates from particular countries were more closely related to one another than to isolates from other countries lending credence to previous observations that FMDV evolve independently in different regions of the subcontinent. PMID- 7867740 TI - An investigation of possible routes of transmission of lumpy skin disease virus (Neethling). AB - British cattle were infected with the South African (Neethling) strain of lumpy skin disease virus (LSDV) and their clinical signs monitored over a 3-week period. Different routes of infection were assessed for effect on the clinical characteristics of the disease by using a clinical scoring system. Neither of 2 animals inoculated onto the conjunctival sac showed clinical signs of seroconverted. The intradermal route produced local lesions in 21 of 25 animals, and generalized infection in 4. In contrast the intravenous route produced generalized lesions in 8 of 11 animals. Seven uninfected animals were housed in contact with infected animals for 1 month. None developed clinical signs or produced detectable serum neutralizing antibodies. Six of seven of these animals were then challenged and were fully susceptible to infection. The results suggest that the transmission of LSDV between animals by contagion is extremely inefficient, and that parenteral inoculation of virus is required to establish infection. The high proportion of animals with generalized disease following intravenous inoculation implies that naturally occurring cases of generalized LSD may follow spread by intravenously feeding arthropods. PMID- 7867741 TI - The distribution of serotype-specific plasmids among different subgroups of strains of Salmonella enterica serotype Enteritidis: characterization of molecular variants by restriction enzyme fragmentation patterns. AB - Four hundred and thirty-four isolates of Salmonella enterica serotype Enteritidis were studied. They were grouped into five subsets defined by either the collection criteria or the parameter which formed the basis for subsequent analysis. Seventy-seven per cent harboured the serotype-specific plasmid (SSP). In 55% of the isolates this was the sole plasmid. Molecular variation in the SSP was detected in 17 (5%) of the isolates on the basis of restriction enzyme fragmentation pattern (REFP) analysis using Pst I and Sma I. The SSP variants were further characterized using additional restriction enzymes chosen to optimize the information content and analysed using a coefficient of similarity. A variant SSP designated pOG690 showed greater resemblance to the SSP of Salmonella enterica serotype Typhimurium than Enteritidis; 89% and 68% respectively for Pst I and 79% and 55% respectively for Sma I. In respect of the Pst I data pOG690 shared at least 55 kb of DNA with the Typhimurium SSP and 37 kb with the SSP of Enteritidis. This variant was associated with poultry (duck, goose, chicken) and all isolates belonged to phage type 9b. Other variants were associated with phage types 4, 6, 6a, 9a, 11, 15 and 24. The epidemiological implications of these results are discussed. PMID- 7867742 TI - Typhoid fever from water desalinized using reverse osmosis. AB - In May 1992, 81 bacteriologically confirmed cases of typhoid fever (TF) were identified in all districts of Tabuk City in northwestern Saudi Arabia. Attack rates (AR) in residential districts ranged from 0.9-10.3 per 10,000. Confirmed cases included 9 workers in the city's referral hospital, King Khalid Hospital (AR 140/10,000), 2 in families of medical staff, 57 in the community (AR 4.4/10,000) and 13 in a local military cantonment (AR 0.8/10,000). The outbreak began with the onset of TF in the three areas within 5 days, continued for 7 weeks, and ended 2 weeks after chlorination began. Among water sources, the odds ratio (OR) was highest (2.6; 95% confidence interval [CI] 1.25-5.39) for water purchased from reverse osmosis (RO) plants, especially RO plants supplied by one well (ASUW) (OR = 7.05; 95% CI 2.51-20.7). The aquifer for ASUW lay partially beneath a depression where city sewage collected. Unchlorinated water samples from ASUW 1 month after the outbreak ended yielded coliforms. ASUW probably became contaminated with Salmonella typhi when KKH demand overtaxed the aquifer and drew in surface water. Membranes in RO plants using this unchlorinated well water could then become fouled with S. typhi. RO plants, which are common throughout Saudi Arabia, need close monitoring. Water for RO must be prechlorinated to prevent microbiologic fouling of the membranes. PMID- 7867743 TI - Molecular characterization and antibiotic susceptibility of Vibrio cholerae non O1. AB - A collection of 64 clinical and environmental Vibrio cholerae non-O1 strains isolated in Asia and Peru were characterized by molecular methods and antibiotic susceptibility testing. All strains were resistant to at least 1 and 80% were resistant to two or more antibiotics. Several strains showed multiple antibiotic resistance (> or = three antibiotics). Plasmids most often of low molecular weight were found in 21/64 (33%) strains. The presence of plasmids did not correlate with antibiotic resistance or influence ribotype patterns. In colony hybridization studies 63/64 (98%) V. cholerae non-O1 strains were cholera toxin negative, whereas only strains recovered from patients were heat-stable enterotoxin positive. Forty-seven Bgl I ribotypes were observed. No correlation was shown between ribotype and toxin gene status. Ribotype similarity was compared by cluster analysis and two main groups of 13 and 34 ribotypes was found. Ribotyping is apparently a useful epidemiological tool in investigations of V. cholerae non-O1 infections. PMID- 7867744 TI - Distribution and virulence of Vibrio cholerae belonging to serogroups other than O1 and O139: a nationwide survey. AB - The distribution and virulence of Vibrio cholerae serogroups other than O1 and O139 in India before, during and after the advent of O139 serogroup was investigated. A total of 68 strains belonging to 31 different 'O' serogroups were identified during the study period. With the exception of O53, there was no spatial or temporal clustering of any particular non-O1 non-O139 serogroup at any given place. Two of the 68 strains examined produced cholera toxin (CT) which could only be partially absorbed with anti-CT immunoglobulin G. Tissue culture assay revealed that some of the non-O1 non-O139 strains produced factors which evoked either a cell rounding or cell elongation response depending upon the medium used. This study indicates that serogroups other than O1 and O139 should also be continuously monitored. PMID- 7867745 TI - Vibrio cholerae O139 in Thailand in 1994. AB - Vibrio cholerae O139 first appeared in India and Bangladesh in 1992. Surveillance for O139 was started at three hospitals in Thailand in 1993. By 1994 all three hospitals surveyed in Thailand had experienced an increase in Vibrio cholerae O139 infections. PMID- 7867746 TI - Meningococcal meningitis and carriage in western Zaire: a hypoendemic zone related to climate? AB - An analysis of bacteria recovered from cerebrospinal fluid over a 16-year period at a rural hospital in western Zaire showed that Neisseria meningitidis accounted for only five (2.2%) isolates. A survey of naso-pharyngeal colonisation with N. meningitidis in 378 healthy children was undertaken to distinguish whether this low frequency was due to lack of carriage or, by inference, lack of the co factors necessary to permit invasive disease. N. meningitidis was recovered from only three (0.78%) of the children. All isolates were non-typable strains of low pathogenicity. A review of studies examining the aetiology of bacterial meningitis and the geographical location of epidemics of meningococcal meningitis in and around Zaire reveals a 'hypoendemic zone', the limits of which correlate well with the area in which mean absolute humidity remains above 10 g m-3 of air throughout the year. Continuous high absolute humidity appears to reduce the transmission of meningococci. PMID- 7867747 TI - Incidence and spread of Haemophilus influenzae on an Antarctic base determined using the polymerase chain reaction. AB - A PCR-based method of detecting Haemophilus influenzae in cultures inoculated from throat swabs was evaluated using samples from groups of laboratory staff and medical students and then applied to samples originating from the closed human community of an Antarctic research station. Suitable PCR primers to an H. influenzae gene (ompP2) were used to amplify the gene from DNA preparations made from mixed growth on chocolate agar with added vancomycin. PCR product was reamplified and subjected to restriction endonuclease digestion to allow temporal and spatial mapping of strains over an 8-month period. Eleven different strains of H. influenzae were detected. One particular strain was detected in a third of the base members. PMID- 7867748 TI - Upregulation of nerve growth factor following cortical trauma. AB - As part of the inflammatory response to brain injury, CSF and tissue levels of interleukin-1 beta (IL-1 beta) are elevated after trauma. This elevation in IL-1 beta initiates a cascade of events among which may be an upregulation in nerve growth factor (NGF) in brain tissue. We infused IL-1 beta into the ventricle of adult rats and found a two- to fourfold increase in NGF in the cerebral cortex, hippocampus, and cerebellum, suggesting that IL-1 beta induced in vivo may also increase NGF in the brain. To test this hypothesis we utilized two models of traumatic brain injury (TBI) in the rat and examined NGF protein and RNA in the cortex over a period of several days. Both weight drop and controlled cortical contusion models of CNS trauma demonstrated large and significant increases in NGF protein in the cortex. NGF RNA was assessed in the controlled cortical contusion model and increased approximately fivefold by 1 day post-trauma. The remarkable elevation of NGF observed following TBI suggests that its role in response to injury may be other than as a target-derived growth substance. We hypothesize that the elevation of NGF in trauma induces upregulation of enzymes which suppress free-radical formation after injury. PMID- 7867749 TI - Loss of developing cholinergic basal forebrain neurons following excitotoxic lesions of the hippocampus: rescue by neurotrophins. AB - Previous studies have demonstrated that the viability of developing cholinergic basal forebrain neurons is dependent upon the integrity of neurotrophin-secreting target cells. In the present study, we examined whether infusions of nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) could prevent the loss of cholinergic septal/diagonal band neurons following excitotoxic lesions of their target neurons within the hippocampus. Postnatal Day 10 rat pups received unilateral intrahippocampal injections of ibotenic acid. Rats then received intracerebroventricular (icv) injections of nerve growth factor (30 micrograms/injection), brain-derived neurotrophic factor (60 micrograms/injection), or saline immediately following the lesion and continuing every third day for 27 days. Both saline- and BNDF-treated rats displayed a significant loss of septal/diagonal band neurons expressing the protein and mRNA for choline acetyltransferase (ChAT) and p75 low-affinity nerve growth factor receptor ipsilateral to the lesion. The magnitude of this loss was significantly attenuated in BNDF-treated rats. Many remaining neurons were atrophic with stunted dendritic processes. In contrast, NGF treatment completely rescued these cells and prevented the shrinkage of remaining cholinergic septal neurons. In addition, both NGF and BDNF induced a sprouting of cholinergic processes within the residual hippocampal remnant ipsilateral to the infusions. The present study demonstrates that icv injections of NGF, and to a lesser extent BDNF, prevent the loss of developing basal forebrain neurons which occurs following removal of normal target cells. Diffusion studies revealed relatively poor penetration of BDNF into brain parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867750 TI - Overlapping and additive effects of neurotrophins and CNTF on cultured human spinal cord neurons. AB - Ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) have been shown both in vitro and in vivo to support the survival and differentiation of developing chick or rat motoneurons. To explore the potential use of these and other neurotrophic factors as therapeutic agents in human motoneuron diseases, we have examined the effects of the neurotrophins NGF, BDNF, neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5) and the cytokines CNTF and cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF) and combinations of these factors on fetal human spinal cord neurons grown for 7-10 days in monolayer cultures. The level of choline acetyltransferase (ChAT) was determined in cultures grown in the presence of NGF, BDNF, NT-3, NT-4/5, CNTF, or CDF/LIF or with combinations of these factors. With the exception of NGF, each of these factors alone increased ChAT activity by two- to three-fold above control levels; combinations of NT-3 and CNTF were greater than either alone. As a single factor NT-4/5 produced the greatest increase in ChAT activity, but was not additive with any other neurotrophin or CNTF. A combination of the three factors CNTF, BDNF, and NT-3 or the four factors CNTF, BDNF, NT-3, and NT-4 increased ChAT levels by four-fold, an effect greater than any individual factor. The finding that combinations of these factors show some additive effects toward human spinal cord cholinergic neurons in culture has prompted the testing of such combinations in animal models of motoneuron disease. PMID- 7867751 TI - Operant conditioning of spinal stretch reflexes in patients with spinal cord injuries. AB - Hyperactive spinal stretch reflexes (SSRs) often occur with spinal cord injuries (SCI). These altered SSRs may impair movement. Recent studies in monkeys and human subjects have indicated that the magnitude of SSRs can be modulated using operant conditioning. The purpose of this study was to determine whether hyperactive biceps brachii SSRs could be operantly conditioned downward. Seventeen chronic (> 1 year postlesion) spinal cord-injured patients participated. Subjects were trained to keep biceps background (prestretch) electromyographic (EMG) activity and elbow angle at predetermined levels prior to having the elbow rapidly extended by a torque motor to elicit the biceps SSR. All subjects participated in six baseline sessions over a 2-week period. Then, subjects were randomly assigned to either control or training groups for the next 24 sessions over an 8-week period. By the end of the study, training subjects had significantly reduced biceps SSRs (t test, P < 0.001), while control subjects SSRs were not significantly reduced (t test, P > 0.05). The reduced SSRs persisted for up to 4 months following cessation of training. The results of this study support the hypothesis that hyperactive SSRs can be operantly conditioned downward in SCI patients. PMID- 7867752 TI - Calbindin-D28k immunoreactivity within the cholinergic and GABAergic projection neurons of the basal forebrain. AB - The purpose of this study was to determine whether the calcium binding protein calbindin-D28k was present within the cortically projecting basal forebrain neurons of various rodent species not previously examined. Double-label immunocytochemistry was performed using antibodies against calbindin-D28k and choline acetyltransferase (ChAT) to detect the presence of the calcium binding protein within the cholinergic basal forebrain neurons of various species (i.e., humans, rats, mice, gerbils, guinea pigs). Antibodies against calbindin-D28k, ChAT, and glutamic acid decarboxylase (GAD) were also used in combination with a cortically injected retrograde tracer (Fluoro-Gold) to determine whether calbindin-D28k immunoreactive (IR) neurons within the basal forebrain projected to the frontoparietal cortex. The nucleus basalis of rats was examined for the presence of calbindin-D27k IR within the GABAergic basal forebrain neurons. All species examined had cholinergic, GABAergic, and calbindinergic neurons within the basal forebrain; however, only the cholinergic neurons within the human nucleus basalis of Meynert were also immunoreactive for calbindin-D28k. Although all rodent species had both cholinergic and GABAergic basal forebrain neurons that contained the Fluoro-Gold dye, none of the calbindin-D28k IR neurons, detected using monoclonal and polyclonal antibodies, were found to contain the retrograde tracer. These results indicate that the cortically projecting cholinergic and GABAergic basal forebrain neurons within these rodent species do not contain calbindin-D28k. Therefore, age- and disease-related loss of nucleus basalis projection neurons may not be mediated by alterations in calbindin D28k.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867753 TI - Expression of low affinity NGF (p75) receptors in rat superior colliculus: studies in vivo, in vitro, and in fetal tectal grafts. AB - The distribution and level of expression of the low affinity nerve growth factor receptor (LNGFR) in the rat visual system has been investigated under a number of experimental conditions. The aim was to determine the cellular location of the receptor and to study the factors which influence its expression. The monoclonal antibody 192-Ig and immunohistochemical techniques were used to examine LNGFR expression in (i) developing and adult rat superior colliculus (SC), (ii) fetal collicular tissue transplanted to the midbrain of newborn host rats, (iii) the SC of rats which had been unilaterally enucleated at birth, and (iv) mixed glial cell cultures from the neonatal SC. The effect of eye removal on LNGFR immunoreactivity in other normally retino-recipient areas was also assessed. Postnatal maturation of the rat SC was associated with an increase in LNGFR immunoreactivity. At birth, weak staining was seen ventral to the superficial gray layer. Staining gradually became located more dorsally until in the adult there was a dense band of immunoreactivity that extended 50-100 microns from the surface. Immunoreactive processes and cellular-like profiles were seen. Compared to adult host SC there was considerably more LNGFR immunoreactivity in transplanted tectal tissue, irrespective of whether the grafts were connected to the host. LNGFR expression in transplants was patchy and usually contiguous with the graft surface. Staining was not obviously related to the distribution of astrocytes or microglia and very few cells were LNGFR positive in tectal glial cell cultures. In SC and in tectal grafts it is probable that LNGFR immunoreactivity was primarily associated with intrinsic neurons. In support of this, LNGFR expression in the superficial SC was unaffected by neonatal eye removal; however, LNGFR staining in the pretectum and diencephalon was reduced or absent on the side contralateral to visual deafferentation. These conflicting sets of data suggest that (i) LNGFRs in central visual pathways are sometimes, but by no means always, associated with retinal innervation and (ii) LNGFR expression in visual target areas originates from diverse sources and is influenced and regulated by a variety of factors. PMID- 7867754 TI - Morphological correlates of circadian rhythm restoration induced by transplantation of the suprachiasmatic nucleus in hamsters. AB - A compelling body of evidence indicates that the suprachiasmatic nucleus (SCN) of the hypothalamus is a pacemaker in the rodent circadian timing system. Two important components of this evidence are studies showing that SCN lesions abolish circadian rhythms and others demonstrating restoration of circadian activity rhythms after transplantation of fetal SCN into the brains of arrhythmic hosts. In the present study, we evaluated what has remained a persisting issue in this transplant literature, the extent to which the exact localization and organization of the transplants is critical to their capacity to restore circadian function in the hamster. The data obtained indicate that the location of the graft in the ventricular system is not crucial to outcome. Grafts in the lateral ventricle, dorsal third ventricle, interventricular foramen, and caudal third ventricle are as capable of restoring circadian function as ones placed in the ventral third ventricle in the vicinity of the lesion. Restoration of rhythmicity does require that the grafts contain a minimum volume of SCN-like tissue as defined by cytoarchitecture and the presence of vasopressin--and vasoactive intestinal polypeptide (VIP)--immunoreactive cells and fibers. There is also an indication that VIP-immunoreactive elements are the component critical to functional recovery. Connections between graft and host are evident in the immunohistochemical material but are quite variable in extent and often very limited. Thus, the data obtained in this study are consistent with the view that restoration of circadian function by fetal grafts requires the presence of SCN, and probably VIP-containing neurons, but does not depend upon the exact location of the graft or the presence of specific connections between graft and host. PMID- 7867755 TI - Chronic treatment with levodopa and/or selegiline does not affect behavioral recovery induced by fetal ventral mesencephalic grafts in unilaterally 6 hydroxydopamine-lesioned rats. AB - It has been suggested that levodopa (L-dopa), a dopamine precursor used to treat Parkinson's disease, may be toxic to grafted fetal neuroblasts; if so, the use of the monoamine oxidase B inhibitor selegiline might prevent such toxicity. We randomly assigned 30 unilaterally 6-hydroxydopamine-lesioned male Sprague-Dawley rats, whose lesions were verified with low-dose apomorphine-induced rotations, to one of five treatment groups: (i) L-dopa methyl ester (125 mg/kg/day) with benserazide (a peripheral decarboxylase inhibitor; 25 mg/kg/day), (ii) L-dopa methyl ester with benserazide and selegiline (L-deprenyl; 0.5 mg/kg/day), (iii) selegiline only, (iv) and (v) vehicle (ascorbate in normal saline) only. After 2 weeks of twice-daily ip injections, the rats received fetal ventral mesencephalic grafts into the lesioned striatum; one vehicle group received sham grafts. Drug therapy was continued for 2 1/2 months post grafting. At 1 month after grafting, and every 2 weeks thereafter, the rats were tested using low-dose apomorphine induced rotation. A 70% decrease in rotations among all grafted groups, relative to the shams, was found. No statistical differences among groups receiving various drug therapies were seen in behavior or in counts or dimensions of tyrosine hydroxylase-positive cells. We therefore conclude that, in the unilaterally lesioned rat model of Parkinson's disease, there is no adverse effect of L-dopa nor any significant effect of selegiline, either alone or coadministered with L-dopa, on behavioral recovery induced by fetal ventral mesencephalic grafts. PMID- 7867756 TI - Biochemical and immunocytochemical changes induced by intrastriatal 6 hydroxydopamine injection in the rat nigrostriatal dopamine neuron system: evidence for cell death in the substantia nigra. AB - Biochemical and immunocytochemical changes after unilateral 6-hydroxydopamine (6 OHDA) injection into the striatum were investigated in the rat nigrostriatal dopamine (DA) neuron system. Four weeks after 6-OHDA injection into the striatum, concentrations of DA and its metabolites were specifically decreased in the substantia nigra (SN), as well as in the striatum, ipsilateral to the injection. Immunocytochemistry of tyrosine hydroxylase (TH) revealed a marked decrease in the number of TH-immunoreactive neuronal cell bodies in the SN ipsilateral to the injection; this effect appeared 2 weeks after the injection and remained even 10 months after the injection. Electron microscopic study of these periods demonstrated degenerative neurons in the SN pars compacta, suggesting that the degenerative changes persisted for a long time after a single injection of 6-OHDA into the striatum. The results showed that degeneration of the dopaminergic terminals in the striatum may lead to cell death of the parent cell bodies in the SN and suggest that the striatum may be the initial site in which the neurodegeneration occurs in Parkinson's disease. PMID- 7867757 TI - Cholecystokinin facilitates methamphetamine-induced dopamine overflow in rat striatum and fetal ventral mesencephalic grafts. AB - The purpose of this study was to investigate the interactions of sulfated (S) and unsulfated (US) cholecystokinin (CCK) and methamphetamine (MA)-induced dopamine (DA) overflow in rat striatum. High-speed chronoamperometric recording techniques, using Nafion-coated carbon fiber electrodes, were used to evaluate extracellular DA concentration. CCK-8S, CCK-8US, MA, and DA were locally applied directly to the striatum of urethane-anesthetized Sprague-Dawley rats. We found that CCK potentiated MA-induced DA release in the anterior striatum. This response is probably mediated through CCK-A receptors because CCK-8S, but not CCK 8US, enhanced MA-induced responses. Replacement of Ca2+ with Mg2+ in the drug barrel antagonized this reaction, suggesting that the modulation of MA-induced DA release by CCK is Ca2+ dependent. Both MA-induced DA release and CCK modulatory effects disappeared in the striatum after unilaterally lesioning the medial forebrain boundle with 6-hydroxydopamine (6-OHDA). We had previously found that the zone of normalized dopamine clearance in 6-OHDA-lesioned rats was considerably larger than that of normalized release in the anterior striatum after fetal ventral mesencephalic (VM) transplantation, which may be a result of partial reinnervation from the transplant. In the present study, we found that the modulation of DA release by CCK was restored only in the zone of normalized release after fetal nigral transplantation; CCK did not increase MA-induced DA release throughout the larger partially innervated area. In conclusion, these findings suggest that not only DA release processes but also CCK modulatory mechanisms are restored in the anterior striatum after fetal VM transplantation. PMID- 7867758 TI - The effects of haloperidol on dopamine receptor gene expression. AB - Haloperidol is a widely prescribed antipsychotic that acts as a dopamine D2 receptor antagonist. Chronic administration of haloperidol leads to an increase in striatal D2 receptor binding; however, studies examining striatal D2 receptor mRNA after haloperidol treatment report inconsistent results. This study examines the effects of haloperidol on dopaminoceptive striatal neurons, as well as dopamine D2 containing striatal inputs. Rats were injected subcutaneously with 2 mg/kg haloperidol twice daily for 7 days. A significant (36%) increase in D2 mRNA was observed in the anterior cingulate cortex. However, no changes were observed in the amounts of D1, D2, D3 mRNA, or D2 heteronuclear RNA (hnRNA) in the striatum or in the levels of D2 mRNA and hnRNA in the substantia nigra and ventral tegmental area. Thus, increased striatal D2 binding after haloperidol treatment may not be the result of altered D2 gene activity in the striatum or midbrain, but could result from an increase in D2 mRNA in cingulate corticostriatal neurons and/or a longer half-life for the D2 receptor protein in striatal neurons. Striatal proenkephalin mRNA increased significantly in the caudate-putamen (45%), nucleus accumbens (36%), and the olfactory tubercle (27%) while prodynorphin mRNA remained unaltered after haloperidol treatment. Since D2 receptor mRNA is generally colocalized with proenkephalin mRNA in striatal neurons, these results demonstrate what is likely a selective cellular increase in proenkephalin mRNA without a parallel increase in D2 mRNA. PMID- 7867759 TI - Dopaminergic regulation of a transfected preproenkephalin promoter in primary rat astrocytes in vitro and in vivo. AB - The clinical benefit of transplantation therapies utilizing genetically modified cells could be enhanced if expression of engineered genes was regulated by clinically useful pharmacological agents. Toward this end, we examined pharmacologic effects on the expression of hybrid gene constructs transfected into primary rat striatal astrocytes. These astrocytes are known to express receptors for the neurotransmitter dopamine (DA). In vitro, we found that expression of a transiently transfected human ppEnk promoter-driven chloramphenicol acetyltransferase (CAT) reporter construct was induced by DAergic agonists, as much as 20-fold. This induction was blocked by a DA receptor antagonist. The same concentration of DA also increased the endogenous rat ppEnk mRNA, by > 2-fold. In vivo, regulation of CAT expression by DA was tested by implanting the genetically modified astrocytes into the normal striatum and the contralateral striatum which had > 95% DA depletion induced by a previous 6 hydroxy-DA lesion of the substantia nigra. As hypothesized on the basis of the in vitro data, CAT activity on the lesioned side, where the stimulating effect of endogenous DA was lacking, was 30% lower than on the control side where the normal DA content was present. The data suggest that control of the enkephalin gene in astrocytes may involve second messenger pathways activated by DA receptors. Moreover, the evidence that clinically applicable drugs can regulate inducible genes introduced into the brain by astrocyte implantation is of potential importance in development of therapeutic strategies. PMID- 7867760 TI - Plaque-associated neuronal proteins: a recurrent motif in neuritic amyloid deposits throughout diverse cortical areas of the Alzheimer's disease brain. AB - Diffuse and neuritic plaques are sites of accumulation of beta-amyloid peptides (A beta) in the brains of Alzheimer's disease (AD) patients. Although amyloid fibrils are formed from A beta, the contribution of other plaque-associated proteins and peptides to the pathogenesis of AD amyloidosis is unknown. To pursue this issue, we sought to identify proteins and peptides that were consistently associated with neuritic plaques in six different cortical areas of AD and control brains. We accomplished this by using quantitative, single and double label immunohistochemistry and a panel of antibodies to proteins or peptides that are known to be associated with neuritic plaques in the AD hippocampus. Our data showed that the molecular composition of neuritic plaques in association, limbic, sensory, and motor cortex was similar regardless of the type of cortex in which they were found or the apolipoprotein E genotype of the patient. Further, proteins and peptides associated with neuritic plaques in the cortical areas of the AD brain studied here were similar to those found in neuritic plaques of the AD hippocampus. Specifically, in addition to A beta 1-40 and A beta 1-42, these plaques contained immunoreactivity for other domains in A beta precursor proteins, neurofilament and tau proteins, as well as phosphotyrosine residues. We conclude that the recurrent association of a distinct group of neuronal and other proteins and peptides with neuritic plaques suggests that these plaque-associated components play a mechanistic role in the pathogenesis of amyloidosis in AD. PMID- 7867762 TI - Transient reinnervation of antagonistic muscles by the same motoneuron. AB - When reinnervation is allowed after a sciatic nerve cut in the adult rat, motoneuron axons may branch to innervate antagonistic muscles. This multiple innervation is widespread, but transient. Fourteen weeks after denervation isometric muscle contraction experiments and studies with anterograde transport of the fluorescent tracer Fast Blue showed that branches from the same motoneurons reached the distal part of the tibial nerve and either the soleus or the extensor digitorum longus muscles or both muscles. Retrogradely double labeled motoneurons were found after injections of different fluorescent tracers into these muscles. Sixty-four to 88 weeks after the nerve cut, similar experiments showed that selective innervation was reestablished. The findings suggest a selective mechanism for axon withdrawal in an adult mammal. PMID- 7867761 TI - Polyamine effects on the NMDA receptor in human brain. AB - Polyamines are thought to modulate the activation of NMDA receptors through a unique allosteric regulatory site. The effects of polyamines on the binding of [3H]MK-801 were measured in cortical and hippocampal tissue surgically removed from patients with temporal lobe epilepsy (TLE). The polyamine agonist spermidine increased the binding of [3H]MK-801 in the cortex in a dose-dependent manner and this effect could be blocked by the weak partial agonist diethylenetriamine (DET). Spermidine decreased the Kd of [3H]MK-801 for the NMDA receptor but did not alter the density of receptors. Spermidine had essentially the same effect on Kd and Bmax measured in the dentate gyrus of TLE subjects and the cortex and dentate gyrus of postmortem controls. Moreover, there was no difference in the density of binding sites between postmortem and TLE subjects in either region. The binding of [3H]MK-801 in human cortex was decreased by 30% by incubation with DET or by prewashing the tissue sections. In contrast, DET did not alter the binding of [3H]MK-801 in rat cortex and prewashing sections produced an increase rather than a decrease in binding. These results suggest that there are different endogenous modulators for the polyamine site in rat and human tissue. The inverse agonist 1,10-diaminodecane decreased the binding of [3H]MK-801 in a dose dependent manner. These results suggest that the fundamental modulatory properties of polyamines in rat and human tissues are essentially the same and that endogenous polyamines may regulate human NMDA receptors. PMID- 7867763 TI - Intrathecal administration of dizocilpine maleate (MK-801) attenuates ischemic damage in the rabbit spinal cord. AB - The therapeutic efficacy of intrathecally administered MK-801 (dizocilpine maleate), a noncompetitive receptor antagonist of N-methyl-D-aspartate receptor complex, was investigated in a rabbit spinal cord ischemia model. Normal saline, 0.3 ml (control, n = 4) or MK-801, 150 micrograms in 0.3 ml of saline, was administered intrathecally at the level of the lumbar enlargement, 30 min before (pretreatment, n = 7) or in the first min after (post-treatment, n = 4) 30 min of aortic occlusion followed by 2-h reperfusion. Nauta silver method was used for histopathological evaluation of lumbosacral segments. The degree of gray matter damage (argyrophilic neurons) was evaluated in three areas: A1, Rexed's laminae I VI; A2, laminae VII and X; and A3, laminae VIII-IX. Pre- and post-treatment with MK-801 decreased the number of argyrophilic neurons (P < 0.05) in all areas examined. The number of argyrophilic neurons in A1, A2, and A3 was reduced by 59, 28, and 29%, respectively, by MK-801 pretreatment and by 87, 66, and 46%, respectively, by MK-801 post-treatment. Our results show that with single bolus intrathecal administration the efficacy of MK-801 was greater with post- compared to pretreatment and most dramatic in Rexed's laminae I-VI compared to laminae VII X. Intrathecal administration of MK-801 prior to or at the beginning of the recirculation diminishes the extent of postischemic neuronal spinal cord damage at early postreperfusion period. PMID- 7867764 TI - NMDA and not non-NMDA receptor antagonists are protective against seizures induced by homocysteine in neonatal rats. AB - Homocysteine induces seizures in adult, as well as in immature, experimental animals, but the mechanism of its action is still unknown. The aim of the present study was to examine whether homocysteine in immature animals may act via excitatory amino acids receptors. Seizures were induced in 7-day-old rats by ip administration of homocysteine (16.5 mmol/kg) and the effects of selected antagonists at NMDA and non-NMDA receptor sites were investigated. The anticonvulsant effect was evaluated not only in terms of behavioral changes, but also in terms of some indicators of brain energy metabolism. Rat pups were sacrificed during generalized clonic-tonic seizures, corresponding approximately to 15-30 min after homocysteine administration. Comparable time intervals were used for sacrificing pups in the groups with protective drugs. Non-NMDA antagonists, L-glutamic acid diethylester (GDEE) (4 mmol/kg, ip) and 2,3 dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline (NBQX) (two doses, 30 mg/kg each, ip), failed to protect neonatal rats against homocysteine-induced seizures. Although NBQX prevented the tonic phase, the severity of clonic movements was even more pronounced. Metabolic changes accompanying the seizures (decreases of glucose and glycogen and a rise of lactate) were also not influenced by GDEE or NBQX pretreatment. On the contrary, NMDA antagonists, both competitive (AP7, 0.33 mmol/kg, ip) and noncompetitive (MK-801, 0.5 mg/kg, ip), had a clear-cut anticonvulsant effect. They not only suppressed the behavioral signs of seizures, but also prevented most of the metabolic changes accompanying seizures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867765 TI - Seizure development and noradrenaline release in kindling epilepsy after noradrenergic reinnervation of the subcortically deafferented hippocampus by superior cervical ganglion or fetal locus coeruleus grafts. AB - Solid pieces of fetal locus coeruleus (LC) or superior cervical ganglion (SCG) were placed into a fimbria-fornix lesion cavity in 6-hydroxydopamine-treated, noradrenaline (NA)-denervated rats. Six to 8 months later, all animals were subjected to electrical kindling stimulations in the hippocampus until they had reached the fully kindled state. Nongrafted lesioned animals showed markedly increased kindling rate which was partly attenuated by LC but not SCG grafts. In both LC- and SCG-grafted animals, dopamine beta-hydroxylase immunocytochemistry demonstrated a high density of graft-derived noradrenergic fibers in the dorsal hippocampus, whereas reinnervation of the ventral hippocampus was much more sparse. Subregional distribution of these fibers within the hippocampus was different in the two grafted groups. Both grafts partly restored basal extracellular NA levels in the hippocampus and reacted to generalized seizures by a significant (two- to threefold) increase of NA release, as measured by intracerebral microdialysis. Our data indicate (i) that seizure activity can regulate transmitter release from noradrenergic neurons in both LC and SCG grafts, (ii) that only fetal LC grafts retard seizure development in kindling, and (iii) that the inability of SCG implants to influence kindling epileptogenesis could be due to a lack of synaptic contacts between the graft derived ganglionic fibers and host hippocampal neurons. PMID- 7867766 TI - The interleukin-1 receptor antagonist (rhIL-1ra) protects against cerebral infarction in a rat model of hypoxia-ischemia. AB - We assessed the cerebral protective effects of the competitive interleukin-1 antagonist rhIL-1ra in 7-day-old rats that were subjected to brain hypoxia ischemia by unilateral carotid artery ligation and subsequent exposure to 2 h of 7.5% O2-balanced N2. This procedure leads to atrophy in the cerebral hemisphere ipsilateral to carotid occlusion, with prominent foci of neuronal infarction in the striatum. Systemic administration of 100 mg/kg of rhIL-1ra before and/or after the hypoxic exposure limited the insult. The results indicate that rhIL-1ra has potent neuroprotective properties against morphologic brain injury from hypoxia-ischemia. rhIL-1ra may prove to be clinically useful in protecting against hypoxia-ischemia-related disorders. PMID- 7867767 TI - Tumor suppressor p53 induction and DNA damage in hippocampal granule cells after adrenalectomy. AB - Tumor suppressor p53 encodes a protein that is an important regulator of the cell cycle. However, under certain conditions increased p53 expression results in programmed cell death or apoptosis. We used in situ hybridization histochemistry to investigate the role of p53 in the adrenalectomy-induced degeneration of hippocampal granule cells. Three days after adrenalectomy, a subpopulation of granule cells exhibiting morphological features of apoptosis expressed increased amounts of p53 mRNA. Both adrenalectomy-induced p53 expression and granule cell degeneration were prevented by daily administration of corticosterone. In situ end-labeling of nuclei containing fragmented DNA revealed a distribution similar to that of cells with increased p53 expression. These results demonstrate an association between p53 induction and apoptosis in the central nervous system and support the idea that cell cycle-related genes play a role in neuronal death pathways. PMID- 7867769 TI - Prion protein gene expression in cultured astrocytes treated by recombinant growth hormone and insulin-like growth factor. AB - Cases of Creutzfeldt-Jakob disease recently occurred after long treatments with pituitary extracted human growth hormone (GH). Prion protein (PrP) and glial fibrillary acidic protein (GFAP), an astrocyte-specific marker, both accumulate in the central nervous systems of infected individuals during transmissible subacute spongiform encephalopathies (TSSE). PrP expression has been linked to susceptibility to and development of these diseases. We have investigated the effects of recombinant growth hormone, its main biological effector, insulin-like growth factor 1 (IGF-1), and two well known mitogens, epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), on PrP and GFAP mRNA levels in primary cultures of murine astrocytes using Northern blot quantitation. After 48 h of exposure to these soluble factors, PrP mRNA levels remained unchanged relative to controls in all growth factor-treated cultures, whereas GFAP mRNA concentrations decreased markedly in EGF- and bFGF-treated cultures. These results suggest that GH and IGF-1 do not modulate PrP gene expression in astrocytes. PMID- 7867768 TI - Multiple astrocyte transcripts encode nigral trophic factors in rat and human. AB - The recent discovery of glial cell line-derived neurotrophic factor (GDNF) identified a novel trophin that selectively increases survival of substantia nigra dopaminergic neurons, which degenerate in Parkinson's disease. Our previous studies indicated that GDNF RNA can be amplified from cultured rat nigral type 1 astrocytes and from rat striatum in vivo, implying local as well as target trophic support. The current study establishes the regional pattern of GDNF RNA expression in adult human brain. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed the highest expression of GDNF mRNA in the human caudate, with low levels in the putamen and no detectable message in the nigra, suggesting that GDNF is a target-derived factor in humans. We also report the isolation of two additional GDNF-related cDNAs, termed astrocyte-derived trophic factors (ATF), which apparently result from differential RNA processing. Sequence analysis of rat ATF-1 revealed a 78-bp deletion corresponding to a loss of 26 amino acids within the prepro region of the predicted GDNF protein. The RNA processing events responsible for ATF-1 formation in rat brain are conserved in humans; we report the isolation of a full-length human ATF-1 homologue. We identified a second alternative transcript, human ATF-2; the transcript encodes a protein which differs in its first 18 amino acids from the predicted mature GDNF and ATF-1 proteins and shares the terminal 115 residues with the other two forms. To begin assessing the biologic significance of multiple transcript expression we characterized the actions of COS-expressed GDNF and ATF-1 cDNAs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867770 TI - Nonpermissive nature of fish optic nerves to axonal growth is due to presence of myelin-associated growth inhibitors. AB - Fish optic nerve sections were recently shown to be nonpermissive to growth of adult retinal axons. In addition, fish optic nerve myelin was found to inhibit growth of adult retinal axons and this inhibition was neutralized by IN-1 antibodies (known to block rat myelin-associated inhibitors). In this study we examined whether the growth nonpermissiveness of fish optic nerves which had not been injured prior to their excision results, at least in part, from the presence of myelin-associated growth inhibitors. It was found that preincubation of the sections with IN-1 antibodies, known to recognize and neutralize the myelin associated growth inhibitors of the rat central nervous system, increases sixfold the number of axons that grow on these sections. This demonstrates that fish myelin-associated growth inhibitors, which are similar to those of rat, are at least partly responsible for the growth nonpermissiveness of normal fish optic nerves. PMID- 7867771 TI - The dynamics of young men's condom use during and across relationships. AB - According to data from the 1991 National Survey of Adolescent Males, condom use is likely to be highest at the beginning of relationships and to decline as the relationship continues. The proportion of sexually active men aged 17-22 who used a condom with their most recent partner declined from 53% the first time they had intercourse with that partner to 44% at the most recent episode. Condom use also decreases with age; 59% of 17-18-year-olds used a condom the first time they had intercourse with their most recent partner, compared with 56% of 19-20-year-olds and 46% of 21-22-year-olds. However, the probability that the female partner used the pill the first time that the couple had sex increased with the man's age- from 21% among 17-18-year-olds to 35% among 21-22-year-olds. Young men were more likely to have used a condom if they thought their partner was sexually inexperienced, and less likely to have done so if they suspected their partner was at high risk for an STD. PMID- 7867772 TI - Maternal marital status as a risk factor for infant mortality. AB - The increased risk of infant mortality associated with single motherhood is neither consistent among social and demographic subgroups nor inevitable, according to data from national linked birth and infant death files for 1983 1985. Maternal age is the only variable found to have a significant interaction with marital status among black mothers, and the risk associated with unmarried status increases with age. Among white mothers, age, educational level and receipt of prenatal care all show significant interactions with marital status; the increased risks of infant mortality attributed to unmarried motherhood are concentrated among subgroups usually thought to be at lower risk. For example, the risks of infant mortality among unmarried white women relative to married white women are highest among 25-29-year-olds. However, being unmarried did not affect the risk of infant mortality among babies born to college-educated white women. PMID- 7867773 TI - Sex, alcohol and sexually transmitted diseases: a national survey. AB - The analysis of a representative national survey of households provides strong evidence that alcohol overshadows illicit drug use as a risk factor for sexually transmitted diseases (STDs). Men and women who report a history of STDs are significantly more likely to have a history of problem drinking, independent of high-risk sexual activities and demographic characteristics. However, a high rate of change in sexual partners over the past five years also increases the chance of STD infection. Sexual orientation is a major STD risk factor among men but not among women. Although both black men and black women are at greater risk of STDs than are those in other racial or ethnic groups, results indicate that black women's greater likelihood of having sex with men who have multiple partners, rather than their own rates of partner change, makes the crucial difference between their risk and that of white women. PMID- 7867774 TI - Reproductive health and AIDS-related services for women: how well are they integrated? AB - To explore the relationship between human immunodeficiency virus (HIV) and AIDS services and reproductive health services, a survey was undertaken in 1994 of 30 health care facilities that are grantees under Title IIIb of the Ryan White Comprehensive AIDS Resource Emergency Act, 19 family planning clinics that offer at least some HIV services, and two family planning agencies that are also grantees under Title IIIb. The Title IIIb providers and the family planning agencies offer similar sets of services, but they tend to view reproductive health and HIV and STD services as distinctly different categories. Eliminating the perceptual distinctions between these services and viewing reproductive health services as key components of HIV and AIDS prevention could result in a more integrated system of helping women with HIV infection or AIDS as well as those at risk of HIV infection. PMID- 7867775 TI - How frequently is emergency contraception prescribed? AB - A 1993 survey of 294 reproductive health care providers, family practitioners and emergency room physicians investigated the frequency of prescribing emergency contraception. Hormonal emergency contraception had been prescribed by respondents an average of 3.4 times in the preceding 12 months. Almost one-third of the prescriptions were for rape victims, the majority written by emergency physicians. Fifteen IUD insertions for emergency contraception were performed in the preceding year. Few respondents had ever discussed emergency contraception with patients or had literature available on the topic. PMID- 7867776 TI - The Cairo consensus: population, development and women. PMID- 7867777 TI - Structure-function relationships of cation translocation by Ca(2+)- and Na+, K(+) ATPases studied by site-directed mutagenesis. AB - Site-directed mutagenesis studies of the sarcoplasmic reticulum Ca(2+)-ATPase have pinpointed five amino acid residues that are essential to Ca2+ occlusion, and these residues have been assigned to different parts of a Ca2+ binding pocket with channel-like structure. Three of the homologous Na+, K(+)-ATPase residues have been shown to be important for binding of cytoplasmic Na+ at transport sites. In addition, three of the above mentioned Ca(2+)-ATPase residues appear to participate in the countertransport of H+, and two of the Na+, K(+)-ATPase residues to participate in the countertransport of K+. Residues involved in energy transducing conformational changes have also been identified by mutagenesis. In the Ca(2+)-ATPase, ATP hydrolysis is uncoupled from Ca2+ transport following mutation of a tyrosine residue located at the top of transmembrane segment M5. This tyrosine, present also in the Na+, K(+)-ATPase, may play a critical role in closing the gate to a transmembrane channel. PMID- 7867778 TI - Location and properties of the digitalis receptor site in Na+/K(+)-ATPase. AB - Since 1985, several research groups have shown that a number of amino acids in the catalytic alpha-subunit of Na+/K(+)-ATPase more or less strongly modulate the affinity of a digitalis compound like ouabain to the enzyme. However, scrutiny of these findings by means of chimeric Na+/K(+)-ATPase constructs and monoclonal antibodies has recently revealed that the modulatory effect of most of these amino acids does not at all result from direct interaction with ouabain, but rather originates from long-range effects on the properties of the digitalis binding matrix. Starting from this knowledge, the present review brings together the various pieces of evidence pointing to the conclusion that the interface between two interacting alpha-subunits in the Na+/K(+)-ATPase protodimer (alpha beta)2 provides the cleft for inhibitory digitalis intercalation. PMID- 7867779 TI - New and specific nucleoside diphosphate glucose substrates for glycogenin. AB - Glycogenin, the autocatalytic, self-glucosylating primer for glycogen synthesis by glycogen synthase, is presumed, in vivo, to use UDP-glucose as the source of the glucose residues it adds to itself. When we tested its ability to utilize other nucleoside diphosphate glucoses, it emerged that purine nucleotides are not utilized but two pyrimidine nucleotides are used, in addition to UDP-glucose. These are CDP-glucose and TDP-glucose. CDP-glucose is utilized at 70% of the rate of UDP-glucose. While there is no evidence that CDP-glucose is a natural substrate for glycogenin, it has the advantage over UDP-glucose in that it can be used specifically to detect and assay glycogenin in the presence of glycogen synthase because CDP-glucose, unlike UDP-glucose, is not a substrate for the synthase. PMID- 7867780 TI - The three-dimensional solution structure of a constrained peptidomimetic in water and in chloroform. Observation of solvent induced hydrophobic cluster. AB - A large number of protein-protein interactions involved turn or loop regions. The excised linear peptides from these regions reveal complex conformational averaging. To circumvent this motional averaging and to stabilize the beta-turn conformation, extensive effort has been devoted to the design of constrained peptidomimetics. Here, we report the three-dimensional solution structure of a 12 membered cyclic peptidomimetic. The structures were calculated from NMR studies performed in chloroform and in water at 263 and 278K, respectively. This 12 membered cyclic scaffolding is part of a program to design and to construct conformationally stable beta-turn peptidomimetics. The impact of the surrounding environment on the conformation of this constrained peptidomimetic is discussed. The general structural features of the cyclic mimetic are retained in both environments; however, the formation of a hydrophobic patch in the aqueous solvent is evident. PMID- 7867781 TI - Differentiation-inducing factor of D. discoideum raises intracellular calcium concentration and suppresses cell growth in rat pancreatic AR42J cells. AB - DIF (differentiation-inducing factor) is a putative morphogen that induces stalk cell differentiation in the lower eukaryote, Dictyostelium discoideum. In this study, we have examined the effects of DIF on growth and the intracellular calcium concentration ([Ca2+]i) in rat pancreatic acinar AR42J cells. Growth of AR42J cells was inhibited when DIF was present in the media, and approximately 50% growth inhibition was attained with 20 microM DIF. DIF was also found to raise [Ca2+]i in a dose-dependent manner (1-40 microM), both in the presence and absence of extracellular Ca2+. These results suggest that DIF elicits both calcium influx from the extracellular space and calcium release from intracellular pool(s), thereby inhibiting cell growth in AR42J. PMID- 7867782 TI - GroES and the chaperonin-assisted protein folding cycle: GroES has no affinity for nucleotides. AB - The E. coli chaperonin proteins, GroEL and GroES, assist in folding newly synthesized proteins. GroES is necessary for GroEL-assisted folding under conditions where the substrate protein cannot spontaneously fold. On the basis of photolabelling of GroES with 8-azido-ATP, a role for nucleotide binding to GroES in chaperonin function was suggested [Martin, et al., Nature, 366 (1993) 279 282]. We confirm the photolabeling of GroES with 8-azido-ATP. However, other proteins not known to contain nucleotide binding sites also became photolabeled suggesting that labeling is non-specific. Using rigorous physical methods, isothermal calorimetry and equilibrium binding, no interaction between GroES and nucleotides could be detected. We conclude that GroES has no nucleotide binding site. PMID- 7867783 TI - The effect of iron status on glyceraldehyde 3-phosphate dehydrogenase expression in rat liver. AB - The influence of iron status on glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene transcription, mRNA levels and distribution was determined in whole liver samples from adult Wistar rats. While iron loading did not alter GAPDH expression, iron deficiency evoked a 2.3-fold increase in the steady-state level of liver GADPH mRNA, but did not affect gene transcription or intracellular localisation of the message. Therefore, the over-expression of GAPDH mRNA in iron deficiency is probably due to increased message stability. PMID- 7867784 TI - Cooperation of the molecular chaperone Ydj1 with specific Hsp70 homologs to suppress protein aggregation. AB - Ydj1p, a cytosolic DnaJ homolog from Saccharomyces cerevisiae, is demonstrated to function as a molecular chaperone. Purified Ydj1p formed complexes with non native polypeptides and suppressed protein aggregation. Ydj1p cooperated with Ssa Hsp70 proteins in the prevention of protein aggregation, but not with the Ssb Hsp70 proteins. Cooperation between these different molecular chaperones was only observed in the presence of hydrolyzable ATP and correlated with the ability of Ydj1p to stimulate the ATPase activity of the Hsp70 homolog with which it was paired. The regulatory and chaperone activities of a eukarytic DnaJ homolog thus act together to assist Hsp70 in modulating the conformation of proteins. PMID- 7867785 TI - The MAP kinase signal transduction pathway is activated by the endogenous cannabinoid anandamide. AB - Anandamide is an endogenous ligand for delta 9-tetrahydrocannabinol (THC) receptors. Incubation of cultured cells with anandamide or THC causes increased arachidonic acid release and eicosanoid biosynthesis. Here we demonstrate that the MAP kinase signal transduction pathway contributes to this response. Treatment of WI-38 fibroblasts with anandamide causes increased MAP kinase activity and increased phosphorylation of the arachidonate-specific cytoplasmic phospholipase A2 (cPLA2). Significantly, MAP kinase phosphorylates and activates cPLA2 [Lin, et al., Cell, 72 (1993) 269-278]. The MAP kinase signal transduction pathway may therefore mediate the effects of anadamide on cPLA2 activation and arachidonic acid release. PMID- 7867786 TI - Protein kinase C activator inhibits voltage-sensitive Ca2+ channels and catecholamine secretion in adrenal chromaffin cells. AB - We have investigated the effects of the phorbol ester 12-myristate 13-acetate (PMA) on depolarization-evoked Ca2+ influx and catecholamine secretion in bovine adrenal chromaffin cells. PMA (100 nM) strongly inhibited K(+)-evoked [Ca2+]i transients and Mn2+ quenching of fura-2 fluorescence. In contrast, 4 alpha phorbol 12,13-didecanoate, a phorbol ester inactive on protein kinase C (PKC), had no effect. Maximal PMA-mediated inhibition occurred at 5-10 min incubations and were variable from cell to cell, ranging from 25 to 65% of controls. The [Ca2+]i transients evoked by the L-type Ca2+ channel activator Bay K 8644 were strongly inhibited by 100 nM PMA. PMA (0.1-10 microM) inhibited K(+)-evoked adrenaline and noradrenaline release by 23-44%. The data indicate that phorbol ester-mediated activation of PKC inhibits voltage-sensitive Ca2+ channels in chromaffin cells, leading to a prominent depression of depolarization-evoked catecholamine secretion. PMID- 7867787 TI - Sodium butyrate inhibits expression of urokinase and its receptor mRNAs at both transcription and post-transcription levels in colon cancer cells. AB - The effects of butyrate on the modulation of urokinase plasminogen activator (uPA) and its receptor (uPAR) mRNAs were studied. While both mRNA levels were increased after stimulation by tumor necrosis factor alpha (TNF alpha), phorbol ester (PMA) and cycloheximide, they were inhibited by butyrate at 2.5 to 25 mM. Nuclear run-on transcription assays indicated that uPA mRNA was modulated by butyrate at the transcriptional level but the uPAR gene was regulated at both transcriptional and post-transcriptional levels in the presence or absence of TNF alpha. In the presence of PMA, however, butyrate acts at the post-transcriptional level on both genes. PMID- 7867788 TI - Low frequency MFs increased inositol 1,4,5-trisphosphate levels in the Jurkat cell line. AB - We have earlier reported that when a weak 50 Hz MF (magnetic field) was applied, the leukemic T-cell line Jurkat responded with intracellular calcium oscillations [Lindstrom, et al., J. Cell Physiol., 156 (1993) 395-398]. The result suggested that the MF interfered with the signal transduction, although neither target molecules nor molecular mechanisms are at present known. In this study we found that application of a MF to Jurkat cells resulted in significant increase of inositol 1,4,5-trisphosphate (IP3) levels. Chelation of intracellular calcium ions by BAPTA/AM, did not block the increase of IP3 induced by MF. This result implied that MF-induced Ca2+ oscillations were not due to direct stimulation of the Ca(2+)-dependent phospholipase C-gamma 1 (PLC-gamma 1). PMID- 7867789 TI - Annexin V perturbs or stabilises phospholipid membranes in a calcium-dependent manner. AB - The potency of annexin V to transport Ca2+ ions across phospholipid membranes was investigated, using large unilamellar phospholipid vesicles loaded with the Ca2+ indicator fura-2. It was demonstrated that annexin V leaves the vesicle membranes intact when added in the presence of 1 mM Ca2+. However, if the vesicles were first incubated with annexin V in the absence of Ca2+, subsequent addition of Ca2+ produced a fluorescence signal due to binding of Ca2+ to fura-2. Centrifugation of the vesicle suspension immediately thereafter showed that this signal originated from the supernatant and not from the sedimented vesicles. Our results show that annexin V causes loss of vesicle integrity in the absence of Ca2+, and leakage of trapped fura-2, rather than inward Ca2+ transport. Bovine serum albumin or Ca2+ concentrations higher than 2.5 mM also caused such fura-2 leakage. Apparently, calcium-dependent binding of annexin V to the membrane prevents aspecific membrane damage caused by this protein. PMID- 7867790 TI - Nucleotide binding by the synapse associated protein SAP90. AB - The rat synapse associated protein SAP90 is a member of a superfamily of potential guanylate kinases localized at cell-cell contact sites. This superfamily includes the synapse associated protein SAP97, a close relative of SAP90, the Drosophila tumor suppressor gene product dlg-Ap, the mammalian zonula occludens proteins ZO-1 and ZO-2 and the erythrocyte protein p55. Here we show that SAP90 specifically binds GMP in the micromolar range while binding to ATP, GDP and ADP is at a much lower affinity (10-25 mM), whether or not binding is detected for other guanine and adenine nucleotides. No guanylate kinase activity of SAP90 was detected under our experimental conditions. The importance of the GMP binding capacity per se and an evolutionary role for conserving of the guanylate kinase domain in this superfamily are discussed. PMID- 7867791 TI - 'Brain-type' N-glycosylation of asialo-transferrin from human cerebrospinal fluid. AB - Asialo-transferrin from human cerebrospinal fluid was purified to homogeneity. Investigation of the structural characteristics of its oligosaccharides support our hypothesis of 'brain-type' glycosylation of intrathecally synthesized cerebrospinal fluid proteins. For carbohydrate structural analysis, high-pH anion exchange chromatography, methylation analysis, liquid secondary ion- and matrix assisted laser desorption/ ionization mass spectrometry of the permethylated derivatives were used. The major structure turned out to be a complex-type agalactodiantennary oligosaccharide with bisecting N-acetylglucosamine and proximal fucose. Analysis of a second transferrin preparation containing both asialo- and sialo-transferrin revealed another major glycan species derived from the sialylated transferrin variant which is galactosylated and lacks bisecting N acetylglucosamine and fucose. PMID- 7867792 TI - Purification and characterization of the N-terminal domain of galectin-4 from rat small intestine. AB - Using affinity chromatography on lactose-agarose, five beta-galactoside binding lectins of 14 to 20 kDa were detected in the rat small intestinal mucosa. The prominant proteins of 17 and 19 kDa were purified to homogeneity by 2D electrophoresis. Direct N-terminal sequencing of the 17 kDa protein and intrachain sequencing of the 19 kDa protein produced sequences which are part of the N-terminal domain of the L-36/galectin-4. A rabbit polyclonal antibody was raised against the 19 kDa lectin, which specifically recognized the 17 and 19 kDa lectins and detected a related 36 kDa protein in human undifferentiated HT29 cells. PMID- 7867793 TI - The proteasome from Thermoplasma acidophilum is neither a cysteine nor a serine protease. AB - The 20 S proteasome, found in eukaryotes and in the archaebacterium Thermoplasma acidophilum, forms the proteolytic core of the 26 S proteasome which is the central protease of the non-lysosomal protein degradation pathway. Inhibitor studies have indicated that the 20 S proteasome may be an unusual type of cysteine or serine protease and a recent study of the Thermoplasma beta subunit has indicated that it carries the proteolytic activity. We have attempted to obtain information on the nature of the active site by mutating the only cysteine, both histidines and two completely conserved aspartates in the archaebacterial complex as well as all serines of the beta subunit, without decreasing the catalytic activity of the enzyme to any significant extent. Indeed, mutation of the conserved aspartate in the beta subunit increased the activity of the proteasome threefold. We conclude that the proteasome is not a cysteine or serine protease. PMID- 7867794 TI - Substrate specificity of rat liver mitochondrial carnitine palmitoyl transferase I: evidence against alpha-oxidation of phytanic acid in rat liver mitochondria. AB - The two branched chain fatty acids pristanic acid (2,6,10,14 tetramethylpentadecanoic acid) and phytanic acid (3,7,11,15 tetramethylhexadecanoic acid) were converted to co-enzyme A thioesters by rat liver mitochondrial outer membranes. However, these branched chain fatty acids could not be converted to pristanoyl and phytanoyl carnitines, respectively, by mitochondrial outer membranes. As expected, the unbranched long chain fatty acids, stearic acid and palmitic acid, were rapidly converted to stearoyl and palmitoyl carnitines, respectively, by mitochondrial outer membranes. These observations indicate that the branched chain fatty acids could not be transported into mitochondria. The data presented strongly suggest that in rat liver, alpha-oxidation of phytanic acid occurs in organelles other than mitochondria. PMID- 7867795 TI - Secondary structure and folding topology of the DNA binding domain of interferon regulatory factor 2, as revealed by NMR spectroscopy. AB - The secondary structure elements of the DNA-binding domain of mouse interferon regulatory factor 2 [IRF-2(113)] were determined by heteronuclear multidimensional NMR spectroscopy. The sequential NOE connectivities, amide proton exchange rates, and 3JHN alpha coupling constants indicated the presence of three alpha-helical regions and four short beta-strands connected through relatively long loops. The long range NOEs indicated the four strands form an antiparallel beta-sheet and the three alpha-helices form a bundle on the sheet. The arrangement of the secondary structure elements and the overall folding topology resemble those of the DNA binding domains of bacterial activator CAP, heat shock transcription factors, and fork-head proteins, although there is no sequence homology among them. PMID- 7867796 TI - The monoclonal antibody specific for the 4-hydroxy-2-nonenal histidine adduct. AB - Monoclonal antibodies directed against proteins modified with the major membrane lipid peroxidation product, 4-hydroxy-2-nonenal, have been established and characterized. The monoclonal antibodies specific for HNE-modified proteins were raised by immunizing mice with a HNE-keyhole limpet hemocyanin conjugate. The resulting five monoclonal antibodies (mAbs HNEJ-1-5) recognized HNE-modified bovine serum albumin (BSA), but not native BSA in Western blot studies. Of the five mAbs, HNEJ-2 exhibited the highest affinity for HNE-modified proteins and a much higher affinity for the HNE-histidine adduct than the HNE-lysine or HNE cysteine adducts. mAb HNEJ-2 did not cross-react with proteins that had been treated with other aldehydes, such as 1-hexenal, 2-hexenal, 4-hydroxy-2-hexenal, 2-nonenal, formaldehyde, or glutaraldehyde. These results suggest that the major epitope recognized by mAb HNEJ-2 is the Michael addition-type HNE-histidine adduct. PMID- 7867797 TI - The use of mass spectrometry to examine the formation and hydrolysis of the phosphorylated form of phosphoglycerate mutase. AB - Electrospray mass spectrometry has been used to study the formation and hydrolysis of the phosphorylated forms of two phosphoglycerate mutases. The half life of the enzyme from Saccharomyces cerevisiae was 35 min at 20 degrees C in 10 mM ammonium bicarbonate, pH 8.0. Addition of 1 mM 2-phosphoglycollate reduced this value by at least 100-fold. The phosphorylated form of the enzyme from Schizosaccharomyces pombe was much less stable with a half-life of less than 1 min. The results are discussed in terms of the kinetic properties of the enzymes. Mass spectrometry would appear to be a powerful method to study the formation and breakdown of phosphorylated proteins, processes which are of widespread significance in regulatory mechanisms. PMID- 7867798 TI - Chaperonin releases the substrate protein in a form with tendency to aggregate and ability to rebind to chaperonin. AB - To know whether the protein released from chaperonin GroEL/ES is in a form committed to the native state or still an aggregatable non-native one, two experiments were carried out. Dilution of the [GroEL-substrate protein] binary complex prior to ATP addition significantly improved the yield of folding, suggesting that the released protein has a tendency to aggregate. When N ethylmaleimide treated GroEL, which can form the binary complex but not release the bound protein, was added to the binary complex prior to ATP addition, productive folding was severely inhibited, indicating that the protein released from GroEL/ES can bind to N-ethylmaleimide treated chaperonin. These data favor the 'reservoir' or 'reversion' model, in which GroEL/ES acts as a buffer of folding intermediate or mediates reversion of a misfolded protein to a less folded primitive form, rather than the 'marsupium' model in which folding of the substrate protein proceeds in chaperonin. PMID- 7867799 TI - Melanin-concentrating hormone binding to mouse melanoma cells in vitro. AB - An analogue of human melanin-concentrating hormone (MCH) suitable for radioiodination was designed in which Tyr13 was replaced by Phe and Val19 by Tyr. The resulting monoiodinated [125I] [Phe13,Tyr19]-MCH radioligand was biologically active and led to the discovery of high-affinity binding sites on mouse B16-F1, G4F and G4F-7 melanoma cells. Saturation binding analysis with G4F-7 cells revealed 1090 MCH receptors per cell and a KD of 1.18 x 10(-10) mol/l. Receptors for MCH were also found on rat PC12 phaeochromocytoma cells, human RE melanoma cells and COS-7 cells. Competition binding analyses with other peptides such as alpha-MSH, NPY and PACAP demonstrated that MCH receptor binding is specific. rANF(1-28) was found to be a weak competitor of MCH, indicating topological similarities between MCH and rANF(1-28) when interacting with MCH receptors. PMID- 7867800 TI - Molecular diagnosis of transthyretin Met30 mutation in an Italian family with familial amyloidotic polyneuropathy. AB - We report the molecular analysis of the transthyretin gene in a large Italian pedigree with familial amyloidotic polyneuropathy and demonstrate the presence of a Met30 mutation. The usefulness of the genetic analysis in the identification of presymptomatic persons and the diagnosis of individuals with partial symptoms is discussed. PMID- 7867801 TI - The 3' untranslated region of bovine preprolactin contains a transferable non poly(A) mRNA sequence that prolongs translation. AB - Preprolactin transcripts, synthesized in vitro, were actively translated for a prolonged period when injected into Xenopus oocytes. As a result, prolactin continued to be secreted into the media for up to 6 days after injection of the transcript. To investigate the role of the preprolactin 3' untranslated sequence in stabilizing transcripts, it was fused to coding regions derived from signal recognition particle receptor alpha-subunit or preproinsulin receptor. The translational half-life of the chimeric RNA was increased for both coding regions, suggesting that a sequence within the preprolactin 3' untranslated region that prolongs translation is transferable. Deletion mutagenesis of this untranslated region demonstrated that a sequence of 98 nucleotides immediately following the prolactin stop codon was sufficient to prolong translation of RNAs injected into Xenopus oocytes. PMID- 7867802 TI - The molecular basis for genetic polymorphism of human deoxyribonuclease I: identification of the nucleotide substitution that generates the fourth allele. AB - In addition to the three alleles commonly responsible for the protein polymorphism of human deoxyribonuclease I, a mutation encoded by a fourth allele, DNASE1*4, was detected by isoelectric focusing. All 8 exons covering the entire open reading frame of the human DNase I gene were amplified by the polymerase chain reaction and subjected to direct sequencing. Only one nucleotide substitution, a C-to-G transition (CAG-->GAG), in the codon for amino acid 9 of the mature enzyme was found. This substitution resulted in the replacement of Gln with Glu (Q9E). PMID- 7867804 TI - Internal actin filament dynamics in the presence of vinculin: a dynamic light scattering study. AB - Analyses of dynamic light scattering data by stretched exponential fit show that vinculin has a negligible influence on internal actin filament dynamics and actin bending stiffness which contrasts with our previous observations with talin, another actin and vinculin-binding protein from focal adhesions. The results here agree with kinetic and rheologic measurements. PMID- 7867803 TI - A second nitrogen permease regulator in Saccharomyces cerevisiae. AB - We describe a Saccharomyces cerevisiae mutant affected in its urea and proline transport capacities, and a gene coding for a protein complementing this mutation. This protein is not membrane-embedded and contains two PEST sequences, often found in regulatory factors. The mRNA is not down-regulated under nitrogen catabolite repression, and is induced by urea and proline. In the mutant, the PUT4 mRNA encoding the proline permease is not affected, whereas the DUR3 mRNA, involved in urea active transport, is strongly increased. Our data suggest that this protein is a post-transcriptional regulator of nitrogen permeases. PMID- 7867805 TI - Involvement of Mg2+ in terminating Ca2+ release in cultured rat skeletal muscle. AB - Combined patch-clamp and fura-2 measurements were performed to investigate the mechanism that terminates Ca2+ release in rat skeletal myoballs. When cells were intracellularly perfused with solution containing 1 mM free Mg2+, the caffeine (10 mM)-induced Ca2+ transient was abruptly terminated by membrane repolarization (-70 mV). With low intracellular Mg2+ (e.g. 50 microM) perfusion, however, repolarization failed to terminate the caffeine transient. The results show that intracellular Mg2+ is necessary for repolarization-induced closing of the Ca2+ release channel. PMID- 7867807 TI - Purification and characterization of the Rieske iron-sulfur protein from the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius. AB - The previously detected Rieske iron-sulfur protein from the membranes of the thermoacidophile Sulfolobus acidocaldarius [Anemuller, S., et al. (1993) FEBS Lett. 318, 61-64] was purified to electrophoretic homogeneity and the N-terminal amino acids determined. The apparent molecular weight was estimated to be 32 kDa. The reduced protein displays a rhombic EPR spectrum with gxyz = 1.768, 1.895, 2.035. The average g-value of 1.902 is typical for nitrogen ligand-containing clusters. EPR spin quantification and the iron content indicate the presence of one [2Fe-2S] cluster. The purified protein displays ubiquinol cytochrome c reductase activity. The pH optimum of this reaction is temperature dependent and was determined to be pH 7 at 56 degrees C. The results presented in this study clearly prove that the Sulfolobus Rieske protein belongs to the family of the true Rieske iron-sulfur proteins. PMID- 7867806 TI - Shape oscillations: a fundamental response of human neutrophils stimulated by chemotactic peptides? AB - Neutrophils undergo periodic cytoskeletal rearrangements that lead to cycles of shape change, ultimately resulting in cell translocation. Repeated stimulation of resting neutrophils with subsaturating chemoattractant doses induced transient sinusoidal oscillations in neutrophil filamentous actin content at the second and subsequent stimulations. Oscillation frequencies increased with increasing concentration of the first stimulus. In contrast, neutrophils pretreated with the phosphatidylinositol 3-kinase inhibitor (17-hydroxy)wortmannin displayed shape oscillations with the first stimulation, and the frequencies were independent of agonist type and dose. We demonstrate that oscillations in filamentous actin, which may be critical for neutrophil motility, can be induced in untreated cells by natural peptide chemoattractants. PMID- 7867808 TI - Purification, crystallisation and preliminary X-ray analysis of the vanadium dependent haloperoxidase from Corallina officinalis. AB - The vanadium-dependent haloperoxidase from the seaweed Corallina officinalis has been purified to homogeneity and crystallised. The protein is reported to be a hexamer of 12 x 64,000 Da, contains no haem, and is dependent on vanadium for activity. The crystals are grown from polyethylene glycol (PEG) 6,000 and 0.4 M potassium chloride. They are stable and diffract to better than 2 A resolution. They are of a cubic space group I23 (or 12(1)3) with cell dimensions a = b = c = 310 A. PMID- 7867809 TI - Electrogenic Na+ transport by Enterococcus hirae Na(+)-ATPase. AB - Energy-dependent generation of a membrane potential (delta psi) (-45 mV, interior negative) was observed in the F0F1, H(+)-ATPase-defective mutant of Enterococcus hirae. The generation of delta psi was found at high pH (but not at low pH), for which intracellular Na+ was required but not extracellular K+. The delta psi generating activity was induced in cells cultured in media containing high concentrations of Na+, and was not observed in the Na(+)-ATPase mutants. These results suggest that E. hirae Na(+)-ATPase is responsible for the electrogenic sodium pump. PMID- 7867810 TI - UCN-01, an anti-tumor drug, is a selective inhibitor of the conventional PKC subfamily. AB - A selective PKC inhibitor, UCN-01, was shown to exhibit anti-tumor activity in vitro and in vivo. We investigated UCN-01 with respect to isozyme-specific PKC inhibition using purified recombinant or rabbit brain PKC isozymes, cPKC alpha, beta and gamma, nPKC delta, epsilon and eta, and a PKC zeta. Of the PKC isozymes examined, cPKC alpha was inhibited by UCN-01 most effectively (Ki = 0.44 nM), suggesting cPKC alpha is the prime candidate for the physiological target of UCN 01. The Ki values of UCN-01 estimated from Dixon plots for cPKC isozymes are approximately 1 nM, whereas the Ki values for nPKC isozymes are about 20 nM. Moreover, the Ki value for aPKC zeta is 3.8 microM. Thus, UCN-01 discriminates between PKC subfamilies. In addition, the inhibitory effects of staurosporine, H7, and calphostin C on aPKC zeta were examined and compared with those for cPKC alpha. PMID- 7867811 TI - Regulation of alpha 1-antichymotrypsin synthesis in cells of epithelial origin. AB - Oncostatin M, interleukin-1 and the glucocorticoid analog, dexamethasone, have been identified as potent stimulators of alpha 1-antichymotrypsin production in various cells of epithelial origin. Although being able to act individually, these factors exerted a dramatic increase in alpha 1-antichymotrypsin synthesis when administrated in combination. Their stimulatory effect was independent of the levels of constitutive synthesis of this inhibitor, which was already high in lung- and breast- and low in skin-derived epithelial cells. Since alpha 1 antichymotrypsin controls chymotrypsin-like proteinases which are released during inflammation, these data support the concept that local synthesis of this inhibitor may be important in reducing tissue damage associated with this process. PMID- 7867812 TI - Changes in redox affect the activity of erythropoietin RNA binding protein. AB - We have previously identified a cytosolic protein, erythropoietin RNA binding protein (ERBP), which is up-regulated in certain tissues in response to hypoxia. To further characterize the interaction of ERBP and erythropoietin (EPO) mRNA, we have examined the role of reduction-oxidation in the EPO mRNA binding mechanism of ERBP isolated from human hepatoma cells (Hep3B). Reducing agents dithiothreitol (DTT) and 2-mercaptoethanol (2-ME) increased ERBP binding activity in a concentration-dependent manner, whereas the oxidizing agent, diamide, abolished ERBP binding activity. In addition, treatment of Hep3B cell lysates with the irreversible sulfhydryl alkylating agent N-ethylmaleimide resulted in inhibition of the EPO mRNA-ERBP complex. Taken together, these findings suggest that sulfhydryl groups may play a role in vivo in the regulation of EPO production through the modulation of ERBP binding activity. PMID- 7867813 TI - Saps and tears. PMID- 7867814 TI - Stickler syndrome: correlation between vitreoretinal phenotypes and linkage to COL 2A1. AB - Stickler syndrome is an autosomal dominantly inherited condition characterised by ocular, articular, facial, auditory and oral features. There is locus heterogeneity with about two thirds of families showing linkage to the gene encoding type II procollagen (COL 2A1). Clinical overlap with Marshall's, Wagner's and other syndromes has caused considerable confusion but the importance of the congenital vitreous anomaly, as first described by Scott, has not previously been emphasised. This study examines the linkage of two vitreo-retinal phenotype subgroups of Stickler syndrome to COL 2A1. A total of 97 affected patients from 24 pedigrees were examined. This is the largest published series of Stickler syndrome patients to date and all have undergone full clinical and ophthalmological examination by a single investigator. A clinical classification is proposed based on vitreoretinal phenotype. All patients demonstrating the congenital vitreous anomaly have been designated Stickler syndrome type 1 and those without the congenital vitreous anomaly as Stickler syndrome type 2 patients. There were 69 affected patients from 20 unrelated type 1 pedigrees and 28 affected patients from 4 unrelated type 2 pedigrees. Using two markers at the COL 2A1 locus, Stickler syndrome type 1 pedigrees showed complete linkage to COL 2A1 with a maximum lod score of 12.33 at zero recombination. Linkage to COL 2A1 was excluded in the two type 2 pedigrees that were informative. From these data it appears that this clinical classification is a useful first step in resolving the genetic heterogeneity in this condition. PMID- 7867815 TI - Traumatic retinal angiopathy and seat belts: pathogenesis of whiplash injury. AB - Three cases of traumatic retinal angiopathy associated with whiplash injury are presented. The pathogenesis of the fundal appearances is discussed. Local microcirculatory disturbances are postulated as the cause of the retinopathy as opposed to the systemic disturbance associated with Purtscher's retinopathy. This condition may be underdiagnosed as there may be few abnormal signs on funduscopy. Fluorescein angiography may be very helpful. The incidence may be increasing as a result of legislation concerning the wearing of seat belts, and the condition has medico-legal significance. Increasing awareness may increase diagnosis. PMID- 7867816 TI - The presentation of children with amblyopia. AB - This study reports the presentation of 961 children who underwent amblyopia treatment at seven orthoptic centres in the United Kingdom. We confirmed previous authors' findings of a small but significant increased incidence of left-sided compared with right-sided amblyopia overall. For pure anisometropic amblyopia this difference was very marked and a possible pathophysiological mechanism is proposed. The mean age of presentation for anismetropic, strabismic and mixed amblyopia was 5.6, 3.3 and 4.4 years, respectively. Neither sex nor race affected the age of presentation. Despite their older age, children with pure anisometropic amblyopia had the best initial visual acuity, with 25% of anisometropes having an initial visual acuity of less than 6/18 compared with 39% of strabismics and 50% of mixed amblyopes. The ages and initial acuities of the strabismic patients in this series are at least as favourable as those of patients reported from outside the UK. There were variations in the age and proportion of patients presenting with anisometropic amblyopia at the different centres, suggesting a failure in the referral of anisometropic amblyopia of importance in interpreting epidemiological studies. PMID- 7867817 TI - Factors affecting the outcome of children treated for amblyopia. AB - The outcome of treatment for amblyopia and the factors that affect this are not well understood. A major reason for this has been the exclusion from previous large studies of a sometimes unknown number of patients because of failure to comply with treatment. This paper analyses the outcome of amblyopia treatment in a retrospective review of the orthoptic records of a cohort of 961 children treated for amblyopia at seven centres who first attended in 1983. The final visual acuity was recorded by Snellen or matching methods in 894 children (93%). Of these, 48% achieved 6/9 or better, 35% less than 6/9 but better than or equal to 6/18, and 17% achieved less than 6/18. The outcome was best for pure anisometropic amblyopia, intermediate for pure strabismic amblyopia and least good for mixed strabismic and anisometropic amblyopia with a final visual acuity of 6/10.2, 6/12.8 and 6/14.8 respectively. While the age at start of treatment did not correlate with final visual acuity both poor initial visual acuity and poor compliance were associated with poor outcome. The main factor affecting the outcome of amblyopia treatment is the initial visual acuity. Comparison with the literature suggests that the results of treatment in this country may be falling far short of what would be possible in ideal circumstances with unlimited resources. PMID- 7867818 TI - The outcome of strabismus surgery in childhood exotropia. AB - The results of squint surgery in 42 children with primary, non-paralytic, childhood exotropia are analysed. A 'favourable outcome', defined as a final alignment for near and distance within +/- 10 dioptres of straight, or within +/- 20 dioptres of straight with evidence of binocular single vision, was achieved in 39 (93%) children. The factors affecting the final outcome are discussed, including age of onset, age at the time of surgery, preoperative and post operative amblyopia, refractive error, anisometropia, the surgical procedures used, and postoperative ocular alignment. PMID- 7867819 TI - Flash and pattern visual evoked potentials in the diagnosis and monitoring of dysthyroid optic neuropathy. AB - Flash and pattern visual evoked potentials were recorded in 8 patients (13 eyes) with dysthyroid optic neuropathy (DON), diagnosed using the American Thyroid Association classification. All were treated with systemic steroids, but 4 patients (6 eyes) also required orbital decompression. Flash VEP (P2) and pattern VEP (P100) were recorded prior to and 2 weeks after commencing steroid treatment or decompression. Fifteen patients with Graves orbitopathy but without DON, and 20 healthy subjects, acted as controls. Before treatment visual acuity was reduced in 10 eyes and visual fields were abnormal in 5, but the VEP was abnormal in all 13, with the group mean amplitude of P2 and P100 significantly less than controls, and the group mean P100 latency significantly greater than controls. After treatment with high-dose steroids or surgical decompression there were significant improvements in the group mean amplitude of P2 and P100, and significant reductions in P2 and P100 latency; however, individually, improvements in amplitude were more significant than improvements in latency. We conclude that the VEP to flash and pattern stimuli provides a useful diagnostic and monitoring tool in patients with DON, combining objectivity with quantitative analysis. PMID- 7867820 TI - Neuro-ophthalmic findings in botulism type B. AB - In June 1989, the largest recorded outbreak of food-borne botulism occurred in the United Kingdom. Twenty-seven patients were affected during the outbreak with type B botulism. A case note review of 14 patients admitted with this condition was performed and the neuro-ophthalmic findings are presented. Patients with severe disease presented with a combination of ocular and bulbar symptoms; in mild cases dysphagia was noted first and visual disturbance followed within 24 hours. Clustering of cases and bilaterality of cranial nerve signs aided in the diagnosis. Accommodative paresis and sixth cranial nerve palsy were frequent early signs. When there was respiratory paralysis and ventilatory failure, it occurred within 12 hours of the onset of a third cranial nerve palsy. PMID- 7867821 TI - In vivo documentation of cellular reactions on lens surfaces for assessing the biocompatibility of different intraocular implants. AB - This prospective study was undertaken to assess the biocompatibility of different intraocular implants and to determine factors influencing cellular reactions on intraocular lenses (IOLs). Cellular reactions seen on the surface of 653 IOLs have been documented by specular microscopy. Various types of IOLs were used with different surgical procedures in humans. The 11 lens types used fall into five groups of materials: polymethylmethacrylate (PMMA), heparin surface-modified PMMA, surface-modified PMMA, poly Hema and silicone. Factors influencing the cellular reaction on intraocular implants were elaborated on in this study. Besides the foreign-body reaction itself, cellular reactions were influenced by an increased inflammatory disposition, surgical trauma, peri-operative treatment, implant positioning and lens style. A significant correlation was found between the development of posterior synechiae and the existence of giant cells on the anterior lens surface. The incidence of cellular reactions on IOLs revealed significant differences specific to lens and material. Hydrophilic surfaces show cellular reactions in a lower percentage of cases compared with hydrophobic surfaces. An accurate and individual selection of lens material and style is mandatory to guarantee optimal after surgery. PMID- 7867822 TI - Reproducibility study of posterior subcapsular opacities on the NEI retroillumination image analysis system. AB - We developed a semi-automated retroillumination image analysis system which combines speed, ease of operation and interactive analysis. The system measures cataract area and integral of cataract density (ID). For system reproducibility evaluation, 20 eyes with posterior subcapsular opacities were captured twice by two photographers. Variability was estimated under a random effects analysis of variance model. Measurement errors for area and for ID were each small contributors to total variability (the sum of variability between study eyes plus measurement error), being 0.4% and 0.1% respectively. The largest contributor to area measurement error was image analysis variability (97%). For ID measurement error, the variability in images (44%) and in image analysis (46%) were major contributors. The reproducibility is comparable to previously described retroillumination analysis systems. This easy to use system may therefore be useful in clinical research studies including possible clinical trials of anti cataract drugs. PMID- 7867823 TI - Ocular biometry in pre-term infants without retinopathy of prematurity. AB - Serial ocular A-scan ultrasound biometry was performed on 100 pre-term infants (less than 32 weeks gestation and/or less than 1500 g) who did not show features of retinopathy of prematurity (ROP) during a screening programme. Axial length increased from 15.38 +/- 0.25 mm at 33 weeks post-menstrual age to 16.88 +/- 0.59 mm at 41 weeks (rate of growth 0.18 mm/week, r = 0.99). The rate of growth appeared to slow down after 40 weeks (term) to 3 months post-term. Male infants had longer eyes and a greater rate of growth than female infants. Axial length (AL) was significantly correlated with birth weight, biparietal and occipito frontal diameter in the weeks after birth. Between weeks 33 and 41, the anterior chamber depth (ACD) increased from 1.92 +/- 0.13 mm to 2.43 +/- 0.18 mm, and lens thickness (LT) increased from 3.82 +/- 0.33 mm to 3.90 +/- 0.13 mm. The largest percentage growth between weeks 33 and 41 occurred in ACD (22%), followed by vitreal length (10%), AL (9%) and LT (2%). These data will help in future studies on the role which ROP plays in the development of ocular growth. PMID- 7867824 TI - Visual experience during cataract surgery. AB - Fifty-six sequential patients undergoing cataract surgery using local anaesthesia were invited to complete a questionnaire recording their visual experiences during the surgery. A majority had peribulbar anaesthesia; none had pre- or per operative sedation. Fifty-four of the patients could see with their eye during the surgery. Two of these patients could perceive only a bright light; the remainder recorded colours (80%), followed by movements (68%), flashes (66%), abstract colour images (55%) and perception of objects (20%). In two-thirds the brightness of the light changed during the course of the operation (most commonly getting brighter) and in one-third the colours perceived changed during the operation. Pictures were drawn by 22 of the patients of their experience during the surgery. PMID- 7867825 TI - Effect of betaxolol on the retinal circulation in eyes with ocular hypertension: a pilot study. AB - This study investigated the effect of betaxolol, a beta 1 selective blocker, on the retinal circulation in 10 patients with ocular hypertension. In a masked randomised fashion, one eye of each subject received betaxolol and the fellow eye received placebo (hypromellose). Retinal blood flow (RBF) was determined in a major temporal vein of each eye just prior to instillation of drops and 2 h later, using laser Doppler velocimetry and monochromatic fundus photography. There was an increase of 15.0% in RBF (p = 0.03) in the betaxolol-treated eyes. No significant change was observed in the placebo-treated eyes. Intraocular pressure was reduced by 27.7% in the treated eyes, resulting in an increase of 16.9% in perfusion pressure (p = 0.02) compared with an 8.4% increase in placebo treated eyes (p = 0.15). This study demonstrated that betaxolol increases RBF in eyes with ocular hypertension; this increase is probably related to the increase in perfusion pressure. PMID- 7867826 TI - Preliminary results with a new hydrogel intraocular lens. AB - The merits of hydrogel as an intraocular lens material are that it is soft, foldable, hydrophilic, autoclavable and more biocompatible than polymethylmethacrylate (PMMA). Twenty eyes were implanted with a new hydrogel design after phacoemulsification. Fifty per cent achieved a corrected acuity of 6/5 and all achieved 6/9 with correction. Results confirmed an excellent biocompatibility of the material but two cases of asymptomatic decentration indicated the occasional instability within the capsular sac. For best results the hydrogel requires an intact capsulorrhexis with a diameter between 4.5 and 5.0 mm. PMID- 7867827 TI - In situ degradation of 11/0 polyester (mersilene) suture material following cataract surgery. AB - Two hundred and ten patients (231 eyes) had their cataract sections closed with 11/0 polyester suture material over a 4 year period. Their case sheets were assessed to determine the number of eyes from which sutures had been removed prior to discharge, and for what reasons these sutures were removed. Ninety-seven patients (107 eyes) with sutures left in situ were further assessed to determine whether they were suffering from any suture-related symptoms and examined to determine the degree of clinical biodegradation experienced by the sutures. Six of these sutures were removed for electron microscopic examination. Of the 231 eyes initially included, 61 sutures (26.4%) had been removed prior to discharge. None of the 107 sutures examined showed evidence of clinical biodegradation; this was confirmed by electron microscopic analysis which showed only minimal erosion of sutures even after 48 months in situ. PMID- 7867828 TI - Decentration of the posterior chamber lens implant: a comparison of capsulorhexis with endocapsular surgery. AB - The optical effect of posterior chamber lens decentration is a well-recognised complication of cataract surgery causing significant symptoms even with the larger-diameter implant optics available. In this paper we present the results of a study of implant decentration occurring with extracapsular surgery, in which we compared a group of patients with one tear in the anterior capsule with a second group with two tears in the anterior capsule. Our findings show that lens decentration is greater in those patients with two tears of the anterior capsule, and this difference is statistically significant. PMID- 7867829 TI - Detection of varicella-zoster virus DNA in ocular samples from patients with uveitis but no cutaneous eruption. AB - Herpes zoster ophthalmicus is a well-recognised cause of intraocular inflammation, which may become recurrent or chronic after the acute phase has elapsed. Although it commonly presents with the typical rash, cases of ocular zoster with no cutaneous eruption have been well documented. We present two patients with unilateral anterior uveitis complicated by cataract, in whom molecular techniques based on the polymerase chain reaction detected varicella zoster virus DNA in intraocular material obtained during cataract surgery. Neither patient gave a history of cutaneous eruption. PMID- 7867830 TI - Comparison of topical and oral acyclovir in early herpes zoster ophthalmicus. AB - Poor systemic absorption has limited the efficacy of early oral acyclovir in herpes zoster ophthalmicus (HZO). Aqueous humour levels are substantially higher if the drug is administered topically to the eye. A multicentre open randomised study was performed to compare the ocular prophylactic effects of topical and oral acyclovir. Fifty-seven patients with HZO within 72 hours of the onset of rash received either topical acyclovir ointment or 800 mg oral acyclovir, both 5 times daily for 7 days, and were followed for 12 months. Patients receiving ointment were significantly more likely to have ocular complications (p < 0.02) and anterior uveitis was significantly more frequent (p < 0.01) and severe (p < 0.01). Corneal hypoaesthesia was significantly more frequently (p < 0.05) and severe (p < 0.02) at 1 month. From 2 weeks patients receiving ointment were more likely to have pain and at all times their pain was more severe, but these differences were not statistically significant. In spite of its apparently better penetration topical acyclovir appears to have no prophylactic value in the management of early HZO. PMID- 7867831 TI - Keratitis due to the fungus Acremonium (Cephalosporium) PMID- 7867832 TI - Acute kerato-uveitis associated with topical self-administration of the sap of the Petty Spurge (Euphorbia peplus) PMID- 7867833 TI - Euphorbia lathyris latex keratoconjunctivitis. PMID- 7867834 TI - A severe, antineutrophil cytoplasmic antibody associated, anterior segment vasculitis. PMID- 7867835 TI - Toxic retinopathy secondary to repeat intravitreal amikacin and vancomycin. PMID- 7867836 TI - Congenital tarsal kink: a rare cause of neonatal corneal ulcers. PMID- 7867837 TI - Microsporidial keratoconjunctivitis treated successfully with a short course of fumagillin. PMID- 7867838 TI - The merocel nasal tampon: its use in lacrimal and oculoplastic surgery. PMID- 7867839 TI - Vitreous haemorrhage after hyberbaric oxygen therapy. PMID- 7867840 TI - Epiretinal membranes presenting in two young adults with evidence of persistent primary vitreous. PMID- 7867841 TI - Betaxolol-associated anterior uveitis. PMID- 7867842 TI - Retinal changes in scurvy. PMID- 7867843 TI - Ocular injury resulting from bungee-cord jumping. PMID- 7867844 TI - Retinal vasculitis and uveitis in IgA nephritis. PMID- 7867845 TI - Bamboo orbital foreign body mimicking air on computed tomography. PMID- 7867846 TI - Failure of topical bupivacaine to relieve pain after vitreoretinal surgery. PMID- 7867847 TI - Detection of an orbital foreign body by a skull radiograph prior to magnetic resonance imaging. PMID- 7867848 TI - Hermann Ludwig Ferdinand von Helmholtz (1821-1894) PMID- 7867849 TI - Respiratory function in patients changed from timolol. PMID- 7867850 TI - Outpatient management of small traumatic hyphaemas. PMID- 7867851 TI - Treatment of Acanthamoeba keratitis. PMID- 7867852 TI - [Proceedings of the 67th Congress of the Japan Endocrine Society. Hiroshima, Japan. November 16-7, 1994. Abstracts]. PMID- 7867853 TI - Canada's healthcare system: what now, eh? PMID- 7867854 TI - Trisomy 13 karyotype within 24 hours from a cord blood specimen. PMID- 7867855 TI - To Russia and back again: the tale of two medical missions to Moscow. PMID- 7867856 TI - Occupational infection with hepatitis C virus in the healthcare setting. AB - Our understanding of the types of hepatitis described previously as non-A, non-B hepatitis has been revolutionized by the discovery of two new viruses, hepatitis C virus (HCV) and hepatitis E virus. HCV is transmitted parenterally, and poses a potential occupational hazard to health care workers, including dental staff. No vaccine is currently available, and it is important that an assessment of infection risk is made available to clinicians. PMID- 7867857 TI - Erosion in children: an increasing clinical problem? AB - Tooth wear is becoming more common in both adults and children. The triad of attrition, abrasion and erosion has been known for many years, but the contribution of erosion (irreversible loss of dental hard tissue due to a chemical process not involving bacteria, or the loss of tooth surface not directly associated with mechanical or traumatic factors or caries) to excessive loss of tooth tissue is now being emphasized. The authors of this paper examine the problem and suggest ways of overcoming it. PMID- 7867858 TI - An update on conventional fixed bridges. Part 1: Patient assessment and selection. AB - Over the past decade there have been many developments in the field of adhesive bridgework, a conservative treatment option for the patient with intact and unrestored abutment teeth. However, many situations still exist where resin bond retained bridges are unsuitable and more conventional techniques are called for. Although adhesive bridges are potentially less damaging to tooth structure, conventional bridgework has greater implications in terms of damage to abutment teeth and surrounding tissues. It is important to execute a carefully devised treatment plan skillfully if problems are to be avoided. This paper, the first in a series of 5 articles offering biologically based, practical guidelines to the dental surgeon, discusses how patients should be selected for these procedures. PMID- 7867859 TI - The brown bear in Europe: its plight and dental needs. AB - The brown bear is one of the most persecuted animals in the world. In Greece, Turkey, Pakistan and India they are used as dancing spectacles by gypsies. The mother is killed so that the cubs can be captured at a very early age and subjected to training that involves extreme cruelty: starvation, beatings and red hot metal plates, as well as rings and chains through their noses and lips, are used to make the animals stand on their hind feet and mimic a dance routine so that their handlers can collect money in the streets. The author describes the treatment of the first bears to benefit from the facilities at the new Bear Protection Centre set up by Arcturos. PMID- 7867860 TI - Orthodontic treatment in adults with periodontally involved labial segments. AB - During the last two decades notable advances have been made in the management of periodontal diseases. A better understanding of the basic biological principles of periodontal wound healing has provided a sound foundation for placing greater emphasis on conservative treatment regimes, including non-surgical treatments, less radical surgical techniques and the use of guided regenerative procedures to restore connective tissue attachment lost during disease progression. The consequence of these advances is that, even in cases of severely advanced periodontitis, careful planning and execution of treatment ensures that the disease does not continue to progress and the integrity of the dentition is maintained. PMID- 7867861 TI - Dental specialists in the future. PMID- 7867862 TI - The future of general dental practice. PMID- 7867863 TI - An introduction to indices of malocclusion. AB - Orthodontic indices have been used for many years to assess the severity of a patient's malocclusion and hence determine the need for treatment. Two indices- the Index of Orthodontics Treatment Need (IOTN) and the Peer Assessment Rating (PAR) Index--have recently been developed. The use of indices is likely to become more widespread in the future so that more uniformity is achieved in assessing need for treatment and its success. This article describes how the two indices are applied. PMID- 7867864 TI - Treatment of a Bowling Green related injury. AB - Bowling green related injuries are rare. In this case study, the author describes a lucky escape from extensive facial injury for a young man. PMID- 7867865 TI - Psychological aspects of patient management in dental practice. AB - Failure to achieve good patient management will result in poor patient co operation and potential failure of treatment. In this article, ways of establishing and maintaining good communication between the dental team and the patient are discussed. PMID- 7867866 TI - The aetiology and management of localized anterior tooth wear in the young adult. AB - This article reviews the aetiology and clinical features of the increasingly common problem of localized loss of anterior tooth tissue in the young adult. The management of the problem is highlighted, with emphasis placed on preservation of the tooth structure and the use of modern materials and techniques. PMID- 7867867 TI - Stress in dental school: a survey of students. AB - The authors set up a study to investigate the levels of stress experienced by dental students and the students' perceptions of the sources of stress. Levels of stress among students were found to be high, particularly during the first 2 years of dental school. Sources of stress included the practice of conservative dental surgery, dealing with administration and dealing with clinical demonstrators. PMID- 7867868 TI - A low-cost, portable removable prosthodontic treatment system for the compromised elderly. AB - The elderly population (people of 65 years and older), especially the compromised elderly, places an overwhelming demand on the health care system in the USA. Dentists must provide services to all segments of the elderly population, but the compromised elderly are labelled as 'poor' candidates for dental treatment because they are unlikely to cooperate, find it difficult to get to the dental surgery, or cannot pay for professional services. The authors of this paper have developed guidelines for on-site patient management using a team approach and a low-cost, portable treatment system for providing removable prosthodontic services using ligh-cured denture resin. The system is cost-effective, reduces chairside time and requires minimal patient cooperation but does not compromise the quality of care. Treatment can be provided in non-traditional settings with family members and support staff on-hand. The feasibility of this approach has been demonstrated by its use in hospitals, clinics, nursing homes and private residences. PMID- 7867869 TI - Inhibitory effect of gabexate mesilate on human neutrophil function. AB - Neutrophils accumulated in the lung are thought to play a key role in the pathogenesis of adult respiratory distress syndrome and interstitial pneumonia following bone-marrow transplantation. The effects of gabexate mesilate on several aspects of human neutrophil function have been investigated. Gabexate mesilate significantly decreased both the generation of reactive oxygen species (O2-, H2O2, OH.) by neutrophils and neutrophil chemotaxis. In contrast, the drug did not affect the levels of reactive oxygen species generated by a cell-free reactive-oxygen-species generating system. Intracellular calcium concentrations in neutrophils stimulated by f-Met-Leu-Phe were decreased in the presence of gabexate mesilate. These data suggest that the reduction in reactive-oxygen species production and neutrophil chemotaxis by gabexate mesilate may contribute to the effectiveness of the drug in adult respiratory distress syndrome and interstitial pneumonia after bone-marrow transplantation. The suppression of the increase in intracellular calcium concentration may at least be responsible for the inhibition of these neutrophil functions by gabexate mesilate. PMID- 7867870 TI - Influence of dietary composition on the inhibition of fat absorption by orlistat. AB - Orlistat, a potent and selective inhibitor of gastrointestinal lipases, is designed for the treatment of obesity. The effect of orlistat on dietary fat absorption, when it was administered with diets differing in fibre content (high and low) and accessibility of fat (intra- and extracellular fat), was investigated in 32 hospitalized healthy males, according to an open, two factorial study design. The subjects were randomly allocated to one of four parallel groups of equal size: A = intracellular fat, high fibre (28 g/day); B = extracellular fat, high fibre; C = extracellular fat, low fibre (9 g/day); or D = intracellular fat, low fibre. After a 5-day run-in period to accustom the volunteers to the standardized diet (2500 kcal and 84 g fat per day) and to establish baseline faecal fat parameters, they received 80 mg orlistat, three times daily mid-way through each meal for 8 days. Faeces were collected to measure total fat and free fatty acid excretions. The mean baseline-corrected excretion (% of dietary fat) in groups A, B, C and D, respectively, was 37.0, 30.4, 30.3 and 34.5 for total fat, and 6.5, 4.3, 2.6 and 3.9 for free fatty acids. The 95% confidence intervals for the difference between the means for high fibre and low fibre groups and for intracellular fat and extracellular fat groups, respectively, were 1.4 +/- 4.9 and 5.5 +/- 4.9 for total fat, and 2.2 +/- 3.1 and 1.9 +/- 3.1 for free fatty acids. The statistically significant difference (P < 0.05) in total faecal fat between intracellular fat and extracellular fat groups, in absolute terms < 5 g fat/day, was not regarded as clinically relevant. Under the conditions of this study, dietary fibre content and accessibility of fat had no relevant effect on the inhibition of fat absorption by orlistat. PMID- 7867871 TI - Patient compliance with once-daily and twice-daily oral formulations of 5 isosorbide mononitrate: a comparative study. AB - This study compares patient compliance with once- and twice-daily formulations of 5-isosorbide mononitrate. A total of 31 patients (20 men and 11 women) with stable angina pectoris were randomized to receive either 60 mg 5-isosorbide mononitrate in a controlled release formulation once daily, or 20 mg 5-isosorbide mononitrate twice daily. The results indicated that compliance assessed using the electronic Medication Event Monitoring System (MEMS) was better with the once daily than with the twice-daily formulation; patients on the once-daily regimen performed better with respect to the total number of bottle openings, the number of openings per day, the timing of openings and the intervals between openings. The apparently superior compliance with the once-daily regimen appeared to be reflected in better efficacy; patients on the once-daily regimen experienced fewer angina attacks (a mean of 1.7 per 7 days, compared with 3.3 per 7 days for patients on the twice-daily regimen) and used fewer nitroglycerin tablets than those on the twice-daily regimen. PMID- 7867872 TI - Twice-weekly dosing for thyroxine replacement in elderly patients with primary hypothyroidism. AB - Seven female patients (mean age 86 years) with proven biochemical primary hypothyroidism were enrolled in a single-blind randomized crossover study, of standard daily versus twice-weekly thyroxine therapy, with each phase of one month's duration. The median daily dose of thyroxine was 100 micrograms (range 75 100 micrograms). Serum levels of thyroid hormones and thyrotrophin were very similar during twice-weekly thyroxine therapy to those during daily therapy and there were no statistically significant differences between trough and peak serum total triiodothyronine, free thyroxine, or thyrotrophin levels or systolic time intervals during twice-weekly thyroxine. Administration of thyroxine twice-weekly to elderly patients with primary hypothyroidism gives effective biochemical thyroid hormone replacement, with no evidence from the systolic time intervals of tissue thyrotoxicosis at expected peak thyroid hormone concentrations. Supervised twice-weekly thyroxine should be considered in patients with primary hypothyroidism who comply poorly with daily dosing. PMID- 7867873 TI - Patient compliance and therapeutic coverage: amlodipine versus nifedipine (slow release) in the treatment of angina pectoris. Belgian Collaborative Group. AB - Patient compliance with therapy is often poor and overestimated by the treating physician; it is particularly important in cardiovascular diseases such as hypertension and angina pectoris. Compliance was studied in an open parallel study in out-patients with stable angina pectoris, given either amlodipine (5 mg, once daily) or slow-release nifedipine (20 mg, twice daily) for 12 weeks. Compliance was assessed using pill counting and using an electronic device, the medication event monitoring system, to record the time and date of each opening and closure of the pill container. There was no difference between the two groups in pill count or in 'taking compliance' (the percentage of prescribed doses taken as indicated by the monitoring system). Compliance was significantly better (P < 0.001) with amlodipine, however, for 'correct dosing' (the percentage of days on which the correct dose was taken) and for 'timing compliance' (the percentage of doses taken at the prescribed time interval after the last dose). 'Therapeutic coverage' (the estimated proportion of treatment time for which the drug was active) was also significantly better for amlodipine (P < 0.001). There was no difference in reported side-effects between the two therapies. PMID- 7867874 TI - No effect of cloricromen on some coagulation parameters in patients with ischaemic cerebrovascular disease. AB - Cloricromen is a new drug that inhibits platelet aggregation in man and in experimental thrombosis. Twenty patients with a history of atherothrombotic stroke received cloricromen (100 mg, twice daily) for 30 days in order to evaluate its effects on plasma fibrinogen, antithrombin III, and other variables of the haemostatic system. A statistically significant decrease in the prothrombin time (P < 0.01) was found only after 30 days of therapy. This decrease was transient and disappeared 15 days after the end of treatment. No statistically significant changes in plasma fibrinogen levels, antithrombin III, partial thromboplastin time, or platelet count were observed compared with baseline values. No side-effects were reported. This study did not reveal an effect of cloricromen on coagulative variables in patients with cerebrovascular occlusive disease. PMID- 7867875 TI - Acceleration of phagocytosis in human neutrophils incubated with gabexate mesilate. AB - It has recently been shown that gabexate mesilate inhibited human neutrophil functions including chemotaxis and reactive oxygen species production. In the present study, the effects of gabexate mesilate on phagocytosis by human neutrophils in vitro were investigated. Gabexate mesilate significantly enhanced neutrophil phagocytosis in a dose-dependent manner. This characteristic of gabexate mesilate may facilitate protection against infecting micro-organisms, although the inhibition of reactive oxygen species production by neutrophils may be a disadvantage for host-defense against infection. PMID- 7867877 TI - International Conference on Ulcer Research, 8th meeting. Kyoto, Japan, November 20-23, 1994. Abstracts. PMID- 7867876 TI - Association between myotonic dystrophy and primary hyperparathyroidism. AB - A case of primary hyperparathyroidism in a patient with myotonic dystrophy is reported. A 56-year old female with myotonic dystrophy, admitted to hospital with a urinary tract infection, had widespread muscle atrophy and myotonia with bilateral cataracts. Biochemical findings of normal renal function but raised blood calcium, depressed blood phosphate and increased parathyroid hormone, were consistent with a diagnosis of primary hyperparathyroidism. Thallium scanning of the parathyroids showed an area of discordant thallium suggesting a parathyroid adenoma. When the left lower parathyroid was later excised, histology was consistent with the diagnosis of parathyroid adenoma. As far as the authors are aware this is the first report of myotonic dystrophy and primary hyperparathyroidism in the same patient. PMID- 7867878 TI - Tissue-specific correction of lipogenic enzyme gene expression in diabetic rats given vanadate. AB - Vanadium is a potent insulinomimetic agent. In vivo, its blood glucose lowering action in insulin-deficient diabetic rats is associated with corrected expression of genes involved in hepatic glucose metabolism. In this study, we investigated whether vanadate treatment also reverses the impaired expression of genes coding for key enzymes of lipogenesis in diabetic liver and white adipose tissue. Oral administration of vanadate to streptozotocin-rats caused a 55% fall in plasma glucose levels after feeding without modifying low insulinaemia. It also partially corrected the low thyroid hormone concentrations. In untreated diabetic animals, hepatic mRNA levels of acetyl-CoA carboxylase and fatty acid synthase were reduced by more than 80 and 90%, respectively, in close correlation with changes in enzyme activities. Three weeks of vanadate treatment totally restored acetyl-CoA carboxylase mRNA and partially restored fatty acid synthase mRNA (71% of control levels). The activities of both lipogenic enzymes were increased 3.5 to 4-fold, to reach 45 to 65% of control values. By contrast, in white adipose tissue, vanadate modified neither expression nor activity of both lipogenic enzymes, which remained blunted (< 10% of control levels). In conclusion, vanadate treatment partially restores the activities of two key lipogenic enzymes in liver, but not in white adipose tissue, of diabetic rats. This correction results from a reversal of impaired pre-translational regulatory mechanisms possibly mediated by an improvement of thyroid function and a selective restoration of liver glycolytic flux. PMID- 7867879 TI - Reduced sensitivity of dihydroxyacetone on ATP-sensitive K+ channels of pancreatic beta cells in GK rats. AB - In the GK (Goto-Kakizaki) rat, a genetic model of non-insulin-dependent diabetes mellitus, glucose-induced insulin secretion is selectively impaired. In addition, it has been suggested by previous studies that impaired glucose metabolism in beta cells of the GK rat results in insufficient closure of ATP-sensitive K+ channels (KATP channels) and a consequent decrease in depolarization, leading to a decreased insulin release. We have recently reported that the site of disturbed glucose metabolism is probably located in the early stages of glycolysis or in the glycerol phosphate shuttle. In the present study, in order to identify the impaired metabolic step in diabetic beta cells, we have investigated insulin secretory capacity by stimulation with dihydroxyacetone (DHA), which is known to be directly converted to DHA-phosphate and to preferentially enter the glycerol phosphate shuttle. In addition, using the patch-clamp technique, we also have studied the sensitivity of DHA on the KATP channels of beta cells in GK rats. The insulin secretion in response to 5 mmol/l DHA with 2.8 mmol/l glucose was impaired, and DHA sensitivity of the KATP channels was reduced in beta cells of GK rats. From these results, we suggest that the intracellular site responsible for impaired glucose metabolism in pancreatic beta cells of GK rats is located in the glycerol phosphate shuttle. PMID- 7867880 TI - Beta-cell proliferation in normal and streptozotocin-treated newborn rats: site, dynamics and capacity. AB - Regeneration of neonatal beta cells after streptozotocin (STZ)-induced destruction may be due to either replication from pre-existing intra-islet beta cells or extra-islet precursor cells. To further investigate this issue, beta cell growth was analysed in normal and streptozotocin-treated newborn rats (100 micrograms/g body weight) at several time points during the first 20 days of life. Beta cells were identified by insulin immunostaining, non-isotopic in situ hybridization for rat preproinsulin mRNA, and electron microscopy. Their proliferative activity was recorded by bromodeoxyuridine-pulse labelling. Beta cell size and total volume were determined by computerized morphometry. In normal rats, there was a threefold increase in total beta-cell volume during the first 5 days of life, with no further expansion till day 20. The bromodeoxyuridine labelling index of the intra-islet beta cells was smaller than that of the extra islet beta cells (2-3% vs 15-20%). Comparison of the cell birth rate, calculated from the beta-cell labelling index, with the observed increase in beta-cell volume suggested that in normal neonatal rats proliferation of the intra-islet beta-cell population could account for only 10% of the observed expansion. Administration of streptozotocin at birth resulted in more than 90% reduction of the total beta-cell volume at day 2 which then increased to 39% of the normal value by day 20. During this period of partial regeneration, which restored normoglycaemia, the labelling index of intra-islet beta cells was higher than in normal rats (9% vs 2%, p < 0.001), whereas no change was seen in the extra-islet beta-cell labelling index.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867881 TI - Expression of human GLUT4 in mice results in increased insulin action. AB - Glucose metabolism was evaluated in transgenic mice expressing the human GLUT 4 glucose transporter. Fed GLUT 4 transgenic mice exhibited a 32% and 56% reduction in serum glucose and insulin and a 69% and 33% increase in non-esterified fatty acid and lactate levels, respectively. Transgenic mice exhibited a significant increase in whole-body glucose disposal during a euglycaemic-hyperinsulinaemic clamp. Insulin-stimulated glucose uptake in isolated soleus muscles and adipocytes was greater in transgenic compared to control mice due to increased basal glucose uptake. Transgenic mice displayed increased glycogen levels in liver and gastrocnemius muscle, and increased insulin-stimulated 14C-glycogen accumulation in isolated soleus muscle. We conclude that over-expression of the GLUT 4 glucose transporter in mice results in 1) an increase in whole-body glucose disposal and storage, and 2) an increase in both basal and insulin stimulated glucose uptake and disposal in vitro. These changes resulted in the reduction of serum glucose and insulin levels. These results provide direct evidence that glucose transport (and GLUT 4 per se) plays a significant role in regulating whole-body glucose homeostasis. Additionally, these data support the idea that pharmacological strategies directed at increasing the expression of GLUT 4 protein may have beneficial (hypoglycaemic) effects in the diabetic state. PMID- 7867882 TI - Inheritance of MHC class II genes in IDDM studied in population-based affected and control families. AB - The transmission of HLA-DR and DQ was compared between 46 families with at least one child affected by insulin dependent diabetes mellitis (IDDM) and 43 healthy control families. In the patient families, there was an increased transmission of DR4 (p < 0.025) and DQB1*0302 (p < 0.01) from both parents to the index patient. There was an increased transmission of DQB1*0302 (p < 0.03) from the mothers only. The non-inherited maternal haplotypes showed a significantly decreased frequency (p < 0.01) of positively associated haplotypes (DR4-DQA1* 0301 DQB1*0302, DR3-DQA1*0501-DQB1*0201) compared to all parental haplotypes in the control families. In the control families neither transmission rates nor frequencies of non-inherited haplotypes differed from those expected in the control families. In conclusion, the observed reduction of IDDM-positively associated haplotypes in patient non-inherited maternal haplotypes, but not in non-inherited paternal haplotypes, suggests that tolerance during fetal life to maternal non-inherited HLA molecules may be important to diabetes development. PMID- 7867883 TI - Anti-glutamate decarboxylase and other antibodies at the onset of childhood IDDM: a population-based study. AB - Sera obtained at diagnosis from 273 children (0-14 years) with insulin-dependent diabetes mellitus (IDDM) were studied to compare different autoantibody levels. The subjects comprise 75% of all incident cases in New South Wales, Australia, for a 2-year period (ascertainment > 99% complete). Antibodies against glutamate decarboxylase were measured by radioimmunoprecipitation, insulin autoantibodies (on 176 sera collected within 4 days of initiation of insulin therapy) by radioimmunoassay, thyroid peroxidase and antigliadin IgA antibodies by enzyme linked immunoassay, and anti-endomysial IgA and islet cell antibodies by indirect immunofluorescence. Reference ranges for anti-glutamate decarboxylase and insulin autoantibodies were determined in a group of non-diabetic children. Of the sera 69% were positive for anti-glutamate decarboxylase, 65% for insulin autoantibodies, 71% for islet cell antibodies (> or = 20 Juvenile Diabetes Foundation units), 10% for anti-thyroid peroxidase, 2.6% for antigliadin and 3.0% for anti-endomysial antibodies. Islet cell antibodies and insulin autoantibodies were both negative in 13.7% of the sera, while only 5.8% were negative for all three of islet cell antibodies, insulin autoantibodies and anti-glutamate decarboxylase. There was a higher frequency of anti-glutamate decarboxylase among girls than boys (75% vs 63%, p = 0.03) and a negative correlation between the level of insulin autoantibodies and age at diagnosis (r = -0.41, p < 0.0001). A higher frequency of antithyroid peroxidase was found with increasing age (p = 0.05). Higher titres of islet cell antibodies were associated with a higher frequency of both anti-glutamate decarboxylase (p < 0.0001) and insulin autoantibodies (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867884 TI - Oscillations in cytoplasmic free calcium concentration in human pancreatic islets from subjects with normal and impaired glucose tolerance. AB - Plasma insulin levels in healthy subjects oscillate and non-insulin-dependent diabetic patients display an irregular pattern of such oscillations. Since an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) in the pancreatic beta cell is the major stimulus for insulin release, this study was undertaken to investigate the dynamics of electrical activity, [Ca2+]i-changes and insulin release, in stimulated islets from subjects of varying glucose tolerance. In four patients it was possible to investigate more than one of these three parameters. Stimulation of pancreatic islets with glucose and tolbutamide sometimes resulted in the appearance of oscillations in [Ca2+]i, lasting 2-3 min. Such oscillations were observed even in some islets from patients with impaired glucose tolerance. In one islet from a diabetic patient there was no response to glucose, whereas that islet displayed [Ca2+]i-oscillations in response to tolbutamide, suggesting that sulphonylurea treatment can mimic the complex pattern of glucose-induced [Ca2+]i-oscillations. We also, for the first time, made patch-clamp recordings of membrane currents in beta-cells in situ in the islet. Stimulation with glucose and tolbutamide resulted in depolarization and appearance of action potentials. The islet preparations responded to stimulation with a number of different secretagogues with release of insulin. The present study shows that human islets can respond to stimulation with glucose and sulphonylurea with oscillations in [Ca2+]i, which is the signal probably underlying the oscillations in plasma insulin levels observed in healthy subjects. Interestingly, even subjects with impaired glucose tolerance had islets that responded with oscillations in [Ca2+]i upon glucose stimulation, although it is not known to what extent the response of these islets was representative of most islets in these patients. PMID- 7867885 TI - Alterations of lymphocyte subsets in children of diabetic mothers. AB - To investigate the impact of diabetic mothers on the maturation of the immune system in their offspring, immunophenotypic markers of major lymphocyte subpopulations were evaluated by two-colour flow cytometric analysis in 160 healthy children of diabetic mothers (100 with insulin-dependent diabetes mellitus (IDDM): 48 with gestational diabetes), including 22 neonates, 45 infants aged 8-12 months, 46 children aged 1-2 years, 29 children aged 3-6 years and 18 children aged 7-17 years. Results were compared with 21 neonates of healthy mothers from our hospital and with 110 paediatric subjects of a reference population. In neonates of diabetic mothers, percentages of total lymphocytes (p = 0.044), T and B lymphocytes (p = 0.004, respectively) were significantly decreased compared to our neonates of healthy mothers. By subdividing the group of neonates in offspring of mothers with IDDM (n = 15) or gestational diabetes (n = 7), differences compared to normal neonates were mainly observed in neonates of mothers with IDDM (T lymphocytes: p = 0.006; B lymphocytes: p = 0.008). In cord blood, 45.5% of neonates had antibodies to islet cells, insulin or glutamic acid decarboxylase, most likely transmitted through the placenta of the diabetic mother. No association was found between alterations of lymphocyte subsets and antibody-positivity in cord blood, nor was there any correlation of lymphocyte counts and mean HbA1 during pregnancy, maternal age at delivery, diabetes duration, or neonatal birth weight, respectively. Comparisons among age groups from newborn infants through adolescents revealed higher percentages of total lymphocytes and lower percentages of activated T cells in children of diabetic mothers compared to children of the reference population between the age of 1 to 6 years (67-73% of the cases above and 62-77% below the interquartiles of the reference range, respectively). No significant differences in lymphocyte subpopulations between children of mothers with IDDM diabetes and gestational diabetes have been detected. In addition, there were no abnormalities of lymphocyte subsets in children who are at high risk for the development of IDDM. In summary, we suggest that the observed changes in children of diabetic mothers may reflect a cellular immune reaction to the particular maternal environment, characterized by both an abnormal metabolic state and persisting autoimmunity in the affected mother. PMID- 7867886 TI - Immunoassay of platelet-derived growth factor in the blood of patients with diabetes mellitus. AB - Platelet-derived growth factor (PDGF) is a powerful mitogen for many cell types, and is believed to play a major role in wound healing when released from platelets at sites of injury. In diabetes mellitus, it has been proposed that premature release of PDGF from platelets impairs the ability of platelets to initiate healing, and also accelerates the development of diabetic complications such as angiopathy by increasing plasma-borne PDGF. However, plasma samples from diabetic patients have not previously been assayed for PDGF using suitable techniques. A sensitive monoclonal enzyme-linked immunoassay for PDGF was applied to plasma and serum samples from 18 healthy control subjects and 60 diabetic patients. Neither plasma nor serum PDGF concentrations differed significantly between control subjects, insulin-dependent, and non-insulin-dependent diabetic patients. However, 23% of the diabetic subjects had serum PDGF levels above the control range. Limited joint mobility, which is characterised by joint contractures and collagen deposition in the skin, and is associated with microvascular disease, was used as a marker of diabetic complications. Limited joint mobility affected 43% of the diabetic subjects. Patients with moderate limited joint mobility had had diabetes significantly longer than those without limited joint mobility (means 17 years and 9 years, respectively, p = 0.008). However, limited joint mobility was not associated with elevated serum or plasma PDGF in insulin-dependent or non-insulin-dependent diabetes. We conclude that complications of diabetes are unlikely to be caused by changes in systemic levels of PDGF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867887 TI - Transphosphatidylation of sugar alcohols and its implications for the pathogenesis of diabetic complications. AB - Glucose-induced sorbitol accumulation and attendant alterations in cellular myo inositol and phosphoinositide metabolism have been invoked in the pathogenesis of diabetic complications; however, direct effects of sorbitol on membrane phospholipid composition or metabolism have never been evaluated. Phospholipase D catalyses the transphosphatidylation of ethanol into phosphatidylcholine to yield phosphatidylethanol, an "abnormal" phospholipid whose content in rat brain is increased by chronic ethanol ingestion. Analogous transphosphatidylation of sorbitol or other polyols whose concentration is elevated in diabetes was explored in vitro and in glucose-exposed cultured human retinal pigment epithelial cells. Phosphatidylcholine and varying concentrations of sorbitol, galactitol, mannitol and glucose were incubated with peanut phospholipase D in sodium acetate buffer for varying time periods. Thin layer chromatography revealed new phospholipid bands whose hydrolysis by phospholipase D liberated a water-soluble compound that cochromatographed with sorbitol on gas-liquid chromatography, and whose concentration increased in a time- and concentration dependent fashion. Identical transphosphatidylation activity was demonstrated in a rat brain synaptosomal fraction. Phospholipase D hydrolysis of lipids from human retinal pigment epithelial cells constitutively overexpressing the aldose reductase gene yielded a sorbitol-like compound whose appearance was increased by glucose exposure and was decreased by an aldose reductase inhibitor. Thus, glucose-induced aldose reductase inhibitor sensitive sorbitol accumulation might induce the formation of "phosphatidylsorbitol" through a transphosphatidyl mechanism that may contribute to altered membrane phospholipid metabolism in diabetes. PMID- 7867888 TI - Association of polymorphism in the interferon gamma gene with IDDM. AB - Cytokines may play important roles in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). We analysed a dinucleotide repeat polymorphism within the first intron of the interferon gamma (IFN-gamma) gene in Japanese diabetic patients (175 IDDM and 145 non-insulin-dependent diabetes mellitus) and 267 control subjects. A significant difference was observed in the global allele distribution of the polymorphism between the IDDM and control groups (p = 0.039). The difference from the control group was more evident in the patients whose insulin therapy started within 1 year from onset (p = 0.006) or in the young onset (< 10 years) patients (p = 0.0006). The alleles "3" and "6" were increased in the IDDM patients, and a significant increase in the frequency of the "3/6" genotype was observed in the IDDM patient group (9.1%, RR 2.9, p = 0.010), in the patients with initial insulin therapy less than 1 year from onset (10.6%, RR 3.4, p = 0.004), or in the young-onset patients (16.7%, RR 5.7, p = 0.0003) in comparison to the control subjects (3.4%). There was a tendency towards frequent occurrence of clinical characteristics which reflect young or abrupt onset of diabetes or both, and depletion of insulin secretion capacity in the patients with "3/6" or "6/6" in comparison to the patients with other genotypes. These results suggest that the IFN-gamma gene region may contribute to the pathogenesis of IDDM and could be a genetic marker for IDDM. PMID- 7867889 TI - Potent glycogenic effect of GLP-1(7-36)amide in rat skeletal muscle. AB - GLP-1(7-36)amide is an intestinal post-translational proglucagon product released mainly after carbohydrate ingestion, the glucose dependent insulinotropic and antidiabetogenic actions of which have been documented. In this work, by exploring whether GLP-1(7-36)amide has any effect on the glucose metabolism of the muscle, we have observed that this peptide, at physiological concentrations, exerts in this tissue an increment of the D-[U-14C]glucose incorporated into glycogen, which is accompanied by an increase in the glycogen synthase a activity; also, it stimulates both glucose oxidation and lactate formation. These data indicate that the skeletal muscle is one of the target tissues for GLP-1(7 36)amide, where its insulin-like effect explains, at least in part, its plasma glucose lowering action; thus, GLP-1(7-36)amide may well be implicated in the physiological control of glucose homeostasis after meals, not only by acting as an incretin, but also by directly promoting glucose disposal. PMID- 7867890 TI - Endothelial dysfunction and diabetic angiopathy. PMID- 7867891 TI - Autonomic neuropathy: comparison of two screening procedures. PMID- 7867892 TI - Prevalence of maternally inherited diabetes and deafness in diabetic populations in The Netherlands. PMID- 7867893 TI - Chondrogenesis of neural crest cells: effect of poly-L-lysine and bone extract. AB - The mechanisms of chondrogenic differentiation are generally studied in vitro by analyzing the action of agents that promote or affect chondrogenesis in embryonic mesenchyme, such as cells of the embryonic limb bud. However, it is not known whether progenitor cells of the craniofacial skeleton, which are of a different embryonic origin and derived from the neural crest, are similarly responsive to such agents. To gain insight into the regulation of chondrogenic differentiation in cells derived from neural crest, we have treated chick embryonic neural crest explants in vitro with poly-L-lysine (PL, M(r) 380 kDa) or bovine bone extract (BBE), two agents known to enhance chondrogenesis of limb mesenchymal cells. Both cephalic (normally chondrogenic) and trunk (normally nonchondrogenic) neural crest cells were analyzed. Chondrogenic differentiation was determined by histological, immunohistochemical and autoradiographic methods. Our results indicate that both PL (380 kDa) and BBE significantly enhance chondrogenesis of cephalic neural crest cells, suggesting that the mechanism of chondrogenesis of these ectodermally derived cells is similar to that of mesodermally derived limb mesenchymal cells. However, trunk neural crest cells did not undergo chondrogenesis in response to PL or BBE. These data show that chondrogenesis can be enhanced in cranial ectodermal neural crest cells in a manner similar to that in the limb mesenchyme. However, since nonchondrogenic trunk neural crest cells are not responsive, an inherent potential for cartilaginous differentiation is necessary for exogenous stimulation of chondrogenesis. PMID- 7867894 TI - Expression of the alpha 2-subunit of laminin correlates with increased cell adhesion and metastatic propensity. AB - Previous studies have indicated that laminin from neoplastic cells of high tumorigenicity is less active in promoting cell adhesion than aminin from normal cells or tissues. In the present study, we tested the hypothesis that laminin of metastatic tumor cells differs from that of nonmetastatic cells. Accordingly, we determined the subunit composition of laminin in highly metastatic, ras transformed cells (4R) and compared it with laminin produced by nonmetastatic cells transformed with ras plus E1a (RE4). Metastatic 4R cells produced three to four times more of the alpha 2-subunit of laminin than RE4 cells did. Furthermore, the highly metastatic human melanoma cells (1205 and A2058) made and secreted into the medium, laminin containing significantly more of the alpha 2 subunit than laminin from the highly tumorigenic but nonmetastatic melanoma WM793 or HT1080 fibrosarcoma cells. Using HT1080 cells, laminin (250 ng/well) from 4R cells showed more adhesion promoting activity (68%) than laminin from RE4 cells (39%). Similarly, laminin isolated from human placenta, which expresses both the alpha 1 beta 1 gamma 1 and alpha 2 beta 1 gamma 1 isoforms, promoted cell adhesion better (63%) than EHS laminin (26%), which contains only the former isoform, at 250 ng/well. In addition, both 4R and RE4 cells attached more efficiently to 4R laminin-coated substratum than to RE4 laminin at 0.3 and 0.6 microgram/well.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867895 TI - Effects of chronic electrical stimulation on myosin heavy chain expression in satellite cell cultures derived from rat muscles of different fiber-type composition. AB - Myotube cultures were established from satellite cells of three rat muscles of different fiber-type composition, slow-twitch soleus, diaphragm, and fast-twitch tibialis anterior (TA). Effects of chronic electrical stimulation were studied by exposing these cultures for up to 13 days to a stimulus pattern consisting of 250 ms impulse trains of 40 Hz, repeated every 4 s. Changes in myosin expression were assessed at the mRNA level by Northern blotting and in situ hybridization. Expression of slow myosin at the protein level was analysed by immunoblotting and immunohistochemistry with two antibodies, one specific to adult slow myosin, the other reacting with developmental and adult slow myosin heavy chain (MHCI) isoforms. In all three myotube cultures stimulation enhanced the mRNA and protein expression of a developmental isoform of slow myosin (MHCI). However, the three myotube cultures differed in the extent of the increase in MHCI. It was greatest in soleus-derived myotubes, least in TA-derived myotubes, and intermediate in diaphragm-derived myotubes. In addition to the increase in slow myosin, long-term stimulation led to an isoform switch, as indicated by an increase in myotubes reacting with the antibody specific for the adult MHCI. Our results suggest that enhanced contractile activity promotes the expression of the slow phenotype predetermined in satellite cells of slow-twitch, type I fibers. The different extents of increased slow myosin expression may thus be explained as reflecting different percentages of type I fibers and consequently of slow-type satellite cells in the corresponding donor muscles. PMID- 7867896 TI - Retinoic acid prevents downregulation of ras recision gene/lysyl oxidase early in adipocyte differentiation. AB - Adipocyte differentiation of 3T3-L1 cells is a complex process which is inhibited by retinoic acid (RA). Since RA acts by nuclear receptors which directly regulate gene expression, we postulate that the primary targets of RA action in this system are genes which are regulated early in adipose conversion. In this study, we demonstrate the use of the differential display technique to search for early events in adipose commitment which are sensitive to RA. A mRNA was identified on the basis of its RA-dependent gene expression 24 h after initiation of a standard differentiation protocol. Molecular cloning of the cDNA revealed it to be identical to the ras recision gene (rrg), for lysyl oxidase. Indeed, two mRNAs identical to those recognized by lysyl oxidase probes were expressed in preadipocytes and tandemly repressed with 24 h of exposure to differentiation conditions. Lysyl oxidase activity was similarly reduced in the media of differentiated cells. RA completely blocked the differ-entiation-related reduction in rrg/lysyl oxidase gene expression, although RA had no independent stimulatory effect on rrg/lysyl oxidase expression in cells not exposed to differentiating conditions. Thus, differential display has been successfully used to identify rrg/lysyl oxidase as an early marker for adipose conversion that is responsive to RA. PMID- 7867897 TI - How intestinal epithelial cell differentiation inhibits the cell-entry of Yersinia pseudotuberculosis in colon carcinoma Caco-2 cell line in culture. AB - In the human intestine, target cells of enteropathogens differentiate during cell migration along the crypt-villus axis. We have recently provided evidence that intestinal cell differentiation up-regulates intestinal cell infection by the noninvasive enterotoxigenic Escherichia coli [5, 23]. Several enterovirulent bacteria can penetrate intestinal epithelial cells, which are normally nonphagocytic. To document the role of intestinal epithelial cell differentiation in the pathogenesis of enteroinvasive bacteria, we examined here the intestinal cell-association and cell-entry of Yersinia pseudotuberculosis as a function of cell differentiation. For this purpose we used the colon carcinoma Caco-2 cell line in culture, which provides the most useful tool for the study of intestinal epithelial cell differentiation, because of its unique ability to spontaneously differentiate upon reaching confluence in normal culture condition. We report here that the thermoregulated inv and ail loci of Y. pseudotuberculosis have distinct roles in infection of Caco-2 cells. The ail locus initiates the cell association and the inv locus initiates both the cell-association and the cell entry processes. Moreover, we observed that: (i) both the bacterial cell association (ail) and the bacterial cell-invasion (inv) occur at subconfluence when the Caco-2 cells are undifferentiated, and (ii) these processes are arrested when the differentiation commences. Since the integrin-beta 1 heterodimers are involved in cell-entry of Y. pseudotuberculosis in several mammalian cells, we further examined which beta 1 integrin promotes bacterial cell-entry in Caco-2 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867898 TI - Noncancer risk assessment. PMID- 7867899 TI - Dose-response assessment for developmental toxicity. I. Characterization of database and determination of no observed adverse effect levels. AB - Developmental toxicity risk assessment currently relies on the estimation of reference doses (RfDDTs) or reference concentrations (RfCDTS) based on the use of no observed adverse effect levels (NOAELs) and uncertainty factors. The benchmark dose (BMD) has been proposed as an alternative basis for reference value calculations. A large database of 246 developmental toxicity experiments (Segment II-type studies) representing 1825 data subsets for various endpoints was compiled for use in comparing NOAEL and BMD approaches to developmental toxicity risk assessment. This paper describes the characteristics of the database used and the estimation of NOAELs using several approaches. For each endpoint evaluated, two NOAELs were calculated using the NOSTASOT procedure (Tukey et al., 1985). The first NOAEL calculation, the QNOAEL, was based on a quantal response where a litter was defined as "affected" if one or more fetuses or implants in the litter had the endpoint of interest. The second NOAEL calculation, the CNOAEL, was based on the proportion of fetuses or implants affected within each litter and was treated as a continuous response variable. Fifty-seven percent of the 246 experiments had at least one endpoint that showed a significant trend with dose. A total of 386 data sets were significant with respect to both the quantal and continuous test of trend. An additional 44 data sets were identified with significant trend only by the quantal approach whereas 177 additional data sets were identified with significant trend tests only by the continuous approach. Thus, the continuous approach appeared to be more powerful in detecting dose-related toxicity, but the patterns detected by the two approaches differed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867900 TI - Dose-response assessment for developmental toxicity. II. Comparison of generic benchmark dose estimates with no observed adverse effect levels. AB - Developmental toxicity risk assessment currently relies on the estimation of reference doses (RfDDTS) of reference concentrations (RfCDTS) based on the use of no observed adverse effect levels (NOAELS) divided by uncertainty factors (UFs). The benchmark dose (BMD) has been proposed as an alternative basis for reference value calculations. A large database of 246 developmental toxicity experiments representing 1825 endpoints related to dead implants or malformed fetuses has been compiled for use in evaluating alternative approaches to developmental toxicity risk assessment. Using this database we have compared two approaches for BMD estimation with each other and with corresponding statistically derived NOAELS. Comparisons have been based on proportion of affected litters (litters with one or more affected offspring, a quantal response variable) and on the proportion of affected offspring within each litter (a continuous response variable). A quantal Weibull model was used to calculate generic BMDs for the quantal response variable (QBMDs) and a continuous power model was used to calculate generic BMDs for the continuous response variable (CBMDs) at three levels of additional risk (10, 5, and 1%). CBMD05s (continuous benchmark doses for 5% risk) and CNOAELs (statistically derived NOAELs based on the continuous response variable) were similar, with over 98% of the data subsets having CBMD05 and CNOAEL values that differed by less than an order of magnitude. In contrast, QNOAELs tended to be greater than corresponding QBMD10s. The observed conservatism of the QBMD values relative to the corresponding CBMD values was attributed to two factors, lower maximum likelihood estimates for the quantal model and wider confidence intervals around the maximum likelihood estimates, compared to the continuous model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867901 TI - Dose-response assessment for developmental toxicity. III. Statistical models. AB - Although quantitative modeling has been central to cancer risk assessment for years, the concept of dose-response modeling for developmental effects is relatively new. The benchmark dose (BMD) approach has been proposed for use with developmental (as well as other noncancer) endpoints for determining reference doses and reference concentrations. Statistical models appropriate for representing the unique features of developmental toxicity testing have been developed and applied (K. Rai and J. Van Ryzin, 1985, Biometrics 41, 1-9; L. Kupper, C. Portier, M. Hogan, and E. Yamamoto, 1986, Biometrics 42, 85-98; R. Kodell, R. Howe, J. Chen, and D. Gaylor, 1991, Risk Anal. 11, 583-590). Generalizations of those models (designated the RVR, LOG, and NCTR models, respectively) account for the correlations among observations in individual fetuses or implant within litters; the potential for variables other than dose, such as litter size, to affect the probability of adverse outcome; and the possibility of a threshold dose below which background response rates are unaltered. The generalized models were applied to a database of 607 endpoints with significant dose-related increases in response rate. It was determined that the models were generally capable of fitting the observed dose-response patterns, with the LOG model appearing to be superior with respect to fit. A significant contributor to the ability of the LOG model to fit the data was its flexibility with respect to the representation of the dependence of response probability on litter size, a trait not shared by the other two models. Litter size appeared to be a significant covariable for predicting response rates, even when intralitter correlation was accounted for by assuming a beta-binomial distribution for the observations among individual fetuses. In contrast, a threshold dose parameter did not appear to be necessary to adequately describe the observed dose-response patterns. BMD estimates (corresponding to 5% additional risk) from all three models were similar to one another and to BMDs estimated from other, generic dose response models (not specifically designed for developmental toxicity testing) that modeled average proportion of fetuses affected. The BMDs at the 5% level of risk were similar to no observed adverse effect levels determined by statistical tests of trend. Greater emphasis on and further examination of dose-response modeling for developmental toxicity testing are needed; biologically based approaches that consider the continuum of developmental effects induced in such tests should be encouraged. PMID- 7867902 TI - Olfactory mucosal lesions in F344 rats following inhalation exposure to pyridine at threshold limit value concentrations. AB - Pyridine is a volatile solvent used as an intermediate in the production of insecticides, herbicides, pharmaceuticals, and dyes. Pyridine is also found in tobacco smoke. Because inhalation is a primary route of exposure to pyridine, we examined the effect of inhaled pyridine on morphology at the portal of entry, the nose. Nasal tissues from F344/N rats exposed using a nose-only mode 6 hr/day for 4 days to either filtered air (controls) or one of two concentrations of pyridine vapor were examined histologically. The rats had been killed 18 hr after the last exposure. The two pyridine concentrations were the current threshold limit value (TLV, 5 ppm) and a high concentration (444 ppm). Olfactory epithelial lesions in rats exposed to both concentrations of pyridine included vacuolar degeneration of sustentacular cells; focal, marked attenuation of the epithelium; loss of vacuolar degeneration of sustentacular cells; focal, marked attenuation of the epithelium; loss of neurons; and the presence of intraepithelial luminal structures. The lesions were only slightly more severe in the rats exposed to 444 ppm compared to those rats exposed to 5 ppm pyridine. The results show that inhalation of pyridine at the current TLV concentration of 5 or 444 ppm causes lesions in the olfactory epithelium of rats. PMID- 7867903 TI - Chronic effects of dietary fumonisin on the heart and pulmonary vasculature of swine. AB - Fumonisins, mycotoxins produced in Fusarium moniliforme-infected corn, are hepatotoxic in several species and induce hepatocarcinomas in laboratory rats, leukoencephalomalacia in equine species, and fulminant pulmonary edema in swine. To date, the effects of fumonisin on pigs has dealt solely with the high levels required to induce the dramatic development of acute fulminant, and usually lethal, pulmonary edema. Less sensational, but equally important, are the chronic effects of fumonisin on swine health. In the first trial, six gilts were fed, ad libitum, a formulated complete ration containing 100 mg fumonisin B1 (FB1)/kg for 10 days followed by a ration containing 190 mg FB1/kg for up to 83 days. In the second trial, five gilts were fed, ad libitum, rations containing 150-170 mg FB1/kg for up to 210 days. The concentration of fumonisin B2 (FB2) was 31 +/- 2% that of the FB1. Weight-matched controls were selected for cardiac parameter comparison. Pigs fed fumonisin for at least 93 days developed nodular hyperplasia of the liver. Evidence from the microscopic examination of heart and lungs and gravimetric measurements of cardiac tissues from four pigs exposed to dietary fumonisins for 6 months suggests that the pulmonary vasculature is a target of chronic exposure. This study provides additional evidence linking the pathogenesis of fumonisin-induced lesions in a variety of organ systems of various animal species to a vascular mechanism. PMID- 7867904 TI - DNA-protein cross-links and cell replication at specific sites in the nose of F344 rats exposed subchronically to formaldehyde. AB - Chronic exposures to high concentrations (> or = 6 ppm) of formaldehyde (HCHO) induce cell proliferation, squamous metaplasia, and squamous cell carcinomas in F344 rats. To assess the cancer risk associated with HCHO exposure, DNA-protein cross-links (DPX) formed in a single exposure of naive (previously unexposed) rats and monkeys have been used as a surrogate for the internal dose. Since the quantity of DPX may differ in subchronically exposed animals, the effects of preexposure to HCHO on the acute DPX yield (concentration of DPX following a single exposure) and the cumulative DPX yield (concentration of DPX following repeated exposures) were determined. Male F344 rats were preexposed (PE) to 0.7, 2, 6, or 15 ppm of HCHO (6 hr/day, 5 days/week, 11 weeks + 4 days). Naive (N) rats were exposed to room air. On the 5th day of the 12th week, PE and N rats were simultaneously exposed (3 hr) to H14CHO at the same concentrations used for preexposure. Acute DPX yields and cell replication (incorporation of 14C into DNA) were determined in the mucosal lining of the nasal lateral meatus (LM) (high tumor site in HCHO bioassay) and the medial and posterior meatuses (M:PM) (low tumor site in bioassay). DPX yields in the LM were approximately sixfold higher than in the M:PM. At 0.7 and 2 ppm, no differences between PE and N rats were detected in either tissue. At 6 and 15 ppm, acute DPX yields in the LM of PE rats were approximately half those of N rats, but no differences were detected in the M:PM. Cell proliferation was induced in PE rats at 6 ppm (LM only) and especially at 15 ppm (LM and M:PM). Cumulative DPX yields were measured indirectly by determining the decrease in extractability of DNA from proteins. PE rats were preexposed to 6 or 10 ppm as above, while N rats were exposed to room air. Both groups (PE and N) were then exposed (3 hr) to the same concentration of unlabeled HCHO. DPX yields increased in a concentration-dependent manner in both groups, but the yields were smaller in PE than N rats, suggesting that no accumulation of DPX occurred in PE rats. The results demonstrate that at concentrations < or = 2 ppm, N and PE rats are equivalent with respect to the formation of DPX.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7867905 TI - Induced cytolethality and regenerative cell proliferation in the livers and kidneys of male B6C3F1 mice given chloroform by gavage. AB - It has been reported that chloroform administered to male B6C3F1 mice at doses of 138 and 277 mg/kg/day in corn oil by gavage 5 days/week for 2 years resulted in incidences of hepatocellular carcinomas of 36 and 98% relative to an incidence in controls of 6%. Cytotoxicity and regenerative cell proliferation have been implicated in the tumorigenic process for this non-genotoxic compound. Although chloroform is known to be nephrotoxic in the male mouse, no treatment-related increase was observed in the frequency of kidney tumors. To better understand the relationship of these endpoints, this study evaluated chloroform-induced cytotoxicity and cell proliferation in the liver and kidney under conditions of the cancer study. B6C3F1 mice were administered oral doses of 0, 34, 90, 138, or 277 mg/kg/day of chloroform dissolved in corn oil for 4 days or 5 days/week for 3 weeks. Bromo-2'-deoxyuridine (BrdU) was administered via osmotic pumps implanted 3.5 days prior to necropsy to label cells in S-phase. Cell proliferation was evaluated in tissue sections immunohistochemically as the percentage of cells in S-phase (nuclear labeling index; LI). Mice given 34 and 90 mg/kg/day by gavage had mild degenerative changes in centrilobular hepatocytes after 4 days of treatment, which was absent at 3 weeks. Centrilobular necrosis was observed in mice given 138 or 277 mg/kg chloroform for 4 days, with increased severity of necrosis at 3 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867906 TI - Comparison of renal toxicity after long-term oral administration of cadmium chloride and cadmium-metallothionein in rats. AB - There is a clear lack of information on the toxicological risk of dietary intake of cadmium-metallothionein (CdMt). The present study aimed at establishing dose dependent cadmium (Cd) disposition and to investigate differences in renal toxicity after long-term dietary exposure to CdMt or cadmium chloride (CdCl2) in rats. Male Wistar rats were fed diets containing 0.3, 3, 30, or 90 mg Cd/kg either as CdMt or as CdCl2 for 10 months. In rats fed 30 and 90 mg/kg Cd as CdCl2 the Cd concentrations in intestine, liver, and kidneys were all higher than in rats fed the same doses in the form of CdMt. The kidney/liver Cd concentration ratio was higher with CdMt than with CdCl2. At the lower Cd concentrations (0.3 and 3 mg/kg), no differences in Cd accumulation between CdMt and CdCl2 groups were observed and the kidney/liver Cd ratio was also similar. When based on the amount of CdMt per milligram Cd in the tissue, rats fed CdMt and those fed CdCl2 had a similar relative CdMt concentration in liver and kidney. First signs of renal injury, indicated by an increase of urinary lactate dehydrogenase (LDH) activity, were seen 4 months after exposure to 90 mg/kg Cd as CdCl2. After 8 and 10 months the renal effect of 90 mg/kg Cd as CdCl2 became more pronounced and urinary enzyme activities of LDH, N-acetyl-beta-D-glucosaminidase and alkaline phosphatase were all elevated. The only clinical effect of CdMt at the dose level of 90 mg/kg was a slight increase in urinary gamma-glutamyl transpeptidase activity at 8 and 10 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867907 TI - Behavioral impairments of lead-injected young herring gulls in nature. AB - Lead is ubiquitous in the environment, and trace amounts enter the food chain and bioaccumulate in organisms high on the food chain. Although lead levels have been examined in a variety of wild species, effects data are usually from laboratory studies. Thus the relevance of effects to survival and fitness are not directly determined. In the field we compared the behavior of lead-injected young herring gulls (Larus argentatus) to the behavior of their control siblings who received an injection with no lead and to chicks from control nests that received no injections. Lead-injected chicks had significantly lower survival rates than all controls. Lead-injected chicks were less healthy than control chicks as measured by begging and walking scores and by the number of times they stumbled when walking. Control chicks had a higher degree of accuracy when pecking at their parents' bills to stimulate feeding compared to the lead-injected chicks. For all chicks, begging and walking scores improved with age. Behavioral deficits measured in the laboratory are homologous with those observed in the field. PMID- 7867908 TI - Evaluation of an azo and two anthraquinone dyes for allergic potential. AB - Two dye mixtures and the individual component dyes were evaluated for the potential to induce contact or pulmonary hypersensitivity. These dye mixtures were suspect because of anecdotal reports of both pulmonary and contact hypersensitivity in assembly workers, and because the component dyes were structurally related to dyes known to be contact sensitizers. One mixture consisted of disperse blue 3 (DB3) and disperse red 11 (DR11), which are anthraquinones, and the other mixture contained DR11 and solvent red 1 (SR1), an azo dye. Contact hypersensitivity was examined using the local lymph node assay (LLNA) and a modified mouse ear swelling test (MEST). Both the MEST and the LLNA indicated that SR1 has weak contact-sensitizing potential. None of the other individual dye compounds or the two mixtures were identified as contact sensitizers by either method. To evaluate the mixtures as potential pulmonary allergens, guinea pigs were repeatedly exposed by inhalation (300 mg/m3, 6 hr/day) 5 days/week, for 1 week. Weekly exposures were repeated three times with 2 weeks of nonexposure time in between. Guinea pigs were then challenged through the jugular vein using a dye-dimethylsulfoxide mixture. During the challenge, breathing mechanics (dynamic compliance and resistance) were measured in mechanically ventilated animals. Changes in these measurements, indicative of bronchoconstriction, were not observed in animals exposed to either dye mixture, nor were antibodies detected in the sera of exposed animals using individual dye specific enzyme-linked immunosorbent assays. In conclusion, two methods indicate that SR1 may have contact-sensitizing potential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867909 TI - Phosphotriesterase--a promising candidate for use in detoxification of organophosphates. AB - The effect of phosphotriesterase (PTE) on cholinesterase (ChE) activities was studied with exposures to different organophosphates in mice. Paraoxon (PO) (1.0 mg/kg, ip) almost totally inhibited serum ChE activity. This activity, however, recovered to the normal level within 24 hr. The PTE pretreatment (16.8 U/animal, 2.5 micrograms/10 g body wt, iv 10 min before the organophosphate) accelerated this reactivation. The same phenomenon was also seen in vitro. In vitro with human serum, there was only minimal reactivation of the inhibited ChE. PTE, however, reactivated it significantly. The PTE-pretreated mice (168 U/animal, 30 micrograms/10 g body wt, iv) tolerated even 50 mg/kg of PO without showing any remarkable signs of intoxication. In PTE-untreated animals, however, PO doses as low as 1.0 and 1.5 mg/kg caused severe signs of poisoning. PTE (16.8 U/animal, 4 micrograms/10 g body wt, iv) reduced the inhibition of brain and serum ChE activities after PO and diisopropyl fluorophosphate exposure. In sarin and soman intoxications, PTE decreased only slightly the inhibition of ChE activities. The results indicate that PTE pretreatment given iv prevents the inhibition of ChE activities after certain organophosphates and it also hastens the recovery of activities after PO poisoning. PMID- 7867910 TI - Developmental toxicity studies in mice, rats, and rabbits with the anticonvulsant gabapentin. AB - The developmental toxicity of the anticonvulsant agent gabapentin was evaluated in mice, rats, and rabbits treated by gavage throughout organogenesis. Mice received 500, 1000, or 3000 mg/kg on gestation days (GD) 6-15 and rats and rabbits received 60, 300, or 1500 mg/kg on GD 6-15 (rats) or 6-18 (rabbits). Additional groups received an equivalent volume of the vehicle, 0.8% methylcellulose, or remained untreated. All dams were observed daily for clinical signs of toxicity. In mice, body weights and food consumption were recorded on GD 0, 6, 12, 15, and 18 while in rats and rabbits these parameters were evaluated daily. Near term (mouse, GD 18; rat, GD 20; and rabbit, GD 29) each female was euthanatized, necropsies were performed, and litter and fetal data were collected. Live fetuses were examined for external, visceral, and skeletal variations and malformations. No adverse maternal or fetal effects were observed in mice or rats given doses up to 1500 or 3000 mg/kg, respectively. No treatment related maternal or fetal effects were apparent in rabbits given 60 or 300 mg/kg. At 1500 mg/kg, one rabbit died, four others aborted, and reduced food consumption and body weight gain were observed. No other reproductive, litter, or fetal parameters were affected, except that the incidence of visceral variations in rat fetuses was slightly but statistically significantly increased at 1500 mg/kg due to a slight increase in the incidence of dilated renal pelvis. This finding was not considered biologically significant because this degree of variability has been seen in this strain of rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7867911 TI - Developmental toxicology studies of vancomycin hydrochloride administered intravenously to rats and rabbits. AB - Pregnant CD rats were given vancomycin intravenously in doses of 0, 40, 120, or 200 mg/kg on Gestation Days (GD) 6-15; pregnant New Zealand white rabbits were given 0, 40, 80, or 120 mg/kg intravenously on GD 6-18. Cesarean sections were performed on rats and rabbits on GD 20 and 28, respectively. In rats, maternal toxicity was indicated in the 120- and 200-mg/kg treatment groups by cortical tubular nephrosis. Maternal body weight gain and food consumption and fetal viability, weight, and morphology were not adversely affected by vancomycin. Maternal and developmental no observed adverse effect levels (NOAELs) in the rat were 40 and 200 mg/kg, respectively. In rabbits, maternal toxicity was indicated by cortical tubular nephrosis in the 80- and 120-mg/kg treatment groups; a single death and depression of body weight gain and food consumption occurred in the 120 mg/kg treatment group. Developmental toxicity was indicated by depression of fetal weight in the 120-mg/kg treatment group; fetal viability and morphology were not adversely affected by vancomycin. Maternal and developmental NOAELs in the rabbit were 40 and 80 mg/kg, respectively. Based on these data, vancomycin did not exhibit selective toxicity toward the developing rat or rabbit conceptus. PMID- 7867913 TI - Prenatal toxicity of inhalation exposure to 2-methoxypropanol-1 in rabbits. AB - 2-Methoxypropanol-1 was investigated for prenatal toxicity in Himalayan rabbits after inhalation exposure to 0, 145, 225, 350, and 545 ppm for 6 hr per day from Gestation Day 6 through 18. Maternally toxic effects were found with decreased body weights from Day 12 of gestation through the end of the study at 545 ppm. A dose-dependent increase of resorptions, fetal malformations, and variations was observed at 225, 350, and 545 ppm, whereas 145 ppm was devoid of exposure-related effects. The malformation rate at 545 ppm was 100%. The types of malformations mainly consisted of absent phalanges and absent or rudimentary metatarsal bones, malformed ribs, and a unique enlargement of sternebrae. The effects are very similar to those previously found with 2-methoxypropyl-acetate-1. The results of this study may have implications for the quantitative estimation of risks associated with 2-methoxy-propanol-1 impurities in the widely used isomer 1 methoxypropanol-2 which itself does not show developmental toxicity. PMID- 7867912 TI - Relative sensitivities of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced Cyp1a-1 and Cyp1a-2 gene expression and immunotoxicity in female B6C3F1 mice. AB - Improvements in risk assessment require better linkage of exposure to response by the determination of target tissue dose. The relative sensitivity of several responses in female B6C3F1 mice was compared on the basis of administered and target tissue dose spanning 3 orders of magnitude. Twenty-four hours after administration, [3H]TCDD was detected in the heart, spleen, kidney, uterus, thymus, lung, and liver, and the highest concentrations were noted in the liver, uterus, and lung. At doses from 5 to 25 ng/kg, hepatic [3H]TCDD levels associated with the cytosolic and nuclear subcellular fractions increased from 12 to 62% of the total liver levels and then decreased at higher doses. At the two lowest doses used in the enzyme induction study, 5 and 10 ng/kg, the levels of specifically bound nuclear Ah receptor complex liganded with [3H]TCDD were 2.3 and 2.5 fmol/mg protein. Slightly higher levels of nuclear Ah receptor complex were observed at doses between 25 and 100 ng/kg (i.e., 3.6 to 4.2 fmol/mg protein) and a steep dose-dependent increase in nuclear Ah receptor levels was noted at doses of 500, 1000, and 5000 ng/kg (8.0, 39.3, and 92.8 fmol/mg protein, respectively). The dose-dependent effects of [3H]TCDD on hepatic Cyp1a-1 and Cyp1a-2 mRNA levels, ethoxyresorufin O-deethylase (EROD) activity, and the splenic antibody plaque-forming cell (PFC) response to sheep red blood cells were also determined; the latter response was determined 9 days after administration of TCDD. Statistically significant induction of hepatic Cyp1a-1 was observed at lower doses (25 ng/kg) than any other marker, followed by induction of EROD and PFCs expressed per spleen or per 10(6) cells which was observed at 100 ng TCDD/kg and at higher doses. Cyp1a-2 was elevated significantly relative to control at doses > or = 1000 ng/kg. The ED50 value for PFCs/10(6) cells was the lowest of the variables analyzed and was not statistically significantly different from control (91 +/- 92 ng/kg). A 50% increase in Cyp1a-2 and Cyp1a-1 mRNA levels was observed at doses of 736 +/- 132 and 1630 +/- 431 ng/kg, respectively. Due to variability in response in PFCs/spleen and the submaximal induction of EROD activity, ED50 values could not be calculated for these responses. The analyses indicate that the immunosuppressive response (when normalized for the number of spleen cells) may be depressed by administered doses as low as 90 ng TCDD/kg body weight. A 50% increase in Cyp1a-1 or Cyp1a-2 was observed at higher administered doses (1630 or 736 ng/kg, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7867914 TI - A 26-kDa outer membrane protein, OmpK, common to Vibrio species is the receptor for a broad-host-range vibriophage, KVP40. AB - KVP40 is a broad-host-range vibriophage forming plaques on strains of at least eight Vibrio and one Photobacterium species. A spontaneous KVP40-resistant mutant, R4000, derived from Vibrio parahaemolyticus 1010 lacked a 26-kDa outer membrane protein designated OmpK. KVP40 was inactivated by outer membrane and OmpK prepared from 1010, but not by outer membrane from R4000. These results strongly suggest that OmpK is the receptor for KVP40. Immunoblotting analyses using an anti-OmpK rabbit serum revealed that OmpK or its homologs of molecular masses 25-29 kDa were distributed widely among Vibrio and Photobacterium strains including those naturally resistant to KVP40. PMID- 7867915 TI - A new method for integration and stable DNA amplification in poorly transformable bacilli. AB - We have developed a strategy for the integration and stable amplification of DNA sequences in the chromosome of poorly transformable bacilli, which avoids the presence of a functional plasmid replication system in the integrated DNA. The parental vector for integration contains two plus origins of replication from pUB110 in the same orientation on a single plasmid. Due to the direct repeats, such plasmids produce two individual progeny vectors, one of which is dependent on the other for replication, as it lacks a functional rep gene. We have used such a progeny vector system to integrate and amplify DNA on the chromosome of Bacillus licheniformis, and show that the structure is stable in the absence of selective pressure. PMID- 7867916 TI - Cellulases and hemicellulases of the anaerobic fungus Piromyces constitute a multiprotein cellulose-binding complex and are encoded by multigene families. AB - More than 80% of the extracellular Avicelase, endoglucanase, xylanase and mannanase activities of the anaerobic fungus Piromyces were associated with a cellulose-binding complex. The complex was composed of at least 10 polypeptides ranging in size from 190 kDa to 50 kDa, and contained numerous endoglucanases, xylanases and mannanases. Multiple genes encoding each of these activities were isolated from an expressing cDNA library. PMID- 7867917 TI - Modular structure of genes encoding multifunctional peptide synthetases required for non-ribosomal peptide synthesis. AB - Peptide synthetases are large multienzyme complexes that catalyze the non ribosomal synthesis of a structurally diverse family of bioactive peptides. They possess a multidomain structure and employ the thiotemplate mechanism to activate, modify and link together by amide or ester bonds the constituent amino acids of the peptide product. The domains, which represent the functional building units of peptide synthetases, appear to act as independent enzymes whose specific linkage order forms the protein-template that defines the sequence of the incorporated amino acids. Two types of domains have been characterized in peptide synthetases of bacterial and fungal origin: type I comprises about 600 amino acids and contains at least two modules involved in substrate recognition, adenylation and thioester formation, whereas type II domains carry in addition an insertion of about 430 amino acids that may function as a N-methyltransferase module. The role of other genes associated with bacterial operons encoding peptide synthetases is also discussed. PMID- 7867918 TI - o-, m- and p-hydroxybenzoate degradative pathways in Rhodococcus erythropolis. AB - Rhodococcus erythropolis strain S1 uses the gentisate pathway to metabolize salicylate and m-hydroxybenzoate and the protocatechuate pathway to degrade p hydroxybenzoate. m-Hydroxybenzoate 6-hydroxylase was induced by growth on m hydroxybenzoate or gentisate, and salicylate 5-hydroxylase only by growth on salicylate. p-Hydroxybenzoate 3-hydroxylase could be induced only by growth on p hydroxybenzoate. m-Hydroxybenzoate or p-hydroxybenzoate could repress the induction of salicylate 5-hydroxylase. Maleylpyruvate isomerase in the gentisate pathway did not require reduced glutathione. PMID- 7867919 TI - Functional expression in Saccharomyces cerevisiae of the Lactococcus lactis mleS gene encoding the malolactic enzyme. AB - Malolactic fermentation, a crucial step in winemaking, results mostly in degradation by lactic acid bacteria of L-malic acid into L-lactic acid. This direct decarboxylation is catalysed by the malolactic enzyme. Recently we, and others, have cloned the mleS gene of Lactococcus lactis encoding malolactic enzyme. Heterologous expression of mleS in Saccharomyces cerevisiae was tested to perform simultaneously alcoholic and malolactic fermentations by yeast. mleS gene was cloned in a yeast multicopy vector under a strong promoter. Malolactic activity was present in crude extracts of recombinant yeasts. Malic acid degradation was tested during alcoholic fermentation in synthetic media and must. Yeasts expressing the mleS gene actually produced L-lactate from L-malate; nevertheless malate degradation was far from complete. PMID- 7867920 TI - Double-stranded RNA mycoviruses in mycelium of Pleurotus ostreatus. AB - Mycelium of Pleurotus ostreatus var. florida with a decreased growth rate contained seven double-stranded RNA segments and isometrical virus particles with diameters of 24 and 30 nm. Mycelium with a normal growth rate lacked dsRNA. Protoclones from virus-containing mycelium contained one to seven of these dsRNA segments in varying concentrations. The exact correlation between slow growth and the presence of dsRNA molecules could not be established. Infection of virus-free protoplasts with PEG-precipitated virus particles resulted in mycelium that stably maintained the 2.4 kbp dsRNA. PMID- 7867921 TI - Image analysis of lysosomal activity during the early clonal life of Paramecium primaurelia. AB - Acid phosphatase activity was measured in individual cells by determining their optical densities through a scanning confocal laser microscope. The naphthol AS TR (3-hydroxy-2-naphtoic acid 4'-chloro-2'-methylanilide) phosphate-hexazotized para-rosanilin method was used to visualise the acid phosphatase content in the light microscope. Evidence was obtained that the amount of enzyme varied in exponential growth phase cells as the fission age increased. By comparing the acid phosphatase activity with the rate of food vacuole formation, it appeared that the amount of enzyme inside the cells decreased in early clonal life, whereas the rate of food uptake increased. It was assumed that the reduction of acid phosphatase content could lead to a more extended life of vacuoles and to a decreased membrane recycling rate. In turn, the reduced supply of membrane available for food vacuole formation could partly be responsible for the decrease of the food uptake rate observed after the initial increase. PMID- 7867922 TI - DNA from Serratia marcescens confers a hydrophobic character in Escherichia coli. AB - In order to determine whether hydrophobic surface properties of Serratia marcescens can be transferred to Escherichia coli, E. coli DH5 alpha cells were transformed by DNA fragments from S. marcescens RZ. Fifteen-hundred E. coli transformants were screened for adhesion to hexadecane and polystyrene. One transformant exhibited increased adhesion to hexadecane droplets, as well as altered kinetics of aggregation in the presence of ammonium sulfate. Western colony blotting revealed that antibodies raised against S. marcescens RZ recognized component(s) on the transformant outer surface. PMID- 7867923 TI - Isolation and characterization of a new hydrogen-utilizing bacterium from the rumen. AB - A new H2/CO2-utilizing acetogenic bacterium was isolated from the rumen of a mature deer. This is the first report of a spore-forming Gram-negative bacterial species from the rumen. The organism was a strictly anaerobic, motile rod and was able to grow autotrophically on hydrogen and carbon dioxide. Acetate was the major product detected. Glucose, fructose and lactate were also fermented heterotrophically. The optimum pH for growth was 7.0-7.5, and the optimum temperature was 37-42 degrees C. Yeast extract was required for growth and rumen fluid was highly stimulatory. The DNA base ratio was 52.9 +/- 0.5 mol% G+C. On the basis of these characteristics and fermentation products, the isolate was considered to be different from acetogenic bacteria described previously. PMID- 7867924 TI - Kinetics of cobalamin repression of the cob operon in Salmonella typhimurium. AB - The cob operon in Salmonella typhimurium encodes 25 proteins involved in the biosynthesis of cobalamin. Expression of the cob operon is negatively feedback regulated by cobalamin via a translational control mechanism. The concentration of cobalamin required to repress cob expression to half-maximal was determined in vivo and in vitro to 0.4 microM and 0.6 microM, respectively. These results suggest that cob expression in wild-type cells is partially repressed by de novo synthesized cobalamin. PMID- 7867925 TI - Variability of peptidoglycan structural parameters in gram-negative bacteria. AB - Muropeptide composition of peptidoglycan from the Gram-negative bacteria Aeromonas sp., Acinetobacter acetoaceticus, Agrobacterium tumefaciens, Enterobacter cloacae, Proteus morganii, Pseudomonas aeruginosa, Pseudomonas putida, Vibrio parahaemolyticus Yersinia enterocolitica and Escherichia coli, was analyzed by HPLC. In all instances peptidoglycan was built up from the same subunits. A wide disparity in the relative abundance of muropeptides and all structural parameters was observed. The contribution of LD-A2pm-A2pm cross-linked muropeptides was extremely variable; from 1 to 45% of cross-linked muropeptides. Muropeptides with the dipeptides Lys-Lys or Arg-Lys, indicative of murein-bound (lipo)proteins, were detected in all instances although abundance was very variable. PMID- 7867926 TI - Soma-specific expression and cloning of PSI, a negative regulator of P element pre-mRNA splicing. AB - PSI is an RNA-binding protein involved in repressing splicing of the P element third intron in Drosophila somatic cell extracts. PSI produced in bacteria restores splicing inhibition to an extract relieved of inhibitory activity, indicating that PSI plays a direct role in somatic inhibition. Sequence analysis of cDNAs encoding PSI reveals three KH RNA-binding domains, a conserved motif also found in the yeast splicing regulator MER1. Notably, PSI is expressed highly in somatic embryonic nuclei but is undetectable in germ-line cells. In contrast, hrp48, another protein implicated in somatic inhibition, is found in the nucleus and cytoplasm of both tissues. The splicing inhibitory properties and soma specific expression of PSI may be sufficient to explain the germ-line-specific transposition of P elements. PMID- 7867927 TI - Synergistic interactions between two distinct elements of a regulated splicing enhancer. AB - Regulated alternative splicing of doublesex (dsx) pre-mRNA requires a splicing enhancer designated the dsx repeat element (dsxRE) that contains six copies of a 13-nucleotide repeat sequence. Previous studies have shown that the activity of the dsxRE requires the splicing regulators Transformer (Tra) and Transformer 2 (Tra2), and one or more members of the SR family of general splicing factors. In this paper we identify a purine-rich enhancer (PRE) sequence within the dsxRE, and show that this element functionally synergizes with the repeat sequences. In vitro binding studies show that the PRE is required for specific binding of Tra2 to the dsxRE, and that Tra and SR proteins bind cooperatively to the dsxRE in the presence or absence of the PRE. Thus positive control of dsx pre-mRNA splicing requires the Tra- and Tra2-dependent assembly of a multiprotein complex on at least two distinct enhancer elements. PMID- 7867928 TI - Regulation of human RPS14 transcription by intronic antisense RNAs and ribosomal protein S14. AB - RNase protection studies reveal two stable RNAs (250 and 280 nucleotides) transcribed from the antisense strand of the human ribosomal protein gene RPS14's first intron. These transcripts, designated alpha-250 and alpha-280, map to overlapping segments of the intron's 5' sequence. Neither RNA encodes a polypeptide sequence, and both are expressed in all human cells and tissues examined. Although alpha-280 is detected among both the cells' nuclear and cytoplasmic RNAs, the great majority of alpha-250 is found in the cytoplasmic subcellular compartment. As judged by its resistance to high concentrations of alpha-amanitin, cell-free transcription of alpha-250 and alpha-280 appears to involve RNA polymerase I. Tissue culture transfection and cell-free transcription experiments demonstrate that alpha-250 and alpha-280 stimulate S14 mRNA transcription, whereas free ribosomal protein S14 inhibits it. Electrophoretic mobility shift experiments indicate specific binary molecular interactions between r-protein S14, its message and the antisense RNAs. In light of these data, we propose a model for fine regulation of human RPS14 transcription that involves RPS14 intron 1 antisense RNAs as positive effectors and S14 protein as a negative effector. PMID- 7867929 TI - Targeting expression of a dominant-negative retinoic acid receptor mutant in the epidermis of transgenic mice results in loss of barrier function. AB - To study the effects of retinoic acid on the skin in vivo, we have subverted the activity of endogenous receptors by targeting expression of a dominant negative mutant of retinoic acid receptor alpha (RAR alpha) to the epidermis of transgenic mice. At birth, mice expressing the mutant RAR alpha transgene exhibited a marked phenotype of a red, shiny skin that was somewhat sticky to touch. Severely affected neonates died within 24 hr. Histological changes in the epidermis were subtle with the phenotypic stratum corneum appearing slightly thinner and more loosely packed than in controls. Electron microscopic studies revealed that lipid multilamellar structures were not present between cells in the stratum corneum of phenotypic mice. When assayed for transepidermal water loss, phenotypic skin lost water at a rate three times faster than controls, suggesting that neonatal lethality resulted from loss of epidermal barrier function. The absence of a functional lipid barrier in transgenic mice first became evident at E17 when lipids were extruded initially into the intercellular space. We have identified a potential pathway linking inhibition of retinoid signaling with disruption of the lipid barrier that involves peroxisome proliferator-activated receptors. This study documents the role of the retinoid signaling pathway in formation and maintenance of a functional epidermis and provides the first evidence that this is mediated in part by modulation of lipid metabolism. PMID- 7867930 TI - The SABRE gene is required for normal cell expansion in Arabidopsis. AB - Regulated cell expansion is an important determinant of organ shape in higher plants. The sabre mutation results in abnormal cell expansion in Arabidopsis. There is a shift in the orientation of expansion evident primarily in root cortex cells. The SABRE gene has been cloned and found to encode a novel protein. Reduction of effective levels of the plant phytohormone ethylene through use of inhibitors and an insensitive mutant resulted in partial rescue of the sabre phenotype. This suggested that one of the roles of SABRE is to counter the action of ethylene in promoting radial expansion in plant cells. PMID- 7867931 TI - lin-25, a gene required for vulval induction in Caenorhabditis elegans. AB - During vulval development in the Caenorhabditis elegans hermaphrodite, the fates of six vulval precursor cells (VPCs) are influenced by distinct cell signaling events. In one event, a somatic gonadal cell, the anchor cell, induces the three nearest VPCs to adopt vulval cell fates. In another event, lateral signaling between adjacent VPCs specifies one of two different vulval fates, 1 degrees and 2 degrees. Induction of vulval fates by the anchor cell is mediated by a signal transduction pathway involving let-60 Ras, lin-45 Raf, and mpk-1/sur-1 MAP kinase, whereas lateral signaling is mediated by lin-12. We have shown that the mutant phenotype of lin-25, a gene required for VPC fate specification, results from a defect in vulval induction. Genetic epistasis experiments indicate that lin-25 is required in the inductive signaling pathway downstream of let-60 Ras and the Raf/MAP kinase cascade. A decrease in induction also appears to decrease lateral signaling. We have cloned and sequenced the lin-25 gene and shown that it encodes a novel protein that may be a target of the mpk-1/sur-1 MAPK. PMID- 7867933 TI - Action of a RAP1 carboxy-terminal silencing domain reveals an underlying competition between HMR and telomeres in yeast. AB - RAP1 is a sequence-specific DNA-binding protein in yeast that can either repress or activate transcription. Previous studies have demonstrated a direct role for RAP1 in silencing at HM mating-type loci and telomeres. Here, we show that a small carboxy-terminal domain of RAP1 is sufficient to establish repression when fused to the GAL4 DNA-binding domain (GBD) and targeted to mutated HMR silencers containing GAL4 DNA-binding sites. Silencing by GBD/RAP1 hybrids, like normal silencing at HMR, requires the trans-acting factors SIR2, SIR3, and SIR4. However, GBD/RAP1-mediated silencing is independent of SIR1, whose product is normally required for the establishment of repression at HMR. Targeted silencing also displays an unusual response to silencing-defective rap1s mutations. The incorporation of a rap1s missense mutation into GBD/RAP1 hybrids can improve targeted silencing, yet wild-type GBD/RAP1 hybrids fail to establish repression in strains in which the endogenous RAP1 locus carries a rap1s mutation. In addition, we find that telomeric silencing is increased in rap1s strains. We propose that the rap1s mutation creates an HMR-specific silencing defect by shifting a balance between silencing at HMR and telomeres in favor of telomeric silencing. This balance is regulated by telomere length and by interactions between the RAP1 carboxyl terminus and both RIF1 and SIR4 proteins. In support of this model, we show that abnormally long telomeres antagonize silencing at HMR and a rap1s hybrid protein displays a strengthened interaction with SIR4 in a two hybrid assay. PMID- 7867932 TI - Regulation of dorsal in cultured cells by Toll and tube: tube function involves a novel mechanism. AB - We described previously a transient cotransfection assay that allows us to study regulation of the Drosophila Dorsal protein (dl) in cultured cells. For example, we showed that over-expression of the Toll transmembrane receptor was sufficient to cause relocalization of dl from the cytoplasm to the nucleus. Here we present data that the tube protein, shown previously by genetic studies to act downstream of Toll, can function in a novel way to enhance dl activity. In the absence of dl, or when dl is cytoplasmic, tube is also found in the cytoplasm of transfected cells. But when dl is localized to the nucleus, so is tube. tube can then function to enhance reporter gene expression, either by cooperation with dl or as a GAL4-tube fusion protein. tube thus appears capable of acting both as a chaperon or escort for dl as it moves to the nucleus, and then as a transcriptional coactivator. We also show that the intracytoplasmic domain of Toll, and specifically the region sharing homology with the interleukin-1 receptor, is sufficient to induce dl-tube nuclear translocation. PMID- 7867934 TI - Characterization of an insertion in the phage phi 105 genome that blocks host Bacillus subtilis lysis and provides strong expression of heterologous genes. AB - A defective prophage vector, phi 105MU331, for high-level protein overproduction in Bacillus subtilis, was derived by random insertion of a lacZ reporter gene. The site of insertion not only provided efficient inducible transcription of heterologous genes, but also prevented lysis of the host cell. The region of the insertion in phi 105MU331 lies close to the right cohesive end of phi 105. DNA sequence analysis revealed that this region of phi 105 somewhat resembles the lysis cassette of various phages, including lambda. The site of insertion lies in a possible 'holin' gene, which could explain the block in host cell lysis. Dual promoters apparently responsible for the strong inducible transcription lie in an untranslated region just upstream from the putative holin gene. This region is probably equivalent to the site of the major late promoter and antiterminator of the lambdoid phages. The sequence features could, thus, account for the useful properties of the phi 105MU331 vector system. PMID- 7867935 TI - Vectors with the gus reporter gene for identifying and quantitating promoter regions in Saccharomyces cerevisiae. AB - The Escherichia coli beta-glucuronidase-encoding gene gusA is useful as a reporter gene in a variety of organisms. In this report, we describe the development of two related vectors, pGUS1 and pGUS2, which can be used to identify and quantitate activities of the promoter regions from yeast genes. Both vectors contain several unique restriction sites upstream from gus and the yeast CYC1 transcription terminator downstream from gus. In addition, pGUS2 carries the yeast ADH1 transcriptional terminator sequence upstream from gus, in order to block read-through transcription originating in vector sequences. Both vectors were tested after cloning the well-characterized GAL1,10 promoter region from yeast. These GAL1,10-containing plasmids demonstrated appropriate regulation of the reporter in response to carbon sources. The pGUS1 and pGUS2 vectors provide a simple, reliable and extremely sensitive reporter-gene system that allows quantitative measurement of promoter activity of yeast DNA sequences. Furthermore, the presence of a terminator sequence upstream from gus in pGUS2 should facilitate analysis and quantitation of expression from weak promoters. PMID- 7867936 TI - A cDNA from Schizosaccharomyces pombe encoding a putative enolase. AB - Here we report the isolation of an enolase (Eno)-encoding cDNA clone from Schizosaccharomyces pombe. The deduced amino acid (aa) sequence of the 1.4-kb cDNA shares identifies with a number of Eno from Escherichia coli to humans. The highest degree of similarity is to the known Eno from Saccharomyces cerevisiae and an Eno from Candida albicans. Northern blot analysis identified a single transcript of approx. 1.4 kb, which was most abundant when cells were grown in media with glucose as the carbon source, as opposed to glycerol/lactate or ethanol. PMID- 7867937 TI - Isolation and characterization of the arginase-encoding gene (arg) from Coccidioides immitis. AB - The arginase (ARG)-encoding gene (arg) of Coccidioides immitis, a human fungal pathogen, was cloned and sequenced. Both the genomic and cDNA sequences are provided. The transcription start point and poly(A) sites were confirmed. The arg gene, which was located on chromosome II of C. immitis by Southern hybridization, is a single-copy gene with two introns and a 966-bp ORF which translates a 322-aa protein of 35.1 kDa. The deduced ARG protein showed 44% identity and 68% similarity to the Saccharomyces cerevisiae ARG. PMID- 7867938 TI - Dictyostelium discoideum contains a single-copy gene encoding a unique subtype of histone H1. AB - A Dictyostelium discoideum genomic library was screened using a degenerate oligodeoxyribonucleotide derived from the peptide, GPKAPT, obtained from the N terminus of purified histone H1. Two identical H1 clones were isolated. Comparative sequence data reveal a typical H1 three-domain structure with considerable homology to the globular domain of higher eukaryotic H1 histones, especially to plant H1 histones. Southern blot analysis shows that this gene is probably a single-copy gene, and suggests that any other H1 gene(s), if present, must be very different in sequence. Amino acid (aa) sequence comparison of the globular core of D. discoideum H1 to the consensus globular core reveals the absence of a 6-aa motif, GXGXXG, from D. discoideum. This motif matches the consensus for a putative nucleotide-binding loop, which is also absent in plant H1 histones like Arabidopsis thaliana, pea and wheat. PMID- 7867939 TI - Plasmid insertion vectors that facilitate construction of herpes simplex virus gene delivery vectors. AB - Plasmid insertion vectors were designed for the expression of foreign genes in recombinant herpes simplex virus (HSV) vectors. One vector, pGal9, was designed for the insertion of foreign genes with their own promoter; a second vector, pGal10, was designed for the insertion of coding sequences downstream from the HSV immediate-early 110K promoter. The 110K promoter directed efficient expression of foreign genes, particularly in replication-incompetent virus recombinants, as shown by the expression of the lacZ and IFN alpha genes. These vectors should be useful for the characterization of various promoters for gene delivery, and for the efficient expression of foreign genes in a variety of cell types. PMID- 7867940 TI - The revised nucleotide sequence of Tn5. AB - A re-examination of the IS50 sequence revealed nine single-bp changes from the original published sequence. The changes account for four replacements in the deduced amino-acid sequences of the Tn5 transposase and inhibitor protein. Both IS50L and IS50R are 1534 bp in length, and the total length of Tn5, therefore, is 5820 bp. PMID- 7867941 TI - The GCGGAA gene-regulatory motif of herpes simplex virus type-1 is also found in hepatitis C virus. AB - We have analyzed the sequence of the 5'-untranslated region of hepatitis C virus from 24 patients with chronic hepatitis C and we found a conserved six-nucleotide motif previously described as a modulator of gene expression. PMID- 7867942 TI - The Australian bushfly Musca vetustissima contains a sequence related to transposons of the hobo, Ac and Tam3 family. PMID- 7867943 TI - ToxR (RegA) activates Escherichia coli RNA polymerase to initiate transcription of Pseudomonas aeruginosa toxA. AB - The Pseudomonas aeruginosa (Pa) structural gene (toxA), which encodes the exotoxin A protein has been shown to be regulated at the transcriptional level by a protein designated ToxR (also known as RegA). We have previously reported that ToxR directly enhances toxA transcription in vitro; however, in the absence of ToxR, Pa RNA polymerase (RNAP) transcribes toxA with low efficiency. In the present study, we have examined the ability of ToxR to initiate toxA transcription using the heterologous Escherichia coli (Ec) RNAP and found that ToxR can function with Ec RNAP to efficiently transcribe toxA both in vitro and in vivo. Antibodies produced against the sigma 70 subunit of Ec RNAP inhibit ToxR mediated enhancement of toxA transcription, suggesting that the RNAP holoenzyme (E sigma 70) is required for transcriptional activation of toxA. We further demonstrate that ToxR is required for open-complex formation at the toxA promoter. By selectively deleting toxA upstream sequences, we have localized at 214-bp region containing both the toxA promoter and a putative ToxR-binding site sufficient for ToxR-mediated transcription of toxA. PMID- 7867944 TI - Cloning and characterization of a Bacillus thuringiensis homolog of the spoIIID gene from Bacillus subtilis. AB - The SpoIIID protein of Bacillus subtilis (Bs) is a small DNA-binding protein that is essential for gene expression of the mother cell compartment during sporulation. We have cloned a DNA fragment from Bacillus thuringiensis (Bt) that showed a specific hybridization with the Bs spoIIID gene. Sequence analysis found an open reading frame encoding 90 amino acids (aa), which are 89% identical to the deduced aa sequence of Bs spoIIID. Upstream from the transcription start point (tsp), a nucleotide sequence highly homologous to the consensus sequence motif for the sigma 35-recognized promoters was found. Northern blot analysis has indicated that the expression of the gene is induced only at the midsporulation stage, and that the gene constitutes an operon with a downstream gene, mreB. The Bs strain carrying the spoIIID delta erm or spoIIID83 mutation completely restored sporulation ability upon introduction of the spoIIID homologous gene from Bt. These results strongly suggest that the gene we have cloned is a Bt homolog of spoIIID. PMID- 7867945 TI - A fruiting body-specific cDNA, mfbAc, from the mushroom Lentinus edodes encodes a high-molecular-weight cell-adhesion protein containing an Arg-Gly-Asp motif. AB - A cDNA clone (designated mfbAc), encoding 2157 amino acids (aa), was isolated from a mature fruiting-body cDNA library of the edible mushroom Lentinus edodes. The mfbA transcript was abundant in mature fruiting bodies, detectable in immature fruiting bodies but absent in earlier developmental stages and in the vegetative mycelium. Although more abundant in the pileus than the stipe, only low levels were found in the gill tissue. The deduced MFBA protein (234.5 kDa) contained a cell-surface attachment-promoting Arg-Gly-Asp (RGD) motif. MFBA was produced in Escherichia coli using a maltose-binding protein (MBP) fusion vector, but it was cleaved into four fragments even in a protease-deficient host. A 425 aa MFBA peptide containing the RGD motif (named MFBA(582-1006) peptide) was successfully produced using the phage T7 expression system. This MFBA(582-1006) peptide exhibited a cell adhesion and spreading activity toward mammalian cells. This activity of the MFBA fragment was competitively inhibited by the Gly-Arg-Gly Asp-Ser-Pro peptide but not by the Gly-Arg-Gly-Glu-Ser-Pro peptide, showing that the RGD motif of MFBA is essential for the cell-binding activity. PMID- 7867946 TI - A calcineurin-B-encoding gene expressed during differentiation of the amoeboflagellate Naegleria gruberi contains two introns. AB - One of two similar genes in the unicellular eukaryote Naegleria gruberi is shown to encode calcineurin B (CnB), the regulatory subunit of calcium-calmodulin regulated protein phosphatase 2B. Over a span of 156 amino acids, excluding divergent N-termini, the encoded sequence shows 62% identity with vertebrate CnB, and also shows sequence elements specific, among calcium-binding proteins, to CnB. In contrast, the sequence shows only 23% identity with N. gruberi flagellar calmodulin. CNB mRNA is readily detected in amoebae; its abundance increases fourfold during differentiation to flagellates, reaches a peak at 50-70 min, when flagella are forming, and then declines. A genomic clone matches an expressed cDNA, except that it is interrupted by two phase I introns. The position of one intron, which separates the divergent N-terminal domain from the four calcium binding domains (EF hands), is shared with a yeast CNB gene; the other is located in the central helix between the two pairs of calcium-binding loops; features that support an ancient origin. These introns, the first found in protein-coding genes of Naegleria, are flanked by characteristic splice junction sequences. N. gruberi CnB also shares similarities with recoverins. The finding in a protist of a CNB gene that contains two introns separating functional domains, shares similarities to recoverins and shows increased expression during differentiation is provocative. If the phylogeny of major groups derived from ribosomal RNA is accepted, Naegleria is among the earliest branching eukaryotes known to contain canonical pre-mRNA introns. PMID- 7867947 TI - Transcriptional activation of the origin of coliphage lambda DNA replication is regulated by the host DnaA initiator function. AB - The initiator of phage lambda DNA replication, the lambda O protein, is considered to be an analogue of the initiator of DNA replication (DnaA) of its host, Escherichia coli. Both specifically recognize their origins of replication, ori lambda and oriC, respectively, and organize the assembly of specific replication complexes. However, DnaA has an additional activation function, acting on oriC-proximal DnaA-boxes, and regulating transcription initiated at promoters in and around oriC. Here, we demonstrate that lambda plasmid replication can be synchronized by a temperature shift-down that caused renaturation of the previously denatured DnaAts protein. Moreover, we show that elimination of the activating DnaA function affects transcriptional activation at ori lambda. DnaA may act by binding to DnaA-boxes, situated around the lambda pR promoter; there are no such sequences in ori lambda. Our results being to explain in molecular terms why lambda plasmid replication is DnaA-dependent [Kur et al., J. Mol. Biol. 198 (1987) 203-210] and why the initiation of phage lambda DNA replication is blocked (in E. coli devoid of prophage Rac) after inactivation of DnaA [Wegrzyn et al., Genetics (1995) in press]. PMID- 7867948 TI - Positive-selection vector with enhanced lytic potential based on a variant of phi X174 phage gene E. AB - A cloning vector, pUH89, allowing positive selection of recombinant Escherichia coli clones by insertional inactivation of the modified lysis gene E of bacteriophage phi X174, was developed. Ten unique cloning sites were introduced into gene E by site-directed mutagenesis. To achieve efficient expression of the mutagenized gene, the combined lac and tac promoters were used. Additional restriction sites in the flanking sequences allow screening for transcription terminators and the excision of several cartridges suitable for vector construction. PMID- 7867949 TI - The periplasmic endonuclease I of Escherichia coli has amino-acid sequence homology to the extracellular DNases of Vibrio cholerae and Aeromonas hydrophila. AB - The gene endA, encoding the periplasmic endonuclease I (EndoI) of Escherichia coli, was identified on a cloned chromosomal 1.5-kb HindIII fragment. The nucleotide sequence of the fragment revealed an open reading frame (ORF) coding for a polypeptide of 235 amino acids (aa). The ORF preceeded by a region with two possible promoter sites displays promoter activity when cloned into an expression vector. On the C-terminal side, two sequences with putative transcription termination function are present. The predicted aa sequence suggests the presence of a signal peptide of 22 aa and a signal peptide cleavage site. A cold-shock supernatant from cells harbouring a multicopy endA+ plasmid contained an approx. tenfold higher amount than wild-type cells of the DNA double-strand- and single strand-cleavage activities characteristic of EndoI. The growth rate and viability of the cells was not affected. The predicted aa sequence of the ORF is 60 and 54% identical to the sequence of extracellular DNases from Vibrio cholerae and Aeromonas hydrophila, respectively. PMID- 7867950 TI - Cloning and sequence analyses of the genes coding for the integration host factor (IHF) and HU proteins of Pseudomonas aeruginosa. AB - Histone-like proteins, such as HU and the integration host factor (IHF), are small, dimeric, DNA-bending proteins which play a role in maintaining constrained DNA structures and hence in regulating gene expression. Two different strategies were used to isolate the genes coding for Pseudomonas aeruginosa (Pa) HU and IHF, two proteins that we have previously isolated from a mucoid strain. By use of a PCR-based technique with oligodeoxyribonucleotides (oligos) designed from the N terminal amino acid (aa) sequences of HU and the beta-subunit of IHF, and Southern blot analyses, hupB and himD, encoding HU and IHF beta, respectively, have been cloned. The himA gene of Pa, encoding the alpha-subunit of IHF, was isolated using himA of Escherichia coli (Ec) as a probe in Southern blot analyses. The deduced hupB product (90 aa, 9 kDa) is 79% identical to HU beta and 61% to HU alpha of Ec. The predicted products of himA (100 aa, 11.5 kDa) and of himD (94 aa, 10.6 kDa) share 77 and 70% identity with IHF alpha and IHF beta of Ec, respectively. The promoter region of himD contains an IHF consensus sequence, as is the case for Ec himD. PMID- 7867951 TI - Sequence analysis of the gene cluster encoding toluene-3-monooxygenase from Pseudomonas pickettii PKO1. AB - The nucleotide (nt) sequence and gene organization of the locus encoding the initial step of the toluene-3-monooxygenase (Tbu) pathway from Pseudomonas pickettii PKO1 has been determined. This is the first reported nt sequence for a toluene monooxygenase which hydroxylates the C-3 position of toluene. Six tightly assembled structural genes encoding several Tbu were identified and were designated tbuA1, tbuU, tbuB, tbuV, tbuA2 and tbuC. Comparison of the deduced amino acid (aa) sequences of each open reading frame (ORF) with translated sequences from the GenBank database revealed significant overall homology to peptides from the toluene-4-monooxygenase (Tmo) from Pseudomonas mendocina KR1, the multicomponent phenol hydroxylase (Dmp) from Pseudomonas sp. strain CF600 and the methane monooxygenases (Mmo) from both Methylococcus capsulatus (Bath) and Methylosinus trichosporium OB3b. Similarities in both size and aa sequence between the peptides from these multicomponent oxygenases and the putative peptides from Tbu suggested roles for the TbuA1, TbuB, TbuV, TbuA2 and TbuC proteins. PMID- 7867952 TI - A new dhfrVIII trimethoprim-resistance gene, flanked by IS26, whose product is remote from other dihydrofolate reductases in parsimony analysis. AB - A new plasmid-borne gene, dhfrVIII, encoding high-level trimethoprim resistance (TpR) was found in an intestinal Escherichia coli. It seems to be a widely occurring mediator of TpR. Among 973 examined TpR E. coli, the new resistance gene was found in 13 (1.3%) isolates from Sweden, Finland and Nigeria. The new gene was sequenced and found to code for a dihydrofolate reductase (DHFR) of 169 amino acids (M(r) 19005). The dhfrVIII gene on the studied plasmid pLMO226 was observed to be flanked by IS26 elements. The dhfrVIII gene and a 3' unidentified open reading frame (ORF) seem to be borne on a compound transposon with IS26 at its ends, since the configuration of two IS26 flanking dhfrVIII and the unidentified ORF was conserved among the isolates that were probe-positive for the gene. Phylogeny parsimony analysis showed the dhfrVIII-encoded enzyme to be only remotely related to other known plasmid-mediated, drug-resistant DHFR. Only a few of the latter form well-supported monophyletic groups. PMID- 7867953 TI - Cloning, sequence and regulation of expression of the lexA gene of Aeromonas hydrophila. AB - The lexA gene of Aeromonas hydrophila (Ah) has been isolated by using a specific one-step cloning system. The Ah LexA repressor is able to block Escherichia coli (Ec) SOS gene expression and is likely to be cleaved by the activated RecA protein of this bacterial species after DNA damage. Ah lexA would encode a protein of 207 amino acids (aa), which is 75% identical to the LexA repressor of Ec. Two Ec-like SOS boxes have been located upstream from Ah lexA, the distance between them being 4 bp, whereas this same distance in Ec lexA is 5 bp. The structure and sequence of the DNA-binding domain of the LexA repressor of Ec, as well as the region at which its hydrolysis occurs, are highly conserved in Ah LexA. Moreover, a residue of the region implicated in the specific cleavage reaction, and which is present in all known RecA-cleavable repressors, is changed in the Ah LexA. Expression of Ah lexA is DNA-damage inducible in both the Ah and Ec genetic backgrounds to the same extent. In contrast, Ec lexA is poorly induced in DNA-injured Ah cells. PMID- 7867954 TI - Brevibacterium linens pBL33 and Rhodococcus rhodochrous pRC1 cryptic plasmids replicate in Rhodococcus sp. R312 (formerly Brevibacterium sp. R312). AB - The replication of two cryptic plasmids from Brevibacterium linens ATCC 9174 (pBL33) and Rhodococcus rhodochrous ATCC 4276 (pRC1) was investigated in Rhodococcus sp. R312 (formerly Brevibacterium sp. R312). The recombinant plasmids pSP33 (pBL33 derivative) and pSPC1 (pRC1 derivative) were found to be suitable for establishing new host-vector systems for Rhodococcus sp. R312. They all carry the Tn903 neomycin-resistance-encoding gene (aphI). PMID- 7867955 TI - Characterization of an acetyl-CoA C-acetyltransferase (thiolase) gene from Clostridium acetobutylicum ATCC 824. AB - Thiolase (Thl) is an important enzyme at the junction in the pathway leading to the production of either acids (acetate or butyrate) or solvents (acetone, butanol or ethanol) during the growth of Clostridium acetobutylicum ATCC 824. Cloning and expression of the Thl-encoding gene (thl) has been described [Petersen and Bennett, Appl. Environ. Microbiol. 57 (1991) 2735-2741], as has the purification and properties of the enzyme [Wiesenborn et al., Appl. Environ. Microbiol. 54 (1988) 2717-2722]. Here, we present the complete nucleotide sequence (1.9 kb) of thl. The gene encodes a protein of 392 amino acids (aa) (41,237 Da), which mass is in agreement with previous findings using the purified protein. Primer extension analysis has defined the promoter region, and a stem loop structure found at the end of thl indicates that it is not part of an operon. The aa sequence of Thl showed homology to those of four other beta ketothiolases: (i) PhbC of Alcaligenes eutrophus, (ii) PhbA of Chromatium vinosum, (iii) PhbA of Thiocystis violacea and (iv) PhbA of Zoogloea ramigera. The C terminus of an open reading frame found upstream from the Thl sequence is similar to OrfX of Bacillus subtilis and to NfrC of Escherichia coli. PMID- 7867956 TI - The vanZ gene of Tn1546 from Enterococcus faecium BM4147 confers resistance to teicoplanin. AB - A five-gene cluster from Tn1546 confers resistance to the glycopeptide antibiotics vancomycin (Vm) and teicoplanin (Te) by synthesis of pentadepsipeptide peptidoglycan precursors terminating in D-lactate, which replaces D-alanine in the same position of precursors utilized by susceptible enterococci. Cloning and nucleotide sequencing indicated that Tn1546 contains an additional gene, designated vanZ, which confers low-level Te resistance, in the absence of the genes required for pentadepsipeptide synthesis. Analysis of cytoplasmic peptidoglycan precursors, accumulated in the presence of ramoplanin, showed that VanZ-mediated Te resistance does not involve incorporation of a substituent of D-alanine into the precursors. PMID- 7867957 TI - Expression of a synthetic gene encoding P2 ribonuclease from the extreme thermoacidophilic archaebacterium Sulfolobus solfataricus in mesophylic hosts. AB - This work reports the molecular cloning and expression of a synthetic gene encoding P2, a 7-kDa ribonuclease (RNase) previously isolated in our laboratory from the archaebacterium Sulfolobus solfataricus [Fusi et al., Eur. J. Biochem. 211 (1993) 305-310]. The P2-encoding synthetic gene was expressed in E. coli and in Saccharomyces cerevisiae. The recombinant (re-) protein was produced to approx. 1.5% of the total protein content in S. cerevisiae using the galactose inducible GAL1 promoter and to 3% (tac/lac tandem promoters) or 6.5% (T7 promoter) in E. coli as judged by immunological and biochemical criteria. E. coli produced P2 was purified to electrophoretic homogeneity through a one-step procedure, i.e., DEAE-Sephacel chromatography at pH 9.3. S. cerevisiae-produced P2 additionally required filtration through a Centricon-10 microconcentrator to obtain the same purity. The re-P2 was found to be indistinguishable from the Su. solfataricus enzyme on the basis of heat stability, pH optimum and RNA digestion pattern. Furthermore, monodimensional nuclear magnetic resonance showed that the E. coli- and Su. solfataricus-produced enzymes were structurally identical, the only exceptions being that Lys4 and Lys6 were not methylated in the re-enzyme, thus showing that lysine methylation does not play a role in P2 thermostabilization. PMID- 7867958 TI - Aging of a class of arteries in various mammalian species in relation to the life span. AB - Age-related sclerosis of human renocortical arteries is associated with essential hypertension and limitation of the life span by cardiovascular mortality. Arteries in the kidneys of nonprimate species, examined here, showed near absence of arteriosclerosis when the average life span was less than 12 years and small amounts of sclerosis in longer-lived species. The fastest progression of arteriosclerosis was, paradoxically, in the longest-lived species, the human and the macaque. Results are incompatible with theories of aging that include arteriosclerosis within the framework of mechanisms that are proposed to explain the life spans of species. PMID- 7867959 TI - Neuromuscular control of lifting in the elderly. AB - The aim of this investigation was to determine, utilising an electromyographic (EMG) technique, the influence of the ageing process on the neuromotor control of the stoop-lift. Seven elderly (60-75 years) and seven young (18-25 years) subjects completed a series of ten unresisted (no weight) stoop-lifts. EMG potentials were recorded with 4-mm bipolar surface electrodes from the erector spinae and medial hamstring muscle groups. The temporal features of the stoop lift itself were recorded with an electrogoniometer. The results of this investigation showed that the elderly subjects had a significantly (p < 0.05) earlier onset of the erector spinae muscle during the up-phase of the stoop-lift compared to the younger subjects. In addition, reactivation of the erector spinae muscle in the up-phase occurred at hand positions significantly (p < 0.05) closer to the floor in the elderly group indicating more stooped postures. Thus the EMG profiles of the erector spinae within the elderly subjects performing unresisted stoop-lifts approximated those previously reported in younger subjects performing resisted (with a weight) lifting. The earlier onset of the erector spinae in the up-phase of the stoop-lift was partially explained by a significant (p < 0.05) reduction in flexibility (sit and reach test) associated with the elderly subjects. The results further stress the potential for injury associated with the utilisation of the stoop-lift, particularly by elderly populations. PMID- 7867960 TI - Principles of control and selection in mammalian aging. AB - Acquisition of immunologic self-tolerance by clonal deletion in the thymus is concluded to be a critical process in immune aging and is found to be transiently protected from genetic instability by means of a feedback surveillance which functions at the expense of chronic thymic involution. In the immune control of mammalian aging, principles of Darwinian natural selection are suggested to work at the cellular level. During life, an immune-mediated stabilizing cell selection is displaced by a destabilizing one, thus changing physiological to pathological aging. In consequence, mammalian aging may be approached from an evolutionary point of view by both genetic cell variation and immune selection and be revealed correspondingly both as a stochastic and programmed process. Age-dependent diseases may be characterized as the consequence of localized pathological aging. PMID- 7867961 TI - Antidepressant medicines for the elderly: are we using them appropriately? AB - We monitored antidepressant prescriptions to elderly patients over the age of 60 years admitted to a teaching hospital over a 3-months period. During this time we identified 48 patients taking antidepressant medication of whom 18 were started in hospital, the other 30 patients having had their therapy initiated before admission. In the hospital group, 1 in 3 was probably not depressed, as judged by using (Brief Assessment Scale Depression Cards), despite this screening having been made within 1 week of starting treatment. In the second group, i.e., those in whom treatment had been initiated before admission, 50% were still depressed in spite of prolonged treatment. We conclude that elderly patients should only be started on antidepressant therapy after careful assessment, and when prolonged treatment is considered necessary, it should be regularly evaluated for efficacy and psychiatric advice sought for those who fail to respond. PMID- 7867962 TI - Validity and reliability of the Winchester Disability Rating Scale (2). A comprehensive screening instrument for the elderly in the community. AB - Health and social services across the more developed countries in the world are facing the problem of providing care and support for an ever increasing elderly population. It has been suggested that this challenge would best be met by performing frequent 'assessment' of the total elderly population in a country. This would be very difficult and time consuming in a large country with a high number of elderly people. Screening using a broad coarse instrument aimed at identifying variations in dependency over time would be simpler, effective and more likely to be actually performed in the greatest majority of the target population. In developing firstly the Winchester Disability Rating Scale (WDRS) and then the WDRS-2, which includes a subscale for depression, we believe to have found an effective instrument to measure dependency and with it the means to limit hospitalization. We validated the WDRS-2 on a large sample of elderly people living in local authority housing schemes, and were able to demonstrate that our instrument has both high specificity and high sensitivity for the identification of depression in elderly people living in the community. This new instrument offers primary care physicians the opportunity to rapidly and successfully assess their elderly patients living in the community. PMID- 7867963 TI - Factors associated with falling in elderly hospital patients. AB - Forty-four patients aged 65 years and over who fell whilst in an acute hospital and 44 patients who did not fall during their hospital stay underwent structured medical examinations to identify factors associated with falling. The control subjects were matched for age (+/- 3 years), sex, patient type, and primary diagnosis. The examination was based on established assessments of posture, balance and gait, the musculoskeletal system, vision, cardiovascular status, and neurological function. Bivariate analyses revealed seven assessment measures that were significantly associated with falls: cognitive impairment, particularly impaired orientation; evidence of previous cerebrovascular accident; incoordination as measured clinically; inability to perform the 'Get-up-and-go' test, especially an inability to turn around after a 5-metre walk, and the use of psycho-active medications. Of these variables, impaired orientation, psycho active drug use, evidence of stroke, and impaired performance in the 'Get-up-and go' test were included in a stepwise logistic regression which correctly classified 80% of the patients into faller and non-faller groups. Falling was also related to the number of these identified risk factors. These findings suggest that a simple screening protocol, taking about 5 min to complete, can assist in the identification of patients at risk of falls whilst in hospital. PMID- 7867964 TI - Measurement of body composition in the elderly: dual energy x-ray absorptiometry, underwater weighing, bioelectrical impedance analysis, and anthropometry. AB - Body composition of both younger and older subjects was estimated using several different methods in order to evaluate their use with elderly subjects. Estimates were obtained by dual energy x-ray absorptiometry, underwater weighing, bioelectrical impedance analysis, and skinfold measurement in 48 younger subjects (26-40 years) and 44 older subjects (65-85 years). In older men and women the underwater weighing percent fat estimates were significantly higher than all other methods. Bone mineral explained a significant proportion of the variance in the difference between the dual energy x-ray absorptiometry and underwater weighing estimates of percent fat (R2 = 0.442-0.627). Because of its insensitivity to variability in bone mineral, we recommend that the underwater weighing method be not used to estimate percent fat in older men and women. Dual energy x-ray absorptiometry provides an alternative which accounts for the age related decrease in bone mineral density. PMID- 7867965 TI - Steroidogenic capacity and oxidative stress-related parameters in human luteal cell regression. AB - The steroidogenic capacity and oxidative stress-related parameters of the human corpus luteum (CL) at different stages of the luteal phase were studied under basal and human chorionic gonadotropin (hCG)-stimulated conditions. Mid CL exhibited the maximal steroidogenic capacity, together with lower levels of glutathione and higher thiobarbituric acid reactants content, macrophage count, and superoxide dismutase (SOD) activity, compared to the late CL. Addition of hCG to luteal cell cultures led to a preferential increase in progesterone synthesis in the late CL compared to the mid CL, without changes in the oxidative stress related parameters, except for the increased SOD activity found in the late CL. It is concluded that an oxidative stress condition is established in the mid CL, coinciding with the maximal steroidogenic capacity and macrophage infiltration of the organ, which may be of relevance as one of the major mechanisms initiating CL involution in the human. PMID- 7867966 TI - Polymorphonuclear leukocytes-induced injury in hypoxic cardiac myocytes. AB - Growing evidence suggests that free radicals derived from polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia-reperfusion injury. To elucidate the cellular mechanism by which activated PMNs exacerbate ischemic myocardial damage, we investigated the extent of cell injury, assessed by the morphological deterioration, free radical generation, and lipid peroxidation in mouse embryo myocardial cells coincubated with activated PMNs. The generation of PMN-derived free radicals was related to the extent of myocardial cell injury. When myocardial cell sheets were subjected to hypoxia and glucose-free media, myocardial cells were injured (cristalysis in the mitochondria and disruption of the sarcolemma) after adding various PMN activators, and the injury extended to the adjacent cells. Chemiluminescent emission and production of thiobarbituric acid-reactive substances in the coincubated cells increased markedly compared with myocardial cells or PMNs alone. The augmented lipid peroxidation coincided with the progression of myocardial cell injury. Catalase inhibited the myocardial cell injury by 52%, the chemiluminescence by 46%, and lipid peroxidation by 50%, whereas superoxide dismutase exhibited less pronounced inhibition. These results indicate that a chain reaction of lipid peroxidation in myocardial cells induced by PMN-derived free radicals closely correlates with membrane damage and contributes to the propagation of irreversible myocardial cell damage. PMID- 7867967 TI - Oxidative stress decreases antioxidant enzyme activities in reaggregation cultures of rat brain cells. AB - The brain has been suggested to be especially sensitive to damage by reactive oxygen species. In this study, we examined the effects of hyperoxic conditions on the activities and mRNA levels of antioxidant enzymes in reaggregation cultures of rat forebrain cells. Cultures were exposed to 80% oxygen for 12-60 h starting on Days 17 and 33 in culture. Superoxide dismutase activities and mRNA levels were not affected by hyperoxia, whereas catalase activity was slightly decreased after 24 h in 80% oxygen at Day 17. Glutathione peroxidase activity was markedly decreased already after 12 h of hyperoxia, and decreased activities of glutathione reductase and glucose-6-phosphate dehydrogenase were also noted. The glutathione peroxidase mRNA levels were increased in hyperoxic cultures at Day 17 but not at Day 33. These results suggest that the enzymatic defense mechanisms against reactive oxygen species in the brain are rather weak and deteriorate during oxidative stress but that a potential for compensatory upregulation exists at least during the first postnatal weeks. PMID- 7867968 TI - Antioxidant action of sodium diethyldithiocarbamate: reaction with hydrogen peroxide and superoxide radical. AB - The oxidation of sodium diethyldithiocarbamate (DDC) by hydrogen peroxide or superoxide radicals has been investigated. Hydrogen peroxide oxidizes DDC, leading to the formation of a hydrated form of disulfiram, a dimer of DDC having a disulfide group. In equimolar conditions, the overall process appears as a first-order reaction (k = 0.025 +/- 0.005 s-1), the first step being a second order reaction (k = 5.0 +/- 0.1 mol-1.1.s-1). No radical intermediate was observed in this process. In the presence of an excess of any of the reagents, the hydrated form of disulfiram transforms into different products corresponding to the fixation of oxygen by sulfur atoms or replacement of C = S group by ketone function, in the presence of an excess of hydrogen peroxide. Superoxide anions (produced by steady-state 60Co gamma-radiolysis) oxidize DDC, yielding similar products to those obtained with hydrogen peroxide with a maximum oxidation G value of 0.3 mumol.J-1. The rate constant k(O2.- + DDC) is equal to 900 mol-1.1.s 1. PMID- 7867969 TI - Weak antioxidant defenses make the heart a target for damage in copper-deficient rats. AB - Copper deficiency causes more salient pathologic changes in the heart than in the liver of rats. Although oxidative stress has been implicated in copper deficiency induced pathogenesis, little is known about the selective toxicity to the heart. Therefore, we examined the relationship between the severity of copper deficiency induced oxidative damage and the capacity of antioxidant defense in heart and liver to investigate a possible mechanism for the selective cardiotoxicity. Weanling rats were fed a purified diet deficient in copper (0.4 microgram/g diet) or one containing adequate copper (6.0 microgram/g diet) for 4 weeks. Copper deficiency induced a 2-fold increase in lipid peroxidation in the heart (thiobarbituric assay) but did not alter peroxidation in the liver. The antioxidant enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase were, respectively, 3-, 50- and 1.5-fold lower in the heart than in the liver, although these enzymatic activities were depressed in both organs by copper deficiency. In addition, the activity of glutathione reductase was 4 times lower in the heart than in the liver. The data suggest that a weak antioxidant defense system in the heart is responsible for the relatively high degree of oxidative damage in copper-deficient hearts. PMID- 7867970 TI - Effects of a carotene-deficient diet on measures of oxidative susceptibility and superoxide dismutase activity in adult women. AB - The effect of consuming a low carotene diet (approximately 60 micrograms carotene/day) on oxidative susceptibility and superoxide dismutase (SOD) activity in women living in a metabolic research unit was evaluated. The diet had sufficient vitamins A, E, and C. The women ate the diet supplemented with 1500 micrograms/day beta-carotene for 4 days (baseline), then the unsupplemented diet for 68 days (depletion), followed by the diet supplemented with > 15,000 micrograms/day carotene for 28 days (repletion). Production of hexanal, pentanal, and pentane by copper-oxidized plasma low density lipoproteins from carotene depleted women was greater than their production of these compounds when repleted with carotene. Erythrocyte SOD activity was depressed in carotene-depleted women; it recovered with repletion. Thiobarbituric acid reactive substances in plasma of carotene-depleted women were elevated and diminished with repletion. Dietary carotene seems to be needed, not only as a precursor of vitamin A, but also to inhibit oxidative damage and decrease oxidation susceptibility. PMID- 7867971 TI - Reactive radical intermediates formed from illuminated nifedipine. AB - Nifedipine, (1,4-dihydro-2,6,dimethyl-4-(2-nitrophenyl)-3, 5-pyridinedicarboxylic acid dimethyl ester) a calcium channel blocker widely used in treatment of hypertension, is strongly photolabile. This may represent a problem in patients taking nifedipine and in handling of nifedipine samples. Reactive radical intermediates were determined and characterized in the process of nifedipine illumination using EPR spectroscopy. On illumination of nifedipine by daylight or by a mercury lamp, a nitroxide radical, RIIL-NIFNO.X was observed (in the first step), in various solvents like benzene, cyclohexane, methanol, acetonitrile, dimethylsulphoxide, or aqueous suspensions of liposomes. RIIL-NIF represents the nifedipine skeleton centered with phenyl group, and X is an EPR silent substituent. The generation of RIIL-NIFNO.X is coupled with the formation of nitroso compound, RIIL-NIFNO, as characterized by UV-visible spectroscopy. In a further step, RIIL-NIFNO abstracts hydrogen from nifedipine skeleton under the formation of RIIL-NIFNO.H radical. In addition to this, in system containing RIIL NIFNO and unsaturated lipids, nitroxide radicals RIIL-NIFNO.RLIPIDS are formed probably via a pseudo Diels-Alder mechanism (RLIPIDS represents lipidic skeleton). The unusually easy photochemical activation of nifedipine is probably stimulated by photosensitization of its nitro group interacting with suitably positioned hydrogen or carboxylic methyl ester group from the pyridinyl ring. PMID- 7867972 TI - Hydrogen peroxide-mediated inactivation of microsomal cytochrome P450 during monooxygenase reactions. AB - Cytochrome P450 can undergo inactivation following monooxygenase reactions in liver microsomes of untreated, phenobarbital and 3-methylcholanthrene-treated rats and rabbits. The acceleration of cytochrome P450 loss in the presence of catalase inhibitors (sodium azide, hydroxylamine) indicates that hydrogen peroxide is involved in hemoprotein degradation. It was revealed that cytochrome P450 is inactivated mainly by H2O2 formed through peroxy complex breakdown, whereas H2O2 formed via the dismutation of superoxide anions produces a slight inactivating effect. The hydrogen peroxide added outside or formed by a glucose glucose oxidase system has less of an inactivating effect than H2O2 produced within the cytochrome P450 active center. Self-inactivation of cytochrome P450 during oxygenase reactions is highly specific. Other components of the monooxygenase system, such as cytochrome b5, NADH- and NADPH-specific flavoproteins, undergo no inactivation. The alterations in phospholipid content and in the rate of lipid peroxidation were not observed as well. The inactivation of cytochrome P450 by H2O2 is the result of heme loss or destruction without cytochrome P420 formation. Such a mechanism operates with different substrates and cytochrome P450 species catalyzing the partially coupled monooxygenase reactions. PMID- 7867973 TI - Breath ethane generation during clinical total body irradiation as a marker of oxygen-free-radical-mediated lipid peroxidation: a case study. AB - Total body irradiation (TBI) is used therapeutically for treatment of leukemias and other malignancies of the hemopoietic system. Ionizing radiation produces oxygen free radicals that contribute to cytotoxicity. Breath collected from one patient undergoing therapeutic TBI showed measurable changes in levels of ethane during treatment. Breath ethane is a marker of lipid peroxidation of n-3 fatty acids. The TBI treatment involved 4 days of irradiation. The largest changes in breath ethane occurred on Day 2. The increased levels of breath ethane on Day 2 were correlated to clinical manifestations of toxicity. The correlation of the onset of gastrointestinal side effects with higher levels of breath ethane suggests that breath ethane may be a clinically useful measure of the toxicity of various TBI fractionation treatment protocols currently in use at different medical centers. The levels of breath ethane on the other days of treatment were lower, suggesting that the oxidative-antioxidative balance of the patient may be important in protection against free radical mediated injury. These results for a single patient suggest that breath ethane may be a promising approach to elucidate the role of antioxidants in clinical TBI and should be extended for verification to a larger volunteer patient population. PMID- 7867974 TI - The protective potency of two commonly used cardioplegic solutions on cultured endothelial cells exposed to free-oxygen radicals injury. AB - Human umbilical vein endothelial cells were incubated with Bretschneider and St. Thomas II cardioplegic solution followed by a stimulation with cumene hydroperoxide (CHPO), which was used as an oxygen radicals generating agent. A statistically significant decrease of intracellular high energy phosphates (adenosine-5-trisphosphate: ATP; creatine phosphate: CP) compared to controls was observed in response to Bretschneider cardioplegia and CHPO. Furthermore, significant rises in prostaglandin I2 (prostacyclin; PGI2) production and lipidperoxidation were measured. The authors failed to record such alterations of endothelial cell metabolism for the St. Thomas II cardioplegic solution. They could also demonstrate that the cellular protection against oxygen radicals exerted by the St. Thomas II solution is attributable to procaine. The enhanced cytotoxicity of CHPO observed in presence of the Bretschneider solution was found to be partially caused by its constituent L-histidine, which led to significant decreases of high energy phosphates and increased lipidperoxidation when cells were subsequently treated with CHPO. However, alterations of high energy phosphate content initiated by CHPO and amplified by the Bretschneider solution could not be inhibited by adding procaine. Simultaneous pretreatment of cells with the Bretschneider solution and procaine and stimulation with CHPO resulted in decreases of ATP and CP, as observed using the Bretschneider cardioplegia alone. PMID- 7867975 TI - Kinetic evaluation of lipophilic inhibitors of lipid peroxidation in DLPC liposomes. AB - The authors have developed a kinetic method that allows one to obtain relative reactivity constants for lipophilic antioxidants in free radical systems. Two experimental model systems were developed: (a) a methanolic solution using AMVN as the free radical initiator and linoleic acid as the substrate, and (b) a multilamellar vesicle system composed of dilinoleoylphosphatidylcholine and AAPH as the substrate and the initiator, respectively. The use of these two systems allows researchers not only to determine the intrinsic reactivity of a potential antioxidant, but also to evaluate its potency in a membranous system where the contribution of the physical properties of the antioxidant to the inhibition of lipid peroxidation is important. These results show that all antioxidants tested acted in these systems as free radical scavengers, and they validate the synergism between intrinsic scavenging ability and membrane affinity and/or membrane-modifying physical properties in the inhibition of lipid peroxidation. PMID- 7867976 TI - Reaction of 4-hydroxynonenal with some thiol-containing radioprotective agents or their active metabolites. AB - The rate of reaction of several radioprotective agents or their active metabolites with 4-hydroxynonenal (4HNE) was studied and compared to the rate of reaction with cysteine (Cys) and glutathione (GSH). The agents studied were: mercapto ethylamine (MEA); 2(3-aminopropyl) aminoethanethiol (WR1065); S-2 aminoethylisothiouronium bromide-hydrobromide (AET); 1,4-dithiothreitol (DTT); 1,4-dithioerythritol (DTE); N-2(2-mercaptopropionyl)-glycine (MPG); penicillamine hydrochloride (PA); N-acetylcysteine (NAC); 2-3 dimercapto-1 propane sulfonic acid (DMPS); 2,3-dimercaptopropanol (BAL), and meso 2,3 dimercapto succinic acid (DMS). All of them reacted with 4HNE. MEA and WR1065 were the most reactive thiols, and PA and DMS were the least reactive thiols. All the others reacted at rates comparable to or higher than that of cysteine or GSH. The potential role of this type of interactions in the protective action of these drugs against deleterious effects of radiation or carbon tetrachloride is analyzed. PMID- 7867977 TI - 3rd Congress of the Italian Society of Experimental Hematology. Udine-Grado, September 22-24, 1994. Abstracts. PMID- 7867978 TI - [External fixation in reconstructive hand surgery]. AB - Over the last two decades, a new type of treatment has been established in reconstructive surgery of the hand. By means of an external fixator used as a distraction device, thumb and fingers are reconstructed. Used as a compression device, the external fixator accelerates the treatment of pseudarthroses, posttraumatic deformities, chronic osteomyelitis and healing following arthrodesis in the hand. There is no universal external device for the hand. Each part of the hand needs a specific fixator. Two basic questions require further studies: Improvement of the external fixators. Acceleration of the callus formation in the distraction method. PMID- 7867979 TI - [Reconstruction of the traumatically amputated thumb by continuous Matev distraction. Experiences and results in 48 cases]. AB - Continuous distraction can be considered as an alternative method of thumb reconstruction after traumatic loss. This technique is applicable if at least two thirds of the metacarpal length are retained and the stump is well covered by soft tissue. Elongation up to 100% of the initial length is then realizable. For a good functional precision grip it is necessary for the reconstructed thumb to reach the nail root of the opposite side. There is normal tactile gnosis after distraction. The strength of power grip is not decreased. Impaired, however, is the skillfulness of pulp-to-pulp pinch. We report on our experience in 48 cases. PMID- 7867980 TI - [Distraction lengthening in brachymetacarpia. Case report]. AB - A 16-year-old female patient with a congenital short fourth metacarpal in the right hand was successfully treated by distraction-lengthening. A transverse osteotomy was performed with daily incremental distraction of 0.5 to 1.0 mm, and the distractor device was in place for altogether 12 weeks. The fourth metacarpal was lengthened by 2 cm. The X-ray analysis one year later demonstrated normal skeletal structure. Distraction-lengthening has a number of advantages, when compared with one- or two-stage interposition bone grafting. PMID- 7867981 TI - [Pathology of the sesamoid bones of the hand]. AB - Sesamoid bones are osseous parts of certain joints and can either be included in pathological changes of these joints or separately in those of the sesamoidal joint itself. The clinical relevance of such findings is described in the following examples: Rheumatoid variants, psoriasis, different types of hyperostotic forms, chronic sesamoiditis as well as post-trauma. In three out of four cases of fracture, the ulnar sesamoid bone of the metacarpophalangeal joint of the thumb was affected. PMID- 7867982 TI - [Hand injury in polytrauma. A retrospective study of 782 cases]. AB - The incidence of hand injuries in multiple trauma is not well investigated. Between 1980 and 1986, 782 multiple trauma patients received primary treatment at the University Hospital of Erlangen. At the time of the study, 22% (n = 173) of these patients had died. 93% of the patients met with a traffic accident. In 20% of the multiple trauma patients, additional hand injuries were seen. 75% of these injuries were closed fractures of hand and wrist. The severity of multiple trauma had no influence on the incidence of hand injury. Young people between twenty and fourty years of age were mostly affected in multiple trauma, with increased incidence of hand injuries especially after motorcycle accidents. Delay of diagnosis of hand injuries was rare. PMID- 7867983 TI - [Wrist para-articular radioulnar arthrodesis with distal Kapandji ulnar resection]. AB - In 19 patients, the Sauve-Kapandji procedure was performed between 1990 and 1993. The most important indication was the painful and restricted forearm rotation after fracture of the distal radius combined with dislocated or destroyed radio ulnar joint. 18 patients were followed up. The only failure was found in a patient with bony regeneration across the resected ulnar segment and non-union of the distal radio-ulnar joint fusion. In all other cases, we found reduction of pain, an improved forearm rotation and grip strength. PMID- 7867984 TI - [Reconstruction of grip function in bilateral complex explosion injury]. AB - Evaluation, therapeutical possibilities, and surgical planning for the restoration of bilateral grip function are described, based upon the case of a blind patient presenting after severe bilateral explosion injuries of the hand with grade 3-4 loss of thumbs and fingers. Finally, the given level of amputation and remaining components of the hand together with toe transplantation permitted restoring of power grip on one side and fine grip on the other side in combination with bone and soft-tissue procedures. PMID- 7867985 TI - [Possibilities for using the first dorsal metacarpal artery in acute management of severe hand injuries]. AB - Two new indications for the first dorsal metacarpal artery are demonstrated in two cases with severe hand injuries. In the first case, an index pollicization was performed on the dorsal pedicle, in the second case a "kite" flap from the index finger was successfully microsurgically anastomosed. PMID- 7867986 TI - [Hypercalcinosis of the hands in scleroderma. 2 case reports]. AB - Hypercalcinosis of the hand in association with scleroderma represents a rare and benign soft-tissue calcification. Reported are two cases of symmetric affection of soft-tissue layers of both hands in association with scleroderma. Superinfection and exulcerations necessitated surgical treatment. Diagnosis, therapy, and progress are described. PMID- 7867987 TI - Effect of a balanced amino acid-based diet on the nitrogen metabolism in carbon tetrachloride-induced liver injury. AB - In experimental study, in white rats with carbon tetrachloride-induced injury of the liver, branched-chain amino acids of vegetable origin were found to display hepatoprotective activity against the CCL4 toxic effect. They reduced the ammonia and glutamine concentrations in the blood and brains of the experimental animals and caused a significant decrease in the concentration of the aromatic amino acids (phenylalanine and tyrosine) in the animals' brains. The results of the study indicate that branched-chain amino acids are related to the pathogenesis of hepatic encephalopathy. PMID- 7867988 TI - Morphology of the Haversian canal. An electron microscopic study. AB - Electron microscopic study of the Haversian canal and its content was performed. Four types of wall lining cells were identified: undifferentiated lining cells, resting mature osteoblasts, active osteoblasts, osteoblast-osteocytes which represented different stages in the differentiation process of the fibrilogenetic cell population. The narrow space between the lining cells and the mineralized bone tissue contained randomly oriented collagen fibrils arranged in layers. Such arrangement of the fibrils determined the lamellar model of the osteons prior to their mineralization. The perivascular space contained both poorly differentiated and mature fibrilogenetic cells with numerous cytoplasmic processes as well as collagen fibrils with different orientation. The cells and the fibrils formed networks which were the sites of the metabolic exchange between the blood vessels and the bone tissue. This process was realised in the medium of the interstitial fluid which filled the perivascular space. All these make the perivascular space an important link of the osteon microcirculation. PMID- 7867989 TI - Secondary diabetes in children with thalassaemia major (homozygous thalassaemia). AB - Life expectancy of patients suffering from homozygous beta-thalassaemia has been improved due to the modern treatment of this disease. This has allowed development of late hemosiderosis-related complications and disturbances of the endocrine and exocrine functions of the pancreas. Carbohydrate metabolism of 16 patients with thalassaemia major was studied. Three of them presented with a pronounced clinical picture and biochemical constellations of a severe diabetes mellitus. The remainder had no clinical symptoms of carbohydrate metabolism disorders. The pancreatic beta-cell function of the patients was assessed by measuring the serum concentrations of immunoreactive insulin and by a glucose tolerance test. Most patients showed very low basal insulin levels while glucose tolerance was reduced in only one of them. In this patient we also established delayed insulin response after an intravenous glucose load. We concluded that the disturbed insulin secretion found in the children studied is most likely the earliest manifestation of the pancreatic beta-cell insufficiency which precedes the changes in the glucose tolerance. PMID- 7867990 TI - Blindness in different types of eye disease. A study based on the records of the Department of Eye Diseases in the Medical University, Plovdiv for the period 1982 1991. AB - Between 1982 and 1991, inclusive, a total of 13718 patients were treated in the Department of Eye Diseases in Plovdiv University of Medicine. Cataract patients formed the most numerous group (19.71%), followed by those with diseases of the retina (9.53%), glaucoma (7.95%), uveitis (4.9%), diseases of the cornea (3.86%), malignant tumors of the eyelids and the eyeball (2.29%) and diseases of the optic nerve (1.54%). Of these 13718 patients, 1727 (12.58%) had monocular and binocular vision below 0.08. The patients with visual acuity from 0 to 0.03 were 1330 (9.69%). Nosologically, they were distributed as follows: glacoma-422 (3.07%), eye traumas-281 (2.04%), diseases of the retina-270 (1.96%), diseases of the cornea-89 (0.64%), cataract-80 (0.58%), uveitis-77 (0.56%), malignant tumors of the eyelids and the eyeball-66 (0.48%), and diseases of the optic nerve-45 (0.32%). Glaucoma was found to be the most common cause of blindness among the patients treated in the Department of Eye Diseases, followed by eye traumas and disease of the retina. The importance of the vascular factor in inducing blindness is undeniably great. It is the underlying cause of the open-angle glaucoma, the diseases of the retina and the optic nerve. PMID- 7867991 TI - Clinical problems of infectious complications in patients with multiple myeloma. AB - Infectious complications in 126 patients with multiple myeloma were studied throughout the entire course of the disease. Various infectious complications were found in 71 patients (56.3%). They had predominantly pulmonary (42%) and renal (37%) localisation. Most commonly, they were manifested in the acute stages of the myelomatosis: the onset of the disease, during and after the induction therapy, the relapses and in the terminal stage. Using various biologic, clinical, immunologic, biochemical, therapeutic and prognostic criteria all patients presenting with infectious complications were compared with the rest of the patients. Statistically significant risk factors for an infectious process were shown to be old age, the disease in its third clinical stage, light chain myelomas, secretion of lamda light chains, leucopenia, azotaemia, polyclonal suppression of immunoglobulins and inadequate therapeutic response. The infection complications do not have significant impact on the survival of myeloma patients. PMID- 7867992 TI - Hypercalcaemia and azotaemia in multiple myeloma--clinical and biochemical parallels. AB - 109 patients with multiple myeloma were studied. In 35 (32%) of them calcium level was elevated above 2.65 mmol/l and increased significantly with the clinical stage of the disease. A various degree of nitrogen retention, which was not statistically significantly dependent on the clinical stage, was found in 65 (56%) patients. There was a moderate positive correlation (r = +0.46) between the renal failure and Bence Jones proteinuria. In 27 patients, 77% of the hypercalcaemic and 44% of the azotaemic patients, both the calcium level and azotaemia were increased. In the patients with reversible and partially reversible azotaemia the occurrence of hypercalcaemia as well as the absolute values of serum calcium and creatinine showed parallel dynamics after treatment. The progression of calcaemia with the increase of nitrogen retention is a characteristic feature of renal failure in multiple myeloma. Hypercalcaemia and azotaemia are mutually interacting pathogenetic factors and the correction of increased calcium level is a must in modern therapeutic strategies. PMID- 7867993 TI - New parameters for evaluation of oxygen transport on the dissociation curve of human blood. AB - Three new parameters were applied to evaluate oxygen transport using the dissociation curve of human blood. They are derived from the following equation: [formula: see text] The first parameter, beta 1,0, reflects the oxygen capacity of the curve within the range of 1.0 kPa at its "arterial section". The second parameter, beta 2,3, reflects the oxygen transport from the "arterial" point to the point of extraction of 2.3 mmol/l-1 of oxygen which is assumed as normal. The third parameter, beta 5-4 kPa, characterises the oxygen transport at the "venous" section of the curve. The parameters were studied on a cohort of 12 healthy people and 141 patients with chronic obstructive pulmonary disease at different stages of respiratory failure. A significant correlation was found between the oxygen capacity parameters, beta 1,0 and beta 2,3, and pO2(a), sO2 and the calculated transpulmonary shunt. They were not influenced by ctHb and ctO2(a). beta 5-4 showed marked correlation with the hemoglobin and total O2 concentration and the parameters that indicate a risk of tissue hypoxia-px and Qx. Standardisation of the new parameters with ctO2(a) correlates it functionally with the parameters of oxygen affinity. PMID- 7867994 TI - The trauma-surgery interval--implications for the outcome of traumatic intracranial hematomas. AB - The time that elapses between trauma and the beginning of surgical treatment is the interval during which traumatic intracranial hematomas are clinically manifested and diagnosed and the patients are prepared for surgical treatment. This trauma-surgery interval is divided into two periods: a diagnostic period and a period of preparation for surgery. A total of 610 patients treated in the Neurosurgery Department of the Plovdiv University of Medicine between 1975 and 1990 were retrospectively studied. They are allocated into groups of patients who survived or died during the trauma-surgery interval and patients treated during the consecutive stages of diagnostic capabilities of the Department: 1975-1979, 1980-1981, and 1982-1990. The study suggests that utilization of all methods of making a diagnose results in early identification of the hematoma and shortening of the diagnostic period of the trauma-surgery interval. This enables surgeons to operate on patients with acute hematomas at the earliest possible time after the trauma, achieving better therapeutic results. In patients with chronic hematomas the shorter diagnostic period makes it possible to devote the relatively expanded part of the trauma-surgery interval for preoperative preparation during which some concomitant disorders can be treated. Thus the risks from general anesthesia and the operative interventions are reduced. PMID- 7867995 TI - A case of interhemispheric subdural hematoma. AB - The interhemispheric subdural hematoma is a rare condition. We present a case of interhemispheric subdural hematoma in a patient aged 65 years. A day prior to admission he was struck with a water-pipe on the head. He went to sleep the same evening complaining of a slight headache. At about two o'clock in the morning the headache increased in intensity. By the morning he lost consciousness. On examination by a neurosurgeon the patient was found to be comatose. The physical examination revealed blue eyelids of the left eye, paraplegia of the right leg, paresis of the left leg and arms. Bilateral Babinski's reflex was present, the abdominal reflexes were absent, the tendon and periosteal reflexes were hyperactive. The pupils were equal in size and slowly reactive to light. The patient exhibited symptoms of meningoradicular irritation. An emergency CT scan revealed high-density area in the interhemispheric sulcus extending frontally to parietally. The patients was operated on in an emergency. At operation, extensive rupture of the sagittal sinus was identified. Later the patient died. The presented case was interesting with the extensive rupture of the sagittal sinus and the relatively long lucid interval until clear manifestation of the clinical picture becomes evident. PMID- 7867996 TI - Oral hygiene and gingiva status in school children aged 7 to 14 from Plovdiv. AB - An assessment of the oral hygiene and periodontal health was made in 1596 school children (777 boys and 819 girls) aged 7-14 years from randomly selected classes and schools in Plovdiv, Bulgaria. The oral hygiene status of the school children assessed by the plaque indexes (PLI) of J. Greene and J. Vermillion, and that of J. Silness and H. Loe was found to be rather poor. The relative share of subjects with plaque index of 0.00 to 1.00 was found to increase with age for both sexes. The relative share of children with chronic catarrhal gingivitis was 42.61 +/- 2.34 indicating the necessity of active prophylaxis and treatment of the disease. A tendency was observed towards an increase of the disease incidence in comparison with data obtained in a 1983 study. A correlation between the hygiene status and chronic gingival inflammation in 14-year-old school children was found. PMID- 7867997 TI - Scientific meetings of the Francophone Society of Primatology and the Primate Society of Great Britain. 1993 and 1994. Abstracts. PMID- 7867998 TI - Regulation of hepatic cytochrome P4501A by indole-3-carbinol: transient induction with continuous feeding in rainbow trout. AB - This study investigated the kinetics of hepatic cytochrome P-4501A (CYP1A) induction in rainbow trout by indole-3-carbinol (I3C), a natural tumour modulator from cruciferous vegetables, and its low pH reaction products 3,3' diindolylmethane (I33'), 5,6,11,12,17,18-hexahydrocyclononal[1,2-b:4,5-b':7,8 b"]triindo le cyclic trimer (CT), and the unresolved I3C acid reaction mixture (RXM). RXM, CT and I33' were potent inducers of total embryonic CYP1A following direct microinjection, and of fingerling hepatic CYP1A following ip exposure, whereas I3C itself produced only a transient and relatively weak induction. It is also reported for the first time that dietary I3C induced hepatic CYP1A and its associated ethoxyresorufin O-deethylase (EROD) activity in trout but, again, the induction was weak and transient even with continuous I3C feeding. Mechanism studies and mixed exposures with the Ah agonist beta-naphthoflavone indicated that transient induction by I3C was not due to diet ageing, but appears to involve inactivation of the Ah inductive pathway and irreversible inactivation of CYP1A-mediated EROD activity by I3C-derived metabolites. Thus, I3C derivatives exhibit dual capacities for CYP1A induction and inhibition in trout. PMID- 7867999 TI - Haemorrhagic toxicity of a large dose of alpha-, beta-, gamma- and delta tocopherols, ubiquinone, beta-carotene, retinol acetate and L-ascorbic acid in the rat. AB - Antioxidants occasionally have become prooxidants when a large amount was ingested. The haemorrhagic toxicity of butylated hydroxytoluene, a synthetic antioxidant, may involve such a mechanism. This study investigated whether haemorrhage is induced by overdoses of tocopherols, beta-carotene, ubiquinone or L-ascorbic acid, which are representative biological antioxidants. Male Jcl:SD rats (six rats/group) were fed d-alpha, d-beta, d-gamma or d-delta-tocopherols, ubiquinone Q-10, beta-carotene or retinol acetate at a level of 0.5%, or L ascorbic acid at 5% in the diet for 7 days. Only two rats given retinol acetate died with lung haemorrhages. Haemorrhages were observed in five or six, six, one, one, one or one of six surviving rats given d-alpha, d-beta or d-gamma tocopherols, ubiquinone Q-10, beta-carotene or retinol acetate, respectively (except for a retinol group in which four rats survived). Major haemorrhages were noted in the epididymis. In the alpha-, beta- and gamma-tocopherol, ubiquinone Q 10, beta-carotene or retinol acetate-treated groups, prothrombin and kaoline activated partial thromboplastin time indices were 26-28, 37, 59, 42, 63 and 65% or 27-28, 35, 65, 38, 59 and 28%, respectively, of the control values. Only the prothrombin index was significantly decreased to 67% in delta-tocopherol administered rates, whereas controls and those receiving L-ascorbic acid showed no signs of bleeding or coagulation defect. The same tendency was also seen in the decreasing effect on vitamin K-dependent blood coagulation factors. These results suggest that the four naturally occurring tocopherols have a tendency to cause haemorrhage in the order of alpha > beta > gamma > delta, and ubiquinone Q 10 and beta-carotene als0o have relatively strong and weak haemorrhagic effects, respectively, with regard to prothrombin and partial thromboplastin time indices. PMID- 7868000 TI - Effects of polyethylene glycol 400 (PEG 400) following 13 weeks of gavage treatment in Fischer-344 rats. AB - Fischer-344 rats (10/group/sex) were administered polyethylene glycol 400 (PEG 400) by gavage at 1.0, 2.5 or 5.0 ml/kg (1.1, 2.8 and 5.6 g/kg, respectively) body weight/day 5 days/wk for 13 wk. Animals in the control group received water by gavage (5.0 ml/kg body weight/treatment day). An additional 10 rats/sex/group were assigned to the control and high-dose groups for a 6-wk recovery period. Evaluation of potential renal toxicity was identified as a primary objective. There was no mortality or changes in haematology or clinical chemistry measurements attributed to PEG 400 toxicity. Loose faeces in the mid- and/or high dose group of both sexes were attributed to bulk cathartic effects of PEG 400. Slight decreases in food consumption and body weights in the mid- and/or high dose group of male rats and female rats were attributed to the physical presence of PEG 400 in the intestinal tract. However, a direct effect of PEG 400 on the intestinal tract was not ruled out. Increased water consumption was attributed to a possible increase in serum osmolality due to the absorption of the PEG 400 or a reflection of the water dosing received by the control animals. Increased urinary concentration and decreased urinary pH were at least partially attributed to absorption, possible metabolism, and urinary excretion of PEG 400. Small increases in absolute and/or relative kidney weights observed in many dose groups, were attributed to the osmotic effect of the test substance and/or metabolites in the urine. The significance of a slight increase in relative kidney weights in female rats following the recovery period was unknown. Although no microscopic changes were observed in the kidneys or urinary bladder, a slight, reversible renal toxicity may have resulted in male rats treated by gavage with 2.5 ml/kg/day and rats of both sexes treated by gavage with 5.0 ml PEG 400 kg/day. This was based on the increased concentration of protein and bilirubin, urinary vascular cell findings and N-acetyl-beta-D-glucosaminidase activity. PMID- 7868001 TI - Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate in rats and mice. AB - Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate were studied in male F344 rats and B6C3F1 mice. Benzyl acetate was rapidly hydrolysed to benzyl alcohol and then oxidized to benzoic acid. After gavage administration of benzyl acetate in corn oil at 500 mg/kg (rats) and 1000 mg/kg (mice), high benzoic acid plasma concentrations were observed. In contrast, much lower benzoic acid plasma concentrations were found after dosed feed administration at about 615 mg/kg/day for rats and about 850 mg/kg/day for mice. Results show that although the daily doses of benzyl acetate are comparable, bolus gavage administration effectively saturated the benzoic acid elimination pathway whereas dosed feed administration did not. In contrast, hippuric acid plasma concentrations were similar after both gavage and dosed feed administration due to the depletion of the glycine supply pool. Study results could explain the different toxicity and carcinogenicity responses of benzyl acetate observed in 2-yr chronic gavage and dosed feed studies. PMID- 7868002 TI - Effect of ingestion of 20 pesticides in combination at acceptable daily intake levels on rat liver carcinogenesis. AB - Exposure of agricultural workers and the general population to pesticides is a major concern, and possible summation or synergistic effects deserves particular attention. In this study, however, combined dietary administration of 19 organophosphorus compounds and one organochlorine pesticide, each at acceptable daily intake (ADI) levels, did not enhance rat liver preneoplastic lesion development initiated by diethylnitrosamine. In contrast, a mixture of 100 times ADI significantly increased the number and area of lesions. The results thus provide direct support for the present safety factor approach to the quantitative hazard evaluation of pesticides. PMID- 7868003 TI - Rat strain differences in catechol carcinogenicity to the stomach. AB - The carcinogenic potential of catechol was compared in male Wistar, WKY, Lewis and SD strains of rats. Groups of 30 animals were treated with powdered diet containing 0.8% catechol for 104 wk and then examined histopathologically. Induction of glandular stomach adenocarcinomas occurred in 67, 73 and 77% of Wistar, Lewis and SD animals, respectively, but in only 10% of WKY rats. In addition, catechol induced forestomach papillomas in 20% (P < 0.05), and squamous cell carcinomas in 3% of SD rats. The results thus indicate that Wistar, Lewis and SD rats are much more susceptible than WKY rats to induction of glandular stomach adenocarcinomas by 0.8% catechol, and that this phenolic antioxidant also possesses weak carcinogenic activity for the SD rat forestomach. PMID- 7868004 TI - Induction of oxidative DNA damage and early lesions in rat gastro-intestinal epithelium in relation to prostaglandin H synthase-mediated metabolism of butylated hydroxyanisole. AB - The effect of metabolic activation of the food additive 3-tert-butyl-4 hydroxyanisole (BHA) by prostaglandin H synthase on the gastro-intestinal cell proliferation was determined by studies of the nature and the time dependency of early lesions in the forestomach, glandular stomach and colon/rectum of rats given BHA with and without co-administration of acetylsalicyclic acid (ASA: an inhibitor of prostaglandin H synthase), in combination with the formation of oxidative DNA damage in the epithelial cells of glandular stomach and colon/rectum as well as in the liver. BHA appeared to be a strong inducer of oxidative DNA damage in the epithelial cells of the glandular stomach, increasing the level of 7-hydro-8-oxo-2'deoxyguanosine (8-oxodG) with increasing duration of BHA administration. Similar observations were made in colorectal DNA although levels of oxidative DNA damage tend to be smaller. In liver DNA, BHA appeared to be capable of increasing background 8-oxodG levels only after 14 days of treatment. This relatively slow response may be related to very low prostaglandin H synthase activity of liver cells. The severity of hyperplasia and inflammation in both forestomach and glandular stomach appeared to increase gradually with continued BHA administration. The hyperplasia induced by BHA was paralleled by inflammatory changes. In colorectal tissue, however, no tissue abnormalities were observed. This indicates that oxidative DNA damage induced by BHA is not a consequence of early lesions in gastro-intestinal epithelium, but might be the initial step in the stimulation of gastro-intestinal cell proliferation which, as shown previously, also occurs in colon epithelium. Co-administration of the prostaglandin H synthase inhibitor ASA resulted in a significant decrease of both epithelial oxidative DNA damage and the incidence of lesions, which indicates that this enzyme system is involved in the enhancement of cellular proliferation induced by BHA. Co-oxidation by prostaglandin H synthase of the BHA-metabolite tert-butylhydroquinone into tert-butylquinone, yielding active oxygen species, might therefore be responsible for the carcinogenic effects of this food antioxidant. PMID- 7868005 TI - The pathophysiology of cocaine cardiotoxicity. AB - Cocaine use is accompanied by a high risk of serious adverse effects involving the cardiovascular system. The basic cellular mechanisms of cocaine consist in [1] a potentiation of catecholamine effects by inhibition of the presynaptic uptake carrier [2] local anesthetic effects by the block of sodium-channels. Acute ischemic events can be induced by cocaine through coronary spasms in a situation of physiologic stress already accompanied by an enhanced myocardial oxygen demand. Procoagulant properties of cocaine may, moreover, favor coronary thrombosis formation and the development of myocardial infarction. Ischemia, reperfusion and the direct action of catecholamines on cardiocytes are accompanied by enhanced cytoplasmic calcium levels, inducing delayed after potentials, repetitive action-potential generation and premature ventricular beats. Conduction velocity impairments caused by the local anesthetic effects of cocaine and inhomogeneous repolarization phenomena related to potassium channel inhibition may form a substrate for re-entrant circuits inducing ventricular fibrillation. Cocaine abuse may also cause degenerative and inflammatory alterations of the myocardium. Besides secondary ischemic changes, hypersensitivity-myocarditis and toxic cardiomyopathies that may be due to the cardiotoxic effects of catecholamines have been described in cocaine abusers. Moreover, persons using cocaine intravenously seem to be particularly endangered by bacterial endocarditis compared to the users of other intravenous drugs, for still unknown reasons. PMID- 7868006 TI - The epidemiology of homicide-suicide (dyadic death). AB - The national and international rates of homicide and homicide-suicide (dyadic death) have been studied by examination of the available literature. The rates of homicide-suicide episodes between different countries showed considerable variation, though not as great as overall homicide rates. Despite the variation the features of the episodes were similar, with a man usually killing his spouse and/or children with a firearm. The commonest motive for killing is jealousy and/or revenge, often as the result of a breakdown in the spousal relationship. PMID- 7868008 TI - Chinese population data on three tetrameric short tandem repeat loci--HUMTHO1, TPOX, and CSF1PO--derived using multiplex PCR and manual typing. AB - Allele and genotype frequencies for three tetrameric short tandem repeat (STR) loci were determined in a Chinese sample population using multiplex polymerase chain reaction (PCR), electrophoresis of the PCR products in DNA sequencing gels and subsequent detection by silver staining. The loci are HUMTHO1, TPOX, and CSF1PO. All loci meet Hardy-Weinberg expectations. In addition, there is no evidence for association of alleles among the three loci. The allelic frequency data can be used in human identity testing to estimate the frequency of a multiple STR locus DNA profile in the Chinese population. PMID- 7868007 TI - Quantitation of nucleotides, nucleosides and bases in antemortem and postmortem bloodstains by high-performance liquid chromatography. AB - Ante- and post-mortem bloodstains prepared from the blood of volunteers and corpses were analysed for ATP and its related compounds by reversed-phase high performance liquid chromatography (HPLC). The results showed that (1) ATP was present in a large amount in antemortem bloodstains but not in postmortem stains, (2) AMP, adenosine, inosine, hypoxanthine, xanthine and uracil either were not detected or were detected in smaller amounts in antemortem than in postmortem bloodstains, and (3) ADP was present in both ante- and post-mortem bloodstains. These differences suggest that quantitation of these compounds may be useful in identifying whether bloodstains are ante- or post-mortem. PMID- 7868009 TI - Report on the second EDNAP collaborative STR exercise. European DNA Profiling Group. AB - The European DNA Profiling Group (EDNAP) has previously carried out collaborative exercises to determine which STR systems will produce results that can be reproduced by different laboratories. The first EDNAP exercise involving STR systems focused on different types of loci: a simple locus with six common alleles (HUMTH01) and a complex locus with > 35 alleles (ACTBP2). Generally the simpler STR system was found to be readily amenable for use across a wide range of different technologies, whereas a more complex locus presented difficulties. The second EDNAP STR exercise was intended to take the process of investigation a stage further. Some laboratories are developing automation, coupled with fluorescent methods of detection and multiplex applications, whereas others use manual methods involving visual detection techniques such as silver staining. The purpose of this exercise was to determine whether loci amenable to multiplexing with automation (as a quadruplex reaction) could also be successfully used with manual methods, either by multiplexing in duplex reactions or alternatively by using just a single pair of PCR primers. PMID- 7868010 TI - Allele frequency distribution of four PCR-amplified loci in the Spanish population. AB - The allele frequency distributions of four VNTR loci amplified by PCR have been studied in a population of 205 individuals from Spain. The loci analysed are D1S80 and three STRs: HUMTH01, HUMFES/FPS and HUMACTBF2 (SE33). The former was visualized in Metaphor agarose gels, and the STRs in sequencing polyacrylamide gels under denaturing conditions which could separate alleles with differences of a single base. This is of particular importance in the HUMTH01 locus, a tetrameric STR in which two alleles (9.3 and 10) were detected differing in a single base. Furthermore, HUMACTBP2 has at least 30 alleles, some of which may vary by as little as one base. At this locus a variation in the allele mobility was observed, depending on the electrophoretic conditions. For this reason, there should be careful consideration before this marker is accepted and validated as a common interlaboratory system. This paper does not include any comparison of the frequencies obtained for this locus with other recent studies. For the rest of the loci, the frequencies found have been compared with other published population studies; they show a degree of difference, particularly in the D1S80 locus. Finally, the systems were tested for Hardy-Weinberg equilibrium, and some statistical parameters of forensic interest were calculated. PMID- 7868011 TI - Investigation of bloodstains: false negative results of the benzidine test. PMID- 7868012 TI - Immunohistochemical detection of C5b-9(m) in myocardium: an aid in distinguishing infarction-induced ischemic heart muscle necrosis from other forms of lethal myocardial injury. AB - Immunohistochemical detection of C5b-9(m) is a reliable marker of very early cell necroses due to myocardial infarction. However, it is conceivable that it is also present in myocardial cell necroses caused by other types of hypoxic injury or by direct external trauma. If so, this would greatly limit the diagnostic value of C5b-9(m) in forensic practice. To clarify this issue, we performed immunohistological staining for C5b-9(m) in myocardium of 67 cases of 'direct' or possible 'indirect' myocardial injury not due to infarction. PMID- 7868013 TI - A case of internal beveling with an exit gunshot wound to the skull. AB - Exit gunshot wounds of the skull generally have external beveling while entrance wounds show internal beveling. With rare exceptions, entrance gunshot wounds show external beveling, usually of two types: the asymmetric 'keyhole' type and the symmetric 'non-keyhole' type. In exit gunshot wounds of the skull, only the keyhole type has been reported. This report shows that symmetric internal beveling from an exit gunshot wound to the skull may confuse medical personnel. PMID- 7868014 TI - A comment from the front lines in Vermont. PMID- 7868015 TI - Health care reform in The Netherlands, Sweden, and the United Kingdom. AB - The experiences of three European countries that are actively engaged in reforming their health care systems--the Netherlands, Sweden, and the United Kingdom--point to a degree of convergence in the types of reforms being pursued. European experiences also offer a number of lessons for the United States. These include the importance of government intervention in the health care market to ensure universal coverage, the key role of primary care in ensuring access to basic health services and in containing costs, and the need to create a strong purchasing or insurance function to hold providers accountable on behalf of patients. The pace and scope of reform are affected significantly by the political process in each country. PMID- 7868016 TI - Risk-adjusted capitation: recent experiences in The Netherlands. AB - The market-oriented health care reforms taking place in the Netherlands show a clear resemblance to the proposals for managed competition in U.S. health care. In both countries good risk adjustment mechanisms that prevent cream skimming- that is, that prevent plans from selecting the best health risks--are critical to the success of the reforms. In this paper we present an overview of the Dutch reforms and of our research concerning risk-adjusted capitation payments. Although we are optimistic about the technical possibilities for solving the problem of cream skimming, the implementation of good risk-adjusted capitation is a long-term challenge. PMID- 7868017 TI - The shadow of the future: institutional change in health care. PMID- 7868018 TI - National health spending trends, 1960-1993. AB - In 1993 the nation spent $884.2 billion on health care, a 7.8 percent increase from 1992. Although this spending growth was among the lowest rates of growth recorded since 1960, it is too soon to tell whether slower growth in health spending is a new trend or merely a temporary perturbation in the long-term trend. The portion of the economy devoted to health care increased from 13.6 percent in 1992 to 13.9 percent in 1993--a 0.3 percentage point increase that equaled the average rate of increase recorded since 1960. The federal government's share of the total health care bill rose between 1991 and 1993, the first significant change in the share of the nation's health care bill funded by the federal government since the early 1970s. PMID- 7868019 TI - Small employers and the health insurance market. AB - In 1993 half of all small businesses (fewer than fifty workers) sponsored a health plan for their employees, up from 41 percent in 1989. While not as deep, the benefits offered by small firms are nearly as broad as benefits offered by large firms, and they have expanded since 1989. Small businesses pay more for coverage, however. Although coverage restrictions based on health status and preexisting conditions are a significant concern of small firms, actual limits of this type in the small-group market are modest. Firms not offering insurance report that they have wide access to coverage, and many would sponsor a plan if only prices were lower. PMID- 7868020 TI - Excess cost of emergency department visits for nonurgent care. AB - After examining data for patients with selected conditions and statistically adjusting for patient, diagnosis, and treatment characteristics, this Data Watch finds that charges for emergency department visits were two to three times more than charges for visits in other settings. Large differences persist when conditions are examined individually and when total episode charges are examined. Based on our findings, a rough estimate of nationwide excess charges is $5-$7 billion for 1993. PMID- 7868021 TI - Measuring outpatient mental health care in the United States. AB - A standard definition of outpatient mental health care does not now exist. Data from the 1987 National Medical Expenditure Survey are used to examine how varying the definition influences utilization estimates. A broad definition of mental health care, which requires purchase of a psychotropic medication or a psychotherapy visit or a visit for a mental health condition, captures nearly seven times as many persons as a definition that requires a visit to a mental health specialist for a mental health condition and either purchase of a psychotropic medication or psychotherapy. Because estimates of mental health service use are highly sensitive to how treatment is defined, caution should be exercised in evaluating mental health utilization data. PMID- 7868023 TI - Use of the resource-based relative value scale for private insurers. AB - Medicare's resource-based relative value scale (RBRVS) was implemented 1 January 1992 for physician payment using a conversion factor of $31 for each relative value unit (RVU). We calculated a conversion factor of $42.24 for The Travelers Insurance Company's group health plan business using the RBRVS methodology and the calendar year 1990 Travelers Large Case Norms Extract of active employees. This DataWatch describes two important applications of the relative value scale for private insurers: for pricing and for analyzing claims expenditures. PMID- 7868022 TI - Impact of extending health care coverage to the uninsured. AB - Changes in use of health services by the uninsured, when covered after health reform, are a key to the costs of reform. From data on persons under age sixty five in the 1989 National Health Interview Survey, we estimated their expected use of hospitals (excluding obstetric deliveries) and doctor visits, adjusting for age, sex, and self-reported health status. If uninsured persons obtained private coverage distributed by the plan type of other persons in their home regions, nonobstetric hospital days for the formerly uninsured would increase 28 percent, and their visits to physicians' offices would increase 52 percent. If instead the uninsured enrolled entirely in group- or staff-model health maintenance organizations (HMOs) in their home regions, their nonobstetric hospital days would actually decrease 17 percent, and their visits to physicians' offices would increase 60 percent. PMID- 7868024 TI - Measuring state health spending: another look. PMID- 7868025 TI - Use of state-specific data for policy: the author responds. PMID- 7868026 TI - Feasibility of long-term care insurance partnerships. PMID- 7868028 TI - Addressing the malpractice problem: the Robert Wood Johnson Foundation's programs. PMID- 7868027 TI - Passing the 'laugh test' for long-term care insurance partnerships. PMID- 7868029 TI - An agenda for federalism from state leaders. Reforming States Group. PMID- 7868030 TI - Risk adjustment in Germany. PMID- 7868031 TI - OB-GYNs as primary care physicians: a mixed blessing. PMID- 7868033 TI - Cost of medical advances. PMID- 7868032 TI - Addressing the spectrum of women's health needs. PMID- 7868034 TI - Technology assessment and outcomes research. PMID- 7868035 TI - 'Nimble and resourceful' technology assessment. PMID- 7868036 TI - Is health spending slowing down? AB - We analyze trends in real per capita health care spending. Using a different and, we believe, more appropriate adjustment for trends in general inflation than the Health Care Financing Administration (HCFA) analysts use, we reach a different conclusion: The purported slowdown in health care spending in the 1990s is modest at best through 1993. Other measures of health care spending, such as the medical care Consumer Price Index, private health care premiums, and hospital cost growth, are unreliable measures of overall health care spending. PMID- 7868037 TI - Health care reform and the Medicare program. AB - None of the health care reform bills introduced during the last session of Congress would have ended the deepening Medicare fiscal crisis. Delays in resolving Medicare's fiscal problems will increase generational inequities and cause disruptions in health care delivery. Because of the pressures of increasing health care costs on government, business, and individuals, comprehensive health care reform will be deliberated in future sessions of Congress. It remains to be seen, though, whether policymakers will be able to develop reforms that address the basic problem of rising health care costs. PMID- 7868038 TI - Delving into health expenditure trends: two approaches. PMID- 7868040 TI - The subterranean role of health care reform. PMID- 7868039 TI - The new world of managed care: creating organized delivery systems. AB - In response to managed care pressures and imminent legislative reforms, provider organizations across the United States are coming together to form organized or integrated delivery systems. This paper describes various approaches to developing such systems and, drawing on ongoing research, examines what is known about the performance of such systems, the barriers they face, and the key factors likely to be associated with their success. The paper also addresses important policy questions related to the extent to which organized delivery systems should be actively encouraged by health reform legislation and how such systems should be held accountable. PMID- 7868041 TI - Changing course in turbulent times: an interview with David Lawrence. Interview by John K. Iglehart. PMID- 7868042 TI - Health spending analysis: thinking straight about medical costs. PMID- 7868043 TI - Health care reform in Vermont: the next chapter. AB - It seemed inconceivable that Vermont would not enact comprehensive health care reform in 1994. Two years earlier the Vermont legislature had created the Vermont Health Care Authority to prepare the groundwork for major reform. Yet the 1994 Vermont General Assembly could not reach agreement on legislation. What went wrong? Some on the political left and right say that the legislature stopped "bad" legislation. The Vermont story reveals the failure of reformers to convince interest groups and ordinary citizens about the capacity of government to reform the health system. PMID- 7868044 TI - [Several medical problems for ideal relationship between breast cancer patients and surgeons in Japan]. AB - Recently, breast cancer is one of the most important disease in Japanese women. It is now recognized from prospective studies that Japanese women are at an increased risk of developing breast cancer. In this paper, the author mentioned the several problems of Q.O.L., informed consent and medical system for breast cancer patients in Japan. It is well-known that the patients with recurrent breast cancer showed low level of Q.O.L. compared with the patients free from the disease. So it is important to make a good result of the recurrent rate of conservative treatment of breast cancer as well as radical mastectomy. PMID- 7868045 TI - [To establish confidential relationship between physician and patient: how should be in future?]. AB - Nearly 10 years have passed since I was hospitalized for two months to have a surgery of the Ano-Rectum. Meantime, suffering from severe physical pain at the early postoperative days followed by various anxieties throughout the time of hospitalization, I could see and learn that daily warm talks and kind behaviors of the nurses and doctors in charge were very impressive. The doctor's adequate and precise explanation on the disease and surgical procedure to be selected was quite understandable and also agreeable for me. Then, I could have a firm confidence in all treatments of the doctor. Fortunately, I could return to the routine work as a surgeon without much difficulties after surgery. Recently, I have been appointed as the director of the hospital which is now under replacement to improve the system and design of the ward. In this chance, I am doing my best to modify the system and design as much as possible by considering and reflecting all needs and desires of the patients, some of which are originated from my own experiences as a patient 10 years ago. PMID- 7868046 TI - [To establish confidential relationship between physician and patient: as a patient undergone an operation]. AB - In October 1990, I was diagnosed as malignant gastric lymphoma and was admitted into Hokkaido University Hospital and underwent surgery. Among many memories of my stay in the hospital, the most reassuring moment was that my doctor expressed his sincere thoughts to work with me as a partner in fighting the illness. The surgeon in charge of my surgery visited my room every day and explained all the details, so I was able to undergo the operation without fear. Needless to say, the cheerful talk and care of the nurses throughout my stay in the hospital supported me. It has been about four years after the operation and I am currently healthy and working. The following points are my requests for better medical practice. 1) A reduction in the amount of waiting time for outpatients. 2) Improvement of amenities for admitted patients. 3) An increase in efficiency of examination for the treatment. 4) Work harder and become a good doctor, and improvement of younger doctors. PMID- 7868047 TI - [Effective doctor-patient interaction and communication: psychiatric point of view]. AB - Effective interaction and communication between doctor and patient is a central clinical function that cannot be delegated. Most of the essential diagnostic information arises from the interview, and the physician's interpersonal skills also largely determine the patient's satisfaction and compliance and positively influence health outcomes. Such skills, including active listening to patient's concerns, are among the qualities of a physician most desired by patients. Increasing public dissatisfaction with the medical profession is, in good part, related to deficiencies in clinical communication. Sufficient data have now accumulated to prove that problems in doctor-patient interaction and communication are extremely common and adversely affect patient management. It has been repeatedly shown that the clinical skills needed to improve these problems can be taught and that the subsequent benefits to medical practice are demonstrable, feasible on a routine basis, and enduring. There is therefore a clear and urgent need for teaching of these clinical skills to be incorporated into medical school curriculums and continued into postgraduate training and courses in continuing medical education. If current knowledge is now implemented in clinical practice, and if the priorities for research are addressed, there may be material improvement in the relationship between patient and doctor. PMID- 7868048 TI - [Special comments on physician-patient relation]. AB - Medical practice is only possible on well-informed consent between doctor and patient, for which doctor should first of all be a good listener of patient's physical and mental anguishes. Good listening can bring about genuine communication between doctor and patient, and tell doctor how to improve amenity of patient's hospital living. It is hoped that medical care system in Japan will turn out in future so that patients (consumers of medical care) will sort out doctors not only for their medical skill but for their ability of providing communication and amenity for patients. PMID- 7868049 TI - [The patients' right of self-decision and the discretion of physicians]. AB - I attended the 10th liaison society of ethics committees in medical schools in Japan. Three topics on the problems of the terminal patients, Jehovah's Witness needing blood transfusion and the patients suffering from AIDS were discussed by symposists consisted of 6 physicians, 2 nurses and a jurist. I picked up key phrases from the symposists' presentations with respect to professions. The physicians used the terms of terminal care, quality of life, informed consent, etc. The nurses emphasized a labor shortage, an ideal physician, cooperation of the patient's family, etc. A jurist expressed euthanasia, death with dignity, right of living and dying, etc. The common issue relating with all terms would be "patient's right of self-decision". Physicians should recognize this right and then exercise their discretion. All patients should be regarded as social beings under the medical care, which would be realized when physicians treat diseases with the relevant patients. PMID- 7868050 TI - [Cultural background of the Japanese bioethics]. AB - We attended the 11th Liaison Society of Ethics Committees in Medical Schools in Japan. Three symposiums were held under the themes of quality of life (QOL), stopping medical cure and the Japanese bioethics. Symposists were medical practitioners, teaching staffs in universities and a person of religion. In the first symposium, the definition of QOL, the usage of the term and the method of its evaluation were discussed. In the second symposium, an internist and a neonatologist reported several cases and stated problems and countermeasures in terminal care in cases that they could not maintain QOL. A person of religion made his opinion on the problems. In the final symposium were stated Japanese bioethics from the aspects of ethics and cultural anthropology. They emphasized differences in bioethical view between the Japanese and the Europeans and Americans, and a need to reform medical education in Japan. It is difficult to define QOL and to care patients at terminal stage, because present-day persons have various senses of value. Especially, Japanese have taken Western culture into our traditional social structures with its original style. Therefore, we have dual culture, as recognized in communication. Although it is very important to communicate sufficiently between patients and doctors, we consider that the dual communication has interrupted their mutual understandings. Incidentally, Western medicine had originally dual structure of art and technology. But we have taken only the technological aspect. That is probably the reason why human relations have been getting worse. It would be necessary for us to attend to these two dual structures in order to solve bioethical problems in Japan. PMID- 7868051 TI - [Regulatory mechanism of non-shivering thermogenesis in cold acclimation--with special reference to in vitro thermogenic activity and lipolysis of brown adipose tissue]. AB - In vitro brown adipose tissue (BAT) thermogenesis from cold-acclimated (CA) rats has been shown to exhibit the decreased responses to noradrenaline (NA) and glucagon (G), although an enhanced biochemical machinery for thermogenesis develops in the tissue. The present study was undertaken to clarify the inhibitory mechanism of in vitro thermogenic responses of BAT in CA rats. NA treated rats were injected NA (40 micrograms/100g BW) twice a day for 2 or 4 weeks. The other rats were kept at 25 +/- 1 degree C (warm controls: WC), 5 +/- 1 degree C (CA), or 5 +/- 1 degree C/6h/day (intermittent cold exposure: ICE) for 5 6 weeks. The oxygen consumption, and glycerol as well as free fatty acids (FFA) release were measured on finely minced tissue blocks in Krebs-Ringer phosphate buffer at 37 degrees C. In vitro BAT thermogenic responses to NA and G in NA treated rats did not differ from those in vehicle-injected controls. NA as well as G increased-oxygen consumption was greatest in WC, followed by ICE and CA. NA as well as G increased glycerol and FFA releases in WC and ICE, but the degree of increment was greater in WC than that in ICE, while NA or G did not increase glycerol and FFA releases in CA. FFA/glycerol ratio in WC was decreased by NA as well as G, but it was not changed in ICE, and increased in CA. Mitochondrial GDP binding as an index of BAT thermogenic capacity did not differ between CA and WC under resting state (CA rats were transferred in warm condition before 18h at the beginning of the experiment), but it was significantly greater in ICE. GDP binding was significantly greater in CA sacrificed at 5 degrees C compared with WC and CA resting. Acute cold exposure (5 degrees C/1h) enhanced GDP binding in WC, resting CA and ICE resting, but the degree of increment was greater in CA and ICE than in WC. These findings suggest that cold exposure inhibits BAT thermogenic responses according to the duration NA action during cold exposure, by means of suppressing fatty acid utilization and/or masking uncoupling protein. PMID- 7868052 TI - [Nutritional adaptation in brown adipose tissue thermogenesis--with special reference to overfeeding and iron deficiency]. AB - The effect of sucrose overfeeding and low iron diet on brown adipose tissue (BAT) thermogenesis of rats has been investigated from the view point of in vitro BAT oxygen consumption and BAT fatty acids (FA) compositions in rats. Control group was fed on a standard diet with tap water, sucrose group was on the standard diet and 32% sucrose solution, and iron deficient group on a low iron diet with tap water. In vitro interscapular BAT thermogenesis as estimated by oxygen consumption was measured in minced tissue blocks in Krebs-Ringer phosphate buffer using a Clark oxygen electrode. In sucrose overfeeding rats, caloric intake was greater than in controls, but did not differ body weight. Interscapular BAT weight and DNA content were greater. Colonic and tail skin temperatures were higher. Basal oxygen consumption was higher. Noradrenaline- and glucagon stimulated oxygen consumptions did not differ when expressed per DNA, but significantly greater per whole tissue pad. Both BAT-triglyceride (TG) and phospholipid (PL) levels were higher. Polyunsaturated FA were lower, while monosaturated FA were higher in both BAT-TG and -PL. In iron deficient rats, BAT weight and DNA content were higher. Colonic and tail skin temperatures did not differ. Although basal oxygen consumption did not differ, noradrenaline stimulated oxygen consumption was less per DNA, but did not differ per whole tissue pad, while glucagon-stimulated oxygen consumption was less when expressed per DNA, as well as whole tissue pad. Cold-tolerance as assessed by the fall in colonic temperature at 0 degree C was decreased. BAT-TG and -PL levels did not differ. Polyunsaturated FA were higher in both BAT-TG and -PL. These findings indicated that sucrose-induced overfeeding enhances BAT thermogenesis mainly by tissue hyperplasia, while iron deficiency suppresses BAT thermogenic response, although it causes the compensatory tissue hyperplasia. PMID- 7868053 TI - [Distribution of herpes simplex virus type 1 and 2 genomes in the human spinal ganglia]. AB - Herpes simplex virus (HSV) is well known for its propensity to cause recurrent oral or genital mucosal infections in humans. HSV-1 is involved primarily in oral lesions, whereas HSV-2 is more frequently involved in genital lesions. Based on this, it is thought that HSV-1 may produce latent infections in trigeminal ganglia, and HSV-2 in the sacral ganglia. However the distribution pattern of latent HSV-1 and HSV-2 infections in spinal ganglia remains unknown. Using the polymerase chain reaction we detected latent herpes HSV-1 and HSV-2 in human spinal ganglia obtained from autopsy material. A pair of primers which were specific for a part of the HSV-1 and HSV-2 DNA polymerase domain were employed. HSV-1 and HSV-2 DNAs were detected in 11 of 40 (28%) and 15 of 40 (38%) cervical ganglia, respectively, 52 of 103 (50%) and 47 of 103 (46%) thoracic ganglia, 16 of 53 (30%) and 17 of 53 (32%) lumbar ganglia, and 3 of 20 (15%) and 3 of 20 (15%) sacral ganglia. These findings suggest that latent HSV-1 and HSV-2 infections have a widespread distribution from the cervical ganglia to sacral ganglia. Importantly this study demonstrated latent HSV-1 infection of both the lumbar and sacral ganglia for the first time. PMID- 7868054 TI - [Pharmacological studies on alterations in myocardial beta-adrenoceptors and their intracellular signal transduction in experimental diabetic rats]. AB - The present study was undertaken to determine abnormalities which are responsible for the diminished functional responsiveness to beta-adrenoceptor stimulation in experimental diabetic rats. Rats were given an intravenous injection of 45mg/kg streptozotocin and hearts were removed from 4 to 6 weeks later. The positive inotropic effects of isoproterenol, norepinephrine and epinephrine were markedly depressed in diabetic rat papillary muscles. Diabetic cardiac muscles also exhibited a reduced maximum contractile responses to forskolin, 3-isobutyl-1 methylxanthine and dibutylic cyclic AMP. The density of beta-adrenoceptors in membranes prepared from diabetic hearts was decreased by 40%, with uniform decreases in the beta 1- and beta 2-subtypes. The affinity of the receptor for the radioligand antagonist [125I]-iodocyanopindolol remained unchanged. Competition binding studies with isoproterenol did not reveal a difference in the fraction of beta-adrenoceptors with high-affinity binding between control and diabetic cardiac membranes, suggesting that interaction between beta adrenoceptors and Gs may be preserved well in the diabetic state. All measures of adenylate cyclase activity showed that beta-adrenoceptor-dependent and Gs dependent cyclic AMP productions are well maintained in membranes from diabetic hearts. Thus, these data suggest that the decreased positive inotropic response to beta-adrenoceptor stimulation in diabetic hearts is not attributable to changes in beta-adrenoceptor-Gs-adenylate cyclase system but rather may be due to an alteration in cellular function beyond the level of cAMP generation. To test this hypothesis, incorporation of [32P]-inorganic phosphate into phospholamban in sarcoplasmic reticulum was examined in Langendorff-perfused hearts. Isoproterenol (100nM) increased phosphorylation of phospholamban threefold in control hearts, but did not cause a significant change in the phosphorylation state in diabetic hearts. From these findings it is concluded that the decreased functional responses to cyclic AMP-increasing agents like beta-adrenoceptor agonists in diabetic hearts may be associated with impaired phosphorylation of cardiac regulatory phosphoproteins including phospholamban. PMID- 7868055 TI - [Analysis of birch pollen allergen]. AB - Birch Pollen is one of common causal agents of nasal allergy (pollinosis) in Hokkaido, Japan. We have previously reported the positive association of the pollinosis with HLA-DR9 antigens. It was reported by others that Bet vI, a 17kDa protein with known amino acid sequences represented the major allergen of birch pollen in Europe. We have tried to determine the location of possible allergenic activity on the 17kDa protein of Japanese birch pollen (Betura Platyphylla var. Japonica). In this study, we have examined the lymphocytes proliferative response (LPR) for trypsin digested materials of a 17kDa protein obtained from Betura Platyphylla var. Japonica. The strong response of lymphocyte was observed against the peptide fragments composed of amino acids from 22nd to 33rd (22-33) and from 56th to 66th (56-66) of the Bet vI molecule. It was also found that our 17kDa protein had isoleusine substitution for phenylalanine at position 31. By using synthetic peptides, we showed that asparagine at position 29 of 22-33 and glutamic acid at position 61 of 56-66 were critical for LPR. PMID- 7868056 TI - [Polysomnographic study in epilepsy with nocturnal seizures]. AB - Polysomnography was performed in 26 patients with nocturnal seizures to investigate the relationship between sleep stage and epileptic discharges and the sleep characteristics. We found three different patterns in interictal discharges (IID): Pattern A is characterized by an increase frequency of IID during slow wave sleep and a decrease of IID during REM (rapid eye movement) sleep, Pattern B is characterized by an increase of IID during stages 1 and REM, and Pattern C showed no definite correlation of IID with sleep stages. In almost all of the patients with pattern A, IID were localized to the temporal regions, whereas IID were found in the frontal or central regions in patients with patterns B and C. Further, patients with pattern A had seizures which usually occurred during the first half of the night in contrast to patients with patterns B and C, whose seizures usually occurred soon after falling asleep and/or early in the morning. Ictal discharges (ID) were observed in 18 patients. Again, there were three patterns found, :In group a, ID occurred only in NREM (non-rapid eye movement) sleep, in group b, ID occurred during NREM and REM sleep, and in group c, ID clustered in shallow, NREM sleep. In patients in group a, ID occurred from the temporal regions. In almost all of the patients in groups b and c, ID occurred from the frontal regions. Compared to normal controls, the patients with and without seizures exhibited a significant increase of stage W on polysomnography. These results suggest a relationship between the location of IID and ID and the sleep stage of expression of these discharges. The results also indicate that polygraphic sleep alterations are seen in epileptic patients. PMID- 7868057 TI - [Colony formation of mouse primitive hemopoietic progenitors with interleukin-6 and phorbol ester, and their signal transduction]. AB - Colony formation of mouse primitive hemopoietic progenitors with interleukin-6 (IL-6) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and their signal transduction were studied. Although IL-6 or TPA alone could not form colonies, their combination gave rise to significant number of colonies from Day-2 post 5 FU bone marrow cells. When colony numbers were compared with those supported by IL-3, IL-6+TPA gave rise to 86 + 47% of colonies formed with IL-3. Time course of colony formation with IL-6+TPA run parallel with that of IL-3. These colonies included not only granulocyte/macrophage (GM) colonies, but also granulocyte/erythrocyte/macrophage/megakaryocyte (GEMM) colonies and blast cell colonies. Delayed addition of IL-6 or TPA decreased colony numbers, suggesting that both IL-6 and TPA were needed from the start of cultures for maximal colony formation. When cultures were started with TPA, and IL-6 was added on Day 2 of culture or later, few colonies developed. These data suggested that IL-6 might be essential to the survival of the progenitors in culture. Chronic exposure of progenitors to TPA prior to the culture with IL-6+TPA suppressed colony formation. Addition of calphostin C, a specific protein kinase C (PKC) inhibitor or genistein and herbimycin A, specific tyrosine kinase (TK) inhibitors to the culture also decreased colony numbers formed with IL-6 and TPA. To clarify which effects of IL-6 or TPA on colony formation were blocked by the inhibitors, the inhibitors were added to preincubation of progenitors with IL-6. Both the PKC inhibitor and TK inhibitors blocked the increase of colonies resulted from a pre incubation with IL-6. Although delayed addition of TPA enhanced IL-6-dependent colony formation, delayed addition of TPA with either the PKC inhibitor or TK inhibitors canceled the increase of colonies. These data suggested that both signals of IL-6 and TPA might be transduced via activation of PKC and TK, but further studies are needed to confirm that. PMID- 7868058 TI - Allogeneic bone marrow transplantation as a therapeutic modality for hematological disorders: a report based on 39 cases. AB - The outcomes of 39 patients with hematological disorders who had undergone allogeneic bone marrow transplantation (BMT) from September 1986 to March 1992 were reported. The length of follow-up was six to 50 months. Twenty patients with acute leukemia, eight patients with aplastic anemia, seven patients with chronic myelogenous leukemia, two patients with non-Hodgkin's lymphoma, and two patients with myelodysplastic syndrome were included. Major complications were acute graft versus-host disease (GVHD) (17 cases out of 36 evaluable cases; 47 percent), chronic GVHD (13/25; 52 percent), sepsis (20/41; 49 percent), interstitial pneumonitis (IP) (10/30; 33 percent), and veno-occlusive disease (VOD) of the liver (5/41; 12 percent). Acute and chronic GVHD were well managed with cyclosporin, methotrexate, and steroids. VOD of the liver seemed to be associated with the pretransplant regimen including busulfan and cyclophosphamide. The overall probability of disease free survival of 39 patients who had undergone allogeneic BMT was 0.56. This includes nine high risk cases such as HLA antigen mismatch between the donor and the recipient, and as in the second or subsequent remission or in relapsed cases. The probability of disease free survival in patients with acute leukemia, chronic myelogenous leukemia, and aplastic anemia including high risk cases was 0.55 (n = 20), 0.71 (n = 7), and 0.50 (n = 8) respectively. These results indicate that allogeneic BMT is the major therapeutic strategy for patients whose survival could not be expected by conventional chemotherapy and that drug intensification for conditioning regimen is also important. PMID- 7868059 TI - [Roles of tyrosine phosphorylation in the proliferation of leukemic hematopoietic stem cells--analysis using a tyrosine phosphatase inhibitor]. AB - I investigated the effects of a tyrosine phosphatase inhibitor, orthovanadate, on the proliferation of normal and CML hematopoietic progenitor cells stimulated by different colony stimulating factors. Orthovanadate decreased CFU-GM colony formation from normal bone marrow cells stimulated by IL-3 and GM-CSF in a dose dependent manner, except for G-CSF. But, BFU-E colony formation was not affected by the treatment with orthovanadate. In CML cells, CFU-GM colony formation was relatively more resistant to orthovanadate than that in normal bone marrow cells and orthovanadate, surprisingly, increased BFU-E colony formation. Western blot analysis showed that preincubation of CML cells with orthovanadate resulted in the enhancement of tyrosine-phosphorylation of p65 mainly, when stimulated with EPO. These results suggest that the second messenger system of IL-3, G-CSF, GM CSF, and EPO in progenitor cells in CML is different from that in normal progenitor cells and that there is big difference in the second messenger system between myeloid and erythroid progenitor cells in CML cells. PMID- 7868060 TI - [Involvement of ICAM-1/LFA-1 adhesion molecule set in rat orthotopic liver transplantation]. AB - The distribution of ICAM-1/LFA-1-positive cells in rat liver grafts was investigated. The effect on graft survival of graft perfusion with anti-ICAM-1 monoclonal antibody before transplantation was also examined. Using ACI (RT-1av1) and LEW (RT-1(1)) inbred rats, orthotopic liver transplantation was performed both in allogeneic (ACI to LEW) and syngeneic (ACI to ACI) combinations. Transplanted liver tissues on days 2, 4 and 7 were immunohistochemically stained, using mouse anti-rat ICAM-1 monoclonal antibody (1A29, IgG1) and mouse anti-rat LFA-1 monoclonal antibody (WT-1, IgG2a). ACI livers perfused via portal vein with either 1A29, control antibody or lactate-Ringer's solution were transplanted to LEW recipients. ICAM-1 expression in normal ACI livers was confined to the endothelium of large portal vein and some central veins. A weak ICAM-1 expression was also observed on some sinusoidal endothelium. A small number of LFA-1 positive cells were resided in the normal liver. In allografted ACI livers, an intense ICAM-1 expression was induced on sinusoidal endothelium within 2 days after transplantation, and its expression was further increased on days 4 and 7. ICAM-1 expression on hepatocytes was also induced. LFA-1 positive infiltrates were gradually increased in number during the course of rejection, especially in the sinusoidal area. In the syngeneic combination, only a slight ICAM-1 induction on sinusoidal endothelium was observed. ICAM-1 upregulation on target structures of liver graft rejection suggests the importance of ICAM-1/LFA-1 in the pathogenesis of allograft rejection. Liver grafts perfused with anti-ICAM-1 monoclonal antibody were destroyed more rapidly than those perfused with control antibody or lactate-Ringer's solution both in allogeneic and syngeneic combinations. Histological examination revealed spotty ischemic necrosis in grafted liver. Perfusion with the antibody might cause the circulatory disturbance probably through the mechanism differing from alloantigen-specific response. PMID- 7868061 TI - [Immunoreactivities and messenger RNA expression of aldolase A and B in human hepatoma cell lines]. AB - Subunit specific radioimmunoassay for aldolase isozymes were developed for the quantification of human aldolase A and B. Aldolase B immunoreactivities were predominantly high in adult normal liver, while aldolase A was distinctly low. Aldolase A was high, while aldolase B was low in neonatal liver compared with the adult liver. Aldolase A immunoreactivities were almost the same as those of aldolase B in fetal liver (28 weeks). Aldolase A was predominantly found in human hepatoma tissues, whereas aldolase B was distinctly low in the same hepatoma tissues. With regard to human hepatoma cell lines, aldolase A was also predominantly found in HepG2 and PLC/PRF/5 cell lines, whereas aldolase B levels were extremely low. Almost the same results were obtained from mRNA expression of aldolase A and B in human hepatoma cell lines by the method of northern hybridization. Effects of various reagents on differentiation of hepatoma cell lines were investigated. Neither Dimethyl Sulfoxide (DMSO) and 12-O Tetradecanoylphorbol-13-acetate (TPA), which are known to be the inducers of differentiation of human leukemia cell lines such as HL-60, nor Transforming Growth Factor-beta 1 (TGF-beta 1) and Hepatocyte Growth Factor (HGF), which are known to be growth inhibitors, could cause the differentiation of hepatoma cell lines in the alteration of aldolase isozymes. The same data were shown in mRNA expression of aldolase isozymes. These results suggest that aldolase A immunoreactivities and mRNA expression are both predominantly high in hepatoma cell lines, and the reagents such as DMSO, TPA, TGF-beta 1 and HGF which tried to differentiate the hepatoma cell lines used in this study were not effective in the alteration of aldolase isozymes. PMID- 7868062 TI - [The relationship between RBC ferritin content in chronic liver diseases and iron deposition in hepatocytes]. AB - The erythrocyte (RBC) ferritin content was measured in patients with chronic liver diseases including alcoholic liver disease, liver cirrhosis (LC) and hepatocellular carcinoma (HCC), and normal subjects as controls. The relationship between RBC ferritin content and iron deposition in hepatocytes was studied. The mean RBC ferritin content (MV +/- 1SD) from normal subjects was 20.7 +/- 9.7 ag/cell in male, 11.1 +/- 5.5 ag/cell in female (ag = 10(-18)g). RBC ferritin content from chronic liver disease was higher than that of normal subjects, especially in liver cirrhosis. It elevated to 71.0 +/- 52.2 ag/cell in male, and 41.6 +/- 35.0 ag/cell in female. The iron deposition in hepatocyte was observed mostly in patients with RBC ferritin content over 20 ag/cell. The microheterogeneities of RBC ferritin from liver cirrhosis was examined by isoelectric focusing (IEF) and compared with that of normal subjects. RBC ferritin from normal subjects was detected at pI range from 5.1 to 5.7 in most cases, while it was detected at pI range from about 5.0 to 6.0 in the liver cirrhosis. More basic ferritin was detected in the latter and the peaks of pI was also more basic than that of normal controls. Since patients with liver cirrhosis examined had iron deposition in hepatocytes, it is conceivable that the occurrence of basic ferritin reflects iron overload in the liver. Taking these results together, it was concluded that the presence of iron deposition in hepatocytes and the degree of iron overload can be assumed from the determination of RBC ferritin content, a noninvasive procedure. PMID- 7868063 TI - [Aberrations of tumor suppressor genes in hepatocellular carcinomas]. AB - Mutation of the p53 gene and loss of heterozygosity of the p53, Rb, APC, and MCC genes were examined in 14 hepatocellular carcinomas (HCCs) diagnosed at the third department of internal medicine in Asahikawa Medical College. Mutations in the p53 gene were detected in 4 HCCs out of 14 (25%) using polymerase chain reaction single strand conformational polymorphism. The sites of the mutations showed a random distribution from exon 6 to 8. No mutation was observed at codon 249, which has been considered as a mutational hot spot caused by aflatoxin B1. All of the mutations occurred at a G:C base pair site, while two mutations were C:G to T:A transitions and other two mutations were G:C to T:A transversions. Pathological examination showed that the 14 HCCs consisted of 7 moderately and 7 poorly differentiated HCCs. All of the 4 HCCs which showed mutations were poorly differentiated and the frequency of the mutations were 0% in moderately and 57% in poorly differentiated HCCs. Loss of heterozygosity of the p53, Rb and APC genes were examined in the 14 HCCs using restriction fragment length polymorphism analysis. Frequencies of the loss of the p53, Rb, APC, and MCC genes were 2 out of 7 informative cases (2/7), 1/6, 0/4, and 0/7, respectively. Frequency of loss of the p53 gene in four HCCs carrying a mutated p53 gene was 1/3. These data suggest that inactivation of the p53 gene is involved in human hepatocarcinogenesis, but the APC/MCC genes are not. PMID- 7868064 TI - [Establishment of Chinese hamster ovary cell lines with reduced expression of glutathione reductase after antisense-oriented gene transfection and assessment of the sensitivity to oxidant injury]. AB - Glutathione reductase (GR) protects tissues from oxidant injury by catalysing the reduction of glutathione disulfide (GSSG) to glutathione (GSH). In order to study the effect of GR in protecting cells from oxidant injury, we generated Chinese hamster ovary (CHO) cell lines stably transformed after antisense-oriented gene transfection. The coding region of the human GR was cloned using revere transcription PCR method and selected by transient expression study in mammalian cells. A clone HGR135 showed overexpression of GR in CHO cells and was proved to have no base substitution. This clone, then, was ligated into MEP4 expression vector in an antisense orientation to the human metallothionein promoter and transfected to CHO cells with polybrene. Among 12 cell lines isolated, G17 showed to have the least GR activity (48% of the control), while another four were mildly GR deficient. Southern hybridization of genomic DNA digests and transformation experiment on E. coli revealed that the promoter-antisense coding region component was integrated. Northern hybridization detected reduced amount of GR transcript but no antisense message. Baseline cellular GSH concentrations were lower in G17 than in control (25.7 +/- 2.5 vs. 36.1 +/- 1.9 nmole/mg protein, P < 0.05), while cellular GSSG concentrations were higher (0.61 +/- 0.19 vs. 0.39 +/- 0.09 nmole/mg protein, P < 0.05). After four hours of treatment of G17 and control cells with increasing doses (1 to 10 mM) of t-butylhydroperoxide (t-BuOOH), cellular GSH concentrations in G17 decreased with an elevation of GSSG concentration at 1 mM followed by no further increase at higher t-BuOOH concentration, while GSSG concentrations increased in the control cells without reduction of GSH concentrations at 1-5 mM t-BuOOH treatment. The concentrations of GSH were lower in G17 than in controls at all doses of t-BuOOH. Four hours of exposure to 10 mM t-BuOOH resulted in greater LDH release in G17 than in control (57.3 +/- 4.7 vs. 32.1 +/- 6.5%, P < 0.05). Similarly, G17 cells released more of their LDH to the media than did CHO cells in response to exposure to 95% O2 for 72 hours (19.3 +/- 5.9 vs. 11.9 +/- 5.4%, P < 0.05). The partial GR deficiency in G17 cells impairs their ability to recycle GSSG and this deficiency offers the best explanation for the increased sensitivity of these cells to injury by t BuOOH or hyperoxia. PMID- 7868065 TI - The 5th hGH Symposium. Paris, April 7-10, 1994. PMID- 7868066 TI - Circulating growth hormone binding proteins. AB - The 'high-affinity' growth hormone binding protein (GHBP) corresponds to the extracellular domain of the membrane-associated GH receptor. In man, it is produced by proteolytic cleavage of the extracellular portion of the receptor, while in the rat and mouse, it is the product of alternative splicing of GH receptor mRNA. Because of the relationship between the GHBP and the GH receptor, measurement of serum concentrations of GHBP provide an index of GH receptor concentrations and/or affinity. PMID- 7868067 TI - The GH receptor and signal transduction. AB - The primary structure of the growth hormone (GH) receptor in rabbits and humans determined by complementary DNA cloning revealed a single membrane-spanning protein of approximately 620 amino acids. A binding protein (bp) specific for GH has been identified in the serum of a number of species. In rabbits and man, a single 4.5-kb transcript has been identified that encodes the full-length receptor. In rats and mice, however, a smaller transcript produced by alternative splicing has been reported which is specific for the GHbp. Recently, the X-ray crystallographic structure of GH and its receptor have clearly shown the formation of an unusual homodimer, consisting of one molecule of GH and two molecules of hGHbp. Formation of the GH dimer is a necessary prerequisite for biological activity. The transcriptional activity of wild-type and mutant forms of GH receptor has been determined by co-transfecting the promoter of a GH responsive gene, coupled to CAT along with the receptor cDNA. A 25-amino acid region near the transmembrane domain has been shown to be important for functional activity, although 8 amino acids (known as Box 1), rich in prolines, is essential. Alanine scanning mutagenesis has revealed that individual substitution of each residue is without effect, while the replacement of the last 2 or all 4 of the prolines abolishes activity. Finally, GH has been shown to induce rapid tyrosine phosphorylation of several proteins in cells expressing the receptor, one of which has recently been identified as the kinase JAK2 and another as MAP kinase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868068 TI - The insulin-like growth factor-I receptor. Structure, ligand-binding mechanism and signal transduction. AB - The nonclassical binding kinetics of IGF-I and insulin to their respective receptors, suggestive of negative cooperativity, can be readily explained by our recently proposed novel binding mechanism whereby the bivalent ligand bridges the two receptor alpha-subunits alternatively at opposite sites in a symmetrical receptor structure. The bivalent binding mechanism also explains bell-shaped bioactivity curves. The possible role of different binding modes versus differences in downstream signaling by insulin and IGF-I in producing specific mitogenic or metabolic responses is discussed. PMID- 7868069 TI - Rapid nuclear actions of growth hormone. AB - The mechanisms by which growth hormone (GH) initiates its effect on growth are largely unknown. In this report we examine the acute actions of GH with a focus on the intracellular signaling pathways leading from the cell-surface GH receptor into the nucleus, and culminating in the activation of specific target genes. We show that in vivo GH treatment leads to the rapid appearance of tyrosine phosphorylated nuclear proteins and the equally rapid induction of c-fos and insulin-like growth factor I gene transcription. A model is proposed for a GH activated intracellular signal transduction pathway. PMID- 7868070 TI - Parental imprinting and the IGF2 gene. AB - The phenomenon of parental imprinting has become increasingly important in disciplines such as evolution, genetics, molecular biology, embryology and pathology. Principally, parental imprinting refers to a parent-of-origin dependent expression of a subset of autosomal loci, independent of the sex of the offspring. Today, at least seven such loci have been identified, including the human IGF2 gene. It appears that the set of imprinted genes is not always identical between the species, although the importance of maintaining this kind of gene regulation is evolutionarily conserved. It is particularly interesting from the clinical point of view that a number of human diseases, such as the Beckwith-Wiedemann and Prader-Willi/Angelman syndromes, appear to involve unbalanced parental contributions of imprinted loci. We show here that the four different human IGF2 promoters are expressed mono- and/or biallelically in complex patterns in postnatal liver specimens. PMID- 7868072 TI - Molecular basis of familial growth hormone deficiency. AB - A significant proportion of cases of GH deficiency (5-30%) may be due to genetic causes. At least four Mendelian types of isolated GH deficiency (IGHD) have been delineated based on the mode of inheritance and the degree of GH deficiency: IGHD type IA, autosomal recessive with absent endogenous GH; type IB, autosomal recessive with diminished GH; type II, autosomal dominant with diminished GH; and type III, X-linked with diminished GH. Most patients with IGHD type IA have heterogeneous deletions, ranging in size from 6.7 kb to 45 kb, that encompass the entire gene encoding for pituitary GH, GH-1. Nonsense, frameshift and splice GH-1 mutations that predict a complete lack of bioactive GH synthesis in homozygotes have also been reported in association with IGHD IA. Additionally, some cases of IGHD type II have dominant negative mutations in one allele of the GH-1 gene. Panhypopituitary Dwarfism (PD), a condition characterized by deficiency of at least other pituitary trophic hormone in addition to GH deficiency, can have autosomal and X-linked modes of inheritance. Interestingly, both recessive and dominant mutations at the gene encoding for the pituitary transcription factor Pit-1 have been found in a specific subtype of PD that combines GH, prolactin and TSH deficiencies. In contrast, the loci and mutations responsible for the other Mendelian forms of IGHD and PD remain unknown. Linkage studies using genetic markers have excluded the GH locus on chromosome 20 in all the studied families (types IB and II) in whom the mutation cannot be traced to defects in these genes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868071 TI - Molecular genetics of growth hormone-releasing factors. AB - To elucidate the effects of GRF on GH synthesis and of the GH-IGF-I axis on hypothalamic GRF synthesis, we measured the mRNA levels of hypothalamic GRF and pituitary GH in pubertal male rats treated for 3 weeks with antirat GRF gamma globulin (GRF-ab), antisomatostatin gamma-globulin (SRIF-ab) or both. Immunoneutralization of circulating endogenous GRF resulted in a marked decrease in serum IGF-I and pituitary GH mRNA levels in Northern blot analysis, whereas it significantly increased GRF mRNA levels in the arcuate nucleus in both Northern blot and in situ hybridization analysis. Immunoneutralization of circulating endogenous SRIF failed to affect GRF mRNA levels but caused a slight reduction in pituitary GH mRNA. Then, we examined the effect of systemic replacement with rat GH or IGF-I for 1 week on GRF mRNA levels in the hypothalamus of rats treated with GRF-ab for 2 weeks. Replacement with either rat GH or IGF-I significantly suppressed the increased hypothalamic GRF mRNA levels. These data indicate that endogenous GRF is essential in normal synthesis of pituitary GH and that both GH and IGF-I negatively regulate the synthesis of hypothalamic GRF. PMID- 7868073 TI - Laron syndrome: clinical features, molecular pathology and treatment. AB - Primary growth hormone (GH) insensitivity (Laron syndrome) is a hereditary disease due to polymorphic defects in the GH receptor, or in the postreceptor mechanisms, leading to an inability to generate IGF-1. The clinical features and biochemical profiles are indistinguishable from isolated GH deficiency. A diagnostic feature is the lack of rise of serum IGF-1 in response to GH. In most patients growth hormone binding protein is low. Treatment of children with Laron syndrome by biosynthetic IGF-1 accelerates linear growth velocity and head circumference, reduces body fat, and stimulates kidney function. PMID- 7868074 TI - Regulation of intrauterine growth: the role of maternal health. AB - Plasma substrate regulation is outlined in healthy mothers and compared with changes observed in diabetes. Placental exchange of glucose, amino acids and lipids are briefly outlined and regulation by maternal and placental hormones discussed. Fetal adaptation to excess and reduced nutrient supply are shown and fetal hormonal responses described. Examples of how maternal health can affect the offspring in postnatal life are given. PMID- 7868075 TI - Hormonal regulation of fetal growth. AB - The regulation of fetal growth is complex and poorly known. During the first trimester of pregnancy, no strict endocrine mechanisms are involved, but embryonic growth might be controlled at the level of the individual organs by supply of nutrients and by locally active growth factors. Later on, fetal growth depends essentially upon the maternoplacental cooperation in delivering nutrients to the fetus. Therefore, the major role of hormones in fetal growth is to mediate the utilization of available substrate. In late gestation, placental size and fetal growth rate are well correlated, pointing to a key role of the placenta in the regulation of fetal growth. It is therefore important to understand the molecular mechanisms involved in regulating placental development and endocrine functions. TGF alpha and EGF might play major roles as suggested by the modulation of their receptors with placental development, and by the specific alterations of EGF receptors in intrauterine growth retardation. In addition, human placenta specifically secretes placental growth hormone, the level of which is significantly decreased in the sera of pregnant women bearing a fetus with intrauterine growth retardation. PMID- 7868076 TI - Placental transport of nutrients to the fetus. AB - The exchange of nutrients between placenta and fetus involves three major mechanisms: (1) direct placental transfer of nutrients from the maternal to the fetal plasma; (2) placental metabolism and consumption of nutrients; (3) placental metabolism of nutrient substrates to alternate substrate forms. Carbohydrate is transported to the fetus as glucose which is taken up from the maternal plasma by the GLUT 1 transporter and transported to the fetus by facilitative diffusion according to concentration-dependent kinetics. Protein is transported to the fetus as amino acids by specific amino acid transporter proteins. Placental lipid transport to the fetus involves direct transporter mediated transfer of certain fatty acids as well as lipid uptake from lipoproteins, metabolic alteration in the placenta, and release into the fetal plasma. Placental size, architecture, developmental and pathological processes, and interaction with the fetus cooperate with transport and metabolic mechanisms to affect placental-fetal nutrient exchange. PMID- 7868077 TI - Outcome of low birthweight. AB - Babies who are small at birth and during infancy are now known to be at an increased risk of developing coronary heart disease, hypertension and diabetes during adult life. This has led to the suggestion that these diseases are 'programmed' by an inadequate supply of nutrients or oxygen in utero or immediately after birth. The phenomenon of 'programming', whereby undernutrition in early life permanently changes body structure and function, is well documented in animals. As yet we know little about cellular and molecular changes which underlie it, but persisting changes in the secretion of hormones or in the sensitivity of tissues to them may be important in determining adult disease. PMID- 7868078 TI - Progress report: growth hormone in skeletal dysplasia. AB - Growth hormone is not a logical treatment for the short stature associated with skeletal dysplasia because growth hormone concentrations are normal in these individuals. Short-term trials of growth hormone have demonstrated an increase in growth velocity in most of the skeletal dysplasias. Only in the skeletal dysplasia associated with Turner syndrome do we have data confirming that growth hormone treatment results in an increase in final height. Studies in achondroplasia and hypochondroplasia have demonstrated an increase in growth velocity which has been sustained for up to 4 and 6 years, respectively. In the long term, increased knowledge of the defects involved in skeletal dysplasia may lead us to improvements in both diagnosis and treatment. PMID- 7868079 TI - Adult growth hormone deficiency. AB - Several reports have focused on the clinical features of the untreated GH deficient adult and the effect of GH therapy. The results reported are strikingly unanimous. Untreated GH-deficient adults have been shown to have increased cardiovascular mortality, reduced exercise capacity, reduced muscle strength, subnormal glomerular filtration rate and renal plasma flow, defective sweat secretion and defective thermoregulation, reduced energy expenditure and basal metabolic rate, abnormal thyroid hormone metabolism, reduced myocardial function and clinical signs of premature atherosclerosis. Body composition has been found abnormal with increased fat mass, decreased lean body mass, decreased muscle fat ratio, visceral obesity, reduced extracellular fluid volume and reduced bone mineral content. Furthermore, two independent groups have reported impaired psychological wellbeing as compared to normal subjects. Apart from the observation on total mortality, all the above-reported abnormalities improve during GH substitution. The only recognisable side effects so far has been fluid retention, which is usually transient and dose-dependent. It is concluded that GH deficiency has distinct clinical consequences all of which can be totally or partially alleviated by GH replacement therapy. PMID- 7868080 TI - Amyloidosis. AB - Amyloidosis is a heterogeneous group of disorders characterized by extracellular deposition of abnormal protein fibrils which are derived from different proteins in different forms of the disease. Asymptomatic amyloid deposition in a variety of tissues is a universal accompaniment of ageing, and clinical amyloidosis is not rare. Intracerebral and cerebrovascular beta-protein amyloid deposits are a hallmark of the pathology of both sporadic and familial Alzheimer's disease, beta 2-microglobulin-derived amyloid is a common complication of long term haemodialysis, and islet amyloid polypeptide is the fibril protein in the universal islet amyloidosis of type II diabetes mellitus. New fibril proteins have lately been identified in hereditary amyloidosis, including variants of gelsolin, apolipoprotein AI, lysozyme and fibrinogen. The development of radiolabelled serum amyloid P component (SAP) scintigraphy has allowed amyloid to be diagnosed non-invasively in vivo for the first time, provided unique insight into the distribution and size of amyloid deposits, and yielded novel information on the natural history and the effects of treatment. Amyloid deposits are in a state of dynamic turnover and can regress if new fibril formation is halted. The recent elucidation of the three dimensional structure of human SAP may enable the design of specific therapeutic agents. PMID- 7868081 TI - Intervertebral disc amyloidosis: histochemical, immunohistochemical and ultrastructural observations. AB - Intervertebral discs selected at random from autopsies and surgical operations on herniated discs were examined for evidence of amyloid deposition. Amyloid deposits were detected in 53 (81.5%) of 65 autopsy cases. Discs from subjects over 50 years of age revealed a significantly high incidence of amyloid deposition. Among herniated discs, amyloid deposits were documented in 49 (75.4%) of 65 surgical specimens. The incidence of amyloid deposition in intervertebral discs increased with advancing age. Intervertebral disc amyloidosis consisted of amyloid deposits of three morphological types: linear amyloid deposits around the degenerating chondrocytes (perichondrocyte type), and nodular or band-like deposits in the annulus fibrosus (annulus fibrosus type) and nucleus pulposus (nucleus pulposus type). We suspect that the precursor protein of perichondrocyte type amyloid is derived from chondrocytes, and those of annulus fibrosus type and nucleus pulposus types are derived from the blood. The amyloid deposits were resistant to treatment with potassium permanganate. Immunohistochemically, the amyloid deposits reacted with antibody against amyloid P-component, but not with antibodies against AA, A kappa, A lambda, transthyretin or beta 2-microglobulin. Ultrastructurally, the amyloid deposits were composed of 10 nm-wide nonbranching fibrils. The amyloid in herniated discs had the same biochemical and immunohistochemical properties as those found in autopsy cases. The immunohistochemical characteristics of the amyloid deposits suggest that it derives from an, as yet, unknown precursor protein. PMID- 7868082 TI - Cutaneous epithelioid angiosarcoma: a clinicopathological study of four cases. AB - Four cases of cutaneous epithelioid angiosarcoma are described together with the potential diagnostic trap of mistaking these tumours for poorly differentiated carcinoma or malignant melanoma. The immunophenotypic profile using four endothelial markers showed positive staining in all cases for factor VIII related antigen in a predominantly paranuclear dot-like fashion and for CD31 (JC70); in three cases for CD34 (QB-END/10) and in two cases with UEA-1. All four cases were cytokeratin (CAM 5.2 and AE1/AE3) negative in contrast to the positive staining reported at non-cutaneous sites. Aberrant S-100 protein expression was seen in one case. In two cases subsequent recurrences showed better differentiation than the original tumour. Electronmicroscopy confirmed the absence of non-endothelial lines of differentiation but failed to reveal Weibel-Palade bodies. PMID- 7868083 TI - Differentiation of adenocarcinoma of the lung and malignant mesothelioma: predictive value and reproducibility of immunoreactive antibodies. AB - A panel of antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen (Ber-EP4), carcinoembryonic antigen (CEA), tumour-associated glycoprotein (B72.3), vimentin and LeuM1 was applied to sections of adenocarcinoma of the lung and malignant mesothelioma in a randomized design. The proportion of stained tumour cells within each section was estimated independently in five categories by three pathologists (no positive tumour cells, 1-10%, 11-33%, 34-66% and more than 67% positive tumour cells). The kappa values representing the chance corrected interobserver agreement for the different antibodies in such a five group assessment were between 0.38 and 0.72. In two group assessment the kappa values were between 0.53 and 0.94. Nosological sensitivity and nosological specificity were calculated for all antibodies, and diagnostic sensitivity and diagnostic specificity (predictive values) were calculated for the Ber-EP4, CEA, B72.3, LeuM1 and vimentin. The difference between nosological sensitivity and nosologic specificity and the clinically relevant predictive values of positive and negative tests were demonstrated. In respect of the reproducibility and the diagnostic power defined by the predictive values, we demonstrated that a panel of antibodies, including CEA, Ber-EP4 and B72.3 and, to a lesser degree, LeuM1 and vimentin is applicable for the histopathological distinction between adenocarcinoma of the lung and malignant mesotheliomas. Before introduction of new diagnostic tests, including new antibodies, the prevalence of the tested tumours should be estimated. Nosological sensitivity and nosological specificity should be converted to predictive values. PMID- 7868084 TI - Familial haemophagocytic lymphohistiocytosis. A report of three cases with unusual lung involvement. AB - Three cases of familial haemophagocytic lymphohistiocytosis are presented with lung infiltration by haemophagocytic histiocytes. In all patients the diagnosis was based on hepatosplenomegaly, thrombocytopenia and anaemia, abnormal increase in triglycerides, ferritin and LDH, hypofibrinogenaemia and lymphohistiocytosis with haemophagocytosis in bone marrow. Two patients died of respiratory failure due to interstitial pneumonia. In these two patients the pneumonia was obscured and misinterpreted by the pathologists. A careful re-examination revealed lymphohistiocytosis and haemophagocytic cells within the lung parenchyma. The third patient showed alveolar wall infiltration by haemophagocytic histiocytes and lymphocytes. In early childhood acute or recurrent interstitial pneumonia should prompt a search for haemophagocytic histiocytes, and familial haemophagocytic lymphohistiocytosis should be included in the differential diagnosis. PMID- 7868085 TI - Effects of chemotherapy on ultrastructure of oesophageal squamous cell carcinoma. AB - Seven oesophageal squamous carcinomas, treated with pre-operative chemotherapy (mitomycin-C, ifosfamide and cisplatin-MIC), with a course finishing 21 days prior to resection, were examined by electronmicroscopy. In one treated case detailed light microscopy failed to reveal any tumour. Five of the remaining six tumours showed cytotoxic damage in that apoptosis and unusual necrotic changes were observed in almost all the neoplastic cells. These features were not seen in untreated cases. In four additional cases, who received one pulse of MIC followed by biopsy or resection within 3-6 days, apoptotic changes were very pronounced and extensive and most neoplastic cells presented unusual degeneration with characteristic derangement of the cytoskeleton, destruction of organelles and accumulation of glycogen. The ultrastructural appearance of 18 untreated resected oesophageal squamous carcinomas was studied for comparison with the treated tumours. The study has demonstrated ultrastructural changes resulting from chemotherapy. Results suggest that the regimen is more effective against squamous carcinomas than against adenocarcinomas of the oesophagus, as judged by comparison with the results of a previous study. PMID- 7868086 TI - Cytoplasmic c-erbB-2 protein expression correlates with survival in Dukes' B colorectal carcinoma. AB - The prognostic significance of c-erbB-2 expression was studied in paraffin wax embedded colorectal cancer tissue using a monoclonal antibody. One hundred and sixty-four patients with Dukes' B disease were studied. Membranous staining was not detected in any case. Cytoplasmic c-erbB-2 staining was seen in 55 cancers (33.5%). Cytoplasmic staining was unrelated to patient age (P = 0.31), sex (P = 0.69), tumour site (P = 0.69), size (P = 0.57), histological grade (P = 0.42) or ploidy status (P = 0.21) but was found more frequently in obstructing cancers (P = 0.03). Mean follow up of the patient population was 6.3 years. Five-year survival estimated by the Kaplan-Meier life-table method was 47% for those with cytoplasmic c-erbB-2 staining and 77% for those without (log rank analysis; P < or = 0.0001). Stepwise regression analysis identified c-erbB-2 staining (relative risk, 2.51; P = 0.0005) and bowel obstruction (relative risk, 1.99; P = 0.015) as independent predictors of survival. It is suggested that cytoplasmic c-erbB-2 expression may provide a useful marker of tumour behaviour in Dukes' B colorectal cancer. PMID- 7868087 TI - Tetranectin expression in human colonic neoplasia. AB - The expression of tetranectin in colonic neoplasia was evaluated by determining the tissue distribution by immunohistological analysis of tissue sections and the antigen levels in tissue homogenates and plasma. In normal colonic mucosa tetranectin staining was predominantly found in the goblet cells whereas in adenocarcinomas this staining was confined to the tumour stroma. Colonic adenomas, benign precursors of adenocarcinomas, showed fewer tetranectin positive goblet cells and in some cases showed tetranectin expression in the stroma. Within the tissue homogenates no differences were found in the tetranectin levels between normal mucosa, adenomas and carcinomas. Patients with colonic cancer were found to have significantly decreased plasma tetranectin levels compared to healthy controls. Thus, colonic neoplasia is associated with a change in the tissue distribution of tetranectin, without an obvious change in the tissue level, and a low plasma tetranectin level. PMID- 7868088 TI - Mesothelial cell inclusions within mediastinal lymph nodes. AB - The presence of mesothelial cell inclusions within mediastinal lymph nodes is an extremely rare occurrence with apparently only two previously reported cases. We report a single case with immunohistochemistry and transmission electron microscopy. A study of 318 mediastinal nodes from 80 patients using haematoxylin and eosin and immunohistochemistry is reported with the observation of no further positive cases. A review of the literature concerning nodal inclusions found at other anatomical sites aids discussion on the aetiology of this type of nodal inclusion. PMID- 7868089 TI - Hepatic lesions induced by Angiostrongylus costaricensis. PMID- 7868090 TI - Cutaneous ciliated cyst occurring in a male. PMID- 7868091 TI - Epithelial-myoepithelial carcinoma with co-existing multifocal intercalated duct hyperplasia of the parotid gland. PMID- 7868092 TI - Ameloblastoma with stromal multinucleated giant cells. AB - We report a case of ameloblastoma which uniquely showed heavy osteoclast-like giant cell accumulation and woven bone formation in the surrounding fibrous stroma. Immunohistochemistry showed that the giant cells were non-epithelial in origin and suggested that stromal factors (i.e., the presence or absence of mineralized bone) determines whether these cells express an osteoclastic antigenic phenotype. PMID- 7868093 TI - Epstein-Barr virus and T-cell lymphoma. PMID- 7868095 TI - Aphthoid ulceration in diversion colitis. PMID- 7868094 TI - Epithelioid angiosarcoma of the gallbladder. PMID- 7868096 TI - Outcomes assessment and psychiatric services. Committee on Psychopathology, Group for the Advancement of Psychiatry. PMID- 7868097 TI - Definitive treatment of patients with serious mental disorders in an emergency service, Part II. PMID- 7868099 TI - Changing roles of mental health clinicians in multidisciplinary teams. PMID- 7868098 TI - Rehabilitation psychiatry in the inpatient treatment of a woman with paranoid schizophrenia. PMID- 7868100 TI - Prevention of recurrent postpartum major depression. AB - OBJECTIVE: Postpartum depression affects between 10 and 15 percent of new mothers. These mothers are apprehensive about recurrence after later births. This study tested the efficacy of antidepressant medication administered during the postpartum period to prevent a recurrence of postpartum depression among women who had suffered a previous episode. METHODS: An open clinical trial was conducted at a university-based outpatient clinic treating pregnant and postpartum women with mood disorders. Study participants were 23 pregnant women who had at least one previous postpartum episode that fit DSM-III-R criteria for nonbipolar major depression without psychotic features. Postpartum monitoring for recurrence of depressive symptoms was compared with postpartum monitoring plus postbirth treatment with either the medication that had been effective for the previous episode or nortriptyline. The first dose was given within 24 hours of birth. The authors assessed recurrence of postpartum major depression by psychiatric examination and use of the Inventory to Diagnose Depression, a reliable self-report instrument. RESULTS: A significantly greater proportion of the women who elected monitoring alone (62.5 percent) suffered recurrence of major depression compared with the women who received monitoring plus medication (6.7 percent) (p = .0086). CONCLUSIONS: Prophylactic antidepressant treatment reduced the recurrence of postpartum major depression. PMID- 7868101 TI - Clinical and treatment correlates of access to Section 8 certificates for homeless mentally ill persons. AB - OBJECTIVE: The study assessed how clients' housing preference and other variables were related to the acquisition of Section 8 certificates, facilitating independent living, for homeless persons with severe mental illness who were being served by an experimental assertive community treatment team. METHODS: For 77 clients, demographic and clinical differences between receivers and nonreceivers of certificates were examined, and correlates of time from referral to the team to completion of the Section 8 application were analyzed. Reasons clients did not receive certificates and housing outcomes were summarized in relation to client preference. RESULTS: The 34 clients who received certificates (44 percent) had significantly less psychopathology after three months than did nonreceivers and tended to have affective disorders rather than schizophrenia. Of the 43 nonreceivers, the two largest groups were 19 clients who did not want certificates and ten clients who wanted certificates but whom staff considered unable to live safely in an unsupervised apartment. The mean +/- SD length of time for application for a certificate was 5.7 +/- 5.8 months. Longer time to apply was significantly associated with having schizophrenia, having the team as a representative payee, and showing increased psychotic symptoms at referral and at three months. CONCLUSIONS: The study suggests that it is possible to honor the housing preferences of the majority of homeless persons with severe mental illness if adequate resources are provided. However, staff may view persons who have schizophrenia and more symptoms as needing more supervision than those clients prefer. Homeless mentally ill persons may also take longer than more symptomatic persons to pursue independent living through a Section 8 certificate. PMID- 7868103 TI - Opportunities for psychiatrists in managed care organizations. AB - Managed care organizations have used psychiatrists primarily for their patient care skills, and their potential for performing administrative and managerial services for managed care organizations has not been fully appreciated. However, the role of physician managers is likely to expand with or without federal action on health care reform. Areas of opportunity for psychiatrists include utilization and quality management, network development, provider profiling, and credentialing. In addition, psychiatrists may serve as ombudsmen for managed care organizations and support internal operations. Although formal training beyond medical school and residency is not necessary for psychiatrists to become effective managers, various educational programs are available and are highly recommended. PMID- 7868102 TI - Characteristics of private-sector managed care for mental health and substance abuse treatment. AB - OBJECTIVE: This study examined diversity during the late 1980s in managed care programs for mental health, alcohol abuse, and drug abuse to identify ways in which research can generate more meaningful data on the effectiveness of utilization review programs. METHODS: Telephone interviews were conducted with representatives of utilization review programs for employee health insurance plans in 31 firms that employed 2.1 million people in 1990. Questions addressed qualifications of personnel, clinical criteria to authorize care, integration with employee assistance plans, penalties for not complying with utilization review procedures, outpatient review, and carve out of mental health and substance abuse review. RESULTS: Large variations in utilization review programs were found. Programs employed a range of review personnel and used a variety of clinical criteria to authorize care. More than two-thirds did not carve out mental health and substance abuse review from medical-surgical review. Some firms' employee assistance plans were integrated with utilization review programs, while others remained unintegrated. Penalties for not following program procedures varied widely, as did review of outpatient services. CONCLUSIONS: Because of trends toward even more diversity in utilization review programs in the 1990s, research that identifies the specific features of managed care programs that hold most promise for controlling costs while maintaining quality of care will increasingly be needed. PMID- 7868105 TI - Borderline personality disorder from the patient's perspective. AB - OBJECTIVES: Patients with a diagnosis of borderline personality disorder were studied to learn how they experienced the disorder and its treatment. METHODS: Life history narratives were obtained from ten patients with borderline personality disorder in a series of 90-minute interviews held over the course of a year. The interviews had minimal structure; patients were simply asked to talk about themselves. RESULTS: The narratives revealed striking similarities in the patients' experience with borderline personality disorder. Reports of their experience differed markedly from clinical descriptions of the disorder. Common themes of estrangement, inadequacy, and despair were identified, as well as common coping strategies, primarily dissociation and avoidance of self disclosure. CONCLUSIONS: Patients' experiences with borderline personality disorder were highly consistent but differed markedly from clinical descriptions. The patient narratives provided information that could lead to more effective treatment of the disorder. PMID- 7868104 TI - Historical development of legal protection for the rights of mentally ill persons in France. AB - The authors trace the development of legal protection of the rights of mentally ill persons to the experiences of Gabriel-Honore de Riqueti, the Count of Mirabeau, who was imprisoned without due process more than 200 years ago. Influenced by the ideas of the leaders of the American Revolution, he later became a representative to the French Republic's National Assembly and played a pivotal role in defining human rights, including the rights of mentally ill persons, in France. He advocated involvement of judicial authorities in any decision to confine a citizen, even in the case of mental disorder. French civil commitment legislation of 1838 established the authority of physicians and civil officials in commitment decisions, but limited judicial involvement to review after commitment. A new 1990 law limits judicial involvement to review after commitment, but extends the rights of hospitalized patients in many areas. PMID- 7868106 TI - Adjunctive trazodone in the treatment of negative symptoms of schizophrenia. AB - OBJECTIVE: The study examined whether adjunctive treatment with trazodone would reduce negative symptomatology in patients with chronic, residual schizophrenia. METHODS: Patients selected for the study had an established clinical diagnosis of chronic schizophrenia with stable symptomatology, an absence of florid psychotic symptons, a stable regimen of neuroleptic medication, and an absence of depressive disorder. Active psychotic symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS) score on the thinking disturbance factor. Negative symptoms were assessed using the BPRS withdrawal retardation factor as well as the affective flattening and alogia subscales from the Scale for Assessment of Negative Symptoms. Forty-nine patients were randomly assigned to either trazodone or placebo in a six-week double-blind trial. RESULTS: Forty seven patients, 23 men and 24 women with an average age of 60 years, completed the six-week trial. Twenty-six of the patients received trazodone. Adjunctive treatment with trazodone significantly reduced the severity ratings on two of three measures of negative symptoms and did not significantly increase the severity of positive symptoms; however, the magnitude of the therapeutic effect was modest. The scores for negative symptoms were reduced by approximately 10 to 15 percent, and only three of the 26 actively treated patients showed moderate clinical improvement. CONCLUSIONS: Trazodone, used in conjunction with neuroleptics, mildly reduces the severity of negative symptoms in residual schizophrenia and does not exacerbate florid psychosis. The potential benefits of adjunctive trazodone therapy may outweigh the risk of worsening psychosis. PMID- 7868107 TI - The early case for caring for the insane in general hospitals. AB - The early argument for caring for the insane in general hospitals arose in the late 1800s in the context of criticisms of the asylum made by neurologists and some psychiatrists. The movement in support of general hospital psychiatry gained ground within psychiatry as the modernization of the general hospital made it a more attractive work site for physicians. By the second decade of this century, a newly independent discipline of hospital administration was providing an audience for psychiatrists who wanted to make the medical and financial case for the value of psychiatric care in the general hospital. Although in the 1930s only a fraction of general hospitals included a "department for mental patients," general hospital psychiatric treatment had ceased to be only a rhetorical or experimental concept and was fast becoming a practical program of treatment. PMID- 7868108 TI - Effects of alcohol on symptoms in alcoholic and nonalcoholic patients with schizophrenia. PMID- 7868109 TI - An inpatient team's response to alleged sexual misconduct by an outpatient psychotherapist. PMID- 7868110 TI - Factors related to psychiatric consultation for schizophrenic patients receiving medical care. PMID- 7868111 TI - Psychiatrists' and patients' views on drug information sources and medication compliance. PMID- 7868112 TI - Folie a deux in identical twins. PMID- 7868113 TI - How to treat inpatients. PMID- 7868114 TI - Multiple personality. PMID- 7868115 TI - Identifying chromosomal fragile sites from individuals: a multinomial statistical model. AB - The inability to identify fragile sites from data for single individuals remains the major obstacle to determining whether these chromosomal loci are predisposed to cancer-causing and evolutionary rearrangements. We describe a novel statistical model that is amenable to data from single individuals and that establishes site-specific chromosomal breakage as nonrandom with respect to the distribution of total breakage. Our method tests incrementally smaller subsets of the data for homogeneity under a multinomial model that assigns equal probabilities to a maximal set of nonfragile sites and unrestricted probabilities to the remaining fragile sites with significantly higher numbers of breaks. We show how standardized Pearson's chi-square (X2) and likelihood-ratio (G2) statistics can be appropriately used to measure goodness-of-fit for sparse contingency (individual-based) data in this model. A sample application of this approach indicates extensive variation in fragile sites among individuals and marked differences in fragile-site inferences from pooled as opposed to per individual data. PMID- 7868117 TI - Somatic expansion of the (CAG)n repeat in Huntington disease brains. AB - The mutation causing Huntington disease (HD) has been identified as an expansion of a polymorphic (CAG)n repeat in the 5' part of the huntingtin gene. The specific neuropathology of HD, viz. selective neuronal loss in the caudate nucleus and putamen, cannot be explained by the widespread expression of the gene. Since somatic expansion is observed in affected tissue in myotonic dystrophy, we have studied the length of the (CAG)n repeat in various regions of the brain. Although we have not found clear differences when comparing severely and mildly affected regions, we have observed a minor increase in repeat length upon comparison of affected brain samples with cerebellum or peripheral blood. Hence, although further somatic amplification seems to occur in affected areas of the brain, the differences between affected and unaffected regions are too small to make this mechanism an obvious candidate for the cause of differential neuronal degeneration in HD. PMID- 7868116 TI - Chromosomal localization of the human NF-E2 family of bZIP transcription factors by fluorescence in situ hybridization. AB - A family of human genes encoding basic-leucine zipper (bZIP) transcription factors, p45-NF-E2, Nrf1 and Nrf2, have been isolated independently. Whereas the encoded proteins of the three genes share highly conserved regions distinct from other bZIP families such as Jun or Fos, remaining regions diverged considerably from each other. Chromosomal localization by fluorescence in situ hybridization demonstrates that these genes are non-syntenic. p45-NF-E2 mapped to chromosome 12q13.1-13.3, whereas Nrf1 and 2 mapped to 17q21.3 and 2q31, respectively. However, these three genes were probably derived from a single ancestor by chromosomal duplication as other genes that also map in these regions are related to one another. PMID- 7868118 TI - Sequence polymorphism in kringle IV 37 in linkage disequilibrium with the apolipoprotein (a) size polymorphism. AB - Apolipoprotein(a) [apo(a)] contains a variable number of identical (K-IV A/B) or nearly identical (K-IV 1, K-IV 30-37) kringle repeats that are homologous to K-IV from plasminogen. The sizes of 414 apo(a) alleles were determined by pulsed-field gel electrophoresis (PFGE) of KpnI-digested DNA. Furthermore, sequence variation in the apo(a) K-IV 30-37 domain was analysed. Reverse transcription/polymerase chain reaction (RT-PCR) cloning of human liver poly A+ RNA followed by sequencing revealed a single nucleotide exchange in the ultimate K-IV (K-IV 37) of apo(a) (codon 4168); this results in an ATG (Met) to ACG (Thr) substitution. A PCR-based restriction assay of genomic DNA demonstrated that this substitution represents a common polymorphism. In 231 unrelated Tyroleans, the frequencies for the K-IV 37 Thr and K-IV 37 Met alleles were 0.66 and 0.34, respectively. The phase between the K-IV 37 Met/Thr and the KpnI size polymorphism was determined for 224 alleles. A significant linkage disequilibrium was detected between the sequence and size polymorphisms of apo(a). K-IV 37 Met was significantly associated with KpnI allele no. 18 (DAB = 0.0267 +/- 0.0101; chi 2 = 10.09, df = 1). The Met/Thr polymorphism was further used to test whether deletions or duplications of K-IV 37 occur frequently in the apo(a) gene. Some 40 apo(a) alleles, 22 of which were from subjects that appeared to be double heterozygotes for K-IV repeat number and the Met/Thr variation were separated by PFGE and analysed for the 4168 Met/Thr polymorphism. The Met and Thr sequences were always present on different size alleles and no evidence for a duplication or deletion of K-IV 37 was obtained. This suggests that the copy number of K-IV 37 is invariable, in contrast to the highly variable K-IV A/B domain of the gene. The 4168 Met/Thr polymorphism had no effect on Lp(a) concentration, neither did it influence the lysine-binding property of the Lp(a) particle. PMID- 7868119 TI - Deletion mapping of stature determinants on the long arm of the Y chromosome. AB - A gene contributing to human growth has previously been tentatively mapped to the long arm of the Y chromosome. In the present study, recently developed sequence tagged site markers covering the entire Y chromosome were used to define deletion breakpoints in 15 males with partial deletions of Yq. By correlating the height of these individuals with their deletion breakpoints, we located a region whose presence or absence has a marked effect on stature. This critical region comprises the most proximal portion of the long arm, extending from marker sY78 in interval 4B to marker sY94 in interval 5G of the proximal long arm. PMID- 7868120 TI - Analysis of pericentromeric chromosome 21 specific YAC clones by FISH: identification of new markers for molecular-cytogenetic application. AB - Fluorescence in situ hybridization (FISH) of chromosome 21 specific yeast artificial chromosome (YAC) clones after Alu-PCR (polymerase chain reaction) amplification has been used to find new region-specific DNA probes for the heterochromatic region of chromosome 21. Six overlapping YAC clones from a pericentromeric contig map (region 21cen-21q11) were analyzed. Four YAC clones were characterized as hybridizing to several chromosomal locations. They are, therefore, either chimeric or shared by different chromosomes. Two of them containing alphoid satellite DNA, are localized at the centromeric regions of chromosomes 13 and 21 (clone 243A11), and on 13cen, 21cen and 1q3 (clone 781G5); the two others are localized at both 21q11 and 13q2 (clone 759D3), and at 18p (clone 770B3). Two YACs were strongly specific for chromosome 21q11 only (clones 124A7 and 881D2). These YACs were used effectively as probes for identifications of chromosome 21 during metaphase and interphase analysis of 12 individuals, including three families with Down syndrome offspring, and 6 aminocyte samples. The location of YAC clones on 21q11 close to the centromeric region allows the application of these clones as molecular probes for the analysis of marker chromosomes with partial deletions of the long arm as well as for pre- and postnatal diagnosis of trisomy 21 when alphoid or more distal region-specific DNA probes are uninformative. Overlapping YAC clones covering human chromosome 21q may be systematically used to detect a set of band-specific DNA probes for molecular-cytogenetic application. PMID- 7868121 TI - Interphase cytogenetics on paraffin-embedded sections of ovary for detection of genomic constitution in a patient with Turner's syndrome and chromosomal mosaicism. AB - The difficulty of detecting sex chromosome mosaicism cytogenetically hinders the finding of an acceptable explanation for phenotypic-genotypic discrepancy amongst those patients. Fluorescence in situ hybridization (FISH) permits the genomic identification of patients with mosaic karyotypes in interphase nuclei by utilising an X chromosome-specific DNA probe (interphase cytogenetics). We evaluated the efficiency of interphase cytogenetics in the detection of the genomic constitution of the ovary from a patient with Turner's syndrome having mosaicism (46,XX/45,X0) previously established by blood lymphocyte karyotyping. We used a biotin-labelled alphoid repetitive sequence, pBAMX5, specific for the centromeric region of the human X chromosome. Although examination of ovarian sections and blood lymphocytes by FISH showed the presence of both 46,XX and 45,X0 cell lines, the genomic constitution of the germ cells/oocytes in ovarian primordial follicles was shown to be normal (46,XX). Our results (1) show the high applicability of interphase cytogenetics on paraffin sections, (2) indicate the possibility of genomic screening of different tissues that are otherwise not amenable to routine cytogenetic investigation and (3) offer a reliable methodological approach to defining accurate by the percentage of abnormal karyotypes in mosaicism of different organs and non-dividing tissues. PMID- 7868122 TI - Analysis of a whole arm translocation between chromosomes 18 and 20 using fluorescence in situ hybridization: detection of a break in the centromeric alpha satellite sequences. AB - Using classical cytogenetic techniques, we detected a male patient with monosomy 18p/trisomy 20p, originating from a paternal reciprocal translocation of the short arms of chromosomes 18 and 20. To characterize the breakpoints further and to determine the centromeric origin of the chromosomes involved, we analyzed the metaphase chromosomes by fluorescence in situ hybridization using alpha-satellite DNA probes specific to chromosomes 18 and 20. With this approach, we showed that alpha-satellite centromeric fragments were involved in the translocation event and that the chromosome-18-specific centromeric sequences were split into two. Analysis of 14 family members from four generations revealed nine phenotypically normal individuals carrying this reciprocal translocation. These results suggest that breaks in alpha-satellite DNA fragments neither impair the centromeric function nor have clinical effects. PMID- 7868123 TI - The breakpoint on 7p in a patient with t(6;7) and craniosynostosis is spanned by a YAC clone containing the D7S503 locus. AB - We previously reported a patient with an apparently balanced t(6;7) translocation and craniosynostosis. We now demonstrate, by fluorescence in situ hybridization, that the yeast artificial chromosome clone 933-e-1 from the Centre d'Etude du Polymorphisme Humain library harbouring the D7S503 locus spans the breakpoint on distal 7p. Recent reports have defined a candidate region for a Saethre-Chotzen craniosynostosis locus between the loci D7S513 and D7S516, a region that includes the D7S503 locus. Since the translocation carrier shows only some of the symptoms characteristic for the Saethre-Chotzen syndrome, it remains unresolved whether the gene disrupted by the translocation event is the only one causing craniosynostosis in this chromosomal region. PMID- 7868124 TI - Transthyretin Ser 6 gene frequency in individuals without amyloidosis. AB - Transthyretin (TTR) Ser 6 was originally described in a Scottish kindred without amyloidosis. This variant, arising from a G-->A transition in codon 6 that destroys an MspI site and creates a BsrI site, was present in none of 50 controls, and was therefore thought to be rare. This variant has subsequently been found in a normal human cDNA liver library and in two unrelated patients with familial amyloidosis and other TTR variants, raising the question whether it is actually a common polymorphism. To address this question, we performed PCR and restriction digestion of 574 DNA samples from people without evidence of amyloidosis or a known family history of amyloidosis. The TTR Ser 6 allele frequency was 33/558 (.060) in Caucasians (including 8/192 (.04) in North American Ashkenazic Jews, 16/218 (.07) in North American non-Jews, and 9/148 (.06) in Portuguese), 3(242 (.01) in African Americans, 0/140 in Africans, and 0/208 in Asians. These data are most suggestive of a single Caucasian founder and the known 25% admixture of "Caucasian" genes in the African-American population. Alternatively, as this variant arose from a transition at a CG dinucleotide "hot spot," it may have arisen on multiple occasions. These data indicate that TTR Ser 6 is a common non-amyloidogenic population polymorphism in Caucasians. PMID- 7868125 TI - Elongated CAG repeats of the B37 gene in a Danish family with dentato-rubro pallido-luysian atrophy. AB - Dentato-rubro-pallido-luysian atrophy (DR-PLA) is considered to be rare in Europe. We describe a Danish family in which affected individuals in at least three generations have been diagnosed as suffering from Huntington's disease. Because analysis of the Huntingtin gene revealed normal alleles and various of the patients had seizures, we analysed the B37 gene and found significantly elongated CAG repeats as have been reported in DRPLA. Affected individuals with almost identical repeat lengths presented very different symptoms. Both expansion and contraction in paternal transmission was encountered. PMID- 7868126 TI - Variability of the immunoglobulin heavy chain constant region locus: a population study. AB - The Immunoglobulin Heavy chain Constant region (IGHC) locus is a multigene family composed of highly homologous segments often involved in unequal crossings over that lead to deleted and duplicated haplotypes. The frequencies of these haplotypes in 558 individuals from Lombardy, Veneto, Puglia and Sardinia were determined by Pulsed Field Gel Electrophoresis (PFGE), followed by Southern blotting with four IGHC probes, and compared with those observed in 110 subjects from Piedmont. Twenty deletions and 60 duplications were characterized, all in heterozygous individuals except for 2 homozygous deletions. The differences in frequency between the five populations were not significant. The deletions/duplications involved one or more genes: GP-A2, A1-E and G4 duplications, and A1-E and GP-A2 deletions were the most common. Four new duplications are described: three, involving the genes from GP to A2, from G2 to G4, and G4, are counterparts of known deletions. The fourth duplication spans from GP to G2. A G1 deleted heterozygous individual never previously described in Italy is reported. All the rearranged haplotypes seem to be the result of unequal crossing over. The difference between the number of duplications and deletions was significant in Sardinia, Lombardy, Puglia and in the total of 668 subjects (P < 0.001). This may be due to selection or genetic drift. PMID- 7868127 TI - Asp187Asn mutation of gelsolin in an American kindred with familial amyloidosis, Finnish type (FAP IV). AB - Familial amyloidosis, Finnish type (FAP-IV) was identified clinically in an American kindred with Scandinavian ancestry. A polymerase chain reaction (PCR) based DNA diagnostic assay was used to identify a G-to-A mutation at position 654 of the gelsolin cDNA (G654A) in this family. Molecular diagnostic testing demonstrated the mutation in individuals in three generations--the clinically affected proband, here deceased clinically affected father, and her presumably affected presymptomatic child. This report represents a rare example of FAP IV and the G654A mutation identified in a family outside Finland. The disease associated haplotype was similar to that observed in Finnish FAP IV families (suggesting common distant ancestry). PMID- 7868128 TI - Clinical characteristics of 16 cystic fibrosis patients with the missense mutation R334W, a pancreatic insufficiency mutation with variable age of onset and interfamilial clinical differences. AB - We present the genotype/phenotype correlation analysis for 16 cystic fibrosis (CF) patients who carry mutation R334W. Current age and age of diagnosis was significantly higher in the R334W/any-mutation group (P < 0.05 and P < 0.01), compared with the delta F508/delta F508 group. A slightly, but not significantly, worse lung function was found in the R334W/any-mutation group, when compared with the delta F508/delta F508 patients. The proportion of patients with lung colonization with bacterial pathogens was slightly, but not significantly, higher in the R334W/any-mutation group (71.4%), compared with the delta F508/delta F508 or R334W/delta F508 groups (55.5%). None of the R334W patients had meconium ileus but 60% were pancreatic insufficient (PI), a significantly lower proportion (P << 0.001) than delta F508/delta F508 patients. Two R334W/N1303K compound heterozygous sisters of three sibs with genotype R334W/delta F508 showed interfamilial discordant clinical data for lung and pancreatic function. The data provided here for mutation R334W demonstrate that this mutation is responsible for a less severe form of CF than delta F508. Interfamilial differences for PI and lung function suggest that other factors, viz. genetic, environmental and medical, contribute to the wide spectrum of clinical differences observed in CF patients with the same CF transmembrane conductance regulator genotypes. PMID- 7868129 TI - An inactive cytochrome P450 CYP2D6 allele containing a deletion and a base substitution. AB - The cytochrome P450 CYP2D6 is a polymorphic enzyme, for which 5%-10% of Caucasians (poor metabolizers) lack activity. The majority of mutations giving rise to the deficiency have now been identified but some individuals show anomalous phenotype-genotype relationships when screened for the common mutant alleles. We have sequenced all nine exons and intron-exon boundaries in a subject who was phenotypically a poor metabolizer but genotypically heterozygous when screened for the common alleles. A single base-pair deletion (T1795) was detected in exon 3 and a base substitution (G2064A) resulting in an amino acid substitution (G212E) in exon 4. The deletion results in premature termination of translation and a truncated protein. In a group of 50 white Americans, the allele frequency for the new mutant allele was 0.01. The new allele explains some cases of anomalous genotype/phenotype relationships for CYP2D6. PMID- 7868132 TI - Population study of a sequence polymorphism in intron 2 of the human beta-globin gene. AB - The distribution of a nucleotide polymorphism in intron 2 of the beta-globin gene (IVS-2 nt 666 C > T was examined in populations in southern Germany and Cameroon. The allelic frequencies were 0.86 for T and 0.14 for C in southern Germany and 0.87 for T and 0.13 for C in Cameroon, respectively. PMID- 7868131 TI - Somatic mutations in the neurofibromatosis type 2 gene in sporadic meningiomas. AB - Meningiomas are benign tumors of the central nervous system. Although usually sporadic, they can occur in patients affected by the autosomal dominant syndrome, neurofibromatosis type 2 (NF2). The NF2 gene has recently been isolated from chromosome 22. The presence of germline mutations in NF2 patients and the loss of heterozygosity (LOH) on 22q in NF2 tumors support the hypothesis that the NF2 gene acts as a tumor suppressor. Cytogenetic and LOH studies have suggested that the gene responsible for the development of meningiomas is located in the region of 22q in which the NF2 gene maps. The meningiomas gene could therefore be the NF2 gene itself. Recently, somatic mutations of the NF2 gene have been identified in sporadic meningiomas, thus supporting the hypothesis that the NF2 gene is also important in meningioma pathogenesis. In this study, we analyzed sixty-one sporadic meningiomas for LOH of 22q and for mutations in the NF2 gene. LOH was detected in 36 of the 60 informative tumors. Single-strand conformational polymorphism analysis was used to identify nine mutations in five of the eight exons of the NF2 gene studied. The nine tumors with an altered NF2 gene also showed LOH for 22q markers. These results further support the hypothesis that mutations in the NF2 gene are a critical pathogenetic event in at least some meningiomas. PMID- 7868130 TI - Refinement of the X-linked cleft palate and ankyloglossia (CPX) localisation by genetic mapping in an Icelandic kindred. AB - The gene responsible for X-linked cleft palate and ankyloglossia (CPX) has previously been localized to the proximal region of the q arm of the X chromosome in both Icelandic and North American Indian kindreds. In this study, further linkage analysis has been performed on the Icelandic family and has resulted in a significant reduction in the size of the interval containing the mutated gene. A new polymorphism at DXS95, together with DXS1002 and DXS349, defines the proximal boundary of the CPX interval, whereas DXYS1X defines the distal boundary. Multipoint analysis supports this localisation with a peak lod score of 12.7, more than 2 lod score units higher than the next most likely position. In order to assess the physical size of the CPX interval prior to initiating yeast artificial chromosome cloning, metaphase fluorescence in situ hybridisation analysis was performed with the closest flanking markers. The size of the interval between DXS95 and DXYS1X was estimated to be approximately 2-3 Mb. PMID- 7868133 TI - Linkage disequilibrium between a SacI restriction fragment length polymorphism and two galactosemia mutations. AB - We have identified a novel SacI restriction fragment length polymorphism (RFLP) in the human galactose-1-phosphate uridyl transferase (GALT) gene. This RFLP can be readily typed by the polymerase chain reaction (PCR). The polymorphic allele is found on about 11% of normal chromosomes and is in linkage disequilibrium with the two most common mutations identified in GALT thus far: Q188R and N314D. Q188R is found exclusively on chromosomes with the SacI restriction site, whereas N314D is found only on chromosomes lacking this site. This suggests that these two mutations arose independently in evolution on different chromosomal backgrounds. Galactosemia patients without the Q188R mutation have a frequency of the SacI polymorphism similar to normal controls suggesting that several different galactosemia mutations must be present in them. The SacI RFLP may also be useful in the prenatal diagnosis of galactosemia. PMID- 7868134 TI - Localization of the human soluble epoxide hydrolase gene (EPHX2) to chromosomal region 8p21-p12. AB - Epoxide hydrolases have an important function in organisms in that they catalyze the transformation of potentially toxic or carcinogenic epoxides into the corresponding diols. In this study, the chromosomal localization was determined for the human gene encoding soluble epoxide hydrolase. A polymerase chain reaction fragment corresponding to the C-terminal region of the mouse protein was used to isolate a cosmid clone from a human genomic library. By fluorescence in situ hybridization to metaphase chromosomes, the soluble epoxide hydrolase gene was then localized to chromosomal region 8p21-p12. PMID- 7868135 TI - SP alpha I/65 hereditary elliptocytosis in Calabria (southern Italy). AB - The alpha I/65 variant of spectrin has been described in black people, in North Africans and recently in two southern Italian families. This variant is associated in the heterozygous state with mild Hereditary Elliptocytosis (HE) and the molecular basis of the defect is invariably the duplication of TTG at codon 154 of the alpha spectrin gene. The present study reports the identification of five Calabrian families with SP alpha I/65 HE and their distribution in the population. PMID- 7868136 TI - A new restriction-site polymorphism in exon 18 of the low density lipoprotein receptor (LDLR) gene. AB - A new restriction fragment length polymorphism (RFLP) in exon 18 of the low density lipoprotein receptor (LDLR) gene is described. It should be a useful marker in linkage to familial hypercholesterolemia. PMID- 7868137 TI - A TaqI polymorphism in the human erythroid beta spectrin gene. AB - Human erythroid spectrin consists of an alpha beta heterodimer. Abnormalities of spectrin are a common cause of hereditary haemolytic anaemias such as hereditary elliptocytosis (HE) and hereditary spherocytosis (HS). To identify the spectrin gene mutation one needs initially to establish which of the spectrin subunits is defective. For this purpose, the beta spectrin restriction fragment length polymorphism (RFLP) we describe here will be useful in linkage analysis. The elucidation of an Ala-->Gly beta spectrin gene mutation in a family with HE, highlights the importance of this TaqI polymorphism in establishing linkage. PMID- 7868138 TI - Identification of two highly polymorphic CA-repeats (D21S1224 and D21S1261) on human chromosome 21q22.3. AB - Two highly polymorphic CA-repeat microsatellites (D21S1224 and D21S1261) are reported. The clones containing these CA-repeats (ABM-C60 and ABM-C29) have been isolated from a human chromosome-21-specific library (LA21NS01) and have been localised to the q22.3 band using a specific chromosome 21 somatic cell hybrid panel. Both polymorphisms showed heterozygosities of 0.83 in the unrelated reference parents from the Centre d'Etude du Polymorphisme Humain. These new markers should improve the map of the 21q22.3 region, which is believed to contain a large number of genes. PMID- 7868140 TI - A real-time electrical impedance tomography system for clinical use--design and preliminary results. AB - An instrument is described which produces images of the electrical impedance distribution within the body at a rate of 25 frames per second, allowing lung ventilation and lung perfusion to be observed in real time. The instrument makes impedance measurements using an array of 16 electrodes on the surface of the body, and reconstructs the images using a weighted backprojection technique. The design of the data acquisition electronics and the reconstruction and display processor are described. Some preliminary in vitro and in vivo results from the system are presented. PMID- 7868139 TI - Combined ultrasound and fluorescence spectroscopy for physico-chemical imaging of atherosclerosis. AB - This paper describes a combined ultrasonic and spectroscopic system for remotely obtaining physico-chemical images of normal arterial tissue and atherosclerotic plaque. Despite variations in detector-tissue separation, R, fluorescence powers corresponding to pixels in the image are converted to the same set of calibrated units using distance estimations from A-mode ultrasound reflection times. An empirical model, validated by Monte Carlo simulations of light propagation in tissue, is used to describe changes in fluorescence power as a function of R. Fluorescence spectra of normal and atherosclerotic human aorta obtained with this system are presented as a function of R. To compensate for changes in fluorescence power with R, the empirical model was used in each case to calculate the fluorescence power at a constant reference value of R(Rref = 1.67 mm). Prior to compensation, tissue fluorescence power decreased more than a factor of two as R was increased from 2.5 to 5 mm. Following compensation, the fluorescence power varied less than +/- 10% of the average compensated peak. The chemical composition of each sample was determined by fitting its fluorescence spectrum (in calibrated units) to a model of tissue fluorescence incorporating structural protein and ceroid fluorescence, as well as structural protein and hemoglobin attenuation. Parameters of the fit were used to classify tissue type. Without compensation for distance variation, classification of tissue type was frequently incorrect; however, with compensation, predictive value was high. A 1-D chemical image of a section of human aorta containing both normal and atherosclerotic regions obtained with this system is also presented. After compensation for detector-sample separation, tissue classifications along the cross-section closely resemble those obtained from histology. Regions of elevated ceroid concentration and intimal thickening are clearly observable in the resultant chemical image. The potential value of this type of system in the diagnosis and treatment of coronary artery disease is discussed. PMID- 7868141 TI - Multiple sources of the impedance cardiogram based on 3-D finite difference human thorax models. AB - Two 3-D electrical models of the human thorax, each consisting of 216,000 control volumes, were constructed based upon MR images taken at end diastole and end systole. Using the finite difference method, the contributions of various sources to the impedance cardiogram were studied for the traditional band electrode configuration. The contributions were categorized into three areas: 1) the structural changes between end diastole and end systole, 2) the flow-induced blood resistivity changes in major arteries and veins, and 3) the lung resistivity variation due to the lung blood volume change. Based on the models, Zo and delta Z between end diastole and end systole were 24.4 omega and -0.132 omega, as compared with the measurements of 21.8 omega and -0.123 omega made on the same subject from whom the images were taken. Arterial and venous blood resistivity changes caused approximately 57% of the total impedance change. The lung resistivity change and the structural changes contributed 39% and 4%, respectively. The structural changes inside the thorax included the dimensional changes of blood vessels, the blood volume changes of the heart chambers, and heart movement. Although the net impedance change due to the structural changes was relatively small, the individual variation of various factors was large, with significant cancellation occurring. The results suggest that the thoracic impedance cardiographic signal is a mixed representation of many inseparable factors and may not be reliable for the stroke volume calculation. Also, the O wave, which is clinically observed in various cardiac conditions, may be linked to the diastolic blood flow in the central veins. PMID- 7868142 TI - Average-intensity reconstruction and Wiener reconstruction of bioelectric current distribution based on its estimated covariance matrix. AB - This paper proposes two methods for reconstructing current distributions from biomagnetic measurements. Both of these methods are based on estimating the source-current covariance matrix from the measured-data covariance matrix. One method is the reconstruction of average current intensity distributions. This method first estimates the source-current covariance matrix and, using its diagonal terms, it reconstructs current intensity distributions averaged over a certain time. Although the method does not reconstruct the orientation of each current element at each time instant, it can retrieve information regarding the current time-averaged intensity at each voxel location using extremely low SNR data. The second method is Wiener reconstruction using the estimated source current covariance matrix. Unlike the first method, this Wiener reconstruction can provide a current distribution with its orientation at each time instant. Computer simulation shows that the Wiener method is less affected by the choice of the regularization parameter, resulting in a method that is more effective than the conventional minimum-norm method when the SNR of the measurement is low. PMID- 7868143 TI - An analytical model to predict the electric field and excitation zones due to magnetic stimulation of peripheral nerves. AB - The main unknown factor in understanding magnetic stimulation of peripheral nerves is the distribution of the induced electric field. We have applied the so called reciprocity theorem and developed an analytical model to compute the electric field and its spatial derivatives inside pseudocylindrical structures. The results can be used to predict the site of excitation in magnetic stimulation of peripheral nerves. PMID- 7868144 TI - The effect of morphological interdigitation on field coupling between smooth muscle cells. AB - The electrical control activity (ECA) in the distal stomach, small intestine, and colon has been modeled by populations of coupled nonlinear oscillators. Coupling has traditionally been explained through gap junctions, but gap junctions alone are inadequate, as they are not always present or cannot account for the observed behavior. Coupling through extracellular electric fields has been proposed as another coupling path which may work instead of, or in conjunction with, gap junctions. A morphological structure, the interdigitation, is studied for its effect on fields produced by a spherical cell. Using boundary element methods, the potential produced by a cell and the transmembrane potential induced in an adjacent cell are considered. Computer simulation results indicate that the presence of an interdigitation between two neighboring cells produces a 60% increase in extracellular potential and a 50% increase in induced transmembrane voltage. The interdigitation length is the most important factor, with radius playing a very small part in determining peak values of potential and voltage. These interdigitation fields may be of appreciable magnitude with regard to coupling. Also, the upstroke phase of the ECA can play a major role in intercellular communication. PMID- 7868145 TI - Computational studies of transthoracic and transvenous defibrillation in a detailed 3-D human thorax model. AB - A method for constructing and solving detailed patient-specific 3-D finite element models of the human thorax is presented for use in defibrillation studies. The method utilizes the patient's own X-ray CT scan and a simplified meshing scheme to quickly and efficiently generate a model typically composed of approximately 400,000 elements. A parameter sensitivity study on one human thorax model to examine the effects of variation in assigned tissue resistivity values, level of anatomical detail included in the model, and number of CT slices used to produce the model is presented. Of the seven tissue types examined, the average left ventricular (LV) myocardial voltage gradient was most sensitive to the values of myocardial and blood resistivity. Incorrectly simplifying the model, for example modeling the heart as a homogeneous structure by ignoring the blood in the chambers, caused the average LV myocardial voltage gradient to increase by 12%. The sensitivity of the model to variations in electrode size and position was also examined. Small changes (< 2.0 cm) in electrode position caused average LV myocardial voltage gradient values to increase by up to 12%. We conclude that patient-specific 3-D finite element modeling of human thoracic electric fields is feasible and may reduce the empiric approach to insertion of implantable defibrillators and improve transthoracic defibrillation techniques. PMID- 7868146 TI - Optimization of cardiac defibrillation by three-dimensional finite element modeling of the human thorax. AB - The goal of this study was to determine the optimal electrode placement and size to minimize myocardial damage during defibrillation while rendering refractory a critical mass of cardiac tissue of 100%. For this purpose, we developed a 3-D finite element model with 55,388 nodes, 50,913 hexahedral elements, and simulated 16 different organs and tissues, as well as the properties of the electrolyte. The model used a nonuniform mesh with an average spatial resolution of 0.8 cm in all three dimensions. To validate this model, we measured the voltage across 3 cm2 Ag-AgCl electrodes when currents of 5 mA at 50 kHz were injected into a human subject's thorax through the same electrodes. For the same electrode placements and sizes and the same injected current, the finite element analysis produced results in good agreement with the experimental data. For the optimization of defibrillation, we tested 12 different electrode placements and seven different electrode sizes. The finite element analyses showed that the anterior-posterior electrode placement and an electrode size of about 90 cm2 offered the least chance of potential myocardial damage and required a shock energy of less than 350 J for 5-ms defibrillation pulses to achieve 100% critical mass. For comparison, the average cross-sectional area of the heart is approximately 48 cm2, about half of the optimal area. A second best electrode placement was with the defibrillation electrodes on the midaxillary lines under the armpits. Although this placement had higher chances of producing cardiac damage, it required less shock energy to achieve 100% critical mass. PMID- 7868147 TI - Estimation of shear modulus distribution in soft tissue from strain distribution. AB - In order to obtain noninvasively quantitative static mechanical properties of living tissue, we propose a new type of inverse problem by which the spatial distribution of the relative elastic modulus of the tissue can be estimated only from the deformation or strain measurement. The living tissue is modeled as a linear isotropic incompressible elastic medium which has the spatial distribution of the shear modulus, and the deformation or strain is supposedly measured ultrasonically. Assuming that there is no mechanical source in the region of interest, we derive a set of linear equations in which unknowns are the spatial derivatives of the relative shear modulus, and the coefficients are the strain and its spatial derivatives. By solving these equations, the spatial derivatives of the relative shear modulus are determined throughout the region, from which the spatial distribution of the relative shear modulus is obtained by spatial integration. The feasibility of this method was demonstrated using the simulated deformation data of the simple inclusion problem. The proposed method seems promising for the quantitative differential diagnosis on the lesion in the tissue in vivo. PMID- 7868148 TI - Multiple site electromyograph amplitude estimation. AB - Temporal whitening of individual surface electromyograph (EMG) waveforms and spatial combination of multiple recording sites have separately been demonstrated to improve the performance of EMG amplitude estimation. This investigation combined these two techniques by first whitening, then combining the data from multiple EMG recording sites to form an EMG amplitude estimate. A phenomenological mathematical model of multiple sites of the surface EMG waveform, with analytic solution for an optimal amplitude estimate, is presented. Experimental surface EMG waveforms were then sampled from multiple sites during nonfatiguing, constant-force, isometric contractions of the biceps or triceps muscles, over the range of 10-75% maximum voluntary contraction. A signal-to noise ratio (SNR) was computed from each amplitude estimate (deviations about the mean value of the estimate were considered as noise). Results showed that SNR performance: 1) increased with the number of EMG sites, 2) was a function of the sampling frequency, 3) was predominantly invariant to various methods of determining spatial uncorrelation filters, 4) was not sensitive to the intersite correlations of the electrode configuration investigated, and 5) was best at lower levels of contraction. A moving average root mean square estimator (245-ms window) provided an average +/- standard deviation (A +/- SD) SNR of 10.7 +/- 3.3 for single site unwhitened recordings. Temporal whitening and four combined sites improved the A +/- SD SNR to 24.6 +/- 10.4. On one subject, eight whitened combined sites were achieved, providing an A +/- SD SNR or 35.0 +/- 13.4. PMID- 7868149 TI - Muscle-joint models incorporating activation dynamics, moment-angle, and moment velocity properties. AB - Muscle input/output models incorporating activation dynamics, moment-angle, and moment-velocity factors are commonly used to predict the moment produced by muscle during nonisometric contractions; the three factors are generally assumed to be independent. We examined the ability of models with independent factors, as well as models with coupled factors, to fit input/output data measured during simultaneous modulation of the fraction of muscle stimulated (recruitment) and joint angle inputs. The models were evaluated in stimulated cat soleus muscles producing ankle extension moment, with regard to their potential applications in neuroprostheses with either fixed parameters or parameter adaptation. Both uncoupled and coupled models predicted the output moment well for random angle perturbation sizes ranging from 10 degrees to 30 degrees. For the uncoupled model, the best parameter values depended on the range of perturbations and the mean angle. Introducing coupling between activation and velocity in the model reduced this parameter sensitivity; one set of model parameter values fit the data for all perturbation sizes and also fit the data under isometric or constant stimulation conditions. Thus, the coupled model would be the most appropriate for applications requiring fixed parameter values. In contrast, with continuous parameter adaptation, errors due to changing test conditions decreased more quickly for the uncoupled model, suggesting that it would perform well in adaptive control of neuroprostheses. PMID- 7868150 TI - An advanced signal processing technique for impedance cardiography. AB - A new design using the latest technique in signal processing, the time-frequency analysis method, was developed to process impedance cardiography signals. This technique, when used to determine the relevant calculation parameters, was found to be more accurate than conventional methods. It was shown to be advantageous in reducing ventilation artifacts and motion noise, resulting in greater accuracy. Its cardiac output values had a much better correlation coefficient when compared in the clinical setting to the standard thermodilution technique than did the values from conventional impedance cardiography devices. PMID- 7868151 TI - An extensive Markov system for ECG exact coding. AB - In this paper, an extensive Markov process, which considers both the coding redundancy and the intersample redundancy, is presented to measure the entropy value of an ECG signal more accurately. It utilizes the intersample correlations by predicting the incoming n samples based on the previous m samples which constitute an extensive Markov process state. Theories of the extensive Markov process and conventional n repeated applications of m-th order Markov process are studied first in this paper. After that, they are realized for ECG exact coding. Results show that a better performance can be achieved by our system. The average code length for the extensive Markov system on the second difference signals was 2.512 b/sample, while the average Huffman code length for the second difference signals was 3.326 b/sample. PMID- 7868152 TI - A perspective on xenograft rejection and accommodation. AB - There is increasing interest in the potential clinical application of xenotransplantation. This interest derives in part from the need to identify a more abundant source of organs for transplantation and in part from rapid progress in understanding the cellular and molecular events that contribute to xenograft rejection. Recent areas of progress include the characterization of xenoreactive antibodies which would initiate the rejection of porcine organs transplanted into primates. These antibodies consist predominantly of IgM and their binding is characterized by high avidity and surprising uniformity. Xenoreactive antibodies recognize porcine glycoproteins of the integrin family; the determinants residing on N-linked substitutions. The predominant substitution has a terminal alpha Gal residue. Antibody binding initiates activation of complement through the classical pathway triggering a number of effector mechanisms. These mechanisms may include loss of heparan sulfate from endothelial cells mediated by C5a and xenoreactive antibody; a change in endothelial cell shape mediated by C5b-7 or the membrane-attack complex; procoagulant changes mediated by the membrane-attack complex; and neutrophil adhesion mediated by iC3b. If hyperacute rejection is prevented by the depletion of xenoreactive antibody and/or the inhibition of complement, acute vascular rejection may be seen some days later. Acute vascular rejection is characterized by prominent evidence of thrombosis and neutrophil infiltration. The cause of acute vascular rejection is unknown, but may reflect profound alterations in the function of endothelial cells lining blood vessels in the graft. In some cases, when recipients of xenografts are modified by depletion of xenoreactive antibodies, acute vascular rejection does not occur; rather, a process called accommodation allows the xenograft to survive despite the return to the circulation of xenoreactive antibodies and complement. The mechanism for accommodation is not known. New therapeutic strategies including the development of specific immunoabsorbants, identification of preferred donor animals expressing low levels of antigen and the development of transgenic donor animals expressing human complement regulatory proteins are among the strategies which may bring xenotransplantation closer to the clinical arena. PMID- 7868153 TI - Immunological characteristics of islet cell xenotransplantation in humans and rodents. PMID- 7868155 TI - Xenograft tolerance. PMID- 7868156 TI - Oligosaccharides and discordant xenotransplantation. AB - The initiating factor in the hyperacute rejection of pig organs by human or non human primates is believed to be related to the presence of preformed "natural" antibodies in the host. In 1991, we demonstrated that human anti-pig antibodies were IgG, IgM and IgA and bound most strongly to oligosaccharides with an alpha galactose (alpha Gal) terminal residue. These included (i) alpha Gal-R (alpha galactose), (ii) alpha Gall-3 beta Gal-R (B disaccharide), (iii) alpha Gall-3 beta Gall-4 beta GlcNAc-R (linear B type 2 trisaccharide) and (iv) alpha Gall-3 beta Gall-4 beta Glc-R (linear B type 6 trisaccharide) where R is (CH2) 8COOCH3. In vitro studies using both the chromium release assay and a live/dead staining technique demonstrated that the cytotoxicity of human sera towards pig cells can be significantly reduced or abolished by immunoadsorption of the serum with immunoaffinity columns of an alpha Gal structure, particularly those with an alpha 1-3 linkage, and not by a large selection of other carbohydrates. Similarly, human anti-pig antibodies can be largely inhibited or "neutralized" by the addition of an alpha 1-3Gal di- or trisaccharide to the serum. Staining of pig vascular endothelium utilizing a panel of carbohydrate-specific lectins and immunoaffinity antibodies demonstrated the presence of three different carbohydrate epitopes, namely (i) alpha Gall-3 beta Gall-4 beta GlcNAc-R (linear B type 2 trisaccharide (ii) alpha NeuAc2-3 beta Gall-4 beta GlcNAc-R (sialyl-N acetyllactosamine), and (iii) beta Gall-4 beta GlcNAc-R (N-acetyllactosamine). We have investigated organs from several breeds of pig and have concluded that the alpha Gal epitope is either monomorphic or at least has a high incidence in porcine species, since we have not found any pig negative for this antigen. Human vascular endothelial cells have at their surface the same lactosamine-ended precursor and sialylated chains as pigs, but instead of terminal alpha Gal they express the fucosylated polymorphic ABH histo-blood group epitopes. As we have found no evidence that human or baboon plasma contain antibodies directed against sialic acid or lactosamine, and as human tissues contain both of these carbohydrates, it seems unlikely that either of these epitopes plays a role in the vascular rejection that takes place when pig organs are transplanted into primates. Unfortunately, the alpha Gal disaccharide and trisaccharides were not available to us in the large quantities required for extracorporeal immunoadsorption or continuous intravenous infusion in adult baboons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7868157 TI - Endothelial cell activation and thromboregulation during xenograft rejection. PMID- 7868154 TI - The biological basis of and strategies for clinical xenotransplantation. AB - Recent discoveries have suggested that the exchange of multiple leukocyte lineages between grafts and host and subsequent long-term chimerism in both is the seminal mechanism of the acceptance of organs transplanted from the same (allografts) or different species (xenografts). This insight suggests new strategies which may allow xenotransplantation, the principal obstacle to which has been humoral rejection. We have defined humoral rejection as a family of complement activation syndromes afflicting allografts and xenografts in which there is a strong (but not invariable) association with performed antigraft antibodies, invariable evidence of complement activation, histopathologic stigmas of vascular endothelial damage, and a concomitant local or systemic coagulopathy. The generic descriptive term hyperacute rejection is a misnomer because a slow motion version of the same "humoral" process can occur with some allografts and is the rule with the so-called concordant species xenotransplantations. The pathway of experience and discovery leading to this conclusion shows clearly that the distinction frequently made between allograft versus xenograft humoral rejection does not actually exist in principle, but only in details and intensity. Breaking down this barrier to xenotransplantation, whether or not it is associated with antibodies, is unrealistic. However, the possibility of avoiding the barrier has been exposed by showing that animal organs can be humanized, with a mixed donor and recipient cell population similar to the chimerism seen in long surviving allografts or even with complete leukocyte replacement. Pilot experiments in rodents suggest that organs from fully xenogeneic chimeras can be made into xenogeneic targets that are no more provocative of complement activation than allografts when they are transplanted into the donor bone marrow species. Although the validity of this concept of organ xenograft preparation is only at the pilot stage of verification, there is reason to suspect that the complement trigger of humoral rejection can be thereby disarmed. If this can be accomplished, independent evidence suggests that cellular rejection can be controlled with conventional T-cell directed immunosuppression, perhaps even with surprising ease. The potential subtle liability of synthetic products of xenogeneic parenchymal cells is not yet known. PMID- 7868158 TI - Early events in cell-mediated recognition of vascularized xenografts: cooperative interactions between selected lymphocyte subsets and natural antibodies. AB - Cell-mediated early immune recognition of xenogeneic vascularized discordant grafts is poorly characterized. It has been the purpose of our studies to elucidate the role of lymphocytes in the recognition and rejection phenomena. To this end, we have utilized both ex vivo and in vitro model systems. We demonstrate that selected human lymphocyte subpopulations (mainly NK cells) rapidly and specifically adhere to xenogeneic endothelia. Efficient lysis of endothelial cells is subsequently mediated by such a population. Adhesion and cytotoxicity occur via at least two pathways, one dependent on and the other independent of the presence of human natural antibodies of the G class. Both IgG dependent and IgG-independent adhesion and cytotoxicity can be partly inhibited by the use of anti-leukocyte integrin monoclonal antibodies. IgG-dependent adhesion and cytotoxicity can be also partly inhibited by carbohydrate structures that contain the alpha-galactosyl epitope. A possible role of these events in the eventual outcome of discordant vascularized xenogeneic transplants can be postulated. PMID- 7868159 TI - Depletion of IgM xenoreactive natural antibodies by injection of anti-mu monoclonal antibodies. AB - It is believed that IgM xenoreactive natural antibodies (XNA) and activation of complement are the two main effectors involved in the hyperacute rejection (HAR) of discordant xenografts, such as pig-to-primate kidney, liver or heart transplants. We have hypothesized that long-term depletion of circulating IgM XNA might be able to overcome HAR and induce the "accommodation" of pig-to-primate vascular discordant xenografts. Several techniques have been described to eliminate circulating XNA in primates but, up to now, none has been able to totally deplete these antibodies for a sufficiently long period of time in order to test the hypothesis of discordant xenograft "accommodation". Previous reports from our laboratory have shown that, in rodents, B-cell immunosuppression could be achieved by neonatal administration of anti-mu antibodies. Recently we have shown that administration of an anti-mu mAb, in adult rats, was able to totally deplete circulating IgM and IgM XNA, without immune complex disease. Furthermore, we have used different methods such as splenectomy, plasma exchange and an anti-B cell immunosuppressive agent mycophenylate mophetil (RS61443, Syntex, Palo Alto, USA) to pre-deplete circulating IgM before administration of anti-mu mAb (MARM-7) and showed that the effectiveness of anti-mu mAb to deplete circulating IgM was increased by 100-fold. Depletion of circulating IgM in adult rats by anti-mu mAb (MARM-7) was used as an experimental model to study the role of IgM XNA in the pathogenesis of HAR in guinea pig-to-rat cardiac xenografts. Our data show that IgM XNA play a major role in HAR, even if in this discordant combination direct activation of complement, probably through the alternative pathway, seems to be the main effector involved in HAR. We have analyzed the mechanisms of anti-mu depletion of circulating IgM in adult animals and shown that, besides anti-mu/IgM immune complex formation, depletion of circulating IgM results from the very significant inhibition of B-cell differentiation and secretion of IgM following in vivo crosslinking and internalization of surface IgM on B cells. As well, we provide evidence demonstrating that anti-mu mAb blocks B cells at an early stage of maturation, probably in the bone marrow. Furthermore, we have developed several rat anti-human and anti-baboon IgM mAb and tested their ability to deplete circulating IgM and IgM XNA in baboons, after splenectomy or splenectomy and plasma exchange.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7868160 TI - 25th Meeting of the Society of Immunology. Konstanz, Germany, September 21-24, 1994. Abstracts. PMID- 7868161 TI - Prevention of mercuric chloride induced histopathological changes in the small intestine of mice with LIV-52. AB - Mercuric chloride was administered in drinking water to mice at 1 mM and 5 mM for 100 and 30 days respectively. Lower concentration caused mild pathological changes in the small intestine while higher concentration caused severe pathological changes. Pathological symptoms were less pronounced when Liv52 was administered along with 5 mM mercuric chloric and Hg-induced changes were totally absent when drug was used along with 1 mM HgCl2 solution. After Hg-exposure at both concentrations mice were allowed to recover naturally or with drug (Post therapy). Again, use of drug appeared useful. At least under laboratory conditions this herbal drug seems to reduce Hg-induced pathological changes in small intestine of mice. PMID- 7868163 TI - Swallowed sharp foreign bodies (sewing needles): a conservative approach. AB - A swallowed foreign body, large or small, sharp or pointed should be treated with respect. Its passage in the gastrointestinal tract should be carefully watched and monitored. The patient should be kept under regular and constant observation until such time as the foreign body has either expelled itself or is removed. We report here two cases of sharp foreign bodies ingested by children and successfully managed on conservative lines. PMID- 7868162 TI - Fatty acid profile and the atherogenic risk in fish consuming and non fish consuming people. AB - Epidemiological studies have indicated a lower incidence of cardiovascular disease in populations with a high habitual intake of marine fish and fish oils, and this apparent protection may be due to the presence of n-3 fatty acids in the dietary fish. Two populations, a rish consuming one from coastal area and an inland one with non fish consuming from Nellore district or South India were selected for the present study. A total of one thousand healthy subjects were randomly chosen (500 in each population) from both sexes, aged from 20 to 70 years. The concentration of serum cholesterol, triacylglycerol and LDL cholesterol were significantly lower in fish consumers, whereas HDL-cholesterol was higher in fish consumers than in non fish consumers. The difference between the percent quantities of the three n-3 fatty acids (eicosapentaenoic, docosapentaenoic and docosahexaenoic acids) was highly significant (p < 0.001) with a greater value in fish consumers. PMID- 7868165 TI - New research on killing cancer cells. PMID- 7868164 TI - India most afflicted by oral cancer. PMID- 7868166 TI - A new diagnostic alternative to vasography and testicular biopsy. PMID- 7868167 TI - Integrity, coordination and inter-relationship of laboratories in patient care services. PMID- 7868168 TI - Mast cells and macrophages in endometrial lesions. AB - One hundred and forty cases of endometrial lesions including 128 endometrial polyps, 7 cases of atypical hyperplasia and 5 cases of endometrial carcinoma were studied for mast cells and macrophages. Thirty six uteri with normal cyclic variations served as a control group. A cyclical variation in the mean mast cell value was observed in the control group with an increase in the secretory phase. Endometrial polyps showed a decrease in average mast cell count compared to the proliferative phase controls. Mast cells were significantly decreased in atypical hyperplasia and were absent in endometrial carcinoma. The observations indicate a hormonal basis for the significant variation in mast cell. Their presence probably suggests benign nature of the lesion. PAS positive macrophages were seen only in 4 endometrial polyps, too small for assessment of their significance. PMID- 7868169 TI - Evaluation of two techniques (RPHA and latex agglutination) for use as a screening tool for HBsAg. AB - RPHA and latex agglutination are two cost effective techniques available for HBsAg screening in our country. Most of the blood banks and other clinical laboratories use RPHA technique or latex agglutination test for screening of donors or patients positive for Hepatitis B surface Ag (HBsAg). All the reagent kits available in the Indian market do not give the ranges of specificity, sensitivity and predictive values for the particular test. Also no data is available if they were tested on Asian sera. Therefore it was decided to evaluated the two most often used techniques RPHA and latex agglutination for their sensitivities and efficacy as a screening test. Our results indicate that though RPHA may be used in a diagnostic set up, it is a poor screening tool as it gives a fairly large number of false negatives and has a low sensitivity. Latex agglutination on the other hand, does not give any false negative results and is recommended for preliminary screening, wherever cost is a constraint. The sera with positive results should be subsequently tested by EIA to rule out the false positive results. PMID- 7868170 TI - Antidermatophytic activity of allylamine derivatives. AB - The allylamine derivatives are a new class of synthetic antifungal agents. The antidermatophytic activity of the two main compounds, naftifine and terbinafine were compared in vitro with those of ketoconazole and itraconazole by agar dilution. Eighty eight clinical isolates of dematophytes comprising of Microsporum canis (50), M. audouinii (5), Trichophyton rubrum (6) T. mentagrophytes (5), T. violaceum (12), T. simii (5), T. verrucosum (1), T. soudanense (1), T. erinacie (1) and Epidermophyton floccosum (2) were tested. Terbinafine was found to be most active, inhibiting 68 of the 88 isolates at a concentration of 0.01 ug ml-1 and all at 0.1 ug ml. (Minimum inhibitory concentration - MIC range < or = 0.0001-0.1 ug ml-1). Naftifine inhibited 84 isolates at a concentration of 0.1 ug ml-1 and all at 0.5 ug ml-1 (MIC range 0.001-0.5 ug ml-1). Itraconazole required 0.1 ug ml-1 for inhibiting 50 isolates and 0.5 ug ml-1 for 85 isolates (MIC range 0.01-1 ug ml-1) whereas ketoconazole inhibited 71 isolates at 1 ug ml-1 and 87 at 2.5 ug ml-1 (MIC range 0.01-5 ug ml 1). PMID- 7868171 TI - Fungal colonization in gastric ulcers. AB - Until now studies on fungal colonization of gastric ulcers were retrospective involving small series of patients. This prospective study of 50 patients with gastric ulcers (25 benign and 25 malignant) revealed colonization by Candida in 17 (34%) cases. There was no significant difference in colonization between benign and malignant ulcers. Follow up revealed no difference in healing of ulcers with or without fungal colonization. PMID- 7868172 TI - Prevalence of nocardiosis and use of Modified Thayer Martin medium. AB - 5 cases of pulmonary and 1 case of cerebral nocardiosis in the form of abscess caused by Nocardia asteroides were detected in a study of 498 clinical specimens from 428 patients of suspected tuberculosis and mycoses, giving an overall prevalence of 1.4 percent. Modified Thayer Martin Medium was useful for recovery of two isolates of N. asteroides from 100 patients. These isolates also grew on other media but on MTM, no hampering admixture of commensals occurred. PMID- 7868173 TI - Serotyping of pulmonary isolates of Candida albicans. A preliminary study. AB - A total of twenty strains of Candida albicans isolated from chronic pulmonary lesions were subjected to serotyping procedure adopting the conventional agglutination reactions. Prior to serotyping all the twenty strains were isolated on at least three different occasions and were identified by the standard accepted criteria (germ tube production, colony morphology on cornmeal Tween 80 agar and sugar fermentation reactions). Of the twenty strains, four strains belonged to serotype B and the remaining sixteen had the agglutination profile consistent with serotype A. The serotyping was undertaken with locally raised antisera against serotype A and serotype B. The proposed serotyping procedure has a definite potential in the epidemiological investigations of Candida albincans. PMID- 7868174 TI - Bacteriological study of bronchoalveolar lavage in immunocompromised hosts. AB - Sixty bronchoalveolar lavage samples collected from lung cancer patients attending the Pulmonary Tuberculosis and Chest Diseases Unit of the Kasturba Medical College Hospital, Manipal; were cultured for both the aerobic and anaerobic organisms. Fifty nine samples yielded bacteria in pure culture. Pseudomonas aeruginosa (34.8%) was the commonest aerobe, Peptostreptococcus was the commonest anaerobe (45.2%) isolated. Bacteroides fragilis was isolated in (23.8%) of cases. Gentamycin was found to be effective against aerobes, Metronidazole and Rifampicin against anaerobes. PMID- 7868175 TI - Bacteraemia in urological surgical procedures. PMID- 7868176 TI - Study of diphtheria antibody levels in healthy population. AB - Diphtheria antibody levels were analysed in 200 healthy individuals by Indirect Haemagglutination test. The antibody titres in the age groups 1-5 and 6-10 years were well above the protective level. The titre declined with increase in age. In 11-20 years of age about 17.5 per cent, in 21-30 years of age 52.5 per cent and in persons above 30 years of age 82.5 per cent people had antibodies below protective level. Our results are comparable to studies from India and abroad. Emphasis is given for reconsideration of immunisation programme in higher age group. PMID- 7868177 TI - Propagation of Salmonella 3, 10: r in ileum: a transmission electron microscope study. AB - Salmonella 3, 10: r organisms were examined ultrastructurally for their role in the initiation of infection in chicken ileum and studied 18 hr after, the organisms were seen located free as well as in contact with food particles. The surface features of the organisms revealed marked changes when they were located close to the ileal epithelial cell microvilli. The organisms were also seen having penetrated into intercellular spaces located in the interior of ileum. Many of them were seen phagocytosed by phagocytic cells. PMID- 7868178 TI - Problems in laboratory investigations and management of transfusion in patients with antibodies to high frequency antigens (a report on two cases with anti-Kpb). PMID- 7868179 TI - Neonatal Salmonella havana meningitis. AB - The clinical features, microbial characterisation and autopsy findings in a premature neonate with Salmonellas havana meningitis is presented. S. havana is a very rare pathogen in India. PMID- 7868180 TI - Necrotizing myelopathy--a report of two cases with review of literature. AB - Necrotizing myelopathy is an uncommon neurological disorder. Till 1991, only 31 cases have been described in the literature. In this report, clinical and neuropathological features in two patients with necrotizing myelopathy are described. The precise aetiological agent in first patient was undetermined, However in the second patient there was serological evidence, suggestive of Herpes simplex virus infection. PMID- 7868181 TI - Necrotising fascitis. PMID- 7868182 TI - Primary adenocarcinoma of the urinary bladder--a case report with review of literature. AB - Primary adenocarcinoma of the urinary bladder is a rare neoplasm. We present the clinicopathological and immunohistochemical analysis of a case in a 50 year old male. The histogenesis of the tumour and a review of literature is also discussed. PMID- 7868183 TI - Paraganglioma of the cauda equina region--a report of two cases with review of literature. AB - Among all extra-adrenal locations, paragangliomas are least commonly found within the spinal canal. so far over 60 cases of paragrangliomas in the Cauda equinal region have been reported. In this report we describe the salient clinical and histopathological features of paraganglioma of the cauda equinal region in two patients. PMID- 7868184 TI - Stromal sarcoma of uterus; report of two cases. PMID- 7868185 TI - Induction of nerve growth factor responsiveness in C6-2B glioma cells by expression of trkA proto-oncogene. AB - Cells that lack the high affinity receptor component (trkA) for nerve growth factor (NGF) are unresponsive to NGF. We investigated whether C6-2B cells, a rat glioma derived cell line, express trkA and, as a consequence, are responsive to NGF. In these cells, NGF (100 ng/ml) failed to induce the mRNA encoding for c-fos protooncogene and the low affinity NGF receptor p75NGFR, two NGF-responsive genes. In contrast, both mRNAs were induced in PC12 cells by NGF. Using a RNase protection assay with a cRNA probe for rat trkA, the expected trkA RNA protected fragment was detected in PC12 but not in C6-2B glioma cells, indicating that C6 2B cells either do not express the gene or express it only in low amounts. Cross linking of 125I-labeled NGF to PC12 cells identified two major bands with an apparent molecular weight of 158 kDa and 100 kDa corresponding to trkA and p75NGFR, respectively. In contrast, only the 100 kDa band could be detected in C6 2B cells by cross-linking analysis. In C6-2B cells stably transfected with the rat trkA cDNA, NGF increased c-fos mRNA, induced tyrosine phosphorylation of gp140trk, and SNT (suc-associated neurotrophic factor-induced tyrosine phosphorylated target), and caused morphological changes within 72 h. All of these effects of NGF were blocked by the protein kinase inhibitor K-252a suggesting that NGF signal transduction was restored by trkA expression. Most important, in C6trk+ cells, NGF was a weaker (2-fold) inducer of [3H]thymidine incorporation when compared to bFGF (5-fold), suggesting that expression of trkA fails to confer to NGF a strong mitogenic effect. Our findings indicate that C6 2B glioma cells do not possess high affinity NGF receptor and thus are unresponsive to NGF and that expression of trkA in neuroectoderm derived cells elicits some of the NGF responses characteristic of neuronal cells. PMID- 7868186 TI - Ryanodine-induced intracellular calcium mobilisation in cultured astrocytes. AB - Changes in intracellular Ca2+ concentration were monitored in cultured cortical astrocytes challenged with ryanodine and ATP. Ryanodine elicited a modest, in comparison to ATP, increase in cytosolic Ca2+ concentration in approximately 60% of the cell fields examined. This effect was evident and, in fact, was augmented when incubations were performed in Ca(2+)-free bathing medium. In addition, ryanodine-evoked changes in intracellular Ca2+ concentration were dose dependent, desensitised rapidly, and could not be mimicked by caffeine. Exposure to ryanodine was without effect on eicosanoid release from these cells nor did it influence Ca2+ mobilisation and eicosanoid release in response to ATP. In contrast, caffeine attenuated part of the ATP-evoked increase in intracellular Ca2+ concentration in the majority of cells tested and abolished its effect on eicosanoid release. PMID- 7868188 TI - Maturation of the GFAP-immunopositive glial network is delayed in the olfactory bulbs of rats subjected to early, low-dose X-irradiation. AB - Young rats were subjected to low-level, repeated doses of x-irradiation from a Co60 source and examined for the presence and arrangement of their GFAP immunopositive system at the light and electron microscopic levels. In 2-week-old control rats, labelled cells were already distributed homogeneously throughout the bulb, while in the experimental animals, a (newborn- and early postnatal type) radial arrangement of immunoreactive fibres continued to persist even until the end of the fourth postnatal week. This delay in the maturation of the GFAP immunopositive glial system may contribute to the hindered development of the bulbar neurones, neuronal connections, and field potentials, as found in earlier studies. PMID- 7868187 TI - Regulation of metallothionein-I+II levels in specific brain areas and liver in the rat: role of catecholamines. AB - The role of the catecholamines noradrenaline, adrenaline and dopamine on metallothionein (MT) levels of specific areas of the rat brain has been studied. MT-I or MT-I + II levels were measured by radioimmunoassay using specific antibodies that cross-react only slightly with human MT-III (growth inhibitory factor, GIF). The inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine (MPT), which depletes brain dopamine, noradrenaline, and adrenaline, increased MT levels in all brain areas studied (frontal cortex, cortex, medulla oblongata plus pons, midbrain, striatum, hippocampus, hypothalamus, and cerebellum) when considering the results of two separate experiments. The alpha- and beta-receptor blockers, phentolamine, and propranolol, alone or together, did not increase brain MT levels in any area of the brain, suggesting that the effect of MPT in vivo is related to inhibition of the synthesis of dopamine rather than of noradrenaline and adrenaline. Dopamine, noradrenaline, and serotonin increased MT I levels in primary cultures of neurons, whereas decreased them in astrocyte enriched primary cultures. Since MT-I levels are about ten times higher in astrocytes than in neurons, the increased brain MT levels induced by MPT may reflect the suppression of the normal inhibitory effect of dopamine on astrocyte MT levels. The increase in MT concentrations induced in most parts of the brain by immobilization stress was not prevented by MPT, phentolamine, or propranolol, suggesting that it was not mediated by the central monoamines. PMID- 7868189 TI - Expression of BMP-6, a TGF-beta related morphogenetic cytokine, in rat radial glial cells. AB - Bone morphogenetic protein-6 (BMP-6) is a member of the TGF-beta superfamily of cytokines. The bone morphogenetic proteins and homologous cytokines participate in realization of the genetic body plan by regulating homeotic gene expression, embryonic development, and neurogenesis. Here we demonstrate expression of BMP-6 in rat radial glial cells which are involved in embryonic organisation of the central nervous system. Thus, morphogenetic cytokines like BMP-6 might contribute to radial glial cell function in organizing the migration of immature neurons during the development of the CNS cortex. PMID- 7868190 TI - Denervated skeletal muscle stimulates migration of Schwann cells from the distal stump of transected peripheral nerve: an in vivo study. AB - We have tested the stimulation of Schwann cell migration from the distal stump of a 1 week transected sciatic nerve of adult rats by denervated skeletal muscle. Migrating Schwann cells were distinguished by the presence of non-specific cholinesterase (nChE) activity and glial fibrillary acidic protein (GFAP) at a distance of about 6 mm among denervated muscle fibres 4 weeks after insertion of the distal stump. In addition, the distal stump was introduced into the open end of a silicone chamber packed with artificial fibrin sponge (Gelaspon) soaked in homogenate from intact or denervated muscles. A larger amount of migrated Schwann cells was observed in the chambers filled with homogenate from denervated muscles. An alteration in the amounts of Schwann cells migrating into the silicone chambers observed after histochemical staining (nChE or GFAP) was supported by biochemical measurements of the nChE activity. The biochemical assessment of the nChE activity revealed the increased amounts of migrated Schwann cells in proportion to the protein contents of homogenates from the denervated muscles. In addition, heating of homogenate from the denervated muscles resulted in a diminution of Schwann cell migration. Bromodeoxyuridine incorporation did not show an increased proliferation of Schwann cells inside the chambers following application of homogenate from the denervated muscles in comparison with the homogenate from the innervated muscles. Our results suggest a stimulation of Schwann cell migration from the distal stump of the transected sciatic nerve by soluble factor(s) produced by denervated skeletal muscles. PMID- 7868191 TI - Fracture of the distal radius: classification of treatment and indications for external fixation. AB - A number of classifications have been created for fractures of the distal radius. We describe those of Older et al., Frykman, Thomas, Melone, McMurtry, Fernandez, the Mayo and the AO/ASIF. These classifications help to identify unstable fractures and offer insight into the indications for external skeletal fixation. PMID- 7868192 TI - History, evolution and biomechanics of external fixation of the wrist joint. PMID- 7868193 TI - Development of the small AO fixator to the current set. AB - An indirect system to reduce and hold comminuted fractures of the distal radius was developed in the mid 1970's starting with a simple threaded distraction rod and advancing to a versatile system of rods and universal clamps. This system has gained wide acceptance since then and is used for the wrist joint and for other indications in surgery of the hand, the upper limb, the foot and in paediatric orthopaedics. PMID- 7868194 TI - The small AO external fixator--a versatile device. PMID- 7868195 TI - Combination of the small external fixator and standard tubular system. AB - A modification of the standard setup of the small external fixator is presented for use mainly on the wrist. The setup used since 1988 offers further possibilities as compared with conventional application: Completely free positioning of the wrist joint for all possible six degrees of freedom, therefore: Better possibility to postpone manual reduction until the frame is applied ("modular" fixator frame, comparable to the tube-to-tube configuration of the standard external fixator), Easy correction of axial, flexural and rotational malalignment during surgery with the external fixator in situ and without changing the pin position, Easy relaxation of overdistraction postoperatively, Temporary postoperative mobilization of the wrist joint possible. Better preoperative distraction due to higher force and longer distance of the compression/distraction device. Rigid construction by using comparably short threaded K-wires and large diameter connecting bar. Less interference with peri- and postoperative imaging techniques. PMID- 7868196 TI - Complications of external fixation of the wrist. PMID- 7868197 TI - Twelve years follow-up of fractures of the distal radius treated with the AO external fixator. AB - From 1977 to 1982 a total of 55 patients suffering comminuted fracture of the distal radius were treated with the external fixator. Fifty of these were followed up in 1983/85 and 32 of them were available for assessment in this study (1992). The follow-up period was 11.6 years on average. All patients had suffered an intra-articular fracture (91% a C-fracture, 9% a B-fracture according to the AO classification), 27 patients had also fractured the ulnar styloid process and in 11 a dye-punch fragment was present. Both wrists were assessed on the basis of case history, clinical examination, radiographs in two planes and visual analogue scales (VAS). The results were evaluated using established scoring systems. On the Gartland and Werley scale 75% of the results were good or very good, 63% according to Castaing. In general, there was no statistically significant difference between the results of this study and those of 1983/85. It could be demonstrated that there was a relationship between arthritis as a late complication and the existence of an intra-articular step-off of at least 2 mm at implant removal. This also has a negative influence on the range of motion and strength. Radial shortening affects the functional result whereas a die-punch fragment does not. On VAS patients identified performance restriction and disability as the worst consequences of the accident; these criteria correlated best with the results of objective evaluations. In contrast, patients were more satisfied with the result of treatment than would be expected from the objective analyses. The overall results indicate that exact reduction was extremely important. Long-term follow-up showed that the use of the external fixator in the treatment of comminuted intra-articular fractures of the distal radius was an adequate method. Prospective and possibly multicentric studies would be required to investigate more detailed relationships between treatment and long-term results. PMID- 7868198 TI - The small AO external fixator in hand surgery. AB - At our institution, the small AO external fixator has been utilized on the wrist and hand on over 200 patients since 1979. Disregarding fractures of the distal radius, the main indications were fracture dislocations of the wrist, Kienbock's disease, combined injuries with bone defects of the wrist and metacarpals, and basilar fractures of the thumb metacarpal. In this paper, five well-established applications will be described with respect to treatment concept, indication, technique, and personal results. Furthermore, recommendations and reservations are listed to help in the prevention of the most frequent complications. PMID- 7868199 TI - Other applications of the small AO external fixator to the upper limb. PMID- 7868200 TI - Other applications of the small AO external fixator to the lower limb. PMID- 7868201 TI - The small AO external fixator in paediatric orthopaedics and trauma. PMID- 7868202 TI - Three-dimensional dynamic AO external fixation of distal radial fractures--a preliminary report. AB - External fixation of unstable and intra-articular distal radial fractures has become increasingly popular. Dynamic external fixation, allowing movement of the wrist during the fixation period, is a relatively new approach which may further improve functional end results. To permit early functional treatment, the small AO external fixator was supplemented by a joint allowing all three degrees of rotational freedom. The centre of rotation is located at a point outside the device and lies approximately in the head of the capitate. With the natural centre of wrist rotation coincident with that of the fixator, admissable movements of the wrist include both flexion-extension and radio-ulnar deviation, without threatening fracture reduction. In vitro testing and initial clinical experience with a prototype are encouraging. Several improvements of the original design have been made and a multicentric clinical study is scheduled for further evaluation of the new dynamic external fixator. PMID- 7868203 TI - Seidel interlocking nailing for healing problems in humeral shaft fractures. AB - In 14 patients aged 38 to 87 years humeral shaft fractures were operated on for failure of reduction, for delayed healing or for established non-union with the Seidel interlocking nail system. In five patients intraoperative technical problems were encountered. The healing rate was eight out of 12 patients. In cases of pseudarthrosis of the humeral shaft, bone grafting or local osteosynthesis in addition to medullary nailing seem advisable. The distal interlocking mechanism of the Seidel nail should be improved. PMID- 7868204 TI - The perceived relationship between neck symptoms and precedent injury. AB - A questionnaire survey of 328 hospital employees was used to establish the general prevalence of neck symptoms related to everyday activities in a representative population of working society. The response rate was 92 per cent. Of the study population of 302, 54 had suffered neck injury, and of this group, 43 (80 per cent) had some neck discomfort during or after performing normal everyday tasks. Of the symptomatic cases, only seven (16 per cent) admitted that they had suffered from some neck symptoms before the injury, whilst 36 (84 per cent) attributed all of their neck symptoms to the injury sustained. Of the total population, 248 had not suffered a neck injury and of this group 84 (34 per cent) suffered some neck discomfort during or after performing normal everyday tasks. The chi 2 test was used to test the null hypothesis that the sub-group attributing their symptoms to injury, in whom only 16 per cent acknowledged pre existent neck symptoms, was derived from the same population as the group who had not suffered any definite neck injury, and yet were still troubled with some neck symptoms in 34 per cent of cases. This hypothesis was rejected (P < 0.01), indicating that there was a significant difference between these two groups. We conclude that some individuals who suffer a neck injury do not recall that they suffered some minor neck symptoms before injury. The statistical analysis and alternative possible explanations are discussed. Our conclusions may be of medico legal importance in cases where compensation is being sought. PMID- 7868205 TI - Open fractures of the tibia in children. AB - The results of the treatment of open tibial fractures in 58 children aged between 3 and 15 years are reviewed. There were 25 Gustilo Type I, 22 Type II and 10 Type III fractures. At operation 37 wounds were closed primarily and 21 wounds were left open. Of these 21, 13 healed by secondary intention and eight required split skin grafting or soft tissue flap coverage. Stable fractures were immobilized in an above-knee plaster in 48 cases (83 per cent) and six fractures treated with external fixation (10 per cent). Two patients (3.5 per cent) had cast immobilization of the tibial fracture and traction for an ipsilateral femoral fracture. Two patients (3.5 per cent) with Gustilo Type IIIc injuries required an amputation, one 'de novo' as the limb was not salvageable and one 4 days after failed vascular reconstruction. All fractures healed primarily without bone grafting, although there were three cases of delayed union and seven cases of malunion. Six children had superficial wound infections but there were no cases of deep infection or osteomyelitis. There was one case of compartment syndrome. PMID- 7868206 TI - Major trauma workload within an English Health Region. AB - The incidence, distribution and clinical patterns of life-threatening and multiple injuries were evaluated within an English Regional Health Authority area. Cases of major injury were identified retrospectively for the 12 month period October 1988 to September 1989 using data from the 16 Accident and Emergency (A&E) units within the Yorkshire Health Region, and coroners' records. There were 968 cases of fatal and serious injury, meeting the criterion of an injury severity score greater than 15, 67 per cent (645) being due to road traffic incidents. Thirty-five per cent (337) died at the scene or before reaching hospital, whilst 65 per cent (631) survived to reach an A&E unit (0.082 per cent of the Region's annual A&E case load), 75 per cent arriving outside of normal office hours. Eleven per cent (72) died prior to ward admission and 34 per cent (213) were immediately transferred to a secondary medical referral centre. Three hundred and sixty-seven patients (38 per cent) survived to be discharged from acute hospital care whilst 188 (19 per cent) died as in-patients. Major injuries were found to be distributed throughout the Authority area in rough proportion to district population density with a regional incidence of 27 cases per 100,000. This study has quantified a group of patients with very specific and specialized needs, but further research and debate is required to decide how these needs are best met. PMID- 7868207 TI - Sports fractures of the distal radius--epidemiology and outcome. AB - Of 2774 consecutive, prospectively documented fractures of the distal radius, 225 (8 per cent) occurred as sports injuries, mainly in young men. Soccer produced the greatest number of wrist fractures with 112 cases (50 per cent). Skiing, dancing and rugby caused 12 per cent, 9 per cent and 7 per cent of all sporting wrist fractures respectively. Skiing, horseriding and dancing consistently resulted in more complex fractures. In soccer, synthetic pitches increased the likelihood of a fracture following a fall by a factor of five. Twelve per cent of fractures required further treatment because of instability leading to redisplacement. The complication rate was 14 per cent with the majority being cases of malunion (12 per cent). Of the 131 patients who returned a questionnaire, 72.5 per cent had returned to their original sport. This was influenced mainly by the patient's age and pre-injury standard of competition. PMID- 7868208 TI - Severe dog-bite injuries, introducing the concept of pack attack: a literature review and seven case reports. AB - Attacks on humans by dogs acting as a pack, though uncommon, result in severe, sometimes fatal, injuries. We report seven cases of attacks by packs of dogs (five on children and two on elderly women) including one fatal case. The dangers of dogs acting as a pack are highlighted, particularly when confronted with an unaccompanied child or elderly female. The pattern of injuries and principles of treatment are discussed. PMID- 7868209 TI - Patterns of splenic injuries seen in skiers. AB - Splenic rupture secondary to skiing appears to fall into two distinct epidemiological patterns: high-speed impact with stationary objects and simple falls (mogul injury). Of 18 splenic injuries seen at a referral hospital over 12 years, six were high-speed collisions with trees, lift towers or other solid objects. Twelve were low-speed falls impacting on moguls, the ski trail or low speed impact with a trailside object (stump or rock). Those who sustained low speed injuries frequently skied down the mountain afterwards without assistance (8/12), and had no other significant concomitant injuries other than minor renal contusions compared with the collision group (P < 0.005). The rate of splenic salvage was also higher in this group than in the collision group (68 per cent vs 17 per cent). The six high-speed collision splenic injury victims were all transported down the mountain by toboggan, and all had significant associated injuries. The incidence of concomitant renal injuries with splenic injuries in both groups was higher than in other reported series (10 of 18 patients). Some of those who skied down the mountain themselves sought medical attention only when they experienced haematuria. There were no significant differences in the length of stay in hospital, or intensive care units (ICU), or transfusion requirements or complications between groups. It is suggested that those who ski down the mountain themselves and present in a delayed fashion to medical/first aid facilities may still have serious abdominal injury but have a potentially higher rate of spleen salvage. PMID- 7868210 TI - Fractures of the facial skeleton in children. AB - Fractures of the facial skeleton in children are uncommon. This study presents the results of 139 children who sustained a total of 161 such fractures and were admitted to the Royal Hospital for Sick Children, Edinburgh, between January 1983 and December 1992. The male to female ratio was 3:1 and the highest incidence was at age 10 years. Analysis of fracture patterns showed that despite differences in anatomy, the fracture patterns were similar to those occurring in adults, but the relative proportion of each fracture type was different in children. Nasal fractures occurred most frequently (54 per cent), mandibular fractures constituted 30 per cent, and middle third fractures only 16 per cent. Falls, sporting injuries and road traffic accidents (RTA) were the major causes of these injuries. Injuries sustained in RTA were most likely to have involved cyclists or pedestrians in contrast to earlier series which have identified these injuries mainly among car passengers. No deaths were recorded and most patients made a complete recovery, although a few required secondary surgery for complications. This taken in conjunction with the findings of both high numbers of associated injuries, and increased severity commonly occurring in both mandibular and middle third injuries leads to the suggestion that these should be treated in centres where multidisciplinary management can easily be coordinated. PMID- 7868211 TI - Ultrasonographic appearance of external callus in long-bone fractures. AB - High-resolution real-time ultrasound (US) scanning was used to monitor serially 24 patients with an acute long-bone fracture and three patients with humeral non union, looking at the fracture site over a period of 12 months following the fracture. In both these groups, we found that US gave important information about the soft tissues surrounding the fracture site, and indicated callus formation at an early stage. US was more sensitive than conventional radiography at showing the early phases of organization of the callus, and its progression to bridging new bone formation. US also clearly showed a disorganized echopattern at the fracture site of the patients with non-union. PMID- 7868213 TI - Post-traumatic primary bacterial peritonitis. PMID- 7868212 TI - The epidemiology of major injuries in Mersey Region and North Wales. AB - A prospective epidemiological study was undertaken to determine the workload and patient characteristics for a putative trauma centre in a large defined area. One thousand and eighty-eight patients were included: 430 brought in dead, 309 hospital deaths and 349 survivors. Types of injury were: blunt 76 per cent, penetrating 3.6 per cent, burns 5.8 per cent, other 14 per cent. The incidence of blunt injury was 19/100,000 for patients arriving alive at hospital and accounted for 0.08 per cent of new A & E attendances. Eight per cent of blunt injury patients were children, 68 per cent were adults and 24 per cent elderly. Major causes of injury were: road accidents 67 per cent and falls 26 per cent. In patients arriving alive after blunt injuries, those who subsequently died were significantly older, more severely injured and more physiologically impaired. Hospital mortality was 45 per cent for blunt, 43 per cent for penetrating injuries, and 67 per cent for burns. TRISS methodology indicated 53 per cent of hospital deaths from blunt injuries were unexpected. Practically, it is questionable whether the incidence of major injuries is sufficient to provide the volume of patients necessary to sustain a Level I Trauma Centre. Nevertheless, concentration of injury service is essential, since no hospital receives sufficient patients to develop and maintain expertise. PMID- 7868214 TI - Late haemorrhage from the subclavian vein due to a fracture of the first rib. PMID- 7868215 TI - A new technique for the removal of a broken cannulated screw. PMID- 7868216 TI - Fracture of the maxilla following dog bite to the face. PMID- 7868217 TI - A case of survival of left atrial rupture caused by blunt chest injury. Is there a rapid diagnostic method? PMID- 7868218 TI - Non-union of a sacral fracture treated by bone graft and internal fixation. PMID- 7868219 TI - Hidden flexion injury of the cervical spine in ankylosing spondylitis. PMID- 7868220 TI - High substantial rupture of the anterior cruciate ligament in a 6-year-old boy. PMID- 7868221 TI - In vivo growth characteristics of leucine and methionine auxotrophic mutants of Mycobacterium bovis BCG generated by transposon mutagenesis. AB - Insertional mutagenesis in Mycobacterium bovis BCG, a member of the slow-growing M. tuberculosis complex, was accomplished with transposons engineered from the Mycobacterium smegmatis insertion element IS1096. Transposons were created by placing a kanamycin resistance gene in several different positions in IS1096, and the resulting transposons were electroporated into BCG on nonreplicating plasmids. These analyses demonstrated that only one of the two open reading frames was necessary for transposition. A library of insertions was generated. Southern analysis of 23 kanamycin-resistant clones revealed that the transposons had inserted directly, with no evidence of cointegrate formation, into different restriction fragments in each clone. Sequence analysis of nine of the clones revealed junctional direct 8-bp repeats with only a slight similarity in target sites. These results suggest that IS1096-derived transposons transposed into the BCG genome in a relatively random fashion. Three auxotrophs, two for leucine and one for methionine, were isolated from the library of transposon insertions in BCG. They were characterized by sequencing and found to be homologous to the leuD gene of Escherichia coli and a sulfate-binding protein of cyanobacteria, respectively. When inoculated intravenously into C57BL/6 mice, the leucine auxotrophs, in contrast to the parent BCG strain or the methionine auxotroph, showed an inability to grow in vivo and were cleared within 7 weeks from the lungs and spleen. PMID- 7868222 TI - Identification and characterization of a Mycoplasma hyopneumoniae adhesin. AB - An adhesin of Mycoplasma hyopneumoniae was identified and characterized in this study. A monoclonal antibody (MAb), F2G5, and its F(ab')2 fragments inhibited the adherence of M. hyopneumoniae to porcine tracheal cilia, the natural targets to which the mycoplasma binds during infection. MAb F2G5 detected multiple bands, but predominantly recognized a 97-kDa (P97) protein of M. hyopneumoniae on immunoblots. Affinity chromatography, conducted with immobilized MAb F2G5, mainly purified P97. The purified proteins were able to bind to cilia and blocked the adherence of intact M. hyopneumoniae cells to cilia. Immunolabeling of mycoplasmas with MAb F2G5 under electron microscopy demonstrated that the proteins recognized by MAb F2G5 were located at the surface of the mycoplasma, predominantly on a surface fuzzy layer. These results indicate that P97 functions as an adhesin of M. hyopneumoniae. The N-terminal amino acid sequence of P97 did not have significant homology with any known bacterial or mycoplasmal adhesins, suggesting that P97 is a novel protein. The predominant proteins detected by MAb F2G5 in different strains varied in size, indicating that the antigen bearing the epitope for MAb F2G5 undergo intraspecies size variation. Antigenic variation of adhesins may be a pathogenic mechanism utilized by M. hyopneumoniae to evade the porcine immune system. PMID- 7868223 TI - Isolation of Pasteurella haemolytica leukotoxin mutants. AB - Two mutants of Pasteurella haemolytica A1 that do not produce leukotoxin were isolated. Following mutagenesis, colonies were screened with antiserum by a filter assay for absence of the secreted leukotoxin. The two mutants both appeared to produce normal amounts of other antigens, as judged by reactivity with polyclonal serum from an animal with pasteurellosis, and were not altered in beta-hemolytic activity as seen on blood agar plates. There was no evidence of either cell-associated or secreted leukotoxin protein when Western blots (immunoblots) were carried out with the polyclonal serum or with a monoclonal antibody directed against the leukotoxin. Southern blots revealed that both mutants show the wild-type restriction pattern at the leukotoxin locus, although the strain with the lktA2 mutation showed differences in other regions of the chromosome on analysis by pulsed-field gel electrophoresis. The strain with the lktA2 mutation grew more slowly than did the wild-type strain, while the strain with the lktA1 mutation was indistinguishable from the wild-type strain in its growth properties. The strain with the lktA1 mutation should be valuable in determining the role of the leukotoxin in virulence as well as in identifying other virulence factors of P. haemolytica. PMID- 7868224 TI - Antigenic and virulence properties of Pasteurella haemolytica leukotoxin mutants. AB - Antigenic properties of two mutants of Pasteurella haemolytica, strains 59B0071 and 59B0072, that do not produce detectable leukotoxin were investigated. Western blot (immunoblot) analysis with a number of polyclonal sera from animals recovering from pasteurellosis revealed that both mutants secreted a variety of antigens that were also present in cultures of several wild-type strains. These antigens ranged from about 100 to 15 kDa. Mutant strain 59B0071 was found to be totally deficient in leukotoxin, as judged not only by Western blotting but also by cytotoxicity assays with bovine lymphoma (BL-3) cells or bovine polymorphonuclear cells as targets. The mutant strain 59B0071 had normal levels of a secreted sialylglycoprotease, however. When strains were tested for virulence in goat and cattle challenge experiments, a reduction in mortality and lung lesions was observed with the mutant 59B0071 in comparison with results obtained with wild-type strains. These results are consistent with an important role for leukotoxin in P. haemolytica virulence and suggest that leukotoxin negative mutants may be useful tools in the investigation of other virulence properties involved in P. haemolytica infections. PMID- 7868225 TI - Diphosphoryl lipid A from Rhodobacter sphaeroides transiently activates NF-kappa B but inhibits lipopolysaccharide induction of kappa light chain and Oct-2 in the B-cell lymphoma line 70Z/3. AB - Lipopolysaccharide (LPS) is implicated in much of the pathophysiology associated with gram-negative septic shock. One approach to this serious clinical problem is to develop new drugs that antagonize the action of toxic LPS. A model system to study LPS action and test for potential antagonists is readily provided by LPS regulation of the kappa gene in the murine B-cell line 70Z/3. Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA) effectively blocked toxic LPS induction of kappa light-chain immunoglobulin expression in 70Z/3 cells. Induction of kappa expression by LPS is dependent on the activation of at least two transcription factors, Oct-2 and NF-kappa B. RsDPLA completely repressed the long-term activation of NF-kappa B observed after 24 h of Salmonella typhosa LPS treatment and antagonized activation of oct-2 mRNA expression. However, RsDPLA was not an inert competitor of LPS. RsDPLA alone strongly activated NF-kappa B binding activity by 30 min but not beyond 9 h of treatment. It also induced a small increase in oct-2 mRNA levels. RsDPLA is not simply a weak agonist; we found no graded increase in kappa expression with increasing RsDPLA concentrations up to 50 micrograms/ml. The NF-kappa B complexes activated by RsDPLA and S. typhosa LPS were both composed of the p50-p65 heterodimer. These results suggest that the physiological LPS receptor(s) on B cells transmits qualitatively different signals depending on the nature of the binding ligand and that the fatty acyl groups of LPS play an important role in activating signal transduction. PMID- 7868226 TI - Infection of SCID mice with Mycobacterium leprae and control with antigen activated "immune" human peripheral blood mononuclear cells. AB - The SCID (severe combined immunodeficient) mouse lacks both B and T cells and tolerates injected mononuclear cells from humans, the principal hosts of Mycobacterium leprae. A SCID mouse model of leprosy could be useful to investigate potential vaccine strategies using human cells in a context in which the growth of the organism is monitored. Initial experiments determined that SCID mice are more susceptible than normal mice to infection and dissemination of M. leprae. Cells from humans, either BCG vaccinated or from countries where leprosy is endemic, were stimulated in vitro with a number of mycobacterial antigens- whole M. leprae, M. leprae cell walls, purified protein derivative of M. tuberculosis, and Mycobacterium bovis BCG--and tested for proliferation and production of interleukin-6, tumor necrosis factor alpha, and gamma interferon. Cell walls were the most efficient and consistent in inducing all of these activities. In vitro-activated human cells retain function better after injection into SCID mice than nonactivated cells. To test the ability of cells to affect the growth of M. leprae in the footpads of SCID mice, cells from a known responder to mycobacterial antigens and from a nonresponder were activated by M. leprae cell wall antigens. The cells were harvested and coinjected with fresh M. leprae into the right hind footpads of SCID mice. After 3 months, there was no growth of M. leprae in the footpads of mice coinjected with cells from the mycobacterial antigen responder, while growth was uninhibited in mice receiving cells from the nonresponder. Future experiments will determine requirements for antigen specificity in inhibiting M. leprae multiplication. PMID- 7868228 TI - Immunoglobulin G subclass response of juvenile periodontitis subjects to principal outer membrane proteins of Actinobacillus actinomycetemcomitans. AB - The cell envelope of Actinobacillus actinomycetemcomitans includes a number of outer membrane proteins (OMPs) which appear to be important targets for immunoglobulin G (IgG) antibodies in sera from localized juvenile periodontitis (LJP) patients. In this study, we examined the subclass distribution of IgG antibodies reactive to the 16.6- and 29-kDa OMPs of A. actinomycetemcomitans in sera from LJP patients and periodontally healthy individuals. Antibody responses were determined in a quantitative enzyme-linked immunosorbent assay that employed human IgG subclass-restricted monoclonal antibodies. High-titer LJP sera (93% black; geometric mean titer, 32,673) were found to contain significantly elevated levels of IgG1, IgG2, and IgG3 antibodies to the 29-kDa OMP of A. actinomycetemcomitans, compared with those of low-titer LJP sera (mean titer, 1,421) and sera from periodontally healthy, race-matched control subjects. The concentration of IgG2 antibody to this protein was greater than or equal to the corresponding IgG1 concentration in 7 of 14 high-titer sera, although mean IgG1 and IgG2 concentrations were not significantly different. The concentrations of IgG1 and IgG2 antibodies to the 16.6-kDa protein were also significantly elevated in LJP sera, although of considerably lesser magnitude than that observed for the 29-kDa protein. The IgG2 response to the 29-kDa protein could not be attributed to the presence of IgG2 antibodies to lipopolysaccharide contaminants or to Fc binding activity, nor does this molecule appear to be a glycoprotein. Hence, LJP subjects produce IgG2 antibodies, as well as IgG1 and IgG3 antibodies, directed to at least one of the major OMPs of A. actinomycetemcomitans. PMID- 7868227 TI - Molecular analysis of the plasmid-encoded hemolysin of Escherichia coli O157:H7 strain EDL 933. AB - In this study, we determined the nucleotide sequence of the 5.4-kb SalI restriction fragment of the recombinant plasmid pEO40-1, cloned from the large plasmid of enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain EDL 933. This revealed two open reading frames which shared approximately 60% homology to the hlyC and hlyA genes of the E. coli alpha-hemolysin (alpha-hly) operon. We termed these genes EHEC-hlyA and EHEC-hlyC to distinguish them from the alpha-hly genes. Preliminary sequence analysis indicated that another open reading frame homolog to the hlyB gene is located close to the 3' end of EHEC-hlyA. The predicted molecular masses of the EHEC-hlyA and EHEC-hlyC gene products were 107 and 19.9 kDa, respectively. The EHEC hemolysin protein (EHEC-Hly) was not secreted into the culture supernatant by the strain EDL 933. However, hemolytic activity was found in the broth culture supernatant after transforming EDL 933 with the recombinant plasmid pRSC6 carrying the hlyB and hlyD genes from the E. coli alpha hemolysin operon. The EHEC hemolysin was precipitated and used as an antigen for immunoblot analysis. This demonstrated that 19 of 20 reconvalescent-phase serum samples from patients with hemolytic uremic syndrome reacted specifically with the antigen; conversely, only 1 of 20 control serum samples demonstrated reactivity. To investigate the prevalence of EHEC hemolysin genes in diarrheagenic E. coli, a PCR was developed to specifically detect EHEC-hlyA. All Shiga-like toxin-producing O157 strains and 12 of 25 Shiga-like toxin-producing non-O157 strains were PCR positive; strains of other categories of diarrheagenic E. coli were PCR negative. All PCR-positive strains hybridized with the CVD 419 probe. We found the CVD 419 probe to be identical to the 3.4-kb HindIII fragment of plasmid pEO40 carrying most of the EHEC-hlyA gene and a part of the putative EHEC-hlyB gene. In this study, the newly discovered EHEC hemolysin was shown to be responsible for the enterohemolytic phenotype and demonstrated to be related but not identical to alpha-hemolysin. The EHEC hemolysin appears to have clinical importance because it occurs in all O157 strains tested and is reactive to sera of patients with hemolytic uremic syndrome. PMID- 7868229 TI - Immunoglobulin G2 antibodies promote neutrophil killing of Actinobacillus actinomycetemcomitans. AB - Sera from patients with localized juvenile periodontitis (LJP) often contain markedly elevated levels of immunoglobulin G2 (IgG2) antibodies reactive to cell envelope constituents of Actinobacillus actinomycetemcomitans. The objective of this study was to determine if these IgG2 antibodies are capable of supporting phagocytosis and killing of A. actinomycetemcomitans by human neutrophils. Polyclonal IgG2 antibodies were prepared from high-titer LJP serum by affinity chromatography, yielding a preparation which was > 99% subclass restricted and retained immunoreactivity to A. actinomycetemcomitans antigens. Affinity-purified IgG2 antibodies were evaluated by an in vitro opsonophagocytic assay that employed neutrophils obtained from donors who were homozygous for the H131 allotype of Fc gamma receptor type IIa (CD32), which efficiently binds human IgG2 antibodies. Affinity-purified IgG2 antibodies from LJP serum but not from sera of periodontally healthy individuals promoted phagocytosis and killing of A. actinomycetemcomitans. The expression of IgG2-dependent opsonic activity required the presence of complement. Incubation of A. actinomycetemcomitans with neutrophils in the presence of an optimal concentration of LJP IgG2 (50 micrograms/ml) and 5% hypogammaglobulinemic serum (as a complement source) resulted in a > 1 log10 reduction in bacterial viability within 30 min. The opsonic activity of IgG2 antibodies was found to be comparable to that observed with affinity-purified IgG1 antibodies. Moreover, IgG1 antibodies interacted synergistically with IgG2 antibodies in promoting opsonophagocytosis of A. actinomycetemcomitans. The results of this study indicate that LJP serum contains IgG2 antibodies which, when employed in conjunction with neutrophils that express Fc gamma receptors capable of recognizing this subclass, are opsonic for A. actinomycetemcomitans. PMID- 7868230 TI - In vivo induction of interleukin-12 mRNA expression after oral immunization with Salmonella dublin or the B subunit of Escherichia coli heat-labile enterotoxin. AB - Mice orally immunized with Salmonella dublin EL23, a nonreverting, aromatic dependent, histidine-requiring mutant transformed with a plasmid which carries a gene that codes for production of the B subunit of the heat-labile toxin (LT-B) of enterotoxigenic Escherichia coli, or with purified LT-B alone were compared for their ability to initiate expression of interleukin-12 (IL-12) mRNAs at mucosal sites. At 6 or 20 h following oral immunization, the Peyer's patches and mesenteric lymph nodes were removed, and polyadenylated mRNA was prepared from each tissue. Constitutive expression of an mRNA encoding the p35 subunit of IL-12 was observed in control as well as immunized mice. Conversely, expression of an mRNA encoding the p40 subunit of IL-12 was not detected in control animals but was dramatically upregulated in immunized mice. By using semiquantitative reverse transcription-PCR (RT-PCR) followed by competitive RT-PCR, differences in the magnitude of IL-12 p40 mRNA expression were quantified. Six hours after oral immunization with the Salmonella construct, mice had 12.1- and 8.4-fold increases in expression of IL-12 p40 mRNA in the Peyer's patches and mesenteric lymph nodes, respectively, compared with control mice receiving only saline. By 20 h, the pattern of increased mRNA expression was reversed, showing 2.5- and 17.6-fold increases in the Peyer's patches and mesenteric lymph nodes, respectively. Oral immunization with LT-B alone also stimulated IL-12 p40 mRNA expression, but to a lesser extent. The constitutive expression of IL-12 p35 mRNA at these mucosal sites coupled with a rapid and dramatic induction of IL-12 p40 mRNA following immunization with wild-type or attenuated strains of S. dublin is consistent with other investigations which support a role for IL-12 in modulating cell-mediated immune responses against intracellular pathogens. PMID- 7868231 TI - Altered expression of the platelet aggregation-associated protein from Streptococcus sanguis after growth in the presence of collagen. AB - Certain strains of Streptococcus sanguis adhere selectively to human platelets (Adh+) and, in plasma, induce them to aggregate into in vitro thrombi (Agg+). The induction of aggregation is mediated by the platelet aggregation-associated protein (PAAP) expressed on the cell surface of the streptococcus. In endocarditis, expression of PAAP may be regulated by association with host proteins on damaged heart valves. To begin to test this hypothesis, three strains of S. sanguis were each cultured in the presence or absence of collagens (types I to X), laminin, or PAAP-derived peptide preparations. After harvesting and washing, the platelet-interactive phenotype of strains 133-79 (Adh+ Agg+), L74 (Adh+ Agg-), and 10556 (Adh- Agg-) was unchanged. The cells from each culture were then digested mildly with trypsin to isolate PAAP. PAAP isolated from strain 133-79 (Adh+ Agg+) grown in the absence of added collagen, other proteins, or peptides inhibited platelet aggregation in response to untreated cells of S. sanguis. Platelet aggregation was induced immediately, however, by PAAP from strain 133-79 isolated after growth in the presence of 300 nM type I collagen, while lower concentrations yielded protein fragments that potentiated the response to intact cells. Aggregation-inducing PAAP could be removed by anti-PAAP (PGEQGPK) immunoaffinity chromatography, but only inhibitory activity could be recovered. The agonist effect of PAAP was not associated with collagen itself, since the PAAP preparations did not contain detectable amounts of hydroxyproline. PAAP antigens isolated from cells grown in the presence and absence of collagen had similar apparent molecular weights, as estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western immunoblotting. When electrophoresis was performed under nondenaturing conditions, however, PAAP isolated from cells grown in type I collagen migrated more slowly. Strain L74 grown with type I collagen yielded tryptic fragments of proteins that inhibited aggregation significantly better than control peptides (no collagen in the medium). Strain 10556 was apparently unaffected by growth in type I collagen. The effect of type I collagen was somewhat unique. Growth in the presence of collagen types II to VI (300 nM) yielded protein fragments that potentiated without inducing platelet aggregation, while other collagens, laminin, and PAAP-derived peptides did not affect platelet aggregation. These results suggest that growth in the presence of type I collagen and, perhaps, collagens II to VI alters the expression and conformation of PAAP in certain strains of S. sanguis. PMID- 7868232 TI - Entamoeba histolytica suppresses gamma interferon-induced macrophage class II major histocompatibility complex Ia molecule and I-A beta mRNA expression by a prostaglandin E2-dependent mechanism. AB - The surface expression of class II major histocompatibility complex immune associated (Ia) antigen is a principal accessory function of macrophages for antigen-specific T-cell activation and immunoregulation. To explore the mechanisms of impaired cell-mediated immunity in invasive amebiasis, we investigated the effects of Entamoeba histolytica proteins on gamma interferon (IFN-gamma)-induced Ia expression by murine bone marrow-derived macrophages. Pretreatment of macrophages with secreted (conditioned medium) or whole soluble amebic proteins inhibited the induction of IFN-gamma-induced surface Ia antigen expression by 30 to 61% but had no effect on surface Ia molecules already expressed. By Northern (RNA) blot analysis, amebic proteins suppressed IFN-gamma induced macrophage I-A beta mRNA accumulation by 36% but did not alter the constitutive levels of actin mRNA expression. E. histolytica stimulated macrophages to produce high levels of prostaglandin E2 (PGE2) as determined by reverse-phase high-pressure liquid chromatography and quantification by PGE2 specific radioimmunoassay. Inhibition of PGE2 biosynthesis with the cyclooxygenase inhibitor indomethacin abrogated ameba-induced suppression of Ia antigen by 60%, whereas exogenously added PGE2 decreased IFN-gamma-induced macrophage Ia expression by 44%. Our results suggest that the mechanism whereby E. histolytica suppresses IFN-gamma-induced macrophage surface Ia molecule synthesis and I-A beta mRNA expression is by stimulating the production of PGE2, which acts in an autocrine fashion for immunoregulation. E. histolytica subverting critical macrophage accessory function via PGE2 biosynthesis is a novel strategy which the parasite uses to suppress host defenses. PMID- 7868233 TI - Helicobacter pylori-specific CD4+ T-cell clones from peripheral blood and gastric biopsies. AB - Colonization of human gastric mucosa with cytotoxic strains of the bacterium Helicobacter pylori is associated with peptic ulcer and with chronic gastritis. Since little is known about the T-cell response to H. pylori, we investigated the CD4+ T-cell response both in peripheral blood mononuclear cells (PBMCs) and at the site of infection. First, we compared the bulk PBMC proliferative response to the bacterium in individuals with and without symptoms of gastroduodenal disease. We found that the PBMCs from virtually all individuals proliferate in response to heat-inactivated bacteria. Second, we cloned H. pylori-specific CD4+ T lymphocytes from the PBMCs of three patients and from both the gastric mucosa and PBMCs of a fourth patient. We have found that CD4+ T-cell clones specific for H. pylori from peripheral blood samples and gastric mucosae of infected patients are major histocompatibility complex class II restricted and discriminate between several cytotoxic and noncytotoxic bacterial strains. Moreover, they are polyclonal in terms of T-cell receptor usage and major histocompatibility complex restriction. Our results demonstrate that the T-cell response to the whole bacterium in PBMCs does not correlate with antibody response, infection, or disease. However, H. pylori-specific CD4+ T cells are detectable, at the clonal level, in both the periphery and gastric mucosa of infected patients. Localization of these cells at the site of disease suggests they are effectors of the immune response to the bacteria. PMID- 7868234 TI - TH1 cells trigger tumor necrosis factor alpha-mediated hypersensitivity to Pseudomonas aeruginosa after adoptive transfer into SCID mice. AB - Recent experiments have shown that gamma interferon (IFN-gamma), either administered or induced in vivo, e.g., by certain bacteria, is a key mediator in inducing hypersensitivity to bacterial lipopolysaccharides. The source of endogenous IFN-gamma in this context (natural killer versus TH1 cells) has not been investigated yet. In order to investigate the role of antigen-specific, IFN gamma-producing TH1 cells in murine Pseudomonas aeruginosa infection, a murine TH1 cell line was propagated in vitro by using recombinant P. aeruginosa outer membrane protein I. Adoptive transfer experiments were performed by intravenous injection of various amounts of TH1 cells into P. aeruginosa-challenged SCID mice. Adoptive transfer of 5 x 10(6) T cells into SCID mice followed by an intraperitoneal challenge with 1.4 x 10(6) CFU of live P. aeruginosa resulted in the rapid death of the animals within 12 h postchallenge, whereas transfer of lower T-cell doses and saline as a control did not cause any detrimental effects. After challenge with 2.8 x 10(6) CFU of P. aeruginosa, similar results were obtained 18 h postchallenge; however, at the end of the 72-h observation period, no significant differences in survival rates were obtained between the groups treated with different amounts of T cells. The rapid death of mice treated with 5 x 10(6) T cells was reflected by 860-fold-elevated levels of tumor necrosis factor alpha (TNF-alpha) present in serum 2 h postchallenge, whereas no significant differences in TNF-alpha serum levels were detectable in mice treated with lower doses of T cells or with saline. Pretreatment of T-cell-reconstituted SCID mice with neutralizing anti-IFN-gamma monoclonal antibodies completely protected mice from bacterial challenge and reduced TNF-alpha levels in serum. We conclude that under the experimental conditions described here, IFN-gamma- and interleukin-2-producing TH1 cells represent an important trigger mechanism inducing TNF-alpha-mediated hypersensitivity to bacterial endotoxin. PMID- 7868235 TI - Helicobacter-associated gastritis in SCID mice. AB - Immunodeficient (SCID) and immunocompetent mice were infected with Helicobacter felis to address the role of autoimmunity in Helicobacter-associated gastritis. The extents of inflammation were equivalent in the two groups. The numbers of H. felis organisms were marginally increased in the SCID mice but did not achieve statistical significance. These results indicate that autoimmunity is not necessary to induce disease and that the presence of an adaptive immune system does not significantly affect H. felis colonization. PMID- 7868236 TI - Lipopolysaccharide-induced apoptosis in swine lymphocytes in vivo. AB - The in vivo effects of bacterial lipopolysaccharide (LPS) on the immune systems of piglets were investigated. Intravenous injection of 0.5 mg of LPS per kilogram of body weight induced apoptosis, which was characterized by nuclear chromatin condensation and fragmentation and a ladder formation of nucleosomal DNA in lymphocytes both in the cortex of the thymus and in the germinal centers and paracortical areas of mesenteric lymph nodes at 24 h postinjection. The levels of endotoxin, tumor necrosis factor alpha, and cortisol in serum increased, generally according to the dose of LPS. These findings suggest that LPS can induce in vivo apoptosis of lymphocytes in piglets and support the notion that cytokine and endocrine responses may play an important role in LPS-induced apoptosis in the immune system. PMID- 7868237 TI - Expression of a nonagglutinating fimbria by Proteus mirabilis. AB - We have clarified growth conditions and isolation strategies for the nonagglutinating fimbriae from Proteus mirabilis. Nonagglutinating fimbriae were expressed by all P. mirabilis strains we examined, and the major subunit proteins, which ranged from 23 to 29 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, had highly conserved N-terminal sequences. PMID- 7868238 TI - Interleukin-10 downregulates protective immunity to Brucella abortus. AB - In vivo neutralization of interleukin-10 (IL-10) with an anti-IL-10 monoclonal antibody resulted in up to 10-fold fewer bacteria in the spleens of BALB/c mice infected with the virulent Brucella abortus strain 2308. In vitro neutralization of endogenous IL-10 in brucella antigen-stimulated cultures of splenocytes from infected mice resulted in increased gamma interferon production in these cultures, whereas exogenous recombinant IL-10 inhibited the ability of peptone elicited peritoneal macrophages to control intracellular brucellae. These data suggest that IL-10 may be downregulating the immune response to B. abortus by affecting both macrophage effector function and the production of the protective Th1 cytokine gamma interferon. PMID- 7868239 TI - Cholera toxin and Salmonella typhimurium induce different cytokine profiles in the gastrointestinal tract. AB - Salmonella infection of the gastrointestinal tract (GT) results in fluid secretion and inflammation. In contrast, cholera toxin (CT) induces fluid secretion but no inflammation. Using a murine ligated intestinal loop model, we investigated cytokine production (interleukin-1 [IL-1], IL-2, IL-4, IL-6, IL-10, gamma interferon, and tumor necrosis factor alpha) in the GT following exposure to these agents. Salmonella typhimurium induced a Th1-like cytokine profile in loops obtained from either nonimmune mice or Salmonella-immunized mice. CT induced only IL-6 and IL-10 production in ligated loops from nonimmune mice but induced a Th2-like cytokine profile in ligated loops obtained from CT-immunized mice. These results show that CT and S. typhimurium induce very different cytokine profiles in the GT. PMID- 7868241 TI - Nitric oxide production does not directly increase macrophage candidacidal activity. AB - Some activated murine macrophages produced nitrite but were unable to kill Candida albicans. Furthermore, a nitric oxide (NO) generator inhibited C. albicans growth but was not candidacidal. Our results suggest that NO is candidastatic and that No is not directly involved but is associated with or induces other macrophage candidacidal mechanisms. PMID- 7868240 TI - Globotriaosylceramide, Gb3, is an alternative functional receptor for Shiga-like toxin 2e. AB - We reexamined the binding specificity of the Shiga-like toxin variant associated with porcine edema disease, SLT2e, which is reported to be more cytotoxic for Vero cells than for HeLa cells, by using receptor-deficient cells and a liposomal insertion system for purified glycolipids. We found that SLT2e preferentially uses globotetraosylceramide as a receptor but can also cause cytotoxicity by using globotriaosylceramide, the SLT2 receptor. We conclude that the differential cytotoxicity of SLT2e on HeLa and Vero cells is a function of both the receptor preference of the toxin and the specific glycolipid content of the target cells being used. PMID- 7868242 TI - Involvement of 5-hydroxytryptamine and prostaglandin E2 in the intestinal secretory action of Escherichia coli heat-stable enterotoxin B. AB - The intestinal secretory action of Escherichia coli heat-stable enterotoxin B (STb) is poorly defined. Previous work indicates that STb causes loss of intestinal fluid and electrolytes by a mechanism independent of elevated levels of cyclic nucleotides, the hallmark of other E. coli cytotonic enterotoxins. In the work described in this report, we observed that treatment of ligated rat intestinal loops with purified STb of E. coli resulted in a dose-dependent rise in intestinal secretion concomitant with dose-related increases in levels of serotonin (5-hydroxytryptamine [5-HT]) and prostaglandin E2 (PGE2). Treatment of rats with the 5-HT2 receptor antagonist ketanserin prior to STb challenge resulted in significant (P < 0.05) reduction in intestinal secretion. Blockage of 5-HT2 receptors with ketanserin also reduced (P < 0.05) the level of PGE2 observed following STb treatment, indicating that at least a portion of the PGE2 was formed in response to 5-HT2 receptor stimulation. In a similar fashion, indomethacin, an inhibitor of cyclooxygenase activity, significantly reduced the level of secretion (P < 0.05) observed following STb treatment yet had no effect on 5-HT levels. Treatment of rats with both ketanserin and indomethacin further reduced STb-mediated secretion to a level not attained by either drug alone. Taken together, our data suggest that secretion due to STb involves both 5-HT and PGE2 as intestinal secretagogues. Furthermore, PGE2 formation appears to arise through both 5-HT-dependent and 5-HT-independent pathways. PMID- 7868243 TI - Roles of gamma interferon and other cytokines in suppression of the spleen cell proliferative response to concanavalin A and toxoplasma antigen during acute toxoplasmosis. AB - Suppressed splenocyte proliferation in response to mitogen and toxoplasma lysate antigen (TLA) is observed in mice acutely infected with Toxoplasma gondii. Recently, we reported that NG-monomethyl-L-arginine (NMMA), an inhibitor of reactive nitrogen intermediate (RNI) production, partially restored proliferative responses of splenocytes from infected mice. In the present study we have examined the effect of NMMA on production of cytokines by splenocytes from mice acutely infected with T. gondii and assessed the role of gamma interferon (IFN gamma) and interleukin-10 (IL-10) in the RNI-mediated suppression. Stimulation with concanavalin A (ConA) or TLA of splenocytes from CBA/Ca mice infected for 7 days resulted in increased production of IFN-gamma, IL-4, and IL-10 but reduced levels of IL-2 when compared with cultures of splenocytes from uninfected mice. Whereas addition of NMMA did not alter levels of cytokines produced by splenocytes from uninfected mice, splenocytes from infected mice stimulated with ConA produced significantly higher levels of IL-10 and reduced levels of IL-2 and IL-4. Addition of anti-IFN-gamma monoclonal antibodies to cultures of spleen cells from mice infected for 7 or 14 days remarkably decreased the levels of nitrite and resulted in a 47- and 4-fold increase in proliferation induced by stimulation with ConA or TLA, respectively. Anti-IL-10 did not reduce levels of nitrite produced in culture but did result in a fourfold increase in the proliferative response of splenocytes from mice infected for 14 days. In vivo administration of anti-IFN-gamma or anti-IL-10 monoclonal antibodies to infected mice partially restored ex vivo spleen cell proliferative responses by approximately 40 and 15%, respectively. Our data indicate that IFN-gamma is important in inducing the RNI-mediated immunosuppression, which, in turn, affects production of cytokines by splenocytes. Our data also demonstrate that IL-10 is involved in the suppression observed but that this activity is independent of RNI. PMID- 7868244 TI - Relationship between colonial morphology and adherence of Streptococcus pneumoniae. AB - Phase variants in colonial opacity of pneumococci differ in the ability to colonize the nasopharynx of infant rats. To explain this observation at a cellular level, we compared the ability of opacity variants to adhere to buccal epithelial cells, type II pneumocytes, or vascular endothelial cells and to the glycoconjugates that represent the cognate receptors at each of these sites. The transparent phenotype was associated with enhanced adherence to buccal cells (approximately 100%) and their receptor relative to that of the opaque variants. Only modest differences in adherence (< 45%) were demonstrated to resting lung and vascular cells. In contrast, adherence of transparent variants increased by 90% to lung cells stimulated with interleukin-1 and by 130% to endothelial cells stimulated with tumor necrosis factor. In contrast, cytokine stimulation did not influence the adherence of opaque pneumococci. This difference correlated with the unique ability of transparent variants to adhere to immobilized GlcNAc and to cells bearing transfected platelet-activating factor receptors. These results suggest that the mechanism of enhanced colonization of the nasopharynx in vivo by transparent as compared with opaque phase variants involves a greater ability to adhere to both GlcNAc beta 1-3Gal on buccal epithelial cells and GlcNAc and PAF receptors on cytokine-activated, as opposed to resting, lung and endovascular cells. PMID- 7868245 TI - Biological and genetic characterization of TnphoA mutants of Salmonella typhimurium TML in the context of gastroenteritis. AB - TnphoA transposon insertion mutants of phoN-negative derivatives of Salmonella typhimurium TML (of human gastroenteritic origin) were selected by growing mutagenized recipient bacteria under a variety of growth conditions. Ninety-seven individual mutants, which expressed alkaline phosphatase, were collected and tested for their ability to invade HEp-2 cells. Seven smooth mutants had a reduced ability to invade HEp-2 cells, and three smooth mutants were consistently more invasive than their corresponding parental strains. One rough mutant was of similar invasiveness and two were of reduced invasiveness when compared with that of parental strains. The seven smooth hypoinvasive mutants, the three smooth hyperinvasive mutants, and the three rough mutant strains were tested for their abilities to invade ileal enterocytes by the rabbit ileal invasion assay described previously (3). All smooth mutants exhibited parental levels of invasiveness. The rough mutants were hypoinvasive in the rabbit ileal invasion assay. The HEp-2 system is therefore not a good predictor of behavior in gut tissue in this model. DNA sequences flanking the transposon were determined for five mutants which were hypoinvasive in the HEp-2 cell assay. The mutations were found to be insertions in two previously identified invasion genes, invG and invH, and in a gene not normally associated with invasion, pagC. These observations lead one to be cautious in the interpretation of the biological significance of data obtained from invasion of tissue culture monolayers when extrapolated to gut tissue. PMID- 7868246 TI - Intravascular cryptococcal culture filtrate (CneF) and its major component, glucuronoxylomannan, are potent inhibitors of leukocyte accumulation. AB - Disseminated cryptococcosis is characterized by high titers of cryptococcal polysaccharides in serum and minimal cellular infiltrates in infected tissues of patients. The main objective of this study was to determine whether the circulating cryptococcal polysaccharides could contribute to the lack of cellular infiltration into infected tissues. To assess this possibility, a gelatin sponge implantation model was used. We found that intravenous (i.v.) injection of mice with cryptococcal culture filtrate antigen (CneF) inhibited migration of leukocytes (neutrophils, lymphocytes, and monocytes) into the intrasponge sites of acute inflammation induced by CneF, tumor necrosis factor alpha, or formylmethionyl leucyl phenylalanine. In addition, i.v. administration of CneF inhibited leukocyte migration into the intrasponge sites of a cell-mediated immune reaction irrespective of whether the delayed-type hypersensitivity response was to CneF or the mycobacterial antigen purified protein derivative. Glucuronoxylomannan, a major constituent of CneF and a major cryptococcal antigen detected in the sera of patients with disseminated cryptococcosis, when given i.v. to mice, inhibited leukocyte migration into the sponges. Our results suggest that the minimal cellular infiltrates observed in infected tissues of cryptococcosis patients may be due, in part, to the circulating cryptococcal polysaccharide functioning as we have demonstrated in the mouse model. Furthermore, the high titers of cryptococcal antigen in the sera of patients may diminish leukocyte migration in response to stimuli other than Cryptococcus neoformans, a point that may be relevant in AIDS patients with cryptococcosis. PMID- 7868247 TI - Pneumocystis carinii glycoprotein A binds macrophage mannose receptors. AB - Pneumocystis carinii causes life-threatening pneumonia in patients with impaired immunity. Recent studies suggest that alveolar macrophages interact with P. carinii through macrophage mannose receptors. However, the ligand(s) on P. carinii that is recognized by these receptors has not been fully defined. P. carinii contains a major mannose-rich surface antigen complex termed glycoprotein A (gpA). It was therefore hypothesized that gpA binds directly to macrophage mannose receptors and mediates organism attachment to these phagocytes. To assess this, gpA was purified from P. carinii by continuous-elution gel electrophoresis. 125I-labeled gpA bound to alveolar macrophages in a saturable fashion. In addition, gpA binding was substantially inhibited by both alpha-mannan and EDTA, further suggesting that gpA interacts with macrophage mannose receptors. Macrophage membrane proteins capable of binding to gpA were isolated with a gpA Sepharose column. A 165-kDa membrane-associated protein was specifically eluted from the gpA-Sepharose column with EDTA (20 mM). This protein was identified as the macrophage mannose receptor by immunoprecipitation with a polyclonal anti mannose receptor antiserum. To further investigate the role of gpA in P. carinii macrophage interactions, 51Cr-labeled P. carinii cells were incubated with macrophages in the presence of increasing concentrations of soluble gpA, and organism attachment was quantified. Soluble gpA (2.5 mg/dl) competitively inhibited P. carinii attachment to alveolar macrophages by 51.3% +/- 3.7% (P = 0.01). Our findings demonstrate that gpA present on P. carinii interacts directly with mannose receptors, thereby mediating organism attachment to alveolar macrophages. PMID- 7868248 TI - Immunopathological activities of extracellular products of Streptococcus mitis, particularly a superantigenic fraction. AB - Previously, we prepared extracellular products, fractions F-1 and F-2 of Streptococcus mitis 108, an isolate from the tooth surface of an infant, and showed that F-1 exhibited inflammatory cytokine-inducing activities. In the present study, we present evidence that fraction F-2 induced human T-cell proliferation in the presence of irradiated human peripheral blood mononuclear cells and selectively activated T cells bearing V beta 2 and V beta 5.1 in the T cell receptor. F-1, on the other hand, stimulated human gingival fibroblasts to support the T-cell proliferation in the same way as human gamma interferon or Prevotella intermedia lipopolysaccharide (LPS). Fraction F-1 also primed gingival fibroblasts to support the production of interleukin-2 and gamma interferon by the T cells upon stimulation with F-2. Human gingival fibroblasts stimulated with fraction F-1, like those stimulated by P. intermedia LPS and human gamma interferon, exhibited human leukocyte antigen (HLA)-DR mRNA expression and cell surface HLA-DR molecules as detected by enzyme-linked immunosorbent assay. An anti-HLA-DR monoclonal antibody inhibited T-cell proliferation in response to F 2, probably through inactivating the accessory function of HLA-DR-bearing fibroblasts. T cells activated with F-2 in the presence of irradiated peripheral blood mononuclear cells exhibited definite cytotoxic effects against fibroblasts and squamous carcinoma cells originating from human oral tissues. These findings are strongly suggestive of an association of extracellular products of viridans streptococci with pathogenesis of oral mucosal diseases, particularly those disorders in gingiva which are accompanied by heavy infiltration of T cells. PMID- 7868249 TI - Secretion of human interleukin 2 by recombinant Mycobacterium bovis BCG. AB - The human interleukin 2 (huIL-2) gene was introduced into Mycobacterium bovis BCG by using the integrative vector pMV306. To express and secrete huIL-2 from BCG, two different plasmids, CI and CII, were made. In CI, the huIL-2-encoding region was under the control of the alpha-antigen promoter of BCG; in CII, the expression of huIL-2 was regulated by the heat shock protein 60 promoter. A signal peptide sequence isolated from the naturally secreted alpha-antigen of BCG was inserted between the promoter and huIL-2-encoding region to facilitate secretion. Both huIL-2 expression plasmids were integrated into the BCG genome when introduced into the BCG Pasteur strain by electroporation. Approximately 150 U of huIL-2 was secreted into the medium of a BCG-CII culture, while the BCG-CI cells secreted approximately one-sixth of that amount. When the IL-2-expressing BCG strain BCG-CII was injected intravenously into BALB/c mice, the number of BCG cells in the spleens of these mice was significantly less than the number in the control mice. The decreased number of IL-2-expressing BCG cells is likely due to the augmentation of the host immune response by the secreted huIL-2, although the exact mechanism is not known. PMID- 7868250 TI - Guinea pig cellular immune responses to proteins secreted by Mycobacterium tuberculosis. AB - To study the immunological activity of proteins secreted by Mycobacterium tuberculosis, we carried out comparative studies in guinea pigs infected intravenously with 2.5 x 10(3) CFU of this organism or with 2.5 x 10(4) CFU of Mycobacterium bovis BCG. Groups of infected guinea pigs were skin tested with fractions of secreted proteins covering well-defined narrow-molecular-mass regions, or such fractions were used for lymphocyte stimulation experiments. The lymphocyte stimulation experiments showed that the fraction containing proteins with molecular masses below 10 kDa had a superior stimulating capacity in tuberculous guinea pigs whereas the 24- to 30-kDa fraction gave significantly higher skin reactions in this group compared with BCG-vaccinated guinea pigs. A precise mapping within the region from 23 to 35 kDa by using a combination of narrow overlapping fractions and purified proteins enabled the identification of the 24-kDa antigen MPT64 as a molecule specific for tuberculous infection. Thus, MPT64 is a promising candidate for a specific diagnostic skin test reagent for human tuberculosis. PMID- 7868251 TI - A 37-kilodalton glycoprotein of Babesia divergens is a major component of a protective fraction containing low-molecular-mass culture-derived exoantigens. AB - The supernatants of in vitro cultures of Babesia divergens Rouen 1987 in human erythrocytes, obtained by using a semidefined medium based on human high-density lipoproteins, were fractionated by gel filtration chromatography into four fractions, F1 to F4. The crude supernatant as well as each fraction adjuvanted with Quil-A protected gerbils from mortality due to a homologous infectious challenge. Analysis of the humoral response of the 10 protected gerbils with fraction F4, containing major proteins with molecular masses lower than 50 kDa, showed that a few antigens (from 50 to 17 kDa) could be important candidates for an improved vaccine against B. divergens babesiosis. As an immunodominant response was directed against the 37-kDa antigen (Bd37) in two different B. divergens strains tested, a polyclonal antibody directed against Bd37 was produced in a rabbit. In an immunofluorescence assay, the anti-Bd37 antiserum strongly labelled small internal vesicles of the merozoites and the cell surface was diffusely labelled after fixation, whereas on live merozoites, this labelling was not observed. [3H]glucosamine-radiolabelling experiments demonstrate that Bd37 is a glycoprotein. The Bd37 protein can also be labelled with [14C]palmitate but not with [3H]myristic acid. In Triton X-114 temperature phase partitioning of B. divergens-infected erythrocyte extracts, Bd37 was exclusively found into the detergent phase, indicating that the palmitoylated Bd37 protein was in the membrane fraction. In the in vitro supernatant, the glycoprotein Bd37 was found in a nonpalmitoylated form, indicating excretion and/or release of the glycoprotein from the merozoite. PMID- 7868252 TI - Molecular cloning and characterization of the nontypeable Haemophilus influenzae 2019 rfaE gene required for lipopolysaccharide biosynthesis. AB - The lipooligosaccharide (LOS) of nontypeable Haemophilus influenzae (NTHi) is an important factor in pathogenesis and virulence. In an attempt to elucidate the genes involved in LOS biosynthesis, we have cloned the rfaE gene from NTHi 2019 by complementing a Salmonella typhimurium rfaE mutant strain with an NTHi 2019 plasmid library. The rfaE mutant synthesizes lipopolysaccharide (LPS) lacking heptose, and the rfaE gene is postulated to be involved in ADP-heptose synthesis. Retransformation with the plasmid containing 4 kb of NTHi DNA isolated from a reconstituted mutant into rfaE mutants gave wild-type LPS phenotypes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis confirmed the conversion of the rfaE mutant LPS to a wild-type LPS phenotype. Sequence analysis of a 2.4-kb BglII fragment revealed two open reading frames. One open reading frame encodes the RfaE protein with a molecular weight of 37.6 kDa, which was confirmed by in vitro transcription and translation, and the other encodes a polypeptide highly homologous to the Escherichia coli HtrB protein. These two genes are transcribed from the same promoter region into opposite directions. Primer extension analysis of the rfaE gene revealed a single transcription start site at 37 bp upstream of the predicted translation start site. The upstream promoter region contained a sequence (TA AAAT) homologous to the -10 region of the bacterial sigma 70-dependent promoters at an appropriate distance (7 bp), but not sequence resembling the consensus sequence of the -35 region was found. These studies demonstrate the ability to use complementation of defined LPS defects in members of the family Enterobacteriaceae to identify LOS synthesis genes in NTHi. PMID- 7868253 TI - Pertussis toxin-mediated ADP-ribosylation of target proteins in Chinese hamster ovary cells involves a vesicle trafficking mechanism. AB - Pertussis toxin (PT)-catalyzed ADP-ribosylation of target proteins in intact Chinese hamster ovary (CHO) cells was evaluated with an in vitro ADP-ribosylation assay. In this assay, a postnuclear supernatant was prepared from CHO cells and used as a source of PT-sensitive target proteins for in vitro [32P[ADP ribosylation. The postnuclear supernatant contained three proteins that were ADP ribosylated in vitro, with apparent molecular masses of 50, 45, and 42 kDa. The 42- and 45-kDa proteins were membrane associated, while the 50-kDa protein was soluble. Following PT treatment of CHO cells, the 42- and 45-kDa proteins were not available for in vitro ADP-ribosylation, while the soluble 50-kDa protein remained available for in vitro ADP-ribosylation. The decrease in the availability of the 42- and 45-kDa proteins to in vitro ADP-ribosylation was proportional to the PT concentration and time of incubation with CHO cells. Western immunoblot analysis showed that extracts from PT-treated CHO cells and control CHO cells possessed equivalent amounts of two proteins that were recognized by anti-Gi protein antiserum. The two proteins recognized by anti-Gi protein antiserum from PT-treated cells migrated with higher apparent molecular weights than the two proteins from control cells. This was consistent with the in vivo ADP-ribosylation of the two proteins by PT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868254 TI - Agonistic and antagonistic activities of bacterially derived Rhodobacter sphaeroides lipid A: comparison with activities of synthetic material of the proposed structure and analogs. AB - Lipid A from the photosynthetic bacterium Rhodobacter sphaeroides (RSLA) has been previously shown to antagonize many of the effects of endotoxins from more pathogenic gram-negative bacteria. We have reported on the synthesis of the proposed structure of RSLA and determined that bacterially derived RSLA is not identical to its proposed structure (W.J. Christ, P. D. McGuinness, O. Asano, Y. Wang, M. A. Mullarkey, M. Perez, L. D. Hawkins, T. A. Blythe, G. R. Dubuc, and A. L. Robidoux, J. Am. Chem. Soc. 116:3637-3638, 1994). Here we report results of analyzing the antagonistic and agonistic activities of bacterially derived RSLA in comparison with the activities of chemically synthesized material of the proposed structure of RSLA and analogs. Results indicated that all compounds were approximately equally potent at inhibiting endotoxin-induced release of tumor necrosis factor alpha from human monocytes and human whole blood as well as endotoxin-induced generation of nitric oxide in murine macrophages. In addition, all compounds were of equivalent potencies at inhibiting the binding of 125I labelled lipopolysaccharide derivatized with 2-(p-azido-salicylamido) ethyl-1-3' dithiopropionate to murine macrophages. Higher concentrations of bacterially derived RSLA (10 to 100 microM) were agonistic in human and murine assays. In gamma interferon-treated murine macrophages, agonism was exhibited at concentrations as low as 100 nM. In contrast, all synthetic materials were either dramatically less agonistic or devoid of agonistic activity when tested at concentrations as high as 100 microM. It is possible either that bacterially derived RSLA contains a small amount of a highly agonistic impurity or that the agonistic activity of RSLA is intrinsic to its molecular structure. In either case, these biological results support our previous report concluding that biologically derived RSLA is not identical to synthetic material of its proposed structure. PMID- 7868255 TI - Relationships among capsular structure, phagocytosis, and mouse virulence in Klebsiella pneumoniae. AB - Klebsiella pneumoniae strains of the K2 capsular serotype are usually highly virulent in mice, which is in contrast to the low virulence of most other serotypes. Here we used a genetic approach to examine the relative contribution of capsule type to the virulence of K. pneumoniae in mice. We used wild-type strains expressing capsular polysaccharide (CPS) serotypes K2 (strain KPA1) and K21a (strains KPB1 and KPC1), which were then used to construct capsule-switched derivatives. The close proximity of the cps gene cluster to selectable his markers made it possible to mobilize the cps genes by conjugation from one serotype (donor) to another (recipient) and to obtain recombinants in which interserotype switching had occurred by reciprocal recombination. Each capsule switched derivative examined of the KPA and KPC strain backgrounds produced a CPS that was immunologically and structurally identical to that of the donor. Strain background was confirmed by demonstrating restriction fragment length polymorphism patterns identical to those of the respective recipients. The parent strains were then compared with capsule-switched recombinants for phenotypic properties associated with virulence. Clearance from the bloodstreams of mice was rapid in serotype K21a strains of either wild-type or recombinant origin, whereas K2 strains remained viable in the blood during the period examined. These differences appeared to be dependent upon the CPS type but independent of strain background. Binding to macrophages was higher in K21a strains than in those with the K2 capsule and was also independent of the strain background. Both blood clearance and macrophage-binding activities were completely inhibited by yeast mannan, suggesting that they were mediated via the macrophage mannose receptor. The K2 parent strain was highly virulent to mice (50% lethal dose [LD50], 3 x 10(3)), while the K21a parent strains demonstrated low virulence (LD50, > 2 x 10(8)). Interestingly, the virulence of recombinant KPC10(cpsK2), originally of the KPC1(cpsK21a) background, was intermediate (LD50, 4 x 10(5)). In contrast, both cpsK21a recombinants of the originally virulent KPA1 (cpsK2) background became nearly avirulent (LD50, > 2 x 10(8)). Six additional serotypes (K12, K24, K32, K55, K62, and K67) were examined, and all showed a positive correlation between the ability of the Klebsiella serotype to interact with a human mannose receptor, as expressed by Cos I cell recombinants, and the LD50 of the serotype. These results suggest that expression of a capsule which is recognized by the mannose receptor markedly affects the interaction with macrophages and blood clearance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7868256 TI - Induction of compartmentalized B-cell responses in human tonsils. AB - The capacity of tonsillar and nasal mucosal lymphoid tissues to serve as induction sites of local and/or distant B-cell responses in humans has been examined. The frequencies of vaccine-specific antibody-secreting cells (ASC) in cell suspensions from palatine tonsils (PT) and adenoids were determined after local (intra-tonsillar [i.t.]) and regional (intranasal [i.n.]) immunizations as well as peroral and parenteral immunizations with cholera and tetanus toxoids. While peroral and parenteral immunizations evoked negligible ASC responses in PT, i.t. vaccination induced a substantial ASC response which consisted of immunoglobulin G (IgG) and IgA ASC. Responses were highly restricted to immunized tonsils. Primary immunization in one PT followed by a second immunization of both PT evoked a larger ASC response in the primed tonsil. The latter ASC response was associated with higher frequencies of ASC precursors in primed tonsils. Furthermore, two i.n. immunizations induced only modest ASC responses in PT, although such immunizations evoked high ASC responses in adenoids. However, both i.t. and i.n. routes of immunization induced specific peripheral blood ASC responses, suggesting that a fraction of B cells activated in tonsils or in nasal mucosa may enter the circulation and disseminate to distant organs. These blood ASC responses preceded increases in both IgA and IgG antibody titers in nasal washes and serum samples. However, vaccine-specific ASC were not detected in duodenal cell suspensions from volunteers who had received i.t. or i.n. immunizations. Collectively, these results indicate that tonsils can serve as expression sites of locally induced antibody responses and support the development of immunological memory. Furthermore, tonsils may serve as powerful inductive sites for immune responses expressed in the upper aerodigestive tract. PMID- 7868257 TI - Lipopolysaccharide regulation of lipoprotein lipase expression in murine macrophages. AB - The enzyme lipoprotein lipase is expressed in a number of cell types and plays a central role in lipid metabolism. Multiple factors regulate its expression in a tissue-specific manner. In murine macrophages, lipopolysaccharide inhibits lipoprotein lipase enzyme activity. The current work examines this process in the established J774 macrophage line and primary peritoneal macrophages from endotoxin-sensitive (C3HeB/Fej) and endotoxin-resistant (C3H/Hej) murine strains. Lipopolysaccharide inhibition of macrophage lipoprotein lipase occurred at the enzyme and mRNA levels in a time- and concentration-dependent manner. Cells from endotoxin-resistant animals maintained their expression of lipoprotein lipase following treatment with lipopolysaccharide. Results of gel retention assays showed that lipopolysaccharide treatment of the J774 macrophages altered the level of nuclear proteins recognizing and binding the lipoprotein lipase promoter DNA. Nuclear extracts from resting J774 cells contained proteins which bound specifically to the octamer motif and to the CAAT box within the lipoprotein lipase promoter. Exposure of the J774 cells to lipopolysaccharide for 16 h increased the level of protein-octamer DNA complexes. Similar responses were obtained in endotoxin-sensitive, but not endotoxin-resistant, primary macrophages following in vitro treatment with lipopolysaccharide. This finding suggests that transcriptional events may contribute to the lipopolysaccharide regulation of macrophage lipoprotein lipase expression. PMID- 7868258 TI - Scavenger receptor pathway for lipopolysaccharide binding to Kupffer and endothelial liver cells in vitro. AB - We have investigated the interaction of Salmonella minnesota R595 lipopolysaccharide (ReLPS) depleted of Ca2+ and Mg2+ with both Kupffer and endothelial liver cells under serum-free conditions. Specific and saturable binding levels of 125I-ReLPS were similar in both types of cells with respect to divalent cation independence, susceptibility to proteases, and concanavalin A inhibition. By using partial structures of ReLPS, it was demonstrated that acidic 3-deoxy-D-manno-octulosonic acid residues and phosphoryl groups on lipid A are of primary importance in ReLPS binding. The role of ionic interactions in LPS recognition by the cells was further confirmed by susceptibility of the binding to competitive inhibition by polyanions. Both ReLPS and ReLPS partial structures inhibited the specific cellular binding of acetylated low-density lipoprotein (Ac LDL) by Kupffer cells and Ac-LDL- and formaldehyde-treated albumin by endothelial cells whose cellular accumulation is mediated by a different type(s) of scavenger receptor(s). In contrast, 125I-ReLPS binding to Kupffer and endothelial cells was not competed by Ac-LDL or formaldehyde-treated albumin. Our results indicate the scavenger pathway of LPS uptake by Kupffer and endothelial cells and the primary role of LPS anionic properties in this process. PMID- 7868259 TI - Evaluation of transferrin-binding protein 2 within the transferrin-binding protein complex as a potential antigen for future meningococcal vaccines. AB - Because the meningococcal transferrin receptor was shown to elicit bactericidal and protective antibodies in laboratory animals, we undertook a study of the protective role of each of the polypeptides within the Tbp1-Tbp2 complex. We developed a procedure to purify from Neisseria meningitidis B16B6 the two proteins in milligram amounts and raised specific antisera in rabbits and mice. Only antisera specific for Tbp2 displayed bactericidal activity against the parent strain. Mice immunized with purified Tbp2 survived a lethal challenge to a similar degree as animals immunized with the Tbp1-Tbp2 complex, demonstrating that Tbp2 played an important role in the protective activity observed with the complex. Both Tbp1- and Tbp2-specific antisera inhibited transferrin binding to the purified receptor in a solid-phase binding assay, suggesting that the antibodies were able to interact with the Tbp1 molecule only when it was removed from its membrane environment. Finally, Tbp2-specific immunoglobulins were able to lower the growth rate of the meningococci when human transferrin was their sole iron source. Therefore, in all four different systems tested, Tbp2 or antibodies specific for Tbp2 displayed biological characteristics close to those of the Tbp1-Tbp2 complex. This suggests that Tbp2 plays an important role in the protective activity of the complex, eliciting antibodies that are not only bactericidal but also inhibitory for meningococcal growth. PMID- 7868260 TI - Small repeating units within the Ureaplasma urealyticum MB antigen gene encode serovar specificity and are associated with antigen size variation. AB - Ureaplasma urealyticum is a common commensal of the female lower urogenital tract, yet it has been shown to be an important cause of chorioamnion infection, respiratory and central nervous system disease, and death in premature infants. It has been suggested that only certain serovars are capable of producing invasive disease. However, we previously showed that many serotypes are invasive and that perhaps antigen variability and host factors are more important determinants of ureaplasma infections than are different serotypes per se. The molecular characterization in this report describes a mechanism available to ureaplasmas for producing antigen variation. That antigen, designated MB and previously identified on U. urealyticum, contains serovar-specific and cross reactive epitopes, is produced both in vitro and in vivo, is a predominant antigen recognized during ureaplasma infections of humans, undergoes a high rate of size variation in vitro, and is size variable on invasive ureaplasma isolates. In the present study, we cloned and sequenced the gene of the MB antigen from serovar 3, the serovar most commonly isolated from humans. The 3' two-thirds of the gene was shown to contain identical 18-nucleotide tandem repeats. PCR analysis and direct sequencing of two variants indicated that alterations within this repeat region are responsible for the size variation of the MB antigen. Intact recombinant serovar 3 MB antigen and truncated products, expressed by coupled in vitro transcription and translation of the cloned gene, were immunoprecipitated by both a serovar-specific monoclonal antibody and the serum of a U. urealyticum-infected patient, and these results identified the repeat region of the MB antigen as serovar defining. Resolution of the precise amino acids responsible for specific epitopes and characterization of similar genes in the other serovars should yield reagents useful in elucidating the role of antigen size variants in disease production and the role of specific antibody in protection from ureaplasma disease. PMID- 7868261 TI - Adhesion of nontypeable Haemophilus influenzae from blood and sputum to human tracheobronchial mucins and lactoferrin. AB - Nontypeable Haemophilus influenzae strains are the most common pathogens encountered in patients with chronic bronchitis. These organisms chronically colonize the airways of patients and occasionally cause bacteremia. Nontypeable H. influenzae strains have been demonstrated microscopically to bind to mucus, but quantitative studies of adhesion have not been published to date. We have therefore developed a reproducible microtiter plate assay to study mucin binding and have examined the adhesion of sputum and blood strains of nontypeable H. influenzae. The assay is similar to that described for Pseudomonas aeruginosa (S. Vishwanath and R. Ramphal, Infect. Immun. 45:197-202, 1984), but notably 2% Tween 20 is used to desorb bacteria from the wells to quantitate bacterial binding. Using a standard strain, we have established that 1 h of incubation is optimum with an inoculum of < or = 5 x 10(8) CFU/ml. The standard strain binds to bronchitic and cystic fibrosis mucins equally well but binds less to bronchiectasis mucins. It does not bind to bovine serum albumin or fetuin. We have also examined the levels of adhesion of freshly isolated sputum and bacteremia strains and find very significant differences in adhesion. Blood strains bound six to seven times less than sputum strains ([13.8 +/- 7] x 10(2) per well versus [102 +/- 43] x 10(2); P < 0.001). Studies with adhesion to lactoferrin, another glycosylated protein, revealed variable binding of respiratory strains but marked binding of blood strains compared with mucin. An isogenic pair of respiratory and blood isolates was examined by electron microscopy but did not show surface differences. We speculate that bacteremic strains studied may have masked, lost, or downregulated adhesin production to allow them to escape from mucins or upregulated adhesins for lactoferrin to invade the bloodstream. PMID- 7868262 TI - A porin from Klebsiella pneumoniae: sequence homology, three-dimensional model, and complement binding. AB - A recombinant plasmid containing ompK36, the gene coding for the Klebsiella pneumoniae outer membrane protein OmpK36, was constructed by transposon mutagenesis and subcloning. Clones were identified in a cosmid library in Escherichia coli on the basis of their reaction with antiserum against the OmpK36 protein and by the presence in gel electrophoretic analysis of a band in E. coli outer membranes migrating with a mobility corresponding to 36 kDa. The ompK36 encoded protein exhibited characteristic properties of porins, such as heat modifiability and resistance to trypsin. The sequence of the gene revealed that OmpK36 is a close relative of the enterobacterial porin family, with a high degree of homology with E. coli OmpC, PhoE, and OmpF. On the basis of the structures of OmpF and PhoE porins, determined previously by X-ray analysis, it appears likely that the three-dimensional structure of OmpK36 also contains the motif of a 16-stranded beta-barrel, with long loops on one end and short turns on the other. Like the OmpC porin from E. coli, OmpK36 contains a long insertion in loop 4. The results of a binding study of complement component C1q to OmpK36 and the analysis of the OmpK36 model suggest that C1q binding sites are covered by the lipopolysaccharide core in the native porin. PMID- 7868263 TI - Neutrophil alkaline phosphatase activity increase in bacterial infections is not associated with a general increase in secretory vesicle membrane components. AB - The content of alkaline phosphatase (ALP) was determined in neutrophils isolated from patients with acute bacterial infections by a standard enzyme assay. Compared with control cells, patient cells exhibited about a fivefold increase in ALP activity. There was no difference between the ALP Km values of control and patient cells, which indicates that the elevated activity in patient cells was due to the presence of increased amounts of the enzyme. The ALP isozyme in both cell types was determined to be the tissue-unspecific ALP. The fact that much of the ALP activity was measurable only in the presence of detergent suggested that the enzyme was localized in the secretory vesicles, a putative reservoir of plasma membrane components. The amount and subcellular distribution of two other secretory vesicle membrane proteins, i.e., cytochrome b and complement receptor 3, were not altered; hence, we conclude that there was no general increase in amounts of secretory vesicle membrane constituents in the patient cells. PMID- 7868264 TI - Molecular cloning of a 30-kilodalton lysine-rich surface antigen from a nonpathogenic Entamoeba histolytica strain and its expression in a pathogenic strain. AB - A monoclonal antibody (MAb), 318-28, that specifically reacts with a 30-kDa antigen present on membrane surfaces of all nonpathogenic (NP) Entamoeba histolytica strains tested and which did not react with pathogenic (P) strains was used for the isolation of the cDNA coding for this antigen from an expression library of an NP E. histolytica strain. The deduced amino acid composition was rich in lysine residues (14.5%), with some sequence similarity to a polyadenylate binding protein. Southern and Northern (RNA) blot analyses, as well as amplifications of DNA segments by PCR, indicate that a very similar gene (identity of 96.5%) exists in P strains of E. histolytica. Unexpectedly, the NP specific antigen was also identified by MAb 318-28 on the surfaces of a cloned, xenically cultivated and well-characterized P strain (BNI:0591) that was recently isolated from a human liver abscess. Binding of the MAb, both to the cell surfaces and to Western blots (immunoblots), was abolished, however, upon axenization of the BNI:0591 cultures. Oligonucleotide primers, designed to anneal only to specific DNA sequences of the NP 30-kDa protein gene copy, amplified a DNA segment from P strain BNI:0591 which was identical in sequence to that of the NP 30-kDa protein gene. Our findings indicate that a P strain of E. histolytica can possess and express, under certain growth conditions, an antigen that is usually detected only in NP strains. PMID- 7868265 TI - Hepatocytes can serve as accessory cells in the response of immune T lymphocytes to heat-killed Listeria monocytogenes. AB - Previous findings in our laboratory indicated that the bulk of Listeria monocytogenes injected intravenously into mice and recovered in the liver is taken up and replicates within hepatocytes. Other investigators have shown that hepatocytes can display costimulatory adhesion molecules, express major histocompatibility complex class I and II molecules, and secrete a number of cytokines, including interleukin-1 (IL-1), IL-6, and IL-8. These data suggest that hepatocytes may serve as accessory cells in the immune response to L. monocytogenes. The accessory function and capacity of hepatocytes to present listerial antigens, however, have never been explored. We undertook a series of experiments to examine the response of Listeria-immune T lymphocytes to murine hepatocytes preincubated with heat-killed listeriae (HKL). Electron micrographs showing the organism within membrane-limiting vacuoles demonstrated the capacity of hepatocytes to internalize HKL. T cells cocultured with hepatocytes pulsed with HKL exhibited a 5- to 10-fold increase in [methyl-3H]thymidine incorporation relative to T cells cultured with either hepatocytes or HKL alone. Similarly, gamma interferon production by immune T cells was elevated significantly in cultures that contained both hepatocytes and HKL. The optimal response of T cells required lysosomal processing of HKL by hepatocytes and contact between the two cell populations. Furthermore, maximum T-cell proliferation and gamma interferon production were dependent upon the presence of CD4+ T lymphocytes and the expression of Ia antigens. Taken together, these findings demonstrate that hepatocytes pulsed with HKL can stimulate the antigen-specific response of immune T lymphocytes. These results suggest that hepatocytes can serve as accessory cells in host defenses to listerial infections of the liver. PMID- 7868266 TI - Impact of microfilaremia on maintenance of a hyporesponsive cellular immune response in Brugia-infected gerbils (Meriones unguiculatus). AB - The purpose of these experiments was to define the significance of the microfilarial stage to the hyporesponsive condition seen in lymphatic filariasis. Two types of experiments were conducted with Brugia pahangi-infected gerbils. In one, in vitro lymphocyte blastogenesis and in vivo granuloma formation in response to parasite antigen were correlated to microfilaremia in chronically infected individuals. In a second set of experiments, the level of in vivo granuloma formation was assessed following chemotherapeutic removal of microfilariae with ivermectin. The results indicated that the microfilarial stage alone is not responsible for the maintenance of the low cellular responses seen during chronic infections in this model. Furthermore, the data suggest that the degree of downregulation of these responses may be related to parasite burden. PMID- 7868267 TI - Kinetics of chlamydial antigen processing and presentation to T cells by paraformaldehyde-fixed murine bone marrow-derived macrophages. AB - Macrophages are potential candidates for antigen presentation to chlamydial specific CD4+ T cells. We have studied the kinetics of chlamydial antigen processing and presentation by using paraformaldehyde-fixed bone marrow-derived macrophages (BMDM) and splenic T cells isolated from chlamydia-infected mice. BMDM were inoculated with different multiplicities of heat-killed chlamydial elementary bodies, and at different times postingestion, the macrophages were fixed with paraformaldehyde and used as antigen-presenting cells in T-cell proliferation assays. T-cell proliferative responses were shown to be dependent on the chlamydial inoculum size, with a multiplicity of 10 chlamydiae per macrophage producing optimum T-cell proliferation. Temporal experiments showed that peak T-cell proliferative responses occurred between 4 and 12 h postingestion of chlamydiae by BMDM. T cells proliferated strongly to antigen when presented by H-2-matched BMDM but not when presented by H-2-disparate BMDM, demonstrating that T-cell recognition of processed chlamydial antigen was major histocompatibility complex restricted. BMDM inoculated with 10 chlamydiae per cell and fixed at 8 h postinoculation were shown to be as stimulatory to T cells as conventional splenic antigen-presenting cells. Because large numbers of BMDM can be propagated in vitro, and experimental conditions that provide optimum presentation of processed chlamydial antigen to chlamydia-specific CD4+ T cells can be defined, BMDM may be a potentially useful source for the isolation of naturally processed parasite antigen from major histocompatibility complex class II molecules. PMID- 7868268 TI - Molecular and immunological characterization of the highly conserved antigen 84 from Mycobacterium tuberculosis and Mycobacterium leprae. AB - Crossed immunoelectrophoresis (CIE) has been used to develop a reference system for classifying mycobacterial antigens. The subsequent use of specific antibodies allowed further determination of antigens by molecular weight. The monoclonal antibody F126-2, originally raised against a 34-kDa antigen of Mycobacterium kansasii, reacted with antigen 84 (Ag84) in the CIE reference system for Mycobacterium bovis BCG and Mycobacterium tuberculosis. To characterize Ag84, we screened a lambda gt11 gene library from M. tuberculosis with antibody F126-2 and identified the encoding gene. The corresponding Mycobacterium leprae Ag84 gene was subsequently selected from a cosmid library, using the M. tuberculosis gene as a probe. Both genes were expressed as 34-kDa proteins in Escherichia coli, and the recombinant proteins indeed corresponded to Ag84 in the CIE reference system. The derived amino acid sequences of the M. tuberculosis and M. leprae proteins showed 85% identity, which indicates that Ag84 constitutes a group of highly conserved mycobacterial antigens. Antibodies of almost 60% of lepromatous leprosy patients responded to Ag84, indicating that the protein is highly immunogenic following infection in multibacillary leprosy. PMID- 7868269 TI - Differential activation of Brucella-reactive CD4+ T cells by Brucella infection or immunization with antigenic extracts. AB - In order to induce acquired cellular resistance to facultative bacterial pathogens, infection with live organisms is required. We have previously demonstrated that spleen cells from Brucella-infected mice produced gamma interferon (IFN-gamma) and interleukin-2 (IL-2) in response to Brucella antigens in vitro, while spleen cells from mice immunized with soluble Brucella proteins (SBP) produced substantial amounts of IL-2 but no detectable amount of IFN-gamma. In this study, we further analyzed the response of T cells from Brucella-infected mice and SBP-immunized mice and demonstrated that CD4(+)-enriched cells from SBP immunized mice also produced significant amounts of IL-4, which was not detected in bulk cultures of spleen cells from infected mice. Limiting dilution analysis showed that infection resulted in a higher precursor frequency of IFN-gamma producing CD4+ T cells and a lower precursor frequency of IL-4-producing CD4+ T cells, while immunization with SBP resulted in a higher precursor frequency of IL 4-producing cells and a very low frequency of IFN-gamma-producing cells. The precursor frequencies of IL-2-producing cells for the two groups were similar. Furthermore, IFN-gamma-producing CD4+ T cells from infected donor mice were capable of mediating resistance against challenge infection in recipient mice, but IL-4-producing CD4+ T cells from immunized mice failed to do so. These results indicate that the form of antigen has a profound influence on the outcome of the immune response. The results are discussed in light of the supposed dichotomy between Th1 and Th2 cytokine responses. PMID- 7868270 TI - Penetration and damage of endothelial cells by Candida albicans. AB - The mechanisms of phagocytosis of Candida albicans by human vascular endothelial cells and subsequent endothelial cell injury were examined in vitro. Both live and killed C. albicans cells were phagocytized by endothelial cells. This organism specifically induced endothelial cell phagocytosis because neither Candida tropicalis nor Torulopsis glabrata was ingested. Endothelial cell microfilaments polymerized around C. albicans as the organisms were phagocytized. Cytochalasin D inhibited this polymerization of microfilaments around C. albicans and blocked phagocytosis. The blocking of actin depolymerization with phalloidin had no effect on microfilament condensation around the organism, indicating that the microfilaments surrounding C. albicans are formed from a pool of G-actin. Intact microtubules were also necessary for the phagocytosis of C. albicans, since the depolymerizing of endothelial cell microtubules with nocodazole prevented the condensation of actin filaments around the organisms and inhibited phagocytosis. In contrast, microtubule depolymerization was not required for microfilament function because the blocking of microtubule depolymerization with taxol had no effect on microfilament condensation around C. albicans. The phagocytosis of C. albicans was pivotal in the induction of endothelial cell damage, since the blocking of candidal internalization significantly reduced endothelial cell injury. Endothelial cells were not damaged by phagocytosis of dead organisms, indicating that injury was caused by a factor associated with viable organisms. Therefore, C. albicans is uniquely able to induce endothelial cell phagocytosis by comparison with non-albicans species of Candida. Furthermore, at least two components of the endothelial cytoskeleton, microfilaments and microtubules, are necessary for the phagocytosis of C. albicans. PMID- 7868271 TI - Degradation of humoral host defense by Candida albicans proteinase. AB - The effect of an extracellular proteinase from the pathogenic yeast Candida albicans on the bactericidal and opsonizing activities of human serum was studied. The ability of human polymorphonuclear leukocytes to kill Staphylococcus aureus was greatly reduced when the bacteria were opsonized with human serum treated with the proteinase. The reduction in the opsonizing activity of human serum was attributed to degradation of the Fc portion of immunoglobulin G by the action of C. albicans proteinase as determined by immunoprecipitation reaction. However, the Fab portion of immunoglobulin G was resistant to proteolysis by the proteinase. A clear reduction in the bactericidal activity of human serum against Escherichia coli was observed when the serum was treated with C. albicans proteinase. The reduction of serum bactericidal activity was attributed to the degradation of complement C3 by proteolysis by the proteinase as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, while C5 resisted the action of the proteinase. As determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the proteinase also degrades endogenous proteinase inhibitors, such as alpha 2 macroglobulin and alpha 1 proteinase inhibitor, which are involved in regulating inflammation. These results suggest that destruction of a host's defense-oriented or regulatory proteins facilitates debilitation of the infected host. PMID- 7868272 TI - Pasteurella multocida produces a protein with homology to the P6 outer membrane protein of Haemophilus influenzae. AB - An antibody specific for a 16-kDa outer membrane protein of a rabbit strain of Pasteurella multocida was used to probe representatives of all 16 somatic serotypes of P. multocida, as well as the vaccine strains CU and M9, and all were shown to express the protein. The gene encoding this protein was cloned and sequenced and found to have extensive sequence homology with the gene encoding the P6 protein of Haemophilus influenzae. The protein in P. multocida has been designated P6-like. The gene encoding the P6-like protein was used to probe members of the family Pasteurellaceae and other gram-negative bacteria. Representatives of all 16 somatic serotypes (as well as the vaccine strains CU and M9) of P. multocida hybridized with the P6-like gene under conditions of high stringency. The DNA from H. influenzae hybridized weakly with the P6-like gene under these conditions, but Pasteurella haemolytica (representatives of A and T biotypes), Bordetella bronchiseptica, B. avium, Actinobacillus suis, A. suis like, A. lignieresii, A. ureae, A. rossii, A. pleuropneumoniae, A. equuli, and various members of the family Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, and Salmonella typhimurium) did not hybridize detectably. Under conditions of lower stringency, the P6-like gene also hybridized strongly with DNA from P. multocida, H. influenzae, and A. rossii but weakly with DNA from P. haemolytica and members of the genus Actinobacillus. These results suggest that the P6-like protein of P. multocida might be useful as an immunizing product to protect poultry from avian cholera. This suggestion stems from (i) our finding that the P6-like protein in P. multocida is widely distributed among all the somatic serotypes and (ii) the previous work of others demonstrating that the P6 protein of H. influenzae elicits a protective immune response in animal models of human disease. PMID- 7868274 TI - From 'Our Town' to 'Ghost Town'?: the changing context of home for rural elders. AB - This research, grounded in a contextual view of environmental stress, employed an experiential field approach to explore outcomes of the continuing rural crisis of the past decade for elderly residents of four small Kansas towns. These rural changes threaten the survival of many towns, and affect their elderly residents, who often have enduring economic, social, and psychological investments in their homes and communities. At the same time, changes associated with aging may lead to transitions in the experience of home and community for these elderly individuals, regardless of the town's health. The two sources of change may have multi-faceted impacts on the well-being of the elderly individuals who experience them. Aspects of the research described here focus on environmental stressors related to housing and the meaning of attachment to home within economically threatened communities. Some findings presented support previous research, while others reflect the region's unique socio-historical environment as a part of the Western Frontier. Implications for policy alternatives and the well-being of rural elderly are discussed. PMID- 7868275 TI - Nostalgic memories in dementia--a case study. AB - The literature indicates that some moderately to severely demented elderly people can still recall their emotionally subjective past. Emotion and cognition have a relationship that can be clearly seen in the recall of nostalgic memories. This article outlines a case study that illustrates how emotional autobiographical memories of past events can be stimulated through the individual use of reminiscence and counseling skills. The authors suggest that there are possible therapeutic effects attached to this approach and that this is an area worthy of further investigation. PMID- 7868273 TI - Genetic diversity and relationships among Streptococcus pyogenes strains expressing serotype M1 protein: recent intercontinental spread of a subclone causing episodes of invasive disease. AB - Chromosomal diversity and relationships among 126 Streptococcus pyogenes strains expressing M1 protein from 13 countries on five continents were analyzed by multilocus enzyme electrophoresis and restriction fragment profiling by pulsed field gel electrophoresis. All isolates were studied for the presence of the gene encoding streptococcal pyrogenic exotoxin A by PCR. Strain subsets were also examined by automated DNA sequencing for allelic polymorphism in genes encoding M protein (emm), streptococcal pyrogenic exotoxin A (speA), streptokinase (ska), pyrogenic exotoxin B (interleukin-1 beta convertase) (speB), and C5a peptidase (scp). Seven distinct emm1 alleles that encode M proteins differing at one or more amino acids in the N-terminal variable region were identified. Although substantial levels of genetic diversity exist among M1-expressing organisms, most invasive disease episodes are caused by two subclones marked by distinctive multilocus enzyme electrophoretic profiles and pulsed-field gel electrophoresis restriction fragment length polymorphism (RFLP) types. One of these subclones (ET 1/RFLP pattern 1a) has the speA gene and was recovered worldwide. Identity of speA, emm1, speB, and ska alleles in virtually all isolates of ET 1/RFLP type 1a means that these organisms share a common ancestor and that global dispersion of this M1-expressing subclone has occurred very recently. The occurrence of the same emm and ska alleles in strains that are well differentiated in overall chromosomal character demonstrates that horizontal transfer and recombination play a fundamental role in diversifying natural populations of S. pyogenes. PMID- 7868276 TI - Subjective well-being measures: reliability and validity among Spanish elders. AB - The Philadelphia Geriatric Center Morale Scale, Life Satisfaction Index, and Affect Balance Scale were translated into Castilian Spanish and Catalan. Responses to these scales were obtained by interviews with 151 elderly persons living in Spain. Reliability estimates for the Life Satisfaction Index and the Affect Balance subscales were comparable to those for English-speaking samples, while reliability estimates for the Philadelphia Geriatric Center Morale Scale were somewhat lower. Validity estimates among these scales were consistent with previous research and previously reported factor structures were found to fit the present data reasonably well, although factor loadings were lower than those previously reported. English and translated versions of the scales are provided in Appendix A. PMID- 7868277 TI - Six ages of man as determined by athletic performance. AB - It is submitted that a useful quantitative measure of aging is provided by measures of athletic performance. Whereas there are enormous differences in the athletic ability of individuals, any individual's performance may be related to the top performance by means of a ratio. This article describes the development of a model for the top performance and hence a model for the performance of any person at any age. Previous work has concentrated on the effect of aging on oxygen consumption. Because of the close relationship between oxygen consumption and athletic performance, compatibility with previous research is assured. The model shows that athletic performance undergoes significant changes at certain ages and that these change points break the aging process into six "ages of man." The model is however far from complete and needs to be based on more representative data. It is hoped that publication of the model will result in further studies in this field. PMID- 7868278 TI - The need for qualitative research on mental health of elder Hispanics. AB - This article contends that purely quantitative measures of Hispanic aged mental health have been insufficiently sensitive to cultural factors. It describes the uses and limitations of qualitative methods, especially in-depth interviews and life histories, and suggests that researchers should include the use of psychometric tests in these interviews, in order to improve the interpretations of the data. In this article the Adlerian perspective is developed along with several relevant dimensions for evaluating cases. Finally, seven cases illustrating the diversity of Hispanic elders are presented. PMID- 7868279 TI - Levoatriocardinal vein in mitral atresia mimicking obstructive total anomalous pulmonary venous connection. AB - This report briefly describes two cases of levoatriocardinal vein, in the setting of mitral atresia and a restrictive interatrial shunt, with clinical as well as echocardiographic features mimicking obstructive total anomalous pulmonary venous connection. One patient died of pulmonary hypertensive crisis, and the other survived the palliative procedures including the atrioseptectomy and pulmonary artery banding. The echocardiography, cine-angiocardiography, and magnetic resonance image for such an anomalous channel are presented. It is tempting to speculate that the thrombocytopenia and indirect hyperbilirubinemia be associated with the destructive consumption of thrombocytes and red blood cells in the serpentine levoatriocardinal vein. PMID- 7868280 TI - Does thrombolysis affect the prognostic value of the post-infarct exercise test? AB - There has been some debate on usefulness of the exercise test in risk stratification after myocardial infarction in the thrombolytic era. This was assessed in 295 patients of whom 184 were treated with thrombolysis. Each had an exercise test using a modified Naughton protocol within 14 days of acute myocardial infarction. The tests were graded as high risk positive (112), low risk positive (83), or negative (100). These gradings predicted use of multiple drug therapy (p = 0.05), severity of coronary artery disease (p < 0.01), and coronary artery bypass grafting (p < 0.01). There was no influence on heart failure, recurrent myocardial infarction or death. This was independent of the use of thrombolytic therapy. The whole group had a good prognosis with a mortality of 2.4% after 56 weeks' follow-up. The exercise test is still a useful screening test after myocardial infarction. In this study, there was a high negative predictive accuracy of 91% for any event. Its use is not altered by thrombolysis. The finding of a lack of influence of the exercise test on major events may be a reflection of the current good prognosis after myocardial infarction and the prompt use of revascularisation. PMID- 7868281 TI - Reduced cardiac extraction of norepinephrine and epinephrine in patients with heart failure--correlation with left ventricular function. AB - To assess whether the impairment of neuronal norepinephrine (NE) uptake is involved in the increased NE release observed in the failing heart, we examined the cardiac extractions of NE and epinephrine (E) and their correlation with left ventricular function in 16 patients with anterior transmural old myocardial infarction (OMI) and 18 patients with dilated cardiomyopathy (DCM). The plasma NE and E levels were both increased in OMI and DCM, particularly in the coronary sinus, as compared with those in 16 control subjects (Control). The cardiac NE and E extractions were significantly reduced in OMI (P < 0.001) and in DCM (P < 0.001) as compared with those in the Control (NE: -38 +/- 36% in OMI, -33 +/- 28% in DCM, and 14 +/- 18% in Control; E: 30 +/- 12% in OMI, 32 +/- 17% in DCM, and 54 +/- 8% in Control). However, there was no reduction in the NE and E extraction in the leg in OMI and DCM. Cardiac NE and E extractions both showed significant correlation with the left ventricular ejection fraction (r = 0.685, P < 0.001 and r = 0.609, P < 0.001, respectively). We conclude that, in patients with heart failure, NE release from the heart is increased partially due to the reduction of the cardiac neuronal uptake of NE which is proportional to the severity of left ventricular dysfunction. PMID- 7868282 TI - Thyrotoxicosis, rheumatic heart disease and fever. PMID- 7868283 TI - Lack of correlation between coronary risk factors and CAD severity. AB - The coronary arterial lesions seen by angiography in 1666 consecutive male patients were converted to a score by the standardized scoring system advocated by Gensini. The resulting score, which allowed the disease to be expressed as a continuous variable, was effectively utilized to see the correlations between the severity of coronary arterial disease (CAD) and individual risk factors/risk markers. Significant correlations were seen between severity and age (P < 0.001), with a very low coefficient of correlation of 0.0873. On univariate analysis, no correlation was found between CAD severity and diabetes, smoking, positive family history of CAD, hypertension and other lipid fractions. On multiple regression analysis, significant correlations were found between severity and LDL Cholesterol, family history and total cholesterol after adjusting for other factors. The R2 for all these risk factors was only 14.1%. It is concluded that, although strong associations exist between risk factors and the occurrence of CAD, the small quantitative association detected between the presence of risk factors and the severity of disease is weak. PMID- 7868284 TI - A comparative study of risk factors for acute myocardial infarction amongst men of Indo-origin in Trinidad and the UK. AB - A high cardiovascular mortality rate exists amongst people of Indo-origin in Trinidad (third generation migrants) and the United Kingdom (first generation migrants). To investigate the differences in cardiovascular risk factors in these two populations, we surveyed all male patients of Indo-origin with acute myocardial infarction, admitted over a similar 8-week period to the Coronary Care Units of a district general hospital in Birmingham, United Kingdom and a similar hospital in San Fernando, Trinidad. Nineteen patients (mean age 62.2 years +/- S.D. 2.58) were admitted to the Birmingham hospital (UK Group) and fifty-five (mean age 58.1 years +/- S.D. 1.44) to the San Fernando hospital (Trinidad Group). There was no age difference between the groups (P = 0.18). There was a significantly greater proportion of smokers in the Trinidad group (70.9% vs. 63.2%, chi 2 = 4.56, P = 0.03), which also had a higher proportion of diabetics (36.4% vs. 31.6%) and hypertensives (34.5% vs. 31.6%). Mean systolic and diastolic blood pressures were higher in hypertensives from the Trinidad group (Trinidad group 146.6 mmHg +/- 16.9/93.4 mmHg +/- 11.4 vs. UK group 120.8 mmHg +/ 25.4/75.0 mmHg +/- 13.4; P < 0.05). The mean waist to hip ratio was greater in the Trinidad group (1.01 +/- S.D. 0.06) when compared to the UK group (0.95 +/- S.D. 0.05) (paired t-test, P < 0.01). Only six Trinidadian males performed regular exercise and only four of the UK group did so.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868285 TI - Plasma renin activity in chagasic patients with and without congestive heart failure. AB - Chagasic patients with advanced heart disease have fluid retention-dependent symptoms. Since fluid retention is mostly dependent on the renin-angiotensin aldosterone system, chagasic patients with congestion related symptoms should have activation of the renin-angiotensin-aldosterone system. The purpose of this investigation was to determine the plasma renin activity baseline values of chagasic patients with and without congestive heart failure. Twenty-eight patients with positive serology for Chagas' disease were studied. Nineteen patients were asymptomatic (functional class I New York Heart Association) and nine were symptomatic (functional classes II-IV). Cardiac catheterization and ventricular cineangiography were performed on 20 patients. The symptomatic patients had significantly higher plasma renin activity levels (4.11 +/- 1.03 ng/ml/h) than the asymptomatic patients (1.08 +/- 0.11 ng/ml/h, P < 0.001) and the normal sedentary controls (1.65 +/- 0.22 ng/ml/h, P < 0.05, mean +/- S.E.). The plasma renin activity baseline values of the asymptomatic and symptomatic patients correlated directly with the baseline heart rate (r = 0.77, P < 0.0001). The symptomatic patients had larger ventricular volumes, moderately depressed ejection fractions and increased left ventricular end-diastolic pressures. The plasma renin activity baseline values also correlated directly with the left ventricular diastolic pressures (r = 0.70, P < 0.0006) and with the left ventricular diastolic (r = 0.66, P < 0.001) and systolic volumes (r = 0.67, P < 0.001). These results indicate that chagasic patients with fluid retention dependent symptoms and hemodynamic evidence of left ventricular systolic dysfunction have activation of the renin-angiotensin-aldosterone system. PMID- 7868286 TI - Effect of 24-h blood pressure levels and circadian blood pressure rhythm on left ventricular structure and function in isolated systolic hypertension. AB - Forty-one participants (mean age 69 +/- 5.6 years) were examined by fully automatic blood pressure monitor and Doppler echocardiography to gain information on the ambulatory blood pressure and the left ventricular structure and function in isolated systolic hypertension. Cumulative sum (cusum)-derived statistics was used to quantify circadian blood pressure rhythm and 24-h blood pressure levels were defined as mean blood pressure values during 24 h, waking (06:00-22:00 h) and sleeping (22:00-06:00 h) periods, respectively. Most of the derivatives of ambulatory blood pressure, including cusum-derived statistics and 24-h blood pressure levels, were significantly related with the left ventricular structural (left ventricular posterior wall and interventricular septum thickness) and functional (acceleration time in the left ventricular outflow tract and early diastolic deceleration time) indexes. Among the left ventricular structural and functional indexes, interventricular septum thickness at end diastole had the strongest correlation with sleeping diastolic mean blood pressure (r = 0.41, P < 0.01), left ventricular posterior wall at end diastole, the best with 24-h systolic mean blood pressure (r = 0.41, P < 0.01), acceleration time the strongest with systolic cusum-derived circadian alteration magnitude (r = 0.49, P < 0.01) and early diastolic deceleration time the greatest with diastolic cusum derived trough blood pressure (r = 0.45, P < 0.01). We conclude that left ventricular structural changes rely on 24-h systolic and diastolic blood pressure levels, whereas left ventricular functional variations may be more dependent upon circadian blood pressure rhythm in elderly patients with isolated systolic hypertension. PMID- 7868287 TI - Echocardiographic evidence of persistent pericardial effusion after open heart surgery. AB - Cross-sectional and M-mode echocardiography were used to review 33 patients 6-28 months (mean 19 months) after open heart surgery. Eleven patients had had echocardiographic signs of pericardial effusion during the first week after open heart surgery (Group A), and 22 had not (Group B). At review, pericardial effusion was found in 73% of subjects in Group A compared with 18% of those in Group B (P < 0.01). On average, posterior effusions were small (mean dimension in systole 0.9 cm) but they were detected reproducibly (interobserver agreement 97%). Anterior echo-free spaces (< 0.5 cm) were found frequently, but interobserver variation in their detection was high (agreement in 68%). Symptoms did not correlate with the presence of a late post-operative effusion but the groups were not matched for rhythm or ventricular function. Five patients in Group A had developed atrial fibrillation in association with their early post operative effusion, and four of these had persisting atrial fibrillation at this review. These results suggest that echo-free spaces around the heart, suggestive of small pericardial effusions, may persist for many months after open heart surgery. PMID- 7868288 TI - Detection of microinfarction in patients with unstable angina: study by 111In antimyosin imaging. AB - To examine the incidence of a positive indium-111 antimyosin scintigraphy in patients with unstable angina, we prospectively examined 25 patients with unstable angina and 11 patients with stable angina. All patients were injected with 2 mCi of indium-111 on admission and planar scintigraphy was performed 48 h later. Symptoms and signs of ischemia indicating severity of ischemia were monitored during the period between injection and scanning. None of the patients developed a rise in cardiac enzymes suggesting myocardial necrosis. Seven (28%) of the 25 patients with unstable angina had positive antimyosin scanning; no stable patients had positive scanning. All seven patients with unstable angina and positive scanning had signs of severe ischemia (four patients had multiple episodes of > 2/day, three patients had prolonged episodes of > 15 min, three patients had ST depression in > 3 EKG leads) while only one of the eighteen unstable patients with negative scannings had signs of severe ischemia (P < 0.001). In conclusion, (1) a significant number of unstable angina patients present positive antimyosin scanning without an elevation of cardiac enzymes and (2) these patients usually present multiple or severe episodes of ischemia indicating that during these episodes, minor myocardial necrosis, undetected by enzymes, may occur. PMID- 7868289 TI - Recurrent, biatrial, familial cardiac myxomas. AB - A case of familial, recurrent, biatrial cardiac myxoma is reported. Histiological examination of a recurrent myxoma revealed prominent glandular differentiation. PMID- 7868290 TI - Doppler imaging of an inadvertent anastomosis of modified Blalock-Taussig shunt to the right upper pulmonary vein. AB - In a newborn infant with a complex congenital heart disease, a right modified Blalock-Taussig anastomosis was created because of the pulmonary atresia. A 4-mm Gore-Tex tube was inadvertently connected to the upper right pulmonary vein. Clinical signs of an arteriovenous fistula with no improvement in oxygen saturation were noticed immediately after surgery. This complication was confirmed by colour Doppler examination and angiography. Reanastomosis of the tube to the right pulmonary artery was then performed. PMID- 7868291 TI - Sub-mitral aneurysm with aortoarteritis: case report of an unusual association. PMID- 7868292 TI - Infracardiac total anomalous pulmonary venous connection in tetralogy of Fallot with decreased pulmonary flow and masked pulmonary venous obstruction: report of one case. AB - We describe an 8-month-old male infant, who received a rerouting procedure for infracardiac total anomalous pulmonary venous connection and a 4-mm Gore-Tex central shunt for tetralogy of Fallot with pulmonary atresia. The masking effect of the pulmonary outflow in tetralogy of Fallot on the pulmonary venous obstruction in infracardiac total anomalous pulmonary venous connection is discussed. Preoperative recognition of this rare association is warranted, as palliative surgery alone may be disastrous. In addition, juxtaductal pulmonary artery coarctation in tetralogy of Fallot with pulmonary atresia may play a role in camouflaging the pulmonary venous obstruction in this case. Unmasking pulmonary venous obstruction by oral prostaglandin and augmenting pulmonary blood flow by a Gore-Tex shunt, pari passu, did harm this patient. PMID- 7868293 TI - Antitumor effect of DT-5461a, a synthetic low-toxicity lipid A analog, involves endogenous tumor necrosis factor induction subsequent to macrophage activation. AB - We previously showed that the synthetic lipid A derivative DT-5461a exhibited significant antitumor effects against various murine solid tumors, probably via activation of host immune systems. To clarify the participation of the macrophage stimulating effect of DT-5461a in the antitumor mechanisms, we studied the ability of this compound to induce cytostatic macrophages and TNF production in murine systems. Cytostatic macrophages were induced by treatment with DT-5461a either in vitro or in vivo. DT-5461a also induced TNF production by resident peritoneal macrophages or spleen cells obtained from untreated mice. When spleen cells prepared from DT-5461a-treated mice were re-stimulated in vitro with DT 5461a, no TNF was produced by cells obtained at 1 day after the treatment. This may be due to transient refractoriness of macrophages to the compound, since the response to re-stimulation with DT-5461a recovered in cells obtained at 3 or 5 days after treatment. Moreover, while the serum TNF production and antitumor effects by DT-5461a decreased on daily administration, they were elicited by intermittent administration at intervals of 3 days or more. This suggests that the antitumor effects of DT-5461a depend on the TNF-producing activity of macrophages. These results indicate that DT-5461a possesses significant macrophage-stimulating activity, and that macrophages so activated mediate the DT 5461a-induced augmentation of host response against solid tumors. PMID- 7868294 TI - Triptolide suppresses T-lymphocyte proliferation by inhibiting interleukin-2 receptor expression, but spares interleukin-2 production and mRNA expression. AB - The purpose of this study was to elucidate the mechanism of action of triptolide on the T-lymphocyte-mediated immune response. Lymphocytes were incubated with a suboptimal dose of Con A or PHA in the presence or absence of varying doses of triptolide to assess the effect of triptolide on lymphocyte proliferation, interleukin-2 (IL-2) production and IL-2 receptor expression. Then, Con A or PHA induced T-blast cells were cultured with a sufficient dose of recombinant human IL-2 in the presence or absence of triptolide to evaluate the effect of triptolide on the interaction of IL-2 and IL-2 receptors. The effect of triptolide on the immune response in vivo was also investigated. The results of these studies clearly demonstrated that triptolide selectively inhibited the T lymphocyte proliferative response to Con A and PHA, but had less effect on LPS induced B-lymphocyte proliferation. Triptolide also suppressed the expression of IL-2 receptors on PHA induced T-blast cells, but did not alter the production of IL-2 by mouse splenic cells and human tonsil lymphocytes. Furthermore, the results also showed that triptolide at higher concentration had a slight inhibitory effect on the interaction of IL-2 and IL-2 receptors, and addition of exogenous IL-2 did not reverse the inhibiting action of triptolide on T-cell proliferation. Taken together, these results suggest that triptolide inhibits T lymphocyte proliferation mainly by affecting IL-2 receptor expression rather than IL-2 production. PMID- 7868295 TI - Adrenergic receptors regulate macrophage secretion. AB - Macrophages have been shown to possess both alpha 2 and beta 2-adrenergic receptors which appear to antagonize each other. The ability of these two kinds of receptors to mediate macrophage secretion was tested, using alpha- and beta antagonists, idazoxan and propranolol. Both antagonists could inhibit hydrogen peroxide and superoxide secretion, although the timing of the inhibition is different. However, only idazoxan has the ability to reduce nitrite accumulation, while propranolol fails to affect macrophage production. In addition, sodium nitrite was able to inhibit hydrogen peroxide and superoxide secretion, and hydrogen peroxide could reduce nitrite accumulation, suggesting that a negative cross-feedback mechanism exists. PMID- 7868296 TI - Methionine enkephalin combined with AZT therapy reduce murine retrovirus-induced disease. AB - AZT (7.5 or 15 mg/kg/dose) and the neuropeptide methionine enkephalin (Met-ENK, 1 or 3 mg/kg/dose) were used in a combined protocol for therapy of established murine retroviral infection. In both models used, Friend virus leukemia (FV) and BM5 complex (lymphadenopathy and immune deficiency), the drug combination was able to reduce mortality and splenomegaly. While increasing mean survival time of those animals that did not survive infection by FV, when compared to infected control mice or mice treated with AZT alone, Met-ENK used alone at 1 and 3 mg/kg/mouse had no effect in reducing morbidity or mortality due to either virus. This suggested that Met-ENK had no direct antiviral effect at the concentrations used. In fact, mice treated with either single drug therapy or the combination still yielded virus in their spleen, even when splenomegaly was absent. The data suggest that Met-ENK, which has been reported to be immunostimulatory, acts in combination to improve the efficacy of AZT in reducing progression of disease in murine retrovirus models for human AIDS. PMID- 7868297 TI - A novel type of B-cell mitogen isolated from juzen-taiho-to (TJ-48), a Japanese traditional medicine. AB - Juzen-taiho-to (TJ-48), a Japanese traditional medicine, is known to have various immunological activities including the induction of B-cell proliferation. We investigated the properties of the pectic polysaccharide fraction of TJ-48 (F-5 2) which is most active in the proliferation of spleen cells. To an extent equal to that of TJ-48, F-5-2 induced the proliferation of B-cells, particularly those holding both sIgM and sIgD. The proliferation induced by F-5-2 was T-cell independent and macrophage dependent. The macrophages could be substituted for a soluble factor(s) secreted from the macrophages but not for IL-1. Generally, B cell mitogens are known to induce the proliferation of B-cells and subsequently differentiation into plasma cells. However, although F-5-2 induced the B-cell differentiation, it arrested their development in the intermediate stage of the B cell differentiation. The B-cells induced by F-5-2 produced IgM antibody in response to IL-6 and an antigen (SRBC) but not IgG antibody. F-5-2 induced the expression of IL-6R not only on IgM+ and IgG+ B-cells but also on IgD+ B-cells. These results suggest that F-5-2 is a new type of B-cell mitogen. PMID- 7868298 TI - Suramin blocks the binding of interleukin-1 to its receptor and neutralizes IL-1 biological activities. AB - This report demonstrates the ability of the anti-cancer drug suramin to interfere with the binding of interleukin (IL)-1 to its receptor and to inhibit IL-1 induced biological activities. In a radioreceptor cell based assay, suramin inhibits the binding of IL-1 alpha to several murine cell lines expressing predominantly type I and type II IL-1 receptors. Affinity cross-linking experiments using IL-1 alpha and EL-4.6.1 cells confirms that suramin inhibits the binding of the ligand to the 80 kDa IL-1 type I receptor. In contrast, suramin fails to displace significantly prebound IL-1. In a cell-free system, suramin prevents the binding of IL-1 alpha and IL-1 beta to murine and human recombinant soluble type I IL-1 receptors. For example, the IC50 for suramin inhibiting IL-1 alpha and IL-1 beta binding to soluble human IL-1 receptor were 204 microM and 186 microM, respectively. The suramin analogues, NF-058 and NF-103 (which bear the same number of sulfate groups as suramin), are between three- and ten-fold less active than suramin in inhibiting IL-1 binding to EL-4.6.1 cells, and to recombinant soluble IL-1 receptor. Furthermore, in a dose-dependent manner suramin prevents several IL-1 mediated biological responses, including thymocyte proliferation, PGE-2 synthesis and IL-6 production. The inhibitory effect of the drug can be significantly reversed by the addition of excess cytokine. Taken together, the results indicate that suramin is a competitive IL-1 receptor antagonist. Because IL-1 participates in a broad range of immunological and inflammatory functions, the data suggest that suramin administration may influence important activities beyond those associated strictly with tumor inhibition. PMID- 7868299 TI - Functional inactivation of primary T-cells stimulated in vitro in the presence of cyclosporine. AB - Cyclosporine (CsA) blocks in vitro polyclonal activation of primary murine T cells in a complex manner. This cannot be completely reversed by exogenous IL2, and leads to a partial blockade in expression of the IL2 receptor (p55 chain) and, more intensely, in CD69. In proliferation assays, T-cells recovered from CsA treated cultures and washed free from CsA were markedly refractory to restimulation in the presence of fresh accessory cells. In cell titration restimulation assays, CsA-treated, but not control T-cells, were also markedly unresponsive to accessory cell-independent stimuli provided by immobilized anti CD3 antibody or rIL2, combined to phorbol ester. CsA-treated, but not control activated T-cells, undergo progressive cell death after drug removal and reculturing. In contrast, primary T-cells activated by a CsA-resistant pathway (rIL2 plus phorbol ester) and treated with CsA, did not develop unresponsiveness, compared to controls. When primary T-cells were stimulated with rIL2 plus phorbol ester in the presence of the calcium ionophore ionomycin, treatment with CsA resulted in marked unresponsiveness of the T-cells, compared to untreated controls. The data indicate that primary activation of T-cells in vitro in the presence of CsA induces an unresponsive state which lasts independent of the presence of CsA, and results in progressive cell death. We suggest that these effects could characterize one additional mechanism of CsA action in vivo. PMID- 7868300 TI - Depression of cytochrome P-450 in mouse liver induced by fractions from Nocardia opaca. AB - We measured the liver cytochrome P-450 content of mice 24 h after they had been injected with the following immunoadjuvants: Nocardia opaca derivatives and peptidoglycans from several bacterial strains. The cell wall fraction was not active, the others diminished liver cytochrome P-450 levels. The dose-response activity varied with the bacterial origin of the peptidoglycans. These findings indicate that the toxicity and efficiency of immunochemotherapeutic protocols can be modified by altering drug metabolism. PMID- 7868301 TI - Granulocyte defects and opioid receptors in chronic exposure to heroin or methadone in humans. AB - In order to elucidate better the immunological effect of opioid abuse in the absence of HIV infection as a confounding factor, granulocyte function was investigated in three groups of HIV-negative subjects, including 20 active parenteral heroin abusers (H), 20 long-term methadone-maintained former opiate abusers (M) and 20 healthy controls (C). Chemotaxis to N-formyl methionyl-leucyl phenylalanine (fMLP), casein and activated plasma were markedly and similarly reduced (approx. 50%) in both H and M groups, as was true for superoxide production after fMLP and PMA stimulation, 47% decrease of C values. Polymorphonuclear (PMN) of H and M subjects also exhibited a very marked and similar reduction in the expression of CD11b/CD18 integrin receptors after fMLP treatment, with values that were less than 10% of those in controls, as observed by flow cytometry. In parallel, PMN of H and M individuals presented an approximately four-fold increase in opioid receptors numbers compared to controls, a significant inverse correlation existing between the increase in opiate receptors and defective chemotaxis. The possible mechanism underlying the observed changes in PMN of H and M individuals is discussed. PMID- 7868302 TI - Protective effect of cobra venom factor on pulmonary injury induced by oleic acid. AB - The protective effect of cobra venom factor (CVF), separated from the venom of Naja naja atra, on pulmonary injury induced by oleic acid was reported. The blood gas tensions, tidal volume, transthoracic pressure and pulmonary arterial pressure in anaesthetized dogs were continually monitored. The experimental results showed that CVF, given 20 h before the dosage depleting complements exceed 95%, significantly attenuated oleic acid-induced pulmonary dysfunction, including hypoxemia, increasing veno-arterial shunt and P(A-a)O2 and decreasing dynamic compliance and pulmonary blood flow. Histological examination of lung tissues after the experiment also showed improvement of hyaline membrane formation, alveolar haemorrhage and pulmonary arteriolar thrombosis. It was evident that the depletion of serum complements by CVF inhibited the development of lung injury induced by oleic acid. CVF might be a potentially useful drug for the treatment of respiratory distress syndrome in the near future. PMID- 7868303 TI - Heterogeneity of growth and turnover in the femurs and humeri of calcium-replete and -deficient C57BL/6 and SENCAR mice at sexual maturity. AB - The effects of dietary calcium intake on the composition and turnover of the femur and humerus were compared in two mouse strains that differ in growth kinetics and phorbol ester-induced signal transduction. C57BL/6 (control) and SENCAR (large) mice were fed calcium-deficient (0.02% Ca) or -sufficient (0.6% Ca) diets from 10 to 14 weeks of age. Bone mass was determined gravimetrically. Calcium and magnesium were determined by atomic absorption spectrophotometry, while phosphorus was determined colorimetrically. Turnover was estimated pharmacokinetically in [3H]tetracycline-labeled bone. Femur and humerus lengths, breadths, masses, and ash and mineral contents were higher in SENCAR mice than in C57BL/6 mice at 10 weeks of age and after being fed 0.02% or 0.6% calcium diets for four weeks. Relative formation was higher in C57BL/6 mice than in SENCAR mice from 10 to 14 weeks of age, resulting in greater net increases (0.6% Ca diet) or lower net decreases (0.02% Ca diet) in the calcium contents of the femurs and humeri of C57BL/6 mice, compared to SENCAR mice. Calcium-deficient feeding stimulated higher relative rates of bone resorption in both strains and affected the net changes in bone calcium contents. Thus, hereditary factors in SENCAR and C57BL/6 mice that regulate formation rates, not resorption rates or the response to dietary calcium intake, appear to modulate net changes in humerus and femur calcium contents at maturity. PMID- 7868304 TI - Morphometric analysis of skeletal muscle growth in the high growth mouse. AB - The high growth phenotype in the mouse results from a single autosomal recessive locus (hg) mapped to chromosome 10, that produces a marked increase in growth rate and body size compared to controls. Using morphometric methods, we quantified skeletal muscle growth in newborn male and female high growth mice, and at 3, 6, and 9 weeks of age. Adult male high growth mouse body weights increased by 42% and muscle weights increased 39-43% compared to controls. Differences between high growth and control muscle weights were removed after normalization to body weight. Similar changes in muscle and body weights were found in female high growth mice. Muscle cross-sectional area was significantly (P < 0.05) increased in high growth mouse gastrocnemius (GAS), soleus (SOL), and tibialis anterior (TA) muscles at 6 and 9 weeks of age. Cross-sectional areas of slow type 1, and fast type 2b fibers were moderately increased in all high growth muscles measured. Muscle fiber number was increased by approx 30% in the high growth SOL, GAS and TA muscles. We conclude that rapid growth in the high growth mouse is accompanied by an increase in muscle mass, due to fiber hyperplasia and hypertrophy, and that the hg locus may act during myogenesis to alter the proliferation rate and/or fusion kinetics of high growth mouse muscle cells. PMID- 7868305 TI - Calcium homeostasis in in ovo and ex ovo turkey embryos. AB - Calcium homeostasis of in ovo (normal) and ex ovo (shell-less) turkey embryos was investigated at 15, 18, and 21 days of incubation. Hypocalcemia and an elevation in circulating 1,25(OH)2D3 in ex ovo embryos were observed by 15 days. Calcium and phosphorus concentrations in femora and tibiae in ex ovo embryos were significantly lower compared to their normal counterparts. These results suggest that shell calcium mobilization is required prior to 15 days of incubation for maintaining serum calcium and supporting bone mineralization. Furthermore, the elevation of 1,25(OH)2D3 is indicative of a functional calcium homeostatic mechanism responding to the absence of the primary calcium source (eggshell) during the second half of turkey embryonic development. PMID- 7868306 TI - Comparison of postnatal development of anterior latissimus dorsi (ALD) muscle in heavy- and light-weight strains of turkey (Meleagris gallopavo). AB - ALD muscle development was studied from day 2 to week 15 in males of two turkey strains. At 15 weeks, the heavy-weight (HW) strain weighted 2.2 times as much as the light-weight strain (LW). Morphometric and immunocytochemical analysis showed the presence of small fibers in HW ALD muscle which simultaneously accumulated ventricular and embryonic fast myosin heavy chain isoforms. The appearance of these nascent myofibers suggests that hyperplasia contributes to the growth of HW ALD muscle. PMID- 7868308 TI - 18th European Conference on Microcirculation. Rome, Italy, 4-8 September 1994. Abstracts. PMID- 7868307 TI - The role of plasma growth hormone, prolactin, triiodothyronine and tetraiodothyronine in the regulation of growth and sex differences in body weight of turkeys. AB - An attempt was made to alter male:female (M:F) body weight ratios in two strains (S12 and S72) of turkeys by selective matings; to study their post-hatching growth patterns and to relate growth patterns to plasma growth hormone (GH), prolactin (Prl), tetraiodothyronine (T4), and triiodothyronine (T3) concentrations. Selection for high and low M:F body weight ratio (HR and LR) was essentially ineffective in both strains. Sex differences in body weight were first significant in S12 at day of age and in S72 at 6 wk. Plasma GH and Prl rose during the first 2 wk of age and fell thereafter while T3 levels decreased and T4 levels increased over time. Differences in plasma hormones between lines and sexes within strains were noted, but showed no consistent patterns. Correlations between GH and growth were mostly negative. When significant, regressions between body weight and GH or gain and GH were generally negative. Significant correlations between Prl and body weight in males were negative whereas they were of mixed sign in females. Correlations between T3 levels from 2 to 8 wk of age and body weight over this same period were mostly positive in males whereas those at later ages and in females were mostly negative. Few significant correlations between T4 and weight were found. These findings suggest that the regulation of growth in turkeys is quite different than that of mammals and that hormones known to regulate growth in some species may not do so in others. PMID- 7868309 TI - IND: nurses focus on role in family health. PMID- 7868310 TI - US: nursing tied to lower mortality rates. PMID- 7868311 TI - Cairo conference promotes women's rights. PMID- 7868312 TI - Explaining long-term HIV survivors. PMID- 7868313 TI - The pension fund for nurses in Denmark. AB - As women and because of their job mobility and low wages, female nurses in many countries are among the employee groups most severely disadvantaged under pension schemes. For many national nurses' associations, an adequate and equitable pension income for nurses after retirement is a major concern. Below a report on the system the Danish Nurses' Organization secured for nurses in Denmark--a system that offers nurses the best possible pension conditions and support when ill and disabled--and on page 177 a summary of efforts by the American Nurses' Association to make a portable pension system for nurses a legal requirement for employers. PMID- 7868314 TI - American Nurses Association's strategy to enact a portable pension scheme. AB - The American Nurses Association has long been active in the issue of pension portability and sees several avenues: federal legislation, collective bargaining and public education. It is engaged in a project to examine all three options as well as try to gather much needed data on the specific situation nurses face in vesting in sound pension programmes. PMID- 7868315 TI - Connecting older female nurses' worklife issues to retirement. AB - What are the worklife issues of significance to older nurses and to what extent will they influence retirement decisions? In Canada, the recent push toward obtaining a baccalaureate degree before the year 2000 has resulted in extraordinary pressures for older nurses and brought about divisions within the profession--age and experience being important variables in this conflict. PMID- 7868316 TI - Linking research and practice. AB - Although nurses are expected to incorporate research findings into their practice and be accountable for their actions, they often lack support to carry out these professional responsibilities. Below, how a service agency facilitated the linkage between nursing research and practice at a Canadian hospital. PMID- 7868317 TI - Buffon's Histoire naturelle. History? A critique of recent interpretations. PMID- 7868318 TI - Ultra-orthodox Jewish attitudes towards mental health care. PMID- 7868319 TI - Religious patients' metaphors in the light of transference and countertransference considerations. AB - The verbal material of religious individuals in psychotherapy is laden with metaphors, folkloristic themes, and literary allusions whose meanings are generally deemed adequately elucidated by analysis of their symbolic content, generally in terms of the classic psychosexual conflict model. Contemporary psychoanalytic models demand that such material be further examined in terms of the level and quality of object relations and representation that characterize such content, and with an eye toward the influence of early, preverbal intersubjective factors that, by nature, tend to attain a minimal amount of psychic representation. These factors add richness and complexity to our overall understanding of the religious personality. The expanded role of countertransference as a tool for comprehending prerepresentational states, and the modes in which these are communicated, helps to outline new dimensions of religious object experience. PMID- 7868320 TI - The professional credo of an ultra-orthodox psychotherapist. AB - The somewhat unorthodox working guidelines and professional attitudes of an ultra orthodox (UO) psychotherapist are presented. Despite relatively low status in the UO society, the UO therapist can contribute much to UO society: by enhancing individuals' religious, as well as, general functioning, and by serving as a consultant to rabbinical and community leaders. Ensuing from the centrality of religion in the therapist's life, usual therapy norms and parameters may be abrogated or modified in the direction of increased stringency (eg, in avoiding sexual misconduct and subtle forms of "robbery") or leniency (eg, extra therapeutic helpfulness). It is noted that secular professionals who are knowledgable and respectful of religion are at no disadvantage in working with the UO. A culturally-sensitive approach is suggested when treating this population. PMID- 7868321 TI - The foundations of Judaism: psychoanalytic interpretations. AB - The psychological foundations of Judaism are a major challenge to psychoanalytic theory. This (selective) literature review focuses on post-Freudian work on this question. Freud described Judaism as a father religion, within the Oedipal framework of all religions and cultures. Over the years other notions have become dominant, and we can observe the changes from the Oedipal to the pre-Oedipal and towards more attention to maternal projections. Jewish mythology is a major topic, and the attention given to it bears no relation to its role in living Judaism. Many psychoanalytic contributions which aim at interpreting Judaic mythology demonstrate mostly their authors' inability to separate mythological narratives and history, as they accept without criticism the biblical account of supposedly ancient events, and then continue with speculations about mythological personages and events. The literature we have reviewed is certainly psychoanalytic, but one question is its relationship to Freud's work on religion. What emerges is that in many cases there is no attempt to follow Freud in the sense of accepting his assertions, but there is continuity in terms of interpretive temperament. Freud's writings have served as stimulus and inspiration, not as dogma to be upheld. PMID- 7868322 TI - The influence of cultural factors on obsessive compulsive disorder: religious symptoms in a religious society. AB - Judaism is one of many religions that demand cleanliness and exactness, inculcate the performance of rituals from childhood and view their non-performance as wrong or sinful. Rituals concerning cleanliness and exactness are the commonest presentations of OCD. In a sample of 34 psychiatric out-patients with OCD in north Jerusalem, religious symptoms were found in 13 of the 19 ultra-orthodox patients, and in one of the 15 non-ultra-orthodox patients. Nine of the 15 OCD patients with religious symptoms also had non-religious symptoms. Four main topics of religious symptomatology were found: prayer, dietary practices, menstrual practices and cleanliness before prayer. The dictates of religious codes regarding these topics are presented and the law is rigorous in its demands, in many cases encouraging repeating rituals. Nevertheless, repetitive performance of religious rituals is recognized by OCD sufferers and their rabbis as expressing psychopathology rather than heightened spirituality. The forms of the religious obsessions and the associated rituals in this sample were similar to the presentation of OCD in non-religious patients. Religion appears not to be a distinctive topic of OCD, rather it is the setting for the condition in very religious patients. PMID- 7868323 TI - Traditional psychotherapeutic healing and healers in the Palestinian community. AB - The aim of this paper is to offer some general observations about traditional psychotherapeutic healing and healers in the Palestinian community. Ten healers, known as sheikhs or sheikhas, were interviewed, and their statements comprise the principal data on which this study is based. Observations are offered regarding (1) the background, training and some characteristics of the healers; (2) characteristics of the patients and illnesses treated; (3) therapeutic techniques and treatment rationale. PMID- 7868324 TI - Is psychotherapy possible in unbelievers? PMID- 7868325 TI - Tourette's disorder. PMID- 7868327 TI - Treatment of childhood migraine with autogenic training and skin temperature biofeedback: a component analysis. AB - Using a controlled group outcome design, skin temperature biofeedback with autogenic training and autogenic training only was compared to a waiting list as a treatment for childhood headache. Thirty children with migraine headaches, ages 7 to 18 years were randomly assigned to one of the three conditions. Statistical analyses of headache activity indicated that children in the treatment groups improved in headache frequency and duration but not intensity as compared to the waiting list control group. These findings were consistent through a 6 month follow-up. In terms of clinical improvement, 80% of the biofeedback group, 50% of the autogenics group, and none of the waiting list control group were symptom free. These findings were discussed in relation to past childhood headache studies and implications for current treatment of children with headaches. PMID- 7868326 TI - Clinical and angiographic features of thunderclap headache. AB - Thunderclap headache is an acute high intensity headache similar to that seen in the setting of ruptured saccular aneurysm. We report four patients without subarachnoid hemorrhage who presented with thunderclap headache. Three patients had transient neurologic signs or symptoms. Cerebral angiography revealed diffuse segmental intracerebral arterial vasoconstriction which was reversible in the one patient in whom angiography was repeated. The headaches resolved spontaneously in all cases and after 1 week did not recur. These cases highlight the specific clinical and angiographic features and the self-limited course of patients with thunderclap headache and suggest that thunderclap headache may represent a unique headache category. On the basis of these cases and others reported in the literature, we propose diagnostic criteria for thunderclap headache. PMID- 7868328 TI - Serum and red blood cell magnesium levels in juvenile migraine patients. AB - Recently an important role for magnesium in establishing the threshold for migraine attacks has become evident. Accordingly, we measured serum and red blood cell magnesium levels in juvenile migraine patients with and without aura interictally. In comparison with normal subjects, migraineurs had significantly lower serum and red blood cell magnesium levels. PMID- 7868329 TI - MMPI and critical flicker frequency (CFF) analysis in headache patients with and without drug abuse. AB - Sixty-three headache patients (migraine: n = 28; tension-type headache: n = 35) who fulfilled the IHS criteria of 'drug abuse' were investigated by means of the Minnesota Multiphasic Personality Inventory (MMPI) and the Critical Flicker Frequency (CFF) analysis. The results were compared to those of 63 headache patients without drug abuse (matched-pair case-control study). With respect to the MMPI results, no statistically significant differences between patients with drug abuse and patients without drug abuse were found. However, patients with drug abuse showed significantly decreased CFF values compared to patients without drug abuse. This was true both for patients with migraine and for patients with tension-type headache. Thus, CFF analysis may serve as a useful method to differentiate between headache patients with drug abuse and those without drug abuse. PMID- 7868330 TI - Postangiography headache. AB - In order to study the frequency and characteristics of post-angiography headache, we interviewed 45 consecutive patients (mean age +/- SD = 57 +/- 15 years; M/F = 15/30) who underwent transfemoral cerebral angiography for: ischemic cerebrovascular disease (n = 33); suspected arteriovenous malformations (n = 4; one confirmed); suspected cerebral aneurysm (n = 5; two confirmed); and arterial dissection (n = 3; one confirmed and one was a follow-up study of a previously demonstrated dissection). Postangiography headache developed in 15 (33%) patients, 125 +/- 99 min after the completion of the study. It was unilateral in nine (60%) patients, homolateral to the usual side of migraine headache in two or three migraineurs, and pulsating in six (40%). Nausea, vomiting, photophobia, and phonophobia accompanied postangiography headache in 20%, 7%, 33%, and 20% respectively. Postangiography headache fulfilled the International Headache Society criteria for migraine without aura (except for the number of attacks) in 27% of patients. Patients with and those without postangiography headache were comparable in mean age, sex, and indication for angiography. Fifty-three percent (8/15) of patients with postangiography headache and 23% (7/30) of the non postangiography headache group reported prior recurrent headaches (P = 0.047, likelihood ratio chi-square). Postangiography headache has the characteristics of delayed arterial pain which may be related to a catheter-induced or contrast dye induced release of vasoactive substances, notably nitric oxide and serotonin. PMID- 7868331 TI - Headache and quality of life. AB - The present prospective-type study quantified, by way of and ad hoc questionnaire, the impact of the headache attack in its various manifestations and the effect of headache on the quality of life of 400 headache sufferers. In addition, the functional status of episodic headache patients has been compared to that of patients with chronic daily headache. We observed that during headache attacks, episodic headache patients were significantly more disabled by physical symptoms. On the contrary, patients with chronic daily headache showed a significantly greater occurrence of emotional disturbances. A difference was detectable for mental health which was significantly more compromised in chronic daily headache than in episodic headache patients (P < 0.05). During the interictal period, quality of life appeared more compromised in chronic daily headache than in episodic headache patients. Chronic daily headache subjects were characterized by higher disability scores in all the sections considered. The results of this investigation confirm that headache negatively influence a patient's quality of life not only during attack phases but also during interictal periods and underline the importance that future studies on the efficacy of headache treatments should also evaluate the impact on patient's quality of life. PMID- 7868332 TI - Secondary syphilis and headaches. AB - Secondary syphilis is associated with headaches. We describe two patients with headache from secondary syphilis and we recommended considering this in the differential diagnosis and evaluation of the headache patient. PMID- 7868333 TI - Provocation of unilateral pain in cluster headache patients by breathing CO2. AB - Ten patients with cluster headache in an active period and 6 controls were studied as to heart rate, blood pressure, blood flow in the common carotid arteries (CCA), end-tidal PCO2 and pain before, during and after 6 minutes of breathing 6% CO2 in air. Heart rate increased significantly during CO2 breathing in controls but not in patients. The cluster headache patients had significantly lower baseline end-tidal PCO2 than controls. CCA blood flow increased significantly during CO2 breathing in both groups. Vascular resistance decreased during CO2 provocation and increased above baseline levels 5 minutes after provocation in both groups and related to the end-tidal PCO2. Six of eight cluster headache patients, who had an increase of blood flow at provocation, reported slight to moderate unilateral pain in relation to the CO2 provocation in contrast to controls. One patient treated with 6 mg sumatriptan 2.5 hours before the provocation had an end-tidal PCO2 within the range of the controls, and did not get an increase of CCA blood flow or pain at provocation. Six of the cluster headache patients were restudied when out of the active period. There was still no heart rate increase during CO2 breathing and end-tidal PCO2 was still lower than in the controls. Unilateral headache was not provoked. PMID- 7868334 TI - Headache due to an extra joint between head and neck. AB - A girl, born in 1973, started having headache in preschool age. After a head trauma in 1985, there was a clear worsening of the headache, and the headache became chronic at around 14 years, making regular school attendance impossible. The headache was "symptom poor," bilateral-occipital, but with a clear left-sided preponderance and occasionally spreading to the forehead. The headache was always worst in the morning hours, easing up by noontime. Neck rotation to the right could provoke long-lasting exacerbations. Neck movement was restricted on rotation to the left. A sore bony structure was discovered on palpation just underneath the mastoid process of the left side. This proved to correspond to a bony "bridge" with an extra joint between the first vertebra on the left side and the skull, medially to the mastoid process that could be demonstrated on x-ray tomography and CT scanning. This bony bridge was removed surgically more than 2 years ago, and the pain disappeared on the day of operation and has not recurred in the intervening time. Such bony bridges have in the past been considered to be innocuous and not symptom producing. Although this may be the general rule, the present case tends to show that even to this rule, there are exceptions. PMID- 7868335 TI - Cluster-like headache in a patient with a trigeminal neurinoma. AB - We report a case of cluster-like headache in a patient with a trigeminal neurinoma. Symptomatic cluster headache was suspected because of the absence of typical periodicity and the persistence of background headache. Magnetic resonance imaging findings were consistent with a trigeminal neurinoma. PMID- 7868336 TI - Intravenous DHE and cost saving. PMID- 7868337 TI - DHE and post-concussion syndrome. PMID- 7868338 TI - Hemodynamic changes in cluster headache. PMID- 7868339 TI - Verapamil and cluster headache. PMID- 7868340 TI - Analgesic rebound headaches. PMID- 7868341 TI - Headache formulary for managed care organizations. PMID- 7868342 TI - Anger, depression, and disability: a path analysis of relationships in a sample of chronic posttraumatic headache patients. AB - Anger and depression are common affective concomitants of chronic headache. Previous research suggests that the affective component of headache may contribute to the patient's perceptions of the degree to which the headache is disabling. The present study examined the relationship between anger expression, anger suppression, depression, and headache-related disability (interference with function) in a sample of chronic posttraumatic headache patients. A path analytic model indicated a direct relationship between depression and perceived disability. Anger suppression and anger expression each had a direct influence on depression, but their effects on disability were mediated through depression. The results partially replicate a previous path analytic study of the relationships among these variables in a chronic headache sample. PMID- 7868343 TI - The characteristics of respite patients. AB - A prospective study of planned respite admissions, comparing them to admissions to continuing care. The characteristics, dependency and CAPE scores of each patient were noted, as was medical intervention during the respite admissions. Twelve month follow-up provided data on long-term prognosis. Fifty three (30 females) respite patients; mean age 80.3 years (range 63-97) were compared with 31 (18 females) continuing care patients; mean age 82.6 (range 74-94). There was no difference in the physical dependency between the two groups, except that continuing care patients were significantly more incontinent of urine and had significantly worse cognitive function. Only eight (15%) respite patients needed medical intervention during their admission and one patient died. One year follow up revealed that 26% of respite patients had died against 48% of continuing care patients (p < 0.01). A further 33% of respite patients had been admitted to institutional care. PMID- 7868344 TI - The role of health visitors in the prevention of home accidents involving children: time for a rethink? AB - Home accidents involving children are an important public health problem in developed and developing countries. There is uncertainty concerning the effectiveness of different approaches to child home accident prevention, and a need to evaluate current practice. This paper reports the findings of an interview survey of all 57 health visitors working in Clydebank and the north west area of Glasgow, concerning their role in child home accident prevention. Their role consisted mainly of education of children and families in home safety, using face-to-face discussion and leaflets. Forty-seven per cent of health visitors reported difficulty in raising home safety issues with families. Ninety four per cent did not think that the educational approach had been effective in reducing child home accidents and in improving home safety behaviour of families. This poses the question of whether the time of health workers and health service resources should be invested in alternative approaches. PMID- 7868345 TI - Multi-disciplinary guideline development: a case study from community pharmacy. AB - There is increasing interest in the role of clinical guidelines to encourage appropriate care. However, if guidelines are to achieve this, they need to be scientifically valid in the sense that, when followed, they lead to the health gains projected from them. Multi-disciplinary involvement in guideline development is desirable and is likely to promote validity. However, there are difficulties inherent in multidisciplinary guideline development relating to professional hierarchies and mutual ignorance of different professionals' skills and modus operandi which have not previously been addressed in the literature. In this paper, we describe in detail the processes involved in the multidisciplinary development of guidelines for community pharmacy management of dyspepsia and discuss the practical issues and problems encountered. PMID- 7868346 TI - Influence of clinical resources on the treatment of intermittent claudication. AB - Management of intermittent claudication varies between surgeons, even after adjustment for case-mix, and could be related to the availability of clinical resources. The aim of this study was to ascertain whether vascular surgeons perceived deficiencies in the resources available to them for the management of claudication and to determine whether an association existed between reported deficits and patient management. Over a six month period, 28 vascular surgeons in Scotland completed recording forms on their treatment intentions for 1,180 claudicants. Subsequently, the surgeons were interviewed about resources available for vascular surgery. The majority of surgeons reported deficiencies in resources, predominantly insufficient operating lists (71%) and staff shortages (71%). Although considered less important than clinical factors or patient wishes, resources were independently associated with treatment. Surgeons reporting insufficient operating lists were less likely to opt for surgical treatment (p < 0.05), and those working with reluctant or inexperienced radiologists were less likely to consider percutaneous transluminal angioplasty (p < 0.05) and more likely to offer surgery (p < 0.001). However, case-mix and resources explained only some of the variations in treatment. The residual variation was likely to reflect an underlying lack of agreement among surgeons on the most appropriate management of claudication. Randomised controlled trials to address this issue would be welcomed by the majority of surgeons questioned. PMID- 7868347 TI - A national service for the brain-injured with severe behavioural disturbance- referrals, treatment and outcome in the first two years. PMID- 7868348 TI - The management of carcinoma of the vulva: current opinion and current practice among consultant gynaecologists in Scotland. AB - A postal questionnaire survey of all 126 consultant gynaecologists in Scotland was undertaken in order to obtain an overview of current opinion and current practice in relation to the management of vulval carcinoma. The response rate was 95%. Fifteen suggested criteria for good quality care were validated by a balance of agreement among respondents. There was particularly strong agreement (> 90% of respondents) that vulval carcinoma should be managed by subspecialists rather than generalists, that en bloc radical vulvectomy is not always required, that patients should be informed of their diagnosis and that long-term follow-up is required. There was least agreement (< 50% of respondents) that groin lymphadenectomy may be omitted in selected cases and that follow-up need be at special multidiscipline clinics. An encouraging picture of current practice emerged. Very few consultants who do not profess to be oncology subspecialists would manage cases alone, few perform en bloc radical vulvectomy in all cases and few undertake deep pelvic lymphadenectomy. Most acknowledge the importance of psychosexual issues and all generally inform patients of the nature of their diagnosis. The postal questionnaire approach achieved a good response rate and has provided an informative overview of current opinion and practice on a national basis. This approach may be more valuable than case-note review audit in providing a meaningful picture of contemporary practice for uncommon conditions like vulval cancer. PMID- 7868349 TI - Preliminary analysis of the care of injured patients in five Scottish teaching hospitals: first report from the Scottish Trauma Audit Group (STAG). AB - In 1991, the Scottish Trauma Audit Group (STAG) was established to measure the effectiveness of management of major trauma. A review of the care of seriously injured patients admitted to five teaching hospitals was undertaken. Information on 3,790 patients admitted for three days or more, transferred, admitted to an intensive therapy unit or who died from their injuries, was held on computer at the end of August 1993. The outcome of 1,418 cases was assessed objectively using an injury scoring system and compared to national norms. Mortality for patients sustaining blunt trauma was not significantly better or worse than the average standard of clinical care predicted from a UK database. Differences were noted in the performance of the five centres, and two of the hospitals had a significantly higher mortality that that predicted from a comparable North American dataset. There would appear to be delays in transferring seriously injured patients from the scene and in providing experienced staff and timely operations in hospital. The management of seriously injured patients in major centres in Scotland could be improved upon significantly. PMID- 7868350 TI - A review of influenza immunisation in Lothian. AB - OBJECTIVES: To assess the influence of the Chief Medical Officer's annual guidelines on influenza immunisation and to estimate vaccine uptake particularly of those resident in long-stay residential facilities and of other recommended at risk groups. DESIGN: Postal questionnaires. SETTING: Lothian, Scotland (population 750,000). SUBJECTS: All consultants caring for patients in long stay National Health Service facilities; a random sample of all general practitioners (GP's) in Lothian; managers/charge nurses of all local authority, private and voluntary long stay facilities in Lothian and continuing care facilities in the National Health Service including adults and children. MAIN OUTCOME MEASURES: Number (%) of general practitioners offering influenza vaccine to at-risk groups as defined in the Chief Medical Officer's guidelines; number (%) of hospital consultants caring for long-stay patients in hospital in Lothian who offer influenza vaccine to the same at-risk groups; percentage of long-stay residents/patients who received influenza vaccine in 1992-3. RESULTS: Seventy nine (75%) GPs said they offered influenza vaccine to all at-risk groups; 15 (14%) GPs said they did not care for patients in long-stay facilities but offered vaccine to the other at-risk groups; 12 (11%) GPs who did have long-stay residents on their list, offered vaccine to some of them only and to all other at risk groups; 14 (56%) hospital consultants did not offer influenza vaccine to long-stay patients; 10 (40%) immunised only those at risk from chronic medical conditions if their quality of life was good; 1 (4%) consultant offered vaccine to all long-stay patients. In the winter of 1992-3, the mean proportion of residents immunised in private nursing homes was 65%, in residential homes 68.5%, and in long-stay National Health Service wards 4.5%. GPs commented that annual publicity was confusing for the public, vaccine was not available at the right time and there was uncertainty on the efficacy of the vaccine. Hospital consultants were reluctant to immunise patients with a poor quality of life or who were demented and unable to give consent. CONCLUSIONS: A large majority of GPs followed official advice and offered influenza vaccine to long-stay patients and other at risk groups. Hospital consultants offered influenza vaccine only to a small proportion of their long-stay patients, primarily those with a good quality of life. PMID- 7868351 TI - The chief scientist reports ... An analysis of patients attending two emergency dental clinics in Edinburgh. AB - Two studies of self-referred patients attending emergency dental clinics in Edinburgh have shown that almost half of the patients have been to the dentist in the last year and 60% had routine treatment on their last dental visit. Despite this contact with dental services, over 40% of patients with a dental emergency who attend the emergency dental clinics say that they do so because of actual or perceived difficulty in obtaining immediate care from the general dental services. Some 17% attend the clinics for reasons of convenience and 19% of patients attend the emergency clinic at the Dental Hospital because they prefer to be treated in a 'centre of excellence'. In September 1994 the School of Dentistry is to close and the Dental Hospital relocated. Changes may have to be made to the organisation of general dental practice in the Edinburgh area to accommodate patients with a dental emergency. The majority of emergency dental patients in Edinburgh are not put off attending for the relief of their problem by the cost of National Health Service treatment. PMID- 7868352 TI - Changes in laminin immunoreactivity as a marker for the state of liver preservation. AB - In order to examine the role of the extracellular matrix glycoprotein laminin as a marker for the preservation of liver tissue, dog livers were perfused and then preserved for 5 min, 1, 2, 4, 6, 8, 10, 12, 22 and 26 hours with HTK (histidine tryptophan-ketoglutarate) solution at 5 degrees C and at 25 degrees C and with UW (University of Wisconsin) solution at 5 degrees C. The tissue was processed for the immunohistochemical demonstration of laminin using an anti-P1 and an anti-E8 antibody. The peroxidase-antiperoxidase method was used for the visualization of the immunohistochemical reaction. At the beginning of the preservation, immunostaining was observed for both fragments of laminin around bile ducts and blood vessels of the portal spaces, under all preservation conditions. Clear immunostaining was also visible in the wall of the terminal arterioles located between the liver lobules. In the 5 degrees C-preserved tissues, immunostaining for both laminin fragments occurred for preservation times between 4 and 6 hours in the form of isolated perisinusoidal deposits at the transition point where the sinusoids sprout from the terminal venules. In the 25 degrees C-preserved tissue, such a staining pattern was already visible after 1 to 2 hours, preservation time. Our results show that the occurrence of laminin immunoreactivity in the sinusoids can be taken as a marker for the state of liver preservation. A hypothesis for the presence and the role of this glycoprotein in the perisinusoidal space is presented. PMID- 7868353 TI - Localization of lipoprotein in pre- and post-transition atherosclerotic lesions following short-term incubation with [125I]LDL. AB - Ultrastructural autoradiography has been used to test the hypothesis that atherosclerotic regions of vessels differ with respect to lipoprotein uptake and localization. White Carneau pigeons, in which the prevalence and localization of aortic lesions are highly predictable, were fed a 0.25% cholesterol-supplemented diet to accelerate atherosclerosis. One hour prior to necropsy the birds were given a single intravenous injection of homologous [125I]LDL (low-density lipoprotein). Plasma die-away and tissue distribution of label were determined, and after the birds had been killed, the aortas, spleen and liver were processed for electron microscope autoradiography. Initial [125I]LDL uptake was rapid, with 35% of the label removed within 30 min. Predominant accumulation was in the liver, followed by the lung, kidney, the spleen and the aorta, in which the [125I]LDL level was approximately 4% that of the liver. Autoradiographic analysis documented hepatocyte (33%) and Kupffer cell (19.9%) localization in the liver and reticuloendothelial cell (57.4%) localization in the spleen. The aortic analysis involved serially sectioned lesions for direct comparison of non-lesion, lesion/non-lesion interface (edge) and deep lesion regions. Analysis of 2275 silver grains documented a ten-fold increase in LDL accumulation at the lesion edge (as compared to adjacent non-lesion) where macrophage foam cells contained more than 70% of the label. The other 30% was distributed equally among endothelium, the intimal matrix and smooth muscle cells. This distribution changed with more complex (deeper) lesions, although grain density in the complex lesions was comparable to the edge. In the complex regions, macrophage foam cell grains were reduced to 37%, whereas smooth muscle cell (22%) and the extracellular matrix (24%) label were both increased. These studies substantiate enhanced accumulation of lipoprotein specifically at lesion sites in the aorta and demonstrate a shift from macrophage localization at the developing edge to smooth muscle cell and the extracellular matrix in more complex deeper lesions. PMID- 7868355 TI - Phenolsulphotransferase: localization in kidney during human embryonic and fetal development. AB - The aim of our study was to localize phenolsulphotransferase (PST) in the developing mesonephric and metanephric kidneys of the human embryo and fetus using immunohistochemical methods with an antibody preparation recognizing members of the human phenolsulphotransferase enzyme family. In embryonic and early fetal development of the metanephric kidney, PST is located primarily in derivatives of the ureteric bud such as the ureter, pelvis, calyces and collecting ducts. This predominance declines by mid-fetal life: first, as nephrons evolve and develop they become increasingly PST-immunoreactive such that in mature metanephric kidney, the proximal tubules are highly PST-reactive, with other elements of the nephron also immunopositive (albeit at lower reactivities) and secondly, with the formation of an immunonegative transitional epithelium in ureter, pelvis and calyces, the reactivity retained in collecting ducts is only a small proportion of the total. The distribution of PST immunoreactivity is relatively uniform in proximal tubular cells throughout development, in contrast to collecting ducts, where, in fetal life, this reactivity is displaced to apices and bases by intracellular glycogen deposits. Mesonephric kidney tubules and the mesonephric duct are PST-immunoreactive and although mesonephric immunopositivity overlaps with that in the developing metanephric kidney the renal contribution to sulphation is absent or low at a time when the developing conceptus is most vulnerable to the potential toxic effects of teratogens. PMID- 7868356 TI - Retrograde neuronal tracing with cholera toxin B subunit: comparison of three different visualization methods. AB - In this report a comparison is made of three different visualization methods of rat cervical motoneurons retrogradely labelled with cholera toxin B subunit (CTb). CTb conjugates such as CTb-HRP and CTb-FITC or CTb-TRITC, which can be visualized after histochemical detection and by fluorescence microscopy, respectively. The following results were obtained. (1) Immunochemical detection of CTb with peroxidase and DAB-Ni incubation provides the best labelling of the cell bodies and their processes, whereas immunochemical detection with FITC produces less effective labelling of the dendrites. (2) Histochemical visualization of CTb-HRP conjugate gives results similar to those of CTb immunochemistry but produces a much more granular appearance of the label, which may affect the identification of distal dendrites. In addition, direct electron microscopic analysis of labelled structures can be achieved. (3) CTb-FITC and CTb TRITC visualization permit double-labelling experiments but the labelled cells exhibit fluorescence only in their somata and proximal dendrites. (4) Factors other than labelling intensity, e.g. double-labelling, preservation of the label, compatibility with other techniques and even economic reasons must be taken into consideration when a selection of visualization methods is to be made. PMID- 7868354 TI - Co-expression of collagen types II and X mRNAs in newly formed hypertrophic chondrocytes of the embryonic chick vertebral body demonstrated by double fluorescence in situ hybridization. AB - Collagen types II and X mRNAs have been demonstrated simultaneously in newly formed hypertrophic chondrocytes of embryonic chick vertebral cartilage using a double-fluorescence in situ hybridization technique. Digoxigenin- and biotin labelled type-specific collagen II and X cDNA probes were used. In the embryonic chick vertebra at stage 45, two different fluorescence signals (Fluorescein isothiocyanate and Rhodamine)--one for collagen type II mRNA, the other for type X mRNA--showed differential distribution of the two collagen mRNAs in the proliferating and hypertrophic chondrocyte zones. Several layers of newly formed hypertrophic chondrocytes expressing both collagen types II and X genes were identified in the same section as two different fluorescent colour signals. Low levels of fluorescent signals for collagen type II mRNA were also detected in the hypertrophic chondrocyte zone. Cytological identification of maturing chondrocyte phenotypes, expressing collagen mRNAs, is easier in sections processed by non radioactive in situ hybridization than in those subjected to radioactive in situ hybridization using 3H-labelled cDNA probes. This study demonstrates that double fluorescence in situ hybridization is a useful tool for simultaneously detecting the expression of two collagen genes in the same chondrocyte population. PMID- 7868357 TI - Lectin binding pattern in normal human labial mucosa. AB - The pattern of lectin binding in normal human labial mucosa was examined by light and electron microscopy using eight different lectins (ConA, LCA, WGA, UEA-1, RCA 1, SBA, DBA and PNA) and compared with the patterns in normal human skin and oesophageal mucosa. As seen by light microscopy, ConA, LCA, and WGA stained cell membranes in all layers of the mucosae. RCA-1 stained the plasma membrane of cells in the basal and middle layers, whereas cells in the superficial layers showed little positive staining. UEA-1, SBA, and PNA stained the cells in the middle layers weakly in some cases. No positive staining for DBA was seen. By electron microscopy, reaction product indicating ConA-binding sites was observed in the plasma membrane, cisternae of the endoplasmic reticulum, nuclear envelope and the Golgi apparatus. Binding of LCA, WGA, and RCA-1 was observed in the plasma membrane. These results show that the binding pattern of PNA, SBA, and RCA 1 in labial mucosa is different from that in the normal skin or oesophageal mucosa, although the labial mucosal epithelium, epidermis, and oesophageal epithelium are all stratified squamous epithelia. These differences in the cell surface sugar residues are likely to be related to the possible functional differences in these tissues. PMID- 7868358 TI - Annual Symposium of the Czech Society of Histochemistry and Cytochemistry. Brno, Czech Republic, August 30-September 2, 1993. Abstracts. PMID- 7868359 TI - Detection of manganese superoxide dismutase mRNA in the theca interna cells of rat ovary during the ovulatory process by in situ hybridization. AB - To determine the possible involvement of reactive oxygen species in ovulation, dynamic aspects of superoxide dismutase (SOD) isozyme were studied in the ovaries of rats by in situ hybridization histochemistry. Previously, mRNA levels of ovarian manganese superoxide dismutase (Mn-SOD) were reported markedly to increase whilst enzymic activity of Mn-SOD decreased during the ovulatory process after treating immature rats with 10 and 5 Units, respectively, of pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (HCG). Levels of Cu/Zn-SOD activity and Cu/Zn-SOD mRNA were reported to remain unchanged throughout ovulation. This increase in the Mn-SOD mRNA level was shown in the present study by in situ hybridization to be localized to the theca interna cells throughout the PMSG/HCG-induced ovulatory process. The observations suggest that the turnover rate of Mn-SOD but not Cu/Zn-SOD increases specifically in the mitochondria of these cells. SOD has been postulated to play important roles in steroidogenesis. The relationship is discussed between mitochondrial functions in steroid-secreting cells and superoxide radicals and related metabolite(s). PMID- 7868360 TI - Computer-aided image analysis applied to immunogold-silver staining: evaluation of proliferating cell nuclear antigen (PCNA)-reactive sites in paraffin sections. AB - Feasibility of the combination of the immunogold-silver staining method (IGSS) and computer-aided image analysis was assessed for the detection of antigen in an immunostained, paraffin-embedded section. Using low-temperature IGSS, we stained a specimen of human oral squamous cell carcinoma with a monoclonal antibody, PC 10, against a proliferating cell nuclear antigen (PCNA/cyclin), and the section was analyzed by ACAS 570 interactive laser cytometry. The PCNA-positive cells, exhibiting a heteromorphic texture, were contrasted by the dark staining of their nuclei, but showed heterogeneity in staining intensity from cell to cell. Using a conventional microscope light source rather than a laser, and by employing the COMPLEMENT DATA program (which permits inversion of the data values) installed in the ACAS 570 software system, we were able to obtain a 'complemental image' which replicated the real immunohisto-morphology. Approximately 30-35 cells from three different areas in the same section were selected by DEFINE CELL and MARK AREA programs, and quantitative image analysis was performed in terms of cell integrated value, area, perimeter, and shape factor indicated in histogram form. The combined utilization of IGSS with computer-aided image analysis was demonstrated to offer a crucial advantage for the quantitative assessment of immunostained sections. PMID- 7868361 TI - 1,25-Dihydroxyvitamin D3 and 22-oxa-1,25-dihydroxyvitamin D3 in vivo nuclear receptor binding in developing bone during endochondral and intramembranous ossification. AB - Target cells for 3H-labeled 1 alpha, 25(OH)2 vitamin D3 [1,25(OH)2D3, vitamin D] and its analog 3H-labeled 22-oxa-1 alpha, 25(OH)2 vitamin D3 (OCT) have been identified during endochondral and intramembranous ossification in developing, undecalcified, unembedded bone, using thaw-mount autoradiography. Two-day-old neonatal rats were injected with [3H]1,25(OH)2D3 or [3H]OCT; after 2 h leg, spine, and head were frozen and sectioned. In the epiphyseal-metaphyseal region specific nuclear concentrations of [3H]1,25(OH)2D3 and [3H]OCT were observed in identical cell populations, being low in cells of the articular and resting zone, intermediate in the proliferating zone, and highest in hypertrophic chondrocytes and in osteoblasts and precursor cells. In the primary spongiosa intertrabecular spaces there were a large number of cells with nuclear labeling--probably osteoblasts and precursor cells. In contrast, in the secondary spongiosa intertrabecular spaces, apparent blood-forming cells were mostly unlabeled. Osteoblasts along bone spicules and compact bone in long bones, vertebrae, and head also showed strong nuclear labeling, as did cells of the periosteum. These data suggest that 1,25(OH)2D3 and OCT regulate development, differentiation, and activities of chondrocytes and osteoblasts, including differentiation of resting chondrocytes into proliferating and hypertrophic chondrocytes that involve "chondroclastic" enlargement of lacunae and "trans-differentiation" of surviving hypertrophic chondrocytes; differentiation of stroma cells into osteoblasts; and in periosteum and other regions of intramembranous ossification differentiation of precursor cells and osteoblasts. Nuclear receptor binding and their selective and hierarchical distribution during cell differentiation appear to correspond to multiple genomic effects toward growth, regeneration and repair. The findings indicate a physiological significance and therapeutic potential of 1,25(OH)2D3 and in particular of its less hypercalcemic analog OCT. PMID- 7868362 TI - Gonadotropin releasing hormone (GnRH) neurons project to growth hormone and somatolactin cells in the steelhead trout. AB - Analysis of gene expression using gonadotropin-releasing hormone (GnRH) antisense oligonucleotide confirmed by immunocytochemical localization the occurrence of GnRH neurons along the nervus terminalis in the steelhead trout (Oncorhynchus mykiss). Double-label immunocytochemistry revealed the distribution of mammalian (m), salmon (s) and chicken II (cII)-type GnRHs and various pituitary hormones. Both sGnRH and mGnRH appeared to be colocalized in the same cells of the nervus terminalis. Chicken GnRH II-immunoreactivity was found only in fibers and terminals. In the younger fish [73 and 186 days after fertilization (DAF)] GnRH neurons were seen rostral to the olfactory bulb. A novel GnRH ganglion, along the nervus terminalis, was found at the cribiform bone (gCB). A few non immunoreactive rounded cells were seen among the GnRH neurons. A second smaller ganglion was seen at the most rostrally located part of the ventromedial olfactory bulb (gROB). In the older fish (850 DAF) GnRH neurons were also observed in the basal forebrain. A small group of neurons (2-3 cells), at the caudoventromedial border of the olfactory bulb, formed the ganglion terminale. Occasionally isolated GnRH-immunoreactive cells were seen at the base of the olfactory epithelium, along the ventromedial margins of the olfactory nerve. GnRH immunoreactive and GnRH mRNA expressing neurons were absent from midbrain regions at the ages observed. GnRH-immunoreactive fibers were present only in older fish. The pattern of distribution of fibers that were immunoreactive to all three forms of GnRH was identical. Fibers were seen along the medial side of the olfactory nerve, throughout the brain and in the pituitary, associated with growth hormone and somatolactin cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868363 TI - Purification and immunoelectron microscopic localization of cellular glutathione peroxidase in rat hepatocytes: quantitative analysis by postembedding method. AB - To measure quantitatively the intracellular distribution of cellular glutathione peroxidase (GPX) in rat hepatocytes, ultrathin sections were stained by a postembedding immunogold technique. GPX had a specific activity of 1670 Units/mg protein, and was purified 2050-fold from rat liver by means of heat denaturation, ammonium sulfate fractionation, and a series of chromatographic procedures including thiol-Sepharose 4B. The purified GPX was shown to be electrophoretically pure, and was a homotetramer of 22 kDa subunits. Monospecific polyclonal antibodies were raised in rabbits by immunization. By immunoblot analysis, both the light mitochondrial the and cytosolic fractions of rat liver homogenate gave a single band with an identical mobility to that of the purified enzyme. Under the light microscope, hepatocytes showed nuclear staining and granular cytoplasmic staining, corresponding to certain intracellular structures. The labeling density (number of gold particles/microns 2) for GPX obtained by immunoelectron microscopy was 11.9 in the nuclei, 19.6 in mitochondria, 3.32 in peroxisomes, 1.95 in lysosomes, and 9.81 in the cytoplasmic matrix. These results suggest that cellular GPX is present in various compartments of rat hepatocytes, and that the GPX occurs in relatively higher amounts in mitochondria. PMID- 7868364 TI - The behaviour of nuclear domains in the course of apoptosis. AB - Programmed cell death is activated, by different stimuli and in many cell types, to regulate cell population balance during tissue proliferation and embryogenesis. Its initial event seems to be, in most cases, the activation of a Ca(2+)-dependent endonuclease, causing DNA cleavage into nucleosomic fragments. Its morphological expression is characterized by deep nuclear changes, consisting of typical cap-shaped chromatin marginations, followed by nuclear fragmentation and final formation of numerous micronuclei. Cytoplasmic damage appears in a very late stage of the process and the greatest part of the phenomenon appears to take place despite good preservation of the plasma membrane and organellar component. In the present study we analyzed apoptosis in camptothecin-treated HL60 leukaemia cells, and in freshly isolated mouse thymocytes treated with dexamethasone. The process was first quantified and time monitored by flow cytometry. Subsequently the specimens were processed for morphological examination in order to investigate the behaviour of the different nuclear domains. To follow DNA and RNA localization, we utilized osmium ammine and DNase-colloidal gold cytochemical reactions. The concentration of most DNA in the cap-shaped structures was demonstrated by these reactions. Confocal microscopy of cells processed by in situ nick-translation suggested that DNA was firstly cleaved and subsequently condensed in cup-shaped structures. Despite the strong nuclear modifications, nucleoli could be clearly recognized until the late apoptotic stages. PMID- 7868365 TI - Restricted occurrence of Locusta migratoria ovary maturing parsin in the brain corpora cardiaca complex of various insect species. AB - Ovary maturing parsin (OMP) is a gonadotrophic molecule previously isolated from the neurosecretory lobes of the corpora cardiaca of Locusta migratoria (acridian Orthoptera). A polyclonal antiserum directed against the two biologically active domains of the L. migratoria (Lom) OMP was used to investigate the occurrence of Lom OMP-like substances in brain-corpora cardiaca complexes of other insect species. Using immunohistochemistry, specimens of 40 different insect species belonging to 13 insect orders were tested. The Lom OMP-like substance was strictly limited to specimens of insect species belonging to the Acridae. It occurred in non-basophilic cells of the pars intercerebralis that project to the corpora cardiaca, as in Locusta. Although the antiserum only detected Lom OMP like material in the Acridae, it is possible that related molecules exist in other insects. The antiserum may be very specific for domains of the Lom OMP molecule that have not been highly conserved during evolution or possibly these domains are not accessible to the antiserum in other insects. PMID- 7868366 TI - Differential distribution of immunoreactive S-100 protein in mammalian testis. AB - The present study deals with the immunohistochemical localization of S-100 protein in the testes of seven mammalian species including rat, cat, dog, pig, sheep, cattle and horse. Significant differences are demonstrated in the cellular distribution and intensity of immunoreaction for the protein. In bull, ram, boar and cat testes S-100 protein was localized in the cytoplasm and nuclei of Sertoli cells. A particularly intense staining was seen in the modified Sertoli cells of the terminal tubular segment. With the exception of the cat and horse S-100 protein immunoreactivity was additionally found in epithelial cells of the straight testicular tubules and in the epithelial cells of the rete testis. Endothelial cells of capillaries, veins and lymphatic vessels are regularly S-100 immunoreactive in ruminants. Leydig cells were found to be strongly positive for S-100 protein in the cat and rat testes and to a lower degree in pig and horse testes. Finally a distinct immunostaining of peritubular cells was restricted to the testis of dogs and rats. The remarkable species-specific variations of immunoreactivity for S-100 protein in different cell types of the testis support the hypothesis that S-100 protein is multifunctional protein and may have a different function in testicular physiology. PMID- 7868367 TI - Lamellar bodies of rat alveolar type 2 cells have late endosomal marker proteins on their limiting membranes. AB - Alveolar type 2 cells are known to take up surfactant phospholipids and proteins from the alveolar space and recycle them into secretory organelles via a receptor mediated endocytic pathway. To clarify the intracellular route(s) through which materials ingested by the cells are processed, we examined the immunocytochemical localization of late endosomal and lysosomal membrane markers, rab 7 and lamp 1 proteins, within rat alveolar type 2 cells. The limiting membranes of lamellar bodies (LBs) showed positive immunoreactivity for both proteins, whereas multivesicular bodies (MVBs) exhibited positive immunoreactivity only for lamp 1 protein on free vesicles in the MVB lumen. From these findings, it is suggested that LBs are not only secretory granules, but also constitute one of the late endosomal compartments of the cells and that MVBs of this cell type may be targeted to cell organelle(s) other than lysosomes. PMID- 7868368 TI - Morphological, histochemical and stereological analysis of the female canine M. urethralis. AB - The M. urethralis was morphologically investigated in ten medium-sized female dogs of different breeds and age, as well as histochemically and stereologically analysed in a homogeneous group of five female beagles. Macroscopically, the muscle was essentially confined to the distal third and most strongly developed in the fourth quarter of the urethra. Here, it surrounded the urethra transversely at the ventral and lateral aspects, passing with its caudal fibres dorsally onto the vagina. The muscle fibres were assembled in groups of different sizes and usually separated by thick connective tissue septae. Based on the myofibrillar actomyosin ATPase (mATPase) reaction, type I and two main subtype II fibres could be differentiated. Type II fibres were, however, indistinguishable by their metabolic enzyme activities since both subclasses displayed oxidative glycolytic properties. The subtype II fibres containing the more acid-labile mATPase activity were classified as IIA, whereas the other main subtype was designated IIS (subtype) and considered as peculiar to the dog. In addition, the investigation revealed a rare fibre type exhibiting the histochemical profile of IIC fibres. There was no evidence of classical glycolytic IIB fibres. The M. urethralis was composed of 24% type I and 76% type II fibres with an average diameter of 34.9 and 28.5 microns, respectively. Connective tissue constituted 52.8% of the total muscle volume. Due to the predominance of fast twitch II fibres, the urethral muscle is not designed to maintain a high tone over long periods of time. Its primary role is to function rapidly and intermittently guaranteeing urinary continence during stress situations when other continence factors are overburdened. PMID- 7868369 TI - Redox processes in malaria and other parasitic diseases. Determination of intracellular glutathione. AB - The role of oxidative stress resulting from production of reactive oxygen species and/or from suppression of the cellular antioxidant capacity in parasitic infections is shortly reviewed. The experimental part of the paper deals with the glutathione (GSH)--glutathione reductase (GR) system, a cornerstone of intracellular antioxidant defence mechanisms. For studying this system in parasitic diseases such as malaria new or modified methods are required. Total glutathione comprising GSH and glutathione disulphide (GSSG) in blood samples was assayed as follows. One volume of blood (> or = 10 microliters) is mixed with two volumes of 5% sulphosalicylic acid; after centrifugation (5 min, 10000 g), 10 microliters of supernatant is taken for spectrophotometric analysis using the 5,5'-dithiobis(2-nitrobenzoate) (DTNB)-glutathione recycling assay. When compared with the original method, the procedure reported here is more sensitive, less time-consuming, avoids unfavourable pH-values and leads to a sample which when frozen is stable for months. In a pilot study, the method was applied to 14 patients suffering from malaria caused by Plasmodium falciparum. The concentrations of erythrocyte glutathione were significantly decreased in the patients (1.42 +/- 0.47 mM, mean +/- SD) when compared to age- and sex-matched controls (2.11 +/- 0.45 mM, P < 0.01). The findings are contrasted with P. falciparum cultures in vitro where glutathione levels are known to be elevated. Based on the characteristics of GR a concept of determining the redox state of single cells is introduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868370 TI - Production and characterization of monoclonal antibodies against the polyamine, spermine: immunocytochemical localization in rat tissues. AB - Two monoclonal antibodies of types IgG2b and IgG2a, anti-spermine-(Spm)-1 (ASPM 1) and anti-Spm-2 (ASPM-2) respectively were found among five clones of murine monoclonal antibodies, which were raised against Spm conjugated with bovine serum albumin via the cross-linker N-(gamma-maleimidobutyryloxy) succinimide (GMBS). Antibody specificity was evaluated by a recently developed ELISA binding test, and led to the study of tissue sections by immunocytochemistry (ICC). ASPM-1 showed exclusive immunoreactivity with Spm, with the exception of a negligible cross-reactivity (2.0%) with spermidine (Spd). ASPM-2, on the other hand, reacted almost equally with acetylspermine (Ac-Spm) and N1-acetylspermidine (N1-Ac-Spd) but with none of the other polyamine-related compounds tested. Complete agreement was obtained with the results of immunoblot analysis. Furthermore, results for antibody specificity obtained with the ELISA inhibition test and ICC model experiments using Sepharose gel beads strongly suggested that ASPM-1 recognizes the Spm molecule possessing at least a free terminal primary amino group, while ASPM-2 recognizes the Spm molecule acylated at both the terminal primary amino groups. An ICC method using ASPM-2 produced strong staining for polyamines (PAs) in the cytoplasm (but very few in the nuclei) of two different tumor cell lines and protein- or peptide-secreting cell systems, including exocrine and endocrine cell types; ASPM-1 showed immunoreactivity only with the tumor cell lines. These results strongly suggest that ASPM-2 may be useful for studies on actively proliferating and neoplastic cells, supporting our previously proposed idea that in immunocytochemistry PAs were converted to a variety of PA derivatives during the fixation process. PMID- 7868372 TI - The role of HLA molecules in the development of skin cancer. PMID- 7868371 TI - Relationship between cellular DNA synthesis, PCNA expression and sex steroid hormone receptor status in the developing mouse ovary, uterus and oviduct. AB - The proliferative activities of the different cellular compartments of the developing mouse ovary, uterus, and oviduct were studied by radioautographic assessment of DNA synthesis with [3H]-thymidine labeling and by immunohistochemical staining of proliferating cell nuclear antigen (PCNA). The distributions of estrogen and progesterone receptors (ER and PR) were studied by immunohistochemical staining. The values of the PCNA positive staining indices were a little higher than that of the radioautographic labeling indices. However, linear relations were shown for the two indices. The proliferative activities were high from postnatal day 1-7 and decreased from day 14 in the different cellular compartments of the ovary. The proliferative activities were high on days 1, 3 and decreased from day 7 in the uterus and oviduct. Staining of ER and PR was very weak in the surface epithelium, stroma and large follicles of the ovary. Positive staining for ER occurred from day 14 in the uterine epithelium and from day 7 in oviductal epithelium. Positive staining for PR was observed from day 1 in both the uterine and oviductal epithelium. However, the positivity of both ER and PR occurred from postnatal day 1 in the stromal cells of the uterus and oviduct. These results suggest that the appearance of the steroid receptors differ between the different cellular compartment of the reproductive organs. The proliferative activities have an inverse relation with the expression of the steroid hormone receptors in the female reproductive organs during developmental stages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868373 TI - Molecular analysis of the HLA-DRB genes in two tribes of Brazilian Indians. AB - The HLA-DRB1, -DRB3, -DRB4, and -DRB5 alleles of the Guarani and Kaingang Amerindians were characterized. Our previous serologic analyses detected three class II haplotypes among the Kaingang: DR2-DQ3, DR4-DQ3, and DR8-DQ4. In addition to these, the Guarani presented haplotype DR6-DQ3. Individuals typed serologically (67 Kaingang and 34 Guarani) were selected for molecular analyses. Using a set of 23 SSOs for hybridization of PCR products from generic DRB amplification six different haplotypes were identified, of which only three are shared by the two tribes. The oligonucleotide hybridization patterns are compatible, with haplotypes DRB1*1602-DRB5*02, DRB1*0404-DRB4*0101, DRB1*0802, and DRB1*0901-DRB4*0101 in the Kaingang tribe, and haplotypes DRB1*1602-DRB5*02, DRB1*0411-DRB4*0101, DRB1*1413-DRB3*0101, DRB1*0802, and DRB1*0901-DRB4*0101 among the Guarani. DRB1*1413 is a new allele, most closely related to DRB1*1402, which is common among South and North American Indians. At the segments analyzed, they differ solely at position 57, which is GAT (aspartic acid) in DRB1*1402 and AGC (serine) in DRB1*1413. This allele probably originated in South American Indians, resulting from a single segmental exchange event between alleles DRB1*1402 (the acceptor) and DRB1*0411. PMID- 7868374 TI - Acidic residues in the DR beta chain third hypervariable region are required for stimulation of a DR(alpha, beta 1*0402)-restricted T-cell clone. AB - We investigated the minimal requirements for stimulation of an antigen-specific HLA-DR(alpha, beta 1*0402)-restricted T-cell clone (Een217) by using transfectants expressing mutant DR beta chains as APCs. Antigen-specific stimulation of Een217 was induced with transfectants expressing DR(alpha, beta 1*0402) and DR(alpha, beta 1*0403) but not other DR4 subtypes that also bind the peptide recognized by this clone. Analysis of the effects of single amino acid substitutions in the beta chains of each of the DR4 subtypes revealed a requirement for acidic residues in the third HVR, particularly amino acid 71, in stimulation of clone Een217. Functional class II mutants were generated from nonstimulatory DR4 subtype beta chains by acidic residue substitutions within the third HVR. These data define the requirement for negatively charged residues in this region for peptide-induced stimulation of this T-cell clone. The required acidic residues can be located at either position 70, 71, or 74 in the DR beta chain. The negative charge in this segment of the DR beta chain alpha-helix may be required for direct interactions with the T-cell receptor of Een217 or may affect peptide conformation. PMID- 7868375 TI - Identification of a novel human T-cell receptor V beta subfamily by genomic cloning. AB - Although a large number of human TCRBV gene segment sequences have been reported, the extent of the germline repertoire is still not precisely known. Most TCRBV gene segments have been identified in cDNA clones. However, genes expressed on only a small number of peripheral T cells may be more easily detectable by analysis of genomic DNA. In the present study, screening of cosmid clones containing the BV24S1 gene segment revealed the presence of a novel TCRBV gene segment defining a new subfamily, BV25S1. The nucleotide sequence of the gene contained a single open reading frame and encoded structurally important amino acids at correct positions. Southern blot analysis indicated that the BV25 subfamily contained only this single member. A single nucleotide polymorphism was identified by nucleotide sequencing of the gene from multiple individuals. Amplification of rearranged BV25S1 genes from cDNA derived from PBLs confirmed that the BV25S1 gene segment was capable of normal rearrangement and transcription. PMID- 7868376 TI - Oligotyping of HLA-A2, -A3, and -B44 subtypes. Detection of subtype incompatibilities between patients and their serologically matched unrelated bone marrow donors. AB - We have set up a simple PCR-SSO oligotyping procedure that is able to discriminate ten HLA-A2 (2 PCR/11 probes), two HLA-A3 (1 PCR/1 probe), and two HLA-B44 subtypes (1 PCR/2 probes). The frequency of these subtypes has been determined in a large panel of local blood donors and leukemic patients in combination with their unrelated potential donors. A*0201 and A*0301 were the predominant subtypes (> 95%) for A2 and A3, respectively. B*4402 occurred twice as frequently as B*4403. A2 and B44 subtype mismatches were analyzed in a group of 30 patients and their 116 unrelated potential donors who were matched serologically (low-stringency matching: AB without splits, DR1-10). For seven patients (23%) at least one A2- or B44-subtype-mismatched donor was found. For two of these patients (7%), the subtype-mismatched donor would have been considered as compatible on the basis of high stringency matching (AB splits, DRB1 subtypes, DRB3/B5). For one patient of Mediterranean origin, all five donors recruited from a north European registry (matched with high stringency) appeared to be subtype incompatible (A*0201/A*0205). The rather low percentage of A2- and B4-subtype mismatches in DRB1/B3/B5 matched combinations confirms the significance of linkage disequilibria of HLA antigens. Because unrelated donor selection is done through international registries, however, class I subtyping might be necessary when individuals originate from different geographic areas. PMID- 7868377 TI - Differential regulation of mRNAs encoding protein kinase C isoenzymes in activated human B cells. AB - Stimulation of human B cells via HLA class II antigens leads to an increase of PKC activity as a consequence of a transcriptional upregulation of the PKC. Extending previous data, other known B-cell activators, which include anti-IgM, SAC, and TSST1, are shown here to increase the cytosolic PKC activity significantly. Human B cells express significant mRNA levels of the PKC alpha, beta, delta, epsilon, and zeta species while the gamma species is consistently absent. The levels of PKC alpha and epsilon mRNA are increased by exposure to a nonmitogenic anti-IgM antibody in a lymphoblastoid B-cell line while PKC beta and delta mRNA are instead downregulated by this agent. An anti-HLA class II antibody (D1.12) induced an increase of PKC alpha, beta, and delta mRNA. A time study of PKC mRNA levels in anti-IgM-treated cells showed that the accumulation of the PKC alpha mRNA precedes the increase of PKC enzymatic activity. Moreover, PKC beta mRNA decreased following treatment with SAC while, on the contrary, it increased following TPA, anti-HLA class II (1.35) mAb, or mitogenic anti-IgM treatment. Our results underline the complexity of signal transduction via the PKC pathway by revealing that the PKC isoforms are differentially regulated and are in keeping with the idea that they may have distinct physiologic roles in human B cells. PMID- 7868378 TI - Susceptible and protective major histocompatibility complex class II alleles in early-onset pauciarticular juvenile chronic arthritis. AB - Oligonucleotide typing for alleles of the MHC loci DRB1, DQA1, and DQB1 was performed in 160 patients suffering from EOPA, JCA (or JRA = juvenile rheumatoid arthritis). Allele and haplotype frequencies of the patients were compared with the data of an unrelated healthy control group consisting of 200 individuals. Analysis of frequencies shows that HLA alleles are associated not only with susceptibility to EOPA-JCA but also with protection from the disease. The presence of protection connected with certain HLA alleles was assessed using a calculation which takes into account the condition that if one allele is increased, all other alleles of the same locus must be decreased in compensation. Protection can be assumed only in cases where a given allele has an observed frequency which is significantly beyond the expected compensatory decrease. Thus a hierarchy of associations was observed in EOPA-JCA patients. The alleles of the haplotypes DRB1*11 (12)-DQA1*0501-DQB1*0301 as well as DRB1*08-DQA1*0401 DQB1*0402 were found to be associated with susceptibility to disease, whereas the alleles DRB1*07 and DQA1*0201 converge with significant protection from the disease. Whereas the association with disease susceptibility seems to depend on a sequence motif encoded in certain DQA1 alleles, protection is associated either with alleles of DRB1 or DQA1. PMID- 7868379 TI - Major histocompatibility complex class II haplotypes and linkage disequilibrium values observed in the CEPH families. PMID- 7868380 TI - 'Paying homage to the power of love'. Exceeding the bounds of professional practice. PMID- 7868381 TI - Scylla and Charybdis. Sexual abuse or 'false memory syndrome'? Therapy-induced 'memories' of sexual abuse. AB - The increasing importance and frequency of so-called 'false memories' of sexual abuse, which in reality never occurred, occasions a theoretical reflection about therapy-induced 'memories' of sexual abuse. Sexual abuse is first seen to involve a serious loss of psychic structure. As such it has much in common with other, endogenous forms of severe psychic disorders. Drawing upon the (Kleinian) categories of projective identification, projective counter-identification and psychotic personality aspects, together with the Jungian conception of the 'mutual unconsciousness' between therapist and patient, the author presents a psychodynamic hypothesis regarding the origins of 'false memories' or 'recovered memories' of sexual abuse. This is exemplified with two therapy cases involving such memories of abuse. PMID- 7868382 TI - Reality and mythology of child sexual abuse. PMID- 7868383 TI - The fear of analytic understanding. PMID- 7868384 TI - Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. I. Production, isolation and biological properties. AB - A series of new acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors termed terpendoles were isolated from the culture broth of a fungal strain FO-2546 which was proposed to belong to a new genus designated as Albophoma yamanashiensis. Among four structurally related terpendoles, terpendole C showed the most potent ACAT inhibitory activity with an IC50 value of 2.1 microM in an in vitro enzyme assay, followed by terpendoles D (IC50: 3.2 microM), A (15.1 microM) and B (26.8 microM). Evaluation of their ACAT inhibition in the cell assay using J774 macrophages indicated that terpendole D exhibited the highest specificity (cytotoxicity vs. ACAT inhibition) among microbial ACAT inhibitors we discovered so far. PMID- 7868385 TI - Gephyronic acid, a novel inhibitor of eukaryotic protein synthesis from Archangium gephyra (myxobacteria). Production, isolation, physico-chemical and biological properties, and mechanism of action. AB - A new antibiotic compound, gephyronic acid was isolated from the culture broth of the myxobacterium, Archangium gephyra strain Ar 3895. Up to 3 mg/liter was produced during the logarithmic and stationary growth phase. The compound is an aliphatic acid, which tends to form a hemiacetal. Both forms inhibited growth of yeasts and molds (MIC 1-25 micrograms/ml) and had a cytostatic effect on mammalian cell cultures (IC50 10-60 ng/ml). Gephyronic acid is a specific inhibitor of eukaryotic protein synthesis showing an IC50 of 1-2 x 10(-7) mol/liter in an in vitro translation assay. PMID- 7868386 TI - Disorazol A, an efficient inhibitor of eukaryotic organisms isolated from myxobacteria. AB - A new antibiotic, disorazol, was isolated from the culture broth of the myxobacterium, Sorangium cellulosum strain So ce 12. It is a macrocyclic compound containing two oxazole rings. The antibiotic acted against many fungi and mammalian cell cultures. The latter responded to extremely low doses (MIC 3-30 pg/ml). None of the tested bacteria and yeasts were inhibited. PMID- 7868387 TI - Darlucins A and B, new isocyanide antibiotics from Sphaerellopsis filum (Darluca filum). AB - Two new xanthocillin type antibiotics, darlucin A (1) and B (2), were isolated from fermentations of Sphaerellopsis filum (Darluca filum). Their structures were established by spectroscopic methods. The darlucins are the first known compounds with a 1,2-diisocyanoalkene moiety. Both compounds exhibited antibacterial, antifungal and weak cytotoxic activities. PMID- 7868388 TI - Isolation and structures of an antifungal antibiotic, fusarielin A, and related compounds produced by a Fusarium sp. AB - A new antifungal antibiotic, fusarielin A, and three related compounds, fusarielins B, C and D, were obtained from a culture of a Fusarium sp. The skeletal structure and the relative stereochemistry of fusarielin A were determined mainly on the basis of its NMR data, and the absolute structure was elucidated by using the exciton chirality method and the modified Mosher method. The structures of the other homologues were determined by comparison of their spectral data with those of fusarielin A. PMID- 7868389 TI - Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. II. Structure elucidation of terpendoles A, B, C and D. AB - Structures of terpendoles A, B, C and D, novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors, were determined by spectroscopic studies. All terpendoles consist of diterpene and indole moieties in common. Terpendoles A, C and D possess an additional isoprenyl unit via oxygen atom(s) of their diterpene moieties. The relative stereochemistries of terpendoles C and D were confirmed by NOE experiments and X-ray crystallographic analysis. PMID- 7868390 TI - Fudecalone, a new anticoccidial agent produced by Penicillium sp. FO-2030. AB - Penicillium sp. FO-2030, a soil isolate, was found to produce a new anticoccidial compound. The active compound, designated fudecalone, was isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and preparative HPLC. The structure of fudecalone was elucidated to be 3,3a,6,6a,7,8,9,10-octahydro-1-hydroxy-4,7,7-trimethyl-1H naphtho[1,8a- c]furan-6-one mainly by spectroscopic studies including various NMR measurements. The anticoccidial activity using cell systems indicated that schizont formation of monensin-resistant Eimeria tenella was completely inhibited by fudecalone at concentrations more than 16 microM. PMID- 7868391 TI - Production of 6,8a-seco-6,8a-deoxy derivatives of avermectins by a mutant strain of Streptomyces avermitilis. AB - Streptomyces avermitilis produces the anthelmintic and insecticidal secondary metabolite avermectins. Following mutagenesis of a recombinant strain, S. avermitilis K2038 (aveD X) with N-methyl-N'-nitro-N-nitrosoguanidine, a derivative strain K2057 (aveD aveE X), was isolated, which produced seven avermectin-related compounds different from the eight components of avermectins. Four among these seven compounds from mutant K2057 were found to be new metabolites. Their structures were 4'-deoleandrosyl-6,8a-seco-6,8a deoxyavermectin B1a, 4'-deoleandrosyl-6,8a-seco-6,8a-deoxy-5-oxoavermectin B1a, 4'-deoleandrosyl-6,8a-seco-6,8a-deoxy-5-oxoavermectin B2a and 6,8a-seco-6,8a deoxy-2,5-didehydroavermectin B2a, all of which lack the furan ring at C-6, C-8a. The mutation affecting the formation of the furan ring (aveE) is located in the center of the gene cluster for avermectin biosynthesis. PMID- 7868392 TI - Effect of polymyxin B nonapeptide on daptomycin permeability and cell surface properties in Pseudomonas aeruginosa, Escherichia coli, and Pasteurella multocida. AB - The present study was carried out to determine if sensitization of Gram-negative bacteria to the polyanionic antibiotic daptomycin by cationic molecules can be explained on the basis of decreased cell surface charge in order to better understand intrinsic resistance. Turbidimetric assessments of batch cultural growth kinetics revealed the outer membrane permeabilizer polymyxin B nonapeptide sensitized Pseudomonas aeruginosa and Escherichia coli to the hydrophobic probe novobiocin, whereas little or no sensitization was observed for two surface hydrophobicity variants of Pasteurella multocida. Polymyxin B nonapeptide and daptomycin synergistically inhibited growth of P. aeruginosa only. A hydrocarbon adherence assay revealed permeabilizing concentrations of polymyxin B nonapeptide increased cell surface hydrophobicity of P. aeruginosa and the hydrophobic P. multocida variant, while E. coli and the hydrophilic P. multocida variant remained unaffected. Measurement of cellular electrophoretic mobility showed polymyxin B nonapeptide permeabilization of P. aeruginosa to daptomycin occurred concomitantly with a significant decrease in cell surface charge, while no such sensitization occurred in organisms which failed to undergo polymyxin B nonapeptide-induced surface charge decreases. These data suggest that sensitization of Gram-negative bacteria to polyanionic lipopeptides by growth in the presence of polycationic outer membrane permeabilizers such as polymyxin B nonapeptide is dependent on diminution of overall cell surface charge and polarity, thereby allowing outer cell envelope permeation. PMID- 7868393 TI - Synthesis and biological activity of novel cephalosporins containing a (Z)-vinyl dimethylphosphonate group. AB - A series of cephalosporins containing a novel 7-[2-(Z)-(2-amino-thiazol-4- yl)-3 (dimethoxy-phosphoryl)-acryloylamino] group were prepared and their antibacterial activity measured against a range of pathogens. In general the compounds displayed a broad spectrum of activity against both Gram positive and Gram negative organisms, except Pseudomonas aeruginosa. Activity against the latter could be achieved by introducing a catechol moiety at the 3 position of the cephalosporin. The methyl phosphonates in general were stable to a wide range of beta-lactamases, including the TEM enzymes and the Enterobacter cloacae P99 chromosomal enzyme. In addition, they showed the advantage of being highly water soluble. PMID- 7868394 TI - Arohynapene D, a new anticoccidial agent produced by Penicillium sp. FO-2295. PMID- 7868395 TI - Structure of patulodin, a new azaphilone epoxide, produced by Penicillium urticae. PMID- 7868396 TI - Total synthesis and inhibitory activity against gelatinase B of YL-01869P. PMID- 7868397 TI - The effect of 1 beta-methyl substituent and the basicity in C-2 side chain in carbapenem antibiotics on the activity against Pseudomonas aeruginosa oprD2 and nalB mutants. PMID- 7868398 TI - Production of a new methylated 6,8a-seco-6,8a-deoxy derivative of the avermectins by a transformant strain of Streptomyces avermitilis. PMID- 7868399 TI - Direct production of 5-oxo derivatives of avermectins by a recombinant strain of Streptomyces avermitilis. PMID- 7868400 TI - Bacterial multidrug resistance--emphasis on efflux mechanisms and Pseudomonas aeruginosa. PMID- 7868401 TI - High level kanamycin resistance associated with the hyperproduction of AAC(3)II and a generalised reduction in the accumulation of aminoglycosides in Acinetobacter spp. AB - The clinical isolate of Acinetobacter baumannii strain SAK contains an actively transcribed aacC2 gene and a latent aadB gene that encode the aminoglycoside modifying enzymes, AAC(3)II and AAD(2"), respectively. In an attempt to activate the aadB gene, the strain was cultured in the presence of kanamycin which is a substrate for AAD(2"). Although it was possible to isolate kanamycin resistant derivatives these were not associated with detectable AAD(2") activity. Instead, there was a marked increase in the level of AAC(3)II activity which was associated with amplification of the aacC2 gene. PMID- 7868402 TI - Interaction of divalent cations, quinolones and bacteria. AB - The interaction between divalent cations and quinolones and the mechanism by which the former antagonizes the antimicrobial activities of the latter were investigated. In the presence of either magnesium or calcium chloride, the MICs of 18 quinolones for Gram-positive and Gram-negative bacteria increased. Accumulation of and inhibition of DNA synthesis by quinolones were decreased in the presence of magnesium chloride while, in the presence of EDTA, there was no increase in the concentration of accumulated quinolone for any of the agents tested. Only with nalidixic acid was there enhancement of the inhibition of DNA synthesis. Chelation of selected quinolones by magnesium was demonstrated with a fluorescence assay which showed that the extent to which fluorescence (consistent with chelation) was enhanced varied with the quinolone. Assessment of the strength of the magnesium-quinolone complexes with the chelating agent EDTA demonstrated that some of the complexes could be broken. Thin layer chromatography of quinolones and quinolone-magnesium complexes provided evidence that the components of the complex were probably combined in a ratio of 1:1 and that reduced intracellular accumulation of the quinolones in the presence of magnesium was unlikely to be due to a complex being too bulky to be taken through the porin channels. In contrast with permeabilizers which are known to utilize the self-promoted uptake pathway, none of the quinolones studied permeabilized Gram-negative bacteria to lysozyme, caused enhanced fluorescence to 1-N-phenyl naphthylamine (NPN) or increased the leakage of periplasmic beta-lactamase into the culture medium. The reduced activities of the quinolones in the presence of divalent cations may be the result of the chelation of exogenous ions and, possibly, lipopolysaccharide- or lipoteichoic acid-associated magnesium ions, thereby resulting in less drug being available to enter the bacterium. Alternatively, reduced activity may be due to a fundamental effect on the interaction between quinolones and their target DNA gyrase. PMID- 7868403 TI - Farm animals as a putative reservoir for vancomycin-resistant enterococcal infection in man. AB - Using a highly selective enrichment broth, 62 isolates of vancomycin-resistant Enterococcus faecium were obtained from non-human sources; 35 isolates from raw sewage, 22 from farm animals and 5 from uncooked chickens. All strains possessed the Van A gene, conferring high-level resistance to vancomycin (MIC > or = 256 mg/L). Ribotyping of 42 of these isolates resulted in 14 distinguishable patterns. Two ribotyping patterns were found among isolates from animals and sewage and those from clinical sources. A blood and a urine isolate from separate hospital patients and porcine isolates shared the same ribotyping pattern number 6 and a stool isolate from a patient in the community and sewage isolates shared another pattern, number 10. This finding suggests that animals may serve as a reservoir of vancomycin-resistant enterococci (VRE), which may enter the human food chain. The emergence of VRE in hospital patients may reflect selection of these organisms in the hospital environment by antibiotic usage from which nosocomial spread might occur. PMID- 7868404 TI - Faecal carriage and nosocomial spread of vancomycin-resistant Enterococcus faecium. AB - Eight clinical isolates of vancomycin-resistant Enterococcus faecium (VRE) were obtained from four renal and four other in-patients within an 11 week period during 1992. Characterisation of the isolates by restriction enzyme analysis with Sal I and rRNA gene restriction patterns (ribotyping) showed them to be clonally related. During the next 3 months an additional 14 VRE were isolated from hospital patients, nine of which were indistinguishable by ribotyping from the strain associated with the outbreak. An epidemiological survey was instigated in order to determine the level of carriage of this VRE. A total of 354 stool specimens was screened using a highly selective enrichment broth. VRE were detected in the stools of 11/73 (15%) of renal patients, 5/97 (5%) of other hospital patients and 3/184 (2%) of patients based in the community. Of the 25 stool isolates that were further characterised by ribotyping, 17 were indistinguishable from the outbreak strain. The remaining eight isolates gave seven different patterns. Patients harbouring the outbreak strain stayed in hospital significantly longer and had received more antibiotic treatment, for longer, than those patients from whom other VRE had been isolated. There was no significant difference in vancomycin or cephalosporin usage between the two groups of patients. Ribotyping showed there to be a number of clones of VRE carried by patients and that one of these clones was especially prevalent and has been responsible for the outbreak of infection in the renal unit. The technique also showed the presence of different VRE in general practice patients suggesting they are not just a hospital phenomenon. PMID- 7868405 TI - Microbiological surveillance during selective decontamination of the digestive tract (SDD) AB - The use of selective decontamination of the digestive tract (SDD) as prophylaxis against nosocomial respiratory tract infection remains controversial, largely because of concerns that, in the long term, it may promote the emergence of antibiotic-resistant strains. This report describes the results of surveillance cultures and susceptibility testing undertaken during the course of a 2-year, double-blind study of the efficacy of SDD which was conducted in a respiratory intensive care unit (ICU). Surveillance specimens from the alimentary tract and trachea were obtained from each patient on admission and then twice weekly until 48 h after discharge from the unit. Specimens were cultured semiquantitatively and organisms from morphologically distinct colonies were identified by standard methods; the susceptibilities of these isolates were determined by the disc diffusion method. Five thousand, nine hundred and sixty surveillance samples from 239 patients were processed in this way. Compared with the placebo group, SDD caused a significant reduction in the incidence of colonization of the alimentary tract with aerobic Gram-negative bacilli (AGNB), and Candida spp. were almost totally eliminated. The incidence of colonization with enterococci increased in both groups, while the incidence of both colonization of the alimentary tract with strains of coagulase-negative staphylococci and methicillin-resistant Staphylococcus aureus and infection caused by these organisms increased in the SDD group. Acinetobacter spp. were the most common bacteria associated with unit acquired colonization and lower respiratory tract infection in both groups. The acquisition of strains of Pseudomonas aeruginosa and cefotaxime- and/or tobramycin-resistant Enterobacteriaceae was significantly greater in the placebo group than in the SDD group, although tobramycin-resistant strains of Proteus, Morganella and Providencia spp. were isolated from three of 114 patients receiving SDD. The use of SDD did not lead to an overall increase in antibiotic resistance amongst the AGNB usually associated with ICU-acquired infection. However, colonization with strains which were either resistant to one or more of the antibiotic components of the regimen or which were not inhibited by the regimen was observed and may subsequently lead to infection. PMID- 7868406 TI - Effect of rufloxacin upon non-specific immune defences: in-vitro, ex-vivo and in vivo results. AB - This study investigated in-vitro, ex-vivo and in-vivo the immunomodulatory effects of rufloxacin. 0.5 MIC of rufloxacin significantly enhanced human macrophage phagocytosis and increased intracellular killing of Klebsiella pneumoniae in vitro. Pre-incubation of K. pneumoniae with rufloxacin made the bacteria more susceptible to both phagocytosis and intracellular killing by human macrophages than control organisms. Following pre-exposure of macrophages to 0.5 MIC of rufloxacin, there was a significant increase in the intracellular killing of K. pneumoniae compared with the controls, indicating the ability of rufloxacin to cross biological membranes and to remain active within phagocytes. Ex-vivo experiments show that iv administration of rufloxacin in mice lead to an increase in both phagocytic and microbicidal intracellular activity by phagocytes. In-vivo models of experimental infections showed that prophylactic administration of rufloxacin increased the survival of mice after challenge with Candida albicans. PMID- 7868407 TI - Inhibition of the renal excretion of tazobactam by piperacillin. AB - A 1:4 by weight of combination of tazobactam, a new beta-lactamase inhibitor, and piperacillin, is now under development in Japan. After bolus iv administration of the combination to beagle dogs, piperacillin both significantly raised the area under plasma concentration time curve (AUC0 approximately infinity) and significantly decreased the total body clearance (Cltot) of tazobactam. The percentage binding of tazobactam and piperacillin to dog and human serum protein was the same for the combination as for the individual compounds. Piperacillin significantly decreased the renal clearance (Clr) and the clearance ratio (Cr) of tazobactam in dogs. Further, probenecid significantly decreased Clr of both tazobactam and piperacillin, and the Cr of tazobactam and piperacillin approximately reached unity. These results indicate that piperacillin inhibits the renal excretion of tazobactam. Both tazobactam and piperacillin are secreted by a tubular anion transport system which is identical to the probenecid secretion system. PMID- 7868408 TI - Piperacillin/tazobactam compared with ticarcillin/clavulanate in community acquired bacterial lower respiratory tract infection. AB - The efficacy and safety of a new combination parenteral antibiotic, piperacillin/tazobactam, was compared with that of parenteral ticarcillin/clavulanate in the treatment of adult patients with community acquired lower respiratory tract infections. A total of 299 patients were enrolled in this multicentre, double-blind, comparative study; 177 received piperacillin/tazobactam and 122 received ticarcillin/clavulanate. Of these, 119 met the evaluability criteria (69, piperacillin/tazobactam and 50, ticarcillin/clavulanate). The study drugs (piperacillin/tazobactam 3 g/375 mg or ticarcillin/clavulanate 3 g/100 mg) were given every 6 h by slow iv infusion for a minimum of 5 days. The favourable clinical response (cured and improved) rates of evaluable patients were 84% and 64% at endpoint (P < 0.01) for piperacillin/tazobactam and ticarcillin/clavulanate, respectively. The favourable bacteriological response at the early follow-up (eradicated and presumed eradicated) were 91% and 67% for piperacillin/tazobactam and ticarcillin/clavulanate, respectively (P < 0.01). At endpoint, 84% and 64%, respectively (P = 0.02) had a favourable response. The most common adverse experiences involved the gastrointestinal tract and occurred in 31.6% of the piperacillin/tazobactam group compared with 20.5% in the ticarcillin/clavulanate group (P = 0.02). These events were mild and generally did not affect therapy. Piperacillin/tazobactam appears to be more effective than ticarcillin/clavulanate in this patient population and is generally well tolerated. PMID- 7868409 TI - In-vitro activity of clinafloxacin (CI-960) and PD 131628-2 against anaerobic bacteria. AB - The antimicrobial activities of two new quinolones, CI-960 and PD 131628-2 were determined against 339 strains of anaerobic bacteria and compared to cefoxitin, imipenem and metronidazole. The NCCLS-approved Wadsworth agar dilution technique with Brucella-lysed blood agar was used throughout the study. Breakpoints of the new quinolones are 2 mg/L, and breakpoints for cefoxitin, imipenem and metronidazole are 32, 8 and 16 mg/L, respectively. CI-960 displayed excellent activity, inhibiting all strains tested at 1 mg/L. PD 131628-2 inhibited 94% of Bacteroides fragilis, 75% of other B. fragilis group isolates, 87% of Prevotella spp, 79% of the Fusobacterium mortiferum-varium group, 74% of non-sporing gram positive bacilli, and 89-100% of Clostridium spp other than Clostridium difficile at 2 mg/L. None of the eight strains of C. difficile was inhibited at 2 mg/L although they were inhibited at 4 mg/L. PD 131628-2 inhibited all strains of other Bacteroides spp, Porphyromonas spp, and Fusobacterium nucleatum at < or = 1 mg/L. PMID- 7868410 TI - Penicillin susceptibility testing of penicillinase producing Neisseria gonorrhoeae by the E test: a need for caution. AB - The penicillin MICs of 52 clinical isolates of penicillinase producing Neisseria gonorrhoeae (PPNG) and five reference strains were tested by agar dilution and the E test. All 52 PPNG were scored resistant (> or = 2 mg/L) by agar dilution whereas only 78.8% (41/52) and 82.7% (43/52) were classified as resistant by normal (0.016-256 mg/L) and low range (0.002-32 mg/L) E test MICs respectively. Isolates with an E test penicillin MIC > or = 0.19 mg/L should be checked by a specific test for beta-lactamase production. PMID- 7868411 TI - The utility of the PCR method to study aacA gene heterogeneity in Serratia marcescens. PMID- 7868412 TI - Effect of medium pH on the activity of dirithromycin and erythromycylamine in Bactec broth against Mycobacterium avium complex. PMID- 7868413 TI - False resistance to metronidazole of anaerobic bacteria using the E test. PMID- 7868414 TI - Concentrations of rifabutin in plasma and cerebrospinal fluid in cynomolgus monkeys. PMID- 7868415 TI - Penetration of fluconazole into abscess fluid. PMID- 7868416 TI - Toxicity of clarithromycin in the treatment of Mycobacterium avium complex infection in a patient with AIDS. PMID- 7868417 TI - Inferences on passive diaphragm mechanics from gross anatomy. AB - The diaphragm is a relatively thin curved structure that is categorized in mechanics as a membrane. Tension in the membrane is given by the product of muscle thickness and stress parallel to the fiber bundles. If all muscle fibers were cylindrical and extended from origin to insertion, the ratio of thickness near the chest wall (CW) to thickness near the central tendon (CT) would vary inversely with the ratio of CW to CT perimeters. In freshly excised diaphragms of 36 mongrel dogs, the ratios of the perimeters (CT/CW) in the right and left costal diaphragm were 0.63 +/- 0.04 and 0.62 +/- 0.04, respectively. The means of the ratio of thickness near CW to that near CT in the right and left costal regions were 0.96 +/- 0.07 and 0.95 +/- 0.05, respectively, consistent with a nearly constant relationship between costal diaphragm membrane tension and muscle stress in the direction of the fibers. In the crural diaphragm, the average ratio of the perimeters of the insertions on CT to CW was 1.16 +/- 0.10. The average ratio of thickness of crural CW to CT was 1.25 +/- 0.11. The discrepancy between the perimeter ratio and thickness ratio in the costal diaphragm is incompatible with the muscle consisting of uniform fibers extending from CW to CT. Our data suggest that muscle fibers are either in series with a smaller number along the smaller perimeter or that they terminate by tapering within the muscle bundle. Both arrangements are consistent with previous anatomic studies (Gordon et al. J. Morphol. 201: 131-143, 1989). Having a nonuniform number of fibers mechanically in series is compatible with uniform stress in the fibers if the membrane is sufficiently curved as in a domed structure. PMID- 7868419 TI - Apnea after normocapnic mechanical ventilation during NREM sleep. AB - We determined whether normocapnic mechanical ventilation at high tidal volume (VT) and breathing frequency (f) during non-rapid-eye-movement (NREM) sleep would cause apnea. Seven normal sleeping subjects were placed on assist-control mechanical ventilation (i.e., subject initiates inspiration) and VT was gradually increased to 2.1 times eupneic VT (1.17 +/- 0.04 liters). This high VT was maintained for 5 min, the ventilator mode was switched to controlled mechanical ventilation, and f was increased gradually from 9.5 +/- 1.0 (during assist control mechanical ventilation) to 14.0 +/- 0.7 breaths/min. Normocapnia (end tidal PCO2 = 44 +/- 1.2 Torr) was maintained throughout the trials. Inspiratory effort was completely inhibited during the period of sustained high VT and f, and apnea occurred immediately after cessation of the passive mechanical ventilation. The duration of the apnea preceding the first inspiratory effort was 20.3 +/- 2.3 s or 7.1 times the eupneic expiratory duration and 5 times the expiratory duration chosen by the subject during assist-control mechanical ventilation. We conclude that inhibition of inspiratory motor output occurs during and after normocapnic mechanical ventilation at high VT and f during NREM sleep. These neuromechanical inhibitory effects may serve to initiate and prolong apnea. PMID- 7868418 TI - Streptococcus pneumoniae-induced pulmonary hypertension and systemic hypotension in anesthetized sheep. AB - Because some patients with Streptococcus pneumoniae bacteremia may present with shock, we reasoned that this organism may produce substances that cause shock. To test this hypothesis, type III pneumococcus supernatant, suspended in 10 ml of sterile water, was infused over 1 min in 8 adult anesthetized sheep. Normal saline was used as a control and had no effect on any of the hemodynamic parameters. Infusion of supernatant resulted in a precipitous fall in cardiac output from a control value of 4.25 +/- 0.54 to 2.80 +/- 0.43 (SE) l/min, a fall in mean systemic arterial pressure from 70 +/- 4 to 49 +/- 8 mmHg, and an increase in the mean pulmonary arterial pressure from 13 +/- 2 to 23 +/- 4 mmHg within 1 min after the infusion was completed. The peak hemodynamic effects were observed at approximately 3 min and returned to normal within 10 min after the infusion was completed. The thromboxane B2 level increased from a control value of 10 +/- 5 to 156 +/- 43 pg/ml at 3 min after the infusion was completed and decreased to 63 +/- 34 pg/ml at 20 min. A second identical dose of pneumococcal supernatant, repeated within 2 h of the first dose, had no effect on hemodynamic variables. Pretreatment with indomethacin, 5 mg/kg body wt, completely blocked the hemodynamic effects of pneumococcal supernatant (n = 3 sheep). Thus, we conclude that S. pneumoniae supernatant contains substances that cause septic shock syndrome through the synthesis of arachidonic acid metabolites and that a sublethal dose of the supernatant causes rapid tachyphylaxis. PMID- 7868420 TI - Oxygen sensors in vascular smooth muscle. AB - Inhibition or activation of cellular function due to acute decreases in PO2 can be considered in terms of two different processes: 1) a sensor that monitors PO2 decreases and 2) transduction systems directed from the O2 sensor to reactions that control cellular function. We used the norepinephrine-contracted aortic smooth muscle model to study the nature of the O2 sensor and transduction system during decreased PO2-evoked relaxations. The phosphorylation potential, a measurement of kinetic energy required for ATP hydrolysis, was decreased to 30% of control at the onset of relaxation and progressively fell as muscle relaxed. The free inorganic phosphate intracellular concentration ([Pi]) was experimentally increased approximately 0.6 mM during transients that followed a rapid decrease in PO2. Relaxations to 80% of maximal force were more rapid under conditions of an augmented [Pi] than in control rings, and they occurred at a higher phosphocreatine concentration and phosphocreatine-to-free creatine ratio but at the same phosphorylation potential. Results support the operation of a cytochrome aa3 O2 sensor in the mechanism of decreased PO2-evoked relaxations and implicate an increase in [Pi] and a decrease in kinetic energy in the transduction mechanism directed at rate-limiting reactions that control force. PMID- 7868421 TI - Continuous measurements of changes in pulmonary capillary surface area with 201Tl infusions. AB - The impact of physiological and pathological processes on metabolism and transport of a variety of substances traversing the pulmonary vasculature depends in part on the capillary surface area available for exchange, and a reliable method for detecting changes in this parameter is needed. In this study, a continuous-infusion approach was used to investigate the response of the pulmonary capillary surface area to increases in flow and left atrial pressure. Isolated rat lungs were perfused with an acellular perfusion solution containing 125I-labeled albumin (an intravascular indicator) and 201Tl, a K+ analogue which is concentrated within lung cells. The extraction of 201Tl from the perfusate was 61% greater at low flow (8.5 ml/min) than at high flow (26 ml/min), and rapid changes in extraction were observed when flow was altered. In contrast, the permeability-surface area product was 76% greater when lungs were perfused at high flow than at low flow, suggesting comparable increases in pulmonary capillary surface area in these zone 2 lungs (airway pressure = 5 cmH2O, left atrial pressure < 0 cmH2O). In a second group of experiments, increases in left atrial pressure to 14 cmH2O (zone 3 lungs) at a constant flow of 8.5 ml/min increased the permeability-surface area product by only 18% despite increases in average intravascular pressure that were at least as high as those associated with high perfusion rates. 201Tl infusions provide a useful method for detecting and quantifying changes in pulmonary capillary surface area. PMID- 7868422 TI - Electrically evoked myoelectric signals in back muscles: effect of side dominance. AB - This work had two goals, to study the effect of hand dominance on myoelectric signal variables and fatigue indexes in back muscles and to assess the repeatability of the estimates of such variables. Myoelectric manifestations of muscle fatigue were studied in the right and left longissimus dorsi muscles of five right-handed and five left-handed normal male subjects. Myoelectric signals (M waves), evoked by stimulation applied to a muscle's motor point, were detected with surface electrodes. Each test consisted of eliciting a tetanic contraction of 30 s duration with supramaximal stimulation at 25 Hz and was repeated five times on 5 different days for each subject. The mean and median frequencies of the resulting power spectra of the M waves were plotted vs. time, and fatigue indexes were obtained from the time course of these variables. Only two-thirds of the elicited contractions provided signals of sufficiently good quality to obtain reliable estimates of the mean and median frequencies. Criteria for acceptability are described. Analysis of variance and paired comparisons showed a statistically significant effect of side dominance on fatigue indexes in the right-handed subjects but not in the left-handed subjects. Normalized initial slope and other fatigue indexes based on spectral variables demonstrated myoelectric manifestations of fatigue that were greater on the dominant side. We surmise that the differences are related to the fiber type modifications associated with the unilateral usage of the upper limbs and the consequent activation of the nondominant side of the back. PMID- 7868423 TI - Decreasing stimulation frequency-dependent length-force characteristics of rat muscle. AB - Effects of decreasing stimulation frequency on length-force characteristics were determined for rat medial gastrocnemius muscle. The peripheral nerve was stimulated supramaximally with a succession of twitch and frequencies of 100, 50, 40, 30, and 15 Hz. Active peak tetanic and twitch forces and active muscle geometry were analyzed. Optimal muscle length and active slack length shifted significantly (P < 0.05) to higher muscle length by a maximum of 2.8 and 3.2 mm, respectively. Further significant effects were found for distal fiber length and mean sarcomere length of distal fiber (increases) and for fiber angle and aponeurosis length (decreases). Neither muscle length range between active slack and optimal length nor aponeurosis angle was altered significantly. We concluded that decreasing stimulation frequency-dependent length-force characteristics are affected by a complex interaction of length-dependent calcium sensitivity, potentiation of the contractile system, distribution of sarcomere length, and interactions between force exerted and aponeurosis length. Length-dependent calcium sensitivity seems to be a major factor determining the magnitude of the shift of optimal muscle length. PMID- 7868424 TI - Age-related differences in diaphragm muscle injury after lengthening activations. AB - The susceptibility of postnatal day 15 and adult rat diaphragms (DIAs) to acute injury after repetitive isovelocity lengthening activations was examined in vitro. Forces were measured during two phases of each stimulation protocol: 1) isometric phase: during the first 300 ms of each 500-ms train, DIA length was not changed; and 2) isovelocity lengthening phase: during the remaining 200 ms of each stimulus train, DIA was lengthened at a constant velocity from 90 to 110% of optimal length. At maximal activation (75 Hz and a lengthening velocity of 1.0 optimal length per second), the maximum force measured during the isometric phase and that measured during the isovelocity lengthening phase were both greater in adult DIAs than in day 15 DIAs but both declined to a greater extent in adults with repetitive activation. Ultrastructural analysis showed that after lengthening activations muscle fiber injury was very evident in adult but much less prevalent in day 15 DIAs. This difference in susceptibility between the adult and day 15 DIAs did not depend on differences in peak force or absolute velocity of lengthening. We conclude that lengthening activations result in DIA injury and that the adult is more susceptible than its younger counterpart. PMID- 7868425 TI - Aortic baroreflex control of heart rate after 15 days of simulated microgravity exposure. AB - To determine the effects of simulated microgravity on aortic baroreflex control of heart rate, we exposed seven male subjects (mean age 38 +/- 3 yr) to 15 days of bed rest in the 6 degrees head-down position. The sensitivity of the aortic cardiac baroreflex was determined during a steady-state phenylephrine-induced increase in mean arterial pressure combined with lower body negative pressure to counteract central venous pressure increases and neck pressure to offset the increased carotid sinus transmural pressure. The aortic-cardiac baroreflex gain was assessed by determining the ratio of the change in heart rate to the change in mean arterial pressure between baseline conditions and aortic baroreceptor isolated conditions (i.e., phenylephrine + lower body negative pressure + neck pressure stage). Fifteen days of head-down tilt increased the gain of the aortic cardiac baroreflex (from 0.45 +/- 0.07 to 0.84 +/- 0.18 beats.min-1.mmHg-1; P = 0.03). Reductions in blood volume and/or maximal aerobic capacity may represent the underlying mechanism(s) responsible for increased aortic baroreflex responsiveness after exposure to a ground-based analogue of microgravity. PMID- 7868426 TI - Acute pulmonary response to intravenous histamine using forced oscillations through alveolar capsules in dogs. AB - We measured the time course of alveolar input impedance using two alveolar capsule oscillators after intravenous bolus administration of 20 mg of histamine in open-chest dogs. Impedances (24-200 Hz) were obtained every 2 s after an injection for 100 s. Each impedance was fit with a model consisting of a pathway (with resistance and inertance) leading from the alveolar capsule into a subpleural region (with elastance EA) that, in turn, was connected to the lung compartment (consisting of the remainder of the lung and positive end expiratory pressure system) via another pathway (with resistance RA). In all cases (6 dogs, 2 capsules each), the resistance and inertance leading from the alveolar capsules were negligible. The correlation of the relative increases in RA obtained from the two capsule oscillators in each dog was not significant. The correlation for EA also was not significant. The times at which RA achieved values of 20% greater than baseline were not significantly correlated between the two capsules, as was the case for EA. However, the baseline values of EA and RA from a given capsule were significantly correlated, as were their fractional increases with histamine. These results show that both the magnitude and timing of changes in local lung resistance and elastance are spatially extremely heterogeneous. PMID- 7868427 TI - Modulation of bronchial smooth muscle function in horses with heaves. AB - Four mechanisms that modulate airway smooth muscle function in normal horses were studied in the bronchi of horses affected by the airway obstructive disease heaves. Results were compared with data from historical controls studied by the same personnel in the same laboratory. Rings from the left cranial lobar bronchus (LB1) and small bronchi (5 mm OD) were suspended in muscle baths, and the isometric tension were measured. The inhibitory nonadrenergic noncholinergic (iNANC) function was studied in LB1. After the LB1 segments were pretreated with atropine and contracted with histamine, electrical field stimulation (EFS) induced little or no relaxation, indicating iNANC dysfunction in horses with heaves. Bronchi from animals with heaves were hyporesponsive to EFS and acetylcholine. Epithelial removal augmented the contractile response of small bronchi to acetylcholine more in animals with heaves than in control animals, indicating an enhanced function of epithelial-derived relaxing factor. In contrast, cyclooxygenase inhibition with meclofenamate (10(-6) M) increased the EFS-induced contraction of small bronchi less in affected horses than in control horses, suggesting a change in prostaglandin production in favor of excitatory prostanoids. We conclude that in the bronchi of horses with heaves; the iNANC function is defective, the response of smooth muscle to cholinergic activation is diminished, the production of epithelial-derived relaxing factor is enhanced, and the inhibitory function of prostanoids is reduced. PMID- 7868428 TI - Failure of hemoconcentration during standing to reveal plasma volume decline induced in the erect posture. AB - The hypothesis was tested that the hemoconcentration observed during standing provides erroneous information about the induced plasma volume (PV) decline. Male volunteers (n = 10) stood quietly for 15 min after supine rest. On standing arterial hemoglobin (Hb) rose slowly to reach an increase of 5.9 +/- 0.3% (SE) after 15 min. Early after resuming the supine position, Hb increased further to 9.2 +/- 0.5% above control level and then declined gradually. Venous antecubital blood from the left arm supported horizontally at heart level in both the supine and standing positions (no hydrostatic load) showed very similar changes. However, Hb in venous blood collected during standing from the right arm held in the natural dependent position rose much more markedly than that in arterial blood and in venous blood from the horizontal arm (470 +/- 122, 105 +/- 24, and 55 +/- 7% greater increase at 5, 10, and 15 min, respectively). Taken together, these observations indicated that 1) analyses of arterial blood sampled from the standing subject grossly underestimated the prevailing "overall" hemoconcentration and PV decline, a phenomenon ascribed to incomplete mixing of blood between dependent and nondependent regions; 2) arterial blood sampled from the recumbent subject early (60 s) after completion of standing reflected the "true" overall intravascular hemoconcentration, with a calculated PV decline of no less than 511 +/- 27 ml, because the supine position facilitated proper mixing of blood between circulatory compartments; 3) data from common venous sampling from the dependent arm during standing primarily reflected a regional hemoconcentration (fluid loss) in the arm rather than PV decline; and 4) short term quiet standing caused a more prominent and hemodynamically important decrease in PV than usually believed. PMID- 7868429 TI - Sex differences in surface EMG interference pattern power spectrum. AB - Sex differences in the spectral parameters of the surface electromyogram (EMG) power spectrum were studied during voluntary muscle contractions of different strength with rest in between. The influence of two different types of leads (unipolar and bipolar) on the values of the spectral parameters was also investigated under the same experimental conditions. The subjects were 15 healthy female and 15 healthy male volunteers. The relationship between the amplitude (root mean square) of the EMG and the force developed was not linear. The mean values of the median power frequency were lower in women than in men. With both types of lead, the increase in force was accompanied by a progressive increase in median power frequency in male and female subjects. The significant differences in spectral parameters observed in the two sexes are probably correlated with anatomic differences. PMID- 7868430 TI - Changes in potential controllers of human skeletal muscle respiration during incremental calf exercise. AB - The purpose of this study was to evaluate the consequences of non-linear changes in phosphocreatine (PCr) and pH during incremental calf exercise on estimates of ADP and cytosolic free energy of ATP hydrolysis (delta GATP). Six subjects performed incremental plantar flexion exercise on a treadle ergometer while muscle P(i) metabolism (PCr, P(i), ATP) and pH were followed using 31P-nuclear magnetic resonance spectroscopy. Changes in ADP and delta GATP were estimated with the assumption that there was equilibrium of the creatine kinase reaction and homogeneous tissue metabolite pools. All six subjects showed a threshold for onset of cellular acidosis that occurred on average at 47.3 +/- 12.7% of peak work rate (PWR). In five of the six subjects, PCr and P(i) showed accelerated rates of change above the threshold for onset of cellular acidosis. In all six subjects, ADP, when correctly calculated considering changes in pH, rose in a curvilinear fashion that was well described by a Michaelis-Menten hyperbola through 60-100% of PWR, with a mean apparent Michaelis-Menten constant of 43.1 +/ 17.1 microM ADP and a predicted maximal oxidative rate at PCr = 0, which was 241 +/- 94% of PWR. delta GATP rose linearly with work rate from -62.9 +/- 1.8 kJ/mol during unloaded treadling to -55.0 +/- 1.8 kJ/mol at PWR. If we assume a linear O2 uptake-to-work rate relationship, these results are most consistent with control of respiration being exerted through delta GATP under these conditions (incremental exercise by human calf muscle).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868431 TI - Exercise-induced oxidative stress: glutathione supplementation and deficiency. AB - Glutathione (GSH) plays a central role in coordinating the synergism between different lipid- and aqueous-phase antioxidants. We documented 1) how exogenous GSH and N-acetylcysteine (NAC) may affect exhaustive exercise-induced changes in tissue GSH status, lipid peroxides [thiobarbituric acid-reactive substances (TBARS)], and endurance and 2) the relative role of endogenous GSH in the circumvention of exercise-induced oxidative stress by using GSH-deficient [L buthionine-(S,R)-sulfoximine (BSO)-treated] rats. Intraperitoneal injection of GSH remarkably increased plasma GSH; exogenous GSH per se was an ineffective delivery agent of GSH to tissues. Repeated administration of GSH (1 time/day for 3 days) increased blood and kidney total GSH [TGSH; GSH+oxidized GSH (GSSG)]. Neither GSH nor NAC influenced endurance to exhaustion. NAC decreased exercise induced GSH oxidation in the lung and blood. BSO decreased TGSH pools in the liver, lung, blood, and plasma by approximately 50% and in skeletal muscle and heart by 80-90%. Compared with control, resting GSH-deficient rats had lower GSSG in the liver, red gastrocnemius muscle, heart, and blood; similar GSSG/TGSH ratios in the liver, heart, lung, blood, and plasma; higher GSSG/TGSH ratios in the skeletal muscle; and more TBARS in skeletal muscle, heart, and plasma. In contrast to control, exhaustive exercise of GSH-deficient rats did not decrease TGSH in the liver, muscle, or heart or increase TGSH of plasma; GSSG of muscle, blood, or plasma; or TBARS of plasma or muscle. GSH-deficient rats had approximately 50% reduced endurance, which suggests a critical role of endogenous GSH in the circumvention of exercise-induced oxidative stress and as a determinant of exercise performance. PMID- 7868432 TI - Metabolic characteristics of primary inspiratory and expiratory muscles in the dog. AB - These experiments examined the metabolic properties of the canine respiratory muscles. Because the costal diaphragm (COD), crural diaphragm (CRD), parasternal intercostals (PI), triangularis sterni (TS), and transversus abdominis (TA) are active during quite breathing in the dog, we hypothesized that these muscles would have different metabolic profiles (i.e., higher oxidative and antioxidant enzyme activities) compared with ventilatory muscles recruited only at increased ventilatory requirements [e.g., scalene (SC) and external oblique (EO)] and locomotor muscles [e.g., deltoid (DEL)]. To test this hypothesis, muscle samples were removed from six healthy adult dogs and analyzed to determine the activities of citrate synthase (CS), phosphofructokinase (PFK), 3-hydroxyacyl-CoA dehydrogenase (HADH), and superoxide dismutase (SOD). The activities of these enzymes were interpreted as relative measures of metabolic capacities, and enzyme activity ratios were considered as representing relationships between different metabolic pathways. Analysis revealed that CS and HADH activities were significantly higher (P < 0.05) in the PI, COD, CRD, and TS compared with those in all other muscles. Muscles with the lowest CS, HADH, and SOD activities (i.e., SC, TA, EO, DEL) generally had the highest PFK activities, Furthermore, the PFK/CS ratio was significantly lower in the PI, COD, CRD, and TS compared with that in all other muscles studied. These data support the notion that the canine PI, COD, CRD, and TS are metabolically different from other key ventilatory muscles. PMID- 7868433 TI - Skeletal muscle pH assessed by biochemical and 31P-MRS methods during exercise and recovery in men. AB - The present study was designed to compare evaluation of skeletal muscle metabolism (vastus lateralis) evaluated by 31P-magnetic resonance spectroscopy (MRS) and biochemical analysis. During identical isometric knee extensor exercise protocols to fatigue in eight men, biopsy samples were taken at rest, peak exercise, and 32 s postexercise and 31P-MRS data were collected continuously for phosphocreatine (PCr), pH, ATP, and P(i) at 8- or 32-s intervals. There was no difference in ATP or pH measurements between the two techniques at rest, during peak exercise, or in recovery. Corresponding measurements of pH by the two techniques were closely related (r = 0.88, P < 0.01), and pH measured by 31P-MRS was closely related to muscle lactate accumulation (r = -0.84, P < 0.001). The level of PCr at peak exercise, expressed as a percentage of the baseline value, was not different between the two techniques (42 +/- 15 vs. 46 +/- 15%). The results indicate that, in skeletal muscle in normal subjects, 1) measurements of pH and PCr at rest and during exercise do not differ between the 31P-MRS and biopsy techniques and 2) muscle pH measured by 31P-MRS is closely related to lactate accumulation in men. Our data suggest that direct comparison of results of studies of exercise metabolism using these two techniques is warranted. PMID- 7868434 TI - Adverse effect of hyperinflation on parasternal intercostals. AB - The force-generating ability of the parasternal intercostals is maintained during acute hyperinflation in the dog (Jiang et al. Am. Rev. Respir. Dis. 139: 522-528, 1989). In the present studies, we assessed whether the ability of these muscles to expand the rib cage and inflate the lungs is really maintained. We thus measured the electromyogram and the changes in length of these muscles, the axial motion of the sternum and the ribs, and the changes in pleural pressure and tidal volume in anesthetized vagotomized phrenicotomized dogs during selective parasternal stimulation and during spontaneous breathing at different lung volumes corresponding to 0, 5, 10, and 15 cmH2O positive airway pressure. Compared with functional residual capacity, parasternal stimulation at 15 cmH2O positive airway pressure caused a mild decrease in muscle shortening, a large reduction in cranial rib motion, and a large reduction in pleural pressure fall. The caudal displacement of the sternum, however, was increased. Similar alterations in rib and sternal motions and in muscle shortening were seen during spontaneous breathing; tidal volume was markedly reduced as well. These observations thus indicate that hyperinflation affects the action of the parasternal intercostals on the rib cage; their rib-elevating action is decreased, whereas their action on the sternum is increased. As a result, their ability to inflate the lung is reduced. Thus, the inflationary actions of both the diaphragm and parasternal intercostals are reduced by hyperinflation. PMID- 7868435 TI - Effects of acute and chronic maternal exercise on fetal heart rate. AB - Maternal-fetal effects of cycle ergometer conditioning (heart rate of 145 beats/min at 25 min/day for 3 days/wk) were studied during the second and third pregnancy trimesters. Subjects were 22 previously sedentary women and 16 nonexercising pregnant control women. Fetal heart rate (FHR) characteristics were studied before, during, and after 15 min of upright cycling at a maternal heart rate target of 145 beats/min at the end of both the second and third trimesters. Despite higher cycling power outputs in the exercised group, mean FHR responses were similar in both groups and conformed to 1) gradual increase in FHR baseline during exercise, 2) normal variability, and 3) normal reactivity. Fetal bradycardia was observed during (n = 1) and after (n = 2) exercise in three isolated tests. The timing of these events suggested that the likelihood of significant fetal hypoxia is highest in the immediate postexercise period. These results also support the hypothesis that physically conditioned women can perform at higher exercise power outputs than sedentary women without inducing fetal hypoxic stress. Further study is recommended to examine possible fetal and placental adaptations to maternal aerobic conditioning. PMID- 7868436 TI - Effect of exercise on cold tolerance and metabolic heat production in adult and aged C57BL/6J mice. AB - Two groups of adult (12-mo-old) and two groups of aged (24-mo-old) C57BL/6J male mice were subjected to a standardized cold stress test (3-h partial restraint at 6 degrees C). One group from each age group was tested in the morning, and the other was tested in the afternoon. Half of the mice were subjected to running exercise on a treadmill during 1 h before the cold stress test. The other half were placed on a nonoperational treadmill for 1 h before the cold stress test. One hour of exercise resulted in improvement of cold tolerance during the subsequent cold exposure in both age groups but only during afternoon testing. Improvement in cold tolerance was not accompanied by an elevation of cold-induced metabolic heat production in adult mice. Metabolic heat production in aged mice showed only modest elevation. The discrepancy between improvement in cold tolerance and lack of elevation of metabolic heat production suggests that the primary mechanism for augmentation of cold tolerance after exercise in the afternoon is an improvement in cold-induced vasoconstriction of skin vessels, which is probably normally compromised in the afternoon. PMID- 7868438 TI - Hypoxic and hypercapnic ventilatory responses in Prader-Willi syndrome. AB - Abnormalities of ventilatory control may play a significant role in the pathophysiology of sleep-disordered breathing in patients with the Prader-Willi syndrome (PWS). We measured rebreathing hypercapnic and hypoxic ventilatory responses (HCVR and HPVR, respectively) during wakefulness in 8 nonobese PWS (NOB PWS) and 9 obese PWS (OB-PWS) patients and compared their results with those from 24 healthy nonobese control (NOB-CON) and 10 obese control (OB-CON) subjects. The slope of HCVR was similar in NOB-PWS patients and NOB-CON subjects (NS). However, HCVR was significantly lower in OB-PWS patients than in OB-CON subjects (P < 0.02). In PWS patients, the mean point of origin of the positive slope of HCVR occurred at a significantly higher end-tidal PCO2 than in either control group. During isocapnic hypoxic challenges, six PWS patients had no significant HPVR. In the remainder, mean slopes of HPVR were -0.80 +/- 0.06 l.min-1.%arterial O2 saturation-1 in five NOB-PWS patients and -0.68 +/- 0.15 l.min-1.%arterial O2 saturation-1 in six OB-PWS patients. These responses were significantly decreased compared with those in the control groups (P < 0.006). We conclude that NOB-PWS patients have normal HCVR, which is blunted in OB-PWS patients. Furthermore, isocapnic HPVR is either absent or markedly reduced in PWS patients. The severity of abnormality of the HPVR is independent of the degree of obesity. We postulate that the primary abnormality of ventilatory control in PWS affects peripheral chemoreceptor pathways. PMID- 7868439 TI - Absent peripheral chemosensitivity in Prader-Willi syndrome. AB - Abnormalities in ventilatory control during wakefulness and sleep have been observed in patients with Prader-Willi syndrome (PWS). The role of peripheral chemoreceptors in the pathophysiology of abnormal ventilatory responses in PWS is unknown. We studied peripheral chemoreceptor function during wakefulness in 17 genetically confirmed PWS patients [age 27.0 +/- 2.5 (SE) yr; 7 males, 10 females; body mass index 31.1 +/- 1.4 kg/m2] and compared their responses with 17 control subjects matched for age, sex, and body mass index. All PWS and control subjects had normal resting end-tidal PCO2 and arterial O2 saturation while awake. Peripheral chemoreceptor function was assessed by the ventilatory responses to 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 15% CO2 in O2. Control subjects decreased minute ventilation (VE) by 15.5 +/- 3.6% during hyperoxia. However, PWS patients increased VE by 17.6 +/- 3.3%, indicating a paradoxical response to hyperoxia (P < 0.00001). After CO2 vital capacity breaths, PWS patients showed no significant change and control subjects showed a marked increase (P < 0.0001) in VE. During N2 breathing, again PWS patients showed no change and control subjects exhibited a marked increase (P < 0.00005) in VE. We conclude that PWS patients have absent peripheral chemoreceptor ventilatory responses. We speculate that the lack of ventilatory responses is due to primary peripheral chemoreceptor dysfunction and/or defective afferent pathways to central controllers. PMID- 7868437 TI - Vitamin E does not prevent exercise-induced increase in pulmonary clearance. AB - It has been observed that sustained exercise results in a prolonged increase in alveolar epithelial permeability, as assessed by the pulmonary clearance rate of aerosolized 99mTc-labeled diethylenetriaminepentaacetate (Lorino et al. J. Appl. Physiol. 67: 2055-2059, 1989). The involvement of lipid peroxidation in this increased permeability was tested in seven nonsmoking volunteers by comparing the exercise-induced increases in pulmonary 99mTc-diethylenetriaminepentaacetate clearance before and after a 3-wk supplementation with oral vitamin E (1,000 IU/day), according to a protocol designed as a single-blind crossover study. The 60-min exercise was performed on a treadmill at a constant load corresponding to 80% of maximal O2 uptake. Administration of vitamin E, a very important antioxidant, did not reduce the exercise-induced increase in lung clearance, suggesting that the exercise-induced increase in lung epithelial permeability does not primarily result from the occurrence of lipid peroxidation in the alveolar membrane. This result thus corroborates the hypothesis of an alteration of the intercellular tight junctions due to the mechanical effects of hyperventilation. PMID- 7868440 TI - Respiratory muscle pressure analysis in pressure-support ventilation. AB - The extent to which respiratory muscles are exerted during partially supported ventilation is difficult to differentiate, because these muscles and the ventilator work simultaneously to produce ventilation. We have developed a new method for determining the pressure developed by the respiratory muscles in partially supported ventilation. In seven patients on pressure-support ventilation (PSV), pressure, flow, and lung volume change were measured at the airway opening. Various PSV levels (0-15 cmH2O) were applied to each patient in random order. By utilizing a model of respiratory mechanics, we calculated the pressure developed by the respiratory muscles and the inspiratory work performed by the muscles from the measured parameters by use of the resistance and elastance of the respiratory system obtained during controlled ventilation. Increasing PSV from 0 to 15 cmH2O modulated the resultant breathing pattern, i.e., increasing tidal volume and decreasing respiratory rate. The respiratory muscle pressure, although less negative, had a shape that corresponded to the shape of airway occlusion pressure at each PSV level, and both pressures decreased concomitantly with increasing PSV. The respiratory muscle work progressively decreased with increasing PSV. This analysis enabled clear and continuous quantifications of the respiratory muscle force generation and inspiratory work during partially supported ventilation. PMID- 7868441 TI - Diaphragmatic pressure-flow relationship during hemorrhagic shock: role of nitric oxide. AB - In the vascularly isolated resting and contracting (3 Hz) canine hemidiaphragm, we studied the effect of intra-arterial infusion of the nitric oxide (NO) inhibitor NG-nitro-L-arginine (LNA) on the relationship between phrenic arterial perfusion pressure (Pphr) and blood flow (Qphr). In separate groups of animals, either saline or LNA (final concn 6 x 10(-4) M) was infused into the phrenic artery over 20 min. The diaphragm was then autoperfused by diverting flow from the left femoral artery. Arterial blood pressure was reduced in stages by controlled hemorrhage. The Pphr-to-Qphr relationship was plotted for each animal, and the third-order polynomial of best fit was determined by least squares regression. The inflection point of this relationship was determined for each animal. In the contracting and resting diaphragms, the inflection point corresponded to Pphr values of 83.6 +/- 4.7 and 72.5 +/- 6.8 mmHg, respectively, in the saline-treated group compared with 86.2 +/- 2.7 and 76.8 +/- 5.1 mmHg, respectively, in the LNA-treated group. In the contracting diaphragm, LNA reduced Qphr uniformly across the entire range of perfusion pressures. In the resting diaphragm, the effect of LNA was not uniform. At perfusion pressures below the inflection point, the flow was reduced in proportion to the reduction in inflection point flow. At higher perfusion pressures, Qphr was decreased to a greater extent than could be accounted for by the change in inflection point flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868442 TI - Histochemical and mechanical properties of diaphragm muscle in morbidly obese Zucker rats. AB - The purpose of the present study was to evaluate the effects of chronic mass loading produced by obesity on the structural and functional characteristics of the diaphragm in lean and obese Zucker rats. The trapezius muscle served as an internal control. The studies were carried out on 17 lean (303 +/- 24 g) and 16 obese (698 +/- 79 g) Zucker rats. We observed that the diaphragms from obese animals were restructured such that the overall contribution of type I and IIa fibers was significantly increased. As a consequence of this remodeling, overall diaphragm thickness was selectively greater in obese animals. In small isolated diaphragm bundles studied in vitro, we also detected a reduction in specific force in obese animals that was not detected in the trapezius muscle. In vitro fatigue resistance, assessed by repeated stimulation, was similar in muscles of lean and obese animals. Diaphragm fiber oxidative capacity (succinate dehydrogenase activity) was also comparable in lean and obese animals. We conclude that in obesity the diaphragm undergoes modest remodeling that may be beneficial in enhancing force generation. PMID- 7868443 TI - Pulmonary interstitial pressure in anesthetized paralyzed newborn rabbits. AB - In anesthetized paralyzed term newborn rabbits at various postgestational ages (from birth up to 16 days), we measured by micropuncture technique the hydraulic pressure of the pulmonary interstitium (Pip), the extrapleural parietal interstitium, and the pleural liquid. Birth data refer to cesarian-delivered nonbreathing rabbits. Pip increased from 0.5 +/- 2 to 6 +/- 0.7 cmH2O from birth up to 2 h and then decreased, becoming subatmospheric at 5 h and attaining -6 +/- 1.6 cmH2O at 16 days. Over the same period of time, pressure in the extrapleural parietal interstitium and the pleural liquid remained fairly constant at an average value of approximately -1.5 and -2 cmH2O, respectively. The wet-to-dry weight ratio of the lungs decreased from 7.8 +/- 0.4 to 4.9 +/- 0.1 at 16 days. Plasma protein concentration was 4.2 +/- 0.4 g/dl at birth, decreased to 3.2 +/- 0.5 g/dl at 1 h from delivery, and increased back to 4 +/- 0.6 g/dl at 16 days. Pleural liquid protein concentration was 3 +/- 0.1 g/dl at birth and decreased to 1.2 +/- 0.2 g/dl at 16 days. In the first hours of postnatal life, the marked increase in Pip appears to be a key factor in favoring fluid clearance from pulmonary interstitium into the pulmonary capillaries and the pleural space. This factor vanishes after approximately 6 h because of the marked decrease in Pip. PMID- 7868444 TI - Effects of altered muscle activation on oxidative enzyme activity in rat alpha motoneurons. AB - Some controversy exists as to whether alpha-motoneurons adapt their oxidative metabolism to changes in chronic activity levels and to altered status of their end organs, as occurs in other neuron types in the central nervous system. We measured, using a personal computer-based image analysis system, succinate dehydrogenase (SDH) activity in rat hindlimb motoneurons under conditions of increased activity (daily voluntary exercise plus treadmill endurance training, the latter 2 h/day, 4 days/wk, for 12 wk) and in a condition of muscle disuse (tetrodotoxin-induced paralysis for 2 wk) in which muscle oxidative enzymes are reduced. Although exercise-trained medial gastrocnemius showed significant adaptations (increased mean SDH activity of type I and increased proportion and total SDH activity of type I and combined I + IIa fibers), SDH activity of innervating motoneurons (identified by retrograde tracing using fast blue) was unchanged. In addition, tetrodotoxin-induced disuse, which results in hindlimb atrophy and SDH decreases (30% decrease measured in medial gastrocnemius muscle homogenates), failed to alter soma SDH or size in unspecified lumbar motoneurons. These results, obtained over a wider range of activity levels than in previous reports, suggest that the oxidative enzymes of motoneurons do not change despite clear adaptations in the muscles they innervate. PMID- 7868445 TI - Ventilatory output and acetylcholine: perturbations in release and muscarinic receptor activation. AB - Cholinergic transmission may be part of the normal neurochemical processes that support spontaneous ventilation. If this is true, perturbations in acetylcholine (ACh) turnover should alter ventilatory output in a predictable manner. With the use of the isolated perfused brain stem-spinal axis from the neonatal rat, the effects of modifiers of ACh release and blockers of muscarinic receptors on spontaneous C4 (phrenic) output were determined. Vesamicol and cetiedil, inhibitors of ACh release, caused depression and cessation of the C4 output in a dose-dependent manner when added to the perfusate. Muscarinic blockers, particularly M1 and M3 blockers, caused a similar depression. 4-Aminopyridine and tetraethylammonium chloride, facilitators of ACh release, caused stimulation of C4 (phrenic) output. The depressive effects of the blockers and inhibitors were reversible with facilitation of ACh release except in the case of cetiedil. These findings are consistent with the view that the synaptic turnover of endogenous ACh is an important part of the normal neurochemical process that supports and modulates ventilation. PMID- 7868446 TI - Respiratory muscle activity during sleep-induced periodic breathing in the elderly. AB - During spontaneous sleep-induced periodic breathing in elderly subjects, we have found that tidal volume oscillations are related to reciprocal oscillations in upper airway resistance. The purpose of this study was to address the mechanism of the relationship between oscillations in tidal volume and upper airway resistance in elderly subjects with sleep-induced periodic breathing. We hypothesized that the spontaneous periodic breathing observed in non-rapid-eye movement (NREM) sleep in elderly subjects would be closely related to fluctuations in upper airway resistance and not to changes in central motor drive to ventilatory pump muscles. Therefore, in eight healthy elderly subjects, we measured costal margin chest wall peak moving time average electrical inspiratory activity (CW EMG), ventilation variables, and upper airway resistance during sleep. Five of eight subjects had significant sine wave oscillations in upper airway resistance and tidal volume. For these five subjects, there was a reciprocal exponential relationship between peak upper airway inspiratory resistance and tidal volume or minute ventilation [r = -0.60 +/- 0.20 (SD) (P < 0.05) and -0.55 +/- 0.26 (P < 0.05), respectively], such that as resistance increased, ventilation decreased. The relationship between CW EMG and tidal volume or minute ventilation was quite low (r = 0.12 +/- 0.32 and -0.07 +/- 0.27, respectively). This study demonstrated that oscillations in ventilation during NREM sleep in elderly subjects were significantly related to fluctuations in upper airway resistance but were not related to changes in chest wall muscle electrical activity. Therefore, changes in upper airway caliber likely contribute to oscillations in ventilation seen during sleep-induced periodic breathing in the elderly. PMID- 7868447 TI - Systemic hemorrhage augments local O2 extraction in canine intestine. AB - When O2 delivery (QO2) to a tissue is reduced, microvascular adjustments facilitate increases in O2 extraction, thereby delaying the onset of O2 supply limited metabolism until a critically low QO2 is reached. The present study investigated the contribution of the autonomic nervous system to these adjustments by measuring O2 extraction in isolated intestine. In anesthetized dogs, a 30- to 50-g segment of intestine was vascularly isolated and its QO2 was decreased in stages by reducing the speed of an occlusive pump. In a normovolemic group (n = 11), blood volume was maintained to minimize sympathetic tone while flow to the intestine was reduced. In a hypovolemic group (n = 7), blood volume was removed in stages to augment sympathetic tone as flow to the intestinal segment was simultaneously reduced. A hypovolemic alpha-adrenergic-blocked (alpha blocked) group (n = 6) was identical to the corresponding alpha-adrenergic intact (alpha-intact) group except that alpha-adrenergic effects were inhibited with phenoxybenzamine (3 mg/kg). The systemic critical O2 extraction ratio in the alpha-blocked group (69 +/- 6%) was less than that in the alpha-intact group (77 +/- 7%; P = 0.05). In the intestine, the critical O2 extraction ratio was significantly poorer in the normovolemic (45 +/- 11%) group than in either hypovolemic group (alpha-intact: 69 +/- 3%, P < 0.00005; alpha-blocked: 62 +/- 9%, P < 0.005). These findings demonstrate that systemic hemorrhage significantly augments critical O2 extraction in intestine during progressive local stagnant hypoxia and suggest that nonadrenergic vasoconstrictor mechanisms may play an important role. PMID- 7868448 TI - Running-induced muscle injury and myocellular enzyme release in rats. AB - The relationships and time course of exercise-induced muscle damage, estimated by beta-glucuronidase activity and microscopy, to muscle swelling, estimated by muscle water content and microscopy, and to the serum activity of creatine kinase (CK) and the concentration of carbonic anhydrase III were studied in rats 2, 12, 48, and 96 h after 90 min of intermittent running uphill (+13.5 degrees) or downhill (-13.5 degrees) at a speed of 17 m/min. The injury was more pronounced in soleus after uphill running and in the red parts of quadriceps femoris and in the white part of vastus lateralis after downhill running, whereas triceps brachii was not damaged. Increase in muscle water content preceded the increase of beta-glucuronidase activity. Both running protocols similarly increased serum CK 2 h postexercise. After downhill running a second peak in serum CK was observed 48 h later. The CK changes were not in concert with the changes in muscle water content or beta-glucuronidase activity, suggesting that these responses may not be mechanistically (or causally) related. PMID- 7868449 TI - Effects of maximal exercise and venous occlusion on fibrinolytic activity in physically active and inactive men. AB - The purposes of this study were to 1) characterize changes in fibrinolytic activity in response to maximal exercise and 5-min venous occlusion and 2) compare responses in men of various habitual physical activity levels. Tissue plasminogen activator (TPA) activity and plasminogen activator inhibitor 1 (PAI 1) activity were measured in 15 inactive, 15 regularly active, and 15 highly active men. Data were analyzed using a three-way analysis of variance with repeated measures. Pretest TPA activity was similar among groups. TPA activity increased postexercise with higher values seen in the active groups (P < 0.001). The highly active group also significantly increased TPA activity postvenous occlusion (P < 0.01). Pretest PAI-1 activity was different among groups, with the inactive group showing the highest activity and the highly active group the lowest (P < 0.05). PAI-1 activity decreased with exercise (P < 0.01) but did not change with venous occlusion. In conclusion, active men exhibited greater changes in fibrinolytic activity with maximal exercise and venous occlusion than inactive men. This enhanced fibrinolytic activity may be an important mechanism mediating the cardioprotective effect provided by regular physical activity. PMID- 7868450 TI - Longitudinal development of young talented speed skaters: physiological and anthropometric aspects. AB - A longitudinal analysis of a group of speed skaters was done to identify the performance-determining factors for a successful speed skating career. This paper presents both the physiological and anthropometric results of this longitudinal study. Twenty-four athletes from the Dutch National Junior Speed Skating Team were followed from age 16-17 yr to age 20-21 yr. During the development from junior to senior speed skater, a number of anthropometric and physiological variables changed. There were no differences between successful and unsuccessful speed skaters from an anthropometric perspective; consequently, it was not possible to distinguish successful from unsuccessful athletes on anthropometric grounds. The longitudinal data showed that at a younger age the successful speed skaters had similar oxygen consumption, mechanical efficiency, and power output values compared with the unsuccessful speed skaters. Later in the study, successful speed skaters distinguished themselves by the ability to produce higher power output values. There were no anthropometric or physiological relationships found in this study on which performance at the age of 20-21 yr could be predicted with measurements at a junior age. PMID- 7868451 TI - Blood lactate and acid-base balance in graded neonatal hypoxia: evidence for oxygen-restricted metabolism. AB - This study examines the neonatal response to graded hypoxia and determines the arterial PO2 (PaO2) threshold for oxygen-restricted metabolism as confirmed by the development of lactic acidosis and altered oxygen handling. Anesthetized, intubated, and ventilated 3-day-old pigs (n = 56) were randomly assigned to one of five predetermined acute (120 min) graded hypoxia groups: normoxia (PaO2 = 80 Torr) or mild (60 Torr), moderate (40 Torr), moderately severe (30 Torr), or severe (20 Torr) hypoxia. In moderate hypoxia, lactate and acid-base homeostasis were unaltered due to a significant increase in oxygen extraction (P < 0.05) that was sufficient to maintain the arteriovenous oxygen content difference (oxygen uptake). In moderately severe hypoxia, increased arterial lactate and decreased HCO3- and base excess were evidence of anaerobic metabolism, yet pH was unaltered, indicating adequate buffering. In this group, despite the increase in oxygen extraction, oxygen uptake was reduced, indicating the onset of oxygen restricted metabolism. The severe hypoxia group had significantly increased lactate (21.7 +/- 3.9 mmol/l), decreased pH (7.01 +/- 0.07) and base excess ( 21.5 +/- 3.0 mmol/l), and depletion of HCO3- (9.7 +/- 1.6 mmol/l) (P < 0.0001). Here, increases in oxygen extraction were severely limited by availability, resulting in significantly reduced oxygen uptake, anaerobic metabolism, and profound lactic acidosis. PMID- 7868453 TI - Effect of muscular exercise on chronic relapsing experimental autoimmune encephalomyelitis. AB - We examined whether physical exercise affected the development of an autoimmune response, experimental autoimmune encephalomyelitis (EAE), which is a demyelinating disease leading to paralysis. EAE was inducted on day 0, in rats of both sexes, by injecting them with spinal cord tissue in adjuvant. From days 1 to 10 after injection, exercised rats (n = 55) ran on a treadmill (60-120 min/day) before the onset of the paralytic disease. Clinical signs of the disease (ataxia, paralysis, and body mass loss) were examined in exercised and control rats (n = 54). Three types of EAE were induced: monophasic, acute, and chronic relapsing (CR)-EAE (3 bouts of disease, CR-EAE 1, 2, and 3, separated by remissions). Exercise significantly delayed the onset of CR-EAE 1 (P = 0.001) and the 1st day of maximum severity of CR-EAE 1 (P = 0.001) and CR-EAE 2 (P = 0.002). Moreover, the duration of CR-EAE 1 was significantly decreased in exercised rats compared with control rats (P = 0.004). The peak severity of the different types of EAE was not modified by exercise. The present study indicates that endurance exercise during the phase of induction of EAE diminished lightly only one type of EAE (CR EAE) and therefore did not exacerbate the autoimmune disease. PMID- 7868452 TI - Airway surface liquid thickness as a function of lung volume in small airways of the guinea pig. AB - The average thickness and distribution of airway surface liquid (ASL) on the luminal surface of peripheral airways were measured in normal guinea pig lungs frozen at functional residual capacity (FRC) and total lung capacity (TLC). Tissue blocks containing cross sections of airways of internal perimeter 0.188 3.342 mm were cut from frozen lungs and imaged by low-temperature scanning electron microscopy (LTSEM). Measurements made from LTSEM images were found to be independent of freezing rate by comparison of measurements at rapid and slow freezing rates. At both lung volumes, the ASL was not uniformly distributed in either the circumferential or longitudinal direction; there were regions of ASL where its thickness was < 0.1 micron, whereas in other regions ASL collected in pools. Discernible liquid on the surfaces of airways frozen at FRC followed the contours of epithelial cells and collected in pockets formed by neighboring cells, a geometry consistent with a low value of surface tension at the air liquid interface. At TLC airway liquid collected to cover epithelial cells and to form a liquid meniscus, a geometry consistent with a higher value of surface tension. The average ASL thickness (h) was approximately proportional to the square root of airway internal perimeter, regardless of lung volume. For airways of internal perimeter 250 and 1,800 microns, h was 0.9 and 1.8 microns at FRC and 1.7 and 3.7 microns at TLC, respectively. For a given airway internal perimeter, h was 1.99 times thicker at TLC than at FRC; the difference was statistically significant (P < 0.01; 95% confidence interval 1.29-3.08).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868454 TI - Stroma-free hemoglobin increases blood pressure and GFR in the hypotensive rat: role of nitric oxide. AB - The short-term systemic and renal hemodynamic effects of two stroma-free hemoglobin (SFH) solutions, one unmodified and the other modified by cross linking, were examined in anesthetized rats after hemorrhagic hypotension. Both forms of SFH increased mean arterial pressure (MAP) and glomerular filtration rate (GFR) to baseline (prehemorrhage) values. The increase in MAP induced by unmodified SFH was greater than the increase in MAP caused by an albumin solution isoncotic to the unmodified SFH solution. Similarly, the increase in MAP caused by the modified SFH was also substantially greater than that induced by an albumin solution of comparable oncotic pressure to the modified SFH solution. Both unmodified and modified SFH increased GFR. As with MAP, the increase in GFR induced by both SFH solutions was greater than that associated with the oncotically matched albumin solutions. In separate experiments, the effects of nitric oxide (NO) inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) on MAP after hemorrhagic hypotension and subsequent infusion of unmodified SFH or albumin were also examined. In the albumin-infused rats, L-NAME increased MAP. In marked contrast, NO inhibition with L-NAME had no further effect on MAP when infused after SFH. We conclude that both unmodified and modified SFH solutions acutely improve MAP and GFR by the combined effects of intravascular volume expansion resulting from the colloid effect of the protein and by inactivation of NO. PMID- 7868455 TI - Effect of hyperbaric oxygen on tissue distribution of mononuclear cell subsets in the rat. AB - In a previous study we found a significant temporary decrease in the ratio of CD4/CD8 (helper, inducer/suppressor, cytotoxic) T lymphocytes in the peripheral blood of healthy human volunteers after exposure to a single commonly used profile of hyperbaric oxygen (HBO). The transient nature of the changes suggested redistribution of T-cell subsets. The purpose of the present study was to verify such a redistribution and to locate possible target organs in an animal model. A single exposure of rats to HBO (0.28 MPa) induced a highly significant rapid decrease in the CD4/CD8 ratio in peripheral blood count (P < 0.0001), confirming our previous findings in humans. HBO also induced a significant increase in the CD4/CD8 ratio in the lungs and lymph nodes (P < 0.001) and a significant decrease in the ratio in the spleen (P < 0.01). Furthermore, exposure to HBO induced a significant increase in T cells bearing surface interleukin-2 receptors in the blood, spleen, lungs, and lymph glands (P < 0.001) and a significant decrease in T cells expressing alpha beta-receptors in the lungs (P < 0.001) and lymph glands (P < 0.05). Our findings suggest rapid T-cell activation after a brief exposure to HBO, with shifts of CD4 and CD8 subsets and variations in T-cell receptor type. These rapid changes in the parameters of cell-mediated immunity may represent the activation of protective mechanisms against the toxic effect of oxygen or the early stages of pulmonary oxygen toxicity. PMID- 7868456 TI - Sympathetic and blood pressure responses to voluntary apnea are augmented by hypoxemia. AB - Oscillations of arterial pressure during sleep are the hemodynamic hallmark of the sleep apnea syndrome. The mechanism of these transient pressure elevations is incompletely understood. To investigate the role of the arterial chemoreflex in the neurocirculatory responses to apnea, we measured mean arterial pressure (MAP; Finapres) and muscle sympathetic nerve activity (MSNA; peroneal microneurography) during voluntary end-expiratory apnea during exposure to room air, 10.5% O2 in N2 (hypoxemia), and 100% O2 (hyperoxia) in 11 healthy men. While the men breathed spontaneously, MSNA (in bursts/min) rose during hypoxemia and decreased during hyperoxia and MAP remained unchanged. During room air exposure, apnea led to a rise of 94 +/- 54% in MSNA total amplitude and a rise of 6.5 +/- 2.1 mmHg in MAP. MSNA and MAP increased by 616 +/- 158% and 10.8 +/- 2.4 mmHg, respectively, during hypoxemic apnea of equal duration (time-matched responses) and by 98 +/- 41% and 4.9 +/- 2.0 mmHg, respectively, during hyperoxic apnea (P < 0.05 for hypoxemic vs. hyperoxic apnea for both). Thus, in awake healthy humans, activation of the arterial chemoreflex by hypoxemia appears to contribute importantly to the sympathetic and blood pressure responses to apnea. PMID- 7868457 TI - Free fatty acid metabolism in aerobically fit individuals. AB - The impact of aerobic fitness level on the production and disposal of serum free fatty acids was investigated in 26 normal young volunteers. The fitness level was ascertained by history and confirmed by determination of maximal aerobic capacity. Energy expenditure and substrate oxidation at rest were measured with indirect calorimetry. Free fatty acid turnover was measured with an infusion of [14C]palmitic acid. All tests were done > or = 48 h after the last bout of exercise. The sedentary (SED) volunteers had higher rates of systemic delivery of fatty acids than aerobically fit (FIT) individuals (532 +/- 53.4 vs. 353 +/- 62.3 mumol/min; P = 0.05). This difference was accentuated when the values were normalized to fat-free mass (9.2 +/- 0.8 and 5.9 +/- 0.98 mumol.kg-1.min-1 for SED and FIT, respectively). Fatty acid oxidation was similar between FIT and SED volunteers in absolute numbers (209 +/- 25 vs. 202 +/- 21 mumol/min, respectively; NS) as well as when normalized to fat-free mass (3.8 +/- 0.9 vs. 3.6 +/- 1.4 mumol.kg-1.min-1, respectively; NS). In contrast, the nonoxidative disposal of serum fatty acids was higher in SED (330 +/- 46.1 mumol/min) than in FIT individuals (144 +/- 52 mumol/min; P = 0.026). Thus, the ratio of nonoxidative to oxidative disposal rates of fatty acids was higher in SED than in FIT individuals (1.65 +/- 0.29 vs. 0.75 +/- 0.17; P = 0.021). The data support the hypothesis that high aerobic fitness level is associated with a low rate of systemic delivery of fatty acids at rest. Nevertheless, subjects with high aerobic fitness levels have fat oxidation at the same rate as unfit individuals. PMID- 7868458 TI - Initial fall in skeletal muscle force development during ischemia is related to oxygen availability. AB - We examined the hypothesis that the initial decline (first 1-2 min) in force development that occurs in working muscle when blood flow is halted is caused by O2 availability and not another factor related to blood flow. This was tested by reducing O2 delivery (muscle blood flow X arterial O2 content) to working muscle by either stopping blood flow [ischemia (I)] or maintaining blood flow with low arterial O2 content [hypoxemia (H)]. If initial decline in force development were similar between these two methods of reducing O2 delivery, it would suggest O2 availability as the common pathway. Isolated dog gastrocnemius muscle was stimulated at approximately 60-70% of maximal O2 uptake (1 isometric tetanic contraction every 2 s) until steady-state conditions of muscle blood flow and developed force were attained (approximately 3 min). Two conditions were then sequentially imposed on the working muscle: I, induced by shutting off pump controlling arterial perfusion of the muscle and clamping venous outflow, and H, induced by perfusing the muscle with deoxygenated blood (collected before testing while animal breathed N2) at steady-state blood flow level. Rates of the fall in force production in 17 matched conditions of H and I (approximately 40 s for each condition) were compared in 6 muscles tested. The blood perfusing the muscle during H had arterial PO2 = 8 +/- 1 (SE) Torr, arterial PCO2 = 37 +/- 1 Torr, and arterial pH = 7.39 +/- 0.03. The rate of decline in developed force was not significantly different (P = 0.46) between the 17 matched conditions of H (0.66 +/- 0.10 g force.g mass-1.s-1) and I (0.79 +/- 0.15 g force.g mass-1.s-1). These findings suggest that the initial fall in developed force in working skeletal muscle that occurs with ischemia is related to O2 availability. PMID- 7868459 TI - Effects of sprint cycle training on human skeletal muscle. AB - Eleven men sprint trained two to three times per week for 6 wk to investigate possible exercise-induced slow-to-fast fiber type conversions. Six individuals served as controls. Both groups were tested at the beginning and end of the study to determine anaerobic performance and maximal oxygen consumption. In addition, pre- and postbiopsies were extracted from the vastus lateralis muscle and were analyzed for fiber type composition, cross-sectional area, and myosin heavy chain (MHC) content. No significant changes were found in anaerobic or aerobic performance variables for either group. Although a trend was found for a decrease in the percentage of type IIb fibers, high-intensity sprint cycle training caused no significant changes in the fiber type distribution or cross-sectional area. However, the training protocol did result in a significant decrease in MHC IIb with a concomitant increase in MHC IIa for the training men. These data appear to support previous investigations that have suggested exercise-induced adaptations within the fast fiber population (IIb-->IIa) after various types of training (endurance and strength). PMID- 7868460 TI - Role of Ca2+ in protecting the heart from hyperkalemia and acidosis in the rabbit: implications for exercise. AB - Catecholamines can offset the negative effect of acidosis and raised extracellular K+ concentration in the isolated rabbit heart when these factors are changed with similar kinetics and concentrations as those observed in exercise. This effect appears to be mediated by changes in Ca2+ handling in the heart. To test the role of Ca2+ in vivo, we studied the interactive effects of infusions of KCl, lactic acid, norepinephrine (NE), and CaCl2 on cardiovascular performance in the anesthetized rabbit. After propranolol, CaCl2 was given during acidosis and hyperkalemia. Acidosis (arterial pH 7.17 +/- 0.3) markedly reduced cardiac performance, and its effects were exacerbated by hyperkalemia (7.3 +/- 0.4 mM). NE reversed the cardiac response to combined acidosis and hyperkalemia. After propranolol, arterial pH and arterial K+ concentration changed more rapidly with acidosis and hyperkalemia, combined with a faster fall in cardiac performance, but CaCl2 offset these negative hemodynamic effects. The rises in plasma Ca2+, NE, and sympathetic activity during exercise may therefore interact to ameliorate the harmful effects of acidosis and hyperkalemia. PMID- 7868461 TI - Osmolality alters tracheal blood flow and tracer uptake in anesthetized sheep. AB - Changes in the osmolality of airway surface liquid cause bronchoconstriction, mucus secretion, and ion transport, but little is known about the effects on the permeability of the trachea to drugs applied to the tracheal lumen. Using the anesthetized sheep, we have investigated the effects of hyperosmolar (725 +/- 11 mosmol/kg) and hyposmolar (128 +/- 5 mosmol/kg) Krebs-Henseleit (KH) solution in the tracheal lumen (mean volume 13.6 ml) on the uptake of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA), a low-molecular-mass hydrophilic tracer that is thought to cross the epithelium via paracellular pathways, and on blood flow. All changes in osmolality were made by altering the NaCl content. We perfused a tracheal artery and collected tracheal venous blood. Hyperosmolar KH increased water movement into the lumen (+2.0 ml) and solute flux out of the lumen. It increased arterial (+24.5%) and venous (+20.6%) flows and decreased 99mTc-DTPA concentration (-26.3%) and output (-12.0%) in venous blood. Hyposmolar KH caused water movement out of the lumen (-0.9 ml) and solute flux into the lumen. It had no effect on arterial (+0.6%) and venous (+5.5%) flows and greatly increased the concentration (+345%) and output (+375%) of 99mTc-DTPA in venous blood. The baseline permeability coefficient for 99mTc-DTPA (-9.1 x 10(-7) cm/s) was not affected by hyperosmolar KH (-8.7 x 10(-7) cm/s) but was increased by hyposmolar KH (-21.4 x 10(-7) cm/s). These results confirm that hyperosmolar liquid in the lumen increases blood flow and indicate that tracer uptake is affected by the bulk flow of water across the airway wall. PMID- 7868462 TI - Restricted postexercise pulmonary diffusion capacity does not impair maximal transport for O2. AB - We evaluated whether the postexercise reduction of pulmonary diffusion capacity for carbon monoxide (DLco) is influenced by a second bout of rowing and whether it affects arterial O2 tension during maximal exercise. After exercise, DLco was reduced [from a median of 37 (range of 30-44) to 34 (27-40) ml.min-1.mmHg-1; n = 21; P < 0.001], and both the membrane diffusion capacity [from 80 (58-139) to 68 (54-104) ml.min-1.mmHg-1] and the pulmonary capillary blood volume [from 88 (74 119) to 79 (61-121) ml; P < 0.01] were affected. A second bout of exercise did not influence DLco or membrane diffusion capacity (n = 7), but during both bouts arterial O2 tension was reduced [from 105 (91-110) to 91 (77-102) Torr; P < 0.001] and arterial O2 saturation decreased [from 0.98 (0.97-0.99) to 0.95 (0.86 0.96); P < 0.001]. Furosemide (iv) did not affect DLco (n = 7), suggesting that it was influenced by the central blood volume rather than by pulmonary edema. PMID- 7868463 TI - Effects of infused epinephrine on slow phase of O2 uptake kinetics during heavy exercise in humans. AB - We tested the hypothesis that infused epinephrine (Epi) would augment the slow phase of oxygen uptake (VO2) during heavy exercise. Six normal healthy males initially performed a ramp test on a cycle ergometer to estimate the lactate threshold (LT) and determine peak VO2. Each subject then performed two 20-min constant-load tests at a power output calculated to elicit a VO2 equal to estimated LT + 0.2(peak VO2--estimated LT) under control conditions throughout and with an intravenous infusion of Epi from minutes 10 to 20 at a rate of 100 ng.kg-1.min-1. Pulmonary gas exchange variables were determined breath by breath. Arterialized venous blood was repeatedly sampled from the dorsum of the heated hand. Epi infusion elevated (P < 0.05) plasma Epi concentration (i.e., from 420 +/- 130 pg/ml at minute 10 to 2,190 +/- 410 pg/ml at minute 20) but had no effect on plasma norepinephrine or K+ concentrations. Concentrations of blood lactate and pyruvate were increased, pH was decreased, and base excess became more negative by infusion of Epi (P < 0.05). Epi infusion increased (P < 0.05) CO2 production and the respiratory exchange ratio but had no effect on ventilation or VO2. VO2 increased (P < 0.05) to the same extent in both control (3.14 +/- 0.12 l/min at minute 10, 3.28 +/- 0.12 l/min at minute 20) and Epi infusion (3.10 +/- 0.11 l/min at minute 10, 3.25 +/- 0.11 l/min at minute 20) trials. We therefore concluded that neither Epi nor its associated humoral consequences contribute significantly to the slow phase of VO2 kinetics during heavy exercise. PMID- 7868464 TI - Changes in potassium contractures due to simulated weightlessness in rat soleus muscle. AB - Some contractile properties of soleus muscle (SOL) fibers isolated from tail suspended (21 days) rats were compared with those determined in the slow-twitch SOL and the fast-twitch extensor digitorum longus muscle (EDL) of control rats. In SOL from suspended rats, the resting membrane potential and the intracellular Na+ activity were typical of fast-twitch muscles. The relationship between the amplitude of K+ contractures and the membrane potential was steeper for control SOL than for control EDL and suspended SOL. The inactivation curve was also shifted to more positive potentials after suspension. In the presence of perchlorate anions, the tension activation curves of control EDL and suspended SOL were similarly shifted to more negative potentials. Thus, in the present study, modifications induced by suspension in SOL, mainly related to changes in the voltage-sensing process involved in the excitation-contraction coupling mechanism, were that the SOL assumed some of the characteristics of fast-twitch muscles. PMID- 7868465 TI - Microvascular responses to body tilt in cutaneous maximus muscle of conscious rats. AB - We investigated microvascular responses to head-up tilt (HUT) and head-down tilt (HDT) in striated muscle of conscious male rats (n = 15; body wt 163 +/- 5 g). To observe the microcirculation in the cutaneous maximus muscle, a transparent polycarbonate chamber (1.5 cm diam) was implanted aseptically into a skin fold created between the shoulders. Rats were trained to sit quietly during HUT and HDT while positioned on a horizontal microscope that rotated in the sagittal plane. At 4-5 days after surgery, arteriole and venule diameters were recorded using videomicroscopy while the rat experienced 10 min each (in random order) of HUT or HDT at 20 degrees or 40 degrees separated by 2-h rest periods. HUT had no affect on microvessel diameter; 20 degrees HDT had little affect. In response to 40 degrees HDT, "large" arterioles (88 +/- 18 microns; n = 10) constricted by 18 +/- 2% (P < 0.05) and "small" arterioles (40 +/- 17 microns; n = 7) dilated by 21 +/- 3% (P < 0.05); this difference suggests variation in mechanisms controlling arteriolar responses. Venules (45 +/- 22 microns; n = 9) exhibited a larger fluctuation in diameter (amplitude 13 +/- 5 microns) during 40 degrees HDT compared with other body positions (amplitude typically 2-3 microns), suggesting that venomotor activity may be induced with sufficient fluid shift or change in central venous pressure. These observations illustrate a viable model for studying microvascular responses to gravitational stress in conscious rats. PMID- 7868466 TI - Effects of N-acetylcysteine on in vitro diaphragm function are temperature dependent. AB - Recent evidence has shown that systemic administration of N-acetylcysteine (NAC), a compound structurally similar to the intracellular antioxidant glutathione, inhibits skeletal muscle fatigue. To further elucidate the actions of NAC, we studied its effects on in vitro rat diaphragm contractile function. Rat diaphragm strips were incubated in tissue baths containing physiological salt solution (n = 29) or physiological salt solution containing 4 mg/ml of NAC (n = 29). Strips were stimulated by either indirect or direct means. After determination of baseline contractile characteristics, strips were fatigued for 4 min at 20 Hz (1 train/s, 0.33 ms train duration). Force-frequency relationships were then studied over a 60-min recovery period. We found that 1) NAC had significant effects on the baseline force-frequency relationship; treated strips had increased peak tension but diminished twitch tension and accelerated twitch kinetics; 2) NAC had significant fatigue-sparing effects that were magnified at 37 degrees C; and 3) NAC treatment did not improve postfatigue recovery. The effects of NAC were generally independent of the stimulation method. We conclude that NAC has direct temperature-dependent effects on diaphragm function. These effects are consistent with the properties of NAC as an antioxidant and suggest important but complex effects of oxidant stress on skeletal muscle. PMID- 7868467 TI - Hyperinflation with intrinsic PEEP and respiratory muscle blood flow. AB - Increased end-expiratory lung volume and intrinsic positive end-expiratory pressure (PEEP) are common in obstructive lung disease, especially during exacerbations or exercise. This loads the respiratory muscles and may also stress the circulatory system, causing a reduction or redistribution of cardiac output. We measured the blood flow to respiratory muscles and systemic organs using colored microspheres in 10 spontaneously breathing anesthetized tracheotomized dogs. Flows during baseline breathing (BL) were compared with those during hyperinflation (HI) induced by a mechanical analogue of airway closure and with those during an inspiratory resistive load (IR) that produced an equivalent increase in inspiratory work and time-integrated transdiaphragmatic pressure. Cardiac output was unchanged during IR (3.19 +/- 0.27 l/min at BL, 3.09 +/- 0.34 l/min during IR) but was reduced during HI (2.14 +/- 0.29 l/min; P < 0.01). Among the organs studied, flow was unaltered by IR but decreased to the liver and pancreas and increased to the brain during HI. For the respiratory muscles, flow to the diaphragm increased during IR. However, despite a 1.9-fold increase in inspiratory work per minute and a 2.5-fold increase in integrated transdiaphragmatic pressure during HI, blood flow to the diaphragm was unchanged and flow to the scalenes and sternomastoid fell. The only respiratory muscle to which flow increased during HI was the transversus abdominis, an expiratory muscle. We conclude that the circulatory effects of hyperinflation in this model impair inspiratory muscle perfusion and speculate that this may contribute to respiratory muscle dysfunction in hyperinflated states. PMID- 7868468 TI - Cardiovascular and renal nerve responses to static muscle contraction of decerebrate rabbits. AB - The purpose of this study was to determine whether the biphasic arterial blood pressure responses elicited by static muscle contraction of decerebrate rabbits are mediated, at least in part, by an initial decrease and a subsequent increase in sympathetic outflow. Renal sympathetic nerve activity (RSNA) was used as an index of sympathetic outflow. Static contraction of the triceps surae muscle (n = 14) initially decreased mean arterial blood pressure (MAP) -20 +/- 3 mmHg and heart rate (HR) -15 +/- 5 beats/min (nadir values). After this initial decrease, MAP increased 12 +/- 2 mmHg (peak increase) above baseline and there was a tendency for HR to be elevated (6 +/- 3 beats/min). The changes in RSNA during muscle contraction (n = 6) mirrored the nadir and peak responses of MAP (-50 +/- 9 and 32 +/- 11%). Muscle stretch (n = 11) also evoked similar nadir and peak responses of MAP (-20 +/- 5 and 9 +/- 1 mmHg), HR (-17 +/- 7 and 3 +/- 3 beats/min), and RSNA (-43 +/- 9 and 46 +/- 15%). These data suggest that the initial depressor and subsequent pressor responses elicited by skeletal muscle contraction and stretch are mediated, at least in part, by biphasic changes in sympathetic outflow. PMID- 7868469 TI - Metabolic and work capacity of skeletal muscle of PFK-deficient dogs studied in situ. AB - Mechanical and metabolic relationships of muscle lacking phosphofructokinase (PFKD) activity were compared with muscle having normal phosphofructokinase (NORM) activity by using the gastrocnemius-plantaris muscle group with isolated circulation in situ. Muscle contractile properties were similar in both groups. Initial power output (W) during repetitive tetanic (200 ms, 50 impulses/s) isotonic contractions was similar in both groups; however, W declined significantly more (30-80%) in PFKD than in NORM muscle over time, with a constant O2 uptake (VO2)/W. Despite similar O2 and substrate delivery, PFKD muscle had a lower VO2 (42-55%), less glucose uptake, similar free fatty acid uptake, and lactic acid uptake rather than output, during contractions. Muscle venous H+ concentration, strong ion difference, and PCO2 increased during contractions, the magnitude of change being smaller in PFKD muscle. Elevating arterial lactate concentration before contractions in PFKD muscle resulted in significant improvements in W and VO2 without altering the acid-base exchange at the muscle. Increasing O2 delivery by increasing arterial O2 concentration in PFKD dogs did not improve W or VO2. We conclude that, despite no inherent mechanical or contractile differences, PFKD muscle has a severely limited oxidative capacity and exaggerated fatigue and blood flow responses to contractions due to limited substrate metabolism resulting from the inability to utilize glycogen and/or glucose. PMID- 7868470 TI - Geometry of respiratory phase switching. AB - A second-order ordinary differential equation is outlined for the temporal dynamics of the respiratory central pattern generator (RCPG). Recurrent interactions between central excitation and inhibition confine the breathing cycle to the interior of a heteroclinic orbit between switching points (saddle equilibria) located at end expiration (E-I) and end inspiration (I-E). Dynamics depend on four eigenvalues that control inspiratory drive (lambda), excitability of inspiratory off switch (omega 1; stage 1 expiration), rate of central excitation disinhibition (omega 2; stage 2 expiration), and damping of the oscillator (epsilon). Ratios omega 2/lambda and omega 1/lambda determine local E I and I-E phase switching, whereas inspiratory-to-expiratory balance varies as omega 2/(lambda omega 1). Stable apnea is seen when (lambda omega 2)/epsilon is near zero; inspiratory apneusis is seen when (lambda omega 1)/epsilon is low. The equations provide formalisms for discussing phase switching, apneas, apneuses, phase resetting and singularities, rapid shallow breathing, postinhibitory rebound excitation, redundancy, gating within the RCPG, and behavioral control of breathing. The model is offered as an explicit alternative to the harmonic oscillator models that have been used in the past to describe RCPG function. PMID- 7868471 TI - Symmetry, bifurcations, and chaos in a distributed respiratory control system. AB - A multivariate model is outlined for a distributed respiratory central pattern generator (RCPG) and its afferent control. Oscillatory behavior of the system depends on structure and symmetry of a matrix of phase-switching functions (F omega, phi) that control distribution of central excitation (CE) and inhibition (CI) within the circuit. The matrix diagonal (F omega) controls activation of CI variables as excitatory inputs are altered (e.g., central and afferent contributions to inspiratory off switch); off-diagonal terms (F phi) distribute excitations within the CI system and produce complex eigenvalues at the switching points between inspiration and expiration. For null F phi, phase switchings of saddle equilibria located at end expiration and end inspiration are overdamped all-or-nothing events; graded control of CI is seen for phi > 0. When coupling is significant (phi >> 0), CI dynamics become underdamped, admitting a domain of inputs where chaotic behavior is predictably observed. For the homogeneous RCPG (symmetric F omega, phi), CE oscillations are one-dimensional limit cycles (D = 1) or weakly chaotic (D approximately equal to 1). When perturbations from symmetry are significant, the distributed RCPG becomes partitioned where strongly chaotic oscillations (D > or = 2) and central apnea (D = 0) are seen more frequently. The equations provide means for mapping Silnikov bifurcations that alter the geometry and dimension of the breathing pattern and formalisms for discussing RCPG processing of afferent information. PMID- 7868472 TI - Use of scaling theory to relate measurements of lung endothelial barrier permeability. AB - This work examined the relationships between lung microvascular permeability surface area products (PS) for small solutes in animals of different size and for columns of endothelial-covered microcarrier beads. We assembled PS data (humans, sheep, lambs, and rabbits) for labeled sucrose, mannitol, urea, 1,2-propanediol, 1,3-propanediol, and 1,4-butanediol. In addition, PS for cell columns using sucrose, mannitol, and sodium fluorescein were evaluated. A new mathematical model for the analysis of cell columns that accounts for transit time variations was derived and compared with models neglecting this variation. Allometric relationships between PS and body weight or exchange surface (S) were examined. Permeability relative to diffusivity (P/D) correlated inversely with S for all animals. In addition, P/D for the cell columns fell near this regression line. The results suggest either that permeability for hydrophilic tracers is higher for smaller animals or that the indicator-dilution measurement is a fractal process dependent on scale. Furthermore, the P/D-S correlations may help relate cell column experiments to animal studies. PMID- 7868473 TI - A simple isokinetic cycle for measurement of leg muscle function. AB - The measurement of net pedaling torque during isokinetic cycling allows for the evaluation of leg muscle strength and work capacity over fixed time intervals. However, the expense and difficulty of constructing an isokinetic cycle have limited the widespread application of this useful research tool. We have modified a simple commercially available isokinetic cycle that uses hydraulics to maintain pedaling velocity. A strain gauge on the flywheel axle strut measures the torsion on the strut caused by pedaling. To evaluate this device, seven healthy subjects (3 males and 4 females) were each tested twice at 60, 90, and 120 rpm for peak power during a 10-s sprint and at 100 rpm for total work performed during a 30-s sprint. These results were compared with predicted values for age, height, and sex developed on a more complicated isokinetic cycle. Subjects also performed a progressive cycle ergometry test. For the group, peak power was 97.30 +/- 12.64% of predicted (males 883.70 +/- 202.76 W; females 657.00 +/- 66.42 W) and work output was 107.70 +/- 15.75% of predicted (males 15.50 +/- 2.85 kJ; females 11.70 +/- 2.17 kJ), whereas maximal progressive exercise capacity was 126.40 +/- 25.84% (males 245.30 +/- 56.58 W; females 212.30 +/- 35.49 W). The relatively lower work values generated on this cycle (compared with the maximal progressive exercise capacity) can be attributed to the location of the strain gauge, resulting in measurement of effective work output on the flywheel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868475 TI - Primary cardiac amyloidosis. PMID- 7868474 TI - Arginine vasopressin and secretion of fetal lung liquid. PMID- 7868476 TI - New regulatory CD4 reporting to assist Arkansas AIDS case surveillance. PMID- 7868477 TI - Radiological case of the month. Mediastinal goiter. PMID- 7868478 TI - Smoke and mirrors. PMID- 7868479 TI - Hot Springs waters and the treatment of venereal diseases: the U.S. Public Health Service Clinic and Camp Garraday. AB - Hot Springs, Arkansas and healing have been almost synonymous since the Indians lived in the area. From the end of World War I until the early 1940s, venereal disease patients flocked to Hot Springs for treatment. The primary focus of this paper is to tell the story of the facilities built to provide treatment. The government at both the federal, state, and local levels had to accommodate the great demand for treatment. The U.S. Public Health Service Clinic and Camp Garraday at Hot Springs were two major facilities built to meet that demand. Almost forgotten today, these two establishments afforded many patients the opportunity for healing unavailable in local situations. The Clinic provided the best treatment available and performed needed research studies on venereal disease during its peak years. PMID- 7868480 TI - Ten ways to alienate a patient during one office visit. PMID- 7868481 TI - Hirudin. PMID- 7868482 TI - Radiological case of the month. Osler-Weber-Rendu disease (pulmonary arteriovenous malformation). PMID- 7868483 TI - Psoriatic arthritis and methotrexate. PMID- 7868484 TI - Methotrexate in psoriatic arthritis. AB - Thirty three patients with psoriatic arthritis were treated with starting dose of 7.5 mg of methotrexate orally, every week for a period of 6 months to 7 years (mean 2.2 years) along with non-steroidal anti-inflammatory agents. The dose of methotrexate during the course of therapy ranged 5 to 15 mg/week (mean 7.8 mg). There was complete to partial remission in arthritis and psoriatic skin lesions in 94% (31) patients. No response was noticed in 2 patients. Regular monitoring of haematological, renal and liver function tests was done. No significant side effects of the drug, requiring discontinuation of the therapy, were seen during the treatment. Methotrexate can be used early in the course of psoriatic arthritis with good results. PMID- 7868485 TI - Helicobacter pylori in normal gastric mucosa. AB - Since the discovery of Helicobacter pylori (H. pylori) in 1983 several studies have established relationship of H. pylori with gastritis, duodenal ulcer disease and gastric carcinoma. H. pylori infection is widely prevalent and exposure occurs at younger age in our country. Several Western studies have shown prevalence of H. pylori in normal gastric mucosa to range from 0-25%. As similar information is not available from our country we estimated the prevalence of H. pylori in histologically normal gastric mucosa. Of the 50 asymptomatic volunteers studied, 33 showed histological evidence of gastritis and 28 of these were H. pylori. We conclude that histological gastritis is very common in young asymptomatic Indians and H. pylori infection is noticed in almost 25% subjects with histologically normal gastric mucosa. PMID- 7868486 TI - Biliary strictures on ERCP: a study in northern India. AB - Case records of 82 patients with biliary stricture diagnosed on endoscopic retrograde cholangiopancreatography (ERCP) during a 7-years period (1983-89) were analysed for its aetiology, clinical presentation, laboratory abnormalities and radiological characteristics. The aetiology was found to be benign in 59 and malignant in 23 patients. Forty seven percent of all strictures were post cholecystectomy strictures (PCS). Presence of mucosal irregularity and incomplete stricture were commoner with malignancy. Malignant biliary strictures (MBS) were commonly seen in males, occurred at older age, had short history, had higher alkaline phosphtase and serum bilirubin values when compared to patients with benign biliary strictures (BBS). PMID- 7868487 TI - Critically ill Guillain Barre' syndrome. AB - Among the 153 patients fulfilling NINDS criteria for Guillain Barre' Syndrome (GBS) seen over 5.5 yrs, there were 47 (M:F 38.9) critically ill patients (age range 4 to 60 years). Antecedent event was recorded in 25 patients and the peak deficit was attained over a mean period of 9.5 days. Besides severe motor paralysis other salient features were: bulbar paralysis--42, sensory symptoms or signs--21, dysautonomia 31 and requirement for ventilatory assistance 45. CSF protein was raised in 63% cases. All the 17 patients who underwent electromyography had abnormalities of nerve conduction paramentes. Mean stay on the ventilator was 29.6 days and was not influenced by corticosteroid. Complications were frequent: pulmonary and urinary tract infection, dysautonomia, electrolyte disturbances, haemetmesis, bleeding from tracheostomy site and hepatic and renal failure. Mortality in steroids treated group (13/27) and the conservatively managed group (5/20) did not differ significantly. No discriminant factor emerged between survivors and non-survivors. Age and sex of the patients, presence of antecedent event, onset to peak interval and CSF protein level did not predict the need for ventilatory assistance, although these patients at admission had more frequent weakness of facial, bulbar, trunk, neck and proximal muscles of upper limbs and autonomic disturbances. Course of GBS remains unpredictable at the onset of the disease, warrants close supervision and meticulous supportive care and remains a therapeutic challenge. PMID- 7868488 TI - Comparison of serum and breast milk ferritin with some hematological parameters in the perinatal period. AB - Hemoglobin, hematocrit, serum iron, total serum iron binding capacity, transferrin saturation and ferritin levels of 27 pregnant women and their babies at delivery and at 8-10 weeks of age and of their mature breast milk were determined. Eighteen pregnant women with iron deficiency anemia and 9 healthy pregnant women as controls constituted the groups in this study. Excepting serum iron (p < 0.05) no significant differences were found between any of the remaining parameters in cord blood of the anemic and control groups. While the hematological parameters in sera of babies of the anemic and control mothers showed no significant differences at 8-10 weeks of age, the mean ferritin level at 8-10 weeks in breast milk of anemic mothers was significantly lower than of controls (p > 0.02). Besides, a significant relation (r:0.535) was found between the ferritin values of the cord blood and of the infants' sera at 8-10 weeks of age. PMID- 7868489 TI - Blood pressure profile, urinary sodium and body weight in the 'Oraon' rural and urban tribal community. AB - Blood pressure and nutritional profiles in the 'Oraon' tribal community of India living in rural and urban areas were studied between 1981-85 after a house to house survey of 4523 rural tribal people (RT) and 935 of their urban tribal counterparts (UT). Prevalence of hypertension was found to be 4.8/1000 males and 4.3/1000 females in rural tribal group giving an overall rate of 4.6/1000. In contrast the same were 27.1/1000 males and 21.4/1000 females in UT group, overall rate being 25.6/1000. Average calorie consumption were 1750 and 2280 and mean 24 hour-urinary sodium excretions 58 and 118 milliequivalents in RT and UT groups respectively. Of the total of 21 subjects in RT and 24 in UT detected to be hypertensive, 7 had common family inheritance. Increased mean arterial pressure correlated with increased sodium consumption and body weight. Hypertensives from both the groups showed higher urinary sodium excretion (P < 0.05). This epidemiologic study proves the role of a genetic factor/defect complicated by higher salt consumption in causation of increased blood pressure. PMID- 7868490 TI - Effect of rifampicin on theophylline pharmacokinetics in human beings. AB - Theophylline pharmacokinetics before and after rifampicin administration was studied in 10 healthy volunteers. It was seen that Rifampicin significantly increased the volume of distribution of theophylline by 23.41% (p < 0.01) and its metabolic clearance by 47.65% (P < 0.05). This has got clinical significance in the treatment of patients of pulmonary tuberculosis with chronic obstructive airways disease where both the drugs may have to be given concurrently. PMID- 7868491 TI - Alteration in blood gases in tetanus. AB - Tetanus is an important cause of patient mortality. Hypoxia is an important determinant of poor prognosis in tetanus. Oxygen saturation (Sa02) determines effectiveness of muscle relaxants. We performed arterial blood gas (ABG) studies in 20 patients with tetanus and 20 controls. All patients had hypoxemia and metabolic acidosis at admission. The mortality rate in patients with admission PaO2 < 70mm Hg was higher compared to those with PaO2 > 70mm Hg (P < 0.01). Patient with pH < 7.2 had higher mortality compared to those with pH > 7.2 (p < 0.05). Severe hypoxemia and severe metabolic acidosis connoted poor prognosis. PMID- 7868492 TI - Sickle cell syndromes in and around Bardoli. AB - The study comprised of 2 groups. In group I sickling test was done in students studying in a school which mainly caters to the educational needs of the backward community. Out of 130 students examined 24 were found to be sicklers. The distribution of this cases among various castes/tribes were as follows- Choudharys (Cd)-13, Gamits (Gt)-4, Dhodhia Patels (DP)-4, Koknis (K)-2 and Koli Patel (KP)-1. In group II, patients admitted in the hospital between Jan '81 to June '82 were studied. The prevalence of sickle cell syndrome was 1.74%. The most common mode of presentation were limb pains and weakness. Hemoglobin values ranged from 3.0 gram% to 12 gms%. 35 cases of HbSS, 149 cases of HbAS and 1 case of Sickle Beta thalassemia were seen. The distribution of the cases amongst the various tribes and castes were as follows-Cd-93, Gt-56, DP-23, KP-7, K-4 and Rathods (R)-2. No cases were found in Anavil Brahmins or Patidar Patels. Clinical and pathological observations included palpable splenomegaly in 54 cases, splenic abscess in 1 case, isothenuria in large number of patients, microscopic hematuria in 6 cases and frank hematuria in 1 case. Osteomyelitis and cholecystitis were seen in one case each. PMID- 7868493 TI - Methotrexate for rheumatoid arthritis. PMID- 7868494 TI - Drug induced rheumatic disorders. PMID- 7868495 TI - Carotenes: a ray of hope in prevention of cardiovascular disorders, cancers and cataract. PMID- 7868496 TI - Pneumothorax as the presenting manifestation of lymphangitis carcinomatosa. PMID- 7868497 TI - Hodgkin's disease presenting as nephrotic syndrome. PMID- 7868498 TI - Septicaemia caused by Aeromonas hydrophilia in a neonate. PMID- 7868499 TI - Myoglobinuric renal failure following rhabdomyolysis. PMID- 7868500 TI - Unusual presentation of Alport syndrome. PMID- 7868501 TI - Multiplane transesophageal echocardiography for the diagnosis of acute aortic dissection. PMID- 7868502 TI - A rare case of Aicardi syndrome. PMID- 7868503 TI - Cytomegalovirus colitis in a patient with Castleman's disease. PMID- 7868504 TI - Acute hepatic failure in aluminium phosphide poisoning. PMID- 7868505 TI - Which typhus fever? PMID- 7868506 TI - Radio iodine induced thyroid storm. PMID- 7868507 TI - Autonomic nervous system--not forgotten. PMID- 7868508 TI - Isoniazid therapy in cerebellar ataxia. PMID- 7868509 TI - Pregnancy with idiopathic thromocytopenic purpura. PMID- 7868510 TI - IV quinine in malaria. PMID- 7868511 TI - Atrial fibrillation with hypertensive crisis. PMID- 7868512 TI - Hydrophobia: why a unique symptom of rabies. PMID- 7868513 TI - Multiresistant Salmonella paratyphi 'A' infection in coastal Karnataka. PMID- 7868514 TI - L1 arthropathy syndrome. PMID- 7868515 TI - Insulin resistance and hypertension. PMID- 7868516 TI - Metered dose inhalers--practical considerations and correct use. PMID- 7868517 TI - A study of hyperinsulinaemia in Indian hypertensive subjects. AB - Fasting and 2 hours post-prandial serum insulin levels were estimated in 100 hypertensive subjects and 25 matched, healthy controls, by radio-immuno assay (RIA). Seventy four of the 100 hypertensives exhibited fasting hyperinsulinaemia. Post-prandial hyperinsulinaemia was present in 85 hypertensives. None of the healthy individuals demonstrated hyperinsulinaemia. Although, most hyperinsulinaemic patients exhibited an abnormal lipo-protein profile, there was no statistical correlation between absolute values of lipo-protein and insulin. PMID- 7868518 TI - Faulty use of metered dose inhalers by physicians. AB - A questionnaire regarding use of metered dose inhalers (MDI) was administered to 38 physicians, 9 faculty members and 29 residents. Fifty-five percent of faculty members answered at least three or more of the seven steps of inhalation technique correctly as compared with 86% of residents, this was statistically significant (p value < 0.01). All the participants used to prescribe MDI to their patients. 80% of them responded that they followed package insert instructions to educate their patients. It was concluded that doctors involved with MDI use, should learn and become familiar with proper recommendation for its optimal aerosol delivery. PMID- 7868519 TI - Pancreatic xenograft survival in diabetic rabbits. AB - Prolonged survival of pancreatic xenografts in the muscles of diabetic rabbits was achieved. The mean graft survival time (assessed by euglycemic status) in nonimmunosuppressed (Group A) was 10 days and in immunosuppressed (Group B) was 36 days (P < 0.05). Adequate immunosuppression helps pancreatic xenograft to normalize blood glucose level (BGL) by prolonging survival time. Our study demonstrates that xenotransplantation of islet cells in their natural environment (pancreatic tissue in four of thin slices) survive and function adequately in immunosuppressed recipients. This discordant Xenotransplantation model may be useful for future xenotransplantation studies. PMID- 7868520 TI - Endocrine profiles in six patients with acanthosis nigricans. AB - Six women (age range 17-38 years), who presented to the dermatology services with biopsy-proven acanthosis nigricans of variable duration were evaluated to rule out endocrine diseases. Menstrual abnormalities (5/6 patients), pallid striae (4/6 patients), hirsutism (4/6 patients) and acne vulgaris (2/6 patients) were found on physical examination. All the patients had body mass indices in the obese (> 27 kg/m2) range, and in association we found ovarian hyperthecosis, PCOD, premature ovarian failure, glucose intolerance and hyperprolactinaemia in the above six patients. The importance of appropriate endocrinal evaluation in patients with biopsy-proven acanthosis nigricans is emphasized. PMID- 7868521 TI - Assessment of upper airway obstruction by pulmonary function testing. AB - Twenty-five cases of upper airway obstruction (UAO) of different diseases and ten normal healthy controls were studied by deriving parameters from raw data on Gould System-21 Pulmonary Work station. All the obstructive lesions were confirmed under direct visualisation by fibreoptic bronchoscopy or indirect laryngoscopy. It was observed that FEF 50%/FIF 50% ratio above 1 was the best diagnostic indicator for fixed and variable extrathoracic UAO (p < 0.02). FEV1/PEFR was altered significantly (p < 0.001) and value above 10 ml/Litre/min was the second best parameter to recognise UAO. FEV1 0.5 < or = 1.5 (p < 0.001) and FIF 50% < 100 Lit/min were also suggestive of UAO. Flow volume loop remained the most sensitive method to detect UAO but only 15 patients could construct it. These altered parameters returned to normal after the surgical removal of obstruction which was possible in three cases. PMID- 7868522 TI - A combination of sulphadiazine, trimethoprim and metronidazole or tinidazole in kala-azar. AB - Nine patients of kala-azar showed good response to treatment with a combination of sulphadiazine, trimethoprim and metronidazole or tinidazole given orally for 12 to 25 weeks. No untoward side effect was noticed. Tinidazole sulphadiazine and trimethoprim combination was found to be safer for treatment of kala-azar in pregnant women. PMID- 7868523 TI - Drug induced neuromuscular disorders. PMID- 7868524 TI - Thyroid failure--autoimmunity and clinical spectrum. PMID- 7868525 TI - Prevention of coronary heart disease in Indians. PMID- 7868526 TI - The clinical associations of lupus anticoagulant and anticardiolipin antibodies. PMID- 7868527 TI - Malnutrition related diabetes mellitus. PMID- 7868528 TI - Reversible neurological complications during thyrotoxic crisis. PMID- 7868529 TI - A case of dermatomyositis presenting with erythema multiforme. PMID- 7868530 TI - Acute panniculitis: a report of 2 cases. PMID- 7868531 TI - Ocular metastasis from carcinoma breast. PMID- 7868532 TI - Hypercalcemia, bony lytic lesions and leukemia. PMID- 7868533 TI - Enhanced action of acenocoumarin in hyperthyroidism. PMID- 7868534 TI - Pyeloureteritis cystica in association with nephrotic syndrome. PMID- 7868535 TI - Fellowship (FICP)--a prestigious professional addition. PMID- 7868536 TI - Dopa-responsive dystonia. PMID- 7868537 TI - Exaggerated tendency to postural hypotension with isosorbiddinitrate on clonidine's background activity. PMID- 7868538 TI - Prosthetic heart valve, antiocoagulants and cerebral hemorrhage. PMID- 7868540 TI - Treatment of early, mild Parkinson's disease. PMID- 7868539 TI - Safety of thrombolysis during menstruation. PMID- 7868541 TI - Fenugreek in diabetes mellitus. PMID- 7868542 TI - Indian medical journals: a glimpse through Science Citation Index. PMID- 7868544 TI - Whither Master Health Check-up? PMID- 7868543 TI - Malaria in pregnancy. PMID- 7868545 TI - Lipomatosis associated with small intestinal leiomyoma. PMID- 7868546 TI - Cyclic neutropenia. PMID- 7868547 TI - Thrombolysis and ventricular late potentials. PMID- 7868548 TI - Ventricular late potentials after thrombolysis. AB - High frequency low amplitude signals that prolong the terminal portion of the QRS complex in the electrocardiogram are termed late potentials (LPs). It has been established for quite some time that the presence of LPs after acute myocardial infarction (AMI) is associated with an increased risk of ventricular tachyarrythmias and sudden cardiac death (SCD), and vice versa. It is also known that thrombolytic therapy after AMI significantly decreased the incidence of ventricular tachyarrythmias and SCD. The object of this study was to find out whether thrombolysis in AMI decreased the incidence of LPs. Fifty two male patients of the age group 41-46 years with first anterior wall AMI were studied. Thirty of them presented within 6 hours of chest pain and were given intravenous streptokinase (IVSK) in addition to conventional therapy. The remaining 22 received conventional therapy but no thrombolysis. There was no significant difference in these two groups regarding age, CKMB, hypertension, diabetes, smoking, prior use of beta blockers, and ejection fraction. Eight out of the 30 patients receiving IVSK were positive for LPs as against 13 out of the 22 in the control group. This difference was statistically significant (p > 0.02 < 0.01). Thus thrombolysis in the early hours of anterior AMI diminishes the incidence of LPs. PMID- 7868549 TI - A study of culture positive multidrug resistant enteric fever--changing pattern and emerging resistance to ciprofloxacin. AB - The present prospective study was carried out to observe the changing trends in the clinical pattern and multidrug resistance in typhoid fever. Fever was the main presenting feature. Other associated features were headache, vomiting, diarrhoea, altered sensorium and jaundice. Out of 78 patients, one patient died due to enteric encephalopathy and other due to septicaemia with peripheral circulatory failure. 12 patients responded to chloramphenicol and gentamycin. 51 patients responded to ciprofloxacin, while remaining 9 patients responded to combination of cefotaxime and amikacin. Three patients showed in vitro resistance to ciprofloxacin and two out of these also showed no response in vivo. This study re-emphasises the changing pattern, prolonged course and role of quinolones especially ciprofloxacin in the management of drug resistant typhoid fever, but at the same time indicates that ciprofloxacin is not the drug of choice in all cases of typhoid fever and resistance to it may be seen in some cases, where other drugs have to be used. PMID- 7868550 TI - Limb girdle myasthenia: a study of familial and sporadic cases. AB - Chronic limb girdle myasthenia gravis (MG) is a rare entity. We describe six such patients (F:M 4:2) who constituted 5% of 120 MG cases in a seven year study. The disease was familial in four and sporadic in two. No patient had ocular muscle weakness either at presentation (mean of 18.2 months after onset of illness) or during a mean follow up period of 36 months. Diagnosis was established by a positive decremental response on repetitive stimulation of a proximal muscle. Muscle biopsy was essentially normal in all five patients. All patients responded to acetylcholinesterase inhibitors, although to varying degrees. Four patients also received steroids. One patient with sporadic MG had transient worsening but others showed partial improvement. It is noteworthy that the initial diagnosis in these patient was other than MG. Diagnosis of limb girdle myasthenia needs to have a strong index of suspicion as it has therapeutic implications. PMID- 7868552 TI - Low grade pyrexia: is it chronic fatigue syndrome? AB - Eighty seven consecutive patients presenting with prolonged low grade pyrexia (99 degrees-101 +/- F) during 1984-93 were followed up for a mean duration of 2.9 years. Mean age was 37.55 years (SD + 10.16) and 66 (75.8%) were females. Onset of pyrexia was acute in 57 patients and was associated with chilly sensation (42), Fatigue (69), Arthralgias (61), myalgias (55) and several other non specific symptoms. Clinical examination showed paucity of physical signs with 7 patients showing tender lymphadenopathy, 7 showing splenomegaly, 5 hepatomegaly, and 1 phylctenular conjunctivitis. Psychiatric examination was within normal limits. Extensive investigations for any viral or other infection, autoimmune disorder or malignancy were unrewarding. Patients were followed up for an average of 2.9 (2 to 5 years). Thirteen patients had become asymptomatic within one year of onset of symptoms, 38 by two years and 45 by the end of three years. This syndrome may be a variant of chronic fatigue syndrome. PMID- 7868551 TI - Male gonadal function in Hodgkin's disease before and after treatment. AB - Twenty eight histologically confirmed cases of Hodgkin's disease were evaluates with regard to libido, sperm count, FSH, LH and urinary ketosteroid levels, before and during different stages of chemotherapy along with testicular biopsy on 16 cases. Decrease in libido during therapy improved following treatment, 50% cases who were oligospermic before treatment became azospermic, Serum FSH levels increased significantly (p 0.001) during the course of treatment. There was no significant change in LH and urinary ketosteroid levels (p 0.05). Testicular biopsy, normal initially, showed germ cell aplasia and absence of spermatogenesis after therapy. Drug induced testicular change leads to sterility. PMID- 7868553 TI - Study of superior vena cava syndrome--aetiopathology, diagnosis and management. AB - Thirty two patients of superior vena cava syndrome (SVCS) were studied. Clinical features noted were diffuse neck swelling, breathlessness, chest pain, engorged neck veins, facial swelling and dilated engorged veins over chest wall. Radiography revealed a superior mediastinal mass in 31.2% of patients and right upper lobe mass in 50% patients. FNAC of lung showed aetiology in 34.5% patients and lymph node biopsy in 31.2% patients. Aetiology of SVCS was benign in 12.5% patients and malignant in 87.5% patients. Squamous cell carcinoma was the commonest cause of SVSC. Radiotherapy proved to be the most beneficial form of treatment. The mean survival period in patients due to malignant etiology was 6 months. PMID- 7868554 TI - Percutaneous transluminal coronary angioplasty of left main coronary artery. AB - The present study is a retrospective analysis of 15 percutaneous angioplasty procedures of the left main coronary artery performed in 12 patients (8 males (66%) with a mean age of 64 +/- 12 (range 45-79) years. Twelve dilatations were elective: 8 for unstable angina, 3 for stable angina, and 1 after a recent myocardial infarction. All elective patients were protected with at least 1 patent graft to the distal left coronary artery. Emergency dilatation for evolving myocardial infarction with cardiogenic shock was done in 3 patients. The right coronary artery was dominant in 11 cases. The mean ejection fraction was 49 +/- 18% (range 21-7%). All dilatations were done through the femoral approach. Two dilatations were performed with the "kissing balloon" technique and 2 with the "kissing wire" technique. An intra-aortic balloon counterpulsation was used in 3 cases (21%). In 8 cases (53%), 1 additional coronary artery was dilated in the same session. The technical success rate was 100% and the clinical success rate 73%. For the elective dilatations, the technical success rate was 100% and the clinical success rate 92% (11/12). Four patients died during hospitalisation (27%). The mortality rate was 100% (3/3) for emergency dilatations and 8% (1/12) for elective dilatations (patient with dilatation of 3 vessels and 1 graft in the same session). After a mean follow-up of 25 +/- 28 (rang 1-88) months, the 8 patients discharged from hospital were alive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868555 TI - Immune hemolytic anemia. PMID- 7868556 TI - Down's syndrome with acute myeloid leukemia. PMID- 7868557 TI - Post-traumatic syringomyelia. PMID- 7868558 TI - Distinction of Becker's muscular dystrophy from limb-girdle type by dystrophin analysis. PMID- 7868559 TI - A case of Salmonella bacteremia presenting with visual loss. PMID- 7868560 TI - Post renal transplant pyopericardium. PMID- 7868561 TI - Left atrial ball thrombus: echocardiographic features and clinical implications. PMID- 7868562 TI - Amyloidosis--a rare complication of psoriasis. PMID- 7868563 TI - Cyclic neutropenia. PMID- 7868564 TI - Phenformin induced lactic acidosis in an elderly NIDDM patient. PMID- 7868565 TI - Survival after attempted strangulation. PMID- 7868566 TI - Ocular involvement in sarcoidosis. PMID- 7868567 TI - Significance and evaluation of proteinuria. PMID- 7868568 TI - Hemorheological changes in hypertension: a review. PMID- 7868569 TI - Conradi's disease (dysplasia epiphysalis punctata). PMID- 7868570 TI - Suicide in typhoid fever: a rare neuropsychiatric manifestation of Salmonella infection. PMID- 7868571 TI - Seizures due to food allergy. PMID- 7868572 TI - Hypoglycaemia in aluminium phosphide poisoning. PMID- 7868573 TI - Cyclosporine in pure red cell aplasia. PMID- 7868574 TI - Mention of blood group on driving licences: a genuine addition. PMID- 7868575 TI - Steven-Johnson's syndrome following single dose of ciprofloxacin. PMID- 7868576 TI - Immune thrombocytopenic purpura in pregnancy. PMID- 7868577 TI - Immune thrombocytopenic purpura in pregnancy. PMID- 7868578 TI - Mantoux test and its relevance in the diagnosis of adult tuberculosis disease. PMID- 7868579 TI - Acute renal failure and jaundice in severe falciparum malaria. PMID- 7868580 TI - Double-blind controlled studies. PMID- 7868581 TI - Aluminium phosphide poisoning and magnesium sulphate therapy. PMID- 7868582 TI - Lipoproteins of gram-positive bacteria. PMID- 7868583 TI - Catabolic ornithine transcarbamylase of Halobacterium halobium (salinarium): purification, characterization, sequence determination, and evolution. AB - Halobacterium halobium (salinarium) is able to grow fermentatively via the arginine deiminase pathway, which is mediated by three enzymes and one membrane bound arginine-ornithine antiporter. One of the enzymes, catabolic ornithine transcarbamylase (cOTCase), was purified from fermentatively grown cultures by gel filtration and ammonium sulfate-mediated hydrophobic chromatography. It consists of a single type of subunit with an apparent molecular mass of 41 kDa. As is common for proteins of halophilic Archaea, the cOTCase is unstable below 1 M salt. In contrast to the cOTCase from Pseudomonas aeruginosa, the halophilic enzyme exhibits Michaelis-Menten kinetics with both carbamylphosphate and ornithine as substrates with Km values of 0.4 and 8 mM, respectively. The N terminal sequences of the protein and four peptides were determined, comprising about 30% of the polypeptide. The sequence information was used to clone and sequence the corresponding gene, argB. It codes for a polypeptide of 295 amino acids with a calculated molecular mass of 32 kDa and an amino acid composition which is typical of halophilic proteins. The native molecular mass was determined to be 200 kDa, and therefore the cOTCase is a hexamer of identical subunits. The deduced protein sequence was compared to the cOTCase of P. aeruginosa and 14 anabolic OTCases, and a phylogenetic tree was constructed. The halobacterial cOTCase is more distantly related to the cOTCase than to the anabolic OTCase of P. aeruginosa. It is found in a group with the anabolic OTCases of Bacillus subtilis, P. aeruginosa, and Mycobacterium bovis. PMID- 7868584 TI - Characterization and localization of the KpsE protein of Escherichia coli K5, which is involved in polysaccharide export. AB - In Escherichia coli with group II capsules, the synthesis and cellular expression of capsular polysaccharide are encoded by the kps gene cluster. This gene cluster is composed of three regions. The central region 2 encodes proteins involved in polysaccharide synthesis, and the flanking regions 1 and 3 direct the translocation of the finished polysaccharide across the cytoplasmic membrane and its surface expression. The kps genes of the K5 polysaccharide, which is a group II capsular polysaccharide, have been cloned and sequenced. Region 1 contains the kpsE, -D, -U, -C, and -S genes. In this communication we describe the KpsE protein, the product of the kpsE gene. A truncated kpsE gene was fused with a truncated beta-galactosidase gene to generate a fusion protein containing the first 375 amino acids of beta-galactosidase and amino acids 67 to 382 of KpsE (KpsE'). This fusion protein was isolated and cleaved with factor Xa, and the purified KpsE' was used to immunize rabbits. Intact KpsE was extracted from the membranes of a KpsE-overexpressing recombinant strain with octyl-beta-glucoside. It was purified by affinity chromatography with immobilized anti-KpsE antibodies. Cytofluorometric analysis using the anti-KpsE antibodies with whole cells and spheroplasts, as well as sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting (immunoblotting) of proteins from spheroplasts and membranes before and after treatment with proteinase K, indicated that the KpsE protein is associated with the cytoplasmic membrane and has an exposed periplasmic domain. By TnphoA mutagenesis and by constructing beta lactamase fusions to the KpseE protein, it was possible to determine the topology of the KpsE protein within the cytoplasmic membrane. PMID- 7868585 TI - Characterization of the protein conferring immunity to the antimicrobial peptide carnobacteriocin B2 and expression of carnobacteriocins B2 and BM1. AB - Cloning of a 16-kb DNA fragment from the 61-kb plasmid of Carnobacterium piscicola LV17B into plasmidless C. piscicola LV17C restores the production of the plasmid-encoded carnobacteriocin B2 and the chromosomally-encoded carnobacteriocin BM1 and restores the immune phenotype. This fragment also has sufficient genetic information to allow the expression of carnobacteriocin B2 and its immunity in a heterologous host. The gene locus (cbiB2) responsible for immunity to carnobacteriocin B2 is located downstream of the structural gene for carnobacteriocin B2 and encodes a protein of 111 amino acids (CbiB2). CbiB2 was expressed in Escherichia coli as a fusion of the maltose-binding protein and CbiB2. The fusion protein was purified on an amylose column and cleaved with factor Xa, and pure CbiB2 was isolated by high-performance liquid chromatography. The N-terminal amino acid sequence and mass spectrometry (molecular weight [mean +/- standard error], 12,662.2 +/- 3.4) of the purified protein agree with the information deduced from the nucleotide sequence of cbiB2. Western blot (immunoblot) analysis indicates that the majority of the intracellular pool of this immunity protein is in the cytoplasm and that a smaller proportion is associated with the membrane. CbiB2 confers immunity to carnobacteriocin B2, but not to carnobacteriocin BM1, when it is expressed in homologous or heterologous hosts. No protective effect is observed for sensitive cells growing in the presence of the bacteriocin when the immunity protein is added to the medium. The purified immunity protein does not show significant binding to microtiter plates coated with carnobacteriocin B2 and is not able to inactivate the bacteriocin in solution. PMID- 7868586 TI - Structure of the gluABCD cluster encoding the glutamate uptake system of Corynebacterium glutamicum. AB - To assess the mechanism and function of the glutamate uptake system of gram positive Corynebacterium glutamicum, a mutant deficient in glutamate uptake was isolated and was then used to isolate a DNA fragment restoring this deficiency. In a low-copy-number vector, this fragment resulted in an increased glutamate uptake rate of 4.9 nmol/min/mg (wild type, 1.5 nmol/min/mg). In addition, carbon source-dependent regulation of the glutamate uptake system was determined with the fragment, showing that the entire structures required for expression and control reside on the fragment isolated. Sequencing of 3,977 bp revealed the presence of a four-gene cluster (gluABCD) with deduced polypeptide sequences characteristic of a nucleotide-binding protein (GluA), a periplasmic binding protein (GluB), and integral membrane proteins (GluC and GluD), identifying the glutamate transporter as a binding protein-dependent system (ABC transporter). This identification was confirmed by the kinetic characteristics obtained for cells grown in the presence of globomycin, which exhibited an increased Km of 1,400 microM (without globomycin, the Km was 1.5 microM) but a nearly unaltered maximum velocity. By applying gene-directed mutagenesis, a strain with the entire cluster deleted was constructed. With this mutant, the glutamate uptake rate was reduced from 1.4 to less than 0.1 nmol/min/mg, which is proof that this system is the only relevant one for glutamate uptake. With this strain, the glutamate excretion rate was unaffected (18 nmol/min/mg), showing that no component of gluABCD is involved in export but rather that a specific machinery functions for the latter purpose. PMID- 7868587 TI - Cin-mediated recombination at secondary crossover sites on the Escherichia coli chromosome. AB - The Cin recombinase is known to mediate DNA inversion between two wild-type cix sites flanking genetic determinants for the host range of bacteriophage P1. Cin can also act with low frequency at secondary (or quasi) sites (designated cixQ) that have lower homology to either wild-type site. An inversion tester sequence able to reveal novel operon fusions was integrated into the Escherichia coli chromosome, and the Cin recombinase was provided in trans. Among a total of 13 Cin-mediated inversions studied, three different cixQ sites had been used. In two rearranged chromosomes, the breakpoints of the inversions were mapped to cixQ sites in supB and ompA, representing inversions of 109 and 210 kb, respectively. In the third case, a 2.1-kb inversion was identified at a cixQ site within the integrated sequences. This derivative itself was a substrate for a second inversion of 1.5 kb between the remaining wild-type cix and still another cixQ site, thus resembling a reversion. In analogy to that which is known from DNA inversion on plasmids, homology of secondary cix sites to wild-type recombination sites is not a strict requirement for inversion to occur on the chromosome. The chromosomal rearrangements which resulted from these Cin-mediated inversions were quite stable and suffered no growth disadvantage compared with the noninverted parental strain. The mechanistic implications and evolutionary relevance of these findings are discussed. PMID- 7868588 TI - Transcriptional analysis of the Pseudomonas aeruginosa exoenzyme S structural gene. AB - The transcriptional regulation of the Pseudomonas aeruginosa exoS gene was investigated. Expression of exoS in P. aeruginosa PA103 was dependent upon growth in a low-cation environment and the presence of a functional exsA gene. Promoter fusion analysis indicated that a 285-bp PstI-NsiI fragment, located 5' of the exoS coding region, contained a functional promoter for exoS. Expression of the reporter gene was inducible in a low-cation growth environment and required a functional copy of exsA. Divergent promoters, coordinately regulated with exoS transcription, were identified within the PstI-NsiI fragment. A fusion derivative of ExsA, MALA3A2, was shown to bind directly to the PstI-NsiI probe. DNase I protection analysis demonstrated that MALA3A2 bound to the intergenic region between the postulated -35 boxes of each promoter region. Northern (RNA) blot analysis with probes internal to and upstream of exoS demonstrated that separate, coordinately regulated mRNAs were expressed in P. aeruginosa. These data suggested that a locus, coregulated with exoS transcription, was located upstream of exoS. DNA sequence analysis of the exoS upstream region revealed three open reading frames, ORF 1, ORF 2, and ORF 3. ORF 1 demonstrated significant homology to the SycE/YerA protein of Yersinia sp. SycE/YerA is postulated to function as a chaperone for the YopE cytotoxin. The loci encoding YopE and ExoS show similarities in genetic organization, protein composition, and regulation. PMID- 7868589 TI - Site-directed mutagenesis of histidine residues in Clostridium perfringens alpha toxin. AB - Mutagenesis of H-68 or -148 in Clostridium perfringens alpha-toxin resulted in complete loss of hemolytic, phospholipase C, sphingomyelinase, and lethal activities of the toxin. These activities of the variant toxin at H-126 or -136 decreased by approximately 100-fold of the activities of the wild-type toxin. Mutation at H-46, -207, -212, or -241 showed no effect on the biological activities, indicating that these residues are not essential for these activities. The variant toxin at H-11 was not detected in culture supernatant and in cells of the transformant carrying the variant toxin gene. Wild-type toxin and the variant toxin at H-148 bound to erythrocytes in the presence of Ca2+; however, the variant toxins at H-68, -126, and -136 did not. Co2+ and Mn2+ ions stimulated binding of the variant toxin at H-68, -126, and -136 to membranes in the presence of Ca2+ and caused an increase in hemolytic activity. Wild-type toxin and the variant toxins at H-68, -126, and -136 contained two zinc atoms in the molecule. Wild-type toxin inactivated by EDTA contained two zinc atoms. These results suggest that wild-type toxin contains two tightly bound zinc atoms which are not coordinated to H-68, -126, and -136. The variant toxin at H-148 possessed only one zinc atom. Wild-type toxin and the variant toxin at H-148 showed [65Zn]2+ binding, but the variant toxins at H-68, -126, and -136 did not. Furthermore, [65Zn]2+ binding to wild-type toxin was competitively inhibited by unlabeled Zn2+, Co2+, and Mn2+. These results suggest that H-68, -126, and -136 residues bind an exchangeable and labile metal which is important for binding to membranes and that H-148 tightly binds one zinc atom which is essential for the active site of alpha-toxin. PMID- 7868590 TI - Transcriptional activation of the nitrogenase promoter in vitro: adenosine nucleotides are required for inhibition of NIFA activity by NIFL. AB - The enhancer-binding protein NIFA is required for transcriptional activation of nif promoters by the alternative holoenzyme form of RNA polymerase, which contains the sigma factor sigma 54 (sigma N). NIFA hydrolyzes nucleoside triphosphates to catalyze the isomerization of closed promoter complexes to transcriptionally competent open complexes. The activity of NIFA is antagonized by the regulatory protein NIFL in response to oxygen and fixed nitrogen in vivo. We have investigated the requirement for nucleotides in the formation and stability of open promoter complexes by NIFA and inhibition of its activity by NIFL at the Klebsiella pneumoniae nifH promoter. Open complexes formed by sigma 54-containing RNA polymerase are considerably more stable to heparin challenge in the presence of GTP than in the presence of ATP. This differential stability is most probably a consequence of GTP being the initiating nucleotide at this promoter. Adenosine nucleosides are specifically required for Azotobacter vinelandii NIFL to inhibit open complex formation by native NIFA, and the nucleoside triphosphatase activity of NIFA is strongly inhibited by NIFL under these conditions. We propose a model in which NIFL modulates the activity of NIFA via an adenosine nucleotide switch. PMID- 7868591 TI - Overlapping substrate specificities of benzaldehyde dehydrogenase (the xylC gene product) and 2-hydroxymuconic semialdehyde dehydrogenase (the xylG gene product) encoded by TOL plasmid pWW0 of Pseudomonas putida. AB - Two aldehyde dehydrogenases involved in the degradation of toluene and xylenes, namely, benzaldehyde dehydrogenase and 2-hydroxymuconic semialdehyde dehydrogenase, are encoded by the xylC and xylG genes, respectively, on TOL plasmid pWW0 of Pseudomonas putida. The nucleotide sequence of xylC was determined in this study. A protein exhibiting benzaldehyde dehydrogenase activity had been purified from cells of P. putida (pWW0) (J. P. Shaw and S. Harayama, Eur. J. Biochem. 191:705-714, 1990); however, the amino-terminal sequence of this protein does not correspond to that predicted from the xylC sequence but does correspond to that predicted from the xylG sequence. The protein purified in the earlier work was therefore 2-hydroxymuconic semialdehyde dehydrogenase (the xylG gene product). This conclusion was confirmed by the fact that this protein oxidized 2-hydroxymuconic semialdehyde (kcat/Km = 1.6 x 10(6) s 1 M-1) more efficiently than benzaldehyde (kcat/Km = 3.2 x 10(4) s-1 M-1). The xylC product, the genuine benzaldehyde dehydrogenase, was purified from extracts of P. putida (pWW0-161 delta rylG) which does not synthesize 2-hydroxymuconic semialdehyde dehydrogenase. The amino-terminal sequence of the purified protein corresponds to the amino-terminal sequence deduced from the xylC sequence. This enzyme efficiently oxidized benzaldehyde (kcat/Km = 1.7 x 10(7) s-1 M-1) and its analogs but did not oxidize 2-hydroxymuconic semialdehyde or its analogs. PMID- 7868592 TI - Heterologous expression of an engineered biosynthetic pathway: functional dissection of type II polyketide synthase components in Streptomyces species. AB - Polyketides are an extensive class of secondary metabolites with diverse molecular structures and biological activities. A plasmid-based multicomponent polyketide synthase expression cassette was constructed using a subset of actinorhodin (act) biosynthetic genes (actI-orf1, actI-orf2, actI-orf3, actIII, actVII, and actIV) from Streptomyces coelicolor which specify the construction of the anthraquinone product aloesaponarin II, a molecule derived from acetyl coenzyme A and 7 malonyl coenzyme A extender units. This system was designed as an indicator pathway in Streptomyces parvulus to quantify polyketide product formation and to examine the functional significance of specific polyketide synthase components, including the act beta-ketoacyl synthase (beta-KS; encoded by actI-orf1 and actI-orf2) and the act cyclase/dehydrase (encoded by actVII orf4). Site-directed mutagenesis of the putative active site Cys (to a Gln) in the actI-orf1 beta-KS product completely abrogated aloesaponarin II production. Changing the putative acyltransferase active-site Ser (to a Leu) located in the actI-orf1 beta-KS product led to significantly reduced but continued production of aloesaponarin II. Replacement of the expression cassette with one containing a mutant form of actI-orf2 gave no production of aloesaponarin II or any other detectable polyketide products. However, an expression cassette containing a mutant form of actVII-orf4 gave primarily mutactin with low-level production of aloesaponarin II. PMID- 7868593 TI - Functional characterization and transcriptional analysis of the dnrR1 locus, which controls daunorubicin biosynthesis in Streptomyces peucetius. AB - We previously proposed that the adjacent dnrIJ genes represent a two-component regulatory system controlling daunorubicin biosynthesis in Streptomyces peucetius on the basis of the homology of the DnrI and DnrJ proteins to other response regulator proteins and the effect of a dnrI::aphII mutation. In the present paper we report the results of work with the dnrI::aphII mutant in complementation, bioconversion, and transcriptional analysis experiments to understand the function of dnrI. For five putative operons in the sequenced portion of the S. peucetius daunorubicin biosynthesis gene cluster examined, all of the potential transcripts are present in the delta dnrJ mutant and wild-type strains but absent in the dnrI::aphII strain. Since these transcripts code for both early- and late acting enzymes in daunorubicin biosynthesis, dnrI seems to control all of the daunorubicin biosynthesis genes directly or indirectly. Transcriptional mapping of the 5' and 3' ends of the dnrIJ transcript and the termination site of the convergently transcribed dnrZUV transcript reveals, interestingly, that the two transcripts share extensive complementarity in the regions coding for daunorubicin biosynthesis enzymes. In addition, dnrI may regulate the expression of the drrAB and drrC daunorubicin resistance genes. The delta dnrJ mutant accumulates epsilon-rhodomycinone, the aglycone precursor of daunorubicin. Since this mutant contains transcripts coding for several early- and late-acting enzymes and since dnr mutants blocked in deoxysugar biosynthesis accumulate epsilon-rhodomycinone, we conclude that dnrJ is a daunosamine biosynthesis gene. Moreover, newly available gene sequence data show that the DnrJ protein resembles a group of putative aminotransferase enzymes, suggesting that the role of DnrJ is to add an amino group to an intermediate of daunosamine biosynthesis. PMID- 7868594 TI - Regulation of daunorubicin production in Streptomyces peucetius by the dnrR2 locus. AB - Sequence analysis of the dnrR2 locus from the cluster of daunorubicin biosynthesis genes in Streptomyces peucetius ATCC 29050 has revealed the presence of two divergently transcribed open reading frames, dnrN and dnrO. The dnrN gene appears to encode a response regulator protein on the basis of conservation of the deduced amino acid sequence relative to those of known response regulators and the properties of the dnrN::aphII mutant. Surprisingly, amino acid substitutions (glutamate and asparagine) at the putative site of phosphorylation (aspartate 55) resulted in a reduction rather than a complete loss of DnrN activity. The deduced DnrO protein was found to be similar to the Streptomyces glaucescens tetracenomycin C resistance gene repressor (TcmR) and to two Escherichia coli repressors, the biotin operon repressor (BirA) and the tetracycline resistance gene repressor (TetR). The dnrN::aphII mutation was suppressed by introduction of the dnrI gene on a plasmid. Since the introduction of dnrN failed to restore antibiotic production to a dnrI::aphII mutant, these data suggest the presence of a regulatory cascade in which dnrN activates the transcription of dnrI, which in turn activates transcription of the daunorubicin biosynthesis genes. PMID- 7868595 TI - A manganese-dependent dioxygenase from Arthrobacter globiformis CM-2 belongs to the major extradiol dioxygenase family. AB - Almost all bacterial ring cleavage dioxygenases contain iron as the catalytic metal center. We report here the first available sequence for a manganese dependent 3,4-dihydroxyphenylacetate (3,4-DHPA) 2,3-dioxygenase and its further characterization. This manganese-dependent extradiol dioxygenase from Arthrobacter globiformis CM-2, unlike iron-dependent extradiol dioxygenases, is not inactivated by hydrogen peroxide. Also, ferrous ions, which activate iron extradiol dioxygenases, inhibit 3,4-DHPA 2,3-dioxygenase. The gene encoding 3,4 DHPA 2,3-dioxygenase, mndD, was identified from an A. globiformis CM-2 cosmid library. mndD was subcloned as a 2.0-kb SmaI fragment in pUC18, from which manganese-dependent extradiol dioxygenase activity was expressed at high levels in Escherichia coli. The mndD open reading frame was identified by comparison with the known N-terminal amino acid sequence of purified manganese-dependent 3,4 DHPA 2,3-dioxygenase. Fourteen of 18 amino acids conserved in members of the iron dependent extradiol dioxygenase family are also conserved in the manganese dependent 3,4-DHPA 2,3-dioxygenase (MndD). Thus, MndD belongs to the extradiol family of dioxygenases and may share a common ancestry with the iron-dependent extradiol dioxygenases. We propose the revised consensus primary sequence (G,T,N,R)X(H,A)XXXXXXX(L,I,V,M,F)YXX(D,E,T,N,A)PX(G,P) X(2,3)E for this family. (Numbers in brackets indicate a gap of two or three residues at this point in the sequence.) The suggested common ancestry is also supported by sequence obtained from genes flanking mndD, which share significant sequence identity with xylJ and xylG from Pseudomonas putida. PMID- 7868596 TI - Cloning and characterization of MgtE, a putative new class of Mg2+ transporter from Bacillus firmus OF4. AB - The MM281 strain of Salmonella typhimurium which possesses mutations in each its three known Mg2+ transport systems and requires 100 mM Mg2+ for growth was used to screen a genomic library from the gram-positive alkaliphilic bacterium Bacillus firmus OF4 for clones that could restore the ability to grow without Mg2+ supplementation. Of the clones obtained, five also conferred sensitivity to Co2+, similar to the phenotype of mutants with mutations in the S. typhimurium corA Mg2+ transport locus. All five contained identical inserts by restriction analysis. Using 63Ni2+ as a surrogate for the unavailable 28Mg2+, the plasmid insert was shown to restore cation uptake with properties similar but not identical to those of the S. typhimurium CorA Mg2+ transporter. Sequence analysis of one clone identified a single open reading frame with multiple possible initiation sites. Deletion and mutation analysis identified a minimum open reading frame of 939 bp encoding a polypeptide with a predicted molecular mass of 34 kDa. Disruption of the open reading frame eliminated cation influx activity and restored resistance to Co2+. This putative transporter, designated MgtE, has no sequence similarity to any known protein including CorA and appears to represent a new class of Mg2+ transport system. PMID- 7868597 TI - Structure and regulation of a Candida albicans RP10 gene which encodes an immunogenic protein homologous to Saccharomyces cerevisiae ribosomal protein 10. AB - The Candida albicans clone cDNA10 was isolated on the basis that it encodes a protein which is immunogenic during infections in humans (R. K. Swoboda, G. Bertram, H. Hollander, D. Greenspan, J. S. Greenspan, N. A. R. Gow, G. W. Gooday, and A. J. P. Brown, Infect. Immun. 61:4263-4271, 1993). cDNA10 was used to isolate its cognate gene, and both the cDNA and gene were sequenced, revealing a major open reading frame with the potential to encode a basic protein of 256 amino acids with a predicted molecular weight of 29 kDa. Over its entire length, the open reading frame showed strong homology at both the nucleic acid (75 to 78%) and amino acid (79 to 81%) levels to two Saccharomyces cerevisiae genes encoding the 40S ribosomal protein, Rp10. Therefore, our C. albicans gene was renamed RP10. Northern (RNA) analyses in C. albicans 3153 revealed that RP10 expression is regulated in a manner very similar to that of S. cerevisiae ribosomal genes. The level of the RP10 mRNA decreased upon heat shock (from 25 to 45 degrees C) and was tightly regulated during growth. Maximal levels of the mRNA were reached during mid-exponential phase before they decreased to negligible levels in stationary phase. The level of the RP10 mRNA was induced only transiently during the yeast-to-hyphal morphological transition but did not appear to respond to hyphal development per se. PMID- 7868599 TI - Lipase modulator protein (LimL) of Pseudomonas sp. strain 109. AB - Plasmids containing a Pseudomonas sp. strain 109 extracellular lipase gene (lipL) lacking NH2-terminal sequence and a lipase modulator gene (limL) lacking the NH2 terminal hydrophobic region were constructed and expressed independently in Escherichia coli by using the T7 promoter expression vector system. Recombinant LipL (rLipL) was produced as inclusion bodies, whereas recombinant LimL (rLimL) was present as a soluble protein. During in vitro renaturation of the purified rLipL inclusion bodies after they had been dissolved in 8 M urea, addition of rLimL was essential to solubilize and modulate rLipL. The solubility and activity of rLipL were influenced by the rLimL/rLipL molar ratio; the highest level of solubility was obtained at an rLimL/rLipL ratio of 4:5, whereas the highest activity level was obtained at an rLimL/rLipL ratio of 4:1. After renaturation, rLipL and rLimL were coprecipitated with anti-rLipL antibody, indicating the formation of an rLipL-rLimL complex. Activity of the native lipase purified from Pseudomonas sp. strain 109 was also inhibited by rLimL. By Western blotting (immunoblotting) with anti-rLimL antibody, native LimL was detected in Pseudomonas cells solubilized by sarcosyl treatment. LimL was purified from Pseudomonas sp. strain 109, and the NH2-terminal amino acid sequence was determined to be NH2-Leu-Glu-Pro-Ser-Pro-Ala-Pro-. We propose that to prevent membrane degradation, LimL weakens lipase activity inside the cell, especially in the periplasm, in addition to modulating lipase folding. PMID- 7868598 TI - bor gene of phage lambda, involved in serum resistance, encodes a widely conserved outer membrane lipoprotein. AB - bor is one of two recently identified genes of phage lambda which are expressed during lysogeny and whose products display homology to bacterial virulence proteins. bor is closely related to the iss locus of plasmid CoIV,I-K94, which promotes bacterial resistance to serum complement killing in vitro and virulence in animals. bor has a similar in vitro effect. We show here that the bor gene product is a lipoprotein located in the Escherichia coli outer membrane. We also find that antigenically related proteins are expressed by lysogens of a number of other lambdoid coliphage, in cells carrying the cloned iss gene, and in several clinical isolates of E. coli. These results demonstrate that bor sequences are widespread and present a starting point for mechanistic analysis of bor-mediated serum resistance. PMID- 7868600 TI - A complex network regulates expression of eps and other virulence genes of Pseudomonas solanacearum. AB - We have discovered an unusual and complex regulatory network used by the phytopathogen Pseudomonas solanacearum to control transcription of eps, which encodes for production of its primary virulence factor, the exopolysaccharide EPS I. The major modules of this network were shown to be three separate signal transduction systems: PhcA, a LysR-type transcriptional regulator, an dual two component regulatory systems, VsrA/VsrD and VsrB/VsrC. Using lacZ fusions and RNA analysis, we found that both PhcA and VsrA/VsrD control transcription of another network component, xpsR, which in turn acts in conjunction with vsrB/vsrC to increase transcription of the eps promoter by > 25-fold. Moreover, gel shift DNA binding assays showed that PhcA specifically binds to the xpsR promoter region. Thus, the unique XpsR protein interconnects the three signal transduction systems, forming a network for convergent control of EPS I in simultaneous response to multiple environmental inputs. In addition, we demonstrate that each individual signaling system of the network also acts independently to divergently regulate other unique sets of virulence factors. The purpose of this complex network may be to allow this phytopathogen to both coordinately or independently regulate diverse virulence factors in order to cope with the dynamic situations and conditions encountered during interactions with plants. PMID- 7868601 TI - Alteration of lysine 178 in the hinge region of the Escherichia coli ada protein interferes with activation of ada, but not alkA, transcription. AB - The ada gene of Escherichia coli K-12 encodes the 39-kDa Ada protein, which consists of two domains joined by a hinge region that is sensitive to proteolytic cleavage in vitro. The amino-terminal domain has a DNA methyltransferase activity that repairs the S-diastereoisomer of methylphosphotriesters while the carboxyl terminal domain has a DNA methyltransferase activity that repairs O6 methylguanine and O4-methylthymine lesions. Transfer of a methyl group to Cys-69 by repair of a methylphosphotriester lesion converts Ada into a transcriptional activator of the ada and alkA genes. Activation of ada, but not alkA, requires elements contained within the carboxyl-terminal domain of Ada. In addition, physiologically relevant concentrations of the unmethylated form of Ada specifically inhibit methylated Ada-promoted ada transcription both in vitro and in vivo and it has been suggested that this phenomenon plays a pivotal role in the down-regulation of the adaptive response. A set of site-directed mutations were generated within the hinge region, changing the lysine residue at position 178 to leucine, valine, glycine, tyrosine, arginine, cysteine, proline, and serine. All eight mutant proteins have deficiencies in their ability to activate ada transcription in the presence or absence of a methylating agent but are proficient in alkA activation. AdaK178P (lysine 178 changed to proline) is completely defective for the transcriptional activation function of ada while it is completely proficient for transcriptional activation of alkA. In addition, AdaK178P possesses both classes of DNA repair activities both in vitro and in vivo. Transcriptional activation of ada does not occur if both the amino- and carboxyl-terminal domains are produced separately within the same cell. The mutation at position 178 might interfere with activation of ada transcription by changing a critical contact with RNA polymerase, by causing a conformational change of Ada, or by interfering with the communication of conformational information between the amino- and the carboxyl-terminal domains. These results indicate that the hinge region of Ada is important for ada but not alkA transcription and further support the notion that the mechanism(s) by which Ada activates ada transcription differs from that by which it activates transcription at alkA. PMID- 7868602 TI - Mutational analysis of the redox-sensitive transcriptional regulator OxyR: regions important for oxidation and transcriptional activation. AB - OxyR is a redox-sensitive transcriptional regulator of the LysR family which activates the expression of genes important for the defense against hydrogen peroxide in Escherichia coli and Samonella typhimurium. OxyR is sensitive to oxidation and reduction, and only oxidized OxyR is able to activate transcription of its target genes. Using site-directed mutagenesis, we found that one cysteine residue (C-199) is critical for the redox sensitivity of OxyR, and a C-199-->S mutation appears to lock the OxyR protein in the reduced form. We also used a random mutagenesis approach to isolate eight constitutively active mutants. All of the mutations are located in the C-terminal half of the protein, and four of the mutations map near the critical C-199 residue. In vivo as well as in vitro transcription experiments showed that the constitutive mutant proteins were able to activate transcription under both oxidizing and reducing conditions, and DNase I footprints showed that this activation is due to the ability of the mutant proteins to induce cooperative binding of RNA polymerase. Unexpectedly, RNA polymerase was also found to reciprocally affect OxyR binding. PMID- 7868603 TI - Mutational analysis of the redox-sensitive transcriptional regulator OxyR: regions important for DNA binding and multimerization. AB - OxyR is a LysR-type transcriptional regulator which negatively regulates its own expression and positively regulates the expression of proteins important for the defense against hydrogen peroxide in Escherichia coli and Salmonella typhimurium. Using random mutagenesis, we isolated six nonrepressing OxyR mutants that were impaired in DNA binding. Five of the mutations causing the DNA binding defect mapped near the N-terminal helix-turn-helix motif conserved among the LysR family members, confirming that this region is a DNA binding domain in OxyR. The sixth nonrepressing mutant (with E-225 changed to K [E225K]) was found to be predominantly dimeric, in contrast to the tetrameric wild-type protein, suggesting that a C-terminal region defined by the E225K mutation is involved in multimerization. PMID- 7868604 TI - Formyltetrahydrofolate hydrolase, a regulatory enzyme that functions to balance pools of tetrahydrofolate and one-carbon tetrahydrofolate adducts in Escherichia coli. AB - The enzyme encoded by Escherichia coli purU has been overproduced, purified, and characterized. The enzyme catalyzes the hydrolysis of 10-formyltetrahydrofolate (formyl-FH4) to FH4 and formate. Formyl-FH4 hydrolase thus generates the formate that is used by purT-encoded 5'-phosphoribosylglycinamide transformylase for step three of de novo purine nucleotide synthesis. Formyl-FH4 hydrolase, a hexamer with 32-kDa subunits, is activated by methionine and inhibited by glycine. Heterotropic cooperativity is observed for activation by methionine in the presence of glycine and for inhibition by glycine in the presence of methionine. These results, along with previous mutant analyses, lead to the conclusion formyl FH4 hydrolase is a regulatory enzyme whose main function is to balance the pools of FH4 and C1-FH4 in response to changing growth conditions. The enzyme uses methionine and glycine to sense the pools of C1-FH4 and FH4, respectively. PMID- 7868605 TI - Identification of an iron-regulated outer membrane protein of Neisseria meningitidis involved in the utilization of hemoglobin complexed to haptoglobin. AB - Hemoglobin complexed to the plasma protein haptoglobin can be used by Neisseria meningitidis as a source of iron to support growth in vitro. An N meningitidis mutant, DNM2E4, was generated by insertion of the mini-Tn3erm transposon into the gene coding for an 85-kDa iron-regulated outer membrane protein. Membrane proteins prepared from DNM2E4 were identical to those of the wild-type strain except that the 85-kDa protein was not produced. This mutant was unable to use hemoglobin-haptoglobin complexes as an iron source to support growth and was also impaired in the utilization of free hemoglobin. The mutant failed to bind free hemoglobin, hemoglobin-haptoglobin complexes, or apo-haptoglobin in a solid-phase dot blot assay. The 85-kDa protein was affinity purified when hemoglobin haptoglobin complexes were used as a ligand but was not purified when free hemoglobin was used. We hypothesize that the 85-kDa iron-regulated protein is the hemoglobin-haptoglobin receptor and designate this protein Hpu (for hemoglobin haptoglobin utilization). PMID- 7868606 TI - Functional analysis of the gene encoding the clavaminate synthase 2 isoenzyme involved in clavulanic acid biosynthesis in Streptomyces clavuligerus. AB - A Streptomyces clavuligerus mutant disrupted in cas2, encoding the clavaminate synthase (CAS2) isoenzyme, was constructed by a gene replacement procedure. The resulting cas2 mutant showed no clavulanic acid production when grown in starch asparagine medium. However, in soy medium, the cas2 mutant did produce clavulanic acid, although in amounts less than those produced by wild-type cultures. This medium-dependent leaky phenotype correlated well with the presence of the cas1 transcript, encoding the CAS1 isoenzyme, in cultures grown in soy medium and with its absence from those grown in starch-asparagine medium. This suggested that CAS1 and CAS2 both contribute to clavulanic acid production but that their production is regulated differently. Under nutritional conditions in which cas1 expression is blocked, cas2 becomes essential for clavulanic acid production. Northern (RNA) analysis revealed that while cas1 is transcribed as a 1.4-kb monocistronic transcript only, cas2 is transcribed both as a 1.2-kb monocistronic transcript and as part of a 5.3-kb polycistronic transcript. High-resolution S1 nuclease analysis located the transcription start point of the monocistronic cas2 transcript at a C residue 103 nucleotides upstream from the cas2 start codon. PMID- 7868607 TI - Roles of the three transcriptional attenuators of the Bacillus subtilis pyrimidine biosynthetic operon in the regulation of its expression. AB - Expression of the Bacillus subtilis pyr operon is regulated by exogenous pyrimidines and the protein product of the first gene of the operon, PyrR. It has been proposed that PyrR mediates transcriptional attenuation at three untranslated segments of the operon (R.J. Turner, Y. Lu, and R.L. Switzer, J. Bacteriol., 176:3708-3722, 1994). In this study, transcriptional fusions of the pyr promoter followed by the pyr attenuation sequences, either individually or in tandem to a lacZ reporter gene, were used to examine the physiological functions of all three attenuators through their ability to affect beta-galactosidase expression. These fusions were studied as chromosomal integrants in various B. subtilis strains to examine the entire range of control by pyrimidines, PyrR dependence, amd developmental control of pyr gene expression. The nutritional regulation of each attenuator separately was roughly equivalent to that of the other two and was totally dependent upon PyrR, and that of tandem attenuators was cumulative. The regulation of a fusion of the spac promoter followed by the pyrP:pyrB intercistronic region to lacZ produced results similar to those obtained with the corresponding fusion containing the pyr promoter, demonstrating that attenuator-dependent regulation is independent of the promoter. Extreme pyrimidine starvation gave rise to two- to threefold-higher levels of expression of a pyr-lacZ fusion that lacked attenuators, independent of PyrR, than were obtained with cells that were not starved. Increased expression of a similar spac lacZ fusion during pyrimidine starvation was also observed, however, indicating that attenuator-independent regulation is not a specific property of the pyr operon. Conversion of the initiator AUG codon in a small open reading frame in the pyrP:pyrB intercistronic region to UAG reduced expression by about half but did not alter regulation by pyrimidines, which excludes the possibility of a coupled transcription-translation attenuation mechanism. Developmental regulation of pyr expression during early stationary phase was found to be dependent upon the attenuators and PyrR, and the participation of SpoOA was excluded. PMID- 7868608 TI - DNA helicases in recombination and repair: construction of a delta uvrD delta helD delta recQ mutant deficient in recombination and repair. AB - DNA helicases play pivotal roles in homologous recombination and recombinational DNA repair. They are involved in both the generation of recombinogenic single stranded DNA ends and branch migration of synapsed Holliday junctions. Escherichia coli helicases II (uvrD), IV (helD), and RecQ (recQ) have all been implicated in the presynaptic stage of recombination in the RecF pathway. To probe for functional redundancy among these helicases, mutant strains containing single, double, and triple deletions in the helD, uvrD, and recQ genes were constructed and examined for conjugational recombination efficiency and DNA repair proficiency. We were unable to construct a strain harboring a delta recQ delta uvrD double deletion in a recBC sbcB(C) background (RecF pathway), suggesting that a delta recQ deletion mutation was lethal to the cell in a recBC sbcB(C) delta D background. However, we were able to construct a triple delta recQ delta uvrD Delta helD mutant in the recBC sbcB(C) background. This may be due to the increased mutator frequency in delta uvrD mutants which may have resulted in the fortuitous accumulation of a suppressor mutation(s). The triple helicase mutant recBC sbcB(C) delta uvrD delta recQ delta helD severely deficient in Hfr-mediated conjugational recombination and in the repair of methylmethane sulfonate-induced DNA damage. This suggests that the presence of at least one helicase--helicase II, RecQ helicase, or helicase IV--is essential for homologous recombination and recombinational DNA repair in a recBC sbcB(C) background. The triple helicase mutant was recombination and repair proficient in a rec+ background. Genetic analysis of the various double mutants unmasked additional functional redundancies with regard to conjugational recombination and DNA repair, suggesting that mechanisms of recombination depend both on the DNA substrates and on the genotype of the cell. PMID- 7868609 TI - Spontaneous mutations in pcaH and -G, structural genes for protocatechuate 3,4 dioxygenase in Acinetobacter calcoaceticus. AB - Bacteria containing spontaneous null mutations in pcaH and -G, structural genes for protocatechuate 3,4-dioxygenase, were selected by exposure of an Acinetobacter calcoaceticus strain to physiological conditions in which expression of the genes prevents growth. The parental bacterial strain exhibits high competence for natural transformation, and this procedure was used to characterize 94 independently isolated spontaneous mutations. Four of the mutations were caused by integration of a newly identified insertion sequence, IS1236. Many (22 of 94) of the mutations were lengthy deletions, the largest of which appeared to eliminate at least 17 kb of DNA containing most of the pca-qui pob supraoperonic gene cluster. DNA sequence determination revealed that the endpoints of four smaller deletions (74 to 440 bp in length) contained DNA sequence repetitions aligned imprecisely with the sites of mutation. Analysis of direct and inverted DNA sequence repetitions associated with the sites of mutation suggested the existence of DNA slippage structures that make unhybridized nucleotides particularly susceptible to mutation. PMID- 7868610 TI - Adaptation of Xanthobacter autotrophicus GJ10 to bromoacetate due to activation and mobilization of the haloacetate dehalogenase gene by insertion element IS1247. AB - Monobromoacetate (MBA) is toxic for the 1,2-dichloroethane-degrading bacterium Xanthobacter autotrophicus GJ10 at concentrations higher than 5 mM. Mutants which are able to grow on higher concentrations of MBA were isolated and found to overexpress haloacid dehalogenase, which is encoded by the dhlB gene. In mutant GJ10M50, a DNA fragment (designated IS1247) had copied itself from a position on the chromosome that was not linked to the dhlB region to a site immediately upstream of dhlB, resulting in a 1,672-bp insertion. IS1247 was found to encode an open reading frame corresponding to 464 amino acids which showed similarity to putative transposases from two other insertion elements. In most of the other MBA resistant mutants of GJ10, IS1247 was also present in one more copy than in the wild type, which had two copies located within 20 kb. After insertion to a site proximal to dhlB, IS1247 was able to transpose itself together with the dhlB gene to a plasmid, without the requirement of a second insertion element being present downstream of dhlB. The results show that IS1247 causes bromoacetate resistance by overexpression and mobilization of the haloacid dehalogenase gene, which mimics steps during the evolution of a catabolic transposon and plasmid during adaptation to a toxic growth substrate. PMID- 7868611 TI - Ethanolamine utilization in Salmonella typhimurium: nucleotide sequence, protein expression, and mutational analysis of the cchA cchB eutE eutJ eutG eutH gene cluster. AB - A fragment of the Salmonella typhimurium ethanolamine utilization operon was cloned and characterized. The 6.3-kb nucleotide sequence encoded six complete open reading frames, termed cchA, cchB, eutE, eutJ, eutG, and eutH. In addition, the nucleotide sequences of two incomplete open reading frames, termed eutX and eutI, were also determined. Comparison of the deduced amino acid sequences and entries in the GenBank database indicated that eutI encodes a phosphate acetyltransferase-like enzyme. The deduced amino acid sequences of the EutE and EutG proteins revealed a significant degree of homology with the Escherichia coli alcohol dehydrogenase AdhE sequence. Mutations in eutE or eutG completely abolished the ability of mutants to utilize ethanolamine as a carbon source and reduced the ability to utilize ethanolamine as a nitrogen source. The product of eutE is most probably an acetaldehyde dehydrogenase catalyzing the conversion of acetaldehyde into acetyl coenzyme A. The product of the eutG gene, an uncommon iron-containing alcohol dehydrogenase, may protect the cell from unconverted acetaldehyde by converting it into an alcohol. The deduced amino acid sequence of cchA resembles that of carboxysome shell proteins from Thiobacillus neapolitanus and Synechococcus sp. as well as that of the PduA product from S. typhimurium. CchA and CchB proteins may be involved in the formation of an intracellular microcompartment responsible for the metabolism of ethanolamine. The hydrophobic protein encoded by the eutH gene possesses some characteristics of bacterial permeases and might therefore be involved in the transport of ethanolamine. Ethanolamine-utilization mutants were slightly attenuated in a mouse model of S. typhimurium infection, indicating that ethanolamine may be an important source of nitrogen and carbon for S. typhimurium in vivo. PMID- 7868612 TI - Activity of the Agrobacterium Ti plasmid conjugal transfer regulator TraR is inhibited by the product of the traM gene. AB - The Agrobacterium Ti plasmid tra regulon was previously found to be positively regulated by the TraR protein in the presence of a diffusible N-acyl homoserine lactone designated Agrobacterium autoinducer (AAI). TraR and AAI are similar to LuxR from Vibrio fischeri and the Vibrio autoinducer (VAI), which regulate target bioluminescence (lux) genes in a cell density-dependent manner. We now show that tra genes are also regulated by a second protein, designated TraM, which acts to antagonize TraR-dependent activation. The traM gene is closely linked to traR, and the two genes are transcribed convergently. The predicted TraM proteins of two different Ti plasmids are 77% identical but are not significantly similar to other protein sequences in the database, and thus TraM may represent a novel regulatory protein. Null mutations in traM cause strongly increased conjugation, tra gene transcription, and AAI production. A functional copy of traM introduced into traM mutants decreased conjugation, tra gene transcription, and AAI synthesis. TraM inhibits transcription of traA, traI, and traM. Although traM was first identified by its octopine-inducible promoter, we now show that induction by octopine requires traR, strongly suggesting that TraR is the direct traM activator. PMID- 7868614 TI - Strain-dependent variation in carbon source regulation of nucleus-encoded mitochondrial proteins of Saccharomyces cerevisiae. AB - Nuclear genes encoding mitochondrial proteins are regulated by carbon source with significant heterogeneity among four Saccharomyces cerevisiae strains. This strain-dependent variation is seen both in respiratory capacity of the cells and in the expression of beta-galactosidase reporter fusions to the promoters of CYB2, CYC1, CYC3, MnSOD, and RPO41. PMID- 7868613 TI - Heat shock-dependent transcriptional activation of the metA gene of Escherichia coli. AB - In Escherichia coli, the growth rate at elevated temperatures is controlled by the availability of endogenous methionine, which is limited because of the temperature sensitivity of the metA gene product, homoserine transsuccinylase (HTS). In order to determine the relationship between this control mechanism and the heat shock response, we estimated the cellular levels of HTS during heat shock by Western (immunoblot) analysis and found an increase following induction by temperature shift and by addition of ethanol or cadmium ions. The elevated level of HTS was a result of transcriptional activation of the metA gene. This activation was heat shock dependent, as it did not take place in rpoH mutants, and probably specific to the metA gene, as another gene of the methionine regulon (metE) was not activated. These results suggest a metabolic link between the two systems that control the response of E. coli to elevated temperatures: the metA gene, which codes for the enzyme responsible for regulating cell growth as a function of temperature elevation (HTS), is transcriptionally activated by the heat shock response. PMID- 7868615 TI - MudSacI, a transposon with strong selectable and counterselectable markers: use for rapid mapping of chromosomal mutations in Salmonella typhimurium. AB - The transposable bacteriophage Mu and its mini-Mu derivatives are useful tools for the genetic analysis of many bacteria. A variety of antibiotic-resistant Mu derivatives have been constructed, allowing direct selection for cells which contain the transposon. However, in many cases a counterselection against the transposon would greatly facilitate further genetic analysis. In this paper we report the construction of MudSacI, a mini-Mu derived transposon containing the sacB (secretory levansucrase) gene of Bacillus subtilis, which confers sucrose sensitivity upon gram-negative bacteria. We describe the use of this transposon as a tool for rapid genetic mapping of chromosomal genes in Salmonella typhimurium. Simple modifications of this approach should facilitate rapid mapping in many other bacteria as well. PMID- 7868616 TI - Escherichia coli NusG protein stimulates transcription elongation rates in vivo and in vitro. AB - The rate of transcription elongation in Escherichia coli was reduced when cells were depleted of NusG. In a purified in vitro system, NusG accelerated the transcription elongation rate. The stimulation of the rate of transcription elongation by NusG appears to result from the suppression of specific transcription pause sites. PMID- 7868617 TI - Reshuffling of Rhs components to create a new element. AB - RhsF has been identified as the fourth member of the RhsABCF subfamily of genetic elements. This new element is found in Escherichia coli ECOR-50 and several other strains but not in strain K-12. A novel feature of RhsF is that it represents a new arrangement of components previously uniquely associated with RhsA and RhsC of strain K-12. PMID- 7868618 TI - Subinhibitory concentrations of antibiotics affect cell surface properties of Streptococcus sobrinus. AB - Several antibiotics, at subinhibitory concentrations, caused an increase in the ability of Streptococcus sobrinus to bind alpha-1,6-glucans, whereas other antibiotics decreased glucan binding. In every case, glucan binding was inversely proportional to cell surface hydrophobicity. High levels of glucan-binding activity resulted in low levels of hydrophobicity, whereas low levels of glucan binding caused high levels of cellular hydrophobicity. The results show that low concentrations of antibiotics may modulate lectin and hydrophobin adhesins in streptococci. PMID- 7868619 TI - Accurate determination of the molecular weight of the major surface layer protein isolated from Clostridium thermosaccharolyticum by time-of-flight mass spectrometry. AB - Matrix-assisted laser desorption with concomitant ionization, in combination with a linear time-of-flight mass spectrometer, was used to analyze underivatized and hard-to-solubilize surface layer proteins and glycoproteins by depositing them on top of a microcrystalline layer of the matrix alpha-cyano-4-hydroxycinnamic acid. Use of this special sample preparation technique allowed the first successful desorption-ionization of intact surface layer proteins and accurate determination of their molecular weights by mass spectrometry. The molecular mass of the monomeric subunit of the major surface layer protein isolated from Clostridium thermosaccharolyticum E207-71 was determined to be 75,621 +/- 81 Da. The obtainable mass accuracy of the technique is conservatively considered to be within +/- 0.2%. This result deviates from that given by sodium dodecyl sulfate polyacrylamide gel electrophoresis by approximately 7.4 kDa because this method is strongly affected and biased by the three-dimensional structure of this type of surface protein. With the apparent advantages of unsurpassed mass accuracy, low dependence on the physicochemical properties of the surface layer proteins, and high sensitivity, it can be concluded that a linear time-of-flight instrument combined with UV matrix-assisted laser desorption with concomitant ionization is better suited for molecular weight determination than is gel electrophoresis. PMID- 7868620 TI - Genomic stability in the archaeae Haloferax volcanii and Haloferax mediterranei. AB - Through hybridization of available probes, we have added nine genes to the macrorestriction map of the Haloferax mediterranei chromosome and five genes to the contig map of Haloferax volcanii. Additionally, we hybridized 17 of the mapped cosmid clones from H. volcanii to the H. mediterranei genome. The resulting 35-point chromosomal comparison revealed only two inversions and a few translocations. Forces known to promote rearrangement, common in the haloarchaea, have been ineffective in changing global gene order throughout the nearly 10(7) years of these species' divergent evolution. PMID- 7868623 TI - Principles of arthroscopy and wrist arthroscopy equipment. AB - This article provides an overview of the history of wrist arthroscopy. Following this, the basic principles of wrist arthroscopy are presented. In the final portion of the chapter, the equipment and instrumentation used in wrist arthroscopy are discussed, including traction apparati, arthroscopes, mechanical infusion systems, hand instruments, and shavers. PMID- 7868622 TI - Remarkable N2-fixing bacterial diversity detected in rice roots by molecular evolutionary analysis of nifH gene sequences. AB - To demonstrate the extent of phylogenetic diversity of diazotrophic bacteria associated with rice roots, we characterized phylogenetically 23 nifH gene sequences obtained by PCR amplification of mixed organism DNA extracted directly from rice roots without culturing the organisms. The analyses document the presence of eight novel NifH types, which appear to be a variety of significant components of the diazotrophic community, dominated mainly by proteobacteria. PMID- 7868621 TI - The nasB operon and nasA gene are required for nitrate/nitrite assimilation in Bacillus subtilis. AB - Bacillus subtilis can use either nitrate or nitrite as a sole source of nitrogen. The isolation of the nasABCDEF genes of B. subtilis, which are required for nitrate/nitrite assimilation, is reported. The probable gene products include subunits of nitrate/nitrite reductases and an enzyme involved in the synthesis of siroheme, a cofactor for nitrite reductase. PMID- 7868624 TI - Radiocarpal arthroscopy portals and normal anatomy. AB - Wrist arthroscopy is now an accepted technique in the evaluation of radiocarpal intra-articular pathology. An understanding of the surface anatomic landmarks and articular anatomy is required to safely and effectively perform the technique. Multiple portals are used to arthroscopically view the radiocarpal joint and provide access for irrigation and surgical instruments. PMID- 7868625 TI - Midcarpal arthroscopy: anatomy and portals. AB - Arthroscopy of the midcarpal joint of the wrist is a relatively new procedure made possible by the advances and miniaturization of arthroscopic instrumentation. Only recently has even the basic variability in the normal anatomy of the midcarpal joint been delineated. Midcarpal arthroscopy is becoming a routine part of a complete diagnostic wrist arthroscopy and is offering good views of midcarpal anatomy and new opportunities for arthroscopic treatment of midcarpal and proximal wrist joint traumatic and degenerative pathology. PMID- 7868626 TI - Arthroscopy of the distal radioulnar joint. Indications, portals, and anatomy. AB - Carpal tunnel syndrome is defined as a clinical condition related to dysfunction of the median nerve specifically related to the carpal tunnel. This article reviews anatomy, current surgical treatment options, technique, indications and contraindications, efficacy, complications, and the author's own perspective on the subject. PMID- 7868627 TI - Use of arthroscopy in the evaluation and treatment of chronic wrist pain. AB - Chronic wrist pain can be frustrating for the hand surgeon. The most critical portion of the evaluation is the history and physical examination, which will lead to the various diagnostic modalities available. Table 2 is a summary of some of the more common tests and their uses. Wrist arthroscopy is one of the more useful tools available to the hand surgeon, being both diagnostic and therapeutic. The algorithms developed in this paper are by no means exhaustive or all encompassing. Rather they should be viewed as a guide to assist the hand surgeon in the treatment of these difficult problems. PMID- 7868628 TI - The role of arthroscopy in the treatment of traumatic triangular fibrocartilage injuries. AB - The triangular fibrocartilage complex is a complex anatomic structure located at the ulnar aspect of the wrist and is important to the stability and biomechanical function of the ulnar carpus and distal radioulnar joint. This article will review the anatomy and biomechanical function of the TFCC and its relationship to the diagnosis and treatment of traumatic injuries to the TFCC. PMID- 7868629 TI - Arthroscopic treatment of degenerative tears of the triangular fibrocartilage. AB - The arthroscope permits treatment of degenerative tears of the TFC and associated lesions. It lends itself to the assessment and treatment of both "primary" and "secondary" ulnar impaction syndromes. Ulnocarpal, radiocarpal, and midcarpal synovitis can be excised, as can partial tears of the lunatotriquetral interosseous ligament. The primum movens of the ulnar impaction syndrome, a long ulna, can be shortened arthroscopically if the positive ulnar variance is less than 4 mm and no distal radioulnar joint instability or degenerative changes are noted. Although an arthroscopic "wafer" procedure is possible, more clinical studies are needed to allow an accurate assessment of its efficacy. PMID- 7868630 TI - Endoscopic carpal tunnel release. A current perspective. AB - Carpal tunnel syndrome is defined as a clinical condition related to dysfunction of the median nerve specifically related to the carpal tunnel. This article reviews anatomy, current surgical treatment options, technique, indications and contraindications, efficacy, complications, and the author's own perspective on the subject. PMID- 7868631 TI - Endoscopic carpal tunnel release. Two-portal technique. AB - The historical perspective, indications and contraindications, operating room setup and operative technique, and the ligament cutting technique for the two portal endoscopic carpal ligament release is outline in this article, as well as the potential complications and how to avoid them. The clinical results of 815 patients (1154 wrists) are described. PMID- 7868632 TI - Endoscopic carpal tunnel release using the single proximal incision technique. AB - The goal of the single incision endoscopic technique is to avoid an incision on the palmar surface of the hand. As compared with open release and the two-portal endoscopic technique for release of the carpal tunnel, this single incision technique permits the patient to return earlier to work and activities of daily living as a result of less tenderness and earlier return of strength. Safe performance of the technique requires that the surgeon have both a thorough knowledge of the anatomy of the hand and a commitment to master the technical details of the surgical approach. Because the technique is of value strictly to view and divide the TCL, patient selection requires careful preoperative evaluation to exclude those carpal tunnels with pathology that requires direct inspection or surgical treatment. In a prospective study with the redesigned point of entry blade assembly that allows a view of the blade's entry into the ligament, no device-related complications occurred. In considering a surgical approach for endoscopic carpal tunnel release, the authors feel that it is important to recognize the value of an "open" proximal surgical incision designed to directly view the plane between the finger flexor synovium and the deep surface of the TCL. Stab wound "portals" that are widely used in arthroscopic surgery are inadequate for endoscopic carpal tunnel releases. The device and the procedure are designed to obtain an unobstructed view of the underside of the TCL and divide it completely. Additional long-term prospective studies are needed to define the comparative recurrence rates of open versus single incision endoscopic carpal tunnel release surgeries. PMID- 7868633 TI - Annotation: childhood-onset schizophrenia. PMID- 7868634 TI - Making sense of chronic disease. The eleventh Jack Tizard Memorial Lecture. AB - Three phases in psychosocial research for children with cancer are identified. These phases reflect changing fashions in theoretical perspective and determine the questions asked and the way in which professionals and families "make sense" of the disease experience. First, (1950s and 1960s) information about cancer was not shared with children and families were prepared for the inevitability of death. Second, (1970s and 1980s), the focus shifted from "dying" to "living" with a life-threatening condition. Information became more open. Currently, there is still greater emphasis on "living" with cancer. Attention has also shifted to the psychological needs of the long-term survivor. PMID- 7868635 TI - Determinants of reliability in psychiatric surveys of children aged 6-12. AB - The reliability of young children's self reports of psychiatric information is a concern of epidemiologists and clinicians alike. This paper explores the determinants of test-retest reliability in a sample of children from the general population using reliability coefficients constructed from a kappa statistic. Age, cognitive ability, and gender are related to consistency of reports in a test-retest paradigm. Controlling for age, cognitive ability and gender, children report more reliably on observable behaviors, and less reliably on questions involving unspecified time, reflections of one's own thoughts, and comparison of themselves with others. The reliability of reports of emotions lies between these two extremes. Surprisingly, sentence length of up to 40 words and psychiatric impairment of the child as measured by the Child Global Assessment Scale did not influence reliability. As might be expected, parents' reports of their children are more reliable than their children's reports. PMID- 7868636 TI - An empirical comparison between the DSM and psychodynamic approaches for assessment of child disorders in children attending outpatient clinics. AB - The DSM and psychodynamic approaches provide different perspectives on child psychiatric diagnoses. Taking advantage of the recent publication of a psychodynamically oriented classification of child disorders, correspondences between these approaches were studied in a sample of outpatient clinic children. Clinician judges and a psychiatric interview schedule provided for diagnoses. Classifications of child psychopathology are still imperfect to a large extent. As a result, statistical comparisons can only yield limited relationships and caution is necessary when using classification tools. Methodological difficulties notwithstanding, various associations showed that DSM and psychodynamic constructs, while different, are not entirely independent. PMID- 7868637 TI - Childhood Experience of Care and Abuse (CECA): a retrospective interview measure. AB - The development of a retrospective, investigator-based interview measure of Childhood Experience of Care and Abuse (CECA) used with two community samples of adults in London is described. The component ratings are shown to have satisfactory inter-rater reliability and also validity as determined by agreement between sisters' independent accounts. The association between the different childhood scales is explored as well as the relationship of childhood experiences to adult depression. Methodological issues concerning investigator-based versus respondent-based measures of childhood are discussed and a case made for use of the former. Advantages of using the CECA, a retrospective, time-based measure of childhood, are outlined. PMID- 7868638 TI - An ethological study on behavioural differences between hyperactive, aggressive, combined hyperactive/aggressive and control children. AB - Frequencies and sequential patterns of behaviour elements in pure hyperactive (N = 12), pure aggressive (N = 13), combined hyperactive/aggressive (N = 15) and control children (N = 10) were recorded in a semistructured playroom session and subsequently compared. The samples were age- and IQ-matched. In an overall MANOVA a significant main effect for hyperactivity but not for aggression was found. The hyperactive children were characterized particularly by differences in squirming and changes in sitting. The sequential patterning of their behaviour revealed weaker temporal contingencies between their behaviour and the conversational speech of the experimenter than in the case of the nonhyperactive (aggressive and control) children. This may be explained by deficits in social attention in the hyperactive groups. PMID- 7868639 TI - Children's perceptions of relationships with siblings, friends, and mothers: compensatory processes and links with adjustment. AB - Links between children's psychological adjustment and individual differences in their perceptions of relationships with siblings, mothers, and friends were studied in a sample of 85 second-graders. Results indicated that characteristics of these relationships were significantly correlated with children's loneliness, depressive mood, self-esteem, and behavioral conduct. There were some links among children's perceptions of their relationships with siblings, friends, and mothers. A compensatory model of associations among adjustment and warmth in children's relationships with friends and mothers was supported. Children who reported that their relationships with either mothers, friends, or mothers and friends were characterized by high levels of warmth had significantly better adjustment outcomes than children who reported low levels of warmth in relationships with both friends and mothers. The importance of the network of children's relationships for their mental health is discussed. PMID- 7868640 TI - Wechsler IQ profile and theory of mind in autism: a research note. AB - The unusually uneven intelligence test profile found in autism has been consistently replicated. However, few psychological theories of autism give prominence to this feature. Nor is it clear how currently influential theories, such as the theory of mind account or the executive function hypothesis, can explain the marked peaks and troughs found in the performance of both high- and low-functioning individuals with autism. The present study reports the pattern of Wechsler subtest results for subjects with autism who do or do not pass standard theory of mind tasks. The results suggest that while difficulty with the Comprehension subtest may reflect poor theory of mind, relative skill on the Block Design subtest is characteristic of subjects with autism regardless of theory of mind performance. Implications of this finding for the central coherence hypothesis are considered. PMID- 7868641 TI - Executive function deficits and the pretend play of children with autism: a research note. AB - The failure to produce pretend play seen in autism may arise from executive deficits associated with the syndrome. This experiment investigated the ability of children with autism to use various objects in pretence, the prediction being that they would have particular difficulty using props with a clear function (e.g. a pencil) to perform a different pretend function (e.g. to act as a toothbrush). However, children with autism were as likely as controls to select a prop with an inappropriate function from amongst other, nonfunctional props, suggesting that executive deficits of this particular kind cannot readily explain an absence of pretend play in autism. PMID- 7868642 TI - A modified version of the Rutter parent questionnaire including extra items on children's strengths: a research note. AB - An expanded version of the Rutter parent questionnaire was administered to 320 schoolchildren with hemiplegia. Scores and caseness categories derived from the original Rutter items corresponded well with the findings of independent psychiatric evaluations. A measure of prosocial behaviour derived from 10 novel items had promising internal consistency, factorial independence and inter-rater reliability. Another six novel items loaded on the same factor as the three original Rutter hyperactivity items. The modified questionnaire may be useful with a wide range of children, particularly if the focus on children's strengths as well as weaknesses increases parental compliance and reduces halo effects. PMID- 7868643 TI - An HIV-1 protease screening assay using a non-infectious proviral clone. AB - An in-vitro assay was developed to screen for HIV-1 protease inhibitors using a non-infectious proviral clone (X19) with a deletion in the envelope gene (Ratner et al., 1991). The proviral clone, X19, was expressed transiently in the COS 7 cell line. The virus was able to replicate as assessed by the presence of p24 in the supernatants, yet the virions produced did not infect CD4 positive cells. To determine the effect of a known protease inhibitor on p24 antigen production, PD 148310 (a Ro 31-8959 analog) was added immediately after transfection of the COS 7 cells. Virus particles were produced maximally after 24 h and cell supernatants were assayed for p24 antigen production using a p24 ELISA assay. PD 148310 inhibited p24 release in a dose-dependent manner with an IC50 of 23.6 nM. Western blot analysis of the supernatants using a mouse monoclonal antibody against p24 confirmed the presence of a well-defined p24 band in the control lane. At 1000 nM of PD 148310 the p24 band was not detectable, leaving only the unprocessed p55 Gag precursor. This technique is a useful tool to screen for potential HIV-1 protease inhibitors. PMID- 7868644 TI - Production of measles nucleoprotein in different expression systems and its use as a diagnostic reagent. AB - Measles nucleoprotein has been successfully expressed in three different hosts, bacterial (Escherichia coli BL21 DE3), insect (Spodoptera frugiperda; Sf9) and mammalian (primary human fibroblasts) cells, each producing an antigenic protein of M(r) 60 kDa. The nucleoprotein produced in all three hosts was used in an ELISA for the detection of antibodies to measles virus in a cohort of haemagglutinin-positive or -negative human sera. Data produced from baculovirus and adenovirus-based antigens indicated that there was good correlation between the ELISA results and previous haemagglutination inhibition test data, and there was little background interference by cellular proteins or the development of false positive or negative results. The assay was rapid as it could be carried out in under 4 h, sensitive as the sera could be diluted by at least 1000-fold, and versatile as both IgG and IgM could be detected and differentiated. PMID- 7868645 TI - Inverse polymerase chain reaction for cloning cellular sequences adjacent to integrated hepatitis B virus DNA in hepatocellular carcinomas. AB - Integration of hepatitis B virus (HBV) DNA is found in most HBV-related human hepatocellular carcinomas (HCCs). In the past, construction of genomic libraries was mainly employed to study the role of viral integration. However, large amounts of tissue DNA and a laborious screening procedures were required. Inverse polymerase chain reaction (IPCR) is based on the simple procedures of digestion of DNA with restriction enzymes and circularization of cleavage products before amplification using primers synthesized in the opposite orientations to those normally employed for PCR. This technique allows the in vitro amplification of DNA flanking a region of known sequence. By employing this method, starting from nanograms of hepatoma DNA, two adjacent cellular sequences were cloned from 11 HBV integrants in three HCCs. The original configurations in the chromosomes were further confirmed. One of the flanking cellular sequences was identified as the human 28S rRNA gene, the other was not found homologous to any known human sequences. This method appears to be practical and can be improved further to clone more flanking cellular sequences, especially in early and small HCCs. PMID- 7868646 TI - Use of a recombinant antigen in an indirect ELISA for detecting bovine antibody to capripoxvirus. AB - The gene coding for the capripoxvirus structural protein P32 was cloned, expressed in Escherichia coli as a fusion protein with glutathione-S-transferase, and purified on glutathione Sepharose. An indirect enzyme linked immunosorbent assay (ELISA) using this antigen was developed to screen bovine sera for antibodies to capripoxvirus. Sequential serum samples from experimentally infected animals tested by ELISA and by virus neutralisation test (VNT) showed that the ELISA was more sensitive and detected antibodies to capripoxvirus earlier post-infection than the VNT. PMID- 7868647 TI - Simple and rapid preparation of infected plant tissue extracts for PCR amplification of virus, viroid, and MLO nucleic acids. AB - A rapid, simple method for preparing plant tissues infected with viruses, viroids, or MLOs using a commercial product known as Gene Releaser is described. The Gene Releaser polymeric matrix method produced plant extracts suitable for PCR amplification without the use of organic solvents, ethanol precipitation, or additional nucleic acid purification techniques. Modification of maceration methods and/or extraction buffers resulted in the PCR amplification of potato spindle tuber, apple scar skin, and dapple apple viroids, as well as, genomic segments of plum pox potyvirus, grapevine virus B, grapevine leafroll-associated virus III, and elm yellows MLO. These pathogens were amplified from tissue of woody and herbaceous hosts such as peach, apricot, apple, grapevine, elm, periwinkle and potato. The application of this product for use with intractable tissue avoids lengthy and laborious extraction procedures. In our hands, about 20 samples could be prepared for PCR or RT-PCR in 1-2 h versus 1-3 days. PMID- 7868648 TI - Cryosubstitution technique reveals new morphology of flavivirus-induced structures. AB - Cryotechniques in combination with electron microscopy were used in an attempt to obtain more precise morphological details of flavivirus-induced structures. From conventional chemical fixation procedure, proliferation of endoplasmic reticulum, formation of microtubule paracrystals and clusters of smooth membrane vesicles (with 'thread-like' enclosures) were observed. These induced changes are typical for flavivirus infections. The images obtained from cryosections were disappointing as the structures were not well preserved. On the other hand, cryosubstituted-infected cells gave revealing images of the virus-induced structures. The most obvious difference between the cryosubstituted and chemical fixed processes was on the morphology of the 'thread-like' structure. The 'thread like' structures instead appeared as dense cores. The morphology of the virus particles was also better defined. The envelope of the virus appeared clearly differentiated from the nucleocapsid. The most important finding was that the cryosubstituted technique was able to preserve the structures of the flavivirus nucleocapsids which so far has not been convincing reported with chemical processing. PMID- 7868649 TI - The influence of antibody levels in dengue diagnosis by polymerase chain reaction. AB - The potential of RT-PCR to rapidly diagnose dengue infections from both acute and convalescent phase patients' sera was evaluated. The RNA extraction method involved binding of the viral RNA to silica particles in the presence of high concentration of guanidine thiocyanate. The protocol that was established was sensitive enough to detect 40 plaque forming units per 100 microliter of serum and results could be obtained within one day. Results from this study indicate that clinical samples should be collected in the early acute phase of illness when anti-dengue antibodies were undetectable or of low titres to ensure a more reliable diagnosis. PMID- 7868650 TI - Quantitative polymerase chain reaction for hepatitis B virus DNA. AB - To monitor and compare the effect of drugs on hepatitis B virus (HBV) replication in hepatitis patients, an accurate quantitative method with high sensitivity is needed. Polymerase chain reaction (PCR) is the most sensitive method for the detection of HBV DNA, but because of sample to sample variability in amplification efficiency, the quantification of target nucleic acids by conventional PCR is inaccurate. Therefore, we developed a competitive PCR method with an internal standard which uses the same primers as the target HBV DNA. The standard was generated from the HBV S gene by PCR site-directed mutagenesis and differed from the native S gene by a single base which introduced an internal restriction enzyme site. For practical application, this method was used to quantitate the effect of the carbocyclic analogue 2'-deoxyguanosine (2'-CDG) on HBV DNA replication in 2.2.15 cells, an HBV transfected HepG2 cell line. A decrease of HBV DNA level in the attomole range was demonstrated by the assay in the media of 2.2.15 cells treated with 2'-CDG. The results were verified by conventional HBV DNA slot blot analysis followed by densitometric scanning. Competitive PCR proved to be a sensitive, accurate and reliable method for HBV quantitation. PMID- 7868651 TI - A ligase chain reaction targeting two adjacent nucleotides allows the differentiation of cowpox virus from other Orthopoxvirus species. AB - A ligase chain reaction (LCR) assay was developed to distinguish cowpox virus from other Orthopoxvirus species. The LCR targets two adjacent adenosine residues which are only present in the A-type inclusion protein gene (ATI-gene) of cowpox virus. Two primer pairs were designed with a one base pair overlap at the junction site and one primer of each pair was labeled radioactively. Detection of the ligation product was achieved after denaturing polyacrylamide gel electrophoresis and autoradiography. Prior to LCR, the corresponding region of the ATI-gene was amplified by a consensus primer-directed polymerase chain reaction. All 18 cowpox virus isolates investigated could be clearly discriminated from 10 vaccinia virus strains, 5 camelpox virus isolates, as well as from mousepox and monkeypox virus reference strains. The LCR method allows a fast identification of cowpox virus isolates and is a feasible tool for the analysis of small mutations within viral genes. PMID- 7868652 TI - Use of competitive PCR to estimate the level of NS gene persisting in MDCK cells which survived productive replication of a mutant of influenza virus A/WSN. AB - Madin-Darby canine kidney (MDCK) cells, which received high multiplicity superinfections with a weakly cytolytic mutant of influenza A virus, could survive and be passaged stably, carrying the genes of the infected virus. The quantitation of the viral NS gene persisting in these cultured cells using competitive polymerase chain reaction revealed that the gene existed at a relatively constant level (approximately 10(5) to 10(6) copies per 8 x 10(6) cells) over a long range of cell generations without producing any detectable progeny virus, suggesting that the persisting NS gene was not silent, but was amplified and inherited to the daughter cells. PMID- 7868653 TI - Same-day testing for human immunodeficiency virus antibodies. AB - We analysed the specificity of a screening enzyme-linked immunosorbent assay for human immunodeficiency virus antibodies, and found that 18 of 1878 serum specimens (1.0%) from an open access clinic gave false reactive results. Introduction of true same-day testing therefore required the use of more than one assay before a reactive result could be reported. A testing strategy was devised with a 4 h turn-around time which gave accurate results for 11 positive and 119 negative specimens. PMID- 7868654 TI - Artificial insemination of single women and lesbian women with donor semen. Artificial insemination with donor semen: particular requests. PMID- 7868656 TI - Particular requests in donor insemination: comments on the medical duty of care and the welfare of the child. PMID- 7868655 TI - Donor insemination for single heterosexual and lesbian women: issues concerning the welfare of the child. PMID- 7868657 TI - Multifetal pregnancy reduction: the case for non-directive patient counselling. PMID- 7868658 TI - Multifetal pregnancy reduction: a useful tool, but a difficult choice. PMID- 7868659 TI - Increased rates of aneuploidy in older women. Increased rates of aneuploidy do not occur in gestations of older embryo recipients. PMID- 7868660 TI - Follicle cyst formation after administration of different gonadotrophin-releasing hormone analogues for assisted reproduction. AB - The aim of this study was to examine the occurrence of ovarian cysts during the administration of three different gonadotrophin-releasing hormone analogues (GnRHa) in the long protocol as well as their characteristics, management and outcome compared with patients with no cyst formation. A total of 172 in-vitro fertilization (IVF) cycles in which GnRHa was administered at menstruation were analysed. Group B consisted of 72 cycles in which buserelin was used. Of these, 10 (13.9%) were with cysts (group B1) and 62 (86.1%) without cysts (group B2). Group T included 49 cycles in which triptorelin was injected. Of these, seven (14.2%) were with cysts (group T1) and 42 (85.7%) without cysts (group T2). Group L comprised 51 cycles in which leuprolide was administered. Of these, eight (15.7%) were with cysts (group L1) and 43 (84.3%) without cysts (group L2). All women with ovarian cysts had higher serum oestradiol concentrations and all except five underwent cyst aspiration with no complication. No differences were observed in the number of follicles and oocytes between groups B, T and L or between the groups with cysts and those without cysts. The pregnancy rate was similar in all groups. In conclusion, follicle cyst formation does not seem to be related to the use of a specific GnRHa, its short- or long-acting form or to the mode of administration. In addition, follicle cyst aspiration is a safe and successful solution to the problem of functionally active ovarian cysts. PMID- 7868661 TI - Clinical significance of invisible or partially visible luteinizing hormone. AB - It is well known that luteinizing hormone (LH), like many other glycoproteins, is heterogeneous and presents several circulating isoforms. Recently, new sensitive immunometric assays measuring intact LH were developed. These assays have been found to underestimate or to be incapable of recognizing LH in some patients. This study was undertaken to determine the prevalence of such cases and to define their clinical characteristics. We compared three LH assays using as capture antibodies either a monoclonal antibody that reacts exclusively with intact LH (ES 600 Boehringer, Stratus Baxter) or a monoclonal antibody against the beta subunit of LH (IMX Abbott). In 17% of 90 patients tested, ES 600 measured > 50% lower LH concentrations when compared with the IMX. Moreover, in two cases LH was not detectable by ES 600 or Stratus, whereas it was normal with the IMX. We found another five such cases and discuss here the clinical data and results of different hormone measurements in these seven cases of 'invisible LH'. Although bioactive LH (mouse Leydig cell assay) was normal, the existence of low or even undetectable LH was clinically confusing and led to expensive complementary investigations such as gonadotrophin-releasing hormone analogue tests and magnetic resonance imaging. The uses and limitations of these assays are illustrated by different clinical situations in which the results of the different assays have been misleading. PMID- 7868662 TI - The effects of ICI 182,780, a pure anti-oestrogen, on the hypothalamic-pituitary gonadal axis and on endometrial proliferation in pre-menopausal women. AB - ICI 182,780 has shown pure oestrogen antagonism in vitro and in vivo in animals. A total of 17 women with normal menstrual cycles were administered ICI 182,780, 12 mg daily for 7 days in the follicular phase prior to hysterectomy; 11 normal women were used as controls. Of the 17 patients, three (18%) experienced a luteinizing hormone (LH) surge in the treatment group compared with five (45%) in the controls (P = 0.24), and these patients were only included up to the surge. There were no differences in the daily mean plasma LH and follicle stimulating hormone concentrations between the treatment (n = 17) and control (n = 10) groups. The mean plasma oestradiol was higher in the treatment group than controls (P < 0.05) on days 5, 6 and 7. However, there was no increase in endometrial thickness in the treatment group throughout the study. In the control group, endometrial thickness increased during the study and was significantly higher (P < 0.05) on day 7. There was no ultrasonic evidence of ovarian hyperstimulation and no serious adverse events reported. This study shows that treatment for 7 days with ICI 182,780 does not cause ovarian hyperstimulation and has a potent anti-oestrogenic action on the endometrium. We conclude that ICI 182,780 may be a useful compound in the treatment of oestrogen-dependent gynaecological disease. PMID- 7868663 TI - Ovarian stimulation in an infertile patient with growth hormone-deficient Oliver Mcfarlane syndrome. AB - Several authors have suggested that growth hormone may augment ovarian responses to follicle stimulating hormone in women (Homburg et al., Clin. Endocrinol., 29, 1988; Ibrahim et al., Fertil. Steril., 55, 1991), and that this effect may be mediated by insulin-like growth factor I (IGF-I) (Davoren and Hsueh, Endocrinology, 118, 1986). Menashe et al. (Hum. Reprod., 6, 1991) reported spontaneous pregnancies in women with a deficiency in growth hormone receptors and, consequently, low serum concentrations of IGF-I. In this report, we present the case of a patient with a rare syndrome first described by Oliver and Mcfarlane (Arch. Ophthalmol., 74, 1965). The patient was shown to be growth hormone deficient, with hypopituitarism as part of the syndrome. Adjuvant growth hormone did not influence her ovarian responses to exogenous gonadotrophins during assisted conception treatment, as reflected by the required total number of ampoules of human menopausal gonadotrophin, the number of developing follicles, the rate of follicular growth and the serum oestradiol concentrations. PMID- 7868664 TI - Effects of cholic acid and 'Protectaid' formulations on human sperm motility and ultrastructure. AB - Cholic acid (sodium cholate) and the other active ingredients of F-5 gel preparations in use for the impregnation of a new vaginal sponge (Protectaid) with contraceptive and anti-sexually transmitted disease properties, were assessed for their effects on human sperm motility and ultrastructure. Cholic acid (CA) produced an inhibition of motility which was both dose- and time dependent. A complete suppression of motility was obtained at 30 s by a CA concentration of 1.25%. Nonoxynol-9 (NX9) compared with benzalkonium chloride (BZC) showed no significant difference at the concentration required (0.025%) to give a total inhibition of sperm motility after exposure for 30 s. The addition of F-5A gel containing 0.5% of each one of the spermicide ingredients (CA, NX9 and BZC) produced the total suppression of sperm motility within 30 s at a dilution of 1/50. Another preparation, F-5B gel, containing the spermicide ingredients at different concentrations (1.25% CA, 0.125% NX9 and 0.05% BZC) produced this same effect with a 1/10 dilution. Exposure of semen to a CA concentration of 1.25% or to 1/10 dilutions of F-5A gel for 30 s led to profound changes of sperm ultrastructure studied by scanning (SEM) and transmission (TEM) electron microscopy. SEM and TEM findings indicate that CA acts as a spermicide through its 'natural detergent' properties, damaging the outer plasma membrane of sperm cells. Protectaid formulations affect sperm motility and viability in a similar way. PMID- 7868665 TI - Human leukocyte antigen typing and associated abnormalities in premature ovarian failure. AB - A case-controlled study was designed to assess the distribution of human leukocyte antigens (HLA) A, B, Cw, DR and DQ, and associated abnormalities in patients with premature ovarian failure (POF). A total of 37 patients in a tertiary care centre were diagnosed as having POF; all were < 37 years old. A subset was HLA-typed. The occurrence of associated diseases in patients with POF was recorded. A comparison of HLA typing was made between patients with POF and 100 organ donors from the same population. No statistically significant difference in the distribution of A, B, Cw, DR and DQ antigens was found between the study and control groups when corrected for the number of antigens tested. The commonest associated abnormality was positive autoimmune screen (43.3%). Abnormal thyroid function tests were detected in 23.3% of the patients. The observed high frequency of associated autoimmune phenomena in patients with POF points to an underlying autoimmune disorder in POF and warrants further studies to unravel the pathology of this condition. PMID- 7868666 TI - Predicting and optimizing success in an intra-uterine insemination programme. AB - We analysed 381 consecutive cycles of homologous intrauterine insemination (IUI) in 215 infertile couples, resulting in 48 pregnancies (12.6%/cycle, 22.3%/patient). Cycle fecundity ranged from 0.11 to 0.14 in women aged 25-39 years, falling to 0.04 beyond age 40 years. Of the 48 pregnancies, 43 occurred in the first three treatment cycles, in which fecundity was 0.14, 0.16 and 0.10 respectively. Beyond three cycles, fecundity was 0.07 (P = 0.05 versus first two cycles). The occurrence of pregnancy varied with diagnosis (P = 0.04). Fecundity was significantly greater for women with ovulatory dysfunction (0.30) than for endometriosis, male factor, tubal factor, idiopathic infertility or multifactorial (0.08-0.14). Ovulation induction using menopausal gonadotrophins offered significant advantage over natural cycles or cycles using clomiphene citrate without gonadotrophins (0.15 versus 0.03, P = 0.01). Cycles in which pre ovulatory surges were either induced or supported with human chorionic gonadotrophin (HCG) were superior to spontaneous luteinizing hormone surges (0.13 versus 0.03, P = 0.05). Recruitment of at least two mature (> 1.6 cm) follicles was critical. Only one pregnancy occurred in 64 cycles characterized by one mature follicle, compared with a pregnancy rate of 0.15 in cycles characterized by two or more mature follicles (P = 0.006). IUI is not beneficial to women > 40 years old, and has the best chance of success within three cycles. Multiple follicle recruitment using gonadotrophin-based stimulation protocols and mid cycle HCG are necessary to achieve an acceptable pregnancy rate. PMID- 7868667 TI - Intra-uterine insemination or timed intercourse after ovarian stimulation for male subfertility? A controlled study. AB - In this randomized trial we investigated whether intra-uterine insemination (IUI) in couples with male subfertility leads to a higher probability of conception than timed intercourse after ovarian stimulation with human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG). A total of 76 couples started 249 cycles, of which 47 were cancelled to prevent multiple pregnancies or hyperstimulation. After 202 completed treatment cycles, 15 pregnancies occurred, 11 after IUI and four after timed intercourse. The pregnancy rate per completed cycle with IUI was 10.3% (95% confidence interval: 5.5-17.5%) and 4.2% (1.2-10.1%) with timed intercourse. Compared with the estimated spontaneous chance to conceive, IUI after ovarian stimulation appeared to be more effective in the first three cycles. We conclude that in subfertile couples with a male factor, IUI tends to improve the probability of conception as compared to timed intercourse when ovarian stimulation is applied, and we advise such treatment for three cycles. PMID- 7868668 TI - Characterization of Tru-Trax in-vitro penetration testing of cervical mucus. AB - To determine the distribution of results of an in-vitro cervical mucus penetration system employing both human and bovine mucus (Tru-Trax) in a general infertility population, 133 couples prospectively underwent in-vitro and post coital testing of cervical mucus. The distribution of Tru-Trax results in couples with normal semen analyses and Insler scores showed significantly greater penetration in bovine (22.3 +/- 6.0 mm) than in human mucus (20.3 +/- 5.4 mm) (P < 0.001). However, the lower limit of the 95% confidence interval of the normal population with either type of mucus was approximately 10 mm. This limit was significantly lower than that described by the kit manufacturer. The predictive value for post-coital tests using human mucus in the Tru-Trax system was good (> 90%) in all groups. The overall penetration into either human or bovine mucus was significantly correlated with the percentage of motile spermatozoa in the semen sample (P < 0.001). In conclusion, in-vitro cervical mucus penetration tests with the Tru-Trax system are related to in-vivo post-coital tests, although the lower limit of the range of anticipated results in the normal population was significantly lower than that described by the manufacturer. The ultimate value of this type of testing will await clinical trials which evaluate clinical end points such as pregnancy rates. PMID- 7868669 TI - Five years' follow-up in two patients with borderline tumours of the ovary hyperstimulated by gonadotrophin therapy for in-vitro fertilization. AB - In two women (36 and 30 years old) during infertility evaluation by ultrasound, an ovarian cyst was found on the left side (5 x 7 and 6 x 9 cm respectively). In both cases, it was decided to perform a unilateral salpingo-oophorectomy, keeping the other ovary (after a negative biopsy) for a future in-vitro fertilization (IVF) procedure with their own oocytes. The histology report for each patient showed the cyst was an epithelial borderline tumour. The first woman achieved a pregnancy and delivered a healthy baby after the first IVF attempt, while the second is currently undergoing her third attempt. This paper reports on a follow up 5 years after the first IVF attempt. PMID- 7868670 TI - Familial blepharophimosis with ovarian dysfunction. AB - Three cases including two sisters and one brother with blepharophimosis are described. Their father also had blepharophimosis. Moreover, the elder sister initially presented with resistant ovary syndrome and thereafter true premature menopause, while the younger one presented with resistant ovary syndrome. The explanation for the association of blepharophimosis with primary ovarian dysfunction is unknown, but the possibility of a microdeletion of genetic material containing two geographically associated, but independent genes could not be confirmed or excluded. All families affected by blepharophimosis should be counselled about the high incidence of ovarian dysfunction and female infertility, at least in one form of the syndrome. PMID- 7868671 TI - Incubation of spermatozoa from asthenozoospermic semen samples with pentoxifylline and 2-deoxyadenosine: variability in hyperactivation and acrosome reaction rates. AB - We examined hyperactivation and acrosomal loss in asthenozoospermic patients with a history of failed in-vitro fertilization (IVF). After selection by a Percoll gradient, spermatozoa were incubated with 3.6 mM pentoxifylline (PTX), 3.0 mM 2 deoxyadenosine (2-DXA) or both. Hyperactivation and ionophore A-23187-induced acrosome reaction were assessed immediately after sperm treatment and again after 180 min. In all groups studied, the mean hyperactivation rates were found to be low. No significant differences were noted between assessments immediately after treatment and 180 min later, except after treatment with both PTX and 2-DXA. The mean hyperactivation rates were found not to improve as a result of either PTX or 2-DXA, while the combination of both PTX and 2-DXA revealed a significant enhancement of total hyperactivation. When individual hyperactivation rates between control and treated sperm samples were compared, large differences in response were observed. Some sperm samples showed a marked increase in hyperactivation with one treatment, while another treatment led to a decrease. Acrosome reaction rates assessed immediately after ionophore A-23187 stimulation were found not to be significantly different from those assessed 180 min later. No significant effect could be demonstrated for either treatment, although, here too, marked interindividual variations were noted. It was concluded that an unselective use of PTX, 2-DXA or both compounds together, may restore sperm function in certain of these patients, and perhaps improve fertilization in vitro, but in others it may produce no change or may even be detrimental to sperm function. PMID- 7868672 TI - Glutathione treatment of dyspermia: effect on the lipoperoxidation process. AB - We recently introduced reduced glutathione into the therapeutic protocols in some selected cases of dyspermia. This therapy improved semen quality both in a pilot follow-up study and in a double-blind cross-over trial. This improvement was seen in patients with varicocele and germ-free genital tract inflammation, two pathologies in which production of reactive oxygen species or other toxic compounds could have a pathogenic role. Polyunsaturated fatty acids of phospholipids play a major role in membrane constitution and function and are one of the main targets of the lipoperoxidative process. Therefore, to understand the therapeutic action of reduced glutathione, we selected infertile patients and studied the modifications produced by the therapy in seminal parameters, biochemical sperm membrane parameters, and the pattern of fatty acids of phospholipids from blood serum and red blood cell membranes (a model widely accepted as representative of general cell membrane status). The results showed an improvement in both sperm parameters and cell membrane characteristics. This study suggests that biochemical modifications in membrane constitution could explain the seminal results of glutathione therapy. On the other hand, it seems likely that only subjects with systemic membrane disturbances associated with andrological pathologies express this membrane damage in spermatozoa, resulting in dyspermia. This sperm alteration can be partially reversed by glutathione therapy if the structural cell membrane damage is not too severe. PMID- 7868673 TI - Successful treatment of severe male factor infertility in 100 consecutive cycles using intracytoplasmic sperm injection. AB - In this report, we present the results of our first 100 consecutive cycles of intracytoplasmic sperm injection (ICSI). Overall, fertilization occurred in 98% of cycles and embryos were transferred in 94% (2.6 embryos per cycle). About 50% of patients had embryos frozen. The overall fertilization rate was 71%, of which 4% were abnormally fertilized (three pronuclei). A total of 30 clinical pregnancies were established (32% per transfer), resulting in 18 singleton, six twin and one triplet ongoing pregnancies. The implantation rate per embryo was 15%. There were no significant differences in the fertilization or pregnancy rates between patients who had only occasional motile spermatozoa in the ejaculate, semen that was too poor for routine in-vitro fertilization (IVF), or who had failed routine IVF and/or subzonal sperm injection (SUZI). A group of 18 patients were treated with both ICSI and routine IVF on their first cycle because of the high likelihood of failed fertilization due to poor sperm morphology < 20% normal). In this group, ICSI oocytes had a fertilization rate of 76% compared to only 15% for the routine IVF (control) oocytes, and six patients conceived after transfer of ICSI embryos (33%), indicating that ICSI can be used successfully on 50% of the oocytes if fertilization failure is expected. Similarly, patients who had failed to become pregnant with SUZI achieved excellent results after ICSI. There were no significant differences between ICSI and routine IVF in the proportions of grade 1, 2 or 3 embryos on day 3 post-oocyte recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868674 TI - Percutaneous epididymal sperm aspiration for obstructive azoospermia. AB - We report the use of percutaneous epididymal sperm aspiration as a simpler and more acceptable alternative to microscopic epididymal sperm aspiration for patients with obstructive azoospermia in whom bypass surgery is not feasible or has not been successful. Some contamination of the aspirate with blood is inevitable, but with careful sperm preparation techniques this can be reduced substantially in the final aliquot used for assisted conception. Spermatozoa with active forward progression may be used for gamete intra-Fallopian transfer treatment, but when this capacity is absent intracytoplasmic sperm injection is recommended. Three pregnancies were obtained in seven couples and a set of twins has been delivered. PMID- 7868675 TI - Germ cell and Sertoli cell interactions in human testis: evidence for stimulatory and inhibitory effects. AB - In human Sertoli cell preparations obtained from healthy men (mean age 31.8 +/- 6.8 years; n = 6), we have measured the productions of lactate, 17 beta oestradiol, transferrin and inhibin between day 4 and day 5 after plating, either in the presence or absence (hypotonic treatment of plated cells on day 2) of germ cells. The results, expressed per 10(6) of cells plated/24 h, showed that lactate production was unchanged, whether or not germ cells were present. However, if we calculated the lactate production per mg protein/24 h, the lactate output was decreased (30-60%) in the presence of germ cells. Whatever the mode of expression, Sertoli cell 17 beta-oestradiol synthesis was diminished 1.5-fold in the presence of germ cells. Conversely, the transferrin output was increased 3.2 fold in non-treated Sertoli cell preparations when compared to the hypotonic treated plates. A similar observation was recorded for the in-vitro production of inhibin by Sertoli cells, which was enhanced 1.4-fold when germ cells were present. These results, together with a likely potentializing role of germ cells on follicle stimulating hormone control of Sertoli cell function, strongly suggest that germ cells exert both stimulatory and inhibitory effects in regulating human Sertoli cell function through either direct contact and/or via secreted factors. PMID- 7868676 TI - Improved diagnosis of male fertility potential via a combination of quantitative ultramorphology and routine semen analyses. AB - The aim of this study was to develop a new male fertility diagnostic profile based on quantitative ultramorphology parameters and to determine the contribution of this profile to the enhancement of the routine semen analysis index reported previously. Semen samples from 208 males of known fertility and suspected infertility were evaluated for the ultrafine structure of the following sperm cell organelles: acrosome, post-acrosomal lamina, nucleus, neck, axonema, mitochondrial and fibrous sheaths. For each of these organelles, four pathological states (agenesis, incomplete genesis, malformation and degradation) and an intact state were defined. A quantitative ultramorphology index based on the incidence of intact nucleus, acrosome and fibrous sheath malformations enabled high accuracy in the classification (97% sensitivity and 90% specificity) of 74% of the cases. A combined semen quality index based on a proportional combination of the semen analysis and quantitative ultramorphology indices was found to increase the percentage of cases classified correctly to 80%. It was proposed that semen specimens of males whose fertility status cannot be predicted clearly using routine semen analysis should be fixed and sent for quantitative ultramorphology analysis to specialized laboratories so that their fertility potential can be determined more accurately using the semen quality index. PMID- 7868677 TI - The screening for cytomegalovirus antibody in semen donors and recipients within a donor insemination programme. AB - A total of 67 semen donors (62 Caucasian and five non-Caucasian) were tested for the presence of immunoglobulin G antibodies to cytomegalovirus (CMV). Ten (16%) of the Caucasian donors tested positive for CMV, while four (80%) of the non Caucasian donors were positive. A total of 131 women receiving donor insemination (114 Caucasian and 17 non-Caucasian) were tested. Of these, 43 (38%) of the Caucasian recipients tested positive for CMV, while 16 (94%) of the non-Caucasian recipients were positive. There was a significant association between the incidence of positive tests and the age of the Caucasian recipients. PMID- 7868678 TI - The acrosome reaction to ionophore challenge test: assay reproducibility, effect of sexual abstinence and results for fertile men. AB - Since the human acrosome reaction is considered a prerequisite for normal fertilization and the spontaneous acrosome reaction rate is low, laboratory tests using calcium ionophores to induce the acrosome reaction have been devised and applied to the investigation of patients. The introduction of any new laboratory test into routine clinical practice is usually accompanied by the determination of intra- and inter-subject variability within the normal population, and the derivation of reference values to distinguish between affected and unaffected populations. The acrosome reaction to ionophore challenge (ARIC) test was evaluated and found to have (i) intra- and inter-assay coefficients of variation of 10.8 and 18.8% respectively, (ii) a high degree of intra-subject variability for three subjects studied over a 10 week period, (iii) a high degree of inter subject variability when aliquots of 20 ejaculates of donor semen of proven fertility were tested, and (iv) no effect of length of sexual abstinence on ARIC values. The results of this study suggest that the use of fresh semen samples from subjects of proven fertility for quality control purposes in the ARIC test may be inadequate due to the high degree of intra-subject variability, and that this problem may be overcome by utilizing a frozen quality control sample. The results also suggest that an isolated negative ARIC test is not necessarily indicative of functionally incompetent spermatozoa, and highlight the importance of examination of the normal population prior to the clinical application of such a test. PMID- 7868679 TI - Total laparoscopic hysterectomy: preliminary results. AB - Total hysterectomy carried out entirely via laparoscopy benefited 31 patients. In all cases the operation was carried out using conventional, re-usable instruments (grasping forceps, laparoscopic scissors, bipolar coagulation). The mean duration of the operation was 171 min. No serious peri- or post-operative complications were encountered and no transfusion was required. The mean drop in haemoglobin was 1.3 g/100 ml and the average length of hospital stay was 4 days. In one case (3.26%) we converted to laparotomy because a lateral myoma made it impossible to achieve haemostasis of the uterine pedicle under suitably safe conditions. These results confirm that total hysterectomy via laparoscopy is a safe, feasible and reproducible technique. Future work will establish the exact place and methods for laparoscopic surgery for hysterectomy; it can be suggested, however, that laparoscopic surgery is only indicated when vaginal hysterectomy is contra indicated or impossible. So, laparoscopic hysterectomy constitutes an alternative to laparotomy rather than to vaginal hysterectomy. The combination of an immobile uterus and poor vaginal accessibility is the prime indication for total hysterectomy via laparoscopy. PMID- 7868680 TI - Hydrosalpinx formation and its regeneration after microsurgical reconstruction--a functional and morphological study on rabbits. AB - The development of mechanically induced hydrosalpinx and the subsequent regeneration of the uterine tube following correction were investigated with reference to morphological and functional parameters in 33 rabbits. Mechanically induced hydrosalpinx leads to reduced fertility. The characteristic morphological alterations are flattening of the folds, deciliation, reduced secretory activity and general de-differentiation of the epithelial cells. The intensity of these changes peaked as little as 4 weeks after induction of the hydrosalpinx. The deciliation is generally patchy. The division into different fields, islet formation and celestial chart phenomena reflect different degrees of vascularization and/or oxygenation. These alterations were completely reversible within 8 weeks after reconstruction. In isolated cases only the formation of polypose stumps was seen, which were, however, covered with a normal epithelial surface. The discrepancy between the reduced tubal function following reconstruction for hydrosalpinx and the complete regeneration of the tubal mucosa suggests that other regulatory mechanisms more important for the function of the uterine tube are impaired. PMID- 7868681 TI - Effect of pentoxifylline and progesterone on human sperm capacitation and acrosomal exocytosis. AB - The effects of pentoxifylline and progesterone on human sperm capacitation and acrosomal exocytosis were investigated using chlortetracycline (CTC) fluorescence. Continuous exposure to 3.60 mM pentoxifylline caused significant changes in distribution of the three CTC patterns (F, B and AR) compared with control suspensions. Initially, the main effect was promotion of the F to B transition, followed by increases in acrosome-reacted (AR) pattern cells as well. Such responses would be consistent with a pentoxifylline-mediated inhibition of cAMP phosphodiesterase leading to increased availability of cAMP. When continuous and short-term exposure to pentoxifylline were compared, very similar responses were observed: both pentoxifylline-treated groups had significantly more capacitated cells (B and AR patterns) than controls. Progesterone tested at 1, 10 and 100 micrograms ml-1 elicited a similar response to that observed with pentoxifylline, with both capacitation and acrosomal exocytosis being stimulated. Cells incubated in 2 x Ca2+ (3.6 mM) medium were even more responsive to progesterone treatment than those in standard 1 x Ca2+ (1.8 mM) medium, with a threefold decrease in cells exhibiting the F pattern (characteristic of uncapacitated, acrosome-intact cells) and a marked increase in AR cells. These responses are consistent with a progesterone-mediated rise in intracellular Ca2+ that could promote completion of capacitation and initiation of acrosomal exocytosis. Used in combination, pentoxifylline followed by progesterone treatment produced significantly more AR pattern cells than either compound individually.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868682 TI - Isolation and culture of inner cell mass cells from human blastocysts. AB - Totipotent non-committed inner cell mass (ICM) cells from human blastocyts, if demonstrated to be capable of proliferating in vitro without differentiation, will have several beneficial uses, not only in the treatment of neurodegenerative and genetic disorders, but also as a model in studying the events involved in embryogenesis and genomic manipulation. Nine patients admitted to an in-vitro fertilization programme donated 21 spare embryos for this study. All 21 embryos were grown from the 2-pronuclear until blastocyst stages on a human tubal epithelial monolayer in commercial Earle's medium (Medicult, Denmark) supplemented with 10% human serum. The medium was changed after blastocyst formation to Chang's medium supplemented with 1000 units/ml of human leukaemia inhibitory factor (HLIF) and the embryos left undisturbed for 72 h to allow the hatched ICM and trophoblast to attach to the feeder monolayer. Nineteen of the 21 embryos from nine patients produced healthy ICM lumps which could be separated and grown in vitro. Two of the lumps differentiated into fibroblasts while the remaining 17 (eight patients) produced cells with typical stem cell-like morphology, were alkaline phosphatase positive and could be maintained for two passages. It was possible to retain the stem cell-like morphology, alkaline phosphatase positiveness and normal karyotype through the two passages in all of them using repeated doses of HLIF every 48 to 72 h. This is the first report on the successful isolation of human ICM cells and their continued culture for at least two passages in vitro. PMID- 7868683 TI - Autocrine/paracrine function of transforming growth factor-beta 1 in porcine granulosa cells. AB - The present study was undertaken to investigate the effects of transforming growth factor (TGF)-beta 1 on ovarian steroidogenesis in immature or moderately mature porcine granulosa cells in vitro. TGF-beta 1 (0.01-10 ng/ml) significantly attenuated progesterone release from the basal and follicle stimulating hormone stimulated porcine granulosa cells, and significantly increased DNA synthesis. TGF-beta 1 also significantly increased the extracellular accumulation of cyclic AMP, but did not change the production of inositol phosphate or the intracellular calcium concentration in these cells. Thus, TGF-beta 1 appears to have a direct effect on porcine granulosa cell function, regulating the differential synthesis of progesterone mainly via the intracellular signal transduction of the cyclic AMP-protein kinase A pathway. This growth factor may play a physiologically significant role in controlling differentiation of immature and moderately mature porcine granulosa cells via an autocrine/paracrine mechanism. PMID- 7868684 TI - Timing of development is a critical parameter for predicting successful embryogenesis. AB - Development of embryos from the 1-cell stage into blastocysts in vitro is generally slower than the time-course for development in vivo. It was the objective of this work to determine whether embryos that reach the 8-cell stage within a normal time-frame have a developmental advantage (both in vitro and post embryo transfer) over slower embryos. Hamster 1-cell embryos were collected 10 h post-egg activation (PEA) and cultured for 48 h (58 h PEA = t50 for 8-cell embryo development in vivo) in hamster embryo culture medium-6. Embryos were sorted according to stage reached, culture was continued in fresh medium and stage of development was observed at 78, 82 and 86 h PEA. At 58 h PEA, embryos were < 4 cell (4%), 4-cell (19%), 5- to 7-cell (16%) or 8-cell (61%). The 58 h 8-cell embryos had a significantly greater ability to develop to the blastocyst stage than 58 h 4-cell embryos at 78, 82 and 86 h PEA (74 versus 13%, 69 versus 25% and 65 versus 37% respectively). The percentages of 14-day-old fetuses collected after embryo transfer indicated that morulae and blastocysts derived from 58 h 4 cell embryos were, on average, less viable (26% fetuses) than morulae and blastocysts from 58 h 8-cell embryos (51% fetuses). Thus morulae and blastocysts developing in vitro from faster or slower cleaving embryos can be qualitatively as well as quantitatively different. These data indicate that the timing of development in vitro, specifically the timing of completion of the third cell cycle, is a critically important parameter for predicting successful embryogenesis in the hamster. PMID- 7868685 TI - Antral follicle development and in-vitro maturation of oocytes from macaques stimulated with a single subcutaneous injection of pregnant mare's serum gonadotrophin. AB - A single s.c. injection of 1000 IU of pregnant mare's serum gonadotrophin (PMSG) stimulates the growth of multiple antral follicles in cynomolgus monkeys (Macaca fascicularis). The number of cumulus-enclosed oocytes (CEO) from six non stimulated controls was 36 (mean = 6). In contrast, a total of 95 CEO (mean = 31.7) were recovered from three animals stimulated and ovariectomized 3 days later, while 385 CEO (mean = 128.3) were obtained from three animals stimulated and ovariectomized 4 days later. A comparison of the effects of highly purified human follicle-stimulating hormone (FSH), human luteinizing hormone (LH) and human thyroid-stimulating hormone (TSH) on cultures of rhesus monkey (Macaca mulatta) CEO cultured in medium 199 for 48 h showed that FSH and LH stimulated cumulus expansion but had moderate effects on the progression of meiosis. The progression that did occur seldom proceeded beyond the metaphase I stage. Human TSH had no demonstrable effect on cumulus expansion and meiotic progression. In other experiments FSH, LH and oestradiol-17 beta were added jointly to medium CMRL 1066 in which CEO from non-PMSG-stimulated and PMSG-stimulated cynomolgus monkeys were cultured for 48 h. If the CEO were obtained from non-PMSG-stimulated monkeys the hormones caused a significant cumulus expansion, but had only a limited effect on meiotic progression. However, if the CEO were obtained from PMSG-stimulated monkeys there was a significant stimulation of cumulus expansion and meiotic progression. The hormone treatment resulted in a yield of 72.8% metaphase II oocytes compared with 40.9% in the controls. PMID- 7868686 TI - The zona reaction in human oocytes as seen with scanning electron microscopy. AB - Using scanning electron microscopy we found differences in the fine structure of the zona pellucida between unfertilized and fertilized human pronuclear stage oocytes in an in-vitro fertilization programme. In unfertilized oocytes, the zona pellucida appeared porous, comprising a large number of ring-shaped structures, called hoops, randomly superimposed in several layers. Superficial pores had a mean diameter of 4 microns, with the diameter decreasing in more inner lying pores. In fertilized oocytes, the zona pellucida was compact; the hoops appeared to melt and the pores to be obliterated by an amorphous material emerging from the inner zona. The micrographs provide ultrastructural evidence of the zona reaction in human oocytes and give insights into the morphological and mechanical aspects of the polyspermy-blocking mechanism in humans. PMID- 7868687 TI - Behaviour of spermatozoa in human oocytes displaying no or one pronucleus after intracytoplasmic sperm injection. AB - The behaviour of sperm cells after intracytoplasmic sperm injection (ICSI) was investigated by analysing 192 unfertilized and 37 one-pronuclear (1PN) oocytes following ICSI. Eighty-two unfertilized oocytes were directly fixed whereas 110 were first parthenogenetically activated by puromycin. In contrast to the findings in unfertilized oocytes after in-vitro fertilization, most unfertilized oocytes after ICSI (n = 76) contained evidence of the presence of spermatozoa in the cytoplasm. Few oocytes (n = 6) contained prematurely condensed sperm chromosomes (PCC), whereas the majority contained either intact sperm heads (n = 31) or swollen sperm nuclei (n = 39) along with metaphase II chromosomes of the oocyte. Following activation by puromycin, swollen sperm nuclei and PCC were no longer observed, whereas unchanged sperm heads persisted in 12 oocytes displaying a single pronucleus. A non-decondensed sperm nucleus along with decondensed maternal chromatin were also discovered in 32 out of 37 oocytes displaying a single pronucleus after ICSI. The findings in unfertilized and 1PN oocytes after ICSI indicate that successful sperm injection, even followed by oocyte activation, is not sufficient to guarantee normal fertilization. It seems that partial sperm membrane damage prior to injection is also required to ensure normal sperm decondensation. PMID- 7868688 TI - Sexing sibling mouse blastomeres by polymerase chain reaction and fluorescent in situ hybridization. AB - The diagnosis of human genetic diseases at preimplantation stages allows the transmission of genetic anomalies in high risk couples to be prevented. Embryo sexing can be carried out using the polymerase chain reaction (PCR) or by fluorescent in-situ hybridization (FISH). However, it is still questionable whether the results obtained from a single analysed cell are fully predictive of the genetic characteristics of the whole embryo. We have isolated all the blastomeres from 4-cell stage mouse embryos and analysed them by PCR and FISH to assess the consistency of the results obtained. One half of each embryo (2/4 embryo) was spread and fixed to be processed by FISH, while the blastomeres of the other half embryo were isolated (1/4 + 1/4-embryo) and individually processed for PCR. We have determined the efficiency of both techniques when applied to different cells of the same embryo. We were able to amplify 92.5% of the embryos. Of these, 91.8% were classified as male or female, while the remaining 8.2% gave contradictory results (one male and its sibling blastomere female). Of the 40 embryos analysed by FISH, 97.5% could be classified as male or female with a sex distribution close to the expected 1:1. When comparing both techniques, 24 out of 36 embryos gave the same result. In nine cases the results did not coincide, and in three embryos comparison was not possible because of PCR contradictory results. PMID- 7868689 TI - Recycling the single cell to detect specific chromosomes and to investigate specific gene sequences. AB - We have developed a new procedure, called cell recycling, which combines the two powerful techniques of polymerase chain reaction (PCR) and fluorescent in-situ hybridization (FISH) on the same single cell. A fixed cell is used as the DNA template for PCR, prior to the FISH analysis. Using single blastomeres from mouse embryos as a model system, cell recycling procedures detect the single-copy beta haemoglobin gene sequence at an efficiency of 70% as well as sex chromosome constitution at an efficiency of 74% in the same single cell. Cell recycling will increase the success rate of pregnancy following preimplantation diagnosis for a specific gene defect by identifying embryos with chromosomal abnormalities and eliminating them from the transfer procedure. PMID- 7868690 TI - Twin pregnancy after preimplantation diagnosis for sex selection. AB - A twin female pregnancy was obtained in a haemophilia carrier after two preimplantation diagnosis cycles. The embryonic sex of biopsied blastomeres was determined with the use of dual fluorescence in-situ hybridization with directly labelled DNA probes specific for the X and Y chromosome. A twin female pregnancy was confirmed by means of ultrasonography and amniocentesis at the 14th week of amenorrhoea. The patient delivered two healthy females by Caesarian section at the 37th week of pregnancy. PMID- 7868691 TI - Oocyte donation in humans: a model to study the effect of age on embryo implantation rate. AB - Although a number of different mechanisms have been suggested to account for the decline of fertility with age, the majority of studies agree that poor oocyte quality and reduced endometrial receptivity are the most important. In fact, the increased incidence of early pregnancy loss and chromosomal abnormalities of oocytes in older women, as well as the ability to reverse decreasing pregnancy rates by using oocyte donation, strongly support the evidence that oocyte ageing is the main factor responsible for decreasing fertility. Conversely, the lack of knowledge of the physiological variables that determine a successful nidation of a human embryo makes the analysis of uterine receptivity much more difficult. In order to evaluate the impact of the age of donors and recipients on pregnancy, implantation and abortion rates, we have retrospectively analysed 258 cycles from our programme of oocyte donation. Results were reviewed according to the following subclasses of age groups: < or = 30, 31-35 and 36-39 years for donors, and < or = 30, 31-35, 36-40, 41-45 and 46-53 years for recipients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868692 TI - Apparent lack of seasonal variation in implantation rates after in-vitro fertilization. AB - It has been suggested that seasonal variation in endometrial receptivity may occur in women, which could affect the likely success of in-vitro fertilization (IVF) treatment. We therefore studied implantation rates (fetal sacs as a proportion of embryos transferred) as an indirect index of receptivity in a narrowly defined population of women under 40 years old with normal ovulatory cycles and normal uterus and men with normal sperm function. A total of 577 cycles of IVF treatment were undertaken using a standard protocol of pituitary desensitization and ovarian stimulation during the 3 years 1990-1992. Results were compared between calendar months and 3-month seasons. The overall implantation rate was 14.9% of embryos, and the clinical pregnancy rate was 30.3% of cycles reaching egg collection. There were no significant differences in the monthly rates of eggs collected, fertilization and cleavage, or embryos transferred. Implantation rates varied to a greater extent but analysis of variance showed no seasonal variation. These findings do not support a seasonal variation in ovarian responsiveness or endometrial receptivity when stimulated for IVF treatment, but larger studies are needed for firm conclusions to be drawn. PMID- 7868693 TI - A comparison of medical abortion (using mifepristone and gemeprost) with surgical vacuum aspiration: efficacy and early medical sequelae. AB - A total of 363 women undergoing legal abortion at < 63 days of amenorrhoea were allocated by a patient-centered, partially randomized study design to undergo medical abortion (using mifepristone 600 mg followed 48 h later by gemeprost 1 mg vaginal pessary) or vacuum aspiration (performed under general anaesthesia). The aim of the study was to compare the efficacy and complications of the two procedures. Main outcome measures included efficacy rates, medical complications within 21 days of abortion and unplanned family doctor consultation rates within 8 weeks following abortion. Sequelae such as pain, vaginal bleeding and recovery time were assessed by the change in haemoglobin level, the time taken to return to work or normal activity and the analgesic use. Results were gestation-related; at 50 days of amenorrhoea there was little to choose between the two procedures. At 50-63 days of amenorrhoea medical abortion becomes more painful and less effective, whereas vacuum aspiration retains high tolerance and efficacy. Women who are unsure which method to use are likely to find vacuum aspiration more acceptable at longer gestations. PMID- 7868694 TI - Cervical ripening with the cytokines interleukin 8, interleukin 1 beta and tumour necrosis factor alpha in guinea-pigs. AB - It has been suggested that the collagenolytic enzymes released from white blood cells which infiltrate the pregnant human uterine cervix at term are responsible for connective tissue changes which take place during the ripening process. Similarly, an infiltration of inflammatory cells occurs in pregnant guinea-pigs either spontaneously at term or at preterm after treatment with the antiprogestin onapristone. The objective of this study was to evaluate the effects of the inflammatory cytokines interleukin 8 (IL-8), interleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and a combination of IL-1 beta and TNF alpha on cervical ripening in guinea-pigs during advanced pregnancy. The cytokines were applied locally (intracervically) in a gel for 2 days and the effects were assessed on the third day by both extensibility measurements and morphological evaluation. IL-8 treatment on days 42 and 43 post coitum (p.c) and on days 48 and 49 p.c. (term: day 67 +/- 3 p.c.) significantly (P < 0.05) increased cervical extensibility at both stages of pregnancy. Although IL-1 beta treatment (days 42 and 43 p.c.) led to a slight increase in cervical extensibility, this effect was not statistically significant. An electron microscope study performed on days 48 and 49 p.c. revealed a pronounced cervical ripening accompanied by the dissolution of collagen fibres, stromal oedema and the infiltration of polymorphonuclear leukocytes in all cytokine-treated groups. The morphological effects of IL-8 and IL-1 beta were indistinguishable from those observed during normal cervical ripening at term.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868696 TI - Intravenous albumin and severe ovarian hyperstimulation. PMID- 7868695 TI - A child at all costs: posthumous reproduction and the meaning of parenthood. AB - The creation of babies by assisted and collaborative techniques of reproduction, such as in-vitro fertilization or cryopreservation of gametes and embryos, stimulates strong emotions and fantasies about life, death, sexuality and immortality. Particularly, the cryopreservation of spermatozoa for post-mortem reproduction forces us to come to terms with the meaning of human reproduction, and the extent of individual rights to procreate using artificial means. PMID- 7868697 TI - The status and the state of the human epididymis. AB - As far as can be determined now, the general organization of the human epididymis, the regional character of its epithelium and luminal environment, and the maturation changes that spermatozoa undergo there are quite similar in many respects in both animals and man. None the less, the outcomes of some clinical procedures aimed at overcoming duct obstruction (high epididymovasostomy or microaspiration of some fertile spermatozoa from the caput or vasa efferentia) suggest a flexibility in the sperm/epididymal relationship that may cast an element of doubt as to the essential place of the epididymis in the chain of human conception. While such clinical results make it difficult yet to be quite sure that the epididymis has the same essential sperm maturation role in man that it does in the few animals tested, they raise intriguing questions as to the potential ability of the human vas deferens, and even the vasa efferentia, to contribute in that respect. The human epididymis possesses other traits which collectively seem to resemble the suppressive effects of subjecting animal epididymides to body temperature. In that regard, it is a real possibility that the elevation of scrotal temperature imposed by clothing may be affecting in an adverse manner several aspects of epididymal function, especially those concerned with the storage and viability of spermatozoa, and thereby the quality of the ejaculate. PMID- 7868698 TI - Attention deficit disorder in children: three clinical variants. AB - A clinic-referred population of 116 children with attentional problems was classified by DSM-III [attention deficit disorder (ADD)] with respect to inattention, impulsivity, and hyperactivity. The sample proved to subdivide into three groups: inattentive, impulsive, and hyperactive (HII), n = 60; inattentive and impulsive (II), n = 26; and inattentive (I), n = 30. The distinction between II and I resolves the confounding of impulsivity and inattention in previous studies of children who have ADD but are not hyperactive. The three groups were found to be similar in mean age, gender ratio, prevalence, and pattern of associated learning disabilities, family history of psychopathology, and probability of favorable response to methylphenidate. Group I differed from Groups HII and II in the frequency of externalizing relative to internalizing comorbid psychopathology. A group that is hyperactive and impulsive but not inattentive was not found. The preponderance of similarities in associated characteristics suggests that the three groups are differing clinical presentations of an ADD spectrum. PMID- 7868699 TI - Marital quality of parents of children with spina bifida: a case-comparison study. AB - The impact of childhood chronic illness on parents' marital quality has received limited attention. Most studies have relied solely on mothers' reports and have not examined differences between mothers and fathers. Using a case-control design, this study compared the marital quality within and between dyads of 46 couples with children matched on the age and children matched on the age and sex of the child. During a home visit, parents completed both self-report measures and a communication observational task. Mothers' and fathers' reports of marital quality did not differ between the two groups. Also, no significant differences were found on other marital and psychosocial measures. The most interesting correlations were observed for fathers of children with spinal bifida whose marital quality was associated with parenting stress (r = -.51), depression (r = .34), and role strain (r = -.34). Overall, the results of this study contribute to the growing body of literature demonstrating that parents of children with a chronic condition are at no greater risk for psychosocial dysfunction, including marital distress, than parents of healthy children. However, to generalize the results, additional research on marital quality with other chronic conditions is required. PMID- 7868700 TI - Contribution of coping to medical adjustment and treatment responsibility among children and adolescents with diabetes. AB - Youngsters with diabetes face numerous, daily challenges associated with their treatment. Previous research has examined coping in relation to global medical adjustment. However, the role that coping with diabetes-specific stressors plays in adherence to different treatment components, and child responsibility for these components, is not well understood. The present study examined the contribution of coping strategies to medical adjustment (i.e., metabolic control, treatment adherence) and level of child responsibility for treatment among children (n = 27) and adolescents (n = 29) with diabetes. Youngsters reported coping strategies in response to three diabetes-related situations (social, diet, fingerprick). Coping strategies accounted for a significant proportion of the variance in predicting most adjustment and responsibility variables, above and beyond the effects of relevant background variables (i.e., age, duration of diabetes, diabetes knowledge). Higher levels of approach-coping strategies related to better adherence to diet. Higher levels of avoidance-coping strategies related to poorer metabolic control and adherence to fingerpricks and higher levels of child responsibility for diet. These findings suggest that the role that coping strategies play in youngsters' medical adjustment is best understood within the context of diabetes-specific situations. PMID- 7868701 TI - Family psychosocial screening: should we focus on high-risk settings? AB - The objective of this study was to address the question of whether or not psychosocial screening should be focused on "high-risk" populations. A cross sectional survey of mothers of young children was conducted in various clinics: 758 in teaching clinics, 444 in private practices, and 202 at a military clinic. The self-administered questionnaire covered demographic factors, problems in mothers family of origin, maternal depression, and substance abuse. Mothers in the teaching clinics were younger and had less education and lower incomes than mothers in private practices, with intermediate levels in the military clinic. However, a substantial proportion of mothers seen in all sites reported psychosocial problems. Approximately 20% of mothers in all sites reported a family history of alcoholism. Positive screens for maternal depression ranged from about 15% to 35%. Binge drinking was reported by 10% to 20% at different sites. Psychosocial problems were common even among families seen in "low-risk" settings. Focusing screening only on high-risk clinics would miss many families with psychosocial problems. PMID- 7868702 TI - Neonatal temperament in full-term twin pairs discordant for birth weight. AB - To examine the significance of relative birth weight of cotwins for neonatal temperament, 70 pairs of full-term twins who were at least 15% discordant for birth weight were assessed. The assessment focused on irritability, resistance to soothing, activity, reactivity, and reinforcement value. The larger twin of the pair was more irritable, more difficult to soothe, more active while awake, more active during sleep, less reactive to visual and auditory stimuli, and less reinforcing to the examiner than the smaller cotwin. Both the lighter and heavier cotwins exhibited behavioral discrepancies. The results are discussed in relation to prenatal influences on early behavioral development, and implications for differential parent-infant interaction with each twin. PMID- 7868703 TI - Do parental concerns predict a diagnosis of attention-deficit hyperactivity disorder? AB - Parents' concerns for their children's behavior were investigated to predict a diagnosis of attention-deficit hyperactivity disorder (ADHD) in this retrospective comparative study of 245 children, aged 4 through 15 years (mean = 8.1 years), consecutively referred for comprehensive pediatric evaluation of school problems between 1981 and 1992. Concerns identified by parents were categorized (inattention, impulsivity, overactivity) and compared to children's final diagnoses of ADHD to measure their sensitivity, specificity, and predictive value. For 92% of subjects, significant school-related problems were diagnosed and 38% received a diagnosis of ADHD. Parental concern for one or more major symptoms of ADHD identified almost all of the children with a diagnosis of ADHD (sensitivity = .87), but also identified many children without such a diagnosis (specificity = .41). Concerns with impulsivity and overactivity were specific (.82, .87) but not sensitive (.38, .29). Concerns with attention had modest sensitivity (.57) and specificity (.57). Positive predictive value was modest for all categories of concerns (.45 to .57). Findings support the importance of eliciting parents' concerns for their children's school performance and of performing comprehensive assessment to identify the underlying causes of problems with attention. PMID- 7868704 TI - Sibling adaptation to childhood cancer collaborative study: prevalence of sibling distress and definition of adaptation levels. AB - A multisite collaborative study assessed the frequency and intensity of emotional/behavioral distress in siblings of children with cancer. A sample of 254 siblings, aged 4 to 18 years, and their parents completed interviews and self report measures 6 to 42 (average 22.5) months after diagnosis of cancer in a brother or sister. Matched controls were obtained from respondents to the Child Health Supplement of the National Health Interview Survey administered in 1988 (CHS88). Before diagnosis, the prevalence of parent-reported emotional/behavioral problems among siblings was similar to that in the general population (7.7% vs 6.3%; p = not significant). After diagnosis, prevalence rose to 18% among siblings. When siblings were grouped according to the presence or absence of problems exacerbated by and/or arising after diagnosis, four levels of adaptation, consistent with scores on the Behavior Problem Scales from the CHS88, emerged. This differentiation may help explain inconsistencies in sibling response reported previously and provides a framework for investigating factors that enhance adaptation. PMID- 7868705 TI - Prenatal correlates of indigent mothers' attitudes about spoiling their young infants: a longitudinal study. AB - The purpose of this study was to investigate factors associated with indigent mothers' attitudes about spoiling their young infants. Mothers who believe that young infants can be spoiled may be more likely to misperceive their infants' basic needs for nurturing and thus undermine their infants' sense of security and trust. One hundred twenty-nine consecutive pregnant women who were at approximately 15 weeks' gestation completed measures to assess depressive symptoms (Center for Epidemiologic Studies Depression Scale) and social support (Maternal Social Support Index). One hundred seventeen mothers (91%) completed a simple three-question Spoiling Index when their infants were about 1 month old. Fifty-eight percent were single, never married, 73% multiparous, 66% Euro American, 28% African-American, and 84% at least 20 years old. Fifty-eight percent of mothers believed infants younger than 5 months old could be spoiled. After including maternal age, race, marital status, prenatal social support, and number of prenatal clinic visits in the hierarchical logistic regression model, "spoilers" were more likely to be primigravida mothers (odds ratio = 2.71; 95% confidence interval, 1.05 to 7.06) and more likely to be depressed during pregnancy (odds ratio = 2.83; 95% confidence interval, 1.29 to 6.19). Primigravida indigent mothers and mothers with higher levels of prenatal depressive symptoms are more likely to believe they can spoil their young infants. PMID- 7868706 TI - Behavioral toilet training in early childhood: research, practice, and implications. AB - The process of toilet training children has received surprisingly little attention in the medical research literature, and many parents may welcome guidance from their physician on how best to carry out this important parental duty. Theory and prescription for toilet training in the United States since 1900 has traced a pendulum's path between the polar opposites of passive permissiveness and systematic control. Since midcentury, the trend in the United States has been toward delayed toilet-training, typically between the child's second and third year. Like all trends, however, this one may reverse. Given children's developmental differences, a new trend toward early toilet training, if it emerges, may be accompanied by an increase in toilet-training problems. If so, physicians who advise parents and treat pediatric populations may wish to become more familiar with data-based behavioral management of toilet training and the implications of this approach for early toilet training and the treatment of toileting-refusal behavior. PMID- 7868707 TI - The parent-infant bonding controversy: a critique of the critics. PMID- 7868708 TI - The blind reading the blind. PMID- 7868709 TI - Lichen sclerosus. AB - Lichen sclerosus, usually appearing in the dermatologic literature under the names of lichen sclerosus et atrophicus, balanitis xerotica obliterans, and kraurosis vulvae, is an inflammatory disease with a multifactorial origin. A past association of lichen sclerosus and genital squamous cell carcinoma is not as close as once thought. Once considered primarily a surgical problem, especially when the genitals were involved, lichen sclerosus will respond to a variety of systemic and topical therapies. PMID- 7868710 TI - Drugs with antihistaminic properties as a cause of atypical cutaneous lymphoid hyperplasia. AB - BACKGROUND: Although an association between antihistaminic drugs and atypical cutaneous lymphoid infiltrates has not been reported previously, in vitro evidence suggests that these agents perturb certain lymphoid functions through binding to histamine receptors, including a novel growth-promoting intracellular histamine receptor, designated HIC. OBJECTIVE: We studied the clinical findings and histopathologic findings in 14 patients taking antihistaminic drugs in whom atypical cutaneous lymphoid infiltrates developed. METHODS: We retrospectively reviewed the clinical and histologic features of these patients' skin lesions. RESULTS: The clinical presentations included solitary or multiple nodules and plaques, and multiple papules. In some patients a temporal association between drug therapy and clinical course was observed, as the lesions improved or resolved after a decrease or discontinuation of the drug. Eleven patients were taking two or more medications that in vitro are associated with alterations in lymphocyte function, including agents without antihistaminic properties. A diagnosis of pseudolymphoma seemed clinically apposite in seven of the 14 patients on the basis of either resolution of the eruption or presentation of a solitary nodule that did not recur after excision. Histologic analysis showed four distinct morphologies: mycosis fungoides-like, nodular dermal infiltrates consistent with either lymphocytoma cutis or lymphoma cutis, lymphomatoid vascular reaction, and follicular mucinosis. Common to cases showing the first pattern were histologic features suggesting a delayed-type hypersensitivity reaction, thus enabling their distinction from mycosis fungoides. The infiltrates were predominantly of T-cell phenotype. CONCLUSION: Antihistamines are associated with atypical lymphoid hyperplasia in some patients. The antihistaminic drug may not be the provocative agent per se; rather, a drug-induced immunodysregulatory state may render an abnormal immune response to some other exogenous antigen. Multidrug therapy with these and other agents known to exert immunomodulatory effects may increase susceptibility to the development of atypical lymphoid hyperplasia and malignant lymphoma. PMID- 7868711 TI - Antifungal activity of itraconazole and terbinafine in human stratum corneum: a comparative study. AB - BACKGROUND: The evaluation of antifungal agents by in vitro and animal experiments cannot predict clinical efficacy with certainty. New models are needed to assess and compare antifungal activity. OBJECTIVE: We compared on human stratum corneum ex vivo the antifungal activity and lingering effect of 200 mg itraconazole daily and twice daily, and 250 mg/day terbinafine. METHODS: Three groups of 10 healthy volunteers entered the open comparative trial. Results were evaluated in a blinded manner. Cyanoacrylate skin surface strippings (CSSS) were taken from the back and superficial dermatome skin samples (SDSS) were taken from plantar skin at days 0, 1, 3, 7, 8, 10, 14, 21, 28, and 35. Spores or yeasts of selected fungi (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, and Candida albicans) were deposited and cultured on the CSSS and SDSS. The 1-week fungal growth on CSSS and SDSS was assessed over time by computerized image analysis to derive the inhibitory effect of the oral antifungal agents administered. Fungitoxic activity was also assessed by the use of 2-day cultures on CSSS followed by a transfer to Sabouraud medium. RESULTS: Comparable antifungal activity against dermatophytes was found for all three regimens. Itraconazole at both dosages was always significantly more active than terbinafine against C. albicans on CSSS and SDSS. Overall, 200 mg itraconazole twice daily appeared to be more fungitoxic than 250 mg/day terbinafine and 200 mg/day itraconazole. CONCLUSION: The ex vivo culture of fungi on human stratum corneum is very similar to the in vivo situation. Both itraconazole and terbinafine display high antidermatophyte activity. Faster onset and longer posttherapy activity were demonstrated in the itraconazole treatment groups. Terbinafine had marginal activity against C. albicans in this model. PMID- 7868712 TI - Risk of acquiring human papillomavirus from the plume produced by the carbon dioxide laser in the treatment of warts. AB - BACKGROUND: The documented presence of human papillomavirus DNA in the plume after carbon dioxide laser treatment of warts has raised questions about the risk of transmission of human papillomavirus to laser surgeons. OBJECTIVE: We sought to define more clearly the risks to surgeons of acquiring warts from the CO2 laser plume. METHODS: A comparative study was conducted between CO2 laser surgeons and two large groups of population-based control subjects (patients with warts in Olmsted County and at the Mayo Clinic from 1988 to 1992). Conclusions were drawn about the risks to surgeons of acquiring warts from the CO2 laser plume. RESULTS: There was no significant difference (p = 0.569) between the incidence of CO2 laser surgeons with warts (5.4%) and patients with warts in Olmsted County from 1988 to 1992 (4.9%). There was a significant difference between the incidence of plantar (p = 0.004), nasopharyngeal (p = 0.001), and genital and perianal warts (p = 0.004) in the study group and in patients with warts treated at the Mayo Clinic from 1988 to 1992. No significant difference was found between physicians who had acquired warts and those who were wart free, on the basis of the failure to use gloves (p = 0.418), standard surgical masks (p = 0.748), laser masks (p = 0.418), smoke evacuators (p = 0.564), eye protection (p = 0.196), or full surgical gowns (p = 0.216). Finally, the incidence rates of surgeons with warts per 1000 person-years did not increase significantly (p = 0.951) as the length of time that the CO2 laser was used to treat warts increased. CONCLUSION: When warts are grouped together without specification of anatomic site, CO2 laser surgeons are no more likely to acquire warts than a person in the general population. However, human papillomavirus types that cause genital warts seem to have a predilection for infecting the upper airway mucosa, and laser plume containing these viruses may represent more of a hazard to the surgeon. PMID- 7868713 TI - Accuracy of indirect immunofluorescence testing in the diagnosis of paraneoplastic pemphigus. AB - BACKGROUND: Paraneoplastic pemphigus (PNP) is an autoimmune disease defined in part by autoantibodies with unique specificity. Initial reports suggested that indirect immunofluorescence with rodent bladder epithelium was highly reliable in detecting these autoantibodies. OBJECTIVE: We compared the sensitivity and the specificity of indirect immunofluorescence in the diagnosis of PNP in a large number of cases. METHODS: Indirect immunofluorescence was performed on stratified squamous epithelium of monkey esophagus and mouse tongue, bladder, liver, and myocardium. Sera were obtained from 28 patients with PNP and from 29 control subjects with autoimmune blistering diseases. RESULTS: The sensitivity of murine bladder as a substrate was 75%, with a specificity of 83%. Indirect immunofluorescence on liver was specific (96.5%) but insensitive (43%). Sensitivity and specificity with myocardium were intermediate. CONCLUSION: Indirect immunofluorescence on murine bladder epithelium is an adequate screening test for PNP but is negative or indeterminate in as many as one fourth of patients. Negative indirect immunofluorescence does not exclude the diagnosis of PNP, and immunochemical techniques such as immunoprecipitation must be performed. PMID- 7868714 TI - CD8-positive tumor-infiltrating lymphocytes influence the long-term survival of patients with mycosis fungoides. AB - BACKGROUND: Nonneoplastic mononuclear cells commonly infiltrate lesions of mycosis fungoides. OBJECTIVE: We sought to determine the immunophenotypic characteristics of these cells and to determine whether the presence of CD8+ tumor-infiltrating lymphocytes has an impact on prognosis. METHODS: Skin biopsy specimens from 78 patients were stained with immunopleroxidase techniques to determine their phenotypic characteristics. The proportion of CD8+ tumor infiltrating lymphocytes was quantified and compared with stage of disease and survival rate. RESULTS: Patients with more limited T-stage disease tended to have a higher proportion of CD8+ cells in their skin biopsy specimens, compared with patients with more advanced T-stage disease. Within each T-stage patients with a larger proportion of CD8+ cells had a better survival rate than those with fewer CD8+ cells (p < 0.05 for T1 and T3). A multivariate analysis confirmed the importance of T stage (p = 0.0006), overall stage (p = 0.0112), and CD8 positivity (p = 0.0335) in this cohort of patients. CONCLUSION: CD8+ tumor infiltrating lymphocytes in mycosis fungoides correlate with improved survival rate and may exert an antitumor effect rather than being mere bystander cells. PMID- 7868715 TI - Vertical and transverse sections of alopecia biopsy specimens: combining the two to maximize diagnostic yield. AB - BACKGROUND: Traditional vertical sections of scalp biopsy specimens contain few hair follicles. For this reason transverse sections of scalp biopsy specimens have been advocated. Both methods have advantages and disadvantages. We have developed a simple method that we believe offers the best of both methods. OBJECTIVE: Our purpose was to assess the impact of combining vertical and transverse sections of scalp biopsy specimens. METHODS: Two 4 mm punch biopsies are performed. One specimen is bisected vertically: half for hematoxylin-eosin (H E) staining, half for direct immunofluorescence. The second specimen is bisected transversely and submitted for H-E. The three pieces of tissue for H-E staining are embedded in a single cassette. RESULTS: Because a biopsy specimen for direct immunofluorescence is commonly obtained in cases of alopecia, our method does not add a surgical procedure. All three pieces of tissue for H-E staining are embedded in a single paraffin block. Therefore the cost of histologic interpretation is not increased. Our diagnostic yield improved. Transverse sections were superior in cases of lupus erythematosus and lichen planopilaris with focal follicular involvement. Features of the follicular degeneration syndrome were also best demonstrated in transverse sections. Interface changes, lupus panniculitis, miniaturized hairs, and trichomalacia were better demonstrated in vertical sections. CONCLUSION: Our method exploits the advantages of both vertical and transverse sections and improves diagnostic yield without increasing cost. PMID- 7868716 TI - Skin cancer in heart transplant recipients. AB - BACKGROUND: The frequency of skin cancer in organ transplant recipients is high, up to 15%. OBJECTIVE: Our purpose was to determine the incidence of skin cancer in patients who underwent immunosuppression after heart transplantation and to determine the factors important in the appearance of skin cancer. METHODS: We studied the frequency of skin cancer in 92 of 111 patients after they underwent heart transplantation between January 1984 and December 1993. RESULTS: At least one cutaneous neoplasm (squamous cell carcinoma and/or basal cell carcinoma) developed in 14 patients (15.2%). The basal cell carcinoma to squamous cell carcinoma ratio was 1:1.5. The skin cancer appeared an average of 31.5 months after transplantation; the average was 36 months for squamous cell carcinoma and 25.3 months for basal cell carcinoma. Cumulative risk rose from 4.3% at 1 year up to 43.8% at 7 years after transplantation. The overall incidence of both types of skin cancer was 45.3 per 1000 posttransplant person-years, with an incidence of 25.8 for basal cell carcinoma and 29.1 for squamous cell carcinoma. Most skin cancers developed between 2 and 3 years after transplantation. All patients were exposed to a significant amount of ultraviolet radiation and had skin type II or III. We did not find a significant association between skin cancer and haplotype HLA-A3, HLA-A11, HLA-DR, and the number of mismatches for HLA-B. CONCLUSION: We found an increased progressive cumulative incidence of skin cancer in heart transplant recipients for two reasons: (1) immunosuppression and increased exposure to ultraviolet radiation in some patients, and (2) the skin type of certain patients. We emphasize the need for photoprotection in this group of patients and regular skin cancer screening examinations. PMID- 7868717 TI - Secondary amyloidosis complicating psoriasis. AB - BACKGROUND: Amyloidosis is a heterogeneous group of disorders characterized by extracellular deposition of fibrillar protein. Secondary amyloidosis occurs in patients with chronic infectious or inflammatory processes. Only 18 cases of secondary amyloidosis complicating psoriasis have been reported. OBJECTIVE: We characterized secondary amyloidosis complicating psoriasis. METHODS: We reviewed all cases of coexisting psoriasis and amyloidosis seen at the Mayo Clinic from 1950 to 1992. The clinical characteristics were summarized, and the literature was reviewed. RESULTS: There were 28 cases of coexistent disease, and in five of these psoriasis was the only inflammatory condition preceding the development of secondary amyloidosis. Histopathologic confirmation with Congo red staining was available in four cases, and immunohistochemical confirmation of the characteristic amyloid A subtype was performed in two. CONCLUSION: Follow-up of four patients supports the view that amyloidosis associated with psoriasis is an aggressive disease that may be fatal. PMID- 7868718 TI - Effects of topical preparations on the erythemogenicity of UVB: implications for psoriasis phototherapy. AB - BACKGROUND: Topical preparations are sometimes applied before phototherapy without consideration of their potential to block UVB. OBJECTIVE: Our purpose was to examine the ability of topical preparations to block UVB. METHODS: Volunteers pretreated with mineral oil, a clear liquid emollient, 5% crude coal tar, 6% salicylic acid ointment, emollient creams, and petrolatum underwent minimal erythema dose testing. Transmission of UVB through a clear film coated with the preparations was measured. RESULTS: Tars and salicylic acid blocked UVB. Thick application of petrolatum and emollient creams can reduce transmission of UVB. Mineral oil and a clear liquid emollient did not significantly affect transmission or erythemogenicity of UVB. CONCLUSION: Clear liquid emollient and mineral oil can be used before phototherapy. If not removed before phototherapy, preparations containing tar or salicylic acid, or thickly applied petrolatum or emollients, can block UVB and presumably reduce its efficacy in the treatment of psoriasis. PMID- 7868719 TI - Pilot histologic and ultrastructural study of the effects of medium-depth chemical facial peels on dermal collagen in patients with actinically damaged skin. AB - BACKGROUND: Chemical peels are employed for a variety of benign and premalignant skin disorders. OBJECTIVE: We compared clinical and histologic features with ultrastructural changes that occur after medium-depth chemical facial peel. METHODS: Three men with actinically damaged facial skin underwent a single 35% trichloroacetic acid peel. Biopsy specimens were taken before the peel, and 2 weeks and 3 months after the peel, for histologic examination, electron microscopy, and gel electrophoresis to assess total collagen type I content. RESULTS: Clinical resolution of actinic damage corresponded with restoration of epidermal polarity. Collagen type I was markedly increased after the peel. Characteristic ultrastructural features of skin after peeling include markedly decreased epidermal intracytoplasmic vacuoles, decreased elastic fibers, and increased activated fibroblasts. CONCLUSION: Electron microscopic studies after a medium-depth chemical peel of photodamaged skin reveal more profound changes than those seen histologically. PMID- 7868721 TI - Dermatology '94--in the eye of a hurricane. 1994 Clarence S. Livingood Lecture, American Academy of Dermatology. PMID- 7868720 TI - Atypical mole syndrome: risk factor for cutaneous malignant melanoma and implications for management. AB - The incidence of malignant melanoma is increasing faster than that of any other cancer. It is important to identify subsets of the population at high risk of its development so that they can be observed more closely to identify early melanomas when they are curable. It has been reported worldwide that persons with the atypical mole (dysplastic nevus) syndrome are such a subset at increased risk. A risk gradient for the development of melanoma exists and varies from persons with one or two atypical moles and no family history of melanoma at one end of the spectrum to persons with the familial atypical multiple-mole melanoma syndrome at the other. Guidelines for the management of atypical mole syndrome are presented. PMID- 7868722 TI - Clinical pearl: diagnosis of onychomycosis. PMID- 7868723 TI - The Swedish pimple. Or, thoughts on specialization. PMID- 7868724 TI - Bacillary angiomatosis of the skin and bone marrow in a patient with HIV infection. PMID- 7868725 TI - Porphyria cutanea tarda in hepatitis C virus-infected blood donors. PMID- 7868726 TI - Ciliated cyst of the vulva. PMID- 7868727 TI - Dyshidrosiform pemphigoid. PMID- 7868728 TI - Treatment of cutaneous leishmaniasis with allopurinol. PMID- 7868729 TI - Lymphoma en cuirasse. PMID- 7868730 TI - Congenital lower lip pits (Van der Woude syndrome). PMID- 7868731 TI - Reactive perforating collagenosis of diabetes mellitus. PMID- 7868732 TI - Spiny hyperkeratosis of the fingers as an unusual sign of epidermodysplasia verruciformis. PMID- 7868733 TI - Thrombocytopenia caused by fluconazole therapy. PMID- 7868734 TI - Paradoxical coexistence of contact dermatitis and anergy in a man with AIDS. PMID- 7868735 TI - Congenital constriction bands: amniotic band syndrome. PMID- 7868736 TI - Antifungal agents. PMID- 7868737 TI - Antibiotic treatment in women taking oral contraceptives. PMID- 7868738 TI - Hepatitis C and its association with lichen planus and porphyria cutanea tarda. PMID- 7868740 TI - Dermal suturing technique. PMID- 7868739 TI - Pentoxifylline for Sweet's syndrome. PMID- 7868741 TI - Nursing faculty development during a time of declining resources. AB - During a time of declining resources, a school of nursing faculty development committee and their Dean devised a way to provide need-specific scholarly development programs using principles of human potential development. The process yielded information useful for faculty development, regardless of economic resources. Faculty were invited to participate in a non-confidential survey that assessed their needs for scholarly productivity, resources they would offer to others, and goals for their own development. The list of resources and needs generated was shared with faculty. Based upon the needs and resources identified, specific development activities were initiated. Six workshops were planned and implemented with high (89%) participation. The dean hired a part-time statistician, a faculty member developed and distributed a handout on "Tips for Time Management," and a writers' support group was formed. This approach to faculty development merits consideration by other groups since it focuses upon the synergistic development of human potential. PMID- 7868742 TI - Distance education programs: defining issues of assessment, accessibility, and accommodation. AB - Identification and resolution of a variety of issues is imperative to establishing effective distance education via telecommunications. In this first hand experience, the authors describe selected issues and possible responses inherent in the development and implementation of a new teaching modality. The decision to pursue distance education by telecommunications should be made only after a thorough examination of the needs, the required resources, and the changes to be expected. Advance planning is essential for problem solving. PMID- 7868743 TI - Basic academic preparation of foreign-educated nurses: a base for developing continuing education courses. AB - This international investigation was conducted to determine curricular factors that may explain the high failure rate on the Nurse Certification Licensure Examination for Registered Nurses (NCLEX-RN) of foreign-educated nurses (FENs) seeking licensure in the United States. The framework was the existence of basic knowledge as a starting point for adapting and modifying practices (Alfano, 1971). Onsite visits were used to conduct a curricular review of basic academic preparation of FENs at 19 nursing programs in 10 selected countries. Curricular factors found common to all schools and country-specific elements may explain the academic difficulties of FENs relative to licensure and nursing practice. Delineated curricular elements discussed can serve as a base for developing continuing education courses for foreign-educated nurses. PMID- 7868744 TI - Videotape intervention: producing videotapes for use in nursing practice and education. AB - The purpose of this article is to describe the process utilized to produce nursing-specific videotapes for application in clinical or educational settings. The three phases, pre-production, production and post-production, are exemplified with the description of the process used by the authors as they developed the Nurseline Video-Assisted Modeling Program (NuVAMP), a video intervention for caregivers of people with dementia that helps them to shape family members' behaviors in activities of daily living. The practical aspects of video production are emphasized, including script writing, budget development, and the video editing process. PMID- 7868745 TI - Outcomes of nurse (RN) refresher courses in a midwestern city. AB - Graduates of RN refresher courses offered by three hospitals in a midwestern city from 1981 to 1991 were surveyed (N = 179) to compare the nurses who returned to work (n = 148, 82.7%) with those who did not return to work (n = 26, 14.5%) on demographic and career characteristics, personal responsibilities, and attitudes toward professional nursing (5 nurses [2.8%] did not respond to this item). The non-returning group had fewer mean years of experience prior to leaving nursing, more mean years since last nursing position, and lower mean scores on the Professional Attitude scale used in this study, but the differences were not statistically significant. PMID- 7868746 TI - Teaching strategies to promote critical thinking skills in nursing staff. AB - The promotion of critical thinking skills necessary for safe, effective, state-of the-art nursing care is discussed in this article. Definitions of critical thinking and inductive and deductive reasoning are explored. Benner's (1986) research, based on Dreyfus and Dreyfus' (1980) model of skill acquisition, provides a basis for the various strategies mentioned to teach critical thinking. Implementation and evaluation of these strategies are addressed. PMID- 7868747 TI - How do you want to improve yourself? Nursing education administration and faculty attitudes toward types of faculty development. AB - The purpose of this study was to survey the perceived effectiveness of: (1) on campus workshops, (2) off-campus workshops, (3) consultations, (4) leaves, (5) grants, (6) courses or seminars, and (7) special assignments for the faculty development of academic roles of nursing faculty. Faculty roles considered were: (1) classroom teaching, (2) clinical teaching, (3) research, (4) service to the institution, (5) community service, and (6) leadership. The samples of the study included 12 nursing administrators and 105 full-time and part-time faculty of the 13 nursing programs in the City University of New York (CUNY). Faculty development grants were rated highest by both administrators and faculty members. Both rated off-campus workshops second. Administrators and faculty perceived developmental activities in the area of research as most effective, followed by classroom teaching, clinical teaching, leadership, service to the institution, and community service. Faculty perceptions of the effectiveness of the seven techniques of faculty development were uniformly higher than administrator perceptions. Faculty members perceived development for classroom teaching, clinical teaching, and service to the institution more positively than did administrators. PMID- 7868748 TI - Acute cutaneous eruptions after marrow ablation: roses by other names? AB - This review will cover acute cutaneous eruptions following marrow ablation in the treatment of various malignant neoplasms. The clinical and histopathological features of 1. the eruption of lymphocyte recovery, 2. acute allogeneic graft-vs host reaction, 3. acute autologous (spontaneous) graft-vs-host reaction, 4. eruptions associated with the administration of cyclosporin A, and 5. eruptions associated with the administration of human recombinant cytokines in pharmacologic doses will be considered. The idea is put forth that the second, third, and fourth cutaneous eruptions listed above represent variations on the theme of the eruption of lymphocyte recovery. The final common pathway in the development of all these diffuse erythematous eruptions probably relates to the elaboration of cytokines by infiltrating lymphocytes or to the administration of cytokines in pharmacologic doses. PMID- 7868749 TI - Immunohistochemical expression of BCL-2 in melanomas and intradermal nevi. AB - The BCL-2 gene is the prototype of a newly described family of oncogenes involved in tumorigenesis by blocking apoptosis, or programmed cell death. Overexpression of BCL-2 protein was originally described in follicular B-cell lymphomas bearing the 14;18 translocation. BCL-2 overexpression has also been described in other lymphomas and more rarely in neoplasms outside the lymphoid tissue. The aim of this paper is to determine the immunohistochemical expression of BCL-2 in intradermal nevi and primary invasive and metastatic melanoma. Formalin-fixed and paraffin-embedded tissues from 4 cutaneous melanoma metastases, 10 primary invasive melanomas, and 10 intradermal melanocytic nevi were immunolabeled with monoclonal antibodies directed against BCL-2 protein (Dako, clone 124) and Ki-67 antigen (Amac, clone MIB-1), after antigen retrieval techniques. Morphologically normal epidermal melanocytes expressed BCL-2, as did nevi and melanomas in virtually all cells. However, whereas the labeling in normal melanocytes and nevus cells showed a uniformly strong reactivity, melanoma cells showed a variable but mainly weak reactivity. Ki-67 antigen expression was restricted to melanomas. The widespread expression of BCL-2 suggests that this oncoprotein cannot be involved in the malignant transformation of melanocytic cells. It seems likely that the decreased BCL-2 expression detected in melanomas may reflect one further step of tumor progression in melanocytic neoplasms. PMID- 7868750 TI - Aberrant bcl-2 protein expression provides a possible mechanism of neoplastic cell growth in cutaneous basal-cell carcinoma. AB - The bcl-2 proto-oncogene encodes a protein that protects cells from programmed cell death (apoptosis). High levels of this protein confer a growth advantage to neoplastic cells even in the absence of a high mitotic rate. This gene is involved in the interchromosomal 14;18 translocation, an abnormality present in more than two-thirds of follicular lymphomas and in about 25% of other non Hodgkin's lymphomas of the lymph nodes. A recent study also demonstrated the presence of high levels of bcl-2 protein in solid tumors such as squamous cell carcinomas of the lung and related it to a better prognosis. We analyzed bcl-2 protein expression in 20 cases each of basal- and squamous-cell carcinoma and in 5 biopsy specimens of normal skin, using a monoclonal anti-bcl-2 protein antibody with a standard 3-step immunoperoxidase technique on routinely fixed, paraffin embedded tissue sections. Normal skin showed positive staining of the majority of keratinocytes in the epidermal basal layer. Bcl-2 positivity was also observed within the outer root sheath and the mesenchymal cells of the follicular papillae, the clear cells of the eccrine glands, and in some melanocytes at the dermo-epidermal junction. Neoplastic cells in all cases of basal-cell carcinoma showed a positive cytoplasmic reaction for bcl-2. All biopsy specimens of squamous-cell carcinoma were negative. Expression of bcl-2 protein could also be observed in the majority of peri- and intratumoral lymphocytes in both basal-cell carcinoma and squamous-cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868751 TI - Aneuploidy in atypical fibroxanthoma: DNA content quantification of 10 cases by image analysis. AB - It has recently been reported that atypical fibroxanthoma (AFX) is a predominantly diploid lesion in contrast to malignant fibrous hystiocytoma (MFH) which is usually aneuploid. To test this hypothesis, DNA content quantification was undertaken on Feulgen-stained cytology and tissue section preparations from 10 cases of AFX by image analysis. The large atypical cells which characterize AFX were aneuploid in each case. Smaller spindle-shaped cells found in this lesion were diploid. The results suggest that AFX is indistinguishable from MFH by DNA content estimation and highlight an advantage of image analysis over flow cytometry. PMID- 7868752 TI - Examination of non-involved skin, previously involved skin, and peripheral blood for herpes simplex virus DNA in patients with recurrent herpes-associated erythema multiforme. AB - The association between infection with HSV and the subsequent development of erythema multiforme is well established, although the role that the virus plays in the pathogenesis of this disorder is not known. HSV DNA has been detected in cutaneous lesions of herpes-associated erythema multiforme (HAEM), and it has been suggested that the tissue damage seen in these lesions is virus-specific. In the current, prospective study, we examined biopsies of lesional, non-involved, and previously involved but healed skin, in addition to specimens of peripheral blood, from patients with HAEM, for HSV DNA by using the polymerase chain reaction. HSV DNA was detected in lesional skin of 10 of 11 patients compared to 2 of 11 non-involved skin biopsies obtained at the same time. HSV was present in 4 of 6 blood specimens obtained during the acute episode. Five patients returned 3 months after the acute episode resolved for biopsies of previously involved skin. HSV was detected in 4 of these 5 biopsies. Thus, the presence of HSV DNA in the skin of patients with HAEM appears to be predominantly in areas of clinical involvement; the virus remains in those cutaneous sites for up to 3 months without evidence of clinical disease; and HSV DNA may be detected in the peripheral blood cells during acute HAEM. Based on these findings, we suggest that the virus plays a role in lesion development, that the skin may function as a site of viral persistence, and that hematogenous spread of viral DNA may be an important factor in the development of HAEM. PMID- 7868753 TI - T lymphocytes bearing the gamma/delta T-cell receptor in cutaneous lesions of dermatitis herpetiformis. AB - T lymphocytes bearing the gamma/delta T-cell receptor are a rare component of normal human GI epithelium and skin. Recently, however, an unusually high percentage of T lymphocytes with gamma/delta receptors has been described in gastrointestinal biopsies from patients with dermatitis herpetiformis, implicating the gamma/delta T cell subset in the pathogenesis of this disease. We investigated a possible role for this subset of lymphocytes in the pathogenesis of the cutaneous lesions of dermatitis herpetiformis. Using a standard immunoperoxidase technique, we labelled perilesional skin biopsies from patients with dermatitis herpetiformis and other inflammatory dermatoses with monoclonal antibodies to CD3, CD4, CD8, alpha/beta T cell receptor, gamma/delta T cell receptor, and IL-2 receptor. We found no differences in the percentage of gamma/delta positive T lymphocytes in skin lesions of dermatitis herpetiformis as compared to other selected inflammatory conditions. These findings suggest that the pathogenesis of the cutaneous lesions of dermatitis herpetiformis is not mediated through gamma/delta T cells, and that the cutaneous lesions may develop through mechanisms different from those operative in the gastrointestinal tract. PMID- 7868754 TI - Histopathology in erythroderma: review of a series of cases by multiple observers. AB - This study examines the utility of objective histopathological studies in the evaluation of adult patients with erythroderma. A series of 56 skin biopsies, from 40 erythrodermic patients, was reviewed sequentially by 4 Canadian dermatopathologists who were unaware of clinical details of the cases. The final diagnosis (gold standard), in each instance, had already been determined by others, based on clinicopathologic data and response to therapy. Direct comparison revealed that the mean accuracy of the histopathological diagnoses was 53% (range: 48-66%), a favorable result in view of the difficulty of the task at hand. Additional points of information which evolved from the study are as follows: (i) identification, by microscopy alone, of spongiotic dermatitis, cutaneous T-cell lymphoma and psoriasis, as underlying causes of erythroderma was more successful than that of drug eruptions and pityriasis rubra pilaris; (ii) the epidermotropism which characterizes cutaneous T-cell lymphoma may be mistaken for inflammatory interface changes seen in drug eruptions and vice versa, thus constituting a pitfall in diagnosis; (iii) finally, it appears that submission of multiple simultaneous biopsies, rather than a single specimen, from patients with erythroderma would be likely to enhance the accuracy of histopathological diagnosis. PMID- 7868755 TI - Immunohistochemical analysis of dermal mononuclear cell infiltrates in cutaneous lupus erythematosus, polymorphous light eruption, lymphocytic infiltration of Jessner, and cutaneous lymphoid hyperplasia: a comparative differential study. AB - Cutaneous lupus erythematosus (LE), polymorphous light-eruption (PMLE), lymphocytic infiltration of Jessner (LIJ), and cutaneous lymphoid hyperplasia (CLH) are often difficult to differentiate from one another by light microscopic examination. We conducted an immunohistochemical analysis of the mononuclear cell infiltrates in 13 LE, 12 PMLE, 10 LIJ, and 13 CLH with various antibodies. Antibodies L26, UCHL1, and S100 achieved statistically significant differences among the four diseases, but because of the overlaps in the number of UCHL1(+) T cells and S100 protein (+) cells in individual cases, these two antibodies were not useful. Only CLH could be distinguished from LE, PMLE, and LIJ by a greater number of CD20(+) B cells. The latter three conditions could not be differentiated. Contrary to previous reports, plasmacytoid-monocytes were not found to be increased in LIJ for the differentiation of the latter from LE and PMLE. Our results support the conclusion that CLH is a reactive lymphoid hyperplastic process with proliferation of both B and T cells, whereas the T cell was the predominant cell type in the infiltrates of LE, PMLE, and LIJ, indicating that they were related to T cell disorders. The histiocyte was only a minor component cell. The plasmacytoid monocyte in general was not significantly present in all four conditions, but relatively more plasmacytoid monocytes were present in CLH. PMID- 7868756 TI - The spectrum of cutaneous granulomatous vasculitis: histopathologic report of eight cases with clinical correlation. AB - Cutaneous granulomatous vasculitis is an uncommon histopathologic finding that has been associated with lymphoproliferative disorders, systemic vasculitis, autoimmune inflammatory diseases, and infection. To define further the concept of cutaneous granulomatous vasculitis and to emphasize its clinical importance, we reviewed biopsy material from 8 patients seen from 1985 through 1992. All biopsies showed evidence of blood vessel damage with fibrinoid change or hemorrhage (or both) and granulomatous inflammation in and around vessel walls. Special stains for microorganisms were negative in all cases. Associated medical disorders included neuropathy (2 patients), sarcoid-like disease (2), systemic vasculitis (1), lymphoma and suspected lymphoma (1 each), and associated herpes simplex virus (1). T-cell gene-rearrangement studies were negative in a patient with suspected lymphoma. Granulomatous cutaneous vasculitis is most commonly associated with lymphoma and systemic vasculitis. In selected cases, infection should be considered as an underlying cause. PMID- 7868757 TI - A case of acantholytic dermatosis of the vulva with features of pemphigus vegetans. AB - We report an unusual case of vulvar acantholytic dermatosis with features of pemphigus vegetans in a 22-year-old Indian girl who presented with a "warty" lesion in her left labium majus. Following excision of this lesion, she presented with 2 localized recurrent lesions on the left and right labia majora about 2 1/2 years later which were also excised. All 3 biopsies showed histological features typical of pemphigus which included extensive suprabasal acantholysis with bullae formation, prominent villus-like processes at the base of the bullae, focal hyperkeratosis and papillomatosis, and the occasional mixed neutrophil and eosinophilic intraepidermal abscess. IgG and C3 immunofluorescence was positive in the intercellular spaces of the epidermis. These lesions, which probably represent a form of pemphigus vegetans, have not been previously reported as a cause of localized vulvar acantholytic dermatosis. PMID- 7868758 TI - Hyperplastic pacinian corpuscles: an uncommonly encountered lesion of the hand. AB - The occurrence of hyperplastic pacinian corpuscles in the hand is rare, with only 13 cases reported in the literature. We describe such a case in a 70-year-old male who had worked as a locksmith for many years. A grape-like cluster of firm, rice-sized nodules was discovered in the subcutaneous tissue of the finger following a glass-induced injury. Histopathological findings revealed pacinian corpuscles to be increased in size and number. Individual corpuscles consisted of a central nerve fiber surrounded by 35 to 60 concentric lamellae (normal controls from other specimens: 13-15 lamellae). The external corpuscular diameter ranged from 1.8 to 3.2 mm (normal controls from other specimens: 1.6 mm). Immunohistochemistry showed positive staining with Leu 7 antibody and antiglial fibrillary acidic protein in the small nerves situated in the vicinity of the pacinian corpuscles, but not in the corpuscles themselves. The lesion reported here clearly differed from both neurofibroma with occasional pacinian differentiation and the so-called pacinian neurofibroma. There was no evidence of neurofibromatosis. PMID- 7868759 TI - Tufted angioma with complete regression. AB - We describe 2 patients with tufted angioma (angioblastoma of Nakagawa) which regressed spontaneously. Both patients had a solitary but large lesion on the trunk. The 1st patient, a 3-month-old girl, presented with a 6-cm plaque which began to regress 2 years later. It regressed completely over 1 year and had not recurred after a further 6-year follow-up. The other patient, a 3-month-old boy, presented with a 12-cm mass of coalescent angiomatous papules which slowly regressed over 3-years, while small new lesions appeared in the adjacent contiguous skin. Eventually, gradual and near complete regression was observed after 8 years. The histology in both cases was typical, but bore some resemblance to the recently described kaposiform hemangioendothelioma, lobular capillary hemangioma and spindle cell hemangioendothelioma. PMID- 7868760 TI - Multiple perifollicular fibromas: report of a case and analysis of the literature. AB - Perifollicular fibroma is a cutaneous hamartomatous proliferation of the pilar connective tissue sheath. We describe a patient with multiple perifollicular fibromas and analyze the literature on this topic. Histologically, perifollicular fibroma is characterized by a concentric arrangement of collagen fibers surrounding a generally unaltered hair follicle. Clinically, it is usually multiple and occurs predominantly on the face and upper trunk. This clinical presentation is similar to that observed in patients with the Birt-Hogg-Dube syndrome where, in addition to perifollicular fibromas, fibrofolliculomas, trichodiscomas, and acrochordons are found. Several reports of multiple perifollicular fibroma prior to the recognition of this syndrome may, in fact, represent cases of the Birt-Hogg-Dube syndrome. PMID- 7868761 TI - Determining the processing cost of a skin biopsy specimen. AB - An integral part of directing a pathology laboratory is to understand the nature and behavior of relevant costs. Until recently, pathologists did not need to accurately know the specific costs assigned to various steps in the processing of tissue specimens. With the advent of a more competitive approach to the delivery of health care, laboratory directors must accurately cost their product in order to use competitive pricing strategies. In this article, I review the principles that are used to analyze costs that are identified in a typical dermatopathology laboratory. PMID- 7868762 TI - Cutaneous papillary squamous cell carcinoma in an immunosuppressed host. PMID- 7868763 TI - Percentage errors. PMID- 7868764 TI - Unique and uncommon skin signs of systemic diseases. PMID- 7868765 TI - Evaluation of the Japanese-Chinese herbal medicine, kampo, for the treatment of lupus dermatoses in autoimmune prone MRL/Mp-lpr/lpr mice. AB - Kampo, a Japanese-Chinese traditional herbal medicine, has been used for the treatment of various diseases for about 3,000 years in China. Among herbal medicines, Sairei-to is well known for improving the symptoms of rheumatoid arthritis (RA) and other collagen diseases. However, its immunosuppressive effects on autoimmune cutaneous phenomena are not completely understood. We investigated the effects of Sairei-to on the development of lupus dermatoses in autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mice, an animal model which spontaneously develops skin lesions similar to those seen in human lupus erythematosus. Virgin female MRL/lpr mice at 1 month of age, which were treated orally with Sairei-to, had reduced amounts of IgG deposition at the dermoepidermal junction, titers of anti-DNA antibodies and rheumatoid factor, and lymphoproliferation. These results support the use of traditional herbal medicines in patients with human RA and systemic lupus erythematosus. PMID- 7868766 TI - Functional morphology of lesions of psoriasis vulgaris transplanted into nude mice at an early stage. AB - We examined the growth and differentiation of transplanted psoriatic skin in nude mice at an early stage. Psoriatic lesions from three patients were biopsied. Each biopsied specimen was cut into five blocks, which were individually transplanted to nude mice by the embedding method. Two weeks later, growth and differentiation of transplanted specimens were examined by bromodeoxyuridine (BrdU) labelling method and by electron microscopy. Electron microscopically, basal cells were longitudinally high, and the cellular processes were elongated. Basal laminae were multilayered. In the cytoplasm of the basal cells, many mitochondria, endoplasmic reticula, and ribosomes were seen, and tonofibrillar formation was poor. In cell groups in the upper parts of these lesions, both nuclei and cytoplasm showed degeneration. Psoriatic skin transplanted to nude mice exhibited newly formed psoriatic skin and initial epidermal necrosis. The BrdU labelling method labelled cells scattered in the lower part of the epidermis. Psoriatic skin transplanted to nude mice resembled that before transplantation in both ultrastructural findings and growth pattern. PMID- 7868767 TI - Proliferating cell nuclear antigen (PCNA) and p53 protein expression in Bowen's disease. AB - Bowen's disease is a premalignant dermatosis comprised of a clonal proliferation of atypical keratinocytes in the full thickness of the epidermis. To elucidate the relationship between the alteration of the p53 tumor suppressor protein and cell proliferation rate, we immunohistochemically examined the expression of proliferating cell nuclear antigen (PCNA) and p53 protein in 30 cases of Bowen's disease. All the cases exhibited the full-thickness distribution of PCNA-positive cycling cells in the lesional epidermis. Quantitation of PCNA staining by image cytometry revealed a mean labeling index (LI) of 75.1 +/- 20.3. p53 expression was detected in 13 cases (43%). Expression was diffuse (p53 LI > 50) in 9 cases, but focal (p53 LI < 30) in the other four. The mean PCNA LI of p53 diffusely positive cases was significantly greater than that of both p53 focally positive and p53 negative cases (89.3 +/- 10.1 vs 62.7 +/- 21.2, and 70.5 +/- 21.6; p < 0.01, respectively). These findings suggest that a high-level accumulation of p53 protein results in a more increased cell proliferation in Bowen's disease. PMID- 7868768 TI - Prognostic evaluation of cutaneous malignant melanoma based on the pTNM classification. AB - The prognoses of 100 consecutive melanoma patients were analyzed on the basis of Breslow's thickness and Clark's levels as well as according to stage employing the 1987 UICC pTNM classification. Among patients with lesions < or = 1.50 mm thick, the 10-year survival rate was 100% for both pT1 (n = 13) and pT2 (n = 6) disease, 73.4% for pT3a disease (n = 26), 62.2% for pT3b disease (n = 15), 69.3% for pT3 (n = 41) disease, and 38.7% for pT4 disease (n = 38). Significant differences in survival were found between the pT4 group and the pT1/pT3a or pT3 groups. The 10-year survival rate was 100% for level II (n = 13) and level III (n = 13) disease, 58.3% for level IV (n = 46) disease, and 34.5% for level V (n = 26) disease. Significant differences were found between level V and other levels. The survival rate at 10 years was 100% for stage I (n = 18), 63.3% for stage II (n = 24), and 52.5% for stage III (n = 55). In stage IV (n = 3), there was only one patient who survived for 42 months. There were significant differences in survival among all stages except I and II. The 10-year survival rate in 3 subgroups of stage III was 58.9% for pT4pN0M0 patients (n = 14), 63.2% for pT,pN1M0 patients (n = 31), and 20% for pT,pN2M0 patients (n = 10). Significant differences were found between the pT,pN1M0 and pT,pN2M0 subgroups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868769 TI - A case report of infiltrating ductal carcinoma originating from aberrant breast tissue. AB - We report a case of carcinoma originating from aberrant breast tissue in a 32 year-old female who had a soft subcutaneous mass on the anterior axillary fold. Histopathologic examination showed an infiltrating ductal carcinoma of aberrant breast tissue without metastasis to lymph nodes. We believe that subcutaneous nodules of uncertain origin around the periphery of the breast and especially in the axilla should always be viewed with suspicion and treated by early excision. PMID- 7868770 TI - Minocycline hydrochloride hyperpigmentation complicating treatment of pyoderma gangrenosum. AB - Minocycline-associated hyperpigmentation is an uncommon side effect. We report the case of a patient with pyoderma gangrenosum successfully treated with oral minocycline but complicated by marked hyperpigmentation in his pyoderma gangrenosum and acne scars. One of the clinical forms of minocycline hyperpigmentation includes dark-blue or black macules in depressed acne scars or other sites of skin inflammation; this pattern seems to be independent of the total cumulative dose and the skin process. PMID- 7868771 TI - Conversion of antinuclear antibody specificity as a marker of deterioration of cutaneous lupus erythematosus into lupus nephritis. AB - A 34-year-old male systemic lupus erythematosus patient (SLE) with cutaneous vasculitis developed renal failure after switching anti-nuclear antibody (ANA) specificity. He developed cutaneous lupus erythematosus with homogeneous and speckled type ANA and a high titer of anti-DNA antibody without renal involvement at 21 years of age. After developing lupus nephritis at the age of 27, the original ANA disappeared gradually. Two years later, a discrete speckled type ANA titer elevated abruptly to as high as 1:640 with low complementemia and without DNA antibody. Within five years, he suffered renal failure. This case of SLE suggests a direct correlation with ANA pattern and organ involvement. PMID- 7868772 TI - A case of cutaneous infection by Exophiala jeanselmei. AB - A case of cutaneous infection by Exophiala jeanselmei is reported. The patient was a 45-year-old Japanese female. Her skin eruption consisted of a group of erythematous papules on her left cheek to which corticosteroid had been topically applied for nearly 10 years. Histopathologically, a granuloma formation was noted in the dermis within which were many brown spores. The isolated fungus was identified as Exophiala jeanselmei. PMID- 7868773 TI - Oral florid papillomatosis and leukoplakia of the esophagus associated with keratoderma and showing transepidermal elimination. AB - A 37-year-old male presented with a cauliflower-like tumor in the right buccal mucosa, leukoplakia of the tongue and esophagus, and keratotic papules or plaques on the extremities including bilateral palms and soles, associated with borderline diabetes mellitus and a repeated history of infections. A multi-system keratinizing abnormality was suspected, although no distinct disease category has been found showing similar involvements. PMID- 7868774 TI - Calcification of eccrine poroma. AB - Two cases of eccrine poroma with calcification were described, both of which were those of the Winkelmann-MacLeod type. They occurred on the face and lower leg. We supposed that calcification in both cases was dystrophic in nature due to minor pressure or injury. The feature of calcification within the nests of eccrine poroma has rarely been reported. However, it seemed to be physiologically consistant that calcification occurs in eccrine poroma which originates from eccrine sweat glands. PMID- 7868775 TI - Healing of chronic atopic dermatitis lesions in skin areas of paraplegia after trauma. AB - A case of atopic dermatitis in a 12-year-old boy with spontaneous clearing of skin lesions in areas of paraplegia after trauma is reported. This observation might confirm the important pathogenetic role of neuropeptides in the development of atopic dermatitis. PMID- 7868776 TI - Is vitiligo a result of migration of melanocytes due to bad local environment? PMID- 7868778 TI - The 128th meeting of the Acoustical Society of America. Austin, Texas, 28 November-2 December 1994. Abstracts. PMID- 7868777 TI - Inguinal hernia in recessive X-linked ichthyosis. PMID- 7868779 TI - Psychoanalysis and the maltreatment of children. AB - This essay presents some of the ideas derived from 30 years of observing and treating abused children and those who abuse them. Although most of these patients have not been in what could be called classical analysis, psychoanalytic principles have been crucially important in understanding their behavior and psychodynamics. I also believe that the study of their life histories can often enhance and sometimes broaden many of our psychoanalytic concepts, especially of ego and superego development and expression. PMID- 7868780 TI - Belief and suggestion in the recovery of memories of childhood sexual abuse. AB - The increasingly frequent clinical reports of the recovery of repressed memories of childhood sexual abuse have drawn both skepticism and support in the analytic community. Two contrasting paradigms are offered to account for the processes by which fully repressed memories are recovered. On the one hand, the analyst's belief that one can reconstruct early traumatic experience creates fertile ground for overt and covert suggestion, which, in conjunction with an anxious patient seeking affiliation, may lead to the production of false memories. On the other hand, the analyst's belief in the likelihood of repressed abuse and that it can be reconstructed may constitute a necessary precondition for the emergence of valid memories. With these beliefs providing an essential holding environment, the recovery of repressed memories of sexual trauma may be an instance of the retrieval of state-dependent memory. Although the preponderance of evidence favors the suggestion hypothesis, the evidence is not conclusive. Which paradigm the analyst adopts, however, carries enormous clinical implications. PMID- 7868781 TI - Establishing trauma: the difficulty distinguishing between memories and fantasies. AB - This paper is intended as a contribution to understanding why, up until recently, there have been so few case reports of actual abuse and its sequelae in the psychoanalytic literature. We suggest that psychoanalytic insights into the nature of psychic reality, while indispensable to the evolution of psychoanalytic thinking, have nonetheless had the adverse effect of collapsing any distinction between unconscious fantasies and repressed memories. Moreover, the idea that knowledge of external reality is itself mentally constructed also has diminished interest in uncovering trauma and "real" history. We present a report of an adult analysis that illustrates the recovery of a dissociated memory of sexual abuse that occurred during adolescence, as a springboard to discuss problems analysts have had in dealing with trauma theoretically. We hypothesize that repressed memories and conscious fantasies can often be distinguished insofar as they may be "stored" or encoded differently, and that consequently the sequelae of trauma and fantasy often, but not always, can be disentangled. We describe some different modes of encoding trauma and some different ways of remembering, reexperiencing, and reenacting it. And, finally, we suggest why traumatic memories are increasingly accessible to patients today. PMID- 7868782 TI - Sexual excitement and countertransference love in the analyst. AB - The psychoanalytic literature has been remarkably silent on the subject of erotic countertransference feelings. The recent emphasis on transference countertransference enactments in the analytic setting has resulted in increased openness about development of such feelings. Several key themes appear to be involved in the analyst's sexual excitement, including loss of the "as-if" nature of transference and countertransference, a measure of hostility and contempt, the perception of a deficit state in the patient, a defense against loss and mourning, and oedipal and preoedipal enactments involving a variety of gender configurations. These themes are illustrated with clinical material. The differences between those analysts who contain and constructively process erotic countertransference and those who destructively act it out are also discussed. The crucial role of consultation with a colleague is emphasized as a valuable recourse. PMID- 7868783 TI - Barriers to love between patient and analyst. AB - Analysts tend to avoid the full range and force of love and hate in themselves and in their analysands. Such affective constriction in the analyst interferes with full analysis of patients' defenses against passionate feelings, loving and hating. I contend that our analytic ego ideal tends to encourage constriction and discomfort with our loving feelings for analysands. My intention is not to advise analysts to love their patients, but to focus carefully on mutually constructed barriers that serve to prevent loving feelings in the analytic setting. I describe some of my loving feelings toward two analysands and some of the obstacles with which I had to struggle in order to preserve such feelings for the sake of these patients' analytic growth and change. PMID- 7868784 TI - Love in the analytic setting. AB - In the context of viewing the analytic setting as a "clinical laboratory" to study the nature of love relations, this paper starts by outlining the relationships of transference love, "normal" love, neurotic love, and oedipal love. After a description of the vicissitudes of transference love when patient and analyst are of the same sex and of opposite sex, developments of transference love regarding homosexual and heterosexual longings in neurotic and narcissistic pathology are considered. Countertransference reactions in response to transference love are explored next, with emphasis on conditions under which erotic countertransference may become particularly intense. In describing the technical management of erotic countertransference, the analyst's ability to explore his own feelings and fantasies without constraint is stressed. The usefulness of understanding the erotic countertransference in arriving at transference interpretations is illustrated by a clinical case of a female patient with a neurotic personality structure and predominantly masochistic conflicts. PMID- 7868785 TI - Addictive sexual behavior. AB - Case material is presented from two patients suffering from addictive sexual behavior. The term addiction is used because of the intense, driven quality of the behavior and because of its mood-elevating effects. Psychodynamically, the patients' sexual acts helped to undo feelings of rejection at the hands of their mothers and to enhance feelings of lovability and of self-esteem. The behavior also helped to neutralize powerful feelings of rage toward the mother. In one patient, the acts also helped to ease inner turmoil related to an underlying attention deficit disorder. I speculate that some adults with addictive sexual behavior may have underlying attention deficit disorders. In both my patients, the sexual behaviors served the self-regulatory function of alleviating inner feelings of anhedonia and depression. When they decreased their sexual activities during the course of the treatment, they required adjunctive antidepressant medication. The underlying meaning of the medication and countertransference attitudes toward such patients are explored. PMID- 7868786 TI - Attitudes and experiences of psychoanalysts in analyzing homosexual patients. AB - In response to a survey, 285 psychoanalysts reported having analyzed 1215 homosexual patients, resulting in 23 percent changing to heterosexuality and 84 percent receiving significant therapeutic benefit. Various statistics and individual comments are reported. Virtually all of the respondents rejected the idea that a homosexual patient in analysis "can and should" change to heterosexuality, although 17 percent had changed their opinion during the last 10 years. Over a third believed that most other psychoanalysts hold this opinion even though they themselves do not. The contention of some gay activists that "traditionally trained" psychoanalysts harm and "abuse" their patients is examined and rejected. PMID- 7868787 TI - What are the boundaries of psychoanalytic work? Panel report. PMID- 7868788 TI - Impasses in psychoanalysis. Panel report. PMID- 7868789 TI - Self-observation, self-analysis, and reanalysis. Panel report. PMID- 7868790 TI - Analyzing the "unanalyzable" patient: implications for technique. Panel report. PMID- 7868792 TI - Concomitant use of psychoanalysis and sexual therapy techniques. PMID- 7868791 TI - Incest and psychoanalysis: are we ready to fully acknowledge, bear, and understand? Panel report. PMID- 7868793 TI - The perpetuation of an error. PMID- 7868794 TI - The fallibility of interpretations. PMID- 7868795 TI - Comment on "Monitoring the analytic surface". PMID- 7868796 TI - Incest, erotic countertransference, and analyst-analysand boundary violations. PMID- 7868797 TI - The uses and abuses of memory. PMID- 7868798 TI - Children, bad happenings, and meanings. PMID- 7868799 TI - A prospective study of hypothalamus pituitary function after cranial irradiation with or without radiosensitizing chemotherapy. AB - Hypopituitarism can occur after cranial irradiation. Combined chemotherapy (CT) and radiotherapy (RT) have greatly improved the survival of patients with nasopharyngeal carcinoma (NPC). We studied 37 NPC patients who received RT and/or CT prospectively to determine if combined CT worsens the radiation damage. Patients were studied before, 6 months, 1 year and 2 years after treatment, with 4 combined hypothalamic releasing hormones stimulation test and insulin hypoglycemic test. Five developed hypothyroidism and 3 developed hyperprolactinemia after treatment. The TSH response to TRH progressively increased. In male patients who received RT only, the LH response to GnRH was reduced after RT. The FSH response to GnRH increased 6 months and 1 year after RT, and returned to pretreatment level 2 years after RT. In male patients who received RT and CT, after an initial rise 6 months after treatment, both FSH and LH responses to GnRH declined. The ACTH response to ovine CRH was decreased 6 months after RT and remained so later on, while the cortisol response became prolonged and enhanced progressively after RT. The peak GH response to GRH increased significantly 1 year after RT in patients who also received CT. The GH response to insulin hypoglycemia was also increased after RT while the cortisol response remained the same. In conclusion, cranial irradiation caused a progressive impairment of the hypothalamus-pituitary-endocrine axes. Combined CT may mask the radiation damage to GnRH neuron by inducing primary hypogonadism. There may be hippocampal damage in addition to hypothalamo-pituitary damage after cranial irradiation. PMID- 7868800 TI - Comparison of immuno- and HPLC-assays for the measurement of urinary collagen cross-links. AB - Pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) are two cross-links of collagen molecules, that are present in the extracellular matrix and released during its degradation. Pyr is present in bone and cartilage, but not in significant amounts in other connective tissues and D-Pyr appears to be specific for bone tissue. Therefore, the urinary excretion of Pyr and D-Pyr might be a sensitive marker of bone matrix degradation. For the determination of urinary Pyr and D-Pyr two methods are available: a chromatographic method (HPLC) by which it is possible to measure separately Pyr and D-Pyr, and a new immunoassay which measures total free and low molecular weight pyridinoline released in the urine. We compared the results obtained by HPLC analysis of 205 urinary samples from normal subjects and patients affected by various bone disorders with those obtained by the immunoassay. The overall correlation coefficient between the results obtained by the two methods was 0.34. When calculated in a range of pyridinoline concentrations from 0 to 30, 30 to 60, and over 60 pmol/mumol creatinine the correlation coefficient was respectively -0.094, 0.38, and 0.12. The two methods yielded variable profiles in the detection of circadian rhythms and these differences did not segregate with normal or pathological conditions. We conclude that the immunoassay proposed for the determination of urinary collagen cross links is not immediately applicable to clinical use. The improvement of the antibody specificity will probably contribute to replace the HPLC method with the immunoassay. PMID- 7868801 TI - Transient central hypothyroidism as a cause of failure to thrive in newborns and infants. AB - The course of two neonates and one 4-month-old infant with laboratory and clinical evidence of central hypothyroidism is described. All three presented with failure to thrive and improved after L-T4 therapy. Early recognition and treatment of newborns and infants with central hypothyroidism is important to maximize the potential for growth and development. Two of the three infants have been documented to have transient central hypothyroidism of hypothalamic origin, not previously reported. PMID- 7868802 TI - Immunological pattern in patients with 21-hydroxylase deficiency. AB - The aim of this work was to perform an immunological study in six patients with 21 hydroxylase deficiency in mild form (M210HD) and in 2 patients with 21 hydroxylase deficiency in classical form (C210HD) and in their parents, in whom a previous HLA,C4,Bf typing demonstrated high prevalence of DR5 and phenotypic absence of fraction C4B of complement (C4BQO). This study contains the evaluation of C3, IgA, IgG, IgM levels, anticardiolipin antibodies (IgG and IgM) and circulating immunocomplexes. A study of lymphocyte subsets was also performed. Among M210HD 1 patient showed presence of anticardiolipin antibodies both IgM and IgG; this patient had shown antinuclear antibodies in a previous study. Among parents, some subjects showed presence of anticardiolipin antibodies and high levels of circulating immunocomplexes. No alterations in C3 and Ig levels were observed. A reduced percentage of CD4 suppressor-inducer (CD4-SI) (p < 0.05 in M210HD and in parents vs controls) and increased percentage of CD4 helper-inducer (CD4-HI) (p < 0.05 in both groups vs controls) were found. No alterations were evidenced in C210HD patients. Data about association between 21-hydroxylase deficiency and autoimmune diseases are rare. Our results confirm that 210HD could be associated to an unbalancement of immune system function and suggest that non immune genes, like 21-hydroxylase one, may influence the expression of autoimmune diseases at least in presence of peculial extended haplotypes. PMID- 7868803 TI - Subclinical hypothyroidism resulting from autoimmune thyroiditis in female patients with endogenous depression. AB - Thyroid function and presence of thyroid autoantibodies were assessed in a group of 75 consecutive female patients with mood disturbances and in a group of 38 healthy women of similar age recruited as controls. Nine patients suffered from major (endogenous) depression and 66 from minor (neurotic) depression. The individual patients had normal values of circulating thyroid hormones. Nevertheless, endogenously depressed patients had total serum triiodothyronine (M +/- SE = 1.49 +/- 0.09 nmol/l) and both total (83.9 +/- 4.3 nmol/l) and free serum thyroxine (13.9 +/- 1.1 pmol/l) lower than in the group of minor depressed and in the group of controls (p < 0.01, in both comparison). The median value of serum thyrotropin was 5.22 mU/l in the major depressed patients versus 1.72 mU/l in the minor depressed and 1.69 mU/l in the controls. Thyroid function test results in the minor depressed group did not significantly differ from those in the controls. Five of the 9 endogenously depressed patients were subclinically hypothyroid, while none of the 66 patients with minor depressive disorder showed thyroid dysfunction. Antibodies against thyroglobulin and/or thyroid peroxidase were positive in all the 5 endogenously depressed women with subclinical hypothyroidism, revealing a symptomless autoimmune thyroiditis, which was also confirmed by ultrasonography in all cases and histopathologically demonstrated in one case. None of the endogenously depressed women without thyroid dysfunction and none of the 66 minor depressives were seropositive for thyroid autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868804 TI - Reduction of endogenous, ovarian and adrenal androgens with ketoconazole does not alter insulin response in the polycystic ovary syndrome. AB - Several different strategies were used to investigate the relationship between hyperandrogenism and hyperinsulinemia associated with polycystic ovary syndrome. Ketoconazole was given orally (400 mg/day) for 9 months to evaluate the effect of reduction in ovarian and adrenal androgens on insulin response (oral glucose tolerance test) in 35 women with polycystic ovary syndrome. Androgenic steroids (testosterone, androstenedione, dehydroepiandrosterone sulphate, and free testosterone index) decreased (p < 0.01), but basal insulinemia, maximum peak insulin, and insulin/glucose ratio showed no significant changes. One month after treatment was stopped, free testosterone index, and serum concentrations of androstenedione and testosterone, increased (p < 0.05), but no alterations were noted in insulin parameters. Body mass index was stable throughout the ten-month study period. Our findings suggest that endogenous androgens, no matter whether they are of ovarian or adrenal origin, do not play a major role in the modulation of hyperinsulinemia in patients with polycystic ovary syndrome. PMID- 7868805 TI - Endemic goiter and thyroid function in central-southern Sardinia. Report on an extensive epidemiological survey. AB - Although the existence of endemic goiter and cretinism in Sardinia is known since to ancient time, scanty information collected according to WHO criteria is available. In the present paper the results of an extensive epidemiological survey carried out in juvenile population living in some rural and/or hilly villages in the provinces of Nuoro and Oristano in Central-Southern Sardinia and in urban area of Cagliari, are reported. In the majority of the villages the mean urinary iodine excretion was lower than 60 micrograms/L; the goiter prevalence ranged between 39% and 61% in the district of Nuoro and between 21% and 56% in the district of Oristano. In the control area the urinary iodine excretion was 105 micrograms/L with a goiter prevalence of 12%. Goiter prevalence was not always inversely related to urinary iodine excretion. No relevant thyroid function alterations were found. IN CONCLUSION: 1) in extraurban areas of Central Southern Sardinia mild to moderate iodine deficiency and endemic goiter are still a widespread problems; 2) also in urban area endemic goiter prevalence is still higher than 10%; 3) extemporary urinary samples are inadequate for assessing the severity of goiter endemia in mild to moderate iodine deficiency; 4) in mildly affected districts palpation is inaccurate for assessing the prevalence of goiter; 5) no relevant alterations of thyroid function were documented in juvenile population. PMID- 7868806 TI - Acquired nephrogenic diabetes insipidus secondary to distal renal tubular acidosis and nephrocalcinosis associated with Sjogren's syndrome. AB - A 52-year-old woman was referred to our hospital because of 16-year history of polyuria and polydipsia. Hyposthenuria, hyperchloremic metabolic acidosis and the inabilities to acidify the urine after acid-loading test and to concentrate the urine in responses to water-deprivation and antidiuretic hormone administration allowed us to diagnose renal tubular acidosis and nephrogenic diabetes insipidus. Radiographic examinations revealed bilateral nephrocalcinosis. The patient was also found to have clinical and laboratory findings characteristic for Sjogren's syndrome. Thus the longstanding, poorly monitored distal renal tubular acidosis associated with Sjogren's syndrome was considered to result in very rare renal complications-nephrocalcinosis and nephrogenic diabetes insipidus. In patients with renal tubular acidosis and/or nephrogenic diabetes insipidus of unknown etiology, therefore, Sjogren's syndrome should be considered as one of primary disorders. PMID- 7868807 TI - Adrenal insufficiency in a man with non-classical 21-hydroxylase deficiency: consequence or coincidence? AB - Deficiency of the adrenal enzyme 21-hydroxylase, which is required for cortisol synthesis, appears in two forms: a rare classical variant with severe enzyme deficiency, usually presenting in neonates with ambiguous genitalia (from androgen overproduction) or adrenal crisis (from glucocorticoid and mineralocorticoid underproduction), and a common (1% of the general population) non-classical variant with mild enzyme deficiency, usually presenting in young adults with findings of androgen excess but without clinical evidence of decreased steroid hormone production. We describe a 22-year-old man who had clinical and biochemical findings consistent with adrenal insufficiency, including a favorable response to hydrocortisone replacement, in whom elevated serum levels of the cortisol precursor 17-hydroxyprogesterone were diagnostic of non-classical 21-hydroxylase deficiency and in whom no other cause of adrenal insufficiency could be identified. These findings raise the possibility that non classical 21-hydroxylase deficiency, an extremely frequent disorder which is generally thought to be without significant morbidity, might cause or contribute to adrenal insufficiency in adults. PMID- 7868808 TI - IgA anti-eye muscle cytosol autoantibodies and the clinical stage in Graves' disease. PMID- 7868809 TI - Flutamide and hirsutism. PMID- 7868810 TI - Levothyroxine suppressive therapy: harmful and useless or harmless and useful? PMID- 7868812 TI - Lack of stimulatory effect of 1,25(OH)2 vitamin D3 on beta-endorphin and cortisol secretion. AB - The aim of the work was to investigate the effect of 1,25 (OH)2 vitamin D3 on beta-endorphin and cortisol secretion in vivo. beta-Endorphin, cortisol, calcium and phosphate in blood were measured in ten healthy unstressed volunteers before and after 4-day oral administration of 1,25 (OH)2 vitamin D3 in doses of 3 micrograms/d. The biological effectiveness of the treatment was proved by a significant increase of calcemia as compared with control values (2.71 +/- 0.03 vs 2.57 +/- 0.02 mmol/l, mean +/- SE, p < 0.01) and phosphatemia (1.18 +/- 0.06 vs 0.89 +/- 0.01 mmol/l, p < 0.01). beta-Endorphin after treatment was 39.1 +/- 9.2 (vs 42.7 +/- 7.6) ng/l and cortisol 369 +/- 35 (vs 377 +/- 31) nmol/l. In conclusion, in spite of the good compliance of the treatment, 1,25 (OH)2-vitamin D3 stimulates neither beta-endorphin nor cortisol secretion in healthy subjects. PMID- 7868811 TI - Uteroglobin and uteroglobin-like proteins: the uteroglobin family of proteins. PMID- 7868813 TI - Ontogeny of the circadian rhythm in medial basal hypothalamic beta-endorphin content in female rat. AB - The present study evaluated the possible role of estrogens in generating the circadian rhythm of medial basal hypothalamus content at the time of puberty in female rats. Accordingly, changes in medial basal hypothalamus beta-endorphin (beta-EP) content were investigated in female rats, before and at puberty. Groups of intact or ovariectomized rats were studied after estradiol-benzoate or placebo treatment. The results showed that circadian rhythm of beta-EP content of medial basal hypothalamus is absent in prepubertal rats, while it appears at puberty, associated to a significant increase of beta-EP concentration. The primary involvement of steroids in generating this circadian rhythm was supported by the finding that estradiol-benzoate treatment caused a precocious appearance of beta EP hypothalamic diurnal changes in prepubertal rats. Moreover, estradiol-benzoate replacement restored the loss of beta-EP nocturnal increase induced by ovariectomy in pubertal animals. Therefore, these data support the significant role of estrogen in inducing the circadian rhythm of beta-EP content in medial basal hypothalamus at the time of puberty in female rats. PMID- 7868814 TI - Recovery of visual and endocrine function following transsphenoidal surgery of large nonfunctioning pituitary adenomas. AB - A series of 35 patients with non-functioning pituitary adenomas undergoing transsphenoidal surgery is presented. In most cases, the presenting symptoms were related to the mass effect of the tumor. There was no operative mortality. Before surgery, visual field defects were documented in 21 patients (60%). After surgery, excluding 3 patients with preoperative blindness, 28% regained normal vision and 67% showed variable improvement. Preoperatively, 24 patients (69%) had abnormal pituitary function, 24 (69%) had hypogonadism, 7 (20%) adrenal insufficiency, 8 (23%) hypothyroidism and 2 (6%) panhypopituitarism. After pituitary surgery, all but one patient with normal preoperative function retained it. Of the patients with hypopituitarism, 11 (46%) had variable improvement and 13 (54%) had persistent deficits. After surgery, 4 patients (57%) with adrenal insufficiency recovered normal adrenal function, 7 patients (29%) with hypogonadism recovered gonadal function and 1 patient (13%) with hypothyroidism recovered thyroid function. Prior to surgery, the presence of a normal or slightly elevated PRL and a rise in TSH after TRH and in LH after GnRH stimulation were of value in predicting possible recovery of pituitary function after surgery. These observations suggest the presence of viable pituitary tissue in these cases and point out that, in some instances, the mechanism of hypopituitarism may be compression of the portal circulation, rather than destruction of the normal pituitary gland. PMID- 7868815 TI - Decreased expression of insulin-sensitive glucose transporter mRNA (GLUT-4) in adipose tissue of non-insulin-dependent diabetic and obese patients: evaluation by a simplified quantitative PCR assay. AB - Impaired cellular uptake and utilization of glucose is the hallmark of non insulin-dependent-diabetes (NIDDM). We have developed a quantitative assay to probe the expression of glucose-transporter genes in tissues derived from patients with NIDDM. Using the polymerase chain reaction (PCR), we assessed levels of expression of the insulin responsive glucose transporter GLUT-4 in adipose tissue of patients with NIDDM and in obese patients. We report that expression of GLUT-4 is reduced in NIDDM and in obesity associated with hyperinsulinemia and insulin resistance. These results suggest that reduction of GLUT-4 levels in the adipose cell plays an important role in the pathogenesis of insulin resistance, an early feature of NIDDM. PMID- 7868816 TI - Relationship between hypophyseal portal GHRH and somatostatin and peripheral GH levels in the conscious sheep. AB - The mechanisms involved in the genesis of pulsatile GH secretion are not well understood. Recently, methods for hypophyseal portal blood collection in conscious sheep became available. Using this method, GHRH and SRIH secretion into hypophyseal portal blood (HPB) and GH release from the pituitary gland were simultaneous assessed and the relationship between GHRH and SRIH changes in HPB and GH in peripheral blood was investigated. In 23 rams (9-11 month old, 35-45 kg bw), 126 hours of HPB were analysed. Fifty-four spontaneous GH peaks were detected. The majority of GH peaks (48.1%) was associated with an increased portal GHRH and a fall in somatostatin concentrations. A simultaneous increase in GHRH and somatostatin levels was observed in 18.5% of GH peaks while 12.9% of peaks occurred with a fall in SRIH and no modification in GHRH concentrations. Finally, 5/54 (9.3%) GH peaks occurred without any modification in portal GHRH and SRIH release. Our data indicate that the GHRH/SRIH interplay is complex. The occurrence of spontaneous GH peaks may be due not only to a coordinate increase in GHRH and reduction in SRIH release similar to male rat, but also to other patterns of GHRH/SRIH secretion. PMID- 7868817 TI - Direct action of LH RH and its antagonist on isolated bovine granulosa cells steroidogenesis. AB - Progesterone, 4-androstene-3,17-dione, testosterone and estradiol-17 beta secretion by bovine granulosa cells culture without or in the presence of 10, 100 or 10.000 ng/ml LH RH or of its antagonist (D Phe2, D Phe6) LH RH were analyzed. It was observed that both LH RH and its antagonist significantly activated progesterone and estradiol output. LH RH also stimulated, but (D Phe2, D Phe6) LH RH inhibited granulosa 4-androstene-3,17-dione secretion. Both LH RH and its analogue decreased testosterone release by the cell culture. This is the first demonstration of a direct influence of LH RH on bovine ovarian steroidogenesis. The lack of correlation between LH RH and its agonist action on hypophysis and on different gonadal steroids secretion may suggest the differences in the features of receptors to LH RH-related peptides in the various target cells. PMID- 7868818 TI - Inter and intra-individual variability of sperm morphology after selection with three different techniques: layering, swimup from pellet and percoll. AB - Sperm morphology has been suggested to be one of the most reliable factor in predicting male fertility potential both in spontaneous cycles and in assisted reproduction. In this work the morphology of spermatozoa selected with three different techniques (layering, swimup from pellet and mini-percoll) has been assessed and compared in 20 infertile patients. All the techniques allowed the recovery of sperm populations of a better quality than in basal samples, with a higher percentage of normal forms (p < 0.001). No significant differences were observed among the three different techniques in selecting sperm populations. The scatter diagrams comparing pairwise differences between the methods against their means regard the percentage of normal forms selected show a great (over 20%) inter and intra-individual variability. These data demonstrate that the three techniques select different percentages of normal spermatozoa, even in the same patient. Since it is crucial to obtain the highest number of morphologically normal and motile spermatozoa and each technique may provide different results in a given patient, we suggest that at least two techniques of sperm selection be performed before assisted reproduction procedures. This combined testing could also be relevant in the prognostic evaluation of the infertile male, since it explores the different characteristics of sperm function. PMID- 7868819 TI - Riedel's thyroiditis associated with high titers of antimicrosomal and antithyroglobulin antibodies and hypothyroidism. AB - Riedel's thyroiditis is a rare, chronic inflammatory disease of the thyroid gland. The aggressive fibrosis with extension beyond the thyroid into adjacent tissues contrasts with the diffuse, but intracapsular fibrosis of Hashimoto's thyroiditis. Most current studies refute the possibility of progression from a highly fibrosing form of Hashimoto's thyroiditis to a Riedel's thyroiditis based on the distinct clinical and laboratory data, although an unknown immunological basis is suggested for both diseases. The authors describe a patient with Riedel's thyroiditis, probably associated with Hashimoto's thyroiditis, sent to surgery because her cytological examination suggested thyroid malignancy. This patient had clinical and laboratory features of hypothyroidism and very high titers of antimicrosomal and antithyroglobulin antibodies, which decreased after surgery. Pathology studies disclosed Riedel's thyroiditis with intense lymphocytic infiltration suggestive of Hashimoto's thyroiditis. Quantitative immunohistochemical studies were not able to distinguish between both diseases. PMID- 7868822 TI - Oxidative stress in childhood malnutrition and diarrhoeal diseases. PMID- 7868823 TI - Diarrhoea and mortality in Menoufia, Egypt. AB - From 1982 the Ministry of Health of Egypt implemented the National Control of Diarrhoeal Diseases Project (NCDDP) which attempted to improve case management of childhood diarrhoea by making oral rehydration salts (ORS) widely available and used, to improve feeding patterns during diarrhoea, and other measures. National data indicate a high level of success in achieving the targets. However, impact evaluation is hampered by weak national baseline information available prior to NCDDP on case management of diarrhoea and causes of infant and childhood mortality. A study in Menoufia Governorate in 1979-80 obtained such information. Consequently, in 1988 the area was revisited to examine subsequent changes. Findings showed marked improvement in case management of diarrhoea and rapid mortality decline, with diarrhoeal mortality apparently declining somewhat faster than mortality from other causes. PMID- 7868824 TI - Multidrug resistant Shigella infections in children. PMID- 7868821 TI - Hormonal and local regulation of uterine activity during parturition: Part II- The prostaglandin and adrenergic systems. PMID- 7868820 TI - Hormonal and local regulation of uterine activity during parturition: Part I--The oxytocin system. PMID- 7868825 TI - Levels, trends and causes of mortality in children below 5 years of age in Bangladesh: findings from a national survey. AB - A nationwide survey, conducted in 1992-93 by the Control of Diarrhoeal Disease Programme, Government of Bangladesh, made national estimates of levels and causes of child mortality. A gradual downward trend in infant and child mortality was observed from the mid 1980s. Current mortality rates among infants and children below 5 years were estimated to be around 100 and 150 per 1,000 live births respectively. More than a quarter of deaths in children below 5 years were found to be associated with diarrhoea. Acute respiratory tract infections were also shown to be a major killer of young children. PMID- 7868826 TI - Coproantibodies to rotavirus serotype 1 infection in German children. AB - One hundred and ninety-eight serial stool samples were collected from 27 infants and children hospitalized in Bochum, Germany with gastroenteritis due to serotype 1 rotavirus (RV). RV antigen and RV-specific antibodies (Ab) (IgA ELISA and RV Wa neutralizing Ab) were measured. The prevalence of RV-Ab positive stool samples in RV patients did not differ from that in stool samples from 80 control patients (40% and 42% for ELISA Ab and 11% and 6% for neutralizing Ab, respectively). None of the patients was breastfed in the week preceding stool collection. No significant increase in the prevalence of RV-Ab was observed between stool samples obtained during the early and late phase of hospitalization. We observed patients that continued to excrete RV antigen in the presence of neutralizing stool activities, and patients that showed cessation of RV stool excretion and resolution of clinical symptoms in the absence of RV-neutralizing activity in the stool samples. PMID- 7868827 TI - Clostridium perfringens type A enterotoxin induces tissue damage and fluid accumulation in rabbit ileum. AB - Rabbit ileal loops were treated with purified Clostridium perfringens enterotoxin (CPE) to compare the onset of toxin-induced tissue damage with the onset of fluid transport changes (i.e. diarrhoea). Mild changes in fluid transport were detectable after 15 minutes of toxin treatment and then increased progressively with time. Histopathologic studies on toxin-treated ileal loops and measurement of toxin-treated loop fluid protein contents (an indirect marker for tissue damage) both indicated that detectable CPE-induced tissue damage also occurred within 15 minutes of toxin treatment and then progressively increased for at least the first 30 minutes of CPE treatment. Luminal fluid from CPE-treated loops contained elevated Ca2+ levels compared to control luminal fluid, but these elevated Ca2+ levels were not required to initiate in vivo CPE pathophysiologic effects. Since the onsets and severity of tissue damage and fluid transport changes coincided for at least the first 30 minutes of CPE treatment in our study, these results are consistent with CPE-induced tissue damage having a role in the initiation and extent of diarrhoea occurring during C. perfringens type A food poisoning. PMID- 7868828 TI - Indicators for antibiotic therapy in invasive bacteria diarrhoea. AB - The objective of the study was to determine the clinical indications for antibiotic therapy in diarrhoeal diseases (DD) in 619 children aged 6 to 59 months who were evaluated during a clinical study of diarrhoea. The patients were seen at the outpatient clinic of the Palembang General Hospital from May 1991 through March 1992. Data concerning abdominal pain, pain during defecation, fever, status of breastfeeding, vomiting, mucoid stool, bloody stool, abdominal distention, stool leucocytes and erythrocytes were analyzed to determine their predictive value (PPV) in relation to the bacterial isolation of pathogen in the stool. All clinical variables examined had a low PPV for isolation of any enteric pathogen, including Shigella. The PPV of grossly bloody diarrhoea was 20.8% (95% confidence limits 17.6%-24%), and that of body temperature (> 37.5 degrees C) was 19.6%. When the stool leucocytes were 10 or more per high-power microscopic field (HPMF), the PPV was 22.2%; of erythrocytes found microscopically in the stool, 19.6%. We recommend that those patients with bloody stools and mucoid stools with temperatures of 37.5 degrees C get antibiotics (22%). Second, those patients having 10 or more leucocytes per HPMF plus those with red cells in stools (regardless of the number) should receive either antibiotics and or amoebicides if amoebae are present (5%). PMID- 7868829 TI - Severity of cholera during concurrent infections with other enteric pathogens. AB - In a clinic-based case-control study in Bangladesh we evaluated whether children with diarrhoea due to V. cholerae O1 in association with other enteric pathogen(s) are likely to manifest more severe disease as indicated by development of moderate or severe dehydration. Children with moderate or severe dehydration were defined as cases and those with no dehydration were controls; both cases and controls had acute diarrhoea. A systematic sample of 268 dehydrated cases and 699 nondehydrated controls aged 1-35 months with acute watery diarrhoea of 6 days or less was included. In a multivariate analysis it has been shown that infection with Vibrio cholerae O1 in association with another diarrhoea pathogen (odds ratio = 7.07) was strongly correlated with status of dehydration than those with the V. cholerae O1 infection as a single pathogen (odds ratio = 3.63). Either group was associated with significant risk of dehydration. The results of the study suggest that more than one enteropathogen may be simultaneously involved in causing severe diarrhoea, and appropriate public health measures to reduce environmental contamination should be beneficia PMID- 7868830 TI - Intrafamilial outbreak of astrovirus gastroenteritis in Sao Paulo, Brazil. AB - This report describes an intrafamilial outbreak of astrovirus-associated gastroenteritis that occurred among 5 children in a family living in the State of Sao Paul, Brazil. Astrovirus was detected by direct electron microscopy (DEM) and confirmed by solid phase immune electron microscopy (SPIEM) using astrovirus reference serum (T2-6-89). The rise in titre of astrovirus antibody in patients' sera was observed by IEM using acute and convalescent-phase sera. Combined use of the EM techniques to detect virus in stool and antibody rise in sera led us to conclude that this intrafamilial outbreak might have been caused by astrovirus infection. In Brazil, astrovirus may be a more common agent of gastroenteritis than in currently appreciated. PMID- 7868831 TI - Distribution of Zonula occludens toxin (zot) gene among clinical isolates of Vibrio cholerae O1 from Bangladesh and Africa. AB - Seventy-two clinical isolates of Vibrio cholerae O1 from Bangladesh, and 12 and 9 isolates respectively from Tanzania and Nigeria were screened for sequences homologous to zonula occludens toxin (zot) and cholera toxin (ctx) genes. As observed previously, all isolates in the present study also possessed sequences for both toxins which suggested that zot does not occur independent of ctx. It appears that along with the virulence genes located in the "virulence cassette" region of the bacterial chromosome, zot may play a role in the pathogenesis of cholera. PMID- 7868832 TI - Intestinal perforation in a child with Shigella dysenteriae type 1 infection: a rare complication. PMID- 7868833 TI - Bibliography on diarrhoeal diseases. PMID- 7868834 TI - HIV antibodies among intravenous drug users in Bahrain. AB - A 12-month study was conducted to identify risk factors for human immunodeficiency virus (HIV) infections among intravenous drug users (IDU) attending drug rehabilitation clinic of the Psychiatric Hospital, Manama, Bahrain. Patients provided demographic and behavioural information based on a questionnaire. Two hundred and forty male IDUs participated in the study on voluntary basis. The seroprevalence of HIV was 21.1 per cent. The presence of HIV antibody was associated with educational status, frequency of injecting drugs and needle sharing. PMID- 7868835 TI - Host feeding patterns of Culex vishnui sub group of mosquitoes in Dibrugarh district of Assam. AB - The host feeding patterns of three species of mosquitoes belonging to vishnui sub group, Culex tritaeniorhynchus, Culex vishnui and Culex pseudovishnui, the most prevalent species in Dibrugarh district were determined by analysing their blood meals. All 3 species were found be essentially zoophilic. High percentage of pig feeding was observed in Culex tritaeniorhynchus (40 per cent) and Culex vishnui (35.3 per cent) in comparison to other prevalent species in this area. In contrast Culex pseudovishnui another member of this group was not attracted to pigs (0.4 per cent). Few human feeds were recorded for Culex tritaeniorhynchus (0.4 per cent), Culex vishnui (0.4 per cent) and Culex pseudovishnui (0.8 per cent), indicating their occasional contact with human hosts. Considering the importance of this group as proven vectors of Japanese encephalitis the relevance of these results to JE transmission in this area are discussed. PMID- 7868836 TI - Clinical evaluation of purified vero-cell rabies vaccine in patients bitten by rabid animals in India. AB - Fifty-five individuals bitten by rabid animals were administered purified vero cell rabies vaccine (PVRV) at WHO Collaborative Centre for Rabies Epidemiology for South-East Asia at National Institute of Communicable Diseases, Delhi to test its immunogenicity, inocuity, safety and clinical efficacy. Fifty-two (94.5 per cent) of these individuals underwent complete course of treatment. Sera samples collected prior to the commencement of treatment showed all these persons to be sero-negative for antibody against Rabies virus. However mean titre of 2.44 I.U./ml, 7.76 I.U./ml and 10.77 I.U./ml were detected after third, fourth and sixth injections, respectively of PVRV. Persistance of protective titres of this antibody could be demonstrated even after 15 months of treatment. Of 327 inoculations, local and general reactions were observed after 10.6 per cent inoculations. All these cases were followed up for periods between 7 and 25 months and were, alive and healthy till the end of observation period, thereby proving the efficacy of the vaccine in preventing rabies. PMID- 7868837 TI - Antibacterial activity of tea (Camellia sinensis) and coffee (Coffee arabica) with special reference to Salmonella typhimurium. AB - Extracts of Black tea, Japanese green tea, China tea or Coffee inhibited the growth of various bacteria causing diarrhoeal diseases. Tea or coffee also showed bactericidal activity against Vibrio cholerae, Salmonella typhimurium and Salmonella typhi. PMID- 7868838 TI - Field evaluation of trivalent oral polio vaccine efficacy in Madras city--a case control study. AB - Evaluation of Trivalent Polio Oral Vaccine efficacy under field conditions was carried out, in Madras city. Relative risk of provocative paralysis by IM injection was also studied. The study includes 52 cases and 104 age and sex matched control cases. Vaccine Efficacy (VE) was found to be 75 per cent and 95 per cent by matched pair analysis with control Group. I and II respectively and 87 per cent (95 per cent confidence limits between 90 and 97 per cent) by triplet analysis. The relative risk of giving injection during the prodromal stage in provoking paralysis was found to be 18, 10 and 13, by matched and triplet analysis respectively. PMID- 7868839 TI - Comparative repellent properties of certain chemicals against mosquitoes, house flies and cockroaches using modified techniques. AB - Several terpenoids were assessed for their repellent/toxic properties against mosquitoes (Aedes aegypti), house flies (Musca domestica) and cockroaches (Periplaneta americana). Impregnated wide mesh netting was used in the case of the Dipterans, while treated filtered paper was employed for the bioassays with cockroaches. Persistence of the repellent chemicals was studied. Doses ranged from 5-20 gm/M2 for the Dipterans and 25-100 mg per 4 x 4 cm filter paper for the cockroaches. Dimethyl phthalate (DMP) offered the maximum protection of the chemicals tested against mosquitoes but was not so effective against house flies and cockroaches. Citral and Eugenol were effective against all the three test insects. Other test compounds afforded varying degrees of protection. Application strategy and utility of the findings are discussed. PMID- 7868840 TI - Community based survey of STD/HIV infection among commercial sexworkers in Calcutta (India). Part I. Some social features of commercial sexworkers. AB - A community based sample survey of sexually transmitted diseases and Human Immuno deficiency Virus infection was carried out among commercial sex workers of a red light area in Calcutta. In this paper socio-demographic aspects of sex workers are discussed. For the survey, 450 sex workers were selected by random sampling method. Among the sex workers surveyed, 84.89 per cent were in the age group 15 29 years. Lowest age was 13 years and mean age was 23.12 years. Large number of sex workers were from Nepal (15.11 per cent) and Bangladesh (11.78 per cent). About 38 per cent were from three districts of West Bengal bordering Bangladesh. About 84.44 per cent of the sex workers were illiterate. Extreme poverty forced 49.10 per cent to choose this profession and family disturbances led 21.56 per cent to this profession. Almost all sex workers (448) had addiction, alcohol being taken regularly by 81.11 per cent. Number of clients of sex workers varied from 2 to 10, average being 3. About 67.33 per cent gave history of pregnancy, 46 per cent had abortion and 41.11 per cent had living children. About 27.11 per cent took precaution against pregnancy regularly. Use of oral pills was found to be the most common practice against pregnancy (13.65 per cent), followed by ligation (11.56 per cent). Only 1.11 per cent reported that their clients used condom regularly. PMID- 7868841 TI - Community based survey of STD/HIV infection among commercial sex-workers in Calcutta (India). Part II. Sexual behaviour, knowledge and attitude towards STD. AB - A community based sample survey of STD/HIV infections was carried out among 450 commercial sex workers, (CSW) of one red light area in Calcutta. In this paper, sexual practices of sex workers, their knowledge about sexually transmitted diseases (STD) and practice of preventive and curative measures against STDs, is described. Vaginal intercourse was the usual sexual practice. But as many as 74.44 per cent also practised oral sex. About 82.67 per cent had the practice of washing external genitalia with antiseptic solution after sexual intercourse. About 69.11 per cent of sex workers were aware of sexually transmitted diseases and 30.67 per cent had knowledge about AIDS. About 70.22 per cent had symptoms related to genital tract during one year preceding the survey and 34 per cent of sex workers took medical treatment during last one month. PMID- 7868842 TI - A comparative study on the optimum time and method of collection of Phlebotomus argentipes and other sandflies. (Diptera: Psychodidae). AB - A uniform method of collection is imperative for generating comparable entomological data in connection with studies on efficacy of vector control measures against sandflies. Two commonly employed methods for sandfly collections i.e. hand collection by aspirator and sticky paper traps were compared under similar ecological conditions to determine the optimum time and method for generating data on relevant indices. Only two P. argentipes male specimens were collected at dusk time from 12 cattle sheds and 40 human dwelling by aspirator method. By sticky traps placed in the same resting shelters, 243 P. argentipes and 58 specimens of 5 other species were collected. However, the collection by sticky traps comprised only males and unfed females. In the morning collection by aspirators 268 sandflies of 8 species in all stages of gonotropic cycle were collected. It is concluded that morning collections by aspirator method can provide objective assessment of control measures. Sticky traps may be useful as additional method for confirming presence of P. argentipes in sprayed areas. PMID- 7868843 TI - Endemicity of multidrug resistant Salmonella infection in rural areas of Ahmednagar district, Maharashtra. PMID- 7868844 TI - Fluvoxamine. A review of its safety profile in world-wide studies. AB - Fluvoxamine, a selective serotonin reuptake inhibitor, was studied extensively in 34,587 predominantly depressed patients in 66 studies conducted world-wide. These studies were largely uncontrolled trials representing the use of fluvoxamine by psychiatric and general practice physicians in everyday conditions. The safety data were analyzed according to standardized medical review and data management policies. Approximately 70% of the fluvoxamine population were female and 44% were aged 31-51 years. The modal total daily dose was 100 mg. Safety findings revealed a pharmacological adverse event profile similar to that seen with other serotonin reuptake inhibitors. Nausea was found to be the only common symptom, with an incidence rate of 16%. Approximately 2% of the fluvoxamine population reported at least one serious adverse event (per FDA criteria). Overall suicidality rates of fluvoxamine were found to be low (0.7%). No cases of zimelidine syndrome, bleeding syndrome or Guillain-Barre syndrome were identified. Overall, fluvoxamine was found to be safe and well tolerated suggesting a favorable alternative in the treatment of depression. PMID- 7868845 TI - Reducing the economic burden of depression. AB - Depressive illness places an enormous economic burden on health services, the community and the individual patient. It is a serious medical disorder associated with high levels of social and physical disability. Antidepressant drug therapy can produce significant improvement in the majority of patients. However, despite its high prevalence depressive illness is frequently undetected, misdiagnosed or inappropriately treated. The selection of a cost-effective antidepressant requires a broad evaluation of the risks, costs and benefits. A choice should not be made on prescription drug costs alone but on the basis of the overall value a treatment option offers in the management of illness. Benefits, such as improved treatment compliance, reduced toxicity in overdose, long-term safety and efficacy in the prevention of relapse and recurrence of depression, improved patient quality of life and decreased accident liability all have cost implications which must be considered when determining the relative cost of medication. PMID- 7868846 TI - How long to onset of antidepressant action: a meta-analysis of patients treated with fluoxetine or placebo. AB - The onset of action of antidepressant medications is commonly believed to require three or more weeks based on clinical observation and corollary receptor-based hypotheses. However, this is not congruent with early published observations with the tricyclic antidepressants and has been recently challenged. Time to response has implications for treatment compliance, dose adjustment, patient well-being, and the associated economic costs of depression. Weekly improvement on the 21 item Hamilton Depression Rating Scale (HAMD21) from baseline and time to response for fluoxetine- and placebo-treated patients were compared. Data from six double blind clinical trials of 6-7 weeks' duration, in which 1447 patients with DSM-III R major depression had been randomly allocated to fluoxetine (n = 962) or placebo (n = 485), were pooled. Analysis of variance was used to evaluate HAMD21 improvement and the Kaplan-Meier estimate was used to evaluate time to response (> or = 50% improvement in HAMD21). Improvement in HAMD21 was statistically significantly greater for fluoxetine than placebo beginning at Week 1 and continuing throughout all weeks of therapy. However, Week 1 and 2 results varied among the individual studies. HAMD factors of cognition and psychomotor status revealed the most rapid changes for fluoxetine-treated compared with placebo treated patients. The probability of achieving a clinical response, defined as a HAMD21 score reduction from baseline of at least 50%, was similar for both fluoxetine (0.043) and placebo (0.049) at the end of Week 1. However, by Week 2 and thereafter the probability of a response was greater for fluoxetine than placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868847 TI - Zopiclone improves sleep quality and daytime well-being in insomniac patients: comparison with triazolam, flunitrazepam and placebo. AB - In a randomized, double-blind, parallel group study in private practice, zopiclone given for 28 days was compared with flunitrazepam, triazolam and placebo in its effect on quality of sleep and daytime well-being in 1507 patients suffering from insomnia. For quantitative assessment, patients were defined as responders according to either a shortening of sleep latency by at least 15 min, or prolongation of total sleep time by at least 20%, or reduction of the number of nocturnal awakenings to three or less and a fresh feeling in the morning, as well as lack of impairment in daytime well-being as a result of tiredness or anxiety. The responder rate tended to be higher with zopiclone (37.4%) than with flunitrazepam (30%) and triazolam (32.2%) and was significantly greater (p = 0.0017) than with placebo (26.8%). Daytime well-being was particularly responsive to zopiclone and most responsive in severe insomniacs. With the exception of those to triazolam, rates of response were most pronounced in patients with insomnia of a short duration (< or = 1 year) than in those with insomnia of a longer duration (> or = 1 year). Following discontinuation of treatment, all groups showed a moderate reduction in therapeutic effect, but no rebound insomnia occurred. PMID- 7868848 TI - Tacrine in Alzheimer's disease: pharmacokinetic and clinical comparison of oral and rectal administration. AB - In a previous pharmacokinetic study in Alzheimer patients great inter-individual variation and low oral bioavailability of the cholinesterase inhibitor tacrine (tetrahydroaminoacridine, THA) were found. In the present investigation oral and rectal administration of tacrine were compared with the aim to find a route for improved bioavailability through diminished first-pass metabolism in the liver. Eight patients suffering from Alzheimer's dementia were given tacrine by oral (25 and 50 mg b.i.d.) and rectal (12.5 and 25 mg b.i.d.) routes for 1 week with 4-6 weeks washout in between. Drug hydroxylation capacity in the patients was determined using the debrisoquine test. Levels of tacrine in plasma and cerebrospinal fluid (CSF) were determined and the cognitive performance was examined by the Mini-Mental State Examination (MMSE) and the Alzheimer Deficit Assessment Scale (ADAS). Tacrine was well tolerated in all but one patient, a slow hydroxylator, who developed an aplastic anemia. MMSE and ADAS scores did not significantly change, except for word recall which was improved on tacrine when given by the rectal route. Pharmacokinetic analysis of the two administration routes revealed that the drug dose may be reduced by almost 50% when given rectally compared to orally. Concentrations of tacrine in the CSF were significantly lower and correlated linearly with the concentrations in plasma. PMID- 7868849 TI - A double-blind, placebo-controlled study comparing mianserin and amitriptyline in moderately depressed outpatients. AB - We report on the results of a study comparing mianserin with amitriptyline and placebo, in outpatients with major depression (DSM-III 296.2 or 296.3). One hundred and forty-nine patients were randomized to mianserin (n = 50), amitriptyline (n = 50) or placebo (n = 49). Medication was taken in a nightly (qhs) dose. During Week 1, the maximum dose was 60 mg mianserin, 120 mg amitriptyline or two placebo capsules. Beginning at Day 7 (through Day 42) maximum dosages were 150 mg mianserin, 300 mg amitriptyline or five placebo capsules. At multiple weeks and endpoint, statistically significant reductions in the Hamilton Depression Scale (HAM-D) 17- and 21-item scores were recorded for both active drugs compared with placebo. Positive results with the HAM-D were corroborated by other measures of efficacy. There were no statistically significant differences between mianserin and amitriptyline in terms of efficacy; however, the results do suggest a more rapid therapeutic response for mianserin compared with amitriptyline, in terms of percentage of patients showing > or = 50% improvement at Weeks 2 (30% vs 23%) and 4 (61% vs 44%). The most common adverse experiences were somnolence (amitriptyline and mianserin 60%, placebo 31%) and dry mouth (amitriptyline 76%, mianserin 30% and placebo 20%). Our results indicate that mianserin is clearly superior to placebo, compares favorably with amitriptyline, and is a safe, well-tolerated, effective medication in the treatment of depressed outpatients. PMID- 7868850 TI - Adjunctive fluoxetine in the treatment of negative symptoms in chronic schizophrenic patients. AB - The effect of adjunctive fluoxetine on negative schizophrenic symptoms was evaluated in 34 chronic schizophrenic in-patients on maintenance therapy with neuroleptics. They received randomly, on a double-blind basis, fluoxetine (20 mg/day) or placebo for 12 weeks. In the fluoxetine group, three patients dropped out because of side effects. Negative symptoms, as measured by change on the Scale for Assessment of Negative Symptoms at the end point compared to baseline values, were significantly improved in fluoxetine-treated patients (p < 0.001), but not in the placebo group. Fluoxetine treatment did not influence positive schizophrenic symptoms, while it induced a slight, but statistically significant, decrease (p < 0.05) in depressive symptoms, as measured by the Hamilton Rating Scale for Depression. Unwanted effects were more common among patients receiving fluoxetine. These data suggest that the addition of fluoxetine to neuroleptic treatment may be beneficial in some schizophrenic patients with negative symptoms. PMID- 7868851 TI - Correlation between prolactin response and therapeutic effects of zotepine in schizophrenic patients. AB - The correlation between prolactin response and therapeutic effects of zotepine, as assessed by the Brief Psychiatric Rating Scale, was studied in 24 schizophrenic patients (12 males, 12 females), after 4 weeks of treatment. The daily dose was 100 mg in the first week, and 200 mg for the next 3 weeks. There were significant (p < 0.05) positive correlations between changes in serum prolactin concentration and amelioration scores of positive or total symptoms in males only. Thus, prolactin response may reflect therapeutic effects of zotepine, at least in males. PMID- 7868852 TI - Dopamine increases platelet intracellular calcium in bipolar affective disorder and controls. PMID- 7868853 TI - Two cases of fleroxacin-induced insomnia. PMID- 7868854 TI - Immunocytochemical localization of platelet-type arachidonate 12-lipoxygenase in mouse blood cells. AB - Arachidonate 12-lipoxygenase is an enzyme that oxygenates the 12 position of arachidonic acid to produce its 12-hydroperoxy derivative. We were interested in the tissue distribution and subcellular localization of the platelet-type 12 lipoxygenase, which is distinguished from the leukocyte type by several criteria. Antiserum was raised in rabbits against purified recombinant arachidonate 12 lipoxygenase of human platelets. When mouse bone marrow cells and lung were immunostained and observed by light and electron microscopy, the positively stained cells were platelets, megakaryocytes, and eosinophils. 12-Lipoxygenase was localized in the cytoplasm of platelets but was hardly detectable in the plasma membrane and intracellular organelles. The enzyme was found in the cytoplasm of immature megakaryocytes with kidney-shaped nuclei and a few profiles of demarcation membranes, as well as in the mature form with well-developed demarcation membranes. These results indicated the expression of 12-lipoxygenase at an early stage in the course of megakaryocytopoiesis. PMID- 7868856 TI - Alterations in hyaluronan synthesis during developing joint cavitation. AB - The mechanisms essential for generating diarthrodial joint cavities between skeletal elements in developing limbs remain enigmatic. Histochemical localization of hyaluronan (HA) at joint interzones concomitant with cavitation led to the postulation that HA may be pivotal in this process. HA synthesis involves the transfer of UDP-glucuronate and UDP-N-acetyl glucosamine to nascent HA by HA synthase. Uridine diphosphoglucose dehydrogenase (UDPGD) activity is responsible for the prior conversion of UDP-glucose to UDP-glucuronate. We have assessed the relationship between the appearance of HA and enzyme activities (quantitatively where possible) involved in HA synthesis during metatarsophalangeal joint development in embryonic chicks. Microspectrophotometric assessment of UDPGD activity using an in situ biochemical assay indicated that cells immediately adjacent to forming cavities contained increased UDPGD activity, which was subsequently maintained after cavitation. Immunocytochemistry showed that high levels of expression of HA synthase were localized to these same cells. In addition, radiolabeled sulfate autoradiography showed that cells bordering developing cavities incorporated relatively little sulfate, suggesting that UDP-glucuronate is utilized in the synthesis of undersulfated or non-sulfated glycosaminoglycans. These results indicate that the differentiation of cells bordering presumptive spaces may involve alterations associated specifically with differential synthesis of HA, which appears to be a primary event in joint cavity formation. PMID- 7868855 TI - Quantitative immunoelectron microscopic analysis of the localization and induction of 25-hydroxyvitamin D3 24-hydroxylase in rat kidney. AB - 25-Hydroxyvitamin D3 24(R)-hydroxylase (24-hydroxylase) is involved in the metabolism and regulation of vitamin D3 and is markedly induced by administration of vitamin D3. We detected this enzyme by electron microscopy and an immunogold technique along nephrons of normal and vitamin D3-administered rats. After the rats were administered vitamin D3, 50,000 IU/day for 1 week, they were perfusion fixed with a paraformaldehyde solution. The fixed kidneys were then removed and embedded in LR White resin. Ultrathin sections were prepared and labeled by the immunogold technique using a mouse anti-rat 25-hydroxyvitamin D3 24-hydroxylase monoclonal antibody. We counted the number of gold particles bound per micron 2 of the mitochondria (particle density) of the tubule epithelial cells along the nephrons. In normal and vitamin D3-administered rats, gold particles were observed in the mitochondria of epithelial cells along the tubules. In normal rats, gold labeling for 24-hydroxylase was statistically significant (p < 0.05), in the S1-S2 segments, the S3 segment of the proximal tubules, and in the distal convoluted tubules. In the rats administered vitamin D3, the particle density increased significantly (p < 0.05) by about 12-fold in the S1-S2 segments of the proximal tubules, whereas it increased less markedly in other parts of the nephron. The marked induction of the S1-S2 segments of the proximal tubules suggests that these segments play an important role in the regulation of vitamin D3 metabolism. PMID- 7868857 TI - Lectin-binding properties of human breast cancer cell lines and human milk with particular reference to Helix pomatia agglutinin. AB - Several studies have shown binding of a variety of lectins to breast cancer cells in tissue sections. In particular, binding of the lectin from the Roman snail, Helix pomatia agglutinin (HPA), to breast cancer cells is linked with a poor prognosis. The molecular basis for lectin binding to metastatic breast cancers is not known. To elucidate this in a model system, lectin-binding patterns of seven human breast cancer cell lines were investigated, their cell membranes were isolated, and HPA binding was assessed. In addition, the influence of fixation and processing on lectin-binding sites was also investigated. Binding of lectins to the tumor cells was very heterogeneous between and within the different cell lines and was influenced by fixation and processing. However, some cell lines showed HPA-binding sites both in vivo and in tissue sections. Analysis of the isolated cell membrane glycoproteins from these cell lines on Western blots revealed that HPA can bind to several membrane glycoproteins. In contrast, human milk shows only one major milk glycoprotein that is HPA-positive. Therefore, a switch in glycosylation appears to be taking place during the transformation to a metastatic phenotype. PMID- 7868858 TI - Association of malachite green-positive material with heparan sulfate proteoglycan double tracks in basement membrane of mouse kidney tubules. AB - The presence of lipids in the basement membrane of the mouse kidney tubules was examined by histochemical staining with malachite green. Pieces of mouse kidney cortex were immersed in a fixative containing 3% glutaraldehyde and 0.1% malachite green in 0.067 M sodium cacodylate buffer, pH 6.8, for 18 hr at 4 degrees C. Control tissue was fixed in the same way except that no malachite green was added to the fixative. The tissue pieces were cryoprotected, frozen in Freon 22, and subjected to freeze-substitution in dry acetone containing 1% OsO4. Thin sections of Epon-embedded specimens were observed by electron microscopy at first without uranyl-lead counterstaining. The basement membrane of mouse kidney tubules was positively stained in a pattern composed of an irregular assembly of 5-8-nm wide strands. The nature of these malachite green-positive strands was further examined by counterstaining thin sections with uranyl-lead, and they were identified as 4.5-5-nm wide ribbon-like "double tracks" previously characterized as the form taken by heparan sulfate proteoglycan in basement membranes. It is concluded that lipids are present in the basement membrane of mouse kidney tubules in association with heparan sulfate proteoglycan. PMID- 7868859 TI - Anionic sites on Reissner's membrane, stria vascularis, and spiral prominence. AB - We demonstrated anionic sites on the lateral wall of cochlear duct and Reissner's membrane (RM) of ICR mice by Lowicryl K4M resin post-embedding and poly-L-lysine colloidal gold conjugate (PL-CG) as a polycationic probe. The basement membrane and endolymphatic cell surface of RM were labeled with PL-CG pH 2.5 and pH 1.0. However, the perilymphatic cell surface was not labeled. PL-CG pH 2.5 and pH 1.0 strongly labeled the endolymphatic surface of the spiral prominence epithelium (SP), whereas the endolymphatic surface of the marginal cell (MC) in the stria vascularis was not labeled. Pre-digestion with several glycosidases eliminated PL CG labeling. Our result suggests that an anionic charge located on the basement membrane of RM is largely due to the presence of heparan sulfate, chondroitin sulfate, and hyaluronic acid. An anionic charge on the endolymphatic cell surface of RM was mainly dependent on the presence of heparan sulfate. An anionic charge on the SP epithelium was caused to a substantial degree by chondroitin sulfate. We obtained histochemical evidence that the glycoconjugate content of the MC surface was quite different from that of the endolymphatic cell surface of RM and SP. We also identified RM-MC and SP-MC junctions at the ends of the stria vascularis between the marginal cells and the other endolymphatic epithelial cells of the cochlear duct. PMID- 7868860 TI - Microwave fixation improves antigenicity of glutaraldehyde-sensitive antigens while preserving ultrastructural detail. AB - Microwave fixation for electron microscopy has been used primarily for post embedding immunocytochemistry. The present study examined the ability of microwave fixation to preserve the antigenicity of glutaraldehyde-sensitive antigens for pre-embedding immunocytochemistry. Five monoclonal antibodies (MAbs) directed against cell surface components of rat mast cells were tested. The MAbs failed to show any labeling of conventionally fixed rat bone marrow-derived mast cells even at glutaraldehyde concentrations as low as 0.1%. Strong staining of mast cell plasma membranes was seen when bone marrow was initially fixed with 2% formaldehyde and then refixed in 2% glutaraldehyde/2% formaldehyde after immunostaining. However, the ultrastructural preservation of the cells was poor. Antigenicity and morphological detail were both preserved when bone marrow was fixed in 0.05% glutaraldehyde/2% formaldehyde for 4 sec in a 550-W microwave oven. With this method, mast cells in various stages of maturation as well as cells that did not contain granules were immunoreactive. This method should prove useful with antigens from many different cell types that are sensitive to glutaraldehyde fixation. PMID- 7868861 TI - Immunohistochemical detection of T-cell subsets and other leukocytes in paraffin embedded rat and mouse tissues with monoclonal antibodies. AB - We describe a method for immunohistochemical localization of T-cells, CD4+ T cells, CD8+ T-cells, B-cells, activated lymphocytes, major histocompatibility complex (MHC) class II antigens, macrophages, dendritic cells, and granulocytes in rat and mouse tissue fixed in periodate-lysine-paraformaldehyde (PLP) and embedded in paraffin. Rat and mouse spleen and eyes were fixed in PLP for 18-24 hr, rapidly dehydrated, infiltrated under vacuum with paraffin at 54 degrees C, sectioned, and stained with appropriate monoclonal antibodies (MAbs). Sections of PLP-fixed, paraffin-embedded spleen were compared with acetone-fixed frozen spleen sections with respect to morphology and staining quality. Nine of 10 MAbs to rat antigens and eight of nine MAbs to mouse antigens stained paraffin sections equally or more intensely than frozen sections. The two MAbs that showed weaker staining still gave good staining on paraffin sections. Paraffin-embedded rat and mouse eyes were easier to section serially than frozen eyes, showed superior morphology, and individually stained cells were readily identified. Therefore, a combination of PLP fixation and low-temperature paraffin embedding permits detection of the major types of immune cell in rat and mouse tissues while maintaining good morphology, particularly in diseased, damaged, or delicate tissues. PMID- 7868862 TI - Using laser scanning confocal microscopy as a guide for electron microscopic study: a simple method for correlation of light and electron microscopy. AB - Anatomic study of synaptic connections in the nervous system is laborious and difficult, especially when neurons are large or have fine branches embedded among many other processes. Although electron microscopy provides a powerful tool for such study, the correlation of light microscopic appearance and electron microscopic detail is very time-consuming. We report here a simple method combining laser scanning confocal microscopy and electron microscopy for study of the synaptic relationships of the neurons in the antennal lobe, the first central neuropil in the olfactory pathway, of the moth Manduca sexta. Neurons were labeled intracellularly with neurobiotin or biocytin, two widely used stains. The tissue was then sectioned on a vibratome and processed with both streptavidin nanogold (for electron microscopic study) and streptavidin-Cy3 (for confocal microscopic study) and embedded in epon/araldite. Interesting areas of the labeled neuron were imaged in the epon/araldite blocks with laser scanning confocal microscopy and then thin-sectioned at the indicated depth for electron microscopic study. This method provides an easy, reliable way to correlate three dimensional light microscopic information with electron microscopic detail, and can be very useful in studies of synaptic connections. PMID- 7868863 TI - The use of electron microscopic immunocytochemistry with silver-enhanced 1.4-nm gold particles to localize GAD in the cerebellar nuclei. AB - Silver enhancement of small gold particles can be used with pre-embedding immunocytochemistry to analyze the distribution of label over cell organelles. We have developed a method that improves tissue morphology, has good penetration of reagents, and allows greater control of silver enhancement of 1.4-nm gold. In this study we analyzed the distribution of glutamic acid decarboxylase (GAD), a synthetic enzyme for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), in the cerebellar nuclei of the mouse. Pre-embedding immunocytochemistry was carried out on brain sections fixed with high concentrations of glutaraldehyde and sodium metabisulfite. After incubations with a monoclonal antibody to GAD and a 1.4-nm NanoGold-labeled secondary antibody, sections were silver-enhanced with N-propyl gallate as a reducing agent and MES as a new buffer system. In the cerebellar nuclei, GAD label was specifically localized in axon terminals over clusters of synaptic vesicles. These terminals formed axosomatic and axodendritic contacts. The majority of GAD-labeled terminals had cytological characteristics indicating their origin from Purkinje cells, which are known to contain GAD. PMID- 7868864 TI - A simple technique for preservation of fixation-sensitive antigens in paraffin embedded tissues: addendum. PMID- 7868865 TI - Bibliography of the current world literature in hypertension. PMID- 7868866 TI - Actions of angiotensin II on cerebral blood flow autoregulation in health and disease. PMID- 7868867 TI - Atrial natriuretic peptide in the Milan hypertensive rat and the Milan normotensive rat: plasma concentration and binding to renal glomeruli in young, adult and aged rats. AB - METHODS: Blood pressures were determined in Milan hypertensive (MHS) and Milan normotensive (MNS) rats at different ages. Mean blood pressure, plasma atrial natriuretic peptide (ANP) concentration and renal glomerular receptors numbers and affinities were determined in young (25-day-old), adult (60- to 80-day-old) and aged (300-day-old) rats. RESULTS: Mean blood pressures, always higher in the MHS than in the MNS rats, increased with age in both strains. Plasma ANP concentrations were similar in the young and aged rats of both strains, but were higher in the adult MHS than in the adult MNS rats. There were no quantitative differences in the ANP receptors between young and old rats of the two strains, but an increase in the maximal binding capacity was observed, in both strains, when adult rats were compared with young rats. Moreover, saturation experiments with [125I]-rat ANP revealed a downregulation of the ANP receptors in the renal glomeruli isolated from the adult MHS rats. In isolated glomeruli the cyclic GMP stimulation by ANP was similar in adult rats of both strains. CONCLUSION: Downregulation in glomeruli of MHS rats, probably involving the clearance receptors for ANP, is concluded to occur. PMID- 7868868 TI - Resting cardiovascular status and vasodilator function in a vasopressin deficient, hypertensive strain of rat. AB - OBJECTIVE: To assess resting haemodynamic status and vasodilator responses in normotensive vasopressin-deficient (DI/N) and hypertensive vasopressin-deficient (DI/H) rats. DESIGN AND METHODS: DI/N and DI/H rats were chronically instrumented with pulsed Doppler probes and intravascular catheters and were given 3-min infusions of acetylcholine (56 nmol/kg per min), bradykinin (36 nmol/kg per min) or salbutamol (2.1 nmol/kg per min) in the absence and presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 183 nmol/kg per min) or vasopressin (5 pmol/kg per min), to control for the pressor effects of L-NAME. RESULTS: The DI/H rats had a higher mean arterial blood pressure, lower hindquarters flow and lower vascular conductance than the DI/N rats. In the two strains of rat the haemodynamic responses to L-NAME, as well as to acetylcholine, bradykinin and salbutamol, in the absence or presence of L-NAME, were similar. In both strains of rat the acetylcholine-induced renal vasodilation was blocked by L-NAME, but bradykinin-induced mesenteric and salbutamol-induced hindquarters vasodilation involved L-NAME-sensitive and L-NAME-insensitive components. CONCLUSIONS: There is vasoconstriction in the hindquarters but not in renal and mesenteric vascular beds of DI/H rats. Vasodilator function is not necessarily impaired in congenital hypertension. PMID- 7868869 TI - Experimental hypertension produces diverse changes in the regional vascular responses to endothelin-1 in the rabbit and the rat. AB - OBJECTIVE: To examine the effects of hypertension on systemic and regional haemodynamic responses to endothelin-1. DESIGN: Comparison of responses between age-matched control and hypertensive rabbits (two-kidney, two wrapped), and between spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats. METHODS: Arterial pressure, heart rate and blood flow responses to 0.2 nmol/kg intravenous endothelin-1 were measured in conscious animals. Blood flow was measured by pulsed ultrasound Doppler in the ascending aorta, distal abdominal aorta, left renal artery and superior mesenteric artery. RESULTS: Endothelin-1 produced qualitatively similar effects in the hypertensive and control animals. In the systemic circulation, brief initial vasodilation preceded sustained vasoconstriction. In the hindlimb, marked vasodilation preceded relatively minor vasoconstriction, and profound vasoconstriction occurred in the renal and mesenteric vascular beds. In the rats but not the rabbits, fleeting vasodilation preceded the renal and mesenteric vasoconstriction. Significant differences between hypertensive and control animals were: accentuation of the pressor effect and heart rate responses in hypertensive animals of both species, and accentuation of hindlimb vasodilation in hypertensive rabbits but not SHR; and attenuation of the depressor effect in SHR but not hypertensive rabbits, attenuation of the mesenteric vasoconstriction in both hypertensive rabbits and rats, and attenuation of renal vasoconstriction in SHR. CONCLUSIONS: The increased responses to endothelin-1 of some variables in the hypertensive animals may involve structural changes in the resistance vessels. However, the reduced responses in the mesenteric vasculature of both species and the renal vasculature of the SHR are due to some mechanism other than structural change. PMID- 7868870 TI - Nitric oxide production by human umbilical vessels in severe pre-eclampsia. AB - OBJECTIVE: Pre-eclampsia is characterized by an increased vascular tone which might be related to an abnormal endothelial cell function. As representatives of the fetal circulation, we compared the nitric oxide (NO)-releasing capacity of human umbilical vessels from normal and pre-eclamptic pregnancies. METHODS: Normal and pre-eclamptic umbilical vessels were mounted in parallel in an organ chamber with three perfusion lines superfusing the same detector tissue (rubbed rat aortic ring). In this cascade system the capacity of the umbilical vessels to release NO was measured under basal conditions and after stimulation with histamine, bradykinin or calcium ionophore A23187. RESULTS: Relaxations dependent on basal NO release were found to be significantly higher in pre-eclamptic vessels (especially in veins) than in normal vessels. Conversely, stimulated NO release in response to histamine or bradykinin was significantly decreased in pre eclamptic umbilical arteries, but not in veins, compared with normal vessels. However, there was no significant difference in the release of NO in response to A23187 between normal and pre-eclamptic vessels. CONCLUSIONS: The NO-releasing and NO-producing capacity in the vessels from fetal circulation is not diminished in pre-eclampsia. However, in pre-eclamptic umbilical arteries the NO release in response to certain stimuli (histamine or bradykinin) is diminished, probably as a result of alterations in the receptor function. PMID- 7868872 TI - The influence of salt intake on plasma calcitonin gene-related peptide in subjects with mild essential hypertension. AB - BACKGROUND: Calcitonin gene-related peptide is a pleiotropic neuropeptide with potent vasodilatory properties, which interferes with renin release and might participate in cardiovascular homeostasis. DESIGN AND METHODS: We studied the influence of salt intake on the plasma concentration of calcitonin gene-related peptide, parathyroid hormone and on the renin-aldosterone system in 15 patients with mild hypertension. Each participant was studied after 1 week of high salt intake (200 mmol/day) and after 1 week of low salt intake (50 mmol/day). The order of the two diet periods was randomized and crossover. Plasma calcitonin gene-related peptide concentration was measured by radioimmunoassay after pre extraction by reverse chromatography. Seven patients were classified as salt sensitive and eight as salt-resistant. RESULTS: In the whole group the low salt intake caused a significant decrease in arterial pressure and the expected increase in plasma renin activity and in plasma aldosterone concentration. Such changes were accompanied by a significant increase in plasma calcitonin gene related peptide. In salt-resistant patients in the sodium-replete state calcitonin gene-related peptide levels tended to be reduced in comparison with salt-sensitive patients. Sodium depletion, however, caused a more pronounced rise in plasma calcitonin gene-related peptide in salt-resistant hypertensives, who attained levels close to those in salt-sensitive hypertensives. Interestingly, in salt-resistant hypertensives changes in plasma calcitonin gene-related peptide were closely related to plasma renin activity (r = 0.71, P = 0.003), whereas no such correlation was found in salt-sensitive patients. Parathyroid hormone was not influenced by changes in salt intake. CONCLUSIONS: In subjects with mild hypertension calcitonin gene-related peptide is sensitive to changes in salt intake in the physiological range. Such a response seems to be linked to the individual arterial pressure response to salt, because salt-resistant patients showed reduced calcitonin gene-related peptide levels in the sodium-replete state and a more pronounced calcitonin gene-related peptide increase, closely related to plasma renin activity, during sodium deprivation. PMID- 7868871 TI - Does lipophilicity of angiotensin converting enzyme inhibitors selectively influence autonomic neural function in human hypertension? AB - INTRODUCTION: Angiotensin II has both central nervous system and peripheral effects on autonomic function. Ramipril is among the more lipophilic angiotensin converting enzyme (ACE) inhibitors, and hence can penetrate the central nervous system readily. METHODS: We investigated whether rampiril has selective effects on autonomic control of the circulation in human hypertension, compared with the more hydrophilic ACE inhibitor enalapril. Blood pressure, hemodynamics and measurements of autonomic function were obtained in 13 essential hypertensive subjects after 10 days on placebo, and after crossover monotherapy with 10 days on enalapril versus 10 days on ramipril. RESULTS: Both enalapril and ramipril lowered systolic, diastolic and mean arterial blood pressures significantly, with no reflex increase in heart rate. Plasma renin activity increased substantially on each of the ACE inhibitors. There were no significant effects of either agent on plasma catecholamines (norepinephrine or epinephrine) or chromogranin A, biochemical indices of efferent sympatho-adrenal outflow. There were also no significant changes after either agent in baroreflex sensitivity (to high- and low-pressure stimuli), the response to cold stress or sympathetic (alpha adrenergic) participation in blood pressure maintenance. There was a marginal effect of ACE inhibition on alpha 1-adrenergic pressor sensitivity, but the two compounds did not differ significantly in this respect. CONCLUSION: Autonomic control of circulatory function was maintained well after either lipophilic (ramipril) or hydrophilic (enalapril) ACE inhibitors, and the lipophilic compound ramipril had no additional effects on autonomic function beyond those shown by the hydrophilic agent enalapril. PMID- 7868873 TI - Blunted inhibition by insulin of agonist-stimulated calcium, pH and aggregatory responses in platelets from hypertensive patients. AB - INTRODUCTION: Insulin may influence platelet function by modulating platelet responsiveness to vasoactive agonists. In essential hypertension platelet hyperactivity might be related to altered modulation by insulin. The present study examined the effects of physiological concentrations of insulin on agonist stimulated platelet responses [free calcium concentration, intracellular pH (pHi) and thrombin-induced aggregation] in platelets from 30 normotensive subjects and 53 untreated essential hypertensive patients. METHODS: Platelet free calcium concentration and pHi were measured spectrofluorometrically using specific fluorescent dyes [Fura-2/acetoxymethyl ester and 2',7'-bis-(carboxyethyl)-5(6) carboxyfluorescein/acetoxymethyl ester, respectively] in unstimulated and in angiotensin II (Ang II; 1 nmol/l)- and endothelin-1 (1 nmol/l)-stimulated platelets that had been pre-exposed to insulin (70 microU/ml). Aggregatory responses were measured turbidometrically in platelets stimulated by thrombin (0.05 U/ml), alone or in combination with angiotensin II or endothelin-1 in the absence and presence of insulin pre-incubation. RESULTS: Blood pressure and serum glucose and insulin levels were significantly elevated in the hypertensive patients. Basal and agonist-stimulated free calcium concentration, pHi and aggregation were significantly higher in the hypertensive than in the normotensive group. In platelets pre-exposed to insulin for 5 min, agonist induced responses were significantly reduced (by 40-60%) in the normotensive group but not in the hypertensive group. Serum insulin was positively correlated with Ang II-stimulated cytosolic free calcium concentration (r = 0.47, P < 0.01) and pHi (r = 0.26, P = 0.047) in platelets pre-exposed to insulin. CONCLUSIONS: This study demonstrates that insulin inhibits Ang II- and endothelin-1-stimulated platelet free calcium concentration and pHi, and thrombin-induced aggregation. In hypertension these insulin-related inhibitory effects are blunted. Attenuated inhibition of agonist-stimulated platelet responses by insulin could be a manifestation of peripheral insulin resistance which may contribute to platelet hyperactivity in essential hypertension. PMID- 7868874 TI - Impaired glucose tolerance in hypertension is associated with impaired insulin release independently of changes in insulin sensitivity. AB - OBJECTIVE: To assess the contribution of insulin release and glucose disposal by insulin-dependent and insulin-independent mechanisms to overall glucose tolerance in hypertension. DESIGN AND METHODS: Minimal model analysis of insulin and glucose data from frequently sampled intravenous glucose-tolerance tests from 21 non-diabetic, newly diagnosed hypertensives, and from 21 age- and weight-matched normotensive controls, was performed to obtain indices of glucose tolerance, beta cell function and insulin sensitivity. RESULTS: Intravenous glucose tolerance (defined as the glucose disappearance rate constant) was significantly correlated with the minimal model parameters for insulin sensitivity, glucose effectiveness or insulin-independent glucose uptake, and first- and second-phase beta-cell responsiveness (phi 1 and phi 2). First-phase insulin release, expressed either as the area under the insulin-time curve between 0 and 10 min or as the ratio of that area to total insulin area was also correlated with glucose tolerance. Despite similar basal insulin and glucose concentrations, glucose tolerance was clearly diminished among the hypertensives. This could not be accounted for by insulin resistance or by changes in insulin-independent glucose uptake. Insulin release was diminished, as evidenced by the lower phi 2 among the hypertensives. phi 2 was inversely correlated with systolic (r = -0.44, P < 0.003) and diastolic (r = -0.42, P < 0.006) blood pressures. These differences were independent of body weight. Hypertensives also exhibited a lower fractional clearance rate for insulin. CONCLUSION: Impaired insulin release might contribute to the glucose intolerance associated with hypertension, and this can occur in the absence of insulin resistance, which is not present in all subjects with essential hypertension. PMID- 7868875 TI - Angiotensin II type 1 receptor messenger RNA levels in human blood cells of patients with primary and secondary hypertension: reference to renin profile. AB - OBJECTIVES: The relationship between plasma renin activity, plasma angiotensin II (Ang II) or aldosterone levels and peripheral blood cells (mononuclear leucocytes and platelets) Ang II type 1 (AT1) receptor messenger RNA (mRNA) levels were examined in both primary and secondary hypertensive patients. DESIGN AND METHODS: The subjects were 30 patients with primary hypertension, five with primary aldosteronism, five with renovascular hypertension and five normotensive controls with renal cell carcinoma. Blood was collected from each patient for estimation of plasma renin activity and plasma Ang II and aldosterone concentrations, and for isolation of mononuclear leucocytes and platelets, which were then used to measure AT1 receptor mRNA with reverse-transcription polymerase chain reaction. RESULTS: Platelet AT1 receptor mRNA levels were inversely correlated with plasma Ang II levels, and mononuclear leucocyte receptor mRNA levels were positively correlated with plasma Ang II levels in patients with primary hypertension. In contrast, in secondary hypertension both platelets and mononuclear leucocytes AT1 receptor mRNA, which were elevated, were reduced after removal of the adrenal tumour or correction of stenosis of the renal artery. CONCLUSIONS: Platelet AT1 receptors, which were used to reflect physiologically important sites such as vascular smooth muscle, were shown to be regulated in a different manner from mononuclear leucocyte receptors. In patients with primary aldosteronism and renovascular hypertension the plasma aldosterone level was shown to be an important factor upregulating AT1 receptor mRNA. PMID- 7868876 TI - Endogenous opioid system and atrial natriuretic factor in normotensive offspring of hypertensive parents at rest and during exercise test. AB - OBJECTIVE: To investigate the effects of the endogenous opioid system on plasma atrial natriuretic factor (ANF) levels during sympathetic hyperactivity. DESIGN: We studied the young normotensive offspring of parents who both had essential hypertension, who are characterized by a hyperactive sympathetic nervous system. METHODS: We assessed plasma beta-endorphin, met-enkephalin, dynorphin B, ANF and noradrenaline levels, blood pressure and heart rate values in eight normotensive offspring and in 10 young normotensive subjects with no family history of hypertension (controls) at rest and during two exercise tests: the first test performed with the infusion of placebo (1.5 ml/min saline) and the second test with the infusion of an opioid antagonist (9.5 micrograms/kg per min naloxone hydrochloride). ANF and opioids were radioimmunoassayed after chromatographic pre extraction. RESULTS: At rest plasma met-enkephalin, dynorphin B, ANF and noradrenaline values in the normotensive offspring were significantly higher than in the controls. Exercise with placebo significantly raised all hormonal and haemodynamic parameters in the two groups. This increase was significantly higher in the normotensive offspring than in the controls. Naloxone did not modify any parameter in either group at rest, but it enhanced further the rise in plasma noradrenaline levels induced by exercise in both groups. A similar effect of naloxone during exercise was observed for plasma ANF levels in the normotensive offspring. CONCLUSIONS: Our findings show that plasma met-enkephalin, dynorphin B, ANF and noradrenaline levels at rest and during exercise are higher in normotensive offspring than in controls. The effects of naloxone indicate that in normotensive offspring at rest the opioid system does not affect ANF release, whereas during exercise it attenuates ANF hypersecretion, possibly by reducing noradrenaline release. PMID- 7868877 TI - Muscle sympathetic nervous system activity in black and Caucasian hypertensive subjects. AB - OBJECTIVE: To compare muscle sympathetic nerve activity (MSNA) in age- and weight matched African-Americans and American Caucasians with primary hypertension. DESIGN: Using microneurography, we compared MSNA at rest and in response to cold pressor testing and handgrip exercise in 13 hypertensive African-Americans and 12 hypertensive American Caucasians. METHODS: All subjects were withdrawn from antihypertensive medications for at least 2 weeks before the study. MSNA was recorded from the left peroneal nerve. RESULTS: Resting MSNA was similar in the Blacks and the Caucasians. Increases in muscle efferent activity, mean arterial pressure and heart rate in response to the cold pressure and handgrip exercise were not significantly different in Black and in Caucasian subjects. CONCLUSION: MSNA, either at rest or in response to certain laboratory stressors, is not different in Black and in Caucasian hypertensive subjects with similar resting blood pressures. PMID- 7868878 TI - The failure of malignant hypertension to decline: a survey of 24 years' experience in a multiracial population in England. AB - INTRODUCTION: The widespread use of antihypertensive medication and the increasing frequency of diagnosis of mild-to-moderate hypertension should mean that malignant-phase hypertension should be becoming less common, and this trend has been reported elsewhere. No decline in the incidence of malignant hypertension has been apparent in our practice in a district general hospital in a city centre. OBJECTIVE AND METHODS: To investigate the incidence and mode of clinical presentation of patients presenting with malignant hypertension, we performed a retrospective survey of the number of patients presenting with malignant hypertension to our hospital, over the 24-year period from 1970 to 1993. We identified a total of 242 patients (155 male, 87 female; mean +/- SD age 50.1 +/- 13.3 years) with malignant hypertension. RESULTS: There were no significant differences in the number of patients presenting each year, the mean age or the presenting systolic and diastolic blood pressures over the period surveyed. At presentation, 131 patients (54.1%) had no previous history of hypertension; 161 (66.5%) were receiving no antihypertensive therapy and only 70 (28.9%) were receiving antihypertensive treatment (with no record of therapy in 11 patients). The most common presenting symptoms included visual disturbance in 62 (25.6%), headaches in 29 (12.0%), headaches and visual disturbance in 24 (9.9%), heart failure in 19 (7.9%), stroke or transient ischaemic attack in 17 (7.0%) and dyspnoea in 13 (5.4%), although 23 patients (9.5%) were asymptomatic. The most common presenting complications were heart failure [27 patients (11.1%)], stroke [23 patients (9.5%)], angina [10 patients (4.1%)], myocardial infarction [nine patients (3.7%)] and chronic renal failure [77 patients (31.7%)]. In the whole group the majority (147 patients, 60.5%) had no complicating clinical features. Primary or essential hypertension was the most common underlying cause in 137 patients (56.4%). Secondary causes of hypertension (mainly renal disease) were identified in 97 patients (39.9%). CONCLUSION: Our experience suggests that malignant hypertension is still common, with a small proportion of hypertensives presenting each year. In particular, the incidence has failed to decline in Birmingham. The incidence rate in the population served by our hospital is approximately 1-2 cases per 100,000 per year. An awareness of the different presenting clinical features is required to allow better recognition and management of this life-threatening condition. PMID- 7868879 TI - AD2, a human molecule involved in the interaction of T cells with epidermal keratinocytes and thymic epithelial cells. AB - Interactions between T cells and epithelial cells of the thymus are essential for normal T cell development, and interactions between T cells and skin epidermal keratinocytes occur in the context of inflammatory skin diseases and cutaneous T cell malignancies. On the basis of observations that the T cell ALL cell line, HSB, bound to IFN-gamma activated epidermal keratinocytes (41 +/- 5% of EK with three or more HSB cells bound), whereas the CTCL cell line H9 bound poorly (8 +/- 3%), we have raised mAb 13H12 that identified a 36 kDa molecule, termed AD2, that was highly expressed on HSB but not on H9 T cells. mAb 13H12 inhibited the binding of HSB T cells to IFN-gamma-treated epidermal keratinocytes (43 +/- 5% inhibition, p < 0.01), inhibited the binding of peripheral blood T cells to IFN gamma-treated EK (62 +/- 3% inhibition, p < 0.001), and inhibited the binding of IFN-gamma-treated human thymic epithelial cells to thymocytes (39 +/- 3% inhibition, p < 0.01). Although AD2 was expressed at a low level on all T cells, AD2 was highly expressed on the CD3-CD4-CD8-, CD3-CD4low+ CD8-, and CD3-CD4+ CD8+ subsets of immature thymocytes in the thymic subcapsular and inner cortex. Taken together, these data suggest a role for the AD2 molecule in interactions of T cells with epithelial cells of skin and thymus. PMID- 7868880 TI - Ligand binding by the IL-2 receptor is modulated by intracellular determinants of the IL-2 receptor beta-chain. AB - The biologic actions of IL-2 are mediated by the IL-2R, a multisubunit receptor complex displayed on the surface of lymphocytes and select other hematopoietic lineages. The IL-2R exhibits multiple affinities for IL-2 that result from the monomeric (alpha), heterodimeric (alpha beta and beta gamma), and heterotrimeric (alpha beta gamma) assembly of different receptor subunits. In the present studies, we have used a series of IL-2R mutants in a transient mammalian expression system to investigate the potential role of intracellular receptor regions in the ligand-binding functions of the IL-2R. Analyses of chimeric and deletion mutants of the IL-2R beta subunit have revealed that its intracellular domain critically and selectively influences high affinity ligand binding mediated through the extracellular domains of the alpha beta-heterodimeric receptor. In contrast, intermediate affinity binding of IL-2 by beta gamma heterodimeric receptors exhibits no dependence on the cytoplasmic domain of IL-2 R beta. Further, co-expression of either a full-length or severely truncated form of IL-2 R gamma to generate an alpha beta gamma-heterotrimeric complex also overcomes the functional dependence upon the cytoplasmic tail of IL-2 R beta. Collectively, our findings suggest that the cytoplasmic domain of IL-2R beta produces intrasubunit transmembrane conformational changes in this receptor subunit that promote extracellular IL-2 binding in combination with IL-2R alpha. These findings have important implications for the receptor dynamics involved in both ligand binding and signal transduction as well as for clinical applications pertaining to altering IL-2R function. PMID- 7868881 TI - Mitogen activation of a nuclear alkaline phosphatase in normal activated lymphocytes. AB - B cell differentiation is punctuated by V(D)J joining in the heavy chain of the pro-B cell, VJ joining in the light chain of the pre-B cell, switch recombination, and somatic hypermutation in the mature B cell. The regulatory signals controlling these events and the developmental program leading to them is poorly understood. We have identified a new phosphatase activity that is expressed in lymphocytes and for which high expression is restricted to mature B cells. This new phosphatase is transiently expressed in nuclear extracts of mitogen-activated splenic B cells. The phosphatase is a monoesterase that is active on both dNMPs and pNPP. The phosphatase has been partially purified by column chromatography and is inhibited by orthovanadate, molybdate, tetramisole, and EDTA and requires Mn2+ for activation. Monoesterase activity requires a pH above the neutral range. The activity profile in the presence of the inhibitors and the requirement for basic pH suggest that this enzyme is an alkaline phosphatase. PMID- 7868882 TI - Early appearance of "natural" mucosal IgA responses and germinal centers in suckling mice developing in the absence of maternal antibodies. AB - We have examined the role of passively transferred maternal Abs in the ontogeny of "natural" mucosal IgA responses before weaning of suckling mice by comparing the immune status of gut-associated lymphoid tissue (GALT) (Peyer's patches, mesenteric lymph nodes, and lamina propria) in 7- to 25-day-old F1 severe combined immunodeficient (scid)/+ mice generated through reciprocal crosses of C.B17 scid/scid and normal congenic (+/+) adult mice. We have also examined the ability of prenatal vs postnatal transfer of maternal immunity to forestall the development of natural neonatal mucosal IgA responses by swapping litters of F1 scid/+ pups at birth between +/+ and scid/scid mothers. Our results demonstrate that F1 scid/+ pups born to or nursed by scid/scid mothers undergo an accelerated development of natural IgA responses that include germinal center reactions in both Peyer's patches and mesenteric lymph nodes. These early IgA responses are evident as: 1) increased frequencies of IgA-producing GALT organ cultures; 2) increased mean IgA output by GALT organ cultures; 3) increased frequencies (> 1 log) of IgA-secreting cells from GALT detected by ELISPOT at 16 days of age; and 4) germinal center development by 17 days of age detected by in vivo bromodeoxyuridine incorporation. Finally, FACS analyses of enteric bacteria isolated from F1 scid/+ pups and stained for the presence of surface-bound mouse IgA demonstrate that the bacterial flora is a major target of both maternal secretory IgA and of the earliest IgA Abs produced in the neonatal GALT of pups deprived of maternal immunity. PMID- 7868883 TI - Decreased CD4-CD8- TCR-alpha beta + cells in lpr/lpr mice lacking beta 2 microglobulin. AB - The CD4-CD8- T cells that accumulate in lpr/lpr mice have previously expressed CD8, on the basis of studies of CD8 alpha gene demethylation. The actual requirement for CD8 interaction with class I MHC molecules to promote the appearance of CD4-CD8- T cells in lpr/lpr mice has also been suggested. To examine this point in more detail, the lpr mutation was bred onto a beta 2 microglobulin-deficient background (beta 2-m-/-). C57BL/6 (B6) mice homozygous for both the lpr mutation of the fas gene and inactivation of the beta 2-m gene (beta 2-m-/- lpr/lpr) develop less alpha beta T cell lymphadenopathy than the parental B6 lpr/lpr strain. This is caused by the near absence of CD8+ T cells and a considerable reduction in CD4-CD8- T cells, revealing an important role for positive selection on class I MHC molecules during the ontogeny of lpr CD4-CD8- T cells. Although absolute numbers of peripheral T cells are decreased in beta 2-m /- lpr/lpr mice, they manifest a B cell lymphadenopathy with age. beta 2-m-/- lpr/lpr mice display only subtle indications of autoimmune disease with age, compared with parental B6 (beta 2-m+/+)lpr/lpr mice. These include limited histopathologic stages of kidney disease and lack of proteinuria, despite the presence of serum anti-DNA Abs. Thus, absence of class I MHC-positive selection of CD8+ and CD4-CD8- TCR-alpha beta + cells limits the autoimmune diathesis observed in beta 2-m+/+ lpr/lpr mice. PMID- 7868884 TI - T cell receptor alpha-chain defines the antigen specificity of antigen-specific suppressor factor but does not impart genetic restriction. AB - Previous studies utilizing NP (4-hydroxy, 3-nitrophenyl acetyl hapten)-specific, T suppressor hybridomas have indicated that expression of TCR-alpha, but not TCR beta, mRNA is required for expression of Ag-specific suppressor factor bioactivity. Suppressor-effector factor has been shown to be Ag specific and I-J restricted. Although the expression of TCR-alpha mRNA was necessary for suppressor activity, the role of TCR-alpha, as it pertained to the functional properties of T cell suppressor factor (TsF), was not established. To determine which properties of TsF could be accounted for by TCR-alpha expression, TCR-alpha cDNA, derived from NP-specific, suppressor T cell (Ts) hybridomas, was transfected into recipient Ts hybridomas of a second Ag specificity. The resulting heterologous transfectants displayed NP-specific, genetically restricted TsF activity. The Ag specificity corresponded to that of the TCR-alpha donor; however, the genetic restriction was influenced by the recipient cell, implying that TCR-alpha did not control genetic restriction of the TsF. Examination of TCR-beta expression in one of the MHC-restricted transfectants indicated that the genetic restriction of TsF could not be accounted for by TCR beta gene products. The data support the conclusion that TCR-alpha expression is not only obligate for TsF bioactivity, but that the Ag specificity of the TCR alpha dictates the Ag specificity of the resulting suppressor factor. PMID- 7868885 TI - Perturbation of B cell genesis in the bone marrow of pristane-treated mice. Implications for plasmacytoma induction. AB - A single injection of pristane was given i.p. to plasmacytoma-susceptible BALB/cAn mice. At intervals up to 6 mo thereafter, immunofluorescence labeling of intranuclear terminal deoxynucleotidyl transferase (TdT), cell surface B220 glycoprotein, cytoplasmic mu-chains of IgM (c mu), and surface mu-chains (s mu), together with mitotic arrest techniques, were used to quantitate the in vivo population dynamics of precursor B cells in the bone marrow. TdT-expressing pro-B cells (TdT+B220-, TdT+B220+), before the expression of mu-chains, showed sustained increases in both population size and the number of cells flowing through mitosis per unit time. In contrast, populations of pre-B cells (c mu + s mu -) and B cells (s mu +) were consistently depressed for long periods of time, including the phase of plasmacytoma formation. Precursor B cells in DBA/2 mice, a plasmacytoma-resistant strain, showed similar responses to pristane treatment. The results demonstrate that a single injection of pristane, which greatly increases the demand for macrophage activity in the peritoneal space, causes sustained distant alterations in B cell lymphopoiesis in the bone marrow; specifically, a prolonged increased proliferation of pro-B cells coupled with a depression and a exaggerated loss of pre-B cells and B cells. The protracted stress on B cell lymphopoiesis may be a predisposing factor in the subsequent development of c-myc-activating chromosomal rearrangements that play a critical role in plasmacytomagenesis. PMID- 7868886 TI - B cell superstimulatory influenza virus (H2-subtype) induces B cell proliferation by a PKC-activating, Ca(2+)-independent mechanism. AB - The influenza virus hemagglutinin glycoprotein (HA) induces a vigorous B cell proliferation and Ig-synthesis by an unknown activation mechanism, which is susceptible to the inhibitory effects of anti-Ig and anti-class II mAbs. To gain further insight into the activation mode of this T cell-independent, B cell "superstimulatory" virus, we analyzed the sensitivity of H2-subtype virus mediated B cell activation to the inhibitory effects of various signal transduction-blocking agents and compared it to the well characterized anti-mu mediated and the LPS-employed pathway. Cyclic-AMP agonists (cAMP-analogues, pentoxifylline, cholera toxin, and forskolin) blocked HA-mediated activation of B cells only at concentrations at least 50-fold higher than required for blocking of anti-mu-induced activation. However, HA-treatment failed to induce an increase in intracellular cAMP levels in responding B cells. The B cell response to HA was highly resistant to calcineurin-inhibitory cyclosporin-A treatment and did not result in a measurable Ca2+ influx. Similarly, HA failed to induce an increase in tyrosine phosphorylations, including phosphorylation of phospholipase C gamma 2. HA-activated B cells showed an increase in membrane-associated protein kinase C activity, and depletion of protein kinase C by pretreatment of B cells with phorbol esters inhibited a subsequent activation by HA. Collectively, our results provide a new example of B cell stimulation by multivalent type-2 Ags, which seems to be mediated by a phosphatidylinositol- and Ca(2+)-independent signaling pathway. PMID- 7868888 TI - Murine minor histocompatibility antigens detected by helper T cells. Recognition of an endogenous peptide. AB - Minor histocompatibility (H) Ags, encoded by autosomal and sex-linked genes, have classically been identified by the cytolytic T lymphocyte response to class I bound minor H Ags. A limited number of studies have identified minor H Ags (defined by congenic strains) that stimulate Th cells. We have selected a panel of minor H Ag-specific, CD4+ Th hybrids by the fusion of a BW5147 variant with a C57BL/6 anti-BALB.B T cell line. Studied hybrids secrete IL-2 following stimulation with BALB.B spleen cells and stimulation is blocked with anti-I-Ab Ab. These Th hybrids recognize a minimum of six different Ags (helper T target (HTT)) encoded by independently segregating genes as defined by stimulator cells from 11 CXB recombinant inbred strains. The CXB strain distribution patterns of detected Ags did not match the distribution pattern of the BALB/c MTV6 viral genome indicating that none of the detected Ags were known viral superantigens. Four tested HTT Ags appeared not to be acquired by stimulators as exogenous Ags as BALB.B spleen cells but not a mixture of BALB/c spleen cells and C57BL/6 APC stimulated IL-2 production by the respective Th hybrids. To determine whether Th hybrids recognized peptides bound to I-Ab, I-Ab molecules were immunoprecipitated from the LB27.4 cell line that stimulated the A6.5.5 hybrid (HTT-4 specific). Peptides were extracted from I-Ab molecules, ultrafiltered, and separated by HPLC. A single fraction (with flanking peaks of lower activity) sensitized syngeneic APC to stimulate A6.5.5 hybrid cells; sensitization was observed at pH 5.0 but not pH 7.0, consistent with HTT-4 peptide:I-Ab binding occurring in an endosomal compartment. These observations indicate that at least one class II restricted minor H Ag is recognized by Th cells as a peptide bound to class II molecules. PMID- 7868887 TI - Regulation of lymphocyte pseudopodia formation by triggering the integrin alpha 4/beta 1. AB - Video microscopy and digital imaging were used to quantitatively analyze lymphocyte adhesion and formation of pseudopodia on the extracellular matrix protein fibronectin (FN). A morphology kinetics assay comparing pseudopodial extension values over a 24-h period showed that HPB-ALL T leukemic cells undergo a wave of morphologic change, returning to a round shape after 8 h. Using anti alpha 4 and anti-alpha 5 mAbs and a panel of cell types that are single or double positive for expression of the alpha 4/beta 1 and alpha 5/beta 1 FN binding integrins, it was determined that cell adhesion to FN was influenced by both beta 1-integrins, whereas alpha 4/beta 1 was found to be the major FN receptor mediating pseudopodia extension. The protein kinase inhibitor staurosporine, the protein kinase C inhibitors calphostin C and chelerythrine, and the protein tyrosine kinase inhibitor herbimycin A blocked pseudopodial extension in HPB-ALL cells. In contrast, two cAMP-dependent protein kinase inhibitors H8 and H89 did not inhibit. Inhibitors of phospholipase A2, lipoxygenases, and cyclooxygenases could block formation of pseudopodia, yet had little or no effect on cell adhesion to FN. The preincubation of cells with arachidonic acid could prevent the inhibition mediated by the reversible phospholipase A2 inhibitor cibacron blue. We conclude that the formation of lymphocyte pseudopodia in response to FN can utilize the adhesive and signaling activities of the alpha 4/beta 1-integrin and the enzymatic activities of protein kinases and phospholipases. PMID- 7868889 TI - Restoring the apoptosis suppression response to IL-5 confers on erythroleukemic cells a phenotype of IL-5-dependent growth. AB - We have established a human IL-5 (hIL-5) dependent cell line, JYTF-1, derived from TF-1 parental human erythroleukemic cells by long-term cultivation in the presence of hIL-5. The ED50 values of hIL-5 for both TF-1 and JYTF-1 cell lines remained similar. However, when cells were grown in an optimal concentration of IL-5, some TF-1 cells but not JYTF-1 cells died via apoptosis. Although the rates of DNA synthesis were similar for TF-1 and JYTF-1 cells grown in IL-5, [3 H]thymidine releasing of pulse-labeled DNA analysis indicated that the viable TF 1 cells in IL-5 were more apoptosis-prone than were JYTF-1 cells. Therefore, in the JYTF-1 variant, the ability to suppress apoptosis has apparently been restored. The following findings suggest that overexpression of the hIL-5 receptor alpha-chain may be responsible for restoring the apoptosis suppression ability of IL-5: 1) the growth of JYTF-1 cells remained cytokine-dependent; 2) the proliferation of JYTF-1 cells in IL-5 was not mediated by autocrine secretion; 3) JYTF-1 and TF-1 cells responded similarly to other cytokines such as human erythropoietin; 4) Northern blot analysis revealed that JYTF-1 cells expressed approximately eightfold more IL-5 receptor alpha-chain mRNA than did TF 1. To our knowledge, JYTF-1 represents the first example in which coupling of mitogenesis stimulation and apoptosis suppression from otherwise uncoupled parental cells confers a phenotype of IL-5-dependent growth. PMID- 7868890 TI - Transgenic control of perforin gene expression. Functional evidence for two separate control regions. AB - Perforin is a pore-forming effector molecule of CTL and NK cells. To characterize perforin gene expression and its transcriptional control mechanisms in vivo, expression of a cell surface tag, i.e., human CD4, was driven by 5.1 kb of the murine perforin 5' flanking and promoter region in transgenic mice. Six out of seven transgenic lines expressed the perforin-tag hybrid gene at low to intermediate levels, depending on the integration site. Tissues not yet reported to contain perforin-expressing lymphocytes were identified. Transgene expression occurred in all cells that physiologically are able to express perforin, i.e., in T cells and NK cells, and in some T cells that normally may express little or no perforin. At the whole organ level, significant amounts of transgenic mRNA and endogenous perforin mRNA were co-expressed in the lymphoid organs, as well as in the lung, the ileum, the oviduct/uterus, and the bone marrow. At the single cell level, the perforin tag was present on NK cells and on CD8+, as well as on CD4+ T cells. Also targeted were Thy-1.2+ gamma delta T cells, but not Thy1.2- gamma delta T cells, B cells, nor monocytes. During thymic T cell development, transgene expression occurred in double negative (CD4-CD8-) thymocytes and was detected at all subsequent stages, but exceeded the expression levels of the endogenous gene in the thymus. In conclusion, the analyzed perforin 5' flanking and promoter region contains important cis-acting sequences that restrict perforin expression to T cells and NK cells, and therefore provides a unique tool for manipulating T cell and/or NK cell-mediated immune responses in transgenic mice. On the other hand, the normal control of perforin gene expression involves at least one additional negative control mechanism that was not mediated by the transgenic promoter and upstream region. This control restricts perforin gene expression in thymically developing T cells and in most resting peripheral T cells, but can be released upon T cell activation. PMID- 7868891 TI - Recombination potential of the human DIR elements. AB - The human DIR genes are putative DH elements that are GC rich and are found between DN and DM DH gene segments. The DIR genes each have consensus recombination signal sequences (RSS) that could conceivably generate DIR coding regions of about 126 nucleotides. These RSS should allow for DH-DH rearrangements that do not violate the 12/23 recombination rule. Several Ig CDR3 sequences have been assigned to DIR usage; however, there are frequent gaps and mismatches associated with these assignments. In some instances these CDR3 sequences might be better explained by GC rich N segment addition. This report analyzes the recombination potential of the human DIR elements by PCR. Though DH-JH rearrangement of the DH genes flanking the DIR regions (DM and DN) are easily demonstrated, very little evidence of DIR-JH rearrangement could be documented. Furthermore, in amplifications that should concurrently detect both DH-DIR rearrangements (which maintain the 12/23 recombination rule) and DH-DH rearrangements (which violate the 12/23 recombination rule), DH-DH rearrangements predominate. We conclude that the DIR-associated RSS participate minimally in both DH-DH and DH-JH rearrangement. In addition, we describe several conventional DH-DH rearrangement intermediates, demonstrating unequivocally that this phenomena occurs during human Ig rearrangement. PMID- 7868892 TI - Sequence constraints and recognition by CTL of an HLA-B27-restricted HIV-1 gag epitope. AB - Previous studies on the variation of an immunodominant HLA-B27-restricted HIV-1 gag p24 epitope (KRWIIL GLNK, amino acids 263-272) have demonstrated the persistence of variants recognized by CTL. Sequence comparisons of HIV isolates showed that this region is relatively conserved and as a consequence might restrict antigenic variation. To evaluate the possibility of HIV-1 to yield infectious mutants of this epitope that lack the ability to bind to HLA-B27 or escape HLA-B27-restricted CTL recognition, single-point mutations were constructed in the infectious molecular clone of HIV-1 Lai. Changes of arginine 264, the anchor amino acid for HLA-B27, to lysine or glycine resulted in infectious HIV-1 variants. The respective synthetic peptides showed reduced ability to sensitize target cells for CTL recognition and a corresponding loss of binding affinity to HLA-B27. In contrast, mutation of glycine 269 to lysine or glutamate abrogated HIV-1 infectivity. The corresponding peptides were able to bind to HLA-B27 but were not recognized by CTL. These data show that HIV-1 tolerates some genetic variation of the HLA-B27-restricted CTL epitope in gag p24 and that single-point mutations can alter quantitatively the immunologic properties. Further, it demonstrates that the mere nonrecognition of peptides derived from quasispecies analysis of small regions might simply correspond to nonviable virus variants and cannot be taken as evidence for CTL escape mutants. Together with the previously published data on the persistence of CTL epitopes, these results suggest that CTL do not play a major role in driving HIV-1 evolution in vivo. PMID- 7868893 TI - Domain interactions and antigen binding of recombinant anti-Z-DNA antibody variable domains. The role of heavy and light chains measured by surface plasmon resonance. AB - The heavy (H) and light (L) chain V domains of anti-Z-DNA mouse mAb Z22 were expressed separately in bacteria. When mixed in vitro, the V domains associated stoichiometrically to reconstitute the Ag binding site of Z22, as judged by specific reactivity with Z-DNA and anti-Z22 ld Abs. The apparent Kd of the Z22 VH VL association was 5.47 x 10(-8) M, measured by surface plasmon resonance. A replacement at VL position 96, which reduced Ag binding affinity of a single chain Fv (clone LZ1-2) by two orders of magnitude, did not reduce the affinity of interaction between the VH and VL domains (apparent Kd = 1.93 x 10(-8) M for VH association with LZ1-2). Fab prepared from native Z22 bound specifically to a 30 bp Z-DNA oligonucleotide with an apparent Kd = 1.56 x 10(-8) M. The VH domain alone bound Z-DNA specifically with an affinity similar to that of the Fab or Fv's of Z22 (Kd = 1.68 x 10(-8) M), whereas Z22 VL domain alone did not interact with nucleic acids. Z22 VH binding to Ag was inhibited by association with the mutant LZ1-2 VL. These results indicate that the Z22 H chain makes important contributions to specific binding of Z-DNA. Although the L chain does not add greatly to the binding energy, an appropriate L chain is required to permit Ag binding in the Fv domain. These in vitro results resemble the in vivo modulation of H chain autoreactivity that occurs with L chain substitution in receptor editing. PMID- 7868894 TI - Binding analysis of antibodies produced by precursor and branchpoint intermediates of an anti-influenza hemagglutinin B cell clone. Parallel replacement mutations do not confer increased avidity for hemagglutinin. AB - We have previously described a set of secondary (2 degrees) hybridomas that are specific for the Sb site of influenza hemagglutinin (HA(Sb)) and share the H37-68 ld (68ld). Cells producing 68ld Abs dominated the 2 degree response of one BALB/c mouse, but were virtually absent from the primary (1 degree) and 2 degree responses of other BALB/c mice. To understand the basis for the idiosyncratic nature of this response, we have assessed the functional importance of a conserved DJ junctional sequence. We find that substitutions of conserved residues within this sequence drastically reduced HA(Sb) binding, providing an explanation for the absence of this ld from 1 degree responses. We have also examined intraclonal affinity maturation by generating Abs inferred to have been produced by the unmutated precursors and branchpoint intermediates of the largest 68ld clone. Interestingly, unmutated Abs of this clone bound HA(Sb) well, comparable to that of some 2 degree 68ld hybridoma Abs. Abs produced by branchpoint intermediates of this clone have a lower affinity for HA(Sb) than their unmutated precursor, despite containing parallel amino acid replacement mutations. Thus, expansion of this clone did not follow the paradigm of stepwise increases in affinity. Together, these data underscore the interconnective nature of precursor frequency and somatic mutation in the formation of the 2 degree response to a given Ag. PMID- 7868895 TI - Regulatory regions 3' of the immunoglobulin heavy chain intronic enhancer differentially affect expression of a heavy chain transgene in resting and activated B cells. AB - We have compared the expression patterns of three Ig heavy chain transgenes. The three constructs differ only by deletion of J-C intron sequences located downstream of the Emu enhancer region. When stably transfected into a myeloma cell line, all three constructs are expressed at comparable levels. However, transgenic mice carrying each construct show dramatic differences in transgene expression. Our results indicate that, in addition to the Emu enhancer, at least two regions, RegA and RegS, within the J-C intron influence transgene expression. RegA, located directly downstream of the core Emu enhancer, is involved in up regulation of transgene expression after LPS activation of splenocytes. RegS, located within or downstream of the Smu switch region, is important for normal levels of transgene expression in splenocytes of heavy chain transgenic mice. PMID- 7868896 TI - Addition of a mu-tailpiece to IgG results in polymeric antibodies with enhanced effector functions including complement-mediated cytolysis by IgG4. AB - The 18-amino acid carboxyl-terminal tailpiece from IgM (mutp) has now been added to the carboxyl-termini of IgG1, IgG2, IgG3, and IgG4 constant regions to produce recombinant IgM-like IgGs. Polymeric IgGs obtained by this approach possess up to six Fcs and 12 antigen-combining sites, greatly increasing the avidity of their interactions with other molecules. Not surprisingly, the C activity of normally active IgG1 and IgG3 and somewhat less active IgG2 Abs is shown to be dramatically enhanced upon polymerization. The multiple Fcs present in a single molecule apparently allow for more efficient interactions with the multiple C1q heads present in C1, the first component of the classical C cascade. An unexpected result however, is that IgG4, normally devoid of C activity, when polymerized in the same fashion directs C-mediated lysis of target cells almost as effectively as the other polymers. Interestingly though, IgG4mutp does not deplete C activity in a standard consumption assay using soluble Ag. The other gamma mutp isotypes are capable of depleting 100% of the serum lytic ability even in the absence of Ag, whereas IgG4mutp shows no evidence of activity in this assay under any of the conditions tested. Additionally, we show that, in contrast to monomeric IgG, polymeric IgGs bind with very high affinity to Fc gamma receptor II (Fc gamma RII), a low affinity receptor for wild-type antibodies; however, binding to Fc gamma Rl, the high affinity receptor, appears to be unaltered. Finally, the in vivo t1/2 of the gamma mutp proteins is decreased relative to wild-type IgG, apparently because of rapid clearance of the polymeric fraction. PMID- 7868897 TI - Secondary deletional recombination of rearranged switch region in Ig isotype switched B cells. A mechanism for isotype stabilization. AB - Analysis of the Ig switch (S) region structure from many stable isotype-switched B cells reveals that the majority of the ultimate switch recombination sites are located at the 5' end, or even upstream of the 5' end of the Smu region. These findings strongly contrast with results from switch circle analysis which reveal that the primary switch recombination sites are preferentially distributed in the middle or at the 3' end of the Smu region. Secondary deletion within recombined chimeric S regions has been proposed as a mechanism to account for the different results. We directly tested whether secondary deletion of rearranged chimeric S regions indeed occurs in human cells. Circular DNAs representing secondary deletion events in gamma switched cells were isolated and characterized by using a specially designed PCR-based approach. Nucleotide sequence analysis revealed that all clones had the S gamma 1-Smu-S gamma 1 structure. Thus, these cloned fragments resulted from secondary deletion/recombination events within a chimeric Smu-S gamma 1 switch region, i.e., rearrangement between its 5' Smu and 3' S gamma 1. Analysis of the Smu region from stimulated B cells also revealed that some Smu regions undergo an internal deletion/rearrangement between the 5' and 3' ends. These results definitively demonstrate that secondary deletion/recombination of chimeric S regions of isotype-switched B cells occurs. Such secondary deletion/recombination events potentially can be responsible for isotype stabilization of switched B cells, as the active Ig gene may have an insufficient amount of retained chimeric switch sequence to serve as a substrate for further S-S recombination. PMID- 7868898 TI - Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1. AB - MART-1 is an Ag expressed on melanomas and melanocytes, and is recognized by the majority of HLA-A2-restricted tumor-specific tumor-infiltrating lymphocytes (TIL) from melanoma patients. In the present study we have analyzed 10 potential 9-mer epitopes containing the HLA-A2.1 binding motifs for their ability to induce melanoma-specific T cell lines. Antimelanoma CTL could be generated only with MART-1(27-35) peptide, which has been previously shown to be recognized by a majority of HLA-A2-restricted TIL. Anti-MART-1(35-43)-specific CTL could also be induced, but these T cells did not recognize melanoma cells. MART-1(27-35) specific CTL could be effectively generated from a total of 11 of 12 PBL and from 3 of 3 TIL derived from HLA-A2+ melanoma patients, as well as from 2 of 4 PBL from HLA-A2+ healthy donors by in vitro stimulation with autologous PBMC pulsed with the synthetic MART-1(27-35) peptide. These CTL lines specifically lysed and release cytokines (TNF-alpha, IFN-gamma, and GM-CSF) in response to T2 cells pulsed with MART-1(27-35), as well as to HLA-A2+ MART-1+ melanoma cells. CTL generated with MART-1(27-35) also lysed uncultured HLA-A2+ melanoma cells derived from tumor biopsies, indicating that this MART-1 epitope is likely to be expressed in association with HLA-A2 on the surface of tumor cells in vivo. CTL lines generated with MART-1(27-35) mediated 25- to 100-fold higher lytic activity than MART-1-reactive CTL grown from TIL in the presence of high dose IL-2. These results demonstrate that MART-1(27-35) peptide may represent an ideal candidate for Ag-specific immunotherapy in melanoma patients. PMID- 7868899 TI - Characterization of RFM mouse T lymphocyte anti-oncofetal antigen immunity in apparent tumor-free, long-term survivors of sublethal X-irradiation by limiting dilution T lymphocyte cloning. AB - Fractionated sublethal x-irradiation induces thymic lymphomas in up to 60% of RFM mice by 6 mo after irradiation, but no thymomas arise after 6 mo. All radiation induced tumors expressed oncofetal Ag (OFA) and thymic OFA expression significantly preceded detectable thymomas. To determine whether lymphoma-free, radiation survivor mice had anti-OFA T cell immunity, we analyzed their clonable 5T lymphoma-reactive T lymphocytes and determined the resistance of such mice to challenge with RFM lymphoma cells. RFM mice that were irradiated 6 to 6.5 mo earlier, but which had no apparent tumors, had no more resistance to OFA+ 5T lymphoma cell challenge than nonirradiated age-matched mice. These mice actually developed maximal tumor incidence significantly faster. Analyses of 5T lymphoma reactive T cell clones established from RFM mice 11 mo after irradiation, however, suggest that activation of anti-OFA immunity occurred subsequent to irradiation. Previously irradiated RFM mice yielded 257% more tumor-reactive T cell clones/mouse than non-irradiated controls. All clones from both sets of mice specifically proliferated to purified OFA. Each irradiated mouse yielded some clones that proliferated to fivefold lower doses of OFA than did any T cell clones from nonirradiated mice. Only these low-dose OFA-reactive clones responded equally to irradiated 4T and 5T cells by proliferation, IFN-gamma secretion, and target lymphoma cell killing. 4T cells express less OFA/cell than 5T cells. Some noncytotoxic CD8 T cells that inhibited cytotoxic T cell function were cloned only from irradiated RFM mice. PMID- 7868900 TI - Regulatory mechanisms for production of IFN-gamma and TNF by antitumor T cells or macrophages in the tumor-bearing state. AB - Spleen cells from BALB/c mice bearing a syngeneic tumor (CSA1 M) 2 to 3 wk after inoculation with CSA1 M cells produced IL-2, IFN-gamma, and TNF upon in vitro cultures. This was previously demonstrated to be a result of collaboration between tumor-primed CD4+ T cells and APCs binding CSA1 M tumor Ags in vivo. The IL-2- and IFN-gamma-producing capacities decreased with the progress of tumor bearing stages. This was parallel to the levels of IL-2 and IFN-gamma mRNAs expressed by cultured spleen cells. In contrast, comparable levels of TNF mRNA were expressed by all groups of cultured cells. However, large amounts of TNF were secreted by the cells from early but not from late tumor-bearing mice. TNF was produced mainly by the non-T cell fraction upon stimulation with CD4+ T cell derived IFN-gamma. Therefore, the reduced TNF production by whole spleen cells from late tumor-bearing mice was restored by addition of rIFN-gamma to their cultures. Reciprocally to the progressive decrease in the production of IFN gamma/TNF, the capacities of tumor-bearing mice to produce TGF-beta and IL-6 increased along with tumor growth. TGF-beta suppressed production of IL-2, IFN gamma, and TNF, but not of IL-6. Moreover, IFN-gamma/TNF production was negatively regulated by IL-6. Taken together with the fact that the growth of CSA1 M cells is completely inhibited by the combination of TNF and IFN-gamma, these results demonstrate that the tumor-bearing state induces an abnormal cytokine network under which the production of antitumor cytokines is negatively regulated. PMID- 7868901 TI - Mutation of residues in the C3dg region of human complement component C3 corresponding to a proposed binding site for complement receptor type 2 (CR2, CD21) does not abolish binding of iC3b or C3dg to CR2. AB - Most evidence points toward there being a shared binding site in complement receptor type 2 (CR2, CD21) for the complement ligand C3dg and the EBV surface envelope glycoprotein gp350/220. Indeed, synthetic peptide studies have suggested that the CR2-binding sites in human C3dg and EBV gp350/220 share a similar sequence motif. The proposed CR2-binding sequence in C3dg is EDPGKQLYNVEA (residues 1199-1210 of mature C3), whereas that in EBV gp350/220 is EDPGFFNVEI (residues identical to C3dg are underlined). To further examine the role of amino acids 1199-1210 in the binding of the C3 fragments iC3b and C3dg to CR2, the following alanine-substitution variants of human C3 were tested in two independent CR2-binding assays: ED1199,1200AA; KQ1203,1204AA; L1205A; Y1206A; NV1207,1208AA; E1209A; and ED-KQ-NV1199,1200-1203,1204-1207,1208AA-AA-AA. Also engineered and tested was a chimeric C3 molecule in which the 1199-1210 sequence (PVPGGYQLTLEA) from the non-CR2-binding trout C3 molecule was grafted onto a human C3 background. Recombinant C3 proteins were expressed transiently in COS-1 cells, deposited as C3b on C3 convertase-bearing sheep erythrocytes and finally converted to cell-bound iC3b or C3dg using factors H and I. Binding of EAC423bi and EAC423dg to CR2 on Raji cells or EAC423dg to soluble CR2 was assessed. In most cases, the substitutions had little effect on CR2-binding activity and even in the case of the most highly substituted variants, the decrease in CR2-binding activity was less than twofold. Thus, contrary to the results anticipated from synthetic peptide studies, the single and multiple substitutions to the C3 sequence tested failed to corroborate a role for the 1199-1210 sequence in the C3dg-CR2 interaction. PMID- 7868902 TI - Human IL-1 beta processing and secretion in recombinant baculovirus-infected Sf9 cells is blocked by the cowpox virus serpin crmA. AB - Biologically active, mature IL-1 beta (mIL-1 beta) is released from activated monocytes after proteolytic processing from an inactive precursor (pIL-1 beta). IL-1 beta converting enzyme (ICE), the first member of a newly discovered family of cysteine proteinases, is required for this processing event. The cleaved cytokine is released from monocytes by an unknown mechanism which does not employ a standard hydrophobic signal sequence. As in mammalian fibroblasts, insect Sf9 cells do not normally process or secrete human IL-1 beta. The expression of active ICE enables Sf9 cells to process 31-kDa pIL-1 beta correctly at Asp27 and Asp116, and to export 17.5-kDa mIL-1 beta. The recombinant heterodimeric human enzyme purified from Sf9 cells possesses a sp. act. of 2.9 +/- 0.5 x 10(6) U/mg and is indistinguishable from native ICE with regard to its subunit composition and catalytic properties. In this system, co-expression of the cowpox virus crmA gene, an extremely potent serpin inhibitor of ICE (Ki < 7 pM), inhibits ICE activation completely and blocks pIL-1 beta processing and mIL-1 beta secretion by approximately 95%. The results indicate that ICE, in addition to its processing function, facilitates the transport of IL-1 beta across the plasma membrane. PMID- 7868903 TI - Substrate specificities of the protease of mouse serum Ra-reactive factor. AB - Ra-reactive factor (RaRF) is a serum bactericidal factor whose function seems to be to activate C in a manner similar to that of C1, but with activation triggered by binding to bacterial polysaccharides instead of to immune complexes. It is composed of multiple polysaccharide-binding subunits associated with a novel serine protease, and its overall structural organization is similar to that of C1. This similarity extends to the serine protease component, which shares a similar modular construction and about 40% sequence identity with the C1r and C1s subcomponents of C1. In this study, we examined the substrate specificity of mouse RaRF by assaying its ability to cleave C components C3, C4, and C5, and its activity against the murine C4 isotype, sex-limited protein. Our results revealed that RaRF preferentially cleaves the C4 alpha-chain with specific activities 20- to 100-fold greater than either human or murine C1s, and that RaRF also cleaves the C3 alpha-chain, but with a lower efficiency than C4 alpha. We also found that RaRF is much less sensitive than C1s to mutations near the proteolytic site and that the two proteases show different reactivities against synthetic substrates. Hence, although the RaRF protease and C1s have similar structures and play similar roles in C activation, they also display clear differences in substrate range and in the details of their substrate recognition mechanisms. Finally, we found that RaRF does not cleave sex-limited protein even at a level 100-fold higher than necessary for C4 cleavage. PMID- 7868904 TI - IL-8 specifically binds to endothelial but not to smooth muscle cells. AB - The proinflammatory cytokine and potent chemoattractant IL-8 is involved in regulation of infectious or inflammatory processes. Human vascular endothelial cells (EC) and smooth muscle cells (SMC) probably contribute to these responses by recognition and/or production of rIL-8. We demonstrate here in competitive binding studies with radiolabeled rIL-8 that EC and fibroblasts, but not SMC, specifically bind IL-8 with low affinity. The binding was not saturated by ligand concentrations up to 80 nM 125I-rIL-8. Unlabeled neutrophil-activating peptide-2 competed the binding of 125I-rIL-8, although less potently than unlabeled rIL-8, as reported previously for polymorphonuclear neutrophils. In contrast, connective tissue-activating peptide III, platelet factor 4, or lysozyme did not reduce binding of 125I-rIL-8 to EC or fibroblasts. In accordance with these binding studies, EC and fibroblasts, but not SMC, expressed human IL-8 receptor type I mRNA. Neither cell type expressed mRNA for IL-8 receptor type II. Stimulation with IL-1 alpha or LPS did not alter the results obtained in PCR or binding studies. Although SMC did not express specific binding sites for IL-8, Western blot experiments showed that IL-1 alpha-, TNF-, or LPS-stimulated SMC released two major immunoreactive isoforms of IL-8 in a time- and dose-dependent manner. The m.w. were similar to IL-8 isoforms released by EC or mononuclear cells. The differential capacity of EC and SMC to produce IL-8 and express IL-8 binding sites indicates that vascular cell-derived IL-8 may contribute to differential regulation of infectious and inflammatory responses in the vessel wall. PMID- 7868905 TI - Isolation of nine gene sequences induced by silica in murine macrophages. AB - Macrophage activation by silica is the initial step in the development of silicosis. To identify genes that might be involved in silica-mediated activation, RAW 264.7 mouse macrophages were treated with silica for 48 h, and a subtracted cDNA library enriched for silica-induced genes (SIG) was constructed and differentially screened. Nine cDNA clones (designated SIG-12, -14, -20, -41, 61, -81, -91, -92, and -111) were partially sequenced and compared with sequences in GenBank/EMBL databases. SIG-12, -14, and -20 corresponded to the genes for ribosomal proteins L13a, L32, and L26, respectively. SIG-61 is the mouse homologue of p21 RhoC. SIG-91 is identical to the 67-kDa high-affinity laminin receptor. Four genes were not identified and are novel. All of the mRNAs corresponding to the nine cloned cDNAs were inducible by silica. Steady-state levels of mRNAs in RAW 264.7 cells treated with various macrophage activators and inducers of signal transduction pathways were determined. A complex pattern of induction and repression was found, indicating that upon phagocytosis of silica particles, many regulatory mechanisms of gene expression are simultaneously triggered. PMID- 7868906 TI - In vivo regulation of rat neutrophil apoptosis occurring spontaneously or induced with TNF-alpha or cycloheximide. AB - We previously demonstrated that human TNF-alpha induces rapid apoptosis of human neutrophils. To understand better the in vivo significance of neutrophil apoptosis, we examined spontaneous, recombinant human and mouse TNF-alpha- or cycloheximide-induced apoptosis of normal peripheral blood neutrophils (PBN), PBN from rats injected i.p. with proteose peptone or a streptococcus preparation, OK 432 (inflammatory PBN), peritoneally exudated neutrophils (PEN) obtained after a proteose peptone injection, and normal bone marrow neutrophils. The following observations were made. 1) Normal PBN responded to TNF-alpha, but PEN, normal bone marrow neutrophils, and inflammatory PBN at 12 h after stimulation did not. 2) The sensitivity to TNF-alpha of the inflammatory PBN started to decrease at 3 h, was lowest at 12 h, and was almost restored at 52 h after stimulation. 3) Spontaneous apoptosis of normal and inflammatory PBN reached 25% at 12 h after in vitro incubation, but that of PEN and normal bone marrow neutrophils was very low over this period. 4) The sensitivity to cycloheximide (6 h incubation) was high for normal PBN and bone marrow neutrophils, but low for PEN and inflammatory PBN after 12 h. 5) 125I-rhTNF-alpha binding of bone marrow neutrophils was significantly lower than that of normal and inflammatory PBN and PEN. 6) TNF alpha-induced apoptosis of normal or inflammatory PBN and bone marrow neutrophils was enhanced by treatment with low doses of cycloheximide that alone were barely able to induce neutrophil apoptosis; however, apoptosis of PEN was not. The mechanisms and in vivo significance of these phenomena are discussed. PMID- 7868907 TI - Investigation of neutrophil signal transduction using a specific inhibitor of phosphatidylinositol 3-kinase. AB - Neutrophils contain a multicomponent NADPH oxidase system that is involved in the production of microbicidal oxidants. Stimulation of human neutrophils with the peptide FMLP activates this respiratory burst enzyme to produce superoxide and also has been shown to result in activation of phosphatidylinositol (Ptdlns) 3 kinase. Treatment of human neutrophils with 2-(4-morpholinyl)-8-phenyl-4H-1 benzopyran-4-one (LY294002), a potent and specific inhibitor of Ptdlns 3-kinase, resulted in complete inhibition of Ptdlns 3-kinase activity as well as in inhibition of superoxide production in FMLP-treated neutrophils in suspension; FMLP-stimulated oxidant production in adherent cells was also abolished. Treatment of human neutrophils with PMA resulted in production of superoxide without activation of Ptdlns 3-kinase; LY294002 did not block superoxide production in neutrophils exposed to PMA. In addition, LY294002 did not inhibit cellfree NADPH oxidase activation, CD11b-dependent adhesion, actin polymerization in response to FMLP, or FMLP-induced calcium flux. These results suggest that the signal transduction pathway of the FMLP-receptor involves activation of Ptdlns 3 kinase, which is required for subsequent superoxide production induced by the chemotactic peptide. Furthermore, Ptdlns 3-kinase may be located directly upstream of protein kinase C or other protein kinases, which in turn activate the NADPH oxidase system. PMID- 7868908 TI - Glomerular binding activity in MRL lpr serum consists of antibodies that bind to a DNA/histone/type IV collagen complex. AB - To clarify the pathogenesis of lupus nephritis, we developed an assay that defines a glomerular binding activity (GBA) in both murine and human lupus sera highly correlated with nephritis. In the current study, we used a cross adsorption strategy to establish that the GBA in MRL lpr serum binds to the glomerular basement membrane (GBM). We subsequently observed that this binding to the GBM was competitively inhibited by either exogenous DNA or histone, abrogated by pretreatment of the GBM with DNAse, and restored after DNase treatment with DNA/histone in a synergistic fashion. GBM binding was also completely inhibited by pretreatment of GBM with collagenase but not heparatinase. The effect of collagenase was not reversed by the subsequent addition of DNA, but was restored by the sequential re-addition of type IV collagen and DNA. By using purified basement membrane components, we found that MRL lpr serum bound avidly to DNA coated on type I collagen but less well (or not at all) to DNA coated on type IV collagen, laminin, or fibronectin. Histone pretreatment of type IV collagen before DNA addition, however, synergistically enhanced binding in a fashion similar to that seen with native GBM. Thus, the GBA in MRL lpr serum seems to be comprised of autoantibodies that bind to histones and/or DNA that adhere to type IV collagen within the GBM. These data support the planted Ag hypothesis as the principal pathogenic mechanism in lupus nephritis and suggest that multiple autoantibodies may contribute to this disorder. PMID- 7868909 TI - Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. A novel mechanism of chronic intestinal inflammation. AB - The etiology and pathogenesis of inflammatory bowel disease (IBD) are unknown. Increasing evidence supports the theory that chronic IBD is the result of dysfunctional immunoregulation manifested by an inappropriate production of mucosal cytokines. The aim of the present study was to test the hypothesis that a specific mucosal imbalance of IL-1 and IL-1 receptor antagonist (IL-1ra) production plays an important role in the perpetuation and chronicity of intestinal inflammation. Total IL-1, IL-1ra, and the IL-1ra/IL-1 ratio were measured in freshly isolated intestinal mucosal cells, as well as in mucosal biopsies obtained from control, Crohn's disease, and ulcerative colitis patients. IL-1 alpha, IL-1 beta, and IL-1 ra were measured by specific non-cross-reacting radioimmunoassays and ELISA. A markedly significant decrease in the intestinal mucosal IL-1ra/IL-1 ratio was found in both Crohn's disease and ulcerative colitis patients when compared with control subjects (p < 0.01). The IL-1ra/IL-1 ratio correlated closely with the clinical severity of disease (r = -0.7846, p < 0.001). Furthermore, the observed decrease in the IL-1ra/IL-1 ratio was specific for IBD because a decreased IL-1ra/IL-1 ratio was not found in patients with self limiting colitis. These results support the hypothesis that an imbalance between IL-1 and IL-1ra production is of pathogenic importance in chronic inflammatory diseases, including IBD. PMID- 7868910 TI - Analysis of the New Zealand Black contribution to lupus-like renal disease. Multiple genes that operate in a threshold manner. AB - F1 progeny of New Zealand Black (NZB) and New Zealand White (NZW) mice spontaneously develop an autoimmune process remarkably similar to human systemic lupus erythematosus. Previous studies have implicated major genetic contributions from the NZW MHC and from a dominant NZB gene on chromosome 4. To identify additional NZB contributions to lupus-like disease, (NZB x SM/J)F1 x NZW backcross mice were followed for the development of severe renal disease and were comprehensively genotyped. Despite a 50% incidence of disease, significant associations between the presence of the NZB genotype and disease were noted on chromosomes 1, 4, 7, 10, 13, and 19. The data indicated that multiple NZB genes, in different combinations, contribute to severe renal disease, and that no single gene is required. To further investigate this NZB contribution, NZB x SM/J (NXSM) recombinant inbred (RI) strains were crossed with NZW mice, and F1 progeny were analyzed for the presence of lupus-like renal disease. Interestingly, nearly all of the (RI x NZW)F1 cohorts studied expressed some level of disease. Five RI strains generated a high incidence of disease, similar to (NZB x NZW)F1 mice, and nearly one-half of the cohorts developed disease at intermediate levels. Only two cohorts demonstrated very little disease, supporting the conclusion that multiple genes are capable of disease induction. Experiments correlating the genotypes of these RI strains with their ability to generate disease revealed that none of the disease-associated loci defined by the backcross analysis were present in all five RI strains that generated disease at high levels. Overall, both the backcross data and RI analysis provide additional support for the genetic complexity of lupus nephritis and uphold the conclusion that heterogeneous combinations of contributing NZB genes seem to operate in a threshold manner to generate the disease phenotype. PMID- 7868911 TI - HIV replication in IL-2-stimulated peripheral blood mononuclear cells is driven in an autocrine/paracrine manner by endogenous cytokines. AB - Replication of HIV is regulated by virus-encoded regulatory proteins, as well as by a variety of cellular factors including cytokines. In the present study, we have investigated the autocrine/paracrine effects of endogenous cytokines on HIV replication in primary PBMCs of healthy HIV seronegative individuals. Addition of rIL-2 to cultures between 0 and 72 h after isolation of PBMCs allowed the replication of primary HIV isolates and laboratory-adapted HIV strains to levels comparable with or greater than those obtained in parallel cultures of autologous PHA-blasts. In this regard, both major cellular targets of HIV infection, CD4+ T lymphocytes and mononuclear phagocytes, were maintained for several weeks in IL-2 stimulated PBMC cultures and virion production was observed in both cell lineages. The kinetics of secretion of several cytokines (such as TNF-alpha, IL-1 beta, IL-6, and IFN-gamma), as well as expression of cellular activation markers, paralleled HIV replication in IL-2-stimulated PBMCs. Endogenous pro-inflammatory cytokines and IFN-gamma played a major role in the regulation of HIV replication in IL-2-stimulated PBMCs, as determined by the ability of several anti-cytokine Abs or antagonists to suppress HIV production; this was not the case in parallel cultures of autologous PHA-blasts. Thus, IL-2-stimulated PBMCs may represent a more physiologic in vitro system than PHA-blasts for the study of HIV infection and replication, and should prove useful in investigating the role of cytokines and other host factors in the regulation of HIV production. PMID- 7868912 TI - A monoclonal autoantibody that promotes central nervous system remyelination in a model of multiple sclerosis is a natural autoantibody encoded by germline immunoglobulin genes. AB - Antibodies directed against self-Ags are frequently considered detrimental, and have been shown to play a pathogenic role in certain autoimmune diseases. However, the presence of autoreactive Abs in normal individuals suggests that some autoantibodies could participate in normal physiology. Our previous studies demonstrated that monoclonal autoantibodies SCH94.03 and SCH94.32, generated from the splenocytes of uninfected SJL/J mice injected with normal homogenized spinal cord, promote central nervous system remyelination when passively transferred into syngeneic mice chronically infected with Theiler's murine encephalomyelitis virus, an established experimental model of multiple sclerosis. In this study we show that these two monoclonal autoantibodies are identical, and have phenotypic characteristics of natural autoantibodies. By using a solid phase assay system, SCH94.03 and SCH94.32 showed reactivity toward several protein Ags and chemical haptens, with prominent reactivity toward spectrin, (4-hydroxy-3 nitrophenyl)acetyl, and fluorescein. Sequence analysis showed that both SCH94.03 and SCH94.32 were encoded by identical germline Ig light chain V kappa 10/J kappa 1 and heavy chain V23/DFL16.1/JH2 genes, with no definitive somatic mutations. These results indicate that a natural autoantibody participates in a beneficial physiologic response to central nervous system injury. PMID- 7868913 TI - Intragraft expression of cytokine transcripts during pig proislet xenograft rejection and tolerance in mice. AB - The rejection of pig proislet (islet precursor) xenografts in CBA/H mice is a CD4+ T cell-dependent process. The molecular mechanisms of xenograft rejection, xenograft survival during anti-CD4 mAb therapy and xenograft tolerance post withdrawal of anti-CD4 mAb administration, were examined by using a semiquantitative PCR method. Temporal analysis of intragraft cytokine mRNA demonstrated a Th0-like pattern of expression (IL-2, IFN-gamma, IL-3, IL-4, IL-5, and IL-10) on day 4 of the acute xenograft rejection process. From day 5, however, only Th2-associated transcripts (IL-3, IL-4, IL-5, and IL-10) were enhanced in xenografts compared with isograft controls. Immunohistochemistry showed that the principal participants in the rejection infiltrate were CD4+ T cells and eosinophils, with smaller numbers of CD8+ T cells. In vivo depletion of CD4+ T cells prevented xenograft rejection but had minimal effect on the peak levels of IL-2, IFN-gamma, and IL-10 mRNA; in contrast, the enhanced expression of IL-3, IL-4, and IL-5 transcripts seen in rejecting xenografts was abrogated. This established a positive correlation between acute xenograft rejection, presence of CD4+ T cells, and enhanced intragraft expression of mRNA for the Th2 type cytokines IL-3, IL-4, and IL-5. In tolerant hosts, long-term proislet xenograft survival and function (> 190 days) was accompanied by intragraft expression of IL-2 and IL-10 mRNA; IFN-gamma, IL-3, IL-4, and IL-5 mRNA were either undetected or not enhanced. The induced rejection of long-term functioning xenografts (> 170 days) in nontolerant hosts resulted in selective enhancement of IL-4 transcript expression. This study suggests that Th2-like CD4+ T cells are differentially activated in response to xenoantigen and that xenograft tolerance is associated with lack of expression of the Th2 cytokine, IL-4. PMID- 7868914 TI - IgG but not other classes of anti-[(H2A-H2B)-DNA] is an early sign of procainamide-induced lupus. AB - A longitudinal study was undertaken to characterize the autoantibodies induced during the course of procainamide treatment and to relate this information to the appearance of symptomatic drug-induced lupus. IgG, IgA, and IgM Abs to histones, native and denatured DNA, chromatin, and (H2A-H2B)-DNA were determined by ELISA in serial serum samples obtained over the course of an average of 2.1 yr on 22 patients undergoing treatment with procainamide and on an additional 9 patients after discontinuation of procainamide because of drug-induced lupus. Ten patients in the prospective group developed lupus-like symptoms after an average of 1.8 +/ 2.1 yr of procainamide treatment. Of the total of 19 patients with drug-induced lupus, 16 had IgG Abs to the (H2A-H2B)-DNA complex at the time of diagnosis; this autoantibody was first detected 0.9 +/- 1.3 yr before diagnosis in 7 patients. In contrast, the 9 patients who remained asymptomatic during treatment with procainamide for an average of 4.3 +/- 2.2 yr had negligible levels of IgG anti [(H2A-H2B)-DNA], although IgA and IgM Abs of this specificity were not uncommon. Abs to denatured DNA and histones were elicited coordinately, but these specificities did not discriminate symptomatic from asymptomatic procainamide treated patients. We conclude that chronic exposure to procainamide commonly elicited autoantibodies with specificities for denatured epitopes on DNA and histones and for native regions on the (H2A-H2B)-DNA subunit of chromatin. However, rapid switch to the IgG class of anti-[(H2A-H2B)-DNA] occurred only in patients who went on to develop symptomatic disease. PMID- 7868915 TI - Beta-cell-cytotoxic CD8+ T cells from nonobese diabetic mice use highly homologous T cell receptor alpha-chain CDR3 sequences. AB - Insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice results from a cell-mediated autoimmune process against pancreatic beta-cells. We have shown that beta-cell-cytotoxic CD8+ T cell clones can transfer IDDM to irradiated NOD mice if co-injected with nondiabetogenic CD4+ spleen T cells. To determine whether CTLs recruited to pancreatic islets recognize a restricted set of local Ags, we sequenced TCR-alpha and TCR-beta cDNA generated by anchor PCR from CD8+ CTL lines and clones derived from islets of 10 different NOD mice. These CTL lines were oligoclonal, but did not show skewed V alpha, V beta, J alpha, or J beta gene usage when compared with CD8+ spleen T cells. However, of the 26 different CTL-derived TCR-alpha sequences from all of these CTL lines and clones, 17 (65%) used one of three highly related, N region-encoded, CDR3 motifs. Motifs 1 and 2 (7 clonotypes each) contained a hydrophobic amino acid followed by Arg and a negatively charged or a polar residue (Asn or Gly), respectively. Motif 3 (3 clonotypes) was x-Arg-Gly. In 12 of these 17 rearrangements, the core sequence was followed by Tyr or Ser. By contrast, none of 31 different TCR-alpha rearrangements used by CD8+ spleen T cells encoded motifs 1 or 2, and only one encoded motif 3. Different TCR-beta rearrangements within individual lines also used homologous CDR3 sequences, but these sequences varied between lines. Skewed TCR-alpha-CDR3 usage by islet-derived CTLs was substantiated further by isolation of CTL clones transcribing highly homologous TCR-alpha, but different TCR-beta, rearrangements. These data suggest that CTLs recruited to pancreatic islets during spontaneous IDDM recognize a restricted set of beta-cell autoantigenic determinants. PMID- 7868916 TI - Breaking tolerance leads to autoantibody production but not autoimmune liver disease in hepatitis B virus envelope transgenic mice. AB - Hepatitis B virus (HBV) transgenic mice containing the HBV envelope open reading frame under the transcriptional control of the mouse albumin promoter express hepatitis B surface Ag (HBsAg) in all of their hepatocytes and secrete HBsAg (10 to 40 ng/ml) into the circulation. Because these transgenic mice show no signs of spontaneous liver cell injury or autoimmunity toward the viral (self-) Ag, we asked whether the state of self-tolerance could be reversed by the induction of an acute necroinflammatory liver disease or by immunization with HBV envelope proteins, with the aim of creating a transgenic model for chronic, immune mediated hepatitis. Our studies indicate that repetitive administration of bacterial LPS, IFN-gamma, or HBsAg-specific CTL, all of which were previously shown to cause liver cell injury and inflammation, does not break tolerance at the T or B cell level, suggesting that the intrahepatic lymphomononuclear cell infiltrate induced by these agents consists of HBsAg-nonspecific cells. The adoptive transfer of HBsAg-primed nontransgenic CD4+ T cells into transgenic mice did not induce anti-HBs autoantibody production by transgenic B cells, even though transgenic B cells were fully responsive to immunization with HBsAg when appropriate T cell help was provided in a nontransgenic environment. Immunization of transgenic mice with purified HBsAg in CFA and repetitive infection with rHBV envelope vaccinia virus led to production of T cell-dependent anti-HBs autoantibodies that cleared HBsAg from the serum, but not to activation of HBsAg specific CTL. We conclude that HBV envelope transgenic mice are largely tolerant to the transgene product at the T cell but not at the B cell level, and that the activation of an anti-HBs response was not sufficient to induce an autoimmune liver disease in this HBV envelope transgenic mouse model. PMID- 7868917 TI - Flow cytometry detection of surface antigens on fresh, unfixed red blood cells infected by Plasmodium falciparum. AB - The immunofluorescence detection of parasite-specific antigens on the surface of red blood cells infected by Plasmodium falciparum parasites is usually performed by visual detection under a fluorescence microscope. We describe here a technique permitting the analysis of surface immunofluorescence labelling by flow cytometry. Infected red blood cells are selected on the basis of their parasitic DNA and RNA content by Hoechst and Thiazole Orange vital dyes. Cytometric analysis of these labels, as well as general erythrocyte characteristics assessed by analysis of forward and side scatter allows the selection of viable intact infected erythrocytes from other blood cells. The integrity of these selected erythrocytes was confirmed by the absence of labelling with antibodies directed against internal components such as spectrin. This technique permits the detection of specific surface immunofluorescence staining on red blood cells infected with mature stages of P. falciparum by antibodies in sera from hyperimmune Saimiri monkeys. Using Thiazole Orange dye for detection of parasitised cells, this analysis was performed on a FACSscan apparatus equipped with a single laser. PMID- 7868918 TI - Purification of bacterially expressed single chain Fv antibodies for clinical applications using metal chelate chromatography. AB - A new procedure is described for the purification of an anti-carcinoembryonic antigen (CEA) single chain Fv (scFv), referred to as MFE-23, from bacterial supernatant. A simple insertion of a hexa-histidine tail fused at the C-terminus (MFE-23 His) provides an affinity tag which selectively binds to transition metal ions immobilised on an iminodiacetic acid (IDA) derivitised solid phase matrix. This method proved to be superior to standard CEA antigen affinity chromatography in the following ways. (1) A higher yield was produced (10 mg/l as opposed to 2.2 mg/l of bacterial supernatant). The latter figure was largely affected by the limited availability (size of the column) of immobilised CEA antigen. (2) Scale up was relatively simple and less costly. (3) The risk of tumour derived antigen leaching from the column is eliminated. Results showed that immobilised Cu2+ ions were more effective than Ni2+ and Zn2+ ions in retaining the His tagged product giving a 90% pure product on elution. Clinical grade material was generated using size exclusion chromatography to remove aggregated material, and Detoxi gel to remove bacterial endotoxins. Validation assays to measure DNA, copper and endotoxins were performed to assess the levels of contaminants. MFE-23 His retained 84% antigen binding after 6 months storage at 4 degrees C and > 75% after radiolabelling. Further experiments confirmed that the His tail did not affect biodistribution and tumour localisation in nude mice bearing human colorectal tumour xenografts. PMID- 7868919 TI - The international standard for granulocyte-macrophage colony stimulating factor (GM-CSF). Evaluation in an international collaborative study. Participants of the Collaborative Study. AB - Two ampouled preparations of granulocyte-macrophage colony stimulating factor (GM CSF) have been evaluated by twenty nine laboratories in eleven countries for their suitability to serve as international standards for these materials. The preparations were assayed in a wide range of in vitro bioassays and immunoassays. On the basis of results reported here, with the agreement of the participants in the study and with the authorisation of the Expert Committee on Biological Standardization (ECBS) of the World Health Organization (WHO) one of the preparations (88/646) was established as the international standard for GM-CSF. PMID- 7868921 TI - PEPMOTIF: a program for locating class I major histocompatibility complex restricted peptides in protein sequences. AB - PEPMOTIF is a computer program which analyzes protein sequences for the occurrence of peptides up to ten residues in length which contain motifs presented by particular class I major histocompatibility complexes. Any peptide motifs defined by the user can be identified in a protein sequence of interest. PEPMOTIF generates a listing of all motif-containing peptides found in the protein, and two modes of data output are provided: (1) direct printout, or (2) storage in a text file on disk. PMID- 7868920 TI - In vitro production of monoclonal antibodies in high concentration in a new and easy to handle modular minifermenter. AB - This paper describes a new and easy to handle reusable minifermenter for high density culture of hybridoma and other cells. The culture apparatus is composed of two modules: a 40 ml disposable cell culture and antibody production chamber (the 'production module') and a 550 ml medium reservoir (the 'supply module'). The two modules are separated from each other by a dialysis membrane allowing passage of low molecular mass nutrients and metabolites. The monoclonal antibodies are produced and enriched in the production module. The outer part of this module is made from a thin gas-permeable silicone rubber membrane allowing exchange of gases (oxygen and carbon dioxide). To start the culture, the cells are injected into the production module through ports in the silicone rubber which are equipped with Luer Lock connectors. Samples can be removed in the same way. For culturing, the minifermenter is rolled on a roller apparatus in a carbon dioxide-supplied incubator. Depending on the individual properties of the hybridoma cells cultured, cell densities of more than 10 x 10(6) (in some cases up to 35 x 10(6)) cells per ml and monoclonal antibody concentrations of several mg per ml can be obtained in the new minifermenter. On average, 61 mg (range: 9 159 mg) could be produced within 1-4 weeks. In terms of their properties the monoclonal antibodies produced in the new modular minifermenter were indistinguishable from antibodies prepared from ascitic fluid or from the supernatant of conventional stationary culture. The culture method is a useful alternative to the in vivo production method in mice. In addition, it represents a completely new, inexpensive and easy to handle general solution to the problem of culturing cells in high density and obtaining cellular products in high concentrations. PMID- 7868922 TI - Conventional immunoassays underestimate anti-GST antibody titre. AB - This paper highlights problems associated with the quantitation of serum antibody levels to recombinant glutathione S-transferase (GST). Measurement of anti-GST antibodies in conventional immunoassays, where GST is bound directly to the ELISA plate, was found to substantially underestimate the amount of GST-specific antibody levels in test sera. This insensitivity in immunoassay of anti-GST antibodies can be overcome by using any one of several recombinant GST fusion proteins as the coating antigen in ELISA rather than simply GST. Comparison of anti-GST antibody titres assessed by the two procedures indicated that use of unfused GST underestimated the anti-GST antibody titre by more than ten-fold. PMID- 7868923 TI - Organ culture of human lymphoid tissue. I. Characteristics of the system. AB - The major aim of three-dimensional tissue culture is to preserve the natural architecture of the tissue and thereby allow the cells to retain their original functions during in vitro cultivation. Here we describe a method for the rapid preparation of three-dimensional tissue explants from human lymphoid organs. The precision-cut tissue slices are of uniform size and thickness and can be cryopreserved and stored in liquid nitrogen without substantial loss of viability or functionality of the cells. Upon in vitro culture, cells within the explants survived as well as their counterparts cultured in single cell suspension. However, spontaneous immunoglobulin (Ig) production in explants started more promptly and often reached considerably higher levels than that in suspension cultures run in parallel. Lymphocytes within the slices could be activated by polyclonal stimuli such as PHA, as shown by the upregulation of the activation markers CD23 and CD25 on B and T cells, respectively. However, approximately five fold higher concentrations of mitogen than those used for suspension cultures were needed. Taken together, the system presented here constitutes a potent tool for the investigation of the complex interactions leading to activation and differentiation of B and T cells in lymphoid organs. PMID- 7868924 TI - An enzyme immunoassay for the determination of anti-IgA antibodies using polyclonal human IgA. AB - An enzyme immunoassay (EIA) for screening and quantitation of serum anti-IgA antibodies of IgG class is described. This method is based on the use of purified polyclonal human serum IgA as the coating antigen and a commercial alkaline phosphatase-conjugated anti-human IgG as the detecting antibody. Nonspecific reactions were minimized by blocking vacant protein binding sites with bovine serum albumin and by using individual sample blanks. The IgA specificity of a positive antibody finding was confirmed by testing inhibition: pooled normal human serum inhibited the binding of specific antibodies by over 80%. The same degree of inhibition could also be demonstrated by a commercial myeloma IgA preparation and by the IgA used for coating but not by IgA-deficient serum (< 0.05 mg/l). On the basis of the mean anti-IgA antibody titre in EIA, a value of 12,000 arbitrary units of anti-IgA per litre (AU/l) was assigned to a patient serum used as standard in the assay. Anti-IgA results obtained by EIA and haemagglutination correlated well, which makes it possible to compare earlier HA results with those obtained now by EIA. The measuring range of the assay was 0.6 27 AU/l and the lowest quantifiable concentration 7 AU/l. The dilution requirement for serum was 1/16. The interassay coefficients of variation for control sera with antibody levels from 35 AU/l to 3770 AU/l varied from 9 to 12%. PMID- 7868925 TI - Recruitment of alloreactive natural killer cells to the rat peritoneum by a transfected cell line secreting rat recombinant interleukin-2. AB - In order to obtain large numbers of natural killer (NK) cells from single rats for functional studies, we have devised a method for the generation of IL-2 activated NK cells in vivo. Rats were implanted intraperitoneally with cell impermeable diffusion chambers (DC) containing cultures of transfected Chinese hamster ovary (CHO) cells secreting rat recombinant interleukin-2 (rIL-2). This resulted in a dramatic increase in the peritoneal exudate cell (PEC) number with a peak (300-1000 x 10(6)) 1 week after implantation. The majority were mononuclear cells of which a large proportion were CD3-NKR-P1+ NK cells, but with substantial numbers of macrophages (M phi) and CD3+8+NKR-P1+ T cells also. The NK activity against standard tumor target cells was high among PEC from six different inbred rat strains tested. However, the NK cell-mediated reactivity against concanavalin A (ConA)-activated T cell blasts from a panel of major histocompatibility complex (MHC) congenic strains differed widely. PEC from some strains (PVG, LOU/C, and AO) efficiently lysed all the MHC-disparate lymphoblasts. In other strains (BN and LEW) more restricted allorecognition repertoires were observed, whereas PEC from one strain (DA) were unresponsive. The secretion of rat rIL-2 intraperitoneally did not lead to a significant increase in the IL-2 level in the blood or in the total number or activity of NK cells in blood and spleen. The present method represents a most potent technique for generating large numbers of functional rat NK cells and shows the high efficiency with which IL-2 can induce NK cell recruitment in vivo. PMID- 7868926 TI - Establishment of a single-step hybridoma cloning protocol using an automated cell transfer system: comparison with limiting dilution. AB - An easy-to-standardize single-step protocol of hybridoma cloning has been established using a recently introduced, commercially available cell transfer system. By controlling the volume of air within a sealed glass micropipette by means of a Peltier device, single cells are gently collected or ejected. The transfer of cells from a source dish to the wells of a target microplate is controlled by a microprocessor. Since collection as well as expulsion of cells is done under microscopic control seeding of single cells can be guaranteed. Monoclonality is therefore reproducibly achieved in a single step, reducing the time required for cloning enormously, and conserving man-power and material. Since the automated transfer of cells is time-saving and easy-to-standardize, it substantially facilitates cloning of hybridoma. The present protocol therefore represents an alternative to limiting-dilution cloning as well as to other previously introduced techniques of single-cell cloning. It is easily adapted to a wide spectrum of other cell types and can therefore be used in many other applications involving single cell manipulation. PMID- 7868927 TI - IgA, IgG and IgM quantification in bronchoalveolar lavage fluids from allergic rhinitics, allergic asthmatics, and normal subjects by monoclonal antibody-based immunoenzymetric assays. AB - Recent reports have suggested that human secretory IgA (sIgA) may have a role in the mediation of atopic disease. We have studied the levels of sIgA, IgA, IgG and IgM in bronchoalveolar lavage (BAL) fluids collected from lungs of healthy non allergic adults (n = 14), allergic subjects with rhinitis (n = 15), and allergic asthmatics (n = 13), using a panel of monoclonal antibody-based immunoenzymetric assays (IEMAs). In contrast to commercially available immunodiffusion and nephelometric assays, these IEMAs employ highly specific monoclonal antibodies and demonstrate required precision (intra-assay CVs < 17%), parallelism (inter dilutional CVs < 20%) at minimal detectable immunoglobulin levels in the ng/ml range, and excellent specificity with < 0.1% crossreactivity for heterologous immunoglobulin isotypes. Using these assays, we have observed a significant correlation between sIgA levels and total IgA levels in BAL fluids from all the study patients (r = 0.94; p < 0.01). The percentage of sIgA to total IgA was 84.0 +/- 2.2%. sIgA in BAL fluids from allergic rhinitics (18.0 +/- 2.5 micrograms/ml) and allergic asthmatics (15.5 +/- 2.5 micrograms/ml) were higher than those from nonallergic subjects (10.2 +/- 1.9 micrograms/ml). The only statistically significant difference in sIgA levels was observed in BAL fluids from the rhinitics and nonallergic groups (p = 0.03). Similar differences among the groups were found for levels of total IgA in BAL fluid. There were no significant differences in the levels of IgM and IgG in BAL fluids among the three groups of subjects. We conclude from these results that IgA is the predominant immunoglobulin on the airway surface and that it appears to be produced locally. PMID- 7868928 TI - A method to trap IgG antibodies within functional membrane vesicles. AB - Monoclonal antibodies have been used extensively to study the roles of specific extracellular proteins in cellular activation. Due to the large size of these molecules, their use for the study of receptor-mediated activation of intracellular processes has been limited. This report describes a method to introduce whole IgG antibody molecules into large functional membrane vesicles (ghosts) derived from rat basophilic leukemia (RBL) cells. Furthermore, an IgG1 mouse monoclonal antibody (JRK) directed against the cytoplasmic portion of the beta subunit of the high affinity receptor for IgE (Fc epsilon RI) can partially inhibit Fc epsilon RI-mediated PI hydrolysis through modest effects on both basal and receptor-mediated activation of phospholipase C. PMID- 7868929 TI - Microculture tetrazolium assays: a comparison between two new tetrazolium salts, XTT and MTS. AB - Microculture tetrazolium assays are being widely exploited to investigate the mechanisms of both cell activation and cell damage. They are colorimetric assays which are based upon the bioreduction of a tetrazolium salt to an intensely coloured formazan. We contrast the responses obtainable with two new tetrazolium salts, MTS and XTT, when used on the rat lymphoma cell line (Nb2 cells), which has been activated by human growth hormone. These tetrazolium salts, unlike the more commonly used MTT, form soluble formazans upon bioreduction by the activated cells. This has the advantage that it eliminates the error-prone solubilisation step which is required for the microculture tetrazolium assays which employ MTT. Bioreduction of XTT and MTS usually requires addition of an intermediate electron acceptor, phenazine methosulphate (PMS). We found that the XTT/PMS, but not the MTS/PMS, reagent mixture was unstable. Nucleation and crystal formation in the XTT/PMS reagent mixture, prepared in DPBS, could occur within 1-3 min. This resulted in a decline in XTT-formazan production and manifested itself in the microculture tetrazolium assay as both poor within-assay precision and serious assay drift. Several features of the system suggested that the formation of charge-transfer complexes between XTT and PMS accounted for this instability. No such instability was encountered when MTS and PMS were mixed. We demonstrate that MTS/PMS provides microculture tetrazolium assays for hGH which are free from these serious artefacts and which are uniquely precise. In conclusion we therefore advocate the use of MTS in preference to XTT for the new generation of microculture tetrazolium assays. PMID- 7868930 TI - [CD4 TIL (Tumor Infiltrating Lymphocytes) induce complete response in patients treated with IL-2 (Interleukin-2). Preliminary study]. AB - This study analyzed clinical response induced by TIL in patients with renal cell carcinoma previously treated by interleukin-2. Six patients (4 men, 2 women, mean age 44.3 years) with measurable metastatic localizations have been treated by TIL reinjection (0.02 to 7.6 x 10(10) cells). TIL phenotype was a combination of CD4 and CD8 in 3 patients, predominantly CD4 in two patients and predominantly CD8 in one patient. Previous treatment by interleukin-2 induced one partial response, 2 stabilizations of the disease and 3 tumoral progressions. TIL led to an amelioration for 4 patients: 2 were in complete response, 2 were stabilized and 2 had tumoral progression and decreased. This study shows that CD4 TIL may improve an initially response induced by IL-2 therapy. PMID- 7868931 TI - [Circumstances of the detection of kidney cancer. Current part of accidental discoveries]. AB - Kidney cancer accounts for 3% of all cancers, with approximately 85% of tumors arising in the renal parenchyma (renal cell carcinoma). To evaluate the part of the incidental detection of the renal carcinoma, we performed a retrospective review of the 302 patients treated for this reason in our department between April 1981 and October 1992. For the purpose of a historical comparison, 2 periods of 6 years were compared: 1981-1986 and 1987-1992. During 1981 to 1992, 71 patients (25.8%) were totally asymptomatic, with a significant improvement of the incidentally detected tumors from 1981-1986 (15%) to 1987-1992 (33.7%) (p < 0.001). Renal ultrasonography, which is responsible for 97% of the incidental diagnosis, allow for a better detection in the right kidney (60.3% vs. 39.7% in the left kidney) (p < 0.05). Primary tumor size and clinical stage (with Robson or the TNM 1992 classification) were significantly smaller (47.3 +/- 19.9 mm for the asymptomatic group vs. 71.6 +/- 34.1 mm for the symptomatic tumors) and lower respectively, in the asymptomatic group than in the symptomatic group (p < 0.001). The five-year survival rate (actuarial method) of the incidental cases tended to the better for the asymptomatic cases (87.5% vs. 39% for the symptomatic tumors) (p < 0.05). Most of the authors agree that incidental diagnosis has led to lower tumor size and stage and possibly better survival rate compared to cases where the diagnosis was suspected clinically. However, prospective studies on a large scale are needed to evaluate the role of nephron sparing surgery for incidental cancer of the kidney. Nowadays, the treatment remains radical nephectomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868932 TI - [Nephroblastoma at the hospital unit in Abidjan. Apropos of 60 cases]. AB - A series of 60 cases of nephroblastoma treated at the Abidjan University Hospital from 1971 to 1981 were reported. Nephroblastoma is a frequent childhood tumour representing 26.40% of malignant childhood tumours. It is a tumour of the young child. There is no sex predominance and both sides are equally involved. The tumour is the only clinical manifestation and is always palapable. Factors of poor prognosis were often observed in our patients including: age less than 2 years with major tumour volume (56.6%), advanced stage (89.3%). Antimitotic treatment was used in all cases and in 16 surgery was required. The poor prognosis criteria observed in this series explain the poor outcome in most of the cases. PMID- 7868933 TI - [Ureteral stent reinforced with a spiral--an alternative to internal drainage of urine]. AB - Internal urinary diversion of chronic ureteral obstruction is not sufficient in up to 60% of the cases. Factors for this high failure rate are tumor compression, catheter kinking or a small stent lumen. To prevent such problems we have developed a new ureteral stent which is stable in form in spite of a large stent lumen. This catheter is made of a thin polyurethane tube which is supported by a built-in metallic spiral wire. We have used this stent in 16 cases of chronic ureteral obstruction. Stent placement was successful in 14 cases. Other than urinary tract infection in two cases, bladder urgency in one case and stent dislocation in another case there were no complications. Hydronephrosis disappeared soon after stent application in 12 out of 14 cases. In the remaining two cases hydronephrosis was decreased, but not totally eliminated. Catheters were left in place for an average of 6.5 weeks (2.5-8.5). A change of catheter due to catheter blockage was necessary only in one case. In conclusion, this spiral reinforced stent enables a better internal urinary drainage especially in cases of malignant ureteral obstruction. PMID- 7868934 TI - [Surgical correction of recurrent uterine prolapse by means of the PTFE (1) plate]. AB - Surgical cure of recurrent prolapsus of the genital organs or after hysterectomy is not an easy to attain. Most authors use prosthetic to obtain a satisfactory anatomic and functional results which lasts. Since 1985, the tissue-reinforcement prosthesis GORE-TEX* was used in this type of situation for 50 patients. The operation remains simple, but certain technical details are of great importance. The material is solid and well tolerated. Results are good with long follow-up. One of the important points for a successful treatment is probably to treat directly and simultaneously all the lesions involved, recognizing that prolapsus of the genital organs is a continuous disease process. PMID- 7868935 TI - [Carcinosarcoma of the bladder. Apropos of two cases]. AB - The authors report two cases of carcinosarcoma of the bladder, review the literature, and study the clinical, histological, therapeutic and evolutive aspects of this unusual tumor. It is a rare tumor which represent less than 0.5 per cent of all cancers of the bladder. It is three times more frequent in men than in women. Hematuria is the most frequent alarming symptom and pathogenesis is still a matter of debate. Diagnosis is based on the pathological examination including immunohistochemical study and, if necessary, with electron microscopy examination. The tumor contains two highly malignant cellular components: one is epithelial and the other is mesenchymal. Treatment is not well codified. Early diagnosis and radical cystectomy seem to improve the prognosis, which is usually poor. 5 year survival rate is about 20 per cent. PMID- 7868936 TI - [Legal aspects of repair of traumatic injuries of the posterior urethra in men]. AB - When a urologist is required to treat a traumatic rupture of the posterior urethra in a man, he must evaluate the potential urinary and sexual sequelae, in order to be able to address specific questions raised by the injured man and also by experts appointed by the court and the insurance. The aim of this study was to review the elements of bodily damages estimation. Medico-legal aspects of urethral traumatism are underlined. The urologist must be able to establish the basis for compensation of bodily damages and the expenses entailed by further treatments required by the sequelae of the uro-genital lesions. The basis for a pretium doloris, sexual and eventually juvenile damages should also be indicated in any certificate given to the patient or to the court experts. PMID- 7868937 TI - [Blind duplication of the ureter. Apropos of a case]. AB - The authors report on a case of a 24 year-old man with a double-blind duplication of the ureter, which was diagnosed in the workup of a microscopic hematuria. The patient who had no symptoms and a normal renal function has been followed up at regular intervals. The diagnosis of this malformation is difficult as long as it is asymptomatic and does not affect the excretory function. PMID- 7868938 TI - Modern surgical treatment of pancreatic cancer. PMID- 7868939 TI - The islet-acinar axis of the pancreas. PMID- 7868940 TI - Combination treatment of nitrosamine-induced pancreatic cancers in hamsters with analogs of LH-RH and a bombesin/GRP antagonist. AB - Analogs of luteinizing hormone-releasing hormone (LH-RH) and bombesin/gastrin releasing peptide were previously shown to inhibit the growth of experimental pancreatic cancers. In the present study, in an attempt to increase the efficacy of therapy, female Syrian golden hamsters with N-nitrosobis(2-oxopropyl)amine induced pancreatic cancers were treated for 2 mo with a combination of LH-RH agonist [D-Trp6]LH-RH or antagonist [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6 Ala10]LH-RH (SB-75) and bombesin/GRP antagonist D-Tpi6, Leu13 psi(CH2NH)Leu14bombesin(6-14) (RC-3095). The results were compared to those obtained by treatment with same doses of single peptides. LH-RH analogs and bombesin antagonist given alone significantly reduced the number of tumorous animals and decreased weight of pancreata by 46-71% and weight of tumorous pancreas by 38-64%. Histology showed lower mitotic activity and a decreased number of AgNORs in tumor cells from treated animals. Enhanced apoptosis was also observed after treatment with the LH-RH analogs. Combination therapy had no superior inhibitory effect on tumors compared to single peptides, by practically all the parameters analyzed. The reasons for this lack of potentiation are not clear. The tumor inhibitory effect of bombesin antagonists appears to be mediated by interference with EGF-receptor mechanisms. In the present study, although a significant downregulation of EGF-receptors was found in tumors treated with combination, the decrease in binding capacity for EGF was maximal in the group treated with RC-3095 alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868941 TI - Collagenolytic activity in human pancreatic tissue with different degrees of fibrosis. AB - The present study was designed to establish a valid method for expressing collagenolytic activity in pancreatic tissue with different degrees of fibrosis. Collagenolytic activity was measured in pancreatic tissue of control and alcoholic chronic pancreatitis (CP) patients and data were expressed as percent digestion/mg tissue or as percent digestion/mg protein obtaining different results. The values were 18.4 +/- 4.7% digestion/mg tissue in the control group, and 8.4 +/- 3.2% digestion/mg tissue in the chronic pancreatitis group (p < 0.001). When collagenolytic activity was expressed as percent digestion/mg protein, measured by the Bradford assay, the values of the control group were 190.2 +/- 69.0% digestion/mg protein, and those of chronic pancreatitis patients were 187.2 +/- 61.7% digestion/mg protein (p = ns). Protein determination in pancreatic tissue of control and CP patients was seen to be influenced by the method assayed. Protein content per mg of fresh tissue, measured by the methods of Lowry, Bradford, and Bradford-SDS, were similar and twofold higher in controls than in CP samples. However, the Kjeldahl assay showed that protein content per mg of dry tissue was the same in both groups. The high degree of fibrosis in the pancreas of CP patients (60.2 +/- 28.0%) with regard to controls (4.7 +/- 1.8%) (p < 0.001) and the low response of collagen proteins to the Lowry and Bradford assays could explain the differences observed in protein content of human samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868942 TI - Bile acid malabsorption as a cause of hypocholesterolemia seen in patients with chronic pancreatitis. AB - A determination of caloric consumption based on a dietary survey table, fat and cholesterol intake, and analyses of fecal fatty acids and neutral sterols, and bile acid analysis (gas chromatographic method) were conducted on 33 subjects (including 17 patients with chronic pancreatitis and 16 normal controls). The factors related to hypocholesterolemia in chronic pancreatitis (CP) patients were investigated and the following conclusions were obtained: (1) The total caloric intake and fat consumption by the CP patients were significantly lower with the exception of cholesterol consumption. (2) Significant increases were noted in fecal fat, neutral sterols, and bile acid excretion by the CP patients. (3) A significant positive correlation was noted between the total cholesterol and body mass index (BMI), reaffirming that the cholesterol level can be used as an indicator of nutritional status. (4) A significant negative correlation was noted between the serum total cholesterol and fecal bile acid excretion. These findings indicate that CP patients suffer from neutral sterol malabsorption, in addition to dietary fat maldigestion and bile acid malabsorption. Furthermore, bile acid malabsorption is cited as a factor in the development of hypocholesterolemia in CP patients. PMID- 7868943 TI - Characterization of three cloned cell lines from a N-nitrosobis(2 hydroxypropyl)amine-induced transplantable hamster pancreatic ductal adenocarcinoma. AB - To investigate characteristics of pancreatic carcinoma growth behavior, the cloned cell lines, HPD1NR, HPD2NR, and HPD3NR, were established from a transplantable hamster ductal adenocarcinoma induced by N-nitrosobis(2 hydroxypropyl)amine (BHP). All three clones showed similar epithelial cell morphology and grew as sheets in culture with no differences in doubling times, ranging from 23-28 h. Mutation in the c-Ki-ras exon 1 was detected in common. The modal chromosome numbers were also found to be similar at 60, 62, and 60-62 in the less than tetraploid cells in the three clones. In contrast, a clear difference in frequencies of tetraploid or polyploid cells at 24.7, 22.5, and 75.5% in HPD1NR, HPD2NR, and HPD3NR, respectively, was evident. Tumorigenic potency evaluated by transplanting individual clones revealed HPD3NR to display pronouncedly less growth in syngeneic hamsters. The results suggest that increase in frequency of tetraploid or polyploid cells might be associated with a decreased in vivo growth potential of hamster pancreatic ductal adenocarcinomas, and suggest that these clones might become a valuable tool for understanding in vivo growth mechanisms of cancer cells. PMID- 7868944 TI - Bifid pancreas. An unusual anomaly associated with acute pancreatitis. AB - Pancreatic divisum and the ectopic pancreas are well-known anatomic anomalies. However, the bifid pancreatic duct is less common and is still poorly understood. The present case report examines this anatomic variant. We observed a bifid pancreatic duct in an elderly man with abdominal pain and an elevated level of serum amylase. An endoscopic papillotomy resulted in clinical improvement. PMID- 7868945 TI - Investigational Strategies for Detection and Intervention in Early-Stage Pancreatic Cancer. April 24-27, Annapolis, Maryland. Abstracts. PMID- 7868946 TI - Genetic control of susceptibility to leprosy in French Polynesia; no evidence for linkage with markers on telomeric human chromosome 2. AB - Several lines of evidence have suggested a role of genetic factors in susceptibility to leprosy. In the mouse, natural susceptibility to infection with mycobacteria is controlled by the chromosome 1 Bcg locus, a region which is syntenic with a fragment of the human chromosome 2q, region q31-q37. It has been postulated that a human homolog of the Bcg gene controls susceptibility to leprosy per se, and may be located on chromosome 2q. In order to test the influence of this putative gene on leprosy per se, we performed linkage analyses in a set of seven multicase French Polynesian pedigrees, using an affected sib pair method and the LOD score method employing different modes of inheritance. Family members were typed for eight polymorphic loci on chromosome 2q: CRYGP1, FN, TNP1, VIL, DES, INH, PAX3, and UGT1A1. Our data provide evidence against the presence of a gene controlling susceptibility to leprosy per se on human chromosome 2q in the French Polynesian population. PMID- 7868948 TI - Leprosy and infection with the human immunodeficiency virus in Uganda; a case control study. AB - Both leprosy and infection with the human immunodeficiency virus (HIV) are endemic in Uganda. Various speculations about a possible interaction between the two infections have been put forward but not confirmed. A case-control study involving 189 new leprosy patients and 481 matched controls, resident in eight Ugandan districts, was carried out to investigate if any relationship exists between leprosy and infection with HIV-1 in Uganda. Serum samples from 23 (12.2%) of the 189 leprosy patients tested positive for HIV-1 antibodies as compared to 88 (18.3%) of the 481 control sera. The two proportions of HIV seropositivity are not different statistically. A stratified analysis of the data by districts was done and showed a negative relationship between leprosy and HIV infection in the case of Rakai District (0.04 < odds ratio < 0.61, p = 0.002). It is recommended that studies seeking to observe the clinical progress of dually infected patients might help to reveal new knowledge about a possible relationship between HIV and leprosy and about the immunology of leprosy in general. PMID- 7868947 TI - A colorimetric PCR method for the detection of M. leprae in skin biopsies from leprosy patients. AB - A one-tube nested polymerase chain reaction (PCR) method for the diagnosis of paucibacillary leprosy was developed using the repetitive RLEP sequence as a target. Detection of the PCR products was simplified by the adaptation of a colorimetric method. The test was specific for Mycobacterium leprae, and the sensitivity of the assay was 1 fg of purified genomic M. leprae DNA (less than one genome). Complete concordance was seen between the development of color and resolution on agarose gels. The results of frozen skin sections from untreated patients showed that the assay could detect 100% of multibacillary samples [bacterial index (BI) of 2 or more] and 69% and 70% of the samples with BIs of 1 and 0, respectively. The use of one-tube nested PCR in assessing the effectiveness of multidrug therapy (MDT) in leprosy also was determined. The simplified colorimetric assay was found to be sensitive, rapid and specific, and is suitable for use in routing diagnostic laboratories. PMID- 7868949 TI - Prevalence of HIV infection and high-risk characteristics among leprosy patients of south India; a case-control study. AB - With the observation of the occurrence of the human immunodeficiency virus (HIV) infection among leprosy patients in our pilot study carried out in Tamil Nadu, South India, a case-control study was planned to explore whether HIV infection is a risk factor for leprosy and to understand the characteristics of HIV infection and high-risk behaviors among leprosy patients. We screened 556 patients and 1004 nonleprosy controls (matching 502 cases for age, sex and area of residence) for HIV-1 and HIV-2 antibodies. They also were interviewed for personal information on history of blood transfusion, intravenous drug abuse, high-risk sexual behavior, and sexually transmitted diseases. Of the 1019 total cases screened (of both pilot and extended studies), 5 were found to be position for HIV antibodies (HIV-1 = 4, HIV-2 = 1); of the 1019 nonleprosy controls, 6 were positive for HIV 1 antibodies. An analysis by odds ratio revealed no association between leprosy and HIV infection (OR = 0.824, 95% CI = 0.201-3.593). A strong association was found only between high-risk behavior and HIV infection (OR = 5.186, 95% CI = 1.717-15.667). However, unmarried, unmarried after 30 years of age, exposure to spouses of the leprosy patients, and a history of surgery were all observed to be significantly more common among leprosy patients than the controls. PMID- 7868950 TI - Protective effect of BCG against leprosy and its subtypes: a case-control study in southern Vietnam. AB - A case-control study was conducted to assess the protective effect of intradermal BCG against leprosy and its subtypes in southern Vietnam. A total of 177 cases were selected with a distribution by subtypes as follows: 38 TT, 23 BT, 51 BB, 36 BL, 22 LL, and 7 indeterminate. Two controls were matched with a case for age, sex, ethnic group, socioeconomic status, and district area. The odds ratio assessing the protective effect of BCG varied from 0.44 (0.19-1.03) in the BB subtype to 3.00 (0.24-37.5) in indeterminate leprosy; whereas its overall value was 0.71 (0.45-1.10) for leprosy per se. When all borderline leprosy types were pooled, the protective effect of BCG was found significant with an odds ratio of 0.48 (0.27-0.84). In the polar forms of leprosy, TT and LL, the odds ratio was > 1 with large confidence intervals. It is possible that BCG induces a shift in the immune response to a higher level of cell-mediated immunity. When BCG vaccination is given after primary infection with Mycobacterium leprae, this shift could be the cause of an increase in the risk of the occurrence of milder and transient forms of the disease. In TT forms BCG might reinforce the preexisting subclinical immunopathological reactions, and in stable LL forms BCG might be unable to induce any protective form of immunity. These results confirm the important variability in the protection offered by BCG with respect to the different types of leprosy, and may have important implications for the design and the interpretation of vaccine trials that should take into account the respective proportions of leprosy forms observed in the study region. PMID- 7868951 TI - Epidemiological studies in children of a low-endemic region, a high-endemic region, and dwellers of a leprosy colony: evaluation of anti-ND-BSA antibodies and lepromin response. AB - Children residing in a low-endemic region (LER), a high-endemic region (HER), and a leprosy colony contact population (CP) were evaluated for lepromin response as well as reactivity to the Mycobacterium leprae-specific synthetic antigen, ND BSA. The mean reactivity to ND-BSA in the LER group (OD 0.03 +/- 0.03, N = 71) was significantly lower (p < 0.001) than that in the contact population (OD 0.14 +/- 0.09, N = 140) as well as the population residing in the HER (OD 0.09 +/- 0.08, N = 1340). ELISA-positive results were the highest (21.4%) with the CP group and lowest (0.0%) in the LER group, suggesting that it was a measure of the extent of exposure of M. leprae. In the contact population, females showed a preponderance for ELISA positivity over males (p < 0.005), a finding not observed with the HER population. The Mitsuda responses showed a Gaussian-type distribution in all of the three populations examined with the mean response being highest in the LER (6.0 mm +/- 2.9) and lowest in the HER (4.5 mm +/- 2.0) groups. The percent positivity for the Mitsuda reaction was found to be highest in the LER (93.0%) and lowest in the HER (88.3%) groups. The Mitsuda response thus appears to be independent of M. leprae exposure, and its interpretation in a given population needs consideration of several factors, such as nutritional, environmental, etc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868952 TI - Current profile of active leprosy in Greece; a five-year retrospective study (1988-1992). AB - The epidemiological characteristics of newly diagnosed, active leprosy cases (incidence, N = 16 Greeks and 4 expatriates) and relapsed cases (recurrences, N = 25, all Greeks) were studied. Most of the cases were multibacillary, over 50% being lepromatous. The relapses were analyzed by sex, disease duration and residence (rural or urban). Most of the newly diagnosed cases presented with nonreactional skin lesions (70%). The relapses were self-reported and detected mainly because of type 2 leprosy reactions (56%). The main source of the infection for new cases was members of their former extended family. The statistical trend of leprosy in Greece is a continuing decline in a country which already has a very low endemicity. PMID- 7868953 TI - A longitudinal study of immunologic reactivity in leprosy patients treated with immunotherapy. AB - More than 150 leprosy patients treated with multidrug therapy (MDT) plus immunotherapy (IMT) with a mixture of heat-killed Mycobacterium leprae plus live BCG were studied in relation to humoral and cell-mediated immune responses. Many previously had received prolonged sulfone monotherapy. Patients received 2 to 10 doses of IMT in a period of 1 to 3 years, depending upon their clinical form of leprosy. The patients were followed up for 5 to 10 years with repeated determinations of antibody levels to phenolic glycolipid-I; lymphoproliferative (LTT) responses to soluble extract of M. leprae, to whole bacilli and to BCG, skin-test responses and bacterial indexes (BIs). After MDT plus IMT there was a statistically significant decrease of antibody levels in the multibacillary (MB) group. The BI decreased proportionally to the ELISA results. LTT increased to M. leprae antigens, especially to soluble extract, in a high percentage of these patients (34% of LL patients positive). Lepromin positivity in MB patients increased from 5% initially positive to 75% at the cut-off during this follow up. These results show substantial early and persistent cell-mediated reactivity to M. leprae in many MB patients treated with MDT-IMT, confirming and expanding previously published data. PMID- 7868954 TI - Epidemiologic characteristics of leprosy reactions. AB - An 8-year prospective study of a cohort of 176 newly diagnosed leprosy patients was conducted to examine the possible influence of age, sex, multidrug therapy (MDT), and duration of illness on the risk of either type 1 or type 2 reactions. Patients were enrolled over a 5-year period (1984-1989) and followed for a minimum of 3 years. All reactions studied were severe enough to warrant hospital admission. Overall, 45% of this cohort developed a reaction; 32% of patients considered at risk developed type 1 reactions, and 37% of patients considered at risk developed type 2 reactions. Despite the predominance of men among the leprosy patients, type 1 reactions occurred with significantly greater frequency in women, and did not appear to be influenced by age of onset of leprosy. Individuals experiencing one type 1 reaction were not likely to experience a recurrence, suggesting that the immunologic mechanisms of this reaction may be limited or regulated by genetic or immunologic factors. Type 2 reactions, on the other hand, occurred with equal frequency in both males and females, but were highly associated with onset of leprosy in the second decade of life. Individuals who experienced type 2 reactions often had one or more recurrence of the reaction. No increased risk was seen for either reaction with longer duration of leprosy or longer duration of treatment. The mechanisms by which these differences relate to the pathogenesis of leprosy reactions remains unclear, but future studies of clinical and immunological parameters of leprosy reactions may benefit from stratification of data by gender and age of onset of leprosy in addition to the routine grouping of results by leprosy classification. PMID- 7868955 TI - Efficacy of minocycline in single dose and at 100 mg twice daily for lepromatous leprosy. AB - A clinical trial of minocycline in a total of 10 patients with previously untreated lepromatous leprosy was conducted in order to evaluate the efficacy of a single, initial, 200-mg dose and 100 mg twice daily of minocycline for a total duration of up to 3 months. Patients improved remarkably quickly. Although single dose therapy did not result in a significant killing of Mycobacterium leprae, viable M. leprae were cleared from the dermis regularly by 3 months of twice daily therapy, a rate similar to that achieved by minocycline 100 mg once daily. Because more side effects were noted herein than previously with 100 mg daily, we recommend that minocycline, when applied, be administered at 100 mg daily to leprosy patients. PMID- 7868956 TI - Lipid composition of the stratum corneum of the sole in patients with leprosy. AB - Several reports support the view that changes of composition of the stratum corneum (SC) lipids may be the cause of impaired barrier function which, in turn, gives rise to xerosis and ichthyotic skin in leprosy. Many reports about abnormalities of serum lipids and cutaneous manifestations, such as xerosis and ichthyotic changes in leprosy, led us to the idea that the composition of SC lipids in patients with leprosy may be different from that in normal subjects. However, the many studies done in the past do not sufficiently account for this. To investigate the composition of SC lipids in patients with leprosy, thin-layer chromatography (TLC) was undertaken. Extraction of the SC lipids with a methanolchloroform-H2O mixture (4:2:1.6, v/v/v, Bligh-Dyer solvent) was carried out after shaving of the SC from the sole. TLC was performed and the composition of lipids was quantitated by photodensitometry. Our study revealed that the composition of SC lipids in the anesthetic lesions of leprosy patients was higher in cholesterol sulfate and triglycerides and lower in sphingolipids and cholesterol esters than that of normal subjects. PMID- 7868957 TI - Calcium metabolism and its regulating hormones in patients with leprosy. AB - Calcium metabolism was studied in 47 patients with borderline or lepromatous leprosy. Total and ionized calcium, phosphorus, creatinine, total alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxy vitamin D [25(OH)D], and 1,25 dihydroxy vitamin D [1,25(OH)2D] were measured in serum; calcium and total hydroxyproline were determined in urine. Total subperiosteal diameter and medullar cavity diameter were measured on an X-ray of the hand of all patients. Average values were within normal ranges for all of the biochemical determinations. Total serum calcium was moderately below the normal range in eight patients but ionized calcium levels were within the normal ranges in all of the patients. Four patients, all of them with lepromatous leprosy, had levels of 1,25(OH)2D higher than normal but none of them was hypercalcemic and PTH levels were within normal range. Although all values were within the normal ranges, lepromatous leprosy patients had lower total calcium, higher alkaline phosphatase, and higher urinary hydroxyproline than borderline leprosy patients (9.1 +/- 0.4 vs 9.4 +/- 0.3 mg%, p < 0.001; 10.3 +/- 2.9 vs 7.4 +/- 2.3 King Armstrong units, p < 0.02 and 27.2 +/- 12 vs 19.4 +/- 5.6 mg/24 hr, p < 0.02, respectively). No differences were found between patients and controls in the average micrometric measurements of the second metacarpal bone but significant osteopenia was found in 19% of the patients. The main finding of the present study in a representative sample of leprosy patients is that the average total serum calcium was in the lowest limit of the normal range, but the ionized serum calcium was in the middle of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868958 TI - Study of nerve conduction velocity, somatosensory-evoked potential and late responses (H-reflex and F-wave) of posterior tibial nerve in leprosy. AB - The present study was conducted in 25 leprosy patients (of different age and sex) with or without clinical evidence of neuropathy. The diagnosis was confirmed by skin biopsy. A group of 15 age- and sex-matched, healthy persons also were studied for comparison and served as controls. Motor nerve conduction velocity (MNCV) was reduced in nine patients (36%) and sensory nerve conduction velocity (SNCV) was reduced in three patients (12%). Late responses (H-reflex and F-wave) were deranged in 16 patients (64%). Somatosensory evoked potential (SSEP) was deranged in 13 patients (52%). N7-N18 interpeak latency (PCT) was prolonged in two patients (8%); none showed prolongation of N18-N35 interpeak latency (CCT). We observed that nerve conduction velocity, late responses, and SSEPs were deranged in all types of leprosy, regardless of clinical evidence of neuropathy, and were more prominently affected in the tuberculoid (TT) type of leprosy. A study of late responses is more informative than conventional nerve conduction studies for the detection of early lesions of the nerves. The study of SSEP shows involvement of the peripheral part of the nervous system and complete sparing of the central part of the nervous system. PMID- 7868959 TI - The microbiology of Mycobacterium leprae, Part II. Reflections on major developments and those responsible for them. PMID- 7868960 TI - Sustainability of leprosy control services in low-endemic situations. PMID- 7868961 TI - Milia in leprosy. PMID- 7868962 TI - HIV-1 infection and leprosy. PMID- 7868963 TI - Experimental transmission of human leprosy bacilli in foot pads of severe combined immunodeficient mice. PMID- 7868964 TI - Accurate diagnosis of tuberculosis meningitis using polymerase chain reaction. PMID- 7868965 TI - Mycobacterium lepraemurium itself does not interfere with the in vitro lymphoproliferation induced by concanavalin A. PMID- 7868966 TI - Electron microscopic observations of small unmyelinated nerve tissue proper in a dermal lesion of a relapsed lepromatous patient. PMID- 7868967 TI - Relapse after long-term follow up of multibacillary patients treated by WHO multidrug regimen. PMID- 7868968 TI - 29th Joint Leprosy Research Conference. Kyoto, Japan, 19-22 August 1994. Abstracts. PMID- 7868969 TI - Cell density can affect cholesteryl ester accumulation in the human THP-1 macrophage. AB - Esterified cholesterol (EC) accumulation was induced in THP-1 macrophages after exposure to acetylated LDL (acLDL), and the extent of accumulation was dependent on cell density. EC mass was 5-fold greater in cells plated at 1.0 x 10(6) cells/35 mm dish compared to cells plated at density 4.0 x 10(6) cells/dish. In addition, [14C]oleate incorporation into EC also increased with decreasing cell number, with 4-fold greater incorporation (6 h: 177 +/- 0.014 vs. 45 +/- 0.001 pmol/mg cell protein, P < 0.001; 24 h: 515 +/- 0.037 vs. 120 +/- 0.012 pmol/mg, P < 0.001) in cells plated less densely compared to cells plated at a higher density. The rate of 125I-labeled acLDL degradation was about 2-fold greater in cells plated at the lower density (105 vs. 60 ng/h per mg cell protein). Northern analysis showed a 2-fold reduction in the expression of human scavenger receptor mRNA in density plated cells, and immunoprecipitation also demonstrated a 2-fold decrease in scavenger receptor protein. Conditioned media did not differentially affect EC formation at either cell density. Fatty acid supplementation increased EC formation and the proportion of esterified sterol content only in cell plated at the higher density. The fatty acid effect was also seen when cells were exposed to beta-VLDL, which induced comparable levels of EC accumulation by non scavenger receptor-mediated processes in densely plated cells. Foam cell formation in THP-1 macrophages may depend on cell density, which appears to affect both scavenger and non-scavenger receptor activity. PMID- 7868970 TI - Transcriptional regulation of the apoC-III gene by insulin in diabetic mice: correlation with changes in plasma triglyceride levels. AB - Insulin-dependent diabetes mellitus (IDDM) is associated with elevated plasma triglyceride levels that normalize after insulin administration. The observation that overexpression of the apoC-III gene in transgenic mice can cause hypertriglyceridemia and other evidence implicating apoC-III in the regulation of triglyceride levels prompted us to examine whether apoC-III might be involved in the hypertriglyceridemia associated with IDDM. To this end, the regulation of apoC-III gene expression was studied in the streptozotocin-treated mouse model of IDDM. In the insulin-deficient diabetic state, these mice have elevated glucose and triglyceride levels and a 1.4- to 1.5-fold increase in hepatic apoC-III mRNA levels, by Northern analysis as well as quantitative solution hybridization RNase protection assay. Insulin treatment normalized the glucose and triglyceride levels and diminished hepatic apoC-III mRNA levels by 59%. Analysis of transcription rates using the nuclear run-on technique demonstrated that the changes in hepatic apoC-III mRNA levels were the results of changes in the transcriptional activity of the gene. To determine the role of insulin in the regulation of apoC-III transcription, HepG2 cells were transfected with an apoC III reporter construct, and treated with different insulin concentrations. The results demonstrated that insulin treatment induced a dose-dependent down regulation of apoC-III transcriptional activity. These data suggest that the apoC III transcriptional changes seen in animals are caused by differences in insulin concentrations. Assuming that apoC-III mRNA levels reflect the synthesis and secretion of the protein, these results present the possibility that overexpression of the apoC-III gene could contribute to the hypertriglyceridemia observed in IDDM. PMID- 7868971 TI - NMR lipid profiles of cells, tissues, and body fluids: proton NMR analysis of human erythrocyte lipids. AB - One- and two-dimensional high resolution NMR spectroscopy was applied to determine quantitatively and qualitatively the lipids extracted from human erythrocyte membranes. The relative amounts of the major lipids were determined from the spectra of unfractionated lipid extracts. After HPLC fractionation of the lipid extracts and NMR analysis of the fractions, it was possible to determine the features of the component lipids of each lipid class and to compare, especially, the fatty acid types and composition of the individual major glycerophospholipids. The results of this proton NMR analysis were compared to those obtained elsewhere using classical lipid analytical techniques and found to be in substantial agreement. PMID- 7868972 TI - Structures and stereochemistry of the very long alpha, omega-bifunctional alkyl species in the membrane of Sarcina ventriculi indicate that they are formed by tail-to-tail coupling of normal fatty acids. AB - In a previous study, we demonstrated that Sarcina ventriculi is capable of adjusting to alterations in environmental conditions (such as increase in temperature, lowering of pH, or addition of exogenous organic solvents) by the synthesis of a family of alpha, omega-dicarboxylic acids ranging from 28 to 36 carbons long (Jung, S., et al. 1993. J. Biol. Chem. 268: 2828-2835). The chain lengths and relative abundance of the very long dicarboxylic acids found in S. ventriculi suggest that they may be formed after the perturbation by the (enzymatic) tail-to-tail combinations of existing regular monofunctional fatty acids and not completely de novo by direct 2-carbon addition of acetyl coenzyme A (CoA). If this were true, knowing the structures of the regular fatty acids, we can predict those of the very long chain bifunctional acids. In this work we present definitive chemical results that strongly support this mechanism. This was done by analyzing the structures and stereochemistry of the very long bifunctional species in the light of those of the regular monofunctional species. The exact structures of membrane fatty acid methyl ester derivatives components were determined by various spectroscopic and chemical methods including gas chromatographic (GC) analysis, gas chromatography-mass spectrometry (GC-MS), 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, polarimetry, and reductive ozonolysis. This yielded precise structural and stereochemical information on the position of substitution of the acyl chain by methyl groups, position and configuration of double bonds, and optical activity. These results, coupled with the absence of intermediate length acyl species, indicated that the very long alkyl species (without exception) can be formed by tail-to-tail joining of existing fatty acids. The ideas of a dynamically regulated catalytic system is proposed. PMID- 7868973 TI - Acute and chronic effects on cholesterol biosynthesis of LDL-apheresis with or without concomitant HMG-CoA reductase inhibitor therapy. AB - To determine the acute and long-term effects of low density lipoprotein (LDL) reduction on cholesterol biosynthesis, we studied changes in the cholesterol precursors mevalonic acid (MVA) and lathosterol in patients with heterozygous familial hypercholesterolemia undergoing LDL-apheresis. Long-term LDL-apheresis in eight patients resulted in slight but insignificant increases in plasma MVA levels and lathosterol/cholesterol (L/C) ratios over 18 months. In short-term studies, six patients not on drugs and six patients treated with lovastatin or pravastatin had blood taken immediately before and after LDL-apheresis, and afterwards on days 1, 2, 3, 5, and 7. Plasma L/C ratios and MVA concentration did not change significantly on the first day after LDL-apheresis in those not on statin therapy (1.11 +/- 0.08 vs. 1.40 +/- 0.18, and 9.2 +/- 1.3 vs. 9.1 +/- 0.6 ng/ml, respectively) but increased in the statin-treated group (from 0.78 +/- 0.09 to 1.55 +/- 0.21, P = 0.003 and from 5.0 +/- 0.7 to 11.0 +/- 1.6 ng/ml, P = 0.008, respectively). There was no clear correlation between the changes in either of these precursors and the extent of reduction of total cholesterol by LDL-apheresis, but there was a strong inverse correlation with the post-apheresis LDL-cholesterol level (r = -0.77, P = 0.002 for L/C ratio; r = -0.75, P = 0.003 for MVA). Post-apheresis changes in L/C ratio and MVA were mutually correlated (r = 0.68. P = 0.01). We conclude that LDL-apheresis stimulates cholesterol biosynthesis transiently despite concomitant therapy with an HMG-CoA reductase inhibitor, the degree of stimulation being inversely related to the level to which the LDL-cholesterol was reduced. PMID- 7868974 TI - Effect of Golgi membrane phospholipid composition on the molecular species of GM3 gangliosides synthesized by rat liver sialyltransferase. AB - Previous studies have demonstrated that there is a change in the molecular species specificity of CMP-N-acetylneuraminate:lactosylceramide alpha 2,3 sialyltransferase (LacCer alpha 2,3-ST) when the lipid composition of the Golgi membrane is altered (Kadowaki, Grant, and Williams, 1993. J. Lipid Res. 34: 905 914). To understand the basis of this phenomenon, the molecular species specificity of rat liver LacCer alpha 2,3-ST was determined under conditions in which the phospholipid class composition of the Golgi membrane was changed to resemble that of cultured mouse neuroblastoma NB2a cells, a cell line in which LacCer alpha 2,3-ST exhibits no molecular species specificity. The change in the lipid composition of the Golgi membrane was accomplished by incubating the Golgi membrane vesicles with nonspecific lipid transfer protein and a 10-fold excess of liposomes prepared with various proportions of purified rat liver lipids. The molecular species specificity of LacCer alpha 2,3-ST was also determined under conditions where the phospholipid molecular species composition but not the phospholipid class composition of the Golgi membrane was changed, and in which both the phospholipid class and molecular species compositions were changed by using liposomes prepared with lipids purified from a mouse brain tumor (ependymoblastoma). When using liposomes prepared with rat liver lipids, a change in the phospholipid class composition of the Golgi membrane to a composition similar to that of NB2a cells increased rather than decreased the molecular species specificity of rat liver LacCer alpha 2,3-ST.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868975 TI - Effect of apolipoprotein E phenotype on diet-induced lowering of plasma low density lipoprotein cholesterol. AB - The National Cholesterol Education Program (NCEP) has recommended that dietary total fat, saturated fat, and cholesterol intake be reduced to < or = 30% of calories, < 10% of calories, and < 300 mg/day, respectively (Step 1 diet) in the general population to reduce plasma low density lipoprotein (LDL) cholesterol levels and heart disease risk. We examined the LDL cholesterol-lowering response to such a diet (26% fat, 8% saturated fat, and 201 mg/day of cholesterol) as compared to an average American diet (39% fat, 15% saturated fat, and 435 mg/day of cholesterol) in 128 subjects using diet periods of 4-24 weeks for each diet phase. The mean LDL cholesterol reduction was 15% in males (n = 83) and 8% in post-menopausal females (n = 45). The effect of apolipoprotein (apo) E phenotype on responsiveness was examined. LDL cholesterol lowering in males was 14% for 60 apoE3/3 subjects, 23% for 10 apoE3/4 subjects, and 16% for 13 apoE3/2 subjects. Male apoE3/4 subjects had a significantly greater LDL cholesterol reduction (P = 0.006) and a greater decrease in the LDL/HDL ratio (P = 0.047) than apoE3/3 subjects. In females, 7% lowering in LDL cholesterol was observed in 34 apoE3/3 subjects and 11% lowering was observed in 7 apoE3/4 subjects (P = 0.12). A meta analysis of data from published studies supports this conclusion. These data indicate that apoE phenotype modulates the LDL cholesterol-lowering response to a diet meeting NCEP Step 1 criteria, and that male subjects carrying the apoE4 allele are more responsive than other subjects. PMID- 7868976 TI - Exchangeable apolipoproteins of insects share a common structural motif. AB - Elucidation of the secondary structure of the exchangeable apolipoproteins has been hindered by the difficulty in producing crystals suitable for X-ray spectrographic analyses. Consequently, in order to analyze potential structure function relationships in the family of insect exchangeable apolipoproteins, apolipophorins-III (apoLps-III), two apoLps-III cDNA clones, one from the palo verde beetle (Derobrachus geminatus) and one from the house cricket (Acheta domesticus), have been isolated and sequenced. Multiple sequence alignments of the deduced protein sequences with two previously reported apolipophorins-III from Manduca sexta and Locusta migratoria reveal low sequence identity, suggesting that these proteins are very old and are highly divergent. Computer assisted predictions of protein structure and subsequent analyses, using the known secondary structure of Locusta migratoria apolipophorin-III as a control, indicate that these insect proteins are composed of five amphipathic helices with characteristics similar to those of the helical domains of the mammalian exchangeable apolipoproteins. Thus, although insect and vertebrate exchangeable apolipoproteins share a common function in assisting lipid transport, precise amino acid identity is less important than the common structural feature of multiple amphipathic helices. Moreover, because these proteins occur widely among insect species, even in those where flight is limited or absent, we hypothesize that apolipophorin-III has a more generalized function in lipid metabolism than had been previously proposed. PMID- 7868977 TI - Effect of vitamin A deficiency and retinoic acid repletion on intestinal and hepatic apolipoprotein A-I mRNA levels of adult rats. AB - Apolipoprotein A-I (apoA-I) gene expression is known to be regulated by nutritional and hormonal factors. Experiments were conducted to determine the effects of vitamin A deficiency and retinoic acid repletion on the in vivo expression of apoA-I in rat intestine and liver. The relative abundance of apoA-I mRNA (apoA-I/beta-actin ratio) in the intestine did not differ significantly between vitamin A-deficient and -sufficient rats. However, the relative abundance of hepatic apoA-I mRNA of vitamin A-deficient rats was 2.2- to 6-times that of sufficient rats. Even marginal vitamin A status resulted in a significant increase in hepatic apoA-I mRNA expression. Treatment of vitamin A-deficient rats with a single dose of retinoic acid (20 micrograms, 20 h before tissues were collected) reduced the hepatic apoA-I mRNA/beta-actin ratio by about 40%, while further reduction (about 60-65%) was observed after two treatments with retinoic acid. By nuclear run-on assay, the increase in hepatic apoA-I mRNA in vitamin A deficient rats was attributable to increased transcription of the apoA-I gene. However, immunoblot analysis showed no apparent differences in apoA-I protein in either liver homogenates or plasma of vitamin A-deficient and -sufficient rats. These data indicate that apoA-I gene expression in vivo is sensitive to retinoid status and suggest that there is additional regulation of post-transcriptional events. PMID- 7868979 TI - A newly identified heterozygous lipoprotein lipase gene mutation (Cys239- >stop/TGC972-->TGA; LPLobama) in a patient with primary type IV hyperlipoproteinemia. AB - We investigated measures for identification of heterozygous lipoprotein lipase (LPL) deficiency in unrelated subjects with primary type IV hyperlipoproteinemia in order to acquire a helpful clue for understanding the correlation between hypertriglyceridemia and the status of being a heterozygous carrier of an LPL gene variant. Identification of heterozygous LPL deficiency was performed by monitoring the immunoreactive LPL mass in postheparin plasma (PHP) using our developed sandwich-enzyme immunoassay technique for first screening. Then, in subjects found to have half or less than half of the control LPL mass value in PHP, the polymerase chain reaction-single strand conformation polymorphism method was used to detect LPL gene aberrations as a second screening. This approach was evaluated as being useful as it succeeded in identifying a subject (proband KD) with heterozygous LPL deficiency. The mutation in the LPL gene of proband KD was newly characterized as a nucleotide C972 to A transversion in exon 6, resulting in substitution of a premature termination codon (TGA) for Cys239 (TGC). This nonsense mutation, designated as LPLobama, creates an MboI restriction site and eliminates an HgiAI restriction site, and this allows rapid screening of subjects with type IV as well as type I hyperlipoproteinemia for the mutation. The homozygous state for the LPLobama allele resulted in neither detectable LPL activity nor immunoreactive LPL mass in PHP, and this was seen in two of proband KD's siblings. PMID- 7868978 TI - Effects of increasing amounts of dietary cholesterol on postprandial lipemia and lipoproteins in human subjects. AB - Our aim was to determine the effects of increasing amounts of dietary cholesterol (0-710 mg) on the postprandial plasma lipid responses and lipoprotein changes in normolipidemic human subjects. Ten subjects were fed five different test meals in a random order: one meal did not contain fat or cholesterol while the four others contained a fixed amount of lipids (45 g) and 0, 140, 280, and 710 mg cholesterol, respectively. Fasting and post-meal blood samples were obtained for 7 h. Large and small triglyceride-rich lipoproteins (TRL), low density (LDL), and high density (HDL) lipoproteins were isolated. Compared to the no-fat, no cholesterol meal, the fat-enriched meals raised (P < 0.05) plasma triglycerides, phospholipids, and free cholesterol and lowered cholesteryl esters postprandially. The meals containing zero or 140 mg cholesterol generally elicited comparable postprandial plasma and lipoprotein lipid responses. The meals providing 280 or 710 mg cholesterol significantly increased postprandial plasma phospholipids and large TRL triglycerides and decreased plasma esterified cholesterol. The lipid composition of the large TRLs and the concentrations of the small TRL lipid components were not altered postprandially by cholesterol intake. On the other hand, LDL free cholesterol increased after 3 h, LDL cholesteryl esters dropped after 3 and 7 h, HDL cholesteryl esters dropped after 3 h, and HDL phospholipids increased 7 h after ingesting meals highly enriched in cholesterol. Blood insulin, apoA-I and apoB were not altered postprandially by cholesterol intake. Thus, the data show that ingesting more than 140 mg cholesterol per meal significantly alters the postprandial lipoprotein response in healthy subjects. PMID- 7868980 TI - Apolipoprotein B-100 production and cholesteryl ester content in the liver of developing chick. AB - In the chick, the large cholesteryl ester (CE) store present in the liver during the last period of embryonic life increases at hatching and is rapidly depleted after 2-7 days of postnatal life. In this study we asked whether these changes were associated with variations in the hepatic production of apoB-containing lipoproteins. Liver slices taken from chicks at -3, 0 (hatching), 2, 4, 7, and 10 days of development were incubated with [35S]methionine in steady state incubations. ApoB production (cell + medium radioactivity) decreased from day -3 to day 0 (40%), increased at day 4 (54%), and decreased afterwards (45%). At day 4 the amount of 35S-labeled apoB-containing lipoproteins (VLDL-LDL) secreted into the medium was 1.7- and 1.5-times that found at days 0 and 7, respectively; the radioactivity incorporated into medium HDL (containing predominantly apoA-I) was 1.7-times that found at days 0 and 7. The incubation of liver slices with [3H]oleate showed that CE production at days 4 and 7 was 58% and 33%, respectively, of that found at day 0. The percentage of newly synthesized hepatic CE secreted into medium lipoproteins was 2.4%, 3.1%, and 2.2% at days 0, 4, and 7, respectively. The percentage of lipoprotein CE present in VLDL-LDL ranged from 38% at day 0 to 21% at day 7, and that present in HDL ranged from 62% at day 0 to 79% at day 7. To define whether the changes in the production of apoA-I- and apoB containing lipoproteins were due to variations in apoB and apoA-I synthesis, the initial synthetic rate (pulse-labeling) and the mRNA content of these apolipoproteins were investigated. The initial apoB synthetic rate decreased 1.5 fold from day -3 to day 0, remained stable up to day 7, and decreased at day 10. Hepatic apoB mRNA followed a similar trend. The synthesis of apoA-I increased 2 fold from days -3/2 up to day 4 and did not change afterwards. In conclusion the increased hepatic CE content at hatching reflects a decreased production of apoB, while the depletion of CE observed from day 2 to day 7 is associated with an increased production of both apoB- and apoA-I-containing lipoproteins. The decreased apoB production at hatching is due to a decreased apoB synthesis whereas the increased apoB production at day 4 appears to be related to a post translational event. PMID- 7868981 TI - Essential fatty acid metabolism in the feline: relationship between liver and brain production of long-chain polyunsaturated fatty acids. AB - A comparison was made between the liver and brain conversion of linoleic acid, 18:2n-6, and linolenic acid, 18:3n-3, to long chain polyunsaturated fatty acids in domestic felines. This report demonstrates that 6-desaturase activity does exist in the feline. The liver produced deuterium-labeled polyunsaturated fatty acids up to 22:4n-6 and 22:5n-3. The brain was found to accumulate the deuterium labeled polyunsaturated fatty acids, 22:5n-6, 22:6n-3, 24:4n-6, 24:5n-6, 24:5n-3, and 24:6n-3. Adult felines were provided a diet consisting of either 10% fat (hydrogenated coconut oil-corn oil 9:1) containing no 20- or 22-carbon n-6 or n-3 fatty acids or a chow diet with meat and meat by-products that contained these long chain polyunsaturated fatty acids for a 6-month period. During this time, the in vivo production of long chain polyunsaturated fatty acids was evaluated in these animals. The cats were given oral doses of both [17,17,18,18,18,2H]18:3n-3 and [9,10,12,13-2H]18:2n-6 and the deuterium-labeled fatty acid metabolites were measured in the blood, liver, and brain using a highly sensitive and specific gas chromatography-mass spectrometry technique. Contrary to previous claims, 6 desaturase activity was shown to exist in the feline. The evidence for this was the detection of [9,10,12,13-2H] 18:3n-6 which was converted from [9,10,12,13 2H]18:2n-6 and observed in the plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7868982 TI - Biliary bile acids of fruit pigeons and doves (Columbiformes): presence of 1-beta hydroxychenodeoxycholic acid and conjugation with glycine as well as taurine. AB - The biliary bile acid composition of 30 species of pigeons and doves belonging to seven genera in the avian order Columbiformes was determined using TLC, HPLC, GLC/MS, LSIMS, and NMR. In 23 of 25 species of fruit pigeons and doves, chenodeoxycholic acid was the major bile acid (> 50%). In only 1 species (Ptilinopus ornatus) was cholic the major bile acid. A number of species (7 of 15 species in the genus Ptilinopus, and 6 of 9 species in the genus Ducula) contained 1 beta,3 alpha,7 alpha-trihydroxy-5 beta-cholan-24-oic acid in proportions ranging from 2 to 43%. This 1 beta-hydroxy derivative of chenodeoxycholic acid has not been previously identified as a major biliary bile acid in vertebrates. Five of 15 species of the genus Ptilinopus, 5 of 9 species of the genus Ducula, and the only species examined for the genus Gymnophaps contained 23R-hydroxy chenodeoxycholic acid in detectable proportions, ranging from 1 to 4%. Bile acids were conjugated (in N-acyl linkage) with glycine and taurine in 28 species and with only taurine in 2 species. The fruit pigeons are the first non-mammalian genera identified to date in whom bile acids are conjugated with glycine, as well as with taurine. An incidental finding was that a gallbladder was present in 3 genera (Ptilinopus, Ducula, and Gymnophaps) and absent in 4 genera (Gallicolumba, Chalcophaps, Otidiphaps, and Treron). PMID- 7868983 TI - Mutagenesis in four candidate heparin binding regions (residues 279-282, 291-304, 390-393, and 439-448) and identification of residues affecting heparin binding of human lipoprotein lipase. AB - Lipoprotein lipase (LPL) interaction with membrane-associated polyanions is a critical component of normal catalytic function. Two strong candidate binding regions, rich in arginine and lysine residues, have been defined in the N terminal domain (aa279-282 and aa292-304) that show homology to the heparin binding consensus sequences -X-B-B-X-B-X- and -X-B-B-B-X-X-B-X-, respectively. Additional candidate regions appear in the C-terminal domain, (residues 390-393), which are homologous to the thrombospondin heparin-binding repeat, and the positively charged terminal decapeptide (residues 439-448). To determine residues and domains critical to heparin binding, we have generated different LPL mutants that have alanine substitutions of single arginine and lysine residues and sequence interchanges with the homologous hepatic (HL) and pancreatic (PL) lipases. The mutant cDNAs were expressed in COS-1 cells and catalytically active mutants were assessed for binding to heparin-Sepharose. All the alanine substitutions within the two regions homologous to the heparin-binding consensus sequences in the N-terminal domain either abolished activity or produced a lowering of heparin binding affinity. None of the mutants in the C-terminal domain of LPL showed a loss of activity or a reduction in heparin binding affinity. These data demonstrate that charged residues at positions 279-282 and 292-304 of LPL are important for heparin binding affinity whereas the residues 390-393 and 439-448 in the C-terminal domain are not involved in heparin binding. PMID- 7868984 TI - 6-Hydroxy-4-sphingenine in human epidermal ceramides. AB - The solvent-extractable lipids of human epidermal stratum corneum consist predominantly of ceramides. In addition two non-extractable ceramides are chemically bound to the stratum corneum protein. One of the bound ceramides, constituting 50% of the bound lipids, was previously shown to consist of very long chan omega-hydroxyacids in amide linkage with sphingosine. The second bound caramide, which forms 25% of the bound lipids, was shown to contain the same hydroxyacids, but the sphingoid base was neither sphingosine nor phytosphingosine. In the present study, the undefined bound ceramide was shown by NMR and chemical procedures to be the omega-hydroxyacid derivative of a new base, 6-hydroxy-4-sphingenine. In addition, a ceramide previously known to constitute 25% of the extractable human stratum corneum ceramides has been found to contain the same novel sphingoid base, amide-linked to long-chain alpha-hydroxyacids. Finally, a new acylceramide has been isolated and identified that consists of very long chain omega-hydroxyacids in amide linkage with the novel sphingolipid, with fatty acids esterified wit the terminal hydroxyl group of the hydroxyacid. PMID- 7868985 TI - Crystal structure of cholesteryl butanoate at 123 K. AB - Cholesteryl butanoate has a complex crystal structure that differs from those of the three main structure type for cholesteryl esters. It contains four molecules (C31H52O2) unrelated by crystal symmetry. The molecules are packed in almost planar sheets and have molecular long axes nearly parallel. However, the molecules have different orientations about their long axes and furthermore, in a given sheet, one of the independent molecules is antiparallel to the other three. Viewed down the molecular long axes, each molecule has six nearest neighbors, but the detailed environment is different for the four independent molecules. Thus the molecular arrangement has features that are characteristic of the short-range order present in the cholesteric mesophase. The monotropic transformation from the crystalline to the cholesteric phase occurs at 98 degrees C. The crystal structure has been accurately determined using 12,146 independent X-ray reflections having sin theta/lambda < 0.63 A-1. All hydrogen atoms were located from a difference Fourier and were included in a refinement that gave R(F2) = 0.064. The C-C bond lengths have sigma = 0.003 A and C-C-C bond angles have sigma = 0.2 degrees. Conformations for the steroid ring system are similar but there are differences in the C17 side chains and the butanoate chains of the four independent molecules. Analysis of atomic m.s. displacement tensors using a segmented-body model indicates that there are internal librations involving both the C17 and butanoate chains in all molecules. PMID- 7868986 TI - Effects of postmenopausal hormone replacement with oral and transdermal estrogen on high density lipoprotein metabolism. AB - Estrogen treatment raises plasma high density lipoprotein (HDL) levels, which may reduce cardiovascular risk. To identify the responsible mechanisms as well as the importance of the route of administration, we treated eight healthy postmenopausal women in a double-blind crossover study with three treatments for 6 weeks each: oral estradiol, 2 mg daily; transdermal estradiol, 0.1 mg twice weekly; and placebo. At the end of each treatment, apoA-I of HDL2 (d 1.063-1.125 g/ml) and HDL3 (d 1.125-1.210 g/ml) was endogenously labeled by a constant intravenous infusion of trideuterated leucine. HDL2 and HDL3 were separated by preparative ultracentrifugation. The pool sizes and enrichment curves of HDL apoA I were used to calculate production rates and fractional catabolic rates (FCR). Oral estradiol increased the levels of HDL2 apoA-I by 37% (P < 0.005) and of HDL3 apoA-I by 11% (P < 0.05). These increased apoA-I levels resulted entirely from increased production, by 36% for HDL2 (P < 0.01), and by 19% for HDL3, (P < 0.05) as their FCRs were unchanged (0.20 pool/d with placebo and 0.21 with estradiol for HDL2, and 0.19 with placebo and 0.21 with estradiol for HDL3). The isotopic enrichment curves of HDL2 apoA-I and HDL3 apoA-I were identical, implying that apoA-I rapidly cycles between HDL particles, or that rapid interconversion of these subfractions occurs. The changes in HDL apoA-I metabolic rates were positively correlated with changes in VLDL-apoB metabolic rates measured previously. Transdermal estradiol, with systemic potency similar to that of oral estradiol, had no significant effect on HDL levels or metabolic rates. Thus, the "first pass" effect of oral estradiol on the liver and/or intestine appears to increase HDL apoA-I levels (particularly in HDL2) by increasing HDL apoA-I production, and not by reducing HDL apoA-I catabolism. PMID- 7868987 TI - Enhanced detection of lipid transfer inhibitor protein activity by an assay involving only low density lipoprotein. AB - Lipid transfer inhibitor protein (LTIP) activity has been typically quantitated by its ability to suppress lipid transfer protein-mediated lipid movement between low density lipoprotein (LDL) and high density lipoprotein (HDL). In an attempt to establish an LTIP activity assay that is more sensitive, we have exploited the reported preference of the inhibitor protein to interact with LDL. A lipid transfer assay was established that involves LDL as both the donor and the acceptor; LDL in one of these two pools was biotinylated to facilitate its removal with immobilized avidin. Compared to the standard LDL to HDL assay, LTIP inhibited lipid transfer from radiolabeled LDL to biotin-LDL 7-fold more. In the absence of LTIP, lipid transfer activity was the same in both assays. An added benefit of this assay was the near linearity (up to 85%) of the inhibitory response, in contrast to the highly curvilinear response of LTIP in LDL to HDL transfer assays. The high sensitivity of the LDL to biotin-LDL transfer assay in measuring LTIP activity could not be duplicated by other transfer assays including assays containing only HDL (HDL to biotin-HDL), assays between liposomes and LDL, or assays between LDL and HDL where the concentration of lipoproteins was reduced 10-fold. Thus, LTIP activity is most effectively measured in homologous lipid transfer assays involving only LDL (and its biotin derivative). This increased sensitivity to LTIP suggests that the inhibitor binds more avidly to the LDL surface than does lipid transfer protein. PMID- 7868988 TI - Removal of borate from tritiated gangliosides via the mannitoborate complex. AB - Purified gangliosides were radiolabeled by exposure to sodium boro [3H]hydride in the presence of palladium on barium sulfate. After centrifugation to remove the catalyst, borate was complexed with mannitol and the resulting mannitoborate complex and salts were removed by reversed phase chromatography. The labeled gangliosides were repurified by ion exchange and silica gel chromatographies. Radiopurity was determined by autoradiography of two-dimensional thin-layer chromatograms of the gangliosides. The method eliminates the need for extensive dialysis or repeated methanol evaporations to remove borate thus reducing time and the volume of labeled waste. PMID- 7868989 TI - Immune networks modeled by replicator equations. AB - In order to evaluate the role of idiotypic networks in the operation of the immune system a number of mathematical models have been formulated. Here we examine a class of B-cell models in which cell proliferation is governed by a non negative, unimodal, symmetric response function f (h), where the field h summarizes the effect of the network on a single clone. We show that by transforming into relative concentrations, the B-cell network equations can be brought into a form that closely resembles the replicator equation. We then show that when the total number of clones in a network is conserved, the dynamics of the network can be represented by the dynamics of a replicator equation. The number of equilibria and their stability are then characterized using methods developed for the study of second-order replicator equations. Analogies with standard Lotka-Volterra equations are also indicated. A particularly interesting result of our analysis is the fact that even though the immune network equations are not second-order, the number and stability of their equilibria can be obtained by a superposition of second-order replicator systems. As a consequence, the problem of finding all of the equilibrium points of the nonlinear network equations can be reduced to solving linear equations. PMID- 7868990 TI - Translating stochastic density-dependent individual behavior with sensory constraints to an Eulerian model of animal swarming. AB - Density-dependent social behaviors such as swarming and schooling determine spatial distribution and patterns of resource use in many species. Lagrangian (individual-based) models have been used to investigate social groups arising from hypothetical algorithms for behavioral interactions, but the Lagrangian approach is limited by computational and analytical constraints to relatively small numbers of individuals and relatively short times. The dynamics of "group properties", such as population density, are often more ecologically useful descriptions of aggregated spatial distributions than individual movements and positions. Eulerian (partial differential equation) models directly predict these group properties; however, such models have been inadequately tied to specific individual behaviors. In this paper, I present an Eulerian model of density dependent swarming which is derived directly from a Lagrangian model in which individuals with limited sensing distances seek a target density of neighbors. The essential step in the derivation is the interpretation of the density distribution as governing the occurrence of animals as Poisson points; thus the number of individuals observed in any spatial interval is a Poisson-distributed random variable. This interpretation appears to be appropriate whenever a high degree of randomness in individual positions is present. The Eulerian model takes the form of a nonlinear partial integro-differential equation (PIDE); this equation accurately predicts statistically stationary swarm characteristics, such as expected expected density distribution. Stability analysis of the PIDE correctly predicts transients in the stochastic form of the aggregation model. The model is presented in one-dimensional form; however, it illustrates an approach that can be equally well applied in higher dimensions, and for more sophisticated behavioral algorithms. PMID- 7868991 TI - Travelling waves in a tissue interaction model for skin pattern formation. AB - Tissue interaction plays a major role in many morphogenetic processes, particularly those associated with skin organ primordia. We examine travelling wave solutions in a tissue interaction model for skin pattern formation which is firmly based on the known biology. From a phase space analysis we conjecture the existence of travelling waves with specific wave speeds. Subsequently, analytical approximations to the wave profiles are derived using perturbation methods. We then show numerically that such travelling wave solutions do exist and that they are in good agreement with out analytical results. Finally, the biological implications of our analysis are discussed. PMID- 7868992 TI - Analysis of a model of bovine brucellosis using singular perturbations. AB - In this paper a model of bovine brucellosis spread is analyzed. This model consider four epidemiological classes: susceptibles, aborting infectious, infectious carriers and immune by vaccination. The per capita death rates of susceptibles, aborting and carriers are interpreted as slaughtering rates and they are time variable in order to maintain the size of the herd constant. A description of the evolution of the disease at the beginning of the epizootiological outbreak is given by means of singular perturbation techniques. We obtain a threshold parameter for the outbreak of the disease and a description of the asymptotic behavior of the model by using a theorem of Markus on asymptotically autonomous systems. PMID- 7868993 TI - New barbarians at the gate. PMID- 7868994 TI - Health care reform ... resurgens. PMID- 7868995 TI - Election '94: a conservative tsunami floods the nation. PMID- 7868996 TI - Beware of state health reform. Inside Minnesota care. PMID- 7868997 TI - Rape versus seduction: liberty and the role of government. PMID- 7868998 TI - Medical care in Ukraine: ravaged by socialism. PMID- 7868999 TI - The politics of health care reform. AB - In many ways the reform debate is a struggle among competing ideologies. The risk we take is that the politics becomes more important than the results. For the ordinary citizen, it matters little who gets the credit. What matters is how well the system addresses the critical issues of access coverage, and cost. The choices are difficult. Those who think we have the resources necessary to conquer all our problems fail to admit that the United States is not the Garden of Eden. It would be nice if government were able to legislate away the negative effects of our human nature. But since that is impossible, we must set realistic goals and establish reasonable priorities. The challenge is before us. PMID- 7869000 TI - James B. Connolly, First modern Olympic champion. The Georgia Connection, Circa 1896. AB - As the centennial Olympic Games come to Atlanta in 1996, and the sailing venue to Savannah, it is only fitting that the first modern Olympic champion had some connection to the state of Georgia, the city of Savannah, and the art of sailing. James Brendan Connolly was not only a terrific athlete, but a noted writer and adventurer. Moreover, he was the type of man who impressed even the President of the United States with his sterling qualities. The latter serve as a shining example a century after his initial Olympic exploits. PMID- 7869001 TI - A profile of the Patient Protection Act. PMID- 7869002 TI - Pneumonia with pleural effusions. AB - One hundred and forty three among five hundred and twenty-six cases of bacterial pneumonia in adults (27.2%) who had pleural effusion (parapneumonic effusion) admitted to Chulalongkorn Hospital during the period January 1987 to December 1991 were analyzed. There were 40 cases with effusion that was less than 10 mm thick on chest decubitus film, 44 cases of uncomplicated exudative phase, 40 cases of complicated exudative phase (early empyema) and 19 cases of empyema. Most patients in our study required thoracocentesis (72%), had early empyema and emyema (41.3%) as well as high incidence of positive organisms on Gram stain in pleural fluid. This indicates that our patients may have had a prolonged clinical course before coming to the hospital. About half of our patients had pleuitic chest pain or signs of pleural effusion. Among the various stages of parapneumonic effusion, the empyema group had the most delayed response to treatment and needed intercostal drainage for twice the duration of the early empyema group (15.69 vs 7.55 days). The overall mortality was 22.4 per cent. Factors associated with death were advanced age, hospital acquired and broncho pneumonia, abnormal host, no pleuritic chest pain, no signs of consolidation, respiratory failure, shock and complications of assisted ventilation. PMID- 7869003 TI - Disability among Thai elderly living in Klong Toey slum. AB - Forty three per cent of the elderly in Klong Toey slum had BAI score less than 20. One point six per cent were moderately severe or severely disabled and needed special care. Around one-third of them caused by stroke. Locomotion, reaching and stretching, dexterity, continence and seeing are common significant types of disability among this population study. Perceived health status, age and working status are independent factors related to disability level. The Barthel ADL index is suitable for using as a tool for a disability survey among Thai elderly. The ODS questionnaire may be applied after considerable modification of the questions concerning behavior and intelligence dimensions. PMID- 7869004 TI - Clinical features and clinical course of multiple sclerosis in Thai patients: a report of 50 cases. AB - During a twenty-year period 1967-1986, clinical features and clinical course of 50 patients with proved (in 3), clinically definite (in 32), early probable (in 13) and suspected (in 2) cases of multiple sclerosis were studied. Certain clinical characteristics in Thai patients are noteworthy, namely, a higher female to male ratio (4:1), a higher rate of optic nerve involvement (76%), and lower rate of brain stem involvement (30%) and cerebellar involvement (10%) during the course of illness in contrast to those of Western series. Painful tonic seizure was a prominent feature in Thai patients with multiple sclerosis (22/50 or 44%). Thirty out of 50 patients could be traced. Ten patients had died (33%) from the disease after 1-21 years with a mean of 8.08 years. Twenty patients (66%) were still alive. The follow-up period was 2-12 years with an average of 6.65 years. Among the twenty, 3 were bed-ridden, 3 were chair-bound and 5 had restricted activities. Nine patients (30%) were still working fully. PMID- 7869005 TI - Post-cesarean section urinary tract infection: a comparison between intermittent and indwelling catheterization. AB - Catheterization, which is widely accepted as an important factor to urinary tract infection, is routinely done during cesarean section. This randomized study was conducted to compare the incidence of urinary tract infection between patients who underwent cesarean section using intermittent catheterization and indwelling catheterization, at the Department of Obstetrics and Gynecology, Ramathibodi Hospital from August 1991 to December 1991. Sixteen of 51 patients (31.4%) of the intermittent group and 9 of 47 patients (19.1%) of the indwelling group developed urinary tract infection. The difference was not statistically significant. Of the patients in the intermittent group 39.2 per cent were found to have postoperative urinary retention requiring recatheterization, whereas all cases in the indwelling group could void after its removal. Klebsiella pneumoniae was the commonest isolated organism. Indwelling catheterization was concluded to be the favourable method. PMID- 7869006 TI - A second outbreak of cholera in the home for mentally handicapped, Nonthaburi. AB - A second outbreak of cholera, due to the Ogawa strain, occurred in the home for Mentally Handicapped Children in Nonthaburi between July 29 and August 9, 1992. An outbreak of cholera due to the Inaba strain was reported in the same institution and season tin 1987. In 1992, the clinical attack rate was 8 per cent of 440 children; there were two deaths. Bath water was contaminated with Vibrio cholerae O1 E1 Tor Ogawa, the same strain as was isolated from the ill children. Chlorination of the water supply, obtained from an underground well, was insufficient. The water supply needs further investigation, and the sanitary conditions in the institutions should be improved. PMID- 7869007 TI - Treatment of cryptococcal meningitis with combination itraconazole and flucytosine. AB - The results of an open study of the efficacy of itraconazole and flucytosine in 10 patients with cryptococcal meningitis are reported. The outcome revealed eight responding cases (cure in 4 cases and improvement in 4 cases), and two failure cases. One patient had a relapse which responded to amphotericin B and flucytosine. No toxicity was observed. PMID- 7869008 TI - The prevalence of HIV infection among mentally ill offenders in Thailand. AB - The study was made at Nitichitawej Hospital in 1988 to find the prevalence among mentally ill offenders whom had detained there. The total of 325 cases were investigated by gel agglutination and confirmed by W-B analysis. A total of 81.5 per cent were mentally ill and the 1.85 per cent of these were HIV infected. Among the seropositive HIV, the two cases were Schizophrenia and the four cases were drug addicted. PMID- 7869009 TI - Dental management in irradiated head and neck cancers. AB - Seventy three head and neck cancer patients were radiated between 1987 and 1993 at the Faculty of Medicine, Ramathibodi Hospital, Mahidol University. The incidence of dental extraction was much decreased after fluoride treatment regardless of the method of treatment with 54.8 per cent of the patients followed up for more than 36 months. There was no significant difference of the dental status between application of fluoride gel, fluoride solution month rinse and combination of gel and solution. The incidence of dental extraction decreased to 6.9-22.7 per cent but dental filling increased to 54.5-68.2 per cent. We would like to conclude that continuing dental care with daily home fluoride month rinse and 3-6 months follow-up by the dentists will be the proper way to prevent radiation dental caries. PMID- 7869010 TI - Significance of ascitic fluid white blood cells, pH, lactate, and other chemistry in immediate diagnosis of spontaneous bacterial peritonitis. AB - From 1989 to 1991, 68 cirrhotic patients, 47 with uninfected ascites and 21 with SBP were studied for the significance of ascitic fluid pH, lactate, PMN count and other chemistry for immediate diagnosis of SBP. It was revealed that ascitic fluid PMN count if over 500 per mm3, the increased lactate, or decreased glucose level, strongly supported the diagnosis of SBP. In cases of suspecting SBP but with low PMN count the ascitic values of lactate, glucose and pH will guide the diagnosis. If the ascitic lactate plus glucose, or lactate plus pH are above the cut off levels (lactate > 25 mg/dl; glucose < 60 mg/dl and pH < 7.35) the diagnosis is strongly suggestive. The ascitic fluid pH and A-AF pH gradient were not of diagnostic value due to instability of pH after tapping. For other chemistry in the ascitic fluid, there was a slight increase in ADA level in SBP, but for glucose, protein and glutamine levels, there was no difference among the groups with and without SBP. PMID- 7869011 TI - Radiology of retroperitoneal cystic teratoma in adult: a case report. AB - Retroperitoneal teratoma is a rare tumour in adults. A case is reported in which the radiologic pattern led to preoperative diagnosis of cystic teratoma, indicating surgical removal, which benefited the patient. However, size, calcification, and demonstration of cystic or solid components, are not predictive of benign tumour behaviour. Definite diagnosis was made possible by histopathology. PMID- 7869012 TI - Humeral lengthening: a report of 2 cases. AB - Surgical lengthening of the humerus can be performed safely if the surgeon takes care to avoid and prevent complications which may occur. The technic depends on the surgeon's experience, but preservation of the periosteal and endoosteal blood supply should be of concern. The amount of lengthening less than 10 cm is safe. Bone graft is not necessary when Ilizarov's concept is used. PMID- 7869013 TI - Efficacy and acceptability of perindopril in essential hypertension. AB - The clinical efficacy and acceptability of once-daily perindopril (4 to 8 mg) monotherapy and in combination with hydrochlorothiazide (50 mg/day) was studied in mild to moderate stable essential hypertensive patients in 4 centres in Thailand. After 2-4 weeks of placebo run-in period, patients received active treatment for 3 months starting with 4 mg perindopril once daily. Dose titration was at second and third month of active treatment if the supine DBP was > 90 mmHg. The dose was doubled and if necessary, 50 mg/day hydrochlorothiazide was added in the last month. The results in 95 patients showed that the mean reduction in supine SBP/DBP at 1, 2 and 3 months of treatment was 10.3/8.0, 13.2/8.7 and 19.1/13.7 mmHg respectively. At the end of the study, 80 per cent of the patients showed normalisation of the supine diastolic blood pressure (supine DBP < or = 90 mmHg) with 30 per cent receiving combined therapy of perindopril and hydrochlorothiazide. There was no significant change in routine haematology or serum biochemistry except for slight increase of potassium levels in patients receiving 8 mg perindopril monotherapy. The incidence of side effects and withdrawal from treatment were quite low. Cough was the major side effect reported comprising 13.6 per cent with only 1 case withdrawn. The study confirms the previous studies that perindopril had satisfactory antihypertensive efficacy and acceptability profiles. PMID- 7869014 TI - Seroprevalence of HIV antibodies and risk factors in healthy young males from upper north Thailand. AB - In the Spring of 1991 a random sample of young men from Upper Northern Thailand (mean age = 21 years) was interviewed by trained medical students from Chiang Mai University, serum samples were obtained and analyzed for prevalence of HIV-1 antibodies and for syphilis, and risk factors for HIV infection were assessed. It was found that Commercial Sex Workers (CSW) were the principal risk factor, that consistent condom use is rare, and the rates of HIV infection are rising rapidly. Sociodemographic background, homosexual behavior, drug use, and history of STD's were found to be not significant risk factors. The conclusions are that the education campaigns should be intensified to reduce the frequency of contact with CSW and to encourage consistent use of condoms. PMID- 7869015 TI - Monospecific antivenin therapy in Russell's viper bite. AB - Venom antigenemia was detected in 24 out of 30 Russell's viper bites. Those who suffered clinical bleeding (N = 14) had higher venom antigenemia than those who did not. The mean value of the amount of monospecific antivenin correcting blood incoagulability was 165 +/- 59.3 ml. Consequently, the recommended treatment is 60 ml of antivenin being administered intravenously at 6-hour intervals until blood coagulability is restored. There were no serious complications after antivenin administration. Renal complication (3 cases) was the major problem following this snake bite. One patient with clinical diagnosis of central nervous system bleeding died on admission. PMID- 7869016 TI - Susceptibility patterns of clinical bacterial isolates in nineteen selected hospitals in Thailand. AB - Susceptibility patterns of 3,115 clinical isolates obtained from blood, urine, sputum and pus in 19 hospitals located in each part of Thailand, were studied using ampicillin, ampicillin plus sulbactam, piperacillin, gentamicin, amikacin, cefazolin, cefuroxime, cefotaxime, ceftazidime, ofloxacin and imipenem. E.coli, S.aureus, P. aeruginosa, Klebsiella spp., Acinetobacter spp., Proteus spp. and Salmonella spp., were the seven most common isolates and accounted for 28.3, 15.3, 14.6, 14.5, 5.2, 3.3 and 3.3 per cent of total isolates respectively. Susceptibility percentages of common bacterial isolates from blood to third generation cephalosporins, amikacin, ofloxacin and imipenem were satisfactory and higher than those of clinical isolates from other specimens. As expected, nosocomial strains were more resistant than community-acquired strains. Isolates from government hospitals were more resistant to gentamicin and amikacin but more susceptible to ampicillin compared with those from private hospitals. Susceptibility to imipenem among isolates from private hospitals was less but did not reach statistical significance. PMID- 7869017 TI - Radiation treatment of retinoblastoma: experience in the past two decades. AB - This series of 193 patients represents the results in management of retinoblastoma. In cases treated 15 years ago when definitive radiotherapy and fat soluble chemotherapy were not utilized, the results of the treatment were very disappointing. The outcome was more promising after October 1985. Even if all the patients were in the advanced stages, we had a promising outcome, so effective modality of treatment is the most important prognostic factor. The other factors that influence the prognosis include the time for initial treatment, the time for starting the postoperative radiation and the efficiency of the radiation treatment. The follow-up period of 2 years after treatment is adequate to predict the outcome. PMID- 7869018 TI - Changes in urinary chemical composition in healthy volunteers after consuming roselle (Hibiscus sabdariffa Linn.) juice. AB - The objective of this study was to evaluate the changes of urine in normal subjects after consuming roselle juice in different concentrations and durations which may help the treatment and prevention of renal stone disease. Thirty-six healthy men participated in the study, in which urinalysis, urine electrolytes and indices for measurements of concentration of urine were determined before, during and after roselle juice consumption. The urine after consumption of roselle juice showed a decrease of creatinine, uric acid, citrate, tartrate, calcium, sodium, potassium and phosphate but not oxalate in urinary excretion. The CPR values of the majority of each individual increased and means PI values decreased in phase 1. Contrarily, the CPR values of the majority of volunteers decreased and means PI values increased in phase 2. In conclusion a low dose of roselle juice (16 g/day) caused more significant decrease in salt output in the urine than a high dose (24 g/day). The urinary changes were similar to the observations on villagers with and without stones in northeastern Thailand. PMID- 7869019 TI - Disseminated cryptococcosis presenting as molluscum-like lesions in three male patients with acquired immunodeficiency syndrome. AB - Cryptococcosis is an opportunistic infection caused by a ubiquitous encapsulated yeast, Cryptococcus neoformans. The pulmonary infection is primary site and most frequently self-limited and may be asymptomatic. The most common recognized site of disseminated cryptococcosis is the central nervous system. The cutaneous cryptococcosis is rare and nonspecific. More recently, in patients with AIDS, some cases of cutaneous cryptococcosis resembling molluscum contagiosum have been described and occasionally appeared before systemic signs and symptoms. To our knowledge, this has not previously been reported in Thailand. This is a report of 3 males with acquired immunodeficiency syndrome who developed disseminated cryptococcosis with cutaneous lesions resembling molluscum contagiosum. Skin findings in disseminated cryptococcosis indicate a poor prognosis, however, earlier recognition and treatment would improve survival. PMID- 7869020 TI - Polyglandular autoimmune (PGA) syndromes: report of three cases and review of the literature. AB - Polyglandular autoimmune (PGA) syndrome is caused by autoimmune process in multiple endocrine glands. This usually results in endocrine gland hypofunction, except for the thyroid gland, in which both hyper or hypofunction may occur. The syndrome can be classified into two types, type I and type II, each with distinct clinical characteristics. We report three cases of PGA syndromes. The first patient had type I PGA syndrome, characterized by hypoparathyrodism, primary adrenal insufficiency and primary ovarian failure. She also had chronic mucocutaneous candidiasis, which is the distinct feature in this syndrome. The second patient had type II PGA syndrome, with primary adrenal insufficiency, Hashimoto's thyroiditis and primary ovarian failure. She also had widespread vitilgo. The last patient also had type II PGA syndrome. She had insulin dependent diabetes mellitus, Graves' disease and alopecia areata. PMID- 7869021 TI - Extracorporeal membrane oxygenation for postoperative cardiac support in Ebstein's anomaly: a case report. AB - A case of successfully prolonged ECMO for post-operative cardiac support was reported on and a review of literatures with regard to the various aspects of this condition was presented. We hope that prolonged ECMO will become a valuable tool in the armamentarium of the surgeon treating postcardiotomy circulatory failure. PMID- 7869022 TI - Differential vocalization in budgerigars: towards an experimental analysis of naming. AB - In Experiment 1, 3 budgerigars (Melopsittacus undulatus) were trained with food reinforcement to make low- or high-frequency calls in response to different color stimuli, C1 and C2 (a color-naming task), using a gradual response differentiation procedure and an automatic call-recognition system. Thus, a call within a certain frequency band was reinforced in the presence of C1 ("C1 call"), and a call within a different band was reinforced in the presence of C2 ("C2 call"). In Experiment 2, all 3 budgerigars were trained in a form-to-color matching-to-sample task, alternating trial by trial with either the color-naming task (2 birds) or an identity color matching-to-sample task (1 bird). Sample stimuli for the new matching-to-sample task were forms (F1 or F2) and comparisons were the same two colors (C1 and C2). Given Sample F1 or F2, birds had to make a call to produce Comparison Pair C1 and C2. With F1 as the sample, a peck on C1 was reinforced; with F2 as the sample, a peck on C2 was reinforced. Although no particular call was specified in the presence of F1 and F2, 2 birds made the C1 call in the presence of F1 and the C2 call in the presence of F2. In Experiment 3, the bird that failed to match form and color calls in Experiment 2 and another bird were first trained in a color-to-form matching-to-sample task: C1 to F3 and C2 to F4. In this task, to produce the comparison pair of forms, a high call (or low for the other bird) was required in the presence of C1, and a low call (or high) was required in the presence of C2. Both birds were then trained with an identity matching-to-sample task in which sample and comparison stimuli were the same two forms, F3 and F4. Trials on the identity task alternated with the color to-form trials. Although no particular call was required in the presence of Samples F3 and F4, both birds came to make the C1 call in the presence of F3 and the C2 call in the presence of F4. Our technique promises to be useful for the study of emergent vocal relations in budgerigars and other animals. PMID- 7869024 TI - Effects of a variable-ratio conditioning history on sensitivity to fixed-interval contingencies in rats. AB - We investigated the possibility that human-like fixed-interval performances would appear in rats given a variable-ratio history (Wanchisen, Tatham, & Mooney, 1989). Nine rats were trained under single or compound variable-ratio schedules and then under a fixed-interval 30-s schedule. The histories produced high fixed interval rates that declined slowly over 90 sessions; differences as a function of the particular history were absent. Nine control animals given only fixed interval training responded at lower levels initially, but rates increased with training. Despite differences in absolute rates, rates within the intervals and postreinforcement pauses indicated equivalent development of the accelerated response patterns suggestive of sensitivity to fixed-interval contingencies. The finding that the histories elevated rates without retarding development of differentiated patterns suggests that the effective response unit was a burst of several lever presses and that the fixed-interval contingencies acted on these units in the same way as for single responses. Regardless of history, the rats did not manifest the persistent, undifferentiated responding reported for humans under comparable schedules. We concluded that the shortcomings of animal models of human fixed-interval performances cannot be easily remedied by including a variable-ratio conditioning history within the model. PMID- 7869023 TI - The effects of cocaine on behavior maintained by timeout from avoidance. AB - Rats were trained on concurrent schedules under which responses on one lever postponed shock (avoidance) and responses on the other lever produced brief (2 min) periods of signaled timeout from avoidance. For 6 rats, timeout from avoidance was programmed on a variable-interval 45-s schedule that generally resulted in rates that were lower than those on the avoidance lever. For another 6 rats, timeout was arranged on a variable-ratio 15 schedule that produced higher baseline rates. Cocaine (3 to 40 mg/kg) produced large, dose-dependent increases in behavior maintained by timeout in both groups of rats. Avoidance responding was also generally increased by cocaine, but the increases were of lesser magnitude. Increases in response rates were seen across a broad range of doses on behavior maintained by either interval or ratio schedules, an outcome that was unexpected on the basis of most studies of cocaine on food-maintained behavior. These results were similar to those of previous studies of the effects of amphetamine on behavior maintained by timeout from avoidance and suggest that stimulant drugs affect behavior maintained under a shock-postponement schedule differently than they affect behavior maintained by timeout from avoidance. PMID- 7869025 TI - The B cell antigen receptor of class IgD induces a stronger and more prolonged protein tyrosine phosphorylation than that of class IgM. AB - Most mature B lymphocytes coexpress two classes of antigen receptor, immunoglobulin (Ig)M and IgD. The differences in the signal transduction from the two receptors are still a matter of controversy. We have analyzed B cell lines expressing IgM or IgD antigen receptors with the same antigen specificity. Cross linking of these receptors with either antigen, or class-specific antibodies, results in the activation of protein tyrosine kinases and the phosphorylation of the same substrate proteins. The kinetic and the intensity of phosphorylation, however, was quite different between the two receptors when they were cross linked by antigen. In membrane IgM-expressing cells, the substrate phosphorylation reached a maximum after 1 minute and diminished after 60 minutes whereas, in the membrane IgD-expressing cells, the substrate phosphorylation increased further over time, reached its maximum at 60 minutes, and persisted longer than 240 minutes after exposure to antigen. As a result, the intensity of protein tyrosine phosphorylation induced by cross-linking of membrane IgD was stronger than that induced by membrane IgM. Studies of chimeric receptors demonstrate that only the membrane-proximal C domain and/or the transmembrane part of membrane-bound IgD molecule is required for the long-lasting substrate phosphorylation. Together, these data suggest that the signal emission from the two receptors is controlled differently. PMID- 7869027 TI - Synergistic roles of granzymes A and B in mediating target cell death by rat basophilic leukemia mast cell tumors also expressing cytolysin/perforin. AB - We have studied the cytotoxic activity of rat basophilic leukemia (RBL) cells transfected with cDNAs for the cytotoxic T lymphocyte (CTL) granule components, cytolysin (perforin), granzyme A, and granzyme B. With red cell targets, cytolysin expression conferred potent hemolytic activity, which was not influenced by coexpression of granzymes. With tumor targets, RBL cells expressing cytolysin alone were weakly cytotoxic, but both cytolytic and nucleolytic activity were enhanced by coexpression of granzyme B. RBL cells expressing all three CTL granule components showed still higher cytotoxic activities, with apoptotic target death. Analysis of the cytotoxic activity of individual transfectant clones showed that cytolytic and nucleolytic activity correlated with granzyme expression but was independent of cytolysin expression within the range examined. A synergism between granzymes A and B was apparent when the triple transfectant was compared with RBL cells expressing cytolysin and one granzyme. These data implicate granzymes as the major mediators of tumor target damage by cytotoxic lymphocytes. PMID- 7869026 TI - Activation of monocyte effector genes and STAT family transcription factors by inflammatory synovial fluid is independent of interferon gamma. AB - Activated monocytes play an important role in the pathogenesis of inflammatory arthritis. Blood monocytes which enter the inflamed joint become activated upon adherence to extracellular matrix and exposure to a complex inflammatory environment. We have analyzed the mechanism of monocyte activation by soluble factors present in inflammatory synovial fluid (SF). Greater than 75% of inflammatory SFs tested (a total of 22 fluids to date) increased cell surface expression and dramatically increased mRNA levels of monocyte activation markers Fc gamma RI, Fc gamma RIII, and HLA-DRA. This induction was not triggered by adherence, a known activating stimulus, and several lines of evidence showed that induction was not dependent upon interferon gamma (IFN-gamma). Induction was not prevented by neutralizing anti-IFN-gamma antibodies and IFN-gamma was not detected in the SFs using a sensitive enzyme-linked immunosorbent assay. The SFs also were not able to activate the IFN-gamma-activated transcription factor Stat1, thus providing further support for the absence of IFN-gamma. SFs did activate a related signal transducer and activator of transcription (STAT) family factor, termed Stat-SF, which bound specifically to the IFN-gamma response region (GRR), a well-characterized transcription element in the Fc gamma RI promoter. Based upon DNA-binding specificity and mobilities in gel shift assays, and reactivity with specific antisera, Stat-SF likely contains Stat3, or a closely related STAT family member. Neutralization of interleukin 6, a cytokine present in SFs which is known to activate Stat3, abolished the activation of Stat-SF and inhibited the induction of Fc gamma RI expression by SFs. These results demonstrate the activation of monocytes by inflammatory SF and suggest that monocyte activation at an inflammatory site may occur in the absence of IFN-gamma through the triggering of signal transduction pathways that activate STAT transcription factors. PMID- 7869028 TI - lambda 5, but not mu, is required for B cell maturation in a unique gamma 2b transgenic mouse line. AB - gamma 2b transgenic mice have a severe B cell defect, apparently caused by strong feedback inhibition of endogenous H-gene rearrangement coupled with an inability of gamma 2b to provide the survival/maturation functions of mu. A unique gamma 2b transgenic line, named the C line, was found to permit B cell development. When the C line is crossed with a mu-membrane knockout line, gamma 2b+ B cells develop in the homozygous knockout. In contrast, a transgenic line representative of all the other gamma 2b lines is completely B cell deficient when mu-mem is deleted. Strikingly, the C phenotype is dominant in C x other gamma 2b transgenic line crosses. There is no evidence for higher gamma 2b transgene expression or other position effects on the transgene in the C mouse. The sequences of the three gamma 2b transgene copies in the C line are identical to that of the original transgene. These results have led to the conclusion that in the C line the transgene integration constitutively induces a gene whose expression can replace mu. To more clearly delineate the stage at which the altered phenotype of the C line is expressed, C mice were crossed onto a lambda 5 knockout background. In the absence of lambda 5, the C line produces no B cells. Since it was also found that gamma 2b can associate with the surrogate light chain (sL; lambda 5/Vpre-B), the crosses between C line gamma 2b mice and lambda 5 knockout mice suggest that gamma 2b/sL is required for B cell maturation in this mouse line. Thus, gamma 2b alone is unable to replace mu for pre-B cell survival/maturation; however, in combination with an unknown factor and the sL, gamma 2b can provide these nurturing functions. PMID- 7869029 TI - Nerve growth factor triggers microfilament assembly and paxillin phosphorylation in human B lymphocytes. AB - Increasing evidence suggests that the nervous system is involved in allergic inflammation. One of the potential regulatory molecules of the neuroimmune system is nerve growth factor (NGF). Recent studies from our group demonstrated the presence of a functional NGF receptor (NGFR) on human B lymphocytes. Moreover, we showed that gp140trk tyrosine kinase, which serves as an NGFR, was involved in transduction of early signaling events in human B lymphocytes. The mechanisms by which NGF initiates the signaling cascade and the link between the neuroimmune systems are unknown. We have focused on the role of the cytoskeleton as a possible mediator for transduction of signals induced by NGF. Polymerized actin (F-actin) content was determined by fluorescent staining and immunoblotting with antiactin antibody. Addition of NGF caused a time- and concentration-dependent increase in F-actin content, and maximum effects were noted after 1 min. These increases in F-actin content and NGF-induced thymidine incorporation could be blocked by incubating the cells with cytochalasin D and botulinum C2 toxin before the addition of NGF. Incubation of human B lymphocytes with 10 nM K252a, an inhibitor of Trk kinase, decreased NGF-induced microfilament assembly by 75%. In immunoprecipitation experiments, addition of NGF to B cells induced a rapid increase in the tyrosine phosphorylation of paxillin, one of a group of focal adhesion proteins involved in linking actin filaments to the plasma membrane. Coimmunoprecipitation studies demonstrated the association between gp140trk kinase and paxillin. Together, these observations suggest that actin assembly is involved in NGF signaling in human B cells, and that paxillin may be essential in this pathway after phosphorylation by gp140trk kinase. PMID- 7869030 TI - Interleukin 4 production by CD4+ T cells from allergic individuals is modulated by antigen concentration and antigen-presenting cell type. AB - We have previously shown that CD4+ T cells from allergic individuals are predisposed to produce interleukin (IL)-4 in response to allergens, and that allergen immunotherapy greatly reduced IL-4 production in an allergen-specific fashion. The mechanism that results in the reduction of IL-4 synthesis in treated individuals is unknown, but because clinical improvement during immunotherapy is associated with the administration of the highest doses of allergen, we hypothesized that high concentration of allergen results in the downregulation of IL-4 synthesis in CD4+ T cells. In this report, we demonstrated that CD4+ T cells from allergic donors produced high levels of IL-4 when stimulated with low concentrations of allergen (0.003-0.01 micrograms/ml), particularly when B cell enriched populations presented the antigen. In contrast, the same responding CD4+ T cell population produced little IL-4 when stimulated with high concentrations of allergen (10-30 micrograms/ml), especially when monocytes were used as antigen presenting cells (APC). The quantity of IL-4 produced was also found to be inversely related to the extent of proliferation of the CD4+ T cells in response to allergen/antigen; maximal proliferation of CD4+ T cells occurred in response to high concentrations of antigen when IL-4 production was minimal. Antigen presentation by B cell-enriched populations, instead of monocytes, induced less CD4+ T cell proliferation, but induced much greater IL-4 synthesis. Moreover, the addition of increasing numbers of APC (either B cells or monocytes) to cultures containing a constant number of responder T cells resulted in increased T cell proliferation and decreased IL-4 production. These results indicate that the circumstances under which memory T cells are activated, as well as the strength of the proliferative signal to T cells, greatly affect the quantity of IL-4 produced. Thus, our observations that the cytokine profile of allergen-specific memory CD4+ T cells can indeed be modulated by the antigen dose and APC type suggest that methods that preferentially enhance allergen uptake by monocytes and that enhance T cell proliferation will improve the clinical efficacy of immunotherapy in the treatment of allergic disease. PMID- 7869031 TI - Ligation of CD38 suppresses human B lymphopoiesis. AB - CD38 is a transmembrane glycoprotein expressed in many cell types, including lymphoid progenitors and activated lymphocytes. High levels of CD38 expression on immature lymphoid cells suggest its role in the regulation of cell growth and differentiation, but there is no evidence demonstrating a functional activity of CD38 on these cells. We used stroma-supported cultures of B cell progenitors and anti-CD38 monoclonal antibodies (T16 and IB4) to study CD38 function. In cultures of normal bone marrow CD19+ cells (n = 5), addition of anti-CD38 markedly reduced the number of cells recovered after 7 d. Cell loss was greatest among CD19+ sIg- B cell progenitors (mean cell recovery +/- SD = 7.2 +/- 11.7% of recovery in control cultures) and extended to CD19+CD34+ B cells (the most immature subset; 7.6 +/- 2.2%). In contrast, CD38 ligation did not substantially affect cell numbers in cultures of normal peripheral blood or tonsillar B cells. In stroma supported cultures of 22 B-lineage acute lymphoblastic leukemia cases, anti-CD38 suppressed recovery of CD19+ sIg- leukemic cells. CD38 ligation also suppressed the growth of immature lymphoid cell lines cultured on stroma and, in some cases, in the presence of stroma-derived cytokines (interleukin [IL] 7, IL-3, and/or stem cell factor), but did not inhibit growth in stroma- or cytokine-free cultures. DNA content and DNA fragmentation studies showed that CD38 ligation of stroma-supported cells resulted in both inhibition of DNA synthesis and induction of apoptosis. It is known that CD38 catalyzes nicotinamide adenine dinucleotide (NAD+) hydrolysis into cyclic ADP-ribose (cADPR) and ADPR. However, no changes in NAD+ hydrolysis or cADPR and ADPR production after CD38 ligation were found by high-performance liquid chromatography; addition of NAD+, ADPR, or cADPR to cultures of lymphoid progenitors did not offset the inhibitory effects of anti CD38. Thus, anti-CD38 does not suppress B lymphopoiesis by altering the enzymatic function of the molecule. In conclusion, these data show that CD38 ligation inhibits the growth of immature B lymphoid cells in the bone marrow microenvironment, and suggest that CD38 interaction with a putative ligand represents a novel regulatory mechanism of B lymphopoiesis. PMID- 7869032 TI - Peptide influences the folding and intracellular transport of free major histocompatibility complex class I heavy chains. AB - Class I major histocompatibility complex molecules require both beta 2 microglobulin (beta 2m) and peptide for efficient intracellular transport. With the exception of H-2Db and Ld, class I heavy chains have not been detectable at the surface of cells lacking beta 2m. We show that properly conformed class I heavy chains can be detected in a terminally glycosylated form indicative of cell surface expression in H-2b, H-2d, and H-2s beta 2m-/- concanavalin A (Con A) stimulated splenocytes incubated at reduced temperature. Furthermore, we demonstrate the presence of Kb molecules at the surface of beta 2m-/- cells cultured at 37 degrees C. The mode of assembly of class I molecules encompasses two major pathways: binding of peptide to preformed "empty" heterodimers, and binding of peptide to free heavy chains, followed by recruitment of beta 2m. In support of the existence of the latter pathway, we provide evidence for a role of peptide in intracellular transport of free class I heavy chains, through analysis of Con A-stimulated splenocytes from transporter associated with antigen processing 1 (TAP1)-/-, beta 2m-/-, and double-mutant TAP1/beta 2m-/- mice. PMID- 7869033 TI - Antibody-mediated autoimmune myocarditis depends on genetically determined target organ sensitivity. AB - Injury to cardiac myocytes often leads to the production of anti-myosin antibodies. While these antibodies are a marker of myocardial injury, their contribution to pathogenesis in diseases such as autoimmune myocarditis or rheumatic fever is much less clear. We demonstrate in this report that monoclonal anti-myosin antibodies can mediate myocarditis in a susceptible mouse strain. Additionally, we show disease susceptibility depends on the presence of myosin or a myosin-like molecule in cardiac extracellular matrix. This study demonstrates that susceptibility to autoimmune heart disease depends not only on the activation of self-reactive lymphocytes but also on genetically determined target organ sensitivity to autoantibodies. PMID- 7869034 TI - Role of Rel-related factors in control of c-myc gene transcription in receptor mediated apoptosis of the murine B cell WEHI 231 line. AB - Treatment of immature murine B lymphocytes with an antiserum against their surface immunoglobulin (sIg)M results in cell death via apoptosis. The WEHI 231 B cell line (IgM, kappa) has been used extensively as a model for this anti-Ig receptor-mediated apoptosis. Anti-sIg treatment of WEHI 231 cells causes an early, transient increase in the levels of c-myc messenger RNA and gene transcription, followed by a rapid decline below control values. Given the evidence for a role of the c-myc gene in promoting apoptosis, we have characterized the nature and kinetics of changes in the binding of Rel-related factors, which modulate c-myc promoter activity. In exponentially growing WEHI 231 cells, multiple Rel-related binding activities were detectable. The major binding species was identified as p50/c-Rel heterodimers; only minor amounts of nuclear factor kappa B (NF-kappa B) (p50/p65) were detectable. Cotransfection of an inhibitor of NF-kappa B (I kappa B)-alpha expression vector reduced c-myc promoter/upstream/exon1-CAT reporter construct activity, indicating the role of Rel factor binding in c-myc basal expression in these cells. Treatment with anti sIg resulted in a rapid transient increase in the rate of c-myc gene transcription and in the binding of Rel factors. At later times, formation of p50 homodimer complexes occurred. In cotransfection analysis, p65 and c-Rel expression potently and modestly transactivated the c-myc promoter, respectively, whereas, overexpression of the p50 subunit caused a significant drop in its activity. The role of activation of Rel-family binding was demonstrated directly upon addition of the antioxidant pyrrolidinedithiocarbamate, which inhibited the anti-sIg-mediated activation of the endogenous c-myc gene. Similarly, induction after anti-sIg treatment of a transfected c-myc promoter was abrogated upon cotransfection of an I kappa B-alpha expression vector. These results implicate the Rel-family in Ig receptor-mediated signals controlling the activation of c myc gene transcription in WEHI 231 cells, and suggest a role for this family in apoptosis of this line, which is mediated through a c-myc signaling pathway. PMID- 7869035 TI - Development of CD4+CD8+ thymocytes in RAG-deficient mice through a T cell receptor beta chain-independent pathway. AB - Antigen-binding diversity is generated by site-specific V(D)J recombination of the T cell receptor (TCR) and immunoglobulin loci in lymphocyte precursors. Coordinate expression of two structurally distinct recombinase activating genes, RAG-1 and RAG-2, is necessary for activation of site-specific V(D)J recombination. In mice bearing targeted disruptions of either the RAG-1 or RAG-2 genes, T and B lymphocyte development is arrested at the CD4-8- double negative (DN) thymocyte or B220+/CD43+ pro-B cell stage. Development of CD4+CD8+ double positive (DP) thymocytes is restored by expression of a functionally rearranged TCR beta transgene, suggesting that TCR beta expression is critical for this developmental transition. We have found that treatment of adult or newborn RAG deficient mice with a single sublethal dose of gamma-irradiation rescues the DN to DP transition in early thymocytes, and this is accompanied by a dramatic increase in thymus cellularity. In contrast to the observed induction of thymocyte maturation, there was no phenotypic or functional evidence of coincident B lymphocyte development in irradiated RAG-deficient mice. Interestingly, maturation of DP thymocytes occurred without expression of TCR beta protein in the cytoplasm or on the cell surface. These results suggest an in vivo pathway for DP thymocyte development which is TCR beta chain independent. PMID- 7869036 TI - A metalloprotease inhibitor blocks shedding of the 80-kD TNF receptor and TNF processing in T lymphocytes. AB - TNF is synthesized as a 26-kD membrane-anchored precursor and is proteolytically processed at the cell surface to yield the mature secreted 17-kD polypeptide. The 80-kD tumor necrosis factor (TNF) receptor (TNFR80) is also proteolytically cleaved at the cell surface (shed), releasing a soluble ligand-binding receptor fragment. Since processing of TNF and TNFR80 occurs concurrently in activated T cells, we asked whether a common protease may be involved. Here, we present evidence that a recently described inhibitor of TNF processing N-(D,L-[2 (hydroxyaminocarbonyl)methyl]-4-methylpentanoyl)L- 3-(2'naphthyl)- alanyl-L alanine, 2-aminoethyl amide (TAPI) also blocks shedding of TNFR80, suggesting that these processes may be coordinately regulated during T cell activation. In addition, studies of murine fibroblasts transfected with human TNFR80, or a cytoplasmic deletion form of TNFR80, reveal that inhibition of TNFR80 shedding by TAPI is independent of receptor phosphorylation and does not require the receptor cytoplasmic domain. PMID- 7869037 TI - Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung. AB - Eotaxin is a member of the C-C family of chemokines and is related during antigen challenge in a guinea pig model of allergic airway inflammation (asthma). Consistent with its putative role in eosinophilic inflammation, eotaxin induces the selective infiltration of eosinophils when injected into the lung and skin. Using a guinea pig lung cDNA library, we have cloned full-length eotaxin cDNA. The cDNA encodes a protein of 96 amino acids, including a putative 23-amino acid hydrophobic leader sequence, followed by 73 amino acids composing the mature active eotaxin protein. The protein-coding region of this cDNA is 73, 71, 50, and 48% identical in nucleic acid sequence to those of human macrophage chemoattractant protein (MCP) 3, MCP-1, macrophage inflammatory protein (MIP) 1 alpha, and RANTES, respectively. Analysis of genomic DNA suggested that there is a single eotaxin gene in guinea pig which is apparently conserved in mice. High constitutive levels of eotaxin mRNA expression were observed in the lung, while the intestines, stomach, spleen, liver, heart, thymus, testes, and kidney expressed lower levels. To determine if eotaxin mRNA levels are elevated during allergen-induced eosinophilic airway inflammation, ovalbumin (OVA)-sensitized guinea pigs were challenged with aerosolized antigen. Compared with the lungs from saline-challenged animals, eotaxin mRNA levels increased sixfold within 3 h and returned to baseline by 6 h. Thus, eotaxin mRNA levels are increased in response to allergen challenge during the late phase response. The identification of constitutive eotaxin mRNA expression in multiple tissues suggests that in addition to regulating airway eosinophilia, eotaxin is likely to be involved in eosinophil recruitment into other tissues as well as in baseline tissue homing. PMID- 7869038 TI - Calcium/calmodulin-dependent protein kinase II downregulates both calcineurin and protein kinase C-mediated pathways for cytokine gene transcription in human T cells. AB - Engagement of the T cell receptor for antigen activates phospholipase C resulting in an increase in intracellular free calcium concentration ([Ca2+]i) and activation of protein kinase C (PKC). Increased [Ca2+]i activates Ca2+/calmodulin dependent kinases including the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaM-K II), as well as calcineurin, a type 2B protein phosphatase. Recent studies have identified calcineurin as a key enzyme for interleukin (IL)-2 and IL-4 promoter activation. However, the role of CaM-K II remains unknown. We have used mutants of these kinases and phosphatases (gamma B*CaM-K and delta CaM AI, respectively) to explore their relative role in cytokine gene transcription and their interactions with PKC-dependent signaling systems. gamma B*CaM-K and delta CaM-AI, known to exhibit constitutive Ca(2+)-independent activity, were cotransfected (alone or in combination) in Jurkat T cells with a plasmid containing the intact IL-2 promoter driving the expression of the chloramphenicol acetyltransferase reporter gene. Cotransfection of gamma B*CaM-K with the IL-2 promoter construct downregulated its transcription in response to stimulation with ionomycin and phorbol myristate acetate (PMA). The inhibitory effect of CaM K II on IL-2 promoter was associated with decreased transcription of its AP-1 and NF-AT transactivating pathways. Under the same conditions, delta CaM-AI superinduced IL-2 promoter activity (approximately twofold increase). When both mutants were used in combination, gamma B*CaM-K inhibited the induction of the IL 2 promoter by delta CaM-AI. Similar results were obtained when a construct containing the IL-4 promoter also was used. gamma B*CaM-K also downregulated the activation of AP-1 in response to transfection with a constitutively active mutant of PKC or stimulation with PMA. These results suggest that CaM-K II may exert negative influences on cytokine gene transcription in human T cells, and provide preliminary evidence for negative cross-talk with the calcineurin- and PKC-dependent signaling systems. PMID- 7869040 TI - Virus-specific CD8+ cells can switch to interleukin 5 production and induce airway eosinophilia. AB - Virus infections of the lung are thought to predispose individuals to asthma, a disease characterized by eosinophil infiltration of the airways. CD8+ T cells are an important part of the host response to virus infection, however, they have no reported role in eosinophil recruitment. We developed a mouse model of virus peptide-stimulated CD8+ T cell immune responses in the lung. We found that bystander CD4+ T helper cell type 2 immune responses to ovalbumin switched the virus peptide-specific CD8+ T cells in the lung to interleukin (IL) 5 production. Furthermore, when such IL-5-producing CD8 T cells were challenged via the airways with virus peptide, a significant eosinophil infiltration was induced. In vitro studies indicated that IL-4 could switch the virus-specific CD8+ T cells to IL-5 production. These results could explain the link between virus infection and acute exacerbation of asthma and, perhaps more importantly, they indicate an IL-4 dependent mechanism that would impair CD8+ T cell responses and delay viral clearance from the host. PMID- 7869039 TI - Transgenic expression of interleukin 7 restores T cell populations in nude mice. AB - The thymic lesion of the nude mouse causes a profound block in T cell development. The failure of most T cells to mature in nude mice is likely to reflect a requirement for signals elaborated in the normal thymus. Interleukin 7 (IL-7), a lymphokine that is normally expressed in the thymus and has been implicated in T cell maturation, might be central to this process. To test this possibility, we introduced a transgene directing lymphoid expression of IL-7 into nude mice and found that it substantially alleviates the block in T cell maturation caused by the thymic defect. IL-7 transgenic nude mice have increased numbers of peripheral cells expressing the T cell marker Thy-1, the T cell antigen receptor complex, and the co-receptors CD4 and CD8. The IL-7 transgene also restores T cell-specific proliferation and activation responses to the peripheral cells of transgene-rescued nude mice. Such findings point toward a fundamental role for IL-7 in the thymic maturation of T cells. PMID- 7869041 TI - gamma/delta T lymphocytes express CD40 ligand and induce isotype switching in B lymphocytes. AB - T cells expressing gamma/delta T cell receptors home to epithelial tissue and may play a role in immunity to infectious agents and foreign antigens. In an effort to understand the role of gamma/delta T cells in directing B cell responses, we investigated the capacity of human gamma/delta T cells to express CD40 ligand (CD40L) and to drive immunoglobulin (Ig) isotype switching in B cells. A multiple step purification procedure resulted in the recovery of highly pure populations of peripheral blood CD4-CD8- gamma/delta T cells. Neither CD40L surface expression nor CD40L mRNA were detected in unstimulated gamma/delta T cells. Stimulation with phorbol ester and ionomycin induced CD40L mRNA and surface CD40L expression by gamma/delta T cells. Both the percentage of CD40L+ cells and the cell surface density of CD40L were significantly lower in gamma/delta T cells compared to unselected T cells. We further demonstrated that in the presence of neutralizing monoclonal antibody to interferon gamma (IFN-gamma), gamma/delta T cells could induce IgE synthesis in B cells, albeit to a lesser extent than unselected T cells. Furthermore, IgE synthesis driven by gamma/delta T cells was inhibited by monoclonal antibody to CD40L. These observations demonstrate that activated gamma/delta T cells express CD40L and can induce isotype switching in B cells. PMID- 7869042 TI - kappa+lambda+ dual receptor B cells are present in the human peripheral repertoire. AB - It is a common notion that mature B lymphocytes express either kappa or lambda light (L) chains, although the mechanism that leads to such isotypic exclusion is still debated. We have investigated the extent of L chain isotypic exclusion in normal human peripheral blood B lymphocytes. By three-color staining with anti CD19, anti-kappa, and anti-lambda antibodies we could estimate that 0.2-0.5% of peripheral blood B cells from healthy adults express both kappa and lambda on the cell surface. The kappa+lambda+ cells were sorted, immortalized by Epstein-Barr virus, and five independent clones were characterized in detail. All clones express both kappa and lambda on the cell surface and produce immunoglobulin M that contain both kappa and lambda chains in the same molecule, i.e., hybrid antibodies. Sequencing of the L chains revealed in three out of five clones evidence for somatic mutations. It is interesting to note that among a panel of single receptor B cell clones we identified two lambda+ clones that carried a productively rearranged kappa, which was inactivated by a stop codon generated by somatic mutation. These findings indicate that dual receptor B lymphocytes can be found among mature antigen-selected B cells and suggest that somatic mutation can contribute to increase the degree of isotypic exclusion by inactivating a passenger, nonselected L chain. PMID- 7869043 TI - T helper phenotype and genetic susceptibility in experimental Lyme disease. AB - Infection of inbred mice with Borrelia burgdorferi results in strain-specific variation in the severity of pathogen-induced arthritis: BALB/c mice develop only mild disease whereas C3H/HeJ mice develop severe arthritis. The immunologic basis for varying host susceptibility has yet to be defined. We modified experimental Lyme disease to facilitate measurement of antigen-specific cytokine production in resistant and susceptible mice. The analysis revealed highly polarized lymphokine patterns directly linked to differing disease outcomes. Among the inbred strains of mice challenged with B. burgdorferi, production of interleukin 4 (IL-4) correlated to resistance whereas production of interferon gamma (IFN-gamma) correlated to susceptibility. We also demonstrate that production of IL-4 or IFN gamma regulates the severity of arthritis after infection. Neutralization of IL-4 in resistant BALB/c mice resulted in more severe arthritis whereas neutralization of IFN-gamma in susceptible C3H/HeJ mice attenuated the severity of disease. These results suggest a primary relationship between T helper cell phenotype and the genetic basis for susceptibility to experimental Lyme borreliosis. PMID- 7869044 TI - Chemoattraction of human blood T lymphocytes by interleukin-15. AB - Recombinant interleukin (IL)-15, derived from a simian kidney epithelial cell line, is a chemoattractant for human blood T lymphocytes judged by its ability to increase the proportion of cells in polarized morphology, to stimulate invasion of collagen gels containing IL-15, and to increase the proportion of locomotor cells observed by time-lapse videorecording. The ability of lymphocytes to respond was partly, but not completely, inhibited by pretreatment with anti-IL-2 receptor beta-chain. The activity of IL-15 was completely abolished by preincubation with aIL-15 but unaffected by preincubation with aIL-2. No response of monocytes, neutrophils, or B lymphocytes to IL-15 was observed. PMID- 7869045 TI - The electron microscope enters the realm of the intact cell. PMID- 7869046 TI - Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. AB - Interleukin-10 (IL-10) is produced at a high level by B lymphocytes and monocytes of patients with systemic lupus erythematosus (SLE). In the present work, we analyzed whether this increased production of IL-10 contributed to the abnormal production of immunoglobulins (Ig) and of autoantibodies in SLE. The role of IL 10 was compared with that of IL-6, another cytokine suspected to play a role in these abnormalities. The spontaneous in vitro production of IgM, IgG, and IgA by peripheral blood mononuclear cells from SLE patients was weakly increased by recombinant IL (rIL)-6, but strongly by rIL-10. This production was not significantly affected by an anti-IL-6 mAb but was decreased by an anti-IL-10 mAb. We then tested the in vivo effect of these antibodies in severe combined immunodeficiency mice injected with PBMC from SLE patients. The anti-IL-6 mAb did not significantly affect the serum concentration of total human IgG and of anti double-stranded DNA IgG in the mice. In contrast, the anti-IL-10 mAb strongly inhibited the production of autoantibodies, and, to a lesser extent, that of total human IgG. These results indicate that the Ig production by SLE B lymphocytes is largely IL-10 dependent, and that the increased production of IL 10 by SLE B lymphocytes and monocytes may represent a critical mechanism in the emergence of the autoimmune manifestations of the disease. PMID- 7869047 TI - T cell and non-T cell compartments can independently determine resistance to Leishmania major. AB - In experimental murine cutaneous leishmaniasis caused by Leishmania major (Lm), the cellular determinants governing development of protective or exacerbative T cells are not well understood. We, therefore, attempted to determine the influence of T cell and non-T cell compartments on disease outcome. To this end, T cell chimeric mice were constructed using adult thymectomized lethally irradiated, bone marrow-reconstituted (ATXBM) animals of genetically resistant, C57BL/6, or susceptible, BALB/c, backgrounds. These hosts were engrafted with naive T cell populations from H-2-congenic susceptible, BALB.B6-H-2b, or resistant, C57BL/6.C-H-2d, animals, respectively. Chimeric mice were then infected with Lm, and disease outcome was monitored. BALB/c T cell chimeric mice, BALB/c ATXBM hosts given naive C57BL/6.C-H-2d T cells, resolved their infections as indicated by reductions in both lesion size and parasite numbers. Furthermore, the mice developed typical Th1 (interferon[IFN]-gamma hiinterleukin[IL]-4lo) cytokine patterns. In contrast, both sham chimeric, BALB/c ATXBM hosts given naive BALB/c T cells, and control irradiated euthymic mice succumbed to infection, producing Th2 profiles (IFN-gamma loIL-4hiIL-10hi). C57BL/6 T cell chimeras, C57BL/6 ATXBM hosts given naive BALB.B6-H-2b T cells, resolved their infections as did C57BL/6 sham chimeras and euthymic controls. Interestingly, whereas C57BL/6 control animals produced Th1 cytokines, chimeric animals progressed from Th0 (IFN-gamma hiIL-4hiIL-10hi) to Th2 (IFN-gamma loIL-4hiIL 10hi) cytokine profiles as cure ensued. Both reconstitution and chimeric status of all mice were confirmed by flow cytometry. In addition, T cell receptor V beta usage of Lm-specific blasts was determined. In all cases, V beta use was multiclonal, involving primarily V beta 2, 4, 6, 8.1, 8.2, 8.3, 10, and 14, with relative V beta frequencies differing between H-2b and H-2d animals. Most importantly, however, these differences did not segregate between cure and noncure outcomes. These findings indicate that: (a) genetic traits determining cure in Lm infection can direct disease outcome from both T cell and non-T cell compartments; (b) the presence of the curing genotype in only one compartment is sufficient to confer cure; (c) curing genotype T cells autonomously assume a Th1 cytokine profile-mediating cure; (d) noncuring genotype T cells can mediate cure in a curing environment, despite the onset of Th2 cytokine production; and lastly, (e) antigen specificity of responding T cells, as assessed by V beta T cell receptor diversity, is not a critical determinant of disease outcome. PMID- 7869048 TI - Human thymic epithelial cells express an endogenous lectin, galectin-1, which binds to core 2 O-glycans on thymocytes and T lymphoblastoid cells. AB - Thymic epithelial cells play a crucial role in the selection of developing thymocytes. Thymocyte-epithelial cell interactions involve a number of adhesion molecules, including members of the integrin and immunoglobulin superfamilies. We found that human thymic epithelial cells synthesize an endogenous lectin, galectin-1, which binds to oligosaccharide ligands on the surface of thymocytes and T lymphoblastoid cells. Binding of T lymphoblastoid cells to thymic epithelial cells was inhibited by antibody to galectin-1 on the epithelial cells, and by two antibodies, T305 and 2B11, that recognize carbohydrate epitopes on the T cell surface glycoproteins CD43 and CD45, respectively. T lymphoblastoid cells and thymocytes bound recombinant galectin-1, as demonstrated by flow cytometric analysis, and lectin binding was completely inhibited in the presence of lactose. The degree of galectin-1 binding to thymocytes correlated with the maturation stage of the cells, as immature thymocytes bound more galectin-1 than did mature thymocytes. Preferential binding of galectin-1 to immature thymocytes may result from regulated expression of preferred oligosaccharide ligands on those cells, since we found that the epitope recognized by the T305 antibody, the core 2 O glycan structure on CD43, was expressed on cortical, but not medullary cells. The level of expression of the UDP-GlcNAc:Gal beta 1,3GalNAc-R beta 1, 6GlcNAc transferase (core 2 beta 1, 6 GlcNAc transferase, or C2GnT), which creates the core 2 O-glycan structure, correlated with the glycosylation change between cortical and medullary cells. Expression of mRNA encoding the C2GnT was high in subcapsular and cortical thymocytes and low in medullary thymocytes, as demonstrated by in situ hybridization. These results suggest that galectin-1 participates in thymocyte-thymic epithelial cell interactions, and that this interaction may be regulated by expression of relevant oligosaccharide ligands on the thymocyte cell surface. PMID- 7869049 TI - Multi-colony stimulating activity of interleukin 5 (IL-5) on hematopoietic progenitors from transgenic mice that express IL-5 receptor alpha subunit constitutively. AB - The interleukin 3 (IL-3), IL-5, and granulocyte/macrophage colony-stimulating factor receptors consist of a cytokine-specific alpha subunit and the common beta subunit. Whereas IL-3 stimulates various lineages of hematopoietic cells, including multipotential progenitors, IL-5 acts mainly as an eosinophil lineage specific factor. To investigate whether the lineage specificity of IL-5 is due to restricted expression of the IL-5 receptor alpha subunit (IL-5R alpha), we generated transgenic mice that express the mouse IL-5R alpha constitutively by phosphoglycerate kinase promoter. The transgenic mouse expressed IL-5R alpha ubiquitously, and the bone marrow cells formed various types of colonies, including multi-lineage colonies, in response to IL-5. IL-5 also supported formation of both multi-lineage and blast cell colonies from dormant progenitors of the 5-fluorouracil-treated transgenic mice. The cells composing the blast cell colony gave rise to many colonies including multi-lineage colonies when they were replated in secondary culture containing either Il-5 or IL-3. There was no significant difference in replating efficiency or in types of secondary colonies between IL-5- and IL-3-stimulated cultures. Conversely, the cells from the IL-3 induced blast cell colonies of the transgenic mice proliferated in response to either IL-3 or IL-5. Thus, the development of the progenitors can be equally supported by either IL-5 or IL-3, suggesting that intracellular signals from the IL-3R can be replaced by those from IL-5. These results strongly suggest that the lineage specificity of IL-5 is mainly due to the restricted expression of IL-5R alpha. PMID- 7869050 TI - Mechanism of interleukin 12-mediated toxicities during experimental viral infections: role of tumor necrosis factor and glucocorticoids. AB - Interleukin 12 (IL-12) doses in excess of 100 ng/d have been shown to induce profound immunotoxicities in mice infected with lymphocytic choriomeningitis virus (LCMV). These immunotoxicities are characterized by almost complete inhibition of virus-induced CD8+ T cell expansion and CTL activation, and up to 2 log increases in viral replication. They are accompanied by induction of serum tumor necrosis factor (TNF). The studies presented here were undertaken to characterize mechanisms for the IL-12-induced toxicities and to examine expression and function of TNF in this context. Several physiological changes were induced in IL-12-treated uninfected and dramatically elevated in IL-12 treated virus-infected mice. IL-12 induced (a) decreases in body weights, > 10% in uninfected and > 20% in LCMV-infected mice; (b) elevation of circulating glucocorticoid levels to > 10 micrograms/dl in uninfected and > 20 micrograms/dl in infected mice; and (c) decreases in thymic mass, > 30% in uninfected and up to 95% in infected mice. These changes are known to be associated with circulating TNF. Northern blot and in situ hybridization analyses demonstrated that IL-12 induced TNF-alpha expression and that LCMV infection synergized with IL-12 for induction of this factor. Antibodies neutralizing TNF reversed all of the IL-12 induced toxicities in LCMV-infected mice including the immunotoxicities against CD8+ T cells and anti-viral defenses. The TNF-mediated immunotoxicities appeared to result from an induced cellular sensitivity to the factor, as splenic leukocytes and CD8+ T cell subsets isolated from LCMV-infected mice were more sensitive to TNF-mediated cytotoxicity in culture than were equivalent populations prepared from uninfected mice. Experiments with the glucocorticoid type II receptor antagonist, RU486, demonstrated that endogenous glucocorticoids were secondary intermediaries in IL-12-induced thymic atrophy. Studies in IL-2 deficient mice showed that the synergism was dependent upon endogenous IL-2. The results delineate a unique mechanism of TNF-mediated toxicity. In addition, they have significant implications concerning potential detrimental consequences of in vivo TNF induction and of IL-12 administration for protective anti-viral responses. PMID- 7869051 TI - Pocket 4 of the HLA-DR(alpha,beta 1*0401) molecule is a major determinant of T cells recognition of peptide. AB - To investigate the functional roles of individual HLA-DR residues in T cell recognition, transfectants expressing wild-type or mutant DR(alpha,beta 1*0401) molecules with single amino acid substitutions at 14 polymorphic positions of the DR beta 1*0401 chain or 19 positions of the DR alpha chain were used as antigen presenting cells for five T cell clones specific for the influenza hemagglutinin peptide, HA307-19. Of the six polymorphic positions in the DR beta floor that were examined, mutations at only two positions eliminated T cell recognition: positions 13 (four clones) and 28 (one clone). In contrast, individual mutations at DR beta positions 70, 71, 78, and 86 on the alpha helix eliminated recognition by each of the clones, and mutations at positions 74 and 67 eliminated recognition by four and two clones, respectively. Most of the DR alpha mutations had minimal or no effect on most of the clones, although one clone was very sensitive to changes in the DR alpha chain, with loss of recognition in response to 10 mutants. Mutants that abrogated recognition by all of the clones were assessed for peptide binding, and only the beta 86 mutation drastically decreased peptide binding. Single amino acid substitutions at polymorphic positions in the central part of the DR beta alpha helix disrupted T cell recognition much more frequently than substitutions in the floor, suggesting that DR beta residues on the alpha helix make relatively greater contributions than those in the floor to the ability of the DR(alpha,beta 1*0401) molecule to present HA307-19. The data indicate that DR beta residues 13, 70, 71, 74, and 78, which are located in pocket 4 of the peptide binding site in the crystal structure of the DR1 molecule, exert a major and disproportionate influence on the outcome of T cell recognition, compared with other polymorphic residues. PMID- 7869052 TI - Activation of T cells recognizing self 60-kD heat shock protein can protect against experimental arthritis. AB - Lewis rats are susceptible to several forms of experimental arthritis-induced using heat-killed Mycobacterium tuberculosis (adjuvant arthritis, or AA), streptococcal cell walls, collagen type II, and the lipoidal amine CP20961. Prior immunization with the mycobacterial 65-kD heat shock protein (hsp65) was reported to protect against AA, and other athritis models not using M. tuberculosis, via a T cell-mediated mechanism. Hsp65 shares 48% amino acid identity with mammalian hsp60, which is expressed at elevated levels in inflamed synovia. Several studies have reported cross-reactive T cell recognition of mycobacterial hsp65 and self hsp60 in arthritic and normal individuals. We previously described nine major histocompatibility complex class II-restricted epitopes in mycobacterial hsp65 recognized by Lewis rat T cells. Of these only one, covering the 256-270 sequence, primed for cross-reactive T cell responses to the corresponding region of rat hsp60. Here we have tested each hsp65 epitope for protective activity by immunizing rats with synthetic peptides. A peptide containing the 256-270 epitope, which induced cross-reactive T cells, was the only one able to confer protection against AA. Similarly, administration of a T cell line specific for this epitope protected against AA. Preimmunization with the 256-270 epitope induced T cells that responded to heat-shocked syngeneic antigen-presenting cells, and also protected against CP20961-induced arthritis, indicating that activation of T cells, recognizing an epitope in self hsp60 can protect against arthritis induced without mycobacteria. Therefore, in contrast to the accepted concept that cross-reactive T cell recognition of foreign and self antigens might induce aggressive autoimmune disease, we propose that cross-reactivity between bacterial and self hsp60 might also be used to maintain a protective self reactive T cell population. This discovery might have important implications for understanding T cell-mediated regulation of inflammation. PMID- 7869053 TI - Interferon beta, a cofactor in the interferon gamma production induced by gram negative bacteria in mice. AB - The interferon (IFN) gamma production of splenocytes from closely related C57BL/10ScSn (Sn) and C57BL/10ScCr (Cr) mice was compared. Concanavalin A and CD3 monoclonal antibodies induced high levels of IFN-gamma in both Sn and Cr splenocytes. By contrast, treatment with gram-negative bacteria induced IFN-gamma only in Sn splenocytes; in Cr splenocytes, the IFN-gamma response was heavily impaired. The IFN-gamma induction by bacteria requires the cooperation of IFN gamma-producing cells with macrophages. Depletion of macrophages from Sn splenocytes resulted in the loss of ability to produce IFN-gamma after bacterial stimulation. Reconstitution with new Sn macrophages restored the IFN-gamma responsiveness, whereas reconstitution with Cr macrophages failed to do so. Normal function of IFN-gamma-producing cells and a defective function of macrophages of Cr mice was demonstrated by evidence showing that whole or macrophage-depleted Cr splenocytes, when supplemented with Sn macrophages, acquire the ability to produce IFN-gamma in response to bacteria. A similar effect was achieved by supplementing Cr splenocytes with supernatants of bacteria stimulated Sn macrophages or with recombinant murine IFN-beta or IFN-alpha. Preincubation of active macrophage supernatants with antibodies to IFN-beta suppressed the helper activity for Cr splenocytes. Moreover, the bacteria-induced production of IFN-gamma by Sn splenocytes could be inhibited by antibodies to murine IFN-beta. The results provide evidence that IFN-beta is an important cofactor of IFN-gamma induction, which is not induced in Cr mice by gram-negative bacteria. PMID- 7869054 TI - Mice from a genetically resistant background lacking the interferon gamma receptor are susceptible to infection with Leishmania major but mount a polarized T helper cell 1-type CD4+ T cell response. AB - Mice with homologous disruption of the gene coding for the ligand-binding chain of the interferon (IFN) gamma receptor and derived from a strain genetically resistant to infection with Leishmania major have been used to study further the role of this cytokine in the differentiation of functional CD4+ T cell subsets in vivo and resistance to infection. Wild-type 129/Sv/Ev mice are resistant to infection with this parasite, developing only small lesions, which resolve spontaneously within 6 wk. In contrast, mice lacking the IFN-gamma receptor develop large, progressing lesions. After infection, lymph nodes (LN) and spleens from both wild-type and knockout mice showed an expansion of CD4+ cells producing IFN-gamma as revealed by measuring IFN-gamma in supernatants of specifically stimulated CD4+ T cells, by enumerating IFN-gamma-producing T cells, and by Northern blot analysis of IFN-gamma transcripts. No biologically active interleukin (IL) 4 was detected in supernatants of in vitro-stimulated LN or spleen cells from infected wild-type or deficient mice. Reverse transcription polymerase chain reaction analysis with primers specific for IL-4 showed similar IL-4 message levels in LN from both types of mice. The IL-4 message levels observed were comparable to those found in similarly infected C57BL/6 mice and significantly lower than the levels found in BALB/c mice. Anti-IFN-gamma treatment of both types of mice failed to alter the pattern of cytokines produced after infection. These data show that even in the absence of IFN-gamma receptors, T helper cell (Th) 1-type responses still develop in genetically resistant mice with no evidence for the expansion of Th2 cells. PMID- 7869055 TI - Characterization of the cassette containing genes for type 3 capsular polysaccharide biosynthesis in Streptococcus pneumoniae. AB - The capsular polysaccharide is the major virulence factor of Streptococcus pneumoniae. Previously, we identified and cloned a region from the S. pneumoniae chromosome specific for the production of type 3 capsular polysaccharide. Now, by sequencing the region and characterizing mutations genetically and in an in vitro capsule synthesis assay, we have assigned putative functions to the products of the type-specific genes. Using DNA from the right end of the region in mapping studies, we have obtained further evidence indicating that the capsule genes of each serotype are contained in a gene cassette located adjacent to this region. We have cloned the region flanking the left end of the cassette from the type 3 chromosome and have found that it is repeated in the S. pneumoniae chromosome. The DNA sequence and hybridization data suggest a model for recombination of the capsule gene cassettes that not only describes the replacement of capsule genes, but also suggests an explanation for binary capsule type formation, and the creation of novel capsule types. PMID- 7869057 TI - In vivo fluorescence detection of human bladder carcinoma without sensitizing agents. AB - The diagnosis of transitional cell bladder carcinoma and especially carcinoma in situ of the bladder in spinal cord disordered persons is often made difficult by catheters, infections or stone-induced chronic inflammation. Fluorescence tagging of tumors by sensitizing agents such as hematoporphyrin derivatives enhances visualization but presents a number of drawbacks for the patients, even at low doses. We have developed a cystoscopic fiber optic instrument, based on a mercury arc lamp, for in vivo detection of human bladder carcinoma without sensitizing agents. The tissue autofluorescence upon UV excitation (365 nm) is detected and a demarcation contrast ratio for carcinoma in situ and transitional cell carcinoma of 2.6 and 3.2 respectively is obtained. This demarcation ratio is 60 percent higher than the contrast ratio obtained after photosensitizer injection. The integration of a reliable diagnostic method with a known efficient therapeutic technique (Nd YAG laser irridiation) opens the way for cost-effective preventive care of high-risk patients. PMID- 7869056 TI - Anergy and exhaustion are independent mechanisms of peripheral T cell tolerance. AB - We studied the interactions of male-specific T cell receptor (TCR)-alpha/beta transgenic (TG) cells with different concentrations of male antigen in vivo. We constructed mouse chimeras expressing different amounts of male antigen by injecting thymectomized, lethally irradiated mice with various ratios of male (immunoglobulin [Ig] Ha) and female (IgHb) bone marrow. These chimeras were injected with male-specific TCR-alpha/beta-trangenic cells. These experiments allowed us to monitor antigen persistence and characterize antigen-specific T cells in terms of their frequency, reactivity, and effector functions (as tested by elimination of male B cells in vivo). In the absence of antigen, virgin TG cells persisted but did not expand. Transient exposure to antigen resulted in cell expansion, followed by the persistence of increased numbers of antigen reactive T cells. In contrast, antigen persistence was followed by two independent mechanisms of tolerance induction: anergy (at high antigen concentrations), where T cells did not differentiate into effector functions but persisted in vivo as unresponsive T cells, and exhaustion (at lower antigen concentrations), where differentiation into effector functions (B cell elimination) occurred but was followed by the disappearance of antigen-specific T cells. PMID- 7869058 TI - DDAVP in the urological management of the difficult neurogenic bladder in spinal cord injury: preliminary report. AB - The purpose of this study is to determine the efficacy of desmopressin (DDAVP), a synthetic analogue of antidiuretic hormone, as an alternative therapy in the management of spinal cord injured (SCI) patients with neurogenic bladder dysfunction unresponsive to conventional therapy. Seven SCI patients (three men and four women) were treated with DDAVP after urodynamic evaluation. Despite treatment with anticholinergic agents, urodynamic evaluation demonstrated uninhibited detrusor contractions exceeding 30 cm H2O pressure at less than 300 ml cystometric capacity in all seven patients. Three patients had been managed with intermittent self-catheterization, but had socially unacceptable short intervals between catheterizations. Two women with incomplete injury were afflicted with significant nocturia (> 3 episodes/night). The remaining two patients managed with intermittent self-catheterization were troubled with nocturnal enuresis. The patients received 10 micrograms intranasal DDAVP once every 24 hours. Prior to DDAVP administration, the four patients who used DDAVP nightly experienced a median of four episodes of nocturia. After one month of DDAVP treatment, two patients had only one episode of nocturia per night and in the other two patients, nocturnal enuresis was completely eliminated. Three patients used daytime DDAVP administration at work to avoid frequent catheterization. The median period between bladder catheterizations increased from 2.5 hours before DDAVP to 6 hours while using DDAVP. Symptomatic improvement persisted during the follow-up period of 6-20 months (mean = 12). Side effects were infrequent; only one patient complained of transient headaches. Neither hyponatremia nor serum electrolyte abnormalities occurred. Our preliminary results suggest that DDAVP is safe and effective in the symptomatic management of complicated neurogenic bladder dysfunction in selected SCI patients. PMID- 7869059 TI - Hydronephrosis due to improper condom catheter use. AB - This report concerns a patient with bilateral hydronephrosis due to a tight external condom catheter retention strap. Urodynamics with fluoroscopy and cystoscopy failed to demonstrate bladder outlet obstruction, urethral stricture, uretero-vesicle junction abnormality, or other explanations for the bilateral hydronephrosis. The hydronephrosis resolved when the external condom catheter retention strap was eliminated. The authors emphasize the importance of patient education to prevent this problem and encourage alertness by clinicians to assess appropriateness of external condom catheter use. PMID- 7869060 TI - Axillofemoral bypass graft in a spinal cord injured patient with impending gangrene. AB - The axillofemoral bypass graft, an extra-anatomic graft, connects the axillary artery to the femoral artery and is used in the treatment of significant aortoiliac occlusive disease in poor-risk patients. A common indication for axillofemoral bypass is a "hostile abdomen" (postoperative adhesions, neoplasms or radiation). Less frequent indications are aortic mycotic aneurysm, infected aortobifemoral bypass graft, aortoduodenal fistula, inflammatory aneurysm and extensive retroperitoneal fibrosis. Spinal cord injured patients with peripheral arterial disease have two problems: 1) lack of premonitory symptoms (absence of claudication, paresthesias or rest pain) and 2) difficulty preventing pressure sores in the already poorly perfused limb. Indications for arterial reconstructive surgery are more drastic in this set of patients (impending gangrene and/or ischemic ulcers). Many spinal cord injured patients have sources of possible contamination (cystostomy and/or colostomy) which make intra abdominal clean surgery impossible. We present a spinal cord injured patient with a permanent cystostomy and impending gangrene of the left foot. He underwent a left axillofemoral bypass graft and had a good postoperative course. We conclude that axillofemoral bypass graft is a good alternative for limb salvage in the spinal cord injured patient, especially when there is a source of possible contamination (colostomy and/or cystostomy) that would interfere with more common bypass grafting. The role of the noninvasive vascular laboratory for early detection of vascular disease is emphasized. PMID- 7869061 TI - Waist and neck enlargement after quadriplegia. AB - Changes in waist and neck size in quadriplegic patients after paralysis, noted clinically, were assessed systematically. Twenty quadriplegic men, aged 60 +/- 13 years (mean +/- 1 SD) and 20 neurologically intact men, aged 63 +/- 17 years, selected by absence of weight gain, were questioned about changes in their waist and shirt collar sizes since the onset of paralysis (20 +/- 13 years) or during the previous 20 years for control subjects. Waist size expanded 7.0 +/- 0.3 inches for quadriplegic and 1.7 +/- 1.7 inches for control subjects (p < 0.001). Changes in neck size of 0.7 +/- 1.1 inches for quadriplegic and 0 +/- 0.7 inches for control subjects were found (p < 0.02). We conclude that quadriplegia is often followed by increased waist and neck size. These changes may relate to the impaired breathing mechanisms in quadriplegia. PMID- 7869062 TI - Falls on a neurorehabilitation unit: reassessment of a prevention program. AB - We conducted a retrospective case-control study of falls over a four year period on a 30 bed neurorehabilitation unit at the Burke Rehabilitation Hospital to characterize the nature of falls and identify factors associated with falling. The most common diagnoses treated on the unit were traumatic spinal cord injury, brain injury, and multiple sclerosis; stroke patients are treated on another service. Falls represented 72 percent of all incident reports made to the Nursing Office during the study period. One hundred seventeen (117) falls occurred in 82 patients during a time when the unit census was 28,622 patient days, yielding a rate of 1,439 falls per 1,000 patient years. One hundred fourteen (114) patients admitted with no history of falling during the same period were selected randomly for comparison. Most falls were associated with no injury (n = 96) or minor injury (n = 18). The most significant injuries occurred in three cases with lacerations requiring sutures. Falls occurred with greatest frequency during the first and fourth quartiles of the hospital stay, during the evening and while bed transfers were being performed. No association between falling and patient age, sex, diagnosis, number of medications, use of sedating medications, presence of motor, visual or cognitive impairment or orthostatic hypotension was evident. An increased risk of falling was associated with physician orders for Posey restraints. The implication of these findings for falls prevention programs is discussed. PMID- 7869063 TI - Exaggerated risks of chemicals. PMID- 7869064 TI - Predictive validity of the Nursing Severity Index in patients with musculoskeletal disease. Nurses of University Hospitals of Cleveland. AB - Prior studies have not examined the validity of severity of illness instruments in patients at low risk for mortality. We, therefore, examined the predictive validity of a newly developed instrument, the Nursing Severity Index in 5347 adult medical and surgical patients with musculoskeletal diagnoses admitted to an academic medical center in 1985-88. The Index is based on aggregating 34 clinical observations which were recorded by primary nurses during patient care; observations reflect biologic, functional, cognitive and psychosocial abnormalities. Other data, including patient demographic data and outcomes were obtained from hospital data bases. We found that, among all study patients, admission Nursing Severity Index scores were highly related (p < 0.001) to in hospital death rates-which were 0, 0.4, 0.8, 2.6, 6.7 and 23.5% in six hierarchical strata defined by the Index-and to nursing home discharge rates. In multivariate analyses, adjusting for diagnosis and other important covariates, each strata was associated with a 2.5-fold increased risk of mortality and a 1.6 fold increased risk of nursing home discharge. In addition, the Nursing Severity Index was an independent predictor (p < 0.001) of hospital charges and length of stay. We conclude that the Nursing Severity Index assesses multiple dimensions of illness, can be easily recorded during routine patient care, and accurately predicts hospital outcomes in an important 'low risk' group of patients. The validity of the Nursing Severity Index in other clinical subgroups should be further studied. PMID- 7869065 TI - Scientific and ethical aspects of genetic screening of workers for cancer risk: the case of the N-acetyltransferase phenotype. AB - Our expanding capacity to detect human genetic susceptibility to various chronic diseases presents us with the opportunity to screen asymptomatic people for purposes of employment, insurance or credit. It also brings with it the responsibility of deciding the ethical and social value of such applications. This paper addresses scientific and ethical issues involved in the use of genetic screening techniques which intend to identify individuals that have more than average susceptibility to develop cancer from workplace chemical exposures. The case in point is the genetic polymorphism for N-acetyltransferase activity and the risk of bladder cancer in workers exposed to carcinogenic arylamines. The acetyltransferase polymorphism is related to the metabolic activation and deactivation of carcinogenic arylamines. Any genetic screening test for cancer susceptibility must be based upon sound science. For example, it must be demonstrated that a specific metabolic phenotype is a risk factor for cancer and, further, that the available tests accurately classify the subjects as to the phenotype. If there is a poor correspondence between phenotype and genotype, or a large intra-individual variability in phenotype, misclassification may result. Also, bias, arising as a consequence of enzyme induction by specific substrates, must be ruled out. Genetic screening of workers for susceptibility to cancer seems to us an ethically unacceptable and premature, application of the science.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869066 TI - Maternal build and pregnancy outcome. AB - The effect of maternal build on the outcome of pregnancy was studied in two birth cohorts in Northern Finland, for 1966 and 1985-86. Prospectively collected data were available for 10,969 women in the earlier cohort and 9128 in the later one. The women in the earlier cohort were on average 2.9 cm shorter but 0.2 kg thinner and had 0.7 kg/m2 greater BMI. 13% of the women in the earlier cohort had a BMI below 20, but 24% in the later one, while 96% in both cohorts had BMI below 30. The women with low BMI were on average taller than the others, and at all BMI levels the women of the earlier cohort were shorter and lighter than those of the later one. The outcome of pregnancy was measured by the incidence of pre-term births and perinatal plus childhood deaths up to the age of 4 years, and the association of maternal body measurements with low birth weight (< 2500 g) and small for gestational age (SGA) infants was also studied. An additive logistic regression model was fitted in each analysis, to determine the probability of the outcome separately in terms of BMI, weight and height, adjusting for maternal age, parity, smoking, marital status, father's social class and place of residence. No evidence was found that BMI values 20-25, commonly judged as optimum for the mother's own longevity, predicted a better prognosis for the child than values below 20.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869067 TI - A comparison of anlaytic methods for non-random missingness of outcome data. AB - Missing outcome values occur frequently in survey data and are rarely missing randomly. Depending on the pattern of missingness, the choice of analytic method has implications for accuracy of the estimated outcome distribution as well as multivariate models. Data from a study of patterns of care in disabled elders were used to evaluate several common methods when missingness of the outcome was nonrandom. Results from single and multiple model-based imputation were compared with results from complete-case analysis and mean imputation. By ignoring nonrespondents' covariate information, the latter two methods yielded biased estimates of population means. Mean imputation and single model-based imputation underestimated standard errors by treating imputed values as if they were observed. Mean imputation also distorted the relationship between the outcome and predictors. Multiple model-based imputation provided an easily implemented method of adjustment for non-random non-response in both univariate and multivariate analyses. PMID- 7869068 TI - Tracking of serum lipids in children; association with the absolute lipid level- the cardiovascular risk in young Finns study. AB - We studied tracking of serum lipids in children and young adults (n = 248) during a 12-year follow-up. A novel method was developed for assessing tracking. It was based on the calculation of the absolute width of the individual track consisting of 5 serum lipid determinations. The total cholesterol (TC) track width tended to be broader in females compared to males (1.33 versus 1.24 standard deviation (SD) units). Approximately 35, 39, 24 and 13% of subjects had all 5 measurements within 1 SD (of the cohort mean) from serum TC, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides, respectively. However, variations in excess of 2.5 SDs were not rare. We also assessed the dependence of tracking on the absolute lipid level by calculating the SD of the standardized 6-year change in a cohort of 2236 children. In each serum lipid variable studied, lowest degree of tracking was found in highest lipid values. The mean changes were also largest in extreme values due to regression toward mean phenomenon. Our findings indicate that the width of longitudinal track of serum lipids may be two wide to reliably detect high risk children. Further, the track width was even broader in subjects with extreme serum lipid values. PMID- 7869069 TI - Development and validation of a claims based index for adjusting for risk of mortality: the case of acute myocardial infarction. AB - We developed a comorbidity index on a cohort of 162,699 Medicare beneficiaries who had an acute myocardial infarction (AMI) in 1987 and validate it on two national cohorts: (1) a cohort of 164,427 Medicare beneficiaries who had an AMI in 1988 and (2) a cohort of 10,466 patients admitted to Veterans Administration Hospitals (VAH) for AMI in 1988-1991. The impact of each sensitivity was expressed as; (1) the risk of mortality for those with the comorbidity, (2) the adjustment to the log odds for 2 year mortality and (3) the age-based likelihood of 2 year mortality. Models were validated by calculated the area under an ROC curve obtained by fitting a logistic regression model to each validation population. The two year mortality rate for 30-day survivors was approximately 30% in each of the 3 cohorts. The 5 most prevlent comorbidities coded in the developmental cohort were heart failure (34%), chronic angina (27%), minor arrythmias (25%) and uncomplicated hypertension (18%). Cancer was the most powerful predictor of 2 year mortality, impacting mortality the same as a 18.3 year age increase. Saturation (having all secondary diagnoses in the discharge summary filled) resulted in a 9.2 year age increase. Validation in the 1988 Medicare and in the Veterans Administration Hospitals cohorts resulted in areas of 73% and 72% under the respective ROC curves. Our methods can serve as a prototype for others wishing to assess comorbidity in other targeted subgroups. PMID- 7869070 TI - Recall bias in case-control studies: an empirical analysis and theoretical framework. AB - Previous work has suggested that recall bias in case-control studies may be more serious when the overall study quality is lower. This paper summarizes a systematic literature search to examine the question. All relevant studies published between 1966 and 1990 were included if they met the following criteria: (1) they represented original work, (2) they used a human population, (3) they used a case-control design, (4) they had a "validated" gold standard applied equally to cases and controls and (5) they reported at least one of crude agreement rates, chance-corrected agreement rates (kappa), sensitivity or specificity. Sixteen such studies were identified. No relationship was found between the absolute differences in agreement between cases and controls and the overall level of agreement, in contradiction to suggestions in previous literature. Comparisons of the data quality for cases and controls using either the crude agreement level, kappa, sensitivity, or specificity gave linear relationships with correlations of 0.81, 0.78, 0.58 and 0.62 respectively. Kappas were generally lower than the corresponding crude agreement levels and specificities were higher than sensitivities. When used together, these types of comparisons can give valuable information regarding (1) the possible existence of differential recall in a particular study and (2) the quality of that study, A theoretical framework is proposed for use in these areas. PMID- 7869071 TI - Reliability and validity of measures used to elicit health expectations, values, tradeoffs and intentions to be immunized for hepatitis B. AB - We evaluated measures eliciting health expectations, health values, health tradeoffs and intentions to take hepatitis B (HepB) vaccine among health science and technology students. We tested 23 students two weeks apart and then surveyed a cross-section of 373 students in 6 health disciplines. In a subsequent prospective study, 863 students were tested, invited to be immunized, and followed to observe who presented for immunization. The test-retest reliability coefficients exceeded 0.80 for all but the health value measures. All but the health values measures discriminated between those with strong and weak intentions to be immunized. Expectation measures discriminated among disciplines with different risks of exposure to blood and body fluids. The intention, health tradeoff and expectation measures discriminated between those who did and did not present themselves for immunization. We conclude that all but the health values measures met acceptable standards of reliability and validity. Health value tradeoff measures are more discriminating than health value measures. PMID- 7869072 TI - A comparison of overnight and 24 hour collection to measure urinary catecholamines. AB - The period of urine collection used to measure excretion of catecholamines varies in epidemiological practice. We set out to compare overnight with 24 hour collection. Twenty-four subjects each collected urine for 24 hours, with the overnight urine being separately collected. The correlation of overnight and 24 hour catecholamines was highest when both measures were standardised for creatinine excretion and when creatinine excretion was adjusted for urine flow rate. The observed correlations were 0.74 for dopamine, 0.81 for noradrenaline and 0.54 for adrenaline. The use of overnight collections may therefore require a sample size up to 1.5 times as large (for noradrenaline) or 3.4 times as large (for adrenaline) to achieve the same power as with 24 hour collections. However, the figures given exaggerate the advantage of 24 hour collections if these incorporate measurement errors that are not present in overnight collections. PMID- 7869073 TI - Population variation in migraine prevalence: a meta-analysis. AB - A meta-analysis of published studies was conducted to identify factors which explained variation in estimates of migraine prevalence. Twenty-four population based studies contributed a total of 168 gender and age specific estimates of migraine prevalence. In linear regression analysis, 70.6% of the variation in these prevalence estimates was explained by gender, age (AGE+AGE2), a binary variable for case definition, and an interaction term between age and the case definition. Initially, we identified five groups of case definitions among the 24 studies. Only the definition of Waters (any 2 of warning, nausea, or unilateral pain) was associated with statistically significant differences in prevalence estimates among studies; accordingly the other 4 groups were combined. Several other factors were examined as predictors of migraine prevalence including the method of selecting the study population, the source of the population, the response rate and whether diagnoses were confirmed by a clinical assessment. None of these factors substantially increased explained variance. We conclude that after taking sociodemographic factors and case definition into account, estimates of migraine prevalence are remarkably stable among studies. PMID- 7869074 TI - Evaluating the efficacy of cancer screening: clinical distinctions and case control studies. AB - To evaluate the efficacy of cancer screening, investigators have turned increasingly to the case-control approach as an efficient alternative design to the randomized controlled trial. Overlooked in the design and implementation of screening case-control studies, however, have been important clinical distinctions that are crucial for decisions in patient management and health policy. These distinctions involve the classification of baseline risk factors and prognostic co-morbidity, the enumeration and definition of the intervention, and the choice and timing of the outcome. When investigators neglect the distinctive characteristics of patients and their diseases, screening case control studies may have reduced validity and impaired utility. To strengthen the validity of these studies, investigators can analyze co-morbidity suitably, report a "clinical" confidence interval as the estimate of screening efficacy, carefully evaluate the attribution of death, and allow sufficient follow-up time for the death of patients diagnosed with cancer. Moreover, to strengthen the generalizability of screening case-control studies, investigators can stratify their findings for pertinent baseline risk factors and can expand the screening definition. If implemented, these guidelines may enhance the capacity of case control studies to provide clinicians and policy-makers with critically needed information on the efficacy of cancer screening. PMID- 7869075 TI - The quality of epidemiological data on coronary heart disease. PMID- 7869076 TI - An investigation of the relationship between antioxidant vitamin intake and coronary heart disease in men and women using discriminant analysis. AB - Smoking, high blood pressure and elevated blood cholesterol are the well established 'classical' risk factors for coronary heart disease (CHD) in men and women. However, it is also well-known that there is a considerable degree of residual variation in CHD after these factors have been taken into account. Consideration of antioxidant vitamin status may help to reduce this unexplained variation. Here, discriminant analysis is applied to the baseline cross-sectional data from the Scottish Heart Health Study. The problem of possible behavioural changes after diagnosis for CHD is addressed by analysing diagnosed and undiagnosed CHD cases separately. Results show that the combined dietary intakes of the antioxidant vitamins C, E and carotene (assessed using a food frequency questionnaire) differentiate CHD prevalence as well as do the classical risk factors. For women, stepwise discriminant analysis shows that the effect of the antioxidant vitamins on CHD is removed by adjustment for the classical risk factors and age. For men, however, the antioxidant vitamins still contribute to the discriminant function. It is concluded that dietary antioxidant vitamins appear to have a significant effect on the prevalence of CHD, especially amongst men. The benefits and problems of using discriminant analysis in this practical context are discussed, including the assumptions that need to be tested. PMID- 7869077 TI - An investigation of the relationship between antioxidant vitamin intake and coronary heart disease in men and women using logistic regression analysis. AB - Antioxidant vitamin intake (C,E and carotene) is assessed from a food frequency questionnaire applied to 10,359 middle-aged men and women participating in the Scottish Heart Health Study. Logistic regression analysis is then used to quantify the relationship between antioxidant vitamin consumption and prevalent coronary heart disease (CHD), analysing diagnosed and undiagnosed cases separately. For men, there is a protective effect of all three antioxidants, before and after adjustment for a comprehensive set of confounding variables. For women the picture is less clear, only vitamin C is negatively associated with CHD, but the effect is removed by adjustment. The logistic regression model is also used to determine classification rules for deciding whether or not an individual has CHD. The classification error rates using the antioxidants are found to be very similar to those found using smoking, blood pressure and serum total cholesterol as classification variables. Significant interactions are found for the antioxidants with smoking, cholesterol and age. It is concluded that antioxidant vitamin intake protects against CHD for men. Logistic regression analysis is compared with discriminant analysis, and is found to have important advantages as an epidemiological tool. PMID- 7869078 TI - Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. AB - The CA1 pyramidal neurons in the hippocampus are selectively vulnerable to transient ischemic damage. In experimental animals, the CA1 pyramidal neurons undergo cell death several days after brief forebrain ischemia. It remains, however, unknown whether this delayed neuronal death is necrosis or apoptosis. To investigate the degenerating processes of the CA1 pyramidal neurons in gerbil hippocampus after brief ischemia, lysosomal and nuclear alterations in the cells were examined using immunocytochemistry, in situ nick-end labeling, and Southern blotting. By light and electron microscopy, immunoreactivity for cathepsins B, H, and L, representative lysosomal cysteine proteinases, increased in the CA1 pyramidal neurons 3 d after ischemic insult, which showed cell shrinkage. By morphometric analysis, the volume density of cathepsin B-positive lysosomes markedly increased 3 d after ischemic insult, while that of autophagic vacuole like structures also increased at this stage, suggesting that cathepsin B immunopositive lysosomes increasing in the neurons after ischemic insult are mostly autolysosomes. Nuclei of the CA1 neurons were nick-end labeled by biotinylated dUTP mediated by terminal deoxytransferase 3 and 4 d after ischemic insult, but not in the prior stages. Simultaneously, dense chromatin masses appeared in nuclei of the neurons. By Southern blotting, laddering of DNA occurred only in CA1 hippocampal tissues obtained 4 d after ischemic insult. Confocal laser scanning microscopy demonstrated that the fragmented DNA in the CA1 pyramidal layer was phagocytosed by microglial cells. The results suggest that delayed death of the CA1 pyramidal neurons after brief ischemia is not necrotic but apoptotic. PMID- 7869079 TI - Oligodendrocytes originate in a restricted zone of the embryonic ventral neural tube defined by DM-20 mRNA expression. AB - Products of the PLP gene, proteolipid protein and its isoform DM-20, are the most abundant proteins in CNS myelin, and are markers of the oligodendrocyte, the myelin-forming cell in the CNS. The DM-20 transcript has previously been reported to be expressed in newborn oligodendrocyte progenitor cells and during embryonic development. We have therefore used a DM-20 cRNA probe to follow, by in situ hybridization, the oligodendrocyte lineage during embryonic development. DM-20 expressing cells were first detected at E9.5 in the ventricular germinal layer of the laterobasal plate of the diencephalon. At E14.5, DM-20+ cells had largely disappeared from the diencephalic ventricular germinal layer and had colonized the ventral mantle layer at the posterior part of the basal diencephalon. Between E17.5 and P1, the number of DM-20+ cells increased and progressively invaded the major white matter tracts. In the hindbrain, DM-20+ cells appeared at E12.5 in the caudal part of the rhombencephalon, and at E14.5 all along the ventral spinal cord. Between E14.5 and P1, DM-20+ cells progressively colonized, first ventrally then dorsally, all the spinal cord and more extensively the white matter tracts. At E14.5, a large gap separated, rostrally, the medullary columns from the mantle layer cells in the prosencephalon, suggesting that oligodendrocytes in the mid- and forebrain originate from a different pool of precursors than in the rhombencephalon and the spinal cord. Together, these observations suggest that expression of the DM-20 transcript is an early marker of commitment to the oligodendrocyte lineage, and that oligodendrocyte precursors originate in a ventrally restricted region. PMID- 7869080 TI - Characterization of K+ currents and the cAMP-dependent modulation in cultured Drosophila mushroom body neurons identified by lacZ expression. AB - Electrophysiological analysis of cultured neurons provides a potential approach toward understanding the physiological defects that may contribute to abnormal behavior exhibited by mutants of the fruit fly Drosophila. However, its application has been restricted by an inability to identify a particular functional or anatomical subpopulation of neurons from the CNS. To study neurons composing the CNS mushroom body proposed as a center for insect olfactory learning, we utilized a Drosophila enhancer detector line that expresses a lacZ reporter gene in these neurons and identified them in acutely dissociated larval CNS cultures by vital fluorescent staining. The patch-clamp analysis suggests that whole-cell voltage-activated K+ currents can be classified into two types in identified mushroom body neurons. Type 1 current comprises a TEA-sensitive slowly inactivating current and noninactivating component while type 2 current contains a 4-AP-sensitive transient A-current and a noninactivating component. Application of cAMP analogs induced distinct modulation of type 1 and type 2 currents. Our results demonstrate that the expression of the lacZ gene and the subsequent staining do not significantly alter the different types of K+ currents. This initial characterization provides a basis for further analysis of mutations that impair learning and memory resulting from an abnormal cAMP cascade preferentially expressed in the mushroom body. PMID- 7869081 TI - Genetic transformation of the synaptic pattern of a motoneuron class in Caenorhabditis elegans. AB - Caenorhabditis elegans possesses two classes of inhibitory locomotory neurons, the DD and VD motoneurons (mns), and they form complementary components of a cross-inhibitory neuronal network innervating dorsal and ventral body muscles. The DD and VD mns (collectively called the D mns) share a number of morphological and neurochemical features, and mutations in a number of different genes disrupt both cell types in identical ways; however, the DD and VD mns have different lineal origins and different synaptic patterns. Given the number of phenotypic features shared by the D mns, it was of interest to determine what is responsible for the synaptic patterns that distinguish them. An analysis of the locomotory defect along with a genetic epistasis test suggested that unc-55 mutations alter the function of the VD but not the DD mns. Correlated with the defective locomotory behavior of unc-55 mutants was an alteration in the distribution of varicosities, structures associated with presynaptic elements, on the VD mns. The pattern of varicosities of the unc-55 VD mns resembled that of the wild-type DD mns. Moreover, the selective removal of the DD mns revealed that unc-55 VD mns had adopted a functional role appropriate for the DD mns. Thus, unc-55 appears to be involved in producing the synaptic patterns that distinguish the two D mn classes from one another; when the gene is mutated the VD and DD mns become structurally similar and functionally equivalent. PMID- 7869082 TI - BDNF and NT-4/5 exert neurotrophic influences on injured adult spinal motor neurons. AB - Adult motor neurons, like their immature antecedents, express the mRNA for the signaling receptor for brain-derived neurotrophic factor (BDNF) and for neurotrophin-4/5 (NT-4/5). However, while both BDNF and NT-4/5 support the survival of axotomized developing spinal motor neurons in vitro or in vivo, it is not known whether these factors continue to influence spinal motor neurons in adulthood. The present study tests if BDNF or NT-4/5 modulate the reactive responses of adult spinal motor neurons to nerve injury. We utilize sciatic nerve transection to axotomize the spinal motor neurons that form the retrodorsal lateral nucleus (RDLN) and show that, after axotomy, RDLN motor neurons lose ChAT immunoreactivity and also reexpress p75Ingfr, the low affinity receptor for all neurotrophin family members. Treatment with BDNF or NT-4/5 alters these effects of sciatic nerve transection. Both BDNF and NT-4/5 attenuate the loss of ChAT expression in axotomized RDLN motor neurons; thus, as compared to vehicle treatments, BDNF and NT-4/5 produce statistically significant increases in the optical density of ChAT immunostaining. Furthermore, BDNF and NT-4/5 also significantly increase the RDLN reexpression of p75Ingfr after sciatic nerve transection. Interestingly, essentially identical increases in RDLN ChAT and p75Ingfr immunostaining are produced by sciatic nerve crush injuries in the absence of exogenous neurotrophin treatment. These data show that treatment with exogenous BDNF and NT-4/5 changes the response of adult spinal motor neurons to sciatic nerve transection. Furthermore, these neurotrophins elicit reactive responses in axotomized motor neurons that mimic those produced by endogenous agents in regenerating crushed peripheral nerve. PMID- 7869083 TI - Type-specific stabilization and target-dependent survival of regenerating ganglion cells in the retina of adult rats. AB - Axotomy-induced degradation of retinal ganglion cells (RGC) can be delayed if the destructive features of activated microglial cells are pharmacologically neutralized, and prevented if the axons are permitted to regrow into transplanted autologous peripheral nerve (PN) pieces. This study was undertaken to classify the regenerating rat RGC and to examine target-dependent effects on survival of subsets of neurons. In analogy to the normal rat retina, we have categorized the retrogradely labeled, regenerating RGC into five classes which are morphologically distinct and reminiscent of normal RGC correlates (types I, II, III, delta-cells, and displaced RGC). Six weeks after transplantation of peripheral nerve to the transected optic nerve, large, type I-like cells (RI) constituted 5.7 +/- 2.0% of the total population. Smaller, round to oval cells of type RII represented the majority of labeled neurons (64.5 +/- 6.1%). Cells of type RIII constituted 4.6 +/- 1.7% of the total population and had very typical, middlesized, polarized perikarya and large dendrites. Less frequent (< 1%) were R delta and displaced RGC. Transplantation of a PN graft which was not reconnected with a central target (blind-ending group) and monitoring of the extant neurons showed a progressive disappearance of the regenerating RGC, such that 6 months after surgery predominantly few large cells survived. When the retinas were treated with macrophage/microglia-inhibiting factor (MIF), and the regenerating axons were guided into the pretectum, predominantly large RGC of type RI survived. Guidance of the axons into their major natural target, the superior colliculus (SC), resulted in selective survival of many small, RII-like RGC. Calculation of the dendritic coverage factors for the major types of RGC revealed that dendrites of the most abundant small cells of type RII overlapped uniformly and covered the retinal surface completely, whereas cells of types RI and RIII did not suffice for surface coverage. The results suggest that combined suppression of axotomy-induced microglial activation and guidance of regenerating axons with a PN graft into central targets is a suitable technique to produce sufficient numbers of regenerating axons which may retrieve some functional properties. Target-specific neuronal contacts are likely involved in morphological stabilization and better survival of regenerating neurons. PMID- 7869084 TI - Language-related field potentials in the anterior-medial temporal lobe: I. Intracranial distribution and neural generators. AB - Field potentials were recorded from intracranial electrodes in humans to study language-related processing. Subjects viewed sentences in which each word was presented successively in the center of a video monitor. Half of the sentences ended normally, while the other half ended with a semantically anomalous word. The anomalous sentence-ending words elicited a large negative field potential with a peak latency near 400 msec, which was focally distributed bilaterally in the anterior medial temporal lobe (AMTL), anterior to the hippocampus and near the amygdala. Subdural electrodes positioned near the collateral sulcus just inferior and lateral to the amygdala recorded a positive field potential at the same latency. This spatial distribution of voltage suggested that this language sensitive field potential was generated in the neocortex near the collateral sulcus and anterior fusiform gyrus. Additional task-related field potentials were recorded in the hippocampus. The AMTL field potential at 400 msec shares characteristics with the N400 potential recorded from scalp electrodes that has been associated with semantic processing. PMID- 7869085 TI - Language-related field potentials in the anterior-medial temporal lobe: II. Effects of word type and semantic priming. AB - Field potentials were recorded from intracranial electrodes in humans to study the role of the anterior medial temporal lobe (AMTL) in language-related processing. Subjects viewed lists of words in which orthography and word type varied, or in which words were primed by semantic associates. Large negative field potentials were elicited within the AMTL by isolated words. The amplitude and intracranial distribution of these AMTL field potentials were consistent with those in our previous study in which anomalous sentence-ending words were used as stimuli (McCarthy et al., in press). The neocortex, in the region of the collateral sulcus and anterior fusiform gyrus, was identified as the likely neural generator of this field potential. The AMTL field potential was diminished by semantic priming, and was larger for words with semantic content than for words serving grammatical function. Orthographically illegal nonwords did not elicit this field potential. The N400 scalp event-related potential (ERP) has been shown to respond in the same manner to these task manipulations (Nobre and McCarthy, 1994), and, thus, the AMTL field potential was proposed to contribute to the generation of N400. The possible roles in language processing reflected by the AMTL field potential were considered. PMID- 7869086 TI - The impact of basal forebrain lesions on the ability of rats to perform a sensory discrimination task involving barrel cortex. AB - Depletion of cortical acetylcholine (ACh) correlates with reduced stimulus-evoked 2-deoxyglucose (2-DG) uptake in rodent somatosensory cortex. We examined the effect of unilateral basal forebrain lesions and subsequent cortical ACh depletion on (1) the ability of rats to detect a passively applied deflection of the whiskers, and (2) whisker-evoked 2-DG uptake. Normal adult rats were trained on a T-maze to respond by turning in one direction if the whiskers were displaced and in the opposite direction on presentation of a sham stimulus; only the left set of whiskers was stimulated. When the animal performed at the 80% correct level for three consecutive sessions (criterion), it was randomly assigned to a group receiving either a saline injection (sham lesion) or an ibotenic acid injection (excitotoxic lesion) into the right basal forebrain. Behavioral testing continued until the animal returned to the prelesion criterion, at which time a terminal 2-DG experiment was conducted. None of the sham-lesioned rats experienced disruption of their ability to perform the task. All excitotoxic basal forebrain-lesioned rats were impaired in task performance, but eventually returned to prelesion performance levels. The length of time required to return to criterion was positively correlated with the amount of cortical ACh depletion. Despite the behavioral recovery of the ACh-depleted rats, 2-DG uptake in response to whisker stimulation continued to be reduced in the somatosensory cortex ipsilateral to the basal forebrain lesion. These findings suggest that ACh depletion, which results in a long-lasting decrease in neuronal responses to evoked stimuli, transiently impairs an animal's ability to perceive and appropriately respond to sensory information; the duration of impairment is related to the degree of depletion. PMID- 7869087 TI - Dynamics of granule cell migration: a confocal microscopic study in acute cerebellar slice preparations. AB - Real-time examination of Dil-labeled, immature granule cells in cerebellar slice preparations reveals several temporal and cytological aspects of neuronal migration that have not been observed in previous in vivo or in vitro systems. Using confocal microscopy we have obtained evidence that rates of cell movement depend critically on the age of the cerebellum. Although there were considerable variations in the speed of individual cells, the average rate of cell migration increased systematically from 9.6 +/- 3.0 microns/hr in cerebella from 7-d-old mice to 18.0 +/- 2.9 microns/hr in cerebella from 13-d-old mice. Consequently, granule cells traversed the developing molecular layer within a relatively constant time period despite the doubling in width of the molecular layer during the second week of postnatal life. Granule cell movement was characterized by alternations of short stationary phases with movement in a forward or backward direction. The net displacement of a cell depended on the duration and frequency of these phases as well as on the speed of movement. Changes in the relative position of Dil crystals attached to the surface of granule cells suggested the existence of a complex topographical flow of plasma membrane during migration. Although a large portion of the plasma membrane seemed to move in register with the nucleus and surrounding cytoplasm, new membrane appeared to be incorporated primarily at the leading process. However, the pattern of membrane flow at the interface between migrating neurons and Bergmann glial fibers could not be determined, since these sites could not be labeled by Dil crystals. The present results are in harmony with the concept that multiple cellular/molecular mechanisms may be engaged in granule cell migration. PMID- 7869088 TI - Determinants of postural orientation in quadrupedal stance. AB - The purpose of this study was to investigate the determinants of postural orientation by examining stance kinematics and kinetics at various interpaw distances. Four adult cats were trained to stand, unrestrained, on a force platform. Three-dimensional ground reaction forces and kinematics, as well as EMG activities, were recorded during stance at five different anteroposterior (AP) distances and two widths. Stance distance was varied by changing the distance between the four force plates mounted on the platform. All cats used a strategy of maintaining a constant horizontal orientation of the trunk and levering the limbs at the girdles while maintaining constant intralimb geometry to accommodate the changes in stance distance. The direction of the ground reaction forces covaried with the limb axes. As a result, the joint torques were conserved in the forelimb, and varied within small ranges in the hind. Increased tonic activity in the extensors of the back, the hip, and the ankle was observed at shorter distances while increased knee extensor activity was observed at longer distances. A cost function, defined as the sum of squared 3-D joint torques, was minimal for the hindlimb at a stance distance which corresponded to the preferred distance naturally assumed by each cat on the floor. Thus, in the maintenance of stance posture, trunk orientation and intralimb geometry is constrained, the goal of which is to minimize muscular effort or energy expenditure. PMID- 7869090 TI - Depolarization inactivation of dopamine neurons: an artifact? AB - A widely accepted theory postulates that, in rats, chronic treatment with neuroleptics causes the depolarization inactivation of the majority of midbrain dopamine (DA) neurons. The present study was aimed to verify whether general anesthesia and/or other factors might contribute to the depolarization inactivation of A9 and A10 DA neurons. To investigate on the possible role played by DA receptor subtypes, three representatives DA antagonists were used: haloperidol (a mixed D1/D2), (-)-sulpiride (a selective D2) and SCH 23390 (a selective D1). In agreement with previous studies, where neuronal sampling was carried out in animals under chloral hydrate anesthesia, chronic treatment with haloperidol (0.5 mg/kg daily for 21-28 d) produced a profound reduction (about 80%) in the number of spontaneously active A9 DA neurons. However, when neuronal sampling was performed in unanesthetized rats, the single administration of haloperidol, (-)-sulpiride, or SCH 23390 (0.5, 25, and 0.3 mg/kg respectively 2-3 hr beforehand) increased the number of spontaneously active A9 and A10 DA neurons and their firing rate, whereas the chronic administration of these drugs (daily for 21-28 d) failed to reduce the number of spontaneously active A9 and A10 DA neurons. The inhibitory effect of apomorphine on the firing rate of A9 and A10 DA neurons was prevented 3-4 hr after the acute or last injection of chronic haloperidol or (-)-sulpiride. However, the inhibitory effect was potentiated 24 hr after the last administration of the chronic regimen with these neuroleptics, but it was not influenced by either acute or chronic treatment with SCH 23390.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869089 TI - Cloning and characterization of a calcium channel alpha 1 subunit from Drosophila melanogaster with similarity to the rat brain type D isoform. AB - We report the complete sequence of a calcium channel alpha 1 subunit cDNA cloned from a Drosophila head cDNA library. This cDNA encodes a deduced protein containing 2516 amino acids with a predicted molecular weight of 276,493. The deduced protein shares many features with vertebrate homologs, including four repeat structures, each containing six transmembrane domains, a conserved ion selectivity filter region between transmembrane domains 5 and 6, and an EF hand in the carboxy tail. The Drosophila subunit has unusually long initial amino and terminal carboxy tails. The region corresponding to the last transmembrane domain (IVS6) and the adjacent cytoplasmic domain has been postulated to form a phenylalkylamine-binding site in vertebrate calcium channels. This region is conserved in the Drosophila sequence, while domains thought to be involved in dihydropyridine binding show numerous changes. The Drosophila subunit exhibits 78.3% sequence similarity to the rat brain type D calcium channel alpha 1 subunit, and so has been designated as a Drosophila melanogaster calcium channel alpha 1 type D subunit (Dmca1D). In situ hybridization shows that Dmca1D is highly expressed in the embryonic nervous system. Northern analysis shows that Dmca1D cDNA hybridizes to three size classes of mRNA (9.5, 10.2, and 12.5 kb) in heads, but only two classes (9.5 and 12.5 kb) in bodies and legs. PCR analysis suggests that the Dmca1D message undergoes alternative splicing with more heterogeneity appearing in head and embryonic extracts than in bodies and legs. PMID- 7869091 TI - 3-Hydroxyanthranilic acid oxygenase-containing astrocytic processes surround glutamate-containing axon terminals in the rat striatum. AB - Glutamate, the major transmitter of the corticostriatal pathway, is present in abundance in the striatum. 3-Hydroxyanthranilic acid oxygenase (3HAO) is the biosynthetic enzyme for quinolinic acid, an endogenous agonist of the NMDA glutamate receptor subtype and a potent neurotoxin. In order to explore the anatomical basis of possible functional interactions between glutamate and quinolinic acid in the rat striatum, pre- and postembedding immunocytochemical methods were used to localize 3HAO immunoreactivity (-i) and glutamate-i at the electron microscopic level. In accordance with previous light microscopic and biochemical studies, 3HAO-i was detected exclusively in astrocytes throughout the striatum. Notably, 3HAO-i was present in fine-caliber glial processes that often surrounded or abutted synaptic profiles, both asymmetric and symmetric. Glutamate i was heavily deposited (3-13-fold higher gold particle density than tissue average) in axon terminals forming asymmetric synapses with spines and, occasionally, dendrites. In contrast, terminals forming symmetric synapses, dendrites, neuronal somata, and glial cells contained significantly less labeling than terminals forming asymmetric synapses. In double-labeled material, 3HAO-i was observed in glial processes that partially surrounded or were adjacent to glutamate-labeled terminals forming asymmetric synapses. 3HAO-labeled glial processes were also adjacent to unlabeled terminals forming symmetric synapses. Since quinolinic acid is known to enter the extracellular compartment readily, these results suggest that astrocytic quinolinic acid may participate in the regulation of glutamatergic neurotransmission in the rat striatum. PMID- 7869092 TI - Variants of olfactory memory and their dependencies on the hippocampal formation. AB - Olfactory memory in control rats and in animals with entorhinal cortex lesions was tested in four paradigms: (1) a known correct odor was present in a group of familiar but nonrewarded odors, (2) six known correct odors were simultaneously present in a maze, (3) correct responses required the learning of associations between odors and objects, and (4) six odors, each associated with a choice between two objects, were presented simultaneously. Control rats had no difficulty with the first problem and avoided repeating selections in the second; this latter behavior resembles that reported for spatial mazes but, in the present experiments, was not dependent upon memory for the configuration of pertinent cues. Control animals varied considerably in their acquisition of odor object associations with only a subgroup learning every set of pairings. These latter animals also performed well in the fourth task and, as indicated by post hoc analyses, developed complex strategies in dealing with the problem of serial odor-object pairs. Lesioned animals had no difficulty in selecting correct odors learned prior to surgery (problem one) but repeated their choices in problem two. This latter result suggests that hippocampus contributes to the transient memory of prior choices for odors as it does for prior choices in spatial mazes. Entorhinal rats were able to form odor-object associations (problem three), and a subgroup of the animals periodically succeeded in doing a long series of such choices (problem four), though with less frequency than controls. These results indicate that rats use both long-term memory and transient memory in dealing with olfactory problems and suggest that the second of these is dependent upon a hippocampal process that encodes a type of information other than the relationship between cues. PMID- 7869093 TI - Enhanced survival and neuronal differentiation of adrenal chromaffin cells cografted into the striatum with NGF-producing fibroblasts. AB - Although adrenal medullary chromaffin cells have been used extensively for intracerebral grafting, their survival has generally been poor. Improved survival of the implanted cells has been achieved by exposing the chromaffin cells to NGF in vivo. Culture studies have shown, however, that chromaffin cells are converted into sympathetic neurons when NGF is included in the medium. The degree to which such a transdifferentiation may occur in vivo has not been determined. We assessed the effects of cografting chromaffin cells with primary fibroblasts genetically engineered to express NGF. Chromaffin cells from 10 d old rats were implanted with NGF-producing or beta-galactosidase-producing primary fibroblasts (control fibroblasts) into the striatum of 6-hydroxydopamine treated adult rats of the same strain. Eight weeks postgrafting, chromaffin cells cografted with NGF producing fibroblasts displayed many of the features of mature sympathetic neurons such as large somata, long processes, transmitter vesicles similar to those found in neurons, and positive immunolabeling for the neuronal markers neurofilament, MAP2 and SCG10. Chromaffin-derived neuron number was also significantly enhanced in the presence of NGF-producing fibroblasts. While control fibroblasts were also found to increase chromaffin cell number above that of chromaffin cells grafted alone, the control fibroblasts did not induce neuronal transdifferentiation. These results demonstrate that chromaffin cells cografted with NGF-producing fibroblasts undergo transdifferentiation in vivo and express many characteristics of mature sympathetic neurons. The consequences of this transdifferentiation on the long term survival and function of the transplanted cells in vivo remain to be clarified. PMID- 7869094 TI - A selection model for motion processing in area MT of primates. AB - A computational model for motion processing in area MT is presented that is based on the observed response properties of cortical neurons and is consistent with the visual perception of partially occluded and transparent moving stimuli. In contrast to models of motion processing that assume spatial continuity and fail to compute the correct velocity for these visual stimuli, our model produces a distributed segmentation of the image into disjoint patches that represent distinct objects moving with common velocities. A key element in the model is the selection of regions of the visual field where the velocity estimates are most reliable. The processing units in the motion model that perform the selection have nonclassical receptive fields similar to those observed in area MT (Allman et al., 1985). The psychophysical responses of the model to coherently moving random dots and transparent plaid gratings are similar to those observed in primates. PMID- 7869095 TI - Migratory paths of neurons and glia in the embryonic chick spinal cord. AB - To study the migration of chick spinal cord neurons, we labeled individual cells in the ventricular zone with recombinant retroviruses, then identified their progeny histochemically. First, we analyzed cell mixing in the ventricular zone. Some clones labeled at early neural tube stages spread widely along both the dorsoventral and rostrocaudal axes. However, clones labeled later were confined to narrow domains along both axes. These results imply that displacement of cells within the ventricular zone becomes progressively restricted. Second, we studied the migration of cells out of the ventricular zone by infecting embryos at a fixed stage and varying the time of analysis. At first, most clones consisted of radial arrays of cells, suggesting that the initial migration is predominantly radial. In many clones, however, neurons turned orthogonally from parental radial arrays and migrated along the path of circumferentially oriented axons. By hatching, clonally related cells in the gray matter were usually distributed in narrow transverse slabs, but some white matter glial cells had migrated longitudinally for up to several segments. We conclude that the dispersal of clonally related cells results from (1) early mixing of progenitors within the neural tube; (2) radial stacking of progeny in the ventricular zone; (3) migration of progeny from the ventricular zone in spoke-like routes; (4) circumferential migration of some neurons along axons; (5) short-distance dispersal of differentiating neurons; and (6) a late, longitudinal migration of glia through white matter tracts. Finally, we show that floor plate cells differ from other spinal cord cells in both their lineage and migration patterns. PMID- 7869096 TI - Presynaptic enhancement of inhibitory synaptic transmission by protein kinases A and C in the rat hippocampus in vitro. AB - The protein kinase C activator phorbol 12,13-dibutyrate (0.5 microM, PDBu) and the protein kinase A activator forskolin (20 microM) each increased evoked monosynaptic inhibitory postsynaptic current (IPSC) amplitude, without affecting its reversal potential, and increased the frequency of miniature IPSCs (mIPSCs), without affecting their amplitude or kinetics, as assessed with whole-cell recording form CA3 pyramidal cells in hippocampal slice cultures. The effects of forskolin and PDBu on both evoked IPSC amplitude and mIPSC frequency were additive and were antagonized by inhibitors of protein kinases A and C, respectively. The kinase activator-induced increases in mIPSC frequency were quantitatively comparable to the increases in evoked IPSC amplitude. The increases in mIPSC frequency were not attenuated by the voltage-dependent calcium channel blocker Cd2+ (100 microM). We conclude that stimulation of protein kinases A and C potentiates hippocampal inhibitory synaptic transmission through independent presynaptic mechanisms of action. Kinase-induced potentiation of spontaneous release does not require modulation of axon terminal Ca2+ channels. This mechanism may also contribute substantially to the potentiation of evoked release. PMID- 7869097 TI - Identification and characterization of antidepressant-sensitive serotonin transporter proteins using site-specific antibodies. AB - Serotonin (5HT) transporters (SERTs) are responsible for clearance of synaptic and plasma 5HT and are molecular targets for multiple therapeutic and addictive compounds. Recently brain and peripheral SERT cDNAs have been cloned and characterized functionally in transfected cells. Antipeptide (S365) and anti fusion protein (CT-2) antibodies, directed at epitopes poorly conserved among other Na+/Cl- cotransporters, have been prepared to facilitate the identification and characterization of SERT proteins in native and transfected cells. Immunoprecipitations and immunoblots of rat/human SERT-transfected HeLa cells reveal specific SERT-immunoreactive glycoproteins absent from extracts of vector transfected cells and absent when incubations were conducted using peptide- or fusion protein-absorbed antibody. In SDS-PAGE of membranes prepared from rat midbrain and cortex, SERTs migrate as single 76 kDa polypeptides with a relative abundance consistent with the known distribution of 5HT neurons and axonal projections. SERT-immunoreactive proteins are also detectable in platelet and pulmonary membranes, sites of peripheral 5HT uptake, but not in liver. Our studies also indicate that brain and platelet SERTs are formed from identical polypeptides differing significantly in their extent of N-linked glycosylation. Immunocytochemistry performed on rat brain sections with CT-2 antibody revealed SERT expression associated with brainstem raphe nuclei in a pattern virtually identical to that obtained by labeling adjacent sections with 5HT antisera. SERT immunoreactive fibers were found to be widely distributed throughout the rodent brain, with highest density in forebrain regions known to receive a dense serotonergic innervation. In a similar manner, CT-2 antibody also detects endogenous expression of human SERT proteins, providing an opportunity for future studies on the modulation of transporter protein expression in neurologic and psychiatric disorders. PMID- 7869098 TI - Postsynaptic modifications in long-term facilitation in Aplysia: upregulation of excitatory amino acid receptors. AB - Long-term sensitization of the gill and siphon withdrawal in Aplysia is accompanied by facilitation of sensorimotor synaptic connections that depends on new protein synthesis. This phenomenon has been previously shown to involve presynaptic growth. At the postsynaptic level, a reorganization should occur to parallel the formation of new synaptic contacts. We show here that 24 hr following an application of 5-HT, which produces long-term synaptic facilitation (LTF), the response of the motoneuron to an excitatory amino acid agonist of the synaptic receptors is increased. General inhibition of protein synthesis with anisomycin blocks this enhancement. Inhibiton of protein synthesis limited to the postsynaptic neuron by intracellular injection of gelonin, a ribosome inactivating toxin, also blocks the increase in the response to the agonist but fails to block 24 hr LTF. These results are compatible with a model of LTF that involves coordinate pre- and postsynaptic changes. The latter may include an upregulation of functional postsynaptic receptors. These may not be initially required for LTF measured at a 24 hr time point, but could become necessary for later stages of LTF. An increase in the number of functional postsynaptic receptors in a reserve pool may also prime the postsynaptic neuron for subsequent learning-associated plasticity. PMID- 7869099 TI - Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine. AB - Microdialysis in behaving animals was used to concomitantly characterize the dopamine and 5-HT responses in the caudate and the norepinephrine response in the hippocampus to the D- and L-isomers of amphetamine and methamphetamine. Doses of all four drugs which promoted similar stereotypy responses produced a D amphetamine-like response profile of dopamine and dopamine metabolites, suggesting that all these drugs interact with dopamine systems to facilitate the release of transmitter. However, in contrast to the similar behavioral profiles, the magnitude of the dopamine responses diverged significantly. In addition, all four drugs increased extracellular norepinephrine and 5-HT, but the relative responses differed markedly from dopamine and from each other. The contrasting structure-activity relationships for these drugs likely reflect their differential potency at the various neuronal uptake transporters in promoting either transmitter release, and/or uptake blockade. In addition, the interaction of each drug at the vesicular transporters, as well as the availability of a cytoplasmic pool of transmitter likely also contribute to the neurotransmitter response. Because of the particularly divergent transmitter response profiles exhibited by L-methamphetamine, its behavioral and neurotransmitter effects were characterized over a more extended range of doses. Although the duration of the increase in extracellular dopamine was clearly proportional to dose, the dose dependent increases in the magnitude of the dopamine response did not parallel the behavioral profiles. The results of these studies indicate that, while the dopamine, norepinephrine and 5-HT responses to these drugs probably contribute to the expression of stimulant-induced behaviors, simple relationships between the neurotransmitter responses and the behavioral profiles were not evident. PMID- 7869100 TI - Mitochondria and Na+/Ca2+ exchange buffer glutamate-induced calcium loads in cultured cortical neurons. AB - Utilizing Indo-1 microfluorimetry, we have investigated the role of mitochondria and Na+/Ca2+ exchange in buffering calcium loads induced by glutamate stimulation or depolarization of cultured rat forebrain neurons. A 15 sec pulse of 3 microM glutamate or 50 mM potassium with veratridine was followed by a 2 min wash with a solution containing either Na(+)-free buffer or the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), or both. For glutamate induced Ca2+ loads, a Na(+)-free wash delayed recovery to baseline by twofold, mitochondrial uncoupling delayed recovery by greater than fourfold, and the combined treatment essentially prevented recovery of [Ca2+]i for the duration of the wash. Although the depolarization stimulus was able to elicit a larger peak [Ca2+]i, the neurons required significantly less time to recover from depolarization-induced Ca2+ loads after identical wash manipulations, indicating a fundamental difference between calcium loads induced by glutamate as opposed to those induced by depolarization. We show evidence that the delayed recovery is not primarily the result of perturbations in intracellular pH regulation and have also demonstrated that a substantial portion of the delayed recovery is independent of Ca2+ entry during the washout phase. We conclude that glutamate and depolarization both induce Ca2+ loads whose buffering is critically dependent on functional mitochondria and secondarily reliant on Na+/Ca2+ exchange. The two systems overlap and seem to be responsible for buffering most of the glutamate induced Ca2+ load, because manipulations that compromised both systems completely disabled the neurons' ability to recover [Ca2+]i to baseline. PMID- 7869101 TI - The influence of heregulins on human Schwann cell proliferation. AB - The use of Schwann cell (SC) autotransplantation to influence neural repair in humans is dependent upon identifying mitogens that will effectively expand human Schwann cells (SCs) in culture. The recent purification and molecular cloning of glial growth factor (GGF), a potent mitogen for rat Schwann cells, has led to the recognition that a family of proteins (GGF/HRG/NDF/ARIA) are alternatively spliced products of a single gene. The heregulins (HRGs) have been characterized with respect to their influence on human breast cancer cell lines; here we examined whether the HRGs have mitogenic activity for human SCs. Using DNA synthesis assays and serial passaging of cells in culture, we demonstrate that HRG is an effective mitogen for human SCs and that, in the presence of agents that elevate cAMP, it is possible to expand these cells over multiple passages without overwhelming fibroblast contamination. One putative target for this family of proteins is p185erbB2, and EGF-like receptor tyrosine kinase that is encoded by the erbB2 protooncogene. In this report we also demonstrate that the erbB2/3/4 messages as well as the erbB2/3 receptor proteins are present within cultured human SCs. The addition of HRG to human SCs results in tyrosine phosphorylation of a 185 kDa protein. In the presence of stimulatory concentrations of HRG, a blocking monoclonal antibody (2C4) to p185erbB2 is capable of significantly inhibiting phosphorylation of a 185 kDa protein as well as the subsequent incorporation of 3H-thymidine within the human SC. These latter results implicate an important role for p185erbB2 in mediating the mitogenic response of human SCs to HRGs. PMID- 7869102 TI - Postnatal development of GABAA receptor function in somatosensory thalamus and cortex: whole-cell voltage-clamp recordings in acutely isolated rat neurons. AB - GABAergic inhibition synchronizes oscillatory activity in the thalamocortical system. To understand better the role of this neurotransmitter in generation of thalamocortical rhythmicity, the postnatal development of GABAergic function mediated through activation of GABAA receptors was studied in thalamus and cortex. GABA-evoked chloride currents were recorded in dissociated rat cortical and thalamic neurons during postnatal development. Kinetic fits of GABA concentration/response relationships revealed developmental and regional alterations in the potency of GABA. Early in postnatal development (p5-p8), both thalamic and cortical neurons exhibited reduced potency of GABA (27-31 microM KD). Potency increased by p18-p25 in thalamic and cortical neurons (19-22 microM KD), to a level maintained in adult thalamic neurons. Adult cortical neurons exhibited reduced potency of GABA (40 microM KD). Benzodiazepine modulation of GABAA currents was also studied. Kinetic analyses of benzodiazepine augmentation of GABAA currents were best fitted assuming two effective sites with different affinities for clonazepam. The high-affinity site (KD of 0.05-0.27 nM) showed little variation with development in cortical neurons, contributing about 16-23% potentiation at all postnatal ages. Developing thalamic neurons (p5-p25) showed similar potency and efficacy of the high-affinity benzodiazepine site to cortical neurons. High-affinity benzodiazepine effects disappeared in adult thalamic neurons. A lower-affinity benzodiazepine site (25-50 nM KD) was greater in efficacy in cortical neurons compared to thalamic neurons at all ages, with efficacy ranging from 50% to 110% in cortex and from 20% to 60% in thalamus. Knowledge of developmental and regional alterations in GABAA receptor function may aid in understanding mechanisms involved in generation and control of normal and pathological thalamocortical rhythms. PMID- 7869103 TI - The CNS-specific hyaluronan-binding protein BEHAB is expressed in ventricular zones coincident with gliogenesis. AB - Hyaluronan (HA) is a ubiquitous component of extracellular matrices, and in several systems it plays a central role in regulating cellular proliferation and differentiation. Cell, or tissue,-specific functions of HA are likely to be mediated by cell, or tissue,-specific HA-binding proteins. We previously hyaluronan-binding protein from rat and cat (Jaworski et al., 1994). In view of the potential role of HA in neural differentiation, we examined the expression of BEHAB during late embryonic and early postnatal development of the rat. BEHAB is expressed at very high levels in ventricular zones throughout the neuraxis. Expression is first detected at embryonic day 15 (E15) in the spinal cord, and is detected at progressively more rostral levels at later ages. BEHAB expression, like other features of neural development, follows both caudal-to-rostral and ventral-to-dorsal gradients. The timing of BEHAB expression parallels the timing of the generation of glial cells. In all areas of the CNS examined, BEHAB expression begins after the peak of neurogenesis and coincident with gliogenesis. The regulation of proliferation and differentiation by HA in other tissues, together with the expression of BEHAB in zones of mitotic activity coincident with the generation of glia, suggests that the extracellular matrix protein encoded by BEHAB could play a role in the generation or differentiation of CNS glia. PMID- 7869104 TI - Expression of neuronal acetylcholine receptor genes in vertebrate skeletal muscle during development. AB - Of the 15 nicotinic ACh receptor genes identified in vertebrates, only four (alpha 1, beta 1, gamma, and delta) have been shown to be expressed in embryonic skeletal muscle at early times. In mammalian muscle a fifth gene (epsilon) replaces the gamma gene in expression at later times. The remaining 10 nicotinic receptor genes identified to date (alpha 2-alpha 8, beta 2-beta 4) are expressed in the nervous system and are considered neuronal genes. Using RNase protection assays, we show here that four of the neuronal-type genes (alpha 4, alpha 5, alpha 7, and beta 4) are expressed in developing chick skeletal muscle. Two of them (alpha 4 and alpha 7) decline substantially in transcript abundance between embryonic days 11 and 17, as does alpha 1, while the other two (alpha 5 and beta 4) show only moderate decreases over the same time period. At embryonic day 8, alpha 7 transcripts are nearly 20% as abundant as alpha 1 transcripts. In situ hybridizations confirm the presence of alpha 7 transcripts in muscle cells both in cell culture and in embryonic tissue. No evidence was found for expression of the alpha 2, alpha 3, alpha 8, or beta 3 genes in muscle. Immunoprecipitations and immunoblot analysis using subunit-specific monoclonal antibodies reveal alpha 7 protein in muscle, and the amount of protein rises and declines with the amount of alpha 7 mRNA during development. Sucrose gradient analysis demonstrates that the alpha 7 protein is present in muscle as a species of 10S, the size expected for a nicotinic receptor. The alpha 7 species in muscle binds alpha-bungarotoxin but does not contain alpha 1 subunits, indicating that the two kinds of alpha type gene products segregate during assembly. The results suggest that neuronal AChRs may play a role in early muscle development. PMID- 7869105 TI - Differential modulation by sulfhydryl redox agents and glutathione of GABA- and glycine-evoked currents in rat retinal ganglion cells. AB - Some areas of the mammalian CNS, such as the retina, contain not one but two fast inhibitory neurotransmitter systems whose actions are mediated by GABA and glycine. Each inhibitory receptor system is encoded by a separate gene family and has a unique set of agonists and antagonists. Therefore, in rat retinal ganglion cells we were surprised to find that a single agent, extracellular glutathione, was capable of modulating currents activated by either GABAA or glycine receptor stimulation. Both oxidized and reduced glutathione influence inhibitory neurotransmission in a manner similar to that of the sulfhydryl redox agents dithiothreitol (DTT) and 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB). Remarkably, the actions of glutathione are diametrically opposed on the GABAA and glycine systems. In whole-cell recordings of single retinal ganglion cells with patch pipettes, reduced glutathione enhances GABA-evoked currents but decreases glycine-evoked currents. These findings suggest that endogenous redox agents, such as glutathione, may constitute a novel modulatory system for the differential regulation of inhibitory neurotransmission in the mammalian retina. PMID- 7869106 TI - Optical signals from neurons with internally applied voltage-sensitive dyes. AB - We carried out experiments to monitor optically the generation and spread of action potentials and subthreshold potentials in the processes of individual neurons in ganglia of the snail, Helix aspersa. The neurons were selectively stained by intracellular pressure injection of voltage-sensitive dyes. Optical signals were detected by a system for fast, multiple-site optical monitoring, utilizing a silicon photodiode array. After testing 30 voltage-sensitive dyes using absorption, we concluded that this mode was probably not sensitive enough to allow monitoring neuronal signals from distal processes. Satisfactory signals were obtained in fluorescence measurements using a newly synthesized styryl dye, JPW1114, specifically designed for intracellular application. There was an improvement in sensitivity (as defined by the signal-to-noise ratio) by a factor of about 50 over previously reported absorption and fluorescence signals from neuronal processes stained by either intra- or extracellular application of dyes. Recordings with good signal-to-noise ratio and adequate spatial and temporal resolution were obtained simultaneously from the cell body and long axonal branches. From this data, the site of action potential initiation was determined. Also, the propagation velocity of the action potential was calculated for different axonal segments; the results suggest that different regions have different velocities ranging from 0.53 m/sec to 0.07 m/sec. The present sensitivity was adequate to allow the recording of a 10 mV hyperpolarizing electrotonic response along axonal branches and to observe directly the decline of this passive response with distance from the site of stimulation. Relatively modest improvements in sensitivity will allow systematic analyses of the spread and summation of synaptic potentials in individual neurons. PMID- 7869107 TI - Functional expression of Shaker K+ channels in cultured Drosophila "giant" neurons derived from Sh cDNA transformants: distinct properties, distribution, and turnover. AB - Expression of transgenic Shaker (Sh) channels has not previously been examined in Drosophila neurons. We studied K+ current by whole-cell recording in cultured "giant" neurons derived from germline transformants. Independent lines were generated by using a P-element vector, in which transcription of the 29-4 cDNA, one of the Sh splicing variants (Iverson and Rudy, 1990), was under the control of a heat shock (HS)-inducible promoter. Transformants in wild-type and two different Sh mutant backgrounds all exhibited an HS-inducible, A-type K+ current that was characterized by a much slower recovery from inactivation and a higher sensitivity to 4-aminopyridine than native K+ currents of Sh 29-4 currents expressed in Xenopus oocytes. Despite similarities in the kinetic and pharmacological properties of the HS-induced current in all backgrounds examined, host-dependent differences in the peak current amplitude have been consistently observed between multiple lines of 29-4 ShM and 29-4 Sh120 that might reflect differential channel subunit assembly in different hosts. Isolation of the novel 29-4 currents allowed determination of the channel turnover rate in cultured neurons. These currents persisted for up to 3 d or more, comparable with the durations previously reported for Na+ and Ca2+ channels. Surprisingly, the percentage of cells expressing inactivating K+ currents remained approximately the same with or without HS induction, suggesting that some mechanisms exist to restrict functional expression of inactivating K+ channels, including transgenic Sh channels and those not encoded by the Sh locus, to certain types of neurons. PMID- 7869108 TI - Acetylcholine-induced retraction of an identified axon in the developing leech embryo. AB - At early stages of embryonic development of the glossiphoniid leech, Theromyzon rude, a branch, termed MAC, of the axon of the segmentally iterated Retzius neuron extends into the anterior interganglionic connective nerve. At later stages, this branch disappears again in about 30% of the Retzius neurons in the standard midbody segments and in about 75% of the Retzius neurons in the two reproductive midbody segments. The frequency of disappearance of the MAC branch increases to about 85% in all Retzius neurons upon exposure of the embryos to culture media containing 1 mM acetylcholine (ACh) and 10 microM physostigmine during a sensitive period of axon outgrowth. This disappearance represents a retraction of the MAC branch to its point of origin, while other axon branches of the Retzius neuron remained unaffected. In later development, the retracted (medial) MAC branch was replaced by a new (lateral) branch termed LAC. The observations were made using confocal microscopy of fixed embryos stained with anti-5-HT antibody and confirmed by Lucifer yellow injection of individual Retzius neurons. The specific retraction of a single axon branch might be attributable to the local presence of extracellular matrix molecules in the ganglionic neuropil, which is contacted only by the MAC axon branch and could render this branch susceptible to growth-regulating signals. Since Retzius axon morphology in standard segments of ACh-treated embryos resembled that of reproductive segments in untreated embryos, it appears possible that ACh treatment may have simulated a process that contributes to the segmental differentiation of the Retzius neuron. PMID- 7869109 TI - Mamillothalamic tract transection blocks anterior thalamic training-induced neuronal plasticity and impairs discriminative offidance behavior in rabbits. AB - Rabbits with bilateral transecting lesions of the mamillothalamic tract, control (tract-sparing and sham) lesions, or no lesions, and chronic, fixed-position anterior ventral (AV) and medial dorsal (MD) thalamic and posterodorsal subicular complex unit recording electrodes were trained to step in an activity wheel in response to a 0.5 sec tone (CS+) in order to avoid a brief foot shock. The rabbits also learned to ignore a different tone (CS-) not predictive of shock. Behavioral acquisition was significantly retarded in rabbits with mamillothalamic tract transection compared to controls. When trained, transected rabbits failed to avoid the shock more often than controls. Mamillothalamic tract transection abolished and control lesions attenuated AV thalamic discriminative training induced activity (i.e., development with training of greater discharges in response to the CS+ than to the CS-). Transection and control lesions attenuated AV thalamic excitatory training-induced activity (greater elicited activity during training than during unpaired tone-shock presentations before training) as well as AV thalamic "spontaneous" baseline unit activity. CS-elicited discharge magnitude was reduced by control lesions and it was further reduced by tract transecting lesions. Significant lesion-related changes were not found in the subicular or MD thalamic neuronal receptor. Mamillothalamic tract afferent information flow is thus essential for AV thalamic discriminative training induced activity, excitatory training-induced activity, tone-elicited discharges and maintenance of conditioned avoidance responses. The effects of the control lesions suggested that afferents which course in parallel with and near the mamillothalamic tract may contribute to AV thalamic spontaneous activity and excitatory training-induced activity. PMID- 7869111 TI - Analysis of connectivity in the cat cerebral cortex. AB - The mammalian cerebral cortex is innervated by a large number of corticocortical connections. The number of connections makes it difficult to understand the organization of the cortical network. Nonetheless, conclusions about the organization of cortical systems drawn from examining connectional data have often been made in a speculative and informal manner, unsupported by any analytic treatment. Recently, progress has been made toward more systematic ways of extracting organizing principles from data on the network of connections between cortical areas of the monkey. In this article, we extend these approaches to the cortical systems of the cat. We collated information from the neuroanatomical literature about the corticocortical connections of the cat. This collation incorporated 1139 reported corticocortical connections between 65 cortical areas. We have previously used an optimization technique (Scannell and Young, 1993) to analyze this database in order to represent the connectional organization of cortical systems in the cat. Here, we report the connectional database and analyze it in a number of further ways. First, we employed rules from Felleman and Van Essen (1991) to investigate hierarchical relations among the areas. Second, we compared quantitatively the results of the optimization method with the results of the hierarchical method. Third, we examined quantitatively whether simple connection rules, which may reflect the development and evolution of the cortex, can account for the experimentally identified corticocortical connections in the database. The results showed, first, that hierarchical rules, when applied to the cat visual system, define a largely consistent hierarchy. Second, in both auditory and visual systems, the ordering of areas by hierarchical analysis and by optimization analysis was statistically significantly related. Hence, independent analyzes concur broadly in their ordering of areas in the cortical hierarchies. Third, the majority of corticocortical connections, and much of the pattern of connectivity, were accounted for by a simple "nearest-neighbor-or-next door-but-one" connection rule, which may suggest one of the mechanisms by which the development of cortical connectivity is controlled. PMID- 7869110 TI - Facilitation of acetylcholine release and cognitive performance by an M(2) muscarinic receptor antagonist in aged memory-impaired. AB - Aged memory-impaired (AI) and unimpaired (AU) 24-25-month-old Long-Evans rats were used to investigate the integrity of various cholinergic markers during normal aging and to establish if alterations can possibly relate to cognitive disabilities. AI and AU rats were classified on the basis of their performance in the Morris swim maze task. Choline acetyltransferase activity (ChAT) was not differentially altered in various cortical and hippocampal areas between these two groups. Similarly, quantitative receptor autoradiography did not reveal significant differences in 3H-pirenzepine/muscarinic M1 and 3H-hemicholinium 3/high-affinity choline uptake binding sites in AI versus AU rats. In contrast, 3H-AF-DX 384/putative muscarinic M2 binding was significantly increased in certain cortical and hippocampal areas of the age-impaired animals. These increments were correlated with decreased in vivo acetylcholine (ACh) release capacity in the AI rats. Most interestingly, the muscarinic M2 antagonist BIBN-99 reversed, in a dose-dependent manner, the impaired ACh release as well as the cognitive deficits observed in the AI group. Similarly, BIBN-99 reversed scopolamine-induced amnesia in young animals. The efficacy of BIBN-99 likely relates to its antagonistic properties on negative muscarinic M2 autoreceptors that are apparently increased in the AI animals, leading to altered ACh release. Taken together, these findings strengthen the role of ACh in learning and memory and may have implications for the treatment of degenerative disorders associated with impaired cholinergic functions, such as Alzheimer's disease. PMID- 7869113 TI - Two kinetically distinct 5-hydroxytryptamine-activated Cl- conductances at Retzius P-cell synapses of the medicinal leech. AB - The properties of serotonin (5-HT)-activated Cl- receptor/ion channel complexes in neurons of the CNS of the medicinal leech were analyzed. These channels mediate the postsynaptic response at the serotoninergic Retzius P-cell as well as Retzius-Retzius cell synapses. 5-HT-induced Cl- currents were activated by fast superfusion of transmitter on cells dissociated from embryonic leeches including histochemically identified Retzius cells. Whole-cell currents elicited by partial superfusion of the membrane and summated single-channel currents of outside-out patches showed times to peak of 18 +/- 4 msec and 10 +/- 5 msec, respectively, and desensitized with time constants of 28 +/- 3 msec and 20 +/- 11 msec. Persistence of single-channel openings in the outside-out configuration as well as lack of effect of dialysis of the whole cell with AMP-PNP or GDP-beta-S indicated that 5-HT directly gates the Cl- channels without involving second messenger cascades. In outside-out patches, two single-channel conductances of 13 pS and 32 pS were identified. While the 13 pS conductance desensitized, the 32 pS conductance activated within several tens of msec and showed no desensitization. We postulate that two subtypes of channels are coactivated by 5-HT and that the activation of the fast desensitizing channel could be responsible for the fast decaying component of the post-synaptic response. The slow conductance explains the second slower decay time constant of the postsynaptic response and could account for the tonic component sometimes observed at Retzius P-cell synapses. PMID- 7869112 TI - Decreased monosynaptic sensory input to an identified motoneuron is associated with steroid-mediated dendritic regression during metamorphosis in Manduca sexta. AB - The proleg withdrawal reflex of Manduca sexta larvae is mediated by mono- and polysynaptic connections from afferents innervating mechanosensory planta hairs (PHs) to ipsilateral proleg retractor motoneurons. During the larval-pupal transformation, a rise in ecdysteroids causes the dendrites of proleg motoneurons to regress and, concurrently, the proleg withdrawal reflex is lost. The objective of this study was to identify synaptic correlates of dendritic regression that contributed to this behavioral change. The accessory planta retractor (APR) motoneuron regresses during the larval-pupal transformation and dies in a segment specific pattern after pupation. The compound excitatory postsynaptic potential (cEPSP) evoked in APR by electrically stimulating the proleg sensory nerve decreased in amplitude during the larval-pupal transformation. The developmental decrease in cEPSP amplitude, the extent of APR's regression, and several of APR's intrinsic electrical properties were similar in segments in which the motoneuron was fated to live or die. In heterochronic mosaic pupae bearing retained larval PH afferents, APR's dendritic regression was associated with decreases in both the mean amplitude of monosynaptic EPSPs produced by PH afferents and the proportion of PH afferents that produced detectable EPSPs. These changes appeared due to a developmental decrease in the size of the synaptic currents produced by PH afferents. Evidence was also obtained suggesting that PH afferents do not regress at pupation. These findings support the hypothesis that the ecdysteroid mediated regression of proleg motoneuron dendrites disconnects them from sensory inputs and, thereby, contributes to the elimination of the proleg withdrawal reflex. PMID- 7869114 TI - Interactions during a critical period inhibit bilateral projections in embryonic neurons. AB - The anterior pagoda (AP) neurons in the CNS of the medicinal leech are found as homologous pairs in 20 of the 21 midbody ganglia. Each AP is the mirror image of its mate, extending its main axon across the midline of the CNS and eventually into the contralateral body wall, thereby attaining a unilateral pattern of innervation. Certain features of the adult AP morphology are known to arise through interactions among homologs early in development (Gao and Macagno, 1987b), but it is not known whether the contralateral nature of the projection pattern is due to intrinsic "one-sidedness" or rather to cell-cell interactions that inhibit the formation of a second, ipsilateral projection. In the experiments described in this report, we tested the possibility that an AP's contralateral homolog itself inhibits the formation of bilateral projections. One AP was photoablated in the intact embryo early in development and then the response of the remaining AP was examined. We found that an AP can extend bilaterally symmetrical projections when its homolog is missing, but only during a critical period that, interestingly, begins when an AP's interactions with other specific neurons come to an end. To determine whether synaptic communication between AP homologs could be responsible for the timing of this critical period, we recorded electrophysiologically from pairs of embryonic AP neurons. Although no detectable chemical signaling was observed, AP cells were electrically coupled throughout the entire critical period. Further, the junctions between these neurons were permeated by 5-HT, whereas larger molecules such as carboxyfluorescein were impermeant. This dye coupling decreased with age even while electrical coupling persisted, suggesting but not proving that the properties of the gap junctions between AP neurons may also change with time. We conclude that unilateral AP cells possess the intrinsic ability to project bilaterally, but are inhibited from doing so by age-dependent interactions with homologous neurons, possibly mediated by gap-junctional communication. PMID- 7869115 TI - NMDA-receptor antagonists disrupt the formation of the auditory space map in the mammalian superior colliculus. AB - In the ferret (Mustela putorius) the map of auditory space in the deeper layers of the superior colliculus (SC) matures over a period of several postnatal weeks, a process known to be guided by both visual and auditory experience. The auditory responses are initially very broadly tuned, and gradually become more selective for specific sound locations that coincide with the visual receptive fields recorded in the same region of the SC. To investigate the possible involvement of NMDA-type glutamate receptors in the postnatal development of this auditory representation, we have reared ferrets in which 400 microns thick sheets of the slow-release polymer Elvax, containing the NMDA receptor antagonists MK801 or APV, were placed on the dorsal surface of the SC. The Elvax was implanted on postnatal day (P) 25-27, just before the onset of hearing, and removed 5-6 weeks later, just prior to recording from the SC on around P61-70. In vitro measurements with Elvax containing 3H-MK801 revealed that the amount of drug released declined sharply over the first 10 d and then stabilized at a fairly constant rate for the following 5 weeks. These in vitro data were found to parallel the in vivo release of MK801 from implanted Elvax slices. Diffusion of MK801 from the implant was measured and significant levels were found within 800 microns of the SC surface, suggesting that the action of MK801 was restricted to the superficial and intermediate layers of the nucleus. Extracellular recordings were made from visual and auditory units in the SC in response to free-field stimulation. The visual responses of units recorded in the superficial layers appeared to be unaffected by either of the drug treatments, and formed a normal, adult-like map of visual azimuth along the rostrocaudal axis of the SC in all animals. Most of the auditory single-unit responses recorded at this age in normal, unoperated controls were spatially tuned and topographically organized, although the map of sound azimuth was less precise than that in adult ferrets. Data from age-matched control animals that had been reared with drug-free Elvax implants were not statistically different from the unoperated juvenile ferrets. However, in animals reared with APV or MK801 Elvax implants, there was an increase in the relative numbers of auditory units that were ambiguously tuned to two or more locations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7869116 TI - Cellular and molecular characterization of a brain-enriched protein tyrosine phosphatase. AB - Regional variations in the expression of a striatal enriched protein tyrosine phosphatase called STEP were studied in the adult rat brain by a combination of immunocytochemistry, lesion studies, Western blotting, and in situ hybridization. Monoclonal antibodies generated against STEP identified multiple polypeptides of M(r) 46, 37, 33 and a doublet of M(r) 64-66 kDa on Western blots. Although the three STEP immunoreactive bands with lower molecular weights were enriched in cytosolic fractions, the 64-66 kDa doublet was enriched in membrane fractions. All of the immunoreactive forms were abundant in the caudate-putamen and were present in lower amounts or were undetectable in other brain regions. In substantia nigra, the M(r) 64-66 kDa doublet was not detected but bands with M(r) 46, 37, and 33 kDa were present. Immunocytochemical and lesion experiments demonstrated that the cytosolic STEP isoforms present in the substantia nigra are in presynaptic axons originating from the projection neurons of the caudate putamen, which innervate this structure. Additional in situ hybridization studies showed that STEP mRNA expression patterns correlate with the patterns of immunocytochemical staining. These findings indicate that there are multiple polypeptide isoforms of STEP enriched in the basal ganglia and related structures which differ in terms of their intracellular locations and functional roles. PMID- 7869117 TI - Sensory neurons selectively upregulate synthesis and transport of the beta III tubulin protein during axonal regeneration. AB - The effects of peripheral nerve injury on the content, synthesis, and axonal transport of the class III beta-tubulin protein in adult rat dorsal root ganglion (DRG) neurons were examined. Recent reports of selective increases in the steady state levels of the beta III-tubulin mRNA during axonal regeneration (Moskowitz et al., 1993) led to the hypothesis that upregulated levels of expression of the beta III-tubulin isotype that alter the composition of neuronal microtubules is important for effective axonal regrowth. If this is the case, the increases in mRNA levels must be translated into increased beta III-tubulin protein levels and subsequently modify the axonal cytoskeleton via axonal transport mechanisms. The present study assessed whether or not this occurs by examining beta III-tubulin protein content in adult rat lumbar DRG neurons at different times (1-14 d) after a distal sciatic nerve crush (approximately 55 mm from the DRG) by Western blotting and immunocytochemistry with a beta III-tubulin specific monoclonal antibody. These studies showed substantial increases in beta III-tubulin content in DRG neurons, as well as in proximal regions of peripheral sensory axons (0-6 mm from the DRG), from 1-2 weeks after a distal nerve injury. Pulse labeling of DRG neurons with 35S-methionine and 35S-cysteine and immunoprecipitation of labeled beta III-tubulin indicated that the synthesis of beta III-tubulin was increased in the DRG after axotomy. Studies of axonal transport, wherein L5 DRG proteins were labeled with 35S-methionine and 35S-cysteine by microinjection, revealed that slow component b(SCb) of axonal transport conveyed more labeled tubulin moving at apparently faster rates through the intact regions of sciatic nerve axons in response to crush injury of the distal sciatic nerve. Immunoprecipitation experiments using proximal peripheral nerve segments showed that SCb in distally injured DRG neurons was enriched in the beta III-tubulin isotype. These findings demonstrate that the augmented synthesis of beta III tubulin after axotomy alters the composition of the axonally transported cytoskeleton that moves with SCb. The increased amounts and rate of delivery of beta III-tubulin in axons of regenerating DRG neurons suggest that the altered pattern of tubulin gene expression that is initiated by axotomy impacts on the composition and organization of the axonal cytoskeleton in a manner that can facilitate axonal regrowth. PMID- 7869119 TI - GABAergic and developmental influences on homosynaptic LTD and depotentiation in rat hippocampus. AB - Low-frequency (1 Hz) stimulation (LFS) was used to elicit long-term depression (LTD) or depotentiation of excitatory transmission of the Schaffer collateral pathway in the CA1 region of the rat hippocampus. Both LTD and depotentiation were found to be homosynaptic and NMDA receptor (NMDAR) dependent. As NMDAR activation can be modulated by the inhibitory GABAergic system, we tested the hypothesis that GABA plays a role in regulating these phenomena. The GABAB antagonist CGP 35348 significantly inhibited LTD, but not depotentiation, in slices from young animals (indicating that the GABAB-mediated contribution was altered following HFS). The ability to express LTD was found to be developmentally dependent, as young animals (16-22 d) consistently expressed LTD, whereas LTD was not expressed in naive slices taken from mature (5-10 weeks) animals. The GABAA antagonist bicuculline did not affect LTD in the young animals, but did enhance LTD expression in slices from mature animals. LFS was also effective in decreasing, or depotentiating, responses that had undergone long-term potentiation (LTP) by high-frequency stimulation (HFS). In contrast to LTD, depotentiation was consistently expressed in slices from both the young and mature groups. Moreover, following an HFS train, LTD (compared to initial baseline response) could be induced in mature slices previously unable to express LTD in the naive state. Thus, the role of GABA in modulating the effects of LFS varied with the prior synaptic activity in the slice as well as with the maturity of the animal. Our results suggest that the influence of both age and prior synaptic activity (i.e., HFS) on LTD induction can be explained by changes in GABAergic systems in young versus mature, and naive versus tetanized slices. PMID- 7869120 TI - The dendritic lamellar body: a new neuronal organelle putatively associated with dendrodendritic gap junctions. AB - It is shown in rat that antiserum alpha 12B/18 specifically labels a new lamellar organelle that is exclusively located in dendritic appendages. These dendritic lamellar bodies occur in a restricted number of brain regions, which include areas like the inferior olive, area CA1 and CA3 of the hippocampus, dentate gyrus, olfactory bulb, and cerebral cortex. In these regions the neurons with lamellar bodies form dendrodendritic gap junctions. Immunoreactivity in the inferior olive is first detected between P9 and P15, which coincides with the development of gap junctions in this nucleus. In the adult inferior olive, the density of dendritic lamellar bodies is highest in the rostral medial accessory olive, the subnucleus where electrotonic coupling is most prominent. Antiserum alpha 12B/18, thus, specifically detects a new neuronal organelle that may be related to dendrodendritic gap junctions. PMID- 7869118 TI - TrkA expression in the CNS: evidence for the existence of several novel NGF responsive CNS neurons. AB - NGF acts as a neurotrophic factor by binding and activating its receptor on certain neuronal populations in the CNS and PNS. TrkA is a receptor for NGF. Recent findings in vitro indicate that this NGF-activated receptor tyrosine kinase transduces the NGF signal. To further define NGF actions in the CNS, we examined trkA expression in the adult rat brain. We found that trkA mRNA and immunoreactivity (IR) coincided in specific, defined neuronal populations in the forebrain and brainstem. In addition to cholinergic neurons in the basal forebrain and neostriatum, trkA expression was found in noncholinergic neurons in (1) the paraventricular anterior and reuniens thalamic nuclei, (2) the rostral and intermediate subnuclei of the interpeduncular nucleus (IPN), (3) scattered neurons in the ventrolateral and paramedian medulla, (4) the prepositus hypoglossal nucleus, and (5) the area postrema. NGF responsiveness was demonstrated for each of these populations. In contrast to trkA, p75NGFR was found only in a minority of NGF-responsive populations. Our data provide further evidence that expression of trkA marks NGF-responsive CNS neurons and suggests novel roles for NGF in the brain. PMID- 7869121 TI - The neurophysiology of figure-ground segregation in primary visual cortex. AB - The activity of neurons in the primary visual cortex of the awake macaque monkey was recorded while the animals were viewing full screen arrays of either oriented line segments or moving random dots. A square patch of the screen was made to perceptually pop out as a circumscribed figure by virtue of differences between the orientation or the direction of motion of the texture elements within that patch and the surround. The animals were trained to identify the figure patches by making saccadic eye movements towards their positions. Almost every cell gave a significantly larger response to elements belonging to the figure than to similar elements belonging to the background. The figure-ground response enhancement was present along the entire extent of the patch and was absent as soon as the receptive field was outside the patch. The strength of the effect had no relation with classical receptive field properties like orientation or direction selectivity or receptive field size. The response enhancement had a latency of 30-40 msec relative to the onset of the neuronal response itself. The results show that context modulation within primary visual cortex has a highly sophisticated nature, putting the image features the cells are responding to into their fully evaluated perceptual context. PMID- 7869122 TI - Regionalization of the developing forebrain: a comparison of FORSE-1, Dlx-2, and BF-1. AB - The FORSE-1 monoclonal antibody (mAb) was generated using a strategy designed to produce mAbs against neuronal cell surface antigens that might be regulated by regionally restricted transcription factors in the developing CNS. To determine whether FORSE-1 has a labeling pattern similar to that of known transcription factors, the expression of BF-1 and Dlx-2 was examined by in situ hybridization on sections serial to those labeled with FORSE-1. We find a striking overlap between BF-1 and FORSE-1 in the telencephalon; both are expressed in the lateral but not the medial walls of the telencephalon, and the boundaries of expression are apparently identical. FORSE-1 staining is detected prior to BF-1 expression in the neural tube, however. FORSE-1 and Dlx-2 have very different patterns of expression in the forebrain, suggesting that regulation by Dlx-2 cannot by itself explain the distribution of FORSE-1. However, they share some sharp boundaries in the diencephalon. In addition, FORSE-1 identifies some previously unknown boundaries in the developing forebrain. These results indicate that a new cell surface marker can be used to subdivide the embryonic telencephalon and diencephalon into regions smaller than previously described, providing necessary complexity to the developmental patterning in the forebrain. PMID- 7869123 TI - Motility and cytoskeletal organization of migrating cerebellar granule neurons. AB - To characterize CNS neuronal precursor migration along astroglial fibers, we examined the motility of the migratory leading process and cytoskeletal-based mechanisms of locomotion of early postnatal mouse cerebellar granule neurons in vitro. To visualize the surface motility of the leading process, granule neurons were labeled with the fluorescent lipophilic dye, PKH-26, and imaged by time lapse fluorescence microscopy. The motile behavior and cytoskeletal organization of the migrating neuron had several distinctive features. As the migrating neuron moved along the glial fiber, the leading process rapidly extended, projecting up to 40 microns, and retracted, withdrawing towards the cell soma. Broad lamellipodia were common along the entire length of the leading process, giving it a ruffled appearance. Within the cell soma, a cage-like distribution of microtubules encircled the nucleus and actin filaments formed a subcortical rim underneath the plasma membrane. Disruption of actin filaments with cytochalasin B inhibited migration, suggesting involvement of actin subunit assembly in neuronal migration. Both microtubules and actin filaments were heavily concentrated in the leading process; the leading process did not show the development of a distinct actin-rich domain at its tip. PMID- 7869124 TI - Soluble factors from the olfactory bulb attract olfactory Schwann cells. AB - Olfactory Schwann cells (OSCs) extend processes that ensheathe bundles of olfactory axons as they course from the olfactory epithelium to the olfactory bulb (OB). Results of morphological and immunohistochemical studies have led to speculation that OSCs may be involved in guiding the olfactory axons to their target tissue. In this study we have explored this possibility by investigating the relationship between OSCs and the OB. Olfactory Schwann cells labelled with 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) were injected into the nasal region of E14 rat embryos and entire embryos were cultured for 24 hr. It was found in some embryos, that the OSCs had migrated toward the presumptive OB. Cocultures of neonatal OB explants on OSC monolayers showed that the OSCs were attracted to the OB and formed a ring-like aggregate around the explant after 48 hr culture. This attraction was absent when a piece of cerebrum was used in place of the OB. When medium conditioned by neonatal OBs was placed in the lower compartment of the chemotaxis chamber, OSCs seeded in the upper compartment migrated through the pores of the nucleopore filter to reach the underside which was in contact with the conditioned medium. After 6 hr of incubation, scanning electron microscopy was performed on the underside of the nucleopore filters. Cell counts of OSCs showed that the cell density was significantly higher when medium conditioned by OBs was used instead of unconditioned medium or medium conditioned by cerebrum. The results of these experiments show that the OSCs migrate toward the OB under the influence of soluble factor(s) secreted by the target tissue. PMID- 7869125 TI - Amphiphilic property of chlorhexidine and its toxicity against Streptococcus mutans GS-5. AB - The toxicity of chlorhexidine digluconate against Streptococcus mutans GS-5 was comparatively determined by measuring its bactericidal activity, and its inhibitory effect on microbial dehydrogenases was studied by the resazurin reduction method. Both methods indicated that chlorhexidine within the range 0.75 5.00 mg/l was highly toxic to Streptococcus mutans, probably due to inhibition of dehydrogenase activity, and the extent of toxicity was closely associated with concentration. In an attempt to better understand the relationship between the amphiphilic nature of chlorhexidine and its toxicity against Streptococcus mutans, the effect of solvent polarity on dehydrogenase inhibition was investigated. A decrease in solvent polarity, induced by inclusion of 5% acetone in the reaction mixture, did not enhance the toxicity of chlorhexidine. This implies that the antimicrobial action of chlorhexidine is mainly attributable to its hydrophilicity, and that the nature of the lipophilic groups is only of secondary importance. PMID- 7869126 TI - The effects of cervical headgear on dentofacial structures. AB - A study was made on the effects of cervical headgear on dentofacial structures, especially non-erupted teeth, in the early and late mixed dentition periods. Pretreatment and post-treatment cephalometric evaluation was done on 8 patients in the early mixed dentition period and 10 patients in the late mixed dentition period. The results showed that any reference line passing through Ptm point should not be used to evaluate the efficiency of cervical headgear, and that such headgear is more effective on non-erupted teeth in early mixed dentition. PMID- 7869127 TI - Concentrations of thiocyanate and hypothiocyanite in the saliva of young adults. AB - The study was conducted to determine thiocyanate (SCN-) and hypothiocyanite (OSCN ) concentrations in resting (RWS) and stimulated whole saliva (SWS) and stimulated parotid saliva (SPS) of 20 healthy young adults aged 21-29 y. Samples of saliva were collected at 12:30, immediately before lunch. Resting saliva was collected by expectoration, and stimulated saliva was collected during the uniform chewing of paraffin wax. Parotid secretion was collected using a modified Carlsson-Crittenden cup (Carlsson et al., Am, J. Physiol., 26, 169-177, 1910). SCN- concentration was determined by the ferric nitrate method (Betts et al., J. Am. Chem. Soc., 75, 5721-5727, 1953) whilst OSCN- was assayed using 2 mercaptoethanol as a reducing agent (Pruitt et al., Caries Res., 16, 315-323, 1982). In RWS, SWS and SPS, the mean SCN- concentrations (in mM) were 1.48 +/- 0.59(S.D.), 0.90 +/- 0.56(S.D.) and 1.24 +/- 0.65(S.D.) whilst the mean OSCN- concentrations (in microM) were 31.21 +/- 13.54(S.D.), 24.90 +/- 12.61 and 30.19 +/- 23.35(S.D.) in the respective salivas. The presence of OSCN- in the secretion collected from the parotid gland supported previous findings by Tenovuo and Pruitt (Tenovuo et al., J. Oral Path, ol. 13, 573-584, 1984), who suggested an endogenous glandular (eukaryotic) source of hydrogen peroxide (H2O2), since parotid saliva from healthy glands is devoid of bacteria and leukocytes. PMID- 7869128 TI - Evaluation of surface smoothness detected by a periodontal probe. AB - An investigation was designed to determine whether or not the required smoothness has been reached. This is still a controversial subject among clinicians. Ten cylindrical metal samples of equal sizes with various degrees of smoothness were prepared, and their degrees of smoothness were assessed in a blind manner by 14 periodontists, who were asked to group them as smooth or rough using a periodontal probe. Along with the metal samples, the roughness of root surfaces smoothed in clinics was also evaluated using a Profilometer. The average value defined as a smooth surface on a max.-min. scale was 1.86 +/- 0.42, and values above 3.57 were considered to be rough. Consequently, decisions taken using the sense of touch about the smoothness of a surface were confirmed to be reliable for clinical use. PMID- 7869129 TI - Effect of mercury from dental amalgams on mercury concentration in urine. AB - A study was conducted to determine the mercury concentration in urine after placement of dental amalgam restorations. The 24-h urine mercury levels in 10 children with a mean age of 8 years were determined before the amalgam restorations had been placed, and after placement. The urinary mercury content was measured by the cold vapor atomic fluorescence method. Mercury levels in the urine samples before placement of the amalgam restorations were below the detection limit, and the values obtained after placement, although detectable, were far below the limits stipulated by the World Health Organization. Under the conditions of this study, it is considered that the mercury levels released from dental amalgams are not high enough to cause any systemic toxic effect. PMID- 7869130 TI - Study of hereditary trends in the shape of the murine mandible. AB - Inbred mice are a suitable material for genetic studies, and mandibular shape in particular provides a highly quantitative hereditary trait. We investigated which genetic trait in F1, F2 and N2 hybrid mice was most strongly affected by the presence of a large or small mandible in the parents. Ten C57BL/6By strain mice as parents with a small mandible and 10 MRL/n strain mice as parents with a large mandible were employed. Twenty-five (C57BL/6By male X MRL/n female) F1 and 67 F2 hybrids, and 28 (F1 male X C57BL/6By female) N2 backcross hybrids were obtained by laboratory mating. The inter-landmarks of the right mandible were measured by an electronic digitizer. Each mean value of horizontal dimensions in F1 mice resembled that in MRL/l mice, and that in N2 mice was intermediate between C57BL/6By and MRL/n mice. On the other hand, the mean values of vertical dimensions in F1, F2 and N2 hybrids were intermediate between those of C57BL/6By and MRL/n mice. Hence we suggest that horizontal dimensions are predominantly inherited by mice with a large mandible, and that vertical dimensions show intermediate inheritance between mice with large and small mandibles in the C57BL/6By and MRL/n strains. PMID- 7869131 TI - Adsorption of salivary proteins to the surface of oral streptococcal cells. AB - Oral tissues, especially tooth surfaces, are covered with a layer of salivary proteins. Oral bacterial cells that adsorb to salivary components accumulated on the tooth surface are, as a rule, covered with the same components, especially proteins. Thus, it is possible that the salivary proteins covering the bacterial cells are related to the adhesion of bacteria to oral tissues. The aim of this study was to clarify the mechanisms of adsorption of salivary proteins to the surface of Streptococcus sanguis, S. mitis and S. salivarius using an adsorption assay with salivary proteins labeled with tritiated formaldehyde. The results showed that salivary proteins adsorbed more to S. salivarius than to S. mitis, and least to S. sanguis. It was evident that hydrophobic bonding was involved in the adsorption of salivary proteins to the bacterial cells tested. The amount of salivary proteins adsorbed to S. mitis and S. salivarius was decreased by the presence of phosphate, that to S. sanguis was increased by the presence of a divalent cation such as Ca2+, and that to all bacteria tested was inhibited in different ways by the presence of sugars. The amount of salivary proteins adsorbed to S. sanguis and S. salivarius was reduced effectively by pretreatment of the cells with trypsin, chymotrypsin and papain. In the case of S. mitis, the amount of adsorbed salivary proteins was decreased by pretreatment of the cells with chymotrypsin only, and was increased by pretreatment with lipase. These results indicate that there are different mechanisms of adsorption of salivary protein to the cell surfaces of oral streptococci. PMID- 7869132 TI - Albright's syndrome: review of the literature and case report. AB - Albright's syndrome is characterized by the presence of polyostotic fibrous dysplasia, endocrinopathies and brown spots on the skin. In the present article the authors describe a case occurring in a 20-year-old female patient, who is currently being followed radiographically after a mandibular bone biopsy. PMID- 7869133 TI - Storytelling: an innovative approach to staff development. AB - Using stories or narratives from clinical practice as a teaching/learning strategy is new in nursing education programs in hospitals. In this article, the authors describe three staff development programs using storytelling to enable others to use the interpretation of stories to promote expertise in clinical practice. PMID- 7869134 TI - Enhancing healthcare education with accelerated learning techniques. AB - In this article, the authors describe innovative teaching techniques that create a learning environment addressing nonverbal and verbal communication. The use of these accelerated learning techniques in a Basic Cardiac Dysrhythmia Course is discussed, and participant learning is measured and analyzed. When these methods, including relaxation, music, and subliminal messages were used, participant exam grades improved. The authors concluded that these simple procedures enhance learning and increase the effectiveness of teaching. PMID- 7869135 TI - The use of theory-based nursing practice in the Department of Veterans' Affairs Medical Centers. AB - In this study, the authors surveyed the chief nurses of 152 Veterans' Health Administration Medical Centers to determine which medical centers based their nursing practice on one or more nursing theories or models. Of the 76 medical centers responding, 24 (35%) stated theory-based practice was in use in their institutions. The greatest number (16 of the 24) reported use of Orem's Self-Care Deficit theory or a combination of Orem with other theories. Most of the 24 chief nurses agreed that theory-based practice: 1) improves patient outcomes; 2) maximizes patient health; and 3) provides a consistent approach to care. However, they were less convinced that theory-based practice reduces nursing staff turnover or improves job satisfaction. They also stated that theory-based practice is more important to nursing administrators than to staff nurses. A similar survey of staff nurses is recommended. PMID- 7869136 TI - Outcomes of a university-based registered nurse refresher course. A 5-year follow up. AB - Registered Nurse Refresher Courses are not uncommon in university, community college, and hospital settings. Most are costly to the organization in terms of money and human resources--especially when students choose not to practice once they have completed the course. In this study, the author reports the findings of a survey conducted on graduates of a university-based refresher course during a 5 year period. The issues include a retrospective evaluation of the course, mean age at the time of taking the course, time away from active practice before taking the course, number who returned to the workforce after the course, the number who left the workforce, and identification of respective clinical practice area. Statistical follow-up on the Registered Nurses completing the course and descriptors of personal frustrations, rewards, and overall concerns related to the refresher course are described in this article. PMID- 7869137 TI - Measuring satisfaction with patient education. A hospital-wide program evaluation. AB - Evaluation of patient education can provide important quality improvement information. In this article, the author describes the design and implementation of a family education satisfaction survey. Five components of patient education are evaluated, and differences in satisfaction with patient education between units and between diagnosis are measured. The results are used to recognize individual and unit excellence and identify opportunities for improvement. PMID- 7869138 TI - Implementing continued clinical competency evaluation in the emergency department. AB - Nurse educators are challenged with the task of assuring that those who practice emergency nursing do so with competence. Yet beyond entry level competency verification, few nurse educators have implemented programs documenting continued clinical competence. In this article, the authors describe a cost-effective, practical approach to designing a competency verification program. PMID- 7869139 TI - Come the reformation! PMID- 7869141 TI - Promoting professional communication. PMID- 7869140 TI - Making the most of nursing student projects: a collaborative pain management project. AB - A simple quality assurance project involving one facility and two nursing students provided an opportunity to meet the needs of the students, institution, nursing staff, and patients. Patients received more information on pain and pain management. Students met the objectives of their programs and also gained invaluable experience in research methods, education of staff members, and development of new policies. The facility capitalized on the findings of the original quality assurance study and used that information to make changes in the way pain was managed at the institution. This collaborative effort is just one example of the benefits that accrue when educational and clinical facilities work together. The challenge to education and practice is to work together to identify mutual goals and achieve objectives that meet educational and clinical needs. Not only can collaboration facilitate exceptional learning experiences for the student, it also can stimulate staff nurses' interest in research and lay the groundwork for education of staff to make changes in the way care is delivered. PMID- 7869142 TI - Downsizing: implications for nursing educators in a hospital setting. AB - In this article, the author describes the effects of downsizing on nurses, and more specifically, on continuing nurse educators in a tertiary care hospital. The author suggests strategies nurse educators can use to deal with their own vulnerabilities and to address the unique needs of nurses during downsizing. PMID- 7869143 TI - Stemming the tide of the global population explosion. The key role of women. PMID- 7869144 TI - Perineal outcomes and nurse-midwifery management. AB - This article describes the association among perineal outcomes, selected risk factors, and alternative intrapartum approaches used by nurse-midwives. This nonrandomized concurrent (cohort) study analyzed all spontaneous vaginal births (N = 1211) attended by nurse-midwives at a university hospital over a 2-year period. Univariate analysis was used to calculate relative risks for the associations between two perineal outcomes and selected variables. Study results indicated that parity, ethnicity, birth weight, and use of two techniques (hot compresses and lubrication) were associated with lacerations. The same factors that increase the risk of perineal lacerations also made the performance of an episiotomy more likely; however, for episiotomy, an inverse relationship with perineal hot compresses was noted, and perineal lubrication had no effect. Lack of perineal support was associated with a 66% rise in the risk of episiotomy. Use of birthing positions other than lithotomy significantly reduced the likelihood of episiotomy. The authors concluded that selected care measures to protect the perineum may reduce maternal morbidity and simplify intrapartum care. The risks and benefits of alternative strategies commonly used by nurse-midwives while caring for diverse populations during birth should be further evaluated in large multiethnic populations. PMID- 7869145 TI - Factors that predict performance on the national certification examination for nurse-midwives. AB - The ACNM Certification Council is responsible for determining that the national certification examination in nurse-midwifery is not biased toward any protected group. Educational programs of nurse-midwifery have an interest in knowing that their admissions criteria and educational design have validity. Policy makers have an interest in both of these issues. Nine demographic and preadmission factors were investigated to identify their ability to predict performance on the nurse-midwifery national certification examination. This retrospective analysis included 1,046 candidates who took any one of five criterion-referenced, modified essay forms of the examination between January 1988 and April 1994. Multiple regression analysis revealed that five factors explained 16.2% of the variance in certification examination performance. These factors included age (as age increased, scores decreased slightly), ethnicity (white and Hispanic candidates received higher scores compared with other groups), years of nursing practice prior to nurse-midwifery education (a slight positive influence for each additional year), highest educational degree obtained (those whose highest degree was the baccalaureate performed slightly better than candidates with no degree and candidates with graduate degrees), and academic level of the nurse-midwifery education program (certificate, master's, and doctoral level candidates all performed better than candidates from precertification programs; certificate candidates performed slightly better than master's candidates). However, even though these variables contributed to a statistically significant model, the actual degree of predicted difference in scores was of little practical significance. Variables that were not predictive of performance included marital status, U.S. versus foreign education either in nursing or in midwifery, and academic level of the registered nursing educational program [corrected]. PMID- 7869146 TI - Incorporating routine screening for history of childhood sexual abuse into well woman and maternity care. AB - Despite a rapid expansion in the understanding of the incidence and effects of childhood sexual abuse in the mental health disciplines, health care disciplines have only begun to look at the effect of an abuse history on women's health. Little is known from research about its influence on a woman's gynecology care or childbearing experience. The literature across disciplines advocates for routine screening for history of childhood sexual abuse. Asking about childhood sexual abuse will benefit women who have been abused and will help build a database from which to gain clinical knowledge about their care. This review presents clinical reasons to screen, discusses barriers and benefits, and emphasizes manageable ways to incorporate asking about childhood sexual abuse into practice. PMID- 7869147 TI - Effectiveness of postpartum education received by certified nurse-midwives' clients at a university hospital. AB - This pilot study's objective was to determine the effectiveness of postpartum education received by midwifery clients at the University of New Mexico Hospital. The authors of the study randomized 100 women following delivery to two groups. Group one, n = 55, received written postpartum instructions only. Group two, n = 45, received oral instructions by the certified nurse-midwife in addition to the written instructions. Both groups answered a written questionnaire after the teaching. Analyses were carried out on 100 posttest scores. Mean test scores for group one was 17.9 out of a possible score of 20. Mean score for group two was 18.3. No significant difference was detected between these two mean scores. A 95% confidence interval for the difference between mean scores was -1.9 to 1.1 (P > .05). Reliability of instrument was established via the Kuder-Richardson formula 21. This conservative estimate of internal consistency yielded r = .50. The authors found that oral instructions by the certified nurse-midwife did not significantly increase the knowledge of primiparas as evidenced by posttest results. However, results must be interpreted cautiously for three reasons: low reliability of the instrument, the small difference between groups, and the sample size. The need to determine how best to approach postpartum education is imperative in this era of early hospital discharge. A certified nurse-midwife's time may be better spent focusing on individual concerns rather than on a set teaching agenda. Alternative opportunities such as postpartum home visits need to be explored as a means of providing support and guidance to new mothers. PMID- 7869148 TI - Rethinking iron supplementation during pregnancy. AB - Iron supplementation is an intervention frequently initiated without adequate data collection to identify iron deficiency. The physiologic changes of normal pregnancy result in lowered hemoglobin and hematocrit levels and make these lab values difficult to interpret. Because excess iron intake by healthy women may have harmful sequelae, safe practice requires an individual assessment of iron status. PMID- 7869149 TI - Maternal age and labor complications in healthy primigravidas at term. AB - The objective of this study was to describe the association between maternal age and selected risk indicators (both recognized and potential) to determine whether any were predictive of labor complications in women having a first child. Low risk primigravidas (n = 1,792) were selected from a large national probability sample of births for 1988 (the National Maternal and Infant Health Survey). Recognized and potential risk indicators were described according to categories of maternal age and the occurrence of labor problems. Stratified analysis and logistic regression were used to assess the association of various risk factors with labor complications adjusted for maternal age. Only cesarean delivery varied significantly across maternal age groups, the rate being 11.6% for those < 20, 15.9% for those age 20-29, and 28.3% for those > or = 30. Cesarean delivery was associated with several characteristics of social advantage. Independent risk factors for cesarean delivery were maternal age (particularly > or = 30), epidural anesthesia, and receipt of adequate prenatal care. We conclude that older primigravidas have significantly more cesarean deliveries, and this is partially explained by characteristics of social advantage. To address the high cesarean rate, care providers need a better understanding of the relationship between social circumstances and cesarean delivery. PMID- 7869150 TI - Nurse-midwifery: old art--new science. PMID- 7869151 TI - Odd aberrations and double-pass measurements of retinal image quality. AB - We investigated the formation of the aerial image in the double-pass method to measure the optical quality of the human eye. We show theoretically and empirically that the double pass through the eye's optics forces the light distribution in the aerial image to be an even-symmetric function even if the single-pass point-spread function is asymmetric as a result of odd aberrations in the eye. The reason for this is that the double-pass imaging process is described by the autocorrelation rather than the autoconvolution of the single-pass point spread functions, as has been previously assumed. This implies that although the modulation transfer function can be computed from the double-pass aerial image, the phase transfer function cannot. We also show that the lateral chromatic aberration of the eye cannot be measured with the double-pass procedure because it is canceled by the second pass through the eye's optics. PMID- 7869152 TI - Suppression of flicker response with increasing test illuminance: roles of temporal waveform, modulation depth, and frequency. AB - This study examined the detectability of flicker for small foveal long-wavelength test stimuli centered within surrounding long-wavelength annular adaptation stimuli. Flicker threshold-versus-illuminance (tvi) curves were analyzed for four different test-stimulus waveforms--sine-wave, square-wave, and rapid-on sawtooth and rapid-off sawtooth flicker--at temporal frequencies ranging from 12 to 21 Hz and at temporal modulation depths ranging from approximately 50% to 100%. For all stimulus combinations that were examined involving temporal frequencies above 12 Hz, the resultant flicker tvi curves shared the following characteristic features: First, at operationally dim surround illuminances, there was always a single elevated threshold for detection of flicker. Second, some surround illuminance always could be found for which flicker threshold decreased abruptly, typically by approximately 1.5 log units within 0.1 log unit of surround illuminance increase. Third, when test illuminance was incremented above this lower flicker threshold, flicker always vanished; when test illuminance was incremented still further, flicker reappeared. Finally, at sufficiently bright surround illuminances flicker did not disappear with increasing test illuminance. Although these effects held for all waveforms, the abrupt decrease of flicker threshold occurred at brighter surround illuminances for sawtooth than for sine wave flicker, and at brighter surround illuminances for sine-wave than for square wave flicker, at least for fully modulated waveforms (of a given temporal frequency). Moreover, when modulation depth was adjusted so that any two different waveforms had the same first-harmonic contrast, the resultant flicker tvi curves became identical when plotted as first-harmonic amplitude versus surround illuminance. This identity held for any given temporal frequency, even though the flicker tvi curves for 12-Hz fully modulated sine-wave or square-wave flicker did not manifest flicker response suppression, whereas the flicker tvi curves for sawtooth flicker did. These and other results imply that the first harmonic contrast of the test stimulus fully determines the shape of the entire flicker tvi curve and that the dc component of the test stimulus helps to cause flicker response suppression. The results also demonstrate that first-harmonic equivalence is only a necessary, not a sufficient, condition for linearity. PMID- 7869153 TI - Binocular processes in vernier acuity. AB - We investigate the role of binocular mechanisms in vernier acuity, using dichoptic variants of spatial-frequency masking and flank-line interference paradigms. The finding that grating masks and flanking lines presented to one eye elevate (worsen) thresholds for detecting vernier offsets presented to the other eye suggests that neural mechanisms mediating vernier acuity receive binocular inputs, thus placing the loci of these mechanisms at postreceptoral sites. The observation that these threshold elevation effects are orientation dependent is consistent with a contribution to vernier acuity from oriented cortical filters. PMID- 7869154 TI - Apparent motion produced by temporally modulated brightness contrast and assimilation. AB - When regions containing a counterphasing sine-wave grating are presented side by side and in spatial and temporal quadrature phase, a transparent perception of motion results. This occurs even though none of the stimulus parts is moving. The two percepts of motion in these displays are in opposite directions, one analogous to brightness contrast, the other to brightness assimilation. If the regions are separated by a gap, the contrast and assimilation motions remain visible for separations up to 0.5 and 1 period, respectively. Both motions occur at temporal frequencies from 1 to 16 Hz. The perceived motion analogous to brightness assimilation is easily modeled with elongated receptive fields that integrate flux along the long axis, such as simple cells. The perceived motion analogous to brightness contrast can be accounted for by receptive fields that subtract the flux in one region from the flux in another region. Examples are center-surround subunits such as are found in the elaborated Reichart model [W. Reichardt, in Sensory Communication, W. A. Rosenblith, ed. (MIT Press, Cambridge, Mass., 1961), pp. 303-317; J. P. H. van Santen and G. Sperling, J. Opt. Soc. Am. A 2, 300-321 (1985)]. The dual perceived motion suggests that more than one kind of motion channel (distinguished by the two-dimensional receptive field of the front-end filter) is present in the human visual system. PMID- 7869155 TI - Mechanisms subserving temporal modulation sensitivity in silent-cone substitution. AB - Temporal contrast sensitivity data were collected with sine-wave-modulated lights for achromatic, chromatic, and silent-cone-substitution stimuli. Achromatic (556- and 642-nm lights in phase) and chromatic (556- and 642-nm lights in counterphase) modulation sensitivities were measured at a constant time-average retinal illuminance of 1256 trolands (Td) and chromaticity of 595 nm. These data were considered to represent isolated temporal responses of luminance and red green chromatic channels, respectively. Silent cone substitution was achieved with counterphase modulation of the 556- and the 642-nm lights and by suitable adjustment of the modulations or the radiances of the two lights. (1) The peak modulation depth of the 642-nm light was reduced to silence the long-wavelength sensitive (LWS) cone, and the peak modulation depth of the 556-nm light was reduced to silence the middle-wavelength-sensitive (MWS) cone. These protocols maintained the time-average retinal illuminance and chromaticity as for the control conditions. (2) The luminance of the 642-nm light was decreased to silence the LWS cone and was increased to silence the MWS cone. In this procedure the time-average retinal illuminance and chromaticity differ for the silenced-LWS cone (1047 Td and 589.5 nm) and the silenced-MWS-cone (4358 Td and 622 nm) conditions. The response modulation of the achromatic and the chromatic channels was calculated for the silent-substitution conditions. The chromatic channel is more sensitive at low frequencies, with a transition to greater achromatic channel sensitivity near 13 Hz for the silenced-LWS-cone condition and near 6 Hz for the silenced-MWS-cone condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869156 TI - Color and luminance spatial tuning estimated by noise masking in the absence of off-frequency looking. AB - We assessed the contribution of off-frequency looking for pattern detection and obtained bandwidths for chromatic and luminance mechanisms in conditions free from this effect. We used a simultaneous spatial masking technique with Gaussian enveloped sinusoidal test stimuli (0.5 cycle/deg) and filtered one-dimensional static-noise masks whose spectral power was uniformly distributed per octave. Stimuli were modulated in the chromatic (isoluminant red-green) or the luminance (yellow-black) domain. Color and luminance detection thresholds were compared for low-pass, high-pass, and notch- (band-stopped) filtered noise. We obtained the following results: (1) at high-noise spectral densities, masking by notched noise is greater than the summed masking of the high- and low-pass noise, indicating the presence of off-frequency looking for both color and luminance detection. There is no evidence for off-frequency looking at lower power densities. (2) Using notch-filtered noise, which avoids the problem of off-frequency looking, we found that color processing is subserved by bandpass channels with bandwidths similar to those revealed for luminance processing. (3) Both color and luminance mechanisms appear to have bandwidths proportional to their center frequency (constant in octaves). (4) The lower and upper sides of the color and luminance tuning functions were estimated individually by use of high-pass and low-pass noise of a low power density and are revealed to be asymmetric, with the lower side declining more steeply than the upper side. PMID- 7869157 TI - Illuminant changes under different surface collections: examining some principles of color appearance. AB - I report the results of a set of experiments designed to study whether the visual system's adjustments to illuminant changes vary with the surface collection in a scene. Simulations of flat matte surfaces rendered under diffuse illumination were presented on a CRT monitor. Under several surface collections subjects set asymmetric color matches between a standard surface and a test surface that were rendered under illuminants with different spectral power distributions. The three subjects' data span 28 different illuminant x surface collection conditions. Five different standard surfaces were used. Two results stand out. First, a change in surface collection did not induce a substantial change in the effect of illuminant changes on the subjects' settings. In this sense the results are consistent with the hypothesis that the visual system's adjustments to illuminant changes do not depend on the surface collection. Second, the illuminant-induced changes in the subjects' settings for a given surface collection were well approximated by a von Kries model, in which the change in the von Kries coefficients is a linear function of the illuminant change. In addition, I tested the hypothesis that the gain of the signal from each cone class is regulated by the photopigment absorptions originating entirely within that cone class. I found some clear deviations from this hypothesis, which indicates interactions among the cone classes. A first-order quantification of these interactions is provided. PMID- 7869158 TI - Bicondylar tibial plateau fractures treated with a hybrid ring external fixator: a preliminary study. AB - Twenty-three knees in 22 patients with Schatzker type VI tibial plateau fractures were treated with a hybrid ring external fixator using tensioned wires proximally and half-pins distally. All but two injuries were secondary to high-energy trauma. Six were open injuries, and eight patients had other major musculoskeletal trauma. Eight patients were treated with limited open reduction and internal fixation before application of the frame. The remainder received percutaneous cannulated screw fixation to stabilize the articular surface without opening the fracture site. Twenty-three fractures were followed to complete healing. Average time to healing was 4.4 months. Arc of motion averaged 107 degrees, and there were four flexion contractures of 5-15 degrees. Complications consisted of three deep wound infections, one deep venous thrombosis (DVT), one malunion, and one pin tract infection. The average knee score and patient function score were 84.7 and 80.5, respectively (Knee Society Clinical Rating System). There were 13 excellent, three good, one fair, and six poor results. The poor results were in patients who either developed deep wound infections or in those who sustained multiple musculoskeletal trauma compromising the patients' function score and ultimately the average score. This method provides good stabilization and allows early range of motion for complex tibial plateau fractures where extensive dissection and internal fixation are contraindicated due to traumatized soft tissue, osteopenia, and fracture comminution. PMID- 7869159 TI - Effects of retained diaphyseal plates on forearm bone density and grip strength. AB - Numerous complications have been attributed to elective plate removal following successful treatment of both bone diaphyseal forearm fractures, yet the effects of retained implants are not known. Fourteen patients were reviewed for residual forearm grip strength (FGS) and bone mineral density (BMD) following uneventful union. Patients were analyzed in two groups based upon time from fixation: group I, > 2 years but < or = 5 years, and group II, > 5 years. In group I, mean 2.6 years follow-up (n = 6), mean FGS ratios (patient values/age matched general population means) were 0.65 and 0.77, respectively, for plated and normal limbs (p = 0.08). The mean BMD ratios of plated/normal sides adjacent to the plate were 0.99 (ulna) and 1.02 (radius); these values were not significantly different from more proximal forearm BMD ratios (p = 0.92 ulna; p = 0.44, radius). In group II, mean 8.4 years (n = 8), mean FGS ratios were 0.97 and 1.09, respectively, for plated and normal limbs (p > 0.05). The BMD ratio was 1.04 adjacent to the plate; this was not significantly different from the ratios measured away from the plate (p > 0.4). We conclude that retained forearm plates can be well tolerated and that their routine removal is not indicated based on FGS or BMD. PMID- 7869160 TI - Biomechanical evaluation of methods of internal fixation of the distal humerus. AB - The best results following fractures of the distal humerus are provided by anatomic reduction and rigid internal fixation. Plates of two designs placed in five different fixation configurations were used to determine the construct that would maximize rigidity of fixation of the distal humerus. Using a cadaver distal humerus osteotomy, with and then without cortical contact, motion of the distal fragment was measured with respect to the proximal fragment in axial and torsional loading, anterior to posterior and posterior to anterior bending, and lateral to medial and medial to lateral bending. With cortical contact, two plates when placed medial and lateral or at 90 degrees to each other provided equivalent rigidity. However, with a cortical gap, the combination of a specially designed anatomic lateral buttress "J" plate and a medial reconstruction plate gave the greatest rigidity (ANOVA, p < 0.05). Two-plate constructs do not require placement at 90 degrees to obtain sufficient rigidity, but do require placement on separate bony pillars and different surfaces. PMID- 7869161 TI - Internal fixation of the unstable anterior pelvic ring: a biomechanical comparison of standard plating techniques and the retrograde medullary superior pubic ramus screw. AB - The purpose of this study was to evaluate pubic ramus fracture fixation. This biomechanical evaluation compared standard plating techniques with retrograde medullary screw fixation of a superior pubic ramus fracture in a pelvic fracture model. Six fresh-frozen, cadaveric pelvic specimens with a mean age of 79 years were harvested. These specimens were physiologically loaded according to the following modifications and instrumentations: (a) intact; (b) an APC-II unstable pelvic injury, specifically, unilateral superior and inferior rami osteotomies combined with ipsilateral anterior sacroiliac (SI) joint, sacrospinous, and sacrotuberous ligamentous disruptions, without fixation; (c) disrupted as in (b) but fixed anteriorly with a 10-hole 3.5-mm reconstruction plate contoured to the superior ramus and secured with four 3.5-mm cortical screws; (d) disrupted as in (b) but fixed anteriorly with a 10-hole 3.5-mm reconstruction plate contoured to the superior ramus and secured with six 3.5-mm cortical screws; (e) disrupted as in (b) but fixed anteriorly with a 4.5-mm retrograde medullary superior pubic ramus cortical screw 80 mm long (medial to the hip joint); and (f) disrupted as in (b) but fixed anteriorly with a 4.5-mm retrograde medullary superior pubic ramus cortical screw 130 mm long that was extraarticular and engaged the lateral iliac cortex cephalad to the ipsilateral hip joint. The posterior disruptions of the pelvic ring were not fixed. The APC-II injury created in this study resulted in significant (p < 0.05) motion at the disrupted rami and the injured SI joint, compared with the intact pelvic specimen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869162 TI - Box plate fixation of the symphysis pubis: biomechanical evaluation of a new technique. AB - The purpose of this study was to compare common techniques of pubic symphyseal fixation with a new method, the "box plate," for fractures of the pelvis where the bone is osteopenic. This symphyseal fixation construct consists of two, two hole, 4.5-mm narrow dynamic compression plates (DCP) oriented parallel to one another. One plate is recessed within the symphysis, and the other is located on the pubic tubercles. The plates are interlocked using two 6.5-mm fully threaded screws, forming a box-like construct. To determine the mechanical properties of this construct, five fresh, cadaveric pelvic specimens with a mean age of 75 years were harvested. The femora of each specimen were potted into containers and fixed to the base of a materials testing machine. The pelvis was constrained from rotating about the hip joints by anterior and posterior restraints. A vertical compressive load was applied through the lumbar spine. Force to a magnitude of 1,000 N was applied through three cycles. Gapping motions at the symphysis pubis (SP) and the sacroiliac (SI) joints, and flexion-extension of the sacrum with respect to the ilia were measured under the following conditions: (a) intact, (b) SP ligament, unilateral anterior SI ligaments, and ipsilateral sacrospinous and sacrotuberous ligaments disrupted (anteroposterior compression type II injury), and these injuries fixed using (c) a 4.5-mm narrow two-hole DC plate placed on the superior SP held by two cancellous bone screws, (d) the DC plate well as a single 7.0-mm cannulated cancellouoffliosacral lag screw across the injured SI joint, (e) the DC plate and a five-hole 3.5-mm reconstruction plate on the anterior SP, (f) a 3.5-mm, four-hole, DC plate on the superior SP using four fully threaded screws, and (g) the box plate symphyseal construct described above. All fixations reduced SP joint gapping compared to the disrupted joint. However, all but the box plate still allowed significantly greater motion than the intact SP joint. No fixation significantly reduced SI joint gapping or sacral flexion compared to the injured state. PMID- 7869163 TI - An experimental rat model allowing controlled delivery of substances to evaluate fracture healing. AB - We present a method to study the in vivo delivery of any substance in a rat femur fracture model that allows precise administration with control of both substance dosage and temporal application in a reproducible and predictable manner. This method is easy to perform, requires no expensive materials, and provides the benefit of internal stabilization of the femur fracture. In this model, all wounds are closed after surgery with no external ports or catheters, significantly reducing the infection rate and the risk of dislodgement due to animal intervention. This model allows the study of different substances given at different times in the same animal, providing the potential to improve our understanding of the interactions of various substances on normal fracture healing. PMID- 7869164 TI - Femur fractures with femoral or popliteal artery injuries in blunt trauma. AB - The treatment and results of 13 blunt femoral fractures with an arterial injury were reviewed. Two of the 13 patients (15%) sustained segmental (two levels) arterial injuries. Stabilization of the femur fractures were performed before arterial repair in 10 of the 13 femurs. The results were determined at an average of 4.5 years. For the eight open fractures, two patients had above-knee amputations, no limb regained > 90 degrees of knee motion, four patients required a brace or cane, and three patients have intermittent wound drainage. The five closed fractures all regained full function with full knee motion. Due to the 15% incidence of segmental arterial injury, "wide-field" arteriography is advised for the evaluation of this injury. Femoral stabilization may be performed before arterial repair if the procedure does not encroach on the viability of the limb. The functional results depend on the soft-tissue damage, as illustrated by the poor results seen in open fractures. PMID- 7869165 TI - The treatment of open tibial shaft fractures using an interlocked intramedullary nail without reaming. AB - Between January 1989 and September 1991, 117 consecutive open tibial shaft fractures were treated at our institution. Of these, 64 (55%) met the inclusion criteria and were prospectively treated according to protocol using unreamed interlocking intramedullary nails as definitive fixation. Wounds were classified according to the method of Gustilo et al., and included 10 type I, 16 type II, and 38 type III (17 type IIIA, 21 type IIIB) wounds. Contraindications to intramedullary nailing included (a) fractures involving the proximal or distal one fifth of the tibia, (b) patients with open physes, and (c) an associated vascular injury (type IIIC). Proximal locking was routinely performed, whereas distal locking was used as needed for axial and/or rotational stability. Soft tissue coverage was obtained after adequate debridement within 7 days: 26 of 64 fractures (41%) required a soft-tissue procedure (17 split-thickness skin grafts, eight free-tissue transfers, one rotational muscle flap). Patients were encouraged to bear full weight in a short leg cast or Sarmiento brace as soon as other injuries or pain permitted. Average follow-up time was 24.8 months (range 12-44) and was possible in 46 fractures (71.875%; nine of 10 type I, 12 of 16 type II, 10 of 17 type IIIA, and 15 of 21 type IIIB). Mean time to healing was as follows: type I, 4.8 months; type II, 4.7 months; type IIIA, 8.28 months; and type IIIB, 9.30 months. Twenty fractures exhibited a delay in healing (> 6 months). This included two of 12 type II (16%), six of 10 type IIIA (60%), and 12 of 15 type IIIB fractures (80%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869166 TI - Effects of imposed hindfoot constraint on ankle contact mechanics for displaced lateral malleolar fractures. AB - Contact stress distributions on the tibial plafond were mapped in a series of eight fresh-frozen cadaver specimens in which displaced lateral malleolar fractures were studied. These included gripping (a) by snugly lacing the foot in an athletic shoe, (b) by polymethylmethacrylate potting of the calcaneus alone, and (c) by potting of the calcaneus plus talus. Each of these three gripping conditions was tested both for rigid and for nearly frictionless transverse external constraint conditions. Across the series, the grip-dependent changes in contact stress distributions were found to be very minor compared with the wide interspecimen variability that was consistently present. Moreover, although contact stresses generally increased with progressive lateral fibular fragment offsets of up to 5 mm, such an effect was far more modest than that seen in previous cadaver work. The present laboratory cadaver findings suggest that the contact stress elevations occurring clinically for displaced lateral malleolar fractures are probably relatively mild and likely not directly responsible for late secondary degeneration. PMID- 7869167 TI - Ilizarov's technique in correction of ankle malunion. AB - A case is reported of ankle malunion corrected using Ilizarov's technique. The malunion, resulting in a varus ankle deformity (30 degrees), was a consequence of a posttraumatic epiphysiodesis of the distal growth plate of the tibia (McFarland's fracture). Ilizarov's procedure is described, and the radiological evolution of the regenerate is presented. Indications of corrective surgery in ankle malunion are discussed. The advantages of Ilizarov's technique (bloodless technique, cosmetic advantage, full weight-bearing capability, immediate talotibial joint rehabilitation) are illuminated. PMID- 7869168 TI - Irreducible Salter-Harris type II fracture of the distal tibial epiphysis. AB - An 11-year-old boy was admitted to the hospital after he fell to the ground from the roof, complaining of pain in his left ankle. Radiographs showed a Salter Harris type II fracture-separation of the distal tibial epiphysis together with a transverse bending fracture of the distal fibula. An attempt at closed reduction was unsuccessful. At open reduction, torn periosteum and the posterior tibial tendon were interposed between the tibial metaphysis and epiphysis. After the tendon was deflected to its normal position, fracture-separation of the distal tibial epiphysis was easily reduced. At the latest follow-up 4 years after surgery, radiographs showed no evidence of growth arrest or residual deformity. PMID- 7869169 TI - Severity scores in open fractures of the tibia. PMID- 7869170 TI - [The 95th Congress of the Japanese Society of Otolaryngology. Niigata, Japan. May 19-21, 1994. Abstracts]. PMID- 7869171 TI - Paroxysmal nocturnal hemoglobinuria: new discoveries about an old disease. PMID- 7869172 TI - Antineutrophil cytoplasmic autoantibodies in the immunodiagnosis of systemic necrotizing vasculitis. AB - If testing of ethanol-fixed neutrophils remains the most commonly used method to screen for ANCA. C-ANCA is highly sensitive and specific for Wegener's granulomatosis if strict criteria in defining this IF pattern are followed. P ANCA is not specific for MPO-ANCA, when used as a screening test. Because of the increasing recognition of atypical cytoplasmic staining patterns and the lack of specificity of nuclear staining of neutrophils for MPO-ANCA, confirmatory testing by ELISA is advisable in all cases of atypical neutrophil cytoplasmic staining and in all cases of neutrophil nuclear or perinuclear staining. PMID- 7869173 TI - Contemporary concepts for the clinical and laboratory evaluation of systemic lupus erythematosus and "lupus-like" syndromes. AB - Systemic lupus erythematosus (SLE) is a nonorgan-specific autoimmune disease which affects multiple organ systems and is multifactorial in etiology. SLE is the prototypic systemic rheumatic disease with immune dysregulation characterized by (1) polyclonal activation of B-cells and (2) production of a large spectrum of autoantibodies with a marked preference for nuclear and intracellular antigens. The clinical and laboratory manifestations and criteria for classification and diagnosis of systemic lupus erythematosus, lupus-like syndromes, and various subsets of systemic lupus erythematosus, are reviewed. The differential diagnosis of SLE and related diseases is described with correlation of specific intracellular autoantibodies. PMID- 7869174 TI - Current status of available standards for quality improvement of assays for detection of autoantibodies to nuclear and intracellular antigens. AB - Considerable progress has been made in the improvement of clinical assays for the detection of autoantibodies to nuclear and intracellular antigens with the use of available World Health Organization (WHO) and Arthritis Foundation/Centers for Disease Control (AF/CDC) standards. The ultimate goal of standardization is for various clinical laboratory test results to be interchangeable and for an exchange of data to be done with confidence. This report discusses the available standards. In addition, significant technical problems and variations in methodologies for the detection of autoantibodies to intracellular antigens noted during a 4-year study by a European Consensus Study Group are detailed. Currently, there is a need for a future generation of reference preparations and standards that will show specific antibody reactivity on sensitive enzymes and immunoblotting assays. Standardization efforts should be done to characterize specific nuclear and cellular antigen preparations that may be of natural or of recombinant technology origin. PMID- 7869175 TI - Laboratory diagnosis of human hepatitis viruses. AB - Conventional serologic methods of antigen or antibody detection are now widely applied for diagnosis of hepatitis viruses A, B, C, and D. Nucleic acid quantitation has become very useful for monitoring response to antiviral therapy in cases of hepatitis B and C. Special confirmatory testing of HCV serologies can be quite specific, but overall serologies for HCV lack sensitivity for early diagnosis. Thus HCV RNA detection may ultimately be the preferred method for HCV diagnosis and for screening blood donors. Unfortunately, HEV diagnosis may rest on the efforts of research laboratories for electron microscopy, Western blot, or nucleic acid detection. PMID- 7869176 TI - Anti-glycosphingolipid autoantibodies in rheumatologic disorders. AB - Antibodies directed against ganglioside GM1 or sulfatides are frequently associated with motor or sensorimotor neuropathies. To establish the prevalence of such anti-glycosphingolipid autoantibodies in autoimmune disorders and to determine whether they contribute to neurologic symptoms in those individuals, we measured these antibodies by enzyme-linked immunosorbent assay (ELISA) in serum samples from rheumatologic patients with and without peripheral neuropathies (PN). We tested 21 patients with systemic lupus erythematosus (9 with PN), 26 with Sjogren's syndrome (12 with PN), 34 with scleroderma (28 with PN), and 14 with rheumatoid arthritis (4 with PN). Samples from 32 normal individuals were also tested. Patients with systemic lupus erythematosus and rheumatoid arthritis had elevated concentrations of GM1 antibodies and scleroderma patients had lower levels of sulfatide antibodies compared to healthy individuals. The presence of ganglioside or sulfatide antibodies did not correlate with the development of peripheral neuropathy in these patients. These findings suggest that relatively low-titer glycosphingolipid antibodies may arise as part of a nonspecific polyclonal gammopathy in rheumatologic disorders but generally without clinical manifestation. PMID- 7869177 TI - Measurement of serum Lp(a) by COBAS MIRA using a latex immunoturbidimetric assay kit. AB - We had an opportunity to test a reagent kit for serum lipoprotein (a) [Lp(a)] assay, which was based on the latex immunoturbidimetric assay method, and applied it to COBAS MIRA (Roche). Reproducibility of the assay procedure was 0.92-4.0% CV of three samples which contained 12.58-60.4 mg/dl of Lp(a). Minimum detectable concentration was 1.5-2.0 mg/dl. It was confirmed that interference of co existing substances, i.e. hemoglobin, bilirubin, and intralipid, was negligible. No cross reactivity was seen with plasminogen. Correlation with a ELISA method was excellent. Frequency distribution of Lp(a) in healthy Japanese was similar to that found in white population. PMID- 7869178 TI - Comparison of techniques for minimizing interference of bilirubin on serum creatinine determined by the kinetic Jaffe reaction. AB - This study compared the effect of sodium dodecyl-sulfate, potassium ferricyanide, and preincubation technique to continuous-flow analysis and prior deproteinization to correct the negative interference of bilirubin on serum creatinine found by the kinetic Jaffe reaction. Bilirubin increased to 684 mumol/L did not interfere with serum creatinine measured by the methods incorporated with dialysis or deproteinization. Trichloroacetic acid was the best protein precipitant. The reagent incorporated with sodium dodecyl sulfate was more appropriate to minimize bilirubin interference than reagent containing potassium ferricyanide. An increase in potassium ferricyanide concentration resulted in false positive creatinine values. Incorporation of both SDS and potassium ferricyanide in the reagent did not help in minimizing the bilirubin interference over use of each chemical alone. The 10 minutes of preincubation of the sample with alkaline buffer incorporating with either SDS or potassium ferricyanide before starting the Jaffe reaction was the appropriate way to overcome unconjugated bilirubin interference at a level of 342.0 mumol/L. However, the technique did not work uniformly with icteric patient sera containing conjugated, unconjugated, and delta bilirubin. This is a challenging problem that remains to be solved by the clinical chemist. PMID- 7869179 TI - Magnetophoresis: I. Detection of magnetically labeled cells. AB - A new method for the detection of magnetically labeled cells in suspension using an optical microscope is presented. The movement of individual cells in a nonuniform magnetic field (magnetophoresis) can be studied and the direction and velocity of their movement can be determined. Cell-associated magnetic particles (e.g., attached magnetic immunomicrospheres) influence these parameters. We developed a magnetophoresis chamber for measuring the movement of single cells in a high-gradient magnetic field. Paramagnetic erythrocytes were used to monitor the level of magnetic force in the chamber. Bw6 antigen-positive REH cells were used as a biological model. Magnetic microspheres coupled with anti-Bw6 antibody were used as magnetic labels. The movement of magnetically labeled REH cells was investigated versus the intensity of magnetic field. The magnetization of microspheres was experimentally determined by the Faraday balance method. Experimental and theoretical results substantiate the feasibility of detecting a single cell associated with a single magnetic microsphere. Thus, magnetophoresis provides a sensitive biometrical system for magnetically labeled entities. PMID- 7869180 TI - Isolation of porcine pancreatic islets: low trypsin activity during the isolation procedure guarantees reproducible high islet yields. AB - During the past few years, interest in xenotransplantation of porcine islets of Langerhans for the future therapy of type I diabetes has increased markedly. Therefore, we established a semiautomated digestion method for isolating islets from the porcine pancreas. However, although the isolation technique was standardized and collagenase of controlled quality was used, we were unable to attain high islet yields with a satisfactory degree of reproducibility. One hypothesis was that varying degrees of interference by donor pancreatic enzymes were responsible for this failure. The aim of this study was to examine the kinetics of four types of enzymatic activity during the isolation procedure, as well as their effects on islet yield: collagenase, trypsin, neutral protease, and clostripain. Our results indicate that while exogenous collagenase activity decreases slightly during the isolation procedure, the activity of the pancreas enzymes neutral protease and trypsin increases. In some cases, trypsin activity increases very strongly. A strong increase in trypsin activity correlates with poor islet yield, whereas low trypsin activity always correlates with high islet yield. Addition of the protease inhibitor Pefabloc to the isolation medium results in low trypsin activity and reproducible high islet yields. PMID- 7869181 TI - Analysis of Epstein-Barr virus in Hodgkin's disease: experience of a single university hospital in Korea. AB - Hodgkin's disease is known to be associated with Epstein-Barr virus (EBV) infection in Western countries, and viral nucleic acids and proteins have been identified within Reed-Sternberg (RS) cells, which are the histopathologic hallmark of the disease process. Twenty-five cases of Hodgkin's disease from a single university hospital in Korea were studied for evidence of EBV by in situ hybridization for EBV DNA and RNA and immunohistochemistry for an EBV latent protein. EBV nucleic acids were studied by a rapid (60 minutes) in situ hybridization procedure, which utilized biotinylated DNA probes specific for the following nucleic acid sequences: (1) EBV EBER1 RNA (an abundant RNA sequence expressed during latent EBV infection), (2) EBV NotI repeats (a tandemly repeated DNA sequence, which has been established to identify amplified EBV genome in lytic EBV infection), and (3) BAM HI W (a DNA sequence reiterated 11 times within the viral genome). In addition, immunohistochemistry for EBV latent membrane protein, a protein that is capable of inducing cellular transformation in cell culture, was also performed. EBV was identified within the neoplastic RS cells by at least one method in 19/25 cases (76%). The mixed cellularity subtype was the most common subtype associated with EBV infection (11/13-85%). In situ hybridization for EBV EBER1 RNA was the most sensitive method for EBV detection and was present in 17/25 cases. A significant proportion of Korean Hodgkin's disease cases is associated with EBV infection. PMID- 7869182 TI - Rapid fluorometric assay for mitochondrial proton adenosine triphosphatase activity for assessment of viability of liver graft tissue. AB - We developed an improved determination method of mitochondrial proton adenosine triphosphatase (ATPase) activity in the liver. The activity was measured fluorometrically with a 3,3'-dipropylthiodicarbocyanine iodide (diS-C3(5)), which is excited at 625 nm and emits fluorescence at 670 nm. This dye transmits the electric potential across the inner mitochondrial membrane. The fluorescence intensity of diS-C3(5) with mitochondria (100 microliters, 4-16 mg/ml protein) in a 2 ml potassium buffer (pH 7.4) was regarded as a standard electric potential. After confirming the activity of the mitochondrial electron transport chain by succinic acid (9 mumol), we inhibited the chain by antimycin A (1.25 micrograms). Fluorescence intensity decreased by adenosine 5'-triphosphate (ATP) (2 mumol) and oligomycin (25 micrograms) inhibited this depression. The value of mitochondrial proton ATPase activity was calculated as a percentage of the fluorescence intensity change by ATP per the standard electric potential. The activity of mitochondrial proton ATPase in the normal fresh rat livers was 50.3 +/- 2.2%. Good correlation (r2 = 0.807) between two methods for mitochondrial proton ATPase activity, our newly developed method and a conventional colorimetric method, was obtained in the rat livers with various conditions. This method has advantages that the proton ATPase activity can be measured in intact mitochondria, and all procedures can be completed within 40 min. It is suitable for the determination of mitochondrial viability of liver graft in the hepatic resections and transplantations. PMID- 7869183 TI - Chemiluminescent immunoassays: discrimination between the reactivities of natural and human patient antibodies with antigens from eukaryotic pathogens, Trypanosoma cruzi and Paracoccidioides brasiliensis. AB - Quantitative chemiluminescent enzyme-linked immunosorbent assay (ELISA) and dot blotting procedures were developed to evaluate the reactivity of human antibodies with crude antigens and purified molecules of parasites and fungi, mainly Trypanosoma cruzi and Paracoccidioides brasiliensis. Reproducible, highly sensitive, and strictly dose-responding results were obtained, with the specificity depending on the kind of antigen used. Mixed antigens (epimastigote membrane and HIV-1 heptapeptide) applied in dots could be independently recognized by specific sera. Purified antigens (T. cruzi F2/3 and P. brasiliensis gp43) at very small concentrations gave specific reactions with patients' sera diluted > or = 1:1,000 and were very poorly reactive or unreactive with natural antibodies using the chemiluminescent immunoassays. P. brasiliensis crude antigen Fava Netto polysaccharide antigen (FNPA) contained peptide epitopes recognized by natural antibodies and carbohydrate epitopes reactive with sera from histoplasmosis patients. It is very important that sensitive chemiluminescence immunoassays be used with purified antigenic molecules to ensure specificity for the diagnosis and follow-up of parasitic and fungal infections. PMID- 7869184 TI - Soluble MHC class I molecules in human body fluids. AB - Apart from their well-known function of antigen presentation in the form of peptides, major histocompatibility antigens (MHC) have been found to be unique markers of individual body odors in murine experimental models. In the current study we examined the nature and expression of soluble human MHC class I molecules in body fluids. Biochemical analysis of affinity purified serum class I molecules revealed a variety of molecules within the molecular weight region of 45 to 21 kD. SDS-Western blotting of HLA derived from hepatocytes and spleen cells suggested that much of the small molecular mass fraction of sHLA (< 45 kD) found in serum is derived from the liver. sHLA were detected and quantitated in serum, plasma, urine, cerebrospinal fluid, and sweat. No sHLA were detectable in cerebrospinal fluid (n = 20). In addition, sHLA was measured in serum of women during the menstrual cycle. A significant increase in sHLA was observed during the first half of the cycle, suggesting that sexual hormones may increase sHLA concentration. The observed increase was most prominent in women that were HLA A24. PMID- 7869185 TI - Enzymatic fluorometric assay for tissue cAMP. AB - cAMP is commonly measured using either immunoassay or high-performance liquid chromatography. The current methods are sensitive but may lack versatility and be expensive; also, radioactivity is potentially harmful to the operator and environment. Given these concerns, we developed a highly sensitive enzymatic fluorometric assay for cAMP. The method consists of five steps: (1) destruction of interfering compounds with apyrase, 5' nucleotidase, adenosine deaminase, and alkaline phosphatase; (2) conversion of cAMP to AMP; (3) conversion of AMP to ATP; (4) amplification of ATP by ATP-ADP cycling; and (5) fluorometric measurement of resultant NADPH. cAMP was measured in male Sprague Dawley rats anesthetized with pentobarbital. Stimulated rats (n = 4) received isoproterenol (16 micrograms/kg, s.q.) and aminophylline (20 mg/kg, s.q.), whereas controls (n = 4) received no additional drug. With the enzymatic fluorometric assay, cAMP content in heart, liver, and kidney (pmol/mg wet wt, mean +/- SEM) was 0.34 +/- 0.03, 0.33 +/- 0.03, and 0.92 +/- 0.11 in the control group and 0.77 +/- 0.10, 0.66 +/- 0.04, and 1.53 +/- 0.12 in the stimulated group, respectively. The total assay duration including sample reading procedure varied at 4.5-9.5 hr, depending on its sensitivity. cAMP from the same samples was measured using a commercially available enzyme immunoassay kit and was found to be very similar to the enzymatic fluorometric assay. We conclude that this new assay is sensitive, safe, versatile, and inexpensive and can be used to measure cAMP in multiple types of tissue, including biopsy samples weighing < 200 micrograms. PMID- 7869186 TI - Cytokine production in whole blood cell cultures of patients with Crohn's disease and ulcerative colitis. AB - Levels of the cytokines interleukin-1-alpha, -1-beta, and -2 (IL-1-alpha, IL-1 beta, IL-2), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN gamma) were measured in the mitogen-stimulated whole blood cell cultures from 96 patients with Crohn's disease (48 untreated, 12 treated with sulfasalazine, 36 treated with corticosteroids), 74 patients with ulcerative colitis (21 untreated, 25 treated with sulfasalazine, 28 steroid treated), and 360 healthy controls. The cytokines were measured 4 days after induction by a sensitive immunoenzyme assay. In the blood cell cultures of the untreated and sulfasalazine treated patients with Crohn's disease and ulcerative colitis higher levels of TNF-alpha, IL-1 alpha and IL-1-beta were found whereas IL-2 production was decreased and IFN gamma-production was not significantly different as compared to the controls. Leukocytes of the corticosteroid-treated patients with both diagnoses showed a lower production of all measured cytokines compared to the untreated patients. The same results were obtained, when the somewhat different counts of mononuclear cells in the peripheral blood of the patients and controls were taken into account. The elevated production of proinflammatory cytokines in the blood cell cultures suggests a systemic immune activation in patients with inflammatory bowel disease. PMID- 7869187 TI - Solid-phase polymerase chain reaction. AB - The polymerase chain reaction (PCR) has facilitated the diagnosis of infectious diseases and genetic disorders, because of its ability to amplify minute amounts of nucleic acids. To distinguish genes of interest from nonspecifically amplified DNA, PCR products commonly are fractionated by electrophoresis, transferred to membranes, and then probed with a labeled internal sequence-specific oligonucleotide. Alternatively, the PCR products have been labeled directly, and hybridized to immobilized oligonucleotide probes. These methods require the tedious physical transfer of the PCR products. In order to amplify and immobilize genes simultaneously, we have developed a simple solid-phase PCR method. The technique enabled us to detect the HIV envelope gene readily without any transfer of amplified DNA. PMID- 7869188 TI - HLA antigens and resistance to HIV. AB - The role of histocompatibility antigens in HIV infection has been investigated by several approaches. Thus the haplotype A1B8DR3 that is usually linked to autoimmune disorders seems to be associated with accelerated progression to AIDS. Cross-reactivity between MHC antigens and HIV-1 proteins is evident from alloimmunization experiments in mice and xenoimmunization of monkeys with human cells. Furthermore, recent reports suggest that some individuals with uncommon HLA antigens may be resistant to HIV infection. In addition to expressing cross reacting antigens with HLA, HIV also exhibits substantial amounts of host beta-2 microglobulin and HLA-DR attached to its surface. Taken together, these data are stimulating new hypotheses relevant for AIDS pathogenesis. Based on alloimmunization, novel approaches have also been proposed in attempts to promote an effective immune response to HIV. PMID- 7869189 TI - Cardiovascular, renal, and endocrine actions of dopamine in neonates and children. PMID- 7869191 TI - Relation of activity levels to body fat in infants 6 to 12 months of age. AB - We examined longitudinally the relation between body fatness and physical activity, adjusting for energy intake, in 31 healthy white infants. Measures of physical activity, dietary intake, and body composition were obtained at 6, 9, and 12 months of age. The percentage of body fat was inversely related to activity level, an association that became stronger with increasing age and remained significant after adjustment for dietary energy intake. The percentage of body fat was not related to energy consumed per lean body mass regardless of high or low activity level, nor was energy consumed related to physical activity. We conclude that the percentage of body fat in infants may be related more to their activity levels than to their energy intake. PMID- 7869190 TI - Definition and application of the discretionary screening indicators according to the National Cholesterol Education Program for Children and Adolescents. AB - OBJECTIVES: (1) To propose definitions for the discretionary screening indicators described by the National Cholesterol Education Program for Children and Adolescents (NCEP-Peds); (2) to examine the relative prevalence of major screening indicators (family history of premature heart disease and parental plasma cholesterol concentration > or = 6.21 mmol/L (240 mg/dl)) and discretionary screening indicators (excessive consumption of fat or cholesterol or both, smoking, diabetes, hypertension, and steroid use) in a family population; and (3) to evaluate the relative value of the major and the discretionary indicators in detecting high serum levels of low-density lipoprotein-cholesterol (LDL-C) (> or = 3.36 mmol/L (> or = 130 mg/dl)). DESIGN: Control cohort from a case-control study. SETTING: Lipid research clinic. PARTICIPANTS: White children and adolescents < 20 years of age from 232 nuclear families who participated in the Cincinnati Myocardial Infarction Hormone Study. MAIN OUTCOME MEASURES: (1) Number of children who have major and discretionary screening indicators; (2) sensitivity and specificity of the major and the discretionary screening indicators in identifying children with LDL-C concentrations > 3.36 mmol/L (130 mg/dl) (high LDL-C). RESULTS: With cutoff points of the 90th percentile for blood pressure, the 85th percentile for obesity, and the 80th percentile for dietary fat and cholesterol, and self-report for diabetes, smoking, and corticosteroid use, 54% of the 232 children in the cohort had one or more discretionary indicators. Additionally, applying the major screening indicators raised the percentage of children identified to 74%. Twenty eight percent had both major and discretionary indicators. Having a discretionary screening indicator did not increase the probability of having a major indicator. Applying both discretionary and major screening indicators to the cohort identified 96% of the children who had a high concentration of LDL-C; 30% of the children with high LDL-C levels were discovered solely by the discretionary indicators. Similar sensitivity and specificity were noted between the major and the discretionary indicators. Children with high LDL-C concentrations were more likely to have multiple screening indicators. CONCLUSION: Discretionary and major screening indicators suggested by the National Cholesterol Education Program for Children and Adolescents identify different subsets of children at risk of having premature cardiovascular disease. Both major and discretionary indicators contribute to the identification of children with high LDL-C concentrations. PMID- 7869192 TI - A cross-sectional study of catheter-related thrombosis in children receiving total parenteral nutrition at home. AB - We performed a cross-sectional evaluation of deep vein thrombosis (DVT) related to the use of central venous lines (CVLs) in all pediatric patients receiving home total parenteral nutrition at our institution (N = 12). All children (5 months to 17 years of age) were examined with bilateral upper limb venography. All CVLs were flushed daily with heparin (200 units). At the time of evaluation, 49 CVLs had been placed in the 12 children. Of the 39 CVLs removed, 27 (66%) were blocked; venograms had not been previously obtained except of one child. Eight children had clinical evidence of superficial collateral circulation in the upper portion of the chest and the upper extremities; five had intermittent symptoms of superior vena cava obstruction. On venography, 8 of the 12 children had extensive evidence of DVT; two were unilateral and six bilateral. Five children were treated with warfarin (0.12 to 0.28 mg/kg per day) to achieve an international normalized ratio of 1.4 to 1.8. Neither bleeding nor further CVL-related DVT has occurred. We conclude that the risk of CVL-related DVT in children requiring home total parenteral nutrition is high, and that venography should be performed early in the event of CVL blockage. A multicenter, controlled trial assessing optimal warfarin therapy in this patient population is indicated. PMID- 7869193 TI - Precocious puberty in children with neurofibromatosis type 1. AB - We undertook a comprehensive study of children with neurofibromatosis type 1 (NF 1) cared for in a large multidisciplinary clinic to determine the prevalence of precocious puberty and its relationship to optic pathway tumors (OPTs). Precocious puberty was diagnosed in 7 of 219 children with NF-1 (5 boys and 2 girls) examined between Jan. 1, 1985, and April 20, 1993. All seven children had OPTs involving the optic chiasm; they represented 39% of children with NF-1 and chiasmal tumors (95% confidence interval, 17% to 64%). Eleven prepubertal children (aged 2 to 10 years) with NF-1 and OPTs, and age- and sex-matched NF-1 control subjects without OPTs, underwent luteinizing hormone-releasing hormone (LH-RH) stimulation tests. Two boys with OPTs had pubertal luteinizing hormone (LH) responses, and testosterone levels > 10 ng/dl. Basal LH levels were also elevated in these two boys when tested with a very sensitive immunochemiluminometric assay. None of the children without an OPT had either a pubertal response to LH-RH or an elevated basal LH level. We conclude that precocious puberty in children with NF-1 is found exclusively in those who have OPTs involving the optic chiasm; it is a common complication in those children. With the use of a highly sensitive LH assay, biochemical evidence of hypothalamic pituitary-gonadal axis activation may be demonstrated, even without provocative testing. PMID- 7869194 TI - Immunologic characterization of children vertically infected with human immunodeficiency virus, with slow or rapid disease progression. AB - Cytokine production of unstimulated and mitogen-stimulated peripheral blood mononuclear cells of 31 children vertically infected with human immunodeficiency virus type 1 (HIV) and with different patterns of disease progression was evaluated to establish possible correlations between the immunologic and the clinical findings. Production of interferon gamma and interleukin-2 (type 1 cytokines), and of interleukin-4 and interleukin-10 (type 2 cytokines), was analyzed in seven symptom-free patients (Centers for Disease Control and Prevention class P-1B), 10 patients with mild symptoms (class P-2A), and 14 patients with severe symptoms (class P-2B-F). Cytokine production was compared with that of 10 age- and sex-matched control subjects who were seronegative for HIV. The HIV-infected patients produced significantly fewer type 1 cytokines and significantly more type 2 cytokines than the uninfected control subjects. No differences in the production of interferon gamma and interleukin-2 were detected among the different clinical categories of HIV-infected patients. In contrast, interleukin-4 production was augmented in the patients with class P-2A (p < 0.05) and class P-2B-F HIV infection (p < 0.03), in comparison with the children with class P-1B infection. The increase in interleukin-4 production was paralleled by an increase in the number of children with hyperimmunoglobulinemia E in each of the clinical groups (0% in class P-1B; 40% in class P-2A; and 71% in class P-2 B F infection). Similarly, interleukin-10 production was increased both in patients with class P-2A and in those with class P-2B-F infection, in comparison with the children with class P-1B disease (p < 0.006 and < 0.04, respectively). These data indicate (1) that vertically acquired HIV infection results in decreased production of type 1 cytokines and in increased production of type 2 cytokines, and (2) that an increased production of type 2 cytokines correlates with hyperimmunoglobulinemia E and is present in, and may be characteristic of, the symptomatic phases of childhood HIV infection. PMID- 7869195 TI - Cognitive assessment of school-age children infected with maternally transmitted human immunodeficiency virus type 1. AB - Thirty-three children vertically infected with human immunodeficiency virus type 1 (HIV-1), who were born before 1985, were followed in a single center, and had reached the age of 6 years, were studied and tested for school achievement. Of these 33 children, 24 were also tested for cognitive abilities, fine motor and language skills, and emotional adaptation. Of the 33 patients, 22 (67%) had normal school achievement at a mean age of 9.5 +/- 1.6 years. The mean IQ was 95 +/- 11, but 54% of the patients (13/24) had abnormal results on visual-spatial and time orientation tests, 44% had speech and/or language delay or articulation disorders, and 29% of the children and 42% of the parents had psychoaffective disturbances of intermediate or high severity. Normal school performance was positively correlated with results of the different cognitive tests and to a lesser extent with the absence of psychoaffective symptoms, but was independent of the mode of maternal infection or the parents' educational level. Children with normal school achievement had a higher percentage of circulating CD4+ lymphocytes during the course of infection. We conclude that children whose HIV-1 infection is maternally acquired have better cognitive abilities and school achievement than was initially thought, and that the percentage of circulating CD4+ lymphocytes during the first years of life appears to be predictive of future school adaptation or cognitive abilities. PMID- 7869197 TI - Adolescent medicine 1995. PMID- 7869196 TI - Long-term effects of L-thyroxine therapy for congenital hypothyroidism. AB - OBJECTIVE: To study the effects of initial and concurrent dose levels of L thyroxine on ability and behavior in children with congenital hypothyroidism. METHODS: An existing database, involving a large cohort of children with congenital hypothyroidism detected by neonatal screening, was analyzed retrospectively. There were 94 children: 89 were assessed at age 7 years for intelligence and selective cognitive abilities, and 87 at age 8 years for behavior, achievement, and selective abilities. RESULTS: Subjects were stratified by median split into low and high starting dose groups. The high-dose group performed better on indexes of intelligence, verbal ability, and memory but had more behavior problems reflecting increased anxiety, social withdrawal, and poorer concentration. The dose of L-thyroxine at age 8 years was negatively correlated with memory task performance. CONCLUSION: A higher starting dose of L thyroxine is beneficial for subsequent intellectual outcome in children with congenital hypothyroidism but may be associated with internalizing behavior problems. PMID- 7869198 TI - Brain metabolite changes on in vivo proton magnetic resonance spectroscopy in children with congenital hypothyroidism. AB - Localized in vivo proton magnetic resonance spectroscopy and imaging were performed in five children with untreated congenital hypothyroidism to look for biochemical markers of abnormal myelin and neuronal development. The patients had high levels of choline-containing compounds, which returned to normal with euthyroidism. These metabolic alterations may reflect blocks in myelin maturation that are reversible by thyroid hormone replacement throughout childhood. PMID- 7869199 TI - Lead poisoning: low rates of screening and high prevalence among children seen in inner-city emergency departments. AB - Of 254 children who were 1 to 6 years of age and were tested at two major inner city emergency departments, 65% had no record of previous lead screening in the previous 30 months, and 71% (97/137) and 50% (58/117), respectively, had blood lead levels > or = 0.48 mumol/L (10 micrograms/dl). The emergency department may be an appropriate resource for lead screening of selected inner-city children. PMID- 7869200 TI - Resolution of breath-holding spells with treatment of concomitant anemia. AB - We describe two children who had breath-holding spells that were accelerating in frequency and severity and in one case had recrudesced. Both patients had signs, symptoms, and laboratory findings of severe anemia. With correction of anemia the breath-holding spells promptly and completely resolved in each case. We conclude that in some patients anemia may be a factor contributing to breath-holding spells and that correction of concomitant anemia may produce amelioration or remission of the spells. PMID- 7869201 TI - Overinterpretation of gastroduodenal motility studies: two cases involving Munchausen syndrome by proxy. AB - Two children were thought to have an atypical gastroduodenal motility disorder because of the history and clinical course; both had received parenteral alimentation because of claims of inability to tolerate enteral feedings, and both continued to have unusual medical problems during parenteral alimentation. Both children had motility studies that were interpreted by a pediatric gastroenterologist to be "abnormal" and "diagnostic" of a motility disorder, but each was eventually shown to have a behavioral abnormality related to Munchausen syndrome by proxy. PMID- 7869202 TI - A missense mutation in a patient with guanosine triphosphate cyclohydrolase I deficiency missed in the newborn screening program. AB - A patient with guanosine triphosphate cyclohydrolase I deficiency passed the newborn phenylketonuria screening program. The characteristic clinical phenotype developed in a 5-month-old patient; elevated plasma phenylalanine, undetectable urinary pterins, and absence of the enzyme activity in a liver biopsy were present. A point mutation that results in an amino acid substitution from methionine to isoleucine at position 211 was proposed to be the cause for this new phenotypic expression of guanosine triphosphate cyclohydrolase I deficiency. PMID- 7869203 TI - Improved oxygenation during synchronized intermittent mandatory ventilation in neonates with respiratory distress syndrome: a randomized, crossover study. AB - In a randomized, crossover study, we compared arterial partial pressure of oxygen and of carbon dioxide between consecutive periods of conventional and synchronized intermittent mandatory ventilation (SIMV). We studied spontaneously breathing infants with an endotracheal tube in place. The infants were < 12 hours of age, had a diagnosis of respiratory distress syndrome, and had an arterial/alveolar oxygen ratio of < 0.25. The infants had a mean birth weight of 1077 gm and gestational age of 28 weeks. The mean rate of asynchrony on intermittent mandatory ventilation (IMV) was 52% (range, 36% to 76%), and on SIMV was < 1%. Infants were randomly assigned to IMV or SIMV as their initial ventilator mode and underwent ventilation for four 15-minute periods, and crossed over to the alternate mode after each period. Ventilator settings and the fraction of inspired oxygen were not changed between modes. At the end of each period, arterial blood gas measurements were obtained; 26 paired comparisons were made between modes. The mean arterial partial pressure of oxygen was significantly higher during SIMV than during IMV (mean, 61.5 vs 53.3 mmHg; p < 0.01). The mean arterial partial pressure of carbon dioxide was slightly lower during SIMV than during IMV (mean, 42.7 vs 41.3 mm Hg; p < 0.05). The improvement in oxygenation demonstrated with SIMV may allow a reduction in ventilator pressure or oxygen exposure in this group of infants, who are at risk of having complications of ventilation. PMID- 7869204 TI - Partial liquid ventilation in premature lambs with respiratory distress syndrome: efficacy and compatibility with exogenous surfactant. AB - OBJECTIVE: To determine the efficacy of partial liquid ventilation (PLV) by means of a medical-grade perfluorochemical liquid, perflubron (LiquiVent), in premature lambs with respiratory distress syndrome (RDS). Further, to determine the compatibility of perflubron with exogenous surfactant both in vitro and in vivo during PLV. DESIGN: Prospective, randomized, controlled study, with in vitro open comparison. SUBJECTS: Twenty-two premature lambs with RDS. INTERVENTIONS: In vitro assays were conducted on three exogenous surfactants before and after combination with perflubron. We studied four groups of lambs, which received one of the following treatment strategies: conventional mechanical ventilation (CMV); surfactant (Exosurf) plus CMV; PLV; or surfactant plus PLV. MEASUREMENTS AND MAIN RESULTS: In vitro surface tension, measured for three exogenous surfactants, was unchanged in each animal after exposure to perflubron. Lung mechanics and arterial blood gases were serially measured. All animals treated with PLV survived the 5 hours of experiment without complication; several animals treated with CMV died. During CMV, all animals had marked hypoxemia and hypercapnia. During PLV, arterial oxygen tension increased sixfold to sevenfold within minutes of initiation, and this increase was sustained; arterial carbon dioxide tension decreased to within the normal range. Compliance increased fourfold to fivefold during PLV compared with CMV. Tidal volumes were increased during PLV, with lower mean airway pressure. Resistance was similar for both CMV and PLV; there was no difference with surfactant treatment. CONCLUSIONS: We conclude that PLV with perflubron improves lung mechanics and gas exchange in premature lambs with RDS, that PLV is compatible with exogenous surfactant therapy, and that, as a treatment for RDS in this model, PLV is superior to the surfactant studied. PMID- 7869205 TI - Efficacy and cost analysis of treating very low birth weight infants with erythropoietin during their first two weeks of life: a randomized, placebo controlled trial. AB - OBJECTIVE: We hypothesized that using a higher dose of erythropoietin (Epo) and starting treatment on the first day of life would reduce the transfusion requirements of ventilator-dependent and non-ventilator-dependent very low birth weight (VLBW) infants. Moreover, we hypothesized that this treatment would be cost-effective. METHODS: We randomly assigned 20 ill newborn VLBW infants to receive either Epo (200 units/kg per day) or placebo during their first 2 weeks of life. The caregivers were unaware of the treatment assignments, and erythrocyte transfusions were administered according to hematocrit and signs of anemia. RESULTS: On day 1, reticulocyte counts and hematocrits were similar in the two groups. During the subsequent 2 weeks, reticulocyte counts of the placebo recipients fell significantly below those of the Epo recipients, but hematocrits in the two groups did not differ. More transfusions were received by the placebo recipients (mean = 1.4 per patient) than by the Epo recipients (mean = 0.2 per patient; p < 0.01). No adverse effects of Epo were noted, and the costs in the placebo group exceeded those in the Epo group. CONCLUSIONS: We conclude that administration of Epo to VLBW infants during the first 2 weeks of life results in fewer transfusions and is cost-effective. PMID- 7869206 TI - Neonatal mortality rate: is further improvement possible? AB - OBJECTIVE: To determine whether improvement in neonatal and infant mortality rates is possible or likely. SETTING: Regional neonatal intensive care unit. METHODS: Experience during a decade (1982-1991) was evaluated. We determined postnatal age at death and birth weight-specific and gestational age-specific mortality rates. Neonatal deaths (deaths before discharge) were categorized as "possibly preventable" or "probably unpreventable." RESULTS: Deaths occurring after 28 days ("postponed" deaths) contributed 9% of the total for the decade, and 5% for those with extremely low birth weight (ELBW; < 1000 gm) during the last 6 years; 47% of all deaths and 65% of deaths of ELBW infants occurred within 24 hours of birth. Congenital malformations accounted for 7%, 54%, and 66% of deaths when birth weight was 500 to 1499 gm, 1500 to 2499 gm, and > or = 2500 gm, respectively. In infants with birth weight > or = 1000 gm, probably unpreventable deaths (predominantly from congenital malformations, but also including hydrops and inborn errors of metabolism) accounted for 61% of deaths. Of deaths of ELBW infants, extreme prematurity (500 to 750 gm) accounted for 58%; major malformations and pulmonary hypoplasia contributed an additional 9%. CONCLUSION: During the decade, the gestational age at which there was a 50% survival rate fell from 26 weeks to 24 weeks and a marked increase in the survival rate occurred at birth weights < 1500 gm (VLBW) after the introduction of exogenous surfactant therapy. The number of possibly preventable deaths is now very small. For any substantial impact on mortality rates, it will be necessary to lower VLBW and ELBW rates. PMID- 7869207 TI - Twenty-month outcome in ventilator-dependent, very low birth weight infants born during the early years of dexamethasone therapy. AB - We sought to examine the effect of the introduction of dexamethasone therapy on health, growth, and neurodevelopmental outcome in very low birth weight (VLBW) infants at 20 months of age. We compared outcomes in all 86 VLBW infants (mean birth weight 871 gm, mean gestational age 26.4 weeks) who were ventilator dependent on day 21 of life during the 2 years preceding October 1988 (period 1), when dexamethasone therapy became accepted clinical practice in our unit, with outcomes in all 124 infants (mean birth weight 891 gm, mean gestational age 26.9 weeks) with similar ventilator status during the subsequent 2 years (period 2). In addition, we compared outcomes in infants who received dexamethasone during period 2 with those in a concurrent cohort of less ill infants who were not given dexamethasone. There were no significant differences between periods 1 and 2 in mortality rates after 21 days (17% vs 21%), need for home oxygen (23% vs 25%), oxygen dependence at 20 months of corrected age (11% vs 10%), rate of neurosensory impairment (24% vs 25%), and mean Bayley Mental scores (81.5 vs 77.2) or Psychomotor Development Index (81.6 vs 71.1). Infants who received dexamethasone during period 2 had significantly more severe lung disease and poorer respiratory, growth, and developmental outcomes. We conclude that VLBW infants with ventilator-dependent chronic lung disease have very poor outcomes, even when treated with dexamethasone. More information is needed from prospective, randomized trials before dexamethasone can be accepted as routine therapy for chronic lung disease. PMID- 7869208 TI - Postnatal attainment of intrauterine macromineral accretion rates in low birth weight infants fed fortified human milk. AB - HYPOTHESIS: Provision of more bioavailable mineral sources as human milk supplements enables very low birth weight (VLBW) infants to meet the intrauterine accretion rate for calcium and phosphorus. DESIGN: Comparison of currently formulated human milk fortifier with previous formulation. SETTING: Neonatal level II and III nurseries. PATIENTS: Twenty-six healthy, VLBW infants, whose mothers chose to breast-feed. INTERVENTIONS: We tested the effects of two formulations designed for VLBW infants as human milk supplements and differing primarily in their quantity and source of Ca, P, and magnesium. The study interval began with a milk intake of 100 ml.kg-1.day-1 and ended when a body weight reached 2.0 kg. MAIN OUTCOME MEASURES: Net absorption and retention of Ca, P, and Mg during a nutritional balance study conducted once during the study interval, growth during the entire study interval, and bone mineral content of the radius were measured at the beginning and end of the study interval. RESULTS: The newer Ca gluconate-glycerophosphate preparation (given to group CaGP) resulted in greater net absorption and retention of Ca and P (p < 0.01) than in infants given Ca phosphate (group CaTB). Mg retention was greater than (in group CaGP) or equivalent to (in group CaTB) the intrauterine accretion rate. Radius bone mineral content was significantly greater in group CaGP than in group CaTB (p < 0.001). Volumes of the fortified human milk preparation needed to meet the needs for gain in body weight were higher in group CaGP than in group CaTB (p < 0.001). CONCLUSIONS: Intrauterine accretion rates for Ca and P can be achieved when VLBW infants are fed human milk supplemented with Ca gluconate glycerophosphate. Supplementation of human milk with Mg may not be indicated. In this study, greater intakes of Ca and P, and not improvements in bioavailability, result in improved net retention and bone mineral content of VLBW infants. PMID- 7869209 TI - Diagnosis of neonatal enterovirus infection by polymerase chain reaction. AB - A 5-hour colorimetric polymerase chain reaction (PCR) assay was more sensitive than viral culture in identifying viral infection in initial serum (13/16 vs 5/16; p = 0.008) and urine (10/16 vs 5/16; p = 0.2) specimens from 16 enterovirus infected newborn infants, and remained more sensitive throughout their illnesses. Combined sensitivity of serum and urine PCR was 14 of 16 (88%). Results of all acute-phase PCR assays of serum and urine from four neonates with cultures negative for enterovirus were also negative. PCR assay of serum and urine facilitates rapid, accurate diagnosis of neonatal enterovirus infections. PMID- 7869210 TI - Inhaled nitric oxide for premature infants after prolonged rupture of the membranes. AB - We evaluated the use of inhaled nitric oxide in eight premature infants (520 to 1440 gm, 24 to 31 weeks of gestation) who failed to respond to conventional management and who had prolonged rupture of the membranes and oligohydramnios. All infants had a significant improvement in oxygenation and a fall in mean airway pressure with inhaled nitric oxide. Further studies are required to determine the safety and efficacy of this form of therapy. PMID- 7869211 TI - Intravenous morphine pharmacokinetics in pediatric patients with sickle cell disease. AB - To examine the pharmacokinetics of parenteral opioids, such as morphine, in patients with sickle cell disease, we determined the plasma morphine clearances in 18 patients (aged 6 to 19 years) who were receiving continuous intravenous infusions, and the pharmacokinetics of morphine in an additional six patients after single intravenous doses. Plasma morphine clearances ranged from 6.2 to 59.1 ml min-1 kg-1 (35.5 +/- 12.4, mean +/- SD) during steady-state infusions. There was a negative correlation between clearance values and age over the age range studied (p = 0.013). A significant difference (p = 0.042) was also observed in clearance values between patients who had serious adverse symptoms (23.4 +/- 10.7 ml min-1 kg-1) and those who had less serious symptoms (36.3 +/- 6.4 ml min 1 kg-1) when morphine was given at high dosage rates (> or = 0.15 mg kg-1 hr-1). Pharmacokinetic modeling of plasma morphine concentrations adequately fit a two compartment model with a short initial distribution phase (mean half-life = 4.5 minutes) and a rapid terminal elimination half-life (77.6 +/- 19.2 minutes). These findings suggest that considerable individualization of morphine dosing may be necessary to achieve optimal analgesia and minimal adverse effects in these patients. PMID- 7869212 TI - Combination treatment with growth hormone and gonadotropin-releasing hormone analogs in short normal girls. AB - To improve final adult height, we treated with growth hormone (0.65 +/- 0.07 (mean +/- SD) IU.kg-1.wk-1) and gonadotropin-releasing hormone analogs (66 +/- 9 micrograms.kg-1 every 28 days) a group of seven short normal girls in early puberty with a chronologic age (CA) of 11.50 +/- 0.95 years, predicted adult height (PAH) lower (0.003 < p < 0.001) than mean target height, and without any endocrine abnormalities. The results were compared with those obtained in a similar group of seven untreated girls considered as control subjects. The mean period of combined therapy was 2.01 +/- 0.52 years; in two subjects treatment is still in progress. The value of height standard deviation score for bone age (BA) improved from -1.69 +/- 0.47 to -1.04 +/- 0.56 (p = 0.001); height age (HA)/BA ratio also increased from 0.83 +/- 0.05 to 0.90 +/- 0.04 (p < 0.01), as did PAH (from 146.8 +/- 4.4 to 152.9 +/- 3.6 cm; p < 0.002). The ratio of gain in HA to gain in BA was 2.08 +/- 0.78. Pubertal stages showed an arrest in five cases and a regression in the other two girls. After administration of gonadotropin releasing hormone analogs was interrupted, in four of five girls growth hormone was administered alone for a further period of 6 to 18 months to improve their physiologic growth spurt. The present height in five girls is higher than PAH before therapy. In the treated girls the height values for BA, for BA/CA and HA/BA ratios, and for PAH were higher (0.002 < p < 0.04) than those in control subjects. This preliminary study demonstrates that combination therapy with growth hormone and gonadotropin-releasing hormone analogs in short, endocrinologically normal girls may be useful in improving both height prognosis and predicted adult height. Further studies are necessary to reach definitive conclusions regarding the efficacy of this kind of therapy. PMID- 7869213 TI - Response to growth hormone therapy in patients with growth hormone deficiency who at birth were small or appropriate in size for gestational age. AB - OBJECTIVE: To determine long-term growth response to growth hormone (GH) therapy in patients with isolated GH deficiency who had been small for gestational age and in those who had been appropriate in size for gestational age. DESIGN: Longitudinal, case-control study. SETTING: Pediatric clinic, endocrinology center, University of Bologna, Italy. PATIENTS: Sixteen GH-deficient children, small for gestational age with unknown cause, and 16 GH-deficient children, appropriate in size for gestational age, who were matched for chronologic age, bone age, pubertal stage, and target height at the beginning of treatment and were treated for 36 months. INTERVENTION: Recombinant human GH given subcutaneously at a dose of 20 IU/m2 per week in six doses per week for 36 months. MEASUREMENTS: Growth hormone levels (fluoroimmunoenzymatic method), levels of insulin-like growth factor I (radioimmunoassay), and complete 36-months auxologic follow-up. RESULTS: Patients who were small for gestational age had a modest improvement in height for chronologic age but no increase in predicted final height. Patients who were appropriate in size for gestational age had significantly better improvement in both measurements (multivariate analysis of variance: F = 6.3 (p < 0.001) and F = 3.8 (p < 0.05), respectively). Catch-up growth was similar during the first year of therapy for the two groups, after which the linear growth velocity decreased more rapidly in the small-for gestational-age patients (multivariate analysis of variance: F = 4.9 (p < 0.05)). CONCLUSIONS: The constitutional component of the statural deficiency of small-for gestational-age children seemed to prevail over hormonal deficiency during treatment with GH. Further follow-up to final height is necessary to evaluate these different responses. PMID- 7869214 TI - Effect of growth hormone therapy on final versus predicted height in short twelve to sixteen-year-old boys without growth hormone deficiency. AB - The effect of growth hormone therapy on final height in 28 short boys without growth hormone deficiency was evaluated retrospectively. The boys had received growth hormone for at least 2 years and were close to final height when therapy was stopped. The mean estimated final height was very close to that predicted from the pretherapy bone age. The fact that bone age advanced a mean of 4.9 years during a mean of 3.5 years of therapy may account for the lack of effect on final height. PMID- 7869215 TI - Otitis media, hearing sensitivity, and maternal responsiveness in relation to language during infancy. AB - The relation of otitis media with effusion (OME) and associated hearing loss to language and cognitive skills at 1 year of age was studied to determine whether OME-related hearing loss had a direct association with language and cognitive outcomes at 1 year of age or an indirect association with these outcomes, as mediated by the child-rearing environment. Subjects were 61 black infants attending community-based child care programs. The presence of OME was assessed biweekly from 6 to 12 months of age by otoscopy and tympanometry. Hearing was assessed with visual reinforcement audiometry when children were well and when ill with OME. Language and cognitive skills and the child-rearing environment at home and in child care were examined. The results indicated a modest correlation between hearing loss associated with OME and receptive language. However, the direct association between OME-related hearing loss and all the language and cognitive measures was negligible. Hearing loss had an indirect association with receptive and expressive language, cognitive development, and overall communication as mediated by child-rearing factors. That is, children with more frequent hearing loss tended to have less responsive mothers and home environments, and this association was linked to lower performance on the infant assessments. PMID- 7869216 TI - Bacteriuria in children with neurogenic bladder treated with intermittent catheterization: natural history. AB - OBJECTIVE: To determine whether bacteriuria unassociated with symptoms in patients with neurogenic bladder will lead to symptomatic infection and/or deterioration of the upper urinary tract if left untreated, we examined whether bacteriuria persisted in bladder urine of children with neurogenic bladder treated with clean intermittent catheterization (CIC) and whether persistence of bacteria led to symptomatic infection or deterioration of the upper urinary tract. DESIGN: Weekly home visits were made during 6 months of surveillance of 14 children on the CIC regimen with a normal upper urinary tract and no reflux (as determined by renal ultrasonography, voiding cystourethrography, and serum creatinine measurement). During visits a sample of bladder urine was obtained by CIC, and signs and symptoms of urinary tract infection and all medications were recorded. RESULTS: Fourteen children were observed for 323 weeks. Cultures of 70% (172/244) of the urine samples collected were positive for organisms (> or = 10(4) colony-forming units per milliliter), 152 (88%) for the usual pathogens and 20 (12%) for commensal organisms. Bacteriuria was associated with pyuria two thirds of the time, regardless of bacterial species. Carriage of the same pathogen for 4 weeks or longer, with associated pyuria, was common during surveillance. Despite frequent episodes of bacteriuria with associated pyuria, there were only five symptomatic infections during the 323 patient-weeks. Children remained clinically well during the study period, and their upper urinary tract did not deteriorate. CONCLUSION: Bacteriuria persists for weeks in symptom-free children being treated with CIC for neurogenic bladder associated with a normal upper urinary tract. Before attempts are made to eradicate bacteriuria, treatment should be proved to be beneficial to this population. PMID- 7869218 TI - Band neutrophil counts in neonates. PMID- 7869217 TI - Isolation of Ureaplasma urealyticum from low birth weight infants. PMID- 7869219 TI - Electrocardiographic findings in Rett syndrome. PMID- 7869220 TI - Harm reduction: an emerging new paradigm for drug education. AB - Harm reduction is a new paradigm now emerging in the field of drug education. This strategy recognizes that people always have and always will use drugs and, therefore, attempts to minimize the potential hazards associated with drug use rather than the use itself. The rationale for a harm reduction strategy is presented, followed by an example of the kind of needs assessment which may be needed for planning a harm reduction strategy. PMID- 7869221 TI - Network commercials promote legal drugs: outnumber anti-drug PSA's 45-to-1. AB - During the week of September 16 to 22, 1990, commercials promoting drugs and alcohol outnumbered the networks' news stories, documentaries, and PSA's about illegal drugs by a ratio of almost 39-to-1. If you consider the PSA's alone, the commercials promoting drugs and alcohol outnumbered them by a ratio of almost 45 to-1. PMID- 7869222 TI - Drugs and guns among inner-city high school students. AB - Despite public and governmental concern about the issue, little has occurred in the way of a systematic assessment of the gun-possession profiles of young persons involved in the use and distribution of drugs. This article reports the results of an analysis of survey data collected from male, inner-city high school students. The data pertain to firearms possession and carrying, use of heroin, cocaine, and crack, the sale of drugs, and commission of crimes with weapons. The findings offer no evidence of a progressive, linear relationship between level of drug use and gun possession (including number of guns owned and the routine carrying of guns). However, disregarding level of drug use, when non-users were compared with users, and "heavy" users were compared with those who did not use drugs "heavily," significant differences in involvement in gun possession did appear. As well, when we separated students who did not sell drugs from those who did, the latter generally exhibited higher involvement in gun possession. Finally, drug sellers who also committed crimes with weapons exceeded drug sellers who did not in involvement in some, but not all, types of gun possession. PMID- 7869223 TI - Socio-demographic profile of substance users seeking treatment. AB - This study was conducted to obtain a personality profile and a descriptive analysis of a typical substance user who is presently enrolled in a treatment center and is receiving professional help for his or her substance use at one of four participating treatment centers in a southwestern city in the United States. According to the findings, a typical substance abuser is a thirty-one year old male who is third born and has parents who are more frequently non-professional. Most respondents became involved with substance use because of peer influence and reported feeling bored/unhappy. First substance use experiences were more frequently with marijuana, although at the time of enrollment at the treatment center, alcohol, cocaine/crack, heroine, marijuana, and a combination of substances were typically used. When ranking the major problems they perceive having in their lives, respondents reported most frequently, substance use and being bored/unhappy in life. When assessing respondent's family type, a difference was found between the balanced and midrange families when considering their plans on having children. Of the substance using respondents, most were planning children in their lives and of this group, many were from extreme (low functioning) families. PMID- 7869224 TI - Polydrug use and self control among men and women in prisons. AB - This article describes research conducted to examine the patterns of alcohol and drug use and self concepts of incarcerated adult offenders in relation to age, gender, and ethnicity in a western state. The purpose of this research was to estimate the extent and variety of alcohol and drug use in the prison population and design a data collection instrument. Individual interviews with every newly admitted sentenced felon (N = 157 men and 39 women) were conducted. Inmates reported nearly universal alcohol use and marijuana use and extensive use of cocaine, crack, heroin, crystal methamphetamine (ice) and using various other schedule drugs, usually in combination with alcohol and other drugs. The problem for the interviewers was not how to elicit admissions of drug use but how to categorize the large number of combinations. Polydrug use, often in combination with alcohol, is the rule, not the exception. Starting, switching and quitting, and combining or substituting drugs is reported by the vast majority of inmates. While patterns varied, it was difficult to discern a special class of drug addicts among the inmates. Our findings suggest that large percentages of prison inmates are frequent substance abusers, perceive problems from use, but are often not interested in drug treatment in prison. Many inmates who by their own reports seem appropriate for alcohol or drug treatment do not seek treatment. This is not influenced by the extent of drug use or experience with previous treatment. Female prisoners seem to be more often and more extensively involved in addicting drugs than male prisoners. This is particularly problematic because there are very few specialized treatment or training programs for women offenders. Since drug use is very widespread, urine monitoring is increasing and continued criminalization of all drugs except alcohol enjoys wide support, correctional agencies must search to develop effective and affordable strategies for dealing with drug use. PMID- 7869225 TI - Messages discriminated from the media about illicit drugs. AB - The electronic media have been an instrumental tool in the most recent efforts to address the issue of illicit drug abuse in the United States. Messages about illicit drugs appear in three places in the media: advertising content, news content, and entertainment content. Many studies have documented the amount and types of messages that appear on the electronic media, but few have asked the audience how they interpret these messages. The purpose of this study is to investigate how much and what type of information college students receive from the media about drugs. Interviews were conducted with 228 students using the message discrimination protocol. The messages were then content analyzed into theme areas. Results indicate the majority of messages discriminated from advertising content were fear appeals; that the majority of messages discriminated from news content documented the enforcement efforts in the war on drugs; and that messages about drugs in entertainment content were more likely to provide clear accurate information about drugs than the other two content sources. The results are discussed in terms of the audience receiving fear and fight messages from the electronic media rather than clear, accurate information necessary to make informed decisions about drugs. PMID- 7869226 TI - The D'Youville College Campus School: alcohol collaboration or how to provide alcohol awareness at the elementary school level. PMID- 7869227 TI - Alcohol policies and free to be foolish: an analysis of college students. AB - A convenience sample of 472 undergraduate students from a large public university in the Midwest was surveyed with regard to their views on consumption of alcohol as a personal privilege and related policies on alcohol use. The sample of predominantly white students was divided between 239 libertarians and 192 supporters of collective responsibility. Compared with their collective peers, the libertarian students were younger, heavier consumers of alcohol, and more likely to be male. The libertarian students were opposed to external sanctions on drinking behavior regardless of source of authority. Intervention programs such as server training implemented by the students themselves were, however, supported by both groups. The potential for achieving wider low risk alcohol use through server training programs is considered in the context of campus and campus town life. Although promotion of such programs has potential for positive change, administrators must recognize the potency of the world view of "free to be foolish" and broader external forces when seeking a comprehensive needs-based approach to program planning. PMID- 7869228 TI - Effects of melatonin on microtubule assembly depend on hormone concentration: role of melatonin as a calmodulin antagonist. AB - Melatonin may play a key role in cytoskeletal rearrangements through its calmodulin antagonism. In the present work, we tested this hypothesis by studying melatonin effects on both microtubule polymerization in vitro and cytoskeletons in situ. Microtubule assembly is a dynamic process inhibited by Ca2+/calmodulin. Calmodulin antagonists prevent the inhibition by binding to Ca(2+)-activated calmodulin, thus causing microtubule enlargement. In the presence of calmodulin (5 microM) and CaCl2 (1 mM), polymerization at equilibrium was inhibited by 40%. Complete reversal of the Ca2+/calmodulin effect on microtubules was observed with 10(-9) M melatonin or with 10(-5) M trifluoperazine or 1 microgram/ml of compound 48/80. In the absence of Ca2+/calmodulin, melatonin at 10(-5) M inhibited tubulin polymerization like 10(-4) M trifluoperazine does. Melatonin effects on microtubule assembly at both nanomolar and micromolar ranges were corroborated in cytoskeletons in situ. Therefore, it is suggested that at a low concentration (10(-9) M), cytoskeletal melatonin effects are mediated by its antagonism to Ca2+/calmodulin. At a higher concentration (10(-5) M), non-specific binding of melatonin to tubulin occurs, thus overcoming the melatonin antagonism to Ca2+/calmodulin. The results support the hypothesis that under physiological conditions, melatonin synchronizes different body rhythms through cytoskeletal rearrangements mediated by its calmodulin antagonism. PMID- 7869229 TI - Clonidine in vivo mimics the acute suppressive but not the phase-shifting effects of light on circadian rhythm of serotonin N-acetyltransferase activity in chick pineal gland. AB - Comparative in vivo studies on effects of pulses of light and clonidine, a selective agonist of alpha 2-adrenergic receptors, on the circadian rhythm of serotonin N-acetyltransferase (NAT) activity in chick pineal gland were performed. Six-hour pulses of white light caused an acute suppression of the nocturnal NAT activity and phase-dependent phase shifts of the circadian rhythm of the enzyme activity relative to controls. Systemic administration of clonidine acutely suppressed NAT activity of chick pineal gland, but did not affect the phase of subsequent cycles in constant darkness. These results give further support to the concept based on in vitro studies that alpha 2-adrenergic receptors are involved in regulation of melatonin biosynthesis in chick pineal gland by a mechanism distal to the pacemaker that generates the circadian melatonin rhythm. PMID- 7869230 TI - Melatonin is involved in cholecystokinin-induced changes of ileal motility in rats. AB - The aim of this study was to determine, in the rat, the interaction between melatonin and cholecystokinin in the regulation of the ileal interdigestive motility. This was analyzed by the chronic electromyography technique. Ileal motility was defined by the presence of intermittent spike bursts corresponding to the contractile activity of the organ. In control rats, these spike bursts were organized in cyclic myoelectrical complexes. Each complex is characterized by two successive spiking activity phases: the irregular phase (ISA) followed by the regular phase (RSA). Pinealectomy suppressed the RSA phase so ileal motility was constituted only by the ISA phase. When melatonin (1 mg/kg i.v.) was injected into pinealectomized rats, RSA phases were immediately and definitively restored. RSA phases were also re-established when the "alimentary" type of cholecystokinin receptors (CCKA) were blocked by selective antagonists such as L364,718 or SR27897 (1 mg/kg i.v.). The latter had better brain accessibility than L364,718. Unlike the effects of melatonin, the effect of these antagonists was neither immediate (the latency is longer for L364,718 than for SR27897) nor definitive. In control rats, cholecystokinin (5 micrograms/kg i.v.) induced a characteristic long-lasting (29 +/- 2 min) excitomotor effect on the ileum. This effect was suppressed in pinealectomized rats and was restored after melatonin treatment. These results suggest that, via the central nervous system, melatonin is involved in the modulation of cholecystokinin action on ileal motility. PMID- 7869231 TI - Photoperiod and melatonin affect testicular growth in the marsh rice rat (Oryzomys palustris). AB - Reproduction in rice rats is subject to photoperiodic control and the pineal gland mediates this effect. We examined the effects of the pineal gland hormone melatonin on testicular weight when administered via implants, injections, and infusions. Testicular weight was modified by photoperiod and the size of the melatonin implant. Twenty-millimeter implants suppressed testicular weight in rice rats housed on 12- and 16-hr photoperiods, while those housed on a 14-hr photoperiod were more sensitive to melatonin; in these animals 10- and 20-mm implants inhibited testicular weight. Melatonin implants also prevented rice rats from responding to a change in photoperiod with the appropriate alteration of testicular growth. Melatonin injections inhibited testicular growth when administered before lights out on LD 14:10, but not on LD 16:8. Morning injections had no effect on either photoperiod. Finally, 12-hr duration melatonin infusions inhibited testicular growth in pinealectomized rice rats on LD 16:8, while 6-hr duration infusions were without effect. These data show that the pineal, through the secretion of melatonin, is a phototransducing organ intimately involved in testicular growth in rice rats. PMID- 7869232 TI - Inhibitory effect of melatonin on cataract formation in newborn rats: evidence for an antioxidative role for melatonin. AB - We evaluated the inhibitory effect of melatonin, a recently discovered scavenger of free radicals, on cataract formation in the newborn rat. The glutathione synthesis inhibitor, buthionine sulfoximine (BSO) (3 mmol/kg), was intraperitoneally injected into newborn rats for 3 consecutive days starting on day 2 after birth. These glutathione depleted rats develop cataracts. Melatonin (4 mg/kg) was injected intraperitoneally into half of the rats once a day beginning at day 2 after birth; the other half of the animals received solvent daily. The incidence of cataract was observed on day 16, after the eyes of the newborn animals had opened. Both reduced glutathione (GSH) and oxidized glutathione (GSSG) levels were measured. Cataracts were observed in all animals (18/18) treated with BSO plus solvent. The incidence of the cataract in the animals cotreated with melatonin was only 6.2% (1/15). Total lenticular glutathione (GSH + GSSG) levels in BSO only treated rats were reduced by 97%. The total glutathione in the lens of the BSO plus melatonin group was significantly higher (by 3%) than that of the BSO only group. The percentage of the total glutathione as GSSG for the BSO plus solvent group was higher than the control value. Cotreatment of BSO injected rats with melatonin (4 mg/kg/day) clearly reduced cataract formation proving that it is directly or indirectly protective against oxidative stress which accompanies glutathione deficiency. The inhibitory effects of melatonin on cataract formation in this study could be due to melatonin's free radical scavenging activity or due to its stimulatory effect on glutathione production. PMID- 7869233 TI - [Pharmaceutical dosage form design of copoly (lactic/glycolic acid) microspheres. Mechanism of in vitro release of gentamicin]. AB - The sustained release mechanism of gentamicin (GM) from lactic acid/glycolic acid copolymer (PLGA) microspheres was investigated. The terminal free carboxyl group of polymer was proved to be necessary for GM to be highly incorporated into microspheres by comparing interactions with GM and two types of polymers; free (ionized and non ionized) and the terminal esterified carboxyl group of polymer. The weight-average molecular weights (Mws) of component PLGAs of microspheres with an ionizable carboxyl group used here were approximately 4900 and 10000. The release pattern of GM was tested in phosphate buffered saline. The release rate of GM was dependent on the initial Mw and surface form. The GM release continued for 20 and 30 d from PLGA 4900- and PLGA10000-microspheres, respectively. The changes of total weight of microspheres tended to decrease with time, and the molecular weight distribution of PLGA gradually shifted to lower distribution, indicating a decrease in Mw. The changes and the shifts were dependent on the initial Mws of PLGAs but independent of their surface form. The half-times of wight loss of PLGA 4900- and PLGA10000-microspheres were about 10 and 20 d, respectively. From these results, the release profile of GM from PLGA microspheres was explained by the following three steps, i.e., 1) the release from the surface, 2) the relatively slow release caused by the obstruction of channels followed by the degradation of PLGA, 3) the release accompanied by the erosion of microspheres. PMID- 7869234 TI - [A quantitative determination of inducibility by 14 membered ring macrolide antibiotics in inducible resistant Staphylococcus aureus to macrolide-lincosamide streptogramin B antibiotics]. AB - Using Staphylococcus aureus ISP447 strain, which shows inducible resistance to macrolide-lincosamide-streptogramin B (MLS) antibiotics, the extent of MLS resistance induced by several macrolide antibiotics [erythromycin (EM), oleandomycin (OL), or roxithromycin (RXM)] was determined in terms of a relative ratio of a growth rate of the induced cells in the presence of a challenging drug, rokitamycin (RKM), to that of uninduced cells in the absence of RKM. The ratio was referred to as a relative inducibility (%). The inducibility was obtained at an optimum-induced condition by considering the following factors: (1) exponentially growing cells, (2) the optimum concentration of an inducer drug, i.e., 50, 150, and 150 ng/ml for EM, OL, and RXM, respectively, (3) a 3-h previous incubation at 37 degrees C in the presence of the inducer, and (4) 300 ng of RKM/ml, which is found to be optimum for induced cells to challenge, because of having no inducer activity. Using these qualification methods, inducibilities of EM, OL, and RXM as an inducer were 100.4, 27.9 and 81.1%, respectively. This method is allowed to be useful for the analysis of a structure inducibility relationship. PMID- 7869235 TI - [Research and development of ozagrel, a highly selective inhibitor of TXA2 synthase]. AB - Highly selective inhibitors of thromboxane (TX) A2 synthase were noted as a therapeutic agent for ischemic heart diseases, thromboembolic disorders, cerebral circulatory disorders, and asthma. The 1-substituted imidazoles and beta substituted pyridines showed high inhibitory potency on TXA2 synthase. The structure-activity relationships of the imidazole and pyridine derivatives as inhibitors of TXA2 synthase were investigated. Introduction of various substituents into the carboxy-bearing side chain of 1-(7-carboxyheptyl) imidazole and beta-(7-carboxyheptyl) pyridine was found to increase the inhibitory potency. The length of the side chains with the phenylene group was optimum in the region of 8.5 to 10 A for the inhibitory potency on TXA2 synthase. Among the tested imidazole and pyridine derivatives, (E)-4-(1-imidazolylmethyl)cinnamic acid (44) and (E)-3-[4-(3-pyridylmethyl)phenyl]-2-methylacrylic acid (56) showed the highest potency (IC50 = 1.1 x 10(-8) and 3 x 10(-9) M). The inhibition by these derivatives was highly selective for TXA2 synthase, since other enzymes which are involved in the arachidonic acid cascade, such as fatty acid cyclooxygenase, 5 lipoxygenase, prostacyclin (PGI2) synthase, and PGE2 isomerase were not affected. On the basis of the results obtained from the pharmacological, physicochemical and toxicological studies on the two compounds (44 and 56), (E)-4-(1 imidazolylmethyl) cinnamic acid (44; OKY-046, ozagrel) was selected as the best compound of highly selective inhibitors of TXA2 synthase. The pharmacological properties of ozagrel are as follows. The inhibition of TXA2 synthase by ozagrel was more effective on human and rabbit enzymes than those of other species. Ozagrel increased 6-keto-PGF1 alpha, one of stable metabolites of PGI2, in various isolated cells and tissues perhaps via accumulated PG endoperoxides resulted by the inhibition of TXA2 synthase. Such an increase in PGI2 production by ozagrel was also observed in various experimental animals. We obtained the suggestion that, by the reduction of TXA2 production and increment of PGI2 production, ozagrel inhibits the spasms of basilar artery and the decreases in regional cerebral blood flow in dogs which received autologous blood into cisterna magna, and inhibits the decreases in motor function and regional cerebral blood flow, and the formation of infarcted area in the animals of cerebral ischemic treatment. It was also suggested that ozagrel inhibits leukotriene-, platelet-activating factor-, and antigen-induced bronchoconstriction in guinea-pigs and inhibits the induction of airway hyperresponsiveness by various stimuli in several species of animals by both mechanisms. The summarized results of ADME, toxicological, and clinical studies were also described. PMID- 7869236 TI - [Kinetic analysis of the disposition of hydrophilic drugs in the central nervous system (CNS): prediction of the CNS disposition from the transport properties in the blood-brain and blood-cerebrospinal fluid barriers]. AB - The disposition of hydrophilic drugs in the central nervous system (CNS) was studied in relation to the transport properties across the brain capillaries which form the blood-brain barrier (BBB), and the choroidal epithelial cells which form the blood-cerebrospinal fluid (CSF) barrier, using beta-lactam antibiotics as model compounds. The concentration profiles for cefodizime in the rat CNS were analyzed based on a pharmacokinetic model in which the physiological and anatomical aspects of the CNS were considered. The model analysis revealed that the drug penetration into the CSF after i.v. administration can be accounted for by permeation across the BBB and diffusion through the brain extracellular fluid and across the ependymal surface into the CSF. The drug molecules are eliminated from the CSF by the bulk flow and by the active transport system in the choroid plexus. In in situ and in vivo experiments, we found that the beta lactam antibiotics are transported across the BBB via a carrier-mediated mechanism. Comparison of kinetic parameters determined in vivo and in vitro experiments revealed (1) that the choroid plexus is the predominant site for the elimination of beta-lactam antibiotics from the CSF and (2) that the isolated choroid plexus can be a useful tool to predict the in vivo elimination clearance. We also found that an anionic exchanger, at least in part, plays a role in the uphill transport of beta-lactam antibiotics in the choroid plexus. Furthermore, the substrate specificity for the anion transporter was examined in the isolated choroid plexus. New quinolones (such as fleroxacin) are also transported by the mechanism shared by beta-lactam antibiotics. Dideoxyinosine, a nucleoside derivative, can be a substrate for the transporter, whereas azidothymidine is recognized, but not transported by the transport system. Transport properties of cimetidine, a prototypic organic cation, in the choroid plexus was also characterized in vivo, in situ and in vitro experiments. An interaction was observed in the transport of cimetidine and that of organic anions. Molecular mechanisms for the CNS transport still remain to be clarified. PMID- 7869237 TI - [Protective effect and antibody titer of intravenous immunoglobulin (IVIG) against clinical isolates of opportunistic bacteria]. AB - Neonates and leukopenic, immunosuppressed patients are at high risk for severe infection of opportunistic pathogens despite of the availability of potent antimicrobial agents. In this study, antibody titers of immunoglobulin preparations (IVIG) were contrasted with the protective effect in mice against each of bacterial infection. Antibody titers were determined by ELISA. The antigens were 70-80 clinical isolates of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus, respectively. Antibody titers of IVIG against these three gram-negative bacteria ranged 3200 to 102,400. ICR mice were inoculated intraperitoneally with each of several strains against which IVIG showed various titers. IVIG showed rather high protective activities against well-reactive strains, while it showed little protective activities against poor-reactive strains. In the case of P. aeruginosa, statistical analysis of the results obtained with the antibody titer and efficacy showed a good correlation (p < 0.01). On the other hand, IVIG showed a high and complicate antibody titer against S. aureus IVIG ranging 400,000 to 12,800,000, since apparent titers contained non-specific binding of Fc portion of IgG with protein A on the cell wall. IVIG was active in mice, where protein A was less and specific binding was stronger. Bacterial cells have various components; lipopolysaccharide, lipid A, capsule, flagella, pill, etc. that are responsive to specific antibodies. This study indicates that IVIG have such antibodies and that is associated with protective activity against bacterial infection in proportion to antibody titer. PMID- 7869238 TI - [Studies on antiulcer agents. I. The effects of various methanol and aqueous extracts of crude drugs on antiulcer activity]. AB - The antiulcer activities of 59 methanol and aqueous extracts obtained from 59 crude drugs on the ethanol-HCl-induced ulceration in rats were investigated. Among them 15 extracts were selected and they were further examined for their effects on indomethacin-, aspirin- and the water-immersion stress-induced ulcer. From these results, the methanol extract of root of Iris germanica was found to, show potent antiulcer activities. The above methanol extract was separated into 3 portions by solvent extraction, and the ether soluble portion was fractionated into 5 fractions (1 to 5) by chromatography. Fractions 4 and 5 showed significant antiulcer activities. Fraction 4 was further purified and the obtained gamma irigermanal exhibited a potent antiulcer activity. However, further investigations are required to understand the mechanism. PMID- 7869239 TI - [Studies on antiulcer agents. II. Synthesis and antiulcer activity of phenylpropanol derivatives]. AB - It was found that gamma-irigermanal, obtained from the methanol extract of root of Iris germanica, exhibited a potent antiulcer activity. Therefore, this compound was selected as a lead-compound, and related compounds were synthesized and tested for antiulcer activities. It was found that (+/-) ethyl 2-[2-(3 hydroxypropyl)-4-oxocyclohexylidene]- propionate (1) had excellent antiulcer activities. Then phenylpropanol derivatives, obtained by changing from cyclohexane ring of 1 to benzene ring, were synthesized and tested for antiulcer activities in order to study structure activity relationships. As a result, (+/-) ethyl 2-[2-(3-hydroxypropyl)-4,5-dimethoxy-phenyl]propionate (2b) and (+/-) 3-[2 (3-hydroxypropyl)-4,5-dimethoxyphenyl]-2-butanone (5) were shown to have antiulcer activities. PMID- 7869240 TI - Effects of angiotensin II on intracellular Ca2+ and pH in isolated beating rabbit hearts and myocytes loaded with the indicator indo-1. AB - 1. Angiotensin II increases myocardial contractility in several species, including the rabbit and man. However, it is controversial whether the predominant mechanism is an increase in free cytosolic [Ca2+]i or a change in myofilament Ca2+ sensitivity. To address this question, we infused angiotensin II in isolated perfused rabbit hearts loaded with the Ca2+ indicator indo-1 AM and measured changes in beat-to-beat surface transients of the Ca2+i-sensitive 400:500 nm ratio and left ventricular contractility. The effects of angiotensin II were compared with the response to a Ca(2+)-dependent increase in the inotropic state produced by a change in the perfusate [Ca2+] from 0.9 to 3.6 nM. 2. In the isolated beating heart, an increase in perfusate [Ca2+] caused an increase in left ventricular pressure +dP/dt in association with an increase in peak systolic [Ca2+]i. Angiotensin II perfusion caused a similar increase in left ventricular +dP/dt in the absence of any increase in peak systolic [Ca2+]i. 3. To exclude any contribution of non-myocyte sources of Ca(2+)-sensitive fluorescence which may be present in the intact heart, we also compared the effects of angiotensin II and a change in superfusate [Ca2+] in collagenase-dissociated paced adult rabbit ventricular myocytes loaded with indo-1 AM. In the isolated rabbit myocytes a change in perfusate [Ca2+] from 0.9 to 3.6 mM caused an increase in peak systolic cell shortening coincident with an increase in peak systolic [Ca2+]i. In contrast, angiotensin II caused a similar increase in peak systolic cell shortening whereas there was no increase in peak systolic [Ca2+]i. There was also no change in inward Ca2+ current (ICa) in response to angiotensin II. 4. To investigate further the mechanism of the positive inotropic action of angiotensin II, its effects on intracellular pH were studied in isolated rabbit myocytes loaded with the fluorescent H+ probe SNARF 1. These experiments demonstrated that angiotensin II induced a 0.2 pH unit increase coincident with the development of a positive inotropic effect in isolated rabbit myocytes. 5. In summary, angiotensin II has a direct positive inotropic effect in beating rabbit hearts and in isolated paced rabbit myocytes. These experiments provide support for the hypothesis that the predominant mechanism is not an increase in free cytosolic Ca2+ but is due in part to an increase in myofilament Ca2+ sensitivity due to intracellular alkalosis. PMID- 7869241 TI - Inhibition of inwardly rectifying K+ current by external Ca2+ ions in freshly isolated rabbit osteoclasts. AB - 1. Regulation of membrane potential by extracellular Ca2+ concentration ([Ca2+]o) was examined in freshly isolated rabbit osteoclasts. 2. The resting membrane potential of osteoclasts was close to the K+ equilibrium potential in 1 mM Ca2+ medium. An elevation of [Ca2+]o caused membrane depolarization, accompanied by a decrease in the membrane conductance. 3. The inwardly rectifying K+ current observed under voltage clamp was dose-dependently inhibited by an elevation of [Ca2+]o, which explained the membrane depolarization caused by high [Ca2+]o. 4. Other divalent cations also inhibited the inwardly rectifying K+ current with the following order of potency: Ca2+ < Ni2+ < or = Co2+ < Cd2+. 5. In the presence of intracellular GTP gamma S the inwardly rectifying K+ current was irreversibly inhibited by [Ca2+]o, whereas the inhibition of the inwardly rectifying K+ current was greatly attenuated by intracellular application of GDP beta S. 6. Pertussis toxin (PTX) treatment did not abolish the inhibition of the inwardly rectifying K+ current caused by [Ca2+]o. 7. These results suggest that inwardly rectifying K+ channels in osteoclasts were regulated by a PTX-insensitive G protein, which was coupled to the putative Ca2+ receptor or sensor on the cell membrane. PMID- 7869242 TI - Regulation of K+ conductance by histamine H1 and H2 receptors in neurones dissociated from rat neostriatum. AB - 1. The effects of histamine on dissociated neostriatal neurones of the rat were investigated in the whole-cell mode using the nystatin-perforated patch recording technique. 2. Histamine evoked a net inward current accompanied by a decrease in the membrane conductance at a holding potential (Vh) of -44 mV. This response was observed in neurones considered to be interneurones based on morphology, membrane properties and the responsiveness to acetylcholine. 3. A net inward current evoked by 10(-8) to 10(-6) M histamine was inhibited in a concentration-dependent manner by the H1 receptor antagonists, pyrilamine and triprolidine. The H1 receptor agonists, 2-methylhistamine and 2-thiazolylethylamine, mimicked the histamine response, indicating that this response was mediated by the H1 receptor. 4. Histamine, at high concentrations between 10(-6) and 10(-5) M, evoked an additional net inward current with a decrease in the membrane conductance, which was inhibited by the H2 receptor antagonists, cimetidine, ranitidine and famotidine. The H2 receptor agonist, impromidine, partially mimicked the response. Thus, this additional current was considered to be mediated by the H2 receptor. 5. The reversal potentials for H1 and H2 receptor operated currents shifted 56.9 and 59.3 mV for a 10-fold change in [K+]o, respectively, suggesting that these currents were carried by K+. 6. An analysis of change in current fluctuations mediated by H1 and H2 receptors suggested that the unitary current amplitudes of K+ channels linked to H1 and H2 receptors were 0.29 +/- 0.06 (n = 4) and 0.27 +/- 0.07 pA (n = 4), respectively. There was no significant difference between these values. The estimated mean life times (tau) for both channels were also identical (1.1 ms). 7. It was concluded that histamine reduces K+ currents in neostriatal interneurones and that both H1 and H2 receptors are involved in the response. PMID- 7869243 TI - Position-dependent expression of potassium currents by chick cochlear hair cells. AB - 1. Potassium currents in chick cochlear hair cells were studied using whole-cell voltage clamp techniques. Cells were isolated from 200 microns-long segments of the apical half of the cochlea. In each segment, expression of potassium currents by cells positioned across the width ('inner-outer' hair cell axis) of the cochlea was examined. 2. A rapidly inactivating potassium current (IA) was found in some hair cells. At a membrane potential of -24 mV, IA activated to peak values within 7 +/- 1 ms and inactivated within 73 +/- 16 ms. The activation 'threshold' was around -50 mV and hyperpolarization more negative than -56 +/- 5 mV was required before significant removal of inactivation occurred (V 1/2 (half inactivation potential) = -74 +/- 5 mV). The resting potential of cells with IA was -46 mV +/- 11 mV. This current was blocked by 4-aminopyridine with a Kd of 0.45 mM. 3. Cells that were isolated from the most apical tip of the cochlea expressed no IA. In areas more basal than 200 microns from the apex, the magnitude of IA correlated with cell morphology. In each area, the tallest hair cells (cells with the smallest ratio of apical surface diameter to length) had none of this current. Of the cells with IA, the shorter cells (larger ratio of apical surface diameter to length) had more of this current. 4. The magnitude of IA in a cell was dependent upon cross-cochlear position, and the relationship between IA and cell morphology was most probably a reflection of a differential distribution of cell shape across the cochlea. The tallest hair cells, occupying roughly the first 40% of the distance from the neural side of the basilar papilla, had no IA. Of the remaining cells, those nearer to the abneural edge expressed more IA, such that iso-magnitude lines ran approximately parallel to the long axis of the cochlea. 5. A delayed rectifier current (IK) and an inward rectifier current (IIR) were also differentially distributed among hair cells across the cochlea; however, their distribution differed from that of IA. IK and IIR were preferentially expressed by the taller hair cells, which were positioned nearer to the neural side of the cochlea. Ca(2+)-activated potassium current (IK(Ca)) did not vary systematically between cells of different shape or cross cochlear position, and IK(Ca) could often be found in cells with IA. PMID- 7869244 TI - Sensory input and burst firing output of rat and cat thalamocortical cells: the role of NMDA and non-NMDA receptors. AB - 1. Intracellular and patch-clamp recordings were obtained from thalamocortical (TC) cells in the rat and cat dorsal lateral geniculate nucleus (dLGN) in vitro to study the role of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the synaptic potential and burst firing evoked by electrical stimulation of the optic tract. 2. At membrane potentials more positive than -65 mV, the sensory synaptic potential consisted of a fast EPSP that was followed by a smaller, slower component. At membrane potentials more negative than -65 mV, this slower component became more prominent owing to the presence of a low-threshold (LT) Ca2+ potential, which in turn evoked a high-frequency (> 150 Hz) burst of action potentials. The lower, but not the upper limit of the range of membrane potential over which burst firing occurred was dependent on the amplitude of the fast EPSP. 3. The non-NMDA receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM) and 1-(4-amino-phenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3- benzodiazepine (GYKI 52466, 100 microM) greatly depressed the fast EPSP, abolished the burst firing generated by the LT Ca2+ potential, and left a relatively small, slow EPSP, which was sensitive to the NMDA antagonist DL-2 amino-5-phosphonovaleric acid (DL-AP5, 50-100 microM). 4. In the absence of CNQX or GYKI 52466, DL-AP5 depressed the slow but not the fast EPSP. DL-AP5 also increased the latency of the first action potential evoked by the LT Ca2+ potential or even abolished the LT Ca2+ potential and associated burst firing. The latter effect was only present when this type of firing occurred within a small membrane potential range. 5. DL-AP5 had no effect on the properties of the LT Ca2+ current IT, indicating that its effect on the burst firing was not mediated by a direct action on IT. 6. The response of TC cells to high-frequency (100 Hz) stimulation consisted of an initial burst firing response, followed by a sustained depolarization that could reach firing threshold. This sustained depolarization was markedly depressed by DL-AP5 but not by CNQX. 7. These results demonstrate that with low-frequency stimulation of the sensory afferents, the generation of TC cell output in the rat and cat dLGN is mainly controlled by non NMDA receptors, while the contribution of NMDA receptors is limited to the burst firing generated by the LT Ca2+ potential, and depends on the membrane potential range over which this type of firing occurs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7869245 TI - The effects of hyperglycaemic hypoxia on rectification in rat dorsal root axons. AB - 1. Electrotonic responses to 150 ms current pulses were recorded from isolated rat dorsal roots incubated for at least 3 h with either normal (5 mM) or high (25 mM) D-glucose solutions, and with either normal (25 mM) or low (5 mM) bicarbonate concentrations. 2. On replacement of O2 by N2 for 50 min, all the roots depolarized, but the changes in electrotonus differed systematically. With normal glucose, the depolarization was accompanied by an increase in input conductance. In contrast, for the hyperglycaemic roots the depolarization was slower and accompanied by a fall in input conductance which was exacerbated in low bicarbonate concentrations. 3. The changes induced by hyperglycaemic hypoxia in low bicarbonate could be mimicked by exposure of the roots either to 100% CO2 or to a combination of 3 mM tetraethylammonium chloride and 3 mM 4-aminopyridine, to block both fast and slow potassium channels. 4. These results indicate that the primary mechanism of hypoxic depolarization of these sensory axons is altered by hyperglycaemia. In normoglycaemia, the changes in electrotonus are consistent with an increase in axonal potassium conductance. The block of potassium channels seen in hyperglycaemic hypoxia is attributed to intra-axonal acidification by anaerobic glycolysis and may contribute to the pathogenesis of diabetic neuropathy. PMID- 7869246 TI - Activity of bulbar respiratory neurons during fictive coughing and swallowing in the decerebrate cat. AB - 1. The behaviour of medullary respiratory neurons was studied during fictive coughing and swallowing evoked by electrical stimulation of the superior laryngeal nerve (SLN) in decerebrate, paralysed and artificially ventilated cats. Fictive coughing, swallowing and respiration were monitored by recording activities of the phrenic, hypoglossal and abdominal nerves. 2. Extracellular recordings were made from respiratory neurons in the ventral respiratory group (VRG) and in the Botzinger complex (BOT). The neuronal types analysed included decrementing inspiratory neurons (I-DEC), augmenting expiratory neurons (E-AUG) and decrementing expiratory neurons (E-DEC) from the BOT area, and augmenting inspiratory neurons (I-AUG) and augmenting expiratory neurons (E-AUG) from the VRG area. 3. During fictive coughing, all the inspiratory and expiratory neurons were active during the inspiratory and expiratory phases of coughing, respectively. The firing of both I-DEC and I-AUG neurons was increased and prolonged in association with the augmented inspiratory activity of the phrenic nerve. The activity of E-AUG neurons of the VRG did not parallel the abdominal nerve activity, suggesting the existence of additional neurons which participate in the generation of abdominal nerve activity during fictive coughing. 4. During fictive swallowing, half of I-DEC neurons fired transiently at the onset of hypoglossal bursts associated with swallowing; the firing was suppressed during the rest of the hypoglossal bursts. Other I-DEC neurons were silent during hypoglossal bursts. Some I-AUG neurons fired during the initial half of hypoglossal bursts, and others were silent. The brief phrenic activity accompanying the swallowing might have originated from this activity in I-AUG neurons. The discharges of all E-AUG neurons (BOT and VRG) and the majority of E DEC BOT neurons were suppressed during swallowing. 5. We conclude that these five types of respiratory neurons of the BOT and VRG are involved in the generation of the spatiotemporally organized activity of coughing and swallowing, and that at least a part of the neuronal network for respiration is shared by networks for these non-respiratory activities. PMID- 7869247 TI - Sympathetic and parasympathetic interaction in vascular control of the nasal mucosa in anaesthetized cats. AB - 1. In cats anaesthetized with pentobarbitone sodium (45 mg kg-1), electrical stimulation of the parasympathetic nerve fibres to the nasal mucosa evoked frequency-dependent increases in nasal arterial blood flow whereas stimulation of the superior cervical sympathetic nerve induced marked vasoconstriction. 2. Sympathetic nerve stimulation for 3 min at 10 Hz evoked significant (P < 0.05) and prolonged (> 30 min) attenuation of the vasodilatory response to subsequent parasympathetic stimulation. 3. Combined pretreatment with adrenergic and cholinergic blockers reduced the vasoconstrictory effect of sympathetic stimulation by 28 +/- 4% (mean +/- S.E.M.) and the parasympathetically evoked vasodilatation by 20 +/- 5%. 4. The vasodilatory effects of exogenous vasoactive intestinal polypeptide, peptide histidine isoleucine and galanin, and the vasoconstrictory effects of exogenous neuropeptide Y (NPY) and alpha,beta methylene adenosine 5'-triphosphate were not altered by adrenoceptor antagonists and atropine whereas the effects of exogenous noradrenaline and acetylcholine were virtually abolished. 5. The atropine-resistant parasympathetic vasodilatation remained significantly attenuated for more than 30 min after the non-adrenergic sympathetically evoked vasoconstriction. 6. Exogenous NPY (25 x 10(-9) mol) mimicked the effect of sympathetic stimulation in attenuating subsequent parasympathetically evoked vasodilatation. PMID- 7869248 TI - Electrophysiological studies of the interaction between ventricular myocardium and coronary artery in monkeys. AB - 1. The electrical influence of the coronary arteries on ventricular muscle was investigated using strips of ventricle that included a section of coronary artery (cardiac preparation) and isolated coronary arteries dissected from the ventricle (arterial preparation). 2. In cardiac preparations, a hyperpolarizing response was recorded from the epicardial surface of the ventricular muscle when acetylcholine (ACh) was added to the organ bath, on condition that the internal diameter of the coronary artery was between 0.15 and 0.6 mm, that the vessel ran at a depth of 0.2 mm or less below the surface of the preparation, and that the recording microelectrode was immediately adjacent to the artery. 3. ACh-induced hyperpolarization was not detected in cardiac preparations which had no detectable arteries, or at sites distant from visible arteries. 4. In arterial preparations, a similar hyperpolarizing response was evoked by ACh in all vessels with an i.d. of 0.15-1.2 mm. 5. In a preparation combining ventricular muscle and a strip of coronary artery (with the vascular endothelium in direct contact with the epicardial surface of the ventricular myocardium), hyperpolarization was also observed from the ventricular muscle after application of ACh. 6. The hyperpolarizing response of the ventricular myocardium in the cardiac preparation and in combined preparations of ventricular muscle and coronary artery was weakened or abolished by removal of the arterial endothelium. 7. These results indicate that some substance released from the coronary arterial endothelium after stimulation by ACh induces hyperpolarization of the ventricular myocardium. PMID- 7869249 TI - Cardiac contraction and intramyocardial venous pressure generation in the anaesthetized dog. AB - 1. Two hypotheses relating to the influence of contraction of the heart on coronary venous pressure (Pv) were tested. The first assumes a direct transmission of left ventricular pressure (PLV). According to the alternative hypothesis the Pv is caused by cyclical changes in the elastance of the surrounding tissue. 2. A small epicardial vein was cannulated retrogradely in eight open-chest dogs deeply anaesthetized with fentanyl. The duration of diastoles was varied after induction of a heart block with formaldehyde. Coronary arterial inflow and perfusion pressure were controlled by a perfusion system connected to the left main coronary artery by a Gregg cannula. Stopped-flow Pv was studied with intrinsic coronary tone (IT) and after maximal dilatation with adenosine. 3. The Pv pulse in the first contraction after a long diastole was not significantly correlated to the PLV pulse, with a slope of 0.5, in any dog, either with IT or during adenosine treatment. Comparing the first contraction after the long diastole with the last beat before, systolic Pv pulse decreased significantly in seven out of eight dogs, but systolic PLV pulse increased in five dogs and was unaltered in three dogs in both conditions. In contrast, end diastolic Pv was significantly correlated to the systolic Pv in each individual animal under either condition. 4. The results indicate that pressure generation in the small coronary veins can be explained on the basis of the time-varying elastance hypothesis and that a direct transmission of PLV to Pv is absent. PMID- 7869250 TI - Dynamic asymmetries of cardiac output transients in response to muscular exercise in man. AB - 1. We determined the kinetics of cardiac output (Q) with respect to oxygen uptake (VO2) at the on- and off-transients of constant-load exercise. Six subjects performed constant-load exercise which consisted of 5 min rest, 5 min one-legged pedalling at 50 W and a 5 min recovery period. 2. The transient responses were characterized by first-order kinetics. There was no significant difference between the time constants for VO2 (tau VO2) at the on- (33.9 +/- 3.5 s, mean +/- S.E.M.) and off-transient (37.2 +/- 2.9 s). The time constant for Q (tau Q, 29.4 +/- 3.2 s) was consistently shorter than tau VO2 at the on-transient. However, tau Q was appreciably longer at the off-transient (44.3 +/- 3.6 s) than the on transient. 3. The results support the contention that the time constant for the on-transient of Q is appreciably faster than that for VO2 and hence there seems little justification for the notion that the time constants for the kinetics of VO2 are determined by the limitations of blood flow in the transient. The asymmetry of Q kinetics, with the off-transient tau Q being appreciably slower than the on-transient tau Q, serves to maintain a sufficiently high oxygen flow to the muscle during recovery from exercise at a time when the muscle oxygen uptake remains high. PMID- 7869251 TI - Nitric oxide contributes to the rise in forearm blood flow during mental stress in humans. AB - 1. Our aim was to determine whether the vasodilating substance nitric oxide (NO) contributes to the rise in forearm blood flow observed during mental stress in humans. We also determined whether the NO might be released as a result of cholinergic stimulation of the vascular endothelium. 2. Blood flow was measured in both forearms using plethysmography during several 3-5 min bouts of a colour word test. In one forearm the nitric oxide synthase blocker NG-monomethyl-L arginine (L-NMMA) and other drugs were infused via a brachial artery catheter. The contralateral forearm served as a control. 3. When L-NMMA was given prior to mental stress it blunted the rise in blood flow in the treated forearm almost completely. The normal blood flow response returned during a second bout of stress conducted after a wash-out period. During a third bout of mental stress, administration of more L-NMMA again blunted the blood flow responses to mental stress. 4. When atropine was given prior to mental stress, the increases in blood flow were reduced in the treated forearm. Subsequent administration of both atropine and L-NMMA caused a somewhat greater reduction in the blood flow responses than those observed with atropine alone. 5. These data demonstrate that NO plays a role in forearm vasodilatation during mental stress in humans. It is likely that most of the NO is released by cholinergic stimulation of the vascular endothelium. PMID- 7869252 TI - Human spinal lateralization assessed from motoneurone synchronization: dependence on handedness and motor unit type. AB - 1. Motoneurone synchronization as a means of investigating synaptic connectivity was studied in the extensor carpi radialis muscles of the preferred and non preferred arms of healthy right- and left-handed human subjects. The activities of pairs of motor units recorded during voluntary isometric contractions were analysed by cross-correlation to detect any synchronous motor unit firing in the form of central peaks in the cross-correlation histograms. 2. The synchronization peaks were compared first in the case of 273 motor unit pairs tested in the preferred and non-preferred arms of two left-handed subjects and two right-handed subjects. The percentage of synchronized motor unit pairs was found to be significantly higher in the preferred arm with synchronization peaks significantly larger and broader than in the non-preferred arm. The narrow peaks (< 7.5 ms) likely to reflect the activity of common inputs to motoneurones were also found to be significantly larger in the preferred arm of all four subjects. 3. The handedness-related differences in synchronization were definitely confirmed in a total of 275 pairs of motor units tested in the left extensor carpi radialis muscles of fourteen right-handed subjects using their non preferred arm and six left-handed subjects using their preferred arm. In order to determine whether the differences in synchronization were dependent on the motor unit type, each motor unit was characterized on the basis of its recruitment threshold and on the basis of the contraction time of its twitch extracted from the overall muscle force using the spike-triggered averaging method. Two populations of motor units were distinguished, namely the 'slow' motor units (recruitment thresholds < 0.4 N, contraction times > 40 ms) and the 'fast' motor units (recruitment thresholds > 0.6 N, contraction times < or = 40 ms). 4. In the non-preferred arm, the synchronization peaks were always fairly narrow, whatever the motor unit's biomechanical properties; whereas in the preferred arm, broad peaks were found to be particularly common among the pairs including one or two fast motor units, which also showed the largest rate of synchronization occurrence. 5. The narrow peaks (< 7.5 ms) were found to be consistently larger in the preferred than the non-preferred arm whatever the categories of motor unit pairs. In both arms, however, the amplitude of the narrow peaks tended to increase as the recruitment threshold of the motor unit decreased and as their contraction time increased.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7869253 TI - Sensitization of insensitive branches of C nociceptors in human skin. AB - 1. Eighteen cutaneous mechanosensitive C nociceptors were recorded from the peroneal nerves of healthy human subjects. Their identity was continuously monitored by intracutaneous electrical stimulation, and their activation by mechanical or transcutaneous electrical stimulation was detected by slowing of conduction velocity during the relative refractory period. 2. Mechanoreceptive fields (mRFs) mapped with suprathreshold von Frey hair stimuli covered an area of 99 +/- 21 mm2 (mean +/- S.E.M.). Two of the units had separate mRFs, with borders about 0.5-1.5 cm apart from each other and the largest of these units had a maximal diameter of 4.5 cm. 3. Successive topical application of mustard oil and capsaicin induced expansions of mRFs by 57 +/- 14 mm2 in eight of fifteen units. 4. In twelve units transcutaneous electrical stimulation delivered through a pointed electrode was used for mapping the electroreceptive fields (eRFs). The borders of the eRFs and the mRFs were identical for two of twelve units only. In the other ten units additional mechano-insensitive areas (55 +/- 22 mm2) were detected from which transcutaneous electrical stimuli could activate the respective unit. 5. Application of mustard oil and capsaicin to these mechano insensitive areas sensitized five of eight units to mechanical stimuli. In these cases the mRF after sensitization exactly corresponded to the eRF. 6. It is concluded that there are insensitive branches in human mechanosensitive cutaneous C nociceptors that can be detected by transcutaneous electrical stimulation and sensitized by topical application of chemical irritants. Activation of those branches in the course of inflammatory processes may contribute to spatial summation at central synapses and hence to hyperalgesia. PMID- 7869255 TI - Na+ channel mis-expression accelerates K+ channel development in embryonic Xenopus laevis skeletal muscle. AB - 1. The normal developmental pattern of voltage-gated ion channel expression in embryonic skeletal muscle cells of the frog Xenopus laevis was disrupted by introduction of cloned rat brain Na+ channels. 2. Following injection of channel mRNA into fertilized eggs, large Na+ currents were observed in muscle cells at the earliest developmental stage at which they could be uniquely identified. Muscle cells normally have no voltage-gated currents at this stage. 3. Muscle cells expressing exogenous Na+ channels showed increased expression of at least two classes of endogenous K+ currents. 4. This increase in K+ current expression was inhibited by the Na+ channel blocker tetrodotoxin, suggesting that increased electrical activity caused by Na+ channel mis-expression triggers a compensatory increase in K+ channel expression. 5. Block of endogenous Na+ channels in later control myocytes retards K+ current development, indicating that a similar compensatory mechanism to that triggered by Na+ channel mis-expression operates to balance Na+ and K+ current densities during normal muscle development. PMID- 7869254 TI - Stable human standing with lower-limb muscle afferents providing the only sensory input. AB - 1. This study investigated the sources of sensory information upon which normal subjects' ability to stand depends. 2. An 'equivalent body' was used to simulate the physical properties of each subject's body during standing. The modulation of ankle torque required to support the equivalent body in an upright position was similar to that required to support the subject's own body when standing. However, when balancing the equivalent body, vestibular inputs were excluded from directing the appropriate changes in ankle torque. Thus, stability of stance could be studied with (normal stance) and without (balancing equivalent body) modulation by vestibular inputs. Vision could be excluded by closing the eyes. Sensory input from the feet and ankles could be removed by local anaesthesia from prolonged ischaemia, induced by occluding blood flow with inflated pneumatic cuffs just above the ankles. With vestibular, visual and peripheral sensory inputs negated, standing could rely only upon remaining sensory inputs, notably those from sensory receptors in the leg muscles. 3. Unlike the human body, the equivalent body used to negate vestibular inputs is not segmented. Therefore, the effects on stability of having a segmented body were determined by splinting subjects during standing so that only ankle movement was possible. This was done in the presence and absence of visual stabilization. 4. For each experimental task, either standing or balancing the equivalent body, sway was recorded while posture was unperturbed. Root mean square values of sway amplitude and power spectra were used to compare conditions. 5. Every subject could balance the equivalent body in a stable way when the eyes were closed, and when the feet were anaesthetized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869256 TI - Ca2+ load of guinea-pig ventricular myocytes determines efficacy of brief Ca2+ currents as trigger for Ca2+ release. AB - 1. In guinea-pig ventricular cells, the concentration of ionized cytosolic calcium ([Ca2+]o) was estimated from the fluorescence of 100 microM K5-indo-1. At 36 degrees C and 2 mM [Ca2+]o, the Ca2+ load of the cells was varied by 1 Hz trains of conditioning clamp pulses to -30 mV (low Ca2+ load), 0 mV (intermediate Ca2+ load) and paired pulses (high Ca2+ load). After seven pulses potentiation was steady and short test pulses to 0 mV were tested for their efficacy in triggering [Ca2+]c transients. The influx of trigger Ca2+ was graded by varying the test-pulse duration between 1 and 180 ms. 2. After a 3 min rest period, [Ca2+]c was 100 +/- 20 nM (mean +/- S.E.M.) and 2 ms test pulses were unable to induce [Ca2+]c transients. Test pulses of 2 ms duration, however, induced [Ca2+]c transients after potentiation with single or paired pulses. 3. At high cellular Ca2+ load, the amplitude of the [Ca2+]c transients (delta[Ca2+]c) gradually increased with pulse durations up to 8 ms. Pulse durations between 8 and 160 ms, however, did not further increase delta[Ca2+]c as if the largest part of the [Ca2+]c transient was due to regenerative contribution of Ca(2+)-induced Ca2+ release. 4. Pulses of 160 ms duration induced 'saturating' responses whose amplitudes delta[Ca2+]c, t = infinity decreased from 938 +/- 120 nM at high Ca2+ load, to 610 +/- 90 and 350 +/- 120 nM at intermediate and low Ca2+ loads, respectively. 5. Delta[Ca2+]c was more sensitive to the duration of Ca2+ influx at low or intermediate Ca2+ loads than at high Ca2+ load. When delta[Ca2+]c was plotted against the test-pulse duration, 50% of delta[Ca2+]c, t = infinity was found to be at 9 +/- 2 ms (low), 4.6 +/- 1 ms (intermediate) or 1.8 +/- 0.5 ms pulses (high Ca2+ load). Correspondingly, the efficacy of 2 ms test pulses in triggering [Ca2+]c transients increased with the Ca2+ load. 6. At high Ca2+ load, [Ca2+]c peaked nearly independently of pulse duration at 19 +/- 3 ms. At intermediate or low Ca2+ load, time to peak increased with pulse duration. 7. The results confirm the theory that sarcoplasmic reticulum (SR) Ca2+ release contributes an amount to the [Ca2+]c transient that increases with the cellular Ca2+ load. The results are compatible with the hypothesis that SR Ca2+ release can be activated by both Ca2+ influx and by SR Ca2+ release and that the latter mechanism constitutes a positive feedback, the amplification of which increases with the amount of releasable Ca2+. PMID- 7869257 TI - Gradation of Ca(2+)-induced Ca2+ release by voltage-clamp pulse duration in potentiated guinea-pig ventricular myocytes. AB - 1. This study tests the hypothesis that whole-cell cardiac SR Ca2+ release is graded by recruitment of independent 'release units'. Structurally, an individual release unit may comprise ca four sarcolemmal L-type Ca2+ channels, adjacent ryanodine-sensitive sarcoplasmic reticulum (SR) Ca2+ release channels and the junctional gap between them. After depolarization, the first opening of a single L-type Ca2+ channel of the unit provides sufficient Ca2+ influx to increase local [Ca2+] beyond the threshold activating Ca(2+)-induced Ca2+ release (CICR), which amplifies local [Ca2+] until all release channels of the unit are active. This all-or-none activation does not spread to other release units. Gradation of whole cell Ca2+ release is predicted to correlate with the cumulative probability density distribution of first latency of L-type Ca2+ channels or the activation time course of the calcium current, ICa. 2. Guinea-pig ventricular myocytes were potentiated by paired voltage-clamp pulses (1 Hz, 2 mM [Ca2+]o, 40 microM K5-indo 1, 36 degrees C). When the cellular Ca2+ load was at a steady high level, cytosolic calcium concentration ([Ca2+]c) transients were measured in response to test pulses of varied pulse duration (PD, 1-180 ms) and amplitude (-20, 0, 20 and 50 mV). The maximal rate of rise (RRmax) of the [Ca2+]c transient was used as an indicator for SR Ca2+ release. 3. Fast [Ca2+]c transients due to 4 ms pulses to 0 or 50 mV were blocked by 1 mM cadmium suggesting that these Ca2+ release signals are triggered by Ca2+ influx through L-type Ca2+ channels and not by Ca2+ influx through Na(+)-Ca2+ exchange. 4. RRmax increased with longer PD along the sigmoidal curve [1-exp(-PD/tau)]kappa(exponent k: 2 < k < 3). The time constant, tau, resembled the activation time constant of whole-cell ICa (Cs(+)-dialysed cells). A PD longer than a limiting duration did not modify RRmax. That is, inactivation of ICa was not reflected in the duration dependence. 5. Single L type Ca2+ channels (cell-attached patches, 36 degrees C, -20 mV, 3.6 mM CaCl2 and 1 microM Bay K 8644 in patch pipette) opened with a waiting time the cumulative probability distribution of which resembled the duration dependence of RRmax, suggesting that the first opening of L-type Ca2+ channels determines whether the corresponding release unit contributes to the [Ca2+]c transient activated during a short voltage-clamp pulse. 6. The time constant, tau, of the duration dependence was shorter at positive than at negative potentials.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7869258 TI - Stretch effects on whole-cell currents of guinea-pig urinary bladder myocytes. AB - 1. By means of two patch-pipettes, isolated urinary bladder myocytes were longitudinally stretched up to 20% beyond slack length (delta L = 20%). 2. Experiments were conducted using both voltage and current clamp configurations. In current clamped cells at 23 degrees C, delta L depolarized the membrane from 50 to ca -15 mV, the amplitude of depolarization increasing with the extent of delta L. At 36 degrees C, delta L induced action potentials or increased the frequency of spontaneous action potentials. 3. In voltage clamped cells at a holding potential of -50 mV, stretch induced an inward current (Iin) and increased the input conductance. Both effects increased with delta L. They were blocked by 40 microM gadolinium, suggesting stretch activation of non-selective cation channels (SACs) as the underlying mechanism. 4. Stretch-induced difference currents rectified outwardly and reversed at a reversal potential (Erev) of -28 +/- 10 mV. Twenty millimolar [TEA]o suppressed the rectification and shifted Erev to 0 +/- 1 mV. The result suggests that stretch can activate not only SACs but also TEA-sensitive K+ channels. 5. Stretch changed the net current due to clamp steps to 0 mV as though it increased the potassium current (IK) and reduced the calcium current (ICa). While 20 mM intracellular BAPTA did not modify the stretch induced whole-cell inward current (Iin) at -50 mV, it suppressed the stretch effects on IK and ICa as if these effects were mediated by an increase in the subsarcolemmal Ca2+ concentration. 6. The results support the hypothesis that longitudinal stretch can activate SACs and Ca2+ influx through them. In non clamped cells, stretch can also modulate Ca2+ influx through L-type Ca2+ channels via changes in membrane potential. PMID- 7869259 TI - Dual modulation of unitary L-type Ca2+ channel currents by [Ca2+]i in fura-2 loaded guinea-pig ventricular myocytes. AB - 1. Single-channel studies were performed to clarify how tonic changes in intracellular Ca2+ concentrations ([Ca2+]i) modulate cardiac L-type Ca2+ channels. Currents were recorded from fura-2-loaded guinea-pig ventricular myocytes in the cell-attached configuration. Fura-2 fluorescence signals were recorded simultaneously during pulses to elicit channel activity. 2. The myocyte [Ca2+]i was altered through changes in bath Ca2+ concentration during K+ depolarization. When [Ca2+]i exceeded approximately 2 times the resting level (estimated [Ca2+]i around 180-400 nM), the activity of Ca2+ channels was reversibly potentiated without changes in unitary current amplitudes. 3. Increased channel open probability during Ca(2+)-dependent potentiation resulted from increased availability and increased open probability during non-blank sweeps. Closed time analysis revealed a distribution best fitted with two exponentials. Increased [Ca2+]i reduced the longer time constant, but had no effect on the shorter time constant. The open time constant was unchanged in most cases. Current records occasionally included sweeps with long openings (approximately 10 ms or more), whose appearance increased during potentiation. 4. When [Ca2+]i was increased after cAMP-dependent upregulation of Ca2+ channels, the change in channel activity was diminished. Similar results were observed when Ca(2+)-dependent potentiation was examined in myocytes exposed to a membrane permeant protein kinase inhibitor, H-89. This suggests that channel phosphorylation may be responsible for Ca(2+)-dependent potentiation. 5. When [Ca2+]i was further increased, but remained below the threshold for contraction (estimated [Ca2+]i above 600 nM), Ca2+ channel activity was suppressed. 6. Our results demonstrate directly at the single-channel level that [Ca2+]i modulates the activity of cardiac L-type Ca2+ channels, enhancing it with modest [Ca2+]i increases and decreasing it with greater [Ca2+]i increases. PMID- 7869260 TI - Regenerative and non-regenerative calcium transients in hamster eggs triggered by inositol 1,4,5-trisphosphate. AB - 1. Inositol 1,4,5-trisphosphate (InsP3) injected into unfertilized golden hamster eggs elicits a hyperpolarizing response (HR) that is due to stimulation of calcium-activated potassium channels in the egg plasma membrane. 2. A single injection of InsP3 gave a single HR above a threshold value of 0.3 nM. At 5 nM and above, InsP3 induced HRs with no detectable latency. At concentrations between these two values a latency was observed. The amplitude of the HR was independent of InsP3 concentration. 3. A second HR could be elicited by injection of InsP3, but five times more InsP3 was required to trigger a second HR, and 10 100 times more to give an HR of similar magnitude to the first, and there was no latency. 4. The increase in [Ca2+]i in response to an initial injection of 1 nM InsP3 could be resolved into two distinct components: a slow, early rise immediately after InsP3 injection (phase I) followed by a larger and more rapid increase (phase II). The initiation of an HR coincided with the second component of the [Ca2+]i increase. 5. Further injection of InsP3 resulted only in slow, smaller increases in [Ca2+]i that resembled phase I and often did not cause an HR. Phase II appeared to be absent. However, 100-fold greater InsP3 concentrations gave slow, larger Ca2+ transients (and HRs) with no detectable latency. 6. If large amounts of InsP3 were allowed to leak into the eggs constantly from a pipette, repetitive calcium transients were seen. Unlike the sustained repetitive responses seen at fertilization, they were often smaller than the initial transient and less well sustained. However, a subsequent transient could still be elicited on injection of very large concentrations of InsP3. 7. InsP3 can induce regenerative, all-or-none [Ca2+]i increase (CICR) in hamster eggs, often with a long latency, as well as non-regenerative increases. InsP3 injections desensitize CICR and cannot mimic all the features of Ca2+ signalling at fertilization in the hamster egg, in particular, the sensitization of CICR caused by the sperm. PMID- 7869261 TI - Selective potentiation of a novel calcium channel in rat hippocampal neurones. AB - 1. Calcium channel activity in cultured embryonic hippocampal neurones was studied with the cell-attached configuration of the patch clamp technique. Single channel recordings revealed the presence of a novel kind of calcium channel activity characterized by marked bursts of re-openings following voltage pulses to +20 mV from a holding potential of -40 mV. 2. The re-openings were greatly prolonged by the dihydropyridine (DHP) agonist (+)-(S)-202-791, thus ruling out the possibility that they arose from T-, N- or P-type channels. Furthermore, the novel gating pattern could be readily distinguished from that of the L-type channel which showed only conventional tail currents. 3. Since the novel gating pattern was stable over many minutes, we provisionally referred to it as a novel kind of calcium channel that showed voltage-dependent potentiation (Lp channel) to distinguish it from the 'standard' L-type channel (Ls channel). 4. Lp channels could also be distinguished from Ls channels on the basis of slope conductance (24.3 vs. 26.9 pS for Lp and Ls, respectively) and mean DHP-induced long open time (2.7 vs 11 ms at +20 mV for Lp and Ls, respectively). 5. Voltage-dependent potentiation of Lp channel activity was studied using a dual-pulse protocol. When preceded by conditioning prepulses, Lp responses to test pulses were greatly increased. Ls- and N-type calcium channels showed no such enhancement of their activity. 6. Long-duration recordings revealed no clear evidence for transitions from Ls to Lp gating (or vice versa), suggesting that Ls and Lp activities arose from different kinds of calcium channels or that Lp gating is an unusually long lived mode of Ls channel gating. PMID- 7869262 TI - Enhancement by prostaglandin E2 of bradykinin activation of embryonic rat sensory neurones. AB - 1. The capacity of prostaglandin E2 (PGE2) to enhance the excitatory response elicited by bradykinin in embryonic rat sensory neurones grown in culture was investigated using the whole-cell patch-clamp recording technique. 2. The focal application of bradykinin (BK) produced a small concentration-dependent depolarization that was associated with an inward current and was described by a ligand-binding isotherm having an EC50 of 230 nM. Typically the depolarization was accompanied by action potentials (APs). 3. After pretreatment with 1 microM PGE2 for 10 min, the number of APs elicited by 100 nM BK was increased by about 3 fold. However, PGE2 had no effect on the amplitude of either the BK-elicited depolarization or inward current. The addition of 1 or 10 microM PGE2 had no effect on the resting membrane potential. 4. In all neurones exhibiting PGE2 enhanced excitability, there was a decrease in the amount of injected current necessary to elicit an AP. 5. The enhanced excitability was not due to repeated exposure to BK since neither the amplitude of the BK-evoked depolarization nor the number of APs was altered by the application of BK at 2 min intervals over a period of 30 min. 6. These results are consistent with the notion that PGE2 acts directly on sensory neurones to enhance the response to chemical excitatory agents, like BK, by lowering the AP firing threshold. The PGE2-mediated sensitization does not result from an alteration of the resting potential or modulation of the neuronal response to the chemical agonist. PMID- 7869264 TI - The quantal size at retinogeniculate synapses determined from spontaneous and evoked EPSCs in guinea-pig thalamic slices. AB - 1. To determine the quantal size at retinogeniculate synapses, spontaneous and evoked excitatory postsynaptic currents (EPSCs) were recorded in twelve neurones of the dorsal lateral geniculate nucleus in guinea-pig thalamic slices using the whole-cell patch-clamp technique. We limited our study to the fast non-N-methyl-D aspartate (NMDA) component of the EPSCs by adding the NMDA receptor antagonist DL 2-amino-5-phosphonovaleric acid to the perfusion medium. 2. Spontaneous EPSCs occurred at a frequency between 0.5 and 6.6 Hz (mean 2.5 Hz). The modal value of the peak conductance change of spontaneous excitatory events varied between cells from 102 to 179 pS. 3. EPSCs were evoked by electrical stimulation in the optic tract. The peak conductance change of EPSCs evoked by stimulation of a putative single input fibre ranged from 0.6 to 3.4 nS (mean 1.7 nS). 4. To resolve the quantal components of evoked EPSCs the external Ca2+ concentration was reduced and the external Mg2+ concentration increased for four cells. In this condition failures occurred and the amplitude histograms were multimodal with approximately equidistant peaks. 5. These multimodal histograms could be fitted by a sum of Gaussian functions with mean values corresponding to integer multiples of the modal value of the spontaneous EPSCs for the same cell. Thus, the quantal size of evoked EPSCs was the same as the modal value of spontaneous EPSCs. The mean of the apparent quantal conductance change was 138 pS. The estimated number of quanta released by stimulating a putative single input fibre in the control condition ranged from 4 to 27 (mean 13).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869263 TI - Transient expression of a novel type of GABA response in rat CA3 hippocampal neurones during development. AB - 1. Intracellular recordings were used to study the effects of gamma-aminobutyric acid (GABA) on rat CA3 hippocampal neurones during the first two weeks of postnatal life. 2. In the presence of tetrodotoxin (TTX, 1 microM), from postnatal day 0 (P0) to P12 both associated with an increase in input conductance whereas baclofen (30-100 microM) produced a membrane hyperpolarization. 3. Bicuculline (50 microM) reduced the effects of GABA and abolished the response to isoguvacine without affecting the response to baclofen. 4. This novel bicuculline insensitive GABA response was chloride dependent and was blocked by picrotoxin (10-100 microM) in an uncompetitive way. In bicuculline and picrotoxin, a GABAB mediated hyperpolarization appeared. 5. Towards the end of the second postnatal week, bicuculline blocked the GABA-induced depolarization and revealed a small hyperpolarizing response which was blocked by the GABAB antagonist CGP 35348 (0.5 1 mM). 6. It is suggested that, during development, the GABA response was mediated through the conventional GABAA and GABAB receptors as well as a new bicuculline-baclofen-insensitive type of receptor. PMID- 7869265 TI - Muscarinic amplification of fast excitation in hilar neurones and inhibition in granule cells in the guinea-pig hippocampus. AB - 1. Effects of the cholinergic agonist, carbachol (CCh), or the acetylcholinesterase inhibitor, eserine, on presumed inhibitory hilar neurones and on inhibition in granule cells were studied by intracellular recording in guinea-pig hippocampal slices. 2. CCh (1-5 microM) strongly enhanced the discharge activity of hilar neurones and spontaneous and evoked IPSPs in granule cells. 3. Eserine, in an atropine-sensitive manner, increased the excitability of hilar neurones through effects on membrane properties and on excitatory synaptic barrage. EPSPs readily triggered long-duration burst discharges. In granule cells, the amplitudes of evoked GABAA and GABAB receptor-mediated IPSPs were enhanced. 4. In the presence of eserine and antagonists for glutamatergic and GABAergic synaptic transmission, train stimulation evoked atropine-sensitive slow EPSPs. In contrast to those in granule cells, slow EPSPs in hilar neurones were invariably preceded by a strong burst-after-hyperpolarization. 5. We suggest that acetylcholine, released from septo-hippocampal fibres, amplifies fast synaptic excitation of inhibitory hilar neurones and inhibition of granule cells. In the dentate area, muscarinic receptor-mediated effects are faster than anticipated from the time course of the slow EPSP. PMID- 7869266 TI - Desynchronization of epileptiform activity by extracellular current pulses in rat hippocampal slices. AB - 1. A single cathodic current pulse applied in the somatic CA1 region of the hippocampus was found to induce a large decrease in the amplitude of the population spike. 2. Intracellular recordings showed intense cellular firing suggesting the amplitude decrease could not be attributed to a decrease in neuronal firing. 3. Simultaneous intracellular and extracellular potentials were recorded to analyse the synchronization of neuronal firing in the CA1 region. Action potentials were synchronized with the first population spike but this synchronization decreased with subsequent spikes. Histograms of the phase of the action potentials displayed a normal distribution. 4. Histograms of the phases of the action potentials following the application of the 'singular stimulus' (one producing a singular response) revealed a uniform distribution of the phases suggesting that the neuronal population was desynchronized. 5. This desynchronization effect of the singular stimulus was verified by double intracellular recordings. The simultaneous firing of two neurons could be desynchronized by the application of the singular stimulus. 6. These findings indicate that it is possible to desynchronize a neuronal pool with the application of a single current pulse. In addition, the results show that it is possible for a neuronal population to fire a large number of action potentials with no resulting evoked potentials in the extracellular space. PMID- 7869267 TI - The separation of exocytosis from endocytosis in rat melanotroph membrane capacitance records. AB - 1. Using the patch-clamp technique, we have monitored the secretory activity of single rat melanotrophs. Changes in membrane capacitance (Cm) were measured to detect small discrete femtofarad steps. These are believed to be due to interactions between single secretory organelles (granules) and plasmalemma. 2. A new approach was introduced to measure the amplitude of discrete steps in Cm. Records of Cm were converted into time derivatives, where discrete steps appeared as transients. A transient due to a 2 fF discrete step in Cm was easily distinguished from random noise, since the probability of such a transient being due to random noise was less than 0.01. To distinguish apparent steps from noise the computer-based analysis employed a threshold of 3 times the standard deviation of the noise time derivative (dCm/dt). A phase diagram was created by plotting dCm/dt versus Cm, from which the magnitude and direction of transients were determined. Transients due to 2 fF steps (equivalent to a signal-to-noise ratio of 1) were detected with a reliability of 100%, whereas steps of 1 fF were detected with a reliability of more than 60%. The amplitude of false steps detected by the program was less than 1 fF, and the frequency of false detections of 0.075 S-1 was equal for exocytotic and endocytotic events. 3. Electron microscopy was used to measure secretory organelle size and an immunogold technique was used to label the electron micrographs with an anti adrenocorticotrophin (ACTH) antibody. Secretory organelles in cultured and non cultured cells were of similar diameter. All sizes of secretory granules appear to contain ACTH, since secretory organelles of similar diameter stained positively with the anti-ACTH antibodies. 4. Small discrete steps in Cm, recorded with the whole-cell configuration and loosely buffered cytosolic calcium, were similar to the estimated Cm of secretory organelles from morphological data. Thus, measured discrete steps in Cm reflect interactions between single organelle size and plasma membrane. Exocytotic and endocytotic steps were found to be of similar size. 5. To separate exocytosis from endocytosis in Cm records, we assumed that the rates of exocytosis and endocytosis were related to the respective frequencies of discrete steps in Cm. A relationship between the frequency of exocytotic, but not endocytotic events, and the rate of change in Cm was observed. Thus, under our experimental conditions, an increase in Cm could be explained by an increased rate of exocytosis in rat melanotrophs. PMID- 7869268 TI - Block of stretch-activated atrial natriuretic peptide secretion by gadolinium in isolated rat atrium. AB - 1. Isolated superfused rat atrial preparations were used to study the mechanism of stretch-induced atrial natriuretic peptide (ANP) secretion. The stretch of the atrial myocytes was induced by raising the intra-atrial pressure. The secretion rates were analysed by measuring ANP concentrations from the superfusate fractions by radioimmunoassay. 2. The effect of gadolinium, a blocker of stretch activated ion channels, on stretch-induced and basal ANP secretion was investigated by superfusing the atrial preparation with 5, 20 or 80 microM GdCl3. Gadolinium decreased stretch-induced ANP secretion in a dose-dependent manner, but did not affect basal secretion. 3. Because high concentrations of gadolinium may block voltage-gated calcium channels, we tested whether the selective blockers of L-type (diltiazem) and T-type (NiCl2) calcium channels affect the stretch-stimulated ANP release. Neither diltiazem at 3 microM nor NiCl2 at 50 microM affected stretch-induced ANP release in paced atrial preparation. 4. Gadolinium, but not diltiazem, also inhibited stretch-stimulated ANP secretion in non-paced, quiescent atria. 5. The findings that ANP release is inhibited by Gd3+, but not by diltiazem or NiCl2, and that the stretch-induced secretion in quiescent atria is also inhibited by Gd3+, suggest that stretch-activated ion channels are involved in the regulation of stretch-induced ANP release. PMID- 7869269 TI - Neuronal regulation of cochlear blood flow in the guinea-pig. AB - 1. Previous studies have shown that electrical stimulation (ES) of the guinea-pig cochlea causes a neurally mediated increase in cochlear blood flow (CBF). It is known that the centrifugal neuronal input to the cochlea comes through the perivascular sympathetic plexus from the cervical sympathetic chain and along the vestibular nerve (VN) from the periolivary area of the brainstem. Both of these neuronal systems are distributed topographically in the cochlea. 2. In order to study the neural origins of ES-evoked CBF increase, laser Doppler flowmetry was used to test the following hypotheses. (a) The response is regional, that is, limited to the area of the cochlea stimulated. To test this we performed differential ES of the cochlear turns. CBF was measured from either the third or the first turn. (b) The response is mediated via autonomic receptors within the cochlea. To study this, we applied atropine, succinylcholine and idazoxan locally to the cochlea. (c) The response is influenced by neuronal input via the sympathetic cervical chain (SC) and components of the VN. We stimulated and sectioned the SC, and sectioned the VN, to test this hypothesis. 3. We observed that the CBF response was topographically restricted to the stimulated region. Locally applied muscarinic or nicotinic antagonists (atropine and succinylcholine respectively) did not affect the response. However, local idazoxan (an alpha 2 blocker) eliminated the response. Locally applied adrenaline and SC stimulation modified the dynamic range of the response. SC sectioning enhanced the responsiveness of the cochlear vasculature to ES. The VN section caused a temporary decrease in CBF and elimination of the ES-evoked CBF response. 4. We conclude that the release of dilating agents is topographical with respect to ES current flow, the ES-evoked CBF increase is peripherally mediated via alpha 2 receptors, and the response is influenced by input via the SC. The elimination of the response by VN sectioning proximal to the brainstem indicated that fibres of the VN mediate the CBF increase during direct cochlear ES. The data suggest that these fibres may be the efferent limb of a neural loop involved with the regulation of CBF. Such a system could provide a mechanism for the rapid increase in CBF with organ stress. PMID- 7869270 TI - Vagal influence on the motility of the feline jejunum. AB - 1. The effects of electrical stimulation of the peripheral end of the cervical vagal nerve on jejunal motility were investigated in anaesthetized cats, pretreated with guanethidine, with sectioned splanchnic nerves and ligated adrenal vessels. Motility was monitored as volume changes of an intraluminal balloon. 2. Vagal stimulation elicited frequency-dependent hypermotility with a short latency. Relaxatory events were also observed, which could indicate the presence of a non-adrenergic inhibitory pathway. 3. After atropine treatment, contractions and relaxations could still be elicited. The former were compared to cholinergic contractions and showed a lower maximal amplitude and a longer latency to onset. Moreover, they were antagonized by 80-100% by the opioid receptor antagonist, naloxone. 4. Vagal stimulation after hemicholinium, given in order to deplete the preganglionic acetylcholine content, elicited naloxone sensitive contractions. This suggests that a subpopulation of the vagal preganglionic fibres is non-cholinergic. 5. Isolation of the balloon-containing segment did not qualitatively alter the responses, indicating that the vagal fibres reach the small intestine via the paravascular mesenteric nerves. 6. It is concluded that cholinergic and non-adrenergic, non-cholinergic (NANC) contractions, as well as relaxations, could be elicited by efferent vagal stimulation. The NANC contractions seem to result from the activation of opioid receptors causing disinhibition of a tonic neurogenic restraint on the gut muscle. PMID- 7869271 TI - Medullary loci critical for expression of gasping in adult rats. AB - 1. Our purpose was to define whether a region of medulla could be identified that is critical for the expression of gasping. 2. Decerebrate, vagotomized, paralysed and ventilated adult rats were used. The pattern of phrenic activity was reversibly altered from eupnoea to gasping by exposure to hypoxia or anoxia. 3. Gasping was irreversibly eliminated following unilateral electrolytic lesions of the lateral tegmental field of the medulla. The eupnoeic rhythm continued after these lesions. 4. Injections of kainic acid into the lateral tegmental field also eliminated gasping. Phrenic activity in eupnoea was not altered. 5. Lesions outside the lateral tegmental field caused marked changes in the eupnoeic rhythm, including expiratory apnoea. Upon exposure to hypoxia or anoxia, gasping was still induced. 6. This region for the neurogenesis of gasping in rats is identical to the region that serves a comparable function in cats. Moreover, it overlaps with the 'pre-Botzinger' complex which has been described for the in vitro brainstem preparation of the neonatal rat. Our results raise doubts that this complex plays a role in the neurogenesis of eupnoea. PMID- 7869273 TI - Interdependence of respiratory and cardiovascular changes induced by systemic hypoxia in the rat: the roles of adenosine. AB - 1. In ten spontaneously breathing, Saffan-anaesthetized rats (group I), respiratory and cardiovascular responses evoked by 10 min periods of hypoxia (arterial partial pressure of O2, Pa,O2, 33 mmHg) were recorded before and after the administration of the adenosine receptor antagonist 8-phenyltheophylline (8 PT, 10 mg kg-1 i.v.). Similar experiments were performed on nine constantly ventilated rats (group II; Pa,O2, 29 mmHg) with arterial partial pressure of CO2 (Pa,CO2) held constant. 2. In group I, hypoxia induced an initial increase and a secondary fall in ventilation (VE) with an accompanying secondary fall in heart rate (HR), arterial pressure (ABP) fell and cerebral vascular conductance (CVC) increased progressively. Cerebral blood flow (CBF) tended to fall with time during hypoxia. 8-PT abolished the secondary falls in VE and HR and reduced the fall in ABP and increase in CVC, while CBF was better maintained. 3. In group II, hypoxia induced a similar cardiovascular response to that in group I, but at the 1st minute of hypoxia, the HR was lower and the increase in CVC was greater. 8-PT did not affect the hypoxia-induced changes in HR, ABP, CVC or CBF. 4. These results indicate specific ways in which the ventilatory and cardiovascular responses induced by hypoxia in the spontaneously breathing rat are interdependent. They also indicate that the influences of 8-PT on the cardiovascular changes induced by hypoxia during spontaneous ventilation are mainly a consequence of its ability to block the centrally mediated contribution of adenosine to the secondary fall in ventilation. PMID- 7869274 TI - Proceedings of the scientific meeting of the Physiological Society. Aberdeen, 14 16 September 1994. Abstracts. PMID- 7869272 TI - Evidence that antidromically stimulated vagal afferents activate inhibitory neurones innervating guinea-pig trachealis. AB - 1. We recently described a capsaicin-sensitive vagal pathway mediating non adrenergic, non-cholinergic (NANC) relaxations of an isolated, innervated rostral guinea-pig tracheal preparation. These afferent fibres are carried by the superior laryngeal nerves and relaxations elicited by their activation are insensitive to autonomic ganglion blockers such as hexamethonium. In the present study this vagal relaxant pathway was further characterized. 2. Relaxations of the trachealis elicited by electrical stimulation of capsaicin-sensitive vagal afferents were mimicked by bath application of capsaicin. Relaxations elicited by both methods were abolished when the tissue between the trachea and the adjacent oesophagus was disrupted. Indeed, separating the trachea from the oesophagus uncovered a contractile effect of capsaicin administration on the trachealis. 3. Capsaicin-induced, oesophagus-dependent relaxations of the trachealis were blocked by pretreatment with the fast sodium channel blocker tetrodotoxin (TTX). By contrast, capsaicin-induced contractions of the trachealis (obtained in the absence of the oesophagus) were unaffected by tetrodotoxin. 4. Substance P, neurokinin A (NKA) and neurokinin B (NKB) also elicited NANC relaxations of precontracted trachealis that were abolished by separating the trachea from the oesophagus or by TTX pretreatment. Like capsaicin, the tachykinins elicited only contractions of the trachealis following TTX pretreatment or separation of the trachea from the adjacent oesophagus. 5. Relaxations elicited by stimulation of the capsaicin-sensitive nerves were unaffected by a concentration of the tachykinin NK2 receptor-selective antagonist, SR 48968, that is selective for NK2 receptor blockade and were not mimicked by the NK2 receptor-selective agonist [beta-Ala8]-NKA(4-10). This suggests that NK2 receptors are not responsible for these relaxations. By contrast, the NK3 receptor-selective agonist, senktide analogue, and the NK1 receptor-selective agonist, acetyl-[Arg6, Sar9, Met (O2)11] SP(6-11), elicited oesophagus-dependent relaxations of the trachealis that were abolished by oesophagus removal. Furthermore, pretreatment with the NK1-selective antagonists, CP 96345 and CP 99994, or pretreatment with a concentration of SR 48968 that also blocks NK3 receptors, markedly attenuated relaxations elicited by stimulation of the capsaicin-sensitive vagal pathways. 6. The data are consistent with the hypothesis that relaxations elicited by stimulation of capsaicin sensitive vagal afferents involve tachykinin-mediated activation of peripheral NANC inhibitory neurones that are in some way associated with the oesophagus. The data also indicate that airway smooth muscle tone might be regulated by peripheral reflexes initiated by activation of capsaicin-sensitive afferent fibres. PMID- 7869275 TI - Rehabilitation research and development progress reports 1992-1993. PMID- 7869276 TI - Balance and stabilization capability of paraplegic wheelchair athletes. AB - The orientation of paraplegic athletes toward adapted sport activities required good knowledge of their functional characteristics. Wheelchair locomotion, especially for highly dynamic situations, poses the problem of trunk equilibrium management and head stabilization. The study aimed at designing a quantitative method to assess the ability of paraplegics to obtain trunk balance under dynamic stresses, and to analyze the various balance strategies, according to the spinal lesion level of the subjects. High (HPA) and low (LPA) paraplegic athletes were subjected to four series of antero-posterior stresses of increasing intensity, generated by an oscillating platform. By means of a computerized video-based movement analyzer, acceleration in the saggittal plane was measured at four different spinal level and, for each one, a damping factor was determined. This factor, computed at the head level, appeared to be representative of the subjects' ability to maintain balance. We attempted to differentiate balance strategies in the LPA and HPA groups through analysis of the relative contributions to damping of the thoracic and cervical spinal segments. The first results show an increasing tendency of neck reflex stiffening according to the neurological level. PMID- 7869277 TI - A survey of marginal wheelchair users. AB - Significant numbers of wheelchair users experience difficulties with propulsion due to impaired upper limb function (termed marginal users for this study). A survey of wheelchair users in Tayside, Scotland, was carried out to identify and describe the marginal user population and their propulsion difficulties. Subjects for the survey were identified from the records of National Health Service wheelchair users at Dundee Limb Fitting Centre. Subjects were interviewed at home about their wheelchair-propelling experiences. Survey results indicated that marginal users represent approximately 15% of the occupant-propelled wheelchair population. The average age of the marginal users surveyed was 48 years and the modal diagnosis was multiple sclerosis. Fifty-nine percent of the marginal users questioned felt that their wheelchairs were not adequate for their requirements. PMID- 7869278 TI - Distributed random electrical neuromuscular stimulation: effects of the inter stimulus interval statistics on the EMG spectrum and frequency parameters. AB - An electrophysiological approach was used to study a distributed random electrical neuromuscular stimulation (ENMS) scheme in which a probability density is assigned to the inter-stimulus intervals (ISI) of the stimuli. One of the objectives of using ENMS techniques in the study of skeletal muscles is to obtain information about the electrical, physiological, and mechanical properties of muscles in a near-physiological situation under a well-controlled experimental design in which problems related to the uncertainty of firing patterns of the central nervous system and physiological interference are avoided. In particular, ISI with a Gaussian density were varied in mean rate, standard deviation (SD), and coefficient of variation. The influence of varying ISI, and the interaction of the ISI statistics with compound motor unit action potentials (CMUAP) on EMG power spectra and their frequency parameters, was assessed theoretically using a mathematical model which is similar to that of EMG signal generation in the electrophysiological case. In order to quantify the effects of ISI statistics on the EMG spectrum, the median frequency was calculated as a function of stimulation rate using analytical expressions for various values of the coefficients of a Gaussian ISI variation. The results obtained suggest that 1) the interaction between ISI statistics and the shape of the CMUAP plays a major role in determining the EMG spectrum; 2) the median frequencies (MF) determined from EMG spectra tend to increase with increasing mean rates of stimulation for a given CMUAP. The rate of increase of the MF depends on the coefficient of the ISI variation; 3) the EMG spectra of random electrically stimulated muscle show peaks at the mean rate of stimulation, and multiples of it, when the coefficient of variation of ISI is small. These peaks decrease in magnitude with increasing coefficients of variation of ISI; and, 4) a variation in the ISI should be introduced in the ENMS, when a reproduction of 'normal' EMG spectra is needed. These results are consistent with those reported for voluntary contraction of skeletal muscles. PMID- 7869279 TI - Initial clinical evaluation of a wheelchair ergometer for diagnostic exercise testing: a technical note. AB - The purpose of this initial study was to evaluate a new wheelchair ergometer (WCE) and exercise test protocol for the detection of coronary artery disease in men with lower limb disabilities. Forty-nine patients (63 +/- 9 yr) completed WCE tests without complications. Peak heart rate was 84 +/- 15% (mean +/- SD) of age predicted maximum and peak double product was 223 +/- 62 x 10(2). The specified target heart rate (> or = 80% age-predicted maximal) or a positive result was achieved in 76% of tests. Fourteen tests were rated positive, 21 as negative and 14 as nondiagnostic for exercise-induced ischemia. In 18 patients who underwent coronary angiography, the predictive value was 100% (10/10) for a positive, and 50% (2/4) for a negative WCE test result. These results suggest that WCE is a viable initial diagnostic option for some persons who cannot adequately perform treadmill or cycle ergometry exercise. PMID- 7869280 TI - The Southampton Hand: an intelligent myoelectric prosthesis. AB - The form of the control and structure of the mechanism of an artificial hand are important factors which tend to dictate the prosthesis' level of use. Conventional prostheses are simple devices with limited functional range and a control format that requires high levels of user concentration for successful operation. The Southampton Adaptive Manipulation Scheme (SAMS) is a hierarchical control format that allows a larger number of independent motions to be controlled while requiring a smaller degree of user input. The SAMS control has been applied to different hand mechanisms, both custom-made and modified commercial systems. Their application with users shows them to have a performance on a par with, or superior to, other conventional devices. The form of prosthesis control is reviewed and the development of, and clinical experiments with, the Southampton Hand are outlined. PMID- 7869281 TI - Toward classification of dysphagic patients using biomechanical measurements. AB - Identification of a patient at risk of aspiration is a major problem in the rehabilitation of the dysphagic patient. The present methods of diagnosis are based on clinical evaluation or videofluorography or fiberoptic endoscopic examination of swallowing (FEES). Recently, we developed biomechanical techniques for noninvasive quantitative assessment of the dysphagic patient. The purpose of the present investigation was to assess the clinical validity of the technique. In a double-blind study, both biomechanical test results and videofluorography (including bedside evaluation) results were used to independently classify the patients into four categories of risk for aspiration. Of the 36 patients studied, there was complete agreement between the biomechanical and clinical classifications in 21 patients. In 11 patients, the biomechanical technique overestimated the risk by one category, and underestimated the risk by one category in four patients. The biomechanical technique presents a useful tool for continued patient assessment; however, further studies are needed. PMID- 7869282 TI - Voice output reader for displays on video cassette recorders and other domestic products. AB - The increasing use of electronic displays in domestic products can pose great problems for blind people wishing to use microwave ovens, video cassette recorders, hi-fi systems, etc. One method of trying to solve these problems is to provide a handheld "display reader" that can translate the alphanumeric and symbolic information presented on the display into speech. A prototype system has been developed and evaluated. User requirements for this device and the problems of the image sensor, the image processing method, and the user interaction with the system are also discussed. PMID- 7869283 TI - Clinical and laboratory study of amputation surgery and rehabilitation. PMID- 7869284 TI - Who is at risk of limb loss and what to do about it? AB - Lower limb amputations were performed on over 105,000 individuals in United States short-stay hospitals between 1989 and 1992. Additional amputations were performed in VA, military, Indian Health, and charitable orthopaedic hospitals. Half of all lower extremity amputations occurred in individuals with diabetes. When the causal chain leading to diabetic amputations was examined in 80 consecutive patients at the VA Medical Center, Seattle, WA, 23 unique pathways were identified. Multiple pathway components were identified for 96% of patients, while in 4% a single ischemic pathway was sufficient in itself to require amputation. The majority of the scenarios leading to amputation began when patients with absent peripheral sensation sustained a pivotal event that initiated the causal chain to amputation. In nearly half the patients, this event was foot-wear-related. The pivotal event was followed by ulceration and faulty wound healing in 73% of patients. Each year thousands of individuals with diabetes undergo amputation in VA facilities, resulting in substantial cost to the Department of Veterans Affairs and to themselves. If the VA is to address the prevention or delay of limb loss, the causal pathway information indicates that attention to the footwear of diabetic patients is necessary. PMID- 7869285 TI - Re-three-dimensional computer model of the human buttocks, in vivo by Beth A. Todd, PhD and John G. Thacker, PhD, Vol 31, No. 2, pp. 111-9, 1994. PMID- 7869286 TI - Trauma--the disease that was neglected. Progress: past and that to be. AB - Sir Harold Stiles has a historic spot in the annals of trauma care to which he and his military colleagues so richly contributed. For this we honour him today. Tremendous progress has been achieved during our lifetime in the field of trauma. Injury prevention has been the most important facet with progress underway in the fields of gun control, seatbelts, motorcycle and bicycle helmets, child restraint seats, airbags and particularly alcohol restraint. Overall, traffic fatalities are being reduced. Of great importance is the need for de-emphasis and deglamorization of violence by television, movie, and news media. Improved prehospital care has taken the form of professionalism of emergency medical services comparable to that in law enforcement and fire services. Improved hospital care is resulting, in part, from the widespread development of trauma and burn centres. Continued progress is needed in each field, particularly in gun control, alcohol control, overall traffic accident prevention, and in the understanding of cerebral oedema after head injury. The teaching of the principles of trauma prevention and community organization for better emergency medical response should be introduced into the Health or Civics curriculum perhaps at the 5th or 6th grade level in elementary schools. Perhaps the greatest potential for progress in the field of trauma which we have witnessed in our lifetime may prove to have been the actions of the United Nations in Korea in 1950 and Kuwait in 1991, proclaiming that 'war will no longer be tolerated as an instrument of national aggression'. PMID- 7869287 TI - Breast cancer in men in black Africa: a report of 73 cases. AB - Seventy-three Nigerian men with breast cancer seen over a 20-year period were studied to evaluate the pattern of the disease in one black African population. An annual incidence of 1.2 per 100,000 of the population was calculated; the proportion in relation to the disease incidence in women was 3.75%. Two-thirds of the patients were aged 50-65 years; the mean was 54.1 (SEM 2.3). Three patients linked their disease with trauma while seven had pre-existing gynaecomastia. More than 90% of the patients presented with advanced disease (stages III and IV), with bulky tumours (3.5-13.5 cm diameter), fixation to muscle (76.7%), skin involvement (65.6%) and nodal invasion (91.8%). Carcinomas of no special type (infiltrating ductal and undifferentiated cancers (76.7%)) dominated the histopathology, which included one case of lobular carcinoma. PMID- 7869288 TI - Laparoscopic cholecystectomy: laser or electrocautery? AB - Laparoscopic cholecystectomy is now an accepted part of general surgery. With the recent upsurge of interest in laparoscopic techniques, an optimum method of ensuring secure haemostasis is important particularly during dissection of the gall bladder from its mesenteric attachments. The use of laser to ensure haemostasis has been well practised in the treatment of peptic ulceration. Electrocautery is a time-honoured method of controlling local bleeding points by coagulation of tissue. The aim of this study was to assess whether one procedure showed any advantage over the other in terms of the length of operation time, postoperative drainage volume, time to dissect the gall bladder and length of the hospital stay. PMID- 7869289 TI - One lung ventilation in endoscopic transthoracic sympathectomy. AB - Endoscopic transthoracic sympathectomy currently requires one lung anaesthesia to facilitate access to the thoracic sympathetic chain. This may cause reduced perioperative arterial oxygen saturation. We describe a series of patients in which the collapsed lung is kept partially inflated using continuous positive airway pressure (CPAP) with 100% oxygen. This modification of anaesthetic technique enabled a normal arterial oxygen saturation to be maintained thus preventing operative delays whilst the lung was reinflated to restore adequate oxygen saturation. PMID- 7869290 TI - Ultrasound localization of screen detected impalpable breast tumours. AB - Accurate localization of a tumour is imperative before excision biopsy for impalpable breast lesions seen on screening mammography. Ultrasound localization has the advantages of being simple, quick and noninvasive. In a 3-year period from September 1989, 185 women have required localization of a breast tumour prior to biopsy, 159 were performed using a wire localization technique and 26 (14%) were performed using ultrasound alone. Twenty-two out of the 26 were malignant lesions. The mean maximum diameter of tumour diagnosed by ultrasound compared to histological sample was 10.6 mm (8.5-12.7*) to 11.1 mm (8.9-13.3*) with a correlation of r = 0.87. In the malignant cases the mean maximum diameter of tissue excised was 63.0 mm (57.2-65.9*). Complete excision was obtained in 21 out of the 22 patients with malignant disease by one operation. Ultrasound alone has been used successfully as a means of preoperative localization in selected cases prior to excision biopsy of a breast tumour. PMID- 7869291 TI - Surgical voice restoration: the Sunderland experience. AB - Surgical voice restoration following tracheo-oesophageal puncture is a well established procedure and the principal means of speech rehabilitation following laryngectomy and more recently laryngopharyngectomy. A valve prosthesis was used in 65 patients, 50 of whom underwent insertion at the time of surgery. Of the 65, 49 were men, 16 women and 15 have since died; the median length of follow-up of valves in situ has been 24.7 months (range 2-46 months). Of the 50 living patients 80% were using the valve at last examination. Complications arose in 52% but were generally minor and easily overcome. PMID- 7869292 TI - Some problems of tracheobronchoplasty for lung cancer in a Regional Hospital in Russia. AB - Tracheobronchoplastic procedures formed part of the operation for lung cancer in 41 patients of a Regional Hospital in Russia over the past 2 and a half years. Twenty-nine patients underwent sleeve lobectomy; in a further 12 patients, right pneumonectomy was combined with resection of other mediastinal structures. In 16 patients, sleeve lobectomy was indicated by the high risk of pneumonectomy. Involvement of the carina in the tumour indicated its resection. High frequency jet ventilation was a particular feature of anaesthesia for carinal resection. Omentopexy was used in 10 patients to prevent dehiscence of the bronchial anastomosis. Postoperative complications were encountered in 10 patients. The most frequent, in patients, was dehiscence of the tracheobronchial anastomosis after resection of the carina. Five patients died after operation, the causes of death being dehiscence of anastomosis, pneumonia, empyema, and acute heart failure. Despite the frequency of complications, tracheobronchoplastic operations are often the only possible option in the surgery of extensive lung cancer. PMID- 7869293 TI - Dislocation of the Austin Moore hemiarthroplasty: is closed manipulation justified? AB - In a retrospective study the outcome of 13 patients who underwent manipulation under anaesthesia (MUA) following dislocation of an Austin Moore hemiarthroplasty was determined. Nine patients died within 4 weeks of an MUA. Seven patients had a successful MUA, two patients without further complication. Six patients had an unsuccessful MUA. Four patients were discharged from hospital. The outcome following MUA of a dislocated uncemented hemiarthroplasty is poor. Subjecting elderly patients to an anaesthetic for a closed manipulation is a procedure of little clinical benefit. We were unable to define any selection criteria to improve the result. PMID- 7869294 TI - Intraoperative suction catheter tip contamination. AB - Suction catheter tip contamination is a potential source of intraoperative inoculation of wounds with bacteria. The continuous passage of large quantities of air through a blood-soaked catheter tip during the course of surgical procedures can lead to significant contamination. This in turn may contribute to late wound infection due to inoculation of the deeper recesses of the wound via the contaminated suction catheter tip. We have conducted a prospective clinical study to confirm the incidence of suction catheter tip contamination during orthopaedic trauma surgery and propose changes to current practice to reduce the incidence. PMID- 7869295 TI - Unusual acetabular component failure in hip arthroplasty. PMID- 7869296 TI - Rotaflex total knee arthroplasty: a report of two prosthetic failures at the hinge mechanism. AB - We present two cases of Rotaflex hinged total knee arthroplasties in which the components forming the hinge mechanism have fractured. In one case this was the high density polyethelene sleeve bush of the tibial bearing, the other case being the titanium retaining peg of the tibial component. Component failure in this design of prosthesis is previously unreported. PMID- 7869297 TI - Treatment and prognosis of lupus nephritis. PMID- 7869298 TI - Arthroscopy in rheumatology: a tool in search of a job. PMID- 7869299 TI - The reliability of the antiperinuclear factor test despite the inconstancy of the targeted antigens. PMID- 7869300 TI - CGP 47969A: effect on collagen induced arthritis in DBA/1 mice. AB - OBJECTIVE: CGP 47969A is a novel and potent inhibitor of cytokine biosynthesis in human and murine monocytic cells. The effect of CGP 47969A on collagen induced arthritis (CIA) in DBA/1 mice was investigated and compared to that of prednisolone. METHODS: CIA was induced by intradermal injection of type II collagen in CFA at Day 0. CGP 47969A was applied orally, 5 times/week, starting at Day 15 after immunization. Arthritic signs were recorded 3 times/week for clinical scoring and radiographic analysis was performed at the end of the experiment at Day 60. Serum amyloid P (SAP) and anticollagen antibody titers were determined by ELISA at Day 60. RESULTS: CGP 47969A dose dependently reduced the incidence of arthritis from 93% in the positive control group to 60, 40, 30 and 10% at doses of 1, 5, 25 and 60 mg/kg/day, respectively. At a dose of 120 mg/kg, CGP 47969A totally prevented the occurrence of arthritis (ED50 between 1 and 5 mg/kg). Prednisolone at 3 and 30 mg/kg reduced the arthritis incidence to 70 and 30%, respectively. CGP 47969A dose dependently inhibited the joint destruction, as measured by radiographic scoring and its potency was comparable to that of prednisolone. The elevated serum levels of the positive acute phase protein SAP in arthritic animals were completely normalized by CGP 47969A at a dose of 60 mg/kg, however, neither CGP 47969A nor prednisolone influenced the plasma levels of anticollagen antibodies (IgG). CONCLUSION: Our results demonstrate that CGP 47969A is highly effective in CIA with a potency comparable to that of prednisolone. These promising results justify the expectation that this novel antiarthritic compound now under development might also be effective in the treatment of rheumatoid arthritis in man. PMID- 7869301 TI - Analysis of the genes encoding the variable regions of human IgG rheumatoid factor. AB - OBJECTIVE: To better understand the immunoglobulin variable (V) region repertoire of rheumatoid factors (RF). METHODS: We characterized the heavy (H) and light (L) chain gene segments utilized in a monospecific IgG RF secreting hybridoma (AEE111F) which were derived from a patient with rheumatoid arthritis (RA). The hybridoma was established by fusion of a mouse myeloma cell line with bone marrow derived mononuclear cells from a patient with RA. First strand complementary DNA (cDNA) was generated and used for a polymerase chain reaction amplification of the H and L chain V domains. The amplified V domains were sequenced and compared with an extensive database of germline and cDNA V gene segments. RESULTS: The VH sequence was found to be 96% homologous to a previously described fetal VH3 cDNA (60P2). The VL sequence was also highly homologous to the previously described V lambda II gene (96%) derived from a patient with systemic lupus erythematosus which correlated with an 8.12 idiotype (Id), and to an antibacterial antibody against the Haemophilus influenzae type b capsular polysaccharide (94.7%). CONCLUSION: The overlap among this RF VL gene and the 2 reported V lambda sequences of antibodies that expressed anti-DNA related Id and an environmental pathogen specificity suggests that a part of the IgG RF isolated from patients with RA may thus be derived from the physiological natural antibody repertoire during an abnormal immune response and then develop high affinity, monospecific RF by the selection of an antigen driven mechanism. PMID- 7869302 TI - The clinical, serologic and radiologic features of rheumatoid arthritis in ethnic black Zimbabwean and British Caucasian patients. AB - OBJECTIVE: To compare the clinical, serologic and radiologic expression of rheumatoid arthritis (RA) in UK Caucasian and ethnic black patients from Zimbabwe. METHODS: Standardized protocols and assessment criteria were used to study 84 black patients with no non-Bantu antecedents and 84 UK Caucasian patients with RA (matched for disease duration, sex and age). RESULTS: Articular manifestations of RA were less severe in the black patients with RA from Zimbabwe as shown by less early morning stiffness (p = 0.001), fewer patients with > or = 3 active joints (p = 0.01), fewer joint deformities (p = 0.004) and better grip strength (p = 0.001) in comparison to the white patients with RA from the UK. Caucasian patients had a higher frequency of extraarticular manifestations (p = 1 x 10(-6)) including rheumatoid nodules (p = 0.0001), Raynaud's (p = 0.01) and Sicca syndrome (p = 0.001). Toxic effects from disease modifying antirheumatic drugs occurred less frequently in black patients (p = 0.0002). More white patients had Ro and La antibodies. The radiologic changes in the black patients were less severe than those in the white patients. The distribution of erosions in hands and feet were different in the 2 groups of patients studied. There were no differences between the urban and rural black patients but a more detailed study involving a large number of patients is required to confirm this observation. CONCLUSION: Black patients with RA from Zimbabwe have a disease that is clinically and radiologically less severe with fewer extraarticular features when compared to UK white patients. PMID- 7869303 TI - Clinical and biochemical response to single infusion of pamidronate in patients with active rheumatoid arthritis: a double blind placebo controlled study. AB - OBJECTIVE: To assess the effects of 3-amino-1-hydroxypropylidine-1,1 bisphosphonate (pamidronate) in rheumatoid arthritis (RA). METHODS: Thirty patients with active RA were randomly allocated to receive a single intravenous infusion of placebo, 20 mg pamidronate, or 40 mg pamidronate. RESULTS: Pamidronate treatment resulted in a rapid and sustained reduction in urinary calcium and hydroxyproline excretions. A sustained reduction in serum corrected calcium was only noted in the group treated with 40 mg pamidronate. In both groups treated with pamidronate a temporary increase in serum parathyroid hormone was noted. Compared to the placebo group clinical variables of disease activity improved significantly in both groups treated with aminohydroxypropylidine bisphosphonate. The erythrocyte sedimentation rate and serum C-reactive protein levels improved significantly in patients treated with 40 mg pamidronate. No serious side effects were documented. CONCLUSION: A single infusion of pamidronate in patients with RA is safe, suppresses bone resorption, and reduces disease activity. It is suggested that the effect on disease activity is dose dependent. PMID- 7869304 TI - Clinical heterogeneity of rheumatoid arthritis and the antiperinuclear factor. AB - OBJECTIVE: To assess the diagnostic and prognostic power of antiperinuclear factor (APF) and to identify a specific pattern of rheumatoid arthritis (RA) of different evolution and prognosis. METHODS: One hundred and fifty-nine sera from patients with RA, 280 sera from patients with other rheumatic diseases and 204 sera from healthy subjects were examined for APF. RESULTS: Sensitivity and specificity of the test were, respectively, 0.82 and 0.99 when 1:80 serum dilution was considered positive but 0.84 and 0.92 when tested at the currently used 1:5 serum dilution. According to the data obtained from APF and rheumatoid factor (RF) testing, patients with RA were subdivided in 4 groups. Clinical and demographic features for each group were analyzed. RF+ and/or APF+ patients showed a common pattern of disease, whereas RF-/APF- patients showed fewer extraarticular manifestations (p < 0.02) including Sjogren's syndrome (p < 0.04) and an unusual onset of the disease characterized by an involvement of large joints (p < 0.0001). Higher titer of APF was detected at the onset of the disease than in longstanding RA (p < 0.02). CONCLUSIONS: APF is a valuable diagnostic tool and a useful additional marker for RA. 1:80 serum dilution allows more specificity without substantial loss of sensitivity. A specific pattern of RA can be identified on the basis of APF status. PMID- 7869305 TI - Relationship of education level to treatment received for rheumatoid arthritis. AB - OBJECTIVE: To determine whether treatment received for rheumatoid arthritis (RA) is systematically different among individuals with different levels of formal education. METHODS: Using 4,455 patient-years of observational data from the University of California, San Francisco (UCSF) RA panel, we estimated the relationship between patients' education level and treatment received for RA. We define RA treatment broadly in terms of both the use of specific medications and use of health services. Independent variables include spouse's education level, as well as demographic, clinical, and socioeconomic characteristics, which are potential cofounders of this relationship due to associations with education level or RA treatment. RESULTS: Patients with RA with higher levels of formal education are more likely to be hospitalized or to undergo surgery for RA, even after differences in demographic, clinical, and socioeconomic characteristics are taken into account. In contrast, the use of specific medications was not systematically different among individuals with different education levels. CONCLUSION: The association of education level with use of health services may partially explain the association of education with RA outcomes. Further studies are needed to test this hypothesis formally. PMID- 7869306 TI - Combination therapy of cyclosporine with methotrexate and gold in rheumatoid arthritis (2 pilot studies). AB - OBJECTIVE: To evaluate the efficacy and toxicity of cyclosporine A (CyA) in combination with gold and methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: Twenty patients with RA with partial response to oral MTX and 20 patients with partial response to im gold had CyA added to their regimen for 6 months, withdrawn over 2 months and the patients monitored for 4 months. RESULTS: There was a significant improvement in joint count, joint score, joint swelling, grip strength and joint pain in patients taking the combination with no significant increase in adverse reactions. CONCLUSION: CyA in combination with gold or MTX may, over a 6 month period, increase efficacy in patients with refractory RA without significant increase in toxicity. PMID- 7869307 TI - Depressive symptoms in patients with systemic lupus erythematosus: association with central nervous system lupus and Sjogren's syndrome. AB - OBJECTIVE: To determine if patients with systemic lupus erythematosus (SLE) with depressive symptoms differ in regard to organ involvement and serological activity from other patients with SLE. METHODS: Disease manifestations were compared between 71 patients with SLE with a history of depressive symptoms and 278 patients without a history of depressive symptoms by univariate analysis and multiple logistic regression. RESULTS: Both univariate and logistic regression analysis revealed an association of depressive symptoms with neuropsychiatric lupus and secondary Sjogren's syndrome (SS). Patients with neuropsychiatric lupus had an adjusted odds ratio of 3.43 (95% CI 2.55, 4.63; p = 0.00005), and patients with secondary SS had an adjusted odds ratio of 2.97 (95% CI 2.08, 4.25; p = 0.0006) for depressive symptoms. No other organ involvement or serological abnormality was associated with depressed mood. CONCLUSION: These discrete associations of depressive symptoms with neuropsychiatric lupus and secondary SS suggest that depression does not occur purely as a response to social stresses, and may be a manifestation of autoimmune disease in some patients. PMID- 7869308 TI - The benefit of early treatment with immunosuppressive agents in lupus nephritis. AB - OBJECTIVE: In a cohort of 87 patients with lupus nephritis, delay between the detection of the onset of renal disease and renal biopsy was a significant predictor at the time of a first renal biopsy for subsequent renal insufficiency (relative risk - 4.9; 95% confidence interval = 1.7 to 14.5; p < 0.001) and death due to lupus renal involvement (relative risk = 6.7; 95% confidence interval = 2.1 to 21.2; p < 0.001). We evaluated the role of lead time bias, 2 variants of prognostic selection bias (length biased sampling), and the benefit of early treatment as explanations for this effect. METHODS AND RESULTS: Evaluation using the time of renal onset rather than the time of renal biopsy for the analysis suggested that lead time bias was unlikely to be an explanation for the effect of duration on renal insufficiency or death due to renal involvement. Identical values of age, serum creatinine and 24 hour urinary protein excretion at renal onset for those with a long duration versus short duration prior to biopsy, suggested that differences in prognostic selection were unlikely to explain the observed results. A 2nd type of prognostic selection bias arising from the failure to include patients who did not undergo a renal biopsy was further assessed by statistical simulation. The results of this approach indicated that prognostic selection bias was not solely responsible for the significant associations. Because treatment with high dose prednisone and immunosuppressive drugs was not instituted until a renal biopsy had been performed, delay in instituting these therapies remained a possible explanation for the increased frequency of renal insufficiency and death due to renal involvement observed in those with longer delays before renal biopsy. In addition, there was significant deterioration in serum creatinine (median change 0.6 mg/dl) and 24 hour urinary protein excretion (median change 2.5 gm) over the period from renal onset to renal biopsy, and significantly higher scores for the activity, chronicity and tubulointerstitial indices on renal biopsy in those in whom therapy was delayed. CONCLUSION: Prompt therapy with prednisone and immunosuppressive agents in lupus nephritis has a beneficial effect on longterm prognosis. PMID- 7869309 TI - Response to treatment as a predictor of longterm outcome in patients with lupus nephritis. AB - OBJECTIVE: To evaluate response to therapy over one year as a predictor of several longterm outcomes in lupus nephritis. METHODS: Response to treatment was evaluated by comparing serum creatinine and 24 h urine protein excretion at initial renal biopsy to those obtained after one year of treatment. Response at one year was evaluated as a predictor of renal failure, death due to lupus nephritis, and total lupus mortality, using survival analysis. RESULTS: Eighty five patients with lupus nephritis diagnosed between 1967 and 1983 and followed through 1990 were studied. Change in proteinuria was a powerful predictor of renal failure (p = 0.001) death due to lupus nephritis (p < 0.001) and overall lupus mortality (p = 0.001). In contrast to a recent study of patients selected for severe lupus nephritis, serum creatinine was not found to be of prognostic significance. CONCLUSION: Response of proteinuria to treatment over one year is a useful predictor of longterm outcomes in lupus nephritis. PMID- 7869310 TI - Antiendothelial cell antibodies and their relation to pulmonary hypertension in systemic lupus erythematosus. AB - OBJECTIVE: Antiendothelial cell antibodies (aECA) have been demonstrated in patients with systemic lupus erythematosus (SLE), but their role in the pathogenesis of this disease remains unclear. We investigated the association of aECA and anticardiolipin antibodies (aCL) with clinical and laboratory findings in patients with active SLE. METHODS: Sera from 28 patients with active SLE and 22 healthy controls were assayed for IgG and IgM-aECA by cellular ELISA method using cultured human umbilical vein endothelial cells and IgG-aCL by ELISA method. RESULTS: Serum titers of both IgG and IgM-aECA were significantly higher in active SLE than in healthy controls. Titers of IgG-aECA were unrelated to titers of IgG-aCL. Patients with pulmonary hypertension demonstrated a marked elevation of serum titer of both IgG and IgM-aECA compared with patients without pulmonary hypertension. In addition, patients with digital vasculitis showed a significant elevation of serum titer of both IgG and IgM-aECA compared with patients without digital vasculitis. Serum titers of IgG-aECA in patients with Raynaud's phenomenon and of IgM-aECA in patients with serositis were each significantly increased compared with patients without such findings. CONCLUSION: aECA were unrelated to aCL. Serum titers of aECA are elevated in patients with active SLE, especially with pulmonary hypertension, digital vasculitis, Raynaud's phenomenon or serositis. Since pulmonary hypertension in SLE has been associated with digital vasculitis, Raynaud's phenomenon and serositis, aECA may be involved in the pathogenesis of vascular injury, leading to these manifestations. PMID- 7869311 TI - Prolactin in systemic lupus erythematosus. AB - OBJECTIVE: To estimate the prevalence and evaluate the clinical significance of hyperprolactinemia in a cohort of 82 consecutively reviewed patients with systemic lupus erythematosus (SLE). METHODS: Basal prolactin levels and clinical data were analyzed in 82 consecutive patients with SLE, and longitudinal studies were carried out in 30/82 patients. RESULTS: Hyperprolactinemia was not associated with active disease in the group as a whole (p = 0.145) or in longitudinal studies in 30 patients (p = 0.294). However, SLE was more often active in patients with hyperprolactinemia without any obvious causes (8/9 samples) compared with patients with known secondary causes for hyperprolactinemia (p = 0.088). CONCLUSION: Hyperprolactinemia is likely not associated with disease activity in SLE. PMID- 7869312 TI - Antibodies to high mobility group proteins in systemic sclerosis. AB - OBJECTIVE: To determine the prevalence of autoantibodies to high mobility group (HMG) proteins in systemic sclerosis (SSc). METHODS: One hundred ninety-seven unselected sera from patients diagnosed as SSc (n = 180) or Raynaud's phenomenon (RP) (n = 17) were tested for HMG autoantibodies by ELISA and immunoblotting. RESULTS: Seventy-one of the 180 (39.0%) SSc sera bound to HMG proteins in an ELISA: 56 (31%) to HMG-1 and/or HMG-2; 29 (16%) to HMG-14/17. In the same assay, 7 of 17 RP sera (41%) bound to HMG proteins: 4 (23%) to HMG-1 and/or HMG-2, and 5 (29%) to HMG-14/17. The specificity of HMG binding was confirmed by immunoblotting. CONCLUSION: Antibodies to HMG proteins, particularly to HMG-1 and HMG-2 are found in about 1/3 of SSc Sera. Since HMG-1 and HMG-2 have a role in transcription, these observations further implicate transcriptional complexes as targets of autoantibodies in scleroderma. This is the first published report of HMG autoantibodies in scleroderma. PMID- 7869313 TI - Increased jejunal secretory IgA and IgM in ankylosing spondylitis: normalization after treatment with sulfasalazine. AB - OBJECTIVE: To investigate the intestinal immune system in patients with ankylosing spondylitis (AS) and the influence of sulfasalazine treatment. METHODS: Total IgA, secretory IgA and IgM and secretory component were determined in jejunal perfusion fluid in 19 patients with AS before and after 3 months' treatment with sulfasalazine and compared with 18 healthy control subjects. Serum immunoglobulins and inflammatory activity were measured with standard methods and compared with a clinical scoring of disease activity. RESULTS: Total IgA, secretory IgA, IgM and secretory component were significantly increased in the lavage fluid when compared with healthy controls. Treatment with sulfasalazine normalized these alterations. CONCLUSION: Our findings demonstrate that the intestinal immune system is activated in AS and that such activation can be influenced by treatment. This observation supports the idea that antigenic stimulation in the gut is a possible causative event in AS. PMID- 7869314 TI - Antibodies to Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis in ankylosing spondylitis: effect of sulfasalazine treatment. AB - OBJECTIVE: To make a longitudinal study of antibodies to Klebsiella pneumoniae in patients with ankylosing spondylitis (AS) and to assess treatment effects. As a comparison we measured antibodies of 2 other gut associated bacteria, Escherichia coli and Proteus mirabilis. METHODS: In a double blind study in 84 Finnish outpatients with AS before and after 26 weeks' treatment with sulfasalazine or placebo we measured serum antibodies to Klebsiella pneumoniae, E. coli and Proteus mirabilis with ELISA: Serum samples of 100 healthy blood donors served as controls. RESULTS: The levels of IgA class antibodies to all 3 bacteria were statistically significantly higher in the sera of the patients compared to the controls. During sulfasalazine treatment significant decreases were observed in concentrations of the IgA class antibodies to Klebsiella and E. coli whereas only a slight decrease was observed in the concentrations of IgA antibodies to Proteus mirabilis. There were no correlations between the clinical and laboratory results observed with sulfasalazine and decrease in concentrations of IgA class antibodies. CONCLUSION: Our results agree with the role of gut associated lymphoid tissue in the pathogenesis of AS, but do not totally exclude Klebsiella pneumoniae as a specific agent contributing to the development of AS. PMID- 7869315 TI - Early recognition of sacroiliitis by magnetic resonance imaging and single photon emission computed tomography. AB - OBJECTIVE: To evaluate the role of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) in the detection of sacroiliitis in patients with clinical features of inflammatory back disease but without conventional radiographic changes. METHODS: Twenty-four patients with inflammatory low back pain (ILBP) and normal or suspicious changes of sacroiliitis (New York criteria: 0-1) on conventional radiography, in addition to 12 control subjects were studied. MRI, bone and SPECT scans of the sacroiliac (SI) joints were obtained and interpreted without knowledge of patient identification. MRI scans were scored according to the modified New York criteria and examined for the presence of joint fluid, abnormalities in articular cartilage and in the underlying marrow signal. A quantitative and qualitative assessment of radiopharmaceutical uptake in the SI joints was derived from planar bone scan films and SPECT scans. RESULTS: MRI detected features of scaroiliitis in 54% of patients with ILBP and in 17% of controls (p = 0.07). Quantitative and qualitative analysis of planar bone scan films did not reveal any differences between the 2 patient groups. In contrast, SPECT scanning identified sacroiliitis in 38% of patients with ILBP compared to none in controls (p = 0.05). When MRI and SPECT scanning were combined there was evidence of sacroiliitis in 63% of patients with ILBP and in 17% of controls (p = 0.025). CONCLUSION: MRI and SPECT bone scanning provide objective and complementary evidence of sacroiliitis in patients with clinical features of inflammatory spinal disease in the absence of conventional radiographic changes. PMID- 7869316 TI - The collagen types in the attachment zone of rotator cuff tendons in the elderly: an immunohistochemical study. AB - OBJECTIVE: The attachment zone of the rotator cuff tendons in the elderly was studied immunohistochemically in order to determine how degenerative changes affected the pattern of collagen fiber distribution. METHODS: Twenty-seven cuffs with their bony insertion were obtained from 22 postmortem cases of both sexes ranging in age from 52 to 90 years and without a history of shoulder ailments. In addition, 3 cuff specimens from cadavers in the 3rd and 4th decades were examined for comparison. Sections of formalin fixed tissues were stained by peroxidase antiperoxidase (PAP) technique using monoclonal antibodies against types I, II and III collagen. RESULTS: Degenerative changes affecting the fibrocartilage primarily were characterized by calcification, fibrovascular proliferation and microtears. In addition, they were found in all the cuff tendons of elderly individuals but not in those from younger subjects. Immunohistochemically, the attachment zone in areas without degenerative lesions showed collagen type I labelling strongly in bone but only moderately in the fibrocartilage. The predominant labelling in the fibrocartilage was for collagen type II, and collagen type III labelled principally in perichondrocytic areas. The tide-mark showed inconsistent labelling for any of the collagen types. In the presence of degenerative lesions, the disposition of fiber types was interrupted by calcification and microtears. Collagen type II composition of the fibrocartilage was markedly altered by the presence of fibrovascular tissue which labelled only for collagen type III. CONCLUSION: We conclude that severe degenerative changes in the cuff tendons of elderly individuals, alter the collagen characteristic of the rotator cuff and that the changes could be associated with impairment of biomechanical properties of the attachment zone, and may give rise to the clinical syndrome of enthesopathy. PMID- 7869317 TI - Ontario patients' acceptance of waiting times for knee replacements. AB - OBJECTIVE: To determine waiting times for an initial orthopedic consultation and subsequent knee replacement surgery in Ontario and patients' acceptance of these waiting times. METHODS: Mailed patient survey to 185 randomly selected knee replacement recipients discharged from 5 Ontario hospitals between 1985 and 1990, with telephone followup after 2 mailings, implemented between May and July, 1992. Patients were asked about waiting times for their initial orthopedic consultation and subsequent knee replacement surgery and their acceptance of these waiting times. RESULTS: Of the 185 patients, 40 were excluded because they were deceased, unable to respond, or not traceable. Of the 145 eligible patients, 127 or 87.6% responded. The median waiting times for an initial consultation and for knee replacement surgery were 4.0 and 9.5 weeks, respectively. Waiting times did not change significantly over the 5-year study period (Pearson correlation coefficients: 0.07, p = 0.53, for consultation, and -0.08, p = 0.44, for surgery). The waiting times for consultation and surgery were acceptable to 93.2% (95% confidence interval: 88.7-97.7%) and 88.1% (95% confidence interval: 82.3 93.9%) of respondents, respectively. The average acceptable surgical waiting time of 13.2 weeks was significantly shorter than the not acceptable average of 34.3 weeks (p < 0.001). CONCLUSION: The average waiting periods for an initial orthopedic consultation and subsequent knee replacement surgery were relatively short, and the majority of patients considered their waiting times acceptable. PMID- 7869318 TI - A comparative study of signal versus aggregate methods of outcome measurement based on the WOMAC Osteoarthritis Index. Western Ontario and McMaster Universities Osteoarthritis Index. AB - OBJECTIVE: To compare signal versus aggregate measurement strategies using the VA3.0S version of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis (OA) Index. METHODS: Seventy patients with OA of the knee were asked to identify a signal item for each of the 3 dimensions of the WOMAC OA Index at baseline and termination of a 12-week, double blind, randomized, controlled trial. RESULTS: The signal method detected statistically significant alterations in health status at relatively small sample sizes and with a relative efficiency close to or at unity. In addition to a low prevalence of deterioration in nonsignal items, we observed some inconsistency in signal selection. CONCLUSION: Signal methods of measurement may provide an alternative approach to outcome measurement provided issues of nonsignal deterioration and the consistency of signal selection can be addressed. PMID- 7869319 TI - Serial kinematic analysis of the canine knee after L4-S1 dorsal root ganglionectomy: implications for the cruciate deficiency model of osteoarthritis. AB - OBJECTIVE: To characterize knee movements before and after unilateral hindlimb deafferentation in dogs with stable joints. METHODS: High speed cinematography and frame by frame analysis were used to analyze knee kinematics of 6 dogs serially for 26 weeks following L4-S1 dorsal root ganglionectomy, which was performed to deafferentate one hindlimb. RESULTS: Overall knee movements were not reduced, but knee extension increased during most of the gait cycle. Few changes occurred in knee velocity, and none at touchdown or during weight acceptance. CONCLUSION: We previously showed that unilateral hindlimb deafferentiation does not cause osteoarthritis or reduce ipsilateral peak vertical forces in dogs with stable knee joints over an observational period of 16 months. We now show that joint protection in the deafferented stable joint occurs, paradoxically, in the presence of increased knee extension. We conclude that whereas sensory nerves may limit knee extension during ambulation, the health of the joint is not dependent upon this "extension limiting" function. PMID- 7869320 TI - A single infusion of bisphosphonate AHPrBP in the treatment of Paget's disease of bone. AB - OBJECTIVE: To assess the efficacy of single infusion of bisphosphonate AHPrPB (APD) (60 mg) in active Paget's disease of bone. METHODS: Twenty-six patients with symptomatic Paget's disease of bone were treated with a single infusion of APD (60 mg) over 12 h and were assessed for clinical as well as biochemical improvement for a mean period of 2 years. Treatments were repeated if relapse occurred during followup. RESULTS: Bone pain improved in 92% of patients within one month and over 76% of patients had no pain at 6 months. Serum alkaline phosphatase fell to normal level in 78% of patients at 6 months and about 77% at one year. Further treatment with intravenous (iv) APD (60 mg) was given for relapse in 7 patients at one year, 13 at 18 months and 2 at 24 months. CONCLUSION: Our prospective study demonstrates that 60 mg APD given iv is an effective, simple, safe and less expensive treatment for active Paget's disease of bone and this therapy may well be given in a daycare unit or an outpatient setting. PMID- 7869321 TI - Lymphocyte subpopulations in patients with primary fibromyalgia. AB - OBJECTIVE: Fibromyalgia (FM) is a clinical entity of unknown etiology frequently diagnosed in rheumatology. The potential involvement of the immune system in its pathogenesis has been suggested. Studies of abnormal T cell subpopulations often have been inconclusive. We attempted to clear this point by comparing lymphocyte subpopulations, including some of the newer activation markers, in patients with FM and healthy controls. METHODS: Sixty-five patients with FM and 56 healthy controls were studied. Flow cytometry was used as a quantification technique to measure lymphocyte subpopulations, CD3 (T cells), CD19 (B cells), CD16 (natural killer cells), CD4 (T helper/inducer cells), CD8 (T cytotoxic/suppressor cell), CD25 (interleukin 2 receptor), CD69 (activation inducer molecule marker), CD71 (transferrin receptor) and CD54 (ICAM-1); CD4/CD8 ratios were also estimated. RESULTS: The number of T cells expressing activation markers CD69 and CD25 was decreased in patients with FM; the other subpopulations were similar in patients and controls. CONCLUSION: Our results suggest a defect in T cell activation in patients with FM. PMID- 7869322 TI - Pituitary release of growth hormone and prolactin in the primary fibromyalgia syndrome. AB - OBJECTIVE: Previously, we demonstrated hyperreactive adrenocorticotropic hormone (ACTH) release in patients with primary fibromyalgia syndrome (primary FMS). We investigated the pituitary release of growth hormone (GH) and prolactin (PRL) in search of further disturbances in neuroendocrine reactivity possibly associated with the pathophysiology of primary FMS. METHODS: Ten female patients with primary FMS fulfilling the 1981 Yunus criteria and 10 matched, healthy and sedentary controls were subjected to an insulin induced hypoglycemia test; samples for measurement of glucose, GH and PRL were taken at intervals. RESULTS: Compared to the controls, the patients with primary FMS displayed significantly lower basal GH levels, whereas their basal PRL levels were slightly, though significantly, higher (respectively p = 0.021 and p = 0.041). Following hypoglycemia, there was a marked, statistically highly significant (p = 0.001), hyperreactivity of the GH response in patients with primary FMS. The PRL response showed wide interindividual variation and did not differ between patients and controls. CONCLUSION: Our findings indicate that fibromyalgia, along with ACTH hyperreactivity, also exhibits a distinct disturbance in the GH-somatomedin C axis. With regard to PRL, the variation in individual responses limits conclusions. The hyperreactive response patterns of GH and ACTH previously suggest a common origin, which might be related to a subtle glucocorticoid deficiency. PMID- 7869323 TI - The effects of Arthritis Society fellowships on career choice. AB - OBJECTIVE: To find out if The Arthritis Society (TAS) fellowship grants influenced career choice or career development. METHODS: Two hundred former TAS training fellowship recipients (1975-1990 inclusive) were sent a questionnaire to evaluate the effects of TAS clinical or research fellowship support on their subsequent career development. RESULTS: One hundred and forty (70%) completed questionnaires were returned by 88 clinical and 37 research fellowship recipients -a further 17 had received both a clinical and a research fellowship. Fifty-one percent of the respondents are now academic rheumatologists, 40% in community practice and 9% still in training. Seventy-three percent of the research fellowship recipients currently receive research grant support, compared to 16% of the former clinical fellowship recipients. Seventy-one percent agreed that their TAS fellowship support had "directly or indirectly influenced or facilitated their chosen career path"--this included 100% of the research fellowship recipients, compared to 55% of the clinical fellowship recipients. The majority decided on an academic or a community based career path during their postgraduate training. Fourteen percent who trained for an academic career are now in community practice and 9% who planned on a community based career later became academic rheumatologists. Eighty-nine respondents (64%) enclosed a CV. This subset was further analyzed using career markers such as academic rank, number and size of research grants and number of publications. In this subset those who had received both a clinical and a research fellowship had the most advanced academic rank (22% full professor), largest number of publications (n = 39) and largest number of grants (5.3/year; average $40,446), compared to former research fellowship recipients: 4.0% full professor, 22 publications, 3.2 grants/year; average $25,164. Recipients of clinical fellowships in this subset had lower levels of all the academic career markers. CONCLUSION: Of 200 consecutive TAS fellowship recipients 71% of those responding (n = 140) to a career tracking study agreed that the fellowship support "directly or indirectly" influenced or facilitated their career choice. An apparent synergistic effect of providing both clinical and research fellowships on subsequent development of an academic career deserves further study. PMID- 7869324 TI - A novel autoantibody to the putative oncoprotein DEK in pauciarticular onset juvenile rheumatoid arthritis. AB - OBJECTIVE: To define the frequency of a novel autoantibody reactive with a 45 kDa protein in children with juvenile rheumatoid arthritis (JRA). This protein is expressed by the putative oncogene DEK associated with a subtype of acute myeloid leukemia. METHODS: The sera of 158 children with JRA were analyzed for the presence of anti-DEK by immunoblotting using purified DEK protein and compared with sera of 109 children with other rheumatic diseases and 25 healthy controls with no connective tissue disease. RESULTS: Antibodies to DEK were found significantly more frequently among children with JRA than among children with other rheumatic diseases or controls (p < 0.001). Among children with JRA, anti DEK was significantly more often associated with pauciarticular onset than with poly-articular and systemic onset subtypes (77 vs 29 and 8%, respectively, p < 0.001). Anti-DEK was no more frequent among children with pauciarticular JRA complicated by iritis than among those without iritis (88 vs 71%, respectively). The frequency of anti-DEK in other rheumatic diseases varied from 0 in children with spondyloarthritis to 31% in scleroderma. CONCLUSION: Antibodies to DEK are highly associated with pauciarticular onset JRA. PMID- 7869325 TI - Incidence of systemic connective tissue diseases in children: a nationwide prospective study in Finland. AB - OBJECTIVE: To study the incidence of systemic connective tissue diseases (CTD) and of systemic onset juvenile arthritis (S-JA) in children aged 0 to 15 years. METHODS: A nationwide, prospective, hospital based series of new patients from Finland collected during a 4-year period and supplemented with data from the National Hospital Discharge Register. The population at risk was 1.02 million. Classification criteria developed for adult CTD and the American Rheumatism Association criteria for JA were used. RESULTS: The annual incidence rates found were as follows: systemic lupus erythematosus 0.37, polymyositis/dermatomyositis (PM/DM) 0.30, mixed connective tissue disease 0.10, scleroderma 0.05, and S-JA 0.47/100,000. Girls outnumbered boys in the whole series of CTD (24:9) and also in S-JA (11:8), but in PM/DM the sex distribution was even. CONCLUSION: CTD and S JA are rare before the age of 16 years. From the present incidence figures and those recently published for JA the incidence of CTD is estimated to be between 4 and 7% of that of JA, and S-JA accounts for only 2 to 4% of all JA. PMID- 7869326 TI - Cardiac function in systemic lupus erythematosus. AB - Cardiovascular disease is one of the main causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). The observation that the disease may affect all cardiac tissues, although frequently in a subclinical fashion, has come to attention only recently after the introduction of non invasive sensitive cardiac imaging technology in clinical practice. We review the current perspective of this topic, placing special emphasis on what is known and what is not known regarding cardiac disease in the pediatric population with SLE. Our current lack of information calls for the initiation of collaborative research in this area. PMID- 7869327 TI - Antihistone antibody profile in sulfasalazine induced lupus. AB - Two patients developed drug induced lupus secondary to sulfasalazine (SSZ). One patient was receiving SSZ for Crohn's disease and was subsequently treated with olsalazine, which lacks the sulfapyridine component of SSZ. Her inflammatory bowel disease (IBD) remained controlled and she did not develop a recurrence of lupus, suggesting that olsalazine is safe in patients with IBD and a history of SSZ induced lupus. The SSZ induced antibodies were predominantly IgG against the (H2A-H2B)-DNA complex. Since lupus induced by 7 other drugs was associated with a similar antibody response, our findings support the existence of a common pathway for autoantibody induction. PMID- 7869328 TI - Systemic therapy with fibrinolytic agents and heparin for recalcitrant nonhealing cutaneous ulcer in the antiphospholipid syndrome. AB - Skin ulceration is a cutaneous manifestation of the antiphospholipid syndrome (APS) and is associated with thrombosis of small dermal vessels. Numerous therapeutic agents have been used but are often ineffective. We describe the efficacy of heparin and fibrinolytic agents [urokinase and tissue plasminogen activator (tPA)] in the treatment of longstanding nonhealing cutaneous ulcers. In one patient, heparin plus low dose tPA resulted in healing. In another patient, treatment first with urokinase and heparin, and subsequently with tPA alone, resulted in healing. When the ulcer recurred secondary to severe peripheral edema, tPA plus heparin led to complete resolution of the ulcer. This suggests that fibrinolytic therapy and/or heparin may be useful in other recurrent thrombotic manifestations of the APS as well. However, it must be emphatically stressed that since life threatening adverse reactions can occur secondary to hemorrhage, this treatment should be undertaken only after extensive evaluation and close monitoring of the coagulation status. PMID- 7869329 TI - Antiphospholipid antibody syndrome associated with ovarian cancer. A new paraneoplastic syndrome? AB - We describe a 41-year-old woman, in whom antiphospholipid antibody syndrome (APS) occurred at presentation, before the detection of an ovarian endometrial adenocarcinoma. This syndrome was characterized by widespread and worsening thromboembolism and it did not respond to conventional anticoagulant treatment. The paraneoplastic nature of this APS was strongly suggested by the disappearance of both thromboembolism and antiphospholipid antibodies only after surgical removal of the cancer. PMID- 7869330 TI - Intraarticular apatite crystal deposition as a predictor of erosive osteoarthritis of the fingers. AB - Two patients are described who presented with a chronic effusion with calcium containing particles, considered as apatite, in one finger joint. After a followup of several years, these joints presented erosive changes on radiographs, which raises the question of the pathogenic role of apatite crystals. PMID- 7869331 TI - Malignant ventricular arrhythmia in systemic sclerosis controlled with an implantable cardioverter defibrillator. AB - The prognosis of systemic sclerosis (SSc) is poor, and a significant number of patients suffer sudden death, probably related to malignant ventricular arrhythmias for which there is no reliable drug treatment. We describe a patient with SSc who had 2 documented episodes of ventricular fibrillation, that reverted after electrical defibrillation. An electrophysiological study performed after 3 weeks of oral loading with amiodarone 1200 mg/day, demonstrated the induction of unstable sustained syncopal ventricular tachycardia. She has been successfully controlled with the implant of a 3rd generation implantable cardioverter defibrillator. We suggest that this treatment should be seriously considered in those patients with SSc and malignant ventricular arrhythmias unresponsive to drug therapy. PMID- 7869332 TI - Aberrant control of galactosyltransferase. PMID- 7869333 TI - Graves' disease following silicone breast implantation. PMID- 7869334 TI - Olsalazine in Reiter's syndrome. PMID- 7869335 TI - Ribeiro & Kidwell's transposon model. PMID- 7869336 TI - New species of Neotrombicula (Acari: Trombiculidae) from African primates (Galagidae and Cercopithecidae). AB - Neotrombicula kenyaensis Goff and Neotrombicula centrafricana Goff are described as new from specimens collected from the primates Galago senegalensis E. Geoffroy (Fam. Galagidae) in Kenya and Allenopithecus nigroviridis (Pocock) (Fam. Cercopithecidae) in Central Africa, respectively. PMID- 7869337 TI - Reduction of immature Ixodes scapularis (Acari: Ixodidae) in woodlots by application of desiccant and insecticidal soap formulations. AB - The efficacy of two commercially available formulations of a desiccant and insecticidal soap were compared with chlorpyrifos wettable powder (0.6 kg [AI]/ha) against the immatures of Ixodes scapularis Say in a woodlot in Westchester County, New York. The desiccant formulation (Drione) was applied at 61.04 kg/ha and an insecticidal soap (Safer's) was applied as a mixture (39 ml concentrate per liter of water) at 107 liters/ha. By 1 wk after application, all treatments significantly reduced the density of nymphs in comparison to untreated plots. Only plots treated with chlorpyrifos had significantly reduced nymphal densities 2 wk after application. By 6 wk after application, there were no differences in nymphal density between treated and untreated plots, which was likely the result of a decline in overall nymphal populations. None of the treatments against nymphs affected larval densities sampled 6 wk after application. Larval density was significantly lower 1 wk after application in plots treated with chlorpyrifos and Safer's insecticidal soap than in untreated plots. By 2 wk after treatment, only plots treated with chlorpyrifos had lower larval densities than untreated plots. Results indicate that the desiccant Drione and Safer's insecticidal soap are good for short-term control of immature I. scapularis. PMID- 7869338 TI - Species identification of calliphorid (Diptera) eggs. AB - Eggs of 11 forensically important calliphorid species belonging to six genera were studied with SEM for useful diagnostic characters. Identification was confounded by the following three factors: (1) variability within and among populations of the same species, (2) similarities among some congeneric species, and (3) similarities between some species of different genera. Reliable separation based on morphology should take into account relevant aspects of blow fly biology as it is affected by locality, climate, season, and weather. PMID- 7869339 TI - Estimates of population size, dispersal, and longevity of domestic Aedes aegypti aegypti (Diptera: Culicidae) by mark-release-recapture in the village of Shauri Moyo in eastern Kenya. AB - Estimates of the absolute size of a domestic population of Aedes aegypti aegypti (L.) were made in the Rabai area of Kenya, based on a single release, followed by either single or repeated recaptures. From single recapture within 24 h of release, the size of the female Ae. a. aegypti population in the Shauri Moyo village was estimated by the Lincoln index to be 365. Using a single release and repeated recaptures, population size was estimated by Jackson's positive method to be 337. Depletion of the unmarked females by daily removal sampling provided us with two additional, direct estimates of the size of the village population (451 by Kano's method and [464 +/- 18.9 SEM] by the Moran-Zippin method). The longevity of marked females was at least 9 d. The day-to-day movement of marked mosquitoes revealed the dispersal pattern of Ae. a. aegypti among houses clustered within different distance zones. Marked mosquitoes reached all houses of the village within 24 h of release. After 5 d, the dispersion of both marked and unmarked mosquitoes among houses was similar. PMID- 7869340 TI - Response of Sarcoptes scabiei var. canis (Acari: Sarcoptidae) to lipids of mammalian skin. AB - Bioassays were conducted to determine if Sarcoptes scabiei (L.) were attracted to lipid compounds that occur in or on the epidermis of human or other mammalian skin. Seventeen lipid compounds attracted S. scabiei including odd and even carbon chain lengths and saturated and unsaturated fatty acids, fatty acid methyl esters, a steroid, a steroid precursor, and a triglyceride. The attractive saturated fatty acids were pentanoic (5:0), hexanoic (6:0), octanoic (8:0), lauric (12:0), pentadecanoic (15:0), and stearic (18:0) acids. The unsaturated fatty acids oleic (18:1 delta), linoleic (18:2 delta), and arachidonic (20:4 delta) acids also attracted scabies mites. No concentration of sebacic (10:0), myristic (14:0), palmitic (16:0), or arachidic (20:0) acids attracted any life stage of S. scabiei. Five fatty acid methyl esters attracted at least one life stage of mites. Cholesterol and squalene, its transient precursor, were both attractive as was the triglyceride, tripalmitin. The molar concentration of lipids that elicited the greatest response by a particular life stage varied between compounds (ranging from 1 to 0.0001 M). Some lipids were attractive at several concentrations, whereas for others a response was elicited by only one concentration. A comparison of different life stages showed that adults, especially females, were attracted more than immatures to most of the compounds. The data show that lipids that occur in the epidermis of human or other mammalian skin attract scabies mites. Therefore, host skin lipids may contribute to host specificity, attract mites to specific anatomical areas of the body, or play key roles in other host-parasite relationships. PMID- 7869341 TI - Sensitive and specific colorimetric dot assay to detect eastern equine encephalomyelitis viral RNA in mosquitoes (Diptera: Culicidae) after polymerase chain reaction amplification. AB - A sensitive and specific colorimetric dot assay following polymerase chain reaction (PCR) method has been developed to detect 0.1 pg of eastern equine encephalomyelitis viral (EEEV) RNA. The assay is 250-fold more sensitive than analysis by electrophoresis and is based on converting a 291-nucleotide sequence of the viral coat protein amino terminus into a double-stranded DNA (dsDNA) and amplifying the DNA using a specific primer pair and PCR. The amplified complementary DNA (cDNA) is denatured adsorbed onto a nylon strip, baked, and detected with a digoxigenin-labeled probe. Dots with viral cDNA are stained dark red, whereas controls do not stain or stain lightly. The assay is very specific and sensitive and detects only EEEV. RNA of Venezuelan equine encephalitis, St. Louis encephalitis, Keystone, Flanders, Tensaw, and western equine encephalitis viruses were not detected. EEEV (Ten Broeck) RNA was detected at the 10-ng level, indicating that the prototype we used may have different nucleotides in the region where the primer pair binds. The PCR amplified EEEV cDNA that was 92% homologous to the consensus sequence of EEEV. The detection of EEEV in the liver of an infected Emu bird and in field-collected mosquitoes from Florida and Massachusetts that were analyzed concurrently as blind samples by tissue culture plaque assay and by PCR dot analysis proved that the assay is sensitive and can be used to detect infected mosquitoes. The assay can detect at least 1 infected mosquito in a pool of 1,000 uninfected mosquitoes. PMID- 7869342 TI - Effect of deer exclusion on the abundance of immature Ixodes scapularis (Acari: Ixodidae) parasitizing small and medium-sized mammals. AB - Effects of deer exclusion on abundance of immature Ixodes scapularis Say parasitizing small and medium-sized mammals, and the role mammals have in introducing ticks to exclosure areas, were examined at two sites in Westchester County, New York. In total, 686 mammal captures representing nine species were obtained, with white-footed mice, Peromyscus leucopus Rafinesque, composing > 80% of all captures, followed by raccoons, Procyon lotor (L.); opossums, Didelphis virginiana (Kerr); and striped skunks, Mephitis mephitis Schreber. At the Near Archives site, 14% of 81 individual mice, 46% of raccoons, and 33% of opossums captured were found to cross the exclosure fence, as did 12% of 50 mice and 38% of raccoons at the Hudson Pines site. Skunks apparently did not cross the fence at either site. Mice captured exclusively outside the Near Archives exclosure hosted significantly more larvae than mice captured inside only, with fence crossers hosting an intermediate number of larvae. At Hudson Pines, numbers of larvae on fence-crossing mice and those captured solely inside the exclosure were equivalent, with tick loads on mice captured outside the exclosure significantly greater. The number of larvae per raccoon did not differ significantly with capture location (inside, outside, or both sides of exclosure fence) at either site. Densities of host-seeking larvae and nymphs were significantly higher outside the exclosure than inside at Near Archives, though not at Hudson Pines. Differences in tick density inside and outside exclosures declined with each successive developmental stage so that adult density inside exclosures tended to converge with that outside at both sites. Although deer exclosures can have a significant impact on nymphal I. scapularis abundance, they may not reduce the risk of encountering infected adults. Mice, raccoons, and opossums have a role in introducing potentially infective ticks to areas where deer have been excluded, though the level of immigration of ticks into the area will likely depend on the density of ticks outside the exclosure. PMID- 7869343 TI - Behavior on approach to surface prey by larvae of Toxorhynchites amboinensis and T. brevipalpis (Diptera: Culicidae). AB - Behavior of Toxorhynchites amboinensis (Doleschall) and Toxorhynchites brevipalpis (Theobald) larvae (starved 48 h) as they approach and capture surface prey is described quantitatively from videotaped records. Of 106 T. amboinensis and 82 T. brevipalpis larvae observed, 84.9 and 97.6%, respectively, responded to the presence of surface prey within 2 min (most < 20 s). Once they detected prey, larvae executed initial backward swims if prey was rearwardly positioned, then approached it in a series of undulatory forward swims with progressive adjustments of body angle so that the final movements were directly toward the prey. Swims consisted of an active phase, during which propulsive bodily flexions were made and a passive one of continued inertial drift after active motion had ceased. Quantitative changes in the nature of the swims in terms of interval separating active phases and also distances, times, and speeds throughout the approach sequence were analyzed from the video tapes. T. brevipalpis responded to the presence of prey more rapidly, captured prey in less time, and approached prey more rapidly, with shorter rest periods between active swim phases than T. amboinensis. The behavior indicated that Toxorhynchites larvae are able to assess both the angle to surface prey and its distance and that they interpolate this information to optimize the approach path. The degree of refinement in this behavior indicates that it is well adapted to take advantage of the important surface food source in nature. In this phase of their feeding, Toxorhynchites larvae are active hunters and are not entirely the passive ambush predators they have seemed to be from many studies that have used other mosquito larvae as (subsurface) prey. PMID- 7869344 TI - Seasonal activity of nymphal Ixodes scapularis (Acari: Ixodidae) in different habitats in New Jersey. AB - Activity patterns of nymphal Ixodes scapularis Say were compared between habitat types (dominant tree types: mixed deciduous, oak, white pine, red cedar, sassafras, and spicebush). Both the time of peak abundance and the relative abundance of questing nymphs at the peak were compared. Several smoothing algorithms were tested with the data to determine if they could be used to estimate the time of peak abundance more accurately. Determination of the time of peak abundance using the raw data or simple moving averages was susceptible to outliers. Weighted averages were less susceptible to outliers. The seasonal pattern of nymphal abundance was similar in all habitat types. Variation in the time of peak abundance between habitats was low. Peak densities were lower in deciduous habitats (0.24 +/- 0.05 nymphs per square meter) than in nondeciduous habitats (0.85 +/- 0.15 nymphs per square meter); this could have resulted from higher host use of the nondeciduous areas. These data suggest that there are differences in the population dynamics of nymphs found in different habitats. PMID- 7869345 TI - A re-appraisal of the biological activity of bacteroides LPS. AB - Lipopolysaccharides (LPS) were extracted from seven Bacteroides strains by three different techniques: the phenol-water (PW), phenol-chloroform-petroleum (PCP) and Triton-Mg2+ methods. The strains selected included two different B. fragilis strains, one of which was grown in two different media. Yields varied between the strains, growth media and extraction technique, but generally the highest yield by weight was from the PCP method and the lowest from the PW method. The PW method was selected for the greatest amounts of carbohydrate and KDO, and the PCP method for the least. Phosphorus levels were more uniform among all extraction methods. Protein contamination was found in all Bacteroides LPS extracts, with extremely low levels in PW-LPS and the highest levels in material extracted by the PCP and Triton-Mg2+ techniques. No protein contamination could be detected after proteinase K treatment. After silver staining LPS PAGE profiles showed ladder patterns characteristics of smooth LPS for B. vulgatus, B. thetaiotaomicron and the control Escherichia coli O18:K- strains, whereas the other Bacteroides strains showed mainly rough and low M(r) material only. The PCP method did not select for high M(r) material in the B. fragilis strains; otherwise the LPS profiles for all extraction methods were identical. The biological activities of native and sodium salt form LPS were investigated on a weight for weight basis and compared to that of E. coli O18:K- PW-LPS. Amongst the LPS from Bacteroides strains, those prepared by the PW method were found to have a significantly higher activity in a galactosamine mouse lethality model, in induction of TNF and the Limulus amoebocyte lysate (LAL) assay, than LPS extracted by the PCP or Triton-Mg2+ methods. LPS from Bacteroides strains extracted by the PCP method had consistently low activity in all assays. Comparing PW-LPS from Bacteroides strains with that from E. coli O18:K- in the galactosamine mouse model, the E. coli O18:K- LPS was c. 5000-fold more active than the most active bacteroides LPS. However, in the LAL assay native PW-LPS from both the B. fragilis strains, and B. caccae had higher activities (up to 30 fold) than E. coli O18:K- LPS, with the PW-LPS from the other Bacteroides spp. being up to 15-fold less active than the E. coli O18:K- PW-LPS. In the TNF induction assay, E. coli O18:K- PW-LPS was 4-50-fold more active than bacteroides PW-LPS.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7869346 TI - Phenotypic characterisation of Acinetobacter strains of 13 DNA-DNA hybridisation groups by means of the biolog system. AB - A collection of 129 Acinetobacter strains belonging to DNA groups (genomic species) 1-14 (1-7 and 10-12 sensu Bouvet and Grimont; 8 and 13-14 sensu Tjernberg and Ursing) were investigated for their ability to oxidise 95 carbon sources in the Biolog system. The strain groupings obtained by cluster analysis with the Biolog software were compared with the results of DNA-DNA hybridisation studies. Strains of DNA groups 1 (A. calcoaceticus), 2 (A. baumannii), 3 and 13 were linked in one cluster, as were DNA groups 4 (A. haemolyticus) and 6, DNA groups 10 and 11, and DNA groups 8 (A. lwoffii) and 12 (A. radioresistens). Strains of DNA group 5 (A. junii) were grouped in a single cluster with one strain of DNA group 4. Strains of DNA groups 7 (A. johnsonii) and 14 formed separate clusters. With the exception of the linkage of DNA groups 8 and 12, these results correlated with classification of reference strains of the DNA groups by DNA-DNA hybridisation, but six strains of four different DNA groups were not allocated to the clusters of their respective DNA groups. In the case of DNA groups 4, 5, 6, 7, 10, 11 and 14, at least one carbon source oxidation test could be used to differentiate them from the other DNA groups. PMID- 7869347 TI - Differences exist in the immunoblotting profiles of cyst and trophozoite antigens of Pneumocystis carinii. AB - The antigenic profiles of Pneumocystis carinii trophozoites and cysts were compared by immunoblotting with hyperimmune rat sera against cyst and trophozoite antigens. Strong bands corresponding to proteins of 50-60 kDa and 104 kDa were demonstrated in cyst and trophozoite antigens by all antisera. Additional prominent proteins of 81 and 63 kDa and less prominent proteins of 88, 73, 69 and 37 kDa were found only in trophozoite antigen. The latter proteins were recognised by anti-trophozoite and anti-cyst antisera but the 81- and 63-kDa proteins were associated specifically with trophozoites. With cyst-rich antigen, antibodies to the 50-60-kDa protein were detected in only two of 14 sera from P. carinii pneumonia (PCP)-positive rats. With trophozoite-rich antigen, 11 of 24 rats with PCP and one of 18 PCP-negative animals had antibodies to both the 50-60 kDa and 104-kDa antigens. Antibodies to the 81- or 63-kDa antigens were demonstrated in 15 of 24 PCP-positive animals and none of the PCP-negative animals. The use of trophozoites rather than cysts increased the sensitivity of immunoblotting. As trophozoites predominate in PCP, antibody to trophozoite specific antigens rather than common cyst and trophozoite antigens is likely to be a more useful marker of current infection. PMID- 7869348 TI - Typing of Staphylococcus aureus colonising human nasal carriers by pulsed-field gel electrophoresis. AB - Colonisation by Staphylococcus aureus in the nares of 120 outpatients and 63 healthy adults was studied for c. 2 years. Two states of carriage of S. aureus were confirmed: persistent carriage and persistent non-carriage. The states of carriage and non-carriage were quite stable and > 60% of the population of any of the study groups were stable non-carriers. The results of typing the strains isolated from the same individuals at different times with DNA fingerprinting by digestion with SmaI enzyme showed that all the stable carriers were persistently infected with the same strain and that changes in the strain seldom occurred. PMID- 7869350 TI - Invasive Haemophilus influenzae disease: the impact of Hib immunisation. PMID- 7869349 TI - Brucella abortus causes an accelerated repopulation of the spleen and liver of mice by macrophages after their liposome-mediated depletion. AB - Different macrophage subsets are present in the spleen, i.e., marginal zone macrophages (MZM), marginal metallophilic macrophages (MMM) and red pulp macrophages (RPM) and all are depleted by a single treatment with liposome encapsulated clodronate. These macrophages can be distinguished by differences in localisation patterns, membrane antigens and repopulation kinetics after depletion. In experiments on the involvement of splenic macrophages in the humoral immune response, there was an acceleration of the repopulation kinetics of all macrophage subsets in the spleen after intravenous injection of an autoclaved suspension of Brucella abortus 544 (BA 544 antigen). The time required to obtain 100% repopulation in macrophage-depleted control mice was 2 weeks for RPM, 6 weeks for MMM and > 2 months for MZM. However, after BA 544 injection, 100% repopulation was obtained within 4 days in the case of RPM and within 2 weeks in the case of MMM. Acid phosphatase activity, indicating the presence of MZM, had returned to normal levels within 2 months. Acceleration of repopulation was observed only after intravenous administration of antigen preparations from Brucella strains (except strain BA 19). Although BA 544 antigen stimulated the proliferation of precursors of all of the macrophage subsets in the spleen and liver, it also affected mature members of the mononuclear phagocyte system such as MZM and dendritic cells in the spleen. PMID- 7869351 TI - Clostridial infection in children. AB - A survey of the isolation of Clostridium spp. from 1543 specimens sent to anaerobic microbiology laboratories revealed 113 isolates from 107 specimens (7.0% of all specimens) from 96 children. The isolates comprised 43 (38%) unidentified Clostridium spp., 37 (33%) C. perfringens, 13 (12%) C. ramosum, five (4%) C. innocuum, six (5%) C. botulinum, three (3%) C. difficile, two (2%) C. butyricum, and one isolate each of C. bifermentans, C. clostridiiforme, C. limosum and C. paraputrificum. Most clostridial isolates were from abscesses (38), peritonitis (26), bacteraemia (10), and chronic otitis media (7). Predisposing or underlying conditions were present in 31 (32%) cases. These were immunodeficiency (12), malignancy (9), diabetes (7), trauma (7), presence of a foreign body (6) and previous surgery (6). The clostridia were the only bacterial isolates in 14 (15%) cases; 82 (85%) cases had mixed infection. The species most commonly isolated with clostridia were anaerobic cocci (57); Bacteroides spp. (B. fragilis group) (50), Escherichia coli (22), pigmented Prevotella or Porphyromonas spp. (18) and Fusobacterium spp. (10). Most Bacteroides and Escherichia coli isolates with clostridia were from abdominal infections and skin and soft tissue infections adjacent to the rectal area; most pigmented Prevotella and Porphyromonas isolates were from oropharyngeal, pulmonary, and head and neck sites. Antimicrobial therapy was given to all patients, in conjunction with surgical drainage in 34 (35%). Only two patients died. These data illustrate the importance of Clostridium spp. in paediatric infections. PMID- 7869352 TI - Characterisation of a haemolysin related to Vp-TDH produced by a Kanagawa phenomenon-negative clinical isolate of Vibrio parahaemolyticus. AB - The production of a family of haemolysins--thermostable direct haemolysin (Vp TDH), Vp-TDH-related haemolysin (Vp-TRH) and Vp-TDH/I--has been reported in clinical isolates of Vibrio parahaemolyticus. This paper describes a fourth type of haemolysin--Vp-TDH/II--produced by a Kanagawa phenomenon-negative clinical isolate of V. parahaemolyticus (O13:K, untypable). Vp-TDH/II was purified by ammonium sulphate precipitation and successive filtrations on DEAE-cellulose, hydroxyapatite, Sepharose 4B and Mono Q columns. Vp-TDH/II was biophysicochemically and immunologically similar to, but not identical to Vp-TDH, Vp-TRH and Vp-TDH/I. Vp-TDH/II stimulated vascular permeability in rabbit skin and was lethal to mice. Purified Vp-TDH/II and viable cells of the Vp-TDH/II producing strain both induced fluid accumulation in ligated rabbit intestine. The plasmid-determined structural gene for Vp-TDH/II was cloned and the nucleotide sequence determined. The deduced amino acid sequence of Vp-TDH/II differed from those of Vp-TDH, Vp-TRH and Vp-TDH/I. PMID- 7869353 TI - Superantigenic exotoxin production by isolates of Staphylococcus aureus from the Kawasaki syndrome patients and age-matched control children. AB - Nineteen strains of Staphylococcus aureus were isolated from the throat or the tooth surfaces of 19 cases amongst 127 patients with Kawasaki syndrome (KS) during the acute phases and 11 S. aureus isolates were obtained from five of 17 diseased controls and six healthy controls. The production of exotoxins, particularly superantigenic toxic shock syndrome toxin-1 (TSST-1), coagulase serotype, pigment production, haemolytic activity and tryptophan auxotrophy of these isolates were compared. Among 10 KS S. aureus strains isolated in 1990 1991, five (50%) secreted TSST-1, a higher frequency than two (18%) of 11 control isolates. In contrast, none of the nine KS strains collected in 1984 produced TSST-1. Four of five TSST-1-secreting KS strains produced white or white to golden pigmentation, whereas the two control strains capable of TSST-1 production formed golden colonies. There were no noticeable differences between S. aureus strains from KS patients and control children in the production of staphylococcal exotoxins A-E, coagulase serotype, haemolysis of sheep erythrocytes and tryptophan auxotrophy. The pathological or aetiological role of a new TSST-1 secreting S. aureus clone in patients with KS was not confirmed. PMID- 7869354 TI - Detection by PCR and analysis of the distribution of a fibronectin-binding protein gene (fbn) among staphylococcal isolates. AB - The fibronectin-binding proteins of Staphylococcus aureus are considered to be important virulence factors for colonisation and infection. The polymerase chain reaction (PCR) was used to detect part of a gene equivalent to the fbnA gene of S. aureus in 120 isolates of staphylococci (S. aureus, S. epidermidis, S. haemolyticus, S. simulans, S. hominis, S. warneri, S. cohnii and S. lugdunensis). Primers specific for the binding domain region of the fbnA gene of S. aureus produced PCR products of the predicted sizes (93 and 207 bp). The identity of the PCR products was confirmed by digestion with DdeI and nucleic acid hybridisation. The fibronectin-binding activity of the staphylococci was determined with a particle agglutination assay (PAA). The fbn gene was found to be present by PCR in 107 of the 120 staphylococci tested, irrespective of their site of isolation, and expression of the gene was detected by PAA in 101 of the 120 strains. PMID- 7869355 TI - Histochemical and immunohistochemical similarities between hepatic tumors in two chimpanzees and man. AB - A well-differentiated trabecular hepatocellular carcinoma (HCC) and a well differentiated tumor resembling HCC from each of two chimpanzees were found to have histochemical and immunohistochemical staining characteristics similar to those in human HCCs. Transforming growth factor alpha was overexpressed in both tumors. Oval cells, thought to be liver stem cell progeny with a possible role in hepatocarcinogenesis, were observed among nontumorous hepatocytes, particularly near the tumors. Hepatic tumors are rare in chimpanzees but their similarities to human HCC provides a useful research model. PMID- 7869356 TI - A review of studies of the activation of the blood coagulation mechanism in chimpanzees (Pan troglodytes). AB - This paper reviews our recent studies of blood coagulation activation in the chimpanzee which were carried out employing sensitive immunoassays that measure activation markers of blood coagulation in plasma. Infused factor VIIa activated both factors IX and X in vivo; this reaction depended on the formation of the factor VIIa-tissue factor (TF) complex. The infusion of endotoxin also led to assembly of the factor VIIa-TF complex, enhancing fibrin formation. This process occurred through the intermediate action of specific cytokines. PMID- 7869357 TI - Primate antibodies to components of the human immune system. AB - The feasibility to raise nonhuman primate antibodies against selected components of the human immune system was tested. The immunogens were whole cells (human T lymphocytes) or purified, recombinant human proteins (cytokines: TNF alpha or GM CSF; soluble forms of cell surface antigens: sCD4 or sCD25). Significant immunizations, yielding functionally relevant antibodies, were readily achieved in rhesus monkeys, but, not surprisingly, may be less frequent in chimpanzees. The results suggest a general strategy for production of therapeutically useful MAB. PMID- 7869358 TI - Early helper T-cell dysfunction in simian immunodeficiency virus but not in human immunodeficiency virus type-2-infected macaques. AB - Both naive and vaccinated macaques acquired a virus-specific proliferative helper T-cell reactivity in response to infection with the nonpathogenic human immunodeficiency virus type 2 (HIV-2). In contrast, macaques infected with the pathogenic simian immunodeficiency virus of the macaque strain (SIVmac) did not develop a helper T-cell response. Furthermore, a vaccine-induced preexisting T cell reactivity was abrogated after SIVmac infection in vaccine failures. These differences may reflect the different pathogenicity of the two closely related viruses. PMID- 7869359 TI - Cryptosporidiosis of liver and pancreas in rhesus monkeys with experimental SIV infection. AB - Following an experimental SIV infection, 11 rhesus monkeys were evaluated to determine the presence of opportunistic infections. Five animals had severe alterations of the hepatobiliary tree, three of which were associated with the presence of numerous Cryptosporidium spp. Subacute to chronic inflammatory changes were observed in the pancreatic ducts of four animals, one without histologic evidence of parasites. In one animal, the inflamed ducts were associated with a chronic interstitial pancreatitis. The rate of Cryptosporidium infection together with hepatic and pancreatic involvement (36%) supports the hypothesis that systemic cryptosporidiosis is the result of a loss of protective mucosal immunity. PMID- 7869360 TI - Spontaneous colitis cystica profunda in captive tamarins. AB - Of the 232 tamarins (133 Saguinus mystax and 99 Saguinus labiatus) that died at the Center for Reproduction and Conservation of Nonhuman Primates in Iquitos, Peru from January 1987 to December 1990, 23 monkeys (9.9%) were diagnosed as having chronic colitis. Typically, the cecal and colonic mucosa was greyish and small yellowish cysts, measuring 1-4 mm, were found randomly distributed bulging the mucosa. Microscopically, colitis cystica profunda was diagnosed additionally in six more animals, giving a total of 29 cases (12.5%). This is the first report to our knowledge that describes colitis cystica profunda in a nonhuman primate. PMID- 7869361 TI - Hydranencephaly in two rhesus monkeys (Macaca mulatta). AB - Spontaneously occurring hydranencephaly was diagnosed at necropsy and confirmed histologically in two stillborn fetuses that were delivered from young female rhesus macaques (Maccaca mulatta). PMID- 7869362 TI - Assessment of acrosomal integrity of vervet monkey spermatozoa after cryopreservation. AB - Cryopreservation of Vervet monkey semen caused a highly significant reduction in the percentage of normal acrosomes and a highly significant increase in the percentage of mildly damaged, severely damaged, and lost acrosomes. This was demonstrated by staining ten post-thaw semen samples, which enabled a visualization of the acrosomal damage. The incidence of post-thaw intact acrosomes in this cryopreservation method was found to be similar to that reported for man and cynomolgus monkey semen. PMID- 7869363 TI - Intracellular localization of the antitumour drug adriamycin in living cultured cells: a confocal microscopy study. AB - The intracellular distribution of the anthracyclinic antibiotic adriamycin in living cultured cells has been investigated by confocal microscopy. In human melanoma cells (M14), adriamycin was localized inside the nuclei. When adriamycin treated M14 cells were allowed to recover in drug-free medium, a complete efflux of the drug from the nucleus was revealed. In recovered cells, a weakly fluorescent signal was observed in the perinuclear region. When M14 cells were recovered in a medium containing colcemid, a microtubule depolymerizing agent, the drug transport from the nucleus to the cell periphery appeared to be inhibited, suggesting that the microtubule network is strongly involved in drug transport mechanisms. In multidrug-resistant (MDR) cells the intracellular location of adriamycin was shown to be noticeably different from that of the parental wild-type cells. In particular, in resistant human breast carcinoma cells (MCF-7), adriamycin appeared to be exclusively located within the cytoplasm whereas the nuclei were shown to be completely negative. When adriamycin treatment was performed in association with MDR revertants, such as Lonidamine (inhibitor of the energy metabolism) or verapamil (inhibitor of the P glycoprotein efflux pump), a marked enhancement of the cytoplasmic signal was observed in resistant cells. Under these conditions, adriamycin appeared concentrated in the perinuclear region, but the nuclei were still negative. Confocal microscopy proved to be a very useful method for the study of the intracellular transport of fluorescent substances, such as anthracyclinic antibiotics, and for the investigation of the multidrug resistance phenomenon in tumour cells. PMID- 7869364 TI - Studies of porphyrin-containing specimens using an optical spectrometer connected to a confocal scanning laser microscope. AB - A spectrometer has been developed for use with a confocal scanning laser microscope. With this unit, spectral information from a single point or a user defined region within the microscope specimen can be recorded. A glass prism is used to disperse the spectral components of the recorded light over a linear CCD photodiode array with 256 elements. A regulated cooling unit keeps the detector at 277 K, thereby allowing integration times of up to 60 s. The spectral resolving power, lambda/delta lambda, ranges from 350 at lambda = 400 nm to 100 at lambda = 700 nm. Since the entrance aperture of the spectrometer has the same size as the detector pinhole used during normal confocal scanning, the three dimensional spatial resolution is equivalent to that of normal confocal scanning. Light from the specimen is deflected to the spectrometer by a solenoid controlled mirror, allowing fast and easy switching between normal confocal scanning and spectrometer readings. With this equipment, studies of rodent liver specimens containing porphyrins have been made. The subcellular localization is of interest for the mechanisms of photodynamic therapy (PDT) of malignant tumours. Spectroscopic detection is necessary to distinguish the porphyrin signal from other fluorescent components in the specimen. Two different substances were administered to the tissue, Photofrin, a haematoporphyrin derivative (HPD) and delta-amino levulinic acid (ALA), a precursor to protoporphyrin IX and haem in the haem cycle. Both are substances under clinical trials for PDT of malignant tumours. Following administration of these compounds to the tissue, the potent photosensitizer and fluorescent compound Photofrin, or protoporphyrin IX, respectively, is accumulated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869365 TI - Scanning force microscopy on live cultured cells: imaging and force-versus distance investigations. AB - Extensive measurements with the scanning force microscope on living cells in their native liquid environment are described with the purpose of critically assessing the extent of the interaction between the SFM tip and the (soft) cell materials and the effect of such interaction on topographic information. Images are obtained under various force conditions and systematically correlated with force-versus-distance curves. As a result, detailed indications about tip indentation are given, thickness estimates deduced and identification of submembranous cytoplasmic structures suggested. PMID- 7869366 TI - Imaging in the far-red with electronic light microscopy: requirements and limitations. AB - The acquisition of simultaneous dual confocal images with red and far-red light has both advantages (e.g. lower autofluorescence) and limitations. An understanding of these requisites is necessary to acquire high-quality images and to avoid the misinterpretation of experimental data. The poor detection of far red light mandates a high optical transfer efficiency for the system, thus the transmittance of the objective lens and its axial and lateral chromatic aberration in the far-red are important factors for consideration. This technical note is an attempt to 'demystify' the process of filter set design for confocal microscopy by discussing the considerations that went into the construction of a filter set for use with the reagents cyanine 3.18 (Cy3) and cyanine 5.18 (Cy5), and thus to encourage users to look beyond the multi-purpose designs available commercially. The 568-nm laser line exciting Cy3 is at its emission maximum, which limits the collectable Cy3 fluorescence. High-transmission optical filters with sharp band pass cutoffs are thus desirable for maximum light throughout. Light path mirror efficiency rapidly degrades above 700 nm, but the loss of this portion of the Cy5 emission spectrum is acceptable since the fluorophore is very bright, and these very long wavelengths are also likely to introduce aberration. While resolution is decreased with far-red light, there is also greater penetration and less scattering, and it is thus possible to obtain high-quality images from deeper within the specimen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869367 TI - Simultaneous confocal recording of multiple fluorescent labels with improved channel separation. AB - Confocal microscopes are often used to study specimens labelled with fluorophores. A commonly used method for simultaneous recording of the distribution of multiple fluorophores is to divide the fluorescent light emitted by the specimen into different wavelength regions using dichroic and bandpass filters. These different wavelength regions are then distributed to multiple detectors. However, the broad and overlapping spectra of commonly used fluorophores often result in considerable crosstalk between channels. A new technique, intensity-modulated multiple-beam scanning (IMS) microfluorometry, can be used to reduce this cross-talk substantially. The IMS technique is implemented with two laser beams of different wavelengths, intensity-modulated at different frequencies, which illuminate the specimen simultaneously. The two laser wavelengths predominantly excite one fluorophore each. Fluorescent light from the specimen is divided into two wavelength regions (red and green) which are detected by two photomultiplier tubes. The output signals from the photomultiplier tubes are connected to lock-in amplifiers. The effect of using modulated laser beams, in combination with lock-in amplifiers, is strongly to reduce cross-talk between the channels. The performance of the IMS technique using various types of specimen is compared with the results obtained using the conventional multi-detector method. PMID- 7869369 TI - Physician assistants and Mississippi. PMID- 7869368 TI - Laparoscopic appendectomy: have we found a better way? AB - Laparoscopic appendectomy is an attractive option for the surgical treatment of acute appendicitis. When performed by an experienced laparoscopist, the procedure can be accomplished with little variation in time from the standard open technique, provide a superior cosmetic result, shorter hospital stay and a significant reduction in postoperative pain and length of convalescence. In this study a comparison of 42 open appendectomies and 37 laparoscopic appendectomies was made in regard to age, sex, length of stay, cost of stay, and length of convalescence. PMID- 7869370 TI - The Patient Protection Act. PMID- 7869371 TI - Patient protection. PMID- 7869372 TI - Revamping the component societies. PMID- 7869373 TI - Health care, doctors, and patients. PMID- 7869374 TI - Dr. Bobby Spell receive Golden Arrow Award. PMID- 7869375 TI - Interaction between cisplatin-modified DNA and the HMG boxes of HMG 1: DNase I footprinting and circular dichroism. AB - The interactions between the two boxes A and B of HMG 1 and cis diamminedichloroplatinum(II)-modified DNA containing a single intrastrand cross link at the d(GpG) site were studied by DNase I footprinting and circular dichroism. The DNAase I cleavage patterns of the HMG box-platinated DNA complexes are identical, the two boxes inhibiting the DNase I cutting over at least 15 and 12 nucleotide residues in the platinated strand and the complementary strand, respectively. As judged by circular dichroism, the two boxes have the same alpha helical content (56%) and they induce the same conformational changes in the platinated DNA. PMID- 7869376 TI - Hypercooperativity induced by interface mutations in the phosphofructokinase from Escherichia coli. AB - The saturation of the allosteric phosphofructokinase from Escherichia coli by its substrate fructose-6-phosphate is highly cooperative and seems to occur in an "all-or-none" process at all active sites. This cooperativity measured by the Hill coefficient can still be markedly increased by mutation of a single residue located at a subunit interface, Arg152. X-ray crystallography shows that Arg152 forms an ion-pair with Glu148 within an alpha-helix of one subunit. This ion-pair is close to a symmetry axis and interacts with the ion-pair Glu148-Arg152 of the neighbouring chain across the subunit interface. Mutations of Glu148 affect cooperativity much less than those of Arg152. The substitution of Arg152 by lysine increases the Hill coefficient by two-fold to a value larger than the number of substrate binding sites, which exceeds the maximum cooperativity predicted by the two "classical" models, concerted or sequential, of allosteric regulation. This indicates that the steady-state overall hypercooperativity is (at least partly) of kinetic origin. The hypercooperative mutants of Arg152 also show an enhanced cooperativity in their allosteric inhibition by phospho-enol pyruvate. These results suggest that the allosteric coupling between distant sites involves (1) electrostatic interactions across the subunit interface between residues Glu148 and Arg152 from two adjacent chains, and (2) a relative movement of the alpha-helices containing Glu148 and Arg152 that could propagate and amplify a conformational change between the interface and the active site within each subunit. PMID- 7869377 TI - Magnesium cations are required for the association of U small nuclear ribonucleoproteins and SR proteins with pre-mRNA in 200 S large nuclear ribonucleoprotein particles. AB - In previous studies we have shown that specific nuclear pre-mRNAs and their splicing products, as well as the general population of nuclear poly(A)+ RNA, are found packaged in 200 S large nuclear ribonucleoprotein (lnRNP) particles that represent the splicing machinery in vivo. The lnRNP particles contain all U small nuclear ribonucleoproteins (snRNPs) required for splicing, as well as several proteins including non-snRNP splicing factors. Here we show that upon addition of EDTA to sucrose gradient-fractionated 200 S particles, part of their components (e.g. part of the U snRNPs) are no longer associated with pre-mRNAs, which are now packaged in 70 S particles. This 200 S to 70 S transition makes the pre-mRNA more susceptible to digestion by RNase. The effect of EDTA is reversible, as back addition of Mg2+ results in the reconstitution into 200 S lnRNP particles of: (1) all five snRNPs required for splicing; (2) the SR proteins; and (3) CAD mRNA, as a representative of nuclear RNA polymerase II transcripts. Remarkably, electron microscopy of the reconstituted particles shows a compact structure, 50 nm in diameter, that is indistinguishable from the original undissociated particles. We conclude that Mg2+ is required for the integrity of the 200 S lnRNP particles. PMID- 7869378 TI - Intragenic domains of strand-specific repair in Escherichia coli. AB - Heterogeneity of DNA repair has been observed at different levels of genomic organization, including chromatin domains, expressed genes and DNA strands. If heterogeneity also existed intragenically, it could reveal fine details of the excision repair mechanism in vivo. Here we measure the frequency of UV-induced cyclobutane pyrimidine dimers at individual nucleotides within defined portions of two Escherichia coli genes, lacl and lacZ, at various times after irradiation. Two domains of differential repair rates were apparent, with repair being slow at nucleotides adjacent to the transcription start sites. In lacZ, the domain of faster repair began 32 bases downstream of the transcription start site and required the mfd gene. Since mfd codes for a transcription-repair coupling factor, this transcription-coupled repair system evidently becomes operative downstream of the initiation complex region in vivo. Unexpectedly, however, (1) an mfd mutation reduced repair in the downstream domain even when transcription was at a very low level and (2) induction of lacZ transcription with isopropyl beta-D-thiogalactoside overcame this reduction. Evidently, the Mfd transcription repair coupling factor is required for basal levels of strand-specific repair in this gene, but induced levels of repair are related to transcription through another mechanism. PMID- 7869379 TI - Alignment/phylogeny of the papain superfamily of cysteine proteases. AB - An alignment/phylogeny of the papain superfamily of cysteine proteases was created using an initial structure-based alignment followed by successive iterations of sequence alignment and phylogenetic inference. The iterative approach resulted in significant improvements in the alignment/phylogeny. There were three groups of cysteine proteases that were distantly related and which could be aligned against each other only in the active site regions: the papain group, which included such stereotypical cysteine proteases as cathepsins B, C, H, L and S; and the bleomycin hydrolase and calpain groups. There was one bacterial sequence in each of the bleomycin hydrolase and calpain groups. The former probably arose by lateral gene transfer, the latter possibly by direct evolution from an ancestral protease predating the eukaryote/prokaryote divergence. The phylogeny of the papain group indicated that many families diverged almost simultaneously early during eukaryotic evolution. In mammals there are at least 12 distinct families of cysteine proteases, possibly many more, including at least two as yet uncharacterized enzymes. PMID- 7869380 TI - Structural comparison of cuticle and interstitial collagens from annelids living in shallow sea-water and at deep-sea hydrothermal vents. AB - Two types of annelid collagens of different sizes were purified, one from acetic acid extracts of the cuticle (length 2.5 microns) and the other, after pepsin digestion, from interstitial spaces of the body wall (0.3 micron). They were obtained from Alvinella pompejana, Alvinella caudata and Paralvinella grasslei collected at 2600 m depth around anoxic hydrothermal vents and from Arenicola marina and Nereis diversicolor living in shallow sea-water habitats. The length of the corresponding collagens from different species and their amino acid compositions including the hydroxylation of proline were remarkably similar. The melting point of the triple helix, however, differed between the Alvinella species (approximately 45 degrees C), Paralvinella (approximately 35 degrees C) and the shallow sea-water annelids (approximately 28 degrees C), indicating adaption to habitats with different temperatures. The cuticle collagens of the annelids possess a globular domain, which is apparently involved in oligomer formation, and show similar fragment pattern. Almost identical cross-striation patterns of segment-long-spacing segments of the interstitial collagens indicated sequence similarity, which was confirmed by partial Edman degradation of alpha chains. These data showed almost complete identity between the two Alvinella species and a lower sequence identity with Paralvinella (approximately 95%), Arenicola (67 to 72%) and the vent vestimentiferan Riftia pachyptila (64 to 71%). The data suggest a close evolutionary relationship between these worms, despite a clear separation of habitat preference and thermal stability of the collagens. PMID- 7869381 TI - Contributions of multiple basic amino acids in the C-terminal region of yeast ribosomal protein L1 to 5 S rRNA binding and 60 S ribosome stability. AB - Previous studies suggest that the C-terminal region of ribosomal protein L1 from Saccharomyces cerevisiae is important for its interaction with the 5 S rRNA molecule. Within this region are several highly conserved basic amino acids including Lys276, Lys279, Lys289, Arg282, Arg285. To examine potential contributions of these amino acids to RNA-protein interaction and ribosomal assembly, effects of substitutions of these residues by methionine either individually or in combinations were examined. A methionine substitution of any one of the lysine residues did not significantly affect RNA binding in vitro. The mutant RNPs were as stable as the wild-type RNP. Yeast transformants expressing these mutant proteins grew at the same rate as the wild-type. However, mutant proteins containing substitutions of any two of these basic amino acids bound RNA weakly. The resultant RNPs were significantly less stable than the wild-type. Whereas cells expressing mutant L1 with a single substitution at 289 was not lethal, cells expressing mutant L1 with any double substitutions involving Lys289 as one of the substituted amino acids were lethal. These data suggest that Lys289 plays a key role in the binding of ribosomal protein L1 to 5 S rRNA. The other basic residues, particularly Arg282, and Arg285, in this region also contribute to RNA binding. These residues are predicted to locate on the same side of an alpha helix. We would like to propose a structural model for the yeast RNP that involves multiple contact sites located on one side of the helix in the C terminus of the protein and the 5 S rRNA. These basic amino acids also participate, directly or indirectly, in the interaction of the RNP complex with other components of the 60 S ribosomal subunit. PMID- 7869382 TI - The mechanism of protein crystal growth from lipid layers. AB - Two-dimensional (2D) crystals of proteins on lipid monolayers can initiate the formation of large three-dimensional (3D) crystals suitable for X-ray diffraction studies. The role of the 2D crystals in this process has not been firmly established. While it is likely that the 2D crystals serve as nuclei for epitaxial crystal growth, other mechanisms, such as non-specific nucleation induced by the high local concentration of the protein at the surface of the lipid layer, cannot be excluded. Using streptavidin as a model system, we have now firmly established that 3D crystal growth from 2D crystals on lipid layers occurs by epitaxy. We show that 2D crystals of streptavidin (space group C222) on biotinated lipid layers nucleate the growth of a 3D crystal form (space group I4I22) that possesses a structural similarity with the 2D crystal, but have no effect on the growth of 3D crystal forms (I222 and P2(1)) that are unrelated to the 2D crystal. At lower pH, a new 3D crystal form (space group P1), unrelated to the previously described 2D crystals, grew from lipid layers. This discovery initially raised concern about the validity of the epitaxial mechanism, but these concerns were alleviated with the subsequent discovery of a structurally related 2D P1 crystal that grew in similar solution conditions. Some parameters affecting epitaxial growth of both the P1 and I4I22 crystals were investigated, revealing several noteworthy features of the epitaxial growth. (1) 2D crystals are very effective nucleating agents; for instance, the P1 2D crystals can direct the growth of P1 3D crystals even under conditions that favour the growth of other crystal forms. (2) The epitaxial 3D crystal grow very rapidly and at amazingly low protein concentrations; P1 3D crystals can be grown from solutions as low as 10 microM streptavidin. (3) There is no obligate requirement for the deposition of pre-formed 2D crystals; lipid layers alone are equally effective at promoting epitaxial crystal growth. PMID- 7869383 TI - Alanine scanning mutagenesis of the alpha-helix 115-123 of phage T4 lysozyme: effects on structure, stability and the binding of solvent. AB - A series of individual alanine mutations has been constructed in the helical region 115 to 123 in phage T4 lysozyme in order to evaluate the contribution to protein stability of the different side-chains within this region. Pairwise alanine mutations and a combination mutant with seven alanine substitutions were constructed to evaluate the additive effects upon structure and stability. Only three residues within this region (Ser117, Leu118 and Leu121) have a substantial influence upon stability (change in free energy of unfolding greater than 1.0 kcal/mol). Replacement of Ser117 with alanine results in an increase in protein stability of 1.27 kcal/mol, apparently due to the release of strain present in the wild-type protein. Replacement of the buried residues Leu118 and Leu121 is destabilizing. Substitution of the remaining six residues with alanine has relatively little effect on stability. This is consistent with prior studies showing that only 20 to 30% of the residues in amphipathic helices in T4 lysozyme are critical for stability. For some of the pairwise alanine mutants the effects on stability are additive. For most of these mutants, however, there is a slight (approximately 0.15 to 0.25 kcal/mol) non-additivity such that the double mutant is more stable than the sum of the constituent single mutants. This effect is consistently observed for residues with positions i, i +4; i.e. adjacent, but in consecutive turns of the helix, suggesting a weak but significant interaction between these amino acid residues. A more pronounced non-additivity (approximately 0.5 kcal/mol) is seen in the seven-alanine combination mutant. This non-additivity is due to a modest "collapse" or "repacking" that occurs for the combination mutants (especially the multiple alanine mutant) but is not possible for the single replacements. The truncation of some side-chains permits an increase in solvent accessibility of main-chain amide and carbonyl groups. This effect is most pronounced for the seven-alanine combination mutant, where two solvent molecules, not present in wild-type, hydrogen bond to main-chain carbonyl groups in the middle region of the helix. It has been suggested that the binding of such water molecules might represent the first step in solvent mediated unfolding of an alpha-helix. The appearance of ordered solvent, however, appears to have very little effect on stability (approximately less than 0.2 kcal/mol). PMID- 7869384 TI - The three-dimensional solution structure of human stefin A. AB - The three-dimensional solution structure of recombinant human stefin A has been determined by a simulated annealing protocol using a total of 1113 distance and angle constraints obtained from 1H and 15N HMR spectroscopy. The solution structure is represented by a family of 17 conformers with an average root-mean square deviation relative to the mean structure of 0.44 A for backbone atoms and 0.94 A for all heavy atoms for the main body of the structure. The protein has a well-defined global fold consisting of five anti-parallel beta-strands wrapped around a central five-turn alpha-helix. There is considerable similarity between the structural features of free stefin A in solution and the X-ray structure of the homologous protein stefin B in its complex with papain, but there are also some important differences in the regions which are fundamental to proteinase binding. The differences consist primarily of two regions of high conformational heterogeneity in free stefin A which correspond in stefin B to two of the components of the tripartite wedge that docks into the active site of the target proteinase. These regions, which are shown to be mobile in solution, are the five N-terminal residues and the second binding loop. In the bound conformation of stefin B they form a turn and a short helix, respectively. PMID- 7869385 TI - Diversification of brain morphology in antarctic notothenioid fishes: basic descriptions and ecological considerations. AB - The Notothenioidei, a perciform suborder of 120 species, dominates the ichthyofauna of the Southern Ocean around Antarctica. Unlike most teleost groups, notothenioids have undergone a corresponding ecological and phyletic diversification and therefore provide an excellent opportunity to study the divergence of the nervous system in an unusual environment. Our goal is to evaluate notothenioid brain variation in light of this diversification. To provide a baseline morphology, we examine the gross morphology and histology of the brain of Trematomus bernacchii, a generalized member of the family Nototheniidae. We then examine the variation in brain gross anatomy (32 species) and histology (10 species) of other notothenioids. Our sample represents about 27% of the species in this group and includes species from each of the six families, as well as species representing diverse ecologies. For comparison we reference the well-studied brains of two species of temperate perciformes (Perca flavescens and Lepomis humilis). Our results show that, in general, notothenioid brains are more similar to the brains of temperate perciforms than to the unusual brains of cave-dwelling and deep-sea fishes. Interspecific variation in gross brain morphology is comparable to that in Old World cyprinids and is illustrated for 17 species. Variation is especially noteworthy in the ecologically and geographically diverse family Nototheniidae. Measurements indicate that sensory regions (olfactory bulbs, eminentia granularis, and crista cerebellaris) exhibit the most pronounced variation in relative surface area. Association areas, including the corpus cerebelli and the telencephalon, exhibit moderate variation in size, shape, and lobation patterns. Regulatory areas of the brain, including the saccus vasculosus and the subependyma of the third ventricle, are also variable. These regions are best developed in species living in the subfreezing water close to the continent. In some species the expanded ependymal lining forms ventricular sacs, not previously described in any other vertebrate. Three species, including two nototheniids (Eleginops maclovinus and Pleuragramma antarcticum) and the only artedidraconid in our sample, have distinctive brains. The unique brain morphology of Pleuragramma is probably related to a sensory (lateral line) specialization for feeding. Within the Nototheniidae, a phyletic effect on cerebellar morphology is evident in the Coriiceps group and in the Pleuragramminae. Neither phyletic position nor ecological factors (water temperature, position in the water column, dietary habits) alone fully explain the pattern of notothenioid brain diversification. PMID- 7869386 TI - Morphology of the abdominal wall in the bat, Pteronotus parnellii (Microchiroptera: Mormoopidae): implications for biosonar vocalization. AB - We investigated the structure of the abdominal wall of Pteronotus parnellii and made comparisons with eight other species of Microchiroptera and one megachiropteran. Similar to other mammals, the abdominal wall of bats consists of the three flank muscles laterally and the m. rectus abdominis ventrally. In Microchiroptera, flank muscles are mostly confined to dorsal portions of the wall. The mm. transversus abdominis and obliquus internus abdominis form the bulk of the wall; the m. obliquus externus is poorly developed. Ventrolaterally, a large portion of the wall is a dense, bilaminar aponeurosis, composed of collagen, elastin, and fibroblasts. The thicker, superficial lamina derives from the mm. obliquus internus and transversus abdominis. The deep lamina is a continuation of the transversalis fascia. Collagen fibers of the two fused laminae are oriented orthogonally, resulting in a resilient, composite fabric. Fascicles of the flank muscles are oriented along the margins of the aponeurosis so that their forces appear to be concentrated onto the aponeurosis. We suggest that this system is adapted for the regulation and generation of intra-abdominal pressure. The abdominal wall of Pteropus, the one megachiropteran examined, lacks the derived aponeurosis and is similar to other mammals. We consider the abdominal wall of Microchiroptera to be analogous to the diaphragma, in that it functions in the regulation of pressure within body cavities and facilitates biosonar vocalization. PMID- 7869387 TI - Reduced ryanodine receptor content in isolated neonatal cardiomyocytes compared with the intact tissue. AB - The effects of isolation and culture of rat neonatal ventricular myocytes on the properties of the ryanodine receptor were investigated. [3H]-Ryanodine bound to a single class of sites in membranes prepared from intact neonatal ventricle, with an affinity of 16.3 +/- 2.8 nm (mean +/- S.E.; n = 3) and a capacity of 546 +/- 64 fmol/mg protein (mean +/- S.E.; n = 3). In contrast, no detectable displaceable binding of [3H]-ryanodine was observed when similar experiments were performed using membranes prepared from isolated neonatal cardiomyocytes. The apparent absence of [3H]-ryanodine binding in the neonatal cardiomyocytes suggested either reduced ryanodine receptor protein or the conversion of the receptors to a low affinity state. To distinguish between these possibilities, the content of ryanodine receptor protein was measured using SDS-PAGE followed by western blotting. Membranes prepared from neonatal ventricle contained substantial amounts of ryanodine receptor, as demonstrated by a dense band on western blots. However the corresponding band in preparations of isolated cells, while having similar electrophoretic mobility, was barely detectable. It is concluded that the ryanodine receptor protein is strongly expressed in intact neonatal ventricle, but the level of expression is markedly reduced upon isolation of the cardiomyocytes. These findings demonstrate that ryanodine receptor expression is significantly down-regulated when rat neonatal ventricular myocytes are isolated and maintained in culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869388 TI - Endomyocardial biopsies: a new approach for studying the electrical and mechanical properties of human ventricular myocardium. AB - The novel endomyocardial biopsy approach described here could facilitate the study of some human pathologies for which tissue specimens are currently unavailable. Electrical and mechanical characteristics such as rat responses, effect of extracellular calcium concentration changes and beta-adrenergic tone were similar to those determined for other human ventricular tissues, indicating that endomyocardial biopsies are suitable for physiological studies. This new source of cardiac tissues should facilitate the investigation of cellular mechanisms involved in the development of previously inaccessible human diseases. PMID- 7869389 TI - Sphingosine effects on the contractile behavior of skinned cardiac myocytes. AB - Sphingosine modulates myocyte beating behavior by acting on the sarcoplasmic reticulum calcium release channel, the ryanodine receptor. Chemically skinned myocytes isolated from adult rabbit ventricles exhibited spontaneous asynchonous contractions in response to micromolar levels of calcium. These cells do not have a functional sarcolemma but exhibit spontaneous contraction-relaxation cycles which are controlled by the sarcoplasmic reticulum. The intracellular second messenger, sphingosine, significantly reduced myocyte beat frequency in a biphasic manner with an IC50 of c. 0.5 microM. A computerized video-enhancement micrography system was used to determine the effect of sphingosine on sarcomere contractile parameters and to determine the potential source of the altered beating behavior produced by sphingosine. Contraction parameters related to sarcomere shortening were unaffected by sphingosine in the submicromolar range, suggesting that sphingosine had no effect on the contractile machinery itself. However, submicromolar sphingosine had a significant inhibitory effect on the spread of activation from sarcomere to sarcomere in these cells. Activation waves were propagated with an average velocity of 331 and 199 microns/s in control and sphingosine (0.58 microM) treated cells, respectively. Permeabilized myocyte calcium uptake was markedly increased by treatment with sphingosine, consistent with an inhibitory effect of sphingosine on sarcoplasmic reticulum calcium release. Sphingosine blocked calcium-induced calcium release from isolated cardiac sarcoplasmic reticulum membranes containing the ryanodine receptor. The results suggest that the site of sphingosine action on calcium signaling and beating behavior in the cardiac cell is the sarcoplasmic reticulum ryanodine receptor. By inhibiting channel opening sphingosine may increase the calcium threshold necessary to trigger calcium-induced calcium release, thus modulating cardiac excitation-contraction coupling. PMID- 7869390 TI - Altered expression of titin and contractile proteins in failing human myocardium. AB - Our own previous ultrastructural studies in human hearts with dilated cardiomyopathy and heart failure showed sarcomeric and cytoskeletal disarrangement. On the basis of these findings we tested the hypothesis that in cardiomyopathic failing hearts not only the sarcomere structure but also the organization and the amount of numerous contractile proteins are disturbed. Titin was included in this study because it is the elastic "third" filament of the sarcomere and also plays an important role as template for myosin and actin filaments in sarcomerogenesis. Human cardiac tissue obtained at the time of transplantation surgery was investigated using immunohistochemistry with monoclonal antibodies against titin, myosin, actin, tropomyosin, and troponin T. Additionally, isolated myocytes from rat or pig heart were used for the standardization of the localization pattern. In normal tissue, myosin and the thin filament complex showed a regular cross striation that was wider in myosin staining than for actin, troponin T, and tropomyosin corresponding with the different width of the A and I bands in the sarcomere. Titin localization in normal human and animal myocardium showed a regular cross striation pattern. In diseased cardiac tissue titin fluorescence intensity was reduced and frequently disorganization or almost complete loss of titin from many myocytes were present. Severe abnormalities of contractile proteins consisting of disarrangement or lack of filaments were also observed. Double staining procedures showed that in the same myocyte defects of the contractile apparatus were accompanied by a simultaneous reduction of titin indicating that the "third" sarcomeric filament system is involved in heart failure. Abnormalities of titin expression may be especially important because titin significantly influences sarcomeric elastic behaviour and is necessary as template for the organization of newly synthesized myosin and actin filaments. The loss of titin may contribute to the altered compliance in failing hearts. It is concluded that disorganization and loss of titin, myosin, and the thin filament complex are severe in the failing human heart because of dilated cardiomyopathy and that these changes may represent several of the most important components of the structural correlate of reduced cardiac function. PMID- 7869392 TI - Cardiac noradrenaline release accelerates adenosine formation in the ischemic rat heart: role of neuronal noradrenaline carrier and adrenergic receptors. AB - In the present study the hypothesis was tested that local noradrenaline release contributes to adenosine formation in myocardial ischemia. Therefore, in ischemic non-working rat hearts either adrenergic receptors or ischemia-evoked noradrenaline release were blocked. Noradrenaline and adenosine were determined in the effluent using HPLC-methods. Following 20 min of stop of perfusion flow both the beta-adrenergic receptor antagonist bisoprolol (91.6 +/- 10.5 nmol/g) and the inhibitor of ischemia-induced noradrenaline release desipramine (108.5 +/ 12.5 nmol/g) caused a suppression of adenosine release (control: 140.9 +/- 7.3 nmol/g). To examine the time-course of the release, further experiments were performed at constant perfusion flow with energy metabolism blocked by cyanide together with removal of glucose from the perfusion buffer. This condition resulted in a nearly simultaneous release of adenosine and noradrenaline from the hearts. The beta-adrenoceptor blocking agents atenolol and bisoprolol postponed the release of adenosine, whereas the alpha-antagonists prazosin and yohimbine had no effect on adenosine release induced by cyanide. None of the adrenergic receptor blockers affected the release of noradrenaline. The inhibitors of the neuronal noradrenaline carrier (uptake1) desipramine, oxaprotiline, and cocaine suppressed the release of noradrenaline during cyanide administration, indicating a carrier-mediated efflux of noradrenaline. Reduction of extracellular noradrenaline by these agents coincided with a delay of adenosine release (cumulative release within 20 min--control: 251.2 +/- 13.9, desipramine: 172.1 +/ 15.3, oxaprotiline 36.5 +/- 5.8, cocaine: 111.8 +/- 23.6 nmol/g). Desipramine and cocaine were also used during administration of exogenous noradrenaline in normoxic hearts, to confirm specificity of their action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869391 TI - L-type calcium currents of human myocytes from ventricle of non-failing and failing hearts and from atrium. AB - L-type calcium currents were studied in ventricular myocytes isolated from non failing hearts, i.e. donor hearts not suitable for transplantation, and from severely failing hearts, i.e. explanted hearts of organ recipients, in order to identify possible alterations of the currents in cardiomyopathy. Human atrial myocytes were investigated for comparative purposes. As deficient production of cyclic AMP might contribute to the development of cardiac failure, the responses to forskolin, a direct stimulator of adenylyl cyclase, were also studied. The patch-clamp technique was applied in the single electrode whole-cell mode. Calcium currents were similar in myocytes from non-failing and failing hearts: Maximum current-densities were 3.8 v 3.1 pA/pF, and 2.2 pA/pF in atrial cells. In human ventricular cells, threshold was at -33 mV, maximum at +6 mV and reversal potential at about +50 mV, potentials of half-maximum steady-state inactivation 24 mV and -18 mV. The slopes of steady-state inactivation curves were +4.1 mV in myopathic and +5.5 mV in non-failing cells. In all myocytes the current inactivated with two time constants, a fast one with weak and a slow one with pronounced potential dependency. Ventricular or atrial myocytes from patients pretreated with calcium antagonists and untreated did not differ in current density or steady-state inactivation. Forskolin (0.5 microM) increased calcium currents in myocytes from non-failing and failing hearts to the same extent (by 143 and 150%). While beta-adrenoceptor numbers are reported to decline in severely failing myocardium, our data do not suggest that alterations of the properties of calcium currents contribute to the pathophysiology of heart failure, though the number of investigated hearts is limited due to restricted access to non-failing cardiac tissue. No evidence for impairment of the signal transduction cascade beyond the level of GTP binding proteins was found. PMID- 7869394 TI - Na-Ca exchange is required for rest-decay but not for rest-potentiation of twitches in rabbit and rat ventricular myocytes. AB - The influence of the Na-Ca exchange (NaCaX) on the effects of rest (30-300 s) on twitch amplitude and SR Ca content (assessed by caffeine contractures) was studied in ventricular myocytes isolated from rat and rabbit. In control conditions, rabbit cells showed monotonic rest-decay of the amplitudes of both twitch and caffeine contractures, while rat myocytes developed rest-potentiation of twitches without change in SR Ca content. Inhibition of the Na-Ca exchange during rest by perfusion with 0Na,0Ca solution did not affect the responses in rat cells but abolished rest-dependent SR Ca loss in rabbit cells. Indeed, when NaCaX was blocked during rest, then rabbit cells, like rat, displayed rest potentiation of twitches. Stimulation of net Ca extrusion via NaCaX during rest by perfusion with 0Ca solution induced rest-decay of twitches and caffeine contractures in rat cells similar to that observed in rabbit cells. This maneuver also accelerated decline in SR Ca during rest and amplitude of the first post rest twitch in rabbit myocytes. These effects were only slightly enhanced by preperfusion with 0Na,0Ca solution to deplete Nai. We were thus able to interconvert the contractile responses to rest between these cell types solely by modifying the driving force for Ca transport by the exchange. Our results indicate that SR Ca is lost during quiescence in both species, but only if the NaCaX is able to promote diastolic Ca extrusion will net decline of SR Ca (and twitch amplitude) occur. On the other hand, post-rest twitch potentiation in both rat and rabbit cells can occur without a change in SR Ca content. This effects might be attributable, at least in part, to a slow phase of recovery of excitation-contraction coupling. PMID- 7869393 TI - Single pass sequencing of a unidirectional human fetal heart cDNA library to discover novel genes of the cardiovascular system. AB - A human fetal heart cDNA library was constructed in the lambda gt22A expression vector. Polymerase chain reaction (PCR) was used to amplify the cDNA inserts. PCR products were purified and used in cycle sequencing reactions in the presence of a fluorescein-conjugated primer and electrophoresed on a Pharmacia A.L.F. Sequencer. Partial cDNA sequences, or expressed sequence tags (ESTs) were searched against the Genbank and EMBL databases to identify novel genes expressed in the human cardiovascular system. PMID- 7869395 TI - Prevention of extracellular K+ inhomogeneity across the ischemic border by coronary venous obstruction in the dog: salutary antiarrhythmic effects of enhanced myocardial hydration. AB - Partial coronary sinus obstruction (CSO) in the dog prevents or delays the predictable ventricular fibrillation (VF) of the early phase of acute ischemia, by normalizing regional electrophysiological disparities which presumably reflect inhomogeneous extracellular potassium ([K+]o) accumulation. To clarify whether CSO indeed affects [K+]o inhomogeneity, we determined in 12 chloralose anesthetized dogs the dynamic [K+]o changes occurring early during reversible coronary artery occlusion (CAO) involving the mid-left anterior descending branch. These changes were compared to those observed during CAO preceded by CSO sufficient to increase the coronary sinus pressure to 40 mmHg. [K+]o was determined using valinomycin coated electrodes implanted within the ischemic (IZ) and the normal (NZ) zones, as well as immediately inside (BZi) and outside (BZo) the visible border. [K+]o increased rapidly within the IZ and the BZi reaching plateau 5 min after CAO, at about three-fold control (11.89 +/- 1.12 mEq/l). Unexpectedly, [K+]o also increased initially outside the border (BZo) but declined after 3 min to a lower level (7.00 +/- 0.40 mEq/l), thus creating a steep gradient of up to 5.54 +/- 0.20 mEq/l, P < 0.001) across the visible border. In four trials, the gradient coincided with VF. With CSO preceding CAO, the development of this border zone gradient was entirely prevented. Moreover, [K+]o reached a significantly lower and similar level in the IZ, BZi and BZo (9.5 +/- 0.89 mEq/l, P < 0.001) and no VF was observed. Thus the beneficial electrophysiologic and antiarrhythmic effects of CSO in acute ischemia may be explained by [K+]o equalization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869396 TI - Metabolism of toad ventricle during alterations to the inotropic state. AB - The heat produced by toad ventricle during manipulations of the inotropic state was measured using thermopiles, and some comparisons made to rat ventricle. The tension-independent heat, peak stress, and the tension-dependent heat increased when [Ca2+]o increased from 0.25 to 2 mM in Ringer. In 2 mM [Ca2+]o, tension independent heat, peak stress, and tension-dependent heat were 3.1 +/- 0.4 mJ/g, 38.4 +/- 5.5 mN/mm2, and 0.49 +/- 0.06 units; about 25% of the tension independent heat may relate to the Na(+)-K+ pump. At similar [Ca2+]o, rat ventricle produced a smaller tension-independent heat (1.6 +/- 0.2 mJ/g), and active heat per unit stress (0.22 +/- 0.01 units) than toad. Tension-independent heat, stress, and tension-dependent heat were increased by orciprenaline, and decreased by BDM. Ouabain increased the stress and tension-dependent heat but not the tension-independent heat. Five millimolar [Ca2+]o in HEPES buffer decreased the stress but increased the tension-dependent heat compared to 2 mM [Ca2+]o in Ringer. Ryanodine and CPA caused major reductions in force and tension independent heat in rat, but had little effect on toad ventricle. In conclusion, our results suggest that in toad ventricle (a) the sarcoplasmic reticulum plays only a minor role in activation and relaxation, (b) the Na(+)-K+ pump contributes substantially to activation metabolism, (c) active metabolism is stimulated by increases in [Ca2+]o and (d) there is a larger tension-independent heat, a larger active metabolism per unit stress, and a lower basal metabolism than in rat papillary muscle. The energy cost of removing intracellular Ca2+ through the sarcolemma appears to be greater than uptake into sarcoplasmic reticulum. PMID- 7869397 TI - Altered glucose and fatty acid oxidation in hearts of the spontaneously hypertensive rat. AB - Metabolic fuel oxidation may be altered in left ventricular hypertrophy (LVH), but detailed characterizations are lacking. Although the spontaneously hypertensive rat (SHR) is a widely used experimental model of LVH, its myocardial fuel oxidation rates are unknown. The purpose of this study was to directly measure glucose and fatty acid (FA) oxidation in the SHR heart ex vivo under controlled loading conditions. Hearts from 15-week-old SHR and Sprague Dawley (SD) rats were perfused in a recirculating system and indices of cardiac performance were continuously monitored. The oxidation of glucose and palmitate were determined simultaneously at low and high workloads by the addition of U-14C glucose and 9,10-3H-palmitate to the recirculating perfusate. The results demonstrate that FA oxidation of SHR hearts is profoundly suppressed (60-80%) relative to that of the normotensive SD strain, particularly at high workloads. Glucose oxidation is also moderately elevated, yielding a marked (four-to-five fold) increase in the ratio of glucose/FA oxidation rates in the SHR hearts. Since more ATP is generated per mole of oxygen consumed when glucose is the fuel scource, these results are consistent with the hypothesis that a shift away from FA use toward glucose contributes to the preservation of energetic economy in stable, concentric LVH. PMID- 7869398 TI - Relationships between cytosolic [ATP], [ATP]/[ADP] and ionic fluxes in the perfused rat heart: A 31P, 23Na and 87Rb NMR study. AB - In order to assess the relationship between cytosolic [ATP] or [ATP]/[ADP] and the intracellular Na+ concentration ([Na+]i), we have used the phosphate trap 2 deoxy-D-glucose (DG) to alter the high energy phosphate levels in rat cardiomyocytes. Pyruvate-perfused rat hearts were treated with 2 mM DG in the presence of 10IU/l of insulin for 28 min, followed by perfusion with DG without insulin for 60 min. The DG + insulin treatment resulted in dramatic changes in the 31P NMR spectra: phosphocreatine (PCr) and total ATP decreased (to 15 and 35%, respectively) and deoxyglucose-6-phosphate accumulated, with little change in either inorganic phosphate or intracellular pH. These changes corresponded to a decrease in cytoplasmic [ATP] (from 7.6 to 1.8 mM), [ATP]/[ADP] (from 494 to 24) and ATP affinity [A(ATP), by 8.9 kJ/mol] and an increase in [ADP] (five-fold) and free [Mg2+] (two-fold). Subsequent perfusion with DG--insulin resulted in slow recovery of PCr, [ATP]/[ADP] and A(ATP) such that the "low energy" state lasted an additional 16 min during which ATP remained low and constant. There were no detectable changes in the intracellular Na+ content as assessed by shift reagent-aided 23Na NMR at the end of DG + insulin treatment (98 +/- 18%, 28-36 min of the protocol). In addition, there was no change in the Rb+ influx rate as measured by 87Rb NMR at the beginning of insulin washout which was achieved by replacing 20% of the KCl with RbCl ([K+] = 3.76 mM, [Rb+] = 0.94 mM). During DG + insulin treatment the pressure-rate product (PRP) decreased by half and was restored upon insulin washout to 80% of its initial value both in the presence and in the absence of the shift reagent [5 mM Dy (triethylenetetraminehexaacetate)3-]. These data imply that unfavorable thermodynamic [low A(ATP)] and kinetic (low [ATP] and [ATP]/[ADP]) conditions induced by DG treatment do not inhibit Na+, K(+)-ATPase activity. We speculate that during anoxia when changes in [ATP]/[ADP] are comparable to those induced by DG treatment, the observed increase in [Na+]i is not due to inhibition of the Na+ pump by reduced [ATP] or [ATP]/[ADP]. PMID- 7869399 TI - Tissue restricted gene expression assayed by direct DNA injection into cardiac and skeletal muscle. AB - We have used direct injection of plasmid DNA into heart and tongue in vivo and transfection into cells in culture to determine (1) whether the pattern of reporter gene expression parallels the cell-type specific expression of endogenous genes, (2) whether the pattern of reporter gene expression approximates that of the same constructs transfected into myocardiocytes and myogenic cells in culture, (3) whether the expression patterns of promoters and enhancers that had been subtly altered by mutations are similar following transfection and direct DNA injection. We utilized reporter gene constructs derived from the two fiber-type specific human troponin C genes: the fast twitch gene (TnCf) and the slow twitch or cardiac gene (cTnC). The endogenous TnCf gene does not express in the heart and the plasmid DNA expresses neither in myocardium after injection nor in transfected cardiomyocytes. However injected TnCf does express vigorously in tongue muscle. Conversely, the endogenous cTnC gene does not express in fast twitch skeletal muscles like tongue and the plasmid DNA does not express in tongue after injection. However, injected cTnC does express in both injected myocardium and in transfected cardiomyocytes. With few discrepancies, various deletions and alterations of the promoters and enhancers of these genes that have previously been defined by transfection into permissive myogenic cells in culture gave parallel expression patterns after injection in myocardium and tongue. Thus we conclude that direct DNA injection appears to provide a method to verify the identities of important cis-acting regulatory regions that have been mapped in cells in culture. PMID- 7869400 TI - Adenosine and dipyridamole mimic the effects of ischemic preconditioning. AB - The effects of preconditioning, adenosine and dipyridamole in protecting the systolic and diastolic alterations of myocardial stunning in rabbit hearts were studied. Isovolumic left ventricular developed pressure (LVDP), and end diastolic pressure (LVEDP) were measured. The time constant of relaxation (T) was calculated. Isolated rabbit hearts were subject to 15 min of global ischemia (37 degrees C) followed by 30 min of reperfusion. LVDP and LVEDP stabilized to 55 +/- 5% and 320 +/- 28% of control values respectively (stunned group) T increased early in reperfusion (from 48.2 +/- 3.9 to 97.2 +/- 10 ms P < 0.05) but returned to control value late in reperfusion. When hearts were preconditioned by a single cycle of 5 min of ischemia LVDP and LVEDP stabilized at 89 +/- 3% and 162 +/- 34% of preischemic values respectively (P < 0.05 with respect to stunned group). The change in T was attenuated (62 +/- 6 ms at 5 min of reperfusion, P < 0.05 with respect to stunned group). Hearts treated either with adenosine (800 micrograms/min) or the nucleoside transport blocker dipyridamole (4 micrograms/min) previously to the ischemia, recovered their LVDP to 86 +/- 1% and 82 +/- 3% of preischemic values, respectively (P < 0.05 with respect to stunned group). Adenosine and dipyridamole also attenuated the increase in LVEDP (195 +/- 12% and 197 +/- 10% respectively, P < 0.05 with respect to stunned group).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869401 TI - Research, prevention, and quality assurance in traumatic brain injury: a public hospital perspective. AB - The following recommendations are made: increased Medicaid reimbursement for head injury patients to public hospitals that provide care to disproportionately large numbers of these unemployed, uninsured patients, develop comprehensive federal control legislation concerning gun control, develop violence prevention programs such as curricula to combine public health and criminal justice approach, develop trauma registry for neurologic injuries (brain and spinal cord), enforce the use of seat belts and cycle helmets, develop practice guidelines for traumatic brain injured patients, continue research into the mechanisms and management of brain swelling, neuronal regrowth and transplantations, and other mechanisms to overcome neurologic deficits as well as continue research on post-traumatic syndrome, which results from minor head injuries yet causes significant morbidity and costs, and establish comprehensive rehabilitation and habilitation programs to include physical, cognitive, and behavioral approaches and support systems (eg, "halfway house"). PMID- 7869402 TI - Compliance with public sector HIV medical care. AB - Despite the availability of free or low-cost public sector human immunodeficiency virus (HIV) health-care services, important inequities in utilization exist. This study examined two measures of compliance with HIV medical care: attendance of scheduled outpatient visits and use of the emergency room. Clients of two public HIV outpatient clinics were followed from time of health-care initiation to either death or the end of the study. The association of race, sex, age, and injection drug use (IDU) with these measures were examined in multivariate logistic regression. Models were adjusted for disease staging at time of entry and for length of follow-up time in clinic. Of 1824 clients followed, 15% failed to attend scheduled visits and 18.1% had at least one emergency room visit. Clients who missed visits were more likely to be African American, to have a history of IDU, and to have a CD4 cell count < 500/mm3 or an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection at entry. They were also more likely to have > or = 12 months of follow-up time in the HIV clinic, but were less likely to have entered into health care from an early intervention clinic. Clients who had at least one emergency room visit were more likely to be African American, female, IDU, and under 22 years of age; these clients were also more likely to have entered with CD4 < 200/mm3 or with an opportunistic infection, and to have > or = 12 months of follow-up in the clinic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869403 TI - The value of HIDA scans in the initial evaluation of patients for cholecystitis. AB - One hundred twenty-two consecutive patients who had hepato-iminodiacetic acid (HIDA) scans over a 5-month period were reviewed. These scans were found to have 94% sensitivity, but only 36% specificity for correctly diagnosing pathological variants of cholecystitis. Frequently, HIDA scans were misinterpreted to show common bile duct obstruction (CBDO); only 20% of cases of CBDO suggested on HIDA could be confirmed surgically. Sonography gave 88% to 90% sensitivity and 91% specificity in correctly diagnosing pathological variants of cholecystitis and correctly demonstrated CBDO in 80% of the cases. As first-line studies to evaluate biliary tract disease, HIDA scans are costly and should be eliminated. PMID- 7869404 TI - Controversies in the management of retroperitoneal hemorrhage associated with pelvic fractures. AB - Pelvic fractures present major therapeutic challenge requiring systematic diagnostic and management strategies. This article describes a 50-year-old female with a massive pelvic fracture after being crushed under the wheels of a bus. All aspects of her management are presented in detail. The current indications and role of exploratory laparotomy, internal and external fixation, and diagnostic and therapeutic angiography are discussed. PMID- 7869405 TI - Cancer prevention behaviors among African-American adults: a survey of wards 7 and 8 in Washington, DC. AB - A telephone survey of knowledge, attitude, and health practices regarding cancer was undertaken in wards 7 and 8, Washington, DC in 1988. These wards have the highest cancer rates in the city and are predominantly African American. Of the 670 randomly selected persons over 18 years of age, 243 were males and 427 were females. Among females, 84% believed cigarette smoking causes cancer, and 48% thought alcohol causes cancer; 31% smoked cigarettes and 38% consumed alcoholic beverages. Among males, 91% and 52% thought cigarettes and alcohol causes cancer respectively; 41% smoked and 54% consumed alcoholic beverages. Only 6% of the males over age 40 practiced all eight recommended cancer prevention behaviors, while 2% of the females over age 40 practiced all preventive health behaviors. Cancer preventive behavior was examined in relation to socioeconomic status. This study indicates that preventive health behaviors were not associated with socioeconomic status. Data suggest that cancer prevention and control programs and services targeted to this Washington, DC population should be increased and intensified. PMID- 7869406 TI - Fears in African-American sibling and nonsibling pairs. AB - Research on the familial relationship of fears among African Americans appears to be non-existent. This study examines the familial relationship of fears among African-American children. Twenty-four African-American sibling pairs ages 6 to 12 years were administered the Revised Fear Survey Schedule for Children. Twenty four African-American nonsibling pairs matched on age and sex served as controls. Results partially support the hypothesis that a familial relationship exists for African-American children's fears. PMID- 7869407 TI - Economic issues for African-American surgical specialists in solo or group practices. AB - This clinical research plan was designed to evaluate the predictable and current developments, growth, and stability of the economic status of part-time or full time African-American practicing surgeons. In many communities throughout the United States, the economic successes of certified or experienced black surgical specialists are inhibited or modified by mistrust, jealousy, professional disengagements, prejudices, and self-hatred by black and white physicians and lay African Americans. Nevertheless, there are subtle and overt evidences of increasing satisfactory and above average associative interprofessional relationships between African-American physicians and surgical specialists. One hundred African-American surgical specialists from thirty-four communities in the United States were interviewed at periodic intervals over a period of three decades. Recommendations for improvements and changes are presented. PMID- 7869408 TI - The Tuskegee Syphilis Experiment: biotechnology and the administrative state. AB - The central issue of the Tuskegee Syphilis Experiment was property: property in the body and intellectual property. Once removed from the body, tissue and body fluids were not legally the property of the Tuskegee subjects. Consequently, there was not a direct relationship between a patient and research that used his sera. The Public Health Service (PHS) was free to exercise its property right in Tuskegee sera to develop serologic tests for syphilis with commercial potential. To camouflage the true meaning, the PHS made a distinction between direct clinical studies and indirect studies of tissue and body fluids. This deception caused all reviews to date to limit their examination to documents labeled by the PHS as directly related to the Tuskegee Syphilis Experiment. This excluded other information in the public domain. Despite the absence of a clinical protocol, this subterfuge led each to falsely conclude that the Tuskagee Syphilis Experiment was a clinical study. Based on publications of indirect research using sera and cerebrospinal fluid, this article conceives a very history of the Tuskagee Syphilis Experiment. Syphilis could only cultivate in living beings. As in slavery, the generative ability of the body made the Tuskegee subjects real property and gave untreated syphilis and the sera of the Tuskegee subjects immense commercial value. Published protocols exploited the Tuskegee Syphilis Experiment to invent and commercialize biotechnology for the applied science of syphilis serology. PMID- 7869409 TI - Pseudopapillary fibroelastoma of the mitral valve. AB - Papillary fibroelastomas are well-recognized benign cardiac neoplasms. They are primarily asymptomatic, but occasionally are associated with neurologic and cardiac symptoms. Pseudopapillary fibroelastomas presenting with usual clinical and echocardiographic manifestations of papillary fibroelastoma but lacking characteristic histologic features have not been described previously. This article describes a 42-year-old, previously healthy female admitted with sudden hemiparesis and dysarthria. Symptoms completely resolved within 4 days. Extensive investigations revealed no etiology except for a pedunculated mitral valve mass with echocardiographic appearance suggestive of papillary fibroelastoma. Histologic staining, however, failed to reveal characteristic features of papillary fibroelastoma. PMID- 7869410 TI - Are hypertensives hypercoagulable? AB - Angiotensin II is a prothrombotic vasoconstrictor. This study proves that many hypertensives are hypercoagulable and at risk for myocardial infarction. The modified recalcification time (MRT) test, used to assess hypercoagulability, incorporates the role of tissue factor in coagulation by activating the monocyte with endotoxin to release latent tissue factor. Aliquots of citrated blood obtained from hypertensives and normotensive controls were placed in two groups of vials, one with saline (group S) and one with endotoxin (group E). All vials were incubated at 37 degrees C for 2 hours, citrate neutralized with calcium chloride, and the MRT (in minutes) for group S (MRT S) and for group E (MRT E) was determined. Mean MRT S values +/- standard deviation (SD) for hypertensives (n = 25) and for controls (n = 27) were 6.4 +/- 1.2 and 6.8 +/- 1.2, respectively. The MRT E values were 4.3 +/- 1.2 and 5.7 +/- 0.9 for the hypertensives and controls, respectively. The MRT E, not the MRT S, was significant. Hypertensives had MRT E values < 4.5 minutes, and by our established criteria, were hypercoagulable. We conclude that because hypercoagulability is a risk factor for thrombosis, hypertensives with short MRT E values may be at increased risk for myocardial or other thrombotic events. PMID- 7869411 TI - TennCare and national health-care reform. PMID- 7869412 TI - Endosteal implants and iliac crest grafts to restore severely resorbed totally edentulous maxillae--a retrospective study. AB - Autogenous grafts in conjunction with endosteal implants may be indicated in conditions of severe atrophy of the maxilla. From July, 1984, to December, 1990, 20 severely atrophic arches were restored with iliac crest onlay block grafts, subantral augmentation, and 148 endosteal root-form implants. Twenty-one implants were placed at the same time as the graft to stabilize a corticotrabecular bone block. Two implants were lost (90% implant survival). One hundred twenty-seven implants were placed after graft maturity, and one implant was removed (99% implant survival). Thirteen fixed restorations and 7 completely implant-supported overdentures were fabricated. Follow-up evaluation of prostheses and implants ranged from 26 to 97 months. All the implants used for initial prosthesis fabrication and all initial prostheses remain in function. The advantages of implant placement after graft maturity and subantral augmentation are addressed. One year after implant placement, the amount of additional bone lost around the implants placed in grafted bone is similar to the bone loss around maxillary implants inserted into non-grafted bone. PMID- 7869413 TI - Linear tomography in conjunction with pantomography in the assessment of dental implant recipient sites. AB - Tomography provides a three-dimensional unobstructed and anatomically accurate picture of the region being viewed. Tomography is a radiographic technique in which a "slice" or section of a given internal body structure is imaged in a pre determined plane. The advantage of utilizing a tomographic evaluation along with a pantomographic survey is that the clinician may examine the exact position or depth in all three planes of visualization. This radiographic modality can also reveal the quality and quantity of alveolar bone in a pre-determined implant site. This information would allow the clinician better to diagnose, plan treatment, and place dental implants more precisely. Therefore, the utilization of laminar or computerized tomography along with pantomography for more precise visualization and accurate measurement of available alveolar bone of the buccal lingual and labial-palatal perspective will be discussed and illustrated. PMID- 7869414 TI - The position of the mental foramen in Asian Indians. AB - The modal or most common position of the mental foramen in the human mandible with respect to teeth appears to be below the second premolar regardless of race or age. The position of this structure was investigated in a sample of Asian Indians of unknown age or sex. In this study, 75.36% of 138 mandibular sides exhibited the position of the mental foramen to be located directly below the second premolar. In addition, 6.62% of the mandibles possessed accessory mental foramina. The results of this study do not support those reported in some commonly used textbooks on anatomy, anesthesia, and anthropology concerning the position of the mental foramen in the human mandible. PMID- 7869415 TI - Restoration of the atrophic, edentulous mandible. AB - Twenty-five years' experience in treating the atrophic mandible has convinced us that the ramus frame is the finest service we can provide the patient who is afflicted with this condition. Modifications in the design and placement have solved problems encountered with past use of this treatment modality. When one considers the relative comfort and function resulting from a fully-implant supported prosthesis, the moderate cost of this one-piece custom-fabricated implant, and the fact that the implant and overdenture can be placed in one appointment, we believe that a resurgence will take place in the use of this treatment modality. The patient's ability to have immediate function, although limited to softer foods, is due to the large area of cortical bone supporting the implant. The most appreciative group of patients within our large implant practice consists of those patients who have had this procedure. PMID- 7869416 TI - The use of the subepithelial connective tissue graft to enhance both the aesthetics and periodontal contours surrounding dental implants. AB - The subepithelial connective tissue graft is a gingival grafting plastic surgery procedure that can be used to enhance the aesthetic and gingival contour of the periodontium around dental implants. This technique is described and illustrated to create a soft-tissue root prominence and mask the grey color penetrating the thin labial attached gingival tissues over dental implants. PMID- 7869417 TI - A low-profile Hader-bar system for implant-supported overdentures with minimum vertical clearance. AB - A method for treating a minimum vertical clearance maxillary overdenture patient is detailed. A low-profile, cemented, Hader bar with parallel guiding planes is used to stabilize a maxillary implant-supported overdenture. This system maximizes implant support while maintaining simple construction, ease of oral hygiene maintenance, good space for excellent esthetics, and allows enough acrylic bulk for long-term service. PMID- 7869418 TI - Expression of the putative pheromone and odorant transporter vomeromodulin mRNA and protein in nasal chemosensory mucosae. AB - In nasal chemosensory systems, glandular proteins associated with the vomeronasal and olfactory epithelia perform specific perireceptor functions associated with sensory transduction. Vomeromodulin, a recently identified glycoprotein synthesized by the lateral nasal glands, is proposed to be a pheromone transporter (Khew-Goodall et al., FASEB J 5:2976-2982, 1991). In our study, we have investigated its expression in vomeronasal, olfactory, and respiratory nasal mucosae of rats and humans using in situ hybridization and immunocytochemical techniques. In the rat, vomeromodulin mRNA and protein were localized abundantly in the glandular acini of the maxillary sinus component of the lateral nasal glands. In addition, the vomeronasal and posterior glands of the nasal septum also expressed vomeromodulin mRNA and protein. Vomeromodulin immunoreactivity was localized extracellularly in the mucus of the sensory and non-sensory epithelia of the vomeronasal organ, and in the mucociliary complex of the olfactory, respiratory, and associated nasal epithelia. In human nasal mucosae, vomeromodulin immunoreactivity was localized in the mucociliary complex of the vomeronasal and respiratory epithelia. Comparison of the localization of vomeromodulin with that of odorant-binding protein, which is also synthesized in the lateral nasal glands of rats, revealed that odorant-binding protein was expressed in a completely separate glandular region, namely the ventral component. In the septal glands, vomeromodulin was expressed in the posterior glands whereas odorant-binding protein was localized in the anterior glands. Odorant-binding protein immunoreactivity was not observed in the vomeronasal glands. In contrast, both proteins were localized in the mucus of vomeronasal, olfactory, and respiratory epithelia. Our results suggest that vomeromodulin, like odorant-binding protein, functions as a chemosensory stimulus transporter associated with perireceptor processes in vomeronasal and olfactory transduction. PMID- 7869419 TI - Proliferation and differentiation of fetal human oligodendrocytes in culture. AB - Phenotypic expression and proliferative capacity of the cells of oligodendrocyte lineage were investigated in primary cultures isolated from fetal human brains of 12-15 weeks' gestation using double immunolabeling with Ranscht-monoclonal antibody (R-mAb) or O4 and antibromodeoxyuridine (BrdU) antibody. Cultured cells of oligodendrocyte lineage consisted of a major population of R-mAb+O4- cells and minor populations of R-mAb-O4+ and R-mAb+O4+ cells. Most of the R-mAb+O4- cells exhibited a uni-, bi-, or tripolar immature morphology, while the majority of the R-mAb+O4+ cells exhibited a multipolar mature morphology. R-mAb-O4+ cells contained a mixture of immature and mature cell types. When incubated in serum free culture medium containing BrdU for 4 days, 42% of total oligodendrocytes expressed nuclear BrdU immunolabeling. R-mAb+ cells exhibited a higher degree of BrdU immunolabeling, indicating that they have greater capacities for proliferation than O4+ cells. The large majority of BrdU+ cells exhibited an immature morphology. Inclusion of insulin, insulin-like growth factor (IGF)-I, basic fibroblast growth factor (bFGF), or fetal bovine serum in culture medium did not stimulate proliferation of oligodendrocytes, while platelet-derived growth factor (PDGF) or PDGF plus bFGF increased the number of R-mAb+BrdU+ and O4+BrdU+ cells over control, even though the results were not statistically significant. In addition, insulin and IGF-I induced a 3-fold increase in the number of R-mAb+O4+ cells, indicating that they promoted differentiation of oligodendrocytes. The present study indicates that fetal human oligodendrocytes in culture exhibit a considerable degree of proliferative capacity without requirement of exogenous growth factors and that both insulin and IGF-I promote their differentiation. PMID- 7869420 TI - Developmental expression of protein kinase C isozymes in oligodendrocytes and their differential modulation by 4 beta-phorbol-12,13-dibutyrate. AB - Myelin gene expression in normal oligodendrocytes (OLG) depends on developmentally regulated protein kinase C (PKC) enzyme activity (Asotra and Macklin: J Neurosci Res 34:571-588, 1993). We studied the developmental expression of the Ca(++)-dependent PKC-alpha, -beta 1, -beta II and -gamma isozymes, and the Ca(++)-independent PKC-delta, -epsilon, -zeta and -eta isozymes in enriched rat brain OLG cultures. In A2B5+ O-2A progenitors, only PKC-delta, PKC-epsilon and PKC-zeta were detected immunocytochemically. In 04+ proligondendrocytes, PKC-beta I, -delta and -zeta were expressed moderately and low levels of PKC-alpha and -epsilon were detected. GD3+ OLG, GC+ OLG and MBP+ OLG showed increased levels of PKC-alpha, -beta I, -delta and -zeta isozymes. PKC beta II, -gamma and -eta were poorly expressed in OLG. On immunoblots, PKC-alpha was present early and increased continually up to 18 days but PKC-beta I increased until 12 days in cultured OLG. High levels of PKC-delta, PKC-epsilon and PKC-zeta, the most abundant PKC isozymes in OLG, were maintained up to 12 days and were then slightly reduced. Interestingly, relatively high levels of PKC alpha, PKC-beta I, PKC-beta II, PKC-gamma and PKC-epsilon isozymes were detected in purified myelin membrane although greater levels of PKC-delta were found in OLG than in purified myelin. Thus, most of the PKC isozymes found in cultured OLG were also present in myelin, although at different levels. Treatment with 50 nM 4 beta-phorbol-12,13-dibutyrate (PDB) caused a delayed downregulation of PKC-delta levels after 8 hr without modulating the expression of other PKC isozymes in 1 day OLG; in the 3-day-old and 6-day-old OLG, PDB downmodulated PKC-beta I, -delta and epsilon isozymes with only a minor effect on PKC-alpha and no reduction in PKC-zeta. Induction or downmodulation of individual PKC isozymes by phorbol esters appears to depend on the differentiation state of OLG. These data suggest that PKC-beta I, -delta and -epsilon isozymes have an important function in different cellular events of OLG differentiation. We conclude that the PKC dependent modulation of myelin gene expression in OLG results predominantly from the Ca(++)-dependent PKC-beta I isozyme activity and the CA(++)-independent PKC delta and PKC-epsilon activitives in a cell differentiation state-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7869421 TI - Prolonged alkylcatechol-induced expression of c-jun proto-oncogene followed by elevation of NGF mRNA in cultured astroglial cells. AB - We have already shown that alkylcatechol markedly enhances synthesis/secretion of nerve growth factor (NGF) in cultured mouse fibroblasts and astroglial cells through immediate accumulation of NGF mRNA and that the stimulatory effect of alkylcatechol on NGF synthesis/secretion is synergistically enhanced by the coadministration of phorbol 12-myristate 13-acetate (PMA). The stimulatory effect on NGF mRNA expression of astroglial cells in culture by 4-methylcatechol (MC), an alkylcatechol, and/or PMA was blocked by treatment of the cells with cycloheximide, suggesting de novo synthesis of some cellular protein(s) is essential for the observed increase in the NGF mRNA level. The exposure to MC and/or PMA caused a rapid increase in c-fos mRNA content, which was immediately followed by an increase in c-jun mRNA, prior to NGF mRNA elevation. The expression of c-fos mRNA was transiently enhanced in all cases of the treatment with MC and/or PMA. The c-jun mRNA expression was also observed transiently when the cells were treated with PMA alone, while the expression of c-jun mRNA was pronounced and long-lasting after the treatment with MC, which was much further enhanced by the coadministration of PMA. The result that the profile of the change in c-jun mRNA expression resembled that in NGF mRNA expression suggests that the increase in c-jun mRNA is responsible for the subsequent increase in NGF mRNA after MC treatment. The contransfection of mouse astroglial cells with expression plasmids of c-fos and/or c-jun and NGF promoter gene showed that simultaneous expression of both c-fos and c-jun genes was necessary to enhance NGF promoter activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869422 TI - Deafferentation removes calretinin immunopositive terminals, but does not induce degeneration of calbindin D-28k and parvalbumin expressing neurons in the hippocampus of adult rats. AB - Unilateral combined transections of the fimbriafornix and angular bundle in adult Fischer 344 rats were used to study the effects of deafferentation on hippocampal expression of calretinin, calbindin D-28k, and parvalbumin. Reflecting the widespread degeneration of synaptic contacts, immunostaining for glial fibrillary acidic protein 6 days after the lesions was increased in lacunosum-molecular and oriens layers of CA1, 2, and 3 in ipsi- and contralateral hippocampus and in the ipsilateral dentate gyrus outer molecular layer. At 21 days the immunoreactivity had decreased to control levels except for a still slightly increased signal in the oriens layer of CA1-3. At 6 and 21 days after the combined lesions the numbers of hippocampal neurons containing calretinin, parvalbumin, and calbindin D-28k was unaltered. The combined lesions abolished calretinin containing terminals in the dentate gyrus inner molecular layer on the deafferentated side. This could be reproduced by single unilateral fimbria-fornix transections, suggesting that the axons of these calretinin positive terminals project to the hippocampus through the fimbria-fornix. The most likely origin of the calretinin positive terminals are neurons in the supramammillary hypothalamic nucleus. Our findings demonstrate that the extensive lesion-induced synaptic rearrangements in the adult hippocampus do not induce degeneration of hippocampal neurons expressing calretinin, calbindin D-28k, and parvalbumin, but do remove calretinin containing terminals which reach their targets in the hippocampus through the fimbria-fornix. PMID- 7869423 TI - Responsiveness of cultured septal and hippocampal neurons to ethanol and neurotrophic substances. AB - Dissociated septal and hippocampal neurons from E18 fetal rats were cultured with varying concentrations of ethanol (0.6-2.4 g/dl) and in cultures containing ethanol plus nerve growth factor (NGF) or basic fibroblast growth factor (bFGF). These substances have been shown to provide neurotrophic support for these populations and to afford neuroprotection against certain toxic substances or conditions applied to some neuronal populations. Both the septal and hippocampal neurons responded to ethanol in a dose-dependent manner. Survival of septal neurons was generally unaffected by initial ethanol concentrations of 0.6 and 1.2 g/dl but was considerably impaired by higher concentrations (1.8 and 2.4 g/dl), while neurite outgrowth was compromised by all ethanol concentrations except the lowest one applied. The hippocampal neurons survived ethanol concentrations up to 2.4 g/dl, although process extension was decreased in concentrations of 1.2 g/dl and higher. NGF or bFGF in the culture medium (in cultures without ethanol) did not affect neuronal survival or process outgrowth in either population, probably owing to the relatively high plating densities of the cultures. NGF did tend to have a moderate ameliorative effect on the ethanol neurotoxicity in the septal cultures, however, and was slightly effective in this regard in hippocampal cultures at intermediate ethanol concentrations (1.8 g/dl). High concentrations of ethanol (2.4 g/dl) reduced the proportion of cholinergic cells in the septal preparations by approximately 50%. This neuronal loss could be reversed by inclusion of high concentrations of NGF in the culture medium (100 ng/ml) but not by a lower concentration (20 ng/ml). bFGF provided some protection against ethanol cytotoxicity with respect to both populations. The implications of these results for studies of fetal alcohol effects are discussed, as well as their relation to prior reports of trophic factor neuroprotection. PMID- 7869424 TI - Normal distribution of alpha 2-adrenoceptors in the rat spinal cord and its modification after noradrenergic denervation: a quantitative autoradiographic study. AB - The distribution of alpha 2 (alpha 2)-adrenoceptors along cervical, thoracic, lumbar, and sacral segments of the spinal cord of normal rats has been studied by quantitative autoradiography using the specific alpha 2-antagonist [3H]rauwolscine as a ligand. In addition, the influence of noradrenergic (NA) denervation [obtained either by complete transection of the spinal cord at vertebrae level T8-T9 or by selective lesion of NA spinal cord system carried out by intracisternal injection of 6-hydroxydopamine (6-OHDA)] on eventual variations of alpha 2-adrenoceptor density at spinal cord target cells was studied in parallel. In control rats, the quantitative analysis of alpha 2-adrenoceptor densities revealed the presence of these receptors throughout the whole gray matter with a preferential location in the superficial dorsal horn. This pattern was the same at all rostro-caudal levels of the cord and appeared very well correlated with the distribution of NA terminals revealed by immunohistochemistry, particularly in the superficial layers of the dorsal horn. After total transection of the spinal cord (caudally to the section) and 6-OHDA induced lesion, an increase of alpha 2-adrenoceptor density was mainly observed within the distal dorsal horn thus evidencing supersensitivity in this area, while modifications were not detectable in other regions of the spinal gray matter, except at the lumbar level where other dorsal, central, and intermediate zones were significantly enriched. PMID- 7869425 TI - Effects of the N-acetylgalactosaminyltransferase inhibitor on cultured cerebral cells. AB - The inhibitor preparation of the UDP-N-acetylgalactosamine: GM3, N acetylgalactosaminyltransferase (EC 2.4.1.92) (GalNAc-T) produces effects on the neurons and the glial (astrocytes) cells of the cerebrum in culture. The effect in culture is evidenced by aneuritogenesis, deficiency in the GalNAc-T activity, and decrease in the content of gangliosides, proteins, and lipids. In isolated glial cells the effect is evidenced by cytoplasm vesiculation and premature cessation of proliferation compared with control culture. The pattern of gangliosides in the inhibited culture shows a decrease in the amount of GD1a with respect to GD3; this is compatible with the notion that the effect is due to an inhibitor of the GM2 synthase. The inhibitor effects are reverted when it is eliminated after 24 or 48 hr in the culture medium. PMID- 7869426 TI - Regional CNS uptake of blood-borne nerve growth factor. AB - Nerve growth factor (NGF), in addition to being a neurotrophic substance, has effects on the endocrine and immune systems. For example, intravenous injection of NGF results in a cascade of events leading to an increase in glucocorticoid secretion. While this response appears to be mediated centrally, there has been no evidence that circulating NGF has access to the CNS. Using intravenous injections of 125I-NGF, we find specific uptake at 1 hr but none at 6 hr, into homogenates of the basal forebrain, cerebellum, frontal cortex, hippocampus, and olfactory bulb. By autoradiography, uptake is localized to circumventricular organs, deep layers of the cerebellum, and all layers of the hippocampal region CA1, but not the dentate gyrus. Thus, uptake of blood-borne NGF could affect the hypothalamic-pituitary-adrenal axis via binding to NGF receptors present in the hippocampus. However, the sources of endogenous NGF, the mechanism of access through the blood-brain barrier, the eventual fate of NGF entering from the blood, and the physiological significance of this uptake remain to be elucidated. PMID- 7869427 TI - Toxic axonal degeneration occurs independent of neurofilament accumulation. AB - Alteration of neurofilament (NF) proteins is considered a critical component and a causative factor for a number of neuropathologies, especially certain neurotoxicities. Correlative observations have supported this hypothesis; the current study tests this relationship by exposure of neurotoxicants to crayfish, a species lacking NFs. Morphological and immunological tests verified the absence of NFs in crayfish peripheral nerve axons. Tail injections of acrylamide (ACR), 2,5-hexanedione (2,5-HD), or 3,4-dimethyl-2,5-HD (3,4-DMHD) produced ataxia and paralysis. Morphological expression of axonal degeneration in a spatial and temporal pattern of progression comparable to mammalian species possessing NFs was observed. With gamma-diketones, time to onset was slower than observed in mammals but relative potency between neurotoxic analogues was maintained. Non neurotoxic analogues failed to produce any functional signs of neurotoxicity. These data are consistent with the conclusion that NF accumulations are not cause effect related to axonal degeneration in these models of neurotoxicity and raise questions as to the relationship between accumulation of NF proteins and axonal degeneration in other neuropathological conditions. PMID- 7869428 TI - The role of firearms and violence. PMID- 7869429 TI - The role of firearms and violence. PMID- 7869430 TI - Violence in America: a public health crisis--The role of firearms. The Violence Prevention Task Force of the Eastern Association for the Surgery of Trauma. PMID- 7869431 TI - Coronal fracture of the body of the hamate. AB - Fractures of the body of the hamate are unusual. Eleven patients with coronal fractures of the hamate bone, all involving dislocation of the hamate-metacarpal joint, are reported. Routine roentgenograms were not helpful in delineating the presence of the injury in five patients; therefore, fracture diagnosis was not initially made in those patients. The average delay in diagnosis of this group was 10 days. A 30-degree pronated view, tomograms, and computed tomography scans may be necessary in the diagnosis of this injury. This fracture was found to be highly unstable. Ten patients underwent surgery for stabilization of their fractures and restoration of the congruity of the hamate-metacarpal joint. Four patients were treated with open reduction and internal fixation of the fracture. Six patients were treated with closed reduction and percutaneous pinning. All patients treated surgically had maintenance of reduction of their joints. One patient was treated with closed reduction and casting; reduction in this case was lost, and the patient developed residual subluxation of the hamate-metacarpal joint. PMID- 7869432 TI - Increased early postburn fluid requirements and oxygen demands are predictive of the degree of airways injury by smoke inhalation. AB - The combination of burn and smoke inhalation was studied to determine if early hemodynamic and metabolic abnormalities would correspond with the degree of subsequent smoke-induced airways injury. Adult sheep (n = 45) given an 18% total body surface third-degree burn alone or with smoke exposures of 12 breaths of 5, 10, or 20 mL/kg tidal volume were continuously monitored with airways assessed at 4 or 24 hours. With increased smoke exposure (20 mL/kg tidal volume), oxygen consumption (VO2) in the first several hours and net positive fluid balance, especially in the first 6 hours, increased by 100% and 300%, respectively, over that seen with burn alone. The degree of increase in fluid requirement, net fluid retention, and VO2 with smoke, compared with burn alone, correlated best with the degree of airways damage quantitated at 24 hours, r = 0.83, 0.85, and 0.89, respectively. Airways damage at 4 hours did not predict the damage seen at 24 hours. Systemic changes were not caused by gas-phase toxins, such as carbon monoxide, because smoke filtered of particles had the same blood carbon monoxide control as whole smoke, but the systemic response was equal to burn alone, and there was no airways injury. The cause of the systemic changes is likely the result of the intense airways inflammation. PMID- 7869433 TI - Epidemiology of trauma deaths: a reassessment. AB - OBJECTIVE: Recognizing the impact of the 1977 San Francisco study of trauma deaths in trauma care, our purpose was to reassess those findings in a contemporary trauma system. DESIGN: Cross-sectional. MATERIAL AND METHODS: All trauma deaths occurring in Denver City and County during 1992 were reviewed; data were obtained by cross-referencing four databases: paramedic trip reports, trauma registries, coroner autopsy reports and police reports. MEASUREMENTS AND MAIN RESULTS: There were 289 postinjury fatalities; mean age was 36.8 +/- 1.2 years and mean Injury Severity Score (ISS) was 35.7 +/- 1.2. Predominant injury mechanisms were gunshot wounds in 121 (42%), motorvehicle accidents in 75 (38%) and falls in 23 (8%) cases. Seven (2%) individuals sustained lethal burns. Ninety eight (34%) deaths occurred in the pre-hospital setting. The remaining 191 (66%) patients were transported to the hospital. Of these, 154 (81%) died in the first 48 hours (acute), 11 (6%) within three to seven days (early) and 26 (14%) after seven days (late). Central nervous system injuries were the most frequent cause of death (42%), followed by exsanguination (39%) and organ failure (7%). While acute and early deaths were mostly due to the first two causes, organ failure was the most common cause of late death (61%). CONCLUSIONS: In comparison with the previous report, we observed similar injury mechanisms, demographics and causes of death. However, in our experience, there was an improved access to the medical system, greater proportion of late deaths due to brain injury and lack of the classic trimodal distribution. PMID- 7869434 TI - Negative laparotomy in abdominal gunshot wounds: potential impact of laparoscopy. AB - OBJECTIVE: To evaluate the morbidity and hospital stay resultant from negative exploratory laparotomy (NL) for abdominal gunshot wounds (ABGSWs) and the potential impact the use of diagnostic laparoscopy (DL) could have on these variables. DESIGN: A retrospective study was conducted. MATERIALS AND METHODS: The charts of all patients with ABGSWs over a 4-year period were reviewed. Data was collected on injuries, rate of NL, morbidity and hospital stay. This was compared to a subsequent group of patients with ABGSWs managed with a DL protocol. MEASUREMENTS AND MAIN RESULTS: Over a 4-year period, 817 patients had exploratory laparotomy (EL) for ABGSWs. The NL rate was 12.4% (101 of 817); 69 of these patients had no associated injury or other procedures. They had a 22% morbidity and an average hospital stay of 5.1 days. Subsequently, 85 patients with ABGSWs underwent DL. This group was similar to the EL group and would have undergone EL prior to the introduction of DL at our institution. In this group, 34 patients had no associated injury or other procedures. They had a 3% morbidity, and their average hospital stay was 1.4 days. The morbidity and hospital stay were statistically significantly reduced (p < 0.01) in patients with negative DL versus NL. CONCLUSIONS: These data demonstrate that NL is associated with a high morbidity and long hospital stay. The use of DL can reduce the rate of NL, and result in lower morbidity and shorter hospital stay in patients with ABGSWs. PMID- 7869435 TI - Chronic ethanol intake and burn injury: evidence for synergistic alteration in gut and immune integrity. AB - OBJECTIVE: Chronic ethanol (EtOH) intake and injury are both associated with increased susceptibility to infection in the host. This study examined the immune and gastrointestinal alterations induced by chronic EtOH intake and injury, and compared the effects of enteral and intravenous administration of EtOH. DESIGN: Rats received 20% EtOH daily for 14 days by gavage [oral (PO)] or superior vena cava [intravenous (i.v.)] infusion. Mean blood EtOH concentrations at 90 minutes after administration were 95.3 mg/dL (PO) and 94.4 mg/dL (i.v.). An additional group of animals underwent a 30% total body surface area full-thickness burn injury 4 hours after the final dose of EtOH or normal saline on experimental day 14. All animals were killed 4 days after burn injury. MATERIALS AND METHODS: Nonadherent splenic lymphocytes were tested for mitogenic responses to the T-cell mitogens concanavalin A (ConA) and phytohemagglutinin (PHA), and the B-cell mitogens lipopolysaccharide (LPS) and pokeweed. Quantitative bacterial cultures of mesenteric lymph nodes and liver were also performed. Alterations of intestinal mucosa were determined by measurement of ileal mucosal weight, DNA, protein, and diamine oxidase content. Circulating plasma endotoxin concentrations were also measured. MEASUREMENTS AND MAIN RESULTS: Chronic PO-EtOH intake induced a significant impairment in mitogenic response to T-cell mitogens, with a fourfold reduction in ConA and a twofold reduction in PHA response (p < 0.05 by analysis of variance) and increased bacterial translocation (70% vs. 10%). Chronic EtOH administered by the i.v. route did not reduce mitogenic response to any of the mitogens studied. Histologic examination of ileal segments demonstrated that chronic PO-EtOH administration was associated with significant mucosal disruption and exfoliation. Chronic administration of PO-EtOH prior to burn injury induced a significant impairment in spleen mitogenic response to ConA, PHA, and LPS when compared with all other burn injury groups. Chronic administration of EtOH by the i.v. route prior to burn injury did not alter splenic mitogenesis. In addition, chronic PO-EtOH prior to burn injury increased bacterial translocation rates (80% vs. 33%) and prevented the normal intestinal reparative response to burn injury (demonstrated by a significant reduction in ileal mucosal weight, DNA, and diamine oxidase content). CONCLUSIONS: Enteral but not i.v. administration of EtOH induced significant immunologic dysfunction (demonstrated by altered spleen mitogenic response) and gastrointestinal dysfunction (demonstrated by depressed ileal mucosal weight, DNA, and diamine oxidase content, and increased bacterial translocation rates). In addition, the administration of chronic enteral EtOH prior to injury resulted in significant immune suppression and impaired the host's ability for normal intestinal repair. These results suggest that this EtOH-induced reduction in immunocompetence may be gut-mediated and that the administration of alcohol prior to injury may result in a synergistic alteration of gut and immune integrity. PMID- 7869436 TI - Fatal hemorrhage caused by vascular injury associated with an acetabular fracture. AB - We present a case of a widely displaced double-column acetabular fracture associated with lacerations of the ipsilateral common iliac artery and vein, resulting in a fatal hemorrhage. This case illustrates the importance of considering the possibility of a concomitant vascular injury in the assessment of a patient with an acetabular fracture and otherwise unexplained hemorrhage. PMID- 7869437 TI - Double-rib composite free transfer to reconstruct a single-spared lower extremity defect. AB - The case of a 43-year-old man is reported in which a 15-cm defect of the tibia sustained 8 months previously was treated by the double-rib composite microvascular free transfer. The fracture site united, and the grafted ribs showed some hypertrophy at 1 year. He returned to his job. At 5 years follow-up, the x-ray film showed good hypertrophy of the grafted ribs. PMID- 7869438 TI - Femoral torsion after interlocked nailing of unstable femoral fractures. AB - OBJECTIVE: The determination of rotation of the femur during intramedullary nailing procedures can be difficult, particularly when the fracture pattern does not lend itself to interdigitation. We studied 22 patients who had isolated femur fractures treated by closed intramedullary nailing to determine the degree of malrotation introduced at the time of surgery. DESIGN AND METHODS: Anteversion of the affected and normal femora was determined by a standard computed tomography (CT) torsion study. The range of motion of the hip was measured in the prone position. Foot progression angles (FPAs) were measured in 14 patients who were fully ambulatory for at least 6 months. MAIN RESULTS: The average malrotation of the fractured femur was 16 degrees (4 to 61 degrees). The median malrotation was 14 degrees. The differences in CT-measured anteversion (delta A), FPA (delta FPA), internal rotation (delta IR), and external rotation (delta ER) between the affected and normal sides were determined. Linear regression was used to analyze delta A with delta FPA, delta IR, and delta ER. Changes in internal and external rotation as determined by physical exam had a stronger correlation with delta A than did delta FPA. This indicates that malrotation of the femur is accommodated for during gait. CONCLUSIONS: Based on this data, we found that anteversion of the normal femur can be determined in the operating room using the image intensifier and can be duplicated on the fractured side using the described technique in cases where comminution prevents fragmentational alignment. This method has been used for 12 patients in a prospective trial, and malrotation has been kept to under 10 degrees in all cases. PMID- 7869439 TI - Medical cost containment: analysis of dual orthopedic/radiology interpretation of X-rays in the trauma patient. AB - OBJECTIVE: The purpose of this study was to investigate the timing, accuracy, clinical impact, and cost of dual orthopedic and radiology interpretation of orthopedic trauma roentgenograms. DESIGN: The investigation was performed in a combined retrospective-prospective fashion. MATERIALS AND METHODS: Records of 25 retrospective and 25 prospective trauma patients with femoral fractures were reviewed and the radiology and orthopedic roentgenographic interpretations were compared in terms of four criteria: timing, accuracy, clinical impact, and cost. MEASUREMENTS AND MAIN RESULTS: The orthopedic surgeons documented reading 85% of 272 acute roentgenograms in the retrospective patients and 89% of 181 roentgenograms in the prospective patients. The orthopedist readings were immediate, 100% accurate, had significant impact on the patients' care, and incurred no additional cost. The radiologists read 59 and 75% of the retrospective and prospective roentgenograms, respectively. The accuracy rate was 94 and 96%, the time to reading averaged 7 and 4.6 days, and the estimated cost averaged $393 and $200 per patient, respectively. The radiologist readings had no impact on patient care. CONCLUSION: This study suggests that routine radiology consultation of musculoskeletal films read by the orthopedic surgeon is not required for the care of the acute trauma patient. PMID- 7869440 TI - Detection of acute bacterial infection within soft tissue injuries using a 99mTc labeled chemotactic peptide. AB - OBJECTIVE: Infection imaging with a 99mTc-labeled chemotactic peptide was evaluated in a rabbit model of Escherichia coli infections in burned tissue. MATERIALS AND METHODS: The peptide was radiolabeled with 99mTc via the hydrazino nicotinamide derivative. Three groups of six animals were studied: (group A) unilateral infected burns; (group B) bilateral burns with unilateral infection; and (group C) uninfected burns. Twenty-four hours after injury, groups A and B were infected, and 8 hours later, all animals were injected with approximately 0.50 mCi of 99mTc-peptide. MEASUREMENTS AND MAIN RESULTS: In groups A and B, excellent images of the infections were obtained at 3 to 4 and 16 to 18 hours after injection of the peptide. At 3 to 4 hours after injection, the target-to background ratios (T/B) were 3.12 +/- 0.28 for group A and 4.33 +/- 0.61 for group B (p = n.s.). At 16 to 18 hours, the T/B ratios increased significantly (p < 0.01): group A = 8.10 +/- 1.03 and B = 7.70 +/- 1.25. The T/B ratio for group C was only slightly greater than unity. CONCLUSIONS: These results indicate that 99mTc-labeled chemotactic peptides are effective radiopharmaceuticals for the rapid detection of focal sites of infection within thermally injured tissues. PMID- 7869441 TI - Geographic variation in preventable deaths from motor vehicle crashes. AB - OBJECTIVE: In Michigan, drivers in rural motor vehicle crashes (MVCs) are twice as likely to die as nonrural drivers: this could be due to variation in the quality of acute trauma care. This study tests the hypothesis that the preventable death rate (PDR) is higher and that anatomic injury severity is lower for rural compared to nonrural MVC fatalities. DESIGN: Retrospective cohort study. METHODS: Autopsy results from MVC victims of three rural counties and one nonrural county were reviewed. The time period was 1986-1991. Using the Abbreviated Injury Scale, 1985 version (AIS-85), Injury Severity Scores (ISSs) and Anatomical Profile G scores were calculated. Preventability was determined based on ISSs (< 59) and AIS scores in the head region (< 5). Student's t test and the chi-squared test were used for analysis; a p value of < 0.05 was considered statistically significant. RESULTS: 143 rural and 306 nonrural fatalities were analyzed. The rural PDR was 37.1% and nonrural 48.0% (p < 0.05). ISSs and also G scores were significantly different between rural (54.8; -2.1) and nonrural (50.2; -1.2) areas. CONCLUSION: This study suggests that regional variation in the quality of acute trauma care is not a significant factor in regional variation in MVC mortality. PMID- 7869443 TI - Anabolic impact of cimaterol in conjunction with enteral nutrition following burn trauma. AB - Burn injury is characterized by increased energy expenditure, weight loss, and muscle protein wasting. Studies have shown that beta 2-adrenergic agonists have anabolic properties in the presence of increased metabolism. This study investigated the effects of the beta 2-agonist cimaterol in burned animals receiving enteral nutrition. Guinea pigs with gastrostomies were given a 30% total body surface area burn and fed for 14 days. Animals received saline or cimaterol (0.15 mg/kg, SC) twice daily. Energy expenditure was determined before burn and on postburn days 3, 6, 9, and 12. On day 14, the soleus, gastrocnemius muscles, and heart were excised and weighed as a measure of muscle catabolism and anabolism. Carcass weight was determined to measure muscle catabolism. Cimaterol increased (p < 0.05) total protein content, gastrocnemius muscle, and carcass weights. The soleus muscle and heart weights, and resting metabolic rates showed no significant differences. Results suggest enteral nutrition with cimaterol decreases burn-induced muscle catabolism. PMID- 7869442 TI - A double-blinded prospective evaluation of recombinant human erythropoietin in acutely burned patients. AB - OBJECTIVE: To evaluate the effects of recombinant human erythropoietin (r-HuEPO) in attempting to prevent anemia in acutely burned patients. DESIGN: Prospective double-blind randomized study of 40 patients. METHODS: Patients with burns from 25% to 65% total body surface were enrolled. r-HuEPO or a placebo was begun within 72 hours of admission. Cell blood count, reticulocyte counts, transfusion requirements, and blood loss were measured. Comparison was carried out by the unpaired t test. MAIN RESULTS: There was no statistically significant difference in hemoglobin, hematocrit, reticulocyte count, ferritin, serum iron, total iron blinding capacity, or transfusion requirements. In patients with burns from 25% to 35%, the reticulocyte counts were statistically significantly higher. CONCLUSION: In our work the administration of r-HuEPO in acutely burned patients did not prevent the development of postburn anemia or decrease transfusion requirements. Increased erythropoiesis in smaller burns (25% to 35%) was observed and may indicate a reason for further study. PMID- 7869444 TI - Fatal injuries in motorcycle riders according to helmet use. AB - OBJECTIVE: Helmets have been shown to be effective in preventing head injuries in motorcyclists, but some studies have suggested that helmets may cause injury to parts of the head or neck because they add mass to the head. DESIGN: This study examined patterns of fatal injuries in helmeted and unhelmeted motorcyclists. MATERIALS AND METHODS: Coroner reports, hospital records, and police reports for motorcyclists fatally injured in crashes from July 1, 1988 through October 31, 1989 were examined. All injury diagnoses were abstracted and coded to the 1990 version of The Abbreviated Injury Scale and the International Classification of Diseases, 9th revision. MAIN RESULTS: Cerebral injury, intracranial hemorrhage, face, skull vault, and cervical spine injuries were more likely to be found in fatally injured unhelmeted motorcyclists than in helmeted motorcyclists. CONCLUSIONS: These results expand earlier reports showing that helmets provide protection for all types and locations of head injuries, and show that they are not associated with increased neck injury occurrence. PMID- 7869445 TI - Nonoperative treatment of a major hepatic injury in a hemophiliac. AB - Selective nonoperative management of hepatic injuries from blunt trauma has become an accepted practice over the past 10 years. A case of nonoperative management of a major hepatic injury in a person with Hemophilia A is reported. Treatment with aggressive blood component therapy resulted in a successful outcome. PMID- 7869446 TI - Percutaneous cholecystostomy in the critically ill burn patient. AB - OBJECTIVE: We desired to demonstrate the utility of percutaneous cholecystostomy in the evaluation and management of critically ill burn patients with fever and rising cholestatic chemistries. DESIGN: Retrospective review. MATERIALS AND METHODS: Over a 2 1/2-year period there were 411 admissions to a regional adult burn until of whom six patients (1.5%) were strongly suspected of having developed acute cholecystitis. Five were managed with percutaneous cholecystostomy. MEASUREMENTS AND MAIN RESULTS: All patients had sonographic signs consistent with acute cholecystitis. One was managed with immediate laparotomy and the remaining five patients underwent ultrasound-guided percutaneous transhepatic cholecystostomy at the bedside (n = 4) or in the ultrasonography suite (n = 1) without complication. One patient died of multiple organ failure 3 days after catheter placement despite good catheter position and function. Two of the surviving patients responded promptly to drainage of the gallbladder with resolution of fever and normalization of liver function tests. Two patients did not respond despite catheters that were properly placed and functioning, reliably eliminating the diagnosis of acute cholecystitis. One patient underwent interval cholecystectomy after wound closure and the remaining patients were discharged after catheters were removed. CONCLUSIONS: Bedside percutaneous cholecystostomy is a minimally invasive procedure that can facilitate the evaluation and management of the critically ill burn patient with fever and rising cholestatic chemistries in whom a diagnosis of acute cholecystitis is suspected. PMID- 7869447 TI - Torture rhabdomyorhexis--a pseudo-crush syndrome. AB - Two patients who were systematically tortured and deprived of any oral intake presented with acute renal failure several days later. Unlike the classical crush syndrome, we describe a clinical entity wherein repeated direct muscle injury from blunt trauma, in addition to forced dehydration, led to myoglobinuria and renal failure. The literature is reviewed, and biochemical indices predicting severity of injury, pathophysiology, and management protocol are described. This pseudo-crush syndrome caused by rhabdomyorhexis in addition to rhabdomyolysis is an unusual entity, in part related to extreme sociopolitical factors. PMID- 7869448 TI - Traumatic separation of the symphysis pubis during pregnancy: a case report. AB - OBJECTIVE: To present an unusual case of traumatic extensive separation of the symphysis pubis during pregnancy and rationale for mode of treatment. DESIGN: Diagnosis for etiology of public and lower back pain following trauma in a 37 year-old woman in an advanced stage of pregnancy. METHODS: Physical examination and plain anterioposterior X-rays. CONCLUSION: Extensive traumatic separation of the symphysis pubis might result from a very forceful descent of the fetal head against the pelvic ring upon the mother's accidental falling. Propitious timing of a caesarian section permits the option of open reduction and internal fixation. PMID- 7869449 TI - Neer's classification system: a critical appraisal. AB - The purpose of this study was to examine the interobserver agreement using Neer's classification system for fractures of the proximal humerus. A preliminary series of 28 fractures of the proximal humerus admitted to the hospital over a 5-year retrospective period was independently assessed by two radiologists and two orthopedic surgeons. The degree of agreement between paired observations was determined using a kappa statistic. The observations were assessed according to the number of fracture segments, as well as site of fracture segment. Most of the patients assessed were multisegment tuberosity fractures (n = 18). Results showed that the overall agreement between pairs of observers was 65% (average kappa = 0.45). It was also shown that, within the tuberosity group, the percentage agreement was 50%, with an average kappa = 0.35, indicating only fair interobserver agreement. Clinical implications of these findings are such that, as major surgical decisions are made dependent on Neer's classification, closer evaluation techniques--such as the computerized tomography scan and magnetic resonance imaging--should be used to classify the fracture segments accurately. This is particularly true with the fractured tuberosity subgroup. PMID- 7869451 TI - Occult pseudoaneurysm of the abdominal aorta following gunshot wound: the importance of plain film findings. AB - A traumatic pseudoaneurysm of the abdominal aorta eluded detection at initial laparotomy, but was later detected serendipitously. Early abdominal x-ray film and appreciation of paraspinal bullet fragments could have led to its earlier detection. A portable abdominal x-ray film should be a routine part of the preoperative resuscitation of abdominal gunshot wounds. PMID- 7869450 TI - Metaphyseal nonunion: a diagnostic dilemma. AB - Twenty-eight patients with metaphyseal nonunion were evaluated retrospectively. Initially, all patients were thought to have healing of their fractures. Mild pain and/or instability with weightbearing or discomfort localized around the hardware were common symptoms of this nonunion; however, substantial pain was not a predominant feature. In the majority of cases, routine roentgenograms were not helpful in establishing the diagnosis. Overlapping hardware made visualization difficult; furthermore, the presence of a callus gave a false impression of fracture healing. Tomograms were done in 13 patients, but were not helpful in four patients. Stress views and examination under fluoroscopy were reliable means of making this diagnosis, particularly around the knee region. It was done, however, only in a few patients. Subtle changes in the position of hardware or the position of the fragments are also an indication of failure of union. The average time from the initial injury to the diagnosis of nonunion was 36 weeks. Five patients whose pain was attributed to the hardware were found to have a nonunion intraoperatively at time of attempted hardware removal. In one patient, the nonunion was diagnosed during a quadricepsplasty. In two patients, the diagnosis was missed a second time following revision of fixation and bone grafting. Diagnosis of metaphyseal nonunion requires a high index of suspicion, because it occurs among all age groups. It is not as rare as previously described and poses many difficulties. The authors recommend the use of additional studies, including tomograms or stress views, oblique to establish difficult diagrams. PMID- 7869452 TI - Extraperitoneal rectal gunshot injuries. AB - Extraperitoneal rectal gunshot injuries are rare, but may be encountered in civilian practice. We report on a series of 26 such cases. The aim of the study is to attempt to evolve a treatment policy of this injury. The principles of management include the repair of rectal wound in selected cases and the formation of a diverting colostomy. Distal rectal washout and presacral drainage, although advocated by some authors, do not seem to be indispensable adjuncts to the management of these injuries. PMID- 7869453 TI - Mandatory toxicology testing and chemical dependence consultation follow-up in a level-one trauma center. AB - OBJECTIVE: There is a growing body of evidence indicating an association between intoxication and major trauma. This study assessed the prevalence of alcohol or drug intoxication in major trauma admissions to an urban trauma center. DESIGN: Sequential case series. METHODS: Toxicology testing and structural clinical interview assessment. MAIN RESULTS: Seventy-eight percent of patients tested had positive toxicology results. Chemical dependence assessments performed on patients who tested positive revealed that 94% met the criteria for a substance dependence or abuse disorder. CONCLUSIONS: The implications of this data for admission toxicology testing policies and chemical dependence consultation support services to trauma units are discussed. PMID- 7869454 TI - A prospective investigation of the impact of alcohol consumption on helmet use, injury severity, medical resource utilization, and health care costs in bicycle related trauma. AB - STUDY OBJECTIVE: To examine if a relationship exists between bicycle-related injuries, consumption of alcohol, helmet use, and medical resource utilization. DESIGN: A prospective cohort study with data from emergency department, operating room, and inpatient records. SETTING: University-based trauma center in a medium sized metropolitan area. TYPE OF PARTICIPANTS: Adult victims (age > or = 18 years) of bicycle-related injury presenting to the emergency department. A total of 350 patients made up the study population. RESULTS: Group 1 consisted of 29 patients (8.3%) with detectable blood alcohol levels at the time of the incident. Group 2 (321 patients) had a measured blood alcohol level of 0 or no clinical indication of alcohol consumption. Group 1 mean Injury Severity Score was 10.3, with six (20.7%) sustaining at least one severe anatomic injury. Group 2 had an Injury Severity Score of 3.3 (p < 0.0001), with only 4.4% (p = 0.0013) sustaining severe anatomic injury. Mean length of hospitalization for group 1 was 3.5 days, including a mean of 1.4 intensive care unit days. Mean hospitalization (0.5 days, p < 0.0001) and intensive care unit (0.1 days, p < 0.0001) were significantly lower in group 2. Mean combined hospital and physician charges were more than six times greater for group 1 ($7,206) than group 2 patients ($1170, p < 0.0001). CONCLUSION: In patients presenting with bicycle-related injuries, prior consumption of alcohol is highly associated with greater injury severity, longer hospitalization, and higher health care costs. This information is useful in the development of injury prevention strategies to decrease incidence and severity of adult bicycle injuries. PMID- 7869455 TI - Hospital costs of firearm injuries. AB - The purpose of this study was to provide economic, epidemiologic, and clinical data on initial hospitalizations of patients with firearm injuries. DESIGN: Concurrent prospective study; data obtained by medical records review. SETTING: A county university teaching hospital designated a level I trauma center. SUBJECTS: 34,893 persons first hospitalized for firearm injuries at the King/Drew Medical Center in Los Angeles from January 1978 through December 1992. RESULTS: The aggregate hospital cost for 34,893 firearm injuries, exclusive of professional fees, was $264,506,455.00, of which 96% was borne directly or indirectly by public funds. The charge for initial hospitalizations was $240,700,855.00. Mean and median initial charges per case were $6898.00 and $1,022.00, respectively (range, $944.00 to $296,232.00). The 5% of patients with charges greater than $100,000 accounted for 42% of all charges; 45% of all patient days were attributable to the 4% patients, with hospitalizations lasting more than 30 days. Three thousand thirty-one patients were rehospitalized a total of 4,578 times; charges for rehospitalization totaled $23,805,600.00. At least 55% (75% of identifiable weapon and missile injuries) of all charges resulted from handgun injuries. Treating the majority of patients on an outpatient basis and by using selective angiography for extremity wounds, a savings of more than $775,000,000.00 resulted. The potential cost of treating gunshot wounds at a single county hospital was more than $1 billion, or more than $100 million per year. CONCLUSIONS: The costs for hospital treatment of firearm injuries are substantial. A lack of rehabilitation facilities forces prolonged acute hospital admissions in many cases. Avoiding prolonged hospitalization may be helpful in controlling these costs, but will be difficult to achieve. Ninety-six percent of the patients in this report had their costs of care covered by the government, because they had no primary insurance coverage. Primary prevention of firearm injuries, especially those caused by handguns, may be the most effective cost control measure. PMID- 7869456 TI - Histomorphologic changes in keloids treated with Kenacort. AB - Morphologic changes in steroid-treated keloids were established using light and electron microscopy. Attention was directed to the characterization of the tree states of fibroblasts in keloids treated with Kenacort. The probable role of corticosteroids in the regulation of the keloid structure was discussed. PMID- 7869457 TI - Arteriovenous fistula after interlocking nailing of the femur: a case report. AB - The added technical complexity associated with the transfixion screws for interlocking nailing has introduced new complications. We present a case of a femoral arteriovenous fistula caused by the distal interlocking screw after intramedullary nailing of a comminuted diaphyseal femoral fracture. PMID- 7869458 TI - Advances in diagnostics and successful repair of proximal posttraumatic superior mesenteric arteriovenous fistula. AB - Posttraumatic arteriovenous fistulas affecting the superior mesenteric artery and vein are extremely rare. Twenty-four cases of posttraumatic superior mesenteric arteriovenous fistulas (SMAVFs) have been reported. We presented two cases of SMAVFs occurring in a young woman and man secondary to a gunshot and a grenade shrapnel wound in the epigastrium, respectively. Nausea, heartburn, emesis, and cramping abdominal pain were the clinical signs of SMAVF. Abdominal pains, particularly after meals, tense and meteoristic abdomen, frequent liquid bowel movements, oliguria, subfebrility, abdominal thrill, and bruit were also present. Abdominal duplex ultrasonic scanning and computed tomograms with a contrast agent were especially useful screening tools. As our results demonstrated, those methods were not only suitable for clinical use, but were also as good as arteriography in defining both the exact location and the extent of the mesenteric vessel involvement. However, the superior mesenteric arteriogram remains mandatory for complete preoperative evaluation. Arteriovenous fistulas were successfully treated by suturing the arterial and venous sides of the fistula in one case, and resectioning the fistula and end-to-end anastomosis in the other case. PMID- 7869459 TI - Late abdominal complications in war wounded. AB - Complications possibly related to battle injuries are not necessarily discovered immediately postwounding, but may surface many months or years later. Sometimes, the relationship is evident, but often it is difficult to prove the connection. Between 1975 to 1989, we treated 260 veteran wounded from Israel's wars (1948 to 1982). Of these, 122 patients suffered from abdominal complaints, and this study relates only to this group. Eighty percent of them had undergone surgery caused by abdominal trauma at the time of the original injury, and the remaining 20% were injured in areas other than the abdomen. Their complaints manifested several weeks to 35 years postinjury. Diagnosis was delayed for 1 to 8 years in 70% of the patients. Acute or chronic pain, dyspepsia, intolerance to certain foods, early satiety, nausea, vomiting, distension, disturbances in bowel movements, and discharge from unhealed wounds were the most frequently encountered complaints. After evaluation and diagnostic work-up, it was possible to establish diagnosis and afford appropriate treatment in 97 (77%) of the patients. Peptic ulcers were found in 31 patients; 10 required surgery for ulcer-related complications. Acute and repeated attacks of intestinal obstruction occurred in 19 patients; 14 required surgery. The cause of obstruction was adhesions in nine, and strictures, incarcerated hernias, and abscess formation in the rest. Ventral hernias at surgical, ostomy, and drain sites were found and repaired in 49 patients. Abdominal wall sinuses originating from foreign bodies or osteomyelitis were found in 13 patients, and low output enterocutaneous fistulas were found in three patients. Chronic abdominal abscesses were found in 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869460 TI - Brachial artery rupture associated with closed posterior elbow dislocation: a case report and review of the literature. AB - A case report of a closed posterior elbow dislocation with brachial artery rupture treated with a reversed saphenous vein graft, fasciotomy, and medical collateral ligament (anterior oblique component) repair is presented. A literature review of 21 other similar cases is discussed. Three patients were treated with direct arterial suturing, four with ligation, four closed reductions, nine vein grafts, and two were undescribed. Early postoperative complications included anastomosis failure in two patients (9%) and thrombosis in three patients (14%). At final follow-up, 12 patients (55%) had a motor and/or sensory deficit, and 11 patients (50%) had restriction of elbow extension. Seven of these 11 patients had a loss of elbow extension of 5 to 15 degrees; the other four patients had a loss of 20 to 35 degrees. PMID- 7869461 TI - Methadone maintenance counseling. Definition, principles, components. AB - Counseling has been a major service component of methadone maintenance since its inception. Yet, there is no consensus about what methadone counseling is or how it should be practiced. This paper proposes a definition of professional methadone counseling as a specialized modality of addiction therapy and rehabilitation. Five principals of methadone counseling are reviewed: (1) coordination of care, (2) use of the counseling relationship, (3) attention to the stage of recovery, (4) structure and flexibility, and (5) facilitation of patient resourcefulness and social recovery. Fifteen components of methadone counseling are also reviewed. These include interventions focused on (1) the initial phase of treatment, (2) the treatment itself, and (3) the work of rehabilitation. General counseling issues are considered, such as counselor education, the role of the counselor in the program, the methadone controversy, as well as the impact of HIV disease and "crack/cocaine." In closing, the advantages of the proposed model are stressed. PMID- 7869462 TI - Parental relationships and substance use among methadone patients. The impact on levels of psychological symptomatology. AB - The relationship between parental substance use problems (SUPs) and the quality of parental relationships with levels of psychological symptomatology was examined in 155 female and 324 male methadone maintenance patients. Subjects completed the Beck Depression Inventory (BDI), SCL-90, and the Treatment Effectiveness Questionnaire (TEQ), which included questions regarding demographics, drug use, family/social relationships, and substance use in relatives. Of those completing the questionnaire, 40% were randomly selected for an Addiction Severity Index (ASI) interview. As hypothesized, parental SUPs were associated with greater levels of psychological symptomatology, more family/social, and medical problems. Positive parental relationships were associated with significantly lower levels of psychological symptomatology and fewer family/social problems. Males were significantly more likely than females to report positive parental relationships and no parental SUPs. No differences based on race were revealed related to reports of the quality parental relationships or parental SUPs. PMID- 7869463 TI - A menu of potential reinforcers in a methadone maintenance program. AB - This study demonstrates the use of paired comparisons and interval scaling techniques for measuring the relative priority of program privileges available at a methadone maintenance clinic. Fifteen methadone program privileges were combined in all possible pairs (N = 105) on a reinforcer menu and administered to a group of 12 methadone patients and a second group of counselors (N = 4). Data were converted to interval scales using the law of comparative judgment to form a quantitative continuum from least to most preferable. Free methadone, free dental service, and more take-homes were ranked highest in both groups; however, patients showed less differentiation in their preference for these privileges. Dose decreases were least preferred. Results are discussed in terms of their clinical applicability in identifying privileges for potential use in modifying the behavior of drug abusers. The method of paired comparisons has excellent psychometric properties and may offer some advantages over other response scale formats. PMID- 7869464 TI - Financing and cost of standard and enhanced methadone treatment. AB - Although some national surveys of drug-abuse treatment have examined cost and financing issues, our study is one of the first to rigorously analyze the costs and financing of methadone treatment at the program level. Our findings are similar to those found at the national level for treatment cost but deviate significantly from the National Drug and Alcoholism Treatment Unit Survey (NDATUS) findings on funding sources. In addition to examining financing and total cost, we grouped resources into particular categories and examined variations at the client, program, regimen, and setting levels. Our specific findings show that public funding sources overwhelmingly support the programs examined; the average annual cost per client for standard methadone treatment was between $3,750 and $4,400; the marginal cost of providing enhanced treatment was between 5% and 6% of the total annual cost of standard treatment; and the average annual cost at the freestanding community-based programs was significantly different from the average annual cost at the hospital-based treatment program. Our results provide a treatment cost methodology along with a financial profile of treatment operations at three clinics that can be compared across programs and settings. PMID- 7869465 TI - Factors associated with employment among methadone patients. AB - We examined the patient characteristics of 340 subjects in methadone treatment to determine if these characteristics could differentiate among three "stages" of work during the past year (stable unemployment, intermittent work, and stable employment). A multiple discriminant function analysis was able to classify correctly 14% of the cases beyond chance. Results of these analyses found lower depression scores, cocaine abstinence, education, and marital status correlated with stable employment conditions. Interventions designed to change these characteristics may improve employment conditions among methadone patients. PMID- 7869466 TI - Lifetime needle sharing: a predictive analysis. AB - Through understanding predictors of needle sharing, it may be possible to design AIDS prevention interventions more effectively. Data were collected from a sample of 416 patients in two New York City methadone programs in 1990. Questions were asked about needle sharing and about a battery of predictors covering 11 psychosocial domains. Based on factor analysis, these were reduced to seven factors: criminal history, antisocial characteristics, social integration, severity of psychiatric problems, current drug involvement, physical health, and personality disorders. Bivariate analyses showed that criminal involvement, antisocial characteristics, social integration, and age were significantly related to needle sharing. With the seven factors, as well as age, gender, and ethnicity simultaneously examined by means of regression analysis, it was found that criminal involvement, severity of psychiatric problems, and age were all positively associated with needle sharing. Implications for treatment are discussed. PMID- 7869467 TI - Illicit use of methadone among i.v. drug users in Montreal. AB - Few studies have been done on the prevalence of illicit methadone use. Five hundred fifty-nine IV drug users recruited in various ways in Montreal were interviewed concerning their drug use as part of a longitudinal study on HIV infection. Of this number, 133 had heroin as their drug of preference and 426 cocaine. Among the cocaine group, 202 also used heroin. The lifetime prevalence of any illicit methadone use was 59.4% in the heroin group, 26.7% in the cocaine/heroin group, and 3.6% in the cocaine-only group. The 6-month (preceding the interview) prevalence of any illicit use was 42.1%, 6.9%, and 1.3%, respectively, and the prevalence of at least weekly illicit use during that period was 6.3%, 2.0%, and 0%, respectively. The prevalence of illicit methadone use is significant in the population studied. Whether this level of use will be affected by more stringent control on methadone prescription and dispensation remains to be demonstrated. PMID- 7869468 TI - Efficacy of methadone versus methadone and guanfacine in the detoxification of heroin-addicted patients. AB - In a randomized double-blind study, the clinical efficacy of methadone vs. methadone and guanfacine was assessed in terms of evolution of opioid withdrawal symptoms during inpatient detoxification. A total of 144 patients were included and randomly allocated to three different treatment groups: methadone alone, and two combined treatment schedules (methadone plus 3 or 4 mg of guanfacine). No differences were observed among the three groups with regard to retention rate throughout the study period. Both therapies, methadone and methadone plus guanfacine, determined a slight increase in withdrawal scores when methadone was discontinued. However, guanfacine was unable to effectively control methadone associated withdrawal symptoms. These results indicate that guanfacine does not effectively reduce the opioid withdrawal symptoms. PMID- 7869469 TI - Self-reported depression as a predictor of dropout in a hierarchical therapeutic community. AB - Studies of the importance of depression for treatment outcome in hierarchical therapeutic communities are scarce. Therefore, a total of 144 substance abusers consecutively entering Phoenix House in Oslo were followed prospectively through an entire 18-month program. Using a structured interview and two self-report instruments, Million Clinical Multiaxial Inventory and Symptom Checklist-90, 69% of the clients were depressive cases at the time of application. However, depression alone did not predict dropout during the following 1-year inpatient phase. Of the 36 clients who completed the drug-free inpatient year, 19% were depressive cases at this point. Thus being depressed after 1 year increased the risk for dropout five times compared to being nondepressed. The study demonstrates the need for a modification of the treatment model, which might include the use of antidepressant and/or individual psychotherapy, at least in the outpatient phase. PMID- 7869470 TI - HIV antibody testing and client retention in the therapeutic community. A preliminary report of Phoenix House. AB - This report describes the current approach to testing for the human immunodeficiency virus (HIV) antibody at Phoenix House, a large therapeutic community (TC) in the northeastern United States, and presents findings on retention of clients who have been tested for HIV antibodies and notified of their HIV serostatus. A total of 240 clients were tested while in treatment at Phoenix House between April 1988 and July 1992. Of these, 51 tested HIV positive. An additional 76 clients had tested positive for HIV antibodies prior to entering treatment. The difference in length of treatment stay between those who tested negative while in treatment and those who tested positive while at Phoenix House was not significant (t = 0.41, df = 238, p > .683). Although clients who tested seronegative during treatment were found to remain in treatment a significantly longer amount of time than the total population of seropositive clients (t = 4.54, df = 314, p < .001), those who learned of their seropositive status while in treatment remained in the program longer than clients who entered treatment aware of their seropositivity (t = 4.08, df = 125, p < .001). These findings suggest that acute reactions to the knowledge of seropositivity did not determine most premature terminations. The use of a small group, a core technical element of the TC, may have provided a favorable context for the task of HIV counseling and testing. PMID- 7869471 TI - Combined serotonin and dopamine indirect agonists correct alcohol craving and alcohol-associated neuroses. PMID- 7869472 TI - p53 mutations and prognosis in bladder tumors. AB - The incidence of loss of heterozygosity on chromosome 17p and p53 gene mutations was assessed in 43 bladder tumor patients. Histological findings, cigarette smoking and prognosis were examined for possible correlation with the presence or absence of loss of heterozygosity on 17p and p53 mutations. Of 20 informative cases 10 (50.0%) showed loss of heterozygosity of 17p13, including 9 (90.0%) with disease beyond stage pT2. The p53 mutations were detected in 20 of 43 patients (46.5%), including 9 (95.0%) with disease beyond grade 2 and 17 (85.0%) with cancer beyond stage pT2. The incidence of p53 gene mutations was not significantly influenced by habitual smoking but G:C to T:A substitutions, often observed in lung cancers, were detected only in mutations from smokers (5 of 10 or 50%, p < 0.05). Groups with and without loss of heterozygosity showed essentially the same results, while significant differences were found for groups with grades 1 and 2 to 3 (p < 0.05) cancer, stages pT1 and pT2 to 4 (p < 0.01) disease, and with and without p53 gene mutations (p < 0.01, Cox-Mantel test). Genetic alternation in chromosome 17p and p53 mutations would, thus, appear to occur more frequently in high grade and invasive bladder tumors. Cigarette smoking may possibly be a determining factor of mutations of the p53 gene in bladder tumors. Our results indicate that an unfavorable prognostic factor may possibly be linked not only to histopathological findings but the presence of a p53 mutation in bladder tumors as well. Accordingly, mutations of the p53 gene may be deeply involved in late events of tumorigenesis and possibly useful as ideal molecular markers for prognosis in bladder tumors. PMID- 7869473 TI - Laparoscopic marsupialization of the painful polycystic kidney. AB - Autosomal dominant polycystic kidney disease patients may present with intractable cyst pain. Common practice has been to attempt percutaneous drainage of the affected cyst and, if unsuccessful, to offer open surgical decortication. We report laparoscopic renal cyst marsupialization for painful autosomal dominant polycystic kidney disease among 6 patients who failed prior percutaneous drainage. Mean surgical and anesthesia times were 3 hours and 3 hours 35 minutes, respectively. Mean blood loss was 140 cc. Median intervals to ambulation, oral intake and hospital discharge were 1.5, 1.5 and 3 days, respectively. All 6 patients reported pain relief with followup of 6 to 40 months. These results suggest that laparoscopic marsupialization of painful autosomal dominant polycystic kidney disease is technically feasible and safe, and the laparoscopic approach may offer a palliative option for patients in whom prior percutaneous management failed. PMID- 7869474 TI - A trans-reservoir technique for correction of ureterointestinal obstruction in continent urinary diversion. AB - Following construction of a continent colonic urinary reservoir, 5 uretero colonic reimplantations became obstructed at the anastomotic site. In these obstructed units previous percutaneous balloon dilation and stent placement had failed and they were subsequently treated by a new reimplantation procedure. Preoperatively, in all ureteral units a percutaneous ureteral stent was inserted to facilitate intraoperative recognition of the ureteral meatus. The technique included a trans-reservoir approach, which allowed easy localization of the stent and anastomotic site. The ureter was dissected free from the intestinal wall and then was mobilized into the lumen of the reservoir. After excision of the scarred distal ureteral segment and spatulation of the proximal healthy ureter, a new direct mucosa-to-mucosa reimplantation was performed leaving the ureter stented. This trans-reservoir approach (occasionally done through an abdominal transverse muscle splitting incision) allows for shortening of the operation, and avoids the time-consuming and more complicated transabdominal lysis of adhesions. All newly reimplanted ureters (100%) showed evidence of adequate ureteral drainage without residual obstruction on followup excretory urography or furosemide renography up to 45 months postoperatively. The trans-reservoir approach for refractory ureteral reimplantation obstruction in continent colonic reservoirs has been associated with no morbidity or mortality, and facilitates the solution to a difficult clinical problem. PMID- 7869475 TI - Early versus late repair of vesicovaginal fistulas: vaginal and abdominal approaches. AB - We reviewed retrospectively 24 consecutive women who presented with a vesicovaginal fistula repaired by a single surgeon between 1989 and 1993. All patients underwent preoperative investigation, including cystoscopy, excretory urography and bilateral retrograde pyelography. Followup ranged from 6 months to 5 years. Postoperatively, 96% of the women were cured. Two patients had persistent symptomatic detrusor instability and 1 had mild stress incontinence. In 1 woman a vaginal repair failed and she was subsequently cured after an abdominal repair. Five patients presented 6 to 12 months after fistula formation. Among the other 17 patients the average interval from pelvic surgery to vesicovaginal fistula repair was 10.8 weeks. Indications for abdominal repair were indurated vaginal epithelium approximately 2 cm. in circumference around the fistula, a vault fistula with poor vaginal exposure and fistulas involving the ureters. Surgical timing and route of repair are best tailored to the individual patient. PMID- 7869476 TI - Do alpha-blockers have a role in lower urinary tract dysfunction in multiple sclerosis? AB - Lower urinary tract dysfunction is a major cause of morbidity in patients with multiple sclerosis. alpha 1-Adrenergic receptors are present at the bladder neck, where increased tone may be responsible for urinary retention and diminished flow rates. A randomized placebo controlled study was designed to test the hypothesis that blockade of these receptors using the selective alpha 1-adrenergic receptor antagonist indoramin would improve bladder emptying in patients with multiple sclerosis. Peak and mean urinary flow rates, residual volume and symptom score were evaluated at trial entry and again after 4 weeks in 18 men with multiple sclerosis. There was a mean 41% improvement in peak flow rate in the actively treated group compared with a 7.4% deterioration in the placebo group (p < 0.05). Residual volume improved in both groups. Patients taking indoramin reported a greater improvement in urinary symptoms. Modulation of the alpha 1-receptor may have a role in the management of lower urinary tract dysfunction in multiple sclerosis. PMID- 7869477 TI - Experience with repair of hypospadias using bladder mucosa in adolescents and adults. AB - From July 1984 to January 1994, 113 hypospadias operations were performed using a free bladder mucosa graft. There were 31 primary cases and 82 secondary cases in which prior operations had been done. The meatus was penile in 33 patients, penoscrotal in 72 and perineal in 8. The cosmetic and functional results were satisfactory. Postoperative complications included 8 fistulas that required closure and 6 cases of stenosis treated by dilation. Our results suggest that hypospadias repair with a bladder mucosa graft is feasible and reliable. The technique has been performed successfully in the most complex as well as simple cases in adults and adolescents. PMID- 7869478 TI - Indications for urethroscopy in male patients with penile condylomata. AB - Benson et al recommended that to detect condylomata, urethroscopy should be performed on the male partners of women with cervical dysplasia. Considering this, in April 1990 we began to perform urethroscopy on all of our patients who presented with genital condylomata. Between April 1990 and January 1993, 84 patients were referred for initial evaluation of condylomata. The penis, scrotum, perineum and perianal areas were inspected, and the penis was reinspected after staining with 5% acetic acid. Intraurethral condylomata were detected in 13 patients (15%), 11 of whom had visible lesions on physical examination with spreading of the meatus. Urethroscopy confirmed these lesions to be limited to the fossa navicularis. Two patients had lesions of the fossa not visible at the meatus. No patient in this series had lesions of the more proximal urethra. All patients eventually determined to have intraurethral lesions had external condylomata on the distal penis (glans, corona or frenulum). Using the presence of distal penile lesions as the criterion for urethroscopy, 30 patients (36%) would have undergone urethroscopy, including all 13 eventually diagnosed to have intraurethral condylomata, for a yield of 43%. A total of 54 patients (64%) who failed to meet this criterion would have been spared the procedure. Consideration of dysuria or urinalysis did not improve the yield. When evaluating male patients with genital condylomata, we recommend spreading the urethral meatus during the examination. Urethroscopy is indicated only for those with distal penile or meatal lesions. PMID- 7869479 TI - Value of magnetic resonance imaging in patients with penile induration (Peyronie's disease). AB - Magnetic resonance imaging (MRI) is a noninvasive procedure that enables exact imaging of penile anatomy. A total of 34 patients with clinical Peyronie's disease underwent palpation, ultrasound and MRI after intracavernous injection of 10 micrograms. prostaglandin E1. MRI images were obtained before and after intravenous application of gadolinium-diethylenetriaminepentaacetic acid. In 34 patients 45 plaques were palpable. Ultrasound revealed evidence of lesions in 66.6% of the cases. On MRI 36 of 45 palpable plaques (80%) were detected. Not palpable or sonographically revealed indurations could be shown in 4 cases. After intravenous application of gadolinium-diethylenetriaminepentaacetic acid 4 plaques demonstrated contrast enhancement, thus indicating local inflammatory activity. The combination of clinical examination and sonography remains the method of choice for diagnosis and observation of patients with Peyronie's disease. MRI enables exact imaging of penile structures but it does not provide a significant advantage over standard investigative procedures. PMID- 7869480 TI - In vivo assessment of trabecular smooth muscle tone, its application in pharmaco cavernosometry and analysis of intracavernous pressure determinants. AB - A pharmaco-cavernosometry based clinical study was designed to define hemodynamic parameters consistent with complete trabecular smooth muscle relaxation, establish a methodology for overcoming incomplete trabecular smooth muscle relaxation, and determine under controlled conditions the contribution of venous outflow and arterial inflow to the steady-state equilibrium intracavernous pressure. Flow-pressure relationships were analyzed in 21 patients each of whom was assumed to have complete smooth muscle relaxation by virtue of the full, rigid and maintained erectile response following intracavernous vasodilator administration, which required intracavernous adrenergic agonists to achieve detumescence. Flow-to-maintain values increased linearly with intracavernous pressure while venous outflow resistance values were high and constant. Based on these relationships, trabecular smooth muscle tone was assessed in 123 impotent patients. In 14%, 63% and 14% of the patients (112 of 123 overall), respectively, 1, 2 and 3 doses of vasoactive agents were required to achieve hemodynamic relationships consistent with complete trabecular smooth muscle relaxation. In 9% of the patients such hemodynamic relationships were unable to be reached. In the 112 patients the influence of different engineering based measures of corporeal veno-occlusive function, including flow-to-maintain, pressure decay, venous outflow resistance and corporeal capacitance, was analyzed against the spectrum of equilibrium steady-state intracavernous pressures. Two distinct equilibrium pressure groups were identified reflecting different capacitance states: pressures greater than 60 mm. Hg (associated with low capacitance values) and pressures less than 50 mm. Hg (associated with high capacitance values), with pressures 50 to 59 mm. Hg representing a hemodynamic transition zone. When analyzed during complete trabecular smooth muscle relaxation, corporeal veno occlusive hemodynamic variables in conjunction with cavernous arterial perfusion pressure determine the steady-state equilibrium intracavernous pressure. Failure to assess corporeal veno-occlusive function under such conditions will overestimate the degree of suspected corporeal structural disease. PMID- 7869481 TI - Objective quantification of cavernous endothelium in potent and impotent men. AB - Penile corporeal lacunar endothelium is active in the local neural control of corporeal smooth muscle relaxation by producing nitric oxide, a potent vasodilator neurotransmitter. Via computerized image analysis we quantified objectively the percentage of endothelial cells in corpus cavernosum tissues of potent and impotent men. Immunohistochemical staining factor VIII was used to identify the endothelial cells. Five normal potent men had a mean of 2.8% cavernous endothelial cells, compared to 2.4% in 12 patients with venous leakage and 2.8% in 10 with arterial disease. Objective quantification showed no difference in the numbers of cavernous endothelial cells between potent and impotent men. PMID- 7869482 TI - Impotence: expanding the horizons. PMID- 7869483 TI - Systemic sclerosis and impotence: a clinicopathological correlation. AB - A hypothesis of the mechanism of systemic sclerosis associated impotence was developed by making a clinicopathological correlation between the results of preoperative erectile function testing and those of pathological examination of excised erectile tissue in an impotent man with systemic sclerosis. Preoperative examination revealed firm corporeal tissue with diminished penile stretch capability. Pharmacocavernosometry/pharmacocavernosography under conditions consistent with trabecular smooth muscle relaxation revealed severe diffuse corporeal veno-occlusive dysfunction. During penile implantation surgery the compact erectile tissue was unable to be dilated and required sharp corporeal tissue excision under direct vision to achieve cylinder insertion. Histological investigation of the excised corporeal tissue demonstrated severe corporeal fibrosis. Computer assisted color histomorphometry revealed that the mean percentage of trabecular smooth muscle area to total erectile tissue area was 18.2 +/- 13.9% (normal 40 to 52). Immunohistochemical staining with desmin, a protein found in smooth muscle, verified prolific corporeal fibrosis. In situ hybridization of the corporeal tissue demonstrated messenger ribonucleic acid collagen and fibronectin messenger ribonucleic acid expression. Strong hybridization signals were found in mesenchymal cell types, including trabecular smooth muscle cells. In summary, clinicopathological correlation revealed that veno-occlusive dysfunction and loss of penile length were secondary to the excessive accumulation of extracellular matrix, partially due to trabecular smooth muscle cells undergoing synthetic as opposed to contractile phenotypic activity. PMID- 7869484 TI - Organ preserving surgery in testicular epidermoid cysts. AB - Our experience with 18 patients with simple epidermoid cysts of the testis (monodermal teratoma) is reported. In all patients the tumor was enucleated completely and 2 biopsies of the adjacent parenchyma were obtained for exclusion of associated germ cell cancer, scar or carcinoma in situ. There was no evidence of malignancy in any biopsy specimen. Preoperative evaluation included physical examination, testicular sonography, and determination of alpha-fetoprotein and beta-human chorionic gonadotropin levels. Although epidermoid cyst was strongly suggested by sonography, the ultrasonic appearance was not specific and inguinal testicular exploration was required. In 1 patient multiple epidermoid cysts of the right testis were associated with an adult teratoma containing embryonal carcinoma and choriocarcinoma of the left testicle. To our knowledge no similar case has been described in the literature. Based on our results and our experience, we consider tumor enucleation and biopsy of the adjacent parenchyma as adequate treatment for the benign epidermoid cyst. The literature concerning organ sparing surgery in testicular epidermoid cysts is reviewed. PMID- 7869485 TI - Histopathological and cytopathological correlations of percutaneous testis biopsy and open testis biopsy in infertile men. AB - A testis biopsy is used to assess quantitatively testicular spermatogenesis in infertile patients. Recently, several reports have used less invasive, percutaneous methods to obtain testis tissue. Percutaneous testis biopsies and touch imprints, immediately followed by open testis biopsies, were performed on 24 testes (19 patients) to ascertain whether they could provide the same histological information as an open biopsy. The technique of percutaneous testis biopsy using a core biopsy system is described. Comparison of the percutaneous and open biopsy histological diagnoses revealed a 95% correlation. The percutaneous method using 1 pass through the testis failed to provide adequate tissue in 2 of 24 patients. Touch imprints obtained by the percutaneous method also provided a 95% correlation compared with the open method (2 of 24 touch imprints were lost during processing and, thus, were not evaluated). Percutaneous testis biopsies and touch imprints provide adequate tissue for histological and cytological evaluation, with excellent correlation with biopsies obtained by the traditional open methods. Percutaneous testis biopsy and touch imprint may be performed in an office setting, thus obviating the need to perform an open biopsy in the operating room. PMID- 7869486 TI - Delayed appearance of sperm after end-to-side vasoepididymostomy. AB - The frequency and timing of the delayed appearance of sperm following an end-to side vasoepididymostomy were determined in 89 patients. The surgical patency rate, defined as greater than 1 million sperm in the ejaculate, was 56% (50 of 89 consecutive patients). None of the 7 patients without sperm in the epididymal fluid at the anastomosis had sperm in the ejaculate postoperatively. Of the remaining 82 patients 31 had sperm on initial semen analysis within 3 months postoperatively. Seven of the 51 patients whose initial postoperative semen sample revealed azoospermia were lost to followup. Among the remaining 44 patients 18 (41%) had delayed appearance of sperm in the ejaculate (mean delay 6 months, range 3 to 15). The ultimate mean sperm count and motility in the patients with initially positive postoperative semen samples were not significantly different from those in patients with delayed appearance of sperm. In addition, the delayed anastomotic obstruction for both groups was the same (10% and 11%, respectively). Our results demonstrate that delayed appearance of sperm after end-to-side vasoepididymostomy is common and that the prognosis for patients with delayed appearance of sperm is not significantly worse than that for patients with sperm on the initial semen analysis. PMID- 7869487 TI - Surgical techniques for male factor infertility. PMID- 7869488 TI - Bacteriology of urinary tract stones. AB - It has been reported that up to half of renal stones and associated urine specimens have been positive on culture, and that up to 50% of such stones contain magnesium ammonium phosphate. In a prospective study using infrared and wet chemical analysis, we found positive cultures in only 7 of 132 renal, 5 of 105 ureteral and 6 of 21 bladder stones obtained surgically and handled with sterility. Of the culture positive calculi only 43% from the kidney, none from the ureter and 50% from the bladder contained detectable magnesium ammonium phosphate. However, magnesium ammonium phosphate was detectable in 20% of renal, 2% of ureteral and 27% of bladder stones with negative cultures. Of the culture positive renal and ureteral calculi 42% were predominantly calcium phosphate and 17% were predominantly calcium oxalate. For culture negative stones 25% and 51% from the kidney, and 15% and 82% from the ureter were composed of predominantly calcium phosphate and calcium oxalate, respectively. Among the culture positive stones, related positive urine cultures were noted in 100% of the renal, 20% of the ureteral and 50% of the bladder cases, compared to 26%, 10% and 27%, respectively, of culture negative calculi. The same organism was found in the stone and urine in only 38% of the cases. The lower frequency of positive urine cultures, of stones with magnesium ammonium phosphate, and especially of culture positive renal and ureteral stones (5%) than in previous reports suggests that stone culture may be of less value than indicated previously, except for bladder calculi and large renal stones, such as the branched type. PMID- 7869489 TI - Comparison between standard flank versus laparoscopic nephrectomy for benign renal disease. AB - To evaluate the role of laparoscopic nephrectomy in the management of benign renal diseases, 12 patients undergoing laparoscopic nephrectomy were compared to 13 undergoing a classical flank nephrectomy. Both groups were similar in regard to patient age and indications for surgery. The underlying pathological conditions included vesicoureteral reflux, tuberculosis, hydronephrosis, hypertension and failed pyeloplasty. Overall, operative time ranged from 105 to 360 minutes (mean 145) for the laparoscopic group and 60 to 240 minutes (mean 156.6) for the open surgery group. Hospital stay and interval to return to regular preoperative activities were 2 to 6 days (mean 3.5) and 10 to 21 days (mean 16) for patients undergoing laparoscopic nephrectomy, which was significantly shorter than for those undergoing a flank procedure, 3 to 16 days (mean 8) and 35 to 84 days (mean 32.3), respectively. Pain medication requirements were also markedly decreased after laparoscopic nephrectomy. Of the patients in the laparoscopic group 2 experienced complications with only 1 requiring conversion to open nephrectomy. The laparoscopic technique is an effective as the flank approach for benign renal conditions, while providing a more rapid recuperation and superior cosmetic result. PMID- 7869490 TI - Smaller ports result in shorter convalescence after laparoscopic varicocelectomy. AB - Minimal postoperative pain and a shorter convalescence after laparoscopic surgery are attributable to the small puncture wounds produced to accommodate trocars. We investigated the effects of trocar size on convalescence after 37 laparoscopic varicocelectomies. The initial 21 patients underwent the procedure with 2, 10 mm. ports and 1, 5 mm. port, while the last 16 underwent surgery with 3, 5 mm. ports. Postoperative convalescence was evaluated by a questionnaire. The patients who underwent the 5 mm. port technique achieved complete pain relief, returned to work and could resume work at preoperative levels significantly earlier than those who underwent the 10 mm. port technique (2.4 +/- 1.5 days versus 5.9 +/- 4.8 days, p < 0.03; 8.2 +/- 3.1 days versus 10.0 +/- 2.5 days, p < 0.03, and 10.2 +/- 4.4 days versus 14.3 +/- 6.5 days, p < 0.03, respectively). Our study showed that laparoscopic surgery with smaller ports resulted in less postoperative pain and a shorter convalescence than when larger 10 mm. ports were used. PMID- 7869491 TI - Laparoscopic surgery in urology: refining indications and techniques. PMID- 7869492 TI - Placement of large suprapubic tube using peel-away introducer. AB - We describe a new method for placing a large suprapubic tube and report our experience with 56 patients. This method uses a specially designed fascial dilator and peel-away introducer to place an 18F Foley catheter suprapubically. In our experience the method is simple and effective for the exchange of a small suprapubic tube to an 18F Foley catheter, and for primary placement of a large suprapubic tube. It is easily performed at the bedside or during a minor procedure with the patient under local anesthesia. PMID- 7869493 TI - Chart for preparation of dilutions of alpha-adrenergic agonists for intracavernous use in treatment of priapism. AB - Treatment of priapism with intracavernous alpha-adrenergic agonist vasoconstrictor agents is well accepted, particularly for patients with priapism secondary to intracavernous injections of papaverine, phentolamine and/or prostaglandin E1. Although many alpha-adrenergic agonists are commercially available, phenylephrine is preferred because it has potent and selective alpha 1 adrenergic stimulatory properties, which can decrease arteriolar flow to the cavernous sinusoids, and no beta 1-stimulatory effect, which could cause arrhythmias and angina in susceptible patients. Before intracavernous injection or irrigation an alpha-adrenergic agonist must be diluted. However, no readily available reference source lists this information. Therefore, we prepared a chart for extemporaneous preparation of dilutions of alpha-adrenergic agonists for intermittent injection or irrigation. PMID- 7869494 TI - Vesical dysfunction in systemic sclerosis (scleroderma) AB - There have been only a few reports on the involvement of the urinary tract in patients with systemic sclerosis, a disease of the connective tissue characterized by thickening and fibrosis of the skin, abnormality of the small arteries, and involvement of the gastrointestinal tract, heart, lung and kidney. We report the urodynamic assessment and histological examination of 9 women with scleroderma. Three patients voided less than 100 ml. with a significant residual volume and 4 presented with detrusor areflexia during a filling cystometrogram. Histopathological examination in all patients with detrusor areflexia demonstrated the presence of arterial lesions and derangement of the capillary bed of the detrusor musculature. Our data provide evidence for the functional and histological involvement of the bladder in patients with systemic sclerosis. PMID- 7869495 TI - Artificial urinary sphincter in patients following major pelvic surgery and/or radiotherapy: are they less favorable candidates? AB - Between January 1988 and December 1992 the AMS800* artificial urinary sphincter was inserted in 81 men with urinary incontinence due to major pelvic surgery and/or radiation therapy. Radical retropubic prostatectomy had been performed in 38 men, radical retropubic prostatectomy with adjuvant radiation in 28, definitive radiation therapy for prostatic carcinoma in 5, abdominoperineal resection with adjuvant radiation in 1 and radical cystectomy with orthotopic urinary diversion in 8, while 1 suffered major pelvic trauma with urethral rupture. A bulbar urethral cuff was used exclusively, with pressure regulating balloons of 51 to 60 and 61 to 70 cm. water. The interval for primary activation ranged from 4 to 12 weeks (mean 7.7), with all irradiated patients waiting 12 weeks. Surgical revision was required in 38% of the patients totaling 43 operations. Inadequate cuff compression after presumed urethral atrophy secondary to hypovascularity accounted for 74% of the procedures, whereas infection with or without erosion necessitated 8 revisions, mostly attributable to improper placement elsewhere of an indwelling catheter after the artificial urinary sphincter had been activated. Mechanical malfunction was responsible for 7% of the revisions. Overall, socially acceptable continence was achieved in 91% of the study population. Despite a significantly greater need for revision in this high risk group (38% versus 22% in the literature for low risk groups) with meticulous surgical and sterile techniques as well as diligent followup, the long-term outcome in terms of continence and device survival may be excellent regardless of the underlying etiology. We conclude that use of the AMS800 artificial sphincter for significant male urinary incontinence is undoubtedly the most efficacious treatment currently available for which even the most adverse candidate should not necessarily be excluded. PMID- 7869496 TI - Incontinence. PMID- 7869497 TI - Partial adrenalectomy for renal cell carcinoma with bilateral adrenal metastases. AB - Resection of the adrenal glands precludes participation in many immunotherapy protocols for metastatic renal cell carcinoma. We performed radical nephrectomy with adrenalectomy and contralateral partial adrenalectomy, including adrenal vein ligation for a 4 cm. hilar metastasis without perioperative complications or local recurrence after 30 months. Adrenal function, measured by cosyntropin stimulation tests 6 weeks and 10 months postoperatively, was normal. Partial adrenalectomy with preservation of adrenal function is possible. PMID- 7869498 TI - Percutaneous management of renal hydatidosis: a minimally invasive therapeutic option. AB - We report 2 cases of percutaneous drainage and alcohol instillation of renal hydatid cysts. The feasibility of percutaneous management of renal hydatidosis, emphasizing its safety, efficacy and obvious advantages, is discussed. PMID- 7869499 TI - Inverted papilloma of the upper urinary tract. AB - Inverted papillomas of the upper urinary tract are rare lesions that have a male predominance. The associated symptoms are similar to those of other urothelial neoplasms. The tumors are considered benign and local excision has been advocated by many but long-term followup is lacking. We present a case of a locally excised inverted papilloma of the renal pelvis with a 3.5-year followup. While local excision appears to be ideal treatment, the difficulty with preoperative diagnosis and the reported coexistence of malignancy demand careful patient selection and close long-term followup. The biological potential of recurrence, multicentricity and malignancy is addressed. PMID- 7869500 TI - Benign angiomyolipoma involving the renal vein and vena cava as a tumor thrombus: case report. AB - A 53-year-old woman presented with a renal angiomyolipoma extending as a thrombus into the renal vein and vena cava. This case is most unusual and we are unaware of any report of a benign angiomyolipoma that has presented as a tumor thrombus. The intravascular growth of a benign angiomyolipoma has previously been described. PMID- 7869501 TI - A case of unique communication between blind-ending ectopic ureter and ipsilateral hemi-hematocolpometra in uterus didelphys. AB - Uterus didelphys with double vagina and hemi-vaginal atresia is a rare syndrome of congenital anomalies. A 17-year-old girl had a right blind-ending ectopic ureter, the proximal end of which communicated with the ipsilateral uterine cervix of uterus didelphys. The patient presented with vaginal urinary incontinence after incision of the vaginal wall for right hemi-hematocolpometra. Following various examinations, the ipsilateral kidney was found to be absent. The ectopic ureter and communicating duct were resected, and the fistula was closed. The genesis of malformation of the female genitalia and urinary tract resulting in such a unique communication is discussed. The importance of preoperative meticulous examinations, including cysto-genitography, pelvic magnetic resonance imaging and panendoscopy with the patient under anesthesia, is emphasized. PMID- 7869502 TI - Ureteral obstruction due to calculi in the early postoperative period in renal cadaveric transplantation: a case report and discussion of ureteral obstruction in the renal transplant patient. AB - We report a case of obstruction secondary to multiple ureteral calculi on postoperative day 3 after cadaveric renal transplantation. Treatment consisted of ureterolithotomy with stenting of the ureteroneocystotomy and convalescence was otherwise unremarkable. Obstructive complications of the ureter after renal transplantation are reviewed. PMID- 7869503 TI - Extensive dilation of distal ureter for endoscopic treatment of large volume ureteral disease. AB - Two patients with large volume disease in markedly dilated ureters were treated endoscopically by wide dilation of the ureteral orifice and passage of larger nonureteroscopic endoscopes. The larger instruments provided better vision and the ability to work with larger tools, which greatly facilitated treatment without complication in patients who otherwise would have undergone an open procedure. PMID- 7869504 TI - Endocervicosis of the bladder. AB - We report a case of endocervicosis of the bladder. The tumor was successfully resected transurethrally. Histopathology of this rare condition is discussed and the literature is reviewed. The natural course of this entity is poorly documented and close followup is mandatory. When endocervicosis is differentiated confidently from adenocarcinoma, local treatment may be satisfactory. PMID- 7869505 TI - Case of vesico-appendiceal fistula secondary to mucinous adenocarcinoma of the appendix. AB - We present a rare case of vesico-appendiceal fistula secondary to mucinous adenocarcinoma of the appendix. Transurethral biopsy of the bladder revealed a mucinous adenocarcinoma of probable colonic origin. Adenocarcinoma of the appendix that directly invaded the bladder was diagnosed preoperatively by air contrast barium enema, colonoscopy and magnetic resonance imaging. When one encounters a case of adenocarcinoma of the bladder suspected to be of colonic origin, one should examine the colon and rectum as well as the appendix and cecum. PMID- 7869506 TI - Report of a case with giant condyloma (Buschke-Lowenstein tumor) localized in the bladder. AB - Giant condyloma is a variation of condylomata acuminata caused by a sexually transmitted virus infection. Although it is a benign disease, it carries a risk of malignant transformation. Primary locations of giant condyloma are the perianal region and the external genitalia. Bladder involvement is rare. We report on a patient with multiple sclerosis in whom a giant condyloma developed in the bladder. Systemic immunosuppression for the treatment of multiple sclerosis and/or chronic cystitis as a result of neurogenic bladder dysfunction might be a risk factor for the development of giant condyloma of the bladder. PMID- 7869507 TI - Magnetic resonance imaging of the UroLume urethral stent. AB - We discuss the use of magnetic resonance imaging of the pelvis in a patient with the UroLume urethral stent. This case demonstrates that magnetic resonance imaging is a safe and effective modality for imaging tissue surrounding the stent. PMID- 7869508 TI - Condom-related allergic contact dermatitis. AB - After 25 years of wearing a condom catheter, recurrent blisters and epidermal sloughing of the penile shaft developed in a patient. Patch testing revealed hypersensitivities to several allergenic components of the condom catheter (that is thiram and mercaptobenzothiazole). After immediate treatment with topically applied steroids, the condition improved and the patient successfully switched to a silicone condom without further irritation. PMID- 7869509 TI - Penile intracavernous hematoma: diagnosis and surgical considerations. AB - Soft tissue lesions of the penile corporeal bodies are rare and usually represent benign or malignant tumors, or Peyronie's disease. We report a unique case of a deep seated penile mass that at exploration proved to be an encapsulated hematoma of the inter-corporeal septum. Preoperative diagnosis of lesions of the corporeal bodies is facilitated by high resolution Doppler ultrasonography. Surgical exploration to exclude malignancy must be done unless the clinical and/or radiographic findings are unequivocally benign (Peyronie's plaque, simple cyst and so forth). Surgical exploration must be done according to the penile neurovascular anatomy to preserve potency and glanular sensation. PMID- 7869510 TI - Granulomatosis of external genitalia: a new disease or part of a spectrum? AB - Several efforts have been made to classify the various diseases that can cause ulcerative necrosis of the skin and mucous membranes. All of these lesions have granulomatous inflammation as a common denominator. Wegener's granulomatosis belongs to this area of interest. Most of these diseases affect the head, eyes, nose, respiratory system and kidneys. We present a case of ulcerative necrosis with pathological findings of granulomatous inflammation involving the external genitalia, thighs, perineum and eyes. To our knowledge this is the first reported case of involvement of the external genitalia by such a disease. PMID- 7869511 TI - Seminal vesicle urinary reflux as a complication of transurethral resection of ejaculatory ducts. AB - Transurethral resection of ejaculatory ducts has become an effective surgical treatment for male infertility caused by ejaculatory duct obstruction. We report on a patient treated successfully by transurethral resection of the ejaculatory ducts for a large midline cyst who postoperatively complained of terminal urinary dribbling lasting several minutes. On video urodynamic study reflux into and delayed drainage from the right seminal vesicle were found. PMID- 7869512 TI - Nocturnal enuresis provoked by an obstructive sleep apnea syndrome. PMID- 7869513 TI - Duplex ultrasonography after prostaglandin E1 injection of the clitoris in a case of hyperreactio luteinalis. AB - We report an unusual case of persistent postpartum clitorimegaly due to ovarian hyperreactio luteinalis. Duplex ultrasonography of the clitoris after intracorporeal injection of prostaglandin E1 revealed marked clitoral erection and increased arterial flow, as in the penis. PMID- 7869514 TI - Re: Adrenal autografts following bilateral adrenalectomy. PMID- 7869515 TI - Re: Presentation, diagnosis and treatment of renal abscesses: 1972-1988. PMID- 7869516 TI - Re: Stenosis of the afferent antireflux valve in the Kock pouch, continent urinary diversion: diagnosis and management. PMID- 7869517 TI - Re: Patient age as a prognostic factor in prostate cancer. PMID- 7869518 TI - Re: Urinary incontinence due to idiopathic hypercalciuria in children. PMID- 7869519 TI - Hypercalciuria and nephrocalcinosis in the oculocerebrorenal syndrome. AB - The oculocerebrorenal (Lowe) syndrome is an X-linked recessive disorder characterized by congenital cataracts, hypotonia, developmental delay, poor growth and renal tubular dysfunction. Although the disorder has been mapped to chromosome Xq24-26, the underlying metabolic defect remains unknown. The renal component of the Lowe syndrome comprises tubular dysfunction, that is tubular proteinuria and generalized aminoaciduria progressing to the renal Fanconi syndrome, with later glomerular disease. Clinical problems typically include polyuria, acidosis, hypophosphatemia with rickets and eventually end stage renal disease. Hypercalciuria and its sequelae (nephrocalcinosis and nephrolithiasis) have not been described as cardinal features of the untreated disorder although they reportedly complicate vitamin D and calcium therapy of rickets. We discuss 5 boys with congenital cataracts, hypotonia, developmental delay, failure to thrive and the renal Fanconi syndrome who were diagnosed with the Lowe syndrome and in whom hypercalciuria was documented at diagnosis. We conclude that hypercalciuria and its sequelae may occur commonly in patients with the Lowe syndrome as a component of tubular dysfunction or a complication of therapy. PMID- 7869521 TI - Incidence of vesicoureteral reflux in children with unilateral renal agenesis. AB - We retrospectively reviewed 51 pediatric cases of unilateral renal agenesis to determine the incidence of contralateral vesicoureteral reflux. Initial diagnosis of unilateral renal agenesis was made by evaluation of associated congenital abnormality in 21 patients, evaluation of prenatally detected abnormality in 11, evaluation of urinary tract infection in 7, sibling screening in 3, hypertension in 2 and other methods in 7. A voiding cystourethrogram was obtained in 44 cases. Indications for the study included urinary tract infection in 11 patients, hydronephrosis in 18 and screening in 15. Overall, vesicoureteral reflux occurred in 19 of the 51 patients (37%). The highest incidence of contralateral reflux was in those with a prenatal abnormality with or without hydronephrosis (77%) although 5 of 15 patients (33%) who underwent a screening voiding cystourethrogram had reflux. Mean followup was 50 months. Of the patients with vesicoureteral reflux reimplantation was performed in 9, reflux spontaneously resolved in 3 and reflux persisted in 7. There is a high incidence of vesicoureteral reflux in children with unilateral renal agenesis and a voiding cystourethrogram is recommended even in the absence of hydronephrosis or urinary tract infection. Although 50% of children in our series underwent surgical intervention, a period of nonoperative observation is warranted. PMID- 7869520 TI - Retrograde filling of the renal vein on computerized tomography for blunt renal trauma: an indicator of renal artery injury. AB - Assessment of the traumatically injured pediatric patient with computerized tomography has become standard medical practice. We report the unique finding of retrograde flow of intravenous contrast material into the renal vein as a diagnostic indicator of traumatic renal artery injury. With the increasing use of high-speed computerized tomography as the initial study to evaluate and stage blunt abdominal trauma, this finding may assist the physician in the early diagnosis of severe renovascular injury. PMID- 7869522 TI - Contralateral vesicoureteral reflux in children with a multicystic kidney. AB - Multicystic kidneys are commonly diagnosed today due to the widespread use of prenatal ultrasound. Children with a multicystic kidney are at increased risk of contralateral renal abnormalities. We performed a voiding cystourethrogram on 65 children with a newly diagnosed multicystic kidney to determine the incidence of contralateral vesicoureteral reflux. Ten children (15%) with a multicystic kidney had contralateral vesicoureteral reflux, including 8 of 37 boys (22%) and 2 of 28 girls (7%). Contralateral reflux occurred in significantly more white (22%) than nonwhite (4%) patients (p < 0.001). Reflux was grade I in 2 children, II in 2, III in 2, IV in 1 and V in 3. All children were placed on antimicrobial prophylaxis. During a mean followup of 3.1 years grades I and II reflux resolved. Grade III reflux resolved in 1 child and remained stable in 1. Grade IV reflux was downgraded to III in 1 child on prophylaxis. One child with grade V reflux was stable on prophylaxis while the remaining 2 patients underwent ureteroneocystostomy. No child had a urinary tract infection. A significant proportion of white children with a multicystic kidney have contralateral vesicoureteral reflux and initial imaging should include a voiding cystourethrogram. PMID- 7869523 TI - Fertility index analysis in cryptorchidism. AB - We report on 226 male patients with cryptorchidism 6 months to 16 years old who underwent open testis biopsy at orchiopexy or orchiectomy at Children's Hospital and Health Center from 1986 to 1990. A total of 355 specimens was obtained. Tissues were preserved in Bouin's solution and examined on light microscopy for fertility index measurements. Several biopsies prepared using Bouin's preserved paraffinized tissue and glutaraldehyde preserved semi-thin cut tissue were found to have comparable fertility index measurements. Of 184 patients with unilateral undescended testes 87 also underwent biopsy on the contralateral descended testis. A total of 42 patients had bilateral undescended testes. Age matched comparisons were made between fertility index measurements of the undescended testes and those previously reported of normal testes. Additional case matched comparisons of fertility indexes were made in those children who underwent biopsy of the undescended testis and its descended mate. Statistical analysis was performed using the independent Student t-test. When comparing undescended to descended testes, there was no significant difference in the fertility index of patients 1 year old or younger but fertility index differences were statistically significant in all of the other age groups. Fertility index measurements were significantly decreased from normal expected values in all age groups with unilateral cryptorchidism and in all but the 13 to 18-month-old group with bilateral cryptorchidism. The fertility index in the descended testis was similar to previously reported normal testis measurements in boys between 13 months and 6 years old. Our data suggest that potential fertility in the cryptorchid testis may be significantly impaired compared to normal testicular fertility regardless of patient age at the time of discovery of the undescended testis. The fertility index of the descended mates of unilateral undescended testes may also be somewhat impaired in certain age groups. Orchiopexy in the first year of life may be indicate to preserve available fertility potential. PMID- 7869524 TI - Patterns of metastatic spread in prepubertal yolk sac tumor of the testis. AB - Of the 212 patients with yolk sac tumors of the testis registered in the prepubertal testis tumor registry of the American Academy of Pediatrics, Section on Urology, we report on 33 who presented with metastatic disease. Metastases occurred to the retroperitoneum alone in 9 cases, sites consistent with hematogenous spread of disease alone in 13, sites consistent with lymphatic and hematogenous spread in 6, and sites not clearly documented in the registry in 5. These findings, which show a hematogenous predilection in the spread of metastases, suggest that retroperitoneal lymph node dissection has no routine role in the treatment of the child who presents with yolk sac tumor of the testis. PMID- 7869525 TI - Cavernous hemangioma of the scrotum: a rare benign genital tumor of childhood. AB - Cavernous hemangioma is a benign congenital lesion that rarely involves the scrotum and primarily presents during childhood. We report a case of subcutaneous scrotal-perineal hemangioma in a boy initially believed to have an inguinal hernia. These lesions can be diagnostically and therapeutically challenging. Definitive treatment by en bloc excision is recommended. Special staining techniques may be required for accurate pathological diagnosis. PMID- 7869526 TI - Intrascrotal epidermoid cyst with extension into the pelvis. AB - An 8-year-old boy presented with an asymptomatic extratesticular, scrotal epidermoid cyst with extension across the urogenital diaphragm into the pelvis. While routine contrast studies and ultrasound were performed, magnetic resonance imaging was most useful in depicting the anatomical boundaries of the lesion, including the intrapelvic extension. Complete excision was performed transcrotally. The lesion is histologically indistinguishable from epidermoid cysts found elsewhere in the external genitalia, that is the penis, scrotum or testis. The etiology is unknown but it may represent a monolayer teratoma of germ cell origin or abnormal embryological closure of the median raphe. PMID- 7869527 TI - Mixed gonadal dysgenesis and dysgenetic male pseudohermaphroditism. AB - Mixed gonadal dysgenesis and dysgenetic male pseudohermaphroditism are 2 forms of male pseudohermaphroditism that present with absent mullerian regression and ambiguous genitalia. We present a retrospective analysis of 10 patients with the diagnosis of either mixed gonadal dysgenesis or dysgenetic male pseudohermaphroditism encountered during a 16-year period at our institution. We assigned a female gender to 4 patients and a male gender to 3. Three patients were assigned a male gender before referral (2 for whom we would have preferred female assignment). All intra-abdominal gonads were removed except in 2 patients assigned a male gender who underwent bilateral orchiopexy. Patients underwent hypospadias repair or feminizing genitoplasty depending upon the gender assigned. Although female gender assignment is usually preferred, male assignment is a justifiable alternative in instances of extreme virilization and a descended testis. However, in these male assigned patients, consideration must be given to the role of periodic testicular biopsies. In light of tumor potential, all intra abdominal gonads should be removed. When necessary, appropriate surgical genitoplasty should be performed at an early patient age. PMID- 7869528 TI - Volume expansion enhances the recovery of renal function and prolongs the diuresis and natriuresis after release of bilateral ureteral obstruction: a possible role for atrial natriuretic peptide. AB - Plasma atrial natriuretic peptide (ANP) levels are elevated in patients with bilateral ureteral obstruction (BUO). To further evaluate the role of ANP in postobstructive diuresis, natriuresis and recovery of renal function, 3 groups of dogs were studied: Group 1, 6 dogs that underwent 48 hours of unilateral ureteral obstruction (UUO); Group 2, 6 dogs that underwent 48 hours of BUO; and Group 3, 6 dogs volume replete with normal saline during 48 hours of BUO. All 3 groups underwent hourly hemodynamic and clearance studies for 15 hours after the release of obstruction. Group 1 experienced no increase in either urine output or sodium excretion from the ipsilateral or contralateral kidney after release of obstruction. Groups 2 and 3 both experienced an initial diuresis and natriuresis after BUO (p < 0.01). However, in Group 2 diuresis and natriuresis after BUO ceased at 5 and 2 hours, respectively, while in Group 3 both persisted for 10 and 9 hours, respectively. Before obstruction the GFR was similar in all three groups. In Group 1 the GFR decreased significantly in the ipsilateral kidney (34.5 +/- 1.4 to 14.48 +/- 1.5 ml. per minute, (p < 0.01)) and increased significantly in the contralateral kidney (32.4 +/- 2.8 to 44.4 +/- 2.0 ml. per minute, (p < 0.05)) and remained so throughout the postobstruction period. The GFR in Groups 2 and 3 decreased to a similar level 1 hour after release (13.3 +/- 1.7 and 17.5 +/- 3.4 ml. per minute, respectively); however, Group 2 remained decreased during the period after release while group 3 increased to 23.4 +/- 3.4 ml. per minute (p < 0.01) at 11 hours after release of obstruction. In Group 2 the control plasma ANP level was 17.9 +/- 3.7 pg./ml. and was not altered by BUO, whereas ANP increased significantly after 48 hour BUO in Group 3, from 30.6 +/- 6.7 to 63.7 +/- 11.7 pg./ml. (p < 0.01). Before and after 48 hours of BUO, the pulmonary capillary wedge pressure was 5.0 +/- 2.0 mm. Hg and 7.0 +/- 1.0 mm. Hg (NS) in Group 2, while it increased from 7.18 +/- 1.5 mm. Hg to 11.6 +/- 1.9 mm. Hg (p < 0.01) in Group 3. We conclude that volume expansion during BUO enhances postobstructive diuresis and natriuresis and allows a greater recovery of GFR after release of the obstruction. This effect may be mediated through elevated plasma levels of ANP as measured in this study. PMID- 7869529 TI - Vasectomy in the rat--effects on mineral metabolism, with emphasis on renal tissue minerals and occurrence of urinary stones. AB - An increased stone frequency and hypotestosteronemia after vasectomy were reported and suggest development of some disturbance of homeostasis of minerals and hormones. The objective of the present study in the rat was to assess the effects of vasectomy (n = 14) and vasovasostomy (n = 12) on gonadal state, intestinal absorption of minerals and mineral concentrations in serum, urine and 3 renal tissue regions. Sham-operated animals (n = 12) served as controls. Seven months after surgery the combined results show that vasectomy induced a significant decrease in gonadal weight, but not in serum and urinary testosterone; serum magnesium was decreased (p = 0.014 versus controls) and phosphaturia was increased (p = 0.025), whereas serum calcium, parathyroid hormone and urinary cyclic AMP were unchanged. Also, after vasectomy there was a significant accumulation of phosphorus, calcium and magnesium in renal papillae and additionally of phosphorus in the renal cortical and medullary region; oxalate was unchanged. Renal stones containing calcium phosphate were found in 2 vasectomized rats, but in none of the vasovasostomized ones. In contrast, in vasovasostomized rats, mineral accumulation in renal tissues was abolished, and the associated concentration of serum free testosterone was 3 times higher (p = 0.018) than in control rats. It was concluded that vasectomy in the rat 1) may not be neutral to gonadal function in terms of gonadal weight; 2) disturbs the homeostasis of magnesium, calcium and phosphorus at the level of the kidney; and 3) induces mild hypomagnesemia and marked hyperphosphaturia in the presence of normal parathyroid gland function. It is suggested that these sequelae of vasectomy and vasovasostomy may be traced back to a disturbance of autonomous nerve tone. PMID- 7869530 TI - Effect of mucosal removal on the response of the feline bladder to pharmacological stimulation. AB - The urothelium plays an important role in the maintenance of normal bladder function. It provides a nonpermeable barrier to the contents of urine. The urothelium is directly involved in the transduction of both intravesical pressure and intravesical volume information to the afferent nerve fibers located within the lamina propria area. A third function may be to modulate bladder contractile function through local secretion of bioactive substances into the muscularis layers adjacent to the urothelium. To test this last hypothesis, the following experiments were performed: Strips of female cat bladders were isolated from the bladder body, base and urethra. The mucosa of alternate adjacent strips was removed, and the contractile response to field stimulation (FS), bethanechol (body), phenylephrine (base, urethra) and KCI was determined. For the bladder body, the strips without mucosa responded to FS, bethanechol, adenosine triphosphate (ATP) and KCI significantly greater than the strips with mucosa intact. For the bladder base and urethra, the contractile responses to FS, KCI and phenylephrine were significantly greater for the strips with mucosa removed as compared with the strips with mucosa intact. For the urethra and bladder base, FS in the presence of phenylephrine produced a relaxation. For the bladder base, the degree of FS relaxation of the isolated strips with mucosa removed was significantly greater than the strips with mucosa intact. For the urethra, FS relaxation was similar for the two groups. In conclusion, removal of the urothelium significantly and substantially increased the contractile response to FS, KCI, bethanechol and phenylephrine. Field stimulation relaxation in the bladder base was also enhanced. Thus in the cat, the mucosa has a significant inhibitory effect on the contractile response of the bladder to stimulation. The mechanism of this activity is not clear at the present time but will be the subject of further study. PMID- 7869531 TI - Effect of piezoelectric energy on porcine kidneys using the EDAP LT.02. AB - EDAP International (Cambridge, Massachusetts) has developed a new piezoelectric lithotripter (LT.02) that differs from their earlier model (LT.01) in two important respects: method of stone visualization and available power. The LT.02 provides both in-line fluoroscopy as well as real time ultrasound. The maximum energy is 1400 Bar (compared with 1100 Bar in the LT.01). The purpose of this study was to determine whether treatment with the EDAP LT.02 piezoelectric lithotripter would cause significant renal injury in minipigs. Accordingly, 18 minipigs were divided into 3 groups of 6. Each group received a treatment of 20, 40 or 60 minutes; the power level and shock wave frequency were kept at maximal levels throughout the treatment period. Three pigs from each group were sacrificed at 72 hours (acute). The remaining 9 pigs were sacrificed 1 month following LT.02 treatment (chronic). Histopathologic analysis of the treated kidney revealed that 33% of the 9 acute pigs developed a small capsular hematoma, whereas 66% showed only a small parenchymal contusion ( < or = 1% of total renal volume). Among the chronic pigs, 66% had a small cortical scar, whereas 33% had no macroscopic pathology. Despite the differences in the number of shock waves delivered, these changes were evenly distributed among the 3 groups. Histologic acute changes included circumscribed areas of hemorrhagic infarction, vascular thrombosis with recanalization and focal tubular obstruction and damage. At 30 days, however, these acute injuries had completely resolved in 3 pigs and were only notable as minute areas of focal tubular loss in 6 pigs. PMID- 7869532 TI - Sutureless rabbit bladder mucosa patch graft urethroplasty using diode laser and solder. AB - Fistula and strictures at the site of sutured anastomoses are frequent complications of major urethroplasty. We harvested bladder mucosa in 26 rabbits to repair large defects in the proximal urethra using laser-activated solder in the hope that such a repair would be stronger, faster to create and avoid common complications seen with conventional repair. Large oval defects were created in the proximal urethra in all animals undergoing urethroplasty. Twelve animals underwent bladder mucosa graft closure via diode (808 nm.) laser activation of an albumin-based solder (50% were suture-free). Fourteen additional animals underwent closure with 7-zero polydiaxanone suture (controls). Leak pressure and time of repair were recorded for each graft. Additional sections of bladder mucosa were harvested, transected and repaired by laser welding to determine tensile strength. In both groups, radiography, urethroscopy and clinical course were evaluated for as much as 6 weeks postoperatively. Urethroplasty time was significantly (p < 0.01) shorter for the laser group (13.8 +/- 2.5 minutes) than for the sutured repair group (24.0 +/- 5.3 minutes). Initial leak pressures for the lasered grafts averaged at least 4 times those of sutured grafts (p < 0.01). The tensile strength for lasered bladder mucosa was 3.16 +/- 1.12 kg./cm.2 Early retrograde urethrograms (RUG) performed at 7 days (n = 5) revealed urinary extravasation and fistula formation in 2 control animals compared with a normal urethral appearance in 3 lasered repairs. Early retrograde urethrograms performed at 21 days (n = 21) demonstrated smooth-walled urethras with no evidence of fistula, stricture, or urinary extravasation in the lasered group; varying degrees of reactive mucosal proliferation were seen in the controls. Urethroscopy confirmed these observations. At 6 weeks, histologic examination confirmed the presence of viable graft in all animals. We conclude that bladder mucosa patch graft urethroplasty using diode laser welding and albumin-based solder is an attractive alternative to conventional methods. PMID- 7869533 TI - Inhibition of central sympathetic and somatic outflow to the lower urinary tract of the cat by the alpha 1 adrenergic receptor antagonist prazosin. AB - Selective alpha 1 adrenergic receptor antagonists are used to reduce the dynamic component of urethral obstruction in patients with benign prostatic hyperplasia. Their effectiveness is presumed to result from blockade of alpha 1 adrenergic receptors within the prostatic smooth muscle. However, a reduction in central sympathetic tone to the prostate might also contribute to their effectiveness. The present experiments examined the effects of the selective alpha 1 adrenergic receptor antagonist prazosin on sympathetic activity recorded from the hypogastric nerve in chloralose-anesthetized cats. For comparison, the effects of prazosin were also examined on somatic activity recorded from the pudendal nerve. When the urinary bladder was empty, prazosin reduced spontaneous activity recorded from the hypogastric nerve (to 65% of control) and reduced evoked reflex activity recorded from the hypogastric nerve (to 44% of control) and the pudendal nerve (to 48% of control). Interestingly, when the urinary bladder was filled, the inhibitory effects of prazosin on the pelvic to hypogastric reflex were overcome. These experiments indicate that central noradrenergic neurons mediate a tonic facilitation of sympathetic and somatic activity to pelvic viscera via activation of alpha 1 adrenergic receptors. Thus, alpha 1 adrenergic receptor antagonists may reduce the dynamic component of urethral outlet obstruction in patients with benign prostatic hyperplasia through dual mechanisms: first, through a blockade of alpha 1 adrenergic receptors on the prostatic smooth muscle itself and, second, by reducing the activity of the sympathetic neurons that innervate the prostate. Additional therapeutic relief may be provided through reduction of somatic neural activity to the external urethral sphincter, which might also reduce outlet resistance and improve flow. PMID- 7869534 TI - The effect of unilateral injury to the vas deferens on the contralateral testis in immature and adult rats. AB - The relationship between alterations in testicular histology and antisperm antibodies in immature and mature Lewis rats subjected to unilateral vasectomy was studied. Forty percent of immature rats and 90% of mature rats (p < 0.01) demonstrated significant alterations in both the obstructed (vasectomy) testis and the contralateral testis. There were significant changes in antisperm antibodies (ELISA) in the animals which demonstrated histologic changes. PMID- 7869535 TI - Testicular injury induces cell-mediated autoimmune response to testis. AB - Studies on testis autoimmunity are needed for a better understanding of immunological male infertility. Evidence has accumulated that the delayed type hypersensitivity (DTH) response plays a key role in the induction and/or maintenance of experimental autoimmune orchitis (EAO), an animal model for human immunological male infertility or aspermatogenesis. We report here that an antigen-specific DTH response to autologous testicular cells (TC) could be induced by bilateral testicular injury (trauma) in mice. Pretreatment of traumatized mice with a high dose of cyclophosphamide (CY) enhances the DTH response in a dose-dependent manner. The DTH response induced by testicular injury reaches its peak on the ninth day. We have shown that the local passive transfer of the footpad reaction to normal recipients by T cells further defines the DTH reaction. These characteristics resemble those of the previously reported DTH response to syngeneic TC induced by subcutaneous immunization with viable syngeneic crude TC. Our present injury model mimics clinical testicular trauma; therefore, this testicular injury model can be very useful in studying the immunological mechanism of EAO and of human immunological male infertility. PMID- 7869537 TI - Molecular epidemiology of catheter-associated bacteriuria in nursing home patients. PMID- 7869536 TI - Dormant microbes in interstitial cystitis. AB - Interstitial cystitis (IC) is an inflammatory disease of the urinary bladder that has no known etiology. A microbial association with this disease has not been supported since routine cultures of urine from IC patients are usually negative. However, we have demonstrated the presence of bacterial 16S rRNA genes in bladder biopsies from 29% of patients with IC, but not from control patients with other urological diseases. The ability to identify the presence of bacterial DNA in these patients was accomplished using a sensitive and specific nested PCR method capable of amplifying 16S rRNA genes from a wide variety of bacterial genera. Cloning and sequencing of 16S rRNA gene fragments amplified from bladder tissue of IC patients showed that these genes were derived from genera representing Gram negative bacteria. In addition to the molecular data, a novel finding of 0.22 micron. filterable forms has been isolated in culture from the biopsy tissue of 14 of 14 IC patients and from 1 of 15 controls. The forms contain nucleic acids and resemble cell wall-deficient bacteria in gross morphology; however, their swirled myelin-like ultrastructure is unusual and suggests a heretofore unclassified microbe. These results demonstrate for the first time an association of Gram-negative bacterial DNA and filterable forms with affected bladder tissue from patients with IC. PMID- 7869538 TI - A piece of my mind. Beginnings. PMID- 7869539 TI - Cancer gene patent dispute settled. PMID- 7869540 TI - Lengthy tale of varicella vaccine development finally nears a clinically useful conclusion. PMID- 7869541 TI - Gynecologic oncologists optimistic about diagnosis, therapy gains from reported research. PMID- 7869542 TI - From the Centers for Disease Control and Prevention. Trends in sexual risk behavior among high school students--United States, 1990, 1991, and 1993. PMID- 7869543 TI - From the Centers for Disease Control and Prevention. Update: influenza activity- New York and United States, 1994-95 season. PMID- 7869544 TI - From the Centers for Disease Control and Prevention. Dengue type 3 infection- Nicaragua and Panama, October-November 1994. PMID- 7869545 TI - From the Centers for Disease Control and Prevention. Indicators of nicotine addiction among women--United States, 1991-1992. PMID- 7869546 TI - The quality of quality-of-life measurements. PMID- 7869547 TI - The quality of quality-of-life measurements. PMID- 7869548 TI - The quality of quality-of-life measurements. PMID- 7869549 TI - The quality of quality-of-life measurements. PMID- 7869550 TI - Testing for BRCA1 in hereditary breast cancer. PMID- 7869551 TI - Possible morbidity in women from talc on condoms. PMID- 7869552 TI - Lead poisoning deaths in the United States, 1979 through 1988. PMID- 7869553 TI - Prophylaxis against Pneumocystis carinii pneumonia at higher CD4+ T-cell counts. PMID- 7869555 TI - HIV transmission through donor artificial insemination. AB - OBJECTIVE: To investigate and report cases of human immunodeficiency virus (HIV) transmission through donor artificial insemination (AI) before 1986 at five infertility clinics. DESIGN: Two types of look-back studies were performed: (1) identification of an HIV-infected woman who reported previous AI, followed by identification of the infected donor(s) and contact tracing of women who were inseminated with his semen, and (2) identification of an HIV-infected donor and subsequent examination of women receiving AI procedures using his semen. SETTING: Five infertility clinics in Los Angeles County, California; San Diego County, California; Arizona; and Vancouver, British Columbia. PATIENTS: A total of 230 women were inseminated with semen from any one of the five identified HIV infected donors; 199 (87%) consented to HIV testing. MAIN OUTCOME MEASURE: Seropositivity for HIV among AI recipients. RESULTS: Seven (3.52%) of the 199 women (95% confidence interval, 1.55% to 7.41%) who were artificially inseminated with semen from any of five HIV-infected donors and consented to HIV testing tested HIV-seropositive. Information on HIV risk was available for three of the five donors; all three reported a history of having sex with men. Four HIV infected women were identified through uncommon circumstances, rather than through routine look-back studies of donors. CONCLUSION: Infection with HIV through donor AI performed before routine HIV screening of semen donors represents a potentially serious threat to women who underwent AI procedures. Public health policies requiring retrospective identification of HIV-infected semen donors and patients receiving AI before 1986, especially in acquired immunodeficiency syndrome (AIDS)-prevalent areas, should be considered routine. Women diagnosed with AIDS or HIV infection, in whom no identified risk of HIV acquisition is established, should be questioned about previous AI procedures. PMID- 7869554 TI - Interchangeability of conjugated Haemophilus influenzae type b vaccines in infants. AB - OBJECTIVE: To evaluate the safety and immunogenicity of two Haemophilus influenzae type b (Hib) conjugate vaccines when administered in serial combination. These vaccines consisted of Hib capsular polysaccharide polyribosyl ribitol phosphate (PRP) conjugated to the meningococcal outer membrane protein (OMP) complex (PRP-OMP) and H influenzae oligosaccharide conjugated to a mutant toxin (CRM197) isolated from Corynebacterium diphtheriae (HbOC). DESIGN: Randomized, double-blind, clinical trial evaluating five Hib vaccination regimens. SETTING: Vaccine Treatment and Evaluation Units and affiliated private pediatric practices at Saint Louis (Mo) University, Vanderbilt University, Nashville, Tenn, and Baylor College of Medicine, Houston, Tex. PATIENTS: A total of 497 healthy 2-month-old infants scheduled to receive routine immunization. INTERVENTION: Participants received either PRP-OMP or HbOC given as recommended by the manufacturer, PRP-OMP at 2 and 6 months, HbOC at 2 months, then PRP-OMP at 4 and 6 months, or PRP-OMP at 2 months and then HbOC at 4 and 6 months. Unconjugated PRP was given at 15 months to evaluate priming. RESULTS: Geometric mean antibody concentrations differed significantly among the groups following the second and third immunizations of the primary series and following booster immunization with unconjugated PRP. On each occasion, the groups receiving serial combinations of PRP-OMP and HbOC achieved mean antibody concentrations that equalled or exceeded those of the groups receiving a single product. Adverse reactions did not vary by group. CONCLUSIONS: The studied sequential combinations of Hib vaccines were safe and at least as immunogenic as either vaccine alone. PMID- 7869556 TI - Risk factors for primary invasive pneumococcal disease among children in Finland. AB - OBJECTIVE: To study risk factors for invasive pneumococcal disease among children. DESIGN: A population-based, case-control study of 149 cases and 284 controls matched for age, sex, and place of residence. SETTING: Finland, November 1986 through November 1989. PATIENTS AND CONTROLS: Patients were identified from a prospective nationwide surveillance for invasive bacterial diseases among children (0 to 15 years of age) through a network of bacteriologic laboratories. Two matched controls were selected for 135 of the cases and one matched control for 14 of the cases from the respective cases' child health center or school. Questionnaires evaluating potential risk factors were mailed to families of cases and controls. RESULTS: An increased risk for invasive pneumococcal disease among children younger than 2 years was associated with day care center attendance (odds ratio [OR] = 36; 95% confidence interval [CI], 5.7 to 233), family day care (OR = 4.4; 95% CI, 1.7 to 12), and history of frequent otitis media (OR = 8.8; 95% CI, 2.5 31). For those at least 2 years of age, existence of siblings younger than school-age indicated increased risk for invasive pneumococcal disease (OR = 2.2; 95% CI, 1.1 to 4.4). CONCLUSIONS: Day care center attendance is a major risk factor for invasive pneumococcal disease for children younger than 2 years, with significantly higher risk than the risk associated with family day care. PMID- 7869557 TI - Pressure ulcer risk factors among hospitalized patients with activity limitation. AB - OBJECTIVE: To identify specific demographic, medical, functional status, and nutritional characteristics that predict the development of stage 2 or greater pressure ulcers among patients whose activity is limited to bed or chair. DESIGN: Prospective inception cohort study. SETTING: Tertiary care, urban, university teaching hospital. PATIENTS: A total of 286 patients fulfilling the following criteria: admitted to the hospital within the previous 3 days, age 55 years or more, expected to be confined to bed or chair for at least 5 days or had a hip fracture, and without a stage 2 or greater pressure ulcer. MAIN OUTCOME MEASURE: Time to in-hospital development of a stage 2 or greater pressure ulcer. RESULTS: Total cumulative incidence of pressure ulcers was 12.9% (n = 37) after a median time of 9 days from admission to final skin examination. Age of 75 years or more, dry skin, nonblanchable erythema (a stage 1 pressure ulcer), previous pressure ulcer history, immobility, fecal incontinence, depleted triceps skinfold, lymphopenia (lymphocyte count < 1.50 x 10(9)/L), and decreased body weight (< 58 kg) were significantly associated with pressure ulcer development by univariate Kaplan-Meier survival analyses (P < .05 by log-rank test). Risk ratios (and 95% confidence intervals) for predictors (P < or = .05) of pressure ulcer development after multivariable Cox regression analysis included the following: nonblanchable erythema, 7.52 (1.00 to 59.12); lymphopenia, 4.86 (1.70 to 13.89); immobility, 2.36 (1.14 to 4.85); dry skin, 2.31 (1.02 to 5.21); and decreased body weight, 2.18 (1.05 to 4.52). The 3-week cumulative incidence of pressure ulcers with none, one, two, or three or more of these characteristics was 0%, 11.4%, 39.6%, and 67.9%, respectively (P < .001 by log-rank test). CONCLUSIONS: These results suggest that nonblanchable erythema, lymphopenia, immobility, dry skin, and decreased body weight are independent and significant risk factors for pressure ulcers in hospitalized patients whose activity is limited to bed or chair. PMID- 7869558 TI - Placing trials in context using Bayesian analysis. GUSTO revisited by Reverend Bayes. AB - Standard statistical analyses of randomized clinical trials fail to provide a direct assessment of which treatment is superior or the probability of a clinically meaningful difference. A Bayesian analysis permits the calculation of the probability that a treatment is superior based on the observed data and prior beliefs. The subjectivity of prior beliefs in the Bayesian approach is not a liability, but rather explicitly allows different opinions to be formally expressed and evaluated. The usefulness of this approach is demonstrated using the results of the recent GUSTO study of various thrombolytic strategies in acute myocardial infarction. This analysis suggests that the clinical superiority of tissue-type plasminogen activator over streptokinase remains uncertain. PMID- 7869559 TI - Transplantation milestones. Viewed with one- and two-way paradigms of tolerance. PMID- 7869561 TI - The sensitive heart. A syndrome of abnormal cardiac pain perception. PMID- 7869560 TI - Cardiac demands of heavy snow shoveling. AB - OBJECTIVE: To assess the physiologic responses to manual (shoveling) vs automated (electric snow thrower) snow removal in healthy, untrained men. DESIGN: Observational, controlled trial. SETTING: A community-based, acute care, teaching research hospital. PARTICIPANTS: A volunteer sample of 10 apparently healthy untrained men (mean +/- SD age = 32.4 +/- 2.1 years) met all eligibility criteria and completed the study. INTERVENTION: Each subject cleared two 10 +/- 2-cm-high, 15-m-long tracts of heavy, wet snow in the cold (2 degrees C), using self-paced manual and automated methods, in random order, with 10- to 15-minute rest periods between each 10-minute bout of work. MAIN OUTCOME MEASURES: Heart rate, blood pressure, oxygen uptake, and perceived exertion during snow removal were compared with values obtained during maximal arm-ergometer and treadmill tests. RESULTS: Mean heart rate during shoveling was 154 and 173 beats per minute at 2 and 10 minutes, respectively, corresponding to 86% and 97% of maximal heart rate. Relative heart rate (percentage of maximal heart rate) during shoveling was inversely related to aerobic fitness (r = -0.65; P = .05). The highest heart rate and perceived exertion responses during shoveling, arm-ergometer, and treadmill testing were comparable. Systolic blood pressure during snow shoveling (198 +/- 17 mm Hg) was significantly greater (P < .003) than during arm ergometry or automated snow removal and slightly greater than during maximal treadmill testing (181 +/- 25 mm Hg). Oxygen uptake during shoveling was similar to that for arm ergometry (5.7 vs 6.3 metabolic equivalents), but lower than for treadmill testing (9.3 metabolic equivalents). Cardiorespiratory and perceived exertion responses were reduced during automated snow removal. CONCLUSION: Heavy snow shoveling elicits myocardial and aerobic demands that rival maximal treadmill and arm-ergometer testing in sedentary men. These responses may contribute to cardiovascular events reported after heavy snowfalls. PMID- 7869562 TI - Lot-release criteria, postlicensure quality control, and the Haemophilus influenzae type b conjugate vaccines. PMID- 7869563 TI - Artificial insemination by donor. Safety and secrecy. PMID- 7869564 TI - And then there were none. The demise of national medical television. PMID- 7869565 TI - Home administration of allergen extracts. PMID- 7869566 TI - Evaluation of alopecia. PMID- 7869567 TI - Dietary therapy in type II diabetes mellitus. PMID- 7869568 TI - IARC working group on the evaluation of carcinogenic risks to humans: some industrial chemicals. Lyon, 15-22 February 1994. PMID- 7869569 TI - Propylene. PMID- 7869570 TI - Propylene oxide. PMID- 7869571 TI - Isoprene. PMID- 7869572 TI - Styrene. PMID- 7869573 TI - Styrene-7,8-oxide. PMID- 7869574 TI - 4-vinylcyclohexene. PMID- 7869575 TI - 4-vinylcyclohexene diepoxide. PMID- 7869576 TI - Vinyl toluene. PMID- 7869577 TI - Acrylamide. PMID- 7869578 TI - N-methylolacrylamide. PMID- 7869579 TI - Methyl methacrylate. PMID- 7869580 TI - Ethylene. PMID- 7869582 TI - Ethylene oxide. PMID- 7869581 TI - 2-ethylhexyl acrylate. PMID- 7869583 TI - [The 36th Congress of the Japanese Society of Clinical Hematology. Tokyo, Japan. November 8-10, 1994. Abstracts]. PMID- 7869584 TI - [Development and application of non-radio isotropic PCR-SSCP analysis for genetic diagnosis]. AB - We applied a new and powerful technique for genetic diagnosis, so called reverse transcript-polymerase chain reaction-single strand conformation polymorphism (RT PCR-SSCP) without using radio labeled materials (non-RI). The principle of this method is mobility shift analysis of single-stranded DNAs on neutral polyacrylamide gel electrophoresis to detect DNA polymorphisms. Like restriction fragment length polymorphisms (RFLPs), SSCPs were found to be allelic variants of true Mendelian traits. In this study, this method was used to determine the mutations of the LDL receptor or insulin receptor. We found new mutations in Exon 14 of the LDL receptor, and a patient had a new missense mutation in which Asn461 was substituted for Thr461 in the alpha-subunit of the insulin receptor. Our findings indicate that this analysis can be successfully used to not only rapidly and easily but also safely screen mutation containing exons in large genes, compared to the conventional Southern blotting analysis. Moreover, this analysis has the advantage over the RFLP analysis that it can detect DNA polymorphisms and point mutations at a variety of positions in the DNA fragments. This "non-RI" RT PCR-SSCP analysis is expected to be useful as a routine examination for genetic diagnosis in the ordinary laboratory. PMID- 7869585 TI - [Why should we measure MIC?]. AB - In actual infectious diseases, bacterial invasion and the effect of antibiotics show "dynamic" behavior, being continuously influenced by various factors. Therefore, "some" knowledge and experience are essential to treat a patient and to make an appropriate decision through only limited information. On the other hand, many patients today still die of infection at the terminal state of illness. Therefore, the importance of "clinical microbiology" has not faded away at all, and will increase much more in the future. However, medical students are not well taught "drug-dynamics" and "how to perform empiric therapy" in the under graduate curriculum. Thus, such knowledge must be obtained by "self-effort"; i.e., why MIC should be measured, how to make use of MIC for treatment, what the most important information upon treatment of infection is, what moiety is not reflected by MIC, how to judge from which point of MICs, and so on. Furthermore, education or guidance in such fields are not always provided even in the post graduate training course. To solve these difficulties, we originated a new computer system supporting antimicrobial chemotherapy, which has actually been working well in our hospital from May of 1994. This system is intended to convey maximally the "meaning" of the test results, instead of just reporting only "prosaic" results. In this system, detailed information on various kinds of bacteria and antibiotics is immediately available on every computer monitor. Furthermore, the data base on the average concentration of various antibiotics expected to be reached in each organ by every dose method is already in the system. When MIC actually measured is larger or smaller than such a value, a signal of "untreatable" or "treatable" will appear on the monitor. This is an epoch-making system in Japan, and will help the physicians to provide effective therapy. PMID- 7869586 TI - [Molecular typing of the methicillin resistance determinant (mec) of clinical strains of Staphylococcus based on mec hypervariable region length polymorphisms]. AB - We used a method for molecular typing of the methicillin resistance determinant (mec) based on the size of the mec-associated hypervariable region amplified by the polymerase chain reaction (PCR) to examine 106 methicillin-resistant Staphylococcus aureus (MRSA), 9 methicillin-resistant (Mcr) S. epidermidis and 5 Mcr S. haemolyticus clinical isolates. In the 106 MRSA isolates, 5 sizes of PCR products were observed. The MRSA isolates were grouped into five hypervariable region (HVR) genotypes on the basis of the size of the PCR product. The PCR products amplified from 8 of 9 Mcr S. epidermidis isolates were the same as products amplified from MRSA isolates, which was confirmed by the PCR-SSCP (single-strand conformation polymorphism) method. In 32 methicillin-susceptible isolates, the target gene was not amplified. This method is thought to be useful in epidemiological investigations of nosocomial infections caused by MRSA. This is the first typing method capable of comparing the mec determinants of MRSA isolates and Mcr CNS isolates to establish the origin of the mec determinant. PMID- 7869587 TI - [Diagnosis of cytomegalovirus infection]. AB - Cytomegalovirus (CMV) is a ubiquitous pathogen and causes a variety of clinical manifestations from unapparent to fatal infections. Of these variable CMV infections, intrauterine infection and infections in immunocompromised hosts are severe and often fatal. CMV infection has been diagnosed by isolation of virus and detection of more than 4-fold increase in anti-CMV antibody titer and/or CMV specific IgM. These retrospective diagnoses, however, are not compatible to the requirement of clinical side after the appearance of anti-CMV drug, ganciclovir. The appearance of ganciclovir requires the rapid diagnosis of CMV infection which is useful for the treatment of patient. The application of monoclonal antibody and polymerase chain reaction (PCR) to CMV diagnosis made it possible to satisfy the requirement of clinical side. We developed direct immunoperoxidase method using the Fab of a monoclonal antibody against an immediate-early antigen of CMV infected cells. Using this method, CMV infection is diagnosed within 24 hours after the collection of clinical specimens. PCR is also useful for rapid diagnosis of CMV infection. In addition, PCR can detect virus DNA sequences in cerebrospinal fluid where CMV is seldom isolated even in AIDS patients with CMV encephalitis. PMID- 7869588 TI - [Problems in the diagnosis of AIDS]. AB - Diagnosis of human immunodeficiency virus (HIV) infection depends mainly on the detection of HIV-specific antibodies in the serum. If a seropositive patient has symptoms and signs of AIDS indicator diseases he (or she) will be diagnosed as having AIDS. If a patient is seronegative to HIV, some other diseases should be evaluated to explain the symptom related to the immunodeficiency. However, diagnosis of AIDS may be possible when a patient has AIDS indicator diseases and decreased CD4 positive cell count (< 400/microliters). We should also pay attention to the HIV-2 infection and idiopathic CD4 lymphocytopenia (ICL) which has been reported to be related to clinical immunodeficiency. We had a few cases with indeterminate antibody positivity. If a patient's serum is repeatedly HIV positive in a screening assay but repeatedly indeterminate in a confirmation assay, some other confirmation tests such as RIPA, PCR, p24 antigen assay, or virus isolation should be employed to demonstrate the presence of HIV-infection. PMID- 7869589 TI - [Problems concerned with adult T-cell leukemia. 1) Causes of death and early diagnosis of cytomegalovirus pneumonia in adult T-cell leukemia. 2) Clinicopathological features of CD30 positive adult T-cell leukemia]. AB - 1) We studied the causes of death confirmed by autopsy or necropsy in 23 adult T cell leukemia (ATL) patients. Of them eight showed involvement of tumor (35%), eleven infectious disease (47%) (nine cytomegalovirus (CMV) pneumonia, one varicella-zostervirus pneumonia, one pseudomonas aeruginosa pneumonia), and four others (17%). In seven recent cases treated with a new chemotherapy regimen in combination with G-CSF administration, survival was longer than in previous cases and tumor involvement as a cause of death decreased (one case, 14%). However, CMV pneumonia inclined to increase (six cases, 86%). Therefore, we tried to retrospectively detect CMV DNA in the serum of ATL patients using a nested polymerase chain reaction (PCR). CMV pneumonia was reliably diagnosed in eleven ATL patients, whereas CMV DNA was detected in all patients at the time of clinical onset of pneumonia and CMV DNA was detected only in eight patients from 7-35 days before the onset of pneumonia. These findings suggest that the nested PCR assay is a useful tool to early diagnosis CMV pneumonia in ATL patients. 2) Recently, several cases of ATL with CD30 antigen have been reported, but its clinical relevance remains unknown. Accordingly, we studied CD30 antigen expression in 36 ATL patients who had monoclonal integration of HTLV-I provirus in the tumor cells and demonstrated the immunohistochemical and clinical characteristics of these patients. CD30 antigen expression was evident in seven of these 36 patients (19.4%). A comparison of ATL cases with and without CD30 antigen expression revealed significantly large numbers of abnormal lymphocytes in the peripheral blood and lower serum calcium levels in CD30 antigen positive ATL. PMID- 7869590 TI - [Changes in serum h-HGF levels after living-related liver transplantation]. AB - It is well known that prognosis is very poor in patients with severe hepatic insufficiency such as congenital biliary atresia and fulminant hepatitis. The liver transplantation is only effective therapy for these patients and living related liver transplantation is becoming popular in Japan. We observed the changes in serum human hepatocyte growth factor (h-HGF) levels of the recipients during the operation in 3 cases of congenital atresis and one of fulminant hepatitis. Serum h-HGF values in these patients reached the maximal levels (5-10 fold compared to the base line values) at the phase of portal or hepatic artery anastomosis during the operation. These observations suggest that the increase of h-HGF in the recipient is derived from the following three origins. (1) Wash outed h-HGF from the liver of the donor. (2) Induced h-HGF from other organs than the liver of the recipient. (3) The decreased catabolism of h-HGF in recipient due to total hepatectomy. PMID- 7869591 TI - [Thyroid function in patients with anorexia nervosa and depression]. AB - Thyroid hormone levels were measured in 21 patients with anorexia nervosa, 15 patients with depression and 16 patients with severe depression and were compared with those in 53 normal subjects. In anorexia nervosa and severe depressed patients, serum T3, T4, fT3, fT4 and T3/T4 ratio showed significantly lower values than those in normal subjects. However there was no difference between depressed patients and normal subjects. The serum TSH levels were within normal range in all of the studied subjects. Thus, thyroid hormone levels in severe depressed patients were similar to those in anorexia nervosa and the changes were inversely related to disease conditions. The supplementation of thyroid hormones to antidepressant relieved clinical symptoms in some of the severe depressed patients. These results suggested that the changes in thyroid hormone levels in anorexia nervosa and severe depression were mainly due to impaired conversion of T4 to T3 by increased cortisol secretion through emotional stress. PMID- 7869592 TI - [Lp(a) serum concentrations in diabetes mellitus]. AB - Lp(a) has been considered as an independent risk factor for atherosclerosis, mainly for coronary heart disease. Recent epidemiologic studies have demonstrated elevation of Lp(a) serum concentration in diabetes mellitus. Atherosclerosis is the most common cause of death in diabetic patients, but there is little information available concerning the importance of Lp(a) in these patients. We investigated the relationship between Lp(a) serum concentration and the presence of chronic diabetic complications. Lp(a) was determined in 14 IDDM patients and 62 NIDDM patients. Median Lp(a) serum concentration in diabetics was 21.8 mg/dl, which was significantly higher than in nondiabetic controls described before. Glucose, HbA1c, fructosamine, total cholesterol, triglycerides, HDL-cholesterol, apolipoprotein A1, B and E were not associated with raised Lp(a) values. With increasing Lp(a) levels, higher prevalences of retinopathy and of albuminuria were observed. We conclude that in diabetic patients, Lp(a) levels are elevated compared with non-diabetic subjects, and that higher Lp(a) levels are associated with higher prevalences of retinopathy and of albuminuria. PMID- 7869593 TI - [Blood concentrations of thrombomodulin in patients with various diseases]. AB - Concentrations of thrombomodulin in blood plasma were measured by a one-step sandwich enzyme immunoassay (EIA). The concentrations in normal healthy subjects were 9.9 +/- 2.9 ng/ml. The concentrations were found to be significantly higher in patients with SLE, RA and other collagen diseases in their active stages than at their non-active stages. The concentrations increased in patients with DIC, and significantly higher levels were observed when DIC was complicated by multiple organ failure. These findings indicate that plasma concentrations of thrombomodulin may be a useful parameter for vascular injuries caused by inflammatory processes or coagulation/fibrinolysis reactions. PMID- 7869594 TI - [Auditory brainstem responses by click stimuli via an earphone--comparison with a headphone]. AB - To evaluate the variations of auditory brainstem responses (ABR) recorded using different receivers, the recordings of ABR were performed in 10 neurologically and audiometrically normal subjects who were all females (20-21 years of age) using a headphone (DR-513B-6) and an earphone (YE-102J). The peak latencies, the interpeak latencies, and the amplitudes of wave I, III, and V at each ABRs were compared. Unilateral auditory stimuli consisted of alternate click with 0.1 msec duration at intensity of 110 dB SPL and at rate of 13 Hz was given to the subjects who lay in the supine position at awake state. The active electrode was placed on the vertex (Cz) and the reference electrode on the left or right mastoid. The responses recorded from Cz to the ipsilateral mastoid were amplified by a factor of 10 microV/DIV with a bandpass filter of 10 Hz-3 KHz, a total of 1000 responses was averaged. It was recognized that the output intensity via the earphone was lower than the headphone, the difference was approximately 5 dB. Furthermore, the frequency response of the earphone was worse than the headphone at high frequency area (over 3.5 KHz). There were characteristic differences between ABRs recorded using the headphone and the earphone. The prolongation of the latency and the decrease of the amplitude were identified at only wave I of ABRs recorded using the earphone. However, no significant changes were founded at another components.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869595 TI - [Detection of Campylobacter species by using polymerase chain reaction and nonradioactive DNA probes. III. DNA probe for identification of C. laridis]. AB - The development of a rapid and specific DNA probe assay for identification of Campylobacter species, including C. jejuni, C. coli, C. laridis, C. fetus, and C. hyointestinalis is important in determining the precise diagnosis of Campylobacter infections. Sequence data of our previous studies for a 240-base DNA fragment was used to select primers and probes conjugated to alkaline phosphatase, complementary to a portion of DNA between primers. However, a 21 base probe (CL (1)) tested here for detection of C. laridis was cross-reactive with PCR-amplified fragments of C. jejuni, C. coli and C. hyointestinalis, although it was not reactive with C. fetus and C. fetus subsp. fetus. To solve this problem, further modifications of the probe were therefore made to improve the specificity for those particular species. A second 21-base probe with a single base-substitution (CL (2)) and a third 20-base probe (CL(3)) were ineffective for identification of C. laridis, too. A fourth 20-base probe with a single base substitution (CL(4)) was a significant improvement over the results obtained by other three probes specifically to detect C. laridis, Thus, the alkaline phosphatase-labeled probe method developed so far is an interesting alternative without access to radioisotopes for clinical laboratories for identification of Campylobacter species, including C. jejuni/coli/hyointestinalis, C. laridis, and C. fetus/fetus subsp. fetus. PMID- 7869596 TI - [Unusual transient M-proteinemia (IgG-kappa type) detected using separax membrane. A case report]. AB - We report a patients with squamous cell carcinoma of tongue showing transient M protein (IgG-kappa type) on electrophoresis using a Separax membrane. The M protein was detected in the alpha 1 to beta regions as a broad band, and it was detected in the slow gamma region as a monoclonal band on electrophoresis using other types of membranes. The unusual electrophoretic pattern of globulin found in this patient was considered to be caused by alternation of globulin by unusual sugar chains. PMID- 7869597 TI - [The 36th Congress of the Japanese Society of Nephrology. Chiba City, Japan. December 16-18, 1994. Abstracts]. PMID- 7869598 TI - Nitric oxide and the lymphatic system. PMID- 7869599 TI - Cytoplasmic free Mg2+ in rat ventricular myocytes studied with the fluorescent indicator furaptra. AB - To estimate cytoplasmic Mg2+ concentration ([Mg2+]i), ventricular myocytes enzymatically isolated from rat hearts were loaded with the fluorescent indicator, furaptra, and the fluorescence signals of single quiescent myocytes were measured at 32 degrees C. The excitation spectrum of furaptra measured in the myocytes was well-fitted by the spectra obtained in vitro; thus it was possible to calibrate the fluorescence signal in terms of [Mg2+]i. The analysis implied that about 20% of the indicator molecules were Mg(2+)-bound. Considering that the indicator likely reacts with Mg2+ with a larger KD value in cytoplasm than in vitro (by a factor of 1.2-2 as suggested for mouse and frog skeletal muscles), the [Mg2+]i for the resting single myocytes was estimated to be within 0.8-1.3 mM. Superfusion with a high extracellular Mg2+ concentration (20 mM) caused a slow and slight elevation in [Mg2+]i over a period of a few hours. Other experimental interventions, including application of a low extracellular Na+ concentration and isoproterenol, and CO2 acidosis, did not cause a detectable change in [Mg2+]i, whereas the application of an uncoupler, a blocker of oxidative phosphorylation in mitochondria, caused a rapid and large increase in [Mg2+]i. It is suggested that the [Mg2+]i is tightly maintained at around 1 mM, unless intracellular ATP is depleted. PMID- 7869600 TI - The potentiation of carbachol-induced transient contractions in guinea-pig stomach muscles by a low temperature. AB - A transient contraction in guinea-pig stomach muscles was induced by carbachol (CCh, 10(-6) M) in a Ca(2+)-free Krebs solution. This CCh-induced transient contraction (CITC) was remarkable from 22 to 26 degrees C, but not so at other temperatures in most preparations. When a second CCh (10(-6) M) was applied to the tissue with rinsing off CCh 5 min after an application of the first CCh for 10 min, no CITC was observed. The peak amplitude of the CITC increased with the CCh concentration dose-dependently, and that of CITC (by 10(-6) M CCh) declined exponentially over time after washing the tissue with a Ca(2+)-free Krebs solution. The decline time constant increased from 4.8 +/- 1.2 min (mean +/- SEM; n = 5) at 35 degrees C to 13.2 +/- 2.5 min (mean +/- SEM; n = 5) at 22 degrees C. Furthermore, the falling phase of CITC (by 10(-6) M CCh) also showed an exponential decay of 7.4 +/- 0.2 s (mean +/- SEM; n = 6) at 35 degrees C in the time constant. This time constant increased to 22.3 +/- 0.3 s (mean +/- SEM; n = 6) at 22 degrees C. From the above results, it is concluded that CITC may be due to the Ca(2+)-release from an intracellular store site while released Ca2+ may be immediately excluded to an extracellular space by the Ca2+ pump of the plasma membrane, but the Ca2+ pump activity may be reduced and in addition the stored Ca2+ is kept for long time by a low temperature, which thus results in an increase in the amplitude and a prolongation of the falling phase of CITC. PMID- 7869601 TI - Non-insulin and non-exercise related increase of glucose utilization in rats and mice. AB - The effects of high-energy phosphate contents in muscles on glucose tolerance and glucose uptake into tissues were studied in rats and mice. Enhanced glucose tolerance associated with depleted high-energy phosphates and elevated glycogen content in muscles and liver was observed in animals fed creatine analogue beta guanidinopropionic acid (beta-GPA). Distribution of infused 2-[1-14C]deoxy-D glucose in tissues especially in the soleus muscle, kidney, and brain was greater in mice fed beta-GPA than controls. The glucose uptake was decreased when the contents of ATP and glycogen were normalized following creatine supplementation. Plasma insulin in animals at rest was lower and its concentration after intraperitoneal glucose infusion tended to be less in animals fed beta-GPA than controls (p > 0.05), although the pattern of insulin response to glucose loading was similar to the control. The daily voluntary activity in beta-GPA fed mice was also less than controls. These results suggest that improved glucose tolerance is not related to elevated insulin concentration and/or decreased glycogen following exercise. Such improvement may be due to an increased mitochondrial energy metabolism caused by depletion of high-energy phosphates. PMID- 7869602 TI - Osmotic swelling activates intermediate-conductance Cl- channels in human intestinal epithelial cells. AB - During osmotic swelling of a human intestinal epithelial cell line, stepwise closing unitary events of Cl- channels could be observed in cell-attached patches upon application of large positive potentials only when inactivating whole-cell Cl- currents were simultaneously observed. The closing process became faster with increasing positive command pulses. The unitary conductance was around 32 pS at 60 mV, 37 pS at +100 mV, and 47 pS at +140 mV exhibiting outward rectification. PMID- 7869604 TI - Proceedings of the 71st annual meeting of the Physiological Society of Japan. Kagawa, March 24-26, 1994. Abstracts. PMID- 7869603 TI - A simple method for continuous measurement of cell height during a volume change in a single A6 cell. AB - A simple electrophysiological method for continuous monitoring of the height of a single renal cell in culture is described. The procedure consists of placing a patch-electrode on the apical cell surface and monitoring the current deflections during osmotic challenge. The mean increase in cell height by 78% hypotonic solution was 2.0 +/- 0.2 microns. PMID- 7869605 TI - Evidence for sympathetic, purinergic transmission in the iris dilator muscle of the rabbit. AB - Electrical transmural stimulation of isolated iris dilator muscle of the rabbit produced a transient contraction that consisted of adrenergic and nonadrenergic components. In contrast to the adrenergic component, the nonadrenergic component was resistant to prazosin and other adrenoceptor antagonists. However, both components were completely blocked by guanethidine or tetrodotoxin. Among some tested compounds including neuropeptide Y, both ATP and 2-methylthio ATP produced a transient contraction in the dilator muscle and the sustained treatment with each markedly attenuated the nonadrenergic responses to electrical stimulation and to ATP. Suramin had no effect on and alpha,beta-methylene ATP potentiated the responses to electrical stimulation and to ATP. These results suggest that the nonadrenergic contraction induced by electrical transmural stimulation is a sympathetic purinergic response that may be mediated through unique purinoceptors. PMID- 7869607 TI - Histopathological investigation on salt-loaded stroke-prone spontaneously hypertensive rats, whose biochemical parameters of renal dysfunction were ameliorated by administration of imidapril. AB - Our previous studies showed that imidapril prevented the occurrence of cerebral stroke and ameliorated biochemical parameter changes of renal dysfunction at a dose that did not inhibit the progression of hypertension in salt-loaded stroke prone spontaneously hypertensive rats (SHRSP). To confirm these findings, a histopathological investigation was conducted on the kidney of salt-loaded (from 11 to 16 weeks of age) SHRSP, which was the subject of the preceding study. Their brains and hearts were also examined. Histopathologically, renal lesions such as fibrinoid necrosis and proliferative arteritis of small calibration arteries, necrotizing glomerulitis and tubular degeneration, and cerebral hemorrhage and slight cardial hypertrophy were observed in salt-loaded control SHRSP. The occurrence of these lesions were prevented in a dose-dependent manner by the administration of imidapril (1 and 2 mg/kg/day). Especially, the preventive effects on the renal lesions were apparently noted. Enalapril also prevented these renal lesions, but its preventive effects were weaker than those of imidapril at the same dose (2 mg/kg/day). It became evident from the results of the present and previous studies that imidapril reduced renal biochemical and histopathological injuries. PMID- 7869606 TI - Involvement of beta 3-adrenoceptor in the relaxation response in guinea pig taenia caecum. AB - beta-Adrenoceptors in the guinea pig taenia caecum were investigated by measuring relaxation responses to agonists and by a radioligand binding assay using [3H]CGP 12177. The rightward shift of the isoprenaline concentration-response curve was observed by butoxamine, a beta 2-selective antagonist, and the pA2 value for butoxamine was 6.46. In control preparations, catecholamines caused relaxation with the following rank order of potency: isoprenaline > adrenaline > noradrenaline. However, in the presence of 10(-6) M phentolamine, 3 x 10(-4) M atenolol and 10(-4) M butoxamine, the rank order of potency of the agonists was: isoprenaline > noradrenaline > adrenaline. CGP 12177 caused graded relaxation of the guinea pig taenia caecum, and this response was not influenced by 10(-6) M phentolamine, 3 x 10(-4) M atenolol, 10(-4) M butoxamine or 10(-6) M propranolol. The Scatchard plot of the specific [3H]CGP 12177 binding to microsomal fractions from the guinea pig taenia caecum showed two affinity sites of the receptor: high affinity (KD = 0.64 nM) and low affinity (KD = 142.21 nM) sites. The pKD value of the high affinity site of [3H]CGP 12177 was in agreement with its pA2 value, and that of the low affinity site was in agreement with its pD2 value. These results suggest that isoprenaline-, noradrenaline- and adrenaline-induced relaxations of the guinea pig taenia caecum predominantly involve beta 2- and beta 3 adrenoceptors, whereas CGP 12177-induced relaxation is mediated solely through beta 3-adrenoceptors. PMID- 7869609 TI - Age-related changes of cholinergic markers in the rat brain. AB - To evaluate whether any degenerative changes affect the brain cholinergic systems during natural aging, we compared various cholinergic biochemical markers (number of muscarinic receptors, mAChR; choline acetyltransferase activity, ChAT; acetylcholinesterase activity, AChE; and sodium-dependent high affinity choline uptake) in the cortical (CR) and subcortical (SS) regions of the brains of aged (24 month) and young (2 month) rats. Using [3H]-quinuclidinyl benzilate ([3H] QNB) as the ligand of muscarinic receptor binding, the numbers of mAChR decreased about 30% in both the CR and the SS of aged rats compared with those in young rats, while a significant age-related increase in the affinity of mAChR was observed. [3H]-QNB binding in both the young and aged rat brain was displaced markedly by pirenzepine, while [3H]-QNB binding in the SS of the aged rat brain was displaced at low concentrations of atropine. The Vmax values of ChAT and AChE also decreased about 20-30% compared with those of young rats. The sodium dependent high affinity choline uptake was lower in the crude synaptosomal fraction prepared from aged rat brain than in young brain. Hemicholinium-3 inhibited the choline uptake in young rat brain at a concentration range of 1 microM-10 nM, but choline uptake in aged brain was insensitive to hemicholinium 3. These results indicate that natural aging brings about a diffuse and multiple depletion of various biochemical markers in cholinergic neurons. PMID- 7869608 TI - Microinjections of angiotensin II into the supraoptic and paraventricular nuclei produce potent antidiureses by vasopressin release mediated through adrenergic and angiotensin receptors. AB - We investigated the effects of angiotensin II (Ang II), microinjected into the supraoptic (SON) and paraventricular (PVN) nuclei of rats, on the urine outflow rate and underlying mechanisms. Ang II produced antidiuretic effects in a dose dependent manner with ED50 values of 0.1 and 0.05 nmol in the SON and PVN, respectively. [Sar1, Ile8]Ang II at 0.1 nmol diminished the Ang II (0.5 nmol) induced antidiureses in the SON more markedly than in the PVN. A high dose of [Sar1,Ile8]Ang II, 1 nmol, completely inhibited the effects in both the nuclei. In addition, the Ang II (1 nmol)-induced antidiuretic effects were partially inhibited by phenoxybenzamine (80 nmol) in the SON and by phenoxybenzamine, timolol (100 nmol) and propranolol (100 nmol) in the PVN. The microinjection of Ang II (1 nmol) into both the nuclei, after pretreatment with a vasopressin V1V2 antagonist, d(CH2)5-D-Tyr(Et)VAVP (i.v.) significantly increased the urine outflow rate. These findings suggest that 1) Two mechanisms account for the Ang II receptor-mediated antidiureses resulting from an increase in vasopressin release: direct stimulation on vasopressin-containing neurons and indirect stimulation on them through alpha-adrenoceptors in the SON and alpha- and beta adrenoceptors in the PVN; 2) The Ang II-induced antidiuretic effect in the SON is slightly less potent than that in the PVN; and 3) Ang II receptors in the nuclei may possibly produce the diureses through mechanisms that are not presently understood. PMID- 7869611 TI - Inhibitory action of a (1-->6)-beta-D-glucan-protein complex (F III-2-b) isolated from Agaricus blazei Murill ("himematsutake") on Meth A fibrosarcoma-bearing mice and its antitumor mechanism. AB - The effects of F III-2-b (Agaricus blazei Murill polysaccharide) with or without 5-fluorouracil (5-FU) on immune responses were investigated in Meth A tumor bearing and normal mice. The i.p. administration of F III-2-b (10 mg/kg/day x 30) moderately inhibited the growth of Meth A tumor cells implanted s.c. in mice. Development of implanted tumors was strongly inhibited by the combination of F III-2-b and 5-FU. The picryl chloride-induced delayed type hypersensitivity (PC DTH) response in mice was depressed after the implantation of tumor and treatment with 5-FU. F III-2-b restored the suppression of PC-DTH by 5-FU, but did not increase the PC-DTH of normal mice. F III-2-b not only enhanced the degree of spleen cell-mediated sheep red blood cells (SRBC) hemolysis (quantitative hemolysis of SRBC), the indexes of the spleen and thymus, and the number of spleen cells but also restored the suppressive effect of 5-FU. In the group receiving F III-2-b, the percentages of splenic Thy1.2-, L3T4- and asialo GM1 positive cells were significantly increased as compared with the tumor-bearing mice treated with saline. Furthermore, the L3T4+/Lyt2+ ratio showed a tendency to increase, and the Lyt2+ ratio was markedly decreased. These results suggest that the antitumor effect of F III-2-b may be correlated with the changing pattern of the Thy1.2-, L3T4- and asialo GM1-positive cells. PMID- 7869610 TI - Quantitative properties of plasma corticosterone elevation induced by naloxone precipitated withdrawal in morphine-dependent rats. AB - Elevation of plasma corticosterone (PCS) has been used as an indicator of morphine withdrawal, but it is not clear whether the magnitude of elevation is related to the intensity of the dependence. The dose-dependent effects of naloxone on PCS and body weight were studied in male Sprague-Dawley rats rendered physically dependent on morphine by injecting increasing doses of 40-120 mg/kg/day, s.c. twice daily for 1-6 days. Naloxone (0.01-2.0 mg/kg, s.c.) was administered 3 hr after the last morphine administration. Naloxone elevated PCS levels in a dose-dependent manner in all groups treated with morphine, and the elevation was correlated with the number of days of morphine treatment. Naloxone also reduced dose-dependently the body weight in all groups treated with morphine; in this case, a reverse correlation was obtained between the body weight changes and the PCS levels. It was confirmed that PCS elevation is a quantitative sign of naloxone-precipitated morphine withdrawal and that the elevation is indicative of the degree of morphine physical dependence. PMID- 7869612 TI - Regulation by protein kinase C of platelet-activating factor- and thapsigargin induced calcium entry in rabbit neutrophils. AB - 12-O-Tetradecanoylphorbol-13-acetate (TPA) time-dependently inhibited the platelet-activating factor (PAF)-induced rise in cytosolic free calcium concentration ([Ca2+]i) in rabbit neutrophils, whereas staurosporine significantly enhanced it. Inositol 1,4,5-trisphosphate (IP3) induced Ca2+ release in digitonin-permeabilized cells but not in PAF-pretreated permeabilized cells. IP3-induced Ca2+ release was not affected by protein kinase C activators or inhibitors. In the cells pretreated with PAF and thapsigargin in Ca(2+) deficient medium, stimulated Ca2+ entry was evoked by the subsequent addition of CaCl2. TPA inhibited the Ca2+ entry induced by PAF and thapsigargin in a staurosporine-reversible manner but not thapsigargin-induced [Ca2+]i elevation. These results suggest that protein kinase C negatively regulates PAF- and thapsigargin-induced rise in [Ca2+]i possibly by inhibiting Ca2+ store depletion induced Ca2+ entry. PMID- 7869613 TI - Morphine dependence with or without tolerance in formalin-treated mice: further evidence for the dissociation. AB - Pain associated-anxiety induced by formalin, which resulted in a significant delay in the development of tolerance to morphine antinociception, failed to prevent the development of physical dependence as evidenced by naloxone challenge. Dependence also developed in mice rendered tolerant to morphine. Thus, the development of morphine dependence was observed in the absence and presence of tolerance to morphine antinociception; Our results further confirm the dissociation of opioid tolerance and dependence in the animal model of experimental pain/anxiety. PMID- 7869615 TI - Effect of NIK-247 on basal concentrations of extracellular acetylcholine in the cerebral cortex of conscious, freely moving rats. AB - We studied the effect of orally administered NIK-247 (9-amino-2,3,5,6,7,8 hexahydro-1H-cyclopenta[b]quinoline monohydrochloride monohydrate) on basal extracellular acetylcholine (ACh) concentrations in the rat cerebral cortex using microdialysis without the addition of cholinesterase inhibitor to the perfusion fluid and radioimmunoassay for ACh. In addition, the effect of oral administration of NIK-247 on acetylcholinesterase (AChE) activity in rat cerebral cortex was determined. The mean basal ACh content in the perfusate from the cerebral cortex of freely moving rats was 123.2 +/- 21.8 fmol/30 min (n = 7). NIK 247 (2.5-10.0 mg/kg, p.o.) increased the ACh content of the perfusate in a dose dependent manner. NIK-247 at 10 mg/kg significantly increased the ACh content in the perfusate from 0.5 to 2.5 hr after administration, and the maximum increase was attained at 1 hr after administration. 9-Amino-1,2,3,4-tetrahydroacridine (5 mg/kg, p.o.) and physostigmine (0.5 mg/kg, i.p.) significantly increased the ACh content in the perfusate from 1 to 2 hr and from 0.5 to 1.5 hr after administration, respectively. AChE activities in the cerebral cortex were about 32% and 12% below the control value at 1 hr and 3 hr after administration of NIK 247 at 10 mg/kg, respectively. These findings demonstrate that NIK-247 increases extracellular ACh concentration and inhibits AChE activity in the cerebral cortex after oral administration, and they suggest that NIK-247 facilitates central cholinergic transmission. PMID- 7869614 TI - The possible role of age-related increase in the plasma glucagon/insulin ratio in the enhanced hepatic gluconeogenesis and hyperglycemia in genetically diabetic (C57BL/KsJ-db/db) mice. AB - Genetically diabetic db/db mice and their normoglycemic littermates (+/+ mice) were studied to determine plasma levels of glucose, glucagon and insulin and hepatic gluconeogenic enzyme activities. Plasma glucose levels did not differ significantly between the 5-week-old db/db and +/+ mice, but increased with age in the former until the animals were 16-week-old. Similar age-associated changes were observed in the activities of the gluconeogenic enzymes, glucose-6 phosphatase (G-6-Pase) and fructose-1,6-diphosphatase (F-1,6-DPase). While the plasma levels of insulin and glucagon that peaked at 7 weeks of age did not parallel the hyperglycemia, the plasma glucagon/insulin (G/I) ratio roughly paralleled the hyperglycemia. Analysis of individual values for the db/db mice revealed statistically significant (P < 0.001) correlations between plasma glucose levels and hepatic G-6-Pase (r = 0.78) or F-1,6-DPase (r = 0.74) activity. There were also significant correlations between the G/I ratio and plasma glucose levels (P < 0.001, r = 0.66), hepatic G-6-Pase (P < 0.01, r = 0.48) or F-1,6-DPase (P < 0.01, r = 0.57) activity. It is thus concluded that the relative predominance of glucagon over insulin action plays an important role in the age-associated development of hyperglycemia in db/db mice. Glucagon presumably activates the hepatic gluconeogenic enzymes to enhance hepatic glucose output. PMID- 7869616 TI - Mechanisms underlying stimulation of gastroduodenal HCO3- secretion by NG-nitro-L arginine methyl ester, an inhibitor of nitric oxide synthase, in rats. AB - We investigated the mechanism underlying stimulation of HCO3- secretion by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the gastroduodenal mucosa of anesthetized rats. A chambered stomach (in the presence of omeprazole) or a duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 by a pH-stat method. Intravenous administration of L-NAME increased gastroduodenal HCO3- secretion with a concomitant rise in arterial blood pressure and a decrease in heart rate, and the changes were all antagonized by simultaneous administration of L-arginine. Vagotomy had no effect on the increased blood pressure response, but significantly inhibited the decrease of heart rate and increase of HCO3- secretion caused by L-NAME. The HCO3 stimulatory action of L-NAME was also inhibited by prior administration of yohimbine or prazosin. These agents alone lowered blood pressure and reduced the magnitude of the blood pressure response caused by L-NAME, leading to inhibition of heart rate changes. When delta HCO3- output induced by L-NAME was plotted against delta blood pressure change (from basal values) under various conditions, a significant relationship was found between these two factors. These results suggest that L-NAME stimulates gastroduodenal HCO3- secretion in association with the inhibition of endogenous NO production, and this mechanism may be in part mediated by a neural reflex through the vagal efferent nerve, resulting from the pressor response to L-NAME. PMID- 7869617 TI - Utilization of an isolated, blood-perfused canine papillary muscle preparation as a model to assess efficacy and adversity of class I antiarrhythmic drugs. AB - To develop a model to predict the efficacy and adversity of class I antiarrhythmic drugs, intraventricular conduction time (IVCT), coronary blood flow (CBF), developed tension of papillary muscle (DT) and idioventricular automaticity rate (VR) were measured following drug administration in an isolated canine papillary muscle preparation cross-circulated with the heparinized blood of a donor dog. Tetrodotoxin, the prototypic fast Na+ channel blocker, and class I drugs increased IVCT and CBF, but decreased DT and VR, in a dose-dependent manner. The profiles of known class I drugs, procainamide, disopyramide, lidocaine, mexiletine and flecainide were similar, but the potencies of each drug were different. Two new class I drugs, ME3202 and AN-132, were also tested and found to have effects that were similar to that of tetrodotoxin. There was a good correlation between the doses of drugs prolonging IVCT by 50% and the canine antiarrhythmic plasma concentrations in our previous study. This model can also be used to estimate the use-dependency and the kinetics of use-dependent sodium channel block; however, it is not suitable for extensive investigation of cellular and molecular mechanisms. Thus, the use of this model facilitates the comparison of multiple cardiac effects of class I drugs and may be an effective way to better assess new antiarrhythmic drugs. PMID- 7869618 TI - Characterization of acetylcholinesterase-inhibition by itopride. AB - Itopride is a gastroprokinetic benzamide derivative. This agent inhibited both electric eel acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BuChE). The IC50 of itopride with AChE (2.04 +/- 0.27 microM) was, however, 100 fold less than that with BuChE, whereas in the case of neostigmine with AChE (11.3 +/- 3.4 nM), it was 10-fold less. The recovery of AChE activity inhibited by 10(-7) M neostigmine was partial, but that inhibited by up to 3 x 10(-5) M itopride was complete when the reaction mixture was subjected to ultrafiltration. Double reciprocal plots of the experimental data showed that both Km and Vmax were affected by itopride, suggesting that the inhibition is a "mixed" type, although primarily being an uncompetitive one. The inhibitory effect of itopride on cholinesterase (ChE) activity in guinea pig gastrointestine was much weaker than that on pure AChE. However, in the presence of a low dose of diisopropyl fluorophosphate, just enough to inhibit BuChE but not AChE, the IC50s of itopride against ChE activities were found to be about 0.5 microM. In conclusion, itopride exerts reversible and a "mixed" type of inhibition preferably against AChE. The IC50 of itopride for electric eel and guinea pig gastrointestinal AChE inhibition was 200 times and 50 times as large as that of neostigmine, respectively. PMID- 7869619 TI - Stimulatory effect of pituitary adenylate cyclase-activating polypeptide on catecholamine synthesis in cultured bovine adrenal chromaffin cells: involvements of tyrosine hydroxylase phosphorylation caused by Ca2+ influx and cAMP. AB - In cultured bovine adrenal chromaffin cells, pituitary adenylate cylase activating polypeptide (PACAP) stimulated [14C]catecholamine synthesis from [14C]tyrosine (but not from [14C]DOPA) in a concentration-dependent manner, causing maximal stimulation at 10(-7) M. The stimulatory action of PACAP was not affected by staurosporine (an inhibitor of protein kinase C) or in the cells in which protein kinase C was down-regulated by prolonged exposure to TPA (an activator of protein kinase C), whereas it was partially attenuated in Ca(2+) free medium. PACAP (10(-7) M) increased the formation of [3H]inositol phosphates, [Ca2+]i and 45Ca2+ uptake as well as cAMP. The peptide also stimulated the phosphorylation of tyrosine hydroxylase, the enzyme catalyzing the rate-limiting step in catecholamine synthesis. Catecholamine synthesis and tyrosine hydroxylase phosphorylation stimulated by the maximal effective concentration of dibutyryl cAMP or high K+, which activates Ca2+ uptake, were further enhanced by PACAP, suggesting that both cAMP- and Ca(2+)-dependent protein kinases may be involved in the stimulation of tyrosine hydroxylase phosphorylation and catecholamine synthesis caused by PACAP. PMID- 7869620 TI - Differential hypoglycemic effect of 2,5-anhydro-D-mannitol, a putative gluconeogenesis inhibitor, in genetically diabetic (db/db) and streptozotocin induced diabetic mice. AB - 2,5-Anhydro-D-mannitol (AM), a putative gluconeogenesis inhibitor, completely reversed the hyperglycemia in genetically diabetic (db/db) mice that exhibited hyperinsulinemia and enhanced hepatic gluconeogenic enzyme (glucose-6-phosphatase (G-6-Pase) and fructose-1,6-diphosphatase (F-1,6-DPase)) activities compared with the control +/+ mice. In contrast, AM only partially reversed the hyperglycemia of streptozotocin (STZ)-treated +/+ mice in which the hepatic gluconeogenic enzyme activities were enhanced to the same degree as in the db/db mice, whereas the blood insulin level was depressed. In the db/db mice, the STZ-treatment attenuated the hyperinsulinemia and exaggerated the hyperglycemia as well as the hepatic gluconeogenic enzyme activities, and it greatly reduced the hypoglycemic action of AM. Not only the dose-response curve of AM but also the time-course of the blood glucose level (expressed as % of pre-treatment value) following 320 mg/kg of AM were almost identical between +/+, STZ-treated +/+ and STZ-treated db/db mice. In the STZ-treated +/+ mice, a combination treatment of insulin (320 micrograms/kg) with AM (320 mg/kg) caused hypoglycemia that was greater than that induced by AM or insulin alone. On the other hand, in vitro studies with purified F-1,6-DPase revealed that phosphorylated AM (AM-1,6-diphosphate) but not AM itself inhibited the gluconeogenic enzyme activities. These results suggest that inhibition of gluconeogenesis is responsible, at least in part, for the hypoglycemic activity of AM. AM appears to inhibit hepatic gluconeogenic enzyme activities after being phosphorylated by an insulin-dependent mechanism. PMID- 7869621 TI - Effects of a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) on Met-enkephalin-, beta-endorphin-, dynorphin-(1-13)- and electroacupuncture-induced antinociception in rats. AB - The effects of a mixture of three peptidase inhibitors (PIs), amastatin, captopril and phosphoramidon, on methionine-enkephalin (Met-enk)-, beta-endorphin (beta-end)-, dynorphin-(1-13) (Dyn)- and electroacupuncture (EA)-induced antinociception were compared in rats. EA was performed by passing electric pulses (3 Hz, 0.1-msec duration, for 45 min) through acupuncture needles inserted into the Hoku-point. The antinociceptive effect was estimated by the hind paw pressure test. The antinociceptive effects of Met-enk and beta-end injected i.c.v. or i.t. and of Dyn injected i.t. were clearly potentiated by the PIs pretreated by the same administration routes as used for the injection of opioid peptides. The antinociceptive effects of Met-enk, beta-end and Dyn injected i.c.v. were also potentiated significantly by i.t.-PIs. PIs injected into the periaqueductal gray (PAG) potentiated EA antinociception. However, the EA effect was not affected by i.t.-PIs and was rather attenuated by i.c.v.-PIs. These results suggest that: i) Met-enk hydrolyzing enzymes are involved in the degradation of not only Met-enk but also beta-end and Dyn in the rat central nervous system; ii) Met-enk and beta-end act on both supraspinal and spinal sites, while Dyn acts only on the spinal site; iii) EA antinociception is mediated by supraspinal Met-enk and/or beta-end; and iv) an anti-opiate peptide system may be activated by EA stimulation, being susceptible to Met-enk hydrolyzing enzymes. PMID- 7869623 TI - Inhibitory effect of 4-acylaminophenol derivatives (T-0799 and T-0757), novel lipoxygenase inhibitors, on arachidonic acid-induced infiltration of polymorphonuclear leukocytes in rat skin. AB - Effects of 4-acylaminophenol derivatives, novel 5-lipoxygenase inhibitors, on the neutrophil infiltration in arachidonic acid (AA) (10 mg/site)-induced skin inflammation in rats were examined. Myeloperoxidase (MPO) activity in the skin lesion, used as an indicator of neutrophil infiltration, was significantly increased after intradermal injection of AA. Dual inhibitors of cyclooxygenase and 5-lipoxygenase, phenidone (100 mg/kg x 2, i.p. and p.o.) and BW-755C (50 mg/kg x 2, p.o.), and 5-lipoxygenase inhibitors, AA-861 (100 mg/kg x 2, i.p.) and the 4-acylaminophenol derivatives T-0799 and T-0757 (10-100 mg/kg x 2, p.o.), inhibited the increase in MPO activity 5 hr after AA-injection, but the cyclooxygenase inhibitor indomethacin (5 mg/kg, i.p.) showed no effect. These results suggest that products of lipoxygenase, but not of cyclooxygenase, are involved in the MPO activity increase (i.e., neutrophil infiltration), and that this model is useful for in vivo evaluation of 5-lipoxygenase inhibitors. It is suggested that the 4-acylaminophenol derivatives may be useful as orally active drugs for treatment of some leukotriene-mediated diseases. PMID- 7869622 TI - Induction of drug metabolizing enzymes by polychlorinated biphenyl in the parotid gland and relation to changes in vitamin A content and morphological changes. AB - The relationship between the morphological changes and vitamin A content during the development of acute toxicity induced by polychlorinated biphenyl (PCB) in mouse parotid glands was investigated. PCB was administered intraperitoneally at a single dose of 2 mg/kg. Ultrastructural studies revealed remarkable morphological changes in the rough endoplasmic reticulum, nucleus, Golgi apparatus and the secretory granules at 7 days after the administration of PCB. The activities of adenosine monophosphatase (AMPase) and alkaline phosphatase were increased 1 day after PCB administration. Then the activity of NADPH cytochrome c reductase increased 4 days after PCB administration. Subsequently, the vitamin A content of the parotid glands significantly decreased at 7 days compared with the control. These sequential changes in enzyme activities implied that the decrease of vitamin A content in the parotid glands may be partly due to catabolism of vitamin A by increased activities of microsomal enzymes induced by PCB. In conclusion, it is suggested that PCB also induces drug metabolizing enzymes in the parotid gland cells and that the acute toxicity of PCB on this tissue may occur, at least partly, through the reduction of vitamin A not only by the secondary effect from liver impairment but also by the locally accelerated catabolism of vitamin A in the mouse parotid gland. PMID- 7869624 TI - Butyrate enhances the in vitro anti-SRBC (sheep red blood cell) antibody responses in murine splenocytes. AB - Butyrate at concentrations of 200-600 microM markedly enhanced the in vitro antibody productions against sheep red blood cells (SRBC) in murine splenocytes. However, other saturated short-chain fatty acids, including acetate, propionate and valeric acid, and 4-carbon compounds such as butanol, acetoacetate and beta- and gamma-hydroxybutyrate had no such effects. The presence of butyrate in the early phase of the cell culture was crucial for enhancement of the response. Butyrate also augmented the antibody production in T-cell-depleted splenocytes supplemented with the culture supernatant of concanavalin A (Con A)-stimulated lymphocytes. Interleukin (IL)-2 secreted from splenocytes in response to SRBC was increased by adding butyrate to the culture, but IL-1 secretion was not affected. On the other hand, Con A or lipopolysaccharide-stimulated proliferation of splenocytes was partly depressed by the addition of butyrate, while Con A-induced IL-2 production was not effected. These findings suggest that butyrate may act on T and B cells to promote their differentiation during the process of antibody production. PMID- 7869625 TI - Sex differences in the anticoagulant effects of warfarin. AB - Sex differences in the anticoagulant effects of warfarin were studied in rats. Warfarin was administered to rats from 7 days of gestation until 14 weeks of age. In male rats, the normal prothrombin level in the plasma was reduced, and the blood coagulation time was prolonged by treatment with warfarin at 4, 9 and 14 weeks of age. However, in female rats, the effects of warfarin on the prothrombin level and blood coagulation time were observed at 4 weeks to the same degree as in male rats, but these effects were reduced with aging, and at 14 weeks, no effect of warfarin was observed. Rats ovariectomized at 12 weeks of age and subsequently treated with warfarin for 2 weeks showed prolongation of blood coagulation time to the same level as in warfarin-treated male rats, which was inhibited by administration of 17 beta-estradiol (100 micrograms/kg/day for 4 days, i.m.). In male rats, treatment with 17 beta-estradiol also inhibited the anticoagulant effects of warfarin without changing the warfarin level in plasma. These results suggest that there is a sex difference in the anticoagulant effects of warfarin, and that this difference may be related to the estradiol level in plasma. PMID- 7869626 TI - Evidence for the excitatory cholinergic innervation in the rabbit portal vein. AB - We examined the possible existence of excitatory cholinergic innervation in isolated rabbit portal vein. Longitudinal strips of the vein in the presence of both phenoxybenzamine, an alpha-adrenoceptor antagonist, and NG-nitro-L-arginine, an inhibitor of nitric oxide synthase, exhibited a small contraction in response to transmural electrical stimulation (ES). The contractile response to ES was augmented by physostigmine, an anticholinesterase agent, and inhibited by atropine. These findings indicate the existence of an excitatory cholinergic innervation in addition to the known adrenergic and non-adrenergic, non cholinergic innervations in the rabbit portal vein. PMID- 7869627 TI - [Completion pneumonectomy after lobectomy or bilobectomy for lung cancer]. AB - Six cases who were performed completion pneumonectomy after lobectomy or bilobectomy for lung cancer were reported. The reason for completion pneumonectomy was the recurrence of lung cancer, 4 cases; second primary lung cancer, 1 case; and the destroyed lung after bilobectomy, 1 case. The intervals between the first resection and completion pneumonectomy for the patients who were recognized the recurrence were 14, 40, 83, 112 months. This results suggest that it is important that the patients who were performed curative resection are carefully followed. The patients who were performed completion pneumonectomy had the pulmonary function as follows; more than 800 ml as FEV1. The postoperative complication were not observed for the six patients. PMID- 7869628 TI - [Reoperation for lung cancer: indications and operation methods in cardiopulmonary function]. AB - A second pulmonary resection after initial operation for lung cancer was performed 20 patients (10 with a second primary lung cancer, 8 with a metastatic lung cancer, 2 with lung abscess in pulmonary aspergillosis). All patients had radical lobectomy in first operation. Eight patients underwent completion pneumonectomy, one patient had another lobectomy, two patients underwent wedge resection after initial ipsilateral lobectomy. One patient underwent contralateral lobectomy seven patients had contralateral wedge resection after initial lobectomy. Any patient did not dead within 30 days after the reoperation, not hospital death and major complications. When a second pulmonary resection (especially, completion pneumonectomy) is required, its radicality and the need to preserve residual respiratory function and cardiac function (FEV1.0 more than 800 ml/body and %FVC more than 35%, total pulmonary vascular resistance at the unilateral pulmonary artery artery occlusion test less than 700 dyne.sec.cm-5/m2) must be considered in making the decision to operation. The five-year survival rate after reoperation for patients with lung cancer was 41.0% according to the Kaplan-Meier methods. Patients with a second primary lung cancer (the three-year survival rate, 83.5%) have appeared to do better than those with pulmonary metastasis from lung cancer (the five-year survival rate, 25.6%) These results suggest that reoperation for lung cancer can be done safety, patients undergoing reoperation have a reasonable prospect for long-term survival. PMID- 7869629 TI - [Reoperation for recurrent or second primary lung cancer]. AB - From 1975 to July 1994, twenty patients underwent second or third pulmonary resections for 7 recurrent lung cancers and 14 second primary lung cancers. The initial surgical procedures were lobectomy in 18, pneumonectomy in 1 and bilateral segmentectomy in 1. The procedures at the second operation were completion pneumonectomy in 4, ipsilateral wedge resection in 3, contralateral lobectomy in 1, contralateral segmentectomy in 4, contralateral wedge resection in 7 and resection of left main bronchus in 1. At the third operation, wedge resection was done in one 28 months after completion pneumonectomy. There was no operative death following second and third operations. Five-year survival rate following second operation in 20 patients was 32.3%, and it was 28.6% for patients with recurrent lung cancers, and 31.2% for multiple primary lung cancers. In conclusion, an aggressive surgical approach for reappearing lung tumor should be performed. At the reoperation, wedge resection for recurrent lung cancers, completion pneumonectomy for ipsilateral primary lung cancers and segmentectomy for contralateral primary lung cancers should be chosen for the standard surgical procedure. PMID- 7869630 TI - [The result of reoperation for lung cancer]. AB - Twenty four patients with recurrent or multiple lung cancer were reoperated in our center. Five-year survival rate was 20% for 11 patients with recurrent, while was 25% for 13 patients with multiple after reoperation. The patients with limited operation had well survival and there was no significant difference in procedure. However all four patients with N2 had poor prognosis. Seven patients (29%) had the post reoperative complication in pulmonary system. All of them had the impairment of pulmonary function (FEV1.0% was less than 50%) or more than 75% perfusion ratio, measured with pulmonary perfusion scintigraphy, in the side of the reoperation. PMID- 7869631 TI - [Clinicopathological study on reported case for bronchogenic carcinoma]. AB - After a primary operation for bronchogenic carcinoma, eight out of 253 patients (3.2%) underwent reoperation for local recurrence or intrathoracic metastasis. The histology was well or moderately differentiated adenocarcinoma in all cases. The average interval between the first and second operation was 34 months (range: six to 63 months). There were three local recurrences, two lung metastases and one mediastinal lymph node metastasis (#3a) ipsilaterally two lung metastases contralaterally. Completion pneumonectomy was underwent in one, wedge or segmental resection in five and excision of lymph node in one case after an initial ipsilateral lobectomy. Two patients underwent contralateral wedge or segmental resection after initial lobectomy. Four of eight patients died of brain, liver, or bone metastases after reoperation, the time of survival averaging 63 months. Two patients died of pneumonia, the time survival averaging 92 months. Two patients are still alive, one in 52 months and another in 20 months after reoperation. PMID- 7869632 TI - [Reoperation for recurrent and second primary lung cancer]. AB - Thirty patients have undergone multiple resections for non-small cell lung cancer from 1973 to July 1994, constituting 2.6% of 1,153 who had undergone pulmonary resection for such tumor. In the 22 patients for recurrent cancer, 15 resections of the ipsilateral lung and 9 of the contralateral lung were performed with no operative death. The survival rate following second resection in 22 patients was 33.8% at 3 years and 13.5% at 5 years. Survival rate was poor in patients with DNA aneuploid primary tumor and there was not a patients of 5 years survival. Three out of the 5 patients which had a diploid pattern in the primary tumor, showed an aneuploid pattern in the recurrent tumor. Long survival patients were founded only in the patients which had a diploid primary tumor. In the 8 patients for second primary lung cancer, 4 resections of the ipsilateral lung and 4 of the contralateral lung were performed, including two bronchoplastic surgery for early hilar squamous cell carcinoma. The survival rate following second resection in 8 patients was 64.2% at 5 years with good result. We concluded that an aggressive surgical approach is safe and warranted in patients with second primary lung cancer. PMID- 7869633 TI - [Completion pneumonectomy for local recurrence of lung cancer]. AB - Completion pneumonectomy refers to an operation intended to remove what is left of a lung partially resected during a previous operation. The procedure is seldom indicated and the risk of operative mortality and morbidity is higher than standard pneumonectomy. Four patients underwent completion pneumonectomy for recurrence of lung cancer. The first patient had metastatic lesion of hilar lymph nodes more than five years after surgery. The second one had received preoperative radiation therapy and the third had very poor pulmonary function. The last one had underwent pulmonary resections twice during twelve years. Each case was relatively uncommon and gave the difficult surgical problem, but all patients survived the operation and are doing well at present. PMID- 7869634 TI - [Resection of recurrent lung cancer]. AB - The resected recurrent lung cancer cases were evaluated retrospectively. Out of 1,060 cases who received an operation due to primary lung cancer, 21 (1.8%) had recurrent lung cancer which were resected subsequently. Stage I adenocarcinoma cases were found to be most frequent at the first operation (76%). Out of 21 cases, 7 received completion pneumonectomy, 5 had lobectomy and 8 had limited operation, respectively. The 5-year survival rate after the second operation was 36.6% in all the cases. There was no statistical difference in survival rate between the lobectomy group (including completion pneumonectomy) and the limited operation group. There was statistical difference in survival rate between cases who received a second operation in a time span of 2 or more years after the first operation and the cases who received it in less than 2 years. Good prognosis can be expected after the resection of recurrent lung cancer, but further analysis would be required in evaluation of respiratory function as well as biological malignancy of the tumor. PMID- 7869635 TI - [Results of surgical treatment of intrathoracic recurrence after complete resection of non-small cell lung cancer: clinical significance of subsequent lesion in lung parenchyma]. AB - Results of surgical treatment for 33 intrathoracic recurrence after complete resection of non-small cell lung cancer were analyzed. Prognosis of the second surgical treatment were favorable in patients with subsequent cancer with in situ component and solitary lesion in lung parenchyma. Retrospective study of 53 patients who recurred and were thoroughly followed up their clinical course until lung cancer death revealed that the solitary one tends to be confined to the intrathoracic location, and the multiple one did not confined to the intrathoracic location but also extended to the extrathoracic distant metastasis or to the supraclavicular lymph nodes. PMID- 7869636 TI - [Pulmonary thromboembolism]. PMID- 7869637 TI - [Changes in intraoperative and postoperative colloid oncotic pressure after open heart surgery especially in relation to non-blood priming or blood priming]. AB - In order to evaluate the colloid oncotic pressure (COP) is useful index of hemodynamics and respiratory recovery after open heart surgery, cardiac index (CI), pulmonary capillary wedge pressure (PCWP), (A-a) Do2 and COP were measured in 34 patients during 48 hours after the cardiopulmonary bypass (CPB). The patients were divided into non-blood priming group: 11 patients and blood priming group (23 patients). In addition, blood priming group divided into two groups, one with dopamine (more than 15 micrograms/kg/min), epinephrine or intraaortic balloon pumping (severe blood subgroup, n = 6) and the other without these treatments after open heart surgery (slight blood subgroup n = 17). The COP levels in the non-blood priming group were significantly higher than those in the blood priming group from aortic cross-clamp to 10 minutes after aortic declamping (p < 0.01). From 1 to 48 hours after CPB, COP in the non-blood priming group and slight blood subgroups was significantly higher than severe blood subgroups (p < 0.05). CI and COP-PCWP levels were significantly higher in the non-blood priming group and slight blood subgroups than those in the severe blood group (p < 0.05). It is concluded that COP is useful index of hemodynamics and respiratory recovery after open heart surgery and our priming system without blood is effective in order to eliminate the blood transfusion. PMID- 7869639 TI - [Post operative mediastinitis: the experience of two cases after graft replacement of the ascending aorta]. AB - A mediastinitis after a graft replacement of the ascending aorta is serious complication and sometimes could be lethal. We have experienced two cases of such a condition, recently. In both cases, the debridement of the mediastinum and omental transposition were performed. Case 1 had a recurrent mediastinitis due to residual dead space infection, but was cured by a percutaneous drainage and a continuous irrigation. In case 2, the omentum was carefully positioned to occupy the dead space around the graft, because of the experience of the first case and gave a good result. We believe that omental transposition is an effective treatment for the postoperative mediastinitis. PMID- 7869638 TI - [Surgical treatment of infective endocarditis: application of DNA probe method]. AB - DNA probe method is a new bacteriological method for diagnosis of bacteria. The authors tried to apply the method to diagnosis of bacteremia and treatment of infective endocarditis. We could diagnose the patient's illness as bacteremia with this method even when blood cultures are not positive. We suggest that cardiac surgery should be performed in case bacteria is detected repeatedly with DNA probe method. Therefore it is useful for decision whether cardiac surgery for patients with active infective endocarditis should be done or not. PMID- 7869640 TI - [A case of successful surgical treatment of recrudescent stanford type A aortic dissection after early thrombogenic closure and reduction of dissecting lumen]. AB - A 51-year-old woman was admitted with acute chest and back pain. A CT scan (2 hours after onset) was demonstrated acute type A aortic dissection. The dissecting lumen was already closed with thrombus. A DSA was performed. It showed no intimal tear and a normal aortic figure. Repeat CT (5 hours after onset) was performed. It showed reduction of dissecting lumen compared with previous CT. Although medical treatment was continued, she recomplained intermittent slight chest and back pain. On the sixteenth day after her admission, repeat CT revealed recrudescent dissection and opened dissecting lumen of ascending aorta. Graft replacement was successfully performed using circulatory arrest and retrograde cerebral perfusion. She was discharged in good health. PMID- 7869641 TI - [Surgical therapy for local recurrence and distant metastasis of lung cancer]. AB - Twenty-two patients underwent surgical therapy for local recurrence and distant metastasis of lung cancer. Twenty patients were resected the tumor and 2 patients received the operation to improve their quality of life. Seven patients were resected lung metastasis, which were 5 adenocarcinomas and 2 squamous cell carcinomas. All metastasis situated in contralateral lung of primary operation. Two lobectomies, 1 segmentectomy, and 4 partial resections were performed. The 5 year survival rate was 28.6%. Four patients were resected brain metastasis, which were 2 adeno-squamous cell carcinomas, 1 squamous cell carcinoma, and 1 large cell carcinoma. The 5-year survival rate was 25%. Three patients were resected the neck and upper mediastinal lymph node metastasis. Since those lymph nodes could not be dissected at the initial operation, different approaches, which was median sternotomy and collar incision of neck, were selected. Two patients were alive 5 months after operation. There were no long-term survivors in 5 patients with bone or soft tissue metastasis. Since the differentiation of lung metastasis from the second primary tumor is impossible, the single lung metastasis should be resected. Resection of single brain metastasis provides better prognosis. PMID- 7869642 TI - [A case of mitral regurgitation due to partial papillary muscle rupture whose etiology was unknown]. AB - The etiology of the papillary muscle rupture includes myocardial infarction, trauma, hypertension, myxomatous degeneration, endocarditis etc. We report a case of partial papillary muscle rupture whose etiology was unknown, in a 77-year-old woman. The preoperative catheterization and coronary angiography showed severe mitral regurgitation and no significant coronary stenosis. And we recognized the mass waving into the left atrium in systole with the echocardiogram. At surgery, we repaired the mitral valve by resecting quadrangular areas of the posterior leaflet including the attachment of the torn papillary muscle. Additionally a number 28 Carpentier-Edwards mitral annuloplasty ring was sewn in place. In pathologic specimen, there were focal fibrosis, necrotic muscle, lymphocytes, and no vegetation. PMID- 7869643 TI - [Current status of extracorporeal shock wave lithotripsy in the treatment of urolithiasis]. AB - Extracorporeal shock wave lithotripsy became a main treatment method for the upper urinary tract calculi. About 500 ESWL machines of 28 types are currently used in Japan and ESWL therapy occupies more than 90% of the surgical intervention for upper tract stones. The doctors who are engaging in the ESWL therapy are strongly advised to know the features of their own ESWL machines, since the treatment strategy may differ considerably depending on the type of machines. The strategy has changed from the in-patient ESWL under anesthesia by original Dornier HM-3 to out-patient anesthesia-free treatment by machines of second or third generations. At present, it is reasonable to treat the easy stones by initial out-patient ESWL without anesthesia. When the initial ESWL fails, the second ESWL may be performed under anesthesia with the help of various auxiliary procedures. If one use the machines requiring anesthesia, one should employ every possible ancillary procedures, e.g. ureteral catheterization, stenting, push-up etc. at the time of first session to achieve the highest pulverization rate and the highest stone free rate. The treatment strategy should be assessed individually in every case of problem stone. Simple repetition of ESWL at out-patient clinic should be avoided in these cases. In the case of staghorn calculi, especially of a large stone burden with calyceal dilatation, ESWL is not advised to be an initial treatment. In the review article, the author surveyed recent clinical reports on ESWL therapy and tried to convey their treatment strategies. The article may hopefully helps the readers to establish their own policy in the ESWL treatment for urolithiasis. PMID- 7869645 TI - [Theoretical analysis about an optimal screening interval for renal cell carcinoma]. AB - In recent years the number of incidentally detected renal cell carcinoma (RCC) has increased. It is undoubtedly true that ultrasonography is the most useful tool to detect RCC in small size. However, the optimal interval of ultrasound examination is unknown. To elucidate this, we investigated the growth rate of RCC during the period of non-treatment in 6 patients. Their growth was slow and the tumor volume doubling time ranged 372 to 579 (468 +/- 84.6) days. Based on this growth rate, we conclude that we can detect the majority of RCC ranging from 1.5 to 3 cm in diameter if ultrasonography is repeated every 3 years and that the age of subjects for screening is over 40 years. PMID- 7869644 TI - [Clinical study on female patients with bladder irritability--comparison between cystitis and urethral syndrome]. AB - We analysed the clinical background of female who had no underlying disease but consulted out urology outpatient clinic with a chief complaint of symptoms of bladder irritation. Overally, 50.1% (102/200 cases) of the cases had urethral syndrome, without pyria or bacteriuria. Plotting of the age distribution of the urethral syndrome cases showed a bell-shaped curve, with the peak at the 40-49 year-old age bracket. The age distribution for the cystitis cases showed two peaks: at 20-29 years of age and 60-69 years of age. These results indicate that the cases of urethral syndrome involve multiple factors with increasing age. Examination of the external genitalia revealed the urethral smear specimens to be positive for leukocytes in 48.9% (88/180 cases) of the total urethral syndrome cases and in 72.7% (16/22 cases) of the urethral syndrome cases positive for urethral bacteria. Accordingly, it was surmised that there is considered to be a precursor of cystitis-as a cause of urethral syndrome cases. In addition, the rates of detection of chlamydia trachomatis from the vagina and urethra of the urethral syndrome cases in the reproductive age range of (2/34 cases) for the urethra. However, these rates were about the same as those determined for healthy volunteers. Nevertheless, it was surmised that urethritis or vaginitis caused by C. trachomatis was one of the causes of the symptoms of bladder irritation in some of the cases. Accordingly, it was concluded that infection due to C. trachomatis cannot be ignored as a possible cause of urethral syndrome. PMID- 7869646 TI - [Laparoscopic pelvic lymphadenectomy in prostate cancer]. AB - We described the clinical results and efficacy of laparoscopic pelvic lymphadenectomy for localized prostate cancer. This procedure was followed by radical prostatectomy, if metastasis was not found in frozen section. In the presence of positive nodes, optional treatment, such as TUR or castration, other than radical prostatectomy was performed. We performed laparoscopic lymphadenectomy on twenty seven patients between April 1992 and September 1993. They range from 52 to 78 years in age and consist of 4 patients with stage A2, 17 with stage B, and 6 with stage C. We dissected the obturator lymph nodes on bilateral sides. The average operating time was 162 minutes (range 86 to 320 minutes). The average number of nodes removed from the right side was 7.1 +/- 5.9 and 6.1 +/- 4.5 from the left side, which was comparable to the number of lymph nodes obtained by open dissection. Colon injury occurred in one patient, which was managed by laparotomy procedure. Nodal metastases were found in 6 patients by frozen section, and in 10 patients by permanent section. This discrepancy suggested that two-staged operation might be preferable for the localized prostate cancer. Six patients were given suitable therapies besides radical prostatectomy. Laparoscopic pelvic lymphadenectomy is a safe and useful procedure for prostate cancer, especially for the patients who are likely to have nodal metastasis. PMID- 7869647 TI - [An epidemiological study of urogenital cancer in Gunma Prefecture]. AB - The incidence and mortality rate of urogenital cancers in Japan are both low compared to those in western countries. However, the incidence and mortality patterns of cancer in Japan are currently becoming closer to those of western countries, and the importance of urogenital cancers is increasing. We conducted an analysis of urogenital cancers in Gunma Prefecture. The subjects were newly detected urogenital cancer patients living in Gunma Prefecture diagnosed between 1985 and 1992. Details were as follows: prostate cancer 1411, bladder cancer 1253 (male 937, female 316), renal cell carcinoma 411 (male 287, female 124), renal pelvic and ureter cancer 187 (male 127, female 60) and testicular cancer 162. Incidence rate was calculated by year, district and age, and was expressed per 100,000/year and was adjusted to world population. Regarding the incidence rate per year for males, that of prostate cancer and renal cell carcinoma increased dramatically from 8.3 to 13.6 and from 1.1 to 3.2, respectively. Incidence rate of other cancers in males showed a slight increase or remained almost stable. Incidence rate by year for females showed a slight increase or remained almost stable as a whole. Gunma Prefecture was divided into 10 districts by the range of daily life of people and the incidence rates of prostate cancer, bladder cancer and renal cell carcinoma for each district were calculated. Incidence rate of prostate cancer tended to be higher in the northern parts of the prefecture, while that of bladder cancer showed no detectable trend.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869649 TI - [Roles of sacral spinal alpha-adrenoceptive mechanism in micturition reflex in the decerebrate dog]. AB - Roles of sacral spinal alpha-adrenoceptive mechanism in micturition reflex were examined in 19 decerebrate dogs. Alpha 1- and alpha 2-adrenergic agents were injected into the sacral subarachnoidal space. Micturition reflex was evoked by filling the bladder before and after the drug injection. The intravesical pressure (IVP), the intraurethral pressure (IUP) and the electromyogram (EMG) of the external urethral sphincter muscle (EUS) were recorded simultaneously. The bladder volume, the IVP at the threshold of micturition reflex, the minimum IUP, the maximum IUP and the mean IUP were measured during collecting phase. The maximum IVP and the minimum IUP were measured during contraction phase. The effects of adrenergic agents on these measured parameters were analyzed using Wilcoxon's test. The changes of the EUS-EMG were also studied. Intrathecal injection of phenylephrine, an alpha 1-agonist, significantly increased the bladder volume and the mean IUP during the collecting phase, and tended to enhance the EUS-EMG during both phases. Intrathecal injection of prazosin, an alpha 1-antagonist, tended to diminish the EUS-EMG during both phases. Intrathecal injection of clonidine, an alpha 2-agonist, significantly decreased the minimum IUP, the maximum IUP and the mean IUP during the collecting phase, and tended to diminish the EUS-EMG during both phases. Intrathecal injection of yohimbine, an alpha 2-antagonist, decreased the maximum IVP during the collecting phase significantly. These results suggest that the sacral alpha-adrenoceptive mechanism mediates elevation of the threshold of micturition reflex and facilitation of the EUS activity via alpha 1-receptor, while facilitation of the bladder contractility and inhibition of the EUS activity via alpha 2-receptor. PMID- 7869648 TI - [Voiding dysfunction after abdominal radical hysterectomy. Comparison between patients with and without adjuvant irradiation therapy]. AB - We evaluated 59 patients with voiding dysfunction after abdominal radical hysterectomy for uterine cancer. Of 59 patients, 45 underwent the surgery alone, and the other 14 underwent surgery and postoperative radiotherapy. Irradiation (mean dose, 60 Gy) was performed in bilateral commoni iliac regions excluding the bladder. In principle, the indwelling urethral catheter was removed 4 days after operation. All patients were followed up at the gynecological department until the onset of the voiding dysfunction. The mean interval between operation and the onset of voiding dysfunction was significantly longer (P < 0.01) in the group treated by surgery alone (7.9 years) than in the group treated by surgery in combination with radiotherapy (3.8 years). Voiding dysfunction developed earlier as the age at the time of operation was higher. No differences were observed in the volume of residual urine, the detrusor function, or the incidence of urinary tract infection between the two groups. These results suggest that aged patients develop voiding dysfunction earlier after radical hysterectomy than young patients, and postoperative radiotherapy shortens the interval between operation and the onset of postoperative voiding dysfunction. PMID- 7869650 TI - [Anesthesia-free extracorporeal piezoelectric shock wave lithotripsy for urolithiasis]. AB - In November 1991, a third generation extracorporeal shock wave lithotriptor (Piezolith 2500) was installed in our clinic. We examined the effective and safe aspect of this machine for urolithiasis. From November 1991 to October 1993, we experienced 530 sessions of ESWL treatment on 235 patients (270 cases). All patients except two underwent ESWL treatment without anesthesia, and in situ ESWL treatment was possible on 247 cases. The mean number of shock waves and sessions per patient of renal stone were 3369 and 2.1, respectively. Those of ureteral stone were 3970 and 1.9, respectively. The complete removal rate of renal and ureteral stone 3 months after the last session were 86% and 92%, respectively. This outcome was very satisfactory. On the other hand, endoscopic procedure was needed on 13 patients. In almost all cases hematuria was noted after ESWL, but major complications such as subcapsular hematoma or gastrointestinal hemorrhage were not experienced at all. It was concluded that Piezolith 2500 was very effective and safe in the treatment of urolithiasis. PMID- 7869651 TI - [Chronological changes in autoantigenicity of autologous testicular germ cells in C3H/He mice during the postnatal period]. AB - Our recent studies demonstrated that experimental autoimmune orchitis (EAO) model was produced in C3H/He mice with high incidence by two subcutaneous injections of viable syngeneic testicular germ cells (TC) without the use of any adjuvants or immunopotentiators. In this study the developmental patterns of autoantigenicity of TC during postnatal period were investigated by examining the orchitogenic activity of TC, the lymphostimulatory activities of TC (including the TC-induced in vitro lymphocyte proliferative response and the cytokine release from sensitized spleen cells (SPC) in response to TC) and the immunohistochemical localization of target autoantigens in the testes of mice at various weeks of age. Delayed-type hypersensitivity-inducing capacity and anti-TC antibody eliciting capacity were initially observed in mice that were immunized with TC of 4-week old (w.o.) mice. The TC from 6-w.o. mice had the capability of inducing EAO (orchitogenicity) for the first time. A significant stimulation of in vitro lymphocyte proliferative response, as well as of interleukin (IL) 5 and IL-6 production by sensitized SPC were detectable when TC of mice 3-w.o. or more than were employed as stimulant. IL-2 and interferon gamma production were detected with TC of 4-w.o. mice. Immunohistochemical staining reaction with anti-TC antisera was primarily localized at the acrosomal portion of spermatids and spermatozoa in the seminiferous tubules, being already detected in spermatids of as early as 3-w.o. mice. Thus, from these data it is suggested that the appearance of the lymphostimulatory activities of TC consistently precedes that of the orchitogenic activity and that relatively mature germ cells such as spermatids and spermatozoa developing in the testes during the postnatal weeks may be responsible for the induction of disease and relevant immune responses in our EAO system. PMID- 7869652 TI - [A case of multilocular cystic renal cell carcinoma treated by partial nephrectomy associated with adrenal tumor]. AB - A case of multilocular cystic renal cell carcinoma was reported. The patient was 69-year-old male who had been examined for postoperative study of gastric cancer by abdominal CT. The abdominal CT incidentally revealed right adrenal tumor which was non-functional and multilocular cysts in the lower pole of the right kidney. Selective renal arteriography showed a hypovascular mass with fine neovascularity. These two findings of CT and arteriography were though to represent a probable malignant tumor but renal function of the patient decreased moderately. Surgical exploration was done and right renal masses were thought to be seen benign multilocular cysts without capsule. Simple excision of the wall of cysts and right adrenalectomy were performed. Pathological examinations showed multilocular cystic renal cell carcinoma and benign adrenal hyperplasia. Additionally partial nephrectomy was done. Surgical margin of the kidney was tumor free and postoperative course was uneventful. Prognosis of multiocular cystic renal cell carcinoma is good, therefore conservative surgery is recommended. PMID- 7869653 TI - [Prolonged exposure to intravesical foreign body induces a giant calculus with attendant renal dysfunction]. AB - A 31-year-old man came to our hospital complaining of severe voiding pain. He had inserted a fishing line made of nylon into his urethra at the age of eighteen, which was unable to be taken out and had been left there for 13 years. Preoperative ultrasonogram showed severe bilateral hydronephrosis and the serum BUN and creatinine level were as high as 45.2 mg/dl and 4.8 mg/dl, respectively. A huge bladder stone was demonstrated in X-ray film, the patient was admitted and vesicolithotomy was performed. The size of the stone was 10.5 x 7.5 x 7.5 cm and the weight was 360 grams. The fishing line was found inside the stone and the length was over 3 meters. The serum BUN and creatinine level after the operation were still high as 28.4 mg/dl and 4.1 mg/dl, respectively, and they did not improve even after six months following. PMID- 7869654 TI - [A case of 48 XXYY Klinefelter's syndrome]. AB - We observed a patient with 48 XXYY Klinefelter syndrome who visited our hospital because of a short penis as chief complaint. The patient was a 21-year-old, tall and obese man. He had gynecomastia. The penis was short and bilateral testes were underdeveloped. Endocrinologically the LH and FSH showed high level and the testosterone was low. A diagnosis of very rare 48 XXYY Klinefelter was made based of the chromosomal analysis. PMID- 7869655 TI - New Markers of Renal Diseases. Proceedings of a meeting. Telfs, Tyrol, Austria, October 6-8, 1993. PMID- 7869656 TI - Tubulopathy with macroalbuminuria due to diabetic nephropathy and primary glomerulonephritis. AB - Tubular damage is a recognized feature of both overt diabetic nephropathy and glomerulonephritis. However, the pattern and mechanism of tubular damage in the two clinical settings remain unclear. Two groups of patients with macroalbuminuria (albuminuria > 300 mg/day) were studied. Group 1 comprised 41 patients with biopsy proven primary glomerulonephritis and group 2 comprised 28 patients with clinical diabetic nephropathy due to insulin dependent diabetes mellitus. Serum creatinine, creatinine clearance, glomerular proteinuria (albuminuria and transferrinuria), markers of tubular damage such as urinary excretion of lysosomal enzyme (N-acetyl glucosaminidase), brush border enzymes (leucine aminopeptidase and gamma-glutamyl transferase) and retinol binding protein (tubular protein) were measured. Both groups were comparable in serum creatinine, creatinine clearance, glomerular proteinuria and excretion of N acetyl-glucosaminidase. However, a significantly higher degree of tubular brush border enzymuria and a lower level of tubular proteinuria were seen in group 1 than in group 2. In group 1, albuminuria correlated to tubular enzymuria and tubular proteinuria. However, there was no correlation in diabetic patients between parameters of glomerular and tubular damage or dysfunction. The data presented suggested that the pattern of tubulopathy is different in patients with comparable degree of macroalbuminuria due to diabetic nephropathy and glomerulonephritis. Moreover, in diabetic nephropathy contrary to glomerulonephritis, markers of tubular damage are unrelated to glomerular proteinuria. This may suggest different mechanisms of tubular damage in the two clinical settings. We recommended that in all patients with proteinuria, particularly those with diabetic nephropathy, markers of renal tubular damage may be useful in monitoring the course of their disease. PMID- 7869657 TI - Retinopathy in type II diabetes mellitus associated with above-normal urinary excretion of RBP. AB - We performed a cross-sectional study on the urinary excretion profiles of albumin (a marker of glomerular dysfunction) and retinol-binding protein (a low molecular mass protein marker of renal proximal tubular dysfunction) in non-insulin dependent (Type II) diabetics, with or without retinopathy. The urinary excretion of both proteins, in particular retinol-binding protein, was significantly higher in patients with background/proliferative retinopathy compared to patients without retinopathy. The degree of retinopathy correlated to the urinary excretion of albumin (P < 0.005) and retinol-binding protein (P < 0.0001). Retinopathy occurred at a higher frequency in patients with above-normal urinary excretion of retinol-binding protein, both in the absence or presence of micro/macroalbuminuria. The frequency of retinopathy among micro/macroalbuminuric patients with a normal urinary excretion of retinol-binding protein did not differ significantly from that observed in patients with a normal urinary excretion of both proteins. We cannot explain the association between retinopathy and proximal tubular dysfunction in Type II diabetes. However, it is possible that both phenomena are related to a common pathogenetic factor. PMID- 7869658 TI - Diagnostic strategy to monitor diabetic nephropathy. AB - Although much evidence supports the theory that microalbuminuria is predictive of the development of clinical diabetic nephropathy, other experimental data fail to support this conclusion. It remains unclear whether random urine samples offer as much clinical information as timed overnight or 24 hour samples. Clinical decisions as to treatment based on improved glycemic control or enhanced antihypertensive treatment should be structured to the urinary albumin concentration. Tubular dysfunction is common in diabetes, but is clinical relevance remains unclear. PMID- 7869659 TI - Analysis of mononuclear cells in urine using flow cytometry in glomerular diseases. AB - Analysis of urinary substances, such as low molecular weight proteins and enzymes localized in the proximal tubulus and cytokines, has been proposed as being useful in monitoring the disease activity of glomerulonephritis [1-4]. However, most of these markers are more closely associated with renal tubulointerstitial injury than glomerular injury. It has been demonstrated that mononuclear cells (macrophages and lymphocytes) are involved in the pathogenesis of various types of human glomerulonephritis, as well as in animal models [5-7]. If mononuclear cells are involved in glomerular injury, it can be assumed that such cells could be detected in urine; however, to our knowledge, the characterization of mononuclear cells in urine has not been investigated. We have recently demonstrated that increased numbers of mononuclear cells are observed in the urine of patients with active IgA nephropathy and that the extent of active crescents in biopsy specimens is significantly correlated with the number of urinary macrophages and natural killer cells [8]. The aim of the present study is to evaluate the clinical usefulness of analyzing mononuclear cells in urine as a non-invasive diagnostic tool for glomerular injury. PMID- 7869660 TI - Mechanisms of glomerular proteinuria and hematuria. AB - The barrier function of glomerular capillaries in vivo, which prevents the leakage of plasma proteins and cellular elements, depends not only on the basic morphological and physico-chemical fine structure of the glomerular capillary wall, but also on a functional barrier maintained by components obtained from blood. Together, both restrict the leakage of plasma proteins and cells in vivo. Two types of morphological defects are claimed to represent the normal condition: a larger type of leak, which enables the passage of red cells through the glomerular capillary wall one after the other without interruption by a plasma pulse and which must be present more frequently in thin basement membrane disease. This type of leak is sealed by penetrating cells and uncovered for protein filtration in the isolated (cell-free) perfused rat kidney. A smaller type of leak cannot be sealed by red cells, but also contributes to the enhanced protein permeability in perfusion with a monocomponent albumin solution. This type of leak is uncovered in vivo by angiotensin or catecholamines and is the basic route responsible for the unselective "functional proteinuria" of different types. Mechanisms which induce lesions under pathological conditions may also be active under everyday conditions, although to a smaller extent. PMID- 7869661 TI - Proton nuclear magnetic resonance urinalysis: coming of age. PMID- 7869662 TI - Virulence determinants of uropathogenic Escherichia coli and Proteus mirabilis. AB - The urinary tract is among the most common sites of bacterial infection and E. coli is by far the most common infecting agent. In patients with urinary catheters in place or structural abnormalities of the urinary tract, Proteus mirabilis is also a frequent isolate. To study virulence of these bacterial species, we have isolated the genes that encode putative virulence factors, constructed specific mutations within these genes, introduced the mutation back into the wild type strain by allelic exchange, and analyzed these mutants for virulence in appropriate in vitro and in vivo models. Specific virulence markers have been identified for strains that cause urinary tract infection. For E. coli, these include P fimbriae, S fimbriae, hemolysin, aerobactin, serum resistance, and a small group of O-serotypes. Redundant virulence factors must be present in these organisms as mutation of the most clearly identified epidemiological marker, P fimbriae, does not result in attenuation of a virulent strain. For P. mirabilis, urease appears to contribute most significantly to virulence. Fimbriae play a significant but more subtle role in colonization. Hemolysin, although potently cytotoxic to renal cells in vitro, does not appear to contribute significantly to the pathogenesis of ascending urinary tract infection. We can conclude that the pathogenesis of urinary tract infection and acute pyelonephritis caused by uropathogenic E. coli and P. mirabilis are multifactorial, as mutation of single genes rarely causes significant attenuation of virulence. PMID- 7869663 TI - Strategies and criteria for developing new urinalysis tests. AB - Urinalysis provides a non-invasive means to sequentially evaluate renal function and disease processes. Contemporary analytical techniques and the rapidly expanding knowledge of cell biology are yielding new ways of looking at urine constituents. Application of these new analytical techniques to screening, diagnosing and monitoring renal disease requires much more information than is currently available about the correlation of urine analytes with disease processes. Case definitions for specific renal disease depend upon a knowledge of natural history, response to therapy and laboratory data, including biopsy. When tests are being used to detect early stages of renal damage the subjects must be followed for months or years before a definitive diagnosis of irreversible disease can be established; therefore, prospective studies must be used to validate these tests. Analytes chosen for further study should be linked to significant renal pathophysiological processes. Gold standards for evaluating the predictive value of tests results must be established. The influence of renal disease on the analyte should be much greater than its biological variability under non-specific stresses. The results of using the test should benefit patients, taking into account the costs of false positive results and other costs to society that come from providing the test. Prospective studies needed to validate tests should be feasible and affordable. These studies could be facilitated by establishing a collaborative bank of urine samples linked to clinical data. Tests which are not used in clinical decision making are unimportant and of little value. Tests used in decision making should be evaluated as rigorously as the treatments that will be chosen based on the test results. PMID- 7869664 TI - New markers for the determination of GFR: iohexol clearance and cystatin C serum concentration. PMID- 7869665 TI - Serum cystatin C: a replacement for creatinine as a biochemical marker of GFR. PMID- 7869666 TI - Creatol and chronic renal failure. PMID- 7869667 TI - Assay of laminin fragments in the assessment of renal disease. PMID- 7869668 TI - Urinary enzymes and low molecular weight proteins as markers of tubular dysfunction. AB - Reference intervals of different tubular markers, that is, low molecular weight proteins and urinary enzymes, show divergent data and wide ranges. The problems in establishing reference intervals for the tubular markers are caused by the necessarily different analytical methods. Also, the general rules of determining reference limits as well as the numerous physiological variables influencing tubular function are often not sufficiently taken into consideration. Compared to blood components, urinary tubular markers show a wide variability of values. This is due to the fact that the excretion of enzymes and proteins into urine represents an excretion into an open system. The influences of variables like age, sex, physical exercise, different urine flow rates, and biorhythms are immediately reflected by changed excretion rates of tubular markers. The problems occurring when the second morning urine sample is being used as a "standardized" collection method and the basis to characterize tubular function by analyte/creatinine ratios are discussed in this paper. PMID- 7869669 TI - A marvel of colors and ingredients. The story of urine test strip. AB - The history of the urinary test papers does not being in the post-war period. As early as the 1880's some practitioners and pharmacists tried to replace the complicated wet-chemical procedures and apparatus by "dry chemistry." The first popular test paper for sugar and albumin originated in England in 1883. Dry reagents for proving hematuria have been available since the beginning of this century. Until the 1930s a wide palette of commercial urine tests with "modern" brand names was established. A methodological breakthrough was created by the spot test chemistry inaugurated by the Austrian, Fritz Feigl, about 1920. Using the capillary properties of filter paper in enhancing color reactions he founded a new area of analytical chemistry. Many of the pioneers were recruited from Jewish scientists. In this lecture is proposed that their emigration and banishment as well as the Second World War have stopped the development of urinary diagnostics on the European continent. In the post-war period the American industry succeeded to the leading position in the researching and marketing of test papers. In 1956, the triumphal progress of the "stick tests" began with the "Clinistix" (Ames Company, today Bayer Diagnostic). PMID- 7869670 TI - Varied value of urinary N-acetyl-beta-D-glucosaminidase isoenzyme B in males of reproductive age. AB - A reliable enzyme-linked immunosorbent assay designed to detect N-acetyl-beta-D glucosaminidase isoenzyme B (NAG-B) was used to determine distribution and variation of urinary NAG-B in normal and pathologic urine. NAG-B values varied over a much broader range in urine from male than in that from female subjects under different conditions of sampling. Because NAG-B values are markedly high in the semen (5800.2 micrograms/liter on the average), contamination of the urine with NAG-B from genital tissues occurs at urination, when it enters urine containing NAG-B of renal origin. The clinical significance of NAG-B and total NAG enzymatic activity as a renal tubular marker should be carefully evaluated when analyzing urine of males from reproductive age. PMID- 7869671 TI - Human intestinal versus tissue-nonspecific alkaline phosphatase as complementary urinary markers for the proximal tubule. AB - The availability of early biological markers of renal damage is important for the identification of risk factors and for starting therapeutic intervention in the reversible phase of renal pathology. The usefulness of such markers relies upon their capacity to detect alterations in distinct nephron segments. Using specific monoclonal antibodies against the intestinal isoenzyme of alkaline phosphatase (IAP) and against the tissue-nonspecific isoenzyme (TNAP), we demonstrated that IAP expression in the human kidney is restricted to the straight part of the proximal tubule (the S3 segment), whereas TNAP is expressed mainly in the proximal convoluted tubule (the S1 and S2 segments) but also in the S3 segment. This complementarity opens perspectives for IAP and TNAP as distinct proximal tubular markers, particularly for IAP, since there are no other markers available that are specific for the S3 segment. Based on these monoclonal antibodies, specific and easy to use enzyme-antigen immunoassay (EAIA) procedures were developed to detect IAP and TNAP in human urine samples. The detection limits are below the lowest enzyme activities found in the urine of normal subjects, the intra- and inter-assay variability is low, the analytical recovery approaches 100%, and EAIA enzyme activity values correlate with ELISA immunoreactivity values. Furthermore, easy urine sample preconditioning allows antigen preservation over an extended time period at 4 degrees and -80 degrees C. Using these assays, it could be demonstrated in more than 20 occupationally and environmentally exposed cohorts and clinical patient groups that urinary IAP is indeed a marker of early alterations in the S3 segment, and that it behaves largely independently from urinary TNAP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869672 TI - Disintegration and recovery of kidney membrane proteins: consequence of acute and chronic renal failure. PMID- 7869673 TI - To store urinary enzymes: how and how long? PMID- 7869674 TI - Changes in urinary enzymes and kidney-derived antigens after acute renal papillary necrosis in rats. PMID- 7869676 TI - Proteinuria and hypertension. AB - Albuminuria is more prevalent in patients with primary hypertension than in normotensive subjects of the general population. The presence of albuminuria predicts the presence of more severe target organ damage and is related to the risk of cardiovascular events. Preliminary results show albuminuria even in some normotensive individuals with a genetic risk of hypertension and in association with insulin resistance. While albuminuria is generally more frequent in the elderly, it is also found in young patients with mild to moderate primary hypertension. It is uncertain whether in these circumstances albuminuria indicates some "renal component" in the etiology of primary hypertension. Massive albuminuria may occur in subjects with "benign" nephrosclerosis. Whether albuminuria is a predictor of hypertensive renal damage requires further study. Albuminuria is reduced by antihypertensive treatment, but diverse effects on albuminuria are seen with different antihypertensive agents. PMID- 7869675 TI - Urinary excretion of cathepsin B and cystatins as parameters of tubular damage. AB - The urinary excretion of the lysosomal hydrolases cathepsin B and beta-N acetylglucosaminidase (beta-NAG) was compared with the tubular activities of these enzymes in remnant kidneys 16 weeks after subtotal nephrectomy (5/6 NX) or unilateral nephrectomy (UNX), as well as in kidneys from diabetic rats. In addition, the urinary excretion of the low-molecular weight protein cystatins, inhibitors of lysosomal cathepsins, was also followed in these animals. The urinary excretion of cathepsin B and beta-NAG was significantly enhanced in all three models of renal disease. The highest excretion rates for these enzymes were found in diabetic animals (cathepsin B: 4-fold; beta-NAG: more than a 10-fold increase over respective controls). In terms of tubular enzyme activities, tissue activities of both hydrolases were reduced in the remnant kidney after 5/6 NX, while in UNX and diabetes only cathepsin B activity was decreased. The urinary excretion of cystatins was enhanced in all three animal models, particularly in 5/6 nephrectomized rats, where a 40-fold increment over control animals was observed. Taken together, these findings indicate that there was severe tubular damage in the remnant kidney after 5/6 NX (reduced tubular enzyme activities, enzymuria and severely compromised tubular protein reabsorption). Furthermore, considerable enzymuria and disturbed protein reabsorption in early diabetes suggest tubular dysfunction before signs of glomerular damage become evident. PMID- 7869677 TI - Neopterin--its clinical use in urinalysis. AB - Increased amounts of neopterin are released during cellular immune response. Neopterin concentrations can be monitored in serum and urine of patients since neopterin is removed from the circulation by renal excretion. In allograft recipients, rising neopterin concentrations indicate rejection episodes early. Neopterin concentrations correlate with the extent and activity of viral infections, malignancies, and autoimmune diseases. We investigated excretion kinetics of neopterin in a rhesus monkey which received a high dose of neopterin intravenously. A sharp increase of urinary neopterin concentrations was observed, and from the data the half-life of neopterin in the circulation was estimated to be 90 minutes. By comparing urine and serum neopterin concentrations in HIV seropositive and seronegative human individuals, a strong correlation and similar diagnostic sensitivity between urine and serum values was observed. Thus, neopterin concentrations in serum or urine seem of equal value for diagnostic application as long as renal function is normal. PMID- 7869678 TI - Early urinary markers of target nephron segments as studied in cadmium toxicity. AB - A number of chemicals may adversely affect one or more of the anatomical structures of the kidney, such as the glomerulus, the tubular apparatus, the medullary, or interstitial cells. To recognize subclinical renal dysfunction, a battery of new, non-invasive tests was applied in comparison to established ones. The study on cadmium exposed subjects, performed within the framework of a collaborative European research project, exemplifies the concept of target selectivity within a nephron. One hundred seventy-two subjects were classified according to urinary cadmium excretion as controls (< 1.5 micrograms/g creatinine), or subjects with moderate or high cadmium body burden (1.5 to 5 micrograms/g creatinine, > 5 micrograms/g creatinine). Twenty-six urinary analytes (such as serum derived proteins, tubular enzymes, eicosanoids) and four plasma markers, related to the function or integrity of specific nephron segments, were investigated in a cross-sectional study. The group with the moderate cadmium body burden showed alterations of proximal tubular integrity, that is, increased excretion of tubular brush-border antigens. The group with higher cadmium body burden revealed an involvement of the whole nephron. The most prominent quantitative changes were found for the glomerular markers high molecular weight proteins, and thromboxane B2 and for the proximal tubular markers retinol binding protein, alpha 1-microglobulin, N-acetyl-beta-D glucosaminidase, and the intestinal alkaline phosphatase. A diagnostic approach to screen for nephrotoxicity due to environmental hazards like cadmium should include proximal tubular markers (alpha 1-microglobulin and tubular enzymes, that is, intestinal alkaline phosphatase) but the measurement of glomerular markers is also advisable. PMID- 7869680 TI - [Squint operation of the right or left eye?]. PMID- 7869679 TI - Early recognition of rejections in kidney transplant recipients: applying tests for kidney-derived urinary antigens. PMID- 7869681 TI - [15 years automated perimetry--where does the path lead?]. AB - 15 years ago the first fully automated perimeter became available, the Octopus 201, developed by Fankhauser in Bern. Some of the objections which were raised in those days against automated perimeters have turned out true, many, however, not. From todays perspective automated perimetry has brought tremendous advantages for clinical routine diagnosis. The essential power of automated perimetry is its ability to obtain quantitative data which can be processed statistically. The examination of the central visual field may be performed in a much more sophisticated way than by manual kinetic testing. Automated perimetry, however, also has its draw-backs, which are mostly due to mistakes or errors by the examiner, not so much to the method itself. For routine light-sense perimetry the upcoming years will give us faster and optimized testing strategies. Procedures for automated interpretation of visual field data will be developed. The interest in more complex perimetric test criteria goes on one hand into the direction of independence of disturbancies of the optical media (e.g. temporal criteria), on the other hand into the differentiation of various cell populations in the visual system (Blue/Yellow-Perimetry; Motion-Defined-Form etc.). For objective perimetry a powerful system for pattern-ERG and pattern-VECP with a spatial resolution comparable to standard perimetric tests is available. Also in these fields of perimetry the coming years will bring interesting and revolutionary new developments which will open new diagnostic dimensions. PMID- 7869682 TI - [Combined oblique muscle operation with transposition of the insertion in strabismus sursoadductorius]. AB - BACKGROUND: The combined superior oblique tendon tuck and inferior oblique recession is the method of choice for the treatment of congenital and acquired superior oblique muscle palsies with large vertical and cyclodeviations. An additional transposition of the insertions is indicated if the vertical deviation differs greatly from the excyclodeviation. PATIENTS AND METHODS: 38 patients who underwent combined oblique muscle surgery for congenital superior oblique muscle palsy were divided into 3 groups. Group A: 14 patients with small excyclodeviations in spite of large vertical deviations, even after diagnostic occlusion of 3 days. A superior oblique tendon tuck of 5 or 6 mm with transposition of the new insertion to the posterior margin of the original insertion was performed combined with a recession of the inferior oblique muscle of 5 or 6 mm with anterior displacement of 4-6 mm. Group B: 15 patients without a discrepancy between the vertical deviation and the cyclodeviation. They were treated with a conventional superior oblique tendon tuck of 5 or 6 mm combined with a recession of the inferior oblique muscle. Group C: 9 patients without a discrepancy between the vertical deviation and the cyclodeviation, but deviations smaller than in group B. A conventional superior oblique tendon tuck of 6 mm combined with a posterior tenotomy of the inferior oblique muscle was performed. The surgical effect was calculated as the difference between the preoperative deviation after diagnostic occlusion of 3 days and the postoperative deviations (1 week and 3 to 6 months). All angles of deviation were measured subjectively after dissociation of the binocular vision with a dark red filter in front of the fixating, not affected eye at 2.5 m distance using the Harms tangent screen. RESULTS: 3 months postoperatively, the vertical deviation was diminished in primary position by 12.1 degrees/6.8 degrees/6.8 degrees in groups A/B/C, in 25 degrees adduction of the affected eye by 18.4 degrees/13.8 degrees/9.5 degrees. The reduction of the cyclodeviation in primary position was 6.4 degrees/8.0 degrees/5.6 degrees. As a side effect a clinically insignificant, consecutive Brown syndrome occurred in each group. In each group a significant positive correlation between the preoperative deviation and the surgical effect was found. CONCLUSIONS: The combined superior oblique tendon tuck and inferior oblique recession with transposition of the insertions is a suitable method for a selective treatment of the vertical deviation and the cyclodeviation in congenital superior oblique palsy. PMID- 7869683 TI - [Role of segmental buckling surgery in treatment of stages B and C proliferative vitreoretinopathy detachment. A long-term follow-up]. AB - BACKGROUND: The following questions should be addressed: (1) Is minimal detachment surgery justified in treating detachments with preoperative PVR stage B or C? (2) Can this reattach the retina with stabilization or regression of PVR? MATERIALS AND METHODS: 72 PVR detachments stage B or C (38 C1, 11 C2, 1 C3) were treated by cryopexy, segmental buckling (n = 68) or balloon (n = 4) without drainage or vitrectomy. Reoperation (n = 10) was done without cerclage or vitrectomy. The follow-up of patients alive is 11 to 13 1/2 years and of all patients (31 died) x 7 1/2 years. RESULTS: After the primary operation the retina was reattached in 79%, partially in 15% and detached in 6%. An "early" redetachment (< or = 6 months postoperatively) occurred in 8.3%, no redetachment > 6 months to < 9 years and "late" redetachment (9-13 1/2 years postoperatively) in 2.8%. After reoperation (n = 10) the retina was reattached in 85%, partially in 3%, and detached in 12%. 34 eyes had delayed resorption (2 weeks to 18 months) with a residual concave detachment in area of starfolds and tractions, resulting in dry starfolds or their disappearance after months. Postoperatively there were no rubeosis iridis, no secondary glaucoma and no phthisis bulbi. Subsequent macular pucker developed in 12 eyes, which were not treated by vitreoretinal surgery. Six months postoperatively visual acuity was: 26x 20/60-20/25; 16x 20/200-20/100; 30x < or = 20/400 which was not statistically significant different (p = 0.549) after x 7 1/2 years. CONCLUSION: Primary treatment of a PVR detachment stage B or C1/C2 with cryopexy and segmental buckling and nondrainage seems justified to test for the chance of PVR-regression. The retina was reattached in 8 of 10 patients x 7 1/2 years postoperatively after primary operation without reoperation or vitrectomy and visual acuity was 20/60-20/25 in every third patient, thus implying a lack of late serious complications. PMID- 7869684 TI - [Visco-hydraulic irrigation of the lens cortex. A safe ECCE method]. AB - BACKGROUND: The safe and effective Hydrojet nucleus expression (Klin Monatsbl Augenheilkd 1993; 202:288-291) should be completed by a safe non traumatic and easy to perform method of cortex removal. MATERIAL AND METHODS: OPERATION TECHNIQUE: 8-mm tunnel incision, spiral capsulorhexis, hydrodissection and viscodissection of the nucleus, hydrojet nucleus expression. The lens cortex can be separated from the lens capsule by injection of hydroxypropylmethylcellulose (Metho), the viscoelastic substance acts as a wedge to separate the cortex from the capsule step by step. Finally the cortex is expressed by the injection of Metho. The capsule remains so clean, that often polishing is not necessary. PMMA lenses with an over all diameter of 10 or 11-mm and 7-mm optics were implanted. In 100 consecutive cases complications which occurred intraoperatively or within the following 2 days were listed. RESULTS: The following complications occurred: Hyphaema (2x, the blood disappeared spontaneously within 4-5 days), small cortex flake in the anterior chamber (2x), rhexis rim not intact (1x, nevertheless exact lens centration in the bag). No lesion of the capsule/zonule diaphragm, no fibrin reaction, no corneal edema. CONCLUSION: The method described is a safe method for ECCE. Capsulorhexis and tunnel incision are required. The method does not need any high technology equipment. PMID- 7869685 TI - [Normal flora of the human conjunctiva: examination of 135 persons of various ages]. AB - PURPOSE OF THE STUDY: Conjunctival flora is a prime suspect in searching for the cause of post-traumatic or post-operative ocular infections. Better information on its individual composition is therefore desirable. METHODS: 135 persons (66 women, 69 men) were examined during a period of 1 1/2 years. The youngest patient was 3 years old, the oldest 90. Both eyes of all patients were examined. RESULTS: Megasphaera elsdenii, Bacteroides ureolyticus, Bacteroides pneumosintes, Stomatococcus mucilaginosus, and group ANF Corynebacterium were isolated for the first time in the eye by this study. The latter was found so often that it can be ascribed the role of an aerobic indicator organism. Characteristic changes appear in the conjunctival flora at different stages of life. In particular, for example, the species spectrum of aerobic bacteria broadens with advancing age, and the population of aerobic bacteria increases in density. CONCLUSIONS: With increasing age aerobic cocci are found less frequently in favor of the Corynebacteria. The proportion of anaerobic cocci increases among the anaerobes, while Propionibacteria are demonstrated less frequently. The significance of the organisms found in conjunctiva by this study for the first time is still unclear. No qualitative or quantitative sex-specific influence on the development of conjunctival flora was found. PMID- 7869686 TI - [Painless infiltration anesthesia in eyelid surgery. An intraindividual randomized prospective study]. AB - BACKGROUND: Local anesthetic infiltration before lid surgery causes pain of varying degrees. To reduce the patient discomfort we have tested the effect of an initial injection of deluted anesthetic prior to the infiltration anesthesia. PATIENTS AND METHODS: During August 1993 and April 1994 thirteen patients, 21 to 81 years of age had bilateral lid surgery (4 female; 9 male). Two injection techniques were studied in disease patients intraindividually. Part of the local anesthetic was deluted 1:10 with saline and initially injected on one side only. Three minutes later infiltration with 2-5 ml of full-strength 2% mepivacaine with adrenaline 1:200,000 was performed on both sides. Obvious signs of pain were documented and patients were questioned about their discomfort (score 0-3). RESULTS: Five patients were operated for bilateral ectropium (lateral canthal sling procedure 4, Lazy-T 1), seven patients for dermatochalasis and one patient for brow ptosis. All thirteen patients ranked the technique with the initial injection of deluted local anesthetic significantly less painful. 9 of 13 patients had painless local anesthetic infiltration. Only 4 patients reported minor discomfort during injection of the diluted anesthetic. Onset time and duration of anesthesia was identical in both groups. CONCLUSION: The initial injection of a 1:10 diluted local anesthetic allows a significant reduction of pain during infiltration anesthesia before lidsurgical procedures. While pH buffering with bicarbonate may cause permanent skin pigmentation, dilution with physiological saline is an effective and inexpensive alternative. With this technique even in children local anesthesia becomes possible. PMID- 7869687 TI - [Clinical decision aids using ultrasound biomicroscopy]. AB - Ultrasound biomicroscopy (UBM) allows high-resolution imaging of the anterior segment due to ultrasound transducers between 50 and 100 MHz. At present stage of experience, mainly analysis of iris and ciliary body structures seem to be clinically rewarding. This is demonstrated by two similar looking tumors, involving the chamber angle. By means of UBM it was possible to differentiate between cystic and solid growths and to assess tumor extensions. PMID- 7869688 TI - [Non-syphilitic interstitial keratitis and inner ear deafness in the initial phase of Wegener's granulomatosis]. AB - BACKGROUND: The aim of the present report is to briefly discuss the possible underlying diseases in a syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms. PATIENT: A 46-year-old patient presented with interstitial keratitis, vestibuloauditory hearing reduction and necrotising atrophy of the nasal septum. RESULTS: Clinical tests for lues, tuberculosis, sarcoidosis and autoimmune diseases were negative. CONCLUSION: For clinical aspects Cogan's syndrome in association with an initial phase of Wegener's granulomatosis are discussed as possible underlying diseases. PMID- 7869689 TI - [200th birthday of Maximilian Josef von Chelius (1794-1876). First chairman of surgery and ophthalmology in Heidelberg]. PMID- 7869690 TI - ["The Retina of the Vertebrates" by Santiago Ramon y Cajal--100 years in German translation]. AB - 1894 Richard Greeff, a young scientist at the University of Berlin, translated the book "The retina of vertebrates" of Santiago Ramon y Cajal into German. Greeff himself had already applied the Golgi-Cajal-Chromic-Silver dye to the retina and was enthusiastic about the results of Cajal. He interrupted his own investigations in favour of translating the book into German. Cajal demonstrates that the retina contains individual neurons contradicting the theory at that time, that the nervous system is a synzythium. This new theory had a great impact on German science although it took years to be accepted unanimously. PMID- 7869691 TI - [Meeting of the German Society of Intraocular Lens Implantation. 19-20 March 1994, Berlin. Abstracts]. PMID- 7869692 TI - [Comments on the editorial by G. Kommerell "Treatment of optic neuritis with corticosteroids"]. PMID- 7869693 TI - [Presentation of the Theodor Axenfeld Award to Prof. Dr. h. c. Franz Frankhauser during the opening celebration of the 92nd Congress of the German Society of Ophthalmology 25 September 1994 in Mannheim]. PMID- 7869694 TI - Kidney function in congestive heart failure. PMID- 7869695 TI - Managed care for the frail elderly: the PACE Project. PMID- 7869696 TI - Renal colic due to Henoch-Schonlein purpura. AB - A six-year-old boy with Henoch-Schonlein purpura (HSP) presented with renal colic and the passage of tubular-shaped blood clots in the urine. The authors suggest that the renal colic was due to a ureteritis. Ureteritis in patients with HSP may be more common than is generally appreciated. PMID- 7869697 TI - You can do something about adolescent substance use & abuse: a practitioner's guide to adolescent alcohol and other drug prevention. PMID- 7869698 TI - Third World cardiology: back to the basics. PMID- 7869699 TI - "The rights of the child" revisited. PMID- 7869700 TI - Rationalizing decisions for diagnostic testing. PMID- 7869701 TI - South Carolina malpractice suit found in favor of the defendant physician. PMID- 7869702 TI - Modern therapeutic interventional techniques. PMID- 7869703 TI - Age and the false-consensus effect. AB - Israeli participants in four age groups (older adolescents, adults, residents of an old-age home, and older participants in a university program) answered a 12 item false-consensus questionnaire and Davis's (1980) Interpersonal Reactivity Index measuring empathy-egocentrism. The false-consensus effect (FCE) was found in all four age groups. The effect was significantly weaker among the older students, which was also the group lowest on egocentrism. Older adolescents were more egocentric than adults, who were less egocentric than residents of the old age home, who were the highest on egocentrism. No correlation was found between the strength of the FCE and the egocentrism score. PMID- 7869704 TI - Responding to sexual discrimination: the effects of societal versus self-blame. AB - Although self-blame has been considered to be a useful coping tool for victims, its benefits within the context of group discrimination are equivocal. The present research hypothesized that women encouraged to engage in self-blame for sex discrimination would be more likely to endorse accepting the situation or to endorse the use of individual, normative actions. In contrast, women encouraged to engage in societal blame for sex discrimination would be more likely to participate in nonnormative actions aimed at enhancing the status of women as a group. Female students in Canada were subjected to a situation of discrimination and were encouraged to blame either themselves or society. They were then given the opportunity to respond to the discrimination by endorsing various actions. A profile analysis of the endorsed actions indicated that the women encouraged to blame themselves were most likely to endorse accepting the situation, whereas the women encouraged to blame society endorsed nonnormative individual confrontation. PMID- 7869705 TI - The effect of self-presentation on social value orientation. AB - Social-value orientations in interdependence situations are expected to be influenced by self-presentational concerns because in contrast to proself orientations (individualism and competition), prosocial orientations (cooperation, altruism, equality, and maximin) tend to make a more positive impression on others. In the present study, the influence of self-presentation on social orientation was inhibited by means of a bogus pipeline procedure. Dutch University students in a bogus pipeline condition displayed less prosocial and more proself orientations than students in a condition in which no bogus pipeline was used. PMID- 7869706 TI - The temporal relationship between perceived competence and self-determined motivation. AB - Although perceived competence is generally considered a determinant of motivation, little research has actually studied the relation between the two constructs on a longitudinal basis and in natural settings. This was the purpose of the present study. Canadian male adolescent hockey players (N = 64) in their first year at an elite level completed a questionnaire 2 weeks into the hockey season (T1) and at the end of the regular season (T2), assessing perceived competence and self-determined motivation at both times. The results partially support the hypothesis that, over time, perceived competence determines motivation (rather than the reverse) but do not exclude the possibility that, with time, motivation may also influence perceptions of competence. PMID- 7869707 TI - Relieving stress through value-rich work. AB - On the basis of Herzberg, Mausner, and Snyderman's (1959) motivator-hygiene theory, it was hypothesized that intrinsic but not extrinsic work values would be inversely related to stress. Also investigated was the question of which work values provide the most relief from stress. Elementary school teachers and administrators (N = 607) from nine school boards in southern Ontario completed a survey that included Pines, Aronson, and Kafry's (1981) stress scale and Elizur's (1984) work values scale. Almost all of the 12 intrinsic work values investigated were negatively correlated with stress, but the 4 extrinsic work values studied were not consistently related to stress. Five work values explained 11% of the variance in physical stress, 9 work values explained 22% of the variance in emotional stress, and 6 work values explained 26% of the variance in mental stress. Four work values emerged as meaningful predictors of all three types of stress: being esteemed by others, achieving through work, doing meaningful work, and being able to use one's knowledge and abilities. PMID- 7869708 TI - Measuring environmental/biological attribution: a fundamental dimension? AB - Explanations for behaviors that emphasize the importance of biological or environmental factors have been a major theme in psychological discourse, yet they have not been adequately explored as attributional styles with distinct correlates. The present two studies examined this dimension of attribution through the systematic development and validation of the Environmental/Biological Attribution Scale (EBAS). A total of 602 Canadian university students took part in the research project. The research confirmed four hypotheses: Biologically oriented attributional styles were significantly correlated with the same styles as measured by an alternate form (r = .76), with authoritarianism (r = .25), and with racism (r = .15). Environmentally oriented attributional styles were significantly correlated with attributions concerning the importance of strength of will (r = .39). PMID- 7869709 TI - Smoking and satisfaction and motivations: a comparison of men and women. PMID- 7869710 TI - Attitudes about suicide among the Yoruba of Nigeria. PMID- 7869711 TI - Interactive effects of work motivation and personal control on employee job performance and satisfaction. PMID- 7869712 TI - Investigation of vibration characteristics of the ligamentous lumbar spine using the finite element approach. AB - A nonlinear, three-dimensional finite element model of the ligamentous L4-S1 segment was developed to analyze the dynamic response of the spine in the absence of damping. The effects of the upper body mass were simulated by including a mass of 40 kg on the L4 vertebral body. The modal analyses of the model indicated a resonant frequency of 17.5 Hz in axial mode and 3.8 Hz in flexion-extension mode. Accordingly, the predicted responses for the cyclic load of -400 +/- 40 N applied at four different frequencies (5, 11, 16.5, and 25 Hz) were compared with the corresponding results for axial compressive static loads (-360, and -440 N). As compared to the static load cases, the predicted responses were higher for the cyclic loading. For example, the effect of cyclic load at 11 Hz was to produce significant changes (9.7-19.0 percent) in stresses, loads transmitted through the facets, intradiscal pressure (IDP), disk bulge, as compared to the static load predictions. The responses were found to be frequency dependent as well; supporting the in vivo observations of other investigators that the human spine has a resonant frequency. For example, the 11 Hz model (DYN11) compared to the DYN5 model showed an increase in majority of the predicted parameters. The parameters showed an increase with frequency until 17.5 Hz (resonant frequency of the model); thereafter a decrease at 25 Hz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869713 TI - Nondestructive detection of cartilage degeneration using electromechanical surface spectroscopy. AB - We have constructed an electrokinetic surface probe capable of applying small sinusoidal currents to the surface of articular cartilage and measuring the resulting current-generated stress with a piezoelectric sensor. Using the probe, we have characterized the electromechanical response of excised discs of normal and chemically modified adult bovine femoropatellar groove cartilage. The measured stress amplitude was proportional to the applied current density and inversely proportional to the excitation frequency, consistent with a poroelastic model. As a function of bath pH, the stress amplitude exhibited a minimum in the range pH 2.4-2.8 and the phase underwent an abrupt 180 degrees transition in the same range, consistent with an electrokinetic mechanism as the origin of the current-generated mechanical stress. Digestion of the tissue with trypsin resulted in a progressive loss of highly charged proteoglycan molecules from the tissue, with a concomitant decrease in the measured stress amplitude. These results support the feasibility of surface measurements as a means of assessing electromechanical transduction in cartilage and of detecting subtle molecular level degradative changes in the extracellular matrix. This technique of surface spectroscopy provides a new means of nondestructively measuring the material properties of cartilage on intact joints and detecting degradative changes such as those seen in the earliest stages of osteoarthritis. PMID- 7869714 TI - Effects of fit and bonding characteristics of femoral stems on adaptive bone remodeling. AB - Bone atrophy caused by stress-shielding may cause serious complications for the long-term fixation of hip stems. In particular, uncemented total hip arthroplasty is threatened by this problem, because the stems are usually larger and, as a consequence, stiffer than those of cemented implants. In the present study, the effects of fit and bonding characteristics of femoral hip stems were investigated, using the (nonlinear) finite element method in combination with adaptive bone remodeling theory to predict the bone density distribution in a bone or bone/implant configuration. Unknown parameters used in the theory, such as a reference equilibrium loading stimulus and a threshold (dead) zone of this stimulus, were established (triggered) by using the method to predict the density distributions in the natural femur and around fully coated uncemented implants. The computer simulation method can provide long term predictions of remodeling patterns around various implant configurations. Several cases were analyzed, whereby the coating conditions (fully, partly, or noncoated) and the fit characteristics (press fitted or overreamed) were varied. The computer predictions showed that partly coating can only significantly reduce bone atrophy relative to fully coated stems, when the coating is applied at a small region at the utmost proximal part of the stem. For smooth press-fit stems the predicted amount of bone loss (35 percent in the proximal medial region) was less than for a one-third proximally coated or a fully coated stem (50 to 54 percent predicted bone loss in the proximal medial region).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869715 TI - A finite element analysis of the human temporomandibular joint. AB - A 2-D finite element model of the human temporomandibular joint (TMJ) has been developed to investigate the stresses and reaction forces within the joint during normal sagittal jaw closure. The mechanical parameters analyzed were maximum principal and von Mises stresses in the disk, the contact stresses on the condylar and temporal surfaces, and the condylar reactions. The model bypassed the complexity of estimating muscle forces by using measured joint motion as input. The model was evaluated by several tests. The results demonstrated that the resultant condylar reaction force was directed toward the posterior side of the eminence. The contact stresses along the condylar and temporal surfaces were not evenly distributed. Separations were found at both upper and lower boundaries. High tensile stresses were found at the upper boundaries. High tensile stresses were found at the upper boundary of the middle portion of the disk. PMID- 7869716 TI - Analysis of role of bone compliance on mechanics of a lumbar motion segment. AB - A large deformation elasto-static finite element formulation is developed and used for the determination of the role of bone compliance in mechanics of a lumbar motion segment. This is done by simulating each vertebra as a deformable body with realistic material properties, as a deformable body with stiffer or softer mechanical properties, as a single rigid body, or finally as two rigid bodies attached by deformable beams. The single loadings of axial compression, flexion moment, extension moment, and axial torque are considered. The results indicate the marked effect of alteration in bone material properties on biomechanics of lumbar segments specially under larger loads. The biomechanical studies of the lumbar spine should, therefore, be performed and evaluated in the light of such dependency. A model for bony vertebrae is finally proposed that preserves both the accuracy and the cost-efficiency in nonlinear finite element analyses of spinal multi-motion segment systems. PMID- 7869717 TI - Optimization of the contact damping and stiffness coefficients to minimize human body vibration. AB - In this paper, a lumped mass human model is used to minimize the energy absorption at the feet/hip level when the body is subjected to vertical vibration. The contact forces are assumed unknown. By coupling the dynamic response of the body with certain objective criteria, the optimum damping and stiffness coefficients of shoes/chairs are sought. The optimization technique is based on the quasi-Newton and finite-difference gradient method and is used to seek optimum coefficients of the contact forces in the solution of the body's response in the frequency domain. The criteria of acceleration, displacement and internal forces response area swept for a range of 0-15 Hz form the basis of our simulation study. In the seated/standing postures it is found that for each criteria the frequency response shifts the peak of resonance of each body segment response from 4.5/3.67 Hz to 2.5/2.255 Hz. In addition, the total energy reduces drastically when the contact conditions are optimum. The method presented in this paper is useful in modeling the medium of contacts and especially in controlling the effects of human body vibration. PMID- 7869718 TI - A biphasic poroelastic analysis of the flow dependent subcutaneous tissue pressure and compaction due to epidermal loadings: issues in pressure sore. AB - A layer of skin and subcutaneous tissue on a bony substratum was modeled as a homogeneous layer of biphasic poroelastic material with uniform thickness. The epidermal surface and the bony interface were taken to be impervious. The soft tissue on the bony interface was assumed either fully adhered or completely free to slide on the bone. The cases for surface pressure loadings and displacement controlled indentations were simulated. The resultant biomechanical responses of the layer, including the transient tissue hydrostatic pressure and the tissue compaction, were presented. A new hypothesis is offered to interpret the threshold pressure-time curve for pressure sores in term of the time required for a particular area in the tissue layer to reach a critical compaction for a given level of applied pressure. PMID- 7869719 TI - A fiber matrix model for the growth of macromolecular leakage spots in the arterial intima. AB - A new model is presented for the growth of cellular level macromolecular leakage spots in the arterial intima. The theoretical approach differs from the recent study by Yuan et al. [19] in that it directly models and calculates the intimal transport parameters based on Frank and Fogelman's [22] ultrastructural observations of the extracellular subendothelial proteoglycan matrix that their rapid freeze etching technique preserves (see Addendum). Using a heterogeneous fiber matrix theory, which includes proteoglycan and collagen components, the model predicts that the Darcy permeability Kp and macromolecular diffusivity D of the subendothelial intima is two orders of magnitude larger than the corresponding values measured in the media, and supports the observations in Lark et al. [24] that the proteoglycan structure of the intima differs greatly from that of the media. Numerical results show that convection parallel to the endothelium is a very significant transport mechanism for macromolecules in the intima in a large region of roughly 200 microns diameter surrounding the leaky cleft. The predictions of the new model for the early-time spread of the advancing convective-diffusive front from the leakage spots in the intima are in close agreement with our experimental measurements for the growth of HRP spots in [20]. The regions of high concentration surrounding the leaky cell, however, are much more limited and cover an area that is typically equivalent to 20 cells. This prediction is consistent with the recent measurements of Truskey et al. for LDL spot size in rabbit aorta [21] and the hypothesis advanced in [19] that there is a colocalization of subendothelial liposome growth and cellular level leakage. Finally, comparison of predicted and experimentally-measured average LDL concentration in leakage spots strongly suggests that there is significant local molecular sieving at the interface between the fenestral openings in the internal elastic lamina and the media. PMID- 7869720 TI - A scaling law for wall shear rate through an arterial stenosis. AB - Atherosclerosis of the human arterial system produces major clinical symptoms when the plaque advances to create a high-grade stenosis. The hemodynamic shear rates produced in high-grade stenoses are important in the understanding of atheromatous plaque rupture and thrombosis. This study was designed to quantify the physiologic stress levels experienced by endothelial cells and platelets in the region of vascular stenoses. The steady hemodynamic flow field was solved for stenoses with percent area reductions of 50, 75, and 90 percent over a range of physiologic Reynolds numbers (100-400). The maximum wall shear rate in the throat region can be shown to vary by the square root of the Reynolds number. The shear rate results can be generalized to apply to a range of stenosis lengths and flow rates. Using dimensions typical for a human carotid or coronary artery, wall shear rates were found to vary from a maximum of 20,000 s-1 upstream of the throat to a minimum of -630 s-1 in the recirculation zone for a 90 percent stenosis. An example is given which illustrates how these values can be used to understand the relationship between hemodynamic shear and platelet deposition. PMID- 7869721 TI - Transient behavior analysis of a mechanical monoleaflet heart valve prosthesis in the closing phase. AB - In this paper, an analysis of the dynamics in the closing phase of the occluder of a mechanical monoleaflet heart valve prosthesis is presented. The dynamic analysis of the fluid in the vicinity of the occluder was based on the control volume approach. The backflow velocity of the fluid was computed by applying the continuity and momentum equations in the unsteady state. By considering the fluid pressure and gravity as external forces acting on the occluder, the moment equilibrium on the occluder was employed to analyze the motion of the occluder during closing and the force of impact between the occluder and the guiding struts. The computed magnitudes of the occluder tip velocities, as well as the backflow of the fluid during the closing phase using this model, were in agreement with previously reported experimental measurements. The maximum impact force between the occluder and guiding struts of 140-280 N was determined to occur during the initial impact for a duration of 35-45 microseconds. The results of such model studies may be extended for the analysis of the endurance limit of the valve prostheses as well as to determine the mechanical stresses on the formed elements and the incipience of cavitation bubbles during the closing phase of the valve function. PMID- 7869722 TI - A method for real-time in vitro observation of cavitation on prosthetic heart valves. AB - A method for real-time in vitro observation of cavitation on a prosthetic heart valve has been developed. Cavitation of four blood analog fluids (distilled water, aqueous glycerin, aqueous polyacrylamide, and aqueous xanthan gum) has been documented for a Medtronic/Hall prosthetic heart valve. This method employed a Penn State Electrical Ventricular Assist Device in a mock circulatory loop that was operated in a partial filling mode associated with reduced atrial filling pressure. The observations were made on a valve that was located in the mitral position, with the cavitation occurring on the inlet side after valve closure on every cycle. Stroboscopic videography was used to document the cavity life cycle. Bubble cavitation was observed on the valve occluder face. Vortex cavitation was observed at two locations in the vicinity of the valve occluder and housing. For each fluid, cavity growth and collapse occurred in less than one millisecond, which provides strong evidence that the cavitation is vaporous rather than gaseous. The cavity duration time was found to decrease with increasing atrial pressure at constant aortic pressure and beat rate. The area of cavitation was found to decrease with increasing delay time at a constant aortic pressure, atrial pressure, and beat rate. Cavitation was found to occur in each of the fluids, with the most cavitation seen in the Newtonian fluids (distilled water and aqueous glycerin). PMID- 7869723 TI - Analysis of flow in a two-dimensional collapsible channel using universal "tube" law. AB - This paper presents an extension of the previous analyses on the collapsible tube flow problem using a simplified model based on a two-dimensional channel conveying a one-dimensional flow. The main objective of the paper is to exploit the static and dynamic behavior of the model, by comparing with available experimental data and examining the accuracy of calculated results obtained for different numerical resolutions. The main revision from the previous analyses is the incorporation of a universal "tube" law that is valid for a wide range of positive and negative transmural pressure. Most of the numerical results agree qualitatively with the experimental observations. Self-excited high-frequency oscillation with very small amplitude of the membrane wall is however, predicted to occur in a flow range where the slope of the pressure drop curve is positive. It is seen that the high-frequency oscillation is associated with the motion of the separation point of the flow. PMID- 7869724 TI - Transition to turbulence in pulsatile flow through heart valves--a modified stability approach. AB - The presence of turbulence in the cardiovascular system is generally an indication of some type of abnormality. Most cardiologists agree that turbulence near a valve indicates either valvular stenosis or regurgitation, depending on the phase of its occurrence during the cardiac cycle. As no satisfying analytical solutions of the stability of turbulent pulsatile flow exist, accurate, unbiased flow stability criteria are needed for the identification of turbulence initiation. The traditional approach uses a stability diagram based upon the stability of a plane Stokes layer where alpha (the Womersley parameter) is defined by the fundamental heart rate. We suggest a modified approach that involves the decomposition of alpha into its frequency components, where alpha is derived from the preferred modes induced on the flow by interaction between flow pulsation and the valve. Transition to turbulence in pulsatile flow through heart values was investigated in a pulse duplicator system using three polymer aortic valve models representing a normal aortic valve, a 65 percent stenosed valve and a 90 percent severely stenosed valve, and two mitral valve models representing a normal mitral valve and a 65 percent stenosed valve. Valve characteristics were closely simulated as to mimic the conditions that alter flow stability and initiate turbulent flow conditions. Valvular velocity waveforms were measured by laser Doppler anemometry (LDA). Spectral analysis was performed on velocity signals at selected spatial and temporal points to produce the power density spectra, in which the preferred frequency modes were identified. The spectra obtained during the rapid closure stage of the valves were found to be governed by the stenosis geometry. A shift toward higher dominant frequencies was correlated with the severity of the stenosis. According to the modified approach, stability of the flow is represented by a cluster of points, each corresponding to a specific dominant mode apparent in the flow. In order to compare our results with those obtained by the traditional approach, the cluster of points was averaged to collapse into a single point that represents the flow stability. The comparison demonstrates the bias of the traditional stability diagram that leads to unreliable stability criteria. Our approach derives the stability information from measured flow phenomena known to initiate flow instabilities. It differentiates between stabilizing and destabilizing modes and depicts an unbiased and explicit stability diagram of the flow, thus offering a more reliable stability criteria. PMID- 7869725 TI - Steady inspiratory flow in a model symmetric bifurcation. AB - Flow in a bifurcating tube system typifying a major bronchial bifurcation is studied experimentally with a two color, two velocity component laser Doppler anemometer. The flow loop is composed of a pumping station, flow stratifiers and a constant head pressure tank; it can accommodate steady, pulsatile or oscillatory flow. The test section is a symmetric bifurcation of constant cross sectional area and has a branching angle of 70 deg. The test section is a cast of clear silicon rubber in a plexiglass mold that was milled on a numerically controlled milling machine. The flow division ratio from the parent to daughter branches is about unity. Steady flow results that model the inspiratory phase at Reynolds numbers of 518, 1036 and 2089, corresponding to Dean numbers of 98, 196 and 395, show that in the bifurcation plane velocity profiles in the daughter branches are skewed toward the inner wall. In the transverse plane, "m" shaped velocity profiles are found with low velocity at the center. Secondary flow patterns, which are responsible for such phenomena, are first observed at the axial position where the flow begins to turn. Flow separation was not observed at any point in the bifurcation. PMID- 7869726 TI - Additional pressure drop at a bifurcation due to the passage of flexible disks in a large scale model. AB - The flow of red blood cells (RBC) through a microvascular capillary bifurcation was modeled in a large scale system in which rigid circular tubes and bifurcations (diameter = .95 cm) simulated capillaries and capillary bifurcations, flexible disks (undeformed diameter = 0.75 cm) simulated RBC and glycerol simulated plasma. At low Reynolds numbers (0.01 to 0.1), pressure drop was measured in the tubes upstream and downstream from the bifurcation as well as across the bifurcation itself, for various flow splits at the bifurcation while the inflow in the upstream tube was held constant. Pressure gradient across the bifurcation is taken to be the average of the upstream and downstream pressure gradients if the additional pressure drop at the bifurcation due to the partitioning of flow and disks is negligible. For the case of glycerol alone, the ratio of pressure gradient (G) at the bifurcation to the one at the upstream region was always greater than expected and reached 1.14 when the flow in the side branch was zero. With introduction of flexible disks into the system, G at the bifurcation was as much as 10 times the G at the upstream region as disks came in contact with, or close to, the dividing line of the bifurcation and paused momentarily before they entered one or the other side of the bifurcation. The largest G was for even flow split at the bifurcation and the smallest G was for the case where the flow in the side branch was smallest. Therefore, for the range of tube hematocrits (0-30 percent) and flow splits tested here, a significant additional pressure drop at the bifurcation is observed. PMID- 7869727 TI - A junction-orifice-fiber entrance layer model for capillary permeability: application to frog mesenteric capillaries. AB - The recent serial section electron microscopic studies by Adamson and Michel (1993) on microves gels of frog mesentery have revealed that the large pores in the junction strand of the interendothelial cleft are widely separated 150 nm wide orifice-like breaks whose gap height 20 nm is the same as the wide part of the cleft. In this paper a modified version of the model in Weinbaum et al. (1992) is first developed in which this orifice structure is explored in combination with a random or ordered fiber matrix layer that is at the luminal surface and/or occupies a fraction of the wide part of the cleft. This basic orifice model predicts that for the measured Lp to be achieved the fiber layer must be confined to a relatively narrow region at the entrance to the cleft where it serves as the primary molecular filter. The model provides a much better fit of the permeability P for intermediate size solutes between 1 and 2 nm radius than the previous model in Weinbaum et al., where the junction strand breaks were treated as finite depth circular or rectangular pores, but like the previous model significantly underestimates P for small ions. However, it is shown that if a small frequent pore of 1.5 nm radius with characteristic spacing comparable to the diameter of the junction proteins or a continuous narrow slit of approximately 1.5 to 2.3 nm gap height is also present in the continuous part of the junction strand, small ion permeability can also be satisfied. The 1.5 nm radius pore does not significantly change Lp, whereas the continuous narrow slit provides a contribution to Lp that is comparable to, or in the case of the 2.3 nm slit greater than, the widely spaced 150 nm orifices. Thus, for the narrow slit the contribution to Lp from the orifices can be as low as 1.0 x 10(-7) cm/s/cm H2O and it is also possible to satisfy the 2.5 fold increase in permeability that occurs when the matrix is enzymatically removed from the luminal side of the cleft, Adamson (1990). The likelihood of each of these cleft structures is discussed. PMID- 7869728 TI - Hemolysis during membrane plasma separation with pulsed flow filtration enhancement. AB - The use of pulsed blood flow in membrane plasmapheresis permits enhancement of plasma filtration yet may result in high levels of hemolysis due to large increases in instantaneous transmembrane pressure (TMP). This work investigates the occurrence of hemolysis as a function of TMP and wall shear rates (gamma w) for both steady and pulsed blood flow conditions. Two types of hollow fiber filters with identical polypropylene membranes but different lengths and membrane areas (0.1 and 0.25 m2) were tested. Fresh citrated bovine blood was circulated through the fibers at various blood flowrates and TMP in a single pass circuit using a pulsation generator, made of a single roller peristaltic pump. The free hemoglobin concentration of the plasma, Hbm, was measured from permeate samples collected at each set of TMP and gamma w conditions. It was found that the net hemolysis generated by the filtration was proportional to the membrane area. This justified the introduction of an hemolysis index, IH, equal to the plasma hemoglobin per unit membrane area. The boundary for the occurrence of hemolysis was thus defined by setting IH = 30 mg/dl.m2. For both steady and pulsed flow conditions the hemolysis boundaries were found to be straight lines in the TMP gamma w plane. They were identical for the two filters under steady flow but different for pulsed flow. At the same time mean wall shear rates hemolysis occurred at a lower time mean TMP under pulsed flow conditions than under steady flow conditions. PMID- 7869729 TI - Formulation of a statistical model of heat transfer in perfused tissue. AB - A new model of steady-state heat transport in perfused tissue is presented. The key elements of the model are as follows: (1) a physiologically-based algorithm for simulating the geometry of a realistic vascular tree containing all thermally significant vessels in a tissue; (2) a means of solving the conjugate heat transfer problem of convection by the blood coupled to three-dimensional conduction in the extravascular tissue, and (3) a statistical interpretation of the calculated temperature field. This formulation is radically different from the widely used Pennes and Weinbaum-Jiji bio-heat transfer equations that predict a loosely defined local average tissue temperature from a local perfusion rate and a minimal representation of the vascular geometry. Instead, a probability density function for the tissue temperature is predicted, which carries information on the most probable temperature at a point and uncertainty in that temperature due to the proximity of thermally significant blood vessels. A sample implementation illustrates the dependence of the temperature distribution on the flow rate of the blood and the vascular geometry. The results show that the Pennes formulation of the bio-heat transfer equation accurately predicts the mean tissue temperature except when the arteries and veins are in closely spaced pairs. The model is useful for fundamental studies of tissue heat transport, and should extend readily to other forms of tissue transport including oxygen, nutrient, and drug transport. PMID- 7869730 TI - Considerations in applying dynamic programming filters to the smoothing of noisy data. AB - Dynamic programming techniques are useful in smoothing and differentiating noisy data signals according to an optimization criterion and the results are generally quite robust to noise spectra different from that assumed in the construction of the filter. If the noise properties are sufficiently different, however, the generalized cross-validation function used in the optimization can exhibit either multiple minima or no minima other than that corresponding to an insignificant amount of smoothing; in these cases, the smoothing parameter desired by the user typically does not lie at the global minimum of the generalized cross-validation function, but at some other point on the curve which can be identified heuristically. I present two cases to demonstrate this phenomenon and describe what measures one can take to ensure that the desired smoothing parameter is obtained. PMID- 7869731 TI - Evaluation by 24-hour ambulatory blood pressure monitoring of efficacy of benazepril 20 mg plus hydrochlorothiazide 25 mg fixed combination as compared to captopril 50 mg [corrected] plus hydrochlorothiazide 25 mg fixed combination in treating mild to moderate hypertension: a double-blind, within-patient, placebo controlled study. AB - In a double-blind, placebo-controlled, three-period cross-over, randomized study we evaluated the efficacy and tolerability of a fixed combination of benazepril 20 mg and hydrochlorothiazide 25 mg (BN + HCT) as compared with the fixed combination of captopril 50 mg and hydrochlorothiazide 25 mg (CP + HCT) by ambulatory blood pressure monitoring (ABPM) in patients with mild to moderate hypertension. Eighteen outpatients, 16 men and 2 women aged 41-58 years, were randomized to receive BN + HCT, CP + HCT, or placebo, all administered once daily for 4 weeks according to a three-period cross-over arranged in a 3 x 3 latin square design. Patients were checked after an initial 3-week washout period and every 4 weeks thereafter. At each visit, 24-h ABPM was performed by a noninvasive device (Spacelabs 5300); causal BP and heart rate (HR) were also measured. Both fixed combinations had a clear-cut antihypertensive effect in comparison with placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869732 TI - Fractal geometry study of DNA binding proteins. AB - The main aim of this paper is to search for three-dimensional structure homology between DNA-binding proteins. The run of a protein's main chain is depicted by a sequence, which is constituted by the fractal indices, where each index describes how twisted or extended a partial protein segment is. Two proteins are compared by constructing a dot matrix between two such sequences, and the matrix is searched for dot-concentrated rectangles which is an indication of tertiary homology. This new method is applied to DNA-binding proteins which are selected from Brookhaven Protein Data Bank, among which most contain a helix-turn-helix motif. The dot-matrix shows that there is tertiary homology between two motifs. Other interesting results are also presented in this paper. PMID- 7869733 TI - Evolutionary optimization of enzyme kinetic parameters; effect of constraints. AB - The distribution of the kinetic parameters of enzymic reactions is theoretically studied, on the assumption that, during evolution, the increase of reaction rates was an important target of natural selection. In extension of previous work on the optimization of enzyme kinetic parameters, the influence of constraints concerning upper limits of the individual rate constants is analyzed. The concept of "evolutionary effort" is applied to derive an expression for the cost function, leading to an overall upper limit for the values of the rate constants. The resulting optimization problem is solved for ordered mechanisms involving different numbers of elementary steps. It is shown that the optimum for the enzyme kinetic parameters strongly depends on the concentrations of the reactants. Low reactant concentrations lead generally to a tight binding of the reactants, while high concentrations result in a weak binding, favouring the rate constants of the other steps. In particular, states of maximum activity are not always characterized by maximal values of second-order rate constants. The results support the hypothesis that there is a mutual adaptation of Michaelis constants and reactant concentrations in an evolutionary timescale. In the limit of infinite values of the exponent of the cost function the results of the present "overall limit model" turn into the results of a model which takes into account individual upper limits for rate constants ("separate limit model"). The distributions of optimal rate constants are discussed in terms of free-energy profiles. The model is applied to the interpretation of the kinetic data of triosephosphate isomerase and inorganic pyrophosphatase. PMID- 7869734 TI - Koinophilia replaces random mating in populations subject to mutations with randomly varying fitnesses. AB - Koinophilia, the avoidance of sexual mates bearing strange phenotypic features, or displaying odd behaviour, would, if it evolved, profoundly influence the evolutionary process. A stochastic computer model was therefore devised to investigate the evolution of an initially rare koinophilic trait in panmictic populations, subject to mutations with randomly varying fitnesses. Individual genomes consisted of 50 genes. Mutations occurred at a rate of 0.005, 0.01 or 0.02 per gene per generation. The mean and maximum fitness of mutations could be varied, as could the proportion of beneficial mutations. The carriers of the koinophilic trait avoided, with adjustable degrees of intensity, mates displaying unusual phenotypic features (traits with population frequencies < 0.5); panmictic individuals mated randomly. The results show that koinophilia tends to replace panmixis whenever the preference for common phenotypic traits is strongly expressed, when few mutations are beneficial (1% instead of 10%), or when the maximum fitness of mutations is low (1.2 instead of 2.0). The mutation rate and mean fitness of mutations had only minor effects on the relative advantage of koinophilia. PMID- 7869735 TI - Promoter strength prediction based on occurrence frequencies of consensus patterns. AB - A training sample of 14 sequences of E. coli, each 70 or 69 base pairs long, with their (relative) promoter strengths given by Deuschle et al. (1986, EMBO J. 5, 2987-2994), is used to find a relation between the occurrence frequencies of the two consensus patterns and the promoter strength. The approach is restricted to an analysis of purine and pyrimidine organization using the theory of stationary alternate Markov chains of first order. Further, it is shown, both empirically by regression analysis, and by a Markov-chain-oriented statistical analysis, that the difference of occurrence frequencies and the determinant of transition matrix, which was introduced in a previous paper (Recknagel et al., 1993, J. theor. Biol. 162, 75-80), are equivalent measures with respect to the task of promoter strength prediction. An empirical regression equation is given that allows the promoter strength to be forecast from the occurrence frequencies of the canonical hexamers in the consensus boxes. Three E. coli promoters of an examination sample, separated from the training sample, are classified this way, in agreement with the experimental findings. PMID- 7869736 TI - Defective escape mutants of HIV. AB - The virological literature presents two broad types of defective virus mutants that can alter the outcome of viral infection. In some infections, defective interfering particles reduce the replication of wild-type virus and lead to an attenuated or persistent infection. In other cases, very specific and highly pathogenic defective mutants lead to virulent disease in the presence of a much less pathogenic but replication-competent helper virus. Here, we outline the theoretical possibility that defective mutants of HIV, which escape from some of the immune responses directed at the wild-type virus, can have a positive effect on total virus growth in HIV infections. The high error rate of HIV may generate many mutants that have some altered epitope (escape mutants), but at the cost of greatly reduced or completely impaired reproductive abilities. If these mutants retain some ability to impair immune cell function, then the production of such "defective escape" mutants may enhance overall virus reproduction. This will be illustrated by a mathematical model. PMID- 7869737 TI - Species selection on organismal integration. AB - Selection processes of entities higher than individuals have recently been suggested to play a potential role in macroevolution. In particular, population level traits such as variability seem likely candidates for higher-level selection processes because they interact with population fitness (survival). In this paper, I expand on that theme and argue that a population level trait, such as organismal integration, measured by the genetic variance-covariance matrix, can be subject to interpopulational selection. This is so because a population consisting of individuals with a high degree of integration will respond faster to selection than a less integrated one, and thus more rapidly reach new optima. This idea generates a number of predictions which are supported by data from natural and laboratory populations of a diverse array of organisms. First, the level of genetic integration in morphological characters is generally quite high. Second, there are a number of cases where the within- and among-population correlation matrices are similarly oriented. Third, the main pattern of morphological variation in birds is that species within genera are most exclusively oriented along a size-axis. These results are consistent with the ideas put forward in this paper, though not providing conclusive evidence. PMID- 7869738 TI - Childhood cancers and competing causes of death. AB - From the survey that first identified cancer effects of foetal irradiation and related sources has come support for the following hypotheses: (1) competing causes of death for childhood cancers include abortions (solid tumours) and infections (RES neoplasms); (2) the forms taken by RES neoplasms vary with the nature and intensity of indigenous infections; (3) ideal conditions for developing diffuse RES neoplasms (leukaemia) include the gross immunological incompetence caused by trisomy 21; (4) the unusually localised RES neoplasms found in children who have survived repeated attacks of malaria (Burkitt lymphoma and chloroma) are probably the result of these children having exceptionally high levels of passive as well as active immunity; and (5) when teratogenic effects of in utero mutations include faulty erythropoiesis as well as faulty leucopoiesis, infections are not the only rival causes of death. PMID- 7869739 TI - Viable bone marrow stromal cells are required for the in vitro survival of B-cell precursor acute lymphoblastic leukemic cells. AB - The growth of B-cell precursor acute lymphoblastic leukemic (BCP ALL) cells in vitro is dependent on interactions with bone marrow (BM) stromal cells. We have recently demonstrated that the rate of cell division of BCP ALL cells increases when cultured in direct contact with BM stromal cells. A number of studies have examined the binding of BCP ALL cells to BM stromal cells and extracellular matrix components. To date there have been no studies examining the effect of such binding on the growth and survival of BCP ALL cells. In this study, by measuring the growth parameters of these cells with use of a lipophilic fluorescent probe, PKH 26 GL, we demonstrate the positive effect of viable BM stromal cells on BCP ALL cell survival in 10 patient samples. At the same time, by comparing these cultures with cultures of the same patient samples in the presence of glutaraldehyde-fixed stromal cells, deoxycholic acid-derived stromal cell matrices, purified laminin, collagen or fibronectin, the role of various stromal cell-derived contact components in BCP ALL survival was tested. It was shown that the survival of BCP ALL cells in vitro was dependent upon viable BM stromal cells present in co-culture as the various contact components did not show any functional effect on BCP ALL cell survival. PMID- 7869740 TI - Morphological comparison of dysplastic changes between de novo acute myeloid leukemia (AML) with trilineage myelodysplasia and AML developed from de novo myelodysplastic syndromes. AB - To elucidate the clinical and morphological differences between de novo acute myeloid leukemia (AML) with trilineage myelodysplasia (AML/TMDS) and AML developed from de novo myelodysplastic syndrome (MDS), we analyzed 12 and 13 cases, respectively. The median age of AML/TMDS patients was lower, but not significantly so, than the median age of patients with AML from MDS (45 vs 55 years). Platelet counts and the percentage of peripheral blasts were significantly higher in the patients with AML/TMDS than in the patients with AML from MDS (p < 0.05 and p < 0.01, respectively). Four patients with AML from MDS could not be classified into FAB subtypes. Eight patients (67%) with AML/TMDS achieved complete remission (CR). Nine with AML from MDS were treated with less intensive regimens; none of these patients achieved CR. In the comparison of dysplastic changes in both groups, the rate of pseudo-Pelger anomaly was significantly higher in the patients with AML from MDS (p < 0.001), and micromegakaryocytes and multinuclear erythroblasts were also more frequent in the patients with AML from MDS than in those with AML/TMDS (p < 0.05). The overall survival curves showed that the 12 patients with TMDS had a significantly better survival than the 13 patients with AML from MDS (p < 0.01). Our findings suggest that AML/TMDS is a subtype of de novo AML and is different from AML from MDS. Further study is required to determine the biological differences between AML with TMDS and AML transformed from MDS. PMID- 7869741 TI - Occupational and environmental exposures and myelodysplasia: a case-control study. AB - A case-control study of newly diagnosed myelodysplastic syndrome patients investigated lifetime exposures through occupation, environment or hobby by questionnaire, structured and semi-structured interview. The exposure histories of 400 individually matched pairs were compared. Increased or possibly increased odds ratios were observed for radiation (2.05, 95% confidence interval 1.16 3.76), halogenated organics (1.57, 0.97-2.57), metals (1.40, 0.99-2.00), several specific radiation exposures and individual chemicals and for childlessness (1.46, 1.01-2.11). Since myelodysplasia generally carries a poor prognosis, whether or not individuals convert to leukaemia or to other cancer, these findings add to previous reports of exposures implicated in the aetiology of leukaemia and add to the case for minimizing exposures to radiation and halogenated organics. PMID- 7869742 TI - Cytarabine-induced pericarditis: a case report and review of the literature of the cardio-pulmonary complications of cytarabine therapy. AB - Pericarditis is a rare complication of chemotherapy. This report describes a patient who developed symptoms, signs, and electrocardiographic evidence of pericarditis following treatment with high dose cytarabine. The patient had no clinical or echocardiographic evidence of infection or leukemic involvement of the pericardium. Isolated pericarditis associated with high dose cytarabine has been rarely reported. This therapy is frequently used and, therefore, it seems prudent to alert physicians to this potential complication of cytarabine. The cardiopulmonary complications of cytarabine are also reviewed. PMID- 7869743 TI - Early identification of M2 AML with the (8;21) translocation plus myelodysplastic features. PMID- 7869744 TI - Bone marrow-derived T-cell clones obtained from untreated acute myelocytic leukemia exhibit blast directed autologous cytotoxicity. AB - The eradication of minimal residual blast populations by activation of autologous cytotoxic cells with interleukin 2 (IL-2) is a new promising tool in the treatment of acute myelocytic leukemia (AML). However, the immunological effector cells are not yet clearly defined. The present study was designed to investigate the presence of cytotoxic precursor cells in active AML and to identify phenotypical and functional characteristics of autologous anti-leukemic cytotoxic effector cells. For this purpose, mononuclear cells (MNC) containing at least 70% leukemic blasts were isolated from bone marrow of untreated AML and cultured in the presence of 3000 IU/ml recombinant IL-2 (rIL-2) for 6-8 weeks. Under these conditions, T-cells were selected in the bone marrow cultures and overgrew the leukemic blasts. The resulting T-cell populations were cloned by limiting dilution and the clones obtained were characterized for their phenotypical and functional patterns. Totally, cloning resulted in 68 clones and a few cell lines. The clonality was verified by RT PCR analysis of TCR V beta gene expression. All clones obtained stained positive for CD2, CD3, DR and CD56. The vast majority (68%) of T-cell clones/lines was CD4+, a few clones expressed CD8 (19%) or CD4 and CD8, and four clones were of TCR gamma delta origin. Seven of 15 clones tested, including three CD4+, two CD8+ and two TCR gamma delta(+)-clones were found to be cytotoxic against autologous leukemic blast cells. All except one clone expressed oncolytic activities against allogeneic blasts too. One of the TCR gamma delta(+)-clones demonstrated NK activity by lysis of K562 targets. The majority of the T-cell-clones released IL-2, IL-8, TNF-alpha, GM-CSF but only a few IFN gamma and expressed high levels of mRNA for IL-2, TGF-beta and IL-10. None of the clones was found to produce IL-3, IL-4, IL-7 and TNF-beta. The data provide evidence of the existence of T-cell precursors in untreated AML bone marrow differentiating to cytotoxic cells with activity against autologous and allogeneic AML blast cells. PMID- 7869745 TI - Induction of leukemia in mice using a radiation leukemia virus-induced cell line: a model system for studying oncogenic progression. AB - Leukemogenesis induced by slowly transforming retroviruses is a multistep process which is difficult to dissect because of its long latency and the problem of distinguishing oncogenic from differentiative events. A method for leukemia induction in mice has been developed using a cell line isolated following in vitro infection with the slowly transforming murine radiation leukemia virus (RadLV). The CI-V13D cell line represents a lymphoid precursor cell type at an early stage in cell transformation and can develop subcutaneous tumors in irradiated syngeneic hosts but not in allogeneic mice even after sublethal irradiation. Selective growth in allogeneic (CBA/H) mouse thymus has been demonstrated, but this requires preirradiation of the recipient. Upon reisolation from CBA/H thymus, C1-V13D progeny clones displayed increased tumorigenic potential in comparison to the 'parental' CI-V13D cell line. Tumorigenicity was shown to increase with serial passage through thymus and electron micrographs of clones also revealed increased production of C-type retroviruses. This new model for oncogenic progression should be more amenable to analysis of early genetic changes occurring during replication of leukemia in the thymus. PMID- 7869746 TI - Effects of erythropoietin, IL-3, IL-6 and LIF on a murine megakaryoblastic cell line: growth enhancement and expression of receptor mRNAs. AB - We examined the effects of recombinant human erythropoietin (rhEPO), recombinant murine interleukin 3 (rmIL-3), recombinant human interleukin 6 (rhIL-6), recombinant human interleukin 11 (rhIL-11), recombinant murine leukemia inhibitory factor (rmLIF) and recombinant murine granulocyte-macrophage colony stimulating factor (rmGM-CSF) on the growth of murine megakaryocytic cell lines. In serum-free methylcellulose culture supplemented with bovine serum albumin (BSA), the addition of rhEPO (0.1-10 U/ml), rmIL-3 (10-500 U/ml), rhIL-6 (100 10,000 U/ml), rmLIF (100-10,000 U/ml), or rmGM-CSF (10-1000 U/ml) enhanced colony growth in L8057Y5 cells, which had been maintained in protein-free culture, mostly in a dose-dependent fashion; rhIL-11 did not have any stimulatory effect at the tested doses (10-1000 U/ml). In addition, colony growth of L8057 cells, which had been maintained in serum-containing culture, was enhanced, but to a lesser extent, by the addition of these cytokines except rhEPO (the cultures were supplemented with 1% fetal bovine serum. Among the cytokines that showed growth enhancing effects on L8057 cells, the expression of mRNAs encoding receptors for EPO, IL-6 and IL-3 was examined by northern blot analysis or reverse transcription polymerase chain reaction (RT-PCR). In both cell lines, mRNAs for EPO-R, IL-6R, gp130, IL-3R alpha and beta chains were constitutively expressed. The results suggest that L8057 and L8057Y5 cell lines have characteristics of megakaryoblastic cells in their biological responses to cytokines, as well as in the expression of cytokine receptor mRNAs, and that the growth-enhancing effects of these cytokines on the cell lines may be achieved through specific receptors. Our findings show the value of these cell lines for investigating the mechanisms of growth signal transduction in megakaryopoiesis. PMID- 7869747 TI - Advanced image analysis systems in cell, molecular and neurobiology applications. AB - Many of today's image acquisition devices (scanners and cameras) yield high resolution (1280 x 1024 pixels is typical) and/or high-precision (> 8 bits) image data. When coupled to a powerful image analyzer these image acquisition devices offer practical advantages in many bioscience applications. The benefits of high resolution include better contrast transfer (sharper images with more accurate density rendition) and an ability to work with large specimens at lower optical magnifications (larger field of view). High precision is useful if images contain subtle features (e.g., fluorescently labeled processes at densities close to background) and/or wide dynamic range. Examples are given, illustrating the use of a number of medium- and high-performance image acquisition devices with an advanced image analyzer. The examples include a comparison of intensified and integrating cameras in fluorescence microscopy, evaluation of the performance of a fast, cooled integrating camera in ratio fluorescence imaging, and a comparison of film and storage phosphor-plate performance in quantitative receptor autoradiography. PMID- 7869748 TI - Anatomical and functional imaging of neurons using 2-photon laser scanning microscopy. AB - Light scattering by brain tissue and phototoxicity are major obstacles to the use of high-resolution optical imaging and photo-activation ('uncaging') of bioactive compounds from inactive ('caged') precursors in intact and semi-intact nervous systems. Optical methods based on 2-photon excitation promise to reduce these obstacles (Denk, 1994; Denk et al., 1990, 1994). Here we show a range of imaging modes based on 2-photon laser scanning microscopy (TPLSM) as applicable to problems in neuroscience. Fluorescence images were taken of neurons labeled with ion-sensitive and voltage-sensitive dyes in invertebrate ganglia, mammalian brain slices, and from the intact mammalian brain. Scanning photochemical images with whole-cell current detection (Denk, 1994) show how the distribution of neurotransmitter receptors on the surface of specific cells can be mapped. All images show strong optical sectioning and usable images can be obtained at depths greater than 100 microns below the surface of the preparation. PMID- 7869749 TI - Combining patch-clamp and optical methods in brain slices. AB - Combining patch-clamp and optical imaging techniques in brain slices offers several advantages for physiological studies of nerve cells. Numerous practical considerations weigh heavily in this design of an apparatus suitable for such combined measurements. These considerations include the thickness of the slices, the type of microscope to be used for imaging and the kind of optical signal to be measured. A system that combine optical and patch-clamp methods can be modified readily to permit studies of intracellular and extracellular signaling pathways via flash photolysis of caged compounds. PMID- 7869750 TI - Functional magnetic resonance imaging (FMRI) of the human brain. AB - Functional magnetic resonance imaging (FMRI) can provide detailed images of human brain that reflect localized changes in cerebral blood flow and oxygenation induced by sensory, motor, or cognitive tasks. This review presents methods for gradient-recalled echo-planar functional magnetic resonance imaging (FMRI). Also included is a discussion of the hypothesized basis of FMRI, imaging hardware, a unique visual stimulation apparatus, image post-processing and statistical analysis. Retinotopic mapping of striate and extrastriate visual cortex is discussed as an example application. The described echo-planar technique permitted acquisition of an image in 40 ms with a repetition rate of up to 2 per second. However, FMRI responses are slow compared to changes in neural activity. Onset of a visual checkerboard test pattern evoked a response that was delayed by 1-2 s and reached 90% of peak in 5 s. Return to baseline following stimulation was slightly slower. Alternating control (blank) and test (checkerboard) patterns every 20 s induced a cyclic response that was detected in the presence of noise using a cross-correlation technique that was verified by parametric statistics. FMRI revealed retinotopically organized patterns of visually evoked activity in response to annular stimuli that increased in visual field eccentricity. Retinotopy was also observed with test patterns rotated around the fixation point (center of gaze). Results from repeated tests 1 week apart were highly similar. Compared to passive viewing, an active visual discrimination task enhanced responses from extrastriate association cortex. PMID- 7869751 TI - Imaging neuronal development with magnetic resonance imaging (NMR) microscopy. AB - An ideal technique for following the development of the vertebrate nervous system would allow cells to be followed at the resolution of light microscopy at depths of several millimeters into the tissue. This would permit critical events to be followed at cellular or sub-cellular resolution even deep within the developing organism. To date, no technique has emerged with all of the needed properties. Light microscopy can follow a cell and its descendants after they have been labeled by either the infection of embryonic cells with a recombinant retrovirus or the microinjection of individual precursor cells with enzymes or fluorescent dyes. However, light microscopy cannot image events deeper than a few hundred micrometers within an embryo due to light scattering and aberrations in the objective lenses and other optics. Magnetic resonance imaging (MRI) does not suffer from these limitations, routinely being used to image in 3 dimensions through specimens as large as adult humans. However, it is relatively slow and, as implemented to date, it cannot routinely achieve cellular resolution. Here, we present our attempts to meet the technical challenges posed by in vivo MRI microscopy. As an example of both the progress and the future challenges, we present images of cells within the developing frog embryo over a several day time course. PMID- 7869752 TI - Quantification of real-time confocal images of the human cornea. AB - Real-time confocal microscopy was used to obtain images of the surface cells of the cornea in vivo in human subjects and in non-human primates. The surface cells represent the barrier between the tear layer and the internal cellular environment and as such, the state of these cells is indicative of the health of the cornea. In our study, confocal microscopy of the surface cells revealed prominent, centrally located nuclei. With the use of a series of image analysis procedures, the nuclei were located automatically and distances to the nearest neighbors were determined. Comparison of these procedures in 8 human corneas and 1 non-human primate cornea showed that unaided computer analysis of the surface cells was as accurate as manual location of the cell nuclei. The distribution of nearest-neighbor distances was found to be best fitted by a gamma distribution. Simulation of a condition marked by loss of surface cells demonstrated that the alpha (shape) and beta (scale) parameters could be used to compare the distribution of nearest-neighbor distances. Thus, confocal microscopy coupled with these image analysis and statistical procedures could provide an objective, quantitative approach to monitoring the epithelial barrier under clinical and experimental conditions, for example during post-surgical or post-traumatic healing or in the evaluation of the efficacy of topical therapeutic agents. PMID- 7869753 TI - Scanning laser photostimulation: a new approach for analyzing brain circuits. AB - A new technique for understanding the organization of complex circuits in the vertebrate brain, scanning laser photostimulation, is described. This approach is based on the photolysis of a caged form of the excitatory neurotransmitter glutamate. Computer-controlled photostimulation and whole cell recording in brain slices allow the construction of detailed maps of the position, strength, sign and number of inputs converging on a single postsynaptic neuron. Scanning laser photostimulation offers many advantages over current techniques: spatial resolution is superb, fibers of passage are not activated, and thousands of presynaptic locations can be stimulated. This review describes the technique of photostimulation, outlines the instrumentation, necessary to implement it, and discusses the interpretation of photostimulation-derived data. Several examples of applications, ranging from mapping circuits in the mammalian visual cortex to determining receptor distributions on single neurons are considered. Although still in its early stages, scanning laser photostimulation offers neuroscientists a powerful tool for determining the organization and function of local brain circuits. PMID- 7869754 TI - Quantitative image analysis for immunocytochemistry and in situ hybridization. AB - Image analysis hardware, software, and procedures are described for analysis of tissue reacted for antibody immunocytochemistry and in situ hybridization. A Magiscan image analyzer is used to process images viewed with a light microscope. LUT functions, spatial filters (parabola) and gray level convolutions (sharpen, laplacian, mexican hat) are applied in order to extract immunoreaction product or autoradiographic grains. These objects are then thresholded and binary operators (erosion, dilation, separation) are applied to separate closely apposed objects. Measurements routines are used to estimate the optical density and size of labeled profiles or to count grains and compute grain density per profile. A JEOL 1210 electron microscope is used to view tissue treated for post-embedding immunochemistry. Digital images are captured with a Kodak 1K CCD camera, archived, transported across a local area network, stored on optical disks and analyzed on a MacIntosh IIci. NIH Image is used to process these images. Results show that the optical density of GABA antibody labeling is reduced by monocular deprivation, that substance P mRNA hybridization labeling is increased by scopolamine, and that retinal terminals are densely labeled by antibodies to glutamate. These techniques are thus useful for measuring the amount of change in labeling after experimental manipulations and for distinguishing labeled from unlabeled profiles. PMID- 7869755 TI - Postmortem anatomy from cryosectioned whole human brain. AB - A system of histologic and digital processing protocols are presented for the acquisition of high-resolution digital imagery from postmortem cryosectioned whole human brain and head for computer-based 3-dimensional (3D) representation and visualization. We designed and evaluated several protocols for optimal preparation of frozen specimens including fixation, decalcification, cryoprotection, freezing and sectioning procedures. High-resolution (1024(2) pixel) serial images were captured directly from the cryoplaned blockface using an integrated color digital camera and fiber optic illumination system mounted over a modified cryomacrotome. Specimens frozen and sectioned with the cranium intact preserved brain spatial relationships and anatomic bony landmarks. Color preservation was superior in unfixed tissue heads were incompatible with decalcification and cryoprotection procedures and section collection from such specimens was complicated by bone fragmentation. Collection of 1024(2) images from whole brain resulted in a spatial resolution of 200 microns/pixel in a 1-3 Gbyte data space. Even higher 3D spatial resolution was possible by primary image capture of selected regions such as hippocampus or brain stem. Discrete registration errors were corrected using image processing strategies such as cross-correlative and other algorithmic approaches. Data sets were amenable to resampling in multiple planes as well as scaling and transpositioning into standard coordinate systems. These methods enable quantitative measurements for comparison between subjects and to published atlas data. These techniques allow visualization and measurement at resolutions far higher than those available through other imaging technologies and provide greatly enhanced contrast for delineation of neuroanatomic structures, pathways, and subregions. PMID- 7869756 TI - A digital brain atlas and its application to the visceral neuraxis. AB - We describe the details and application of a digital brain atlas for the comparison and integration of graphical neurobiological data. The atlas consists of multiple sets of high-resolution video images acquired from histological tissue sections representing a 3-dimensional (3D) volume of an exemplar rat brain. Through an interactive graphical interface running on a standard computer workstation, experimental data is brought into register with the atlas. Once in the atlas, coordinate reference frame data can be compared, analyzed, and visualized in 3 dimensions. We demonstrate the validity and usefulness of the digital brain atlas with a series of results on the visceral neuraxis in the rat. PMID- 7869757 TI - Neurotechnology: expanding opportunities for funding at the National Institute of Mental Health. AB - The National Institute of Mental Health recognizes the importance that creative development of technology and methodology play in brain and behavioral science research. This institute is making major efforts to support such development through specific initiatives, like the Human Brain Project. In addition, this Institute is actively building bridges between business and academic research communities to make optical use of funds for the research and development of commercially viable technologies relevant to all aspects of the Institute's mission through the Small Business Innovation Research and Small Business Technology Transfer Programs. Together, these efforts will culminate in a more vigorous scientific enterprise, and ultimately benefit the entire mental health community and society. PMID- 7869758 TI - Short-term treatment for adult hypergranular and microgranular acute promyelocytic leukemia. AB - A high hemorrhagic risk and a complete response to the differentiative agent all trans-retinoic acid (ATRA) are the main clinical features of acute promyelocytic leukemia (APL), two distinct subtypes of which have been recognized, the common hypergranular leukopenic form (M3) and a microgranular hyperleukocytic variant (M3v). We analyzed, with emphasis on both disease- and therapy-related prognostic factors, the results from a 9-year trial in 65 adults with M3 and M3v APL, treated homogenously with a short-term therapy (STT) program excluding maintenance. STT comprised a maximum of six courses with doxorubicin, cytosine arabinoside (ara-C), and 6-thioguanine. Sixty-five APL patients formed the study group, M3v accounting for 25% of cases. In M3v, the absolute blast cell count was significantly higher (p < 0.0001) and early hemorrhagic deaths were more frequent (p = 0.05). The blast count correlated inversely with the probability of remission (p = 0.005), poor-risk patients being those with > 10 x 10(9)/l blast cells. During the study, the median survival improved from 0.1 to 2.7 years (p = < 0.005). In first place, response to chemotherapy increased from 42 to 84% (p = 0.006), by giving daily prophylactic platelet transfusions (to > 30 x 10(9)/l) and no heparin (course I), and by avoiding too toxic high-dose ara-C and deferring treatment in infected/neutropenic patients showing the atypical differentiative bone marrow pattern (course II). Secondly, the probability of first unmaintained remission differed significantly between patients given intentionally more than four total chemotherapy courses or intermediate/high-dose ara-C consolidation (0.59 at 5 years) and those treated less intensively (0.21) (p < 0.005). Intensive STT was very effective for the management of adult APL patients at standard hemorrhagic risk and receiving optimal supportive care. In high-risk patients with hyperleukocytosis and M3v, induction results could be improved by the concomitant use of ATRA. M3v in adults must be recognized promptly because of the very high early hemorrhagic risk. PMID- 7869759 TI - Sequential targeted therapy for relapsed acute promyelocytic leukemia with all trans retinoic acid and anti-CD33 monoclonal antibody M195. AB - Acute promyelocytic leukemia (APL) provides a model to examine the sequential use of selective oncogene product-targeted and lineage-targeted agents. All-trans retinoic acid (RA) has been shown to produce brief remissions by a novel differentiating mechanism in most patients with APL. M195, a mouse monoclonal antibody (moAb) reactive with the cell-surface antigen CD33, can target myeloid leukemia cells in patients and reduce large leukemic burdens when labeled with 131I. We studied whether 131I-M195 could safely reduce minimal residual disease and prolong remission and survival durations in patients with relapsed APL after they had attained remission with all-trans RA. Seven patients with relapsed APL in second remission were treated with either 70 (n = 2) or 50 (n = 5) mCi/m2 of 131I-M195. As a measure of minimal residual disease, we serially monitored PML/RAR-alpha mRNA by a reverse transcription polymerase chain reaction (RT-PCR) assay. There was no immediate toxicity. Late toxicity was limited to myelosuppression, but no episodes of febrile neutropenia were seen. Six patients had detectable PML/RAR-alpha mRNA after all-trans RA therapy; two had single negative RT-PCR determinations following 131I-M195. Median disease-free survival of the seven patients was 8 months (range 3-14.5). Four patients with median follow-up of 24 months remain alive, and median overall survival exceeds 21+ months (range 5.5-33+). This regimen based on targeted therapy compares favorably to other approaches for the treatment of relapsed APL, including that used in the immediately preceding trial in which patients were induced into remission and maintained with all-trans RA, as well as other chemotherapy-based regimens. These data support further study of moAb-based therapy for minimal residual disease in acute leukemia. PMID- 7869760 TI - Identification of a favorable subgroup of patients with generalized immunocytomas by follicular dendritic cells. AB - In the present study, 89 patients with generalized immunocytoma were analyzed retrospectively for the prognostic influence of clinical features and of immunophenotype using bone marrow biopsies. Univariate analysis selected the following variables as significant for survival: age over 60 years (p = 0.021), Rai and Binet stage (p = 0.008 and 0.004, respectively), presence or absence of follicular dendritic cells (FDC, p = 0.036), presence or absence of anemia (p = 0.037). Multivariate regression analysis showed independent prognostic significance of age (p = 0.001), Rai stage (p = 0.003), and the presence of follicular dendritic cells (p = 0.010). Comparing CD5 positive and CD5 negative immunocytomas, no survival advantage for one of the two groups was seen. Presence of follicular dendritic cells clearly identified a favorable prognostic subgroup: of the 89 patients presented, only three of 18 (16.6%) with detectable FDC in bone marrow died within the observation period, as compared to 34 of 71 (52.1%) patients without FDC. Multivariate analysis emphasized the independent prognostic value of the presence of FDC. The high predictive capacity of follicular dendritic cells could add useful information to the commonly used Rai and Binet staging systems for immunocytoma. PMID- 7869761 TI - Acute leukemia coexpressing myeloid, B- and T-lineage associated markers: multiparameter analysis of criteria defining lineage commitment and maturational stage in a case of undifferentiated leukemia. AB - Coexpression of myeloid, B-, and T-lineage associated markers was found in a patient with morphologically and cytochemically undifferentiated acute leukemia. Surface marker analysis using two-color immunofluorescence staining characterized blast cells to express CD34, CD38, CD117, and class II antigens, coexpressing TdT, CD4, CD7, CD13, CD19, and CD33. Cytoplasmic expression of myeloperoxidase, CD3, and CD22 could not be demonstrated. Monosomy for chromosome 7 was found by cytogenetic analysis. The absence of clonal rearrangements of immunoglobulin or T cell receptor genes was shown by Southern blot analysis. Using a 3H-thymidine incorporation assay, DNA synthesis of leukemic blasts could be stimulated by IL 3, IL-6 and G-CSF in vitro. The present case did not offer specific criteria of lineage commitment. Corresponding to an equivalent counterpart in normal hematopoiesis, the involved cell population may reflect an early, most immature developmental stage within a multipotent progenitor cell compartment. PMID- 7869763 TI - Endogenous megakaryocyte and erythroid colony formation from blood in essential thrombocythaemia. AB - The in vitro cultures of haematopoietic progenitors have been reported to be useful in the diagnosis of myeloproliferative disorders since the so-called endogenous erythroid and megakaryocyte colony formation has, in most studies, been found in these diseases. In order to know their value as diagnostic criteria in essential thrombocythaemia (ET) we have studied megakaryocyte (with and without phytohaemagglutinin-stimulated leucocyte conditioned medium) and erythroid (with and without erythropoietin) colony formation in vitro by progenitors from blood in 60 patients with ET and in ten with reactive thrombocytosis (RT) using the methyl-cellulose assay. Out of 60 ET patients endogenous megakaryocyte colony growth was observed in 38 (63%) and endogenous erythroid growth in 42 (70%). None of the patients with RT or any of the controls showed either type of endogenous growth. Fifty-five (91%) of the patients with ET showed megakaryocyte and/or erythroid endogenous colony formation whereas five (9%) did not have any kind of endogenous colonies, although cultures were performed sequentially. In conclusion, a positive endogenous megakaryocyte and/or erythroid colony growth from blood is a frequent and characteristic finding in ET patients and should be used as a useful marker in this disease. PMID- 7869762 TI - Continuing immunoglobulin heavy chain gene rearrangements in chronic myeloid leukemia with recurrent B-lymphoid blast crises after bone marrow transplantation. AB - We sequentially analyzed the immunoglobulin heavy chain variable (IgH V) region gene of leukemia cells obtained from a chronic myeloid leukemia (CML) patient who had three episodes of B-lymphoid crisis after bone marrow transplantation. Southern blot analysis using the JH probe showed different rearranged bands at each crisis, although the same rearranged bands of the BCR gene were observed. We amplified and sequenced the IgH V region gene of the leukemia cells by reverse transcriptase polymerase chain reaction (RT-PCR) using the primers corresponding to the consensus 5'VH and mu constant regions. The dominant leukemia clone at each crisis had a unique VH-D-JH rearrangement; VH4A (V79)-DLR2-J5 (clone-1), VH4B (DP70)-DK4-J6 (clone-2) and VH4A (V79)-DN4-J6 (clone-3) at the first, second and third crises, respectively. Further analysis by PCR amplification using the consensus 5'VH and clone-specific primers revealed that clone-1 underwent VH4- >VH3 replacement at the second crisis, and that clone-3 was already in existence at the first crisis. Moreover, the DN4-J6 joining clone, in which the sequence was the same as that of clone-3, was identified at the first and third crises by PCR amplification using primers corresponding to the region upstream of the DN4 segment and DN4-J6 boundary of clone-3. These observations suggest that multiple clones were generated from the progenitor cells of blast crisis, which were transformed at a very early stage of B-lymphocyte ontogeny, by continuing rearrangement mechanisms of the IgH genes, and that the dominant clone at each crisis was undergoing change. PMID- 7869764 TI - Der(16)t(1;16)(q10;p10) in multiple myeloma: a new non-random abnormality that is frequently associated with Burkitt's-type translocations. AB - Aneuploidy is a frequent feature in multiple myeloma. Cytogenetic analyses have shown that a 14q+ chromosome resulting from either a t(8;14)(q24;q32) or a t(11;14)(q13;q32) was the most consistent abnormality but no specific chromosomal aberration has been identified in this disease. Bone marrow cells from 121 consecutive patients with multiple myeloma were analyzed cytogenetically by standard banding techniques including RHG, GTG and CBG banding. Cells were cultured for 24-96 h in the presence or in the absence of interleukin-6. Clonal abnormalities were detected in 41 of the 121 patients (34%). A der(16)t(1;16)(q10;p10) abnormality was identified in nine of these 41 patients (22%). Der(16) was identified at diagnosis in five patients, during disease progression in two additional patients, and at the time of a relapse in the two last cases. The t(1;15)(q10;p10) translocation was always unbalanced, resulting in a monosomy 16q in all cases. The CBG banding did not demonstrate dicentric chromosomes and the whole chromosome painting confirmed the der(16). A large number of other chromosomal abnormalities were associated with der(16), including chromosomal rearrangements involving the 8q24 band in five cases. Four of these five cases were Burkitt's-type translocations. This observation suggests that der(16)t(1;16)(q10;p10) could be one of the most frequent chromosomal abnormalities that can be identified in multiple myeloma cells. PMID- 7869765 TI - Identical fusion transcript associated with different breakpoints in the AML1 gene in simple and variant t(8;21) acute myeloid leukemia. AB - Fluorescence in situ hybridization (FISH) and/or RNA-based polymerase chain reaction (RT-PCR) were used to analyze the breakpoints within the AML1 gene and the AML1 fusion transcripts in t(8;21) acute myeloid leukemia (AML). Twenty-two patients presented with the simple t(8;21)(q22;q22) and one with a complex variant t(8;2;16;21). In eight cases we used FISH with AML1 cosmid probes on metaphase chromosomes as well as RT-PCR to detect the junctions of MAL1/CDR (ETO,MTG8). Five cases were analyzed by FISH alone and ten cases by RT-PCR alone. By FISH we could identify three groups according to the distribution of the fluorescent signal. Signals were found in group 1 on chromosomes 21 and 21q+, in group 2 on chromosomes 21, 21q+ and 8q- and in group 3 on chromosomes 21 and 8q-. In all groups we could detect an identical AML1/CDR fusion transcript. This transcript showed splicing of AML1 exon 5 onto CDR. Thus regardless of the heterogeneity suggested by FISH, all the breakpoints in the AML1 gene were clustered in the same intro between exons 5 and 6. Our results bring to over one hundred the number of t(8;21) cases in which an identical translocation could be detected at molecular level by RT-PCR. The high sensitivity of the technique makes it suitable for the diagnosis of this translocation in different stages of the disease. The impact of the molecular detection of t(8;21) cells in clinical remission as far as the treatment and the management of the disease are concerned deserves further discussion. PMID- 7869767 TI - The SH2 domain of ABL is not required for factor-independent growth induced by BCR-ABL in a murine myeloid cell line. AB - Chronic myelogenous leukemia (CML) is characterized by the presence of a specific chromosomal translocation between the long arms of chromosomes 9 and 22 that results in the fusion of BCR encoded sequences upstream of exon 2 of c-ABL. This fusion gene produces a 210-kDa chimeric BCR-ABL protein that has elevated tyrosine kinase activity. Several substrates of this activated tyrosine kinase have been reported. However, their necessity for the transforming functions of BCR-ABL has not been determined. A specific deletion of the SH2 domain of ABL was created to determine whether this mutation would alter the ability of BCR-ABL to induce factor-independent growth of a murine myeloid cell line and to determine whether the SH2 domain mediates the interaction of BCR-ABL with any of its substates. Our results indicate that the SH2 domain of BCR-ABL is not required for the induction of growth factor independence and is not required for the association of BCR-ABL with rasGAP or SHC. However, myeloid cells expressing this mutant lack the tyrosine phosphorylation of a 62-kDa rasGAP associated protein. PMID- 7869766 TI - Interleukin (IL)-6 signaling leads to phosphorylation of the small heat shock protein (Hsp)27 through activation of the MAP kinase and MAPKAP kinase 2 pathway in monocytes and monocytic leukemia cells. AB - Interleukin-6 is a multifunctional cytokine which regulates various aspects of the host immune response. Here we show that signaling events transferred by IL-6 in monocytes and the U937 human monocytic leukemia cell line lead to the phosphorylation of the small heat shock protein (Hsp)27. Phosphorylation of Hsp27 is both dose- and time-dependent. In the absence of NaF, a serine/threonine phosphatase inhibitor, IL-6 failed to initiate Hsp27 phosphorylation in vitro. IL 6 also failed to phosphorylate Hsp27 when cells had been deactivated with tyrosine kinase inhibitors such as genistein. The capacity of cellular extracts to phosphorylate Hsp27 could be, however, restored when either immunoprecipitated activated MAP kinase or purified MAPKAP kinase 2 was added to cell lysates. These findings suggest that IL-6-mediated phosphorylation of Hsp27 results from activation of MAPKAP kinase 2, a serine/threonine kinase which is activated by MAP kinase. Taking together, our findings indicate that IL-6-induced activation of MAP kinase by IL-6 entails the activation of MAPKAP kinase 2 and subsequent phosphorylation of the Hsp27. PMID- 7869768 TI - Effect of retinoic acid isomers on proliferation, differentiation and PML relocalization in the APL cell line NB4. AB - Retinoic acids exert a wide physiological role in development and differentiation. Retinoic acids have also been used in the treatment of human cancers, particularly in acute promyelocytic leukemia (APL). A structure-function relationship of the RA isomers in terms of clinical effect has been observed since all-trans retinoic acid (ATRA) induces a high complete remission rate while 13-cis retinoic acid (13-cis RA) shows much poorer effect. In this study, we examined the effect of RA isomers, including ATRA, 13-cis RA and 9-cis RA, on the proliferation and differentiation of NB4 cells. A number of parameters such as cell growth curve, dynamics of cell cycle, expression of clusters of differentiation and reduction of nitro blue tetrazolium (NBT) as well as immunofluorescence staining of PML were used to evaluate the effects of three isomers at two concentrations (10(-8) M and 10(-7) M). It has been shown that during the first 48 h of RA treatment, the APL cell differentiation was coupled with the cell proliferation. Although similar effects of proliferation inhibition and differentiation induction were observed among the three isomers at 10(-7) M, significant differences appeared at a concentration of 10(-8) M, 9-cis RA showed a higher activity than that of ATRA, while ATRA showed better results than 13-cis RA. Our results provide further evidence that 9-cis RA could be a promising molecule in differentiation induction of malignant cells. PMID- 7869769 TI - Detection and quantification of transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF) release by normal human megakaryocytes. AB - Transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF) are known as protein cytokines involved in differentiation as well as in maturation processes within the hematopoietic system. Both enhance the proliferation and/or collagen synthesis in fibroblasts and are found within the alpha-granules of megakaryocytes. To learn more about the regulation mechanisms involving synthesis and secretion of these cytokines it is important to develop suitable experimental conditions. We have applied the reverse hemolytic plaque assay (RHPA) to CD61+ megakaryocytes prepared from bone marrow of hematologically normal patients. By means of the RHPA, the spontaneous and stimulated secretion of TGF-beta 1 and PDGF could be analyzed at the single cell level. According to morphometric analysis, predominantly small megakaryocytes including precursors (pro- and megakaryoblasts) secrete TGF-beta 1 and PDGF under physiological conditions. Furthermore, the proportion of actively secreting megakaryocytes increased significantly following treatment with recombinant human (rh) IL-3 for 8 h. A slight induction was also appreciated after stimulation with interleukins rhIL-1 or rhIL-11. Because IL-3 as well as IL-11 are known as efficient growth factors for human megakaryocytes in vitro, our data provide insights into the regulatory mechanisms involved in megakaryopoiesis and the development of myelofibrosis. PMID- 7869770 TI - Improved detection of minimal residual leukemia through modifications of polymerase chain reaction analyses based on clonospecific T cell receptor junctions. AB - Polymerase chain reaction (PCR) techniques utilizing clonospecific T cell receptor (TCR) gamma or delta junctional regions constitute broadly applicable strategies to study the clinical relevance of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) patients. For the majority of cases current PCR protocols allow the reliable detection of one neoplastic cell among 10(4) to 10(6) normal counterparts. Occasionally, however, PCR analysis fails to reach this level of sensitivity. Here we demonstrate by means of three representative ALL cases how modifications of PCR protocols can overcome some of the limitations. Thus usage of biotinylated PCR products of TCR delta junctional regions and their direct application as templates for the generation of clonospecific probes allows the introduction of a selection step and results in a significant reduction of unspecific background signals. According to our experience as well as data from other laboratories we also recommend the usage of synthetic oligonucleotides representing TCR gamma junctions as clone-specific primers for a consecutive round of amplification rather than as clonospecific probes. Both modifications improve and facilitate the detection of MRD in leukemias characterized by TCR gamma and TCR delta recombinations. PMID- 7869771 TI - Accurate quantitation of residual B-precursor acute lymphoblastic leukemia by limiting dilution and a PCR-based detection system: a description of the method and the principles involved. AB - The detection of residual leukemia cells in the bone marrow of patients during morphologic remission has been greatly facilitated by use of the polymerase chain reaction (PCR) to amplify leukemia-specific sequences. While the current PCR strategies for estimating the amount of residual leukemia claim a detection sensitivity of one leukemia cell amongst 10(5) or 10(6) normal cells, a rigorous assessment of the relative error associated with these techniques has not been presented. We have developed a method of estimating the amount of residual leukemia in remission marrows that is analogous to the limiting dilution assays used to determine the frequency of immunocompetent cells in a responder cell population. Using this method we measured the fraction of all-or-none (i.e. positive or negative) reactions of the PCR amplification of the leukemia-specific IgH gene rearrangement in replicate samples of serial dilutions of DNA obtained from diagnostic bone marrow specimens from 15 children with B-precursor acute lymphoblastic leukemia (ALL). A sigmoid curve representing the fraction of positive PCR reactions at a given dilution of leukemia DNA was found to be the best fit to the data. The narrowness of the log-linear region of this curve prevents the direct application of the analysis methodology that has previously been described for limiting dilution assays. However, the residual leukemia burden during morphological remission in these 15 patients and in two additional patients who experienced relapse could be estimated by the described dilution analysis method using the best-fit equation. Furthermore, the data generated for diagnostic, remission and relapse marrow samples exhibited a small interspecimen variation. The results suggest that this method can reliably estimate residual leukemia over a range of five orders of magnitude. Although the PCR reaction appears to be one of the most sensitive methods for detecting residual leukemia, all techniques based on this procedure, including our own, must exhibit limitations inherent to the amplification process. Our estimates or relative error suggest that a realistic limit for the PCR estimation of residual leukemia lies in the range of one leukemia cell per 10(5) normal cells. The suggested method is rapid, technically simple and relatively inexpensive. Furthermore, the principles that it is based upon can be applied to any PCR-based strategy. PMID- 7869772 TI - Quantification of residual disease in Philadelphia-positive acute lymphoblastic leukemia: comparison of blood and bone marrow. AB - We designed a new semi-quantitative competitor-based PCR assay to assess the amount of p190 BCR-ABL mRNA in patients with Ph-positive ALL. Transcript numbers were compared in 29 paired specimens of blood and marrow collected contemporaneously from 18 patients at differing stages of disease. In general, the numbers of BCR-ABL transcripts detected in marrow in blood were not significantly different (p = 0.1). However, in four samples BCR-ABL transcripts (< 10-1000/micrograms RNA) were detected in the marrow while the blood was negative; the reverse, positive blood and negative marrow, was not seen. In a further three samples the number of BCR-ABL transcripts was more than 10-fold higher in the marrow. We measured the number of ABL transcripts/micrograms RNA in all samples as an internal standard in order to control for variations in sample quality and other parameters. For two out of the four discordant samples in which blood was PCR negative, the number of ABL transcripts/micrograms RNA detected in the marrow was substantially higher than in the blood, suggesting poor quality blood specimens. However, the ratio of BCR-ABL to ABL in marrow and blood was similar for the three discordant samples in which both tissues were PCR positive. We conclude that in general, blood and marrow contain similar BCR-ABL transcript numbers in Ph-positive ALL but some samples are discordant. Marrow is therefore the preferred tissue for residual disease studies. Quantification of ABL mRNA as an internal control is useful in the interpretation of competitive PCR data and may serve as a robust way to standardize results between laboratories. PMID- 7869773 TI - Establishment and characterization of an immature human megakaryoblastic cell line, MEG-A2. AB - We have established a novel human megakaryoblastic cell line, designated as MEG A2, from a patient with megakaryoblastic crisis of Philadelphia (Ph) chromosome positive chronic myelogenous leukemia. MEG-A2 cells showed positive phenotypes for periodic acid Schiff and alpha-naphthylbutyrate esterase reactions, but were negative for myeloperoxidase and naphthol ASD chloroacetate esterase reactions. Flow cytometric analyses of cell surface markers revealed that MEG-A2 cells had a low level of GP IIb/IIIa expression as well as apparent expressions of CD4, CD7, CD13, CD33 and CD34 antigens, but no expression of GP Ib nor glycophorin A. Stimulation with phorbol 12-myristate 13-acetate (PMA) dramatically increased the expression of megakaryocyte-related markers such as HPL-3, J15, Pit-1, Y2/51 and AN51 in MEG-A2 cells. The PMA-stimulation also induced expression of platelet peroxidase (PPO) in MEG-A2 cells on electromicroscopic observation. Proliferative responses to granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) or erythropoietin were observed, and the expression of GP IIb/IIIa was increased by stimulation with GM-CSF, IL-3, erythropoietin and interleukin-6 (IL-6). Protein S mRNA expression was seen in cultured cells on Northern blot analysis. Expression of platelet factor 4 mRNA was induced in PMA stimulated cells, and a marked accumulation of protein was observed in the culture medium. In conclusion, a new cell line, MEG-A2, belongs to the relatively immature megakaryocytic lineage and has markedly increased megakaryocytic characteristics with PMA stimulation. PMID- 7869774 TI - Low frequency of activity of P-glycoprotein (P-170) in acute lymphoblastic leukemia compared to acute myeloid leukemia. AB - The purpose of our investigations was to measure P-glycoprotein (P-170) activity in blast cells of 35 adults with acute myeloid leukemia (AML), and 24 children and adults with acute lymphoblastic leukemia (ALL) at time of diagnosis. Studies were based on a flow cytometric assay that detects efflux of the fluorescent dye rhodamine 123 (Rh123), which is transported from the cell by the P-170 pump. Dual fluorescence staining with Rh123 and phycoerythrin-labeled monoclonal antibodies allowed selective measurement of Rh123 efflux in blast cells. Samples were scored positive when the fraction of blast cells showing Rh123 efflux exceeded 10% after a 120-min incubation. Activity of P-170 was observed in 19 (54%) of the 35 AML cases and was completely blocked in the presence of multidrug resistance inhibitors. Efflux activity was significantly higher in CD34-positive AML samples (p < 0.02). All AML patients with the FAB-subtype M5 (n = 5) lacked Rh123 pumping activity (p < 0.03). The complete remission rate in response to induction chemotherapy was significantly higher for Rh123-negative (11/13, 85%) than for Rh 123-positive AML patients (4/15, 27%) (p < 0.007). At a median follow-up of 9 months overall survival was significantly shorter for Rh123-positive than for Rh123-negative patients (p < 0.05). In contrast to AML, we could detect Rh123 efflux in only two (8%) out of 24 ALL cases. The immunological subtypes of these two positive cases was of B-ALL and pre-T-ALL. Bone marrow cryostat sections from 13 AML and five ALL patients were further analyzed for staining with monoclonal antibodies MM4.17 and JSB1. Ten of 13 AML and two of five ALL cases expressed the MDR protein. Our results indicate that there is a rather low frequency of P-170 pumping activity in ALL compared with AML. Further, functional activity of P-170 contributes to chemoresistance in de novo AML. PMID- 7869775 TI - The use of cyclosporin-A in the treatment of B-chronic lymphocytic leukemia. PMID- 7869776 TI - Human monocytic leukemia expresses low levels of asparagine synthase and is potentially sensitive to L-asparaginase. PMID- 7869777 TI - Request for leukaemic samples from twins. PMID- 7869778 TI - [Malaria imported by immigrants in Catalonia]. AB - BACKGROUND: The aim of the present study was to analyze the epidemiologic aspects and particular features of malaria in immigrants in Catalonia, Spain. METHODS: All the immigrants who visited the Unit of Tropical and Imported Diseases "Drassanes" in Barcelona from endemic zones of malaria from 1990 to 1993 were studied. The diagnosis of malaria was based on the thick blood film, peripheral blood smear exam and, since 1991, the QBC (Quantitative Buffy Coat). RESULTS: One hundred three cases of malaria were diagnosed in 100 individuals from a total of 2,453 visited immigrants. Forty-four percent of the patients presented febrile syndrome, 11% cutaneous syndrome accompanied by other manifestations justifying the same, 9% presented other clinical manifestations and 36% were asymptomatic. Ninety-six percent of the subjects with parasites by Plasmodium were from sub Saharan Africa and in 2 cases, both were produced by Plasmodium falciparum, with the length of time having been in Spain at the time of diagnosis being more than one year. P. falciparum represented 70% of the total cases, followed by P. malariae (15%), P. vivax (8%), Plasmodium spp. (6%) and P. ovale (1%). CONCLUSIONS: Malaria by P. falciparum in semi-immune immigrants is not usually severe and follows an asymptomatic course in more than one third of the cases. The usual analysis for Plasmodium is recommended in immigrants from sub-Saharan Africa due to the high frequency of presentation and the absence of symptoms. Such analysis is not advised in groups from other areas except when suggestive symptoms are present. PMID- 7869779 TI - [Cost-effectiveness of the methods of smoking cessation]. AB - BACKGROUND: The cost-effectiveness of the following methods of cessation of smoking were calculated in this study: 1) medical advice, 2) medical advice and nicotine chiclets, and 3) medical advice and nicotine patches. METHODS: The costs and effectiveness of the methods of cessation of smoking compared in terms of cost per year of life gained, deducing the costs and benefits at 5%. RESULTS: The cost per year of life gained was found to be 260,000 to 434,000 pesetas in males and 441,000 to 637,000 in women for medical advice, 287,000 to 479,000 in males and 486,000 to 703,000 in females for advice and nicotine chiclets and 329,000 to 549,000 in males and 557,000 to 805,000 in females for advice and nicotine patches. Maximum efficacy was achieved with the three methods in the age group from 45-59 years in males and from 50-54 years in females. On comparison of cost and effectiveness of the methods of nicotine substitution with those calculated for medical advice the increase in cost-effectiveness was shown to be 395,000 to 658,000 in males and 668,000 to 966,000 in females for advice and chiclets and from 467,000 to 779,000 in males and 791,000 to 1,142,000 in females for advice and patches. The increase in cost-effectiveness for advice and patches versus advice and chiclets was from 539,000 to 899,000 in males and 913,000 to 1,318,000 in females. CONCLUSIONS: The efficiency of achieving the cessation of smoking is very similar for medical advice and medical advice plus nicotine chiclets and is somewhat less for medical advice and nicotine patches. The results of this study place the methods of smoking cessation among the most effective health care procedures. PMID- 7869780 TI - [Infectious endocarditis: perspectives toward 2000]. PMID- 7869781 TI - [Functioning of the Drug Institute of the German Federal Office of Health following a training period]. PMID- 7869782 TI - [Research strategy in the national health system. II. Research in health services]. PMID- 7869783 TI - [Plasma concentration of polymorphonuclear elastase as an early marker of respiratory distress syndrome]. PMID- 7869784 TI - [Pulmonary toxicity associated with treatment by gold salts]. PMID- 7869785 TI - [Efficacy of early treatment with intravenous immunoglobulins in severe forms of dermatomyositis]. PMID- 7869786 TI - [The never ending story]. PMID- 7869787 TI - XVIII National Meeting of the Spanish Society of Pharmacology. Alicante, 2-4 November 1994. Abstracts. PMID- 7869788 TI - [Psychiatric reform: Skelleftea is on the right path but worries about economics]. PMID- 7869789 TI - [The ST-reform: is the education better now with the time substituted by goals?]. PMID- 7869790 TI - [New Year's Eve at an ophthalmologic emergency unit]. PMID- 7869791 TI - [Misdiagnosis in rectal palpation in appendicitis resulted in groundless reporting]. PMID- 7869792 TI - [Tick-borne Borrelia infection. Often presented with a typical clinical picture]. PMID- 7869793 TI - [Cigarette smoking causes insulin resistance. New findings on metabolic effects of tobacco]. PMID- 7869794 TI - [Don't ignore/accept violence in health care!]. PMID- 7869795 TI - [Prevention of cardiovascular diseases in Kiruna. A research project in primary health care]. PMID- 7869796 TI - [100,000 operations in the cataract registry. Outcome and benefit is followed-up as a next step]. PMID- 7869797 TI - [Fibromyalgia. A neuro-immuno-endocrinologic syndrome?]. AB - Fibromyalgia is an enigmatic long-lasting polysymptomatic disease which has been thought to be caused by peripheral muscle dysfunction or psychological factors. Based on a clinical evaluation of a large series of in-patients and a review of international findings, the article advances the hypothesis of irreversible disturbances of the neuroimmunoendocrinological system as the main cause of this disease. The therapeutic consequences of this hypothesis are discussed. PMID- 7869798 TI - [Laparoscopic cholecystectomy. Cost-effective gallstone surgery]. PMID- 7869799 TI - Poisons control and nursing--the new Poisons Regulation, and--the Poisons Act. PMID- 7869800 TI - The power to heal colleagues and clients with a two-minute massage. PMID- 7869802 TI - Nursing, healing and natural therapies: testing the waters. PMID- 7869801 TI - Flower essences: their use in hospitals and patient care. PMID- 7869803 TI - Natural therapies: a university comes of age. PMID- 7869804 TI - Bushfire Brigade volunteers. PMID- 7869805 TI - Summary of the Health Care Complaints Act. PMID- 7869807 TI - The nursing home industry. Residential classification instrument documentation consultation for The Commonwealth Department of Health, Housing, Local Government and Community Services. PMID- 7869806 TI - Australian Nursing Council Inc. Code of conduct for nurses in Australia. PMID- 7869808 TI - Nurse in profile: Christine Thomson, A.I.N.. Interview by Peter Schwab. PMID- 7869809 TI - Establishing a private nursing practise. PMID- 7869810 TI - Nursing services in rural NSW. PMID- 7869811 TI - Quality improvement through use of medication incident reports. AB - This paper describes the background to the development of a Medication Incident Report pro forma, for use throughout the Liverpool Health Service. This pro forma is used by Medical, Pharmacy and Nursing staff to report prescription, dispensing and administration of medication errors. PMID- 7869812 TI - Discharge planning and patient education. PMID- 7869814 TI - A rural approach to wise medication usage the Nambucca Pill Spill: an overview of the medication project. PMID- 7869813 TI - Self-medication. PMID- 7869815 TI - The community health nurse. Interview by Peter Schwab. PMID- 7869816 TI - The hospital in the home. Interview by Peter Schwab. PMID- 7869817 TI - A medication strategy for nursing homes. PMID- 7869818 TI - Hugs not drugs--an alternative management tool. PMID- 7869819 TI - Pills can kill. PMID- 7869820 TI - Nurses, medication and the elderly: a time for review. PMID- 7869821 TI - Helping the elderly keep healthy: aged day care. Interview by Peter Schwab. PMID- 7869822 TI - What you should know about the Coroner's Court & other legal matters. PMID- 7869823 TI - Atrial natriuretic peptide inhibits nitric oxide synthesis in mouse macrophages. AB - The atrial natriuretic peptide (ANP) affects cardiovascular physiology, and, as has been suggested more recently, exerts immunomodulatory activities. In this context, we examined the effect of ANP on nitric oxide (NO) synthesis in murine bone marrow derived macrophages as well as in peritoneal macrophages. Cultured macrophages were stimulated with lipopolysaccharides (LPS 0.1-10 micrograms/ml) and NO synthesis was monitored by measuring increased concentrations of NO2 in the medium. In initial experiments employment of NG-monomethyl-L-arginine (L NMMA) and dexamethasone, two specific inhibitors of nitric oxide synthase (NOS), confirmed the presence of inducible NOS activity in the cells. Exposure of cells to rat ANP99-126 in the range of 10(-8) to 10(-6) M significantly decreased LPS induced NO synthesis over 24 hours of incubation. Thus, ANP may alter macrophage function by affecting their nitric oxide synthesizing pathway. PMID- 7869824 TI - The anti-tumor agent, taxol, attenuates contractile activity in rat aortic smooth muscle. AB - Using 16-20 week old female spontaneously hypertensive rats (SHRs), the effects of the antitumor agent, taxol, on vascular reactivity were examined. Taxol significantly inhibited contraction induced by phenylephrine, angiotensin II, phorbol 12,13-dibutyrate and increasing concentrations of calcium. The data suggest that taxol does not augment hypersensitivity of the vascular, but instead attenuates contractile activity and may have important implications with respect to treatment of women with both cancer and cardiovascular disease. PMID- 7869825 TI - Effects of novel 5-HT1A receptor antagonists on measures of post-synaptic 5-HT1A receptor activation in vivo. AB - The effects of two putative 5-HT1A antagonists, 4-(2'-methoxyphenyl)-1- [2'-[N (2"-pyridinyl)-p-iodobenzamido]ethyl]piperazine (p-MPPI) and 4-(2'-methoxyphenyl) 1-[2'-[N-(2"-pyridinyl)-p- fluorobenzamido]ethyl]piperazine (p-MPPF), were examined in vivo in two tests of postsynaptic 5-HT1A receptor activation, hypothermia and reciprocal forepaw treading, in the rat. Both p-MPPI (10 mg/kg, i.p.) and p-MPPF (10 mg/kg, i.p.) antagonized the hypothermia induced by the 5 HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.5 mg/kg, s.c.). Neither p-MPPI nor p-MPPF administered alone at a dose of 10 mg/kg (i.p.) induced hypothermia. Similarly, both p-MPPI (10 mg/kg, i.p.) and p-MPPF (2.5 mg/kg, i.p.) completely antagonized 8-OH-DPAT (2 mg/kg, s.c.)-induced forepaw treading in rats pretreated with reserpine (1 mg/kg, s.c., 18-24 hours prior to the experiment). p-MPPI and p-MPPF, at doses of 10 mg/kg (i.p.) did not induce forepaw treading in reserpine pretreated animals. The results of the present study demonstrate that p-MPPI and p-MPPF act as 5-HT1A receptor antagonists in these measures of postsynaptic 5-HT1A receptor activation. PMID- 7869826 TI - Vanadate increases cytosolic free calcium in rat aortic smooth muscle cells. AB - Although several studies have shown that vanadate evokes vasoconstriction whether it elevates cytosolic free calcium, [Ca2+]i, in vascular smooth muscle (VSM) cells has not been investigated. The present study shows that acute additions of low concentrations of vanadate (10-200 microM) to cultured aortic smooth muscle cells (ASMC) produced a rapid and a concentration-dependent increase in [Ca2+]i with an EC50 (mean +/- SEM) value of 42 +/- 11 microM. Inclusion of vanadate (200 microM) led to a significant increase (p < 0.05) in the peak [Ca2+]i level to 190 +/- 23 nM from a basal level of 102 +/- 2 nM. At concentrations > 200 microM, vanadate caused quenching of fura-2 fluorescence. For example, addition of 1 mM vanadate led to an apparent decrease in fluorescence by about 50% (due to a quenching effect), followed by a transient rise. H2O2, which is used in the preparation of peroxide forms of vanadate, pervanadate (PV), also produced a rise in [Ca2+]i. These data suggest that vanadate promotes vascular tone by elevating [Ca2+]i in ASMC. However, [Ca2+]i measurements made with higher concentrations of vanadate and PV, using the fura-2 method, must be interpreted with caution. PMID- 7869827 TI - Blockade of cocaine-induced conditioned place preference: relevance to cocaine abuse therapeutics. AB - Conditioned place preference/aversion testing is a behavioral method believed capable of measuring the affective (positive, neutral or negative) properties of psychoactive drugs. Cocaine injections in rats reliably produces a positive place preference. Drugs that attenuate or block this effect of cocaine have obvious potential for developing treatments to address cocaine addiction as well as to add to the scientific understanding of the mechanism of cocaine's action at the cellular level. To date, six drugs have been reported to block the expression of a cocaine-induced conditioned place preference (CPP) and this review evidences the cocaine-induced CPP blockage by the two potent L-type calcium channel blockers, isradipine and nifedipine, the two serotonin-3 receptor antagonists, MDL72222 and ICS205-930, the delta opioid receptor selective antagonist naltrindole, and lastly, a mixed opioid agonist-antagonist buprenorphine. Additional evidence relating to the blockade of other cocaine behavioral effects by these putative blockers is addressed, where appropriate, from studies employing other procedures such as drug stimulus discrimination, self administration, electrical brain stimulation and increases in locomotor activity. The significance of these findings is discussed in the context of their relevance to the development of treatment regimens to allow for cessation of cocaine abuse. PMID- 7869828 TI - Role of WDR neurons in a hind limb noxious heat evoked flexion withdrawal reflex. AB - Behavioral experiments and neurophysiological experiments, the two major types of preclinical studies which have paved the way for the development of spinal analgesia were compared under identical conditions utilizing the same animals. The results demonstrate that the activation of the wide dynamic range (WDR) neurons preceded the behavioral withdrawal reflexes, and that the activation of the WDR neurons occurred at lower stimulus temperature than that for the withdrawal reflex. The results suggest that the neuronal activation began before the behavioral reflex but also that the firing frequency of the WDR neurons at the time of the withdrawal reflex could not distinguish between non-noxious and noxious stimuli. Further study is needed to elucidate the neuronal mechanisms of the activation of the behavioral reflex. PMID- 7869829 TI - Effect of GHRP-6 and GHRH on GH secretion in rats following chronic glucocorticoid treatment. AB - The aim of our study was to investigate the effects of His-DTrp-Ala-Trp-Phe-Lys NH2 (GHRP-6) on baseline and growth hormone-releasing hormone (GHRH) stimulated growth hormone (GH) release in conscious, freely-moving rats receiving chronic glucocorticoid treatment. Animals were treated daily for seven days with either vehicle or dexamethasone (dex, 40 micrograms/day). On the day of experimentation, rats received an i.v. injection of saline or GHRP-6 followed 15 min later by an i.v. injection of saline or rat GHRH. Three doses of GHRP-6 were evaluated, 1 microgram, 4 micrograms and 25 micrograms/kg; one dose of GHRH was evaluated, 500 ng/kg. GHRP-6 increased plasma GH levels over baseline concentrations in a dose dependent fashion both in vehicle- and dex-treated rats. The GH response to GHRP 6 and GHRH was significantly less in dex-treated rats as compared to vehicle treated rats. The combined administration of GHRP-6 and GHRH did not result in any change in plasma GH levels which could not be predicted from the administration of either peptide alone. Our results show that GHRP-6 is able to stimulate GH secretion in glucocorticoid-treated rats but it is unable to counteract the glucocorticoid-induced inhibition of GH secretion. PMID- 7869830 TI - Estrogen modulates the inducible expression of platelet-derived growth factor mRNA by monocyte/macrophages. AB - We examined the effects of estrogen, 12-O-tetradecanoylphorbol 13 acetate (TPA), and lipopolysaccharide (LPS) on the gene expression of platelet-derived growth factor (PDGF) by the monocyte/macrophage cell line, THP-1. THP-1 cells were exposed to TPA for 48 or 96 hours to induce differentiation. Some were treated with LPS in the last 3 hours and/or ethinyl estradiol (estrogen) (10(-9) M) in the last 20 hours. Total cellular RNA was isolated and cDNA was synthesized and then coamplified (with an internal control, beta-actin, product size 1126 bp) using polymerase chain reaction (PCR) and a set of primers for PDGF-A (product size 225 bp), PDGF-B (217 bp), or PDGF beta-receptor (PDGF-R) (228 bp). The products were separated on an agarose gel and the ratios of radioactivity incorporated into PDGF PCR products to beta-actin products were used to assess the relative changes in the levels of PDGF mRNA abundance in response to various inducers. TPA induced the expression of PDGF-A mRNA, whereas LPS had no effect. Treatment of TPA-stimulated cells with estrogen caused a 61% and 190% increase in PDGF-A mRNA (p < 0.05) at 48 and 96 hours, respectively. Addition of estrogen to cells treated with both TPA and LPS did not cause any significant change in the amounts of the transcripts. In contrast to PDGF-A mRNA, attempts to visualize and estimate PDGF-B and PDGF-R mRNA were unsuccessful. This was probably due to low levels of these transcripts in THP-1 cells. The results indicate that estrogen modulates PDGF-A gene expression by monocyte/macrophages and suggest that estrogen may influence atherogenesis at the vascular level. PMID- 7869831 TI - Effects of HL-004, a novel ACAT inhibitor, on cholesterol accumulation and removal in cultured smooth muscle cells from stroke-prone spontaneously hypertensive rats (SHRSP). AB - The cholesterol metabolism of cultured smooth muscle cells (SMC) from the thoracic aorta of SMC from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) was compared. SMC from SHRSP had a higher acylCoA:cholesterol acyltransferase (ACAT) activity and accumulated more cholesterol than those from WKY. By using SMC from SHRSP, the effects of a novel ACAT inhibitor, HL-004, on the accumulation and removal of cholesterol were investigated. HL-004 inhibited microsomal ACAT activity from rabbit liver, intestine, aorta, and cultured SMC of SHRSP with 50% inhibition (IC50) values of 2.2, 1.7, 7.9, and 20 nM, respectively. HL-004 suppressed the accumulation of the intracellular cholesteryl ester (CE), but did not affect the intracellular free cholesterol (FC) content. Removal of cholesterol from the lipid-loaded SMC was accelerated by HL-004. These effects of HL-004 on cholesterol levels showed a good parallel to ACAT inhibition. It would thus appear that the suppression of cholesterol accumulation and the removal of cholesterol in SMC by HL-004 can be attributed to its ACAT inhibition in the cell, which reduces the content of intracellular CE. PMID- 7869832 TI - BW2258U89: a GRP receptor antagonist which inhibits small cell lung cancer growth. AB - The ability of reduced peptide bond analogues of gastrin releasing peptide (GRP) to antagonize small cell lung cancer (SCLC) GRP receptors was investigated. BW462U89, BW1023U90, BW2123U89 and BW2258U89 inhibited binding of (125I-Tyr4) BN to NCI-H345 cells with IC50 values of 5, 6, 140 and 10 nM respectively. The GRP analogues had no effect on basal cytosolic Ca2+ but inhibited the increase caused by 10 nM BN. BW462U89 reversibly blocked the increase in cytosolic Ca2+ caused by BN. The GRP analogues (1 microM) inhibited NCI-H345 colony formation in the absence or presence of 10 nM BN. Also, BW2258U89 (0.4 mg/kg, s.c. daily) inhibited xenograft growth in nude mice. These data indicate that BW2258U89 inhibits SCLC growth in vitro and in vivo. PMID- 7869833 TI - The effects of extracellular pH on intracellular pH, Ca2+ and tension of canine tracheal smooth muscle strips. AB - The effects of changes in extracellular pH (pHo) on intracellular Ca2+ concentration ([Ca2+]i) or intracellular pH (pHi) were measured simultaneously with muscle tension in canine tracheal smooth muscle strips. [Ca2+]i and pHi were measured using the fluorescent dyes fura-2 and BCECF, respectively. During high K(+)-induced contractions (24.2, 36.4 or 72.7 mM) at pH 7.4, pHo was changed to 7.8 or 7.0 with NaOH or HCl, respectively. Induced changes in pHi were equal to approximately 50% of the changes in pHo. Alkalinization significantly increased [Ca2+]i and enhanced muscle contraction at all concentrations of K+ but did not alter the relationship between muscle tension and [Ca2+]i. Acidification significantly decreased [Ca2+]i without changing muscle tone; hence, the muscle tension-[Ca2+]i relationship was shifted to the left. These results suggest that changes in pHo can alter airway smooth muscle tone by changing [Ca2+]i and pHi. PMID- 7869834 TI - Multiplicative interaction between intrathecally and intracerebroventricularly administered morphine for antinociception in the mouse: involvement of supraspinal NMDA but not non-NMDA receptors. AB - Concurrent administration of morphine to both supraspinal and spinal sites produced a multiplicative (synergistic) interaction for antinociception. The purpose of this study was to determine if supraspinal glutaminergic receptors are involved in the multiplicative interaction for antinociception induced by morphine. The antinociception was assessed by the tail-flick test. Effect of MK 801 [(+/-)-5-methyl-10, 11-dihydro-5H-dibenzo (a,d)cyclohepten-5,10-imine maleate], a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, or CNQX (6-Cyano-7-nitroquinoxaline-2,3-dione), a competitive non-NMDA receptor antagonist on inhibition of the tail-flick response induced by a combined i.t. and i.c.v. administration of morphine was studied. Either i.t. or i.c.v. administration of morphine alone at the dose of 0.2 microgram slightly increased inhibition of the tail-flick response. However, concurrent i.t. and i.c.v. injections of morphine at the dose of 0.2 microgram increased the inhibition of the tail-flick response in a synergistic manner. Various doses of MK-801 (0.01-1 microgram) or CNQX (0.05-0.5 microgram) pretreated i.c.v. alone did not show any antinociceptive effect. MK-801 pretreated i.c.v. for 10 min dose-dependently attenuated the inhibition of the tail-flick response induced by concurrent i.t. and i.c.v. injections of morphine. However, CNQX pretreated i.c.v. for 10 min did not affect the inhibition of the tail-flick response induced by concurrent i.t. and i.c.v. injections of morphine. Our results suggest that supraspinal NMDA but not non-NMDA receptors are involved in mediating the antinociception produced by morphine-induced multiplicative interaction between spinal and supraspinal sites. PMID- 7869835 TI - Diversity of neuronal nicotinic acetylcholine receptors: lessons from behavior and implications for CNS therapeutics. AB - Although the molecular biology of neuronal nicotinic acetylcholine receptors (nAChRs) provides evidence for multiple receptor subtypes, few selective pharmacological tools exist to identify these subtypes in vivo. However, the diversity of behavioral effects of available nAChR agonists and antagonists reviewed in this paper suggests that neuronal nAChR subtypes may play distinct roles in a variety of behavioral outcomes. Further characterization of the behavioral effects of the activation of discrete nAChR subtypes may eventually provide information useful in designing selective nAChR ligands targeting a variety of CNS disorders. PMID- 7869837 TI - Pancreatic polypeptide enhances plasma glucocorticoid concentration in rats: possible role in hypoglycemic stress. AB - The acute bolus intraperitoneal (i.p.) administration of pancreatic polypeptide (PP) dose-dependently enhanced the plasma concentration of corticosterone (PBC) in hypophysectomized/ACTH replaced rats, but not that of aldosterone. Minimal and maximal effective doses were 10(-12) and 10(-10) mol/rat, respectively, and maximal PBC increase occurred between 60 and 120 min after PP injection. Insulin (1 U/kg, i.p.) evoked a net decrease in the blood glucose concentration, and marked rises in the plasma levels of PP and PBC, that attained their maximum at 60 and 120 min, respectively. The effects of insulin were annulled by the simultaneous injection of 0.5 mg/kg atropine. The effects of 1 U/kg insulin and 10(-10) mol/rat PP on PBC were not additive; atropine did not affect PBC response to PP or PP plus insulin, though annulling that to insulin alone. Taken together these findings suggest that PP plays a physiologic role in the rat as modulator of the adrenal response to the insulin-induced hypoglycemic stress. PMID- 7869836 TI - Brain regional differences in glycine reversal of ethanol-induced inhibition of N methyl-D-aspartate-stimulated neurotransmitter release. AB - The present study investigated the interaction between glycine and ethanol on N methyl-D-aspartate (NMDA)-stimulated neurotransmitter release in hippocampal, cerebrocortical, and striatal slices from rat brain. Some, but not all, previous studies have shown that glycine may reverse the inhibitory effect of ethanol on NMDA receptors. Hippocampal or cortical slices were prepared and prelabelled with [3H]norepinephrine, and striatal slices were labelled with [3H]dopamine. Stimulation of the slices with 500 microM NMDA for two minutes caused a significant release of [3H]neurotransmitter in each brain region above basal. Ethanol (60 mM) significantly inhibited the NMDA-stimulated release of neurotransmitter from all brain regions. Addition of glycine (0.3-3 microM) to the buffer bathing the slices had no effect on the inhibitory effect of ethanol in hippocampus or cortex. However, in striatal slices, 0.3 and 1.0 microM glycine added to the buffer reversed the inhibitory effect of ethanol on NMDA-stimulated [3H]dopamine release without having any effect on either basal or NMDA-stimulated release by itself. These results show that the interaction between ethanol and glycine varies in different brain regions. Therefore interpretation of the potential inhibitory effect of ethanol on NMDA receptor function in vivo should consider brain region and local concentrations of glycine. PMID- 7869838 TI - Effects of cholecystokinin on chicken cecal motility: mechanisms involved. AB - The aims of this work are to characterize the effects of cholecystokinin (CCK) on chicken ceca and to study in vitro the mechanisms through which such actions are mediated. Longitudinal and circular cecal strips kept in vitro in organ baths were responsive to CCK sulphated octapeptide (CCK-8s). On longitudinal strips the response consisted of a fast phasic contraction followed by a sustained increase in tone which was dose dependent and decreased markedly in the presence of tetrodotoxin (TTX). Ketanserin (10(-5) M) also caused a decrease in the CCK-8s response. CCK tetrapeptide (CCK-4) and CCK unsulphated octapeptide (CCK-8ns) induced slightly less contractile effects at concentrations of 2 x 10(-6) M only. L365,260 and L364,718 decreased the response of longitudinal strips to CCK-8s with similar efficacy. On circular strips CCK-8s caused rhythmic phasic contractions of dose dependent amplitude and frequency, and both effects were resistant to TTX. The EC50 for the amplitude was about 4 times higher than that for the frequency. CCK-8ns (2x 10(-6) M) also caused phasic contractions, whereas the same concentrations of CCK-4 did not elicit any motor effects. L365,260 and L364,718 showed different efficacy in decreasing amplitude or frequency of contraction. These results suggest that 1) Both muscularly and neurally located CCK receptors are present on the longitudinal layer of chicken ceca whereas only muscular receptors are present on the circular muscle. 2) 5HT2 receptors seem to be involved in the neurally mediated CCK-8s response observed in the longitudinal layer. 3) The different potency of CCK-8s, CCK-8ns and CCK4 to induce contractile effects and of the CCK-A and CCK-B antagonists to block such effects suggests the existence of two different CCK receptors on the circular layer. PMID- 7869839 TI - Enhanced catecholaminergic and serotoninergic activity in rat brain from weaning to sexual maturity: rationale for prophylactic (-)deprenyl (selegiline) medication. AB - Food deprived rats in the late developmental phase of life (2 months of age) are significantly more active than those in the early postdevelopmental phase (4 months of age), pointing to enhanced catecholaminergic activity during the developmental phase. We therefore measured the resting release of dopamine from the striatum, substantia nigra and tuberculum olfactorium, and of noradrenaline from the locus coeruleus, as an indicator of the basic activity of catecholaminergic neurons in the brain, in 2,4,8,16 and 32 weeks old male and female rats. We also measured the release of serotonin from the raphe. Both in male and female rats, the resting release of transmitters from brain catecholaminergic and serotoninergic neurons between weaning and the end of the 2nd month of age, i.e. during the crucial developmental phase of their life, was significantly higher than either before or after that period, signalling a transition from a developmental to a postdevelopmental (aging) phase of life and indicating that safe and effective measures are needed to maintain the catecholaminergic system at a higher activity level during the postdevelopmental phase. Daily administration of low doses (0.01-0.25 mg/kg) of (-)deprenyl for 21 days significantly enhances the resting release of catecholamines and diminishes that of serotonin, providing a rationale for prophylactic medication with this drug during the postdevelopmental lifespan. We also show that (-)methamphetamine, the parent compound of (-)deprenyl and (-)1-phenyl-2-propylaminopentane (PPAP), a deprenyl analogue free of MAO-B inhibitory potency but otherwise possessing the same pharmacological profile as (-)deprenyl, act similarly, furnishing direct evidence that enhancement of catecholaminergic activity in the brain by multiple, small dose administration of (-)deprenyl is unrelated to MAO-B inhibition. PMID- 7869840 TI - Hepatic mitochondrial enzyme activity and serum amino acid composition in rats treated with tumor necrosis factor. AB - The biochemical integrity of hepatocellular mitochondria was investigated in rats treated with small doses of human recombinant tumor necrosis factor-alpha (Hur TNF;50-100 micrograms/kg/d injected intraperitoneally for 5 d) by measuring the activities of three mitochondrial enzymes, glutamate dehydrogenase, succinate dehydrogenase and malate dehydrogenase. The activity of glutamate dehydrogenase (a mitochondrial matrix enzyme) was 20% to 34% lower than that of control rats (P = 0.02 to 0.0003). The activities of succinate dehydrogenase (an inner mitochondrial membrane enzyme) and malate dehydrogenase (a mitochondrial matrix and cytosolic enzyme) showed no significant difference. The effect of TNF on serum amino acid composition was studied using pair-fed, weight-matched partners to eliminate any effect of the reduction of food intake due to TNF treatment. The results for the TNF-treated rats showed a significant (P < 0.05) increase in the concentration of 12 of the 21 amino acids measured (range = 33% to 140%). Of these, major increases were observed in the urea cycle intermediates, ornithine (140%) and arginine (59%), as well as proline (94%), alanine (41%), valine (61%), leucine (64%), isoleucine (63%), and aspargine (71%). Since previous studies have shown that the treatment of rats with the same low doses of TNF did not cause any change in mitochondrial ultrastructure detectable by electron microscopy, these results suggest that significant biochemical changes in amino acid metabolism occur as a result of a decrease in mitochondrial glutamate dehydrogenase activity. PMID- 7869841 TI - Characterization of the binding of [125I]L-735,286: a new nonpeptide angiotensin II AT1 receptor radioligand. AB - [125I]L-735,286, a new potent and AT1-selective nonpeptide angiotensin II receptor radioligand, bound saturably to whole adrenal membranes. Scatchard and Hill plot analysis indicates a single class of high affinity (Kd = 0.5 nM) binding sites. The potencies of various angiotensin II agonists and antagonists in displacing specific [125I]L-735,286 binding are in good agreement with their potencies in displacing the binding of [125I]Sar1,Ile8-AII to adrenal AT1 receptors. The AT2 selective ligand, PD121981 had no effect on specific [125I]L 735,286 binding. In autoradiographic studies using rat kidney slices, specific labeling of [125I]L-735,286 was abolished by coincubation with saralasin. Collectively, the data indicated that [125I]L-735,286 represents a new, potent nonpeptide antagonist radioligand suitable for the study of angiotensin II AT1 receptors. PMID- 7869842 TI - Effects of buspirone on influenza A virus infection in stressed mice. AB - Experiments were conducted to evaluate the effects of chronic buspirone (1 mg/kg/day) on the influenza A (PR-8/34) virus specific immune injury in CD-1 mice exposed to a chronic auditory stressor. Treatment with buspirone resulted in a decrease of the stress-induced increase of virus titers and pulmonary vascular permeability as well as in a reduction of the mortality of mice. PMID- 7869843 TI - Bosentan antagonizes the effects of endothelin-1 on rat gastric blood flow and mucosal integrity. AB - Bosentan, a new type of orally effective, mixed (ETA+ETB) endothelin receptor antagonist has been recently introduced and tested in a variety of experimental models. We studied the effect of bosentan on the changes in gastric mucosal hemodynamics and mucosal integrity, induced by the exogenous application of endothelin-1, in rats. Bosentan (10 mg/kg iv) pretreated rats were injected with endothelin-1 (500-1000-2000 pmol/kg, iv) and gastric mucosal hemodynamics were monitored. After combined oral (30 mg/kg) and systemic pretreatment with bosentan we studied the effects of submucosal injection of endothelin-1 (50 pmol) on blood flow and gastric mucosa. Bosentan antagonized the vasodilator, vasoconstrictor and ulcerogenic effects of endothelin-1 in the rat gastric mucosa. These results show that bosentan can be a useful probe in the study of endogenous endothelin in the gastrointestinal tract. PMID- 7869844 TI - Cloning of a human kappa opioid receptor from the brain. AB - By using a rat kappa opioid receptor cDNA as a probe to screen a human brain cDNA library, we isolated a 4.0-kb clone (z115) which encompasses a major portion of a human kappa opioid receptor (hkor), extending from the amino acid residue #6 to the 3'-untranslated region. The extreme 5'-region 232-bp fragment of z115 was used as a probe to screen a human genomic DNA library. A 1.6-kb fragment (d2) of one positive clone was found to extend from 5'-untranslated region to beyond the exon/intron junction at residue Arg86. The genomic DNA fragment d2 and the cDNA clone z115 were assembled to generate a clone (d2-z115) containing the entire coding sequence of hkor. Clone d2-z115 has an open reading frame of 1140 bp, which encodes for a 380-amino acid protein. The deduced amino acid sequence has 93.9% and 93.2% identity to rat and mouse kappa receptors, respectively. It also displays approximately 60% identity to both human mu and delta receptors. Northern blot analysis showed that in the human brain there was a single hkor mRNA transcript of 6.0 kb. Among brain regions examined, the amygdala, caudate nucleus, hypothalamus and subthalamic nucleus contained high levels of hkor mRNA. Hkor was cloned into the expression vector pBK-CMV and transiently expressed in COS-1 cells. Hkor had high affinity for [3H] diprenorphine, a nonselective opioid antagonist, and displayed stereospecific binding to naloxone. kappa selective ligands (U50,488H and nor-BNI) had high affinities, whereas mu and delta selective ligands bound with much lower affinities. Dynorphin A (1-17) and alpha neoendorphin, both endogenous kappa peptides, bound with high affinities. These binding characteristics confirmed that hkor is a kappa receptor, most likely kappa 1 type. Cloning of the human kappa receptor allows investigation of interactions of compounds with the human receptor, instead of rodent receptors, for development of better therapeutic agents. PMID- 7869845 TI - Intravenous administration of large dosages of adenosine or adenosine triphosphate with minimal blood pressure fluctuation. AB - Hemodynamic responses, blood gas, and metabolic changes were assessed when large dosages of a pre-mixed solution of adenosine or adenosine triphosphate (ATP) with catecholamine were intravenously administered in the conscious, spontaneously breathing rabbit. The present study offers a simple and effective approach to enabling safe administration of large doses of the potent vasodilators, adenosine or ATP with minimal cardio-respiratory and metabolic changes. PMID- 7869846 TI - Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. AB - CDP-choline, supplied exogenously as citicoline, has beneficial physiological actions on cellular function that have been extensively studied and characterized in numerous model systems. As the product of the rate-limiting step in the synthesis of phosphatidylcholine from choline, CDP-choline and its hydrolysis products (cytidine and choline) play important roles in generation of phospholipids involved in membrane formation and repair. They also contribute to such critical metabolic functions as formation of nucleic acids, proteins, and acetylcholine. Orally-administered citicoline is hydrolyzed in the intestine, absorbed rapidly as choline and cytidine, resynthesized in liver and other tissues, and subsequently mobilized in CDP-choline synthetic pathways. Citicoline is efficiently utilized in brain cells for membrane lipid synthesis where it not only increases phospholipid synthesis but also inhibits phospholipid degradation. Exogenously administered citicoline prevents, reduces, or reverses effects of ischemia and/or hypoxia in most animal and cellular models studied, and acts in head trauma models to decrease and limit nerve cell membrane damage, restore intracellular regulatory enzyme sensitivity and function, and limit edema. Thus, considerable accumulated evidence supports use of citicoline to enhance membrane maintenance, membrane repair, and neuronal function in conditions such as ischemic and traumatic injuries. Beneficial effects of exogenous citicoline also have been postulated and/or reported in experimental models for dyskinesia, Parkinson's disease, cardiovascular disease, aging, Alzheimer's disease, learning and memory, and cholinergic stimulation. PMID- 7869847 TI - Glipizide stimulates sympathetic outflow in diabetes-prone mice. AB - The purpose of the present study was to determine if the oral hypoglycemic agent glipizide influenced sympathetic outflow in diabetes-prone mice. C57BL/6 (diabetes-prone) and diabetes-resistant (A/J) were treated with saline or glipizide, and sympathetic outflow determined by the fall in organ norepinephrine content after synthesis inhibition with alpha-methyl-para-tyrosine. Sympathetic outflow to the liver and pancreas were slower in Bl/6 mice than in control A/J. Glipizide increased sympathetic outflow to the pancreas in both strains of mice, but did not influence outflow to other organs significantly. The results of this study suggest that glipizide can influence central glucoregulatory mechanisms after peripheral administration. PMID- 7869848 TI - Comparative studies of antiplatelet activity of nonsteroidal antiinflammatory drugs and new pyrazine CH- and NH-acids. AB - Nine known nonsteroidal antiinflammatory drugs (NSAID) and three new pyrazine derivatives possessing an active methylene moiety (pyrazine CH/NH-acids) were tested with regards to their in vitro and in vivo antiplatelet activity. Concentrations of the agents were determined which caused 25% and 50% inhibition of aggregation of human blood platelets induced by fixed concentrations of ADP, collagen and epinephrine. The in vivo test consisted in determination of percent protection of mice from pulmonary microembolism caused by injection of a mixture of collagen and epinephrine. The in vitro antiaggregatory activity of the agents studied was rather low, excepting the inhibition of the collagen-induced aggregation by ketoprofen. Several NSAID and two new pyrazine CH/NH-acids appeared highly potent antithrombotic agents in vivo. Activity of NSAID expressed as percent protection against lung thromboembolism in the mouse was demonstrated to depend quantitatively on acid properties of the agents. The new chemical class of pharmacologically active agents, pyrazine CH/NH-acids, offers an original pharmacophore which is distinctive from the carboxylic or enolic functionalities typical for the established NSAID, and as such, may be devoid of some disadvantages of known antiplatelet drugs. PMID- 7869849 TI - Cocaine and benzoylecgonine constrict cerebral arteries by different mechanisms. AB - This study was designed to determine possible mechanisms underlying the vasoconstrictor activity of cocaine and its principal metabolite, benzoylecgonine (BE) in cat isolated cerebral arteries. The arteries constricted significantly in response to single doses of cocaine, BE and norepinephrine (NE; (P < 0.05). After 6-OHDA treatment to remove adrenergic nerve endings, NE-induced constrictions were essentially unchanged from those before treatment. Denervated arteries exposed to cocaine dilated significantly (P < 0.05) but those exposed to BE constricted as much as before denervation. Following exposure to prazosin and yohimbine, arterial constrictions to NE and cocaine were significantly reduced from control (P < 0.05) but the BE-induced constriction was unchanged. Ryanodine eliminated the cocaine-induced contraction (P < 0.05) whereas verapamil eliminated the BE response (P < 0.05). These data suggest that while cocaine's vasoconstrictor action may be significantly mediated through adrenergic transmission, BE may act through a mechanism involving calcium (Ca2+) channels. Cocaine levels peak and decline in the body more rapidly than BE levels which can remain detectable for days. This study suggests there may also be different pharmacological mechanisms as well as temporal differences underlying the vasoreactivity of these two substances. Our findings may have implications for pharmacological management of cocaine-induced toxic vascular events. PMID- 7869850 TI - Tyrosine metabolism in users of oral contraceptives. AB - Brain noradrenaline takes part in the regulation of several brain functions. The formation of brain noradrenaline depends on brain tyrosine (Tyr) levels, which associates with the ratio in plasma of Tyr to other large, neutral amino acids (LNAA). Tyr metabolism has been studied in users of the new generation combined oral contraceptives (OC) and comparable controls at the follicular, mid-cycle, and luteal phases of the menstrual cycle. OC users showed significantly increased plasma Tyr transaminase activity, and significantly decreased plasma Tyr and Tyr/LNAA levels at mid-cycle and luteal phase, whereas plasma total 3-methoxy-4 hydroxyphenylglycol (MHPG) was not affected. Following an oral protein load, the area under the curve in plasma of Tyr and Tyr/LNAA in OC users at the luteal phase were 43% and 29%, respectively, of control levels. The results suggest that the decreased Tyr availability to the brain in OC users may result in a substrate limited reduction of brain noradrenaline formation, which, secondarily, may contribute to disturbances of mood, coping mechanisms, and appetite in susceptible subjects. PMID- 7869851 TI - Dietary cholesterol supplementation in the spontaneously diabetic rat. AB - Dietary cholesterol supplementation was used to increase serum cholesterol concentration in diabetic and non-diabetic rats. With the use of numerous dietary formulations, extremely elevated serum cholesterol concentrations and gastrointestinal intolerance were found. We conclude that there are unacceptable side effects with a vast number of exogenous cholesterol supplemented diets which preclude standard and long-term usage. PMID- 7869852 TI - Autonomic control of the regional hemodynamic response to scald. AB - Ultrasonic flow probes were placed around the ascending aorta and each femoral artery of dogs to record cardiac index and femoral blood flow, respectively. Intravenous hexamethonium (n = 5) produced 30% decreases in systemic mean arterial pressure and in cardiac index, and a 14% increase in femoral blood flow, effects that waned over time, consistent with the half-life of the agent. Without hexamethonium, hind paw scalding with boiling water for 5 sec (n = 5) caused a marked increase in ipsilateral femoral artery blood flow (70.7 +/- 8.9 ml/min pre burn vs 243.7 +/- 23.7 ml/min 5 min post-burn) that persisted for the 3 hr observation period. Contralateral femoral blood flow, systemic mean arterial pressure, and cardiac index were unchanged. Compared to burn only dogs, pre-burn treatment with hexamethonium (n = 6) blunted the femoral vasodilator response to burn (78.8 +/- 9.7 ml/min pre-burn vs 116.5 +/- 7.5 ml/min 5 min post-burn). These data suggest that postganglionic autonomic nerves are at least partially responsible for mediation of the regional vasodilator response to thermal injury. PMID- 7869853 TI - HDL3-mediated cholesterol efflux from cultured enterocytes: the role of apoproteins A-I and A-II. AB - High density lipoproteins (HDL) were recently demonstrated in an enterocyte model (CaCo-2 cells) to mediate reverse cholesterol transport by retroendocytosis. The present study was carried out to define the role of the major HDL apoproteins (apo) A-I and apo A-II in this pathway. HDL3 was fractionated by heparin affinity chromatography into the two main fractions containing either apo A-I only (fraction A) or both apo A-I and apo A-II (fraction B). In addition, liposomes were reconstituted from purified apo A-I or apo A-II and dimyristoyl phosphatidylcholine. The cell binding properties and cholesterol efflux potential were studied in the lipoprotein fractions and the liposomes. Both fractions exhibited similar maximal binding capacities of 4427 (A) and 5041 (B) ng/mg cell protein, but their dissociation constants differed (40.5 and 167.7 micrograms/mL, respectively). Fraction A induced cholesterol efflux and stimulated cholesterol synthesis more than did fraction B. Fraction A mobilized both cellular free and esterified cholesterol, whereas fraction B preferentially mobilized cholesteryl esters. Liposomes, containing either apo A-I or apo A-II, showed specific binding, endocytosis and endosomal transport, and were released as intact particles. Apo A-I liposomes also mediated cholesterol efflux. In conclusion, there is evidence that the HDL3 subfractions A and B, as well as reconstituted liposomes containing either apo A-I or apo A-II, were specifically bound and entered a retroendocytosis pathway which was directly linked to cholesterol efflux. Quantitatively, the apo A-I subfraction appeared to play the dominant role in normal enterocytes. The apo A-II content of fraction B was related to the mobilization of cholesteryl esters. PMID- 7869854 TI - The effects of clofibrate and bezafibrate on cholesterol metabolism in the liver of the male rat. AB - Fibric acid derivatives are used to treat hyperlipidemia and have wide ranging effects on lipid metabolism. The action of these compounds on cholesterol esterification, catalyzed by acyl-coenzyme A:cholesterol acyltransferase (ACAT), has been quite widely studied, but their effect on cholesteryl ester hydrolysis and the enzyme neutral cholesteryl ester hydrolase (nCEH) has been largely ignored. Male rats were therefore fed for 10 d on a standard chow diet supplemented with either clofibrate or bezafibrate, to study their effects on plasma lipid levels and hepatic cholesterol metabolism. Plasma triacylglycerols were not significantly altered by these diets, but bezafibrate significantly lowered plasma cholesterol levels (29.7%, P < 0.01). When expressed per unit weight of DNA, both fibrates reduced the hepatic content of triacylglycerol, cholesterol and cholesteryl esters (40, 18.7, 16.5 and 66.7, 28.6, 34.2% for clofibrate and bezafibrate, respectively). ACAT activity was significantly reduced by both drugs, but clofibrate (65% inhibition) was more effective than bezafibrate (35% inhibition). The most dramatic effect of the diets was a marked increase in the activity of both the microsomal and the cytosolic nCEH. When expressed on a whole liver basis, the effect of bezafibrate on the cytosolic enzyme (13.6-fold increase in activity) was much greater than that of clofibrate (4.8-fold increase). Increases in the activity of a cytosolic protein that inhibits the activity of nCEH were also noted, but these changes were relatively small. The results suggest that the activation of nCEH, in combination with the inhibition in ACAT activity, contributes to a decrease in the cholesteryl ester content of the liver which may influence the secretion of very low density lipoprotein. PMID- 7869855 TI - Liver, serum and adipose tissue fatty acid composition in suckling Zucker rats. AB - Young adult obese Zucker rats have altered tissue fatty acid (FA) composition. The present study was aimed at determining whether such changes were seen in either liver, serum or adipose tissue obtained from 17-day-old obese (fafa) rats in comparison to both homozygous (FaFa) and heterozygous (Fafa) lean rats. Body weights of obese pups (30.3 g) were significantly greater than those of homozygous lean rats (25.2 g) (P < 0.05). Liver weight and lipid content were similar in all groups. Inguinal fat pad weight and lipid content were greatest in obese pups (573 mg) followed by heterozygous lean pups (303 mg); homozygous lean pups (146 mg) had the lowest values. There were no differences among the groups in hepatic FA composition in either triacylglycerol (TG) or phospholipid fractions. Serum TG was similar among the groups, while serum phospholipid was greater (P < 0.05) in obese (269 mg/dL) than in homozygous lean pups (184 mg/dL); heterozygous lean pups had an intermediate value not significantly different from either homozygous group. On a percent basis, there were no differences in FA composition in either serum lipid fraction among the three groups. There were a number of significant differences in adipose tissue FA composition between the groups on a percent basis. The adipose tissue FA composition on a percent basis reflected that of maternal milk. The results indicate that suckling obese Zucker rats do not have tissue FA profiles that are characteristic of essential FA deficiency. PMID- 7869856 TI - Composition and structure of triacylglycerols in brown adipose tissue of rats fed fish oil. AB - This study examines the incorporation of highly unsaturated n-3 fatty acids (HUFA) into triacylglycerols (TAG) of brown adipose tissue (BAT), and their effect on the positional distribution of saturated (SFA) and of unsaturated (UFA) 16- or 18-carbon fatty acids. To this end, rats were fed a fish oil diet for up to four weeks. The stereospecific analysis of TAG was based on generation of sn 1,2- and sn-2,3-acylglycerols by Grignard degradation, followed by synthesis of phosphatidic acid and specific hydrolysis with phospholipase A2. From the end of the first week of fish oil feeding, a steady-state in the fatty acid composition of TAG in BAT was reached. HUFA concentration increased 30-fold, mainly at the expense of n-9 UFA and of SFA. The amount of SFA decreased selectively at position 3, where these fatty acids were progressively replaced by n-3 HUFA. By contrast, the amount of UFA decreased at all positions, and their positional distribution was not affected. About 60% of HUFA was incorporated at position 3. Nearly twice as much 22:6n-3 was incorporated into TAG than had been previously observed in white adipose tissue (WAT) [Leray, C., Raclot, T., and Groscolas, R. (1993) Lipids 28, 279-284]. At the steady-state, the distribution of HUFA was characterized by high proportions of 22:6n-3 and 20:5n-3 in position 3. Moreover, in each position of TAG, a steady level was reached rapidly (within 1 wk).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869857 TI - Absorption of isomeric, palmitic acid-containing triacylglycerols resembling human milk fat in the adult rat. AB - The effect of the positional distribution of palmitic acid (16:0) in triacylglycerols (TAG) on 16:0 apparent absorption in adult rats was investigated. The rats were fed two diets which contained 30 energy % as fat with identical total fatty acid compositions, both containing 30% 16:0. The Betapol diet contained TAG with 73% of total 16:0 in the sn-2 position, the control diet contained TAG with 6% of total 16:0 in the sn-2 position. After six weeks on these diets, the rats were killed two or six hours after the last meal, and the small intestine was removed, cut into 10-cm segments, and the fatty acid composition of the segment's contents was determined. At both time points the amount of 16:0 in the intestinal segments starting at 40 cm from the stomach was much lower in the animals fed Betapol than in the animals fed the control diet. Overall absorption of 16:0 and stearic acid was significantly greater in the Betapol group. Absorption of oleic and linoleic acid from the small intestine was similar in both groups, although the overall absorption was significantly greater in the animals fed Betapol. Total fat absorption was significantly higher in the Betapol-fed rats than in the control-fed rats. No effect on calcium and nitrogen absorption, on plasma total cholesterol and TAG levels, and on bodyweights (growth) was seen. The data demonstrate that the positional distribution of the fatty acids in the TAG molecule affects the site of absorption in the small intestine and particularly the net absorption of saturated fatty acids. PMID- 7869858 TI - n-3 fatty acids inhibit defects and fatty acid changes caused by phenytoin in early gestation in mice. AB - Our previous work has shown that n-3 fatty acids exert a protective effect against phenytoin-induced cleft palate when phenytoin was administered midgestation [gestational days (GD) 12 and 13] to CD-1 mice. The effects of dietary n-3 fatty acids on phenytoin teratogenicity were investigated at an earlier gestational period (GD 9) to examine whether n-3 fatty acids could exert protective action against other teratogenic effects of phenytoin apart from cleft palate. The effect of phenytoin exposure on maternal hepatic polyunsaturated fatty acid composition was also studied since delta 6 desaturase activity has been shown to be modified by pharmacological action. Female CD-1 mice were fed a standard laboratory diet (SLD), safflower oil (SAFF) or a cod liver/linseed oil (CLO/LO)-based diet for three weeks prior to impregnation and throughout pregnancy. Pregnant mice were administered a single i.p. dose of phenytoin on GD 9, and teratological assessments were performed on GD 19. Tissues were harvested on GD 10 for maternal hepatic phospholipid fatty acid analysis from another group of phenytoin-treated mice. The CLO/LO and the SLD mice, as compared to the SAFF fed animals, showed a reduction in total malformations and fetal growth retardation due to phenytoin. Open eye defect was the only anomaly induced by phenytoin in the CLO/LO fetuses while phenytoin produced a variety of malformations in the SAFF fetuses such as tail defects, cleft palate, open eye and absence or blockage of the ureter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869859 TI - Effects of low casein and fish oil on hyperlipidemia and proteinuria in nephritic rats. AB - The effects of amino acid-fortified low casein and fish oil (FO) diets on hyperlipidemia and proteinuria were studied in rats with nephrotoxic serum nephritis. After an antiserum injection, rats were maintained for 14 d on four different experimental diets: a 20% casein diet containing corn oil (CO) or FO, or an 8% casein diet supplemented with cystine plus threonine containing CO or FO. The 8% casein diets reduced urinary protein excretion in nephritic rats without inducing severe growth retardation or fatty liver compared with the basal 20% casein diets. Both the 8% casein diet and the FO diet decreased serum cholesterol, triglyceride and phospholipid levels in nephritic rats, and nonesterified fatty acid levels were decreased by FO feeding. In nephritic animals, hepatic cholesterol synthesis was decreased by the 8% casein diets compared with the 20% casein diets, and tended to be reduced by FO feeding between groups at the same casein levels. No effect of diet was observed on fatty acid synthesis among the nephritic rats. FO administration to the nephritic animals suppressed fecal steroid excretion. While lipoprotein lipase activity was unchanged among the nephritic rats, hepatic triglyceride lipase activity was reduced by either the 8% casein or FO diet. The results suggest that the hypolipidemic action of low casein diets may, at least in part, be due to reduced hepatic cholesterol synthesis and suppressed triglyceride secretion from the liver. They also suggest that the hypolipidemic action of FO may, at least in part, be due to reduced hepatic cholesterol synthesis and decreased fatty acid mobilization from peripheral adipose tissue. PMID- 7869860 TI - Adipose monoacylglycerol:acyl-coenzyme A acyltransferase activity in the white throated sparrow (Zonotrichia albicollis): characterization and function in a migratory bird. AB - Although migrating birds use stored triacylglycerol as their primary fuel for flight, they must retain sufficient stores of omega 6 and omega 3 fatty acids to sustain reproduction after the spring migration. Hepatic monoacylglycerol:acyl coenzyme A acyltransferase (EC 2.3.1.22) (MGAT) activity is associated with physiological periods in which lipolysis and beta-oxidation are prominent, and it may also play a role in the selective retention of certain essential fatty acids. Therefore, we characterized MGAT activity in adipose tissue from the white throated sparrow (Zonotrichia albicollis), a migratory bird. MGAT specific activity from adipose tissue and liver, respectively, was 22.2 +/- 7.27 and 0.79 +/- 0.35 nmol/min/mg of total particulate protein. Activity did not vary seasonally or between male and female birds. Specific activity increased 4.3-fold in the presence of 75 micrograms of phosphatidylcholine and phosphatidylserine (1:1, w/w). MGAT acylated sn-1(3)-monooleoylglycerol, sn-2-monooleylglycerol ether and sn-1(3)-monooleylglycerol ether at 7.5, 5.7 and 1.7%, respectively, of the rate observed with sn-2-monooleoylglycerol. An initial lag phase observed at low concentrations of palmitoyl-CoA was corrected by adding 2 mM MgCl2, Mg(NO3)2 or CaCl2, suggesting a requirement for divalent cations. MGAT acylated sn-2 monolinolenoylglycerol and sn-2-monolinoleoylglycerol in preference to sn-2 monooleoylglycerol. Specificity of MGAT for sn-2-monoacylglycerols and the probable enhanced affinity fo sn-2-monoacylglycerols of specific acyl chains may allow selected omega 6 and omega 3 fatty acids to be retained within the adipocyte, while nonessential fatty acids are released for beta-oxidation in flight muscles. PMID- 7869862 TI - Kinetic study of quenching reactions of singlet oxygen and scavenging reactions of free radicals by alpha-, beta-, gamma- and delta- tocopheramines in ethanol solution and micellar dispersion. AB - Quenching reactions of singlet oxygen and scavenging reactions of free radicals by alpha-, beta-, gamma- and delta-tocopheramines (Toc-amines) were investigated spectrophotometrically in ethanol and Triton X-100 micellar dispersions. The rate constants of quenching of singlet oxygen (kQ) by alpha-, beta-, gamma- and delta Toc-amines increased as the total electron donating capacity of the methyl groups at the aromatic ring increased. A plot of logkQ vs. peak oxidation potential (Ep) was found to be linear and the slope was negative. Similar results were obtained for scavenging of a phenoxyl radical (PhO.). The results suggest that charge transfer plays an important role in these reactions. The kQ values were found to be 1.30-2.57 times as large as kQ for alpha-tocopherol (alpha-Toc). Although alpha-Toc has the highest antioxidant activity among natural tocopherols and related phenols, Toc-amines also can serve as antioxidants. PMID- 7869861 TI - Structural and functional role of lipids in yeast and mycelial forms of Candida albicans. AB - The levels of total lipids, sterols and phospholipids were found to be significantly higher in the mycelial form (log phase) of Candida albicans than in the yeast form. Increased phospholipid levels in the mycelial form were due to higher levels of phosphatidylcholine, phosphatidylserine and phosphatidylinositol. Analyses of fatty acid composition also revealed higher levels of myristic acid (40%) in the yeast form, resulting in higher levels of saturated lipids than in the mycelial form. The changes in the lipid composition were also manifested in altered thermotropic phase behavior as gel-to-liquid crystalline phase transitions were observed at 36 and 27 degrees C for the lipids of the yeast and mycelial forms, respectively. These changes coincided with higher uptake rate, i.e., Km and Vmax values, for the transport of L-proline and with a higher sensitivity of the mycelial form against antifungal drugs. PMID- 7869863 TI - Health system reform: heeding the lessons of history. PMID- 7869864 TI - CME requirements for Maryland medical license renewal. PMID- 7869865 TI - Evaluation and conservative management of women with stress urinary incontinence. AB - Urinary incontinence can be a social and practical problem. A complete evaluation correlating the history, physical examination, and screening studies confirms the syndrome and its significance, leading to the therapeutic management most appropriate for the individual patient. Although long-term cure can be effected by surgery, conservative measures are available and effective depending on the degree of dysfunction and the motivation of the individual patient. PMID- 7869866 TI - Correlation of thyroid histopathology with fine needle aspiration of thyroid nodules: the St. Agnes Hospital experience. AB - Fine needle aspiration (FNA) cytology results were compared with thyroid tissue pathology reports in 44 patients who underwent thyroidectomy. Benign (12) and malignant (10) thyroid cytology interpretations correlated with the final thyroid histopathology. Of 22 thyroid aspirate samples that were considered suspicious or indeterminate, 5 were malignant and 17 were benign. The data obtained support the efficacy of FNA in the evaluation of thyroid nodular disease. PMID- 7869867 TI - Munchausen syndrome: case reports and literature overview. AB - Munchausen syndrome is a subset of factitious disorders with a number of distinguishing characteristics. This article presents three case reports and brief discussions to facilitate recognition. Management techniques are also presented. PMID- 7869868 TI - Pertinent medical intelligence: methadone ingestion in children. PMID- 7869869 TI - Vignette of medical history: the Trimbles of Baltimore. PMID- 7869870 TI - Geriatrics for the clinician. Assessment of caregiver stress. PMID- 7869871 TI - Imaging case of the month. Demonstration of malignant pleural effusion by bone scan. PMID- 7869872 TI - A perspective on the handling of duplicate and redundant publications. PMID- 7869873 TI - Osteoarthritis of the knee: an interdisciplinary perspective. PMID- 7869874 TI - Pathomechanics of knee osteoarthritis. AB - Osteoarthritis of the knee is not only common, but is also responsible for a significant amount of disability in the aging population. Although the exact etiology of this disease process is not known, osteoarthritis has been well described. The primary site affected by osteoarthritis is the articular cartilage. An understanding of the surrounding anatomy, cartilage structure and function, and the response of cartilage to injury will aid both the clinician and researcher in looking for ways to interrupt or retard the degenerative process of osteoarthritis. PMID- 7869875 TI - Physical disability from knee osteoarthritis: the role of exercise as an intervention. AB - Osteoarthritis (OA) of the knee is a common, nonfatal, chronic condition that causes pain and physical disability in older people. Persons with knee OA report difficulty with activities that require ambulation and transfer from the sitting to the standing position. Physical disability from knee OA is the result of a complex interplay among the severity of disease, pain, comorbid conditions, psychosocial factors, and deficits in physical capacity such as low aerobic work capacity and lower extremity muscle weakness. These deficits in physical capacity may be correctable with exercise training. Short-term studies indicate that persons with knee OA show gains in physical capacity and report less pain and disability with exercise training. However, the long-term effectiveness and safety of exercise in persons with knee OA remains unknown. PMID- 7869876 TI - Knee osteoarthritis and health-related quality of life. AB - This section of the symposium addresses the definition, measurement, and relevance of health-related quality of life (HRQL) to osteoarthritis (OA) of the knee. Emphasis is placed on the multidimensional nature of HRQL and the fact that these measures can be used as either outcome or process variables. Clearly, HRQL has been accepted as an appropriate measure of treatment efficacy (an outcome measure) in most clinical research, augmenting the more traditional measures of morbidity and mortality. However, as this paper demonstrates, HRQL measures constitute important process variables in understanding disability and related concepts that are critical in designing effective therapies for treating knee OA. PMID- 7869877 TI - Osteoarthritis of the knee and associated factors of age and obesity: effects on gait. AB - 1) A majority of people afflicted with osteoarthritis (OA) of the knee are elderly and many have their OA exacerbated by obesity. 2) Healthy older adults exhibit gait patterns that differ from a healthy, younger cohort. These differences include a slower walking velocity, slower cadence, shorter step length, reduced hip and knee range of motion, and greater stride width, vertical oscillation, and lateral sway of the head. 3) Subjects afflicted with knee OA have decreased knee range of motion and knee angular velocity, increased loading rate on the less affected leg, and a compensatory increase in hip angular velocity when compared with age matched healthy subjects. 4) Obesity, which is strongly associated with knee OA, increases rearfoot motion during walking and causes the forefoot to abduct significantly more than in normal weight individuals. PMID- 7869878 TI - Effect of swimming exercise and ethanol on rat liver P450-dependent monooxygenases. AB - The interactive effects of 6 wk of repeated swimming exercise and chronic ethanol consumption (36% of total calories) on the hepatic cytochrome P450-dependent monooxygenase system were studied utilizing four groups of male rats in a 2 x 2 factorial design. The sedentary-control (S/C), sedentary-ethanol (S/E), and swim control (SW/C) groups received the same amount of food that the swim-ethanol (SW/E) group consumed. The swimming groups were trained to swim for 2 h.d-1, 5 d.wk-1. Significant main effects due to ethanol (P < 0.002) and exercise (P < 0.02) were observed for the enhanced cytochrome P450 content and cytochrome P450 reductase activity, respectively. In addition, significant main effects for ethanol (P < 0.001), exercise (P < 0.0001), and significant interaction effects (P < 0.005) on aniline p-hydroxylase activity and significant main effects for ethanol (P < 0.01), exercise (P < 0.01), and interaction effects (P < 0.04) on 7 ethoxycoumarin o-deethylase activity were observed. Because the SW/C treatment had no effect on any of the measured cytochrome P450 activities and the SW/E treatment enhanced P450 activities much more than the S/E treatment, the main effects observed for exercise are accounted for by the alterations produced by combining swimming with the ethanol treatment. Based on these results, repeated exercise combined with ethanol consumption produces a synergistic increase in ethanol-inducible cytochrome P450-dependent activities. PMID- 7869879 TI - Cardiac intracellular regulation: exercise effects on the cAMP system and A kinase. AB - The effects of acute and chronic exercise on 3'5'-adenosine monophosphate (cAMP) concentration, adenylate cyclase activity, cAMP-phosphodiesterase (PDE), and cAMP dependent protein kinase (A-kinase) activity are reviewed. During very mild- to moderate-intensity exercise with durations of up to 1 h, the cAMP concentration within the myocardium is related to the intensity of exercise. At higher intensities or during very long-duration exercise, this does not seem to be the case. The mode of exercise does not seem to be a significant factor in altering cardiac cAMP concentration. Duration is more important than intensity in determining cAMP-PDE activity. Post-exercise increases in cAMP-PDE are very similar in trained animals, independent of duration and intensity of work. These increases are attenuated and less variable as compared with untrained animals. The activity of A-kinase seems to increase with exercise training. The extent of the increase in A-kinase activity is likely dependent on the duration (and perhaps the intensity) of training and is of greater magnitude than the changes in the other enzymes of the cAMP system. PMID- 7869880 TI - Exercise reduces fat selection in female Sprague-Dawley rats. AB - This study investigates the relationship between exercise and dietary macronutrient selection. Female Sprague-Dawley rats (5 months old) were placed on a macronutrient self-selection diet for 15 wk. Three food cups, each containing a separate vitamin and mineral supplemented macronutrient, i.e., fat, carbohydrate, or protein, were placed in the cage. Animals were either sedentary (Sed) or treadmill exercised (Ex) at 20 m.min-1, 60 min.d-1, for 6 d.wk-1. Cumulative daily energy and macronutrient intake were determined during this period. Energy intake was not different between Sed and Ex, 211.4 vs 213.5 kjoules.d-1, respectively. However, macronutrient intake differed with less fat eaten for Ex than Sed (81.5 kjoules and 38% for Ex; 114.0 kjoules and 47% for Sed). Carbohydrate and protein intake did not differ significantly between groups. Fifteen weeks of exercise training decreased dietary fat selection, but daily energy intake was not affected. PMID- 7869881 TI - Adaptive properties of the sensorimotor system. PMID- 7869882 TI - Acquisition and maintenance of the simplest motor skill: investigation of CNS mechanisms. AB - The spinal stretch reflex (SSR), or tendon jerk, is the simplest behavior of the vertebrate nervous system. It is mediated primarily by a wholly spinal, two neuron pathway. Recent studies from several laboratories have shown that primates, human and nonhuman, can gradually increase or decrease the size of the SSR when reward depends on such change. Evidence of this training remains in the spinal cord after all supraspinal influence is removed. Thus, the learning of this simple motor skill changes the spinal cord itself. Comparable spinal plasticity probably plays a role in the acquisition of many complex motor skills. Intracellular physiological and anatomical studies are seeking the location and nature of this spinal cord plasticity. Attention focuses on the most probable sites of change, the group Ia afferent synapse on the alpha motoneuron and the motoneuron itself. Results to date indicate that modifications are present at several places in the spinal cord. Current clinical studies are investigating the use of spinal cord adaptive plasticity as a basis for a new therapeutic approach to spasticity and other forms of abnormal spinal reflex function that result from spinal cord injury, stroke, or other neurological disorders. In the future, understanding of spinal reflex plasticity may lead to development of improved training methods for a variety of motor skills. PMID- 7869883 TI - Alterations in synaptic input to motoneurons during partial spinal cord injury. AB - An acute animal model (dorsal hemisection of the spinal cord in the decerebrate cat preparation) has been developed that closely mimics the spasticity in humans that occurs subsequent to partial spinal cord injury and hemiparetic stroke. In this animal model, there are severe disruptions in the pattern of recruitment and rate modulation of motoneurons. The cellular mechanisms of these deficits are being studied with a combined experimental/computer simulation approach. The initial studies indicate that changes in the intrinsic properties of motoneurons are not important, which means the mechanism for changes in recruitment and rate patterns must reside in an alteration in the organization of the synaptic input to motoneurons. Computer simulation studies of the effects of different synaptic inputs on motoneuron outputs show that inhibitory inputs can, under certain conditions, generate substantial disruptions in recruitment and rate modulation. Recent data indicate that the monoamines noradrenalin and serotonin, which are released by fiber tracts originating in the brainstem, may play an important role in maintaining normal levels of inhibition in spinal circuits. Pharmacological interventions based on the monoamines may provide effective means of reducing the deficits in recruitment and rate modulation. PMID- 7869884 TI - Can the mammalian lumbar spinal cord learn a motor task? AB - Progress toward restoring locomotor function in low thoracic spinal transected cats and the application of similar techniques to patients with spinal cord injury is reviewed. Complete spinal cord transection (T12-T13) in adult cats results in an immediate loss of locomotor function in the hindlimbs. Limited locomotor function returns after several months in cats that have not received specific therapies designed to restore hindlimb stepping. Training transected cats to step on a treadmill for 30 min.d-1 and 5 d.wk-1 greatly improves their stepping ability. The most successful outcome was in cats where training began early, i.e., 1 wk after spinal transection. Cats trained to stand instead of stepping had great difficulty using the hindlimbs for locomotion. These effects were reversible over a 20-month period such that cats unable to step as a result of standing training could be trained to step and, conversely, locomotion in stepping-trained cats could be abolished by standing training. These results indicate that the spinal cord is capable of learning specific motor tasks. It has not been possible to elicit locomotion in patients with clinically complete spinal injuries, but appropriately coordinated EMG activity has been demonstrated in musculature of the legs during assisted locomotion on a treadmill. PMID- 7869885 TI - Human neuromuscular adaptations that accompany changes in activity. AB - Neuromuscular adaptations probably occur at all levels of the motor pathway, following changes in muscular activity. Adaptations have been mostly investigated in muscle fibers after heavy-resistance and endurance training. In strength training the rapid improvement is due to poorly understood neural factors, with muscle fiber hypertrophy occurring rather later; fiber hyperplasia is probably unimportant. In contrast to other mammals, muscle fibers in humans do not readily change from "slow" to "fast" and vice versa, although there may be a period of plasticity in infancy especially responsive to weightbearing. A proportion of the changes in the fibers, following training, is probably brought about by stretch activated mechanisms, in which second messengers express immediate early genes and the latter, in turn, promote the transcription of "muscle" genes; other cellular adaptations occur at the level of mRNA translation. In the spinal cord, adaptations following hemiparesis include a loss of functioning motor units. Impaired motor drive occurs not only in organic brain lesions but also after periods of disuse. In persons with amputations, the peripheral nerve stump undergoes degenerative changes; somatosensory cortical evoked responses, following stimulation of the stump, are diminished. It is possible that both sensory and motor cortical representations are increased for neighboring regions of the body. PMID- 7869886 TI - Sodium bicarbonate ingestion does not improve performance in women cyclists. AB - We hypothesized that oral ingestion of sodium bicarbonate (NaHCO3) would improve performance in seven competitive female cyclists VO2 = 51.6 +/- 4.8 ml.kg-1.min-1 at moderate altitude (2800 m). Two hours before exercise subjects ingested either NaHCO3 (300 mg.kg-1) or NaCl (207 mg.kg-1), both containing equimolar amounts of sodium. The exercise protocol consisted of repeated 1-min intervals at 95% VO2max (277 +/- 38 W) followed by 1 min of recovery at 60 W until exhaustion. Continuous cardiopulmonary physiologic variables and arterialized venous blood gases were measured. Maximum interval ventilation, heart rate, and VO2 did not differ between the two interventions, but pH was significantly higher before and throughout the NaHCO3 trial. pH values for NaHCO3 vs NaCl trials were 7.47 +/- 0.04 vs 7.40 +/- 0.03 prior to exercise and 7.32 +/- 0.08 vs 7.23 +/- 0.04 post exercise (P < 0.01). The number of intervals completed with NaHCO3 (10.0 +/- 0.9) was not different from NaCl (8.4 +/- 0.9). The failure of bicarbonate to enhance performance at moderate altitude may be attributed to our controlling for the amount of sodium ingested. The intravascular volume expansion with NaHCO3 rather than the increase in blood buffer capacity may underlie the previously reported benefit of orally ingested bicarbonate in exercise performance. PMID- 7869887 TI - Assessment of energy expenditure for physical activity using a triaxial accelerometer. AB - A triaxial accelerometer was used to evaluate the relationship between energy expenditure due to physical activity (EEact) and body acceleration during different types of activity. In a laboratory experiment, 11 male subjects performed sedentary activities and walked on a motor driven treadmill (3-7 km.h 1). EEact was calculated from total energy expenditure (EEtot), as measured by indirect calorimetry, and sleeping metabolic rate (SMR): EEact = EEtot--SMR. Body accelerations were measured with a triaxial accelerometer at the low back. Special attention was paid to the analysis of unidirectional and three directional accelerometer output. During sedentary activities a linear relationship between EEact and the sum of the integrals of the absolute value of accelerometer output from all three measurement directions (IAAtot) was found (r = 0.82, P < 0.001, Sy,x = 0.22 W.kg-1). During walking EEact was highly correlated with the integral of absolute accelerometer output in antero-posterior direction (IAAx; r = 0.96, P < 0.001, Sy,x = 0.53 W.kg-1). When all examined activities were included in a regression analysis, a strong linear relationship between EEact and IAAtot was found (r = 0.95, P < 0.001, Sy,x = 0.70 W.kg-1). Using this relationship, EEact during sedentary activities as well as EEact during walking could be estimated with an accuracy of about 15%. Although sedentary activities and walking represent a large part of normal daily physical activity, the validity and usefulness of the triaxial accelerometer--measuring IAAtot--to predict EEact in daily life must be studied under free-living conditions. PMID- 7869888 TI - Caltrac versus calorimeter determination of 24-h energy expenditure in female children and adolescents. AB - The purpose of this study was to determine the validity of the Caltrac accelerometer for estimating 24-h energy expenditure (EE) in children and adolescents. EE for 40 girls (13.0 +/- 1.8 yr) was assessed for 24 h via indirect calorimetry in whole-room calorimeters. EE and activity level were estimated concurrently by two Caltrac accelerometers placed on the subjects at each hip. Significant correlations (P < 0.001) resulted between Caltrac estimates and calorimeter values for 24-h total EE (TEE, r = 0.80), sedentary daily EE (SDEE, r = 0.84), and waking EE (WEE, r = 0.85). Nonetheless, the Caltrac significantly (P < 0.001) underestimated EE in all experimental conditions (TEE: -13.3 +/- 8.6%; SDEE: -6.8 +/- 7.3%; WEE: -30.4 +/- 8.5%). A significant multiple correlation between calorimeter values and a combination of Caltrac activity counts and body weight (R = 0.86, P < 0.001) suggested these variables could be useful for daily EE estimation. Additional analyses indicated that as EE increased, the absolute difference between Caltrac and calorimeter values also increased. The significant correlations between Caltrac and calorimeter values suggest the Caltrac may be useful for assessing daily caloric expenditure for groups of children. PMID- 7869889 TI - Changes in metabolites and tissue water status after focal ischemia in cat brain assessed with localized proton MR spectroscopy. AB - Localized proton spectroscopy was used to monitor changes in metabolism and the biophysical status of tissue water in cat brain induced by occlusion of the middle cerebral artery. Changes in the intensity of N-acetyl-aspartate (NAA), total creatine (tCr), and lactate (Lac) signals in localized volumes of interest in the ischemic hemisphere were quantified relative to the preischemic signal. Changes in the apparent diffusion coefficient (ADC), T1- and T2-relaxation times of water in those volumes were also quantified. Lactate was shown to increase rapidly in the first 0.5-2.0 h of ischemia and stabilized afterwards. The ADC of water started to decrease from 0.64 x 10(-9) m2/s to 0.54 x 10(-9) m2/s in the first minutes following occlusion, as was shown in two cases where ADC was measured with high temporal resolution, and stabilized after approximately 3 h at 0.38 x 10(-9) m2/s (n = 6). NAA and tCr decreased by 35% (P < 0.0001) and 30% (P < 0.005), respectively, in the first 8 h of ischemia in comparison with the preischemic control levels. T1 and T2 gradually increased with 0.3 s (P < 0.0001) and 5.2 ms (P < 0.0001), respectively, during the same time span. PMID- 7869890 TI - Experimental encephalomyelitis modulates inositol and taurine in the spinal cord of Biozzi mice. AB - In this high resolution magnetic resonance spectroscopic study of experimental allergic encephalomyelitis (EAE) and Semliki Forest virus (SFV) infection of the Biozzi AB/H mouse, marked increases in the initially low levels of N-trimethyl compounds in the spinal cord were observed during probable demyelinating episodes. There was also a pronounced and reproducible modulation of the levels of taurine and myo-inositol during acute and again during chronic relapsing EAE. The ratio of N-acetyl-aspartate to creatine in the spinal cord of mice infected with the mutant M9 strain of SFV decreased to approximately 70% of that seen in normal mice. PMID- 7869891 TI - Gradient moment nulling in fast spin echo. AB - The fast spin echo sequence combines data from many echo signals in a Carr Purcell-Meiboom-Gill echo train to form a single image. Much of the signal in the second and later echoes results from the coherent addition of stimulated echo signal components back to the spin echo signal. Because stimulated echoes experience no dephasing effects during the time that they are stored as Mz magnetization, they experience a different gradient first moment than does the spin echo. This leads to flow-related phase differences between different echo components and results in flow voids and ghosting, even when the first moment is nulled for the spin echo signal. A method of gradient moment nulling that correctly compensates both spin echo and stimulated echo components has been developed. The simplest solution involves nulling the first gradient moment at least at the RF pulses and preferably at both the RF pulses and the echoes. Phantom and volunteer studies demonstrate good suppression of flow-related artifacts. PMID- 7869892 TI - q-Space imaging of the brain. AB - q-Space imaging (Callaghan, J. Magn. Reson. 88, 493 (1990)) has been used to obtain mouse brain water displacement profiles. These profiles take the form of a unidirectional incoherent-displacement probability density distribution. Two groups of mice were studied, a normal group and one in which surgery had been performed to reduce the supply of blood to the forebrain. In the normal group the incoherent displacement of water was reduced postmortem. Four of the surgically treated mice yielded displacement profiles that resembled those obtained postmortem; the remaining two were near normal. This study demonstrates the feasibility of in vivo q-space imaging. The displacement profile changes that occur subsequent to an interruption of the forebrain blood supply are consistent with the hyperintensity changes seen in diffusion-weighted imaging. PMID- 7869894 TI - Magnetization transfer, cross-relaxation, and chemical exchange in rotationally immobilized protein gels. AB - Water proton spin-lattice relaxation rates are reported as a function of the magnetic field strength for cross-linked bovine serum albumin samples. The relaxation dispersion profile is analyzed using a relaxation model where the solid components have the magnetic field dependence proportional to v-0.5 which may result from a defect diffusion model with two degrees of freedom. If the cross-linking agent concentration is not sufficiently high, the relaxation dispersion curve may have significant contributions from freely rotating protein. The magnetic field dependence of the relaxation rates studied as a function of the proton mole fraction in the sample show that approximately 30% of the magnetization transfer rate is directly proportional to the proton mole fraction. This contribution is identified with the magnetization transfer from exchange of whole water molecules with buried binding sites on the protein. The second order magnetization transfer rate constant is 388 s-1 assuming unit water spin concentration. The solid component relaxation obeys an Arrhenius activation law, but the overall temperature dependence of the cross-relaxation is complicated by chemical exchange processes which enter with opposite sign. PMID- 7869893 TI - Measurement of vascular volume fraction and blood-tissue permeability constants with a pharmacokinetic model: studies in rat muscle tumors with dynamic Gd-DTPA enhanced MRI. AB - We propose a compartmental model to explain the signal enhancement curves following the bolus injection of Gd-DTPA. The model incorporates vascular volume fraction contribution, and the possibility of having different transport constants between the plasma and extravascular components. A Walker 256 carcinoma grown in rat muscle was used to demonstrate the capability of this model. Several different types of tissues were included in the measurements: normal, quickly enhanced, slowly enhanced, and necrotic tissues. Blood volume and blood-tissue permeability information can be derived from the dynamic contrast-enhanced MRI study employing the proposed model. In the tissue contrast enhancement curve, the initial rising slope after injection is related to the blood volume (or, vascular volume fraction), the maximum enhancement ratio is related to the uptake of tissue, and the decay rate is related to the clearance of tracer from tissue. The measured permeability constant is not the conventional permeability; instead they are contrast agents uptake and clearance rates, which are limited by the blood perfusion. These parameters can be used to characterize different enhancement patterns. PMID- 7869895 TI - Initial feasibility studies using single-shot EPI for the detection of focal liver lesions. AB - Echo planar MR imaging (EPI) has been developed to completely eliminate motion artifacts and is currently being prepared for implementation into clinical MR systems. Thus, the purpose of this study was to evaluate the clinical utility of EPI in the detection of focal liver lesions and to compare EPI with in the detection of focal liver lesions and to compare EPI with contrast-enhanced CT. EPI studies were performed on an experimental 1.0 Tesla whole body system using fat-suppressed single-shot spin echo (SE) and inversion recovery (IR) pulse sequences. A total of 26 liver tumors in 12 patients scheduled for liver resection were prospectively examined and correlated with intraoperative ultrasound, surgery, and pathology as the gold standard. Quantitative analysis of EPI was performed by means of liver signal-to-noise and tumor-liver contrast-to noise calculations. Diagnostic performance compared with contrast-enhanced CT was assessed by means of ROC analysis. Lesion-liver contrast was highest with EPI SE at a TE-time of 70 ms and this technique showed best lesion detectability as measured by area under curve (AUC) values. Among EPI techniques, the IR sequence with an inversion time of 300 ms to null the liver signal showed high lesion liver contrast but all four reviewers reported problems assessing liver anatomy. Improved EPI techniques may prove useful for screening of focal liver lesions. PMID- 7869896 TI - A dynamically adaptive imaging algorithm for wavelet-encoded MRI. AB - A new adaptive algorithm based on wavelet-encoded MRI is presented for application in dynamic imaging. This algorithm is adaptive because the strategy for updating image data in the dynamic series of images is determined by the processing of the most recently acquired data. The spatially selective multi resolution properties of the wavelet transform are exploited to selectively update only those regions of the field of view where change is actually occurring. A theoretical imaging model is presented to motivate use of the adaptive algorithm, and simulation results using both artificial and experimental wavelet-encoded data are presented. PMID- 7869897 TI - Theory of NMR signal behavior in magnetically inhomogeneous tissues: the static dephasing regime. AB - This paper is devoted to a theory of the NMR signal behavior in biological tissues in the presence of static magnetic field inhomogeneities. We have developed an approach that analytically describes the NMR signal in the static dephasing regime where diffusion phenomena may be ignored. This approach has been applied to evaluate the NMR signal in the presence of a blood vessel network (with an application to functional imaging), bone marrow (for two specific trabecular structures, asymmetrical and columnar) and a ferrite contrast agent. All investigated systems have some common behavior. If the echo time TE is less than a known characteristic time tc for a given system, then the signal decays exponentially with an argument which depends quadratically on TE. This is equivalent to an R2* relaxation rate which is a linear function of TE. In the opposite case, when TE is greater than tc, the NMR signal follows a simple exponential decay and the relaxation rate does not depend on the echo time. For this time interval, R2* is a linear function of a) volume fraction sigma occupied by the field-creating objects, b) magnetic field Bo or just the objects' magnetic moment for ferrite particles, and c) susceptibility difference delta chi between the objects and the medium. PMID- 7869898 TI - Detection of propan-1,2-diol in neonatal brain by in vivo proton magnetic resonance spectroscopy. AB - Cerebral in vivo proton magnetic resonance spectroscopy of 13 newborn infants displaying seizures and receiving phenobarbitone, in one case supplemented by phenytoin, showed signals from propan-1,2-diol (the injection vehicle for both these anticonvulsants). Subsequent in vitro spectroscopy of cerebro spinal fluid (CSF) from one of these infants also showed signals from this substance. The estimated in vivo propan-1,2-diol concentration (approximately 3 mM) was less than that measured in the CSF sample (14.4 mM). These observations suggest that propan-1,2-diol may accumulate in cerebral tissue and misidentification of its signals in both in vivo and in vitro proton spectra may confuse diagnoses of metabolic or other disorders. PMID- 7869899 TI - A gradient scheme suitable for localized shimming and in vivo 1H/31P STEAM and ISIS NMR spectroscopy. AB - A gradient scheme is presented which may be used for STEAM or ISIS localization. One application of the scheme is to perform single-shot STEAM shimming prior to data acquisition with STEAM and ISIS, using identical gradient amplitudes and durations. Using conventional STEAM to shim for ISIS can produce line-shape distortions induced by different eddy currents in the two sequences; with this gradient scheme the problem is minimized. Line-shape improvements of STEAM and ISIS localized data obtained after volume localized shimming with the proposed STEAM sequence are demonstrated. The localization performance of the STEAM and ISIS sequences are demonstrated on phantoms and in vivo for 1H and 31P metabolites. PMID- 7869900 TI - Minimization of dead-periods in MRI pulse sequences for imaging oblique planes. AB - With the advent of breath-hold MR cardiac imaging techniques, the minimization of TR and TE for oblique planes has become a critical issue. The slew rates and maximum currents of gradient amplifiers limit the minimum possible TR and TE by adding dead-periods to the pulse sequences. We propose a method of designing gradient waveforms that will be applied to the amplifiers instead of the slice, readout, and phase encoding waveforms. Because this method ensures that the gradient amplifiers will always switch at their maximum slew rate, it results in the minimum possible dead-period for given imaging parameters and scan plane position. A GRASS pulse sequence has been designed and ultra-short TR and TE values have been obtained with standard gradient amplifiers and coils. For some oblique slices, we have achieved shorter TR and TE values than those for nonoblique slices. PMID- 7869901 TI - A strategy for sampling on a sphere applied to 3D selective RF pulse design. AB - Conventional constant angular velocity sampling of the surface of a sphere results in a higher sampling density near the two poles relative to the equatorial region. More samples, and hence longer sampling time, are required to achieve a given sampling density in the equatorial region when compared with uniform sampling. This paper presents a simple expression for a continuous sample path through a nearly uniform distribution of points on the surface of a sphere. Sampling of concentric spherical shells in k-space with the new strategy is used to design 3D selective inversion and spin-echo pulses. These new 3D selective pulses have been implemented and verified experimentally. PMID- 7869902 TI - The theory of shielded loop resonators. AB - We present a mathematical model for shielded loop resonators. The model implies equivalent circuits for coaxial as well as flat Faraday shielded resonators under both balanced and unbalanced termination conditions. Expressions for impedance derived from the model are shown to agree well with observation using two test experimental resonators in a variety of experimental conditions. PMID- 7869903 TI - A new method for proton detection of H2(17)O with potential applications for functional MRI. AB - A method is presented for the sensitive detection of minute amounts of H2(17)O. The method is based on the increase of the T2 of the water protons following an irradiation of the 17O resonance frequency, due to the partial or full decoupling of the 1H-17O spin-spin interaction. It is demonstrated that when 17O concentrations are low, full decoupling is achieved, and at short echo times the increase in the amplitude of the proton echo signal is proportional to the 17O content of the sample. The potential of the method for indirect 17O imaging is substantiated by a simple one dimensional projection of cylindrical phantoms containing various 17O concentrations. Using interleaved sequences with and without 17O decoupling, errors due to time dependent effects are minimized. PMID- 7869904 TI - A MRI bolus tagging method for observing helical flow in the descending aorta. AB - We present a MRI bolus tagging method for exploring the helical nature of blood flow in the aorta. Two image series are collected, the first to quantify longitudinal flow (coronal/sagittal imaging plane-transverse saturation plane), the second to measure rotational flow (transverse imaging plane-coronal/sagittal saturation plane). The experimental protocol has been established in healthy adult volunteers and children with normal vasculature. Our results permit immediate visualization of the unique nature of helical flow in each volunteer. We demonstrate evidence of rapid helical twist, no helical twist, and reversal of twist. PMID- 7869905 TI - Rigorous and careful identification of compounds in 31P NMR spectra. PMID- 7869906 TI - Parathyroid hormone-induced retraction of MC3T3-E1 osteoblastic cells is attenuated by the calpain inhibitor N-Ac-Leu-Leu-norleucinal. AB - Parathyroid hormone (PTH) binding to its osteoblastic receptors stimulates cytoplasmic retraction within minutes. We hypothesized that the calpains (calcium activated papain-like enzymes) contribute to PTH-induced osteoblastic retraction by catalyzing regulatory hydrolysis of cytoskeletal structural proteins or enzymes important in cytokinesis. N-Ac-Leu-Leu-norleucinal (ALLN), a reversible calpain inhibitor, was tested for its ability to inhibit PTH-induced retraction in murine MC3T3-E1 osteoblastic cells. ALLN inhibited PTH-induced retraction for 30 minutes in cells cultured on polystyrene cultureware or gelatin-coated glass cover slips, supporting the hypothesis that PTH-induced activation of the calpains contributes to short-term changes in MC3T3-E1 cell shape. Inhibition of PTH-induced retraction occurred on two substrata, suggesting that interactions between the extracellular matrix and cell surface proteins are not the sole determinants of morphology. Intracellular events, such as hydrolysis of focal adherens junction proteins on the cytoplasmic face of the plasma membrane, may contribute to PTH-induced retraction. PMID- 7869907 TI - Interleukin-6 stimulates gluconeogenesis in primary cultures of rat hepatocytes. AB - Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 have been shown to stimulate the synthesis of acute-phase proteins; however, few studies have examined the effect of these cytokines on gluconeogenesis. We investigated the effects of these cytokines on gluconeogenesis in primary cultures of rat hepatocytes. Incubation of hepatocytes for 24 hours with TNF-alpha or IL-1 alpha did not affect gluconeogenesis. Hepatocytes incubated with 100 pmol/L and 1 nmol/L IL-6 had a dose-dependent increase (P < .05) in gluconeogenesis (2.6 +/- 0.1 and 3.2 +/- 0.1 pmol/10(6) cells/min, respectively) as compared with controls (2.0 +/- 0.1). PMID- 7869908 TI - Serum sialic acid as an indicator of change in coronary artery disease. AB - We measured serum levels of total sialic acid (TSA) by an enzymatic method in 74 men who completed the St Thomas' Atherosclerosis Regression Study (STARS). Coronary artery disease (CAD) was assessed as the change (delta) in mean absolute width of coronary segments (MAWS) over 3 years by a computerized technique. Delta TSA was significantly correlated with delta MAWS (r = -.50, P < .001) after adjusting for age, blood pressure, smoking status, and plasma low-density lipoprotein (LDL) cholesterol. The relative risk of progression of CAD for a delta TSA exceeding 10 mg/dL as compared with a delta TSA not exceeding 10 mg/dL was 4.6 (95% confidence interval, 2.4 to 8.7). We conclude that serial measurement of serum TSA levels may be a useful indicator of the progression of CAD. PMID- 7869909 TI - Short- and long-term effect of oral salbutamol on growth hormone secretion in prepubertal asthmatic children. AB - Salbutamol, a beta 2-adrenergic agonist, is being extensively used in Venezuela as a brochodilator in the treatment of asthma in children. Previous reports have shown oral salbutamol either to inhibit or not to affect growth hormone (GH) secretion. We evaluated the effect of oral salbutamol (0.1 mg/kg every 6 hours for 3 months) on GH secretion in eight prepubertal short children with mild asthma. Levels of GH during sleep (samples taken every 30 minutes from 9 PM to 6 AM) and after GH-releasing hormone ([GHRH] 1 microgram/kg intravenously [IV]) were measured before, at 24 hours, and at 3 months of salbutamol treatment. Overnight integrated concentrations of GH and peak GH levels following GHRH diminished significantly after 24 hours of salbutamol therapy (from 4.5 +/- 1.3 to 3.4 +/- 0.8 micrograms/L and from 46.6 +/- 47.3 to 16.2 +/- 7.9 micrograms/L, respectively, P < .05). However, GH levels after 3 months of salbutamol were not different from basal levels (4.5 +/- 1.3 v 5.1 +/- 5.1 +/- 2.9 micrograms/L during the overnight studies and 46.6 +/- 47.3 v 37.8 +/- 30.4 micrograms/L after GHRH). Our data suggest an inhibition of both spontaneous and stimulated GH secretion following short-term oral salbutamol ingestion, but this suppressive effect is not maintained with its long-term use. PMID- 7869910 TI - Effect of age on the response of blood lipids, body composition, and aerobic power to physical conditioning and deconditioning. AB - The influence of age on the response of plasma lipids, body composition, and cardiovascular performance to physical training and detraining was studied in 12 older and 12 young adult male cyclists. The athletes were first examined at the peak of their seasonal preparation and then again 2 months after its suspension. Sedentary males matched for age, weight, and height comprised the respective control groups. During training, body fat mass (BFM) was significantly lower and maximum oxygen consumption (VO2max) higher in both groups of cyclists as compared with controls. No differences in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo) B, apo A-II, and fibrinogen were found. During the same phase, triglycerides (TG) and the LDL-C to high density lipoprotein cholesterol (HDL-C) ratio were significantly lower and apo A I, HDL-C, HDL3-C, and the apo A-I/apo B ratio were significantly higher in the athletes than in their corresponding sedentary controls. After physical deconditioning, BFM increased and VO2max decreased significantly in both groups of athletes. TG, very-low-density lipoprotein cholesterol (VLDL-C), and fibrinogen increased in young athletes while the LDL-C/HDL-C ratio increased, and apo A-I, HDL-C, HDL2-C, and HDL3-C decreased significantly in both young and older athletes. Thus, an aerobic training program induced an antiatherogenic lipoprotein profile and beneficial modifications in body composition and aerobic power in both older and younger subjects; a 2-month interruption in the program changed these parameters unfavorably in both groups. Age does not seem to influence significantly the plasma lipid response to physical deconditioning. PMID- 7869911 TI - Pyruvate inhibits clofibrate-induced hepatic peroxisomal proliferation and free radical production in rats. AB - In an effort to identify the effects of the 3-carbon compound pyruvate on free radical production, we measured hepatic total peroxisomal beta-oxidation and catalase activity and the production of lipofuscin-like products in male Sprague Dawley rats consuming an adequate diet supplemented with pyruvate, vitamin E, or the peroxisome proliferator and free radical enhancer clofibrate for 22 days (n = 5 in each group). Clofibrate feeding induced hepatomegaly, a fivefold increase in total peroxisomal beta-oxidation activity, and a threefold increase in hepatic lipofuscin-like products (P < .05). Pyruvate but not vitamin E inhibited the increase in liver size by 70% (P < .05). Both pyruvate and vitamin E completely inhibited clofibrate-induced increases in lipofuscin-like products (P < .05). Pyruvate but not clofibrate or vitamin E increased plasma concentrations of the nitric oxide metabolites nitrite and nitrate (P < .05). We conclude that with clofibrate-induced peroxisomal proliferation and free radical production, pyruvate will inhibit peroxisomal proliferation and free radical production, inhibit free radical-induced lipid peroxidation, and enhance metabolism of nitric oxide. PMID- 7869912 TI - Rate of glucose entry into hepatic uridine diphosphoglucose by the direct pathway in fasted and fed states in normal humans. AB - We used the glucuronate (GlcUA) probe technique to measure the rate of glucose entry into hepatic uridine diphosphoglucose (UDP-glc) by the direct pathway, to quantify the rate of appearance (Ra) of hepatic UDP-glc, and to calculate hepatic glucose cycling in vivo in normal humans. The direct pathway contribution to UDP glc as determined by the ratio of [1-d1]-GlcUA to plasma [LD1]-glucose enrichments was minor (15% to 20%) in normal men after an overnight fast. After 9 hours of refeeding with intravenous (IV) glucose or an oral liquid formula meal each at a rate of 7 mg carbohydrate/kg/min, the direct pathway increased to 66.3% +/- 6.7% and 61.6% +/- 6.0% (mean +/- SE), respectively. Plasma glucose concentrations remained below 7.8 mmol/L and could not account for most of the variability in direct pathway contribution. The dilution of labeled [L-D1] galactose in excreted acetaminophen-GlcUA was used to measure Ra UDP-glc, on the assumption that labeled galactose passes through the liver during its assimilation. Ra UDP-glc was 1.1 +/- 0.1 mg/kg/min after an overnight fast and increased to 2.0 +/- 0.1 with i.v. glucose and 2.6 +/- 0.2 with the oral liquid mixed meal. By combining the fractional glucose contribution with the Ra of hepatic UDP-glc, the rate of direct glucose entry into hepatic UDP-glc was 0.2 mg/kg/min (fasted) and increased to 1.3 to 1.6 (fed). This represented approximately 18% to 21% of systemic glucose disposal or 19% to 23% of the administered carbohydrate load during i.v. or oral refeeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869913 TI - Beta-adrenergic stimulation and abdominal subcutaneous fat blood flow in lean, obese, and reduced-obese subjects. AB - The present study was designed to investigate whether the beta-adrenergically mediated blood flow response of abdominal subcutaneous adipose tissue (per unit adipose tissue weight) was altered in obesity and to study the effect of weight reduction on this response. Body composition (underwater weighing) and fat blood flow were determined in a group of lean (n = 9; % body fat, 11.6 +/- 3.9) and obese (n = 9; % body fat, 28.3 +/- 1.8) subjects. In seven obese subjects, measurements were also performed after a 4-week period of weight reduction induced by a very-low calorie diet (% body fat after diet 23.4 +/- 3.3). After an overnight fast, abdominal subcutaneous fat blood flow was determined by the 133xenon washout technique during a 30-minute period of supine rest and during 30 minute periods of infusion of the beta-agonist isoprenaline (ISO) with and without simultaneous infusion of the beta 1-blocker atenolol (AT). Basal abdominal fat blood flow was significantly higher in lean as compared with obese subjects, whereas weight reduction significantly increased basal fat blood flow (obese v reduced-obese, P < .05). There was a significant increase in abdominal fat blood flow as a result of ISO infusion in lean and obese subjects before and after weight reduction. During ISO+AT infusion, abdominal fat blood flow was still significantly increased as compared with control values in lean and obese subjects. The increase in blood flow during ISO was significantly higher in lean subjects than in obese subjects, whereas the ISO+AT-induced blood flow response was comparable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869914 TI - The effects of long-term aerobic exercise and energy restriction on protein synthesis. AB - Long-term aerobic exercise and energy intake regulate body composition in a complex manner. To study the combined effects of exercise and energy restriction on muscle mass, we measured skeletal and cardiac muscle protein synthesis after 28 days of two levels of energy restriction with or without daily running-wheel exercise in female rats. Protein synthesis was measured as 3H-Phe incorporation 10 minutes' postbolus of a flooding pulse injection. The two exercise plus energy restriction groups had greater skeletal muscle and cardiac muscle mass compared with their food-matched groups. Cardiac, gastrocnemius, and soleus muscle protein synthetic rates were proportional to their muscle masses. Exercise-induced energy deficits preserved cardiac and soleus mass to a greater extent than gastrocnemius mass, whereas the effects of energy restriction were similar in all three muscles. These findings suggest that energy intake and exercise have independent effects on the regulation of muscle mass and protein synthesis. PMID- 7869916 TI - Effect of cyclodextrin on plasma lipids and cholesterol metabolism in the rat. AB - beta-Cyclodextrin (beta-CD) is a bile acid and sterol sequestrant produced by enzymatic modification of starch; this product has the potential to decrease plasma cholesterol. In contrast to the sequestrants having resin- or saponin-like properties, beta-CD is rapidly broken down by the large intestine microflora. beta-CD effects on cecal fermentations and lipid metabolism were thus investigated in rats adapted to semipurified diets containing 0%, 2.5%, or 5% beta-CD. In rats fed beta-CD diets, there was an enlargement of the cecum together with a dramatic increase in the cecal concentration of propionic acid (even with the 2.5% level, in moderately acidic pH conditions). Propionic acid produced in the cecum was readily absorbed and entirely taken up by the liver, whereas there was no significant acetic acid uptake. Dietary beta-CD was highly effective in enhancing bile acid entry into to the cecum: the cecal bile acids pool was 2.2 and 3.6-fold enlarged in rats fed the 2.5% and 5% beta-CD diets, respectively. The solubility percentage of bile acids decreased to approximately 25% in rats fed the beta-CD diets (v 51% in controls); the cecal concentration of soluble bile acids was thus relatively low in these animals. The fecal excretion of steroids was strongly enhanced by beta-CD, and bile acids excretion was practically proportional to the dietary beta-CD level. There was a net lipid lowering effect of beta-CD, even at the 2.5% level. The effect was more pronounced on triglycerides than on cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869915 TI - Thyroid hormone action: effect of triiodothyronine on mitochondrial adenine nucleotide translocase in vivo and in vitro. AB - Adenine nucleotide translocase (AdNT) levels were measured as the exchange of extramitochondrial against intramitochondrial adenosine diphosphate (ADP) in liver, spleen, and testes mitochondria isolated from normal and hypothyroid rats using the "back-exchange" and atractyloside-stop method of Pfaff and Klingenberg. The results provide confirmation of previous reports that mitochondria from hypothyroid rats show a markedly diminished AdNT activity, which is restored to normal levels within 72 hours by intraperitoneal injection of 10 to 20 micrograms triiodothyronine (T3)/100 g body weight. The latter dose was found in dose response studies to result in maximal stimulation of AdNT in liver mitochondria. Qualitatively similar results on AdNT activity were obtained in liver mitochondria within 30 to 60 minutes following intravenous injection into hypothyroid rats of a more physiological dose of T3 (40 ng/100 g body weight). AdNT in mitochondria isolated from spleen and testes (organs that do not exhibit a calorigenic response after administration of thyroid hormone to the whole animal) failed to respond to thyroidectomy and to administration of T3. More recently, we have observed that in vitro replacement of T3 also stimulates AdNT activity in hypothyroid liver mitochondria. The enzyme adenosine triphosphate (ATP) synthase was examined as another possible candidate for direct hormonal stimulation of mitochondria. Simultaneous determinations on the same rats after intraperitoneal injection of T3 (20 micrograms/100 g body weight) showed little or no effect on ATP synthase until after 37 to 85 hours, whereas enhanced activity of the translocator was regularly observed at 17 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869917 TI - Hyperuricemia in patients with hyperthyroidism due to Graves' disease. AB - The effects of hyperthyroidism on uric acid metabolism were investigated. First, the serum uric acid level was measured in 92 patients with hyperthyroidism due to Graves' disease, eight patients with subacute thyroiditis, six patients with hypothyroidism, and 70 sex- and age-matched controls. Second, the correlation between serum thyroxine (T4) and serum uric acid was obtained in hyperthyroid Graves' disease patients before and during antithyroid drug therapy. Finally, uric acid clearance (CUA) was determined in untreated patients with hyperthyroidism due to Graves' disease. Serum uric acid was significantly elevated in patients with hyperthyroidism, and the elevation correlated well with serum T4 before treatment as a group and during treatment in each patient. A significant elevation of serum uric acid was not present in patients with a transient mild thyrotoxicosis due to subacute thyroiditis. Serum uric acid was significantly decreased in patients with hypothyroidism. Renal excretion of uric acid clearly increased in hyperthyroid patients, and CUA also increased. The increase in CUA corresponded to the increase in renal plasma flow (RPF), which was measured by p-aminohippuric acid clearance. The fractional excretion of uric acid as determined by CUA/glomerular filtration rate (GFR) was similar and within the normal range in hyperthyroid patients and normal controls. A significant inverse correlation between CUA and serum uric acid concentration was present in hyperthyroid patients as in normal controls, indicating that the renal handling of uric acid in the tubule affected uric acid excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869918 TI - A comparison between the effects of gemfibrozil and simvastatin on insulin sensitivity in patients with non-insulin-dependent diabetes mellitus and hyperlipoproteinemia. AB - In a double-blind, randomized crossover study, 29 patients with non-insulin dependent diabetes mellitus (NIDDM) and hyperlipoproteinemia were treated with gemfibrozil (1,200 mg/d) or simvastatin (10 mg/d) for 4 months. After gemfibrozil treatment, the insulin concentration was increased during the major part of the intravenous glucose tolerance test (IVGTT) and during the hyperinsulinemic euglycemic clamp. Similar but less pronounced elevations were caused by simvastatin. Insulin sensitivity decreased by 27% and 28% during gemfibrozil and simvastatin treatment, respectively. Low-density lipoprotein (LDL) cholesterol was decreased with simvastatin treatment by 24%. The LDL cholesterol level was not changed by gemfibrozil, but very-low-density lipoprotein (VLDL) cholesterol was reduced by 40%. The VLDL triglyceride concentration was reduced to a significantly greater extent by gemfibrozil. After gemfibrozil treatment, lipoprotein(a) [Lp(a)] was decreased by 24%, and the plasma free fatty acid (FFA) concentration was increased by 20% and skeletal muscle lipoprotein lipase activity (LPLA) by 37%. Although simvastatin more effectively decreased LDL cholesterol levels and the LDL to high-density lipoprotein (HDL) ratio, it cannot be claimed unreservedly that this drug is necessarily preferable in NIDDM patients. Gemfibrozil improved triglyceride removal and decreased VLDL concentrations, with qualitative changes in LDL. The apparent effects on insulin sensitivity are difficult to evaluate and need further study. PMID- 7869919 TI - Meal frequency influences circulating hormone levels but not lipogenesis rates in humans. AB - To determine whether human lipogenesis is influenced by the frequency of meal consumption, 12 subjects were divided into two groups and fed isocaloric nutritionally adequate liquid diets over 3 days, either as three larger diurnal (n = 6) or as six small, evenly spaced (n = 6) meals per day. On day 2 (08:00 h) of each diet period, 0.7 g deuterium (D) oxide/kg body water was administered and blood was collected every 4 hours over 48 hours for measurement of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) levels. At each time point, the incorporation of D into plasma triglyceride fatty acid (TG-FA) was also determined by isotope ratio mass spectrometry after TG-FA extraction and combustion/reduction. Insulin and GIP levels were elevated over daytime periods in subjects fed three versus six meals per day. Contribution of de novo synthesis to total TG-FA production was not significantly different for days 2 and 3 in subjects consuming three (6.56% +/- 1.32% and 6.64% +/- 2.08%, respectively) and six (7.67% +/- 2.29% and 7.88% +/- 1.46%, respectively) meals per day. Net TG-FA synthesis rates over days 2 and 3 were 1.47 +/- 0.33 and 1.55 +/- 0.53 g/d, respectively, for subjects fed three meals per day, and 1.64 +/- 0.47 and 1.69 +/ 0.30 g/d for subjects fed six meals per day. These findings suggest that consuming fewer but larger daily meals is not accompanied by increases in TG-FA synthesis, despite the observation of hormonal peaks. PMID- 7869921 TI - Evidence to suggest nitric oxide is an interstitial regulator of Leydig cell steroidogenesis. AB - Recent studies have suggested that nitric oxide (NO) may function as both an intracellular and intercellular signal that affects neural and immunological activity, vascular tone, platelet adhesion, and production of some hormones. Arginine analogs such as NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L arginine methyl ester (L-NAME) act to inhibit the intracellular formation of NO and have been used to study the effects of decreased NO formation on physiological systems. A single in vivo study has suggested that a similar analog, NG-nitro-L-arginine, increases serum testosterone (T), but the organ site and mechanism of action were not investigated. The present study was performed to investigate the effects of NO synthase inhibitors on Leydig cell function. L-NMMA and L-NAME, but not the inactive enantiomer (D-NMMA), increased both basal and human chorionic gonadotropin (hCG)-stimulated T production while decreasing guanosine 3':5'-cyclic monophosphate (cGMP). There was no effect on either adenosine 3':5'-cyclic monophosphate (cAMP) accumulation or specific hCG binding. These results suggest that NO formation, which is inhibited by L-NMMA and L-NAME, is important in the regulation of Leydig cell T production by interstitial cells of the testis, and that changes in cGMP levels might be involved in this process. PMID- 7869920 TI - In vivo effects of hyperinsulinemia on lipogenic enzymes and glucose transporter expression in rat liver and adipose tissues. AB - Chronic hyperinsulinemia with maintenance of euglycemia was imposed on normal rats for 4 days. In white adipose tissue, hyperinsulinemia resulted in a twofold increase in GLUT4 protein and mRNA and a sixfold to 15-fold increase in fatty acid synthase (FAS) and acetyl coenzyme A (CoA) carboxylase (ACC) activity, respectively. Lipogenic enzyme mRNA was also markedly increased (20- to 30-fold). This was specific for white adipose tissue and was not observed in brown adipose tissue. In the liver, hyperinsulinemia was accompanied by a threefold increase in glucokinase (GK) activity and mRNA and by a threefold to fivefold increase in lipogenic enzyme activities and mRNA. In agreement with the changes in lipogenic activities, lipogenesis was markedly increased in white adipose tissue and liver of hyperinsulinemic rats. The data strongly suggest that in the rat, insulin is a driving force leading to increased lipid synthesis in liver and white adipose tissue. PMID- 7869922 TI - Increased concentrations of proteins Gi1 and Gi2 in adipocytes from aged rats alter the sensitivity of adenylyl cyclase to inhibitory and stimulatory agonists. AB - We used a series of antipeptide antisera to estimate the relative amounts of G proteins in adipocytes from young lean versus aged obese Sprague-Dawley rats. Western blots were analyzed using antisera that recognize (1) the alpha-subunits of Gi1 and Gi2 (serum SG1), (2) the alpha-subunit of Gi3 (serum I3B) (3) two forms of the alpha-subunit of Gs (serum CS1), and (4) forms of the beta-subunits common to all the G proteins (serum BN2). Adipocyte membranes from aged rats contained approximately fivefold to sixfold more alpha i1 and alpha i2 than those from young rats, but almost equal amounts of alpha i3. Membranes from aged rats had a modestly higher (50%) amount of a 43-kd and normal amounts of a 47-kd form of alpha s. Membranes from old rats also had approximately a threefold higher amount of beta-subunits, consistent with increased concentrations of some of the G proteins but not others. Finally, the functional consequences of these differences in G proteins was investigated by measuring the effect of N6 phenylisopropyl adenosine ([PIA] an A1-adenosine receptor agonist) and isoproterenol on adenylyl cyclase activity. Adenylyl cyclase was more sensitive to inhibition by PIA in membranes from old rats than from young rats, but was less sensitive to stimulation by isoproterenol, suggesting that the differences we observed are functionally active G proteins. These findings may account for the altered sensitivity of adipocytes from old rats to antilipolytic and lipolytic hormones. PMID- 7869923 TI - Metabolic and hormonal responses to adrenoceptor antagonists in exercising rats. AB - alpha- and beta-adrenoceptors play a key role in the regulation of nutrient supply to working muscles during exercise. To assess their influence in the regulation of substrate utilization, rats were studied during alpha- or beta adrenoceptor blockade. Energy metabolism was studied by means of indirect calorimetry before, during, and after moderate swimming exercise. Blood samples were taken for the determination of nutrient and hormone concentrations. In addition, central venous blood samples were withdrawn for determination of blood gases, pH, and total hemoglobin concentration (c/Hb). alpha- and beta adrenoceptor blockade decreased the rates of energy expenditure (EE) and fat oxidation (fat-ox) during and after swimming in comparison to swimming without adrenoceptor blockade. The oxidation of carbohydrates (CHO-ox) was increased in both cases. alpha-Blockade prevented the exercise-induced increase in blood glucose, plasma free fatty acids (FFA) were not affected, and plasma insulin, norepinephrine (NOR), epinephrine (EPI), and lactate were markedly increased. beta-adrenoceptor blockade prevented the exercise-induced increases in blood glucose and FFA. EPI increased slightly more than and NOR less than in the control experiment. The exercise-induced decrease in insulin was more pronounced after beta-blockade. alpha-Blockade caused a less pronounced decrease in venous oxygen saturation (SO2) and tension (PO2) than in the control experiment. The exercise-induced increase in carbon dioxide tension (PCO2) was almost absent. After beta-blockade, venous SO2 and PO2 decreased more and PCO2 increased more than in the control experiment. It is concluded that both alpha and beta-blockade restrict the rate of EE during exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869924 TI - The contribution of proinsulin and des-31,32 proinsulin to the hyperinsulinemia of diabetic and nondiabetic cirrhotic patients. AB - We used specific, monoclonal antibody-based, two-site immunoradiometric assays to test the hypothesis that serum levels of proinsulin and des-31,32 proinsulin would be increased in cirrhosis, particularly in those with overt diabetes. A 75 g oral glucose tolerance test was performed after an overnight fast in eight cirrhotic patients with diabetes (fasting blood glucose, 7.8 +/- 2.2 [SE] mmol/L), seven nondiabetic cirrhotic patients, and eight normal control subjects. Fasting serum immunoreactive insulin levels were approximately six times higher in cirrhotics than in controls, but were not different between diabetic and nondiabetic cirrhotic patients. After oral glucose, the incremental area under the serum insulin concentration curve was 3,475 +/- 1,009 pmol.L-1.h in nondiabetic cirrhotic patients, significantly higher than in controls (761 +/- 48, P < .001) or diabetic cirrhotic patients (881 +/- 186, P < .05). Fasting serum proinsulin levels in diabetic cirrhotic patients (24.0 +/- 5.7 pmol/L) were higher than in controls (2.3 +/- .05, P < .001) or nondiabetic cirrhotic patients (4.4 +/- 0.8, P < .005). Fasting serum levels of des-31,32 proinsulin were also much higher in diabetic cirrhotic patients than in nondiabetic cirrhotic patients or controls (P < .02 and P < .005, respectively). Fasting proinsulin plus des 31,32 proinsulin constituted 12.5% +/- 1.4% of serum immunoreactive insulin in diabetic cirrhotics, higher than in nondiabetic cirrhotics (3.7% +/- 0.5%, P < .001) and normal controls (7.8% +/- 1.5%, P = .035).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869926 TI - Effects of captopril on glucose transport activity in skeletal muscle of obese Zucker rats. AB - This study tested whether the angiotensin-converting enzyme (ACE) inhibitor captopril can modify the glucose transport system in insulin-resistant skeletal muscle. Obese Zucker (fa/fa) rats (approximately 300 g)--a model of insulin resistance--were administered by gavage either a single dose (50 mg/kg body weight) or repeated doses (50 mg/kg/d for 14 consecutive days) of captopril. Corresponding groups of age-matched, vehicle-treated lean (Fa/-) littermates (approximately 170 g) were also studied. Glucose transport activity in the epitrochlearis muscle was assessed by in vitro 2-deoxyglucose (2-DG) uptake. The increase in 2-DG uptake due to insulin (2 mU/mL) in muscles from vehicle-treated obese rats was less than 50% (P < .05) of the increase observed in muscles from lean rats. Short-term captopril treatment improved insulin-stimulable 2-DG uptake in muscles from obese rats by 46% (P < .05), and this enhanced insulin action due to captopril was completely abolished by pretreatment with the bradykinin antagonist HOE 140 (100 micrograms/kg). Long-term treatment with captopril produced a 60% improvement in insulin-stimulated 2-DG uptake (P < .05). Contraction-stimulated 2-DG uptake was significantly impaired (-31%, P < .05) in the obese rat, but was not altered by long-term captopril treatment. These findings indicate that both short- and long-term treatments with captopril significantly improve insulin-stimulated glucose transport activity in skeletal muscle of the obese Zucker rat, and that this improvement involves bradykinin metabolism. These data therefore support the hypothesis that captopril-induced improvements in glucose disposal result in part from an enhancement of the skeletal muscle glucose transport system. PMID- 7869925 TI - Glucose transport, phosphorylation, and utilization in isolated porcine pancreatic islets. AB - Porcine islets have been proposed as a donor source for human transplantation, mainly because of both structural and biological similarities of porcine and human insulin. However, the in vitro function of these islets is poorly characterized. In the present study, we first examined insulin release in response to glucose in static incubation experiments. Increasing glucose concentrations up to 8.3 mmol/L stimulated insulin release; however, this elevation was only twofold, and a paradoxical decline was observed at glucose concentrations higher than 8.3 mmol/L. In cultured porcine islets, a greater insulin secretion may be elicited by agents that increase intracellular cyclic adenosine monophosphate (cAMP) levels. To investigate the possible reasons for the porcine islet low response to glucose in vitro, we then evaluated in parallel experiments glucose transport, phosphorylation, and utilization. Glucose transport studies (using 3-O-methyl glucose uptake at 15 degrees C for 15 seconds) indicated the presence of both a high-affinity (Km, 1.2 +/- 0.6 mmol/L) and a low-affinity (Km, 11.8 +/- 1.9 nmol/L, n = 5) component. Glucose phosphorylation, evaluated by measuring the rate of glucose-6-phosphate formation in a fluorimetric assay, indicated that glucokinase activity had a maximum (Vmax) of 7.97 +/- 0.94 nmol/microgram DNA/h and a Km of 8.3 +/- 0.9 mmol/L (mean +/- SE, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869928 TI - The role of dexfenfluramine in the regulation of energy balance. Introduction. PMID- 7869927 TI - Differential effects of high-fat diets varying in fatty acid composition on the efficiency of lean and fat tissue deposition during weight recovery after low food intake. AB - The energetics of body weight recovery after low food intake was examined in the rat during refeeding for 2 weeks with isocaloric amounts of high-fat (HF) diets providing 50% of energy as either lard, coconut oil, olive oil, safflower oil, menhaden fish oil, or a mixture of all these fat types. The results indicate that for both body fat and protein, the efficiency of deposition was dependent on the dietary fat type. The most striking differences were found (1) between diets rich in n-3 and n-6 polyunsaturated fatty acids (PUFA), with the diet high in fish oil resulting in a greater body fat deposition and lower protein gain than the diet high in safflower oil; and (2) between diets rich in long-chain (LCT) and medium chain triglycerides (MCT), with the diet high in lard resulting in a greater gain in both body fat and protein than the diet high in coconut oil. Furthermore, the diet high in olive oil (a monounsaturated fat) and the mixed-fat diet (containing all fat types) were found to be similar to the fish oil diet in that the efficiency of fat deposition was greater (and that of protein gain lower) than with the diet high in safflower oil. Neither the efficiency of fat gain nor that of protein gain were found to correlate with fasting plasma insulin, the insulin to glucose ratio, or plasma lipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869929 TI - The Role of Dexfenfluramine in the Regulation of Energy Balance. Proceedings of a satellite symposium of the European Congress on Obesity. Ulm, Germany, June 10, 1993. PMID- 7869930 TI - An epidemiologic study of food consumption habits in Germany. AB - Food consumption habits were studied in subgroups of subjects in the German Nutrition Survey (Nationale Verzehrstudie [NVS]) on the basis of body weight. Our study was performed in an 18- to 88-year-old representative subgroup of 2,006 noninstitutionalized volunteers with no significant pathology (known as the Verbundstudie, Ernahrungserhebung, and Risikofaktorenanalytik [VERA] subgroup). Using the German Food Code, food and nutrient intakes were calculated from 7-day dietary records. A stratification analysis was used to determine significant differences in food consumption habits of overweight subjects in comparison to normal-weight subjects. The results showed an increase in the prevalence of overweight (body mass index [BMI], 25 to 30) with age, from 15% in the group aged 18 to 24 years to 50% in the group aged more than 55 years. The prevalence of severe overweight (BMI, 30 to 40) increased from 3% to 17% in the same age groups, whereas morbid obesity (BMI, > 40) was found in only 0.4% of the study population. The calculated daily energy intake showed only a very weak correlation with BMI, probably because individual energy requirements and expenditures were not taken into account. However, differences were found between BMI subgroups in terms of the types of food consumed: a high BMI was associated with a higher consumption of meat and meat products but a lower consumption of milk and dairy products and bread and other cereal-based foods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869931 TI - Food consumption habits in Germany--the clinician's point of view. AB - Findings of the Nationale Verzehrstudie and Verbundstudie, Ernahrungserhebung und Risikofaktorenanalytik studies are discussed in light of their clinical significance. Obesity increases the statistical risk of developing a number of diseases, of which the most important are cardiovascular morbidity and mortality. Obesity causes insulin resistance and plays a part in the development of the metabolic syndrome. The Verbundstudie, Ernahrungserhebung und Risikofaktorenanalytik survey shows that in the mid-1980s roughly one third of the German population was overweight. However, criteria for defining the overweight condition are variable. Overall data in Germany are comparable to those of several other population surveys, but regional increases are observed. Analysis of dietary intakes shows a marked deviation from recommended nutritional standards, especially in the distribution of total caloric intake as carbohydrate (42.8%) and fat (38.4%). Almost 9% of the population derived more than 20% of their energy intake from snacks. The data cannot provide a full explanation as to why people become fat. This may be due to the well-known problem of underrating and underreporting intakes, particularly by obese subjects. PMID- 7869932 TI - Limitations in the assessment of dietary energy intake by self-report. AB - Development of the doubly-labeled water method has made it possible to test the validity of dietary intake instruments for the measurement of energy intake. Comparisons of measured energy expenditure with energy intake from either weighed or estimated dietary records against energy expenditure have indicated that obese subjects, female endurance athletes, and adolescents underestimate habitual and actual energy intake. Individual underestimates of 50% are not uncommon. Even in non-obese adults, where bias is minimal, the standard deviation for individual errors in energy intake approaches 20%. Two investigations of the validity of self-reported dietary records for measuring change in dietary intake also indicate large underestimates of the actual change. Because of bias and imprecision, self-reported energy intakes should be interpreted with caution unless independent methods of assessing their validity are included in the experimental design. PMID- 7869933 TI - Metabolic abnormalities linked to obesity: effects of dexfenfluramine in the corpulent rat. AB - The JCR:LA-corpulent rat is a useful experimental model for the obese-diabetic dyslipidemic syndrome that mimics the human condition and exhibits spontaneous development of atherosclerosis and myocardial lesions. A 30-day treatment of 6 month-old rats with dexfenfluramine 1, 2.5, and 5 mg per kilogram decreased body weight through loss of adipose tissue mass. The effect is caused primarily by the ability of dexfenfluramine to reduce food intake. The maximum depression of food intake and greatest weight loss is seen during the first 10 days of treatment in this experimental model; thereafter, body weight stabilizes. However, during this period, there is a marked decrease in serum concentrations of triglycerides, cholesterol, and insulin. Corpulent male rats were also treated from 6 to 37 weeks of age with dexfenfluramine 2.5 mg/kg. This also produces a sustained decrease in body weight and a decrease in circulating insulin concentrations. Preliminary evidence demonstrates a substantial decrease in the incidence of necrotic myocardial lesions produced by ischemic events. This study establishes that dexfenfluramine treatment can decrease the severity of associated risk factors for cardiovascular disease, namely obesity, diabetes, and dyslipidemias. Furthermore, we report the first evidence that long-term treatment with dexfenfluramine can largely prevent the occurrence of myocardial lesions and end stage cardiovascular disease in this animal model prone to atherosclerosis. PMID- 7869934 TI - Effect of dexfenfluramine on fat mass distribution in a high-fat rat model. AB - It has been shown that in contrast to peripheral fat, visceral fat is an important risk factor for cardiovascular diseases and diabetes. In this study, we investigated whether dexfenfluramine (dF), a compound known to decrease body fat, affects fat mass differentially in various regions of the body. We used a moderately obese rat model fed a high-fat diet (40% fat). After 35 days on the diet, rats were divided into three groups: a dF-treated group ([D]2.5 mg/kg intraperitoneally twice daily), a pair-fed group (Cp), and a control group (C) fed ad libitum. C and Cp rats were injected with saline. After 4 weeks of treatment, body fat, fat cell morphology, and metabolism were determined in subcutaneous (inguinal [ING]) and visceral (retroperitoneal [RET] and mesenteric [MES]) fat tissues. Food intake in D and Cp rats was similar, and was lower than in the C group. In comparison to Cp and C rats, D rats had lower body weight and body fat, smaller ING and RET fat pad weights, and smaller fat cell size in all depots. No significant differences were observed in fat mobilization between groups; however, fat accumulation tended to be lower in D rats. These data suggest that dF has an effect on adipose tissue independent of its effect on food intake. However, this effect seems to occur without regional specificity. PMID- 7869935 TI - Serotonin and dietary fat intake: effects of dexfenfluramine. AB - Traditionally, serotonin (5-HT) has been most commonly linked with carbohydrate (CHO) intake. However, in recent years it has been demonstrated that serotoninergic drugs such as dexfenfluramine also reduce energy intake and reverse body weight gain in rats exposed to weight-increasing high-fat diets. Dexfenfluramine is also effective in decreasing food intake and body weight gain of rats that gain weight on a high-fat cafeteria diet. The basic science studies indicate that serotoninergic activity--induced by dexfenfluramine--can act as a sufficient stimulus for the reduction of fat consumption. High-fat diets do not appear to impede the suppressive effect of dexfenfluramine on food intake. In human studies with dexfenfluramine, it has often been the case that the fat content of test foods has been held constant--with only protein and CHO allowed to vary. These studies therefore cannot display any direct effect on fat. However, when food choice is not limited by experimental constraints, a significant reduction of fat intake by dexfenfluramine has been demonstrated in obese patients. In other experimental studies, dexfenfluramine has suppressed fat intake to a greater extent than other macronutrients when free selection of foods has been permitted. Taken together, these studies demonstrate that dexfenfluramine is effective at reducing energy intake with a diet high in fat and may under certain conditions cause a selective avoidance of high-fat foods. PMID- 7869936 TI - Regulation of nutrient metabolism and energy expenditure. AB - The requisites for energy expenditure are covered mainly by two major substrates, glucose and free fatty acids (FFA). Their regulation and metabolism differ. After carbohydrate ingestion, glucose is rapidly oxidized or stored in muscles and liver. There is a constant alternance between glucose storage as glycogen after meals and glycogen mobilization in the postabsorptive state when plasma glucose has returned to the basal state. Impairment of this alternance, in particular when glycogen stores are not being used, may lead to glucose intolerance and insulin resistance. Ingestion of lipids is not followed by an immediate increase in lipid oxidation, but FFA are stored as triglycerides in different tissues. Lipolysis occurs in the fasting state from tissue triglycerides and favors lipid oxidation. Lipid oxidation is typically increased in obesity. The preferential use of FFA from triglyceride stores for energy expenditure in obesity is responsible for the decrease in glucose mobilization from glycogen stores. This leads to a negative feedback of muscle and liver glycogen on glycogen synthase activity and consequently on glucose storage. It results in glucose intolerance after carbohydrate ingestion. Diabetes develops in obesity, usually after a long period of glucose intolerance, when glycemia does not return to the basal state. In obesity, glucose intolerance and insulin resistance can be prevented, or if already existing, can be decreased by stimulating glycogen mobilization by exercise, thermogenesis-stimulating drugs, and weight loss, which reduces fat stores and decreases lipid oxidation. PMID- 7869937 TI - Effects of dexfenfluramine on resting metabolic rate and thermogenesis in premenopausal obese women during therapeutic weight reduction. AB - To investigate whether a serotoninergic drug such as dexfenfluramine (dF) may have some beneficial effects on energy expenditure (EE) during therapeutic weight reduction, a 3-month study was conducted in a double-blind, placebo-controlled trial. Thirty-two obese, premenopausal women received either dF or placebo (P) in addition to a very-low-calorie diet (VLCD) prescription. All patients started- when hospitalized at the metabolic ward--with a 500-kcal regimen and fulfilled the 3-month trial on a +/- 760-kcal protein-sparing modified fast. Although not statistically significant, women receiving dF lost more weight (16.0 +/- 1.4 v 12.8 +/- 1.3 kg, P = .111) over the 3-month study period. Resting metabolic rate (RMR) decreased significantly by 5% in the dF group (4.79 to 4.53 kJ/min) and by 9% in the P group (5.09 to 4.63 kJ/min). When expressed per kilogram body weight, RMR significantly increased from 0.050 to 0.057 kJ/min/kg in the dF group (P < .001), versus 0.053 to 0.056 in the P group (NS). When expressed per kilogram fat free mass (FFM), RMR remained stable in the dF group, whereas it significantly decreased in the P group (P = .024). No significant differences could be found between groups. Glucose-induced thermogenesis (GIT), expressed as percent increase above RMR, did not show significant differences between groups. When expressed per kilogram body weight, mean GIT increased in the dF group from 0.14% to 0.16% above RMR, with a significant decrease from 0.15% to 0.13% in the P group. Only during the first hour did GIT per kilogram body weight significantly (P = .038) increase in the dF group during the outpatient period (between day 16 and day 90). These results show that a serotoninergic drug seems capable of limiting the weight reduction-associated decrease in RMR and dietary-induced thermogenesis (DIT), certainly when expressed on a per-kilogram-weight basis. PMID- 7869938 TI - Eating habits of obese patients in The Netherlands: a comparison between various subgroups and the general Dutch population. AB - It is still uncertain whether subgroups of obese subjects demonstrate different eating patterns. The aim of this report is to compare data on dietary intake obtained by different methods (dietary history and dietary diary) in several groups of obese patients in which the effects of weight-reducing agents were investigated. In our first and our second study, the latter part of an international multicenter study, we investigated the weight-reducing potential of lipase inhibition, a novel concept in the treatment of obesity, in healthy moderately obese subjects. In the third study, part of a national multicenter study, we investigated the effect of a serotoninergic drug (dexfenfluramine) on eating habits in moderately obese people who considered themselves snackers. Eating habits of the third group seem to be different from those of the other two groups in both men and women. These patients have a greater total energy intake due to a greater carbohydrate and fat intake. In our second study, little difference is found when results obtained by dietary history are compared with those obtained by dietary diaries. Our comparisons indicate that groups of obese patients with different patterns of eating behavior may exist and that obese snackers have a significantly greater energy intake. Therefore, various therapeutic strategies for weight reduction may be useful for patients with different types of eating behaviors. Furthermore, the methods by which data on dietary intake are obtained seem to show comparable results and therefore at least suggest accuracy. PMID- 7869939 TI - Chronobiometric identification of disorders of hunger sensation in essential obesity: therapeutic effects of dexfenfluramine. AB - In human beings, hunger is a proprioceptive signal that shows intraday (circadian components) and within-day (ultradian components) recursivity. Both periodic components can be investigated by chronobiometric procedures by combining the Cosinor method with spectral analysis. A 24-hour profile of hunger sensation (HS) can be plotted on a 1-to-10 scale of intensity using self-rated scores performed every half-hour of the day. Circadian and ultradian components were studied in 60 patients affected by essential obesity (20 men and 40 women; mean age, 38.4 years; mean body weight, 101 kg) before and after treatment with dexfenfluramine (Isomeride; Servier, Orleans, France) 15 mg orally twice daily, for 30 days. The control group consisted of 30 clinically healthy subjects (15 men and 15 women; mean age, 37.5 years; mean body weight, 69 kg). Chronobiometric analysis shows three patterns in obese patients, which suggests that HS may be normal (eurectic obesity), exaggerated (hyperrectic obesity), or diminished (hyporectic obesity). After dexfenfluramine administration, HS was showed a substantial decrease in the daily mean level. The spectrum of resolution in circadian and ultradian components was found to be maintained in eurectic obesity and partially readjusted in hyperrectic and hyporectic obesities. This demonstrates that dexfenfluramine acts not only as an anorectic but also as a chronizer by interfering with the recursive components of HS. The anorectic and chronizing effects suggest that dexfenfluramine is a "chronoanorectic drug" that interacts with the chronobiologic properties of the serotoninergic system. PMID- 7869940 TI - Effects of dexfenfluramine on free fatty acid turnover and oxidation in obese patients with type 2 diabetes mellitus. AB - To test the potential effects of dexfenfluramine (dF) on enhancing free fatty acid (FFA) turnover and oxidation rates, 11 obese female non-insulin-dependent diabetes mellitus (NIDDM) outpatients (age, 52.5 +/- 1.5 years; weight, 81.3 +/- 3.2 kg; height, 158 +/- 3.04 cm; body mass index, 32.4 +/- 0.7 kg/m2) received a primed-constant infusion of 1-14C-palmitate. The waist to hip ratio (WHR) was 0.91 +/- 0.04. Fat body mass and lean body mass, assessed by dual-energy x-ray densitometry, were 32.0 +/- 1.5 and 49.30 +/- 2.67 kg, respectively. All patients had an average hemoglobin A1 of 6.3% +/- 0.3% in the month preceding the study and had not received oral hypoglycemic agents. Gas exchange was measured both basally and during a ventilated-hood system, indirect-calorimetry session. The protocol was a randomized, placebo-controlled, single-blind design. Subjects received dF 30 mg acutely (n = 6) or a placebo (n = 5). A dose of dF 15 mg twice daily or placebo was then administered over 15 days (chronic). To obtain serum peak level of the drug, dF was administered 2 hours before starting palmitate infusion. A free diet was allowed throughout the study, and the group treated with dF lost approximately 0.5 kg body weight. Acute and chronic dF administration resulted in a significant increase in FFA oxidation, expressed as a percentage of the dose of radiocarbon (respectively, 11.47% +/- 0.46% v 9.50% +/- 0.46% [P < .01] and 12.06% +/- 0.71% v 9.88% +/- 0.62% [P < .01]). FFA turnover rate was higher after both acute and chronic dF administration (respectively, 10.71 +/- 2.18 v 7.79 +/- 1.48 mumol/kg/min [P < .05] and 11.92 +/ 2.74 v 8.43 +/- 1.86 mumol/kg/min [P < .05]). Serum FFA concentration during both acute and chronic dF administration increased, but not significantly. Mean serum glucose level decreased after acute dF from 114.3 +/- 8.6 to 86.5 +/- 5.1 mg/dL (P < .001) and after chronic dF from 120.3 +/- 7.3 to 89.8 +/- 5.8 mg/dL (P < .001). Serum insulin was not affected by dF administration. In conclusion, oral acute and chronic dF administration increase FFA turnover and oxidation rates in NIDDM obese patients. This may play an important role in weight reduction. In addition, dF shows a weight-independent effect on glucose metabolism, reducing serum glucose levels without acting on insulin secretion. PMID- 7869941 TI - Modeling the relational complexities of symptoms. AB - Realization of the value of reliable codified medical data is growing at a rapid rate. Symptom data in particular have been shown to be useful in decision analysis and in the determination of patient outcomes. Electronic medical record systems are emerging, and attempts are underway to define the structure and content of these systems to support the storage of all medical data. The underlying models upon which these systems are being built continue to be strengthened by a deeper understanding of the complex information they are to store. This report analyzes symptoms as they might be recorded in free text notes and presents a high-level conceptual data model representation of this domain. PMID- 7869942 TI - A model for structured data entry based on explicit descriptional knowledge. AB - Clinical narratives in patient records are usually recorded in free text, limiting the use of this information for research, quality assessment, and decision support. This study focuses on the capture of clinical narratives in a structured format by supporting physicans with structured data entry (SDE). We analyzed and made explicit which requirements SDE should meet to be acceptable for the physician on the one hand, and generate unambiguous patient data on the other. Starting from these requirements, we found that in order to support SDE, the knowledge on which it is based needs to be made explicit: we refer to this knowledge as descriptional knowledge. We articulate the nature of this knowledge, and propose a model in which it can be formally represented. The model allows the construction of specific knowledge bases, each representing the knowledge needed to support SDE within a circumscribed domain. Data entry is made possible through a general entry program, of which the behavior is determined by a combination of user input and the content of the applicable domain knowledge base. We clarify how descriptional knowledge is represented, modeled, and used for data entry to achieve SDE, which meets the proposed requirements. PMID- 7869943 TI - The PEN & PAD medical record model: development of a nursing record for hospital based care of the elderly. AB - The PEN & PAD Medical Record model describes a framework for an information model, designed to meet the requirements of an electronic medical record. This model has been successfully tested in a computer-based record system for General Practitioners as part of the PEN & PAD (GP) Project. Experiences of using the model for developing computer-based nursing records are reported. Results show that there are some problems with directly applying the model to the nursing domain. Whilst the main purpose of the nursing record is to document and communicate a patient's care, it has several other, possibly incompatible, roles. Furthermore, the structure and content of the information contained within the nursing record is heavily influenced by the need for the nursing profession to visibly demonstrate the philosophical frameworks underlying their work. By providing new insights into the professional background of nursing records, this work had highlighted the need for nurses to clarify and make explicit their uses of information, and also provided them with some tools to assist in this task. PMID- 7869944 TI - Patient records: from single events to elements for health planning. AB - Data collected in patient records are not only the kernel of a ward information system, but also the groundwork for planning and evaluating services in health care. The aim of this study was to analyze the problem of aggregate data generation starting from separate items in patient records. After describing the different uses of patient record data, we outline the process which generates aggregates data starting from individual records. This process leads to the definition of the "view on aggregation" as an intermediate step between patient records and aggregate data. A simplified schema is presented based on the Entity Relationship model representing a conceptual model of the integration of aggregate data and patient record items. Finally, the role is discussed of automation in this process and the perspectives for its implementation. PMID- 7869945 TI - A unified approach to the design of clinical reporting systems. AB - Computer-based Clinical Reporting Systems (CRS) for diagnostic departments that use structured data entry have a number of functional and structural affinities suggesting that a common software architecture for CRS may be defined. Such an architecture should allow easy expandability and reusability of a CRS. We report the development methodology and the architecture of SISCOPE, a CRS originally designed for gastrointestinal endoscopy that is expandable and reusable. Its main components are a patient database, a knowledge base, a reports base, and screen and reporting engines. The knowledge base contains the description of the controlled vocabulary and all the information necessary to control the menu system, and is easily accessed and modified with a conventional text editor. The structure of the controlled vocabulary is formally presented as an entity relationship diagram. The screen engine drives a dynamic user interface and the reporting engine automatically creates a medical report; both engines operate by following a set of rules and the information contained in the knowledge base. Clinical experience has shown this architecture to be highly flexible and to allow frequent modifications of both the vocabulary and the menu system. This structure provided increased collaboration among development teams, insulating the domain expert from the details of the database, and enabling him to modify the system as necessary and to test the changes immediately. The system has also been reused in several different domains. PMID- 7869946 TI - Terminology of the thalamus and its representation in a part-whole relation. AB - In stereotaxic neurosurgery, a variety of operative procedures focus on thalamic targets. The nomenclature of thalamic nuclei and subnuclei, however, has not yet been settled. In clinical and laboratory environments several terminologies coexist. This is an obstacle to both communication and a better understanding of recent electrophysiological findings. In the late 1980s, the application of new histochemical and immunohistochemical methods led to a deeper insight into existing correlationships between the nomenclatures. As a uniform terminology of the thalamus is still lacking, we created a knowledge-based system (THALAMUS) which gives a comprehensible survey about the most important terminologies. The different nomenclatures are related to each other by organizing them in a component-integral relation. This part-whole relation contains both the knowledge on the subdivisions of the thalamus as well as the knowledge on the correlations between the various nomenclatures. PMID- 7869947 TI - An information system for epidemiology based on a computer-based medical record. AB - A new way is presented to build an information system addressed to problems in epidemiology. Based on our analysis of current and future requirements, a system is proposed which allows for collection, organization and distribution of data within a computer network. In this application, two broad communities of users physicians and epidemiologists-can be identified, each with their own perspectives and goals. The different requirements of each community lead us to a client-service centered architecture which provides the functionality requirements of the two groups. The resulting physician workstation provides help for recording and querying medical information about patients and from a pharmacological database. All information is classified and coded in order to be retrieved for pharmaco-economic studies. The service center receives information from physician workstations and permits organizations that are in charge of statistical studies to work with "real" data recorded during patient encounters. This leads to a new approach in epidemiology. Studies can be carried out with a more efficient data acquisition. For modelling the information system, we use an object-oriented approach. We have observed that the object-oriented representation, particularly its concepts of generalization, aggregation and encapsulation, are very usable for our problem. PMID- 7869948 TI - Application of capture-recapture methods for disease monitoring: potential effects of imperfect record linkage. AB - Capture-recapture methods are increasingly employed to correct for underascertainment of cases in disease monitoring. Routine systems of disease monitoring, such as morbidity registries, are often prone to specific threats of validity, such as in imperfect diagnoses or imperfect record linkage. A quantitative assessment is given of the performance of the two-source capture recapture method for disease monitoring in the presence of imperfect record linkage. The capture-recapture approach can eliminate underestimation of the number of eligible cases, which is typical for most disease monitoring systems, under certain conditions, including independence of sources of case ascertainment and perfect record linkage. Correction for underestimation remains less than perfect, however, in the case of false-positive matches, whereas application of capture-recapture methods leads to overestimation of case numbers in the presence of false-negative matches. A simple correction procedure to overcome potential overestimation by false-negative matches is outlined. PMID- 7869949 TI - Computerized databases for emergency care: what impact on patient care? AB - A field-based evaluation is conducted of a Clinical Computerized Information System (CCIS). Following training, the use of the CCIS database, word processing and other programs by thirteen full-time practicing emergency physicians in two urban emergency departments of a University-associated teaching hospital was studied over a one-year period. A tracking program automatically logged frequency and duration of use by the physicians, and user satisfaction was assessed by a reliable and validated questionnaire instrument. Based on utilization data and verbal reports of these physicians, CCIS database searching was not only found to be easy-to-learn but was readily accessible during emergency shifts. Individual physicians were found to perform an average of 3.5 searches per month lasting a mean search time of 8 min. Positive notes about the CCIS system included ease-of use, accuracy of data, accessibility of system, and value of output while negative perceptions included a lack of integration with other systems, a lack of system completeness, and a high subscription cost. It was suggested that a less costly telephone link to a high-volume Centre would be desirable in actual implementation of the system. PMID- 7869951 TI - MEDUSA: a fuzzy expert system for medical diagnosis of acute abdominal pain. AB - Even today, the diagnosis of acute abdominal pain represents a serious clinical problem. The medical knowledge in this field is characterized by uncertainty, imprecision and vagueness. This situation lends itself especially to be solved by the application of fuzzy logic. A fuzzy logic-based expert system for diagnostic decision support is presented (MEDUSA). The representation and application of uncertain and imprecise knowledge is realized by fuzzy sets and fuzzy relations. The hybrid concept of the system enables the integration of rule-based, heuristic and case-based reasoning on the basis of imprecise information. The central idea of the integration is to use case-based reasoning for the management of special cases, and rule-based reasoning for the representation of normal cases. The heuristic principle is ideally suited for making uncertain, hypothetical inferences on the basis of fuzzy data and fuzzy relations. PMID- 7869950 TI - A compartmental model for simulation of IGF-I kinetics and metabolism. AB - A compartmental model for the simulation of in-vivo insulin-like growth factor one (IGF-I) kinetics and metabolism is presented. The model is based on the concept that IGF binding proteins (IGFBPs) act as a reservoir for IGF-I in plasma, thereby restricting its access to the extravascular space. The model is divided into two subsystems; a binding model for IGF-I and IGFBP, and an IGF-I clearance model, which includes the binding of IGF-I to IGF-I receptors. The non linear differential equations describing the model are based on the law of mass action. Given the steady state condition, the linearized form of the model, describing tracer kinetics of IGF-I and IGFBPs is developed. It is demonstrated that using the available data, it is possible to assign values to the model parameters, thereby allowing simulation of the model to obtain information not accessible by direct observation. PMID- 7869952 TI - Patient registration and treatment allocation in multicenter clinical trials using a FAX-OCR system. AB - This article describes the design and results of implementation of an automated patient registration and treatment allocation system (RETAS) used in multicenter clinical trials. RETAS was developed using a FAX-OCR system by which handwritten Japanese and English characters, as well as numericals and forms with check boxes, are sent from participating institutions by Fax, processed using an optical character reader, and then transmitted to a host computer at a statistical center. Based on the facsimile data, RETAS can automatically review eligibility, collect patient identification data and provide a randomized treatment allocation. RETAS permits uninterrupted, unattended operation at a statistical center, 24 hours a day, 7 days a week. Therefore, it drastically decreases the workload of personnel at the statistical center needed to support central telephone registration coverage. Consequently, staff members are free to focus on patient registration, treatment allocation, and follow-up of patients. The treatment allocation procedure in this system is based on Pocock and Simon's minimization method combined with Zelen's method for institution balancing. By this system it was possible to balance treatment numbers for each level of various prognostic factors over an entire trial and, at the same time, balance the allocation of treatments within an institution. The system currently supports the protocol of a clinical trial for Adjuvant Chemo-Endocrine Therapy for Breast Cancer in West Japan. PMID- 7869953 TI - Mixed Bayesian networks: a mixture of Gaussian distributions. AB - Mixed Bayesian networks are probabilistic models associated with a graphical representation, where the graph is directed and the random variables are discrete or continuous. We propose a comprehensive method for estimating the density functions of continuous variables, using a graph structure and a set of samples. The principle of the method is to learn the shape of densities from a sample of continuous variables. The densities are approximated by a mixture of Gaussian distributions. The estimation algorithm is a stochastic version of the Expectation Maximization algorithm (Stochastic EM algorithm). The inference algorithm corresponding to our model is a variant of junction three method, adapted to our specific case. The approach is illustrated by a simulated example from the domain of pharmacokinetics. Tests show that the true distributions seem sufficiently fitted for practical application. PMID- 7869954 TI - Expression of fimbriae and host response in Branhamella catarrhalis respiratory infections. AB - Sputum during the acute exacerbation of chronic respiratory diseases were observed under the electron microscope, to determine the in vivo expression of surface structures of Branhamella catarrhalis (B. catarrhalis), the polymorphonuclear neutrophil (PMN) response to B. catarrhalis infections, and the composition of sputum. It was found that during infection fimbriae are expressed in B. catarrhalis. However, there were sparsely to densely fimbriated bacteria in each sputum sample. The length of the fimbriae were from 50 to 76 nm. In the sparsely fimbriated B. catarrhalis, external to the cell wall, a thin, granular, electron-dense layer was observed. Due to the presence of fimbriae, this layer was not seen in densely fimbriated B. catarrhalis. Blebs were also found in B. catarrhalis. PMNs were found to phagocytose both B. catarrhalis and debris. Evidence was found that debris were formed mainly by the destruction of PMNs. Bacteria as well as debris were phagocytosed by PMNs. PMID- 7869955 TI - Enterotoxigenicity, hemolytic activity and antibiotic resistance of Aeromonas spp. isolated from freshwater prawn marketed in Dhaka, Bangladesh. AB - Aeromonas spp. were isolated from gills, swimmerets, eggs, stomachs and ventral muscles of freshwater prawns (Macrobrachium malcolmsonii) available in the local fish market of Dhaka, Bangladesh. The density of Aeromonas spp. on these different body parts of the prawn samples ranged from 1.1 +/- 0.2 x 10(4) to 1.5 +/- 0.16 x 10(7) cfu per gram. The viable counts of aeromonads, fecal coliforms (FC) and Escherichia coli gradually increased in prawn samples when stored at 4 C. At -20 C, the viable counts gradually decreased and became zero on the 12th day of storage. The isolation of A. sobria (56%) was more frequent than that of A. hydrophila (31%) and A. caviae (13%). In the rabbit ileal loop (RIL) model, fluid accumulation induced by live cultures and cell-free culture filtrates of 11 strains ranged from 0.5 to 1.5 and 0.5 to 1.7 ml/cm of gut, respectively. Of 11 enterotoxigenic strains, 7 were A. sobria and 4 were A. hydrophila. Enterotoxigenicity correlated with hemolytic activity on blood agar. All enterotoxigenic strains were uniformly sensitive to chloramphenicol and gentamicin and resistant to novobiocin and vancomycin. Isolation of enterotoxigenic and antibiotic-resistant Aeromonas from these prawn samples indicates possible public health problems for their handlers as well for raw prawn consumers. PMID- 7869956 TI - CD8+ T lymphocytes are the major cell population involved in the early gamma interferon response and resistance to acute primary Toxoplasma gondii infection in mice. AB - Gamma interferon (IFN-gamma) is known to be a major mediator influencing host defense against Toxoplasma (T.) gondii. To evaluate lymphocyte populations involved in this cytokine-mediated early resistance to T. gondii, the effects of in vivo administration of monoclonal antibodies (MAbs) against T-cell subsets and anti-asialo GM1 antibody on the course of infection and IFN-gamma response were investigated in mice infected acutely with this parasitic protozoan. A single injection of anti-CD8 MAb on day -1 or day 4 severely exacerbated the infection, in accordance with a marked suppression of endogenous IFN-gamma production. Moreover, the administration of anti-IFN-gamma MAb on day 0 but not later than day 4 resulted in a total abrogation of resistance to T. gondii, suggesting that endogenous IFN-gamma produced during the first several days of infection is critical for the generation of antitoxoplasmal resistance in mice. In contrast, no significant increase in mortality was observed when injected with either anti CD4 MAb or anti-asialo GM1 antibody on day -1, while these antibodies reduced significantly the ability of mice to produce IFN-gamma. Indeed, simultaneous depletion of CD4+ and CD8+ cells had no greater suppressive effect on host defense and endogenous IFN-gamma production than depletion of CD8+ cells alone. Together, these results suggest that CD8+ T cells play a central role for resolution of acute toxoplasmosis by participating in endogenous IFN-gamma production. The possible role of early produced IFN-gamma in the development of protective immune response to T. gondii is also discussed. PMID- 7869957 TI - Use of the recombinant 38-kDa antigen of Mycobacterium tuberculosis as an immunogen for specific antisera production. AB - The Mycobacterium tuberculosis 38-kDa protein antigen is one of the secreted immunodominant antigens showing high immunogenicity at B-cell and T-cell levels. Although monoclonal antibodies to this antigen have been produced, specific polyclonal antisera is required for standardization of specific immunodiagnostic assays. This protein has been overexpressed and purified from recombinant Escherichia coli using an inducible vector system. During each stage of expression and purification, the recombinant protein was used to immunize mice and rabbits by several methods: 1) as overexpressed protein present as inclusion bodies in recombinant E. coli; 2) embedded in a polyacrylamide gel; 3) fixed to a solid-phase nitrocellulose membrane and 4) emulsified with an adjuvant. All strategies yielded specific antisera as determined by enzyme-linked immunosorbent assay (ELISA) and immunoblot analyses. The results obtained, both quantitative (ELISA) and qualitative (immunoblot) demonstrate that the purified recombinant antigen retains its antigenicity and immunogenicity throughout the various steps in the process of expression and purification and serves as a potent antigen for production of specific antisera to be used in immunoassays. PMID- 7869958 TI - In vivo-like antigenic surface properties of Staphylococcus aureus from bovine mastitis induced upon growth in milk whey. AB - Antigenic surface properties of Staphylococcus aureus strains grown in milk whey were compared with TSB-grown bacteria using immuno-gold electron microscopy. It is shown that colloidal gold (CG) particles coated with polyclonal antibody raised against Staphylococcus aureus surface antigen expressed in vivo bound to the surface of S. aureus strain F1440 grown in milk whey, but not to homologous bacteria grown in TSB. S. aureus strains grown in milk whey agglutinated in the presence of the polyclonal antibody, whereas the corresponding bacteria grown in TSB did not agglutinate. Immuno-gold particles did not bind to milk whey-grown bacteria treated with periodate. Periodate-treated milk whey-grown bacteria did not agglutinate in the presence of the polyclonal antibody, whereas periodate treatment had no effect on TSB-grown bacteria. PMID- 7869959 TI - Borrelia japonica in nature: genotypic identification of spirochetes isolated from Japanese small mammals. AB - Spirochetes were isolated from earlobe tissues of shrews (Sorex unguiculatus, Sorex caecutiens, and Crocidura dsienezumi), voles (Clethrionomys rufocanus), and mice (Apodemus argenteus and Apodemus speciosus) captured in various localities in Japan. The isolates were identified as Borrelia japonica by rRNA gene restriction fragment length polymorphism analysis. The data suggest that these small mammals are candidates of reservoir hosts for B. japonica. PMID- 7869960 TI - Detection of human cytomegalovirus DNA in breast milk by means of polymerase chain reaction. AB - Three hundred and twenty-five breast milk samples were examined for the occurrence of human cytomegalovirus (HCMV) by cell culture method. Virus was isolated from the milk in 1 of 177 samples collected within 6 days after delivery, 2 of 115 samples collected during the period of 7 days to 1 month after delivery, 10 of 33 samples collected over 1 month after delivery. Next, we tried to amplify HCMV DNA from the breast milk samples from HCMV seropositive mothers and seronegative mothers at 1 month after delivery by polymerase chain reaction. HCMV DNA was detected in 12 of 13 samples from seropositive mothers and in none of 7 samples from seronegative mothers. It was thought that all women seropositive for HCMV principally shed the virus into their breast milk at 1 month after delivery. PMID- 7869961 TI - A novel assay system for anti-human immunodeficiency virus type 1 (HIV-1) activity using a subclone of a monocytic cell line, U937. AB - A subclonal cl.1-14 cell was established from a monocytic cell line U937 by a limiting dilution method. The anti-HIV-1 activity of some antiviral compounds was evaluated in HIV-1-infected cl.1-14 cells. The results demonstrated that although AZT was a potent inhibitor of HIV-1 replication in cl.1-14 cells, its 50% effective concentration (EC50) values was 80 times higher than that in HIV-1 infected MT-4 cells; the EC50 of AZT was 0.16 microM and 0.002 microM in cl.1-14 and MT-4 cells, respectively. In contrast, the anti-HIV-1 activity of ddA, ddI and ddC in cl.1-14 cells was comparable to that in MT-4 cells. The antiviral activity of nevirapine, dextran sulfate, curdlan sulfate and T22 did not differ significantly between the cl.1-14 and MT-4 cells. The antiviral activity of several compounds in the HIV-1-infected cl.1-14 cells was similar to that in the HIV-1JR-FL-infected human peripheral macrophages. Our results suggest that cl.1 14 cell cultures are very useful for estimating antiviral activity and more advantageous than the use of peripheral blood macrophages. PMID- 7869962 TI - Approach to the involvement of influenza B neuraminidase in the cleavage of HA by host cell protease using low pH-induced cell fusion reaction. AB - ts7, a temperature-sensitive mutant defective in neuraminidase (NA) of influenza B/Kanagawa/73, lacks NA enzymatic activity at the nonpermissive temperature (37.5 C). When MDCK cells were infected with the mutant at the permissive temperature (32 C) and exposed to pH 5.2 medium, extensive cell fusion occurred. In contrast, at the nonpermissive temperature cells did not show cell fusion at all unless they were pretreated with trypsin, suggesting that at 37.5 C the hemagglutinin (HA) of ts7 is expressed at the cell surface in an uncleaved form. It was also found that the replacement of RNA segment 6 of ts7 with that of wild-type B/Lee resulted in the emergence of low pH-induced fusion activity as well as NA enzymatic activity at the incubation temperature of 37.5 C and that the addition of bacterial NA to the cultures infected with ts7 at 37.5 C early in infection brought about low pH-induced cell fusion. We suggest that the removal of neuraminic acid from the carbohydrate moiety of HA by NA is essential for the cleavage of HA by cellular protease. PMID- 7869963 TI - Interspecies transmission of animal rotaviruses to humans as evidenced by phylogenetic analysis of the hypervariable region of the VP4 protein. AB - A phylogenetic tree constructed for the hypervariable region (aa 71-203) of the VP4 protein of 28 human and animal rotaviruses that were previously reported to belong to 13 distinct VP4 genotypes revealed unique positions of human rotavirus strains HCR3 and Ro1845, together with feline strain FRV64 and canine strains K9 and CU-1, in the animal rotavirus lineages, lending strong support to the view that both HCR3 and Ro1845 were of animal rotavirus origin. PMID- 7869964 TI - Detection of west Nile and Japanese encephalitis viral genome sequences in cerebrospinal fluid from acute encephalitis cases in Karachi, Pakistan. AB - Reverse transcriptase-polymerase chain reaction (RT-PCR) on 24 cerebrospinal fluid (CSF) specimens collected between February and August 1992 detected genome sequence of West Nile (WN) virus in 8 specimens and Japanese encephalitis (JE) virus in a single specimen. The results, combined with the data by IgM-ELISA on CSF indicated that a significant proportion of acute encephalitis cases in Karachi, Pakistan, were caused by WN virus infection, while JE virus caused a small fraction. PMID- 7869965 TI - [Progress in molecular biology]. PMID- 7869966 TI - [Diseases of the facial nerve]. PMID- 7869967 TI - [Contact lenses]. PMID- 7869968 TI - [Immunologic characterization of autoreactivity to nuclear antigens in patients with systemic lupus erythematosus]. AB - Abnormal immune reactivity, with a production of multiple autoantibodies specially against the components of a nucleoplasm is one of the hallmarks of systemic lupus erythematosus (SLE). Our investigations were conducted on 102 patients with SLE, classified according to the criteria of ARA, aiming to better characterize the overall incidence of anti-nuclear antibodies in SLE, to determine the type of immunofluorescent staining of the nuclei, and to characterize the fine specificity of such antibodies using modified ELISA procedure. Results of our investigation show that 95% of patients with SLE have detectable anti-nuclear antibodies. Predominant pattern of nuclear staining is homogeneous, followed by a speckled type, while the rim (peripheral) pattern is relatively infrequent. Anti-nuclear antibodies showed the highest reactivity against native DNA (70% of patients), which was followed by binding to SS-A, eRNP and SS-B antigens. Interestingly, using ELISA procedure we could observe the reactivity against Sm antigen only in 5% of SLE patients. In patients who showed homogeneous or rim pattern of nuclear staining the predominant type of reactivity was against native DNA, while in patients with speckled type most frequent binding to non-histone proteins was observed. The most frequently observed individual pattern of ANA reactivity was of polyreactive type. PMID- 7869969 TI - [Free urinary cortisol in the diagnosis of hypercorticism]. AB - 24 hour urinary free cortisol has lower values in suspect obese patients compared to patients with Cushing's syndrome. The most favourable discriminatory border value of urinary cortisol is 100 micrograms/24 hours, giving the most valid differentiation of obese patients suspected for Cushing's syndrome from patients with hypercortisismus. Free cortisol has far expressive discriminatory value compared to 17-OHCS, and it is a good screening test in differential diagnosis of obese suspected patients from patients with Cushing's syndrome. PMID- 7869970 TI - [Ultrastructure of pigmented skin nevi]. AB - Nevus cells are biologically significant because they are associated with epidermal melanocytes, while their clinical malignant melanomas. Apart from many other ultrastructural features their mutual characteristic is that they are exceptionally diverged. The main feature distinguishing nevus cells from melanocytes is the presence of big binuclear cells as well as frequent occurrence of grouped melanosomes in their cytoplasm. PMID- 7869971 TI - [Histoenzymologic features of adrenal medulla ganglionic cells 60 days after exposure to detergents]. AB - We investigated histochemical reactions in adrenal medulla sympathic ganglionic cells in the animals who after a 30-day stay in a detergent manufactory department survived 60 days in laboratory conditions. The obtained data show a strong isocytrate dehydrogenase activity in the experimental animals; the reaction to the lactate dehydrogenase activity reflects a decrease of the ganglionic cell volume and a slight decrease of the reaction intensity. The activity of isoenzyme F is mildly increased; similarly was found for isoenzyme S. There was a significant decrease of the succinate dehydrogenase activity--all this was detected in the animals exposed to detergents. Sympathic ganglionic cells within the adrenal medulla are rather sensitive to the influence of detergents. The recovery after the exposure to their toxic effects takes more than 2 months. PMID- 7869972 TI - [Large dermoid cysts of the mouth floor]. AB - Dermoid cysts of the mouth floor are very rare. The incidence of these cysts is up to 3.6% of all cysts in the oral cavity. The article presents the material from the Clinic of Maxillofacial Surgery MMA. Eleven cases of large dermoid cyst are discussed. All of them were removed completely and no recurrence developed in longer period of time postoperatively. PMID- 7869973 TI - [Meningococcal sepsis and difficulties in differential diagnosis--case report]. AB - We report a case of meningococcal sepsis in a healthy immunocompetent sixteen year old boy who had developed upper respiratory tract acute infection 10 days before the admittance. Clinical manifestations were similar to those found in allergic hemorrhagic purpura (Schonlein's form of the disease). The clinical course of these two diseases is usually different but sometimes they cannot be easily differentiated. The acute onset of polyarthritis, temperature and skin manifestations in the form of erythematous maculopapular exanthema which within several hours evolved into hemorrhagic purpura is typical for the sepsis caused by Neisseria meningitides but these characteristics might be found in allergic Henoch-Schonlein' purpura as well. In our case the accurate diagnosis was set by the identification of the group C Neisseriae meningitides from the patient's blood. The first choice was penicillin therapy. PMID- 7869974 TI - [Nerve lesions after acute anterior dislocation of the humero-scapular joint- electrodiagnostic study]. AB - We present a pilot seria of 18 patients with acute anterior dislocation of the shoulder joint following simple trauma. All the patients underwent conservative treatment using a standard Kocher technique. In the majority of cases muscular spasm and pain rendered through neurological examination difficult to perform. All patients were, therefore, submitted to extensive electrodiagnostic procedure which revealed a nerve injury on half of them. Such high incidence was, probably, due to the increased age (17 out 18 patients were over 40 years old), and rather traumatic reduction procedure. The axillary nerve was the most frequently affected (38.8%), either alone or in combination with musculocutaneus nerve. Comparing to previous reports in the literature, we found musculocutaneus nerve lesion in a rather high number of patients (22%). Extensive electrodiagnostic study is therefore recommended when further treatment and prognosis of anterior dislocation of the shoulder are taken in consideration. PMID- 7869975 TI - [Personal experience in the treatment of chronic secretory otitis in children]. AB - The authors review their experiences in the treatment of secretory otitis in children. They detected a significantly higher number of positive allergometric tests to standard groups of inhalation allergens than expected. The patients were divided into two groups; in the first group the allergometric test was negative, in the second positive. The therapeutical approach was identical, consisting of the initial medicamentous treatment which did not give any results. After this, adenoidectomy, paracentesis with secretion aspiration and aeration tube implantation were performed in general endotracheal anesthesia. The comparison of the results of the treatment showed that allergic disease, being one of the etiological factors, significantly influence the course of the treatment as well as the prognosis of the disease. It has been concluded that allergy, an etiological cause of chronic secretory otitis in children, should be given a special regard to help an adequate approach to the phenomenon. PMID- 7869976 TI - [Modern approach to the therapy of viral croup]. AB - Viral croup as the most frequent of laryngeal obstructions in childhood appears in the form of spasmodic croup and acute laryngotracheitis. The evaluation of the severity of laryngeal obstruction can be made by using score systems. In more severe forms of viral croup the inhalation of 0.25 ml/kg 2.25% epinehrine and a single dose dexamethasone 0.6 mg/kg i.m. is recommended. PMID- 7869977 TI - [Postspinal headache--incidence and prognosis]. AB - Spinal anaesthesia was performed in 776 adult patients with 22 G and 25 G spinal needle. The incidence of postdural puncture headache was 3.5%. Its association to age, sex, needle size, duration of postoperative recumbency was analyzed. Our results show that the age was a significant predictor of postlumbar puncture headache. Postspinal headache was more often found in younger patients (p < 0.001). PMID- 7869978 TI - [Sexual information and practice in 16-year-old adolescents]. AB - We conducted an anonymous poll among 221 girls and 106 boys from the second grade of secondary schools in Somboru, Crvenka and Ruski Krsturu in order to collect data on some aspects of their sexual knowledge and behavior. By the 16th year of life 8.6% of the girls and 36.8% of the boys experienced coitus, while 48% of the girls and 72% of the boys experienced intimate caressing with the opposite sex. It has been assessed that their knowledge on the physiology of the sexual life and contraception is poor and overestimeted, especially among the boys. The sources of information are mostly inadequate which necessitates an organized approach to sexual education. PMID- 7869979 TI - [Chlamydia trachomatis as a cause of infection in women]. AB - A sample of 596 women was examined by the direct immunofluorescent test (DIF) for the detection of chlamydia brachomatis antigens in the endocervical smear (with monoclonal antibodies), ELISA test for the detection of IgG antibodies against the group chlamydia-antigen. The chlamydia trachomatis infection was found in 30.20% of the cases, with a high positive rate in all age groups. These infections were more frequently found in women in whom sterility had been diagnosed, compared to other examined women. In relation to other inflammatory processes the significantly highest rate was found in women with changes in the cervix (endocervicitis and arythroplakia). A high rate of chlamydia positive (42.44%) was detected in women who had had pathological pregnancies and deliveries. Humoral immune response to the presence of chlamydia trachomatis infection was proved in 79.44% of the cases. We showed and analyzed diagnostic possibilities of the used diagnostic tests where a combination of the DIF test and ELISA was found the best. For a successful diagnosis two methods have been recommended: a direct one-for the detection of the cause (DIF test, isolation in the cell culture McCoy or Hela 229) and an indirect one for the detection of specific antibodies in the serum. PMID- 7869980 TI - [The postoperative status of the gastroduodenum--clinical and endoscopic analysis of 2 years' of hospital data]. AB - In 72 patients operated on for gastric ulcer, hospitalized at the Clinic of Gastroenterology and Hepatology in Novi Sad within two years (1989, 1990) we analyzed clinical disorders, biochemical status and endoscopic findings. 75% of the patients were males and 25% females, mean age being 49 years. In 70.83% the two-thirds Billroth II resection was performed, in 15.28% the two thirds Billroth I resection, in 9.72% truncal vagotomy with pyloroplasty, while in 4.17% supraselective vagotomy was carried out. The mean period of time after the operation was 12 years. The majority of patients complained about gastrointestinal disorders, and manifest hemorrhage was detected in 4.17% of the patients. The symptoms of the afferent loop syndrome and early dumping syndrome were verified in one patient from each group. The endoscopic finding was normal in only 2.78%, reflux esophagitis in 6.94%, chronic gastritis with and without erosions in 86.11%, chronic anastomositis in 69.44%, recurrent ulcer in 29.16% out of which hemorrhagic ulcer was found in 4.17%. Malignant neoplasm of the stomach stump was endoscopically evidenced and histologically proved in 2.78%. Multiple associated endoscopic changes were found in 58.33%. The analysis indicates the diversity of postoperative disorders after one of the operations on gastroduodenum, requiring postoperative follow ups of the patients with subjective discomfort, appropriately set diagnosis and individual therapeutical approach to prevent more serious complications. PMID- 7869981 TI - [Promotion of a positive image of health behavior by the population via primary health care system activities]. AB - The aim of this investigation was to find out the possibilities and the necessity of health educational and health promotion programmes in the working population. The study was performed during 1991 in Vojvodina. The representative sample was selected among the industrial, administrative and agricultural workers. The results showed high participation of inadequate health behaviour among the questioned workers. But there is a strong wish for its correction among them, and expressed need for help in doing it. There was a high interest in health topics, but the main sources for these informations were mass media and selfexperience, and finally health workers. This shows the need for more active participation of health personnel in health education and health promotion. The paper suggests the promotion of health behaviour among the working population as a mutual activity of primary health workers and the working organization. PMID- 7869982 TI - [Phenotyping: personal contribution to research on increased susceptibility of individual HLA phenotype combinations in predisposition to contact allergies]. AB - We determined the A and B locus antigenic phenotype structure by means of the lymphocytotoxic test (Terasaki) in 43 subjects with allergic contact dermatitis verified by the Patch test, as well as in 103 healthy subjects (control group). Statistical fashioning was carried out by counting all of the phenotypes in the group examined by using the 2 x 2 table the X2 test with -correction according to Yates. In a case of an existing difference in frequency, the relative risk (RR) (Svejgaard) was determined. When RR was greater relation with the disease exists with the antigen which was found to have a greater EF value (Bengtsson). A statistically significant increase of A1 antigen frequency and decrease of A28 antigen frequency, as well as the absence of B13 and BW41 antigens in the group examined can be considered as a contribution in clarifying the genetic component in contact allergy etiopathogenesis. PMID- 7869983 TI - Rotary scanning equalization radiography: an efficient geometry for equalization mammography. AB - The detection of cancer in the radiographically dense breast is problematic, since the breast will produce a range of exposure that exceeds the useful dynamic range of high contrast film-screen combinations. It has been shown previously that mammographic scanning equalization radiography (MSER) can be used to overcome the latitude limitations of film-screen mammography. However, the tube loading of MSER is orders of magnitude greater than conventional mammography. A new rotary geometry for equalization radiography is proposed, in which the image receptor is exposed by repeated scans of a modulated slot beam, oriented at a variety of scanning angles with respect to the object. The superposition of the exposure from appropriately modulated, rotated slot beams produces an entrance exposure that will effectively equalize the film exposure. The principle advantages of this geometry is its simplicity and reduced tube loading. To determine the effectiveness and feasibility of RSER the effect of conventional, MSER, and RSER have been numerically simulated on the appearance of clinical mammograms, the relative heat loading, and the fraction of the breast imaged with high contrast are calculated. It is found that RSER produces images that are free of artefacts, and exhibit a similar degree of equalization, as found in MSER images. RSER accomplishes this with only four scanning angles, and a beam that is approximately 4 cm wide. The resulting tube loading is only three times greater than that found in conventional imaging. Numerical simulations indicate that RSER is a simple, feasible means of overcoming the latitude limitations of film-screen mammography. PMID- 7869984 TI - On the fractal nature of trabecular structure. AB - Fractal analysis has recently been suggested [Med. Phys. 20, 1611-1619 (1993)] as a means to characterize the structure of cancellous bone by measuring the fractal dimension using a box counting algorithm. This work re-examines the possible fractal nature of such structures on nuclear magnetic resonance (NMR) images of cancellous bone by estimating the trabecular boundary length as a function of box size under various experimental conditions. On high-resolution images (pixel sizes on the order of 50 microns) and signal-to-noise ratios of 30, the trabecular boundary turns out to be a smooth surface relative to the achievable resolution and is thus nonfractal. The fractal dimension of the trabecular structure is undefined and can vary significantly as a function of image signal to-noise ratio. The present work further indicates the "apparent" fractal dimension obtained by box counting to be a reflection of marrow pore size. In conclusion, the results indicate that, at the currently achievable resolution, the box counting algorithm is not suitable for fractal analysis on images of cancellous bone and that the fractal appearance of the trabecular network reported previously is artifactual. PMID- 7869985 TI - An analytical edge spread function model for computer fitting and subsequent calculation of the LSF and MTF. AB - The previous work of Yin, Giger, and Doi [Med. Phys. 17, 962-966 (1990)] demonstrated that using a computerized fit of an analytic line spread function to experimentally measured data is very useful for determining the presampling modulation transfer function of an imaging system. In this report, the work of Yin et al. is extended to include an analytic expression for the edge spread function (ESF). By fitting experimentally determined edge spread function data to the analytical expression, the normalized line spread function (LSF) and the normalized modulation transfer function (MTF) can be easily calculated from four ESF fit coefficients. The extension from the line spread function to the edge spread function should be valuable in cases where slit measurements are impractical, for example, in very high resolution imaging systems where the required slit dimensions become impractically small, or in measurements of the transfer properties of scattered radiation or off-focus radiation, where large area exposures are necessary. PMID- 7869986 TI - Flattening of the contrast-detail curve for large lesions on liver CT images. AB - This study evaluated the relative roles of physical and perceptual factors in flattening the contrast-detail (CD) curve on liver CT scans. To estimate the role of physical factors, the theoretical CD curve for a calculated theoretical observer (i.e., a nonprewhitening matched filter) was predicted using the measured noise power spectrum and measured modulation transfer function of the CT system. Another theoretical CD curve was also produced from the output of the same calculated observer after taking the human visual response function (VRF) into account. Perceptual factors were evaluated by analyzing human observers' replicated ratings of the visibility of details super-imposed on liver CT scans. The CD curve for the calculated theoretical observer was below the CD curve actually measured for nine human observers and showed no flattening. With the VRF included, flattening of the theoretical CD curves was only produced by fixed image viewing distances of less than 30 cm, a reading style not employed by the human observers. Correlated ROC analysis of observers' replicated ratings indicated that while random, intraobserver variation was present, the magnitude of this so-called observer noise was insufficient to explain the flattening of CD curves. Use of narrow display windows did not eliminate this flattening effect. The main reason for human observers' inefficient detection of large, low contrast liver lesions appears to be a consistent misuse of the image information. PMID- 7869987 TI - A variable-resolution rotate-only computed tomography scanner. AB - The Rotoscan is a computed tomography scanner that combines the advantages of variable geometric resolution and adjustable size of measurement diameter of translate-rotate scanners with the improved speed of rotate-only scanners. Because of the small number of only 26 detectors used for this scanner, a special data collection scheme of multiple rotations with interleaved detector positions was employed. In order to avoid angular data interpolation after reordering of the projections from the fan- to a parallel-beam geometry, the detectors were incrementally moved at a right angle to the centerline of the fan rather than rotated about the source. The measurement time of 40 s for one cross-section is comparable to that of second-generation systems. However, for longer measurement diameters, the measurement time for second-generation systems increases, whereas that of the Rotoscan remains constant. PMID- 7869988 TI - A simulation of emission and transmission noise propagation in cardiac SPECT imaging with nonuniform attenuation correction. AB - Transmission computed tomography provides information needed for nonuniform attenuation correction of cardiac single photon emission computed tomography (SPECT). Nonuniform attenuation correction is accomplished using an iterative ML EM algorithm and a projection-backprojection operation that incorporates attenuation factors measured from the reconstructed transmission map. The precision and accuracy of the attenuation corrected emission reconstruction is a function of emission and transmission statistics. This paper presents an error propagation analysis that uses a mathematical cardiac chest phantom to simulate various combinations of total emission counts C and transmission flux I0 under ideal imaging conditions (without geometric response distortion and without scatter). The spatial average, spatial variance, and accuracy measures for a 4 x 4 pixel region in the heart are tabulated after 30 iterations of the ML-EM algorithm. The confidence intervals for these measures were determined from 1000 realizations of reconstructions from projections randomly generated with the same transmission and emission statistics. It can be shown empirically from the simulation results that the spatial %rms uncertainty for the simulated cardiac region has a simple expression: %rms2 = K1/C+K2/I0(2)+B2 where K1 and K2 are least-square estimates based on the simulation results, and B is the measured spatial %rms uncertainty for the simulation at infinite statistics. For a transmission incident flux of 1500 events per projection bin of 0.712 cm and typical clinical emission events totaling 1 x 10(5), the spatial %rms uncertainty is approximately 14%. At clinical transmission and emission statistics, the statistical noise in the simulated attenuation-corrected reconstructions are dominated by the emission statistics. PMID- 7869989 TI - A new dual-isotope convolution cross-talk correction method: a Tl-201/Tc-99m SPECT cardiac phantom study. AB - Simultaneous dual-isotope SPECT imaging provides a clear advantage in situations where two concurrent metabolic, anatomic, or background measurements are desired. It obviates the need for two separate imaging sessions, reduces patient motion problems, and provides exact image registration between images. However, a potential limitation of dual-isotope SPECT imaging is contribution of scattered and primary photons from one radionuclide into the second radionuclide's photopeak energy window, referred to here as cross-talk. Cross-talk in both photopeak energy windows can significantly degrade image quality, resolution, and quantitation to an unacceptable level. Simple cross-talk correction method used in dual-radionuclide in vitro counting, even applied on a pixel-by-pixel basis, does not account for the differences in spatial distribution of the photopeak and cross-talk photons. Here a new convolution cross-talk correction method is presented. The convolution filters are derived from point response functions (PRFs) for Tc-99m and Tl-201 point sources. Three separate acquisitions were performed, each with two 20% wide energy windows, one centered at 140 keV and another at 70 keV. The first acquisition was done with Tc-99m solution only, the second with Tl-201 solution only, and the third with a mixture of Tc-99m and Tl 201. The nonuniform RH-2 thorax-heart phantom was used to test a new correction technique. The main difficulty and limitation of the convolution correction approach is caused by the variation in PRF as a function of depth. Thus, average PRF should be used in the creation of an approximative filter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869990 TI - The accuracy of SPECT brain activation images: propagation of registration errors. AB - Functional single photon emission computed tomography (SPECT) images of brain activation are based on a comparison of base line and activation images. The correctness of the functional images depends, among other factors, on the accurate spatial registration (alignment) of the base line and activation image data. The relationship between the registration errors and the errors of the resulting functional images is studied. It is shown that misregistration errors as small as a shift by 1/8 pixel or rotation by 1 degree result in 5%-10% errors of the pixel values of functional SPECT images of regional blood flow (the ratio and the relative difference images). PMID- 7869991 TI - Inclusion of energy straggling in a numerical method for electron dose calculation. AB - Energy straggling along electron trajectories has been incorporated into a numerical algorithm for electron beam dose calculations. Landau's theory is used to predict, at any point in the absorber, the broadening of the primary electron energy spectrum due to energy loss straggling. Numerical calculations have been performed for electron beams with energies of 10-30 MeV incident upon water in order to determine the variation of dose with depth and variation of energy spectra with pathlength. These calculations are compared with the results of Monte Carlo simulations performed with the EGS4 code. The inclusion of energy loss straggling in the numerical calculations leads to predictions of energy spectra and dose deposition that are in good agreement with modified Monte Carlo simulations in which bremsstrahlung is ignored and the energy given to knock-on electrons is deposited at the site of their creation. Less satisfactory agreement was achieved when these calculations were compared to full Monte Carlo simulations that included the bremsstrahlung events and transported the knock-on electrons. It is concluded that bremsstrahlung energy loss must also be included into this algorithm, if an acceptable dose computation accuracy is to be achieved for clinical applications. PMID- 7869992 TI - Dosimetry for asymmetric x-ray fields. AB - Conventional linear accelerators have four field-defining jaws or collimators. Usually, one set of the two opposing jaws moves concurrently to define the field width and the other set defines the field length. The resultant square or rectangular field will have the field centerline coincide with the collimator axis. However, some modern linacs have independent collimators or jaws that can be set asymmetrically. In this case, one of the two opposing jaws can be closed down independently of the other one to define an asymmetric field of smaller dimension. The field center now does not coincide with the collimator axis. Asymmetric collimators have found many clinical applications, but have complicated the dosimetry for physicists. Data acquisition and treatment planning implementations are tedious and complicated. An algorithm has been developed to correct for the reduced dose in the smaller asymmetric field. The approach used is similar in principle to the Day's equivalent field calculation. The difference in dose between an asymmetric and a symmetric radiation field is accounted for by a correction factor that is a function of the asymmetric and symmetric field sizes, off axis distance, and depth of measurement. The correction method presented here applies only to the closing down of one independent jaw. Beam profiles for asymmetric fields are measured for both the 6 and 10 MV photon beams.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869993 TI - A precise investigation on the TL behavior of LiF: Mg, Cu, P (GR-200A). AB - LiF: Mg, Cu, P is a TL material presenting unique dosimetric features. The TL sensitivity of this material was studied as a function of the annealing temperature and of the repeated cycles of annealing-irradiation-readout. A fading study was carried out over a period of 40 days with the purpose of checking the stability of the stored dosimetric information as a function of different annealing temperatures. A detailed statistical analysis of sets of data, obtained from repeated measurements on a group of ten dosimeters, is presented. PMID- 7869994 TI - Mixed field dosimetry of epithermal neutron beams for boron neutron capture therapy at the MITR-II research reactor. AB - During the past several years, there has been growing interest in Boron Neutron Capture Therapy (BNCT) using epithermal neutron beams. The dosimetry of these beams is challenging. The incident beam is comprised mostly of epithermal neutrons, but there is some contamination from photons and fast neutrons. Within the patient, the neutron spectrum changes rapidly as the incident epithermal neutrons scatter and thermalize, and a photon field is generated from neutron capture in hydrogen. In this paper, a method to determine the doses from thermal and fast neutrons, photons, and the B-10(n, alpha)Li-7 reaction is presented. The photon and fast neutron doses are measured with ionization chambers, in realistic phantoms, using the dual chamber technique. The thermal neutron flux is measured with gold foils using the cadmium difference technique, the thermal neutron and B 10 doses are determined by the kerma factor method. Representative results are presented for a unilateral irradiation of the head. Sources of error in the method as applied to BNCT dosimetry, and the uncertainties in the calculated doses are discussed. PMID- 7869995 TI - Design of a high-flux epithermal neutron beam using 235U fission plates at the Brookhaven Medical Research Reactor. AB - Beams of epithermal neutrons are being used in the development of boron neutron capture therapy for cancer. This report describes a design study in which 235U fission plates and moderators are used to produce an epithermal neutron beam with higher intensity and better quality than the beam currently in use at the Brookhaven Medical Research Reactor (BMRR). Monte Carlo calculations are used to predict the neutron and gamma fluxes and absorbed doses produced by the proposed design. Neutron flux measurements at the present epithermal treatment facility (ETF) were made to verify and compare with the computed results where feasible. The calculations indicate that an epithermal neutron beam produced by a fission plate converter could have an epithermal neutron intensity of 1.2 x 10(10) n/cm2.s and a fast neutron dose per epithermal neutron of 2.8 x 10(-11) cGy.cm2/nepi plus being forward directed. This beam would be built into the beam shutter of the ETF at the BMRR. The feasibility of remodeling the facility is discussed. PMID- 7869996 TI - Thick beryllium target as an epithermal neutron source for neutron capture therapy. AB - Accelerator-based intense epithermal neutron sources for Neutron Capture Therapy (NCT) have been considered as an alternative to nuclear reactors. Lithium (Li) has generally received the widest attention for this application, since the threshold energy is low and neutron yield is high. Because of the poor thermal and chemical properties of Li and the need for heat removal in the target, the design of Li targets has been quite difficult. Beryllium (Be) has been thought of as an alternative target because of its good thermal and chemical properties and reasonable neutron yield. However, in order to have a neutron yield comparable to that of a thick Li target bombarded with 2.5 MeV protons, the proton energy required for a thick Be target must be approaching 4 MeV. Consequently, the neutrons emitted are more energetic. In addition, a significant amount of high energy gamma rays, which is undesirable, will occur when Be is bombarded with low energy protons. Regardless of the more energetic neutrons and additional gamma rays, in this paper it is shown that it is possible to develop a high-quality and high-intensity epithermal neutron beam based on a thick Be target for NCT treatment. For a fixed proton current, the optimal Be-target-based beam (with 4 MeV protons) can produce a neutron beam, with both quality and intensity slightly better than those produced by the optimal Li-target-based beam (with 2.5-MeV protons). The single-session NCT treatment time for the optimal Be-target-based beam is estimated to be 88 min for a proton current of 50 mA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7869997 TI - [The effect of obesity on outcome of kidney transplantation]. AB - BACKGROUND AND AIM: Obesity is a risk factor for postoperative complications in surgery. In a retrospective study we investigated the course of body weight during the waiting period and the first postoperative year and the influence of obesity on graft function. PATIENTS AND METHOD: The medical records of 334 adult patients undergoing cadaveric kidney transplantation between 1986 and 1992 were reviewed. Immunosuppression was performed with cyclosporine and prednisone. For all patients the Broca index was calculated with the relative body weight by the formula: body weight/Broca index x 100 (% BI). Obesity was defined as relative body weight > or = 120% BI. RESULTS: At the time of the indication for kidney transplantation 15.3% of the patients were obese. Only 12 of these 51 obese patients reduced their body weight below 120% BI until transplantation, whereas 25 patients increased weight in excess of 120% BI. Thus the number of obese patients raised to 19.2% by the time of transplantation. The graft survival in the obese group was significantly lower than in the nonobese group. This difference appeared already in the first half year after transplantation being constant in the following time. The resulting 1-year graft survival was 82.8% and 91.4% respectively (p < 0.05). During the first year 59 patients more became obese, the percentage of obese raised up to 36.0%. One year after transplantation there was no longer significant difference of graft survival rate in the further follow-up between obese and nonobese patients. CONCLUSION: Our findings show, that obesity is an important risk factor for early graft loss. Therefore all participating physicians assume a great responsibility for the pre-operative treatment during the waiting time. PMID- 7869998 TI - [The Gitelman syndrome--a differential diagnosis of Bartter syndrome]. AB - BACKGROUND: Hypokalemia due to renal potassium wasting in the absence of hypertension, moderate metabolic alkalosis, hyperreninism and hyperaldosteronism suggest the presence of Bartter's syndrome. The underlying cause is an inherited defect of sodium chloride reabsorption in the thick ascending limb of Henle. A differential diagnosis of Bartter's syndrome is Gitelman's syndrome, another hypokalemia-hypomagnesemia syndrome, which is thought to be caused by a transport defect in the distal tube. PATIENTS AND METHODS: We report 3 patients presenting with signs primarily suggestive of Bartter's syndrome, who turned out to have Gitelman's syndrome after determining the excretion of calcium in the urine. RESULTS: Two women, 36- and 55-year old, suffered from paresthesias in the hands and feet and from tetanic convulsions. The brother of the 36-year old woman presented in our hospital because of an accidentally discovered hypokalemia without any clinical symptoms. In all patients the outstanding biochemical features were hypokalemia, hypomagnesemia and moderate metabolic alcalosis. The renin and aldosterone values were inappropriately high. The most characteristic finding in the urine, besides the presence of hyperkaliuria was the diminution of calcium excretion, despite normocalcemia. CONCLUSION: The association between sodium and calcium reabsorption in the loop of Henle predicts hypercalciuria in patients with a defect in salt reabsorption in this segment, as in Bartter's syndrome. In Gitelman's syndrome the laboratory features resemble the findings in Bartter's syndrome, except for the presence of hypocalciuria. Since hypocalciuria follows also the administration of thiazide diuretics, which act in the early part of distal tube, a transport defect in this part of the tube is thought to be responsible for the electrolyte disturbances in Gitelman's syndrome. The measurement of the urinary calcium excretion in patients with an unclear hypokalemia-hypomagnesemia-syndrome allows easily the differentiation between Bartter's and Gitelman's syndrome. PMID- 7870000 TI - [Clinical infectiology update. I: Diagnosis, pathogen spectrum and resistance]. PMID- 7869999 TI - [Effectiveness of plantago seed husks in comparison with wheat brain on stool frequency and manifestations of irritable colon syndrome with constipation]. AB - BACKGROUND AND AIM: The importance of dietary fibres in treatment of irritable bowel syndrome increased during the last years. Yet the results of clinical studies on the different dietary fibres are not consistent. Therefore we decided to perform a controlled trial with a well defined group of patients to compare the effectiveness of wheat bran to psyllium seeds. PATIENTS AND METHODS: Thirty patients each with irritable bowel syndrome group II to III were treated in an open, not controlled study design either with 3 times 3.25 g psyllium seeds or 3 times 7 g wheat bran daily. All patients entering the study had not been treated for at least 3 weeks before. The study comprised two treatment phases of two weeks each, separated by two weeks without any treatment, thus leading to a study duration of 6 weeks altogether. Parameters for evaluation were stool frequency and consistency and the symptoms pain and abdominal distention, measured by a score (1 to 4). RESULTS: In both treatments groups stool frequency and consistency improved apparently compared to the starting point or the two weeks treatment free time in between. The improvement of stool frequency was statistically significant (p < 0.0001) for both substances. Furthermore the effect of psyllium seeds exceeded that of wheat bran statistically significant in week 1, 2, 3, 5 and 6 (p < 0.005). Other symptoms such as abdominal pain improved too by therapy, psyllium seeds again tending to show better results. A significant difference between both substances could be observed on the symptom abdominal distension. Whereas abdominal distension decreased under treatment with psyllium seeds it increased with wheat brain. This lead to discontinuation of the study in 5 cases, 3 of which could be changed successfully to psyllium seeds. The difference between psyllium seeds and wheat bran concerning the occurrence of abdominal distension was statistically significant (p < 0.01). CONCLUSION: The results of this study demonstrate the effectiveness of psyllium seeds and wheat bran on stool frequency and consistency of patients with irritable bowel syndrome. Psyllium seeds showed to be superior to wheat brain with respect to stool frequency and abdominal distension so that it should be preferred in treatment of irritable bowel syndrome and constipation. PMID- 7870001 TI - [Action of intrinsic low density lipoprotein in the vascular wall. Significance for the pathogenesis of essential hypertension and arteriosclerosis]. PMID- 7870002 TI - [Theophylline: new information about a proven drug. The dual effect in therapy of bronchial asthma]. PMID- 7870003 TI - [Theophylline--at 100 years old into its 4th life]. PMID- 7870004 TI - [Experiences with taxanes exemplified by paclitaxel (taxol) for internal medicine oncologic indications]. PMID- 7870005 TI - [Cardiac toxicity of 5-fluorouracil]. PMID- 7870006 TI - [In right-left shunt measure kidney perfusion]. PMID- 7870007 TI - [The pediatrician and the hepatitis B vaccine]. PMID- 7870008 TI - [Evaluation of the immune status of children never treated wtih chemoantibiotics (children 3 to 6 years old)]. AB - Six children aged between three and six years, born from undamaged families and free from malformative, chronic, degenerative or metabolic diseases, never treated with chemoantibiotics, were checked for their immune status. They were compared with other six children with the same somatic characteristics, the same health status and the same economical-social condition as the first six ones; but frequently treated with chemoantibiotics (not less than three therapy periods during each year of their life). The comparative study was performed by checking various parameters (lymphocyte blastization; rosette "E"; T3, T4, T8 lymphocytes with T4/T8 ratio; B lymphocytes; NK cells, chemotaxis; phagocytosis; killing; serum immunoglobulins A, G, M; C3; C4) index of immune functions, in uniform conditions. Results were statistically elaborated by means of "t-Student between groups test", "on ordinal ranks test", "t-Student for paired data test" and "Pearson's correlation coefficient" calculation. Significative differences by means of "t-Student between groups test" were recorded for what C3 is concerned, higher in never treated children, for PWM stimulation Blastization, lower in never treated children, for unstimulated blastization, chemotaxis and plasma IgM lower in frequently treated children. By means of "t-Student for paired data test" the above mentioned differences were confirmed and significantly higher values of plasma Immunoglobulin G and B lymphocyte in never treated children were pointed out. The differences between the last children and the controls are much higher than those previously recorded between similar groups 6-12 years old. PMID- 7870009 TI - [2 cases of Beckwith-Wiedemann syndrome. Morphogenetic characteristics, cardiac involvement and current diagnostic possibilities]. AB - This report describes two new cases of BWS. This diagnosis of BWS may be missed because of variable or incomplete clinical expression. Recognition of such patients is important, however, because they have the potential for development of neoplasias. There also appears to be an increased risk of malignancies associated with hemihypertrophy and BWS. PMID- 7870010 TI - [Determination of the cut-off for marker TPA in healthy children]. AB - In the present study the authors investigated the normal range of the marker TPA in the sera of 100 children (apparently healthy) aged from 0 to 6 years. Well defined criteria as guide-lines to the interpretation of laboratory results are a very urgent necessity for the expanding utilization of clinical laboratory data. To avoid possible mistakes on such an important area as new MT for the definition of a decisional standard for all the most relevant laboratory marker test. All patients have serum TPA values of less than 95 U/l and confirmed the distribution of TPA values in healthy individuals. PMID- 7870011 TI - [HuEPO treatment of anemia in preterm infants]. AB - The aim of this study is to evaluate how many blood transfusions can be saved by the treatment of anemia in preterm infants (eg < or = 33 weeks) with HUEPO. VLBW infants are at high risk of receiving blood transfusions, following the blood transfusion criteria most applied (45-50% of VLBW infants need blood transfusions). A review of the most recent studies shows that we can save a remarkable number and quantity of blood transfusions in the VLBW infants treated with HUEPO. PMID- 7870012 TI - [Brucellosis in childhood: therapeutic contribution]. AB - We report a case of Brucellosis in a seven year old child satisfactorily cleared up after therapy with ceftriaxone. We analyze the advantages of the drug in pediatric practice compared with usual therapy. The review of some clinical trials about use of the drug in treatment of Brucellosis is not conclusive. The use of the drug with higher dosages than the ones used by mentioned Authors is suggested. PMID- 7870013 TI - Assessing children for the effects of sexual victimization. AB - In summary, the psychological assessment of sexually abused children is complicated significantly by the fact that there is no single syndrome that reflects the impact of sexual abuse (Kendall-Tackett, Williams, and Finkelhor, 1993). A number of generic measures of psychopathology in children continue to find large percentages of children relatively asymptomatic. This is due to the variability in impact of sexual abuse, but also reflects the need to develop abuse-specific outcome measures. Because we are discussing the evaluation of children, psychological assessment must be developmentally sensitive and reflect the context of the child (Stewart, Bussey, Goodman, and Saywitz, 1993). Consequently, information should be obtained not only from parents and children, but from the entire family. Unless an evaluation includes some abuse-specific measures and examines findings about the child in the context of the larger family environment, it is not likely to be valid. The interrelationship of abuse impact on parental perception and subsequent parental accuracy in reporting also must be examined in more detail. Not surprisingly, maternal reports of their sexually abused child's emotional states are strongly correlated with their own distress (Newberger, Geremy, Waternaux, and Newberger, 1993). This confound necessitates input from teachers or other objective observers of the child. The evaluation of sexually abused children should be theoretically driven. I strongly recommend assessing both the child and the parents with regard to attachment quality, difficulties with self-regulation, and an impaired sense of self. There are a number of measures pertinent to both parents and children across each of these domains. However, measures must be developed and validated that allow for parent, child, and teacher report in the areas of sexual behavior, sexual concerns, sexual meaning, body integrity, abuse-specific aspects of self (such as blame, shame, and dissociation), PTSD, abuse-specific fears, and family-related variables of rejection and role reversal. There is a developing literature that supports the need to assess each of these domains in a multimodal manner. PMID- 7870014 TI - Long-term correlates of childhood sexual abuse in adult survivors. AB - Empirical research demonstrates a relationship between history of child sexual abuse and numerous psychological, interpersonal, and behavioral problems in adults. Long-term correlates and theoretical conceptualizations of these sequelae are described. PMID- 7870015 TI - Posttraumatic stress disorder in victimization-related trauma. AB - Symptom manifestations of posttraumatic stress disorder (PTSD) are explained in light of current research findings. Assessment methods for evaluating PTSD and trauma exposure are presented and implications for treatment are discussed. PMID- 7870016 TI - Assessing adult victims of interpersonal violence. AB - The assessment of the impacts of interpersonal violence on the client is an important therapeutic process that is likely to improve the quality of care provided by the clinician. Such assessment must, however, be based on an understanding of the logical consequences of violence on the victim's psyche. Additionally, the evaluator must be aware of the theoretical orientation, item content, intended use, and normative data available for the instruments used in any evaluation process. Based on available clinical and research data, trauma specific measures are likely to be more helpful in providing relevant clinical information on the psychological status of victims of violence than are more generic measures of psychological distress. PMID- 7870017 TI - Treating child victims of sexual abuse. PMID- 7870018 TI - Treatment of adult victims of rape. AB - Literature regarding the aftermath of rape, the process of recovery from rape, and treatment is reviewed. Suggestions for conceptualizing a rape experience within the broader context of women's lives are given and specific intervention techniques are also reviewed. PMID- 7870019 TI - Assessing and treating battered women: a clinical review of issues and approaches. AB - Effective assessment and treatment of battered women involves a recognition of the many individual and systemic variables involved. This chapter summarizes the major theoretical positions and research findings and addresses their implications for treatment. PMID- 7870020 TI - Treating survivors of child sexual abuse: a strategy for reintegration. AB - Sexual abuse survivors often present with a complex and changing symptom picture in which posttraumatic reactions are superimposed on an underlying personality disorder, a combination that makes the establishment of a secure therapeutic relationship difficult. An eclectic blend of principles and techniques is recommended in order to address both aspects of the survivor's disturbance. PMID- 7870021 TI - Diphtheria epidemic--New Independent States of the former Soviet Union, 1990 1994. AB - Although diphtheria was controlled for approximately 30 years after the institution of childhood vaccination with diphtheria toxoid in the late 1950s, epidemic diphtheria has reemerged in the New Independent States (NIS) of the former Soviet Union (1,2) (Figures 1 and 2). The epidemic began in 1990 in the Russian Federation and spread to Ukraine in 1991 and, during 1993-1994, to 12 of the 13 remaining NIS. In most affected countries, the incidence rate of reported diphtheria has increased twofold to 10-fold each year. This report summarizes data provided to the World Health Organization (WHO) about diphtheria in the NIS during 1989-1994.* PMID- 7870022 TI - Occupational lead surveillance--Taiwan, July-December 1993. AB - Lead poisoning has been recognized as an occupational disease for centuries and has been linked with both severe and subtle health damage (1-3). In July 1993, the government of Taiwan initiated a compulsory system* for surveillance of elevated blood lead levels (BLLs) among workers in that country (4). All lead exposed workers in lead-using factories are identified and included in the lead surveillance system. This report summarizes findings from this program for July December 1993. PMID- 7870023 TI - Update: dracunculiasis eradication--Ghana and Nigeria, 1994. AB - The plan for the global eradication of dracunculiasis (i.e., Guinea worm disease) was developed in October 1980 (1). Since 1987-1988, Global 2000, Inc., the United Nations Children's Fund (UNICEF), and the U.S. Agency for International Development have assisted the Guinea Worm Eradication Programs in Ghana and Nigeria, countries in west Africa. In 1989, Ghana and Nigeria ranked first and second in the number of reported cases of dracunculiasis with 179,556 and 640,008 cases, respectively (2). This report summarizes data for the two countries during 1994 and describes efforts toward eradication of dracunculiasis. PMID- 7870024 TI - Escherichia coli O157:H7 outbreak linked to commercially distributed dry-cured salami--Washington and California, 1994. AB - From November 16 through December 21, 1994, a total of 20 laboratory-confirmed cases of diarrhea caused by Escherichia coli O157:H7 were reported to the Seattle King County Department of Public Health (SKCDPH). In comparison, three cases were reported during October 1994. Epidemiologic investigation linked E. coli O157:H7 infection with consumption of a commercial dry-cured salami product distributed in several western states. Three additional cases subsequently were identified in northern California. This report summarizes preliminary findings from the outbreak investigation. PMID- 7870025 TI - Emergency department surveillance for weapon-related injuries--Massachusetts, November 1993-April 1994. AB - During 1992, a total of 37,776 firearm-related deaths occurred in the United States (1), and in 1991, firearm-related deaths were the leading or second leading cause of injury death in 15 states (2). Because of limitations in data, however, the epidemiology of nonfatal firearm- and other weapon-related injuries has not been well characterized. To improve characterization of these problems, in 1989, the Massachusetts Department of Public Health (MDPH) began a pilot project to develop the first emergency-department-based statewide Weapon-Related Injury Surveillance System (WRISS) in the United States (3). All 85 hospital emergency departments in Massachusetts (1990 population: 6,016,425) now participate in this system. This report summarizes results from the first 6 months of statewide reporting (November 1993-April 1994), including previously unavailable statewide morbidity data on gunshot and stabbing injuries. PMID- 7870026 TI - HIV counseling and testing--United States, 1993. AB - Counseling and testing (CT) are important components of state and local human immunodeficiency virus (HIV)-prevention programs (1). Analysis of national data sources indicates that HIV-antibody tests are obtained from a variety of testing sites, including private physicians, hospitals, and outpatient clinics (66.7%), and publicly funded sites (33.1%) (2). This report uses data from CDC's 1993 Behavioral Risk Factor Surveillance System (BRFSS) to examine variations in rates of use of private and public HIV CT sites by state. PMID- 7870027 TI - Novel properties of homomeric beta 1 gamma-aminobutyric acid type A receptors: actions of the anesthetics propofol and pentobarbital. AB - In this study we determined the influence of gamma-aminobutyric acid (GABA)A receptor subunit composition on the direct effects of the general anesthetics propofol, pentobarbital, and alphaxalone, using recombinant receptors expressed in Xenopus oocytes. cDNAs coding for human beta 1, alpha 1 beta 1, or alpha 1 beta 1 gamma 2S GABAA receptor subunits were injected into Xenopus oocytes, and responses induced by either GABA or anesthetics were measured by two-electrode voltage-clamp recording. Expression of homomeric beta 1 receptors resulted in the formation of a Cl- channel that was sensitive to picrotoxin and strychnine and could be activated, albeit with relatively low potency, by GABA. However, GABA induced currents of homomeric beta 1 receptors were completely insensitive to the GABAA receptor antagonist bicuculline. Homomeric beta 1 receptors showed marked direct activation by propofol or pentobarbital, but not by alphaxalone. In contrast, these three anesthetics induced much weaker direct activation of Cl- currents in oocytes expressing alpha 1 beta 1 or alpha 1 beta 1 gamma 2S receptors. These data indicate that the beta 1 subunit of the GABAA receptor forms a functional Cl- channel that contains sites for the direct activating effects of GABA, propofol, and pentobarbital and this GABA site is not blocked by bicuculline. PMID- 7870028 TI - Multiple regions of G alpha 16 contribute to the specificity of activation by the C5a receptor. AB - The C5a chemoattractant factor receptor, when expressed in COS-7 cells, can stimulate phosphoinositide-specific phospholipase C activity through the activation of the G16 isoform of the heterotrimeric G protein, but not through the G11 isoform. To identify the regions of the G alpha 16 subunit protein that are responsible for its activation by the C5a receptor, a series of chimeras between G alpha 16 and G alpha 11 were constructed and tested for their ability to be activated by the C5a receptor. Co-transfection experiments with chimeras in which the carboxyl-terminal regions of G alpha 11 were replaced with the corresponding regions of G alpha 16 demonstrated that changes in the carboxyl terminus, e.g., replacement of 134 amino acids, were not sufficient to confer receptor specificity. An additional segment encompassing residues 220-240 of G alpha 16 was required to confer C5a-induced activation. Testing of a reciprocal series of chimeras composed of G alpha 16 sequences at the amino terminus and G alpha 11 sequences at the carboxyl terminus revealed that certain sequences extending from the amino terminus to amino acid 209 of G alpha 16 were sufficient to endow the chimera with much of the specificity for C5a-induced activation. These results suggest that receptor specificity may involve specific conformations of the G protein stabilized by concerted interactions of multiple amino acid sequences distributed throughout the G alpha protein. PMID- 7870029 TI - Agonist-dependent phosphorylation of human muscarinic receptors in Spodoptera frugiperda insect cell membranes by G protein-coupled receptor kinases. AB - Agonist-dependent phosphorylation of G protein-coupled receptors (GPRs) by G protein-coupled receptor kinases (GRKs) is proposed to be a key event initiating homologous receptor desensitization. A technical limitation hindering identification of GPRs as GRK substrates has been the necessity to use purified and reconstituted receptors in GRK assays. Here, the human m2 and human m3 (hm3) muscarinic cholinergic receptors (mAChRs), which couple to attenuation of adenylyl cyclase and stimulation of phospholipase C, respectively, were expressed in Spodoptera frugiperda insect cells and an in vitro approach to studying GPR phosphorylation by GRKs in crude membranes was developed. The m2 mAChR, a known substrate of certain GRKs, was used to validate the approach. The GRK isoform beta-adrenergic receptor kinase (beta ARK)1 phosphorylated the membrane-bound human m2 mAChRs in an agonist-dependent manner. The results demonstrated that endogenous membrane-bound beta gamma subunits of G proteins stimulated the phosphorylation of the membrane-bound m2 mAChR. To reveal new GRK substrates, we tested the expressed hm3 mAChRs. The membrane-bound hm3 mAChRs were phosphorylated by beta ARK1 in an agonist-dependent, G beta gamma-enhanced manner. This is the first demonstration that hm3 mAChRs can serve as substrates for GRKs. The stoichiometry of receptor phosphorylation was approximately 2 mol of phosphate/mol of receptors in the absence of G beta gamma and approximately 4 mol of phosphate/mol of receptors upon addition of G beta gamma. When the specificity of various GRKs towards mAChRs was assessed, beta ARK2 phosphorylated the agonist-activated hm3 mAChRs as efficiently as did beta ARK1; however, neither GRK5 nor GRK6 significantly phosphorylated the hm3 mAChRs under similar conditions. The approach of studying GRK-mediated phosphorylation of GPRs in their membrane-bound state identified the hm3 mAChRs as new substrates for GRKs. This approach should be valuable in identifying other new substrates of GRKs and should aid in studies that elucidate GRK/GPR pairing. PMID- 7870030 TI - The class III antiarrhythmic drug amiodarone directly activates pertussis toxin sensitive G proteins. AB - The class III antiarrhythmic drugs amiodarone and bretylium tosylate are cationic/amphiphilic, and various substances with these physico-chemical properties are known to directly activate heterotrimeric regulatory G proteins. We asked the question of whether class III antiarrhythmic drugs are also direct G protein activators, using HL-60 leukemic cells and purified bovine brain G proteins as model systems. In HL-60 cell membranes, aminodarone increased high affinity GTP hydrolysis with an EC50 of 7.5 microM. The stimulatory effect of amiodarone on GTP hydrolysis was inhibited by pertussis toxin. Amiodarone stimulated binding of guanosine-5'-O-(3-thio)triphosphate to, and incorporation of GTP azidoanilide into, Gi protein alpha subunits in HL-60 membranes. The drug increased the cytosolic Ca2+ concentration in HL-60 cells in the presence but not in the absence of extracellular Ca2+. Amiodarone-induced increases in the cytosolic Ca2+ concentration were reduced by pertussis toxin and by a blocker of non-selective cation channels, SK&F 96365. Amiodarone activated the GTPase of reconstituted Gi/G(o) proteins and G12 with EC50 values of 20 microM and 50 microM, respectively. Bretylium tosylate did not increase GTP hydrolysis in HL-60 membranes or with Gi/G(o) proteins. Our data suggest that amiodarone but not bretylium tosylate is a direct activator of Gi and G(o) proteins and that amiodarone activates nonselective cation channels in HL-60 cells via Gi proteins and independently of Ca2+ mobilization from intracellular stores. Future studies will have to test the hypothesis that direct G protein activation by amiodarone contributes to its toxic and/or therapeutic effects. PMID- 7870031 TI - Welwitindolinone analogues that reverse P-glycoprotein-mediated multiple drug resistance. AB - Welwitindolinones are a family of novel alkaloids recently isolated from the blue green alga Hapalosiphon welwitschii as a part of our effort to identify new compounds that overcome multiple drug resistance. The abilities of three structurally similar members of this family to interact with P-glycoprotein have been compared. Similarly to the effects of verapamil, N-methylwelwitindolinone C isothiocyanate (compound 1) attenuated the resistance of MCF-7/ADR cells to natural product anticancer drugs, including vinblastine, taxol, actinomycin D, daunomycin, and colchicine, without affecting the cytotoxicity of cisplatin. These effects of compound 1 were apparent at doses as low as 0.1 microM, indicating that it is considerably more potent than verapamil for reversal of resistance. Welwitindolinone C isothiocyanate (compound 3) demonstrated weaker reversing activity, whereas an analogue of compound 1 in which the isothiocyanate group is replaced by an isonitrile group (compound 2) was inactive. The accumulation of [3H]vinblastine in SK-VLB-1 cells was increased by compound 1 > compound 3 > verapamil >> compound 2. Interestingly, only compound 1 and verapamil enhanced [3H]taxol accumulation by these cells. Photoaffinity labeling of P-glycoprotein with [3H]azidopine in membranes from SK-VLB-1 cells was inhibited by compounds 1 and 3, but not by compound 2. Therefore, the differences in the size and/or the electronegativity of the isothiocyanate and isonitrile moieties appear to dramatically affect the abilities of the compounds to interact with P-glycoprotein. PMID- 7870033 TI - Differential regulation by anti-tumor-promoting 12-deoxyphorbol-13-phenylacetate reveals distinct roles of the classical and novel protein kinase C isozymes in biological responses of primary mouse keratinocytes. AB - 12-Deoxyphorbol-13-phenylacetate (dPP) is the prototype for a new class of phorbol derivatives that function as protein kinase C (PKC) activators with potent anti-tumor-promoting activity. To explore the mechanism of action of dPP, we have conducted detailed analyses of the translocation and down-regulation patterns of individual PKC isozymes in mouse primary keratinocytes upon dPP treatment. PKC-alpha, -delta, and -epsilon were very quickly (within 2-5 min) translocated from the soluble fraction to the Triton X-100-soluble particulate fraction. PKC-delta and -epsilon were translocated with 2 orders of magnitude higher potency than was PKC-alpha. After translocation, PKC-alpha, -delta, -eta, and -epsilon were down-regulated; the down-regulation of PKC-epsilon contrasts with its retention after phorbol-12-myristate-13-acetate or bryostatin treatment. As was the case with translocation, dPP down-regulated the novel PKC isozymes (delta, epsilon, and eta) with 2 orders of magnitude higher potency (ED50, about 1-2 nM), compared with PKC-alpha (ED50, about 100 nM). dPP induced transglutaminase activity, ornithine decarboxylase activity, and cornification with potencies similar to that for PKC-alpha translocation. On the other hand, dPP caused inhibition of EGF binding with a potency similar to that for the translocation of the novel PKC isozymes. Although the generality of its selectivity in different cell types remains to be determined, at least in keratinocytes dPP is a powerful tool for dissecting the involvement of the classical and novel PKC isozymes in biological responses. The unique regulatory pattern of PKC-epsilon could contribute to the anti-tumor-promoting activity of dPP. PMID- 7870032 TI - Activation of muscarinic cholinergic receptors blocks apoptosis of cultured cerebellar granule neurons. AB - We have recently reported that the majority of cultured rat cerebellar granule neurons undergo apoptosis when maintained in the presence of physiological concentrations of K+ (nondepolarizing conditions). We now report that exposure of cultured cerebellar granule neurons, maintained under nondepolarizing conditions, to the muscarinic cholinergic receptor (mAchR) agonists carbachol and muscarine results in a concentration- and time-dependent inhibition of apoptosis. The nicotinic cholinergic receptor agonist (-)-nicotine fails to mimic, and the nicotinic cholinergic receptor antagonist dihydro-beta-erythroidine fails to antagonize, the survival-promoting effects of carbachol. In contrast, relatively low concentrations of atropine completely prevent the effects of carbachol in blocking apoptotic death of cultured granule neurons. Although the m1- and m2 preferring mAchR antagonists pirenzepine and gallamine, respectively, fail to reverse the effects of carbachol, the m3-preferring antagonist 4-diphenylacetoxyl N- methylpiperidine methiodide completely blocks the survival-promoting effects of carbachol. These data demonstrate that activation of the mAchR (possibly of the m3 subtype) blocks apoptosis of cultured cerebellar granule neurons. The antiapoptotic effects of mAchR agonists are not indirectly mediated via glutamate release from granule neurons, because antagonists of either N-methyl-D-aspartate or non-N-methyl-D-aspartate glutamate receptors fail to affect the antiapoptotic effects of carbachol or muscarine. Moreover, exposure of cultured cerebellar granule neurons to antiapoptotic concentrations of carbachol, in contrast to high concentrations of K+ or glutamate receptor agonists, results in only a small and transient elevation of the intracellular Ca2+ concentration, as measured by fura 2 microfluorimetry. Slow neurotransmitters such as acetylcholine, acting via their cognate G protein-coupled receptors, may prevent neuronal apoptosis in the developing (and perhaps adult) central nervous system. PMID- 7870034 TI - Identification and characterization of endothelin receptors on rat osteoblastic osteosarcoma cells: down-regulation by 1,25-dihydroxy-vitamin D3. AB - Endothelins (ETs) (ET-1, ET-2, and ET-3), a family of 21-amino acid peptides, mediate a host of biological responses by binding to specific cell surface receptors termed ETA and ETB. Because a role for ET in bone remodeling has been suggested, the present study was undertaken (a) to characterize ET receptors and their responses in the rat osteosarcoma cell line ROS 17/2.8 and (b) to study their regulation by 1,25-dihydroxy-vitamin D3. Binding studies using 125I-ET-1 (a nonselective agonist) and 125I-IRL-1620 (an ETB receptor-selective agonist) indicated that these cells display high affinity ETA and ETB receptors in the ratio of 3:1. Addition of ET-1 or sarafotoxin 6c to myo-[3H]inositol-labeled cells resulted in an increase in inositol phosphate accumulation as well as in intracellular Ca2+ release, suggesting that these receptors are coupled to phospholipase C. In addition, ET-1 but not sarafotoxin 6c induced a modest increase in the expression of osteocalcin protein that was completely blocked by BQ123 (an ETA receptor-selective antagonist), indicating that activation of ETA receptors plays a role in the induction of osteocalcin. Treatment of ROS osteoblasts with 10 nM 1,25-dihydroxy-vitamin D3 for 14 hr resulted in a significant (> 50%) decrease in 125I-ET-1 and 125I-IRL-1620 binding. This decrease in binding was shown to be due to a decrease in the number of ET receptors, with no change in affinity. Although both ETA and ETB receptors were down-regulated in response to 1,25-dihydroxy-vitamin D3, only ETA receptor mRNA levels were significantly decreased, with very little change in ETB mRNA levels. These data indicate that ROS osteoblasts display both ETA and ETB receptors that are functional. Induction of osteocalcin was primarily mediated by ETA receptors, and these receptors were also down-regulated at the mRNA level by 1,25-dihydroxy vitamin D3. PMID- 7870035 TI - Differential in vivo induction of immediate early genes by oxotremorine in the central nervous system of long- and short-sleep mice. AB - Long-sleep (LS) and short-sleep (SS) mice show differential sensitivity to both acute and chronic ethanol administration. Previous data also showed differential behavioral responses to muscarinic acetylcholine receptor agonist or antagonist treatment. We now report significantly greater inductions of c-fos, c-jun, jun-B, and Egr-1, but not jun-D, mRNA in the central nervous system (CNS) of LS versus SS mice after the intraperitoneal administration of oxotremorine. These genomic responses were dose dependent and completely inhibited (in both strains) by scopolamine, a specific muscarinic receptor antagonist. In situ hybridization studies verified the greater immediate early gene (IEG) inductions in LS mice, as initially observed by Northern analysis, and specifically showed that c-fos mRNA induction occurred predominantly in the thalamus, olfactory bulb, cerebellum, and cerebral cortex. Oxotremorine-induced c-jun mRNA was increased in cerebellum, CA1 hippocampal field, and cerebral cortex of both strains. Induced jun-B and Egr-1 transcripts were determined to have very similar CNS distribution patterns. Both mRNA species were induced in the cerebral cortex, caudate nucleus and putamen, hippocampal structures, and olfactory bulb. To further determine whether these differential IEG inductions reflect regional differences in receptor numbers, we determined the distributions and levels of each of the five muscarinic receptor subtypes in both strains by in situ hybridization. These data show that differences in receptor numbers alone may not account for the differential IEG inductions observed between the strains. Differential coupling constraints among CNS muscarinic receptors in LS versus SS mouse CNS may also play a significant role in producing differential IEG inductions. PMID- 7870036 TI - Selective antagonist for the cerebellar granule cell-specific gamma-aminobutyric acid type A receptor. AB - Numerous ligands affect inhibitory gamma-aminobutyric acid (GABA)A receptors, none of them showing strict receptor subtype specificity. We report here that a cerebellar GABAA receptor subtype can be uniquely modulated by furosemide but not by bumetanide, another Cl-/cation transport blocker. Furosemide specifically reversed the inhibition by GABA of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding in the cerebellar granule cell layer, as detected by autoradiography of rat brain sections. With recombinant receptors expressed in Xenopus oocytes, furosemide antagonized potently (IC50, about 10 microM), rapidly, and reversibly GABA-evoked currents of cerebellar granule cell-specific alpha 6 beta 2 gamma 2 receptors but not alpha 1 beta 2 gamma 2 receptors (IC50, > 3 mM). Furosemide reversed GABA inhibition of [35S]TBPS binding and elevated basal [35S]TBPS binding only with alpha 6 beta 2 gamma 2 and alpha 6 beta 3 gamma 2 receptors and not with alpha 6 beta 1 gamma 2 or alpha 1 beta 1/2/3 gamma 2 receptors. It appeared to interact with the receptor complex via a novel recognition site that allosterically regulates the Cl- ionophore. Furosemide is the first subtype-selective GABAA receptor (alpha 6 beta 2/3 gamma 2) antagonist and should facilitate studies on cerebellar physiology. It might serve as a prototypic structure for the development of additional subtype-selective GABAA ligands. PMID- 7870037 TI - In vitro transcription termination by N,N'-bis(2-chloroethyl)-N-nitrosourea induced DNA lesions. AB - N,N'-Bis(2-chloroethyl)-N-nitrosourea (BCNU) and its derivatives are chemotherapeutic DNA-damaging agents that generate a variety of monoadducts, intrastrand cross-links, and interstrand cross-links. The cytotoxic potential of the compounds has been linked to their ability to form DNA interstrand cross links, which presumably inhibit subsequent DNA replication. To address the possibility that BCNU-induced lesions may also influence other DNA-directed actions such as transcription, and to identify the DNA lesions involved, a synthetic DNA template containing phage RNA polymerase promoters at both ends was incubated with BCNU and, after drug removal, transcribed in vitro. For comparison, similar studies were carried out with cis-diammine dichloroplatinum(II) and trans-diamminedichloroplatinum(II), which are known to induce defined transcription-terminating lesions. The results suggest that BCNU, like platinum compounds, can induce lesions resulting in termination of transcription in vitro, although the predominant transcription-terminating lesions, unlike those produced by cis-diamminedichloroplatinum(II), most likely represent interstrand DNA cross-links. PMID- 7870038 TI - Induction of cytochrome P4501A1 by aryl hydrocarbon receptor agonists in porcine aorta endothelial cells in culture and cytochrome P4501A1 activity in intact cells. AB - Endothelium is a single-cell layer lining blood vessels and constituting capillaries and could be a primary site of chemical effects in the cardiovasculature and systemically. Cytochrome P4501A1 (CYP1A1) is strongly inducible in vertebrate endothelium in vivo by aryl hydrocarbon receptor (AhR) agonists [Mol. Pharmacol. 36:723-729 (1989); Mol. Pharmacol. 41:1039-1046 (1992)]. We investigated CYP1A expression and activity in porcine aorta endothelial cells (PAEC) exposed in culture to the AhR agonists 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4'-tetrachlorobiphenyl (TCB), benzo[a]pyrene (BP), or beta-naphthoflavone (BNF). Immunoblotting with monoclonal anti-CYP1A1 and polyclonal anti-CYP1A1 and anti-CYP1A2 antibodies showed that CYP1A1 was induced in cultures exposed to TCDD, TCB, BP, or BNF but was not detectable in untreated or dimethylsulfoxide-exposed cultures. CYP1A1 was strongly induced at intermediate concentrations (0.1 microM or 1.0 microM) of TCB, BP, or BNF, but induction was suppressed by higher concentrations, a response not due to general toxicity; cell viability (trypan blue exclusion) was > 97% with BNF or TCB at up to 10 microM. CYP1A1 induction by TCDD was maximal at 0.3-1.0 nM. ED50 values for induction of CYP1A1 by TCDD, TCB, and BP were 0.016 nM, 3-10 nM, and 180 nM, respectively. Immunohistochemical analysis confirmed CYP1A1 induction in PAEC but also showed that only some cells in the cultures were induced. Subcellular fractionation, marker enzyme analysis, and immunoblot analysis showed that PAEC had a typical complement of microsomal electron transport components. NADPH-cytochrome P450 reductase showed comparable rates (approximately 40 nmol/min/mg) in induced and control cultures. Cultures maximally induced by 0.1 microM TCB had microsomal CYP1A1 [ethoxyresorufin-O deethylase (EROD)] activity averaging 25 pmol/min/mg. Addition of purified rat reductase to PAEC microsomes increased the EROD rates 3-fold. EROD rates measured in intact cells maximally induced by BP, TCB, or TCDD ranged from 15 to 30 pmol/min/mg of whole-cell protein. Methoxyresorufin O-demethylase activity induced by TCDD was 2 pmol/min/mg, i.e., < 10% of the EROD activity. In cultures in which CYP1A1 was strongly induced, CYP1A2 was not detectably expressed. The CYP1A2 inducer acenaphthylene did not induce EROD or methoxyresorufin O demethylase in intact cells. The results show that CYP1A1 but not CYP1A2 is strongly induced in mammalian endothelial cells in culture and that CYP1A1 is active in intact cells, although the catalytic rates are low.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7870039 TI - Characterization of two affinity states of adenosine A2a receptors with a new radioligand, 2-[2-(4-amino-3-[125I]iodophenyl)ethylamino]adenosine. AB - Adenosine analogs substituted in the 2-position with arylamino groups have been found to have high affinity and selectivity for A2a adenosine receptors. Two such compounds, 2-[2-(4-aminophenyl)ethylamino]adenosine and 2-[2-4-amino-3 iodophenyl)ethylamino]adenosine (I-APE), were synthesized and found to be potent coronary vasodilators (ED50 < 3 nm). These compounds bind weakly to A1 adenosine receptors of rat cortex (Ki > 150 nM). 125I-APE was synthesized and the new radioligand was found to bind to two affinity states of rat striatal A2a adenosine receptors (Kd = 1.3 +/- 0.1 nM and 19 +/- 4.5 nM). The high affinity site represents a previously unrecognized small (15-20%) fraction of A2a adenosine receptors coupled to G proteins. Guanosine 5'-O-(3-thio)triphosphate (GTP gamma S) reduces specific binding of 125I-APE half-maximally at a concentration of 45 +/- 2 nM. [3H]CGS21680 also binds to two affinity states of A2a receptors on striatal membranes (Kd = 3.9 +/- 0.9 and 51 +/- 5.5 nM), although in previous studies single Kd values ranging from 5 to 15 nM have been reported. This high affinity site is substantiated by the finding that the IC50 of CGS21680 in competition with 125I-APE binding to striatal membranes is shifted leftward in membranes diluted for 4 min before filtration, to selectively dissociate radioligand from low affinity receptors. Assuming that agonist radioligands bind to both coupled and uncoupled forms of striatal A2a adenosine receptors, we could simulate with the computer the finding that the decrease in specific binding induced by GTP gamma S (100 microM) is variable and depends on radioligand concentration, ranging from 20 to 90%. Unlike 125I-APE, [3H]CGS21680 is charged at physiological pH, and treatment of membranes with the pore-forming antibiotic alamethicin uncovers cryptic [3H]CGS21680 but not 125I-APE binding sites. We conclude that the GTP gamma S-sensitive high affinity form of the A2a adenosine receptor can be preferentially labeled by 125I-APE, due to both its high specific activity and its physicochemical properties. Possible functional manifestations of poor coupling of A2a adenosine receptors to G proteins are discussed. PMID- 7870040 TI - Functional coupling of the beta 2-adrenoceptor to a pertussis toxin-sensitive G protein in cardiac myocytes. AB - Recently we demonstrated that the effects of beta 2-adrenoceptor (AR) stimulation to augment Ca2+ current (ICa), cytosolic Ca2+ (Cai) transients, and contractility in rat ventricular myocytes are largely dissociated from its effect to increase cellular cAMP levels. This result suggested that beta 2ARs might be coupled to signaling pathways other than the Gs alpha-mediated activation of adenylyl cyclase. Here we show that pertussis toxin (PTX) pretreatment specifically potentiates the responses of rat heart cells to beta 2AR but not beta 1AR stimulation. After PTX pretreatment, 1) the dose-response curve for the effects of the beta 2AR agonist zinterol on contraction amplitude is shifted leftward and upward (EC50 changed from about 1.0 microM to 70 nM), 2) in indo-1-loaded cells, the maximal effects of zinterol (10(-5) M) on Cai transient and contraction amplitudes are additionally increased 1.7- and 2.0-fold, respectively, over those in control cells, and 3) the increase in ICa amplitude induced by the same zinterol concentration is potentiated by 2.5-fold. Similar effects of PTX are observed when beta 2ARs are stimulated by isoproterenol in the presence of a selective beta 1AR blocker, CGP 20712A. All effects of beta 2AR agonists in both PTX-treated and control cells are abolished by a selective beta 2AR blocker, ICI 118,551. In contrast, neither the base-line ICa, Cai transient, and contraction in the absence of beta AR stimulation nor the beta 1AR-mediated augmentations of these parameters are significantly altered by PTX treatment. These results demonstrate, for the first time, that the Gs-coupled beta 2AR can simultaneously activate a pathway that leads to functional inhibition in cardiac cells via a PTX sensitive G protein. The activation of more than one G protein during beta 2AR stimulation, leading to functionally opposite effects, may provide a mechanism to protect the heart from Ca2+ overload and arrhythmias during the response to stress. PMID- 7870041 TI - Characterization of cyclic nucleotide phosphodiesterases with cyclic GMP analogs: topology of the catalytic domains. AB - To help define essential interactions of cGMP with the catalytic site, we tested a series of cGMP analogs as competitive inhibitors of each cyclic nucleotide phosphodiesterase (PDE) family known to hydrolyze cGMP (PDE1, PDE2, PDE3, PDE5, and PDE6). IC50 values, relative to cGMP, were used to predict which functional groups of cGMP contribute to binding by the catalytic sites of each isozyme. The results indicate that the N1-nitrogen of cGMP contributes to binding at the catalytic site of all PDEs, probably as a hydrogen donor. All PDEs tested, with the exception of PDE2, also use the 6-oxo group, probably as a hydrogen acceptor. In contrast to other cGMP-binding enzymes, the 2-amino and 2'-hydroxyl groups of cGMP are not major requirements for binding to any PDE. The 8-bromo- and 8-p chlorophenylthio-substituted analogs inhibit PDE1, PDE2, and PDE6 activity with high relative affinities, suggesting that these PDEs are not sterically hindered with bulky 8-position substitutions and that they do not preferentially bind the anti-conformation of cGMP. PDE3 and PDE5 have reduced apparent affinity for these analogs and therefore either are sterically hindered with these substitutions or bind cGMP in the anti-conformation. Overall, the data show substantial differences in structural requirements for cGMP binding to the catalytic sites of the different PDE families. Comparisons with published data show different structural requirements for binding to the catalytic, compared with noncatalytic, binding domains of PDEs. Even larger differences are seen between the requirements for binding to PDE catalytic sites and those for the cGMP-dependent protein kinase and the cGMP-gated cation channel. PMID- 7870042 TI - Characterization of cyclic nucleotide phosphodiesterases with cyclic AMP analogs: topology of the catalytic sites and comparison with other cyclic AMP-binding proteins. AB - To define essential interactions of cAMP with the catalytic sites of cyclic nucleotide phosphodiesterases (PDEs) and to begin to map the topology of the sites, we have tested a series of cAMP analogs as competitive inhibitors of the PDEs that hydrolyze cAMP with high efficiency (PDE1, PDE2, PDE3, and PDE4). Comparisons of IC50 values, relative to cAMP, were used to predict which functional groups on cAMP interact with each isozyme. Common to all PDEs tested, except for the calcium/calmodulin-dependent PDE (CaM-PDE, PDE1), is an interaction at the N1-position of cAMP and a distinct lack of binding to the 2' hydroxyl group of the ribose moiety. Only the cGMP-stimulated (PDE2) and cAMP specific (PDE4) PDEs appear to interact strongly at the N7-position. The cGMP inhibited PDE (cGI-PDE, PDE3) may interact less strongly with this nitrogen. The PDE4 and PDE3 both interact with cAMP through the 6-amino group, which most likely serves as a hydrogen bond donor. PDE4 and PDE3 appear to be able to bind to the anti-conformer of cAMP, whereas the PDE1 and PDE2 bind the syn-conformer. The CaM-PDE exhibits no appreciable specificity for any of the analogs tested, showing little or no interaction with the 6-amino group or with any of the ring nitrogens. Large differences exist in the nucleotide-binding requirements for the PDE catalytic sites, compared with the regulatory sites of cAMP-dependent protein kinase and the catabolite activator protein. PMID- 7870043 TI - Characterization of presynaptic calcium channels with omega-conotoxin MVIIC and omega-grammotoxin SIA: role for a resistant calcium channel type in neurosecretion. AB - The peptide Ca2+ channel antagonists omega-conotoxin (omega-CTX) MVIIC and omega grammotoxin (omega-GTX) SIA were studied by measuring their effects on the release of [3H]glutamate from rat brain synaptosomes. The pseudo-first-order association constant for omega-CTX MVIIC (1.1 x 10(4) M-1 sec-1) was small, relative to that for omega-GTX SIA (3.6 x 10(5) M-1 sec-1). Equilibrium experiments showed that omega-CTX MVIIC blocked approximately 70% of Ca(2+) dependent glutamate release evoked by 30 mM KCl (IC50 approximately 200 nM), whereas omega-GTX SIA virtually eliminated release, with lower potency (IC50 approximately 700 nM). At stronger depolarizations (60 mM KCl), neither toxin (at 1 microM) showed significant block of release, but when these or other Ca2+ channel antagonists (omega-CTX GVIA or omega-agatoxin IVA) were used in combination a substantial fraction of release was blocked. [3H]Glutamate release that was resistant to omega-CTX MVIIC was characterized with respect to its sensitivity to block by omega-GTX SIA and the inorganic blocker Ni2+. Both omega GTX SIA and Ni2+ were relatively weak blockers of the resistant release. These results suggest that a previously uncharacterized Ca2+ channel exists in nerve terminals and can be distinguished on the basis of its resistance to omega-CTX MVIIC and its weak sensitivity to omega-GTX SIA and Ni2+. Thus, at least three channel types (P, N, and a "resistant" type) contribute to excitation-secretion coupling in nerve terminals. PMID- 7870044 TI - Selective actions of certain neuroactive pregnanediols at the gamma-aminobutyric acid type A receptor complex in rat brain. AB - Certain endogenous pregnanediols (5 alpha-pregnan-3 alpha,20 alpha-diol and 5 beta-pregnan-3 alpha,20 beta-diol) were observed to have limited efficacy as allosteric modulators of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) and [3H]flunitrazepam binding to sites on the gamma-aminobutyric acid (GABA)A receptor complex in rat brain. In contrast, 3 alpha-hydroxy-5 alpha-pregnan-20 one (3 alpha,5 alpha-P) and 3 alpha-hydroxy-5 beta-pregnan-20-one (3 alpha,5 beta P) have full efficacy. Moreover, 3 alpha,5 beta-P but not 3 alpha,5 alpha-P recognizes high (nanomolar) and low (micromolar) affinity neuroactive steroid sites in these allosteric modulatory assays. The concentration-response curve for 3 alpha,5 alpha-P modulation of [35S]TBPS binding was shifted rightward in the presence of these pregnanediols and GABA. The maximum shift produced by these pregnanediols never exceeded the concentration-response curve obtained with 3 alpha,5 alpha-P alone in the absence of GABA. Additionally, neither 5 alpha pregnan-3 alpha,20 alpha-diol nor 5 beta-pregnan-3 alpha,20 beta-diol had any effect on the site recognized by 3 alpha,5 alpha-P in the absence of GABA. The difference in the affinities of the two apparent sites (29 nM versus 152 nM in the presence and absence of GABA, respectively) recognized by 3 alpha,5 alpha-P is only approximately 5-fold. In contrast, the difference between the high (30 nM) and low (7 microM) affinity sites discriminated by 3 alpha,5 beta-P is > 200 fold. Thus, the selective interaction between the high affinity site recognized by 3 alpha,5 beta-P and these pregnanediols can be clearly observed. A saturating concentration of 5 beta-pregnan-3 alpha,20 beta-diol selectively eliminated the high affinity component recognized by 3 alpha,5 beta-P, whereas 5 alpha-pregnan-3 alpha,20 alpha-diol did not completely abolish the high affinity site. 5 alpha Pregnan-3 alpha,20 alpha-diol recognized only a portion of the high affinity sites discriminated by 3 alpha,5 beta-P, relative to 5 beta-pregnan-3 alpha,20 beta-diol, whereas the two pregnanediols recognized a similar population of sites mediating 3 alpha,5 alpha-P inhibition of [35S]TBPS binding. Collectively, these studies provide evidence that the limited efficacy of certain pregnanediols as allosteric modulators of [35S]TBPS binding may be explained in part by selectivity for the high affinity site recognized by 3 alpha,5 beta-P.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7870045 TI - Different subunit requirements for volatile and nonvolatile anesthetics at gamma aminobutyric acid type A receptors. AB - The ability of volatile (halothane and isoflurane) and nonvolatile (alphaxalone and pentobarbital) general anesthetics to modulate radioligand binding to gamma aminobutyric acid (GABA)A receptors was examined in an immortalized cell line (WSS-1) expressing rat alpha 1 and gamma 2 subunits. Volatile anesthetics enhance [3H]flunitrazepam binding to WSS-1 cells in a concentration-dependent manner, with potencies and efficacies comparable to those found with native GABAA receptors. Transfection of these cells with cDNAs encoding rat beta 2 or beta 3 subunits had a significant influence on anesthetic efficacy but not potency in this assay. Thus, transfection with the beta 2 subunit reduced the efficacy of both isoflurane and halothane, whereas transfection with the beta 3 subunit increased the efficacy of isoflurane but not halothane, compared with values obtained in WSS-1 cells. In contrast, alpha-xalone (an anesthetic steroid) had no effect, whereas at high concentrations pentobarbital (an anesthetic barbiturate) produced a modest inhibition of [3H]flunitrazepam binding to GABAA receptors in WSS-1 cells. Transfection of WSS-1 cells with cDNAs encoding either beta 2 or beta 3 subunits resulted in a concentration-dependent enhancement of [3H]flunitrazepam binding by these nonvolatile anesthetics. Moreover, pentobarbital was significantly more potent in enhancing [3H]flunitrazepam binding to WSS-1 cells transfected with the beta 2 subunit, compared with the beta 3 subunit. The difference in subunit requirements between volatile and nonvolatile anesthetics for enhancement of [3H]flunitrazepam binding indicates that these classes of agents affect GABAA receptor function at distinct loci. These studies also provide evidence that the beta subunit is required for these nonvolatile anesthetics to positively modulate GABAA receptors. PMID- 7870046 TI - Mechanism of the dopamine-releasing actions of amphetamine and cocaine: plasmalemmal dopamine transporter versus vesicular monoamine transporter. AB - The effects of amphetamine and cocaine were studied in [3H]-dopamine-loaded and superfused COS-7 cells transfected with either the cDNA of the plasmalemmal dopamine transporter ("DAT cells") or the cDNA of the vesicular amine transporter ("VAT cells"), or with both transporters ("DAT/VAT cells"). Amphetamine (0.01-100 microM, added for 4 min of superfusion) led to a concentration-dependent increase in dopamine release in DAT cells, as well as in DAT/VAT cells. The EC50 of the effect of amphetamine on DAT cells was 1.1 +/- 0.6 microM; the effect on DAT/VAT cells did not reach a plateau in the concentration range tested. With longer exposure to amphetamine, dopamine efflux from DAT cells reached a peak and quickly returned to baseline, in spite of the continued presence of the drug, whereas in DAT/VAT cells and in VAT cells the effect was sustained. Cocaine (up to 100 microM) did not exert any effect of its own in DAT cells or VAT cells but inhibited the amphetamine-induced release of dopamine from DAT cells in a competitive manner. In DAT/VAT cells cocaine and its analogue (-)-2 beta carbomethoxy-3 beta-(4-fluorophenyl)tropane caused an efflux of dopamine resembling that caused by amphetamine but quantitatively much smaller. The rank order of potency was the same as in uptake experiments [(-)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane > cocaine]. The effect of cocaine was mimicked by the reduction of chloride. The results indicate that there is a plasmalemmal component and a vesicular component in the dopamine-releasing action of amphetamine. The releasing action of cocaine is dependent on the existence of a vesicular pool of the neurotransmitter and seems to be linked to inhibition of the plasmalemmal dopamine transporter. PMID- 7870047 TI - Identification of amino acids in the N-methyl-D-aspartate receptor NR1 subunit that contribute to the glycine binding site. AB - The mammalian N-methyl-D-aspartate (NMDA) receptor complex is though to consist of an NR1 subunit in combination with one or more of the four NR2 subunits (A, B, C, and D). When corresponding cDNAs are expressed in Xenopus oocytes, ion channels with the characteristic profile of NMDA receptors are formed. The receptor is unique in requiring two coagonists, glutamate and glycine, for activation of the channel. We have used site-directed mutagenesis to study amino acids in the human NR1 subunit that contribute to the glycine binding site of the NMDA receptor without affecting the agonist site for glutamate. Mutations to D481 and K483 produced receptors with up to 160-fold lower affinities for glycine, as well as other agonists and partial agonists, without affecting maximum current size or the degree of agonist efficacy. The D481A mutation also led to 40-50-fold lower affinities for two structurally diverse glycine site antagonists. From these data we propose that the carboxyl group of this aspartate interacts with the amino moiety of glycine and the equivalent group contained in other agonists and antagonists. PMID- 7870048 TI - Time- and voltage-dependent block of delayed rectifier potassium channels by docosahexaenoic acid. AB - Docosahexaenoic acid (22:6n3) acts at an extracellular site to produce a voltage- and time-dependent block of the delayed rectifier current (IK) similar to that classically described for intracellularly applied quaternary ammonia compounds. In dissociated cells from the pineal gland, some long-chain polyunsaturated fatty acids reduced both late sustained (IK) (for 22:6n3, IC50 = 2.5 +/- 0.3 microM) and early transient (IA) (IC50 = 2.0 +/- 0.1 microM) components of potassium current when applied extracellularly, whereas the monounsaturate oleic acid had minimal efficacy. From comparisons of other related fatty acids, it was determined that there is a structural requirement for polyunsaturation to block IK. In contrast, chain-elongated 22-carbon polyunsaturates acted similarly to their precursor 20-carbon fatty acids (arachidonic acid and eicosapentanoic acid). Block of IK by 22:6n3 was accompanied by a dose-dependent acceleration of the current decay in both whole-cell and outside-out membrane patches, and 22:6n3 increased the macroscopic inactivation rate of IA. The combined "eicosanoid" inhibitor eicosatetraenoic acid, when included in the patch pipette, did not antagonize the action of 22:6n3. Instead, eicosatetraenoic acid produced a direct block of IK when applied extracellularly at high concentrations (25 microM). Analyses of voltage- and time-dependent block by 22:6n3 support the hypothesis that certain fatty acids directly interact with and preferentially block the open state of some potassium channels. We also describe an interaction between fatty acid block and zinc; 22:6n3 failed to block either IA or IK in the presence of zinc or cadmium, whereas extracellular calcium did not affect the response. These studies suggest a possible biological function for 22:6n3 in the nervous system, which may underlie its essential role during neural development. PMID- 7870049 TI - A human T lymphoid cell variant resistant to the acyclic nucleoside phosphonate 9 (2-phosphonylmethoxyethyl)adenine shows a unique combination of a phosphorylation defect and increased efflux of the agent. AB - 9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is a new antiviral agent with activity against herpes viruses and retroviruses, including human immunodeficiency virus, but its metabolism and mechanism of action remain unclear. We have isolated a human T lymphoid cell line (CEMr-1) that is resistant to the antiproliferative effects of PMEA. The antiviral effects of PMEA against human immunodeficiency virus-1 infection were also greatly reduced in CEMr-1 cells, compared with the parental cells. This mutant showed cross-resistance to the related acyclic nucleoside phosphonates 9-(2-phosphonylmethoxyethyl)diaminopurine and 9-(2 phosphonylmethoxyethyl)guanine and the lipophilic prodrug bis(pivaloyloxymethyl) 9-(2-phosphonylmethoxyethyl)adenine-( bispome-PMEA), as well as partial resistance to the purine nucleosides 2-chlorodeoxyadenosine, 2-fluro-9-beta-D arabinosylfuranosyladenine, and adenosine, but did not show resistance to 2' deoxyadenosine or 9-beta-D-arabinosylfuranosyladenine. We compared the uptake and metabolism of [3H]PMEA and [3H]-bispom-PMEA in the mutant and parental cells. The analysis of radioactive products by high pressure liquid chromatography revealed marked alterations in the ability of the mutant cell line to accumulate PMEA and its anabolites, compared with the parental cells. Accumulation of PMEA, PMEA monophosphate, and PMEA bisphosphate (major metabolites formed with either PMEA or bispom-PMEA) decreased by 50, 95, and 97%, respectively. Compared with the parental cells, the variant cells showed a approximately 7-fold increase in the rate of efflux of PMEA and a 2-fold decrease in the activity of adenylate kinase. In contrast, other enzymes of nucleotide metabolism, such as adenosine kinase, deoxycytidine kinase, and 5-phosphoribosyl-1-pyrophosphate synthetase, showed no significant change in the two cell lines. Overall, these results suggest that the mutation in this resistant cell line is of a novel type, involving an alteration in the cellular efflux of PMEA as the major basis for the resistant phenotype. PMID- 7870050 TI - Structure-activity relationships of new heterocycle-containing bisphosphonates as inhibitors of bone resorption and as inhibitors of growth of Dictyostelium discoideum amoebae. AB - The mechanisms by which bisphosphonate drugs inhibit osteoclast-mediated bone resorption are unclear. Effects of bisphosphonates on cellular enzymes, metabolic pathways, and osteoclast morphology have previously been described and could culminate in a generalized cytotoxic effect or a decreased capacity of osteoclasts to resorb bone. Recent studies of the structure-activity relationship for the bisphosphonate side chain indicate, however, that at least the newer generations of nitrogen-containing bisphosphonates probably act by binding to a specific target at a site that is complementary in structure to the bisphosphonate side chain. We have previously proposed that such a target for bisphosphonates is also present in amoebae of the cellular slime mold Dictyostelium discoideum, because growth of this microorganism is inhibited by a wide range of bisphosphonates in a manner that closely reflects the antiresorptive potencies of the bisphosphonates in vivo. We have added support for this view by examining the potency towards Dictyostelium of bisphosphonates in which slight changes in the structure of the side chain or conformational restrictions to the side chain have marked effects on antiresorptive potency. The changes in the side chain that affected the in vivo antiresorptive potency of the bisphosphonates consistently affected in a similar manner the potency of the bisphosphonates as inhibitors of the growth of Dictyostelium amoebae. These observations confirm that bisphosphonate drugs have a molecular target that is common to both Dictyostelium amoebae and osteoclasts. PMID- 7870051 TI - Mode of action of iron(III) chelators as antimalarials. III. Overadditive effects in the combined action of hydroxamate-based agents on in vitro growth of Plasmodium falciparum. AB - Hydroxamate-based iron(III) chelators exhibit potent antimalarial effects on the asexual stages of Plasmodium falciparum grown in vitro. Antimalarial activity varies with the parasite growth stage and the drug permeation properties. The hydrophilic drug desferrioxamine (DFO) is ineffective on early stages (ring forms) of the parasite due to its poor permeability but irreversibly blocks the growth of advanced stages of parasites. On the other hand, hydrophobic reversed siderophores (RSFs) are more membrane permeable and affect all parasite developmental stages; they affect ring forms irreversibly and trophozoite/schizont forms reversibly and at relatively faster rates, compared with DFO. These observations have provided the basis for postulating a possible overadditive action of the two, distinctly acting, iron chelator types for enhanced antimalarial activity. This was assessed in this study by using novel fast-acting chelators such as RSF derivatives (RSFleum2 and RSFm2) in combination with the relatively slow-acting DFO. Parasite growth was assessed in terms of nucleic acid synthesis and parasitemia. The results indicate that, at any molar ratios of the two types of drugs, the combined inhibitory effect was faster and more potent than the sum of individual effects. The combined drug action showed neither additive nor independent but overadditive properties, as well as sustained inhibition even after drug removal. The potentiating action of RSFs on the long-lasting effects of DFO on parasite growth conformed with the postulated mechanistic model of iron chelator action and iron handling by parasites. Iron chelator combinations might be of therapeutic value. PMID- 7870052 TI - Oxidative metabolism of lansoprazole by human liver cytochromes P450. AB - The aim of this work was to identify the form(s) of human cytochrome P450 (P450) involved in the hepatic biotransformation of lansoprazole to its two main metabolites, i.e., the sulfone and the hydroxy derivative. In liver microsomes, the production of the sulfone of lansoprazole correlated with the level of P450 3A4, cyclosporin oxidase, and the production of the hydroxy derivative, as well as of omeprazole sulfone. The production of hydroxylansoprazole moderately correlated with the level of P450 3A4, cyclosporin oxidase, and (S)-mephenytoin 4'-hydroxylase. The production of the sulfone and of the hydroxy derivative of lansoprazole was significantly inhibited by anti-P450 3A4 antibodies, by cyclosporin and ketoconazole, and by tolbutamide. Anti-P450 2C8 and 2C3 antibodies moderately inhibited the biotransformation of lansoprazole, whereas they completely inhibited (S)-mephenytoin 4'-hydroxylase activity under the same conditions. In primary cultures of human hepatocytes, the biotransformation of lansoprazole and the oxidation of cyclosporin were strongly increased by rifampicin and phenobarbital, whereas (S)-mephenytoin 4'-hydroxylation was not. beta-Naphthoflavone did not induce the formation of the sulfones but stimulated the production of hydroxylansoprazole. Among several forms of cDNA-expressed human P450s, 3A4 generated significant amounts of the sulfones of lansoprazole and omeprazole and 2C18 was active for the production of hydroxylansoprazole but inactive in the 4'-hydroxylation of (S)-mephenytoin. We conclude that P450 3A4 is the major enzyme involved in the production of the sulfone of lansoprazole and that this P450, as well as P450 2C18 and/or another 2C-related form, could contribute to the production of hydroxylansoprazole. PMID- 7870053 TI - Interaction of flavones and their bromoacetyl derivatives with NAD(P)H:quinone acceptor oxidoreductase. AB - Flavones are a new type of inhibitor of NAD(P)H:quinone acceptor oxidoreductase (DT-diaphorase, EC 1.6.99.2). To further characterize the flavone binding site, three bromoacetyl derivatives of flavones, i.e., 7-bromoacetylflavone, 5-hydroxyl 7-bromoacetylflavone, and 7,8-dibromoacetylflavone, have been synthesized. These compounds have been found to be potent inhibitors that inactivate the rat quinone reductase in a time-dependent manner, suggesting that they can be used as affinity labels for the enzyme. Among the three bromoacetyl derivatives, 7,8 dibromoacetylflavone is the most potent inhibitor; however, its labeling of the quinone reductase is the least stable, so that the enzyme regains activity after a short incubation. In contrast, the inactivation of the quinone reductase by 5 hydroxyl-7-bromoacetylflavone is stable. Accordingly, this flavone derivative is the most suitable compound for labeling the flavone binding site of the enzyme. Electrospray mass spectrometry has been applied to demonstrate that 5-hydroxyl-7 bromoacetylflavone labels this enzyme in a stoichiometric manner. PMID- 7870054 TI - The complete cDNA and deduced amino acid sequence of equine IgE. AB - The cDNA from a transcript encoding the complete heavy chain of the equine immunoglobulin IgE has been cloned and sequenced. A fragment of the equine epsilon gene was amplified from cDNA using PCR and this fragment was then used to probe a horse cDNA library prepared from peripheral blood lymphocytes. A recombinant clone containing the cDNA encoding the complete horse epsilon chain and its associated V-D-J and leader, was subsequently isolated and sequenced. Comparison of the deduced amino acid sequence of equine IgE with the C epsilon heavy chains of other species indicates it to be most similar to human C epsilon (54%), followed by sheep C epsilon (52%); the greatest sequence similarity was found in the C epsilon 3 and C epsilon 4 domains among the species compared. The associated V-region had greatest similarity in FR1 to those reported for sheep and the cow (> 80%) but less than 60% to the VH sequences of other species in FR3. PMID- 7870055 TI - Covalently-bound human C4b dimers consisting of C4B isotype show higher hemolytic activity than those of C4A in the C3-bypass complement pathway. AB - The ability to form a covalent dimer of human C4b was investigated with purified isotypes C4A and C4B, and antibody-sensitized liposomes supplemented with C1. In this system, no C4A or C4B formed a complex with the antibody or C1. Whereas both C4A and C4B isotypes formed dimers to a similar extent, C4B formed an ester linked dimer and C4A an amide-linked dimer. Both of these dimers served as a subunit for the C3-bypass pathway C5 convertase, since liposomes bearing Ab, C1 and a dimer of C4A or C4B, allowed the formation of C5 convertase by the addition of C2. The degree of complement-mediated liposome lysis however, was observed to be 2-3 times higher in the C4B-bearing particles than in those bearing C4A. These results indicate that the second C4b-binding site on the first C4b is different between C4A and C4B, and that in the C3-bypass pathway, C4B has a higher degree of hemolytic activity than C4A, as in the conventional classical complement pathway. PMID- 7870056 TI - Immunoanalysis of human insulin using monoclonal antibodies reveals antigenicity of evolutionarily conserved residues. AB - Seven anti-human insulin monoclonal antibodies (mAb) were produced according to an efficient immunization protocol elaborated in our laboratory. Their affinity constants for the binding to the insulin molecule ranged from 5.0 x 10(8) M-1 to 1.0 x 10(10) M-1 when insulin was in solution and from 6.0 x 10(6) M-1 to 2.5 x 10(8) M-1 when insulin was adsorbed onto the microtiter plate. The antigenic sites on the insulin molecule recognized by these mAbs were mapped using two approaches. MAb pairs capable of binding simultaneously to human insulin in solution (using a two-site ELISA) or adsorbed onto a microtiter plate (using a competitive ELISA) were first sought. Three antigenic regions were defined on the surface of adsorbed human insulin and four on soluble insulin. Two distinct antigenic regions common to both the adsorbed and the soluble forms of insulin were defined by our mAbs. In a second approach, the immunological cross reactivities of these mAbs with species variants of insulin, chemically modified insulin of known structure and a panel of 78 overlapping nonapeptides covering the entire sequence of human proinsulin were assessed. Evidence was obtained that the epitopes recognized by the mAbs included residues conserved during evolution in the insulin molecule. The epitopic specificity of one group of mAbs (group I) was precisely defined. This group recognized a highly conserved region of the insulin molecule including residues 10-17 of the A chain. PMID- 7870057 TI - Intramolecular immunodominance and intermolecular selection of H2d-restricted peptides define the same immunodominant region of the measles virus fusion protein. AB - The generation of a sustained antibody response requires the participation of MHC class II-restricted T helper cells. We have identified class II-restricted sequences by immunizing BALB/c (H-2d) mice with 108 overlapping synthetic pentadecapeptides covering the whole sequence of the measles virus fusion protein (MV-F). Several strong T cell epitopes were found including a major cluster of H 2d-restricted peptides between amino acids 256 and 305. Some of these peptides including peptide F(421-435) and F(256-270) induced MV-specific T lymphocytes in vivo while other H2d-restricted MV-F sequences did not. Immunization with mixtures of selected peptides indicated a hierarchy among H2d-restricted sequences due to competition between peptides. The dominant peptide F(421-435) impaired the response to other T cell epitopes including F(256-270). The response to F(91-105) was obliterated by F(421-435) and F(256-270) but not by peptides devoid of a T cell epitope. When BALB/c mice were immunized with the MV, the immunodominant sequence F(421-445) was identified which included the synthetic peptide F(421-435). Our data suggest that competition during processing and/or presentation between H2d-restricted peptides defines the immunodominant sequence of the viral protein. Even though only a single immunodominant region was defined after immunization with the MV, peptides from other regions were able to induce MV-specific T cell responses. This finding is of interest for the design of subunit vaccines in general and for studying MV-specific T helper cells in an animal model in particular. PMID- 7870058 TI - Molecular characterization of a human V lambda VIII germline gene. AB - Human lambda light chains of the recently recognized variable region (VL) subgroup V lambda VIII can be distinguished from proteins of other V lambda gene families on the basis of distinctive chemical and serologic properties and by their preferential association with certain types of autoantibodies, i.e. rheumatoid factors (RFs). We now report that we have cloned from a human placental library a V lambda VIII-encoding germline gene, designated IGLV8A1, using as a molecular probe a partial V lambda VIII fragment generated by polymerase chain reaction (PCR) from genomic DNA. IGLV8A1 contained all the requisite elements of a potentially functional gene, including a V lambda exon with an open reading frame encoding 103 residues. Its expressed products were identified through analyses of cDNA cloned from two different monoclonal lambda VIII B-cell populations. The primary structure of lambda VIII light chains differed from that of lambda I, lambda II, lambda III, lambda IV and lambda VI proteins by the presence of distinctive residues within the first framework region (FR1) and an 11- rather than 7-residue second complementarity-determining region (CDR2). Remarkably, the IGLV8A1 gene was more homologous to the two functional rabbit V lambda germline genes, RV lambda 2 and RV lambda 3 (including the presence of one extra codon within the leader sequence), and to the murine V lambda x gene. Light chains encoded by the human, rabbit and mouse lambda VIII related genes shared certain unique primary structural features, notably the four additional CDR2 residues. The evolutionary conserved nature of the human V lambda gene and, in particular, the apparently novel tertiary structural effects induced by an elongated CDR2 provide evidence for the biological and functional importance of the V lambda VIII subgroup. PMID- 7870059 TI - Variable region light chain genes encoding human antibodies to HIV-1. AB - In previous work, it was found that the heavy chain variable gene (VH) repertoire of human antibodies to HIV is markedly skewed and that the gp120 molecule is a ligand for VH3 gene products. Here, we have analysed the light chain (L-chain) variable region genes (VL) expressed by a panel of human monoclonal antibodies derived from an immunized volunteer, an AIDS patient and seropositive asymptomatic donors, and specific for HIV-1 p25, gp41 and gp120 proteins. We found that, in contrast to VH gene-family use, the VL repertoire does not exhibit a family-bias. We noticed however, a tendency to the use of VL genes that map to the downstream portion of the kappa locus. The VL genes expressed have mutated at lower rates than the corresponding VH genes and show no clustering of the replacement mutations in the hypervariable regions. We also found that the third hypervariable regions (CDR3) of the L-chains have undergone a marked diversification, with addition of untemplated nucleotides, frequent truncation at the 3' end of the VLs and somatic mutation. These molecular events result in a length heterogeneity of the CDR3s and an apparently positive selection of specific highly reactive amino acids. We conclude that the specificity of, at least some of the anti-HIV antibodies, is dictated by the L-chain CDR3 regions which bear the imprints of antigenic selection. PMID- 7870060 TI - Cloning and characterization of murine CD6. AB - The lymphocyte antigen CD6 has been extensively studied in humans, but has not been reported in mouse. Here we describe the isolation and characterization of a cDNA clone encoding the murine homologue of the human lymphocyte antigen CD6. Comparison of the predicted amino acid sequence of human and murine CD6 shows that the cytoplasmic domain of murine CD6 is 160 residues longer than that of the human protein. Inspection of the 3' untranslated sequence of the human CD6 clone and the genomic organization of the murine CD6 gene suggests the expression of differentially spliced CD6 polypeptides in both species. PMID- 7870061 TI - Chimeric interleukin 2 receptor alpha chain antibody derivatives with fused mu and gamma chains permit improved recruitment of effector functions. AB - In order to investigate the feasibility of shuffling effector functions of monoclonal antibodies, we constructed chimeric antibodies with fused heavy chains. The derivatives studied are based on a monoclonal antibody directed against the alpha chain of the human Il2-R. Derivatives studied were the IgG1 and IgM isotypes; IgM delta, lacking the ability of multimerization due to a deletion; IgMc gamma 1 and IgGlc mu, with fused mu and gamma 1 chains and vice versa. IgG1, IgM delta and IgMc gamma 1 were secreted as monomers, IgM and IgG1c mu as polymers. The Ki values for competition with radio-iodinated Il2 with respect to binding to the Il2-R were markedly lower for polymeric than for monomeric derivatives (300-400 pM versus 2500-6500 pM). Recruitment of complement mediated by the deposition of C3 fragments, either of heterologous (rabbit) or homologous (human) origin, was mediated only by the polymeric derivatives IgM and IgG1c mu. ADCC was mediated by monomeric IgG1 and polymeric IgG1c mu, the latter derivative being active at concentrations 100-fold lower than the former. Together, the results demonstrate that both CDC and ADCC effector functions can be combined on a polymeric antibody derivative with fused gamma 1 and mu chains. In addition, such a derivative, due to its polymeric nature, has a high binding affinity. These properties may be important for the elimination of target cells in vivo. PMID- 7870062 TI - Polymorphism of the V alpha 15 T-cell receptor subfamily. PMID- 7870063 TI - Electron spin resonance study of the metal binding site of glucose specific peripheral blood lymphocyte lectin. AB - The electron spin resonance (ESR) spectrum of Mn2+ is highly responsive to changes in coordination symmetry. We have thus used ESR spectroscopy to study Mn2+ bound to goat peripheral blood lymphocyte lectin to delineate the nature of the metal binding site of the lectin. Our results suggest the presence of two metal binding sites on goat peripheral blood lymphocyte lectin, one a dissociable site which could bind Cu2+, Ca2+, Mg2+ and Ni2+ to displace bound Mn2+ and the other a non-dissociable site from which bound Mn2+ could not be displaced. Since no spectral changes are observed when D-glucose is bound, it is unlikely that Mn2+ participates directly in saccharide binding. PMID- 7870065 TI - Evidence for an early heavy chain intermediate in the assembly of H-2Db class I MHC molecules. AB - Several recently proposed models for the in vivo biogenesis of class I MHC molecules focus on the retention of empty dimers as a postulated intermediate in the assembly of the complete complexes. The data presented in this study support a slightly different model of class I biogenesis, which includes a precursor population of H-2Db heavy chains (HCs) that is retained in the ER of murine cells prior to its association with beta-2 microglobulin (beta 2m). For this study the intracellular ratios of the subunits that comprise class I molecules have been manipulated to generate a transfected cell line which assembles only very small numbers of unstable H-2Db molecules. Immunoprecipitation experiments with this transfected cell line demonstrated that nascent beta 2m was assembled into complete H-2Db heterotrimers more rapidly than nascent H-2Db HCs by normal murine cells. These data were not consistent with the simultaneous retention of the two associated subunits (HC and beta 2m) in a pool of precursor molecules. However, a previously uncharacterized subset of immature H-2Db HCs, which were not associated with beta 2m, has been detected. These immature HCs exhibited several characteristics of a precursor to complete class I molecules and required a supply of endogenously synthesized peptides for their normal processing in vivo. PMID- 7870064 TI - An early post-mutational selection event directs expansion of autoreactive B cells in murine lupus. AB - We report evidence for a strong selection event directing the outgrowth of autoreactive B cells in spontaneous murine lupus. The event occurred shortly following the induction of the somatic hypermutation process. This conclusion is derived from extensive sequence analyses of VH and VL loci expressed by hybridomas representing two large histone-specific clones (lineages) from an autoimmune (NZB x SWR)F1 mouse. To obtain unambiguous somatic mutational information, we devised a strategy to amplify and sequence the JH and JK clusters that flank expressed V genes. Somatic mutations in V flanking sequences of the two autoreactive clones revealed that in one clone the pattern was relatively simple: the frequency of mutation was low, and only one somatic mutation was shared by all clone members. Members of the second large histone-specific clone contained many somatic mutations in combinations that indicated numerous rounds of selection. Importantly, however, as observed with the first clone, one observed somatic mutation was shared by all clone members. Since, for each clone, all members shared only one visible mutation over extensive sequence tracts, we conclude that the autoreactive clones were derived from single precursors that had just begun to mutate their V genes. The data indicate that a strong selection event had occurred shortly after the initial acquisition of somatic mutation(s) in precursors to each clone, at a stage of development corresponding to that of the germinal center B cell approximately 1 week post immunization. PMID- 7870066 TI - VH shuffling can be used to convert an Fv fragment of anti-hen egg lysozyme specificity to one that recognizes a T cell receptor V alpha. AB - This study describes the isolation and characterization of Fv fragments that recognize a T cell receptor V alpha (V alpha 1934.4). A VH gene repertoire from an immunized mouse was recombined with the anti-hen egg lysozyme (HEL) V kappa D1.3 gene as single chain (sc)Fvs, and an Fv with reasonable affinity for binding to V alpha 1934.4 isolated. The Fv (VH14/V kappa D1.3) does not bind to HEL, indicating that the heavy chain shuffling has converted an anti-HEL specificity to one that recognizes the unrelated V alpha 1934.4. The association constant for the Fv-V alpha 1934.4 interaction has been determined using surface plasmon resonance (SPR) and is 1.2 x 10(7) M-1. Recombinant antibodies of reasonable affinity can therefore be generated by combining a VH library with a 'fixed' V kappa. To improve the affinity further, light chain shuffling has been used to generate an Fv (VH14/V kappa 9) that has a 30-fold higher affinity for binding to V alpha 1934.4 than the parent (VH14/V kappa D1.3) Fv, and SPR measurements demonstrate that the affinity improvement is due to an increase in on-rate. Unexpectedly, V kappa 9 differs from V kappa D1.3 by only two amino acids at positions 30 and 91 and, consistent with the change in binding affinity, both of these residues are located in CDRs. PMID- 7870067 TI - Cyclosporin-sensitive expression of cytokine mRNA in mouse macrophages responding to bacteria. AB - Characteristics of the cytokine response in resident mouse macrophages to certain Gram-positive and Gram-negative bacteria have been investigated by monitoring the expression of mRNA encoding interleukin-1 alpha and -beta (IL-1 alpha/beta) and tumor necrosis factor-alpha (TNF-alpha). Expression of these cytokine mRNAs occurred within 30-60 min. Both the flavonoid quercetin and phloretin inhibited the expression of IL-1 alpha/beta as well as TNF-alpha mRNA, with quercetin being more potent than phloretin and TNF-alpha expression somewhat more sensitive than that of IL-1 alpha/beta. Expression of all three cytokine mRNAs was also inhibited by prostaglandin E2, with an IC50 of > 1 microM, but not by the phosphodiesterase inhibitor pentoxifylline, although lipopolysaccharide-induced expression of TNF-alpha mRNA was inhibited. Down-regulation of phorbol ester sensitive isoforms of protein kinase C had virtually no effect on the cytokine response to bacteria, and treatment of resting macrophages with phorbol ester did not cause expression of any of the cytokine mRNAs investigated. Among protein phosphatase inhibitors, cyclosporin A caused extensive inhibition of bacteria induced expression of both IL-1 alpha/beta and TNF-alpha mRNA, while okadaic acid in itself caused selective induction of TNF-alpha, but not IL-1 alpha/beta mRNA, with a sharp peak at 0.3 microM concentration. At higher concentrations of okadaic acid, at which protein/phosphatase 2B/calcineurin would also be inhibited, the induction was completely reversed. This suggests that critical phosphorylation events, counteracted by one or more okadaic acid-sensitive protein phosphatase(s), and a dephosphorylation event carried out by a cyclosporin-sensitive protein phosphatase are both necessary for transcriptional activation of the TNF-alpha gene. PMID- 7870068 TI - Identification of active cytomegalovirus infection by analysis of immediate early, early and late transcripts in peripheral blood cells of immunodeficient patients. AB - Owing to the persistence of viral DNA in leukocytes after primary CMV infection, detection of CMV DNA in these cells does not necessarily represent active infection. To identify CMV replication more precisely we have analysed immediate early, early and late CMV transcripts by RNA amplification. The assay seems to be specific for active infection since no RNA-derived PCR products were obtained from healthy seropositive persons. The late UL83 transcript was detected in 80% of the patients with active CMV infections. Diagnosis of CMV replication by amplification of early and immediate-early transcripts was considerably less sensitive. In the case of continual CMV DNA detection in blood leukocytes by PCR without pp65 antigenemia the analysis of defined CMV transcripts would allow differentiation of active and non-active infection. In two cases the RNA assay became negative prior to DNA PCR analysis and pp65 antigen detection upon antiviral treatment, indicating that RNA amplification could be a suitable assay for early detection of the end of viral replication. No strong correlation was found between RNA detection and appearance of clinical symptoms. The development of CMV disease probably depends more on the extent of the functional impairment of the immune system. PMID- 7870069 TI - Rapid diagnosis of cytomegalovirus lung infection by DNA amplification in bronchoalveolar lavages. AB - We used polymerase chain reaction (PCR) to detect cytomegalovirus (CMV) deoxyribonucleic acid (DNA) in the bronchoalveolar lavages (BAL) of 16 CMV infected patients with active disease. We also tested PCR on a control group of 20 patients including latently infected patients without evidence of active CMV infection. Results were compared with those of CMV culture and of a rapid method of diagnosis which detects CMV in BAL cells by nucleic acid hybridization. PCR allowed the diagnosis in 93% of the actively infected patients compared to 73% for the CMV culture. Among the 20 control patients without evidence of active CMV infection, PCR was negative in all the 24 BAL tested. Hybridization on BAL cells with the CMV probe detected nine out of 10 actively infected patients, but the specificity of the test was only 68.5%. In our experience, PCR appears to be at least as sensitive as CMV culture, it provides results faster and it performs better than the detection of the virus by hybridization on BAL cells. Only active CMV infection was detected with the PCR conditions used in our study. This suggests that the PCR can be applied to bronchoalveolar lavage fluids as a rapid method to detect CMV lung infection. PMID- 7870070 TI - Detection of shigellae, enteroinvasive and enterotoxigenic Escherichia coli using the polymerase chain reaction (PCR) in patients returning from tropical countries. AB - We have used the polymerase chain reaction (PCR) to detect shigellae, EIEC and ETEC in stool specimens of diarrhoeic patients returning from tropical countries. As compared to culture (7.1% positive specimens), which recognizes only Shigella strains, PCR performed on bacterial growth from directly inoculated MacConkey agar plates and directed against virulence-associated genes present in both Shigella and EIEC was positive in 19.8% of the samples. We assumed that these additional positive results represent true rather than false positive samples because identical results for each single specimen were obtained using two different PCR systems and because positive results (culture as well as PCR) were exclusively found in patients with recent travel but not in those who acquired diarrhoea in a developed country where these organisms are not endemic. PCR detecting LT- and ST-specific sequences was positive in 18.5% of the patients with recent travel. Again no positive cases were identified in controls. Combining PCR and culture results, at least one bacterial pathogen was found in more than 50% of the patients with recent travel. We conclude that PCR is superior to culture methods for the detection of Shigella, EIEC and ETEC in travel-associated diarrhoea. PMID- 7870072 TI - Mycoplasma gallisepticum strain differentiation by arbitrary primer PCR (RAPD) fingerprinting. AB - We demonstrate here that the arbitrary primer polymerase-chain-reaction-based DNA fingerprinting method (also termed random amplified polymorphic DNA or RAPD) can be used to distinguish among strains of the avian pathogen Mycoplasma gallisepticum. Ten base oligonucleotide primers were used individually to prime DNA synthesis from genomic DNAs. Strain-specific arrays of DNA fragments were generated, which allowed us to identify and group isolates. Isolates of M. synoviae, M. gallinarum and M. iners yielded arrays of DNA fragments that differed markedly from those generated from the M. gallisepticum isolates using the same arbitrary primers. These results show that the RAPD fingerprinting method distinguishes genetically different strains of M. gallisepticum and indicates that it should be valuable for monitoring transmission of this pathogen. PMID- 7870071 TI - fimA and tctC based DNA diagnostics for Salmonella. AB - Immunochemical analyses of 85 isolates of 17 Salmonella serovars using polyclonal antiserum to SEF21, the type 1 fimbriae of Salmonella enteritidis, demonstrated antigenic relatedness among both type 1 and type 2 fimbriae of Salmonella. However, anti-SEF21 antiserum was not entirely suitable as a Salmonella diagnostic probe due either to a variability of, or a rare deficiency of, detectable fimbriae. Partial amino acid sequence analyses of the SEF21 structural fimbrin protein revealed 99% homology to Salmonella typhimurium FimA. Therefore, oligonucleotide probes for Salmonella detection were designed following sequencing of S. enteritidis fimA and comparison to the corresponding genes of S. typhimurium, Escherichia coli, Klebsiella pneumoniae and Serratia marcescens. One oligonucleotide probe hybridized to all 612 Salmonella isolates of 89 serovars tested while two other probes detected 97.5% and 99.7% of the isolates. Three consistently weak positive reactions were obtained, therefore, inclusivity was optimized by identification of a Salmonella-specific tctC DNA probe that detected 609 of 612 Salmonella isolates. No hybridization of these Salmonella probes was detected to 250 other Enterobacteriaceae isolates or to 14 other eubacterial species. Therefore, in combination, DNA probes to fimA and tctC proved to be highly reliable diagnostics for Salmonella bacteria. Accordingly, PCR assays targeting fimA and tctC were developed. PMID- 7870073 TI - Design and evaluation of new, highly sensitive and specific primers for polymerase chain reaction detection of HIV-1 infected primary lymphocytes. AB - Primer pairs in the HIV-1 POL and ENV genes were evaluated by performing a PCR on lysed peripheral blood mononuclear cells (PBMCs) from 96 HIV-1 seropositive and 40 seronegative individuals originating from 16 different geographical localities in Africa, Europe and Haiti. A single PCR using primer pairs to the LTR, GAG and ENV regions and detection by radioactively labelled oligonucleotide probes was compared to a nested PCR scheme using newly designed POL and ENV primers which used ethidium-bromide staining of the amplified product on agarose gel. The newly designed POL nested primer pair was shown to be highly sensitive (93%) and specific (100%) for the detection of HIV-1 proviral DNA of very diverse geographical and genetic origin, including highly aberrant HIV-1 isolates. The sensitivity of the newly designed ENV primers was 68.7%, which does not differ significantly from the sensitivity of the classical primers, SK 68/69. Both ENV primers were unable to amplify two SIVcpz isolates from naturally infected chimpanzees. PMID- 7870074 TI - Frequencies of the most common mutations responsible for phenylketonuria in Poland. AB - We screened 91 Polish phenylketonuric (PKU) children for the presence of 18 common mutations in the phenylalanine hydroxylase (PAH) gene, and 75.7% of PAH alleles were identified. The R408W mutation accounted for 54.9% of PAH mutant alleles. In the other 20.8%, eight mutations were detected: R158Q (6.6%), IVS10 (4.9%), IVS12 (2.7%), R261Q (2.2%), G272ter (1.65%), Y414C (1.1%), R252W (1.1%) and P281L (0.54%). Correlations between genotype and clinical phenotype were described. PMID- 7870075 TI - A novel mutation in the fibrillin gene (FBN1) in familial arachnodactyly. AB - Mutations of the fibrillin gene (FBN1) are known to cause classical Marfan's syndrome, ectopia lentis and neonatal Marfan's syndrome. We have identified a novel missense mutation in exon 28 of the FBN1 gene (R1170H) which is responsible for an atypical marfanoid phenotype characterised by dolichostenomelia and arachnodactyly. PMID- 7870076 TI - Identification of a novel exon 4 SOD1 mutation in a sporadic amyotrophic lateral sclerosis patient. AB - We have been screening a cohort of 46 sporadic and 10 familial amyotrophic lateral sclerosis patients for mutations in the superoxide dismutase gene (SOD1) using a combination of SSCP and direct PCR sequencing. A novel missense mutation (Asp101Asn) has been detected in one sporadic patient and a previously reported mutation has been found in two familial cases. PMID- 7870077 TI - Three new polymorphisms of the ApoAI-CIII-AIV gene cluster. PMID- 7870079 TI - 3rd International Congress of Movement Disorders. Orlando, Florida, November 7 11, 1994. Abstracts. PMID- 7870078 TI - Haplotype frequencies of three polymorphisms at the TIMP locus. PMID- 7870080 TI - In memoriam Charlotte Auerbach, FRS (1899-1994). PMID- 7870081 TI - Inhalation of benzene leads to an increase in the mutant frequencies of a lacI transgene in lung and spleen tissues of mice. AB - The goal of this study was to determine if inhalation of benzene leads to an increase in the mutant frequencies in the tissues of male C57BL/6 mice. Mutant frequencies were measured using a previously described assay in which bacteriophage lambda lacI transgenes are rescued from mouse genomic DNA as infectious phage and scored for their LacI phenotype. Eight experimental mice were exposed to a target concentration of 300 ppm of benzene for 6 h/day x 5 days/week x 12 weeks, and eight control mice were treated similarly except that they were not exposed to benzene. Mutant frequencies were calculated as the ratio of LacI-/total phage recovered from organs of interest. The mean mutant frequency measured in lung tissues of mice exposed to benzene was (10.6 +/- 1.4) x 10(-5), which is about 1.7-fold higher than that of the unexposed controls. In spleen tissues from benzene-exposed mice the mean mutation frequency was (12.6 +/- 4.1) x 10(-5), which is about 1.5-fold higher than that of spleen tissues from unexposed controls. The differences in mean mutant frequencies between benzene exposed and unexposed lung and spleen tissues are statistically significant. In liver tissues, however, the mean mutant frequencies of benzene-exposed mice and unexposed mice are not significantly different. These results demonstrate that inhaled benzene results in a statistically significant increase in the mutant frequencies in lung and spleen, but not in liver tissues of mice. PMID- 7870082 TI - Mutation spectra in Salmonella of sunlight, white fluorescent light, and light from tanning salon beds: induction of tandem mutations and role of DNA repair. AB - We evaluated the mutagenicity of sunlight (SUN), uncovered coolwhite fluorescent light (FLR), and light from a tanning salon bed (TAN) at the base-substitution allele hisG46 of Salmonella in four DNA repair backgrounds (wild type, uvrB, pKM101, and uvrB + pKM101). Approximately 80% of the radiation emitted by TAN was within the ultraviolet (UV) range, whereas only approximately 10% of the SUN and approximately 1% of the FLR radiation was UV. TAN emitted similar amounts of UVA and UVB, whereas SUN emitted 50-60x and FLR emitted 5-10x more UVA relative to UVB. Based on total dose (UV + visible), the mutagenic potency ranking was TAN > FLR > SUN. Using colony probe hybridization and PCR/DNA sequence analysis, approximately 3000 revertants were analyzed to determine the mutational specificity of the three light sources. The mutation spectra and those induced by 254-nm UV had common features. The uvrB mutation enhanced the mutagenicity of the environmental UV sources more (20-216x) than did the pKM101 plasmid (approximately 20x) relative to wild type DNA repair. All light sources induced equal proportions of transitions and transversions in excision repair-proficient strains, but they induced more transitions relative to transversions in uvrB containing strains. The majority of the mutations were G.C-->A.T transitions that were induced equally frequently at the first or second position of the CCC codon of the hisG46 allele in all strains except TA1535 (uvrB), where SUN and FLR induced transitions preferentially at the first position, and TAN induced them preferentially at the second position. Identified or presumptive multiple mutations, which constituted the only mutational class enhanced by all three light sources in the presence of uvrB and pKM101 either alone or together, accounted for 3-5% of the induced mutations in the plasmid-containing strains, and their increases (38-82-fold) in TA100 (uvrB, pKM101) were the highest of any mutational class. Of the TAN-induced multiple mutations, 83% (19/23) were CC-->TT tandem transitions. These results show that exposures to the nonsolar environmental UV sources FLR and TAN produce mutations similar to those produced by SUN, a known carcinogen. PMID- 7870083 TI - Absence of Ki-ras mutations in exocrine pancreatic tumors from male rats chronically exposed to gabapentin. AB - Human pancreatic malignancies originating from duct cells most frequently demonstrate activation of Ki-ras gene by G-to-A transition at codons 12 and 13. Rat pancreatic exocrine tumors more frequently and almost exclusively derive from acinar cells and thus differ morphologically from human pancreatic neoplasms. Male Wistar rats fed with 2% gabapentin (1-(aminomethyl)cyclohexane acetic acid) in diet for 2 years developed pancreatic exocrine adenomas and adenocarcinomas. To study the mutations in Ki-ras gene, rat pancreatic proliferative lesions induced by gabapentin were retrospectively analyzed by PCR amplification of DNA isolated from paraffin sections of formalin-fixed rat pancreatic adenomas and adenocarcinomas, using specific primers for regions encoding exon 1 (codon 12/13) and exon 2 (codon 61). The amplified 110-bp fragments of exon 1 and exon 2 were analyzed for mutations at codon 12/13 and 61. The results showed Ki-ras mutations at codon 12 in human pancreatic carcinomas. Novel mutations GGT-to-TGT and GGT-to CGT were detected at codon 12 in 1/5 and 2/5 human pancreatic tumors. Rat adenomas or carcinomas induced by gabapentin expressed wild type sequences at codons 12, 13 and 61. These findings were confirmed by allele-specific oligonucleotide hybridization, single-strand confirmation polymorphism of exon 1 and direct sequencing of exon 1 and exon 2. The absence of mutations in these rat pancreatic tumors suggests that these tumors do not correspond to the human tumors, and that the pathogenesis of this rodent tumor formation may follow different molecular mechanisms. PMID- 7870084 TI - Chromosome damage induced by combined treatments with restriction endonucleases introduced into CHO cells by single or double electroporation. AB - The possible recombination between non-homologous termini produced by restriction enzymes (REs) introduced in CHO cells by electroporation was studied. For this purpose, different combinations of REs that produced blunt or 5' overhanging DNA double-strand breaks were electroporated into cells either at the same time or separately by double electroporation experiments. Prior to double electroporation, it was confirmed that, once the cells have been electroporated, they resist a second electroporation, as assessed by cell viability analysis. Besides, the efficient and homogeneous introduction of labelled, non-permeable molecules was assessed by fluorescence microscopy. Our results showed interaction for most of the conditions, mainly when the REs were introduced separately. Differences found in the degree of interaction between the combinations studied are discussed. PMID- 7870085 TI - Sister-chromatid exchanges after exposure to metal-containing emissions. AB - The effect of in vivo feeding of metal-containing emissions from an aluminum refining plant upon the induction of sister-chromatid exchanges (SCEs) and mitotic delay was investigated in cultured sheep lymphocytes. The experimental animals were given a daily dose of industrial emissions (mostly aluminum and fluoride) of either 0.75 g or 1.5 g/animal, for 1 year. The experiments were aimed at induction of chronic fluorosis under clinical conditions. A significant increase in mean serum fluoride, aluminum, arsenic and cadmium levels between both experimental groups and control was observed from 5 and 7 months on, respectively. The occurrence of SCEs in the experimental groups was higher (reaching statistical significance at a dose of 1.5 g/animal) than that seen in the controls. The emission was found to reduce the proliferation index. A significant heterogeneity of the first, second and third metaphases as compared to the controls was also observed. PMID- 7870086 TI - Effect of glutathione on sister-chromatid exchanges in normal and buthionine sulfoximine-treated mice. AB - Based on their ability to induce sister-chromatid exchanges (SCEs) it is evident that thiol-containing radioprotectors can induce DNA damage. However, there were contradictory findings when reduced glutathione (GSH) was tested using two cell lines. The present study demonstrated that GSH can induce SCEs and also delay in cell proliferation in mouse bone marrow cells in vivo. The presence of catalase significantly reduced GSH-induced SCE frequency down to catalase alone levels. An attempt was made to evaluate the effect of GSH treatment in buthionine sulfoximine (BSO)-treated mice (GSH-depleted mice) and the data indicate that induction of SCEs takes place without inducing a delay in cell proliferation or the generation of hydrogen peroxide. Probably, some unknown route is involved by which GSH-degraded product(s) induce SCEs in BSO-treated mice. Therefore, the induction of SCEs by GSH in normal mice may be largely due to hydrogen peroxide generation; however, the involvement of the binding ability of GSH to chromatin and the probable (unknown) route by which GSH-degraded product(s) may cause smaller fraction of SCEs cannot be ruled out. PMID- 7870088 TI - Transgenic lambda/lacI mutagenicity assay: statistical determination of sample size. AB - Statistical analysis of the lambda/lacI transgenic mutagenicity assay was used to determine optimal sample size and resource allocation in terms of number of animals and number of recovered target genes (recovered phage) required to demonstrate a statistically significant induction in mutant frequency. Statistical assumptions as applied to mutagenicity data are discussed for a number of frequently used statistical analyses. Log transformations are suggested as a means of meeting statistical assumptions and examples are given on interpreting results of analyses of log transformed data. The data analyzed in this study indicate that 300,000 lambda plaques from each of five animals should be analyzed per treatment group in order to detect a doubling of mutant frequencies. Additional sensitivity is gained primarily through increase of animal number and not the number of phage rescued, due to inherent animal-to animal variability. PMID- 7870087 TI - International Commission for Protection against Environmental Mutagens and Carcinogens. An evaluation of the genetic toxicity of paracetamol. AB - During the last years, several reports have indicated genotoxic effects of paracetamol, a widely used non-prescription analgesic and antipyretic drug. Thus, a careful evaluation of a possible genotoxic effect related to paracetamol use is warranted. Studies in vitro and in vivo indicate that the reactive metabolite of paracetamol can bind irreversibly to DNA and cause DNA strand breaks. Paracetamol inhibits both replicative DNA synthesis and DNA repair synthesis in vitro and in experimental animals. Paracetamol does not cause gene mutations, either in bacteria or in mammalian cells. On the other hand, a co-mutagenic effect of paracetamol has been reported. Furthermore, paracetamol increases the frequency of chromosomal damage in mammalian cell lines, isolated human lymphocytes and experimental animals. Two independent studies have shown an increase in chromosomal damage in lymphocytes of human volunteers after intake of therapeutic doses of paracetamol, whereas a third study was negative. Paracetamol-induced chromosomal damage appears to be caused by an inhibition of ribonucleotide reductase. This indicates that a threshold level for the paracetamol-induced chromosomal damage may exist. Genotoxic effects of paracetamol have, however, been demonstrated both in vitro and in vivo at or near therapeutic concentrations. The data indicate that the use of paracetamol may contribute to an increase in the total burden of genotoxic damage in man. Thus, there may be a need to evaluate the therapeutic benefit of paracetamol, taking into consideration not only its potential to induce acute and chronic organ damage, but also genotoxic effects. PMID- 7870089 TI - Active dissociation of Hoechst 33342 from DNA in living mammalian cells. AB - The fluorescent dye Hoechst 33342, which binds tightly to DNA in the minor groove, can be effectively extracted from the DNA in vivo due to an energy dependent process. It is the dissociation of the dye from DNA rather than its removal from a cell that has a critical role in this process. The dissociation can be suppressed by the topoisomerase-2 inhibitors novobiocin, ellipticine and etoposide. Breaks in the DNA also inhibit the process. The dissociation of the dye requires that DNA remain intact along a region of at least several thousand base pairs. It is proposed that DNA in mammalian cells is a dynamic, conformationally nonstable system and that topologically closed loops consisting of several thousand base pairs constantly appear and disappear in chromatin. PMID- 7870090 TI - Ni(II) induced changes in cell cycle duration and sister-chromatid exchanges in cultured human lymphocytes. AB - Investigations from our laboratory and others have shown that Ni(II) treatments of cultured human lymphocytes produced a relatively small but significant increase in SCE frequency. Based on the known effects of Ni(II) on DNA replication, we evaluated whether Ni(II) produced a cell cycle delay in lymphocytes. Human lymphocytes of three normal subjects were exposed to 5, 10, and 25 microM of NiSO4 in culture medium and scored for the percent of metaphases in the first (M1), second (M2), and third (M3) cell cycle for harvest times spaced every 4 h from 36 to 72 h after culture initiation. Cell cycle duration was studied using Tice's BISACK method with certain modifications. All three doses of NiSO4 caused a delay of nearly 1.5 h in the initiation of cell division, but only 25 microM NiSO4 caused a lengthening in the cell cycle time of nearly 4 h for completion of the first cycle. Only at the highest dose of Ni(II) was there a significant increase in the SCE frequency compared to the control. When the proliferation rate index (PRI) was examined, the effect of 5 or 10 microM Ni(II) was negligible while the 25 microM concentration caused a suppression in the proliferation rate. The effect of Ni(II) on the cell cycle was much more pronounced than on the PRI. A significant increase in SCE frequency was observed only for the concentration of Ni(II) that caused a pronounced cell cycle delay, a result that is consistent with prior studies showing higher SCE responses for chemical treatments that lengthen the cell cycle. PMID- 7870091 TI - Photoinduction of micronuclei by 4,4',6-trimethylangelicin and 8-methoxypsoralen in different experimental models. AB - The frequencies of micronuclei induced by treatment with 4,4',6 trimethylangelicin (TMA) and 8-methoxypsoralen (8-MOP) have been compared in the following experimental models: (1) peripheral normochromatic erythrocytes (NCE) during 10 days after single p.o. administration of TMA or 8-MOP in male and female mice; (2) peripheral NCE during photocarcinogenesis by TMA or 8-MOP topically administered to female mice; (3) primary cultures of human skin fibroblasts treated with TMA or 8-MOP. The frequency of micronuclei in peripheral NCE of mice (both sexes) was significantly enhanced after p.o. administration of TMA or 8-MOP. This latter was more active than TMA in inducing chromosomal damage. No increased frequencies of micronuclei in peripheral NCE were detected in mice subjected to TMA or 8-MOP photocarcinogenic treatment, even when malignancies developed. In human fibroblast cultures, at equimolar concentrations, the induction of lethal effects by TMA in the presence of 365-nm radiation was higher than that exerted by 8-MOP. At equal survival, however, TMA showed practically the same activity as 8-MOP in the induction of micronuclei. Our findings provide evidence of genotoxicity by TMA administered p.o. without irradiation and give further information about photogenotoxicity of these substances. PMID- 7870092 TI - Chromosomal aberrations induced in human whole blood cultures by pipetting cell pellets in the presence of AluI. AB - A physical method is described to permeabilize human peripheral lymphocytes in culture for the restriction endonuclease AluI. Blood cultures are incubated for 20 h, pelleted, strongly pipetted with different types of Pasteur pipettes in the presence of AluI and recovered for up to 54 h in the presence of 5 bromodeoxyuridine. Up to 20% of aberrant first posttreatment (M1) metaphases with chromosome-type aberrations are found. The method works with whole blood cultures and is therefore easy to perform. PMID- 7870093 TI - Induction of aneuploidy in Chinese hamster oocytes following in vivo treatments with trimethoxybenzoic compounds and their analogues. AB - Many inhibitors of tubulin polymerization have a trimethoxybenzene ring in their molecules. Such trimethoxybenzoic compounds and their analogues may therefore have a potency to induce meiotic nondisjunction of oocytes. In this study, a single dose of reserpine (0.5 microgram/g body weight), podophyllotoxin (20.0 micrograms/g b.w.), trimethoxybenzoic acid (500.0 micrograms/g b.w.) or vinblastine sulfate (3.0 micrograms/g b.w.) was injected intraperitoneally to mature female Chinese hamsters at the onset of the first meiotic spindle formation of oocytes. Within 6 h after spontaneous ovulation, MII oocytes were collected from the oviducts for morphological examination and cytogenetic analysis. The incidence of morphologically abnormal oocytes with unusually large first polar body or bodies increased significantly after the treatment with reserpine (18/202; 8.9%), podophyllotoxin (28/172; 16.3%) and vinblastine sulfate (63/197; 32.0%), as compared with the control (3/214; 1.4%). Chromosome analysis of oocytes revealed that podophyllotoxin and vinblastine sulfate were effective in inducing aneuploidy (62/154; 40.3% and 128/156; 82.1% vs. 3/198; 1.5% of the control) by inhibiting the formation of spindle microtubules at the first meiosis. Aneuploids were found more frequently in morphologically abnormal oocytes than in normal oocytes. No aneugenic activity of reserpine and trimethoxybenzoic acid was observed. These results indicate that trimethoxybenzoic compounds do not necessarily exhibit aneugenic activity. PMID- 7870094 TI - The need for three dose levels to detect genotoxic chemicals in in vivo rodent assays. PMID- 7870095 TI - Intercomparison in cytogenetic dosimetry among five laboratories from Latin America. AB - As part of a regional International Atomic Energy Agency (IAEA) collaborative project within Latin America, five countries participated in an intercomparison in cytogenetic dosimetry. Coded slides for chromosomal aberrations and micronucleus analyses were prepared by the coordinator laboratory which organized the exercise and sent to the other participating laboratories. For estimates of dose, each laboratory scored the frequency of dicentrics in metaphases and the frequency of micronuclei in binucleated cells. The lymphocytes were irradiated with 60Co gamma-rays (0, 0.75, 1.5 and 3.0 Gy). Eleven of the 15 estimates of dose based on dicentrics and nine of the 12 based on micronuclei fell within +/- 30% of the true dose. When considering the uncertainties of the dose estimates, the true dose fell within the 95% confidence limits of the estimates on eight of the 15 occasions for dicentrics and four of the 12 for micronuclei. PMID- 7870096 TI - Chromosomal aberrations and micronuclei in reinforced plastics workers exposed to styrene. AB - The aim of this study was to investigate the cytogenetic changes induced in humans exposed to styrene in a reinforced plastics plant. Blood and urine samples were collected from 18 styrene exposed workers and 18 age and sex matched control subjects from the administrative department of the same factory. Chromosome aberrations (CAs) and micronuclei (MN) (cytokinesis block method) were analyzed in blood lymphocytes. All of the subjects included in the study were male non smokers. The duration of employment ranged from 10 to 22 years (14.3 +/- 4.4). In order to monitor exposure to styrene, urinary mandelic acid (MA) levels were measured using a standard colorimetric method. The level of thioethers in the urine was also determined colorimetrically. The mean level of mandelic acid was significantly higher in the exposed workers (328.44 +/- 266.21 mg/g creatinine) compared with that of the controls (50.09 +/- 16.84 mg/g creatinine) (p < 0.05). The level of urinary thioethers was found to be higher among the exposed workers. The number of cells with chromosomal aberrations was significantly higher in the workers (6.06 +/- 4.41) compared with the controls (3.44 +/- 2.28) (p < 0.05). There was no significant increase in the frequency of micronuclei in the exposed workers compared to controls. Our results support earlier findings on increased rates of chromosomal aberrations in reinforced plastics workers. PMID- 7870097 TI - A sequential approach to testing with the rodent bone marrow micronucleus assay- obviation of the need for statistical analyses of data. AB - The 'sequential' protocol we use for the conduct of mouse bone marrow micronucleus assays is described. The most important criterion for activity in the assay is the reproducibility of any induced effects. The frequencies of micronucleated polychromatic erythrocytes among 239 male CBA control mice are displayed and discussed. Our decision to avoid statistical analysis when assessing mouse bone marrow micronucleus data is explained. PMID- 7870098 TI - Inter-strand cross-linking of Vibrio cholerae DNA induced by furazolidone: a quantitative assay by four simple methods. AB - Four simple methods, i.e., (i) UV absorption spectrophotometry, (ii) hydroxyapatite chromatography, (iii) fluorescence analysis of ethidium bromide bound to DNA and (iv) assay of S1 endonuclease action, were used in parallel for the estimation of furazolidone-induced inter-strand cross-links in Vibrio cholerae DNA. The data produced by the four methods were in reasonable agreement with each other and provided similar linear dose-response relations, the correlation (between dose and response) coefficient being in any case numerically greater than 0.98. When the data obtained by four independent methods were plotted in a single graph, the resulting dose-response relation could be described by the equation log NR = 1.41 - 0.54 log D, where NR is the % non reversible DNA remaining in the cells treated by furazolidone at dose D micrograms/ml x h. The correlation coefficient in this plot was -0.98 and significant to a level better than 0.1%. This study thus brings out that any one of these four methods can be used with reasonable confidence for the diagnosis and assay of inter-strand cross-links in DNA. PMID- 7870099 TI - Intralaboratory optimization and standardization of mutant screening conditions used for a lambda/lacI transgenic mouse mutagenesis assay (I). AB - A lambda/lacI shuttle vector transgenic mouse mutagenesis assay has been optimized and standardized for reproducible mutant detection. The mutagenic endpoints are blue lacI- phage plaques on a bacterial lawn resulting from the de repression of beta-galactosidase activity acting on the chromogenic substrate X gal. Non-mutant lacI phage plaques remain colorless. Factors demonstrated to affect mutant detection include X-gal concentration per assay tray, plaque density per assay tray, pH of plating agar, incubation time at 37 degrees C and the use of a red translucent screening filter over a light source to enhance mutant plaque visibility. In vivo mutant frequencies for liver in untreated animals using standard protocols and internal controls were repeatable in separate experiments using lambda/lacI B6C3F1 mice (4.3 +/- 1.2 x 10(-5) and 4.1 +/- 0.8 x 10(-5)). These studies analyze the use of internal controls to monitor the level of mutant phage plaque detection in a given experiment and evaluate the repeatability of observed mutant frequencies obtained when using standardized procedures. PMID- 7870100 TI - Interlaboratory comparison: liver spontaneous mutant frequency from lambda/lacI transgenic mice (Big Blue) (II). AB - Spontaneous mutant frequency in livers of two transgenic mouse strains, each carrying identical lambda shuttle vectors with a lacI target gene, was evaluated by two laboratories. These studies investigated variability in spontaneous mutant frequency between animals and as a function of the number of phage screened. Liver DNA was independently isolated from 7-11 week old C57BL/6 and B6C3F1 Big Blue transgenic mice. At least 500,000 phage were screened for mutation at lacI for each animal using standardized assay procedures. In the two labs, the C57BL/6 liver spontaneous mutant frequency was 45 +/- 9 x 10(-6) and 41 +/- 7 x 10(-6). The B6C3F1 liver spontaneous mutant frequency was 42 +/- 10 x 10(-6) at one lab and 43 +/- 12 x 10(-6) and 41 +/- 8 x 10(-6) in two trials at the second lab. Mean mutant frequency data from both labs, calculated in increments of 100,000 plaque forming units (pfu) scored for each mouse strain, show stabilized mean mutant frequency and standard deviation after approximately 200,000-300,000 pfu screened. The frequency of spontaneous lacI mutants was reproducible both within and between labs and was comparable between the two transgenic mouse strains. PMID- 7870101 TI - Mutagenicity and mutation spectra of 2-acetylaminofluorene at frameshift and base substitution alleles in four DNA repair backgrounds of Salmonella. AB - We used colony probe hybridization procedures to determine the mutations in approximately 600 revertants of the -1 frameshift allele hisD3052 and approximately 200 revertants of the base-substitution allele hisG46 of Salmonella typhimurium induced by 2-acetylaminofluorene (2-AAF) in the presence of Aroclor induced rat liver S9. 2-AAF was primarily a frameshift mutagen, exhibiting 5 times more frameshift than base-substitution activity. The only frameshift mutation 2-AAF induced at the hisD3052 allele was a hotspot (-2) deletion within the sequence CGCGCGCG. The addition of the pKM101 plasmid had a small effect on the mutagenic potency of 2-AAF at this allele in a uvr+ background and no effect on the mutation spectra in either a uvr+ or uvr- background. The small amount of base-substitution activity exhibited by 2-AAF at the hisG46 allele required the presence of both the pKM101 plasmid and the uvrB mutation. The base substitutions were G.C-->T.A transversions (86%) and G.C-->A.T transitions (14%), and 85% of the substitutions were at the second position of the CCC target of the hisG46 allele; the remainder were at the first position. We propose that the hotspot frameshift may be initiated by N-acetyl-2-aminofluorene adducts located at the C(8) position of any of the guanines except the first one in the CGCGCGCG hotspot sequence. The mutation might then result from correct incorporation of cytosine opposite the adducted guanine, followed by a 2-base slippage according to our recently proposed correct-incorporation/slippage model. The hotspot mutation may also result from a 2-AAF-induced B- to Z-DNA transition at the repeating GpC site as well as by the action of enzymes involved in DNA metabolism, such as DNA resolvases or topoisomerases, on DNA structures that have been distorted by 2-AAF adducts. The small amount of 2-AAF-induced base-substitution activity may be due to mispairing of adenine opposite the minor aminofluorene adduct at the C(8) position of guanine. PMID- 7870102 TI - Triethylenemelamine: induction of specific-locus mutations in the ad-3 region of heterokaryon 12 of Neurospora crassa. AB - The mutagenicity of the trifunctional alkylating (or cross-linking) agent TEM (triethylenemelamine or 2,4,6-tris(1-aziridinyl)-1,3,5-triazine) in the adenine-3 (ad-3) region was studied with a two-component heterokaryon (H-12) of Neurospora crassa. The objective was to characterize the genetic damage produced by this chemical to determine the spectrum of specific-locus mutations induced in a lower eukaryotic organism and to compare this spectrum with that induced in the mouse. Specific-locus mutations in the ad-3 region of strain H-12 result from gene/point mutations, multiple-locus mutations, and multilocus deletion mutations at the closely linked ad-3A and ad-3B loci. These loci control two sequential biochemical reactions in the purine biosynthetic pathway. A 0.1 M solution of TEM was used to treat conidial suspensions of H-12 for 20, 40, 80, 120, or 170 min to obtain dose-response curves for (1) inactivation of conidia, and (2) the induction of specific-locus mutations in the ad-3 region. These experiments demonstrated that TEM is a strong mutagen (maximum forward-mutation frequency between 100 and 1000 ad-3 mutations per 10(6) survivors) for the induction of specific-locus mutations in the ad-3 region. Both biochemical and classical genetic tests were used to characterize the TEM-induced ad-3 mutations from each of the five treatment groups to distinguish between the different genotypic classes and subclasses. The overall data base from these genetic studies demonstrates that TEM-induced ad-3 mutations result predominantly (95.5% [769/805]) from gene/point mutations at the ad-3A and ad-3B loci, and from a low percentage (4.5% [36/805) of multilocus deletion mutations. In addition, TEM induces an unusually high frequency of multiple-locus mutations with sites of recessive lethal damage closely linked with the ad-3 region. Comparison of the dose-response curves for the major classes and subclasses of TEM-induced ad-3 mutations demonstrates (1) that gene/point mutations and multilocus deletion mutations increase as the 1.4 power of TEM treatment time, and (2) that the two classes of TEM-induced multiple-locus ad-3 mutations consisting of gene/point mutations with separate sites of recessive lethal damage increase at about the 1.96 power of TEM treatment time. When the data from the present specific-locus studies are compared with those in the mouse, we find, insofar as such comparisons are possible, that a similar spectrum of specific-locus mutations has been induced by TEM in each assay system. PMID- 7870103 TI - Charcot-Marie-Tooth neuropathies: from clinical description to molecular genetics. AB - Ninety-five families with Charcot-Marie-Tooth (CMT) neuropathies were studied clinically, electrophysiologically (MNCVs and EMGs), and by molecular genetics. Fifty-four families (56.8%) were type 1A mapped at 17p11.2-p12 and DNA duplication was present in 50 (92.6% of CMT1A families). One family with type 1B (1.1%) mapped at 1q22-q23 showed a point mutation of the myelin P0 gene. Eighteen families (18.9%) were type CMT2 based on electrophysiological studies. Molecular genetics was not yet conclusive. Twenty CMT families were with X-linked dominant inheritance (CMTX1) (21.1%) mapped at Xq13.1 and connexin 32 (CX32) point mutations were present in 15 families (75%) (five nonsense mutations, eight missense mutations, two deletions). Two CMT families (2.1%) with X-linked recessive inheritance showed no point mutations of CX32 and their mapping was different from CMTX1, respectively at Xp22.2 for CMTX2 and at Xq26 for CMTX3. PMID- 7870104 TI - Early and late motor evoked potentials reflect preset agonist-antagonist organization in lower limb muscles. AB - A single transcranial magnetic stimulus can evoke two involuntary muscle responses in lower limb muscles of healthy humans. The purpose of the present study was to find out if these responses, when evoked during the processing period of a simple or choice reaction time task, such as ankle dorsiflexion, have specific characteristics related to the task. During the auditory reaction time, a transcranial magnetic stimulus was delivered to observe changes in the excitability of the central nervous system. A dual-cone coil was used, which effectively stimulated the fairly deep-lying lower limb motor cortex. Stimuli were delivered in a random order with 20-300-ms delays from the auditory go signal. Motor evoked potentials (MEP) in right and left anterior tibial and soleus muscles were analyzed while early MEPs were observed invariably in both muscles; late MEPs occurred consistently only in soleus muscles. Both early and late MEP amplitudes were larger in simple reaction time trials than in choice reaction time trials. The late MEP appeared earlier in the simple reaction time task than in the choice reaction time task, reflecting faster central processing of simple reaction time tasks. The amplitude of the soleus late MEP in the simple reaction time task followed closely the amplitude of anterior tibial early MEP, suggesting a preset agonist-antagonist organization. This relationship was not present in the choice reaction time task. PMID- 7870105 TI - Evaluation of the cardiomyopathy in Becker muscular dystrophy. AB - To evaluate the features and the course of cardiomyopathy in Becker muscular dystrophy, 68 patients--identified by clinical assessment and by reduced dystrophin labeling and/or DNA analysis--were followed in the years 1976-1993, for periods ranging from 3 to 18 years (mean 8). Patients periodically underwent clinical, electrocardiographic, echocardiographic, nuclear, and radiological assessments. Preclinical cardiac involvement was found in 67.4% of patients under 16 years of age, decreasing to 30% in patients older than 40. Clinically evident cardiomyopathy was found in 15% of patients under 16 years of age, increasing to 73% in patients older than 40. A real, dilated cardiomyopathy is the most frequent type of myocardial involvement after the age of 20. Results show that the severity of cardiac involvement can be unrelated to the severity of skeletal muscle damage and confirm that cardiac dysfunction is a primary feature of Becker muscular dystrophy. PMID- 7870106 TI - Motor unit recruitment pattern during low-level static and dynamic contractions. AB - Motor unit (MU) recruitment patterns were studied during dynamic and static contractions at workloads corresponding to 10% of maximal voluntary contraction force. The dynamic contraction consisted of a 20 degrees flexion and extension of the elbow performed with a velocity of 10 degrees/s. Motor unit potential trains were recorded from the brachial biceps muscle of 6 healthy females using a quadripolar needle electrode and a computerized decomposition program. Properties of the identified MUs were derived from concentric needle EMG. A total of 119 MUs were identified during dynamic contractions, 107 MUs during static anisotonic contractions, and 96 MUs during static isotonic contractions. The main result was that MUs recruited during different contractions showed similar properties and may belong to the same part of the motoneuron pool. This indicates that MU recruitment patterns during dynamic contractions may be almost as stereotypical as during static contractions and may even activate the same MUs. PMID- 7870107 TI - Primary sensory neurons in X-linked recessive bulbospinal neuropathy: histopathology and androgen receptor gene expression. AB - Pathology of the primary sensory neurons was examined in 7 autopsied patients and 6 biopsied sural nerves from the patients with X-linked recessive bulbospinal neuronopathy (SBMA). Large myelinated fibers in the central rami (L-4 posterior root, L-4, T-7, and C-6 segment of the fasciculus gracilis), and in the peripheral rami (sural nerve) were diminished in a distally accentuated manner, while small myelinated and unmyelinate fibers were well preserved in number. Demylinating process and axonal atrophy was ubiquitous. The diameter frequency histograms of the dorsal root ganglion (DRG) neurons showed a decrease in the number of large diameter neurons and an increase in the number of small diameter neurons without substantial loss of whole number of neurons, which suggested that neuronal size was atrophied. These data suggested central and peripheral distal axonopathy with neuronal atrophy was the process of sensory neuron involvement. Expression of mutant androgen receptor mRNA with elongated CAG repeat in the DRG and sural nerve supported the view that sensory nerve involvement is the primary process in SBMA. PMID- 7870108 TI - The all ulnar motor hand without forearm anastomosis. AB - Anomalous ulnar innervation of intrinsic hand muscles, inferred in a number of clinical series, has been documented only rarely in electrophysiological studies. Using near-nerve and standard conduction studies we evaluated 2 cases with nearly exclusive ulnar innervation of hand muscles. There was no evidence of anomalous communication in the forearm. Digital sensory fibers were normally distributed in median and ulnar nerves. The anomalous motor innervation most likely results from palmar communication between ulnar and median branches (Riche-Cannieu anastomoses). The normal distribution of digital afferents suggests that such anastomoses are formed primarily by motor axons. PMID- 7870109 TI - Motor neuron disease: a primary disorder of corticomotoneurons? AB - It has been suggested that the primary site of damage in motor neuron disease (MND) is the cortical motor neuron, with secondary degeneration of spinal motor neurons. To test this hypothesis, we sought to determine if loss of corticomotoneurons in MND precedes spinal motor neuron loss. The density of corticomotoneurons was measured in 18 MND and 9 control cases using 10-microns horizontal sections of motor cortex in the hand/arm region. The density of spinal motor neurons was measured in 10-microns transverse sections of the lower cervical spinal cord. Corticomotoneuron and spinal motor neuron densities were decreased in MND cases compared to controls, but in MND cases there was poor correlation (r2 = 0.06) between corticomotoneuron and spinal motor neuron densities. The results indicate that corticomotoneuron and spinal motor neurons are lost at different rates in different MND patients, and that corticomoteneuron loss is unlikely to be a primary event in MND. PMID- 7870110 TI - Direct spinal stimulation for intraoperative monitoring during scoliosis surgery. AB - Intraoperative electrophysiological monitoring of the spinal cord has traditionally been done by recording somatosensory evoked potentials (SEP). There is a risk that SEPs can be unaltered when significant injury to the anterior spinal cord has occurred. The purpose of this report is to describe a simple technique for intraoperative spinal cord stimulation which monitors descending pathways in the anterior spinal cord. Stimulation occurs through needle electrodes inserted into spinous processes in the rostral surgical wound, and recordings are made from electrodes in the popliteal spaces. We report our experience in monitoring spinal instrumentation in 45 patients with idiopathic scoliosis and 20 with some form of neurological disease causing scoliosis. The neurogenic motor evoked potentials (NMEP) are stable and easily recorded from the popliteal spaces in the majority of patients. We describe the case of 1 patient with Friedreich's ataxia in whom no SEPs could be recorded, but NMEPs were used successfully for monitoring. We have fond that combining traditional SEP monitoring with NMEP recording provides a safe and effective method to monitor the spinal cord during surgical procedures where it is at risk. PMID- 7870111 TI - An EMG case report of lead neuropathy 19 years after a shotgun injury. AB - The clinical picture of lead neuropathy was classically described as a painless progressive motor neuropathy with axonal loss. The literature review fails to demonstrate a consensus on the site of axonal loss. This is an EMG report of a patient who developed a late lead neuropathy after a shotgun injury. A 69-year old Filipino, healthy, male nondrinker sustained a shotgun injury to his left elbow. Nineteen years later he developed abdominal pain, followed by generalized weakness, distal greater than proximal in the extremities, and impaired pin prick, proprioception, and two-point discrimination. He became nonambulatory and totally dependent in daily activities. He was lost to follow-up for 2 years until January 1993 when he presented with a blood lead level of 84 micrograms/dL. EMG examination revealed a sensorimotor peripheral polyneuropathy with severe axonal loss. This case demonstrates that axonal loss is the predominant feature in lead neuropathy and the location of pathology is in the peripheral nerves. PMID- 7870112 TI - Phrenic nerve conduction study in normal subjects. AB - Phrenic nerve conduction studies were performed in 50 phrenic nerves from 25 normal subjects using a technique modified from previously described methods. The normal ranges for latency, amplitude, negative peak area, and duration were established. The latency correlates with age and the amplitude increases with chest circumference. With our method, the amplitude increases and the duration decreases with lung volume. We found good right-left agreement and reproducibility. Therefore, the unaffected side can be used as a reference in unilateral phrenic nerve lesions and previous studies can be used for comparison in serial studies. We recommend that phrenic nerve conduction studies be used routinely to diagnose and monitor patients with respiratory involvement from neuromuscular diseases. PMID- 7870113 TI - Comparison of the flexed and extended elbow positions in localizing ulnar neuropathy at the elbow. AB - Electrophysiologic localization of ulnar neuropathy at the elbow often depends on demonstration of segmental slowing. Based on normative data obtained from 50 control subjects, we compared the utility of flexed and extended elbow positions in demonstrating focal slowing at the elbow as compared to the forearm segment in patients with ulnar neuropathy. We studied 35 patients with ulnar neuropathy with definite electrophysiologic localization to the elbow segment defined by conduction block across the elbow segment or by focal slowing demonstrated either in the flexed or extended position. Applying cutoff values from the control group, all 35 patients demonstrated focal slowing at the elbow in the flexed position, whereas only 5 of 35 (14%) patients did so in the extended position. We conclude that the flexed elbow position is more sensitive than the extended position in localizing ulnar neuropathy at the elbow and should be the preferred method when performing ulnar motor conduction studies. PMID- 7870114 TI - Isolated femoral mononeuropathy to the vastus lateralis: EMG and MRI findings. AB - A 16-year-old female track athlete experienced sudden onset of right anterolateral thigh pain, initially thought to be cramping. After 2 months of continued postexercise pain she sought medical evaluation. A 3-cm thigh circumference discrepancy was noted on physical exam. She was referred for electromyography (EMG) and magnetic resonance imaging (MRI) studies. Femoral and screening nerve conduction studies were normal. Needle EMG revealed acute neuropathic changes confined to the right vastus lateralis only. These findings were confirmed by MRI, including short T1 inversion recovery (STIR) sequences. All other medical work-up was normal, including lumbar and pelvic MRI, and complete serologic studies. This case represents a unique presentation of an idiopathic femoral mononeuropathy isolated to the vastus lateralis only, which has not been previously reported. The highly unusual anatomical presentation of this case illustrates the emerging complementary usefulness of EMG and MRI in delineating neuromuscular pathology. PMID- 7870115 TI - The limitations of the dorsal ulnar cutaneous sensory response in patients with ulnar neuropathy at the elbow. PMID- 7870116 TI - A macro-EMG study in chronic demyelinating neuropathy. PMID- 7870117 TI - Sensory testing is different in laboratory personnel compared with paid volunteers. PMID- 7870118 TI - Multiple tests and diagnostic validity. PMID- 7870119 TI - Assessment of different reference limits for turn/amplitude parameters. PMID- 7870120 TI - Persistent painful Lyme radiculoneuritis. PMID- 7870121 TI - Osteomalacic myopathy. PMID- 7870122 TI - Further observations on myotonia related to malignancy. PMID- 7870123 TI - Effects of antimalarials and protease inhibitors on plasmodial hemozoin production. AB - Malarial hemozoin may play an important role as a target for antimalarial drugs and in disease pathogenesis. A new assay for hemozoin was developed in which the hemozoin was separated from cells by filtration. Trophozoites have substantially more hemozoin than rings, but there are relatively small differences between chloroquine-sensitive and chloroquine-resistant strains. The effects of hemozoin content of chloroquine and artemisinin, two antimalarial drugs, and E64 and Pepstatin A, two protease inhibitors, were measured. At concentrations at which hypoxanthine incorporation was unaffected, the hemozoin content of rings was decreased by E64, but not by the other three compounds. Artemisinin and Pepstatin A also had little effect on the hemozoin content of trophozoites. Chloroquine and E64 inhibited trophozoite hemozoin formation, but inhibited hypoxanthine uptake to a similar or greater extent. When either rings or trophozoites were exposed to several higher concentrations of chloroquine, hemozoin content was diminished, but significantly less than hypoxanthine uptake. Various concentrations of E64, in contrast, inhibited hemozoin production by both rings and trophozoites significantly more than hypoxanthine incorporation, suggesting that hemozoin production may be directly affected by E64. PMID- 7870124 TI - Distribution of parasite cysteine proteinases in lesions of mice infected with Leishmania mexicana amastigotes. AB - It is well established that Leishmania mexicana amastigotes contain large amounts of cysteine proteinases in their extended lysosomes. In this study it is shown that the cell-free supernatant of homogenized lesion tissue from infected mice contains large amounts of acid proteinases. The majority of this enzymatic activity also corresponds to cysteine proteinases from L. mexicana amastigotes. Immunoelectron microscopy of mouse lesion sections suggests, that frequently amastigotes lyse and release lysosomal cysteine proteinases into the parasitophorous vacuole of infected macrophages. The cysteine proteinases are also found extracellularly in the tissue presumably as a result of macrophage rupture and appear to persist in the lesion tissue, where they may damage host cells and the extracellular matrix. PMID- 7870125 TI - Nucleotide sequence organisation and analysis of the nuclear ribosomal DNA circle of the protozoan parasite Entamoeba histolytica. AB - We have sequenced the extrachromsomal ribosomal DNA (rDNA) circle of the human protozoan parasite Entamoeba histolytica HM-1:IMSS and present here the complete sequence organisation of the 24.5-kb molecule. Each circle contains two 5.9-kb rDNA transcription units organised as inverted repeats. The regions downstream (3543 bp) and upstream (9216 bp) of the rDNAs contain various families of short tandem repeats. Some of the upstream repeats share extensive sequence homology with the downstream repeats. In addition to the rDNAs themselves, the rDNA circle appears to code for only one other transcript which is 0.7 kb in size as seen in Northern blots. From DNA sequence analysis, no open reading frame could be assigned to the transcript. Extrachromosomal rDNA circles also exist in other E. histolytica strains. Restriction enzyme maps of rDNA circles were constructed from E. histolytica strains 200:NIH, HK-9 and Rahman; and Entamoeba moshkovskii strain Laredo. Striking differences were observed in the organisation of some of them, e.g. the HK-9, Rahman and Laredo circles contained only one rDNA unit and lacked the 0.7-kb transcript sequence. The short repeat sequences upstream and downstream of rDNAs were present in HK-9 and Rahman but absent in Laredo. Circles with one rDNA unit may be derived from those with two units by homologous recombination at direct repeat sequences located upstream and downstream of the two rDNAs. PMID- 7870126 TI - A Taenia crassiceps cDNA sequence encoding a putative immunodiagnostic antigen for bovine cysticercosis. AB - A cDNA expression library was constructed in lambda gt11 using poly A mRNA from the metacestode stage of Taenia crassiceps. The library was screened with rabbit antiserum to a previously defined protein fraction from Taenia hydatigena immunodiagnostic for bovine cysticercosis and with sera from cattle with experimentally induced cysticercosis. One clone (lambda TcA2) containing a 279-bp cDNA insert, reacted strongly with both antisera. A second clone (lambda TcA5.5) revealed the full-length cDNA sequence to be 361 bp. Data from Southern blots and enzymatically amplified genomic DNA segments were consistent with multiple copies or a gene family within the genome. The lambda TcA2 cDNA insert was subcloned into the plasmid pPR987 which generated a 47-kDa maltose-binding fusion protein (TcA2-MBP). Affinity-purified TcA2-MBP antigen reacted positively by ELISA with sera from cattle with experimentally induced T. saginata infections but not with sera from cattle with Fasciola hepatica or common gastrointestinal parasite infections. Rabbit polyclonal, monospecific antisera to TcA2-MBP recognized a 10 kDa protein in the cyst fluid, body wall and excretory/secretory products of the metacestode stage of T. crassiceps and immonolocalized this protein to organelles within the matrix of the cyst wall. PMID- 7870127 TI - Failure to detect Trichinella spiralis p43 in isolated host nuclei and in irradiated larvae of infected muscle cells which express the infected cell phenotype. AB - Infection by Trichinella spiralis induces host muscle cells to become repositioned within the cell cycle and to lose differentiated skeletal muscle characteristics. Antibodies to a 43-kDa excretory-secretory (ES) protein (p43) also bind to infected host cell nuclei. Neither the identity of these nuclear antigens nor their role in inducing the infected cell phenotype is known. To address these issues, infected cell nuclei were isolated and nuclear antigens analyzed with several antibody preparations to p43. Four antibody preparations to p43 recognized 43-, 45-, 50-, 67- and 71-kDa proteins in ES extracts. The prominent proteins recognized by these antibodies in host nuclear antigen extracts were 71, 79, 86 and 97 kDa. Less prominent proteins of approximately 43 and 45 kDa were detected in nuclear extracts. However, antibodies which specifically recognized p43 failed to bind detectably with in situ and isolated host nuclei and nuclear extracts. Expression of p43 was analyzed in host cells infected by newborn larvae irradiated with 60Co. This treatment prevented expression of detectable levels of p43 in resulting muscle larvae, while infected muscle cells displayed typical infected cell characteristics. However, anti-p43 antibodies which recognized multiple ES and nuclear proteins did stain nuclei of irradiated larva-infected cells, albeit at reduced levels. The results raise doubts that p43 is required for induction of the infected cell phenotype. Nevertheless, nuclear antigens recognized by anti-p53 antibodies remain as candidates for influencing this phenotype. PMID- 7870128 TI - Photoaffinity labelling of Plasmodium falciparum proteins involved in phospholipid transport. AB - Erythrocytes infected with mature-stage malaria parasites accumulate phospholipids from exogenous sources. We show that the transport of N-(7 nitrobenzy-2-oxa-1,3-diazol-4-yl)-1,2- dipalmitoyl-sn-glycero-3 phosphatidylethanolamine (N-NBD-DPPE), from the erythrocyte membrane to the intracellular malaria parasite, is dependent upon metabolic energy. A photoreactive phospholipid analogue, N-[125I]iodo-4-azidosalicylamidyl-1, 2 dilauryl-sn-glycero-3-phosphatidylethanolamine (N-125I-ASA-DLPE), has been synthesised and used in an attempt to identify proteins involved in phospholipid trafficking in malaria-infected erythrocytes. This photoreactive probe was found to preferentially label a protein with an apparent molecular weight of 22 kDa. Photolabelling of the 22-kDa protein was enhanced upon ATP depletion of malaria infected erythrocytes. PMID- 7870129 TI - Kinetoplast DNA from Trypanosoma rangeli contains two distinct classes of minicircles with different size and molecular organization. AB - Trypanosomatids are characterized by the presence of kinetoplast DNA (kDNA), a peculiar form of mitochondrial DNA that consists of several thousand minicircles and a few dozen maxicircles catenated in a network. Within a species, the minicircles are known to differ in nucleotide sequence, but are homogeneous in size and always cross-hybridize. In all species of trypanosomatids, kDNA minicircles have at least one copy of a conserved 100-200 nucleotide region containing an almost invariant 'universal' 12-mer sequence (5'-GGGGTTGGTGTA-3'). We here report that Trypanosoma rangeli, a non-pathogenic parasite of man, contains two distinct classes of kDNA, minicircles called KP1 and KP2, which differ in size and molecular organization. Both were cloned and sequenced in both directions. KP2 was 1587 bases along and contained two copies of the conserved region as direct repeats 180 degrees apart. In contrast, KP1 had 1764 bases and showed a single conserved region. Moreover, KP1 differed further from KP2 and from most other previously sequenced trypanosomatid minicircles by containing a nucleotide substitution (5'-GGGGTTAGTGTA-3') in the 12-mer universal sequence tag. Polymerase chain reaction and hybridization studies suggest that the sequence of KP1 is very conserved in several other T. rangeli strains from Honduras, Colombia and Venezuela. It thus could provide a good target for the molecular diagnosis of infection with this parasite. PMID- 7870130 TI - Conservation of the Plasmodium falciparum sporozoite surface protein gene, STARP, in field isolates and distinct species of Plasmodium. AB - The extent of structural conservation of the Plasmodium falciparum sporozoite surface protein gene, STARP, recently characterized in the T9/96 clone, has been analyzed using the polymerase chain reaction. Results from Ivory Coast and Thai clones, field isolates originating from Brazil and Kenya and laboratory maintained strains strongly suggest that this gene has a highly conserved structure throughout this species. This structure includes a complex repetitive central domain consisting of a mosaic region followed by tandem 45-amino acid encoding (Rp45) and 10-amino acid-encoding (Rp10) repeat regions. Limited size variation in this domain appeared to result from highly localized duplication events in the Rp45 and Rp10 regions. No size variation was observed in the 5' and 3' coding non-repetitive regions, but minor size polymorphism was found in the single intron at the 5' end of the gene. No evidence was found of distinct families of polymorphic types, as has been observed with the blood-stage MSA-1, MSA-2 and S-antigens. The sequence of the STARP homologue in the phylogenetically close chimpanzee parasite, Plasmodium reichenowi, has also been elucidated and reveals high sequence conservation, although interesting differences were detected in the composition of the Rp10 region, known in P. falciparum to contain B- and T-cell epitopes. Finally, DNA hybridization reveals the presence in rodent malaria species of sequences containing homology to the STARP non-repetitive (though not the repetitive) regions, which would suggest that a similar, conserved gene may exist in these species. PMID- 7870132 TI - Induction of the iron-containing superoxide dismutase in Entamoeba histolytica by a superoxide anion-generating system or by iron chelation. AB - The regulation of superoxide dismutase (SOD) expression was studied in 4 Entamoeba histolytica isolates. In comparison to anaerobic conditions, cultivation of the amoebae in the presence of superoxide radical anions or a ferrous iron chelator revealed substantial increase of SOD expression. Under the different culture conditions, all SOD activity could be exclusively attributed to an iron-containing type (FeSOD). Northern blot analysis revealed that FeSOD expression was regulated on the transcriptional level. Within the 5'-flanking region of the amoebic FeSOD gene, a 19-bp fragment was found with 68% sequence identity to the consensus motif of the binding site for the ferric uptake regulation gene product of Escherichia coli. Electrophoretic mobility shift assays with this 19-bp fragment and with amoebic nuclear extracts revealed specific DNA/protein complex formation. The results indicate that the regulation of E. histolytica FeSOD expression is similar to that of the manganese-containing SOD (MnSOD) of E. coli. PMID- 7870131 TI - Subcellular distribution and characterization of glucosephosphate isomerase in Leishmania mexicana mexicana. AB - The glycolytic enzyme glucosephosphate isomerase (PGI) is present in two different cell compartments of Leishmania mexicana promastigotes; more than 90% of the activity was detected in the cytosol, the remainder in glycosomes. This subcellular distribution contrasts with that in Trypanosoma brucei, in which the enzyme activity has been mainly located in the glycosomes. PGI was partially purified from L. mexicana cell extracts. Throughout the purification procedure only one single PGI activity could be detected. The partially purified protein had the same subunit molecular mass (65 kDa) as the previously characterized glycosomal protein of T. brucei. Both proteins were also very similar with respect to their kinetic and antigenic properties. Using the T. brucei glycosomal PGI gene as a hybridization probe, we cloned the corresponding gene of L. mexicana. Only a single PGI locus could be detected in the L. mexicana genome. Characterization of the cloned gene showed that it codes for a polypeptide of 604 amino acids, with a molecular mass of 67,113. The sequences of the Leishmania and Trypanosoma polypeptides are 69% identical. They differ in calculated net charge (-8 versus -2, respectively) and isoelectric point (6.65 versus 7.35). Our data strongly suggest that the PGI activity in the two cell compartments of L. mexicana and T. brucei is not attributable to different isoenzymes. We discuss the possible metabolic function of the highly different enzyme distribution in the two organisms, and the molecular mechanism that could be responsible for it. PMID- 7870134 TI - Characterization of a Trypanosoma cruzi poly(A)-binding protein and its genes. AB - We have characterized the biochemical properties of a 66-kDa poly(A)-binding protein (PABP1) in the protozoan Trypanosoma cruzi and isolated two classes of cDNAs encoding the protein. In concordance, Southern blots showed the presence of 2 gene copies. The two cDNA classes differ in the length of adenosine-rich segments in the 5' untranslated region and in point changes scattered throughout the sequence, but their 1650-bp open reading frames encode identical proteins. A single mRNA of 5.5 kb was detected, indicating that the noncoding regions are unusually long. Both the mRNA and the protein are constitutively expressed in all stages of T. cruzi life cycle. The biochemical properties and sequence comparisons show that the T. cruzi PABP1 is similar to the PABP1 of other eukaryotic organisms. These results indicate that PABP1 has been conserved throughout eukaryotic evolution. PMID- 7870135 TI - Inhibition of Trypanosoma cruzi trypanothione reductase by crystal violet. AB - A trypanothione reductase activity is present in all the main differentiation stages of Trypanosoma cruzi, amastigotes having the highest activity, and trypomastigotes the lowest. Trypanothione reductase could not be induced in epimastigotes exposed to H2O2. The trypanocidal drug crystal violet was a potent inhibitor of T. cruzi trypanothione reductase in vitro. The inhibition was competitive with respect to trypanothione with a Ki of 5.3 +/- 0.5 microM, uncompetitive with NADPH, and increased below pH 7.0 and above pH 8.0. Crystal violet, however, was not able to decrease the level of total reduced thiols in intact cells. Dihydrotrypanothione but not reduced glutathione, protected the enzyme from inhibition by crystal violet. PMID- 7870133 TI - Pyruvate dehydrogenase complexes from the equine nematode, Parascaris equorum, and the canine cestode, Dipylidium caninum, helminths exhibiting anaerobic mitochondrial metabolism. AB - The pyruvate dehydrogenase complex (PDC) has been purified to apparent homogeneity from 2 parasitic helminths exhibiting anaerobic mitochondrial metabolism, the equine nematode, Parascaris equorum, and the canine cestode, Dipylidium caninum. The P. equorum PDC yielded 7 major bands when separated by SDS-PAGE. The bands of 72, 55-53.5, 41 and 36 kDa corresponded to E2, E3, E1 alpha and E1 beta, respectively. The complex also contained additional unidentified proteins of 43 and 45 kDa. Incubation of the complex with [2 14C]pyruvate resulted in the acetylation of only E2. These results suggest that the P. equorum PDC lacks protein X and exhibits an altered subunit composition, as has been described previously for the PDC of the related nematode, Ascaris suum. In contrast, the D. caninum PDC yielded only four major bands after SDS PAGE of 59, 58, 39 and 34 kDa, which corresponded to E3, E2, E1 alpha and E1 beta, respectively. Incubation of the D. caninum complex with [2-14C]pyruvate resulted in the acetylation of E2 and a second protein which comigrated with E3, suggesting that the D. caninum complex contained protein X and had a subunit composition similar to PDCs from other eukaryotic organisms. Both helminth complexes appeared less sensitive to inhibition by elevated NADH/NAD+ ratios than complexes isolated from aerobic organisms, as would be predicted for PDCs from organisms exploiting microaerobic habitats. These results suggest that although these helminths have similar anaerobic mitochondrial pathways, they contain significantly different PDCs. PMID- 7870136 TI - Aerobic and anaerobic glucose metabolism of Phytomonas sp. isolated from Euphorbia characias. AB - Metabolic studies on Phytomonas sp. isolated from the lactiferous tubes of the latex-bearing spurge Euphorbia characias indicate that glucose is the preferred energy and carbon substrate during logarithmic growth. In stationary phase cells glucose consumption was dramatically reduced. Glucose consumption and end-product formation were measured on logarithmically growing cells, both under aerobic (air and 95% O2/5% CO2) and anaerobic (95% N2/5% CO2 and 100% N2) conditions. The rate of glucose consumption slightly increased under anaerobic conditions indicating that Phytomonas lacks a 'reverse Pasteur' effect contrary to the situation encountered in Leishmania major. Major end-products of glucose catabolism under aerobic conditions, detected by enzymatic and NMR measurements, were acetate, ethanol and carbon dioxide and under anaerobic conditions ethanol, glycerol and carbon dioxide. Smaller amounts of pyruvate, succinate, L-malate, L-lactate, phosphoenolpyruvate, alanine and aspartate were also detected. PMID- 7870137 TI - Identification of new cysteine protease gene isoforms in Trypanosoma cruzi. PMID- 7870138 TI - Cloning and characterisation of a Plasmodium falciparum homologue of the Ran/TC4 signal transducing GTPase involved in cell cycle control. PMID- 7870139 TI - Clearance of HIV infection in a perinatally infected infant. AB - BACKGROUND: We describe a child who was identified shortly after birth as infected with the human immunodeficiency virus type 1 (HIV-1), but whose infection appears to have completely cleared. Asymptomatic HIV-1 infection was diagnosed in the mother during the fourth month of pregnancy. The infant was delivered vaginally at 36 weeks, received no blood products, and was not breast fed. METHODS AND RESULTS: HIV-1 was detected by culture of the infant's peripheral-blood mononuclear cells at 19 and 51 days of age. Plasma from the infant was also culture-positive for HIV-1 at 51 days of age by DNA polymerase chain reaction (PCR). Nucleotide-sequence analysis of HIV-1 DNA showed extremely close homology of the cultures obtained 32 days apart, and forensic markers of genetic identity for the two cultures were identical. Hence, inadvertent viral contamination or error in the collection of specimens was highly unlikely. At 12 months of age the infant was seronegative for HIV-1, and numerous subsequent cultures and tests by PCR have also been negative for HIV-1. The child is five years of age at this writing, is HIV-seronegative, and remains well, with normal growth and development and no laboratory or clinical evidence of HIV-1 infection. CONCLUSIONS: The infant we describe was infected perinatally with HIV-1, but the infection subsequently cleared and the infant remained without detectable HIV-1 infection five years later. PMID- 7870140 TI - The infectivity of Cryptosporidium parvum in healthy volunteers. AB - BACKGROUND: Small numbers of Cryptosporidium parvum oocysts can contaminate even treated drinking water, and ingestion of oocysts can cause diarrheal disease in normal as well as immunocompromised hosts. Since the number of organisms necessary to cause infection in humans is unknown, we performed a study to determine the infective dose of the parasite in healthy adults. METHODS: After providing informed consent, 29 healthy volunteers without evidence of previous C. parvum infection, as determined by the absence of anti-cryptosporidium-specific antibodies, were given a single dose of 30 to 1 million C. parvum oocysts obtained from a calf. They were then monitored for oocyst excretion and clinical illness for eight weeks. Household contacts were monitored for secondary spread. RESULTS: Of the 16 subjects who received an intended dose of 300 or more oocysts, 14 (88 percent) became infected. After a dose of 30 oocysts, one of five subjects (20 percent) became infected, whereas at a dose of 1000 or more oocysts, seven of seven became infected. The median infective dose, calculated by linear regression, was 132 oocysts. Of the 18 subjects who excreted oocysts after the challenge dose, 11 had enteric symptoms and 7 (39 percent) had clinical cryptosporidiosis, consisting of diarrhea plus at least one other enteric symptom. All recovered, and there were no secondary cases of diarrhea among household contacts. CONCLUSIONS: In healthy adults with no serologic evidence of past infection with C. parvum, a low dose of C. parvum oocysts is sufficient to cause infection. PMID- 7870141 TI - Images in clinical medicine. Shock delivered by an implantable cardioverter defibrillator in response to spontaneous ventricular fibrillation. PMID- 7870142 TI - Screening for colorectal cancer. AB - In the past few years, knowledge of the clinical, biologic, and molecular genetic characteristics of colorectal cancer has greatly increased. Although the most cost-effective approach remains to be identified, screening for colorectal cancer can decrease mortality due to this disease by detecting cancers at earlier stages and allowing the removal of adenomas, thus preventing the subsequent development of cancer. Molecular studies that have helped define the genetic basis for this disease hold great promise for the development of better and more powerful methods to identify populations at risk. Individually, these technological, clinical, and basic-science advances are exciting; together, they promise to move us closer to the goal of substantially reducing mortality due to colorectal cancer. PMID- 7870143 TI - Inhaled glucocorticoids for asthma. PMID- 7870144 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-1995. A 56-year-old woman with abdominal pain, anemia, and a pelvic mass. PMID- 7870145 TI - Clearance of HIV--lessons from newborns. PMID- 7870146 TI - Colon-cancer genes and brain tumors. PMID- 7870147 TI - Airway inflammation in cystic fibrosis. PMID- 7870148 TI - Coronary angioplasty compared with bypass grafting. PMID- 7870149 TI - Coronary angioplasty compared with bypass grafting. PMID- 7870150 TI - Coronary angioplasty compared with bypass grafting. PMID- 7870151 TI - Coronary angioplasty compared with bypass grafting. PMID- 7870152 TI - Ethical issues in the use of zidovudine to reduce vertical transmission of HIV. PMID- 7870153 TI - Ethical issues in the use of zidovudine to reduce vertical transmission of HIV. PMID- 7870154 TI - Ethical issues in the use of zidovudine to reduce vertical transmission of HIV. PMID- 7870155 TI - Alcohol-related automobile crashes. PMID- 7870156 TI - Meningitis due to ceftriaxone-resistant Streptococcus pneumoniae. PMID- 7870158 TI - The dangers of carbon monoxide. PMID- 7870159 TI - The dangers of carbon monoxide. PMID- 7870157 TI - The dangers of carbon monoxide. PMID- 7870160 TI - Race plus IQ does not equal science. PMID- 7870161 TI - Truth is the daughter of time. PMID- 7870162 TI - Truth is the daughter of time. PMID- 7870163 TI - Molecular evolution. Active ancestral molecules. PMID- 7870164 TI - Muscle. Give in the filaments. PMID- 7870166 TI - Mergers mean risks. PMID- 7870165 TI - Antibody structure. The duck's dilemma. PMID- 7870167 TI - Dorsoventral axis inversion? PMID- 7870168 TI - AIDS activists seek speedy access to protease drugs.... PMID- 7870169 TI - Glaxo move seen as 'unavoidable'. PMID- 7870170 TI - Wellcome Trust to launch transfer company. PMID- 7870171 TI - Defective myosin VIIA gene responsible for Usher syndrome type 1B. AB - Usher syndrome represents the association of a hearing impairment with retinitis pigmentosa and is the most frequent cause of deaf-blindness in humans. It is inherited as an autosomal recessive trait which is clinically and genetically heterogeneous. Some patients show abnormal organization of microtubules in the axoneme of their photoreceptors cells (connecting cilium), nasal ciliar cells and sperm cells, as well as widespread degeneration of the organ of Corti. Usher syndrome type 1 (USH1) is characterized by a profound congenital sensorineural hearing loss, constant vestibular dysfunction and prepubertal onset of retinitis pigmentosa. Of three different genes responsible for USH1. USH1B maps to 11q13.5 (ref. 10) and accounts for about 75% of USH1 patients. The mouse deafness shaker 1 (sh1) mutation has been localized to the homologous murine region. Taking into account the cytoskeletal abnormalities in USH patients, the identification of a gene encoding an unconventional myosin as a candidate for shaker-1 (ref. 14) led us to consider the human homologue as a good candidate for the gene that is defective in USH1B. Here we present evidence that a gene encoding myosin VIIA is responsible for USH1B. Two different premature stop codons, a six-base-pair deletion and two different missense mutations were detected in five unrelated families. In one of these families, the mutations were identified in both alleles. These mutations, which are located at the amino-terminal end of the motor domain of the protein, are likely to result in the absence of a functional protein. Thus USH1B appears as a primary cytoskeletal protein defect. These results implicate the genes encoding other unconventional myosins and their interacting proteins as candidates for other genetic forms of Usher syndrome. PMID- 7870172 TI - A type VII myosin encoded by the mouse deafness gene shaker-1. AB - Genetic deafness is common, affecting about 1 in 2,000 births. Many of these show primary abnormalities of the sensory neuroepithelia of the inner ear, as do several hearing-impaired mouse mutants, suggesting that genes involved in sensory transduction could be affected. Here we report the identification of one such gene, the mouse shaker-1 (sh1) gene. Shaker-1 homozygotes show hyperactivity, head-tossing and circling due to vestibular dysfunction, together with typical neuroepithelial-type cochlear defects involving dysfunction and progressive degeneration of the organ of Corti. The sh1 gene encodes an unconventional myosin molecule of the type VII family. Three mutations are described, two mis-sense mutations and a splice acceptor site mutation, all in the region encoding the myosin head. The myosin type VII molecule encoded by sh1 is the first molecule to be identified that is known, by virtue of its mutations, to be involved in auditory transduction. PMID- 7870173 TI - Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain. AB - Nicotine affects many aspects of behaviour including learning and memory through its interaction with neuronal nicotinic acetylcholine receptors (nAChR). Functional nAChRs are pentameric proteins containing at least one type of alpha subunit and one type of beta-subunit. The involvement of a particular neuronal nicotinic subunit in pharmacology and behaviour was examined using gene targeting to mutate beta 2, the most widely expressed nAChR subunit in the central nervous system. We report here that high-affinity binding sites for nicotine are absent from the brains of mice homozygous for the beta 2-subunit mutation. Further, electrophysiological recording from brain slices reveals that thalamic neurons from these mice do not respond to nicotine application. Finally, behavioural tests demonstrate that nicotine no longer augments the performance of beta 2-1- mice on passive avoidance, a test of associative memory. Paradoxically, mutant mice are able to perform better than their non-mutant siblings on this task. PMID- 7870174 TI - Immunological function of a defined T-cell population tolerized to low-affinity self antigens. AB - In the thymus there are two major mechanisms of T-lymphocyte tolerance: clonal deletion and clonal inactivation. One important problem underlying the mechanism of clonal inactivation is why unresponsive cells are maintained in the mature peripheral T-cell repertoire. Here we report that transgenic alpha beta T-cells may be tolerized to a self antigen Mls-1a, but still retain proliferative responses for alternative peptide antigens and superantigens. These self-tolerant T cells can also provide immunopathological and memory cytotoxic function in vivo. We propose that high-affinity/avidity self-reactive T cells are deleted in the thymus, whereas lower-affinity/avidity interactions lead to unresponsiveness and define the 'resting threshold' for a given T cell. These low-affinity self tolerant T cells remain functionally competent for high-affinity foreign antigens, and efficiently eliminate natural pathogens in vivo. PMID- 7870175 TI - US stalls over tests of marijuana to treat AIDS patients. PMID- 7870176 TI - An HMG-box-containing T-cell factor required for thymocyte differentiation. AB - Two candidate genes for controlling thymocyte differentiation, T-cell factor-1 (Tcf-1) and lymphoid enhancer-binding factor (Lef-1), encode closely related DNA binding HMG-box proteins. Their expression pattern is complex and largely overlapping during embryogenesis, yet restricted to lymphocytes postnatally. Here we generate two independent germline mutations in Tcf-1 and find that thymocyte development in (otherwise normal) mutant mice is blocked at the transition from the CD8+, immature single-positive to the CD4+/CD8+ double-positive stage. In contrast to wild-type mice, most of the immature single-positive cells in the mutants are not in the cell cycle and the number of immunocompetent T cells in peripheral lymphoid organs is reduced. We conclude that Tcf-1 controls an essential step in thymocyte differentiation. PMID- 7870177 TI - Editing of glutamate receptor subunit B pre-mRNA in vitro by site-specific deamination of adenosine. AB - Editing of the glutamate receptor subunit B (GluR-B) pre-mRNA at a single adenosine residue results in an amino-acid change that profoundly alters the electrophysiological properties of the receptor. Here we show that the GluR-B pre mRNA is efficiently and accurately edited in vitro, and that base-pair interactions between the editing site and a sequence in the downstream intron are required for substrate recognition. In addition, we directly demonstrate that editing results from the conversion of adenosine to inosine by enzymatic deamination. The biochemical properties of this GluR-B editing activity are similar to those of a double-stranded-RNA-dependent adenosine deaminase, but RNA competition and column fractionation experiments indicate that the GluR-B editing and deaminase activities are distinct. Thus, the GluR-B editing enzyme may contain the adenosine deaminase, or a similar activity, and an RNA recognition subunit that specifically targets the enzyme to the editing site. PMID- 7870178 TI - A family of transcriptional adaptor proteins targeted by the E1A oncoprotein. AB - The cellular protein p300 is a target of the adenoviral E1A oncoprotein and is thought to participate in preventing the G0/G1 transition in the cell cycle, activating certain enhancers and stimulating differentiation pathways. CBP is a protein that is associated with and coactivates the transcription factor CREB, mediating the induction by cyclic AMP of certain responsive promoters. The sequences of p300 and CBP are highly related. We show here that p300, like CBP2, can stimulate transcription. This activity is directly and specifically inhibited by E1A. We also find that CBP exists in a DNA-bound complex containing a member of the CREB family and that E1A and CBP interact with one another in vivo. In keeping with the idea that E1A functionally targets CBP, cAMP-dependent transcription is repressed by E1A. Thus, p300 and CBP define a family of transcriptional adaptor proteins that are specifically targeted by the E1A oncoprotein. PMID- 7870179 TI - Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. AB - The 265K nuclear protein CBP was initially identified as a co-activator for the protein kinase A (PKA)-phosphorylated form of the transcription factor CREB. The domains in CBP that are involved in CREB binding and transcriptional activation are highly related to the adenoviral E1A-associated cellular protein p300 (refs 2, 3), and to two hypothetical proteins from Caenorhabditis elegans, R10E11.1 and K03H1.10 (refs 4 and 5, respectively), whose functions are unknown. Here, we show that CBP and p300 have similar binding affinity for the PKA-phosphorylated form of CREB, and that p300 can substitute for CBP in potentiating CREB-activated gene expression. We find that E1A binds to CBP through a domain conserved with p300 and represses the CREB-dependent co-activator functions of both CBP and p300. Our results indicate that the gene repression and cell immortalization functions associated with E1A involve the inactivation of a family of related proteins that normally participate in second-messenger-regulated gene expression. PMID- 7870180 TI - A highly conserved ATPase protein as a mediator between acidic activation domains and the TATA-binding protein. AB - Biochemical and genetic studies suggest the existence of mediators that work between the activation domains (ADs) of regulatory proteins and the basic transcriptional machinery. We have previously shown genetically that Sug1 interacts with the AD of the yeast activator Ga14. Here we provide evidence that the Sug1 protein of yeast binds directly to the ADs of Ga14 and the viral activator, VP16. Sug1 protein is associated with the TATA-binding protein in vivo and binds to it in vitro, consistent with a mediator function. We also demonstrate that Sug1 is not a component of the 26S proteasome, contrary to previous reports. Sug1 is a member of a large, highly conserved family of ATPases, implying a role for ATP hydrolysis in the activation of transcription. PMID- 7870181 TI - Interaction of thyroid-hormone receptor with a conserved transcriptional mediator. AB - The thyroid-hormone receptors are hormone-dependent transcription factors that control expression of many target genes. This regulation is presumably a consequence of hormone-dependent contacts between the receptors and the basal transcription machinery. We used the yeast two-hybrid system to identify a candidate human transcriptional mediator that interacts with both the thyroid hormone receptor and the retinoid-X receptor in a ligand-dependent fashion. This protein, Trip1 (for thyroid-hormone-receptor interacting protein), shares striking sequence conservation with the yeast transcriptional mediator Sug1 (refs 6, 7). Here we show that Trip1 can functionally substitute for Sug1 in yeast, and that both proteins interact in vitro with the thyroid-hormone receptor, and with the transcriptional activation domains of yeast GAL4 and of herpes virus VP16. PMID- 7870184 TI - Beta-adrenoceptor-mediated facilitation of endogenous noradrenaline release from rat isolated trachea. AB - Overflow of endogenous noradrenaline from rat isolated trachea was evoked by electrical field stimulation (3 Hz, 540 pulses) in the presence of yohimbine, desipramine and tyrosine. Isoprenaline 100 nmol/l increased the evoked overflow of noradrenaline by about 65%. This effect was antagonized by propranolol (100 nmol/l) and the beta 2-selective adrenoceptor antagonist ICI 118,551 (100 nmol/l), but not by the beta 1-selective adrenoceptor antagonist CGP 20712 A (100 nmol/l). The beta 2-selective adrenoceptor agonist formoterol (1-100 nmol/l) also facilitated the evoked overflow of noradrenaline, but maximally by only about 25% at 10 nmol/l, i.e. formoterol behaved as a partial agonist at these facilitatory beta-adrenoceptor. This assumption is also supported by the observation that formoterol (10 nmol/l) acted as antagonist against isoprenaline (100 nmol/l). Mechanical removal of the mucosa resulted in a 30% decrease in tissue noradrenaline and a 55% reduction of the evoked overflow of noradrenaline. In mucosa-denuded preparations isoprenaline failed to facilitate noradrenaline overflow. In the presence of indomethacin (3 mumol/l) the evoked overflow of noradrenaline from mucosa containing preparations was increased by about 50%, but isoprenaline still further facilitated the evoked noradrenaline overflow by about 40%. In conclusion, the overflow of noradrenaline in the rat trachea is facilitated via beta 2-adrenoceptors, an effect which requires an intact airway mucosa. PMID- 7870183 TI - Noradrenaline release from rat sympathetic neurons evoked by P2-purinoceptor activation. AB - The effects of ATP and analogues on the release of previously incorporated 3H noradrenaline were studied in cultured sympathetic neurons derived from superior cervical ganglia of neonatal rats. Electrical field stimulation (40 mA at 3 Hz) of the neurons for 10 s markedly enhanced the outflow of tritium. ATP applied for 5 s to 2 min at concentrations of 0.01 to 1 mmol/l caused a time- and concentration-dependent overflow with half maximal effects at about 10 s and 100 mumol/l, respectively. 2-Methylthio-ATP was equipotent to ATP in inducing 3H overflow. ADP (100 mumol/l), when applied for 2 min, also caused a small 3H overflow, but alpha, beta-methylene-ATP (100 mumol/l), AMP (100 mumol/l), R(-)N6 (2-phenylsiopropyl)-adenosine (R(-)-PIA; 10 mumol/l) and 5'-N ethylcarboxamidoadenosine (NECA; 1 mumol/l) did not. The 3H-overflow induced by 10 s applications of 100 mumol/l ATP was abolished by suramin (100 mumol/l) and reduced by about 70% by reactive blue 2 (3 mumol/l). Electrically evoked overflow, in contrast, was slightly enhanced by suramin, but not modified by reactive blue 2. Xanthine amine congener (10 mumol/l) and hexamethonium (10 mumol/l) did not alter ATP-evoked release. Removal of extracellular Ca2+ from the medium reduced ATP- and electrically induced overflow by about 95%. Tetrodotoxin (1 mumol/l) abolished electrically evoked 3H-overflow but inhibited ATP-induced overflow by only 70%. The alpha 2-adrenoceptor agonist UK 14,304 at a concentration of 1 mumol/l diminished both electrically and ATP-evoked tritium overflow by approximately 70%. These results indicate that activation of P2 purinoceptors stimulates noradrenaline release from rat sympathetic neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870182 TI - Molecular pharmacology of somatostatin receptors. AB - The neuropeptide somatostatin (SRIF) is widely expressed in the brain and in the periphery in two main forms, SRIF-14 and SRIF-28. Similarly, the presence of SRIF receptors throughout the whole body has been reported. SRIF produces a variety of effects including modulation of hormone release (e.g. GH, glucagon, insulin), of neurotransmitter release (e.g. acetylcholine, dopamine, 5-HT), and its own release is modulated by many neurotransmitters. SRIF affects cognitive and behavioural processes, the endocrine system, the gastrointestinal tract and the cardiovascular system and also has tumor growth inhibiting effects. Initially, two classes of SRIF receptors have been proposed on the basis of biochemical and functional studies. However, the recent cloning of five putative SRIF receptor subtypes which belong to the G-protein coupled receptor superfamily suggests that SRIF mediates its various effects via a whole family of receptors. Here we review, in this new context, the molecular pharmacology of the SRIF receptor subtypes present in the brain and in the periphery, and address the question of nomenclature of SRIF receptors. PMID- 7870185 TI - Muscarinic inhibition of endogenous noradrenaline release from rabbit isolated trachea: receptor subtype and receptor reserve. AB - The aim of the present study was to characterize putative muscarine receptors on sympathetic nerve terminals in the rabbit trachea. Release of endogenous noradrenaline from in vitro incubated rabbit trachea was evoked by electrical field stimulation (3 Hz, 540 pulses) and quantified by high performance liquid chromatography with electrochemical detection. The muscarine receptor agonist oxotremorine inhibited the evoked release of noradrenaline completely at 1 mumol/l (EC50: 64 nmol/l). The concentration response curve was very steep (Hill coefficient of 2.3). Scopolamine shifted the concentration response curve of oxotremorine to the right (-log KB 8.48) demonstrating specific, inhibitory muscarine receptors. Several subtype-preferring muscarine receptor antagonists also shifted the concentration response curve of oxotremorine to the right. The rank order of potency was (-log KB or pA2*): scopolamine (8.48) > AF-DX 384 (7.88*; slope of Schild plot 1.1) > (R)-trihexyphenidyl (7.87) > 4-DAMP (7.85) > AQ-RA 741 (7.77) >> methoctramine 6.18) > pirenzepine (6.0) > p-fluoro hexahydrosiladifenidol (p-FHHSiD, 5.68). When these affinity constants were plotted against reported -log Ki values determined in binding studies on human cloned muscarine receptor subtypes (m1-m5), the best correlation was obtained for m2. Indomethacin (3 mumol/l), which on its own increased the evoked noradrenaline release by about 45%, affected neither the inhibitory effect of oxotremorine nor the antagonistic potency of methoctramine or p-FHHSiD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870187 TI - The fade of the purinergic neurogenic contraction of the guinea-pig vas deferens: analysis of possible mechanisms. AB - The purinergic response of the guinea-pig vas deferens to long trains of pulses at high frequency consists of an initial twitch followed by a much lower plateau. Mechanical, neurochemical and electrophysiological techniques were used to examine the reason for the fade. Mechanical measurements. In tissues stimulated by trains of 180 pulses/10 Hz and treated with prazosin to suppress the noradrenergic contraction component, the response to alpha, beta-methylene ATP and to exogenous ATP was as high during the secondary plateau of the purinergic neurogenic contraction as it was outside electrical stimulation periods; the response to 50 pulses/100 Hz was also unchanged during the low plateau. The plateau was not increased by reactive blue 2,8-(p-sulphophenyl)theophylline, propranolol or capsaicin. Neurochemical measurements. In tissues preincubated with [3H]-noradrenaline, electrical stimulation elicited an overflow of tritium and of ATP. In the absence of drugs as well as in the presence of prazosin and suramin to suppress contractions, the overflow of tritium per pulse decreased slightly in the course of trains of 90 pulses/10 Hz; the overflow of ATP per pulse decreased to a greater extent on average, but the decrease was not statistically significant. In the presence of prazosin and nifedipine, also to suppress contractions, the overflow of tritium per pulse again decreased slightly in the course of trains of 105 pulses/10 Hz, but the overflow of ATP per pulse if anything tended to increase. Electrophysiological measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870186 TI - Presynaptic alpha 2A-adrenoceptors inhibit the release of endogenous dopamine in rabbit caudate nucleus slices. AB - alpha 2-Adrenoceptors modulating the release of dopamine were identified and characterized in slices of the head of the rabbit caudate nucleus. Release of endogenous dopamine was measured by fast cyclic voltammetry as the increase in the extracellular concentration of dopamine elicited by electrical stimulation. The electrochemical signal was identified as dopamine by means of the oxidation potential, the voltammogram and the fact that the signal was not changed by desipramine, which inhibits the high affinity uptake of noradrenaline, but was greatly increased by nomifensine, which in addition inhibits the high affinity uptake of dopamine. Stimulation by 6 pulses/100 Hz increased the extracellular concentration of dopamine by about 85 nM. The selective alpha 2-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) reduced this release with an EC50 of 173 nM and by maximally 75%. The alpha 2-adrenoceptor agonists clonidine and oxymetazoline only tended to cause a decrease. Six drugs, including oxymetazoline, were tested as antagonists against UK 14,304. Their order of antagonist potency (pKD values in brackets) was rauwolscine (8.0) > oxymetazoline (7.5) > 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101; 7.3) > phentolamine (7.1) > corynanthine (5.1) approximately prazosin (<6). Given alone, the antagonists did not change the release of dopamine elicited by 6 pulses/100 Hz, and the same was true for the dopamine receptor antagonist sulpiride. When caudate slices were stimulated by 10 pulses/1 Hz, sulpiride increased the release of dopamine. Desipramine and rauwolscine, in contrast, again caused no change. It is concluded that dopaminergic axons in the rabbit caudate nucleus possess release-inhibiting alpha 2-adrenoceptors.2+ off PMID- 7870188 TI - Release of ATP in rat vas deferens: origin and role of calcium. AB - Release of endogenous ATP elicited by electrical (neural) stimulation and exogenous agonists was studied in the rat isolated vas deferens. The aims were to dissect neural and postjunctional contributions to the nerve activity-evoked overflow of ATP and to clarify the role of transmitter receptors and calcium in postjunctional ATP release. In tissues preincubated with [3H]-noradrenaline, electrical stimulation (100 pulses/10 Hz) elicited contraction and an overflow of tritium and ATP. Contractions as well as ATP overflow were reduced by prazosin 0.3 microM and even more so by prazosin 0.3 microM combined with suramin 300 microM. They were also reduced by nifedipine 10 microM and even more so by nifedipine 10 microM combined with ryanodine 20 microM (the additional effect of ryanodine on ATP overflow was not significant). In tissues not pretreated with [3H]-noradrenaline, exogenous noradrenaline 10 microM and alpha,beta-methylene ATP 10 microM elicited contraction and an overflow of ATP. Responses to noradrenaline were blocked by prazosin 0.3 microM but not suramin 300 microM and were greatly reduced by nifedipine 10 microM and in Ca(2+)-free medium. Responses to alpha,beta-methylene ATP were blocked by suramin 300 microM but not prazosin 0.3 microM, were reduced by nifedipine 10 microM (effect on ATP overflow not significant) and were reduced even more in Ca(2+)-free medium. Neuropeptide Y 0.3 microM caused only very small contraction and ATP overflow. The electrically as well as the agonist-evoked ATP overflow correlated well with the contraction responses except in experiments with suramin which retarded the removal, by vas deferens tissue, of ATP from the medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870189 TI - Effect of desipramine-induced blockade of neuronal uptake mechanisms on adrenoceptor-mediated responses in the guinea-pig colon. AB - In order to clarify whether adrenoceptors in the guinea-pig distal colon are under sympathetic control, we assessed possible variations in the sensitivity to adrenoceptor agonists after blockade of neuronal catecholamine uptake mechanisms by desipramine (DMI). First, experiments were carried out to investigate the effects of DMI added in the organ bath on propulsion velocity, endogenous and [3H] prelabelled acetylcholine overflow, electrically evoked noradrenaline overflow and longitudinal smooth muscle tone. Secondly, we studied the effects of adrenoceptor agonists on the above parameters in untreated animals and in animals chronically treated with DMI. DMI added in the organ bath at concentrations equal to or higher than 30 nM inhibited all the parameters under study. Thus, when evaluating the effect of DMI on concentration-response curves to adrenoceptor agonists, concentrations which were per se inactive were used. DMI added in the organ bath at concentrations up to 30 nM potentiated the inhibitory effects of exogenous noradrenaline on propulsion velocity and acetylcholine overflow, but it did not affect the concentration-response curve to exogenous noradrenaline on longitudinal smooth muscle tone. Furthermore, 30 nM DMI inhibited propulsion velocity during sympathetic nerve stimulation. In preparations obtained from animals chronically treated with DMI, no significant change of propulsion velocity, endogenous and [3H] prelabelled acetylcholine overflow was found with respect to untreated animals. Nevertheless, in such preparations subsensitivity to isoprenaline (acting mainly on muscular beta-adrenoceptors) and clonidine (acting on neuronal alpha 2-adrenoceptors) and super-sensitivity to phenylephrine were observed. Electrically evoked noradrenaline overflow was enhanced, in a frequency-dependent way, by yohimbine and inhibited by clonidine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870190 TI - Agonist-induced down-regulation of the m4 muscarinic acetylcholine receptor occurs without changes in receptor mRNA steady-state levels. AB - The regulation of m4 muscarinic acetylcholine receptor mRNA expression by receptor activation was studied in N1E-115 neuroblastoma and AtT-20 pituitary cells that endogeneously express the m4 muscarinic receptor. Receptor concentration was measured by binding of the muscarinic receptor radioligand [3H]quinuclidinyl benzilate, and RNA-RNA solution hybridization/RNase protection assay with a m4 receptor-specific [32P]-cRNA probe was used to evaluate the levels of receptor mRNA. Treatment of both cell lines with a receptor-saturating concentration of the agonist carbachol decreased receptor number. However, there was no change in steady-state levels of m4 mAChR mRNA in both cell lines. Determination of mRNA stability in the presence of the transcription blocker actinomycin D revealed that carbachol treatment increased half-life of receptor mRNA in N1E-115 cells, but not in AtT-20 cells, suggesting that receptor activation can regulate m4 receptor mRNA stability dependently on cell type. Analysis of receptor degradation kinetics in the presence of the protein synthesis inhibitor cycloheximide showed that receptor down-regulation in N1E-115 and AtT-20 cells is sufficiently accounted for by increased receptor degradation. These results indicate than m4 muscarinic receptor down-regulation is substantially different from that of the muscarinic receptor subtypes m2 and m3 which is reported to be associated with agonist-induced reduction in receptor mRNA. PMID- 7870191 TI - Evidence that the presynaptic A2a-adenosine receptor of the rat motor nerve endings is positively coupled to adenylate cyclase. AB - The action of the A2a-adenosine analogue, CGS 21680C, on electrically evoked [3H]acetylcholine ([3H]-ACh) release, and its interaction with forskolin (an activator of adenylate cyclase), MDL 12,330A (an irreversible inhibitor of adenylate cyclase), rolipram (an inhibitor of cyclic AMP specific phosphodiesterase), dibutyryl- (db-cAMP) and 8-bromo- (8-Br-cAMP) cyclic AMP analogues (substances that mimic intracellular actions of cyclic AMP), were investigated using rat phrenic nerve-hemidiaphragm preparations. CGS 21680C facilitated [3H]-ACh release. Forskolin (but not 1,9-dideoxy forskolin), rolipram, db-cAMP and 8-Br-cAMP also increased evoked neurotransmitter release in a concentration-dependent manner. When the evoked [3H]-ACh release that is dependent on stimulation of the adenylate cyclase/cyclic AMP transduction system was supramaximally stimulated by these compounds, CGS 21680C (3 nmol/l) could not further increase [3H]-ACh release. Phosphodiesterase inhibition with low concentrations (< or = 30 mumol/l) of rolipram significantly potentiated the augmenting effect of CGS 21680C (1 nmol/l) on evoked [3H]-ACh release. MDL 12,330A (an irreversible inhibitor of adenylate cyclase) decreased evoked [3H] ACh release. The irreversible blocking action of MDL 12,330A on [3H]-ACh release was overcome by by-passing cyclase activation with db-cAMP and 8-Br-cAMP, but could not be overcome with FSK or CGS 21680C. The inhibitory effect of MDL 12,330A on evoked [3H]-ACh release was not mimicked by nifedipine. It is concluded that the increase in [3H]-ACh release caused by CGS 21680C results from activation of an A2a-adenosine receptor positively linked to the adenylate cyclase/cyclic AMP system. PMID- 7870192 TI - Effects of the centrally acting cholinesterase inhibitors tetrahydroaminoacridine and E2020 on the basal concentration of extracellular acetylcholine in the hippocampus of freely moving rats. AB - The effects of the centrally acting cholinesterase (ChE) inhibitors, tetrahydroaminoacridine (THA) and E2020 (1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2 yl] methylpiperidine hydrochloride), potential drugs for the treatment of senile dementia, on the basal extracellular acetylcholine (ACh) concentration in the hippocampus of freely moving rats, were determined using a microdialysis technique without the use of a ChE inhibitor in the perfusion fluid and a sensitive RIA. The mean (+/- SEM) basal ACh content in the perfusate was 103.1 +/ 3.6 fmol/sample collected over 30 min when microdialysis probes with a length of 3 mm dialysis membrane were used. The content of ACh decreased to an almost undetectable level upon perfusion of magnesium, suggesting that, in the present study, most of the ACh detected in the perfusates was due to cholinergic neuronal activity. THA (1.65 mg/kg, i.p.) produced an insignificant increase in the extracellular ACh concentration, but a dose of 5 mg/kg, i.p. caused a prolonged and significant 5.5-fold increase from the control value. E2020 (0.65 and 2 mg/kg, i.p.) produced significant, prolonged and dose-dependent increases (4 and 12 times the control value, respectively), the peak effect occurring within 1 h. Perfusion with 10 mumol/l physostigmine produced an about 30-fold increase of ACh output, suggesting that the basal extracellular ACh concentration is highly dependent on ChE activity. When ChE was inhibited locally by perfusion with physostigmine, THA (5 mg/kg) produced a transient and, at its maximum, a 1.42 fold increase in extracellular ACh concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870193 TI - Multiple mechanisms in the smooth muscle relaxant action of calcitonin gene related peptide (CGRP) in the guinea-pig ureter. AB - We have investigated the ability of human alpha CGRP (CGRP) to inhibit the electrically-evoked myogenic contractions of the guinea-pig ureter, in comparison with the K channel opener, cromakalim, and the adenylate cyclase activator, forskolin. CGRP (0.1 nM-0.1 microM) produced a concentration-dependent inhibition of the evoked contractions; its action was prevented by the CGRP receptor antagonist, CGRP(8-37) (1 microM), while it was unaffected by the nitric oxide (NO) synthase inhibitor, L-nitroarginine (30 microM). The effect of CGRP was antagonized in a noncompetitive manner (depression of Emax, no change in EC50) by glibenclamide (1-10 microM), a blocker of ATP-sensitive potassium channels (KATP). A substantial fraction of the inhibitory effect of CGRP was glibenclamide resistant, however. Glibenclamide also blocked the inhibitory action of cromakalim (0.1-10 microM) without affecting the inhibition produced by forskolin (0.1-30 microM). When tested in a low-K medium (extracellular K reduced from 5.9 to 1.2 mM), the inhibitory effects of CGRP, cromakalim and forskolin were enhanced. The inhibitory effect of forskolin was partly antagonized by glibenclamide when tested in a low-K medium. CGRP (0.1 microM), cromakalim (3 microM) and forskolin (10 microM) inhibited the contractile response to KCl (80 mM), which is characterized by a distinct phasic and tonic component: cromakalim selectively inhibited the phasic response to KCl with CGRP and forskolin inhibited both components. The inhibitory effect of CGRP on the phasic contraction to KCl was partly glibenclamide-(1 microM) sensitive, while that on the tonic contraction was glibenclamide-resistant. The inhibitory action of forskolin on both components of the response to KCl was unchanged by glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870195 TI - Differential effects of CGP 37849 and MK-801, competitive and noncompetitive NMDA antagonists, with respect to the modulation of sensorimotor gating and dopamine outflow in the prefrontal cortex of rats. AB - In the present study we compared effects of the competitive and non-competitive NMDA antagonists CGP 37849 and MK-801, respectively, on sensorimotor gating in rats, measured as prepulse-induced inhibition of the acoustic startle response, and the outflow of dopamine in the rat prefrontal cortex. CGP 37849 (10, 20 mg/kg), decreased the amplitude of the acoustic startle response, but was without effect on the prepulse-induced inhibition of the acoustic startle response. MK 801 (0.4 but not 0.2 mg/kg) enhanced the amplitude of the acoustic startle response and its doses of 0.2 and 0.4 mg/kg markedly attenuated the prepulse induced inhibition of the acoustic startle response. The effects of MK-801 (0.4 mg/kg) on the prepulse-induced inhibition of the acoustic startle response were not antagonized by the selective antagonists of D-2 and D-1 dopaminergic receptors, S(-)sulpiride (25 mg/kg) and SCH 23390 (0.1 mg/kg), respectively. When given alone, S(-)sulpiride attenuated the amplitude of the acoustic startle response and failed to altered the prepulse-induced inhibition of the acoustic startle response. SCH 23390 (0.1 mg/kg) failed to alter the amplitude and prepulse-induced inhibition of the acoustic startle response. The effects of CGP 37849 and MK-801 also differed with respect to dopamine outflow. MK-801 (0.2 and 0.4 mg/kg) enhanced the outflow of dopamine in the rat prefrontal cortex, while CGP 37849 (10 and 20 mg/kg) was without any effect on the extracellular concentration of dopamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870194 TI - Withdrawal from repeated morphine sensitizes mice to the striatal dopamine release enhancing effect of acute morphine. AB - The effects of morphine withdrawal and challenge on the alpha-methyl-rho-tyrosine (alpha MT)-induced depletion of dopamine (DA) as well as on DA metabolism and 3H SCH 23390 and 3H-spiperone binding were studied in the striata of male mice. Morphine was given s.c. 3 times daily for 5 days followed by 1 to 3 days' withdrawal. The alpha MT-induced DA depletion was retarded in mice withdrawn for 1 day from repeated morphine. At this time point the striatal concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) fell, too. In mice withdrawn for 3 days from morphine neither DA depletion nor DOPAC or HVA concentrations differed from those of control mice. In control mice acute morphine challenge accelerated the DA depletion at the dose 10 mg/kg but not at the dose 30 mg/kg. Both doses elevated striatal DOPAC and HVA. In mice withdrawn from repeated morphine for 1 day acute morphine partially counteracted the withdrawal-induced retardation of DA depletion and elevated striatal DOPAC and HVA clearly less than in control mice. However, in mice withdrawn for 3 days 10 mg/kg of morphine clearly enhanced DA depletion and its effect on striatal HVA was significantly augmented. In these mice as in controls the 30 mg/kg dose did not alter striatal DA depletion and elevated HVA less than in controls. Acute morphine did not alter striatal 3-methoxytyramine (3-MT) concentration in control mice but at the dose 10 mg/kg increased it in mice withdrawn for 3 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870196 TI - Phentolamine and hypoxia: modulation of contractility and alpha 1-adrenoceptors in isolated rat atria. AB - The hypoxia-induced effects on the binding sites and affinity constant of adrenoceptors, in the presence and absence of phentolamine, were determined for atrial membranes of hearts from normal and genetically hyperlipidaemic Yoshida (YOS) rats. Atrial function was also measured during normoxia and hypoxia, in the presence and absence of phentolamine. Hypoxia increased alpha 1-adrenoceptor density in atrial membranes of normal rats (Bmax 10.6 to 26.7 fmoles/mg protein). Phentolamine prevented the increase in the Bmax of alpha 1-adrenoceptors and increased the equilibrium dissociation constant of these receptors (KD 0.17 to 0.53 nmol/l). Beta-adrenoceptors did not change during hypoxia, but the Bmax was slightly increased (26%) in the presence of phentolamine. Thus, the alpha 1/beta ratio increased from 0.40 in normoxia to 1.06 in hypoxia. In normoxic atria from YOS rats, the alpha 1/beta ratio was already elevated (0.86) in comparison to control rats (mainly due to a higher density of alpha 1-adrenoceptors in atrial membranes from YOS rats). This ratio was not modified by hypoxia (0.84), but decreased when phentolamine was present (0.30). Hypoxia reduced the force of contraction and increased diastolic tension of atria of normal rats, while the sinus rate was not significantly modified. Phentolamine abolished the increase in diastolic tension and reduced the negative effect of hypoxia on contractile force. In YOS rat atria, functional parameters were modified by hypoxia in a qualitatively similar way to that of normal rat atria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870197 TI - Acute normovolaemic anaemia prevents ethanol-induced gastric damage in rats through a blood flow related mechanism. AB - The aim of the study was to assess whether changes in gastric mucosal blood flow induced by acute normovolaemic anaemia influence the susceptibility of the gastric mucosa to ethanol-induced damage, and the relationship of these changes with nitric oxide biosynthesis. Acute normovolaemic anaemia, promoted by exchanging 3 ml of blood by a plasma expander, induced a significant increase in gastric mucosal blood flow measured by hydrogen gas clearance, without changes in arterial blood pressure. After intragastric 60% ethanol administration, gastric blood flow was still significantly higher in anaemic than in control rats, and this was associated with a lower macroscopic and microscopic gastric damage. Following ethanol administration, anaemic rats pretreated with an inhibitor of nitric oxide biosynthesis (L-NMMA, 50 mg/kg, i.v.) had a lower gastric blood flow and a higher macroscopic gastric damage than anaemic rats without pretreatment. Anaemic rats pretreated with vasopressin also had after ethanol administration a lower gastric blood flow and a higher macroscopic gastric damage. It is concluded that acute normovolaemic anaemia protects the gastric mucosa against damage induced by intragastric ethanol. The inhibition of nitric oxide biosynthesis reverts in part this protective effect, and this seems to be related with the capability of nitric oxide to increase gastric mucosal blood flow, since vasoconstriction by a nitric oxide-independent mechanism causes a similar effect. PMID- 7870200 TI - Integrity in scientific writing. PMID- 7870198 TI - Sphinganine potentiation of cellular differentiation induced by various anti leukemia drugs in human leukemia cell line HL-60. AB - A slight induction of cellular differentiation (myelocytes and granulocytes) of HL-60 cells occurred after treatment with anti-tumor agents etoposide (VP-16), mitoxantrone (MXT), mitomycin C (MMC), actinomycin D (Act-D) or novobiocin (NOVO). Addition of sphinganine (SP), an inhibitor of protein kinase C (PKC) enhanced (2-3 fold) the VP-16, MXT, MMC or Act-D-induced differentiation but not the NOVO-induced differentiation. No induction of differentiation was observed with 5-fluorouracil (5-FU) in the absence or presence of SP. The addition of SP in the fresh medium after the removal of VP-16, MXT, or MMC (0.5 h treatment) enhanced the induction of differentiation. In contrast, SP post-treatment did not have any effect on enhancing the differentiation which was induced by Act-D short exposure (0.5 h). In an attempt to characterize the biochemical requirements for potentiation of VP-16-induced differentiation, we examined the effects of calcium depletion using calcium chelator ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) or calcium channel blocker verapamil. Potentiation of VP-16-induced differentiation by SP was not observed in EGTA- or verapamil-treated cells. Calcium supplementation to the cells during the treatment with EGTA restored the SP-potentiation of VP-16-induced differentiation. Our results also showed that the induction of differentiation was accompanied by a decrease in PKC activity (70% of the control). PKC activity decreased to a greater extent (50% of control) in SP potentiation of differentiation induction. Our results suggested that calcium-dependent biological action of antitumor agents and the inhibition of PKC activity are required for SP-potentiation of differentiation induction. PMID- 7870199 TI - The art of nursing continues. PMID- 7870201 TI - An exploratory study of associate degree nursing students' conceptual basis for caring practices. AB - Nursing educators, especially in associate degree nursing (ADN) programs, are confronted with the challenge of finding ways to include caring in practice. Recent studies provide guidance for incorporating caring behaviors into curricula, but little is known about students' definitions of care and what constitutes caring behaviors. The purposes of this exploratory study were to (1) describe students' definitions of caring and (2) determine how students know when they have cared for patients. ETHNOGRAPH was used to systematically group responses from a sample 117 first- and second-year nursing students from two programs. Students' descriptions of caring distinguished between meeting physical and psychosocial needs of patients, and depictions of actual caring behaviors. Students' responses to knowing when they cared for a patient fell in the categories of role performance, comfort, patient responses, and human needs gratification. Implications useful to educators in creating an environment where nursing students gain the skills necessary to further caring behaviors and practices are given. PMID- 7870202 TI - Economics and nursing. PMID- 7870203 TI - A progressive ventilator care unit: an alternative approach. AB - This article describes the development of a specialized unit for individuals requiring prolonged mechanical ventilation. The unit uses a collaborative approach to care, with the goal to provide quality care in a cost effective setting, and to facilitate transition to a more independent environment. PMID- 7870204 TI - Responses of clinical nurses about what is moral in nursing. PMID- 7870205 TI - A unique perspective on advanced practice nursing. AB - This article presents a working definition of the advanced practice registered nurse (APRN). The types of nurses that could be included in this definition and the benefits of broadening the category are discussed, as well as possible reasons for the less inclusive, previous definition of this category. Strategies are proposed for resolving concerns about broadening the category. PMID- 7870206 TI - The art of getting what you want. AB - Whatever your position in health care, persuading others is part of your role. For an administrator, convincing others is actually a common place occurrence throughout the workday and is not just reserved for major change. This article describes techniques in the art of persuasion including use of a triad, enthusiasm, specific examples, information, involving key staff, asking for a trial, discussing rather than writing, pointing out the advantages to the employee, and indicating that the idea is coming from administration. PMID- 7870207 TI - Purpose in life among gay men with HIV disease. AB - Positive purpose in life (PIL) has been shown to influence health maintenance, facilitate recovery from illness, and enhance psychological well-being. Among persons diagnosed with human immunodeficiency virus (HIV) disease, PIL has received minimal attention. This study used a convenience sample of 67 men who had a diagnosis of acquired immunodeficiency syndrome (AIDS) or who participated in high-risk sexual behavior associated with HIV disease to measure PIL. Integrating qualitative data into the final analysis contributed to a greater understanding of PIL among persons with HIV disease and those at high risk for the disease. Results of the study demonstrated a significantly lower PIL score for men with AIDS. PIL scores were negatively correlated with religious beliefs for the group, and these scores were not influenced by the interval since the AIDS diagnosis. Men with HIV disease are often isolated and withdrawn from society and appear to lack clear meaning for existence. PMID- 7870208 TI - The "any willing provider" provision and health system reform in Nebraska. PMID- 7870210 TI - Pharmacy cognitive services and mail order pharmacies. PMID- 7870209 TI - Are the germs winning? PMID- 7870211 TI - Three physician explorers. PMID- 7870212 TI - Hypersensitivity to therapeutic murine monoclonal antibodies. AB - OBJECTIVE: To determine the predictive value of pre-treatment skin tests and in vitro IgE/IgG4 anti-murine monoclonal antibodies in patients treated with murine monoclonal antibodies. DESIGN: Patients treated at two cancer institutions were evaluated by skin testing and solid phase immunoassays to detect IgE and IgG4 specific anti-murine monoclonal antibodies. Skin testing by scratch and intradermal skin testing was done on patients before treatment with murine monoclonal antibodies. IgE & IgG4 specific anti-murine monoclonal antibodies were determined before treatment in all patients and at 1, 7, 14 and 21 days post treatment in 1 patient. SETTING: Cancer patients undergoing murine monoclonal antibody treatment in two university medical centers were recruited for the study. PARTICIPANTS: Twelve patients, aged 41-75 years with gastrointestinal cancers (colon, stomach, pancreas or liver) with metastatic disease, who had relapses or conventional therapy were enrolled. Some patients had previous exposure to rodents, either as laboratory personnel or had kept them as pets. INTERVENTION: One patient who experienced an anaphylactic reaction to murine monoclonal antibody infusion was desensitized so therapy could continue. MAIN OUTCOME MEASURES: Skin tests, immunoassays, and patient history were correlated with adverse reactions to infusions of murine monoclonal antibodies. MAIN RESULTS: Skin tests (scratch method) and/or in vitro immunoassays may predict allergic outcomes in patients receiving infusions of murine monoclonal antibodies. Intradermal skin testing with murine monoclonal antibodies may result in false positive reactions and have less predictive value. Specific IgE or IgG4 were elevated in the two patients who experienced severe adverse reactions to murine monoclonal antibodies but not in those patients with no reactions and therefore, may have some predictive value. A history of past exposure to mice may also increase the risk of adverse reactions. In one patient, intravenous desensitization enabled treatment to proceed. CONCLUSION: Scratch skin tests, in vitro IgE and/or IgG4 immunoassays together with a past history of previous exposure to murine antigen(s) may predict potential allergic reaction to therapy with murine monoclonal antibodies. PMID- 7870213 TI - Flow cytometric determination of leukemia-associated marker combinations for the study of minimal residual disease. AB - To study the minimal residual disease in acute leukemia patients we used some marker combinations related either to the simultaneous surface membrane and cytoplasmic marker expression, or to the expression of atypical marker combinations, that are absent or extremely rare in normal hematopoietic cells. We investigated to which extent flow cytometric analysis of leukemia-associated marker combination may contribute to sensitive follow-up in patients with acute leukemia. For this purpose dilution experiments were performed, in which artificial mixtures of normal peripheral blood lymphocytes and leukemia cells from a patient with leukemia-associated phenotype were prepared and analyzed for double positive cells. Our results showed that the sensitivity of double color immunofluorescence assay was 3 in 10(4) cells. Sequential studies of residual disease were evaluated in five acute leukemia patients with leukemia-associated markers combinations at diagnosis. In three of them morphologic relapse was preceded by the immunologic detection of small amounts of leukemia cells, while in two other cases, in which no double positive cells for leukemia-associated markers were found, patients are still in hematologic remission. This approach to the study of minimal residual disease could be valuable in monitoring the efficiency of chemotherapy, as well as in evaluating the quality control of bone marrow before autografting. Furthermore, flow cytometric approach can efficiently complete other methods, which are used for more exact definition of remission in acute leukemia patients. PMID- 7870214 TI - Soluble interleukin-2 receptor in serum of patients with esophageal carcinoma. AB - We measured serum levels of sIL-2R in 28 patients with squamous cell esophageal carcinoma and in 12 controls. Sera for presence of sIL-2R were examined using DAKO Interleukin-2-receptor (CD25) ELISA. The samples were analyzed for CEA and SCC by using IMx System (Abbot). The mean values of sIL-2R in esophageal carcinoma group were significantly increased in comparison with control group. Our results suggest that sIL-2R may be useful in monitoring and prognosis estimation of disease in esophageal carcinoma and could be a valuable addition to the current spectrum of cancer markers. PMID- 7870215 TI - The value of bone marrow biopsy in the prognosis of hairy cell leukemia (HCL). AB - Histological findings in the bone marrow and their changes in the course of the disease and therapy were evaluated with respect to the prognosis in a group of 32 patients with hairy cell leukemia (HCL). Two types of bone marrow infiltration by hairy cells (HCs), the diffuse type and the interstitial type, respectively were found. The diffuse type of infiltration and the minimal or absent residual hematopoiesis (RH) at presentation were found with statistical significance to be unfavorable prognostic findings when compared with interstitial infiltration and persisting RH (p < 0.01). Reticulin fibrosis is a characteristic finding in HCL and was found in all but 2 patients. PMID- 7870216 TI - Correlation of cytosolic concentrations of ER, PS2, Cath-D, TPS, TK and cAMP in primary breast carcinomas. AB - In a group of 391 patients with primary breast cancer the cytosolic concentrations of ER, PS2, Cath-D, TPS, TK and cAMP were determined. PS2 production was found to be significantly dependent not only on ER but also on cAMP. A similar dependence on ER and cAMP production was found also in Cath-D. When the production of these prognostic factors was correlated with the occurrence of metastases to axillary lymph nodes, three prognostically unfavorable groups of primary breast carcinomas were revealed. The first group was represented by tumors with negative PS2 values (< or = 2.5 ng/mg) and elevated TPS values (> or = 4.0 kU/mg). The second group comprised prognostically very unfavorable tumors with moderately to highly elevated PS2 values and positive Cath-D values (> or = 35 pmol/mg), or positive TPS values (> or = 8.0 kU/mg). The third group was constituted by tumors with elevated TK (> or = 5.0 U/mg) and ER values (> or = 40 fmol/mg). The possible role of PS2 in the metastasizing of primary breast carcinomas is discussed. PMID- 7870217 TI - Lipoprotein profile in breast cancer women: effect of tamoxifen treatment. AB - Electrophoretic lipoprotein analyses were performed in 51 patients on tamoxifen and compared with those obtained from 33 newly diagnosed breast cancer patients and with data from the group of healthy women. A statistically significant lower rate of dyslipoproteinemia has been demonstrated in tamoxifen group in comparison with untreated patients; 23.5% vs. 54.5% (p < 0.01). Comparing the results of the latter group with normal subjects there was a significantly higher frequency of dyslipoproteinemia in untreated patients, 54.5% vs. 28.9% (p < 0.05). Our findings confirmed an estrogen-like influence of tamoxifen on lipoprotein profile in postmenopausal breast cancer patients. PMID- 7870218 TI - The contribution of ultrasonography to the differential diagnosis of breast cancer. AB - Overall consecutive breast abnormalities (259 carcinomas, 1820 benign) examined with breast ultrasonography (US) are reported. US sensitivity, specificity and positive predictive value were 67.6, 97.7 and 81.0%, resp. (the corresponding values were 57.9, 97.9 and 77.2% for palpation, 79.9, 93.5 and 73.7% for mammography, and 97.6, 92.6 and 87.6% for cytology). US sensitivity was unaffected by age, whereas it was strongly influenced by tumor size (pT1-76.1%; pT2-87.1%) and histologic type (intraductal-7.4%; invasive ductal/lobular-83.4%; invasive special types-64.1%). The features of the lesions at US were significantly associated with cancer (irregular margins, posterior acoustic shadowing) or benign lesions (anechoic structure, lateral shadowing, posterior acoustic enhancement) but had a limited diagnostic accuracy. Overall, US visualized 174 (benign-24, suspicious-150) of 188 palpable, and 32 (benign-7, suspicious-25) of 71 nonpalpable cancers. US contribution was determinant to final diagnosis in 4 of 7 cancers, missed at palpation and mammography, but was at least partially responsible for 8 unnecessary biopsies of benign lesions. A negative/benign US report contributed to avoid unnecessary biopsy in 71 suspicious cases at palpation/mammography. Routine US examination of clinical/mammographic abnormalities is recommended for the advantages of US guided aspiration and to reduce the frequency of unnecessary biopsies. PMID- 7870219 TI - The role of cisplatin in chemotherapy of advanced breast cancer. AB - Cisplatin containing regimens as first-line, second-line or as a third-line chemotherapy were administered in 26 and 36 patients, respectively. The overall response rate in patients on first-line chemotherapy was 53.9%, in patients on second or third-line chemotherapy 30.6%. The differences both in overall and disease-free survival between patients on first-line and on second/third-line chemotherapy were statistically significant in favor of women treated with first line chemotherapy (p = 0.05). Hematologic and nonhematologic toxicities were mild to moderate and were more pronounced in patients on second and third-line chemotherapy. The overall response rate, DFS and OS were significantly better and longer in the group of patients treated with "bolus" CDDP in comparison to the group of patients treated with CVI CDDP. Our results confirm the activity of cisplatin-containing regimens (mainly CAP schedules) in patients with advanced breast cancer not only as a first-line therapy but also in heavily pretreated patients by chemotherapy and/or radiation therapy and endocrine manipulation. PMID- 7870220 TI - Prognostic factors in bilateral breast cancer. AB - Twenty-nine bilateral breast carcinoma patients were analyzed retrospectively. The incidence of bilateral carcinoma of the breast among unilateral breast cancer patients was approximately 2.4%. Median age was 46 years at the time of first cancer diagnosis (range 26-69 years). The majority of the lesions were invasive ductal carcinoma (86%). Of 58 tumors, 10 were staged as Stage I (17%), 30 as Stage II (52%), 8 as Stage III (14%) and 10 as Stage IV (17%). Patients were treated with various combinations of surgery, radiation treatment and chemotherapy. Of 29 patients with bilateral breast cancer, 5 presented with simultaneous bilateral disease (17%), 7 (24%) with synchronous tumors whereas 17 (59%) developed asynchronous tumors. The mean interval between two cancers was 2.6 +/- 0.6 years. Overall survival was 4.8 +/- 0.7 years and overall 5-year actuarial survival was calculated to be 51%. Age, menopausal status and tumor size at the time of initial cancer correlated with the time interval between two cancers. Age, tumor size and nodal status at the time of initial cancer and the time interval between two cancers correlated with the overall survival. PMID- 7870221 TI - Non-IPSID small intestinal lymphoma: evidence for disseminated disease at presentation. AB - During the period 1984-1989 the authors have observed 20 patients with non-IPSID small intestinal lymphomas, 11 males and 9 females. In 11 patients the first symptoms were abdominal cramps requiring laparotomy, in 4 ileus, and in 5 perforation with peritonitis. Resection of the involved part of the intestine was performed in 17 patients. Lymphoma tissue was present in 4 of 5 retrogradely examined resection lines on macroscopically normal small intestine. According to Working Formulation, 3 patients had low grade, 3 intermediate grade and 14 high grade histology. Affection of extra intestinal/mesenteric structures was found in 18 of 20 patients, with a total of 36 other lymphoma localizations. 8 of 20 had affection of the nasopharynx and/or Waldeyer's ring. According to the Crowther's classification 55% of patients were in Stage IV, 35% in Stage III and 10% in Stage Ib. All patients were treated with chemotherapy, 13 with ProMACE regimen and 7 with CHOP-type regimens. Ten of twenty patients are alive and in complete remission for over 5 years (7 of 11 of Stage IV and 3 of 9 of Stage Ib/III; 8 of 14 with high grade and 2 of 6 with intermediate/low grade histology). Our results point to the fact that in non-IPSID lymphoma of the small intestine, lymphoma involvement of the intestinal wall might be present beyond obvious lymphoma lesions. Most patients with apparently primary small intestinal lymphoma have a widespread disease. Thus, local forms of treatment such as surgery, and/or radiotherapy can not be expected to be curative in the majority of patients. Data from this study suggest that following initial surgery the chemotherapy is the treatment of choice for these patients. PMID- 7870222 TI - Modulatory effect of Dalton's lymphoma cells on the production of reactive nitrogen intermediates, interleukin-1 and tumor necrosis factor by murine peritoneal macrophages. AB - The effect of Dalton's lymphoma (DL) cells on the production of reactive nitrogen intermediates (RNI), interleukin-1 (IL-1) and tumor necrosis factor (TNF) by murine peritoneal macrophages was investigated. Treatment of macrophages with LPS resulted in significant enhancement in the production of RNI, soluble and membrane-associated IL-1 and TNF. A significant inhibition in the production of RNI and IL-1 was observed when the macrophages were coincubated with DL cells whereas TNF production was enhanced. Incubation of macrophages in the presence of DL cells alone even in the absence of LPS could induce production of TNF level comparable to that of LPS-treated macrophages. Paraformaldehyde-fixed DL cells and DL cell conditioned medium could also inhibit RNI production by macrophages. On the other hand pre-exposure of macrophages to viable DL cells or DL cell conditioned medium prior to treatment with LPS could prime the macrophages for enhanced production of RNI. This study indicates that the regulatory effect of lymphoma cells on macrophage activation may have relevance of the host defence against tumors. PMID- 7870223 TI - Risk factors for thyroid cancer. AB - Case-control study comprised 100 histologically verified thyroid cancer patients (23 men, 77 women) and 100 hospital controls matched with cases by sex, age and place of residence. Various risk factors were studied to determine whether they were associated with the occurrence of thyroid cancer. According to the conditional logistic regression analysis, 6 were significantly related to the disease: Cigarette smoking (RR = 7.12 95% CI = 1.53-32.99), family history of any malignant tumors (RR = 5.84 95% CI = 1.76-19.44), history of goiter or thyroid nodules (RR = 27.69 95% CI = 3.11-246.14), long-term occupational exposure to chemicals (RR = 10.07 95% CI = 3.85-26.35), history of second primary tumors (RR = 15.49 95% CI = 3.46-69.30), and diagnostic X-rays exposure (RR = 7.56 95% CI = 2.85-20.07). PMID- 7870224 TI - Renal tubular cellular and molecular events in acute renal failure. PMID- 7870225 TI - Treatment of renal anaemia with recombinant human erythropoietin results in decreased red cell uptake of 45Ca. AB - The ability of erythrocytes to undergo deformation may be of importance to erythrocyte survival and to blood flow resistance. In a previous study a decreased deformability was demonstrated in the erythrocytes of uraemic patients treated with recombinant human erythropoietin (rhEPO). Erythrocyte deformability is, at least partly, determined by the intracellular concentration of free calcium ions. Six patients with renal anaemia (initial haemoglobin 95 +/- 11 g/l) were treated with rhEPO. They were examined with regard to certain erythrocyte characteristics before treatment and after reaching a haemoglobin concentration exceeding 120 g/l. A decrease was noted upon treatment in erythrocyte deformability and uptake of 45Ca in vitro. The blood pressure tended to increase. The individual values of the decrease in 45Ca uptake and the increase in systolic blood pressure were positively correlated to each other (r = 0.87; p < 0.05). No correlation was found between changes in erythrocyte deformability and 45Ca uptake. The decrease in 45Ca uptake may be interpreted in two different ways. It could reflect a reduced membrane permeability to calcium ions, or, which is more probable, it could be the end result of an increase in the intracellular metabolic pool of free calcium ions caused by the rhEPO treatment. We, therefore, conclude that rhEPO treatment has certain effects on calcium homeostasis in erythrocytes which may be related to blood pressure regulation. PMID- 7870226 TI - Delayed decrease in plasma levels of atrial natriuretic peptide during cold hemodialysis. AB - The high plasma levels of the vasodilating hormone atrial natriuretic peptide (alpha-ANP), observed in patients with chronic renal failure, decrease substantially during hemodialysis (HD), probably owing to volume reduction. Cardiovascular stability is better maintained by the use of cold dialysate although underlying mechanisms are unknown. In order to investigate the effects of different dialysate temperatures on hemodynamic stability and plasma levels of immunoreactive ANP (p-irANP), 10 stable HD patients were dialyzed with bicarbonate dialysis fluid for 240 min with each of 3 different dialysate temperatures: 36.5 degrees C (normal HD; NHD), 38.5 degrees C (warm HD; WHD) and 34.5 degrees C (cold HD; CHD). A Cuprophan plate dialyzer was used. The ultrafiltration volume and ultrafiltration rate were identical in each patient during the treatments. p-irANP was determined by radioimmunoassay, using 2 antisera which different cross-reactivity to ANP-related peptides. During NHD a nonsignificant decrease in mean arterial blood pressure from 111 +/- 5 to 103 +/- 8 mm Hg was observed. A significant (p < 0.05) decrease in mean arterial blood pressure from 109 +/- 4 to 96 +/- 6 mm Hg occurred during WHD, while during CHD it remained stable (111 +/- 4 before, 112 +/- 5 mm Hg after). Irrespective of the dialysate temperature or the antiserum used, p-irANP decreased significantly (p < 0.05) during the treatment. The reduction in p-irANP was delayed during CHD, the decrease being significantly (p < 0.05) less pronounced after 120 min. At the end of the treatment no significant difference was observed between the regimes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870227 TI - Increased incidence of HLA-B40 group antigens in children with hemolytic-uremic syndrome. AB - Hemolytic uremic syndrome (HUS) develops in 25-30% of children infected with Escherichia coli strains that produce Shiga-like toxins, also known as verocytotoxins. Mild HUS also occurs in 1 in 4 of the other family members, suggesting a familial predisposition to HUS. To understand the possible genetic predisposition, the frequency of HLA antigens was evaluated in 30 children (12 boys, 18 girls; mean age 3.8 years) with HUS following a prodrome of bloody diarrhea. When compared to a blood donor population from the same geographic area and ethnic background, no significant differences were noted in the frequency of HLA-A, HLA-C, HLA-DR, and HLA-DQ antigens. However, the frequency of HLA-B40 and its splits (B60, 61, 41, 47) was significantly higher in the study population (corrected p < 0.005). The relative risk of developing HUS was 6.04 when HLA-B40 and HLA-B40 split products were present, and the risk increased to 8.5 when the analysis was extended to include the cross-reactive antigens B44 and B13. These HLA-B antigens share common amino acid sequences at positions 41-45 and 67-74 on the alpha-1 domain of the HLA class I molecule. Our data suggest that the inheritance of HLA-B40, its splits, and cross-reactive antigens increases the risk of developing HUS. PMID- 7870228 TI - Gene expression and release of interleukin-8 by peritoneal macrophages and polymorphonuclear leukocytes during peritonitis in uremic patients on continuous ambulatory peritoneal dialysis. AB - Interleukin-8 (IL-8) has been reported to be released by activated peritoneal macrophages (PMs) and a variety of other cell types, and it exhibits potent chemotactic activity for polymorphonuclear cells (PMNs). We have previously shown that IL-8 is detectable in the drain dialysate of uremic patients on continuous ambulatory peritoneal dialysis (CAPD) during peritonitis. The levels of IL-8 in infected drain dialysate caused by different microorganisms were variable. In this study, we evaluated the gene expression and release of IL-8 by PMs and PMNs during peritonitis caused by Staphylococcus aureus in uremic patients on CAPD. IL 8 levels were variable in the drain dialysate at the different episodes of peritonitis, even in the same patient. The IL-8 levels were highly correlated with PMN count in drain dialysate (r = 0.9919, p < 0.001). PMs and PMNs obtained from drain dialysate at the onset of peritonitis increased mRNA expression for IL 8 and the amount of IL-8 mRNA from drainage cells was also highly correlated with PMN count. In contrast, cells isolated from drain dialysate without peritonitis failed to express mRNA for IL-8. These data suggest that increased expression of IL-8 may be a feature of peritonitis. The levels of IL-8 during peritonitis were not only related to the etiological microorganism but also to other unknown factor(s). PMID- 7870229 TI - Analysis of platelet abnormalities in uremia with and without Glanzmann's thrombasthenia. AB - Uremia causes a bleeding tendency associated with platelet dysfunction, and previous studies have shown abnormalities of platelet glycoprotein (GP) Ib or GPIIb/IIIa and a tendency for platelet activation in uremia. The present study compared the abnormalities of platelet function in uremia with (n = 1) or without (n = 18) associated Glanzmann's thrombasthenia. There was a significant difference between ristocetin-induced agglutination of platelets from the uremic patients without Glanzmann's thrombasthenia and platelets from healthy controls (n = 15). In addition, a reduction of GPIb expression by uremic platelets along with normal GPIIb/IIIa expression was confirmed using flow cytometry. Many coagulation markers were increased in the uremic patient with Glanzmann's thrombasthenia, suggesting that the coagulation was enhanced and the platelets were prone to activation. However, the thrombasthenic platelets actually showed little increase in the binding of a monoclonal anti-CD63 antibody directed against lysosomal integral membrane protein (which is expressed after platelet activation), while uremic platelets showed a marked increase. In addition, the expression of GPIb by thrombasthenic platelets was normal, while that of GPIIb/IIIa was markedly decreased. Our results suggest that thrombasthenic platelets are resistant to activation and to the degradation of GPIb under uremic condition and that this difference from 'ordinary' uremic platelets be related to the difference in GPIIb/IIIa. PMID- 7870230 TI - Glycosaminoglycans and oxalocalcic urolithiasis. AB - A very simple analytical procedure with dimethylmethylene blue as photometric reagent was applied for the evaluation of glycosaminoglycan (GAG) urinary excretions and concentrations in both sexes, calcium oxalate stone formers, and a control group. The GAG concentrations varied significantly in stone formers (males and females) and in the control group; moreover, in some individual cases, a deficit of urinary GAGs was clearly detected. Apart from important inhibitory effects of GAGs on heterogenous calcium oxalate nucleation, the low urinary GAG content could be the cause of a pathological epithelium, favoring stone formation. The dimethylmethylene blue method is recommended as a quick screening procedure to determine a GAG deficit. PMID- 7870233 TI - Allopurinol fails to protect against gentamicin-induced renal damage in normotensive and spontaneously hypertensive rats. AB - Recent research suggests the involvement of hydroxyl and superoxide free radicals in the development of gentamicin-induced acute renal tubular necrosis. Xanthine oxidase has been implicated as an important source of superoxide free radicals. Spontaneously hypertensive (Wistar-Kyoto) rats (SHR) have excessive oxidant stress which may render them more sensitive to the proported oxygen free radical producing effects of gentamicin. This study was undertaken to determine if the xanthine oxidase inhibitor allopurinol will ameliorate the effects of gentamicin. Normotensive Wistar-Kyoto (WKY) rats and SHR were administered allopurinol (40 mg/kg twice daily) orally 4 days before and throughout a 12-day gentamicin treatment period. The allopurinol only treatment group demonstrated no noticeable histological or functional changes considered to be indicative of nephrotoxicity. Gentamicin-injected WKY rats and SHR equally demonstrated extensive proximal tubular and glomerular damage characteristic of aminoglycoside-induced kidney damage. Allopurinol failed to protect either rat strain against the histological damage caused by gentamicin. Equivalent alterations in serum creatinine, serum gentamicin, urinary N-acetyl-beta-D-glucosaminidase excretion, body weight, urinary output, and blood pressure occurred in the gentamicin with allopurinol and gentamicin only treatment groups. Our results demonstrate allopurinol does not ameliorate the pathogenesis of gentamicin. SHR do not appear to be more sensitive to the effects of gentamicin induced kidney damage with or without allopurinol as compared with WKY rats. PMID- 7870232 TI - Progression of chronic renal failure in a rat strain with autosomal dominant polycystic kidney disease. AB - Recently, the existence of a rat strain exhibiting autosomal dominant polycystic kidney disease (PKD) resembling human PKD has been described. An exact description of the course of chronic renal failure in this strain, however, is still missing. Thus the aim of this study was to analyze the long-term course of renal failure in these rats. In addition, unilateral nephrectomy (UNX) was performed in order to evaluate the impact of UNX on the occurrence of uremia. Our data clearly revealed that 70-80% of all animals of this rat strain developed uremia within 21 months. Additionally, proteinuria and hypercholesterolemia occurred, while the blood pressure was fairly unaffected. Also a slight degree of anemia was noted. In this long-term study death was due to uremia. The median survival time was significantly shorter in UNX PKD (median 11.6 months) than in non-UNX PKD animals (17.0 months; log-rank test: p = 0.001). IN CONCLUSION: with respect to renal function this rat model resembles human PKD disease. Furthermore, we could demonstrate that UNX is suitable to accelerate the rate of progression of renal failure in this model. PMID- 7870231 TI - Toxic acute renal failure in the rat: effects of diltiazem and urodilatin on renal function. AB - Beneficial effects of natriuretic peptides have been reported in different models of acute renal failure (ARF). Calcium antagonists can also improve renal function, especially in ischemic models of ARF. The aim of our study was to investigate the effects of urodilatin and diltiazem alone and in combination in uranyl nitrate-induced toxic ARF in the rat. Three hours after induction of ARF glomerular filtration rate (GFR) was clearly diminished to about 50% compared to basal values. Intravenous infusion of diltiazem and urodilatin revealed a significant increase of GFR that even continued after cessation of drug delivery. Combined administration of urodilatin and diltiazem had no additional effect, probably due to a more pronounced fall in blood pressure in this group. Besides their vasorelaxing and blood pressure lowering effects both drugs also revealed diuretic activity. In conclusion both urodilatin and diltiazem are able to elevate GFR in the early phase of toxic ARF in the rat. PMID- 7870234 TI - Renal impairment and intraglomerular mononuclear phagocytes in cholesterol-fed rabbits. AB - Morphological and immunohistochemical studies using the anti-macrophage monoclonal antibody RbM2 were performed in cholesterol-fed rabbits. From the beginning of the experiment, the levels of lipoproteins showed the pattern of familial type III hyperlipoproteinemia patients, and glomerular endothelial and mesangial cells had lipid deposits. By the 3rd week, RbM2-positive cells appeared in the capillary lumina. These cells became larger and increased in number after the 8th week. Although they had become very large and had increased noticeably by the 20th week, few sclerotic glomeruli were observed. We could hardly detect any proliferation of or foamy changes in the mesangial cells, and monocyte/macrophages showed no proliferative capacity within the glomeruli. These findings suggest that hyperlipidemia alone did not cause proliferation or foam transformation of the mesangial cells. The glomerular macrophages, probably derived from circulating monocytes, did not induce a glomerular injury under the short-term hyperlipidemic conditions of these experiments. PMID- 7870235 TI - Recurrence of focal-segmental glomerulosclerosis in kidney transplant patients on ciclosporin. AB - Two patients on maintenance hemodialysis after terminal renal failure due to nephrotic syndrome and biopsy-proven focal-segmental glomerulosclerosis received three cadaver renal allografts. Immediate recurrence of nephrotic syndrome was observed. In two transplants immunosuppression consisted of ciclosporin A and low dose steroids. One patient was unsuccessfully treated with immunoadsorption after the second transplant. All grafts were lost because of uncontrolled nephrotic syndrome. Renal allograft biopsy specimens showed findings indicating recurrence of the original disease. PMID- 7870236 TI - Wegener's granulomatosis limited to the kidney as a masslike lesion. AB - We report on a 45-year-old female who presented with end-stage renal disease due to Wegener's granulomatosis limited to the kidneys. Ultrasonography and computed tomography revealed a masslike expansion involving the upper pole of an otherwise small right kidney. Histopathology of a nephrectomy specimen revealed cystic dilatation of renal tubules and active lesions of Wegener's granulomatosis in the upper pole. The lower part of the kidney showed atrophic changes. Wegener's granulomatosis presenting as a renal mass is extremely rare. Only 3 cases have been previously reported in the literature. Wegener's granulomatosis only limited to the kidney is also rare. A brief review of 23 previously reported cases who initially presented with renal disease is presented. All but 2 patients subsequently manifested extrarenal lesions. Our patient continues to be free of any extrarenal involvement 18 months following presentation, although subsequent development of extrarenal lesions cannot be ruled out. PMID- 7870237 TI - Comparison of three formulations of calcium acetate tablets to evaluate tolerance and control of hyperphosphatemia in patients with chronic renal failure. PMID- 7870238 TI - Nephrocalcinosis associated with primary aldosteronism. PMID- 7870239 TI - Bilateral renal stones associated with nail-patella syndrome. PMID- 7870240 TI - Immunological effects of recombinant human erythropoietin on end-stage renal disease pediatric and adult patients. PMID- 7870241 TI - Acute rhabdomyolysis and hemoglobin reduction after bezafibrate overdose in hyperlipidemic patients on hemodialysis. PMID- 7870242 TI - Susceptibility of Escherichia coli with capsular antigen K1 isolated from urinary tract infection on the joint action of cefotaxime and normal human serum. PMID- 7870243 TI - [Meningioma of the floor of the temporal fossa. Anatomo-clinical study of 11 cases]. AB - The authors present eleven cases of middle fossa floor meningiomas. They describe the anatomical and clinical features of these tumors in this rare localisation. They emphasize the strait anatomical relations with the cranial base, eight cases were inserted above the superior surface of the petrous bone, two above the endocranial face of the horizontal part of the greater sphenoid wing, one above the horizontal part of the temporal squama. Headache (6 cases) and memory loss (4 cases) are the most frequent clinical feature, seizures (2 cases) and neuropsychologic troubles were probably undervalued. Auditory signs were present in three cases. There was no visual defect and cranial nerve impairment. They insist on the necessity to obtain a complete preoperative temporal bone CT scan exploration. They think that a well advised surgical act is sufficient for these meningiomas inserted above weak structures and with good prognosis: there's no recurrence in this study with a follow up from 12 to 132 months. PMID- 7870244 TI - [Comparative study of disk surgery with or without microscopy. A prospective study of 80 cases]. AB - The authors report a randomized prospective study of 80 patients operated for lumbar disc herniation. In one group of patients, the operator used a microscopic discectomy, in the other group, the surgery was performed through an interlaminar approach without microscopic magnification. All patients were operated on by the same surgeon. The results have been evaluated by a blind neurosurgeon after 12 to 18 months. 90% patients of the two groups have an excellent or a good outcome following the criteria of Mac Nab. There is no difference, regarding the outcome, between microscopic and non-microscopic removal of disc herniation. Using the microscope does not influence the operating time, the post operative inpatient stay and the time off-work. The authors conclude that the use of the microscope, can facilitate the operation and give a better visual comfort, but does not improve the final results. PMID- 7870245 TI - [Malignant astrocytoma of the cerebellum. Apropos of 10 cases. Review of the literature]. AB - While reviewing a series of 138 cerebellar tumors operated upon between 1978 and 1991, the authors could only find 2 glioblastomas and 8 anaplastic astrocytomas, occurring in 4 children (3 to 14 years old) and 6 adults (23 to 48 years old). These 10 cases represent 2% of the all malignant gliomas population observed during the same period of time. Clinically speaking, nothing makes these tumors different from other cerebellar ones. However, with an heterogenous image and an irregular contrast enhancement, the CT (scan) appearance can lead to the diagnosis. 7 lesions develop within the cerebellar vermis (vermis cerebelli) and 3 develop within the cerebellar hemisphere. Total surgical resection is performed in 9 cases and subtotal resection in 1 case (because of the extension to the floor of the fourth ventricle). Adjunctive radiotherapy on their posterior cranial fossa is achieved in 8 cases. The 2 patients with a glioblastoma present with a recurrence of their tumor at 15 months and 6 years respectively, and eventually died. Out of the patients with an anaplastic astrocytoma, 4 are still alive without recurrence and with a median follow-up of 7 years. The pathogenesis of such lesions is discussed. An aggressive therapeutic management is suggested because of the possible prolonged survival rate. PMID- 7870246 TI - [Use of propofol in intracranial surgery in 83 consecutive patients]. AB - Propofol is an intravenous anesthetic agent with a short half-life allowing rapid recovery; it has cerebral hemodynamic effects similar to those of thiopental. The aim of the present study was to describe 83 patients (mean age 50.6 +/- 15.1 yrs) scheduled for intracranial surgery in whom a total intravenous anesthesia technique (TIVA) with propofol was used. 16 patients were operated in the sitting position. Mean propofol induction dose was 2.1 +/- 0.8 mg/kg combined with 2.3 +/ 1.8 micrograms/kg of fentanyl, 1.5 mg/kg of lidocaine, and 0.08 mg/kg of vecuronium to facilitate intubation. Before installation of the Mayfied pin-head holder, the site of the pins was infiltrated with 2-3 cc of lidocaine 1%. Anaesthesia was maintained with propofol 5.9 +/- 2.1 mg/kg/h and fentanyl 1.6 +/- 0.65 micrograms/kg/h. Mean values of mean arterial pressure and heart rate showed less than 10% variation at intubation, application of the pin-head holder and skin incision. Intracranial pressure measured by the lumbar route (after checking the patency of the CSF passage from the cerebral to the spinal compartments) varied by slightly more than 10%, starting at 11.3 +/- 6.0 mmHg before induction and 11.3 +/- 5.2 mmHg at intubation down to 9.5 +/- 4.5 mmHg after skin incision. The lumbar drainage in place allowed the surgeon to improve brain relaxation by drawing 5-20 cc of lumbar CSF. Duration of anaesthesia was 367 +/- 96 mn from induction to extubation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870247 TI - [Extracranial primary meningioma. Apropos of a case]. AB - The authors report a case of a primary extracranial meningioma at the vertex a rare localization which represents less than 2% of all meningiomas. Reviewing the literature they discuss pathogenesis, pathophysiology and histopathology of this lesion. PMID- 7870248 TI - [Cerebral metastases of testicular neoplasms. Apropos of 2 cases and review of the literature]. AB - The authors report two cases of brain metastasis of a testicular cancer in two young men. In the first case the histology was an embryonal carcinoma, in the second the association of a seminoma and a teratocarcinoma. The first patient was submitted to chemotherapy, neurosurgery and radiotherapy. The second one to chemotherapy alone. The survival time was respectively of 16 and 58 months. It looked interesting to review the different treatments and their indications in this extremely severe pathology to define the interest of surgery and radiotherapy, and the different prognostic factors. In the literature, among the various treatment, the role of chemotherapy is widely emphasized. The prognosis remains desperately bad when several brain metastasis exist, or if a brain metastasis develops during chemotherapy. PMID- 7870249 TI - [Pierre Janny (1921-1993)]. PMID- 7870250 TI - [Jean Lecuire (1912-1993)]. PMID- 7870251 TI - [Cranial asymmetries. Reflexions on plagiocephalies. Premature sutural synostosis or extracranial origin?]. AB - The authors relate a clinical and radiological (X Ray and TDM tridimensional) study with an anthropological (dry skulls) study of plagiocephaly. The aim is to find with the aid of a physical examination, some anatomic parameters which permit to differentiate cranial asymmetry with coronal premature synostotic suture from functional deformation with extracranial outset. The term plagiocephaly is used to define forehead asymmetry. It is necessary to study orbital rim, nasal root, malar eminence, ear and chin mid point position. The morphology of the skull is important to look: frontal flattering and also occipital flattering or bulging, contra-lateral frontal and pterional aera bulging. The authors conclude that a single parameter is necessary to differentiate the two kinds of plagiocephaly: the petrous bone position on the flattened frontal side: sagittalisation: fonctionnal plagiocephaly; frontalisation: synostotic plagiocephaly. PMID- 7870252 TI - [An unusual cervical tumor: meningioma. Apropos of a case of petrous origin. Review of the literature of meningioma presenting as cervical mass]. AB - Primary ectopic meningiomas are uncommon. The authors report a case of a 12-year old boy with a meningioma presenting as a neck mass. The conclusion of the initial biopsy was chemodectoma, but on surgical resection, the tumour was found to have invaded the petrous bone. Post-operative follow-up was uneventful but magnetic resonance imagery revealed extension to the cerebello-pontine angle, the cavernous sinus, the tentorium and the falx. The authors discuss the main pathogenic hypotheses and the classification of ectopic meningiomas. Based on 62 similar cases reported in the literature, primary ectopic meningiomas are found most often in young subjects, with no female predominance, neurofibromatosis is often observed and angioblastic or malignant features are frequent. These tumours can be divided into 6 localizations (jugulo-carotid space, lymph nodes, parotid gland, thyroid gland, soft paravertebral tissues, skin) and into 3 pathogenic groups (solitary ectopic tumour of the neck, tumour of the neck connected to a cranial or spinal meningioma, metastasis). Meningioma of the jugulo-carotid space with connection to the skull base is the most frequent entity. Solitary ectopic meningiomas of the neck occur in only 1 out of 5 cases. In 2 out of 3 cases, the neck localization involves a connection to a cranial or spinal meningioma. In a few cases the neck mass is a metastasis. These findings suggest that a complete neuroradiological work-up is required. Prognosis depends on the completeness of the surgical resection and the histologic aggressiveness frequently encountered. PMID- 7870253 TI - [Intramedullary spinal cord tumors. Report. French Society of Neurosurgery. 45th annual congress. Angers, June 12-15 1994]. AB - Since Guidetti and Slooff's masterbooks (1964), numerous papers have been devoted to intramedullary spinal cord tumors (IMT) and their treatment, most of them were focused on ependymomas and astrocytomas. Informed opinion was that these tumors were difficult to cure and that biopsy plus radiotherapy was the treatment of choice. Thanks to microsurgery and bipolar coagulation surgeons grew bolder and more efficient as illustrated by the contributions from Hurth or Resche on hemangioblastomas, Fischer on ependymomas, Epstein on childhood astrocytomas and Guidetti, Malis, Stein on IMT in general. Meanwhile, in the eighties, Magnetic Resonance Imaging (MRI) and Cavitron Ultrasonic Surgical Aspirator (CUSA) drastically modified diagnostic and therapeutic strategies of IMTs, as may be judged by the significant increase in the number of publications on this topic in current medical literature. However, no updated work of synthesis is currently available. This prompted us to publish our common experience based on 171 patients and 200 surgical procedures. Thanks to the collaboration of many colleagues of the "Societe de Neurochirurgie de Langue Francaise" (SNCLF) who completed a questionnaire sent to them, we are now in the position to give an epidemiological estimation based on 1117 cases. This work is divided in three main parts. The first part deals with considerations common to all IMTs, the second with particular aspects specific of each tumoral type, the third with the results and concluding recommendations. PMID- 7870254 TI - [Risk factors in subarachnoid hemorrhage]. AB - In 90 patients suffering from SAH and 260 controls certain clinical parameters were analysed to find risk factors in subarachnoid haemorrhage. In conclusion, it was statistically documented that among many known risk factors of arteriosclerosis only hypertension and heavy smoking considerably increased the risk of SAH in the analysed group of patients. PMID- 7870255 TI - [Diagnostic value of oligoclonal band detection in cerebrospinal fluid using PhastSystem device]. AB - The study confirming the presence of oligoclonal IgG in cerebrospinal fluid by isoelectric focusing (IEF) with PhastSystem equipment was carried out in 68 patients with clinically definite MS, in 23 with clinically probable MS and in 23 with other neurological diseases. Other indicators intrathecal synthesis of IgG were olso marked. According to the results it was confirmed that the most sensitive method of detection of intrathecal synthesis of immunoglobulins is finding of the oligoclonal IgG. Using the PhastSystem evidently shorties the diagnostic process. The sensivity of the method equals that of MRI and both have similar clinical value. PMID- 7870256 TI - [Clinical electroencephalographic diagnosis of myoclonus in various types of epilepsy]. AB - Twenty-six epileptics, 16 males and 10 females, with various types of myoclonia were studied. In all patients routine EEG, 24-hour EEG and/or Video-EEG, also with EMG recording were done. Combined detailed clinical-electrophysiological analysis was possible owing to the modern methods of diagnostic examinations and it enabled five epileptic syndromes to be isolated in this group, that is: childhood epilepsy with absence attacks (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), progressive myoclonic epilepsy (PME) and photogenic epilepsy. Clinical features of four types of myoclonia occurring in these cases are described in detail since they make possible differential diagnosis of epilepsy syndromes. This is important since the diagnostic and therapeutic methods differ in these cases, and similarly the prognosis varies in these epilepsy types. Stress is laid on juvenile myoclonic epilepsy which is as yet too rarely or erroneously diagnosed. PMID- 7870258 TI - [The effect of hyperlipidemia on pharmacokinetics of free phenytoin]. AB - The problem of the effects of metabolic changes on drug pharmacokinetics is not yet sufficiently known. Phenytoin was used for the assessment of the effects of lipid profile disturbances on drug pharmacokinetics. Phenytoin is a lipophilic substance. It was shown that hyperlipidaemia changed phenytoin pharmacokinetics and the pattern of these changes depended on the type of hyperlipidaemia. In hypercholesterolaemia and in mixed hyperlipidaemia the level of free phenytoin was raised in the blood. It should be remembered that hypercholesterolaemia and mixed hyperlipidaemia are conditions increasing the risk of phenytoin overdosage and this should be considered in establishing drug dosage. PMID- 7870257 TI - [T3, T4 and TSH serum levels in patients on long-term treatment for epilepsy]. AB - The serum T3, T4 and TSH concentrations were assessed by RIA method in 25 (14 females, 11 males) long-term treated (mean treatment duration 12.8 years) epileptic patients. The mean serum T3, T4 and TSH levels were lower than in control group according to clinical picture of epilepsy and treatment applied. The lowest mean serum TSH concentration was in patients with known aetiology of epilepsy. Patients with tonic-clonic seizures had lower serum levels of all hormones measured in comparison with the patients with partial seizures. Mean serum T3, T4 and TSH levels were low in patient group receiving valproic acid. The lowest mean TSH serum concentration as compared to control group was in the patients treated with phenytoin. None of the epileptic patients developed clinical symptoms of hypothyreoidism. PMID- 7870259 TI - [Surgical treatment of epilepsy: current status and results of own observations]. AB - New diagnostic possibilities make possible a more precise localization of epileptogenetic foci and surgical treatment of epilepsy is associated presently with minimal risk. This was the reason of a surge of interest in recent years even in those countries where this method has not been used. In our country operations for chronic refractory epilepsy have been performed since over 35 years and the gathered experience is sufficient to reach conclusions about the results. The results depend in a certain degree on the location of the focus and the surgical possibility of its removal. In about 50% of the cases cure was effected, and in 15% improvement was achieved near cure. Considering that the treated patients had long-standing and refractory epilepsy with very frequent seizures the results of surgical removal of epileptogenic focus were very good. The authors believe that patients with chronic, focal and refractory epilepsy should be treated surgically, and conservative treatment without considering this possibility is erroneous. PMID- 7870260 TI - [Cerebral blood changes during neuropsychological tests administered by Doppler sonography. Preliminary report]. AB - The preliminary studies on cerebral blood flow changes during neuropsychologic tests were carried out using transcranial Doppler sonography (TCD). The procedure with the standardized cerebral activation in order to obtain the control brain activity level was elaborated and tested. Blood flow velocity changes were measured during two groups of tests: linguistic with left dominant hemisphere and visual-spatial with right dominant hemisphere. Similar dynamics of blood flow changes was observed with all kinds of brain activation with the maximum velocity increase of 15-20%. The velocity measured in the dominant hemisphere was about 8 10% above the contralateral side. TCD seems to be complementary to the neuropsychologic tests useful especially in diagnosis of different types of dementia. PMID- 7870261 TI - [Vascular regions of the spinal cord]. AB - In a material of 50 spinal cord specimens obtained from adults the radicular anastomotic arteries were studied. After an analysis of the situation, diameter and connections of these arteries seven vascular regions were discerned in the cord: upper cervical region C1-C3, middle cervical region C4-C5, cervical intumescence region C6-C8, upper thoracic region Th1-Th3, middle thoracic region Th4-Th7, thoracolumbar intumescence region Th8-L4, and lumbosacral region L5-Co. Arterial systems found in these regions are described. PMID- 7870262 TI - [Visual evoked potentials in clinical diagnostics]. PMID- 7870263 TI - [Clinical assessment of the severity of craniocerebral injury]. AB - Assessment of overall patient responsiveness (coma grading) is essential in the characterization of craniocerebral injuries and grading of their severity. The combination of psychological and anatomical scores and additional examinations has yielded patient characterization which more accurately relates to outcome than when those scores are used alone. The aim of this study was to survey the methods of craniocerebral injury evaluation in neurosurgical practice. PMID- 7870264 TI - [Vasoactive neuropeptides CGRP (calcitonin gene-related peptide) and vasospasm during subarachnoid hemorrhage from ruptured intracranial aneurysm]. AB - The authors discuss the role of active neuropeptides Calcitonin Gene-Related Peptide (CGRP) and Vasoactive Intestinal Polypeptide (VIP) in the arterial spasm caused by haemorrhage from ruptured intracranial aneurysm. These substances act as vasodilators on brain vessels. Between the first and the second week after subarachnoid haemorrhage their concentration in the periarterial nerve fibres of the big vessels is significantly low. According to the experiments, the erythrocytes are this component of the blood which causes the decrease of the number of nerve fibres containing CGRP and VIP. The clinical tests of CGRP and VIP in the treatment of the vascular spasm after subarachnoid haemorrhage are being continued. PMID- 7870265 TI - [The image of intracerebral calcification in CT and MR studies. A case report of Fahr syndrome]. AB - A case of symmetric "calcifications" in the white matter of cerebral hemispheres, basal ganglia and cerebellum is reported in a patient without parathyroid function changes and calcium-phosphorus metabolism disturbances (Fahr syndrome). Attention is called to differences in the extensiveness of these deposits in CT and MRI examinations. The cause of false magnification of the outline of calcifications in CT images is discussed. PMID- 7870266 TI - [Chronic inflammatory demyelinating polyradiculoneuropathy]. AB - The authors presented the case of a 32-year-old male patient with a 22-year history of chronic inflammatory demyelinating polyradiculoneuropathy. They paid attention to the number of recurrences and the effects of corticosteroid therapy. They also emphasized that only the peripheral nervous system was affected. PMID- 7870268 TI - [Aneurysm of the anterior communicating artery as a possible late complication of internal carotid artery ligation]. AB - A case of a 55-year-old woman with anterior communicating artery aneurysm has been described. The aneurysm led to subarachnoid haemorrhage 8 years after ligation of the right internal carotid artery in order to turn off an aneurysm of this artery. Angiography showed the existence of collateral circulation through the arterial circle of the brain with haemodynamic disturbances, confirmed by Doppler ultrasonography. According to the views found in the literature these disturbances are considered the probable factor of initiation of the described aneurysm. PMID- 7870267 TI - [Two cases of Fisher syndrome with histopathological examination]. PMID- 7870269 TI - [A case of intrasellar teratoma]. AB - The authors present a case of teratoma adultum of unusual intrasellar localisation. The tumour was surgically treated with excellent result. It was confined to sella turcica and partially invaded the suprasellar region. It produced headache, mild bitemporal hemianopsia and did not cause clinically evident hormonal disturbances. PMID- 7870270 TI - [On the issue of intravenous administration of nimodipine in patients with ischemic stroke]. PMID- 7870271 TI - A theory of cooperativity modulation in neural networks as an important parameter of CNS catecholamine function and induction of psychopathology. AB - Recent research in computational neuroscience has suggested that psychosis associated with disturbed catecholamine neurotransmission may result from disturbances in the gain parameters of neural networks that these same secondary neurotransmitters are thought to control. We propose a mathematical model based upon cooperativity theory used in thermodynamics to explain how the gain parameter that momentarily increases the effect upon the post-synaptic cell of a given weighted connection from the presynaptic cell could be instantiated in the fluctuating electrical conductance of the dendrite of a neuron without requiring extensive ion transport or utilization of the ATP energy cycle. More specifically we propose that catecholamine neurotransmission serves to maintain the dendrite in a cooperative state with regard to changes in electrical conductance due to impulse traffic alone. In this way we supply the neuron with an activity driven gain parameter that not only increases volume of neuronal output at very low energy cost but that also upscales cooperative effects at the mechanico-chemical level of the dendrite to the network level itself. An important implication of this model is that two extreme states for dendritic electrical conductance will occur if cooperativity is lost at the level of catecholamine depletion or excess due to drug effects. These are the AND gate effect in which dendritic conductance is so low that the neuron requires extensive synaptic activity in order to output significantly. We correlate this state with negative symptoms in schizophrenia and psychomotor retardation in depression as well as the rigidity in Parkinsonism. The other extreme is represented by the OR gated dendrite in which conductance is so high that even noisy input to the dendrite will lead to significant nerve cell output. We correlate this condition with the positive symptoms of schizophrenia, the agitated features of psychotic depression and the tremors of Parkinsonism. PMID- 7870272 TI - Decrease in cerebellar blood flow in patients with Friedreich's ataxia: A TC HMPAO SPECT study of three cases. AB - Three cases of Friedreich's ataxia were submitted to diverse neuroradiological procedures in order to determine the extent of atrophic processes in the central nervous system. All patients underwent computerized-tomography scan, Magnetic Resonance Imaging, and HMPA-single Photon emission computerized tomography studies, focusing in cerebellar lobes. A slight atrophy was observed in the vermis and the cerebellar lobes with CT scan and MRI. In contrast a significant decrease in cerebellar blood flow was shown by TC-HMPAE SPECT study. The significance of these findings in understanding physiopathological mechanisms in Friedreich's ataxia is discussed. PMID- 7870273 TI - A computer simulation of the haemodynamic effects of intracranial arteriovenous malformation occlusion. AB - To study the effect of AVM occlusion on cerebrovascular haemodynamics, a simplified model was simulated consisting of a feeding artery supplying a capillary bed in parallel with a fistula-like malformation, both emptying into a draining vein. An electrical circuit analogue of the physiologic system was developed using lumped proximal and distal pressure dependent resistances, and capacitors representing vascular compliance. Autoregulation was introduced as a pressure varying precapillary arteriolar resistance. Equations derived from the circuit model were simulated using a graphical modeling program. The model successfully simulates phenomena angiographically observed during embolization procedures. Fistula pressure is shown to rapidly fall following proximal AVM occlusion, in contrast to a marked rise seen with distal occlusion, which is associated with biphasic flow into and out of the fistula and the arterial feeder. The model predicts an increase in capillary pressure and capillary flow which, depending on the magnitude of the flow increase and the state of autoregulation, may result either in reversal of ischaemia or hyperperfusion injury. Vascular overload is predicted in the absence of autoregulation. There is, however, little potential for vascular overload when autoregulation is intact. The model represents a first step in the mathematical characterization of the phenomenon of hyperperfusion following AVM occlusion. PMID- 7870274 TI - Dynamical chaos determines the variability of transcranial Doppler signals. AB - In order to estimate whether or not the variability of a timeseries of transcranial Doppler (TCD) waveforms is the result of a random or a deterministic process the following study was designed. From eight normal volunteers the middle cerebral artery blood flow velocities were measured for 50 sec and the maximum blood flow velocities (or waveforms) were analysed. From these waveforms socalled attractors were reconstructed and shown in a two dimensional phase portrait. The attractor of the TCD timeseries shows the entire range of states the cardiovascular system can display. The geometric structure of the attractor can be estimated by calculation of the correlation dimension D2. The correlation dimension D2 shows that the time evolution of the TCD timeseries is essentially nonperiodic and can be characterized by low dimensional chaos. It has been shown that the D2 value during hypocapnia has a significant higher value compared to the D2 values during normocapnia. The biological and clinical significance of these observations are outlined. PMID- 7870275 TI - The effects of naloxone on the post-asphyxic cerebral pathophysiology of newborn lambs. AB - Both early post-ischaemic blood-brain barrier disruption and enhanced brain endogenous opioid system activity have been implicated in the pathogeneses of ischaemic neuronal damage; however, their roles in neonatal asphyxia have not been evaluated. Under alpha-Chloralose anaesthesia, 17 newborn lambs were asphyxiated until their mean arterial pressures were < or = 25 mmHg. They were then immediately resuscitated, and assigned to two groups. Group I, but not group II lambs received IV bolus of 10 mg kg-1 Naloxone within 5 min of resuscitation. The infusion was continued at the same dose hourly until sacrificed 24 h post asphyxia. Arterial pH/gases, intracranial/arterial pressures, and rectal temperature were monitored. Neurological examinations were performed on both groups prior to sacrifice, and the blood-brain barrier integrity was assessed by Evans blue. Despite aggressive resuscitation, 5 lambs died during asphyxia, but 12 survived and were assigned according to the protocol. There were no significant group differences in the magnitude of asphyxia, arterial and intracranial pressures. However, blood-brain barrier disruption was observed in 5 out of 6 untreated, and in only 1 of the 6 lambs treated with Naloxone (p < 0.05). Severe neurological abnormalities were observed in 75% of lambs with disrupted, but in none of the animals with intact blood-brain barrier (p < 0.05). Our study suggests that post-asphyxia blood-brain barrier disruption is causally related to poor neurological outcome, and that Naloxone prevents both the disruption, and the neurological dysfunction among those survivors with intact blood-brain barrier. PMID- 7870277 TI - A nonlinear mathematical model for the development and rupture of intracranial saccular aneurysms. AB - Mathematical models of aneurysms are typically based on Laplace's law which defines a linear relation between the circumferential tension and the radius. However, since the aneurysm wall is viscoelastic, a nonlinear model was developed to characterize the development and rupture of intracranial spherical aneurysms within an arterial bifurcation and describes the aneurysm in terms of biophysical and geometric variables at static equilibrium. A comparison is made between mathematical models of a spherical aneurysm based on linear and nonlinear forms of Laplace's law. The first form is the standard Laplace's law which states that a linear relation exists between the circumferential tension, T, and the radius, R, of the aneurysm given by T = PR/2t where P is the systolic pressure. The second is a 'modified' Laplace's law which describes a nonlinear power relation between the tension and the radius defined by T = ARP/2At where A is the elastic modulus for collagen and t is the wall thickness. Differential expressions of these two relations were used to describe the critical radius or the radius prior to aneurysm rupture. Using the standard Laplace's law, the critical radius was derived to be Rc = 2Et/P where E is the elastic modulus of the aneurysm. The critical radius from the modified Laplace's law was R = [2Et/P]2At/P. Substituting typical values of E = 1.0 MPa, t = 40 microns, P = 150 mmHg, and A = 2.8 MPa, the critical radius is 4.0 mm using the standard Laplace's law and 4.8 mm for the modified Laplace's law.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870276 TI - Immunofluorescence and biochemical studies of the type VI collagen expression by human glioblastoma cells in vitro. AB - The human glioblastoma cell line U-87 MG was found to express a 140 kD polypeptide which was recognized on immunoblot analysis by a monoclonal antibody to type VI collagen. This polypeptide was digestible by a highly purified bacterial collagenase. After treatment of U-87 MG cells by pepsin, the protein profile revealed the two major pepsin-resistant fragments identical in Mr to those of collagen VI extracted from human placenta. The respective peptide maps from V8 protease one-dimensional gels of these two fragments were identical to those obtained with human collagen VI. Immunofluorescent staining by antibodies to type VI collagen was observed in the extracellular matrix. Moreover, U-87 MG cells were found to be positive for A2B5, a cell surface marker specific for O-2A type glial precursor cells. These data indicate that the human glioblastoma cell line U-87 MG exhibits the properties of glial precursor cells and expresses collagen type VI in vitro. This cell line therefore may prove valuable for comparative investigations of the regulation of type VI collagen synthesis, and may be useful as a model to study the function and pathological importance of type VI collagen in human brain tumours, both in vitro and in vivo. PMID- 7870278 TI - Lymphocyte subsets in relapsing-remitting multiple sclerosis: a longitudinal study of B lymphocytes and T lymphocytes. AB - Changes in lymphocyte subset populations may provide clues to the dysimmune mechanisms involved in relapsing remitting multiple sclerosis (RRMS). The lymphocyte subgroup CD4+ CD45RA+, thought to be responsible for the induction of suppression is decreased in some patients with MS compared to controls. A possible role for another lymphocyte subset, CD19+CD5+ lymphocytes, has been proposed in autoimmune diseases and multiple sclerosis (MS). To expand this we studied CD4+CD45RA+ (T) lymphocytes and CD19+CD5+ (B) lymphocytes in nine patients with relapsing-remitting MS (RRMS) and nine controls. The patients were examined monthly for an average of ten months and nine relapses were observed in seven patients. One patient underwent monthly gadolinium enhanced magnetic resonance imaging (MRI). Normal percentages CD4+CD45RA+ lymphocytes were found in patients with RRMS. No significant abnormalities in the CD19+CD5+ lymphocyte subpopulation were noted, although a tendency for higher percentages of this subset (approaching statistical significance, P = 0.056) was detected. PMID- 7870279 TI - Recordings from the facial motonucleus in rats with signs of hemifacial spasm. AB - We recorded evoked potentials from the facial motonucleus of rats in response to electrical stimulation of the temporal branch of the facial nerve in which chronic irritation from a blood vessel had caused the development of an abnormal muscle response. The abnormal muscle response that can be recorded from face muscles that are innervated by one branch of the facial nerve in response to electrical stimulation of a different branch is regarded to be a sign of hemifacial spasm. In the recordings from the motonucleus in rats that showed such an abnormal muscle response (model rats) there was a late component at a latency of about 5 msec, in addition to the early component with a latency of 1.5-2.5 msec that is also observed in normal rats. The latency of the electromyographic potentials recorded from the mentalis-orbicularis oris muscles in response to stimulation of the facial motonucleus was about 2 msec. The latency of the abnormal muscle response obtained from the mentalis muscle in the model rats was about 7 msec. This value is close to the sum of the conduction time from the motonucleus to the mentalis muscle (2 msec) and the latency of the late response from the motonucleus (5 msec). Similar results were obtained in rats in which the facial nerve had been chronically stimulated electrically and which had developed an abnormal muscle response. The results of this study further support the hypothesis that the hyperactivity of the facial motonucleus is the pathophysiology of hemifacial spasm. PMID- 7870280 TI - Selective and prolonged MRI enhancement by Mn-TPPS in an experimental rat brain tumour with peripheral benzodiazepine receptors. AB - Synthesized Mn-TPPS, a paramagnetic metalloporphyrin, is expected to be a tumour specific contrast media for magnetic resonance (MR) imaging. We investigated the enhancing characteristics of Mn-TPPS using a transplanted rat C6 glioma model with peripheral type benzodiazepine (PBD) receptors since porphyrins are thought to possibly be endogenous ligands for PBD receptors. An Mn-TPPS enhancement study was then performed either with or without pretreatment while using peripheral and central type benzodiazepine receptor specific ligands (PK11195 and clonazepam, respectively). A signal intensity analysis disclosed the selective and prolonged enhancement of the brain tumour even at 17 h after the Mn-TPPS injection. This specific enhancement of the tumour, however, was not inhibited nor replaced by benzodiazepines. The tissue concentration of Mn-TPPS was significantly higher in the glioma tissue than the other tissues, while PK11195 pretreatment could not reduce the intratumoural Mn-TPPS concentration. A subcellular distribution study disclosed that Mn-TPPS was readily incorporated into the tumour cells. On the other hand, Mn-TPPS was not specifically distributed in the mitochondrial fraction where PBD receptors exist. The present study therefore indicates that Mn TPPS could be incorporated into tumour cells and supports the potential use of this agent to improve the diagnostic specificity of MR imaging for brain tumours. PMID- 7870281 TI - Predictability of intracranial pressure oscillations in patients with suspected normal pressure hydrocephalus by transcranial Doppler ultrasound. AB - Intracranial pressure (ICP) was monitored continuously for one night in 36 patients with suspected symptomatic normal pressure hydrocephalus (NPH) to identify patients who might benefit from subsequent shunting. In 33 of these patients middle cerebral artery (MCA) blood flow velocity by means of transcranial Doppler sonography (TCD) and ICP were recorded simultaneously. ICP B waves always paralleled changes in the TCD signal (TCD B-wave equivalents). The relative frequency of ICP B-waves was predictable by TCD, albeit slightly underestimated due to a generally lower relative amplitude of the TCD B-wave equivalents. However, the same TCD B-wave equivalent amplitude could be accompanied by quite different ICP changes in different patients. Considering the baseline values in the absence of pressure waves, there was no significant relationship between ICP and TCD resistance index (Pourcelot) in different patients. Raising ICP by injection of 10 ml saline into the ventricle, however was accompanied by an increased TCD resistance index in the individual patient. As the relative frequency of B-wave activity is assumed to be an indicator for shunt responsiveness, continuous TCD monitoring can be used as a screening procedure to detect the presence and the relative frequency of B-wave activity in patients with suspected NPH. However, since neither the absolute ICP nor the amplitude of spontaneous oscillations can be predicted, TCD monitoring is not suitable to replace ICP monitoring. PMID- 7870282 TI - Case report: choriocarcinoma presenting with brain metastases. AB - Although choriocarcinoma is a gynaecologic malignancy, it may well present with nongynaecologic symptoms. We present such a case with metastases to the lungs and brain. The malignancy had arisen in a full-term pregnancy ending nine months prior to admission. In female patients presenting with cerebral metastases, a pregnancy test will either confirm or dismiss the possibility of choriocarcinoma. PMID- 7870283 TI - Actions of redox-related congeners of nitric oxide at the NMDA receptor. AB - The local redox milieu of a biological system is of critical importance in understanding the actions of the nitrogen monoxide (NO) moiety, as disparate chemical pathways involving distinct redox-related congeners of NO may trigger neurotoxic or neuroprotective pathways. The reactions of nitric oxide (NO.) with superoxide can lead to neurotoxicity through formation of peroxynitrite, whereas NO. alone does not, at least under certain conditions. Reaction (or transfer) of NO+ equivalents to thiol(s) on the NMDA receptor can lead to neuroprotection by inhibiting Ca2+ influx. These findings suggest that cell function can be controlled by, or through, protein S-nitrosylation, and raise the possibility that the NO group may initiate signal transduction in or at the plasma membrane. Neuroprotective effects of NO- suggest that acceleration of disulfide bond formation at the NMDA receptor is of mechanistic importance in the attenuation of Ca2+ influx. Our findings suggest novel therapeutic strategies. For example, downregulation of NMDA receptor activity can be obtained via sulfhydryl oxidation by S-nitros(yl)ation with NO+ donors (to form an RSNO at a cysteine residue on the receptor), or with NO- donors (with intermediate formation of RSNHOH). Pharmacologic intervention with these forms of NO donors could be implemented in the treatment of focal ischemia, neuropathic pain, Huntington's disease, AIDS dementia, and other neurological disorders associated, at least in part, with excessive activation of NMDA receptors. PMID- 7870284 TI - Models of the diffusional spread of nitric oxide: implications for neural nitric oxide signalling and its pharmacological properties. AB - Nitric oxide (NO) functions as a diffusible messenger molecule in many different tissues, including the brain. To create a conceptual framework for understanding the behaviour of NO in a biological (particularly neurobiological) scenario, we have developed theoretical models describing the kinetic and concentration profiles for NO generated from single or multiple sources. It is predicted that the physiological sphere of influence of a single point source of NO that emits for 1-10 sec has a diameter of about 200 microns corresponding to a volume of brain enclosing 2 million synapses. Inactivation of NO (imposed as a half-life of 0.5-5 sec) has only relatively minor effects because diffusion is so fast. When there are multiple simultaneously-active NO sources within a tissue volume, and in the absence of decay of NO or of a time-dependent reduction in source strength, the concentration of NO simply rises linearly with time, indicating the likely importance of negative feedback by NO on NO synthesis. Distant sources (200-500 microns away) make significant contributions to the steady-state NO concentrations in this situation even when the half-life of NO is short (0.5-5 sec). The models predict the results of several pharmacological experiments that were interpreted to suggest that a NO-containing molecule, rather than NO itself, is the endogenous messenger. Accordingly, invoking the presence of a hypothetical "NO carrier" on the basis of these experimental results is unnecessary. PMID- 7870285 TI - Modification of cysteine residues within G(o) and other neuronal proteins by exposure to nitric oxide. AB - Nitric oxide (NO), a free-radical gas produced endogenously by some neurons, functions as a diffusible intercellular messenger and appears to play a role in activity-dependent modification of synaptic efficacy in the mammalian CNS. The molecular targets and mechanisms of action of NO in neurons remain largely uncharacterized. Employing in vitro brain slices and isolated synaptosomes, we show here that exposure to exogenous or endogenously generated NO results in the modification of cysteine residues within neuronal proteins, as revealed by reduced binding of agents which react with cysteine sulfhydryls. In particular, exposure of synaptosomes to NO inhibits subsequent thiol-linked ADP-ribosylation of the heterotrimeric G-protein, G(o), by pertussis toxin. Our results demonstrate directly that NO may exert its neuronal effects through modification of protein cysteine thiols, and identify G(o) as a potential synaptic target of NO. PMID- 7870286 TI - NANC neurotransmission in the bovine retractor penis muscle is blocked by superoxide anion following inhibition of superoxide dismutase with diethyldithiocarbamate. AB - This study examined the effects of inhibiting Cu/Zn superoxide dismutase with diethyldithiocarbamate (DETCA) on the ability of superoxide generating agents such as pyrogallol, hypoxanthine/xanthine oxidase and LY 83583, to influence NANC relaxation of strips of bovine retractor penis (BRP) muscle. Although pyrogallol (100 microM) and hypoxanthine (0.3 mM)/xanthine oxidase (64 mU ml-1) had little effect on NANC relaxation in control strips, both induced almost complete inhibition following treatment with DETCA (3 mM) for 1 h. Inhibition was due to the actions of superoxide anion since it was blocked by the addition of exogenous superoxide dismutase (250 U ml-1). LY 83583 (0.1-30 microM) produced a concentration-dependent inhibition of NANC relaxation even in control strips and this too was blocked by exogenous superoxide dismutase, but sensitivity to inhibition was enhanced 10-fold following treatment with DETCA. The data suggest that under normal circumstances the NANC neurotransmitter is protected by high levels of tissue superoxide dismutase, and inhibition of this enzyme increases its susceptibility to destruction by superoxide anions. An important impediment to accepting free nitric oxide as the NANC neurotransmitter in the BRP on the basis that superoxide anion-generating agents inhibit the actions of authentic nitric oxide but not those of NANC nerve stimulation has thus been removed. PMID- 7870287 TI - Relationship between nitric oxide and vasoactive intestinal polypeptide in enteric inhibitory neurotransmission. AB - Although considerable evidence suggests that NO serves as a neurotransmitter in gastrointestinal muscles, it is unlikely to be the only substance involved in enteric inhibitory neurotransmission. Vasoactive intestinal polypeptide (VIP) is known to be expressed by inhibitory motor neurons in the gut, and it appears to be co-localized with nitric oxide synthase (NOS) in a subpopulation of enteric neurons. These data suggest that NO and VIP may be parallel neurotransmitters. Others have suggested that VIP is the primary inhibitory transmitter, and it stimulates production of NO in smooth muscle cells. In this "serial cascade" model NO is a paracrine substance. We performed experiments on circular muscles and cells from the canine proximal colon to further test the idea that NO and VIP are parallel neurotransmitters and to determine the validity of the serial cascade model in these muscles. We found that NO-independent inhibitory effects were unmasked when excitatory and NO-dependent inhibitory responses were blocked. NO-independent inhibitory effects were reduced by alpha-chymotrypsin and blocked by tetrodotoxin. NOS- and VIP-like immunoreactivities were co-localized in enteric neurons and varicose fibers in the circular muscle layer. Similar to several other reports we found no evidence for a constitutive NOS in smooth muscle cells. Several aspects of the serial cascade model were not supported by our results: (i) the electrical and mechanical effects of VIP did not depend upon NO synthesis; (ii) VIP-induced changes in [Ca2+]i did not depend upon NO synthesis; and (iii) VIP did not cause the release of NO from canine colonic muscles. These results are consistent with the hypothesis that NO and VIP are co transmitters, released in parallel from enteric inhibitory nerves. PMID- 7870288 TI - Effect of aminoguanidine on the impaired nitric oxide-mediated neurotransmission in anococcygeus muscle from diabetic rats. AB - The contribution of advanced glycation end-product (AGE) formation to alterations in nitrergic neurotransmission caused by 8-week streptozotocin-induced diabetes has been examined in the rat anococcygeus muscle. Relaxant responses to nitrergic nerve stimulation (0.5-5 Hz, 10-sec train), to nitric oxide (NO; 0.1-3 microM), to the NO donor, sodium nitroprusside (SNP; 5-500 nM), and to the cell-permeable analogue of cyclic guanosine monophosphate (cGMP), 8-bromo-cGMP (15 and 30 microM), were significantly smaller in muscles from diabetic rats than from control rats. Pretreatment with aminoguanidine hemisulphate (1 milligram drinking water) to inhibit AGE formation, did not alter the relaxant responses to nitrergic nerve stimulation, NO or SNP in tissues from control rats, or responses to NO or SNP in tissues from diabetic rats, however relaxations to nitrergic nerve stimulation were further reduced in tissues from diabetic rats. In anococcygeus muscles from untreated animals, a 20-min exposure to aminoguanidine (1 mM) in vitro had no effect on relaxations to nitrergic nerve stimulation. The results suggest that diabetes impairs nitrergic transmission in the rat anococcygeus at least partly through alterations in the cGMP-relaxation pathway. The impaired neurotransmission does not appear to be related to the formation of AGEs. PMID- 7870289 TI - Nitric oxide is a central mediator of penile erection. AB - In order to evaluate a possible role of brain nitric oxide (NO) on the control of penile erection, the effect of nitroglycerin, that is thought to act by producing NO, was studied on spontaneous penile erection in male rats. In addition the effect of drugs that prevent NO formation and/or activity such as NG-nitro-L arginine methyl ester (NAME) and methylene blue, on N-methyl-D-aspartic acid (NMDA)-, apomorphine- and oxytocin-induced penile erection was also studied. Nitroglycerin induced penile erection in a dose-dependent manner when given intracerebroventricularly (i.c.v.) (33-99 micrograms) or in the paraventricular nucleus of the hypothalamus (0.8-3.3 micrograms). Nitroglycerin-induced penile erection was prevented by the guanylate cyclase inhibitor methylene blue injected i.c.v. (200-400 micrograms) but not in the paraventricular nucleus of the hypothalamus (10-20 micrograms). Conversely, NMDA-, apomorphine- and oxytocin induced penile erection was prevented by NAME (150 micrograms) or methylene blue (400 micrograms) given i.c.v. NAME (20 micrograms), but not methylene blue (20 micrograms), was effective in preventing the behavioral response also when injected in the paraventricular nucleus. The present results suggest that NO is a common mediator of several neurotransmitters involved in the control of this primary male sexual function. PMID- 7870290 TI - The effects of a photosensitive nitric oxide donor on basal and electrically stimulated dopamine efflux from the rat striatum in vitro. AB - The reported effects of nitric oxide (NO) on dopamine release from the striatum are variable and its precise effect on striatal nerve terminals is unclear. In the present study a novel method of applying NO to brain tissue in situ was employed. Photo-activation of Roussin's Black Salt (RBS), retained in isolated perfused brain tissue, was used to release NO at will upon illumination. Basal and electrically-stimulated dopamine efflux from the rat striatum in vitro was measured in real time using fast cyclic voltammetry. Illumination of an RBS pre treated brain slice elicited a light intensity-related increase in basal dopamine efflux. Concomitantly there was a decrease in the level of electrically stimulated dopamine efflux. Illumination in the absence of RBS pre-treatment had no effect on basal or stimulated dopamine efflux. The increase in basal dopamine efflux upon photo-activation of RBS was reduced by the presence of 10 microM oxyhaemoglobin, but was insensitive to the removal of extracellular calcium or the addition of 1 microM sulpiride. The decrease in electrically-stimulated dopamine efflux following illumination was not affected by the presence of either oxyhaemoglobin or sulpiride. It is concluded that NO, produced by photo activation of RBS, releases dopamine from the rat striatum in vitro by a mechanism independent of extracellular calcium entry. PMID- 7870291 TI - Photolytic release of nitric oxide modulates NMDA receptor-mediated transmission but does not induce long-term potentiation at hippocampal synapses. AB - We have investigated the effects of photolytic release of nitric oxide (NO) on synaptic transmission in the hippocampal slice. Intracellular and extracellular recording techniques were used to monitor synaptic transmission in area CA1 of slices prepared from young rats and maintained in an interface chamber at 24 degrees C. N-methyl-D-aspartate (NMDA) receptor-mediated transmission was depressed, in a concentration- and haemoglobin-dependent manner, by NO released from perfusion fluid containing an inert photosensitive precursor, K2Ru(NO)Cl5, following exposure to a flash of near-UV light. However, conjunction of photolytic release of NO together with either weak high frequency stimulation, or strong stimulation in the presence of the NMDA receptor antagonist D(-)-2-amino-5 phosphonopentanoic acid (D(-)AP5), did not lead to a persistent enhancement of synaptic efficacy. These results establish that photolytically released NO can affect NMDA receptor-mediated transmission but do not support a role for NO as a retrograde messenger at CA1 synapses. PMID- 7870292 TI - Activation of the NO-cGMP signalling pathway depresses hippocampal synaptic transmission through an adenosine receptor-dependent mechanism. AB - Activation of the NO-cGMP pathway or adenosine receptors depresses reversibly synaptic transmission in the hippocampus. Here we demonstrate, using the selective A1 receptor antagonist DPCPX, a convergence in the mechanisms of action of the NO donor SNAP, the cGMP phosphodiesterase inhibitor zaprinast and adenosine. PMID- 7870293 TI - The amyloid precursor protein fragment His 657-Lys 676 inhibits noradrenaline- and enkephaline-induced suppression of voltage sensitive calcium currents in NG108-15 hybrid cells. AB - We have investigated the effects of the C-terminal amyloid precursor protein fragment His 657-Lys 676 upon calcium currents in NG108-15 neuroblastoma x glioma hybrid cells. The amyloid precursor protein fragment His 657-Lys 676 (1-10 microM) did not affect calcium currents per se, but clearly blocked the calcium current suppression mediated by both adrenergic alpha 2B- and opioid delta receptors in a concentration-dependent manner. The reverse amyloid precursor protein fragment Lys 676-His 657 and the shorter amyloid precursor protein fragment Gly 659-Lys 676 did not affect calcium current suppression by adrenergic alpha 2B- and opioid delta receptors. The similar interaction of C-terminal amyloid precursor protein with adrenergic alpha 2B- and opioid delta receptors suggest that the effect occurs downstream of the receptor, possibly via the GTP binding protein Go. PMID- 7870294 TI - Delta-opioid receptor gene expression in the mouse forebrain: localization in cholinergic neurons of the striatum. AB - Opioid peptides and opioid receptors, particularly the delta receptor, are abundant in the striatum where they contribute to the neuronal interactions, and are involved in various behavioral effects. The recent cloning of the delta opioid receptor now allows the identification of the striatal neurons that express it, and that are direct targets of endogenous opioid peptides such as enkephalins. In this context, we have used in situ hybridization histochemistry to determine the distribution of the delta-opioid receptor messenger RNA in the forebrain, and especially the phenotype of the neurons expressing the delta opioid receptor gene in the striatum. We show that the topgraphy of the neurons containing the delta-opioid receptor messenger RNA is similar to the topography of the neurons containing the choline acetyltransferase messenger RNA in the mouse forebrain. Comparison of adjacent serial sections demonstrates that the delta-opioid receptor gene is indeed expressed exclusively in cholinergic interneurons in the striatum. As these neurons also selectively express the substance P receptor gene, our data suggest that the striatal cholinergic interneurons are a common link in the interactions between the two striatal efferent populations, namely enkephalin and substance P neurons. PMID- 7870295 TI - Nonlinear relationship between impulse flow, dopamine release and dopamine elimination in the rat brain in vivo. AB - Central dopaminergic neurons exhibit two kinds of discharge activity: single spikes and bursts of two to six action potentials. Since these neurons can switch from one discharge pattern to the other whereas the mean discharge rate remains little affected, bursts may be more potent in triggering the release of their neurotransmitter, dopamine. Electrical stimulations mimicking the bursting pattern were actually twice as potent as regularly spaced stimulations to enhance the dopamine extracellular concentration. This suggested that dopamine release might be facilitated by increasing the impulse flow frequency. The high extracellular overflow evoked by a burst might also be due to accumulation of the released dopamine whereas, at lower frequencies, dopamine might be readily eliminated between every action potential. In the present study the dopamine overflow evoked by electrical stimulation of the dopaminergic pathway was measured in vivo by carbon fibre electrodes combined with continuous amperometry. We observed a small facilitation of the release per pulse during stimulations mimicking a burst but only in mesolimbic areas. The high extra-cellular dopamine level evoked by a burst was mainly due to accumulation of the released dopamine. PMID- 7870296 TI - Continuous in vivo monitoring of evoked dopamine release in the rat nucleus accumbens by amperometry. AB - The release of dopamine in the nucleus accumbens of anaesthetized rats was evoked either by electrical stimulation of the mesolimbic dopaminergic pathway or by local ejection of N-methyl-D-aspartate in the ventral tegmental area. Untreated carbon-fibre electrodes implanted in the nucleus accumbens were held at +400 mV versus a reference electrode, and the oxidation current was continuously monitored. Despite a poor selectivity to dopamine versus other oxidizable compounds such as ascorbic acid, the evoked responses were solely due to dopamine overflow in the extracellular fluid since they were closely correlated with the stimulations and exhibited all the expected characteristics related to a dopamine release. First, these effects were closely consistent with the anatomy of the mesolimbic dopaminergic system. Second, the responses to electrical stimulations were abolished by a tetrodotoxin ejection in the vicinity of the carbon-fibre electrode and they were strongly, but reversibly, diminished (60% decrease) when cadmium was substituted for calcium in an artificial cerebrospinal fluid ejected close to the electrode. Third, their maximal amplitudes were enhanced by amphetamine, pargyline, nomifensine and haloperidol. Fourth, inhibition of dopamine reuptake by nomifensine induced a five-fold decrease in the rate of decline of the evoked oxidation current. Fifth, contribution of noradrenaline and serotonin to the observed effects seems unlikely since specific reuptake blockers (desipramine and sertraline, respectively) did not alter them. Dopaminergic neurons discharge either in a single spike mode with a mean firing rate below 5 Hz or in a bursting pattern (intraburst frequency: 10 to 20 Hz).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870297 TI - Pharmacology and electrophysiology of a synchronous GABA-mediated potential in the human neocortex. AB - Spontaneous synchronous field potentials of negative polarity (duration = 200-700 ms, inter-event interval = 9.1 +/- 2.9 s; n = 27 slices) were recorded, during application of 4-aminopyridine (50 microM), from the superficial/middle layers of slices of human neocortex obtained in the course of neurosurgery for the relief of intractable seizures. The negative-going field potential corresponded to an intracellular long-lasting (duration = 200-1600 ms) depolarization that could be preceded by preceded by an excitatory postsynaptic potential-hyperpolarizing inhibitory postsynaptic potential sequence and followed by a long-lasting hyperpolarization. This synchronous activity continued to occur following blockade of excitatory synaptic transmission by excitatory amino acid receptor antagonists, but was greatly reduced and eventually disappeared during application of the GABAA receptor antagonist bicuculline methiodide. Simultaneous extracellular recordings from three sites in the slice located along an axis parallel to the pia showed that successive synchronous field potentials could originate from any of the three areas. They invaded the other two sites in c. 35.5% of the cases, while propagation to another site only or no propagation at all was observed, respectively, in 44.4% and 20% of instances. The velocity of lateral propagation of the synchronous field potential was 7.9 +/- 2.5 mm/s (range = 4.5-11.8 mm/s, n = 6). The modalities of origin and propagation remained the same after blockade of excitatory amino acid receptors. Under these conditions, however, there was a higher incidence of non-propagation and the velocity was significantly lower than in control (5.6 +/- 1.9 mm/s; range = 2.8 7.7 mm/s, n = 6). These data indicate that, in the human neocortex, 4 aminopyridine can reveal a synchronous field potential that correlates with an intracellular long-lasting depolarization and is mainly due to the activation of postsynaptic GABAA receptors. The action of excitatory amino acid receptors is not necessary for the generation and propagation of these GABA-mediated potentials. We propose that this potential represents a novel mechanism for synchronization and spread of neuronal activity, including seizure-like discharges in the human neocortex. PMID- 7870298 TI - Glutamate-induced intracellular calcium changes and neurotoxicity in cortical neurons in vitro: effect of chemical ischemia. AB - To study the role of calcium in neuronal death during ischemia, we examined the characteristics of intracellular Ca2+ ([Ca2+]i) changes in single rat forebrain neurons exposed for 5 min to glutamate (3 microM + 1 microM glycine), NMDA (30 microM + 1 microM glycine), kainate (100 microM) or high K+ (50 mM), under both normal and ischemic conditions. The parameters of [Ca2+]i change measured included peak [Ca2+]i level, plateau [Ca2+]i level, area under the [Ca2+]i response curve and time taken by [Ca2+]i to recover to 10% of the peak response. Under normal conditions, all the agonists studied produced similar [Ca2+]i changes. Chemical ischemia simulated by application of 5 mM KCN in glucose-free buffer had no effect on the basal level of [Ca2+]i, but significantly enhanced and prolonged the [Ca2+]i changes produced by all the agonists. However, in toxicity studies, chemical ischemia significantly potentiated the toxicity of only glutamate and N-methyl-D-aspartate. In correlation studies, all the neurons which died displayed an irreversible secondary [Ca2+]i load prior to loss of viability. These studies suggest that while Ca2+ entry may play a critical role in neuronal death, the magnitude of initial [Ca2+]i change does not predict the toxicity of an agonist in cortical neurons. PMID- 7870299 TI - Spatial working memory over long retention intervals: dependence on sustained cholinergic activation in the septohippocampal or nucleus basalis magnocellularis cortical pathways? AB - Previous direct neurochemical studies of the temporal dynamics of cholinergic activation in the septohippocampal and nucleus basalis magnocellularis-cortical pathways at various stages during repeated testing of mice with selective spatial reference or working memory protocols [Durkin and Toumane (1992), Behav. Brain Res. 50, 43-52] showed that the post-test durations of cholinergic activation in each pathway varied as a function of the type of memory tested and the level of task mastery. Since (i) the hippocampal formation is considered to constitute a critical component of a temporary memory buffer, and (ii) working memory items are not thought to be submitted to consolidation and permanent storage, we postulated that the duration of testing-induced cholinergic activation in the septohippocampal pathway may govern the maintenance of the working memory trace over the retention interval. In order to test directly this hypothesis C57 B1/6 mice were extensively trained (one trial/day, 25-30 days) on an identical selective working memory task to attain high levels of retention (> 80% correct), but using either 5 min (Group 1), or 60 min (Group 2) retention intervals. At various times (30 s-75 min) following the initial acquisition phase of the test, cholinergic activity in the hippocampus and frontal cortex was quantified using measures of high-affinity choline uptake. Whereas cholinergic activation was observed in both pathways at 30 s post-acquisition and throughout the 5 min retention interval in Group 1, the situation in Group 2 is different, activation of the septohippocampal pathway being maintained for only 15 min, while activation in the nucleus basalis magnocellularis-cortical pathway is maintained for the totality of the 1 h retention interval. The nucleus basalis magnocellularis-cortical cholinergic pathway, in addition to its role in long term reference memory storage processes may, thus, via an intervention in the temporal encoding of information, also subsume a complementary intermediate-term buffer storage role in working memory situations requiring retention intervals in excess of 15 min in mice. This secondary, "backup", function of the nucleus basalis magnocellularis-cortical pathway would thus liberate the septohippocampal complex from its primary active role in the temporary maintenance and/or accessibility of the working memory trace in these particular cases requiring long retention intervals. PMID- 7870300 TI - Cellular localization of type II Ca2+/calmodulin-dependent protein kinase in the rat basal ganglia and intrastriatal grafts derived from fetal striatal primordia, in comparison with that of Ca2+/calmodulin-regulated protein phosphatase, calcineurin. AB - We investigated immunohistochemically the cellular localization of multifunctional type II Ca2+/calmodulin-dependent protein kinase in the rat basal ganglia and intrastriatal grafts derived from fetal striatal primordia, in comparison with that of calcineurin, a reliable marker for striatal medium-sized spinous neurons. The type II Ca2+/calmodulin-dependent protein kinase-positive neurons were of medium size, with a mean diameter of 16.1 +/- microns (average +/ S.D., n = 72, range 13.6-18.3 microns) and comprised approximately 70% of the total neuronal population in the striatum. Light microscopy showed that the type II Ca2+/calmodulin-dependent protein kinase-positive cells had round, triangular or polygonal cell bodies with relatively little cytoplasm. Analysis of serial sections showed that type II Ca2+/calmodulin-dependent protein kinase and calcineurin immunoreactivities were co-localized in the striatal neurons examined with a similar distribution pattern. Type II Ca2+/calmodulin-dependent protein kinase-positive cells were always immunoreactive for calcineurin and cells negative for type II Ca2+/calmodulin-dependent protein kinase showed no apparent calcineurin immunoreactivity. Type II Ca2+/calmodulin-dependent protein kinase positive nerve fibers in the globus pallidus and substantia nigra almost disappeared following striatal ischemic injury produced by transient middle cerebral artery occlusion and cerebral hemitransection, respectively, suggesting that these immunopositive fibers were striatal projections. Thus, most type II Ca2+/calmodulin-dependent protein kinase-positive neurons in the rat striatum are considered to be of the medium-sized spinous type. Type II Ca2+/calmodulin dependent protein kinase or calcineurin immunoreactivity was also observed in a large number of neurons in transplants derived from fetal striatal primordia grafted into striatal ischemic lesions. In addition, type II Ca2+/calmodulin dependent protein kinase- or calcineurin-immunoreactive nerve fibers appeared in the deafferented globus pallidus of the host rats, suggesting that the striatopallidal pathway was reformed by striatal projection neurons of the transplants. This finding may also indicate that Ca2+/calmodulin-regulated enzymes are useful for tracing striatal projection fibers as endogenous marker proteins. PMID- 7870301 TI - Synaptic input and output of parvalbumin-immunoreactive neurons in the neostriatum of the rat. AB - Previous studies have demonstrated that the calcium-binding protein parvalbumin, is located within a population of GABAergic interneurons in the neostriatum of the rat. Anatomical studies have revealed that these cells receive asymmetrical synaptic input from terminals that are similar to identified cortical terminals and that they innervate neurons with the ultrastructural features of medium spiny cells. Furthermore, electrophysiological studies suggest that some GABAergic interneurons in the neostriatum receive direct excitatory input from the cortex and inhibit medium spiny cells following cortical stimulation. The main objectives of the present study were (i) to determine whether parvalbumin immunoreactive neurons in the rat receive direct synaptic input from the cortex, (ii) to determine whether parvalbumin-immunopositive axon terminals innervate identified striatal projection neurons and (iii) to chemically characterize this anatomical circuit at the fine structural level. Rats received stereotaxic injections of biocytin in the frontal cortex or injections of neurobiotin in the substantia nigra. Following an appropriate survival time, the animals were perfused and the brains were sectioned and treated to reveal the transported tracers. Sections containing the neostriatum were treated for simultaneous localization of the transported tracer and parvalbumin immunoreactivity. Tracer deposits in the cortex gave rise to massive terminal and fibre labelling in the neostriatum. Parvalbumin-immunoreactive elements located within fields of anterogradely labelled terminals were examined in the electron microscope and corticostriatal terminals were found to form asymmetrical synaptic specializations with all parts of parvalbumin-immunoreactive neurons that were examined. Tracer deposits in the substantia nigra produced retrograde labelling of a subpopulation of striatonigral neurons. Areas of the neostriatum and nucleus accumbens containing retrogradely labelled neurons and parvalbumin-immunoreactive structures were selected for electron microscopy. Parvalbumin-immunopositive axon terminals formed symmetrical synaptic specializations with the perikarya of retrogradely labelled medium spiny projection neurons. Postembedding immunocytochemistry for GABA revealed that parvalbumin-immunoreactive boutons in synaptic contact with medium spiny neurons were GABA-positive. These data demonstrate directly a neural circuit whereby cortical information may be passed to medium spiny cells, via GABAergic interneurons, in the form of inhibition and provide an anatomical substrate for the feed-forward inhibition that has been detected in spiny neurons in electrophysiological experiments. PMID- 7870302 TI - Production and characterization of polyclonal antibodies recognizing the intracytoplasmic third loop of the 5-hydroxytryptamine1A receptor. AB - The portion of the complementary DNA encoding the third intracellular loop of the rat 5-hydroxytryptamine1A (serotonin) receptor was subcloned into the vector pGEX KG and expressed in Escherichia coli as a fusion protein coupled with the glutathione S-transferase of Schistosoma japonicum. The fusion protein was purified on a glutathione-agarose affinity column and used to immunize rabbits for the production of polyclonal anti-5-hydroxytryptamine1A receptor antibodies. Enzyme-linked immunosorbent assay revealed that antibodies were produced as early as one month after the first injection of the fusion protein, and immune response plateaued at a maximum after the third (monthly) booster injection. These antibodies only marginally affected the specific binding of [3H]8-hydroxy-2-(di-n propyl-amino) tetralin to solubilized and membrane bound 5-hydroxytryptamine1A receptors, and did not interfere with serotonin-induced inhibition of forskolin stimulated adenylate cyclase negatively coupled to 5-hydroxytryptamine1A receptors in rat hippocampal membranes. However, antibodies were able to immunoprecipitate 5-hydroxytryptamine1A receptor binding sites solubilized from rat hippocampal membranes. The distribution of immunoautoradiographic labelling and immunohistochemical staining of rat brain sections exposed to the antibodies raised against the fusion protein superimposed to that of 5-hydroxytryptamine1A receptor binding sites labelled by specific radioligands, with marked enrichment in the limbic areas (dentate gyrus and CA1 area in the hippocampus, lateral septum, entorhinal cortex) and the anterior raphe nuclei. The differential cellular location of immunoreactivity within the hippocampus (where dendritic fields but not pyramidal cell somas were immunostained) and the median raphe nucleus (where the plasmic membrane of somas was strongly immunoreactive) suggests that the addressing of 5-hydroxytryptamine1A receptors might differ from one neuronal cell type to another. PMID- 7870303 TI - Selective expression of clusterin (SGP-2) and complement C1qB and C4 during responses to neurotoxins in vivo and in vitro. AB - This study concerns expression of the genes encoding three multifunctional proteins: clusterin and two complement cascade components, C1q and C4. Previous work from this and other laboratories has established that clusterin, Clq and C4 messenger RNAs are elevated during Alzheimer's disease, and in response to deafferenting and excitotoxic brain lesion. This study addresses hippocampal clusterin, ClqB and C4 expression in response to neurotoxins that caused selective neuron death. Kainate, which preferentially kills hippocampal CA3 pyramidal neurons but not dentate gyrus granule neurons induced clusterin immunoreactivity in CA1 and CA3 pyramidal neurons and adjacent astrocytes, but not in dentate gyrus granule neurons. In contrast, colchicine, which preferentially kills the dentate gyrus granule neurons, induced clusterin immunoreactivity in the local neuropil as punctate deposits, but not in the surviving or degenerating dentate gyrus granule neurons. Clusterin messenger RNA was increased in astrocytes. ClqB and C4 messenger RNAs increased within 48 h after kainate injections, particularly in the CA3 pyramidal layer, less in the dentate gyrus-CA4, and less in CA1. Clq immunoreactivity was detected in CA1 pyramidal neurons and also as small punctate deposits in the CA1 region at eight and 14 days after kainate. The increase of both clusterin and ClqB messenger RNAs after kainate injections was blocked by barbiturates that prevented seizures and neurodegeneration. In primary hippocampal neuronal cultures treated with glutamate, a subpopulation of cultured neurons that survived glutamate toxicity also had parallel elevations of clusterin and ClqB messenger RNA. In conclusion, cytotoxins that target selective hippocampal neurons increase the expression of both clusterin and ClqB in vivo and in vitro. These results show that elevations of clusterin messenger RNA or protein can be dissociated from each other and from cell death. These increased messenger RNAs were associated with immunoreactive deposits that differed by cell type and intra- versus extracellular locations. These results suggest that the complement system is involved in brain responses to injury. PMID- 7870304 TI - Long-latency event-related potentials in rats: effects of task and stimulus parameters. AB - Animal models of event-related potentials have recently been developed in rats in order to gain further understanding of the psychobiological variables which underlie these waveforms. In the present study, unanesthetized male Wistar rats, chronically implanted with electrodes, were utilized in order to: (i) compare event-related potentials recorded following the presentation of passively presented auditory stimuli from different neocortical, hippocampal and perihippocampal sites; (ii) test the effects of changes in stimulus probability and loudness on event-related potentials recorded from those sites; and (iii) record event-related potentials from rats who were actively performing in a tone discrimination task. The results of these studies showed that in all electrode sites (frontal cortex, parietal cortex, entorhinal cortex, hippocampus) a series of large amplitude potentials in the 10-200 ms latency range could be recorded in response to passively presented stimuli. Late positive potentials in the 300-400 ms range were only identified in recordings from the posterior cortex, entorhinal area, and dorsal hippocampus. Some of these late positive components were also found to be sensitive to changes in stimulus probability. A similar series of waves were detected in a paradigm where rats were required to actively discriminate between two tones; however, the morphologies of the waveforms were found to be more distinct. These studies suggest that rats may be good subjects for the exploration of the neural origins of event-related potentials. These studies demonstrate that rats performing in an auditory discrimination task can generate electrophysiological potentials which are time locked to the onset of a "cognitively relevant" stimulus (event-related potentials). These potentials can be recorded in limbic (hippocampus and amygdala) and cortical (parietal cortex) brain sites. The event-related potentials recorded in rats respond to changes in stimulus parameters in a similar fashion to those previously described in monkeys and human subjects. The identification of a rat model of event-related potentials provides an opportunity to further explore the neural origins of event-related potentials, to estimate the role of genetics in determining individual variation in waveforms, as well as to provide electrophysiological assays of the effects of various drugs on neurosensory and cognitive processing. PMID- 7870305 TI - Electrophysiological investigation of thalamic neuronal mechanisms of motor disorders in parkinsonism: an influence of D2ergic transmission blockade on excitation and inhibition of relay neurons in motor thalamic nuclei of cat. AB - In acute experiments on cats anaesthetized with ketamine (25 mg/kg, i.m.) and immobilized with myorelaxine (2 mg/kg, i.v.) the activity of two groups of motor thalamic (nucleus ventralis anterior thalami-nucleus ventralis lateralis thalami) relay neurons was studied. The neurons (n = 7) receiving afferents from deep cerebellar nuclei and projecting to the motor area 4 gamma were included in the first group, and those (n = 12) receiving afferents from nucleus entopeduncularis and projecting to the supplementary motor area 6 were included in the second one. All changes in the background activity and reactions to cerebellothalamic or nucleus entopeduncularis stimulation developing under the influence of D2 receptor antagonist haloperidol (1.5-1.7 mg/kg, i.v.) have been studied in the same cell. Under haloperidol influence both groups of neurons showed a reliable decrease of background activity and generation of high frequency discharges accompanied by a shift in the mode of interspike interval histograms. A regular decrease of probability and increase of response latencies after stimulation of afferent input were observed in neurons receiving afferents from the cerebellum. In nucleus ventralis anterior thalami-nucleus ventralis lateralis thalami neurons with an inhibitory input from nucleus entopeduncularis, a shortening of inhibition from 17.5 +/- 3.6 to 9.1 +/- 1.8 ms (P < 0.05) under the haloperidol influence was evident. If the inhibition evoked by nucleus entopeduncularis stimulation consisted of two phases separated by a period of excitation (n = 4), the duration of the second phase of inhibition after haloperidol injection regularly increased and the excitation separating the phase of inhibition after haloperidol injection regularly increased and the excitation separating the phases of inhibition became more prominent. Observation on the spontaneous activity and reactions of the same neuron for 2 h or more showed a gradual moderation of the changes evoked by haloperidol. On the basis of data obtained it is concluded that the blockade of D2 receptors is followed by the increase of inhibitory processes in the relay neurons of motor thalamic nuclei. The suggestion is discussed that during the blockade of D2 receptors afferent impulsation to the motor cortex is being restricted and its influence on segmental apparatus of the spinal cord decreases. These conditions are beneficial for the development of spasticity (rigidity). At the same time, hyperpolarization of the relay neurons promotes the development of oscillatory processes at least in part of them and creates conditions for forming of tremor generators. PMID- 7870306 TI - The effects of [Arg8]vasopressin and [Arg8]vasotocin on the firing rate of suprachiasmatic neurons in vitro. AB - The excitatory effect of [Arg8]-vasopressin and its potential contribution to the circadian cycle of electrical activity in the suprachiasmatic nucleus of the rat was investigated using extracellular recordings from hypothalamic slices from virgin female rats. The majority of neurons tested for their responses to vasopressin and [Arg8]-vasotocin displayed coincident, dose-dependent excitation by both peptides, although the relative efficacy varied between neurons, with some showing a highly preferential excitation by vasotocin. Perifusion with the vasopressin receptor antagonist d(CH2)5[Tyr(OEt)2,Val4,Cit8]-vasopressin was able to block the majority of responses to vasopressin or vasotocin (20/25), and similar excitation could be induced by the selective agonist [Phe2,Orn8] vasotocin, indicating a mainly V1 receptor-mediated effect. Few neurons (3/27; 11%) responded to the oxytocin-specific agonist, [Thr4,Gly7]-oxytocin, suggesting a low occurrence of oxytocin receptors. In addition to blocking the action of exogenous vasopressin, the V1 antagonist caused a reversible suppression of spontaneous basal activity in 7/25 cases, consistent with the presence of an endogenous excitatory vasopressin tone. In agreement with previous reports, the activity of suprachiasmatic nucleus neurons showed a significant correlation between spontaneous activity and the light-dark cycle, with activity decreasing during the subjective dark phase. When neurons were divided on the basis of their response to vasopressin and/or vasotocin, the peptide-sensitive neurons continued to show a strong correlation (r = 0.513, P < 0.01) while the insensitive neurons showed no correlation (r = 0.136, P > 0.05). These data confirm the presence of V1 type receptors in the suprachiasmatic nucleus and also indicate a small number of neurons possessing additional classes of receptor selective for either oxytocin or vasotocin. Contrary to previous reports, they also demonstrate that endogenous vasopressin tonically excites suprachiasmatic nucleus neurons. The fact that vasopressin-sensitive (but not vasopressin-insensitive) neurons show a level of basal activity correlated with time, suggests that this tone may contribute to the circadian cycle of electrical activity in the suprachiasmatic nucleus. PMID- 7870307 TI - Occurrence of heat shock response in deafferented neurons in the substantia nigra of rats. AB - The substantia nigra is innervated by massive inhibitory GABAergic projections from the striatum and globus pallidus, deafferentation of which is supposed to lead to anterograde trans-synaptic degeneration of the nigral neurons. An immunohistochemical method was used to examine the induction of 72,000 mol. wt heat shock protein in the substantia nigra following cerebral hemitransection or transient middle cerebral artery occlusion. At three and four days post transection, strong immunoreactivity for 72,000 mol. wt heat shock protein was found in the ipsilateral substantia nigra pars reticulata. Light microscopic observation revealed a number of pars reticulata neurons showing strong immunoreactivity for 72,000 mol. wt heat shock protein in their perikarya and proximal processes. In addition, Golgi-like stained neurons with dystrophic features were occasionally observed in the ipsilateral substantia nigra pars reticulata. The immunoreactivity for 72,000 mol. wt heat shock protein in the ipsilateral pars reticulata gradually declined and almost disappeared by 15 days after transection. No apparent induction of 72,000 mol. wt heat shock protein was found in the substantia nigra pars compacta throughout the time period examined. Massive striatal ischemic injury produced by transient middle cerebral artery occlusion also induced expression of 72,000 mol. wt heat shock protein in the pars reticulata neurons three and four days postoperatively. These findings suggest that deafferentation of the striatal or striatopallidal inputs per se is a harmful stress for the substantia nigra pars reticulata neurons, inducing 72,000 mol. wt heat shock protein synthesis. The present data may contribute to our understanding of the molecular basis of the pathomechanism of the transneuronal regression of substantia nigra pars reticulata neurons, which may occur after removal of inhibitory GABAergic inputs. PMID- 7870308 TI - Differential up-regulation of voltage-dependent Na+ channels induced by phenytoin in brains of genetically seizure-susceptible (E1) and control (ddY) mice. AB - We investigated the effect of in vivo administration of an antiepileptic drug, phenytoin, on the saxitoxin binding capacity of receptor site 1 of the Na+ channel alpha-subunit, and the expression activity of the channel messenger RNA in epileptic El mouse brains, as compared with parental ddY mice. Subchronic treatment with phenytoin (25 mg/kg per day) for 14 days increased the [3H]saxitoxin binding to brain-derived synaptic membranes of both El and control ddY mice in a time dependent manner. This increase plateaued at 21 +/- 4% in El mice and 28 +/- 3% in ddY control mice after administration of phenytoin for seven days. After cessation of treatment with phenytoin, [3H]saxitoxin binding capacity returned to the basal level within two weeks in both ddY and El brains. Scatchard plot analysis revealed that the phenytoin treatment caused a 20-30% increase in maximum binding capacity of [3H]saxitoxin binding without any change in equilibrium dissociation constant in the brain cortical synaptic membranes of both epileptic El and control ddY mice. A single injection of phenytoin (25 mg/kg) elevated the level of Na+ channel messenger RNA within 1 h in ddY mouse brains. The increase in Na+ channel messenger RNA reached a peak (about 80% increase) after 5 h of phenytoin administration in a concentration-dependent manner (6.25-50 mg/kg). On the other hand, in El mouse brains, Na+ channel messenger RNA was not elevated until more than 5 h after phenytoin injection, and was increased by only about 33%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870309 TI - Impairment of GABAA receptor function by N-methyl-D-aspartate-mediated calcium influx in isolated CA1 pyramidal cells. AB - Mechanisms of regulation of GABAA receptor function by intracellular calcium ([Ca2+]i) were examined in cell somata and apical dendrites of pyramidal cells, acutely dissociated from the CA1 hippocampal subfield of adult guinea-pigs. GABAA receptor-mediated currents were measured by whole-cell clamp recordings. N-methyl D-aspartate receptor-mediated currents were used as conditioning source of calcium influx. Peak amplitudes of somatic GABAA whole-cell currents were reduced to about 15% of control values when net inward charge accumulation by N-methyl-D aspartate currents reached 1.85 nC. A similar decline of GABAA currents was observed in dendritic recordings. The N-methyl-D-aspartate-mediated reduction of somatic and dendritic GABAA currents was accompanied by a well correlated decrease in peak and chord conductances. Pharmacological blockade of N-methyl-D aspartate currents by 2-amino-5-phosphonopentanoic acid prevented the N-methyl-D aspartate-mediated suppression of GABAA responses. The N-methyl-D-aspartate effect was mediated by the calcium component of N-methyl-D-aspartate receptor mediated currents as demonstrated by a lack of effect in the absence of extracellular calcium and faster N-methyl-D-aspartate-mediated suppression of GABAA responses in lower intracellular 1,2-bis(2-aminophenoxy)ethane-N,N,N',N" tetra-acetate. N-methyl-D-aspartate-mediated suppression of GABAA currents was significantly less expressed when intracellular ATP was replaced by its analog adenosine 5'-O-(3-thiotriphosphate) and when the specific phosphatase 2B inhibitor cypermethrin was added intracellularly. The reduction of GABAA responses persisted after cessation of N-methyl-D-aspartate-mediated calcium influx, indicating a long-term action of N-methyl-D-aspartate on GABAA responses. Voltage-activated calcium currents did not affect GABAA responses under the experimental conditions applied. In conclusion, the data presented show that calcium influxes through N-methyl-D-aspartate receptor channels result in long term suppression of GABAA receptor function in CA1 pyramidal cells. Intracellular mechanisms of N-methyl-D-aspartate-mediated reduction of GABAA conductances involve activation of phosphatase 2B and consecutive dephosphorylation of the GABAA receptor or a closely associated GABAA receptor-regulating enzyme. Possible mechanisms of such a distinct N-methyl-D-aspartate-dependent calcium signalling pathway in the dephosphorylation-dependent suppression or GABAA receptor function are discussed. PMID- 7870310 TI - Immunohistochemical localization of mu-opioid receptors in rat brain using antibodies generated against a peptide sequence present in a purified mu-opioid binding protein. AB - Light-microscope visualization in rat brain of a pattern of distribution of immunoreactivity, which included immunolabeled perikarya and beaded processes, was achieved using an immunoaffinity purified polyclonal antibody, Ab165, which recognizes the amino acid sequence, IRNLRQDRSKYY, found in the mu-opioid binding protein purified in our laboratory. Immunohistochemical staining with Ab165 was carried out by the avidin-biotin procedure. Antibody, preabsorbed with antigen, served as control. Extensive immunoreactivity was seen in the hippocampal formation, the amygdaloid complex, the striatal complex, cortical regions, select areas of the thalamus and hypothalamus and in laminae I and II of the dorsal horn in spinal cord. The distribution of immunoreactivity in the rat brain of antibody 165, which recognizes a purified mu-opioid binding protein, is concordant with the distribution of mu-opioid binding sites as determined by other laboratories in autoradiographic, electrophysiological and immunocytochemical studies. These findings have enabled us to distinguish areas possessing large fields of mu opioid receptor containing cell bodies from areas possessing dense networks of immunolabeled neuronal processes or mixtures of both. PMID- 7870311 TI - Mapping and computer assisted morphometry and microdensitometry of glucocorticoid receptor immunoreactive neurons and glial cells in the rat central nervous system. AB - By means of a monoclonal mouse immunoglobulin G2a antibody against the rat liver glucocorticoid receptor and the indirect immunoperoxidase technique, the distribution of glucocorticoid receptors in neuronal and glial cell populations was mapped in the central nervous system of the male rat. The mapping was complemented by computer-assisted morphometric and microdensitometric evaluation of glucocorticoid receptor immunoreactivity in many brain regions. The quantitative analysis allowed us to achieve for the first time an objective characterization of glucocorticoid receptor distribution in the CNS, thus avoiding the ambiguities of previous mapping studies based on subjective evaluations. In addition, a taxonomic analysis of central nervous system regions containing glucocorticoid receptor immunoreactivity was carried out utilizing the quantitative parameters obtained in the morphometric evaluation. Nuclei of neuronal and glial cells containing glucocorticoid receptor immunoreactivity were detected in a widespread, but still highly heterogeneous, fashion in the central nervous system, underlining the view that glucocorticoids can control a large number of central nervous system target cells via effects on gene expression. Many nerve cell populations have been shown to contain substantial amounts of nuclear glucocorticoid receptor immunoreactivity, whereas only a low density of glial cells, in both gray and white matter, show nuclear glucocorticoid receptor immunoreactivity. Thus, in most brain areas, the major target for glucocorticoids appears to be the nerve cells. Interestingly, an inverse correlation was found in the regional density of glucocorticoid receptor-immunoreactive nerve and glial cells, suggesting that glucocorticoids may influence a brain area either via glial cells or, more frequently, via nerve cells. The results on mapping highlight the impact of glucocorticoids in areas both traditionally and not traditionally involved in stress responses. The distribution of glucocorticoid receptor immunoreactivity also emphasizes a role of glucocorticoids in the regulation of the afferent regions of the basal ganglia and the cerebellar cortex, and of both afferent and efferent layers of the cerebral cortex. Glucocorticoid receptor immunoreactivity is widely distributed over the thalamus, probably leading to modulation of activity in the various thalamocortical pathways transmitting inter alia specific sensory information to the cerebral cortex. Many unspecific afferents to the cerebral cortex are potentially regulated by glucocorticoid receptors such as the noradrenaline and 5 hydroxytryptamine afferents, since their nerve cells of origin contain strong glucocorticoid receptor immunoreactivity. Eight brain regions involving sensory, motor and limbic areas were shown to have a similarity with regard to glucocorticoid receptor-immunoreactive parameters at the level of 95%. The density of glucocorticoid receptor-immunoreactive nerve cells appeared to be the main factor in determining such a very high level of similarity. Overall, our results emphasize that glucocorticoids may appropriately tune networks of different areas to obtain optimal integration and in this way improve survival of the animal under challenging conditions. PMID- 7870312 TI - Localization of cellular retinoid-binding proteins suggests specific roles for retinoids in the adult central nervous system. AB - Retinoic acid, the active metabolite of retinoids (vitamin A compounds), is thought to act as a gene regulator via ligand-activated transcription factors. In order to investigate possible roles of retinoids and retinoid-controlled gene expression in brain function, we have used immunohistochemistry to localize the possible presence of two intracellular retinoid-binding proteins, cellular retinol-binding protein type I and cellular retinoic acid-binding protein type I, in the adult rat central nervous system. We find a widespread, yet distinct, presence of these two binding proteins in the brain and spinal cord. Most of the immunoreactivity is neuronal, including cell somata, as well as dendritic and axonal processes and axon terminals. Cellular retinol-binding protein type I immunoreactivity is also found in the walls of cerebral blood vessels, the meninges, the choroid plexus, certain ependymal cells, tanocytes and certain other glial elements. The cellular retinol-binding protein type I- and cellular retinoic acid-binding protein type I-immunoreactivity patterns appear to be almost exclusively non-overlapping. Very strong cellular retinol-binding protein type I-immunoreactivity is found in the dendritic layers of the hippocampal formation and dentate gyrus. Cellular retinol-binding protein type I immunoreactivity is also present in layer 5 cortical pyramidal neurons and neurons in the glomerular layer of the olfactory bulb. Many other areas, e.g. hypothalamic nuclei and amygdala areas, contain networks of varicose cellular retinol-binding protein type I-immunoreactive nerve fibers. The medial amygdaloid nucleus contains strongly cellular retinol-binding protein type I-positive neurons. Cellular retinoic acid-binding protein type I-immunoreactivity is more restricted in the adult brain. Strong cellular retinoic acid-binding protein type I-immunoreactivity is, however, found in a population of medium-sized neurons scattered throughout the striatum, in neurons in the glomerular layer of the olfactory bulb, the olfactory nerve and in a group of nerve cells close to the third ventricle in hypothalamus. The remarkably selective patterns of cellular retinol-binding protein type I- and cellular retinoic acid-binding protein type I immunoreactivity discovered in the adult rat brain suggest that retinoids have important roles as regulators of gene expression in normal brain function. The high levels of cellular retinol-binding protein type I-immunoreactivity found in hippocampus suggest that one such role might relate to brain plasticity. PMID- 7870313 TI - Distribution of the messenger RNA for the prostaglandin E receptor subtype EP3 in the mouse nervous system. AB - Distribution of the messenger RNA for the prostaglandin E receptor subtype EP3 was investigated by in situ hybridization in the nervous system of the mouse. The hybridization signals for EP3 were widely distributed in the brain and sensory ganglia and specifically localized to neurons. In the dorsal root and trigeminal ganglia, about half of the neurons were labeled intensely. In the brain, intensely labeled neurons were found in Ammon's horn, the preoptic nuclei, lateral hypothalamic area, dorsomedial hypothalamic nucleus, lateral mammillary nucleus, entopeduncular nucleus, substantia nigra pars compacta, locus coeruleus and raphe nuclei. Moderately labeled neurons were seen in the mitral cell layer of the main olfactory bulb, layer V of the entorhinal and parasubicular cortices, layers V and VI of the cerebral neocortex, nuclei of the diagonal band, magnocellular preoptic nucleus, globus pallidus and lateral parabrachial nucleus. In the thalamus, moderately labeled neurons were distributed in the anterior, ventromedial, laterodorsal, paraventricular and central medial nuclei. Based on these distributions, we suggest that EP3 not only mediates prostaglandin E2 signals evoked by blood-borne cytokines in the areas poor in the blood-brain barrier, but also responds to those formed intrinsically within the brain to modulate various neuronal activities. Possible EP3 actions are discussed in relation to the reported neuronal activities of prostaglandin E2 in the brain. PMID- 7870314 TI - Localization of nicotinic cholinergic receptors in rat brain: autoradiographic studies with [3H]cytisine. AB - There is a great deal of interest in the role of nicotinic acetylcholine receptors in the central nervous system, although their function is not well understood at present. Currently, central nicotinic receptors can be classified broadly as either alpha-bungarotoxin binding sites with low affinity for acetylcholine agonists, or as high-affinity agonist binding sites with low affinity for alpha-bungarotoxin. Neuronal nicotinic receptors with a high affinity for agonists are distributed widely in the central nervous system. Evidence from molecular biology and electrophysiology suggests that multiple nicotinic receptor types exist in the brain. In this study we have used the agonist [3H]cytisine as a ligand for autoradiography to generate a detailed quantitative map of the high-affinity agonist binding nicotinic receptor in the rat brain. Optimized binding conditions, characterization of the kinetic and equilibrium binding properties, and demonstration of the nicotinic pharmacology of this binding site in tissue sections confirm the usefulness of [3H]Cytisine as a ligand for nicotinic receptor autoradiography. [3H]Cytisine autoradiography provides excellent anatomic resolution with very low non-specific binding. This property has allowed us to describe variations in receptor density within subnuclei and gradients of receptor density in larger brain regions. Data from several studies suggest that the predominant high-affinity agonist binding nicotine receptor in the central nervous system is composed of the alpha 4 and beta 2 subunits. The data in the current study are consistent with the suggestion that [3H]cytisine labels only the alpha 4 beta 2 nicotinic receptor with high affinity, offering the possibility of localizing a specific nicotinic receptor subtype in the central nervous system. In summary, we characterize the optimum experimental conditions for the use of [3H]cytisine in tissue section autoradiography. [3H]Cytisine proves to be an excellent marker for nicotinic cholinergic receptors with a very high affinity and very low background. We provide a detailed quantitative characterization of nicotinic receptor density in the rat central nervous system and we find there are significant variations and gradients in receptor density within specific brain regions, including subregions previously thought to be homogeneous. PMID- 7870315 TI - Expression and distribution of hsp71 and hsc73 messenger RNAs in rat brain following heat shock: effect of dizocilpine maleate. AB - Induction of hsp71 mRNA, coding for the inducible heat shock protein HSP71, and the constitutively expressed, hsc73 mRNA coding for the heat shock cognate protein HSC73 were studied after heat shock using northern blotting and in situ hybridization. Two cDNA oligonucleotides complementary to the messenger RNAs for hsp71 and hsc73 and suitable for in situ hybridization were designed and shown to hybridize selectively to their respective mRNAs. The inducible hsp71 was rapidly synthesized in brain after heat shock and disappeared in 6 h. A high level of expression was observed first in the dentate granule cell layer and then slightly later in the hippocampal pyramidal cell layer. There was also a dramatic increase in the granular layer of the cerebellar cortex. There was a more modest increase in expression of hsc73 after heat shock in forebrain and in cerebellum (granular layer). The N-methyl-D-aspartate receptor antagonist dizocilpine maleate (0.5 mg/kg, i.p.), given 15 min before heat shock, significantly reduced the expression of hsp71 but had no effect on hsc73. These results suggest that glutamate plays a role in heat shock-induced expression of hsp71 in brain. PMID- 7870316 TI - Influence of ATP and ATP agonists on the physiology of the isolated semicircular canal of the frog (Rana pipiens). AB - In the present study, the influence of extracellular ATP and ATP agonists in the physiology of the vestibular organs was examined, using the in vitro model of the isolated semicircular canal of the frog (Rana pipiens). The firing activity of the afferent nerve, the d.c. nerve potential and the transepithelial potential were measured in the absence and presence of mechanical stimulation of the sensory epithelium. Administration of ATP into the perilymphatic compartment, from 10(-12) to 10(-3) M, increased the firing rate of the afferent fibers recorded in the absence of mechanical stimulation. Recordings of the d.c. nerve potential indicated that the afferent fibers were hyperpolarized. The presence of the purine also modified the transepithelial potential. During mechanical stimulation of the sensory epithelium, both the evoked afferent firing and the evoked variation of the d.c. nerve potential were reduced in the presence of ATP. However, ATP did not effect the evoked modulation of the transepithelial potential, evoked by the mechanical stimulation. Administration of the P2x purinoceptor agonists, alpha, beta-methylene-ATP and beta, gamma-methylene-ATP, at concentrations between 10(-12) and 10(-3) M, did not significantly modify the different bioelectrical activities investigated. In contrast, 2-methylthio-ATP, a P2y purinoceptor agonist, more potent and efficacious than ATP in its effect on the spontaneous firing. Concurrently, no modification of the d.c. nerve potential, the transepithelial potential and their variation during mechanical stimulation was observed. In opposition to the ATP effect, the total amplitude of the evoked firing was increased in the presence of 2-methylthio-ATP. These data suggest that extracellular ATP, present in the perilymphatic compartment, may act as a neuromodulator in the vestibular physiology. The effects of the purine appear to be mediated by the activation of a P2y subtype of purinoceptor. The absence of an effect of ATP and 2-methylthio-ATP on the evoked variation of the transepithelial potential suggest that the purine did not affect the processes responsible for the generation of the receptor potential but more likely modified the mechanisms involved in the release of the neurotransmitter from the hair cells and/or acted on the afferent endings. PMID- 7870317 TI - Pneumonia in military recruits. AB - Lower respiratory disease is a major source of morbidity in military recruits, with hospitalization rates for pneumonia more than 30 times that of the non recruit population. The etiologic agent remains unknown in over 75% of cases. This study prospectively examined the etiology of pneumonia among recruits at Naval Training Center, San Diego, California. Recruits presenting with cough, fever, or shortness of breath and pulmonary infiltrates on chest X-ray were eligible for enrollment. A standardized scoring form and focused physical exam were completed on each subject. Sputum specimens were obtained for Gram's stain and culture, DNA probing for Legionella and Mycoplasma species, and direct fluorescent antibody staining for Legionella. Acute and convalescent serologies were performed for adenovirus, influenza A and B, Mycoplasma pneumoniae, Chlamydia group, and respiratory syncytial virus. Of 110 eligible patients, 100 consented to enrollment and 75 patients completed the study. Etiologic diagnoses were obtained in 40 of the patients (53%). M. pneumoniae, Haemophilus influenzae, and viruses accounted for the majority of infections. Mixed infections were seen in six patients. Forty-seven percent of patients had no diagnosis established. Pneumonia in this series of military recruits was frequently caused by M. pneumoniae and H. influenzae. Fifty percent of cases were undiagnosed with routinely available laboratory methods. Further studies are warranted to more clearly define the etiologic agents of recruit pneumonia and the utility of prophylactic measures. PMID- 7870318 TI - Reserve unit mobilization trauma. AB - Iraq's invasion of Kuwait in August 1990 caused much speculation that military Reserve units such as the 12th USAF Contingency Hospital would be called to active duty in the event of a war. Feelings and attitudes of personnel in the 12th Contingency Hospital were measured with a survey questionnaire in October 1990, 3 months prior to the mobilization date. The same questionnaire was administered in June 1991, about 2 months after the unit was demobilized. Indicators of increased tension, fear, and discouragement changed dramatically in the pre- and post-activation surveys. Some interesting rank group findings were noted. Results of the surveys point the way toward future studies to better understand what the specific emotional aspects of mobilizing a Reserve unit are and what can be done to ameliorate negative factors and to enhance constructive coping with problem areas. PMID- 7870319 TI - Persian Gulf War amputees: injuries and rehabilitative needs. AB - This study describes the injuries, complications, functional limitations, and rehabilitative needs of amputees managed at Walter Reed Army Medical Center during the Persian Gulf conflict (1991). Fourteen amputees were treated sustaining 21 amputations with 18 lower-limb and 3 upper-limb amputations. In six casualties there were multiple amputations. Battle injuries were the cause in 79%. Nerve injuries occurred in 79%, phantom pain in 64%, and functional limitations (ambulation and activities of daily living [ADLs]) were present in all casualties. Contractures were noted in 86%. Skin traction for open wounds was lacking in all but one case. With comprehensive rehabilitation, all casualties achieved independent ambulation, and 93% were independent in all ADLs at discharge, with one below-knee amputee successfully returning to duty. These findings highlight the need for education of military health care providers in skin traction techniques, and provision of multidisciplinary rehabilitative care for these casualties. PMID- 7870320 TI - Lao People's Democratic Republic Veterinary Public Health Project. AB - From May 21 to June 4, 1993, a collaborative training project involving U.S. Army veterinary personnel, the Lao-American Integrated Rural Development Project, and the Lao Department of Livestock and Veterinary Services occurred in the Houa Muang District of Houa Phan Province in northeastern Laos. The project focus was control of the major animal diseases of economic or public health importance in the area to include, but not limited to, hemorrhagic septicemia, anthrax, swine fever (hog cholera), and Newcastle disease. The project provided Lao veterinary personnel and villagers with didactic training and field demonstrations in disease control practices. Supplies and equipment necessary to continue disease control activities were provided to the district at the conclusion of the training and field demonstrations. The project was designed to be compatible with disease reporting and surveillance systems at district, province, and national levels and be exportable to other districts and provinces. In addition to disease control efforts, blood and fecal parasite surveys were conducted. PMID- 7870321 TI - Determinants of achievement in stair climbing as an exercise test. AB - Physicians routinely discuss pulmonary function and its impact on prognosis or operative risk. Although many studies have related various measures of pulmonary function to postoperative outcome, there has been no study designed to determine which of the spirometric measures of pulmonary function tests reflects the actual abstract idea of pure pulmonary function. A homogeneous population of 70 male patients was subjected to pulmonary function tests and a simple stair climb. Measures of pulmonary function (including FEV1, FEV1%, FVC, FVC%, and MVV%) were factor analyzed in a measurement model of pulmonary function to obtain reliability and validity estimates in predicting performance on a simple stair climb test. The analysis revealed several interesting aspects concerning the relative importance of the various spirometric measures of pulmonary function tests. The validity estimates of the pulmonary function measures were as follows: FEV1% = 0.917; FEV1 = 0.886; MVV% = 0.769; FVC% = 0.715; FVC = 0.694. Analysis indicates that the FEV1% was the single best spirometric indicator of pulmonary function when predicting the physiologic outcome (followed closely by the FEV1). In addition, the various spirometric measures of pulmonary function were not equally valid nor interchangeable in such analysis. Although the number of stairs climbed correlates well with pulmonary function (r = 0.626), the coefficient of non-determination (i.e., 1-r2) suggests that about 61% of the performance on the stair climb may be explained by other parameters (i.e., cardiac function, determination, altitude, etc.). PMID- 7870322 TI - Psychiatric medications for deployment. AB - Standard medical sick-cell chests used in the military contain either outdated or no psychiatric medications. Yet certain psychiatric medications are either useful or essential for the field and deployment. This article discusses suitable medications for both psychiatric emergencies and for chronic treatment of depression or anxiety. Psychiatric medications to avoid in deployment are also listed. Some dosing guidelines are provided. The article ends with a proposed "psychiatric sick-call chest" to be prepared in advance of deployment. PMID- 7870323 TI - Needs assessment for advanced practice nurses for the uniformed services. AB - An assessment was made of the need for advanced practice nurses (APNs) in the uniformed services of the Department of Defense and the United States Public Health Service. The purpose of the assessment was to determine the role of the Graduate School of Nursing (GSN) at the Uniformed Services University of the Health Sciences in educating APNs for the uniformed services. The assessment focused on three categories of APNs: certified registered nurse anesthetists (CRNAs), certified nurse-midwives (CNMs), and nurse practitioners (NPs). The assessment found that current authorizations for APNs in the three military services exceeded inventory by 192 APNs: 148 CRNAs, 4 CNMs, and 40 NPs. In addition, losses through attrition in fiscal year 1993 were 154 APNs: 97 CRNAs, 7 CNMs, and 50 NPs. Thus, there is a need for educational support to prepare APNs for the uniformed services. The GSN can usefully supplement other educational programs in meeting this need. PMID- 7870324 TI - Vitamin and mineral supplementation during pregnancy. AB - To determine the prevalence of individual vitamin and mineral supplement use during pregnancy and their relationships with selected characteristics of mothers, data from the 1988 National Maternal and Infant Health Survey were analyzed. The responses of 18,549 mothers were used in the analysis, which consisted of both univariate and multivariate statistical analyses. The prevalence of use for each of six supplements varied from 1.89% for zinc to 33.45% for iron. The use of these supplements did not appear to be strongly intercorrelated. Young age was associated with iron use, black race was associated with iron and vitamin A supplementation, and prenatal care and Women with Infants and Children food were associated with iron and vitamin A intake. Smoking was associated with folic acid and iron use, alcohol consumption was associated with folic acid use, and low family income was associated with iron use. The findings of the study may be useful in the future for more specific epidemiologic and clinical studies on supplementation during pregnancy. PMID- 7870325 TI - Cardiac rehabilitation in the Navy. AB - Cardiac rehabilitation has been effective in the management and recovery of the post-myocardial infarction population for almost 40 years. During that time, the fundamental components of rehabilitation have changed to reflect a growing complexity and number of cardiac patients. Great Lakes Naval Hospital has instituted a structured outpatient cardiac rehabilitation program. It is based on the needs of a large cardiac population with modifiable risk factors identified through quality improvement studies. Future implications and research in the area of cardiac rehabilitation include measurements of self-efficacy, long-term risk factor modification, cost effectiveness, gender-related differences, or morbidity and mortality. PMID- 7870326 TI - Subungual pigmented lesion caused by a bone spur: a mimic of a subungual melanoma. AB - Subungual pigmented lesions may be difficult to diagnose. A wide range of diseases present as pigmented lesions. The most concerning is subungual melanoma. A case is presented of a bone spur causing a subungual lesion mimicking melanoma. If subungual lesions do not show signs of resolution, timely biopsy is indicated. PMID- 7870327 TI - Can glucose-6-phosphate dehydrogenase deficiency be correlated with ABO blood type? AB - To determine if the presence of glucose-6-phosphate dehydrogenase deficiency (G6PDD) was correlated with a particular ABO blood type, results from a predeployment screening for G6PDD were categorized according to ABO blood type. The prevalence of G6PDD in blacks, Asians, and Mediterraneans (11.6%) mirrored that of other researchers. The most common blood type associated with G6PDD was O positive. Unlike those of other authors, this study did not disclose a statistically significant correlation (chi 2 = 11.354, df = 3, p < 0.01) between any one blood type and the presence of G6PDD. PMID- 7870328 TI - Combat injury with chronic osteomyelitis complicated by squamous cell carcinoma. AB - Penetrating injuries of the extremity are common in combat. The patient described in this paper sustained such an injury in Vietnam. He exhibited the frequent complication of chronic osteomyelitis and eventually the rare complication of squamous cell carcinoma. PMID- 7870329 TI - Physiological, emotional, and behavioral correlates of gender segregation. PMID- 7870330 TI - Peer relations and the development of competence in boys and girls. PMID- 7870331 TI - The emergence of gender segregation in toddler playgroups. PMID- 7870332 TI - Parent and adolescent expectancies: individual and relational significance. PMID- 7870333 TI - Does nitric oxide play a role in normal pregnancy and pregnancy-induced hypertension? PMID- 7870334 TI - Ischaemia and reperfusion injury in the kidney: current status and future direction. PMID- 7870335 TI - Of savoury and less than savoury salty matters. PMID- 7870336 TI - To stent or not to stent: is there a role for vascular endoprostheses in haemodialysis shunts? PMID- 7870337 TI - The loin pain haematuria syndrome. PMID- 7870338 TI - Hydrocarbons and glomerulonephritis--is the definite answer in? PMID- 7870339 TI - Renal biopsy--beyond histology and immunofluorescence. PMID- 7870340 TI - Intrarenal cytokine mRNA expression and location in normal and IgA nephropathy tissue: TGF alpha, TGF beta, IGF 1, IL-4 and IL-6. AB - Peptide regulatory factors (PRFs) are critical components in the regulation of glomerular inflammatory response to immune injury and may also have a primary role in modulating intrinsic cell proliferation and matrix synthesis. Dysregulation of PRFs and glomerular infiltration with inflammatory, including mononuclear, cells occur in models of nephritis, but direct evidence for their role is not established in normal and diseased tissue in man. Using in situ hybridization techniques capable of detecting specific cellular messenger RNA we have evaluated normal human and IgA nephropathy diseased renal tissue for expression and location of PRF encoding mRNA. Permeabilized tissue was examined by autoradiography using 35S labelled-antisense, and -sense riboprobes for TGF alpha, TGF beta, IGF 1, IL-4, and IL-6 encoding mRNA. TGF beta was constitutively expressed in normal glomerular mesangium, capillary loop, Bowman's capsule, and vascular endothelial and tubular cells, but was downregulated in IgA nephropathy tissue. In contrasting and distinct patterns, TGF alpha encoding mRNA was found in neither tissue, whereas IGF 1 mRNA was expressed in normal and also in diseased tissue. IGF 1 mRNA activity was intense within tubular cell cytoplasm in normals, with similar characteristics in IgA nephropathy. Cytokines IL-4 and IL-6 mRNAs were absent in normals, with IL-4 detectable throughout renal substance in disease; IL-6 gene transcription was intense in glomerular and vascular endothelial sites in IgA nephropathy. These findings implicate selective gene induction and suppression in disease, suggesting functional downregulation of glomerular TGF beta, coincident with autocrine functions for IL-6 and IL-4 in the pathogenesis of IgA-related nephropathy. PMID- 7870341 TI - Urinary excretion of cytokines and complement SC5b-9 in idiopathic membranous glomerulonephritis. AB - Idiopathic membranous glomerulonephritis (iMGN) has previously been shown to be associated with urinary excretion of terminal complement complexes while increased urinary levels of cytokines have been reported in mesangial proliferative glomerulonephritis. In the present cross-sectional study urinary excretion of IL-1 beta, TNF-alpha, IL-6, and soluble C5b-9 (SC5b-9) was examined for 23 patients with iMGN, 16 patients with diabetic nephropathy (DNP), and 17 healthy subjects. IL-1 beta excretion (pg/mg crea) was significantly higher in iMGN patients (375, range 162-11,000) than in DNP patients (39, range 22-59, P < 0.001) or healthy controls (151, range 23-481, P < 0.001). TNF-alpha excretion rate (pg/mg crea) was clearly higher (38, range 21-700) in iMGN patients than in DNP patients (14, range 8-52, P < 0.001) or healthy subjects (11, range 7-26, P < 0.001). Median IL-6 excretion (pg/mg crea) was only marginally higher in iMGN patients (73, range 0-850) than in healthy subjects (64, range 3-158, P = 0.02) but significantly higher than in DNP patients (29, range 17-47, P < 0.001). No significant correlation with corresponding serum values was observed for urinary IL-6 or TNF-alpha excretion. Urinary IL-1 beta and TNF-alpha correlated with decreased renal function. Five of 23 patients showed progression of iMGN over a follow-up of 6 months. The excretion of all cytokines, TNF-alpha in particular, was significantly higher in patients with a progressive disease than in the other patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870342 TI - Interleukin-6 production induced in peripheral blood mononuclear cells by a serum factor from IgA nephropathy patients is inhibited in vitro by specific sugars. AB - The basal production of IL-6 by cultured peripheral blood mononuclear cells (PBMC) from patients with IgAN, is markedly higher (A, 109 pg/ml) as compared to that of PBMC of either patients without clinical signs (I, 39 pg/ml) or appropriate controls (C, 44 pg/ml). When PBMC from healthy subjects were incubated in the presence of sera from patients A, the IL-6 production was strongly enhanced. No such an effect was observed by stimulating PBMC with sera from the other two groups of subjects (I, C). In another experiment we observed that the IL-6 production stimulated by serum from patients A could be inhibited by addition of specific monosaccharides. The inhibitory effect was rapidly abolished when the sugar-containing medium was substituted with the original one. Finally molecular components from serum of A were grossly separated by gel column chromatography. Individual fractions were incubated with PBMC of C: fractions with Mr > 30,000 highly stimulated the release of IL-6 (up to 1320 pg/ml); fractions with lower molecular weight were inactive. The data suggest the presence of an IL-6 releasing factor in the serum of IgAN patients. Although the chemical nature of such a factor is not yet established, the observations reported focus our attention to the lectins family. Since this factor seems potentially important in the understanding of the pathogenesis of IgAN, both its isolation and structural/functional characterization deserve further efforts. PMID- 7870343 TI - Molecular analysis of C3 allotypes in patients with systemic vasculitis. AB - The third component of complement (C3) exists in two main allotypic forms, C3S and C3F, distinguished at the DNA level by a single base change. An increased frequency of the rarer C3F allele has been reported in patients with the autoantibody nephritic factor and in several other autoimmune conditions such as rheumatoid arthritis and IgA nephropathy. Studies of the immunogenetic factors predisposing to the development of systemic vasculitis have produced conflicting results and no major genetic predisposing factors have been identified. We have studied the C3S/F polymorphism in 63 patients with systemic vasculitis using DNA allotyping by the amplification refractory mutation system, a modification of the polymerase chain reaction. The allele frequency in these patients was C3S 0.71, C3F 0.29 (expected C3S 0.8, C3F 0.19; chi-squared = 5.1, P < 0.025), with the average relative risk for the development of systemic vasculitis associated with the presence of a C3F allele being 2.6. Moreover, there was a marked excess of C3FF homozygotes (11/63, [17.5%], versus 4% expected: chi-squared = 9.5, p < 0.01). The average relative risk for the development of systemic vasculitis in C3F homozygotes was 5.1, indicating a gene dosage effect. These data indicate that the C3F allele is associated with a predisposition to the development of systemic vasculitis and that C3F homozygotes are at particularly high risk. This association is the strongest genetic factor reported so far for this group of diseases. PMID- 7870344 TI - Percutaneous renal biopsy: comparison of manual and automated puncture techniques with native and transplanted kidneys. AB - The diagnostic usefulness of the biopsy cylinder and biopsy-induced complications were investigated for 458 percutaneous renal biopsies (315 native, 143 transplant kidneys) on 339 patients (average age, 44.6 +/- 18.5 years) under two different biopsy regimes (regime I, manual biopsy technique with Tru-Cut needle, 14 gauge; regime Ii, automated biopsy technique using a Biopty instrument and adapted biopsy needle, 18 gauge). In 435 (95%) of the biopsies, kidney tissue with 9.09 +/- 5.28 glomeruli was obtained (regime I, 93.5%, 9.5 +/- 4.9 glomeruli; regime II, 96.5%, 8.7 +/- 5.6 glomeruli; P > 0.05). Neither with native nor with transplant kidneys was there any evident advantage for a particular regime in terms of the diagnostic usefulness of the cylinder. Bleeding complications (perirenal haematomas, bleeding into the renal pelvis, blood clots in the urinary bladder) were observed in 69 (15.1%) patients (regime I, 15.6%; regime II, 14.6%; P > 0.05). Clinically relevant bleeding complications were significantly rarer under regime II (9.1% versus 3.5%; P < 0.05). Complications were less frequent with transplant than with native kidneys (12.6% versus 16.2%). Doppler sonography of the biopsied transplant kidneys revealed arteriovenous fistulae in nine cases (6.3%; regime I, 8.0%; regime II, 5.4%). In general, use of an automated biopsy instrument and a thinner biopsy needle reduced the number of significant complications following percutaneous renal biopsy, while achieving comparably diagnostic efficacy. PMID- 7870345 TI - Relationship between hydrocarbon exposure and nephropathology in primary glomerulonephritis. AB - It has been proposed that renal tubular damage and chronic hydrocarbon exposure are causally related to progression of renal failure in primary glomerulonephritis. We examined the relationship between hydrocarbon exposure and morphological parameters of tubulointerstitial damage in 59 patients with biopsy proven primary glomerulonephritis (proliferative, n = 52; membranous, n = 7). From a mean follow-up period of 6 years patients were divided into two groups (GP) according to the presence or absence of progressive renal failure (GP 1, n = 24 with progressive renal failure) and (GP 2, n = 35 without progressive renal failure). The two groups were comparable in age, sex, duration of diagnosis (since the time of biopsy) and blood-pressure control. Patients were blindly assessed for chronic hydrocarbon exposure by a validated questionnaire. Biopsy cylinders were blindly assessed retrospectively for relative interstitial volume of the renal cortex by the point-counting method. In addition an assessment was made of the degree of fibrosis and chronic inflammatory cellular infiltrate. Hydrocarbon exposure score derived from the questionnaire until the time of renal biopsy correlated both with interstitial volume (r = 0.55; P < 0.001) and serum creatinine (r = 0.46; P < 0.001). Moreover, interstitial volume also correlated with serum creatinine (r = 0.63; P < 0.001). Chronic hydrocarbon exposure scores and relative interstitial volume in the renal cortex at the time of renal biopsy was significantly higher in GP 1 than GP 2 (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870346 TI - Lipoprotein abnormalities without hyperlipidaemia in moderate renal insufficiency. AB - To characterize lipoprotein metabolism during early renal insufficiency, plasma lipid and apolipoprotein profiles were determined in normotriglyceridaemic (NTG, n = 31) and hypertriglyceridaemic (HTG, n = 30) middle-aged patients with primary renal disease and with moderately impaired renal function (GFR 20-55 ml/min, mean: 37.2). Mean GFR was similar in the two patient groups. They were compared with 102 normolipidaemic control subjects. In comparison with controls the NTG patients (plasma triglycerides TG < or = 1.7 mmol/l, mean TG: 1.16 mmol/l) had significantly increased plasma concentrations of apo C-III and apoB. The apoA-I levels tended to be lower and as a consequence the apoA-I/apoC-III ratio, considered to represent the hallmark of the altered apolipoprotein profile in renal dyslipoproteinaemia, was markedly lower in NTG patients (8.7 versus 16.8, P < 0.001). There was also a reduction of the antiatherogenic ratio apoA-I/apoB and an increase of the apoC-III/apoE ratio. The HTG patients (mean TG: 3.22 mmol/l) showed the same, but even more accentuated, qualitative changes as the NTG patients. There was a fourfold increase of apoC-III in VLDL-LDL lipoprotein fractions with little change in HDL in the HTG patients. In NTG patients the increase of apoC-III was found in VLDL-LDL and in HDL. Plasma insulin and PTH levels both correlated with the apoA-I/apoC-III ratio independently of GFR and BMI. This suggests a pathogenetic relationship between PTH-mediated alterations of insulin metabolism and the lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870347 TI - Parathyroid hormone is not an inhibitor of lipoprotein lipase activity. AB - The reduced lipoprotein lipase (LPL) activities in uraemia are reflected by increased serum triglyceride concentrations and reduced HDL cholesterol concentrations. Both hyperparathyroidism and circulating inhibitor(s) of LPL have been associated with the disturbances of lipid metabolism in uraemia. The aim of the present study was to investigate if parathyroid hormone (PTH) had an inhibitory effect on LPL activity. Plasma post-heparin LPL activities, plasma LPL inhibitory activities, serum PTHintact and serum PTHC-terminal concentrations were analysed in 20 patients on haemodialysis and 20 healthy controls. The effects of purified, human PTHintact and a carboxyterminal fragment of PTH (PTH39 84) on LPL activities in post-heparin plasma from healthy individuals and on the enzyme activity of purified, bovine milk LPL, activated with apolipoprotein CII, were studied. Patients had significantly higher plasma LPL inhibitory activities than controls, but there was no correlation between plasma LPL inhibitory activities and serum PTH concentrations. Neither PTHintact nor PTH39-84 had a significant effect on LPL activities in vitro. Thus there was no evidence of a direct inhibition of LPL activity by PTH under the present in-vivo or in-vitro conditions. PMID- 7870348 TI - Effect of dietary protein restriction on the progression of renal failure: a prospective randomized trial. AB - One hundred twenty-eight patients with different renal diseases and chronic renal failure, stratified according to the underlying disease, were enrolled in a randomized controlled trial to investigate the effects on the rate of decline of renal function of two diets, a controlled protein diet (CPD) of 1 g protein/kg ideal body-weight (i.b.w.)/day, and a low-protein diet (LPD) of 0.6 g protein/kg i.b.w./day, given for 27.1 +/- 21.8 months. Dietary compliance was assessed by a dietary questionnaire, dietary interviews and measurement of 24-h urinary urea excretion. At the end of 6 months, actual mean protein intake was higher than expected (1.06 +/- 0.25 g/kg i.b.w./day) in CPD patients, and (0.80 +/- 0.21 g/kg i.b.w./day) in LPD patients: values were similar at 12 and 18 months after the time of enrollment. The end-point, defined as halving of creatinine clearance, was reached in 40% of patients on CPD, and in 28.6% of those on LPD (P = 0.038 by comparative life-table analysis). Multivariate regression analysis confirmed that CPD was associated with a higher risk of progression than LPD, and that two additional parameters (creatinine clearance at the time of randomization and average proteinuria during the follow-up) were significant independent risk factors, even more important than protein intake. PMID- 7870349 TI - Calcitriol and calcium carbonate therapy in early chronic renal failure. AB - The aim of this study was to evaluate the effects of a combined low-dose therapy of calcitriol and calcium carbonate on bone metabolism in the early phases of chronic renal failure. A 30-month study involving 17 patients with ECRF was made: 6 months of observation were followed by 24 months of therapy (calcitriol 0.25 microgram/day plus calcium carbonate 1 g/day). The most important results were that renal function was stable throughout the study and there was an increase in calcaemia and a decrease in plasma alkaline phosphatase, plasma osteocalcin, plasma PTH and urinary hydroxyproline. We observed a progressive slowing of the rate of loss of appendicular bone density as well as a decrease of osteoblastic and osteoclastic activity and an improvement of bone mineralization. In conclusion, low doses of calcitriol plus calcium carbonate seem to improve the biochemical and bone derangements in early renal failure. PMID- 7870350 TI - Uraemic muscle metabolism at rest and during exercise. AB - The effect of chronic renal failure and the accompanying hyperphosphataemia on muscle metabolism at rest and during exercise was examined in a group of undialysed patients suffering from chronic renal failure. 31P magnetic resonance spectroscopy was used to measure intracellular high-energy phosphates in resting muscle as well as changes in the concentrations of these metabolites during exercise and recovery from exercise. In resting muscle, cell [Pi] rose with plasma [Pi], and free [ADP] changed such that the phosphorylation potential ([ATP]/([ADP] x [Pi])), which probably controls mitochondrial oxidation in resting muscle, was preserved despite a wide variation in cell [Pi]. The maximal oxidative capacity of the muscle was calculated from the kinetics of phosphocreatine recovery after exercise. There was no reduction in uraemic muscle oxidative capacity compared to control muscle. This contrasts with our finding of a reduction in the mitochondrial oxidative capacity in the muscle of patients established on dialysis, suggesting that a substance crucial for mitochondrial function or substrate supply to mitochondria is removed by dialysis. PMID- 7870351 TI - Diurnal blood-pressure variations in haemodialysis and CAPD patients. AB - The influence of variations in fluid state on diurnal blood pressure was studied by measuring day-time and night-time blood pressure during a 3-day interdialytic period in 10 normotensive and 10 hypertensive haemodialysis patients using Spacelab 90207 Monitors. Ambulatory blood pressure was also measured during 24 h in 11 normotensive and nine hypertensive CAPD patients, and in nine normotensive and 11 hypertensive control patients with a normal renal function. Antihypertensive drugs had been discontinued for at least 3 weeks before the study period. Optimal dry weight in the haemodialysis patients was estimated by echography of the inferior vena cava and in the CAPD patients on clinical grounds. Although in the dialysis patients and controls a significant nocturnal blood pressure reduction was found, day-night blood pressure difference in the dialysis patients was blunted when compared with the control patients. No significant differences in diurnal blood pressure variation was found between the normotensive and the hypertensive patients. Day-night blood pressure differences in the haemodialysis patients did not change during the 3-day interdialytic period. Also the more stable fluid state of the CAPD patients was not associated with significant different diurnal blood pressure variation compared to the haemodialysis patients. We conclude that factors other than changes in extracellular fluid volume are responsible for a blunted day-night difference in blood pressure in dialysis patients. PMID- 7870352 TI - Renal handling of prednisolone/prednisone: effect of steroid dose and 11 beta hydroxysteroid dehydrogenase. AB - The purposes of this study were: (1) to determine under steady-state conditions whether the renal clearance of prednisolone is concentration dependent, and (2) to establish whether the urinary excretion of prednisolone and its biologically inactive 11-dehydro metabolite prednisone depend upon the activity of 11 beta hydroxysteroid dehydrogenase (11 beta-OHSD). For that purpose 10 healthy volunteers were infused to steady state over a 13-h period either at a low (11 micrograms/h x kg) or a high (70 micrograms/h x kg) rate with prednisolone on two occasions, once without and once with administration of glycyrrhetinic acid, an inhibitor of 11 beta-OHSD. Prednisolone and prednisone were measured by high pressure liquid chromatography. Mean renal clearance values of total or unbound prednisolone were several times higher during the high than the low infusion rate. The fractional renal clearance of unbound prednisolone during the high, but not during the low infusion rate exceeded 1. This indicates that in addition to unbound prednisolone, protein-bound prednisolone is excreted in urine at high plasma concentrations. Inhibition of 11 beta-OHSD increased the urinary ratios of prednisolone/prednisone in all subjects. CONCLUSIONS: (1) The renal clearance of prednisolone is concentration dependent; (2) there must be tubular secretion and/or glomerular filtration of prednisolone bound to plasma proteins; (3) the urinary excretion of prednisolone/prednisone is modulated by the activity of 11 beta-OHSD. PMID- 7870353 TI - Effects of cyclosporin A withdrawal on renal function and renal stimulation in liver transplant patients treated with triple-drug immunosuppression for over 2 years. AB - The influence of CsA withdrawal on the glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) was prospectively studied in nine stable liver transplant recipients. Before CsA withdrawal (test 1), and 6 months thereafter (test 2) the renal function was determined by measuring GFR and the ERPF with 125I-iothalamate and 131I-hippuran respectively. The renal function was also stimulated with dopamine, with an amino-acid infusion and a combination of both. After CsA withdrawal the GFR increased, median from 74 ml min-1 to 90 ml min-1, (P < 0.04). The ERPF also increased, median from 310 ml min-1 to 380 ml min-1, (P < 0.03). In test 1 as well as in test 2 the renal function could be stimulated, especially with dopamine. GFR and ERPF improved, even after more than 2 years of CsA treatment. These results suggest that long-term CsA treatment impairs the renal function, though in these liver transplant patients CsA treatment did not prevent afferent and efferent arteriolar vasodilatation after renal stimulation. This reversible intrarenal vasoconstriction during CsA treatment may predict renal improvement after CsA withdrawal. PMID- 7870354 TI - Renal arteriovenous shunting in rejecting allograft, hydronephrosis, or haemorrhagic hypotension in the rat. AB - We studied the occurrence of arteriovenous (A-V) shunting in three experimental rat models, namely in rejecting allograft kidney, in uni- or bilateral ureteral obstruction, and in haemorrhagic hypotension. Isografted or sham-operated rats served as controls. Radiolabelled microspheres were injected into the renal artery and the increase in the amount of radioactivity in the lungs was considered to reflect A-V shunting in the kidney. In animals exposed to haemorrhage, with a blood pressure not less than 70% of the initial blood pressure, practically no shunting was seen. When animals were bled to a hypotension beyond the autoregulation, A-V shunting occurred inversely correlated to the degree of hypotension. In ureteral obstruction, a less marked but significant increase in shunting of microspheres to the lungs was found after 24 h of unilateral obstruction, irrespective of whether the spheres were injected into the obstructed or the contralateral kidney. Significant A-V shunting during the allograft rejection process was also demonstrated. Histologically, microspheres were found in afferent arterioles less frequently in kidneys with A V shunting than in controls. These results indicate that A-V shunting is involved in haemorrhagic hypotension, renal graft rejection, and hydronephrosis. In the latter situation A-V shunting is probably regulated by a humoral factor. PMID- 7870355 TI - Bilateral nephrectomy and haemodialysis for the treatment of severe loin pain haematuria syndrome. PMID- 7870356 TI - Schonlein-Henoch glomerulonephritis complicating diabetic glomerulosclerosis. PMID- 7870357 TI - Resistance to recombinant human erythropoietin therapy in a child with renal failure due to primary hyperoxaluria type 1. PMID- 7870358 TI - Granulomatous sarcoid nephritis presenting as frank haematuria. PMID- 7870359 TI - An infected right atrial thrombus--a new complication of haemodialysis associated subclavian vein catheterisation. PMID- 7870360 TI - Fatal cyclophosphamide-induced interstitial pneumonitis in a renal transplant patient. PMID- 7870361 TI - Intraperitoneal fluconazole therapy for Trichosporon cutaneum peritonitis in continuous ambulatory peritoneal dialysis. PMID- 7870362 TI - Second International Symposium on Lipids, Atherosclerosis and the Kidney: summary of scientific presentations. PMID- 7870363 TI - Visual deterioration in a patient with hydronephrosis. PMID- 7870364 TI - Klaus Hierholzer, recipient of the Franz Volhard Medal. PMID- 7870365 TI - Spontaneous release of interleukin-8 by glomerular macrophages from patients with rapidly progressive crescentic glomerulonephritis. PMID- 7870366 TI - Renal vein ammonia concentration in unilateral renal artery stenosis and hypertension. PMID- 7870367 TI - Does hyperprolactinaemia predispose to aluminium toxicity in chronic renal failure? PMID- 7870368 TI - ACE inhibitors in the management of haemodialysis ascites. PMID- 7870369 TI - Resistance to rHuEpo and kidney graft rejection. PMID- 7870370 TI - Responsiveness to erythropoietin and intrinsic inflammatory status in haemodialysis. PMID- 7870371 TI - Does diurnal variation in blood pressure exist in CAPD patients? PMID- 7870372 TI - Arterial endothelialitis in chronic renal allograft rejection. PMID- 7870373 TI - Therapeutic interventions for child victims of violence. AB - Victims and perpetrators of violence often are children caught in a cycle of fear, anger, and hopelessness. The aftermath of violence often is more traumatic and disruptive to victims than the original traumas. Treatment involves a multidimensional approach to the past, present, and future. PMID- 7870374 TI - School intervention programs: an approach to preventing child abuse. AB - Child abuse and neglect are often a child's first introduction to the violent society in which he lives. Combatting violence, including child abuse, requires a multifaceted approach to reinforce the value of a human life and the commitment to a nonviolent lifestyle. Combining a home, school, and community approach strengthens a community's ability to improve skills of parents, teachers, youth, and citizens. EPIC program is such an approach that can be tailored to meet local needs. It is available in 50 New Jersey communities with replication assistance provided by NJ-NCPCA. PMID- 7870375 TI - Geriatric assessment in the diagnosis and treatment of elder abuse. AB - With the growing problem of elder abuse, it is imperative that physicians become aware of the warning signs of elder abuse. In addition, physicians must be knowledgeable in the diagnosis and treatment of elder abuse. Educated physicians can help to alleviate this problem. PMID- 7870377 TI - AIDS. BME guidelines. PMID- 7870376 TI - MSNJ initiatives in the campaign on domestic violence. AB - Reflecting concern of the Medical Society of New Jersey, the Subcommittee on Violence is dealing with legislative initiatives, physician education, and the development of innovative strategies concerning violence. The Subcommittee is studying the physician's role in the diagnosis and treatment of violence. PMID- 7870378 TI - Discharge for refusing to treat HIV patients. PMID- 7870379 TI - Legal resources in confronting violence in New Jersey. AB - The Prevention of Domestic Violence Act protects victims from a multitude of violent acts including harassment and stalking. The Act covers the procedure for filing a complaint, the factors to be considered by the court, and the relief available for residents of New Jersey. PMID- 7870380 TI - Medical partnerships with community-based organizations in violence prevention. AB - Youth violence is an important public health issue. The magnitude of youth violence in New Jersey is defined along with innovative community projects. The authors present recommendations for health professionals involved in youth violence behavior. PMID- 7870381 TI - Exocytosis relating proteins in the nervous system. AB - Hypothetical models of the molecular mechanism underlying presynaptic exocytosis were reviewed and the exocytosis relating proteins were categorized into four groups: docking, anchoring, fusion and inhibiting proteins. HPC-1/syntaxin, an axonal membrane protein, was classified as an anchoring protein, not as the vesicle docking protein, because electron microscopic study using cryoimmunogold technique revealed that HPC-1 distributed over the entire axonal membrane, where the synaptic vesicles were not 'docked' to the membrane. Since selective toxin or antibody against HPC-1 affected exocytosis, HPC-1 might be a necessary component for the exocytosis, but HPC-1 by itself seemed to have no ability to bind synaptic vesicles to the membrane in vivo. The molecular mechanism for Ca dependent, rapid exocytosis and possible roles of the exocytosis relating proteins in the neurite morphogenesis are discussed. PMID- 7870382 TI - Photoreceptor light-adaptation mediated by S-modulin, a member of a possible regulatory protein family of protein phosphorylation in signal transduction. AB - In vertebrate retinal photoreceptors, cytoplasmic [Ca2+] decreases upon exposure to light. A Ca(2+)-binding protein, S-modulin, detects this [Ca2+] decrease and reduces the light-sensitivity of the cell to induce light-adaptation. The reduction of the sensitivity is attained by disinhibition or facilitation of rhodopsin phosphorylation, a quenching mechanism of light-activated rhodopsin. S modulin-like proteins are found in the brain as well. Several of these proteins show similar S-modulin effects, suggesting that these proteins also participate in the regulation of protein phosphorylation in the signal transduction in their host cells. PMID- 7870383 TI - Automated collection of conditioned medium from organotypically cultured brain slice. AB - For the analysis of neural activity over a long period of time, the organotypic culture of mammalian brain slices provides excellent specimens. To effectively utilize the slice culture, we developed a device for automatic sampling of the culture medium. This device is a computer-controlled combination of a multichannel peristaltic pump to remove the media from the glass culture containers, a fraction collector designed to allow quick freezing of the samples, and a multichannel syringe pump to deliver new media to the containers. Using this device, substances released as results of neural activities can be collected at regular intervals over several days. We monitored the circadian release of arginine-vasopressin from cultured suprachiasmatic nuclei. We also monitored tonic releases of lactate dehydrogenase from cultured hippocampi phasically treated with an excitotoxin and from those transiently deprived of oxygen/glucose. PMID- 7870384 TI - Regional cerebral blood flow in the frontal, parietal and occipital cortices increases independently of systemic arterial pressure during slow walking in conscious rats. AB - Regional cerebral blood flow (rCBF) in the frontal, parietal and occipital cortices was measured using laser Doppler flowmetry during walking in conscious rats at moderate speed on a treadmill (4 cm/s) for a 30 s period. During walking rCBF increased in all these three cortices. The rCBF in the parietal cortex started to increase within a few seconds after the start of walking, and continued to increase 42 +/- 16% (mean +/- S.D.) until the end of walking. Within 90 s after walking had ceased, the increased rCBF returned to pre-walking basal levels. The rCBF responses in the frontal and occipital cortices were identical to that in the parietal cortex. Mean arterial pressure (MAP) in a caudal artery of the tail during walking was increased by about 10%. Injection of atropine (5 mg/kg, i.p.), a muscarinic cholinergic receptor antagonist that permeates the blood brain barrier (BBB), reduced the walking-induced increase in cortical rCBF, as determined by measurement of parietal rCBF, from 42 +/- 12% to 28 +/- 15%. However, injection of methylatropine (5 mg/kg, i.p.), a muscarinic cholinergic receptor antagonist that does not permeate the BBB, did not affect the response of rCBF. Neither drug affected the walking-induced response of MAP. Injection of mecamylamine (20 mg/kg, s.c.), a nicotinic cholinergic receptor antagonist that permeates the BBB, reduced the walking-induced increase in cortical rCBF from 47 +/- 12% to 30 +/- 12%. Injection of hexamethonium (20 mg/kg, s.c.), a nicotinic cholinergic receptor antagonist that does not permeate the BBB, did not affect the responses of rCBF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870385 TI - Augmenting action of nicotine on population spikes in the dentate gyrus of the guinea pig. AB - Effects of nicotinic cholinergic agents on field potentials recorded from the dentate gyrus were studied in thin transverse sections of the hippocampus of the guinea pig. Nicotine augmented the population spike elicited by the second stimulus of a paired stimulation to the molecular layer. The threshold concentration of nicotine to cause this effect was 5-10 microM. The augmentation of the spike was not accompanied by an increase in the rising slope of population excitatory postsynaptic potentials, and was not observed in the presence of bicuculline. Carbamylcholine had a weak and inconsistent effect. D-tubocurarine and mecamylamine also augmented the population spike. The action of nicotine was blocked by hexamethonium. These results suggest that nicotine facilitates the generation of action potentials in granule cells by depressing inhibitory processes, and that properties of nicotinic cholinergic receptors are different in different subfields of the hippocampal formation, presumably reflecting the diversity of the receptors. PMID- 7870386 TI - Long-term potentiation and depression in the dentate gyrus, and effects of nicotine. AB - Effects of a brief high-frequency stimulation or a prolonged low-frequency stimulation in the presence and absence of nicotine were studied in thin transverse slices of the dentate gyrus prepared from the guinea pig. Test and conditioning stimulations were delivered to the middle one-third of the molecular layer, and the slope of the population excitatory postsynaptic potentials (EPSPs) elicited by the test stimulation was taken as an indicator of potentiation or depression. Nicotine was without effects on the N-methyl-D-aspartate (NMDA) component of EPSPs at 50 or 100 microM. A brief high-frequency stimulation induced long-term potentiation (LTP) in the presence of bicuculline. Nicotine (50 microM) almost doubled the magnitude of LTP. In the absence of bicuculline, an identical high-frequency stimulation induced a brief depression, the duration and magnitude of which were increased by nicotine. The increase was not statistically significant, however. In contrast to observations in the region CA1, 720 pulses at 1 Hz delivered after induction of LTP failed to induce long-term depression. Nicotine did not modify the after-effect of the low-frequency stimulation. It was discussed that the facilitation of LTP by nicotine probably resulted from suppression of inhibitory processes. PMID- 7870387 TI - Transduction steps which characterize retinal cone current responses to flash stimuli. AB - There are three prominent characteristics in current responses of retinal cones to flash stimuli when compared with those of rods. First, the time-to-peak of the photocurrent is two to four times faster than for the rod. Second, the photosensitivity of the cone is more than one order of magnitude lower than that of the rod. Third, current responses of cones resemble characteristic under-shoot in the recovery phase. At present, however, it is not known what kinds of mechanisms underlie these characteristics. In the present study, critical steps which characterize cone responses have been investigated by changing rate constants in the model for the signal transduction scheme of cone outer segments under the assumption that the scheme is basically the same as for rods. The computer simulations have shown that rate constants were divided into three categories: those which do not appreciably change photocurrent, those which change only photosensitivity, and those which change both sensitivity and speed. Furthermore, rate constants which characterize undershoot were identified. From these simulations it has been revealed that characteristics of the cone response could be reproduced by changing the rate constants. The critical ones are rate of rhodopsin deactivation, rate of GTP hydrolysis, and deactivation rate of activated phosphodiesterase. These results suggest possibilities that the signal transduction mechanisms in cones are basically the same as those for rods, while rate constants are different. PMID- 7870389 TI - 18th Annual meeting of the Japan Neuroscience Society. Tokyo, Japan, December 6 8, 1994. Abstracts. PMID- 7870388 TI - Effects of a carrageenan-induced inflammation in rabbit lumbar facet joint capsule and adjacent tissues. AB - The effects of experimentally induced inflammation of the lumbar facet joint capsule and adjacent tissues were investigated electrophysiologically and histologically. Type II carrageenan was injected into the receptive fields innervated by identified mechanosensitive afferent units. The multi-unit spontaneous background discharge rate showed increases that consisted of two phases over a time period of 150 min: the first phase (0-30 min) and the second phase (45-150 min). The time course of single units, identified as groups II, III and IV, and silent units, was also investigated. The silent unit discharge rates displayed a gradual increase in the first 15 min and persisted beyond 75 min. Histological examination revealed inflammatory changes in carrageenan injected tissues. In contrast, in isotonic saline injected control experiments there were no changes observed in the electrophysiological or histological studies. This study shows the effects of inflammation in rabbit lumbar facet joint capsule and adjacent tissues. The electrophysiological results show that inflammation of the facet joint and deep back muscles causes (1) increases in multi-unit discharge rate, (2) sensitization to mechanical stimuli and (3) recruitment of previously silent units. Inflammatory changes were also demonstrated histologically. PMID- 7870390 TI - Filter choice for reconstruction tomography. PMID- 7870391 TI - Absence of residual effects after physiological stimulation of the visual and motor cortex: an [15O]-H2O PET study in humans. AB - Cognitive experiments using positron emission tomography (PET) with [15O]-H2O require multiple scans done at 10 to 12 min intervals. Momose and colleagues reported that regional cerebral blood flow changes in response to visual stimulation do not return to baseline even 15 min after the stimulation. If confirmed, this fact would have important implications for the design and interpretation of PET cognitive studies. The purpose of this study was to determine the temporal course of residual effects following visual and motor stimulation. Six healthy volunteers undertook six scans each. Two scans were done to establish a baseline, one to observe the task induced activation, and three scans to investigate the residual effects at varying intervals after the task. The data were analysed using both statistical parametric mapping and a region of interest analysis. The visual and motor task produced robust activations bilaterally in the occipital cortex and in the contralateral primary motor cortex. There was no evidence for a statistically significant residue effect at any of the three intervals studied (30 s, 3 and 6 min). Our results refute the findings of Momose and colleagues and suggest that the 10-min interscan interval is more than adequate to re-establish a resting baseline. PMID- 7870392 TI - Structural modifications of monoclonal antibodies following direct versus indirect labelling with 99Tcm: does fragmentation really occur? AB - In this study, the influence of direct and indirect 99Tcm-labelling on the molecular structural integrity of monoclonal antibodies and other immunoglobulin preparations was investigated. Molecular composition of antibody preparations [two IgG monoclonal antibodies, one F(ab')2 fragment (all directly labelled), one indirectly labelled polyclonal human immunoglobulin preparation] and of serum samples after antibody injection were studied using polyacrylamide gel electrophoresis (PAGE; non-reducing and reducing conditions) and gel filtration chromatography. With PAGE, depending on the conditions used, a variety of lower molecular weight products could be detected. When analysing the same antibody preparations by gel filtration chromatography, all complete antibody preparations appeared as homogenous proteins of IgG molecular weight (150 kD). In F(ab')2 fragments, some further fragmentation to Fab' was noticed. Neither in vitro nor in vivo (serum) evidence of smaller fragments could be detected by gel filtration, despite their presence in PAGE. We therefore conclude that through the reductive step of direct 99Tcm-labelling, interchain disulphide linkages are broken but the polypeptide chains of complete IgG remain associated by non covalent linkages, whereas (F(ab')2 is fragmented further to form essentially Fab'. The protein-denaturating conditions of PAGE (even if performed non reducingly) seem to produce artifacts, not representing the real in vivo condition. PAGE results should therefore be interpreted only with great care. PMID- 7870393 TI - Measurement of organ volume by single photon emission computed tomography. AB - The aim of this study was to develop a new algorithm for volume determination by single photon emission computed tomography (SPECT). Different algorithms were evaluated through phantom studies. The results show that the algorithm combining moment-preserving bilevel thresholding and best-fit Laplacian second derivative edge detection can provide the most accurate measurement of volume. Besides, this method can be utilized in different SPECT systems with no need for further phantom studies. In patient studies, the results of liver volume calculation have indicated that this is a useful technique in clinical medicine. PMID- 7870394 TI - 99Tcm-cystine, a renal function and imaging agent: a comparative study in dog with 131I-hippurate and 99Tcm-glucoheptonate to evaluate its functional and imaging characteristics. AB - 99Tcm-cystine, which has been proposed as a renal radiopharmaceutical for evaluating renal morphology and function in a single experiment, is compared with 131I-orthoiodohippurate (OIH) with respect to its renal clearance and extraction parameters and with 99Tcm-glucoheptonate (GHA) regarding its imaging characteristics. In spite of its comparable renal accumulation with 131I-OIH, its clearance (10.1 +/- 1.0 ml min-1 kg-1) was lower than that of 131I-OIH (21.5 +/- 0.9 ml min-1 kg-1) but was higher than that of 125I-iothalamate (5.4 +/- 0.6 ml min-1 kg-1). Extraction efficiencies of 99Tcm-cystine, 131I-OIH and 125I iothalamate were 39 +/- 5, 64 +/- 4 and 27 +/- 3, respectively. The glomerular filtration components of 99Tcm-cystine and 131I-OIH were 26 and 16% of their respective clearances. In probenecid-treated animals the clearance of both agents was affected to a similar extent and fell to half of their respective control values, whereas tubular secretory components were found to be 19 and 31% of the controls. The kidney images obtained with 99Tcm-cystine were superior to those obtained with 99Tcm-GHA at different time points. Therefore, considering both renal function and imaging properties of 99Tcm-cystine it appears that this radiopharmaceutical offers some definite advantages over the currently available renal agents and commands further study. PMID- 7870395 TI - Quality assurance of radiopharmaceuticals. Radiopharmacy and Quality Control Pharmacists Subcommittees of the Regional Pharmaceutical Officers Committee. AB - This paper describes a level of quality assurance deemed to be acceptable for the preparation of radiopharmaceuticals within hospitals in the UK. It is not intended to give detailed methodology or guidance on premises or procedures, but to give general guidance which can be tailored to meet local needs. It is hoped that a high standard of radiopharmaceutical preparation will be maintained nationwide. PMID- 7870396 TI - A mechanism for professional and organizational audit of radiopharmacy departments. AB - An audit document is presented which can be used to assess the radiopharmacy service in a particular institute. It can be used for self-assessment or can form the basis for peer review. The document covers a wide range of aspects of radiopharmacy. It is acknowledged that the document will need constant review and where appropriate, modification, in order to reflect changes in practice or legislation. PMID- 7870397 TI - Efficacy of quantitative cholescintigraphy in the diagnosis of sphincter of Oddi dysfunction. AB - The diagnostic efficacy of time-activity curves (TAC) and common bile duct dynamics (CBDD) derived from quantitative cholescintigraphy (QC) was assessed in patients with suspected sphincter of Oddi dysfunction (SOD). Quantitative cholescintigraphy was performed on 34 cholecystectomized individuals with suspected SOD and 26 asymptomatic controls. Each patient with suspected SOD underwent endoscopic retrograde cholangiography and sphincter of Oddi manometry (SOM). After exclusion of eight patients because of failure of manometry, the final diagnoses of the remaining 26 patients were taken as the gold standard by which to determine the detectability of TAC and CBDD. The sensitivity of TAC reached 68.8%. Common bile duct dynamics showed equal sensitivity but was more specific than TAC. The sensitivity improved to 87.5% when TAC and CBDD were combined. We conclude that non-invasive QC provides good sensitivity and specificity in evaluating cholecystectomized patients with suspected SOD. PMID- 7870398 TI - 99Tcm-MIBI uptake in green plants. AB - Uptake of 99mTcm-sestamibi by biological structures depends on delivery and concentration by electrochemical gradients through the biological membranes and can be simply studied using a green plant model in which photosynthesis tightly modulates water and solute regional flow. Photosynthesis creates electrochemical gradients inside chloroplasts and mitochondria. Moreover, it is the driving force for the movement of water and solutes through induction of pore opening which causes capture of CO2 and loss of water vapour. Thus osmotic pressure increases thereby drawing water from the roots. Hypoestes sanguinolenta was used as an experimental model. This plant displays green zones (with several chloroplasts) and red zones (where they are absent). To detect the uptake differences between these zones we used a new, high-resolution gamma camera. Our results show that (a) 99mTcm-sestamibi is actively transported with water and ions by xylem to leaves where it may diffuse at cellular levels; (b) activation of photosynthesis by light strongly influences the total uptake and the selective compartmentation in green zones; and (c) the green plant's particular physiology tremendously enhances the differences between 99Tcm-sestamibi and 201Tl uptake. We suggest that viable cells, able to create and maintain electrochemical gradients, selectively take up 99Tcm-sestamibi. PMID- 7870400 TI - The effects of informational intervention on state anxiety and satisfaction in patients undergoing bone scan. AB - The aim of the study was to identify the most beneficial mode, in terms of anxiety reduction, of giving patients information prior to them undergoing a bone scan. (Research has identified the scan procedure as having a demonstrative effect on anxiety.) Additionally, satisfaction with the adequacy of the information was examined. On the day of the scan two experimental groups received either written or verbal information, the control group receiving no additional information (all had received the standard letter). All groups completed both the Spielberger's State Anxiety and a satisfaction questionnaire. Anxiety data were analysed by analysis of variance and the Duncan's test, whilst satisfaction was examined in terms of percentages. A significant difference at the 0.029 level was found in terms of anxiety reduction between both the experimental groups compared to the control group. No significant differences were found between the two experimental groups. Findings with regard to satisfaction with the adequacy of the information given showed that 78.6% of the subjects in the experimental group who received verbal information were satisfied compared to 71.4% in the group who received written information and 28.6% in the control group. PMID- 7870399 TI - Normal data for lumbar spine bone mineral content in healthy elderly Chinese: influences of sex, age, obesity and ethnicity. AB - Bone mineral density (BMD) at the level of the lumbar spines (L2-L4) was determined in 353 normal, elderly Chinese (248 females and 95 males, aged 40-85 years) living in Taiwan with a commercial dual-photon absorptiometer (DPA) and presented as g cm-2. The body mass index (BMI) was calculated according to the standard formula, and if the BMI was > 25 kg m-2 the patient was considered as being obese. The results show that linear correlations between the age and BMD for males or females are significant. Regular decreases of BMD values in the different age groups are found for both sexes. In addition, the BMD values of males are higher than those of females. The obese group was significantly higher than the lean one with regard to BMD for males and females including premenopausal and postmenopausal groups. In comparison with the normal data of American residents, the mean BMD of Chinese are lower than those of American residents of the same ages. Our findings indicate that the influence of sex, age, obesity and ethnicity exist in the BMD values of elderly healthy Chinese. PMID- 7870402 TI - Film-based fabrics. PMID- 7870401 TI - Lung inflammation in patients with systemic lupus erythematosus detected by quantitative 67Ga-citrate lung scanning. AB - The severity of lung inflammation in 34 patients with systemic lupus erythematosus (SLE) was measured by quantitative 67Ga-citrate lung scanning. The severity of lung inflammation in SLE was represented by the 67Ga uptake index (GUI). Quantitative 67Ga lung scanning was also performed on 20 normal controls for comparison with the SLE patients. The patients were divided into two subgroups according to the following two criteria: (a) stable or flare stage according to clinical features; or (b) positive or negative results of chest X ray. The GUI values of the subgroups were also compared. The results revealed a trend towards higher values of GUI in SLE patients than in the normal controls. The GUI values were also higher for SLE cases with a flare stage or a negative chest X-ray than in SLE cases with a stable stage or a positive chest X-ray. The statistical results reveal that the differences in the GUI values are not significant. However, we found that (1) positive chest X-ray findings may be a later manifestation of a lung inflammation and (2) the values of GUI parallel clinical features in SLE patients. PMID- 7870403 TI - AT&T Bell Lab's ergonomic program aims to cure VDT workstation ills. PMID- 7870404 TI - New approach set to protect workers from asbestos exposures below PELs. PMID- 7870405 TI - Getting them back to work safely. PMID- 7870406 TI - Laser-based communication systems emit radiation, an eye hazard. PMID- 7870407 TI - Academy '94. American Academy of Optometry. San Diego, California, December 9-13, 1994. Abstracts. PMID- 7870408 TI - [Reproductive health at the threshold of the third millennium]. AB - Attention is called to the extent and consequences of uncontrolled population growth. The concept of reproductive health is defined and the most important pillars are presented. These are the status of women, family planning, antenatal care, decreasing maternal mortality, termination of pregnancy, sexually transmitted diseases (AIDS), infertility, malignancies of the reproductive tract, nutrition, care of the newborn and children, adolescent sex, dangerous sexual practices, way of life and environment. The contradiction of increasing health costs and increasing poverty is exposed. PMID- 7870409 TI - [Plastic surgery in the context of surgery for breast cancer. Breast reconstruction using the patient's own tissue]. AB - The breast reconstructions after mastectomies are overviewed. The criteria of a successful operation are discussed. The result of breast reconstruction with latissimus dorsi and rectus abdominis musculocutaneous flaps are presented. The spectrum of 106 breast reconstructions of from 1987 to 1993 is published. The methods of adequate reconstructions mall, middle size and large breasts are discussed. With the reconstruction of large breasts the best results have been achieved by the transfer of rectus abdominis musculocutaneous flap with micro vascular anastomoses. This flap has the best blood supply and this procedure causes the less damage to the donor area. It is stated that the breast reconstructions with living tissues are superior and preferable. PMID- 7870410 TI - [A new thrombocyte aggregation-inhibiting and fibrinolysis-promoting synthetic molecule: RGDF (Arg-Gly-Asp-Phe) coupled with the carboxyterminal antiplasmin peptide]. AB - OBJECTIVE: Synthesize such hybrid peptides, which contain the RGD (Arg-Gly-Asp) sequence coupled with another peptide containing lysine residues in special positions, to inhibit simultaneously platelet activation and promote fibrinolytic processes. DESIGN: The in vitro haemostasis modifying properties of the synthesized peptides were tested with ADP induced platelet aggregation, in vitro plasmin generation tests and fibrin-clot lysis assays. RESULTS AND CONCLUSIONS: RGDF (Arg-Gly-Asp-Phe) coupled with the carboxyterminal antiplasmin peptide (RGDFAP hybrid molecule) has a common concentration range for inhibiting platelet activation and increase plasmin generation along with accelerated in vitro fibrin clot lysis. PMID- 7870411 TI - [Adverse effects of combined use of acenocoumarol and acetylsalicylic acid after myocardial infarct and unstable angina]. AB - The authors examined the bleeding complications in 75 patients who received acenocoumarol and acetylsalicylic acid combined therapy. The studied population suffered from either acute myocardial infarction or unstable angina. Among the 75 patients in two cases (2.7%) appeared serious bleeding and in another 25 cases (33.3%) mild bleeding complications. There were no fatal cases. Comparing these data with literary data, the authors stated that in the study group the proportion of serious complications didn't increase in comparison with patients who received either acenocoumarol, warfarin or acetylsalicylic acid but mild bleeding appeared more frequently. This finding suggests that in high risk patients the combined acenocoumarol-acetylsalicylic acid therapy can be considered under strict control. PMID- 7870412 TI - [Hiatal hernia associated with mitral prolapse in childhood]. AB - Authors examined 17 cases of hiatal hernia, out of which 13 proved to have mitral valve prolapse. The diagnosis was based on auscultation, ECG and echocardiographic examination. The incidence of mitral valve prolapse (76.5%) found in this study in considerably high. Up to now no such relationship has been reported in the literature. At the moment it could not be stated that similar aetiological factors may play any role in the developmental of both hiatal hernia and mitral valve prolapse. At the same time it can not be excluded either, that the hiatal hernia and mitral valve prolapse are not a part of a connective tissue disorder. Authors plan to follow up the patients. PMID- 7870413 TI - [Repeated serious water intoxication in an aged patient. (Data on the relationship between the inappropriate antidiuretic hormone syndrome and the atrial natriuretic factor)]. AB - An old women was in an 8-year-period 9 times admitted to the hospital because of severe mental disturbances. The average serum sodium concentration was 126.25 +/- 2.43 mmol/l at the admissions; it increased to 139.44 +/- 1.40 mmol/l after intravenous infusion of hypertonic solutions accompanied with the disappearance of the mental disturbances. The patient was usually chronically hyponatremic due to the increased water intake and the insufficient water excretion. The latter was induced by the augmented vasopressin levels. The remarkable feature of the syndrome of inappropriate antidiuretic hormone secretion was its association with lowered blood level of atrial natriuretic factor accompanied by sodium, and volume depletion. Discontinuation of the exaggerated water intake resulted in the elimination of the permanent hyponatremia; no episode of water intoxication occurred during the last 3 and 1/2 years. PMID- 7870414 TI - [A forgotten ophthalmologist: Elemer Kocsis]. PMID- 7870415 TI - [Portraits of great physicians on coins]. PMID- 7870417 TI - [Comparative study of antibiotic use at hospital departments in 7 Hungarian hospitals 1989-1991]. AB - In their present work, authors, referring to their previous paper, wanted to compare the antibiotic consumption of the special medical fields in different hospitals. Computer database were utilised from different hospitals to obtain the necessary figures concerning antibiotic consumption. The amount of antibiotic consumption was expressed in Defined Daily Dose/1000 hospital day. The great differences found between hospitals in quality of antibiotic consumption related to the same subspeciality can be due to the different therapeutical approach in the respective departments. Quality of drug utilisation did not meet the expectations of the modern antibiotic therapy. Relatively low consumption was found in departments of ophthalmology, neurology, psychiatry and rehabilitation. Medium amount of antibiotic consumption was recorded in departments of internal medicine, general surgery, traumatology, obstetrics and gynecology, E. N. T. and dermatology. High antibiotic consumption was observed at the departments of urology, intensive care, infectology, pediatrics and pulmonology. Authors emphasise the importance of the education of the usage of antibiotics both at the medical universities and in postgraduate training as well. PMID- 7870416 TI - [Treatment of climacteric urogenital disorders with an estriol-containing ointment]. AB - Estriol containing cream for treatment of climacteric urogenital complaints was used. After 4 weeks local treatment with Ovestin cream atrophy of vaginal epithelium and chronic vaginitis stopped or significantly decreased. During the treatment the ratio of superficial and intermedier cells in the vaginal epithelium increased and the vagina showed a decrease of pH. The subjective complaints relating to the estrogen deficiency (vaginal burning and dryness, itching, dyspareunia and urinary dysfunctions) ceased. Side-effects and complications during the treatment were not found. The cream can easily be used and it is well tolerated. Estriol containing cream is suitable for the treatment of chronic vaginitis and cystitis developed on the base of climacteric epithelium atrophy of urogenital system. Its introduction to the local therapy is necessary because the majority of population of women are interested in it. PMID- 7870419 TI - Are mass cancer screenings effective? PMID- 7870418 TI - [Mobile multiple left chamber thrombi causing multiple embolism in the limbs requiring surgery]. AB - The authors report on the case of a 35-year-old man with multiple risk factors, who was sent to cardiac examination in order to find the cause of microembolisms on his fingers of his hands and on his right leg. According to the history and the ECG the patient had suffered an anterior myocardial infarction at home two months before the embolisms which had not been detected at that time. Performing 2D echocardiography, wall motion abnormality indicating anterior myocardial infarction and several thrombi were found as the source of embolisms. One of the thrombi were highly mobile. During 7 week of anticoagulant therapy there was no new embolism but the thrombi did not show regression, therefore the patient was sent to the Hungarian Institute of Cardiology where successful thrombectomy and revascularisation were performed after transoesophageal echocardiography and coronarography. At two year follow-up after the surgery there was no new thrombus detected. In connection with the case the authors surveyed the literature of left ventricular thrombus formation following myocardial infarction. PMID- 7870420 TI - Laser tissue effects with regard to otorhinolaryngology. AB - The multitude of medical laser systems with different wavelengths and technical appliances implicates the necessity of fundamental knowledge about the effects of laserbeams on living tissue. This is necessary to allow sufficient and therefore successful results for the patient. In this paper tissue effects of the mostly used lasers in otorhinolaryngology, CO2 laser and Nd:YAG laser will be presented. Influence on blood and lymphatic vessels, wound healing, and several CO2 laser parameters will be discussed. PMID- 7870421 TI - [Endoscopic treatment of iatrogenic tracheal stenosis by laser Nd:YAG]. AB - The authors present the technique and results of endoscopic Nd:YAG laser treatment of inflammatory tracheal stenoses. This kind of therapy was employed in 10 patients with tracheal stenosis, resulting from long-term nastotracheal intubation (6 cases), tracheostomy tube after radical laryngectomy (3 cases) and tracheal trauma. The laser fiber was introduced into trachea by the operative channel of a flexible bronchoscope and vaporization of obstructing tissues carried out using contact method in continuous mode of light emission (power 7-20 Watts). The achievement of normal tracheal patency usually required several laser therapy sessions (3-5), repeated in 3-5 days intervals. The short-term results are encouraging: in all cases the normal tracheal was lumen was restored, resulting in alleviation of patients' symptoms. In 3 cases a recurrent tracheal stenosis, requiring additional laser treatment was observed. PMID- 7870422 TI - [Diagnostic value of computer tomography of paranasal sinuses in qualifying for functional endoscopic sinus surgery (FESS)]. AB - Functional endoscopic sinus surgery (FESS) introduced in the recent years by Messerklinger, Stammberger and Kennedy gained undisputable reputation as method of choice in treatment of nose and nasal sinus diseases. The introduction of this method was possible, among others, due to precise radiological diagnostics (CT). Traditional radiological examinations of nasal sinus do not allow for detailed diagnostics and analysis of anatomic anomalies such as: dehiscention in vicinity of carotic artery or ophtalmic nerve which have basic significance while establishing surgical risk. The paper presents 20 cases of nasal sinus CT of patients qualified for functional endoscopic surgery comparative analysis with traditional radiograms were performed. PMID- 7870423 TI - [Multifocal status and malignant transformation of pleomorphic adenoma]. AB - A rare case of multifocal and malignant pleomorphic adenoma in 60-years--old male is presented. Its diagnosis was made on the basis of the case--history, clinical picture and biopsy. The clinical course and therapeutic tactics are briefly described. The conclusion of prognosis in this pleomorphic adenoma form is difficult. PMID- 7870424 TI - [The transseptal approach in transsphenoidal surgery of pituitary neoplasms]. AB - The authors described the direct transseptal approach in transsphenoidal surgery for hypophyseal tumors. This route gives a good insight into the area of the sella. The above mentioned method is also less destructive to nasal structures in the nasal cavity, because preserves the anterior nasal septum. It is uniformity of actually views of rhinological school. 20 patients were operated using this method and none of them noticed the changes of nasal airway and the sense of smell. PMID- 7870425 TI - [Primary adenoid carcinoma of the larynx and upper part of trachea]. AB - The aim of this study is presentation of two cases primary adenoid cystic carcinoma in subglottic part larynx and upper part trachea. Both were treated by surgical resection with following radiotherapy. Observation period in one case without any recurrent signs and neoplasmatic dissemination is 16 years. PMID- 7870426 TI - [Platysma myocutaneous flap in intraoral reconstruction]. AB - Plastyma myocutaneous island flap was used in 13 patients to reconstruct tissue defect after oral cancer surgery. Necrosis of the skin island in the oral cavity occurred in 3 patients. A fistula developed in one patient with a large defect of the tongue, pharynx and mandible. In 12 patients wound healing on the neck was good. Plastyma myocutaneous flap is very useful to close defects of the floor of the mouth and up to the half of the tongue width. PMID- 7870427 TI - [Laryngeal changes in mucoviscidosis]. AB - Mucoviscidosis (cystic fibrosis) is congenital and hereditary disease of excretion glands expose in infancy and school age. In clinical practice we very rare meet cases of mucoviscidosis with laryngological symptoms. Our study include 5 children examined in Children Hospital in Cracow. Three children were operated due to polyps in nose and paranasal sinuses. Two children are observed due to return infections in the parotid glands. PMID- 7870428 TI - [Administration of the cervical torsion test by the examination of Doppler's blood flows in vertebral arteries and basilar artery in patients with degenerative cervical spine changes]. AB - Using the neck rotation test during examination of Doppler's blood flows in vertebral arteries and basilar artery, the authors examined 60 subjects aged 16 60 years, including 20 healthy ones and 40 with cervical spondylarthrosis. The Transpect-TCD was used. Half the patients with cervical spine changes had also receptive hearing damage of low degree. The study demonstrated that neck rotation affected of patological Doppler's blood flows in one or in both vertebral arteries at 50% patients with cervical spondylarthrosis, but without clinical symptoms, and at 70% patients with cervical spondylarthrosis and clinical symptoms. The neck rotation test can have diagnostic significance by examination of sufficiency in vertebrobasilar system, or qualitative significance to microsurgical treatment. PMID- 7870429 TI - [Computer system of electronystagmographic examination. Part II. Analysis of nystagmus]. AB - It is a description of automatic registration and analysing of the eyes movement. In this method had beed applied a test of the eye movement in the limited momentary speed, test of the time taken by the deflection and the test of unanimity in analysing both deflection and direction of the quick phase. The analysis procedure has two stages. In the first stage the signal undergoes an introductory analysis which is aimed at smoothing it out and approximating it a saw-toothed shape. At this stage the computer identifies the phases, direction of nystagmus and deflection which are not real eye deflections. In the second stage the computer makes measurements of nystagmus parameters. PMID- 7870430 TI - [The application and usage of the bone-anchored hearing aids (BAHA)]. AB - This article describes the mode of operation of temporal bone-anchored hearing aids (BAHA) based on the phenomenon of osseointegration, and the otiatric and audiologic criteria used in the selection of patients for implantation of this device. The technical details of the two-step implantation of a titanium anchor for BAHA within the mastoid process are described. The difficulties associated with this procedure are analyzed based on our own experience with implants placed in 3 patients. PMID- 7870431 TI - [Preliminary results of otoacoustic emission measurement and standard values in young subjects with normal hearing. Part II. Measurement of effects of acoustic distortion]. AB - The paper discusses the results of DPOAE measurement in 44 young subjects with normal hearing capacity. The measurements were carried out separately for each ear (88 measurements altogether). Otoacoustic responses to continuous two-tone stimulation (f1 and f2) with an intensity range of 46-71 dB SPL were recorded. Mean DPOAE values from 2f1-f2 measurement for the right ear in males and females varied from 2.6 +/- 5.6 to1 5.4 +/- 6.9 (within the range 0.7-6.0 kHz). For the left ear the respective values were 3.9 +/- 4.7 to 19.1 +/- 4.0. In most of subjects an increase in DPOAE values for frequencies higher than 3 kHz was found, which is characteristic of middle ear emission. The statistical analysis of DPOAE measurements in males and females did not reveal significant differences except for a few parameters. In both sexes the intensity of f1 and f2 stimuli at the frequency of 1.5 kHz was found to be significantly different at p = 0.48. The results of DPOAE measurements can be regarded as a statistical probability of standard. In view of the lack of approved calibration standards, the data obtained from the study will be considered a local set of standard values and will be used for clinical interpretation of pathological cases. PMID- 7870432 TI - [A case of cervical air cyst]. AB - The rare case of cervical air cyst was described. The diagnostic difficulties, treatment and clinical course were discussed. PMID- 7870433 TI - [A different manner of using the nutritive drain in laryngectomized patients]. AB - Authors present own manner of putting of nutritive drain laryngectomy patients during operation. They described good points and faults of this method which they use in their practice after all laryngectomies. PMID- 7870434 TI - [Cervical lymph nodes metastases from the unknown primary neoplasm]. PMID- 7870435 TI - Effects of contralateral white noise stimulation on transitory evoked otoacoustic emissions in patients with acoustic neuroma. AB - Transitory evoked otoacoustic emissions are normal phenomena observed in most persons with hearing levels greater than 35 dB. Further, masking of the contralateral ear produces amplitude reductions in the transitory evoked otoacoustic emissions. We have undertaken a study of transitory evoked otoacoustic emissions in 20 patients with acoustic neuroma. All patients were assessed for transitory evoked otoacoustic emissions bilaterally, with and without contralateral masking with white band noise at 40, 50, and 60 dB. We found that transitory evoked otoacoustic emissions were present in 30% of ears with tumor and that the presence of transitory evoked otoacoustic emissions is associated with improved preoperative hearing levels, but that tumor size is not associated with the presence or absence of transitory evoked otoacoustic emissions. The amplitude of transitory evoked otoacoustic emissions from ears with tumor, when present, is decreased when compared with normal ears of normal patients. Further, with contralateral masking little of the amplitude reduction observed in normal patients is observed in the ears with acoustic neuroma. However, with masking of the contralateral ear, the ear without tumor demonstrated significantly greater amplitude reductions than normal ears from normal patients (p = 0.0006). Pertinent anatomy and possible explanations for these findings are discussed. PMID- 7870436 TI - Head and neck space infections in infants and children. AB - A retrospective study was performed in 117 children with head and neck space infections treated at the Children's Hospital of Pittsburgh from January 1986 through June 1992. Peritonsillar space infections were the most common (49%), followed by retropharyngeal (22%), submandibular (14%), buccal (11%), parapharyngeal (2%), and canine (2%) space infections. The most common pathogens isolated (N = 78) were the aerobes beta-hemolytic streptococcus (18%) and Staphylococcus aureus (18%), the anaerobes Bacteroides melaninogenicus (17%) and Veillonella (14%), and the gram-negative organism Haemophilus parainfluenzae (14%). beta-Lactamase production by aerobic pathogens was detected in 22% of cultures. Computed tomography scans (N = 16) were reviewed in blinded fashion and compared with operative findings. The sensitivity of computed tomography scan in detecting the presence of an abscess vs. cellulitis was high (91%), whereas the specificity was rather low (60%). Treatment of head and neck space infections in children should consist of accurate physical diagnosis aided by imaging studies, empiric antibiotic therapy that covers gram-negative and beta-lactamase- producing organisms as well as gram-positive organisms and anaerobes, and timely surgical intervention, when indicated. PMID- 7870437 TI - Database for vertigo. AB - An interactive database has been developed to assist the diagnostic procedure for vertigo and to store the data. The database offers a possibility to split and reunite the collected information when needed. It contains detailed information about a patient's history, symptoms, and findings in otoneurologic, audiologic, and imaging tests. The symptoms are classified into sets of questions on vertigo (including postural instability), hearing loss and tinnitus, and provoking factors. Confounding disorders are screened. The otoneurologic tests involve saccades, smooth pursuit, posturography, and a caloric test. In addition, findings from specific antibody tests, clinical neurotologic tests, magnetic resonance imaging, brain stem audiometry, and electrocochleography are included. The input information can be applied to workups for vertigo in an expert system called ONE. The database assists its user in that the input of information is easy. If not only can be used for diagnostic purposes but is also beneficial for research, and in combination with the expert system, it provides a tutorial guide for medical students. PMID- 7870439 TI - Nystagmus and postural instability after headshake in patients with vestibular dysfunction. AB - Nystagmus after rapid head-shaking (post-headshake nystagmus) is often seen in patients with vestibulopathy. Post-headshake nystagmus is transient and is frequently associated with symptoms of dizziness, dysequilibrium, or vertigo. The phenomenon presumably reflects headshake-induced asymmetry in vestibulo-ocular reflex pathways, which persists after head-shaking stops. We postulated that the same vestibular imbalance that underlies post-headshake nystagmus might produce an equivalent in postural instability. To test this hypothesis, we investigated the effect of headshake on postural control and eye movements in patients who exhibited post-headshake nystagmus, vestibulopathy, or both. Postural instability was quantified with a dynamic platform device, whereas eye movements were recorded with electrooculography. Ten normal controls and 21 patients with a history of post-headshake nystagmus or unilateral vestibulopathy were evaluated. Subjects were tested for 20 seconds before and immediately after passive horizontal headshake (+/- 30-degree amplitude) at 2 Hz for 20 seconds. Postural stability was assessed while subjects stood with eyes closed, and the floor was modulated proportionally with sway. The difference in normalized peak-to-peak sway (equilibrium score) before and after headshake was assessed in all subjects and compared between groups. Post-headshake nystagmus was documented by electro oculography recorded during posturography. Results for normal controls and vestibulopathic subjects without post-headshake nystagmus showed only a small transient decline in postural stability after headshake. Those with post headshake nystagmus (regardless of caloric asymmetry) showed a robust decline in postural stability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870438 TI - c-erbB-2/neu oncogene and Ki-67 analysis in the assessment of palatal salivary gland neoplasms. AB - To evaluate the role of the Ki-67 proliferation antigen and c-erbB-2/neu oncogene expression in the clinical assessment of salivary gland tumors, we followed up 71 patients with minor salivary tumors of the palate. All benign neoplasms (n = 18) showed low Ki-67 scores (< 12%), whereas 26% (14 of 53) of malignant neoplasms manifested high Ki-67 scores (> 12%). A significant statistical difference between Ki-67 scores for benign and malignant neoplasms was observed (p < 0.001). Ki-67 index also correlated significantly with malignant tumor grade (p = 0.04) and patient survival (p = 0.02). Only 1 of the 18 benign tumors had c-erbB-2/neu oncogene overexpression. A significant difference between c-erbB-2/neu overexpression in benign and malignant tumors was observed (p = 0.01). Overexpression of c-erbB-2/neu oncogene was noted in 38% (16 of 42) of malignant tumors and was significantly associated with aggressive tumor behavior (p < 0.001). Multivariate analysis of significant factors revealed that gender, tumor stage, and c-erbB-2/neu oncogene overexpression were jointly predictive of survival. Our data indicate that although the Ki-67 proliferating antigen and c erbB-2/neu oncogene expression may reflect certain intrinsic biologic properties of these neoplasms, only c-erbB-2/neu overexpression is significantly associated with their biologic aggression. PMID- 7870440 TI - Results of surgical salvage for radiation failures of laryngeal carcinoma. AB - The results of surgical salvage of radiation failures of laryngeal carcinoma were reviewed. There were 167 stage T3 and T4 patients. The operative mortality was 7%. The complication rates were 8% wound infection, 13% chest complication, and 25% anastomotic leakage. After the first salvage operation, pharyngeal recurrence developed in 28 (18%) patients. Seven (25%) patients were feasible for second salvage operation, and none of them had further local recurrence. There were 9 (5%) tracheostomal recurrences. Of the 126 N0 patients, 23 (18%) had nodal recurrence, and only 5 of the nodal recurrences were feasible for salvage by radical neck dissection. All 41 node-positive patients underwent radical neck dissection, and 9 (23%) had nodal recurrence. Of the 126 node-negative patients, 19 (15%) had distant metastasis. Of the 41 node-positive patients, 18 (44%) had distant metastasis. The node-positive patients had a significantly high distant failure rate despite locoregional control of tumor. The adjusted 5-year survival rate of T3-4N0M0 was 45%, and that of T3-4N + M0 was 22%. PMID- 7870441 TI - Management of the open labyrinth. AB - Labyrinthine fistulas occur in approximately 5% of cholesteatoma cases, but the management of this difficult problem remains controversial. This study assessed the preoperative presentation and outcome in 37 patients operated on for cholestatoma complicated by labyrinthine fistula. Therapy involved removing the matrix from each fistula and reconstructing the bony wall of the labyrinth with bone dust, fibrin glue, and perichondrium. Corticosteroids were added to the management protocol in more recent cases. A fistula classification scheme was introduced to standardize the reporting of the extent of labyrinthine involvement and results of treatment. The most common preoperative symptoms, sensorineural hearing loss and vertigo, were notably lacking in more than 30% of patients. The fistula test was positive in only 32% of cases. Corticosteroids were seen to have a beneficial impact on postoperative outcome in those cases involving injury to the membranous labyrinth or removal of perilymph. PMID- 7870442 TI - Identification of problem foods using food and symptom diaries. AB - Food and symptom diaries were used to identify problem foods for each of 164 patients with chronic medical problems such as headache, fatigue, congestion, abdominal pain, and sinus problems. A statistical analysis related the total load of 90 biologic families, as well as caffeine, alcohol, and lactose, to changes in symptom intensity during a 2-week diary. The results helped 75% of the patients when used as a guide for elimination diets. Open challenges confirmed 47% of the identified food components. This study required a database and software to estimate recipe components for an average of 243 foods per patient. The analysis of each patient's diary produces a main report that lists suspect food components for each symptom. The report lists components in decreasing order of statistical confidence and gives lag times between food ingestion and symptom change. This report also shows that initial direction of the symptom change as a direct or masking effect. Foods that appear "safe" or unrelated to the symptoms are also listed. A second report lists the patient's food sources for each of the suspected food components. The report shows the percentage contribution of source foods and is useful for patient education and the design of elimination diets. PMID- 7870443 TI - Congenital angiotensin-converting enzyme deficiency presenting as recurrent angioedema of upper airway in adult life. AB - In summary, a rare case of congenital ACE deficiency is presented. This disorder is of concern to the otolaryngologist because the patient in question had episodes of recurrent upper airway angioedema. Management of angioedema generally consists of self-administered epinephrine because these patients respond poorly to steroids. PMID- 7870445 TI - Perilesional interleukin-2 in the VX-2 carcinoma in rabbits: a preliminary investigation. AB - Immune system amplification by perilesional injection of interleukin-2 is a promising adjuvant approach for treating squamous cell carcinoma of the head and neck. A pilot study was designed to develop an animal model bearing squamous cell carcinoma in which to test the efficacy of perilesional interleukin-2. Rabbits were inoculated intramuscularly with the papilloma virus-induced squamous carcinoma VX-2 cell line. Tumor regression and host lymphatic response after perilesional interleukin-2 were measured. Variable responses were found. Growth of tumor cells implanted from cell culture was rapid in most animals. Tumor growth was prevented in animals receiving 10,000 units of interleukin-2 per injection initiated 9 days after tumor inoculation. This inhibition approached statistical significance when compared with growth of saline controls. Histologic responses consisted primarily of plasma cell and eosinophil infiltration. The intensity of the inflammatory response did not correlate with interleukin-2 dose. A trend toward enhanced tumor growth was seen with lower doses of interleukin-2 and when interleukin-2 therapy was initiated simultaneously with tumor inoculation. These findings suggest that high-dose recombinant interleukin-2 can prevent tumor growth if initiated after tumor inoculation. Whether this effect was caused by direct tumor cytotoxicity or mediated by the immune system is unclear. These preliminary results underscore the importance of understanding the effects of dose and schedule in the design of immunotherapy models before clinical use. PMID- 7870444 TI - Electronic integration of glottic closure and circopharyngeal relaxation for the control of aspiration: a canine study. AB - Aspiration can result from muscular weakness or paralysis of laryngopharyngeal muscles after lower motor neuron disorders (e.g., stroke) or unchecked gastroesophageal reflux. We submit that rehabilitation of the finely tuned swallowing mechanism should provide at least restoration of the normal dynamic relationships between glottic closure and cricopharyngeal relaxation. In three dogs under general endotracheal anesthesia, the recurrent laryngeal nerves and the pharyngeal musculature were exposed through a midline cervical incision. A tracheotomy was performed to allow unhindered laryngoscopic exposure of the vocal cords. A no. 9 endotracheal tube passed through the upper esophageal sphincter was used as a pressure transducer by saline inflation of its cuff and linked to an oscilloscope. The cricopharyngeus was placed under baseline tension with pulse trains administered by an intramuscular needle with a circuit previously used for agonist/antagonist coupling of reinnervated facial musculature. A second output channel was linked to the contralateral recurrent laryngeal nerve by a bipolar electrode. As the pulse width of the current to the recurrent laryngeal nerve increased, that to the cricopharyngeus was reciprocally decreased, producing snug glottic closure and synchronous cricopharyngeal relaxation. Results were documented on videotape. These findings were highly reproducible. We believe that the novel approach proposed in the current model offers an attractive solution to long-term aspiration problems resulting from an imbalance between vocal cord and cricopharyngeal activities. PMID- 7870446 TI - Diesel exhaust, diesel fumes, and laryngeal cancer. AB - A hospital-based, case-control study of 235 male patients with laryngeal cancer and 205 male control patients was conducted to determine the effects of exposure to diesel engine exhaust and diesel fumes and the risk of laryngeal cancer. All patients were interviewed directly in the hospital with a standardized questionnaire that gathered information on smoking habits, alcohol consumption, employment history, and occupational exposures. Occupations that involve substantial exposure to diesel engine exhaust include mainly truck drivers, as well as mine workers, firefighters, and railroad workers. The odds ratio for laryngeal cancer associated with these occupations was 0.96 (95% confidence interval, 0.5 to 1.8). The odds ratio for self-reported exposure to diesel exhaust was 1.47 (95% confidence interval, 0.5 to 4.1). An elevated risk was found for self-reported exposure to diesel fumes (odds ratio, 6.4; 95% confidence interval, 1.8 to 22.6). No association was observed between jobs that entail exposure to diesel fumes, such as automobile mechanics, and the risk of laryngeal cancer. These results show that diesel engine exhaust is unrelated to laryngeal cancer risk. The different findings for self-reported diesel fumes and occupations that involve exposure to diesel fumes could reflect a recall bias. PMID- 7870447 TI - Smoking and middle ear disease: are they related? A review article. AB - The relationship between passive smoking and middle ear disease was reviewed. The hypothesis that acute otitis media, serous otitis media, and related diseases in children are caused by inhalation of second-hand smoke has been accepted by many. We reviewed the literature on this topic. There are many studies that do not support the hypothesis. There is no indication that the smokers themselves have a higher incidence of middle ear disease. Considering the difficulty of publishing negative studies, the need for academics to publish significant findings, and the poor foundation for some authors' conclusions in the literature, we find that the literature does not offer sufficient support for the hypothesis that second-hand smoke causes middle ear disease to accept the hypothesis. PMID- 7870448 TI - One-stage repair of congenital laryngeal webs. PMID- 7870449 TI - Central mucoepidermoid carcinoma of the mandible. PMID- 7870450 TI - Implications of bone pate in cochlear implant surgery. PMID- 7870451 TI - A noncaseating granulomatous lesion of the tonsil presenting as a malignant neoplasm. PMID- 7870452 TI - Perithyroid Teflon granuloma mimicking a thyroid nodule. PMID- 7870453 TI - Traumatic cerebrospinal fluid fistula presenting as recurrent meningitis. PMID- 7870454 TI - Management of internal jugular vein phlebectasia. PMID- 7870455 TI - Lingual dermoid cyst. PMID- 7870456 TI - Tortuous internal carotid artery presenting as an oropharyngeal mass. PMID- 7870457 TI - Development of a schwannoma within a facial nerve neurofibroma: a case report and literature review. AB - We report the presence of a schwannoma within a neurofibroma of the intratemporal facial nerve. This neurofibroma recurred 39 years after its first excision in the parotid gland. Although some believe that schwannomas and neurofibromas represent the same entity, these tumors present distinctive histopathologic and clinical characteristics, which are discussed. The extreme rarity of a schwannoma developing within a neurofibroma is underlined. This is the first report of such an association occurring within a cranial nerve. PMID- 7870458 TI - Otosyphilis in a patient with human immunodeficiency virus: internal auditory canal gumma. PMID- 7870459 TI - Human immunodeficiency virus--associated non-Hodgkin's lymphoma presenting as an auricular perichondritis. AB - AIDS-related NHL is an aggressive neoplasm, usually of high or intermediate grade, frequently extranodal at initial treatment, and often the first manifestation of AIDS. Although complete remissions have been reported, they occur in only a minority of patients. We describe a patient with NHL of the external ear that masqueraded as an auricular perichondritis. This is the first case reported in which AIDS-related NHL first appeared in the ear, and this should alert physicians who treat patient with AIDS to be aware of the protean manifestations of this disease. PMID- 7870460 TI - Malignant teratocarcinosarcoma of the sphenoid sinus. AB - We have presented the first reported case of malignant teratocarcinosarcoma arising in the sphenoid sinus treated successfully with surgery and radiation therapy. The patient shows no signs of recurrence 5 years after surgery. The combined head and neck/neurosurgical approach using complete rhinotomy and medial maxillectomy with transsphenoid/transethmoid approach is advocated for sphenoid sinus tumors of this type. PMID- 7870461 TI - Adenoid cystic carcinoma of the nasopharynx. PMID- 7870462 TI - The profile of IgG1 and IgG2a antibody responses in mice exposed to Schistosoma mansoni. AB - The segregation of IgG2a and IgG1 immunoglobulin isotypes as markers for Th1 and Th2 lymphocytes respectively, was investigated in mice exposed to normal or optimally-irradiated S. mansoni cercariae. Using a panel of ELISAs, soluble antigens from lung-stage schistosomula, adult worms, or eggs, were probed with serum samples collected at biweekly intervals. Infected mice developed increased IgG1 responsiveness to all three antigens, especially between weeks five and seven, whereas IgG2a responses were lower, particularly to egg antigens. This confirms that Th2 responses are dominant after the onset of patency in infected mice. In comparison, vaccinated mice developed lower levels of IgG1, and higher levels of IgG2a to larval and worm antigens. Thus, they had balanced expression of IgG1 and IgG2a, despite having a dominant Th1 lymphocyte population. An elevated IgG1 response to egg antigens in vaccinated mice challenged with normal parasites, occurred two weeks later than in normal mice. Mice exposed to male only cercariae developed IgG1 and IgG2a antibodies to larval and worm antigens. However, they also had elevated IgG1 to egg antigens from week five, despite a total absence of eggs. Therefore, adult worm antigens may cross react with the egg and stimulate the switch to Th2 dominated responsiveness. PMID- 7870463 TI - Praziquantel-induced exposure of Schistosoma mansoni alkaline phosphatase: drug antibody synergy which acts preferentially against female worms. AB - The efficacy of praziquantel-treatment of murine Schistosoma mansoni-infections can be enhanced by concurrent administration of rabbit anti-sera with specificity for parasite antigens. Monospecific rabbit serum raised against S. mansoni worm alkaline phosphatase, that was reactive with the enzyme on the drug-treated female surface, was found to significantly and preferentially increase the mortality of female worms by PZQ. Immunoglobulins purified from the anti-alkaline phosphatase antiserum inhibited 54% of schistosome alkaline phosphatase enzymatic activity on the surface of praziquantel-treated worms. We propose that synergistic antibody-mediated death of drug-damaged worms is a consequence of the inhibition of drug-exposed alkaline phosphatase on the female worm surface by passively transferred antibody. PMID- 7870464 TI - Strongyloides venezuelensis infection in Syrian golden hamster, Mesocricetus auratus, with reference to the phenotype of intestinal mucosal mast cells. AB - Syrian golden hamster, Mesocricetus auratus, was found to be a moderately susceptible host for the intestinal helminth, Strongyloides venezuelensis. After infection by subcutaneous inoculation with 3000 infective larvae (L3), about 20% of them became adult worms in the small intestine, and, after a stable infection up to day 20, adult worms were slowly and gradually expelled towards day 45. Before infection, mast cells in the jejunum were about 30/10 villus crypt units and over 80% of them were formalin-resistant and berberine sulphate-fluorescence positive. After infection with S. venezuelensis, the number of intestinal mast cells gradually increased with time and about a half of them were formalin sensitive and berberine sulphate fluorescence-negative. Intraepithelial migration of mast cells was never seen before and after infection. Heterogeneity of mucosal mast cells in terms of granular proteoglycans was further confirmed by the determination of critical electrolyte concentration. In spite of the heterogeneity of proteoglycans, enzyme-histochemical study revealed that practically all mucosal mast cells of Syrian golden hamsters were positive for chymase but negative for tryptase. Mast cells in the skin and tongue were also positive for chymase but negative for tryptase. Together with our previous study on mucosal mast cells of other rodents, phenotypic variances of mucosal mast cells seem to be closely related to the protective capacity against the genus Strongyloides. PMID- 7870465 TI - Goblet cell mucins of four genera of the subfamily Cricetinae with reference to the protective activity against Strongyloides venezuelensis. AB - Goblet and mast cell responses in the jejunum of four genera, Mesocricetus auratus (Syrian hamster), Phodopus campbelli, Cricetulus griseus (Chinese hamster), and Tscherskia triton, belonging to the subfamily Cricetinae, were examined after infection with Strongyloides venezuelensis. Parasite eggs became detectable in faeces of all four genera on Day 7. Faecal egg count peaked around Day 8 in C. griseus and T. triton and around Day 14 in M. auratus and P. campbelli. In M. auratus and P. campbelli, faecal egg production persisted over 40 days, whereas that in C. griseus and T. triton rapidly terminated within 14 days. In all four genera examined, goblet cell hyperplasia and mastocytosis were observed at the time of expulsion of S. venezuelensis. However, in the comparative study of all four genera, neither the degree of goblet or mast cell hyperplasia nor the phenotype of mast cells correlated to the rapidity of the expulsion of S. venezuelensis. On the other hand, the rapidity of expulsion closely correlated with the degree of sulphation of goblet cell mucins because two genera, C. griseus and T. triton, having highly sulphated goblet cell mucins showed faster expulsion of S. venezuelensis than the other two genera, P. campbelli and M. auratus, having less sulphated mucins. These results suggest that physicochemical nature of mucins is critical for the expulsion of S. venezuelensis from the subfamily Cricetinae. PMID- 7870466 TI - Humoral immune responses to Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans in adult periodontitis and rapidly progressive periodontitis. AB - The relationships between various forms of periodontal disease and the avidities of serum antibodies of all 3 immunoglobulin (Ig) classes (IgG, IgM and IgA) to Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans were investigated. Twenty-four patients with untreated adult periodontitis and twelve untreated patients diagnosed as suffering from the early-onset form of periodontitis, rapidly progressive periodontitis, were studied. The latter group were matched for age and sex to healthy controls. Antibody titres were measured and avidity (expressed as molarity) was further assayed using the thiocyanate elution method. Avidity has previously been shown to relate to the biological function of antibody. IgM avidities to P. gingivalis were lower in the rapidly progressive periodontitis group than in the adult periodontitis group (0.54 M vs 0.74 M). IgG avidities tended to be lower in the former than in the latter group (0.58 M vs 0.92 M). In accordance with other workers, seropositivity was defined as an immunoglobulin titre more than twice the median level of control sera. Only 2 of the rapidly progressive periodontitis group were seropositive. Interestingly, the seronegative rapidly progressive periodontitis patients were significantly different (0.53 M vs 0.92 M). The data that patients with various forms of periodontal disease appear to produce antibodies of differing avidity to P. gingivalis suggest that the quality of the humoral immune response to suspected periodontopathogens may have a bearing on the aetiology of periodontal disease. PMID- 7870467 TI - The gingival immune response to periodontal pathogens in juvenile periodontitis. AB - A gingival explant culture system was utilized to evaluate the reactivity of local immunoglobulins produced by juvenile periodontitis tissue. Gingival explant culture supernatant fluids were screened, via a standardized dot-immunobinding assay, for antibodies reactive to: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Campylobacter rectus, Eikenella corrodens, Peptostreptococcus micros, Peptostreptococcus anaerobius, Capnocytophaga ochracea, Eubacterium nodatum and Fusobacterium nucleatum and one nonoral microorganism, Porphyromonas asaccharolytica. Of the 75 juvenile periodontitis supernatant fluids tested, the organisms that reacted with the highest numbers of supernatant fluids were E. nodatum (72%) and A. actinomycetemcomitans (49%). More juvenile periodontitis than healthy tissue samples showed supernatant fluid reactivity to P. intermedia, C. ochracea, E. nodatum and P. micros. No significant difference was observed between the juvenile periodontitis group supernatant fluids reactivity and the supernatant fluids of the other periodontal disease groups tested. Cluster analysis revealed the association, as determined by supernatant fluid reactivity, of P. micros and C. ochracea in the juvenile periodontitis group. The data from this investigation are consistent with a hypothesis of multiple possible etiologies of periodontal destruction in juvenile periodontitis and other forms of periodontal diseases. PMID- 7870468 TI - Gingival crevicular fluid antibody to Actinobacillus actinomycetemcomitans in periodontal disease. AB - We identified antibody isotypes and subclass proportions in gingival crevicular fluid to understand the potential protective ability of these antibodies towards infection with Actinobacillus actinomycetemcomitans. Immunoglobulin G (IgG) 1-4 antibody levels to A. actinomycetemcomitans serotype b were quantified in serum and gingival crevicular fluid from 20 periodontitis patients who had at least one subgingival plaque sample with cultivable A. actinomycetemcomitans. The subclass antibody levels in the patients' sera were IgG1 = IgG2 > IgG3 > IgG4. A portion of the gingival crevicular fluid samples had IgG (15.7%; range: 0-52%) and IgA (2.5%; range: 0-15%) antibody that was significantly elevated compared with serum. Gingival crevicular fluid samples with elevated IgG antibody were analyzed for the subclass distribution and showed elevated IgG3 (58%), IgG4 (35%), IgG1 (25%) and IgG2 (25%) antibody in the gingival crevicular fluid. These results demonstrated a characteristic distribution of both serum and gingival crevicular fluid IgG subclass responses to A. actinomycetemcomitans. We also examined the sites with elevated antibody in each subclass for the presence of A. actinomycetemcomitans in the subgingival microbiota. The results showed that > 95% of sites with elevated IgG4 were colonized, whereas < 50% of sites with elevated IgG2 demonstrated this microorganism. IgG2 and IgG4 levels were primarily elevated in diseased sites, whereas IgG4 elevations were absent in healthy sites. The frequency and distribution of antibody in the gingival crevicular fluid as related to colonization with this microorganism were consistent with localized host-parasite interactions at individual tooth sites. The relative subclass distribution of elevated gingival crevicular fluid antibody was shown to be IgG3 > IgG4 > IgG2 = IgG1. These antibody types suggest that the potential exists for this local antibody to A. actinomycetemcomitans to play an important role in the gingival sulcus in relationship to colonization and clinical presentation. PMID- 7870469 TI - Degradation of immunoglobulin G by periodontal bacteria. AB - Several subgingival microorganisms were tested for their ability to utilize human immunoglobulin G (IgG) as a substrate for growth. This was done using a protein free chemically defined medium, supplemented with IgG. Stimulation of growth was observed for Capnocytophaga ochracea, Porphyromonas asaccharolytica, Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella intermedia, Prevotella oralis, Lactobacillus catenaforme and Streptococcus intermedius. Immunoelectrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a protein assay demonstrated that P. intermedia and P. endodontalis completely degraded the protein chains of IgG. Partial breakdown of IgG was observed for P. asaccharolytica and C. ochracea, whereas P. oralis cleaved the IgG heavy chain, yielding Fc and Fab fragments. All these bacteria utilized IgG as a substrate for growth. Binding studies using an enzyme-linked immunosorbent assay, revealed complete loss of in vitro antigen-antibody binding capacity after incubation of specific IgG with P. endodontalis and partial loss of binding with P. intermedia, P. gingivalis, C. ochracea or Fusobacterium nucleatum. Degradation or inactivation of IgG by oral bacteria is thought to be important in the causation of polymicrobial infections. PMID- 7870471 TI - Effect of binding of fibrinogen to each bacterium on coaggregation between Porphyromonas gingivalis and Streptococcus oralis. AB - Fibrinogen inhibits the coaggregation between Porphyromonas gingivalis and Streptococcus oralis. In this study, we determined which bacterium interacts with fibrinogen in this inhibitory process. Although preincubation of each bacterium with fibrinogen did not inhibit coaggregation, its activity was completely eliminated by the addition of protease inhibitors such as N-ethylmaleimide (NEM), p-chloromercuriphenyl sulfonate and N alpha-p-tosyl-L-lysine chloromethyl ketone to the preincubation mixture with fibrinogen and P. gingivalis. However, the inhibition of coaggregation was not found after preincubation of S. oralis with fibrinogen in the presence or absence of the protease inhibitors. Labelled materials were recovered from the extract of P. gingivalis cells incubated with radioiodinated fibrinogen in the presence of NEM but not in the absence of NEM. In the binding experiment, P. gingivalis showed a much higher binding activity to fibrinogen than S. oralis. These findings suggest that fibrinogen and its fragment(s) may mask directly or indirectly the aggregation site with S. oralis on the P. gingivalis cells in its inhibitory process of coaggregation. PMID- 7870470 TI - Carbohydrate depletion of immunoglobulin A1 by oral species of gram-positive rods. AB - Bacterial deglycosylation of immunoglobulin Al (IgA1), the dominant isotype of antibody in the oral cavity, probably provides both nutrition as well as protection to the oral bacterial community. Representative strains of oral gram positive rods were tested for their ability to remove carbohydrates from IgA1. Detection of sialic acids was performed by means of high-performance liquid chromatography (HPLC) separation (Aminex HPX-87H) and ultraviolet light absorption at 190 nm, and neutral carbohydrates were measured by HPLC separation (Capcell Pak C-18 SG 120) and ultraviolet light absorption at 245 nm after derivatization. Four strains of Actinomyces naeslundii, two strains of Corynebacterium matruchotii and one of two strains of Actinomyces odontolyticus partially or totally removed sialic acid, while two strains of Propionibacterium propionicus and the other strain of A. odontolyticus did not. Complete correlation was observed between sialic acid removal, neuraminidase activity measured with fluorogenic substrate and with one exception, altered immunoelectrophoretic mobility of IgA1. Only limited removal of other carbohydrates was observed with poor correlation to exoglycosidase activities measured with chromogenic substrates. Desialylation increases the susceptibility of glycoproteins, including IgA1, to proteolysis. Therefore, the desialylation of IgA1 by oral gram-positive rods may facilitate the proteolytic activities of other oral bacteria, and the concerted action may positively influence the survival of the bacteria in the oral community. PMID- 7870472 TI - Kinetics of lactose-reversible coadhesion of Actinomyces naeslundii WVU 398A and Streptococcus oralis 34 on the surface of hexadecane droplets. AB - Most investigations of mechanisms accounting for intergeneric coaggregation have emphasized stereospecific rather than nonspecific interactions. The purpose of this investigation was to determine the relative importance of lectin carbohydrate and nonspecific hydrophobic and ionic interactions, using a model based on strains with one of the most well understood specific coaggregation mechanisms, the lactose-reversible coaggregation of Actinomyces naeslundii and Streptococcus oralis. The kinetics of coadhesion and desorption of coadherent bacteria were studied using S. oralis 34 bound to hexadecane droplets as an affinity support for the adhesion of A. naeslundii WVU 398A. Light, confocal microscopy and transmission electron microscopy confirmed that A. naeslundii cells adhered only to the S. oralis cells, not to exposed hexadecane between the streptococci. Coadhesion was inhibited by lactose concentrations as low as 2.0 mM. The rate of coadhesion was halved at 60 mM lactose. The hydrophobicity inhibitors bovine serum albumin and defatted bovine serum albumin and the salts LiCl and KCl failed to inhibit coadhesion in the hexadecane assay, and bovine serum albumin also failed to inhibit coaggregation in a bacterial aggregation assay on glass slides. High concentrations of the salts achieved a 50% rate decrease in A. naeslundii adhesion to the S. oralis-coated droplets only when they were combined with > 20 mM lactose. Sodium dodecyl sulfate (SDS) and Tween 20 inhibition was tested by the slide coaggregation assay because they tended to emulsify the droplets; SDS was inhibitory. Lactose selectively desorbed A. naeslundii from S. oralis-coated droplets at low concentrations equivalent to those that inhibited coadhesion. Neither LiCl nor KCl desorbed A. naeslundii from the droplets, even at 500 mM. At low concentrations, SDS but not Tween 20 eluted both A. naeslundii and S. oralis from the droplets. Although the SDS results might suggest a degree of cooperative charge interactions, the results support the hypothesis that stereospecific, beta-galactoside-sensitive interactions have a much greater impact than nonspecific interactions on the coadhesion of A. naeslundii and S. oralis. PMID- 7870473 TI - Initial catabolism of sorbitol in Actinomyces naeslundii and Actinomyces viscosus. AB - The initial steps of sorbitol catabolism were studied in 4 strains of Actinomyces naeslundii and Actinomyces viscosus that had been isolated from human dental plaque. Cell-free extracts were prepared from cells grown in the presence of either sorbitol, xylitol or glucose. The extracts from all strains grown on sorbitol had nicotinamide adenine dinucleotide-linked dehydrogenase activities for sorbitol and xylitol and reduced nicotinamide adenine dinucleotide-linked reductase activities for fructose and xylulose. Two of the strains also exhibited these activities when grown in the presence of xylitol, and all glucose-grown cells lacked them. The results indicate that sorbitol metabolism in oral actinomyces involve oxidation of sorbitol to fructose by an inducible enzyme, nicotinamide adenine dinucleotide-linked sorbitol dehydrogenase. This step is followed by the phosphorylation of fructose with guanosine triphosphate as a main phosphoryl donor. Thus, the initial catabolic pathway of sorbitol in A. naeslundii and A. viscosus is different from those described for other oral bacteria. PMID- 7870474 TI - Leukocyte adhesion molecules in oral lichen planus: a T cell-mediated immunopathologic process. AB - Oral lichen planus exhibits features of a mucosal type IV immunopathologic process. Adhesion molecules involved in the trafficking and homing of T lymphocytes to the subepithelial compartment were assessed by immunohistochemical methods. Laminin, type IV collagen and type VII collagen extracellular matrix components at the epithelial-connective tissue junction are significantly increased and serve as ligands for beta 1 integrins on lymphocyte membranes. Endothelial-associated intercellular adhesion molecule 1 and extracellular matrix basement membrane components are also significantly increased in the submucosa. Keratinocyte expression of major histocompatibility complex class II molecules and intercellular adhesion molecule 1 may serve as ligands for lymphocyte T cell receptor complex and beta 2 integrins, respectively. These adhesion molecules are probably involved in the trafficking of lymphocytes to the epithelial connective tissue interface in response to as of yet undefined antigens. PMID- 7870475 TI - Pharmacologic management of acute pain in the orthopaedic patient. AB - Postoperative pain remains undertreated. Barriers to adequate postoperative analgesia include lack of knowledge regarding pain and its management, inadequate assessment, preconceived notions by nurses and physicians regarding pain and addiction, and the continued use of PRN administration of medications instead of active intervention on a scheduled basis. Knowledge regarding the physiology of pain provides nurses with information necessary to control pain. Pharmacologic management includes the use of nonopioids, opioids, and various adjuvant drugs. Principles regarding the use of these analgesics guide the nurse to use these drugs to their greatest effect. The special needs of the very young and the elderly must also be considered. PMID- 7870476 TI - Back pain in children. AB - Back pain in children may be due to many causes, both orthopaedic and nonorthopaedic. As with adults, underlying pathophysiology is frequently multifactoral and includes both physiologic and psychologic components. Assessment should include a thorough age-appropriate history and physical examination, based on presenting symptoms. The nurse should be aware of the child's perception of pain and its meaning, as well as that of the family. Management of back pain in children should include not only referral to appropriate specialists as indicated, but also should include involvement of the family unit in the treatment plan. PMID- 7870477 TI - Discovery and recovery of an addicted nurse. AB - This author anonymously recounts her experience of discovering that her assistant head nurse was addicted. After being confronted and counseled, the nurse began treatment, and after 6 months, she was able to resume work at the hospital. The article points out what to be aware of regarding drug addiction in coworkers and what to do if you suspect someone. PMID- 7870478 TI - Addiction treatment for the nurse. AB - Health care workers, including nurses, have a higher risk of addiction than other professionals. The addicted nurse is often difficult to identify and has special needs in treatment and recovery. The goal of the treatment provider is to help the nurse return to productivity in the nursing profession, and at the same time, help the nurse preserve dignity. The nurse's right, recovery and return-to-work process, and legal considerations are all important aspects of addiction treatment. PMID- 7870479 TI - Myasthenia gravis: an overview. AB - Myasthenia gravis is a chronic autoimmune disease that results in progressive weakness of the striated muscles. Autoantibodies destroy acetylcholine receptor sites, preventing adequate nerve impulse conduction to the muscles. Medical treatment is directed at increasing the amount of available acetylcholine or at reducing the levels of circulating antibodies. Nursing care is complex and involves patient education about drug therapy and treatment options as well as caring for the numerous problems that arise from varying degrees of muscle weakness. Skilled nursing assessment and intervention can help protect the myasthenic patient from the life-threatening complications of respiratory compromise. PMID- 7870480 TI - Care of the injured pregnant patient. AB - Nursing care of the obstetric patient requires an understanding of normal changes that occur during pregnancy in order to make critical decisions concerning care for her and her infant. Trauma during pregnancy threatens not only the pregnant woman but also her infant. This article reviews the normal physiologic changes relating to pregnancy. It includes a checklist for orthopaedic nurses to use when caring for a pregnant patient. PMID- 7870481 TI - From the president: the gift. PMID- 7870482 TI - Technology's seductive power. AB - Advances in technology suggest new possibilities in health care and have become equated with state-of-the-art health care. The promise of technology has the potential to act as a seductive force luring nurses and other health care providers to use it and luring patients to request it. If nurses become so enchanted with technology, the patient as a person may be overlooked. By focusing on caring and the patient's experience of being ill, nurses can avoid being seduced by and dependent upon the use of technology when providing patient care. PMID- 7870483 TI - Health care reform and the 103rd Congress: past is prologue. PMID- 7870484 TI - Nurses helping nurses. PMID- 7870485 TI - Walking through gait analysis. AB - As medical technology advances, the assessment of complex tasks such as walking is becoming easier. Today's clinical gait analysis laboratory provides the essential tools for the quantification of pathologic gait patterns. Dynamic joint motion, muscle activity, and the forces acting on the body are documented via complex computer and camera systems. The information gained from the gait analysis is essential to the understanding of each individual's unique gait pattern. Gait analysis provides both the patient and the physician with valuable information that can be used to plan better treatment regimens. PMID- 7870486 TI - Predicting speech recognition thresholds from pure tone hearing thresholds. AB - Hearing sensitivity is most commonly still reported in terms of pure tone thresholds. Unfortunately, simple procedures for predicting Speech Recognition Thresholds from Pure Tone Thresholds are not currently available. To remedy this problem, pure tone thresholds were collected from 802 individuals over the range of 250 to 8000 Hz. Five subsets of pure tone thresholds which are commonly used to report hearing status were then considered. An average correlation of 0.878 was found between the various pure tone indexes and the speech recognition threshold. Using regressions between pure tone and the speech measure, a table was constructed that allows conversion of the various pure tone indexes to a predicted speech recognition threshold and involves only a very simple computation. PMID- 7870487 TI - Self-recognition in dementia of the Alzheimer type. AB - A prospective study of patients with moderate (n = 20) and severe (n = 19) dementia of the Alzheimer type was performed to compare the ability of patients to recognize themselves. A Mini-Mental State Examination cut-off score was used to separate those patients with severe dementia (MMSE score < 6) from those with moderate dementia (MMSE = 7--15). Each patient was then scored according to his ability to name two body parts correctly and to recognize himself in a mirror. Severe degrees of dementia were significantly associated with the inability of patients to recognize themselves while those with moderate degrees of dementia still retained this capacity. PMID- 7870488 TI - Comparing matching ability, spatial memory, and ideational fluency in boys and girls. AB - The purpose of our study was to examine whether girls and boys show patterns of problem-solving ability similar to those attributed by Kimura in 1992 to women and men, respectively. Subjects were 28 girls and 24 boys, aged 5-11 years, who were tested individually on matching ability, spatial memory, and ideational fluency, tasks on which women reportedly outperform men. No significant gender differences in these problem-solving abilities were found. On ideational fluency, the youngest girls were seven times more likely than young boys to give whimsical responses, but older girls were then times less likely than older boys to give whimsical responses. These results suggest that the patterns of visuospatial problem-solving abilities that Kimura ascribed to women and men are not present in preadolescent girls and boys. PMID- 7870489 TI - Causes of occupational injuries. AB - The causes of occupational injuries (N = 2,365) were investigated. Accidents with machinery and hand tools were the two main causes (49.9%). 89% of the patients with occupational injuries were male. The highest risk group were in the age category of 19 years or less (51.9%). This age group also showed the highest incidence rate for females. PMID- 7870490 TI - Mellow and frenetic antecedent music during athletic performance of children, adults, and seniors. AB - Previous research has yielded a contradictory picture of the effects of music on athletic performance. While athletes frequently report using music while training or during or before an event, laboratory studies have generally not detected a beneficial effect of music. The influence of music, judged mellow and frenetic, played before exercise was assessed by measuring stationary bicycle mileage. 60 volunteers from three age groups (child, adult, and senior) and with two levels of prior activity (high and low) were subjects. Each participant received three randomized 2-min. exercise trials, each preceded by 1-min. exposure to mellow music, frenetic music, or white noise. Mileage in both music conditions was significantly higher than that during the white-noise control trial except among the senior subjects. No significant differences between frenetic and mellow music were noted. PMID- 7870491 TI - Visual evoked potentials of adaptation to left-right reversed vision. AB - During the course of the adaptation to left-right reversed vision, visually, evoked potentials (VEPs) were measured for a light flash presented on either side of a fixation. The VEP amplitudes and latencies changed drastically as the adaptation progressed. The time course of the change was quite different between occipital scalp loci. These results indicate that the adaptation to the optical distortion takes place even in the relatively early stage of the visual information processing. PMID- 7870492 TI - Decrement and the illusions of the Mueller-Lyer figure. AB - Decrement, a time-related decrease in the magnitude of the Mueller-Lyer illusion, was measured separately for the wings-out and the wings-in variants of the Mueller-Lyer figure. There were significant reductions of wings-out illusion magnitude during the decrement period. Observers viewing the wings-in segment showed a non-significant decrement pattern. Analyses of individual decrement patterns showed that illusion magnitude did not decrease for a number of observers even when there were significant time-related trends at the group level. Data for 80 observers imply that the mechanisms of perceptual learning proposed by previous models of Mueller-Lyer illusion decrement are not sufficient explanations of the decrement process. PMID- 7870493 TI - Choice of violent vs nonviolent methods for suicide by immigrants. PMID- 7870494 TI - Experience of loss and subsequent suicide. PMID- 7870495 TI - Scholastic aptitude and rates of personal violence in the USA. PMID- 7870496 TI - Relations between creativity and intelligence among Malaysian pupils. AB - This paper describes an empirical study of the relation between creativity and intelligence of 397 Malaysian secondary school pupils. The Torrance Tests of Creative Thinking, Figural Form A and Verbal Form A (Malay Language version), and the Cattell Culture Fair Intelligence Test were administered to 181 boys and 216 girls from five secondary schools located in the urban and suburban areas of Kuala Lumpur and Petaling Jaya in Malaysia. Analysis indicated that scores on verbal creativity were related to intelligence while those on figural creativity were not. PMID- 7870498 TI - Effects of multiple sclerosis on physical and psychosocial functioning. AB - Significant impairment was measured across the board in the physical, psychosocial, and daily living functions of 24 multiple sclerosis patients. These findings support the need of MS patients for a comprehensive, multidisciplinary treatment approach to all areas affected by MS. PMID- 7870497 TI - Parental and peer influences on food consumption of preschool African-American children. AB - Sources of social influence on urban African-American preschool children's food consumption were coded from videotapes of noontime and evening meals of 42 children. The frequency of eating prompts was associated with the age of the child, the source (mothers, fathers, age mates, other adults, and day-care staff), and socioeconomic status. The success of the prompt in changing the child's eating behavior was dependent on the type of prompt. PMID- 7870499 TI - On the role of emotional traits in impression formation. AB - 280 Italian undergraduates (90 men and 190 women), ages 18 to 30 years, rated a warm, cold, jealous, or envious stimulus person on 15 7-point semantic differential scales. Varying the sex of the stimulus person, 8 different versions of the description were obtained. Factor analysis, carried out to identify a smaller set of non-redundant dimensions, yielded three factors. A multivariate analysis of variance, 4 (warm, cold, jealous, envious) x 2 (male stimulus person, female stimulus person) x 2 (male respondents, female respondents), indicated significant effects for the variable "trait" on the first and second factors, an interaction between the sex of the stimulus person and the sex of the respondent on the first factor, and an effect for the sex of the respondent on the second factor. The traits "envious" and "jealous" acted as central qualities, and the sex of the stimulus person and of the respondent played an important role in impression formation. Further implications of the finding were discussed. PMID- 7870500 TI - Reaction force and EMG analyses of wheelchair transfers. AB - To examine how reaction forces and muscle activity change when transferring from a wheelchair to three different heights, six male able-bodied college students were tested. Analysis indicated that transferring to a lower seat position generated a greater vertical reaction force and required more muscle effort from triceps and posterior deltoid muscles. Transferring to a higher seat position resulted in a shift of the friction force from the anterior-posterior to the medial-lateral direction, and more biceps muscle effort was needed to perform the up-rightward movement. Transferring to a seat at the same height required less muscle effort from the upper extremities. PMID- 7870501 TI - Participation in a wellness course and attitude toward physical education. AB - 70 women and 46 men enrolled in a college physical education course emphasizing concepts of wellness were administered the Attitude Toward Physical Activity Inventory at the beginning and end of a semester. Gender differences at the end of the semester were obtained on Social Experience, Health and Fitness, Aesthetic Experience, and Ascetic Experience, with the scores for men significantly higher than those for women. When comparing scores of students required to participate in the course with those of students electing to, no significant differences were found. Scores by gender showed significant differences on Ascetic Experience by men, with scores of noneducation majors significantly higher than those of education majors. Significantly higher scores at Time 2 for women on Health and Fitness and for men on Ascetic Experience were obtained. PMID- 7870502 TI - Bulimic symptoms and body-image characteristics among university women. AB - A nonclinical sample of 102 women students were given the BULIT-R to measure bulimic symptomatology and the Multidimensional Body-Self Relations Questionnaire, a multidimensional measure of body-image parameters. Statistically significant relationships between Appearance Evaluation, Appearance Orientation, and Illness Orientation subscales of the two inventories were identified. These findings indicate that women university students reporting higher scores on bulimic symptoms are more likely to report a general unhappiness with their physical appearance. PMID- 7870503 TI - Difference between long-term contact-lens wearers and nonwearers in amplitude of the return-sweep velocity of eye movements during reading. AB - A Beckman Type RM Dynograph was used to record eye movements of 31 college students, 23 of whom had never worn contact lenses and 8 who had worn contact lenses for at least five years and 12 hours a day, while reading equivalent print at a distance of 33 cm. Analysis showed that the deviation indexes of .28 and .26 were comparable, meaning that these two groups showed similar return-sweep velocity amplitudes. A difference of 1.73 mm/.1 sec. between these two group means, 6.79 vs 5.06, respectively, was significant, implying that, while wearing contact lenses improved visual efficiency, it adversely affected reading speed. Further, other tasks involving rapid scanning such as scanning the roadway ahead while driving might similarly be affected. PMID- 7870504 TI - Primary teachers' classroom practices and their perceptions of children's attention problems. AB - 15 teachers of Kindergarten through Grade 2 in two schools from a rural southeastern United States community completed the Philosophy of Teaching Scale and indicated on the Child Behavior Checklist their perceptions of 309 children in their classrooms who might show problems of attention. A difference was found between teachers of structured and unstructured orientations in the number of children they reported to be hyperactive. The former group perceived significantly more children in their classroom to be hyperactive. PMID- 7870505 TI - Ultradian rhythms in task performance, self-evaluation, and EEG activity. AB - Many studies have shown the existence of cycles of approximately 90 to 100 minutes (corresponding to Kleitman's basic rest-activity cycle) and several hours ('slow ultradian rhythm' cycles). EEG power spectra, mood, performance, and self evaluation of performance were measured every 15 minutes for 9 hours for 10 male university students. Principal component analysis was applied to extracted ultradian fluctuations in EEG activity, task performance, and the subjective variables. The analysis indicated that two common temporal fluctuations were present, one in the behavioral and subjective variables, and the other in EEG activity. Spectral analysis indicated that the former fluctuated at a rate of 12 cycles per day (corresponding to basic rest-activity cycle), and the latter was comprised of both a slower (6 cycles per day) and a faster (10 to 18 cycles per day) cycle, thereby supporting the multioscillator hypothesis of ultradian rhythm. PMID- 7870506 TI - Drawing designs from memory in dementia. PMID- 7870507 TI - Inner speech and respiration: toward a possible mechanism of stress reduction. AB - Stress reduction associated with slow, deep, regular, diaphragmatic-abdominal respiration has been attributed to arousal reduction and to diversionary effects on the cognitive mediation of stress. Evidence was presented to show that verbal inner speech, self-talk, is a primary cognitive mediator of stress and that inner speech is associated with speech musculature and irregular respiratory movements similar to those of external speech. It was proposed that, if with inner speech one uses and regulates speech musculature and irregular respiratory movements like external speech, then slow, deep, regular, diaphragmatic abdominal respiration may be incompatible with inner speech and may reduce stress by inhibiting stressful self-talk. In addition to describing a stress-reduction mechanism, a potential stress mechanism was suggested wherein fast, shallow, irregular, thoracic breathing and tension of speech musculature associated with stressful self-talk may promote the continuation of stressful self-talk. PMID- 7870508 TI - Relation of preference for location with scores on anxiety and on visibility in golf practice. AB - Previous research has indicated that seating preference in classrooms is related to some personal characteristics. Similar relations are assumed to be found in sports settings. In this study, the associations of rated preference for playing location in group practice of golf with trait anxiety and preference for visibility were investigated. Subjects were 165 Japanese university students who participated in a series of golf lessons. One-factor analyses of variance showed that subjects' rated preference for playing location was significantly related to their scores on trait anxiety and their preference for visibility of location. These results suggest that, in sports practice as in classrooms, preference for location may be associated with measures of personality and visibility. PMID- 7870510 TI - Figural characteristics associated with random appearance of dot patterns. AB - 43 subjects judged the amount of visual randomness of dot patterns in two experiments. The properties of stimuli were changed from Exp. 1 to Exp. 2, but the common characteristics associated with visual randomness were found. PMID- 7870509 TI - Promoting ambulation and object manipulation in persons with multiple handicaps through the use of a robot. AB - A robot was used with a man and a woman affected by blindness, motor disabilities, and mental retardation. The robot was to assist these subjects during their ambulation and allow them to reach a couch (on which to sit) and to transport objects. The data showed that both subjects learned to use the robot, succeeded in transporting and putting away objects, and achieved independent ambulation times of over 22 and 20 min. per session. Staff personnel found the situation in which the subjects were busy with the robot preferable to situations in which the robot was not available. PMID- 7870511 TI - Changes in maternal attitudes and perceptions and children's communication skills. AB - The present investigation had two purposes: (a) to assess significant changes in the attitudes and perceptions of mothers of young children who were enrolled in 15 wk. of individual speech-language therapy and (b) to compare changes in mothers' attitudes and perceptions with university supervisors' ratings of children's over-all communication skills and speech intelligibility. 17 children, ages 2;10 to 5;8, and their mothers were participants. Mothers received speech language services and counseling from graduate-student clinicians and university clinical supervisors but no special counseling was provided to alter their attitudes and perceptions concerning the intervention process. The typical child in the intervention program received 24 individual speech and language therapy sessions. Mothers and supervisors completed questionnaires before and after the 15-wk. intervention. Neither group was made aware of the purpose of the investigation. Analysis showed a pattern of significant changes in mothers' pre- and postrankings of questionnaire items and significant changes in the total communication and speech intelligibility rankings made by supervisors. Significant relationships were found for changes in attitudes and perceptions of mothers and changes in the children's communication skills. The results bolster the need for use of family-based therapy approaches in intervention programs for young children's communication disorders. PMID- 7870512 TI - Time-series studies of the murder and homicide rates in the USA. PMID- 7870513 TI - Directional biases in adults' performance on a multiple-choice water-level task. AB - Performance data on the water-level task were collected on a multiple-choice test requiring 417 adult subjects to choose the one item that represented the waterline of still water in a tilted vessel. Except for the item showing the waterline horizontal, waterlines were drawn oriented +/- 8 degrees, +/- 16 degrees, +/- 24 degrees, and +/- 32 degrees referenced to the horizontal. Analyses of errors from 284 subjects who did not achieve a perfect test score showed that 73% of all errors were made on negatively signed items. Further, among subjects who erred on all trials (n = 128), the majority were remarkably systematic in making their errors, consistently (six out of six trials) choosing items with a negative sign (56%) or items with a positive sign (13%). The predominant negative directional bias suggests that most adult subjects who completely lack an adequate understanding of the invariant horizontality of water were basing their choices on the belief that water tends to climb obliquely towards the brim of the tilted vessel. PMID- 7870514 TI - Reductio ad absurdum: a formal analysis of Rorschach autisms. AB - Generalizing from the rationales underlying the scoring of the three types of Rorschach autisms included in the TRAUT system, it was shown that all perceptual autisms can be subsumed under a single, all-encompassing principle based upon a reductio ad absurdum argument. Therefore, in a way, autisms can be viewed as "cheating," i.e., getting around the explicit and implicit rules governing the evaluation of Rorschach percepts. PMID- 7870515 TI - Burnout of teachers as related to influence tactics within the college classroom. AB - Previous research has shown that burnout among college teachers is negatively associated with on-task learning and student-oriented concerns expressed as tactics on influence in class. Using data collected from 142 college teachers, this study examined this relationship. Burnout was measured on Cherniss's measure, and tactics of influence were assessed by the Behavior Alteration Message Technique. Analysis indicated burnout in teachers was positively related to pressure and position tactics on influence and negatively related to exchange of rewards, rational arguments, and feedback tactics of influence. PMID- 7870516 TI - The young male peak in different categories of trauma victims. AB - The gender distribution of 246,277 trauma patients was investigated for 9 different categories of accidents. For all categories, a young male peak was observed for the 20-29-yr.-olds. Until the age of 59 years, prevalence of men was clear for all types of accidents. After the age of 60 a reversal to prevalence of women was observed for accidental falls. PMID- 7870517 TI - The KoWa model: metric relations in geometric optical illusions. AB - The KoWa model described here gives a parametric account of the geometric conditions for 6 optical illusions from which prediction of illusory qualities of the figures in perceptual judgements may be accomplished using selected stimulus dimensions. The model is designed to allow integration of visual information. PMID- 7870518 TI - Emotional reactions to music by gender, age, and expertise. AB - Fragments of classical music were submitted to 80 subjects, 40 children 9 to 10 years old and 40 adults 19 to 29 years old who were divided into eight groups of ten, to induce feelings of happiness, sadness, anger, and fear. The task required linking each piece of music to one emotion, identifying at the same time the intensity of the emotional response on a scale of 1 to 3. The goal was to study how gender, age, and exposure or expertise related to emotional perceptions of music. Analysis showed (a) experts in music and nonexperts ascribed similar emotions to pieces of music, (b) there was no difference in emotional response to music by gender, although women linked to music stronger emotions of anger than girls, (c) children perceived greater feeling of happiness in music and less feeling of anger than adults, and (d) emotions of anger and fear in music were often confused with one another. PMID- 7870519 TI - Use of a timeout ribbon with and without consequences as procedures to improve a child's compliance. AB - The purpose of the present case study was to evaluate use of a timeout ribbon with and without student-selected consequences on the compliance of a preschool student with disabilities. An ABACBC single-subject replication design was used. Compliance was low during the first baseline condition. When the timeout ribbon procedure was implemented in the classroom, compliance increased, but a return to baseline produced low compliance. When consequences were added to the timeout ribbon procedure, the child's compliance improved further. Additional replications of timeout ribbon and the timeout ribbon plus consequences generated less and less compliance. Possible reasons for the lack of robust findings were discussed. PMID- 7870520 TI - Rasch partial credit analysis of gross motor competence. AB - The purpose of this study was to introduce a model for measurement of partial credit for the assessment of gross motor competence. Four different striking tasks were administered to a total of 128 children, ages 3 to 9 years, consisting of 64 boys and 64 girls. The partial scores were analyzed using the Rasch Partial Credit model. Satisfactory fit of model and data was obtained for Task 1 and Task 4. Step difficulties estimated for Tasks 1 and 4 ranged from 5.61 to 5.50. The average ability of the children was 0.09 (SD = 2.95). The first and second steps of Tasks 1 and 4 were easy for the children and the fourth step was difficult for them. The major advantage of using the Rasch Partial Credit analysis is that motor process measures can be calibrated and analyzed by a quantitative model with advanced test characteristics. PMID- 7870522 TI - Hypnosis in sport: an Isomorphic Model. AB - Hypnosis in sport can be applied according to an Isomorphic Model. Active-alert hypnosis is induced before or during practice whereas traditional hypnosis is induced after practice to establish connections between the two experiences. The fundamental goals are to (a) develop mental skills important to both motor and hypnotic performance, (b) supply a wide range of motor and hypnotic bodily experiences important to performance, and (c) induce alert hypnosis before or during performance. The model is based on the assumption that hypnosis and motor performance share common skills modifiable through training. Similarities between hypnosis and peak performance in the model are also considered. Some predictions are important from theoretical and practical points of view. PMID- 7870521 TI - Use of firearms for suicide in Canada. PMID- 7870523 TI - Suicide rates in cohorts over time in Denmark. PMID- 7870524 TI - Suicide in immigrant groups as a function of their proportion in the country. PMID- 7870525 TI - Impending electrical shock can affect response force in a simple reaction task. AB - For 20 subjects reaction times and force of response were measured on a simple reaction time task to visual stimuli while activation was manipulated by occasionally delivering a noninformative electrical shock. In blocks in which shocks were delivered, forces of response were larger than those in control blocks without shocks. The results are discussed in terms of Sanders' model of stress. PMID- 7870526 TI - Studying complex decision making in natural settings: using a head-mounted video camera to study competitive orienteering. AB - Head-mounted video recording is described as a potentially powerful method for studying decision making in natural settings. Most alternative data-collection procedures are intrusive and disruptive of the decision-making processes involved while conventional video-recording procedures are either impractical or impossible. As a severe test of the robustness of the methodology we studied the decision making of 6 experienced orienteers who carried a head-mounted light weight video camera as they navigated, running as fast as possible, around a set of control points in a forest. Use of the Wilcoxon matched-pairs signed-ranks test indicated that compared with free recall, video-assisted recall evoked (a) significantly greater experiential immersion in the recall, (b) significantly more specific recollections of navigation-related thoughts and feelings, (c) significantly more realizations of map and terrain features and aspects of running speed which were not noticed at the time of actual competition, and (d) significantly greater insight into specific navigational errors and the intrusion of distracting thoughts into the decision-making process. Potential applications of the technique in (a) the environments of emergency services, (b) therapeutic contexts, (c) education and training, and (d) sports psychology are discussed. PMID- 7870527 TI - Numerosity estimation and age. PMID- 7870528 TI - Markers of cerebral lateralization and alcoholism. AB - We assessed markers of anomalous cerebral dominance in 70 problem drinkers at risk for alcoholism, 43 alcoholics who had been sober for at least six months, and 311 healthy control subjects age-matched to the problem drinkers. Markers of anomalous cerebral dominance included left-handedness, learning disabilities, neuro-immune disorders, and special cognitive talents. We also administered a "drinking inventory" to assess frequency and severity of drinking patterns for self and family. Analysis showed elevated rates of left-handedness and learning disabilities in the alcoholic group and in the "at risk" problem drinkers. These same subjects rated themselves and their families as relatively poor at left hemisphere-mediated cognitive talents. Alcoholic women evidenced significantly greater incidence of immune disorders than alcoholic men. Alcoholism appears to be related to biological factors which have been associated with anomalous cerebral dominance. PMID- 7870529 TI - Induced motion and the visual vertical: effects of frame size. AB - Induced visual motion and the rod-and-frame effect have both been explained in terms of changes in the observer's spatial orientation. Accordingly, we examined the effects of large and small visual frames on the two phenomena in the present experiment, testing 8 male and 8 female undergraduates. During induced motion, subjects noted the perceived motion of a stationary central point of light and then moved this light back to its apparent original location. For the visual vertical, subjects aligned two points of light to indicate the perceived vertical in the presence of straight and tilted frames. As predicted, the larger frames generated more induced motion and greater displacement of the visual vertical. These results may have occurred because the larger frame had a greater effect on the subjects' spatial orientation, perhaps due to the more extensive involvement of the peripheral, or ambient, visual system. PMID- 7870530 TI - CERT: a perceived exertion scale for young children. AB - This paper describes the rationale for the Children's Effort Rating Table (CERT) designed for assessing perceived exertion by children aged 6 to 9 years. This device is similar to Borg's Rating of Perceived Exertion (RPE) which is internationally recognized and currently used in conjunction with standard metabolic measures in a wide range of settings where exercise is prescribed and the intensity of various forms of physical activity is regulated by adults. We devised CERT for use in our research on the development of perception of effort by younger children. Some validation research on CERT has been completed. PMID- 7870531 TI - Stimulus-response compatibility in a small sample of cerebral palsied adults. AB - Stimulus-response compatibility refers to the correspondence between a sensory event and the motor response which it specifies. A discrete aimed movement task with two conditions of stimulus-response compatibility tested whether higher compatibility would decrease the reaction time of 5 subjects with normal movement and 6 subjects with cerebral palsy. A board with 3 distances (13.5, 28.0, 40.5 cm) along each of 3 rays (45 degrees, 90 degrees, 135 degrees) provided 9 target sites for a detachable leaf switch. A light on the switch was turned off or on for the low or high compatibility condition. The independent variables were the Index of Difficulty, target position and compatibility. The dependent variables were reaction time and movement time. The reaction times for both groups were less during the high compatibility condition than during the low compatibility condition as shown by a t test for differences between means. Multiple regression analyses showed that reaction time of the normal group was a positive linear function of compatibility and movement time was a positive linear function of the Index of Difficulty for both groups and of position for the normal group, 3 normal subjects and 2 cerebral palsied subjects. There were indications of ballistic rather than aimed movements. The results are discussed with regard to the role of visual fixation in aimed movement, the similarities between groups in conformance to Fitts' Law and differences between groups in reaction and movement times. PMID- 7870532 TI - Imitative suicide in a cohesive organization: observations from a case study. AB - Three suicides occurred within 3 years in a military unit of 35 individuals. This represented an annual rate 220 times the North American average. A clinical intervention was requested by medical authorities, the goal being to minimize the risk of further deaths. Group and individual therapy was conducted over 3 days and ongoing referrals were made as necessary. In addition, measures of anxiety, depression, and hostility were obtained from this unit and from a unit equivalent in size and job description to examine whether these constructs could be used diagnostically. Analysis of the data indicated that differences in mean scores between the units yielded potentially misleading information, although on an individual basis scores were useful in identifying clients at risk of suicide. When those who personally knew one or more of the decreased were compared with those who did not, variability of scores in conjunction with interviews was helpful in identifying relatively high-risk subgroups. PMID- 7870533 TI - Visuospatial attentional shifts and choice responses of adults and ADHD and non ADHD children. AB - 18 adults, 17 ADHD children, and 18 non-ADHD children performed a choice-response task on which the spatial location of a target was sometimes compatible and sometimes incompatible with priming cues that varied between 50 and 1000 msec. Children's response latencies differed from adults' response latencies as a function of the delay between priming cue and target onset. A cost-benefit analysis indicated that valid stimulus cues facilitated performance and invalid stimulus cues impeded performance similarly for the three groups. Choice-response errors following invalid cues did not differ between ADHD and non-ADHD children; however, adults made more choice errors than children at 150-msec. and 300-msec. delay intervals. Developmental factors that may underlie differences between children's and adults' response speed and response accuracy are discussed. PMID- 7870534 TI - Timing of coincidence anticipation by NCAA division I softball athletes. AB - After visual screening, 44 NCAA Division I softball athletes qualified to participate in this study conducted at the 1993 National Invitational Championship Tournament to assess anticipation of coincidence of these athletes. A full-swing batting motion was used to intercept a stimulus apparently moving at 45 or 70 mph, using the Bassin Anticipation Timer. Scores were recorded as early or late after each subject swung a standardized bat which interrupted a photoelectric beam when each of 20 randomly administered slow or fast simulated pitches was presented. Analyses of variance of AE, CE, and VE showed athletes swung significantly early on the 45-mph and late on the 70-mph simulated pitch speed. More specifically, less AE and CE error was recorded at the slow speed; athletes were more consistent (VE) in response to the fast speed. Results supported prior findings in which simulated-pitch speeds were similar to the present ones. Runway length, simulated-pitch speed, and the degree of swing simulation were suggested as variables to consider in similar investigations. PMID- 7870535 TI - Can suicidologists distinguish between suicide notes from completers and attempters? PMID- 7870536 TI - Forced single-nostril breathing and cognition. AB - This experiment investigated whether forced single-nostril breathing differentially affects cognitive abilities presumed to be mediated by the left and right cerebral hemispheres. Phase I was an attempted replication of a reported sex difference in the effects of unilateral breathing on verbal versus spatial performance and Phase II was a study of breathing effects on different verbal and spatial tests. No differences associated with breathing condition were found in the replication study. In Phase II, men breathing through the right nostril scored significantly lower than men in the control condition on a letter matching test although they did not differ significantly from men in the left nostril condition on that test. There were no significant breathing-related differences on two spatial tests, and no differences associated with breathing condition for the women. Assessment of nostril dominance before and after cognitive testing showed that the forced-breathing exercise did not significantly alter subjects' nostril dominance. A significant left-nostril bias was found in this sample. PMID- 7870537 TI - Motivational effects of anxiety on psychomotor performance. AB - The Hull-Spence theory of anxiety drive (A) was tested in a psychomotor learning situation in which both correct responses (R+) and competing responses (R-) were evoked by the task. Measures of A-Trait and A-State were obtained from 151 women and 52 men, all of whom were then exposed to a sequence of 16 trials on a mirror tracking task presented either continuously or with 2-min. intertrial intervals. Analyses of the effects of A were then performed on samples of 68 women and 16 men drawn from the tails of the A distributions. Theoretical predictions about the effects of A on initial scores and performance trends of both R+ and R- were strongly supported, somewhat more so within the A-State classification than within the A-Trait classification owing to the larger amount of variance accounted for. Analyses involving intermediate levels of A showed that R+ was a monotonic and essentially linear function of A. PMID- 7870538 TI - Grip strength in end stage renal disease. AB - The grip strength of 110 patients with end stage renal disease was measured. Their grip strength tended to be low compared with published norms. Significant correlations were found between the patients' grip strength and their gender, height, weight, and diabetic status. A regression equation including gender, height, and diabetic status as independent variables explained more than 40% of the variance in patients' grip strength. PMID- 7870539 TI - Elevated incidence of a sensed presence and sexual arousal during partial sensory deprivation and sensitivity to hypnosis: implications for hemisphericity and gender differences. AB - As predicted by the vectorial cerebral hemisphericity hypothesis, 24 normal young women reported significantly more experiences of a "presence" than did 24 normal young men within a setting that emphasized hypnosis and partial sensory deprivation. The incidence of these experiences was positively correlated with scores on Spiegel's Hypnosis Induction Profile, while the attribution of the chamber experiences to ego-alien sources was correlated with the magnitude of (Vingiano's) right hemisphericity for the women only. Both sexes exhibited a significant association between the experience of a presence and sexual arousal. PMID- 7870540 TI - Effect of cognitive style on test type (visual or verbal) and color coding. AB - 66 field-independent undergraduates achieved significantly higher scores than 43 field-dependent students on drawing, terminology, and comprehension. Color coding was an inconclusive instructional variable, but unexpectedly, subjects who received the verbal tests scored significantly better than those who received the visual test format. PMID- 7870542 TI - The Holinger/Easterlin cohort hypothesis about youth suicide and homicide rates. PMID- 7870541 TI - Superiority of clear-visor safety hat to opaque-visor hat: an evaluation of upper visual-field obstruction. AB - Three subjects were used to compare superior visual-field threshold for 5 North American industry-standard opaque safety hard hats with a prototype clear translucent-visor safety hard hat and a no-hat baseline condition. Average maximum degrees of superior visual field was equivalent for the clear-visor safety hat and no-hat conditions (52.0 degrees versus 48.3 degrees) but the opaque-visor safety hats resulted in only 15.1 degrees. The opaque safety hats were worse than the clear-visor safety hat and no-hat conditions by, on the average, an order of 3. Analysis indicated that visual-field obstruction is a potential problem for wearers of opaque safety hats. Field research will be required to assess the extent of injuries caused by an impaired superior field of vision when wearing opaque-safety-hat visors. The potential positive effects of the clear-visor safety hat on reduction of accidents also must be determined. PMID- 7870543 TI - Corsi's block-tapping test: standardization and concurrent validity with WISC-R for children aged 11 to 16. AB - Corsi's block-tapping test and WISC-R were given to 1122 children from 11 to 16 years of age. Corsi's raw scores were transformed into standard scores like those for the WISC-R subtests. Reliabilities, standard score equivalents of raw scores, correlations with scores on WISC-R subtests, scales and factor scores are presented. A Principal Factor analysis of intercorrelations for Corsi's test and WISC-R subtests shows a three-factor solution with Corsi's test loading on the Third Factor. Results agree with Wielkiewicz's (1990) hypothesis about the construct underlying WISC-R Third Factor as "executive" and short-term memory processes. PMID- 7870544 TI - Examining the Luscher Color Test. AB - 98 subjects rated the 8 colored cards from the Luscher Color Test from their most to least preferred colors. Luscher claimed subjects who select identical color combinations have similar personalities. Statements were formed from Luscher's descriptors of personalities while ensuring that the social desirability of the statements was equal. Subjects were asked to state the extent to which their personalities matched the descriptive statements. Luscher suggested that people who favor red and yellow are more extraverted than those who prefer blue and green, but the data did not support Luscher's predictions. Color preference was not related to self-descriptions when social desirability was controlled. Moreover, people favoring green and blue were not more introverted than those favoring red or yellow. PMID- 7870545 TI - Time estimation and juvenile delinquency. AB - Certain empirical evidence suggests that subjects prone to delinquent activity may have faster internal clocks than others. To investigate the relationship between antisocial behavior and time perception and its dependence on the experimental time interval and method and on whether the subject is institutionalized we obtained verbal and production estimates of 5-, 15-, 30-, and 60-sec. intervals from 249 adolescents (156 school attenders and 93 institutionalized subjects) classified into 3 groups according to the intensity of their antisocial activity. Results provide no support for the hypothesis that overestimation of short time intervals is associated with either juvenile delinquency or institutionalization. PMID- 7870546 TI - Predicting risk-reducing occupational AIDS behaviors in a sample of emergency medical personnel. PMID- 7870547 TI - Quantitative electroencephalographic validation of left and right temporal lobe signs and indicators in normal people. AB - During a single 20-min. exposure to partial sensory deprivation, the average duration of alpha rhythms over the left temporal lobe (T3) increased significantly compared to that for the right homologous region (T4). The percentage changes (increase) over time in the duration of alpha rhythms over the left temporal lobe but not the right temporal lobe were significantly correlated (.64) with histories of automatic behaviors (cessation of awareness) while only the relative increases over time in the durations of alpha rhythms over the right temporal lobe were correlated with histories of vestibular-auditory experiences (.42). The results suggest construct validity for differential hemispheric sources of some specific clusters of complex partial epileptic-like experiences that have been inferred to reflect the continuum of temporal lobe lability. PMID- 7870548 TI - Motor skill acquisition, auditory distractors, and the encoding specificity hypothesis. AB - 28 women and 28 men threw a paddleball at a target in 4 conditions of noise and quiet, being given 150 trials on 2 days. Analysis of absolute constant error and total error indicated the encoding-specificity hypothesis was not supported and no transfer was noted across conditions, perhaps because the noise was not demanding enough. PMID- 7870549 TI - What's causing the pain?: a re-examination of the Aikido Nikyo technique. AB - Recently there have been several investigations into the etiology of the pain produced on the application of Aikido's Nikyo (Second-teaching). This paper analyzes several conclusions as to the discrepancies found in the results of these studies. PMID- 7870550 TI - Vowel use of phonologically disordered identical twin boys: a case study. AB - Very little is known about the vowel systems of phonologically disordered children. This study provides longitudinal data regarding vowel use of identical twin boys between the ages of 3;5 and 4;9. The boys were identified as phonologically disordered; however, their parents chose not to enroll them in therapy. Vowel-use information was taken from spontaneous language samples. It was discovered that initially their phonological disorder also affected their vowel systems, but as their phonological skills increased so did correct use of vowels and their vowel use tended to follow normal developmental trends. PMID- 7870551 TI - Empathy and adolescent male sex-offenders. AB - This study provides data on empathy for 82 adolescent male sex-offenders and 108 male nonoffenders. No statistically significant association was found between scores on a 4-item measure of empathy and sex-offender status. PMID- 7870552 TI - Analysis of eyeblink activity during discriminative tasks. AB - To evaluate the blinking pattern during and after cognitive processing, 10 subjects' eyeblinks were recorded by a videotape recording camera placed 100 cm from the subjects' side. The subjects' task was to discriminate two kinds of auditory tones presented serially and to discriminate two kinds of visual stimuli presented serially. Treatments were composed of the baseline condition preexperiment, the visual task with no discrimination, the visual discriminative task, the auditory task with no discrimination, and the auditory discriminative task. The blink rate in each treatment, the temporal distribution of blinks poststimulus, and the blink waveform were evaluated. Although blinks were not inhibited during tasks, frequent blinks after tasks were observed in both modalities. Blinks concentrated between 300 msec. and 800 msec. after the discriminated stimulus and formulated the blink-rate peak. The closing velocity of lid in the blink rate peak was lower after auditory stimulus. Moreover, the lid's opening velocity after the auditory discrimination was higher. These results indicated that the eyelid closed slowly and opened quickly after the auditory discriminative stimulus. PMID- 7870553 TI - Digital skin temperature and biofeedback. AB - The present study simultaneously compared the skin temperature of the index and the little fingers during hand warming using biofeedback. There was a 5-min. baseline recording followed by a 10-min. session during which subjects attempted to increase skin temperature using the index finger with biofeedback in the form of lights and sound. Analysis showed no significant differences between the temperatures of the index and of the little fingers, but there was a significant increase in temperature during the session for both sites. PMID- 7870554 TI - Handedness and dyslexia: a meta-analysis. AB - The question whether there is an association between handedness and dyslexia has been investigated in many studies spanning more than 50 years. In 1990, Bishop reviewed studies which met stringent methodological criteria and concluded that there was little support for an association. A reanalysis of the same studies using newer procedures of meta-analysis shows that there is a small but reliable increase in the proportion of nonright-handers among dyslexics as expected by the right-shift theory of handedness of Annett. PMID- 7870555 TI - Locus of control differences among stress groups. AB - To assess among 3 groups differing in stress significance of differences in their scores on locus of control scales (Internal, Powerful Others, and Chance), 2 groups of college undergraduates (123 and 160 subjects) were tested. In both samples analysis indicated significant differences among the 3 groups in scores on the Powerful Others and Chance (external) scales, with the severely stressed group scoring higher than the milder stress groups. No significant differences were found on the Internality scale. PMID- 7870556 TI - Preliminary study of the bilingual version of the self-actualization value subscale of the Personal Orientation Inventory. AB - A bilingual version of Shostrom's Self-actualization Value subscale of the Personal Orientation Inventory was administered to 62 Malaysian students. For the 26-item paired-opposite inventory, test-retest reliability over 6 mo. was .39 (for boys .42, for girls .37) and criterion validity was .57. Replication with other groups is recommended. PMID- 7870557 TI - Comparison of error rates and performance on Wechsler's Coding and Digit Symbol subtests and the Symbol-Symbol test for children and adults. AB - Performance on Digit Symbol, Coding, and similar symbol-substitution tests are known to be influenced by a wide variety of reversible and nonreversible organic syndromes and learning disabilities. Recently, questions regarding the interchangeability of different symbol-substitution tests have been raised. The present study compared the performance, i.e., number of substitutions completed accurately and number of errors, of 37 adults, 32 adolescents, and 45 children on the Wechsler symbol-substitution tests of Digit Symbol and Coding with their performance on the recently designed Symbol-Symbol test. Analysis indicated that, while Symbol-Symbol performance is highly correlated with Wechsler scores on symbol-substitution tests, significant differences in error rates and speed of performance suggest that the Symbol-Symbol test cannot be considered an equivalent symbol-substitution test. Further investigation of the properties and the potential uses of the Symbol-Symbol test with clinical populations must be undertaken. PMID- 7870558 TI - Psychology of computer use: XXXII. Computer screen-savers as distractors. AB - The differences in performance of 16 male and 16 female undergraduates on three cognitive tasks were investigated in the presence of visual distractors (computer generated dynamic graphic images). These tasks included skilled and unskilled proofreading and listening comprehension. The visually demanding task of proofreading (skilled and unskilled) showed no significant decreases in performance in the distractor conditions. Results showed significant decrements, however, in performance on listening comprehension in at least one of the distractor conditions. PMID- 7870559 TI - Comparative effects of exercise reduction and relaxation training on mood states and Type A scores in habitual aerobic exercisers. AB - The comparative effects of exercise reduction and relaxation training on dysphoric mood states and Type A scores in persons who exercise beyond the American College of Sports Medicine's recommended guidelines for cardiovascular fitness were investigated. Using their scores on the Profile of Mood States and the Jenkins Activity Survey, 57 subjects were randomly divided into 3 matched groups based on age, gender, and exercise regimen. Subjects assigned to the control group maintained their current exercise regimen, those in the second group reduced their exercise regimen to include no more than 5 hours of aerobic activity per week, and those in the third group maintained their current exercise regimen and attended 5 1 1/2-hr. relaxation training sessions. Both inventories were administered again after 10 weeks. Multivariate analysis of covariance showed no statistically significant differences among group means on the dependent variables. Further research on the use of aerobic exercise and relaxation training as auxiliary treatments for anxiety and depression is recommended. PMID- 7870560 TI - Cerebral asymmetry in facial affect perception by women: neuropsychological effects of depressed mood. AB - 40 right-handed women, half of whom had been classified with depressed mood and the other half as nondepressed, participated in a tachistoscopic study of the influence of depressed mood on the cerebral hemispheric processing of Ekman and Friesen's 1976 happy, sad, and neutral emotional faces using a forced-choice reaction-time paradigm with only happy and sad alternatives as response manipulanda. The women with depressed mood were also characterized by elevated scores on both state and trait anxiety, suggestive of an anxious-depressive state with heightened arousal. Primary findings for the tachistoscopic data indicated that women with depressed mood as compared to nondepressed women displayed significantly faster reaction times to sad faces presented in the right visual field and happy faces presented in the left visual field. These results are suggestive of differential arousal of both the left and right cerebral hemispheres in this sample of anxious-depressed women and are discussed in light of arousal theory. PMID- 7870561 TI - Age and gender distributions of pedestrian accidents across the life-span. AB - Causes of pedestrian accidents (N = 534) were investigated for patients treated for injuries at the emergency unit of a hospital. Accidents in collisions with motor vehicles were the main cause (87.8%). Young children (0-9 years old) and the elderly (above 60 years of age) are the most vulnerable in terms of mortality rates observed in these age groups. Preponderance of males in pedestrian accidents was observed in the accident categories of collisions with motor vehicle and bicycle, whereas a slight preponderance of females was found in collisions with other traffic. The predominant age groups were located in the range from 0 through 19 years. PMID- 7870562 TI - Examining the interaction of age x race pertaining to black-white differences at ages 15 to 93 on six Horn abilities assessed by K-FAST, K-SNAP, and KAIT subtests. AB - This study examined differences between black and white subjects on 6 abilities from Horn's Gf-Gc theory for 5 age groups between 15-19 and 55-93 years (total ns = 956 white and 128 black subjects). White respondents scored significantly higher on all 6 abilities, but differences on fluid reasoning and short-term apprehension and retrieval were less than .5 SD. Interactions of age x race were nonsignificant, indicating that the discrepancies between scores of black and white subjects did not vary as a function of age. PMID- 7870563 TI - Textual criticism. PMID- 7870564 TI - Lightness perception can be affected by surface curvature from stereopsis. AB - It is demonstrated that lightness perception can be affected by shape from stereopsis. The starting point was a report by Knill and Kersten that the perceived lightness of a monocularly viewed surface can be affected by outline contour cues indicating that the surface is three-dimensional (3-D). In that study stimuli consisted of two equally sized abutting regions each having the same vertical linear-intensity ramp, so that the horizontal abutting boundary of the two patches created a sharp change in intensity. When this version of the Craik-O'Brien-Cornsweet stimulus has a rectangular outline, it exhibits the standard simultaneous contrast illusion: equivalent patches in the top and bottom regions appear to have different brightness despite having the same luminance. Knill and Kersten replicated this phenomenon with stimuli whose outline-contour cues were consistent with a flat (planar) surface. They found, however, that the illusion was greatly reduced in stimuli with outlines consistent with two abutting 3-D quarter cylinders, for which equivalent regions in the two halves appeared of similar lightness. Knill and Kersten interpreted this effect in terms of surface-lightness computations that took into account 3-D surface shape to achieve an integrated interpretation of the luminance and shape data. In the present report three experiments are described for which these earlier findings were taken as the starting point. In the first experiment the results were replicated by the use of a different methodology. In the second experiment it was shown that shape-from-stereo can produce similar effects on lightness perception to that caused by shape-from-contour. Real 3-D objects with curved surfaces, luminance profiles of the Knill and Kersten type, and carefully controlled outline-contour cues were used so that the objects appeared flat when viewed monocularly but curved in 3-D when seen binocularly. The third experiment was a control confirming that the stereo effect was not simply due to differences caused by monocular versus binocular viewing. It is concluded that the human visual system uses stereo cues, as well as outline-contour cues, in the interpretation of luminance data to recover surface lightness. PMID- 7870565 TI - Integrating global and local aspects of visual occlusion. AB - The phenomenon of visual occlusion has frequently been studied by means of two dimensional line drawings. These drawings may elicit various interpretations. Sometimes a mosaic of shapes is seen, sometimes a shape that partly occludes another shape. In the latter case, observers often have a clear idea about the form of the partly occluded shape. Local and global pattern aspects both seem to be decisive with respect to the preferred interpretation. An attempt is made to integrate these aspects by applying the global-minimum principle to the perceptual complexity of three distinct components of those pattern interpretations: (i) The internal structure, dealing with each of the shapes separately, (ii) the external structure, dealing with the positional relation between these shapes, and (iii) the virtual structure, dealing with the occluded parts of the shapes. The perceptual complexity of each of these three components can be expressed in terms of structural information. The hypothesis that the perceptually preferred interpretation is the one for which the total information load is minimal is tested on many patterns stemming from different studies on pattern completion. PMID- 7870566 TI - Three-dimensional illusory objects produced by rotation in depth. AB - Rotation of a Kanizsa triangle in depth around its vertical axis causes a perception of a three-dimensional object with a flat, rigid illusory triangle between the inducing discs. When the inducing discs of a Kanizsa triangle were made thicker, the illusory triangle between the discs also became thicker. In the experiments both computer animation and real inducers made of plastic were used. The method promoted border perception in a three-dimensional illusory figure. We suggest that the perception of three-dimensional illusory objects is due to a process which is also used in the perception of real three-dimensional objects. PMID- 7870567 TI - Intraattribute and interattribute motion induction. AB - The phenomenon of motion induction occurs, for example, when a bar that is presented next to a spot, which itself was presented slightly earlier, is not correctly perceived to appear everywhere simultaneously, but seems to grow out of the spot. The spot is said to prime one end of the bar. Experiments have been designed to throw more light on the local and global aspects of this phenomenon, in particular to establish whether this illusory motion percept can be observed when the spot and the bar stimuli are defined with respect to the background by one of a variety of attributes, such as luminance, color, stereodepth (crossed and uncrossed), texture, and motion (start and stop). It was found that all attribute combinations supported motion induction readily, but that the strength of the perceived motion (as measured by magnitude estimation) varied and depended more on the attribute defining the bar than on the attribute of the spot. Luminance and color gave the most vivid effects, whereas motion and depth showed the least vivid effects. The influence of the amount of luminance and color contrast on the strength of the effect was also determined and it was found that these variables affected motion induction most at very low contrast levels close to detection threshold. It is concluded that the illusory motion in this effect depends only slightly on the particular visual attribute channel that carries the stimulus information. This is consistent with the contention that it is a high level, attention-related effect, phenomenologically similar to polarized gamma movement. PMID- 7870568 TI - Spatial reference systems in the comprehension of rotational motion. AB - In certain simple rotations of objects, the orientation of the axis and planes of rotation can determine whether people are able to visualize the motion or perceive it as simple and coherent. This finding affords the opportunity to investigate the spatial reference systems used to define the orientation of the axis and planes of rotation. The results of two experiments suggest that the permanent environment is the primary reference system, apart from the rotating object, used for this purpose. Subjects also were able to use a local spatial environment to determine the orientation of the motion; some subjects were particularly adept at this. The viewer perspective, in contrast, was irrelevant as a reference system in these experiments. These results argue strongly for the primacy of environmental reference systems in the perception and imagination of orientation and extend the set of findings common between the comprehension of rotational motion and orientation-sensitive form perception. PMID- 7870569 TI - Estimation of time to vehicle arrival--effects of age on use of available visual information. AB - Subjects estimated time of vehicle arrival while viewing twenty-four film clips of an approaching vehicle, half with a constant viewing time of 4.2 s and half with a constant vehicle-movement distance of 40 m. The distances from the subject at which the film ended were 20, 60, and 100 m. Speeds of approach varied between 7.45 and 15.44 m s-1. Performance was strongly dependent on age of the subject. Subjects in the 5-6-year-old group made estimates based on the distance of the vehicle; at 7-8 years an interaction between the effects of distance and velocity appeared and for 9-10-year-olds there was a main effect of the vehicle velocity. Only for adults was the information from distance and velocity fully integrated. There was no significant difference between males and females for any of the age groups. Performance of adults was very similar to that reported by other authors in that subjects underestimated the time to arrival of the vehicle, with estimated times about 60% of the actual times. Standard deviations of the estimated times were such that a small percentage of subjects overestimated times and hence would have caused a collision if they had proceeded with a crossing. The mechanism of time estimation was strongly dependent on the angular velocity of the vehicle subtended at the eye of the observer. This must exceed a threshold value of about 0.002 rad s-1 (adults) if a linear relationship between estimated and actual times is to be obtained. PMID- 7870570 TI - Dichoptically viewed colour aftereffects produced by monocular adaptation. AB - Colour aftereffects were observed in dichoptically viewed achromatic striped patterns after a 25 s period of monocular adaptation to an homogeneous coloured field of red, green, or blue. Three test conditions of dichoptic viewing were used. In condition 1, black line patterns were viewed dichoptically on fused white backgrounds. Stimuli used in condition 2 were similar except that they were white line patterns on black backgrounds. Last, condition 3 was realised with the same stimulus patterns utilised in condition 1, except that the mode of dichoptic viewing produced a juxtaposition rather than a fusion of the two white backgrounds containing the line patterns. Some colour aftereffect was obtained for each colour-adaptation condition and in each test condition. It consisted in a negative colour aftereffect (NCA) in the adapted eye (the colour seen was roughly the complementary of the adaptation colour) and/or a positive colour aftereffect (PCA) in the unadapted eye (the colour seen tended rather to be similar in hue to the adaptation colour). In fact, the following four kinds of responses were obtained: (i) two colour aftereffects, one seen by each eye, ie a NCA involving the adapted eye and a PCA involving the unadapted eye; (ii) a NCA involving the adapted eye only; (iii) a PCA involving the unadapted eye only; (iv) no colour aftereffect at all. Results obtained in different test conditions permitted us to assert that both kinds of colour aftereffect could be produced with white patterns on dark backgrounds as well as with black patterns on white backgrounds and did not require binocular fusion of the white backgrounds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870571 TI - Melodic cues for metre. AB - A method of time-series analysis and a time-beating experiment were used to test the structural and perceptual validity of notated metre. Autocorrelation applied to the flow of melodic intervals between notes from thirty fragments of compositions for solo instruments by J S Bach strongly supported the validity of bar length specifications. Time-beating data, obtained with four stimuli from the same set, played in an expressionless mode, and presented under categorically distinct tempos to different subgroups of musically trained subjects, were rather inconsistent with respect to tapped bar lengths. However, taps were most frequently given to the events in the stimuli that corresponded with the first beats according to the score notations. No significant effects of tempo on tapping patterns were observed. The findings are discussed in comparison with other examinations of metre inference from musical compositions. PMID- 7870572 TI - The c-myc protein represses the lambda 5 and TdT initiators. AB - The lambda 5 promoter initiates transcription at multiple sites and confers expression in all cell types. Two lambda 5 promoter-derived oligonucleotides (Inr lambda 5:1 and Inr lambda 5:2), each with a transcription start site, could promote transcription in transient transfection assays. In contrast, a third oligonucleotide (+90 lambda 5), without a transcription initiation site, was inactive. The Inr lambda 5:1 and Inr lambda 5:2 oligonucleotides formed a major DNA-protein complex B' in gel retardation analyses; no protein-DNA complexes were observed with the inactive +90 lambda 5 oligonucleotide. The B' complexes of Inr lambda 5:1 and Inr lambda 5:2 each contained c-myc and myn (murine homologue of Max) proteins. The c-myc and myn proteins were also found to bind the TdT initiator (InrTdT). Using mutated oligonucleotides, we found that the c-myc/myn proteins bound to the transcription initiation site of both Inr lambda 5:1 and InrTdT, however, these mutated oligonucleotides were inactive in transfection assays. This suggested that, in this system, transcription depended both on a transcription initiation site and appropriate flanking sequences. The significance of c-myc binding to the respective initiator was analysed by overexpressing c-myc in co-transfection assays. Under these conditions the transcriptional activity of both the lambda 5 and the TdT initiator was repressed. PMID- 7870573 TI - Transfection of mitochondria: strategy towards a gene therapy of mitochondrial DNA diseases. AB - Successes in classical gene therapies have been achieved by placing a corrected copy of a defective nuclear gene in cells. A similar gene replacement approach for a mutant mitochondrial genome is invariably linked to the use of a yet unavailable mitochondrial transfection vector. Here we show that DNA coupled covalently to a short mitochondrial leader peptide (chimera) can enter mitochondria via the protein import pathway, opening a new way for gene-, antisense-RNA- or antisense-DNA-delivery in molecular therapies. The import behavior of the purified chimera, composed of the amino-terminal leader peptide of the rat ornithine transcarbamylase (OTC) and a double stranded DNA molecule (17 bp or 322 bp), was tested by incubating with coupled and 'energized' rat liver mitochondria in the presence of reticulocyte lysate. The chimera was translocated with a high efficiency into the matrix of mitochondria utilizing the protein import pathway, independent from the size of its passenger DNA. PMID- 7870574 TI - A bacterial methyltransferase M.EcoHK311 requires two proteins for in vitro methylation. AB - The genes encoding EcoHK311 restriction-modification (R-M) system were isolated from a clinically-isolated Escherichia coli strain HK31. The entire R-M system of EcoHK311 is located in a 2.1 kb fragment. R.EcoHK311 is an isoschizomer of Eael which recognizes and cleaves Y decreases GGCCR. M.EcoHK31l consists of two polypeptides alpha and beta with sizes 309 and 176 aa, respectively. Polypeptide beta is encoded within aa, alternative reading frame of polypeptide alpha. All the conserved motifs in mC5-MTases can be found in polypeptide alpha except motif IX which is present in polypeptide beta. Polypeptides alpha and beta were separately synthesized in a T7 promoter controlled over-expression system and in vitro methylation occurred only when the two extracts were mixed and thus confirms that two polypeptides are required for methylation. PMID- 7870575 TI - Human TFIIIA alone is sufficient to prevent nucleosomal repression of a homologous 5S gene. AB - Plasmid DNA harbouring the human 5S rRNA gene was assembled into nucleosomes using either Xenopus S150 extracts or purified core histones in the presence of pectin. In both cases reconstitution of nucleosomes led to a complete repression of transcription. This repression could be efficiently counteracted by preincubating the template DNA with highly purified hTFIIIA which allowed the protein to bind to the ICR of the 5S gene. By using an efficient and well-defined in vitro reconstitution system based on isolated core histones in the presence of pectin, which is devoid of endogenous transcription factors, we demonstrate here for the first time that human TFIIIA alone is sufficient to prevent nucleosomal repression of h5S gene transcription and that additional pol III transcription factors are not required to achieve this effect. Additionally, we investigated the binding of hTFIIIA to a mononucleosome reconstituted on the human 5S gene. DNAse I footprinting experiments reveal that the entire ICR of the human 5S gene is covered by the nucleosome, thereby precluding the subsequent binding of human TFIIIA to the promoter of the 5S gene. PMID- 7870576 TI - Construction of a genomic DNA 'feature map' by sequencing from nested deletions: application to the HLA class I region. AB - We are applying a transposon-based approach for detecting and mapping features of special interest to construct 'feature maps' of currently uncharacterized portions of the human leukocyte antigen (HLA) complex on chromosome 6. Such feature maps should facilitate identifying regions for high resolution analysis. Here we describe the feature mapping of a 35 kb DNA fragment located between the HLA-C and HLA-E loci. This fragment was cloned into a transposon gamma delta based cosmid vector designed for generating nested deletions in vivo. Seventy informative nested deletions extending into the cloned fragment were isolated, and DNA adjacent to the deletion endpoints was sequenced by fluorescent automated technology. These islands of DNA sequences constituted the foundation of the feature map, and (i) identified putative exons, (ii) determined the positions of Alu elements, (iii) determined the span of the keratinocyte-specific S gene, and (iv) localized evolutionarily conserved sequences. The construction of feature maps using this in vivo nested deletion-sequencing approach provides a rapid and efficient means to identify DNA regions that merit more detailed analysis. PMID- 7870577 TI - On the mechanism of preferential incorporation of dAMP at abasic sites in translesional DNA synthesis. Role of proofreading activity of DNA polymerase and thermodynamic characterization of model template-primers containing an abasic site. AB - DNA polymerase preferentially incorporate dAMP opposite abasic sites (A-rule). The mechanism of the A-rule can be studied by analyzing three dissected stages of the reaction including (i) initial nucleotide insertion, (ii) proofreading excision of the inserted nucleotide and (iii) extension of the nascent primer terminus. To assess the role of the stage (ii) in the A-rule, kinetic parameters of the proofreading excision of primer terminus nucleotides opposite abasic sites were determined using E.coli DNA polymerase I Klenow fragment. The relative efficiency of the excision (Vmax/Km) revealed that removal of A was the least favored of the four nucleotides, but the differences in the efficiencies between excision of A and the other nucleotides was less than 2-fold. In addition, in an attempt to reconcile kinetic data associated with the stage (i) or (ii), the differences in free energy changes (delta delta G degrees) for the formation of model template-primer termini containing XN pairs (X = abasic site, N = A, G, C or T) were determined by temperature dependent UV-melting measurements. The order of delta delta G degrees was XG > XA = XC > or = XT, with delta delta G degrees being 0.5 kcal/mol for the most stable XG and the least stable XT. Based on these data, the role of the stage (ii) and energetic aspects of the A-rule are discussed. PMID- 7870578 TI - Characterization of an Arabidopsis thaliana DNA hypomethylation mutant. AB - We have recently isolated two Arabidopsis thaliana DNA hypomethylation mutations, identifying the DDM1 locus, that cause a 70% reduction in genomic 5 methylcytosine levels [1]. Here we describe further phenotypic and biochemical characterization of the ddm1 mutants. ddm1/ddm1 homozygotes exhibited altered leaf shape, increased cauline leaf number, and a delay in the onset of flowering when compared to non-mutant siblings in a segregating population. Our biochemical characterization investigated two possible mechanisms for DNA hypomethylation. In order to see if ddm1 mutations affect DNA methyltransferase function, we compared DNA methyltransferase activities in extracts from wild-type and ddm1 mutant tissues. The ddm1 mutant extracts had as much DNA methyltransferase activity as that of the wild-type for both the CpI and CpNpG substrates suggesting that the DDM1 locus does not encode a DNA methyltransferase. Moreover, the ddm1 mutations did not affect the intracellular level of S-adenosylmethionine, the methyl group donor for DNA methylation. The possibility that the DDM1 gene product functions as a modifier of DNA methylation is discussed. PMID- 7870579 TI - The importance of a single G in the hairpin loop of the iron responsive element (IRE) in ferritin mRNA for structure: an NMR spectroscopy study. AB - Noncoding sequences regulate the function of mRNA and DNA. In animal mRNAs, iron responsive elements (IREs) regulate the synthesis of proteins for iron storage, uptake and red cell heme formation. Folding of the IRE was indicated previously by reactivity with chemical and enzymatic probes. 1H- and 31P-NMR spectra now confirm the IRE folding; an atypical 31P-spectrum, differential accessibility of imino protons to solvents, multiple long-range NOEs and heat stable subdomains were observed. Biphasic hyperchromic transitions occurred (52 and 73 degrees C). A G-C base pair occurs in the hairpin loop (HL) (based on dimethylsulfate, RNAse T1 previously used, and changes in NMR imino proton resonances typical of G-C base pairs after G/A substitution). Mutation of the hairpin loop also decreased temperature stability and changed the 31P-NMR spectrum; regulation and protein (IRP) binding were previously shown to change. Alteration of IRE structure shown by NMR spectroscopy, occurred at temperatures used in studies of IRE function, explaining loss of IRP binding. The effect of the HL mutation on the IRE emphasizes the importance of HL structure in other mRNAs, viral RNAs (e.g. HIV TAR), and ribozymes. PMID- 7870580 TI - Mouse silver mutation is caused by a single base insertion in the putative cytoplasmic domain of Pmel 17. AB - This laboratory has established in previous studies that Pmel 17, a gene expressed specifically in melanocytes, maps near the silver coat color locus (si/si) on mouse chromosome 10. In the current study, we have focused on determining whether or not the si allele carries a mutation in Pmel 17. Pmel 17 cDNA clones, isolated from wild-type and si/si murine melanocyte cDNA libraries, were sequenced and compared. A single nucleotide (A) insertion was found in the putative cytoplasmic tail of the si/si Pmel 17 cDNA clone. This insertion is predicted to alter the last 24 amino acids at the C-terminus. Also predicted is the extension of the Pmel 17 protein by 12 residues because a new termination signal created downstream from the wild-type reading frame. The mutation was confirmed by the sequence of the PCR-amplified genomic region flanking and including the mutation site. The fact that si/si Pmel 17 was not recognized by antibodies directed toward the C-terminal 15 amino acids of wild-type Pmel 17, indicated a defect in this region. We conclude from these results that silver pmel 17 protein has a major defect at the carboxyl terminus. The chromosomal location and the identification of a potentially pathologic mutation in si-Pmel 17 support our conclusion that Pmel 17 is encoded at the silver locus. PMID- 7870581 TI - Fluorescent d(CGCGAATTCGCG): characterization of major groove polarity and study of minor groove interactions through a major groove semantophore conjugate. AB - The major and minor groove in duplex DNA are sites of specific molecular recognition by DNA-binding agents such as proteins, drugs and metal complexes and have functional significance. In view of this, understanding of the inherent differences in their environment and the allosteric information transfer between them induced by DNA-binding agents assumes importance. Site-specific incorporation of 5-aminodansyl-dU, (U*) in oligonucleotides d(CGCGAAU*TCGCG) and d(CGCGAATU*CGCG) leads to fluorogenic nucleic acids, in which the reporter group resides in the major groove. The fluorescent observables from such a probe are used to estimate the dielectric constant of the major groove to be approximately 55D, in comparison to the reported non polar environment of the minor groove (approximately 20D) in poly d[AT]-poly d[AT]. An exclusive minor groove event such as DNA-netropsin association can be quantitatively monitored by fluorescence of the dansyl moiety located in the major groove. This suggests existence of an information network among the two grooves. The fluorescent DNA probes as reported here may have potential applications in the study of structural polymorphisms in DNA, DNA-ligand interactions and triple helix structure. PMID- 7870582 TI - Molecular recognition of tRNA(Pro) by Escherichia coli proline tRNA synthetase in vitro. AB - In this study, we identify a subset of nucleotides that specify aminoacylation of tRNA(Pro) by Escherichia coli proline tRNA synthetase in vitro. Twenty-two tRNA(Pro) variants were prepared by in vitro transcription and their efficiency of aminoacylation with proline (kcat/KM) was measured. From this analysis, we conclude that recognition elements for tRNA(Pro) aminoacylation by ProRS are located in at least three domains of the tRNA molecule. The largest decreases in the kinetic parameters for aminoacylation resulted from single substitutions at position G72 of the acceptor stem and position G36 of the anticodon. Anticodon nucleotide G35 and position A73 in the acceptor stem were also identified as major recognition elements. Moreover, bases that are believed to be important for maintaining the tertiary structure of the tRNA (G15 and C48) appear to be important for efficient recognition of tRNA(Pro) by ProRS in vitro. PMID- 7870583 TI - Ubiquitous mammalian-wide interspersed repeats (MIRs) are molecular fossils from the mesozoic era. AB - Short interspersed elements (SINEs) are ubiquitous in mammalian genomes. Remarkable variety of these repeats among placental orders indicates that most of them amplified in each lineage independently, following mammalian radiation. Here, we present an ancient family of repeats, whose sequence divergence and common occurrence among placental mammals, marsupials and monotremes indicate their amplification during the Mesozoic era. They are called MIRs for abundant Mammalian-wide Interspersed Repeats. With approximately 120,000 copies still detectable in the human genome (0.2-0.3% DNA), MIRs represent a 'fossilized' record of a major genetic event preceding the radiation of placental orders. PMID- 7870584 TI - A kinetic model for subtractive hybridization. AB - Nucleic acid sequences that differ in abundance between two populations (target sequences) can be cloned by multiple rounds of subtractive hybridization and amplification by PCR. These sequences can be cDNAs representing up-regulated mRNAs, or genomic DNAs from deletion mutants. We have derived an equation that describes the recovery of such sequences, and have used this to simulate the outcome of up to 10 rounds of subtractive hybridization and PCR amplification. When the model was tested by comparing its predictions with the published results from genomic and cDNA subtractions, the predictions of the model were generally in good agreement with the published data. We have modelled the outcomes of genomic subtractions, for a variety of genomes, and have used it to compare various strategies for enriching targets. The model predicts that for genomes of less than 5 x 10(8) bp, deletions of as small as 1 kbp should represent > 99% of the DNA after three to six rounds of hybridization (depending on the enrichment procedure). As genomes increase in size, the kinetics of hybridization become an important limiting factor. However, even for genomes as large as 3 x 10(9) bp, it should be possible to isolate deletions of 5 kbp using the appropriate conditions. These simulations suggest that such methods offer a realistic alternative to chromosome walking for identifying genomic deletions for which there are known phenotypes, thereby considerably reducing time and effort. For cDNA subtractive hybridization, the model predicts that after six rounds of hybridization, sequences that do not differ in abundance between the tester and driver populations (the background) will represent < 1% of the subtracted population, and even quite modestly upregulated cDNAs should be successfully enriched. Where several up-regulated cDNAs are present, the predicted final representation is dependent on both the initial abundance and the degree of up regulation. PMID- 7870585 TI - Transient expression in insect cells using a recombinant baculovirus synthesising bacteriophage T7 RNA polymerase. PMID- 7870586 TI - Low stringency-PCR (LS-PCR) allows entirely internally standardized DNA quantitation. PMID- 7870587 TI - Determination of methylation specificity of DsaV methyltransferase by a simple biochemical method. AB - We have developed a simple new method that can identify the base methylated by a sequence-specific DNA methyltransferase and have used it to identify the cytosine that is methylated by DsaV methyltransferase (M. DsaV) within its recognition sequence 5'-CCNGG. The method utilizes the fact that exonuclease III of E. coli does not degrade DNA ends with 3' overhangs and cannot hydrolyze a phosphorothioate linkage. DNA duplexes containing phosphorothioate linkages at specific positions were methylated with M. DsaV in the presence of [methyl-3H] S adenosylmethionine and were subjected to exonuclease III digestion. The pattern of [methyl-3H] dCMP release from the duplexes was consistent with the methylation of the internal cytosine in CCNGG, but not of the outer cytosine. To establish the accuracy of this method, we confirmed the known specificity of EcoRII methyltransferase by the method. We also confirmed the specificity of M. DsaV using an established biochemical method that involves the use of a type IIS restriction enzyme. Methylation of CCWGG (W = A or T) sequences at the internal cytosines is native to E. coli and is not restricted by the modified cytosine restriction (Mcr) systems. Surprisingly, the gene for M. DsaV was significantly restricted by the McrBC system. We interpret this to mean that M. DsaV may occasionally methylate at sequences other than CCNGG or may occasionally methylate the outer cytosine in its recognition sequence. PMID- 7870588 TI - Allele-specific methylation and expression of an imprinted U2af1-rs1 (SP2) gene. AB - The mouse U2af1-rs1(SP2) gene, which was cloned by a two-dimensional genome scanning method, is expressed exclusively from the paternally inherited chromosome. This gene has significant similarity to U2AF and located in chromosome 11, of which maternal duplication/paternal deficiency results in a small body. In this report, we cloned genomic U2af1-rs1(SP2) and found its promoter was methylated in a maternal-allele-specific manner. This allelic methylation was not established in parental gametes, but established between 1.5 d.p.c. and 12.5 d.p.c. on the contrary, the allele-specific expression occurred in the two-cell stage when transcription initiates. Absence of the methylation of the upstream region in this stage indicates that methylation is not necessary for inactivation of the expression. PMID- 7870589 TI - Stability of adriamycin-induced DNA adducts and interstrand crosslinks. AB - The stability of adriamycin-induced DNA adducts and interstrand crosslinks was measured at 37 degrees C by three independent procedures. The loss of [14C] labelled adducts was described by two first-order decays with half-lives of 7.4 h (60% amplitude) and 39 h (40%). The loss of the drug chromophore also exhibited a biphasic character, with half-lives of 6 h (65%) and approximately 150 h (35%). The decay of transcriptional blockages at an isolated, apparent interstrand GpC crosslinking site was described by two first-order processes, with half-lives of 3 h (65%) and 40 h (35%), whereas the decay of transcriptional blockages at an isolated guanine residue (apparent site of monoadduct) was completely described by a first-order decay with a half-life of 5.3 h. The loss of interstrand crosslinks was measured using a gel electrophoresis assay, and the decay was characterised by a single first-order process with a half-life of 4.7 h. Collectively, these values serve to define a model of the interstrand crosslink with unstable sites of attachment at both ends of the crosslink, with half-lives at either end being approximately 5 and 40 h. The adducts exhibited increasing lability with increasing pH, and were particularly unstable at pH 12, with a half life of approximately 0.5 h. The adducts were also heat labile, with an overall melting temperature of 67 degrees C (10 min exposure) and this was also the thermal lability measured at three individual adduct sites probed by lambda exonuclease. PMID- 7870590 TI - Incorporation of 2'-amido-nucleosides in oligodeoxynucleotides and oligoribonucleotides as a model for 2'-linked conjugates. AB - The functionalisation of oligodeoxynucleotides and oligoribonucleotides by incorporation of 2'-amido-2'-deoxyribonucleosides, possibly containing a reporter group via the 2'-amido bond, was examined. Therefore 2'-acetamido-ribonucleosides containing a small methyl group at the 2'-amido bond were synthesized as model compounds. In order to evaluate the influence of this 2'-modification on the hybridization capacities, 2'-acetamido-2'-deoxyuridine was incorporated in both RNA and DNA strands. The suitability of phosphoramidite chemistry for the introduction of this modified nucleoside was proven using laser desorption mass spectrometry of the final oligonucleotide. The presence of the 2'-modification destabilised both RNA-RNA, DNA-DNA and mixed duplexes. Therefore, it can be concluded that the 2'-acetamido group is not a good linker for attachment of reporter groups to oligonucleotides. PMID- 7870591 TI - The actinophage RP3 DNA integrates site-specifically into the putative tRNA(Arg)(AGG) gene of Streptomyces rimosus. AB - The temperate actinophage RP3 integrates site-specifically into the chromosome of Streptomyces rimosus R6-554. The phage attachment site attP and the hybrid attachment sites of the integrated prophage--attL and attR--were cloned and sequenced. The 54nt core sequence, common to all RP3 related attachment sites, comprises the 3' terminal end of a putative tRNA(Arg)(AGG) gene. AttB bears the complete tRNA gene which is restored in attL after integration. A 7.5kb HindIII fragment, bearing attP, was used to construct an integrative plasmid to simulate the integration process in vivo and to localize the phage genes necessary for site specific integration. The int and xis genes were sequenced and compared to other recombination genes. PMID- 7870593 TI - DNA sequence-specific adenine alkylation by the novel antitumor drug tallimustine (FCE 24517), a benzoyl nitrogen mustard derivative of distamycin. AB - FCE 24517, a novel distamycin derivative possessing potent antitumor activity, is under initial clinical investigation in Europe. In spite of the presence of a benzoyl nitrogen mustard group this compound fails to alkylate the N7 position of guanine, the major site of alkylation by conventional nitrogen mustards. Characterisation of DNA-drug adducts revealed only a very low level of adenine adduct formation. Using a modified Maxam-Gilbert sequencing method the consensus sequence for FCE 24517-adenine adduct formation was found to be 5'-TTTTGA-3'. A single base modification in the hexamer completely abolishes the alkylation of adenine. Using a Taq polymerase stop assay alkylations were confirmed at the A present in the hexamer TTTTGA and, in addition, in one out of three TTTTAA sequences present in the plasmid utilized. The sequence specificity of alkylation by FCE 24517 is therefore the most striking yet observed for an alkylating agent of small molecular weight. PMID- 7870592 TI - Identification of two enhancer elements downstream of the human c-myc gene. AB - Expression of the proto-oncogene c-myc is tightly regulated in vivo. Transcription of c-myc is assumed to be controlled by a number of positive and negative cis-acting control elements located upstream or within exon 1 and intron 1. However, these regulatory elements are not sufficient for c-myc expression after stable transfection or in transgenic mice. Transcription of c-myc in vivo thus requires additional control elements located outside the tested HindIII EcoRI gene fragment. In order to identify these putative additional control elements, we mapped DNase I hypersensitive sites around the human c-myc gene in nine different tumor cell lines and in primary lymphocytes. Within the coding and 5' region of the gene, an almost identical pattern of DNase I hypersensitive sites was detected in the various cells. In contrast, chromatin analysis of the c myc 3' region revealed a complex pattern of constitutive and tissue-specific DNase I hypersensitive sites. In enhancer trap experiments we identified two cis acting control elements, both co-localizing with DNase I hypersensitive sites, that stimulated c-myc transcription after transient transfection in Raji or HeLa cells. Both regulatory elements exerted their enhancer activity in either orientation and regardless of their location within the plasmids. Both elements also conferred activation on a heterologous promoter. The association of these enhancers with DNase I hypersensitive sites, indicating their functional activity in vivo, make them potential candidates for the postulated regulatory control element(s) required for c-myc expression in vivo. PMID- 7870594 TI - Endonuclease G from mammalian nuclei is identical to the major endonuclease of mitochondria. AB - Two Mg(2+)-dependent DNA endonucleases have been isolated from mammalian cells which have a strong preference to nick within long tracts of guanine residues in vitro. One endonuclease activity is mitochondrial (mt). The other endonuclease, called Endonuclease G, is associated with isolated nuclei, and is released when the nuclear chromatin is exposed to moderate ionic strength. Our laboratory has previously purified the mt endonuclease to near homogeneity from mitochondria of bovine heart and reported the enzyme to be a homodimer of a approximately 29 kDa polypeptide [Cummings, O. W. et al. (1987) J. Biol. Chem., 262, 2005-2015]. Although the purified mt endonuclease will extensively fragment M13 viral ssDNA and plasmid dsDNAs in vitro, the enzyme displays an unusually strong preference to nick within a (dG)12:(dC)12 sequence tract which resides just upstream from the origin of DNA replication in the mitochondrial genome. The nuclear Endonuclease G first identified from its selective targeting of several (dG)n:(dC)n tracts in vitro (where N = 3-29), was subsequently purified from calf thymus nuclei and shown to be a homodimer of a approximately 26-kDa polypeptide [Cote, J. et al. (1989) J. Biol. Chem., 264, 3301-3310]. In the present study, we find that Endonuclease G partially purified from calf thymus nuclei will extensively degrade both viral ss- and dsDNAs in vitro, and that the enzyme possesses biochemical properties and specificity for nucleotide sequences in DNA that are strongly related or identical to those of the mt endonuclease. These findings and the discovery of sequence identity between the proteins strengthen the conclusion that the nuclear Endonuclease G is the same enzyme as the mt endonuclease. PMID- 7870595 TI - MIRs are classic, tRNA-derived SINEs that amplified before the mammalian radiation. AB - Short Interspersed Nucleotide Elements (SINEs) are highly abundant in mammalian genomes. The term SINE has come to be restricted to short retroposons with internal RNA polymerase III promoter sites in a region derived from a structural RNA (usually a tRNA). Here we describe a novel, 260 bp tRNA-derived SINE, some fragments of which have been noted before to be repetitive in mammalian DNA. Unlike previously reported SINEs, which are restricted to closely related species, copies of this element can be found in all mammalian genomes, including marsupials. It is therefore called MIR for mammalian-wide interspersed repeat. Their high divergence and their presence at orthologous sites in different mammals indicate that MIRs, at least in part, amplified before the mammalian radiation. Next to Alu, MIRs are the most common interspersed repeat in primates with an estimated 300,000 copies still discernible, which account for 1 to 2% of our DNA. Interestingly, a small, central region of MIR appears to be much better conserved in the genomic copies than the rest of the sequence. PMID- 7870596 TI - 21st Symposium on Nucleic Acids Chemistry. Matsuyama, Japan, November 9-11, 1994. Abstracts. PMID- 7870597 TI - Professional development. Anaemia: knowledge for practice (continuing education credit). PMID- 7870598 TI - Ways, but no means. PMID- 7870599 TI - Insecure unit. PMID- 7870601 TI - Double vision. PMID- 7870600 TI - Insecure unit. The nursing view. PMID- 7870602 TI - Developments in the study of familial breast cancer. AB - About 5% of breast cancer may be caused by dominant susceptibility genes, which can be inherited. This would equate to 1250 cases per year in the UK and 9000 in the USA. Even within these cases, there is genetic heterogeneity, meaning there are several genes involved, each giving rise to different patterns of other cancers associated with the familial breast cancer. The identification of these genes will enable the entity of familial breast cancer to be more precisely defined and has implications for management of these breast cancer patients, and their at-risk relatives. The problem with this new area of cancer genetics is that the identification of gene carriers may become possible, and this raises ethical and social issues. PMID- 7870603 TI - Breast cancer. Role of the research nurse. AB - The research nurse in the breast cancer genetics field is a relatively new specialism. This paper explores the role of such a post, including the care of patients at clinics for women at high risk of developing breast cancer. PMID- 7870604 TI - Breast cancer. The family interviewer. AB - In recent years nurses have been employed increasingly as family interviewers for genetic fieldwork. This paper describes some of the work of the author as family interviewer and illustrates how it contributes to the care of high-risk families and to breast cancer genetic research. PMID- 7870605 TI - Making sense of ... the effects of alcohol. PMID- 7870606 TI - Risk-taking for clients with learning disabilities. AB - The following paper examines conditions and influences that precipitate or inhibit risk-taking by nurses working with clients with learning disabilities. Practitioners may experience tensions between facilitating the independence of clients and avoiding negligence. Thus there is an incentive to not allow clients to take many risks. Clients who are denied the dignity of risk lose opportunities to experience ordinary living. More subtly, individuals can also be subjected to services that are relatively benign but also paternalistic. PMID- 7870608 TI - When the motors fail. PMID- 7870607 TI - Complementary medicine. All things considered. PMID- 7870609 TI - Moral obligation. PMID- 7870610 TI - Sports injuries. Fighting for life. PMID- 7870611 TI - Real men get depressed. PMID- 7870612 TI - Who was ... Down? PMID- 7870613 TI - Wound care. A healing regime. PMID- 7870614 TI - Wound care. Sore concerns. PMID- 7870615 TI - Wound care. Diagnosis of leg ulcers. PMID- 7870616 TI - Wound care. Vital ingredients. PMID- 7870617 TI - Cumulative index, volumes 1-17, 1978-1994. PMID- 7870618 TI - Special issue: reference manual 1994-95. American Academy of Pediatric Dentistry. PMID- 7870619 TI - Fumes from the spleen. PMID- 7870620 TI - So what? Under the influence. PMID- 7870621 TI - The value of measuring height and weight of schoolchildren. AB - The measurements of height and weight in the Stockholm school health service was appraised in relation to the screening value, the costs and benefits. The concept of a doubtful screening value of growth surveillances at school age was supported. Investment costs and running expenses were very low. The measurement procedure used only 2% of the total time spent by the nurses in the school health service. The growth data were an appropriate prerequisite for the reassurance of adolescents about their developing identity and body image. The growth data also constituted an appropriate indicator for public heath research. The benefits and low costs may justify maintenance of the measurements in the school health service despite a low screening value. PMID- 7870622 TI - The widening gap in low birthweight rates between extreme social groups in Poland during 1985-90. AB - An attempt was made to identify the reasons for the increase in low birthweight (LBW) rates in Poland from 8.1% in 1985 to 8.4% in 1990. It was found that there was a differential increase in the LBW rates among the social groups. The highest increase was observed among the least educated mothers, especially in large cities. The LBW rate among the newborns of mothers who had finished their education at primary school level increased from 10.6% (in large cities from 14.7%) in 1985 to 12.5% (in large cities to 16.2%) in 1990. Controlling for maternal age, parity, education and place of residence did not change the significance of the increase in the LBW rate. The decline in birthweight was probably largely related to negative changes in socially differentiated levels of consumption of basic nutrients in Poland. PMID- 7870623 TI - Preterm delivery and low birthweight among refugees in Greece. AB - Recently Greece received a large number of refugees mainly from Eastern European countries, Middle East, Africa and the Pontus region. Refugee status, implying psychosocial adversities and financial problems, has traditionally been associated with unfavourable pregnancy outcome. This study aimed to compare the incidence of preterm delivery and low birthweight among 638 refugees and 1231 indigenous women giving birth at the same hospital in Athens. Conditional logistic regression was used in the analysis to account for parity and delivery date (matching variables) as well as controlling explicitly for maternal age and gender of the neonate. It was demonstrated that refugee status did not overall influence the occurrence of preterm delivery or low birthweight, thus implying that these two variables are not sensitive or early indicators of the adverse effects of psychosocial stress suffered by refugees. PMID- 7870624 TI - Impact of induced abortions and statistical definitions on perinatal mortality figures. AB - Two problems originating from the advanced use of medical technology in screening for malformations and in the care of preterm and low birthweight infants are presented: the impact of the increasing number of induced medical abortions and the differences in statistical definitions on perinatal mortality (PNM) figures. Data on 186,562 births registered in the Finnish Medical Birth Registry between 1987 and 1989 were studied, and 65,554 medical abortions (of which 1647 were performed after the sixteenth week of gestation) registered in the Abortion Registry between 1985 and 1990. A 115% increase in abortions for medical reasons in the period 1985-1990 was found. It was estimated that the trend accounted for up to one-third of the decline in PNM rate during that time. The perinatal mortality rate was strongly influenced by very small infants. The application of the Finnish version of the International Classification of Diseases, Ninth Revision (ICD-9) (including all livebirths and using both birthweight of 500 g and gestational age of 22 weeks as the criteria) resulted in PNM rates which were about 5% higher than according to ICD-9. We suggest that the impact of medical abortions on perinatal statistics has reduced the value of the perinatal mortality rate as an indicator of the standard of care. PMID- 7870625 TI - Total bilirubin level in relation to excipients in parenteral morphine sulfate administered to seriously ill newborn infants. AB - We examined exposure to excipients in different morphine sulfate preparations in relation to maximum total bilirubin level during the first 5 days of life among 155 infants admitted to a newborn intensive care unit. Sixty-six (43%), 47 (30%), and 42 (27%) newborns were exposed to chlorobutanol, phenol and neither excipient, respectively. Mean maximum total bilirubin in the first 5 days of life among newborns not exposed to chlorobutanol or phenol was 10.8 mg/dL (184 mumol/L). After adjusting for birthweight, race, sex, and use of phototherapy, the maximum total bilirubin level among newborns exposed to phenol was 1.4 mg/dL (24 mumol/L) higher than the maximum level among newborns exposed to neither excipient (P < 0.05); the corresponding difference associated with chlorobutanol exposure was 1.6 mg/dL (27 mumol/L) (P < 0.02). Further adjustment for potential confounding by the major risk factors for hyperbilirubinaemia did not materially change the results. While unconfirmed, these findings support the growing concern that excipients added to parenteral medications may not be 'inactive' as is often assumed, and that the safety of such exposures in seriously ill newborn infants needs to be studied further. PMID- 7870626 TI - Malformations in children with soft tissue sarcoma and in their parents and siblings. AB - The presence of malformations in a population-based series of 181 children diagnosed with soft tissue sarcoma and in the majority of their parents and siblings was ascertained from family interviews and medical records. Five index children (2.8%) had serious anomalies, a figure not in excess of that derived from general population data. Fourteen siblings (4%) were affected, and higher rates of malformations were seen in siblings of female case children (P = 0.06) and siblings of children with visceral tumours (P = 0.03). There was no correlation between site of tumour in the index and specific organ system anomalies in the index or in their respective siblings. The survey indicated that there are unlikely to be strong associations between childhood soft tissue sarcoma and major malformations, a situation distinct from that found in Wilms' tumour. PMID- 7870627 TI - A population database for maternal and child health research in Western Australia using record linkage. AB - This paper describes a linked total population database established in Western Australia for monitoring and evaluating maternal and child health and for conducting epidemiological studies. Good vital statistics data including all Western Australian hospitalisations and excellent birth defects and cerebral palsy registers have ensured that complete data are available. Examples of studies which have been conducted using the database are given. PMID- 7870628 TI - Measles and absence of Koplik spots in vaccinated children. PMID- 7870629 TI - Further notes on neural tube defects and Chernobyl. PMID- 7870630 TI - Thalidomide--the way forward. PMID- 7870631 TI - Corticosteroids: do they damage the cardiovascular system? AB - Since their introduction for the treatment of rheumatoid arthritis, corticosteroids have become widely used as effective agents in the control of inflammatory diseases. Although there have been undoubted benefits upon mortality in diseases such as systemic lupus erythematosus, many patients survive only to suffer a high incidence of premature atherosclerosis. There is also evidence of increased rates of vascular mortality in other corticosteroid-treated diseases, such as rheumatoid arthritis, reversible airways obstruction and transplant recipients. Possible mechanisms of damage include elevated blood pressure, impaired glucose tolerance, dyslipidaemia, and imbalances in thrombosis and fibrinolysis. This paper reviews the clinical evidence supporting the contention that there is an excess cardiovascular mortality in steroid-treated patients and the underlying mechanisms, and points to further areas of research. PMID- 7870632 TI - Glucose-6-phosphate dehydrogenase deficiency. PMID- 7870633 TI - Orthostatic hypotension and anti-hypertensive therapy in the elderly. AB - The effect of withdrawing or continuing anti-hypertensive therapy on orthostatic blood pressure change in elderly hypertensive subjects was examined. Subjects meeting criteria for therapy withdrawal had supine and standing blood pressure measurements taken on treatment, and at 1, 3, 6, 9 and 12 months off treatment whilst receiving standard non-pharmacological advice to lower blood pressure. Subjects not meeting blood pressure criteria for treatment withdrawal or were unwilling to stop treatment had blood pressure measurements taken after 6 and 12 months whilst also receiving non-pharmacological advice. Orthostatic hypotension was defined as a mean systolic blood pressure fall > or = 20 mmHg on standing from a supine position. Forty-seven subjects (median age 76 years, range 65-84 years) had treatment withdrawn. Thirteen subjects (median age 73 years, range 68 82 years) continued on their treatment. Twelve months after treatment withdrawal there was a significant reduction in the number demonstrating orthostatic hypotension from 11 (23%) to four (11%) (P < 0.05), whilst the group continuing on treatment showed no change. In the withdrawal group those with orthostatic hypotension on treatment (n = 11) were older (79 versus 74 years, P = 0.05), had higher prewithdrawal systolic blood pressure (164 +/- 21 versus 147 +/- 17 mmHg, P = 0.02) compared to those without, although there was no difference in body mass index, gender, number or type of anti-hypertensive drugs taken. In elderly hypertensive subjects withdrawal of anti-hypertensive therapy and institution of non-pharmacological treatment can over several months reduce the prevalence of orthostatic hypotension. PMID- 7870634 TI - Post lumbar puncture discitis and vertebral collapse. AB - Discitis and vertebral collapse are rare but serious complications of lumbar puncture. Clinical profile, management and course of post lumbar puncture discitis in five patients is presented. Such a complication should be kept in mind whenever any invasive procedure is carried out on the spine. PMID- 7870635 TI - Osteomyelitis and infective endocarditis. AB - Osteomyelitis is thought to occur as a complication of infectious endocarditis in as many as 6% of cases of endocarditis. We describe this association in three patients. Osteomyelitis may be difficult to diagnose in patients with endocarditis because symptoms such as fever, bone pain and stiffness are common to both illnesses, therefore physicians need to have a high index of suspicion to avoid missing this important complication. We recommend that patients with endocarditis and persistent or localized musculoskeletal symptoms should be investigated to exclude osteomyelitis. Plain radiographs can be normal in 50% of cases of osteomyelitis in the early stages or show only minor abnormalities, but bone scans are highly sensitive. We suggest that a bone scan is performed if radiography is unhelpful, since a diagnosis of osteomyelitis can effectively be excluded if the bone scan is normal. We advocate close follow-up of these patients with prolonged antibiotic treatment consisting of at least 6 weeks of intravenous therapy, and 3 months or longer of oral therapy. PMID- 7870636 TI - Cyclosporin A in refractory idiopathic nephrotic syndrome: 5 years clinical experience. AB - The use of cyclosporin A (Cy A) in idiopathic nephrotic syndrome, particularly lesions of focal segmental glomerular sclerosis, is controversial. A retrospective study of 10 adult patients with nephrotic syndrome treated with Cy A was performed. Histological diagnosis was established in all patients: focal segmental glomerular sclerosis (n = 6), focal global sclerosis (n = 1), mesangial proliferative glomerulonephritis (n = 1), focal proliferative glomerulonephritis (n = 1) and minimal change disease (n = 1). All patients had previously received immunosuppressive therapy (duration of steroids 1-76 months; 35.0 +/- 12.1, mean +/- SEM). Cy A in a dose of 3-5 mg/kg/day, reduced proteinuria from 16.85 +/- 6.67 to 3.37 +/- 1.48 g/24 hours (P = 0.008), with an associated increase in serum albumin from 15.2 +/- 2.6 to 34.3 +/- 2.5 g/l (P < 0.001). In six patients steroid therapy was discontinued. Cy A was well tolerated for up to 5 years. There was no significant nephrotoxicity. In conclusion, Cy A was effective treatment of refractory idiopathic nephrotic syndrome, including those cases with focal segmental glomerular sclerosis. PMID- 7870637 TI - Effect on central obesity and associated disturbances of low-energy, fruit- and vegetable-enriched prudent diet in north Indians. AB - The effects of fruit and vegetables in conjunction with low-energy diet as adjuncts to a prudent diet were compared for 6 months in a randomized, single blind trial in the management of 202 group A and 204 group B patients with acute myocardial infarction. Dietary intakes were obtained based on weighing of fruit, vegetable and legume intake and weekly diet diaries. After 6 months of follow-up, mean body weight, waist/hip ratio and glucose intolerance fell significantly in patients in group A compared with those in group B. Body weight declined by 5.3 kg in group A versus 2.2 kg in group B (95% confidence interval of difference (CI) 1.28-4.92), waist/hip ratio decreased by 0.05 in group A and 0.02 in group B (95% CI 0.01-0.10), and glucose intolerance decreased by 0.85 mmol/l in group A versus 0.19 mmol/l in group B (95% CI 0.19-1.21). There was a significant net decrease in serum triglycerides (0.18 mmol/l), systolic and diastolic blood pressures (7.9/4.7 mmHg), and a net increase in high-density lipoprotein cholesterol (0.10 mmol/l). Underlying these changes, group A patients had 393 g/day net increase in the consumption of fruit and vegetables and 1,160 kJ/day net decrease in energy intake compared to these changes in groups. Those who made greater changes in diet also had greater improvements in central obesity, glucose intolerance and in other associated disturbances. PMID- 7870638 TI - Guideline for the clinical use and dispensing of thalidomide. PMID- 7870639 TI - Arterial thrombosis in the nephrotic syndrome. AB - Thrombosis is a frequent cause of morbidity and mortality in patients with the nephrotic syndrome. Venous thrombotic complications are well recognized but arterial complications are rare. Thrombosis is multifactorial, and has been attributed to a hypercoaguable state due to alterations in blood levels of the various factors involved in the coagulation and fibrinolytic systems, alterations in platelet function, venous stasis, haemoconcentration, increased blood viscosity and possibly the administration of steroids. Thrombosis in general and arterial thrombosis in particular is a significant and potentially serious problem in nephrotic patients. Awareness of the condition and its pathogenesis is needed. Assessment for the risk factors is required to allow appropriate prophylactic measures to be taken. PMID- 7870640 TI - Unusual cause of orthopnoea: primary tracheal tumour mimicking left ventricular failure. AB - An 84 year old woman who was a heavy smoker presented with clinical features suggestive of acute exacerbation of chronic obstructive lung disease complicated by left ventricular failure. She responded poorly to treatment and then the finding of stridor, only when she was in the supine position, led to the diagnosis of a primary tracheal tumour, a rare but important cause of unexplained shortness of breath. PMID- 7870641 TI - Hypoparathyroidism with extensive intracranial calcification: a case report. AB - We present a case of hypoparathyroidism, demonstrating extensive intracranial calcification, not only in basal ganglia, but also outside the extrapyramidal system. The patient presented with an unexplained epileptifors disorder, accompanied by extrapyramidal dysfunction in the form of choreoathetosis and hemiballismus. Hemiballismus is reported for the first time to our knowledge in association with hypoparathyroidism. PMID- 7870642 TI - Toxic megacolon complicating chemotherapy for acute myeloid leukaemia. AB - A 43 year old woman in remission from acute myeloid leukaemia developed abdominal pain, severe melaena, diarrhoea and gram-negative septicaemia whilst severely pancytopenic following consolidation chemotherapy. Subsequently, serial abdominal X-rays showed a progressive toxic megacolon. Conservative management was attempted but, because of radiological evidence of increasing colonic dilatation and incipient perforation, an emergency defunctioning colostomy was performed. The patient recovered and 2 months later the caecostomy was reversed and a right hemicolectomy performed. This first described case of toxic megacolon following leukaemia treatment is compared with three previously described cases following cytotoxic chemotherapy for other conditions. PMID- 7870644 TI - Acute renal failure with ACE inhibition in aortic coarctation. AB - A 43 year old man with inoperable aortic coarctation and severe hypertension requiring near maximal anti-hypertensive treatment was admitted in severe heart failure. After 2 weeks of treatment the heart failure and blood pressure were incompletely controlled and angiotensin converting enzyme (ACE) inhibitor was started. Serum creatinine was normal before starting the ACE inhibitor and on discharge from hospital. The patient was re-admitted a week later with gross fluid retention and in renal failure. In the absence of alternative causes, a diagnosis of ACE inhibitor-induced renal failure was made and treatment was stopped. The patient required haemodialysis for 2 days and within 1 week the renal function had reverted to normal and has remained so for 1 year. We propose that the renal haemodynamics in severe aortic coarctation are similar to those in bilateral severe renal artery stenosis and advise caution in the use of ACE inhibitors for adults with aortic coarctation. PMID- 7870643 TI - Symptomatic IgG3 deficiency successfully treated with intravenous immunoglobulin therapy. AB - We report the case of a 35 year old female who presented with an 8 year history of repeated upper respiratory tract infection, lymphadenopathy and sinusitis associated with IgG3 deficiency. Courses of monthly intravenous immunoglobulin therapy (0.4 g/kg) resulted in a dramatic clinical improvement on three different occasions. We suggest that investigation of adults with features of immunosuppression, despite normal levels of total IgG, should include IgG3 subclass analysis and that symptomatic patients should be given a trial of immunoglobulin replacement therapy. PMID- 7870645 TI - Primary pelvic hydatid cyst presenting with obstructive uropathy and renal failure. AB - Primary pelvic hydatid cyst is a rare entity. Pelvic hydatid cysts usually present with pressure symptoms involving adjacent organs (bladder and rectum usually). A case of primary pelvic hydatid cyst presenting with obstructive uropathy leading to chronic renal failure is presented. A combination of preoperative albendazole therapy of 1.2 g/day for 8-12 weeks and surgical excision were effective in alleviating the symptoms and improving the renal function. PMID- 7870646 TI - Adenocarcinoma of the duodenum with a duodeno-colic fistula occurring after childhood Wilms' cancer. AB - A case of a 44 year old man with a duodeno-colic fistula secondary to an adenocarcinoma of the second part of the duodenum is described. An asymptomatic leiomyoma of the second part of the duodenum was also present. The patient had been treated successfully for a right Wilms' cancer in childhood with surgery and radiotherapy. There are no previous reports of a duodenal carcinoma arising following a Wilms' tumour and cases of gastrointestinal adenocarcinoma arising as second malignancies following Wilms' tumours are reviewed. The aetiology of duodeno-colic fistulas is reviewed. Duodenal carcinoma is a unusual cause of duodeno-colic fistulas and this case may be unique in that respect. PMID- 7870647 TI - Rhabdomyolysis due to multiple honey bee stings. PMID- 7870648 TI - Response to dietary restrictions in migraine: a comparison of results in children and adults. PMID- 7870649 TI - Barium carbonate, hypokalaemic paralysis and trismus. PMID- 7870650 TI - Herpes zoster encephalitis in the elderly. PMID- 7870651 TI - Acute severe adverse clozapine reaction resembling systemic lupus erythematosus. PMID- 7870652 TI - A state of unlikeness: diversity. PMID- 7870653 TI - Uniting the past and the future in public health nursing: the Michigan Oral History Project. AB - In 1987 a group of Michigan public health nurses recognized the need to capture the richness of the lives of renowned public health leaders by collecting and preserving their oral histories. With the assistance of the Bentley Collection at the University of Michigan, the Michigan Oral History Project found a home. In this paper, the process of designing and implementing the oral history project is described within the framework of McBride's Orchestrating the Stages of a Career, adapted from the Dalton/Thompson/Price career development model. The steps in selecting interviewers and leaders, conducting the interviews, and keeping track of the completed work are outlined. Finally, the early results and potential uses for the collected data are discussed. This project has special significance in this year for the celebration of the centennial of public health nursing. PMID- 7870654 TI - Description of the clinical practice of advanced practice nurses in family centered early intervention in two rural settings. AB - The purpose of this study was to describe the scope of clinical practice of advanced practice nurses who were involved in a project designed to increase access of families with at-risk and disabled young children, newborn to 3 years of age, to early intervention services in rural Washington State. The findings from this study are based on the retrospective review of records of clients seen by the advanced practice nurses. Nursing diagnoses and nursing interventions were assigned to chart recordings. The most frequently occurring nursing diagnoses assigned to parents were Altered Parenting, Altered Family Processes, Fear, Noncompliance, and Knowledge Deficit. The most frequently occurring nursing diagnoses assigned to children were Impaired Physical Mobility, Impaired Verban Communication, Altered Nutrition: Less than Body Requirements, Sensory-Perceptual Alteration, and Altered Thought Processes. Categories of nursing intervention recorded most frequently were Monitoring, Planning and Information. Discussion of findings addresses the roles and reimbursement of advanced practice nurses who provide family-centered early intervention services in rural communities. PMID- 7870655 TI - Family goals as indicants of adaptation during chronic illness. AB - Families that successfully adapt to new situations have been found not only to appraise the situations as manageable but also to possess the necessary resources to meet the challenges. The purpose of this study was to determine the goals that families in which the mother had chronic illness identified for themselves and how these goals related to family functioning. A five-occasion, 15-month, descriptive longitudinal design was used to collect data. Data from occasions 2 and 3 were used to generate the coding scheme. This coding scheme was used to analyze the fourth-occasion data set, which is presented here. The sample at the fourth occasion consisted of 103 families in which the mother was diagnosed with breast cancer, diabetes, or fibrocystic breast disease. Content analysis of responses revealed 10 mutually exclusive categories of family goals: viability of children, cohesion, adaptation, boundary alterations, health maintenance, conflict management, individual achievements and pursuits, acquisition of possessions, financial stability, and family relocation. Types of goals identified did not significantly differ by disease type. The results suggest that family-system goals are relatively enduring and not readily discarded in response to health or illness disruption. PMID- 7870656 TI - The impact of home visits on enrollment patterns in pregnancy-related services among low-income women. AB - Medicaid now reimburses for care-coordination services for pregnant women in about half of the states. This care-coordination project targeted low-income pregnant women in two Indianapolis neighborhoods that historically have had high black-infant mortality rates. The service provided home visits by teams of workers including registered nurses, social workers, and indigenous community health workers. This retrospective descriptive study evaluated the impact of the home visits on enrollment in pregnancy-related services. Data were collected from the care-coordination records of 381 participants who delivered infants between July 1, 1990, and January 1, 1992. The proportion of participants enrolled in prenatal care, the Special Supplemental Food Program for Women, Infants and Children (WIC), Medicaid, and Food Stamps increased significantly following admission to care coordination. The majority of participants who enrolled in prenatal care and WIC, after admission to care coordination, did so within one month of admission. Home visits were effective in stimulating enrollment in pregnancy-related services. Further studies need to be done to evaluate the impact of home visits on pregnancy outcomes as well as their cost-effectiveness. PMID- 7870657 TI - An information manager for the Assessment Protocol for Excellence in Public Health. AB - The Assessment Protocol for Excellence in Public Health (APEXPH) is a method for comprehensive public health planning that can be implemented by state and local health departments. Many local health departments have limited resources for the data analysis and synthesis needed for APEXPH. To facilitate the implementation of APEXPH in Michigan, we used the Centers for Disease Control and Prevention (CDC) Epi Info software package to develop an APEXPH information manager (CDC AIM) for use by the 50 local health departments in that state. This report describes our methods for formatting, compressing, and presenting data. Examples of tables are provided for demographics by age and sex, numbers of deaths, years of potential life lost, crude mortality rates, and perinatal indicators such as low birthweight. Areas where additional work is needed to further improve CDC-AIM are discussed. Our experience in Michigan suggests that CDC-AIM potentially is an extremely helpful tool to assist state and local health departments in working with their communities to establish public health program plans based on mortality, morbidity, and risk-factor data. PMID- 7870658 TI - Case-management of AIDS clients as a predictor of total inpatient hospital days. AB - AIDS has shifted from an acute short-term terminal illness to a progressive, chronic disorder. Evaluation of AIDS case-management is imperative due to both the increasing numbers of cases and the lengthened survival of those with the disease. In 1988 the Missouri Department of Health (MDOH) initiated the first statewide system of AIDS case-management in the United States. This study was done to determine if deceased AIDS clients who received MDOH case-management services had fewer inpatient hospital days than clients who did not receive these services, during the last six months of life. Death certificates and Medicaid records were merged for 100 case-managed and 99 control, non-case-managed AIDS clients. No significant difference between groups was found in number of inpatient hospital days. Further, neither age, ethnicity, gender, cause of death, nor specific AIDS risk factors were associated with total number of inpatient hospital days. The client-centered philosophy of the program may have encouraged case managers to utilize all available service, including hospitalization, without considering cost-containment issues. Future evaluation efforts will investigate both cost-containment and quality-of-life indicators, such as satisfaction with care, of case-managed AIDS clients. PMID- 7870659 TI - Too many medications, too little money: how do patients cope? AB - Many individuals with chronic illnesses have multiple medications prescribed that often are not covered by third party payers. In South Carolina, Medicaid pays for only three prescriptions per month per recipient. A qualitative pilot study was conducted to learn how Medicaid recipients with more than three prescriptions decide which ones to have filled under Medicaid and what they do about the remaining medications. Nineteen Medicaid recipients who had more than three prescriptions were interviewed in their homes. Research participants paid for medications out-of-pocket, borrowed money, were extended credit by the pharmacy, got samples from the physician, did not get prescriptions filled or refilled, took medicines less frequently or in lower doses to stretch their supply, and very infrequently took someone else's medication. These individuals decided which medications to take based on: their perceptions of the importance of the medication or the seriousness of the condition for which it was prescribed, current symptoms, and the drug's cost. Some participants had to choose monthly whether to buy medications or food. PMID- 7870660 TI - School nursing in America--1902-1994: a return to public health nursing. AB - In October 1902, Lina Lavanche Rogers began her work in the New York City schools as the first school nurse in the United States. The purpose of this research was to examine the evolution of school nursing as it exemplifies development of a public health nursing specialty. Historiographic methodology was used. Primary sources included materials written by pioneers in school nursing. Secondary sources included journals, books, newspapers, biographical materials, and unpublished materials from the archives of health care and educational institutions and agencies. Public health nurses in 1902 had a model for practice that was considerably more independent and interdependent than that characterizing the practice of hospital nurses. From its origins in public health nursing, the role of the school nurse shrunk in many school systems to that of dispenser of bandages and aspirins, only to return once more to an advanced practice model. HIV, tuberculosis, sexually transmitted diseases, addiction, and violence have returned and/or replaced the contagious diseases of 1902 and the early years of school nursing. New immigrants, poverty, homelessness, and lack of primary care offer challenges to school nurses to meet the needs of schoolchildren and their families in the 1900s. PMID- 7870661 TI - Student experiential learning: a collaborative community practice project. AB - Theoretical and experiential learning in community assessment are essential components of the preparation of first-level community health nurses. This article describes a collaborative community practice project in which faculty incorporated senior baccalaureate community health nursing students as participants. Students assessed availability and utilization patterns of health care services in Spokane, Washington. Data derived from the survey were used by community planners in addressing issues of access to health care by low-income persons. Learning outcomes of this experiential process are described within the context of Burnard's Experiential Learning Model and community health nursing course objectives. Recommendations for design of similar experiential learning opportunities are made. PMID- 7870662 TI - Hepatic blood flow measurements and indocyanine green kinetics in a chronic dog model. AB - The objective of this study was to compare hepatic blood flow measurements using ultrasonic flow probes and ICG in a conscious dog model and to evaluate whether ICG can be used to estimate relative change in hepatic blood flow. Seven mongrel dogs (3 M, 4 F, BW = 21 +/- 1.8 kg, Hct = 0.39 +/- 0.05) were used in the study. Catheters were surgically inserted into carotid artery and portal, hepatic and jugular vein. Transit-time ultrasonic flow probes were implanted around the portal vein and hepatic artery. After two weeks of recovery, a single i.v. bolus dose of ICG (0.5 mg/kg) was administered to each dog. The disposition profiles for ICG in the four catheters were measured for 15 minutes and the hepatic blood flow reading from the probes recorded. Jugular vein ICG blood clearance (Cl = 5.9 +/- 1.1 ml/min/kg) was low compared to the electronically measured hepatic blood flow rate (Q = 27.8 +/- 9.1 ml/min/kg). Extraction ratios (E = 0.15 +/- 0.05) estimated using data from the inlet and the outlet of the liver were consistent with the clearance values, suggesting that ICG is not highly extracted by dog livers. Three dogs were used in experiments where liver blood flow was increased by food intake. Consistent with characteristics of low extraction ratio drugs, ICG was insensitive to blood flow changes while there was an overall increase in electronically measured liver blood flow of 30%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870663 TI - Carrier-mediated transport of H1-antagonist at the blood-brain barrier: a common transport system of H1-antagonists and lipophilic basic drugs. AB - The blood-brain barrier (BBB) transport system for H1-antagonists was studied using primary cultured bovine brain capillary endothelial cells (BCEC). The uptake of [3H]mepyramine was inhibited by various H1-antagonists. Ketotifen competitively inhibited [3H]mepyramine uptake with an inhibition constant (Ki) of 46.8 microM. Lipophilic basic drugs such as propranolol, lidocaine and imipramine significantly inhibited [3H]mepyramine uptake. In particular, propranolol inhibited [3H]mepyramine uptake competitively at an inhibition constant (Ki) of 51.1 microM. Moreover, in ATP-depleted BCEC, [3H]mepyramine uptake was stimulated by preloading with H1-antagonists and lipophilic basic drugs. These results indicated that H1-antagonists are transported across the BBB via a carrier mediated transport system common to lipophilic basic drugs. PMID- 7870664 TI - Effect of renal or hepatic dysfunction on neurotoxic convulsion induced by ranitidine in mice. AB - We investigated the effect of acute renal and hepatic dysfunction on the neurotoxicity of ranitidine, a histamine H2 receptor antagonist. Experimental acute hepatic and renal dysfunction in mice were produced by i.p. injection of uranyl nitrate (UN) and carbon tetrachloride (CT), respectively. Ranitidine was then constantly infused into the tail vein until the onset of clonic convulsion. When compared to control mice, UN treated mice had a significantly shorter onset time to clonic convulsion, lower total dose and higher plasma concentration at initiation of clonic convulsion. In contrast, the convulsive threshold concentration in the brain of UN treated mice was not significantly different from that of control mice. In CT treated mice, all pharmacokinetic and pharmacodynamic data described above were not significantly different from those of the control mice. No significant difference in the brain/plasma concentration ratio was observed between both disease models and the corresponding control mice. Finally, the effect of UN and CT treatment on the convulsive potency after intracerebral (i.c.) administration of ranitidine was investigated in mice. Potentiation of the intrinsic neurotoxic sensitivity to ranitidine could not be demonstrated for mice with renal or hepatic dysfunction. From these findings, we conclude that renal dysfunction is a risk factor for ranitidine neurotoxicity, and this increased risk results from increase in the drug concentration in plasma and brain as a result of impaired renal excretion. No apparent effect of acute hepatic dysfunction was observed on both the pharmacokinetic and pharmacodynamic behavior of the drug. PMID- 7870665 TI - First-pass effect of cis-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)- cyclohexyl) benzamide (U-54494) in rats--a model with multiple cannulas for investigation of gastrointestinal and hepatic metabolism. AB - A multiple cannulated rat model was utilized to investigate the relative contribution of the gut and liver as sites of first-pass metabolism of orally administered U-54494A, an anticonvulsant drug candidate. Each rat received a dose of U-54494A by oral, intraportal, and intravenous routes on three separate occasions. Intraportal and intravenous doses were administered through chronic cannulas surgically implanted in the portal vein and superior vena cava, respectively. Blood samples were collected over a 6-hr period from the superior vena cava cannula. The mean (n = 3) bioavailability of orally dosed U-54494A was 4.5 +/- 1.1%, while that dosed intraportally was 19.1 +/- 3.0%. The relative contribution of the gut and liver as sites of first-pass extraction and/or metabolism of orally administered drug was 69.9 +/- 14.0% and 24.5 +/- 12.2%, respectively. Approximately 35 to 40% of the total plasma clearance was attributeds to the liver. The plasma concentrations of the four known metabolites of U-54494A were apparently higher for the oral and intraportal routes compared to that after intravenous administration. This investigation confirms that the low oral bioavailability of U-54494A in the rat can be primarily attributed to both extensive intestinal and hepatic first-pass metabolism. PMID- 7870666 TI - Pharmacokinetics of intranasally-administered dihydroergotamine in the rat. AB - Intranasal dosing of dihydroergotamine (DHE) allows convenient self administration and provides an alternate route of administration for the treatment of migraine in addition to the existing parenteral dosage forms. In this study, the pharmacokinetics of 3H-DHE were investigated following intravenous and intranasal dosing (0.343 mg DHE/animal) in the rat. Intranasal administration of DHE resulted in rapid absorption. The extent of absorption of the radiolabeled dose was approximately 45%-60%. Absolute bioavailability of the parent drug was 35%-40%, as determined by deconvolution and by the ratios of AUC0 infinity following intranasal and intravenous dosing. Due to the limited capacity of the nostrils, approximately half of the intranasal dose was swallowed into the gastrointestinal tract. Biliary excretion was found to be the predominant pathway of radioactivity excretion following both routes of administration. The results from this study suggest that intranasal administration provides a viable means of delivering DHE into the systemic circulation. PMID- 7870667 TI - Identification of the diastereomers of pentobarbital N-glucosides excreted in human urine. AB - A study was undertaken to determine if humans excreted pentobarbital N-glucosides as urinary metabolites following oral administration of pentobarbital. (1'RS,5RS) 1-(beta-D-Glucopyranosyl)pentobarbital ((1'RS,5RS)-PTBG) was isolated from the urine of one subject. The two diastereomers, (1'RS,5R)-PTBG and (1'RS,5S)-PTBG were separated and found to be identical to synthetic standards when compared using HPLC retention times coupled with UV (with and without post-column ionization) and mass spectrometry (HPLC/MS). A HPLC method was developed for detecting and quantifying (1'RS,5R)-PTBG, (1'RS,5S)-PTBG and pentobarbital in urine. Following a single oral dose of sodium pentobarbital to male subjects (n = 6), 1.6-6.2% of the pentobarbital dose was excreted as (1'RS,5S)-PTBG over 60 hours. (1'RS,5R)-PTBG was also detected in one subject and accounted for 0.3% of the pentobarbital dose. Using a modified HPLC system, the four pentobarbital N glucosides were resolved and analysis of a partially purified pentobarbital N glucoside extract from one subject indicated that only (1'R,5R)-PTBG and (1'S,5S) PTBG could be detected as urinary excretion products. These results indicate that the side chain chirality of pentobarbital may influence the observed enantioselectivity for the formation and/or urinary excretion of the pentobarbital N-glucosides. PMID- 7870668 TI - The influence of net water absorption on the permeability of antipyrine and levodopa in the human jejunum. AB - Food ingestion can influence the absorption of levodopa in the intestine and thereby contribute to fluctuations of motor functions in Parkinson patients. Obstruction of the active transport of levodopa by amino acids can be one factor. Paracellular drug absorption, a route proposed to be influenced by net transport of water across the intestinal epithelium, might occur for a small and hydrophilic drug such as levodopa. In the present study we studied how luminal L leucine (60 mmol/L), alone or combined with hypotonicity, might stimulate net water absorption, and levodopa uptake in the human small intestine, since this possibly can contribute to the variable intestinal absorption of levodopa. The Loc-I-Gut perfusion technique was used in 10 healthy volunteers to study the effects of induced net fluid absorption on the small intestinal absorption of levodopa (2.5 mmol/L). An induced net fluid absorption was observed only when L leucine was combined with a hypoosmolar perfusion solution. However, this did not enhance the intestinal permeability of levodopa. In conclusion, we suggest that the variability in the absorption of levodopa in Parkinson's disease cannot be explained by differences in transmucosal water flux in the human small intestine. PMID- 7870669 TI - Quantitative analysis of a drug in an animal feed employing sample preparation by supercritical fluid extraction. AB - A pharmaceutical agent has been quantified in a rat feed matrix wherein sample preparation was achieved by supercritical fluid extraction. Spiking levels ranged from 0.0335% to 1.12%. Pure carbon dioxide, solid phase trapping on stainless steel with acetonitrile and liquid chromatographic assay yielded recoveries greater than 90% with relative standard deviations less than 5% in all cases except for the lowest spiking level. In this case recovery was 89.6% with an RSD of 9.6. PMID- 7870670 TI - Effects of configuration around the chiral carbon atoms on the crystal properties of ephedrinium and pseudoephedrinium salicylates. AB - The physicochemical properties and crystal structures of the crystalline salts formed by the interaction of an achiral anion, salicylate, with homochiral and racemic ephedrinium and pseudoephedrinium cations were determined. The interaction of ephedrinium or pseudoephedrinium with salicylate in aqueous solution yielded crystalline salts with the notable exception of homochiral ephedrinium. Evaporation of the solvent from solutions of homochiral ephedrine and salicyclic acid in various organic solvents, as well as grinding together solid homochiral ephedrine and solid salicylic acid, yielded viscous semisolids suggesting that homochiral ephedrinium salicylate has a low melting point and/or a high aqueous solubility. Mixing of the two viscous solids, obtained by grinding each of the opposite enantiomers of ephedrine with equimolar salicylic acid, resulted in the formation of racemic ephedrine and subsequently, upon heating, in the formation of racemic ephedrinium salicylate. While racemic ephedrinium salicylate exists as a crystalline compound (P2(1)/n space group) with an equal number of opposite enantiomers in the unit cell, its diastereomer, racemic pseudoephedrinium salicylate, exists as a conglomerate, i.e. a physical mixture, of the homochiral crystals of the opposite enantiomers (each P2(1) space group). The inability of homochiral ephedrinium to exist as a crystalline salicylate salt at 20-25 degrees C is attributed to its high energy conformation and/or to the poor packing of homochiral ephedrinium salicylate molecules in the crystal lattice. PMID- 7870671 TI - The measurement of mixture homogeneity and dissolution to predict the degree of drug agglomerate breakdown achieved through powder mixing. AB - Interactive mixing of agglomerates of small, cohesive particles with coarse carrier particles facilitate the deaggregation of agglomerates. In this study dispersion of agglomerates of microfine furosemide particles by such a mixing process was followed by measuring changes in the content uniformity and area under the dissolution curve. Interactive mixtures between agglomerates of different sized furosemide particles and coarse sodium chloride particles were prepared using different mixers, mixing times and mixer speeds. The dissolution rate of the drug from and content uniformity of the mixtures were measured, and degrees of dispersion were calculated. These degrees of dispersion were compared to the dispersion values obtained from the decrease in agglomerate size after mixing. An increase in mixing time led to an increase in dispersion. An initial fast deagglomeration, indicated by an increase in dissolution, increase in content uniformity and a decrease in particle size, was followed by substantially slower deaggregation of remaining agglomerates and smaller aggregates. For all mixtures studied the degree of dispersion estimated from dissolution measurements, when compared to equivalent content uniformity measurements, agreed closely with the degree of dispersion as indicated by the decrease in particle size. The use of the area under the dissolution curve to predict agglomerate breakdown proved useful and may find application in situations where it is impossible to follow directly deagglomeration through particle size measurements. PMID- 7870672 TI - Properties of free films prepared from aqueous polymers by a spraying technique. AB - A spray method for the preparation of free films from aqueous polymeric dispersions was investigated. Free films were prepared from aqueous dispersions of methacrylic acid-ethyl methacrylate copolymer (Eudragit L 30D), hydroxypropyl methylcellulose acetate succinate (HPMCAS), cellulose acetate phthalate (CAP), and ethyl cellulose (EC) by a spray method and a cast method, and their mechanical properties and reproducibility were investigated. Uniform films were obtained from the dispersions of Eudragit L 30D, HPMCAS, and EC by the spray method, but films could not be formed by spraying the CAP dispersion. The tensile strength, elongation, and elastic modulus of the sprayed Eudragit L 30D films were similar to the properties of the cast films, and good reproducibility was obtained from both methods. Marked within-run variation in the mechanical properties was observed for the cast HPMCAS and CAP films, which could be due to a settling of the solid particles during the drying step. The variation in the mechanical properties of the sprayed HPMCAS films was lower and the tensile strength significantly higher than that of the cast films. There were also significant differences in tensile strength and elongation of EC films between products of the two methods. The results indicated that the spray method used to prepare the free films from aqueous polymeric dispersions provided uniform films with consistent and reproducible properties. PMID- 7870673 TI - Development and characterization of microencapsulated microspheres. AB - A process for the coating of polymer microspheres with the same or different polymers and the characterization of these particles is described. Coated microspheres were manufactured from degradable and non-degradable polymers. Several physicochemical methods were used to establish that the particles were fully coated. Polarized light microscopy revealed strong birefringence of coated microspheres resulting in the appearance of Maltese Crosses on coated microspheres. After staining the core and the coating of particles using different fluorescent dyes, the uneven distribution of the dyes in the core and on the surface allows one to verify the coating success. After cutting microspheres using a cryomicrotome we were able to assess the microstructure of the coated microspheres. Electron Spectroscopy for Chemical Analysis (ESCA) was used to determine the surface composition of coated microspheres. Determining the carbon and oxygen content of samples we were able to verify the completeness of the coating procedure. To examine the benefit of coating microspheres, the effect of coating on the release of tetanus toxoid from polylactide microspheres was studied as a possible pharmaceutical application. PMID- 7870674 TI - Transepithelial transport and metabolism of thyrotropin-releasing hormone (TRH) in monolayers of a human intestinal cell line (Caco-2): evidence for an active transport component? AB - Cell culture models for gastrointestinal transport and metabolism are important mechanistic tools. Our studies of Caco-2 monolayers demonstrate heterogeneity in transport characteristics depending on passage number and origin of the cells. In accordance with data obtained in animals and humans, TRH shows a carrier mediated, saturable transport component, which operates parallel to a passive pathway in Caco-2 cells at passage number 89-99. At low TRH concentrations (< 3 mM) active transport becomes prominent, as demonstrated by the temperature dependence of TRH transport and inhibition experiments. The Michaelis-Menten parameters of the active, saturable transport component are: Km = 1.59 mM and Vmax = 1.84 microM/min. The pH optimum was determined to be at pH 6.0. On the other hand an exclusively paracellular passive route was found with Caco-2 cells at passage number 30-34. These results are also in agreement with observations made by others in cell culture experiments. The aspect of rigorously characterizing the specific Caco-2 clone under investigation is emphasized, especially when active transport mechanisms are suspected. PMID- 7870675 TI - Aggregation pathway of recombinant human keratinocyte growth factor and its stabilization. AB - Recombinant human keratinocyte growth factor (rhKGF) is prone to aggregation at elevated temperatures. Its aggregation pathway is proposed to proceed initially with a conformational change which perhaps results from repulsion between positively charged residues in clusters forming heparin binding sites. Unfolding of the protein leads to formation of large soluble aggregates. These soluble aggregates then form disulfide cross-linked precipitates. Finally these precipitates are converted to scrambled disulfides and/or non-disulfide cross linked precipitates. Stabilizers such as heparin, sulfated polysaccharides, anionic polymers and citrate can greatly decrease the rate of aggregation of rhKGF at elevated temperatures. These molecules may all act by reducing charge repulsion on the protein thus stabilizing the native conformation. EDTA, on the other hand, is found to inhibit disulfide formation in aggregates and has only a moderate stabilizing effect on rhKGF. PMID- 7870676 TI - In vitro cutaneous and percutaneous delivery and in vivo efficacy of tetracaine from liposomal and conventional vehicles. AB - The aim of this study was to quantitate drug delivery and correlate drug concentration in the skin with anesthetic effect. The rate of delivery of radiolabelled tetracaine from two different liposome formulas (1F2 and 23C2) and two conventional dosage forms (PEG Ointment USP and Glaxal base) was investigated in Flow-thru diffusion cells using human breast skin from mammoplasty. The results indicated a 1.5 and 4 times higher concentration of tetracaine within the skin when the liposomal formula (1F2) was used, compared to tetracaine in Glaxal base and PEG Ointment USP, respectively. The amount of drug delivered into the skin in 24 h from the liposomal formula was 5.3% of total applied whereas from Glaxal base it was 3.3% and from PEG Ointment base it was 1.2%. The amount of liposomal (1F2) phospholipids in the skin after 24h was 68.3 micrograms/cm2 (0.2% of total applied). The steady state flux of tetracaine from liposomes (1F2) was 16.06 micrograms/cm2/h with a lag time of 3.1h, from Glaxal base 10.24 micrograms/cm/h with a lag time of 11.2h and from PEG Ointment it was 5.70 micrograms/cm2/h with a lag time of 9.0h. The second liposome formula (23C2) showed similar flux and permeability coefficient than the Glaxal base, however the lag time was about half. The results indicated that optimized liposome formulation is necessary to achieve maximum drug delivery. The concentration of drug within the skin and the flux measured in vitro showed correlation with in vivo efficacy. The in vivo data showed that liposomal (1F2) tetracaine produced the deepest anesthesia with shortest onset in volunteers, followed by Glaxal base, liposome formula 23C2 while tetracaine in PEG Ointment had a lack of effect. PMID- 7870677 TI - Intestinal uptake of cimetidine and ranitidine in rats. AB - The H2-receptor antagonists exhibit unusual absorption behavior in that double peaks often occur after oral administration. Moreover, administration with some high potency antacids decreases the extent of absorption. To date, no explanation that can completely account for these observations has been advanced. One problem is that there is a lack of consensus as to the mechanism of absorption of the H2 receptor antagonists from the gastrointestinal tract. In the studies reported here, the mechanism and regional dependence of intestinal uptake of two H2 receptor antagonists, cimetidine and ranitidine, were investigated in rats using the in vitro everted ring technique. The uptake rate of cimetidine from both jejunum and colon was linear with concentration (in the range of 0.0005-40 mM), and there was no significant competition for uptake in the presence of the structurally similar H2-receptor antagonists, famotidine and ranitidine. In the case of ranitidine too, the uptake rate from the jejunum and colon was linear with concentration (in the range of 0.0005-5 mM), and there was no competition for uptake by either famotidine or cimetidine. These data indicate that uptake of cimetidine and ranitidine in the rat jejunum and colon occurs by a predominantly passive process. Both cimetidine and ranitidine exhibited regional differences in uptake rate. Uptake tended to be greatest in the ileum, similar in duodenum and jejunum, and lowest in the colon. However, differences in uptake rates between locations in the small intestine appeared to be too modest to account for the double peak behavior of either compound. PMID- 7870678 TI - A new bioerodible polymer insert for the controlled release of metronidazole. AB - This study evaluates a new class of bioerodible polymers as periodontal inserts for the controlled release of metronidazole. The system is based on association polymers formed from compatible blends of cellulose acetate phthalate (CAP) and a hydrophobic block copolymer of polyoxyethylene and polyoxypropylene, Pluronic L101. In addition to characterizing these polymers by thermal analysis, their erosion and metronidazole release characteristics were determined both in vitro, and in vivo using a rat model. The results show that increasing the concentration of Pluronic L101 in the blend to 50% and above leads to a sharp reduction in the rates of polymer erosion and metronidazole release. The characteristics of these slowly eroding films are potentially suitable for use as periodontal drug inserts with an effective duration of up to several days. Depending on the blend composition, the mechanism of metronidazole release was found to range from a surface erosion-controlled process to an erosion-modulated diffusion process. In all in vivo experiments, no signs of adverse tissue reactions were detected. Based on these results, prototype delivery inserts were designed and subsequently evaluated in volunteer patients. Preliminary results from this pilot study show that the metronidazole concentration in the gingival crevicular fluid was significant throughout the sampling period of up to 3 hr and remained well above the minimum inhibitory concentration for most periodontal pathogens. In addition, no discomfort or irritation was reported by the test subjects. PMID- 7870679 TI - Subzero thermal analysis of human stratum corneum. AB - The thermal behaviour of human stratum corneum was studied using differential thermal analysis within the temperature range of -130 degrees C to 120 degrees C. Aside from thermal transitions at around 40 degrees C, 70 degrees C, 85 degrees C and 100 degrees C, which have been reported before, a particular transition below 0 degree C (subzero), at approx. -9 degrees C (264 K), was noticed. This transition was present in the analysis curves of dehydrated as well as hydrated stratum corneum sheets and could be distinguished from the water peak found only in hydrated stratum corneum samples. To further characterize this transition, thermal analysis was performed on stratum corneum sheets: (i) after lipid extraction, (ii) after pretreatment of propylene glycol and (iii) after pretreatment of oleic acid/propylene glycol solution. From the results, it was concluded that the subzero transition (-9 degrees C) belongs to low melting lipid components of stratum corneum. PMID- 7870681 TI - Nasal absorption in the rat. III. Effect of lysophospholipids on insulin absorption and nasal histology. AB - The intranasal absorption enhancing and histological effects of a range of lysophospholipids has been investigated in the rat. Blood glucose levels fell rapidly following the administration of insulin (8 IU/kg) in combination with lysophosphatidylcholines (LPC; 0.625% w/v) which had ten or more carbon groups in their fatty acid chain. The effect of the LPC-caproyl (C6) was comparable to that of an unenhanced insulin formulation; the enhancing effect of LPC-decanoyl (C10) was similar to that of an LPC-palmitoyl/stearoyl (C16/C18) for similar concentrations. The effect of LPC-decanoyl was reduced with concentration but was still significant at 0.2% w/v (5mM). Lysophosphatidylglycerol (LPG) had a marked insulin absorption enhancing effect even at 0.0625% w/v. The histological effects of LPC-caproyl were similar to those of an unenhanced insulin formulation, while co-administration of LPC-decanoyl resulted in evidence of epithelial interaction. LPG (0.5% w/v) resulted in similar histological changes as LPC (0.625% w/v) (1), but at 0.0625% w/v no significant changes in epithelial integrity were observed. The length of the fatty acid residue of lysophospholipids was identified as an important factor for intranasal absorption enhancing activity. The nature of the polar head group may also have an influence. Increased insulin absorption was not necessarily accompanied by severe disruption of the nasal epithelium. Careful selection of lysophospholipid type and concentration may enable therapeutic drug levels to be achieved via the nasal route without prohibitive toxic effects. PMID- 7870680 TI - Effects of protease inhibitors on vasopressin transport across rat alveolar epithelial cell monolayers. AB - The transepithelial transport of arginine vasopressin (AVP) across cultured rat alveolar epithelial cell monolayers was studied. At 0.1 nM donor [125I]AVP, the radiolabel flux measured in the apical-to-basolateral (AB) direction was about 10 times greater than that in the reverse (BA) direction. HPLC analyses of the basolateral receiver fluid collected at the end of these flux measurements showed that about 97% of the total [125I]label represented subspecies of AVP, whereas the apical receiver fluid contained largely intact AVP (approximately 85% of total [125I]label). Both donor fluids contained virtually no degradation products of AVP (> 99%). In the presence of an excess 0.1 mM unlabeled AVP in the apical donor fluid, the Papp for radiolabeled AVP in the AB direction was decreased by approximately 68%, while the fraction of intact AVP in the basolateral receiver fluid was increased six-fold as compared to that observed at 0.1 nM [125I]AVP alone. Under this condition, the flux of intact AVP was approximately the same in both directions. When the concentration of apical camostat mesylate, an aminopeptidase inhibitor, was varied from 0 to 2 mM, the radiolabeled flux in the AB direction (with 0.1 nM [125I]AVP in the donor fluid) was significantly decreased in a dose-dependent manner, yielding commensurably elevated concentrations of intact AVP in the basolateral receiver fluid. In contrast, leupeptin (0.5 mM), a serine protease inhibitor, was without effect. These data, taken together, suggest that apically-presented AVP undergoes proteolysis (most likely by peptidases localized at apical cell membranes of alveolar epithelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870682 TI - Dermal microdialysis sampling in vivo. AB - Microdialysis sampling of the dermis in vivo was accomplished using a linear microdialysis probe. In contrast to previous studies using a commercial cannula style microdialysis probe, the linear probe had no effect on the flux of drug through the skin in vitro. The extent of tissue damage in vivo due to probe implantation was evaluated by histological examination and microdialysis delivery studies. Tissue damage due to implantation of the linear probe was minimal with no bleeding or edema observed. Infiltration of lymphocytes into the tissue was observed beginning 6 hours after probe implantation with scar tissue beginning to form after approximately 32 hours. The infiltration of lymphocytes had no effect on the behavior of implanted microdialysis probes. Delivery of 5-fluorouracil was between 20 and 25% for six different probes implanted in six different animals demonstrating good probe-to-probe and implantation-to-implantation reproducibility. Constant delivery was maintained for at least 24 hours in all cases indicating that experiments of at least 24 hour duration are feasible. The dermal concentration of topically applied 5-FU cream, Efudex, was continuously monitored by an implanted microdialysis probe demonstrating the feasibility of this technique as for monitoring skin drug levels in vivo. The dermal concentration of 5-FU following topical application was approximately 40-fold higher for in vitro excised skin than for in vivo intact skin. PMID- 7870683 TI - Colonic absorption and bioavailability of the pentapeptide metkephamid in the rat. AB - The concept of delivering systemically active peptide drugs to the colon in order to improve their oral absorption requires reasonable peptide permeability of the large intestinal wall and stability against the activity of the colonic microflora. In addition, the role of hepatic extraction needs to be addressed. In this study the absorption of the pentapeptide metkephamid following single pass perfusion of rat ascending colon was investigated by monitoring its disappearance from the large intestine and simultaneous appearance in the portal vein, the hepatic vein and the aorta. In addition its stability against colonic microflora was tested in vitro using pig caecal contents. Metkephamid was absorbed from the large intestine and appeared in the blood circulation; peptide concentrations in the portal vein increased over-proportionally with increasing perfusate concentrations (0.1-4.6 mmol/L) from 0.19 microgram/mL +/- 0.12 (SD, n = 7) to 31.6 micrograms/mL + 20.65 (SD, n = 4), respectively, and thus suggesting a saturable transport or metabolism. Concentrations in the hepatic vein were significantly lower than in the portal vein, hepatic extraction ratios were 0.35 +/- 0.14, 0.61 +/- 0.18 and 0.62 +/- 0.28 (SD, n = 4) for 0.1, 0.5 and 1.0 mM metkephamid perfusate concentrations, respectively. In the anaerobic colon metabolism model the degradation half-life of the peptide was 14.9 hours, thus, indicating relative stability in the bacterial environment of the colon. The results of the present study encourage further investigations on colonic delivery of peptide drugs. PMID- 7870684 TI - Kinetic analysis of the drug permeation process across the intestinal epithelium. AB - The rat intestinal lumen and the blood vessel were simultaneously perfused to study drug permeation across the intestinal epithelium. On the basis of drug disappearance from the intestinal lumen and its appearance into the vascular outflow, the mean time required for permeation across the intestinal membrane (MPT) and the permeation clearance (CLp) were calculated. MPT values of water, antipyrine, propranolol, imipramine and mannitol, varied from 0.45 min to 9.91 min depending on their physicochemical property. From both MPT and CLp, five drugs were classified as being (i) highly and rapidly absorbed (water, antipyrine), (ii) highly but slowly absorbed (propranolol, imipramine) and (iii) low and slowly absorbed (mannitol). Permeation profiles of these drugs were analyzed based on the diffusion model which defined the parameter for each permeation process, i.e. partitioning to and diffusion through the epithelium and clearance into the blood flow. Propranolol and imipramine partitioned into the membrane at a higher level than the other drugs. However, the clearance of both drugs from the epithelium was extremely slow, suggesting that this process is the rate-limiting step in their permeation. On the other hand, the rate-limiting step in the permeation of water and antipyrine was found to be the diffusion process in the epithelial layer. PMID- 7870685 TI - Antiinflammatory drug-induced small intestinal permeability: the rat is a suitable model. AB - Excretion of orally administrated 51Cr-EDTA as a marker of small intestinal permeability (a proposed prerequisite for human enteropathy) is increased by corticosteroids and non-steroidal antiinflammatory drugs (NSAIDs). We have investigated the suitability of the rat as an animal model of small intestinal permeability using orally administered 51Cr-EDTA. We dosed Sprague-Dawley rats with NSAIDs and corticosterone followed by 51Cr-EDTA under conditions reported for humans and measured urinary excretion of the marker. In control rats, the urinary excretion of 51Cr-EDTA exhibited a skewed-to-the-left frequency distribution curve with a median of 2.13% of the dose. No sex-related differences were noticed in the baseline permeability. In male rats, single therapeutically equivalent doses of indomethacin, flurbiprofen, ibuprofen, naproxen, diclofenac, sulindac, nambumetone, and corticosterone, increased the intestinal permeability by different extents with indomethacin eliciting the maximum effect, and the last four drugs showing minimal potencies. Therapeutically relevant doses of aspirin did not have any significant effect. The increase in permeability was dependent upon the NSAIDs dose. Administration of glucose/citrate, misoprostol and sulfasalazine significantly reduced the effect of indomethacin. Misoprostol antagonized the effect of naproxen but H2-antagonists and sucralfate did not. All the above observations made in the rat were similar to those previously reported for humans. Thus the rat is a suitable model for studies of small intestinal permeability. PMID- 7870686 TI - Transdermal delivery of metoprolol by electroporation. AB - Electroporation, i.e., the creation of transient "pores" in lipid membranes leading to increased permeability, could be used to promote transdermal drug delivery. We have evaluated metoprolol permeation through full thickness hairless rat skin in vitro following electroporation with an exponentially decaying pulse. Application of electric pulses increased metoprolol permeation as compared to diffusion through untreated skin. Raising the number of twin pulses (300 V, 3 ms; followed after 1 s by 100 V, 620 ms) from 1 to 20 increased drug transport. Single pulse (100 V, 620 ms) was as effective as twin pulse application (2200 V, 1100 V or 300 V, 3 ms; followed after 1 s by 100 V, 620 ms). In order to investigate the effect of pulse voltage on metoprolol permeation, 5 single pulses (each separated by 1 min) were applied at varying voltages from 24 to 450 V (pulse time 620 ms). A linear correlation between pulse voltage and cumulative metoprolol transported after 4 h suggested that voltage controls the quantity of drug delivered. Then, the effect of pulse time on metoprolol permeation was studied by varying pulse duration of 5 single 100 V pulses from 80 to 710 ms (each pulse also separated by 1 min). Cumulative metoprolol transported after 4 h increased linearly with the pulse time. Therefore, pulse time was also a control factor of the quantity of drug delivered but to a lesser extent than the voltage at least at 100 V.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870687 TI - In vitro and in vivo evaluation in dogs and pigs of a hydrophilic matrix containing propylthiouracil. AB - A hydrophilic matrix tablet containing 300 mg of propylthiouracil was formulated with several types of hydroxypropylmethylcellulose. The influence of polymer and drug granule particle size, polymer concentration, crystallinity and geometry of the polymer particles, the polymer incorporation outside or inside the granule, addition of a filler and tablet hardness were studied. Polymer concentration, polymer particle size and geometry, filler addition and type of the filler used had a major influence on in vitro drug dissolution profiles. The bioavailability of propylthiouracil in dogs from the hydrophilic matrices investigated was low, because of the short gastro-intestinal transit times of the matrix tablets in the dogs. The matrix tablets reached the colon in fasted dogs within 2-3 hours after administration. The results indicated the poor predictability of bioavailability experiments in dogs with hydrophilic matrices. Although the bioavailability data in pigs seemed promising, a transit time study revealed a long stomach residence time of the matrix tablets in pigs. These data suggested that pigs are an inappropriate animal model for bioavailability studies of erodible matrix tablets. PMID- 7870688 TI - Pharmacokinetics of two enteric-coated ketoprofen products in humans with or without coadministration of omeprazole and comparison with dissolution findings. PMID- 7870689 TI - In vitro plasma metabolism of RMP-7. PMID- 7870690 TI - Entrapping efficiency of an oil-in-water emulsion containing isocarbacyclin methyl ester (TEI-9090) in dog and human sera. PMID- 7870691 TI - Estimates of prescription rates and the use of medicaments for suicide. PMID- 7870692 TI - Nickel absorption from perfused rat jejunal and ileal segments. AB - The intestinal absorption of Ni2+ was studied in isolated perfused jejunal and ileal segments of rats, by a method which allows continuous sampling of the absorbates. The results showed that the Ni(2+)-absorption proceeds at a much higher rate in the jejunum than in the ileum. Several observations indicate that Ni2+ is absorbed actively in the jejunum. There are indications in the literature that Ni2+ at least partly may share the transport mechanism for iron across the intestinal mucosa and our results may reflect the participation of Ni2+ in this absorptive process. The transfer of Ni2+ across the ileal epithelium may occur by passive diffusion. Addition of Zn2+, Co2+, Cd2+ or Hg2+ to the jejunal perfusates affected the Ni(2+)-absorption to varying extents. Thus, Zn2+ had minor effects on the Ni(2+)-absorption. Co2+ decreased the Ni(2+)-concentration in the absorbates, possibly by interfering with Ni2+ in the iron transfer process. Addition of Cd2+ or Hg2+ to the perfusates resulted in decreased jejunal water absorption. Hg2+ also depressed the glucose absorption. These results show that Cd2+ and Hg2+ at low concentrations are toxic to the jejunal mucosal cells. Thus, these metals can inhibit the amount of Ni2+ transferred across the intestinal mucosa by decreasing the volume of the absorbate. PMID- 7870693 TI - Enhanced intestinal nickel absorption in iron-deficient rats. AB - The absorption of nickel was studied in isolated perfused jejunal and ileal segments of iron-deficient and iron-sufficient rats. The uptake of nickel in tissues of iron-deficient and iron-sufficient rats given a low oral nickel-dose was also examined. The results showed enhanced nickel absorption in vitro and in vivo in iron-deficient rats. In the in vitro perfusions, increased absorption was observed both in jejunum and ileum. The enhancement was very prominent in jejunum and the nickel concentration in the jejunal absorbate of iron-deficient rats even exceeded the nickel concentration in the perfusate. This indicates that nickel is absorbed actively in the jejunum of iron-deficient animals. Twenty-four hr after an oral dose of nickel the uptake of the metal in various tissues was 1.5-2.5 times higher in iron-deficient rats compared to iron-sufficient rats. Our data indicate that nickel is absorbed at least in part by the active transfer system for iron in intestinal mucosal cells. PMID- 7870694 TI - The pyrimido-pyrimidine derivatives, dipyridamole and RA-642, reduce opacification of crystalline lens in diabetic rats. AB - We assessed the effect of dipyridamole, RA-642 and mopidamol, on lenticular opacities in a model of experimental diabetic cataracts in rats. All three pyrimido-pyrimidine derivatives caused a statistically significant reduction of opacification in crystalline lens as compared with untreated diabetic animals. The production of superoxide anions (phenazine methosulphate [PMS]-induced nitroblue tetrazolium [NBT] reduction) showed a decrease of 81.6%, 78.9% and 1.8% in lens tissue homogenates from rats treated with dipyridamole, RA-642 and mopidamol, respectively. Dipyridamole and RA-642 produced a statistically significant inhibition (50% and 64.8%, respectively) of lipid peroxidation (ferrous sulphate and ascorbic acid [FeAs]-induced malondialdehyde [MDA] production) as compared with the group of untreated diabetic rats. Mopidamol did not exert any inhibitory effect on lipid peroxidation. There was a statistically significant correlation between opacification of lens and PMS-induced NBT reduction and FeAs-induced MDA production. We conclude that the protective effect of dipyridamole and RA-642 from free radical damage to crystalline lens in the model of experimental diabetes used in this study, is the result of the antioxidant action of these compounds. The effect exerted by mopidamol, however, suggest a possible complementary effect of the pyrimido-pyrimidine derivatives through interaction with other mechanisms (e.g., the sorbitol pathway) implicated in the development of cataracts. PMID- 7870695 TI - Effect of levomepromazine and metabolites on debrisoquine hydroxylation in the rat. AB - The influence of the major metabolites of the phenothiazine derivative, levomepromazine (methotrimeprazine), on hydroxylation of debrisoquine was examined in male Sprague-Dawley rats. The metabolic ratio of debrisoquine/4 hydroxy debrisoquine was first determined in rats after oral administration of 10 mg/kg of debrisoquine. Then the same dose of debrisoquine was co-administered with various doses of levomepromazine or one of its metabolites. Levomepromazine and its sulphoxidated, N-demethylated and O-demethylated metabolites caused highly significant and dose-dependent increases in the debrisoquine metabolic ratio. 3-Hydroxy levomepromazine had no significant effect on the metabolism of debrisoquine. This indicates that the non-hydroxylated metabolites of levomepromazine have relatively high affinities for the cytochrome P450 enzyme which converts debrisoquine to 4-hydroxy debrisoquine in the rat. Such metabolites may therefore be responsible for a considerable part of the inhibitory effect of debrisoquine hydroxylation previously reported in patients treated with phenothiazine neuroleptics. PMID- 7870696 TI - Methyl mercury during late gestation affects temporarily the development of cortical muscarinic receptors in rat offspring. AB - Pregnant Sprague-Dawley rats were treated by gavage with a single dose of 8 mg/kg of methyl mercury on gestational day 15. Offspring of control and treated rats were killed at 14, 21 and 60 days of age. The binding characteristics of muscarinic receptors labelled in cortical membrane preparation by 3H-L quinuclidinyl benzilate were studied together with the assessment of mercury level in the same brain area. Furthermore, the performance in passive avoidance tasks was evaluated in 8 weeks old rats. Perinatal exposure to methyl mercury significantly reduced the maximum number of muscarinic receptors (Bmax) in the brain of 14 (53%) and 21 day old rats (21%), while this change was no more present in 60 day old rats. This phenomenon seems to be strictly related to the presence of mercury in the cortex since it disappeared with the normalization of mercury levels in the brain. Despite the recovery of muscarinic receptor densities in methyl mercury exposed rats at 8 weeks of age, the avoidance latency was reduced in passive avoidance test as an indication of learning and memory deficits in these animals. Results from this study indicate that prenatal methyl mercury exposure induces latent cognitive dysfunction which does not seem to be related to transient muscarinic receptor alteration found in the early period of postnatal life. PMID- 7870697 TI - Toxicity studies on one-year treatment of non-diabetic and streptozotocin diabetic rats with vanadyl sulphate. AB - Streptozotocin-diabetic and non-diabetic rats were given vanadyl sulphate in drinking water at concentrations of 0.5-1.5 mg/ml for one year. It was found that vanadyl treatment did not produce persistent changes in plasma aspartate aminotransferase, alanine aminotransferase, and urea, specific morphological abnormalities in the brain, thymus, heart, lung, liver, spleen, pancreas, kidney, adrenal, or testis, or abnormal organ weight/body weight ratio for these organs in either non-diabetic or diabetic animals. Treatment significantly reduced the incidence of the occurrence of urinary stones in non-diabetic rats. In diabetic animals vanadyl treatment significantly reduced the mortality rate and prevented the elevation of plasma levels of alanine aminotransferase and urea, the increases in organ size, and the occurrence of megacolon but did not affect the development of renal and testicular tumours. Plasma and tissue concentrations of vanadium were determined and found to have the following order of distribution: bone > kidney > testis > liver > pancreas > plasma > brain. Vanadium was retained in these organs at 16 weeks following vanadyl withdrawal while the plasma levels were beneath detection limits. It is concluded that vanadyl sulphate at antidiabetic doses is not significantly toxic to rats following a one-year administration in drinking water, but vanadium may be retained in various organs for months after cessation of treatment. PMID- 7870698 TI - Excitatory actions of dehydroabietic acid on mammalian synaptosomes. AB - The presynaptic effects of dehydroabietic acid were investigated using mouse brain synaptosomes as the in vitro model. At concentrations ranging from 10 to 100 microM, dehydroabietic acid depolarises the synaptosomal membrane and causes pronounced release of the neurotransmitters gamma-aminobutyric acid, acetylcholine and L-glutamate. The effects on membrane potential and transmitter release occur predominantly at concentrations below which any lytic actions of this compound can be detected. Dehydroabietic acid-induced depolarisation and release of neurotransmitters are not influenced by tetrodotoxin and are associated with only marginal inhibition of membrane-associated ATPase activity. When synaptosomes are challenged with dehydroabietic acid in calcium-free saline, a partial reduction in the stimulated release of transmitters is observed. These results provide clear evidence that dehydroabietic acid is neuroactive and capable of causing substantial increases in the release of both excitatory and inhibitory neurotransmitter substances. The mechanism which underlies the neuroexcitatory effects of dehydroabietic acid remains to be resolved however it is proposed that release of transmitters from central nerve endings may be a contributory factor in the toxicity of resin acids. PMID- 7870699 TI - Protection by albumin against ischaemia- and hypoxia-induced hepatic injury. AB - In previous studies using isolated perfused rat livers, we have shown that reactive oxygen species are involved in hypoxic and ischaemic liver damage. Since albumin was shown to possess strong antioxidant properties we now investigated the capacity of albumin to prevent ischaemic and hypoxic damage in isolated perfused rat livers. Both, partial ischaemia and hypoxia/reoxygenation, resulted in marked hepatic injury as evidenced by an increased release of hepatic enzymes (GPT, LDH), by a strong decline of bile flow and by a decrease in hepatic GSH levels. With partial ischaemia, hepatic ATP depletion and calcium accumulation were also observed. Bovine serum albumin, added to the perfusate at concentrations of 0.1 or 1%, provided nearly complete protection against both types of liver injury. The same level of protection was also afforded by sulfhydryl-blocked and fatty acid-free bovine albumin preparations and by human albumin. In conclusion, the protective effect of albumin in our models of oxidative liver injury is neither due to the thiol moiety nor to the presence of oxidizable fatty acids in the albumin fraction. More likely, albumin provides protection by an unspecific binding of redox-active transition metal ions capable of catalyzing reactions which yield hydroxyl or hydroxyl-like radicals. Besides, unspecific sacrifice reactions of albumin with highly reactive oxygen species or other endogenous compounds may also be implicated. PMID- 7870700 TI - Effect of tetraethylthiuramdisulphide and diethyl-dithiocarbamate on nickel toxicokinetics in mice. AB - A new experimental pharmacokinetic model using the gamma-emitting isotope 57Ni for studying nickel toxicokinetics was employed in a recent investigation (Nielsen et al. 1993) in order to quantitatively study, for the first time, the effect of tetraethylthiuram disulphide (disulfiram, Antabuse, TTD) and sodium diethyldithiocarbamate (DDC) on whole-body retention and organ distribution of nickel in mice. TTD or its decomposition product DDC given orally by stomach tube shortly after oral administration of a low dose of nickel chloride labelled with 57Ni resulted in an approximately ten times higher whole-body retention of nickel compared to the retention in a control group exposed to nickel only. These chelators increased the whole-body retention of nickel also when given by intraperitoneal injection shortly after oral or intraperitoneal administration of nickel. Oral administration of a single dose of TTD or DDC rapidly after an oral dose of nickel chloride also resulted in extensive changes in the organ distribution of nickel, thus the nickel content in the brain was at least 700 times higher than in a control group given the same dose of nickel only. If DDC was given intraperitoneally after nickel given orally, the relative organ distribution of nickel to most organs was the same as if the chelator was given orally, though the contents of the liver and lungs were lower. That TTD and DDC resulted in a transport of nickel to the brain, is underlined by the fact that after 20 hr, approximately 15% and after 45-50 hr, 30% of the total body burden of Ni was found in the brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870701 TI - Increased intracellular potassium and water contents in rat heart after alpha-1 adrenoceptor stimulation. AB - Potassium accumulation in rat heart after alpha-1-adrenoceptor stimulation has previously been reported from indirect measurements. Here we present data on intracellular potassium content measured directly in the heart. Isolated rat hearts perfused in a non-recirculating system were exposed to alpha-1 adrenoceptor stimulation (5 x 10(-5) mol/l phenylephrine in the presence of 10( 6) mol/l timolol). 14C-Sucrose was used to estimate the extracellular space. From heart homogenates intracellular potassium, magnesium and cellular water contents were determined and the ion concentrations calculated accordingly. The intracellular magnesium content remained unchanged during all experimental conditions. alpha-1-Adrenoceptor stimulation evoked an increase in potassium content by 9% (4, 14; 95% confidence interval (CI), P = 0.0006). Due to an observed increase in intracellular water by 17% (9, 26; 95% CI, P = 0.0006), the potassium concentration apparently decreased by 8% (0.3, 15; 95% CI, P = 0.04). During partial inhibition of the Na+/K(+)-ATPase by 10(-5) mol/l ouabain, there was an increase in potassium content by 5% (1, 9; 95% CI, P = 0.008). There was, however, no significant increase in intracellular water in this situation. Calculated intracellular potassium concentration showed accordingly a slight increase. The effects upon potassium and water both in the absence and presence of ouabain were eliminated by the alpha-1-adrenoceptor blocker prazosin (10(-6) mol/l). alpha-1-Adrenoceptor stimulation apparently increased cellular dry weight by 10% (2, 18; 95% CI, P = 0.02). Changes in translocation of potassium and water must be considered as part of the alpha-1-adrenergic heart effects. PMID- 7870702 TI - Effect of atropine, HLo 7 and HI 6 on respiratory and circulatory function in guinea-pigs poisoned by O-ethyl S-[2-(diisopropylamino) ethyl] methylphosponothioate (VX). AB - In a guinea-pig model with on-line respiratory and circulatory monitoring the therapeutic efficacy of atropine, HLo 7 and HI 6 in VX poisoning was compared. In female urethane-anaesthetized Pirbright-white guinea-pigs the a. carotis, v. jugularis and trachea were cannulated. After base line measurements the animals received VX (22.5, 45 or 90 micrograms/kg = 5, 10 or 20 x LD50) intravenously and 2 min. later the antidotes: HLo 7 or HI 6 (30 mumol/kg, each) or atropine 10 mg/kg or a combination of atropine and one of the oximes (all intravenously). Respiratory and circulatory parameters were recorded for 60 min. or until death of the animal. Erythrocyte, brain and diaphragm acetylcholinesterase (AChE) activity was determined after the experiment. VX poisoning caused a rapid respiratory arrest within 4-5 min. Atropine treatment was effective in improving the respiratory function after VX, 22.5 micrograms/kg, but had only a small effect after the higher VX doses. The treatment of VX (10 or 20 x LD50) poisoned animals with oxime plus atropine improved respiration to various extents, restored circulation and prolonged the survival time, HLo 7 being more effective than HI 6 after VX 90 micrograms/kg. Oximes alone were completely ineffective. Erythrocyte and diaphragm AChE was reactivated by HLo 7 and, less effectively, by HI 6, while brain AChE remained almost completely inhibited in all groups. The results of this investigation demonstrate a reasonable efficacy of atropine after lower VX doses and of HLo 7 and HI 6 (plus atropine) after high-dose VX poisoning, HLo 7 being slightly more effective than HI 6. PMID- 7870703 TI - Derivatives of 2-nitrofluorene cause changes of human sperm motility. AB - The effects on human sperm motility characteristics of 2-nitrofluorene and selected derivatives were studied in vitro, using computer aided sperm analysis (Cellsoft). Substances to be tested were dissolved in acetone and added to separated spermatozoa in culture media to final concentrations of 100 and 1000 microM. Aliquots were removed immediately (< 5 min.) and 24 hr after the addition and tested for sperm motility characteristics. Four of the substances tested; 2,4,7-trinitrofluoren-9-one (2,4,7-tNFO), 2,5-diaminofluorene (2,5-dAF), 7 hydroxy-2-nitrofluorene (7-OH-NF) and 2,7-diaminofluorene (2,7-dAF) showed strong detrimental effects on the sperm motility. Slight detrimental effects were also recorded using 2-nitrofluorene and 2,5-dinitrofluorene (2,5-dNF). Weak stimulatory effects were obtained using 2-acetoamidofluorene (AAF) and 2,7 dinitrofluorene (2,7-dNF). No significant effects were seen with 5-hydroxy-2 nitrofluorene (5-OH-NF), 2-aminofluorene (AF), 2-aminofluoren-9-one (AFO), 2 amino-9-hydroxyfluorene (9-OH-AF) or 9-hydroxy-2-nitrofluorene (9-OH-NF). The mechanism behind this effect is not known but it could be speculated that these lipophilic substances interact with the membranes or the cellular respiration. PMID- 7870704 TI - Liver enzyme activities after multiple administration of nifedipine in mice. AB - The effect of multiple nifedipine administration on hexobarbital sleeping time, liver monooxygenase and synthetase activities, lipid peroxidation and microsomal membrane fluidity were studied in male albino mice. The drug was administered orally at a dose of 25 mg/kg daily for 14 and 21 days. Nifedipine caused enzyme induction, demonstrated by shortened hexobarbital sleeping time, enhanced ethylmorphine N-demethylase, aniline 4-hydroxylase, ethoxycoumarine O-deethylase, UDP-glucuronyl transferase, glutathione S-transferase and NADPH-cytochrome c reductase activities and increased content of cytochrome P450 and cytochrome b5. This effect persisted until the 7th day after the last dose of nifedipine. There were no changes in lipid peroxidation and fluidity of the microsomal membranes after 14-day nifedipine administration. The increased cytochrome P450 content and drug metabolizing enzyme activities could be not associated with changes in these liver microsomal membrane properties. PMID- 7870705 TI - Prolonged release from the injection site of morphine from morphine esters in an oil vehicle given by intramuscular injection to pigs. PMID- 7870706 TI - Effects of undernutrition during suckling and early post-weaning on the inhibition by met-enkephalin of striatal adenylate cyclase activity in adult rats. PMID- 7870707 TI - The area under the plasma concentration curve (AUC) of urethane in mice and the influence of concomitant administration of ethanol. PMID- 7870709 TI - [Role confusion in the post-divorce period]. AB - After some fundamental conceptional thoughts about working with families affected by separation and divorce and an excursion into the sociology of divorce the fate of children from divorced families is at the center of attention in the casuistic part of the article. The author describes the intra-psychic consequences of contradicting tole expectations and loyalty attachments which especially boys are subjected to when they are seriously drawn into their parents' conflicts. PMID- 7870708 TI - [The Freiburg Group Intervention Program for children of separated and divorced families]. AB - Group sessions for children from separated and divorced families are currently experiencing a boom with those responsible for private and public youth relief organizations. The aim of these sessions is to normalize separation and divorce for children, to encourage solidarity amongst them and to teach them strategies to cope with their situation early on. The authors present a group intervention program which consists of 17 group meetings, 2 evenings with parents and a prediagnostic session. Based on American curricula, it has been specially developed for educational counseling centers. Experiences regarding indication, implementation, choice of material and work with parents are presented and discussed. PMID- 7870710 TI - [Psychological expert assessment as an intervention in child custody conflicts during divorce]. AB - How to deal appropriately with families affected by divorce has also been discussed among psychological experts for years. In this article the psychological expert opinion in a divorce is described as a possibility of intervention in a current separation conflict. Based upon a process oriented and systemic point of view the corresponding main principles and approaches are described which are essential for the task of forming an expert opinion in such a conflict. PMID- 7870711 TI - [The ethical status of the child in family therapy and systemic therapy--response to criticism]. AB - A paper about the ethical status of the child in family therapy and child therapy published by the authors in this journal gave rise to criticism. To respond to the critics six systemic therapist were asked to comment on the paper. The results are presented. The paper is concluded by ideas of the authors concerning the future of the ethical discourse in psychotherapy. PMID- 7870712 TI - [Centralized control of the quality of diagnosis and detection of tuberculosis without pulmonary destruction and bacterial discharge]. AB - The City Supervision Committee (CSC) has been set up in St. Petersburg to control detection, quality of diagnosis and treatment of new-onset cases of tuberculosis without destruction and bacterial discharge. The CSC members contributed to unification of diagnostic and activity status techniques, helped introduce retrospective survey of fluorograms, raise responsibility of practitioners. The CSC activity was found beneficial for antituberculosis institutions of a large city. PMID- 7870713 TI - [Computer technology in the organizational-methodical management of tuberculosis services]. PMID- 7870714 TI - [Effects of different factors on work capacity status of patients with newly diagnosed pulmonary tuberculosis]. AB - As shown by medical disability expert commission which followed up 142 tuberculous patients throughout chemotherapy, the disability in new-onset tuberculosis cases is related both to medical and social factors. The jobs of 1/2 of the examinees were not fit for such patients. More than half of them had concomitant visceral lesions. The duration of temporary disability was consequent to many factors, the principal of which were dissemination and destruction: subjects with local infection without destruction were incapable 192 days, on the average, while those with tuberculosis dissemination and destruction 266 days. 14.1% became invalids. Only a small group of the patients were not in need of social support. PMID- 7870715 TI - [Role of immunologic studies in the diagnosis of tuberculosis in adolescents]. AB - Tuberculous antigens and antibodies, antigens and antibodies to pneumococcus, haemophilus bacteria. Klebsiella pneumonia, proteus bacteria were determined in 100 adolescents (87 with tuberculosis and 13 with nonspecific lung diseases). Specific antigens and antibodies were detected in 62% of tuberculous and 7.7% of nontuberculous patients. The most pronounced immune response to M. tuberculosis antigens and antibodies as well as to nonspecific flora was registered in patients with long-term and disseminated processes. Immunological investigations are thought an important tool in diagnosis, differential diagnosis of tuberculosis and planning combined treatment policy. PMID- 7870716 TI - [Characteristics of tuberculosis epidemiology in Moscow and improvement measures]. AB - The trends in tuberculosis morbidity for the recent 30 years and factors that caused tuberculosis incidence to rise by 13.5% in 1992 are analyzed. Infiltrative disseminated, disseminated and fibrous-cavernous tuberculosis were diagnosed in 58.7%, 11.7% and 1.8% of cases, respectively. Destructive lesion was found in 50% of the patients. Tuberculosis mortality reached in 1992 4.6 per 100,000. Measures to control tuberculosis spread in Moscow are suggested. PMID- 7870718 TI - [Effects of laser therapy on immunity in patients with bronchial asthma and pulmonary tuberculosis]. AB - In bronchial asthma alone and combined with active pulmonary tuberculosis there are marked shifts in immune system (diminished mature T-cell and suppressor subpopulation of T-lymphocytes) resulting in disordered immunoregulatory subpopulation relationships. Also, B-system immunity responded with hyperfunctional activity (increased count of B-lymphocytes and polyclonal gammaglobulinemia). As conventional methods fail to normalize the shifts, an adjuvant laser immunocorrection was tried. Laser radiation displayed a good immunocorrecting action and therefore is recommended for patients with bronchial asthma and associated diseases. PMID- 7870717 TI - [Immunological bases of tuberculin therapy in combined treatment of patients with pulmonary tuberculosis]. AB - Mantoux test with 2 TU and tuberculin test results gave evidence for the pattern of body responses. A form of tuberculin therapy is suggested. The latter is shown to stimulate a spontaneous and BCG-enhanced NBT test (p < 0.05) and specific desensitization in the absence of humoral immunity changes (IgM, IgG, IgA and titers of circulating antituberculous antibodies). PMID- 7870719 TI - [Effects of tobacco smoking on the course of infiltrative pulmonary tuberculosis and effectiveness of its treatment]. AB - Case records analyzed for 297 smokers and 141 nonsmokers with new-onset infiltrative pulmonary tuberculosis revealed strong relationships between smoking and the disease course, relevant treatment results. In smokers the disease took more severe and disseminated pattern with pulmonary tissue destruction and bacterial discharge. Involution of the specific process in smokers advanced slowly and prolonged hospital stay to 1.2 month. Discontinuation of bacterial discharge took place in 90.1% of smoking patients and in 100% of nonsmokers, the destruction caverns got closed in 58.2% and 76.4%, respectively. Educational antismoking activity and smoking treatment promotion in smoking patients with pulmonary tuberculosis are needed. PMID- 7870720 TI - [Significance of cyclic nucleotides in pathogenesis of cor pulmonale in tuberculosis of respiratory organs and the use of beta adrenoblockers]. AB - Blood levels of cyclic nucleotides and their actions on central hemodynamics were studied in 129 patients with pulmonary tuberculosis. A direct correlation was established between heart rate, pulmonary artery systolic pressure and concentrations of cyclic adenosine monophosphate. Basing on this finding, the authors propose introduction of beta-adrenoblockers in hyperkinetic circulation tuberculous patients to prevent cor pulmonale. Administration of anapriline in tuberculous patients with compensated cor pulmonale and symptoms of sympathoadrenal hyperfunction improves the patients' condition, promotes a decrease in cardiac output, cardiac index, systolic pressure in the pulmonary artery. No side effects of the drug were reported. PMID- 7870721 TI - [Surgical tactics in bilateral destructive pulmonary tuberculosis]. AB - 43 patients with pulmonary tuberculosis (mean age 36.8 years) were treated surgically. All the patients had disseminated bilateral disease with destruction. Preoperative bacteriological examination identified M.tuberculosis in 67.5% of the examinees. In two-thirds of them x-ray evidenced total pulmonary lesion. 40 subjects of all surgical patients underwent operation for bilateral fibrous cavernous tuberculosis with caverns location in the upper lobe or upper lobe and 6 segment. The disease was diagnosed to be 1-3 years in duration. The interventions developed in the Novosibirsk Research Institute of Tuberculosis included: osteoplastic thoracoplasty, resection following osteoplastic thoracoplasty, atypical extrapleural resection with limited thoracoplasty, open treatment of the caverns. The surgery resulted in marked improvement (abacillation, cavernous healing) in 42 patients. Long-term follow-up recorded cure in 41 patients (95.3%). PMID- 7870722 TI - [Use of biocompatible polymer implants in combination with extrafocal device fixation in the surgical treatment of spondylitis]. AB - The author summarized the data on experimental application of biocompatible implants IIIIIM-1 covered with benemycin as a treatment modality in spondylitis. The polymer implanted into the disease focus is able to maintain high concentration of the drug for 60 days. The implants were inserted in 120 tuberculous and 27 nonspecific spondylitis patients. Surgical intervention performed in 147 patients comprising radical resection of the destruction focus and vertebral defect replacement with biocompatible implant in combination with extrafocal apparatus fixation decreased the operation trauma++, secured stability of the anterior and posterior parts of the operated spine and allowed early active rehabilitation of postoperative patients, 2-3 months after the surgery the author observed good spinal stabilization and definite signs of clavus formation in the resection zone. PMID- 7870723 TI - [Association of generalized sarcoidosis and diffuse toxic goiter]. AB - The paper reports 2 cases of thyroid sarcoidosis associated with diffuse toxic goiter. This association is of a special interest because of suggested common mechanisms underlying etiopathogenesis of these two diseases attributed to immune disorders. Thyroid surgery and subsequent morphological examination in sarcoidosis patients require a purposeful search for epithelioid-cell granules in the thyroid tissue for diagnosis of thyroid sarcoidosis. PMID- 7870724 TI - [Radionuclide diagnosis of the ureteral motor function and urodynamics in renal tuberculosis and other diseases of the urinary system]. AB - Radionuclide methods (a new technique of infusion dynamic ureteroscintigraphy and standard techniques of dynamic and static scintigraphy of the kidneys, radionuclide renography) were used to examine 134 patients with nephrophthisis, 61 patients with other urological diseases and 51 controls. It is shown that nephrophthisis brings urodynamic disorders and impairment of ureteral contractility. Three types of the contractile disorders are distinguished. A decline in motor function and urodynamic defects occurred also in other urological affections. Sensitive radionuclide techniques are thought valuable in examination of the urinary system and objective evaluation of urodynamic disorders. PMID- 7870725 TI - [BCG vaccination and increasing the effectiveness of treatment of post vaccination complications by the use of rifampicin and dimexide]. AB - The results of treatment for postvaccination complications were compared in 287 children (125 patients with regional lymphadenitis and 162 patients with cold abscesses). The treatment included local applications of rifampicin and dimexide solutions. Postvaccination lymphadenitis occurred significantly more frequently in children receiving BCG vaccine versus those receiving BCG-M vaccine with diminished antigenic load. Local applications of rifampicin+dimexide solution as an adjuvant treatment to isoniazid therapy of abscessed lymphadenitis permit the physician to reduce the number of puncture administration of 5% saluzid solution and decrease 2-fold the treatment duration. Similar results were obtained for cold abscess treatment. Rifampicin+dimexide applications to treat postvaccination complications in the form of lymphadenitis and cold abscesses in infiltration phase do not require local administration of saluzid, oral isoniazid. The complete resorption is reached within 1-2 months. PMID- 7870726 TI - [Effects of antibacterial preparations on growth of Mycobacterium tuberculosis in a model of primary tuberculous infection in tissue culture]. AB - Bactericidal activity of isoniazid, rifampicin and pyrazinamide in different regimens was studied on 120 mouse lung explants infected with H37Rv M. Tuberculosis. An increase in isoniazid concentration and duration of the exposure entails enhancement of its bactericidal activity. A direct correlation exists between the concentration and the exposure. Rifampicin is active mainly within first 30 minutes of its contact with the infected tissue without further augmentation of bactericidal activity with increasing concentrations and exposure. Pyrazinamide bactericidal activity is not high. Its enhancement depends rather on increasing concentrations than on duration of the exposure. PMID- 7870727 TI - [Characteristics of bacterial discharge in patients with different forms of pulmonary tuberculosis]. AB - Clinical implications of L-form pulmonary tuberculosis have been investigated in 268 patients. Of them 223 had active respiratory tuberculosis, 45 demonstrated residual disease. New cases of L-form tuberculosis were characterized by poor clinical symptoms and favourable outcomes. Association of L-forms with bacterial discharge produced apparent symptoms and progressive trends. Detection of L-forms in inactive pulmonary process indicated latent activity of tuberculosis apt to recur. PMID- 7870728 TI - [Identification of cultures of Mycobacteria cultivated using sodium salicylate medium]. AB - Sodium salicylate test is used in bacteriological practice to distinguish M. tuberculosis and M. bovis from other mycobacterial species. The species of the strains growing in sodium salicylate media are not as a rule identified. This was done using gas chromatography with cultures which had grown in Lowenstein-Jensen media with sodium salicylate and isolated from the patients admitted to the Tuberculous hospital in 1991-1993. Only 20% of the strains belonged to human mycobacteria, the others were opportunistic or saprophyte mycobacteria (M. avium, M. fortuitum, M. phlei, M. flavescens, M. vaccae, M. smegmatis), some of the cultures were not of the Mycobacterium genus, but belonged to other Actinomycetales. It is evident that with sodium salicylate test one cannot be absolutely sure of Mycobacteria isolation. The strains growing in sodium salicylate medium call for further investigations. PMID- 7870729 TI - [Formation of bronchial spasm in laboratory animals]. PMID- 7870730 TI - [Tuberculosis and pregnancy (lecture)]. PMID- 7870731 TI - [Screening for borderline disorders of carbohydrate metabolism in patients with pulmonary tuberculosis]. PMID- 7870732 TI - [Postoperative reactivation of pulmonary tuberculosis]. PMID- 7870733 TI - [Multifocal idiopathic fibrosis]. PMID- 7870734 TI - [Tuberculosis of abdominal cavity and internal genitalia in the presence of tuberculin anergy]. PMID- 7870735 TI - [Blood proteolytic systems in patients with pulmonary tuberculosis]. PMID- 7870736 TI - [Specific risk factors of the development of early period of primary tuberculous infection in children]. AB - The role of the tuberculosis contact and specific BCG immunoprophylaxis in the onset of early primary tuberculosis is investigated. Primary infection from tuberculous and healthy families depended on BCG quality, the number of BCG vaccination marks and postvaccination time. Upon the comparison of informative value of specific and nonspecific factors it was found that specific factors are leading in pathogenesis of present-day primary tuberculosis infection. PMID- 7870737 TI - [Epidemiological foci of pulmonary tuberculosis among the inmates of reformatories]. AB - Among the convicts of the Saratov region reformatories and prisons there are now 3 types of tuberculosis foci: extensive, congruent and stable. It is stated that these foci have arisen by chance as a result of misdiagnosis and poor control over persons to be treated. PMID- 7870738 TI - Lipids and cardiac arrhythmia. AB - In any discussion of lipids and heart disease it is beneficial from the outset to recognise that at least three different pathological processes may be involved. The first of these is atherosclerosis which involves the deposition of "fat" in the coronary vessels, another is thrombogenesis which describes the formation of blood clots in the coronary vessels, and the third is arrhythmia which refers to disorders in the beating of the heart which may become sufficiently serious to cause sudden cardiac death (SCD). Also it is this disturbance in the rhythmic beating of the heart which is responsible for much of the mortality from 'heart attacks' which occur 'outside-of-hospital' in societies like U.S.A., U.K. and Australia. It is this latter condition of cardiac arrhythmia which is the major concern of this review. Because it is often difficult to differentiate the role of lipids in 'heart disease' in man, it has frequently been assumed that all dietary fatty acids have similar effects on the different processes involved, and many unwarranted generalisations have been made which have led to conflicts of opinion amongst physicians and confusion in the lay public. From the animal studies discussed in this review, it is apparent that dietary fatty acids have an important role to play in determining the vulnerability of the myocardium to develop serious ventricular fibrillation (VF) and potentially lethal cardiac arrhythmia. In general, diets rich in saturated fatty acids promote a state of myocardial vulnerability, whilst diets rich in PUFA significantly diminish the probability of developing lethal disorders in cardiac rhythm when the heart is placed under pharmacological (or emotional) stress, or deprived of sufficient blood flow and supply of oxygen. Very recent experiments with the monounsaturated fatty acid (MUFA) oleic acid clearly demonstrate that, at least in rats subjected to ligation of their coronary artery, this acid is not 'neutral' as has been suggested by some for its role in atherosclerosis, but in fact is indistinguishable from saturated fatty acids in its effect in promoting arrhythmia during either regional ischaemia or reperfusion arrhythmia in this animal model of SCD.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7870739 TI - Testicular lipids. PMID- 7870740 TI - Beta-oxidation of eicosanoids. PMID- 7870741 TI - Gangliosides as influenza virus receptors. Variation of influenza viruses and their recognition of the receptor sialo-sugar chains. PMID- 7870742 TI - Efficacy of new generation antidepressants: meta-analysis of imipramine controlled studies. AB - When assessing the efficacy of a new antidepressant in comparison with a standard treatment, most clinical trials have come to the conclusion that the nullhypothesis (equal efficacy) cannot be rejected, and have not been reformulated with respect to (at least) equivalent studies. However, it cannot be concluded from this that the compared treatments have the same (or similar) efficacy, because in many of the studies the statistical power is not sufficient. Using the effect-size formula described by Glass et al. (1981), a meta-analysis were performed combining the results of comparative trials of maprotiline, mianserin, viloxazine, trazodone, nomifensine, fluvoxamine, and fluoxetine, performed according to similar objectives and designs (similar patient selection, double-blind, randomized, etc.) and with imipramine as reference compound. Together with the results of a former meta-analysis of amitriptyline-controlled studies (Moller and Haug, 1988) the present investigation indicates differences in efficacy, which in the case of most of the new generation antidepressants is similar to the reference compounds imipramine and amitriptyline. PMID- 7870743 TI - Pharmacopsychological effects of oxazepam and kava-extract in a visual search paradigm assessed with event-related potentials. AB - The effects of oxazepam and a standardized extract of kava-roots (WS1490, W. Schwabe, Karlsruhe) on reaction time and event-related potentials (ERPs) were investigated in a visual search paradigm using a double-blind design in young, healthy males. Significant effects of oxazepam were obtained in a number of psychometric tests as well as search time and quality. Several ERP components of different latency, topography and functional significance were affected by the medications. Oxazepam led to a reduction of the amplitude of the parietal N1, frontal N2, posterior contralateral N2, and occipital P3 components. WS 1490 was associated with a greater posterior N1, posterior contralateral N2, and occipital P3. The effects are discussed in the light of the functional properties of the components and provide clues as to the psychological site of action of the drugs. PMID- 7870744 TI - Somatoform disorders--diagnostic concept, controlled clinical trials, and methodological issues. AB - The paper summarizes the concept of somatoform disorders, which was first introduced in the Diagnostic and Statistical Manual of Mental Disorders in its third edition in 1980. The relevant clinical trials related to this concept are reviewed. On the basis of this experience, the present study discusses methodological requirements for clinical trials, including inclusion and exclusion criteria, measurements of efficacy and safety, and statistical considerations, in the hope that this will stimulate the use of this diagnostic entity in the future. PMID- 7870746 TI - Benzodiazepines and the psychopathology of catatonia. AB - This paper focuses attention on the importance of psychopathological analysis in the evaluation of benzodiazepine treatment response in catatonia. The authors report the successful reversal of the catatonic syndrome with small doses of benzodiazepine in two patients who demonstrated stupor and excitement respectively. Viewing the catatonic syndrome from a nosological vantage point, they attempt to demonstrate that its response to benzodiazepines is partly determined by the underlying psychiatric disorder. Discussing the psychopathological and clinical concept of catatonia, the authors argue that revision of the legacy of Jaspers and the Wernicke-Kleist-Leonhard school may help to disentangle the current terminological and conceptual ambiguity and confusion. PMID- 7870747 TI - Fluoxetine-induced sexual dysfunction: a dose-dependent effect? PMID- 7870745 TI - Blood levels of mianserin and amitriptyline and clinical response in aged depressed patients. AB - Steady-state plasma levels of mianserin, amitriptyline, and nortriptyline were determined by HPLC in two groups of elderly depressed patients who underwent a 5 week treatment with mianserin (60 mg/day in three oral doses) or amitriptyline (75 mg/day in three oral doses). Both treatments proved to be effective in reducing depressive symptoms. In the mianserin group, responder patients had steady-state plasma concentrations of mianserin higher than nonresponders. No relationship was found between amitriptyline, nortriptyline, or amitriptyline+nortriptyline plasma levels and clinical response in amitriptyline treated patients. PMID- 7870748 TI - Remembering John. PMID- 7870749 TI - Reliability, validity, and responsiveness of functional tests in patients with total joint replacement. AB - BACKGROUND AND PURPOSE: High-quality measurements are needed to develop meaningful clinical practice databases to assess the effectiveness of physical therapy. This study determined the reliability, validity, and responsiveness of measurements obtained with five functional tests graded with the newly developed Iowa Level of Assistance Scale. SUBJECTS AND METHODS: Eighty-six patients with total hip or knee replacements were tested at various time periods during their hospitalization. Patients were tested for five functional activities by four therapists to establish the reliability and test responsiveness. The Harris Hip Rating Scale was administered to assess the validity of the functional score. RESULTS: The weighted Kappa statistic supported good intratester (K = .79-.90) and moderate intertester (K = .48-.78) reliability. The correlation between the Harris Hip Rating Scale scores and the total functional scores was high (r = .86). The total functional score was responsive to 4 days of therapy postoperatively. CONCLUSION AND DISCUSSION: The assessment of function using the Iowa Level of Assistance Scale was shown to be highly reliable, valid, and responsive in patients following total hip or knee replacements. PMID- 7870750 TI - Disability and functional status in patients with low back pain receiving workers' compensation: a descriptive study with implications for the efficacy of physical therapy. AB - BACKGROUND AND PURPOSE: The efficacy of a physical therapy outpatient program with multiple interventions to treat low back pain in subjects receiving workers' compensation was examined. The primary purpose of the study was to describe the level of disability, physical impairment, and rate of return to work for compensated patients. SUBJECTS: One hundred thirty-eight patients (84 male, 54 female), aged 17 to 63 years (mean = 38, SD = 10), were evaluated prospectively. METHODS: Subjects were assessed initially (INA) and were reevaluated 1 month later (1MO) and again at the time of discharge (DC). The Oswestry disability score, fingertip-to-floor distance during forward bending, maximal isometric lift, and work status were described as outcomes. Subjects were grouped based on compliance, chronicity, and leg symptoms. Each disability/impairment outcome was analyzed with paired t tests (INA versus 1MO and INA versus DC). The frequency of subjects returning to work across groups was evaluated with a chi-square analysis corrected for unequal group sizes. RESULTS: Overall, there was improvement in each dependent measure at 1MO and DC compared with the INA. Subjects with high compliance had a 10% reduction in mean disability at 1MO and a 12% reduction in mean disability at DC compared with the INA. The low-compliance group, in contrast, showed less than a 5% reduction in mean disability at both the 1MO and DC assessments compared with the INA. The magnitude of improvement in disability status, forward bending, and maximal lift was approximately two to three times greater for subjects with acute symptoms compared with those with chronic symptoms. The increase in mean forward bending for subjects without leg symptoms was over twice as large as the increase in forward bending for subjects with leg symptoms. Seventy-five percent of the subjects followed at DC (30 out of 40) were released to work in some capacity. There was no association between compliance or presence of leg symptoms and work status at DC. Eighty percent of the subjects with acute symptoms, however, were working at the time of DC compared with 44% of those with chronic symptoms. CONCLUSION AND DISCUSSION: Compliance, chronicity, and leg symptoms are all factors that can affect the outcome of physical therapy. The positive outcomes for subjects who complied with therapy suggest that a physical therapy program with multiple interventions may decrease disability and impairment. PMID- 7870751 TI - Physical therapy management of isolated serratus anterior muscle paralysis. AB - This case report presents a patient who developed right shoulder pain following strenuous upper-extremity exercise. Approximately 6 weeks later his pain resolved, he noticed persistent right upper-extremity weakness. He was referred to physical therapy for evaluation and treatment. Physical therapy evaluation revealed isolated serratus anterior muscle paralysis. A long thoracic neuropathy was subsequently confirmed by electromyographic testing. The etiology, pathophysiology, and pathokinesiology of serratus anterior muscle paralysis are reviewed. A case is presented, illustrating how the clinical decision making is based on the pathokinesiology and pathophysiology. The patient was followed over the course of 17 months and has recovered full right shoulder active range of motion. His serratus anterior muscle strength has increased to Good minus, and he reports significantly improved functional use of the upper extremity. PMID- 7870752 TI - Use of a spinal model to quantify the forces and motion that occur during therapists' tests of spinal motion. AB - BACKGROUND AND PURPOSE: Despite the widespread use of spinal mobilization, little is known about the forces used or the accuracy of therapists in estimating the forces they use in administering the technique. The purposes of this study were to quantify the forces used and to determine the accuracy of therapists in applying forces on a mechanical model. SUBJECTS: Ten physical therapists participated. METHODS: A spinal model was used to measure applied force and displacement under different conditions of stiffness. The therapists applied oscillatory posteroanterior mobilizations to the model under three different conditions of stiffness. RESULTS: Mean peak forces across grades and stiffness levels ranged between 57.59 and 178.27 N. The forces were generally lower in the least stiff condition. Displacement varied with stiffness and mobilization grade. In the least stiff condition, the mean displacement varied between 2.25 and 3.45 mm for grades 1 to 4, respectively. CONCLUSION AND DISCUSSION: Inter-therapist variability was high, and there was a systematic bias in underestimating the magnitude of applied force and in overestimating motion. The variability in force application and the general overestimation of motion detection may explain the poor reliability of measurements obtained with clinical tests based on motion palpation. PMID- 7870753 TI - Research and the cumulation of knowledge in Physical Therapy. AB - BACKGROUND AND PURPOSE: Published research contributes to the knowledge base that distinguishes one discipline from another. More research is now published in the physical therapy journals, but concerns with the profession's knowledge base continue. SUBJECTS: The study examined citations from 78 clinical articles published and indexed on three thematic areas in Physical Therapy between 1951 and 1990. METHODS: Unique items and multiple-cited items were identified and counted and their sources ascertained. Linkages among multiple-cited items in each thematic area were identified and described. RESULTS: Most cited items were unique and not from the physical therapy literature. Few linkages were identified among the clinical articles. CONCLUSION AND DISCUSSION: The lack of evidence of cumulation or of coherence among the articles examined and the extent of reliance on non-physical therapy sources suggest that concerns with the knowledge base of the profession are well founded. PMID- 7870754 TI - Portable versus home stimulators. PMID- 7870755 TI - Flexibility or muscle length? PMID- 7870756 TI - Cyriax's passive motion tests. PMID- 7870757 TI - Craniosacral controversy. PMID- 7870758 TI - Socially responsible reform. PMID- 7870759 TI - Protein structure modelling of the bacterial light-harvesting complex. AB - Protein structure modelling offers a method of obtaining 3-dimensional information that can be tested and used to plan mutagenesis experiments when a crystallographically determined structure is not available. At its simplest a model may consist of little more than a secondary structure prediction coupled with a determination of the likely regions of transmembrane/membrane surface/globular configuration. These methods can yield an interesting topology map of the protein, which places the residues in their likely positions with respect to, for example, the membrane interface. If it is a member of a large family of related proteins then aligned protein sequences can be used to predict the residues that have an important function as these will be largely conserved in the alignments. Using all these methods a model can be constructed (using for example, the Nicholson Molecular Modelling Kit) to visualize the proposed structure in three dimensions following the premise of good design, that is, avoiding obvious steric clashes, packing of helices in a realistic manner, observing the correct H-bond lengths, etc. In this latter exercise the review of Chothia (Annu. Rev. Biochem. 53, 537-572, 1984) of the principles of protein structure is particularly helpful as it clearly sets out how proteins pack and their preferred configuration. There is a wealth of information about individual amino acid conformational preferences and observed frequencies of occurrence in known protein structures, which can help decide how the residues in the model can be oriented. In this article we have collated the various protein models of the bacterial light-harvesting complexes and present our own model, which is a synthesis of the available biophysical data and theoretical predictions, and show its performance in explaining recent results of site-directed mutants of the LH1 and LH2 light-harvesting complexes of Rhodobacter sphaeroides. PMID- 7870760 TI - Light quenching of fluorescence: a new method to control the excited state lifetime and orientation of fluorophores. AB - Experimental studies have recently demonstrated that fluorescence emission can be quenched by laser light pulses from modern high-repetition rate lasers, a phenomenon we call "light quenching." In this overview article, we describe the possible effects of light quenching on the steady-state and time-resolved intensity and anisotropy of fluorophores. One can imagine two classes of experiments. Light quenching can occur within the single excitation pulse, or light quenching can be accomplished with a second time-delayed quenching pulse. The extent of light quenching depends on the amplitude of the emission spectrum at the quenching wavelength. Different effects are expected for light quenching by a single laser beam (within a single laser pulse) or for a time-delayed quenching pulse. Depending upon the polarization of the light quenching beam, light quenching can decrease or increase the anisotropy. Remarkably, the light quenching can break the usual z-axis symmetry of the excited state population, and the measured anisotropy (or polarization) depends upon whether the observation axis is parallel or perpendicular to the propagation direction of the light quenching beam. The polarization can increase to unity under selected conditions. Quenching with time-delayed light pulses can result in step changes in the intensity or anisotropy, which is predicted to result in oscillations in the frequency-domain intensity and anisotropy decays. These predicted effects of light quenching, including oscillations in the frequency-domain data, were demonstrated to occur using selected fluorophores. The increasing availability and use of pulsed laser sources requires consideration of the possible effects of light quenching and offers the opportunity for a new class of two-pulse or multiple-pulse time-resolved experiments where the sample is prepared by the excitation pulse and subsequent quenching pulses to modify the excited state population, followed by time- or frequency-domain measurement of the optically prepared excited fluorophores. PMID- 7870761 TI - 4'-Aminomethyl-4,5',8-trimethylpsoralen photochemistry: the effect of concentration and UVA fluence on photoadduct formation in poly(dA-dT) and calf thymus DNA. AB - The photochemistry of 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT) with poly(dA dT) and calf thymus DNA was studied. The extent of photoadduct formation and the distribution of photoadducts (3,4- and 4',5'-monoadducts and crosslinks) were determined by liquid scintillation analysis and HPLC, respectively. The adducts were characterized on the basis of their UV absorption spectra and mass spectral analysis. The high DNA binding constant for AMT (1.5 x 10(5) M-1) led to a high fraction of intercalated molecules, which contributed to the high level of AMT photoadduct formation, as many as 102 adducts per kilobase pair. In addition, there is a distinct difference in the adduct distribution compared to the previously studied 8-methoxypsoralen (8-MOP). Under the conditions employed for the photochemical studies, virtually all of the AMT molecules in solution are intercalated, occupying 25% of the base pair sites. Under similar conditions, 8 MOP molecules occupied 10 times fewer sites. Thus, for AMT, DNA base pair sites other than 5'TA, the well-characterized strong binding for psoralens in general, are an additional target for photomodification, which results in the formation of a higher percentage of monoadducts. The proportion of photoadducts formed was virtually independent of AMT concentration and UVA (320-400 nm radiation) fluence. PMID- 7870762 TI - Photochemical sensitization by azathioprine and its metabolites. Part 3. A direct EPR and spin-trapping study of light-induced free radicals from 6-mercaptopurine and its oxidation products. AB - Sunlight has been implicated in the high incidence of skin cancer found in patients receiving 6-mercaptopurine (PSH) in the form of its pro-drug azathioprine. In this study we have used EPR spectroscopy in conjunction with the spin-trapping technique to determine whether PSH and its metabolic or photochemical oxidation products generate highly reactive free radicals upon UV irradiation. When an aqueous anaerobic solution (pH 5 or 9) of PSH (pKa = 7.7) and either 2-methyl-2-nitrosopropane (MNP) or nitromethane (NM) were irradiated (lambda > 300 nm) with a Xe arc lamp, the corresponding purine-6-thiyl (PS.) radical adduct and the reduced form of the spin trap (MNP/H. or CH3NO2.-) were observed. However, no radical adducts were detected when PSH and 5,5-dimethyl-1 pyrroline-N-oxide (DMPO) were irradiated (lambda = 320 nm) in oxygen-free buffer. These findings suggest that PSH does not photoionize but that instead MNP and NM are reduced by direct electron transfer from excited state PSH, 1.3(PSH)*. In aerobic solution, oxygen can act as an electron acceptor and the O2.- and PS. radicals are formed and trapped by DMPO. 6-Mercaptopurine did photoionize when irradiated with a Nd:YAG laser at 355 nm as evidenced by the appearance of the DMPO/H.(eq- + H+) adduct, which decreased in intensity in the presence of N2O. 1.3(6-Mercaptopurine)* oxidized ascorbate, formate and reduced glutathione to the corresponding ascorbyl, CO2.- or glutathiyl radicals. The photochemical behavior of 6-thioxanthine and 6-thiouric acid was similar to PSH. However, the excited states of these metabolic oxidation products exhibited stronger reducing properties than 1.3(PSH)*.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870763 TI - Absorption spectrum of hematoporphyrin derivative in vivo in a murine tumor model. AB - Time-resolved reflectance was used to measure the absorption spectrum of hematoporphyrin derivative (HpD) in vivo in a murine tumor model. Reflectance measurements were performed in the 600-640 nm range on mice bearing the L1210 leukemia. Then the animals were administered 25 mg/kg body weight of HpD intraperitoneally. One hour later the reflectance measurements were repeated. Fitting of the data using the diffusion theory allowed assessment of the absorption coefficient before and after the administration. As a difference between the latter and the former data, the in vivo absorption spectrum of HpD was evaluated. Maximum absorption was measured at 620-625 nm. Similar spectral behavior was obtained for HpD in solution in the presence of low-density lipoproteins. PMID- 7870764 TI - Molecular basis of drug phototoxicity: photosensitized cell damage by the major photoproduct of tiaprofenic acid. AB - Tiaprofenic acid is a photosensitizing nonsteroidal anti-inflammatory drug, whose major photoproduct (decarboxytiaprofenic acid) is also a potent photosensitizer. Because of the lack of the carboxylate moiety, this photoproduct is more lipophilic and might bind more efficiently to cell membranes, thereby causing phototoxic damage. To verify the feasibility of this hypothesis, we have prepared the 3H-labeled analogs of tiaprofenic acid and its photoproduct and examined the binding, persistence and phototoxicity of the photoproduct using poorly metabolizing (fibroblasts) and actively metabolizing cells (hepatocytes). The photoproduct of tiaprofenic acid accumulates in both cell types as it is formed. Upon removal of the photoproduct from the culture medium, it rapidly disappears from hepatocytes but not from fibroblasts. Consequently, irradiation of fibroblasts previously incubated with the photoproduct and kept in culture in the dark for 20 h results in generalized cell damage while this effect is not observed in hepatocytes. Because of its long persistence in poorly metabolizing skin cells and its reluctance to photobleaching, the formation of this photoproduct in skin may be of relevance to explain the in vivo phototoxicity of tiaprofenic acid. PMID- 7870765 TI - Photoactive terthiophenes: the influence of serum on anti-HIV (human immunodeficiency virus) activities. AB - A number of carboxylic acid derivatives of the photoactive terthiophene, alpha terthienyl, were found to possess impressive UVA-dependent activity against the human immunodeficiency virus, HIV-1; but only when assayed in the absence of serum, indicating that the latter contained interfering components. Good antiviral activity required a high rate of singlet oxygen production, in accordance with previous observations on thiophenes. PMID- 7870766 TI - APS intersociety meeting. Regulation, Integration, Adaptation: A Species Approach. San Diego, California, October 29-November 2, 1994. Abstracts. PMID- 7870767 TI - Prefabrication of a secondary TRAM flap. AB - A secondary TRAM flap was prefabricated in a rat model using the rectus muscle. The right rectus muscle was elevated as an inferiorly pedicled muscle flap in one experimental group (n = 6) and as a superiorly pedicled muscle flap in a second group (n = 5) and then sandwiched between a silicone sheet and the abdominal skin. Two weeks later, the abdominal skin and attached rectus muscle were elevated over the silicone sheet as a secondary TRAM flap. The surviving skin paddle areas of these prefabricated TRAM flaps were compared with superiorly (n = 7) and inferiorly (n = 8) pedicled TRAM flaps in a control group. One-way analysis of variance did not show significant differences between groups (p = 0.07). TRAM flap prefabrication in the rat model yields a skin paddle survival area comparable to that of a conventional TRAM flap, and it is possible to perform this procedure without using the anterior rectus sheath. PMID- 7870768 TI - A clinical and histologic comparison between free temporoparietal and scapular fascial flaps. AB - It is universally accepted that the fascial flap is one of the best reconstructive strategies for contour and tendon-gliding function. In this study we compare the free temporoparietal fascial flap (n = 20) and the free scapular fascial flap (n = 6) mainly for these reconstructions and discuss their characteristics, including different clinical applications and histologic examination. Our histologic analysis reveals that the free temporoparietal fascial flap has a potential like a muscle flap; moreover, it is very thin. The free scapular fascial flap is very rich in adipose tissues to prevent adhesion between the flap and underlying tissues. Both flaps in our experience can bring satisfaction to the recipient site, but the donor site of the free temporoparietal fascial flap sometimes suffers from conspicuous widened scars in short-haired patients, and the scapular fascia has a tendency to be thicker in obese patients. Therefore, we recommend using the free temporoparietal fascial flap for women, who tend to have more fat and longer hair, and the free scapular fascial flap for men, who tend to be lean and shorten their side hair. PMID- 7870769 TI - Aesthetic guidelines in genioplasty: the role of facial disproportion. AB - It has been demonstrated previously that many individuals requesting chin enlargement have small or retruded mandibles. A weak chin may be only one aspect of this particular class II skeletal deformity, the other components being a procumbent, retrusive lower lip, excessive labiomental fold depth, and decreased to normal lower face height. To avoid unaesthetic results, the chin should not be advanced beyond the retrusive lower lip, the only component over which osseous genioplasty has no control. This may result in residual sagittal "weakness" of the lower face, for which visual compensation can be achieved by vertical overelongation of the chin. Thirty-two patients requesting chin enlargement presented with the aforementioned class II deformity. Twenty patients had decreased lower face height and 12 patients had normal lower face height. Preoperative soft-tissue cephalometric analysis documented physical findings. The extent of sagittal chin movement was planned to advance the soft-tissue pogonion no further than the lower lip. Vertical chin movement was intentionally designed to overelongate the lower face relative to the midface in all patients. Radiographs were repeated at a mean 8.2 months following surgery to document skeletal displacements. Mean chin advancement was a modest 4.2 mm (2- to 7-mm range), and chin vertical displacement was a mean 7.9 mm (5.5- to 9-mm range). All patients had residual sagittal disproportion of the pogonion relative to the subnasale (-7.6 mm mean) and newly created vertical disproportion with mean lower face heights of 69.8 mm compared with mean midface heights of 64 mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870770 TI - The chin: skeletal and soft-tissue components. AB - The quantity of soft tissue overlying the symphysis menti affords an important attribute that can aid in determination of the correct surgical approach for optimal facial harmony. Xerograms of the facial profile of 100 patients with normal occlusion were analyzed by accepted radiographic cephalometric techniques. The relative contribution of skeletal structures and soft tissue of the chin was evaluated. All linear measurements were noted to be larger in males than in females, but in both groups, facial features were in proportion. In both males and females, the average thickness of the soft tissue overlying the symphysis menti progressively increased from the B point to midway between the B point and the pogonion. The soft tissue at the pogonion was thinner than at the B point. The soft tissue over the chin in males was significantly thicker than in females in all areas measured. When compared with patients over 60 years of age, the soft tissue at the B point was significantly thinner in patients 50 years of age and younger (p = 0.005), while the soft tissue at the pogonion was significantly thinner in patients 40 years of age and younger (p = 0.04). Pseudomacrogenia was noted in 6 percent of the patients, a diagnosis only possible with cephalometric analysis. An understanding of the relative contribution of the soft tissue to the chin can aid in the diagnosis and appropriate surgical management of chin incongruity. Furthermore, there is significant variation in skin thickness, which will influence the soft-tissue response to skeletal alteration. This has to be considered in planning a predictable surgical result. PMID- 7870771 TI - Experience with isovolemic hemodilution in extensive head and neck surgery. AB - Isovolemic hemodilution was performed on 30 American Society of Anesthesiologists (ASA) class I patients during extensive surgical procedures in the head and neck region using 3.5% polygeline (Haemaccel, Hoechst) as hemodiluent. The mean total surgical blood loss was 831.66 +/- 291.04 ml, and mean total blood drained was 1021.66 +/- 187.38 ml. The heart rate, mean arterial pressure, and central venous pressure showed insignificant variation. Fall in packed cell volume and hemoglobin was highly significant with hemodilution and with retransfusion. The values increased and were comparable to pre-hemorrhage values on the day of discharge. No significant change was found in arteriovenous oxygen saturation difference and arteriovenous oxygen content difference. The need for homologous blood transfusion was avoided in all patients. There was no significant complication in terms of wound healing or flap necrosis. The technique was found to be safe, and therefore, we recommend this in all extensive surgical procedures in the head and neck region in patients deemed to be fit for the procedure. PMID- 7870772 TI - Craniofacial development in rats with early resection of the zygomatic arch. AB - Eighty-two-day-old male Wistar rats were selected to study the pattern of craniofacial growth following resection of the zygomatic arches. Rats were divided into three groups: group I (n = 14), the control group; group II (n = 15), with unilateral resection of the zygomatic arch; and group III (n = 8), with bilateral resection. Direct dry skull and cephalometric measurements show increased facial projection and decreased transverse facial width on the side of the resected arch. If the results are extrapolated to the growth pattern of patients with the Treacher Collins syndrome, we can conclude that the zygomatic arch acts as a "moderator" in the morphologic development of the face. PMID- 7870773 TI - Melanoma of the scalp: the invisible killer. AB - A series of 20 patients (15 men and 5 women) suffering from malignant melanoma of the scalp is reported. Their epidemiologic data and outcome are described. The ages ranged from 48 to 78 years (mean 63 years). Analysis of the cases demonstrated that lesions occurring posterior to the tragal line (in hair-bearing area) have the worst prognosis. The 5-year survival rate was poor; 12 patients died within this period. Two representative cases are described, and the preventable aspects of the disease are emphasized. PMID- 7870774 TI - Inframammary crease ligament. AB - This study was designed to clarify and define the anatomic components of the inframammary crease in the female breast. Thirteen blunt dissections of the female breast were performed in cadavers and one dissection was performed in a living patient undergoing mastectomy. During the course of these dissections, a ligament was identified. This ligament originates from the fifth rib periosteum medially and the fascia between the fifth and sixth ribs laterally. The ligament inserts distally into the deep dermis of the inframammary skin fold. Histologic sections confirmed the proximal bony origin of this structure. In three cadavers, the contralateral breast was studied as it pertains to transaxillary subpectoral mammaplasty using the Agis-Dingman dissector (Padgett Instruments, Kansas City, Mo.). If too forceful a sweep were made in the inferior portion of the dissection, the ligament would be disrupted. This separation of the ligament from its origin could lead to the "double-bubble" phenomenon. Further, the horizontal position of this ligament determines the medial versus lateral fall of the ptotic breast. PMID- 7870775 TI - Total muscle coverage of a breast implant is possible through the transaxillary approach. AB - In breast augmentation through the transaxillary subpectoral approach, previous studies have indicated that the implant was only covered by muscle to the upper third of its surface. In my experience with our method of dissection of the implant pocket, I had come to a different opinion about muscle coverage of the implant. In order to confirm the position of the implant, I have undertaken an anatomic study in 10 fresh female cadavers. A transaxillary subpectoral breast augmentation was performed, followed by an anatomic dissection of both sides. In all 20 implantation sites, it was found that the implant was totally covered by muscle. The muscles involved were the pectoralis major, serratus anterior, and obliquus abdominis externus. These findings have been confirmed in the clinical setting by endoscopic photographs. Since it is documented that total muscle coverage produces fewer capsular contractures, as well as fewer steroid-related complications, and considering the superior position of the scar, I today consider this approach to be most useful. PMID- 7870776 TI - Electron probe microanalysis of silicon and the role of the macrophage in proximal (capsule) and distant sites in augmentation mammaplasty patients. AB - Electron probe x-ray microanalysis was used to locate silicon (Si) within macrophages from 12 women who had previously undergone polymer prosthesis augmentation or reconstruction. Silicon was identified within macrophages and extracellularly in all fibrous breast capsules. In four women with arthritic joint pain and one woman with sclerodermatous skin lesions, silicon also was identified within macrophages residing in joint synovium and skin, respectively. It is suggested that the silicon-laden macrophages observed in the remote lesions may have accumulated silicon from other macrophages that had previously resided in the connective-tissue capsule around the silicone breast implants. PMID- 7870777 TI - An anatomic study for a vascularized bone flap of femur. AB - The anatomy of the nutrient vessels of the shaft of the human femur was studied in a series of 20 dissections in 10 preserved cadavers and 8 clinical stereoscopic angiograms of the femoral region in 7 adult patients. The number and external diameter of the nutrient artery and the distance of the nutrient vessel from the greater trochanter and the origin of the profunda femoris artery were measured. A single or two nutrient vessels of large caliber originated from the perforating branches of the profunda femoris artery constantly entered at the points along the linea aspera of the femur. The average distance of the nutrient artery from the point where the profunda femoris artery arose from the femoral trunk, which means length of the vascular pedicle of a bone flap, was over 11 cm. We foresee the future use of a vascularized bone flap of the femur combined with the surrounding muscle and the lateral thigh fasciocutaneous flap based on the profunda femoris vascular system. PMID- 7870778 TI - The time sequence of the delay phenomenon: when is a surgical delay effective? An experimental study. AB - We have shown previously that when a flap is delayed, the maximal anatomic effect on the arterial side of the circulation is focused at the level of the reduced caliber choke vessels that link adjacent vascular territories. These anastomotic vessels were noted to increase in size to the dimension of true anastomoses. However, we did not define when this occurred. The present experiment therefore was designed to elucidate the chronologic sequence of events that occur in the "choke" vessels using a rabbit flank skin flap as the experimental model. A long two-territory osteocutaneous flank flap was designed on one side of each rabbit (n = 30), with the opposite unoperated side serving as a control. The flap was elevated and sutured back in place. At various times postoperatively, namely, 1 (n = 2), 2 (n = 2), 3 (n = 2), 4 (n = 2), 6 (n = 2), 8 (n = 2), 12 (n = 2), 24 (n = 2), 48 (n = 2), and 72 (n = 2) hours and 7 days (n = 10), the animals were sacrificed, and total-body arteriograms were obtained using a lead oxide mixture. The density and size of the choke arteries between the territories in the flap and their counterparts on the control side were assessed by histologic analysis (n = 3). We observed a sequential dilation of choke vessels during the delay period. In particular, we found that the vessels increased rapidly in size between the 48- and 72-hour studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870779 TI - Carpal tunnel release using limited direct vision. AB - A novel method to release the carpal tunnel is presented. It combines the advantages of endoscopic and open techniques while utilizing standard instruments. A lighted Killian nasal speculum is introduced between the palmar fascia and the transverse carpal ligament. The ligament is incised under direct vision. The procedure was performed in 28 cadaver hands and followed by inspection utilizing the open method through an interthenar incision. The transverse carpal ligament was completely divided in all hands without nerve or tendon injury. The superficial palmar arch was injured in one hand (3.6 percent). The advantages, disadvantages, pitfalls, and results are discussed. The technique is simple and effective, employs inexpensive instruments, and has a low complication rate. PMID- 7870780 TI - Syndactylic toe transfer for fingertip reconstruction. AB - In the case of multiple fingertip reconstruction requiring toe transfer, double toes can be elevated in the syndactylic fashion with a single vascular pedicle for transfer, followed by separation a few weeks later. The biggest advantage of this procedure is that the problem of limitation of recipient arteries for multiple toe transfer is solved. We reconstructed fingertips of three patients by this procedure with three variations based on combinations between the wrap around flap and whole-toe transfer. All three patients survived completely and achieved an aesthetically pleasing result. This report introduces the concept and technique of the syndactylic toe transfer for fingertip reconstruction. PMID- 7870782 TI - What physicians can learn from President Clinton's legal problems. PMID- 7870781 TI - Desmoplastic malignant melanoma: a clinicohistopathologic review. AB - Desmoplastic malignant melanoma is an unusual variant of cutaneous melanoma. Arising from either an occult or recognized superficial melanotic lesion, it evolves into an aggressive, locally recurrent and frequently metastasizing, deep, hard, fibrous tumefaction. A highly confusing clinical and histologic picture makes accurate diagnosis especially difficult. Appropriate treatment is often delayed until time of recurrence. Prognosis is invariably poor if the tumor is not adequately treated primarily. Close follow-up is essential. Since its original description by Conley et al. in 1971, in which 7 cases were presented, fewer than 150 additional cases have been cited. We provide a detailed report of 11 cases of this distinct histopathologic entity. Clinical course, histopathology, surgical management, and prognosis are discussed. It is our hope that this comprehensive review will instill a high index of suspicion among surgeon and pathologist alike, enabling earlier diagnosis and definitive therapy. PMID- 7870783 TI - Rhinophyma, associated with carcinoma, treated successfully with radiation. AB - Two patients with significant rhinophyma with simultaneous basal cell carcinomas had complete control of both conditions by orthovoltage x-ray therapy. The use of this modality in the control of rhinophyma alone should be considered. PMID- 7870784 TI - Intraductal migration of silicone from intact gel breast prostheses. AB - This case presents a previously undocumented complication of silicone gel prostheses in which silicone accumulated in the lactiferous ductal system of the breast with the underlying prostheses being intact. It demonstrates the disconcerting potential of silicone to migrate through tissue planes that are not disrupted. It also highlights the fact that a great deal of knowledge about the body's interaction with silicone still needs to be ascertained. PMID- 7870785 TI - Iatrogenic nostril stenosis: aesthetic correction using a vestibular labial mucosa flap. AB - Nostril stenosis is an infrequent finding that often has an iatrogenic cause. It is a very difficult problem to resolve and usually requires several months of prosthetic support in order to counteract the recurrence of internal scarring and shrinking. We present a 4-year-old child with a monolateral iatrogenic nostril stenosis. A satisfactory and stable correction was obtained using a "piercing" flap taken from the labial vestibule. The use of a nasal stent (not placed immediately and worn only at night) was necessary for only 2 months. This technique has a number of advantages: the absence of external scars, little or no tendency to recurrence due to the absence of contraction provided by the well vascularized flap tissue, and the ease and rapidity of the surgical procedure. PMID- 7870786 TI - Simple and useful instruments in cartilage grafting. PMID- 7870787 TI - Medical-grade tattooing to camouflage depigmented scars. AB - Scars are apparent, in part, as a result of the loss of cutaneous pigments. This disfigurement can be concealed successfully with medical-grade tattooing. This treatment was evaluated on 39 scars in 18 patients. The procedure was performed under local anesthesia on an outpatient basis, unless carried out in conjunction with other procedures. The medical-grade tattooing dye was selected during the initial consultation to match the skin color in a natural light ambiance. An electric tattooing machine was used to implant the medical-grade dye in the dermis. Successful concealment of the depigmented scars was achieved subsequent to the first procedure in all but 4 patients. Two of the 4 patients exhibited inadequate camouflage of scars, and 2 were judged to have excess pigmentation following treatment. Both these conditions required revision. PMID- 7870788 TI - Frontal sinus obliteration: in search of the ideal autogenous material. AB - The controversies concerning obliteration of the frontal sinus in response to trauma, infection, or tumor growth are long-standing (1913 to the present) and related to the field of training of the surgeon. Successful frontal sinus obliteration requires (1) meticulous removal of the frontal sinus mucosa, (2) removal of the inner cortex of the sinus wall, and (3) permanent occlusion of the nasofrontal duct. It is significant to note that most of the clinical literature relates to management of infected sinuses (sinusitis) and most experimental studies are done on uninfected, unfractured feline models. Therefore, no direct reference can be made to the management of the fractured frontal sinus. The techniques in current use are autologous implantation of fat, bone, and muscle, along with the technique of spontaneous osteogenesis. These techniques are all effective when the preceding guidelines are followed, with the only real advantage being that the spontaneous osteogenesis avoids the problem of donor site morbidity, which has been as high as 5 percent. This factor makes the osteogenesis technique the method of choice for frontal sinus obliteration. This literature review provides the surgeon with the objective data available for optimal frontal sinus obliteration. PMID- 7870789 TI - Frontal sinus obliteration: a comparison of fat, muscle, bone, and spontaneous osteoneogenesis in the cat model. AB - The obliteration of the frontal sinus is frequently necessary in the appropriate treatment of trauma, chronic infection, and benign tumors, but the various methods have not been directly compared previously. This study compares four treatment groups (seven cats per group) specifically of implantation of autologous fat, muscle, and bone and spontaneous osteogenesis done using a strictly standardized operative technique in an unfractured, uninfected feline frontal sinus model. All methods studied were effective in sinus obliteration; however, significant morbidities occurred at the donor sites when autologous tissue transplantation was used. Therefore, spontaneous osteogenesis appears to be the method of choice for frontal sinus obliteration. PMID- 7870790 TI - Death of a tooth after rhinoplasty. PMID- 7870791 TI - An alternative method of reconstructing one-third to one-half of the auricular circumference. PMID- 7870793 TI - A modest proposal to help alleviate some of the malpractice mess. PMID- 7870792 TI - Multiple enchondroma. PMID- 7870794 TI - Inflatable breast implants. PMID- 7870795 TI - Simultaneous deep-plane face lift and trichloroacetic acid peel. PMID- 7870796 TI - Full-thickness facial chemical burn from a "50% TCA" peel. PMID- 7870798 TI - Nasolabial fold. PMID- 7870797 TI - Tumescent technique with local anesthesia for liposuction. PMID- 7870799 TI - Survey of Houston plastic surgeons. PMID- 7870800 TI - Bodyboard-related orbital fractures. PMID- 7870801 TI - Understanding laser-tissue interactions helps predict clinical effects. PMID- 7870802 TI - Decisions, decisions, decisions. PMID- 7870803 TI - "Taking the pulse" of the radial forearm flap. PMID- 7870804 TI - Laser-assisted nerve repair. PMID- 7870806 TI - Abdominoplasty with double excision. PMID- 7870805 TI - Consensus of opinion regarding capsulectomy. PMID- 7870807 TI - Tumescent technique in liposuction. PMID- 7870808 TI - The oral boards. What to study? That is the question! PMID- 7870809 TI - Faces, hips, and steroids. PMID- 7870810 TI - Template for a zigzag coronal incision. PMID- 7870811 TI - Modification of Mustarde technique for correction of epicanthus in Asian patients. PMID- 7870812 TI - Molecular and physiological responses to abscisic acid and salts in roots of salt sensitive and salt-tolerant Indica rice varieties. AB - The Indica rice (Oryza sativa L.) varieties Pokkali and Nona Bokra are well-known salt tolerance donors in classical breeding. In an attempt to understand the molecular basis of their tolerance, physiological and gene expression studies were initiated. The effect of abscisic acid (ABA) on total proteins in roots from 12-d-old seedlings of Pokkali, Nona Bokra, and the salt-sensitive cultivar Taichung N1 were analyzed on two-dimensional gels. The abundance of ABA-induced proteins was highest in the most tolerant variety, Pokkali. Three ABA-responsive proteins, present at different levels in roots from tolerant and sensitive varieties, were further characterized by partial amino acid analysis. A novel histidine-rich protein and two types of late embryogenesis abundant (LEA) proteins were identified. Protein immunoblotting revealed that the levels of dehydrins and group 3 LEA proteins were significantly higher in roots from tolerant compared with sensitive varieties. Endogenous ABA levels showed a transient increase in roots exposed to osmotic shock (150 mM NaCl). Peak ABA concentrations were 30-fold higher for Nona Bokra and 6-fold higher for Pokkali compared with Taichung N1. Both the salt-induced endogenous ABA levels and a greater molecular response of root tissue to ABA were associated with the varietal differences in tolerance. PMID- 7870813 TI - Circadian oscillation of nitrate reductase activity in Gonyaulax polyedra is due to changes in cellular protein levels. AB - A circadian rhythm in the activity of nitrate reductase (NR; EC 1.6.6.1) isolated from the marine dinoflagellate Gonyaulax polyedra is shown to be attributable to the daily synthesis and destruction of the protein. The enzyme was purified in three steps: gel filtration on S-300 Sephacryl, an Affigel-Blue column, and a diethylaminoethyl ion-exchange column. Undenatured protein shows a molecular mass of about 310 kD; based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the enzyme appears to be composed of six possibly identical subunits. The amino acid composition of the G. polyedra NR is very similar to that reported for the NR of barley leaves, Chlorella vulgaris, and Ankistrodesmus braunii. The experiments reported indicate that the cellular expression of NR is under circadian control. In extracts of cells grown under either constant dim light or a light-dark cycle, the activity of NR exhibits a daily rhythm, peaking at midday phase, as does photosynthesis. Staining with affinity-purified polyclonal antibodies, raised in rabbits against purified NR, shows that the amount of protein changes by a factor of about 10, with the maximum occurring in midday phase. PMID- 7870814 TI - A cDNA from Medicago sativa encodes a protein homologous to small GTP-binding proteins. PMID- 7870815 TI - Sequence of a cDNA clone encoding a potato (Solanum tuberosum) tuber lipoxygenase. PMID- 7870816 TI - Nucleotide sequence of an operon in Nostoc sp. strain ATCC 29133 encoding four genes of the oxidative pentose phosphate cycle. PMID- 7870817 TI - A high mobility group protein cDNA clone from barley. PMID- 7870818 TI - Serine hydroxymethyltransferase from Solanum tuberosum. PMID- 7870819 TI - A cDNA encoding a PR-1-like protein in the model legume Medicago truncatula. PMID- 7870820 TI - Characterization of cDNAs encoding small GTP-binding proteins from maize. PMID- 7870821 TI - The gene structure of starch phosphorylase from sweet potato. PMID- 7870822 TI - A cDNA sequence encoding glutamine synthetase is preferentially expressed in nodules of Vigna aconitifolia. PMID- 7870823 TI - Nucleotide sequence of a wheat cDNA encoding protein disulfide isomerase. PMID- 7870824 TI - Sequences of three Arabidopsis general regulatory factor genes encoding GF14 (14 3-3) proteins. PMID- 7870825 TI - Genomic nucleotide sequence of an Arabidopsis thaliana gene encoding a cinnamyl alcohol dehydrogenase. PMID- 7870826 TI - An endomembrane-localized small heat-shock protein from Arabidopsis thaliana. PMID- 7870827 TI - Nucleotide sequence of a gene encoding a 58.5-kilodalton barley dehydrin that lacks a serine tract. PMID- 7870828 TI - A new methionine-rich seed storage protein from maize. PMID- 7870829 TI - Nucleotide sequence of a cDNA for the potato (Solanum tuberosum L.) chloroplast ribosomal protein S16. PMID- 7870830 TI - A cDNA encoding a metallothionein I-like protein from coffee leaves (Coffea arabica). PMID- 7870831 TI - Nucleotide sequence of a cDNA for 1-aminocyclopropane-1-carboxylate synthase from melon fruits. PMID- 7870832 TI - Nucleotide sequence of a cDNA encoding rice chloroplastic carbonic anhydrase. PMID- 7870833 TI - Molecular characterization of disease-resistance response gene DRR206-d from Pisum sativum (L.). PMID- 7870834 TI - Nucleotide sequence of a Lophopyrum elongatum mitochondrial proline tRNA gene. PMID- 7870835 TI - Nucleotide sequence of a cDNA clone encoding a thaumatin-like protein from Arabidopsis. PMID- 7870836 TI - Complete nucleotide sequence of the S1-RNase gene of Petunia hybrida. PMID- 7870837 TI - Isolation of a full-length cDNA encoding Zea mays gamma-tubulin. PMID- 7870838 TI - A cDNA clone encoding the 27-kilodalton subunits of glutathione S-transferase IV from Zea mays. PMID- 7870839 TI - Nucleotide sequence analysis of a cDNA encoding chloroplastic fructose-1,6 bisphosphatase from pea (Pisum sativum l.). PMID- 7870841 TI - The shikimate pathway as an entry to aromatic secondary metabolism. PMID- 7870842 TI - [On the symptomatological meaning of the others-intruding symptoms]. AB - There is a group of patients who insist as follows: "Someone comes into my room during my absence and removes, conceals or steals my belongings. In addition the intruder sometimes scatters about dirty things." "A young man living just across from my room is always observing me and criticizing my behavior." The others intruding symptoms like those above are frequently harbored by the female patients of paranoia and schizophrenia. However, these symptoms are rarely seen in male patients. My study shows that fourteen out of fifty-six female employees patients having the paranoic or schizophrenic symptoms had the so-called others intruding symptoms. At the time of visiting the psychiatric department of the center, the ages of the patients varied from 18 to 51 years old and five cases were in their thirties. Ten patients were single and two cases were divorced. Most of these patients were living alone. In some cases, the others-intruding symptoms faded away after the patients began living with their family members. In eight cases, there was a change of residence before the appearance of the symptoms. The patients have the following character traits: assertive, obstinate, unstable, unsociable and lacking adaptability. Although some patients showed mood fluctuations, they consistently displayed their delusion which distinguished them from maniac depressive patients. More than half of the patients showed neither the severe personality disorders nor rapid deterioration which are typically seen in the schizophrenic process. The patients of others-intruding symptoms have the same experience as those of mysophobia. The patients believe someone or something dirty invade their private space and deprive them of their cleanliness, freedom and security. In contrast, the patients of anthrpophobia and egorrhea feel that they are shunned by others because of something dirty which goes out of the patient's ego and threatens others. Usually the delusion of persecution accompanies the others-intruding symptoms; however the others-intruding patients exhibit no feelings of guilt. This is quite contrary to the symptoms of egorrhoea. The patients of these two types of symptoms are different in ages, character traits, duration of the symptoms, suicide rate, attitude towards therapy and therapists. We can postulate the following symptomatic spectrum: subclinical anthropophobia, anthropophobia, paranoia of delusion of egorrhoea, two types of schizophrenia paranoia of others-intruding delusion, mysophobia, subclinical mysophobia. PMID- 7870840 TI - Subcellular localization of the inducible Chlorella HUP1 monosaccharide-H+ symporter and cloning of a Co-induced galactose-H+ symporter. AB - The unicellular green alga Chlorella kessleri can induce monosaccharide-H+ symport catalyzing the energy-dependent transport of D-glucose (D-Glc) and several other pentoses and hexoses across the plasmalemma. The gene coding for the inducible HUP1 monosaccharide-H+ symporter has been cloned and the protein has been characterized previously. The data presented in this paper demonstrate that the presence of the HUP1 gene product alone is not sufficient to cover the broad substrate specificity of monosaccharide transport in induced Chlorella cells. Two other HUP genes are shown to be co-induced in Chlorella in response to D-Glc in the medium. The cloning of HUP2 and HUP3 cDNA and genomic sequences is described, both being very homologous to HUP1. Modification of the 5' untranslated sequences of full-length cDNA clones of HUP2 and HUP3 allowed the functional expression of both transporters in Schizosaccharomyces pombe. HUP2 was shown to be a galactose-H+ symporter, whereas the substrate specificity of the HUP3 gene product is very similar to that of the HUP1 protein. However, HUP3 does not seem to be induced to high levels in Glc-treated Chlorella cells. Results are also presented proving that the product of the HUP1 gene is localized in the plasmalemma of D-Glc-induced Chlorella cells and is absent in plasma membranes of noninduced cells. Incubation of thin sections of Chlorella cells with anti-HUP1 antibodies and a fluorescence-labeled, second antibody yielded a ring of fluorescence on the surface of Glc-induced Chlorella cells. PMID- 7870843 TI - [Psychophysiological and psychological consequences after surgical treatment of obstructive sleep apnea syndromes]. AB - The purpose of this study is to investigate the effects of surgical treatment of psychophysiological and psychological measurement of obstructive sleep apnea syndromes (OSAS) patients, and to clarify the interrelationships regarding an evaluation of its improvement. The subjects, 17 inpatients (mean age: 41.9 +/- 13.8 [17-61] 15 males, 2 females), were given the diagnosis of OSAS at the International Classification of Sleep Disorders. 4-5 days before (Pre-Treatment: PT), 5-22 days after (13.0 +/- 4.8 days, Post-Operation: PO) and 3-6 months after (4.2 +/- 1.0 months, Follow Up: FU) the surgery, the examinations were performed. Polysomnography (PSG) were recorded from 21:00 to 6:00. Following PSG, for the changes in daytime sleepiness, Multiple Sleep Latency Test (MSLT), Stanford Sleepiness Scale (SSS) and Spaceaeromedicine fatigue check list (SAM) were applied with the interval of 2 hours from 8:00 to 20:00. The psychological battery were performed at PT and FU, that consisted of Uchida-Kraepelin Test (U K), Wechsler Adult Intelligence Scale-Revised (WAIS-R), Benton Visual Retention Test (BVRT) and Minnesota Multiphasic Personality Inventory (MMPI). Surgical procedures were determined by means of radiological and endoscopic examinations. The results were as follows. A. Psychophysiological measurement (1) Apnea Index (AI) decreased at PO compared with PT. Further at FU. AI improved significantly compared with PT and PO [AI: 43.9 +/- 19.2-->20.5 +/- 16.5-->11.2 +/- 11.4]. And apnea duration shortened significantly at PO and FU. In addition, % time O2 saturation below 90% (SaO2 < or = 90%) decreased significantly at FU compared with PT. (2) With the improvement of respiratory disturbance, the sleep architecture of FU improved more than those of PO, such as increase of sleep efficiency, %stage 2 and %stage 3 + 4, decrease of No. of stage shift, %Wake and %stage 1. (3) Daily average of MSLT Scores at PO did not change compared with PT. But at FU, they improved significantly to normal range [6.7 +/- 3.0-->8.0 +/- 3.5 ->11.4 +/- 3.9 (min.)], whereas daily average of SSS and SAM improved significantly at both PO and FU compared with PT. B. Psychological measurement (1) Dysfunction of task performance improved at FU. Mean value in U-K (1st and 2nd half) and mean IQ (performance and total) in WAIS-R increased significantly at FU compared with PT. (2) Immediate visual memories in BVRT did not change within normal range. (3) MMPI profiles at PT didn't show any personality or mood characteristics.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7870844 TI - Effects of alprazolam on increases in hormonal and anxiety levels induced by meta chlorophenylpiperazine. AB - The effects of alprazolam, a triazolobenzodiazepine, on hormonal and behavioral responses induced by meta-chlorophenylpiperazine (MCPP), a serotonin receptor agonist, were investigated in 10 healthy men. Alprazolam (0.5 mg) or placebo was given 1 hour before MCPP (0.5 mg/kg) or placebo. Cortisol, prolactin, and growth hormone (GH) release, MCPP and alprazolam plasma levels, anxiety level, and panic symptoms were measured over 210 minutes. MCPP was found to increase cortisol, prolactin, GH, and anxiety levels. Alprazolam decreased cortisol and GH levels but had no effect on prolactin. When used in combination with MCPP, alprazolam blunted MCPP-induced cortisol and GH release, and it blocked the anxiogenic effects of MCPP. PMID- 7870845 TI - Noradrenergic and dopaminergic interrelation in schizophrenia. AB - Growth hormone (GH) and prolactin (PRL) responses to the acute administration of clonidine (150 micrograms) and apomorphine (0.5 mg) were investigated in parallel in 20 drug-free subchronic and chronic schizophrenic patients and in nine control subjects. Neither basal levels of the two hormones nor their mean responses to both stimuli differed significantly between the two groups. However, eight patients had blunted GH responses to clonidine and seven to apomorphine; only two patients showed blunted GH responses to both stimuli. The blunted GH response to apomorphine correlated with the chronicity of the disorder. A greater than normal GH response to clonidine stimulation was observed in paranoid patients. Significant correlations were observed between negative symptoms and GH responses to clonidine (negative), between negative symptoms and PRL responses to apomorphine (positive), and between positive symptoms and PRL responses to apomorphine (negative). PMID- 7870846 TI - IQ and brain size in schizophrenia. AB - In a previous study of normal control subjects, positive correlations were demonstrated between intelligence, as measured by the Wechsler Adult Intelligence Scale-Revised, and various measures of brain size, as assessed by magnetic resonance imaging (Andreasen et al., 1993). The goal of this study was to see if these findings generalized to schizophrenia. Corresponding analyses were performed in a group of DSM-III-R schizophrenic patients (50 men and 22 women) and compared with a subset of those normal control subjects (32 men and 27 women) who were equivalent to the patient group in their age and the educational and socioeconomic background of their families of origin. Full Scale IQ score was found to be uncorrelated with any of the regions of interest for the patient group as a whole. When subjects were divided by sex, the female patients were found to have a pattern of correlations similar to that of normal control subjects, while no such relationship was apparent among the male patients. These differences did not appear to be attributable to variability in symptom severity. Thus, there appear to be gender-related differences in brain structure/function relationships in schizophrenic patients versus normal control subjects. PMID- 7870847 TI - Depressive symptoms among Japanese and American adolescents. AB - An epidemiologic study of depressive symptoms was conducted with self administered questionnaires among 8th grade students (12-15 years of age) in Japan (n = 570) and the United States (n = 115 Anglos, n = 180 Hispanics). The Todai Health Index-Depression Scale (THI-D), which had been developed in Japan, was used in the study after translation from Japanese to English for the U.S. subjects. The THI-D mean score for Japanese boys was significantly higher than that for Hispanic boys. Also, a gender difference was found across the ethnic groups, in which girls expressed depressive feelings more than boys. PMID- 7870848 TI - Responses to a self-administered depression scale among younger adolescents in Japan. AB - Response patterns on the Center for Epidemiologic Studies Depression Scale (CES D) items among Japanese adolescents were compared with those of their U.S. counterparts. The data were obtained from approximately 1,500 junior high school students, aged 12-15 years. Japanese responses to positively worded items markedly differed from those of American adolescents, whereas responses to negatively worded items were comparable in the two groups. This resulted in poor psychometric properties for the CES-D and spurious higher positive subscale and whole scale scores among the Japanese sample. It is possible that Japanese respondents tend to suppress positive affect expression and, thus, the positively worded questioning is presumably inappropriate for Japanese samples. PMID- 7870849 TI - Participation in and outcome of treatment for major depression among low income Asian-Americans. AB - This study examined the relationship of four aspects of psychiatric treatment (use of medication, client-therapist ethnic match, treatment in an Asian-specific clinic, and professional therapist) to participation in treatment and outcome of treatment in low income Asian-American clients (n = 273) of the Los Angeles County mental health system who were diagnosed with major depression. Based on cultural responsiveness theory, the study tested the hypothesis that use of medication in treatment would have the greatest effect on participation and outcome followed, in order, by client-therapist ethnic match, treatment in an Asian-specific clinic, and treatment by a professional therapist. The hypotheses were largely supported: treatment with medication had a significant relationship to total number of treatment sessions (participation) and improvement in the admission-discharge Global Assessment Scale (GAS) score (outcome). Treatment by a therapist of the same ethnicity as the client and treatment in an agency designated to provide services to Asian clients both had significant relationships to the number of treatment sessions but not to GAS score improvement. Four covariates included in the analysis and treatment by a professional therapist had no relationship to either of the dependent variables. PMID- 7870850 TI - "Normal" control subjects are hard to find: a model for centralized recruitment. AB - A central program for recruiting "normal" control subjects is examined by considering the yield of subjects who meet criteria for "healthy" as defined by their personal and family histories of mental disorders. Of the 267 applicants, 30.3% have no lifetime diagnoses, 41.2% are currently healthy with a history of mental illness, and 27.7% are currently mentally ill. Only 16.1% met Research Diagnostic Criteria for "never mentally ill" and reported no family history of mental disorders. Benefits of a central recruitment program for studies of mental disorders include increased information on a large subject pool and decreased volunteer bias. PMID- 7870851 TI - Change in folate status with antidepressant treatment. AB - Ninety-nine consecutive unmedicated outpatients with a major depressive illness had blood drawn for measurement of serum folate (SF), red cell folate (RCF), and vitamin B12 within 24 hours of completion of ratings of severity of depression at the beginning and ending of a 5-week trial of desmethylimipramine (mean dose = 149.2 mg/day, range = 75-225 mg). As compared with nonresponders, responders had a significantly higher mean SF at baseline (nonresponders = 13.8 nmol/l; responders = 17.7 nmol/l) and RCF showed a significant inverse correlation with severity of depression and a significant positive correlation with age of onset of illness. At week 5, change in severity of depression was significantly correlated with change in RCF, and significantly more responders than nonresponders had an increase in RCF. The possible role of folate status in the regulation of mood and response to treatment is discussed. PMID- 7870852 TI - Preliminary report: cerebral blood flow abnormalities in older schizophrenic patients. AB - We compared global and regional cerebral blood flow in 11 schizophrenic patients and 11 normal comparison subjects, all over the age of 45 years. The schizophrenic patients had lower global cortical uptake than the control subjects. Among the individual regions of interest, the schizophrenic patients had significant decrements in the left posterior frontal region and in the bilateral inferior temporal regions. The uptake did not correlate with age of onset or duration of schizophrenia, current daily neuroleptic dose, severity of psychopathology, or global cognitive impairment. PMID- 7870853 TI - Prefrontal dysfunction in young acute neuroleptic-naive schizophrenic patients: a resting and activation SPECT study. AB - Regional cerebral blood flow (rCBF) was measured with single photon emission computed tomography (SPECT) in six neuroleptic-naive, young, acute schizophrenic patients and six normal control subjects. We evaluated rCBF changes in prefrontal areas at rest and during a prefrontal activation task, the Wisconsin Card Sorting Test (WCST). Schizophrenic patients had significantly higher prefrontal blood flow than did control subjects during the resting conditions. During activation, the control group showed significant increases in prefrontal blood flow, whereas the schizophrenic group did not. These results suggest that at rest there is no evidence of hypofrontality, whereas hyperfrontality seems to be the most frequent pattern in our selected sample of young acute neuroleptic-naive schizophrenic patients. Furthermore, schizophrenic patients seem to be unable to increase prefrontal blood flow under conditions that challenge the prefrontal cortex. PMID- 7870854 TI - Assessment of cerebral perfusion using quantitative EEG cordance. AB - Brain electrical activity is related to cerebral perfusion. The nature of this relationship is unclear, however, and surface-recorded activity has not been a reliable indicator of brain perfusion. We studied 27 subjects, all of whom were examined with single photon emission tomography (SPECT) and quantitative electroencephalography (QEEG), to assess associations between QEEG cordance and relative brain perfusion. Cordance has two indicator states: concordance, which may indicate high perfusion; and discordance, which may indicate low perfusion. We used multiple linear regression to assess the association between cordance and SPECT values, and found that cordance values were strongly associated with tissue perfusion. Concordance in the alpha band was associated both with mean tissue perfusion and the volume of normally perfused tissue, and it had a stronger association with perfusion than any other QEEG variable. Discordance in the beta 1 band was associated with mean perfusion, and it had a stronger association than did relative but not absolute power. These data suggest that cordance may be useful for the noninvasive assessment of brain perfusion. PMID- 7870855 TI - P300 asymmetries in schizophrenia revisited with reference-independent methods. AB - Evidence of hemispheric asymmetries in schizophrenia has been reported from different research areas. Asymmetries in evoked potential P300 topography are still controversial because of inconsistent findings. In the present study, previous results of abnormal lateralization of P300 were replicated in stabilized residual schizophrenic patients. Auditory P300 was recorded during an oddball task in which subjects detected rare target stimuli. Schizophrenic patients had the P300 peak shifted to the right hemisphere and differed significantly from age and sex-matched normal control subjects who had left-lateralized P300 peaks. A comparison of different methods of assessment and analysis of the topographical features of the P300 electric fields showed that the extraction of reference independent descriptors of P300 topography is a reliable and sensitive method for statistical handling of the maps. The results suggest left hemispheric dysfunction during cognitive tasks in a subgroup of schizophrenic patients. Inconsistencies between previous studies are likely to be due to heterogeneous patient groups, which may have included patients in an acute schizophrenic episode or patients in clinical remission. Investigation of the clinical meaning of P300 alterations requires careful psychopathological definition of the patient groups. PMID- 7870856 TI - Relative accuracy and reproducibility of regional MRI brain volumes for point counting methods. AB - Volumetric magnetic resonance imaging (MRI) methods for the measurement of various neuroanatomical regions are of great interest in studies of neuropsychiatric disorders. Both manual and semiautomated methods have been developed. Manual methods include tracing and point counting. Point counting methods are widely used in post-mortem and microscopy studies. Point counting has been well validated for these purposes. In this article, we report in a series of separate studies the accuracy and reproducibility of point-counting methods. Absolute accuracy was evaluated with a spherical phantom. Accuracy and time efficiency were subsequently assessed with an anatomically realistic phantom and various size grids. The point-counting method was also compared to a tracing method. Finally, the reproducibility of the point-counting method for the caudate and putamen was evaluated on four subjects in a test-retest experiment. These studies provide an estimate of the accuracy and time efficiency of point-counting methods. The test-retest reliability was also high for both caudate and putamen. Findings suggest that point counting is a reliable and efficient method for estimating volumes. PMID- 7870857 TI - Stuttering, language, and cognition: a review and a model of stuttering as suprasegmental sentence plan alignment (SPA). AB - Extant models of stuttering do not account for the emergence of stuttering at the onset of productive language use; the greater incidence of stuttering during spontaneous speech, on complex sentences, and at sentence-initial positions; the greater incidence of stuttering in bilinguals' 2nd language; the apparent deficiency of stutterers in expressive and receptive language skills; the prevalence of spontaneous recovery from stuttering; and the lack of chronic physiological or articulatory deficits in stuttering children's fluent speech. The author presents a model of stuttering as points of suprasegmental sentence plan alignment (SPA). Such alignment processes occur when, due to on-line sentence production processes, SPAs adopted prior to utterance initiation need to be aligned with revised SPAs. This model parsimoniously accounts for the findings reviewed in the article. PMID- 7870858 TI - Gender and the effectiveness of leaders: a meta-analysis. AB - This article presents a synthesis of research on the relative effectiveness of women and men who occupy leadership and managerial roles. Aggregated over the organizational and laboratory experimental studies in the sample, male and female leaders were equally effective. However, consistent with the assumption that the congruence of leadership roles with leaders' gender enhances effectiveness, men were more effective than women in roles that were defined in more masculine terms, and women were more effective than men in roles that were defined in less masculine terms. Also, men were more effective than women to the extent that leader and subordinate roles were male-dominated numerically. These and other findings are discussed from the perspective of social-role theory of sex differences in social behavior as well as from alternative perspectives. PMID- 7870859 TI - Sex differences in attitudes toward homosexuality: a comment on Oliver and Hyde (1993) AB - In a recent article, M. B. Oliver and J. S. Hyde (1993) reported the results of a set of meta-analyses of gender differences on a number of sexuality-related variables, including attitudes toward homosexuality. The small number of studies on this topic included in the review suggested that Oliver and Hyde's literature search strategy overlooked a number of studies. This article reports the results of a new meta-analysis using an expanded search strategy. In contrast to Oliver and Hyde's results, it was found that men held more negative attitudes toward homosexuality and, to a lesser extent, the civil rights of lesbians and gay men than did women. Effect sizes were moderated by subject population, with general adult samples showing no sex difference and other samples showing larger effect sizes. Effect sizes also varied as a function of the sex of the person rated, with larger sex differences for gay men than for lesbians. The implications of the results for the process of literature reviewing and for gender-based explanations of antigay prejudice are discussed. PMID- 7870860 TI - Meta-analysis of screening and diagnostic tests. AB - Screening and diagnostic tests are common in the fields of psychology, medicine, and education. Often there are several competing tests, and decisions must be made about the relative accuracy of those tests. This article describes a general measure that can be used for both continuous and dichotomous outcome measures. It is the standardized distance between the means of the 2 populations. For continuous measures, it is the effect size measure. For dichotomous measures, it is proportional to the logarithm of the odds of the sensitivity plus the logarithm of the odds of the specificity. The measure is easily computed for both kinds of outcomes. Properties of this measure are discussed, and examples are given. Ths use of this measure to compare the average performance of different tests is described. PMID- 7870861 TI - The correspondence bias. AB - The correspondence bias is the tendency to draw inferences about a person's unique and enduring dispositions from behaviors that can be entirely explained by the situations in which they occur. Although this tendency is one of the most fundamental phenomena in social psychology, its causes and consequences remain poorly understood. This article sketches an intellectual history of the correspondence bias as an evolving problem in social psychology, describes 4 mechanisms (lack of awareness, unrealistic expectations, inflated categorizations, and incomplete corrections) that produce distinct forms of correspondence bias, and discusses how the consequences of correspondence-biased inferences may perpetuate such inferences. PMID- 7870862 TI - Psychological correlates of obesity: moving to the next research generation. AB - Studies comparing obese and nonobese persons have generally failed to find differences in global aspects of psychological functioning (e.g., depression, anxiety). The resulting conclusion, that obesity does not carry risk for psychological problems, is inimical to clinical impression, reports from overweight individuals, and a consistent literature showing strong cultural bias and negative attitudes toward obese persons. The often-cited notion that obesity has no psychological consequences may be an inevitable byproduct of the manner in which the first generation of studies in the field has been conducted. The authors propose a second generation of studies that begins with a risk factor model to identify the individuals who will suffer from their obesity and the areas of functioning most affected. Recommendations are also made for a third generation of studies that will establish causal pathways linking obesity to specific areas of distress. PMID- 7870863 TI - Mood and judgment: the affect infusion model (AIM). AB - Evidence for the role of affective states in social judgments is reviewed, and a new integrative theory, the affect infusion model (AIM), is proposed as a comprehensive explanation of these effects. The AIM, based on a multiprocess approach to social judgments, identifies 4 alternative judgmental strategies: (a) direct access, (b) motivated, (c) heuristic, and (d) substantive processing. The model predicts that the degree of affect infusion into judgments varies along a processing continuum, such that judgments requiring heuristic or substantive processing are more likely to be infused by affect than are direct access or motivated judgments. The role of target, judge, and situational variables in recruiting high- or low-infusion judgmental strategies is considered, and empirical support for the model is reviewed. The relationship between the AIM and other affect-cognition theories is discussed, and implications for future research are outlined. PMID- 7870864 TI - Reviewing theories of adolescent substance use: organizing pieces in the puzzle. AB - This article reviews 14 multivariate theories of experimental substance use (e.g., alcohol and marijuana use) among adolescents, including those theories that emphasize (a) substance-specific cognitions, (b) social learning processes, (c) commitment to conventional values and attachment to families, and (d) intrapersonal processes. Important similarities and differences among these theories are addressed, as are the conceptual boundaries of each theory. In an attempt to integrate existing theories, a framework is proposed that organizes their central constructs into 3 distinct types of influence (viz., social, attitudinal, and intrapersonal) and 3 distinct levels of influence (viz., proximal, distal, and ultimate). Implications for future theory development are discussed. PMID- 7870865 TI - Latent inhibition in humans: data, theory, and implications for schizophrenia. AB - Learning about the consequences of a stimulus is retarded if that stimulus has been experienced without reinforcement. A literature review of this latent inhibition (LI) effect indicates that LI is similar in human and other species, although in adult humans it often requires a masking or distracter task. The discrepancy in conditions for producing LI can be accounted for by developmental differences in the automatic processing of unattended stimuli. In adults, automatic processes are subject to a controlled information-processing override. Masking prevents controlled processing of the preexposed stimuli so that they remain unattended. The role of masking in attenuating LI in schizotypal/schizophrenic groups is assessed. It is proposed that schizophrenia is related to an inability to use occasion-setting properties of context or to switch from controlled to automatic processing of inconsequential events. PMID- 7870866 TI - Differential sensitivity to midazolam discriminative-stimulus effects following self-administered versus response-independent midazolam. AB - Interactions between the discriminative and reinforcing effects of midazolam were studied in two baboons trained to discriminate midazolam (0.32 mg/kg, IV) from saline. The midazolam generalization gradient determined after the baboons were permitted to self-administer midazolam (IV) was shifted to the left of that determined before self-administration. In contrast, the midazolam generalization gradient determined after the same doses of midazolam were delivered response independently, but in the same order and with the same temporal pattern as during self-administration, was shifted to the right of that determined just before the response-independent phase. These data suggest that sensitivity to the discriminative-stimulus effects of a drug can be modulated by behavioral experience with that drug. PMID- 7870867 TI - Effect of acute and chronic diisopropylfluorophosphate and atropine administration on somatostatin binding in the rat frontoparietal cortex and hippocampus. AB - The acute and chronic administration of diisopropylfluorophosphate (DFP), an inhibitor of acetylcholinesterase (AChE), and of atropine, a blocker of muscarinic cholinergic receptors, did not affect somatostatin-like immunoreactivity (SLI) content in the frontoparietal cortex and hippocampus of rats. Acute and chronic DFP administration increased the number of specific 125I Tyr11-somatostatin (125I-Tyr11-SS) receptors in synaptosomes from the frontoparietal cortex but not in those from the hippocampus and did not change the affinity constant. This increase in 125I-Tyr11-SS binding was not due to a direct effect of DFP on somatostatin (SS) receptors since no rise of binding was produced by high concentrations of DFP (10(-5) M) when added in vitro. The increase could be blocked by pretreatment with atropine. The acute administration of atropine alone had no observable effect on the number of SS receptors. However, repeated atropine administration produced a significant decrease in the 125I-Tyr11-SS binding in synaptosomes from the frontoparietal cortex but not in those from the hippocampus although the affinity constant was unchanged. The results suggest that interactions between somatostatinergic and cholinergic receptors may be important in the rat frontoparietal cortex. PMID- 7870868 TI - Effects of concurrent subchronic treatments with desmethylimipramine and propranolol on beta-adrenergic and serotonin2 receptors in rat brain. AB - The effects of seven consecutive daily injections of desmethylimipramine (DMI 20 mg/kg) and propranolol (PRO 10 mg/kg) on 3H-dihydroalprenolol (3H-DHA) and 3H ketanserin (3H-KET) binding in rat brain were examined. Analyses of saturation binding data using the iterative, nonlinear curve-fitting program LIGAND revealed that PRO increased, while DMI reduced, 3H-DHA binding site density in cerebral cortex without altering receptor affinity, as previously reported. DMI reduced 3H KET binding site density without changing affinity, and PRO produced the same effect. In cerebral cortex and probably in hippocampus and striatum, DMI and PRO administered together increased the density of 3H-DHA binding sites (beta adrenergic receptors) and reduced their affinity. This combination of drugs reduced the density of 3H-KET binding sites (5-HT2 receptors) in cerebral cortex, but did not change their affinity. These findings indicate a need for additional studies on the interactions of DMI and PRO and related drugs because of implications for the treatment of depressed patients with cardiovascular disorders. PMID- 7870869 TI - In a drug discrimination procedure isolation-reared rats generalize to lower doses of cocaine and amphetamine than rats reared in an enriched environment. AB - Rats with different behavioral histories, defined by rearing and housing in either an enriched condition (EC) or an isolation condition (IC), were trained in a two-lever operant procedure to discriminate 5.0 mg/kg cocaine from saline. In cocaine dose-generalization tests, the IC rats exhibited an ED50 (1.01 mg/kg) significantly lower than the EC rats (ED50: 1.55 mg/kg). The cocaine-appropriate responding was emitted when the rats were treated with d-amphetamine, and for the d-amphetamine test doses the ED50 (0.19 mg/kg) was again significantly lower for the IC rats compared to the ECs (ED50: 0.33 mg/kg). These data suggest that IC rats are more sensitive to the stimulus properties of indirect dopaminergic agonists than EC rats and highlight the importance of environmental variables in governing an organism's response to the stimulus properties of abused drugs. PMID- 7870870 TI - Clozapine's functional mesolimbic selectivity is not duplicated by the addition of anticholinergic action to haloperidol: a brain stimulation study in the rat. AB - This study examined whether the anticholinergic potency of the clinically superior antipsychotic drug clozapine contributes to clozapine's anatomically selective functional inhibition of the mesolimbic dopamine (DA) system, using an electrical brain-stimulation reward (BSR) paradigm in rats that has been previously shown to be highly sensitive to clozapine's mesolimbic functional selectivity. Rats were chronically administered saline, clozapine, haloperidol, or haloperidol plus the anticholinergic compound trihexyphenidyl, and threshold sensitivity of the mesolimbic and nigrostriatal DA systems was assessed using the BSR paradigm, to infer degree of functional DA blockade produced by the chronic drug regimens. Chronic saline produced no change in either DA system. Congruent with previous findings, chronic clozapine powerfully inhibited the mesolimbic DA system but spared the nigrostriatal DA system. Also congruent with previous findings, chronic haloperidol powerfully inhibited both DA systems. Compared to chronic haloperidol alone, chronic haloperidol plus chronic trihexyphenidyl exerted diminished anti-DA action in both the mesolimbic and nigrostriatal DA systems. These results suggest that clozapine's anticholinergic potency is not an adequate explanation for its functional mesolimbic selectivity. PMID- 7870871 TI - Development of both conditioning and sensitization of the behavioral activating effects of amphetamine is blocked by the non-competitive NMDA receptor antagonist, MK-801. AB - The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, has been shown to block the development of sensitization of the behavioral activating effects of amphetamine. Three experiments were designed to determine in rats whether MK-801 had its effects through interference with long-term changes underlying sensitization, per se, or through interference with the development of conditioning of the drug effect to the environment where the drug was given. In experiment 1, conditioning was promoted by explicitly pairing amphetamine (1.5 mg/kg, IP) with the testing environment. In experiment 2, a random-pairing procedure was used to eliminate the possibility of association between the drug and a specific context. Experiment 3 was carried out to assess the duration of the blockade of sensitization by MK-801. The effect of MK-801 (0.25 mg/kg, IP) during amphetamine pre-exposure was studied in tests for conditioning (following saline injections, experiment 1) and in tests for sensitization (following 0.75 mg/kg amphetamine, experiments 1, 2 and 3). It was found in experiment 1 that MK 801 given with amphetamine during the amphetamine pre-exposure phase blocked the development of both conditioning activity and environment-specific sensitization to amphetamine. The results of experiment 2, showing that sensitization to amphetamine was blocked by MK-801 even when conditioning was prevented, suggest that the two effects of MK-801 are independent, and may implicate different sites of action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870872 TI - Neuropharmacology of a new potential anxiolytic compound, F 2692, 1-(3' trifluoromethyl phenyl) 1,4-dihydro 3-amino 4-oxo 6-methyl pyridazine. 1. Acute and in vitro effects. AB - F 2692 [1-(3'-trifluoromethyl phenyl) 1,4-dihydro 3-amino 4-oxo 6-methyl pyridazine] exhibited dose-dependent "anxiolytic" properties in the elevated plus maze and the punished drinking tests in rats. It was also active in the two compartment test in mice. The "anxiolytic" effects were antagonised by the benzodiazepine antagonists, flumazenil and ZK 93426. The compound exhibited anticonvulsant, sedative, myorelaxant and amnesic effects at doses 3-30 times higher than those required for "anxiolytic" activity. F 2692 has a very low affinity for benzodiazepine binding sites in vitro and in vivo (about 1000 and 160 fold lower than diazepam respectively). In addition it displayed no affinity for GABAA, alpha 2-adrenergic, 5-HT1A or 5-HT2 receptors. These data suggest that F 2692 may be a potential anxiolytic compound with an unusual mechanism of action. PMID- 7870873 TI - Effect of some stereoisomeric tricyclic antidepressants on 45Ca uptake in synaptosomes from rat hippocampus. AB - The present study has examined the inhibition of synaptosomal 45calcium uptake by trimipramine, oxaprotiline and doxepin, and their stereoisomers, in synaptosomes from the rat hippocampus. No significant difference in potency could be established for inhibition of net depolarization-induced 45calcium uptake for any pair of antipodes, and the IC50 values for calcium channel blockade were in the vicinity of 30 microM for this group of compounds. Trimipramine, doxepin and oxaprotiline also inhibited the 45calcium uptake mediated by Na(+)-Ca2+ exchange, with IC50 values of 71 microM, 110 microM, and 100 microM, respectively. The similar potency of doxepin isomers for inhibition of voltage-dependent calcium channels is in harmony with their reported similar potency in the clinic. A slight difference in potency is reported between the isomers of oxaprotiline in the behavioral despair test in rats, and the dextrorotatory isomer of trimipramine is reported to be a much more potent antidepressant than the levorotatory isomer: these order of potencies do not correspond perfectly with the similar potency of the antipodes against voltage-dependent calcium channels. The present study of stereoisomeric tricyclic antidepressants therefore fails to provide unequivocal support for the hypothesis that calcium channel blockade by tricyclic antidepressants is involved in their therapeutic effect. PMID- 7870874 TI - Effects of repeated mild stress and two antidepressant treatments on the behavioral response to 5HT1C receptor activation in rats. AB - This study investigated the possible involvement of 5HT1C receptors in the development of depressive states and in the mode of action of antidepressants. The effects of repeated unpredictable mild stress (a regimen known to induce an anhedonic state in the rat) and of chronic administration of either of two recognized antidepressant treatments (sleep deprivation or inhibition of monoamine oxidase type A) in rats were studied on a 5HT1C receptor initiated response, i.e. mCPP-induced penile erection. A 3-week period of repeated, but unpredictable exposure to mild stressors induced a shift to the left of the dose response curve for mCPP-induced penile erection. In contrast, 72-h REM sleep deprivation resulted in a shift to the right of the mCPP dose-response curve and 10-day administration of the monoamine oxidase type A inhibitor moclobemide (20 mg/kg IP bid) also resulted in a decreased number of mCPP-induced penile erections. These findings support the hypothesis that neuronal activities initiated via 5HT1C receptor stimulation may play a role in the pathophysiology and treatment of depression. PMID- 7870875 TI - Subcortical dopamine and serotonin turnover during acute and subchronic administration of typical and atypical neuroleptics. AB - The effects of acute (1 day) and subchronic (28 days) treatment with three atypical antipsychotic drugs [clozapine, (+/-)-sulpiride and (-)-3-PPP] on dopamine and serotonin turnover in both the nucleus accumbens (NA) and corpus striatum (CS) of rodents was compared to haloperidol and saline treatment. The equivalent doses of all drugs were determined based upon their ability to compete in vivo for 3H-spiperone binding in the NA and CS. All three atypical drugs, compared to haloperidol, produced preferential elevations of dopamine turnover in the NA. Further, the development of tolerance of this effect was more apparent for the three atypical drugs than for haloperidol. Surprisingly, all three atypical drugs, but not haloperidol, produced changes in serotonin turnover, despite the fact that (+/-)-sulpiride and (-)-3-PPP have no known direct effects on brain serotonin systems. All three atypical drugs produced acute increases in serotonin turnover in both the NA and CS, followed by later diseases. PMID- 7870876 TI - Subsensitivity to rewarding and locomotor stimulant effects of a dopamine agonist following chronic mild stress. AB - Chronic exposure to very mild unpredictable stress has previously been found to reduce or abolish the acquisition of place preference conditioning. In the present study, chronic mild stress was found to abolish the acquisition of preferences for a distinctive environment paired with systemic administration of amphetamine (0.5 mg/kg) or quinpirole (100-400 micrograms/kg) or with quinpirole (0.75 micrograms) administered bilaterally within the nucleus accumbens. The locomotor stimulant effects of quinpirole (100-400 micrograms/kg) were also attenuated in stressed animals. The result suggest that decreased sensitivity to reward following chronic mild stress results from a decreased sensitivity of dopamine D2 receptors within the nucleus accumbens. PMID- 7870877 TI - Behavioural sensitization to a dopamine agonist is associated with reversal of stress-induced anhedonia. AB - Chronic exposure to very mild unpredictable stress (CMS) has previously been found to reduce the consumption of palatable sweet solutions and to impair place preference conditioning; evidence has been presented that these effects may reflect a dysfunction of the mesolimbic dopamine system. In the present study, rats were subjected to CMS for a total of 9 weeks. CMS reduced the consumption of a 1% sucrose solution. During weeks 6 and 7, animals received quinpirole (0-400 micrograms/kg) twice weekly. Both CMS-treated animals and controls showed sensitization to the locomotor stimulant effects of quinpirole. Subsequently, a sustained recovery of sucrose drinking was observed in quinpirole-treated stressed animals. During week 8, all animals received a single pair of place preference conditioning trials, in which quinpirole (200 micrograms/kg) was administered in a distinctive environment, and vehicle in a different environment. Non-stressed animals showed an increase in preference for the environment associated with quinpirole, as did stressed animals that had been sensitized to quinpirole, this effect was absent in untreated stressed animals. Finally, in week 9, acute administration of raclopride (150 micrograms/kg) was found to reverse the recovery of sucrose drinking in quinpirole-treated stressed animals, suggesting that these effects are mediated by an increase in dopamine function. PMID- 7870878 TI - The NMDA positive modulator D-cycloserine potentiates the neuroleptic activity of D1 and D2 dopamine receptor blockers in the rat. AB - According to the view that N-methyl-D-aspartate (NMDA) agonists could be seen as putative therapeutic agents in schizophrenia, the present study was aimed at investigating whether the NMDA positive modulator D-cycloserine (DCS) could show neuroleptic activity. When given alone, DCS (1.5, 3, 6, 12 mg/kg) failed to affect the stereotyped behavior induced by 0.5 mg/kg SC apomorphine, a test routinely used to detect neuroleptic activity. Nevertheless, the administration of different doses of DCS (1.5, 3, 6 mg/kg) in combination with the D1 dopamine receptor blocker SCH 23390 or the D2 antagonist YM 09151-2, both given in doses which by themselves were ineffective in blocking apomorphine elicited behavior, induced a dose- dependent neuroleptic effect. Furthermore the positive NMDA modulator allowed (-)-sulpiride, which given alone never antagonized the apomorphine-induced stereotypy, to exhibit a full neuroleptic activity. The lower dose of DCS effective in potentiating antipsychotic effect of dopaminergic blockers also counteracted the behavioral response (hypermotility) induced by the NMDA negative modulator MK-801 (0.25 mg/kg), thus indicating the specificity of DCS effect. The results strengthen the view that drugs which increase NMDA receptor function could be a useful supplement in the therapy of psychotic disorders. PMID- 7870879 TI - Caffeine and nicotine improve visual tracking by rats: a comparison with amphetamine, cocaine and apomorphine. AB - Psychomotor stimulant drugs such as caffeine, nicotine, amphetamine and cocaine, have been shown to improve vigilance in man under conditions of fatigue. Nicotine has also been shown to improve performance in some cognitive tests in patients with Alzheimer's disease. In rodents these drugs increase activity which may confound "performance enhancing effects" in rodent models. However, improvements have been found in a number of tests that do not seem to be directly dependent upon an enhancement of locomotor activation. In one example, Evenden and Robbins (1985) reported consistent improvements in a visual tracking test following amphetamine. The present study was undertaken to determine whether these performance enhancing effects of amphetamine could also be obtained with cocaine and apomorphine, which both have psychomotor stimulant effects through their actions as, respectively, indirect and direct dopamine agonists, and by caffeine and nicotine, which do not have a direct dopaminergic mechanism of action. The results of the study indicate that all five drugs improved tracking performance at one or more doses. The most consistent effects were obtained with amphetamine which, like cocaine and nicotine, improved tracking at a dose which did not produce other changes in behaviour. Taking into account previous studies (Evenden and Robbins 1983, 1985), these results were interpreted as indicating that psychomotor stimulant drugs produce a general activation of behaviour. At all but the highest doses of such drugs, the form of behaviour that is observed depends upon the environment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870880 TI - Neuroendocrine profile of SDZ HDC-912 and OPC-4392, two new atypical antipsychotic drugs, in schizophrenic patients. AB - The aim of this study was to evaluate the effect on the activity of the hypothalamic-pituitary dopaminergic system of two new atypical antipsychotic drugs: the ergoline derivative SDZ HDC-912, which is a dopamine (DA) D2 receptor partial agonist; and the quinolinone derivative OPC-4392, which acts as an agonist at presynaptic DA autoreceptors and as an antagonist at post-synaptic D2 receptors. The effects of both compounds were compared to the effects of the benzamide derivative amisulpride. Prolactin (PRL) and growth hormone (GH) levels before and after challenge with apomorphine (Apo), a dopaminergic agonist, were determined after at least 2 weeks washout and again after 1 month of treatment in DSM-III-R schizophrenic inpatients. SDZ HDC-912 significantly decreased Apo induced PRL inhibition, and tended to decrease PRL secretion and Apo-induced GH stimulation. OPC-4392 induced a significant decrease in baseline PRL and in Apo induced PRL suppression, and a non-significant decrease in Apo-induced GH stimulation. The neuroendocrine profiles of these two compounds agree with their dopaminergic properties; however, the decrease in PRL basal level differentiates the two drugs from neuroleptic agents. PMID- 7870881 TI - A comparison of the amnesic effects of lorazepam in alcoholics and non alcoholics. AB - The transient amnesia produced by lorazepam has been suggested to have much in common with the permanent amnesia associated with organic brain damage. The present study examined the amnesia associated with chronic alcoholism and acute lorazepam administration and hypothesised that because alcoholics have prior impairment, their response to lorazepam induced amnesia would differ from that of non-alcoholics. Memory functioning was tested in 20 chronic alcoholics and 20 non alcoholic controls both before and after administration of either 2 mg lorazepam or a placebo. It was found that, although there were some discrepancies on some of the memory tests, both long term alcohol abuse and acute lorazepam administration impaired visual and verbal episodic memory but did not impair semantic or short-term memory (STM). PMID- 7870882 TI - Nicotine blocks latent inhibition in rats: evidence for a critical role of increased functional activity of dopamine in the mesolimbic system at conditioning rather than pre-exposure. AB - Latent inhibition (LI) is a cognitive process whereby repeated exposure of a stimulus without consequence impedes the formation of subsequent associations with that stimulus. A number of studies in the rat have reported that LI is impaired by moderate systemic doses of amphetamine, an effect believed to be mediated via dopamine (DA) release in the nucleus accumbens. We and others have reported that nicotine has a selective effect in releasing DA in the accumbens rather than the caudate nucleus. We have therefore examined the ability of nicotine to disrupt LI, using a conditioned emotional response paradigm. Pre exposure of a tone stimulus impaired subsequent conditioning between that stimulus and mild footshock, as indexed by suppression of licking by the tone subsequently presented alone. This LI effect was prevented, by an effect confined to the pre-exposed group, by doses of 0.4 or 0.6 mg/kg nicotine SC, which are accumbens selective, given before pre-exposure and before conditioning. The effect of nicotine in disrupting LI was prevented by prior administration of haloperidol at a dose (0.5 mg/kg) reported to reverse the disruptive effect of amphetamine on LI. Although the amphetamine effect requires two administrations, the effect of two administrations of nicotine was reproduced by a single dose of nicotine given before conditioning, but not by a single dose before pre-exposure. The results are discussed in relation to studies in human control and schizophrenic subjects, which suggest that increased DA activity in humans is also associated with impaired LI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870883 TI - Neuropharmacology of a new potential anxiolytic compound, F 2692, 1-(3' trifluoromethyl phenyl) 1, 4-dihydro 3-amino 4-oxo 6-methyl pyridazine. 2. Evaluation of its tolerance and dependence producing potential and of its effects on benzodiazepine withdrawal in the elevated plus-maze test in rats. AB - After 21 days administration, diazepam (0.3-3 mg/kg/day) exhibited, 30 min after the last injection, tolerance to the sedative effect and "anxiolytic" activity as recorded in the elevated plus-maze test in rats. A dose-dependent increase of "anxiety" was also observed 24 h after withdrawal from 21 or 90 days of diazepam treatment. In contrast, under the same experimental conditions, F 2692 [1-(3' trifluoromethyl phenyl) 1,4-dihydro 3-amino 4-oxo 6-methyl pyridazine] (3-30 mg/kg/day) exhibited no tolerance to either the sedative effect or the "anxiolytic" activity and showed no "anxiogenic rebound" response after withdrawal. Chronic diazepam pretreatment for 21 days modified neither the sedative effect nor the dose-dependent "anxiolytic" effect of F 2692. Furthermore, F 2692 could reverse the anxiogenic response after withdrawal from 21 days administration of diazepam. Finally, administration of diazepam for 3 weeks followed by a daily administration of F 2692 for a week induced no increase of "anxiety" 24 h after withdrawal. PMID- 7870884 TI - Bombesin-induced anorexia requires central bombesin receptor activation: independence from interaction with central catecholaminergic systems. AB - Intraperitoneal (IP) administration of bombesin (BBS; 2.5-20 micrograms/kg) induced a dose-dependent inhibition of food intake. The effect was decreased by intraventricular (ICV) administration of bombesin receptor antagonist [Leu14-psi (CH2NH)-Leu13] (3 micrograms/rat) but not by the D1 antagonist SCH 23390, the D2 antagonists sulpiride and pimozide, the dopamine antagonist cis-flupentixol, adrenoceptor blockers phenoxybenzamine or propranolol and serotonergic antagonist methergoline. It is concluded that BBS-induced suppression of feeding may be mediated through central BBS receptors, and is independent of interaction with brain catecholaminergic system. PMID- 7870885 TI - Role of benzodiazepine receptors located in the dorsal periaqueductal grey of rats in anxiety. AB - Studies with electrical brain stimulation suggest that the dorsal periaqueductal grey matter (DPAG) is related to anxiety and to the anti-aversive effects of benzodiazepines (BZD) compounds. However, direct stimulation of the brain may prevent conclusions about the role of specific regions in the control of normal behaviour. In the present study we employed the elevated plus-maze, an ethologically based model of anxiety, to investigate the role of BZD receptors located in the DPAG in anxiety and in the anxiolytic effect of systemically injected BZD. The results showed that midazolam (20-80 nmol), a BZD agonist, dose dependently increased the percentage of entries and time spent in open arms when microinjected into the DPAG. The effect of midazolam (80 nmol) was antagonized by flumazenil (80 nmol), a BZD antagonist, microinjected into the DPAG 10 min before the agonist. FG 7142 (20-80 nmol), a BZD partial inverse agonist, decreased time spent in open arms at the dose of 40 nmol and the number of open arms entries at all doses when microinjected into the DPAG. The microinjection of flumazenil (80 nmol) into the DPAG failed to antagonize the anxiolytic effect of systemically injected diazepam (2.5 mg/kg). These results strengthen the idea of an involvement of BZD receptors located in the DPAG with anxiety. They also suggest that the DPAG is not the only structure responsible for the anxiolytic effects of systemically injected BZD. PMID- 7870886 TI - Role of serotonin receptors in the effect of sertraline on feeding behaviour. AB - The effect of sertraline, a serotonin (5-HT) uptake inhibitor, on 1 h food intake of food-deprived rats was studied in male rats treated intraperitoneally with 1 and 2.5 mg/kg metergoline, a 5-HT1 and 5-HT2 receptor antagonist, 0.5 mg/kg GR 38032F, a 5-HT3 receptor antagonist, or intracerebroventricularly with 6-hydroxy dopamine to destroy catecholamine-containing neurons. The feeding-suppressant effect of 10 mg/kg sertraline was not significantly modified by any treatment. At 1 and 2.5 mg/kg metergoline did not significantly modify the reduction in total intake and meal size induced by sertraline in slightly-deprived rats whereas at 1 mg/kg the 5-HT receptor antagonist completely blocked the effect of 1.5 mg/kg d fenfluramine, a 5-HT releaser and uptake inhibitor. In a runway test, metergoline at 1 but not 2.5 mg/kg significantly attenuated the effect of 10 mg/kg sertraline on starting speed in the first and second trial blocks. Both doses tended to attenuate the effect of sertraline on running speed but the interaction was not significant. The reduction in food intake induced by sertraline was antagonized only by 1 mg/kg metergoline in the last trial block. The bulk of these findings argues against an important role of 5-HT receptors in the effect of sertraline on feeding behaviour. PMID- 7870887 TI - Central alpha-2 adrenoceptors are responsible for a clonidine-induced cue in a rat drug discrimination paradigm. AB - Clonidine produces an interoceptive discriminative stimulus or "cue" in rat drug discrimination studies. This cue may be mediated by its alpha-2 adrenoceptor agonist properties and/or its affinity for the non-adrenoceptor imidazoline preferring receptor. Six rats were trained to respond differentially after receiving clonidine (0.02 mg kg-1, IP) or a saline vehicle. The alpha-2 adrenoceptor agonists clonidine, UK14, 304 and rilmenidine, which bind to the imidazoline preferring receptor, and guanabenz which does not, dose-dependently substituted for (i.e. > 80% total responding was clonidine associated) the clonidine-induced cue in doses up to 0.02, 0.16, 1.25 and 0.32 mg kg-1, respectively. Furthermore, the cue was blocked when clonidine was given in combination with 30-min pretreatments of the highly selective alpha-2 adrenoceptor antagonists RX811059 (2.5 mg kg-1) and fluparoxan (3 mg kg-1). Since the clonidine-induced cue was substituted for by guanabenz, which does not act at the imidazoline-preferring receptor, and antagonised by RX811059 and fluparoxan it appears to be mediated by alpha-2 adrenoceptors. Moreover, abolition of the clonidine-induced cue did not occur with the peripherally acting alpha-2 adrenoceptor antagonist L659, 066 suggesting it involves central as opposed to peripheral sites. PMID- 7870888 TI - Ondansetron, an antagonist of 5-HT3 receptors, antagonizes the anti-exploratory effect of caerulein, an agonist of CCK receptors, in the elevated plus-maze. AB - Systemic treatment with caerulein (0.25-5 micrograms/kg SC), non-selective agonist of cholecystokinin (CCK) receptors, dose-dependently suppressed the exploratory behaviour of rats in an elevated plus-maze without producing remarkable changes in the locomotor activity of animals in an open field test. Ondansetron, a selective antagonist of 5-HT3 receptors, increased the number of open arm entries in the plus-maze test only at a dose 10 micrograms/kg. The other doses of ondansetron (0.1, 1 and 100 micrograms/kg IP) did not significantly change either the locomotor activity or the exploratory behaviour of rats. Pretreatment of rats with ondansetron (at 10 micrograms/kg, but not at 0.1, 1 or 100 micrograms/kg) completely reversed the anti-exploratory effect of caerulein (5 micrograms/kg). The concomitant treatment with caerulein and ondansetron did not cause any major change in the locomotor activity of animals in open field. Consequently, we propose that 5-HT-ergic mechanisms are involved not only in the regulation of CCK release in the cerebral cortex and nucleus accumbens, but also in the modulation of the anti-exploratory effect of caerulein, a CCK agonist, in the elevated plus-maze. PMID- 7870889 TI - Effects of chronic marijuana use on human cognition. AB - Impairments of human cognition and learning following chronic marijuana use are of serious concern, but have not been clearly demonstrated. To determine whether such impairments occurred, this study compared performance of adult marijuana users and non-users (N = 144 and N = 72, respectively) matched on intellectual functioning before the onset of drug use, i.e., on scores from standardized tests administered during the fourth grade of grammar school (Iowa Tests of Basic Skills). Subjects were given the twelfth grade versions of these tests (Iowa Tests of Educational Development) and other, computerized cognitive tests in successive test sessions. "Heavy" marijuana use (defined by use seven or more times weekly) was associated with deficits in mathematical skills and verbal expression in the Iowa Tests of Educational Development and selective impairments in memory retrieval processes in Buschke's Test. The retrieval impairments were restricted to words that were easy to visualize. Impairments depended on the frequency of chronic marijuana use, i.e., "light" and "intermediate" marijuana use (defined by use one to four and five to six times weekly, respectively) were not associated with deficits. Intermediate use was associated with superior performance in one condition ("fuzzy" concepts) of a Concept Formation test. PMID- 7870890 TI - Restoration of brain myo-inositol levels in rats increases latency to lithium pilocarpine seizures. AB - Lithium pretreatment in rats potentiates the epileptogenic effects of pilocarpine and other cholinergic agonists. In order to determine if this effect of lithium could be reversed by myo-inositol, rats were pretreated with intracerebroventricular (ICV) injections of myoinositol, artificial CSF or L chiro-inositol. Lithium chloride, 3 meq/kg was administered intraperitoneally 20 24 h prior to the subcutaneous injection of pilocarpine, 20 or 30 mg/kg. In both experiments, myo-inositol significantly prolonged the latency to the appearance of clonic seizures and lowered the pilocarpine seizure score. myo-Inositol prevented the development of clonic seizures in 50% of the rats receiving pilocarpine, 20 mg/kg. The levels of cortical myo-inositol in rats injected with myo-inositol were approximately double those of the CSF and L-chiro-inositol groups. PMID- 7870891 TI - Platelet 5-HT uptake sites in depression: three concurrent measures using [3H] imipramine and [3H] paroxetine. AB - Platelet 5-HT uptake sites were measured in 40 depressed patients and 40 controls using [3H] imipramine binding, defined with desmethylimipramine (DMI) and Na+ dependence, and [3H] paroxetine binding. In control subjects the Bmax of DMI defined [3H] imipramine binding was significantly higher than both Na+ dependent [3H] imipramine (by 30%) and [3H] paroxetine binding (by 22%). The Bmax of Na+ dependent [3H] imipramine and [3H] paroxetine binding did not differ significantly. The Kd of Na+ dependent [3H] imipramine binding was significantly lower than the Kd of DMI defined [3H] imipramine binding. The binding of DMI defined and Na+ dependent [3H] imipramine and [3H] paroxetine did not differ significantly between depressed patients and controls in the total group, in those depressed patients and controls in the total group, in those depressed patients who had never taken antidepressants or in those depressed patients who had been recently withdrawn from antidepressants. This study provides no support for the view that the number of platelet 5-HT uptake sites are reduced in depression. PMID- 7870892 TI - "One-trial tolerance" to the anxiolytic actions of benzodiazepines in the elevated plus-maze, or the development of a phobic state? AB - Diazepam (5 mg/kg) increased the number of shocks accepted by rats on two successive trials in the punished drinking test. Thus, the phenomenon of "one trial tolerance" to the anxiolytic effects of benzodiazepines in the elevated plus-maze does not generalise to this other animal test of anxiety. FG 7142 (20 mg/kg) and prior exposure to the odour of a cat had significant anxiogenic effects on two successive trials in the plus-maze. Thus the phenomenon of "one trial tolerance" does not generalise to these anxiogenic effects in the plus maze. Furthermore, chlordiazepoxide retained its ability to counteract the anxiogenic effects in the plus-maze of prior exposure to cat odour, over successive trials. On the basis of these and previous experiments it is suggested that the state of anxiety generated on trial 2 in the plus-maze is close to a phobic state, against which benzodiazepines are relatively ineffective. Chlordiazepoxide (5 and 10 mg/kg) was also ineffective against the behavioural responses of rats during exposure to cat odour, another possible animal test of phobia. This contrasted with its efficacy against the anxiogenic effects of cat odour that subsequently generalised to and could be detected in the plus-maze. PMID- 7870893 TI - Attenuation of antipredator defensive behavior in rats following chronic treatment with imipramine. AB - The anxiety/defense test battery has been developed to assess defensive reactions in rats to situations associated with a natural predator, the domestic cat. This comprises three paradigms designed to study the effects of cat exposure on general activity and location with respect to the cat (proxemic avoidance), the effects of cat exposure on non-defensive consummatory behavior, and the behavioral response to cat odor. In the present study subjects were exposed to 21 days pretreatment with imipramine (0, 5, and 15 mg/kg), before being assessed in the three experimental paradigms (carried out over a total period of 7 days). Imipramine treatment was maintained on a daily basis during the 7 days taken to complete the series of tests. The data indicated a behaviorally specific profile consistent with anxiety/fear reduction, but not with sedation, in three different paradigms, following treatment with 15 mg/kg imipramine. These behavioral changes included a reduction in freezing, proxemic avoidance and a disinhibition of suppressed feeding in response to cat presentation. Similarly, imipramine treatment (15 mg/kg) significantly reduced behaviors associated with risk assessment (e.g. flat back approach, stretch attend) during presentation of a cat odor stimulus. This behavioral profile suggests that chronic pretreatment with imipramine produces an attenuation of antipredator defensive behavior. PMID- 7870894 TI - Antagonism of the morphine-induced Straub tail reaction by kappa-opioid receptor activation in mice. AB - The Straub tail reaction (STR) induced by intracerebroventricular injection (ICV) of morphine was significantly antagonized by beta-funaltrexamine (beta-FNA, mu antagonist), given intracerebroventricularly (ICV), but not naltrindole given ICV (NTI, delta antagonist) or SC norbinaltorphimine given subcutaneously (SC) (nor BNI, kappa antagonist). When given either SC or ICV the kappa-agonist, U-50,488 H markedly suppressed the STR elicited by ICV morphine; these effects were reversed by nor-BNI. These results suggest that the activation of supraspinal kappa receptors can inhibit the ICV morphine-induced STR which results from activation of supraspinal mu receptors. PMID- 7870895 TI - Comparison of in vitro binding properties of a series of dopamine antagonists and agonists for cloned human dopamine D2S and D2L receptors and for D2 receptors in rat striatal and mesolimbic tissues, using [125I] 2'-iodospiperone. AB - We investigated the ligand binding properties in vitro of two splice variants of the cloned human dopamine D2 receptor (the 443 and 414 amino acids long forms called D2L and D2S, respectively), expressed in 293 human kidney cells, in comparison with those of the dopamine D2 receptors in rat striatum, nucleus accumbens and tuberculum olfactorium. The new radioligand, [125I]2' iodospiperone, showed a similar high binding affinity (KD:0.056-0.122 nM) for cloned human D2S and D2L receptors and for the D2 receptors in the three rat brain areas. Binding affinities of 25 dopamine antagonists and of 10 dopamine agonists belonging to different chemical classes were measured. The IC50 values of the antagonists were virtually identical in the five preparations: spiperone was the most potent compound (pIC50 approximately 9.9), remoxipride the least potent one (pIC50 approximately 5.7). The agonists showed similar IC50 values for the cloned human D2S and D2L receptors but their affinity for rat brain D2 receptors was 2- to 5-fold higher. Dopamine showed shallow inhibition curves, the high affinity binding was 10-fold lower for the cloned human D2 receptors than for the rat brain D2 receptors. Addition of stable guanosine-5'-triphosphate (GTP) analogues shifted the D2 receptors in the rat brain tissues to the "low" affinity state, the low affinity binding of dopamine was equal to the affinity for the cloned human receptor. None of the dopamine antagonists or agonists could differentiate between the two splice forms of the cloned human D2 receptors or between the D2 receptors in rat striatal and mesolimbic tissues. The lower apparent affinity of some agonists and of dopamine in the absence of stable GTP analogues suggests a less appropriate receptor G-protein coupling for the cloned human D2 receptors expressed in the 293 human kidney cells. Unexpectedly, guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S) reduced the [125I]2' iodospiperone binding to the D2 receptors by 20-35% in the rat brain tissues and the cloned human D2L receptor, and by 75% to the cloned human D2S receptor. The inhibition in the last case could be prevented partly by submicromolar concentrations of dopamine. The GTP-gamma-S effect is suggested to be due to reduction of disulphide bonds in the receptor. Recent molecular modelling studies indicated an important role of the disulphide bridge between Cys107 at the start of transmembrane domain three and Cys182 in the third extracellular loop, for the binding of dopamine to the D2 receptor. PMID- 7870897 TI - Does caffeine intake enhance absolute levels of cognitive performance? AB - The relationship between habitual coffee and tea consumption and cognitive performance was examined using data from a cross-sectional survey of a representative sample of 9003 British adults (the Health and Lifestyle Survey). Subjects completed tests of simple reaction time, choice reaction time, incidental verbal memory, and visuo-spatial reasoning, in addition to providing self-reports of usual coffee and tea intake. After controlling extensively for potential confounding variables, a dose-response trend to improved performance with higher levels of coffee consumption was observed for all four tests (P < 0.001 in each case). Similar but weaker associations were found for tea consumption, which were significant for simple reaction time (P = 0.02) and visuo spatial reasoning (P = 0.013). Estimated overall caffeine consumption showed a dose-response relationship to improved cognitive performance (P < 0.001 for each cognitive test, after controlling for confounders). Older people appeared to be more susceptible to the performance-improving effects of caffeine than were younger. The results suggest that tolerance to the performance-enhancing effects of caffeine, if it occurs at all, is incomplete. PMID- 7870896 TI - Beta-receptor responsiveness after desipramine treatment. AB - To examine whether a tricyclic antidepressant affects the functional response to a beta-receptor agonist in man, the response of heart rate, blood pressure, and plasma cAMP to isoproterenol was measured in 14 normal controls taking 75 mg desipramine daily. Desipramine significantly increased the bolus dose of isoproterenol needed to increase heart rate by 25 bpm at 14-30 days but not at 3 8 days. During infusions of isoproterenol, the increase in systolic blood pressure was blunted at both 3-8 days and 14-30 days, while the decrease in diastolic blood pressure was unaffected. Blood pressure findings were not affected by preadministration of bethanechol. In ten controls, isoproterenol infusions increased plasma cAMP, but this was unaffected by desipramine treatment. These findings suggest a decrease in the functional response of beta 1, but not beta 2, receptors after treatment with desipramine. PMID- 7870898 TI - Autoshaping i.v. cocaine self-administration in rats: effects of nondrug alternative reinforcers on acquisition. AB - The purpose of this experiment was to examine the effects of a nondrug alternative reinforcer and feeding conditions on the acquisition of cocaine self administration. Rats were autoshaped to press a lever that resulted in a 0.2 mg/kg i.v. cocaine infusion. Responses on the lever were monitored during six consecutive autoshaping sessions that occurred each day. A retractable lever was inserted into the operant chamber on a random time 60 s schedule 10 times per session for six sessions that began each hour. Each day the six autoshaping sessions were followed by a 6-h cocaine self-administration session. During self administration the lever remained extended, and each response on the lever resulted in a cocaine infusion (0.2 mg/kg). The criterion for acquisition of cocaine-reinforced behavior was met when there were 5 consecutive days during which the mean number of infusions during the 6-h self-administration session was at least 100. This procedure was repeated daily until the criterion was met or 30 days elapsed. The rats were also trained to respond on lick-operated automatic drinking devices that delivered 0.05 ml water or a glucose and saccharin solution (G + S) contingent upon each lick response. Five groups of 12-14 rats were compared. The first four groups constituted a 2 x 2 factorial design whereby either G + S or water was available in the home cage for 3 weeks before autoshaping began and G + S or water was available in the operant chamber during autoshaping. These groups were limited to 20 g food per day and all had free access to water.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870899 TI - The role of serotonergic mechanisms in inhibition of isolation-induced aggression in male mice. AB - The role of serotonergic (5-HT) receptor subtypes in mediation of aggressive behaviour in isolated male mice has been studied. Increase of attack latency was used as a simple measure of antiaggressive behaviour. 5-HT1A agonists (BAY R 1531, 8-OHDPAT, flesinoxan, gepirone, 5MeO DMT, buspirone, ipsapirone, BMY 14802) completely inhibit the aggressive behaviour irrespective of their intrinsic activities. Also the putative antagonists spiroxatrine and NAN 190 as well as the non-selective 5-HT1 agonists RU 24969, TFMPP, mCPP and eltoprazine have an antiaggressive effect. The mixed 5-HT1A and beta-adrenoceptor antagonists (-) alprenolol and pindolol are ineffective and do not inhibit the effect of 8 OHDPAT. Neither does the non-selective 5-HT antagonist metergoline. The antiaggressive effect correlates with 5-HT1A receptor affinity in vitro and with generalization to the 8-OHDPAT-induced discriminative stimulus. The selective 5 HT uptake inhibitor citalopram does not inhibit aggressive behaviour. The 5-HT2 agonist DOI has an antiaggressive effect only at high doses, whereas the 5-HT2 antagonist ritanserin and the 5-HT3 antagonist ondansetron are ineffective. Prazosin (alpha 1-adrenoceptor antagonist), clonidine (alpha 2-adrenoceptor agonist), clenbuterol (beta-adrenoceptor agonist), ketanserin (5-HT2 receptor and alpha 1-adrenoceptor antagonist), clozapine and (-)-octoclothepin (dopamine (DA), 5-HT2 receptor and alpha 1-adrenoceptor antagonist) all show an antiaggressive effect. SCH 23390 (DA D1 receptor antagonist) and emonapride (DA D2 receptor antagonist) are ineffective. In conclusion, 5-HT1A receptors are involved in mediation of isolation-induced aggressive behaviour in mice. The involvement of other 5-HT receptor subtypes needs further clarification. The adrenergic system may also be involved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870900 TI - Pharmacological specificity of enhanced sensitivity to naltrexone in rats. AB - Rats treated weekly with cumulative doses (1-100 mg/kg, IP) of naltrexone develop an enhanced sensitivity to the operant response-rate decreasing effect of naltrexone. In the present experiment the pharmacological specificity of that enhanced sensitivity was determined by testing a variety of drugs for cross sensitivity to naltrexone. Cross-sensitivity was evaluated with two procedures. In one, dose-effect functions were determined for each of the test compounds before and after the development of enhanced sensitivity to naltrexone in a single group of rats. In the second procedure, one group of rats was made sensitive to naltrexone, while a second was not. Test compounds were then evaluated in both groups. For both procedures, a shift to the left in the dose effect functions similar to naltrexone was considered evidence of cross sensitivity. Of the opioid antagonists tested, only naloxone showed clear cross sensitivity to naltrexone, although MR 2266 and diprenorphine also showed evidence of cross-sensitivity. The opioid antagonist quadazocine did not show cross-sensitivity to naltrexone on the day of testing, although some evidence of cross-sensitivity was evident 24 h later. In addition, the dose-effect function for d-amphetamine was significantly changed following naltrexone treatment. No evidence of cross-sensitivity was observed for the optical isomer of naloxone, d naloxone, or for naloxone's quaternary derivative, naloxone methiodide. None of the opioid agonists or agonist-antagonists tested showed cross-sensitivity to naltrexone (i.e. morphine, U-50, 488H, ethylketocyclazocine, N-allylnormetazocine and pentazocine). The non-opioid drugs chlordiazepoxide and phencyclidine also failed to show evidence of cross-sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870901 TI - Biphasic locomotor effects of the dopamine D1 agonist SKF 38393 and their attenuation in non-habituated mice. AB - The locomotor stimulatory effects of the dopamine D1 receptor partial agonist SKF 38393 were examined in male C57B1/6J mice. Non-habituated mice showed marked dose related (3-300 mg/kg, SC) locomotor stimulation. The time-course effect was biphasic at very high doses (100-300 mg/kg), with dose-related locomotor depression followed by dose-related long-term hyperlocomotion. For all doses, locomotor effects were detectable throughout the 4-h test period. To determine whether these effects were mediated by D1 receptor stimulation, effects of SKF 38393 were assessed in combination with behaviorally inactive and active doses (0.1 and 0.2 mg/kg, respectively) of the selective D1 receptor antagonist SCH 39166. Both doses of SCH 39166 attenuated the hyperlocomotion induced by 30 mg/kg of the agonist to a similar degree. However, neither dose was able to reverse either the depressant or the stimulatory effects of 300 mg/kg SKF 38393. These results demonstrate effects of the prototypical D1 agonist previously unobserved, and raise questions concerning the nature of agonist/antagonist interactions at the D1 receptor subtype. PMID- 7870902 TI - Morphine acts in the parabrachial nucleus, a pontine viscerosensory relay, to produce discriminative stimulus effects. AB - Morphine is known to act centrally to produce discriminative stimulus effects, but the specific neuroanatomical sites mediating this action have not been identified. We used morphine as a discriminative stimulus in a taste aversion paradigm to elucidate the neural basis of morphine's cueing properties. Rats were injected subcutaneously with 5 mg/kg morphine 15 min prior to the presentation of a 0.1% saccharin solution. After 20 min of exposure to the flavor, lithium chloride (130 mg/kg, IP) was injected. On alternate days, an injection of 0.9% physiological saline both preceded and followed the presentation of saccharin. Animals learned to consume significantly less saccharin after morphine than after saline injections. Unilateral guide cannulae were then implanted into brain areas containing relatively high densities of opiate binding sites, comprising the medial prefrontal cortex, the nucleus accumbens, the anterior dorsolateral striatum, the medial thalamus, the basolateral amygdaloid nucleus, the dorsal hippocampus, the caudal periaqueductal grey and the parabrachial nucleus. Generalization to central routes of administration was then evaluated by microinjecting morphine (2.5, 5, 10 and 20 micrograms) into these brain areas. Dose-dependent decreases in saccharin consumption similar to those of systemic morphine were produced by the administration of morphine into the parabrachial nucleus and the nucleus accumbens. Control data showed that only in the parabrachial nucleus could these effects be attributed to the cueing properties of morphine; in the nucleus accumbens, morphine administration induced unconditioned decreases in saccharin consumption. In the remaining brain areas, morphine generalized to the systemic saline condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870903 TI - Benzodiazepine pharmacodynamics: utility of eye movement measures. AB - The utility of several measures of saccadic and smooth pursuit eye movements as benzodiazepine pharmacodynamic measures was explored in 24 psychiatrically and medically health control subjects. Measures of sedation and memory impairment were also included. Subjects received four logarithmically increasing doses of intravenous diazepam at 15-min intervals on 1 day resulting in monotonically increasing plasma diazepam levels, and placebo on another day in random order 1 week apart. Measures were collected twice at baseline, once after each dose of diazepam/placebo and twice more, 15 and 30 min after the last dose. Peak saccadic velocity and smooth pursuit gain showed the greatest overall and dose-dependent drug effect among eye movement measures. Although effect sizes at the highest dose for memory impairment and self-rated sedation were comparable to these two measures, reliability (i.e., placebo-day fluctuation) with these measures was considerably poorer. Log-linear pharmacodynamic modeling was used to calculate the effective dose (ED30) or concentration (EC30) required to reduce saccadic velocity or pursuit gain by 30%. Almost all (23/24) subjects had linear and easily interpretable plots for saccadic velocity, while a majority (19/24) of subjects had interpretable plots for smooth pursuit gain. The distribution of ED30 and EC30 values showed a wide range of sensitivities to diazepam. These findings suggest that saccadic velocity and smooth pursuit gain are sensitive, reliable, quantitative benzodiazepine pharmacodynamic measures. PMID- 7870904 TI - Quantitative grip strength assessment as a means of evaluating muscle relaxation in mice. AB - The effects of various centrally acting drugs and some peripherally acting agents on the forelimb grip strength of CD-1 mice were explored. Forelimb grip strength was assessed by use of a strain gauge to measure the lateral pull force, in grams, exerted by mice as an index of muscle relaxation. The muscle relaxants, diazepam, midazolam, baclofen, methocarbamol, dantrolene sodium and the neuromuscular blocking agents, succinylcholine and pancuronium bromide, dose dependently reduced forelimb grip strength. 2-Amino-7-phosphonoheptanoic acid (AP7), which has also been shown to have muscle relaxant effects, also reduced grip strength. Pentobarbital, ethanol, phencyclidine, ketamine and chlorpromazine reduced grip strength at doses which produced behavioral impairments. Lithium chloride, a toxic compound used to induce taste aversions, and clonidine, at doses which affect blood pressure, body temperature and locomotor activity, did not affect grip strength. In addition, stimulant doses of amphetamine and caffeine, but not of morphine, increased grip strength in a dose-dependent manner. These results extend previous findings and suggest that this forelimb grip strength procedure may be a useful screening test for the identification of the potential muscle relaxant properties of drugs. PMID- 7870905 TI - Effects of serotonergic agents on apomorphine-induced locomotor activity. AB - The interactions of serotonin 5-HT1A, 5-HT1C/2 and 5-HT3 receptor subtypes with apomorphine-induced locomotor activity (AILA) were investigated in Sprague-Dawley rats. The 5-HT3 antagonists ondansetron and ICS 205-930 had no significant effects on AILA. The 5-HT1A agonist 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH DPAT) produced an increase in locomotor activity that was independent of DA neurotransmission. The locomotor activity induced by co-administration of apomorphine (APO; 0.25 mg/kg) and 8-OH-DPAT (0.25-1.0 mg/kg) was not significantly higher than those induced by APO alone during the peak period of APO stimulation of locomotor activity, nor were they higher than activity induced by 8-OH-DPAT alone during the same time intervals. The 5-HT1 antagonist (1) propranolol had a depressant effect on AILA, but only at high doses. Coadministration of (1)-propranolol (5 mg/kg) and 8-OH-DPAT (1.0 mg/kg) elevated spontaneous locomotor activity for the first 10 min of the session when compared to 8-OH-DPAT (1.0 mg/kg) alone. The 5-HT2 antagonist ketanserin along with moderate and high doses of mesulergine depressed AILA, effects which may be mediated by the 5-HT2 antagonist properties of these drugs, by nonspecific sedation or by direct effects of these compounds on DA D2 receptors. In contrast to the high-dose mesulergine depression of AILA, a low dose (0.1 mg/kg) of mesulergine elevated AILA, an effect which was blocked by the 5-HT1C/2 agonist 1 (2,-5-dimethoxy-4-iodophenyl) -2-aminopropane (DOI; 1 mg/kg). Neither of these compounds at the doses tested had significant effects on spontaneous locomotor activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870906 TI - Effects of ceruletide on the dopamine receptor-adenylate cyclase system in striatum and frontal cortex of rats chronically treated with haloperidol. AB - Chronic treatment of rats with haloperidol decanoate (30 mg/kg and 100 mg/kg IM every 4 weeks for 52 weeks) increased [3H] SCH 23390 binding in striatal membranes by 25% and 50% and in frontal cortical membranes by 56% and 125% in 30 and 100 mg/kg haloperidol treatment groups, respectively. These increases in [3H] SCH 23390 binding to the membranes were restored to control levels after ceruletide treatment (100 micrograms/kg IP twice a day for 5 days). [3H] Spiperone binding to the rat striatal and cortical membranes also increased after chronic haloperidol treatment (by 66% and 99% in striatal membranes and by 27% and 62% in cortical membranes in the 30 and 100 mg/kg haloperidol treatment groups, respectively). Administration of ceruletide to haloperidol-treated rats reduced the increased [3H] spiperone binding to the cortical membranes toward the control level, but ceruletide was not effective in reducing the haloperidol induced increase of [3H] spiperone binding to the striatal membranes. Activation of adenylate cyclase by dopamine (1 microM or 100 microM) or Gpp(NH)p (1 microM) was reduced in striatal and cortical membranes from haloperidol-treated rats. Ceruletide restored the lowered level of dopamine-stimulated or Gpp(NH)p stimulated adenylate cyclase activity in the membranes from haloperidol-treated rats to control levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870907 TI - Effects of serotonergic manipulations on cocaine self-administration in rats. AB - Rats were trained to self-administer cocaine (0.5 mg/kg/infusion) and were then pretreated with the 5-HT1A agonist 8-OH-DPAT (0.125, 0.25 or 0.5 mg/kg, SC). 8-OH DPAT pretreatment produced a decrease in reinforced response rates. When the effect of 8-OH-DPAT (0.5 mg/kg, SC) on responding for a range of cocaine doses was assessed, the drug produced a decrease in response rates when lower doses of cocaine served as the reinforcer. Fluoxetine (10 mg/kg, IV), an indirect 5-HT agonist, also reduced reinforced response rates for a low dose infusion of cocaine. Rates of responding for infusions of higher cocaine doses were not affected by fluoxetine pretreatment during an FR1 schedule of reinforcement. When an FR10 schedule of reinforcement was imposed, reinforced response rates for infusions of higher doses of cocaine were also reduced. Thus, under conditions that produce high rates of responding (low dose infusion or high ratio requirements for an infusion) fluoxetine reduced responding. This effect may be due to the effects at the 5-HT1A receptor, since 8-OH-DPAT produced a similar effect on cocaine self-administration. Given that the effects of these 5-HT agonists are observed only when low doses of cocaine serve as the reinforcer or when task demands are high, it is possible that the suppression of responding reflects an effect that is not specific to the reinforcing impact of cocaine. An alternative explanation for these effects incorporates a concept of unit cost/cocaine infusion that allows for direct comparison across studies that employ different reinforcement schedules. PMID- 7870908 TI - Further analysis of the cognitive effects of tetrahydroaminoacridine (THA) in Alzheimer's disease: assessment of attentional and mnemonic function using CANTAB. AB - Results of a placebo controlled cross-over trial (N = 89) of the anticholinesterase drug THA as a treatment for dementia of the Alzheimer's type (DAT) are reported, with reference to previous trials of the drug and the cholinergic hypothesis of aging and dementia. Using computerised tests sensitive to specific aspects of memory and attention, evidence is found for improvements in attentional function rather than memory, in patients with mild to moderate DAT. Although these improvements were significant, they were small and restricted to certain tests of attentional function. Nevertheless, they add to the growing body of evidence that the cholinergic system is involved in the control of attentional processes. The results will be relevant to future investigations into the therapeutic effects of enhancement of the cholinergic system in DAT sufferers. PMID- 7870909 TI - Lack of cross-sensitization between the locomotor-activating effects of bromocriptine and those of cocaine or heroin. AB - Rats were given daily injections of bromocriptine (5.0 mg/kg IP) or vehicle either in the home cage or in a test box equipped with photocells to measure locomotion. The animals were then tested in the photocell boxes for their locomotor response to cocaine (10.0 mg/kg IP), heroin (0.5 mg/kg IP), or quinpirole (0.1 mg/kg IP). Repeated bromocriptine in the test box but not in the home cage caused progressive increases in sensitivity to the locomotor stimulating effects of bromocriptine and increases in the subsequent sensitivity to quinpirole but caused only trivial signs of cross-sensitization to cocaine or heroin. Cross-sensitization to quinpirole was temporary; responsiveness to quinpirole decreased with further quinpirole injections. Lack of significant cross-sensitization between bromocriptine and either cocaine or heroin and lack of permanence of the cross-sensitization between bromocriptine and quinpirole raise questions as to the biological basis of psychomotor stimulant sensitization. PMID- 7870910 TI - The benzodiazepine antagonist flumazenil blocks the effects of CCK receptor agonists and antagonists in the elevated plus-maze. AB - Peripheral administration of the unsulphated cholecystokinin octapeptide (CCK 8us) led to an anxiogenic-like action in the elevated plus-maze model of anxiety in rats. Devazepide and L-365,260 showed potent anxiolytic-like effects at similar doses. The fact that devazepide is 1000 times more potent as a CCK-A receptor antagonist than L-365,260, whereas the two compounds are nearly equipotent at the CCK-B receptor subtype, suggests that CCK-B rather than CCK-A receptors are involved in these effects. Similar results were obtained in mice using the two-compartment test. In the elevated plus-maze, the benzodiazepine antagonist, flumazenil, which was inactive when given alone, significantly antagonized the anxiogenic-like activity of CCK-8us and the anxiolytic-like effects of devazepide and L-365,260. These results suggest a complex interaction between benzodiazepine and CCK receptor mechanisms in the regulation of anxiety states. PMID- 7870911 TI - Improved performance 4 hours after cocaine. AB - Cocaine (2 mg/kg) was given orally to 13 healthy volunteers and physiologic, subjective, attentional and performance effects were measured over a period of 4 h. Posner's reaction time paradigm measured the effects of cocaine on performance and on attention to visual cues. Cocaine increased heart rate, systolic blood pressure and pupil diameter and reduced skin temperature. Physiologic effects, subjective rating of intoxication, and cocaine levels in saliva peaked at approximately 75 min and returned to precocaine levels within 3 h. In contrast, a reaction time measure of performance speed on the visual attention task showed improvement for 4 h after cocaine. A measure of covert attention in the cocaine condition failed to show the improvement which occurred in the placebo condition. Less fatigue was reported 4 h after cocaine than after placebo. Cocaine users may experience the drug's stimulant effects considerably longer than the euphoriant effects. PMID- 7870912 TI - Effects of acute doses of oxiracetam in the scopolamine model of human amnesia. AB - The scopolamine model of amnesia has been used to test the pharmacodynamic efficacy of oxiracetam in 12 healthy volunteers. The subjects were divided into four experimental groups, according to a double-blind cross over incomplete randomized block design. After a baseline neuropsychological examination, each subject received in two separate sessions one of the following treatments, as acute oral doses: oxiracetam 800, 1600, 2400 mg or placebo. One hour after treatment scopolamine hydrobromide (0.5 mg) was given subcutaneously. The cognitive performance was tested before and 1, 2, 3 and 25 h after scopolamine administration. Scopolamine caused a deterioration of performance of verbal episodic memory, semantic memory and attention tests. In comparison to placebo, oxiracetam improved the overall test performance, with a statistically significant difference at the dose of 1600 mg on delayed recall of word lists, and showed dose-related antagonism of scopolamine-induced effects also on semantic memory and attention. The efficacy of an acute dose of oxiracetam in reducing scopolamine-induced cognitive impairment supports the potential usefulness of this pharmacological model of amnesia for studying the effects of cognition enhancers in humans. PMID- 7870913 TI - Interactions between chronic haloperidol treatment and cocaine in rats: an animal model of intermittent cocaine use in neuroleptic treated populations. AB - This experiment investigated the possibility that rats maintained on chronic haloperidol treatment would show increased behavioral responsiveness to cocaine, similar to that observed in human stimulant abusers who are chronically treated with neuroleptics. Thus, the effects on locomotion and stereotyped behavior of intermittent injections of cocaine were investigated in female rats receiving chronic haloperidol treatment. Daily injections of haloperidol (0.2 mg/kg, IP) or vehicle were administered for 6, 12 or 18 days prior to the start of testing with cocaine and were then continued throughout cocaine testing. All rats received four doses of cocaine (0.0, 3.0, 7.5, or 15.0 mg/kg, IP) in random order with an intervening vehicle day between successive drug days. The four dose sequence of cocaine was repeated a total of four times. Initial cocaine administration produced dose dependent increases in locomotion and stereotyped behavior. When the sequence of cocaine doses was repeated, differences among treatment groups emerged. Groups treated with haloperidol exhibited heightened locomotion in response to cocaine and with repeated injections, showed a higher rate of behavioral sensitization than control animals. These differences in the behavioral response to cocaine were maintained for at least 2 months following termination of daily haloperidol treatment. In order to examine the mechanisms underlying this heightened responsiveness to cocaine, apomorphine-induced locomotion (dose range, 0-250 micrograms/kg, SC) was determined. Regardless of dose, rats treated with haloperidol showed different temporal patterns of locomotion in response to apomorphine suggesting that the increased response to cocaine was related to changes in dopaminergic receptor sensitivity. PMID- 7870914 TI - Do double-blind studies with informed consent yield externally valid results? An empirical test. AB - Subjective and physiological effects of caffeine were investigated via a 3 x 2 x 3 design that assessed independent and interactive effects of instructions (told caffeine versus told no caffeine versus not told whether beverage contained caffeine), actual beverage content (caffeine versus no caffeine), and time after ingestion (15, 30, and 45 min). Instructions affected alertness at 15 min after ingestion. Caffeine increased alertness at 30 min after ingestion and systolic blood pressure at 30 min and 45 min after ingestion. A highly significant instruction by drug interaction on tension was obtained at all measurement points, indicating an increase in tension only among subjects who knowingly received caffeine. Because people are generally informed of drug content in non research settings, these data challenge the external validity of typical double blind studies, in which subjects are informed of the possibility of receiving a placebo as part of the consent procedure. PMID- 7870915 TI - Behavioral and neurochemical changes caused by repeated ethanol and cocaine administration. AB - Combined cocaine and ethanol abuse has become increasingly popular, yet research on the behavioral and neurochemical interactions of these two substances is limited. Four groups of male rats received either daily cocaine (10 mg/kg, IP) or saline injections with either water (groups C and S) or only 15% ethanol to drink (groups CE and E). Initially, locomotor activity was increased equally by ethanol or cocaine and to the greatest extent by both. After 2 weeks of drug treatment, group C exhibited behavioral sensitization to cocaine, group E exhibited ethanol tolerance and group CE exhibited greater cocaine sensitization with no indication of ethanol tolerance. In support of enhanced sensitization to cocaine, amphetamine-stimulated 3H-dopamine (DA) release in striatum and D2 DA receptor binding in the nucleus accumbens (NAC) were increased in group CE compared to group C. In support of a loss of ethanol tolerance, increases in striatal D2 DA and 35S-TBPS binding seen in group E (which exhibited ethanol tolerance) were absent in group CE (which did not exhibit tolerance). Thus, the synergistic effect of ethanol and cocaine on behavior may be due to complex interactions of these two drugs both on DA and GABA transmission in mesolimbic and nigrostriatal areas. PMID- 7870916 TI - "Anxiolytic" and "anxiogenic" benzodiazepines and beta-carbolines: effects on aggressive and social behavior in rats and squirrel monkeys. AB - Ethopharmacological studies on the behavior of socially housed rats and squirrel monkeys were conducted to explore the role of the benzodiazepine GABAA-coupled ionophore receptor complex in aggressive and social interactions. Benzodiazepine receptor (BZR) antagonists, ZK 93426 (1-10 mg/kg) and flumazenil (3-10 mg/kg), the partial agonist, ZK 91296 (1-10 mg/kg) and the partial inverse agonists Ro 15 4513 (0.3-10 mg/kg), were administered to (1) squirrel monkeys prior to 1 h focal observations within established social groups or to (2) resident male rats before confrontations with a naive male intruder in their home cage for 5 min. Aggression was modified in a similar manner in both species, although squirrel monkeys were more sensitive to BZR challenges. Specifically, resident male rats showed dose dependent reductions in attack bites directed at intruder males that were significant at the highest dose of ZK 93426 (10 mg/kg). In squirrel monkeys, ZK 93426 (3 and 10 mg/kg) reduced aggressive grasps, threats and displays, as well as reducing the duration of being the target of aggression from untreated group members (1-10 mg/kg). The BZR partial agonist, ZK 91296 and the antagonist, flumazenil produced few effects on social behavior, low and high intensity aggression and motor activity in both species. Flumazenil (10-30 mg/kg) and ZK 91296 (10 mg/kg), but not ZK 93426, produced significant increases in foraging and feeding behaviors in squirrel monkeys. The hyperphagic effects of ZK 91296 and flumazenil, that are typical of BZR agonists compounds, were not observed in rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870917 TI - Potentiation by low doses of selected neuroleptics of food-induced conditioned place preference in rats. AB - Numerous data support the hypothesis that dopamine (DA) plays a crucial role in reward-related processes and in incentive learning in animals and man. The possibility that various neuroleptics exhibiting a high affinity for the dopaminergic D2 (and D3) receptors could reinforce DA transmission was studied using the conditioned place preference paradigm (CPP) in rats. This was done by examining the ability of these compounds to potentiate the reinforcing properties of food in hungry rats subjected to a version of the CPP paradigm which consisted of repeated pairings of food with a single environmental cue, the floor texture of an open field. During the test session when food was no longer available in the open field, the increase in the time spent by drug-free rats on the food paired texture was assumed to indicate the perceived rewarding value of the food. This time was significantly lengthened when the specific D2 (D3)-receptor antagonists sulpiride (4 mg/kg), amisulpride (0.5, 1 mg/kg) or pimozide (0.03, 0.06 mg/kg) were administered before the food conditioning sessions. Larger doses of these compounds as well as haloperidol, metoclopramide and the non-specific D1 D2 antagonist, chlorpromazine, regardless of the doses tested, did not exhibit this effect, but rather reduced the food-induced CPP, an action usually associated with neuroleptics. The positive effects of amisulpride was reversed by a D1 receptor antagonist, SCH 23390 (0.01 mg/kg). These results suggest that, as with amphetamine (0.5 mg/kg), some D2-specific neuroleptics enhance the incentive value of food in a narrow range of low doses, an effect proposed to reflect a "prohedonic" property.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870918 TI - Sound vibration, a non-invasive stress: antagonism by diazepam. AB - Rats, subjected to sound-vibration stress, showed an abrupt increase in plasma corticosterone (CS). This stimulation was reliably produced using a Burgess brand "vibro-graver," a standard tool used for engraving. With the tool set at "8" or coarse, the barrel of the tool was placed on the animal's flank and the point held against the side of the metal cage for 15 s. Plasma CS increased to 29.3 +/- 4.7 micrograms/dl at 15 min and 15.7 +/- 1.8 micrograms/dl at 30 min. These levels were significantly higher than animals pretreated with diazepam, 5 mg/kg i.v., 2 h prior to stimulation (9.2 +/- 2.0 and 7.4 +/- 1.5 micrograms/dl, respectively). Animals which were pretreated with CGS-8216 (a mixed agonist/antagonist at the benzodiazepine receptor), 2 mg/kg i.v., 30 min prior to diazepam had the protective effects of diazepam abolished. Sound/vibration produced a significant elevation in plasma CS in animals given CGS-8216 alone; but, this elevation was significantly lower than in vehicle-treated controls. This comparatively lower plasma CS level suggests a partial-agonist, diazepam like effect by CGS-8216. Experiments were done in conscious unrestrained male Sprague-Dawley rats with chronic i.v. catheters. Except for 15 s stimulation exposure, all animals remained isolated in sound-attenuated one-way vision boxes for the duration of the serial blood sampling. Control stimulation exposure involved similar handling without turning on the engraving tool. These results demonstrate: 1) the usefulness of this tool to provide a repeatable stress stimulus; 2) the ability of diazepam to abolish the stress response; 3) that CGS 8216 can antagonize the action of diazepam; and 4) a demonstration of the partial agonist effects of CGS-8216. PMID- 7870919 TI - Pharmacodynamic interactions of diazepam and intravenous alcohol at pseudo steady state. AB - Pharmacodynamic interactions of low doses of diazepam and alcohol were investigated in a double blind, randomised, 2 x 2 factorial, cross-over study in eight healthy volunteers. Alcohol or glucose 5% were administered intravenously at rates calculated to maintain breath alcohol levels of 0.5 g/l from 1.5 to 5.5 h after starting the alcohol infusion. Diazepam 5 mg or placebo were administered orally at 1.5 h. Evaluation of pharmacodynamic interactions was performed for the average results of tests performed at 2, 3.5 and 5 h. Plasma concentrations of (desmethyl-) diazepam and breath alcohol levels were measured for pharmacokinetic analysis. Breath alcohol reached pseudo steady state levels of 0.38 g/l (range: 0.24-0.57) after alcohol alone and 0.37 g/l (range: 0.27-0.52) in combination with diazepam. Alcohol effects were demonstrated for latency of saccadic eye movements, smooth pursuit eye movements and subjective drug effects. Diazepam impaired smooth pursuit and saccadic eye movements, adaptive tracking, digit symbol substitution and body sway. The effects of combined alcohol and diazepam were mostly additive without significant synergistic interactions. However, in two subjects large supra-additive effects occurred at 3.5 h following alcohol+diazepam, which were not explained by increased drug levels. The design and methods used in this study proved advantageous in evaluating low dose pharmacodynamic interactions. Despite the absence of significant synergistic interactions, unanticipated impairment of performance may occur in susceptible individuals when taking combined low doses of alcohol and diazepam. PMID- 7870920 TI - Differential effects of intra-accumbens and systemic amphetamine on latent inhibition using an on-baseline, within-subject conditioned suppression paradigm. AB - Latent inhibition (LI) is a phenomenon in which repeated, non-reinforced presentation of a stimulus retards subsequent conditioning to that stimulus. Several recent experiments have suggested that LI is abolished following acute, low doses of amphetamine given during pre-exposure and conditioning, and this effect has been attributed to amphetamine-induced changes in dopamine levels in the nucleus accumbens. Experiments 1 and 2 examined the effects of two doses of intra-accumbens d-amphetamine (10 micrograms/microliters and 3 micrograms/microliters) on LI in an on-baseline, within-subject conditioned suppression paradigm. There was no effect of either dose on LI, but a significant disinhibition of conditioned suppression resulted in a retardation of learning. In experiment 3 the effects of a low dose of systemic d-amphetamine (0.5 mg/kg) on latent inhibition were examined. The results replicated the abolition of LI found in previous studies, and demonstrated enhanced post-shock suppression in amphetamine-treated animals. These data provide no evidence for the involvement of the mesolimbic dopamine system in LI. PMID- 7870921 TI - Modulation of nicotine-induced analgesia by calcium agonist and antagonist in adult rats. AB - The involvement of calcium in nicotine-induced analgesia in male rats was explored using the tail-flick test. A single dose of nicotine (1 mg/kg SC) produced a maximal effect on tail-flick latency (15 s) within 8-10 min, which lasted for 4 min. Pretreatment with the calcium chelator, EDTA (250 microM/kg SC four injections at 15 min intervals), before the single dose of nicotine accelerated the onset and prolonged the duration of the nicotine-induced analgesia. The maximal effect on tail-flick latency occurred within 2 min and lasted for 10-20 min. Conversely, pretreatment with calcium chloride (1.5 mM/kg IP) attenuated nicotine-induced analgesia. It is suggested that nicotine may exert its antinociceptive effects via modulation of calcium fluxes across the neural membrane. PMID- 7870922 TI - An ATP-sensitive potassium channel blocker abolishes the potentiating effect of morphine on the bicuculline-induced convulsion in mice. AB - ICV bicuculline, a selective GABAA antagonist, dose-dependently induced clonic tonic convulsions in mice. Coadministration of ICV morphine (mu opioid agonist) significantly potentiated ICV bicuculline-induced convulsions, and this effect of morphine was completely blocked by pretreatment with beta-funaltrexamine (beta FNA), a mu antagonist. ICV glibenclamide, a selective ATP-sensitive potassium (KATP) channel blocker, at a dose which alone did not affect the convulsive threshold of bicuculline, was capable of blocking the exacerbation of ICV bicuculline-induced convulsions by morphine. The present data further suggest that KATP channels may play a tonic regulatory role in the potentiative effect of morphine on ICV bicuculline-induced convulsions. PMID- 7870923 TI - Stimulant drugs and vigilance performance: a review. AB - The literature on the effects of some stimulant drugs (amphetamine, methylphenidate, caffeine, and nicotine) on vigilance performance is reviewed. Improvement of overall level of performance (both accuracy and speed) after the intake of amphetamine, caffeine, and nicotine has often been reported, and the decrement in performance with time has been shown to be prevented especially with amphetamine and nicotine. Effects on false alarms are negligible. In studies where a test battery was employed, vigilance tasks appeared to be the most sensitive performance tests in detecting the effects of stimulants; however, different vigilance tasks may measure different aspects of mental functions. There is no support for earlier conclusions that improvements are noticed only in fatigued subjects in protracted sessions. Evidence from several studies does not support the hypothesis that improvements are only a recovery of withdrawal induced impairment. Because positive effects have been obtained with drugs possessing different mechanisms of action, there is as yet no clear support for a noradrenergic, dopaminergic, or cholinergic theory of sustained attention. Simple neurotransmitter theories of attention and information processing may be untenable. PMID- 7870924 TI - Is the dopaminergic system involved in the central effects of nicotine in mice? AB - Pretreatment with ineffective doses of the D1 antagonist SCH23390 but not the D2 antagonist sulpiride reduced hyperactivity induced by nicotine in mice habituated to the test cage. On the other hand, the D1 and D2 antagonists were ineffective in blocking nicotine-induced hypoactivity in naive mice. Finally, SCH23390 and sulpiride did not block the antinociception induced by nicotine. Our data indicate that the dopamine receptors D1 and D2 are not involved in all the central effects of nicotine in mice, but seems to be a substrate for locomotor activation induced by nicotine under specific experimental conditions. PMID- 7870925 TI - Environmental and pharmacological sensitization: effects of repeated administration of systemic or intra-nucleus accumbens cocaine. AB - The effects of repeated systemic or intra-nucleus accumbens cocaine administration on locomotor activity were examined for environmental dependence. Repeated IP administration of cocaine (15 mg/kg) for 5 days in the context of a given environment increased the locomotor response to a subsequent IP cocaine challenge in that environment. However, there were no differences in the locomotor response to a subsequent IP cocaine challenge in the test chamber in subjects which had received prior repeated IP administration of cocaine in the home-cage. In a second experiment, cocaine (100 micrograms/side) was infused into the nucleus accumbens (NACC) daily for 5 days. This repeated administration produced increases in locomotor activity to subsequent intra-NACC cocaine infusions that were environmentally independent. In contrast to the effects of repeated IP cocaine administration, subjects which received administration of vehicle, acute cocaine, or repeated cocaine in the NACC did not differ following an IP cocaine challenge. The results from these experiments indicate that increases in the response to IP cocaine following repeated IP administration are in part environmentally dependent. Moreover, repeated intra-NACC cocaine infusions increase the responsiveness of the NACC to subsequent intra-NACC cocaine. However, local activation of the NACC alone does not appear to be adequate to produce sensitization to systemically administered cocaine. PMID- 7870926 TI - Visual effects of opiates in pigeons. III. Luminance and wavelength sensitivity. AB - In a psychophysical task that permitted dissociations among sensitivity, overall stimulus control, and bias, pigeons learned to discriminate among stimuli along separate wavelength and luminance dimensions. Subsequent tests followed injections of morphine (1-8 mg/kg) and morphine plus naloxone (3 mg/kg). Morphine decreased sensitivity to both dimensions, and reduced overall control by luminance. These effects were reduced or reversed by naloxone. Morphine's effects appeared more pronounced for luminance than for wavelength stimuli. There were no consistent drug effects on response bias. PMID- 7870927 TI - Roxindole, a dopamine autoreceptor agonist, in the treatment of major depression. AB - Roxindole is a potent autoreceptor-"selective" dopamine agonist originally developed for the treatment of schizophrenic syndromes. The drug also inhibits 5 HT uptake and has 5-HT1A agonistic actions. In this open clinical trial 12 in patients suffering from a major depressive episode (DSM-III-R) were treated with roxindole for 28 days in a fixed dosage of 15 mg per day. A reduction of at least 50% in HAMD-17 total scores was observed in 8 out of 12 patients after 4 weeks (mean HAMD-17 reduction of 56% in all patients), while 4 patients did not respond to roxindole treatment. Half of the patients showed a complete psychopathological remission (HAMD-17 < 8). Roxindole's onset of antidepressant action was remarkably rapid. Seven out of eight responders improved within the first 2 weeks of treatment (at least 50% decrease in HAMD-17 total score), and four patients were nearly asymptomatic within 1 week. Our results indicate that roxindole may possess potent antidepressant properties and that its efficacy should be further evaluated by double-blind controlled studies against reference drugs. PMID- 7870928 TI - Aggression modulates genetic influences on morphine analgesia as assessed using a classical mendelian cross analysis. AB - Pharmacogenetic techniques allow for the examination of genetic and environmental factors underlying phenotypes associated with drug response. Initial studies of mice bred at Jackson Laboratories (JAX) indicated that C57BL/6J mice were more sensitive to morphine-induced analgesia, as measured by latency to paw lick, than SJL/J mice. A classical Mendelian cross breeding program was initiated in which F1, F2 and backcross generations were derived from C57BL/6J and SJL/J breeding pairs purchased from JAX to examine the genetic factors underlying morphine analgesia. Genetic analysis indicated significant dominance or heterosis for a reduced drug response. The F1 generation was less sensitive to morphine-induced analgesia than either parental strain. Mathematical analysis of the generation means revealed that a simple dominance model with no epistatic interaction between genes best described the data. Environmental factors also affected sensitivity to morphine analgesia, in that C57BL and SJL mice raised in our facility did not differ in latency to paw lick. SJL mice from JAX exhibit a high degree of aggression, while SJL mice raised in our facilities show little or no aggression. The levels of aggression among groups of SJL mice were characterized and found to correlate with sensitivity to morphine analgesia. Mice exposed to increasingly greater levels of aggression were the least sensitive to morphine. Thus, the changes observed in sensitivity to morphine-induced analgesia appear to be related to the degree of aggression to which these mice are exposed, possibly resulting from the stress and/or prolonged exposure to painful stimuli associated with aggressive encounters. PMID- 7870929 TI - Age and sex differences of dehydroepiandrosterone sulfate (DHEAS) and cortisol (CRT) plasma levels in normal controls and Alzheimer's disease (AD). AB - In 50 healthy subjects (23 female, 27 male, aged 18-81) and 24 patients with Alzheimer's disease (AD) (11 female, 13 male, aged 58-88) DHEAS and CRT plasma levels were studied. In normal subjects there was a clear negative correlation of DHEAS to age, while no significant age correlated decrease of CRT plasma levels was found. There was a significant decrease in the DHEAS/CRT ratio in elderly controls (aged > 60) as compared to young individuals (aged < 45). Overall there was a trend to lower DHEAS/CRT ratios in AD patients compared to age matched controls out of the total group of normals (P < 0.1), there was a significant decrease of this ratio in female AD patients (P < 0.05), compared to age matched female controls, but there was none in male Alzheimers; furthermore there was a significant difference in CRT plasma levels between female AD patients and age matched female controls (P < 0.01) and between female and male AD patients (P < 0.05). Considering the antiglucocorticoid effects of DHEAS, this ratio may account for its protective effect against hippocampal degeneration caused by glucocorticoids and possibly for the higher rate of AD in females. PMID- 7870930 TI - Interaction study between remoxipride and biperiden. AB - Twelve healthy male volunteers took part in a double-blind randomised cross-over study composed of three treatment sessions: remoxipride 100 mg; remoxipride 100 mg plus biperiden 4 mg; and biperiden 4 mg. Plasma and urine concentrations of remoxipride and biperiden, plasma prolactin levels, salivary flow and adverse events were recorded to assess pharmacodynamic interactions. Remoxipride and biperiden had no effect on each other's plasma concentrations. Biperiden did not affect the urinary recovery or renal clearance of remoxipride. Prolactin levels were unaffected by biperiden but increased following remoxipride administration. Differences in prolactin Cmax and tmax following remoxipride versus concomitant (remoxipride + biperiden) treatment were not statistically significant. However, a slight but statistically significant (P = 0.04) increase in prolactin AUC was observed after concomitant treatment. No significant differences could be observed between the recorded salivary flow in all the treatment sessions. Single doses of remoxipride and biperiden showed no pharmacokinetic or pharmacodynamic interaction. PMID- 7870931 TI - Impaired acquisition of swimming navigation in adult mice exposed prenatally to oxazepam. AB - Prenatally administered oxazepam (OX) impairs adult radial maze performance in mice, possibly by permanent hippocampal changes. CDI mice were tested in swimming navigation, a sensitive indicator for hippocampal damage. Ten males and ten females were exposed to OX on fetal days 12-16 by maternal administration PO of 30 mg/kg/day and fostered at birth to untreated dams, while control mice received vehicle solution. All mice were tested at 8-9 weeks for ability to find a submerged platform in a fixed location (acquisition: 18 trials, 6 trials per day) and for capacity to re-orient towards a new platform position (reversal: 12 trials, 6 trials per day). OX mice showed a slight but significant impairment of swimming navigation during the initial part of training, as indicated by longer swimming paths during the fourth and fifth trial (day 1), an impairment due both to delayed habituation to the novel stressfull condition and acquisition of platform climbing but unrelated to navigational abilities. No treatment-dependent differences were observed in the reversal phase. During reversal, both OX and control females spent significantly more time in swimming across the location of the old platform. Unrelated to navigational performance, females showed a slightly but significantly higher swimming speed than males. Due to the absence of any navigational impairment, data suggest that prenatal exposure to oxazepam exerts long-term influence on adult learning capacities primarily through interaction with brain systems located outside the hippocampus. PMID- 7870932 TI - Concurrent cocaine-ethanol ingestion in humans: pharmacology, physiology, behavior, and the role of cocaethylene. AB - Simultaneous abuse of cocaine and ethanol is a common occurrence. Cocaethylene, the ethyl ester of benzoylecgonine, has been detected in the urine of patients reporting concurrent use of cocaine and ethanol, and high levels have been found in the blood of victims of fatal drug overdose. This placebo-controlled, double blind study examined the pharmacokinetic, physiologic, and behavioral effects of dual cocaine and ethanol administration in humans (n = 6). Cocaethylene was found in the plasma only after administration of both cocaine and ethanol, and appeared to be eliminated more slowly than cocaine. Plasma cocaine concentrations were significantly higher during cocaine/ethanol administration. Euphorigenic effects were both enhanced and prolonged, and heart rate was significantly increased, following cocaine/ethanol administration as compared to administration of cocaine or ethanol alone. PMID- 7870933 TI - Serotonergic influences on male sexual behavior of rhesus monkeys: effects of serotonin agonists. AB - Although numerous studies in rats have demonstrated an influence of serotonin (5 HT) on male copulation, no studies have yet to demonstrate whether such a relationship exists in primate species. The present study sought to characterize 5-HT influences on male copulatory behavior of rhesus monkeys by using three different 5-HT agonists: a full 5-HT1A agonist, 8-hydroxy-2-(din-propylamino) tetralin (8-OH-DPAT); a partial 5-HT1A agonist, ipsapirone; and a 5-HT 1C/ID agonist, m-chlorophenylpiperazine (m-CPP). 8-OH-DPAT had a biphasic effect upon ejaculation latency, with low doses (5-10 micrograms/kg) producing a shortening of ejaculation latency (time from initiation of copulation to ejaculation), and the highest dose (100 micrograms/kg) producing a lengthening of ejaculation latency. Intromission frequency (number of intromissions preceding ejaculation) was affected only at 10 micrograms/kg 8-OH-DPAT with monkeys requiring fewer intromissions to ejaculation at this dose. Ipsapirone administration led to a shortening of ejaculation latency at all doses tested (50-800 micrograms/kg), and a reduction in intromission frequency at 200-800 micrograms/kg ipsapirone. Administration of the 5-HT 1C/1D agonist, m-CPP, resulted in an increase in ejaculation latency at 200-400 micrograms/kg m-CPP and mount latency at 400 micrograms/kg m-CPP, but did not affect intromission frequency. In summary, stimulation of 5-HT1A receptors lowered the ejaculatory threshold of the monkeys, while stimulation of 5-HT 1C/1D receptors interfered with copulatory behavior and raised the ejaculatory threshold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870934 TI - The discriminative stimulus properties of buspirone involve dopamine-2 receptor antagonist activity. AB - To investigate a dopaminergic component in the discriminative stimulus properties of buspirone, rats were trained to discriminate 2.5 mg/kg buspirone from saline, using a two lever, food-rewarded, fixed ratio 10 operant procedure. To test the dopamine-2 (D2) antagonist action of buspirone, a second group of rats was trained to discriminate 0.16 mg/kg apomorphine from saline. In addition to a complete generalization to 8-OH-DPAT, the D2 antagonists haloperidol, R 79598 and sulpiride showed a partial generalization to buspirone. The benzodiazepine ligands chlordiazepoxide and bretazenil did not generalize to the buspirone cue. Buspirone (2.0 mg/kg) completely blocked the apomorphine cue in the apomorphine trained rats. Haloperidol, R 79895 and sulpiride also blocked the apomorphine cue, although at doses much smaller than the doses needed to evoke buspirone responding in the buspirone trained group. 8-OH-DPAT did not antagonize apomorphine. It was concluded that the D2 action of buspirone partially contributes to its discriminative stimulus properties. Mediation of the buspirone cue by 5-HT1a receptor activation seemed predominant. Further, buspirone can act as a full D2 antagonist in drug discrimination. A model was proposed suggesting a compound discriminative stimulus complex of buspirone with a dominant 5-HT1a component that overshadows a less pronounced D2 component. PMID- 7870935 TI - Low and high doses of midazolam differentially affect hypoalgesia in rats conditioned to a heat stressor. AB - These experiments examined the effects of a benzodiazepine (midazolam) on rats' sensitivity-reactivity to the heated floor of a hot-plate apparatus. Rats were either previously exposed to the heated floor, or naive to the hot-plate apparatus, while control rats were familiarized with the apparatus in the absence of pain. A low dose (0.63 or 1.25 mg/kg) of midazolam attenuated the conditioned hypoalgesic response resulting from pre-exposure to a heated floor, but did not affect the hypoalgesic response elicited by exposure to a novel hot-plate apparatus nor the "baseline" sensitivity-reactivity among control rats. A high dose (2.5 mg/kg) of midazolam resulted in a naloxone-insensitive increase in both the conditioned and the novelty-induced hypoalgesia, and provoked a small, but naloxone-reversible increase in paw-lick latencies among control rats. The results were taken to mean that exposure to the heated floor results in hypoalgesic responses as a consequence of fear conditioning and the reinstatement of novelty. Midazolam was assumed to attenuate conditioned hypoalgesia by reducing fear but at the high dose to augment the hypoalgesic effects of novelty. PMID- 7870936 TI - Serotonin involvement in the discriminative stimulus effects of kappa opioids in pigeons. AB - The purpose of the present study was to examine the role of serotonin (5HT) in the discriminative stimulus effects of kappa opioids. Pigeons were trained to discriminate 5.6 mg/kg of the kappa opioid, U50,488, from water. During substitution tests, both U50,488 and another kappa opioid, spiradoline, produced > 80% responding on the U50,488-appropriate key. In contrast, the non-opioid compound, phencyclidine and several serotonergic compounds failed to substitute for the U50,488 discriminative stimulus across a wide range of doses. During combination tests, the selective 5HT1A agonist, 8-OH-DPAT (0.001-3.2 mg/kg), dose dependently attenuated the discriminative stimulus effects of 5.6 mg/kg U50,488 and 3.2 mg/kg spiradoline. This effect was reversed by the 5HT1A antagonist, NAN 190 (0.01-1 mg/kg), in a dose-dependent manner. Buspirone (0.01-10 mg/kg), a 5HT1A partial agonist, also attenuated the discriminative stimulus effects of the training dose of U50,488 but ipsapirone, another 5HT1A partial agonist, did not. Ketanserin, a 5HT2 antagonist, and MDL72222, a 5HT3 antagonist, attenuated the effects of U50,488, whereas the 5HT1B,1C agonist, mCPP, and the 5HT2 agonist, DOI, did not. Depletion of 5HT with p-CPA also attenuated U50,488's discriminative stimulus effects. Taken together, the results suggest that serotonin release is an important component in the discriminative stimulus effects produced by kappa opioids; however, the effects of DOI and mCPP alone suggest that activation of post-synaptic 5HT receptors is not sufficient to produce the full spectrum of kappa opioid discriminative stimulus effects. PMID- 7870937 TI - Effect of clonidine on the responsiveness of infant rats to maternal stimuli. AB - Clonidine (0.1 mg/kg), an alpha 2-adrenoceptor agonist, stimulated ultrasonic callings in 10-day-old rats. Unlike normal isolated rat pups, the vocalizations of clonidine-treated rats appeared resilient to maternal cues. Thus, clonidine induced vocalizations did not decrease during intraoral infusions with 10% sucrose, exposure to home cage bedding or tactile stimulation of the skin. Clonidine (0.05; 0.1; 0.2 mg/kg) also disrupted the attraction normally shown by infant rats to home cage odours in an olfactory place preference test. This effect by clonidine was not shared by raclopride (1-4 mg/kg), naltrexone (0.5-2.0 mg/kg) or propranolol (2.5-10.0 mg/kg). Clonidine-treated infants (0.05; 0.1; 0.2 mg/kg) also failed to apprehend and attach to the anaesthetized mother's nipple. The results raise the possibility that alpha 2-adrenoceptor activation blunts the infant's receptivity to maternal olfactory incentives and intensifies separation induced responses. PMID- 7870938 TI - Phencyclidine disrupts long- but not short-term memory within a spatial learning task. AB - In the first experiment rats with 1, 2, 3 or 4 mg/kg phencyclidine (PCP), or saline injections were tested for acquisition or retention of a cheese board spatial task (dry land version of a water maze). Results indicate that relative to controls or rats with injections of 1 and 2 mg/kg PCP, rats with 3 or 4 mg/kg PCP injections were impaired in acquisition and retention of the task as measured by increased distances traveled to find the correct food location. This impairment was primarily observed in between days but not within days performance. In the second experiment rats with 4 mg/kg PCP or saline injections were tested for memory performance of a delayed spatial matching-to-sample task. Results indicate that relative to controls rats with 4 mg/kg PCP injections were not impaired at either 1-5 or 30 s delays. It is suggested that PCP through its blocking action of the NMDA receptor mediates long- but not short-term memory for spatial location information as well as the ability to retrieve previously learned spatial location information. PMID- 7870939 TI - Chronic benzodiazepine administration. XII. Anticonvulsant cross-tolerance but distinct neurochemical effects of alprazolam and lorazepam. AB - Tolerance to the sedative and anticonvulsant effects of benzodiazepines has been reported, but cross-tolerance among benzodiazepines is poorly characterized. To evaluate cross-tolerance between lorazepam and alprazolam in a reliable anticonvulsant pharmacodynamic model, we treated mice with either drug for 14 days, and with the two drugs sequentially for 7 days each. Pentylenetetrazole induced seizure thresholds were similar in mice treated for 14 days with lorazepam or alprazolam, 2 mg/kg/day. For both compounds, a discontinuation effect characterized by reduced seizure threshold occurred at 4 days after discontinuation. Substitution of alprazolam for lorazepam after 1 week, and vice versa, did not interrupt tolerance. [3H]flumazenil binding in vivo was downregulated in cortex after 14 days of either drug. However, binding was also reduced in hippocampus for lorazepam but not for alprazolam. Substitution of alprazolam for lorazepam resulted in downregulation in cortex only, similar to lorazepam alone. Conversely, substitution of lorazepam for alprazolam led to binding changes similar to lorazepam alone. These data demonstrate cross tolerance to the convulsant effects of pentylenetetrazole between lorazepam and alprazolam. However, effects of the two compounds on benzodiazepine receptor binding in hippocampus remain distinct. PMID- 7870940 TI - Effect of chlormethiazole, dizocilpine and pentobarbital on harmaline-induced increase of cerebellar cyclic GMP and tremor. AB - Administration to mice of harmaline (100 mg/kg SC) resulted in a greater than two fold increase in cyclic GMP in the cerebellum 15 min later. This response was inhibited by pretreatment 5 min before the harmaline with pentobarbital (ED50 6.5 mg/kg), chlormethiazole (ED50 10.4 mg/kg) and dizocilpine (ED50 0.5 mg/kg). Harmaline-induced tremor was inhibited by pentobarbital (ED50 30 mg/kg) and chlormethiazole (ED50 50 mg/kg) but not dizocilpine. The data demonstrate that the harmaline-induced tremor and cerebellar cyclic GMP rise are probably not associated. They also demonstrate that chlormethiazole is able to inhibit a biochemical response (the increase in cerebellar cyclic GMP) which results from increased glutamate function. PMID- 7870942 TI - Testing the effects of hypnotics on memory via the telephone: fact or fiction? AB - The two benzodiazapines used in this experiment, namely midazolam and flunitrazepam, have both been shown to have effects on memory processing in laboratory studies. In spite of the potential hazards involved in real life testing, it should be possible to replicate such findings in everyday environments and it is argued that a successful replication would be a very meaningful extension to the existing laboratory data. The present study was successful in producing significant "hangover" effects in healthy volunteers using a novel "user-friendly" telephone testing technique. Compared to placebo, the two hypnotics reduced speed of processing in tasks which required retrieval from long-term semantic memory (semantic verification) and the manipulation of material in working memory (syntactic reasoning). We suggest that this new method offers the potential for carrying out large-scale psychopharmacological studies with real patients and achieves a meaningful step forward in the search for ecological validity. PMID- 7870941 TI - Vacuous jaw movements induced by sub-chronic administration of haloperidol: interactions with scopolamine. AB - The present series of experiments was conducted to investigate the vacuous jaw movements induced by sub-chronic administration of haloperidol (HP). In the first experiment, daily injection of 0.4 mg/kg HP for 10 days increased vacuous jaw movements and decreased rearing behavior. The second and third experiments investigated the interaction between the effects of HP and the anticholinergic drug scopolamine. Co-administration of 0.5 mg/kg scopolamine with 0.4 mg/kg HP for 9 days reduced vacuous jaw movements and increased rearing responses relative to rats that received HP alone. Co-administration of HP with 0.25 mg/kg scopolamine for 9 days increased rearing relative to rats that received HP alone, but there was no effect of the lower dose of scopolamine on vacuous jaw movements. Administration of 0.5 mg/kg scopolamine plus 0.4 mg/kg HP on days 11 14 to rats that had received HP alone for 10 days reversed the effect of HP on rearing, but not on vacuous jaw movements. Rats that had received HP plus scopolamine for 10 days showed dramatic increases in vacuous jaw movements when scopolamine was withdrawn. Because vacuous jaw movements are produced within the first few days of administration, reduced by administration of scopolamine, and exacerbated by withdrawal of scopolamine, the pharmacological characteristics of these movements do not appear to bear a close relation to those of tardive dyskinesia in humans. The present results are consistent with the hypothesis that vacuous jaw movements in rats share some characteristics with Parkinsonian symptoms. PMID- 7870943 TI - Strain-dependent effects of post-training GABA receptor agonists and antagonists on memory storage in mice. AB - Post-training administration of the GABA-A and GABA-B receptor agonists muscimol and baclofen dose-dependently impaired retention of an inhibitory avoidance response in C57 mice, while improving memory consolidation in the DBA strain. By contrast, picrotoxin (blocker of GABA-activated ionophores), bicuculline (GABA-A antagonist) and CGP 35348 (GABA-B antagonist) dose-dependently improved retention in C57 mice and impaired it in DBA mice. These effects cannot be ascribed to non specific actions of the drugs on retention performance, as the latencies during the retention test of those mice that had not received footshock during the training were not lengthened by the post-training drug administration. The effects on retention performance induced by GABA agonists and antagonists are probably due to an effect on memory consolidation, since they are observed when the drugs are given at short, but not at long, intervals after training. These results are discussed in terms of possible interaction of GABA systems with endogenous opioid and dopamine systems, whose activation has been shown to produce strain-dependent effects on memory processes. The possible utilization of these results for a genetic behavioral approach with recombinant inbred (RI) mice is also considered. PMID- 7870944 TI - Differential modification of the rewarding effects of methamphetamine and cocaine by opioids and antihistamines. AB - We previously reported that the reinforcing effects of opioids are enhanced in combination with antihistamines. In the present study, effects of opioids and antihistamines on the reinforcing effects of psychostimulants such as methamphetamine and cocaine were investigated by utilizing the conditioned place preference procedure in rats. The place preference induced by methamphetamine was enhanced in combination with either morphine or chlorpheniramine, which produced additive and potentiative effects, respectively. In contrast, although the preference for cocaine was also enhanced by combination with these two drugs, morphine caused a potentiative effect and chlorpheniramine an additive one. In other words, the reinforcing effect of methamphetamine was differentially enhanced by opioids and antihistamines as compared to that of cocaine. These results suggest that the mechanism of reinforcing effect of methamphetamine is different from that of cocaine, resembling rather those of opioids. PMID- 7870945 TI - Prevention of the pro-aggressive effects of alcohol in rats and squirrel monkeys by benzodiazepine receptor antagonists. AB - Pharmacological manipulations at the benzodiazepine-GABAA-chloride ionophore receptor complex modify some of the behavioral and physiological actions of alcohol (ethanol). The interactions between alcohol, benzodiazepines and aggression were examined in similar ethopharmacological studies in squirrel monkeys and in rats in confrontations with conspecifics. Dominant male squirrel monkeys were tested (1) within their social groups, and (2) in dyadic confrontations with "rival" males from a different social group, and resident male rats were tested in their home cage in confrontations with an inexperienced male intruder. Low doses of alcohol (0.1-0.3 g/kg) increased aggressive behaviors in dominant squirrel monkeys and a subgroup of resident rats, whereas high doses of alcohol (1-3 g/kg) decreased aggression and produced marked motor incoordination. Individuals that showed alcohol-enhanced aggression were selected, and pretreated with benzodiazepine antagonists (flumazenil, ZK 93426) prior to alcohol administration. Both ZK 93426 (3 mg/kg) and flumazenil (10 mg/kg) blocked the aggression-enhancing effects of alcohol in dominant squirrel monkeys and resident rats in confrontations with conspecifics. Neither compound altered the reductions in aggression and increases in inactivity produced by high doses of alcohol. Interestingly, agonist-like increased feeding and inverse agonist-like reductions in social behaviors were observed simultaneously at the same dose of flumazenil, in the same individual and testing situation. ZK 93426 did not alter feeding but also reduced social behaviors. The two antagonists were also not equipotent in their interactions with alcohol. ZK 93426 reduced alcohol induced motor incoordination in squirrel monkeys, whereas flumazenil did not. In fact, flumazenil potentiated the effects of low doses of alcohol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870946 TI - Dextrorphan attenuates the behavioral consequences of ischemia and the biochemical consequences of anoxia: possible role of N-methyl-d-aspartate receptor antagonism and ATP replenishing action in its cerebroprotecting profile. AB - The acute anti-ischemic and anti-anoxic effects of dextrorphan (DX) were compared with those of dizocilpine (MK-801) in a variety of animal models, and in vivo and in vitro testings under anoxic conditions. DX reduced the incidence of death in ischemic mice and improved the rotarod performance of mice with brain ischemia. The ischemically-impaired memory of mice treated with DX markedly improved, as shown in the step-through type passive avoidance test, Morris water maze and in the habituation of exploratory behavior test. MK-801 likewise improved the water maze performance of the ischemically-impaired mice, but to a lesser extent. The step-through type passive avoidance performance of ischemic mice was not improved by MK-801. In the passive avoidance task with normal mice, DX, like MK-801, produced anterograde amnesia at doses higher than those needed to attenuate the behavioral effects of ischemia. DX, intravenously or centrally administered, markedly and dose-dependently reduced the incidence of death in mice receiving potassium cyanide (KCN). DX lessened the reduction in adenosine triphosphate (ATP) and increased lactate contents in mice dosed with KCN and also lessened the reduction in ATP in the TCA cycle and oxidative phosphorylation reactions caused by KCN (0.58 mmol/l), whereas MK-801 failed to show any effect on ATP formation pathways in vivo and in vitro, and failed to protect mice against KCN-induced lethal toxicity in vivo. In the in vitro studies, DX increased the adenylate kinase activity of the rat brain homogenate. DX was found to be a cerebroprotectant with anti-ischemic and anti-anoxic actions, the effects probably stemming from its N-methyl-d-aspartate receptor antagonistic property in cooperation with its ATP replenishing action. PMID- 7870947 TI - Acute effects of marijuana smoking on aggressive, escape and point-maintained responding of male drug users. AB - Aggressive, escape and point-maintained operant responding of male marijuana smokers were measured during six 25-min sessions conducted over an 8-h experimental day. Aggressive responding ostensibly subtracted points exchangeable for money from another subject. Escape responding protected the subject's counter from point subtractions initiated by the other subject for some period of time. Aggressive and escape responding were engendered by subtracting points from the subjects and maintained by initiation of intervals free of point subtractions. Point subtractions presented to the subjects were attributed to other persons. Subjects earned points exchangeable for money on a third response option. Subjects participated in one session prior to smoking and five sessions after smoking. Subjects smoked placebo or three different potencies of active marijuana cigarettes. Marijuana smoking effects on escape responding were not significant and depended upon the frequency of provocation. Point-maintained responding was decreased after marijuana smoking. Aggressive responding was increased for the first hour after smoking and returned to placebo levels later in the day. These effects of marijuana smoking on aggressive responding are discussed in terms of subject characteristics, particularly drug use history. PMID- 7870949 TI - Dopamine efflux during withdrawal from continuous or intermittent cocaine. AB - Daily, intermittent, subcutaneous cocaine injections produce sensitization, while the continuous administration of cocaine produces tolerance to the behavioral effects of subsequent cocaine injections. The present experiments examined whether these behavioral differences are related to differences in the ability of cocaine to increase extracellular dopamine. Increases in perfusate DA, in response to different concentrations of cocaine, were measured in caudate-putamen slices obtained from rats withdrawn for 7 days from a 14-day treatment of either continuous or daily subcutaneous cocaine injections. Compared to saline controls, cocaine-induced DA efflux was increased in subjects receiving daily injections and markedly decreased in subjects receiving continuous cocaine. Thus, different temporal patterns of cocaine administration produce dramatically different alterations in DA neurotransmission. Such changes in dopamine release may be related to the withdrawal symptoms experienced by human cocaine abusers. PMID- 7870948 TI - Suppression of behavioral activity by norfenfluramine and related drugs in rats is not mediated by serotonin release. AB - Fenfluramine, a phenalkylamine with serotonin (5-HT) releasing properties, decreases motor activity in rats. The following studies assessed the contribution of 5-HT release to the behavioral effects of fenfluramine and norfenfluramine using a behavioral pattern monitor that simultaneously assesses locomotor and investigatory behavior. First, both fenfluramine and its active metabolite d norfenfluramine dose-dependently reduced locomotor and investigatory activity. The norfenfluramine-induced reduction in activity was not antagonized by pretreatment with the 5-HT uptake inhibitor fluoxetine or the 5-HT synthesis inhibitor p-chlorophenylalanine, drugs that reduce drug-induced 5-HT release. Second, the d- and l-enantiomers of norfenfluramine were nearly equipotent at reducing behavioral activity, although d-norfenfluramine is more potent as a 5-HT releasing agent. Third, p-chloroamphetamine, a drug that shares the 5-HT releasing properties of fenfluramine produced locomotor hyperactivity in the same paradigm. Previous studies indicate that other 5-HT releasing phenalkylamines have behavioral effects resembling those of p-chloroamphetamine rather than those of fenfluramine. Finally, a structurally related drug, 4-methoxy-5-methyl aminoindan (MMAI), produced dose-dependent reductions in behavioral activity that are similar to the effects of fenfluramine. The behavioral effects of MMAI were not antagonized by fluoxetine or by the 5-HT receptor antagonist methiothepin. These data suggest that the decrease in activity induced by fenfluramine, norfenfluramine and the related drug MMAI is not related to 5-HT release. PMID- 7870950 TI - Effect of the benzodiazepine receptor agonist, zolpidem, on palatable fluid consumption in the rat. AB - Two experiments examined the effect of the benzodiazepine receptor agonist, zolpidem, on palatable fluid intake in water-deprived rats. In the first experiment, pretreatment with 3.0 or 10.0 mg/kg zolpidem IP was found to increase consumption of a novel glucose drink (3% d-glucose and 0.15 sodium saccharine w/v in water). The increase in fluid consumption induced with zolpidem was comparable to the increases observed with diazepam and the benzodiazepine partial agonist, FG 8205. Experiment 2 demonstrated that this zolpidem-induced increase in drinking could be observed in both naive rats and in rats that had been habituated to the glucose drink and the testing environment: pretreatment with 3.0 mg/kg PO of zolpidem was found to increase fluid consumption in rats that had received either 0 or 8 days pre-exposure to the testing conditions. Contrary to earlier reports, these results support the conclusion that zolpidem, like other benzodiazepine agonists, can directly modulate ingestive behaviour. PMID- 7870951 TI - 22-28 kHz ultrasonic vocalizations associated with defensive reactions in male rats do not result from fear or aversion. AB - This study was carried out to determine whether 22-28 kHz vocalizations emitted during intermale interactions in adult rats were related with a state of fear, aversion or resulted from painful stimulation. Vocalizations in the 22-28 kHz range were measured in male rats during non-aggressive and aggressive social interactions; when given foot shock with a partner; during non-aggressive social interactions after an injection of (i) acetic acid (1%, IP); (ii) pentylenetetrazol (20-30 mg/kg, IP) and (iii) lithium chloride (63.8 mg/kg, IP). Ultrasonic vocalizations were consistantly detected in all rats while the animals displayed defensive or submissive postures when tested as intruders confronted with offensive residents or when administered foot shocks. Only occasional vocalizations were emitted, even in the presence of a partner, when the animals had received other painful or aversive treatments. These data support the hypothesis that 22-28 kHz vocalizations during intermale interactions are associated with defensive postures and are not the consequence of a state of fear or aversion. PMID- 7870952 TI - Effects of ZK 93426 on muscarinic and nicotinic antagonist or nucleus basalis lesioning-induced electrocortical slowing. AB - The present study investigated the effects of a benzodiazepine receptor antagonist, beta-carboline ZK 93426 (1, 3 and 10 mg/kg, IP), on scopolamine and nucleus basalis (NB) quisqualic acid lesion-induced neocortical electrocortical activity slowing in rats. Scopolamine induced a dose dependent increase in EEG spectral values and slow delta waves (0.3 < 0.9 = 2.7 mg/kg IP). ZK 93426 partially reversed EEG slowing induced by the smallest scopolamine dose (0.3 mg/kg), but had no effect on the EEG changes induced by higher doses. A combination of scopolamine at 0.3 mg/kg and mecamylamine (a centrally active nicotinic antagonist) at 10 mg/kg induced an EEG slowing that was not reversed by ZK 93426. NB lesions markedly decreased cortical choline acetyltransferase (ChAT) activity (-77%) and increased EEG slow waves. ZK 93426 had no effect on the NB lesion-induced slow wave activity increase. The present results support the idea that beta-carboline ZK 93426 may increase cortical cholinergic activity by disinhibiting the NB cholinergic neurons. However, if the activity of "NB to cortex" cholinergic system is greatly decreased by either a marked reduction in NB cell number (in NB-lesioned rats), a near complete cortical post-synaptic muscarinic receptor blockade (large scopolamine dose) or by a combination of nicotinic (decrease acetylcholine release) and muscarinic receptor blockade, the effects of beta-carboline ZK 93426 on EEG slowing may be negligible. PMID- 7870953 TI - Self-administration of GBR 12909 on a fixed ratio and progressive ratio schedule in rats. AB - Intravenous self-administration of GBR 12909, an indirect dopamine agonist, was examined on a Fixed Ratio (FR 1) and a Progressive Ratio (PR) schedule of reinforcement in rats. Subjects were first trained to self-administer cocaine (1.5 mg/kg/inj) during daily 5 h sessions, after which GBR 12909 (0.187-1.5 mg/kg/inj) was substituted. On the FR 1 schedule, the inter-infusion interval for GBR 12909 self-administration was directly related to dose and was approximately three times longer than that established for equivalent doses of cocaine. Breaking points on the PR schedule were comparable for GBR 12909 and cocaine self administration. The data indicate that, compared to cocaine, GBR 12909 has a longer duration of action and a similar reinforcing efficacy. PMID- 7870954 TI - Striatal regulation of morphine-induced hyperphagia: an anatomical mapping study. AB - Both systemic and intracranial administration of morphine can result in spontaneous feeding in non-deprived rats. The present investigation was conducted to examine the involvement of the striatum in this phenomenon. Morphine sulfate (0, 0.5, 1.0, 5.0, 10.0, and 20.0 micrograms/0.5 microliters) was microinjected into five discrete striatal subregions in non-deprived rats: the nucleus accumbens, the ventromedial striatum, the ventrolateral striatum, the anterior dorsal striatum, and the posterior dorsal striatum. Feeding, drinking, locomotion, rearing, and food intake were measured over 4 h after infusion. Results indicate that the striatum is a heterogeneous structure with regard to the regulation of opiate-induced feeding behavior and locomotor activity. Morphine infusion into anteroventromedial regions including the nucleus accumbens resulted in a marked hyperphagia that was generally delayed in onset; much smaller increases or no change in feeding occurred after administration into more dorsal, lateral and posterior areas. It is hypothesized that there may exist within the striatum an anatomical gradient that is most sensitive to opiate induced feeding within the anteroventromedial sector. Since this area has extensive connections with other brain sites sensitive to opiate-induced feeding, it may be a critical part of an opiatergic feeding system within the brain. In addition, a possible role for the anteroventromedial striatum in compulsive feeding and bulimia is discussed. PMID- 7870955 TI - Heroin self-administration in rats under a progressive ratio schedule of reinforcement. AB - Heroin self-administration behavior under a progressive ratio (PR) schedule of reinforcement was evaluated in rats. The schedule was designed to restrict drug intake, minimize opiate dependency, and quantify the number of responses emitted (final response ratio) in order to receive a limited number of heroin infusions. Final ratios were found to be stable and did not increase with chronic (31 days) PR reinforcement. The ability of the PR schedule to detect changes in heroin reinforcement was demonstrated by evaluating the effect of naltrexone pretreatment and unit dose alteration on final ratios. Naltrexone (0.4 mg/kg) reduced final ratios and an inverted U dose-response relationship was established for the unit heroin doses 12.5-100 micrograms/injection. Maximal final ratios occurred with 50 micrograms/injection heroin reinforcement. This PR schedule may provide a useful method for evaluating the effects of pharmacological manipulations or lesions on opiate reinforcement. PMID- 7870956 TI - The role of GABAB receptors in mediating the stimulatory effects of ethanol in mice. AB - Recently, the GABAB receptor antagonist phaclofen has been shown to attenuate the stimulation of locomotor activity induced by ethanol (Allan and Harris 1989). In the present study, the effects of a range of recently developed GABAB receptor antagonists (phaclofen, 2-hydroxysaclofen, beta-phenyl-beta-alanine, CGP 35348) and the GABAB receptor agonist baclofen, were studied for their ability to block the locomotor stimulation induced by a low dose of ethanol administered IP to mice (1.75 g/kg). Results showed that phaclofen, 2-hydroxysaclofen, BPBA and baclofen all dose-dependently decreased ethanol-induced locomotor activity, and, of these, baclofen and BPBA did so at doses which did not attenuate locomotor activity when administered alone. CGP 35348 had no effect on the activity produced by ethanol. The action of baclofen on ethanol-induced activity appeared to be GABAB receptor mediated, as the effects were stereospecific and were reversed by the antagonist, CGP 35348. However phaclofen, 2-hydroxysaclofen and BPBA failed to reverse the effects of baclofen. These results suggest that the GABAB receptor may modulate locomotor stimulation induced by low doses of ethanol, and furthermore, that agonist, rather than antagonist activity at the GABAB receptor is responsible for this reduction. The GABAB receptor subtype responsible for modulating the effects of ethanol may have properties different from those GABAB receptors characterised to date. PMID- 7870958 TI - Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on choice between delayed reinforcers. AB - The possible involvement of the ascending 5-hydroxytryptaminergic (5HTergic) pathways in determining the effectiveness of delayed positive reinforcers was investigated using Mazur's (1984) adjusting-delay paradigm. Fourteen rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei; 12 rats received sham lesions. The rats made repeated choices in a two lever operant conditioning chamber between a smaller reinforcer delivered after a 2-s delay and a larger reinforcer delivered after a variable delay, the length of which was determined by the subject's previous choices. When the two reinforcers consisted of one and two food pellets, the "indifference point" (the delay to the larger reinforcer that rendered the two reinforcers equally effective) was shorter in the lesioned group than in the control group. Increasing the sizes of the reinforcers to three and six pellets reduced the indifference point in both groups and abolished the between-group difference. The levels of 5HT and 5 hydroxyindoleacetic acid (5HIAA) in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were greatly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected. The results are consistent with the suggestion that the 5HTergic pathways play a role in maintaining the effectiveness of delayed reinforcers. PMID- 7870957 TI - Behavioral effects of selective and nonselective dopamine agonists on young rats after irreversible antagonism of D1 and/or D2 receptors. AB - In general, preweanling and adult rats respond similarly when challenged with competitive dopamine (DA) agonists or antagonists. In contrast, results using a noncompetitive antagonist suggest that the D1 and D2 receptor systems of preweanling and adult rats differ in some critical way. To further assess this phenomenon, the behavioral effects of irreversible receptor blockade were assessed across 8 days in NPA (a nonselective DA agonist), quinpirole (a D2 agonist), or SKF 38393 (a D1 agonist) treated 17-day-old rat pups. The irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) did not block the locomotor activity and rearing of NPA- or quinpirole-treated rat pups, nor did EEDQ reduce SKF 38393-induced grooming. Moreover, pretreatment with EEDQ appeared to potentiate the normal increases in locomotor activity and rearing produced by NPA, but only when D2 receptors were not protected by a previous injection of sulpiride (a D2 antagonist). Taken together, these results are consistent with the presence of large reserves of D1 and D2 receptors in the preweanling rat pup. PMID- 7870959 TI - A behavioural and pharmacological evaluation of the discriminative stimulus induced by pentylenetetrazole in the pig. AB - The anxiogenic nature of the interoceptive discriminative stimulus induced by pentylenetetrazole (PTZ) was investigated by examining the discriminatory behaviour of PTZ conditioned pigs during a conditioned emotional response (CER). A CER was induced in a nonoperant situation, by pairing a tone stimulus with the application of a mild, non-injurious electric shock. Subsequent presentation of the conditioned tone stimulus alone produced a generalisation to the PTZ cue. This generalisation of the conditioned emotional state (CES) to the PTZ cue was antagonised by pretreatment with diazepam (0.5 mg/kg, PO; 30 min). The PTZ stimulus was also antagonised by diazepam (0.5 mg/kg, PO; 30 min) but not by an anticonvulsant dose of ethosuximide (30 mg/kg, PO; 1-3 h), providing further confirmation of the anxiogenic nature of the PTZ cue. Our results demonstrate the validity of the PTZ discrimination paradigm in pigs as a test of anxiety. PMID- 7870960 TI - The catalepsy of blocked dopaminergic receptors. PMID- 7870961 TI - Chlormethiazole attenuates the derangement of sensory evoked potential (SEP) induced by ICV administration of NMDA. AB - Administration to anaesthetized rats of N-methyl-D-aspartate (NMDA 30 nmol ICV) induced a profound derangement of stimulation evoked potential (f-SEP) and also autonomic excitation with an increase in arterial blood pressure and heart rate. These effects were antagonised by pretreatment with dizocilpine (0.5 mg/kg IV). Pretreatment with chlormethiazole (20 mg/kg IV 26 min before NMDA) also markedly diminished the derangement of f-SEP. At the end of the registration period 2 h after NMDA the SEP had recovered to 72.7 +/- 3.4 (% of control; mean +/- SEM) in saline-treated rats as compared to 96.1 +/- 5.6% in chlormethiazole treated animals (P < 0.01). In contrast to dizocilpine, chlormethiazole alone had no effect on heart rate or blood pressure and did not alter the autonomic effects of ICV NMDA. These results demonstrate that chlormethiazole can antagonise some NMDA receptor mediated functions, even though there is no evidence that it is an NMDA antagonist. PMID- 7870963 TI - Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms. AB - Nicotine gum and transdermal nicotine have been shown to relieve withdrawal and double success rates over placebo in trials of smoking cessation. This study tested whether combining the two methods would relieve withdrawal more effectively compared to either treatment alone. Twenty-eight smokers served as their own controls in each of four conditions: active gum + active patch (double active), active gum + placebo patch (gum only active), placebo gum + active patch (patch active) and placebo gum + placebo patch (double placebo). This "double placebo" design controls sensory, psychological and ritual variables associated with each drug form. Withdrawal symptoms were rated four times daily for 3 days in each condition. Total baseline (smoking) withdrawal scores using visual analogue scales (VAS) averaged 101.1. During cessation, total withdrawal increased to 187.0 for the double placebo condition, 142.2 for the active gum/placebo patch treatment and 128.3 for the active patch/placebo gum treatment. The double active condition equalled smoking with score 99.2. All pairwise comparisons were significant (P < 0.001) except between the two single active conditions and between smoking versus the double active condition. Significant time-of-day effects by treatment on withdrawal were observed for the double placebo condition (P < 0.05) with less withdrawal in the morning. The findings suggest: 1) combining nicotine gum with transdermal nicotine may be superior to either treatment alone, 2) more symptoms may be nicotine specific (relieved by replacement) than previously thought. PMID- 7870962 TI - Drug discrimination by humans compared to nonhumans: current status and future directions. AB - In drug discrimination (DD) procedures, behavior is differentially reinforced depending on the presence or absence of specific drug stimuli. The DD paradigm has been widely adopted by behavioral pharmacologists because of its specificity of stimulus control, concordance with drug action at cellular levels and its use as a preclinical model of subject-rated effects in humans. With the successful extension of DD to humans, a comparison of human and nonhuman DD will help place each in the context of the other. Twenty-eight studies of DD in humans are reviewed, including studies of amphetamine, opioid, benzodiazepine, caffeine, nicotine, marijuana and ethanol discriminative stimuli. Comparison of procedures between studies in humans and nonhumans reveals a common tradition, except the use of instructions appears to facilitate greatly DD acquisition in humans. Findings were qualitatively similar between humans and nonhumans. Potency relationships were quantitatively similar between humans and most, but not all, other species. Areas of human DD needing additional empirical evaluation include the influence of instructions, the effects of training dose and the effects of antagonists. Additionally, antihistamines, barbiturates, nicotine and marijuana are under-represented in human DD. PMID- 7870964 TI - Assessment of tardive dyskinesia by means of digital image processing. AB - A wireless device for the assessment of tardive dyskinesia by means of digital image processing is presented. Four skin-cream dots placed around the subjects' mouth are recorded by a video camera. The image is passed to a framegrabber with a signal processor, where it is converted from analogue to digital. A fast spot detecting algorithm implemented on the signal processor tracks the dots and passes the information to a personal computer where a Fourier transformation is performed to calculate the frequency spectrum of the movements. The device provided detailed information on the magnitude and on the frequencies of the movements. Data from a longitudinal investigation suggest a higher sensitivity and reliability than conventional rating scales to detect and evaluate abnormal perioral movements. The device might be useful for the early detection, for the longitudinal assessment (p.e. clinical trials) and in some cases for the differential diagnosis of tardive dyskinesia, thus providing a tool for both research and clinical purposes. PMID- 7870965 TI - Acute behavioral and cardiac effects of cocaine and alcohol combinations in humans. AB - Subjects received acute doses of orally administered alcohol (0-1.0 g/kg) and intranasal cocaine (4-96 mg/70 kg) alone and in combination in two experiments. Results generally were consistent across both experiments. Cocaine administered alone improved Digit Symbol Substitution Test (DSST) performance, increased subject ratings of stimulant-like effects, heart rate and blood pressure, and decreased skin temperature. Alcohol administered alone disrupted DSST performance, increased ratings of drunkenness, heart rate and skin temperature, and decreased blood pressure. Combining cocaine and alcohol attenuated the disruptions in DSST performance observed with alcohol alone, and either did not change or attenuated the improvements in performance observed with cocaine alone. Combining the drugs also attenuated effects observed with the drugs alone on skin temperature and, to a lesser extent, blood pressure. By contrast, drug combinations increased heart rate above levels observed when cocaine or alcohol were administered alone. Effects of the drug combinations on subject ratings were variable. PMID- 7870966 TI - Dose-dependent effects of intravenous alprazolam on neuroendocrine, biochemical, cardiovascular, and behavioral parameters in humans. AB - Neuroendocrine, biochemical, cardiovascular, and behavioral parameters were assessed in seven normal volunteers for 2 h after intravenous administration of alprazolam (APZ). Three doses of APZ (0.003, 0.007, and 0.02 mg/kg) were administered to each subject in a random order with at least 4 days between infusions. Plasma growth hormone and sedation increased in a dose dependent manner after APZ, and there was a dose dependent change in the shape of the cortisol response to APZ. No dose-response relationships were evident for plasma ACTH and norepinephrine. These differences in dose-response relationships may reflect the involvement of multiple systems in controlling neuroendocrine, biochemical, and subjective responses to APZ infusion. The optimal dose of APZ needed to produce a neuroendocrine or behavioral change appears to differ depending on the parameter of interest. PMID- 7870967 TI - Are patterns of benzodiazepine use predictable? A follow-up study of benzodiazepine users. AB - A sample of 171 patients taking benzodiazepines (BZDs) who had been investigated in 1988 was followed up in 1991. From 140 patients who were still alive and willing to participate, 25% had stopped BZDs after an average duration of intake of 34 months. Of the 105 persons still taking a BZD, 37% were taking the same dose, 26% had reduced the dose and 37% had increased it. Characteristics of BZD long-term users and patients potentially at risk for abuse and/or dependence that were established from the 1988 data were reexamined: patients with continued BZD use more often suffered from somatic illness which often had deteriorated, they had a longer duration of intake and used higher daily doses. In most cases the indication was insomnia. Patients with a clinically relevant dose increase were more often males, frequently found to be dependent on alcohol and/or illegal drugs. PMID- 7870968 TI - Subjective, behavioral and physiological responses to intravenous meperidine in healthy volunteers. AB - Meperidine is a mu opiate agonist that is frequently used to treat pain. We examined in healthy volunteers (N = 10) the effects of intravenous meperidine (0, 0.25, 0.5, and 1.0 mg/kg) on mood and psychomotor performance. A randomized, placebo-controlled, crossover design was used in which subjects were injected with meperidine or saline in a double-blind fashion. Subjects completed several subjective effects questionnaires commonly used in abuse liability testing studies before drug injection and at periodic intervals for up to 5 h after drug injection. Subjects also completed several psychomotor tests. Meperidine produced a constellation of subjective effects in a dose-related fashion, including increases in ratings of "sedated," "coasting or spaced out" and "feel drug effect" ratings. Many of the drug's subjective effects persisted up to 4 or 5 h after administration of the 1.0 mg/kg dose. Drug liking ratings assessed on a visual analog scale were increased after meperidine injection in about half of the subjects (P = 0.09). Eye-hand coordination was affected slightly by meperidine but other indices of psychomotor functioning were unaffected. Miosis increased in a dose-related fashion. Other physiological parameters, such as vital signs, were not affected by meperidine. We conclude that meperidine in healthy volunteers has robust and long-lasting effects on mood, but may have weaker effects on psychomotor performance. PMID- 7870969 TI - Discriminative stimulus effects of omega (BZ) receptor ligands: correlation with in vivo inhibition of [3H]-flumazenil binding in different regions of the rat central nervous system. AB - Rats can be trained to discriminate benzodiazepines (BZ) from vehicle and there is considerable evidence that the stimulus effects of these drugs are mediated by activity at omega (BZ) modulatory sites of the GABAA receptor complex. A number of recent studies, however, have indicated that differences may exist between the discriminative stimulus effects of benzodiazepines and those of certain non benzodiazepine ligands for the omega (BZ) receptors (e.g. zolpidem, abecarnil). As it is known that several subtypes of omega (BZ) sites are found in the central nervous system, and that drugs such as zolpidem have selectivity for certain subtypes, it is possible that differential stimulus effects may be associated with receptor selectivity. In the present study, correlations were calculated between the potencies of nine compounds with affinity for omega receptors (diazepam, lorazepam, triazolam, clonazepam, alprazolam, zopiclone, suriclone, CL 218, 872 and zolpidem) to substitute for chlordiazepoxide in rats trained to discriminate a dose (5 mg/kg) of this benzodiazepine and the ability of the same compounds to inhibit the binding of [3H]-flumazenil from different structures in the rat central nervous system in vivo. The correlations obtained were: cerebellum 0.46, cortex 0.39, striatum 0.78 (P < 0.05), hippocampus 0.79 (P < 0.05) and spinal cord 0.95 (P < 0.001). These different structures are known to contain different relative concentrations of omega 1 (BZ1) and omega 2 (BZ2) sites with the spinal cord containing the greatest (80%) and cerebellum the lowest (5%) concentration of omega 2 (BZ2) sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870970 TI - Differences in fear motivated behaviors among inbred mouse strains. AB - The behavioral performance of inbred mouse strains was examined in animal models of anxiety to evaluate the potential contribution of genetic factors to fear motivated behaviors. The preference that randomly bred mice and rats exhibit for the enclosed as opposed to the open arms of an elevated maze has been considered a fear-motivated behavior. Pronounced differences were observed in this measure among 16 inbred mouse strains. An estimate of the proportion of the variance attributable to between-strain differences, eta 2, revealed that 78% and 69% of the variance in time and number of entries in the open arms of an elevated maze, respectively, can be attributed to genetic factors. In contrast, only 27% and 42% of the variance could be attributed to between-strain differences in ambulatory activity in the open field and elevated maze, respectively. Furthermore, performance in the elevated maze was predictive of behavior in other animal models of anxiety. Thus, significant negative correlations were observed among inbred mouse strains between the percent time spent in the open arms of the elevated maze and amplitude of an acoustic startle response (rs = -0.88m P < 0.01) or latency to initiate chow consumption in a hyponeophagia paradigm (rs = 0.71, P < 0.05). These results indicate that genetic factors substantially contribute to fear motivated behaviors in these animal models of anxiety. The use of such inbred mouse strains may provide a novel approach to investigate the biochemical and genetic bases of fear. PMID- 7870971 TI - Development and expression of sensitization to cocaine's reinforcing properties: role of NMDA receptors. AB - Acquisition of cocaine self-administration (0.125, 0.25 or 0.5 mg/kg/infusion) was assessed in rats that had received prior exposure to either saline or amphetamine (2.0 mg/kg). Acquisition of self-administration was dose-dependent, with the highest dose leading to the shortest latency to reliably discriminate between depression of a lever that resulted in drug delivery and an inactive lever. Latency to acquisition of the lever discrimination for rats that had received prior exposure to amphetamine was shorter than for the saline-pretreated counterparts in each cocaine dosage group. This suggests that repeated exposure to this drug prior to self-administration testing sensitized the rats to the reinforcing effects of cocaine. Co-administration of MK-801 (0.25 mg/kg, IP), a non-competitive NMDA antagonist, blocked the ability of chronic exposure to amphetamine to sensitize rats to cocaine. In experienced self-administering rats, acute pretreatment with MK-801 resulted in a loss of discriminative responding. The number of inactive lever responses was consistently higher than the number of active lever responses across all cocaine dosage groups. These data suggest that the NMDA receptor, possibly through interactions with dopamine systems, is critical for both the development and expression of sensitization to cocaine's reinforcing effects produced by intermittent preexposures to amphetamine. PMID- 7870972 TI - The effects of haloperidol and clozapine on the disruption of sensorimotor gating induced by the noncompetitive glutamate antagonist MK-801. AB - The amplitude of the acoustic startle response in rats is decreased if the startle stimulus is preceded by a nonstartle-eliciting auditory stimulus. This sensory gating phenomenon, known as prepulse inhibition, is diminished in schizophrenic individuals. In rats, the noncompetitive glutamate antagonist MK 801 disrupts prepulse inhibition. The present study examined whether the disruption by MK-801 is reversible in rats pretreated with the classical antipsychotic haloperiodol or the atypical antipsychotic clozapine. Male Sprague Dawley rats were placed into a startle chamber and presented with auditory stimuli consisting of either 95 or 105 dB tones presented alone or preceded by a 70 dB tone. Rats treated with 0.1 mg/kg MK-801 demonstrated a significant disruption of prepulse inhibition. Haloperidol (0.1 and 0.5 mg/kg) and clozapine (1.0 and 5.0 mg/kg) each consistently failed to antagonize the MK-801-induced blockade of prepulse inhibition. The effects of haloperidol and clozapine on prepulse inhibition were also examined in saline-treated rats. Clozapine and, to some extent, haloperidol produced a dose-related facilitation of prepulse inhibition. Although preliminary, this finding raises the possibility that the enhancement of prepulse inhibition by antipsychotics might provide a useful rodent model for screening potential antipsychotic drugs. PMID- 7870973 TI - Norbinaltorphimine blocks the feeding but not the reinforcing effect of lateral hypothalamic electrical stimulation. AB - The role of central kappa opioid receptors in the regulation of feeding and reward was evaluated using electrical brain stimulation paradigms in combination with the selective kappa antagonist, norbinaltorphimine (nor-BNI). Lateral ventricular injection of 10.0 and 50.0 nmol doses of nor-BNI increased the lateral hypothalamic stimulation frequency threshold for eliciting feeding behavior but had no effect on threshold for self-stimulation in the absence of food. This result is identical to those previously reported for naloxone and antibodies to dynorphin A and suggests that opioid activity is associated with feeding behavior rather than the eliciting brain stimulation. A further similarity between naloxone, dynorphin antiserum, and nor-BNI is their preferential effect on feeding threshold values obtained later, rather than initially, in a post-injection test session. This pattern of threshold elevation is shown to differ from that of the appetite suppressants, amphetamine and phenylpropanolamine, which elevate threshold uniformly throughout a post injection test. The signature pattern of threshold elevation produced by opioid antagonism is consistent with the hypothesis that opioid activity is involved in the maintenance rather than the initiation of feeding. Specifically, it is hypothesized that a dynorphin A/kappa receptor mechanism is triggered by food taste and sustains feeding behavior by facilitating incentive reward. PMID- 7870974 TI - Altered spontaneous behavior and sensitivity to apomorphine in rats following pretreatment with S(+)-aporphines or fluphenazine. AB - Rats were pretreated for 2 weeks with similarly effective doses of the typical neuroleptic fluphenazine (FPZ) or the experimental weak partial D2 agonists S(+)N n-propylnorapomorphine (NPA) and S(+)11-hydroxy-N-n-propylnoraporphine (11-OH NPa). Spontaneous and dopamine (DA) agonist (apomorphine; APO) stimulated stereotyped behaviors or locomotion, and interactions with APO were evaluated over the following 2 weeks. While FPZ induced marked supersensitivity in APO stereotype, (+)NPA showed no significant change, and (+)11-OH-NPa produced only a small, transient increase in response; NPA also lacked a supersensitizing effect on locomotor arousal induced by APO. The time-course of stereotyped responses to APO following pretreatment with FLZ included a marked increase following FPZ that became maximal at day 5 and normalized by day 9; there was a parallel reduction of acute antisteotypy efficacy of FPZ. (+)11-OH-NPa had similar, but much lesser and shorter-lived effects. Spontaneous locomotion was markedly depressed following FPZ, recovered in 1 week, exceeded controls at day 9, and returned to baseline by day 11; (+)11-OH-NPa, again, had similar but smaller effects. Acute effects of FPZ to reduce spontaneous or APO-induced locomotion were greater after FPZ pretreatment and normalized within a week; (+)11-OH-NPa had a similar but smaller effect. Locomotor arousal by APO was altered inconsistently in the week after pretreatment with FPZ or (+)11-OH-NPa. Thus, FPZ appeared to induce tolerance and supersensitivity in central DA systems, most clearly seen following a several-day period to eliminate the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870975 TI - Addition of lithium to haloperidol in non-affective, antipsychotic non-responsive schizophrenia: a double blind, placebo controlled, parallel design clinical trial. AB - This double-blind placebo controlled, parallel design clinical trial compared the therapeutic effects of the addition of lithium or placebo to haloperidol in 21 seriously ill state hospital patients with DSM-III-R schizophrenia, who did not have concurrent affective disorders and who had not responded to previous trials of conventional antipsychotic medication. During a baseline period of 6 weeks, patients were switched to a stable dose of haloperidol (mean +/- SD dose = 13.6 +/- 8.1 mg/day). Patients were then randomized to receive either lithium or placebo in addition to haloperidol for 8 weeks (mean +/- SD lithium level = 0.98 +/- 0.13 mEq/l). Symptoms and side effects were assessed weekly. Improvement in symptoms correlated with the non-blind adjustment of antipsychotic dose, but not with lithium or placebo treatment. Side effects ratings did not differ between the two groups, but one patient developed a reversible delirium associated with combined lithium/haloperidol treatment. For these long-term, severely ill patients, combined treatment afforded no advantage over treatment with haloperidol alone. PMID- 7870976 TI - Morphine attenuates ultrasonic vocalization during agonistic encounters in adult male rats. AB - Ultrasonic vocalizations (USV) in rats may communicate "affective" states during pain, sex and aggression. This proposal was evaluated in an experiment with adult male Long-Evans rats during agonistic encounters; specifically, morphine and naltrexone effects were studied on different types of USV by intruder rats exposed to resident attacks and to "threat of attacks" (i.e., intruder residing within the home cage of the resident but prevented from physical contact by a wire mesh cage). Intruders readily emitted USV during agonistic encounters. These calls consisted primarily of two distinct distributions of pure tone whistles: 0.3-3 s, 19-32 kHz ("low") calls and 0.02-0.3 s, 32-64 kHz ("high") calls. Sonographic analysis revealed a considerable repertoire of frequency modulated calls. Different types of vocalizations proved to be differentially sensitive to the opiate treatments: morphine (1-10 mg/kg SC) dose-dependently decreased the rate, duration and pitch of both low and high frequency USV during the threat of attack; this decrease in rate and duration measures was naltrexone-reversible (0.1 mg/kg IP). Interestingly, audible vocalizations were also emitted but were unaffected by morphine in this dose range. Concomitant with the decrease in USV after morphine was a dose-dependent decrease in rearing, walking and nasal contact behavior with increases in submissive crouch behavior and tail flick analgesia. The decreases in rate and duration of both low and high USV and the pitch of specific frequency modulated calls after morphine administration may reflect an attenuation of affective aspects of pain, and the many characteristics of US (rate, duration, pitch, frequency modulation, pre-and suffix attributes and temporal structure) point to potentially diverse functions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870977 TI - Influence of histamine depletion on learning and memory recollection in rats. AB - To clarify the role of endogenous histamine in learning and memory, the effect of alpha-fluoromethylhistidine on active avoidance response in rats was studied. alpha-Fluoromethylhistidine (20-100 mg/kg or 10-50 micrograms) significantly (P < 0.05 or P < 0.01) prolonged the response latency in active avoidance response when administered by either intraperitoneal or intracerebroventricular injection. These effects were dose-related and long lasting. A prolongation of the response latency induced by an intraperitoneal injection of alpha-fluoromethylhistidine (100 mg/kg) was antagonized by intracerebroventricular injection of histamine (10 and 20 ng) in a dose-dependent manner. In addition, the acquisition of this response was retarded by a consecutive intracerebroventricular injection of alpha fluoromethylhistidine (50 micrograms), whereas histamine (100 ng) facilitated the response acquisition when administered by the same route. Both intraperitoneal (100 mg/kg) and intracerebroventricular injection of alpha-fluoromethylhistidine (50 micrograms) significantly (P < 0.05 or P < 0.01) decreased the brain histamine content, especially in the hippocampus and hypothalamus. When alpha fluoromethylhistidine (50 micrograms) was injected intracerebroventricularly, there is a high correlation between a prolongation of the response latency and a decrease in histamine content of these brain areas. Based on these findings, it was concluded that an intimate relation may exist between a prolongation of response latency in the active avoidance response and a decrease in the brain histamine content; endogenous histamine may play an important role in learning and memory recollection in rats. PMID- 7870978 TI - Adenosine A2 receptor regulation of apomorphine-induced turning in rats with unilateral striatal dopamine denervation. AB - The ipsilateral intrastriatal administration of the specific adenosine A2a receptor agonist, 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS 21680), produced a dose related decrease in apomorphine-induced rotation in the unilaterally 6-hydroxydopamine-lesioned rat. This effect could be reversed by intrastriatal infusions of the A2a antagonist, 4-amino-1 phenyl[1,2,4]triazolo[4,3-a]quinoxaline (CP 66,713). However, CP 66,713 had no significant effect when infused alone, neither did it influence the response to apomorphine in the absence of CGS 21680. The possible behavioural interactions between A2a receptors and striatal ACh activity were also investigated using this model. Atropine administered intrastriatally in a dose that had no effect on the response to apomorphine reduced the inhibitory effects of CGS 21680 on apomorphine-induced turning. Naloxone also reduced the effects of apomorphine, an effect which could be prevented by the co-administration of atropine, or CP 66,713. These results indicate that adenosine agonists can modulate apomorphine induced turning by an interaction with both cholinergic and opioidergic mechanisms in the striatum. PMID- 7870979 TI - Glutamate: its role in learning, memory, and the aging brain. AB - L-Glutamate is the most abundant of a group of endogenous amino acids in the mammalian central nervous system which presumably function as excitatory neurotransmitters and under abnormal conditions may behave as neurotoxins. As neurotransmitters, these compounds are thought to play an important role in functions of learning and memory. As neurotoxins, they are believed to be involved in the pathogenesis of a variety of neurodegenerative disorders in which cognition is impaired. Moreover, brain structures which are considered anatomical substrata for learning and memory may be particularly vulnerable to the neurotoxic actions of these excitatory amino acids, especially in the elderly who are also the segment of the population most susceptible to impairments of mnemonic function. This paper is a review of data concerning the role of excitatory amino acids in the processes of learning and memory and in the pathogenesis and treatment of disorders thereof. PMID- 7870980 TI - Phencyclidine-induced potentiation of brain stimulation reward: acute effects are not altered by repeated administration. AB - Phencyclidine (PCP; 2.5 or 5.0 mg/kg) potentiated the effects of rewarding hypothalamic brain stimulation, causing parallel leftward shifts of the functions that relate rate of responding to stimulation frequency. Thus, like a number of other drugs of abuse, PCP lowered the "dose" of stimulation required to maintain responding at a given criterion. No progressive changes in the reward potentiating effects of PCP were evident when the rats were tested once per week for 8 weeks; there was neither tolerance nor sensitization to the initial rewarding properties of PCP. However, in subsequent locomotor tests rats appeared to be already sensitized to PCP; this raises the possibility that the electrical stimulation of the lateral hypothalamus itself maximally sensitized the animals to the stimulant effects of the drug. PMID- 7870981 TI - Oral etonitazene and cocaine consumption by AA, ANA and Wistar rats. AB - It has been previously suggested that drug-seeking behavior maintained by alcohol, opioids, and cocaine may have some common genetic determinants. Therefore, the present study examined the intake of etonitazene, a potent opioid agonist, and cocaine by alcohol-preferring AA (Alko, Alcohol), alcohol-avoiding ANA (Alko, Non-alcohol), and Wistar rats in a two-bottle choice test. The animals, housed in single cages, were given a choice between tap water and ascending concentrations of etonitazene (0.5, 1.0, 2.0, and 4.0 micrograms/ml) or cocaine (0.2, 0.4, 0.8, and 1.6 mg/ml) solutions prepared in water. Finally, to assess the sensitivity to bitter taste by these strains, a quinine preference test with ascending quinine concentrations was conducted. The clearest line differences were found with etonitazene: at all concentrations, the AAs consumed significantly more etonitazene than the ANAs and Wistars that showed no differences. The highest etonitazene intake by the AAs, 181 micrograms/kg/day at the concentration of 4.0 micrograms/kg, produced apparent signs of opioid intoxication and withdrawal. The AAs also drank more cocaine solution than the other lines. Since, however, the pattern of cocaine intake as a function of concentration resembled that with quinine, the line differences in cocaine consumption may partly be accounted for by the differential sensitivity to bitter taste by the lines. In contrast, the marked line differences in the intake of the etonitazene solutions, which had only a slightly bitter taste, seem more likely to have been produced by the post-ingestional effects of the opioid. PMID- 7870982 TI - Pharmacological characterization of benzodiazepine receptor ligands with intrinsic efficacies ranging from high to zero. AB - Several benzodiazepine receptor ligands were pharmacologically characterized in a battery of functional tests after oral administration in mice, rats, and monkeys. Previous experiments have consistently demonstrated that diazepam exhibits high intrinsic efficacy, bretazenil exhibits intermediate intrinsic efficacy, Ro 42 8773 and Ro 41-7812 both show low intrinsic efficacy, and flumazenil exhibits virtually zero intrinsic efficacy. In the test battery used here it appears that nearly full intrinsic efficacy is required for clear anterograde amnesia or rotarod impairment. In contrast, full protection in the pentetetrazol test was achieved with intermediate-to-high intrinsic efficacy and nearly full protection with lower intrinsic efficacy. In the audiogenic seizure test full anticonvulsant effects were produced with intrinsic efficacy ranging from low to high. Clear inhibition of punished operant responding was observed for all test compounds except for Ro 41-7812 and flumazenil, which exhibit the lowest intrinsic efficacies. All of the test compounds enhanced palatable food consumption, with even those having low intrinsic efficacy producing maximum effects approximating that of diazepam. By additionally taking into consideration the degree of receptor occupancy required to obtain pharmacological activity in each of the tests in this battery it is possible to order the compounds with respect to intrinsic efficacy: diazepam > bretazenil > Ro 42-8773 > Ro 41-7812 > flumazenil. The latter four compounds all exhibited a maximum antagonistic activity in tests involving reversal of meclonazepam- or flunitrazepam-induced central nervous system depression. Thus, using these tests appears to permit the accurate ordinal classification of benzodiazepine receptor ligands for intrinsic efficacy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870983 TI - Involvement of delta-opioid receptors in the effects of morphine on locomotor activity and the mesolimbic dopaminergic system in mice. AB - Naltrindole (NTI) and naltriben (NTB), a benzofuran derivative of NTI, were recently synthesized as highly selective delta-opioid receptor antagonists. Both NTI and NTB failed to suppress the antinociceptive effect induced by morphine. In contrast, both NTI and NTB significantly suppressed the morphine-induced hyperlocomotion and increase in turnover of dopamine (DA) in the mouse limbic forebrain. These results suggest that delta-opioid receptors play, at least in part, a role in the morphine-induced hyperlocomotion and excitation of mesolimbic DA systems, but not antinociception. PMID- 7870984 TI - Effects of dopamine D1 and D2 receptor blockade on MK-801-induced hyperlocomotion in rats. AB - Blocking glutamatergic transmission at the N-methyl-D-aspartate (NMDA) receptor complex with MK-801 (0.15-0.5 mg/kg, IP) was found to induce a robust, dose dependent increase in locomotor activity. This behavioural activation was similar in intensity to that observed after d-amphetamine (1 mg/kg, SC). The locomotor stimulation induced by MK-801 at 0.3 mg/kg was significantly inhibited by the D2 dopamine receptor antagonist raclopride (0.1-0.3 mg/kg, SC) and by the D1 receptor antagonist SCH 23390 (0.04 mg/kg, SC). The locomotor activity induced by a higher dose of MK-801 (0.5 mg/kg) was reduced by higher doses of raclopride or SCH 23390 administered alone (0.3 and 0.08 mg/kg, respectively), and was inhibited by simultaneous administration of ineffective doses. Raclopride significantly reduced d-amphetamine-induced locomotor activity at a dose (0.2 mg/kg) that also blocked the effects of a low dose of MK-801. In contrast, SCH 23390 blocked the effects of d-amphetamine at a dose (i.e. 0.01 mg/kg) lower than that needed to block MK-801. These results suggest that the dopaminergic system may in part mediate the locomotor effects induced by the NMDA antagonist, MK-801, in rats. However, the locomotor activity induced by MK-801 appears to be less sensitive to dopaminergic receptor blockade than that induced by d-amphetamine, suggesting that the underlying mechanisms, although similar, are not identical. PMID- 7870986 TI - Physical dependence on nicotine gum: effect of duration of use. AB - This study examined whether longer duration on nicotine gum promoted dependence on nicotine gum. Subjects (N = 128) answering an advertisement for smoking cessation research and wanting to quit smoking cigarettes were randomly assigned to 1- or 3-month duration of nicotine gum use. Assessments were made weekly for smoking status (with biochemical verification) and withdrawal symptoms during and at the end of treatment. Follow-up was conducted at 1, 6 and 12 months to provide exploratory data on treatment outcome. The results showed minimal nicotine gum withdrawal symptoms after gum cessation with virtually no difference in gum withdrawal between the 1- and 3-month groups. Withdrawal symptoms from the nicotine gum included difficulty with concentration, increased variability on a reaction time task, and decreased vigor. The results also showed that continuous use of the gum at 1 year was observed in 1.5% of subjects and estimated to be as high as 14%. Finally, the 3-month group experienced a 2-fold increase in abstinence compared to the 1-month group, although this difference was not statistically significant. We conclude that there is minimal physical dependence on nicotine gum. PMID- 7870985 TI - Attenuation of scopolamine-induced spatial memory deficits in the rat by cholinomimetic and non-cholinomimetic drugs using a novel task in the 12-arm radial maze. AB - The effects of cholinomimetic and non-cholinomimetic agents on spatial memory using a novel task in the 12-arm radial maze were investigated. The task was designed to reduce the tendency to use non-spatial strategies. Animals were repeatedly trained to retrieve food rewards from three arms, until a criterion level of performance was reached. Scopolamine (0.03 and 0.1 mg/kg SC), but not N methylscopolamine (0.1 mg/kg SC) disrupted performance of this task. Physostigmine (0.3 mg/kg SC) and pilocarpine (30 mg/kg SC) completely reversed the deficit of performance produced by scopolamine. Furthermore, the ACE inhibitor Hoe 288 (10 nmol ICV) and the angiotensin AT1 receptor antagonist losartan (10 mg/kg SC) also significantly attenuated the scopolamine-induced deficit. These results show that this novel task in the radial maze is sensitive to the disruptive effects of scopolamine and can identify cognitive enhancing effects of both cholinomimetic and non-cholinomimetic drugs. Thus, this maze task provides a useful model for the evaluation of novel cognitive enhancing agents. PMID- 7870987 TI - Reduction of morphine dependence and potentiation of analgesia by chronic co administration of nifedipine. AB - Nifedipine, 5 mg/kg IP, potentiated the morphine-induced analgesia measured in the hot-plate, but not in the tail-flick test. Further experiments were carried out using the hot-plate test only. Pretreatment with nifedipine partially restores the analgesic action of morphine in morphine-tolerant rats. Co administration of nifedipine with morphine in a chronic experiment did not prevent the loss of morphine efficiency (an increase in latency of 44% was not significant) and did not prevent the debilitating effect of chronic morphine administration reflected by an inhibition of the body weight gain, but prevented naloxone-induced withdrawal syndrome (quantified by counting head shakes) in the test carried out 24 h after the injection of nifedipine, when the drug did not affect morphine analgesia. Chronic treatment with either morphine or nifedipine did not produce a significant increase in the density of [3H] naloxone or [3H]prazosin binding sites in the cortex and in the rest of the brain (measured 24 h after the last dose), but the combined treatment resulted in a significant increase in the cortical [3H]prazosin binding site density. The present results suggest that opiate tolerance and physical dependence may be separated by co administration of nifedipine and suggest that the combined chronic treatment with morphine and nifedipine may increase the efficacy of morphine during chronic treatment and prevent development of abstinence. PMID- 7870988 TI - Contrasting effects of the competitive NMDA antagonist CPP and the non competitive NMDA antagonist MK 801 on performance of an operant delayed matching to position task in rats. AB - The effects of the competitive NMDA antagonist CPP and the non-competitive NMDA antagonist MK 801 (dizolcipine) on short term working memory in the rat were investigated. The behavioural paradigm used was discrete trial, operant delayed matching to position, as originally described by Dunnett (1985), with delays of 0, 5, 15 and 30 s. These delays generated an orderly "forgetting" curve in control rats, with matching accuracy decreasing from approximately 100% at 0-s delay to approximately 75% at 30-s delay. Intraperitoneal (IP) administration of CPP (10 mg/kg) produced a marked delay dependent impairment in performance, suggesting a specific effect on short term working memory. This effect was accompanied by a minor decrease in the speed of responding, and a slight increase in the number of missed trials. Lower doses of CPP had no significant effects on either matching accuracy or sedation. In contrast, IP administration of MK 801 (0.1 and 0.2 mg/kg) caused a marked delay independent impairment in the accuracy of delayed matching performance, suggesting a non-specific disruption of performance. A lower dose (0.05 mg/kg) of MK 801 had no significant effect on matching accuracy. The two lower doses of MK 801 increased the number of nose pokes made during the delays and tended to increase the speed of responding, suggesting a stimulant-like action. The highest dose of MK 801 had the opposite effects and also decreased the number of trials completed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870989 TI - Effects of smoking on thermal pain threshold in deprived and minimally-deprived habitual smokers. AB - This study examined the antinociceptive effects of smoking in nine habitual smokers under deprived (12 h) and minimally-deprived (< 30 min) conditions. Pain threshold for thermal stimuli, heart rate, blood pressure and ratings of mood, arousal, dominance and well-being were assessed before and after smoking a cigarette. Over-all, smoking affected all measured variables in the expected direction, leading to increased physiological activity, elevated pain threshold and improved mood. However, most of these effects depended on the deprivation status of the subjects, such that smoking after deprivation increased pain threshold whereas smoking after minimal deprivation did not. Pain threshold before smoking was the same for both groups. Deprived subjects had lower pre smoke diastolic blood pressure, heart rate, and arousal levels, which rose to equal minimally-deprived subjects' scores after smoking. PMID- 7870990 TI - Immobilization stress-induced oral opioid self-administration and withdrawal in rats: role of conditioning factors and the effect of stress on "relapse" to opioid drugs. AB - The effect of 15 min/day of immobilization (IM) stress on oral self administration (SA) of morphine (0.5 mg/ml) or fentanyl (25 micrograms/ml) and withdrawal was examined in rats. In addition, the role of conditioning factors in these effects was assessed. For each drug, four groups of subjects were exposed for 50 days to IM stress prior to the drug SA period [Paired-Stress (P-S) groups], to IM stress prior to the drug SA period on half of the days and after the drug SA period on the rest of the days [Partial Paired-Stress (PP-S) groups], to IM stress several hours after the drug SA period [Unpaired-Stress (UP-S) groups], or to no IM stress [Control (C) groups]. The P-S and PP-S groups increased their drug SA during choice days in which both the opioid solution and water were available, and tended to manifest a more severe withdrawal syndrome after a naloxone challenge compared with the UP-S and C groups. Reinstatement of the opioid SA under conditions of paired-stress or no stress was further examined after 3 weeks without exposure to either stress or drugs. The paired stress animals had higher levels of drug SA and manifested a more severe withdrawal syndrome than those tested without stress. These results indicate that the learned association between exposure to stress and the drug availability may mediate, in part, the stress-induced enhancement of opioid SA and withdrawal effects. PMID- 7870991 TI - Investigation of the involvement of opioid receptors in the action of anticonvulsants. AB - This study investigates the possible involvement of opioid receptors in the action of a variety of anticonvulsant agents. The opioid antagonist naloxone (0.3, 1 mg/kg IP) and the selective mu-opioid antagonist cyprodime (3 mg/kg IP) significantly inhibited the increase in electroshock seizure threshold induced by phenytoin (3 mg/kg IP) in mice. The anticonvulsant effects of ethanol (1 g/kg IP) were also significantly antagonised by naloxone (1 mg/kg IP) but not by a 0.3 mg/kg IP dose or by cyprodime (3 mg/kg IP). The results with naloxone were confirmed using higher doses of phenytoin (10 mg/kg IP) and ethanol (1.5 g/kg IP). In contrast to the above findings, naloxone (0.3, 1 mg/kg IP) had no effect on the increase in seizure threshold induced by sodium valproate (200 mg/kg IP) or dizocilpine (MK801, 0.5 mg/kg IP) and paradoxically potentiated the increase in seizure threshold produced by phenobarbitone (15 mg/kg IP); carbamazepine (10 mg/kg IP) and the benzodiazepine agonist loprazolam (1 mg/kg IP), clearly differentiating these compounds from phenytoin and ethanol. These findings suggest that the anticonvulsant effects of phenytoin and ethanol (as assessed by their ability to prevent tonic hindlimb extension in the mouse electroshock model) may be mediated, at least in part, by the release of endogenous opioids and subsequent activation of opioid receptors (mu, in the case of phenytoin, but non-mu, in the case of ethanol) although direct activity at opioid receptors cannot be precluded. PMID- 7870992 TI - Trial 2 in the elevated plus-maze: a different form of fear? AB - A factor analysis of the scores from rats given two trials in the elevated plus maze showed that four independent factors emerged. Measures of anxiolytic activity on trial 1 (number of open arm entries and time spent on open arms) loaded on factor 1, measures of anxiolytic activity on trial 2 loaded on factor 2, the measure of general activity (number of closed arm entries) on both trials loaded on factor 3, and a measure of decision time (time spent in central square) for both trials loaded on factor 4. The independence of trials 1 and 2 anxiety measures raises the possibility that the state of anxiety/fear on the second trial in the plus-maze is qualitatively different from that on trial 1. This difference is reflected in the loss of anxiolytic action of diazepam (2 mg/kg) on trial 2. However, this occurs only when the trials are short (5 min); when they are longer (10 min) diazepam retains anxiolytic efficacy. It is concluded that during a brief (5 min) trial in the plus-maze rats acquire a specific phobic anxiety, which is relatively resistant to benzodiazepines. With a longer exposure to the plus-maze this form of fear extinguishes. PMID- 7870993 TI - Seizure threshold to lidocaine is decreased following repeated ECS (electroconvulsive shock). AB - Seizure susceptibility to lidocaine was investigated in rats which had received repeated ECS (electroconvulsive shock). In the first experiment three groups of rats received an ECS daily for 18 days, an ECS weekly for 18 weeks, and 18 sham treatments, respectively. Twelve weeks after the last ECS all rats received a lidocaine challenge (LC) in the form of an intraperitoneal (IP) injection of lidocaine (65 mg/kg). After the injection the animals were observed for occurrence of motor seizures. A total of 67% (10/15), 47% (7/15), and 0% (0/18) of the daily, weekly, and sham groups, respectively, had motor seizures in response to the LC. In the second experiment five groups of rats received an ECS daily for 0, 1, 6, 18, and 36 days, respectively. Eighteen weeks after the last ECS all rats received an LC and 0% (0/15), 13% (2/15), 20% (3/15), 53% (8/15), and 58% (7/12), respectively, developed seizures in response to the LC. In the third experiment two groups of rats received daily ECS and sham-ECS, respectively. Twenty-four hours after the last ECS all rats received an LC. A total of 60% (9/15) of the ECS group and 0% (0/10) of the sham-ECS group had seizures in response to the LC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870994 TI - Acute stress or corticosterone administration reduces responsiveness to nicotine: implications for a mechanism of conditioned tolerance. AB - We have shown that conditioned tolerance develops to some of the behavioral and endocrine effects of nicotine in rats. Other investigators have suggested that tolerance to multiple nicotine injections in mice may be due, in part, to elevated plasma corticosterone (CORT) levels, since repeated nicotine injections are associated with elevated CORT, chronically elevated CORT reduces nicotine responsiveness and adrenalectomy disrupts nicotine tolerance. Three experiments tested the feasibility of this hypothesis, as a mechanism for conditioned nicotine tolerance in rats, by determining whether acute administration of CORT or manipulations that increase adrenocortical activity reduce nicotine responsiveness. In experiment 1, male rats were injected IP with CORT (1 mg/kg), vehicle (ETOH + distilled water) or no injection 10 min before nicotine (0.75 mg/kg, SC) and tested for nicotine-induced analgesia every other day for 10 days. A significant reduction in withdrawal latencies was obtained for CORT pretreated rats compared to animals given only nicotine. A similar reduction was produced by the vehicle pretreatment, which itself induced an elevation of endogenous CORT. Experiments 2 and 3 established that similar effects could be produced by doses of CORT as low as 0.125 mg/kg or by exposure to a novel environment which also elevated CORT levels. Results also suggest that a conditioned release of endogenous CORT was triggered by stimuli associated with nicotine delivery. These data are consistent with the hypothesis that a conditioned release of CORT could contribute to the development of tolerance to some of nicotine's effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7870995 TI - Chronic treatments with cholinoceptor drugs influence spatial learning in rats. AB - Nicotine, scopolamine, oxotremorine, diisopropyl-fluorophosphate (DFP) and tetrahydroaminoacridine (THA) were administered chronically to different groups of rats in doses reported to alter central muscarinic and/or nicotinic receptor numbers. Beginning 24 h after final drug injection, the groups were compared to a vehicle control group on acquisition of a hidden platform position in the Morris water maze over 20 trials with a 30-min inter-trial interval. Chronic treatment with either nicotine or scopolamine significantly improved the rate of learning, but oxotremorine and DFP retarded learning and THA had no effect on learning. The chronic drug effects on behaviour were consistent with known effects of the injected drugs on muscarinic and nicotinic binding in the forebrain and on the sensitivity of frontal cortex neurones to iontophoretically applied cholinoceptor agonists. However, alternative explanations for the observed changes cannot be ruled out, since the drugs used are known to have a wide range of effects on other neurotransmitters. PMID- 7870997 TI - Ipsapirone and 8-OH-DPAT reduce ethanol preference in rats: involvement of presynaptic 5-HT1A receptors. AB - The selective serotonin(5-HT)1A receptor agonists 8-OH-DPAT and ipsapirone were tested in selectively inbred Wistar rats, with high preference [70-90%: defined as the ratio of ethanol (EtOH) to total fluid intake] for EtOH (10% v/v) over water in a two-bottle free choice situation. Rats were injected shortly before the overnight test session (8:00 P.M.-8:00 A.M.). EtOH and water consumption were determined in 20-min intervals; food consumption after the session. 8-OH-DPAT (ED50: 2.4 mg/kg, SC) and ipsapirone (ED50: 12.5 mg/kg, SC) reduced EtOH preference in a dose-dependent manner. In addition, 8-OH-DPAT increased total fluid intake, whereas ipsapirone enhanced total food intake. The EtOH preference reduction was time-dependent and reached a maximum within the second 4 h after application of 8-OH-DPAT (-73%) and ipsapirone (-72%). The preference reducing effect of ipsapirone (20 mg/kg, PO) was completely blocked by the nonselective 5 HT1A antagonist spiperone (0.05 mg/kg, SC). Local application of 8-OH-DPAT (10 micrograms, 0.5 microliters) into the dorsal raphe nucleus (DRN, a brain area rich in somatodendritic 5-HT1A autoreceptors), reduced the EtOH preference significantly as compared to the saline injection in the same animal (-12%, 8:00 12:00 P.M.). Only marginal effects on ingestion behavior were observed after microinjection into the nucleus accumbens. Reduction of brain 5-HT levels by pretreatment with the 5-HT synthesis inhibitor pCPA (2 x 150 mg/kg, IP) resulted in a short lasting, marked reduction (-54%) and a long lasting, small attenuation of the EtOH preference. Total food consumption was strongly decreased but returned soon to normal; total fluid intake was only slightly decreased. The EtOH preference reducing effect of ipsapirone (5 and 20 mg/kg, SC) was attenuated in pCPA-pretreated rats. The present data suggest that 5-HT1A receptor ligands reduce EtOH preference via stimulation of 5-HT1A receptors in the DRN. The possibility of additional mechanism(s) is discussed. PMID- 7870996 TI - 5-HT receptors as targets for the development of novel anxiolytic drugs: models, mechanisms and future directions. AB - The introduction of buspirone for the treatment of anxiety, together with the eventual suggestion of a mode of action involving the serotonin (5-HT)1A receptor subtype, has generated considerable research activity and renewed interest in the potential role of 5-HT in anxiety. The further identification of multiple 5-HT1 receptors, coupled with the possibility that these subtypes potentially are involved in discrete biobehavioral regulation and pathophysiological conditions, has greatly expanded the search for tools capable of probing these receptors and has raised hopes for a new generation of more specific compounds to treat other disorders associated with the 5-HT system such as depression, aggression, and sleep and eating disturbances. The involvement of 5-HT in anxiety has prompted a careful reevaluation of several traditional areas of research. This has included those methods used in the in vivo evaluation of drugs in preclinical animal test procedures used to assess potential anxiolytic activity, as well as the mechanisms associated with adaptive changes occurring during long-term drug administration. The proliferation of various procedures for studying the anxiolytic effects of 5-HT drugs has not always been accompanied by systematic behavioral and pharmacological validation. At the present time, this area of research is characterized by numerous inconsistent findings. Procedures that are objective and impartial to the behavioral effects of drugs provide distinct advantages for addressing some of these issues, as will the results from carefully controlled clinical studies. The main objective of this article is to provide an overview of the recent developments in research involving the 5-HT system and anxiety. The emphasis will be on the 5-HT1 receptor system and a review of the results in the predominant animal models used to evaluate these drugs, as well as an overview of the mechanisms currently believed to be responsible for the therapeutic activity of this class of compounds. Studies with the pigeon are reviewed, since this species appears distinctly sensitive to the anxiolytic-like effects of 5-HT1A drugs in conflict procedures. Although chronic administration of 5-HT1A drugs appears necessary for clinical anxiolytic and antidepressant activity, the most noteworthy neuropharmacological effects in animals seem to occur in 5-HT2 and, perhaps, 5-HT3 receptors which are downregulated. Studies summarizing the activity of drugs interacting with 5 HT1C/2 and 5-HT3 receptor sites are also discussed as they too may be involved in anxiety or the actions of anxiolytic drugs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7870998 TI - Effect of 5-HT3 receptor antagonists on the discriminative stimulus properties of morphine in rats. AB - 5-HT3 receptor antagonists, e.g. MDL72222, ondansetron and ICS205-930, have been previously reported to block a morphine (1.5 mg/kg)-induced conditioned place preference in rats. This finding suggests that these drugs may modify the morphine discriminative stimulus which underlies place conditioning. To study this further we have examined the effects of MDL72222, ondansetron and ICS205-930 against a morphine discriminative stimulus using a two-choice, food reinforced, operant paradigm. In an attempt to provide consistency with previous place conditioning studies, a morphine training dose of 1.5 mg/kg was used in addition to a higher 3 mg/kg dose which was studied in separate animals. Stimulus control of behaviour was attained at both morphine training doses, the characteristics of each being consistent with an effect at the mu opioid receptor. Ondansetron (0.001-1 mg/kg), MDL72222 (0.1-3 mg/kg), and ICS205-930 (0.001-1 mg/kg) all failed to consistently antagonise the morphine cue at both training doses, although a mild attenuation was seen in the 1.5 mg/kg group following pretreatment with an intermediate dose of ondansetron and ICS205-930 (both 0.01 mg/kg). The present results therefore suggest hat 5-HT3 antagonists do not block a morphine discriminative state, at least in rats. PMID- 7870999 TI - Antinociceptive effects of the kappa opioid, U50,488: lack of modulation by 5-HT2 antagonists. AB - The kappa opioid, U50,488, was examined alone and in combination with the 5HT2 antagonists, ketanserin, pirenperone and LY 53857. Squirrel monkeys responded under a shock titration procedure in which shock intensity increased every 15 s from 0.01 to 2.0 mA in 30 steps. Five responses terminated the shock for 15 s, after which the shock resumed at the next lower intensity. The level at which the monkeys kept the shock 50% of the time (median shock level/MSL) was determined. U50,488 alone produced dose-dependent increases in median shock level whereas none of the 5-HT2 antagonists altered responding under this procedure. When ketanserin (0.032-5.6 mg/kg) was administered in combination with U50,488, very high doses of ketanserin (3.2-5.6 mg/kg) shifted the U50,488 dose-effect curve to the left. Neither pirenperone (0.032-10.0 micrograms/kg) nor LY53857 (0.01-0.32 mg/kg) altered the U50,488 dose-effect curve in any monkey. Taken together, these data do not support a role for the 5-HT2 system in kappa-induced antinociception in the primate. PMID- 7871000 TI - Cross-familiarisation conditioned taste aversion procedure as a method to reveal stimulus resemblance between drugs: studies on the 5-HT1A agonist 8-OHDPAT. AB - In the present study a cross-familiarisation conditioned taste aversion (CTA) paradigm was utilized to reveal stimulus resemblance between the selective 5-HT1A agonist 8-OHDPAT and a variety of serotonergic and non-serotonergic drugs. In male mice, a 0.22 mg/kg dose of 8-OHDPAT was used as the reference compound inducing CTA. Dose-dependent effects of pre-exposure to 24 different test drugs on the magnitude of the 8-OHDPAT-induced CTA were tested as a measure for stimulus similarity between these test drugs and 8-OH-DPAT (the reference compound). Pre-exposure to 8-OH-DPAT itself, ipsapirone, buspirone, RU 24969, sertraline, d-amphetamine, LSD, metergoline and idazoxan effectively prevented the development of CTA induced by 8-OHDPAT. Pre-exposure to apomorphine, diazepam, SCH 23390, LiCl, spiperone, DOI, spiroxatrine, umespirone, pindolol, mCPP, haloperidol, MK 212, clonidine, quipazine and also 5-MeODMT was not effective in completely abolishing the CTA produced by 8-OHDPAT. It is concluded from these results that the relatively simple and fast cross-familiarisation taste aversion method is a suitable paradigm to study similarities in stimulus properties of different drugs. PMID- 7871001 TI - A randomized double-blind placebo-controlled study of tropisetron in the treatment of outpatients with generalized anxiety disorder. AB - The selective 5HT3 antagonist tropisetron was studied in 91 outpatients meeting DSM-III criteria for Generalized Anxiety Disorder. Following a placebo washout period of up to 1 week, one of three active treatments (tropisetron 0.5 mg, 5 mg, or 25 mg daily) or placebo was given for a further 3 weeks. After 7 days treatment termination rates due to inefficacy showed a statistically significant dose-related therapeutic effect of tropisetron. Similar effects were seen on the Hopkins Symptom Check List total score and the Global Impression Scale. The Hamilton Anxiety Scale showed a similar trend which, however, failed to reach statistical significance. At day 21 tropisetron showed significant dose-dependent effects on all anxiety-related outcome measures. The incidence of adverse events was low and the severity generally mild. Most frequent complaints were headache, nausea, constipation and nervousness. Laboratory tests and physical examination performed at baseline and study end showed no significant treatment effects. PMID- 7871002 TI - 5HT drugs in animal models of anxiety. AB - It has been widely accepted that 5HT neurones promote anxiety, in humans as well as in animal models. This could be termed the "classic" hypothesis and it has led to a determined search for drugs which reduce 5HT function, especially agents which have selective actions at 5HT receptor subtypes. However, these novel agents tend to have weak and/or variable effects in animal models and more detailed examination of their actions suggests that not all findings are accounted for by the classic hypothesis. There appear to be circumstances in which increased 5HT activity can reduce anxious behaviour. There is increasing evidence for multiple anxiety mechanisms, which may be able to explain differential patterns of drug effects within and between models. Animal models of anxiety may also detect non-anxiety factors: effects on cognition or on impulsivity could be reflected in some models. This could be important in the light of recent evidence that 5HT-selective reuptake inhibitors are effective in impulsivity disorders. The classic hypothesis of 5HT function in anxiety may be only one part of an increasingly complex story. Unravelling the rest of this story is likely to lead to new insights in our understanding of anxiety and related disorders. PMID- 7871003 TI - Similar ameliorating effects of benzomorphans and 5-HT2 antagonists on drug induced impairment of passive avoidance response in mice: comparison with acetylcholinesterase inhibitors. AB - Mice were trained to avoid electric shocks by means of step-down type passive avoidance learning tasks, and memory retention was measured 24 h after the training session. Memory impairment (amnesia) was produced by administering either p-chloroamphetamine (PCA), a serotonin (5-HT) releaser or scopolamine (SCOP), a muscarinic cholinoceptor antagonist, 30 min prior to the training session. Benzomorphans, 5-HT2 antagonists and acetylcholinesterase (AChE) inhibitors were administered immediately after the training session. PCA- but not SCOP-induced amnesia was attenuated by the post-training administration of two benzomorphans, (+)N-allylnormetazocine ((+)SKF-10,047) and (+/- )pentazocine ((+/ )PTZ). Similarly, PCA-induced amnesia was reversed by the post-training administration of 5-HT2 antagonists, ritanserin (RIT) and mianserin (MIA), but SCOP-induced amnesia was not. However, the AChE inhibitors, tetrahydroaminoacridine (THA) and physostigmine (PHY) attenuated both PCA- and SCOP-induced amnesia when administered immediately after the training session. These results indicated that benzomorphans and 5-HT2 antagonists have antiamnestic effects in mice, as do AChE inhibitors. In addition, it is interesting that the patterns of ameliorating effect of benzomorphans were similar to those of 5-HT2 antagonists, which differ from those of AChE inhibitors. PMID- 7871004 TI - Attenuation of some alcohol-induced mood changes and the desire to drink by 5-HT3 receptor blockade: a preliminary study in healthy male volunteers. AB - We studied the effect of the 5-HT3 receptor antagonist ondansetron (4 mg orally) on some of the psychological effects of a small dose of alcohol (580 ml of 3.6% alcohol content by volume of lager) in 16 healthy male volunteers using a double blind placebo controlled, Latin Square cross-over design. Pretreatment with ondansetron significantly attenuated several of the subjective pleasurable effects of alcohol, and also decreased the subjective desire to drink. These findings are consistent with preclinical studies suggesting that the reinforcing properties of alcohol may be attenuated by 5-HT3 receptor blockade. PMID- 7871005 TI - Ondansetron and alcohol pharmacokinetics. PMID- 7871006 TI - Increased 5-HT release mediates the anxiogenic response during benzodiazepine withdrawal: a review of supporting neurochemical and behavioural evidence. AB - This paper reviews the biochemical and behavioural evidence that the increased anxiety that occurs during benzodiazepine withdrawal is caused by increased 5-HT activity. In hippocampal slices taken from rats withdrawn for 24 h from chronic diazepam treatment (2 mg/kg/day for 21 days) there was a significant increase in K(+)-evoked release of [3H]5-HT and in 45Ca2+ uptake and both of these changes were reversed by the GABAB agonist, baclofen. Baclofen also reversed the anxiogenic response that is detected on withdrawal from chronic diazepam treatment. Other drugs that reduce 5-HT function (tianeptine which increases 5-HT uptake; buspirone, a 5-HT1A receptor agonist/partial agonist; zacopride, a 5-HT3 receptor antagonist) also reversed this anxiogenic response. Finally, we present data from a group of rats that did not develop tolerance to the anxiolytic effects of diazepam (2 mg/kg), even after 5 weeks treatment. This group failed to show an anxiogenic response on withdrawal from diazepam, nor was there an increase in hippocampal 5-HT release. We discuss the extent to which increased hippocampal 5-HT release can be causally linked to the increased anxiety during benzodiazepine withdrawal. PMID- 7871007 TI - Anticonflict effects of buspirone and chlordiazepoxide in pigeons under a concurrent schedule with punishment and a changeover response. AB - A procedure was developed with pigeons to extend the experimental analysis of punished behavior and the effects of anxiolytic drugs. Under this procedure the completion of a fixed-ratio requirement on a changeover key switched between two variable-interval schedules of reinforcement that were programmed on a second response key. Under one schedule, correlated with a green keylight, key pecks produced only food; under the second schedule, correlated with a red keylight, key pecks produced both food and electric shock. Pigeons were switched into the component with shock if they did not enter that component within 5 min. Parameter values of the variable-interval schedules were manipulated systematically and the effects of two clinically active anxiolytic drugs, buspirone and chlordiazepoxide, were examined. Responding was suppressed during the component with shock (punishment) and, under non-drug conditions, pigeons infrequently switched into the punishment component; changeover responses occurred rapidly when switched into the punishment component. Both buspirone (0.1-3.0 mg/kg) and chlordiazepoxide (3.0-30 mg/kg) increased punished responding at doses that had little effect on unpunished responding; d-amphetamine (0.3-5.6 mg/kg), which was studied only under one parameter of the variable-interval schedule, produced greater decreases in rates of punished responding than in unpunished responding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871008 TI - Effects of buspirone and ipsapirone on schedule induced polydipsia: comparison with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and raclopride. AB - In the present experiments, the effects of the azapirone anxiolytics, buspirone and ipsapirone, on excessive drinking induced by a FT-60 schedule of food delivery (schedule induced polydipsia, SIP) were investigated. Because buspirone is known to block dopamine receptors and both buspirone and ipsapirone act as agonists at the 5-HT1A receptor, their effects on polydipsia were compared to raclopride, an antagonist at D2 receptors, and 8-OH-DPAT, an agonist at the 5 HT1A receptor, thus providing information about the relative importance of the serotonergic and/or dopaminergic systems for the maintenance of polydipsia. The effects of all four drugs were investigated both acutely, and following repeated treatment. The doses employed were as follows: buspirone, 1.0, 3.0, and 10.0 mg/kg; raclopride, 0.05, 0.15, and 0.5 mg/kg; 8-OH-DPAT, 0.1, and 1.0 mg/kg and ipsapirone, 1.0, 3.0, 10.0 mg/kg. Administered acutely, the lowest doses of buspirone and raclopride did not alter drinking, whilst the low dose of 8-OH-DPAT significantly reduced polydipsia. These effects were reversed following repeated treatment over 16 successive days. Buspirone 1.0 mg/kg and 0.05 mg/kg raclopride reduced drinking, whilst tolerance developed to the effects of 0.1 mg/kg 8-OH DPAT. Ipsapirone, at low doses, was without effect on drinking. At high doses, all four drugs reduced drinking both acutely and chronically. Repeated treatment with buspirone (3.0, and 10.0 mg/kg) reduced licking and panel entries, but induced a selective decrease in licking at the low dose (1.0 mg/kg). Similar effects were seen following raclopride treatment, although the effects were less selective. 8-OH-DPAT and ipsapirone, in contrast reduced licking only at the highest dose, and both drugs increased panel entries as testing continued. The effects of buspirone resembled those of raclopride whereas the effects of ipsapirone resembled those of 8-OH-DPAT. Buspirone appears to act as a dopamine antagonist in this test. The effects of the drugs suggest that SIP depends upon motivational and performance factors which may be more sensitive to drug manipulation than potential underlying psychological factors such as anxiety or stress. PMID- 7871009 TI - Effects of repeated treatment with 5-HT1A agonists on active avoidance responding in the rat. AB - The behavioural effects of the serotonin 1A receptor (5-HT1A) agonist anxiolytics are generally examined after acute administration. The present study examined the effects of these substances during repeated treatment in the two-way active avoidance (Conditioned Avoidance Response, CAR) procedure. Previously it has been found that the prototypical 5-HT1A receptor agonist, 8-OH-DPAT, increases avoidance, apparently by increasing general activity, after repeated administration but not on acute administration. In the present study, it was demonstrated that this increase in activity can be blocked by the 5-HT1A receptor antagonists (-)alprenolol (also beta adrenergic antagonist) and (S)-UH-301, but not by the non-selective 5-HT antagonist metergoline. The relatively full 5-HT1A agonist, flesinoxan, and the partial 5-HT1A agonist, ipsapirone, had qualitatively similar effects to 8-OH-DPAT, although the effect of ipsapirone was clearly smaller in magnitude. Buspirone, the 5-HT1A partial agonist/dopamine D2 antagonist, markedly decreased activity, and thus avoidance of the shocks, in a manner similar to the antipsychotic drug, haloperidol. However, when the hypothermic effects of these compounds were investigated after acute administration, buspirone induced a strong hypothermic response in rats, like 8 OH-DPAT, whereas haloperidol had no effect. With the exception of buspirone, the effectiveness of these compounds in increasing activity in the CAR test appears to be related to their agonist efficacy at the 5-HT1A receptor. Similarities between the effects of these compounds and previously reported results with serotonin-depleting agents (Tenen 1967; Breese et al. 1974) suggest that the net effect of 5-HT1A agonists after repeated administration is to produce a functional reduction in 5-HT activity. The activity suppressing action of buspirone indicates that the dopamine antagonist activity of buspirone predominates in this procedure. PMID- 7871010 TI - An ethopharmacological analysis of the behavioral effects of 8-OH-DPAT. AB - Several behaviors associated with the serotonin syndrome have been reported in rats following administration of the 5-HT1A receptor agonist 8-OH-DPAT. The present investigation approached this phenomenon from an ethopharmacological perspective, and provided a detailed temporal analysis of the behavioral effects of this compound over a 2-h period, in both male and female rats in the home cage. In addition, in order to further characterize the nature of the forepaw treading and locomotor elements, and assess the extent of influence of the physical characteristics of the test arena, this study provided a detailed analysis of these behaviors in both the home cage and a large oval runway. In the initial analysis, the data indicate a distinct chronological sequence of effects following 8-OH-DPAT treatment. For example, "flat back" activity and lower lip retraction were apparent within a few minutes post-injection, the former dissipating after about 30 min and being replaced as the prepotent response by a more general (curved back) locomotor enhancement, while the latter effect remained throughout the 2-h test period. Interestingly, there were reliable gender differences in terms of the onset and disappearance of several behavioral components, with females generally being more rapidly affected, but recovering earlier than males. The detailed analysis of locomotor activity and forepaw treading would suggest that the locomotor syndrome primarily involves forward movement, heavily guided by the physical environment. Furthermore, forepaw treading would seem only to occur when an animal reaches a barrier and forward movement is briefly interrupted, as no reliable incidence of this behavior was observed in the open area of the test area. Together, these findings provide further characterization of the behavioral syndrome induced by 8-OH-DPAT, and indicate the importance of time post-administration, gender of the subject, and the physical characteristics of the test environment, when considering stereotypical drug effects. PMID- 7871011 TI - Diazepam and gepirone selectively attenuate either 20-32 or 32-64 kHz ultrasonic vocalizations during aggressive encounters. AB - Ultrasonic vocalizations (USV) in rats may communicate "affective" states, as they occur only in highly significant behavioral contexts such as during sex, aggression, exposure to painful or startling events. This proposal was evaluated in an experiment with adult male Long-Evans rats during agonistic encounters; specifically, the effects of diazepam, flumazenil and gepirone were studied on different types of USV emitted by intruder rats exposed to resident attacks and to "threat of attacks" (i.e., intruder protected within the home cage of the resident by a wire mesh cage). USV were readily emitted during agonistic encounters and consisted primarily of two distributions of pure tone whistles: 0.3- to 3-s, 20- to 32-kHz ("low") signals and 0.02- to 0.3-s, 32- to 64-kHz ("high") signals. A considerable repertoire of frequency modulated signals was observed and proved to be sensitive to the anxiolytic treatments. Diazepam (1-6 mg/kg) dose-dependently decreased high frequency USV during the threat of attack and decreased the mean pitch of the most predominant vocalizations but did not affect low frequency USV or the audible squeals (AS) in response to bites. Gepirone (0.3-6 mg/kg) dose-dependently decreased low frequency USV and did not affect high frequency USV or AS. Responses to thermal pain stimuli remained unaltered by all drugs, while walking duration was decreased and crouch postures were increased after diazepam but not after gepirone administration. Gepirone in the present dose range had minimal effects on submissive, exploratory and locomotor behaviors. The pattern of results is consistent with the proposal that low frequency USV reflect a heightened affective state which is ameliorated with 5HT1A but not benzodiazepine anxiolytics, and suggests that the suppression of high frequency USV in reaction to attacks or threats coincides with the sedative or muscle relaxant properties of these compounds. PMID- 7871012 TI - Chronic lithium treatment enhances the postsynaptic 5-HT1A receptor-mediated 5-HT behavioral syndrome induced by 8-OH-DPAT in rats via catecholaminergic systems. AB - The effects of antimanic agents, including lithium, carbamazepine, clonazepam and zotepine, on the postsynaptic 5-HT1A receptor-mediated behavioral and hypothermic responses induced by 8-OH-DPAT in rats, and on [3H]8-OH-DPAT binding to 5-HT1A receptors in the rat hippocampus were examined. Treatment with lithium (3 mEq/kg, IP) for 14 days enhanced forepaw treading, one component of the 5-HT behavioral syndrome induced by 8-OH-DPAT, and this enhancement by lithium was abolished by catecholamine depletion with reserpine or alpha-methyl-p-tyrosine, but not by 5 HT depletion with p-chlorophenylalanine. These data suggest that lithium enhances 5-HT1A-mediated behavior via catecholaminergic systems. In contrast, chronic lithium treatment did not alter the hypothermic response to 8-OH-DPAT in untreated rats, as well as in rats treated with reserpine. These findings strengthen the suggestion that lithium has no direct influence on the postsynaptic 5-HT1A-mediated response. Other antimanic agents had no effect on either forepaw treading or hypothermia induced by 8-OH-DPAT. Radioligand binding studies using [3H]-8-OH-DPAT demonstrated that chronic lithium treatment, but not other antimanic agents, caused 5-HT1A receptor down-regulation in rat hippocampus. A discrepancy therefore exists between 5-HT1A receptor down regulation and unaltered 5-HT1A-mediated behavioral and hypothermic responses in catecholamine-depleted rats after chronic lithium treatment. PMID- 7871013 TI - Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on timing behaviour investigated with an interval bisection task. AB - Seventeen rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei: 12 rats received sham injections. The rats were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus and to press lever B following an 8-s presentation of the same stimulus. Both groups learnt the task rapidly and maintained > 90% accuracy throughout the experiment. When stable performance had been attained, "probe" trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. The bisection point (duration corresponding to 50% choice of lever B) was significantly shorter in the lesioned group than in the control group. There was no significant difference between the slopes of the psychophysical functions or the Weber fractions derived for the two groups. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results confirm the involvement of 5HTergic function in timing behaviour, but suggest that destruction of these pathways does not disrupt the capacity for temporal discrimination. PMID- 7871014 TI - Does the effect of central 5-hydroxytryptamine depletion on timing depend on motivational change? AB - In a previous experiment we found that destruction of the ascending 5 hydroxytryptaminergic (5HTergic) pathways by microinjection of 5,7 dihydroxytryptamine into the dorsal and median raphe nuclei resulted in impaired acquisition of temporal differentiation under an interresponse-time-greater-than 15-s (IRT > 15 s) schedule of sucrose reinforcement. This paper reports three experiments, the results of which bear on the interpretation of that finding. In Experiment 1, 32 rats were trained for 120 sessions under the IRT > 15 s schedule; then 16 received lesions of the 5HTergic pathways and 16 received sham lesions. Comparisons of the IRT frequency distributions of the two groups showed that the lesion produced a significant reduction of the mean IRT and an increase in the dispersion of IRTs, as expressed by the coefficient of variation. Obtained reinforcement rates were significantly reduced in the lesioned group, but response rates were not significantly altered. Levels of 5HT and 5 hydroxyindoleacetic acid were markedly reduced in all forebrain areas examined, without significant change in noradrenaline and dopamine levels. The results indicate that destruction of the 5HTergic pathways disrupts performance as well as acquisition of temporal differentiation. Experiments 2 and 3 examined whether changes in deprivation level and reinforcer magnitude, which are known to affect reinforcer value, would influence temporal differentiation in a similar fashion to destruction of the 5HTergic pathways. In experiment 2, 20 rats were trained under the IRT > 15 s schedule while maintained at 80% or 90% of free-feeding body weight; the more severe deprivation condition was associated with a longer mean IRT and a lower coefficient of variation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871015 TI - Modification of behavioral effects of cocaine by selective serotonin and dopamine uptake inhibitors in squirrel monkeys. AB - Modification of the behavioral effects of cocaine by the selective serotonin (5 HT) uptake inhibitors citalopram and fluoxetine and the selective dopamine (DA) uptake inhibitor GBR 12909 was investigated in squirrel monkeys trained under a fixed-interval schedule of reinforcement or a two-lever cocaine-discrimination procedure. Under the fixed-interval schedule cocaine (0.03-1.78 mg/kg) produced dose-related increases in response rate, reaching an average maximum of 215% of control after a dose of 0.3 mg/kg. Similar rate-increasing effects were seen with GBR 12909 (3.0 or 10.0 mg/kg), but not citalopram (10.0 or 17.8 mg/kg) or fluoxetine (10.0 mg/kg). Pretreatment with citalopram or fluoxetine attenuated the rate-increasing effects of cocaine and produced an overall downward shift in the cocaine dose-response function. Pretreatment with GBR 12909, on the other hand, produced an overall leftward shift in the cocaine dose-response function. Under the drug-discrimination procedure cocaine (0.03-1.78 mg/kg) engendered dose related increases in the percentage of cocaine-appropriate responses, as did GBR 12909 (1.0-17.8 mg/kg) but not citalopram (1.0-17.8 mg/kg). Pretreatment with citalopram attenuated the discriminative stimulus effects of cocaine and produced an overall rightward shift in the cocaine dose-response function, whereas pretreatment with GBR 12909 produced an overall leftward shift in the cocaine dose-response function. The results show that selective 5-HT and DA uptake inhibitors can modify the rate-altering and discriminative stimulus effects of cocaine in qualitatively different ways and suggest a modulatory role for 5-HT uptake inhibition in the behavioral effects of cocaine. PMID- 7871017 TI - Differences in morphine reinforcement property in two inbred rat strains: associations with cortical receptors, behavioral activity, analgesia and the cataleptic effects of morphine. AB - The purpose of the current study was to investigate genetic differences between two inbred strains of rats, Fisher-344 (F344/N) and Wistar Albino Glaxo (WAG/GSto), in a number of drug-naive and drug-related behaviors, including oral and intravenous morphine self-administration. F344/N and WAG/GSto rats differed in drug-naive behaviors such as nociception, rearing and sensitivity to lick suppression tests but did not differ in locomotor activity, ambulation or grooming behavior. F344/N rats were less sensitive to thermal stimuli as measured via tail-flick response, and more sensitive to the suppressive effects of intermittent shock in a lick suppression test. The F344/N rats demonstrated a significantly greater amount of rearing in open field tests but did not differ from WAG/GSto rats in locomotor activity, ambulation or grooming behavior. In addition to the behavioral results, naive F344/N and WAG/GSto rats were found to differ in mu and alpha 2 receptor concentrations (F344/N > WAG/GSto) and in 5HT2 and D2 affinity constants (WAG/GSto > F344/N). These two inbred rat strains also differed in drug-related behaviors. F344/N rats showed significantly greater depression of locomotor activity at morphine 3 mg/kg than WAG/GSto rats. In addition, F344/N rats consumed significantly greater amounts of morphine in a two bottle choice procedure and morphine maintained significantly greater amounts of behavior during intravenous self-administration sessions. Importantly, drug maintained behavior was significantly greater than with vehicle only in the F344/N rats during operant self-administration sessions. PMID- 7871018 TI - Rewarding and aversive properties of IP and SC cocaine: assessment by place and taste conditioning. AB - Three experiments were conducted to compare the effectiveness of intraperitoneally (IP) administered or subcutaneously (SC) administered cocaine to produce place and/or taste conditioning after four conditioning trials. In each experiment, IP (5-20 mg/kg) cocaine produced a place preference, but SC (0.5 20 mg/kg) cocaine at concentrations that prevented necrosis, did not produce a place preference. The failure of SC cocaine to produce a place preference was not a function of conditioning trial duration. On the other hand, SC cocaine (20 mg/kg) produced conditioned taste avoidance, but IP cocaine (20 mg/kg) did not produce conditioned taste avoidance. The results suggest that IP cocaine, but not SC cocaine, is rewarding. PMID- 7871016 TI - Animal models of drug craving. AB - Drug craving, the desire to experience the effect(s) of a previously experienced psychoactive substance, has been hypothesized to contribute significantly to continued drug use and relapse after a period of abstinence in humans. In more theoretical terms, drug craving can be conceptualized within the framework of incentive motivational theories of behavior and be defined as the incentive motivation to self-administer a psychoactive substance. The incentive motivational value of drugs is hypothesized to be determined by a continuous interaction between the hedonic rewarding properties of drugs (incentive) and the motivational state of the organism (organismic state). In drug-dependent individuals, the incentive-motivational value of drugs (i.e., drug craving) is greater compared to non-drug-dependent individuals due to the motivational state (i.e., withdrawal) developed with repeated drug administration. In this conceptual framework, animal models of drug craving would reflect two aspects of the incentive motivation to self-administer a psychoactive substance. One aspect would be the unconditioned incentive (reinforcing) value of the drug itself. The other aspect would be relatively independent of the direct (unconditioned) incentive value of the drug itself and could be reflected in the ability of previously neutral stimuli to acquire conditioned incentive properties that could elicit drug-seeking and drug-taking behavior. Animal models of drug craving that permit the investigation of the behavioral and neurobiological components of these two aspects of drug craving are reviewed and evaluated. The models reviewed are the progressive ratio, choice, extinction, conditioned reinforcement and second-order schedule paradigms. These animal models are evaluated according to two criteria that are established herein as necessary and sufficient criteria for the evaluation of animal models of human psychopathology: reliability and predictive validity. The development of animal models of drug craving will have heuristic value and allow a systematic investigation of the neurobiological mechanisms of craving. PMID- 7871020 TI - Proconvulsive effects of histamine H1-antagonists on electrically-induced seizure in developing mice. AB - The purpose of this study was to investigate the developmental differences in seizure susceptibility in mice and the roles of the histaminergic neuron system in inhibition of convulsions in development. First, we studied developmental differences in electrically-induced seizures. Since the 14-day-old mice showed a different seizure pattern from that of older mice, we evaluated the seizure susceptibility of mice older than 21 days. The durations of all the convulsive phases were significantly increased in 21- and 30-day-old mice, compared with older mice. Second, pyrilamine (or mepyramine), ketotifen, and d chlorpheniramine, centrally-acting H1-antagonists, increased the durations of all the convulsive phases in the 21- and 30-day-old mice, but did not increase duration in 42-day-old mice. Terfenadine and astemizole, H1-antagonists that hardly enter the brain, did not affect the durations of all the convulsive phases in 21-, 30- and 42-day-old mice. The proconvulsant effect of centrally-acting H1 antagonists in 21- and 30-day-old mice were considered to be mediated via the central H1-receptors. Thus, the histaminergic neuron system may have an important physiological role in inhibition of seizures in 21- and 30-day-old mice which have higher seizure susceptibility. This would compensate for the immaturity of the other protective neuron systems such as NMDA receptor complexes and GABA receptors. In conclusion, the present findings support the view that the central histaminergic system plays a role in inhibition of convulsions. PMID- 7871019 TI - Selective serotonin re-uptake inhibitors decrease schedule-induced polydipsia in rats: a potential model for obsessive compulsive disorder. AB - Schedule-induced polydipsia was used to determine the effects of selective serotonin re-uptake inhibitors on adjunctive water consumption. Polydipsia was induced in food deprived rats by exposure to a fixed time feeding schedule (FT = 60 s) for 150 min per day for 22 days. Selected polydipsic rats consumed 3-4 times greater volume of water compared to food deprived control rats. Chronic administration of the selective serotonin re-uptake inhibitors fluoxetine and clomipramine (CMI) at 5 mg/kg per day and fluvoxamine at 10 mg/kg twice a day significantly decreased schedule-induced polydipsia (SIP) on day 15 and throughout the remainder of the study compared to control rats. The noradrenergic re-uptake inhibitor, desipramine (DMI), only decreased SIP behavior on day 1. The neuroleptic, haloperidol (0.03 and 0.1 mg/kg), and the benzodiazepine, diazepam (2.5 mg/kg), failed to alter SIP behavior. Since obsessive-compulsive disorder (OCD) and polydipsic behavior both involve excessive expression of a normal behavior, the polydipsia model may be relevant for the prediction of compounds useful in the treatment of OCD. PMID- 7871021 TI - Concurrent pentobarbital- and saccharin-maintained responding: effects of saccharin concentration and schedule conditions. AB - Responses of rhesus monkeys were reinforced by delivery of either a pentobarbital (4.0 mg/ml) solution or a vehicle (water) or saccharin solution under a concurrent signaled differential reinforcement of low rates 30-s schedule. After 30 s of no responding, the first response on the pentobarbital or saccharin spout resulted in the delivery of the appropriate solution and reset the timing on both spouts (i.e. a mutually exclusive choice). In the first experiment, the concentration of saccharin was gradually increased across sessions. As saccharin concentration increased, pentobarbital deliveries decreased and saccharin as well as total session deliveries increased. In a second experiment, pentobarbital and 0.24 (mg/ml) saccharin were made available under concurrent signaled differential reinforcement of low rates 30-s schedules which operated independently. Under these conditions responding on one spout had no consequences with respect to the other spout. The reduction of pentobarbital deliveries was substantially attenuated when the choice was not mutually exclusive. PMID- 7871022 TI - Individual differences in the feeding effects of amphetamine: role of nucleus accumbens dopamine and circadian factors. AB - Evidence indicates that amphetamine (AMP) affects feeding in a baseline-dependent fashion and that the nucleus accumbens (Acc) is an important site of action for AMP's effects on feeding. Experiment 1 examined the contribution of Acc-dopamine (DA) mechanisms to the baseline-dependent feeding effects of a 0.125 mg/kg dose of AMP using intra-Acc administrations of cis-flupenthixol (FLU). Results showed that there was an inverse relation to AMP, such that AMP stimulated feeding in animals with high baseline intake. Intra-Ace FLU administration reversed the stimulatory but not the inhibitory effect of AMP. Further, intra-Acc FLU attenuated baseline feeding in high but not low baseline feeders. Experiment 2 sought to determine whether AMP would affect feeding in a baseline-dependent manner when administered in the dark photoperiod of the rat circadian cycle, when rats do most of their feeding. To this end, rats were administered three doses (0.05,0.01, and 0.25 mg/kg) of AMP in the dark photoperiod and the intake of sugar monitored. Results showed that in low baseline feeders, AMP stimulated intake at lowest dose and had no effect at higher doses. In high baseline feeders, AMP inhibited intake in a dose-dependent manner. Taken together, these results further establish that AMP affects feeding in a baseline-dependent fashion. Moreover, the similar effects of AMP across the light and dark photoperiods suggest that a straightforward rate-dependency interpretation is not adequate. Finally, it is speculated that Acc-DAergic activity may play a role in the observed differences in baseline intake levels and in the response to AMP. PMID- 7871023 TI - SR 46559A: a novel and potent muscarinic compound with no cholinergic syndrome. AB - The cholinergic activities of SR 46559A, 3-[N-(2 diethyl-amino-2-methylpropyl)-6 phenyl-5-propyl] pyridazinamine sesquifumarate, have been investigated in vitro and in vivo, in rodents. Using rat brain cortical membranes, SR 46559A was a competitive ligand (Ki = 112 nM) at muscarinic M1 receptors, its affinity for muscarinic M2 (cardiac) and M3 (glandular) receptors being 6-7 times lower. SR 46559A did not interact with brain nicotinic receptors and high affinity choline uptake sites nor did it inhibit brain acetylcholinesterase activity. In contrast to reference muscarinic agonists, SR 46559A (1 mM) did not inhibit the forskolin induced activation of cAMP synthesis nor did it stimulate phosphoinositides breakdown in various brain preparations. However, this compound enhanced (+67% at 1 mM) diacylglycerol formation in rat striatal miniprisms, an effect fully reversed by atropine. As shown with reference agonists, SR 46559A inhibited (IC50 = 10 microM) the K(+)-evoked release of [3H]GABA from rat striatal slices and reduced at 0.5 and 1 microM, the population spike amplitude of the CA1 pyramidal cells induced by stimulation of the Schaffer's collateral commissural pathway in rat hippocampal slices. In mice, SR 46559A at a near lethal dose (200 mg/kg PO) did not induce the typical cholinergic syndrome nor did it modify at 30 mg/kg PO the oxotremorine-induced hypothermia. Like muscarinic agonists, SR 46559A (1 mg/kg PO) potentiated haloperidol-induced catalepsy in rats and inhibited (ED50 = 0.12 mg/kg PO) rotations induced in mice by intrastriatal injection of pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871024 TI - Tyrosine ameliorates a cold-induced delayed matching-to-sample performance decrement in rats. AB - Exposure to cold stress has been shown to impair short-term, or working, memory which may be related to a reduction in brain catecholamines. Administration of the catecholamine precursor tyrosine may alleviate a cold-stress-induced memory impairment by preventing a deficit in brain catecholamine levels. To test this hypothesis, eight rats performed a delayed matching-to-sample (DMTS) task at an ambient temperature of either 2 degrees C (cold) or 22 degrees C, following intraperitoneal administration of saline or tyrosine (50, 100 or 200 mg/kg). Rats administered saline prior to 22 degrees C exposure demonstrated a characteristic delay gradient in which accuracy decreased as the delay interval between sample and comparison stimuli increased from 1 to 16 s. Consistent with previous research, and relative to 22 degrees C exposure sessions, matching accuracy during 2 degrees C exposure sessions was reduced, which is attributed to the effect of cold on short-term, or working, memory. In particular, during cold exposure sessions matching accuracy was significantly reduced at the longer delay intervals, relative to matching accuracy at 22 degrees C. Additional analysis of cumulative matching errors within sessions showed that during exposure to cold, errors occurred at a constant rate throughout the session, indicating rats' performance was equally debilitated by the stressor over the entire session. During cold exposure sessions, the higher doses of 100 and 200 mg/kg tyrosine significantly improved overall matching accuracy relative to saline, but did not completely reverse the effect of cold exposure, as overall matching accuracy did not increase entirely to levels obtained at 22 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871025 TI - Anatomical differentiation within the nucleus accumbens of the locomotor stimulatory actions of selective dopamine agonists and d-amphetamine. AB - The effects of local injections of dopamine receptor agonists into various areas within the nucleus accumbens or the medial caudate-putamen on the generation of locomotor activity were examined. Combinations of 0.32 microgram/side of the dopamine receptor agonists SKF 38393 (D1) and quinpirole (D2) produced increases in locomotor activity that varied according to the rostral-caudal placement of the cannulae within the nucleus accumbens. The greatest levels of locomotion were generated by injections into a region in the caudal-central nucleus accumbens, with lower levels of activity elicited by injections into more rostral or caudal regions. A similar pattern of responses was produced by administration of the indirect dopamine agonist d-amphetamine. These results indicate that there is marked heterogeneity in the response of discrete sub-regions of the nucleus accumbens to dopamine receptor stimulation and that this heterogeneity is functionally expressed in the mediation of the locomotor effects of dopaminergic agonists. PMID- 7871026 TI - A comparison of behaviour following stimulation of the anterior substantia nigra by direct cholinergic agonists and anticholinesterases. AB - Microinjections of carbachol, a muscarinic cholinergic receptor agonist, into the anterior substantia nigra increase feeding, drinking and sexual behaviour if there is a pre-existing tendency to respond and a low baseline rate of behaviour. The present experiment was undertaken to compare the effects of carbachol with other cholinergic stimulants. Groups of 6-12 satiated rats received 0.5 microliter microinjections into the anterior substantia nigra of 0.1-5.0 micrograms carbachol, 0.1-5.0 micrograms nicotine, 2.5-10.0 micrograms eserine, and 1.25-5.0 micrograms or 0.1-1.0 microgram neostigmine (each dissolved in sterile saline) and the effects on feeding, drinking, locomotion, grooming, rearing and sniffing were examined. Carbachol, nicotine and low doses of neostigmine stimulated eating in a dose-dependent manner. The increased feeding following neostigmine was over a shorter time-period than following carbachol or nicotine. Neither carbachol nor nicotine had any significant effect on behaviour other than eating. The higher doses of neostigmine increased the frequency of sniffing and rearing, but not eating, and no dose of eserine had a clear effect on behaviour. These data are discussed in terms of their relationship to the cholinergic input to substantia nigra which excites pars compacta dopamine containing neurones. PMID- 7871027 TI - Effects of oxotremorine on inhibitory avoidance behaviour in two inbred strains of mice: interaction with 5-methoxy-NN-dimethyltriptamine. AB - The effects of the cholinergic muscarinic agonist, oxotremorine (0.005, 0.01, 0.02 and 0.04 mg/kg), the serotonergic agonist, 5-methoxy-NN-dimethyltriptamine (5-MeODMT) (0.5, 1 and 2 mg/kg), and their combination, were investigated in C57BL/6 and DBA/2 mice using a one-trial inhibitory avoidance task, drug treatment being given immediately after the acquisition trial. Post-trial administration of oxotremorine facilitated, while post-trial administration of 5 MeODMT inhibited memory retention of both strains in a dose-dependent fashion. The DBA/2 strain was more affected by oxotremorine than the C57BL/6 mice; no strain-dependent sensitivity to serotonergic agonist administration was observed. In both strains, the combination of oxotremorine plus 5-MeODMT inhibited the performance improvement shown by the administration of the cholinergic agonist alone. The facilitatory role of cholinergic stimulation on retention performance was confirmed and an inhibitory action of the serotonergic system on memory processes was suggested. Moreover, the present results support a functional interaction between cholinergic and serotonergic systems on memory consolidation. PMID- 7871028 TI - Nicotine or tar titration in cigarette smoking behavior? AB - A significant problem in assessing the relative relevance of nicotine and tar yield for compensatory smoking after switching from high to low yield cigarettes is that nicotine and tar yield are highly intercorrelated across conventional cigarettes and that the tar/nicotine ratios vary only within a modest range. A better differentiation between the impacts of nicotine and tar yield was expected by comparing in a laboratory experiment a new low nicotine/medium tar cigarette ("Next") with conventional low nicotine/low tar (ultra-light) cigarettes and with medium nicotine/medium tar cigarettes with respect to nicotine absorption and physiological effects. Twelve females, habitually smoking medium type cigarettes (> or = 0.7 mg nicotine) participated in the study. Neither the number of cigarettes smoked under field conditions nor the puffing behavior during the laboratory experiment differed between the three types of cigarettes. In the laboratory, Next produced only very small increases in plasma nicotine and changes in cardiovascular or EEG measures, whereas the effects of the medium cigarettes were in the expected range and those of the ultra-light cigarettes about halfway in between. The nicotine absorption/nicotine yield and the CO absorption/CO yield ratios were similar for Next and the habitual cigarettes, but about twofold higher for the ultra-light cigarettes. This suggests that gustatory and olfactory sensations, which are supposed to be more dependent on tar than on nicotine yield, may play a greater role for the regulation of smoking behavior than hitherto believed. PMID- 7871029 TI - Ethanol regulated preference in rats. AB - A series of experiments evaluated the determinants of preference for mixtures of ethanol plus sucrose relative to sucrose in rats. One dipper served 10% ethanol mixed with 10% sucrose, and the second dipper served 10% sucrose. Lever presses operated each dipper according to a variable-interval 5-s schedule. In three experiments the subjects were given pre-session meals of sucrose (2.5-20 ml) or sucrose (20 ml) plus chow (5 or 10 g). Pre-session meals decreased responding maintained by sucrose but not responding maintained by ethanol mixture. In two experiments body weight was varied from 85% to 125% of the initial free-feeding values. Increases in body weight, like pre-session meals, decreased responding reinforced by sucrose, but typically did not decrease responding reinforced by ethanol mixture. Throughout most of the study, ethanol consumption remained at about 1.25 ml per half hour session (3-4 g/kg per 30 min). For example, pre session access to ethanol mixture decreased within-session ethanol consumption, but total consumption, counting both sources, remained about 1.25 ml/session. The within-session patterns of responding also differed. Responding reinforced by ethanol mix decreased as a function of ethanol consumption, whereas responding reinforced by sucrose was relatively constant throughout the session. The simplest explanation of the results is that ethanol's pharmacological consequences regulated preference. PMID- 7871030 TI - Centrally acting drugs act as conditioned stimuli in a conditioned suppression of drinking task. AB - An experiment was conducted to test whether centrally acting drugs could act as conditioned stimuli (CS) in a classical conditioning paradigm in which electric shock acted as the unconditioned stimulus (US) and suppression of drinking was used as an indicator of a conditioned response (CR). Thirsty rats were allowed to drink water during daily classical conditioning sessions which took place in their home cages. The CS was either a drug injected before the session or a "cocktail" of sensory stimuli (light + tone + vibration) turned on at the beginning of the session. Part way through some sessions the animals received electric foot shock as the US. Two different drugs and the sensory cocktail were used as CSs in a discriminated classical conditioning paradigm in which one drug or stimulus (the CS+) predicted the subsequent occurrence of shock, and the other two conditions acted as CS- stimuli and predicted absence of shock. After an average of 5.7 pairings of the CS+ with shock, conditioned suppression of drinking was observed; the CR occurred only during tests preceded by the CS+ drug or stimulus. At one time or another during the experiment, pentobarbital, phencyclidine, morphine, and pentylenetetrazol were employed as the CS+. Each acquired the ability to elicit a CR, although pentobarbital was noticeably less effective than the other three drugs. All conditioning trials took place in hanging metal cages, but the CR generalized into plastic cages with sawdust floors. Each rat received three successive phases of conditioning with a different CS+ condition employed in each phase; each phase of conditioning was followed by extinction of the CR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871031 TI - Morphine as a conditioned stimulus in a conditioned emotional response paradigm. AB - A Pavlovian conditioning experiment was conducted to determine whether morphine (6 mg/kg, IP) could act as a conditioned stimulus (CS) when paired with an electric shock unconditioned stimulus (US), and later produce a conditioned suppression of drinking (CR) in water deprived rats. Seven groups were tested for conditioning after exposure to one of the following conditioning procedures: (1) morphine paired with shock; (2) morphine alone with no shock; (3) shock but no morphine; (4) no shock and no morphine; (5) morphine paired with vocalizations of shocked rats; (6) saline paired with shock; (7) saline alone with no shock. Groups 1 and 2 tested whether morphine could act as a CS. Groups 3 and 4 tested for sensitization. Group 5 tested whether exposure to the vocalizations of other rats could act as a US when paired with a morphine CS. Groups 6 and 7 tested whether cues associated with the injection procedure could act as a CS. Only subjects in group 1 showed conditioned suppression of drinking, when compared to control groups. Overall, the results indicate that morphine could act as a conditioned stimulus and that several of the more obvious possible sources of artifact did not significantly contribute to the CR that is produced. PMID- 7871032 TI - Seroquel: biochemical profile of a potential atypical antipsychotic. AB - Seroquel and the atypical antipsychotic clozapine were compared using a number of biochemical measures in rats which are indicative of potential antipsychotic activity and possible extrapyramidal side effect liability. Both in vitro and in vivo, these compounds are low potency D-2 dopamine (DA) receptor antagonists and are relatively more potent 5-HT2 antagonists than typical antipsychotic drugs. Seroquel also exhibited low affinity for D-1 DA receptors in vitro, but D-1 receptor occupancy was not detectable in vivo. Unlike clozapine, Seroquel lacks appreciable activity at either D-1 DA or muscarinic receptors. Following IP administration, both compounds produce similar elevations in DA metabolite concentrations. Following 1 month of daily administration, at doses which produce large increases in striatal DA metabolite concentrations, both Seroquel and clozapine fail, unlike typical antipsychotics, to increase the number of striatal D-2 receptors, but do decrease the number of 5-HT2 receptors in frontal cortex. ICI 204,636 produces a short-lasting increase in plasma prolactin levels, but these increases are much greater than those that are produced by clozapine. One day after 3 weeks of daily administration, tolerance, to the ability of Seroquel to elevate DA metabolite and plasma PRL concentrations is not observed. These biochemical observations are discussed with regard to the atypical profile of Seroquel in behavioral and electrophysiological studies. PMID- 7871033 TI - Seroquel: electrophysiological profile of a potential atypical antipsychotic. AB - Extracellular single unit recording techniques were employed to compare the effects of seroquel with the reference antipsychotic (AP) agents clozapine and haloperidol in electrophysiological tests that may predict AP activity. Seroquel and clozapine were differentially more active in reversing the inhibitory actions of d-amphetamine on mesolimbic (A10) than nigrostriatal (A9) dopamine (DA) containing neurons, whereas haloperidol exhibited the opposite selectivity. In cell population studies, acute treatment with seroquel and clozapine selectively increased the number of spontaneously active A10 DA cells, which was found to correlate with the ability of both these drugs to cause depolarization inactivation (DI) of A10 DA cells following repeated (28 day) administration. This profile of activity was unlike that of haloperidol, which acutely caused a nonselective increase in the number of active A9 and A10 DA cells, associated with the ability of this agent to cause DI of both A9 and A10 DA cells after repeated treatment. Since DI of A10 DA cells may be correlated with AP efficacy whereas DI of A9 DA cells may predict the ability of an AP to cause extrapyramidal side effects (EPS) and tardive dyskinesia (TD), seroquel, like clozapine, may be an atypical AP with a reduced likelihood for producing EPS/TD. PMID- 7871034 TI - Seroquel: behavioral effects in conventional and novel tests for atypical antipsychotic drug. AB - Seroquel was compared to clozapine and several other antipsychotic agents in tests predictive of antipsychotic activity or extrapyramidal symptoms. In the conditioned avoidance test in squirrel monkeys as well as several paradigms using apomorphine or amphetamine-induced behavioral alterations, seroquel displayed the profile of a drug with potential antipsychotic activity. In these paradigms the potency of seroquel was somewhat less than clozapine in rodent tests, while the reverse was true in higher species, i.e. monkeys, cats. In tests designed to evaluate the propensity to induce EPS or tardive dyskinesia, for example, the production of dyskinetic reactions in haloperidol-sensitized cebus monkeys, seroquel displayed a profile similar to clozapine and disparate from typical antipsychotic drugs. In drug-naive cebus monkeys seroquel sensitized significantly fewer monkeys than haloperidol and the dyskinetic reactions were of significantly less intensity. It is anticipated that this novel antipsychotic agent will have a significantly reduced propensity to produce extrapyramidal symptoms and tardive dyskinesia than typical antipsychotics. PMID- 7871035 TI - Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and 11C raclopride. AB - Positron emission tomography (PET) and 11C-raclopride were used to measure the occupancy of central dopamine D2 receptors by a new neuroleptic, CP-88,059-1. In a double blind dose escalation study, seven healthy male subjects received a predose of between 2 mg and 60 mg CP-88,059-1, 5 h before PET scanning. One additional subject was assigned to placebo predose. Receptor occupancy was defined as the percentage reduction in binding potential compared with that seen in the subject predosed with placebo and with that seen in seven unmedicated normal volunteers previously studied. Binding of 11C-raclopride decreased in a dose dependent manner, and 85% dopamine D2 receptor occupancy was achieved with the highest dose of CP-88,059-1. The findings confirm that brain dopamine D2 receptors are blocked by CP-88,059-1 and suggest that an effective antipsychotic dose will be between 20 mg and 40 mg. The study high-lights the potential of positron emission tomography in the preclinical evaluation of new drugs. PMID- 7871036 TI - Effects of antipsychotic drugs on latent inhibition: sensitivity and specificity of an animal behavioral model of clinical drug action. AB - Latent inhibition (LI) of a conditioned emotional response (CER) has been proposed as a quantitative measure of selective attention. We have assessed the parallels of the pharmacology of LI in rats with the clinical pharmacology of schizophrenia. Drug and vehicle treated rats were divided into groups and preexposed 20 times to cage illumination as a CS, or not preexposed. All groups were conditioned with 2 CS-footshock pairings. The following day CER, as measured by interruption of drinking in response to CS presentation, was recorded. LI was observed as a decreased CER in preexposed relative to non-preexposed animals. LI was enhanced by haloperidol 0.3 mg/kg after 7 or 14 daily treatments, but not after a single acute dose. Haloperidol doses of 0.3 and 0.03 mg/kg enhanced LI, while doses of 0.003 and 3.0 mg/kg had no effect. Haloperidol enhancement of LI was unaffected by the coadministration of the anticholinergic agent trihexyphenidyl. Enhancement of LI is exhibited by the antipsychotic drugs fluphenazine, chlorpromazine, thiothixene, thioridazine, mesoridazine, and metoclopramide but not clozapine. The non-antipsychotic drugs pentobarbital, imipramine, chlordiazepoxide, trihexyphenidyl, and promethazine failed to enhance LI. LI exhibits striking parallels to the clinical pharmacology of schizophrenia. PMID- 7871037 TI - Subjective and behavioral effects of diazepam depend on its rate of onset. AB - This study addressed the assumption that rate of onset affects the euphorigenic effects of drugs. Drugs with rapid onset are commonly thought to be more euphorigenic than drugs with slower onset, but this idea has rarely been studied directly. Nine healthy male social drinkers, with no history of drug- or alcohol related problems, participated in three sessions. On each session they received oral doses of placebo (PLAC), diazepam in a rapid onset condition (FAST), or diazepam in a slow onset condition (SLOW). In the FAST condition, they received a single 20 mg dose, whereas in the SLOW condition they received six 4 mg doses administered at 30-min intervals. Plasma levels of diazepam and desmethyldiazepam, subjective effects (including measures of euphoria), psychomotor performance and vital signs were monitored throughout each session. Although the FAST and SLOW conditions led to similar peak plasma levels of drug, the peak was attained earlier in the FAST condition (61 min versus 220 min). Subjects' scores on a measure of euphoria (MBG scale of the ARCI) were significantly higher in the FAST condition compared to the SLOW and PLAC conditions. Subjects exhibited significantly more behavioral signs of intoxication and greater psychomotor impairment in the FAST condition. Sedative effects of the drug were similar in magnitude, but the effects lasted slightly longer in the FAST condition. On several measures diazepam produced similar effects in the two conditions (e.g., ratings of strength of drug effect). These data provide limited support for the notion that a faster rate of onset of drug effects is associated with greater euphoria. PMID- 7871038 TI - Serotonin and genetic differences in sensitivity and tolerance to ethanol hypothermia. AB - Mice have been selectively bred for genetic sensitivity (COLD) or insensitivity (HOT) to acute ethanol-induced hypothermia. COLD mice readily develop tolerance to the hypothermic effects of ethanol (EtOH) when it is chronically administered, while HOT mice do not. A number of studies have implicated serotonergic systems in both sensitivity and the development of tolerance to the hypothermic and ataxic effects of EtOH. In the experiments reported here, we administered the serotonin (5HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) to HOT and COLD mice before the acute and chronic administration of equipotent doses of EtOH. 5,7-DHT lesions significantly reduced (by about 65%) whole brain levels of 5HT in both selected lines. This treatment reduced sensitivity to acute EtOH hypothermia in COLD, but not in HOT mice, and blocked the development of tolerance only in COLD mice. Metabolites of 5HT, norepinephrine, and dopamine were generally increased in hypothalamic and brain stem tissue after acute EtOH injection, but HOT and COLD mice were not differentially susceptible to these effects. These results suggest that genes affecting 5HT systems may mediate some of the differences in response to the hypothermic effects of EtOH characterizing HOT and COLD mice. PMID- 7871039 TI - Naloxone precipitates nicotine abstinence syndrome in the rat. AB - Recently, a rodent model of nicotine abstinence syndrome has been developed based on continuous subcutaneous infusion of nicotine tartrate and observing the frequency of spontaneous behavioral signs following termination of infusion. The observed signs closely resemble those commonly seen in rat opiate abstinence syndrome, raising the possibility that there is an endogenous opioid component in nicotine dependence. The present study demonstrates that the opiate antagonist naloxone can precipitate an abstinence syndrome in nicotine-dependent rats. Fourteen rats were infused for 7 days with 9 mg/kg/day nicotine tartrate in saline via an Alzet osmotic minipump. Fourteen rats were sham-operated and remained nicotine-naive. Half of each group received 4.5 mg/kg naloxone SC immediately before a "blind" 15-min observation, while the other half received saline alone. ANOVA revealed significant nicotine infusion, naloxone injection and interaction effects. Post-hoc analysis showed that the nicotine-infused rats injected with naloxone had significantly more signs than all other groups (P < 0.01). In a second experiment, 2 mg/kg morphine sulfate SC produced a significant (P < 0.01) 91.2% reduction of spontaneous abstinence signs observed 21 h after termination of nicotine infusion. These results are consistent with the hypothesized endogenous opioid component in nicotine dependence and abstinence syndrome. PMID- 7871040 TI - Functional consequences of acute cocaine treatment depend on route of administration. AB - The 2-[14C]deoxyglucose method was used to compare the effects of the acute administration of cocaine by two different routes, intravenous and intraperitoneal, on rates of local cerebral glucose utilization in freely moving rats. Doses were initially chosen on the basis of their ability to elicit equivalent increases in locomotor activity during the experimental procedure, and the time of cocaine administration relative to 2-[14C]deoxyglucose infusion was chosen so that the maximal behavioral effect occurred during maximal tracer incorporation. Changes in glucose utilization following the intraperitoneal administration of cocaine (10 mg/kg, 10 min before 2-deoxyglucose infusion) were restricted to the nigrostriatal system and related structures involved in the production of movement. Increased activity was observed in the substantia nigra pars reticulata, globus pallidus, and sensorimotor cortex. In contrast, intravenous cocaine administration (1 mg/kg, 2 min before tracer infusion) produced more widespread changes in rates of glucose utilization including portions of both the mesocorticolimbic and nigrostriatal systems. Areas in which metabolic activity was altered included the caudate-putamen, globus pallidus, substantia nigra pars reticulata, sensorimotor cortex, olfactory tubercle, nucleus accumbens, and medial prefrontal cortex. Both intravenous and intraperitoneal cocaine produced similar increases in locomotor activity. Additional studies indicated that the absence of metabolic activation in the mesocorticolimbic system following acute intraperitoneal cocaine was not the result of the specific dose chosen or the length of time between cocaine administration and radiotracer infusion, as no changes in metabolic activity in mesocorticolimbic structures were evident when these parameters were varied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871041 TI - Voluntary consumption of morphine in 15 inbred mouse strains. AB - To determine genetic differences in voluntary morphine consumption, 15 commonly used inbred strains of mice were given ad libitum two-bottle choice between saccharin alone or saccharin/morphine in one bottle and water in the other bottle. Subsequently, the saccharin was gradually reduced to zero, leaving only morphine. Independent groups of mice of the same strains were exposed to quinine in a parallel manner to control for the bitter alkaloid taste of morphine. Of the 15 strains, the C57BL/6J strain showed the highest consumption of morphine, both with or without saccharin and greatest consumption of morphine relative to quinine; it also showed only a slight decline in fluid consumption when morphine was added to the saccharin bottle. In marked contrast, the SWR/J strain showed the least consumption of morphine by the same criteria, followed closely by the AKR/J, CE/J, DBA/2J and SJL/J strains. The strain differences for all the morphine drinking measures exceeded an order of magnitude. Strain-specific voluntary morphine/saccharin consumption was not significantly correlated with saccharin consumption alone, but was highly correlated with morphine consumption alone. The results show that these behaviors are under an unusually large degree of genetic determination, and some of the largest strain differences remained essentially the same regardless of whether saccharin was present, or whether quinine was used as a control tastant. PMID- 7871042 TI - Caffeine reversal of sleep deprivation effects on alertness and mood. AB - This study assessed the ability of high doses of caffeine to reverse changes in alertness and mood produced by prolonged sleep deprivation. Fifty healthy, nonsmoking males between the ages of 18 and 32 served as volunteers. Following 49 h without sleep, caffeine (0, 150, 300, or 600 mg/70 kg, PO) was administered in a double-blind fashion. Measures of alertness were obtained with sleep onset tests, the Stanford Sleepiness Scale (SSS), and Visual Analog Scales (VAS). Sleep deprivation decreased onset to sleep from a rested average of 19.9 min to 7 min. Following the highest dose of caffeine tested, sleep onset averaged just over 10 min; sleep onset for the placebo group averaged 5 min. Scores on the SSS increased from a rested mean of 1.6-4.8 after sleep deprivation. Caffeine reduced this score to near rested values. Caffeine reversed sleep deprivation-induced changes in three subscales of the POMS (vigor, fatigue, and confusion) and produced values close to fully rested conditions on several VAS. Serum caffeine concentrations peaked 90 min after ingestion and remained elevated for 12 h. This study showed that caffeine was able to produce significant alerting and long lasting beneficial mood effects in individuals deprived of sleep for 48 h. PMID- 7871043 TI - Cocaine administration prior to reactivation facilitates later acquisition of an avoidance response in rats. AB - The effect of cocaine administered prior to memory reactivation on the subsequent acquisition of an avoidance response was investigated. Two noncontingent footshocks were administered to rats in the black compartment of a one-way avoidance chamber. Twenty-four hours later, cocaine or saline was administered 5 min prior to a 30-s reactivation treatment consisting of re-exposure to selected stimuli present during the initial conditioning. Subjects were trained 24 h later to move from the chamber's black compartment to its white compartment in order to avoid a footshock. Intermediate (5.0 or 7.5 mg/kg IP), but not low (3.3 mg/kg IP) or high (11.25 or 16.88 mg/kg IP), doses of cocaine given prior to the reactivation treatment enhanced later acquisition of the one-way avoidance response. These results suggest that cocaine administered prior to the reintroduction of cues associated with a conditioning episode can modulate memory processes, and that the dose-response function for this effect is U-shaped. The avoidance performance of rats that received cocaine (5.0 mg/kg IP) 3 h after the reactivation treatment did not differ from that of saline-treated control subjects, suggesting that the conjoint neural activity elicited by cocaine and exogenous retrieval cues is necessary for potentiation of memory retrieval or reconstruction processes. PMID- 7871044 TI - An open study of the pharmacokinetics and the tolerability of raclopride extended release capsules in psychiatric patients. AB - Following a 4-7 day drug-free washout period, eight male inpatients took an extended-release (ER) formulation of raclopride. After the initial 8 mg dose on day 1 of the study, repeated plasma samples were collected over the ensuing 36 h. Subsequently, patients received raclopride 8 mg b.i.d. through day 7, 12 mg b.i.d. through day 14, and, if tolerated, 16 mg b.i.d. through day 21. On days 7, 14, and 21, repeated plasma samples were drawn over the 12 h following the morning dose. Relative to the previously studied immediate release form of raclopride, the ER formulation delayed and extended the absorption of raclopride, and produced lower maximum raclopride concentrations. Linear kinetics were preserved across the dose range studied. Two patients could not tolerate the highest raclopride dose because of extrapyramidal side effects. PMID- 7871045 TI - 5-HT manipulation and dietary choice: variable carbohydrate (Polycose) suppression demonstrated only under specific experimental conditions. AB - The effects of six 5-HT anorectic agents, d-fenfluramine (5-HT releaser and reuptake inhibitor), fluoxetine (5-HT reuptake inhibitor), mCPP (5-HT1B/5-HT1C receptor agonist), RU24969 (5-HT1A/5-HT1B receptor agonist), MK212 (5-HT1C receptor agonist) and DOI (5-HT2/5-HT1C receptor agonist), and two non-5-HT anorectic agents, salbutamol (beta 2-adrenergic agonist) and d-amphetamine (catecholaminergic agonist), were examined in an experimental procedure designed to disclose selective effects on carbohydrate consumption. In this procedure, a revised version of what we have termed "The Classic Sclafani Paradigm", animals are presented with powdered Polycose as an optional carbohydrate supplement to hydrated chow (nutritionally complete diet). All drugs produced significant reductions in total (hydrated chow plus powdered Polycose) intake. However, only the 5-HT drugs DOI and fluoxetine exerted significantly stronger anorectic effects on intake of powdered Polycose than on intake of hydrated chow. d Fenfluramine also showed a tendency to selectively suppress Polycose intake but this effect marginally failed to reach significance. These results suggest that when experimental conditions are favourable, what appears to be selective carbohydrate (Polycose) suppression can be demonstrated with certain 5-HT drugs. They also suggest that a selective effect on carbohydrate intake is not the most prominent feeding response to 5-HT drugs. PMID- 7871046 TI - Dose dependent effects of alcohol on visual evoked potentials. AB - The effects of various alcohol doses on components of the visual evoked potential were investigated. Using a repeated measures, Latin square design, five alcohol dose conditions were administered to ten male subjects: 0.00 (placebo); 0.28; 0.36; 0.54 and 0.72 g/kg total body weight. EEG responses to a reversing checker board stimulus were measured in a standard oddball paradigm. In the alcohol conditions, latencies of the P1 and P2 components of the VEP were unaffected. However, reaction time, and the latencies of N2 and P3 displayed significant dose related increases with increasing blood alcohol levels. Further, RMS power of the P3 complex was reduced by higher alcohol doses, as was the N2-P3 amplitude difference at central and parietal sites. It is concluded that the latency and power of the endogenous components of the VEP are altered by alcohol, without effects being seen in earlier components. PMID- 7871048 TI - On the preferential release of dopamine in the nucleus accumbens by amphetamine: further evidence obtained by vertically implanted concentric dialysis probes. AB - Concentric dialysis probes were vertically implanted in rats in the nucleus accumbens (Acc) of one side and in the dorsal caudate-putamen (CPu) of the other side. On the day after the implant the output of dopamine was monitored and the changes elicited by d-amphetamine sulphate were compared in the two areas. Amphetamine preferentially stimulated dopamine release in the Acc in a wide range of doses (0.25, 0.5, 1.0, 2.0 mg/kg SC) when Acc probes were located in the medial aspect of the Acc. In contrast, no significant differences between the Acc and the dorsal CPu were obtained in response to amphetamine (0.5 mg/kg SC) when Acc probes were located about 0.7 mm lateral to the previous site. It is concluded that the preferential effect of amphetamine in the Acc is related to precise topographical boundaries. This in turn might be related to the existence of a sharp anatomical and functional heterogeneity within the Acc. PMID- 7871047 TI - Chronic treatment with the D1 receptor antagonist, SCH 23390, and the D2 receptor antagonist, raclopride, in cebus monkeys withdrawn from previous haloperidol treatment. Extrapyramidal syndromes and dopaminergic supersensitivity. AB - The effects of chronic treatment with dopamine (DA) D1 and D2 receptor antagonists were evaluated in eight cebus apella monkeys with mild oral dyskinesia after previous haloperidol treatment. SCH 23390 (D1 antagonist) was given daily to investigate the direct behavioural effect during long-term treatment and the subsequent supersensitivity to DA agonists. Raclopride (D2 antagonist) was investigated for comparison. All drugs were given subcutaneously. SCH 23390 and raclopride induced dystonic syndromes, catalepsy, sedation and reduced locomotor activity. The monkeys developed marked tolerance to the dystonic effect of SCH 23390, while they showed increased sensibility to the dystonic effect of raclopride. Baseline oral dyskinesia (24 h after injection) remained unchanged during D1 antagonist treatment, while it increased during D2 antagonist treatment. SCH 23390 induced supersensitivity to the oral dyskinesia- and grooming-inducing effects of SKF 81297 (D1 agonist) after 9 weeks, while the subsequent treatment with raclopride induced supersensitivity to the reactivity- and stereotypy-inducing effects of quinpirole (D2 receptor agonist) after 3 weeks. Because of the possibility of a carry-over effect (SKF 81297-induced oral hyperkinesia and grooming), other changes in raclopride-induced behaviours cannot be ruled out. The development of tolerance to the dystonic effect of SCH 23390 and the unchanged baseline oral dyskinesia during SCH 23390 treatment indicate an advantageous profile of side effects of DA D1 receptor blockade. PMID- 7871049 TI - Chlormethiazole antagonises seizures induced by N-methyl-DL-aspartate without interacting with the NMDA receptor complex. AB - Administration to mice of N-methyl-DL-aspartate (NMDLA; 680-3400 mumol/kg IP) produced a behavioural syndrome of scratching, running, pawing, clonus, loss of righting and tonic convulsions. Measures of latency to appearance of the behaviours and percentage of animals displaying the behaviour (frequency) indicated that the latency to appearance of running behaviour, clonus and tonic convulsions were all dose dependant. Chlormethiazole (155-622 mumol/kg IP) given 15 min before NMDLA (3400 mumol/kg) dose-dependently inhibited all the behaviours, increasing the latency to appearance of scratching, running and clonus and reducing the incidence of pawing, loss of righting and tonic convulsions. Tonic seizures induced by NMDLA (3400 mumol/kg) were inhibited by the following drugs (ED50 values in mumol/kg in brackets): chlormethiazole (210); pentobarbitone (67); dizocilpine (0.9). The diazepam value (38) was estimated as complete inhibition was not obtained. Chlormethiazole (1 mM) did not affect the binding of [3H]-dizocilpine to rat cortical membranes or the stimulation of this binding by glutamate (10 microM), glycine (10 microM) or spermidine (100 microM). It is therefore concluded that whilst chlormethiazole effectively antagonises the convulsive behavioural syndrome induced by injection of NMDLA, it does not do so by interacting with the NMDA receptor complex but more probably by its known interaction with the GABAA receptor complex. PMID- 7871050 TI - A comparison of the acute behavioral effects of triazolam and temazepam in normal volunteers. AB - Two experiments were conducted to assess the acute behavioral effects of triazolam and temazepam in healthy, non-drug abusing men in double-blind, placebo controlled, crossover trials, where all subjects received all possible doses. These drugs were compared to examine allegations that triazolam produces greater behavioral impairment than temazepam. Drug effects were assessed during 4-h sessions using measures of recall, learning, psychomotor performance, and subject ratings assessing drug effects and abuse potential. In experiment 1, triazolam (0.25 and 0.5 mg/70 kg) produced greater behavioral impairment than temazepam (15 and 30 mg/70 kg). However, triazolam also produced greater increases than temazepam in subject ratings of drug strength, drunkenness and sleepiness, suggesting the dose ranges compared may not have been clinically equivalent. Experiment 2 was conducted to assess whether a higher dose of temazepam than tested in experiment 1 would produce levels of behavioral impairment comparable to those observed with triazolam in experiment 1. In experiment 2, the temazepam dose was increased to 60 mg/70 kg while the triazolam dose was 0.5 mg/70 kg which was the highest dose tested in experiment 1. These doses produced comparable increases in subject ratings of drug strength, drunkenness and sleepiness, but temazepam produced significantly more behavioral disruption than triazolam. These findings do not support the position that triazolam produces greater behavioral impairment than temazepam, and may even suggest that across a wide range of doses triazolam is less disruptive than temazepam. PMID- 7871051 TI - Phenserine: a physostigmine derivative that is a long-acting inhibitor of cholinesterase and demonstrates a wide dose range for attenuating a scopolamine induced learning impairment of rats in a 14-unit T-maze. AB - Phenserine ((-)-N-phenylcarbamoyl eseroline), a carbamate analog of physostigmine (Phy), is a long-acting inhibitor of cholinesterase. We have assessed the potential clinical value of phenserine for cholinomimetic therapy of cognitive impairments associated with aging and Alzheimer's disease by evaluating its duration of in vivo activity against rat plasma acetylcholinesterase (AChE) and its effect on attenuating a scopolamine-induced impairment in learning performance of young rats in a shock-motivated 14-unit T-maze. Phenserine achieved maximum AChE inhibition of 73.5% at 5 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, 69, 3-month-old male Fischer-344 rats were pretrained in a straight runway to avoid electric footshock. On the following day, each animal received 15 trials in the 14-unit T-maze. Sixty minutes prior to the maze training, each rat received the first IP injection of either vehicle (Tween 80, ethanol and 0.9% NaCl) or phenserine at 1.5, 3.0, 4.0, 5.0, 7.5, or 10.0 mg/kg. Then 30 min prior to the training, each animal received a second IP injection of either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg; SCOP). Compared to the vehicle-SCOP group, all but the 7.5 mg/kg dose of phenserine significantly ameliorated error performance, runtime, shock frequency and shock duration in SCOP-treated rats at the final block of three trials. Appearing to have a long effect and a wide therapeutic window, phenserine deserves further study as a cognitive enhancer. PMID- 7871053 TI - Electromyographical differentiation of the components of perioral movements induced by SKF 38393 and physostigmine in the rat. AB - Facial electromyography (EMG) coupled with visual observation was used to investigate spontaneous and drug induced perioral movements in freely moving rats. Four separate perioral behaviours were identified; facial tremor, purposeless chewing, gaping and yawning. Facial tremor, yawning and gaping but not purposeless chewing produced characteristic EMG signals. Normal rats displayed a low level of purposeless chewing, occasional bursts of facial tremor but not gaping or yawning. Each burst of facial tremor was accompanied by a transient increase in purposeless chewing. Administration of the D1 agonist SKF 38393 induced a dose related increase in bursts of facial tremors and consequently an increase in the total number of purposeless chews. Gaping and yawning were not induced by SKF 38393 administration. Administration of the cholinesterase inhibitor physostigmine (0.1-0.4 mg/kg) induced a dose related increase in the total number of purposeless chews, but primarily these were not associated with facial tremor. Administration of physostigmine also increased gaping and yawning. Administration of the D1 antagonist SCH 23390 almost abolished facial tremor in normal treated rats but only partially reduced that induced by SKF 38393 and physostigmine. SCH 23390 reduced purposeless chewing in SKF 38393 treated rats but not in normal or physostigmine treated animals. Administration of the cholinergic antagonist atropine almost abolished facial tremor in normal and physostigmine treated rats, but only reduced by 46% that induced by SKF 38393. Atropine reduced purposeless chewing in normal, physostigmine and SKF 38393 treated animals. Physostigmine induced gaping and yawning were abolished by atropine administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871052 TI - Memory improvement without toxicity during chronic, low dose intravenous arecoline in Alzheimer's disease. AB - Arecoline, a cholinergic agonist, administered at low doses by continuous intravenous infusion for up to 2 weeks, significantly and replicably improved memory in five of nine subjects with mild-moderate Alzheimer's disease. During dose finding, performance on a verbal memory task improved with an inverted U shaped relation to dose. Six of nine subjects were classified as responders. During blinded, placebo-controlled, individualized optimal dosing for 5 days, verbal memory again improved in five of six responders but not in any non responder. No adverse drug effects occurred. Arecoline, and possibly other cholinergic agonists, can safely improve memory in Alzheimer's disease at doses much lower than previously studied. PMID- 7871054 TI - Effect of chronic trifluoperazine administration and subsequent withdrawal on the production and persistence of perioral behaviours in two rat strains. AB - The effect of chronic administration of trifluoperazine on the perioral movement profile of Wistar and Sprague-Dawley rats was examined. Perioral movements were characterised by visual observations, coupled with electromyographic recording from the masseter muscle. In drug-naive animals from both strains the spectrum of perioral behaviours was essentially identical, primarily consisting of purposeless chewing, accompanied by occasional bursts of facial tremor and teeth chattering, with occasional yawning. Each burst of facial tremor was accompanied by a transient increase in the rate of purposeless chewing. Wistar rats exhibited a higher level of spontaneous purposeless chewing compared to Sprague-Dawley rats. In both strains, chronic administration of trifluoperazine (5 mg/kg per day, PO) for 5 months induced an increase in perioral behaviour, which primarily consisted of enhanced purposeless chewing. In Wistar rats the drug-induced increase in purposeless chewing was accompanied by an increase in the incidence of yawning, with no change in the incidence of either facial tremor or teeth chattering. In contrast, Sprague-Dawley rats displayed a drug-induced increase in purposeless chewing, accompanied by an increase in the incidence of facial tremor and teeth chattering, but not yawning. In Wistar rats withdrawal of trifluoperazine diminished but did not reverse the drug-induced increase in purposeless chewing. Drug withdrawal also precipitated a transient increase in the incidence of facial tremor and teeth chattering, but had no effect on yawning. In Wistar rats, the level of purposeless chewing and the incidence of yawning remained elevated above control levels for at least 13 weeks after drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871056 TI - Differential profile of the CCKB receptor antagonist CI-988 and diazepam in the four-plate test. AB - The cholecystokininB receptor antagonist CI-988 ([R-(R*,R*)]-4-[[2-[[3-(1H-indol 3-yl)-2-methyl-1-oxo-2- [[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]amino]- propyl]amino]-1-phenylethyl]amino]-4-oxobutanoic acid compound with 1-deoxy-1 (methylamino)-D-glucitol (1:1)) and the benzodiazepine receptor agonist diazepam were tested for potential anxiolytic effects on punished exploratory behavior in the four-plate test using mice. Diazepam (0.31-5 mg/kg PO) increased the number of shocks taken in a dose-dependent manner, an effect blocked by the benzodiazepine receptor antagonist flumazenil. CI-988 (0.00001-1 mg/kg PO) tended to increase the number of delivered shocks over the chosen dose range; this effect was, however, not dose-related or as large as that produced by diazepam. A limited testing of the 5-hydroxytryptamine3 receptor antagonist ondansetron (0.1 and 1 mg/kg PO) suggested an effect similar to CI-988. These results indicate that distinct and contrasting dose-response profiles exist for these classical and atypical drugs in an animal model of anxiety based on electric shock. PMID- 7871055 TI - Cocaine binding sites in fetal rat brain: implications for prenatal cocaine action. AB - Binding of [3H]cocaine to membrane preparations from whole fetal rat brain was studied. High-affinity binding (10 nM cocaine) was detected as early as gestational day (GD) 15 and steadily increased across subsequent development. Saturation studies comparing [3H]cocaine binding at GD20 and adulthood yielded similar KD values, and LIGAND analyses favored a two-site model if an extended range of [3H]cocaine concentrations was used. Various monoamine uptake inhibitors displaced labeled cocaine with potencies consistent with the idea that [3H]cocaine labels the dopamine (DA), serotonin (5-HT), and possibly also the norepinephrine (NE) transporters in whole fetal brain preparations. Synaptosomal DA uptake was well developed by GD20, as was the potency of cocaine to inhibit such uptake. The results indicate that functional, monoamine transporter related cocaine binding sites are present in the fetal rat brain. Such sites are likely to play an important role in mediating the direct interactions of prenatally administered cocaine with developing monoaminergic systems in both animals and humans. PMID- 7871057 TI - Dissociation of benzodiazepine-induced amnesia from sedation by flumazenil pretreatment. AB - The human amnestic syndrome associated with lesions of the hippocampus and amygdala is characterized by a selective impairment of recent (explicit, episodic) memory. Benzodiazepine (BZ) treated normal subjects demonstrate similar, marked impairments in episodic memory, but in addition, BZ also induces sedation and inattention. Thus, the amnestic effects of BZ may be secondary to drug-induced sedation. However, when subjects were pretreated with the specific BZ receptor antagonist, flumazenil, the sedative and attentional effects of diazepam were blocked, but a marked impairment in episodic memory still occurred. This demonstrates that, using neuropharmacological methods, it is possible to produce a dissociation of memory impairment from inattention and sedation. Such distinct patterns of cognitive dysfunction may serve as models for clinical cognitive syndromes. PMID- 7871058 TI - Ritanserin attenuates anorectic, endocrine and thermic responses to d fenfluramine in human volunteers. AB - This study investigated the role of the 5-HT2/1C receptor antagonist ritanserin on d-fenfluramine (d-FF) induced changes in food intake, prolactin (PRL) secretion and oral temperature in 12 healthy male volunteers. The study was double blind and placebo controlled. Food intake was measured using an automated food dispenser. d-FF (30 mg) significantly reduced fat intake. While ritanserin (5 mg) had no effect when given alone it abolished the d-FF induced reduction in fat intake. In addition, ritanserin abolished the d-FF induced rise in PRL and oral temperature. The results suggest that 5-HT2 or 5-HT1C receptors mediate the effects of d-fenfluramine on appetite, prolactin secretion and temperature in humans. PMID- 7871059 TI - Influence of tetrodotoxin and calcium on changes in extracellular dopamine levels evoked by systemic nicotine. AB - The influence of tetrodotoxin (TTX) and calcium on the increase of extracellular dopamine (DA) levels in the nucleus accumbens (NAcc), evoked by the systemic administration of nicotine, cocaine and d-amphetamine, have been studied in conscious, freely moving rats using in vivo microdialysis. TTX (10(-6) M), administered via the dialysis probe, completely abolished (P < 0.01) the elevations in extracellular DA, DOPAC and HVA seen following nicotine (0.4 mg/kg SC). The removal of calcium with the inclusion of diaminoethanetetraacetic acid (EDTA 10(-4) M) in the Ringer solution was also associated with inhibition (P < 0.01) of the nicotine-induced changes in these parameters. The systemic administration of cocaine (15 mg/kg IP) and d-amphetamine (0.5 mg/kg SC) caused elevations in extracellular DA (P < 0.01) accompanied by significant decreases (P < 0.01) in HVA levels. DOPAC levels were also significantly (P < 0.01) lowered by d-amphetamine treatment. The presence of TTX and removal of calcium with addition of EDTA completely abolished the changes in NAcc DA and HVA induced by cocaine. TTX had no influence on the d-amphetamine evoked responses in NAcc DA. However, the metabolites, which were markedly reduced by the TTX, were not further decreased by the systemic administration of d-amphetamine. NAcc DA was significantly (P < 0.01) raised following d-amphetamine in the absence of calcium and presence of EDTA. However, this was significantly (P < 0.01) attenuated in comparison to that seen in the presence of calcium. The results support the conclusion that, at the dose tested, nicotine evokes increases in extracellular NAcc DA levels by calcium and impulse-dependent mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871060 TI - A comparison of the effect of lorazepam on memory in heavy and low social drinkers. AB - The cognitive deficits, particularly memory impairment, observed in association with organic brain damage caused by chronic alcohol ingestion, are consistent with the profile of benzodiazepine-induced amnesia. This study examined the cognitive capabilities of a group of heavy social drinkers (n = 11) and a group of low social drinkers (n = 11) under the influence of a pharmacological challenge (lorazepam 2 mg) and a placebo treatment. Lorazepam impaired visual memory and verbal learning in both groups, but the effect of lorazepam was exacerbated in the heavy social drinkers for delayed recall of verbal material. Heavy social drinkers had lower verbal fluency scores and were less able to copy complex figures than low social drinkers whether or not the pharmacological challenge was present. Lorazepam induced deficits, in both groups, which confirmed to the classic profile of those observed in benzodiazepine-induced amnesia. The deficits, both in the absence and presence of lorazepam, shown by heavy social drinkers suggest that changes may have occurred in their brain functioning. PMID- 7871061 TI - MAO inhibitors in panic disorder: clinical effects of treatment with brofaromine. A double blind placebo controlled study. AB - There is considerable evidence that antidepressants, particularly serotonin uptake inhibitors, are effective in the treatment of panic disorder (PD). Monoamine oxidase inhibitors (MAOI) may also have beneficial effects in PD. In this study 30 patients with PD with or without agoraphobia (DSM-III-R) were treated with the selective and reversible MAO-A inhibitor brofaromine (150 mg daily) in a 12-week double-blind placebo controlled design. A clinical relevant improvement was found in more than 70% of the patients treated with brofaromine, whereas no significant improvement was observed on placebo. After an increase in anxiety in the first week, a clinically relevant improvement in anxiety symptoms was found, followed by a subsequent reduction in agoraphobic avoidance in patients treated with brofaromine. A similar improvement was observed on distress scores related to panic attacks, although there was no significant reduction in the number of panic attacks. The most prominent side-effects were middle sleep disturbance and nausea. No increase in blood pressure was observed. During a follow-up period of another 12 weeks a further improvement was found in patients treated with brofaromine. PMID- 7871062 TI - Effect of pharmacological daytime doses of melatonin on human mood and performance. AB - Melatonin (10, 20, 40, or 80 mg, PO) or placebo was administered at 1145 hours on five separate occasions to 20 healthy male volunteers and the effects on serum melatonin levels, mood, performance, and oral temperature were monitored. Subjects were studied between 0930 and 1700 hours. A battery of interactive computer tasks designed to assess performance and mood was completed, oral temperature was measured, and blood samples were taken for serum melatonin radioimmunoassay. The areas under the time-melatonin concentration curve (AUC) varied significantly in proportion to the various melatonin doses. Compared with placebo treatment, all melatonin doses significantly decreased oral temperature, number of correct responses in auditory vigilance, response latency in reaction time, and self-reported vigor. Melatonin also increased self-reported fatigue, confusion, and sleepiness. PMID- 7871064 TI - Voluntary consumption of ethanol in 15 inbred mouse strains. AB - To determine genetic differences in ethanol consumption, 15 commonly used inbred strains of mice were given ad libitum two-bottle choice between ethanol, 0.2% saccharin, or ethanol plus saccharin in one bottle versus tap water in the other bottle. Three different concentrations of ethanol were used: 3%, 6% and 10% (v/v). Of the 15 strains, the C57BL/6J, C57BR/cdJ and C57L/J strains showed the most consistent higher intake of ethanol either with or without 0.2% saccharin. In marked contrast, the DBA/1J and DBA/2J strains consistently showed the lowest intake. Consumption of 3% ethanol without saccharin was highly genetically correlated with saccharin consumption (r = 0.77), suggesting that low concentrations of ethanol may have a sweet taste that affects voluntary consumption. Most strains showed very different patterns of response to ethanol with or without saccharin. Three patterns of strain responses were identified. Some strains avoided higher concentrations of ethanol whether in water or saccharin; some appeared to be sensitive to the ability of saccharin to mask the odor of ethanol; and some may have reduced consumption only when ethanol concentrations were high enough to produce aversive postingestional effects. Whereas earlier studies generally attempted to explain strain differences in consumption by invoking a single mechanism, our results demonstrate that more than one mechanism is necessary to explain the preferential ethanol intake of all strains studied. PMID- 7871063 TI - Monoamine uptake inhibitors alter cocaine pharmacokinetics. AB - The time course of change in plasma levels of cocaine and its major metabolite benzoylecgonine following 3 mg/kg IV cocaine and the pharmacokinetic interaction between cocaine and several monoamine uptake inhibitors were investigated in conscious rats implanted with arterial and venous cannulae. The IV bolus administration of 3 mg/kg cocaine resulted in plasma levels of 1276 +/- 53 ng/ml cocaine at 0.5 min following its injection and the levels then rapidly declined to 768 +/- 110 ng/ml by 2 min. Thereafter, the decline of plasma cocaine levels was relatively slow. Plasma benzoylecgonine levels were similar at 0.5 and 2 min following cocaine injection but increased gradually over the next 25 min. Pretreatment with the norepinephrine-selective uptake inhibitors desipramine and nisoxetine, the serotonin-selective uptake inhibitor fluoxetine or the dopamine selective uptake inhibitor GBR 12909 all enhanced plasma levels of cocaine after a 3 mg/kg IV bolus injection at 0.5, but not at 5 min after injection. The enhancement of plasma cocaine levels by GBR 12909 was of greater magnitude than that produced by desipramine, nisoxetine or fluoxetine. These agents, with the exception of the high dose (10 mg/kg) of GBR 12909, did not significantly alter plasma levels of benzoylecgonine measured at either 0.5 or 5 min following cocaine injection. These results indicate that monoamine uptake inhibitors can alter or interfere with the pharmacokinetics of cocaine and that this interaction is not due to a change in the biotransformation of cocaine. It is suggested that the central monoamine uptake sites serving as rapid distribution sites for cocaine may play a role in this pharmacokinetic interaction. PMID- 7871065 TI - Opioid physical dependence development in humans: effect of time between agonist pretreatments. AB - We examined the effect of morphine pretreatment spacing on intensity of subsequent precipitated withdrawal response to test the hypothesis that withdrawal intensity would be inversely related to pretreatment spacing. Subjects were ten nondependent male volunteers who reported using opioids an average of 2.5 times per week. Three IM morphine injections (each 18 mg/70 kg) were administered during each of four experimental conditions. The experimental conditions involved spacing injections at 12-, 24-, 48- or 72-h intervals. Naloxone (10 mg/70 kg IM) was administered 24 h after the last morphine exposure. A comparison condition was included in which a naloxone challenge was given at 24 h following a single IM morphine pretreatment (18 mg/70 kg). Subject rated measures of symptoms and observer-rated measures of signs indicated that withdrawal intensity was inversely related to the morphine spacing interval and in particular that intensity of withdrawal precipitated after three pretreatments spaced at 12-h intervals was greater than that precipitated after a single morphine pretreatment. Physiological data supported a more intense withdrawal response in the 12-h spacing condition and provided evidence of overshoot on blood pressure and skin temperature measures. These findings are pertinent to the transition between acute and chronic physical dependence; they suggest that there is a temporal window during which repeated opioid administrations result in escalation of physical dependence but that dependence levels after widely spaced multiple exposures may be no greater than after a single exposure. PMID- 7871066 TI - Raclopride, but not SCH 23,390, induces maldirected jumping in rats trained to perform a run-climb-run behavioral task. AB - In order to explore further the putative differential behavioral consequences of D1 dopamine and D2 dopamine receptor antagonism, SCH 23,390 (0.01-0.12 mg/kg) and raclopride (0.12-1.0 mg/kg) were administered to two separate groups of rats that had been trained in an eight-trial-per-day format to run down an alleyway, climb a vertical rope, and run across a horizontal board to access sweetened milk. Although both drugs dose-dependently reduced the speed of task completion, only raclopride produced vigorous, maldirected jumping behavior in the floor segment of the apparatus. The number of such jumps increased with dose. This raclopride specific jumping phenomenon may provide a new behavioral arena for investigating the functional differences between D1 and D2 receptor antagonism. PMID- 7871067 TI - Evaluation of the discriminative stimulus effects of the novel sedative-hypnotic CL 284,846. AB - CL 284,846, N-[3-(3-cyanopyrazolo[1, 5-a]pyrimidin-7-yl)phenyl)]-N- ethylacetamide, is a novel non-benzodiazepine sedative-hypnotic with benzodiazepine-like sedative effects, but with less apparent liability for accompanying undesired side effects. In an effort to further characterize its pharmacological activity, CL 284,846 (3.0 mg/kg, IP, 30 min pretreatment) was established as a discriminative stimulus (DS) in rats (n = 7). CL 284,846 (0.3 10.0 mg/kg) showed a dose-related increase in drug-appropriate responding up to the training dose and a dose-related decrease in response rate. The benzodiazepine agonist triazolam (0.1-1.0 mg/kg), the benzodiazepine partial agonist Ro 17-1812 (0.3-3.0 mg/kg) and the triazolopyridazine CL 218,872 (1.0-3.0 mg/kg) substituted for CL 284,846 in all rats, whereas the imidazopyridines zolpidem (3.0-10.0 mg/kg) and alpidem (10.0-30.0 mg/kg), the benzodiazepine partial agonist bretazenil (0.03-10.0 mg/kg) and the novel putative anxiolytic CL 273,547 (10.0-56.0 mg/kg) substituted in most, but not all, rats. Ro 17-1812, bretazenil, and CL 218,872 had no effect on response rate while the other drugs showed a concomitant decrease in rate. The 5-HT1A agonist buspirone (1.0-10.0 mg/kg) and the barbiturate pentobarbital (3.0-17.0 mg/kg) failed to substitute for CL 284,846 up to rate-decreasing doses. The benzodiazepine antagonist flumazenil (3.0-10.0 mg/kg) blocked the DS effects of CL 284,846 in most rats with no effect on response rate. Taken together, these results suggest that the DS effects of CL 284,846 are mediated via benzodiazepine receptors; however, the DS profile of CL 284,846 remains distinct from both benzodiazepine and non benzodiazepine sedative-hypnotic drugs. PMID- 7871069 TI - Cocaine behavioral sensitization and the excitatory amino acids. AB - Studies were conducted to identify neuroeffector systems involved in behavioral sensitization to cocaine-induced stereotypy in mice, and to compare the results with those from our previous amphetamine studies. The effects of eight relatively selective neuroeffector agonists and antagonists were measured in mice in order to identify specific functional changes associated with the sensitization. In contrast to amphetamine, the only neuroeffector response altered by cocaine sensitization was a decrease in convulsive threshold to kainate. The persistence of the change in convulsive threshold correlated with the persistence of behavioral sensitization. The induction of sensitization was blocked by pretreatment with four different classes of drugs, represented by haloperidol, dizocilpine, diltiazem and DNQX. These results suggest that the mechanism of induction to cocaine is similar to that of amphetamine; both the glutamate and dopaminergic systems appear to be involved in induction. The expression of the sensitized cocaine response was blocked by haloperidol, CPP and diltiazem. These results differed from those obtained previously insofar as CPP did not affect the expression of sensitization to amphetamine. Furthermore, DNQX, in contrast to its antagonism of the expression of amphetamine sensitization, did not affect the expression of cocaine sensitization. The pharmacological data suggest that the mechanism of induction differs from that of expression, and that the mechanism of expression for cocaine sensitization differs from that for amphetamine. PMID- 7871068 TI - Alterations in striatal acetylcholine overflow by cocaine, morphine, and MK-801: relationship to locomotor output. AB - The activity of cholinergic interneurons in the striatum appears to be modulated by a variety of different systems including dopamine, opiate, and glutamate. The purpose of this study was to characterize the effects of drugs known to act on these three systems (i.e., cocaine, morphine, and MK-801) on striatal ACh overflow with microdialysis procedures, and to determine if alterations in ACh function induced by these agents are related to changes in locomotor activity. Cocaine was found to increase striatal ACh following intraperitoneal injections of 20 and 40 mg/kg, but not 10 mg/kg. The increases in locomotor activity induced by cocaine appeared to be dose dependent, while the effects on striatal ACh were not. Injections of 0.1 mg/kg MK-801 (a non-competitive NMDA receptor antagonist) produced dramatic increases in locomotor activity while decreasing striatal ACh overflow. A lower dose (0.03 mg/kg) of MK-801 failed to alter locomotor activity or striatal ACh. Morphine produced an apparent dose-dependent elevation in striatal ACh while only the lowest dose (5 mg/kg) increased locomotor activity. There appears to be no relationship between alterations in striatal ACh and locomotor output following systemic administration of these psychoactive agents. PMID- 7871070 TI - Differential effects of systemically administered nor-binaltorphimine (nor-BNI) on kappa-opioid agonists in the mouse writhing assay. AB - The opioid antagonist effects of systemically administered nor-binaltorphimine (nor-BNI) were evaluated against the kappa agonists CI-977, U69,593, U50,488, ethylketocyclazocine (EKC), Mr2034 and bremazocine, the mu agonist morphine and the alkaloid delta agonist BW-373U86 in the acetic acid-induced writhing assay in mice. All eight agonists completely and dose-dependently inhibited writhing. Antagonism of CI-977 was apparent 1 h after administration of 32 mg/kg nor-BNI, peaking after 4 h and was maintained for at least 4 weeks; no antagonist effects of nor-BNI were apparent after 8 weeks. Nor-BNI (32 mg/kg) caused little or no antagonism of morphine or BW-373U86 at 1 h and none at 24 h after nor-BNI administration. Subsequently, dose-effect curves for CI-977, U50,488, U69,593, EKC, Mr2034 and bremazocine were determined 24 h after pretreatment with 3.2, 10 and 32 mg/kg nor-BNI. Pretreatment with 3.2 mg/kg nor-BNI produced significant antagonism of all six kappa agonists, suggesting that their antinociceptive effects were mediated at least in part by nor-BNI-sensitive kappa receptors. At higher doses, nor-BNI dose-dependently shifted the agonist dose-effect curves of CI-977, U50,488, U69,593 and bremazocine, but not those of EKC and Mr2034, suggesting that the latter compounds may be producing effects via nor-BNI insensitive receptors. Mu receptor involvement was demonstrated following a 24 h pretreatment with 32 mg/kg beta-FNA in combination with nor-BNI, which significantly increased the degree of antagonism of Mr2034 and EKC from that seen with nor-BNI alone.2+ off PMID- 7871071 TI - Caffeine augmentation of electroconvulsive seizures. AB - Caffeine has been used clinically to increase seizure length in electroconvulsive treatment (ECT). The present study was designed to establish an animal model of caffeine-augmented seizures for further study of mechanisms and effects of pharmacological manipulation of seizure length. Increasing doses of caffeine (0 200 mg/kg, IP) were given before electroconvulsive stimulation (ECS) in rats and resulting seizure lengths were quantified by timing of classical tonic-clonic convulsive movements. With this paradigm, caffeine led to a dose-dependent increase in seizure duration. This proconvulsant action of caffeine was detectable within 1 min after dosing, persisted for at least 230 min and was reversible. The results suggest that seizure length is a practicable measure in pharmacological modification of electroconvulsive seizures. They also suggest that pharmacologically-modified ECS can be modeled effectively in animals. PMID- 7871072 TI - The benzodiazepine inverse agonist RO19-4603 exerts prolonged and selective suppression of ethanol intake in alcohol-preferring (P) rats. AB - The time course of the benzodiazepine (BDZ) inverse agonist RO19-4603 in antagonizing ethanol (EtOH) intake was investigated in alcohol-preferring (P) rats (n = 7) maintained on 24-h continuous free-choice access to EtOH (10% v/v), water, and food. After fluid intakes had stabilized over several weeks, animals were injected with Tween-80 vehicle solution or RO19-4603 (0.075, 0.150, and 0.30 mg/kg). EtOH and water intakes were determined at 8- and 24-h intervals. RO19 4603 caused a marked attenuation of EtOH drinking with each of the doses tested. EtOH intake during the 8-h following 0.075, 0.150, and 0.30 mg/kg RO19-4603 was decreased by approximately 36, 74, and 57%, respectively. Intakes during the 24-h interval were similar to the vehicle control condition. However, 32 h post-drug administration, EtOH intakes were reduced to approximately 27, 31, and 29% following the 0.075, 0.150 and 0.30 mg/kg doses, respectively. To further confirm the reliability of the RO19-4603 dose-response effect, and its selectivity for EtOH, the highest dose condition (0.30 mg/kg) was tested twice. The second 0.30 mg/kg dose condition exerted a profile of effects similar to the initial treatment; 8 h following administration, intake was decreased to 60% of the control level, and 32 h post-drug administration intake was decreased to approximately 46% of the controls. These decreases were evidently selective in comparison with water, since water drinking showed compensatory increases which paralleled the decreased EtOH consumption. Dose-response comparisons indicated that 0.150 mg/kg approaches the maximum effective dose, since the 0.30 mg/kg dose of RO19-4603 did not produce an additional decrease in EtOH intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871073 TI - Ethanol self-administration in freely feeding and drinking rats: effects of Ro15 4513 alone, and in combination with Ro15-1788 (flumazenil). AB - Recent work in our laboratory demonstrated that Ro15-4513, a partial inverse benzodiazepine (BDZ) agonist, decreases ethanol (ETOH) self-administration in rodents under fluid deprivation conditions. The present study further examined the effects of Ro15-4513 (2.5 and 5.0 mg/kg) alone and in combination with Ro15 1788, (flumazenil) (8.0 and 16.0 mg/kg), a BDZ receptor antagonist on ETOH self administration in freely feeding and drinking rats. Animals were trained to consume ETOH (11% v/v) using a limited access procedure. Measurements were taken at 10- and 60-min intervals. Ro15-4513 (2.5 and 5.0 mg/kg) markedly attenuated ETOH consumption at both intervals. The antagonistic actions of Ro15-4513 were completely blocked by the higher dose of flumazenil at both intervals; the lower dose failed to antagonize the Ro15-4513-induced reduction of ETOH intake. When flumazenil was given alone, both doses reduced ETOH self-administration at 60 min; although the magnitude of the antagonism was comparable to that of Ro15-4513 only with the highest does of flumazenil (16.0 mg/kg). Neither Ro15-4513 nor flumazenil alone or in combination significantly altered water intake at any of the tested doses. Rats pretreated with Ro15-4513 showed a substantial reduction in blood ethanol concentration (BEC) compared with the Tween-80 vehicle condition at the 10-min interval. However, the BEC of animals given Ro15-4513 in combination with flumazenil were similar to rats given Tween-80 vehicle. The present study extends our previous research by demonstrating that Ro15-4513 and flumazenil attenuate ETOH self-administration in non-food or water deprived rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871074 TI - Acute and residual effects of alcohol and marijuana, alone and in combination, on mood and performance. AB - The duration of behavioral impairment after marijuana smoking remains a matter of some debate. Alcohol and marijuana are frequently used together, but there has been little study of the effects of this drug combination on mood and behavior the day after use. The present study was designed to address these issues. Fourteen male and female subjects were each studied under four conditions: alcohol alone, marijuana alone, alcohol and marijuana in combination, and no active treatment. Mood and performance assessments were made during acute intoxication and twice the following day (morning and mid-afternoon). Acutely, each drug alone produced moderate levels of subjective intoxication and some degree of behavioral impairment. The drug combination produced the greatest level of impairment on most tasks and "strong" overall subjective ratings. There were few significant interactions between the two drugs, indicating that their effects tended to be additive. Only weak evidence was obtained for subjective or behavioral effects the day after active drug treatments, although consistent time of-day effects (morning versus afternoon) were observed on several subjective and behavioral measures. In sum, this study provided little evidence that moderate doses of alcohol and marijuana, consumed either alone or in combination, produce behavioral or subjective impairment the following day. PMID- 7871075 TI - Effects of benzodiazepine receptor ligands on the performance of an operant delayed matching to position task in rats: opposite effects of FG 7142 and lorazepam. AB - The effects of a series of benzodiazepine (BZ) receptor ligands, ranging from a full agonist through to partial inverse agonists, were examined on short term working memory in the rat. The behavioural paradigm used was a discrete trial, operant delayed matching to position task, as originally described by Dunnett (1985), with delays of 0, 5, 15 and 30 s. The benzodiazepine receptor (BZR) full agonist lorazepam (0.25, 0.375 and 0.5 mg/kg) dose and delay dependently impaired matching accuracy. Lorazepam also increased the latency to respond and decreased the number of nose pokes made into the food tray during the delays. In contrast, the BZR partial agonist ZK 95,962 (1, 3, 10 mg/kg) did not affect matching accuracy, but did increase the speed of responding. The BZR antagonist ZK 93,426 (1.25, 5, 25 mg/kg) had no effects in this paradigm. The BZR weak partial inverse agonists Ro 15-4513 (0.1, 1 and 10 mg/kg) and ZK 90,886 (1, 3 and 10 mg/kg) did not affect accuracy of performance. However, both of these drugs increased the latency to respond and decreased nose poke responses. These motoric effects were particularly strong following 10 mg/kg Ro 15-4513. This shows that the effects of drugs on the accuracy of responding and on the speed of responding can be dissociated. The BZR partial inverse agonist FG 7142 had effects on matching accuracy that were dependent upon dose. The lowest dose of FG 7142 (1 mg/kg) significantly improved accuracy, whereas the highest dose (10 mg/kg) impaired accuracy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871076 TI - Psychomotor stimulant effects of d-amphetamine, MDMA and PCP: aggressive and schedule-controlled behavior in mice. AB - The objective of the present experiments was to characterize psychomotor stimulant effects of d-amphetamine, methylenedioxymethamphetamine (MDMA) and phencyclidine (PCP) on conditioned performance and on aggressive behavior in mice. In a novel protocol with alternating periods of schedule-controlled responding and aggressive behavior toward an intruder it was possible to assess a range of species-specific agonistic acts, postures, and motor activities as well as response rates and patterns engendered by a multiple Fixed Interval (FI) and Fixed Ratio (FR) schedule within the same animal. Initially, it was confirmed that d-amphetamine and, less reliably, MDMA and PCP, increased FI, but not FR responding in mice. In the next experiment, mice confronted an intruder at the midpoint of the 1-h daily session; following the display of aggressive behavior, the rate of FI responding showed an amphetamine-like increase, whereas only a transient change occurred after non-aggressive encounters. Thirdly, using this new protocol, PCP, d-amphetamine and MDMA altered FI and FR responding in a way that was closely similar to the first experiment. Low PCP and d-amphetamine doses increased aggressive behavior erratically in certain individuals, but not reliably for the group. MDMA dose-dependently decreased aggressive behavior, and all drugs disrupted aggressive behavior at higher doses. The characteristic increases in walking and decreases in rearing after higher doses of PCP and d amphetamine were greatly attenuated when the intruder was present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871077 TI - The intrinsic effects of sarmazenil on sleep propensity and performance level of sleep-deprived subjects. AB - The effect of two dosages of sarmazenil (RO 15-3505) on sleep propensity and performance was investigated in a double-blind, placebo-controlled paradigm. The design included three 24-h testing periods, separated by at least one 7-day rest period, commencing after 24-h of sleep deprivation. Twelve normal, healthy, adult males (mean age 27 +/- 2.8 years) were paid to participate. During the experimental periods, they came to the sleep laboratory at 2100 hours and spent the night awake under close supervision. At 0700 hours, a schedule of 7 min "attempting" sleep in bed, 13 min awake outside the bedroom, began. This schedule was maintained for 24 h. Repeated administrations of 1 mg and 2 mg sarmazenil significantly reduced the 24-h levels of total sleep. This was particularly evident during the period 0700-2300 hours. Sarmazenil also significantly improved reaction time and tended to increase the number of correct responses in the "categories search" task. Sarmazenil tended to improve reaction time in the "Stroop" test but this was significant only for the "easy" version of the test during the night. PMID- 7871078 TI - Effect of chronic lithium treatment with or without haloperidol on number and sizes of neurons in rat neocortex. AB - The present study used stereological methods to determine whether long-term administration of lithium, with or without haloperidol, affects the number and average volume of neocortical neurons. Twenty-five rats were divided into three groups and given no treatment, lithium, or lithium combined with haloperidol. Serum lithium levels ranged from 0.5 to 0.8 mmol/l. Haloperidol was injected intraperitoneally at a daily dose of 1 mg/kg. After 30 weeks of treatment, the animals were killed and the brains were prepared. Neocortical volume, density of neurons, total number of neurons and mean volume of neurons were estimated. As no differences were found between the groups, the present study provides no evidence for quantitative morphological changes in the cerebral cortex due to long-term 'therapeutic' levels of lithium, with or without haloperidol. PMID- 7871079 TI - Effects of cocaine microinjections into the nucleus accumbens and medial prefrontal cortex on schedule-induced behaviour: comparison with systemic cocaine administration. AB - The effects of cocaine HCl infusions into either the nucleus accumbens (NACC) or medial prefrontal cortex (PFC) were compared on the performance of schedule induced polydipsia (SIP) and related behaviours. Food-deprived rats were exposed to a fixed-time 60-s schedule of food delivery in daily 30-min sessions until stable levels of behaviour were obtained (14 days). Rats were then bilaterally infused with cocaine into either the NACC or PFC via chronically indwelling guide cannulae. Each subject received a sequence of five cocaine infusions (0, 12.5, 25, 50, 100 micrograms) according to a Latin Square design. For comparison, following these intracranial infusions each rat received a sequence of five IP injections of cocaine (0, 2.5, 5, 10, 20 mg/kg) also in a counterbalanced order. NACC and PFC infusions of cocaine and IP cocaine dose-dependently reduced SIP. Cocaine infusions into the NACC, but not the PFC, increased locomotor activity but the characteristic temporal profile of locomotor activity during SIP was retained. IP cocaine also increased locomotor activity in a dose-dependent manner, but the temporal profile of activity was flattened following 20 mg/kg cocaine. NACC and PFC infusions of cocaine had little effect on the total number of panel presses to gain access to the food pellets, but did slightly decrease the high rates of responding immediately prior to the pellet delivery. IP cocaine increased the total number of panel presses at the higher doses, mainly by increasing the low rates of responding. The effects of cocaine infusions into the PFC were behaviourally the most selective, as they reduced SIP without having substantial effects either on locomotor activity or panel pressing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871080 TI - The expected drug and its expected effect interact to determine placebo responses to alcohol and caffeine. AB - This study tested placebo responses in psychomotor performance when caffeine or alcohol was expected. Fifty male university students were assigned to one of four placebo groups or to a no-treatment control group. Two groups received placebo caffeine and two received placebo alcohol. Subjects performed 12 trials on a pursuit rotor task and performance was measured by the percent time on target. Then they received information about the expected drug effect on the task. One caffeine placebo group (C+) and one alcohol placebo group (A+) were led to expect enhanced performance on the task. The other caffeine placebo group (C-) and alcohol placebo group (A-) were led to expect impaired performance. Subjects subsequently performed 12 trials on the task. An interaction was obtained between the expected type of effect and the expected type of drug. The C+ group displayed superior performance compared to the C- group, and the reverse relationship was observed between the A+ and A- group. In addition, subjects led to expect alcohol induced impairment (A-) performed better than subjects led to expect caffeine induced impairment (C-). Subjects also reported greater motivation to resist impairment when they expected alcohol rather than caffeine. The research indicates that understanding and predicting placebo responses may require consideration of the drug that is expected as well as its expected effect. PMID- 7871081 TI - Individual differences in stress and arousal during cigarette smoking. AB - Self-rated feelings of stress and arousal were monitored before and after each cigarette, over a day of normal smoking. Subjects comprised 105 unpaid volunteers (65 female, 40 male; mean age 30.4 years; mean consumption 12.4 cigarettes on test day). Feelings of arousal were significantly higher post-smoking than pre smoking. The degree of arousal change was monotonically related to scores on the smoking motivation questionnaire (SMQ) stimulant subscale, with high stimulant smokers reporting the greatest arousal modulation. However stimulant smokers reported low arousal before smoking, rather than high arousal after smoking. Feelings of stress were significantly lower post-smoking than pre-smoking. The degree of stress change was monotonically related to scores on the SMQ sedative subscale, with high sedative smokers reporting the greatest stress change. This confirms the criterion validity of this second SMQ subscale. However, as with the arousal data, sedative smokers tended to report high stress before smoking, rather than low stress after smoking. Smoking did not therefore produce advantageous post-cigarette feeling states. Instead, mood modulation largely comprised the alleviation of poor psychological states prior to smoking. These stress and arousal changes often occurred simultaneously, against the predictions of the arousal modulation theory. Arousal modulation and stress modulation should therefore be seen as separate and independent processes. Lastly, feelings of stress and arousal fluctuated repeatedly over the day, with improved moods immediately after smoking, but impaired moods developing between cigarettes. These mood reversals provide a clear psychological rationale for the repetitive (addictive) nature of nicotine use. PMID- 7871082 TI - Lorazepam and diazepam effects on memory acquisition in priming tasks. AB - Unlike diazepam, lorazepam has repeatedly been shown to impair perceptual priming as well as explicit memory. To determine whether this deleterious effect was due to an impairment in acquisition of information, 60 healthy volunteers were randomly assigned to five treatment groups (placebo, lorazepam 0.026 or 0.038 mg/kg, diazepam 0.2 or 0.3 mg/kg) and successively performed perceptual priming tasks and a free-recall task. Priming performance on information learned before or 2 h after drug administration, i.e. at the peak concentration of lorazepam, was assessed under the influence of the drugs, using a picture-fragment and a word-stem completion task. Free-recall performance was altered by both drugs. Lorazepam decreased priming performance when information was acquired after, but not before, drug administration, indicating that the drug alters the acquisition of information. Lorazepam also impaired the ability to identify fragmented pictures, but there was no evidence that this perceptual effect accounts for the priming impairment. Surprisingly, diazepam also decreased priming when information was acquired after drug administration, suggesting that, at least in certain circumstances, the two benzodiazepines may exert similar effects on priming measures. PMID- 7871083 TI - Isolation rearing enhances the locomotor response to cocaine and a novel environment, but impairs the intravenous self-administration of cocaine. AB - Male Lister hooded rats were raised from weaning either alone (isolation reared) or in groups of five (socially reared controls). At 5 months of age, experiments began. Experiment 1 examined the effect of isolation rearing upon the locomotor response to a novel environment, and the locomotor stimulant effect of an injection of cocaine (10 mg/kg). Isolation reared animals were more active in a novel environment, and were more responsive to the locomotor stimulant action of cocaine. In succeeding experiments, the effects of isolation rearing on the reinforcing efficacy of intravenous cocaine were assessed. Animals were never "primed" with noncontingent infusions of cocaine at any time during these experiments. In experiment 2, the effect of isolation rearing upon the acquisition of the intravenous self-administration of cocaine was examined. Two levers were present in the operant chambers. Depression of one lever resulted in the intravenous delivery of a 1.5 mg/kg infusion of cocaine, responses on the second, control lever were recorded but had no programmed consequences. Isolation reared animals acquired a selective response on the drug lever at a slower rate than socially reared controls. In experiment 3, a full cocaine dose-response function was examined. Isolation rearing shifted the cocaine dose-response function to the right. In addition, isolation rearing impaired the selectivity of the response on the drug lever at lower doses of cocaine. In experiment 4, the effect of isolation rearing upon the response to a conditioned reinforcer associated previously with cocaine delivery was observed. In the absence of cocaine, the contingent presentation of the conditioned reinforcer enhanced selectively the rate of response by socially reared controls. However, isolation reared animals were unresponsive to this manipulation. These data are discussed with reference to dysfunctional cortico-limbic-striatal systems, and their interactions with the mesoaccumbens dopamine projection. PMID- 7871084 TI - Isolation rearing impairs the reinforcing efficacy of intravenous cocaine or intra-accumbens d-amphetamine: impaired response to intra-accumbens D1 and D2/D3 dopamine receptor antagonists. AB - Male Lister hooded rats were raised from weaning either alone (isolation reared) or in groups of five (socially reared controls). At 5 months of age, bilateral guide cannulae were implanted within the nucleus accumbens, and experiments began. The effect of isolation rearing upon the reinforcing efficacy of the intravenous self-administration of cocaine (experiment 1), or the bilateral intra accumbens self-administration of d-amphetamine (experiment 2) was assessed. Self administration was made contingent upon the acquisition of a novel lever-pressing response. Two identical levers were available within each operant chamber. Responding on one lever resulted in the delivery of drug (experiment 1: cocaine, 1.5 mg/kg per infusion; experiment 2: d-amphetamine, 0.25 micrograms/side), responding on the second, control lever was recorded but had no programmed consequences. Animals were not "primed" with noncontingent infusions at any time. For experiment 1, animals received intra-accumbens infusions of the D1 dopamine receptor antagonist SCH-23390, or the D2 dopamine receptor antagonist sulpiride over two test sessions. Within each session, animals received a cumulative series of doses of each dopamine receptor antagonist. A validation group received doses of each antagonist according to more conventional methods (one dose per session). In either case, intra-accumbens infusions of SCH-23390 or sulpiride enhanced the rate of the self-administration of cocaine in socially reared controls. However, isolation rearing impaired this response to intra-accumbens infusions of the dopamine receptor antagonists. Experiment 2a examined the acquisition of the intra-accumbens self-administration of d-amphetamine. Socially reared controls acquired readily a selective response upon the drug lever. However, isolation reared animals acquired a selective response at a greatly retarded rate. In experiment 2b, a full d-amphetamine dose-response function was examined. Isolation rearing impaired the response to a range of doses of d-amphetamine. In experiment 2c, the infusate (1 microgram d-amphetamine per infusion) was adulterated with either SCH-23390 or sulpiride. Adulteration with either dopamine receptor antagonist enhanced the rate of response by socially reared controls. Isolation rearing impaired this response to SCH-23390, and blocked the response to sulpiride. These data are discussed in relation to the functioning of cortico limbic-striatal systems, with particular reference to the mesoaccumbens dopamine projection. PMID- 7871085 TI - Pharmacological models of memory dysfunction? A comparison of the effects of scopolamine and lorazepam on word valence ratings, priming and recall. AB - The effects of scopolamine (0.3, 0.6 mg IM) lorazepam (2 mg oral) and placebo on word valence ratings, priming and word recall were assessed in a double-blind independent group design with 36 subjects. Subjects given active drugs rated words as having more of an affective load than subjects given placebo. Priming, as assessed in a word-stem completion task, was not significantly affected by any treatment. Word recall showed some impairment following all active treatments. Performance on the stem completion task was unrelated to subjectively rated sedation but did not relate to word-valence ratings in different ways across drug treatments. Performance on the recall task was unrelated to valence ratings but did relate to the sedative effects on lorazepam. Implications are drawn out for pharmacological models of memory dysfunction. PMID- 7871086 TI - CCK-A and CCK-B selective receptor agonists and antagonists modulate olfactory recognition in male rats. AB - Modulation of learning and memory is one of the physiological roles that the neuropeptide cholecystokinin (CCK-8) may play. We have used a behavioural model of olfactory recognition among rats to test this hypothesis and to explore the relationship between CCK-A and CCK-B receptors and memory retention. Adult male rats form a transient memory of a juvenile congenere as indicated by a reduction in the duration of investigatory behaviour upon re-exposure 30 min after an initial exposure, but not when re-exposure is delayed until 120 min afterwards. In the present study, rats were treated after the first contact with various compounds; inhibition and facilitation of olfactory recognition were evaluated as the persistence in investigation 30 min and the decrease in investigation 120 min after pharmacological manipulations, respectively. Systemic injection of CCK-8, of a selective CCK-A agonist, or of non-peptide CCK-B antagonists (CI-988 and LY 262691) enhanced olfactory recognition. In contrast, the CCK-B selective agonist BC 264 and the tetrapeptide CCK-4 both disrupted it. Taken together with previous evidence of the detrimental effect of the nonpeptide. CCK-A antagonist devazepide on olfactory recognition, these results confirm and extend the hypothesis that there is a balance between CCK-A-mediated facilitative effects and CCK-B-mediated inhibitory effects on memory retention. PMID- 7871087 TI - Parallel changes in dopamine D2 receptor binding in limbic forebrain associated with chronic mild stress-induced anhedonia and its reversal by imipramine. AB - Chronic sequential exposure to a variety of mild stressors has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions, associated with abnormalities of dopaminergic neurotransmission in the nucleus accumbens. In the present study, 5 weeks of treatment with imipramine (10 mg/kg b.i.d.) reversed the decreased sucrose intake of rats exposed to chronic mild stress. Stress also caused a decrease in D2 receptor binding in the limbic forebrain (but not the striatum), which was completely reversed by imipramine. In nonstressed animals, imipramine decreased D1-receptor binding in both regions. However, in stressed animals, imipramine did not significantly alter D1-receptor binding in either area. Stress alone slightly increased D1-receptor binding, in striatum only. Scatchard analysis showed that all changes in receptor binding resulted from changes in receptor number (Bmax) rather than receptor affinity (KD). The results support the hypothesis that changes in D2-receptor function in the nucleus accumbens are responsible for chronic mild stress-induced anhedonia and its reversal by antidepressant drugs. They do not support the hypothesis that the sensitization of D2-receptors seen following chronic antidepressant treatment is caused by a down-regulation of D1 receptors. PMID- 7871088 TI - D1 and D2 dopamine receptor antagonists reverse prepulse inhibition deficits in an animal model of schizophrenia. AB - The amplitude of the acoustic startle response is decreased if the startle stimulus is preceded by a nonstartle eliciting stimulus. This sensorimotor gating phenomenon, known as prepulse inhibition, is diminished in schizophrenic individuals. In rats, the dopamine agonist apomorphine disrupts prepulse inhibition and this disruption is reversed by classical and atypical antipsychotics. Furthermore, the ability of antipsychotics to reverse the apomorphine disruption is correlated with clinical potency and D2 receptor affinity. In the present study, the role of the D1 receptor in prepulse inhibition of the acoustic startle response was studied; the effects of the D1 receptor antagonist SCH 23390 were examined and compared to the effects of the D2 receptor antagonist eticlopride. Male Sprague-Dawley rats were placed into a startle chamber and presented with auditory stimuli consisting of either 95 or 105 dB noise bursts presented alone or preceded by a 75 dB noise burst. Trials consisting of no stimulus and the 75 dB prepulse stimulus alone were also included. These six trial types (ten each) were randomly presented within a 35 min session. Rats treated with 2.0 mg/kg apomorphine (SC) demonstrated a significant disruption of prepulse inhibition compared to vehicle controls. Pretreatment with the D1 antagonist SCH 23390 (0.01, 0.05, 0.1 mg/kg SC) or the D2 antagonist eticlopride (0.01, 0.05, 0.1 mg/kg SC) attenuated the disruptive effects of apomorphine. These results indicate that selective blockade of either the D1 or D2 receptor subtype is sufficient in reversing the sensorimotor gating deficits produced by apomorphine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871089 TI - Reversal of stress-induced anhedonia by the dopamine receptor agonist, pramipexole. AB - Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of a palatable (1%) sucrose solution, and to attenuate food-induced place preference conditioning. In this study the effects of pramipexole (SND-919), a dopamine D2 agonist, were studied during 7-9 weeks of chronic treatment. Pramipexole (1.0 mg/kg per day) reversed the suppression of sucrose intake in stressed animals, increasing sucrose intakes above the levels seen in untreated nonstressed controls. Pramipexole also increased sucrose intake in nonstressed animals; these effects were accompanied by increases in water intake and tended to correlate with weight loss. Drug-treated stressed animals also lost weight, but in this case water intake was unaffected. A second group of animals received a higher dose of pramipexole (2.0 mg/kg per day). The effects of the two doses were very similar. After three weeks of treatment, these animals were switched to a lower dose of pramipexole (0.1 mg/kg per day). Increases in sucrose intake were maintained over three weeks of treatment at the lower dose, with significant recovery of body weight. Two further groups received the same doses of pramipexole (1.0 mg/kg for 6 weeks or 2.0 mg/kg for 3 weeks followed by 0.1 mg/kg thereafter), but received intermittent (twice-weekly) drug treatment. Intermittent pramipexole treatments also tended to increase sucrose intakes, but the results were less consistent from week to week. Following 6-8 weeks of pramipexole treatment, food-induced place preference conditioning was studied in all animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871090 TI - Evaluating the effects of an alpha-2 adrenoceptor antagonist on erectile function in the human male. 1. The erectile response to erotic stimuli in volunteers. AB - The effects of a new alpha-2 adrenoceptor antagonist on erectile function was assessed in 12 normal volunteers (mean age 28.7, range 20-42), using a double blind, placebo controlled design with two doses of drug and three testing sessions. The drug was administered by intravenous infusion and erectile responses to erotic fantasy and films were monitored by a Rigiscan device. Four effects of the drug were observed; (i) an increase in spontaneous erections; (ii) increased subjective ratings of sexual arousal, before presentation of erotic stimuli; (iii) increased duration of erectile response to erotic stimuli; and (iv) increases in systolic BP and HR both before and during erotic stimulation. These effects were largely restricted to the high dose of the drug. Adverse effects of the drug were minimal. PMID- 7871091 TI - Evaluating the effects of an alpha-2 adrenoceptor antagonist on erectile function in the human male. 2. The erectile response to erotic stimuli in men with erectile dysfunction, in relation to age and in comparison with normal volunteers. AB - The effect of a new alpha-2 adrenoceptor antagonist on erectile function was assessed in 24 men with probable psychogenic erectile dysfunction. The drug was given in two dosages, together with placebo, by intravenous infusion in a balanced cross over design. Once plasma levels were established, erectile, subjective and haemodynamic responses to erotic fantasy and films were measured. Subjects were divided into two age groups, "Younger" (i.e. less than 45 years) and "Older" (greater than 45 years). There was a significant though modest increase in the duration of erectile response with the high dose of the drug, but only in the younger men. There were also drug effects on haemodynamic responses confined to the younger men, who showed markedly reduced responses during placebo administration when compared with the older dysfunctional men and with young "functional" volunteers. The findings raise the possibility that in younger men with psychogenic erectile failure, there is an inhibition of general arousal responses to erotic stimuli which is partially reversed by this drug. In the older men, the different pattern of response suggests that a) there may be a decline in response to the drug with age and b) other age-related factors are playing an important part in the aetiology of their erectile failure. PMID- 7871092 TI - Alpha 2-adrenoceptor blockade, pituitary-adrenal hormones, and agonistic interactions in rats. AB - The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. Alpha 2 adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an alpha 2 adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different alpha 2 adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the alpha 2 adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed. PMID- 7871094 TI - Treatment of chronic depression with sulpiride: evidence of efficacy in placebo controlled single case studies. AB - Systematic variation of treatment (alternating active drug and placebo in four treatment periods) in individual patients is proposed to collect preliminary evidence for a therapeutic effect of sulpiride in chronic depression; the ARIMA model is applied to evaluate the intervention effects of the tentatively effective treatment in single subjects. Ten single cases of chronic depression with a diagnosis of major depression or dysthymia were selected and seven of these provided evidence for beneficial effects of sulpiride with regard to treating the symptoms of depression and anxiety. However, the drug effects were intraindividually not always replicable. The results obtained with these single cases positively support the recommendation to perform regular randomized placebo controlled trials with sulpiride in chronic depression. Simultaneously, these single case investigations reveal a lack of temporal stability of treatment response and inconsistencies of response with regard to different treatment targets in individual patients. PMID- 7871093 TI - Effects of disrupting the cholinergic system on short-term spatial memory in rats. AB - The effects of disrupting the muscarinic or nicotinic systems on short-term spatial memory were investigated using a delayed matching to position (DMTP) procedure. Rats were trained on the DMTP until stability and then divided into two groups: one group was implanted with an indwelling cannula aimed at the lateral ventricle. The cannulated group received injections of selective muscarinic antagonists (pirenzepine, M1; AFDX 116, M2; UH-AH 37, M1/M3) or hemicholinium-3 (a choline uptake inhibitor). The remaining animals were treated with conventional muscarinic antagonists (scopolamine, methyl scopolamine) or nicotinic channel blockers (mecamylamine, hexamethonium). Scopolamine, methyl scopolamine and UH-AH 37 disrupted all performance parameters in a non-specific but dose related manner. Pirenzepine disrupted accuracy in a delay, but not dose dependent manner, and exerted no other negative effects on performance. Hemicholinium-3-induced performance deficits showed some elements of effects seen following pirenzepine and scopolamine (delay dependent effects on accuracy, some negative effects on other motoric aspects of performance). AFDX 116 and hexamethonium had no significant effects on performance with respect to control. Mecamylamine reduced accuracy and increased response latencies at the highest dose tested. These data indicate that muscarinic antagonists are more effective at disrupting mnemonic performance than nicotinic blockers, and moreover, that distinct muscarinic receptors may have differential effects on cognitive performance. PMID- 7871095 TI - Brain uptake and distribution of the potential memory enhancer CL 275,838 and its main metabolites in rats: relationship between brain concentrations and in vitro potencies on neurotransmitter mechanisms. AB - The kinetics, brain uptake and distribution of CL 275,838, a potential memory enhancer, and its main metabolites (II and IV) were evaluated in rats after intraperitoneal doses of 5, 10 and 20 mg/kg. Brain maximum concentrations (Cmax) of the three compounds after pharmacologically active doses were then related to the in vitro concentrations affecting some monoaminergic and amino acid receptor sites to examine the relative importance of these neurotransmitter systems in the pharmacological actions of CL 275,838. After 10 mg/kg CL 275,838, the unchanged compound rapidly entered the brain and distributed almost uniformly in various regions inside the blood-brain barrier. Its disappearance from brain and plasma was almost parallel with a comparable elimination half-life (t 1/2) of about 2 h. Metabolite II entered the brain and equilibrated with plasma more slowly than the parent compound, achieving mean Cmax (0.2 microM) within 3 h of dosing. Metabolite IV was rapidly detected in rat brain but hardly amounted to 10% (0.1 microM) of the parent compound Cmax (1 microM). There was a linear relationship between dose and plasma and brain concentrations of the three compounds up to 20 mg/kg CL 275,838. At micromolar concentrations the parent compound had affinity for serotonin (5-HT) uptake sites, 5-HT2 and dopamine (DA2) receptors. Only at much higher concentrations than those achieved in vivo after pharmacologically active doses did it increase the binding of 3H-glutamate to NMDA (N-methyl-D aspartate) receptors. Metabolite II has a similar neurochemical profile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871096 TI - Discriminating the effects of triazolam on stimulus and response processing by means of reaction time and P300 latency. AB - The benzodiazepines slow information processing and the sites of this slowing were mapped using the Additive Factors Method in combination with the P300 component of the event-related brain potential. It was assumed that P300 largely reflects the time to evaluate a stimulus while reaction time (RT) reflects this time plus the time to select and execute a response. Twelve subjects were administered 0.25 mg triazolam in a repeated measures single-blind design. A visual 80-20% oddball task was used in which stimulus intensity and signal quality were manipulated with accuracy of responding held constant at a high level. RT and EEG data were collected simultaneously and the P300 elicited by the low probability stimuli was measured on a single trial basis. Triazolam slowed RT (172 ms, P < 0.0003) more than P300 (88 ms, P < 0.0007), but both measures exhibited a drug x stimulus intensity interaction. RT also exhibited a drug x signal quality interaction but P300 did not. These results suggest that triazolam has selective effects on perceptual processing by slowing an early pre-processing stage but not a later feature extraction stage. In addition, the drug appears to slow some aspect of response processing. This evidence is taken as support for a multiple process rather than a general sedation view of benzodiazepine effects on stages of processing. PMID- 7871097 TI - Glutamate-dopamine interactions in the ventral striatum: role in locomotor activity and responding with conditioned reinforcement. AB - Previous evidence suggests that glutamatergic limbic afferents participate in the potentiation of responding with conditioned reinforcement produced by intra accumbens d-amphetamine. The present experiments were designed to investigate glutamate-dopamine interactions in the ventral striatum in both conditioned reinforcement and locomotor activity. Glutamate receptor agonists and antagonists were infused into the nucleus accumbens both alone and in combination with 3 micrograms d-amphetamine, and the effects of these interactions on responding with conditioned reinforcement and locomotor activity were measured. The glutamate receptor agonists NMDA, AMPA and quisqualate (agonists at the NMDA, AMPA and metabotropic glutamate receptor subtypes, respectively) and the antagonists AP5 and CNQX, (antagonists at the NMDA and AMPA receptor subtypes, respectively) were used in these investigations. These compounds were used in a dose range of 0.3 to 3 nmol, except CNQX, which was used in 0.2 to 2 nmol doses. While all agonists and antagonists increased locomotor activity when administered alone, the antagonists attenuated the locomotor response to d-amphetamine. In contrast, the agonists AMPA and quisqualate enhanced d-amphetamine-induced locomotor activity, although NMDA interfered with the effects of d-amphetamine. In the conditioned reinforcement paradigm, both the agonists and the antagonists abolished amphetamine's potentiation of responding with conditioned reinforcement, suggesting that the glutamatergic transmission of information about the conditioned reinforcer could be blocked by glutamate receptor antagonists and disrupted by administration of the agonists. The dissociation between the effects of these excitatory amino acids on amphetamine-induced locomotor activity versus their effects on amphetamine's potentiation of responding with conditioned reinforcement provides insight into the nature of the reward enhancement by accumbens dopamine versus its locomotor stimulant effects. PMID- 7871099 TI - Improvements in performance without nicotine withdrawal. AB - Two tests were made of the withdrawal-relief explanation of the improvements in performance obtained with smoking. Study 1 examined the extent to which abstinence from smoking produced poorer performance in smokers in comparison with non-smokers. No evidence was obtained of differences in performance in smokers who were deprived of cigarettes for 10 h and non-smokers. Study 2 tested smokers with a standard cigarette or sham smoking after one hour and 12 h of deprivation. There was no difference in performance for the two deprivation intervals either in the sham smoking condition, or after smoking the lit cigarette. This study gave no evidence for withdrawal-relief being an explanation of the improvements in performance obtained with smoking. PMID- 7871098 TI - Preference for ethanol and diazepam in light and moderate social drinkers: a within-subjects study. AB - Preference for ethanol (versus placebo) and diazepam (versus placebo) was assessed in light and moderate social drinkers. The study was designed to investigate the relationship of habitual alcohol use to the subjective and behavioral effects of the two drugs. A secondary purpose of the study was to investigate relationships within subjects in their responses to ethanol and diazepam. Light drinkers (n = 13) who consumed one to five drinks per week and moderate drinkers (n = 14) who consumed seven or more drinks per week participated in two seven-session choice experiments, one assessing preference for 0.5 g/kg ethanol versus placebo and the other assessing preference for 20 mg diazepam versus placebo. Drugs were administered double-blind and double-dummy, and the order of participation in the two experiments was counterbalanced. Sessions were conducted during the evenings in a comfortable laboratory environment. The primary dependent measure was the number of times each subject chose the drug (i.e., ethanol or diazepam) over placebo. Subjective and objective measures of the drugs' effects were obtained using standardized self-report questionnaires and psychomotor tests. Whereas both groups preferred the ethanol over placebo (i.e., 63% and 83% ethanol choice for light and moderate drinkers, respectively), only the moderate drinkers preferred the diazepam over placebo (i.e., 40% and 73% diazepam choice for light and moderate drinkers, respectively). Subjective responses to the drugs were generally similar across the groups, although on some measures the light drinkers reported more marked drug effects. The number of times each subject chose ethanol was positively correlated with the number of times he or she chose diazepam (r = 0.57), and on subjective measures, responses to ethanol and diazepam were positively correlated. Thus, subjective and behavioral responses to diazepam and ethanol were related to habitual alcohol consumption, and most notably, moderate drinkers were more likely than light drinkers to prefer diazepam over a placebo. PMID- 7871100 TI - Up-regulation of beta 1-adrenergic receptors in rat brain after chronic citalopram and fluoxetine treatments. AB - Quantitative receptor autoradiography was used to study the effects of the selective serotonin reuptake inhibitors citalopram and fluoxetine and the tricyclic antidepressant imipramine on the regulation of beta 1-adrenergic receptors in the rat brain. Rats were treated with saline, citalopram (10 mg kg 1), fluoxetine (10 mg kg-1), or imipramine (15 mg kg-1) SC once daily for 14 days. [125I]Iodocyanopindolol binding to beta 1-adrenergic receptors was found to increase significantly in the caudate-putamen and the somatosensory areas of the frontal cortex after both citalopram and fluoxetine treatments. Imipramine treatment elicited a marked decrease in beta 1 binding in the outer laminae of the cingulate cortex, as well as in the motor and somatosensory areas of the frontal cortex. In a separate experiment, rats were treated with saline, citalopram (2.5, 10 and 20 mg kg-1) or fluoxetine (2.5, 10 and 20 mg kg-1) SC once daily for 14 days. The effects of citalopram and fluoxetine on beta 1 receptors in the somatosensory cortex and caudate-putamen were replicated. These results demonstrate that chronic administration of selective serotonin reuptake inhibitors, in contrast to imipramine, can cause a regional up-regulation of beta 1-adrenergic receptors in the rat brain. PMID- 7871101 TI - Does nicotine improve cognitive function? PMID- 7871102 TI - Dietary cholesterol, serum cholesterol and destructive behavior. PMID- 7871103 TI - Modification of rat plasma lipoproteins induced by acute immobilization stress. AB - To determine the influence of acute stress on plasma lipids and lipoproteins, 66 Wistar rats (31 males and 35 females) were immobilized for 10 hours. Previously, these animals were deprived of food for another 10 hours. Because immobilization involves forced fasting, the control group consisted of 58 rats (30 males and 28 females) that fasted for 20 hours. The immobilized animals showed gastric lesions (94% of the males and 83% of the females). Plasma lipoproteins were separated by ultracentrifugation in the following densities: less than 1.006 g/ml (very low density lipoproteins (VLDL)), 1.006 to 1.040 g/ml (low-density lipoproteins (LDL)), 1.040 to 1.063 g/ml (high-density lipoproteins fraction 1 (HDL1)), and 1.063 to 1.210 g/ml (HDL2). Measurements were adjusted according to hematocrit value. In male rats, immobilization caused a rise in total plasma cholesterol as a consequence of increases in the VLDL, LDL, and HDL1 fractions. In female rats, however, no significant variations were observed in plasma cholesterol, although there was a slight, but significant, increase in VLDL and LDL cholesterol. Immobilization caused hypertriglyceridemia in both sexes as a result of an increase in triglycerides in all classes of lipoproteins, except in HDL2 in both sexes and VLDL in males. Finally, the protein content of VLDL and LDL increased both in male and female rats; HDL2 levels decreased in female rats. These changes suggest an atherogenic character of stress caused by continuous immobilization during 10 hours. PMID- 7871104 TI - Partial sleep deprivation reduces natural killer cell activity in humans. AB - Sleep disturbance, measured by either subjective report or electroencephalographic (EEG) assessment of sleep, correlates with a reduction of natural killer (NK) cell activity in major depression. To test whether sleep loss independent of mood disturbance alters daytime values of cellular immune function, the effect of late-night partial sleep deprivation on NK cell activity was studied in 23 medically and psychiatrically healthy male volunteers. After a night of sleep deprivation between 3 and 7 AM, NK cell activity was reduced in 18 of the 23 subjects with average lytic activity reduced significantly (p < .01) to a level 72% of the mean of three separate baseline values. After a night of resumed nocturnal sleep, NK cell activity had returned to baseline levels. These data implicate sleep in the modulation of natural immunity and demonstrate that even modest disturbances of sleep produce a reduction of NK cell activity. PMID- 7871105 TI - Immunological and physiological changes associated with induced positive and negative mood. AB - Functional and phenotypic immunological parameters were examined before, at the end of, and 20 minutes after the induction of positive and negative mood states, varied for arousal level, and a neutral state. The subjects were 14 male actors who experienced each condition on a different day. Compared with a neutral condition, all mood states affected several immune parameters (e.g., natural killer cell percentage and activity and percentage of suppressor/cytotoxic T cells), regardless of the valence or arousal level of the mood induced. The only immune variable differentially sensitive to positive and negative mood states was the proliferative response to the mitogen phytohemagglutinin; the response increased after positive moods and decreased after negative moods. Analysis of covariance for repeated measures indicated that heart rate, alone or in combination with physical activity and cortisol levels, had an impact on mood effects for most of the immune parameters investigated. PMID- 7871106 TI - Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome. AB - The psychobehavioral responses and cellular immune function were investigated in healthy people (control, N = 21), adult people with chronic fatigue (fatigue-non CFS group, N = 24), and patients with chronic fatigue syndrome (CFS, N = 10). Based on psychobehavioral responses, the fatigue-non-CFS group had low general activity levels (p < .05) and slightly depressive tendencies (p < .01) compared with the control. They had many life event stresses (p < .05) and sleep disturbances (p < .01), and they could not cope appropriately with stresses. The fatigue-non-CFS group also showed significantly lower natural killer (NK) cell activity (p < .01) and decreased numbers of CD16+ and CD56+ cells (p < .05). Compared with the fatigue-non-CFS group, patients with CFS had higher degrees of physical fatigue (p < .01) and more life event stresses (p < .05). They had lower general activity levels and social introversion. They were also in a depressive state. NK cell activity and the numbers of CD16+ and CD56+ cells were significantly reduced in patients with CFS (p < .01). These findings suggest that adult people with chronic fatigue may be in an intermediate state between the healthy control and patients with CFS in terms of psychobehavioral responses and low NK cell activity. We observed three cases in such an intermediate state in whom CFS subsequently developed. PMID- 7871107 TI - Hostility and the progression of carotid atherosclerosis. AB - We studied prospectively the association of hostility and anger suppression by the use of ultrasonographically assessed 2-year progression of carotid atherosclerosis (PCA) in a sample of 119 middle-aged men from eastern Finland. Based on measures of cynical distrust, impatience-irritability, anger-in, and anger-control, four variants of hostility-by-anger suppression model were tested with multiple regression analysis. In addition to the previously established risk factors (i.e., serum low-density lipoprotein cholesterol concentration, smoking, and old age), cynical distrust and anger-control significantly predicted PCA. There was about a two-fold accelerated PCA in the group with high cynical distrust and high anger-control even after we controlled for the established biological risk factors and possible confounding background variables. The impact of the independent variables on PCA seemed to be additive rather than synergistic. These results, based on a relatively small, but nonselected population sample, extend previous results of angiographic studies. PMID- 7871108 TI - Psychological effects of presymptomatic DNA testing for Huntington's disease in the Dutch program. AB - This study assessed the 6-month follow-up effects of presymptomatic DNA testing for Huntington's disease (HD) in 73 individuals at 50% prior risk who were identified either as carriers of the HD gene (N = 29) or as noncarriers (N = 44). The subject's knowledge of being a gene carrier was expected to induce intrusive emotions, denial-avoidance behavior, and pessimistic expectancies of the future and adjustment problems. The Impact of Event Scale, the Beck Hopelessness Scale, and the General Health Questionnaire were used as standard measures of psychological distress. At the disclosure of the test results, carriers had a strong increase in pessimistic expectations but showed a decline to baseline levels 6 months later. Noncarriers reported a steep decline in hopelessness compared with their pretest conditions but had increased scores after 6 months. Six months after the disclosure of the test results, both gene carriers and noncarriers reported a significant decrease in unwanted intrusive thoughts about HD. Carriers showed a slight increase in denial-avoidance behavior, whereas noncarriers showed a clear decrease. Our observations might indicate that tested individuals found relief from the prior psychological distress and that they were able to acknowledge the impact of the test result on their future. An unresolved question is how the foreknowledge will affect carriers as they approach the impending onset of the disease. Longer observation periods (> 6 months after disclosure) are required to study changes of the impact of DNA test results over time. PMID- 7871109 TI - Overreactivity of the psyche or the soma? Interindividual associations between psychosomatic symptoms, anxiety, heart rate, and end-tidal partial carbon dioxide pressure. AB - Current research has all but refuted previous suggestions about the role of hyperventilation as a proximal, common cause of psychosomatic symptoms. As an alternative, it has been proposed that the experience of psychosomatic symptoms is primarily associated with psychological mechanisms, i.e., with enhanced tendencies of distressed individuals to focus their attention on bodily sensations and to evaluate these in a catastrophic manner. Although this hypothesis has received considerable empirical support, physiological influences on symptom reporting have not, as yet, been fully explored. In this study, contributions of psychological and physiological factors were studied among a group of 83 normal healthy male subjects by an assessment of the interindividual relationships between symptom experience in daily life, situational and dispositional anxiety, baseline end-tidal partial carbon dioxide pressure (PCO2), and heart rate. Trait anxiety and end-tidal PCO2 each contributed separately to the prediction of the psychosomatic symptom score. Trait anxiety explained nearly one third of the symptom variance, and an additional 4% was explained by PCO2. Psychological symptoms were more strongly associated with anxiety and somatic symptoms, more strongly with PCO2. Heart rate only tended to be correlated with symptom reporting. Analysis of covariance among subgroups of extreme-symptom reporters supported the correlational findings by demonstrating that the association between hyperventilation and symptom reporting remained intact when psychological influences were factored out. The findings suggest that reports of psychosomatic symptoms represent two distinct components: one that is primarily psychological (and is unrelated to physiological factors) and a second that reflects objective variance in physiological functioning. The influence of the first component is probably greater than that of the second. PMID- 7871110 TI - Modeling and reinforcement of the sick role during childhood predicts adult illness behavior. AB - Previous studies suggest that the ways in which parents respond to children's health complaints (reinforcement) and the ways in which they cope with their own illnesses (modeling) influence the frequency of symptoms, disability days, and health care visits made by these children when they grow up. However, previous studies have not controlled for the mediating influence of stress, neuroticism, and physical examination findings. This study investigated the influence of childhood social learning on adult illness behavior in 383 women aged 20 to 40 years. Illness behavior was measured prospectively for 12 months by the frequency of symptoms, disability days, and physician visits for menstrual, bowel, and cold (upper respiratory) symptoms. Childhood reinforcement and modeling was measured retrospectively by validated questionnaires. Other independent variables were stress, neuroticism, and selected demographic variables. Multiple regression analysis was used to assess the relative contribution of each independent variable to each category of illness behavior. The principal findings were as follows. First, childhood reinforcement of menstrual illness behavior significantly predicted adult menstrual symptoms and disability days, and childhood reinforcement of cold illness behavior significantly predicted adult cold symptoms and disability days. These effects were independent of stress and neuroticism. Second, childhood reinforcement scales were useful to predict which functional disorders (dysmenorrhea or irritable bowel syndrome) these subjects had even after we controlled for stress and neuroticism. PMID- 7871111 TI - Somatic symptoms in Turkish and German depressed patients. AB - We determined the pattern and severity of symptoms in Turkish and German depressed inpatients. Psychopathological and somatic symptoms were documented on standardized rating scales of the Association for Methodology and Documentation in Psychiatry (AMDP) System. Of a total sample of 6000 inpatients admitted to the Psychiatric Department of the Free University of Berlin from 1981 to 1989, 28 Turkish inpatients with diagnoses of depression, according to the International Classification of Diseases, ninth revision, were compared with a randomly selected group of matched German depressed inpatients. Turkish patients scored higher only on the Vegetative-somatic syndrome scale but did not differ on the Depressive or Apathetic syndrome scale of the AMDP System. PMID- 7871112 TI - Conscious and unconscious coping with loss. AB - Sixty-seven persons were identified 1 to 2 months after the death or life threatening illness of their spouse and followed for 25 months. Intake measures included a) a revised Ways of Coping Scale, a structured assessment of ego defenses, sociodemographic information, and other baseline variables. Fifty-six completed follow-up. Outcome measures included deaths, hospitalization, self rated health, depressive symptoms, symptoms of anxiety, and separation distress. In our analyses, bereavement was used as a covariate and found to be unrelated to outcome. Low self-ratings on coping by making a change and problem-focused planning predicted higher scores on separation distress at 13 months (p < or = .05). Participants who used less problem-focused planning were at risk for higher depression scores 13 months after the stressful event (p < or = .05). Low ego defensive work and high neurotic ego-defensive ratings predicted high depression scores at 13 months (p < or = .05). At 25 months, coping by self-blame was inversely related to scores on separation distress (p < or = .05). Coping variables predicted neither scores on anxiety symptom scales nor the outcomes of hospitalization or death over the 25-month study period. These observations counter some prevailing clinical assumptions about coping with a loss and emphasize the value of empirical studies of coping as a mediator of outcome during the stress of a loss. PMID- 7871113 TI - Briquet's syndrome (hysteria) is both a somatoform and a "psychoform" illness: a Minnesota Multiphasic Personality Inventory study. AB - We describe the results of a follow-up study on patients with hysteria using the Minnesota Multiphasic Personality Inventory (MMPI) to evaluate the multiple complaints of these patients. MMPIs were obtained from 29 women with primary affective disorder and 37 women with Briquet's syndrome as part of a follow-up study of the St. Louis clinic 500. Patients with Briquet's syndrome were significantly less consistent and logical in answering MMPIs and were more likely to emphasize personal psychopathological conditions. They reported many more symptoms in many more problem areas than did women with primary affective disorder. Patients with Briquet's syndrome reported significantly more somatic symptoms and psychological/interpersonal problems than did the depressed group. It was suggested that such patients mimic multiple psychiatric and somatic disorders. PMID- 7871115 TI - Inferring vagal tone from heart rate variability. PMID- 7871114 TI - Validation of two anxiety scales in a university primary care clinic. AB - Psychometric scales for the assessment of anxiety disorders have not been validated in primary care settings. We undertook a study to validate two brief, self-administered anxiety scales, Sheehan's Patient-Rated Anxiety Scale and Beck's Cognition Checklist, in a university primary care clinic. The two scales were compared with a diagnostic standard, the Structured Clinical Interview for the revised third edition of the Diagnostic and Statistical Manual (SCID). Of 87 randomly selected patients, 25 had an anxiety disorder by the SCID. Anxious patients scored statistically higher on both scales than nonanxious persons on both the Beck and Sheehan scales. Based on receiver operating characteristics curve analysis, we found that these two scales correctly classified 72% to 77% of anxious patients. Of the two scales, the Sheehan scale performed better, with a specificity of 94% and positive predictive value of 75%. Our results suggest that these instruments may be useful in the assessment of the anxiety disorders in medical populations. PMID- 7871116 TI - Brain changes and negative symptoms in schizophrenia. AB - Negative symptoms (and cognitive impairments) in schizophrenia are a correlate of early onset and poor outcome. It is plausible that they are related to an arrest of brain development, for which there is now considerable evidence, but the precise relationship is elusive. In one post-mortem study negative symptoms were related to a reduction in brain length and in an MRI study to an asymmetry of sulcal CSF. It is proposed that the phenomena of psychosis (including negative symptoms) can be understood as part of the diversity of human personality structure generated by a process of sexual selection acting on a sexual dimorphism for cerebral asymmetry. PMID- 7871117 TI - Psychopathology of Schizophrenia: initial validation of a 5-factor model. AB - Schizophrenic psychopathology is heterogeneous and multidimensional. One of the more fruitful strategies to investigate more homogenous domains of psychopathology has been the positive-negative syndrome approach. However, this approach is unable to address a number of important issues. Most schizophrenics present a mixed syndrome; the criteria for what constitutes a positive and negative syndrome are variable; distinguishing primary from secondary negative symptoms can be difficult. In order to address some of these problems, we propose the introduction of a 5-syndrome model based on a reanalysis of factor-analytic procedures used on 240 schizophrenics assessed with the Positive and Negative Syndrome Scale: A negative, positive, excitement, cognitive and depression/anxiety factor. This 5-factor solution is supported by 4 independent and comparable factor analyses. Data on internal consistency of the 5 factors and on initial validation using demographic and clinical variables are presented. PMID- 7871118 TI - Validity of the negative/positive dichotomy of schizophrenic disorders under long term conditions. AB - Based on the phenomenological distinction of positive and negative symptoms, some authors discuss the existence of two subtypes of schizophrenia (positive vs. negative schizophrenia). Investigating the long-term course of 100 schizophrenic patients (on average 23 years after onset) it was found that only 24% of the patients had a stable monomorphous course (only once type of episode). The results of the presented longitudinal study do not support the assumption of 'purely positive' or 'purely negative' schizophrenic disorders. The relevance of positive and negative onset of illness for the long-term course and outcome is discussed with reference to the literature. PMID- 7871119 TI - Structural and functional correlates of subsyndromes in chronic schizophrenia. AB - Recent psychopathological studies consistently identified a delusional, a negative, and a disorganized subsyndrome in chronic schizophrenia. The aim of our studies was to investigate the subsyndromes with respect to their underlying cerebral changes using computed tomography (CT) and positron emission tomography (PET). In a CT study 50 DSM III schizophrenics were subgrouped according to four factors identified by a factor analysis of BPRS ratings. This procedure identified three chronic clusters (delusional ideation, negative symptoms, and disorganization) and one cluster with a remitting course of the disorder. Both the negative and the delusional subsyndrome were associated with a widening of the frontal interhemispheric fissure. Disorganization was associated with neurological soft signs, an increased ventricle brain ratio, and width of the 3rd ventricle. The same subgrouping was applied in a 18F-deoxyglucose PET study of 79 neuroleptic free DSM III schizophrenic patients and 47 healthy controls. The delusional subsyndrome was associated with a decreased hippocampal function, while the negative subsyndrome showed a prominent hypofrontality and left temporal cortex changes. Both the delusional and the negative subsyndrome were associated with a decreased activity in the medial frontal gyrus in comparison to the other schizophrenic patients and the healthy controls. The disorganized subsyndrome was characterized by an overactivity in the parietal cortex and motor strip and a decreased activity in the corpus callosum. These findings support the differentiation of three subsyndromes in chronic schizophrenia. The subsyndromes seem to be characterized by deviant patterns of cerebral alterations, rather than deficits in a single location. PMID- 7871120 TI - The core of negative symptoms in schizophrenia: affect or cognitive deficiency? AB - The association of negative symptoms on one hand and cognitive failures and language and thought disturbances on the other hand was examined in 25 schizophrenics and 22 neurotics over a 2-month period of intensive therapy. Psychopathological negative symptoms were more pronounced in schizophrenics than in neurotics at the first assessment before intensive therapy. However, cognitive and language performance showed no difference between the groups in both cross sectional comparisons before and after treatment. Thus, our hypothesis that cognitive deficiencies are the core of negative symptoms could not be confirmed. It is discussed that young schizophrenics at an early stage of the illness may imply more affective components in the psychopathology of their negative syndrome than chronic schizophrenics with more pronounced cognitive deficits. PMID- 7871121 TI - New conceptual aspects of negative symptoms. PMID- 7871122 TI - The deficit syndrome in schizophrenic and nonschizophrenic patients: preliminary studies. AB - One hundred and eighty-seven patients suffering from DSM-III-R schizophrenia, schizoaffective, schizophreniform (psychotic group), unipolar, bipolar and other disorders were interviewed 5 years after discharge. Deficiencies were assessed by means of the Schedule for Deficit Syndrome (SDS) and the Scale for Assessment of Negative Symptoms (SANS). Binocular thresholds for discomfort to high luminances (TDHL) were assessed in 17 patients with a deficit syndrome. Results suggest that patients with psychotic disorders are in a high-risk group for deficit syndrome. Nevertheless, 9-28% and 9-30% of the 'nonpsychotic' group according to the SANS and the SDS, respectively, showed primary enduring negative symptoms. A positive correlation between the SANS total score and TDHL (r = 0.81) was found. These results suggest the nonspecificity of primary enduring negative syndromes. Furthermore preliminary data indicate a possible link between light sensitivity and the deficit syndrome, independently of diagnoses. PMID- 7871123 TI - Correlational studies of the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms: an overview and update. AB - The interrelationships between the various symptoms of schizophrenia may be explored by examining their intercorrelations. Five different factor analytic studies, which examine these interrelationships, are summarized. Three major factors emerge consistently: psychotic, disorganized, and negative. These three factors appear to represent three dimensions of the psychopathology of schizophrenia. PMID- 7871124 TI - [Group work with relatives of Alzheimer patients--a systemic approach]. AB - Dementia does not only infringe the patient's but also his caregivers' lives. The social system surrounding the patient is facing a heavy burden. The care is negatively affected by two components: lack of support from outside and problems within the relationship of patient and caregiver. In a support group for caregivers of Alzheimer patients we therefore adapted a combined approach of psycho-education and system therapy. We centered on the adverse patterns of behavior between patient and caregiver and the broadening of the support system. Techniques from systemic family therapy were used. Two cases illustrate the possibilities of this new approach to group therapy with caregivers of Alzheimer patients. PMID- 7871125 TI - [Family secrets exemplified by heterologous insemination]. AB - Potential consequences of intrafamilial concealment are discussed in the context of coping with the stigmatizing diagnosis of male infertility and its treatment by artificial insemination by donor. First results of a longitudinal study are presented. A 5-year follow-up was obtained from 40 out of 57 couples initially interviewed. 34 of the couples had kept donor insemination secret even towards their families. 10 of them considered themselves oppressed by the secrecy, especially at the time of insemination. Only two out of 26 successful couples intended to reveal details of conception to the child. These findings suggest that information of the children can follow different strategies. Children should be acquainted with details of their conception if friends or relatives of the parents are informed, in order to reduce the risk of the traumatic event of information by others. In all other cases the decision to inform children or not is to be left in the hands of the parents. Even though maximum candidness is considered desirable today, the "cathartic" revelation of family secrets can be as destructive as their conservation. PMID- 7871126 TI - [Static to sequential plan analysis]. AB - The method of Plan Analysis helps for a better understanding of the interactional engagement of the client within the client-therapist relationship. In spite of this interactional conceptualization of the method, plan analysis produces only a statical diagnosis of interpersonal intentions and plans. In order to realize a dynamical analysis of the client-therapist relationship, the method has to be modified. The steps of this modification will be explained. The result is an idiographic, discovery oriented strategy, called "Sequential Plan Analysis" (SPA), which can be used to do single case analysis of psychotherapy processes. SPA produces sequential patterns of interactional plans (nominal data) as well as quantitative time series. PMID- 7871127 TI - [Compulsive symptoms in anorexia and bulimia nervosa]. AB - The present study reports findings concerning the prevalence of obsessive compulsive symptoms in eating disorders. Ninety-three women meeting DSM-III-R criteria for anorexia nervosa (AN) or bulimia nervosa (BN) were investigated using the Hamburg Obsession Compulsion Inventory HZI-K (Klepsch et al. 1993). Forty-six patients (49.5%) met the criteria for obsessive-compulsive disorder (OCD). This subgroup showed significant pathologically elevated scores on several scales of the Eating Disorder Inventory (Garner et al. 1983), and two different personality questionnaires (Freiburger Personlichkeitsinventar, Fahrenberg et al. 1984; Giessen-Tests, Beckmann et al. 1983). The results demonstrate a high rate of OCD in AN and BN. The relationship between eating disorders and OCD and the question of clinical relevance is discussed. PMID- 7871128 TI - The environmental somatization syndrome. AB - Patients with environmental somatization syndrome (ESS) believe that their symptoms are caused by exposure to tangible components of the external environment or by ergonomic stress at work. ESS is distinguishable by mental contagiousness and by the patients' focus on the external environment as cause of the illness. The presentation is often polysymptomatic, and epidemic outbreaks may appear. The patients usually refuse alternative explanations of their symptoms and discredit and reject any suggestion of a psychogenic etiology. It is important to distinguish between hygienic problems and ESS problems, particularly when poor and inadequate hygienic factors are present simultaneously with an ESS epidemic. PMID- 7871129 TI - HIV public policy and psychiatry. An examination of ethical issues and professional guidelines. AB - The authors examine the interfaces among public policy, legal issues, ethical issues, and physician responsibility for the human immunodeficiency virus (HIV) infected psychiatric patient within the realms of civil liberties and public health. Current professional guidelines on caring for HIV-infected psychiatric patients are discussed, including discussion of psychotherapy and the potential for behavioral change. The impact of the Tarasoff decision on confidentiality is reviewed, including discussion of whether a precedent was set mandating that a psychiatrist warn identifiable third persons at risk of becoming infected by his or her patient. The management of HIV-infected psychiatric inpatients who continue to put other patients at risk and the impact of HIV carriers on ward milieu are also addressed, as are difficulties encountered with the chronically mentally ill. PMID- 7871130 TI - Psychiatric aspects of the eosinophilia-myalgia syndrome. AB - The eosinophilia-myalgia syndrome (EMS) is a rare systemic disease caused by presumably contaminated L-tryptophan. Thirteen outpatients with EMS were found to have a high degree of depression, anxiety, and difficulty adjusting to illness. Pre-EMS history of major depression but not EMS severity predicted poor adjustment to illness. PMID- 7871131 TI - The relationship between mood, somatization, and alexithymia in premenstrual syndrome. AB - To examine the relationship between mood, somatization, and alexithymia in premenstrual syndrome (PMS), 66 women with a prospectively confirmed diagnosis of PMS were compared with a group of 49 non-PMS control women on a battery of self administered tests measuring depression, anxiety, somatization, and alexithymia. Based on their scores on the Beck Depression Inventory, the PMS patients were subdivided into a high-depression and low-depression group and compared with the non-PMS control group on all test measures. Significantly greater somatization and alexithymia were reported in the high-depression PMS group, and no differences were found on any of the test measures between the low-depression PMS and non-PMS control groups. PMID- 7871132 TI - Psychiatric consultation for competency to refuse medical treatment. A retrospective study of patient characteristics and outcome. AB - Forty-one psychiatric consultations on medical-surgical inpatients for competency to refuse medical treatment were studied retrospectively. The competent (n = 16) and incompetent (n = 25) patients were compared in terms of demographic data, diagnoses, clinical variables, details about treatment refusal, and outcome following competency assessment. The incompetent patients tended to be men, the focus of more urgent requests, and to have refused operations. The incompetent patients tended to have organic brain syndromes; the competent patients had personality disorders, adjustment disorders, or no psychiatric diagnosis. Ultimate acceptance of treatment initially refused was common in both groups; differential psychiatric interventions were recommended. The process of psychiatric consultation appeared to facilitate acceptance of treatment initially refused. PMID- 7871133 TI - Factors associated with antidepressant choice. AB - Previous studies have suggested that nonpsychiatrists tend to prescribe antidepressants (ADs) with the most side effects (SEs), whereas psychiatrists are more likely to prescribe more ADs with fewer SEs. The authors used a questionnaire to examine the antidepressant prescribing pattern, conditions for which ADs were prescribed, and SEs of concern to physicians. Of those surveyed, the psychiatrists reported prescribing significantly more nortriptyline and desipramine, whereas the nonpsychiatrists prescribed more amitriptyline. The nonpsychiatrists were more likely to prescribe ADs for pain, and they were significantly less concerned with orthostatic hypotension. Possible lower dosing and level of concern about orthostatic hypotension may be related. Further study is proposed to assess other factors that might influence AD choice. PMID- 7871134 TI - Depression in the medically ill. Critical issues in diagnostic assessment. AB - Diagnosing depression in the medically ill is a difficult diagnostic task that will not be clarified appreciably by DSM-IV. The author reviews diagnostic validity as it relates to depressive disorders in the medically ill. Suggested guidelines for using the DSM-IV to diagnose depressive disorders in the medically ill also are reviewed. PMID- 7871135 TI - Munchausen syndrome presenting as recurrent multiple trauma. PMID- 7871136 TI - Factitious hypoglycemia. An 11-year follow-up. PMID- 7871137 TI - High-dose intravenous haloperidol for agitated delirium following lung transplantation. PMID- 7871138 TI - Delirium and Lyme disease. PMID- 7871139 TI - H2 blocker delirium. PMID- 7871140 TI - Sodium nitroprusside-induced delirium. PMID- 7871141 TI - Values and ideals, isms and ologies: making contact across a desert of differences. AB - The issue of communication and dialogue between academic and service public health professionals is explored. It is noted that each individual operates within his/her own personal attitudes, values and beliefs framework which has the potential to produce serious obstacles to effective communication if not taken into account and managed. The preconceptions of academic public health professionals about their service counterparts and vice versa are identified and discussed. A workshop held at the Nuffield Institute for Health, Leeds, in June 1993 is used as an example of what can happen when these barriers to communication are identified and handled sensitively. PMID- 7871142 TI - Post-defecation handwashing in Bangladesh: practice and efficiency perspectives. AB - Inadequate handwashing after defecation and anal cleaning practices in the Indian subcontinent is an important source of faeco-oral transmission of enteric diseases. To better understand the process as traditionally practised, 90 women in semi-rural Bangladesh were observed washing hands after defecation. Several components of handwashing practices were identified: the cleaning agent, using left or both hands; frequency of rubbing hands, type and amount of water used to wash, and the drying of hands on the wearer's clothes. A subsequent experiment was conducted to assess the effect of currently practised handwashing and drying according to standardised procedure on faecal coliform count of hands. As a rubbing agent, soil was commonly used (40%); soap was used by 19% and was reported unaffordable by about 81% of the non-users. Good handwashing behaviour was positively associated with better social and economic indicators including education of the women observed. Both hands were unacceptably contaminated after traditional handwashing (the geometric mean count of left was 1,995 and right hand was 1,318 faecal coliform units/hand). After standardising the observed components of handwashing procedures the use of any rubbing agent, i.e. soil, ash or soap, produced similar acceptable cleaning. Use of a rubbing agent (e.g. soil, ash or soap), more rubbing (i.e. six times), rinsing with safer water (e.g. 2 litres of tubewell water) and drying with a clean cloth or in the air produced acceptable bacteriological results. Components of traditional handwashing practices were defined through careful observation, and experiments on handwashing with standardised components showed that efficient and affordable options for handwashing can be developed; this knowledge should be helpful in disease control programmes. PMID- 7871143 TI - School health nurse interventions to increase immunisation uptake in school entrants. AB - In New South Wales, health screening of school entrants provides the only mechanism for routine monitoring of immunisation uptake in children. School health nurses are in the best position to improve the compliance with immunisation at this age. We compared two interventions to be used by the nurses to increase immunisation uptake in school entrants who reported missing either the measles-mumps vaccine and/or the pre-school diphtheria-tetanus toxoid and oral polio vaccine boosters. Parents in the passive intervention group were sent a letter and leaflet encouraging immunisation; the active intervention group received a telephone reminder from the nurse in addition to the written materials. Both groups were followed up at a later date to assess final immunisation outcome. Of 817 children screened, 88.2% had been immunised against measles and 73.6% had received the booster; 239 children were randomised to the two interventions. Excluding children lost to follow up and those fully immunised at the start of the study, 20 (37%) of 54 were immunised following the passive intervention, and 35 (71%) out of 49 following the active intervention (P = 0.001). Receipt of the letter and leaflet was associated with an increased uptake of booster vaccination (P = 0.036). The active intervention required 14.7 telephone calls and 1.6 uses of the interpreter service per completed immunisation. The passive intervention resulted in worthwhile increases in immunisation rate with minimum cost. A greater improvement in immunisation outcome was achieved by the active intervention, but its use was labour intensive and may only be warranted if high immunisation rates in this age-group are given priority. PMID- 7871144 TI - Survey of health promotion organisational arrangements and levels of service for health promotion. AB - This study was promoted by the Executive Committee of the Association of Directors of Public Health when faced with the need to examine the organisation of and quantify health promotion arrangements in the Health Districts of England and Wales, resulting from the concerns of many of the members of the Association. These concerns were based on the views that health promotion is a key purchasing function of the District Health Authorities and must be appropriately and effectively structured and adequately resourced if the requirements of The Health of The Nation are to be fulfilled. There are many aspects to health promotion work and the delivery of health promotion services which will need addressing in the new commissioning environment of the NHS. A need was recognised for up-to date data about health promotion services to inform a necessary debate about future arrangements, since it appeared that organisational change was being driven by influences unconnected with the possibly most appropriate structure of health promotion departments and which relate to a contemporary view of health promotion. Reducing the size and cutting the cost of commissioning authorities was perceived as one of the most important influences. A postal questionnaire survey to all Health District and Regional Health Authorities in England and Wales was conducted covering questions about the present organisational arrangements and levels of service, and soliciting the opinions of those canvassed. A total of 185 District and Regional Health Authorities, effectively reduced to 171 because of mergers, was sent questionnaires, of which 141 were completed and returned, giving a response rate of 82.5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871145 TI - Promoting the public health benefits of cycling. AB - The potential health gain from increased levels of cycling in Britain is large. This paper reviews current levels of bicycle ownership and use, and the factors which influence whether or not people choose to cycle in Britain. Cycle ownership is strongly associated with affluence and children. Males cycle more than females. Boys aged 11-15 years cycle the greatest number of miles per person per week, followed by men aged 16-59 years. Cycling to work is weakly associated with affluence. Modelling cycling to work patterns suggests that hilliness, traffic danger, rainfall and longer trip lengths are important deterrents to cycling. Cyclists identify cheapness, health, convenience and enjoyment as reasons for cycling. Non-cyclists identify danger, 'unpleasantness' (e.g. traffic fumes, weather), bike security and cycling not appealing as reasons for not cycling. Part of the lack of appeal of cycling reflects negative social attitudes towards cycling. Cycling has tended to be seen as a childhood activity and incompatible with an attractive and sophisticated image. Departments of Public Health Medicine and Health Promotion, in collaboration with other sectors, have an important role to play in promoting increased levels of cycling. PMID- 7871146 TI - Smoking habits of secondary school boys in rural Riyadh. AB - OBJECTIVE: To estimate the prevalence of smoking among Saudi rural secondary school students and to explore their attitudes towards smoking. DESIGN: A cross sectional study was conducted during May and June 1993, using a modified and translated version of the World Health Organization (WHO) standard questionnaire for the survey of smoking. Six rural male secondary schools near Riyadh were randomly selected, and 358 students representing half of the classes were included. RESULTS: Current smokers represented 17% of the students. The most common reasons for smoking were desire (32%), idleness (28%), imitation (22%) and enjoyment (20%). The majority knew about and understood the hazards of smoking. Around half of the smokers had started the habit before the age of 15. The media were the primary source of knowledge about smoking hazards for 66% of students; doctors (45%) and educators (30%) had a less significant role. Religion was the most important reason for not smoking among non-smokers. Financial reasons were less important (11%), probably reflecting the relatively cheap price of cigarettes. CONCLUSION: The size of the smoking problem is big enough to be considered a warning of an impending epidemic. Schools should have a greater role in health education. The government should adopt a policy of regular increases in cigarette taxes to cover part of the cost of treating smoking-related diseases. PMID- 7871147 TI - Risk factors for recurrent falls in the elderly in long-term institutional care. AB - All the persons aged 70 years or older and living in long-term institutional care in five rural northern Finnish municipalities (N = 145) were followed up for two years, and all their fall incidents were recorded through diary reporting by the nursing staff and by examining the medical records in hospitals, health centres and nursing homes. The study population was examined halfway through the follow up period by two nurses, a physiotherapist and a physician. Of the 93 ambulatory subjects, 57% of the men and 56% of the women experienced at least two falls in six months (recurrent falls): 10% of the recurrent falls resulted in a major soft tissue injury and 5% in a fracture. Logistic regression analyses showed the independent risk factors for recurrent falls to be slow walking speed, a change in living conditions during the previous two years, reduced quadriceps strength and existence of an ophthalmic disease. Many of the risk factors are potentially remediable, and they should be minimized by optimizing the care and by improving or maintaining the functional abilities of the elderly. PMID- 7871148 TI - Using mortality data to describe geographic variations in health status at sub district level. AB - OBJECTIVE: To describe sub-district variations in health status, using mortality data that are processed locally. DESIGN: A descriptive study of routinely collected death registration data, using multicause coding. SETTING: The London Borough of Croydon, with a population of 319,200 divided into 27 electoral wards. SUBJECTS: Deaths of Croydon residents, registered with the Registrar of Births and Deaths, which occurred between January 1990 and December 1992 inclusive. MAIN OUTCOME MEASURES: Variations in life expectancy, all-cause standardised mortality ratios (SMRs), and disease-specific mortality ratios between selected wards. Deaths in nursing homes were excluded to avoid bias. RESULTS: Data from 8,930 death registrations, of which 852 occurred in nursing homes, were analysed by electoral ward. The range for all-cause SMRs, including nursing home deaths, was 153 (139-168) to 66 (58-75). When nursing home deaths were excluded, the SMRs for two wards that were significantly higher than the Croydon average fell into the average range. The range, excluding nursing home deaths, was 133 (113-153) to 71 (62-80). Life expectancy at birth varied from 79.8 years to 74.4 years, and life expectancy at age 65 by three years between wards at the two ends of the spectrum. The geographic distribution of ischaemic heart disease and diabetes showed significant differences. CONCLUSIONS: We contend that death registration data are a useful tool for describing sub-district variations in health status. Deaths of nursing home residents are a source of bias and should be excluded from the analysis. Multicause coding allows a more accurate description of geographic variations in specific diseases, such as ischaemic heart disease and diabetes. PMID- 7871149 TI - Plague: past and future implications for India. PMID- 7871150 TI - Modulation of radiation-induced apoptosis and G2/M block in murine T-lymphoma cells. AB - Radiation-induced apoptosis in lymphocyte-derived cell lines is characterized by endonucleolytic cleavage of cellular DNA within hours after radiation exposure. We have studied this phenomenon qualitatively (DNA gel electrophoresis) and quantitatively (diphenylamine reagent assay) in murine EL4 T-lymphoma cells exposed to 137Cs gamma irradiation. Fragmentation was discernible within 18-24 h after exposure. It increased with time and dose and reached a plateau after 8 Gy of gamma radiation. We studied the effect of several pharmacological agents on the radiation-induced G2/M block and DNA fragmentation. The agents which reduced the radiation-induced G2/M-phase arrest (caffeine, theobromine, theophylline and 2-aminopurine) enhanced the degree of DNA fragmentation at 24 h. In contrast, the agents which sustained the radiation-induced G2/M-phase arrest (TPA, DBcAMP, IBMX and 3-aminobenzamide) inhibited the DNA fragmentation at 24 h. These studies on EL4 lymphoma cells are consistent with the hypothesis that cells with radiation induced genetic damage are eliminated by apoptosis subsequent to a G2/M block. Furthermore, it may be possible to modulate the process of radiation-induced apoptosis in lymphoma cells with pharmacological agents that modify the radiation induced G2/M block, and to use this effect in the treatment of patients with malignant disease. PMID- 7871151 TI - Ultraviolet (193, 216 and 254 nm) photoinactivation of Escherichia coli strains with different repair deficiencies. AB - Escherichia coli K12 bacteria strains AB1157 (repair-deficient wild-type, uvrA+ recA+), AB1886 (urvA-), AB2463 (recA-) and AB2480 (urvA- recA-) were exposed to 254 nm germicidal UV and 216 or 193 nm laser radiation. The mean lethal incident dose (D37) for AB1157 does not change significantly with wavelength, whereas it increases for the other strains on going from lambda irr = 254 to 193 nm, e.g. eightfold for AB2480. Quantum yields for inactivation, due to light absorbed by the chromosomal DNA, have been estimated from the D37 values. The large differences in D37 between uvrA+ and uvrA- strains indicate a significant contribution of pyrimidine dimers and (6-4) photoproducts to photodamage of DNA in the cells. The formation of dimers even with lambda irr = 193 nm is supported by the result that the photoreactivable sector is larger than 63%. Inactivation of E. coli upon irradiation at 193 and 216 nm is therefore due to damage to intracellular DNA rather than to membrane or protein damage as is the case for mammalian cells. The ratio of the lethal doses for AB1157 vs AB2480 is approximately 900 with lambda irr = 254 nm, but only 160 with lambda irr = 193 nm. We propose that this is due to the better repair of photodimers and (6-4) photoproducts than of damage induced by photoionization via upper excited states. Irradiation at 193 nm inactivates AB1157 mainly by damage due to photoionization and AB2480 by damage due to photodimers in the chromosomal DNA. PMID- 7871152 TI - Chinese hamster V79 cells harbor potentially lethal damage which is neither fixed nor repaired for long times after attaining maximal survival under growth conditions. AB - The kinetics of the repair and fixation of potentially lethal damage (PLD) was studied in log-phase Chinese hamster V79 cells. The postirradiation (10 Gy) survival of cells treated with hypertonic saline increased when these cells were incubated further in conditioned medium but not in growth medium, indicating that damage which is neither fixed by hypertonic saline nor amenable to repair in growth medium is nonetheless repaired in conditioned medium. Recovery of X irradiated cells incubated in growth medium or in conditioned medium was maximal by about 70 min and was two times higher in conditioned medium than in growth medium. Cells incubated in growth medium for 70-120 min postirradiation continued to repair damage when subsequently shifted to conditioned medium and attained the same survival as that of cells in conditioned medium only. Thus PLD is not fixed by the time the recovery plateau has been attained in growth medium, and this unfixed PLD can still be repaired when cells are shifted to conditioned medium. To study the kinetics of fixation of PLD (without hypertonic saline), the survival of cells incubated in growth medium for up to 9 h postirradiation was compared with that for cells incubated in growth medium for different times followed by incubation in conditioned medium. These results show that the damage was neither fixed nor misrepaired in growth medium but rather remained unrepaired for up to 2 h, and that damage fixation in growth medium does not begin until after 2 h and is completed by 6 h postirradiation. PMID- 7871153 TI - Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. AB - The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (> 10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10(4) PY Gy (EAR/10(4) PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to > 1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk about 1.10 Gy. PMID- 7871154 TI - Prevalence rate of thyroid diseases among autopsy cases of the atomic bomb survivors in Hiroshima, 1951-1985. AB - To examine the radiogenic risk of latent thyroid cancer, thyroid adenoma, colloid/adenomatous goiter and chronic thyroiditis, the data for 3821 subjects collected in the course of autopsies of atomic bomb survivors in Hiroshima from 1951 to 1985 by the Radiation Effects Research Foundation (RERF) were analyzed using a logistic model. About 80% of the autopsies were performed at RERF and the remainder at local hospitals. The frequencies of the above diseases were not associated with whether the underlying cause of death was cancer. However, note that our results may be influenced by potentially biasing factors associated with autopsy selection. The relative frequency of latent thyroid cancer (greatest dimension < or = 1.5 cm but detectable on a routine microscopic slide of the thyroid gland) increased as the radiation dose increased and was about 1.4-fold greater at 1 Gy than in the 0-Gy dose group. The relative occurrence of thyroid adenoma also increased as radiation dose increased, and was about 1.5-fold greater at 1 Gy than in the 0-Gy dose group. Sex, age at the time of the bombing or period of observation did not significantly modify the radiogenic risks for thyroid adenoma or latent thyroid cancer. No statistically significant association was found between radiation exposure and the rates of colloid/adenomatous goiter and chronic thyroiditis. The possible late effect of atomic bomb radiation on the frequency of benign thyroid diseases is discussed on the basis of these data. PMID- 7871155 TI - The equal effectiveness ratio: a quantitative approach to the evaluation of compounds for boron neutron capture therapy. AB - The resurgence of interest in boron neutron capture therapy (BNCT) as a potential treatment for glioblastomas and melanomas has resulted in a quest to identify and synthesize candidate compounds which can physiologically target the 10B atoms to tumor cells. Numerous boron-carrying compounds are now available and awaiting evaluation. Because the products of the boron neutron capture (BNC) reaction generally contribute greater than 50% of the dose in BNCT, the evaluation of the efficacy of boron compounds would be more precise if it were possible to remove, quantitatively, the dose contributed by the external reactor radiations. The purpose of this study is to report a method which does just that, i.e., leaves for precise evaluation the biological effect that is ascribable to the BNC products only. The evaluation involves a series of separately quantifiable factors, the product of which provides an overall "figure of merit" for the compound. PMID- 7871157 TI - Deduction of the clonogen content of intestinal crypts: a direct comparison of two-dose and multiple-dose methodologies. AB - A microcolony assay was used in conjunction with fractionated gamma irradiation to determine the number of clonogens in murine intestinal crypts with varying doses of irradiation used in the determination. The experimental design allows direct comparison between two-dose methodologies, employing one and two (or two or four) equal dose fractions, and multiple-dose methodologies involving determination of the crypt survival curves for a number of fractionation regimens using equal doses per fraction. The two-dose methodology yielded estimates of clonogen number of between 3 and 4 at low delivered dose (single and double fractions each of 6.5-7.5 Gy), rising to around 40 at high biological doses (two and four fractions each of 5.75 or 6.5 Gy). The multifraction methodology yielded estimates of clonogen number which increased from 13 after a single fraction to values of 26 and 22 after three and four fractions. However, the latter values were reduced to 11 and 9, and showed little evidence of any dependence on fraction number, when data pertaining to high biologically effective doses were excluded. Hence it is concluded that the high values for clonogen number typically deduced from such multiple-dose protocols, compared with the generally lower (but dose-dependent) values obtained from two-dose protocols, may be explained at least partially by the higher biological doses generally employed in the multiple-dose protocols. PMID- 7871156 TI - Liver toxicity induced by combined external-beam irradiation and radioimmunoglobulin therapy. AB - High-dose radiation therapy for liver metastases of gastrointestinal malignancies might be improved by combining external-beam irradiation and radioimmunoglobulin therapy. We studied the liver toxicity of the proposed combination in healthy beagle dogs. A total dose of 30 Gy to the whole liver, delivered in 2-Gy fractions over 3 weeks, resulted in mild, temporary veno-occlusive disease (VOD) in three of three dogs. Reversible bone marrow damage was noted after two intravenous injections of 18.5 MBq of yttrium-90-labeled monoclonal antibody ZCE025 per kg body weight in three of three dogs. Administrations of the antibody were separated by 1 week. Three dogs treated by irradiation of the liver with radioimmunoglobulin therapy added during the last 2 weeks of the irradiation showed signs of radiation hepatitis (VOD) starting around 35 days after treatment. One dog had a complete recovery, and two dogs were euthanized in a stage of terminal liver failure around day 90 after treatment. Temporary bone marrow damage was observed after the combined treatment, similar to the bone marrow damage observed after radioimmunoglobulin therapy alone. Earlier studies in the same dog model showed that bone marrow is the dose-limiting organ if radioimmunoglobulin therapy is used alone. The addition of irradiation of the liver to radioimmunoglobulin therapy changes the dose-limiting organ from bone marrow to liver. The radiation hepatitis observed in dogs is very similar to that observed in humans and is reflected in early platelet consumption in the irradiated liver plus late elevations of liver enzymes and VOD in central hepatic veins on histological analysis. Future applications of combined liver irradiation and radioimmunoglobulin therapy in humans should use radioimmunoglobulin therapy agents which show minimal uptake by normal liver. PMID- 7871158 TI - Gamma irradiation of the fetus damages the developing hemopoietic microenvironment rather than the hemopoietic progenitor cells. AB - Hemopoiesis is the product of two components: the hemopoietic tissue and the regulatory stromal microenvironment in which it resides. Plutonium-239, incorporated during fetal development, is known to cause deficient hemopoiesis. A predetermined equivalent gamma-ray dose has now been used in combination with cross-transplantation experiments to separate these two components and define where the damage arises. It was confirmed that 1.8 Gy gamma irradiation at midterm gestation caused a 40% reduction in the hemopoietic stem (spleen colony forming) cell population of their offspring which persisted to at least 24 weeks of age. Spleen colony formation after sublethal doses of gamma rays reflected this reduced complement of endogenous stem cells. The regulatory hemopoietic microenvironment, measured as fibroblastoid colony-forming cells, was similarly depleted. Normal growth of the CFU-S population after transplantation into standard recipients showed that the quality of the stem cell population in the offspring of irradiated mothers was not affected. By contrast, when used as recipients of a bone marrow transplant from either normal or irradiated offspring, the offspring of irradiated mothers were unable to support normal growth: there was a twofold difference in the number of CFU-S per femur for at least 100 days after transplantation. There were 70% fewer CFU-F in the femur 1 month after bone marrow transplantation when the offspring of irradiated mothers were used as transplant recipients compared to when normal offspring were used. This not only confirmed their reduced capacity to host normal stem cells but also indicated that CFU-F in the transplant were unable to compensate for the poor microenvironment in the irradiated offspring hosts. It is concluded that irradiation at midterm gestation damages the developing regulatory microenvironment but not the hemopoietic stem cell population that it hosts. PMID- 7871159 TI - Effect of fetal exposure to ultrasound on the behavior of the adult mouse. AB - Pregnant Swiss albino mice were exposed to diagnostic ultrasound (3.5 MHz, 65 mW, ISPTP = 1 W/cm2,ISATA = 240 W/cm2) for 10, 20 or 30 min on day 14.5 (fetal period) of gestation. Sham-exposed controls were studied for comparison. Any changes in physiological reflexes (such as pinna detachment, opening of the eyes and development of fur), postnatal mortality and changes in adult behavior (open field test, dark/bright arena test, hole board test and conditioned-avoidance test) were recorded. No change was observed in the physiological reflexes. The postnatal survival was also not affected significantly by the exposure. However, there were significant alterations in behavior in all three exposed groups as revealed by the decreased locomotor and exploratory activity and the increase in the number of trials needed for learning. These results indicate that ultrasound exposure during the early fetal period can impair brain function in the adult mouse. PMID- 7871160 TI - Modification of radiation sensitivity by salts of the metals beryllium and indium and the rare earths cerium, lanthanum and scandium. AB - The LD50 of 46 salts of metals and rare earths (lanthanoids) was determined in mice. Half the LD50 of the compounds was then combined with lethal radiation (10.5 Gy) and the modification of survival time was scored. Only the metals beryllium and indium and the rare earths cerium, lanthanum and scandium displayed activity in our assay. They were then tested at a wider range of lower doses and reduced survival time in a dose-dependent fashion. This appears to be compatible with enhancement of radiation sensitivity. The interaction of these metals and rare earths with radiation adds a new facet to their toxicological spectrum and, by enhancing radiation effects, may influence estimates of risk. On the other hand, the radiosensitizing properties of the metals may be useful for further development of compounds to be used as adjuncts in specific situations of cancer radiotherapy. PMID- 7871161 TI - Paramagnetic molecular centers in gamma-irradiated aluminum hydroxide complexed with glycine or serine. AB - Paramagnetic molecular centers produced by gamma irradiation at 77 K and at 293 K in Alx(OH)y, when precipitated with glycine or serine, were studied by ESR spectroscopy. Stable paramagnetic centers characteristic for the amino acid were observed only in the complexes with DL-alpha-serine, and only in air. In the absence of air, at 293 K, none of the paramagnetic centers gave ESR spectra characteristic of the amino acids examined. Irradiation at 77 K produced the glycine radical, .CH2COOH, only in the complex prepared at pH 6.8 and not in the complex prepared at pH 9.5. The radical decayed when the sample was warmed. In the serine complexes, at 77 K the radicals characteristic of the amino acid were not observed. Differences in the behavior between glycine and serine in the complexes prepared under similar conditions are probably due to the serine OH group available for hydrogen bonding in the matrix. PMID- 7871162 TI - Real-time, in vivo measurement of radiation dose during radioimmunotherapy in mice using a miniature MOSFET dosimeter probe. AB - This report presents the first real-time measurement of absorbed radiation dose during radioimmunotherapy in mice. Dose rate and total dose at the center of the tumor were measured after administration of 90Y-labeled antibodies using a miniature metal oxide semiconductor field-effect transistor radiation dosimeter probe which was inserted into the center of the tumor volume. Continuous real time measurements were made for as long as 23 h after injection of the radiolabeled antibodies. Comparison of the real-time dose-rate measurements with estimates based on the MIRD formalism indicates good agreement. The real-time measurements are further compared to measurements made in a second experiment in which groups of mice were sacrificed at individual times after injection of the same radiolabeled antibodies. The real-time measurements agree well with the measurements in excised tumors. The real-time measurements have greater time resolution and are much more efficient than traditional uptake measurements. PMID- 7871163 TI - Whole-body irradiation transiently diminishes the adrenocorticotropin response to recombinant human interleukin-1 alpha. AB - Recombinant human interleukin-1 alpha (rhIL-1 alpha) has significant potential as a radioprotector and/or treatment for radiation-induced hematopoietic injury. Both IL-1 and whole-body ionizing irradiation acutely stimulate the hypothalamic pituitary-adrenal axis. We therefore assessed the interaction of whole-body irradiation and rhIL-1 alpha in altering the functioning of the axis in mice. Specifically, we determined the adrenocorticotropin (ACTH) and corticosterone responses to rhIL-1 alpha administered just before and hours to days after whole body or sham irradiation. Our results indicate that whole-body irradiation does not potentiate the rhIL-1 alpha-induced increase in ACTH levels at the doses used. In fact, the rhIL-1 alpha-induced increase in plasma ACTH is transiently impaired when the cytokine is administered 5 h after, but not 1 h before, exposure to whole-body irradiation. The ACTH response may be inhibited by elevated corticosterone levels after whole-body irradiation, or by other radiation-induced effects on the pituitary gland and hypothalamus. PMID- 7871164 TI - Biological effects of carbon ions with medium energy on plant seeds. AB - The biological effects of 46.6 MeV/u 12C6+ ions on four kinds of plant seeds were studied at the Heavy Ion Research Facility in Lanzhou (HIRFL), Institute of Modern Physics (IMP), Academia Sinica. The results show that germination of the seeds is inhibited by exposure to ions. In root tip cells of irradiated seeds, a great variety of chromosomal aberrations were observed. Sensitivities in terms of inhibition of germination and induction of chromosomal aberrations in the four species are correlated. PMID- 7871166 TI - Principles and imaging of spinal instrumentation. AB - This articles focuses on the principles of spinal surgery, the basic types of spinal instrumentation, and imaging of the postoperative spine. It is the first of three articles in this issue that discuss the spine. Complications are discussed and illustrated throughout. This article should assist radiologists in the review of spinal, chest, and abdominal films of spinal surgery patients. PMID- 7871165 TI - Comments on "Analysis of survival of C-18 cells after irradiation in suspension with chelated and ionic bismuth-212 using microdosimetry" by Stinchcomb and Roeske (Radiat. Res. 140, 48-54, 1994) PMID- 7871167 TI - Fixation techniques and instrumentation used in the cervical spine. AB - This article emphasizes the techniques and instrumentation used in the cervical spine to provide insight into the identification and function of the fixation, grafting, and wiring techniques used for stabilization and fusion. Fracture reduction and stabilization in degenerative disease, the most common reasons for spinal fixation in the cervical spine, are discussed, as are infections, spinal stenosis, and tumors. PMID- 7871168 TI - Fixation techniques and instrumentation used in the thoracic, lumbar, and lumbosacral spine. AB - The radiologist is faced with continual changes in both surgical techniques and instrumentation for the spine. To properly evaluate radiographic and special imaging studies, it is necessary to have a working knowledge of the devices used and the principles that direct their use. This article discusses the identification and function of the most common instrumentation in the thoracic, lumbar, and lumbosacral spine. PMID- 7871169 TI - Total hip replacement and other orthopedic hip procedures. AB - The history of total hip replacement including that of the Girdlestone procedure and resurfacing procedures is discussed. An overview of total hip replacement and its indications and complications forms the bulk of this section. Also, the use of porous-coated prostheses and endoprostheses as well as pins and plates is discussed and illustrated. PMID- 7871170 TI - Imaging of the total knee arthroplasty. AB - We have reviewed the essentials of TKA imaging. Because the purpose of a knee arthroplasty is to relieve pain and improve function, radiographs should be viewed in the context of these goals. PMID- 7871171 TI - The radiology of total shoulder replacement. AB - The indications for total shoulder replacement and the radiologic evaluation prior to the operation are discussed in depth in this article. Different approaches to clinical problems are also discussed and illustrated, as are normal findings. This is followed by a discussion of the complications of shoulder reconstruction, including infection, fractures, and heterotopic bone formation. A review of the results is also given followed by a brief mention of a number of other orthopedic shoulder devices and plates. PMID- 7871172 TI - Hand and wrist. AB - Some basic principles of orthopedic management of common conditions of the hand and wrist have been presented. These basic principles and an awareness of the potential complications should aid radiologists in evaluation of postoperative films. The interested reader is referred to Green's Operative Hand Surgery and Chapman's Operative Orthopaedics for more detailed information. PMID- 7871173 TI - Replacement of "other" joints. AB - Replacement of larger joints other than the hip and knee has been relatively disappointing and remains in a developmental stage. In the small joints, initial enthusiasm for silicone rubber arthroplasty has diminished in all sites except the MCPs because of the recognition of the high frequency of silicone synovitis. Further research and development is ongoing. This article was intended to facilitate understanding of the choices of operative procedures, the types of available components, and particularly, the specifics of radiographic assessment of the success or failure of these "other" prostheses. We hope this information will be helpful in assessing postoperative radiographs, as "We only see what we look for and we only look for what we know." PMID- 7871175 TI - The radiology of bone allografts. AB - Bone allograft surgery provides an attractive and effective solution to many orthopedic problems. Nevertheless, the entire process is technically demanding and associated with many potential complications of which infection is one of the most difficult to treat. Many advances have been made in the procurement and use of bone allografts, and further investigation should expand the applications of allograft surgery and continue to diminish the incidence of complications. PMID- 7871174 TI - Radiology of devices for fracture treatment in the extremities. AB - This article describes the appearance and application of various mechanical devices used in the treatment of fractures. It is intended to familiarize the reader with the biologic and biomechanical principles underlying the design and application of particular devices as well as to explain and demystify some of the orthopedic vocabulary used to describe them. Once a fracture has been recognized and treatment has begun, the role of the radiologist in the management of the patient shifts from diagnosis to follow-up. The purpose of the radiologic report is no longer the detection, localization, and description of the fracture but, rather, the description of the mode and progress of treatment and surveillance for the occurrence of complications. It is therefore important for the radiologist to be familiar with the application and normal radiologic appearance of devices used in the treatment of fractures. PMID- 7871176 TI - Orthopedic complications. AB - This overview of the complications encountered in orthopedic cases focuses on, among other things, complications of spinal surgery. The incidence of infection in spinal instrumentation and other orthopedic procedures is discussed and followed by a review of the complications of total joint replacement. Finally, a few words on the radiologist's responsibility for the reporting of orthopedic complications are given. PMID- 7871178 TI - Catheter ablation of the accessory pathways of the Wolff-Parkinson-White syndrome and its variants. AB - The basis of arrhythmias in the Wolff-Parkinson-White (WPW) syndrome and its variants is the presence of accessory atrioventricular connections. Those variants include the concealed form of the WPW syndrome, the permanent form of junctional reciprocating tachycardia, and Mahaim preexcitation. In all forms of symptomatic WPW syndrome, catheter ablation of the accessory atrioventricular connections using radiofrequency current has become the treatment of choice. This review traces the development of this therapy, outlines the basics of the technique, summarizes the results reported in the largest series, indicate remaining areas of controversy, and discusses the indications and limitations of radiofrequency ablation therapy. PMID- 7871177 TI - Ablative therapy for atrioventricular nodal reentry arrhythmias. AB - Recent studies in the clinical electrophysiology laboratory have advanced our understanding of the physiologic anatomy of the atrioventricular (AV) junction and have helped direct new curative techniques for the treatment of AV nodal (junctional) reentry. In most patients, it appears that the AV node or the inputs to the AV node that constitute the "slow" pathway are located caudal to the compact AV node and His bundle region near the os of the coronary sinus. In contrast, conduction over the "fast" pathway appears to be located along the anterior tricuspid annulus proximal to the traditional His bundle recording position. This physiologic heterogeneity has allowed the development of curative techniques for AV nodal reentry. The current preferred technique involves ablation of the slow pathway by delivering radiofrequency lesions in the region of the coronary sinus ostium. Although several different localization techniques have been developed, the overall success rate for the procedure developed, the overall success rate for the procedure includes a primary success rate that should be over 95%, a 5% to 10% late recurrence rate, and a complication rate of under 2%. Complete heart block as a complication of slow AV nodal pathway ablation is rate but can occur. The improvements in the results of radiofrequency ablation for the treatment of AV nodal reentry have resulted in the increased use of this procedure clinically. It is now reasonable to offer young patients AV nodal modification as primary therapy for AV nodal reentry and to apply the technique in all age groups to drug-resistant patients. PMID- 7871179 TI - Cost-effectiveness analysis in heart disease, Part III: Ischemia, congestive heart failure, and arrhythmias. AB - Cost-effectiveness analyses were reviewed in the following diagnostic and treatment categories: acute myocardial infarction (MI) and diagnostic strategies for coronary artery disease (CAD), coronary artery bypass graft (CABG) surgery, percutaneous transluminal coronary angioplasty (PTCA), congestive heart failure (CHF), and arrhythmias. In the case of acute MI, coronary care units, as presently used, are rather expensive but could be made much more efficient with more effective triage and resource utilization; reperfusion via thrombolysis is cost-effective, as are beta-blockers and angiotensin-converting enzyme (ACE) inhibitors post-MI in appropriate patients. Cost-effectiveness of CAD screening tests depends strongly on the prevalence of disease in the population studied. Cost-effectiveness of CABG surgery depends on targeting; eg, it is highly effective for such conditions as left-main and three-vessel disease but not for lesser disease. PTCA appears to be cost-effective in situations where there is clinical consensus for its use, eg, severe ischemia and one-vessel disease, but requires further analysis based on randomized data; coronary stents also appear to be cost-effective. In preliminary analysis, ACE inhibition for CHF dominates, ie, saves both money and lives. Cardiac transplant appears to be cost-effective but requires further study. For arrhythmias, implantable cardioverter defibrillators are cost-effective, especially the transvenous device, in life threatening situations; radiofrequency ablation is also cost-effective in patients with Wolff-Parkinson-White syndrome apart from asymptomatic individuals; and pacemakers have not been analyzed except in the case of biofascicular block, where results were variable depending on the situation and preceding tests. PMID- 7871180 TI - [Phenotypic transition of smooth muscle cell and the expressional regulation of the caldesmon gene]. PMID- 7871181 TI - [Ocular dominance plasticity--a critical review]. PMID- 7871182 TI - [Microtubules and the regulation of plant form]. PMID- 7871183 TI - [Protein motion of cytochrome P450 in membranes and cellular response and signaling]. PMID- 7871184 TI - [Petroleum production by microorganisms]. PMID- 7871185 TI - [A method for separation of DL-amino acids]. PMID- 7871186 TI - [Present and future development of scientific instruments in Japan: an essay by a person in charge of the issue in a manufacturer]. PMID- 7871187 TI - [50 years after Anne Frank: reactive of a transgenerational trauma in countertransference]. AB - Traumatizations suffered in the course of the atrocities perpetrated by the National Socialists defy symbolization and, if unresolved, are passed on to subsequent generations. With reference to the psychoanalytic treatment of a forty year-old homosexual of the "second generation", the author traces the problematic of the transgenerational handing-down of unresolved traumatizations. The son of a Jewess whose brother was murdered in a concentration camp, the patient had to stand in for his lost uncle and remained caught up in a "symbiotic illusion" with this omni-present/absent object and with the mother, thus being unable to attain to a personality of his own and achieve the Oedipal triad. The article concentrates entirely on this case and provides an impressive record of the mechanisms of transference and counter-transference involved and the various stages of the psychoanalytic process. PMID- 7871188 TI - [The second Holocaust: life is threatening]. AB - According to the author's observations, the "second holocaust" is a phenomenon encountered both in the first and the second generation. This dramatic concept seeks to convey the fact that the devastations of the actual holocaust are re enacted and unconsciously repeated by the survivors and their children in terms not only of the content of the trauma but also of its style. Referring to a number of potted case histories, the authors describe how inevitable and absolute the shadow of destruction is felt to be by the victims and how the contrive to survive under this shadow. From a therapeutic viewpoint it appears helpful to encounter the onset and the effects of this "second holocaust" by activating the life side of the life-death dichotomy as a counter against the compulsive urge for repetition. Life, through felt itself to be permanently at risk, must be made to function as the motor for the negation of death. PMID- 7871189 TI - [Wounds that do not heal. Extreme traumatization in puberty]. AB - For the surviving victims, the persecution of the Jews by the National Socialists represents a form of traumatization so extreme as to beggar comparison with any other kind of traumatic event, say, a natural catastrophe. Interviews with people caught up in the machinery of persecution as adolescents have revealed to the author that they were subject to psychic lesions with devastating consequences hardly susceptible to adequate description in the framework of traditional psychoanalytic trauma theories. In puberty the internal separation process from the parents as love-objects is in itself difficult enough. When this is compounded with an external persecution situation the threat to a sound physical and psychic constitution is infinitely greater. In concurrence with other authors, and in particular with Keilson's concept of sequential traumatization, Gassler places particular emphasis on the transgenerational aspect of extreme traumatization. PMID- 7871190 TI - [Fragmented psychotherapy of a boy returned from Bergen-Belsen]. AB - Like an artist giving expression to his vision of reality, the psychoanalyst is also guided by a certain vision of psychic reality. With reference to the case of an orphan boy who survived Bergen-Belsen, the author traces the difficult process of attaining empathy with a vision of reality marked by the years spent in a concentration camp and the world of unimaginable horrors experienced there. After a long period of silence in which a relationship of trust was gradually built up, the young man found it possible to find expression for his un-utterable experiences, his unrest in the unconscious. The word Bergen-Belsen had become utterable. PMID- 7871191 TI - [Patients with tetanus from South-eastern Poland in material from the Clinic of Infectious diseases in Krakow in the years 1963-1992]. AB - The incidence of tetanus is more frequent in South-Eastern Poland than other areas of the country. The patients are treated in Clinic of Infectious Diseases in Cracow. Our observations concern 869 patients of the last 30 years. In the years 1963-1972 young patients prevailed and the mortality rate was 28% in the years 1983-1992. 15% of the patients were below 50 years of the age and 44% were above the age of 70. The mortality rate in the latter period (the third decade) increased to 42%. The increase in the age of the patients is explained by the introduction of immunization against tetanus and the mortality rate increase by the greater frequency of respiratory failure and other complications of the disease and treatment in elderly patients. PMID- 7871192 TI - [Coronary risk factors in a group of patients with insulin dependent diabetes mellitus--examination of the EURODIAB IDDM Complications Study Krakow]. AB - Cardiovascular complications are the main cause of disability and deaths in insulin dependent diabetic patients. The main aim of the EURODIAB IDDM Complications Study was to assess the prevalence of diabetes complications and of risk factors of these complications. In this study the data on cardiovascular diseases and their risk factors in patients included in the EURODIAB IDDM Complications Study--Krakow are presented. The study population included insulin dependent clinic attenders, aged 15-60 years, diagnosed before the age of 36 years. A random sample of up to 140 patients stratified by age, sex and duration of diabetes was chosen. Within each centre the study population consisted of all eligible IDDM patients living in a defined catchement area, who had attended the center at least once during the preceding 12 months. The studied sample included 120 patients (61 men and 59 women). Mean (sd) age of patients was 34.0 (9.6) years, mean duration of diabetes 14.2 (9.8) years, mean Hb A1c concentration 6.6 (1.5)%. The prevalence of cardiovascular diseases was assessed using standardized questionnaire and resting electrocardiogram. Blood pressure was measured with "random zero" sphygmomanometer. Electrocardiogram was assessed according to Minnesota code. Serum cholesterol and triglyceride concentration were determined by enzymatic methods. Albumin excretion rate was determined in 24 hours urine collection. Albumin concentration was assayed by immunoturbidimetry. Cardiovascular diseases were observed in 8.3% of patients. Arterial hypertension (WHO dfn) was found in 11.7% of patients, systolic blood pressure > or = 140 mm Hg in 9.2% of patients and diastolic blood pressure > or = 90 mm Hg in about 5% of men and 2% of women. Hypercholesterolemia (serum cholesterol > or = 6.5 mmol/l) was found in about 20% of patients, hypertriglyceridemia (serum triglyceride 2.2 mmol/1) in 16.4% of men and 10.2% of women. 41.0% of men and 28.8% of women were current cigarette smokers. Microalbuminuria (defined as albumin excretion rate 20-200 micrograms/min) was observed in 23% of men and 15.3% of women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871193 TI - [Receptor mechanisms of antiepileptic drug action]. AB - The recent findings on pathogenesis of epileptic seizures indicate their disturbance in balance between excitatory and inhibitory processes in neurocytes. Important neurotransmitters, of excitatory or inhibitory activity, are: gamma aminobutyric acid, glutamate and aspartate. The neurotransmitters act by activation of specific receptors: GABA-A, GABA-B, NHDA receptors, quis and kain. The receptor mechanisms of important antiepileptic drugs are discussed. The recent research on new antiepileptic drugs include those enhancing neuronal inhibition, and those diminishing neuronal excitation. PMID- 7871194 TI - [Dialysis adequacy and nutrition]. PMID- 7871195 TI - [Endothelins. I. Synthesis, receptors, action]. PMID- 7871196 TI - [Clinical probes using tumor necrosis factor in treatment of neoplastic diseases]. AB - Tumor necrosis factor-TNF is a cytokine that is predominantly produced by the activated macrophages. It was shown that TNF has the antineoplastic activity in vitro or in tumor xenografts on the animals in vivo. Clinical trials phase I and II carried out in many centers assessed toxic effects of TNF administration, as well as its pharmacokinetic and therapeutic effect. The following paper is a survey of the results of clinical trials which could be useful for the assessment of TNF role in oncological immunotherapy. PMID- 7871197 TI - [Archives regarding health services in II Republic in reserved New Act Archives in Warsaw]. PMID- 7871198 TI - [Exhibition of paintings from Docent Wladyslaw Laszczak]. PMID- 7871199 TI - [Late prognosis of patients after myocardial infarction complicated by atrioventricular conduction disorders]. AB - The purpose of the study was to follow-up postmyocardial infarction patients with atrioventricular conduction disorders complicating the acute phase of the disease. The study population consisted of 42 patients, 30 men and 12 women, aged 42 = 91 years (x = 65.2 +/- 12.6). Inferior and anterior myocardial infarction developed in 28 and 16 patients, respectively. The follow-up ranged from 1 to 5 years (x = 3.6). Within the first year there were 14 deaths, and 28 patients had control check-up. All the patients were submitted for physical examination, routine electrocardiography, 24-hr continuous ECG recording. At 1 year none of the patients developed new conduction disorders, whereas 71.4% of the patients revealed arrhythmias in ECG recording. Within 5 years there were 20 deaths (47.66%). A group of those who died, when compared with survivors was characterized by higher mean age, significantly more frequent presence of arterial hypertension and prior myocardial infarction. PMID- 7871200 TI - [Renovascular hypertension--clinical observations and long-term follow-up]. AB - Renovascular hypertension is one of the most common causes of secondary hypertension. Its early diagnosis is particularly important, firstly because it is one of the few potentially reversible causes of chronic renal failure. In many centers, including our own, renal angioplasty (PTA) or surgery is the treatment of choice for patients with renovascular hypertension. The aim of the study was the evaluation of the early and late results of PTA versus renovascular surgery. The diagnostic procedures and clinical course of renovascular hypertension were also analyzed. Among patients with renovascular hypertension treated in our Department during the 1981-1993 years, 89 patients (46 men, 43 women) were diagnosed and having renovascular hypertension (3% of all hypertensive patients). The average duration of hypertension in this group was 5 years. High incidence of accelerated hypertension (18%) and cardiovascular complications were observed: myocardial infarction in 20.2% of cases and stroke in 4.5%. The presence of renal failure was found in 22.5% of cases, hypokalemia in 11.2%, 38.3% of patients had changes in other arteries. Renal angioscintigraphy and captopril renal scintigraphy were performed in accordance with renal arteriography in 80% of patients. Arteriography showed unilateral renal artery stenosis in 78.7% of patients and bilateral - in 21.3%. The most common cause of renovascular hypertension in our material was atherosclerosis (65.2%). Fibromuscular dysplasia and Takayasu arteritis were diagnosed less frequently (25.8% and 9.0% respectively). Forty four patients were treated with PTA, 15 underwent surgical revascularization and 11 - unilateral nephrectomy. Early beneficial therapeutic effect (normalization or improvement of blood pressure control) was observed in 88.6% for PTA and 66.7% for surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871201 TI - [Levels of cadmium in serum of patients with chronic renal failure]. AB - The aim of the study was obtain answers the following questions: 1. Are serum cadmium concentrations in patients with chronic renal failure (CRF) different from levels in healthy subjects? 2. Are serum concentrations of above mentioned metal different between haemodialysed and non-haemodialysed patients. 3. Are serum cadmium concentrations changing during haemodialysis? 66 patients with chronic renal failure (42 patients treated with haemodialysis and 24 non haemodialysed patients) and 16 healthy subjects were observed. The blood samples in non-haemodialysed patients and healthy subjects were withdrawn only after cannula had been inserted into the antebrachial vein. The blood samples in haemodialysed patients were withdrawn four times: just before dialysis, during haemodialysis (in one hour of dialysis just in front of dialyser and just behind one) and after haemodialysis. Cadmium concentrations in serum in all examined group and cadmium concentrations in dialysis fluid and in demineralised water were measured by flame atomic absorption spectrophotometry. No significant changes were observed in serum cadmium concentration between patients with CRF and healthy subjects. Cadmium-concentration in non-haemodialysed patients was significantly higher than in haemodialysed patients. During haemodialysis a significant increase of serum cadmium level was observed. CONCLUSIONS: 1. Serum cadmium concentration in patients with CRF and in healthy subjects are not statistically different; 2. No significant changes in cadmium concentration between uraemic group patients were found; 3. Haemodialysis influences significantly on cadmium concentration. PMID- 7871202 TI - [Changes in levels of noradrenaline and adrenaline in blood after exercise testing and transesophageal atrial pacing in patients with ischemic heart disease]. AB - 13 patients with ischaemic heart disease and 8 healthy subjects underwent exercise testing and transesophageal atrial pacing. Alternations in plasma noradrenaline, adrenaline as well as systolic and diastolic blood pressure were determined. Mean plasma noradrenaline significantly increased after exercise effort in both groups of patients and it significantly correlated with the increase in systolic blood pressure. The essential increase in mean plasma noradrenaline was found after atrial pacing but the degree of increment was significantly higher after the exercise testing in both groups. The plasma adrenaline level showed a significant increase only during exercise in the ischaemic group. Considering to a more noticeable adrenergic response it can be concluded that exercise test is a more helpful method in diagnosis of ischaemic heart disease than transesophageal atrial pacing. PMID- 7871203 TI - [Effect of furosemide added to peritoneal dialysis fluid on hydroxyproline excretion in dialysate and urine]. AB - The effect of furosemide (1500 mg/21 of peritoneal dialysis fluid) on excretion of hydroxyproline in dialysate and its renal clearance was investigated in 12 patients with end-stage renal disease on regular dialysis treatment. The 37 +/- 8% and 20 +/- 6% increase of D/S ratio of hydroxyproline after 5 and 8 hours of dwell, respectively, and 52 +/- 24% increase of renal clearance of hydroxyproline were induced by furosemide, which indicate its significant influence on peritoneal and renal removal of hydroxyproline. PMID- 7871204 TI - [Clinical significance of heat shock proteins. Influence of heat shock proteins on the pathomechanism of selected diseases]. AB - The presentation shows the survey of diseases the pathogenesis of which might be connected with the existence of Heat Shock Proteins (HSPs). We discuss the data referring to the influence of the HSPs upon the occurrence and progression of the following diseases: systemic lupus erythematosus, reactive arthritis, rheumatoid arthritis, insulin dependent diabetes mellitus, schizophrenia and Alzheimer's disease. There is also indicated a possible activity of HSPs in the pathogenesis of neoplasia, organ ischaemia and inflammation or degeneration. PMID- 7871205 TI - [The role of prevention in osteoporosis]. AB - Prevention of osteoporosis plays the major role in care of osteoporotic patients because of limited efficacy of therapy in late stages of the disease. Prevention ought to begin the whole life and its main aims are: achieve maximal peak bone mass, stabilize bone mass in adults and slow bone loss in elderly. The most important are: long-term high diet calcium consumption, physical activity avoiding secondary reasons of osteoporosis and wide use of hormone replacement therapy. PMID- 7871206 TI - [Posterior urethral valve--etiology, diagnosis and treatment]. AB - The problems concerned the etiology, diagnosis treatment of the posterior urethral valves (PUV) were described. The malformation is found in boys and creates multi-infra cystic barrier symptoms during miction. USG examination is very helpful in the diagnosis of PUV, as well as micturating cysto-urethrography and urodynamic examination. In differential diagnosis of PUV, one must take into account the barrier causes in the following portions of the urinary tract: narrowing of the urethral exit anterior urethral valves, polyps, diverticuli, hypertrophy of the seminal cumulus. Surgical treatment includes valvular electro resection, laser destruction, widening by the use of Fogarty catheter and Foley catheter ended with a NaCl solution filled balloon. PMID- 7871207 TI - [Case of Aperts'-Crouzon syndrome in a 6-year old boy]. AB - A congenital disorder syndrome defined by literature as the Alperts'-Crouzon has been described for a six-year-old boy. Introduction of this case seems to be justified noting the rarity of its occurrence. PMID- 7871208 TI - [Case of ventricular fibrillation recorded during Holter monitoring and initiated by ventricular parasystole]. AB - A case of ventricular fibrillation during holter monitoring is described. Tape analysis doesn't shows any significant changes of QT intervals, increasing in heart rate and ventricular ectopic activity. It was attempt possibility that modulated parasystole may lead to ventricular fibrillation. PMID- 7871209 TI - [Maximilian Leon Cercha (1860-1927]. PMID- 7871210 TI - [Situational and individual determinants of change in emotion of surgical patients]. AB - The article presents the results of the study on the determinants of changes in emotion intensity in surgical patients. It is shown that the changes in intensity of anxiety--depression and anger are the result of the interaction of situational factors (time of operation) and personal individual predispositions (emotional reactivity). PMID- 7871211 TI - [Acceptance and subjective evaluation of intensive insulin therapy and an educational program by pregnant women with insulin dependent diabetes]. AB - The study was carried out in 71 IDDM female diabetics: 51 pregnant women aged 28.6 +/- 3.6 yrs, and 20 IDDM female patients aged 26 +/- 5 yrs. All women had been treated with intensified insulin therapy and continuous self-monitoring. All the patients participated in the five day educational programme at the beginning of therapy. The patients were requested to fill in a multiple-choice test questionnaire with questions about their knowledge of the practical aspects of diabetes, effectiveness of the educational programme, difficulties and acceptance of management. The diabetic pregnant women gave subjective estimations of the development of their children. Mean ratio of correct answers to 7 questions estimating the level of knowledge of diabetes was in diabetic pregnant patients 70% which was higher than in other IDDM female patients. 27% IDDM pregnant women estimated the course as very difficult. The main causes of difficulties in management in the investigated patients were self-estimating control of diabetes, dietary programme, frequent selfmonitoring. The majority of diabetic pregnant women (82%) and all IDDM females could and did accept the whole management programme. In conclusion the general aspects of management were accepted both by diabetic pregnant and non-pregnant women. The major difficulties were realisation of dietetic management and often estimations of glycemia during selfmonitoring of diabetes. The short, five-day educational course is beneficial in the IDDM management. PMID- 7871212 TI - [Radiologic methods of evaluating colonic transit time in functional disorders of the large intestine]. AB - Based upon literature and personal experience the authors review radiological techniques of evaluating colonic transit time in functional disorders of the large intestine. The distribution of given per os markers in the whole colon indicates prolonged transit time, which takes place in constipation of colonic inertia type. In the case of markers accumulation in the distal segment of the large intestine we encounter functional constipation of outlet obstruction type. The authors believe that colonic markers studies, easy to perform and non invasive for the patient should be carried out in order to obtain full information about defecation disorders. PMID- 7871213 TI - [Rare angiographic image of fetal ischiadic arteries in a 60 year old female. Case report]. PMID- 7871214 TI - [Morquio-Brailsford syndrome in two sisters]. PMID- 7871216 TI - [Selected aspects of diagnosis and treatment of cardiac arrhythmias. Invasive and noninvasive methods in diagnosis of cardiac arrhythmias]. AB - The paper summarizes the use of current technique in the diagnosis of cardiac arrhythmias. The value of non-invasive 24-hr continuous ECG monitoring and signal averaged electrocardiography has been discussed. The predictive value of circadian changes in RR intervals (HRV) in 24-hr ECG recording was emphasized in patients after myocardial infarction. HRV below 50 ms leads to a 5-fold increase in the risk of death within 3 months after myocardial infarction. The value of signal-averaged ECG in predicting sudden death ion patients after myocardial infarction is also independent of other techniques. Abnormal signal-averaged ECG was found to be a sensitive indicator of susceptibility to sustained ventricular tachycardia. Electrophysiology testing as one of invasive technique, was discussed with respect to its indications and usefulness in selecting non pharmacological treatment of cardiac arrhythmias (implantation of antiarrhythmic devices, radiofrequency ablation). PMID- 7871217 TI - [The Cochrane collaboration. Invitation for cooperation]. PMID- 7871215 TI - [A case of long-lasting foreign body in the submandibular and pterygo-mandibular space]. AB - Authors reported a case of a foreign body in the 70-years old man, located in the submandibular and pterygo-mandibular space in the left side. The case is worthy of notice because of a long-lasting treatment in the period previous to admission to the hospital department, and because of not explained cause and way of the introduction to the tissues of a facial skeleton. PMID- 7871218 TI - Immunosuppression in myelo-and lymphoproliferative disorders. PMID- 7871219 TI - Immunocompromised children with cancer. PMID- 7871220 TI - Immunosuppression in radiotherapy. PMID- 7871221 TI - Diagnostic imaging in the hematologic immunocompromised patient. PMID- 7871222 TI - Pulmonary mycosis in patients with hematologic malignancies. PMID- 7871223 TI - Pulmonary aspergillosis in patients with hematologic malignancies: clinicoradiologic correlation. PMID- 7871224 TI - Myelo- and lymphoproliferative disorders: evaluation of hepatosplenic infiltrates and role of US-CT-guided aspiration biopsy. PMID- 7871225 TI - Diagnostic imaging of intracranial and spinal lymphomas. PMID- 7871226 TI - CNS radiochemoprophylaxis in children with acute lymphoblastic leukemia. Neurotoxicity and diagnostic imaging. PMID- 7871227 TI - Changes in leukocyte and lymphocyte distribution after radiation therapy directed to the pelvis, mediastinum and chest-wall. PMID- 7871228 TI - Opioids and Their Receptors: Cloning and Beyond. Proceedings of the 25th International Narcotics Research Conference (INRC). North Falmouth, Massachusetts, 16-21 July 1994. Abstracts. PMID- 7871229 TI - [XXX Congress of the Brazilian Society of Tropical Medicine Salvador-Bahia, 6-11 March 1994. Abstracts]. PMID- 7871230 TI - Nonambulatory persons with profound mental retardation: physical, developmental, and behavioral characteristics. AB - Although profound mental retardation is generally associated with various organic etiologies that result in substantial cognitive and behavioral deficits, little is known about specific subgroups of persons with profound mental retardation. This study presents data on the physical, developmental, and behavioral characteristics of a group of 203 nonambulatory persons with profound mental retardation residing within a specialized service setting. The results indicate that nonambulatory persons with profound mental retardation have a high prevalence of physical and medical problems along with high rates of self injurious, stereotypic, and aggressive behavior. Assessment results from the Stanford-Binet (L-M), Bayley Scales of Infant Development-Mental Scale, and Vineland Adaptive Behavior Scale reveal a high degree of variability in cognitive and adaptive functioning. However, developmental age-equivalent scores of cognitive ability, communication, daily living, socialization, and motor skills for the group fell below the 1-year level. The data illustrate the complexity of needs in providing habilitative services to nonambulatory persons with profound mental retardation. PMID- 7871231 TI - The effects of cue control relaxation on adults with severe mental retardation. AB - This study was designed to assess two aspects of behavioural relaxation training with subjects who have severe mental retardation. The first was whether or not cue words could be linked effectively to training so that they would eventually produce a relaxation effect in the absence of a full relaxation procedure. The second was to determine the effects of relaxation training and subsequent cue control on concentration and attention to an occupational task. Five subjects participated, and individual case designs were used. Cue Control, behavioural relaxation training (BRT), and new therapists were introduced at different times for each subject to ascertain the effects of each variable. Subjects were assessed at baseline and following each training session on a behavioural relaxation scale to judge the direct effects of relaxation training and on the amount of time spent concentrating on an occupational task. BRT produced reductions in rated anxiety and improvements in concentration for all subjects. The cue control words were effective only after they had been linked to BRT. In most cases, the introduction of a new therapist had no appreciable effect on anxiety or concentration. There was some suggestion that in the final cue only phases concentration was better and more consistent than during the BRT phases of the study. PMID- 7871232 TI - Preference testing: a comparison of two presentation methods. AB - Paired and group presentation methods of preference testing were compared with eight learners with severe-profound developmental disabilities. Each presentation method was also compared with staff rankings of learners' preferences. Similar preferences were identified with both presentation methods. Although the paired presentation took more time to administer, it elicited more consistent preference information than the group presentation. Staff preference rankings were not highly correlated with either the group or paired presentation. However, items identified as most preferred by staff and by both presentation methods were similar. PMID- 7871233 TI - "What did you say?" Using review of tape-recorded interactions to increase social acknowledgments by trainees in a community-based vocational program. AB - Dana and Rick, two adults with developmental disabilities enrolled in a restaurant training program, had poor prospects for long-term employment because of inappropriate social behavior. They often made no response, mumbled inaudibly, or made a negative remark when spoken to by their supervisors or other employees. Each trainee's Individual Vocational Plan (IVP) included goals of prompt and polite acknowledgement of coworker initiations. Previous efforts to improve Dana and Rick's acknowledging behavior had been unsuccessful. Throughout the study, each trainee's responses to 20 verbal initiations by coworkers (i.e., requests, questions, corrective feedback, praise, and social comments) were recorded during each of two observation periods per workshift. Throughout one of the observation periods during the intervention phases, the trainees carried in their work aprons a small, audio cassette recorder that recorded their interactions with coworkers. The primary intervention consisted of a preworkshift meeting in which the trainee and experimenter reviewed five randomly selected interactions recorded during the previous day's shift. The review included self-evaluation, praise, corrective feedback, and role-play. A multiple baseline across subjects design showed each trainee acknowledged a greater number of coworker initiations as a function of the intervention. Each trainee also acknowledged more coworker initiations during the second observation period when the tape recorder was never worn. In a subsequent intervention phase, Dana reviewed her tape-recorded interactions prior to randomly selected shifts. Rick's acknowledgments increased to a socially valid level when the review procedure was supplemented with graphic feedback. Both trainees continued to acknowledge their coworkers' initiations at levels equal to nondisabled restaurant employees when they no longer wore the tape recorder during a final phase and during follow-up observations 4 to 8 weeks later. PMID- 7871234 TI - Validity of the schizophrenia diagnosis of the psychopathology instrument for mentally retarded adults (PIMRA): a comparison of schizophrenic patients with and without mental retardation. AB - The Psychopathology Instrument for Mentally Retarded Adults (PIMRA) was designed to assess psychiatric disorders among mildly and moderately mentally retarded persons. In a psychiatric population without mental retardation (n = 53), the PIMRA schizophrenia scale had an internal consistency coefficient alpha = 0.52. By removing one outlier item this increased to alpha = 0.61. By comparing the PIMRA schizophrenia diagnoses with DSM-III-R diagnoses in the psychiatric population, we found an external reliability corresponding to phi = 0.47 and an unweighted kappa = 0.43. Weighting of the mistakes resulted in a weighted kappa (w) = 0.74. A regression analysis of DSM-III-R diagnosis based on the PIMRA items was conducted. The regression equation was able to identify 75.5% of the DSM-III R schizophrenic disorders in the psychiatric population. This equation correctly identified 75.5% of the PIMRA schizophrenias in a mentally retarded population. The intermethod reliability was phi = 0.49. We also compared the 38 psychiatric patients with DSM-III-R schizophrenic disorder with the 48 mentally retarded patients with PIMRA schizophrenic disorder. The mentally retarded patients had less delusions and more incoherence and flat affect. They also used less neuroleptic drugs. PMID- 7871235 TI - A long-term follow-up of treatment for severe self-injury. AB - One of the shortcomings in the literature is the paucity of long-term follow-up reports of the treatment of self-injury and other destructive behavior, particularly of treatment involving contingent shock. This is a report of a long term follow-up of treatment for a woman with severe mental retardation and severe self-injurious behavior (SIB) treated initially with the Self-Injurious Behavior Inhibiting System (SIBIS) in brief clinical trials. Programmed generalization and maintenance procedures consisted of treatment throughout all waking hours in all settings as well as during brief sessions. Significant reductions attained in the SIBIS clinical trials generalized to the natural environment and the brief follow up sessions; however, rates began to climb in the natural environment until a SIBIS pairing procedure could be applied more consistently as a consequence of self-injury. Contingent shock was discontinued after month 30 of follow-up. Overall rates of SIB episodes in the natural environment were reduced from an average of 24.6 per month in the 7 months prior to the SIBIS clinical trials to less than 2 per month during the 72 months of follow-up. Rates in brief treatment sessions remained low during the entire follow-up period. Implications of these results are discussed. PMID- 7871236 TI - New shuttle vector for cloning in Bacillus stearothermophilus. AB - Cloning vector plasmid pRP9 was constructed on the basis of the broad host-range plasmid pLM6. pRP9 was a small plasmid (2.9 kb), possessed a convenient polyrestriction site sequence and efficiently transformed Bacillus subtilis, Bacillus stearothermophilus and Escherichia coli. Furthermore, pRP9 presented a very high segregational stability in Bacillus hosts. Also, the structural stability in Bacillus strains, grown under selective pressure, of pRP9 carrying a 3-kb fragment, was high. No single-stranded and high-molecular weight pRP9 DNA was found in B. stearothermophilus. The host/vector systems described possessed all the properties required for efficient gene cloning. PMID- 7871237 TI - Flagellin gene profiling of Helicobacter pylori infecting symptomatic and asymptomatic individuals. AB - Diversity within and around the flagellin (fla) A gene of Helicobacter pylori was studied by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) analysis and genomic Southern blot hybridization profiling. Four distinct pattern types were identified by DdeI restriction analysis of the 1.5-kb flaA amplicon of 55 strains. Most strains (73%) had the same flaA RFLP type, but subtypic variation was evident in some strains. No consistent associations were observed for selected strain subsets between the DdeI flaA profiles and phenotype (motility and cytotoxicity), urease gene profile or patient symptomatology. A subset of seven (F-1 profile) and four (F-2 profile) strains with identical HindIII digest patterns provided further evidence that the flaA gene was relatively highly conserved within H. pylori. By contrast, the flaA gene blot hybridization profiles were more diverse and consistent with greater variation at restriction sites in adjacent regions of the genome. We conclude that analyses of polymorphisms within the flaA gene provide limited discrimination between strains of H. pylori. The flaA genomic blot profiles offer greater potential for molecular typing purposes, although no associations with other pathogenicity factors or disease symptoms could be deduced. PMID- 7871238 TI - Polymerase chain reaction using arbitrary primer for the design and construction of a DNA probe specific for Porphyromonas gingivalis. AB - In this work, we used a novel approach for the design and construction of DNA probes which requires no knowledge of target DNA sequence. We demonstrated that species-specific genetic markers, identified as such among monomorphic, randomly amplified DNA segments generated by the polymerase chain reaction with arbitrary primer can be labelled to yield so-called "anonymous probes". We report here on the construction of such an anonymous probe, 1146 bp long, specific for the Gram negative anaerobe Porphyromonas gingivalis, a suspected major etiologic agent of chronic periodontitis in adults. PMID- 7871239 TI - Nested polymerase chain reaction for detection of Legionella pneumophila in water. AB - A highly sensitive nested polymerase chain reaction (PCR) method was evaluated for detection of Legionella pneumophila in water. Two sets of primers homologous to the coding region of the L. pneumophila macrophage infectivity potentiator (mip) gene were used. Even when starting from minute amounts of L. pneumophila DNA, the double PCR products were readily detected by direct visualization in ethidium-bromide-stained agarose gels. The method was tested on 34 potable water samples from a hospital building and compared with standard culture isolation. L. pneumophila was isolated in only twelve samples, whereas, by nested PCR, 19 samples were positive, 12 of them coincidental with culturing. These results indicate that nested PCR permits detection of L. pneumophila in samples where culturing fails, with the advantage of a rapid turnaround time, simplicity and the ability to detect non-culturable cells, fulfilling the requirements of sensitivity and specificity for routine use in an environmental laboratory. PMID- 7871240 TI - The LPS localization might explain the lack of protection of LPS-specific antibodies in abortion-causing Chlamydia psittaci infections. AB - Four monoclonal antibodies against chlamydial lipopolysaccharide (LPS) were used to study their localization and distribution in the Chlamydia psittaci AB7 abortion-causing strain by immunoelectron microscopy. A non-embedding technique on whole chlamydiae, together with a post-embedding technique on McCoy cells infected with the strain, were performed. Immunogold labelling was observed on the surface of reticular bodies (RB), but not on elementary bodies (EB). Immunolabelling was observed in ultrathin sections on both sides of the external chlamydial membrane, mainly on the inner side of EB and on the outer side of RB. Immunogold density was higher in EB than in RB; however, the absolute number of gold particles was higher in RB than EB, suggesting a loss of immunolabelling during the transformation of RB into EB. Specific labelling of LPS was also found in electrodense and adielectronic vacuoles near the surface of the cytoplasmic membrane of infected McCoy cells. These results suggest that the lack of protection against some chlamydial strains, despite the presence of anti-LPS specific antibodies, is due to the localization of LPS on the inner side of the external membrane of EB. PMID- 7871241 TI - Survey of clinical isolates of diarrhoeogenic Escherichia coli: diffusely adhering E. coli strains with multiple adhesive factors. AB - A total of 335 Escherichia coli strains were isolated from sporadic cases of aqueous diarrhoea in patients hospitalized in Clermont-Ferrand, France, during 1991 and 1992. Many of these strains belonged to the diffusely adhering E. coli (DAEC) group, since 51 of them (15.2%) hybridized with the daaC probe corresponding to the accessory gene of the F1845 adhesin and 13 (3.9%) with the AIDA-I (adhesin involved in diffuse adhesion-I) structural gene. The other pathogenic E. coli groups were weakly represented: 0.6% (2 strains) of enterotoxigenic E. coli (ETEC), 0.6% (2 strains) of enterohaemorrhagic E. coli (EHEC) and 3.9% (13 strains) of enteroaggregative E. coli (EAggEC). Neither enteropathogenic E. coli (EPEC) nor enteroinvasive E. coli (EIEC) were isolated in our study period. Among the DAEC strains studied, we described two major surface proteins of 16 and 29 kDa. We showed that the 16-kDa protein (CF16K) was involved in adhesion in vitro to Caco-2 and HEp-2 cells. Pretreatment of bacteria with anti-CF16K serum or of Caco-2 cells with purified CF16K greatly decreased the adhesion of the E. coli CF1085 strain producing the CF16K protein to both cell types. The CF16K adhesive factor was found in 9.5% (33 strains) of the 335 E. coli strains studied by colony immunoblot assays with anti-CF16K serum. Twelve strains producing CF16K hybridized with the daaC probe, indicating that the CF16K is not related to the Dr family adhesins which recognized the Dr blood group antigen as receptor. The 29-kDa protein, isolated from 9 strains out of the 335 studied (5.1%), was identified as the CS31A antigen by Western blot assay using anti-CS31A serum and by hybridization experiments with a CS31A DNA probe. This antigen is routinely observed in septicaemic or enterotoxigenic bovine E. coli strains. We showed that a single diarrhoeogenic E. coli strain could harbour at least two adhesive factors, since 36% of CF16K E. coli strain producers and 68.4% of CS31A E. coli strain producers hybridized with the daaC DNA probe. PMID- 7871242 TI - Molecular relationship of an atypical Azospirillum strain 4T to other Azospirillum species. AB - DNA/DNA hybridization, plasmid content and partial 16S rDNA sequence were determined to confirm the relationship between two Azospirillum strains, 4B and 4T, isolated from the same rice rhizosphere. The partial 16S rDNA sequence was determined for 9 strains belonging to 5 Azospirillum species which included Azospirillum lipoferum strains 4B and 4T, and was compared to a set of ribosomal sequences from other bacteria of the alpha subdivision of the Proteobacteria. Four Azospirillum species sequences were found to form a coherent group, whereas A. halopraeferens was found to be more divergent. The five Azospirillum species were closely related to Magnetospirillum and to a lesser extent to Rhodospirillum, with which they share some morphological features. The partial 16S rDNA sequences of the two strains 4B and 4T were identical and confirmed the closeness of these two strains. Plasmid content and DNA/DNA hybridization data (S1 nuclease and delta Tm) grouped Azospirillum strains 4B and 4T with the other strains of species Azospirillum lipoferum (USA5a, 59b, BR17). Other biochemical and genetic characters confirmed the grouping of Azospirillum strains 4B and 4T together with A. lipoferum. PMID- 7871243 TI - A comparison of direct and indirect (oscillometric) measurements of arterial blood pressure in anaesthetised dogs, using tail and limb cuffs. AB - Oscillometric measurements of arterial blood pressure were compared with direct measurements in anaesthetised dogs being monitored during routine surgery. Readings were obtained with tail cuffs and limb cuffs and the reproducibility (precision) of the readings from various cuff sites was also compared in conscious dogs. Tail cuffs gave the best precision in conscious dogs and the closest correlation with direct measurements in anaesthetised dogs, especially for systolic pressure. The proximal hindlimb site gave results with a slightly lower precision. PMID- 7871244 TI - Effect of dietary composition on abomasal and duodenal myoelectrical activity. AB - The changes in the frequency of abomasal slow waves and their propagation, the abomasal spike burst rate and the duodenal spike burst rate were assessed in sheep fed three diets containing either 100 per cent concentrate, 50 per cent concentrate and 50 per cent forage, or 100 per cent forage. The frequency of abomasal slow waves and spike burst frequency were both significantly reduced in sheep fed the diets high in concentrate when compared with animals fed the 100 per cent roughage diet. The velocity of propagation of the slow waves and the duodenal spike burst frequency were not significantly affected by the dietary composition. The sheep consumed significantly less of the 100 per cent concentrate diet in the 45 minutes before recording than of the other two diets, but the amount of feed consumed was not correlated significantly with the changes observed in the myoelectrical activity. These are consistent with an inhibitory effect of concentrate on abomasal motility. PMID- 7871245 TI - Rate of discharge and morphology of sweat glands in the perineal, lumbodorsal and scrotal skin of cattle. AB - The rates of evaporation of moisture from the skin in the lumbodorsal, perineal and scrotal regions of cattle were measured in thermoneutral and high environmental temperatures. The rates of evaporation from the perineal and scrotal regions of heifers and bulls were significantly (P < 0.001) greater than those from the lumbodorsal areas. The lumbodorsal rate of evaporation increased significantly (P < 0.001) when cows and bulls were transferred from a thermoneutral to a hot environment and the rate of evaporation from the scrotum of bulls showed a similar increase; the rate of evaporation from the perineum of cows increased to a smaller extent (P < 0.05) under the same conditions. The rate of evaporation from the perineum of cows reached a maximum on the day of oestrus but the stage of the oestrous cycle had no effect on the lumbodorsal rate of evaporation. PMID- 7871246 TI - Effects of non-steroidal anti-inflammatory drugs on the hyperalgesia to noxious mechanical stimulation induced by the application of a tourniquet to a forelimb of sheep. AB - A tourniquet was used in conjunction with a mechanical threshold testing device to investigate the suitability of the technique for the investigation of analgesic drugs in sheep. The changes to the mechanical thresholds to noxious stimulation during and after the inflation of a pneumatic tourniquet on a limb were recorded, and the influence of pre-treatment with two non-steroidal anti inflammatory drugs was studied. Fentanyl, an opioid agonist with known analgesic properties in sheep, was used as a positive control. The tourniquet significantly reduced the mechanical thresholds on the ipsi- but not the contralateral limb. Pretreatment with either flunixin meglumine or carprofen attenuated the development of mechanical hyperalgesia, and fentanyl initially caused a significant anti-nociceptive effect. The time to aversion was not significantly different between the treatments. These results suggest that hyperalgesia induced by a tourniquet may be a useful technique for the investigation of the anti nociceptive effects of analgesic drugs in sheep. PMID- 7871247 TI - Genetic structure of populations of beta-haemolytic Lancefield group C streptococci from horses and their association with disease. AB - The genetic structure of beta-haemolytic Lancefield group C streptococci isolated from horses in Australia was examined by multilocus enzyme electrophoresis. The 249 isolates comprised 70 classified phenotypically as Streptococcus equi subspecies equi, 177 classified as S equi subspecies zooepidemicus and two which were unclassifiable. Forty-one electrophoretic types were identified which could be classified into three major clusters, A, B and C. Of the isolates, 178 fell into cluster B (types 4 to 22) and lay within a genetic distance of 0.36. Sixty nine of the 70 S equi subspecies equi isolates fell into type 12, which suggests that they were members of a single clone, and the isolates from abscesses were significantly more likely to belong to type 12 than those from horses with no clinical signs (P < 0.001). There were no other significant associations between electrophoretic types or clusters and the isolation of the organism from particular sites. These data suggested that S zooepidemicus may be the archetypal species from which the clone designated subspecies equi has been derived. If isolates of the subspecies equi from other geographical regions also prove to be members of electrophoretic type 12, this hypothesis would be strengthened. PMID- 7871248 TI - A study by flow cytometry of lymphocytes in sow colostrum. AB - Mammary secretions contain leucocytes which may be of value to the neonate. The cells obtained from sow colostrum (1 to 2.5 x 10(6) ml-1) are mainly lymphocytes (10 to 25 per cent) and epithelial cells (more than 20 per cent). In milk, there are few lymphocytes (0.5 to 2 per cent) and mostly alveolar epithelial cells. The study of lymphocytes in the mammary secretions of sows has been made difficult by the high proportion of epithelial cells, which could not be separated from lymphocytes, and by a high background in membrane immunofluorescence labelling. This paper describes a method for the study of the cells in the mammary secretions of sows by flow cytometry. It showed that 70 to 90 per cent of colostral lymphocytes were T lymphocytes, with T8 lymphocytes predominating over T4, and that the ratio T4/T8 was significantly lower in colostrum (0.57) than in blood (0.80). There were no lymphocytes expressing interleukin-2-receptors in the colostrum of sows. PMID- 7871249 TI - Developmental changes in testicular luteinising hormone receptors and androgens in the dog. AB - The changes with age in the levels of testicular luteinising hormone (LH) receptors in dogs, were correlated with plasma androgen concentrations and the effects of stimulation with human chorionic gonadotrophin (hCG). The presence of high-affinity binding sites for LH was demonstrated in the testes of all the animals studied, and the apparent affinity of the LH receptors did not change significantly with age. The total number of LH receptor sites per testis increased continuously with age and the growth of the testis. The major rise in the number of LH receptors occurred between six and 10 months of age, and coincided with the phase of rapid testicular growth. The concentrations of androstenedione, testosterone and 5 alpha-dihydrotesterone in plasma increased gradually until six months of age, and then increased rapidly with the increase in the number of testicular LH receptors. An increase in the concentrations of androgens in plasma was observed in response to stimulation with hCG after the number of testicular LH receptors began to increase progressively. The increase in the sensitivity of the dogs' gonads to LH could be responsible for the marked increase in the secretion of androgens which occurs during puberty in the male dog. PMID- 7871250 TI - A biochemical profile for predicting the chronic exposure of sheep to Microcystis aeruginosa, an hepatotoxic species of blue-green alga. AB - Sheep which grazed on the shoreline of a fresh-water lake which had a toxic bloom of Microcystis aeruginosa were studied for evidence of chronic poisoning, and a serum biochemical profile was developed to indicate sub-lethal, chronic poisoning in the sheep which had been exposed to microcystins. The profile included measurements of glutamate dehydrogenase (GLDH), gamma-glutamyl transferase (gamma GT), bile acids, bilirubin and albumin. Of 18 sheep which were exposed to M aeruginosa for more than three months, 100 per cent had high serum concentrations of bile acids, 94 per cent had high activities of GLDH and gamma GT, 83 per cent had high bilirubin and 72 per cent had low albumin concentrations compared with the median values of unexposed animals. Other sheep which were exposed for shorter periods, showed evidence of hepatic injury after one week of exposure. The majority of the sheep showed no preference for an alternative, uncontaminated source of water. PMID- 7871251 TI - Endotoxin-induced platelet aggregation in heparinised equine whole blood in vitro. AB - Endotoxaemia is a leading cause of death among horses. Thrombocytopenia is a common finding in clinical and experimentally-induced cases of endotoxaemia and can lead to coagulopathies, including disseminated intravascular coagulopathy which is usually fatal. In this study it was shown that endotoxin (3 ng ml-1 to 25 micrograms ml-1) can aggregate equine platelets in heparinised whole blood in vitro. The endotoxin-induced aggregation (EIA) was shown to be dependent on the presence of leucocytes in the blood and did not occur when detoxified endotoxin was used, suggesting that lipid A was necessary for the response. Aspirin (1 mmol litre-1) had no effect on EIA whereas apyrase (40 micrograms ml-1) completely abolished it and CV3988 (3 to 30 mumol litre-1) (a competitive antagonist of platelet-activating factor) inhibited the response in a concentration-dependent manner. It is concluded that endotoxin activates equine platelets at low concentrations through an indirect mechanism that involves calcium, leucocytes, adenine nucleotides and platelet-activating factor. PMID- 7871252 TI - Blood lactate disappearance after maximal exercise in trained and detrained horses. AB - The influence of training on blood lactate concentrations during treadmill exercise and a 40-minute inactive recovery period was examined in seven trained and seven detrained thoroughbred horses. Lactate concentrations were measured in venous blood collected at the end of each exercise state, and at intervals for 40 minutes afterwards. Measurements were made of maximum oxygen uptake (VO2max, ml kg-1 min-1), VLA4 (velocity at which blood lactate concentration was 4 mmol litre 1); LA8 (lactate concentration [mmol litre-1] during exercise at 8 m sec-1), peak lactate (highest lactate concentration after exercise), LA40 (lactate concentration 40 minutes after exercise), the time of peak lactate concentration (minutes after exercise) and the rate of disappearance of blood lactate (Rtd). The trained horses had a significantly lower LA8 (2.1 +/- 0.1 vs 6.5 +/- 1 mmol litre-1, P < 0.01), higher VLA4 (9.8 +/- 0.2 vs 5.8 +/- 0.6 m sec-1, P < 0.01) and higher VO2max (156.3 +/- 3.8 vs 107.1 +/- 3.9 ml kg-1 min-1, P < 0.001). The value of Rtd and the time of peak lactate concentration were not significantly different. PMID- 7871253 TI - Effect of chronic pain associated with lameness on plasma cortisol concentrations in sheep: a field study. AB - Plasma cortisol concentrations were measured in two groups of sheep taken from 29 flocks in north Devon. The first group were healthy adult females and the second group were adult females suffering from footrot in one forefoot. These sheep were assessed for the severity of the lesion and the level of lameness and assigned a score. The plasma cortisol concentration was significantly higher in the lame sheep than in the healthy sheep and remained so for up to three months after the apparent resolution of the clinical lesion. There was no correlation between the severity of the footrot and the concentration of plasma cortisol. PMID- 7871254 TI - Competency of blood coagulation in the newborn calf. AB - This study evaluated the haemostatic profiles of a group of 11 female and seven male calves from the day of birth until they were 60 days of age. Similar results were found for both sexes. At birth the plasma activity of the procoagulant proteins, Factors VII, VIII:C, IX, X and XI and fibrinogen were all close to the adult values. Factors VII, VIII:C and fibriogen increased transiently during the first seven days of life but the increases were not sufficient to influence routine coagulation screening assays such as the activated partial thromboplastin time and the prothrombin time. At birth, the plasma concentration of the protease inhibitor, alpha 2-macroglobulin, was approximately 50 per cent of adult values and increased slowly during the first seven days of life; the plasma concentration of antithrombin III was higher than that of alpha 2-macroglobulin. The changes in the plasma concentration of fibronectin paralleled the changes in fibrinogen and Factor VIII:C from birth to 60 days of age; the concentrations of total plasma protein and plasma albumin remained stable and within the adult ranges throughout the 60 days. The plasma concentration of glucose increased transiently during the first 48 hours after birth. PMID- 7871256 TI - Effect of chronic hypocortisolaemia on plasma cortisol concentrations during intravenous infusions of hydrocortisone sodium succinate in dogs. AB - Intravenous infusions of hydrocortisone sodium succinate (HSS) were given at 0.625 mg kg-1 hour-1 and 0.312 mg kg-1 hour-1 to six dogs. Plasma cortisol concentrations were measured by radioimmunoassay at 0, 15, 30, 45 and 60 minutes and then every 30 minutes for a further five hours. Chronic hypocortisolaemia was induced and maintained with mitotane and the HSS infusions were repeated after 31 and 50 days. No statistically significant difference was observed in the plasma cortisol concentrations after either period of hypocortisolaemia, but the plasma cortisol concentrations tended to be higher in most of the dogs. PMID- 7871255 TI - Osmotic fragility of erythrocytes in clinically normal dogs and dogs infected with parasites. AB - The osmotic fragility of the erythrocytes was measured in blood samples collected from randomly selected healthy and infected dogs at a dogs' rescue shelter. The dogs were classified into six groups on the basis of the final diagnoses from clinical, post mortem and laboratory findings. The minimum (less than 5 per cent) and maximum (more than 90 per cent) haemolysis of the erythrocytes of the clinically normal dogs (group 1), occurred in 0.60 per cent and 0.30 per cent solutions of sodium chloride (NaCl). For the non-anaemic hookworm-infected dogs (group 2a) the respective values were 0.8 per cent and 0.4 per cent NaCl, and for the anaemic hookworm-infected dogs (group 2b) they were 0.85 per cent and 0.5 per cent NaCl, respectively. The erythrocytes from dogs with Babesia canis (group 3), concurrent hookworm and B canis (group 4) and Ehrlichia canis infections (group 5) had minimum haemolysis in 0.75 per cent NaCl and maximum haemolysis at between 0.20 per cent and 0.35 per cent NaCl solutions. The derivative fragiligrams for groups 2a, 2b, 3 and 4 were shifted to the left, whereas the fragiligram for group 5 was similar to that for the clinically normal dogs (group 1). The left shift for the hookworm-infected dogs was due to the increased osmotic fragility of a minor sub-population of the erythrocytes, but for the dogs infected with B canis major sub-populations of the erythrocytes had an increased osmotic fragility. PMID- 7871258 TI - Pathology and residues in veal calves treated experimentally with clenbuterol. AB - Six veal calves were medicated with clenbuterol at 20 micrograms kg bodyweight-1 day-1 for 42 days before they were slaughtered, to evaluate the lesions and residues in target organs. Compared with six unmedicated calves the most noticeable changes were tracheal dilatation, decreased uterine weight, slight mucous hypersecretion in the uterus and vagina and depletion of liver glycogen. The highest concentrations of clenbuterol (62 to 128 ng/g-1) were recorded in the choroid/retina, and the aqueous humour had the lowest concentration (0.5 to 2.4 ng ml-1). The residue concentrations were higher than the maximum residue level set for clenbuterol (0.5 ng g-1). PMID- 7871257 TI - Expression of fibronectin and its integrin receptor alpha 5 beta 1 in canine mammary tumours. AB - Fibronectin and its integrin receptor alpha 5 beta 1 were studied by immunohistochemical methods in five normal canine mammary glands, four dysplastic glands and 18 mammary tumours. The aim of the study was to evaluate the possible changes in the alpha 5 beta 1 integrin receptor and its ligand fibronectin in relation to the metastatic capacity of canine mammary neoplasms. The immunostaining of alpha 5 beta 1 was very uniform in the hyperplastic glands but uneven in the mammary tumours. The expression of alpha 5 and beta 1 was diminished in metastatic tumours but there were some alpha 5-positive cells with pronounced features of malignancy and immaturity. Stromal fibronectin was increased in most cases and cytoplasmic staining of fibronectin was observed in epithelial and myoepithelial cells in mammary neoplasms but not in normal or dysplastic mammary tissue. There was no relationship between the content of alpha 5 beta 1 and the expression of fibronectin in canine mammary tumours. PMID- 7871259 TI - Pharmacokinetics of fluconazole in cats after intravenous and oral administration. AB - Fluconazole (100 mg) was administered to six adult cats as an intravenous infusion over 30 minutes, and the same cats received 100 mg of the drug orally 16 weeks later. The cats were bled repeatedly through an indwelling jugular catheter, the plasma fluconazole concentrations were assayed by high performance liquid chromatography, and the concentration-time data were subjected to a non compartmental pharmacokinetic analysis. The mean (SD) intravenous half-life (13.8 [2.6] hours) was similar to that observed after oral dosing (12.4 [3.0] hours). The plasma clearances (intravenous 0.9 [0.1], oral 0.9 [0.2] ml min-1 kg-1) and the volumes of distribution at steady state (intravenous 1.1 [0.1], oral 1.0 [0.1] litre kg-1) were also similar after the two routes of dosing. The peak plasma concentration was reached 2.6 hours after oral dosing and the drug was completely bioavailable (1.09 [0.05]). On the basis of this single dose study, the administration of 50 mg fluconazole every eight hours to a 4 kg cat should produce average steady state plasma fluconazole concentrations of approximately 33 mg litre-1. PMID- 7871260 TI - Changes in the blood composition of calves during experimental and natural infections with Eimeria alabamensis. AB - Two trials were carried out to assess the changes in blood composition of calves infected either experimentally or naturally with Eimeria alabamensis. In the first, 12 calves were dosed orally with 10 to 400 million sporulated oocysts and compared with three control calves. The second trial used eight calves turned out to graze a permanent pasture known to induce E alabamensis coccidiosis in calves and eight calves turned out on to a previously ungrazed pasture. In both trials the serum activities of glutamate dehydrogenase (GLDH) and alkaline phosphatase (AP) and the serum concentration of total bile acids decreased in the infected animals while total bilirubin increased. The changes in GLDH, bile acids and bilirubin were most pronounced just before the calves began to excrete oocysts. In the first trial the lowest AP activity was observed 10 days after infection, but in the second its activity continued to decrease throughout the trial. In the first trial haematology, serum fibrinogen, total protein and protein fractions were also investigated. All the significant changes were small and the potential of the investigated blood components as diagnostic markers is therefore minimal. PMID- 7871261 TI - Western blot analysis of the IgG response of sheep vaccinated with S48 Toxoplasma gondii (Toxovax). AB - The IgG antibody responses of sheep vaccinated by the subcutaneous injection of live tachyzoites of 'incomplete' strain S48 toxoplasma (Toxovax) were analysed by Western blotting. Antibodies corresponding to a range of tachyzoite antigens (13 to 48 kD) were detected, but the response was dominated by antibody recognising a 30 to 32 kD band. Unvaccinated ewes challenged orally with oocysts of the 'complete' M3 toxoplasma strain had a more complex IgG response that recognised antigens in six dominant bands of similar intensity as those in sheep vaccinated with S48 tachyzoites and then challenged with M3 oocysts. No differences were detected between the antigenic structures of the S48 tachyzoites and RH strain tachyzoites when the antigens were probed with immune ovine sera. Many of the anitgens of the S48 tachyzoites that were recognised had molecular weights similar to those of antigens that have been identified in other strains of toxoplasma. PMID- 7871262 TI - Ingestion of host immunoglobulin by three non-blood-feeding nematode parasites of ruminants. AB - Host immunoglobulin was detected in homogenates of adult worms or fourth stage larvae of Haemonchus contortus, Ostertagia ostertagi, O circumcincta and Dictyocaulus viviparus, but not in preparasitic third stage larvae of H contortus. All the worms had been washed in detergent before being homogenised to remove any immunoglobulin adhering to the cuticle. This procedure, the concentrations of immunoglobulin detected and observations on sections of the worms stained with fluorescent anti-sheep immunoglobulin, all suggested that the immunoglobulin had been ingested, even by the non-blood-feeding species. This finding suggests that the Ostertagia species and D viviparus may be susceptible to vaccination by the gut antigen approach, a method with considerable promise for blood-feeding parasites like H contortus and Boophilus microplus. PMID- 7871263 TI - Effect of Mycoplasma gallinarum on embryonated village chicken eggs. AB - The effect of Mycoplasma gallinarum isolated from village chickens on embryonated village chicken eggs was investigated. Seven-, 10-, 12- and 18-day-old embryos were inoculated with medium containing 10(6) colony forming units of M gallinarum or with uninfected medium and incubated at 37 degrees C until they hatched. There was no significant difference between the infected embryos which failed to hatch and those which hatched or between them and the group inoculated with medium only. A much higher percentage of the eggs inoculated as 18-day-old embryos hatched than of those inoculated at seven, 10 and 12 days old. The hatchability of the uninoculated village chicken eggs used in the four trials ranged from 60 to 100 per cent. Mycoplasmas were isolated from the oesophagus, trachea and yolk of the infected chicks and from the dead-in-shell embryos. PMID- 7871264 TI - Lincomycin and spectinomycin in the treatment of breeding rams with semen contaminated with ureaplasmas. AB - Ureaplasma species were isolated from semen samples collected sequentially from one Awassi and three Assaf breeding rams. Each ram was injected subcutaneously with an aqueous solution of lincomycin and spectinomycin for five consecutive days at a dose equivalent to 4.5 mg kg-1 lincomycin and 9.0 mg kg-1 spectinomycin daily. Serum and semen samples were collected at intervals during the treatment and assayed for lincomycin. No Ureaplasma species were isolated from semen samples collected during the course of the treatment and at intervals for 17 days after the last treatment. The concentration of lincomycin in semen ranged from 0.51 microgram ml-1 four hours after treatment to 0.08 microgram ml-1 24 hours after treatment, and these levels were three to nine times higher than the corresponding serum concentrations. PMID- 7871265 TI - [Mycoplasma infection with Stevens-Johnson syndrome and antiphospholipid antibodies: apropos of 2 cases]. AB - We report two cases of Mycoplasma pneumoniae infections associated with Stevens Johnson syndrome and antiphospholipid antibodies. Such an association has been noted once in the literature. The relationship between antiphospholipid antibodies and Stevens-Johnson syndrome and others cutaneous manifestations of infections diseases is discussed. Though mainly described in systemic lupus erythematosus and autoimmune diseases, anticardiolipin antibodies and lupus anticoagulant have been found in many infectious disorders. But in the latter conditions, they have been considered by many authors as "non pathogenic" or "non prothrombotic" on epidemiologic and immunologic data. We suggest that antiphospholipid antibodies could possibly play a role in their pathogenesis especially as the mechanisms are not to date clearly understood. PMID- 7871266 TI - [Gelatinous transformation of the bone marrow. Apropos of 3 cases]. AB - Gelatinous transformation of the bone marrow is a rare histological lesion usually associated with cachexia. The authors report three new cases, two in anorexia nervosa and the third in Hodgkin disease. A review of the literature underlines association with marrow cell necrosis and provides the most frequent etiologies. Pathogenesis of gelatinous transformation remains unclear and her prognostic depends on etiology. PMID- 7871267 TI - [Etiopathogenesis of non-insulin-dependent diabetes]. AB - Two major mechanisms, peripheral insulin resistance and impaired insulin secretion participate concomitantly but to a variable extent to the pathogenesis of non-insulin-dependent diabetes, whose heterogeneity, suspected for a long time, is now confirmed by the recent discoveries of the molecular biology. Mutations of several genes governing key-steps of the recognition of the glucose signal, insulin secretion or its peripheral effect have been found in some particular cases, but presently not at a large scale among non insulin-dependent diabetic patients. The tendency to worsening of the metabolic disturbances with the time, even under adequate therapy, can be explained by the vicious circle of glucose toxicity, but other mechanisms like amylin, responsible of the deposition of amyloid in the islets, may play a role. So, despite the acquisition of many new knowledges, the pathogenesis of non-insulin-dependent diabetes keeps nowadays a part of its mystery. PMID- 7871268 TI - [Diabetes mellitus and atherosclerosis. Physiopathology of diabetic macroangiopathy]. AB - Numerous prospective epidemiological studies point out high mortality prevalence in diabetic subjects. Classical risk factors, especially arterial hypertension and hypertriglyceridaemia, are abnormally associated with diabetes mellitus. However, they don't account for overall surmortality in this disease. Additional markers of cardiovascular risk appeared as albuminuria, abdominal obesity, and the couple insulinoresistance/hyperinsulinism. Physiopathological intrinsic mechanisms inherent to macroangiopathy are multiple and intricate (hemostatic disorders, endothelial impairments, oxidative stress, quantitative and qualitative lipoproteins abnormalities, part of hyperinsulinism and growth factors). Strict normoglycaemia and exacting control of all other risk factors is essential. Use of other therapeutic agents as antioxidants and antiagregants, is discussed. PMID- 7871269 TI - [Therapeutic intensification and hematopoietic stem cell autotransplantation in the treatment of solid tumors in adults: principles, realization and application to the treatment of germ cell, trophoblastic, breast, ovarian and small-cell bronchial tumors. 1]. AB - Autologous bone marrow transplantation for the treatment of solid tumors in adults remains an uncommon therapeutic approach. The feasibility of such high dose therapies is clearly proved, especially with the advent of hematopoietic growth factors and the rescue by the peripheral stem cells to reduce the duration of the chemotherapy-induced myeloid aplasia. The question is to exactly define the place of high-dose therapy in the land of solid tumors. For the treatment of primary chemoresistant gonadal germ-cell tumors, the possibility to cure the patients and the interest of high-dose therapy with autologous bone marrow transplantation are clearly demonstrated. As consolidation for the treatment of poor prognosis tumors, the place of high-dose therapies remains moot. For the treatment of chemoresistant extragonadal germ-cell tumors, especially for primary mediastinal tumors, the level of resistance to cisplatin-based chemotherapy regimens is generally too high to be overcome by intensive therapies given as single course or as tandem courses. However in association with debulking surgery, this therapeutic approach has to be considered for some patients. In the treatment of poor prognosis breast cancer, high-dose therapy with autologous bone marrow transplantation or with peripheral stem cells support is able to convert some patients with partial response into complete responders. However, the consequences on overall survival and on disease-free survival are not evident. For metastatic breast cancer and for poor-prognosis tumors (inflammatory breast cancer, axillary metastatic nodes > or = 8), the interest of high-dose therapy has to be determined by randomized studies. These studies are ongoing in USA and in Europe. For the treatment of poor-prognosis ovarian cancer, the situation is more difficult to appraise. Once again, randomized studies have to be done to precisely define the place of high-dose therapy. In the land of small-cell lung carcinomas, high-dose therapy is actually forsaken by most of authors, even for limited diseases. The results of previous studies are disappointing. Moreover, occult medullary micrometastases involvement is frequent, once again even in limited diseases. However new therapeutic associations, as the ICE regimen (IFM, Carboplatin, VP-16) delivered as single or tandem therapy, have to be studied, especially as early consolidation therapy for the treatment of limited small-cell lung carcinomas. PMID- 7871270 TI - [Cutaneovisceral leishmaniasis following severe nervous depression]. AB - Leishmania is considered an opportunistic agent during cellular immunodeficiency. The authors report the case of a patient living in the south of France presenting visceral leishmaniasis with cutaneous manifestations in the course of a severe nervous depression. This case report illustrates the possible relationships between stress and immunity. PMID- 7871271 TI - [Segmental myocarditis in Churg-Strauss syndrome. Review of the literature apropos of a case]. AB - We describe a 25-year old man in whom segmental myocarditis and pericarditis was diagnosed using two-dimensional echocardiography. Churg-Strauss syndrome was suspected in the presence of asthma and evidence of hypereosinophilia. Early therapy with oral prednisone led to resolution of pericarditis but septal hypokinesia was still present after 4 years. The pathophysiology of segmental myocarditis in the Churg Strauss syndrome is discussed. PMID- 7871272 TI - [Necrotizing hepatic granuloma of brucellosis origin. Apropos of a case]. AB - The authors report on a case of febrile necrotizing brucellosis hepatic granulomatosis in a patient living in brucellosis endemia areas. This hepatic localization of brucellosis is rare: to our knowledge only 28 cases have been described in the literature. The bacteriological diagnosis was not established by blood or abscess pus cultures, but by Brucella serology only. Surgery completed by biantibiotherapy have permitted a complete recovery. PMID- 7871273 TI - [Disulfiram (Esperal) toxicity. Apropos of 3 original cases]. AB - Prescribed since 1948 to control chronic alcoholism, disulfiram may cause severe toxicity as report in three cases of acute motive axonal polyneuritis. Disulfiram toxicity may present different clinical aspects: 1) Cytolytic hepatitis with fatal evolution in 30% of cases (fulminant hepatitis), and full recovery for the other 70%. The onset of the symptoms usually occurs as early as 15 days to a maximum of 6 months (most within 2 months) after initiation of treatment. 2) Severe optic neuritis with full recovery in 2 months. 3) Peripheral neuropathy usually dose dependent, with different clinical presentations: polyneuritis with sensory, motor, or both deficits, and few cases of tetraplegia. 4) Encephalopathy frequently associated with one of the precedent symptoms, having a favorable outcome (probably resulting in inhibition of dopamine-beta-hydroxylase by disulfiram). The mechanism of toxicity (direct or idiosyncractic) remain unclear. Disulfiram has been used safely in millions of people since 1948, and we have only few cases reports of severe toxicity. From a practical point of view, treated patients should benefit by a neurological examination once a month, ophtalmological examination every 2 months, and hepatic enzymes monitored twice a month during the 2 first months. This is the price to prevent and to detect side effects of disulfiram therapy. PMID- 7871274 TI - [White fingers]. PMID- 7871275 TI - [Increase of CA-19-9 and nephrotic syndrome: a case]. PMID- 7871276 TI - [Recurrent polymicrobial septicemia disclosing aortic paraprosthetic infection]. PMID- 7871277 TI - [A case of avian salmonellosis]. PMID- 7871278 TI - [Acute tuberculosis of the knee following intra-articular infiltration]. PMID- 7871279 TI - [Volume 50: here we are!]. PMID- 7871280 TI - [Clinical case of the month. Severe electrolyte disorders in anorexia nervosa]. PMID- 7871281 TI - [NO.: the double image of a new biological messenger. Introduction and biochemical aspects]. PMID- 7871282 TI - [Nitric oxide (NO.), a new therapeutic purpose]. PMID- 7871283 TI - [NO. and the central nervous system]. PMID- 7871284 TI - [Vascular effects of NO.. Roles of NO. in septic shock and adult respiratory distress syndrome (ARDS)]. PMID- 7871285 TI - [Moderate hypercholesterolemia and coronary disease: the MAAS study and the 4S study]. PMID- 7871286 TI - [Is there value in determining tumor markers in senology?]. PMID- 7871287 TI - [How I examine... an obese patient prior to a potential gastroplasty]. PMID- 7871288 TI - [How I treat... a patient with light or moderate cardiac insufficiency?]. PMID- 7871289 TI - [Surface biopsies and skin diseases]. PMID- 7871290 TI - Pre-participation physical evaluations. Development of uniform guidelines. PMID- 7871291 TI - Dietary requirements for ultra-endurance exercise. PMID- 7871292 TI - Weight training. A potential confounding factor in examining the psychological and behavioural effects of anabolic-androgenic steroids. AB - Psychological and behavioural changes are associated with anabolic-androgenic steroid (AAS) use. Changes in personality, moods and self-esteem following weight training have also been reported. The fact that nearly all AAS users are also dedicated weight trainers has often been overlooked in studies examining the relationship between AAS use and behavioural change. A triad may exist between AAS use, weight training and behavioural change (including dependence). It is also possible that changes frequently attributed to AAS use may also reflect changes resulting from the concurrent use of other substances such as alcohol, and from dietary manipulation including food supplements. Weight training and related practices should be considered potential confounding factors in future studies designed to examine the psychological and behavioural effects of AAS. PMID- 7871293 TI - Athletes and pain tolerance. AB - Athletes' attitudes towards pain, and the cognitive strategies they use while experiencing pain, may be reflected in their pain tolerance levels and their performance and adherence to sport injury rehabilitation. Association and dissociation are 2 of the more popular cognitive strategies, and most research has found that these strategies increase pain tolerance and performance. It has not clearly been established how these results are transferred to athletes overcoming the pain associated with injury rehabilitation. The major limitation of most of these pain induction techniques is that they are inherently safe, and individuals know that the induced pain can be terminated at any time. Not only will the stressor be terminated, but the pain experienced will also decline because the pain is due to the stimulation. Thus, it is possible that pain tolerance and performance levels are higher in experimental settings than would normally be in real-life situations. However, exercise-induced muscle soreness is one pain induction technique which attempts to alleviate this limitation and therefore provide more realistic levels of pain to tolerate. The pain, stiffness, prolonged reduction in muscle strength, and decreased range-of-motion that appear 24 to 48 hours after strenuous eccentric exercise does not fully subside until 8 to 10 days after the initial bout of exercise. Study participants experience long lasting, real-life pain. Thus, it is worthwhile for those involved in sport injury rehabilitation to be aware of the effectiveness of these cognitive strategies that may assist athletes to overcome the pain associated with exercise induced muscle soreness, and how this relates to rehabilitation. PMID- 7871294 TI - Effects of cross-training. Transfer of training effects on VO2max between cycling, running and swimming. AB - Cross-training is a widely used approach for structuring a training programme to improve competitive performance in a specific sport by training in a variety of sports. Despite numerous anecdotal reports claiming benefits for cross-training, very few scientific studies have investigated this particular type of training. It appears that some transfer of training effects on maximum oxygen uptake (VO2max) exists from one mode to another. The nonspecific training effects seem to be more noticeable when running is performed as a cross-training mode. Swim training, however, may result in minimum transfer of training effects on VO2max. Cross-training effects never exceed those induced by the sport-specific training mode. The principles of specificity of training tend to have greater significance, especially for highly trained athletes. For the general population, cross-training may be highly beneficial in terms of overall fitness. Similarly, cross-training may be an appropriate supplement during rehabilitation periods from physical injury and during periods of overtraining or psychological fatigue. PMID- 7871296 TI - [What is your diagnosis? M.A., detail radiography of the right elbow]. PMID- 7871297 TI - [Unstable angina pectoris: distress signal in coronary heart disease]. PMID- 7871298 TI - [Mechanisms of acute coronary syndrome]. AB - The pathogenesis of coronary artery disease is characterized by an increased vasoconstriction, activation of platelet vessel wall interactions as well as the invasion of monocytes into the subintima with deposition of lipids as well as proliferation and migration of vascular smooth muscle cells. In the acute coronary syndromes plaque rupture as well as activation of platelets and coagulation as well as coronary vasoconstriction play an important role. Clinically these mechanisms lead to unstable angina and myocardial infarction. For the understanding of acute coronary syndromes, the mechanisms operative in the healthy blood vessel wall are important. Healthy coronary arteries are in a constant state of vasodilatation, platelets as well as the coagulation cascade are inactivated and vascular smooth muscle cells of the media are quiescent. Endothelial mediators such as nitric oxide, prostacyclin and tissue plasminogen activators and other mediators play an important role in this regard. The continuous release of nitric oxide and prostacyclin keeps the coronary circulation in a state of vasodilatation and inhibits platelet vessel wall interaction. Other mediators of the endothelium also inhibit coagulation and migration and proliferation of vascular smooth muscle cells. On the other hand in patients with cardiovascular risk factors and possibly also in those with genetic disposition as well as with aging, these mechanisms are impaired and in turn increased vasoconstrictor responses of coronary arteries, activation of platelet vessel wall interaction, invasion of monocytes into the subintima with lipid storage and proliferation/-migration of vascular smooth muscle cells occur. A cause oriented therapy of coronary artery disease and of acute coronary syndromes in particular must be based on these pathophysiological mechanisms. PMID- 7871299 TI - [Pathological-anatomic basis of unstable angina pectoris]. AB - The primary trigger mechanisms leading to coronary artery disease are largely unknown; however, consensus has been reached that unstable angina pectoris is always associated with acute pathological and anatomical changes in a plaque, most commonly in the form of a plaque fissure or rupture involving the fibrous luminal cap with thrombosis, hemorrhage and dissection. Rupture almost always occurs at the weakest part of the fibrous cap and leads to exposition of extracellular lipids and matrix, necrotic tissue and lipid-laden foam cells. The exact mechanisms of plaque rupture are not entirely known; it is possible, however, that they do represent fatigue breaks in the tissue. The clinical consequences of these events are unstable angina pectoris and myocardial infarction. PMID- 7871300 TI - [Clinical aspects and classification of unstable angina]. AB - Unstable angina pectoris is a clinical syndrome with multiple underlying pathophysiologic mechanisms. This presentation is concerned with primary angina pectoris exclusively. In the majority of cases a rupture of an atherosclerotic plaque and an intracoronary thrombus are responsible for instable angina. The practitioner's role is to identify those patients who will develop complications with the aid of clinical parameters. Prinzmetal's angina is also instable, occurs at rest and leads to ST-segment elevation. It is most likely due to coronary spasm, developing in disease-free and atherosclerotic coronary segments alike. This variant of unstable angina is treated most successfully with calcium antagonists. The recognition of the responsible pathophysiologic mechanism permits adjustment of treatment of every patient taking into consideration the seriousness of his prognosis. PMID- 7871301 TI - [Unstable angina--diagnostic methods]. AB - The means available to the physician to secure diagnosis, to define risks and to decide on optimal treatment are reviewed. The history, the physical findings on admission and an electrocardiogram at rest form the essential basis for a first appreciation. Then follow non invasive investigations i.e. ergometry, myocardial radionuclide scan and a continuous ECG recording for 24 hours. These studies provide a good risk assessment. On the basis of the clinical assessment and the additional studies the necessity for a coronary angiography can be decided on in most instances. Coronary angiography is required prior to any percutaneous or surgical cardiac intervention. It has the disadvantage to be invasive and it requires a complex infrastructure. However, it has also become a safe procedure and it provides optimal risk assessment. PMID- 7871295 TI - Exercise and the immune system. Natural killer cells, interleukins and related responses. AB - The main methods for the evaluation of natural killer (NK, CD16+ CD56+) cells, interleukins and related subsets of lymphocytes are briefly described. Moderate endurance exercise causes either no change or an increase in lymphocyte and NK cell counts, total T cell (CD3+) count, the ratio of T helper (CD3+ CD4+) to T suppressor (CD3+ CD8+) cells, mitogen-induced lymphocyte proliferation, serum immunoglobulin levels and in vitro immunoglobulin production. Plasma levels of interleukin-1 increase but interleukin-2 (IL-2) levels generally fall. Decreases in plasma IL-2 levels reflect increased expression of beta (CD122) receptors for IL-2, and thus increased binding of IL-2, changes in cell distribution or a lesser production of IL-2 by peripheral blood mononuclear cells. Exercise to exhaustion induces adverse changes in many of these indices of immune function, particularly if the physical activity is accompanied by psychological or environmental stress. Moderate, appropriately graded training reduces the adverse reactions initially associated with a given bout of exhausting exercise, and cross-sectional comparisons show an increased expression of beta IL-2 receptors on the peripheral blood mononuclear cells of trained individuals. However, excessive training, nutrient deficiency and/or muscle damage has adverse consequences for both the production of interleukins and the response of the immune system to these cytokines. PMID- 7871302 TI - [Drug treatment of unstable angina pectoris using nitrates, beta blockers and calcium antagonists]. AB - Endothelial dysfunctions, nonocclusive coronary thrombi and plaque ruptures cause unstable angina pectoris, an instability of coronary artery disease and are accompanied by an increased risk of sudden death and acute myocardial infarction. Clinical factors, angiography and newer laboratory measurements help to identify patients who should be assigned to surgical or interventional revascularization or to medical therapy. In contrast to revascularization procedures, medical therapy is available everywhere at any time. Monotherapy either by use of betablockers or calcium antagonists can not be recommended while nitrates are a cornerstone in medical therapy for unstable angina. Nitrates in combinations with betablockers and calcium antagonists have been shown to reduce the number and duration of ischaemic episodes. These combinations also reduce the incidence of acute myocardial infarction, sudden death and the need for surgical revascularization. PMID- 7871304 TI - [Long-term results in bone marrow transplantation]. PMID- 7871303 TI - [What is your diagnosis? Amotile achalasia]. PMID- 7871305 TI - [The many-colored picture of endocrine crisis in clinical practice--psychological symptoms in hormonal emergencies]. AB - Four case reports from a general practitioner's daily work illustrate the problem of endocrine crises hidden by psychiatric symptoms. Psychologic and psychiatric problems in a GP's office are very frequent; endocrine crises are very rare, but with high consequences for the patient. Optimal coordination and cooperation between psychiatric and somatic clinicians and investigation are necessary for optimal education of future physicians. PMID- 7871306 TI - [Pseudo-sciatica of neoplastic origin: apropos of an unusual case]. AB - The authors report a case of 'pseudosciatic' pain due to bone metastasis located in the sacroiliac joint secondary to breast cancer. Complementary investigations are mandatory in any case of sciatic pain starting at 80 years of age, even in the absence of the usual criteria suggesting a neoplastic origin. In this case our investigations revealed sacroiliac bone metastasis from the breast, explaining the clinical picture. Primary and secondary sacral tumors are uncommon. Their clinical manifestations are unspecific, consisting mainly of low back pain and sciatic pain. CT scan and MRI are the best tools to evaluate these lesions. Conservative management, combining radiotherapy and hormonal treatment, has been effective in terms of both pain and function. PMID- 7871307 TI - [Sources of error in the pre-analytical phase of blood gas analysis]. AB - Analysis of blood gases and blood pH yield important information in many situations of clinical emergencies. We report on a patient in whom pre-analytic errors in blood gas and blood pH measurements resulted in unnecessary further investigations. We therefore studied various pre-analytic sources of error in blood pH and blood gas analysis. Delay in sample processing for more than one hour resulted in an increase of pO2 and pCO2 and a decrease of pH. Excess sodium heparin solution as an anticoagulant (> or = 10% of total volume) led to a significant decrease of pH and pCO2 and to an increase of pO2. Air bubbles (10% of total volume) left in the syringe for 10 min significantly increased pO2. For accurate estimations of pO2, pCO2 and pH, it is necessary to keep the heparin solution below 10% of total volume, to expel all air bubbles from the syringe and to process the blood sample within one hour. Instructions to medical staff on handling blood samples for blood gas analysis should include these possible sources of errors. PMID- 7871308 TI - [Night sweats: observation on a not unusual phenomenon]. AB - With the aid of an impressive case report, the authors describes the diagnostic clues for the understanding of sweating during the night hours. Many internistic and psychological disorders may cause heavy sweating during night hours. But also substances used by patients dietary habits as well as excessive intake of alcohol may be involved. The therapeutic approaches are numerous and are discussed at the end. PMID- 7871309 TI - [A case from practice (318). 1. Constrictive pericarditis. 2. Alcoholic hepatopathy]. PMID- 7871310 TI - Qualification in physical medicine and rehabilitation. Acknowledgment of an expanding speciality. PMID- 7871311 TI - Trauma to arteries of the forearm. AB - Trauma to arteries of the forearm corresponds to 20% of total arterial trauma. The authors analyzed 24 patients with non iatrogenic trauma of the forearm arteries, cared for from January 1987 to December 1990. All patients were male, trauma by penetrating instrument was the most frequent, with 21 cases (87.5%), absence of pulses was the most frequent clinical manifestation (62.5%), fifteen patients did not present ischemic manifestations (54.2%) and half of the patients did not exhibit neurological symptoms. Injury to only one artery was found in 11 cases, five of them in the radial artery (20.8%), five in the ulnar artery (20.8%) and one in the interosseous artery (4.2%). Concurrent injury to the radial and ulnar arteries was found in 13 cases (54.1%). Regarding nervous impairment, injury to the radial nerve was found in four cases (16.6%) and of the median and ulnar nerves, one case in each (4.1%). All patients with concurrent injury to the ulnar and radial arteries (13) were submitted to arterial restoration. The 11 patients with injury to a sole artery of the forearm were managed as follows: ligature of the interosseous artery in one case, ligature of the radial artery in four cases, raphe of the radial artery in one case, ligature of the ulnar artery in three cases, restoration of the ulnar artery using a segment of the v. saphena in the two cases in which the Allen test had been positive. One patient died in the immediate postoperative period as a result of multiple organ failure due to polytraumatism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871312 TI - Action of the 4-nitro-2-phenoximethanesulphonanilide (nimesulide) on neutrophil chemotaxis and superoxide production. AB - 4-nitro-2-phenoximethanesulphonanilide (nimesulide) is a nonsteroidal anti inflammatory agent that has been employed in the treatment of inflammatory diseases because of its specific actions on the inflammatory response mechanisms caused by injury. The objectives of this paper were to determine the action of this agent on two notable neutrophil functions, chemotaxis and production of the superoxide anion. These two functions were studied after the neutrophils were pre incubated with three different concentrations of 4-nitro-2 phenoximethanesulphonanilide (0.1; 0.3 and 0.5 mN). The results obtained herein demonstrated that 4-nitro-2-phenoximethanesulphonanilide-exposed peripheral blood neutrophils from healthy subjects produced significantly less superoxide when challenged by phorbolmirystate acetate (PMA at 50 ng/ml) or formy-methionil leucyl-phenilalanine (FMLP 10-7 M) and opsonizided zymozan (1 mg/ml). Additionally, the agent was equally effective in reducing the PMN chemotoaxis when challenged by C5a factor (2% zimozan activated solution), FMLP 10-9 M and leukotrien (3.10-7 M). The results obtained suggest that in addition to its interference in the metabolism of the aracdonic acid, the 4-nitro-2 phenoximethanesulphonanilide may interfere in a more direct fashion with the neutrophil function. This specific action may contribute to its anti-inflammatory activity. PMID- 7871313 TI - Assessment of functional capacity during gait using a reciprocal propulsion orthosis (ARGO)--a comparative study with a conventional mechanical orthosis. AB - One subject (male, 24 years) with an incomplete motor and sensitive SCI, neurological level C6-C7 was submitted to a comparative study during gait using an advanced reciprocating gait othosis (ARGO) and a conventional mechanical orthosis (CMO) and respiratory and metabolic variables were compared at peak effort and in the second minute of recovery. We found that the ARGO, as with the CMO, not guarantee gait independence but the ARGO does enable a more functional gait pattern with a more efficient ventilation. The ratio of CO2/O2 showed that ARGO enable aerobic conditions of work and the energy expenditure using is significantly lower than CMO. PMID- 7871314 TI - Podometry: a critical evaluation of its use in Hansen's disease. AB - The aim of this paper is to evaluate the effectiveness of podometry to measure the pressure developed over the feet and the value of these findings to help in the prevention of the plantar neuropathic ulcer in patients bearing Hansen's disease. We evaluated 13 patients with impaired plantar pain and touch sensations and 17 normal patients. All the patients were submitted to static evaluation using the podometer. The system employed was the "Midcapteur" commercial podometer composed of a platform for acquisition of analogic data capable of registering the segmental pressures applied to the feet. These data are read by a 386 IBM/PC compatible computer that registers the graphic patterns obtained from the pressures developed and also calculates the modes of pressure distribution in the four quadrants of the foot. These data obtained by means of static podometry were compared to the clinical evaluation of pain and touch sensation of the feet in hansenian patients. The results demonstrate that podometery is an efficient method for evaluating the pressure in impaired feet in Hansen's disease and is a progression of neuropathic ulcer; it is sensitive in the identification of the spots of increased pressure in anesthetic and anomalous areas, asymmetries and in correlating the presence of ulcers with increased pressure. PMID- 7871315 TI - Diagnostic value of fecal leukocytes in chronic bowel diseases. AB - To evaluate the importance of fecal leukocytes, 42 patients who showed signs of fecal leukocytes (++ or +++) were studied. Their endoscopic examinations with biopsy and/or radiology of the colon showed the following diagnoses: 33 had ulcerative colitis, four had colonic adenocarcinoma, two had Crohn's disease, two had amebic colitis and one had eosinophilic colitis. The presence of fecal leukocytes allowed for the diagnosis of colon disease in all the patients, and it might indicate exudative bowel disease. These results suggest that whenever fecal leukocytes are found in the feces, an examination for colon disease should be made. PMID- 7871316 TI - Right colon volvulus associated to acquired megacolon. PMID- 7871317 TI - Donation of oocytes as treatment for infertility in patients with premature ovarian failure. Awarded the "Nicolau de Moraes Barros" prize for gynecology. AB - A total of 7 cycles of embryo transfer by oocyte donation were performed on 5 patients with premature ovary failure (POF). All donors were under 35 of age and the recipients average age was 38.6 years. For synchronization between donor and recipient a semi programmed menstrual cycle was used by means of oral contraceptive followed by ovarian stimulation of donor with clomiphene citrate and human menopausal gonadotrophin. The recipients were easily adjusted to the donors by a flexible model of gradually increasing doses of estradiol valerianate. The average number of oocytes donated was 3.14 and average embryo cleavage rate was 80.2%. The average number of embryos transferred was 2.57. Embryo implantation rate was 22.2%. Clinical gestations occurred in 57.1% of the cycles. This series is probably the first one in Brazilian literature on oocyte donation as treatment for infertility in patients with premature ovarian failure. PMID- 7871318 TI - Do estrogens improve bone mass in osteoporotic women over ten years of menopause. AB - A retrospective analysis of 24 patients with established osteoporosis and with ten or more years of menopause treated with conjugated estrogen, progesterone and calcium followed for one year has been performed. Treated women received 0.625 mg/day of conjugated estrogen from day 1 to 25, 5 mg/day of medroxiprogesterone from day 13 to 25, of each cycle, plus calcium (500-1000 mg/day), during one year (12 cycles). As control group was used 18 age-matched that received only calcium (500 a 1000 mg/day). All patients had at least two dual-photon spine and proximal femur (neck, Ward's triangle and trocanter) densities measurements performed 12 months apart. Estrogen treatment was associated with increased bone mineral density at spine and trocanter. Control group did not present any statistically change after one year in any site studied. We concluded that women with ten or more years of menopause and established osteoporosis treated with replacement hormonal therapy and calcium results in improvement of bone mineral density. These data support that women with ten or more years of menopause respond to estrogen replacement therapy with absolute increments in bone density similar to those seen in younger women, in the early menopause. PMID- 7871319 TI - Prognostic value of the histopathologic private characteristics of breast cancer in patients with no axillary lymph node involvement. AB - The biological behavior of breast cancer supports the impression that it is often a systemic disease which can recur many years after the treatment of the local lesion. Since 35% of patients without axillary nodal metastasis will have recurrence of the disease after mastectomy, prognostic indicators are necessary to identify the high-risk patients to allow a more rational adjuvant therapy. We studied the prognostic value of fatty tissue invasion, perineural involvement and lymphatic and venous peritumoral embolization in T2NOMO primary breast carcinomas. Fifty-three patients were studied after initial treatment (only Halsted mastectomy). They were divided into two groups: A (control), with 25 patients with 15 years of survival without clinical and laboratory evidence of metastasis, and group B, with 28 patients who developed metastasis after initial treatment. The results were analysed by the chi-square test (p < 0.05). The fatty tissue invasion was identified in 56.0% and 78.5% in the A and B groups respectively, while venous embolization was only detected in 8.0% of the group A tumors and in 10.7% of those in group B. Neither showed significant variation when analyzed according to the chi-square test. Lymphatic embolization and perineural involvement were found respectively in 36.0% and 40.0% in the group A tumors and in 67.8% and 71.4% of those in group B, exhibiting a significant statistical variation. When analysing the histopathological characteristics in the pre- and post-menopausal patients, the chi-square test disclosed that lymphatic embolization and perineural involvement had a significantly higher incidence only in premenopausal patients in group B. PMID- 7871320 TI - [Nutrition and pharmaco-nutrition in severe liver diseases]. PMID- 7871321 TI - [Cervical esophageal membrane and Plummer-Vinson syndrome: report of a caseload and review of the literature]. AB - Esophageal webs are an uncommon group among esophageal diseases. We report our findings in ten patients with membranes in the upper esophagus; seven of them were women. The median age was 48.5 years (range 24 to 73 years). Dysphagia was the main symptom in all patients and anemia was found in six cases. Radiologic and endoscopic studies provided the diagnosis. All patients underwent endoscopic dilatation and/or debridement and good results with this management were achieved. A review of literature of this condition and a discussion about the diagnosis, treatment and etiopathogenesis are presented. PMID- 7871323 TI - [External jugular vein as central venous access in intensive care patients]. AB - The authors studied 98 patients in need of a central venous line route, joined into two different groups: Group 1 - 62 (63.3%) patients, and Group 2 - 36 (36.7%). All the patients had a visible external jugular vein while on Trendelenburg position. According to the Seldinger technique using a J-wire guided catheter the authors describe a maneuver to make it easy to advance the catheter. Patients from Group 1 had the technique applied by operators with previous experience, and patients from Group 2 by operators with no previous experience, but under supervision. There was no significant difference in the success rate between these two groups: 96.8% in Group 1 and 94.4% in Group 2 (p > 0.5). There was only one case of local bleeding, managed by local compression. PMID- 7871322 TI - [Colonoscopy and digital cytometry in the clinical assessment of prolonged non specific ulcerative rectocolitis]. AB - Twenty-one patients having ulcerative colitis (U.C.) for a period of seven or more years, and considered as being in the risk group for developing large bowel neoplasia, were studied according to the following procedures: 1) colonoscopic examination for macroscopic identification of mucosal alterations and obtainment of multiple biopsies; 2) histologic examination of mucosal biopsies; 3) quantification of mucosal-cell DNA using digital cytometry. The duration of disease in these patients ranged from seven to 33 years, with an average of 14 years. In three patients colonoscopic images showed vegetant lesions suggestive of malignancy. The association of UC with cancer occurred in 14% of cases. Colonoscopy was efficient in providing accurate diagnosis in all cases and also allowed a successful endoscopic resection of an aneuploid neoplastic lesion. Digital cytometry revealed diploid DNA histogram in all phases of U.C. and aneuploid in cases with association of UC and neoplastic development. CONCLUSION: these three methods together should be utilized in the follow-up of patients with long standing ulcerative colitis. PMID- 7871324 TI - [Pseudotumor of the stomach: study of 10 cases and review of the literature]. AB - Pseudotumoral form of gastric ulcer is an infrequent clinical presentation of peptic disease. We present the findings in ten patients with this variety of gastric peptic ulcer treated in the last five years. All records including preoperative radiological and endoscopic examinations are reviewed. Five patients were women and five were men. The median age of patients was 62.1 years (range, 45 to 79 years). Epigastric pain was the main symptom in 90% of patients and weight loss in 70%. Six patients underwent surgical treatment. There was no perioperative mortality. A review of literature of this condition and a discussion about the differential diagnosis are presented. PMID- 7871325 TI - [Mediastinoscopy: technical aspects and current indications]. AB - Mediastinoscopy is an useful tool for mediastinal exploration with minimal surgical trauma. The anatomical and Technical basis of this procedure are simple and safe, and can be adapted to specific purposes. Surgical intervention is performed under general anesthesia and is carried out direct visual inspection. Mediastinoscopy is a diagnostic routine procedure in lung cancer staging and mediastinal adenopathy investigation. Since Carlens described the method of cervical mediastinoscopy, other authors developed new techniques, in order to improve and extend the range of mediatinal exploration. The mediastinoscope and the other tools used to perform the classic mediastinoscopy can also be used to perform pleuroscopy and even the transmediastinal esophagectomy. PMID- 7871326 TI - [Hospital bacteremia at the "Instituto do Coracao do Hospital das Clinicas da FMUSP": a four-year retrospective study]. AB - We conducted a retrospective study to establish mortality rates and prevalence of nosocomial bacteremias at our institute. We found 1.21 nosocomial bacteremias per 100 hospital discharges with an overall Mortality rate of 29.5%. Primary bacteremias increased during the four-year-study-period from 31 to 41%. Staphylococcus, both coagulase-positive and coagulase-negative, was the bacteria most frequently isolated. An abrupt increase in the isolation of P.aeruginosa occurred in 1992. We concluded that a blood-culture surveillance program is required for determining an endemic rate. PMID- 7871327 TI - [Rectal endometriosis]. AB - Colorectal endometriosis is a relatively rare entity that may have a wide array of clinical symptoms and radiographic findings. A 42-year-old female patient with rectal endometriosis treated with danazol under CA 125, CA 19-9 and estrogen monitoring is described. The treatment was successful and the patient underwent excision of reproductive organs without colorectal excision. PMID- 7871328 TI - [Poisoning caused by external use of iodoform]. AB - A case of iodoform toxicity caused by use of 5% iodoformed bandage in occlusive surgical dressings for tamponing of diffuse hemorrhage in pelvic cavity, following amputation for treatment of rectum adenocarcinoma. Despite the frequent use of iodoformed dressings following surgical procedures, the signs and symptoms of iodoform toxicity syndrome can be easily mistook for other syndromes. A revision of the published observations suggest that this syndrome is not as rare as thought but probably has been underdiagnosed. PMID- 7871329 TI - [A fatal case of lower gastrointestinal hemorrhage: report of case and review of the literature]. AB - Gastrointestinal hemorrhage continues to be a major medical problem. Even with improvements in both diagnostic and therapeutic, a significant number of patients still require surgical intervention for control of hemorrhage. When the source of persistent lower gastrointestinal hemorrhage is unknown, subtotal colectomy is a conceptually rational management choice. The authors present a case of massive lower gastrointestinal hemorrhage with unusual fatal outcome. A review of literature of this condition and a discussion about the diagnosis, treatment and etiopathogenesis are presented. PMID- 7871330 TI - [Intra-institutional operative diagnosis of medical schools]. AB - The difficulties for the establishment of operative diagnosis of a high educational institution such as a medical school are examined by the author. The importance of the implementation of the evaluation patterns of the school is stressed. A set of different evaluative parameters is indicated. They concern: teaching-learning process; teaching and administrative resources; research activities; and general administration. The procedure is exemplified by data from the Medical School of the University of Sao Paulo. PMID- 7871331 TI - Serum IgM rheumatoid factor by enzyme-linked immunosorbent assay (ELISA) delineates a subset of patients with deforming joint disease in seronegative juvenile rheumatoid arthritis. AB - Using human IgG as an antigen in an enzyme-linked immunosorbent assay (ELISA), we looked for the presence of IgM rheumatoid factor (RF) in the sera of 74 children with juvenile rheumatoid arthritis (JRA). Nine children had RF detectable by both latex agglutination and ELISA. Forty-five percent (26 of 65) of the children who were seronegative by latex agglutination were found to be positive for IgM RF by ELISA. The prevalence of IgM RF was higher in patients with polyarticular onset disease (57.4%) than in those with pauciarticular onset (38.5%) or systemic onset (27.2%) disease. The prevalence of RF was higher in sera from patients with deforming joint disease than those without deformities (P < 0.01). PMID- 7871332 TI - Effect of clodronate on established adjuvant arthritis. AB - The rat adjuvant arthritis model was used to study the effect of disodium clodronate on inflammation and destruction of tarsal bones and joints. Male Lewis rats were given an intradermal injection of mycobacteria. Fourteen days after immunization, rats with similar scores were assigned to the different experimental groups. They were treated subcutaneously either with saline (controls) or with clodronate at doses of 12.5 and 25 mg/kg/day five times a week for 2 weeks. Clinical signs of arthritis including the severity of paw swelling were assessed weekly. At the time of sacrifice, histological features of the non decalcified tarsus with ankle, intertarsal and tarsometatarsal joints were assessed for inflammatory soft-tissue, articular and bone changes. The total histological score of the hindpaw indicated that 58% of the control rats developed moderate arthritis and 42%, severe arthritis. The treatment with clodronate (25 mg/kg) decreased clinical signs of arthritis and the activity of the collagen-degrading lysosomal enzyme, beta-N-acetylglucosaminidase, in inflamed hindpaw tissue. Histological evaluation indicated moderate arthritis in 83%, but no severe arthritis. The lower dose of clodronate also decreased the severity of the disease; the decrease was, however, statistically insignificant. The results show that clodronate given therapeutically to adjuvant arthritic rats suppresses the intensity of the inflammation and prevents secondary articular and bone lesions in the tibiotarsal region. PMID- 7871333 TI - A radioreceptor assay for TNF alpha-binding proteins. AB - A radioreceptor assay for tumour necrosis factor alpha (TNF alpha)-binding proteins was development that is suitable for use with synovial fluids and sera. This assay, an alternative to the commonly used enzyme-linked immunosorbent assays (ELISAs), is not specific for soluble tumour necrosis factor alpha receptors (sTNF-R), but detects any molecules that might compete with TNF alpha for receptor binding. It also detects molecules that might bind TNF alpha and thereby interfere with subsequent binding to receptor. In a preliminary study, the assay was used to determine levels of TNF alpha-binding activity in a test group of synovial fluids from patients with rheumatoid arthritis (RA), osteoarthritis (OA) or psoriatic arthritis (PA). Levels of binding activity were much higher than those reported for sTNF-R alone in other studies [1, 2]. Our results indicated that there may be other molecules associated with the inflamed synovium that can interfere with the binding of TNF to its receptors and so attenuate its effect in diseases such as RA. PMID- 7871334 TI - Anti-neutrophil cytoplasm antibodies (ANCA) in rheumatoid arthritis: relationship to HLA-DR phenotypes, rheumatoid factor, anti-nuclear antibodies and disease severity. AB - To investigate a possible relationship between the presence of anti-neutrophil cytoplasm antibodies (ANCA), rheumatoid factors (RF), anti-nuclear antibodies (ANA), disease severity and HLA-DR phenotypes, 46 consecutive ANCA+ and 48 ANCA-, clinically well-documented RA patients were studied for RF, ANA and HLA-DR phenotypes. The 46 ANCA+ patients showed predominantly an atypical perinuclear staining pattern (89%). ANCA positivity was associated with higher RF titres (P < 0.005) and advanced functional Steinbrocker grades III/IV (P < 0.015). ANCA+ patients were also more often positive for ANA than ANCA- patients (P < 0.008). There was no correlation between ANCA positivity and certain HLA-DR phenotypes although the frequency of DR4+ (67% vs 52%) and, in particular, of DR4+ blanks (phenotypically homozygous) was increased in ANCA+ as compared to ANCA- patients (20% vs 8%). DR4-DR1-RA patients were twice as frequent in the ANCA- than in the ANCA+ group (22.9% vs 8.7%). Correspondingly, the DR4+DR1- phenotype was increased among ANCA+ RA patients. Regarding functional Steinbrocker grades, the DR4+ phenotypes were slightly but not significantly increased in grades III and IV whereas ANCA positivity was significantly associated with severe functional Steinbrocker grades III/IV (66% ANCA+ vs 39% ANCA-, P < 0.015). ANCA positivity identified a population of RA patients with a long-standing and severe clinical course of the disease. There was no correlation between ANCA positivity and certain HLA-DR phenotypes. PMID- 7871335 TI - TCR1+ large granular lymphocyte proliferation in rheumatoid arthritis. AB - The T gamma-lymphoproliferative syndrome is characterized by a proliferation of large granular lymphocytes (LGL). It is often associated with neutropenia, and in 30% of cases with rheumatoid arthritis (RA). Phenotypic analysis has demonstrated that in most cases of RA with T gamma-proliferative disease, the LGL represent T cells with a clonal rearrangement of the alpha/beta T cell receptor (TCR2). Here, three patients with gamma/delta TCR1+ LGL proliferation suffering from long standing arthritis and neutropenia are described. The first patient with RA showed an expansion of a heterogeneous CD2+ CD16+ CD56- LGL population, of which 30% coexpressed TCR1 with V delta 1 rearrangement. The second patient with ankylosing spondylitis and RA was suffering from proliferation of TCR1+ (V gamma 9-, V delta 1-), CD2+ CD16- CD56- LGL with low coexpression of CD8. The third patient with RA was suffering from a proliferation of TCR1+ (V delta 1+, V gamma 9-) CD4- CD8- CD16- CD56- lymphocytes. On the basis of these unusual findings, the pathogenetic role of TCR1+ T cells in RA is discussed. PMID- 7871337 TI - [Business/and reason: reflections for use]. PMID- 7871336 TI - Evidence for direct anti-heparin-sulphate reactivity in sera of SLE patients. AB - Recently it has been suggested that anti-ds-DNA antibodies (Abs) promote tissue damage in systemic lupus erythematosus (SLE) by cross-reactivity with highly negatively charged tissue components such as heparan sulphate (HS), the major glycosaminoglycan of the glomerular basement membrane (GBM). Other authors, however, support the theory of DNA-anti-dsDNA immune complex deposition in situ. To further elucidate the possible role of HS antibodies, we developed a new ELISA system with heparan sulphate bound to solid phase. SLE patients (n = 40) showed a higher reactivity against HS (mean = 28.4, SD = 34.3) as compared to normal donors (n = 28, mean = 15.2, SD = 6.3) and patients with rheumatoid arthritis (n = 35, mean = 14.3, SD = 6.4). The addition of native dsDNA or HS to SLE sera was followed by a dose-dependent reduction in anti-HS reactivity. In contrast, in an anti-dsDNA ELISA, no reduction was observed when HS was added to SLE sera. An increase in reactivity was observed when SLE sera with and without a prior incubation with dsDNA were digested with DNAse I or II. After the purification of serum samples by protein A sepharose under dissociative conditions, seven out of eight SLE patients showed an increase in anti-HS reactivity. No correlation of the anti-HS Abs was found with organ involvement or other serological parameters. We concluded, that there is evidence for a direct anti-HS Ab reactivity in SLE sera. A part of these antibodies seems to show low avidity anti-dsDNA cross reactivity. PMID- 7871338 TI - [Clinical and nursing epidemiology of patients with ictus]. AB - A descriptive survey on time of presentation, nursing and medical interventions, course of blood pressure and final outcome (in term of disability) of stroke patients was conducted by the nurses of neurological and medical wards of 17 hospitals. Data were collected on 293 stroke patients (63% of all the stroke patients admitted to the wards during the study period). 69% of patients arrived at the Emergency Department within 6 hours from symptoms onset. Main pharmacological treatments were antiplatelet agents and osmotic diuretics, whose efficacy (for the former for the acute phase) is under debate. 37% of plegic patients was never positioned on the affected side; 5 days after the stroke 32.1% patients were incontinent but 53.1% were catherized. By day 5, 49.5% (55) patients were able to swallow both liquids and solid foods but only 31.5% (35) were mouth fed. The mean length of hospital stay was 18.2 days. 16% (43) patients died before discharge. The disability level was measured with the Ranking scale: 45% patients presented a moderate-severe disability. This survey represents the largest descriptive survey on an italian stroke population and the first conducted by nurses. PMID- 7871339 TI - [Health status of the very old at the USSL I in Turin. Epidemiological study in the area of the USSL I in Turin]. AB - The aims of the study were: a. to describe the socioeconomic conditions of a randomized sample of over 75 years elderly of Torino USL; b. to evaluate the impact on doctors of a better knowledge of patients and c. to evaluate the feasibility and the results of a collaborative teamwork with doctors, nurses and social workers. Social workers or nurses evaluated the functional abilities of the elderly with the ADL and IADL scales, the cognitive function with the Mini Mental State and depressive symptoms with the Care Scale. 40 General Practitioners were randomized in two groups and each randomly selected 5 men and 5 women over 75 years, among their patients. Half of the doctors (experimental group) were offered a WHO textbook on drug prescription for the elderly and three monthly meetings with nurses and social workers, to globally evaluate the patients situation and define necessary interventions. 340 patients were recruited for the study (mean age 81 years). No differences were observed in the outcomes of the experimental and control group. An overall improvement of diagnostic skills and reduction of drug prescription was observed in both groups, but the impact of the latter was larger in the experimental group. PMID- 7871340 TI - [Teaching research methods and statistics in the nursing school. Second part]. PMID- 7871341 TI - [Methods and instruments of nursing research: analysis of various articles]. AB - Research papers published on some of the most well known medical and nursing journals are presented and discussed. The main aim of the contribution, which opens a new arena for discussion on the Rivista dell'Infermiere is to critically appraise published research works focusing both on strenghts and novelty as well as weaknesses in the hypothesis formulation, methods and instruments used, discussion of results. A critical analysis should enable nurses to start to learn to read and eventually write a research protocol, possibly avoiding some common mistakes. PMID- 7871342 TI - [What is new in drug therapy? 1992-1994. Part 3]. PMID- 7871343 TI - [Women of the occupied territories]. PMID- 7871345 TI - [Prevention of osteoporosis]. PMID- 7871344 TI - [Assistance for immigrants: NAGA]. PMID- 7871346 TI - [What do we know about nutrition? A study done in Huelva]. PMID- 7871347 TI - [Problems in the rehabilitation and reintegration in mental disorders. Consensus on the causes]. PMID- 7871348 TI - [Therapeutic guide for physically active diabetics]. PMID- 7871349 TI - [Why does the nursing process not always work?]. PMID- 7871350 TI - [Continent systems for colostomy. II. The obturator]. PMID- 7871351 TI - [How and by what is respiration regulated? Respiratory centers]. PMID- 7871352 TI - Influence of acid-etched splinting methods on discoloration of dental enamel in four media: an in vitro study. AB - The aim of this in vitro study was to assess the staining of enamel in relation to fixation of luxated teeth. Color changes induced by chlorhexidine, red wine, tea, and coffee were detected with a Minolta Chroma Meter (CR-121) after extracted teeth were treated to simulate construction of dental splinting. L*a*b* color readings were made before and after 7 days of incubation in the above mentioned media in teeth treated 1) by acid-etching, 2) by acid-etching followed by resin, 3) by resin and composite, 4) by Triad Gel, and 5) by Protemp. L* is an indicator of black (0) and white (100). The a* values relate to the red (+100) green (-100) color axes, and the b* values to the yellow (+100) and blue (-100) axes. Untreated teeth served as controls. One-way analysis of variance of mean L* values revealed no statistically significant differences in treatment. Discoloration was observed in all teeth, including the control ones. However, Protemp yielded the largest changes in mean L* values. Analysis of variance of mean L* values revealed statistically significant differences between incubation liquids because no increase in staining of enamel was noted after 7 days' incubation in chlorhexidine. Red wine increased the mean L* values more than coffee or tea. Changes in a*b* readings were toward red (+a*) after incubation in red wine, except in the case of teeth treated with resin. The color of all such teeth changed more toward yellow (+b*), because the resin used was yellow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871353 TI - Salivary lactobacilli explain dental caries better than salivary mutants streptococci in 4-5-year-old children. AB - The present comparative study was undertaken to determine which of the bacteria, lactobacilli (lbc) and mutans streptococci (ms), in saliva better explains the variation of caries in 2728 South African 4-5-yr-old children. Caries was diagnosed according to WHO criteria. For lbc, the Dentocult system was used. The number of ms in stimulated saliva was counted on MSB agar plates. For correction of confounding factors, data on the frequency of intake of sweets were derived from extensive interviews. Oral hygiene was determined according to the simplified debris index of Greene & Vermillion. Simple correlation analyses between dmfs and bacterial counts were done for the total material and for three caries intervals by calculating Spearman's and Pearson's coefficients of correlation. Multivariate regression analyses were done on all intervals to correct for the confounding effects of regular intake of sweets, presence of salivary ms or lbc, and oral hygiene. Of the children, 68% had detectable lbc in the saliva, and 74% had ms. Except for children with more than 6 dmfs, the explanatory values, i.e., percentage of variation in dmfs explained, were higher for the lbc than for ms. Before correction, the values for the total material were 15 vs 6%; for children with caries, 7 vs 5%; for those with 1-6 dmfs, 5 vs 0.4%; and for those with more than 6 dmfs, 0.3 vs 2%. All r-values were reduced after correction, indicating that the confounders explain some of the correlation between dmfs and bacterial count.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871354 TI - Effect of buccal administration of a lactose-containing nitroglycerin tablet (Suscard) on plaque pH. AB - The aim of this study was to monitor pH in 2-day-old dental plaque after administration of a long-acting, lactose-containing nitroglycerin tablet (Suscard). The tablet was placed under the lip of the maxilla. This was done both in two older subjects suffering from heart problems and in 10 younger, healthy subjects. In the latter group, a sucrose-containing lozenge was used as a control. The influence of a 5-wk period of daily use of Suscard (in the two elderly subjects) and the effect of normal oral hygiene procedures (in the 10 younger subjects) on the pH response was also studied. Plaque pH was measured in situ up to 1 h, at five different approximal sites in the front region of the maxilla by the micro-touch method. The Suscard tablet resulted in a fall in plaque pH in both groups when teeth had not been brushed for 2 days. The lowest pH was recorded at the sites close to where the tablet had been placed. The most attenuated pH drop was found in the two older subjects, who showed a mean minimum pH of 5.7, as compared with 6.2 for the younger subjects. No further increase in the pH fall from Suscard was seen after the 5-wk period in the two patients with heart problems. In the 10 younger healthy subjects, the most pronounced pH decrease was registered after administration of the sucrose-containing lozenge. The pH drop for Suscard was not significant when normal oral hygiene procedures preceded the test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871355 TI - Defluoridation of drinking water with pottery: effect of firing temperature. AB - Excessive fluoride (F) in drinking water should be removed, but simple, inexpensive methods of fluoride removal are not readily available. This study examines the F(-)-binding capacity of clay and clayware, especially the effect of the firing temperature on the F(-)-binding process. A series of pots were made from ordinary potter's clay and fired at 500-1000 degrees C. Likewise, small clay bricks were fired and then crushed and sieved. NaF solutions containing 10 mg/l F (10 ppm F-) were prepared. Suitable aliquots of the solutions were poured into clay pots or exposed to powdered clayware. Samples were taken at storage periods of 30 min to 20 days and analyzed for F- by ion-selective electrodes. The rate and capacity of F(-)-binding in the clayware varied with the firing temperature. Clay fired at approximately 600 degrees C was most effective. Temperatures over 700 degrees C caused a decline in F(-)-binding, and pottery fired at 900 degrees C and above seemed unable to remove F- from water. Pots fired at 500 degrees C or less cracked in water. The findings indicate that clayware, fired at an optimal temperature, may be of practical value for partial defluoridation of drinking water. PMID- 7871356 TI - The plasminogen-activating system in gingival fluid from adults. An intra individual study before and after treatment of gingivitis. AB - High concentrations of tissue plasminogen activator (t-PA) and placental type plasminogen activator inhibitor (PAI-2) have previously been found in gingival crevicular fluid (GCF) of adults and children. In the present study, intra individual comparisons were made of the concentrations of t-PA, urokinase type plasminogen activator (u-PA), PAI-1, and PAI-2 in GCF from the same sites before and after periodontal treatment in eight healthy male volunteers aged 35-46 yr. The gingival state was assessed by exudate measurement, bleeding on standardized probing, and the gingival index of Loe & Silness 3 days before the start of the trial and on the day after completing a 21-day preventive program consisting of instruction and professional cleaning once a week. Eight sites per subject were selected for enzyme analyses, all showing improvement in gingival state during the period. Sampling of GCF at the start and at the end of the trial was done with small disks of Millipore-filter. t-PA and PAI-2 were analyzed with enzyme linked immunosorbent assays with low method errors. The mean concentrations of t PA were 0.73 mg/l before treatment and 0.49 mg/l after treatment. The mean concentrations of u-PA were 84.4 micrograms/l before treatment and 101.6 micrograms/l after treatment. PAI-1 was found in three subjects at the detection level. The mean PAI-2 concentrations were 2.19 mg/l before and 1.13 mg/l after treatment. The mean molar ratio PAs/PAI-2 was 0.47 before and 0.48 after treatment. This insignificant change implies a maintained proteolytic balance and indicates that PAI-2 is an important inhibitor of tissue proteolysis. PMID- 7871357 TI - Immunohistochemical study of neutrophil- and fibroblast-type collagenases and stromelysin-1 in adult periodontitis. AB - Eight adult periodontitis (AP) patients were studied immunohistochemically to determine the presence of matrix metalloproteinases (MMPs) MMP-1, MMP-3, and MMP 8 in the marginal gingival and gingival granulation tissue specimens obtained from periodontal flap surgery after scaling and root planing. Clinically healthy gingival tissue specimens obtained from impacted third-molar extraction operations served as controls. MMP-type-specific antisera were applied by the avidin-biotin-peroxidase complex staining method. Moderate immunoreactivity for neutrophil collagenase (MMP-8) was found both in the AP patients' marginal gingival connective tissue and in gingival granulation tissue specimens. Immunoreactivity for fibroblast-type collagenase (MMP-1) and stromelysin-1 (MMP 3) was detected only in the AP patients' gingival granulation tissue specimens. In the control specimens, no immunoreactivity for the MMPs could be detected. For the first time, this finding demonstrates immunohistochemically the presence of MMP-8 in human inflamed gingiva in situ, and further highlights the importance of MMP-8 in periodontal tissue destruction, evidently during the acute phase(s) of the disease. However, our results confirm and extend previous studies indicating that other types of MMPs from resident gingival cell sources also seem to participate in the chronic and destructive course of periodontal inflammation. PMID- 7871358 TI - Change from mixed diet to lactovegetarian diet: influence on IgA levels in blood and saliva. AB - IgA concentrations in human plasma, and whole and parotid saliva were measured before and 3 months after a shift to a lactovegetarian diet in 20 volunteers (four men and 16 women mean age 44 yr, range 27-61). The major dietary trends observed were an increased intake of berries and other fruits, vegetables, and dairy products, and a decreased intake of fish, eggs, and meat; biscuits and buns; sweets; alcoholic beverages; coffee; and tea. The consumption of meat, fish, and eggs decreased to zero, showing that the participants had adopted a lacto-vegetarian diet. There was a decrease in fat, protein, sucrose, and alcohol intake and an increase in total carbohydrate and fiber intake. There was no significant change in energy, retinol equivalent, or zinc intake. Despite this change in diet, no significant changes were observed between the mixed diet period and the vegetarian diet period in IgA in plasma, 253 +/- 52 and 264 +/- 55; whole saliva, 2.5 +/- 0.4 and 2.4 +/- 0.4; or parotid saliva, 0.88 +/- 0.22 and 0.90 +/- 0.20 (mg/100 ml, mean values, 95% confidence interval). Moreover, the diet change did not alter the secretion rate in whole and parotid saliva, the secretion rate of IgA in whole and parotid saliva, or the protein content of whole saliva. However, the protein content of parotid saliva increased significantly. Thus, this major diet change was apparently not drastic enough or sustained long enough to cause a change in IgA levels. PMID- 7871359 TI - Microbiologic tests in epidemiologic studies: are they reproducible? AB - Microbiologic assessments are often included in longitudinal studies to elucidate the significance of the association of certain Gram-negative bacteria and the development of periodontal diseases. In such studies, the reliability of methods is crucial. There are several methods to identify putative pathogens, and some of them are commercially available. The purpose of the present study was to compare the reproducibility of four different methods for detecting Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia in order to evaluate their usefulness in epidemiologic studies. The test panel consisted of 10 young subjects and 10 adult periodontitis patients. Subgingival plaque was sampled from sites showing bone loss and "healthy" control sites. The four different methods for detecting the target bacteria were 1) cultivation, 2) Evalusite (a chair-side kit based on ELISA), 3) OmniGene, Inc, based on DNA probes, and 4) indirect immunofluorescence (IIF). The test procedure was repeated after a 1-wk interval and was performed by one examiner. Sites reported to be positive for a microorganism by any of the four methods at one or both examinations were considered to be positive for that organism and included in the analysis. The reproducibility of the four methods was low. The IIF and the cultivation methods showed somewhat higher reproducibility than did the commercial systems. A second test was done for Evalusite, three paper points for sampling being used instead of one as described in the manual. The reproducibility of the second test was improved, indicating that the detection level of the system may influence the reliability. PMID- 7871360 TI - Miconazole lacquer compared with gel in treatment of denture stomatitis. AB - An open, randomized, controlled study with two parallel treatment groups was done to evaluate the efficacy and safety of a single application of a miconazole 55 mg/g denture lacquer applied once on the mucosal denture surface, as compared with those of a commercially available miconazole 2% gel applied four times daily for 2 wk, in the treatment of Candida-associated denture stomatitis. The efficacy variables were Candida cultures on the Oricult plates taken from the palatal mucosa and the denture surface, erythema of the palatal mucosa, and smears for leukocyte migration into the palatal epithelium taken on entering the study and on days 3, 7, 14, 21, 28, and 35 after commencement of therapy. On entering the study, all patients had positive cultures of yeast in the samples from the palatal mucosa. Within the first 3 days, all gel patients and 88% of the lacquer patients had fewer than 10 colonies. The gel was statistically significantly more efficient than the lacquer on days 7 and 14. In the samples from the denture surface, all patients had more than 100 yeast colonies at inclusion and, on day 3, approximately 80% in both treatment groups had fewer than 10 colonies. From day 7 onward, the gel was statistically significantly more efficient than the lacquer. The reddening of the palatal mucosa was not statistically significantly different in the treatment groups at any of the examinations, but smears for the determination of leukocyte migration indicated that the gel was statistically significantly more efficient than the lacquer on day 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871361 TI - Dental injuries, temporomandibular disorders, and caries in wrestlers. AB - The aim of this study was to examine the prevalence of dental injuries, temporomandibular disorders (TMD), and dental caries in a group of champion wrestlers. Twenty-six male wrestlers, with a mean age of 23 yr, and an age matched control group participated in the study. A questionnaire was used with questions on trauma, frequency of headache, intensity of practicing sports, use of sugar-containing "sports drinks", use of mouth guards, and previous TMD problems. Four bitewing radiographs were taken in all subjects. In addition, three intraoral apical radiographs of maxillary and mandibular frontal regions were taken in the wrestlers. The number of existing teeth, dental caries, amount and type of restorations, and dental injuries were recorded. Examination of the stomatognathic system comprised bilateral palpation of the masseter and temporal muscles and temporomandibular joints, and evaluation of the mandibular movements. None of the subjects had drunk sports drinks or worn mouth protectors regularly. The wrestlers had more frequent and severe dental injuries localized to the frontal region of the maxilla than the controls. No statistical differences were found in the prevalence of caries or TMD between the groups. PMID- 7871362 TI - Bite force on single as opposed to all maxillary front teeth. AB - The relation of number of teeth to maximal clenching force was tested in 10 healthy female dental students. The maximal force in the interincisal position was tested by spreading the load with individual acrylic splints over a varying number of teeth in the anterior region. In the maxilla, one splint covered teeth 13-23; another covered tooth 11. In the mandible, one splint covered teeth 33-43 in all experiments. The maximal force in the incisal position was measured 10 times, five times with each splint. The maxillary splints were changed in random order. The tactile sensibility of tooth 11 and its antagonists was tested before and immediately after interincisal force measurements. A highly significant difference between maximal forces was seen in comparing biting between a single tooth and multiple teeth. In addition, bite force also showed a significant increase in both single tooth and multiple teeth successive biting trials during the experiments. Tactile sensibility between d 11 and its antagonist was not altered by the maximal bite force trials. PMID- 7871363 TI - Systemically induced contact dermatitis from dental rosin. AB - Rosin is a ubiquitous contact sensitizer which may be present in dental materials such as periodontal dressings, impression materials, cements, and cavity varnishes When a hypersensitive person is exposed to a sensitizer, allergic contact dermatitis/stomatitis may develop, most commonly after direct skin/mucosa contact with the sensitizer. However, widespread dermatitis may develop after systemic administration of the sensitizer, and this paper reports the case of a rosin-hypersensitive man who developed widespread eczematous dermatitis after dental treatment with a rosin-containing product. PMID- 7871364 TI - XXIV Nordic Congress in Clinical Chemistry. Stockholm, 8-12 August 1994. Abstracts. PMID- 7871365 TI - Increased intestinal marker absorption due to regional permeability changes and decreased intestinal transit during sepsis in the rat. AB - BACKGROUND: The intestinal barrier properties are impaired during inflammation and sepsis, but the mechanisms behind this are unknown and were therefore investigated during experimental sepsis in rats. METHODS: The different-sized intestinal absorption markers 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and ovalbumin were gavaged to rats made septic by intra-abdominal bacterial implantation and to sham-operated rats. Regional tissue permeability was measured in diffusion chambers, and intestinal transit was evaluated by intestinal accumulation of gavaged 51Cr-EDTA. RESULTS: In comparison with the sham-operated rats, septic rats had higher 51Cr-EDTA levels in blood and urine and showed a prolonged intestinal transit. Septic rats also had a lower tissue permeability to both markers in the small intestines but higher permeability to ovalbumin in the colon. Rats receiving morphine to decrease intestinal motility showed similar changes, with a decreased intestinal transit and increased marker absorption. CONCLUSIONS: The results suggest that the increased intestinal absorption during sepsis was due to regional permeability changes and prolonged intestinal transit. PMID- 7871366 TI - Absorption of short-chain fatty acids from the in-situ-perfused caecum and colon of the guinea pig. AB - BACKGROUND: Short-chain fatty acids (SCFA) originate from microbial fermentation of carbohydrates in the hindgut. Mechanisms involved in SCFA absorption are not fully understood. METHODS: The caecum and proximal and distal colon of the guinea pig were perfused in situ. RESULTS: SCFA absorption per gram mucosal dry weight was highest in the proximal colon and lowest in the caecum. Owing to the large surface, quantitatively SCFA absorption was highest from the caecum. In the distal colon clearance of SCFA increased with chain length (Ac < Pr < Bu); in the caecum and proximal colon only a comparatively small or no such influence was observed. Inhibition of the proton antiport systems in the apical membrane and inhibition of the carbonic anhydrase activity diminished SCFA absorption. The diffusive and carrier components of absorption were calculated for propionate at increasing propionate concentrations. CONCLUSIONS: Marked segmental differences in SCFA absorption are apparent in the large intestine of the guinea pig. PMID- 7871367 TI - Ileostomy output and bile acid excretion after intraduodenal administration of oleic acid. AB - BACKGROUND: Ileostomy output and small-intestinal transport are regulated by complex mechanisms, which the present study aimed to further elucidate. METHODS: The time-related ileostomy output and bile acid excretion after intraduodenal administration of a fat solution (oleic acid, 3.5 g) was studied in 29 ileostomy patients. Eighteen patients had the entire small bowel preserved (group I), whereas 11 had various lengths of the ileum resected or bypassed (group II). RESULTS: Intraduodenal fat administration resulted in a prompt and significant increase in ileostomy output in both groups. The accumulated 2-h output after fat administration amounted to 60% of the normal 24-h output in group I and 30% in group II. A marked increase in bile acid excretion preceded the flow response. The fat-induced response was abolished by administration of cholestyramine. CONCLUSIONS: Bile acids seem to have important regulatory effects with regard to secretion/absorption and transport of small-bowel contents, affecting ileostomy output, with clinical implications in many patients. PMID- 7871368 TI - Radical surgery (R2 resection) for gastric cancer. A multivariate analysis. AB - BACKGROUND: Extended lymphadenectomy remains controversial in the Western world. Its evaluation and the identification of high-risk patients after surgery are important tasks. METHODS: A retrospective prognostic study of 318 patients treated for potential cure of gastric cancer was performed. All patients underwent extended lymphadenectomy. Clinical histopathologic and surgical factors were examined for their influence on survival by univariate and multivariate analysis. RESULTS: Postoperative mortality was 4.4% (14 of 318), and the 5-year adjusted survival rate was 57.8%. Multivariate analysis using the Cox model identified seven factors as having independent influence on survival. Detrimental factors were male gender, age over 65 years, high pN category, increasing number of lymph nodes invaded by metastases, total gastric resection, splenectomy, and increasing number of perioperatively required blood units. CONCLUSION: Extended lymphadenectomy was possible without sacrificing low postoperative mortality rates. The importance of certain prognostic factors, in particular lymph node status, could be confirmed. PMID- 7871369 TI - Argyrophilic nucleolar organizer regions may help the differential diagnostic distinction between chronic pancreatitis and pancreatic ductal adenocarcinoma. AB - BACKGROUND: The aim of this study was to determine whether the number of argyrophilic nucleolar organizer regions (AgNORs) could be of diagnostic significance in differentiating between chronic pancreatitis and pancreatic ductal adenocarcinoma. METHODS: The number of AgNORs was enumerated in biopsy specimens of normal pancreas, chronic pancreatitis, and pancreatic ductal adenocarcinoma. RESULTS: The number of AgNORs was lower in patients with normal pancreas than in patients with chronic pancreatitis or pancreatic adenocarcinoma. In addition, the number of AgNORs was significantly lower in chronic pancreatitis than in pancreatic ductal adenocarcinoma (p < 0.001). CONCLUSIONS: The diagnosis of pancreatic adenocarcinoma is usually clear. Difficulties can be encountered, however, in cases of chronic pancreatitis, specially when biopsy material is small. Our results suggest that the number of AgNORs may help in distinguishing between chronic pancreatitis and pancreatic ductal adenocarcinoma, especially in diagnostically difficult specimens. PMID- 7871370 TI - Effect of glutathione administration on hepatic biliary and plasmatic glutathione levels in the rat. AB - BACKGROUND: Since the effect of exogenous glutathione (GSH) on overall hepatic GSH homeostasis is not known, the present study investigated the changes in the hepatic, biliary, and plasmatic GSH levels during GSH administration in intact rats. METHODS: An exteriorized biliary-duodenal fistula was established, and GSH (1 mmol/kg over 2 h) or saline was administered intraperitoneally to rats with or without pretreatment with 5 mmol/kg L-serine borate, an inhibitor of gamma glutamyltransferase (GGT). RESULTS: Three hours after GSH administration, biliary GSH efflux and bile flow rose from 104.7 +/- 5.6 to 290.6 +/- 8.6 micrograms/ml bile and from 20.2 +/- 1.3 to 30.2 +/- 2.1 microliters/min, respectively; GSH treated rats also showed increased liver (35%) and posthepatic vein plasma (68%) GSH concentrations compared with controls. By contrast, in rats pretreated with the GGT inhibitor GSH administration appeared to be devoid of any effect, except for a modest biliary GSH increase. CONCLUSIONS: This study indicates that significant changes occur in the hepatic GSH homeostasis after intraperitoneal GSH administration. The activity of hepatic GGT, most likely through degradation of circulating GSH, followed by an increase in cysteine availability, seems to account, at least partially, for the reported effects. PMID- 7871371 TI - Efficacy of interferon therapy in patients with chronic hepatitis C. Comparison between non-drinkers and drinkers. AB - BACKGROUND: Alcohol has been reported to be an important factor that modulates the development and prognosis of chronic viral hepatitis; however, little is known about interaction of alcohol intake and chronic hepatitis C. The aim of this study was to examine whether alcohol drinking affects the effectiveness of interferon (IFN) therapy for chronic hepatitis C. METHODS: Thirty-nine patients with chronic hepatitis C were divided into three groups on the basis of the amount of alcohol intake before IFN therapy: group I (n = 15), non-drinkers; group II (n = 14), less than 70 g/day; and group III (n = 10), more than 70 g/day of ethanol intake for at least 10 years. The IFN (total dose, 330 +/- 206 MU) was administered daily for 2 weeks and then intermittently. Drinkers stayed abstinent for at least 1 month before, during, and after IFN therapy. The sustained responder was defined as the patient who showed normal alanine aminotransferase (ALAT) levels continuously for more than 6 months after the therapy. The liver histology (HAI score) and serum hepatitis C virus (HCV) RNA were also examined before and after the therapy. RESULTS: There was no significant difference among the three groups in the level of ALAT before IFN therapy, age, total dose of IFN, and liver histology. The rates of sustained responders in groups I, II, and III were 53.3%, 42.9%, and 0%, respectively, resulting in a significantly lower rate in group III than in groups I (p < 0.01) and II (p < 0.01). The serum HCV-RNA turned negative after the therapy in 58.3%, 20.0%, and 12.5% of groups I, II, and III, respectively, leading to a significantly lower rate of disappearance of HCV RNA in group III than in group I (p < 0.05). CONCLUSION: The IFN therapy for chronic hepatitis C was less effective in heavy drinkers than in non-drinkers. PMID- 7871372 TI - Effects of dobutamine on hepatosplanchnic hemodynamics in patients with chronic liver disease. AB - BACKGROUND: It is said that catecholamines increase hepatic blood flow in patients without liver diseases, although several reports have suggested a blunted response to catecholamines in patients with liver cirrhosis. METHODS: We investigated changes in splanchnic blood flow distribution induced by the infusion of dobutamine into peripheral veins of healthy adults (NC group), patients with chronic hepatitis (CH group), and patients with liver cirrhosis (LC group), using a Doppler duplex system (protocol 1). We also investigated changes in hepatic hemodynamics induced by dobutamine infusion in patients with liver cirrhosis (cirrhosis group) and patients without liver diseases (control group), using hepatic catheterization (protocol 2). RESULTS: In protocol 1 the average increase in portal venous blood flow during dobutamine infusion was significant in the NC and CH groups but was not significant in the LC group. Changes in the blood flow in the splenic artery and vein, superior mesenteric artery and vein, and femoral artery were similar to those in the portal vein in each of the three groups. Infusion did not cause a change in the common hepatic arterial flow in any of the three groups. In protocol 2 the portal venous flow, cardiac index, and hepatic venous pressure gradient increased significantly during dobutamine infusion in both the cirrhosis and the control groups. Hepatic vascular resistance in the cirrhosis group increased slightly, whereas, in contrast, that in the control group increased significantly. The rate of change in almost all variables was lower in the cirrhosis group than in the control group. CONCLUSION: These results indicate that dobutamine has less effect on hepatic circulation in patients with liver cirrhosis than in those without liver diseases, indicating that the value of dobutamine in increasing hepatic blood flow in cirrhotic patients is very limited. PMID- 7871373 TI - The novel anti-ulcer agent ecabet sodium (TA-2711) eradicates Helicobacter pylori colonizing on the gastric mucosa of Japanese monkeys. PMID- 7871374 TI - Positive correlation between H,K-adenosine triphosphatase autoantibodies and Helicobacter pylori antibodies in patients with pernicious anemia. AB - BACKGROUND: Helicobacter pylori is a major cause of gastritis, and the parietal cell H,K-adenosine triphosphatase (ATPase) is a major autoantigen in autoimmune atrophic corpus gastritis, which may eventually lead to pernicious anemia and/or neuropathy. Whether the bacterium induces the autoimmune response is unknown. METHODS: By means of enzyme-linked immunosorbent assay the occurrence of antibodies against porcine H,K-ATPase and H. pylori was determined in sera from 30 patients with pernicious anemia. RESULTS: All sera scored positive against H,K ATPase, and 25 (83%) scored positive against H. pylori. The titers of antibodies against both antigen preparations inversely correlated with the duration of disease. A possible common epitope in the antigen preparations was tested with a competition assay. There was no indication of a common epitope in either human or porcine H,K-ATPase and H. pylori. CONCLUSIONS: There was a positive correlation and a high incidence of antibodies against H,K-ATPase and H. pylori in sera from patients with pernicious anemia. These antibodies recognized different epitopes. PMID- 7871375 TI - Do infiltrating leukocytes contribute to the adaptation of human gastric mucosa to continued aspirin administration? AB - BACKGROUND: Aspirin (ASA)-induced gastropathy decreases with continued ASA ingestion due to the development of gastric mucosal tolerance. However, the mechanism of the gastric mucosal adaptation to repeated ASA challenge is unknown. METHODS: The aim of the present study was to determine the density of leukocytes infiltrating the gastric mucosa in healthy subjects during prolonged treatment with ASA. In eight healthy volunteers ASA treatment (2 g/day) was continued for 14 days. Endoscopy was performed before medication, on the 3rd, 7th, and 14th day of ASA treatment, and on the 16th and 18th day (2 and 4 days after medication was stopped). Gastric damage was scored (Lanza score), and gastric biopsy specimens were taken from both the oxyntic and antral mucosa. RESULTS: ASA administration resulted in the development of hemorrhagic erosions, which were most severe on the 3rd day of the medication; later significant reduction of severity of the damage was observed. ASA administration caused an increased mucosal infiltration of leukocytes; leukocyte margination and adherence to endothelia were commonly observed in the gastric mucosa, particularly on the 3rd day of ASA treatment but not later on. Mast cell density increased significantly on the 3rd day of ASA treatment. Density of mast cells later decreased in the antral mucosa but continued to be significantly increased in the oxyntic mucosa up to the 14th day. There was a striking correspondence between mast cell density and endoscopic score of the mucosal damage. Eosinophil density increased significantly during ASA treatment and remained high even after medication was withdrawn. CONCLUSIONS: 1) Initial mucosal damage by ASA is followed by gastric adaptation on continuous exposure to this agent; 2) infiltrating leukocytes appear to contribute to the development of gastric mucosal adaptation to ASA; and 3) mast cell density reflects the endoscopic score of gastric damage by ASA. PMID- 7871376 TI - Assessment of gastric acid output by H2 breath test. AB - BACKGROUND: The standard method to measure gastric acid secretion is the aspiration of gastric juice. A noninvasive breath test after application of magnesium has been proposed. The aim of this study was to modify the method, to possibly improve the discriminatory value of the test in comparison with intubation tests. METHODS: We measured the time course of the reaction of magnesium and gastric acid in vitro and determined the gastric hydrogen kinetics in humans by insufflation of hydrogen into the stomach and measuring its reappearance in the exhaled air. Thereafter, a comparison of the breath test and the intubation test was done in 10 healthy volunteers in different secretory states. RESULTS: After hydrogen insufflation 31.4% reappeared in 90 min (16.3% exhaled, rest belched). Discriminant analysis showed that the intubation test had a good discriminatory power. On the other hand, the breath test failed to distinguish between different secretory states (stimulation, inhibition, and intermediate). CONCLUSION: Whereas the intubation test discriminated between high and low acid secretion, the breath test did not. This test therefore seems, at least as performed here, unsuitable as a diagnostic test of gastric acid secretion. PMID- 7871378 TI - Late outcome of bleeding gastric ulcer. Five to eight years' follow-up. AB - BACKGROUND: Gastric ulcer haemorrhage is associated with a high immediate mortality, but few data exist on the late prognosis of these patients. The aim of this study was to determine the long-term recurrence rate and late outcome in patients with gastric ulcer complicated with bleeding. METHODS: In a prospective follow-up study 90 consecutive patients with a bleeding gastric ulcer discharged after non-operative treatment (bleeding controlled by endoscopic electrocoagulation or ceased spontaneously) were followed up once every year for 5-8 years (median, 6.5 years). RESULTS: Recurrent ulcer was seen in 17 patients, repeat haemorrhage being the presenting symptom in 13 of them. The estimated cumulative recurrence rate after 2, 5, and 8 years was 10%, 19% and 33%, respectively. Recurrence rate was unaffected by sex, complicating disease, and non-steroidal anti-inflammatory drugs (NSAIDs) ingestion before and after the index bleeding episode. The recurrence rate of patients with a history of ulcer before the index bleeding episode did not differ from that of patients with no previous ulcer history. A significantly increased risk of recurrence was seen in patients with previous bleed as opposed to patients with previous non-bleeding ulcer (p < 0.05). The cumulative survival rate was significantly reduced compared with the expected survival rate of the sex- and age-matched background population (p < 0.01), primarily because of diseases not related to the ulcer disease. CONCLUSION: Bleeding gastric ulcer is associated with a relatively low long-term recurrence rate, except in a few patients with a history of previous bleeding ulcer, who have an increased risk of recurrence. Patients with bleeding gastric ulcer have an excess mortality not related to the ulcer disease. PMID- 7871377 TI - On the natural history of peptic ulcer. AB - BACKGROUND: Three out of 1000 individuals have peptic ulcer every year, and 20% of the ulcer episodes are associated with bleeding. Whether major innovations such as endoscopy and strong acid-suppressing drugs have had any impact on the natural course of peptic ulcer disease is largely unknown. METHODS: Three hundred and fifty-one patients (median age, 63 years) with endoscopically proven peptic ulcer during 1979-1984 were included in the study and retrospectively followed up via medical records. The total population is based on two different groups of patients, the first comprising 229 consecutively diagnosed ulcer patients during 1979-81 and, to increase the number of bleeders, a second group including 122 bleeding ulcer patients consecutively diagnosed during 1981-84. At the end of the follow-up period all non-ulcer-operated patients were asked to answer a questionnaire on symptoms, investigations, and medication. RESULTS: The male to female ratio was 2.4:1 in duodenal ulcer patients, but a 1:1 ratio was shown both in gastric and prepyloric/pyloric ulcer patients (p < 0.001). Patients with bleeding ulcers were significantly older than non-bleeders (68 years versus 58 years; p < 0001), as were patients with gastric ulcers compared with prepyloric/pyloric or duodenal ulcer patients (68 years versus 63 and 61 years, respectively; p < 0.01). The 10-year cumulative mortality in the unselected group (median age, 62 years) was 43%, and the annual risk of dying of peptic ulcer disease was 0.6%. No difference in 10-year recurrence rate was seen between patients with bleeding ulcer at inclusion and non-bleeders (46.2% versus 44.3%; p = NS), but the annual risk of bleeding was 5.3% and 0.8%, respectively (p < 0.0001). In the group of patients answering the questionnaire 51% reported upper abdominal pain during the last year of follow-up. CONCLUSIONS: In spite of today's treatment regimens almost half of the patients with peptic ulcer disease experienced recurrence during a 10-year period, and more than half had ulcer symptoms after 10 years. Most probably, maintenance treatment with H2-receptor antagonists should have been offered more liberally during the 1980s. PMID- 7871379 TI - Survey of prescriptions for peptic ulcer drugs (ACT class AOB2) in Iceland. AB - BACKGROUND: The consumption of peptic ulcer drugs in Iceland is 20 DDD/1000/day, which is two to three times higher than in other Scandinavian countries. This study was done to register the pattern of use and possibly to find reasons for the high consumption. METHODS: Prescriptions for peptic ulcer drugs (ACT class AO2B) were surveyed in Iceland during 1 month in 1991. All pharmacies in Iceland participated in the study, and information was obtained on about 90% of peptic ulcer drugs used outside hospitals. The pharmacists registered all prescriptions of peptic ulcer drugs with regard to the age and sex of the patient, speciality of the prescribing physician, and name, dose, and quantity of the drug. RESULTS: A total of 2021 prescriptions were registered, accounting for 15.4 DDD/1000/day. The prevalence of peptic ulcer drug use was 1.52%, but female use was 52.5%. The maximal use, 2.91% was in the age group 70-79 years. H2 blockers accounted for 79%, omeprazole for 17%, and other drugs for 4%. General practitioners prescribed 65% of the drugs, gastroenterologists 15%, and other specialists 14%. If the patient himself collected the drug, he was asked to fill out a questionnaire with regard to the reason for the prescription, previous prescriptions, and investigations. A total of 1131 (56%) of patient questionnaires were received. Only 1% of the patients did not know the reason for the prescription. The patients registered that 30% of the prescriptions were for peptic ulcer, 29% for heartburn, 21% for gastritis, 9% for dyspepsia, and 7% for prevention of side effects of other drugs. It was estimated from the data that about 40% of the prescriptions were for non-ulcer dyspepsia. Investigations were done in 67% of the patients, but 33% received the prescription only after an appointment with a physician. CONCLUSIONS: The results of the survey suggest that the extensive use of peptic ulcer drugs in Iceland is mostly due to excessive use in non-ulcer dyspepsia. PMID- 7871381 TI - Reduced IL-2 expression upon antigen stimulation is accompanied by deficient IL-9 gene expression in T cells of patients with CVID. AB - Patients with common variable immunodeficiency (CVID) are heterogeneous in the clinical manifestation of the disease as well as in the underlying mechanisms leading to the immunodeficiency. In a previous study we identified a subgroup of patients with a primary immunodeficiency disease affecting IL-2 and IFN-gamma gene expression. The T cells of these patients revealed impaired proliferative response and reduced levels of IL-2 and IFN-gamma-specific mRNA after antigen stimulation in vitro, while cellular and molecular response to phorbol ester and the calcium ionophore ionomycin (PMA+IM) or anti-CD3 monoclonal antibodies (MoAbs) (OKT3) were comparable to those of healthy control individuals. Here we show that stimulation of these patients' T cells with tetanus toxoid (TT) resulted in dramatically reduced levels of IL-2, IL-9 and IFN-gamma mRNA, while IL-3 gene expression in three patients was comparable or even increased to the healthy controls. As expected, addition of exogenous IL-2 to tetanus toxoid pulsed cultures had virtually no effect on IL-2 transcription, but corrected the defect in IL-9 gene expression, while IFN-gamma mRNA levels were still reduced. In conclusion, these data suggest that recombinant IL-2 alone is not able to induce the IL-9 gene adequately in our patients, but clearly increases IL-9 mRNA levels in combination with tetanus toxoid. PMID- 7871380 TI - Effects of omeprazole and eradication of Helicobacter pylori on gastric and duodenal mucosal enzyme activities and DNA in duodenal ulcer patients. AB - BACKGROUND: Duodenal and gastric content of mucosal enzymes in duodenal ulcer (DU) patients differs from that of controls. The purpose of this study has been to examine the effect of omeprazole and eradication of Helicobacter pylori on mucosal enzymes in DU patients. METHODS: The enzyme activities of seven gastric and duodenal mucosal marker enzymes from the brush border, lysosomes, and mitochondria have been studied. In study I the measurements were made in 29 patients with an active DU before and after 14 days of omeprazole treatment. In study II 22 duodenal ulcer patients were given bismuth subnitrate, oxytetracycline, and metronidazole (triple therapy) for 2 weeks to eradicate H. pylori. Biopsy specimens were taken from the duodenum and the stomach for enzyme measurements and histologic assessment. In study II additional specimens were obtained from the prepyloric region for urease tests and culture of H. pylori. RESULTS: The ulcer healing rates were more than 90% after both omeprazole and triple therapy. H. pylori was eradicated in 86% after triple therapy. The activities of the brush-border enzymes lactase, neutral-alpha-glucosidase, alkaline phosphatase, leucyl-beta-naphthylamidase, and gamma-glutamyltransferase (gamma-GT) increased significantly in the duodenal bulb and the descending duodenum during treatment with omeprazole. No changes in duodenal enzyme activity were detected after triple therapy, whereas a significant fall in gamma-GT and acid phosphatase activities was seen in the stomach. The mucosal DNA in the gastric antrum decreased both after treatment with omeprazole and after triple therapy. CONCLUSIONS: A similar decrease in mucosal DNA of the gastric antrum was demonstrated after both omeprazole and triple therapy with bismuth subnitrate, oxytetracycline, and metronidazole. Omeprazole also affects the content of duodenal mucosal enzymes, whereas triple therapy particularly affects the gastric mucosal enzyme activity. PMID- 7871382 TI - Iron requirements of human lymphocytes: relative contributions of intra- and extra-cellular iron. AB - A supply of iron is of vital importance if lymphocyte proliferation is to proceed successfully and two major sources of iron are available, intracellular stores and serum transferrin. We have investigated the relative importance to the human T lymphocyte of these two sources of iron by depleting them of intracellular iron with the chelator desferrioxamine and by culturing them in medium completely depleted of transferrin iron. The chelator decreased mitogen-stimulated proliferation of human peripheral blood T cells, in a dose-dependent manner, in the absence of extracellular transferrin-iron. By culturing the cells in iron depleted medium, we found that normal lymphocytes proliferated, to a degree, in the absence of extracellular transferrin-iron. We also observed that transferrin receptor mRNA expression was sustained in mitogen-stimulated, iron-deprived lymphocytes, compared with untreated cells suggesting that up-regulation of transferrin receptor may occur in these cells through stabilization of the mRNA. We propose that intra- and extra-cellular iron may contribute to early and late activation processes and that a low level of intracellular iron in lymphocytes, chronically activated in the iron-deficient environment associated with chronic inflammatory diseases such as rheumatoid arthritis, may be a factor in the abnormal cell-mediated immunity associated with such diseases. PMID- 7871383 TI - Apoptosis among CD45RA-/low CD3+ progeny accompanies differentiation of human multinegative thymocytes. AB - Apoptotic cell death is widely believed to be the fate of negatively selected cells in the thymus. In this work we have used multiparameter flow cytometry to analyse reductions in DNA content that occur among differentiating human CD3-4-8- multinegative (MN) thymocytes as they acquire CD3/TCR during in vitro culture. DNA content was measured as the intensity of the DNA-binding dye DAPI. The position of the diploid peak was identified by comparison to chicken red blood cells and to unfractionated uncultured thymocytes which have a sharply defined diploid peak. Apoptosis, was defined as a reduction in DNA content. Apoptotic cell death occurred continuously throughout the 7 day culture period and at the latest stages of culture DNA fragmentation was apparent on gels. Although both CD3- and CD3+ progeny became apoptotic, it was more frequent among the CD3+ progeny of the MN thymocytes. Apoptotic progeny included 60-70% CD3+ cells, while progeny remaining diploid were 8-36% CD3+. Fifty five per cent of CD3+ TCR delta 1+ progeny had less than 75% of the diploid DNA content, while for CD3+ TCR delta 1- progeny only 28% were in this category. CD3+ TCR delta 1+ progeny also comprised 66% of the cycling cells at days 6-7 of culture, suggesting a pattern of rapid cell division followed by apoptotic cell death for this subset. A lack of positive selection in culture may trigger apoptosis among the TCR delta 1 progeny. In contrast, TCR alpha beta progeny arising in culture appear to be less susceptible to apoptosis, perhaps due to their lack of CD4 and CD8. The expression of CD45RA and CD45R0 isoforms were assessed on the progeny of MN thymocytes based on their DNA content. Although 30% of apoptotic progeny expressed CD45RA, it was present at relatively low density compared to that on diploid or cycling cells, 55% of which were CD45RAhi. The majority of apoptotic cells expressed neither CD45RA or CD45R0, but were CD45+, indicating the presence of an isoform not detected by our monoclonal antibodies (MoAbs). This is consistent with speculations that apoptotic cell death among thymocytes is preceded by a transition in CD45 isoform expression. These conditions may model early selective events resulting from high avidity TCR engagement that is independent of CD4 and/or CD8. PMID- 7871384 TI - Analysis of the proliferative T cell response to human cytomegalovirus major immediate-early protein (IE1): phenotype, frequency and variability. AB - Cellular immune responses are important in the recovery from human cytomegalovirus (HCMV) infection. However, little is known about the CD4+ T cell response and the target antigens (Ag) recognized. In this paper, we have analysed the proliferative T cell response of healthy HCMV seropositive (HCMV+) blood donors to recombinant immediate-early proteins expressed in transfected astrocytoma cells and to total HCMV Ags expressed in infected astrocytoma cells. We found that CD4+ T cells were the major cell population that proliferated in the presence of IE or total HCMV Ags. Among healthy HCMV seropositive blood donors with anti-HCMV specific proliferative response, 33-44% also responded to IE Ags. Moreover, in high responders, the precursor frequencies of cells which proliferated in the presence of total HCMV, IE, or IE1 Ags were high (1/103 to 1/255, 1/2785 to 1/7744 and 1/5190 to 1/13531, respectively). In some donors, the anti-IE response was variable over time, whereas the anti-total HCMV Ags response remained constant, which suggests regulation of the anti-IE response in immunocompetent subjects. Our results suggest that the CD4+ anti-IE1 response represents a significant part of the anti-HCMV proliferative response, both at the population level, and within individual immune systems. PMID- 7871385 TI - Native human serum amyloid P component is a single pentamer. AB - Serum amyloid P component (SAP) and C-reactive protein (CRP) are members of the pentraxin protein family. SAP is the precursor protein to amyloid P component present in all forms of amyloidosis. The prevailing notion is that SAP in circulation has the form of a double pentameric molecule (decamer) whereas CRP is a single pentameric molecule. We have investigated by gel permeation chromatography the M(r) of SAP in freshly collected human serum and of SAP purified by carbohydrate affinity chromatography and anion exchange chromatography. SAP was monitored by quantitative immunoelectrophoresis and ELISA, and SAP peak fractions were analysed by use of SDS-PAGE, Western blotting, and electron microscopy. The results indicate that native SAP circulates as a single pentamer, a part of which forms complexes with C4b-binding protein. The properties of SAP changed during purification as indicated by rocket immunoelectrophoresis and electron microscopy. Thus, electron micrographs of purified SAP showed a predominance of decamers. However, the decamer form of SAP reversed to single pentamers when purified SAP was incorporated into SAP-depleted serum. PMID- 7871386 TI - Interleukin-4 gene expression in mercury-induced autoimmunity. AB - Mercuric chloride (HgCl2) induces autoimmunity in Brown Norway (BN) rats, with necrotizing vasculitis in the gut. Circumstantial evidence implicates the Th2 subset of CD4+ T lymphocytes, which produces IL-4. We developed a quantitative polymerase chain reaction (PCR) technique to quantify IL-4 gene expression. A phagemid containing rat IL-4 cDNA was modified to act as the template for a synthetic RNA construct; a known amount of synthetic RNA was added to total RNA from spleen and caecum of BN rats at various times after HgCl2, followed by reverse transcriptase PCR. IL-4 gene expression increased markedly in spleen and caecum after HgCl2. Splenic levels peaked by 10 days at approximately five-times baseline, then returned towards normal as the autoimmune response was spontaneously regulated. Caecal IL-4 expression peaked at 48 h, at which time we observed a previously unreported early phase of tissue injury, with necrotizing vasculitis qualitatively similar to that reported previously in the later phases of the model. These data support a key role for IL-4 in this experimental model of autoimmunity. The quantitative PCR technique can be modified for analysis of other cytokines, allowing further investigation of the role of T cell subsets in this model. PMID- 7871387 TI - Characteristics of immune responses to native and protein conjugated pneumococcal polysaccharide type 14. AB - The immune response to pneumococcal polysaccharide type 14 (PPS-14), induced by native PPS-14 was compared with the response induced by PPS-14 conjugated with CRM197 (PPS-14-CRM197). In our animal model, immunization with PPS-14-CRM197 gave a significant enhancement of anti-PPS-14 serum titres for IgM and IgG, but not for IgA. Also an increase in total number of anti-PPS-14 antibody-secreting cells was found. Using immunohistochemical techniques, a different distribution pattern of specific antibody-containing cells in spleen section after immunization with PPS-14-CRM197 was observed. Furthermore, a higher number of IFN-gamma producing cells was found after immunization with PPS-14-CRM197, as compared with immunization with PPS-14. This enhanced IFN-gamma production may be the cause for enhanced IgG response observed after immunization with PPS-14-CRM197. The specific immune response was less affected by splenectomy in animals immunized with PPS-14-CRM197 than with PPS-14. However, an age-related response to the native as well as the conjugated form of the PPS-14 was observed, since no effect of conjugation with CRM197 was seen in the onset of the immune response to PPS-14 in young animals. In conclusion, our results affirm the hypothesis that conjugation of polysaccharides changes the characteristics of the antigen towards a thymus-dependent antigen. PMID- 7871388 TI - Cloning and sequencing of a unique antigen MPT70 from Mycobacterium tuberculosis H37Rv and expression in BCG using E. coli-mycobacteria shuttle vector. AB - MPB70 is known to be an immunogenic mycobacterial protein secreted in large amounts from Mycobacterium bovis BCG (BCG) Tokyo. The analogous gene for MPT70 was cloned from Mycobacterium tuberculosis H37Rv which produces this protein in only a small amount. The gene encoding 193 amino acid residues including 30 amino acids for the signal peptide, the promoter-like sequence, and the ribosome binding site, was completely identical to that of BCG Tokyo. Computer analysis revealed that the carboxy-terminal half of MPT70 was homologous to amino acid sequences of fasciclin I, osteoblast-specific factor 2 (OSF-2), and human transforming growth factor-beta induced gene product (beta IG-H3). Escherichia coli (E. coli) -mycobacteria shuttle vectors containing mpt70 or mpb70 genes 0.7kbp upstream of the 5' end of them were able to be expressed in BCG Pasteur which is a MPB70 low-producer, but the extent of the expression was not that of a high-producer. PMID- 7871389 TI - In vivo evidence for a non-T cell origin of interleukin-5. AB - Eosinophil myelopoiesis is to a great extent regulated by interleukin (IL)-5. Analysis of IL-5 mRNA in spleen cell preparations by reverse transcription polymerase chain reaction (RT-PCR) revealed the presence of message for this cytokine in uninfected severe combined immunodeficiency (SCID) mice. This message was increased following Mycobacterium avium infection. Normal BALB/c mice had higher levels of expression of IL-5 but the expression of this cytokine was reduced during M. avium infection. Anti-IL-5 monoclonal antibody administration in vivo to SCID mice reduced the number of peritoneal and splenic eosinophils. Gamma interferon (IFN-gamma) had an inhibitory effect of eosinophilopoiesis during infection of SCID mice by M. avium since neutralization of this cytokine increased the number of eosinophils detected in the peritoneal cavity of infected animals. Our results suggest that IL-5 may be produced by cells other than T cells that are both able to respond to infection and are under the control of IFN gamma. PMID- 7871390 TI - Specific and non-specific T-cell activation in high and low antibody-producing mice (selection IV-A). AB - The T-cell regulatory function has been evaluated in lines of mice genetically selected according to the High (H) and Low (L) antibody responsiveness to heterologous erythrocytes. The inhibition of antibody production following CD4+ subset depletion was stronger in L than in H mice. The dose of CD4-specific monoclonal antibody (MoAb) needed for a 50% inhibition of the anti-sheep erythrocyte antibody response was much lower in L mice, even when their responsiveness was improved by repeated antigen injections or by co-injection of lipopolysaccharide as an adjuvant. Lymph-node cells from L mice responded normally or even better than those from H mice to in vitro non-specific triggering via lectins, exogenous superantigens or CD3-specific MoAb. In contrast, the antigen-specific responses of the lymph-node cells from protein primed mice were consistently lower in the Low responder mice. Altogether the results suggest that a defective stimulation of T helper lymphocytes by the antigen contributes to the weak antibody response of L mice. PMID- 7871391 TI - Induction of anti-tumour immunity in syngeneic mice by a leukaemic cell line. AB - Induction of anti-tumour immunity in syngeneic mice by LBC cell line derived from a non-immunogenic T cell leukaemia was studied. The immunization of BALB/c mice with LBC irradiated cells induced in them anti-tumour spleen cells, cytotoxic T lymphocytes and anti-LBC antibodies. The anti-LBC antibodies reacted with components of 14, 16 and 27 kDa present on LB tumour cells, LBC cell line and normal thymocytes, but not with normal lymph node cells. Furthermore, immunization of the autologous hosts with LBC cells partially protected them against subsequent challenge with the original LB leukaemic cells. These findings demonstrate that culture conditions induced modifications in the antigenic properties of the leukaemic cells, allowing LBC cells to stimulate an immune response directed against components expressed at early stages during T cell maturation. These results also suggest that the immune response is responsible for the prolongation of the survival time of the mice inoculated with the parental leukaemic cells. PMID- 7871392 TI - Dendritic leucocytes pulsed with monoclonal antibody-hapten conjugates elicit vigorous primary humoral responses in vivo. AB - Purified dendritic leucocytes (DL) were pulsed briefly in vitro with haptenated monoclonal antibodies (MoAb) to MHC class II and immediately injected i.v. into syngeneic recipients. Strong anti-hapten humoral responses were observed even though only a few picomoles of specific MoAb-hapten conjugates were injected with the DL. In contrast, DL pulsed with control conjugates, i.e. haptenated non binding MoAbs, gave only weak responses. DL thus, can take up, process and present protein antigens even after brief exposure in vitro, and their immunogenicity is enhanced by pulsing with antigen conjugated to specific MoAbs. Furthermore, in the presence of fetal calf serum (FCS), but not normal rat serum, the control MoAb W6/32 (against human MHC class I) bound to DL. The vigorous primary humoral response achieved following this pulsing indicates that it is the binding and the corresponding increased uptake that enhances the immunogenicity of the DL. PMID- 7871393 TI - Differential effects of interleukin-2 and interleukin-7 on the induction of CD4 and CD8 expression by double-negative human thymocytes. AB - Expression of cell surface CD4 (in the absence of CD3/T cell receptor) characterizes an early stage of intrathymic T cell development. Here, we investigated the appearance of CD4 and CD8 expression on highly purified CD4-8- double-negative human thymocytes in response to interleukin (IL)-7 and IL-2. While IL-7 preferentially promoted the appearance of CD4 single-positive and CD4+8+ double-positive thymocytes, IL-2 primarily induced CD8 single-positive thymocytes. A significant fraction of CD4 single-positive cells generated from double-negative thymocytes via IL-7 lacked cell surface CD3 expression. In contrast, the majority of CD8 single-positive cells generated from double negative thymocytes via IL-2 coexpressed CD3. We conclude that IL-7 and IL-2 exert differential effects on the differentiation of early human T cell progenitors. PMID- 7871394 TI - Spleen cells from antithymocyte serum pretreated mice do not induce GVHD but exert increased repopulating activity in irradiated semiallogeneic recipients. AB - Graft-versus-host disease (GVHD) due to allogeneic bone marrow transplantation can be prevented by depleting the T cells from the marrow graft in vitro. However, the elimination of the donor T cells results in a higher frequency of graft failure, secondary infections and, in case of leukaemia, relapse. We found, that, in contrast to normal spleen cells, spleen cells from A or B10 donor mice pretreated with xenogeneic antithymocyte serum (ATS) in vivo did not induce GVHD in non-irradiated (B10 x A)F1 hybrids. Spleen cells of ATS-pretreated A donors did not cause GVHD in allogeneic CBA mice made neonatally tolerant to the A donor strain either. Furthermore, spleen cells from ATS-treated donors did not cause GVHD in irradiated F1 hybrid recipients, moreover, they decreased the lethal effect of irradiation. The in vivo ATS pretreatment improved the repopulating capacity of spleen cells in irradiated syngeneic recipients, too. The effect of the ATS treatment does not rely solely upon the elimination of T cells, since flow cytofluorometric analysis revealed only a partial depletion of both the CD4+ and CD8+ T cells of the ATS-pretreated animals. These observations may also have clinical relevance. PMID- 7871395 TI - Cell proliferation in renal cell carcinoma. A clinical study with special reference to prognosis. AB - As the clinical behaviour of renal cell carcinoma (RCC) varies considerably from case to case, it is important to identify variables capable of predicting outcome in the individual patient. DNA ploidy status, analyzed by flow cytometry (FCM) in 59 patients with stage I disease, showed survival to be significantly better in the diploid than in the non-diploid subgroup. The prognostic value of S-phase fraction evaluated from DNA histograms (S-FCM) was studied in 69 RCC patients. The mean S-phase value was 7.5%, the values being significantly lower in the diploid than in the aneuploid subgroup. Both in the group as a whole and among patients with aneuploid tumors, survival was significantly better in the low (< 7.5%) than in the high (> or = 7.5%) S-phase fraction subgroup. Multivariate analysis showed both the S-phase fraction and tumor stage to be significant independent prognostic variables. Immunohistochemistry (IHC) studies with in vivo iododeoxyuridine labeling (IdUrd-IHC) performed in a series of 33 RCC patients, showed a mean labelling index (LI) of 1.06%. The LI values being significantly lower in diploid than in aneuploid tumors. In a series of 29 RCC patients cell kinetic studies with in vivo IdUrd labeling and subsequent FCM analysis (IdUrd FCM), showed a mean tumor LI of 2.7%, and a mean potential tumor doubling time (Tpot) of 20.3 days (kidney cortex samples 137.7 days). Tpot was found to be a significant prognostic indicator, though as intratumor heterogeneity in Tpot was common it needs to be determined in multiple samples. Proliferating cell nuclear antigen (PCNA) expression evaluated by IHC using the monoclonal antibody PC-10 (PCNA-IHC) in 68 RCC patients, showed the mean PCNA index to be 4.9%, and values being significantly greater in aneuploid than in diploid tumors. Both in the group as a whole and among patients with non-metastatic disease, survival was better in the low (< 3.5%) than in the high (> or = 3.5%) PCNA index subgroup. Four different methods of cell proliferation (S-FCM, IdUrd-IHC, IdUrd-FCM, PCNA IHC) were compared. Comparative analysis according to the Bland and Altman method, showed a good degree of agreement. The results indicated that the different methods seemed to provide comparable information on proliferative activity, although different cell-cycle compartments were monitored.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7871396 TI - The normal mouse urinary bladder reservoir function evaluated by repeated cystometries. Early and late changes after irradiation alone and irradiation combined with cis-diaminedichloroplatinum (II) or cyclophosphamide. PMID- 7871397 TI - [Special aspects of malnutrition in geriatrics]. AB - In 1992 people aged 65 years and over represented 11.9% (men) and 17.2% (women) of the Swiss population, and in 2000 the average 65-year-old man or woman can expect to live about 12 more years. Old age is characterized by multimorbidity, an accumulation of chronic conditions and diseases, and by social isolation. Multimorbidity and isolation (living alone) are the major risk factors for malnutrition. 30-60% of all persons aged 65 years and over show one or more subnormal nutritional parameters. The unspecific and oligosymptomatic clinical picture of malnutrition in the elderly often hinders an early diagnosis, and malnutrition is often misdiagnosed as "wasting away syndrome" of the old. Thus, the nutritional assessment of the elderly should become a routine diagnostic procedure. Detection of malnutrition involves assessment of nutritional parameters including history (eating habits, appetite), anthropometric measurements (weight, height, body mass index, triceps skinfold, midarm circumference), serum proteins (albumin, transferrin, prealbumin, cholinesterase, retinol binding protein), vitamins (B12, folic acid, B1, B2, B6, C and D), minerals and trace elements (zinc, magnesium, calcium, iron), immunologic skin tests and lymphocyte count. Depending on the history and the clinical symptoms, a selected number of these nutritional parameters are assessed. When assessing the nutritional status of the elderly it is important to define the etiologic factors involved. Thus, treatment of underlying causes and refeeding can be streamlined, so that maximum benefit can be obtained for the quality of life of the elderly. PMID- 7871398 TI - [Enteral feeding in tumor patients]. AB - Malnutrition is often a leading sign in cancer patients. Cancer cachexia influences the prognosis of patients in a negative way in that malnutrition decreases the immune response resulting in increased infectious complications. Intensified nutritional support often improves the quality of life. However, no decrease in tumor-associated mortality or increase in survival has thus far been demonstrated. PMID- 7871399 TI - [The traveler returning from the tropics in clinical practice]. AB - Travellers returning from the tropics frequently consult a physician even if they have no actual symptoms. Physical check-ups in asymptomatic returnees rarely detect dangerous conditions. The most common laboratory finding is intestinal parasites. Blood eosinophilia may indicate helminthic infections, such as strongyloidosis, filariasis, schistosomiasis and others. If there are no diagnostically suggestive symptoms a systematic, step-by-step workup is recommended (stool parasitology, serology, and special methods to demonstrate parasites in blood or tissues). The most common symptom of returnees from the tropics is diarrhea, or other disorders of intestinal motility. Appropriate investigations include parasitological and bacteriological tests, and--if the course is more chronic--endoscopy. If diarrhea is associated with fever, systemic infections (e.g. falciparum malaria) must be considered. Fever as a leading sign may mask a number of potentially dangerous infections. If there are no other obvious signs or symptoms indicating a particular etiology, the diagnostic approach should consider first of all those systemic infections, which are potentially life-threatening and can be cured by specific therapy, i.e. bacterial meningitis, falciparum malaria, septicemia (including typhoid fever), extraintestinal amebiasis, and African trypanosomiasis. PMID- 7871400 TI - [Practical guidelines for the administration of artificial nutrition at home (home nutrition) (SAEPE; Swiss Work Group for Enteral and Parenteral Nutrition)]. AB - The number of outpatients with major difficulties in feeding themselves is constantly growing. This results into severe malnutrition resulting in increased infection rate, physical disabilities, skin sores, increased therapeutic costs and poor quality of life. Home nutritional support can cover all nutritional needs but requires appropriate indications, optimal technical management and cautious ethical evaluation. In addition, the overall costs should be covered by an insurance at the time of home nutritional support prescription. Swiss home nutritional support recommendations for practising physicians are presented. PMID- 7871401 TI - [Interstitial pneumopathy]. PMID- 7871402 TI - [Antibiotic treatment of urinary tract infections in hospitalized children]. AB - From 1980 to 1991 237 patients (aged 1 week to 15 years) with moderate to severe urinary tract infection had been treated at the Department of Pediatrics University of Berne, Switzerland. Bacterial etiology, antimicrobial in vitro susceptibility tests, and drug management were retrospectively analyzed. 266 bacterial pathogens were isolated from these patients. Escherichia coli was the most frequent etiologic agent (203), followed by Enterococcus (21), Klebsiella (20), Proteus (12), Pseudomonas (6), Enterobacter (2) and Serratia (2). The overall in vitro susceptibility of these isolates was 61% for aminopenicillins, 80% for co-amoxiclav, 83% for co-trimoxazole and 92% for aminoglycosides. Aminoglycosides were ineffective in vitro only against enterococci. However, since all enterococcal strains were always sensitive to aminopenicillins, none of the pathogens was concomitantly resistant to both aminoglycosides and aminopenicillins. Parenteral therapy had been given initially in 141 patients (59%); aminopenicillin and aminoglycoside in 105, and aminopenicillin alone in 36 cases (cefuroxime instead of aminopenicillin in some patients with suspected allergy to penicillin). 96 patients (41%) were initially treated with oral antibiotics (cotrimoxazole, aminopenicillin or co-amoxiclav). The initial antimicrobial regimen had to be modified in 31 cases (13%). In children with moderate to severe urinary tract infection prompt sterilization of urine and kidneys will prevent or suppress renal tissue lesions. The in vitro susceptibility results observed in the pathogens isolated in the patients prompt us to suggest that the above mentioned goal can only be achieved by an initial regimen consisting of an aminopenicillin and an aminoglycoside compound administered parenterally. PMID- 7871403 TI - [Aortic elongation: merely mimicked in increased thoracic kyphosis? radiologic pathologic correlation]. AB - The purpose of this investigation was to demonstrate that the radiologically "elongated" thoracic aorta corresponds to an increase in anatomical aortic length and is not merely mimicked by increased thoracic kyphosis with shortening of the thoracic cage. 50 consecutive autopsies were included (age at death: 33-90 years, mean 65.1 years). Radiologically, mediastinal width was measured on in vivo posteroanterior radiographs, and a scoring system was used to assess aortic elongation semiquantitatively. The angle of kyphosis was measured on lateral in vivo radiographs that had been obtained in a standardized fashion. With relative aortic length defined as anatomical aortic length divided by body length, there was a statistically significant correlation with radiological mediastinal width and the radiological scoring system (p < 0.001). However, there was no statistically significant correlation between relative aortic length and radiological mediastinal width (p = 0.47) and the radiological scoring system (p = 0.56). Therefore, the radiological diagnosis of aortic elongation appears to correspond to true aortic lengthening. PMID- 7871404 TI - [Surgery of the abdominal aorta in the geriatric population: characteristics and results]. AB - Refinement in surgical technique and perioperative management have considerably improved morbidity and mortality rates of carotid endarterectomy and abdominal aortic surgery, thus allowing a more aggressive approach in the treatment of carotid stenosis, abdominal aortic aneurysm and aorto-iliac occlusive disease in the elderly population (> 70 years). We review our experience with 446 consecutive patients undergoing surgery of the abdominal aorta: 295 patients (mean age 75.5 years) underwent resection of an abdominal aortic aneurysm (asymptomatic but > 5-6 cm, (n = 193), symptomatic (n = 67) or ruptured (n = 35). Additionally, 198 patients were treated surgically for aorto-iliac occlusive disease. A small group of 13 patients was deferred for combined operation, including prior myocardial revascularization and subsequent vascular surgery during the same anesthesia. The majority of patients had several cardiovascular risk factors and/or significant associated diseases. Mortality (< 30 days) was 3.5% following aorto-iliac bypass in the treatment of arterial occlusive disease and 8.4% after aneurysm repair (asymptomatic, symptomatic and ruptured aneurysms all included). 5-year survival was 74% and 64% after repair of aortic aneurysm and treatment of aorto-iliac occlusive disease respectively. On the basis of these results, we believe that major vascular surgery is still justified in elderly patients and can be achieved with reasonable mortality and morbidity. Main goals of the surgery, e.g. to relieve suffering, restore function so as to limit disability and dependency, and prolongation of life expectancy in a dignified and meaningful life-style, are realized the majority of operative survivors. PMID- 7871405 TI - [Participation in multicenter studies as quality control in the therapy of Hodgkin disease: an interim report]. AB - From 1988 to 1992 the Swiss Group for Clinical Cancer Research (SAKK) entered 113 patients with Hodgkin's disease into three stage adapted trials (HD-4-6) from the German Hodgkin Study Group (DHSG). In an interim analysis freedom from treatment failure (FFTF) and overall survival (OS) of the SAKK patients (SAKK-pt) were compared to the remaining study population (GHSH-pt) (median follow-up: 30 months for HD-4 and HD-5, 24 months for HD-6). RESULTS: HD-4: SAKK (n = 16), DHSG (n = 241), FFTF-SAKK: 100%, FFTF-DHSG: 85%, p: ns, OS-SAKK: 100%, OS-DHSG: 99%, p: ns, HD-5: SAKK (n = 66), DHSG (n = 639), FFTF-SAKK: 90%, FFTF-DHSG: 85%, p: ns, OS SAKK: 93%, OS-DHSG: 95%, p: ns, HD-6; SAKK (n = 31), DHSG (n = 411): FFTF-SAKK: 62%, FFTF-DHSG: 68%, p: ns, OS-SAKK: 70%, OS-DHSG: 88%, p < 0.008. The results in the SAKK patients with advanced disease are unsatisfactory. Despite the fact that the treatment was given on time with full doses, 10/30 patients achieved no complete remission (CR). Only one patient relapsed after an initial CR. 6 patients had primary progressive disease. 6 patients died despite conventional salvage chemotherapy. High dose chemotherapy/autologous bone marrow transplantation (HDC/ABMT) was only given to 3 out of 8 potential candidates. Only 2/11 patients are still alive and disease-free after relapse or initial progression. Both had received HDC/ABMT as part of their salvage regimen. This interim analysis identifies a group of patients in which treatment strategies need to be optimized. PMID- 7871406 TI - Ban that embargo. Physicians advocate lifting sanctions against Cuba. PMID- 7871407 TI - Treatment that tightens the belt. Is insurance part of America's obesity problem? PMID- 7871408 TI - MRI goes back to the future. New designs embrace simpler magnets--and lower costs. PMID- 7871409 TI - Faster evaluation of vital drugs. PMID- 7871410 TI - The genetic basis of cancer. PMID- 7871411 TI - Bonobo sex and society. PMID- 7871412 TI - AIDS research priorities. PMID- 7871413 TI - AIDS research priorities. PMID- 7871414 TI - AIDS: modeling epidemic control. PMID- 7871415 TI - AIDS: modeling epidemic control. PMID- 7871416 TI - Casualties expected in takeover battle. PMID- 7871417 TI - Glimmer of hope for T cell booster? PMID- 7871418 TI - Neuronal adhesion molecules signal through FGF receptor. PMID- 7871419 TI - Getting all turned around over the origins of life on earth. PMID- 7871420 TI - DNA goes electric. PMID- 7871421 TI - Out of Africa--at last? PMID- 7871422 TI - Liposomes revisited. PMID- 7871423 TI - Collision of comet Shoemaker-Levy 9 with Jupiter observed by the NASA infrared telescope facility. AB - The National Aeronautics and Space Administration (NASA) Infrared Telescope Facility was used to investigate the collision of comet Shoemaker-Levy 9 with Jupiter from 12 July to 7 August 1994. Strong thermal infrared emission lasting several minutes was observed after the impacts of fragments C, G, and R. All impacts warmed the stratosphere and some the troposphere up to several degrees. The abundance of stratospheric ammonia increased by more than 50 times. Impact related particles extended up to a level where the atmospheric pressure measured several millibars. The north polar near-infrared aurora brightened by nearly a factor of 5 a week after the impacts. PMID- 7871424 TI - The Hubble Space Telescope (HST) observing campaign on comet Shoemaker-Levy 9. AB - The Hubble Space Telescope made systematic observations of the split comet P/Shoemaker-Levy 9 (SL9) (P designates a periodic comet) starting in July 1993 and continuing through mid-July 1994 when the fragments plunged into Jupiter's atmosphere. Deconvolutions of Wide Field Planetary Camera images indicate that the diameters of some fragments may have been as large as approximately 2 to 4 kilometers, assuming a geometric albedo of 4 percent, but significantly smaller values (that is, < 1 kilometer) cannot be ruled out. Most of the fragments (or nuclei) were embedded in circularly symmetric inner comae from July 1993 until late June 1994, implying that there was continuous, but weak, cometary activity. At least a few nuclei fragmented into separate, condensed objects well after the breakup of the SL9 parent body, which argues against the hypothesis that the SL9 fragments were swarms of debris with no dominant, central bodies. Spectroscopic observations taken on 14 July 1994 showed an outburst in magnesium ion emission that was followed closely by a threefold increase in continuum emission, which may have been caused by the electrostatic charging and subsequent explosion of dust as the comet passed from interplanetary space into the jovian magnetosphere. No OH emission was detected, but the derived upper limit on the H2O production rate of approximately 10(27) molecules per second does not necessarily imply that the object was water-poor. PMID- 7871425 TI - HST imaging of atmospheric phenomena created by the impact of comet Shoemaker Levy 9. AB - Hubble Space Telescope (HST) images reveal major atmospheric changes created by the collision of comet Shoemaker-Levy 9 with Jupiter. Plumes rose to 3000 kilometers with ejection velocities on the order of 10 kilometers second-1; some plumes were visible in the shadow of Jupiter before rising into sunlight. During some impacts, the incoming bolide may have been detected. Impact times were on average about 8 minutes later than predicted. Atmospheric waves were seen with a wave front speed of 454 +/- 20 meters second-1. The HST images reveal impact site evolution and record the overall change in Jupiter's appearance as a result of the bombardment. PMID- 7871426 TI - Impact debris particles in Jupiter's stratosphere. AB - The aftermath of the impacts of periodic comet Shoemaker-Levy 9 on Jupiter was studied with the Wide Field Planetary Camera 2 on the Hubble Space Telescope. The impact debris particles may owe their dark brown color to organic material rich in sulfur and nitrogen. The total volume of aerosol 1 day after the last impact is equal to the volume of a sphere of radius 0.5 kilometer. In the optically thick core regions, the particle mean radius is between 0.15 and 0.3 micrometer, and the aerosol is spread over many scale heights, from approximately 1 millibar to 200 millibars of pressure or more. Particle coagulation can account for the evolution of particle radius and total optical depth during the month following the impacts. PMID- 7871427 TI - HST far-ultraviolet imaging of Jupiter during the impacts of comet Shoemaker-Levy 9. AB - Hubble Space Telescope far-ultraviolet images of Jupiter during the Shoemaker Levy 9 impacts show the impact regions darkening over the 2 to 3 hours after the impact, becoming darker and more extended than at longer wavelengths, which indicates that ultraviolet-absorbing gases or aerosols are more extended, more absorbing, and at higher altitudes than the absorbers of visible light. Transient auroral emissions were observed near the magnetic conjugate point of the K impact site just after that impact. The global auroral activity was fainter than average during the impacts, and a variable auroral emission feature was observed inside the southern auroral oval preceding the impacts of fragments Q1 and Q2. PMID- 7871428 TI - HST spectroscopic observations of Jupiter after the collision of comet Shoemaker Levy 9. AB - Ultraviolet spectra obtained with the Hubble Space Telescope identified at least 10 molecules and atoms in the perturbed stratosphere near the G impact site, most never before observed in Jupiter. The large mass of sulfur-containing material, more than 10(14) grams in S2 alone, indicates that many of the sulfur-containing molecules S2, CS2, CS, H2S, and S+ may be derived from a sulfur-bearing parent molecule native to Jupiter. If so, the fragment must have penetrated at least as deep as the predicted NH4SH cloud at a pressure of approximately 1 to 2 bars. Stratospheric NH3 was also observed, which is consistent with fragment penetration below the cloud tops. Approximately 10(7) grams of neutral and ionized metals were observed in emission, including Mg II, Mg I, Si I, Fe I, and Fe II. Oxygen-containing molecules were conspicuous by their absence; upper limits for SO2, SO, CO, SiO, and H2O are derived. PMID- 7871430 TI - Auroral signature of comet Shoemaker-Levy 9 in the jovian magnetosphere. AB - The electrodynamic interaction of the dust and gas comae of comet Shoemaker-Levy 9 with the jovian magnetosphere was unique and different from the atmospheric effects. Early theoretical predictions of auroral-type processes on the comet magnetic field line and advanced modeling of the time-varying morphology of these lines allowed dedicated observations with the Hubble Space Telescope Wide Field Planetary Camera 2 and resulted in the detection of a bright auroral spot. In that respect, this observation of the surface signature of an externally triggered auroral process can be considered as a "magnetospheric active experiment" on Jupiter. PMID- 7871429 TI - Response of the Io plasma torus to comet Shoemaker-Levy 9. AB - Spectroscopic and imaging observations of the Io plasma torus were made in June and July 1994 in conjunction with the encounter of periodic comet Shoemaker-Levy 9 with Jupiter. Characteristic emissions from sulfur and oxygen ions showed a decline of about 30 percent in the extreme ultraviolet and an increase of about 40 percent in the far ultraviolet relative to preimpact observations. Changes in the extreme ultraviolet may be indicative of small changes in the torus electron temperature as a result of quenching of electrons by dust associated with the comet passage. However, no new emission features indicative of fragment dust within the torus were detected. The characteristic torus morphology seen in ground-based imaging was typical of that observed in the past. PMID- 7871431 TI - The fragment R collision: W. M. Keck telescope observations of SL9. AB - The W. M. Keck telescope was used to observe the impact of comet Shoemaker-Levy 9 (SL9) fragment R at a wavelength of 2.3 micrometers on 21 July 1994. The data showed three outbursts. The first flash lasted about 40 seconds and was followed 1 minute after its peak by a second flash that lasted about 3 minutes. A third, longer lasting flare began 6 minutes after the first flash and lasted for 10 minutes. At its maximum brightness, the flare outshone Jupiter. The two short flashes are probably associated with the initial meteor trail and the subsequent fireball, respectively. The bright flare occurred when the impact site rotated into view. These data show that the explosion ejected material at least 1300 kilometers above the visible cloud tops. The luminosity of the impact site during the long bright flare was probably maintained by the release of gravitational potential energy, as this material fell back onto the lower atmosphere. PMID- 7871432 TI - Contribution of STAT SH2 groups to specific interferon signaling by the Jak-STAT pathway. AB - In response to specific ligands, various STAT proteins (signal transducers and activators of transcription) are phosphorylated on tyrosine by Jak protein kinases and translocated to the nucleus to direct gene transcription. Selection of a STAT at the interferon gamma receptor as well as specific STAT dimer formation depended on the presence of particular SH2 groups (phosphotyrosine binding domains), whereas the amino acid sequence surrounding the phosphorylated tyrosine on the STAT could vary. Thus, SH2 groups in STAT proteins may play crucial roles in specificity at the receptor kinase complex and in subsequent dimerization, whereas the kinases are relatively nonspecific. PMID- 7871433 TI - Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors. AB - Many members of the cytokine receptor superfamily initiate intracellular signaling by activating members of the Jak family of tyrosine kinases. Activation of the same Jaks by multiple cytokines raises the question of how these cytokines activate distinct intracellular signaling pathways. Selection of particular substrates--the transcriptional activator Stat3 and protein tyrosine phosphatase PTP1D--that characterize responses to the ciliary neurotrophic factor-interleukin 6 cytokine family depended not on which Jak was activated, but was instead determined by specific tyrosine-based motifs in the receptor components--gp130 and LIFR--shared by these cytokines. Further, these tyrosine-based motifs were modular, because addition of a Stat3-specifying motif to another cytokine receptor, that for erythropoietin, caused it to activate Stat3 in a ligand dependent fashion. PMID- 7871434 TI - A p53-dependent mouse spindle checkpoint. AB - Cell cycle checkpoints enhance genetic fidelity by causing arrest at specific stages of the cell cycle when previous events have not been completed. The tumor suppressor p53 has been implicated in a G1 checkpoint. To investigate whether p53 also participates in a mitotic checkpoint, cultured fibroblasts from p53 deficient mouse embryos were exposed to spindle inhibitors. The fibroblasts underwent multiple rounds of DNA synthesis without completing chromosome segregation, thus forming tetraploid and octaploid cells. Deficiency of p53 was also associated with the development of tetraploidy in vivo. These results suggest that murine p53 is a component of a spindle checkpoint that ensures the maintenance of diploidy. PMID- 7871435 TI - The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. AB - The neuron-restrictive silencer factor (NRSF) binds a DNA sequence element, called the neuron-restrictive silencer element (NRSE), that represses neuronal gene transcription in nonneuronal cells. Consensus NRSEs have been identified in 18 neuron-specific genes. Complementary DNA clones encoding a functional fragment of NRSF were isolated and found to encode a novel protein containing eight noncanonical zinc fingers. Expression of NRSF mRNA was detected in most nonneuronal tissues at several developmental stages. In the nervous system, NRSF mRNA was detected in undifferentiated neuronal progenitors, but not in differentiated neurons. NRSF represents the first example of a vertebrate silencer protein that potentially regulates a large battery of cell type-specific genes, and therefore may function as a master negative regulator of neurogenesis. PMID- 7871436 TI - [Animal experiment study for evaluation of endothelial damage to the aorta after contrast medium administration by ioxithalamate and iomeprol. Quantitative detection of increased cell proliferation with autoradiography]. PMID- 7871437 TI - [Methods for determining organ doses in roentgen diagnosis]. PMID- 7871438 TI - [Diagnostic radiology at university clinics--are new structures desirable?]. PMID- 7871439 TI - [George Edward Pfahler (1874-1957)]. PMID- 7871440 TI - [Significance of skeletal scintigraphy in traumatology from the viewpoint of expert assessment]. PMID- 7871441 TI - Carbon dioxide (CO2)-laser therapy cures macroscopic lesions, but viral genome is not eradicated in men with therapy-resistant HPV infection. AB - BACKGROUND AND OBJECTIVES: We have evaluated the efficacy of CO2-laser in eradicating human papillomavirus (HPV) DNA from genitoanal skin lesions. STUDY DESIGN: Biopsies of 38 male patients with histologically confirmed HPV-infection after an average of 2 years of follow-up were analyzed. Post-treatment biopsies were obtained from all residual or recurrent HPV-suspect (acetowhite) lesions in 23 patients. RESULTS: After an average of three separate CO2-laser treatments, 15 of 38 patients were devoid of any clinical or acetowhite lesions. By in situ hybridization (ISH), the frequency of HPV-types 6/11 decreased from 52% to 26%, and HPV-types 16/18 decreased from 48% to 17%, respectively, in 23 patients biopsied twice. When ISH-negative biopsies were further analyzed with polymerase chain reaction (PCR) and southern blotting (SB) for HPV-16, HPV-types 16/18 were detected in a total of 65% of biopsies before CO2-laser therapy, and in 61% after the therapy. The cure rate achieved with CO2-laser was 39% (15/38) according to clinical, 61% (14/23) according to histopathological, and 26% (6/23) according to molecular biological criteria. The frequency of Bowenoid papulosis was reduced from 57% (13/23) to 17% (4/23). CONCLUSIONS: Although CO2-laser is ineffective in eradicating HPV genome from therapy-resistant penile warts, the treatment reduces the recurrence of atypical changes and visible warts. PMID- 7871442 TI - Factors associated with self-reported STDs: data from a national survey. AB - BACKGROUND AND OBJECTIVES: STD prevention programs need to identify population subgroups and risk behaviors that are associated with higher rates of disease. GOAL OF THE STUDY: To see what levels of STD experience were reported by respondents to a national survey and what factors were associated with self reported STDs. STUDY DESIGN: The survey data are from Cycle IV (1988) of the National Survey of Family Growth (NSFG), a nationally representative household based sample of 8450 women ages 15 to 44 years. We examined characteristics of survey respondents who reported STD experience, characteristics of STD cases reported to the national STD surveillance system, and factors related to self reported STDs using multiple logistic regression. RESULTS: The self-reported survey data indicate that the majority of respondents who ever had gonorrhea (55%) were white, but white women account for only 19% of the annual cases in the surveillance system. Logistic regression analysis of survey data indicates factors associated with reported gonorrhea experience, sexual behavior, race/ethnicity, socioeconomic background, perceived risk of AIDS, receiving birth control education, and region of residence. Reporting of chlamydia appears to be strongly related to knowledge of this infection. CONCLUSIONS: Because of basic differences in the statistics being compared, we cannot rule out other explanations. Our results suggest that the surveillance data may reflect underreporting of higher socioeconomic groups making use of private health care. Survey data, on the other hand, are probably affected by underreporting of STD experience. Questions to measure STD experience, treatment, and source of care on surveys of this type would greatly increase the understanding of STDs in the national population. PMID- 7871443 TI - Detection of human papillomavirus types in cervical lesions of patients from Taiwan by the polymerase chain reaction. AB - BACKGROUND AND OBJECTIVES: The association of human papillomavirus (HPV) infection with cervical carcinoma is well documented. The HPV types in cervical lesions of patients from Taiwan are analyzed by the polymerase chain reaction (PCR). STUDY DESIGN: DNA was extracted from paraffin-embedded, formalin-fixed tissues using a sonication method. PCR was performed using type-specific primers for the presence of HPV types 6, 11, 16, 18, 31, and 33 DNA. Amplified product was subjected to gel electrophoresis and Southern blot hybridization analysis. RESULTS: A total of 129 cervical lesions and normal cervical biopsies were examined. Histologic examination revealed a spectrum of lesions, which were classified as condyloma acuminata (AC), condyloma (CL), koilocytosis (KL), various grades of cervical intraepithelial neoplasia (CIN I, II, and III), carcinoma in situ (CIS), and invasive carcinoma (ICa). Of 114 cervical lesions, 65% (26 of 40) of AC; 61% (11 of 18) of CL; 20% (2 of 10) of KL; 25% (1 of 4) of CIN I; 69% (9 of 13) of CIN II; 80% (12 of 15) of CIN III; 83% (5 of 6) of CIS; and 100% (8 of 8) of ICa were positive for at least one type of HPV by the PCR. Among the 74 HPV-positive specimens, 19 (26%) were detected with multiple types. HPV DNA was detected in the cervical biopsies of 1 of 15 (6.7%) normal individuals. CONCLUSION: Excluding AC, HPV 6 and/or 11 (HPV 6/11), HPV 16 and/or 18 (HPV 16/18), and HPV 31 and/or 33 (HPV 31/33) were detected in 40% (19 of 48), 71% (34 of 48), and 12% (6 of 48) of neoplastic lesions of patients from Taiwan respectively. These findings are compatible with those reported by others worldwide. PMID- 7871444 TI - Pattern of sexually transmitted diseases in a Malagasy population. AB - BACKGROUND: Data concerning the spectrum and antimicrobial susceptibility of STDs in Madagascar are scarce. OBJECTIVES: Improvement of STD patient management in Madagascar. GOAL OF THE STUDY: Assessment of the spectrum of STDs and improvement of therapy. STUDY DESIGN: Etiologic study of 400 patients (169 men, 231 women) under consultation at the major STD service in Antananarivo for one or more of the STD syndromes, urethral discharge, cervicovaginal discharge, genital ulcers, or condylomata according to a fixed diagnostic schedule. RESULTS: Of genital ulcers, syphilis accounted for 46%, lymphogranuloma venereum for 24%, chancroid for 16%, and herpes for 1%. Of the syphilis cases, 51% presented as condyloma lata. Discharge was found in 124 men and 210 women. Counting concomitant infections separately, gonorrhea occurred in 69% of the men and 20% of the women with discharges, chlamydia infection in 42% and 52%, trichomoniasis in 9% and 31%, candidiasis in 12% and 30%. Bacterial vaginosis was found in 37% of the women with discharges. In 32% of male and 71% of female gonorrhea cases, there was concurrent chlamydia infection. Infection with HIV 1 or 2 was not detected. Determination of the antibiotic susceptibility of Neisseria gonorrhoea revealed high efficacy of ampicillin, ciprofloxacin, and spectinomycin; but frequent resistance to tetracycline and cotrimoxazole. CONCLUSIONS: High priority should be given to the management of infections with chlamydia and with Treponema pallidum as well as to educational measures to increase awareness of genital ulcer disease. PMID- 7871445 TI - HIV infection among female injection-drug users recruited in community settings. AB - BACKGROUND AND OBJECTIVES: To identify relationships between sexual behavior, drug use, and HIV infection among female injection-drug users (IDUs) recruited in community settings. STUDY DESIGN: Risk analysis of 407 survey questionnaires and matched HIV serologies (n = 403) from female IDUs recruited from community settings in 3 inner-city neighborhoods in San Francisco during 1991 and 1992. RESULTS: The HIV seroprevalence of our sample was 11.4%. Fifty-four percent reported using crack cocaine in the past 30 days. HIV seroprevalence was 10.5% among crack cocaine smokers and 12.5% among nonsmokers. In multivariate analysis, HIV infection was associated with a history of sex for money exchanges (adjusted odds ratio [AOR] = 3.11; 95% confidence interval [95% CI] = 1.37, 7.02); history of syphilis (AOR = 3.30; 95% CI = 1.36, 7.99); and African American ethnicity (AOR = 5.31; 95% CI = 2.05, 13.73). Crack smoking in the past 30 days (AOR = 0.33; 95% CI = 0.15, 0.71) and having a current steady sexual partner (AOR = 0.48; 95% CI = 0.24, 0.94) were both inversely associated with HIV infection in the multivariate model. None of our injection-related variables were predictive or protective of HIV infection, when controlled for the above factors. CONCLUSIONS: Unprotected heterosexual activity is a principal risk factor for HIV infection among female IDUs in San Francisco. Greater reported sexual risk behavior of crack smokers was not reflected by a higher HIV rate at present, perhaps because of lower prevalence of HIV among their sexual partners. PMID- 7871446 TI - Epidemiologic study of Chlamydia trachomatis infection in pregnant women. AB - GOAL OF THE STUDY: The presence of Chlamydia trachomatis in the cervical canal was investigated in 10,980 married pregnant women and 1,792 unmarried pregnant women who underwent artificial abortions in Hokkaido. STUDY DESIGN: Cervical canal smears were screened for C. trachomatis in pregnant patients. RESULTS: In the married women, the detection rate of C. trachomatis was 5.6% (615 of 10,980 cases). In the unmarried women, the detection rate of C. trachomatis was 15.2% (272 of 1,792 cases). Stratification of the data on the detection of C. trachomatis as a function of the subjects' age showed that, for both the married and the unmarried women, the detection rate increased as the age of the subjects decreased. Analysis of the detection rate of C. trachomatis as a function of the year revealed that it had not changed since 1986. CONCLUSIONS: The findings in this study show that there has been an epidemic of asymptomatic C. trachomatis infections in Hokkaido, especially in young women. PMID- 7871447 TI - Diversity of isolates of penicillinase-producing Neisseria gonorrhoeae (PPNG) in Honolulu, Hawaii: 1982-1991. AB - BACKGROUND AND OBJECTIVES: Gonococcal infections caused by penicillinase producing Neisseria gonorrhoeae (PPNG) isolates have increased in geographic distribution and prevalence. It was postulated that PPNG strains would become endemic in Honolulu and that, in turn, this city would serve as a reservoir for the introduction of PPNG strains into the continental United States. GOAL OF THIS STUDY: To assess the role of Honolulu as a reservoir for PPNG strains by assessing the diversity and persistence of PPNG strains between 1982 and 1991. STUDY DESIGN: A total of 432 PPNG strains were characterized by auxotype/serovar (A/S) class and plasmid content, and their distribution during the 10-year period was studied. RESULTS: Of 432 isolates, 373 (86.4%) possessed a 4.4-Mdal beta lactamase plasmid; 39 (9.0%) possessed a 3.2-Mdal beta-lactamase plasmid; and 20 (4.6%) possessed a 3.05-Mdal beta-lactamase plasmid. A total of 53 A/S classes were identified. Asian, African, and Toronto PPNG strains belonged to 49 (92.5%), 15 (28.3%), and 11 (20.7%) A/S classes, respectively. Though all Toronto PPNG strains possessed a 24.5-Mdal conjugative plasmid, these plasmids could not be transferred by conjugation. Although some apparent microepidemics of PPNG strains were identified, most strains were isolated sporadically. CONCLUSIONS: A large number of different strains have been associated with PPNG infections in Honolulu, but there was no evidence that any strain persisted endemically during the study period. These observations have important implications for the design and assessment of community gonorrhea control strategies. PMID- 7871448 TI - Effects of Cetyltrimethylammonium naproxenate on the adherence of Gardnerella vaginalis, Mobiluncus curtisii, and Lactobacillus acidophilus to vaginal epithelial cells. AB - BACKGROUND AND OBJECTIVES: A decreased concentration or total disappearance of Lactobacillus acidophilus in the vagina constitutes a frequent observation in bacterial vaginosis. GOAL OF THE STUDY: Cetyltrimethylammonium naproxenate has been evaluated in vitro to detect antiadhesive properties at subinhibitory concentrations for Gardnerella vaginalis and Mobiluncus curtisii to vaginal epithelial cells (VEC). STUDY DESIGN: Bacterial strains 14C- and or 3H-labeled were tested for adherence and competition to binding sites in VECs before and after treatment at sub-MIC with cetyltrimethylammonium naproxenate. RESULTS: In control tests of adherence, G. vaginalis and M. curtisii had their maximal adhesion at pH 5.4, L. acidophilus at pH 4.4. Preincubation of G. vaginalis and M. curtisii with cetyltrimethylammonium naproxenate 2.5 mg/mL (subinhibitory concentration) at pH 5.4 reduced adherence to VECs respectively by 48.3% and 34.1%. The same treatment of L. acidophilus showed no statistically significant difference. Treatment of VECs alone did not modify adherence. Competition tests between L. acidophilus and G. vaginalis and between L. acidophilus and M. curtisii showed that, in small quantities, L. acidophilus could compete with G. vaginalis and M. curtisii for binding sites in VECs at pH 4.4, when pretreated with cetyltrimethylammonium naproxenate. At a higher pH (4.8 and 5.4), L. acidophilus in higher quantities did not compete for binding sites occupied by G. vaginalis and M. curtisii. CONCLUSIONS: Cetyltrimethylammonium naproxenate at subinhibitory concentrations modifies the adhesiveness of G. vaginalis and M. curtisii to VECs, reducing it by 48.3% and 34.1%, respectively. Adhesion of L. acidophilus to VECs is not impaired by pretreatment with cetyltrimethylammonium naproxenate at pH 4.4, even if they are in low number and compete for binding sites against pathogens. At higher pH levels, L. acidophilus did not compete for binding sites occupied by G. vaginalis and M. curtisii. PMID- 7871449 TI - Single-dose ciprofloxacin for the treatment of uncomplicated gonorrhea: a worldwide summary. AB - BACKGROUND AND OBJECTIVES: Antibiotic therapy for Neisseria gonorrhoeae infections has evolved owing to the development of resistance to penicillin and tetracycline therapy. A variety of antimicrobials, including the fluoroquinolones, have been proposed as useful alternatives. GOAL OF THE STUDY: To evaluate the efficacy and safety of oral ciprofloxacin as single-dose treatment for urogenital and extragenital gonococcal infections. STUDY DESIGN: 1180 patients with uncomplicated gonococcal infection received single-dose ciprofloxacin regimens ranging from 100 mg to 2000 mg to demonstrate microbiologic efficacy and to determine the minimum effective dose. Eight of 18 studies were randomized, controlled trials with ampicillin/probenecid, amoxicillin/probenecid, ceftriaxone, or spectinomycin as control drugs. RESULTS: Although a ciprofloxacin dose-response was not detected, 250 mg was used in most of the studies. Among 815 patients with 910 infected sites receiving 250 mg of ciprofloxacin, bacteriologic eradication was achieved in 563 (100%) male urethral, 199 (100%) female cervical, 101 (99%) male and female rectal, and 47 (96%) male and female pharyngeal sites. CONCLUSION: Although the World Health Organization and the Centers for Disease Control and Prevention have identified 500 mg of ciprofloxacin as a single-dose treatment regimen for uncomplicated gonorrhea, the clinical data from the multinational studies indicate that a 250 mg single-dose of ciprofloxacin is equally effective in the management of uncomplicated gonorrhea, including extragenital sites of infection. PMID- 7871450 TI - Estimating the basic reproductive rates of Neisseria gonorrhoeae and Chlamydia trachomatis: the implications of acquired immunity. AB - BACKGROUND AND OBJECTIVES: The basic reproductive rate of and STD is an important parameter from which the success of intervention strategies can be predicted. GOAL OF THE STUDY: To evaluate different methods to estimate the basic reproductive rate. RESULTS: Two different methods of estimating the basic reproductive rates of Neisseria gonorrhoeae and Chlamydia trachomatis yielded discrepant results. One of the methods, which is based on the assumption of the absence of acquired immunity, yielded unrealistically low estimates of the basic reproductive rates. CONCLUSION: In conjunction with other epidemiologic evidence, we infer that some form of acquired immunity to these pathogens must exist and discuss its implication for control. PMID- 7871451 TI - Trichomoniasis: perspectives in declining prevalence in a GUM clinic. PMID- 7871452 TI - Pension coverage among the baby boomers: initial findings from a 1993 survey. AB - Using data from a series of supplements to the Current Population Survey, this article presents findings on workers' coverage under employer-sponsored retirement plans in 1993, and recent trends in coverage. The analysis focuses on workers 25-54, a group that includes the baby boom generation. Among all wage and salary workers in this age range (including government employees and part-time workers), 55 percent reported participating in a retirement plan on their current primary jobs, and an additional 3 percent were covered from other jobs. After a modest decline in the early 1980's, the coverage rate has remained essentially unchanged over the past 10 years, and limited data suggest that the baby boomers are doing about as well on pension coverage as older workers at similar points in their careers. Beneath this relative stability in overall coverage, however, at least two important changes have occurred: a significant narrowing of the gender gap in coverage and a shift in types of retirement plans. Increasing numbers of workers are being covered solely by 401(k)-type plans, a development that raises new uncertainties about the form and amount of future benefits. On the other hand, limited data in this study suggest that 401(k) plans may be serving their intended purpose for the majority of workers who have them. PMID- 7871453 TI - Disability trends in the United States: a national and regional perspective. AB - Between 1978 and 1993, the number of persons receiving disability benefits under either the Supplemental Security Income program or the Old-Age, Survivors, and Disability Insurance program increased more than 43 percent--from 4.7 million to 6.7 million. In 1993, 4.08 percent of the U.S. resident population aged 18-64 were receiving a disability benefit under one or both of the programs, compared with 3.37 percent in 1978. This ratio had declined to 2.93 percent in 1983. The article examines the change in growth since 1975 in each of the two disability programs and provides an overview of key legislative changes occurring during the period. The emphasis is on regional and State changes during the 1987-92 period, identifying those areas where growth has been the most dramatic. PMID- 7871454 TI - The advantages and disadvantages of different social welfare strategies. AB - The following was delivered by the author to the High Level American Meeting of Experts on The Challenges of Social Reform and New Administrative and Financial Management Techniques. The meeting, which took place September 5-7, 1994, in Mar del Plata, Argentina, was sponsored by the International Social Security Association at the invitation of the Argentine Secretariat for Social Security in collaboration with the ISSA Member Organizations of that country. PMID- 7871455 TI - Work efforts of disabled-worker beneficiaries: preliminary findings from the new beneficiary followup survey. AB - This article represents a preliminary investigation of factors influencing the decision of disabled-worker beneficiaries to look for employment and to return to work. Using the New Beneficiary Followup Survey and the special add-on frame of beneficiaries who had earnings, the article analyzes the impact of vocational rehabilitation (VR), work incentives, and employer workplace accommodations on the decision to return to work. Also examined are the reasons beneficiaries gave for deciding to look for work, job search methods, and the types of jobs that they were looking for. The research indicates that most beneficiaries look for work for financial reasons, for example, out of economic necessity or to improve their standard of living. Only 1 in 4 reported that they had received VR services and most indicated that it did not help them on the job. Most beneficiaries (80 percent) were unaware of work incentive provisions at the time they returned to work. Nearly half (42 percent) reported receiving workplace accommodations from their employer. Further research is planned to help assess the return to work experience. PMID- 7871456 TI - Plan for a new disability claim process. AB - The Social Security Administration has released a plan to dramatically improve the agency's disability determination process. When fully implemented, this new process will facilitate better and faster service for the millions of individuals who apply for Social Security and Supplemental Security Income disability benefits each year. The Commissioner recently created a Disability Implementation Task Force that has already begun the extensive planning needed to make the new disability process a reality. The changes are expected to be made over a 5-year period, beginning later this year. We are reprinting from the plan the Commissioner's message; the broad description of the new process, with detailed elements of the process to be developed; the costs and benefits; and the implementation strategy. Most of the information contained in the first section of the plan, Case for Action, was published in our last issue (Social Security Bulletin, Summer 1994, pp. 51-55). The full report, including the Appendices, can be obtained by calling 1-410-966-8255 or by writing to SSA, Disability Process Reengineering Project, P.O. Box 17052, Baltimore, Maryland 21235. PMID- 7871457 TI - The hazard of mortality among aging retired- and disabled-worker men: a comparative sociodemographic and health status analysis. AB - This article reports on the hazard of mortality of aging retired- and disabled worker men over the decade after they became Social Security beneficiaries. Basic patterns of mortality rates are described using data from the 1982 New Beneficiary Survey linked to administrative records. The article examines the association of increasing age, race, socioeconomic status, private health insurance, and other demographic and health characteristics with the duration of life between the two groups of men, using statistical models. Over the decade, the hazard of death for retired workers significantly increased with aging and with lower socioeconomic status. The hazard of death for the disabled was significantly associated with being black. PMID- 7871458 TI - Protection against income loss during the first 6 months of illness or injury. AB - This note has reviewed the protection of workers against income loss during the first 6 months of illness or injury. The national income loss due to short-term sickness and disability during the first 6 months of illness, as expressed by pre tax wages, was about $69.6 billion in 1991. Of this amount, about $46.5 billion (66.8 percent) was replaced by income-protection programs, including paid sick leave; group insurance; temporary disability insurance, under statutory State provisions; individual insurance; workers' compensation; general assistance; and the 6th month of the Social Security Disability Insurance program. In 1991, within the private sector, wage and salary workers lost $47.2 billion because of nonoccupational illnesses or injuries, of which $17.6 billion (or 37.3 percent) was replaced. Coverage against income lost because of illness in the U.S. workforce favors full-time professional and technical employees with longer service in large or medium firms, and especially favors public sector employees. The lowest level of coverage is provided to part-time employees with limited seniority who work in production and related areas in small, private establishments. About 70 percent of wage and salary workers in the private sector have some protection through their employment against earnings losses caused by short-term illness or injury; 44 percent of these workers have short-term disability insurance, and half have sick leave coverage. PMID- 7871459 TI - An old mouth speaks out: a geriatrician's message to the dental profession. PMID- 7871460 TI - Recognizing and reporting dental violence: a survey of dental practitioners. AB - A survey was sent to 1,000 Colorado dentists to evaluate their recognition and reporting of child, elder, and spouse abuse. Approximately 40% of the dentists returned the survey. In answering questions about suspected and reported cases of child abuse, 29% of the respondents indicated that they had suspected at least one of their patients to be a victim of child abuse, while 14% of the respondents had actually reported at least one case. Only 7% of the responding dentists had ever suspected a case of elder abuse, while just over 1% indicated that they had reported at least one suspected elder abuse case to authorities. When asked about their recognition and reporting of spouse abuse, 30% of the responding practitioners had suspected at least one case, while only 3% had ever actually reported a case to authorities. The overwhelming majority of responding dentists indicated that they needed to know more about child, elder, and spouse abuse. PMID- 7871461 TI - Oro-dental management of patients with familial dysautonomia. AB - Oro-dental abnormalities are quite frequent in familial dysautonomia. The practitioner should be familiar with this disorder, which represents a "human model" for chronic progressive oro-dental denervation. Self-injurious behavior is caused mainly by profound sensory loss. An appropriate preventive and therapeutic approach that was developed in our clinic and adapted for the special hazards of dentistry in youngsters with systemic autonomic dysfunction may improve the life quality of this particular population. PMID- 7871462 TI - Infective endocarditis in a patient with Hodgkin's lymphoma: a case report. AB - A common sequela of certain malignancies is nonbacterial thrombotic endocarditis (NBTE), a phenomenon in which sterile fibrin/platelet aggregates are deposited onto normal cardiac valves. These verrucae represent a predisposing factor for the initiation of infective endocarditis following a bacteremia. This paper presents a case history which is highly suggestive of infective endocarditis which occurred as a result of multiple odontogenic abscesses in a patient with Hodgkin's lymphoma. The case illustrates the important role that the dentist can play in the management of cancer patients and emphasizes a wholistic concept of medical care in which the dentist is an integral member of the health-care team. PMID- 7871463 TI - Neuropathological chewing: a dental management protocol and treatment appliances for pediatric patients. AB - Neuropathological chewing in hospitalized, comatose patients can occur from severe brain damage following a closed head injury, hypoxia, and septic shock. The dental management protocol developed by the Department of Dentistry at the Royal Children's Hospital, Melbourne, Australia, is presented. Treatment appliances utilizing a mandibular cast-silver cap splint with acrylic bite blocks and a maxillary mouthguard with acrylic bite blocks are discussed. PMID- 7871464 TI - Informed consent and the elderly dental patient. AB - The fastest growing segment of the population is currently comprised of those people 65 and older. The competency of these elderly individuals is often called into question when decisions about medical care are to be made. This article explores the concepts of a valid informed consent and provides an overview of competency assessment for the practitioner as it pertains to the geriatric dental patient. PMID- 7871465 TI - Risk factors for and the prevention of root caries in older adults. AB - With the absolute and relative number of elderly people rising in most countries, it is essential that dental practitioners be knowledgeable about the normal changes and disease processes that occur in aging individuals. Especially prevalent in the aging population is root surface caries. Several variables may increase the risk of developing root surface caries. Among these are poor oral hygiene, microbial plaque, periodontal disease, gender (male), coronal caries, dietary habits, xerostomia, low socio-economic status, and infrequent dental visits. While each of these has an effect, plaque seems to have the greatest influence on the susceptibility of teeth to root decay. Improved oral hygiene and regular dental visits, combined with the use of fluoride, may continuously convert active root caries lesions to inactive. In fact, prophylactic programs are more effective in converting active to inactive rather than preventing the development of new lesions. The conscientious dental practitioner must identify his/her older patients at risk for developing root lesions and place a major emphasis on the prevention and treatment thereof. PMID- 7871466 TI - Implications of giant cell arteritis in older adults. AB - Giant cell arteritis, a vascular inflammatory disorder of unknown etiology, is most often observed in Caucasian females over age 50. The vascular changes, involving the cranial arteries, result in oral and perioral symptoms as well as headache and scalp tenderness. Since involvement of the ophthalmic artery can result in visual disturbances and sudden blindness, dentists must be familiar with the signs and symptoms of this condition and refer patients for immediate medical assessment and care. Oral corticosteroid therapy is the treatment of choice. PMID- 7871467 TI - Prevalence of oral methicillin-resistant Staphylococcus aureus in an institutionalized veterans population. AB - Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial pathogen now of great concern in nursing homes and other institutional settings. MRSA has been well-documented to inhabit the nares, skin wounds, and respiratory tract, but little is known about its presence in the oral cavity. In this study, all patients admitted to an 80-bed VA extended care facility were cultured weekly for 12 weeks to detect the presence of MRSA in the nares, wounds, in-dwelling devices, and the oral cavity. Of a total of 107 participating subjects, 20 cultured positive for oral MRSA, yielding a prevalence of 18.7%, compared with 19.6% prevalence in the nares--the traditionally accepted screening site for MRSA. There was a 91.6% agreement between oral and nasal carriage in subjects, but four of 107 subjects (3.7%) cultured positive for oral MRSA without evidence of nasal carriage. These results suggest that oral MRSA may be more common than previously thought in high-risk settings, with a prevalence comparable with that of nasal infection. Further investigation is necessary to characterize the factors associated with the presence of MRSA in the oral cavity. PMID- 7871468 TI - Assessment of the oral health status of the medically compromised homebound geriatric patient: a descriptive pilot study. AB - This pilot study was designed to assess the oral health status of homebound elderly and determine their dental care needs. Fifty-one subjects enrolled in a hospital-based home care program were recruited for this study. Subjects were visited in their homes by both a dentist and a physician. Care plans and medications were reviewed for each subject. Initial assessments to receive informed written consent were conducted by the physician. Oral health assessments by the dentist included comprehensive examinations for soft tissue pathology, periodontal health, caries, restoration, and tooth condition, as well as existing prosthesis assessment, plaque index, and grip strength. A Physical Self Maintenance Scale was administered in order to determine the level of dependence of this population for their oral hygiene self-care. The oral health status of these homebound elderly was found to be poor, with 84% of the subjects requiring dental care. PMID- 7871469 TI - Pulpal obliteration related to long-term glucocorticosteroid medication. AB - Glucocorticosteroids (GCS) are used in the treatment of chronic autoimmune diseases and many long-term illnesses. While these drugs may be considered essential for the patient's health, adverse reactions do occur. The incidence of adverse reactions depends upon the dose level and the duration of treatment. Three case reports of patients on long-term GCS therapy are presented. Pulpal obliteration was assessed by radiographic records. In all instances, pulpal obliteration to some degree is described; however, the rate and extent of pulpal obliteration in the mature dentition seem greater than those occurring in the immature dentition. In the cases reported, the greatest dentin deposition appeared to occur on the roof of the pulp chamber, indicating that the pattern of dentin deposition by pulp tissue in GCS-treated individuals is different from that of the normal aging process. PMID- 7871470 TI - Dental condition and weight loss in institutionalized demented patients. AB - This reports the results of a retrospective clinical study evaluating the role of dentures on weight maintenance in an institutionalized demented population. Records of 57 demented long-term (greater than 3 months) residents of the Department of Veterans Affairs Medical Center, Washington, DC, Nursing Home Care Unit were evaluated to determine body weight, mental acuity, independence in daily living, and dental condition. Fourteen (24%) of the patients possessed dentures, 19 (33%) were edentulous and functioned without dentures, while 24 patients (42%) were dentate. Overall mean weight change was -2.03 lbs +/- 0.81 lbs in 3 months. There was no significant difference in weight loss based on dental condition. There was, however, an apparent correlation of weight loss and mental acuity. Thus, it was concluded that dentures did not influence weight maintenance among institutionalized demented patients. PMID- 7871471 TI - Four maxillary incisors: a case report. AB - This case report describes the dentofacial morphology and treatment of a 9-year old female who presented with four maxillary incisors, and a combination of rare oral and cervical vertebral anomalies. The patient had a Class II division I malocclusion which was complicated by the presence of supernumerary permanent teeth: two supplemental maxillary central incisors, and a supplemental mandibular central incisor. She also had abnormalities of the cervical vertebrae, which were symptom-free. In addition, a number of surgical procedures had been performed in early childhood to treat a benign oral teratoma, cleft tongue, and an isolated cleft of the secondary palate. The dental treatment involved the extraction of the two most centrally placed maxillary central incisors, and the alignment of the maxillary arch with fixed orthodontic appliances. PMID- 7871472 TI - A review of chlorhexidine and its use in special populations. AB - The purpose of this paper is to review the mechanism of the action, safety, and side-effects of chlorhexidine, and to provide guidelines for its use in special populations. Chlorhexidine has been used orally since 1959, primarily for the control of dental plaque. Chlorhexidine is a safe material, with low toxicity potential when used correctly. The most conspicuous side-effects are the development of yellow-brown stains on the teeth, tongue, and at the margins of anterior restorations, and an alteration in taste sensation. The use of chlorhexidine is indicated in developmentally disabled, medically compromised patients, and in dependent elderly populations, since these groups are often physically unable to remove plaque by mechanical means. Clinicians should not prescribe chlorhexidine indiscriminately for all patients, however, until analyzing its efficacy, safety, and side-effects. PMID- 7871473 TI - Prevalence and demographic correlates of tooth loss among the elderly in the United States. AB - The aging of the United States population and the contribution of tooth loss to oral health make it important to describe tooth loss among the elderly in this country. Data from the National Survey of Oral Health in US Employed Adults and Seniors: 1985-1986, conducted by the National Institute of Dental Research, were analyzed to examine the prevalence and demographic correlates of tooth loss among the elderly. Results show that there were important differences in tooth loss among subgroups of the elderly sample (overall n = 5,649 persons aged 65+ years attending senior centers). The oldest seniors and those with the least education or income were the most likely to be edentulous. The oldest dentulous seniors, blacks, those with the least education or income, and those who lived in New England or the Northeast had the fewest number of teeth present. These findings suggest that efforts to reduce tooth loss among the elderly should target those with the least education and income. PMID- 7871474 TI - Oral-surgeon-reported incidence of complications related to simple extractions in adults. AB - This study examined the incidence of complications related to simple forceps extractions in male and female adults. A total of 413 patients (156 young adults, 150 middle-aged, and 107 older adults) presenting for extraction in the practices of 20 privately practicing oral surgeons was followed prospectively for a 30-day period. A total of 74 patients had complications. No age differences were found in the incidence of operative or postoperative complications. Reasons for extraction, number of teeth extracted, or the time required for extraction did not vary among the age groups. Oral surgeons were more likely to prescribe postoperative analgesic medications to patients already on medications. Tendency to prescribe analgesic medications was unrelated to patient age. Results indicate that among community-dwelling adults, age is not a risk factor for complications resulting from simple extractions. PMID- 7871475 TI - Oral side-effects of the most frequently prescribed drugs. AB - Oral side-effects and their respective prevalence rates for the 200 most frequently prescribed drugs for 1992, as measured by IMS America's National Prescription Audit is reviewed. Accounting for duplication due to brand and generic name listings, the actual number of different medications covered was 131. The results of this review are presented in a table and include the oral side-effects and prevalences as reported in the literature. The three most frequent side-effects encountered with these medications were xerostomia (80.5%), dysgeusia (47.5%), and stomatitis (33.9%). The included table should fill the need for a ready reference for dentists in monitoring and counseling patients regarding the potential oral side-effects of the medications. PMID- 7871476 TI - Autotransplantation of 45 teeth to the upper incisor region in adolescents. AB - Young, growing individuals with one or more upper incisors missing due to trauma, agenesis or extraction of abnormal teeth can be treated with autotransplantation to restore aesthetics and function and to preserve the volume of the alveolar process. Studies have been performed to evaluate the prognosis, indicating a good prognosis, especially if an immature transplant is available, developed to 3/4 of the full root length. The purpose of this study was to analyse the result of all autotransplantation of teeth performed to the upper incisor region between 1979 and 1990 at the Department of Oral Surgery, Eastmaninstitutet, Stockholm, Sweden. The material consists of 23 immature and 22 mature teeth in 40 patients with a mean age of 12 years. They were systematically followed up clinically and roentgenologically for up to four years after surgery. 22 of the 23 immature (96%) and 18 of the 22 mature teeth (82%) were observed to be without serious complications. The complications occurred, with one exception, within the first year of observation. The conclusion drawn from this study is that autotransplantation to the upper incisor region can be performed with a good prognosis, both for mature and immature teeth. PMID- 7871477 TI - Quality of periodontal healing. III: Periodontal width following long epithelial junction or reparative cementum formation. AB - The purpose of the present study was to compare the width of the periodontal space following two different marginal periodontal healing reactions (long epithelial junction and connective tissue healing involving formation of reparative cementum) with the width of normal periodontium, either intact or following reattachment. Twelve permanent lateral incisors in monkeys from a previous experimental study on periodontal wound healing on denuded surfaces were selected based on strict healing criteria. The periodontal width was measured histomorphometrically and compared to the periodontal width on the contra lateral side of the same root where reattachment had taken place and with the width of normal periodontal space of neighbouring untreated teeth. The mean periodontal width for both after formation of a long junctional epithelium and reparative cementum were significantly larger than the control width, approximately 290%. This may be taken as evidence of an impaired functional adaptation of the reparative tissue compared to a reestablished or normal periodontal membrane. PMID- 7871478 TI - Quality of periodontal healing. IV: Enzyme histochemical evidence for an osteoblast origin of reparative cementum. AB - The aim of the present study was to map the distribution of healing gingival and periodontal connective tissue well as osteoblastic activity in marginal periodontal wound healing using activity of alkaline phosphatases as markers. Activity of non-specific alkaline phosphatase (NSAP) was abundant in periodontal but not in gingival connective tissue. Activity of vanadate-resistant alkaline phosphatase (VRAP) had a preferential localisation to periosteal and endosteal bone surfaces but was not detectable in cementoblasts along root surfaces. However, following spontaneous marginal healing of exposed dentine surfaces, activity of VRAP was also found on healing dentine surfaces. It was concluded that osteoblasts rather than cementoblasts form reparative cementum on exposed dentine surfaces during marginal periodontal healing. PMID- 7871479 TI - Craniomandibular disorders in children--a critical review of the literature. AB - Reports of prevalences of craniomandibular disorders (CMD) in children and adolescents differ markedly from one study to another. Therefore it is almost impossible to get a clear picture of the magnitude of the disorder in a child population. The aim of this study was to critically compare and analyse the results presented in recent publications in order to get a comprehensive view of the prevalence of CMD in children and adolescents. Fourty epidemiological studies on CMD symptomatology and headache in the age group three to 25 years were included. Eight symptoms and eight signs were chosen for further comparisons and analyses. The prevalences of these signs and symptoms were evaluated and classified according to a set of criteria, in either frequency of "greater clinical relevance" or frequency of "lesser clinical relevance". The evaluation was based on the presented examination methods, definitions and symptom criteria used in the studies. The reported frequencies for the sixteen signs and symptoms are presented graphically. The diagram clearly show great variation in the reported frequencies for most signs and symptoms. If only reported frequencies of "greater clinical relevance" are considered, these variations are less pronounced but still considerable. One major reason for this is inter- and intraindividual variation among the examiners. Another plausible and often overlooked reason is the fact that examination methods designed for adults uncritically have been applied on children without consideration of age and cognitive development of the child. PMID- 7871480 TI - Compressive fracture resistance of the marginal ridge in large Class II tunnels restored with cermet and composite resin. AB - Compressive fracture resistance of the marginal ridge was studied in large tunnel preparations, before and after restoration with cermet (Ketac Silver, ESPE), a universal hybrid composite (Superlux, DMG) and an experimental composite. Each group was represented by six tunnels in extracted upper premolars. The tunnels were prepared by the use of round burs up to size #6. Remaining ridge width was 1.5 mm and ridge height 1.7 mm in the contact area. The ridge was loaded to fracture by a rod placed perpendicular to the ridge. Generally this resulted in a shear fracture of the restoration. There was no significant reinforcement of the ridge by the cermet whereas the composites both reinforced by the same magnitude, averaging 62%. It was concluded that the ridge could be considered a "megafiller" where contact need to be preserved and contour protected against proximal and occlusal wear of the restoration. Clinically there would therefore be good reasons to save even ridge areas with very low inherent strength. Based on the present study composite resin might therefore be the filling material of choice for such tunnel preparations. PMID- 7871481 TI - Pathogenetic changes in the lung bud of mutant rats with heritable pulmonary lobation anomalies. AB - The present study aimed at investigating pathogenesis of pulmonary lobation anomalies in fpl/fpl mutant rats. Day 12-15 embryos were first examined for pulmonary lobation. Lung serial sections were then made and examined for bronchial branching and distribution of extracellular matrices (ECMs). The lung buds of both fpl/fpl embryos and their phenotypically normal fpl/+ littermates were formed as bilateral protrusion of the foregut on gestation day 12. In fpl/+ embryos, three processes appeared on the right lung bud on day 13, and fissures were completely formed by day 14. In fpl/fpl embryos, the right lung bud had no clear process on gestation day 13, and fissures were not formed on day 14 and thereafter, with the exception of incomplete separation between the cranial and middle lobes. Histological observation revealed that the right main bronchial bud of fpl/+ embryos ramified all lobar bronchial buds by gestation day 13. ECMs, a borderline between endodermal bronchial buds and surrounding mesenchyme, disappeared at the distal end of each lobar bronchial bud. By contrast, in fpl/fpl embryos, the right main bronchial bud did not ramify the middle and intermediate lobar bronchial buds at its lateral and ventral portions, but swelled on gestation day 13. It was covered with ECMs at the lateral side but not at the ventral region, from which the middle and intermediate lobar bronchial buds arose on gestation day 14. These observations suggest that altered distribution of ECMs causes branching abnormalities of the lobar bronchial buds and subsequent lobation anomalies in fpl/fpl embryos. PMID- 7871482 TI - Maternal toxicokinetics, metabolism, and embryo exposure following a teratogenic dosing regimen with 13-cis-retinoic acid (isotretinoin) in the cynomolgus monkey. AB - The maternal pharmacokinetics, metabolism, and placental transfer of 13-cis retinoic acid (isotretinoin) have been determined in the cynomolgus monkey using a dosing regimen which had been previously shown to result in retinoid-specific teratogenic effects [Hummler et al. (1990) Teratology 42:263-272]. The drug (2.5 mg/kg body weight) was administered by nasogastric intubation once a day between gestational days (GD) 16-26, and twice a day between GD 27-31. Maternal plasma kinetics were determined following dosing on GD 26 and GD 31, and placental transfer was studied following the last dose on GD 31. The plasma half life of 13 cis-retinoic acid in the monkey (13.2 h) was comparable to that in the human. The main plasma metabolite in the monkey was the 13-cis-4-oxo-retinoic acid which occurred at levels lower or comparable to those of the administered drug. During multiple dosing, this metabolite accumulated to the same degree as the parent drug. All-trans-retinoic acid was present in maternal plasma in very low concentrations (2% of 13-cis-retinoic acid). The beta-glucuronides of all-trans- and 13-cis-retinoic acid were further minor plasma metabolites. 13-cis-retinoic acid and its 4-oxo-metabolite reached the monkey embryo slowly but extensively during organogenesis and reached 24 h-AUC values of 956 and 590 ng.h/g embryo wet weight, resulting in embryo/maternal plasma concentration ratios of 0.41 and 0.33, respectively. The AUC value of all-trans-retinoic acid (316 ng.h/g) was only raised approximately 40% above the endogenous AUC level (225 ng.h/g); only at two time periods examined were the embryonic all-trans-retinoic acid concentrations above endogenous levels (at 4 h and 8 h; P < 0.01 and < 0.05, respectively; Student's t-test). The beta-glucuronides of all-trans- and 13-cis retinoic acid were not detected in the embryo. Accumulation of 13-cis-retinoic acid and the 4-oxo-metabolite during the twice-per-day dosing regimen was apparent both in maternal plasma and embryo. An interspecies comparison suggests that the half life as well as the metabolic pattern of 13-cis-retinoic acid in plasma were similar in monkey and human: 13-cis-4-oxo-retinoic acid was the main metabolite in both species and the beta-glucoronides as well as all-trans retinoic acid were minor metabolites. However, the plasma AUC values of the administered drug and particularly the 4-oxo-metabolite were found to be lower in the monkey as compared to the human.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7871483 TI - Prevalence of neural tube defects in Cape Town, South Africa. AB - The aim of the study was to document the frequency of neural tube defects (NTD) over a 20-year period in Cape Town and to determine the effects of race, gender, maternal age, parity and season of conception on the prevalence. Multiple sources of ascertainment were used, including all maternity hospital records, neurosurgical and spinal defects clinic data, as well as those from the Human Genetics Department and Fetal Abnormality Group. The prevalence rates for NTD fluctuated between 1.74 and 0.63 per 1,000 births, but showed no significant trends over the 20-year period. Prevalence rates were highest for the white population group of 2.56 per 1,000 births compared to 0.95 per 1,000 for blacks and 1.05 per 1,000 for those of mixed ancestry. The higher rates in the whites, who are of British and European extraction and belong to the more affluent section of the community, would suggest that the possible effects of nutrition and infection are overshadowed by genetic factors. There was a female preponderance for both spinal bifida (M:F ratio 0.89) and anencephaly (M:F ratio 0.67). The highest NTD rates were found at both ends of the maternal age range (< 20 years and > 35 years of age). The prevalence was highest at the extremes of birth order (1.65 and 1.58 for birth order 1 and > 7, respectively, and 0.56 and 0.45 for birth order 5 and 6, respectively). A seasonal variation occurred which differed from that reported for the Northern Hemisphere and may reflect local climatic conditions. PMID- 7871484 TI - Deaths associated with renal agenesis: a population-based study of birth prevalence, case ascertainment, and etiologic heterogeneity. AB - We report on deaths associated with renal agenesis among 211,704 consecutive births. Sources included birth and death certificates and an active birth defects surveillance system. Medical review and classification of cases were performed for 1985-1990 events. Sixty-one cases of renal agenesis were identified, and review of records was possible for 59 of the 61 cases. Of these 59 cases, 36 (61%) were confirmed, 5 (8%) were questionable, and 18 (31%) were incorrectly coded. The prevalence of confirmed cases is thus estimated at 17/100,000 births (14.2/100,000 births, excluding elective terminations and fetal deaths). Records incorrectly coded were most often those with multicystic dysplasia. Approximately one-third of cases was found by the birth defects surveillance system alone, confirming the utility of this data source for prevalence estimates. Isolated renal agenesis accounted for 44% of confirmed cases; other diagnoses included VATER association (19%), unrecognized multiple malformation syndromes (17%), exstrophy of the cloaca sequence (14%), and chromosome disorders (6%). Based on these data, prevalence rates for ICD code 753.0 and death include overascertainment of cases from erroneous coding of multicystic dysplasia and underascertainment of cases with unilateral renal agenesis associated with other malformations. Population-based ascertainment of cases by active surveillance methods and rigorous diagnostic coding standards are required to improve the accuracy of these rates. Targeted investigations of distinct subclassifications will be necessary to identify specific etiologic factors. PMID- 7871485 TI - Acardia: predictive risk factors for the co-twin's survival. AB - This study aimed to find factors in acardiac pregnancies that could be used to predict survival rates of the pump fetus. Five cases of acardia at Monash Medical Centre were found, and all case reports available in the literature from 1960 to 1991 (184 cases) were collected and analyzed. Acardia is more common in nulliparous women and in monoamniotic monochorionic pregnancy. The acardiac fetus usually has a two-vessel umbilical cord and is most likely to develop structures supplied by the lower aortic branches. Delivery is more often preterm (mean gestation = 31.1 weeks) than normal twins. The overall perinatal mortality for the pump fetus is 35% in twins and 45% in triplets. Factors associated with a statistically significant increase in perinatal mortality for the pump fetus include delivery before 32 weeks gestation, acardiacus anceps form of acardia, and the presence of arms, ears, larynx, trachea, pancreas, kidney, or small intestine in the acardiac fetus. Active intervention in these pregnancies is reasonable. PMID- 7871486 TI - In vitro embryotoxicity of the cysteine proteinase inhibitors benzyloxycarbonyl phenylalanine-alanine-diazomethane (Z-Phe-Ala-CHN2) and benzyloxycarbonyl phenylalanine-phenylalanine-diazomethane (Z-Phe-Phe-CHN2). AB - This study makes use of whole embryo culture to investigate the potential embryotoxicity of benzyloxycarbonyl-phenylalanine-alanine-diazomethane (Z-Phe-Ala CHN2) and benzyloxycarbonyl-phenylalanine-phenylalanine-diazomethane (Z-Phe-Phe CHN2), two low molecular weight, active site-directed and irreversible inhibitors of the lysosomal cysteine proteinases. Peptidyl diazomethanes are the most specific inhibitors available for lysosomal cysteine proteinases and can be hypothesized to interrupt visceral yolk sac (VYS)-mediated nutrition during early organogenesis. When added directly to the culture medium of gestational day 10-11 rat conceptuses, both compounds inhibited lysosomal cysteine proteinase activity in the VYS in a concentration-dependent fashion that correlated with the degree of embryotoxicity observed. Z-Phe-Ala-CHN2 and Z-Phe-Phe-CHN2 were also found to increase the protein content of the VYS, even though all other conceptual growth parameters decreased. This effect was dependent on the serum content of the culture medium and the exposure time. Histological examination of Z-Phe-Ala-CHN2 treated conceptuses revealed a dramatic increase in the size and number of vacuoles in the VYS endoderm epithelium, suggestive of inhibition of VYS proteolysis. At the same time, excessive cell death was observed throughout the neuroepithelium and in specific regions of the mesenchyme of the corresponding embryos. This cell death manifested morphological characteristics of apoptosis and could be detected by supravital staining with Nile Blue Sulphate. These findings provide additional evidence in support of the hypothesis that lysosomal cysteine proteinases play a critical role in VYS-mediated histiotrophic nutrition and suggest that peptidyl diazomethanes may be useful in further characterization of these enzymes. The possible direct effects of these inhibitors on embryonic cells and the relationships between interruption of VYS-mediated nutritional processes and embryonic cell death are discussed. PMID- 7871487 TI - Effects of static and time-varying (50-Hz) magnetic fields on reproduction and fetal development in rats. AB - Mated Wistar rats were chronically exposed to a static magnetic field (MF) from day 1 to day 20 of pregnancy. Flux density of the MF was 30 mTesla (mT), i.e., within the range of exposures of operators of magnetic resonance imaging (MRI) devices. For comparison with effects of this static field, a time-varying (50-Hz) MF of the same flux density was used. In both experiments, i.e., static or 50-Hz MF exposure, sham-exposed groups of dams served as controls. On day 20, the dams were sacrificed for reproductive and teratological assessment. The litters were evaluated for numbers of implantations, fetal deaths and resorptions, gross external, visceral, and skeletal malformations, and fetal weights. No adverse effects were seen in the dams during MF exposure. The mean number of living fetuses per litter was significantly decreased in the group with static MF exposure, but not the group with 50-Hz MF exposure. Further differences between the two types of field exposure were observed with respect to minor (skeletal) fetal anomalies which were increased in the 50-Hz but not the static MF group. No serious malformations were seen in any group. In both MF-exposed groups, increased skeletal ossification was found, possibly indicating an accelerated prenatal development. In a second experiment with static MF (30 mT) in which dams were exposed for the whole period of pregnancy, and postnatal growth and development of offspring were studied, the postnatal growth was significantly enhanced in offspring following their prenatal MF exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871488 TI - Behavioral teratologic effects of prenatal exposure to continuous-wave ultrasound in unanesthetized rats. AB - While there are no known risks associated with diagnostic ultrasound, uncertainty about the safety of prenatal ultrasound exposure remains. The purpose of the present experiment was to evaluate the behavioral teratogenic potential of continuous-wave (cw) ultrasound in rats, in the absence of maternal anesthesia or restraint. Pregnant CD rats, trained to remain immobile in a water-filled ultrasound exposure tank, were scanned with 3 MHz cw ultrasound at levels of 0, 2, 10, 20, or 30 W/cm2 ISPTA (spatial peak, temporal average intensity) on gestational days 4-20 for approximately 10 min/day. Offspring were examined postnatally for survival, growth, physical landmarks of development, behavioral development, and the adult functions of locomotor activity, learning and memory, and startle reactivity. No effects of prenatal ultrasound were found on maternal characteristics, offspring survival or growth, physical or behavioral landmarks of development, or adult tests of passive avoidance or startle. Effects at the highest intensity were obtained on corner and side locomotor activity and in a multiple-T water maze on measures of errors of commission and time spent finding the goal. The results showed that prenatal cw ultrasound in rats can induce effects on some postnatal neurobehavioral functions at high exposure intensities (30 W/cm2), but at lower intensities (2-20 W/cm2) no consistent evidence of neurobehavioral effects was observed. PMID- 7871490 TI - Steps to protect yourself and/or your career. PMID- 7871489 TI - Alcohol-induced brain growth restrictions (microencephaly) were not affected by concurrent exposure to cocaine during the brain growth spurt. AB - The prevalence of concomitant use of alcohol and cocaine among drug abusers has raised concern about the possible increased risk of fetal damage. The aim of this study was to assess the interactive effects of alcohol and cocaine on lethality, somatic growth, and brain growth using an animal model system. Sprague-Dawley rat pups were used as subjects. They were randomly assigned to 1 of the 9 artificially reared groups which varied with respect to the combination treatments of cocaine (0, 40, or 60 mg/kg) and alcohol (0, 3.3, or 4.5 g/kg). All artificially reared pups were given daily cocaine and alcohol treatments during a major part of the brain growth spurt period (postnatal days 4-9). An additional group of suckled control animals raised by their natural dams was included to control for artificial rearing. The results are summarized as follows: 1) Drug induced lethality was higher in cocaine-treated groups when compared with non cocaine-treated groups, and the concurrent administration of high doses of alcohol and cocaine significantly increased the mortality rate. 2) Somatic growth, in terms of body weight, was not affected by alcohol, cocaine, or the combination of both drugs using the artificial rearing technique. 3) Alcohol exposure during this brain growth spurt period significantly reduced whole brain weight, as well as forebrain, cerebellum, and brain stem weights. 4) In contrast to alcohol, cocaine failed to exert a detrimental effect on brain weight measures during this early postnatal period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871492 TI - N,N,N-trimethylsphingosine modifies aggregatory response and ATP release from platelets in whole blood. AB - We investigated the influence of N,N,N-trimethylsphingosine (TMS), a potent inhibitor of protein kinase C (PKC), on whole blood aggregation and ATP release from platelets. The preincubation with TMS at 1 microM for 2 min enhanced ATP release during arachidonic acid-induced aggregation. The ristocetin-induced agglutination was inhibited in a TMS concentration-dependent manner, which suggests that TMS may interact with the vWF receptor on platelets. TMS suppressed aggregatory response and ATP release from platelets after the addition of collagen. In contrast, the platelet aggregation induced by ADP and 12-O tetradecanoylphorbol-13-acetate (TPA) was only slightly inhibited and the ATP release was not influenced after preincubation with TMS. Our results are in contrast to previous reported data, which were obtained using PRP and washed platelets. PMID- 7871491 TI - Reduction in human neutrophil superoxide anion generation by n-3 polyunsaturated fatty acids: role of cyclooxygenase products and endothelium-derived relaxing factor. AB - Dietary supplementation with n-3 polyunsaturated acids (PUFAs) results in augumented vasorelaxation and reduction in superoxide anion generation. Augmented vasorelaxation may be mediated by enhanced generation of vasodilator prostaglandins and/or endothelium-derived relaxing factor (EDRF), now thought to be nitric oxide (NO). To determine the importance of enhanced vasodilator prostaglandins or EDRF-NO in reduction in superoxide anion generation during n-3 PUFAs intake, human polymorphonuclear leukocytes (PMNs) were incubated with n-6 PUFA arachidonic acid (AA), or n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (each 10(-7) M) for 1 hr at 37 degrees C. Parallel sets of PMNs were treated with the cyclooxygenase inhibitors indomethacin (10(-5) M), or aspirin (10(-5) M), or the EDRF-NO synthase inhibitor L-NMMA (10(-3) M) prior to incubation with PUFAs. Superoxide anion generation by PMNs was determined by measuring the superoxide dismutase (SOD) inhibitable reduction of ferricytochrome C. PMNs incubated with EPA or DHA, but not AA, demonstrated marked reduction in superoxide anion generation. This reduction in superoxide anion generation by n-3 PUFAs was abolished by treatment of PMNs with indomethacin or aspirin, but not by L-NMMA. These observations suggest that n-3 PUFAs decrease superoxide anion generation primarily by a prostaglandin-dependent pathway. PMID- 7871493 TI - Fibronectin inhibition of platelet thrombus formation in an in vivo porcine model of vascular injury. AB - Platelets adhere and aggregate in response to exposed subendothelial matrix during vascular injury. The present study examines the effect of plasma fibronectin on platelet deposition at a site of vascular injury in an in vivo porcine model. The internal carotid arteries in anesthetized Yorkshire pigs were bilaterally exposed and the distal half of each vessel stripped of endothelium. Following stripping, one in situ carotid artery preparation was filled with 0.5 mg/ml porcine plasma fibronectin and the other artery filled with vehicle solution, to serve as a control. After five minutes, 6-7 x 10(9) 111Indium labeled autologous platelets were infused via a femoral vein cannula, and carotid blood flow was re-established for 20 minutes. The vessel segments were excised and deposition of platelets determined. Vascular stripping increased platelet deposition 52-fold, as compared to unstripped vessel segments. Fibronectin pretreatment did not affect platelet deposition in control vessel segments but decreased platelet deposition by 77% in stripped vessel segments. Transmission and scanning electron microscopy indicated that reduced platelet deposition in the fibronectin treated group was due to decreased platelet aggregation rather than decreased adhesion. PMID- 7871494 TI - Characteristic effects of activated human protein C on tissue thromboplastin induced disseminated intravascular coagulation in rabbits. AB - Protein C (PC) is the zymogen of an anticoagulant serine protease and is converted to its active form (activated protein C: APC) by thrombin in the presence of thrombomodulin. APC plays an important role in regulating thrombosis and fibrinolysis by inhibiting not only blood coagulation factors Va and VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). In the present study we examined the effects of human APC on tissue thromboplastin-induced disseminated intravascular coagulation (DIC) in rabbits and compared them with those of heparin. Both APC (300-3000 U/kg) and heparin (100-300 IU/kg) inhibited the decreases in platelet count and fibrinogen level equally. APC improved the prolonged bleeding time, but heparin aggravated bleeding with potent prolongation of activated partial thromboplastin time (APTT). Furthermore, in APC-treated animals, fibrin deposition in glomeruli was less than in heparin-treated animals. This result that APC accelerated local fibrinolysis by neutralizing PAI-1. From our findings, we concluded that APC can improve both coagulation and fibrinolysis in a DIC model and should be useful for the clinical remedy of DIC without having an adverse side effect like a bleeding tendency. PMID- 7871495 TI - Dextran sulphate activation of the contact system in plasma and ascites. AB - We have previously reported on the presence of proenzymes and inhibitors of the contact system in ascitic fluid. Malignancy-related ascites was also found to contain both high and low molecular weight kininogen (HK and LK). On this basis we have studied a possible activation of the contact system in ascites. Generation of amidolytic activity towards the chromogenic substrate S-2302 after incubation with dextran sulphate (DXS), was found in ascites from patients with gastrointestinal cancer, but not in ascites from patients with benign liver disease. It is concluded that malignancy-related ascites allows contact activation to take place, while benign ascites does not. This activation process, generating bradykinin, could possibly be of relevance to the mechanism of ascites generation. Plasma samples from patients with ascites were also tested in relation to activation of the contact system. Activation was evaluated by immunoblotting, studying the disappearance of intact HK after the initiation of activation with different concentrations of DXS. In control plasma, activation took place at low concentrations of DXS (25 - 50 micrograms/ml). In plasma samples from patients with malignancy-related or benign ascites, contact activation was depressed. In some samples concentrations of DXS up to 1 mg/ml, were not able to activate the contact system at all. Concentrations of proenzymes and relevant inhibitors in the contact system, HK and total protein were also determined. We found the concentration of prekallikrein to be positively correlated with the degree of activation. Concentrations of inhibitors such as C1 inhibitor, did not show any correlation with activation. PMID- 7871496 TI - Procoagulant and profibrinolytic activities of cryopreserved human monocytes. AB - The purpose of this study was to compare the ability of fresh and cryopreserved mononuclear cells to generate thrombin, induce fibrin formation and finally resolve the fibrin formed, when exposed to plasma. Peripheral blood mononuclear cells (PBM) from 4 donors were collected by gradient centrifugation on Lymfoprep, and cryopreserved in fetal calf serum and 10% dimethyl sulfoxide. Viability was tested by exclusion of trypan blue, as well as green/red fluorescence of fluorescein-diacetate and ethidium bromide (FDA/EB). Fresh and frozen-thawed cells were seeded, stimulated with lipopolysaccharide(LPS), and exposed to a standard heparinized overlay plasma. Plasma was harvested at intervals (0-7 days). Thrombin generation and fibrin formation were measured by quantification of prothrombin fragment (F1 + 2) and fibrinopeptide A (FPA) and the fibrinolytic capacity of the cells as the amount of fibrin (ogen) degradation products (FbDP and FgDP). Recovery of cells after thawing was about 80%, and the viability of fresh and cryopreserved PBM was > 95%. Compared to fresh, frozen cells fully retained their capability of Tissue Factor synthesis, leading to prothombinase activity (F1 + 2) and fibrin formation (FPA). In contrast, the fibrinolytic capacity of frozen-thawed cells were significantly reduced. As expected there were significant variations between the donors in all the parameters measured. We conclude that cryopreservation of human blood mononuclear cells is possible with maintainance of the potential of the cells to mediate coagulation in plasma upon LPS stimulation, whereas the fibrin resolving capacity apparently is reduced by the preservation procedure. PMID- 7871497 TI - Some questions about acquired inhibitors and bleeding time. PMID- 7871498 TI - The inhibitory effect of platelets on fibrinolysis in diabetic patients. PMID- 7871499 TI - [Occupational diseases and preventive health care]. PMID- 7871500 TI - ["Pouchitis" (inflammation of the ieal reservoir)]. PMID- 7871501 TI - [Vitamins and clinical chemical tests--small things may have big consequences]. PMID- 7871502 TI - [Treatment of terminal heart failure]. AB - Heart transplantation is one treatment for terminal heart failure. To assure a good result it is important to give optimal treatment while waiting for a suitable donor organ. We review the treatment received by patients on the waiting list for heart transplantation at our hospital from 1983 to 1994. On the basis of our experience from 183 patients, we discuss the routine and intensive care of severe heart failure, as well as the practice of anticoagulation and antiarrhythmic treatment. PMID- 7871503 TI - [Hemopericardium with cardiac tamponade. Case reports from a coronary care unit]. AB - We describe three patients with cardiac tamponade who had been admitted to a coronary care unit, two because of rupture of the free wall during acute myocardial infarction and one because of proximal aortic dissection. Pericardiocentesis was performed in the coronary care unit after the diagnosis had been made by echocardiography. One of the patients with acute infarction and the one with proximal aortic dissection, who also underwent surgery, survived. We discuss various aspects of acute cardiac tamponade with hemopericardium. PMID- 7871504 TI - [Chronic cold agglutinin disease]. AB - Chronic cold agglutinin disease is an uncommon form of haemolytic anaemia. Traditionally the "idiopatic" form and the "secondary" form (seen in some cases of malignant lymphoma) have been regarded as two clearly different entities. We describe three patients with chronic cold agglutinin disease in a population of 100,000. They had been previously diagnosed as having idiopatic autoimmune haemolytic anaemia, but further investigations revealed lymphoproliferative bone marrow disease in all three cases. We discuss some pathogenetic features of cold agglutinin disease on the basis of our observations and the available literature. In conclusion, this disease represents a spectrum of clonal lymphoproliferative disorders rather than separate primary and secondary forms. The therapeutic principles are discussed. Corticosteroids should usually not be used to treat this disease. PMID- 7871505 TI - [Induced sputum. Indication for examination in Pneumocystis carinii pneumonia?]. AB - Induced sputum is a simple, rapid, and non-invasive technique for detection of Pneumocystis carinii in patients with Pneumocystis carinii pneumonia. In this study 31 patients were examined both with induced sputum and bronchoalveolar lavage. P. carinii was found in 24 patients. In 68% of the samples obtained by the induced sputum method the microorganism was found after Giemsa or methenamine silver staining. In 32% the diagnosis was established in the lavage fluid only. Induced sputum is indicated in moderate cases of P. carinii infection. Bronchoalveolar lavage has to be performed in suspected cases where staining of induced sputum is negative and when coinfection with other microbial agents is suspected. PMID- 7871506 TI - [Bleeding ulcer disease. Its course before and after endoscopic sclerotherapy]. AB - The article presents a retrospective assessment of the outcome of bleeding gastrointestinal ulcer disease before and after the advent of endoscopic therapy. In 1985, 97 patients were urgently admitted to our county hospital with ventricular or duodenal ulcers. In 1992, 92 such patients were admitted. No patients received endoscopic therapy in 1985, while 15 patients received endoscopic injections with epinephrine combined with a sclerosant in 1992. 15 patients underwent urgent surgery in 1985 compared with seven patients in 1992. We conclude that endoscopic therapy for bleeding peptic ulceration has decreased the need for urgent surgery by 50%. PMID- 7871507 TI - [Fat-soluble vitamins in clinical practice]. AB - The identification of fat-soluble vitamins at the beginning of this century had a major impact on human health. The classical deficiency symptoms could be treated with effective means. After a period of rather low interest in fat-soluble vitamins, we are now in the midst of a new wave of research on these vitamins, with a large number of reports in influential international journals. It has been demonstrated that the fat-soluble vitamins have many more functions than previously known, and suboptimal status has been linked to several diseases. In this review, we describe these new aspects of the fat-soluble vitamins A, D, E and K. PMID- 7871508 TI - [Time utilization in the preparation of medical records]. AB - The time available for preparing a medical record may be of importance for the resulting quality. We studied the records of 166 patients admitted to a medical department during a fortnight. 24 doctors registered the time spent on history taking, clinical examination and emergency treatment, paper work and other patient-associated tasks. The doctors received a mean of seven patients each, spending a mean of 53 (range 20-120) minutes in all. The mean time spent on clinical examination was 27 minutes, on paper work 18 minutes and on other tasks 11 minutes. Time of the day or age of the patient did not influence the time spent on the tasks. Only rarely (7%) did the doctor experience shortage of time. PMID- 7871509 TI - [The medical record--content, interpretation and quality. Study of 100 medical records from a department of internal medicine]. AB - An evaluation of the primary medical records of 100 patients admitted to a medical department showed that several elements in the journal often had been left out. Therefore all doctors working in the department were asked for their opinion of the necessity for each of the elements in a journal. A comparison of these doctors' opinions with our registrations indicated that the actual "shortening" of the journals was probably a result of choice rather than mere chance. Despite a considerable amount of work trying to establish relevant criteria, we did not succeed in developing a reliable method for measuring the quality of the medical record. The journals recorded at night were significantly shorter than those recorded during the day. A follow-up note (or discharge of the patient within one day), was found in 80% of the journals. Quality standards of the medical record are lacking and should be developed. PMID- 7871510 TI - [Reporting occupational disease. A system ready for revision]. AB - The article reviews the system of reporting occupational disease and the reporting pattern over the last ten years. The available information seems to indicate a very low reported incidence of occupational disease. Possible reasons are given. There seems to be a need to simplify our present system and make it more user-friendly. There is also a general need to inform and motivate various user groups, especially general practitioners. In addition, greater collaboration between occupational and public health services may help to increase the reporting of occupational disease in Norway. PMID- 7871511 TI - [The Liland case. Medicolegal aspects]. AB - In 1970 a 39 year-old man was sentenced to lifelong imprisonment (21 years) plus ten years of preventive detention for having killed two persons with an axe on December 22, 1969. The sentence was based upon circumstantial evidence and medicolegal reports which suggested that these persons had been killed on December 22 or early December 23. The accused had an unquestionable alibi for December 23. Re-examination of the medicolegal reports 24 years after the verdict demonstrated that the killings could not have taken place on December 22. Therefore, in a new trial on November 21, 1994, the accused was fully acquitted. Measures by which similar medicolegal errors can be prevented are discussed. PMID- 7871512 TI - [Education in internal medicine and the American health reform in Honolulu]. PMID- 7871513 TI - [Social class in health statistics and research]. PMID- 7871514 TI - [Prevention of cardiovascular diseases--easier to say than to do]. PMID- 7871515 TI - [Multifactor evaluation of the risk of cardiovascular disease]. PMID- 7871516 TI - [Active euthanasia should not be performed by physicians]. PMID- 7871517 TI - [Harassment of physicians]. PMID- 7871518 TI - [A new lower class of young colleagues in Norwegian health care?]. PMID- 7871519 TI - [Testing the local health care measures]. PMID- 7871520 TI - TCC not TTC: the integrity of the HLA nucleotide sequence database. PMID- 7871521 TI - Analysis of HLA-B*44 alleles encoded on extended HLA haplotypes by direct automated sequencing. AB - We developed a PCR-based approach to sequence exons 2 and 3 of HLA-B44 alleles from genomic DNA. We applied this method to determine the B44 alleles encoded on extended HLA-A, B, DRB1, DQB1 haplotypes and the degree of mismatching for B44 alleles among marrow transplant patients and their unrelated donors (URD). A total of 81 samples was studied and included 38 patients, 42 donors and the cell "FMB"; the 80 clinical samples were comprised of 8 unpaired patients, 12 unpaired donors, and 30 URD-recipient pairs. Three alleles encoding B44 were identified, B*4402 (N = 51), 4403 (N = 32) and a new allele designated B*44KB and named B*4405 (N = 4). Of the 27 patients for whom family study was available, there were 13 different B*4402, 7 different B*4403 and 2 new B*4405 haplotypes. HLA-A2, Cw*0501, B*4402, DRB1*0401, DQB1*0301 (n = 2); A2, Cw*0501, B*4402, DRB1*1501, DRB5*0101, DQB1*0602 (n = 2); and HLA-A29, Cw*1601, B*4403, DRB1*0701, DQB1*0201 (n = 5) comprised the most common patient haplotypes. Of 30 URD-recipient transplant pairs studied, 27 were HLA-A, B serologically matched and DRB1, DRB3, DRB5, DQB1 allele matched, and 3 pairs were DRB1-mismatched. All B44 allele mismatching (N = 3) occurred among the 27 matched pairs. The novel B*4402-variant sequence, HLA-B*4405, was identified in 4 individuals, and in each case was associated with an HLA-B44, Cw*02022, DRB1*0101, DQB1*0501 haplotype. HLA-B*4405 and B*4402 are identical in exon 2; in exon 3 however, B*4405 encodes T instead of G at nucleotide position 75 which translates to a substitution of tyrosine for aspartic acid at codon 116.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871522 TI - A small test of a sequence-based typing method: definition of the B*1520 allele. AB - Santamaria et al. (Human Immunology 1993 37: 39-50) describe a method of sequence based typing (SBT) for HLA-A, B and C alleles said to give "unambiguous typing of any sample, heterozygous or homozygous, without requiring additional typing information". From SBT analysis, which involves determination of partial sequences of mixed alleles, these investigators reported that cell lines KT17 (HLA-B35,62) and OLGA (HLA-B62) from the reference panel of the 10th International Histocompatibility Workshop express novel variants of HLA-B15 (B1501-MN6) and HLA-B35 (B3501-MN7) respectively. To study further the novel alleles, we cloned and sequenced full-length HLA-B cDNA clones isolated from the KT17 and OLGA cell lines. We find that KT17 expresses B*3501, as assigned by SBT, and B*1501, the common allele encoding the B62 antigen. We were unable to confirm that KT17 expresses the novel B1501-MN6 variant identified by SBT. For OLGA our analysis confirms the partial sequences obtained by SBT. Thus OLGA expresses B*1501 and a novel HLA-B allele. The complete sequence of the latter shows it is a hybrid having exons 1 and 2 in common with B*1501 and other B15 subtypes and exons 3-7 in common with B*3501 and related molecules including B*5301 and B*5801. The novel allele has been designated B*1520 because of its sequence similarity with the B15 group; furthermore, serological analysis shows that the B*1520 product does not express epitopes in common with either B35, B53 or B58. The B*1520 heavy chain has a similar isoelectric point to A*3101; B*1520 was undetected by previous applications of isoelectric focusing because B*1520 and A31 are both expressed by OLGA. In conclusion, HLA-B typing of two cell lines by cDNA cloning and sequencing gives concordant results with SBT for three of the four alleles. The cause of the discrepancy for the fourth allele is unknown, however, this finding indicates that the novel HLA-A, B and C sequences emerging from SBT studies need independent verification. PMID- 7871523 TI - HLA class II alleles confer susceptibility to recurrent fetal losses in Danish women. AB - HLA-DR and -DQ typings were performed by a combination of RFLP and PCR-SSP techniques in 234 Danish women with at least three consecutive unexplained fetal losses (recurrent fetal losses) and 360 controls and the DRB1, DQA1 and DQB1 alleles were deduced. In the total group of patients, the frequency of no DRB1 DQA1-DQB1 haplotype was significantly increased compared with controls. In the subgroup of 97 women with four or more fetal losses (multiple fetal loss group), the frequency of women carrying the DRB1*0101, DQA1*0101, DQB1*0501; DRB1*0102, DQA1*0101, DQB1*0501 and DRB1*0103, DQA1*0101, DQB1*0501 haplotypes or the DRB1*0301, DQA1*0501, DQB1*0201 haplotype were significantly increased compared with controls (RR = 2.1; pc < 0.05 with regard to former three haplotypes combined and RR = 2.2; pc < 0.05 for the latter). The frequency of women with at least one of the four haplotypes was significantly (p < 0.002) increased with the number of previous fetal losses in the women's history. Analysis of the DQA1 and DQB1 phenotypes in women with at least four fetal losses showed that DQA1*0501 and DQB1*0501 were increased compared with controls (RR = 1.9; pc < 0.05 and RR = 2.2; pc < 0.025, respectively). Analysis of DRB1-DQA1-DQB1/DRB1-DQA1-DQB1 genotypes suggested that genotypes comprising both DQA1*0501 and DQB1*0501 alleles (in trans) exhibited a higher RR for experiencing at least four fetal losses (RR = 3.4, p = 0.002) than each of the alleles did alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871524 TI - Insulin-dependent diabetes mellitus and the major histocompatibility complex peptide transporters TAP1 and TAP2: no association in a population with a high disease incidence. AB - Although many studies have established an association between insulin-dependent diabetes mellitus (IDDM) and the class II region of the human major histocompatibility complex (MHC), it has been difficult to assign susceptibility to a single locus. Recently, two antigen-processing genes, TAP1 and TAP2, have been identified within the region. Previous studies have reached conflicting conclusions as to the role of these genes in IDDM; it is uncertain whether an increased frequency of the allele TAP2A and a concomitant decrease in TAP2B are independent disease associations or secondary to linkage disequilibrium (LD) between TAP2A and HLA-DR3. To further investigate this question, we have characterized TAP1 and TAP2 alleles in 129 IDDM patients from Sardinia, a population with limited genetic heterogeneity and a high disease incidence. When compared to 90 random controls, the only significant difference was a decrease in the minor allele TAP2C in patients. However, when HLA-DR and -DQ matched controls were compared, this difference disappeared. Further analysis suggested that TAP2C was in LD with HLA-DRB1*1401 and subtypes of HLA-DRB1*11, alleles which were not observed in the IDDM population. LD was also observed between other TAP and HLA DR alleles, in particular between TAP2A and HLA-DR3 in both patients and controls. Our data supports the conclusion that there is no primary association between TAP2 alleles and IDDM, and that previously reported associations may be due to LD with other class II loci. PMID- 7871525 TI - PCR-RFLP-based DQA1 typing of rhesus monkeys: sequence analysis of a new allele. AB - In spite of the widespread use of rhesus monkeys (Macaca mulatta) in biomedical research, MHC typing of this species is not yet routine. Since suitable antibodies are lacking, serological typing of Mamu-DQA1 is not feasible. We developed a typing protocol for MhcMamu-DQA1 from published sequences of the second exon of Mamu-DQA1. This protocol is based on the amplification of the second exon of Mamu-DQA1 with one specific primer pair followed by a "diagnostic" digestion of the PCR products with, at most, 5 different restriction endonucleases. This modified PCR-RFLP permits the rapid identification of 11 out of 13 Mamu-DQA1 alleles in homozygous and heterozygous combinations. The protocol was validated by cloning and sequencing the PCR-products of several animals of different geographic origin. In addition, an as yet unknown allele was detected by PCR-RFLP and was subsequently cloned and its nucleotide sequence determined. All examined sequences except the new allele were identical to those previously published. Therefore, we assume that many of the Mamu-DQA1 alleles of rhesus monkeys have been identified molecularly and that the typing technique presented here can reliably identify Mamu-DQA1 alleles. PMID- 7871526 TI - HLA-DQA1, -DQB1 and -DRB1 genotyping in Japanese pemphigus vulgaris patients by the PCR-RFLP method. AB - We performed HLA-DQA1, -DQB1 and -DRB1 genotyping using the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method for 32 Japanese pemphigus vulgaris (PV) patients. There was a significant association of either DQB1*0503 or DRB1*1405 with PV, and a negative association of either DQA1*0103 or DQB1*0601 with PV was found. Since the DQB1*0503+ patients had various DR14 related alleles, we concluded that the association with DQB1 is primary and that the association with DRB1 is simply due to linkage disequilibrium between the DQ and DR genes. These results may indicate that specific HLA class II antigens confer the susceptibility to PV among Japanese. PMID- 7871527 TI - Sequencing of a novel functional HLA-B44 subtype differing in two residues in the alpha 2 domain. PMID- 7871528 TI - Correct sequence of the A*3001 allele obtained by PCR-SSP typing and automated nucleotide sequencing. PMID- 7871529 TI - HLA class I alleles of LCL 721 and 174 x CEM.T2 (T2). PMID- 7871530 TI - HLA-B*5105, a newly identified B51 IEF variant. PMID- 7871531 TI - Ultrastructural characterization of normal and abnormal chondrogenesis in micromass rat embryo limb bud cell cultures. AB - Inhibition of chondrogenesis in limb bud cell micromass cultures has been proposed as a short-term teratogen detection test. Validation studies were performed by testing large series of reference compounds and comparing their teratogenic potential with their ability to inhibit chondrogenesis; however, there are few reports describing the histological and ultrastructural changes associated with inhibition of chondrogenesis in vitro. The objective of this study was to provide a qualitative description of the histological and ultrastructural alterations induced by three chondrogenesis inhibitors: retinoic acid (RA) and 6-aminonicotinamide (6AN), two teratogens, and doxylamine succinate (DS), a nonteratogen compound. In addition, in order to have a basis for the interpretation of the morphological alterations induced by the test compounds, the histological and ultrastructural changes which occur during the time course of chondrogenesis in control cultures were described and compared with those in rat embryo limb buds. We found that RA at 0.5 micrograms/ml led to a marked decrease in the number and size of cartilaginous foci; most cells lacked morphological signs of differentiation but their ability to proliferate was unaffected. At concentrations of 2 micrograms/ml and more, 6AN delayed cell proliferation, reduced staining of the extracellular matrix, and induced the formation of endoplasmic cisternae. DS at 50 micrograms/ml affected both differentiation and proliferation; pigment deposits were observed in chondrocytes, suggesting phospholipid metabolism disorders. In conclusion, this study showed that inhibition of chondrogenesis in this simple cell culture system can be associated with different types of histological and ultrastructural alterations. Examination of these alterations can provide useful information about the teratogenic potential of tested compounds and their mechanism of action. PMID- 7871532 TI - Metabolism of 2-acetylaminofluorene by hepatocytes isolated from rainbow trout. AB - The metabolism of 2-acetyl-[9-14C]aminofluorene (AAF) by hepatocytes isolated from rainbow trout (Oncorhynchus mykiss), Shasta strain, was investigated in order to assess the competing activation and detoxification pathways which may explain the resistance of this species and strain to the initiation of carcinogenesis by this model carcinogenic aromatic amide. Freshly isolated hepatocytes (per milliliter: 1.0 mg dry wt; 1.5 (10(6)) hepatocytes) incubated with 65 microM AAF for 4 hr converted 15.4 nmol AAF to metabolites, including 7.8 nmol of water-soluble compounds. AAF-derived radioactivity extracted from the incubation mixtures, before and after hydrolysis by beta-glucuronidase and arylsulfatase, was analyzed by reversed-phase HPLC. The metabolite profile following incubation of hepatocytes with 6.5 microM AAF for 4 hr included (as percentage of total metabolites); 7-OH-AAF, 5-/8-/9-OH-AAF and 2-aminofluorene (AF) (17, 2.4, and 2.7%, respectively); conjugates of these respective primary metabolites (39, 9, and 4%, respectively). Glucuronides amounted to 49% of the total metabolites. N-OH-AAF and its conjugates always amounted to < 1% of total metabolites. The relative amount of (unconjugated) AF increased considerably (to 26%) following incubation of hepatocytes with 65 microM AAF, with a corresponding decrease in the total amount of glucuronides formed. Following incubation with 65 microM AAF, 1.6% of AAF metabolites was covalently bound to macromolecules, giving a ratio of covalently bound derivatives to detoxification products of 0.028. These data are consistent with the hypothesis that rainbow trout are resistant to AAF-induced hepatocarcinogenesis, in part, because trout liver efficiently detoxifies AAF and forms only relatively small amounts of active intermediates capable of binding to macromolecules, including DNA. PMID- 7871533 TI - Dose-response relationships of tissue distribution and induction of CYP1A1 and CYP1A2 enzymatic activities following acute exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) in mice. AB - Tissue disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to be dose-dependent in rats. However, no reported studies in mice have demonstrated dose- and time-dependent distribution of TCDD and the potential sensitivities of target tissues to enzyme induction. The objectives of this study were to determine in mice the effects of dose (0, 0.1, 1, or 10 micrograms [3H]TCDD/kg) and time (7, 14, 21, and 35 days posttreatment) on tissue distribution (18 tissues) and enzyme induction (CYP1A1 in liver, skin, and lung and CYP1A2 in liver). Distribution of TCDD-derived radioactivity in all tissues was dose- and time-dependent with nonlinear distribution. Liver-to-adipose tissue concentration ratios range from 0.6 to 3.1 (low to high dose at Day 7) demonstrating a dose-dependent shift in the disposition of TCDD. In contrast to liver, relative concentrations of percentage dose/g and percentage dose/total tissue decreased with increasing doses in all other tissues. At Day 7 and lowest dose, all tissues contained < 3% dose/g except for thyroid, adrenals, skin, liver, and adipose tissue which had 3, 6, 6, 15, and 24% dose/g, respectively. Induction of EROD activity, a marker for CYP1A1, was dose-dependent in liver, lung, and skin but did not parallel tissue concentrations of TCDD. At the highest dose, fold induction of EROD activity was two times greater in lung than liver, while the concentration in liver was 100 times greater than that in lung. Fold inductions of EROD activity in liver and skin were similar but the concentration was 20 times greater in liver than that in skin. Induction of hepatic acetanilide 4-hydroxylase (ACOH) activity, a CYP1A2 marker, was dose-dependent. Results of the present study demonstrated dose and time dependency in tissue distribution and induction of CYP1A1 and CYP1A2 as well as tissue sensitivities for enzyme induction in the female B6C3F1 mouse. These results provide important considerations for high- to low-dose extrapolations in risk assessments and use of sensitive markers of enzyme induction as surrogates for estimating exposure and in predicting risk. PMID- 7871534 TI - Behavioral, histological, and neurochemical effects of nickel (II) on the rat olfactory system. AB - Experimentally, inorganic, sulfated nickel compounds (Ni2+) have been shown to produce histological lesions in the nasal mucosa of rats, more specifically, atrophy of the olfactory epithelium. The present project was designed to assess the effects of inhalation of nickel sulfate hexahydrate on behavioral, histological, and neurochemical aspects of the olfactory system. Male Long-Evans rats were exposed to either background air (control) or 635 micrograms Ni/m3 for 16 consecutive days, 6 hr/day. Exposure resulted in selective lesions to the olfactory epithelium. The number of bipolar sensory receptor cells was slightly reduced and there was a significant decrease in the thickness of the olfactory epithelium. This was due primarily to a significant loss of the sustentacular cell population, with a thinning of the apical cytoplasm, concomitant with a reduction in the number of microvilli at the surface of these cells. Significant decreases in carnosine level, consistent with the nickel sulfate exposure, were observed. However, there were no changes in olfactory function as measured by either absolute threshold or two-oder discrimination tasks. PMID- 7871535 TI - Toxic interactions between fungicides that inhibit ergosterol biosynthesis and phosphorothioate insecticides in the male rat and bobwhite quail (Colinus virginianus). AB - The potential for toxic interactions between ergosterol biosynthesis-inhibiting fungicides (EBIFs), used in U.S. agriculture or clinically, and phosphorothioate insecticides was assessed in adult male rats and adult male bobwhite quail (Colinus virginianus) by measuring inhibition of plasma butyryl cholinesterase (BChE) following fungicide and insecticide treatment. Male Sprague-Dawley rats (300 g) were administered corn oil or the following EBIFs: propiconazole (400 mg/kg/day), vinclozolin (400 mg/kg/day), clotrimazole (100 mg/kg/day), or ketoconazole (100 mg/kg/day) for 3 days by oral gavage. Forty-eight hours following the final dose, a single bolus of parathion (0.4 mg/kg in corn oil) or malathion (150 mg/kg in corn oil) or corn oil alone was given po. The rats were terminated 12 hr following parathion or 4 hr following malathion dosing. Significant (p < 0.05) inhibition of BChE was observed with parathion and malathion only following clotrimazole treatment. In contrast, when a similar experiment was performed in bobwhite quail dosed with 12 mg/kg malathion following EBIF treatment, significant BChE inhibition was observed following treatment with vinclozolin or ketoconazole, but not with propiconazole or clotrimazole. Induction of cytochrome P450 in rat and quail liver by EBIFs was accompanied by enhanced oxidative desulfuration of malathion, parathion, and diazinon to toxic oxon products. Increased detoxication via oxidative dearylation/esterolytic clevage also occurred. However, while enhanced acute in vivo insecticide toxicity was observed in both species with a number of EBIF phosphorothioate combinations, EBIF-induced oxidative activation of phosphorothioates by liver microsomes in vitro was not a good predictor of this effect. PMID- 7871536 TI - Sensitivity to cadmium-induced genotoxicity in rat testicular cells is associated with minimal expression of the metallothionein gene. AB - Cadmium is a carcinogenic metal. Although the mechanism of tumor induction is unknown, DNA/metal interactions may be involved. Metallothionein can protect against cadmium toxicity in our previous work it was shown to reduce cadmium genotoxicity in cultured cells. To extend these results, the genotoxicity of cadmium was studied in R2C cells, a rat testicular Leydig cell line. The R2C cells were very sensitive to cadmium-induced single-strand DNA damage (SSD), as measured by alkaline elution. SSD occurred in R2C cells after treatment with 25 and 50 microM CdCl2 for 2 hr. Prior work showed other cells required much higher levels of cadmium (approximately 500 microM) to induce genotoxicity. The genotoxic levels of cadmium (25-50 microM) were not cytotoxic in R2C cells as assessed by a metabolic activity (MTT) assay. Pretreatment of R2C cells with a low cadmium dose (2 microM, 24 hr) had no effect on cadmium-induced SSD, in contrast to prior work in other cells where such pretreatments reduced SSD through metallothionein gene activation. In fact, cadmium or zinc treatments resulted in little or no increase in metallothionein gene expression in R2C cells as determined by Northern blot analysis for metallothionein mRNA using cDNA or oligonucleotide probes and radioimmunoassay for metallothionein protein production. Basal metallothionein mRNA was essentially nondetectable. Induction of a cadmium-binding protein in R2C cells did occur, as determined by Cd-heme assay, but did not induce tolerance to SSD. In vivo, the Leydig cell is a target for cadmium carcinogenicity and its cadmium-binding protein is thought not to be a true metallothionein. These results indicate that R2C cells are sensitive to cadmium-induced genotoxicity and that this sensitivity is associated with minimal expression of the metallothionein gene. PMID- 7871537 TI - Chloroethylene mixtures: pharmacokinetic modeling and in vitro metabolism of vinyl chloride, trichloroethylene, and trans-1,2-dichloroethylene in rat. AB - Environmental and occupational exposures are typically to mixtures of chemicals, although most toxicity information is for individual compounds. Interactions between chemicals may involve pharmacokinetic and/or pharmacodynamic effects resulting in modulation of toxicity. Therefore, physiologically based pharmacokinetic modeling has been used to analyze data describing the metabolism of vinyl chloride (VC) and trichloroethylene (TCE) mixtures in rats. A single saturable pathway was modeled, representing cytochrome P450 2E1. This was partially validated using preexposure to trans-1,2-dichloroethylene (tDCE) which virtually eliminated in vivo metabolism of both VC and TCE at low concentrations. Microsomes from tDCE-exposed animals showed inhibition of metabolism of P450 2E1 substrates (chlorzoxazone, p-nitrophenol, and TCE) and no effect on 7 ethoxycoumarin deethylation. Studies with liver microsomes from VC-exposed animals found that neither suicide inhibition nor induction occurred during 6-hr exposures to high concentrations. Therefore, these effects were not modeled. Modeling of mixtures of VC and TCE was successful only using competitive inhibition, as might be predicted for cytochrome P450 2E1 substrates, and not uncompetitive or noncompetitive inhibition. These results were further confirmed by determining the depletion of glutathione due to VC metabolism. The validation of a detailed model for the inhibition kinetics of metabolism of these two compounds permits better understanding of the implications of coexposures for toxicity. It is notable that competitive inhibition only becomes significant at relatively high concentrations (tens of ppm), while at typical low environmental concentrations (ppb), absorption is perfusion limited and enzyme is in excess so that the chemicals will be metabolized independently. PMID- 7871538 TI - Hamster Leydig cells are less sensitive to ethane dimethanesulfonate when compared to rat Leydig cells both in vivo and in vitro. AB - It has been reported that ethane dimethanesulfonate (EDS) is a Leydig cell toxicant that affects rats and hamsters (Kerr et al., 1987), while, in contrast, the Leydig cells of mice are relatively insensitive to the toxicant. In the rat, there is a rapid decline in levels of testosterone (T) within hours after EDS administration. However, T production, spermiogenesis, and fertility are restored within a few weeks as new Leydig cells are formed from undifferentiated cells in the interstitium of the testis. In an earlier study, we found, as expected, that ejaculated sperm counts (ESCs) reached a nadir 10 days after adult rats were dosed with EDS at 65 mg/kg ip along with serum and testicular T, testis and seminal vesicle weights, and in vitro T production, while, in contrast, EDS at 65 mg/kg had no effect on these endpoints in the Syrian hamster (Gray et al., 1992). In the current study, when EDS was administered to 6, 12, and 18 month old hamsters at 100 mg/kg, it produced subtle effects on serum T and sex accessory gland weights, while dramatic effects were seen in similarly exposed rats. In addition, when testes were examined by light microscopy all treated rats displayed severely reduced Leydig cell numbers, while, in contrast, only one third of the EDS-treated hamsters were affected, having moderately reduced Leydig cell numbers. In support of the histological data, 3 beta-HSD enzyme activity was reduced by 99% of control in EDS-treated rats, but it was reduced by only 35% of control in EDS-treated hamsters. An in vitro analysis of the effects of EDS on LH stimulated T production by quartered testes demonstrated that the hamster testis was less sensitive to the direct effects of EDS than the rat testis. The IC50 after 3 hr in culture was greater than 1800 micrograms EDS/ml for the hamster quarter testes, while the IC50 for the rat quarter testes was 320 micrograms EDS/ml. In summary, these results demonstrate in vivo and in vitro that Leydig cells of hamsters are less sensitive to EDS than those of the adult rat. PMID- 7871539 TI - Gender-related differences in susceptibility to acetaminophen-induced protein arylation and nephrotoxicity in the CD-1 mouse. AB - Acetaminophen (APAP) is a commonly used analgesic and antipyretic agent which, in high doses, causes liver and kidney necrosis in man and animals. Damage in both target organs is greatly dependent upon biotransformation. However, in the CD1 mouse only males exhibit cytochrome P450-dependent nephrotoxicity and selective protein covalent binding. The lack of renal toxicity in female mice may reflect the androgen dependence of renal CYP2E1. To study this, female mice were pretreated with testosterone propionate and then challenged 6 days later with APAP. Groups of control males and females were similarly challenged with APAP for comparison. All groups exhibited hepatotoxicity after APAP with similar glutathione (GSH) depletion, covalent binding, centrilobular necrosis, and elevation of plasma sorbitol dehydrogenase activity. By contrast, APAP-induced nephrotoxicity occurred only in males and in the females pretreated with testosterone. No nephrotoxicity was evident in APAP-challenged control females. The selective pattern of hepatic and renal protein arylation previously reported for male mice was similarly observed in testosterone-pretreated female mice. Western blot analysis of microsomes showed that testosterone increased renal CYP2E1 levels without altering hepatic CYP2E1. Testosterone pretreatment, in vivo, also resulted in increased activation of APAP in vitro in kidney microsomes with no effect on the in vitro activation of APAP in liver microsomes. These data suggest that APAP-mediated GSH depletion, covalent binding, and toxicity in the kidneys of testosterone-pretreated females results from increased APAP activation by the testosterone-induced renal CYP2E1. This further suggests that renal, rather than hepatic, biotransformation of APAP to a toxic electrophile is central to APAP-induced nephrotoxicity in the mouse. PMID- 7871540 TI - Evaluation of liver toxicological effects induced by polyalkylcyanoacrylate nanoparticles. AB - Intravenous administration of drug-loaded polyalkylcyanoacrylate (PACA) nanoparticles is followed by a rapid uptake by the tissues of the reticuloendothelial system, mainly the liver. Nevertheless, it is so far unknown whether chronic administration of nanoparticles can lead to damage to the liver cells. We have studied the subacute toxicological effects of these drug carriers in a rat in vivo/ex vivo model. Nanoparticles were administered intravenously at a total dose of 200 mg/kg for 14 days (10 individual doses of 20 mg/kg). Hepatocytes were then isolated. Levels of alpha 1-acid glycoprotein secretion increased while albumin secretion decreased in hepatocytes from rats treated with PACA nanoparticles. In addition, glucose production due to the fructose metabolism was lowered. Treated rats induced a temporary increase and hyposialyation of serum alpha 1-acid glycoprotein. These effects were reversible 15 days after the treatment was concluded. Finally, the involvement of Kupffer cells and polymer degradation products was studied in vitro. Modifications of hepatocyte protein synthesis related to the treatments were only observed when direct contact between nanoparticles and hepatocytes existed. Kupffer cells and polymer degradation products did not mediate the hepatocyte response to nanoparticles in vitro. In conclusion, modifications in hepatic function after chronic administration of PACA nanoparticles have been detected by the use of very sensitive models for detecting hepatoxicity. These effects were, however, found to be reversible when the treatment was stopped. PMID- 7871541 TI - Diverse mechanisms of calcium mobilization by peroxisome proliferators in rat hepatocytes. AB - The ability of six peroxisome proliferators to modulate Ca2+ homeostasis was studied in freshly isolated rat hepatocytes. Clofibrate and bifonazole (0.5 mM) caused a transient increase in cytosolic-free Ca2+ concentration ([Ca2+]i) by releasing the intracellular inositol 1,4,5-trisphosphate-sensitive Ca2+ pool. However, the mobilization of this pool by clofibrate was only transient; a subsequent exposure of the cells to the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin resulted in a second release of the same Ca2+ store, indicating that this pool could refill from the cytosol, independently of extracellular Ca2+. By contrast, bifonazole-exposed hepatocytes no longer responded to a stimulation by thapsigargin. Bifonazole also strongly inhibited Ca2+ influx. Ciprofibrate and nafenopin (0.5 mM) produced increases in [Ca2+]i that were sustained, even in the absence of extracellular Ca2+. The [Ca2+]i response was not due to release of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool and was not inhibited by prior treatment with the protonophore carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone, but was slightly antagonized by prior exposure to the Ca2+ ionophore ionomycin. Pretreating the cells with nafenopin completely abolished the response elicited by ciprofibrate, and vice versa. By contrast to the other peroxisome proliferators, WY-14,643 and bezafibrate (1 mM) increased cytosolic free Ca2+ only by approximately 30 nM. In conclusion, the structurally diverse peroxisome proliferators tested in this study all produced changes in [Ca2+]i in hepatocytes but through the redistribution of different internal Ca2+ pools. Further studies are needed to determine whether any of the observed Ca2+ changes have a role in the pleiotropic effects elicited by peroxisome proliferators. PMID- 7871542 TI - Biochemical and functional analysis of rat bronchoalveolar macrophages containing chemically induced phospholipid inclusions. AB - Cationic amphiphilic drugs (CADs) are structurally characterized by hydrophobic ring structures and hydrophilic side chains. Studies have demonstrated that repeated administration of CADs to experimental animals and humans may induce phospholipid (PL) accumulation within the cells of various tissues. The immunomodulatory azaspiranes are novel CADs with beneficial effects in a number of animal models of autoimmune disease and transplantation. Although the mechanism of action of these compounds is unclear, efficacy in all of the disease models is accompanied by the generation of suppressor cell (SC) activity in various lymphoid organs. SK&F 105685 (N,N-dimethyl-8,8-dipropyl-2 azaspiro[4,5]decane-2-propanamine+ ++ hydrochloride) and two analogs, SK&F 106615 and SK&F 103811, were compared with chlorphentermine and chloroquine for their ability to induce PL accumulation and SC activity. Oral administration of SK&F 105685 and SK&F 106615 caused PL accumulation in bronchoalveolar lavage macrophages (AM) but to a far lesser extent (three- to fivefold) than chlorphentermine. Neither the immunologically unreactive azaspirane SK&F 103811 nor chloroquine affected PL levels. AM from rats treated with SK&F 105685 or SK&F 106615 expressed more potent SC activity than chlorphentermine. Thus, SC activity did not correlate with the extent of PL accumulation. Neither SK&F 103811 nor chloroquine induced SC activity. AM from SK&F 105685-treated rats had an enhanced ability to kill the opportunistic pathogen Candida albicans in vitro indicating that there was no impairment of macrophage-dependent host defense mechanisms. PMID- 7871543 TI - Pharmacokinetic modeling of 2,4-dichlorophenoxyacetic acid (2,4-D) in rat and in rabbit brain following single dose administration. AB - A physiologically based pharmacokinetic (PBPK) model has been developed to describe the kinetics of organic anions in the central nervous system using 2,4 dichlorophenoxyacetic acid (2,4-D) as a model compound. The model consists of brain, body, venous, and arterial compartments. The brain compartment is subdivided into brain plasma, brain tissue and cerebrospinal fluid (CSF). Brain uptake is membrane-limited via a blood-brain barrier with saturable clearance from the CSF into the venous blood by the choroid plexus. The body has both a central and a deep compartment with saturable renal clearance from the central compartment. The model was used to examine venous plasma time course curves with experimental data from rats given 2,4-D by i.v. (5 or 90 mg/kg) or by oral ingestion (10, 50, or 150 mg/kg). The model was then extended to examine studies in which rabbit plasma, brain, and CSF concentrations were measured at 2 h after i.p. injection (40 mg/kg). In the rat, elimination was saturable (Vmax2 = 3.45 mg/h; Km2 = 86 mg/l) and the deep-compartment transfer coefficients were K12 (0.013 l/h) and K21 (0.048 l/h) between body and deep tissue compartment. Both oral and i.v. data were well described with these values. Limited single time point brain data from rabbits were analyzed with a lumped brain model assuming the generic model for 2,4-D in rat applies to the rabbit. The model simulations were in good agreement with rabbit plasma, brain, and CSF concentrations at 2 h after i.p. injection. PMID- 7871544 TI - 2-Butanol metabolism by rat hepatic and pulmonary cytochromes P450. AB - Three microsomal enzyme inducers, ethanol, phenobarbital (PB), and beta naphthoflavone (beta NF), were compared for their effects on butanol oxidase activity in rat hepatic and pulmonary microsomes. Four concentrations of 2 butanol (1.0, 5.0, 10, and 33 mM) were used to determine if the effects of induction on 2-butanol metabolism were substrate concentration dependent. Ethanol induced at all substrate concentrations in the liver while PB induced at only the high substrate concentrations (5.0, 10, and 33 mM). beta NF did not induce at any substrate concentration. 2-Butanol oxidation in the lung was not induced by any of the treatments. Thus, both ethanol and phenobarbital induce hepatic enzymes capable of 2-butanol oxidation, and the isozyme(s) induced by the latter has a somewhat lesser affinity for this alcohol. PMID- 7871545 TI - Polychlorinated biphenyl-induced suppression of cytotoxic T lymphocyte activity: role of prostaglandin-E2. AB - Prostaglandin-E2 (PGE2) was investigated for its role in suppression of splenic cytotoxic T lymphocyte (CTL) activity following exposure to 3,3',4,4',5,5' hexachlorobiphenyl (HxCB) in mice. Following i.p. alloantigen injection, PGE2 levels significantly increased in peritoneal fluid and in spleen cell culture supernatants. HxCB exposure (1) significantly elevated PGE2 levels above control in peritoneal fluid, (2) significantly reduced production of PGE2 by spleen cells, and (3) did not alter PGE2 production by peritoneal cells. The levels of PGE2 observed were below (> 100-fold) those shown by others to cause immune suppression, and splenic CTL activity was unaltered by indomethacine treatment sufficient to reduce peritoneal PGE2 to undetectable levels. We conclude that altered PGE2 production is not involved in suppression of CTL activity by HxCB. PMID- 7871546 TI - Decreased biliary glutathione content is responsible for the decline in bile salt independent flow induced by ethinyl estradiol in rats. AB - Glutathione appears to be a major osmotic factor in the generation of bile salt independent flow (BSIF). This study was designed to investigate its importance in the pathology of 17-alpha-ethinyl estradiol (EE)-induced cholestasis. Five-day EE treatment at the dose level of 5 mg/kg/day significantly decreased bile flow (57% of controls) and biliary glutathione secretion. Evaluation of the contribution of bile salt dependent flow (BSDF), glutathione dependent flow (GSDF) and the bile flow generated independently of both bile salts and glutathione (BS-GSIF) revealed that EE decreased all portions of the flow (63, 44 and 52% of control values, respectively). At 4 and 20 h after a single administration of the same EE dose, a significant diminution of bile flow was noted (decreases of 17 and 29%, respectively) in association with a significant fall in biliary glutathione content. Under these conditions, BSDF and BS-GSIF were not modified (98 and 112% of control BSDF values, respectively; 96 and 99% of control BS-GSIF values, respectively) while GSDF was decreased markedly, representing 65 and 50% of control values. Biliary glutathione secretion was diminished without modification of liver and blood glutathione concentration or redox status following single EE dose whereas, after 5 days of EE treatment, a significant increase in liver glutathione was observed, suggesting that EE may interfere with the glutathione secretory process. This study demonstrates that EE rapidly alters biliary glutathione content, leading to a marked decline in GSDF. This reduction may explain the decrease in BSIF produced by EE at the outset of cholestasis. PMID- 7871547 TI - Effects of methoxychlor on skin tumor development. AB - Organochlorine pesticides increase the incidence of liver cancer through a multistage process involving tumor promotion. Mirex, an organochlorine pesticide has been shown to be a tumor promoter in mouse skin. In the present study, the effects of methoxychlor, a commonly used organochlorine pesticide, on the development of papillomas in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin and induction of mouse epidermal ornithine decarboxylase (ODC) activity were investigated and compared with 12-O-tetradecanoylphorbol-13-acetate (TPA), a well-known tumor promoter. Methoxychlor neither caused tumor development nor induced epidermal ODC activity. However, TPA resulted in 100% tumor incidence and 8.8 tumors per mouse after 20 weeks of promotion, and induced epidermal ODC activity. PMID- 7871548 TI - Age-related changes in benzene disposition in male C57BL/6N mice described by a physiologically based pharmacokinetic model. AB - A physiologically based pharmacokinetic (PBPK) model was developed to describe the disposition of benzene in 3- and 18-month C57BL/6N mice and to examine the relevant physiologic and/or biochemical parameters governing previously observed age-related changes in the disposition of benzene. The model developed was based on that of Medinsky et al. (Toxicol. Appl. Pharmacol. 99 (1989) 193-206), with the inclusion of an additional rate constant for urinary elimination of benzene metabolites. Experimentally determined tissue partition coefficients for benzene in 3- and 18-month mice, as well as actual body weights and fat compartment volumes, were included as part of the model. Model simulations were conducted for oral exposure of 3-month mice to 10 and 200 mg benzene/kg and for oral exposure of 18-month mice to 10 and 150 mg benzene/kg. Total amount of benzene metabolized, as well as metabolism of benzene to specific metabolites and their elimination, was simulated. Modeling results for total amount of benzene metabolites eliminated in urine over a 24-h period at 10 mg/kg showed that a greater total amount of benzene metabolites would be excreted by 18-month versus 3-month old mice. At saturating doses of 150 and 200 mg/kg, total amount of benzene metabolites excreted 24 h post-dose was predicted to be equivalent in 18 month mice and 3-month old mice, but the rate of elimination over time was shown to be decreased in 18-month vs. 3-month mice. Decreased urinary elimination of total benzene metabolites was simulated by a smaller renal elimination rate constant in 18-month vs. 3-month mice, which is consistent with decreased renal blood flow noted in aging rodents. These model predictions were consistent with observed in vitro and in vivo experimental data. Model simulations for production of specific metabolites from benzene and elimination in urine agreed well with experimental data in showing no significant age-related changes in formation of benzene metabolites, with the exception of hydroquinone conjugates. Model simulations and experimental data showed decreased total urinary elimination of hydroquinone conjugates in 18-month vs. 3-month mice. The change in hydroquinone conjugate elimination with age was simulated in modeling experiments as an age related increase in Km for production of hydroquinone conjugates from benzene. The results of this study indicate that age-related changes in physiology are primarily responsible for altered disposition of benzene in aged mice and suggest that concentrations for toxicity of benzene and/or metabolites may differ in target tissues of aged mice. PMID- 7871549 TI - Role of kidney S9 in the mutagenic properties of 1,2-dibromoethane. AB - The mutagenic properties of 1,2-dibromoethane (DBE) were studied in the Ames Salmonella typhimurium assay using the strains TA 1535 and TA 100. Kidney S9 fraction alone did not modify the direct mutagenic activity of DBE; but an addition of kidney S9 to liver S9 fraction yielded a higher mutagenic activity of DBE than with liver S9 fraction alone. Moreover, the addition of glutathione (GSH) to kidney S9 increased the mutagenic activity of DBE. Methimazole, a competitive inhibitor of the flavin-containing monooxygenase, reduced mutagenic activity suggesting that this enzyme may contribute to renal damage from DBE. No mutagens could be detected in the urine of rats treated with DBE. PMID- 7871550 TI - The pentachlorophenol metabolite tetrachloro-p-hydroquinone induces the formation of 8-hydroxy-2-deoxyguanosine in liver DNA of male B6C3F1 mice. AB - Tetrachloro-p-hydroquinone (TCHQ), the major metabolite of pentachlorophenol (PCP) in mammalian systems, is known to autoxidize to its semiquinone radical under physiological conditions. In this way, PCP could present a potent source of reactive oxygen species (ROS) during metabolization. ROS contribute to numerous modifications of DNA. Formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), a product of hydroxyl radical attack on DNA, is monitored as a marker of a major genetic lesion induced by agents which produce oxygen radicals. We studied the properties of TCHQ for the induction of oxidative DNA damage in vivo. Male B6C3F1 mice were fed a diet containing TCHQ for 2 and 4 weeks. These experiments resulted in an enhancement of about 50% of the 8-OH-dG portion in liver DNA after administration of 300 mg TCHQ/kg body wt./day for 2 weeks. Control levels did not change over the periods of 2 and 4 weeks, respectively. In contrast to these results, a single i.p. injection of 20 or 50 mg/kg body wt. did not affect the 8 OH-dG content after 6 and 24 h, respectively. These data may support a possible contribution of ROS to the carcinogenicity of PCP. PMID- 7871551 TI - Program- and method-related determinants of first DMPA use duration in rural Bangladesh. AB - This article examines the determinants of first-time use durations of the injectable contraceptive Depo Medroxy Progesterone Acetate (DMPA) for rural Bangladeshi women. The method's side effects were defined by 200 first-time users in Matlab district during lengthy, open-ended interviews. Women with many children used the method longer than did women of low parity. Those who experienced side effects had shorter use durations than those who did not, and those who cited heavy bleeding as their main problem discontinued use soonest. Women whose husbands approved of family planning had significantly longer use durations than those whose husbands disapproved. Respondents who adopted DMPA because of perceived positive aspects of the drug used it longer than those who chose it for other reasons. Results of the study underscore the importance of viewing side effects in a specific social and cultural context. Expanded side effects counseling for women and their husbands is needed. PMID- 7871552 TI - Indicators for measuring the quality of family planning services in Nigeria. AB - This article presents the Situation Analysis approach as a means of collecting data that can be used to assess the quality of care provided by family planning service-delivery points (SDPs), and describes the quality of services offered in Nigeria. Elements of the quality of services provided at 181 clinical service delivery points in six states of Nigeria are described. The substantive results from the study suggest that although most of the 181 service points sampled are functional, the quality of care being provided could be improved. Illustrative scores for these indicators and elements of the Bruce-Jain framework are given. By comparison with contraceptive prevalence surveys, the Situation Analysis approach is still in its early stages. Some methodological issues are raised here and future directions for strengthening the validity and applicability of the approach are discussed. PMID- 7871553 TI - User characteristics and oral contraceptive compliance in Egypt. AB - Results from the 1988 Egypt Demographic and Health Survey show that many women are not taking oral contraceptives in a manner that ensures full protection by the method. Reports from 1,258 current pill users show a range of incorrect use; 63 percent of women surveyed reported an interruption in their use of the pill in the past month, and of those women, only 40 percent took the correct action when they missed a pill. The majority (89 percent) did not wait the correct number of days between packs. Multivariate analysis revealed that rural women were more likely to take pills out of sequence, compared with their urban counterparts. Failure to take a pill within the previous month was strongly associated with the experience of side effects. The younger women surveyed were more likely to know the correct interval between pill packs than were older women; and women who wanted more children were more likely to know the correct interval than those who did not. The use patterns exhibited by the pill users may be the result of their receiving confusing, incorrect, or incomplete information, and highlight the need to provide women with accurate, updated, and comprehensible information about oral contraceptives. PMID- 7871554 TI - Estimates of contraceptive prevalence based on service statistics and surveys in Gujarat State, India. AB - This report demonstrates that the estimates of contraceptive prevalence based on surveys are substantially lower than those based on the service statistics generated by the Indian family planning program. The reasons for this discrepancy were examined by contacting a subsample of acceptors recorded by female health workers as users in their registers. This inquiry indicated that the health workers themselves knew that 15-39 percent of the women who had been recorded as users of reversible methods were not really using them. About 19-27 percent of the recorded users of IUDs and only 3-4 percent of the recorded condom users confirmed use of the devices. Overall, the nonusers formed 59 and 64 percent of the recorded users contacted in Bharuch and Panchmahals districts, respectively. The estimates of nonuse of contraceptives in the follow-up survey are high enough to reconcile most of the observed discrepancy between the two sets of estimates of contraceptive prevalence. PMID- 7871555 TI - The Bali Indirect Maternal Mortality Study. AB - The Bali Indirect Maternal Mortality Study (BIMMS) was conducted in Bali Province, Indonesia in 1991. The objective of the study was to evaluate the indirect sisterhood method for estimating maternal mortality, using a prospective (direct) community-based survey undertaken from 1980 to 1982 among women of reproductive age (Reproductive Age Mortality Survey, or RAMOS) as a comparison. The BIMMS maternal mortality ratio was 331 per 100,000 live births adjusted for 1982. This ratio is similar to the RAMOS one prior to its adjustment, of 359 per 100,000 live births. The sisterhood method was faster, cheaper, and appears to be as accurate as direct methods. PMID- 7871556 TI - Kenya 1993: results from the Demographic and Health Survey. PMID- 7871557 TI - Both alloantigen-dependent and -independent factors influence chronic allograft rejection. PMID- 7871558 TI - Retrievable, replaceable, macroencapsulated pancreatic islet xenografts. Long term engraftment without immunosuppression. AB - Prevention of rejection and prolongation of graft survival are critical to achieving successful islet cell transplantation. Various techniques have been utilized to prolong graft survival. Recently, protection of pancreatic islets from host immune mechanisms by isolating the islets in artificial membranes has emerged as an attractive alternative to the use of immunosuppression. In this Rapid Communication, we describe a novel method for macroencapsulation of rat islets in hydrophilic macrobeads made with various combinations of agarose, collagen, and Gelfoam. Encapsulated xenotypic islets were placed intraperitoneally in mice in which diabetes was induced by streptozotocin. The encapsulated xenografts maintained normoglycemia > 170 days. Recipients mice had normal glucose tolerance tests, which indicates that the islets in the macrobeads were functioning as they would in an intact pancreas. Macrobeads retrieved up to 103 days after transplantation showed no evidence of tissue reaction or local inflammation. These retrieved macrobeads could also be retransplanted and replaced. Our studies indicate that the agarose-collagen/Gelfoam macrobeads we have developed serve both to protect islet xenografts from rejection and to provide a microenvironment in which the islets maintain and support their normal function in vivo. Because they may be retrieved after implantation and replaced, these macrobeads may be suitable for human clinical islet cell xenotransplantation. PMID- 7871559 TI - Apparent resistance to immunosuppression of MHC-matched corneal transplants. PMID- 7871560 TI - Extrinsic sympathetic reinnervation after intestinal transplantation in rats. AB - Although extrinsic denervation is inevitable after intestinal transplantation and leads to poor intestinal function, little is known about the occurrence of extrinsic reinnervation. In this study, extrinsic sympathetic reinnervation was investigated morphologically following syngeneic intestinal transplantation performed on male Lewis strain rats. At 1, 3, 6, 9, 15, and 27 weeks after transplantation, the graft mesenteric arteries and their branches in the intestinal wall were histochemically examined by a glyoxylic acid method demonstrating perivascular sympathetic nerve fibers. At 3 weeks after transplantation, extrinsic sympathetic reinnervation was recognized in the graft mesenteric arteries, where it traversed the arterial anastomosis and extended along the course of the mesenteric arteries from proximal to distal. The degree of reinnervation in the mesenteric arteries was similar to the results obtained in the simple denervation model. The transplanted intestinal tract itself was sympathetically denervated for at least 9 weeks after transplantation, and reinnervation was not recognized until 15 weeks after transplantation. Reinnervation extended into the intestinal wall in every preparation, and the enteric nerves began to be reinnervated at 27 weeks after transplantation, but the density was still at a low level and complete extrinsic reinnervation of the graft would seem to require a much longer time to reestablish itself. PMID- 7871561 TI - The value of posttransplant monitoring of interleukin (IL)-2, IL-3, IL-4, IL-6, IL-8, and soluble CD23 in the plasma of renal allograft recipients. AB - Over the past few years, the central role of cytokines in the amplification of the immune response has been reported and several studies have examined the relationship between the plasma level of individual lymphokines during renal allograft rejection. The aim of the present investigation was to study simultaneously IL-2, IL-3, IL-4, IL-6, IL-8, and soluble CD23. Analysis of results has allowed both the prognostic value and any possible interrelationships between the measured cytokines to be determined. We studied 16 renal transplant recipients for the first 14 days after transplantation. Seven patients showed clinical evidence of acute allograft rejection and 5 showed excellent stable graft function with no signs of rejection. Primary nonfunction was seen in 4 patients. The plasma levels of each cytokine were measured by commercially available ELISA and immunoradiometric assay kits. As reported in previous studies, plasma IL-2 levels, whenever found at detectable levels, were predictive of impending graft rejection. Serial monitoring of IL-4 and IL-6 was more reliable for the differential diagnosis of rejection, particularly toward the end of the first week after transplantation. IL-3, IL-8, and soluble CD23 were not diagnostic or predictive of rejection, due to the occurrence of significantly high levels in transplant patients who showed no evidence of clinical rejection. While the value of cytokine monitoring has been shown in this study, it should be remembered that infection, although not seen in these studies, may have a profound affect on the results obtained. PMID- 7871562 TI - Incidence, determinants, and consequences of subclinical noncompliance with immunosuppressive therapy in renal transplant recipients. AB - In this descriptive cross-sectional study, we investigated the incidence, determinants, and consequences of subclinical noncompliance with immunosuppressive therapy in 150 adult renal transplant recipients with more than one year posttransplant status. Symptom frequency and symptom distress, and self care agency were measured by the Transplant Symptom Frequency and Symptom Distress Scale, and the Appraisal for Self-Care Agency Scale, respectively. The Long-Term Medication Behavior Self-Efficacy Scale and a renal transplant knowledge questionnaire were developed as part of this study to measure perceived self-efficacy and knowledge of the therapeutic regimen. Demographic variables were also measured. The incidence of subclinical noncompliance with immunosuppressive therapy as assessed by interview was 22.3%. Compliers and noncompliers differed significantly on the variables of marital status (P = 0.03), situational-operational knowledge (P = 0.02), self-care agency (P = 0.03), and perceived self-efficacy related to long-term medication intake (P = 0.048). A logistic regression model using gender, marital status, perceived self-efficacy, self-care agency, knowledge about medication administration and signs of infection, and situational operational knowledge as predictor variables, revealed a 78.6% correct classification of compliers versus noncompliers and a sensitivity ratio of 95.9%. There were significantly more acute late rejection episodes (P = 0.003) in the noncompliant group. Graft survival at 5 years in this group was also significantly lower (P = 0.03) than the compliant patients. No significant difference was found in terms of the occurrence of chronic rejection episodes or in terms of patient survival at 5 years. Because noncompliance is a risk factor for negative clinical outcome in renal transplant recipients, it is of utmost importance to develop intervention strategies to enhance compliance in this population by using determinants identified in exploratory studies. PMID- 7871563 TI - Effect of OKT3 in steroid-resistant renal transplant rejection. AB - Between January 1, 1982, and November 1, 1986, 169 cadaver renal graft transplantations were performed at this hospital with CsA as induction therapy. OKT3 was not available in this period. Of these grafts, 15.9% were lost within 6 months, 10.7% from acute rejection (AR). Between November 1, 1986, and October 1, 1992, 483 cadaver renal graft transplantation were performed. Induction therapy included CsA and OKT3 was available. Of these grafts, 8.7% were lost inside 6 months, 3.1% from AR. Of these last 483 grafts, 113 received 125 courses of OKT3. Ten courses were prophylactic, and 115 courses in 103 patients were for rejection resistant to steroid therapy (biopsy proven in all but 2 cases. Ninety-three percent of rejection episodes treated with OKT3 responded, at least initially. Graft survival in OKT3-treated patients was 81%, 77%, and 76% at 6 months, 1 year, and 2 years, respectively. In contrast, graft survival in steroid-resistant rejection during the first period (without OKT3) was 59%, 57%, and 57% at these intervals. There were 8 infective deaths within 6 months in the 113 OKT3-treated patients, compared with 2 in the 343 who did not receive OKT3 (P < 0.001). There were 7 viral deaths in the OKT3 group compared with none in those not receiving OKT3 (P < 0.001). Prophylaxis with oral acyclovir and cotrimoxazole was instituted in October 1990 in OKT3-treated patients and ganciclovir use was increased. Since this change, no further viral deaths have occurred. OKT3 is a very effective antirejection agent, but its use is associated with an increased mortality from viral infections. With appropriate prophylaxis and treatment, however, this mortality can be reduced. PMID- 7871564 TI - Delayed omega-3 fatty acid supplements in renal transplantation. A double-blind, placebo-controlled study. AB - An earlier reported trial suggests that omega-3 fatty acids in fish oil supplements at 6 g/day with administration commencing at the time of engraftment may reduce acute CsA renal dysfunction. When started at the time of renal transplant, there are improvements in renal hemodynamics and blood pressure, and a decrease in rejection episodes. To examine the effect of later introduction of omega-3 fatty acids, 133 cadaver renal transplant recipients received CsA, prednisone, and AZA for 16 weeks (period 1). If patients were stable without rejection or infection activity, they were randomized to 9 g of eicosapentanoic acid (EPA), 18 g of EPA, 9 g of corn oil, or 18 g of corn oil in 1-g capsules as supplements. Glomerular filtration rate, renal blood flow, number of rejection episodes, blood pressure, and episodes of CsA nephrotoxicity were followed for 26 weeks in a double-blind manner (period 2). Ninety patients were evaluable and completed the protocol. There were 50 corn oil placebo patients, 22 low dose EPA patients, and 18 high dose EPA patients. In period 1, there were 27 rejection episodes in 21 patients without differences among subsequent treatment groups. In period 2, there were 13 rejection episodes in 4 patients. No patient with an EPA level in plasma statistically higher than placebo had a rejection episode. All allografts functioned for the entire 6 months with none lost to rejection. All 5 episodes of acute CsA nephrotoxicity occurred in placebo-treated patients without differences in whole blood CsA among toxic patients, other placebo patients, and EPA-treated recipients. At the end of the study, there were no differences in glomerular filtration rate, renal blood flow, or creatinine clearance among groups. Diastolic blood pressure fell by 9 mmHg during period 2 in high dose fish oil recipients and by 10 mmHg in low dose fish oil recipients (P < 0.05), while it rose by 2 mmHg in placebo patients. No serious adverse effects of EPA supplements were noted, although compliance based on plasma EPA was erratic. Based on our experience and that in the literature, administration of omega-3 fatty acids for purposes of kidney protection would seem to be most useful when started early after surgery. Late administration in our study was associated with minor clinical benefits. PMID- 7871565 TI - Evidence demonstrating poor kidney graft survival when acute rejections are associated with IgG donor-specific lymphocytotoxin. AB - The current prospective investigation was conducted to determine whether development of IgG donor-specific lymphocytotoxins detected at the onset of acute rejections was predictive of a poor-prognosis acute rejection. Between January 1990 and August 1993, 206 kidney transplants were performed. Cadaver kidney recipients were managed with antilymphocyte globulin as induction therapy and all recipients (i.e., cadaver and living related donor kidneys) received triple immunosuppressive therapy, i.e., CsA, AZA, and prednisone. Rejections were treated with intravenous Solu-Medrol and OKT3. Presence of donor-specific IgG lymphocytotoxin was detected by using dithiothreitol-pretreated sera (obtained at onset of rejection) and frozen donor cells. In addition, percentage of panel reactive antibody was determined on this dithiothreitol-pretreated sera. Of the 82 patients with biopsy-proven acute rejections, 19 were found to have developed donor-specific IgG lymphocytotoxin and a marked increase in panel reactive antibody. One-year graft survival in this group was dismal (16%), despite OKT3 therapy. Over 90% of these patients lost their graft within 2 months of rejection diagnosis. In 63 recipients who had acute rejections without development of IgG anti-HLA antibody, 1-year graft survival was 72%. The majority of these patients lost their grafts from chronic rejection. No anti-HLA activity was found in patients who did not have rejection episodes. Based on this study, evidence indicates that assaying for IgG donor-specific antibody at time of rejection is a valuable tool for selecting a subset of patients with poor-prognosis acute rejections. Identifying this subset will become important as we enter an era of new immunosuppressive agents. PMID- 7871566 TI - Impact of pretransplant renal function on survival after liver transplantation. AB - To determine the effect of pretransplant liver function on survival following orthotopic liver transplantation and to quantify the effects of cyclosporine administration on long-term renal function in patients undergoing liver transplant, we performed an analysis of a prospectively maintained database. Data from 569 consecutive patients undergoing liver transplantation alone who were treated with CsA for immunosuppression were used for this study. Actuarial graft and patient survival rates were calculated using Kaplan-Meier statistics. Glomerular filtration rates, serum creatinine, and the use of various immunosuppressives were analyzed for this study. The initial analysis demonstrated that patients presenting for liver transplant with hepatorenal syndrome have a significantly decreased acturial patient survival after liver transplant at 5 years compared with patients without hepatorenal syndrome (60% vs. 68%, P < 0.03). Patients with hepatorenal syndrome recovered their renal function after liver transplant. Patients who had hepatorenal syndrome were sicker and required longer stays in the intensive care unit, longer hospitalizations, and more dialysis treatments after transplantation compared with patients who did not have hepatorenal syndrome. The incidence of end-stage renal disease after liver transplantation in patients who had hepatorenal syndrome was 7%, compared with 2% in patients who did not have hepatorenal syndrome. To more fully examine the effect of pretransplant renal function on posttransplant survival, the non-hepatorenal syndrome patients were divided into quartiles depending upon their pretransplant renal function. The patients with the lowest pretransplant renal function had the same survival as the patients with the highest pretransplant renal function. In addition, there was no increased incidence of acute or chronic rejection in any of the groups. The patients with the lower pretransplant renal function were treated with more azathioprine to maintain renal function and had a negligible decrease in glomerular filtration rate following transplant. Conversely, patients with the highest level of renal function pretransplant had a 40% decline in renal function in the first year, but maintained stable renal function up to 4 years after transplant. We conclude that pretransplant renal function other than hepato-renal syndrome has no effect on patient survival after orthotopic liver transplant. Renal function after liver transplant is stable after an initial decline, despite continued administration of CsA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7871567 TI - Clinical impact of replacing Minnesota antilymphocyte globulin with ATGAM. AB - In August 1992, we replaced Minnesota antilymphocyte globulin (MALG) with lymphocyte immune globulin, antithymocyte globulin (equine) (ATGAM) in our immunosuppression protocols. The clinical impression of increased graft rejection prompted our assessment of the effect of this change on patient and graft outcome. The initial study group consisted of 426 renal transplant recipients transplanted between October 1, 1987, and September 21, 1993. After exclusions, 388 transplant events, with a minimum 8-month follow-up, made up the final study cohort: 323 patients received MALG and 65 received ATGAM. Immunosuppression included intravenous methylprednisolone, oral prednisone, oral AZA, CsA in some cases, and intravenous MALG or ATGAM, 15 mg/kg/day, for 7 to 14 days. Acute rejection was treated with high dose intravenous steroids and steroid-resistant episodes were treated additionally with either MALG or OKT3. Statistical comparisons were stratified for multiple patient characteristics and treatment variations. There was a greater incidence of rejection in general, and a higher incidence of steroid-resistant episodes requiring subsequent antilymphocyte globulin therapy (P = 0.0073) in patients receiving ATGAM versus MALG. No difference was seen in the incidence of CMV infection or blood-borne sepsis. Lymphoma occurred in 3 MALG and 2 ATGAM recipients. MALG recipients were significantly less likely to experience rejection within the first 60 days after transplant (P = 0.0127 using unstratified data; P < 0.0001 when data were stratified for patient characteristics). The relative risk of acute rejection for posttransplant days 5, 7, 10, and 14 was consistently higher for ATGAM-treated patients. We conclude that MALG and ATGAM are not equivalent drugs, and that MALG is a more effective immunosuppressant, and is just as safe as ATGAM in our protocol environment. PMID- 7871568 TI - Induction of anterior chamber-associated immune deviation with lymphoreticular allogeneic cells. AB - Immune privilege in the anterior chamber of the eye results in part from a selective deficit in delayed hypersensitivity that is elicited by antigenic materials placed in this unique tissue site. This stereo-typical systemic immune response (anterior chamber-associated immune deviation [ACAID]) to intraocular antigen can also be evoked in naive mice by the intravenous injection of syngeneic peritoneal exudate cells (PEC) that have been incubated overnight with a soluble antigen in the presence of supernatants of cultured iris and ciliary body (I/CB) cells or with transforming growth factor (TGF)-beta. To determine whether a similar protocol could be used to induce ACAID to transplantation antigens expressed on allogeneic PEC, we conducted experiments with allodisparate PEC donors and recipients selected to differ at loci dictating MHC and/or minor histocompatibility antigen. Recipients of I/CB supernatant-treated PEC from donors disparate for class I and/or class II antigens, as well as donors disparate only for minor H antigens, were specifically unable to display donor specific delayed hypersensitivity, whereas recipients of PBS-treated allogeneic PEC developed intense donor-specific delayed hypersensitivity. We conclude that allogeneic PEC that have been cultured with I/CB supernatant overnight create an alloantigen-specific ACAID-inducing signal that confers ACAID on naive recipient mice. PMID- 7871569 TI - Differential effects of the immunosuppressive agents cyclosporine and leflunomide in vivo. Leflunomide blocks clonal T cell expansion yet allows production of lymphokines and manifestation of T cell-mediated shock. AB - The effects of leflunomide and CsA on immune responses in vitro and in vivo were investigated. Like CsA, leflunomide inhibited mitogen- or antigen-driven T cell proliferation in vitro. However, leflunomide impaired neither the capability of T cells to produce IL-2 and IL-4, nor the expression of IL-2R, that is, the acquisition of competence. In contrast to CsA, the IL-2-driven growth of secondary T cells was blocked by leflunomide. Cell cycle analyses revealed that activated T cells did not enter S phase of the cell cycle in the presence of leflunomide. Next, the effects of leflunomide and CsA on the T cell response toward the bacterial superantigen (SAg) staphylococcal enterotoxin B (SEB) were analyzed in vivo. SEB-induced early deletion (apoptosis) of a fraction of SEB reactive V beta 8+ T cells and IL-2R expression were not impaired by either CsA nor leflunomide. On the other hand, both CsA and leflunomide prevented V beta 8 selective clonal T cell expansion and generation of SEB-specific cytolytic activity. In contrast to CsA, leflunomide treatment permitted in vivo SEB-induced production of T cell-derived lymphokines (IL-2 and TNF). Further, leflunomide failed to protect D-galactosamine-sensitized mice from SEB-induced, T cell mediated lethal shock, whereas CsA was fully protective. Manifestation of SEB induced T cell anergy was not impaired by leflunomide. Our results provide evidence that CsA and leflunomide differ significantly in their functional properties to suppress immune responses in that both agents inhibit T cell functions linked to clonal expansion, while leflunomide does not inhibit lymphokine secretion and thus permits lymphokine-mediated immune functions. PMID- 7871570 TI - Tolerance induction in a fully allogeneic combination using anti-T cell receptor alpha beta monoclonal antibody, low dose irradiation, and donor bone marrow transfusion. AB - In a murine strain combination disparate in both H-2 antigens and minor histocompatibility antigens consisting of C57BL/6 (B6; H-2b, Mls-1b) mice as recipients and AKR/J (AKR; H-2k, Mls-1a) mice as donors, we reported that the administration of anti-TCR-alpha beta mAb nonspecifically suppresses the ability to reject allografts. However, such an effect was only temporary and all grafts were eventually rejected within 40 days in the anti-TCR-alpha beta mAb-treated mice. In this study, to induce donor-specific tolerance, the transfer of donor bone marrow cells was added to the administration of anti-TCR-alpha beta mAb but donor bone marrow cells were rejected and failed to cause donor-specific unresponsiveness. After donor bone marrow cell transfer in the anti-TCR-alpha beta mAb-treated mice, the B cells of the recipients were observed along with the production of antidonor antibody. To abolish the residual lymphocyte populations, low dose irradiation was also added. A long-lasting skin allograft tolerance can be achieved by the tolerance system, in which low dose irradiation was added to the combined treatment with anti-TCR-alpha beta mAb and transfer of donor bone marrow cells. Such a protocol also established central and peripheral chimerism, which suggests that hematopoietic chimerism is necessary to maintain the tolerance. B cells were completely abolished in recipients given this combined treatment and their antibody production against donor antigens after the transfer of donor bone marrow cells was also completely suppressed. A possible role of B cells in the rejection of donor bone marrow cells before the establishment of chimerism is discussed. PMID- 7871571 TI - Peptides derived from alpha-helices of allogeneic class I major histocompatibility complex antigens are potent inducers of CD4+ and CD8+ T cell and B cell responses after cardiac allograft rejection. AB - We studied the rejection of cardiac allografts in a rat strain combination (PVG.R8 to PVG.1U) disparate for a single class I MHC antigen (RT1.Aa) to test the extent by which this molecule is recognized as peptides in association with recipient MHC molecules during graft rejection and the contribution of this recognition process to the rejection reaction. Three synthetic peptides that correspond to the portions of alpha-helices of the alpha 1 (P1, P2) and alpha 2 (P3) domains of the donor RT1.Aa molecule were used in this study. Splenocytes from heart allograft recipients at rejection responded in a proliferation assay to all 3 peptides and in a cytotoxic assay to peptides P1 and P2. The peptide mediated proliferation and cytolytic reactions were blocked by antibodies against CD4/class II MHC and CD8 molecules. Serum from graft recipients at rejection contained significant titers of antibodies to peptides. Presensitization of graft recipients with the peptides resulted in a marked increase in peptide-mediated T cell and antibody responses. Although all 3 peptides were effective in eliciting active immune responses, the P3-mediated response was minimal when compared with those mediated by P1 and P2. Recipients presensitized with the peptides rejected their grafts in 5 days compared with 6 days for unsensitized animals. Recipients presensitized with donor-irradiated splenocytes and aortic endothelial cells, on the other hand, rejected their grafts in 1 and 3 days, respectively, which suggests that immunization with the whole RT1.Aa molecule is required to stimulate accelerated rejection of the graft. This rejection was associated with high titers of donor cell-specific antibodies that exhibited moderate cross reactivity with the peptides. Our results clearly demonstrate that (1) the donor RT1.Aa molecule is recognized as peptides in the context of recipient class I and class II MHC molecules during the rejection of heart allografts, and (2) peptides derived from this molecule are highly immunogenic in that they contain epitopes recognized by CD4+ and CD8+ T cells and alloantibodies. Immune responses elicited by these peptides, however, did not significantly affect the rate of rejection. These results suggest that acute rejection of allografts may be mediated primarily by the direct recognition of intact MHC molecules. PMID- 7871572 TI - Absence of hyperacute rejection in pig-to-primate orthotopic pulmonary xenografts. AB - The shortage of organ donors for transplantation is more pronounced for the lung than for any other solid organ. To address this problem, we evaluated the feasibility of pulmonary xenotransplantation. Preliminary investigations demonstrated that orthotopically placed pig lungs in cynomologous monkey recipients could be engrafted up to 9 hr after reperfusion without evidence of hyperacute rejection. In this study, the rejection reaction of pig lungs transplanted orthotopically into baboons (n = 6) was further investigated by ELISA and immunohistochemistry. Four baboon recipients were killed at 24 hr and 2 recipients were killed at 72 hr after transplantation. Pulmonary arterial flow measurements demonstrated flow to the grafts, and systemic arterial and xenograft pulmonary venous blood gas analysis suggested function of the donor lungs during the course of engraftment. Serum levels of baboon anti-pig endothelial cell xenoantibody were normal and decreased minimally over time. Immunohistochemical staining of biopsies demonstrated trace IgG and IgM along graft endothelium 2 hr after reperfusion. At 8 hr, biopsy samples showed no immunoglobulin bound to endothelial cells. Staining for complement was negative. Fibrin and platelets were detected along xenograft endothelium. Despite these findings, the lung xenografts appeared injured and clinically rejected. During the first 8 hr after reperfusion, the grafts were hyperemic and subsequently became focally ecchymotic. Chest x-rays showed progressive pulmonary congestion. These findings suggest that the lung may be relatively resistant to antibody-mediated hyperacute rejection and efforts are being directed toward identifying the mechanism of the observed xenograft lung injury. PMID- 7871573 TI - Nitric oxide and arachidonate metabolism in ischemia-reperfusion associated with pancreas transplantation. AB - The role of eicosanoid metabolism and its relationship with nitric oxide production in the ischemia-reperfusion associated with pancreas transplantation in the rat is explored in this study. Twenty-six male Sprague-Dawley rats were randomized into 3 groups, as follows: group 1, control animals not surgically manipulated; group 2, pancreas transplantation, after 12 hr of organ preservation in University of Wisconsin solution; group 3, same as group 2 but with administration of NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) (10 mg/kg) before organ revascularization. The results show posttransplantation increases in edema and in 6-keto-prostaglandin F1 alpha (x1.9), thromboxane B2 (x4), and prostaglandin E2 (x5) levels in pancreatic tissue. Nitric oxide synthase inhibition reversed the increases in edema and eicosanoid production, which suggests that eicosanoid generation in the recipient rat would be mediated, in part, through a nitric oxide-dependent mechanism. PMID- 7871574 TI - Successful myoblast allotransplantation in mdx mice using rapamycin. PMID- 7871575 TI - Effect of rapamycin on morphological and functional parameters in the kidney of the rabbit. PMID- 7871576 TI - Effects of delayed intrathymic donor splenocyte infusion on cardiac allograft survival in antilymphocyte serum-treated rats. PMID- 7871577 TI - Recirculation of cytolytic T cells from a single lymph node during an immune response to allogeneic leukocytes. PMID- 7871578 TI - Triplets born to a kidney transplant recipient. PMID- 7871579 TI - Treatment of anastomotic ostial allograft and renal artery stenosis with the Palmaz stent. PMID- 7871581 TI - Transplantation of the liver from a donor with complete situs inversus and dextrocardia. PMID- 7871580 TI - The role of anti-class II HLA antibodies in heart transplantation. PMID- 7871582 TI - Cyclosporine trough levels, acute rejection, and renal dysfunction after heart transplantation. PMID- 7871583 TI - Reversible nitrofurantoin-induced chronic active hepatitis and hepatic cirrhosis in a patient awaiting liver transplantation. PMID- 7871584 TI - Role of graft in transplantation tolerance. PMID- 7871585 TI - Effect of fenofibrates in heart transplant patients. PMID- 7871586 TI - Pharmaceutical expenses after kidney and kidney-pancreas transplantation. PMID- 7871587 TI - Impressions of imprints. PMID- 7871588 TI - Sense, nonsense and antisense. PMID- 7871589 TI - Why so few pseudogenes in tetraploid species? PMID- 7871590 TI - Homologous ligation: a novel cloning method. PMID- 7871591 TI - The agouti gene: turned on to yellow. AB - The agouti locus was first identified as a result of its effects on the type and temporal deposition of coat color pigments in mammals. Many mutations at the murine agouti locus have now been found, some of which not only affect coat color, but also interfere with diverse biological processes leading to diabetes, obesity, tumor susceptibility and embryonic lethality. Correlations between the genotype and phenotype of agouti mutants, as well as reasons for the pleiotropy of effects caused by agouti mutations, have begun to unfold with the molecular cloning of the agouti gene and its surrounding genomic region. PMID- 7871592 TI - Genes and deafness. AB - Many different genes appear to be involved in the development and function of the mammalian inner ear. Some of the genes involved during early inner ear morphogenesis have been identified using mutations or targetted transgenic interruption, while a handful of genes involved in pigmentation anomalies associated with hearing impairment have been cloned. Several genes involved in syndromic late-onset hearing loss have also been identified. However, the majority of cases of hereditary hearing impairment from childhood probably involve genes expressed in the sensory neuroepithelia of the inner ear, and none of the genes or mutations causing this type of deafness have yet been identified. Here, we review the progress that has been made in finding genes for deafness and in using mouse mutants to elucidate the biological basis of the hearing deficit. PMID- 7871593 TI - GAPs for rho-related GTPases. AB - Ras-related GTP-binding proteins (GTPases) of the rho subfamily play important roles in regulating the organization of the actin cytoskeleton. A large number of multifunctional proteins that can stimulate their intrinsic GTPase activity have been identified. Here, we discuss the nature of such GTPase-activating proteins (GAPs) and their potential importance for cell signalling. PMID- 7871594 TI - Vegetative incompatibility in filamentous fungi: het genes begin to talk. AB - Somatic or vegetative incompatibility is widespread in filamentous fungi. It prevents the coexistence of genetically different nuclei within a common cytoplasm. Cloning the het genes that control this process has been achieved in several species. This has provided essential information on the function of the genes in the biology of fungi and has also led to the formulation of models that may explain similar phenomena in other organisms. PMID- 7871595 TI - [Bone densitometry: principles and indications]. PMID- 7871596 TI - [Lung infections in immunodepressed patients]. PMID- 7871597 TI - [Caustic esophagitis in children: report of 34 cases]. PMID- 7871598 TI - [Tetralogy of Fallot in adults: report of 18 cases]. PMID- 7871599 TI - [Intestinal parasitic diseases among food handlers]. PMID- 7871600 TI - [Refractive disorders in the diabetic patient]. PMID- 7871601 TI - [Value of the corneal examination in the diagnosis of metabolic diseases: report of 21 cases]. PMID- 7871602 TI - [Benign intracranial hypertension. Report of 8 cases]. PMID- 7871603 TI - [Pulmonary pneumocystis in Tunisia. Report of 6 cases]. PMID- 7871604 TI - [Generalized cytosteatonecrosis in the newborn. Report of 3 cases]. PMID- 7871605 TI - [Primary malignant melanoma of the nasal cavity: report of a case]. PMID- 7871607 TI - [Comment on the contribution by B. Hausmann, K. Hudabiunigg: On the risk of fat embolism syndrome after intramedullary nailing in femoral fracture and thoracic injury]. PMID- 7871606 TI - [Replacement of the anterior cruciate ligament by a PET prosthesis (Trevira extra strength) as a salvage procedure in chronically unstable previously operated knee joints. Intermediate to long-term results of a clinical study]. AB - Thirty-one salvage cases of chronically unstable previously operated knees were stabilized by an anterior cruciate ligament prosthesis of polyethyleneterephthalate (Trevira hochfest) and additional repair of concomitant lesions. The patients were followed up at yearly intervals. For the final follow up after 4.4 years 27 patients could be evaluated clinically, radiologically and by several scores. The pre-operative Lysholm score was 59.8 (+/- 16.7). It was raised significantly by the operation to 75.4 (+/- 18.9) after 1 year, but then gradually decreased to 71.4 (+/- 19.6) at the final examination. Similar values were reached for the other scores (OAK, IKDC, VAS). The degree of activity (as estimated by the Tegner activity scale) increased from 2.0 (+/- 2.1) to 3.1 (+/- 1.9). Pre-operative anterior translation revealed a side-to-side difference of 7.5 (+/- 3.4) mm. The stability, which was restored by the operation, gave way a little in the first 2 years up to a side-to-side difference of 2.1 (+/- 2.5) mm, but then remained constant and was measured 2.3 (+/- 2.9) mm after 4.4 years. On the whole, the patients gained a significant improvement from the operation in all investigated parameters. Major complications included 5 ruptures of the synthetic ligament (1 by material fatigue), 1 avulsion of a staple, 1 supracondylar fracture due to 3 closely located staples, 4 cases of arthrofibrosis and 1 case of chronic knee irritation. The gradual deterioration of the operated knees within the follow-up period is mainly caused by the pre existing chronic degenerative changes, which progress in spite of a sufficient stabilization of the central pivot. PMID- 7871608 TI - [Biomechanical principles of after-care in replacement of the anterior cruciate ligament]. AB - The patellar tendon graft replacing the anterior cruciate ligament undergoes histomorphological and biomechanical changes. From literature we can estimate a force of 200 N to be a critical limit of graft load after ACL-plasty in humans. The comparison with the graft loads under various conditions provided the following conclusions: Unlimited passive motion of the knee joint can be done without risk. Early weight bearing is possible. Active extension exercise against gravity could damage the graft in the range of 0 to 20 degrees of flexion in some patients. A rehabilitation protocol has to regard these biomechanical principles. In a prospective study 74 patients underwent rehabilitation according to the protocol described. An extension contracture of more than 10 degrees was seen in 9 patients. In all cases it was due to a notch-impingement or a cyclops. One year after operation 57 patients had a follow up. The side to side-difference in anterior drawer measured with a KT-1000-arthrometer was less than 2 mm in 45 patients. Six patients had difference between 2 and 4 mm. In six patients the difference was more than 4 mm. PMID- 7871609 TI - [Ultrasound follow-up of experimental partial Achilles tendon rupture]. AB - We performed surgically an experimental partial Achilles tendon dissection on 28 New Zealand white rabbits. The changes in the healing process were sonographically followed and documentated in short periods of time for 2 months. The sonographically detectable changes during the healing process underlie certain rules. The changes in sonography can be explained by the histopathology with respect to the theoretics of ultrasound physics. Hematomas and the fibrous scars can be followed closely with sonography. Sonography is a method of high value in the diagnosis of partial and complete tendon tears and with respect to certain limits in the follow-up of the healing process, too. Certain limits in the evaluation of tendon injuries and their follow-up by sonography remain. PMID- 7871610 TI - [Implementing ambulatory prevention of thrombosis with low molecular weight heparin in plaster immobilization of the lower extremity]. AB - Plaster cast immobilisation following trauma is a major risk factor for the development of deep vein thrombosis. In our controlled, randomized and prospective study in patients with minor injuries the incidence of deep vein thrombosis was 4.3% in conservatively treated outpatients with plaster cast immobilisation of the leg (n = 163 control group without prophylaxis). By application of low molecular weight heparin once daily the number of deep vein thrombosis in the prophylaxis group (n = 176) was reduced to 0% (p = 0.006). No severe side effects of low molecular weight heparin were observed. Subcutaneous injections were self-applicated by 89% of males and 72% of females. We conclude that thromboprophylaxis with low molecular weight heparin once daily is effective to reduce the risk of deep vein thrombosis in outpatients with plaster cast immobilisation of the leg. PMID- 7871611 TI - [An unusual early complication in cementless replacement of the hip joint. Case report]. AB - This is the first description of a dislocation of the polyethyleninlay from the cup of a cementless hip prosthesis. Due to a fall of the patient 8 months after the implantation an unspecific complaint arised. In spite of detailed diagnostic no reason could have been found. During the renewed operation we saw the dislocated inlay by mechanical anchorage of the cup and the shaft. Retrospective there were made suggestions how the described complication could be recognized earlier. PMID- 7871612 TI - [Progress and risks in data protection and therapeutic freedom by erroneous interpretation of quality assurance]. PMID- 7871614 TI - [Bacterial toxic shock as a complication of calculous pyelonephritis]. AB - The causes of bacteriotoxic shock were examined in 33 patients (11 lethal outcomes). It has arisen as a complication of treatment given to 7830 patients for urolithiasis. Aggravation of chronic pyelonephritis, occlusion of the urinary tracts, urogenital mucosal and parenchymal injuries, low resistance to infection contribute to microbacteria and their toxins entering blood with resultant bacteriotoxic shock. Transcutaneous operative interventions, therapeutic and diagnostic procedures also produce high risk of blood infection with gram negative microflora, especially in violation of asepsis and antisepsis rules. As shown by microflora tests, the dominating bacteria consisted of opportunistic agents which had acquired the resistance to antibacterial drugs. In view of rapid progression of bacteriotoxic shock therapeutic efforts should be concentrated on fast normalization of hemodynamics, recovery of urine passage, introduction of sorption detoxication, prevention of DIC syndrome. The schemes of combined antibiotic treatment adjusted to the kind of infectious agent are suggested. PMID- 7871613 TI - [The role of ultrasonic scanning in optimizing the therapy of gestational pyelonephritis]. AB - Urinary tracts were examined by ultrasonic scanning (US) of the kidneys in 130 patients with gestational pyelonephritis. The scanning provided a rapid diagnosis of parenchymal and paranephric fat lesions, of urinary tract occlusion, location of concrements, congenital and acquired renal defects, abscesses, carbuncles. The follow-up US controls the inflammation, permitting differential treatment under reduced exposure to x-rays and radionuclides. PMID- 7871616 TI - [Surgical treatment in different variants of the duplicated kidney in children]. AB - The paper details various surgical treatment of double kidney variants. A total of 49 children have been treated, of whom in 3 cases the subdivision was incomplete. The causes and characteristics of the kidney lesions varied. They had arisen most frequently due to tissue embryonal inferiority. The method of operative correction requires a careful approach to parenchymal affection form and degree, to the examination policy and is predetermined by timely and thorough diagnosis. PMID- 7871615 TI - [The microbiocenosis of the intestinal mucosa during the treatment of infectious urogenital diseases with fluorinated quinolones]. AB - Intestinal microecology was studied in 52 patients (47 females and 5 males aged 18-61) with urogenital infections. Group 1 consisted of 35 patients with new onset urogenital infections, group 2 of 17 patients had long-term recurrent urogenital infection. All the patients exhibited abnormal intestinal mucosal flora manifest more definitely in group 2. The microfloral changes comprised reduced count of bifidal bacteria, E. Coli, lactobacteria, occurrence of atypical bacteria. Administration of fluorinated quinolones (abactal or maxaquine) affected aerobic intestinal microflora and insignificantly influenced anaerobic bacteria. It is thought valid to investigate intestinal flora in patients with urogenital infections for taking adequate corrective measures. PMID- 7871617 TI - [Modulit SL-20. Its development and clinical trial]. AB - Modulit SZ-20 represents the third lithotriptor generation comprising the advantages of high disintegration efficacy, operation without anesthesia, combined system of ultrasonic and fluoroscopic localization of the concrements, provision with multifunctional platform. The impulse is generated by a cylindrical electromagnetic spiral with a paraboloid reflector. The waves go through a water cushion and impedance-adapted layer in which the patient is placed. Localization of the concrements is conducted by a special ultrasonic detector operating on-line, or fluoroscopically by an integrated arm C of the x ray unit. In vitro and animal experiments have given evidence for high efficacy of the above lithotriptor, make it possible to evaluate dose-related and reversible renal trauma, to compare similar traumas induced by other lithotriptors. Since 1988 Modulit-SZ-20 has been tested for localization of nephroliths and ureteroliths. Then the attention of the designers was focused on concrement disintegration. After improving the X-ray guidance, the voltage of the generator, analysis of the experience gained, the percentage of disintegration has risen to 94. The authors achieved completed disappearance of the stones in 88% of their patients. SZ-20 Modulit proved effective against choleliths and stones in the biliary ducts as well. This device is recommended as high effective stone-crushing modality of the third generation. PMID- 7871618 TI - [The stimulation of the urodynamics of the upper urinary tract in the combined treatment of urolithiasis]. AB - Sound, vacuum and electrical stimulation of urodynamics on the units Intrafon, Intraton, electric aspirator has been assessed in 311 urolithiasis patients. Sound stimulation of the upper urinary tracts in the presence of ureteroliths improves urodynamics in 88% of cases, in multiple fragments of the stones crashed at impulse lithotripsy in 81.3%. Vacuum exposure of the upper urinary tracts relieves pain in one third of the patients. The highest effect on urodynamics (93.5%) and the concrement dislodgement rate (82.2%) occurred in sound combined with vacuum stimulation. Modification of the direct electrical stimulation of upper urinary tract urodynamics is proposed to recover the tract tonicity. It can be also used in surgical patients with drained tracts for elimination of the stones and fragments as well as for prevention of lithogenesis. PMID- 7871619 TI - [The correction of hyperuricemia in patients with different forms of nephrolithiasis using allopurinol and Allomaron]. AB - Metabolic status was assessed in 48 patients with nephrolithiasis followed-up for 4 years. Allopurinol and allomaron-treated patients were examined biochemically by 17 parameters of the blood and urine. The effects of the drugs were compared. It is concluded that in hyperuricemia up to 0.37 +/- 0.02 mmol/l allomaron is more effective (1--2 pills a day). In higher hyperuricemia allopurinol is preferable (4 pills a day). Allomaron can be also used (1--2 pills a day) under the control of urinalysis. PMID- 7871620 TI - [A preliminary report on the therapeutic effect of laser thermal puncture with the Bozon--PIRT apparatus in urological and gynecological diseases]. AB - The operative parameters of a new unit for laser thermopuncture manufactured in Russia (Novosibirsk, Ecran) are compared to other equipment characteristics. Preheating of the zone to be exposed to laser increases sensibility to infra-red laser radiation. Laser thermopuncture techniques in cystalgia, algodysmenorrhea, enuresis are provided. PMID- 7871621 TI - [Ultrasonic diagnosis in selecting the treatment method for varicocele]. AB - The paper deals with ultrasound diagnosis as a modality able to recognize indications either to surgical or endovascular treatment of varicocele. Forty-two patients aged 12-28 with varicocele degree I-III were examined using sector ultrasonic transducers (3.5,5 MHz) which visualized renal and internal testicular veins. Relevant ultrasonic and phlebographic findings were compared. The impossibility to predict outcomes of the endovascular treatment is attributed to the absence of primary information on the structure of the renotesticular portion of varicocele patients' venous bed. Ultrasonography can provide such information. The detection rate of multiple internal testicular veins and other renotesticular anomalies appears rather high. PMID- 7871622 TI - [Urea and ammonia in the saliva of patients with kidney diseases]. AB - Blood and salivary urea, salivary ammonia were measured in 39 patients: 11 with chronic renal failure stage I-II (group 1), 12 with chronic renal failure stage III (group 2), control subjects without renal diseases (control group of 16 patients). The findings indicated higher levels of salivary urea in group 1 and 2. Salivary and blood urea concentrations correlated, the proportions being 68%, 40.8% and 61% for group 1, 2 and controls, respectively. The treatment of group 1 and 2 patients resulted in parallel changes in blood and salivary urea. In group 2 salivary ammonia reached the amount 5.7 mmol/l against control values 3.0 +/- 0.5 mmol/l. Salivary urea levels reflect the progression of renal dysfunction and may serve a diagnostic criterium. PMID- 7871623 TI - [Prognostic factors in bladder cancer]. AB - DNA distribution was studied in tumor cells of 54 patients with bladder cancer. Diploid and aneuploid distributions were recorded in 34 and 20 cases, respectively. Aneuploid DNA proved to be a negative prognostic factor as 5-year survival of such patients made up 48.2%, the lethality rate being 1.78 (p = 0.04). For diploid tumors the above parameters were 80.7% and 0.63, respectively. Poor differentiation of the tumor, invasion in lamina propria, lymphatic and blood vessels occurred much more frequently in patients with aneuploid tumors which appeared to indicate high-grade malignant potential of such tumors. It is concluded that DNA content in bladder cancer is a valuable prognostic criterium. This biological marker requires further studies. PMID- 7871624 TI - [Endolymphatic chemotherapy and immunocorrection in patients with kidney and bladder cancers]. AB - Immunological examination and endolymphatic treatment were performed in 44 patients with cancer of the kidney or urinary bladder. In the majority of patients lymphocytes of the peripheral blood demonstrated reduced expression of some differential antigens. Subpopulation of T-lymphocytes, expression of T lymphocyte receptors got decreased in almost all the patients. Endolymphatic introduction of immunocorrective thymalin improved the patients' life quality, their immune status. However, the level and proportional expression of differential lymphocyte antigens following course polychemotherapy and immunocorrection in patients do not coincide with relevant parameters of healthy subjects. It is evident that further search for optimal treatment schemes is needed. PMID- 7871625 TI - [The intraoperative ultrasonic control of the radicalness of transurethral resection in bladder cancer]. AB - 72 patients with bladder cancer stage T1, T2 underwent transurethral resection of the bladder wall affected with tumor under ultrasound control of the removal radicality. The evidence obtained at transurethral ultrasound scanning was compared to the findings of histological examination of the tissue removed. The accuracy of the control made up 87.3%. This made it possible to follow tumor invasion from the tumor margins along the periphery in accordance with blastomatosis stage. The authors have developed a technique of transurethral resection of bladder wall under transurethral ultrasonic scanning as control of the removal radicality. PMID- 7871626 TI - [The surgical treatment of hypospadias using the CO2 laser]. AB - The paper presents the results of plastic reconstruction of the urethra using local tissues according to Browne, Duplay, Cecil as well as CO2-laser scalpel technique. Altogether 140 patients underwent operations, the majority of whom were boys aged 1.5-13 years (87.1%). The authors employed preoperative correction of reactivity disorders found in the above patients which included stimulation of leukopoiesis, activation of phagocytosis. Good immediate results of CO2-laser procedures are attributed to complete hemostasis achieved at dissection of the flap, sterility of the operative area and thermal factor able to reduce the duration and traumatic damage of the interventions. The authors support two-stage approach to correction of the urethral defect. Uneventful developments after operative establishment of the urethra depend on creation of urine bypass by means of epicystostomy. Longterm results were followed up in 70 patients, of whom 55 had good outcomes and 15 satisfactory. No failures occurred. PMID- 7871627 TI - [Acute postoperative gastroduodenal ulcers in urologic patients]. PMID- 7871628 TI - [The formalized diagnosis of acute suppurative pyelonephritis]. AB - Using mathematical analysis methods, the authors try to develop algorithm of the diagnosis and early treatment of acute purulent pyelonephritis (APP). On the basis of 107 case histories (84 surgical, 12 conservative APP cases, 11 patients without the inflammation) characteristic symptoms were established. These may serve as parameters for the classification analysis and plotting curves indicative of the kidney involvement in the pyodestructive process. The analysis of the curves elicited that the pattern of the parameter changes reflects stages of purulent pyelonephritis in the kidney. PMID- 7871629 TI - Madin-Darby canine kidney cells are injured by exposure to oxalate and to calcium oxalate crystals. AB - The reaction of Madin-Darby canine kidney cells (MDCK) to potassium oxalate (KOx), calcium oxalate monohydrate (COM) crystals, or a combination of the two was studied. The most noticeable effect of exposure of the cells to either KOx or COM crystals was loss of cells from the monolayer ranging from 20% to 30%, depending upon the particular treatment. Cellular enzyme values in the media were elevated significantly by 12 h of exposure, although in specific instances, elevated levels occurred at earlier time periods. As regards the monolayer, trypan blue exclusion was decreased significantly, although amounting to only a 4 5% reduction. Specific tritiated release occurred at 4 and 12 h after exposure to KOx and at 12 h after exposure to crystals. Structurally, COM-cell interactions were complex and extensive endocytosis was noted. Cells were released from culture either as cell-crystal complexes or from the intercellular spaces after exocytosis. When treatments were combined the effects were only slightly additive, but the two treatments potentiated each other: all media enzyme levels (with one exception) were elevated at 2 h, tritiated adenine release was present at 4 h, and there was more extensive cell loss from the culture monolayer. These data suggest that both KOx and COM crystals damage MDCK cells when applied alone, and in concert they act synergistically. PMID- 7871630 TI - The effect of vesical outlet obstruction on the protein secondary structure of the mucosa and serosa in rabbit bladder wall. AB - The biochemical composition of physiologically moist mucosa and serosa of rabbit bladder before and after bladder outlet obstruction was determined by means of FT IR spectroscopy with the ATR method and second-derivative analysis. A predominantly beta-sheet structure was found in the amide I band for mucosa and serosa before and after obstruction, but the random coil structure increased in both obstructed bladder samples. However, the major beta-sheet structure associated with some alpha-helical structure in the amide II band of mucosa and serosa for non-obstructed bladder changed into a predominantly alpha-helical structure after bladder obstruction. The obstructed bladder serosa was more pronounced. The amount of glycoproteins doubled in the obstructed bladder serosa, but did not change in the bladder mucosa. PMID- 7871631 TI - Magnetic resonance imaging of urinary calculi. AB - Accurate prediction of the response of an individual patient to lithotripsy remains impossible. Certain factors such as the chemical composition, size, and position of the calculus are known to be important in determining the success rate. This paper reports the use of magnetic resonance imaging (MRI) to evaluate 141 urinary calculi in vitro. A wide range of signals for each chemical type of calculus was found on each of the three imaging sequences used (T1-weighted, T2 weighted, and proton density). None of the chemical groups examined showed a typical MRI profile allowing it to be distinguished from the other groups. Analysis of variance showed a statistical difference between signals for apatite and struvite on the T1-weighted sequence, and between struvite and uric acid on the proton density sequence (both, P < 0.05). These results show for the first time that MRI is capable of distinguishing between different chemical types of stones. This is particularly important for the comparison of struvite and apatite which appear to be similar in conventional investigations but have quite different hardness values. Further work is in progress correlating the results of this study with stone microhardness and extracorporeal shockwave lithotripsy fragility tests to determine whether MRI accurately predicts the success of lithotripsy. PMID- 7871632 TI - Quantitative DNA measurement by flow cytometry and image analysis of human nonseminomatous germ cell testicular tumors. AB - Current clinical staging, which includes the use of serum tumor markers and imaging techniques, fails to identify the 30-40% of clinical stage I (CS I) nonseminomatous germ cell testicular tumor (NSGCT) patients who have occult metastatic disease. Therefore, there is a real clinical need to evaluate new biological parameters of the primary tumor that might be useful as predictors of occult metastatic disease. This study was undertaken to compare quantitative DNA measurements by flow cytometry and image analysis in CS I NSGCT, and to analyze the relevance of these parameters for predicting occult lymph node involvement. Different blocks of formalin-fixed, paraffin-embedded NSGCTs of 62 CS I patients who underwent retroperitoneal lymph node dissection between 1985 and 1989 were prepared according to the Hedley technique, and analyzed by quantitative cytometry. Thirty-six (58.1%) patients had histologically proven lymph node involvement (pathological stage II), whereas 26 (41.9%) patients (pathological stage I) had neither lymph node metastases according to retroperitoneal lymph node dissection (RPLND) specimens nor tumor recurrence during follow-up. Concordant results were found in 76.5% of the samples by both cytometric techniques. For flow cytometry, the percentages of aneuploid cells in the S- and the G2M + S-phase were the most robust predictive parameters for lymph node involvement, whereas for image analysis the 5c exceeding rate (5cER) had the most predictive significance. Based on the experience obtained in this study, both cytometric techniques provide additional information on tumor aggressiveness that might be useful in therapeutic selection of early stage NSGCT patients for either RPLND or surveillance only. PMID- 7871633 TI - An assessment of immunoreactive epidermal growth factor in urine of patients with urological diseases. AB - To examine the excretion of urinary epidermal growth factor (EGF) in urological diseases and the relationship of EGF urine levels with transitional cell carcinoma (TCC), we measured the concentration of EGF by radioimmunoassay. The series comprised patients with active TCC (n = 52), others in tumor-free status (n = 29) and with non-neoplastic inflammatory diseases (n = 43), and normal controls (n = 50). Urinary EGF values were lower in patients with urological diseases of different etiologies than in normal controls (P < 0.005). Mean EGF levels of patients who had previous bladder tumor resection (n = 21) were not statistically different from normal controls (P = 0.2). For patients with active TCC, EGF urine levels showed a significant inverse relationship to increasing tumor grade (P = 0.02). In addition, subjects who had received nephrectomy for pelvic carcinoma (n = 8) showed significantly lower mean EGF values than those with intact kidneys (n = 21), irrespective of sex (P < 0.05). Immunostaining of EGF on non-neoplastic kidney (n = 9) revealed reactivity in the distal convoluted tubules and thick ascending limbs of Henle. Our results suggest that the kidney is the major source of urinary EGF. Its excretion in urine is decreased in both inflammatory and neoplastic diseases of the urinary tract. EGF may play an important part in the biological activity of TCC. Further study is indicated to investigate the monitoring of EGF urine levels as a marker of recurrence for EGF receptor-positive TCC. PMID- 7871634 TI - Evening primrose oil reduces urinary calcium excretion in both normal and hypercalciuric rats. AB - Hypercalciuria is an important risk factor in the aetiology of idiopathic urolithiasis and many treatment modalities in clinical practice are directed towards reducing urinary calcium excretion. There are no natural animal models of hypercalciuria, such as the spontaneous hypertensive rat; however, the streptozotocin-diabetic rat is accepted as a good model for studies of disordered renal function associated with diabetes mellitus. Hypercalciuria is a prominent feature of the streptozotocin-diabetic rat and the model was, therefore, used to study the influence of evening primrose oil on urinary calcium excretion. Twenty rats divided into two groups of ten rats each were maintained on either normal rat chow (group 1) or primrose oil enriched diet (group 2) for 10 weeks. At 4 weeks both groups of rats were made diabetic with streptozotocin. Urine calcium measurements were serially performed before commencement of the diet, during the pre-streptozotocin (pre-diabetic) phase and during the post streptozotocin (diabetic) phase. The urine calcium excretion was significantly less in the primrose oil fed animals during both the pre-diabetic phase and the diabetic phase compared with the rats on the normal rat chow. These results indicate that evening primrose oil, a rich source of gamma-linolenic acid, helps to reduce urine calcium excretion in normal animals as well as in the hypercalciuric streptozotocin-diabetic rat. Dietary modifications with long-chain omega-6 and omega-3 fatty acids might be a useful adjunct in the treatment of idiopathic hypercalciuric urolithiasis. PMID- 7871635 TI - Relationship between renal capsular artery feeding and size of VX-2 carcinoma implant in the rabbit kidney. AB - When regional intraarterial infusion is applied in the treatment of malignant tumors it is essential to reach the tumor via all its major feeder vessels. In this study VX-2 carcinoma was implanted into the lower pole of the left kidney in 24 rabbits to investigate whether the renal capsular artery takes part in tumor feeding. The rabbits were divided into four groups that were followed for 8, 10, 12 or 14 days after tumor implantation. At that time the renal artery was ligated close to the kidney and subsequently silicone rubber on barium sulfate/gelatin suspension was injected into the capsular artery. The tissue was cleared, and the tumor carefully removed and examined microscopically for traces of silicone rubber. When barium sulfate had been injected, the kidney was examined radiographically in order to detect possible presence of contrast medium in the tumor. This study revealed no vascular supply to the implanted VX-2 carcinoma from the capsular artery when the tumor was confined intracapsularly, i.e., up to 12 days after tumor implantation in untreated rabbits. PMID- 7871636 TI - Long-term changes in urodynamic studies of voiding in the elderly. AB - Urodynamic studies were conducted in 80 incontinent elderly patients (27 men and 53 women; mean age, 77 years) and repeated 2-4 weeks later after patients had been subject to interventions. Interpretable voiding studies were performed in 84% of sessions. Interpretable initial and repeat studies were performed in 74% of patients. For detrusor pressure at maximum flow the intra-individual, between sessions variability was +/- 11.7 cm H2O (SD) and the initial-repeat correlation coefficient was 0.61. For maximum flow rate the corresponding figures were +/- 4.7 ml/s and 0.44. Mean residual urine volume was 195 ml, with a between-sessions variability of +/- 113 ml (SD). These results suggest that there is substantial long-term variability in voiding function, including urethral resistance. Of the mean, 5% showed a change in obstruction classification (unobstructed/obstructed) between sessions. This variability and the modest proportion of interpretable studies should be taken into account when assessing urethral obstruction and designing clinical trials. PMID- 7871637 TI - Effects of sequential intravesical administration of mitomycin C and bacillus Calmette-Guerin on the immune response in the guinea pig bladder. AB - It has been suggested that intravesical treatment with mitomycin C (MMC) before instillation of bacillus Calmette-Guerin (BCG) improves the antitumor activity of BCG in human bladder cancer. Therefore, we studied the immunological effects of sequential intravesical treatment with MMC and BCG in the guinea pig. Four weekly intravesical instillations with MMC preceded six weekly intravesical BCG instillations. The delayed-type hypersensitivity (DTH) skin reaction evoked by tuberculin purified protein derivative (PPD) in guinea pigs receiving BCG intravesically appeared slightly earlier in animals pretreated intravesically with MMC than in phosphate-buffered saline (PBS)-pretreated animals. However, after completing BCG instillations no differences in DTH reaction were observed between these treatment groups. The extent of the local inflammatory reaction in the bladder wall, as well as the parameters measured in the draining iliacal lymph nodes (i.e., the weight, the number of leukocytes, and the composition of leukocyte subpopulations), did not differ in animals treated with BCG alone or in combination with MMC. A slight increase in the MHC class II expression on the bladder urothelium was shown if MMC and BCG treatment was combined. The adherence of mycobacteria to the bladder wall, measured using 3H-labeled mycobacteria, dit not differ between MMC/BCG- and BCG-treated animals. We conclude that MMC does not enhance the immune response against mycobacteria. Therefore, we hypothesize that a possible increased antitumor activity by the combination of MMC and BCG might be due to separate, rather than synergistic, effects of the drugs, namely a cytostatic effect of MMC on tumor cells and a local immune response in the bladder evoked by BCG. PMID- 7871638 TI - Cytotoxic effects of alpha- and gamma-interferon and tumor necrosis factor in human bladder tumor cell lines. AB - We investigated the activity of alpha-interferon (alpha-IFN), gamma-interferon (gamma-IFN) and tumor necrosis factor-alpha (TNF-alpha) in a panel of ten human bladder tumor cell lines. All cytokines were tested at concentrations of 100 10,000 U/ml in a clonogenic assay system. We found that alpha-IFN was active against five of the ten lines while gamma-IFN was only active against one line. TNF was active against five of the ten lines. Maximum synergisms were obtained between the alpha-IFN and TNF, occurring in nine of the ten cell lines. We conclude that alpha-IFN and TNF are active as single agents and synergistic when used together in vitro in human bladder tumor cell lines. PMID- 7871639 TI - Elevated concentrations of the beta-subunit of S100 protein in renal cell tumors in rats. AB - Concentrations of alpha and beta-subunits of S100 protein (S100-alpha and S100 beta) in rat kidney neoplasms, including renal cell and mesenchymal tumors, were determined using a highly sensitive enzyme immunoassay, and both types immunohistochemically localized in tissue sections. Concentrations of S100-alpha in each histological type of rat tumor were lower than in normal kidney, whereas levels of S100-beta (mean +/- SE: 29.7 +/- 14.2 ng/mg protein, n = 15) in renal cell tumors were significantly higher than in normal kidneys (0.55 +/- 0.06 ng/mg protein, n = 7), or mesenchymal tumors (1.21 +/- 0.43 ng/mg protein, n = 9). In normal rat kidney tissues S100-alpha was immunohistochemically positive in epithelial cells of the distal tubules, the thin limbs of loops of Henle, and the collecting ducts. No appreciable immunostaining for S100-beta was found in any nephron segment. Both S100-alpha and S100-beta were positive for renal cell tumors, indicating new appearance of the latter during renal carcinogenesis in rats. PMID- 7871640 TI - Reduced inhibitory activity of uronic-acid-rich protein in urine of stone formers. AB - We recently reported that human urine contains a newly identified urinary glycoprotein acting as a potent inhibitor against calcium oxalate crystallization. This inhibitor is a uronic-acid-rich protein (UAP) with a molecular weight of approximately 35 kDa. In the present study, UAP was isolated from urine of stone formers and of subjects without a stone history, and its inhibitory activity was tested in a calcium oxalate crystallization system in vitro. Our results show a weaker inhibitory activity of UAP extracted from the urine of stone formers than that extracted from the urine of healthy subjects. Preliminary analyses of amino acid and carbohydrate content showed some differences between the two groups. The main difference was the reduction in sialic acid in UAP isolated from the urine of stone formers. We suggest that UAP contributes significantly to total urinary inhibitory activity of calcium oxalate crystallization and that the decrease in this activity in the urine of recurrent stone formers is due, in part, to the weak inhibitory activity of UAP. A structural abnormality of UAP could explain the diminution of its inhibitory activity in the urine of stone formers. PMID- 7871641 TI - Cytotoxic effect of diphtheria toxin used alone or in combination with other agents on human renal cell carcinoma cell lines. AB - Treatment of renal cell carcinoma (RCC) by conventional chemotherapy and immunotherapy has resulted in minimal remissions. Alternative forms of therapy are therefore being sought. The present study investigated the sensitivity of RCC cell lines to several toxins used alone and in combination with other agents. RCC lines were relatively sensitive to the direct cytotoxic effect of diphtheria toxin (DTX), Pseudomonas aeruginosa exotoxin A (PEA) and ricin. Furthermore, DTX in combination with tumor necrosis factor-alpha (TNF-alpha) resulted in synergistic cytotoxic activity. The mechanism of synergy was examined. A possible mechanism of resistance to TNF-alpha in tumor cells is the expression of TNF alpha mRNA or protein. R11 cells did not constitutively express mRNA for TNF alpha, however, treatment of R11 cells with TNF-alpha induced the expression of TNF-alpha mRNA. When DTX was used in combination with TNF-alpha, the level of TNF alpha mRNA induced by TNF-alpha was markedly reduced. These studies suggest that DTX in combination with TNF-alpha can overcome the resistance of RCC lines and that the marked downregulation of TNF-alpha mRNA by DTX may play a role in the enhanced cytotoxicity seen with the combination of DTX and TNF-alpha. Furthermore, the combination treatment might also potentiate the antitumor host responses. The implications of these findings in clinical therapy are discussed. PMID- 7871642 TI - [Role of the size and shape of the eye in the course of diabetic retinopathy]. AB - Sixty-nine patients with diabetes mellitus were examined to elucidate the role of the size and shape of eyes in the course of diabetic retinopathy. Diabetic changes in the eyes were two times less incident in the patients whose mean size of the eyes was more than 24 mm than in those with eyes of less than 24 mm in diameter. Proliferative retinopathy was never detected in the eyes with a mean size of at least 25 mm. A larger eye is an independent factor which has a positive impact on the course of diabetic retinopathy. PMID- 7871643 TI - [Surgical treatment of strabismus with superior oblique muscle insufficiency]. PMID- 7871644 TI - [The Pau phenomenon and complex movements of hyaloid in aphakic eyes]. AB - The author analyzed complex movements of the hyaloid at the height of the ciliary muscle contraction in 121 aphakic eyes. He came to a conclusion that hyaloid dislocation is an active process realized by the ciliary muscle in the course of its contraction. Hyaloid and the vascular coating, on the one hand, and the ciliary muscle, on the other, were shown to be antagonists. Atropine in instillations paralysed the whole muscle, and it was impossible then to detect the predominance of Brucke's muscle over Muller's one. Adrenalin instillations after Gredle or subconjunctivally did not stimulate the contractions of Brucke's muscle, but only those of the vascular coating, for the effects of adrenalin on vascular walls are well known. As for the double innervation of accommodation, it is a fact undeniable, which only confirms that sympathetic innervation performs a trophic function in any tissue, and in the ciliary muscle as well as anywhere else. PMID- 7871645 TI - [Pseudodysfunction of oblique muscles]. AB - The authors offer a hypothesis on the possibility of development of vertical components of deviation in concomitant eso- or exotropia as a result of specific functioning of horizontal muscles in subjects with oblique palpebral fissure. Such a vertical deviation clinically corresponds to dysfunction (imbalance) of oblique muscles in its symmetrical variant and is therefore termed by the authors "pseudodysfunction of oblique muscles". Differential diagnostic basis for differentiation between true and false dysfunction of oblique muscles in concomitant strabismus is formulated. PMID- 7871646 TI - [Changes in clinical refraction in future pilots during the course of training]. AB - Changes in clinical refraction parameters were followed up in 343 students of school of pilots in the town of Burguruslan in the course of vocational training. Skiascopy and laser refractometry methods were used. Dynamic follow-up of clinical refraction showed its increase in 24.3% of the examinees both with emmetropia and hypertropia or myopia. The most noticeable increase of refraction was observed during the first two years of training, which may be explained by intensive exercise of the eyes because of theoretical studies and flights. The results evidence practical advantages of laser refractometry in comparison with skiascopy. PMID- 7871647 TI - [Study of lacrimal fluid trace elements in several eye diseases]. AB - Trace element composition and content were studied by neutron activation method and atomic emission spectral analysis in 200 lacrimal fluid samples from children and adolescents with emmetropia and progressive myopia of 3.5 to 12.0 diopters and in 48 samples from adults with open-angle glaucoma, diabetic retinopathy, and without ocular diseases (controls). Lacrimal fluid trace element level reflecting their metabolism in the eye was found related to subjects' age and sex and changed in various diseases. Progressive myopia was found associated with reduced cooper content and changed ratio of zinc to iron, this indicating certain metabolic disorders in the connective tissue system, in the scleral membrane first of all, and in the antioxidant defense system. Changed levels of iron, magnesium, and aluminum were detected, and, to a lesser extent, of zinc and copper in patients with diabetic retinopathy, whereas open-angle glaucoma was associated with reduced zinc level and increased iron content. PMID- 7871648 TI - [Clinical and immunological signs of retinal lesions and possibilities of their correction by drugs in patients with chronic diffuse liver diseases of viral etiology and carriers of Australia antigen]. AB - A total of 133 subjects aged 15 to 55 were followed up, the main group (n = 87), patients with chronic diffuse diseases of the liver caused by hepatitis B virus, and two reference groups, 26 patients with uveitis and 20 normal subjects, 13 and 4 subjects of each group, respectively, were Australian antigen (HBsAg) carriers. Functional disorders of the retina were detected in 93.2% of group 1 patients, as well as intensified local (tears) and total system (blood) autoimmune reactions to tissue-specific retinal S-antigen (mol.mass 48 kD). An increased detection rate of antibodies to S-antigen and its higher titers were found in healthy virus carriers as compared to HBsAg-seronegative donors. These data may be regarded as evidence of an increased risk of uveoretinal pathology in subjects infected with hepatitis B virus, this being confirmed by a higher incidence (50%) of latent virus carriership in the group of patients with uveoretinitis. Stabilizing effect of cavinton in functional changes of the retina was revealed, this recommending this drug for combined therapy of patients with chronic diffuse diseases of the liver and for prevention of ocular diseases. The majority of the examinees in whom retinal abnormalities were found being young, the authors draw attention to the social aspect of the problem. PMID- 7871649 TI - [Effects of protein S-100 beta on the course of corneal healing in rabbits]. AB - Effects of S-100 beta protein on wound healing in rabbit eye cornea were studied. A subconjunctival injection of the protein was found to lead to earlier epithelialization, decrease of the index of migrating inflammation cells, and prevention of fibrous subepithelial growth. Hence, administration of S-100 beta protein resulted in a more effective and rapid healing of the cornea. PMID- 7871650 TI - [Ophthalmological symptoms in patients with internal carotid artery pathology]. AB - Ophthalmologic examinations were carried out in 92 patients, mean age 55.4 years, with internal carotid artery abnormalities (stenoses and thromboses) confirmed by dopplerography. Various visual disturbances were diagnosed, the most prevalent ocular symptom being transitory homolateral blindness which was detected in 28 (30.4%) patients. Optic disk abnormalities were found in 9 (9.8%) patients, thrombosis (embolism) of the central retinal artery or its branch in 3 (3.3%); 6(6.5%) patients developed monolateral retinopathy which resulted from persistent retinal hypoxemia, and only 1 (1.1%) patient presented with ischemic oculopathy. Later developing neurologic and ophthalmologic complications may be prevented if visual disturbances of this type, particularly transitory ones, are not neglected during diagnosis of carotid diseases. PMID- 7871651 TI - [Pathology of the eye in sarcoidosis]. AB - Comprehensive neurologic and ophthalmologic examinations of 100 patients with morphologically verified sarcoidosis showed the most frequent involvement of optic nerves and less incident lesions of the eye proper and its appendages. Vision disorders were detected in 39.0 patients, chiasmal disorders in 12.0%. Fundus oculi abnormalities were found in 27.0% of patients. A specific feature of vision disorders in sarcoidosis was that almost half of the patients did not feel them, which may be explained by a predominantly chronic latent pattern of these disorders and by the fact that, despite manifest disorders of peripheral vision, central vision with correction remained normal for a longer time. PMID- 7871652 TI - [Short-term safe mydriasis in the diagnosis of glaucoma]. PMID- 7871653 TI - [Clinical aspects and treatment of herpes virus lesions of the eye in human immunodeficiency virus (HIV) infection]. PMID- 7871654 TI - [Clinical aspects of the use of contact lenses in ophthalmology]. PMID- 7871655 TI - [Results of pikamilon use in the treatment of patients with open-angle glaucoma]. AB - Administration of pikamilon, a cerebrovascular and nootropic drug, to patients with primary open-angle glaucoma with normalized intraocular pressure and declining visual function resulted in improvement of the central and peripheral visual fields manifesting by improvement of individual sensitivity threshold, decreased area and intensity of scotomas; the treatment had a favorable effect on light sensitivity and vision acuity in some patients. No noticeable effect on arterial pressure was observed. The drug did not reduce the intraocular pressure. PMID- 7871656 TI - [Role of local factors in the pathogenesis of diabetic retinopathy]. AB - The pathogenesis of diabetic retinopathy includes the following components actual at a local level: diffuse retinal hypoxia leading to increase in the retina of anaerobic energy processes, development of local acidosis causing venous congestion, increased permeability of retinal capillaries and veins, impairment of the structure of vascular walls, development of foci of deep retinal hypoxia and of proliferative changes. These disorders develop in succession and mutually aggravate each other. A noticeable role belongs to deteriorated evacuation of the products of abnormal metabolism which depends on the existence of a solid barrier (pigmented epithelium, Bruch's membrane) between the retina and choroid and on the venous congestion and impaired liquid circulation in the vitreous body. A dichotomic type of division of the central retinal artery and absence of anastomoses between its branches facilitate the appearance of foci of retinal hypoxia. Local pathogenetic therapy of diabetic retinopathy should be aimed at removal of at least one out of three factors: hypoxia, acidosis, or venous congestion. This does not make less important the treatment of general metabolic disorders characteristic of diabetes mellitus. PMID- 7871657 TI - [Autonomic nervous system in patients with cochleovestibular diseases]. AB - Clinical, electrophysiological investigations, evaluation of autonomic nervous system reactivity with estimation of Kerdo vegetative and stability indices were carried out in 58 patients with cochleovestibulopathy (CVP) and 10 normal controls. CVP patients with compensated disease had sympathicotonia, those with decompensated CVP exhibited parasympathicotonia. Functional loading tests and the stability index values revealed compensatory nature of sympathicotonia. Quantitative and qualitative characteristics of the compensation were related to age (under 40, over 41) and pathogenesis of the disease (central or peripheral). In CVP decompensation poor tolerance of mental work load was reported. PMID- 7871658 TI - [Diagnosis of peripheral diseases of the facial nerve]. AB - Work-up of 120 patients with peripheral facial paresis included evaluation of spontaneous and reflex lacrimal secretion, electrogustometry, impedance, tonal and supraliminal tonal audiometry. Symptom complexes for different by severity nerve lesions are specified. In patients with basilar skull fractures 3 types of postdenervation syndromes were observed: atropine salivary paradox, paradoxical facial hyperemia, crocodile tears. A scheme of topical diagnosis is presented. PMID- 7871659 TI - [Kinematics of the ear ossicles]. AB - The paper details the movements of the auditory ossicula in exposure to low- and high-frequency sounds. Low-frequency sound causes the hammer to vibrate along the line crossing the tympanic anterior and posterior folds. Because of the screw shape of the anvil-hammer junction these hammer movements produce dislocation of the long anvil process along the base of the stapes. Due to the spherical shape of the anvil-stapes junction the above shift gives rise to pedal movements of the base of the stapes by the transverse short axis of the vertibular window. High frequency sound waves are transmitted by the crest from the walls of the middle ear cavity to the short hammer process. This produces its rotation responsible for the anvil long process shift across the vestibular window, up and down. These vibrations result in vibrations of the base of the stapes crosswise the vestibular window. PMID- 7871660 TI - [Contact laser surgery in the treatment of laryngeal neoplasms]. AB - YAG-ND laser contact surgery in combination with tracheal puncture jet ventilation of the lungs were used in managing 128 patients with laryngeal cancer (T1-T2) and 129 patients with benign lesions of the larynx. A complete response was achieved in 97.3% of stage I and 94.4% of cancer stage II patients. The recurrences occurred in 7 out of 129 patients with benign lesions. PMID- 7871661 TI - [Diffuse sympathetic block in the intensive therapy of pharyngeal and esophageal chemical burns]. AB - The course of inflammation was followed up during combined treatment of 50 patients with pharyngeal and esophageal chemical burns. The treatment scheme included sympathetic block comprising subpleural and stallate ganglion blocks. Compared to controls, the test subjects showed more rapid control of inflammation proved by a positive clinical pattern, reduction of local processes, absence of intoxication. Thermometry and thermography in the block zone evidenced improved microcirculation, probably, due to vegetative responses. The latter are suggested to be the mechanism of the block action which reestablished normal trophism of the affected tissue. Enteral feeding initiated early after pain relief promoted repair processes leading to stable levels of total protein, electrolytes, blood sugar. The above measures make it possible to initiate early bouginage the performance of which becomes painless with good outcomes (no esophageal stenosis, earlier discharge from hospital). PMID- 7871662 TI - [Vascular neoplasms of the larynx, pharynx, and mouth cavity in children]. AB - 41 children with vascular tumors of the larynx, pharynx and mouth cavity were examined in the hospital. Hemangiomas were found in 29, lymphangiomas in 11 cases, lymphemangioma in one child. The tumors had multiple location and in 22 patients were combined with dermal angiomatosis. The chief techniques of removing the above vascular tumors were cryosurgery and CO2-laser coagulation. Radiotherapy was applied in cases of extensive dermal angiomatosis. A good response was achieved in 37 cases, tumor growth persisted in one patient. One child died as a result of the disease progression, and one more child of an intercurrent disease. PMID- 7871663 TI - [Problems of combined surgeries in otorhinolaryngologic practice]. AB - Long-term experience gained by the author in combined ENT surgery has convinced him of the benefit which may be obtained from wider introduction of combined surgical treatment of patients suffering from combined lesions of the upper air ways. Discussion of clinical and diagnostic approaches, preoperative preparation of patients, choice of anesthesia for such patients promotes the solution of the tasks of great clinical significance. PMID- 7871664 TI - [Pharmacologic therapy in pharyngitis]. AB - The authors review general principles guiding chemotherapy of acute and chronic pharyngitis. Drugs are listed which are thought the best for each particular form of pharyngitis. PMID- 7871665 TI - [Closed rhinoplasty ]. PMID- 7871666 TI - [Acne rosacea complicated with demodicosis]. AB - Demodicosis caused by infestation with Demodex folliculorum hominis is a parasitic acariasis disease which may affect nasal skin. Acne rosacea with demodicosis must be distinguished from nasal furunculi which require antiinflammatory, hyposensitizing treatment. If the latter fails, it is acna rosacea with demodicosis that must be suspected. The diagnosis is made by investigation of nasal skin scrapings. If the mites are found, the patient should be referred to dermatologist for specific treatment. PMID- 7871667 TI - [Malherbe's epithelioma of the preauricular region]. PMID- 7871668 TI - [A case of external cervical fibroma]. PMID- 7871669 TI - [Chronic foreign bodies in the nasal cavity in children]. PMID- 7871670 TI - [Significance of dynamic measurements of acoustic impedance for early detection of hypoesthesia in otosclerosis]. AB - To clarify the role of dynamic registration of acoustic impedance in early detection of hypoacusis in otosclerosis, the authors analyzed impedometry readings in subjects with unilateral otosclerosis. Special emphasis is laid on cases with minor audiogram bone-air intervals. Based on comparison of contra- and ipsilateral reflexes, registration of the acoustic reflex may provide early signs of otosclerosis. PMID- 7871671 TI - Conservation highlighted at Durban congress. PMID- 7871672 TI - Comparison of ultrasonographic and radiographic findings in cows with traumatic reticuloperitonitis. AB - The radiographic and ultrasonographic findings in 26 cows with traumatic reticuloperitonitis were compared. The cows were divided into three groups based on the radiographic findings; the first group consisted of 12 cows in which the principal radiographic finding was a foreign body penetrating the reticulum; the second group contained four cows in which the principal radiographic finding was gas shadows or a gas-fluid interface, the third group consisted of 10 cows that had no reliable radiographic evidence of traumatic reticuloperitonitis, such as an abnormal contour, position or shape of the reticulum. In no case could the foreign bodies be visualised by ultrasonography. In all the cows except one with radiographic evidence of abnormal gas inclusions and gas-fluid interfaces, ultrasonography revealed echogenic, partitioned and capsulated structures with central hypoechogenic cavities. In addition, in some of the cows with no radiographic evidence of the condition, severe changes indicative of inflammatory processes were visible by ultrasonography. PMID- 7871673 TI - Mastitis incidence in low cell count herds. PMID- 7871674 TI - Tubal transfer of goat embryos using endoscopy. PMID- 7871675 TI - Flaccid oesophageal paralysis in a Friesian heifer associated with encephalitis. PMID- 7871676 TI - Obstipation secondary to coccygeal vertebral separation in a cat. PMID- 7871677 TI - Future of the State Veterinary Service. PMID- 7871678 TI - Future of the State Veterinary Service. PMID- 7871679 TI - Veterinary nursing examinations. PMID- 7871680 TI - Veterinary nursing examinations. PMID- 7871681 TI - Normal bat flora. PMID- 7871682 TI - 'Flying scapulas' and the perils of exercise. PMID- 7871683 TI - Pig housing. PMID- 7871684 TI - Spongiform encephalopathies in zoo animals. PMID- 7871686 TI - EU divide bedevils transport issue. PMID- 7871685 TI - TB vaccine for badgers. PMID- 7871687 TI - Communication with a capital 'C'. PMID- 7871688 TI - Possible origin of rabbit haemorrhagic disease in the United Kingdom. AB - Rabbit haemorrhagic disease was reported for the first time in the United Kingdom in 1992, and there followed four further small localised outbreaks, all in the south of England. Investigation has revealed no definitive mechanism for the introduction of the disease but it is considered that it probably originated from the near continent. The possibility of the transmission of the virus across the Channel by aerosol, birds and south coast ferry traffic is discussed, particularly with respect to the 1993 outbreaks of the disease in Kent and East Sussex. There may be implications for infection of wild rabbits, although preliminary investigation has shown no direct evidence of the disease in them. PMID- 7871689 TI - Plasma beta-endorphin response of thoroughbred horses to maximal exercise. AB - Ten horses underwent a standardised strenuous treadmill exercise test, before, during and after which measurements were made of plasma beta-endorphin and cortisol concentrations, blood lactate, glucose, haemoglobin and pH, the activities of creatine kinase, lactate dehydrogenase and aspartate amino transferase, and heart rate, oxygen uptake and expired minute volume. The correlations between the exercise-induced response of beta-endorphin and the changes observed in the other physiological measurements were examined. There was a large variation in the beta-endorphin response of the horses to exercise. The increase in beta-endorphin was correlated significantly and inversely with the treadmill velocity at which maximal oxygen uptake was reached. It was also significantly and directly correlated with the heart rate during recovery, the increase in plasma lactate concentration and the change in blood pH, indicating that the exercise-induced increase in beta-endorphin concentration was smaller in horses with a higher aerobic capacity. PMID- 7871690 TI - Nematode burdens and productivity of grazing cattle treated with a prototype sustained-release bolus containing ivermectin. AB - One hundred and twenty four-month-old Hereford-Friesian cross heifers weighing from 88 to 130 kg were divided into two equal groups. One group acted as a control with each animal receiving one placebo bolus, the other animals received one prototype intraruminal sustained-release bolus designed to deliver approximately 8 mg ivermectin/day for 100 to 120 days. The boluses were administered the day before turnout in mid-May. Each group was grazed separately for 167 days on pastures contaminated with parasitic nematode larvae including the lungworm Dictyocaulus viviparus, and the gastrointestinal worms Ostertagia ostertagi, Cooperia oncophora and Nematodirus helvetianus. Parasitic disease did not occur in the ivermectin-bolus group, but the control group required anthelmintic treatment to control parasitic gastroenteritis at 111 and 154 days after turnout. Up to the 111th day after turnout, the peak mean nematode egg and larval counts per gram of faeces in controls was, respectively, 564 epg and 0.5 lpg. Based on faecal nematode egg counts and worm burdens in bolus-treated cattle removed from pasture at 119 days after turnout and bolus function studies, it was concluded that ivermectin delivery from the prototype bolus ceased between 95 and 98 days after administration. However, unlike the controls, the treated cattle did not develop parasitic gastroenteritis at any time. Their faecal nematode egg output was significantly (P < 0.01) lower (< 1 epg) compared to the controls and lungworm larval output zero during the functional life of the bolus. The faecal egg and larval outputs continued low until the end of the trial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871691 TI - Seroprevalence and isolation rate of Bordetella bronchiseptica in cats in the UK. PMID- 7871693 TI - Future of the State Veterinary Service. PMID- 7871692 TI - Exercise induced hyperthermia in a racing greyhound. PMID- 7871694 TI - Progestins in dogs. PMID- 7871695 TI - Stone swallowing. PMID- 7871696 TI - Effect of climatic stress on the immunological reactivity of weaned pigs. AB - Weaned pigs exposed daily to either unpredictable draught (experiment 1) or intermittent unpredictable draught (experiment 2) showed different lymphocyte blastogenic responses after mitogenic stimulation with phytohaemagglutinin (PHA) and concanavalin A (ConA). In both experiments PHA skin test responses were lower for draught exposed pigs than for control pigs and leucocyte numbers or profiles were altered compared to those of control pigs. Superoxide production and chemiluminescence of porcine granulocytes were similar for draught exposed and control animals. Furthermore, serum globulin content did not differ significantly between pigs in the experimental and control room. The strong increase in serum gamma-globulin after the Aujeszky Disease Virus (ADV)-challenge was the same for draught exposed and control pigs. The same held for the lymphocyte blastogenic response with ADV protein as antigenic stimulus. The present study shows the effects of climatic stress on immunological reactivity, which may reflect a homeostatic disturbance of the pig's immune system elicited by exposure to unpredictable draught. PMID- 7871697 TI - An experimental field study on the build up of lungworm infections in cattle. AB - The build up of lungworm infections was studied in four groups of calves. Calves of Group 1 were infected experimentally with 6 x 10 larvae during the first 3 weeks after turnout. The pasture of Group 2 was contaminated with approximately 35,000 larvae in June and the pasture of Group 3 with approximately 1.3 million larvae in August. Group 4 served as the helminth free control group for challenge infections with 5,000 larvae in October. In Group 1 faecal larval counts increased 5 weeks after the beginning of patency and decreased after another 3 weeks, indicating the development of immunity after the second lungworm generation. In contrast, the development of immunity in Groups 2 and 3 occurred after the first lungworm generation as maximal faecal larval counts were seen within 3.5 weeks after the beginning of patency. Infection levels were highest in Group 3 which was the only group showing clinical signs. These signs became worse after oxfendazole treatment. PMID- 7871698 TI - Double blind field evaluation of a trivalent vaccine against respiratory disease in veal calves. AB - A field trial was performed to determine the effect of a trivalent vaccine on Clinical Respiratory Tract Problems (CRTP) in veal calves. The vaccine has been developed to increase immunity against the causal agents of IBR, BVD and BRSV infection. In total 928 calves, housed in 16 compartments of one herd, were involved. In four compartments of 58 calves each, vaccinated and non-vaccinated calves were housed together. Four other compartments were treated as a whole and 8 compartments were left untreated. CRTP incidence, medications, weight gain, haemoglobulin and IgG level were recorded. From CRTP positive animals, seroconversion and presence of specific bacteriae and/or viruses were measured as well. Results of the compartments where vaccinated and non-vaccinated calves were housed together showed that the incidence of CRTP in vaccinated calves was 0.16 while it amounted to 0.28 in controls. Most cases were found between day 40 and 60 after the start of the trial. Seroconversion for vaccine specific viruses was sporadically found, but the presence of Pasteurella's was confirmed in the majority of cases. Presumably, the higher incidence of CRTP in the control group was due to a higher level of BVDV infection which might facilitate a clinical infection with Pasteurella's. Vaccination was also negatively related to the percentage of affected lungs at slaughter, the number of days antibiotics had to be administered and subsequently to medicine costs, although these effects were not significant. Daily weight gain was significantly affected by CRTP, but not by vaccination. The effects of vaccination in the compartments where calves were either all vaccinated or not-vaccinated, were similar or larger when compared to the effects in compartments where half of the calves were vaccinated. PMID- 7871699 TI - Establishment of a microbiologically acceptable daily intake of antimicrobial drug residues. AB - A model is presented to calculate the microbiologically acceptable daily intake (ADIm) of antibiotic residues in food products. The ADIm calculation is based on MIC values for indicator bacteria Escherichia coli, Bacteroides fragilis, Bifidobacterium spp. and Eubacterium spp., established under gut-like conditions in an in vitro simulation model. The maximum residue level (MRL) for residues in food products can be derived from the ADIm. Four phases can be distinguished in this gastro-intestinal simulation model, namely: 1. In vitro determination of the MIC for each bacterial strain by a standard method. 2. Incorporation of the drug into food (meat, milk) followed by testing of the stability of the antibiotic under gut-like conditions. 3. Adjustment of the 'gastric' fluid to the duodenal situation, inoculation with the test bacteria and anaerobic incubation at 37 degrees C for at least 18 h. 4. MIC reading confirmed by counting bacteria growing on specific solidified media. In this study the method for calculation of ADIm and MRL is given for flumequine as model drug. On the basis of MIC50 values for E. coli strains, a MRL for flumequine of 1.0 microgram/g meat or 0.25 microgram/ml milk was calculated. It is suggested that, depending on the antibacterial spectrum of the antibiotic involved, the ADIm can be determined with selected indicator bacteria, incubated under simulated gastrointestinal conditions. PMID- 7871700 TI - Substitution of dietary calcium chloride for calcium carbonate reduces urinary ph and urinary phosphorus excretion in adult cats. AB - In a 4x4-wk cross-over study, eight adult cats were given four moist diets containing identical amounts of calcium (13.9 mmol/MJ) but with different ratios of calcium carbonate to calcium chloride, the calcium salts providing half of the total dietary calcium. Increasing amounts of calcium chloride were substituted for equimolar amounts of calcium carbonate. Higher intakes of calcium chloride caused significantly lower pH values in postprandial and 24-h urine samples. The urinary excretion of ammonium and titratable acid rose with increasing calcium chloride intake. The urinary concentrations of calcium and magnesium were not affected by the type of calcium salt, but the urinary excretion and concentration of phosphorus were significantly depressed when the amount of calcium chloride in the diet was increased. The results are discussed in the context of dietary prevention of and therapy for struvite urolithiasis in cats. PMID- 7871701 TI - Field evaluation of the efficacy of the fenbendazole slow-release bolus in the control of gastrointestinal nematodes of first-season grazing cattle. AB - The ability of fenbendazole slow release bolus (Panacur SR Bolus, Hoechst) to control gastrointestinal parasitism in calves during their first grazing season at pasture was evaluated in two field trials. The infection level on both investigated farms was low and the control animals did not develop parasitic gastroenteritis. However, it was possible to demonstrate significant differences in the parasitological and biochemical parameters between the control and treated groups during the grazing season. Faecal egg counts and blood pepsinogen levels in the control cattle at both trials sites were significantly higher than those of the bolus-treated cattle. PMID- 7871702 TI - Feasibility of continuous recording of fetal heart rate in the near term bovine fetus by means of transabdominal Doppler. AB - A transabdominal Doppler technique for the recording of fetal heart rate (FHR) was investigated in the bovine fetus. During the last 2 weeks of gestation recordings were made once or twice per week in eight cows by placing a 1.5 MHz Doppler transducer on the right ventral abdominal wall. Continuous FHR recordings with a duration of more than 30 min were obtained in 29 of the 35 sessions. Major displacements of the fetus were the main cause of recording failure. The overall mean baseline FHR was 105 +/- 1.5 bpm with a range of 90 to 125 bpm. The mean bandwidth of the baseline FHR was 10.8 +/- 0.7 bpm with a range of < 5 to 20 bpm. Periods with different bandwidths alternated. The alternation of bovine FHR patterns pointed to the existence of different fetal behavioural states. The mean number of accelerations of FHR was 7.1 +/- 1.0 per hour. Many of the accelerations coincided with visible or perceptible fetal body movements. Decelerations of FHR occurred less frequently (range 0 to 4 per h). A period of tachycardia accompanied by an increased number of fetal movements occurred in 3 of the 29 FHR recordings. This non-invasive technique appears to be suitable to study FHR patterns during gestation and to investigate the presence and characteristics of behavioural states in the bovine fetus. It also provides the possibility to study effects on the fetus of drugs administered to the dam. PMID- 7871703 TI - Seven cases of heartworm disease (dirofilariosis) in dogs in The Netherlands. AB - We present here the clinical history, diagnosis, and treatment of seven dogs with dirofilariosis. All dogs were imported into the Netherlands after residing in an area in which dirofilariosis is endemic. In three of these dogs the infection was occult, for the serological test was positive but there was no microfilaraemia. Weight loss, coughing, dyspnoea, and decreased exercise tolerance were the most prominent clinical signs. Two of the dogs had the characteristic electrocardiographic and radiographic signs of enlargement of the right heart. Treatment with thiacetarsamide and ivermectin resulted in complete remission in six dogs. One dog died, presumably as a result of acute renal failure. In the past year (1992-1993) seven cases of canine dirofilariosis were diagnosed, nearly equal to the number in the preceding 10 years (n = 9). This most probably reflects the greater sensitivity of the serological diagnosis of dirofilariosis in comparison with identification of microfilariae in the circulation, but a real increase in the number of dogs with dirofilariosis as a result of growing international traffic of tourists accompanied by pets cannot be excluded. PMID- 7871704 TI - Animal spongiform encephalopathies--an update. Part 1. Scrapie and lesser known animal spongiform encephalopathies. AB - The present article (part I) reviews recent developments in animal spongiform encephalopathies (SEs), with the exception of bovine spongiform encephalopathy (BSE), which is dealt with in part II. The article focuses on scrapie and describes epidemiological aspects and the prospects for a preclinical diagnosis. Up to now, confirmatory diagnosis of scrapie depended on histological examination of the brain, collected during post-mortem examination from sheep with clinical signs of the disease. An altered protein, PrPSc, can be detected in the brain of diseased animals. The demonstration of the same protein in the spleen and in peripheral lymph nodes of infected animals seems to offer interesting possibilities of arriving at a method for a preclinical diagnosis, and thus a diagnosis in the live animal. Progress has also been made in our understanding of the relationship between the genetic constitution and susceptibility of the host. Susceptibility is expressed as the survival time of sheep inoculated with scrapie. This was thought to be determined by a single genetic locus designated the Sip gene (scrapie incubation period gene). Putative markers for the two alleles of the Sip gene, sA and pA, have been discovered, consisting of restriction fragment length polymorphisms (RFLPs). In field tests, however, the link between these markers and the length of incubation time was far from consistent. These RFLPs were found to be situated outside the prion-protein coding region of the ovine gene. In later studies, RFLPs were detected inside this region. These markers appear to be more informative, i.e. they correspond with a difference in the length of the scrapie incubation period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871705 TI - Animal spongiform encephalopathies--an update. Part II. Bovine spongiform encephalopathy (BSE). AB - An update on animal spongiform encephalopathies other than BSE was presented in part I of this article. Part II of this article focuses on bovine spongiform encephalopathy (BSE). The article describes clinical signs, histological and other changes leading to a diagnosis, the differential diagnosis, and the prospects for pre-clinical diagnosis of this disease. It describes the origin and course of the epidemic in the UK and discusses the question why it is only the UK which has witnessed such a large-scale epidemic. Predicted to arrive much earlier, the epidemic now finally seems to have passed its peak. The article goes on to discuss the chance of the disease occurring in a country like the Netherlands and the measures taken to prevent and control the disease, should it occur. The article concludes with a discussion of what has been found with regard to genetic factors, the results of experimental and unintentional artificial transmission of BSE to various species, and possible implications for human health. PMID- 7871706 TI - A study of the biomechanical properties of the adult equine linea alba: relationship of tissue bite size and suture material to breaking strength. AB - The purposes of this study were to mechanically determine the optimal tissue bite size and to evaluate seven suture materials at their largest commercially available size for breaking strength and stiffness using cadaveric adult equine linea alba. Soft tissues were removed from the abdominal fascia of 16 adult horses. Individual test sections were created from the entire linea alba and labeled (1 through 6) starting at the umbilicus and extending craniad. A single biomechanical test was performed on each test section. Tissue bite size (3, 6, 9, 12, 15, 18, and 21 mm) significantly altered breaking strength directly in a logarithmic fashion (P < .0001; R2 = 0.94). Tissue bite size accounted for 44% and linea alba thickness for 24% of the variability in breaking strength of the equine linea alba. The optimal tissue bite size for adult horse was 15 mm from the edge of the linea alba based on lack of significant gain in breaking strength. There were no differences in breaking strength among horses, horses weight, or left and right test sections. Test sections taken from near or at the umbilicus had greater breaking strength (P < .005) and thicker linea alba (P < .001) when compared with more cranial test sections. Linea alba thickness alone accounted for 34% of the variability in breaking strength associated with test section position. There were no differences in linea alba stiffness among tissue bite sizes. All suture loops failed before complete fascial disruption, and 52 of 56 (93%) suture loops failed at the knot.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871707 TI - Effects of 0.05% chlorhexidine lavage on the tarsocrural joints of horses. AB - In six horses, a 0.05% solution of chlorhexidine diacetate was used to lavage one tarsocrural joint; the contralateral control joint was lavaged with lactated Ringer's solution. Horses were evaluated daily for lameness. Synovial fluid samples were collected on days 1, 4, and 8 for determination of protein concentration, total and differential leukocyte counts, and mucin clot formation. After death on day 8, synovium and osteochondral samples were collected from the tarsocrural joints for examination of morphology and proteoglycan staining. Lavage with chlorhexidine solution caused lameness that was reduced but still evident at day 8. Synovial protein concentration was significantly increased by chlorhexidine lavage; the greatest increase occurred on day 1. Joint lavage increased synovial leukocyte counts on day 1, primarily by increasing polymorphonuclear (PMN) cell counts. Although total synovial leukocyte counts returned to normal by day 4, PMN cell counts remained elevated through day 8; PMN cell counts for chlorhexidine-lavaged joints were typically twice that of control joints. Chlorhexidine lavage caused synovial ulceration, inflammation, and abundant fibrin accumulation. Consistent differences in proteoglycan staining were not detected between control and chlorhexidine-lavaged joints. Joint lavage with 0.05% chlorhexidine diacetate, the lowest known bactericidal concentration, is not recommended for equine joints. PMID- 7871708 TI - Effects of three intramedullary pinning techniques on proximal pin location and articular damage in the canine tibia. AB - The effects of three different techniques of intramedullary (IM) pin placement on pin location and incidence of stifle joint injury were evaluated using 70 cadaver canine tibiae after mid-disphyseal osteotomy. In 50 tibiae, pins were placed retrograde in either a nondirected (group A) or a craniomedially directed fashion (group B) with 25 tibiae in each group. Pins were driven normograde (group N) in 20 tibiae. All the stifles were dissected to qualitatively evaluate pin interference with different joint structures. End-on radiographs of the tibial plateaus were used to quantitatively evaluate pin location. Interference with the caudal cruciate ligament, medial meniscus, lateral meniscus, or meniscal ligaments was not observed in any group. There was a significant association between pinning technique and incidence of involvement of the cranial cruciate ligament (P < .005), patella (P < .001), patellar ligament (P < .005), and femoral condyle (P < .01). Pin location for group A was significantly different from either other group in a cranial-caudal direction (P = .003), and was significantly different from group N in a medial-lateral direction (P = .005). No significant difference was observed between pin location for groups B and N in either plane. It was concluded that although nondirected retrograde pinning cannot be recommended, retrograde pins directed craniomedially may be an acceptable technique for the repair of proximal to mid-diaphyseal tibial fractures if care is taken to properly seat the pins. PMID- 7871709 TI - Evaluation of the lateral collateral ligament after fibular head transposition in dogs. AB - Cranial transposition of the fibular head stabilizes the stifle joint by displacing the distal attachment of the lateral collateral ligament (LCL). The forces applied to the LCL after displacement may cause ligamentous elongation. This investigation evaluated the morphological, histological, and biomechanical changes of the LCL after fibular head transposition (FHT) in dogs. Unilateral cranial cruciate ligament (CCL) excision and FHT were performed on 25 dogs. Cross sectional area, length, histological, and structural properties of the LCL were evaluated 3 weeks, 4 months, and 10 months after surgery. Ligament length means were significantly increased at week 3, month 4, and month 10 compared with intraoperative length means. No significant changes in elongation were observed after week 3. Fibrovascular proliferation within the LCL increased the cross sectional area and associated structural properties. PMID- 7871710 TI - Comparison of a biofragmentable intestinal anastomosis ring with appositional suturing for subtotal colectomy in normal cats. AB - A subtotal colectomy was performed on 12 normal adult cats using an interrupted apposing suture pattern of monofilament polyglyconate (n = 6) or a biofragmentable intestinal anastomosis ring (Valtrac, Davis and Geck Company, Danbury, CT) (n = 6) composed of polyglycolic acid and barium sulfate. Abdominal radiographs were made daily, beginning 10 days after surgery, to determine fragmentation rates of the anastomosis ring. The cats were euthanatized 30 days after surgery, and a gross and histopathological evaluation of anastomotic healing and stricture formation was performed. The technique for implantation of the anastomosis ring was easy to learn and required only two purse string sutures to complete. Intraoperative complications associated with the anastomosis ring were minor, and included problems with purse string suture placement, small serosal tears, and spasms of the colon that reduced the lumenal diameter. There were no intraoperative complications in the cats with sutured anastomoses. Postoperative recovery was uneventful in all cats. The anastomosis rings fragmented 12.2 +/- 1.1 days (mean +/- standard deviation [SD]) after implantation and passed in the stool 3.8 +/- 1.9 days later without clinical signs in five of six cats. There were no statistically significant differences between the time required to perform the anastomosis (P = .348), postmortem gross anastomosis grades (P = .088), or percent of lumenal stricture (P = .178) between the two groups. Histologically, the only significant differences were an increased muscular inversion in the anastomoses performed using the fragmentable ring (P = .039) and an increased muscular eversion in the sutured anastomoses (P < .001) compared with normal colonic architecture. PMID- 7871711 TI - Incomplete ossification of the humeral condyle in spaniels. AB - An evaluation of 157 dogs with humeral fractures was performed. Cocker spaniels were more likely to have humeral condylar fractures (HCFs) than other breeds (P < .001). Male cocker spaniels were at increased risk (P < .001). Cocker spaniels had more bilateral HCFs than other breeds of dogs (P < .001). Eighteen dogs (17 purebred spaniels and 1 crossbred spaniel) with HCFs of unknown cause or occurring with normal activity were further studied, using radiography of their humeral condyle bilaterally (n = 18), computed tomography (n = 3), biopsy (n = 2), bone scintigraphy (n = 2), and genetic evaluation (n = 8). Fourteen of these 18 dogs had a nonfractured contralateral condyle. Twelve (86%) of the 14 nonfractured humeral condyles had a radiolucent line within the center of the condyle, 13 (93%) had radiographic signs of degenerative joint disease and an abnormal medial coronoid process, and six (43%) had periosteal proliferation involving the lateral epicondyle. Examination of biopsy samples from the fracture sites of two cocker spaniels showed fibrous tissue present at the fracture surfaces. The results of this study suggest an association between incomplete ossification of the humeral condyle in cocker spaniels and Brittany spaniels and a high prevalence of HCFs. Eight affected cocker spaniels with available pedigree information were found to be genetically related, suggesting that incomplete ossification of the humeral condyle may be a genetic disease with a recessive mode of inheritance. PMID- 7871712 TI - Holding power of threaded external skeletal fixation pins in the near and far cortices of cadaveric canine tibiae. AB - We compared the pin-bone interfaces at the near and far cortical penetration sites of positive-profile end-threaded external fixation pins in cadaveric canine tibiae. The holding power of the pins in each cortical surface was independently measured in 21 pin-bone sections. Scanning electron microscopy (SEM) was used to compare subjectively the microstructural appearance of the pin-bone interfaces at the near and far cortical penetration sites in eight pin-bone sections. The far cortical penetration site provided greater holding power than did the near cortical site. SEM evaluation suggested more bony microfractures and debris with less pin-bone SEM evaluation suggested more bony microfractures and debris with less pin-bone interlock in the near cortical penetration sites than in the corresponding far cortical penetration sites. This study showed that after low speed power insertion of positive-profile end-threaded pins in canine cadaveric tibiae, the near cortical penetration site contributes approximately 25% less to the overall holding power of the pin than does the far cortical penetration site. PMID- 7871713 TI - The effect of occlusive and semi-occlusive dressings on the healing of acute full thickness skin wounds on the forelimbs of dogs. AB - This project compared the effects of hydrocolloid (HC) and hydrogel (HG) occlusive dressings and a polyethylene (PE) semi-occlusive dressing on the healing of acute full-thickness skin wounds on the forelimbs of 10 dogs. All treatments resulted in a similar degree of healing at postoperative days 4 and 7. No significant differences existed in the number of wounds that were more than 90% healed at postoperative day 28 between the group treated with the HG dressing and the group treated with the PE dressing. There were significantly fewer wounds more than 90% healed at postoperative day 28 in the group treated with the HC dressing. Wounds under the HG dressing had the largest mean percentage of contraction at postoperative days 21 and 28. Wounds under the HG dressing also had the largest contraction/re-epithelialization ratio (postoperative days 21 and 28) compared with wounds under the PE and HC dressings. Wounds under the PE dressing had a significantly higher mean percentage of re-epithelialization than wounds under both occlusive dressings on postoperative days 14, 21, and 28. Wounds under the two occlusive dressings had exuberant granulation tissue present more often than wounds under the PE dressing. The two occlusive dressings had significantly higher bacterial counts on wounds compared with wounds under the PE dressing; analysis of variance (ANOVA), P = .0008. Wounds under the HC dressing showed the poorest healing in all parameters. PMID- 7871714 TI - Femoral strain distribution and subsidence after physiological loading of a cementless canine femoral prosthesis: the effects of implant orientation, canal fill, and implant fit. AB - Twelve normal greyhound femora were divided into three groups. In group one, femoral stems were placed in neutral position with maximal fill. Group two had undersized femoral stems placed in neutral position. Group three had undersized femoral stems placed in varus position. Intact and implanted femora were loaded from 10 newtons (N) to 300 N in axial compression at a rate of 25 N/s for 10 replications. A strain gauge analysis showed that the strain distribution of all implanted femora were substantially different from intact femora, but femora with large implants placed in neutral position had the least amount of deviation from normal. An undersized stem in neutral position had significantly less compressive longitudinal strains along the proximomedial and proximocranial cortices. An undersized stem in varus position improved implant fit along the proximomedial and distolateral cortices, which resulted in increased tensile hoop strains. There were multiple significant correlations between the strain data and implantation variables (implant alignment, canal fill, and implant fit). Subsidence was significantly greater for the undersized implant in neutral position. There was not a difference in subsidence between the large neutral and varus groups. The most important variable that decreased subsidence was increased lateral implant fit (r = -0.86, P = .0003). PMID- 7871715 TI - The anatomic basis of a free vascularized bone graft based on the canine distal ulna. AB - The anatomy of the canine distal ulna was evaluated to determine its potential as a free vascularized bone graft. Twelve cadavers were studied by gross dissection and nonselective and selective angiography. The caudal interosseous artery consistently served as a source artery to the distal ulnar periosteal vasculature in all dogs. The diameters of the caudal interosseous artery and venae comitantes were large enough to permit microvascular anastomoses. Nonselective perfusions of the brachial artery demonstrated large barium-filled vessels within soft tissues surrounding the ulna with anastomotic connections between medullary and periosteal vasculature. Grafts selectively perfused through the caudal interosseous artery (periosteal circulation only) had barium-filled vessels within the muscular cuff, periosteum, cortical bone, and medullary canal of the ulna. A surgical approach to remove the distal ulna along with an intact musculoperiosteal cuff and its associated vasculature is described. PMID- 7871716 TI - Unintentional duplicate reporting of equine enterocutaneous fistulae. PMID- 7871717 TI - Proteolysis of p6.9 induced by cytochalasin D in Autographa californica M nuclear polyhedrosis virus-infected cells. AB - Cytochalasin D, a fungus-derived compound that interferes with actin polymerization, inhibits Autographa californica M nuclear polyhedrosis virus production in infected Spodoptera frugiperda (IPLB-Sf-21) cells. Cytochalasin D appears to inhibit nucleocapsid morphogenesis by interfering with nucleoprotein packaging. We were interested in determining, therefore, whether the drug affected the synthesis or processing of p6.9, the major core protein involved in nucleoprotein packaging. We found that cytochalasin D had no effect on the synthesis, phosphorylation, or dephosphorylation of p6.9, but that it induced the proteolysis of p6.9, an effect which could account for the inhibition of nucleocapsid morphogenesis. We also determined that the cytochalasin D-induced proteolysis of p6.9 was reversible upon removal of the drug, even in the absence of protein synthesis. PMID- 7871718 TI - Positive and negative regulation at the herpes simplex virus ICP4 and ICP0 TAATGARAT motifs. AB - The control of the ICP0 and ICP4 immediate early genes of herpes simplex virus (HSV) can critically determine the course of viral lytic or latent infections. Their promoters contain so-called TAATGARAT motifs that are activated via a multiprotein complex which includes cellular proteins Oct-1 and HCF and the viral activator (VP16 (= Vmw65, alpha TIF). Relative to the ICP4 promoter TAATGAGAT sequence, the ICP0 promoter motif has a 5' extension that includes a full octamer sequence (ATGCTAATGATAT). It seemed possible that this overlapping octamer site might render the ICP0 promoter element more active by allowing tighter binding of the Oct-1/VP16 complex or more vulnerable to repression by other Oct proteins. Our experiments favor the former possibility. On the one hand, the extended ICP0 site shows stronger binding of the Oct-1/VP16 complex compared to the ICP4 site. Moreover, transcription of a reporter gene with multiple ICP0 sites is strongly activated by VP16 in transfected cells. On the other hand, the ICP0 site is largely refractory toward repression by a different Oct factor (N-Oct2 = Brn1) which competes with Oct-1/VP16 for the site. In marked contrast, multiple copies of the conventional TAATGAGAT motif of ICP4 are poorly activated by VP16, and transcription from this site can be completely repressed by N-Oct2. However, inclusion of the neighboring CGGAAR motifs from the ICP4 promoter, which bind factors GABP alpha and beta, results in a strong synergistic activation. This activity, like that of the complete ICP4 promoter, becomes refractory to repression by competing N-Oct2. Thus the standard TAATGARAT motif of ICP4 is by itself less active and more vulnerable to repression than the extended ICP0 motif, and its activation depends upon synergism with neighboring DNA sites and their cognate factors. This difference between the two types of TAATGARAT motifs may allow for a more complex transcriptional regulation by factor combinations. PMID- 7871719 TI - Restriction of avian reovirus in primary chicken embryo tendon cells. AB - Upon infection of the gastrointestinal tract, some avian reovirus strains spread to multiple organs of their natural hosts, chickens, and establish persistent infections. One manifestation of chronic infection is the development of arthritis in the tendons of the chickens. In order to study events associated with persistent infections in the tendon, primary cultures of chick embryo tendon (CET) cells were infected with avian reovirus. The CET cells supported a noncytopathic infection for at least 16 days, shedding lower amounts of progeny virus than a permissive cell culture, chick embryo fibroblasts (CEF). The virus from the CET cells was predominantly cell-associated unlike virus from the CEF cells. Initiation of infection was much slower in CET cells as indicated by fewer cells expressing antigen or exporting virus over the first 48 hr. However, most CET cells gained these abilities over the course of infection. Initial events in virus infection, binding, and penetration were not impaired in tendon cells but transcription of single-strand RNA was delayed and double-strand RNA production was clearly inhibited. The CET cells supported efficient replication of another avian virus, Newcastle disease virus, suggesting that restriction for avian reovirus is virus specific, in addition to being tissue specific. PMID- 7871720 TI - Measles virus persistence in an immortalized murine macrophage cell line. AB - Persistent infection with the Edmonston strain of measles virus (MV) has been established in IC-21 cells, an immortalized murine macrophage cell line. Persistence was established immediately without syncytia formation or cytopathic effects. MV was expressed in the majority of the cells as evidenced by immunofluorescence microscopy, flow cytometry, infectious centers assays, and limiting dilution analysis. Hemagglutinin (H) and phosphoprotein expressed in persistently infected IC-21 cells had retarded migration in SDS-PAGE gels when compared to these proteins expressed in Vero cells. H protein differences were also found between freshly infected IC-21 cells and persistently infected IC-21 cells passaged for over 2 years. Six sublines of IC-21 cells, infected at different times, have maintained these characteristics for 2 years of passage. During this time period the intensity of immunofluorescence and the number of infectious virus particles recoverable fluctuated in five of the six cell lines. In one cell line virus expression remained at a consistent high level. The ability to establish a persistent MV infection in murine macrophages allows studies using a cell important in disseminating the infection. It facilitates experiments on immunological aspects of viral immunity by enabling cell mixing experiments with histocompatible cell populations and by making available the wide array of cellular and humoral reagents in the mouse. PMID- 7871721 TI - Autocatalytic processing of the 223-kDa protein of blueberry scorch carlavirus by a papain-like proteinase. AB - The first open reading frame of the blueberry scorch carlavirus (BBScV) genome encodes a putative replication-associated protein of 223 kDa (p223). A pulse chase analysis of viral RNA translated in vitro in rabbit reticulocyte lysate revealed that p223 was proteolytically processed. Using a full-length ORF 1 cDNA clone in a coupled in vitro transcription/translation reaction, we confirmed that the ORF 1 gene product of BBScV processes autocatalytically. From sequence alignments with phylogenetically related viruses, including tymoviruses, we predicted that p223 contained a papain-like proteinase domain with a putative catalytic cysteine994 and histidine1075. A second possible proteinase domain, which contained cysteine895 and histidine984 residues with similar spacing but was otherwise less similar to the viral papain-like proteinases, was identified immediately upstream of the predicted catalytic site. The cleavage site of the proteinase was predicted to be between the putative helicase and the polymerase domains, possibly between or close to glycine1472 and alanine1473. Supporting these predictions, deletion of the 2091 nucleotides encoding the C-terminal region of p223, which contained the putative RNA polymerase domain and the putative cleavage site of the polyprotein, abolished autoproteolysis. Deletion of the 2061 nucleotides encoding the N-terminal region, which contained the putative methyltransferase domain, did not affect autoproteolysis. Alteration of cysteine994, histidine1075, or glycine1472 abolished autoproteolysis in vitro, supporting the involvement of these residues at the catalytic site and cleavage site. Alteration of the upstream cysteine895 and histidine984 residues did not affect processing in vitro. Capped BBScV full-length transcripts containing mutations in the codons for either cysteine994 or histidine1075 were not infectious in the systemic host plants Chenopodium quinoa and C. amaranticolor, whereas alteration of glycine1472 signficantly decreased but did not abolish infectivity. Transcripts containing mutations in the codons for either cysteine895 or histidine984 also were infectious, but resulted in delayed symptom expression in plants. PMID- 7871722 TI - Postattachment neutralization of papillomaviruses by monoclonal and polyclonal antibodies. AB - Postattachment neutralization of papillomaviruses (PVs) was analyzed in three PV infectivity models: (i) the BPV-1-induced focus-forming assay using C127 cells; (ii) in vitro abortive infection of rabbit RK-13 and Sf1Ep cells with CRPV; and (iii) HPV-11-induced morphological transformation of human foreskin chips in the athymic mouse xenograft system. In each assay system, aliquots of infectious virus were added to the appropriate target cells and incubated at 37 degrees, followed at various postinfection time intervals with neutralizing monoclonal antibodies (N-MAbs) that target surface conformational epitopes. In all three model systems, the N-MAbs were able to neutralize PV infection when added as late as 8 hr after addition of infectious PV to host cells. These results imply that papillomaviruses attach to but do not penetrate inside host cells for a significant period of time and that the bound virus is thus still susceptible to neutralization by neutralizing antibodies. PMID- 7871723 TI - Analyses of homologous rotavirus infection in the mouse model. AB - The group A rotaviruses are significant human and veterinary pathogens in terms of morbidity, mortality, and economic loss. Despite its importance, an effective vaccine remains elusive due at least in part to our incomplete understanding of rotavirus immunity and protection. Both large and small animal model systems have been established to address these issues. One significant drawback of these models is the lack of well-characterized wild-type homologous viruses and their cell culture-adapted variants. We have characterized four strains of murine rotaviruses, EC, EHP, EL, and EW, in the infant and adult mouse model using wild type isolates and cell culture-adapted variants of each strain. Wild-type murine rotaviruses appear to be equally infectious in infant and adult mice in terms of the intensity and duration of virus shedding following primary infection. Spread of infection to naive cagemates is seen in both age groups. Clearance of shedding following primary infection appears to correlate with the development of virus specific intestinal IgA. Protective immunity is developed in both infant and adult mice following oral infection as demonstrated by a lack of shedding after subsequent wild-type virus challenge. Cell culture-adapted murine rotaviruses appear to be highly attenuated when administered to naive animals and do not spread efficiently to nonimmune cagemates. The availability of these wild-type and cell culture-adapted virus preparations should allow a more systematic evaluation of rotavirus infection and immunity. Furthermore, future vaccine strategies can be evaluated in the mouse model using several fully virulent homologous viruses for challenge. PMID- 7871724 TI - Configuration and terminal sequences of the simian varicella virus genome. AB - The simian varicella virus (SVV) genome is a linear DNA molecule consisting of a unique short (Us) and a unique long (UL) region. The Us is bounded by internal (IR) and terminal inverted repeats and inverts such that virion DNA contains equimolar amounts of two genome isomers. We have sequenced the right and leftward termini and the UL-IR junction region of the SVV genome. A sequence motif common to other herpesviruses, consisting of A and T residues surrounded by G+C-rich regions, was found near the rightward terminus of the SVV genome. Sequence analysis showed no repeats surrounding the UL region of the genome. Nucleic acid hybridization and polymerase chain reaction (PCR) amplification using primers from the right and leftward ends of the SVV genome indicated that the UL region inverts. PCR amplification also showed that, compared with virion DNA, SVV genomes with connected termini are increased in infected cell DNA, suggesting the presence of circular or concatemeric genomic molecules. PMID- 7871725 TI - Protection of coliphage lambda O initiator protein from proteolysis in the assembly of the replication complex in vivo. AB - We have shown previously that, in contrast to the free coliphage lambda O initiator protein rapidly degraded by ClpP/ClpX protease, the lambda present in the replication complex (RC) is protected from proteolysis. Now we asked at which step of the pathway of RC assembly in vivo does the stabilization of lambda O occur. In accordance with the in vitro established order we found that lambda P and DnaB helicase functions are, but those of DnaJ and GrpE chaperones are not, required for the protection of lambda O from proteolysis. Therefore, our results suggest that the first lambda O protecting structure of the pathway of RC assembly is the lambda O-lambda P-DnaB preprimosome. The next step of the pathway, the chaperone-mediated rearrangement of the preprimosome, is not essential for lambda O stabilization. However, in contrast to other chaperones, the DnaK function was required for the protection of lambda O from proteolysis, suggesting an earlier access of DnaK to the pathway of RC assembly in vivo, in accordance with current models by which molecular chaperones facilitate protein assembly. PMID- 7871726 TI - The Gag-Pol encoded proteinase of an avian retrovirus expressed in E. coli can produce a novel proteinase (PR + IleGly) that is two amino acids larger at its carboxy-terminal region than the major Gag proteinase (PR). AB - Gag-Pol frameshift translational products of avian retroviruses (e.g., myeloblastosis associated virus, MAV) contain a putative proteinase species of 131 amino acids that maps between the NC/PR and the PR/RT processing sites. Expression in Escherichia coli of an in-frame PR precursor that contains the natural NC/PR processing site and is translationally terminated at the PR/RT site leads to formation of a Gag-Pol proteinase of the expected molecular size (131 amino acids) and a novel PR product of 126 amino acids. This product extends 2 amino acids downstream of the gag-encoded 124 amino acids, and its proteolytic cleavage is promoted by conditions favorable for enzyme catalysis, is blocked by a specific MAV proteinase inhibitor, and can be demonstrated also for corresponding peptide substrates. The new self-processing cleavage product is termed PR(+IleGly) and exhibits similar, but slower, catalytic parameters than those of the Gag PR. PMID- 7871727 TI - Both bipartite geminivirus movement proteins define viral host range, but only BL1 determines viral pathogenicity. AB - Bipartite geminiviruses such as squash leaf curl virus (SqLCV) encode two movement proteins (MPs), BR1 and BL1, that are essential for virus movement and systemic infection of host plants. BR1 has been implicated in the host range properties of the virus, and BL1 in viral pathogenic properties. To more precisely examine the roles of each MP, we have introduced missense and deletion mutations into the coding sequence of both BR1 and BL1, and examined the effects of these mutations on viral infectivity and the production of disease symptoms in pumpkin, squash, and Nicotiana benthamiana. For each MP, a range of mutant phenotypes from partially to fully defective was observed that affected the overall level and rate of infectivity. However, only mutations in BL1, and not BR1, affected the severity of disease symptoms, confirming our earlier finding that BL1 is responsible for the production of disease symptoms. For all mutants, the cucurbit hosts were found to be more permissive for viral movement than was N. benthamiana, and several mutations in both BL1 and BR1 produced host-specific phenotypes, retaining high levels of infectivity in pumpkin and squash, but abolishing infectivity for N. benthamiana. Unexpectedly, functional SqLCV coat protein (AR1) was found to specifically mask the phenotypes of certain BR1 mutations, suggesting some redundancy of function between coat protein and the BR1 MP and an interaction of AR1 with the viral movement pathway. AR1 and BR1 have similar nucleic acid binding affinities, suggesting a possible mechanism for the observed effects of the viral coat protein on viral movement. PMID- 7871728 TI - Gene organization in herpesvirus of turkeys: identification of a novel open reading frame in the long unique region and a truncated homologue of pp38 in the internal repeat. AB - The DNA sequence of a 4.792-kb fragment comprising 3.176 kb of the long unique region (UL) and 1.605 kb of the internal repeat (IRL) flanking UL of herpesvirus of turkeys (HVT) was determined. Three potential open reading frames (ORFs) and an origin of replication have been identified. ORF 1, which maps entirely within UL, has the capacity to code for an 82K protein, 731 amino acids long, which has a counterpart in Marek's disease virus (MDV) but not in other herpesviruses. ORF 2 has the potential to encode a protein consisting of 129 amino acids with a predicted M(r) of 13.5K which appears to be unique to HVT. ORF 3 is encoded entirely within IRL and codes for an 84 amino acids long protein with a predicted M(r) of 8.5K. ORF 3 shows significant homology with the C-terminal region of the MDV-1-specific phosphoprotein pp38 and its recently identified homologue in MDV 2. Northern blot analysis of RNA extracted from HVT-infected chick embryo fibroblasts identified a 5.6-kb RNA transcribed in a leftward direction toward UL scanning ORF 1, ORF 2, and ORF 3 and a 2.8-kb also transcribed leftward toward UL which spanned only ORFs 2 and 3. In addition, a 2.3- to 2.8-kb RNA family was transcribed rightwards through the origin of replication. In vitro transcription and translation of ORF 1 and ORF 3 resulted in the synthesis of polypeptides consistent with their expected M(r), but ORF 2 failed to produce any translation product. PMID- 7871729 TI - A comparative study of higher primate foamy viruses, including a new virus from a gorilla. AB - Few foamy (spuma) retroviruses have been investigated in molecular detail, despite their previous isolation from several mamalian species, including ten neutralization serotypes from various primates. Here, we have studied a new gorilla foamy virus (SFV-Gg) and investigated its functional and phylogenetic relationship to the human (HFV) and other primate foamy viruses, including that recently described in orangutans (SFV-11). Nucleotide sequencing of PCR products obtained from the R/U5 region of the LTR, gag, and pol genes revealed a close relationship between HFV and three chimpanzee isolates (SFV-6, SFV-7, and SFV cpz). The SFV-Gg, SFV-11, rhesus macaque (SFV-1), and African green monkey (SFV 3) isolates were more divergent. To explore functional relationships, primate foamy virus transactivation of HFV LTR driven beta-galactosidase expression in a newly constructed cell line, BHLL, was investigated. HFV, SFV-6, and SFV-7 potently transactivated HFV LTR driven lacZ gene expression, SFV-Gg induced expression approximately 10-fold less efficiently, and SFV types 1, 2, 3, and 11 did not significantly transactivate the HFV LTR. It was, thus, possible to assay serum neutralizing activity in SFV-infected primates against HFV, SFV-6, and SFV 7 by reduction of beta-galactosidase activity following infection of the indicator cell line. Sera from infected chimpanzees and gorillas neutralized, to varying degrees, each of these three viruses, whereas orangutan sera did not. Our results, based on DNA sequences and functional assays, support the conclusion that HFV is closely related to foamy viruses of chimpanzee origin. PMID- 7871730 TI - Analysis of the role of the amino-terminal peptide of vaccinia virus structural protein precursors during proteolytic processing. AB - Several VV structural proteins are produced by the removal of amino-terminal peptides from their cognate precursors. In the experiments reported here, directed genetic approaches were used to investigate the possible role of these terminal peptides in protein processing. As a model system, the FLAG epitope tagged P25K precursor was used to prepare constructs in which the 31-amino-acid P25K N-terminal peptide was removed or replaced by heterologous sequences, while the -A-G*-A- cleavage motif was retained. Only a trace amount of the leaderless P25KF(delta 31) polypeptide was found within the mature virions, implying that proteolytic processing is necessary for the incorporation of the 25K product into mature virions. In trans-processing assays, significant levels of the 25K product were generated from wild-type P25KF and P4b:25KF, which consists of the 61-amino acid P4b terminal peptide, and from P4b:25KF with 15, 30, or 44 residues of the amino terminus deleted. In contrast, only a small amount of 25K was produced from the TK:25KF, which contains the amino-terminal 30 residues of VV thymidine kinase, a protein which is not cleaved under normal circumstances. Furthermore, it has been hypothesized that a hydrophobic residue is required at position P4 relative to the -A-G*-A- motif for the cleavage to take place. An intermediate level of the 25K product was detected from the TK:25KF(Q29V) mutant which has the glutamine residue at P4 replaced with a valine residue, suggesting that the hydrophobic P4 residue and additional substrate determinants in the N-terminal peptide region are required for the proteolytic processing reaction to occur normally. Taken together, these data suggest that the amino-terminal peptides of the VV core proteins are to some extent interchangeable and that the residues proximal to the AGA site are of most importance. PMID- 7871732 TI - A single nucleotide change in the coat protein gene of tobacco mosaic virus is involved in the induction of severe chlorosis. AB - YSI/1 is a mutant of the common strain (U1) of tobacco mosaic virus (TMV) which induces a severe yellow mosaic in Nicotiana tabacum instead of the light green/dark green mosaic induced by its parental U1 virus. Although there was less coat protein (CP) in whole leaf extracts of YSI/1-infected leaves than in U1 infected leaves, severalfold more CP was found in the chloroplasts, most of which was associated with the thylakoids. Sequencing the CP genes of both viruses showed the presence of nucleotide differences at viral RNA positions 5770 and 6127, both of which result in amino acid replacements; YSI/1 has an Asp-->Val change at amino acid 19 and a Ser-->Phe change at amino acid 138. A common strain TMV engineered to contain the YSI/1 3' end sequences, including the CP, induced the severe yellow mosaic of the YSI/1 mutant. A chimeric virus with the change only at nucleotide 5770 (amino acid 19) in the CP induced a severe yellow mosaic, showing that this replacement is involved in the induction of chlorosis by YSI/1. A second isolate of the same chimera also induced severe yellow mosaic symptoms; sequencing showed that it had gained the change at nucleotide 6127. However, a chimeric virus with the change only at nucleotide 6127 (amino acid 138) in the CP was unable to induce the severe yellow mosaic. PMID- 7871731 TI - Transcription regulation in Bacillus subtilis phage phi 29: expression of the viral promoters throughout the infection cycle. AB - Transcription of the genome of Bacillus subtilis phage phi 29 is tightly controlled, taking place in two stages, early and late. We have analyzed the abundance of the transcripts produced from each viral promoter throughout the infection cycle. We compare the relative strength of each promoter, as well as get a better understanding of the regulatory events, finding a new promoter regulated by the viral protein p4. The two strong early promoters, A2b and A2c, responsible for the expression of genes 6 to 1, are coordinately repressed by the viral protein p4, although repression is not complete: both promoters are still active at late times of infection. Since repression by protein p4 was very efficient in vitro, and affects its own synthesis, it is likely that this protein is produced in limiting amounts, not being bound to all viral DNA molecules present in the cell at a given time. Protein p4, also known to activate the late promoter responsible for the expression of all the structural and morphogenetic genes, is the key regulator of phage phi 29 development. PMID- 7871733 TI - Nucleotide sequences of the genes encoding the putative attachment glycoprotein (G) of mouse and tissue culture-passaged strains of pneumonia virus of mice. AB - The sequences of the genes encoding the putative attachment (G) proteins of pathogenic (strain J3666) mouse lung-passaged and nonpathogenic (strain 15) tissue culture-passaged strains of pneumonia virus of mice (PVM) have been determined. In both cases the major polypeptide was synthesised from the second open reading frame (ORF), a feature also found in the G gene of respiratory syncytial (RS) virus, another pneumovirus. However, the ORFs of the G genes of the two PVM strains were initiated at different nucleotide positions in the mRNA and comparison of hydrophobicity profiles revealed the presence of the putative amino-terminal cytoplasmic domain in the strain J3666 G protein and its absence in the predicted G protein of PVM strain 15. In common with the G protein of RS virus, the gene product of both PVM strains contained a high serine, threonine, and proline content. Indirect immunofluorescence analysis of BSC-1 cells expressing the G gene products confirmed the surface location of the proteins. Thus, the absence of a cytoplasmic domain does not interfere with the translocation of the G protein of PVM strain 15. In vitro translation of mRNA from the two PVM genes directed the synthesis of a larger polypeptide with the G gene of PVM strain J3666 than was seen with strain 15 G gene. In addition, a second protein was seen with strain J3666 mRNA which was the same size as the strain 15 G protein. PMID- 7871734 TI - Inhibition of cellular and SV40 DNA replication by the adeno-associated virus Rep proteins. AB - In order to define the mechanism used by the adeno-associated virus replication (rep) gene to mediate inhibition of cell proliferation, we have studied its effects on SV40 and cellular DNA replication. SV40 DNA replication was inhibited by the presence of the rep gene in human 293 cells, and the inhibition was not linked to suppression of SV40 early gene expression. Using double immunofluorescence assays that measured both rep gene expression and bromodeoxyuridine incorporation, we found that the presence of the Rep78 and Rep68 proteins correlated with inhibition of cellular DNA synthesis in NIH3T3 cells. This links the rep gene's anti-proliferative effects to either: (i) a direct inhibition of DNA synthesis or (ii) a possible cell cycle block. PMID- 7871735 TI - SV40 VP1 assembles into disulfide-linked postpentameric complexes in cell-free lysates. AB - The simian virus 40 (SV40) capsid is composed of pentameric capsomeres of the major structural protein, Vp1. The chemical nature of Vp1-Vp1 interactions, as well as the role of the minor structural proteins, Vp2 and Vp3, in SV40 assembly is not clear. We show here that Vp1 molecules synthesized in rabbit reticulocyte lysates self-assembled into postpentameric 12S complexes in the absence of other viral structural proteins and in a time and concentration dependent manner. The 12S complexes were resistant to perturbants of noncovalent interactions but were sensitive to reduction by dithiothretiol. Nonreducing SDS-PAGE analysis revealed disulfide-linked VP1 complexes of > 400 kDa. Our results are consistent with crystallography studies of SV40 which suggest involvement of disulfide bonds at a postcapsomeric stage of viral assembly. PMID- 7871736 TI - The quaternary structure of the adenovirus 12 early region 1B 54K protein. AB - The quaternary structure of the adenovirus early region 1B 54K protein has been examined under denaturing and nondenaturing conditions. In the presence of SDS the protein has a strong tendency to form disulfide-linked high-molecular-weight polymers. Under nondenaturing, but reducing, conditions the in vitro-translated 54K polypeptide forms oligomers (probably tetramers) of molecular weight approximately 2 x 10(5). After subcellular fractionation of Ad12 early region 1 transformed cells, the 54K E1B protein present in the cytoplasm had a molecular weight similar to that determined for the in vitro-translated material. However, two populations of the viral protein could be distinguished in the nucleus-one of a size similar to that seen in the cytoplasm and the other of appreciably higher molecular weight (approximately 2 x 10(6)). No difference in migration pattern was observed after treatment of the nuclear extract with DNase I or RNase. A proportion of the Ad12 E1B 54K protein in both the high- and the low-molecular weight populations in the nucleus was found to form a complex with p53, and it is therefore concluded that the very high molecular weight derives from interaction with an, as yet, unidentified component. PMID- 7871737 TI - The expression levels of the human papillomavirus type 16 E7 correlate with its transforming potential. AB - The transforming potential of the human papillomavirus (HPV) type 16 has been defined largely in the E7, E6, and E5 oncoproteins, with the major transforming capability residing in the E7 gene. In this paper, we found that in cooperation with the activated ras, the HPV16 E7 gene when expressed in a retroviral vector could fully transform baby rat kidney (BRK) cells in transfections, whereas the same construct could only immortalize the BRK cells following retroviral infection. This inability to transform correlated with the low levels of E7 gene RNA expression in the viral infected cells, which harbor a lower number of copies of the E7 gene constructs. Cotransfection of the expression vector FV2E7, which gives high levels of E7 gene expression, and activated ras lead to rapid and efficient morphological transformation of BRK cells which grew easily in soft agar and induced large tumors in athymic nude mice. In contrast, cotransfections of the expression vector FV1E7, which gives lower levels of E7 gene expression, produced much lower numbers of transformed colonies which took longer to form, showed a retarded growth on soft agar, and induced smaller tumors in nude mice. Under these conditions, colonies of immortalized, but morphologically untransformed cells formed in large numbers. These results indicate that the transforming potential is directly correlated to the expression levels of the oncoprotein and that a threshold level of the E7 oncoprotein may be required before the cells can be fully transformed. This supports the hypothesis that the transformation processes include at least two separate and continuous steps which first lead to immortalization and then to metastasis, in agreement with the clinical progression of genital tumors from benign to malignancy. Such a progression may involve enhanced expression of the oncoproteins. PMID- 7871738 TI - Defective retroviral endogenous RNA is efficiently transmitted by infectious particles produced on an avian retroviral vector packaging cell line. AB - This report describes the contamination of "helper-free" stocks of defective retroviral vector with particles bearing retroviral endogenous RNA. An avian leukosis virus-based packaging cell line was developed from LMH cells that bear the ev1, ev3, and ev6 retroviral endogenous loci. The results show that an endogenous retroviral transcript (ev3) was packaged into virions produced by this packaging cell line and was efficiently transferred along with the vector to target cells. The titer of the ev contaminant particles was estimated at 50-100 CA-p27gag-expressing units/ml of supernatant. PMID- 7871739 TI - Characterization and biological activity of DI RNA dimers formed during cucumber necrosis virus coinfections. AB - Coinfections of synthetic transcripts from a cDNA clone of cucumber necrosis virus (CNV) and cDNA clones of defective interfering (DI) RNAs were previously demonstrated to contain DI-like RNAs approximately twice the size of the DI RNA used for co-inoculation. Analysis of these RNAs revealed that they are head-to tail repeats of CNV DI RNA sequence (dimers). Sequence analysis of 21 cloned dimer junctions indicated that approximately half of the junction sequences correspond to precise fusions of monomer units. A cDNA clone corresponding to a dimer of DI RNA 42 was constructed. Synthetic DI RNA 42 dimer transcripts were biologically active in coinfections, resulting in the accumulation of high levels of DI RNA 42 monomers. The possibility that dimers serve as templates for the generation of DI RNA monomers is discussed. PMID- 7871740 TI - Distinctive kinetics of the antibody-forming cell response to Sendai virus infection of mice in different anatomical compartments. AB - The single-cell ELISPOT assay was used to determine the frequency and isotype commitment of virus-specific antibody-forming cells (AFC) at different anatomical locations following intranasal Sendai virus infection of C57BL/6 and 129/Sv mice. AFC responses in the mediastinal and cervical lymph nodes showed sharp increases and declines, first of IgM AFC, peaking about 7 days after infection, and then of IgG and IgA AFC, peaking about 10 days after infection. A wave of IgM AFC preceding the other isotypes was less evident in the spleen, where peak frequencies of AFC occurred 14 days after infection. Virus-specific AFC appeared in the bone marrow with a unique kinetic pattern, increasing in frequency gradually over the first 3 weeks after infection to a plateau that remained constant. Circulating IgM and IgG achieved significant titers approximately a week after infection; IgM titers were transient, but IgG levels increased sharply and remained high, reflecting the longevity of the bone marrow AFC response. Strain differences in isotype bias were noted, particularly preferential switching to the gamma 2a gene in 129/Sv mice. The B-cell response to acute respiratory viral infection thus exhibits features that are distinct from the primary response to nonreplicating antigens. PMID- 7871741 TI - Characterization of infectious type D retrovirus from baboons. AB - Infectious virus resembling type D simian retrovirus (SRV) was isolated from Ethiopian baboons (Papio cynocephalus) (SRV-Pc) housed at the University of Washington Regional Primate Research Center. When baboon peripheral blood mononuclear cells (PBMC) or tissues were cocultured with the H-9 human T-cell line or the Raji human B-cell line, large multinucleated syncytia positive for SRV-2 antigens were observed microscopically. Immunoblot analysis of purified SRV Pc from cell culture supernatants demonstrated that the viral core and envelope proteins reacted with rabbit anti-SRV-2 serum. Fresh PBMC and cocultured cells were positive by polymerase chain reaction using two different sets of SRV-2 primers. Preliminary sequence analysis of two separate isolates from portions of the SRV-Pc p27 and gp20 regions revealed homology with SRV-1, SRV-2, and Mason Pfizer monkey virus. The homologies in the p27 segment were 91-94% and the homologies in the gp20 segment were 72-75%. PMID- 7871742 TI - Identification of residues in the N-terminal acidic domain of HIV-1 Vpr essential for virion incorporation. AB - Vpr is one of the auxiliary proteins encoded by the HIV-1 genome and is selectively incorporated into the virus particle. It has been shown that Vpr incorporation in the virus particle requires only the core protein Gag. In an effort to identify the domains of Vpr which are essential for incorporation into the HIV-1 virion, site-specific mutagenesis of vpr was carried out. Mutation of the highly conserved acidic residues in the N-terminal domain (amino acid positions 17-34) eliminated virion incorporation. These mutations disrupt a predicted amphipathic alpha-helical structure that is highly conserved among Vpr sequences. In contrast, alterations of the conserved cysteine (Cys76), basic domain (Arg87 and Lys95), and other residues (Gln65) did not impair the incorporation of Vpr into virus-like particles directed by HIV-1 Gag. The results presented here suggest that protein-protein interactions mediated through the putative helical domain of Vpr may participate in its incorporation into the virus particle. PMID- 7871743 TI - Nonpathogenic Nilaparvata lugens reovirus is transmitted to the brown planthopper through rice plant. AB - Nilaparvata lugens reovirus (NLRV) was found in a colony of the brown planthopper, N. lugens, an important plant virus vector. Unlike with usual phytopathogenic reoviruses, there are no visible symptoms on a rice plant which has been attacked by NLRV-infected planthoppers. Manner of transmission, host range, and multiplication of NLRV in rice plant were studied by enzyme-linked immunosorbent assay or polymerase chain reaction using reverse transcriptase. NLRV was transovumly transmitted to about 15% of nymphs. NLRV could further spread to planthoppers via rice plants through sucking by viruliferous insects. This horizontal transmission was apparently of primary importance for continuous NLRV infection to a colony of N. lugens. By corearing with viruliferous N. lugens on rice seedlings, Laodelphax striatellus acquired NLRV but Sogatella furcifera, Nephotettix cincticeps, and N. malayanus did not during the period studied. NLRV inoculated onto rice plant by viruliferous N. lugens failed to multiply, which accounts for the lack of symptoms on the plant even after an attack by viruliferous planthoppers. These biological properties and our previous data, which revealed a molecular similarity between NLRV and fijiviruses, suggest that NLRV is an ancestral virus of fijiviruses. PMID- 7871744 TI - An RNA-dependent RNA polymerase activity associated with virions of tomato spotted wilt virus, a plant- and insect-infecting bunyavirus. AB - An RNA-dependent RNA polymerase activity was found associated with virions of tomato spotted wilt virus (TSWV), a plant- and insect-infecting member of the family Bunyaviridae. Radiolabeled nucleoside triphosphates were incorporated into trichloroacetic acid-precipitable products by detergent-disrupted, purified TSWV virions. Incorporation was reduced to near-background levels when RNase was present in the reaction mixture. The predominantly double-stranded RNA products were RNase-resistant at high but not low salt concentrations. The activity required manganese and was independent of a DNA template. Discrete products of approximately 3.0 kb and heterogeneous smaller products were synthesized that hybridized to purified TSWV RNA and transcripts of cDNA clones encompassing parts of each of the three genomic RNAs. The predominant products were viral sense although significant amounts of viral complementary sense S RNA products were also synthesized. PMID- 7871745 TI - Use of highly conserved motifs in plant virus RNA polymerases as the tags for specific detection of carmovirus-related RNA-dependent RNA polymerase genes. AB - Two highly degenerate primers for sequence-specific amplification and cloning of a 510-nucleotide-long segment of RNA-dependent RNA-polymerase (RdRp) genes were selected and synthesized on the basis of available plant carmovirus-like viral RdRp sequences. These primers were shown to be efficient in PCR screening of different RdRp genes including those of carmoviruses, dianthoviruses, and tombusviruses. In particular, they were used for amplification, cloning, and sequencing of an RdRp gene fragment of an isometric plant virus with unknown evolutionary relationships, pelargonium flower break virus (PFBV). Alignment of the respective nucleotide and amino acid sequences indicates a very close similarity between PFBV and carnation mottle virus, the type member of carmoviruses. PMID- 7871746 TI - Identification and characterization of a 65-kDa protein processed from the gene 1 polyprotein of the murine coronavirus MHV-A59. AB - A 65-kDa protein has been detected in mouse hepatitis virus A59 (MHV-A59) infected DBT cells using polyclonal antibodies directed against polypeptides encoded by the 5' 1.8 kb of gene 1. The presence of this 65-kDa protein (p65) was previously predicted from immunoprecipitation studies of gene 1 expression in MHV A59-infected DBT cells with other antisera (1). p65 was rapidly labeled in virus infected cells at late times of infection; however, its cleavage from the polyprotein was significantly delayed compared to the amino-terminal gene 1 polyprotein cleavage product, p28. Similar to p28, p65 was cleaved from the growing polyprotein without detectable intermediate precursors. Kinetic analysis of p65 with specific antibodies indicates that p65 is immediately adjacent to p28 in the gene 1 polyprotein. The proteolytic activity responsible for the carboxy terminal cleavage of p65, as well as the function of the p65 protein, remains to be determined. PMID- 7871747 TI - Human and simian adenoviruses: phylogenetic inferences from analysis of VA RNA genes. AB - Adenovirus VA RNA genes have primary sequence constraints due to internal promoter regions and a high degree of secondary structure in the RNA product. To determine the relationships between human and simian adenoviruses, the VA RNA genes of several primate adenoviruses were characterized and compared to those sequences already published. Human adenoviruses of subgenera A, B:2, and F have only one VA RNA gene, whereas human adenoviruses of subgenera B:1, C, D, and E have two. The genomes of 12 monkey adenoviruses were found to have only one VA RNA gene, whereas the genomes of six representative chimpanzee adenoviruses were each found to have two VA RNA genes. Phylogenetic analysis of representative VA RNA gene sequences individually, irrespective of their strain of origin or partnering VA RNA gene, gave the following inferences. (1) The single VA RNA genes of human adenovirus subgenera A and F are most closely related to those of monkey adenoviruses. (2) The VA RNAI genes of human adenoviruses in subgenera B:1, D, and E, and also the single VA RNA genes of subgenus B:2 probably diverged from a common ancestral VA RNA gene. (3) This ancestral gene most likely reduplicated to give the precursor of all VA RNAII genes, the evidence for which has been almost totally lost in subgenus B:2 adenoviruses. (4) The two VA RNA genes of human subgenus C adenoviruses are relatively distant from each other phylogenetically. Since the Ad2 and Ad5 VA RNAI genes have a higher identity to the single VA RNA gene of SAV13 (SV36) than to those of any of the other human adenoviruses, these genes may have entered the human subgenus C adenovirus genome by substitution involving recombination with a simian adenovirus. The results of this study suggest that a renewed appraisal of VA RNA function in adenoviruses other than Ad2 and Ad5 may be necessary. PMID- 7871748 TI - A quail long-term cell culture transformed by a chimeric jun oncogene. AB - A chimeric construct (VCD) consisting of parts from viral jun, chicken c-jun, and chicken junD was cloned into the replication-competent retroviral RCAS vector. This construct, RCAS-VCD, was found to have a higher focus forming potential in quail fibroblasts than the equivalent construct RCAS-VJ-1, expressing viral jun. DNAs from RCAS-VCD and RCAS-VJ-1 were transfected into primary quail embryo fibroblasts. Cells derived from one RCAS-VCD-induced focus survived cell crisis, which became manifest after 15 passages, and could be expanded into a long-term culture. This cell line, termed VCD, has been passaged for over 100 times so far. The cells grow to very high densities and then pile up into clumps of rounded cells. The culture releases a transforming virus with a titer of 10(5) FFU/ml, as tested on primary quail embryo fibroblasts. The transformed phenotype of VCD cells was verified by agar colony formation. VCD cells are capable of anchorage independent growth with a cloning efficiency of 10%. Southern blot analysis of genomic DNA from VCD cells showed proviral integration of the RCAS construct without detectable rearrangements. Northern and Western blot analyses confirmed correct expression from integrated RCAS-VCD of predicted RNAs and of the chimeric Jun(VCD) protein. jun(VCD)-transformed cells provide a constant source of homogeneous cellular material for the investigation of the molecular mechanisms of jun-induced cell transformation and for the identification of direct and indirect targets of Jun protein function. PMID- 7871749 TI - Comparative nucleotide and amino acid sequence analysis of the sequence-specific RNA-binding rotavirus nonstructural protein NSP3. AB - NSP3, an acidic nonstructural protein, encoded by gene 7 has been implicated as the key player in the assembly of the 11 viral plus-strand RNAs into the early replication intermediates during rotavirus morphogenesis. To date, the sequence of NSP3 from only three animal rotaviruses (SA11, SA114F, and bovine UK) has been determined and that from a human strain has not been reported. To determine the genetic diversity among gene 7 alleles from group A rotaviruses, the nucleotide sequence of the NSP3 gene from 13 strains belonging to nine different G serotypes, from both humans and animals, has been determined. Based on the amino acid sequence identity as well as phylogenetic analysis, NSP3 from group A rotaviruses falls into three evolutionarily related groups, i.e., the SA11 group, the Wa group, and the S2 group. The SA11/SA114F gene appears to have a distant ancestral origin from that of the others and codes for a polypeptide of 315 amino acids (aa) in length. NSP3 from all other group A rotaviruses is only 313 aa in length because of a 2-amino-acid deletion near the carboxy-terminus. While the SA114F gene has the longest 3' untranslated region (UTR) of 132 nucleotides, that from other strains suffered deletions of varying lengths at two positions downstream of the translational termination codon. In spite of the divergence of the nucleotide (nt) sequence in the protein coding region, a stretch of about 80 nt in the 3' UTR is highly conserved in the NSP3 gene from all the strains. This conserved sequence in the 3' UTR might play an important role in the regulation of expression of the NSP3 gene. PMID- 7871750 TI - Interspecific reassortment of genomic segments in the evolution of cucumoviruses. AB - Segmented genomes of RNA viruses are thought to evolve and be maintained in analogy to sexual recombination and reassortment in eukaryotic systems. If reassortment among genomes is an important event in cucumoviral evolution, then such events should be detectable among extant viruses. In this study, phylogenetic analyses of cucumoviruses were performed using aligned amino acid sequences. The results reveal different relationships among species when the three genomic segments are compared, suggesting that reassortment events have given rise to extant forms. In addition, we describe a cucumovirus isolate that is composed of genomic segments from two distinct viral species. These results indicate that reassortment events may provide a mechanism for speciation in cucumoviruses. PMID- 7871751 TI - HIV-1 Nef protein downregulation of CD4 surface expression: relevance of the lck binding domain of CD4. AB - HIV Nef protein downregulates the surface expression of CD4 on T-cells but its mechanism of activity is unknown. We have analyzed the relevance of different portions of the CD4 molecule with respect to the activity of Nef. Upon transfection of Jurkat T-cells that express Nef or do not express Nef with constructs that include different domains of the CD4 molecule, we demonstrated that Nef downregulation of CD4 requires the first 30 amino acids of the CD4 cytoplasmic tail and that the lck-binding domain of CD4 was at least partially responsible for this effect. Furthermore, upon transfection of U-937 cells with an lck-expressing plasmid we showed that CD4 downregulation by Nef is significantly more efficient when lck is present. Finally, by measuring the rate of CD4 endocytosis by a novel flow cytometric method we showed that the effect of Nef on CD4 surface expression resulted from accelerated CD4 internalization. PMID- 7871752 TI - The reovirus mutant tsA279 has temperature-sensitive lesions in the M2 and L2 genes: the M2 gene is associated with decreased viral protein production and blockade in transmembrane transport. AB - Temperature-sensitive mutants provide an ideal means for dissecting viral assembly pathways. The morphological variants produced by and biological characteristics of tsA279, a previously uncharacterized mutant from the Fields' panel of temperature-sensitive mutants of reovirus, were determined under restrictive growth conditions. The mutant showed a distinctive pattern of increased temperature sensitivity as the temperature was raised from 39 degrees to 40 degrees. Wild-type reovirus type 1 Lang and the mutant were crossed to generate reassortants. Efficiency of plating analyses of the reassortants showed that tsA279 has temperature-sensitive lesions in two genes, a mildly temperature sensitive one in L2, which encodes core spike protein lambda 2, and a stronger, dominant lesion in M2, which encodes major outer capsid protein mu 1. Electron microscopic examination of thin-sectioned tsA279-infected cells showed three ways in which the mutant phenotypes were expressed. The mutant appeared to be blocked in transmembrane transport of virions, a phenotype that mapped to the M2 gene; the mutant produced significantly reduced amounts of identifiable particles; and those particles that were produced appeared to be morphological variants. Immunofluorescent microscopy and immunoprecipitations of tsA279- and various T1L x tsA279 reassortant-infected cells suggested that the reduction in observed progeny was caused by a decreased production of viral proteins at the nonpermissive temperature. This phenotype also mapped to the mutant M2 gene. PMID- 7871753 TI - Growth-restricted dengue virus mutants containing deletions in the 5' noncoding region of the RNA genome. AB - The dengue type 4 virus (DEN4) RNA genome contains a 101-nt 5' noncoding (NC) sequence which is predicted to form a stable secondary structure. DEN4 cDNA from which infectious RNA can be transcribed was used to engineer deletions in the 5' NC region for functional analysis of RNA structure and for isolation of DEN4 mutants that could be evaluated as candidates for use in a live attenuated vaccine. Eleven distinct deletions in the region of the DEN4 genome between nts 18 and 98 were constructed; each mutation was predicted to alter or disrupt the local base-parings in the 5' NC RNA structure. An infectious virus was not recovered from the RNA transcripts of five of these deletion mutants. Significantly, four of the five apparently lethal deletions were located in a 5- to 6-nt base-paired region of a predicted long stem or adjacent to it. In contrast, with one exception, mutants which yielded infectious virus had deletions which were located in a loop or short stem region. The effect of the deletions on the efficiency of translation of viral RNA transcripts was examined in vitro. The RNA transcripts of deletion constructs which did not yield viable virus were translated at an efficiency ranging from 40 to 160% that of wild-type virus transcripts. The translation efficiency of infectious RNA transcripts also varied. Deletion mutants recovered from RNA transcripts that exhibited low to moderate efficiency of translation had a small plaque morphology and exhibited reduced growth in simian LLC-MK2 and mosquito C6/36 cells compared to the wild type virus. Among the 11 mutant constructs, deletion of nts 82-87 caused the greatest reduction in translation efficiency. Nevertheless, an infectious virus was recovered from LLC-MK2 cells transfected with the RNA transcripts of mutant d(82-87). The progeny of this mutant produced small plaques on LLC-MK2 cells and grew to low titer in these cells. Unlike wild-type DEN4 or other DEN4 deletion mutants tested, mutant d(82-87) failed to produce plaques on C6/36 cells and was also replication-defective in Aedes aegypti and Aedes albopictus following intrathoracic inoculation. PMID- 7871754 TI - Oct-1 activates the epithelial-specific enhancer of human papillomavirus type 16 via a synergistic interaction with NFI at a conserved composite regulatory element. AB - A highly conserved composite regulatory element in the epithelial-specific enhancer of human papillomaviruses (HPVs) consists of an octamer motif separated by exactly 2 bp from a nonpalindromic NFI site. Point mutations within this composite element, created to prevent the binding of Oct-1 or NFI, result in up to 10- to 12-fold decrease in enhancer activity. A mutation preventing the binding of both proteins does not, however, result in any further decrease in activity suggesting a cooperative interaction between these two factors. Electrophoretic mobility shift assays provide evidence that the simultaneous binding of both factors to the composite element is indeed required for efficient activation. Furthermore, evidence demonstrating the inability of Oct-1 by itself to elicit a transcriptional response from this enhancer position suggests that Oct-1 does not activate transcription directly, but rather may play a crucial role in the viral enhancer by tethering NF1 to the composite element. This finding represents both a potentially important mechanism by which HPV gene expression can be regulated and an interesting model for the study of transcriptional cooperativity. PMID- 7871755 TI - Assembly of the T = 4 Nudaurelia capensis omega virus capsid protein, post translational cleavage, and specific encapsidation of its mRNA in a baculovirus expression system. AB - We have expressed the gene encoding the coat protein (CP) of Nudaurelia capensis omega virus in insect cells with a baculovirus vector. Expression of CP resulted in formation of virus-like particles (VLPs) having a size consistent with the T = 4 quasi-symmetry observed for native virions. This is the first demonstration of assembly for a T = 4 particle, with chemically identical subunits present in four distinct environments, by heterologous expression. Initial yields of VLPs were low, and an efficient one step nondenaturing procedure involving separation on discontinuous glycerol gradients was developed. Using this method, VLPs were obtained in quantities sufficient for further characterization. Electron microscopic observation revealed 40-nm particles that were morphologically similar to native virus. SDS-PAGE revealed that these particles were composed of a 62-kDa major protein and a minor 70-kDa protein. Pulse-chase experiments revealed that the larger species was processed into the smaller one very slowly over the course of an infection. It was also determined that this cleavage was apparently dependent on release of these particles from the cell. Furthermore, these particles were found to encapsidate the polyhedrin promoter-directed CP mRNA with an apparently striking degree of specificity and selectivity. This investigation establishes that a specific encapsidation signal exists within the CP coding sequences and that the components required for reconstructing most, if not all, steps in the morphogenesis of this virus can be accomplished in baculovirus-infected cells. The results presented here are consistent with the belief that similar biological strategies are utilized by T = 3 nodaviruses and T = 4 tetraviruses in particle assembly. PMID- 7871756 TI - Hepatitis B virus enhancer binds and is activated by the Hepatocyte nuclear factor 3. AB - The enhancer of hepatitis B (HBV) virus displays a liver-specific activity that determines the postreceptor virus-host tropism. Despite the detailed study of this enhancer our knowledge of the mechanisms underlying this behavior is very limited. Here we report that the hepatocyte nuclear factor 3 (HNF3) is at least in part responsible for the liver-specific activity of the enhancer. We demonstrate that recombinant HNF3 alpha binds the enhancer at two sites with different affinity. Transfection studies have demonstrated that the enhancer is active only in liver cells and that integrity of the HNF3 binding sites is important for its full activity. In vitro transcription assays revealed that the enhancer is active only in liver extracts but not in extracts prepared from HeLa cells. Furthermore, the latter extract cannot be activated by addition of recombinant HNF3 alpha. A similar behavior is manifested in transfected cells and, here again, the inactive enhancer is not activated by cotransfected HNF3 beta and alpha. Collectively, our study shows that HNF3 activators are required but not sufficient for full activation of the HBV enhancer and there is a need for additional liver-specific activators or coactivators. PMID- 7871757 TI - Analysis of the transcription pattern of HSV-1 UL52 and UL53 genes. AB - The UL52 and UL53 genes of herpes simplex virus type-1 are both located in the BamHI-L DNA fragment, with an overlap of 14 amino acids. An RNase protection experiment was designed to determine the 5' termini of both the UL52 and UL53 mRNAs. The 5' end of the UL52 mRNA was found to be located 100 bp upstream of its ATG initiation codon. Surprisingly, the 5' terminus of the UL53 gene was found to be downstream of its putative initiation codon. Therefore, it was suggested that the translation of the UL53 open reading frame (ORF) starts at an internal initiation codon that is located 55 codons downstream of the putative one. A hybrid selection experiment was performed in which the UL53-specific mRNA was selected from BSC-1 cells infected with HSV-1 KOS and translated in vitro. The translation product of the UL53 message was found to be 32 kD (shorter than the original 37.5 kD ORF). The size of the protein obtained corresponds with the expected translation product starting at the downstream initiation codon. Analysis of the sequence upstream of this initiation codon reveals the presence of a promotor sequence. Therefore, we suggest that the UL53 protein is 54 amino acids shorter than was previously suggested and is located at coordinates 112,341 113,193. PMID- 7871758 TI - A new Chinese isolate of hepatitis E virus: comparison with strains recovered from different geographical regions. AB - The full-length cDNA of a new Chinese strain (KS2-87) of Hepatitis E virus (HEV) has been constructed and sequenced. The 5' noncoding region of KS2-87 is 26 nucleotides in length, which is one nucleotide shorter than that of HEV (B1) (Burma) and 23 nucleotides longer than that of HEV (Mexico). Comparison of the nucleotide and amino acid sequences of KS2-87 with all other published HEV sequences showed that KS2-87 was closer to two other Chinese strains (CHT-88, CHT 87) and SAR-55 (Pakistan) than to HEV (B1) and HEV (B2) (Burma) or HEV (Mexico). Comparisons of partial sequences of genes encoding a nonstructural and a structural protein revealed the existence of genetically related groups of HEV within geographical regions, whereas larger nucleotide differences were seen among isolates that were more geographically and epidemiologically distant. PMID- 7871760 TI - A novel explanation for the existence of open reading frames on latency associated transcripts of alphaherpesviruses. AB - Recent studies indicate that alphaherpesviruses express latency associated transcripts (LATs) from the antisense strand of immediate early (IE) genes of the viral genome. It has been discussed that LATs containing extended open reading frames (ORFs) might be translated into protein products. We found that a salient feature of some herpesvirus DNAs is a high GC preference at the third codon positions. As a consequence, the probability of a stop codon arising at two of the six frames of the DNA strand is very low. The regions missing stop codons frequently start with ATG, resulting in extended ORFs. Therefore, the presence of a gene-long ORF does not necessarily mean that it is relevant to real translation. PMID- 7871759 TI - Dengue fever virus and Japanese encephalitis virus synthetic peptides, with motifs to fit HLA class I haplotypes prevalent in human populations in endemic regions, can be used for application to skin Langerhans cells to prime antiviral CD8+ cytotoxic T cells (CTLs)--a novel approach to the protection of humans. AB - Flaviviruses were reported to induce CD8+ cytotoxic T cells in infected individuals, indicating that nonapeptides, proteolytic cleavage products of the viral precursor protein, enter the endoplasmic reticulum in infected cells and interact with HLA class I molecules. The assembled HLA class I molecules are transported to the plasma membrane and prime CD8+ T cells. Current knowledge of the interaction of viral peptides with HLA molecules is reviewed. Based on this review, an idea is presented to use synthetic flavivirus peptides with an amino acid motif to fit with the HLA class I peptide binding group of HLA haplotypes prevalent in a given population in an endemic area. These synthetic viral peptides may be introduced into the human skin using a lotion containing the peptides ("Peplotion") together with substances capable of enhancing the penetration of these peptides into the skin to reach Langerhans cells. The peptide-treated Langerhans cells, professional antigen-presenting cells, may bind the synthetic viral peptides by their HLA class I peptide-binding grooves. Antigens carrying Langerhans cells are able to migrate and induce the cellular immune response in the lymph nodes. This approach to the priming of antiviral CD8+ cytotoxic T cells may provide cellular immune protection from flavivirus infection without inducing the humoral immune response, which can lead to the shock syndrome in Dengue fever patients. To be able to develop anti-Dengue virus synthetic peptides for populations with different HLA class I haplotypes, it is necessary to develop computational studies to design HLA class I Dengue virus synthetic peptides with motifs to fit the HLA haplotypes of the population living in an endemic region for Dengue fever. Experiments to study Dengue virus and Japanese encephalitis peptides vaccines and their effectiveness in protection against Dengue fever and Japanese encephalitis are needed. The development of human antiviral vaccines for application of viral peptides in a lotion to human skin ("Peplotion") may be useful and affordable for populations of developing countries. PMID- 7871761 TI - Characterization of a Marek's disease virus mutant containing a lacZ insertion in the US6 (gD) homologue gene. AB - We report the construction of a Marek's disease virus (MDV) mutant containing the lacZ gene of Escherichia coli inserted into a homologue of the US6 (glycoprotein D, gD) gene of herpes simplex virus. The mutant was constructed using the high passage GAatt85 MDV strain as the parent virus, since that strain grows readily in chicken embryo fibroblasts using culture conditions conducive to mutant virus construction. The lacZ insertion site was positioned one third of the way into the US6 (gD) open reading frame. Insertion of the lacZ gene disrupted a major 6.2 kb transcript that initiated approximately 2.5 kb upstream of the gD homologue gene in the vicinity of the US3 homologue and sorf4 genes, and extended into the US7 (gI) homologue gene. The mutant virus (US6lac) and the parent virus had similar growth kinetics in cell culture at 37 degrees C and 41 degrees C. Furthermore, the US6lac mutant could be reisolated from the spleens and peripheral blood of infected chickens with a frequency comparable to that of the parent virus. Our results indicate that the gene encoding the gD homologue is nonessential for growth in cell culture or for infection of chickens following intra-abdominal inoculation with an attenuated serotype-1 MDV. PMID- 7871762 TI - Glycoprotein B of bovine herpesvirus type 4: its phylogenetic relationship to gB equivalents of the herpesviruses. AB - In order to estimate the phylogenetic relationship of BHV-4 among the herpesviruses, we have cloned and sequenced its glycoprotein B (gB). The 2.6 kb open reading frame codes for a 874 amino acid long protein. The comparison of its deduced amino acid sequence with those of its counterparts in 19 distinct herpesviruses groups BHV-4 into the gamma-herpesvirinae. The calculation of an evolutionary tree emphasized that BHV-4 is more closely related to herpesvirus saimiri (HVS) than to Epstein-Barr virus (EBV). However, in contrast to EBV and HVS, the gB of BHV-4 contains a putative protease cleavage site and 20 potential N-glycosylation sites. The alignment of the amino acid sequences revealed that 10 cysteine and 7 proline residues, as well as the motifs SPF and GQLG, were completely conserved among the 20 investigated gBs. PMID- 7871763 TI - Molecular characterization and determination of the coding capacity of the genome of equine herpesvirus type 2 between the genome coordinates 0.235 and 0.258 (the EcoRI DNA fragment N; 4.2 kbp). AB - The complete DNA nucleotide sequence of the EcoRI DNA fragment N (0.235 to 0.258 viral map units) of equine herpes virus type 2 (EHV-2) strain T400/3 was determined. This DNA fragment comprises 4237 bp with a base composition of 55.23% G+C and 44.77% A+T. Nineteen open reading frames (ORFs) of 50-287 amino acid (aa) residues were detected. ORF number 10 is located between the nucleotide position 2220 and 2756 coding for a protein of 179 amino acid residues. This protein shows significant homology to the cytokine synthesis inhibitory factor (CSIF; interleukin 10) of human (76.4%) and mouse (68.5%), and to the Epstein-Barr virus (EBV) protein BCRF1 (70.6%). The existence of an interleukin 10 (IL-10) analogous gene within the genome of the EHV-2 was confirmed by screening the genome of nine EHV-2 strains using specific oligonucleotide primers corresponding to the 5' and 3' region of this particular gene by polymerase chain reaction. In all experiments an 870 bp DNA product was amplified. The specifity of the amplified DNA fragments obtained from individual EHV-2 strains was confirmed by DNA-DNA hybridization experiments. The DNA sequence analysis of the amplified DNA products of the EHV-2 strain LK was carried out. This analysis revealed the identity of the corresponding IL-10 gene (540 bp) of this strain to the IL-10 gene of EHV-2 strain T400/3. The presented data indicate that the EHV-2 genome harbors a viral interleukin 10-like gene. This is further evidence that the IL-10 gene can be present in the genomes of members of the Herpesviridae family. PMID- 7871764 TI - Molecular cloning and nucleotide sequence of the coat protein gene of a Cuban isolate of potato leafroll virus and its expression in Escherichia coli. AB - Total RNA from infected Physalis floridana was isolated to generate complementary DNA corresponding to the coat protein (GP) gene of a Cuban isolate of potato leaf roll virus (PLRV). This cDNA was amplified by the polymerase chain reaction (PCR) and cloned into the bacterial expression vectors pEX(1-3) for fusion protein expression in E. coli. The product was detected by antibodies specific for the PLRV CP. The coding sequence of the CP gene was determined, and the predicted length of the CP was 208 amino acids (23 kD). The nucleotide sequences and deduced amino acid sequences were compared with the other PLRV isolates and found to be 97-99.5% identical at both the nucleotide and amino acid sequence level of other isolates. Comparison of the deduced amino acid sequences of the PLRVcub CP revealed considerable homology to other luteoviruses. We believe that the protocol described could be applicable to other plant viruses of low abundance or of cumbersome isolation, since this method is less time consuming than the traditional methods of cloning coat protein genes of plant viruses with known sequences. PMID- 7871765 TI - Sequence variation of human papillomavirus type 16 E7 in preinvasive and invasive cervical neoplasias. AB - Variation in the nucleotide sequence of the HPV 16 E7 gene in preinvasive cervical intraepitherial neoplasia (CIN) and invasive cervical carcinoma specimens was analyzed. Direct DNA sequencing of PCR-amplified products with primers different from those used for PCR with 5'-end labeling generated distinct sequence ladders with a low background, even in specimens containing relatively low copy numbers of HPV. Of 14 cervical neoplasias, 11 cases showed sequence diversity from prototype HPV16, and a total of 22 nucleotide exchanges were detected. Nine of these led to single amino acid exchanges: [Thr5] to [Lys5] in one case and [Asn29] to [Ser29] in eight cases. The [Ser29] E7 was distributed uniformly among invasive carcinomas and precancerous legions, and was also found in a normal cervix. The [Lys5] E7 and [Ser29] E7 had transforming potential similar to the prototype E7 assessed by cooperation with the activated ras gene in rat embryo fibroblasts. PMID- 7871767 TI - [New sour dairy products for children and diet regimen]. AB - The paper is concerned with principal know-how aspects in production of sour milk food for infants and subjects on diet. Ingredients of dry (Rostok, Rostok 1) and liquid (Kislomolochny, Biolact) mixtures are listed. Increased production of the above food will help to meet the requirement of children and diet-keeping adults in dairy produce in Russia. PMID- 7871766 TI - Analysis of the genetic variability of maize streak virus. AB - The nucleotide sequences of the small intergenic region (SIR) and the gene encoding the coat protein of 12 maize streak virus (MSV) isolates from different geographic locations have been determined. These have been used to assess the variability of the virus and to construct evolutionary dendrograms. For the viruses analyzed, the maximum levels of sequence divergence were found to be 10.9% and 2.0% at the nucleotide and amino acid levels, respectively. A genetically distinct strain of MSV was collected from islands in the Indian ocean. The significance of these findings for detection of the virus in epidemiological studies and breeding of resistant plant varieties is discussed. PMID- 7871768 TI - [Benz(a)pyrenes and N-nitrosamines in dry dairy products]. AB - Results of works induding study of effect of different factors (environment, type of equipment, technology) on content of cancerogenic substances in dry milk products were summarized. Possible reasons of appearance of cancerogens in milk in process of drying were determined, dataes of concentration of benz(a)pyren and N-nytrozamens in milk and warmth carrier before and after drying were established. Explanation of separate appearances which connect with change of quantity of cancerogens in product on different stages of drying was suggested. PMID- 7871769 TI - [Rare food poisoning outbreak]. PMID- 7871770 TI - [Effect of zinc in diet on course of chronic cadmium intoxication in experiment]. AB - Effect of content of optimum (0.0009%), excessive and deficiency (0%; 0.00045%) quantities of zinc in alimentary diet on process of cadmium intoxication was studied in chronic experiment with rats. It was established that degree by content of zinc in organism influenced on process of chronic cadmium intoxication very much. Degree by intoxication increased in consequence of deficiency of zinc content in diet as including to diet optimum or excessive quantities of zinc protected or decreased from lesion of liver, kidneys and testis inducing effect of cadmium. PMID- 7871771 TI - [Effect of trans-anethole on liver monooxygenase system and its induction of polychlorinated diphenyls]. AB - Effect of trans-anetol (t-An) as nutritive addition to cytochrome P-450 containing system (MOS) of liver of rats was studied. It was shown, that t-An rendered inducing action to MOS, which depended on degree of action. It was established that simultaneous effect of t-An and mixture of polychlorinated diphenyles (sovol) modified inducing action of sovol to cytochrome P-450 system, Simultaneous effect of t-An and mixture of polychlorinated diphenyles increased hepatotoxic action of these xenobiotics. PMID- 7871772 TI - [Biologically active garlic compounds and perspectives of their use in the therapeutic and prophylactic diet (review)]. AB - Therapeutic action of garlic and garlic's preparations at diseases of vessels and heart, organs of digestion, breachs of lipid exchange and system mycosis was connected with presence of complex of sulfur contain compounds:thiosulfinates, dialkilsulfides, dithiins, adgoens, thioglycosidepeptides. These compounds were picked out from garlic or synthesired rendered corresponding action to blood's properties, metabolism and infection processes in organism. Garlic preparations in composition of products of nutrition can be effective for different system of prophylactice nutrition and dietotherapy. Scientific and technical dataes were essential for preparation of technology of new products from garlic. PMID- 7871773 TI - [Ascorbic acid in plants, cultivated on the closed soil with the use of zeolite]. PMID- 7871774 TI - [Immune and metabolic effect of polyunsaturated fatty acids omega 3 in anti atherosclerotic diet in the treatment of patients with ischemic heart disease, familial hyperlipoproteinemia and hypertension]. AB - Effect of antiatherosclerotic diet of 112 patients with cardioishemic disease IIa, IIb, and IV types was observed. Positive dynamics of clinical picture of disease, values of lipid metabolism and T-cell cents immunity were shown, particularly for patients with hyperlipidemy, which developed as result of effect of medium cents and genetic cents factors. Including to antiatherosclerosis diet polyunsaturated fatty acids of family (w-3) intensified hypolipidemic effect. PMID- 7871775 TI - [Current news in the prevention and treatment of atherosclerosis]. PMID- 7871776 TI - [Supplements to the "Medical and biologic requirements and sanitary standards of quality of food and food products". Food additives]. PMID- 7871777 TI - [Vitamin and mineral enrichment of wheat flour of the high and first class quality]. AB - Norms of inclusion of vitamins (B1; B2; PP) and mineral substances (Ca and Fe) in high and first-rate wheat's flour were defined. Vitamin's contents were verified and composed balance of vitamins and mineral substances contents in different stages of technology process. It was established efficacy of enrichment of wheat's flour with vitamin-mineral mixture to production as fast as possible, particularly in regions of Chernobil's accident and also in regions with ferrum deficiency. PMID- 7871778 TI - [The effect of a promoter P28-1 of Bacillus subtilis on Streptomyces differentiation]. AB - A 1.1kb promoter P28-1 was inserted into pUC19. After then, the P28-1 was subcloned into the HindIII-EcoRI sites of the high copy number Streptomyces promoter probe plasmid pIJ4083 containing xy1E reporter gene. This recombinant plasmid was designated as pIJ4498. When pIJ4498 was introduced into Streptomyces coelicolor J1501 protoplasts, transformants conferred a white phenotype, whereas the vector pIJ4083 gave rise to colonies of normal, dark grey appearance which is the same as that of J1501 itself. After confirming pIJ4498 structure with some restriction enzymes, it was also introduced into whiG mutant (C71). Crude enzyme extracts were isolated from J1501/pIJ4498, J1501/pIJ4083 and C71/pIJ4498 respectively, the crude enzyme extract from J1501/pIJ4498 could oxidize catechol (colourless) to 2-hydroxy muconic semialdehyde (yellow colour), but crude enzyme extracts from J1501/pIJ4083 and C71/pIJ4498 could not oxidize catechol to 2 hydroxymuconic semialdehyde. The results indicated that P28-1 might be recognised by sigma whiG RNA polymerase, and activated the xylE reporter gene expression and reduced J1501 sporulation. PMID- 7871779 TI - [The effect of Sindbis virus multiplication on gene expression of host cells]. AB - Sindbis virus (SBV) infection mediated a rapid shutoff of host cellular gene expression (mRNA synthesis and protein synthesis); however the synthesis of cellular rRNA remained at the same level as the uninfected cells. Meanwhile a cellular protein P105 was shown to be enriched in the nuclear matrix. Actionmycin D treatment after virus infection resulted in an apparent reduce in the production of viral structural proteins and infectious virions. The results presented here not only demonstrated the complexity of SBV-mediated regulation of host gene expression, but also suggested SBV nonstructural protein nsP2 and capsid protein C were possibly involved in this process. PMID- 7871780 TI - [A novel extended-spectrum beta-lactamase in a ceftazidime-resistant isolate of E. coli]. AB - A novel extended-spectrum beta-lactamase (ESbla) encoded on a plasmid of approximately 7.5kb, conferring resistance to beta-lactams tested except cefoxitin and imipenem, was found in a ceftazidime-resistant isolate of E. coli form our hospital. The resistance to beta-lactams was transferred by conjugation to E. coli JP559 together with the aminoglycosides and sulfonamide resistance. Clavulanate, one of beta-lactamase inhibitors, inhibited its activity. This ESbla gene hybridized neither with an intra-genic fragment of SHV-1 nor with that of TEM-1. The molecular origin of that novel ESbla needed to be further studied. PMID- 7871781 TI - [Rumen bacteria degrading toxic mimosine and dihydroxypyridine compounds in China]. AB - Four anaerobic strains were isolated from the rumen of the cattle which no specific toxic symptoms were seen when Leucaena was fed in Weizhou island Beihai city, Guangxi Province, China. All of these strains (BR-1, BR-2, BR-5 and BR-7) possess degradative activities to toxic mimosine, 3-hydroxy-4 (1H) -pyridone (3, 4-DHP) and 2, 3-dihydroxypyridine (2, 3DHP) from Leucaena, that were confirmed by analysis of HPLC. Pure and mixed cultures of these four strains in vitro degraded 44-59% of mimosine, 30-47% of 3, 4 DHP, and 58-60% of 2, 3 DHP respectively in 3 days. Strains of Both BR-1 and BR-2 were almost identical and were characterized as Lactobacillus, may be a new species. Strains of BR-5 and BR-7 were characterized as Streptococcus bovis and Clostridium sporogenes respectively. It has not yet been reported that these Gram positive facultatively and obligately anaerobic bacteria were able to degrade mimosine, 3, 4 DHP and 2, 3 DHP. These detoxic bacteria were existing in the rumen microflora of cattle in Weizhou island, protecting therefore their hosts animal from Leucaena toxicity. PMID- 7871782 TI - [Immunological cross-reaction of serotype I Marek's disease virus 38kD phosphorylated protein with serotype II and III viruses]. AB - Marek's disease virus (MDV) 38kD phosphorylated protein (pp38), which was identified by monoclonal antibody (mAb) H19 specific to pathogenic serotype I of MDV, has been recognized as a transformation-associated antigen specific to serotype I of MDV. The recombinant pp38 was prepared and purified from pp38 expressing recombinant baculovirus infected Sf9 cell lysates through a mAb H19 affinity column. In indirect fluorescence antibody test, the mouse sera against the purified recombinant pp38 not only gave a high titer to serotype I strain GA infected CEF but also gave a reasonable titers to serotype II strain Z4- and serotype III HVT strain Fc126-infected CEF. In another way, the pp38- expressing recombinant baculovirus infected Sf9 cells reacted with anti-serotype I MDV chicken sera as well as with anti-serotype II and serotype III MDV chicken sera respectively. The results imply that both serotypes II and III of MDV probably contain a homologue to pp38 of serotype I. PMID- 7871783 TI - [Retrospect on 24 years of the Pathological Institute]. PMID- 7871784 TI - [Nephroprotection by inhibition of the renin-angiotensin system--wish or reality?]. AB - Angiotensin converting enzyme (ACE) inhibitors are used with increasing frequency in the treatment of hypertension in patients with chronic renal disease. In experimental models of chronic renal failure and, recently, in patients with diabetic nephropathy ACE inhibitors have also been shown to be effective on long term administration in slowing the progression of renal failure. The exact mechanisms of this nephroprotective effect are not yet fully understood, but changes in hemodynamic parameters, a reduction of proteinuria and an inhibition of glomerular cell proliferation appear to be involved in preventing glomerulosclerosis. PMID- 7871786 TI - [Medical informatics in research, teaching and patient management]. AB - The field of medical informatics in its current understanding is defined and criteria distinguishing this field from similar areas are provided. Special consideration is given to its position at a School of Medicine - in particular to the University of Vienna Medical School with the Vienna General Hospital as its teaching hospital. Demands for medical informatics and electronic data processing (EDP) in this extended field of activity come from four different sources: (1) research in medical informatics, (2) teaching of medical informatics as well as EDP training, (3) EDP service for research and teaching, and (4) EDP hospital operations to assist patient care. (Purely administrative EDP demands are not considered here.) It is shown that the different demands can be fulfilled by the usually available institutions involved in medical informatics and EDP at a School of Medicine. At many places these institutions are as follows: (1) a department or division of medical informatics with a possibly attached computer center dedicated to provide assistance in the area of research and teaching, (2) the computer center of the respective university the School of Medicine belongs to, (3) the computer center of the hospital-owned institution responsible for all EDP activities connected to patient care, and (4) external software companies and EDP training centers. To succeed in the development of an exhaustive, school-wide system of medical informatics and EDP that considers the different demands in research, teaching, and EDP hospital operations equally, close and well-suited coordination between the institutions involved is necessary. PMID- 7871785 TI - [Fragments of human chorionic gonadotropin (hCG): diagnosis of pregnancy and tumors]. AB - The pregnancy and tumor marker human chorionic gonadotropin (hCG) belongs to the family of the glycoprotein hormones. Information on epitope forming sequences of hCG and its subunits hCG alpha and hcg beta has significant impact on the examination of intra- and extracellular metabolism and the standardization of diagnostic assay systems. Variants of hCG appear in biological fluids with variable modifications on different parts of the molecule. These changes may influence the binding patterns of monoclonal antibodies (MCA), thereby causing erroneous results in hCG immunoassays. The aim of the present work was to investigate the influence of peptide bond cleavages and the loss of certain segments of the molecule, which were induced by proteases on the expression of the seven hCG alpha-(alpha 1-alpha 7), nine hCG beta- (beta 1-beta 9) and four hCG beta-core-fragment-epitopes (beta 10-beta 13), previously identified by us [1 10]. To this end, we digested hCG alpha and hCG beta with chymotrypsin. Hormone fragments were separated by high performance liquid chromatography (HPLC) and subsequently immunochemically examined by direct binding radioimmunoassay (DB RIA), competitive RIA and immunoenzymometric assays (IEMA). Fractions containing hCG-like immunoreactivity were sequenced by Edman and carboxypeptidase-Y degradation. It appeared that: (I) Amino acids (AA) alpha 41-47 and the peptide bonds between AA alpha 40/41, alpha 47/48 and alpha 29/30 do not influence the expression of the 7 alpha-epitopes, (II) The absence of the hCG beta N-terminus plays a crucial role for the formation of epitopes beta 10 and beta 13. (III) Neither the presence nor the absence of the C-terminal peptide of hCG beta (hCG beta CTP, AA beta 114-145) has any importance for the expression of epitopes beta 1-beta 7 and beta 10-beta 13 (IV).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871787 TI - [The psychology of interpersonal communication]. AB - The concept of the "Nachrichtenquadrat" tries to analyse messages and splits them into 4 aspects. Besides the information-part there is always a message of relation involved, as well as a kind of selfdisclosure and sometimes an appeal to the address. Corresponding the same 4-dimensional view is applied to the "ears" of the one who receives a message. PMID- 7871788 TI - [Medical correspondence]. AB - This paper gives a short overview of the most relevant elements of medical records. It seems important to emphasise, that writing a letter to the family doctor has more meaning than simple documentation. It is a matter of communication, involving psychological and ethical requirements. Professional discretion, the right length of the letter, as well as focusing at the real important issues are further aspects of successful records. PMID- 7871789 TI - [Continued medical education from the viewpoint of the established physician]. AB - From the point of view of the General Practitioner continuous medical training of today still is in many aspects insufficient. Mainly the choice of the topics is not oriented at the real training needs of the G.P. and has only poor relationships to every day practice. There are rather no possibilities of an active involvement of the G.P. and a lot of sessions are still carried out by speakers with a special clinical experience. It seems that the peer review groups will be one of the most successful forms of continuous training in the future. It leads to an active co-operative training among C.P.'s, totally realize to every days practice and leads to a more standardized and better care of the patient. PMID- 7871790 TI - [Communication structures in the medical clinic]. AB - Medical communication is a matter of great importance, however is if often overlooked. Within the clinical context communication is frequently structured e.g. the daily conferences. This paper tries to analyze the structures and to identify the different motivations of medical communication. The goal is to improve effectiveness through structure without loosing dialogic chances. PMID- 7871791 TI - [Institutionalized communication]. AB - This paper is analysing the psychological interaction of communication and institutions. Seeking power and success are mentioned as important motivation factors. The personal situation as lecturer is interpreted as an example of psychological relations within structured communication. PMID- 7871792 TI - [The Balint group: analysis of the physician-patient relationship. A medical discussion in the group]. AB - It is given a short introduction about the method of the work of Balint-groups. The importance of this method for the graduate medical education and further medical development is described. The differentiation between psychotherapeutical supervision groups and the discussion of cases in general are illustrated. Michael Balint is introduced. PMID- 7871793 TI - [Teaching and learning in medicine--or: how does one become a physician?]. AB - Since the beginning of a formalized medical education in the high Middle Ages continue to be discussed in principle three hypothesis how an effective doctor should be trained: by organizing an ingenious program of studies, by canonizing the content of knowledge, or by taking in consideration the demand of public utility. All three viewpoints produced typical forms of communication within the teaching of medicine, without finding an ideal type until today. PMID- 7871794 TI - [Language use in medicine]. AB - Language is a main constituent of communication. To understand its signs it is necessary for doctors to use different codes depending on whether they communicate with each other, with their patients, or outsiders. Such codes are every day language, technical language, scientific language and language to the knowledge of different groups of non-specialists. PMID- 7871795 TI - [Truth and reality]. AB - Communication presumes the truth of statements. According to H. Weyl, the direct occurrence is subjective and absolute, the objective world relative, represented by figures and symbols, after induction of a co-ordinate system into the world. Sentences shall express relations between persons, things and properties. The message of a sentence is true, if the facts of a case prove right in reality. Thomas von Aquin: "Veritas est adaequatio rei et intellectus." To recognize a fact the reception of both "objective" signs and "subjective" forming of models are necessary. The objective and the subjective are linked strongly in the cognition. A true sentence develops if the meaning of the signs, which derive from the facts are in harmony with those, which come from the sentence by itself. Signs have to be decoded (subjectively). The attempt of making accessible the "objective" world is done with a system of rules and methods, which is without contradiction and clear in itself. Reality can be recognized only in that manner in which language can present it. "A sentence is true, if the facts of the case, which is referred by the sentence, are true." The problem, the reference of this message by itself, was solved by Tarski, inducing the term "object language" and declaring the sentences as objects of the natural (meta-)language. There are no terms as "true" or "wrong" in the object language. K. R. Popper differentiates 3 worlds: world of reality, of subjectivity, and of objectivity. Communication results from the subjective world, she rouses up emotions and reflexes. Nevertheless objectivity remains the controlling instance for messages and imaginations of the subjective ideas. The objective ideas differ from subject ones because of the possibility of associating ideas of a certain class of constellation of signals to the reality (concrete ideas), or because they can be found in a system of rules, which enables one to associate to a constellation of signals and to control this association (abstract ideas). These ideas of the "3rd world" may be regarded as supervising instances for intersubjective communication. PMID- 7871796 TI - Wisconsin's future requirements for generalist physicians: is the state's training capacity sufficient? AB - The need for expansion of generalist residency training programs in Wisconsin is considered, using population-based considerations and projection models that estimate the future statewide supply of and requirements for generalist physicians. In 1990, Wisconsin's generalist physician-to-population ratio was relatively low, at 59 per 100,000 population. The supply of generalists per 100,000 population was also highly variable across broad geographic areas of the state, with 16 of Wisconsin's 25 Health Service Areas having ratios which fell below 59 per 100,000 population. These patterns may not automatically translate into the need for expansion of Wisconsin's generalist residency training capacity, however. The projection model indicates that, even with no expansion of graduate medical education capacity for generalist physicians, the statewide supply could grow to more than 70 generalists per 100,000 population by the year 2015. Expansion of the state's generalist training capacity would also not guarantee that any additional generalist physicians trained in the state would actually locate in areas where they would be most needed. Policy efforts to provide incentives for generalist physicians to locate in under-served areas should continue to be supported. PMID- 7871797 TI - A simplified method for treating Graves' disease with radioactive 131I. AB - We reviewed the medical records of 53 patients treated in 1986 for Graves' disease with moderate doses of 131I. The cumulative incidence of hypothyroidism at 3 and 12 months after therapy was 38 and 80%, respectively. The hyperthyroidism, however, was rapidly cured and only 4(7.5%) patients required a second dose of 131I. In a separate study of 21 patients with Graves' disease, we determined that the 4-hour 123I uptake measurement was as reliable as the standard 24-hour test for supporting the diagnosis of hyperthyroidism. We also demonstrated that the 4-hour uptake accurately predicted the 24-hour uptake. Based on these findings and a review of the literature, we believe that either a 4 or 24-hour 123I uptake study followed by the administration of a fixed dose of 131I (10 or 15 mCi) provides a convenient and cost-effective method for treating Graves' disease. PMID- 7871798 TI - CESF Medical Outcomes Research Project: implementing outcomes assessment in a clinical setting. PMID- 7871799 TI - Quality improvement foundations. PMID- 7871800 TI - Creating the Medical Outcomes Research Project: an update. PMID- 7871801 TI - The SMS-CESF Medical Outcomes Research Project. PMID- 7871802 TI - Medical students health habits: do future physicians have healthy lifestyles? PMID- 7871803 TI - Summary of 1995 Medicare Part B changes. PMID- 7871804 TI - Medicine's next challenge: answering the value question. PMID- 7871805 TI - Fatty acids and lipids: biological aspects. Proceedings of the 1st International Congress of the International Society for the Study of Fatty Acids and Lipids (ISSFAL). Lugano, Switzerland, June 30-July 3, 1993. PMID- 7871806 TI - The future of fatty acids in human nutrition: health and policy implications. PMID- 7871807 TI - Intercellular communication in fatty acid metabolism. PMID- 7871809 TI - Mature milk from Israeli mothers is rich in polyunsaturated fatty acids. PMID- 7871808 TI - The influence of maternal vegetarian diet on essential fatty acid status of the newborn. PMID- 7871810 TI - Molecular species composition of plasma phosphatidylcholine in human pregnancy. PMID- 7871811 TI - Arachidonate and docosahexaenoate biosynthesis in various species and compartments in vivo. PMID- 7871812 TI - Docosahexaenoic acid supply to the retina and its conservation in photoreceptor cells by active retinal pigment epithelium-mediated recycling. PMID- 7871813 TI - The accretion of docosahexaenoic acid in the retina. PMID- 7871814 TI - Local synthesis and targeting of essential fatty acids at the cellular interface between blood and brain: a role for cerebral endothelium and astrocytes in the accretion of CNS docosahexaenoic acid. PMID- 7871815 TI - Distribution, processing and selective esterification of essential fatty acid metabolites in the fetal brain. PMID- 7871816 TI - Effect of diet on term infant cerebral cortex fatty acid composition. PMID- 7871817 TI - Modification of low density lipoprotein in relation to intake of fatty acids and antioxidants. PMID- 7871818 TI - Peroxidation of low density lipoproteins and endothelial phospholipids: effect of vitamin E and fatty acid composition. PMID- 7871819 TI - Interaction of omega 3 polyunsaturated fatty acids and vitamin E on the immune response. PMID- 7871820 TI - Effect of omega 3 fatty acids and vitamin E supplements on lipid peroxidation measured by breath ethane and pentane output: a randomized controlled trial. PMID- 7871821 TI - Physiological requirements of vitamin E as a function of the amount and type of polyunsaturated fatty acid. PMID- 7871822 TI - Trans fatty acids in early human development. PMID- 7871823 TI - Trans fatty acids: effects on eicosanoid production. PMID- 7871824 TI - An overview of the pathways for the beta-oxidation of polyunsaturated fatty acids. PMID- 7871825 TI - Effect of trans fatty acids on platelet function. PMID- 7871826 TI - Effect of trans fatty acids on serum lipoprotein levels in man. PMID- 7871827 TI - Alternatives for nutritional trans fatty acids. PMID- 7871828 TI - Inherited defects of fatty acid oxidation. PMID- 7871829 TI - The role played by beta-oxidation in unsaturated fatty acid biosynthesis. PMID- 7871830 TI - Tetradecylthioacrylic acid, a beta-oxidation metabolite of tetradecylthiopropionic acid, inhibits fatty acid activation and oxidation in rat. PMID- 7871831 TI - A new look at fatty acids as signal-transducing molecules. PMID- 7871832 TI - Health policy aspects of lipid nutrition and early development. PMID- 7871833 TI - Significance of omega 3 fatty acids for retinal and brain development of preterm and term infants. PMID- 7871834 TI - Growth and development of premature infants in relation to omega 3 and omega 6 fatty acid status. PMID- 7871835 TI - Polyunsaturated fatty acids in the developing human brain, red cells and plasma: influence of nutrition and peroxisomal disease. PMID- 7871836 TI - Beta-oxidation of hydroxyeicosatetraenoic acids: a peroxisomal process. PMID- 7871837 TI - Trans fatty acids and the human infant. PMID- 7871838 TI - Milk lipids and neonatal fat digestion: relationship between fatty acid composition, endogenous and exogenous digestive enzymes and digestion of milk fat. PMID- 7871839 TI - The ratio of linoleic acid to alpha-linolenic acid in infant formulas: current facts and future research directions. PMID- 7871840 TI - Infant feeding: antioxidant aspects. PMID- 7871841 TI - Chondrocyte allograft transplantation for damaged growth plate reconstruction. AB - The growth plate is responsible for longitudinal bone growth. The problem of repair of damaged growth plate in children has never been adequately solved. The purpose of this study is to investigate the ability of the cultured chondrocyte for the prevention of bony bridge and repairment of damaged growth plate. Chondrocytes were obtained from the new born canine epiphyseal plate and was cultured in high density. Fourteen days later they formed micromass easily removable from the culture flask. Twenty dogs were divided into two groups; in group I, the medial proximal tibial growth plate was destroyed and then cultured chondrocytes were transplanted into the defect, and in group II, the medial proximal tibial growth plate was left in destroyed state. Each left leg was remained as a control. The growth pattern was observed radiographically and histologically until 16 weeks after graft. 4 weeks after the operation, the angular deformity had been observed, and 31 degrees of angulation was noted at the 16th week in group II, while there was less than 8 degrees of angulation and nearly normal growth in most of dogs of group I (8 of 10 dogs). The other 2 dogs had shown 20 degrees angulation. In group II, there was definite bony bridge on the medical proximal growth plate. In group I, initially, the cultured chondrocyte remained as a amorphous cartilagenous mass, but as time progressed, amorphous cartilagenous mass had formed cartilagenous matrix which was proved by Safranin-O staining. Although this study showed the role of cultured chondrocyte as a method of preventation of bony bridge formation and possibility to repair of growth plate, further studies should be done to prove the reconstruction of the growth plate. PMID- 7871842 TI - The effect of deferoxamine on the preneoplastic lesions in the chemically induced hepatocarcinogenesis. AB - Iron is essential for the growth of all living cells. One of the most important intracellular roles of iron is the activation of ribonucleotide reductase, which is indispensible to the production of deoxyribonucleotide necessary for DNA synthesis. Deferoxamine (DFO) is an iron chelating agent and has been known to have an antiproliferative effect in various malignant cells including hepatocellular carcinoma and the effect seems to be related to depletion of iron. This study was undertaken to investigate the effect of DFO on preneoplastic lesions in chemically induced hepatocarcinogenesis. The resistant hepatocyte model was used and Sprague Dawley rats were divided into the following groups; I: normal control, II: carcinogen administered group, III: carcinogen and DFO administered group. Rats were sacrificed at 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks and 8 weeks after partial hepatectomy (PH). DFO (50 mg/kg/day, I.P.) was daily injected from 3 weeks before administration of carcinogen to the time when rats were sacrificed. Hepatic iron content was higher in group II than in group III, especially at 3 days and 1 week after PH. Hyperplastic lesions of resistant hepatocytes were less well developed in group III than in group II. Bromodeoxyuridine labelling indices of oval cells and hyperplastic lesions of resistant hepatocytes were higher in group II than in group III except for rats examined at 3 days after PH. The results suggest that DFO has an antiproliferative effect on preneoplastic lesions in hepatocarcinogenesis and it might be related to reduction of the hepatic iron. PMID- 7871843 TI - Transrectal ultrasonography in preoperative staging of rectal cancer. AB - A precise knowledge of the depth of invasion of tumor is essential for the planning of treatment of rectal cancer. Transrectal ultrasonography is a new diagnostic modality that has become useful in determining the depth of invasion preoperatively and the presence or absence of metastatic lymph nodes. Transrectal ultrasonography was used in preoperative staging of 36 patients with rectal cancer. Thirty three patients had a radical resection (17 low anterior resection, 15 abdominoperineal resection and 1 pelvic exenteration), one patient had a local excision. Two among these thirty four patients had preoperative radiotherapy. Preoperative transrectal ultrasonographic staging was compared with pathologic findings. In staging depth of invasion, the overall accuracy was 88.8 percent, overstaged in 5.8 percent, understaged in 5.8 percent. Transrectal ultrasonography is the more accurate method than CT in staging of depth of tumor invasion (61.8% vs 88.8%). In staging of lymph nodes, the overall accuracy of transrectal ultrasonography was 85.3 percent, sensitivity was 71.7 percent and specificity was 88.8 percent. Transrectal ultrasonography is a safe, inexpensive and accurate staging method in the assessment of both depth of invasion and nodal status. PMID- 7871844 TI - Immunohistochemical studies from vitiligo--comparison between active and inactive lesions. AB - Vitiligo is an acquired, progressive depigmenting disorder of unknown etiology. In this study, to clarify pathogenesis of vitiligo, the marginal skin of actively spreading and stable vitiligo was examined using ICAM-1, HLA-DR, CD4 and CD8 monoclonal antibodies. In immunohistochemical study, ICAM-1 was expressed in four of five epidermis in active lesions, but not in stable lesion. Dermal ICAM-1 was also expressed in all active and stable lesions. HLA-DR was also expressed in all active epidermis in active lesions, but two of five epidermis in stable lesion. Dermal HLA-DR was also expressed in all active and stable lesion. CD4 lymphocytes were expressed more strongly in active lesion, but CD8 lymphocytes were not different in both lesions. There was no significant difference of degree of positivity with CD4 and CD8 in normal control specimens. In conclusion, we think that ICAM-1 and HLA-DR expression, cytokines released from keratinocytes, melanocytes or lymphocytes and infiltration of activated T-lymphocytes play an important role in disease activity. PMID- 7871845 TI - Mechanism of decrease in heart rate by peripheral dopaminergic D2-receptors. AB - We performed this study in order to verify the heart rate decrease caused by the D2-receptor on cardiac sympathetic nerve endings and its relation to the concentration of norepinephrine in synaptic clefts. Sprague-Dawley rats were pithed and the heart rate was increased either by electrical stimulation of the cardiac accelerator nerve or by intravenous infusion of norepinephrine, tyramine, or isoproterenol. Increased heart rate by electrical stimulation of cardiac accelerator nerve was dose-dependently lowered by lisuride and its effect was blocked by pretreatment with sulpiride but not with yohimbine and SCH 23390. Also, the heart rate was decreased in a dose-dependent manner by clonidine and this effect was blocked by pretreatment with yohimbine, but not with sulpiride. For increased heart rate by infusion of norepinephrine, tyramine, or isoproterenol, the heart rate lowering effect of lisuride was more marked in the norepinephrine-and tyramine-infusion groups, in which the intrasynaptic concentration of norepinephrine was elevated, compared to the isoproterenol infusion group, in which intrasynaptic concentration of norepinephrine was not elevated. In conclusion, there is a D2-receptor on the cardiac sympathetic nerve endings which decreases the heart rate and is different from the presynaptic alpha 2-receptor. Also, the heart rate lowering effect via stimulation of the D2 receptor by lisuride was more marked with increased concentration of norepinephrine in the synaptic cleft. PMID- 7871846 TI - Determinations of personal carbon monoxide exposure and blood carboxyhemoglobin levels in Korea. AB - Determinant factors for personal carbon monoxide (CO) exposures were sought in Korea, where CO poisoning has been a major public health problem due to coal briquette (Yeontan) combustion for space heating and cooking. Personal 24-hr CO exposures of 15 housewives were measured by CO passive samplers on 2 days of the week (Wednesday and Sunday). Blood samples were taken to measure carboxyhemoglobin (COHb) just after the exposure sampling. Average CO exposure and COHb level were 5.6 ppm and 2.4%, respectively. Personal CO exposures as well as COHb levels were significantly increased by the use of Yeontan, especially on a weekday. Carboxyhemoglobin levels were closely related to the time between blood collection and replacement of Yeontan: the closer the blood collection was to replace Yeontan, the higher the COHb levels were. Assuming a background COHb of 1.34%, COHb increased on average by 1.8% with a 24-hr personal CO exposure of 10 ppm. The relationship between CO exposure and COHb level was provided by simultaneous direct measurements in real environment, although a measurement of COHb at the end of exposure could not represent previous 24-hr exposure thoroughly. PMID- 7871847 TI - Comparison of sympathetic skin response and digital infrared thermographic imaging in peripheral neuropathy. AB - It is well known that the SSR (sympathetic skin response) is to evaluate the function of sudomotor activity and Digital infrared thermal imaging (DITI) is to evaluate the function of vasomotor activity of the sympathetic nerve. To assess the sympathetic nerve impairment in the patients with peripheral neuropathy, the SSRs and DITIs were tested in 35 cases. Twenty-four (68.6%) patients were abnormal on SSR test and twenty-nine (82.9%) patients were abnormal on DITI test. In the relationship between DITI and SSR, 19 (54.3%) cases were abnormal and 1 case was normal finding in both of these two tests. And the remaining 25 (42.9%) patients were abnormal on only either one of both tests. Frequency of abnormal SSR and DITI findings were correlated with severity of axonal involvement in peripheral nerve lesion. The results of this study revealed DITI to be more sensitive test in assessing sympathetic dysfunction in peripheral neuropathy than the SSR. However DITI has very limited values in the patients with symmetrically involved peripheral neuropathy because thermal asymmetry is considered as abnormal on DITI. Therefore, in assessing the function of sympathetic nerve in peripheral neuropathy, combined tests of SSR and DITI are useful. PMID- 7871848 TI - Significance of Langerhans' cells in middle ear cholesteatoma. AB - Recent advances in immunology have opened a new approach to investigating the etiology and pathogenesis of aural cholesteatoma by the immunohistochemical technique. Immunohistochemical and submicroscopic analysis of human cholesteatoma matrices revealed the presence of Langerhans' cells. Several reports have suggested that Langerhans' cells in cholesteatoma are significant, and that the pathogenesis of this disease including bone resorption could be explained as a cell-mediated immune response, but this is still controversial. In this study, Langerhans' cells in cholesteatoma were quantitated and compared with those in postauricular skin and in skin of the open mastoidectomized cavity. The results did not support the hypothesis that Langerhans' cells have a primary role in the development of aural cholesteatoma. PMID- 7871849 TI - Mid-sagittal canal diameter and vertebral body/canal ratio of the cervical spine in Koreans. AB - In order to ascertain the normal values of the mid-sagittal canal diameter and the canal/body ratio of the cervical spine in Korean adults, ninety sets of cervical vertebral columns were examined. The average mid-sagittal canal diameters from C3 through C7 in the normal Korean are 13.2 +/- 1.3 millimeters in male and 13.1 +/- 2.6 millimeters in female. The normal average canal/body ratio of the cervical spine is 0.93 +/- 0.10 in male and 1.02 +/- 0.09 in female. The mid-sagittal canal diameter is largest in the White population and smallest in Asian, but there is no racial differences in the canal/body ratio, and the lower limit of normal canal/body ratio is 0.8 in Korean. The authors conclude that measurement of the canal/body ratio is more reliable than direct measuring of the mid-sagittal diameter of the cervical spinal canal in the diagnosis of cervical spinal stenosis or predicting the prognosis of cervical spinal cord injury. PMID- 7871850 TI - Measurement of IgE and IgG subclass antibodies to whole body antigen and two major allergens (Der fI & Der fII) of Dermatophagoides farinae in normal subjects and asthmatics. AB - House dust mites have been known as the most important allergen in respiratory allergic diseases. Among several mite allergens, group I and group II antigens were recognized as major allergens. We measured specific IgE and IgG subclass antibodies against whole body antigen (WBA) and two major allergens of Dermatophagoides farinae (Der fI and Der fII) in sera from 66 adults with asthma (asthma group) and 34 normal subjects (healthy group) by ELISA. The mean O.D. values of WBA-specific IgE and IgG subclass antibodies in 100 studied sera were significantly higher than those of the two major allergens (p < 0.001) and the level of Der fII- IgG1, IgG4 and IgE were higher than those of Der fI but IgG2 of Der fI was higher than that of Der fII (p < 0.001). The level of IgG4 of WBA were significantly higher in the atopic group than in the nonatopic group (1.280 +/- 0.634 v.s. 0.8290 +/- 0.388, p < 0.001), but the WBA- IgG1, IgG2, IgG3 were not different between the two groups. Among IgG subclass antibodies of Der fI, IgG2 was significantly higher in the nonatopic group than in the atopic group (1.7770 +/- 0.255 v.s. 1.636 +/- 0.390, p < 0.05) but there were no differences in IgG1, IgG3, and IgG4. Among IgG subclass antibodies of Der fII, IgG2 (1.534 +/- 0.380 v.s. 1.3010 +/- .431, p < 0.05) and IgG4 (1.09650 +/- .567 v.s. 0.708 +/- 0.146, p < 0.001) were significantly higher in the atopic group than in the nonatopic group. IgE antibodies to WBA, Der fI and Der fII were significantly higher in the atopic group (p < 0.001). There were significant correlationships between the levels of IgE and IgG4 of WBA (r = 0.60), Der fI (r = 0.33) and Der fII (r = 0.72). Even though there were no differences in the levels of allergen specific IgE and IgG subclass antibodies between nonatopic healthy and nonatopic asthmatic groups, the number of sera with prominent level of IgG2 of WBA were more common in the nonatopic asthmatic group (69% in nonatopic asthma group v.s. 28% in nonatopic healthy group, X2-test, p < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7871851 TI - The basal electrical skin resistance of acupuncture points in normal subjects. AB - The inhibitory component of the skin against given electrical current, also called as the electrical skin resistance, is subject to change in response to many factors, especially pain. In order to find out more definite relationship between pain and skin resistance, one should make measurement in the state devoid of any external disturbing stimuli to get the "basal skin resistance (BSR)", which is known to be different from point to point on body surface. Also, the "active points" have more consistent BSR characters than other points and most of them share same locations with "acupuncture points" which is easy to localize accurately and repeatedly in normal subject. Therefore, the comparison of BSR of certain acupuncture points of normal subject and pain-suffering subjects is expected to be able to figure out any pain-induced BSR changes. Our measurement at 16 acupuncture points (asymmetrical 8 pairs) of 10 normal subjects showed inconsistently asymmetrical distribution of the BSR values with significant order among themselves including left SP (spleen)-6 at their lowest position, but neither the measuring system itself nor any of the 16 points was statistically reliable enough for diagnostic purposes. So the measuring device needs to be improved with after evolution, and more acupuncture points need to be explored to complete our pain-related BSR map. In addition, the meaning of the above BSR distribution pattern is waiting to be explained through such efforts. PMID- 7871852 TI - Three dimensional structures of pulmonary elastin; airway vs vascular elastin. AB - Elastin is known to occur in the lung parenchyma and pleura as well as in the pulmonary vessels, but no detailed studies of this elastin's linkage between them have been done in three dimensions. For many years we have known that there is abundant elastin in the mammalian lungs, which may be associated with etiology of causing emphysema. We have developed selective casting methods to allow us to determine the location where elastin is found morphologically. The method involves casting either the vasculature via the right ventricle, or the airways via the trachea in the air sacs. Studies of the vasculature were done with the lung inflated to 80% of the vital capacity. The casted lungs were then put in 0.1 N NaOH at 75 degrees C for 48 hours, turning them frequently. THis method removed all non-elastin tissues. The scanning electron microscopy (SEM) was used to reveal the three dimensional pictures of elastin structures from both lung parenchyma and pulmonary vessels. Elastin was seen as fenestrated sheets and some fibers in both the vessels and the airways. Elastin in the two different locations was often interconnected. Studies on 6 dogs, 8 rabbits, and 2 pigs showed no significant species difference at the level of resolution of the SEM, which was used to study the specimens after they had been freeze-dried. PMID- 7871853 TI - Endothelial F-actin changes in the alkali burned rabbit cornea. AB - The healing mechanism of corneal endothelium after alkali burn was not completely understood. Rabbit cornea was burned with 1N sodium hydxoside for 1 minute. Endothelial F-actin was stained with NBD-phallacidin in regular sequence to find out the details of endothelial healing after alkali burn. F-actin was completely destroyed leaving a sharp margin against the unaffected area 1 hour after the burn. In the 3, 5 and 7 day specimens, highly active F-actin reactions were noted at the wound margin. New multiple F-actin layers, arising from the intact endothelium near the wound margin, were noted in the 9 day specimen. In the 8 1/2 month specimen, the endothelial defected area was covered by large primitive cells, each of which showed F-actin fiber bundles in the cytoplasm with a large nuclear shadow. Nearly all of the large primitive cells showed F-actin fibers arranged in shapes of cell junctions. Twelve months after the burn, endothelial defects were not found. Nearly all of the endothelial cells were normal in size and shape except for some mushroom-like projections toward the anterior chamber in some areas. Nineteen months after the burn, the endothelial cells were normal. Endothelial wound healing process can be continued even 1 year after the alkali burn in rabbit cornea. PMID- 7871854 TI - Effect of adenylate cyclase inhibitor and protein kinase C inhibitor on GnRH induced LH release and LH beta subunit biosynthesis in rat anterior pituitary cells. AB - According to our previous studies together with others, GnRH, a hypothalamic decapeptide, has been known to be a major regulator for LH release and its subunit biosynthesis in anterior pituitary gonadotropes. But the precise mechanisms by which GnRH exerts stimulatory effects on LH release and its subunit biosynthesis have not been clearly understood. In the present study we examined the effect of GnRH on protein kinase C (PKC) activity and intracellular cAMP content in cultured anterior pituitary cells of rat to clarify whether PKC or cAMP are involved in GnRH action. Moreover, we examined the effects of staurosporine (ST), a PKC inhibitor and 2',3'-dideoxyadenosine (2',3'-DDA), an adenylate cyclase inhibitor, on LH release and steady state LH beta subunit mRNA levels in cultured anterior pituitary cells of rat. PKC activity was rapidly increased within 30 min after GnRH treatment whereas intracellular cAMP level was elevated 18 h after GnRH treatment. ST significantly inhibited GnRH-induced LH release and LH beta subunit mRNA levels in a dose-dependent manner, showing an half maximal response at 50 nM ST. 2',3'-DDA inhibited GnRH-induced LH release and LH beta subunit mRNA levels in a dose-dependent manner in pituitary cells. From these results, it is suggested that GnRH stimulates LH beta subunit mRNA level as well as LH release in anterior pituitary cells and this GnRH action might be mediated by PKC activation and cAMP stimulation. PMID- 7871855 TI - Liposome mediated in vivo gene transfer into different tissues of the gastrointestinal tract. AB - The possibility to transfer and express genetic material in mammalian cells represents a new approach to the treatment of genetic and acquired disorders. So far, most studies use in vitro techniques to introduce foreign DNA into cultured cells, followed by reintroduction of these genetically altered cells into living organisms. In the present study we demonstrate that the LacZ marker gene can be selectively delivered, by in vivo techniques, to various locations of the gastrointestinal tract. Genetic material was targeted to the stomach, the colon, the liver and the pancreas using cationic liposomes. For transfer into the stomach and colon an intraluminal application, in the liver a portal access and in the pancreas an intraductal infusion was chosen. 48 hours after administration, the LacZ gene product beta-galactosidase could be localized in these tissues by cytochemistry. These experiments suggest a new approach to study gastrointestinal physiology and may offer novel aspects for the treatment of gastrointestinal diseases. PMID- 7871856 TI - [Radiation burden in diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP)]. AB - The increasing expansion of diagnostic and, in particular, of therapeutic ERCP calls for greater consideration of the radiation dose to which the investigator and assistant personal are exposed and emphasizes the question of additional radiation protection measures such as leadshielded glasses and thyroid protection. MATERIALS AND METHODS: Local radiation doses were measured in 19 ERCP sessions at head level of the endoscopist, assistant staff and the radiologist, respectively. The fluoroscopic time, the area dose product (ADP) and the measuring height were recorded. A quotient based on the measured local dose and the ADP was formed which includes all variables having an effect on the scattered radiation. Using this quotient and the known ADP-values radiation exposure levels were mapped over a period of three months and then extrapolated to obtain the annual dose. RESULTS: Not only the FT, but also the ADP, the measuring height, and the source-image-distance (SID) are found to influence the magnitude of the radiation dose to which the investigator and his assistants are exposed at head level. For an assumed rate of 1200 ERCPs per year a median radiation at head level of 16.5 mSv/a is calculated for the investigator, and a corresponding head level dose of 5.5 mSv/a for the assistants. This shows that the eye dose to which the investigator (and his assistants) are exposed amounts to 10% (5%) and the thyroid dose to 5% (1.5%) of the legally prescribed limit dose. If fewer ERCPs are performed, or if the investigations are divided up among several doctors and assistants, radiation exposure is reduced accordingly. CONCLUSIONS: Under the prevailing investigation conditions additional radiation protection measures such as leadshielded safety glasses or thyroid protection do not appear necessary. PMID- 7871857 TI - Clinically feasible stable isotope technique at a reasonable price: analysis of 13CO2/12CO2-abundance in breath samples with a new isotope selective nondispersive infrared spectrometer. AB - Up to now, stable isotope analysis of carbon dioxide in breath samples is carried out with sensitive but very expensive and complex isotope ratio mass spectrometry (IRMS). Aiming at a more widespread application of breath tests in gastroenterological diagnostic routine, we tested a newly developed isotope selective non-dispersive infrared spectrometer (NDIRS) in comparison to IRMS. 13C urea breath tests were performed in 63 patients as the routine screening method for Helicobacter pylori infection. Breath samples at baseline and (15) 30 min after administration of the test solution containing 13C-urea were analysed both by NDIRS and conventional IRMS. The correlation between the delta values of both devices was linear and in good agreement (r = 0.96; p < 0.0001; Y = 1.01 X 0.94). Comparing the delta over baseline-values, the correlation was Y = 1.11 X 0.36 (r = 0.98; p < 0.0001). Referring to the diagnosis of Helicobacter pylori infection with IRMS we calculated a sensitivity of 95.0% and an unchanged specificity (100%) for NDIR analysis. In conclusion, NDIRS appears a promising, easy to operate, and low cost potential alternative to conventional IRMS thus encouraging further detailed investigation and more widespread application of the noninvasive stable isotope technique in breath tests for gastrointestinal function testing. PMID- 7871858 TI - Lack of accuracy of plasma alpha-amino nitrogen profiles as an indicator of exocrine pancreatic function both after continuous and bolus stimulation of the pancreas with secretin and cholecystokinin-pancreozymin. AB - BACKGROUND: The reduced decrease of plasma alpha-amino nitrogen after hormonal stimulation of the pancreas has been characterized as a valid and simple test of pancreatic function. Aim of this study was to reassess the clinical value of the alpha-amino nitrogen test and to evaluate the role of different modes of hormonal secretion. Therefore, we have investigated the relationship of plasma alpha-amino nitrogen responses and pancreatic secretion, stimulated by either bolus injection (n = 25) or continuous infusion (n = 32) of cholecystokinin-pancreozymin in patients with and without exocrine pancreatic insufficiency as determined by the secretin-pancreozymin test. Of the 57 patients referred to the secretin pancreozymin-test, 18 had pancreatic insufficiency, each 9 in the group with continuous and bolus stimulation. RESULTS: Basal alpha-amino nitrogen concentrations were almost identical in patients with and without impaired pancreatic function (2.66 +/- 0.12 mmol/l vs. 2.73 +/- 0.08 mmol/l [SEM]; p > 0.05). Both, the bolus dose and infusion of cholecystokinin induced similar (log normally distributed) maximum decreases of alpha-amino nitrogen concentrations ( SD; mean; + SD: 3.6; 9.0; 22.3% vs. 6.0; 10.5; 18.5%, respectively) in the patients without exocrine pancreatic insufficiency. This was in tendency more pronounced compared to those with impaired pancreatic secretion (cholecystokinin bolus; 2.7; 5.2; 9.9%; infusion: 5.0; 7.7; 11.6%). The difference (+/- exocrine pancreatic insufficiency) was significant (p < 0.05) for the infusion mode only. Moreover, the time course of alpha-amino nitrogen concentration-profiles was more homogenous after hormone infusion as compared to bolus stimulation. Sensitivities to detect exocrine pancreatic insufficiency by the alpha-amino nitrogen test were < 50% with either test modification. CONCLUSION: The decrease of plasma alpha amino nitrogen after stimulation with cholecystokinin is no accurate indicator of exocrine pancreatic function, regardless of whether hormonal stimulation is by bolus or by infusion. PMID- 7871859 TI - [Low malignancy MALT lymphoma of the stomach: H. pyloric eradication as a therapeutic concept?]. AB - A 63 year old patient came to admission because of abdominal pain. A stone disease of the gallbladder was known. Gastroscopy showed active gastritis of the antral-mucosa with some erosive lesions. Histology revealed surprisingly a low grade MALT lymphoma. Helicobacter pylori colonization (H. pylori) was found in the mucosa. While additional lymphomas were not found, a therapy aiming at the eradication of H. pylori was started. A subsequent control biopsy showed only slight lymphoplasmacellular inflammatory infiltration of the mucosa but no evidence of lymphoma. Our case report shows, that regression of a gastric MALT lymphoma can be achieved by eradication of H. pylori only. So far we don't know for how long this regression will continue and if permanent healing is possible. Further studies will have to show whether eradication of H. pylori can be established as a new therapeutic concept of low-grade MALT lymphomas at early stages. PMID- 7871860 TI - Successful monochemotherapy of extensive gastrointestinal Kaposi's sarcoma with bowel obstruction in acquired immunodeficiency syndrome. AB - We report the case history of a 28-year-old homosexual man of Caucasian origin whose diagnosis of acquired immunodeficiency syndrome was established one year before admission on the basis of a positive human immunodeficiency virus serology and cutaneous Kaposi's sarcoma. Severe postprandial vomiting pointed to bowel obstruction in an emaciated, poor risk patient. Endoscopy revealed multifocal, violaceous tumours throughout the upper gastrointestinal tract which, eventually, obstructed the duodenum. Histology confirmed the putative diagnosis of gastrointestinal Kaposi's sarcoma, which responded well to monochemotherapy with vincristine. Significant clinical improvement and repeat endoscopy indicated tumour regression and resolution of bowel obstruction. PMID- 7871861 TI - [The significance of cytokines and extracellular matrix for stomach ulcer healing]. AB - The healing process of gastric ulcers is regulated by many factors. Cytokines play a central role in the different stages of healing. In the early stage of inflammation, TNF-alpha and interleukins regulate cell-migration and proliferation. In the ulcer's base revascularisation is stimulated by b-FGF, collagen synthesis by TGF-beta. The reepithelialization is mediated by EGF, which accelerates ulcer healing in animal models, while TGF-alpha is involved in mucosal protection. The extracellular matrix (ECM) is important for the stability and quality of the ulcer scar, as known from dermatological experiments. An increase of collagen types I and III in healing gastric ulcers was demonstrated recently, which might illuminate the particular role of ECM proteins for the gastric ulcer healing process. PMID- 7871862 TI - [Diagnostic and therapeutic possibilities in suspected Oddi's sphincter dysfunction]. AB - Endoscopic manometry and quantitative cholescintigraphy are the diagnostic cornerstones for the detection of suspected sphincter of Oddi dysfunction. In patients with recurrent biliary pain after cholecystectomy, endoscopic manometry proves an elevated sphincter of Oddi baseline pressure as the most common finding. The probability for the detection of an elevated baseline pressure in these patients is significantly correlated with the presence of certain clinical features (i.e. biliary pain and/or cholestasis and/or dilated bile duct and/or delayed drainage of contrast material after ERCP). Therefore, these features enable a clinical classification of patients with suspected sphincter of Oddi dysfunction. Isolated baseline pressure elevations in the pancreatic portion of the sphincter of Oddi were reported in patients with recurrent, idiopathic, acute pancreatitis. In patients with biliary sphincter dysfunction, therapeutic relief can be expected from pharmacological therapy, but controlled studies are lacking. However, the clinical value of endoscopic sphincterotomy could be established in this field. Despite endoscopic manometry is not a prerequisite for the performance fo endoscopic sphincterotomy in every case of suspected sphincter of Oddi dysfunction, in most patients endoscopic manometry allows the only definitive diagnosis of sphincter dysfunction. Further on, the clinical value of semi-invasive methods as alternative treatment strategies (i.e. botulinum-toxin, transcutaneous electric nerve stimulation, balloon dilation) for sphincter of Oddi dysfunction has to be evaluated in the future. PMID- 7871863 TI - [Transjugular intrahepatic portosystemic stent shunt in bleeding esophageal varices]. PMID- 7871864 TI - [The amino acid absorption test is not a suitable test for diagnosis of exocrine pancreatic insufficiency]. PMID- 7871865 TI - [Applications of endoscopy in esophageal diseases. German Society of Digestive and Metabolic Diseases]. PMID- 7871866 TI - [Ecologic gerontology: more than the docility hypothesis?]. PMID- 7871867 TI - [The importance of the home for healthy and disabled elderly persons]. AB - The majority of old people live in private households and they want to remain there. Starting from this insight, the study is focused on the interaction between older people and their home environment. Some theoretical assumptions on the role of housing are presented, namely the competence theory perspective, the continuity theory perspective, the perspective of research on leisure time and everyday life activities, the environmental adaptation perspective, and the environmental gerontology perspective. Previous research has shown that there is a strong correlation between environmental-relevant competence loss (e.g., mobility impairment) and objective living arrangements. Little attention has been paid, however, to the subjective meaning of home in old age (e.g., processes like familiarity or stimulation), either with or without competence loss. This paper presents preliminary results of an investigation into that "Aging in Place" issue, based on semi-structured interviews with 84 participants between the age of 62-92 (M = 77 years). Forty-two subjects were in good health status, 42 suffered from severe mobility impairments. The participants were visited at home and all interviews were tape-recorded. On one hand, the general meaning of home, on the other, specific sections of the home environment were analyzed (most favorite place within the home, favorite meaningful things). The results revealed that the two groups of participants are similar as far as the general meaning of home is concerned. In the experience of the most favorite place at home, subjects suffering from mobility impairments are tending more to an environmental "centralization" than healthy subjects do. With respect to personal objects, the most often mentioned meaning was "reminiscence". By and large, the results of this work support the view that knowledge about the meaning of home can be of help to better understand how old people create their meaningful everyday life at home and why they want to "stay put"; in addition, the results can be used in planning living arrangements for people of all ages. PMID- 7871868 TI - [Assisted living: possibilities, limits and architectural requirements- considerations from the viewpoint of an architect with ecopsychological orientation]. AB - In Germany, existing experiences with "sheltered housing" are not sufficient in order to precisely define the role of this new type of housing the aged within the overall network of care for the elderly. First, this article provides an overview of how different the needs for help in old age can be, and which types of supportive environments and services fit to different situations. In this context the potential and the limits of the "sheltered home" concept are described. Second, based on some policy considerations, a program of seven design directives for the planning of sheltered homes is proposed that integrates selected theoretical approaches of environmental psychology and geropsychology. As an example for the implementation of some of the design directives, the floor plan of a recent project is described. Finally, the resistance of architects to a design, which is also based on psychological considerations is discussed. It is argued that the architects' philosophy about the fit between architecture and users' needs has a certain similarity to the "complementary-similarity-model," developed by Carp and Carp (1984). PMID- 7871869 TI - [Suitable housing--experiences of counseling facilities in Austria and Germany]. AB - The article describes the experiences made by Austrian and German counseling agencies dealing with housing adaptation with technical appliances for elderly people. The collected data from a questioning of counseling institutions, most of them still pilot projects, are assessed and special focus is given to the organization and institutionalization of the counseling agencies, to the access to the institutions, to the process and program of counseling, to obstacles and hindrances, to the costs and financing of the institutions or the adaptations. PMID- 7871870 TI - [Forms of independence and the residential environment--an empirical contribution from the study "Possibilities and limits of independent living for elderly patients"]. AB - In a study on the chances and limits of independent living in old age, we collected data about difficulties in 23 activities of daily living in two sub samples: participants from the western part of Germany (n = 745), and from the eastern part of Germany (n = 347). Participants were grouped into three patterns of competence by means of cluster analysis. Cluster analyses were calculated separately for participants in the western and eastern parts of Germany. In both sub-samples, we found three patterns of competence: "High competence in most activities of daily living", "reduced competence in some activities of daily living" and "reduced competence in most activities of daily living". Patterns of competence were similar in the sub-samples, but important differences were found in some activities of daily living between participants from the eastern and western parts of Germany (e.g., in "heating home," "washing clothes," "banking"). These differences were due to unfavorable conditions in physical environment. Analysis of the relationship between objective housing conditions (assessed by our research team) and patterns of competence strongly supported this interpretation. Participants in the two sub-samples were more satisfied with their housing conditions as could be expected from our assessment of housing conditions. Successful adaptation to environmental conditions and changes in the aspiration-level can explain these differences. The degree of satisfaction with housing conditions is only a poor predictor for possibilities in increasing competence by intervention and rehabilitation. Most participants wished to keep their household independently as long as possible. Acceptance for homes for the elderly was low. PMID- 7871871 TI - [Seeing in the dark: limited vision in the aged as a prototypical "environmentally relevant" loss in competence]. AB - In the conceptual part of this article, the existential dimension of experiencing a dramatic visual loss in late life is highlighted. Three theoretical avenues are proposed to approach age-related vision loss: 1) a stress and burden perspective; 2) a coping perspective, 3) an environmental psychology perspective. The empirical study is based on 84 elderly subjects suffering from vision loss (42 visually impaired, 42 blind), a comparison group of 42 subjects with mobility impairments, and a control group of 42 healthy subjects (particularly not impaired in vision or mobility). In all impaired groups, the impairment appeared after the age of 55 years; identification of subjects was based on medical expertise. Mean age varies between groups from 75 to 78 years with 30 females and 12 males in each group. Data based on person (e.g., ADL-functioning, subjective well-being, depressivity) as well as person-environment-transaction measures (e.g., microecology within the house, action range outside the house) were collected. Results revealed a reduced ADL-competence, lower subjective well being, higher depressivity, and a shrinkage of action range in subjects suffering from visual loss. However, there was also a need for a differential perspective: For example, depending on person variables (living alone/not alone, degree of visual loss, coping style, coexisting illnesses), a different "resilience" against environmental pressure was observed. These findings point to the importance of a "differential" environmental gerontology. PMID- 7871872 TI - [Residential mobility in the elderly. Current results of geographic mobility research in unified Germany]. AB - Elderly migrations are often considered as amenity-oriented long distance moves or as decisions for a change by moving into homes for the aged. The intention of this contribution is to prove the validity of these assumptions in the light of actual results of migration research in unified Germany. The findings of the spatial pattern of internal migrations as well as the characteristics of the migrants and their reasons underline the necessity of more differentiated considerations. They neither prove the relationships between migration participation and the available personal resources, nor the assumption that elderly migrants usually prefer long distance moves to attractive regions. Due to this, the relocations into institutions or retirement areas together only represent about one third of all migrations. The majority leaves their community and migrates to kin-oriented networks when they feel they are not able to manage their living conditions by themselves. Beside this exogenous reasons within the housing environments or the housing demands of the ethnic germans from eastern Europe force elderly to decide to move. PMID- 7871873 TI - [Aging in a foreign environment]. AB - This article discusses some aspects in Environmental Gerontology concerning the living conditions of elderly foreigners (migrants) who have been living and working in Germany for 20 to 30 years. First, deficits of the present research situation of elderly migrants are described. Second, with regard to the differentiation of "normal aging" and "aging with significant competence losses" two environment-relevant issues are analyzed: Living arrangement (home, residential unit, residential quarter) and the utilization of social services and institutions for the aged. The paper closes with some ideas on "ethnic aging and gerontological research". PMID- 7871874 TI - [Dental care in Hessian nursing homes for the aged. I: Management from the viewpoint of home administrators]. AB - All directors of all nursing homes in the German state of Hessen were interviewed about dental care and treatment of their senior inhabitants. They were also asked for some critical remarks about their staff's education concerning both oral health and hygiene. The response-rate of almost 46% shows the proband interest in this topic. The results of the opinion poll recommended further co-operation between geriatrics and gerodontics. PMID- 7871875 TI - [Dental care in Hessian nursing homes for the aged. II: Oral hygiene awareness of inmates]. AB - 325 inhabitants of several Hessian rest and nursing homes--of an average age of 81 years--have been viewed about their laymen's knowledge of dentistry, their daily oral hygiene, and their opinion about dental treatment. The majority of those senior probands did not realize any connection between insufficient oral hygiene and the origin of both caries and periodontal disease. They considered oral hygiene to be a matter of bodycare, not of medical prevention. PMID- 7871876 TI - [Functional assessment of elderly patients in a general practice]. AB - To evaluate functional disabilities in elderly patients, geriatric assessment was performed in one general practice. Excluded from the study were patients with severe dementia and dependence. 178 patients were asked to participate and 144 accepted (mean age 78.7 +/- 5.8 years; number of diagnoses 5.2 +/- 2.6; f = 95, m = 49). Mini-mental-status examination showed moderately but significantly lower (p < 0.05) cognitive capacity in the age groups of 80-84 years (n = 37, 24.56 +/- 4.90 points) and of 85 years and older (n = 30, 25.14 +/- 3.11 points), but not in the group of 75-79 years (n = 46, 26.70 +/- 3.90 points) compared to the group of 70-74 years (n = 31, 27.65 +/- 2.59 points). Neither the Geriatric Depression Scale nor the Barthel-Index (activities of daily living) showed significant differences between the age groups. The score of the instrumental activities of daily living (Lawton Index) was significantly lower (p < 0.05) in the age group 85 years and older (4.1 +/- 2.5 points) compared to the age group of 70-74 years (6.1 +/- 2.4 points). Grip strength was significantly reduced (p < 0.01) in the age group 85 years and older as well as motility and balance scores (Tinetti test; p < 0.05) compared to the group of 70-74 years (43.21 +/- 16.27 kp and 64.87 +/- 19.81 kp, resp., 19.3 +/- 6.6 and 23.1 +/- 5.9 points). No correlation was found between the results of functional assessment and number of contacts with the general practitioner in the past year, number of prescribed drugs and number of diagnoses except for the depression test. There was a significant correlation between test score, number of contacts, and number of diagnoses (p < 0.05). Functional assessment resulted in new diagnoses of urinary incontinence in 7 patients and of mobility disorders in 17 patients. Cognitive impairment was suspected in 14 patients, depression in 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871877 TI - [Determinants of nursing home admission of elderly patients and chances for prevention. A longitudinal study in Germany]. AB - The aim of the following longitudinal study of institutionalization was 1) to ascertain the risk of institutionalization of an elderly person, and 2) to examine the factors related to institutionalization in old age. The probability of an old person to spend some portion of his life in any home for the aged is much higher than the 5% (Western Germany) or the 8% (Eastern Germany) which can be observed at any point in time. In the individual life-course up to 43% of men and up to 70% of women become institutionalized. The factors related to institutionalization are age, sickness, housing conditions, and marital status, whereas the gender difference is explained entirely by other factors. Furthermore, the probability to become institutionalized in old age is also a function of mortality. PMID- 7871878 TI - [Extended family, immediate family and caregiver contacts of 100-year-old patients in Hungary]. AB - In the year 1987, 218 centenarians lived in Hungary. First the main demographic data were reported by the surveyors of the Central Statistics Office. The basis of the experience was gained on a limited population (123 subjects). The physicians' team was organized by the Gerontology Center of the Semmelweis University of Medicine. They carried out the detailed medical and environmental check-up. The medical and environmental experiences of the gerontologists were published (1). In our present paper we would like to show the different familial and other relationships of the oldest people. The 123 centenarians were scattered over the whole country, altogether in 67 larger or smaller settlements. More of them lived with a daughter (42%), with a son (14%), with a grandchild (7%), with other relatives (5%) and 3 persons lived together with their wives. We found that the subjects who lived with relatives had a better chance to live an active and meaningful life. The co-existence of several generations, the multilateral contacts of centenarians have a beneficial effect on the quality of life. PMID- 7871879 TI - [Demography of aging in Spain]. AB - In this article, the demography of the elderly in Spain is scrutinized. The older population from 1960 to 1991 and their presumed development for the period from 2001-2020 is analyzed. According to these data, we attempt to determine the influence on life situation of older people according to several factors, such as changes of family structures and intergenerational relations as well as changes in social stereotypes, expected political and economical developments, and new concepts in medical care. In closing, we raise questions about the necessary future living structures in Spain. PMID- 7871880 TI - Transcript map of two regions from chromosome XI of Saccharomyces cerevisiae for interpretation of systematic sequencing results. AB - A detailed and systematic transcript map is a first and necessary step to characterize new genes revealed by systematic sequencing. Chromosome XI of Saccharomyces cerevisiae contains 331 open reading frames (ORFs) of which 44% are of unknown function (Dujon et al., 1994). As a first study towards complete transcript analysis of chromosome XI, we have extracted RNA from three isogenic strains (a, alpha and 2n) grown in three standard laboratory media, and have analysed them using contiguous probes covering two regions of 17 and 19 kilobases, respectively. All 20 predicted ORFs in the sequences correspond to expressed genes, six of which have no predicted function. Four short ORFs which were suspected as not being real genes on the basis of their sequence are not expressed in our growth conditions. An additional transcript which does not correspond to a large ORF was found. Steady-state RNA level of most ORFs is 10 to 100 times than that of the actin gene, only three are transcribed in comparable amounts. Three ORFs show variable levels of transcripts in the different growth conditions, all patterns being different from one another. Extrapolation of these results to systematic transcript analysis of chromosome XI and other yeast chromosomes is presented. PMID- 7871881 TI - Characterization of lipid particles of the yeast, Saccharomyces cerevisiae. AB - Lipid particles of the yeast, Saccharomyces cerevisiae, were isolated to high purity and their components were analysed. The hydrophobic core of this organelle consists of triacylglycerols and steryl esters, which are almost exclusively located to that compartment. Lipid particles are stabilized by a surface membrane consisting of phospholipids and proteins. Electron microscopy confirmed the purity of the preparations and the proposed structure deduced from biochemical experiments. Major proteins of lipid particles have molecular weights of 72, 52, 43 and 34 kDa, respectively. The 43 kDa protein reacts with an antiserum against human apolipoprotein AII. In lipid particles of the yeast mutant strain S. cerevisiae erg6, which is deficient in sterol delta 24-methyltransferase, this protein is missing thereby identifying the protein and confirming our previous finding (Zinser et al., 1993) that sterol delta 24-methylation is associated with lipid particles. A possible involvement of surface proteins of lipid particles in the interaction with other organelles is discussed with respect to sterol translocation in yeast. PMID- 7871882 TI - Generation of glycerophospholipid molecular species in the yeast Saccharomyces cerevisiae. Fatty acid pattern of phospholipid classes and selective acyl turnover at sn-1 and sn-2 positions. AB - Acyl chains linked to phospholipids of the yeast, Saccharomyces cerevisiae, are mainly C16:1 and C18:1 accompanied by minor amounts of C14:0, C16:0 and C18:0. In view of this rather simple fatty acid composition, the question arose whether in yeast, as in higher eukaryotes, fatty acyl groups were characteristically distributed among the sn-1 and sn-2 positions of distinct phospholipid classes. Analysis of fatty acids linked to the sn-1 and sn-2 positions of the major phospholipids showed that indeed saturated fatty acyl groups predominated in the sn-1 positions. While the percentage of saturated fatty acids was low (10%) in phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) from cells grown on rich medium, it was higher in phosphatidylserine (PtdSer) (25%) and highest in phosphatidylinositol (PtdIns) (41%). Oleate was mainly linked to position sn-2, while palmitoleate predominated in position sn-1. Striking differences in the fatty acid distribution of phospholipids that are metabolically closely related (e.g. PtdSer and PtdEtn, PtdEtn and PtdCho, and PtdIns and PtdSer) suggest that pathways must exist for the generation of distinct phospholipid molecular species within the different phospholipid classes. The highly selective incorporation of exogenous [14C]palmitic acid (90%) and [3H]oleic acid (99%) into the sn-2 position of PtdCho, and the preferential incorporation of these fatty acids into the sn-2 position of PtdEtn (70 and 90%, respectively, for palmitic and oleic acid) are compatible with the postulate that phospholipase A2-mediated deacylation followed by reacylation of the lysophospholipids is involved in the generation of phospholipid species in yeast. PMID- 7871883 TI - The in vivo activation of Saccharomyces cerevisiae plasma membrane H(+)-ATPase by ethanol depends on the expression of the PMA1 gene, but not of the PMA2 gene. AB - The expression of the PMA1 and PMA2 genes during Saccharomyces cerevisiae growth in medium with glucose plus increasing concentrations of ethanol was monitored by using PMA1-lacZ and PMA2-lacZ fusions and Northern blot hybridizations of total RNA probed with PMA1 gene. The presence of sub-lethal concentrations of ethanol enhanced the expression of PMA2 whereas it reduced the expression of PMA1. The inhibition of PMA1 expression by ethanol corresponded to a decrease in the content of plasma membrane ATPase as quantified by immunoassays. Although an apparent correspondence could exist between the increase of plasma membrane ATPase activity and the level of PMA2 expression, the maximal level of PMA2 expression remained about 200 times lower than PMA1. On the other hand, ethanol activated the plasma membrane H(+)-ATPase activity from a strain expressing only the PMA1 ATPase but did not activate that from a strain expressing only the PMA2 ATPase. These results provide evidence that in the presence of ethanol it is the PMA1 ATPase which is activated, probably by a post-translational mechanism and that the PMA2 ATPase is not involved. PMID- 7871885 TI - Isolation and preliminary characterization of Pichia pinus mutants insensitive to glucose repression. AB - A new method for the isolation of glucose repression-insensitive mutants in the methylotrophic yeast Pichia pinus was developed. The method is based on screening of small suspension samples derived from 2-deoxyglucose-resistant colonies for alcohol oxidase activity. Alcohol oxidase activity was evaluated by determination of formaldehyde excreted by cells. Mutants with glucose non-repressible alcohol oxidase and catalase synthesis were obtained. All mutants grew poorly on D-xylose compared to the wild type, whereas growth on L-arabinose was similar to the wild type. Changes in the glucose transport system were suggested to be responsible for altered growth characteristics and defective glucose repression. PMID- 7871884 TI - The peroxisomal membrane proteins of Candida boidinii: gene isolation and expression. AB - Candida boidinii is a methylotrophic yeast in which several growth substrates can cause vigorous peroxisomal proliferation. While such diverse substrates as methanol, oleic acid and D-alanine induce different peroxisomal metabolic pathways, membranes seem to contain common abundant peroxisomal membrane proteins (PMPs). These proteins have been termed PMP31, PMP32 and PMP47. The gene encoding PMP47 has been previously cloned and analysed. We now report the isolation of a second PMP47 gene (or allele) as well as PMP31 and PMP32. PMP47A and PMP47B share 95% sequence identity at the amino acid level. PMP31 and PMP32 each contain 256 amino acids and are highly similar (97% identity) in protein sequence. Both PMP31 and PMP32 are predicted to span the membrane once or twice. All abundant PMPs of C. boidinii are basic in charge; they all have predicted isoelectric points above 10. RNAs corresponding to the PMP47s and to PMPs31-32 are strongly induced by methanol, oleic acid and D-alanine. While the PMP47s probably encode substrate carriers, the functions of PMP31 and PMP32 from C. boidinii are still unknown. PMID- 7871886 TI - Near-stoichiometric interaction between the non-specific lipid-transfer protein of the yeast Candida tropicalis and peroxisomal acyl-coenzyme A oxidase prevents the thermal denaturation of the enzyme in vitro. AB - A 14-kDa peroxisomal-matrix protein, named PXP-18, of the yeast Candida tropicalis is a structural and functional homologue of the mammalian nonspecific lipid-transfer protein (identical to sterol carrier protein-2). PXP-18 protected acyl-coenzyme A oxidase (ACO), the rate limiting enzyme of the peroxisomal beta oxidation of fatty acids, from thermal inactivation at 48 degrees C or 70 degrees C. This effect was dose-dependent and not replaceable either by chicken egg white lysozyme, which is similar to PXP-18 (insofar as it is basic, small, and monomeric), or by bovine serum albumin, a carrier of lipids in the blood. ACO was irreversibly denatured by heat treatment at 70 degrees C for 15 min. However, when ACO and PXP-18 were similarly heat-treated, they formed a large complex at a molar ratio of PXP-18 to ACO subunit that was about one, independent of their initial ratio. This near-stoichiometric complex had ACO activity after a 500-fold dilution and was accompanied by ACO that was free of PXP-18 and indistinguishable from native ACO in size and activity. PXP-18 also protected urate oxidase, another peroxisomal enzyme, from inactivation at 66 degrees C for 15 min and facilitated the renaturation of ACO denatured by 2 M urea. These results indicated that PXP-18 is active in modulating the structure of peroxisomal enzymes in vitro. It is possible that PXP-18 functions as a stress protein or as a part of the system that keeps peroxisomal proteins intact. PMID- 7871887 TI - Sequence and function analysis of a 9.74 kb fragment of Saccharomyces cerevisiae chromosome X including the BCK1 gene. AB - In the framework of the European BIOTECH project for sequencing the Saccharomyces cerevisiae genome, we have determined the nucleotide sequence of the cosmid clone 233 provided by F. Galibert (Rennes Cedex, France). We present here 9743 base pairs of sequence derived from the left arm of chromosome X. This sequence reveals three new open reading frames and includes the published sequence (5' end and open reading frame) of the gene BCK1/SLK1/SSP31 also identified as ORFAA. Deletion mutants of two earlier unknown open reading frames J0840 and J0904 are viable and the open reading frame J0902 is essential for yeast growth. PMID- 7871888 TI - The sequence of a 22.4 kb DNA fragment from the left arm of yeast chromosome II reveals homologues to bacterial proline synthetase and murine alpha-adaptin, as well as a new permease and a DNA-binding protein. AB - We report the sequencing of a 22,470 bp DNA fragment from the left arm of Saccharomyces cerevisiae chromosome II. Thirteen open reading frames longer than 300 bp provisionally called YBL0520, YBL0401 to YBL0408 and YBL0410 to YBL0413 have been detected. Five genes were previously sequenced: COR1, encoding a core protein of the mitochondrial coenzyme QH2 cytochrome c reductase complex (Tzagaloff and Crivellone, 1986), PRS3, a proteasome subunit gene (Lee et al., 1992), ERD2, coding for a protein involved in the secretory pathway (Semeza et al., 1990), URA7, which encodes a CTP synthetase (Ozier-Kalogeropoulos et al., 1991) and the gene for the ribosomal protein L16 (Pan et al., 1993). Among the others, YBL0406 shows striking homologies to FUR4 (Jund et al., 1988) and DAL4 (Yoo et al., 1992), the uracyl and allantoin permeases; YBL0520 is a DNA-related protein, possibly involved in gene regulation; YBL0412 shares homologies with the mouse alpha-adaptins A and C; and YBL0413 is homologous to a protein of Pseudomonas aeruginosa that is likely to be involved in proline biosynthesis. YBL0401, internal to YBL0520, is probably not expressed. PMID- 7871889 TI - UBP5 encodes a putative yeast ubiquitin-specific protease that is related to the human Tre-2 oncogene product. AB - A gene from chromosome V of the yeast Saccharomyces cerevisiae has been cloned and sequenced. The deduced amino acid sequence encoded by this gene is similar to several ubiquitin-specific proteases from yeast, especially at the highly conserved domain. It is thus named UBP5. UBP5 is also closely related to the human Tre-2 and the mouse Unp oncogene products. This study adds a new member to the ubiquitin protease family and suggests that alteration of ubiquitin protease activity may result in cancer in mammals. However, disruption of the UBP5 gene in a haploid strain did not result in a noticeable phenotypic alteration. PMID- 7871890 TI - Cloning and sequence of REV7, a gene whose function is required for DNA damage induced mutagenesis in Saccharomyces cerevisiae. AB - The function of the REV7 gene is required for DNA damage-induced mutagenesis in budding yeast, Saccharomyces cerevisiae, and is therefore thought to promote replication past sites of mutagen damage in the DNA template. We have cloned this gene by complementation of the rev7-2 mutant defect, and determined its sequence. REV7 encodes a predicted protein of M(r) 28,759 which is unlikely any other protein in the NCBI non-redundant protein sequence data base, and which is inessential for viability. PMID- 7871891 TI - A 12.5 kb fragment of the yeast chromosome II contains two adjacent genes encoding ribosomal proteins and six putative new genes, one of which encodes a putative transcriptional factor. AB - The nucleotide sequence of a 12.5 kb fragment localized to the right arm of chromosome II of Saccharomyces cerevisiae has been determined. The sequence contains eight putative genes. Two of them are contiguous and represent two ribosomal protein genes: SUP46 and URP1. SUP46 is implicated in translation fidelity and encodes the ribosomal protein S13. URP1 is homologous to the rat ribosomal protein gene L21. The open reading frame (ORF) YBR1245 is similar in its N-terminal part to transcription factors like SRF and MCM1. The ORF YBR1308 shows homology with proteins of the AAA-family (ATPases Associated with diverse cellular Activities). Two genes are predicted to encode putative membrane proteins. PMID- 7871892 TI - DNA sequence analysis of a 10.4 kbp region on the right arm of yeast chromosome XVI positions GPH1 and SGV1 adjacent to KRE6, and identifies two novel tRNA genes. AB - Determination of DNA sequence in the KRE6 region of the Saccharomyces cerevisiae genome completes a 10.4 kbp section on the extreme right arm of chromosome XVI. This segment contains two additional genes, GHP1 and SGV1 (Hwang et al., 1989; Irei et al., 1991) previously assigned physically to chromosome XVI, as well as a new tRNA(Gly) gene, and a novel tRNA(Ala) gene which is flanked by a sigma element. PMID- 7871893 TI - ATP1 and ATP2, the F1F0-ATPase alpha and beta subunit genes of Saccharomyces cerevisiae, are respectively located on chromosomes II and X. AB - Southern blot analysis showed that ATP1 and ATP2 map on chromosomes II and X, respectively. Physical mapping of ATP1 and ATP2 by chromosome fragmentation showed that ATP1 is at the left end of chromosome II and ATP2 is at the right end of chromosome X. Both are located close to telomere sequences of each chromosome; ATP1 and ATP2 being approximately 30 kb and 85 kb from the respective telomeres. PMID- 7871894 TI - Current awareness on yeast. PMID- 7871895 TI - [International Journal of Food Research and Technology]. PMID- 7871896 TI - Principles of disease prevention from discovery to application. AB - This paper reviews the well-known evidence that many of our diseases today relate to lifestyle practices that have their beginning in childhood. While mechanistic understanding of a disease is of obvious value, the history of medicine has shown that preventive measures can be applied long before the pathogenesis of a disease is understood. The greatest obstacle to preventive medicine for the average person is the illusion of immortality and that each of us does not readily make a sacrifice of something pleasurable for a potential benefit in the future, and that for health professionals preventive medicine is not as economically rewarding as therapeutic practice. Hospitals, physicians, parents, and schools can all contribute to enhancing healthy lifestyle practices. We place here particular emphasis on early comprehensive school health education and strongly suggest that such educational efforts must be on par with the teaching of other subjects since good healthy habits strongly affect both children's physical and mental development and thus contribute to a more productive future society. PMID- 7871897 TI - A prospective study in a southern Indian hospital on the prescription of medication during the lying in period following childbirth. AB - The awareness of the inherent risks attached to medication use during pregnancy is increasing. There is, however, a paucity of available following childbirth. We have conducted a prospective study in women who gave birth in hospital with the objective of analysing the use of medication in this lying in period. The results show that, in addition to the vitamins and minerals routinely prescribed for every young mother and the antipyretics administered as required, the following medicaments were most often used: analgesics (by approx. 9%), anti-inflammatory agents (49%) and antibiotics (38%). The antibiotics were either used prophylactically or, in cases of proven infection, administered therapeutically. The use of antibiotics appears more intensive compared to western countries, presumably due to the greater risk of infection in this group in India. On the other hand, the use of sleep inducing medication and tranquillizers during the lying in period appears, in comparison to other studies, almost negligible. The majority of the women were unaware of the potential side-effects of medication during breastfeeding. PMID- 7871898 TI - [Knowledge, attitude and behavior of Tunisian women apropos of gynecological cancers]. AB - With the aim to analyze population needs in the field of cancer screening (cervical and breast cancer), attitudes, behaviors and knowledge of a Tunisian women group of health service user's were studied. Results clearly demonstrate the necessity to inform the concerned population about risk factors particularly concerning breast cancer (the most frequent cancer in Tunisia) but also early symptoms and available screening methods. This role is alloted to health professionals, more for general practitioners and midwives than for gynaecologists. Health education for women and groups, however, have to go hand in hand with training of health professionals in matter of test screening. PMID- 7871899 TI - [Incidence of femoral neck fractures in the German Federal Republic in comparison to other countries]. AB - Reported age-adjusted incidence rates vary markedly in Europe and the US, making the transposition of results from elsewhere questionable. The aim of this study is to fill this gap and to compare the hip fracture incidence between Germany and other countries. Population-based epidemiologic research was conducted in Duren (84251 residents), because its population is representative for West Germany as far as age and social structure are concerned, and because medical care is virtually self-contained within the community. Patient files and discharge statistics of the three local hospitals were thoroughly reviewed. Hip fractures after adequate trauma and pathological fractures were excluded. Between 1987 and 1989 276 inadequate hip fractures were identified among the resident population. There was a highly significant increase in the age-specific incidence of hip fractures in both sexes, but females were more frequently affected (crude average annual incidence rate per 100,000: females 291.3 males 110.2). The age-adjusted incidence rates for Germany in comparison to published international data follow on third position after the high rates reported for Norway and the US. The annual incidence of 70,000 hip fractures for the former Federal Republic of Germany is significantly higher than expected. PMID- 7871901 TI - [30 years of public health in Switzerland: a historical glimpse]. PMID- 7871900 TI - [Smoking among children and adolescents: a challenge for primary prevention]. AB - The best way to prevent the deleterious health effects of cigarette smoking is helping children to refrain from starting the habit. As a part of a survey of the prevalence of asthma symptoms in children and adolescents, we investigated the smoking habits of grade seven and eight school children in Bochum, a city of approximately 400,000 people in northwestern Germany. A random sample of 2050 children (93%) answered a confidential questionnaire. Fifty-three percent of the children responded that they had ever smoked cigarettes and 26% indicated that they had smoked during the previous month. 10% of the teenagers smoked daily, and 5% smoked more than 10 cigarettes per day. The prevalence of active smoking during the previous month was more frequent among girls (28%) than among boys (23%), but slightly more boys (5%) than girls (4%) smoked more than 10 cigarettes per day. The prevalence of active smoking was increased among children living in families of lower socio-economic status or in households with smokers. The high prevalence of cigarette smoking among the school children in Bochum, Germany, emphasizes the need to develop and implement effective intervention programs for children and adolescents and to contribute to a social environment which is conductive to refraining from smoking. PMID- 7871902 TI - Probing the future. PMID- 7871903 TI - World Health Organization urges sex education in schools to prevent AIDS. PMID- 7871904 TI - [Antinuclear antibodies in rheumatology]. AB - Antinuclear antibodies are autoantibodies which are hallmarks of connective tissue diseases. They are directed against intracellular antigens. As a first step of the diagnostic procedure, screening for antinuclear antibodies is performed on HEp-2 cells as a substrate. Different immunofluorescence patterns such as homogeneous, rim-like or speckled can be seen and the antibody titer is determined. In a second step of the diagnostic procedure the antinuclear antibodies are differentiated into defined species. Systemic lupus erythematosus, Sjogren's syndrome, mixed connective tissue disease, polymyositis and dermatomyositis are characterized by disease-specific antibody profiles, which can be measured by different methods such as ELISA or immunoblotting. For clinical purposes the most important antinuclear antibodies are antibodies against double stranded DNA, Sm, RNP, SS-A, SS-B, centromere proteins and Jo-1. The importance of antinuclear antibodies lies in their disease-specific profiles which are helpful for diagnosis. At present, it is not known if antinuclear antibodies are involved in pathogenesis of connective tissue diseases. PMID- 7871905 TI - [Therapy of generalized tendomyopathy (fibromyalgia) caused by blocking 5-HT3 receptors]. AB - In more than 40% of patients with fibromyalgia a marked influence on the pain in the skeletal system with a decrease of the tenderness at "tenderpoints" can be achieved by blocking the 5-HT3-receptors with ondansetron or tropisetron hydrochloride. Physical complaints and vegetative signs also improve. It is discussed if patients not responding to therapy with ondansetron or tropisetron hydrochloride have to be discriminated as a subgroup of fibromyalgia. More investigations are needed to confirm the described effects. PMID- 7871906 TI - [Systemic lupus erythematosus in men--a different prognosis?]. AB - A retrospective analysis of 21 male and 82 female patients with systemic lupus erythematosus (SLE) was performed in order to identify sex-linked differences in disease manifestations. As organ manifestation, cardiac involvement was assessed in 12 of 21 male patients (57%) and in 18 of 82 females (22%; p < 0.05). Renal involvement occurred in 16 male (76%) vs 26 female patients (32%; p < 0.05). Endstage renal disease developed in 5 of the 21 men (24%), but only in 6 of the 82 women (7%) with SLE. The most striking clinical result was the high frequency of thrombembolic complications in male SLE-patients. Twelve out of 21 males (57%) experienced more than 30 thrombembolic events in contrast to 9 events in 5 out of 82 females (6%; p < 0.0001). Persisting elevated IgG-anti-cardiolipin antibodies were found in 48% of male and only 16% of female patients (p < 0.05). In conclusion, these data suggest that SLE in males is characterized by more frequent and severe organ involvement and especially by striking prevalence of partly life-threatening thrombembolic complications. PMID- 7871907 TI - [Incidence of acral nodulosis with long-term methotrexate therapy in patients with inflammatory rheumatic diseases]. AB - The significance of acral nodulosis under methotrexate therapy is still controversial. Among patients with rheumatoid arthritis and methotrexate therapy this manifestation could be observed in 8/163 (5%). All cases were seropositive and already treated with other LAAD. Patients with other inflammatory rheumatic diseases under methotrexate therapy (n = 83) did not develop this nodulosis. The acral nodulosis is interpreted as a typical side-effect of methotrexate only in patients with rheumatoid arthritis. Histopathologically, these nodules do not differ from the typical rheumatoid nodule. PMID- 7871908 TI - The supercilium acetabuli score: an additional criterion for estimating the biomechanics of the hip joint. AB - There are significant correlations between the surface of the acetabular roof sclerosis (supercilium acetabuli) in the hip joint on a normal a.p. radiograph and the corresponding surface of cartilage. This correlation can be defined through mathematical formulas and scaled afterwards. These scales are determined on the basis of our clinical experience with the new supercilium acetabuli score. The score is related to the biomechanical situation of the hip joint and describes 3 classes: Class I = optimum, class II = balance, class III = imbalanced correlation between the supercilium acetabuli and the corresponding part of the joint space. For simple measurement of both surfaces, we developed a measuring instrument, the superciliometer, with which it is possible to obtain standardized conclusions describing the functional morphology of the cartilage in the pressure distribution zone of the hip joint, irrespective of whether there are already any visible radiological signs of coxarthrosis or not. PMID- 7871909 TI - [Surgical hysteroscopy: complications, safety aspects, education and training]. AB - Hysteroscopy has become an integral part of the overall gynaecological surgical concept. On the one hand the experience of our study group as well as a literature survey have demonstrated that results of hysteroscopic metroplasty, resection of submucous myoma and synechiolysis are at least comparable to those of conventional procedures, the advantages of minimal invasive surgery being evident. However, increasing complications, even with a lethal outcome, due to deficient technical equipment or insufficient training of the surgeon are reported. Yet, a survey of complications in literature and in our own series of hysteroscopies (n = 200), shows a median complication rate below 1%. Knowledge of possible complications, symptoms and management alternatives is, however, a first requirement for application of these minimal access procedures. The second major precondition being a well structured training program for surgeon and assisting team. With the recently developed in-vitro-simulation trainer, the HysteroTrainer, training of the entire spectrum of hysteroscopic procedures, including laser and high frequency electrosurgical applications, is now feasible. The simulator may also be employed for security checking of the complex hysteroscopic equipment. PMID- 7871910 TI - [Variability of quantitative DNA parameters in endometrial carcinoma]. AB - We performed image analysis examinations of 20 cases of endometrial carcinoma and the compared quantitative DNA parameters within each carcinoma. Specimens were taken from each carcinoma, at standardised, pre-defined sites. Six smear preparations were made from each case and DNA parameters were determined after Feulgen staining. 17 of the 20 cases of endometrial carcinoma (85%) showed in all the examined preparations a uniform diploid or aneuploid (n = 1) DNA distribution. Only 3 carcinomas showed diploid as well as non-diploid DNA distributions. For each carcinoma the mean values of DNA-MG were found to be between 0.37 +/- 0.12 and 2.16 +/- 0.11 and those of the 5cER between 0.91 +/- 0.78 and 15.37 +/- 4.17. Relationships were shown between DNA distribution, DNA MG, 5cER and morphological prognostic factors while a reliable diagnostic of dignity based on DNA distribution and 5cER as a marker of single cell ploidy seems not possible. With an increase in DNA-MG, the coefficient of variation of this parameter decreased within the individual cases. Concluding, quantitative DNA parameters, owing to their relatively small variability within specific cases of endometrial carcinomas seem to be suitable objective indicators of prognosis to plan a risk-adapted therapy. PMID- 7871911 TI - [Characteristics and adequate clinical management of "ovarian cysts"]. AB - Early diagnosis resp. prophylaxis of ovarian cancer is possible by removal of all postmenopausal cysts (adnexae plus cystic pathology) of more than 3 cm diameter and of premenopausal cysts showing persistence or progression after 6-8 weeks of sonographic control after the primary examination. The presented retrospective study revealed 2.5% malignancy in premenopausal cysts and 19.5% in the postmenopause. The removal of intact cysts is mandatory. Different technical methods are discussed. In the presented study there were no false negative findings, the rate of unnecessary operations was 5.6%. PMID- 7871912 TI - [Drug therapy of ovarian cysts]. AB - Medical therapy of ovarian cysts can be therapeutic and preventive. Follicle- and corpus luteum-cysts as well as endometriomas are suitable for medical treatment. Estrogen/gestagen-combinations. GnRH-analogues (GnRH-agonists, gnRH-antagonists), gestagens and danazol can be used. For therapy of ovarian cysts the medical and operative options are to be considered and an individualized therapeutic strategy should be initiated. PMID- 7871913 TI - [Mild, moderate and severe dysplasia in exfoliative cytological studies of breast secretions in connection with use of oral contraceptives]. AB - In our present material of 30,000 cytologically investigated mammary secretions we have found since 1980 in 1.55% mild, moderate and severe dysplasias. Due to the high number of women using long time oral contraceptive pills are further investigations necessary. Such women using gestagen accented pills in particular with the gestagen norethisterone acetate are charged with a significant high level of dysplasias in nipple discharge. After stopping or changing the contraceptives, these dysplasias seem to be reversible. These findings should therefore stimulate further intensive examinations, in order to detect in time possible dangerous side effects after long time using of oral contraceptive pills and to avoid them. PMID- 7871914 TI - [Is there a seasonal incidence of ectopic pregnancy?--A retrospective analysis]. AB - The seasonal incidence of 472 ectopic pregnancies in the years 1984-1993 in the Departments Obstetrics and Gynaecology Greifswald and Neubrandenburg were analysed. While the birth rate was decreasing in the third and fourth quarter of the year there was a low, no significant increase of ectopic pregnancies from 1.30% (April-June) to 1.75% (October-December). The monthly analysis did not show any significant differences. In the area Vorpommern/East-Mecklenburg climatic and meteorological factors do not seem to have an important influence on the incidence of ectopic pregnancies. PMID- 7871915 TI - Antinuclear antibodies in women with recurrent pregnancy wastage and their prognostic value for immunotherapy. AB - Autoimmune diseases are suspected of causing some cases of recurrent pregnancy loss. We sought serological evidence of such diseases in women with recurrent pregnancy wastage. Antinuclear antibodies were studied administrating indirect immunofluorescence test using HEP-2 cells as targets. We compared the frequency of a low-level antinuclear antibody titers in the 68 women with a history of unexplained recurrent pregnancy losses (group A) to that in 35 with explained repeated pregnancy losses (group B) and 44 healthy pregnant (group C), and 36 healthy nonpregnant women (group D). The frequency of positive ANA tests at a titer of 1:40 or higher was 51.5% in group A, 34.3% in group B, 6.8% in group C and 5.6% in group D. No negative influence on pregnancy outcome was found in case of occurrence of ANA in group A where women were treated with husband's lymphocyte immunisation. The success rate was 78.6% in patients with positive ANA and 62.5% in patients with negative ANA. This study demonstrates a high prevalence of low-titer antinuclear antibody-positive serum in patients with both explained and unexplained pregnancy losses; however, the significance of these findings remains unclear. PMID- 7871916 TI - Antispermatozoal antibodies in human colostrum and milk. AB - Authors studied antisperm activity in human colostrum and milk by tray agglutination (TAT) and indirect mixed antiglobulin reaction (MAR) tests. Spermagglutination observed by TAT was found in 10 patients (24%) in colostrum, in 3 (5%) in milk. Character of spermantibodies by indirect MAR-test showed the presence of sIgA in 6 (14%), in IgG in 4 (9.5%) in colostrum, the presence of sIgA in 3 (4.8%), of sIgA and IgG together in 1 (1.7%) in milk. Authors discuss the origin of these antibodies. PMID- 7871917 TI - [Reaction of the anterior eye segment to preventive Crede treatment]. AB - A controversily carried discussion concerning the prophylaxis according to Crede is in process. Reviewer decline the Crede-prophylaxis. The high rate of side effects (Argentum conjunctivitis) interdicts with applications of Argentum nitricum. In a blind study we examined the reaction of the ophthalmic front region in the first 5 days after delivery in 40 neonates with and without Crede prophylaxis with Argentum nitricum. We found no significant differences in the frequency of pathological chances in the palpebra, conjunctiva bulbi et tarsi and cornea between the two groups. In the group of children, who had not been given Crede-prophylaxis there was the same frequency of palpebral edema and conjunctival hyperemia. Until there is no general screening for gonorrhea in the late pregnancy and because of lack of a better method as the prophylaxis according to Crede we can recommend the Crede-prophylaxis with argentum nitricum as an undangerous and save method for preventing gonoblennorrhea of neonates. PMID- 7871918 TI - [Possibilities for modifying risk factors for chromosome abnormalities- advantages of the so-called "triple" marker studies in comparison with pure "maternal age screening"]. AB - We have offered the so-called "triple-marker screening" since May 1991 to all patients who came for prenatal care and did not select an invasive procedure primarily. First evaluation of 5210 cases revealed that 3.7% were test-positive for neural tube defects, 13.8% for Down's syndrome and 0.5% for both at the same time. The explanation for the comparatively high "test-positive" rate of 13.5% is the maternal age distribution with the median at 31.4 years. The highest number of women selecting triple-marker determinations was in the age group of 35 years. We detected 16 cases of Down's syndrome and in this group the majority of women was below 35 years. The decision of women to have an invasive procedure was obviously very much influenced by the actual risk assessment, because amniocentesis was chosen by 72/85 (84.8%) of women with a risk of more than 1:50, 192/290 (66.2%) of women in the risk category of 1:51 to 1:200 and 182/333 (54.6%) in the risk category of 1:201 to 1:400. The follow-up is not yet complete, but there is already good evidence for the efficiency of the screening program. Triple-marker screening also proved predictive in 10 cases of trisomy 18 and 8 cases of triploidy in this series. As a cut-off value we chose the risk of 1:386 which is equivalent to the odds of a 35 year old to have a child with Down's syndrome at birth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871919 TI - [Cystic kidney dysplasia of variable expression--prenatal ultrasound, cytogenetic and patho-anatomic findings based on 3 case examples]. AB - The present study reports on 3 cases of cystic renal dysplasias of Potter II type with variable characteristics and different clinical symptoms. The prenatal sonography revealed multicystically altered kidneys in the 19th to 33 rd week of gestation. Amniotic fluid cells and fetale lymphocytes were investigated to exclude possible chromosomal disorders. In case one, a unilateral cystic renal dysplasia was diagnosed by sonography in the 19th week of gestation. The chromosome analysis revealed one additional and altered chromosome 22 (partial trisomy). In case two, a bilateral cystic renal disease with oligohydramnios was distinguished in week 21 of gestation. In both cases, the pregnancies underwent artificial abortions and the stillborn infants were subjected to post mortem examinations. The patho-anatomical examinations confirmed the results of prenatal diagnoses and the classification of the cystic renal alteration as renal dysplasia of Potter II type. In case two, extrarenal malformations were found additionally. In case three, sonography revealed a unilateral multicystic kidney. In this case, there had not been any clinical symptoms in the prenatal stage, neither originating from the affected organ nor from other disorders. After delivery at predicted day a unilateral nephrectomy was performed because of space consuming growth inside the abdominal cavity. PMID- 7871920 TI - [Cardiotocography practice case 27. H. B. 404073/1994. Fetal hypoxia]. PMID- 7871921 TI - Imre Toro (1900-1993). PMID- 7871922 TI - A pharmacological discrimination of two behavioral forms of the paradise fish (Macropodus opercularis). AB - Intracranial injections of 5 micrograms/fish (equivalent to 2 nmol/g) of the dopamine agonist Apomorphine into the paradise fish brain considerably decrease the occurrence of escape behavior with a parallel increase of time spent in swimming. All other elements of the behavioral repertoire are unaffected. The simultaneous administration of 0.5 micrograms/fish (equivalent to 0.15 nmol/g) of the dopamine antagonist Pimozide abolishes this effect. In a second experiment a dose dependent decrease in escape behavior was obtained with a parallel increase of swimming. On the bases of these pharmacological data it is concluded that the escape and the swimming reactions are truly independent units but their regulation might be closely related. PMID- 7871923 TI - The photorefractoriness in domestic goose: effect of gonads and thyroid on the development of postbreeding prolactinemia. AB - Blood samples were taken from adult male and female geese, and from gonadectomized (GX), thyroidectomized (TX) and gonadectomized+thyroidectomized (GX+TX) ones during the reproduction peak period (March 16), at the beginning of photorefractoriness (June 14), in the second half of the photorefractory period (August 14), and at the beginning of the postrefractory period (October 2). Surgeries were carried out at the age of 10-13 weeks. The birds were kept under natural light conditions. From the blood plasma prolactin (PRL), luteinizing hormone (LH), testosterone (T), progesterone (P4), 17 beta-oestradiol (E2) as well as thyroxine (T4) and triiodo-tironine (T3) were determined by RIA methods. At the beginning of photorefractoriness in intact geese the LH and E2 levels significantly decrease, relative to sexually active period, whereas the P4 remains at a high level. In ganders the LH shows only a slight decrease but the T level is significantly lower than in spring. The PRL, T4 and T3 levels increase after reproduction and give a peak value in both sexes. In both GX ganders and geese decreased T, P4 and T3 levels are observable and the PRL is decreased in females, and the LH is increased in both sexes. Gonadectomy does not influence the E2 in females, the PRL in males and the T4 in both sexes. In TX birds the PRL is higher in March and lower in June than the control level, but these changes are significant only in females. In TX females the P4 level is lower during reproduction and at the beginning of photorefractoriness. The T and E2 levels do not change during the photorefractoriness. In the second half of photorefractoriness a low PRL and P4 level, an increasing LH, T and medium high T4 and T3 levels characterized the intact male and female geese. In GX animals an increase of LH levels is occurred in both sexes. The T4 is higher in castrated-, and lower in ovarectomized geese. In TX birds the P4 is higher than in controls, but the difference is significant only in males. The levels of PRL, LH, T and E2 remain unchanged in TX animals. At the beginning of the postrefractory phase the T (in males) and the P4 and the T4 level increase in both sexes. The PRL and LH show a low value. In GX animals the high LH level refer to the increased sensitivity of hypothalamo-gonadotropic system, because of the absence of negative feed-back of sexual steroids.4+ in both sexes and a high thyroid hormone level and a transitional slight reactivation of gonadotropic-gonadal system occur then. PMID- 7871924 TI - Immunocytochemical demonstration of progesterone and estrogen receptors in feathers and skin of adult hens. AB - Clinical evidence indicates that ovarian steroids are involved in the control of moulting in the chicken. This immunocytochemical study investigates if feather papillae and growing feathers are target tissues for ovarian steroids. Progesterone (PR) and estrogen (ER) receptors were demonstrated using monoclonal antibodies in feathers and surrounding skin of laying hens. Both receptor types were present in the nuclei of dermal papillae and in the nuclei of the epidermal germinative layer cells of growing and full-grown feathers. In growing feathers most nuclei of the intermediate layer (ramogenic column, rachis, axial plate) were immunostained, but during the final stages of differentiation into barbules, only estrogen receptors remained prominent. Skin adjacent to feathers showed ER and PR receptors in nuclei of cells from epidermis, muscles and arteries. During egg-laying pause, plasma progesterone levels decrease ten-fold and it is supposed that this results in a much greater endocrine efficiency of the remaining estrogen levels which are only reduced by 50% when egg-laying stops. The moult inhibiting effect of progesterone in laying hens could be due to its well established downregulation on estrogen receptors and therefore, on the endocrine effect of ER at cellular level in feather papillae. Such may account for the presence of both receptor types on the same feather cells, as observed in the present study. PMID- 7871925 TI - Routine oxygen consumption in different sizes of a tilapia, Oreochromis niloticus (Trewavas) using the closed chamber respiratory method. AB - Routine oxygen consumption (Vo2) measurements on 54 specimens (0.055-190.4 g) of a tilapia, Oreochromis niloticus (Trewavas) were carried out using two different types of closed respirometers: a modified cuvette for fish weighing 0.055-0.91 g and ordinary closed chamber respirometer for fish weighing more than 1 g. Vo2 values over the weight range studied had a scaling value of 0.743 which relates closely to the values for the gill respiratory surface area and morphometric oxygen diffusing capacity of O. niloticus in a previous study /13/. This shows that a close relationship exists between changes in structural parameters involved in oxygen uptake and the routine metabolism of O. niloticus with development. The values for routine Vo2 of 1.38 and 7.65 ml/h for 10 g and 100 g fish, respectively (calculated from the regression equation) show that O. niloticus is a moderately active fish. PMID- 7871926 TI - Effect of sublethal concentration of mercury and zinc on the energetics of a freshwater fish Cyprinus carpio (Linnaeus). AB - Exposure of a freshwater fish Cyprinus carpio to the sublethal concentration of mercury (0.1 mg L-1) and zinc (6.0 mg L-1) resulted in distinct changes in the energy metabolism of gill, liver and muscle at 1, 15 and 30 days. The changes were: (a) The rate of oxygen consumption and SDH activity decreased in the organs of mercury-exposed fish at all the three exposure periods in the order 1 > 15 < 30 days. Whereas, an increase was observed in these parameters in the organs of zinc-exposed fish in the order 1 > 15 > 30 days. (b) The activity of LDH and the levels of pyruvate and lactate increased in all the three organs of the fish at the three exposure periods studied in both the metal media. But, this increase was also in the order 1 > 15 < 30 days and 1 > 15 > 30 days in the organs of the fish exposed to mercury and zinc, respectively. (c) The results indicated greater reliance of mercury exposed fish on the energetically less efficient anaerobic glycolysis as the oxidative metabolism suppressed, and the dependency of zinc exposed fish on both the oxidative and anaerobic glycolytic pathways in order to meet the energy requirements. On prolonged exposure zinc-exposed fish could adapt to sublethal toxic stress, such type of adaptive-response was not observed in mercury-exposed fish. PMID- 7871927 TI - Metal transfer in marine food chains: bioaccumulation and toxicity. AB - Metal transfer in marine food chains may be examined at different scales from field studies to cellular level. Some years ago, the major question was to verify the existence of metal biomagnification, a phenomenon which seems in fact to be limited to mercury and the radionuclide cesium-137. In numerous cases, metal incorporation is not determined chiefly by the trophic level in the food chain. It is also controlled by both the metabolic characteristics of species or populations and the biological role of each element. The most accurate assessment of trophic transfer may be by determining the physico-chemical state of metals in marine organisms, a methology which can be used for both field and experimental samples. Some species exhibiting high detoxication ability may be interpreted as highly contamined links in food chains but according to the nature of the detoxifying ligands--in outline, mineral granules or metalloproteins--the bioavailability to the next trophic level may vary widely. PMID- 7871928 TI - Induction of in vitro tuberization by short day period and dark treatment of potato shoots grown on hormone-free medium. AB - Effects of an environmental factor, the photoperiod, on tuberization were analyzed in vitro on 7 different potato cultivars from various maturity groups and genetic origin. No growth regulators were added to the culture medium, to preserve natural endogenous equilibrium of hormones. After culturing of shoots for 4 weeks under long days, tuberization was induced with pouring of 8% sucrose solution onto the cultures and five different photoperiodic treatments consisting of different combinations of short days and total darkness. Light (8 h) during tuber induction delayed tuberization, while the dark treatment (0 h) after short days (8 h) promoted a rapid tuber initiation. The beginning of tuberization could not be correlated with maturity groups. In vitro tuber formation has occurred at a rate of at least one tuber per plantlet and this tuberization rate were at least as high as any method previously described based on the addition of growth regulators. This would indicate, that photoperiod controlling tuberization processes in vivo, trigger a general state of induction in plantlets cultured in vitro. PMID- 7871929 TI - High-efficiency plant regeneration from an embryogenic cell suspension culture of winter wheat (Triticum aestivum L.). AB - Highly embryogenic cell suspension cultures were established from immature embryo derived embryogenic calli of winter wheat (Triticum aestivum L., cv. GK Sagvari). Weekly subcultures were made in liquid MS medium supplemented with 2 mg 1(-1) 2,4 D. An average of twenty-two compact, organized calli were obtained from each 1 ml suspension cells when plated on solid MS medium containing IAA and zeatin under a 16/8 h light/dark cycle, while only 9 calli were produced in the dark. Variation in the callus inducing ability was correlated to the time elapsed after subculture. Plated cells responded best 9 days after the subculture and 59% of the calli were regenerable, retaining their embryogenic capacity over 6 months. Several hundred green shoots and plants were regenerated on differentiation media supplemented with IAA and BAP, and 300 plants were transferred to the greenhouse. The majority of plants had an abnormal chromosome number and a low viability. PMID- 7871930 TI - Functional connection between intracellular and extracellular secretion in species of Euphorbia genus. AB - In species of the Euphorbia genus the intracellular latex-secretion and the extracellular nectar-secretion are anatomically connected. The functional connection of the secretional systems was proved to be probable by TLC and GC MSD. The chemical composition of Euphorbia latex and honey was examined with these analytical methods. In our research, the comparative chemical analysis of the latex and the honey of two Euphorbia species (Euphorbia cyparissias L., Euphorbia seguieriana Necker.) was discharged. These species are unusually good melliferous plants in Hungary. Four chemical components that can be found both in the latex and in the honey were detected with ultraviolet light (254 nm), and three general alkaloid reagents (Dragendorff, Meyer and 1% Ce(SO4)2 in 2n H2SO4) were detected by TLC. By means of mass spectrum generated by GC-MSD, the following compounds of Euphorbia honey were identified: butyl-2-methylpropyl phtalat, hexadecane acid, diheptyl phtalat, bis (2-ethyl-hexyl) phtalat, benzenedicarboxylic acid decyl-hexyl ester, benzenedicarboxylic acid isodecyl octyl ester. The first compounds can also be found in the latex of both examined Euphorbia species. This partial correspondence in the composition of the latex and the honey led to results that suggest a further, functional connection between the two, anatomically connected secretional systems. PMID- 7871931 TI - Prophylaxis of endocarditis. PMID- 7871932 TI - Insulin antibodies before and 1 year after the change-over from U40 to U100 insulin preparations in Belgium. AB - In 1991, Belgium realized, on a national level, a change-over from U40 to U100 insulin. We took advantage of this evolution to investigate the consequences of changing the concentration of insulin. The patients' weight, daily insulin dosis, insulin binding-capacity of plasma and glycated hemoglobin HbA1c were registered before, and after the change of concentration. Overall, none of these parameters underwent an obvious change, except for the percentage of insulin binding that significantly decreased after the adaptation. Especially in the range of 40% or more insulin binding, the decrease becomes very pronounced. In conclusion, changing the insulin concentration from U40 to U100, did not lead to any harmful clinical consequence. On the contrary, a positive influence of this adaptation, in terms of decreased amount of insulin antibodies was suggested. Probably this decrease is not clinically relevant, since neither the glycated hemoglobin, nor the total daily insulin dose underwent a similar change. PMID- 7871933 TI - In vitro susceptibility of recently isolated respiratory tract pathogens to minocycline and comparable antibiotics. A multicentre study. AB - The in vitro susceptibility of recently isolated respiratory tract pathogens (217 S. pneumoniae, 202 H. influenzae and 178 M. catarrhalis, has been examined against minocycline, doxycycline, amoxycillin, amoxyclavulanate, cefuroxime, clarithromycin and ciprofloxacin. M. catarrhalis was fully susceptible to all antibiotics except amoxycillin (62% susceptible). H. influenzae showed full susceptibility to minocycline, cefuroxime and ciprofloxacin but different percentages of resistance to the other antibiotics. Among S. pneumoniae isolates resistance was observed to all antibiotics tested between 12% to beta-lactams and 22% to doxycycline. PMID- 7871934 TI - Pathogenic tracks in fatigue syndromes. AB - This review analyses the recent literature devoted to two related fatigue syndromes: chronic fatigue syndrome (CFS) and acute onset postviral fatigue syndrome (PVFS). The articles are grouped into five pathogenic tracks: infectious agents, immune system, skeletic muscle, hypothalamo-pituitary-adrenal (HPA) axis and psychiatric factors. Although a particular infectious agent is unlikely to be responsible for all CFS cases, evidence is shown that host-parasite relationships are modified in a large proportion of patients with chronic fatigue. Antibody titres against infectious agents are often elevated and replication of several viruses could be increased. Chronic activation of the immune system is also observed and could be due to the reactivation of persistent or latent infectious agents such as herpes viruses (i.e. HHV-6) or enteroviruses. It could also be favorised by an impaired negative feedback of the HPA axis on the immune system. A model is proposed where the abnormalities of the HPA axis are primary events and are mainly responsible for a chronic activation of the immune system which in turn induces an increased replication of several viruses under the control of cellular transcription factors. These replicating viruses together with cytokines such as TNF-alpha would secondarily induce functional disorders of muscle and several aspects of asthenia itself. PMID- 7871935 TI - Physiopathology of hypernatremia following relief of urinary tract obstruction. AB - We report a case of postobstructive hypernatremia, and illustrate its pathogenesis and treatment. Physicians should be aware of this condition, given its high mortality rate (up to 70%), the high prevalence of potentially obstructive prostatic disease in elderly people and the peculiar sensitivity of this age group to disorders of osmotic regulation. Knowledge of the processes involved in osmoregulation has provided insights into the pathogenesis of this condition, which includes at least three factors: (i) decreased efficacy of the thirst mechanism in elderly patients, (ii) water loss in excess of effective solutes, resulting from osmotic diuresis from urea and transient renal tubular unresponsiveness to antidiuretic hormone, and (iii) inadequate fluid administration and failure to induce a positive fluid balance. These insights led to the development of specific strategies aimed at adequate correction of hypernatremia. Initial therapy should be rapid infusion of normal saline (or half normal saline) coupled to administration of free water to restore euvolemia and correct hypernatremia, relying on repeated calculations of the free water deficit and taking into account ongoing urinary and insensible losses. PMID- 7871936 TI - Diagnostic usefulness of radiolabeled pentetreotide scintigraphy and therapeutic efficiency of octreotide in a case of insulinoma. AB - Although the functional diagnosis of insulinoma is quite easy, its topographic diagnosis still constitutes a major challenge since conventional radiological techniques, e.g. ultrasonography, computed tomography and even selective angiography, fail to recognize the tumor in numbers of insulinomas. We report an observation of a benign insulinoma in an 81-year-old woman that escaped detection by ultrasonography and CT but was later localized by both endoscopic ultrasonography and somatostatin receptor scintigraphy. It illustrates the usefulness of such recent imaging techniques for the localization of islet cell tumors that escaped detection by ultrasonography and CT. Moreover, in our elderly patient who refused surgical intervention, hypoglycemia was corrected by octreotide administration emphasizing the predictive value of 111In-pentetreotide scintigraphy on the subsequent response to octreotide therapy in patients in whom the optimal treatment (surgical resection) is not possible. PMID- 7871937 TI - [Anatomo-clinical conference: fever in a patient on dialysis]. PMID- 7871938 TI - [Cholestatic jaundice due to ticlopidine: a new case]. PMID- 7871939 TI - Amoxycillin/clavulanate and Haemophilus influenzae. PMID- 7871940 TI - Mirror imaging in twins: biological polarization--an evolving hypothesis. AB - This study examined sleep patterns in twins, paying special attention to the mirroring phenomenon. Concordance and discordance of sleep related patterns (parasomnias) in a group of 27 monozygotic (MZ) mirror image twins were compared to sleep patterns in a group of 53 MZ non-mirror image twins and a group of 24 dizygotic (DZ) twin pairs. Sleep patterns had the lowest concordance among MZ mirror twins. "Mirroring" was observed not only in facial features but also in some physiological patterns such as sleep and sleep deviations. These facts suggest that mirroring in MZ twins is not merely a superficial epiphenomenon, but a reflection of a biological polarization. Biological polarization in this context is a descriptive term emphasizing the role of biological (physiological, biochemical or even genetic) versus psychological or environmental factors causing not only mirror body image but opposite tendencies in the development of personality, professional and sex orientation and, most importantly, the opposite presentation of pathology. PMID- 7871941 TI - Genetic and environmental effects on blood cells. AB - In a sample of 105 concordant sex MZ and DZ twin pairs, the following characteristics were measured: red cell count, haemoglobin concentration, package cell volume, mean cell volume, mean cell haemoglobin, mean cell haemoglobin concentration, reticulocytes, platelets, white cell count and the six types of leucocytes, lymphocytes, monocytes, band and segmented neutrophils, eosinophils and basophils. The statistical model employed in the univariate twin analysis allows for three sources of variation: genetic (h2), shared environmental (c2) and specific environmental influences (e2). A genetic component was significant for red cell count, haemoglobin and mean cell haemoglobin (0.64, 0.60 and 0.46 respectively), with heritable variation suggested for package cell volume, mean cell volume, mean cell haemoglobin, lymphocytes and monocytes. Shared environmental variation was only present for neutrophils. PMID- 7871942 TI - "Silent" patent ductus arteriosus and bronchopulmonary dysplasia in low birthweight twins. AB - During a screening protocol of early echocardiographic diagnosis (ATL MK 600) and treatment of "silent" PDA in RDS preterms with BW < or = 1.750 kg, clinical data on premature twins were collected, including diagnosis of both PDA and BPD, to investigate whether twin birth influences PDA incidence and BPD development. Out of the 290 RDS preterms evaluated, 96 (33%) showed evidence of PDA, and a total of 79 (27%) developed BPD, 47 (16%) with associated PDA and 32 (11%) without PDA. Out of 238 singletons, 74 (31%) presented "silent" PDA and a total of 75 (31%) developed BPD, 44 (18%) with associated PDA, and 31 (13%) without PDA. In 52 other twins (18% of the total number of babies studied), 22 (42% of this subgroup) presented evidence of "silent" PDA, and 4 (8% of the subgroup), developed BPD, 3 with associated PDA (6% of the subgroup), and 1 without PDA (2% of the subgroup). From these data, it is inferred that that low-birthweight twins are at high risk for PDA hemodynamic complications during RDS, and may benefit from early induced ductal closure. Instead, in RDS twins, BPD was statistically less frequent (at the 99% C.L.) probably because twinning enhances fetal lung maturity, influencing enzymatic and nonenzymatic protective systems of lung defence. PMID- 7871943 TI - The incidence of superfecundation and of double paternity in the general population. AB - It is estimated that at least one dizygotic (DZ) twin maternity in twelve is preceded by superfecundation (the fertilization of two ova by sperm from different coitions). Presumably this parameter varies from population to population eg. with coital rates and rates of double ovulation. Sometimes superfecundation occurs by two different men. The frequency with which this occurs must depend on rates of infidelity (promiscuity). It is suggested that among DZ twins born to married white women in the U.S., about one pair in 400 is bipaternal. The incidence may be substantially higher in small selected groups of dizygotic twin maternities, eg. those of women engaged in prostitution. PMID- 7871944 TI - Life expectancy of monozygotic and dizygotic twins. AB - White male twins from the NAS-NRC twin sample, who were born in the U.S. between 1917 and 1927 and served in the military, are used to estimate variability in hazard functions for those twins who died during the period 1974-1990. Roughly the same number of MZ and DZ twins died during this period, but their death rates are similar. DZ twins exhibit greater within-pair variation. Using hazard and other analyses, the only statistically significant variables are found to be being a DZ twin (in level equations), date of birth, and, sometimes, wife's religious preference. Variables not significant for level or within-pair equations, include own religion, parental education, working overtime frequently, and number of children. The greater variation in life expectancy of DZ twins is hardly surprising and may say something about the lack of comparability in phenotype variance of DZ twins, which in turn may be worrying. PMID- 7871945 TI - Physical growth of Japanese twins. AB - The present study aimed at clarifying the characteristics of twins' physical growth. First, 557 pairs of normal Japanese twins were analyzed according to the following three life stages: (1) intrauterine growth, (2) body weight and height from birth to 6 years, and (3) body weight and height at school age (from 6 to 11 years). The following results were obtained. 1. Intrauterine growth of twins was very different from that of singletons, especially as regards weight, so twins should be estimated by twin standards. 2. Size deficit at birth was appropriately recovered over the first 6 years. 3. No size deficit was observed by school age. Second, the similarity of bodyweight and height according to zygosity was analyzed using 605 pairs of normal Japanese twins, 427 monozygotic (MZ), 113 same sexed dizygotic (DZ) and 65 opposite-sexed DZ pairs. The similarity between MZ and DZ pairs was almost the same at birth. However, MZ pairs became increasingly more similar with age, whereas DZ pairs became more dissimilar. This tendency was very clearly seen through early infancy, thus suggesting that genetic factors became more apparent during this life stage. PMID- 7871946 TI - Changing trends in twinning. AB - Birth statistics (on 13,887.943 births) from 11 Indian States indicate a fall in the dizygotic twinning rate and a rise in the monozygotic twinning rate over the decade between 1982 and 1991. These figures seem to reverse the trend of the period 1960-1982. One plausible explanation is offered by the age-data on mothers, which indicate that twins of different sex are more frequently born to mothers above the age of 35. Since extensive family planning measures have reduced the upper age-limit of mothers, the birth-rate of twins of different sex has also fallen. Due to the increased proportion of twins of the same sex, Weinberg's differential method will therefore report a decline in the dizygotic twinning rate, wherever the mean age of mothers has fallen (i.e. most mothers do not reproduce after the age of 35). PMID- 7871947 TI - Latent menstrual cycle in pre-menarcheal monozygotic twins. AB - The distribution of menarcheal interval-length between cotwins in 67 pairs of female identical twins in Tokyo was found to cluster at fairly constant intervals. When delayed in one twin, the menarche occurred in the second twin at intervals of approximately 28 days after that of the earlier twin. This finding suggests the existence of a latent lunar or menstrual cycle in pre-menarcheal girls, evidence for which was detected by recording the menarcheal intervals between MZ cotwins in days. PMID- 7871948 TI - Changes in immunological properties of neutrophil alkaline phosphatase in trisomy 21 pregnancies. AB - Immunoreactivity, cytochemical, immunocytochemical characteristics and subcellular distribution of neutrophil alkaline phosphatase (NAP) were investigated in blood and/or smear samples from 18 women aged 23-46 years (mean 32.5 years) with trisomy 21 fetuses (17-21 weeks) and 28 women aged 20-42 years (mean 31 years) with normal fetuses (17-22 weeks). Immunochemical NAP investigations were carried out in 8 pathological and 8 normal pregnancies; cytochemical and immunocytochemical procedures were carried out in 18 pregnant women with trisomy 21 fetuses and 28 controls. NAP from women with trisomy 21 fetuses is characterized by: (1) a significant decrease in reactivity with anti liver-type alkaline phosphatase (AP) and anti-NAP antisera; (2) low or very slight reactivity with antiplacental or anti-intestinal antibodies; (3) marked dispersion of NAP lead citrate reaction products or anti-NAP antibody colloidal gold-labelling in neutrophil cytoplasms, as detected by electron microscopy. This subcellular AP distribution (extramembranous) is different from that of normal NAP sites associated with plasma membrane, nuclear membrane and secretory vesicles. The NAP immunochemical and cytochemical characteristics suggest that neutrophils of a woman with a trisomy 21 fetus contain two AP isoenzymes: the liver/bone type and an atypical AP. PMID- 7871949 TI - Hematuria in sickle cell anemia--not always benign: evidence for excess frequency of sickle cell anemia in African Americans with renal cell carcinoma. AB - Between 1952 and 1992, we identified 117 African Americans with renal cell carcinoma (RCC) at the University of Chicago. Three of these had sickle cell disease (SS) and 11 had presumed sickle trait (AS). Based on genotype frequencies, these represented a 16.7-fold excess of SS patients (p < 0.0001), but the incidence of AS patients was as expected. In addition, the median age for the SS patients at presentation with RCC (36 years) was significantly less (p = 0.04) than for the AS patients (55 years). We have found no prior reports of SS in RCC patients and suggest that chronic renal injury from sickling and possible immunosuppressive effects of multiple red cell transfusions may be risk factors. We also suggest the need to be aware of the possibility of RCC in SS patients who may have hematuria solely related to sickling. PMID- 7871950 TI - High incidence of conservative RAS mutations in acute myeloid leukemia. AB - RAS mutations are found in about 25% of acute myeloid leukemia (AML) cases. The importance of these changes is unknown. If RAS mutations confer growth advantage to leukemia subclones in which they emerge, substantially more nonconservative than conservative mutations should be found. The incidence of conservative mutations was not reported previously. We sequenced N-RAS and K-RAS codons 12 and 13 and N-RAS codon 61 in 20 subjects with newly diagnosed AML. Four nonconservative N-RAS mutations and 4 conservative K-RAS mutations were found. There were no differences between subjects with AML and nonconservative RAS mutations and those with conservative or without RAS mutations. Additional studies are needed to examine the incidence of conservative RAS mutations in subjects with AML. PMID- 7871951 TI - Coincidence of severe aplastic anaemia with multiple sclerosis or thyroid disorders. Report of 5 cases. AB - Five patients with severe aplastic anaemia (SAA) who, simultaneously (n = 3) or consecutively (n = 2), presented with multiple sclerosis (MS) (n = 2) or immune hyperthyroidism (IHT) (n = 2) or subacute thyroiditis (n = 1) are described. Two female patients with MS developed SAA after a small dose of azathioprine. Another patient simultaneously presented with IHT and SAA. SAA and MS responded to cyclosporine while IHT required 131I. Relapsing SAA in 1 patient with MS was treated with antithymocyte globulin (ATG) which induced acute exacerbation of MS. Despite the low total dose of ATG (31.5 mg/kg), complete remission of SAA was obtained. Two other patients developed thyroid disorders, 42 and 106 months after successful immunosuppression with ATG/high-dose methylprednisolone. IHT and subacute thyroiditis were successfully treated with 131I or prednisolone, respectively, without recurrence of SAA in both cases. These are the first documented cases of SAA evolving in the course of MS while the coincidence with IHT was already described. Since enhanced expression of interferon-gamma plays a crucial role in SAA as well as in MS and in IHT, similar pathogenetic principles may apply for these seemingly unrelated disorders. PMID- 7871952 TI - Acute rhabdomyolysis complicating viridans streptococcal shock syndrome. AB - A 20-year-old male underwent an allogeneic bone marrow transplantation for acute myelogenous leukemia after conditioning with cyclophosphamide and total body irradiation. On day +6 of the procedure, he developed fever, chills and myalgias. Empiric treatment with ceftazidime and amikacin was begun, and blood cultures grew viridans streptococci. Biochemical changes suggestive of acute rhabdomyolysis were evident. Within 24 h, adult respiratory distress syndrome with multiorgan failure appeared, and he died 7 days later. At autopsy, the presence of rhabdomyolysis was confirmed. PMID- 7871953 TI - Arsenic intoxication presenting with macrocytosis and peripheral neuropathy, without anemia. AB - A case of arsenic intoxication associated with macrocytosis and neuropathy, without anemia, is presented. Evaluation of a 68-year-old man with a long history of peripheral neuropathy and persistent macrocytosis revealed exposure to an insecticide. Analysis of urine and hair revealed elevated levels of arsenic. A short course of d-penicillamine failed to promote urinary excretion of arsenic. Removal of the insecticide resulted in resolution of macrocytosis and slight improvement of neuropathy. This case emphasizes that arsenic intoxication should be considered in patients with macrocytosis with peripheral neuropathy, even in the absence of anemia. PMID- 7871954 TI - Myeloma with two monoclonal IgG and IgD in serum: a case report. AB - We report the case of a woman, who initially presented with an IgG kappa-type monoclonal gammopathy. An IgD-secreting myeloma was diagnosed 2 years later. The patient died of severe renal failure and infection. The discrepancy between the immunoglobulin concentration estimated from the electrophoresis pattern and the immunonephelometric measurement of IgG, IgA and IgM led us to investigate the existence of an IgD myeloma. It was of the IgD kappa type and had electrophoretic characteristics identical to the initial monoclonal IgG. A common clonal origin for these two immunoglobulins is discussed. PMID- 7871955 TI - Primary Hodgkin's disease of the bone presenting with an extradural tumor. AB - We report a very rare case of primary Hodgkin's disease of the bone in a 56-year old male. It presented with sudden onset of paraparesis which suggested an extradural tumor. Early appropriate therapy for similar patients with Hodgkin's disease can improve their prognosis. PMID- 7871956 TI - Myelodysplastic syndrome in a patient with Werner's syndrome. AB - Werner's syndrome is a relatively rare autosomal recessive disorder characterized by several features generally associated with aging. This syndrome is classified in the group of chromosome instability syndromes and there is an increased incidence of neoplasia. Hematologic malignancies associated with this syndrome are, however, unusual. Herein we report a case of Werner's syndrome with myelodysplastic syndrome, a clonal preleukemic disorder of hemopoietic stem cells. Such an association, to the best of our knowledge, has not been reported in the English literature so far. PMID- 7871957 TI - Long-term remission of neutropenia in Felty's syndrome after a short GM-CSF treatment. AB - We report a case of Felty's syndrome in which neutropenia was corrected by a short-term treatment with recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF, 5 micrograms/kg/day s.c. for 14 days). Absolute neutrophil counts rose from 0.1 to 2.2 x 10(9)/l and remained > 1.0 x 10(9)/l 8 weeks after discontinuation of the GM-CSF therapy. A flare-up of arthritis and a decrease in platelet counts were observed. PMID- 7871958 TI - Multiple cranial neuritis associated with large granular lymphocytosis. AB - A patient with a unique form of large granular lymphocytosis and multiple cranial neuritis is reported. The patient presented with facial weakness, diplopia and dysarthria. An increase in large granular lymphocytes (LGLs) was seen in blood (1.8 x 10(9)/l), CSF (237/microliters) and bone marrow (20% in a normocellular bone marrow). The phenotype of the LGLs in CSF, blood and bone marrow was CD2+ CD3+ CD4+ CD8- CD16- CD56- and CD57-. The unique features of this case include the CD4+ phenotype, the relative abundance of CSF LGL and the clinical presentation. PMID- 7871959 TI - Myelofibrosis in severe combined immunodeficiency due to vitamin D deficiency rickets. AB - An infant with severe combined immunodeficiency is described in whom a refractory anemia and thrombocytopenia developed after the age of 6 months, associated with poor growth and frequent episodes of upper respiratory tract infections and diarrhea. He required frequent blood and platelet transfusions. Bone marrow biopsy provided evidence that the anemia and thrombocytopenia were the results of myelofibrosis which was secondary to vitamin D deficiency. Therapy with 1,25 dihydroxycholecalciferol resulted in resolution of the hematologic and skeletal abnormalities, but he remained susceptible to recurrent serious infections and died at the age of 13 months. PMID- 7871960 TI - Flow cytometric analysis of T-cell-rich B-cell lymphoma. PMID- 7871961 TI - Reduced transfusion requirements in a splenectomized patient undergoing bone marrow transplantation. PMID- 7871962 TI - [Diabetes mellitus and vascular surgery: a retrospective, multivariate analysis]. AB - The influence of diabetes mellitus on the outcome of arterial reconstructions was evaluated. 25.7% of 2,735 patients (average age: 63.7 years), who underwent arterial reconstruction for arterial occlusive disease, suffered from a diabetes mellitus in need of treatment. The sex ratio within the diabetic patients was 2:1 (male:female). Regardless other influencing factors insulin-depending diabetic patients (average age: 64.6 years) were operated in average 1 year earlier than non-diabetics (average age: 65.5 years). No significant differences were found for perioperative complications. Overall, diabetic patients live significantly shorter than non-diabetics (average age: 72.8 vs. 75.8 years). Concerning the survival after the operation a stronger influence can be seen (8.3 vs. 4.4 years). The lower extremity was found to be the main localization for this negative observation on survival of patients (femoro-popliteal: 8.3 vs. 3.5 years; femoro-crural: 7.7 vs. 3.8 years). No statistical significant differences between diabetics and non-diabetics were found concerning patency rates of a reconstruction of the carotid, the aortic or the iliac arteries. There was a slight tendency pointing to a worse patency in diabetics undergoing reconstruction of the femoro-popliteal level (diabetics: 77%/1, 63%/3, 38%/5 years; non-diabetics: 80%/1, 67%/3, 58%/5 years), but this tendency did not reach statistical significance. A similar result was seen in patients with femoro crural reconstructions (diabetics: 67%/1, 51%/3, 43%/5 years; non-diabetics: 68%/1, 56%/3, 49%/5 years). We were forced to perform a major amputation significantly more often in diabetics than in non-diabetics (13% vs. 7% after 1 year).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7871963 TI - [Surgical therapy of acute thrombosis of leg-pelvic veins]. AB - A series of 213 consecutive patients suffering from acute iliofemoral vein thrombosis who underwent venous thrombectomy is analyzed. Surgery was performed from an inguinal approach with a Fogarty-balloon-catheter from the proximal vessel and by bimanual exprimation from the femoral and popliteal veins. Post operative oral anticoagulation treatment was attempted whenever possible. Long term results obtained in 130 patients after a median follow-up of 78 months (44% free of symptoms, 33% PTS [postthrombolic syndrome] I, 15% PTS II, 8% PTS III) showed a significant correlation to the duration of preoperative anamnesis: < or = 5 days: 64% free of symptoms, > 5 days: 34% free of symptoms, the rate of PTS III was equally distributed in the group with long (< or = 5 days) and short (> 5 days) anamnesis (8 and 9% respectively). Postoperative Dicumarol-therapy decreased the rate of severe PTS: 28% without, respectively 10% with therapy. If the medication was cancelled aggravation of the clinical symptoms in 1 third of the patients was observed. Venous thrombectomy is an important treatment option in patients with contraindications to thrombolytic therapy. With patients younger than 65 years and short anamnesis functional results are acceptable, high risk patients (severe cardiac disease and previous pulmonary embolism) should be treated with medical therapy only. PMID- 7871964 TI - [Citalopram in treatment of behavioral disorders in demented patients]. AB - Behavioral disturbances are a common complication in dementia. The underlying cause of this condition is mainly a disturbance of serotonin neurotransmission. In this paper the effect of citalopram on behavioral disturbances was studied in 20 patients with dementia. After 3 weeks of treatment improvement of the symptoms confusion and restlessness of the Gottfries-Brane-Steen Geriatric Scale was found (p < 0.05). These findings underline the effect of citalopram as emotional "stabilizer" in demented patients, as already described in earlier studies. PMID- 7871965 TI - [Low dosage methotrexate treatment in chronic polyarthritis]. AB - 30 patients with rheumatoid arthritis were treated with a weekly low dose of Methotrexate for a period of 12 months. In the course of treatment there was significant improvement in pain and mobility, in the number of inflamed joints and use of steroids. There was a fall in erythrocyte sedimentation rate and hemoglobin content rose significantly. 81% of the patients improved. Of these 14% had a complete clinical remission. There were 19% non-responders. Adverse reactions developed in 13 patients (43.3%, gastrointestinal symptoms, elevated liver enzymes, loss of hair, stomatitis). After decreasing or temporary discontinuing in 10 of them the drug was taken again later on. It had to be withdrawn in 3 patients (10%). All recovered when Methotrexate was discontinued. It is concluded that low dose Methotrexate is effective in the long term treatment of chronic rheumatoid arthritis. PMID- 7871966 TI - Treatment of refractory multiple myeloma with vincristine, adriamycin, dexamethasone, and with repeated application of cyclophosphamide (C-VAD). AB - The quick reduction of differentiated myeloma cells by VAD chemotherapy (vincristine, adriamycin, dexamethasone) causes, according to the investigation by Bell et al., the acceleration of the proliferation of myeloma stem cells. In 1990 Bell demonstrated that this proliferation could be stopped by administering 500 mg of cyclophosphamide in 1-week intervals. We therefore modified the classical VAD scheme to the following "C-VAD" scheme:vincristine 0.5 mg/day in continuous infusion on the first to the 4th day, adriamycin 9 mg/m2/day in continual infusion on the 1st to the 4th day, dexamethasone 40 mg p.o. or i.v. always on 4 days starting with the 1st, 10th and 20th days, cyclophosphamide 600 mg i.v. on the 5th, 10th and 20th days). A further cycle follows on the 28th day. In the present paper the effect and the tolerance of this C-VAD scheme is evaluated: In the group of 21 patients with refractory myeloma 9 remissions were achieved, 5 partial remissions, in 6 patients the disease progressed, 1 patient died after the 2nd cycle without the possibility of evaluating the therapeutic response. The mean remission length was 10.2 months. The tolerance of chemotherapy was satisfactory, C-VAD chemotherapy did not cause any serious drop in the number of leucocytes and thrombocytes. Echocardiographically lower adriamycin cardiotoxicity was demonstrated in continual administration in comparison with the bolus administration. The C-VAD scheme is considered to be suitable for comparison with the VAD chemotherapy in a randomized study. PMID- 7871967 TI - [Diagnostic process of alveolitis--state of the art]. AB - Diagnosing of alveolitis is a puzzle of many pieces, based on clinical experience and keeping in mind the criteria of extrinsic allergic alveolitis. They are antigen-exposure, typical delayed postexpositional symptoms (cough, chills, fever, dyspnea, tiredness), and serological tests of precipitating antibodies. Helpful findings are X-ray of the chest, high resolution computer tomography, auscultation findings, lowered diffusing capacity, bronchoalveolar lavage with lymphocytes > 50% and low T4/T8-ratio, histology of periphere lung specimens, and occasional inhaled provocation. Differential diagnosis are toxic lung disorders, drug adverse effects, sarcoidosis, silicosis, autoimmune alveolitis, idiopathic fibrosing alveolitis. The most frequent failure in diagnosis are common viral cold, bronchopneumonia, sarcoidosis, chronic bronchitis, and miliar tuberculosis. PMID- 7871968 TI - Biophysical properties of protein-free, totally synthetic pulmonary surfactants, ALEC and Exosurf, in comparison with surfactant TA. AB - An artificial pulmonary surfactant prepared from chloroform-methanol extract of bovine pulmonary surfactant (surfactant TA) has been shown to be effective in both the prevention and the treatment of respiratory distress syndrome in premature babies. Recently, two types of protein-free totally synthetic surfactants, artificial lung expanding compound (ALEC) and Exosurf, have been evaluated in clinical trials of surfactant therapy. Artificial lung expanding compound was used initially as a dry powder, but is now prepared as a crystalline suspension in saline at 4 degrees C. In this study we compared the biophysical properties of three different forms of ALEC (dry powder, crystalline suspension at 4 degrees C and 37 degrees C), Exosurf and surfactant TA (Surfacten) using a modified Wilhelmy surface balance and a pulsating bubble surfactometer. Surface activity of a crystalline suspension of ALEC in cold saline was no better than the dry powder of ALEC. Surfactant activity of ALEC was improved by addition of hydrophobic surfactant protein B and C (SP-B, SP-C) which are important constituents of surfactant TA. Surface properties of ALEC in any form and Exosurf were not superior to those of surfactant TA. These results suggest that a surfactant which contains SP-B and SP-C does not necessarily have to be dry or crystalline for an effective exogenous surfactant. PMID- 7871969 TI - Absence of anti-neutrophil cytoplasmic antibody (ANCA) in Henoch-Schonlein purpura and immunoglobulin A nephropathy. AB - We have studied the presence of anti-neutrophil cytoplasmic antibodies (ANCA) in 16 patients with Henoch-Schonlein purpura (HSP) and 10 patients with immunoglobulin A nephropathy (IgAN). An indirect immunofluorescence test using ethanol-fixed neutrophils as a source of antigen and an enzyme-linked immunosorbent assay using purified proteinase-3 and myeloperoxidase as antigens were used. Neither immunoglobulin G nor immunoglobulin A (IgA) ANCA were found in any of the patients studied. It was shown that fluorescein-isothiocyanate conjugated anti-human IgA antibodies bound to ethanol-fixed normal human neutrophils non-specifically, suggesting the possibility that false positive staining was responsible for the previous reports. We conclude that ANCA does not play an important role in the pathogenesis of HSP and IgAN. PMID- 7871970 TI - Urinary prolactin excretion in children with renal disease. AB - The contribution of the kidney to the metabolism of prolactin has not yet been established. In the present study, urinary prolactin concentrations in 30 children with renal disease were measured by a newly devised, highly sensitive, time-resolved immunofluorometric assay. Median prolactin concentrations in the urine of children with renal disease, were 1.86 pmol/L-1 of urine (range: 0.17 546.31 pmol/L-1. By stepwise regression analysis, change in urinary prolactin levels as a function of the urinary beta 2-microglobulin concentrations was detected. These results indicate that prolactin urinary excretion in children with renal disease is dependent on the renal proximal tubular function. PMID- 7871971 TI - Urinary excretion of acid-soluble peptides in children with Duchenne muscular dystrophy. AB - In order to investigate the validity of the hypothesis that acid-soluble peptides (ASP) in urinary excreta can be applied as an index of the protein catabolism of the whole body, we measured the urinary excretion of ASP in 46 normal children and in 18 children with Duchenne muscular dystrophy (DMD), in which continuous breakdown of skeletal muscle protein is presumed. The mean value of ASP in the children with DMD was significantly higher than that in normal controls. The concentration of ASP was correlated with that of 3-methylhistidine (3MH), which has been proposed as an index of muscle breakdown. This finding indicates that urinary ASP reflects the catabolism of body proteins. No correlation was observed between the concentration of ASP and that of 1-methylhistidine (1MH), which is used as an objective index of meat and fish ingestion. After the administration of bestatin, an inhibitor of leucine aminopeptidase, for 9 months, the urinary ASP concentration of children with DMD increased markedly. This increase is thought to have been directly caused by the bestatin itself. Urinary ASP is therefore apparently a more conveniently applied index of protein catabolism than is urinary 3MH, which requires the application of several restrictions. However, it should not be applied when the effect of bestatin administration is evident. PMID- 7871972 TI - T cell subsets in peripheral blood and cerebrospinal fluid from children with aseptic meningitis. AB - T cell subsets in peripheral blood (PB) and cerebrospinal fluid (CSF) obtained from patients with aseptic meningitis were studied using quantitative two-color fluorescence analysis with a flow cytometer. The percentage of HLA-DR+/CD3+ lymphocytes (activated T cells) in CSF was significantly increased in the recovery phase when compared to the acute phase, while no significant change in the activated T cells in PB was observed. More interestingly, CD4+ T lymphocytes in CSF were increased in the acute phase and subsequently decreased in the recovery phase. Instead, CD8+ T lymphocytes gradually accumulated into the CSF in the recovery phase, resulting in a successive decrease in the CD4/CD8 ratio. On the other hand, the CD4/CD8 ratio in PB remained normal during the course of aseptic meningitis. The present results suggest that T lymphocytes (CD4+ subset in the acute phase and CD8+ in the recovery phase) could be infiltrated and further activated at the site of inflammation, possibly in the subarachnoid space in the patients with aseptic meningitis. PMID- 7871973 TI - Inhibitory effects of diazoxide or polymyxin B on glucose transport by isolated rat erythrocytes or adipocytes. AB - The inhibitory effects of diazoxide or polymyxin B on 3-O-methylglucose uptake were studied in isolated rat erythrocytes or adipocytes to elucidate the mechanisms of the actions of these agents. One to three mmol/L diazoxide significantly inhibited 3-O-methylglucose uptake into erythrocytes by 11-33% without altering the equilibrium space, while 0.3 mmol/L diazoxide did not. The inhibitory effect was exerted in a dose-dependent manner in this concentration range. To test whether polymyxin B affects the process of insulin action or the glucose transport activity recruited by insulin, adipocytes prestimulated with insulin and exposed to 2 mmol/L potassium cyanide (KCN) were employed since the cells, on which glucose transporters recruited by insulin were located quiescently, were useful to estimate the effect of an agent on glucose transport activity per se. Polymyxin B (100 micrograms/mL) inhibited the insulin-stimulated uptake activity in this transport system by 22.5% while it inhibited the insulin stimulated uptake activity in intact adipocytes which were not exposed to KCN by 32.2%. These results suggest that diazoxide inhibits the function of the erythrocyte glucose transporter, GLUT1 (classified by Bell et al.), and indicate that the inhibition of the glucose transport activity recruited by insulin is the major effect of polymyxin B (100 micrograms/mL) and the inhibition of the process of insulin action is rather small. PMID- 7871974 TI - Red blood cell sorbitol in diabetic children. AB - When red blood cells (RBC) were incubated with various concentrations of glucose, the RBC sorbitol level increased in a concentration-dependent manner. The elevated RBC sorbitol level was not reduced by further incubation in a glucose free medium. In both diabetic and non-diabetic children, an increase of RBC sorbitol levels occurred in the oral glucose tolerance test and the return to baseline was delayed in diabetics compared with non-diabetics. In the majority of diabetics (87%), RBC sorbitol levels exceeded the upper limit of the normal range, which was arbitrarily determined as the mean + 2 s.d., in healthy non diabetic children and adults. A good correlation was observed between RBC sorbitol levels and plasma glucose levels (r = 0.644). In both diabetics and non diabetics, no correlation was observed between RBC sorbitol levels and age, and in diabetics the RBC sorbitol level was not related to the duration of disease. A good correlation was observed between RBC sorbitol levels, and hemoglobin Alc (HbAlc) or fructosamine levels in diabetic children. PMID- 7871975 TI - Umbilical cord blood as a rich source of immature hematopoietic stem cells. AB - To investigate immaturity of hematopoietic progenitor cells in umbilical cord blood mononuclear cells (CB-MNC), the formation of macroscopic colonies and mixed cell colonies was assayed by methylcellulose culture with various combinations of cytokines (stem cell factor [SCF], interleukin [IL]-3, IL-6, granulocyte-colony stimulating factor [G-CSF], erythropoietin [EPO]) and compared with bone marrow (BM)-MNC. Moreover, distribution of the subpopulations divided by CD34, CD38, HLA DR and CD33 was compared by flow-cytometry. Colonies derived from CB-MNC were so large that they could be observed with the naked eye and consisted of a variety of types of hematopoietic cells. Mixed-cell colonies were formed to a much greater extent in CB-MNC than in BM-MNC. Addition of EPO, IL-3, and SCF had rapid effects on the growth of mixed-cell colonies. The subpopulations of immature hematopoietic progenitor cells (CD34+, CD38-, HLA-DR-), which are supposed to be able to differentiate into hematopoietic precursors and stromal cells, were significantly higher in CB-MNC (8.7 +/- 6.6%) than in BM-MNC (0.0 +/- 0.1%; P < 0.001). These results suggest that CB is a rich source of immature hematopoietic progenitor cells compared to BM. PMID- 7871976 TI - Importance of mechanical damage to urinary red blood cells by the glomerular basement membrane. AB - The reasons for morphological changes of urinary red blood cells (RBC) in patients with glomerulonephritis are still controversial. In order to evaluate the importance of mechanical damage by the glomerular basement membrane (GBM), we examined urinary RBC taken from the patients with two different diseases which have characteristic GBM changes. Urinary RBC taken from 20 patients with Alport syndrome and nine with thin GBM disease were examined using a scanning electron microscope. Nineteen out of the 20 patients (95.0%) with Alport syndrome showed 'glomerular type', while five of the nine patients (55.6%) with thin GBM disease showed 'glomerular type'. These results suggest that more complicated GBM abnormalities cause more severe RBC distortion. Therefore, we conclude that mechanical damage by the GBM may be the major factor in dysmorphism of urinary RBC. PMID- 7871977 TI - Efficacy of captopril treatment in children with steroid-resistant nephrotic syndrome. AB - We studied the efficacy of captopril, an angiotensin-converting enzyme inhibitor in treating persistent moderate or severe proteinuria in children with various glomerular diseases other than minimal-change nephrotic syndrome. Captopril was administered for 3 months to 15 normotensive and nonazotemic or mildly azotemic patients (12 boys, 3 girls) in whom corticosteroid and cytotoxic treatment had failed to induce remission. Urinary protein excretion decreased from 2873.14 +/- 1937.50 (mean +/- s.e.m.) to 1684.71 +/- 1463.13 mg/day (P < 0.05). The reduction in proteinuria was not related to a significant fall in systemic blood pressure or a change in renal function. Serum albumin did not rise and side effects due to captopril were not observed. We concluded that, in the short term, captopril can be used safely and effectively for decreasing the proteinuria of nephrotic children unresponsive to conventional therapy. PMID- 7871978 TI - Major histocompatibility complex antigens and immune mechanisms in steroid responsive nephrotic syndrome. AB - Although the pathogenesis of steroid-responsive nephrotic syndrome (SRNS) is obscure, involvement of an immune mechanism is often suggested. Further evidence of an immune basis for this disorder is an increased frequency of specific major histocompatibility complex (MHC) antigens. In the first part of this study, the phenotypic frequency of HLA-A, -B, -C, -DR antigens were investigated in 30 children with SRNS and in 630 controls. In the second part, total T (CD3+ cells) and B lymphocytes (CD19+ cells) and the lymphocyte subsets (CD4+, CD8+ cells and their ratio) were studied in the same patients and in 30 healthy children. The investigations of all patients were performed during the acute stage and 14 of 30 during remission stage. Human leukocyte antigens (HLA) were determined by standard microlymphocytotoxicity assay and lymphocytes were analyzed by flow cytometry. Human leukocyte antigens A3, DR4, DR7 and the haplotype HLA-A2/B12 showed the strongest association with SRNS. In the studies for cellular immune disorder, CD3+ and CD8+ cells were found to be decreased significantly in the acute stage before beginning steroid therapy. No significant difference in lymphocyte subsets was observed in the remission stage without steroid or immunosuppressive therapy. PMID- 7871979 TI - Effect of corticosteroids in hereditary spherocytosis. AB - Prednisolone was administered to three children with hereditary spherocytosis. At the time corticosteroid therapy was started, two of the patients were suffering from severe hemolytic anemia and the 3rd patient had partially recovered from hemolytic anemia after splenectomy. All of the patients prednisolone produced a remarkable increase in the hemoglobin levels with a concomitant increase in reticulocyte counts. We conclude that corticosteroids might stimulate erythropoiesis and may be an alternative therapy to red cell transfusion in pre operative states for patients with hereditary spherocytosis. PMID- 7871980 TI - Effects of an acaricide on asthmatic children with house dust mite allergy. AB - D'Allergen is a recently available acaricidal and allergen reducing agent. To study any beneficial effects of treating houses with this agent in asthmatic children with dust mite allergy, histamine bronchial responsiveness was measured in 18 children before and 6-8 weeks after their homes were treated with the agent. Comparisons were with nine similar asthmatics whose homes were not treated. The mean provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 s (PC20) increased from 1.02 mg/L to 2.07 mg/L in all 18 children who were studied (1.01 doubling doses). Bronchial responsiveness was relatively unchanged in a well matched control group of nine children studied over comparable time periods (PC20 pre was 1.25 mg/L, PC20 post was 0.67 mg/L). The results suggest that treating homes with D'Allergen reduces bronchial reactivity in asthmatic residents with house dust mite allergy. PMID- 7871982 TI - Exercise performance in children with hyperthyroidism. AB - An attempt was made to define exercise performance in children with untreated hyperthyroidism using treadmill stress testing. Data were obtained for five female patients and the results were compared with those obtained for 16 normal female subjects. There were no significant differences at rest between the hyperthyroidism group and the control group in oxygen uptake, minute ventilation and respiratory rate. On the other hand, heart rate in the hyperthyroidism group was significantly higher than that in the control group. During exercise, there were significant differences between the two groups in oxygen uptake, heart rate, minute ventilation and respiratory rate. Hyperthyroid patients did not show an abrupt increase in heart rate during the first 30 s of exercise. Exercise stress testing can therefore reveal cardiopulmonary abnormalities that are not evident at rest in children with hyperthyroidism. PMID- 7871981 TI - Alternative treatment may lower the need for use of extracorporeal membrane oxygenation. AB - Access to artificial surfactant and high frequency oscillatory ventilation (HFO) in Japan seems to affect the actual indications for extracorporeal membrane oxygenation (ECMO). The relation between the methods of treatment and survival and/or neurological sequelae of 27 neonates with severe respiratory failure who would have met the US ECMO entry criteria in the Neonatal Intensive Care Unit of National Children's Hospital, Tokyo between January 1988 and May 1992 were retrospectively analyzed. Out of 27 neonates, conventional treatment including artificial surfactant was successful in 6 cases (22%). High frequency oscillatory ventilation was used for the 21 cases who did not respond to conventional treatment and it was effective in 5 cases (19% of total). Extracorporeal membrane oxygenation was used on 11 (40% of total) of 16 cases who did not respond to HFO. Eight (29% of total or 73% of ECMO cases) of these cases survived and 3 cases (11% of total) died. The remaining 5 cases (19% of total) who met the exclusion criteria of ECMO died. No patient with respiratory distress syndrome (RDS) became ill enough to meet the US ECMO entry criteria. Six out of 8 congenital diaphragmatic hernia cases were saved on a delayed surgery protocol with HFO. Only about 1% of the neonates who were admitted to our NICU during the last 4 years needed ECMO treatment. Forty-one per cent of the patients who would have met the US ECMO entry criteria were treated successfully without ECMO. The necessity for ECMO is less in Japan than in the US because other methods can often be used successfully to treat severe respiratory disorders. PMID- 7871983 TI - Circadian rhythm of blood pressure in children with reference to normal and diseased children. AB - Circadian rhythms of blood pressure in children were investigated using ambulatory blood pressure monitoring (ABPM). The subjects were 58 normal children (26 boys and 32 girls), 10 children with orthostatic dysregulation (OD) consisting of (three boys and seven girls) and 13 children taking prednisolone (nine boys and four girls). Systolic pressure in the normal group increased from early morning, peaked in the afternoon and gradually dropped thereafter. Blood pressure in the 22:00-05:30 h time range was significantly lower than in other time ranges. Blood pressure in the OD group was generally lower than in the normal group, while that in the steroid group tended to be higher. Systolic mid line estimating statistic of rhythm (MESOR) was significantly higher in boys than girls in both 10-12 year olds and 13-15 year olds according to Cosinor analysis. However, no increase in MESOR was observed in either boys or girls between the 10 12 year and 13-15 year age groups. The OD group showed lower diastolic MESOR than the normal group and the steroid group showed higher systolic MESOR. Seventy-two per cent of those in the normal group manifested significant circadian rhythm. Only 50% of 10-12 year olds manifested circadian rhythm, whereas the figure for 13-15 year olds increased to 80-90%, suggesting that a pacemaker regulating circadian rhythm comes into effect at puberty. The percentage of those who manifested circadian rhythm in the OD group and steroid group was about 60%, lower than in the normal group. PMID- 7871984 TI - A case of common variable immunodeficiency associated with cyclic thrombocytopenia. AB - A 12 year old boy was found to be deficient in immunoglobulins (Ig) A, G2 and G4, and common variable immunodeficiency was diagnosed. He also had cyclic thrombocytopenia at intervals of approximately 28-30 days. His bone marrow revealed normocellular with slightly decreased megakaryocytes. In vitro colony assays showed markedly imparied megakaryocytopoiesis, erythropoiesis and granulopoiesis. Platelet-associated IgG was elevated at his thrombocytopenic phase. Direct Coombs' test was repeatedly positive. Although not defined at present, we suggest the autoimmune nature of the disease. PMID- 7871985 TI - Bone marrow transplantation for erythroleukemia: a case report. AB - A 2 year old girl was diagnosed as having erythroleukemia (EL; M6 according to the French-American-British classification). After one course of low-dose cytosine arabinoside (Ara-C), complete remission was obtained. After three courses of low-dose Ara-C for consolidation, allogeneic bone marrow transplantation was performed from HLA-identical sibling. The course of post transplantation was uneventful. Two years after transplantation, she continues to have durable engraftment and remission. In children with EL, conventional chemotherapy appears to be inadequate for producing durable long-term disease free survival. Bone marrow transplantation should be considered in children with EL, in cases where suitable donors are available. PMID- 7871986 TI - Agnogenic myeloid metaplasia in childhood: a report of two cases and efficiency of intravenous high dose methylprednisolone treatment. AB - Myelofibrosis with myeloid metaplasia, or agnogenic myeloid metaplasia (AMM) is a chronic myeloproliferative disorder characterized by fibrosis of the bone marrow accompanied by aniso- and poikilocytosis, leukoerythroblastosis and hepatosplenomegaly with extramedullary hematopoiesis. Agnogenic myeloid metaplasia is very rare in children. In this report, two cases of AMM in whom the onset of the illness were at 3 and 12 months of age, are presented. Both had severe anemia, hepatosplenomegaly and bone marrow fibrosis. Lymph node biopsy of the first patient and liver biopsy of the second revealed extramedullary hematopoiesis. They were treated with an intravenous high dose of methylprednisolone (daily 30 mg/kg for 3 days, 20 mg/kg for 4 days, 10 mg/kg for 1 week, 5 mg/kg for 1 week). A complete improvement of hematological and clinical findings was observed. PMID- 7871987 TI - Minocycline-induced hemolytic anemia. AB - A case of drug-induced immune hemolytic anemia is described. A 2 year old boy exhibited sudden anemia and hemoglobinuria after administration of minocycline (MINO). The specific immunoglobulin G antibody against MINO was demonstrated in the patient's serum by western blotting. This is a rare example where anti minocycline immune complex-mediated hemolysis was responsible for an intravascular hemolytic process. PMID- 7871988 TI - Twins with moyamoya disease. AB - Moyamoya disease is a progressive disease which involves the internal carotid arteries and its branches bilaterally. The disease is reported both in adults and in children. Moyamoya disease is frequently seen in Japanese patients having certain human leucocyte antigen (HLA) haplotypes including HLA-Aw24, Bw46 and Bw54. Twin cases are rarely reported in the literature. We hereby present the first Turkish monozygotic twins with moyamoya disease whose HLA haplotypes are A2, A9, B21, Bw22, Bw4, Bw6, Cw3, and DR2, DR4, DRw52, DRw53, Dq7. The patients with advanced disease were given nifedipine and intravenous immunoglobulin (400mg/kg/d for 5 days). During the 11 months of follow-up, the patients were attack free. PMID- 7871989 TI - Consecutive cerebral MRI findings of acute relapsing disseminated encephalomyelitis. AB - A seven year old girl with acute relapsing disseminated encephalomyelitis (ARDEM) was observed with serial magnetic resonance imaging (MRI) examination. She had the first encephalomyelitis episode at the age of 2 years 9 months. She entered remission with steroid therapy. She suffered a recurrence at the age of 7. Steroid therapy was instituted and consecutive magnetic resonance imaging (MRI) was performed. In spite of rapid improvement of neurological abnormality with steroid and steroid pulse therapy, disseminated high intensity lesions in T2 weighted imaging which were considered as demyelination remained for a long time. Magnetic resonance imaging seems to be most suitable for evaluating the clinical condition and long-term follow-up of ARDEM. PMID- 7871990 TI - Kawasaki disease with a concomitant primary Epstein-Barr virus infection. AB - A two year old boy exhibited not only clinical manifestations which suggested a recurrence of Kawasaki disease (KD) but also evidence of a primary infection by Epstein-Barr virus (EBV) including tonsillitis, splenomegaly and atypical lymphocytosis in the peripheral blood. An inverted CD4/CD8 ratio in lymphocyte subsets suggested the presence of infectious mononucleosis (IM). Epstein-Barr virus titers (viral capsid antigen-immunoglobulin G 1:20; Epstein-Barr virus associated nuclear antigen < 1:10) showed an acute EBV infection and the presence of EBV genome in the blood was determined by the polymerase chain reaction technique. In Japan, the peak incidence of KD and IM is in children under 4 years of age. From the investigation of EBV titers, it has been reported that some patients with KD develop an associated, unusual primary EBV infection. Kawasaki disease concurrent with a primary EBV infection as in this case, suggests the possibility of an etiologic agent related to the KD rather than to the EBV infection itself. PMID- 7871991 TI - Early onset of cecal perforation in neonatal, recto-sigmoid type Hirschsprung's disease. AB - Hirschsprung's disease has been considered to cause intestinal perforation in rare cases. Even if a perforation occurs, the majority of cases are associated with the long-segment or total colonic type. Our case developed the perforation in the neonatal period in spite of being of the recto-sigmoidal type, and it affected the cecum. We do not have a good explanation for this condition. However, the pathological examination of the specimens of the perforated cecum revealed some necrosis (ulceration, subcutaneous hemorrhage, congestion and severe edema) which was considered to be caused by ischemia, secondary to a localized vascular accident in the wall of the distended intestine. PMID- 7871992 TI - Idiopathic infantile hypercalcemia discovered in the newborn period. AB - We report a male newborn with typical clinical signs of idiopathic infantile hypercalcemia (IIH); that is, hypercalcemia, hypercalciuria, an elfin face and nephrocalcinosis without giving Vitamin D3 supplementation to the patient. He had been treated with a vitamin D-free, low calcium milk and rectal administration of exogenous calcitonin (elcatonin). The latter seemed to be more effective as a treatment for IIH. The serum calcium level came within the normal range and the serum 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) level decreased from 101.5 to 75.6 pg/mL with the treatments mentioned above. These results suggest that a high serum concentration of 1,25(OH)2D3 is part of the pathogenesis of IIH. However, we were not able to clarify the pathogenesis of the high serum concentration of 1,25(OH)2D3. PMID- 7871993 TI - Kabuki make-up syndrome associated with chronic idiopathic thrombocytopenic purpura. AB - Although susceptibility to infections in Kabuki make-up syndrome (KMS) has frequently been reported, there have been few immunological studies. We describe a 14 year old girl with KMS exhibiting chronic idiopathic thrombocytopenic purpura (chronic ITP), including immunological studies. Corticosteroid therapy was not effective therefore splenectomy was performed. The patient's platelet count increased transiently. Immunological studies revealed normal T cell functions and low serum immunoglobulin A (IgA) levels. Because of the abnormalities of B cell functions in chronic ITP and low serum IgA levels in our patient, we speculate that there may be some abnormalities of humoral immunity in KMS. PMID- 7871994 TI - Increased cerebrospinal fluid levels of histamine in children with aseptic meningitis. PMID- 7871995 TI - [Effect of AMG-1 on free intrasynaptosome calcium level and on the isolated artery contraction induced by norepinephrine]. AB - Recently, the intracellular free calcium overload has been considered as an important factor in the development of ischemic brain damage. In this paper, the effect of AMG-1 on free calcium concentration ([Ca2+]i) in rat intrasynaptosome and on the isolated rat tail artery contraction induced by norepinephrine (NE) were studied by using Fura-2 fluorescence technique and contraction force measurement, respectively. The results show that: 1. AMG-1 10 mumol.L-1 and 100 mumol.L-1 reduced the KCl induced [Ca2+]i increase by 19 +/- 11% and 57 +/- 12%. 2. AMG-1 100 mumol.L-1 markedly decreased the NE-dependent intracellular calcium induced contraction force (43 +/- 11%). In our previous study, AMG-1 was shown to have improving effect on ischemic damage following middle cerebral artery occlusion in rats. On the basis of these results, we suggest that the mechanism of AMG-1 in improving cerebral ischemic damage may be due to the decrease of [Ca2+]i. PMID- 7871996 TI - [Effect of glycyrrhetinic acid on DNA damage and unscheduled DNA synthesis induced by benzo (a) pyrene]. AB - Glycyrrhetinic acid (GA) is an active component of Glycyrrhiza uralensis Fisch. In this study, the effects of glycyrrhetinic acid on DNA damage and unscheduled DNA synthesis induced by benzo (alpha) pyrene were studied. Mouse ear edema was visible obviously at the 6th h after topical application of single dose croton oil. A topical application of croton oil on the back of ICR mice for 5 h, induced elevation of ornithine decarboxylase (ODC) activity in epidermal. The administration of glycyrrhetinic acid (50-200 mg.kg-1.d-1) to animals for 3 days exhibited 20%-80% inhibition of epidermal ornithine decarboxylase activity in a dose-dependent manner. Benzo (alpha) pyrene obviously caused DNA damage and unscheduled DNA synthesis mediated by S9 fraction in Chinese hamster lung cell line. Glycyrrhetinic acid was found to protect the rapid DNA damage induced by benzo (alpha) pyrene. At concentration of 5 micrograms.ml-1, glycyrrhetinic acid exhibited 70% protection. At 20 micrograms.ml-1, this action was more potent and approached to 80%. The addition of hydroxyurea 10 mmol.L-1 suppressed DNA replicative synthesis to 84.04% and benzo (alpha) pyrene stimulated the DNA repair synthesis (6-fold). Glycyrrhetinic acid (20 micrograms.ml-1 and 50 micrograms.ml-1 significantly decreased the stimulation of DNA repair synthesis induced by benzo (alpha) pyrene. This suggests that glycyrrhetinic acid has effective anti-initiating and anti-promoting activities and could be used for cancer chemopreventive purpose. PMID- 7871997 TI - Determination of fluconazole by direct injection of plasma and high performance liquid chromatography with column switching. AB - High performance liquid chromatography with column switching has been developed for the determination of fluconazole in plasma. The plasma samples were injected onto a precolumn packed with LiChromprep RP2(25-40 microns) after simple dilution with a solution of 0.2 mol.L-1 acetic acid. Distilled water was used to wash out protein and other polar components in plasma. After switching, the concentrated fluconazole was eluted in the back-flush mode onto a Shimpack CLC-ODS column with methanol--0.2 mol.L-1 ammonium acetate (pH 2.7) (50:50) as mobile phase. Purge solutions were used for clean-up and for regenerating the precolumn. The method showed a good precision and excellent recovery. The detection limit was 0.12 micrograms.ml-1 plasma. The RSD's (intra- and interday) were less than 6.3%. The method has been successfully used to determine bioavailability and pharmacokinetics of fluconazole in Chinese volunteers. PMID- 7871998 TI - [Quantitative analysis of bencynonate in human plasma using a deuterated internal standard by GC-MS/SIM]. AB - Bencynonate is a newly developed anticholinergic drug. After a dose (2 mg/person or 4 mg/person) of bencynonate, the circulating concentrations are so low that therapeutic drug monitoring studies have previously been impossible. Radioisotope assay and radioaccepter assay had been used in rat experiments, but the detections limits of these methods were not sensitive enough for the therapeutic drug monitoring. Further, the two methods were unsuitable in the human. For evaluation of the pharmacokinetics and the relative bioavailability of bencynonate in man, a gas chromatographic--mass spectrometric method for quantitative analysis of bencynonate in human plasma was developed. Deuterated bencynonate served as the internal standard and selected-ion monitoring of the fragments of bencynonate and internal standard permitted the quantitation of bencynonate down to 25 pg.ml-1 of plasma. The linearity was in the range from 25 pg.ml-1 to 3 ng.ml-1 of bencynonate plasma concentration. At 0.25 ng.ml-1 level the recovery and relative standard deviation of variation are 54.3% and 19.1%, respectively. Application of the method to clinical studies gave the results of pharmacokinetics and relative bioavailability of bencynonate in man. PMID- 7871999 TI - [Effects of tripchlorolide (T4) of Tripterygium wilfordii hook on the production of prostaglandin E2 by synovial cells of rheumatoid arthritis]. AB - The effects of tripchlorolide, an active ingredient (T4) of Tripterygium wilfordii Hook on the production of prostaglandin E2(PGE2) by synovial cells of rheumatoid arthritis (RA) patients were investigated. Six cases of definite RA (female 5, male 1, mean age 45 with an average course of disease of 9 years) were selected. Surgically obtained synovium specimen were dissociated into digested synovial single cells (DSSC). The cells were incubated with various concentrations of T4 for 48 hours. Using radioimmunoassay T4 was found to significantly inhibit the production of PGE2 (control 6.10 +/- 2.30 vs T4 treated 0.58 +/- 0.47 x 10(-5) mol.L-1) by short-term cultured DSSC of RA patients. The results of this study suggests that T4 may be useful in the forthcoming treatment of RA due to its inhibition of production of PGE2 by synovial cells. PMID- 7872000 TI - Estimation of lactate release from contracting muscles in humans: a response to recent correspondence. PMID- 7872001 TI - Dorsal column inhibition of nociceptive thalamic cells mediated by gamma aminobutyric acid mechanisms in the cat. AB - Cells in posterior parts of the cat thalamus were investigated. Responses in single units excited by electrical stimulation in the lateral funiculus (LF), the dorsal column nucleus (DCN) or the canine tooth pulp (TP) were analysed. All cells had a spontaneous resting activity which could be increased by extracellular iontophoretic application of DL-homocysteic acid (DLH) and decreased by gamma-aminobutyric acid (GABA). No effect on the spontaneous firing rate was observed following iontophoresis of the selective GABA-antagonists, picrotoxin (GABA-A receptor antagonist) or saclofen (GABA-B receptor antagonist). However, the decreased firing following GABA application was partially blocked by picrotoxin but not by saclofen. A phasic inhibition induced by DCN stimulation in nociceptive thalamic cells is indicated since simultaneous administration of picrotoxin increased the evoked response. This type of inhibitory mechanism could not be detected following LF or TP stimulation. The extracellular activity evoked by electrical stimulation of LF or TP was significantly depressed by preceding electrical stimulation in the DCN. This inhibition was reversed by simultaneous administration of picrotoxin, indicating an involvement of GABA-A receptors. The reversal of the DCN-induced depression of the late responses following LF stimulation occurred after application of saclofen. It is suggested that this effect is partly mediated via GABA-B receptors. Results from the present study indicate an interaction in the thalamus between presumed low-threshold (DCN) and presumed nociceptive afferents (LF and TP) similar to that previously described in the spinal cord. PMID- 7872002 TI - Human sympathetic nerve activity to glabrous skin does not increase during simulated diving. AB - In humans, cardiovascular adjustment to simulated diving causes a marked increase in sympathetic outflow to intramuscular vessels and muscle vasoconstriction. Skin vasoconstriction in the hand also occurs during diving in humans. Skin nerve sympathetic activity (SSA), containing vasoconstrictor signals to glabrous skin, unexpectedly was reduced during diving in a previous study of SSA recorded in the peroneal nerve. SSA was recorded by microneurography in the median nerve in 13 healthy volunteers during simulated diving. Skin blood flow in the hand and one finger was monitored. The typical SSA response, irrespective of duration of diving and water temperature, was an increase during the control period immediately prior to immersion of the face and a sudden reduction of SSA when the face was immersed. The increase in SSA preceding the dive was accompanied by vasoconstriction, which continued during the dive, but re-dilation regularly occurred before the end of the dive. Inhibition of SSA was not total. Mental arithmetic during diving evoked strong bursts of SSA, similar to those seen normally during mental stress. It is concluded that the true response of SSA to simulated diving is an inhibition of the immediately preceding outflow, in agreement with observations of cutaneous blood flow in animals. The skin vasoconstriction recorded during simulated diving is a consequence of an SSA increase before the procedure, suggested to be a stress response before the forthcoming manoeuvre. The SSA response during simulated diving is the opposite to that of sympathetic outflow to muscle, which emphasizes the diversity of sympathetic regulation of different organ systems. PMID- 7872003 TI - Is palmar and plantar sweating thermoregulatory? AB - We tested the hypothesis that palmar and plantar sweating has a thermoregulatory role and is mediated by the same thermoregulatory mechanisms that control sweating in the rest of the body surface. In a series of empirical tests involving 34 participants (five of whom exhibited palmar hyperhydrosis), the effect of high environmental temperature on sweating was examined. Wilcott's finding, that effects at the palm are of considerable magnitude, was confirmed only in subjects who were in a state of excitement. In relaxed subjects, the effects of high environmental temperature on palmar and plantar sweating was negligible. We conclude that the palms and soles do not directly participate in thermoregulation. PMID- 7872004 TI - Intramuscular pressure, torque and swelling for the exercise-induced sore vastus lateralis muscle. AB - This study investigated changes in intramuscular fluid pressure (IMP), torque and swelling related to delayed onset muscle soreness (DOMS) of the vastus lateralis muscle. IMP was measured via catheterization in the unstretched (0 degree, full extension) and stretched (90 degrees of knee flexion) muscle at rest; then IMP and knee extension torque were determined during maximal contractions pre and 2 d after (post) repetitive eccentric activity in one leg for eight male subjects. DOMS of the vastus lateralis muscle was associated with a significant elevation in IMP at rest as indicated by pre (0 degree: 5.4 mmHg, 90 degrees: 80 mmHg) and post (0 degree: 8.4 mmHg, 90 degrees: 13.2 mmHg) comparisons (P = 0.02). Soreness symptoms were aggravated when the muscle was stretched and this was accompanied by a significantly higher post IMP at 90 degrees vs. 0 degree (P = 0.01). During maximal contractions, peak torque declined by 15% relative to pre and peak IMP declined by 26%; DOMS symptoms, however, were most severe during this manoeuvre. Biopsies from the sore vastus lateralis muscle revealed significantly larger fibre areas for all fibre types as compared with contralateral controls (P < 0.01); however, no differences were detected for extracellular volume percent comparisons. This study shows that DOMS of the vastus lateralis muscle is associated with extensive intracellular swelling and with elevated IMP. In line with previous studies, fibre swelling may be a common subsequence to repetitive eccentric activity; the ability of IMP measurements to detect this swelling at rest and during various manoeuvres for other muscles may depend on compartmental compliance. PMID- 7872005 TI - Reduced oxygen availability during high intensity intermittent exercise impairs performance. AB - This study examined the influence of reduced oxygen availability on the ability to perform repeated bouts of high intensity exercise on a cycle ergometer. Seven male physical education students performed 10 exercise bouts (of 6 s each), interspersed with 30-s recovery periods, under hypoxic and normoxic conditions. The hypoxic condition was carried out in a low pressure chamber at 526 mmHg. Subjects were instructed to try to maintain a target pedalling speed of 140 rev min-1 during each exercise period. The mean power output of the first exercise bout was approximately 950 W. In both experimental conditions, all subjects were able to maintain the target speed for the first 3 s of each of the 10 exercise bouts. During the last 3-s interval of each exercise period the target speed was not maintained in both conditions over the 10 sprints. However, the reduction was greater in the hypoxic condition (P < 0.05). Post-exercise blood lactate accumulation was higher with hypoxia [10.3 (0.7) vs. 8.5 (0.8) mmol l-1, P < 0.05]. Oxygen uptake, measured during the exercise and recovery periods of sprints 6-9, was lower in the hypoxic condition [3.03 (0.2) vs. 3.19 (0.2) 1 min 1, P < 0.05]. These results indicate that a reduction in oxygen availability during high intensity intermittent exercise results in a higher accumulation of blood lactate and a lower oxygen uptake. The ability to maintain a high power output is impaired. PMID- 7872006 TI - Potentiation of concentric plantar flexion torque following eccentric and isometric muscle actions. AB - In a stretch-shortening cycle (SSC) the concentric muscle action is enhanced by a preceding eccentric muscle action. The hypothesis of the present study is that a preceding isometric action can also have an effect on a following concentric action, but to a lesser degree. A KINetic-COMmunicator II dynamometer was used to test muscle strength of the plantar flexion of the right foot in 20 healthy women. Maximal voluntary torque measurements were made at different angular velocities (120 degrees s-1 and 240 degrees s-1) and the range of motion of the ankle joint was 78-125 degrees. The assessment was based on concentric torque output and EMG recording from the gastrocnemius muscle under three different types of testing conditions (concentric actions with and without preceding eccentric or isometric actions, all with maximal efforts). The results showed that preceding muscle actions led to greater concentric torque output (P < 0.01) between 90 and 99 degrees plantar flexion. However, the increase in the concentric action was significantly (P < 0.01) larger with eccentric than with isometric preceding action, regardless of velocity. The EMG activity of the concentric action showed unchanged or lower values when preceded by a muscle action. In this model our conclusion is that the main reason for larger concentric torque values after a preceding muscle action is that time is sufficient for maximal muscle tension development; in addition, elastic energy is stored, particularly during the preceding eccentric action. Our results show that the effect of preceding muscle actions should be taken into account when measuring isokinetic muscle strength at relatively small angular movements. PMID- 7872007 TI - Sprint-training effects on some contractile properties of single skinned human muscle fibres. AB - The effects of sprint training on the contractile properties of human muscle fibres obtained by needle biopsy were investigated. Individual fibres were mechanically skinned and activated by Ca(2+)- and Sr(2+)-buffered solutions at pH 7.1, and allocated to distinct populations on the basis of their contractile characteristics. The majority of fibres sampled pre-training could be separated into the three major fibre groups: Populations I (24/70, 34%), II (25/70, 36%) and III (18/70, 26%), which exhibited characteristics similar to those of histochemically classified type I, IIA and IIB fibres, respectively. The remainder (3/70, 4%) represented another fibre group, with intermediate characteristics. The muscle fibres were also activated by Ca2+ at a reduced pH of 6.6, to mimic the intracellular acidification that occurs during intense exercise. Lowering pH increased the threshold for contraction by Ca2+, reduced Ca2+ sensitivity, and increased the steepness of the force-pCa relationship, in all fibres sampled from the three major fibre groups. Maximum force was not significantly reduced in any fibre population. In the post-training sample, the three major fibre types were present in different proportions: Populations I (10/52, 19%), II (20/52, 38.5%) and III (11/52, 21%). Three other fibre groups sampled in low numbers exhibited contractile characteristics intermediate between Population I and Population II. Following sprint training all of the three main fibre populations exhibited higher thresholds for contraction by, and lower sensitivities to, Sr2+ but not Ca2+, compared with the fibres sampled pre training. Maximum force was significantly lower in Population II fibres after sprint training. At pH 6.6, post-trained Population III fibres exhibited even lower Ca2+ sensitivity, with concomitant increases in the threshold for contraction and force-pCa curve steepness. PMID- 7872008 TI - Effect of ageing on ultrastructure of slow and fast skeletal muscle tendon in rabbit Achilles tendons. AB - This reports presents the changing morphological characteristics of collagen and fibroblasts in the soleus and gastrocnemius muscle tendon of female Japanese white rabbits with ageing. The fibroblasts decreased in number per 37 microns 2 with ageing in each group, and their morphology became longer and more slender through ageing. The mean fibril area and diameter of the collagen fibrils of soleus muscle tendon (SMT) and lateral gastrocnemius muscle tendon (GMT) in 8- to 10-month old rabbits were significantly higher than those of 3-wk-old rabbits during growth (P < 0.01). The mean area and diameter of collagen fibrils of SMT and GMT decreased during senescence: the values for 4- to 5-yr-old rabbits were lower than those for 8- to 10-month-old rabbits, but the difference was not significant. Statistically significant differences in fibril area and diameter between the SMT and GMT were not found during ageing. The number of thick fibrils increased during growth, but decreased in senescence. There were more thin fibrils (30-60 nm) in the 3-wk-old rabbits than in the 8- to 10-month old and 4 to 5-yr-old groups, and the large-diameter collagen (300-360 nm) was more abundant in the 8- to 10-month-old group than in the 3-wk-old and 4- to 5-yr-old groups. Differences in fibril size between slow and fast muscle tendons were not observed during ageing. PMID- 7872009 TI - Cerebral osmoregulatory reduction of plasma renin concentration in sheep. AB - A centrally mediated inhibitory influence of plasma hypertonicity on renin secretion was investigated in conscious, Na-depleted sheep. Infusions of hypertonic solutions were made into the carotid artery or jugular vein, and the effects on plasma renin concentration (PRC) compared. Intracarotid infusion of 1.65 M NaCl significantly reduced PRC (to 74% of the pre-infusion value) within 15 min of the commencement of the infusion whereas corresponding intrajugular infusion did not. Intracarotid infusion of 3 M sorbitol for 45 min also reduced PRC (to 64% of the pre-infusion level) significantly after 15 min of infusion. By contrast, neither intrajugular infusion of 3 M sorbitol, nor intracarotid infusion of isotonic 0.15 M NaCl for 45 min significantly reduced PRC. Intracarotid infusion of hypertonic sorbitol for 45 min did not inhibit PRC in sheep with cerebral lesions of the lamina terminalis. These results show that plasma hypertonicity may have an inhibitory influence on renin secretion. The inhibition is probably mediated by an effect of hypertonicity on the CNS, rather than a direct effect on the kidney. PMID- 7872010 TI - Remodelling of the retinal arterioles in descending optic atrophy follows the principle of minimum work. AB - Mathematical modelling indicates that the minimum energy cost for blood flow is achieved when the arteries are arranged in a branching hierarchy such that the radii of the vessels are adjusted to the cube root of the volumetric flow (principle of minimum work). This is known to apply over several magnitudes of vessel calibres, and in many different organs, including the brain, in humans and in animals. This paper addresses the issue of remodelling of one and the same arterial network to long-term changes in blood flow. This has not been studied previously in humans. We measured the radius of parent (r0) and branch segments (r1 and r2) of the retinal arteriolar network in fundus photographs of six patients with blinding, non-vascular retrobulbar optic nerve lesions, mostly traumatic in origin, before and after the development of descending optic atrophy. Attenuation of retinal arterioles is a well-known phenomenon in descending optic atrophy, and is attributable to decreased metabolic demand secondary to loss of the retinal ganglion cells and their axons. On average, arteriolar diameters decreased by 15.2 +/- 17.7% (SD), with 95% confidence intervals of 18.7% and 11.7%; the radii decreased significantly (P = 0.0001) (n = 99). The area ratio of the bifurcations, defined as (r2(1) + r2(2))r-2(0), was 1.23 +/- 0.2 before, and 1.18 +/- 0.2 after optic atrophy (n = 36); the change of area ratio was not significant. The branching geometry of the retinal arteriolar network obeyed strictly the optimum branching rule of the principle of minimum work, or r3(0) = r3(1) + r3(2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872011 TI - Further evidence of increased motor cortex excitability during tonic plantar flexion in humans. PMID- 7872012 TI - Nimodipine-resistant tone in myogenically active preglomerular arteries of rat kidneys. PMID- 7872013 TI - Delayed treatment with the spin trap alpha-phenyl-N-tert-butyl nitrone (PBN) reduces infarct size following transient middle cerebral artery occlusion in rats. PMID- 7872014 TI - Chromatographic analysis (TLC) aprindine and nadoxolol in human plasma. AB - Aprindine and nadoxolol extracted from plasma were separated by TLC method on silica gel by ascending technique on 5 x 20 cm and 2.5 x 7.5 cm microscopic slides and also by horizontal development, using suitable mobile phases. The substances were identified by reaction with Kiefer reagent (up to the amount 100 ng of aprindine and 300 ng of nadoxolol). PMID- 7872015 TI - The protective role of pyridine N-oxide in cytotoxicity and genotoxicity of hydrogen peroxide and adriamycin. AB - Scavenging and cytotoxic activity of pyridine N-oxide was investigated in cultured V3 and CHO cells. Pyridine N-oxide was effective in suppressing the cytotoxic effects induced in these systems both by hydrogen peroxide and adriamycin and preventing the production of chromosomal aberrations by these compounds. On the other hand superoxide dismutase inhibited the cytotoxic activity of pyridine N-oxide. PMID- 7872016 TI - Synthesis of new derivatives of 4-acylquinoxalin-2-ones with potential pharmacological activity. AB - Some of new derivatives of 4-acylquinoxalin-2-one obtained in the reaction of N,N'-bis(chloroacetyl)-4,5-dimethyl-o-phenylenediamine with primary amines are described. Compounds were tested for their anti-HIV activity and as ligands for 99mTc. PMID- 7872017 TI - Carboxylic esters derivatives of 2-thioxo-1H-2,3,4,5-tetrahydropyrido-[2,3-e] 1,3,4-triazepin-5-ones and 2-thioxo-1H-2,3,4,5-tetrahydro-1,3,4-benzotriazepin-5 ones. AB - 2-Thioxo-1H-2,3,4,5-tetrahydropyrido[2,3-e]-1,3,4-triazep in -5-ones [I] and 2 thioxo-1H-2,3,4,-5-tetrahydro-1,3,4-benzotriazepin-5-ones [V] furnish with methyl, ethyl and phenyl chloroformates two series of the corresponding 3-methoxy , ethoxy- and phenoxycarbonyl triazepines. In the pharmacological screening, compounds [I], [V] and [II] showed an antianxiety activity in the four plate test, compounds [II] and [III] inhibited the 5-HTP- induced head twitches, and compound [VI] showed an analgesic activity in the "writing" test. The replacement of the benzene ring by the pyridine one in triazepines is accompanied by the enhancement of anxiolytic activity as well as toxicity. PMID- 7872018 TI - Synthesis of pyridylethenyl derivatives of 3H-pyrido[2,3-d]-pyrimidyn-4-on of expected depressive activity on central nervous system. Part I. AB - Synthesis of 2-(pyridylethenyl) derivatives of 3H-pyrido[2,3-d]pyrimidin-4-on [Va k] by condensation of selected 2-methyl-3H-pyrido[2,3-d]pyrimidin-4-ones [IVa-k] with nicotinic aldehyde is described. Compounds [Vh] and [Vi] showed weak analgetic activities. PMID- 7872019 TI - Effect of experimental hyperlipidemia on the pharmacokinetics of digoxin. AB - The study was carried out on 18 male rabbits randomaly ascribed into two groups: control one on standard diet and experimental one on high-fat diet for 2 months. Pharmacokinetic assays were performed in all animals after 2 months of the experiment. Blood was sampled within 24 hours after intragastrical administration of digoxin at a dose 0.02 mg/kg. The two compartment open model for extravascular administration was used for calculations. Marked increase in plasma drug concentration, as well as decrease in total clearance were noted. The study revealed the influence of experimental hyperlipidemia on digoxin pharmacokinetics leading to a slower drug elimination. PMID- 7872020 TI - Acute and chronic toxicity of "Polfa" perphenazine. AB - The toxicity of "Polfa" perphenazine and its profile of pharmacological properties were estimated. LD50 values calculated in rats were 2000 mg/kg and 325 mg/kg, after p.o. and i.p. administration respectively. Chronic toxicity of the perphenazine was evaluated during the period of 3 month of the drug treatment p.o. or i.p. in the rats and mice. Decrease of the locomotor activity of perphenazine was observed after the highest dose (15 mg/kg) of the drug, only in the first weeks of the experiment. Also the cataleptogenic effect of perphenazine observed in the mice was diminished during 3 month of the experiment. Moreover, perphenazine did not induced significant changes in the blood morphology and histology of the internal organs. PMID- 7872021 TI - [40 years later]. PMID- 7872022 TI - [40 years of Acta]. PMID- 7872023 TI - [Sexuality and schizophrenia]. AB - The sex behaviour of patients suffering from schizophrenia has been largely overlooked. This study is aimed at describing the pattern of sexual responses and conducts in 113 inpatients with schizophrenia (DSM-III-R). A high rate of sexual dysfunction was found in both males (62.9%) and females (50%). These rates are higher than found in other previous studies. The possible cause factors of sexual dysfunctions in this group of patients and the methodological problems related to this type of study are reviewed. PMID- 7872024 TI - [Coenzyme Q 10 in psychiatry]. AB - The incidence of coenzyme Q 10 and its alterations in psychiatrical pathology is studied. A screening of a randomly selected 113-patient sample showed a high percentage of deficiencies: When taken care of, an improvement in patients' clinical pictures, with no secondary complaint could be observed. Results do not yield alteration specificity according to diagnosis. In those cases where values higher than admitted as normal were detected, neither a common symptoms nor the predomination of a determined pathology could be found. PMID- 7872025 TI - [Psychopathology of depressive mood]. AB - The distinct quality of depressed mood is a clinical sign that has been recently excluded from both the DSM-III-R, and ICD-10 diseases classification manuals. An introduction to the depressive mood concept is carried out through a review of classical psychiatric texts, concluding that depressed mood elimination from the current, operative diagnostic criteria is most unfortunate indeed. PMID- 7872026 TI - [Demographic study of obsessive compulsive disorder]. AB - This study used a large, obsessive- compulsive disorder (OCD) population (N = 157) without comorbidity, and compared them to the general population of the States of New York on the following demographic variables: sex ratio, age of onset, age first seen, marital status, occupation, birth trauma, substance abuse, religion, past psychiatric treatment, and parents' psychiatric history. A 1: 1 sex ratio with a significant gender difference was found for age of onset (females = 20.8; males = 16.3 years), and for age first seen (females = 26.4; males 20.3 years). Other significant findings were the following: More single male OCD patients, fewer widowed female patients, more white-collar workers, less drug abusers, more alcohol abstainers, and less non-problem drinkers as compared to the general population. Significantly also, more atheist/agnostic OCD patients were found as compared to other patients. For the first time, the findings can be evaluated against a comparative group. PMID- 7872027 TI - [Connotative affective perception of self concept and its link with school performance]. AB - The association between the two major Eysenckian Personality dimensions, and the affective-connotative evaluation of self-concept as a reflection of academic success/failure are analyzed among a 111-schoolchild sample. Findings show the main effect of academic performance and personality on children's affective perception of their self-concepts: Schoolchildren with a good performance enjoy a better self-appraisal, and their affective connotations are more positive than their peers' with a poorer performance. On the other hand, association between affect intensity and Neuroticism predisposition is not so clear. A relationship between neuroticism and negative affect predisposition is observed only when associated to introversion and poor performance. PMID- 7872028 TI - [Alcohol and drug consumption by adolescents in Buenos Aires]. AB - In a group of 4800 young man--sample--who were called on to the Military Service Medical Examination in 1992, was investigated the legal and illegal psychoactive drugs using in. Findings show that: a) 42% were alcohol abusers during last 30 days; b) more than 17% have used marihuana once in their lives; c) 9.7% have used cocaine and d) 1 of each 10 have recognized use psychoactive drugs without medical prescription. Cultural practices linked to excessive alcohol abuse and the present increase use of other psychoactive drugs by young people are discussed. PMID- 7872029 TI - [Sexual models in adolescents and adults]. AB - Findings of a research that has been carried over among 13- to 19-year-old young people, their parents, and their teachers with regard to sex models of all involved are presented. Subjects were from the city of Buenos Aires, Argentina. Social representations of the three subject samples involved about sex behavior, certain values linked to sexuality, and certain gender patterns are discussed. PMID- 7872030 TI - [Central American seminars for young psychiatrists of the region and training of leaders in community mental health. Sweden/PAHO-WHO collaboration program]. AB - The Swedish Psychiatric Association, in collaboration with the Department of Psychiatry, University of Umea, Sweden, and the Pan American Health Organization/WHO, has obtained economic support from the Swedish Agency for International Development (ASDI), to organize training seminars for young psychiatrists from Central America. The program will continue until 1995 with an option to pursue further studies leading to a master or other post-graduate degrees. The overall purpose is to strengthen the knowledge in epidemiology and community mental health, along the lines set by the "Caracas Declaration" of a cadre of young leaders in the field of psychiatry in Central America. PMID- 7872031 TI - [The myth of the good savage]. AB - The conquest of the New World gave way to the myth of the Good Savage. For the Renaissance intellectuals, the ancient ideas about the Golden Age (an ideal society promising an unending bliss) seemed to be brought back to life at last. Sharply contrasting with the European exacerbated unrest of the time, America stood for a redeeming hope, a symbol of a better future. The myth of the Good Savage assumes people to be naturally good, but civilization has led them into the realm of violence, hatred, and cruelty. Besides being naturally good, nice minded people, "good savages" were also useful, obedient people, most likely to be easily exploited by Europeans--a source for the historical drama to come. On the verge of freeing itself from the Spanish rule, Latin America--fighting its way toward independence, had three enlightened mentors: Voltaire, Rousseau, and Montesquieu. There, again, another deep contrast arose between the abstract characteristics of Latin American aims to perfection, and people's actual behaviors. The former "good savage" became the modern "Latin American" embodying an utopia as well as a hope in his eagerness for setting up a plural, and humanized culture. The myth of the Good Savage represents a deep longing for an objectivation of the ego-ideal: it has been used, so to speak, in collective mobilizations as well as dogmatic crystallizations, to escape from ignominous realities or to project alternatives for a better socially-shared life. PMID- 7872032 TI - [The future of psychiatry]. PMID- 7872033 TI - Serum-soluble interleukin-2 receptors in neuroleptic-naive schizophrenic subjects and in medicated schizophrenic subjects with and without tardive dyskinesia. AB - There is a growing body of literature suggesting that some schizophrenic subjects have evidence of immune activation. One marker that has been consistently elevated in studies is the serum-soluble interleukin-2 receptor (SIL-2R). This article reports the results of 2 experiments: the first compares concentrations of serum SIL-2R in neuroleptic-naive schizophrenic patients and matched controls, and the second study contrasts serum SIL-2R concentrations in medicated schizophrenic subjects with and without tardive dyskinesia. Serum SIL-2R concentrations were elevated in neuroleptic-naive schizophrenic subjects as compared with controls (1705.7 (SD 1124.2) U/ml vs 739.8 (SD 325.5) U/ml). Medicated subjects with tardive dyskinesia had increased serum SIL-2R levels (2385.5 (SD 1822.0) U/ml) compared with medicated subjects without tardive dyskinesia (1259.6 (SD 1365.3) U/ml). Thus, elevations in serum SIL-2R levels are present prior to neuroleptic treatment, and there may be an association between serum SIL-2Rs and tardive dyskinesia. PMID- 7872034 TI - Biological correlates of deliberate self-harm behaviour: a study of electroencephalographic, biochemical and psychological variables in parasuicide. AB - Clinical, electroencephalographic and biochemical variables were measured in 40 patients who attempted suicide and 27 age-matched controls. Patients had significantly higher scores for depression, hopelessness, neuroticism and psychoticism and lower scores for extraversion than controls. They also had significantly lower contingent negative variation (CNV), higher postimperative negative variation and lower whole blood serotonin values than controls. Within the patient group, vulnerability to parasuicide, as determined by previous or repeated acts of deliberate self-harm, was associated with higher scores for hopelessness and suicide intent, lower scores for extraversion and decreased CNV. Factor analysis revealed significant correlations between psychological variables and auditory evoked potential amplitudes for the vulnerable group. A profile of variables associated with increased risk of self-harm in patients presenting with attempted suicide is proposed from our data. PMID- 7872035 TI - Predicting suicide attempts among adolescents. AB - This study set out to investigate the utility of 4 often referred to behavioural antecedents of suicide attempts--suicide ideation, plans, threats and deliberate self-harm--in the prediction of suicide attempts and the identification of suicide attempters and nonattempters among adolescents. A total of 156 male and 151 female students aged between 14 and 17 years (mean = 15.8) attending one randomly chosen metropolitan state high school completed a questionnaire concerning a number of aspects of suicidal behaviour. The findings indicated that suicide ideation, plans and threats, and deliberate self-harm are associated with suicide attempting and that a combination of suicide plans and deliberate self harm present a particularly worrying mixture. Further, a composite index of suicidality was demonstrated to have some utility in the identification of suicide attempters and nonattempters. These findings add further weight of evidence to the suggestion that adolescents who enter the spectrum of suicide behaviours are at high risk of making a suicide attempt, although this requires further investigation in a prospective study. PMID- 7872037 TI - Diagnosis of schizophrenia in a matched sample of Australian aborigines. AB - Cross-cultural phenomenology is one method of studying mental disorders such as schizophrenia. There are few data of this nature available on Australian aborigines. Using a retrospective medical record review of 39 matched pairs of aboriginal and nonaboriginal patients discharged as schizophrenic from a psychiatric hospital, this study investigated whether any phenomenological differences, using DSM-III-R criteria, existed between the two groups. Of all criteria, bizarre delusions, social deterioration, illness duration and organic exclusion were statistically significant, with fewer aboriginal subjects having documentation for each of these variables. Possible explanations for these findings, including intergroup phenomenological differences and assessment variation, are discussed. PMID- 7872036 TI - Ten-year course of schizophrenia--the Madras longitudinal study. AB - Ninety first-episode patients fulfilling ICD-9 criteria for schizophrenia were followed up prospectively for 10 years. Complete assessments were possible on 76. The pattern of illness was good in 67% of the cases, and the commonest patterns was one with recurrent episodes. Predictors of poor course and longer time spent in psychosis were identified. All positive and negative symptoms showed a steep decline at the end of 10 years. The results are discussed in the context of longitudinal research on the course of schizophrenia in developing countries. PMID- 7872039 TI - Suicide in South Africa. An analysis of nationally registered mortality data for 1984-1986. AB - Nationally registered suicide mortality data for South Africa (1984-1986) were analysed. There were 5448 deaths (1.3%) due to suicide in this period. Proportional mortality and mean annual suicide mortality rates were highest for whites, followed by Asians and then coloureds. The proportional mortality for blacks was similar to that of coloureds. Suicide was relatively prominent as a cause of death for Asian females (15-24 years). For whites, the most commonly used method of suicide was firearms. Except for coloured females, hanging was the most common method used for the other population groups. Political, economic, and religious factors may account for some of the differences. Cultural factors may explain the findings for young Asian females. There is a need for strict gun control legislation. PMID- 7872038 TI - Axis V--Global Assessment of Functioning Scale. Evaluation of a self-report version. AB - The present study examines a self-report version of the Global Assessment of Functioning Scale according to Axis V (GAF self-report). The sample (n = 73) was a psychiatric outpatient population from a catchment area clinic. Patients with psychotic and organic mental disorders were not included. The diagnostic distribution on Axis I was similar to the findings from previous studies. Axis II disorders were identified among 47%, of whom a majority also had a concomitant Axis I disorder. The mean GAF expert score was 66.5 (range: 48-86). High complexity and severity of disorders and a high number of fulfilled Axis II criteria were significantly associated with low GAF scores. Independent expert ratings on GAF were correlated with the GAF self-report overall at r = 0.62, varying from 0.45 to 0.91 between different diagnostic groups. In general, the patients scored themselves lower (mean: -4.4 units) than expert ratings. Patients with depressive symptoms from an adjustment disorder or mood disorder were most prone to underestimation. Women also tended to score themselves lower than experts did. Conclusively, the GAF self-report turned out to be a valid and reliable unidimensional instrument measuring psychological, social and occupational functioning. The GAF is easy to handle, and with a self-report version as a complement, Axis V could be more frequently used in future clinical practice and research. PMID- 7872040 TI - Neuroleptic dose and schizophrenic symptoms. A survey of prescribing practices. AB - A study was conducted to survey the prescribing practices of neuroleptic doses in 100 consecutively hospitalized DSM-III-R schizophrenic patients. The relationship between doses and clinical and symptomatological variables was subsequently analyzed. Patients were evaluated through the Positive and Negative Syndrome Scale (PANSS). The peak mean dose in chlorpromazine equivalents was 1290 (range 250-7200). Haloperidol was the most commonly employed neuroleptic (67 patients). Neuroleptic doses were correlated with excitement, suspiciousness, hostility, uncooperativeness and poor impulse control. The neuroleptic doses administered in our hospital were similar to those found in other survey reports but higher than those recommended by the controlled dose-response studies. The correlation found between neuroleptic doses and symptoms of disruptive behavior suggests that we employed high-dose practices to treat the disruptive symptoms of schizophrenia. We concluded that it is useful to distinguish between the neuroleptic doses required to control the psychotic episode and those to treat the disruptive behavior. PMID- 7872041 TI - The Australian multicentre double-blind comparative study of remoxipride and thioridazine in schizophrenia. AB - A double-blind, randomized study of parallel group design comparing remoxipride and thioridazine (dose range 150-600 mg/day of either drug) was undertaken at 11 Australian centres. A total of 144 patients (remoxipride = 73, thioridazine = 71) with DSM-III-R schizophrenia or schizophreniform disorder commenced the study, and 89 patients (remoxipride = 45, thioridazine = 44) completed the 6 weeks of the trial. The mean daily doses at last rating were 404 mg (remoxipride) and 378 mg (thioridazine). Initial Brief Psychiatric Rating Scale scores decreased by a mean 8.7 points in both remoxipride and thioridazine groups. Equivalent treatment responses were also confirmed by Clinical Global Impression. During the study, sedatives or hypnotics were needed by 68% of the remoxipride patients and 51% of the thioridazine patients. Thioridazine was associated with more postural hypotension, drowsiness, increased sleep, headache, dizziness on rising, dry mouth, sexual dysfunction and weight gain, while remoxipride patients reported more insomnia. There were no differences between remoxipride and thioridazine on dystonia, hypokinesia, dyskinesia, rigidity and akathisia. The results indicate that remoxipride has similar antipsychotic efficacy to thioridazine but causes fewer side effects. PMID- 7872043 TI - The reliability of DSM-III prodromal symptoms in first-episode psychotic patients. AB - Thirty-one first-episode psychotic patients were assessed via a semistructured interview to determine the presence or absence of the 8 DSM-III prodromal symptoms. Interrater reliability data were calculated for the same symptoms according to the patient, an informant and the raters blending the previous 2 sources of information. Levels of reliability, reported as kappa and percentage agreements, were generally acceptable. PMID- 7872042 TI - A family study of anxiety disorders: familial transmission and relationship to mood disorder and psychoactive substance use disorder. AB - The prevalence of mental disorders in 76 first-degree relatives (parents and nontwin siblings) of 33 subjects with anxiety disorder was compared with the prevalence of mental disorders in 45 first-degree relatives of 20 subjects with mood disorder and 13 first-degree relatives of 6 subjects with psychoactive substance use disorder. All subjects were personally interviewed with the Structured Clinical Interview for DSM-III-R Axis I (SCID I). Interrater reliability was high for most diagnoses. Significantly more first-degree relatives of subjects with anxiety disorder had panic disorder and generalized anxiety disorder compared with relatives of probands with mood disorder. Significantly more female than male relatives of anxiety subjects suffered from anxiety disorders; there were no gender differences in the prevalence of anxiety disorders in relatives of mood and psychoactive substance use disorder (PSUD) subjects. The combination of anxiety and mood disorder was overrepresented in first-degree relatives of subjects with the same type of comorbidity. In relatives of subjects with mixed anxiety and psychoactive substance use disorder, but no mood disorder, there was an overrepresentation of PSUD; mainly alcohol abuse or dependence. PMID- 7872044 TI - Patient satisfaction with inpatient psychiatric care. The influence of personality traits, diagnosis and perceived coercion. AB - The aim of the study was to investigate the influence of personality traits, diagnosis and perceived coercion on patient satisfaction with inpatient psychiatric care. The study was performed as a cross-sectional study on 7 inpatient wards in southern Sweden. A cohort of 50 psychiatric inpatients evaluated satisfaction with care and also made ratings on a personality questionnaire. Patients with a higher level of the trait aggressive nonconformity were significantly less satisfied with the ward's physical and psychosocial environment, the treatment design and the treatment program. The phenomenon of acquiescence was not related to the reported level of satisfaction. Analyses of patient satisfaction according to diagnostic groups showed that patients with affective disorders had significantly better satisfaction than patients with a diagnosis of schizophrenia. Patients who perceived that they were involuntarily admitted were measured as being significantly less satisfied with the care in all areas. It is concluded that, to attain a higher specificity in analyses of variation in patient satisfaction, focus may be put on situational and setting factors of the care delivered along with specific patient characteristics. Risk groups, which require great attention in the development of quality assessment and quality assurance policies, are patients with schizophrenia and patients who perceive coercion in connection with inpatient psychiatric treatment. PMID- 7872046 TI - Synchronized annual rhythms in violent suicide rate, ambient temperature and the light-dark span. AB - To investigate whether violent and nonviolent suicide and homicide are related to atmospheric or geomagnetic activity, we investigated the relationships between weekly number of suicides or homicides for all Belgium for the period 1979-1987, and ambient temperature, relative humidity, air pressure, hours of sunlight and precipitation per day, wind speed and geomagnetic index. The occurrence of violent suicide was significantly and positively related to ambient temperature, sunlight duration, an increase in temperature over the few past weeks, and negatively to relative humidity. Higher ambient temperature and an increase in air temperature over the few past weeks were the most significant climatic predictors of violent suicide rate. A highly significant common annual rhythm with a common acrophase of 190 degrees was detected in violent suicide rate, ambient temperature and sunlight duration. No significant time-relationships between nonviolent suicide or homicide and any of the weather variables were found. It is concluded that i) violent suicide may be related to short-term fluctuations in the weather and in particular to temperature; and ii) the annual rhythm in violent suicide may be synchronized by the annual rhythms in ambient temperature and light-dark span. PMID- 7872045 TI - Neurological abnormalities in patients with schizophrenia or schizophreniform disorder at first admission to hospital: correlations with computerized tomography and regional cerebral blood flow findings. AB - Forty-five patients with schizophrenia or schizophreniform disorder admitted to hospital for the first time had a neurological examination, including integrative sensory and complex motor acts, by a trained neurologist. The patients were studied by CT (computerized tomography) and rCBF (regional cerebral blood flow) as well. A control group of 24 healthy volunteers was included. The patients had significantly more neurological abnormalities (NA) than the healthy volunteers. Medication did not explain the discrepancy. The NA were associated with sulcal enlargement and smaller brains as visualized by CT but not with ventricular enlargement. There was no association between the regional flow values and NA. PMID- 7872047 TI - High levels of free testosterone in women with bulimia nervosa. AB - Women with normal-weight bulimia nervosa (n = 11) displayed significantly higher serum levels of free testosterone than age-matched controls (6.0 +/- 0.7 vs 3.9 +/- 0.8 pmol/l; P = 0.03). The possible importance of androgens, in women, for the pathophysiology of conditions characterized by an impairment in impulse control is being discussed. PMID- 7872048 TI - Human osteoblastic cells: a potential tool to assess the etiology of pathologic bone formation. PMID- 7872049 TI - Bone mineral density at distal tibia using dual-energy X-ray absorptiometry in normal women and in patients with vertebral osteoporosis or primary hyperparathyroidism. AB - To assess the effect of age and disease on mineral distribution at the distal third of the tibia, bone mineral content (BMC) and bone mineral density (BMD) were measured at lumbar spine (spine), femoral neck (neck), and diaphysis (Dia) and distal epiphysis (Epi) of the tibia in 89 healthy control women of different age groups (20-29, n = 12; 30-39, n = 11; 40-44, n = 12; 45-49, n = 12; 50-54, n = 12; 55-59, n = 10; 60-69, n = 11; 70-79, n = 9), in 25 women with untreated vertebral osteoporosis (VOP), and in 19 women with primary hyperparathyroidism (PHPT) using dual-energy x-ray absorptiometry (DXA; Hologic QDR 1000 and standard spine software). A soft tissue simulator was used to compensate for heterogeneity of soft tissue thickness around the leg. Tibia was scanned over a length of 130 mm from the ankle joint, fibula being excluded from analysis. For BMC and BMD, 10 sections 13 mm each were analyzed separately and then pooled to define the epiphysis (Epi 13-52 mm) and diaphysis area (Dia 91-130 mm). Precision after repositioning was 1.9 and 2.1% for Epi and Dia, respectively. In the control group, at any site there was no significant difference between age groups 20-29 and 30-39, which thus were pooled to define the peak bone mass (PBM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872050 TI - Parathyroidectomy does not prevent bone loss in the oophorectomized rat. AB - The evidence for a role of parathyroid hormone in the bone loss after the menopause remains controversial. This study examines the effect of parathyroidectomy on femoral trabecular bone volume, thickness, and spacing and biochemical markers of bone turnover in the oophorectomized rat. Female Sprague Dawley rats 3 months old were double sham operated (sham), oophorectomized (OPX), parathyroidectomized (PTX), or oophorectomized and parathyroidectomized (O/P) under halothane anesthesia. At 9 weeks postoperation, femoral trabecular bone volume (BV/TV) was lower in OPX and O/P rats compared with sham or PTX animals (BV/TV, %, mean +/- SEM): sham 25.9 +/- 0.5, OPX 15.1 +/- 0.9, PTX 24.1 +/- 0.9, O/P 17.3 +/- 0.5; p < 0.001). Urinary hydroxyproline excretion, serum osteocalcin, and alkaline phosphatase activity were higher in OPX and O/P rats compared with control animals at 3 weeks postoperation (OHPE microM GF, mean +/- SEM: sham 1.37 +/- 0.16, OPX 2.16 +/- 0.26, PTX 0.95 +/- 0.21, O/P 1.92 +/- 0.22, p < 0.005; osteocalcin, microgram/liter, sham 31.8 +/- 1.8, OPX 33.7 +/- 2.7, PTX 24.5 +/- 2.1, O/P 34.3 +/- 2.1, p < 0.025; alkaline phosphatase, U/liter, sham 90 +/- 3, OPX 125 +/- 9, PTX 87 +/- 9, O/P 116 +/- 11, p < 0.005). These data indicate postoophorectomy bone loss is not prevented by parathyroidectomy. PMID- 7872051 TI - Osteoporosis in African hemosiderosis: role of alcohol and iron. AB - This paper aims to examine the relative contributions made by alcohol and iron overload and hypovitaminosis C to the osteoporosis associated with African hemosiderosis. To characterize this bone disorder, we examined double tetracycline-labeled iliac crest bone biopsies and serum biochemistry in 53 black male drinkers, 38 with (Fe+) and 15 without (Fe-) iron overload, and in controls. We reasoned that abnormalities found in both patient groups were likely to be caused by alcohol abuse and those found only in the Fe+ group to be caused by iron overload and hypovitaminosis C (iron/C-). The patient groups differed only with respect to greater erosion depth (p < 0.05) and abnormal markers of iron overload in the Fe+ group. Ascorbic acid levels were lower in the Fe+ group than in controls (p < 0.001). Bone volume and trabecular thickness were significantly lower in both patient groups compared with controls and therefore likely caused by alcohol. There were no positive correlations between formation and erosion variables in either patient group, which suggests uncoupling of formation from erosion, possibly as a result of alcohol abuse. Prolonged mineralization lag time associated with thin osteoid seams was found in 32% of patients, affecting both groups. This rules out osteomalacia and suggests osteoblast dysfunction, probably caused by alcohol. The number of iron granules in the marrow correlated with erosion depth (r = 0.373, p < 0.01), trabecular number (r = -0.295, p < 0.05), and trabecular separation (r = 0.347, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872052 TI - Structural requirements for bisphosphonate actions in vitro. AB - We investigated the structural requirements for the binding of bisphosphonates to bone mineral and the relation between their affinity for bone and their effects on bone resorption in vitro. For this we used fetal mouse long bones in culture and bisphosphonates with variable R1 and R2 structures. In addition, we studied the effect of structural differences in the incorporation of calcium into bone. We found that bisphosphonates containing a hydroxyl group in the R1 position have the highest affinity for bone mineral. This was related to their capacity to inhibit the incorporation of calcium into long bones but not to their antiresorptive potency. The latter was primarily determined by R2. Furthermore, the effect of bisphosphonates on calcification, but not on resorption of bone explants, was mainly determined by the mode of addition. The continuous presence of bisphosphonate during culture inhibited calcification even at very low concentrations, but short incubation of the bones with relatively high concentrations had no effect. This is probably a result of differences in the availability of the compound to the process of calcification. Because, in vivo, the more potent bisphosphonates inhibit resorption without adversely affecting mineralization of the skeleton and they disappear rapidly from the circulation after administration, we suggest that cultures of bone explants incubated with bisphosphonates for short times rather than cultures in which the drugs are continuously present provide more accurate information about the in vivo effect of these compounds on both resorption and calcification. PMID- 7872053 TI - Posture, age, menopause, and osteopenia do not influence the circadian variation in the urinary excretion of pyridinium crosslinks. AB - This study was performed to investigate whether the circadian variation in urinary pyridinium crosslinks is related to physical activity, age, the menopause, and asymptomatic osteopenia. We measured urinary pyridinoline/creatinine (Pyr/Cr) and deoxypyridinoline/creatinine (D-Pyr/Cr) in 9 healthy premenopausal women in two 27 h studies, before and at the end of 5 days of total bed rest. Both Pyr/Cr and D-Pyr/Cr showed highly significant circadian variations, with the peak at night and the nadir during the day (p < 0.001). The 5 days of complete bed rest produced no changes in the circadian pattern, but a general increase of 28% was observed in pyridinium crosslinks. A group of 12 healthy, early postmenopausal women (aged 55 +/- 2 years), 12 healthy, elderly postmenopausal women (aged 73 +/- 1 years), and 12 elderly osteopenic but otherwise healthy women (aged 73 +/- 1 years) were also studied for 27 h. All three groups showed highly significant (p < or = 0.001) circadian variations in the urinary excretion of pyridinium crosslinks. As expected, both Pyr/Cr (p < 0.05) and D-Pyr/Cr (p < 0.001) increased at the time of menopause, but the circadian variations in Pyr/Cr and D-Pyr/Cr were similar in all groups studied. We conclude that the circadian variation in the urinary excretion of pyridinium crosslinks is independent of physical factors. Furthermore, the circadian variation in pyridinium crosslinks was not related to age, menopausal status, or asymptomatic osteopenia. PMID- 7872054 TI - Trochanteric bone mineral density is associated with type of hip fracture in the elderly. AB - Hip fractures can be separated into femoral neck (cervical or intracapsular) or trochanteric (extracapsular). Trochanteric fractures have been associated with up to twice the short-term mortality of cervical fractures in the elderly. Fracture type may be influenced by the fall direction and local differences in proximal femur strength properties. We previously demonstrated that fall characteristics and body habitus, in addition to femoral bone mineral density, play a dominant role in the prediction of hip fracture in elderly fallers. To examine the association of these determinants with hip fracture type, we assessed fall characteristics, body habitus, and site-specific bone mineral density measurements in 112 elderly hip fracture patients (85 women and 27 men, mean age 85 years) 1 week after an acute hip fracture. Trochanteric BMD was 13% lower in women and 11% lower in men for patients with trochanteric fracture than in those with femoral neck fracture (p < 0.01). A stepwise multiple logistic regression indicated that trochanteric BMD (decrease of 1.0 SD, adjusted OR 4.6, 95% Cl 2.0 9.5, p < 0.0001) and femoral neck BMD (increase of 1.0 SD, adjusted OR 3.0, 95% Cl 1.6-5.9, p = 0.0003) were independently associated with trochanteric fracture. Fall characteristics, body habitus, gender, and age were not associated with hip fracture type. We conclude that a relatively low trochanteric BMD or a high femoral neck BMD was associated with a trochanteric hip fracture and that site specific trochanteric BMD determinations should be measured when assessing risk of trochanteric hip fractures in the elderly. PMID- 7872055 TI - Variation in vertebral height ratios in population studies. European Vertebral Osteoporosis Study Group. AB - Vertebral height ratios are used to define vertebral deformity in clinical and epidemiologic studies of vertebral osteoporosis. However, few data have been obtained on the variation in these ratios in different populations using standard methods. We examined vertebral morphometric measurements obtained in a population survey from three centers: Malmo (Sweden), Montceau-les-Mines (France), and Graz (Austria), to study the influence of sex and the population center on vertebral height ratios. Radiographs were obtained according to a standardized protocol, and morphometric measurements, anterior height Ha, central height Hc, and posterior height Hp, made in Berlin. The height ratios anterior, Ha/Hp, central, Hc/Hp, posterior I, Hp/Hp', and posterior II, Hp/Hp" (Hp' = posterior height of vertebrae above, Hp" = posterior height of vertebrae below) were calculated for each vertebra from T4 to L4. The mean and standard deviation of these ratios for each sex and each center were derived using a statistical trimming procedure to normalize the distribution. Threshold values for defining grade 1 and grade 2 deformities, wedge, biconcavity, and compression, were calculated using these parameters. Anterior and central vertebral height ratios were smaller in males than females (p < 0.01). There were significant differences between the three centers (p < 0.01) both in the trimmed mean values for anterior and central vertebral height ratios and in the thresholds derived using standard criteria for defining wedge and biconcavity deformity. The data confirm the impression from single-center studies that vertebral height ratios vary between populations and suggest that reference values for vertebral height ratios should be derived separately for males and females within individual populations whenever possible. PMID- 7872056 TI - Fractal organization of trabecular bone images on calcaneus radiographs. AB - Bone density is not the unique factor conditioning bone strength. Trabecular bone microarchitecture also plays an important role. We have developed a fractal evaluation of trabecular bone microarchitecture on calcaneus radiographs. Fractal models may provide a single numeric evaluation (the fractal dimension) of such complex structures. Our evaluation results from an analysis of images with a varying range of gray levels, without binarization of the image. It is based on the fractional brownian motion model, or more precisely on the analysis of its increment, the fractional gaussian noise (FGN). The use of this model may be considered validated if two conditions are fulfilled: the gaussian repartition and the self-similarity of our data. The gaussian repartition of intermediate lines of these images was tested on a sample of 32,800 lines from 82 images. Following a chi-square goodness-of-fit test, it was checked in 86% of these lines for alpha = 0.01. The self-similarity was tested on 20 images by two estimators, the variance method of Pentland and the spectrum method of Fourier. Self similarity is defined by lined-up points in a log-log plot of the FGN spectrum or of the variance as a function of the lag. We found two self-similarity areas between scales of analysis ranging from 105 to 420 microns, then above 900 microns, where linear regression produced high mean correlation coefficients (r > or = 0.97). Following this validation, we studied the reproducibility of this new technique. Intra- and interobserver reproducibility, influence of transferring the region of interest, and long-term reproducibility were assessed and given CV of 0.61 +/- 0.15, 0.68 +/- 0.47, 0.53 +/- 0.16, and 2.07 +/- 0.84%, respectively. These data have allowed us to validate the use of this fractal model by checking the fractal organization of our radiographic images analyzed by the model. The good reproducibility of successive x-rays in the same subject allows us to undertake population studies and to envisage longitudinal series. PMID- 7872057 TI - Effect of administration and subsequent cessation of buserelin on cancellous bone of female rats. AB - Although hormone replacement therapy is effective in preventing postmenopausal bone loss, it fails to cause a return of bone mass to normal in patients with established osteoporosis. Similarly, in the ovariectomized rat, estrogen administration protects the skeleton from bone loss but fails to reverse this once it has occurred. However, physiologically produced sex steroids may, in contrast to conventional methods of sex steroid administration, be capable of restoring bone mass in osteopenic states. To investigate this question, we analyzed the effect of treatment with the LHRH agonist buserelin for varying durations, and subsequent cessation thereof, on histomorphometric indices of rat cancellous bone. Female rats 13 weeks old were given daily SC injections of vehicle or buserelin as follows: vehicle days 1-90; vehicle days 1-150; vehicle days 1-60, buserelin days 61-90; vehicle days 1-60, buserelin days 61-90, vehicle days 91-150; vehicle days 1-30, buserelin days 31-90; vehicle days 1-30, buserelin days 31-90, vehicle days 91-150; buserelin days 1-90; buserelin days 1 90, vehicle days 91-150. At the end of the treatment period, animals were killed, tibiae removed, and histomorphometric indices assessed at the secondary spongiosa of the proximal metaphysis. Analysis of vaginal smears confirmed that buserelin rapidly suppressed ovulation, which quickly returned once treatment was stopped. We found that administration of buserelin for 30, 60, or 90 days reduced cancellous bone volume because of a reduction in both the number and thickness of trabeculae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872058 TI - Cholera toxin-stimulated bone resorption in cultured mouse calvarial bones not inhibited by calcitonin: a possible interaction at the stimulatory G protein. AB - We examined the effect of calcitonin in cultured mouse calvarial bones after prestimulation with different activators of adenylyl cyclase. Calcitonin (100 ng/ml), added after 48 h of culture, inhibited bone resorption (assessed as release of 45Ca from prelabeled bones cultured for 96-144 h) stimulated with parathyroid hormone (PTH, 10 nM; 0-144 h) or the adenylyl cyclase stimulator forskolin (2 microM; 0-144 h). However, no effect of calcitonin was demonstrated when bone resorption was prestimulated with the adenylyl cyclase stimulator cholera toxin, at and above 1 ng/ml, at any time point studied. In contrast, two other types of inhibitors of bone resorption in vitro, the carbonic anhydrase inhibitor acetazolamide (10 microM) and the aminobisphosphonate AHPrBP (10 microM), significantly inhibited cholera toxin-stimulated bone resorption. No cyclic AMP response to calcitonin was seen after preculture for 48 h with cholera toxin (0.1-100 ng/ml), although bones precultured in basic medium, in the absence or presence of forskolin, were still able to respond to calcitonin with elevation of cyclic AMP. Binding studies with [125I]calcitonin demonstrated that the preculture with cholera toxin did not affect the binding of calcitonin to the receptor. In summary, our data show that cholera toxin pretreatment makes calvarial bones insensitive to calcitonin-induced inhibition of bone resorption as a result of an interaction with cholera toxin at the level of calcitonin receptor-linked signal transduction. We suggest that the interaction, distal to the calcitonin receptor, is caused by the irreversible activation of Gs produced by cholera toxin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872059 TI - Inhibition of collagen synthesis by prostaglandins in the immortalized rat osteoblastic cell line Py1a: structure-activity relations and signal transduction mechanisms. AB - We previously showed that prostaglandin E2 (PGE2) can selectively inhibit collagen synthesis and gene transcription in the immortalized rat osteoblastic clonal cell line Py1a, particularly in the presence of insulin-like growth factor I (IGF-I). In the present study, we examined the structure-activity relations for this effect. PGF2 alpha was approximately 100 times more potent than PGE2. The prostaglandin F receptor (FP) selective agonist, fluprostenol, was the most potent agonist tested, significantly inhibiting incorporation of [3H]proline into both collagen and noncollagen protein at 10(-11) M, with more than 90% inhibition of collagen synthesis at 10(-8) M. The PGE2 analog, sulprostone, and PGD2 showed activity similar to that of PGE2. PGI2 and its stable analog, carbacyclin, were the least effective. Parathyroid hormone (PTH), forskolin, and isobutylmethylxanthine (IBMX) were ineffective. Phorbol myristate acetate (PMA) inhibited collagen synthesis in a manner similar to that of the prostanoids. The inhibitory effects of PGF2 alpha, fluprostenol, and PMA show a similar time course on alpha 1(I) procollagen mRNA levels. The inhibition appeared to be caused by a decrease in collagen gene transcription as measured by nuclear run-on analysis. Further evidence for a transcriptional effect was obtained with COL1A1 promoter-CAT reporter constructs, although these showed somewhat smaller effects of prostanoids on CAT activity than on mRNA levels or labeling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872060 TI - Comparison of four methods for cross-calibrating dual-energy X-ray absorptiometers to eliminate systematic errors when upgrading equipment. AB - Dual-energy x-ray absorptiometry (DXA) is a widely employed technique for making noninvasive measurements of bone mineral density (BMD). Advances in DXA technology have resulted in the development of new densitometers that offer increased scan speed, improved spatial resolution, and the ability to make measurements at additional skeletal sites. However, changing from a first to a second-generation DXA system generates two additional potential sources of error. First, if the densitometers produce results that are substantially different, diagnostic errors occur if the results from both instruments are compared to the same normative database. Second, even if the densitometers produce results that are nearly identical, small systematic errors may influence interpretation of serial bone density measurements in individual patients. To assess the impact of changing from a first- to a second-generation DXA scanner, we made measurements using the standard "pencil beam" mode on 133 consecutive patients using both a Hologic QDR-1000 and a QDR-2000 densitometer when the latter instrument was calibrated according to the manufacturer's routine procedure using a single anthropomorphic spine phantom. We then recalculated the results for the QDR-2000 densitometer using cross-calibration factors based on (1) a regression line generated by scanning three anthropomorphic spine phantoms whose BMD ranged from osteoporotic to high normal on each instrument, (2) an adult human lumbar spine embedded in tissue-equivalent plastic, or (3) a regression line derived from scans of the first 83 patients that was then applied to the last 50 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872061 TI - Pharmacokinetics of clodronate in renal failure. AB - The pharmacokinetic parameters describing the fate of one intravenous clodronate (disodium dichloromethane diphosphonate) dose was studied in 24 normal subjects and in 24 patients with different degrees of renal insufficiency. The aim of the study was to derive data for adjustment of dosage in relation to renal function. Disodium clodronate in serum and urine samples was analyzed by capillary gas chromatography with mass-selective detection. The renal clearance (CLR) of clodronate was highly dependent on renal function and declined successively with declining glomerular filtration rate (GFR). Plasma clearance (CLP) declined, too, but to a lesser degree than CLR. The impairment of renal function resulted in decreased cumulative urinary elimination of clodronate and increased total areas under the serum concentration-time curve (AUC0-infinity). Hence, as the renal elimination of clodronate diminishes with decreasing GFR, there is a related retention of the substance. As a result of the present study, the following dosages are recommended: creatinine clearance (CLCr) from 50 to 80 ml/minute, 75 100% of normal dose; CLCr 12-50 ml/minute, 50-75% of normal dose; and ClCr < 12 ml/minute, 50% of normal dose. The results must be interpreted with caution in patients with malignancy and severe skeletal disease, in whom the nonrenal clearance may vary markedly. PMID- 7872062 TI - Femoral bone loss progresses with age: a longitudinal study in women over age 65. AB - Although previous longitudinal studies suggest bone loss ceases at the spine and radius in women over age 65, few data are available to determine whether femoral bone loss continues in this age group. Because a low femoral bone mass is associated with an increased risk of hip fracture and current therapies for fracture prevention focus on halting bone loss, it is imperative to determine whether femoral bone loss occurs in those who sustain 90% of hip fractures: women over age 65. To determine the annual rate of femoral bone loss, the association of bone loss and age, and the relationship between femoral and spinal bone loss in this age group, we prospectively followed femoral and spinal bone mineral density (BMD) in 85 healthy, community-dwelling, ambulatory women over age 65 (mean 77 years, range 66-93 years). Measurements of femoral and spinal BMD were assessed twice over 1 year using dual-energy x-ray absorptiometry. Cross sectional analysis of site-specific baseline BMD suggested a significant bone loss in the femoral neck (-0.76% per year, p < 0.01), total hip (-0.70% per year, p < 0.01), trochanter (-0.71% per year, p < 0.05), intertrochanter (-0.88% per year, p < 0.01), and Ward's triangle (-0.86% per year, p < 0.01) but no significant change at the spine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872063 TI - Bone-forming ability of 24R,25-dihydroxyvitamin D3 in the hypophosphatemic mouse. AB - To determine whether 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] exerts unique biologic effects on bone, we examined the effects of the vitamin D metabolites, 24R,25(OH)2D3 and 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], on the hypophosphatemic (Hyp) mouse, a model for X-linked hypophosphatemic rickets in humans. The Hyp mice were administered 1-10,000 micrograms/kg/day of 24R,25(OH)2D3, 0.01-10 micrograms/kg/day of 1 alpha,25(OH)2D3, or vehicle alone, given daily for 28 days by intraperitoneal injection. 24R,25(OH)2D3 at doses of 1 1000 micrograms/kg/day had dose-dependent effects in increasing bone size, dry bone weight, and bone mineral content without causing hypercalcemia. 1 alpha,25(OH)2D3 at doses of 1 or 10 micrograms/kg/day, which we considered to have activity similar to that of 1000 micrograms/kg/day of 24R,25(OH)2D3 with respect to cell differentiation activity, caused severe bone resorption and hypercalcemia. At 0.1 microgram/kg/day, 1 alpha,25(OH)2D3 increased bone size, similarly to a dose of 1000 micrograms/kg/day of 24R,25(OH)2D3, without significantly affecting dry bone weight or bone mineral content, as did 1000 micrograms/kg/day of 24R,25(OH)2D3. These findings suggest that 24R,25(OH)2D3 exerts unique activity in the Hyp mouse rather than merely mimicking the activity of 1 alpha,25(OH)2D3. PMID- 7872064 TI - Premenopausal and postmenopausal changes in bone mineral density of the proximal femur measured by dual-energy X-ray absorptiometry. AB - Total and regional bone mineral density (BMD) of the proximal femur was measured by DXA in 1238 healthy white women. In the 389 premenopausal women, aged 21-54 years, no bone loss was observed before the menopause, except in the femoral neck and Ward's triangle, in which BMD decreased by 0.3%/year (SEE 0.2-0.9%/year, p < 0.001) and 0.6%/year (SEE 0.4-0.8%/year, p < 0.001), respectively. In the postmenopausal women aged 48-75 years, there was a highly significant exponential decay in BMD with age and years since menopause (YSM) in all regions (-0.58 < r < -0.48, p < 0.001). However, YSM was a better predictor of BMD than age. The decrease in BMD in the first 5 years postmenopause reached values of 9-13%. The estimated bone loss after 20 years was 17-30%, greatest in Ward's triangle and smallest in the intertrochanteric region. BMD correlated highly significantly with BMI (0.26 < r < 0.48, p < 0.001). In conclusion, the present study indicates a stable premenopausal bone mass of the proximal femur and a postmenopausal bone loss, which is influenced mainly by YSM within the first 10-15 years after menopause. BMD correlated with body mass index (BMI) in the postmenopausal years, confirming that low BMI constitutes a potential risk factor for osteoporosis. PMID- 7872065 TI - Activation of the human osteocalcin gene by 24R,25-dihydroxyvitamin D3 occurs through the vitamin D receptor and the vitamin D-responsive element. AB - 1 alpha-25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], together with vitamin D receptor (VDR), directly activates human osteocalcin (hOC) gene expression through a vitamin D-responsive element (VDRE) located in the promoter of the hOC gene. We investigated the effect of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] on the regulation of the hOC gene promoter and compared it with that of 1 alpha,25(OH)2D3. 24R,25(OH)2D3 did not activate the natural promoter in VDR negative CV-1 cells. 24R,25(OH)2D3, however, induced the activation of this promoter following cotransfection with an hVDR expression vector. In VDR-positive MC3T3-E1 cells, 24R,25(OH)2D3 activated not only the natural hOC promoter but also a chimeric promoter composed of a synthetic hOC VDRE sequence linked to the thymidine kinase promoter. In combination with 1 alpha-25(OH)2D3, 24R,25(OH)2D3 did not exhibit any antagonist activity on the hOC promoter. These results suggest that under conditions of high 24R,25(OH)2D3 levels in vivo, this metabolite of vitamin D3 may activate hOC gene expression through receptor mechanisms identical to that for 1 alpha,25(OH)2D3. PMID- 7872066 TI - Direct demonstration that the vitamin K-dependent bone Gla protein is incompletely gamma-carboxylated in humans. AB - Incomplete vitamin K-dependent gamma-carboxylation has been found in bone Gla protein (BGP) isolated from each of 20 different human bone samples. Using N terminal protein sequencing of the methyl-esterified protein (Anal Biochem 1991;199:93-97), a method that directly measures the percentage of gamma carboxylation at each target glutamate residue, the extent of incomplete BGP gamma-carboxylation was found to depend strongly on sequence position, with (chi +/- SD) 67 +/- 14% gamma-carboxylation at residue 17.88 +/- 9% gamma carboxylation at residue 21, and 93 +/- 4% gamma-carboxylation at residue 24. There is a strong correlation between the incomplete gamma-carboxylation at glutamate residues 17 and 21 for BGP purified from the 20 bone samples (p < 0.001), which suggests that individual differences in the efficiency of BGP gamma carboxylation during synthesis probably cause the observed differences in percentage BGP gamma-carboxylation between bone samples. These results have been interpreted using a kinetic treatment of gamma-carboxylation. This treatment predicts the existence of differences in the extent of gamma-carboxylation between glutamate residues in BGP, as well as the correlation between percentage carboxylation at Glu17 and Glu21. Although the molecular basis of incomplete BGP gamma-carboxylation is at present unknown, if incomplete BGP gamma-carboxylation were caused only by differences in the availability of vitamin K in bone cells, this kinetic treatment predicts that the range in BGP gamma-carboxylation observed in the 20 human bone samples studied here could be explained by a relatively modest fivefold range in the vitamin K levels of these individuals. PMID- 7872068 TI - Eric Neil (1918-1990): an appreciation. PMID- 7872067 TI - Bone morphogenetic protein 2 increases insulin-like growth factor I and II transcripts and polypeptide levels in bone cell cultures. AB - Insulin-like growth factors (IGF) I and II are among the most prevalent growth factors secreted by bone cells and are presumed to act as autocrine regulators of bone formation. Certain growth factors, synthesized by skeletal cells and known to stimulate the replication but not the differentiated function of cells of the osteoblastic lineage, have been shown to inhibit skeletal IGF-I and II synthesis. We postulated that growth factors with limited mitogenic activity and with differentiation-inducing properties, such as bone morphogenetic protein (BMP) 2, have the opposite effect and enhance IGF-I and II synthesis. We tested the effects of BMP-2 on IGF-I and II mRNA expression and polypeptide concentrations in cultures of osteoblast-enriched (OB) cells from 22 day fetal rat calvariae. Steady-state IGF-I and II mRNA levels were determined by northern blot analysis, and IGF-I and II concentrations were determined in acidified and fractionated culture medium by a specific radioimmunoassay. After 24-48 h of treatment, BMP-2 at 3.3 nM increased IGF-I and II transcripts by up to twofold and polypeptide levels by up to fourfold. BMP-2 was a more potent stimulator of IGF-II synthesis, and it was active at doses as low as 0.03 nM for IGF-II mRNA and 0.3 nM for IGF II protein, whereas a dose of 3.3 nM was required to observe the effect on IGF-I synthesis. The effects of BMP-2 on IGF-I and II transcripts and polypeptide levels were dependent on protein synthesis and decreased in the presence of cycloheximide at 3.6 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872070 TI - Chemosensitivity from the lungs of vertebrates. PMID- 7872069 TI - The role of arterial chemoreceptors in ventilatory acclimatization to hypoxia. PMID- 7872071 TI - Heymans' visit to Dublin to review "buffer" nerve experiments. PMID- 7872072 TI - A belated centennial tribute to Corneille Heymans. PMID- 7872073 TI - Glomera that are not chemosensitive? PMID- 7872074 TI - Electrotonic coupling between carotid body glomus cells. PMID- 7872075 TI - Co-binding chromophores in oxygen chemoreception in the carotid body. PMID- 7872076 TI - Actions of nicotinic agonists on isolated type I cells of the neonatal rat carotid body. PMID- 7872077 TI - Culturing carotid body cells of adult cats. PMID- 7872078 TI - Plasticity in cultured arterial chemoreceptors: effects of chronic hypoxia and cyclic AMP analogs. PMID- 7872079 TI - Carotid body chemoreception: role of extracellular Ca2+. PMID- 7872080 TI - Cytosolic calcium in isolated type I cells of the adult rabbit carotid body: effects of hypoxia, cyanide and changes in intracellular pH. PMID- 7872081 TI - Characterization of membrane currents in pulmonary neuroepithelial bodies: hypoxia-sensitive airway chemoreceptors. PMID- 7872082 TI - Ionic currents on endothelial cells of rat brain capillaries. PMID- 7872083 TI - Urokinase and its receptor: marker of malignancy? PMID- 7872084 TI - Electrochemical measurement of rapid dopamine release in perfused cat carotid body during onset of hypoxia. PMID- 7872085 TI - Hypoxia-induced catecholamine release from rat carotid body, in vitro, during maturation and following chronic hypoxia. PMID- 7872086 TI - Assessment of Na+ channel involvement in the release of catecholamines from chemoreceptor cells of the carotid body. PMID- 7872087 TI - Activation of GTP-binding proteins by aluminum fluoride modulates catecholamine release in the rabbit carotid body. PMID- 7872088 TI - Catecholamines in the rabbit carotid body: content and secretion. PMID- 7872089 TI - Oxygen sensing in the carotid body: ideas and models. PMID- 7872090 TI - Cholinergic aspects of carotid body chemotransduction. PMID- 7872091 TI - Low PO2 dependency of neutral endopeptidase and acetylcholinesterase activities of the rat carotid body. PMID- 7872092 TI - Proportional sensitivity of arterial chemoreceptors to CO2. PMID- 7872093 TI - Effects of expiratory duration on chemoreceptor oscillations. PMID- 7872094 TI - Effects of intravenous infusions of KCl and lactic acid on chemoreceptor discharge in anaesthetized cats. PMID- 7872095 TI - The effect of intravenous infusion of lactic acid on carotid chemoreceptor discharge in anaesthetized cats ventilated with room air or 100% O2. PMID- 7872096 TI - The carotid bodies as thermosensors: experiments in vitro and in situ, and importance for ventilatory regulation. PMID- 7872097 TI - Inhibition of ventilation by carotid body hypocapnia during sleep. PMID- 7872098 TI - Metabolic acid-base status and the role of carotid chemoreceptors in hyperoxic breathing. PMID- 7872099 TI - Ventilatory responses to histotoxic chemostimulation in hypoxia adapted rats. PMID- 7872100 TI - Chemoreflex sensitization augments sympathetic vasomotor outflow in awake humans. PMID- 7872101 TI - Carotid chemoreceptor control of vascular resistance in resting and contracting skeletal muscle. PMID- 7872102 TI - Effects of endothelins on respiration and arterial chemoreceptor activity in anaesthetised rats. PMID- 7872103 TI - Changes in blood glucose concentration in the carotid body modify brain glucose retention. PMID- 7872104 TI - Is the second carotid body redundant? PMID- 7872105 TI - Activity of cardiac vagal preganglionic neurones during the pulmonary chemoreflex in the anaesthetized cat. PMID- 7872106 TI - Trophic regulation of carotid body afferent development. PMID- 7872107 TI - Carotid body dopamine response to acute hypoxia in developing rabbits. PMID- 7872108 TI - Attenuation of the hypoxic ventilatory response in awake rabbit pups; possible role of dopamine. PMID- 7872109 TI - D2-dopamine receptor mRNA in the carotid body and petrosal ganglia in the developing cat. PMID- 7872110 TI - The role of endogenous dopamine as an inhibitory neuromodulator in neonatal and adult carotid bodies. PMID- 7872111 TI - Intracellular calcium responses to hypoxia and cyanide in cultured type I cells from newborn and adult rabbits. PMID- 7872112 TI - Effects of acetazolamide on the time course of the CO2 response of carotid body in the newborn kitten. PMID- 7872113 TI - Cardiovascular responses to hypoxia in developing swine. PMID- 7872115 TI - Is the rapid and intense peripheral vasoconstriction occurring during acute hypoxaemia in the llama fetus an arterial chemoreflex? PMID- 7872114 TI - Fetal reflexes in chronic hypoxaemia. PMID- 7872116 TI - Is the ventilatory decline seen in newborns during hypoxaemia centrally mediated? PMID- 7872117 TI - Postmortem changes in the human carotid body. PMID- 7872118 TI - Effects of various diseases upon the structure of the human carotid body. PMID- 7872119 TI - Modification of the rabbit carotid body type I cell mitochondria by high altitude exposure and the effects of dracocephalum heterophyllum. PMID- 7872120 TI - Breathing frequency and tidal volume are independently controlled in garter snakes: the role of CO2-rise time. PMID- 7872122 TI - The stimulus modality of the hypoxic ventilatory response in rodents. PMID- 7872121 TI - Effects of chronic hypoxia on rat carotid body and toad carotid labyrinth glomus cells. PMID- 7872123 TI - Histochemical demonstration of carbonic anhydrase in the larynx. PMID- 7872124 TI - Effects of intralaryngeal CO2 and H+ on laryngeal receptor activity in the perfused larynx in cats. PMID- 7872125 TI - The effects of airway CO2 on laryngeal pressure, 'drive' and cold receptors in spontaneously breathing cats. PMID- 7872126 TI - Laryngeal receptors are sensitive to expiratory concentrations of CO2. PMID- 7872127 TI - The effects of airway CO2 and cooling on ventilation and upper airway resistance in anaesthetized rats. PMID- 7872128 TI - The effects of laryngeal CO2 and cooling on ventilation and laryngeal resistance in the anaesthetized rat. PMID- 7872129 TI - International meetings on arterial chemoreceptors: historical perspectives. PMID- 7872130 TI - Neurotransmitters in the carotid body. PMID- 7872131 TI - Reflexes arising from the arterial chemoreceptors. PMID- 7872132 TI - Central integration of chemoreceptor afferent activity. PMID- 7872133 TI - Chemoreceptor function in the fetus and neonate. PMID- 7872134 TI - Behavior and the basal ganglia. AB - When viewed as a whole, these basal ganglia-thalamo-cortical circuits appear to play a modulating role in a wide range of behaviors. At the cortical level, given convergence upon specified regions within the frontal lobes, the behaviors in question would be those dependent upon SMA, premotor, frontal eye fields, dorsolateral, and orbitofrontal outflow targets. Broadly speaking, processes such as the generation, maintenance, switching, and blending of motor, mental, or emotional sets would be involved. Accordingly, in basal ganglia disease, the planning and the execution of the above behavioral domains can be affected. Given the diversity and complexity of activity within the basal ganglia, the consequences of disruption depend largely upon lesion site and the associated interplay of neurochemical factors. For example, in the motor domain, damage to various striatal circuitry levels can result in either hypo- or hyperkinetic disorders of movement. Following this analogy, it might also be said that diverse lesions, depending on site, can result in problems with the development and maintenance of behavioral sets ("hypophrenic") versus problems in relinquishing preferential sets ("hyperphrenic"). These contrasting patterns are best represented in PD and OCD, respectively. In the latter case, however, the "hyperphrenic" pattern would only apply to those behaviors which are part of the obsessional rituals. This suggests that procedural system "overdrive" remains domain-specific as is the case for most operations within the procedural system. To return to the broad principle of habituation, a process first described in the context of the visual system and its connections with the tail of the caudate nucleus, it would be tempting to view PD and OCD as disorders of "under" and "over" habituation to behavioral routines. Unfortunately, the situation has proven to be more complex in view of recent neuropsychological findings (Nicholson et al., in preparation). Using a variety of problem-solving and other cognitive tasks, both PD and OCD patients were found to require more practice and/or the provision of external guidelines to facilitate habit formation. Thus, in both cases, as in other disorders of the basal ganglia, the establishment of useful heuristics by which to direct adaptive behavior suffers. OCD patients therefore appear to have at least two compartmentalized types of basal ganglia dysfunction: the ritualistic compulsions and obsessions as well as the heuristic inefficiency (i.e., poor procedural mobilization). PD patients would also suffer a similar fate as it is known that the degrees of motor versus nonmotor (i.e., procedural) deficit are poorly correlated (42).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7872135 TI - Parkinson's disease: drug-induced psychiatric states. AB - Drug-induced psychiatric states occur frequently in PD. In the prelevodopa era, depression and other psychiatric disorders were described in PD, but in untreated patients psychosis was rare. Since the development of levodopa and other pharmacological treatments for PD, however, psychotic symptoms have become much more common (10-50%). In some individuals these problems can be more disabling than the motor features of PD and, as a result, pose a serious threat to the patient's ability to maintain independence. The drug-induced psychoses consist of several distinct psychiatric syndromes that can be divided broadly into those occurring on a background of a clear sensorium and those which are accompanied by confusion and clouding of consciousness. Benign organic hallucinosis is the most common of these syndromes (30%). It usually occurs on a background of a clear sensorium and may not be a particularly troublesome problem if the patient is able to retain insight into the nature of these symptoms. More disabling syndromes usually include delusional thinking that is frequently paranoid, confusion and even frank delirium. Although all these psychotic syndromes can occur in isolation, there is a tendency for mild symptoms to progress to more disabling ones if adequate and timely treatment is not instituted. Abnormal dreaming and sleep disruption often precede these difficulties by weeks to months and may provide an important early clue to their onset. The mechanisms responsible for drug-induced psychotic symptoms in PD are unknown, but dopaminergic (especially mesolimbic) and serotoninergic systems are likely to be involved. The treatment of the drug-induced psychoses in PD should be undertaken in a stepwise manner. A detailed discussion of this approach, including the use of anti-PD medication adjustment, clozapine, and other medications (neuroleptic and nonneuroleptic) and ECT is provided (see Fig. 1). Although drug-induced psychoses are the most important of the drug-induced psychiatric states, mania, anxiety, and hypersexuality may also occur. Depression is also common in PD, but it is unlikely to occur as a side effect of antiparkinsonian medications. PMID- 7872136 TI - Cognitive and behavioral changes in the Parkinson-plus syndromes. PMID- 7872137 TI - The spectrum of diseases with diffuse Lewy bodies. PMID- 7872138 TI - Psychiatric and behavioral abnormalities in Wilson's disease. AB - From the literature and our experience, a relatively consistent picture of psychiatric and behavioral abnormalities in Wilson's disease emerges. The essential elements of this picture are as follows: 1. Psychiatric and behavioral abnormalities are frequent manifestations of WD. The estimates range from 30% (18) to 100% (2) of symptomatic patients. As Wilson himself was the first to state in reference to "mental change," "its importance should not be underestimated." 2. Psychiatric and behavioral abnormalities are often the initial manifestations of WD. Two thirds of our patients first presented with psychiatric symptoms and one third received psychiatric treatment before the diagnosis of WD was made. In the early stages of the disease, when psychiatric and behavioral symptoms predominate, the diagnosis is often missed. Of our 124 patients, WD was diagnosed in only one during this phase. Until the psychiatric presentation of WD is recognized, and the disease is included in the differential diagnosis of psychiatric symptoms, its diagnosis will be missed or delayed. In our patients, and others' (13,15), the delay in diagnosis ranged from 1 to 5 years. Such a delay is particularly tragic as favorable outcome depends upon early discovery. 3. The most common of the psychiatric and behavioral manifestations of WD include: personality changes such as irritability and low threshold to anger, depression sometimes leading to suicidal ideation and attempts, deteriorating academic and work performance that is present in almost all neurologically affected patients. We (1) have also observed, as did Scheinberg and Sternlieb (2) that WD patients exhibit increased sexual preoccupation and reduced sexual inhibition. Finally, cognitive impairment, psychosis, anxiety, and other psychiatric disorders, although less frequent, also occur. 4. Some of the psychiatric and behavioral symptoms are reversible with WD specific therapy, whereas others are not. We are impressed with the frequency with which the behavioral and "cognitive" symptoms are reversed over 1 to 2 years of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872140 TI - Dementia and cognitive changes in Huntington's disease. PMID- 7872139 TI - Behavioral and psychiatric symptoms associated with Huntington's disease. PMID- 7872141 TI - Psychological effects of predictive testing for Huntington's disease. PMID- 7872142 TI - Psychopathological and cognitive correlates of tardive dyskinesia in schizophrenia and other disorders treated with neuroleptic drugs. PMID- 7872143 TI - Phenomenology and psychopathology related to psychogenic movement disorders. PMID- 7872144 TI - Disruptive behavior, hyperactivity, and learning disabilities in children with Tourette's syndrome. AB - As in many other areas of science, improvements in research methodologies lead the way to powerful new understanding of disorders and their treatment. Great strides have been made in defining the phenomenology of TS and its relationship to other disorders. However, we have not yet reached a true consensus and developed treatment strategies based on that consensus. Clearly much research needs to be done. Identifying the putative gene for TS would greatly accelerate this process. PMID- 7872145 TI - Sensory phenomena in Tourette's syndrome. AB - Sensory phenomena in the form of premonitory urges and "just right" perceptions appear to be common features of tic disorders including TS. Shapiro et al. (5) proposed that these sensory phenomena are an idiosyncratic feature of TS that is present in a minority of TS patients. However, data from recent studies suggest that premonitory urges are common in TS and may even be a defining feature of the disorder. These findings further indicate that clinicians should inquire about the presence of premonitory urges during the assessment of individuals with movement disorders. Of particular interest for future research is the relationship of the anatomical location of the premonitory urge and the site of the tic. Further study of sensory phenomena in other movement disorders is also warranted. PMID- 7872146 TI - Obsessive-compulsive disorder in Tourette's syndrome. PMID- 7872147 TI - Cognitive and behavioral changes in patients with focal lesions of the basal ganglia. PMID- 7872148 TI - Tourette's syndrome: a behavioral spectrum disorder. AB - Tourette's syndrome is a fascinating, complex, hereditary, neuropsychiatric spectrum disorder in which the tics are only one of many symptoms. Data to date suggest the mechanism of inheritance is just as complex as the disorder itself and involves the coming together of a number of common genes that affect dopamine and serotonin metabolism. Because these neurotransmitters modulate the function of many areas of the brain, the result is a wide spectrum of behavioral disorders. As such TS provides a significant challenge to the physician. Because many of the newer medications are quite effective, taking on the treatment of this challenging and complex behavioral spectrum disorder can be extremely rewarding. PMID- 7872149 TI - Tourette's syndrome: a multigenerational, neuropsychiatric disorder. PMID- 7872150 TI - Psychogenic problems associated with dystonia. PMID- 7872151 TI - The parkinsonian personality. PMID- 7872152 TI - Depression in Parkinson's disease: a biochemical and organic viewpoint. PMID- 7872153 TI - Depression in Parkinson's disease: a psychosocial viewpoint. AB - We started this chapter by examining a simple psychological model that depression was a straightforward reaction to the severity of the physical impairment of Parkinson's disease, and that the relationship between the two factors was essentially linear. Because of the progressive nature of the disease, it followed that any such relationship would also be reflected in factors such as stage of illness and duration. As seen, however, the data have consistently failed to support such a simple reactive model. Examining the equivalent literature on other physical disorders revealed a remarkably similar picture suggesting that the model is largely inadequate in general, as well as in relation to Parkinson's disease. This inadequacy, however, should not be taken as evidence that psychological factors are unimportant. Rather, it suggests only that we need a more comprehensive model linking chronic disabling illness and depression. One revision suggested by the evidence was to consider nonlinear relationships, for example, between depression and stage of illness. Adopting a broader perspective, one may suppose that the risk of depression may change over the course of disease progression. For example, at the very beginning, diagnosis and the process of coming to terms with the fact of having a progressive and disabling illness may be sufficient to cause depression. Later in the course of the illness, progressive deterioration and increasing dependency may once again provoke depression. At any stage, a rapid deterioration (from whatever level) or the development or worsening of treatment complications may cause fresh concerns and require a fresh period of adjustment. Although the depression may be similar in each of these cases, the mediating psychological factor is different. In between these times, the individual may adapt to the illness and its consequences and show less vulnerability to depression. A further modification of the model is to consider the influence of multiple factors. While any one factor may individually predict depression only weakly, in combination, they may explain the observed pattern of depression more accurately. Although little evidence is available, there is the suggestion that a combination of physical and psychological factors may provide a clearer picture of depression severity. The final, major modification suggested is to view the broad consequences of the physical disease, rather than the severity of the symptoms themselves.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7872154 TI - Early cognitive changes and nondementing behavioral abnormalities in Parkinson's disease. AB - Early cognitive changes in patients with PD are often subtle and influenced by factors that interact with the disease process, including age and age of disease onset, medication, and the specific constellation of motor symptoms. These factors notwithstanding, there is ample evidence that specific cognitive changes occur early in the course of PD. Whereas language processing deficits are infrequent, subtle changes in olfaction and contrast sensitivity have been repeatedly observed. Executive function deficits are often prominent and, as an integral part of many tasks, also influence performance on a wide range of cognitive measures. This is particularly true for memory and visuospatial dysfunction, two areas that rely heavily on executive demands. Finally, depressive symptoms are also frequent in the early stages of the disease. The significance of early behavioral changes and their prognostic implications are largely unknown and need to be assessed prospectively. PMID- 7872155 TI - Late cognitive changes in Parkinson's disease with an emphasis on dementia. PMID- 7872156 TI - Molecular basis of Fc receptor function. PMID- 7872157 TI - Interleukin-5 and its receptor system: implications in the immune system and inflammation. PMID- 7872158 TI - Human antibodies from combinatorial libraries. PMID- 7872159 TI - Immune response against tumors. PMID- 7872160 TI - Formation of the chicken B-cell repertoire: ontogenesis, regulation of Ig gene rearrangement, and diversification by gene conversion. PMID- 7872162 TI - A mandate for what? PMID- 7872161 TI - The Alabama Infected Health Care Worker Act. State Department of Public Health. PMID- 7872163 TI - Alabama Department of Public Health Policy and procedures for compliance with CDC recommendations of July 12, 1991 and Alabama's Infected Health Care Worker Management Act. PMID- 7872164 TI - HCFA's evaluation and management services: new documentation guidelines for physicians. American Medical Association and Health Care Financing Administration. PMID- 7872165 TI - Multicenter evaluation of the Strecker tantalum stent for acute coronary occlusion after angioplasty. AB - The Strecker stent is a balloon-expandable, flexible endoprosthesis constructed of knitted tantalum wire and has been implanted successfully in peripheral arteries. This study presents the first multicenter experience with implantation of this radiopaque device in the coronary arteries in 64 patients of 6591 consecutive percutaneous transluminal coronary balloon angioplasty (PTCA) procedures complicated by abrupt closure. In all except 1 patient the stents (n = 72) were correctly placed, and flow could be reestablished immediately. During hospitalization 12 (19%) patients had stent closures; 5 (8%) patients had Q-wave myocardial infarctions; and 13 (20%) patients underwent bypass surgery (4 on an emergency basis). The in-hospital mortality was 9%: 2 patients died after thrombotic stent occlusions; 2 patients had fatal bleeding complications; and 2 patients died after bypass surgery. Major bleeding complications at the puncture site were observed in 8 (12.5%) patients. Angiograms (n = 45) after 17 +/- 5 weeks revealed a stent patency rate of 89%. Thus the Strecker coronary stent proved to be helpful in the management of acute vessel closure during PTCA. However, in this first series a high incidence of early thrombotic occlusions and bleeding complications warrants close anticoagulation monitoring and limits broader indications. PMID- 7872166 TI - Distal embolization is common after directional atherectomy in coronary arteries and saphenous vein grafts. AB - Coronary embolization is a complication of coronary intervention procedures. The incidence, predictors, and clinical significance of this phenomenon during directional atherectomy were examined in 111 consecutive patients who underwent directional atherectomy to 120 lesions. Distal embolization occurred in 31 (28%) of the patients. It was noted mainly in the saphenous vein graft group of patients (12 [48%] of 25) versus the native coronary group (19 [22% of 86]; p = 0.01). Clinical predictors were age and de novo lesions. Morphologic predictors were larger artery size, larger postprocedure minimal luminal diameter, calcific lesions, and type C lesions. The only difference in clinical outcome was a longer hospitalization in the distal embolization group with 3.9 +/- 3.7 days versus the rest of the patients 2.4 +/- 2.4 days (p = 0.01). In the majority of patients there was no significant adverse clinical outcome. PMID- 7872167 TI - Follow-up patency of side branches covered by intracoronary Palmaz-Schatz stent. AB - To assess the risk of late side branch occlusion after Palmaz-Schatz stent deployment, we analyzed the angiographic evolution of 62 patients treated by successful stent implantation who had a total of 85 side branches starting from the stented segment. Side branches were considered minor (n = 39) when the diameter was < 1 mm and intermediate (n = 46) when the vessel had > or = 1 mm diameter. One angiographic follow-up study was available in all patients at 8 +/- 5 months. Eight minor branches presented some degree of stenosis at origin before stent deployment (4 totally occluded). After stent deployment, 32 (82%) of 39 remained unchanged and 3 became occluded. Late progression at origin occurred in 4 of 34 (3 occluded). Before stent deployment, 48% of the intermediate branches had some compromise degree at their starting point (1 totally occluded). Eight of 45 intermediate branches became occluded after stent implantation. Late progression at origin happened in 5 of 32 branches (2 occluded). Some degree of follow-up stenosis regression at the origin was observed in 22 (26%) of 85 arteries. Neither clinical nor angiographic factors could be identified as predictors of late side branch occlusion or stenosis progression at its origin. Later occlusion or progression at origin of a side branch covered by a Palmaz Schatz stent seems to be an uncommon occurrence (7% and 12% respectively) that cannot be predicted by angiographic or clinical factors. On the contrary, regression at follow-up of a side branch-origin stenosis can also come about. PMID- 7872168 TI - Long-term angiographic follow-up of lesions patent 6 months after percutaneous coronary angioplasty. AB - To determine long-term angiographic prognosis after successful angioplasty (< 50% residual stenosis, > or = 20% reduction of stenosis, and no major complications), coronary angiography was performed 2 to 4 years after angioplasty in patients who were < or = 70 years old at the time of treatment and who showed patency (< or = 50% stenosis) 6 months after the initial procedure. Among 407 lesions that were dilated in 333 patients between 1983 and 1989, 298 (73.2%) lesions were reviewed by long-term angiography after 177 +/- 34 weeks. At long-term follow-up, 4 (1.3%) lesions were totally occluded, 3 (1.0%) had severe stenosis (> or = 75% stenosis), 9 (3.0%) had mild stenosis (> 50% to < 75% stenosis), and 282 (94.6%) were patent (< or = 50% stenosis). The percentage of stenosis of patent lesions decreased from 24% +/- 14% at 6 months to 21% +/- 13% at long-term follow-up (p < 0.0001). No specific clinical or angiographic characteristics were identified in patients with severe stenosis at long-term follow-up. These findings indicate that when patency is obtained 6 months after angioplasty, a 95% long-term patency rate with regression of stenosis can be expected. PMID- 7872169 TI - Increase of neutrophil adhesion and vasoconstriction with platelet deposition after deep arterial injury by angioplasty. AB - Physiopathologic events after arterial injury are largely influenced by blood element reactions with the injured surface. To determine acute arterial reactivity to injury, simultaneous chromium 51-labeled platelet deposition and indium 111-labeled neutrophil adhesion were quantified at the site of different degrees of carotid arterial injury by balloon dilatation in 21 normal pigs. The degree of vasoconstriction distally to the dilated areas was also quantified angiographically. Arteries were classified histologically as (1) uninjured with intact endothelium; (2) mildly injured with endothelial desquamation; or (3) deeply injured with lesions extending beyond internal elastic lamina, exposing the media. We found that, compared to mild injury, deep injury was associated with greater platelet deposition (38.2 +/- 5.7 x 10(6)/cm2 vs 7.8 +/- 0.9 x 10(6)/cm2; p < 0.05), neutrophil adhesion (30.6 +/- 4.1 x 10(4)/cm2 vs 10.2 +/- 2.9 x 10(4)/cm2; p < 0.05), and vasoconstrictive response (45.5% +/- 3.2% vs 26.7% +/- 2.8%; p < 0.05). Although distally to both types of injuries, noninjured arterial segments with intact endothelium were thromboresistant to platelet deposition, neutrophil adhesion to intact endothelium was much higher after deep injury (2.2 +/- 0.4 x 10(4)/cm2) compared to mild injury (0.36 +/- 0.1 x 10(4)/cm2; p < 0.05). Like platelet deposition, neutrophil adhesion is influenced by the severity of arterial injury; both may therefore be implicated in thrombogenesis and vascular responsiveness after arterial injury in vivo. PMID- 7872170 TI - Limited value of exercise testing in the detection of silent restenosis after successful coronary angioplasty. AB - We studied the diagnostic value of exercise electrocardiographic (ECG) testing in 191 patients who were completely asymptomatic 6 months after a successful percutaneous transluminal coronary angioplasty procedure. With > 70%- and > 50% diameter stenosis at follow-up as restenosis criteria, the sensitivities of exercise ECG testing were 29% and 21%; the specificities 89% and 91%; the positive predictive values 20% and 52%; the negative predictive values 93% and 70%; the accuracies 83% and 68%; and the risk ratios 2.8 and 1.7, for prevalences of 9% and 33%, respectively. There were no significant differences in the diagnostic value of exercise ECG testing between men and women, patients receiving or not receiving beta-blocking agents, and the presence or absence of pathologic Q waves. Significant differences in systolic blood pressure and the rate-pressure product at peak exercise were found between patients with and without restenosis. For individual patients, however, no practical conclusions can be drawn from these values. In conclusion, the diagnostic value of exercise ECG testing for silent restenosis is low, and supplementation with other techniques seems to be warranted. PMID- 7872171 TI - Left ventricular performance during exercise testing in patients with silent and symptomatic myocardial ischemia. AB - We compared cardiohemodynamic response to dynamic exercise in 32 patients with exercise-induced silent or symptomatic myocardial ischemia. All patients had coronary artery disease without prior myocardial infarction and left ventricular hypertrophy. Patients underwent supine leg-exercise testing and received right heart catheterization. All patients exhibited ischemic ST-segment depression on electrocardiogram during exercise testing. They were classified retrospectively into two groups according to the absence (n = 10, group 1) or presence (n = 22, group 2) of chest pain induced by exercise. There was no significant difference between groups in the magnitude of peak ST-segment depression. Pulmonary artery wedge pressure at peak exercise was significantly lower (p < 0.01), and the cardiac index was significantly higher (p < 0.01), in group 1 versus group 2. Our results indicate that exercise-induced left ventricular dysfunction is less severe in patients with silent myocardial ischemia than in those with symptomatic ischemia. PMID- 7872172 TI - Significance of silent myocardial ischemia during exercise testing in women: report from the Coronary Artery Surgery Study. AB - To evaluate the significance of silent myocardial ischemia during exercise testing in women compared to men, we analyzed the data on 1087 women and 3834 men who underwent exercise testing and coronary angiography from the Coronary Artery Surgery Study (CASS) registry. The patients were divided into three groups on the basis of the results of exercise testing: group 1, silent ischemia (253 women, 853 men); group 2, symptomatic ischemia (156 women, 1250 men); and group 3, no ischemia (678 women, 1731 men). The survival rate at 12 years for women was 80% for group 1, 75% for group 2, and 86% for group 3 (p = 0.0022); the survival rate for men was 69% for group 1, 69% for group 2, and 76% for group 3 (p < 0.001). In both men and women with silent ischemia, the 12-year survival rate was related to the severity of coronary artery disease (CAD) and ranged from 79% for women with one-vessel CAD to 46% for men with three-vessel CAD. Survival at 12 years was enhanced by coronary artery bypass graft surgery as compared to medical treatment in patients with silent ischemia and three-vessel CAD for men (61% vs 46%, respectively, p = 0.0014) but not for women (45% vs 50%, respectively, p = 0.98). These data suggest that silent ischemia in women and men adversely affects survival rate and that men may gain more benefit from coronary artery bypass graft surgery than women when three-vessel CAD is present. PMID- 7872173 TI - Coronary arteriography for quantitative analysis: experimental and clinical comparison of cinefilm and video recordings. AB - Although use of videotape for the recording of coronary angiograms continues to grow, the validity of quantitative coronary angiographic analysis of video images remains unknown. To estimate the reliability of angiographic images recorded on videotape, experimental and clinical angiograms were recorded simultaneously on both 35 mm cinefilm and super-VHS videotape with normal images and with spatial filtering of the images (edge enhancement) on a digital cardiac imaging system. The experimental angiographic studies were performed with plexiglass blocks and stenosis phantom of 0.5 to 3.0 mm in diameter. The clinical angiograms were recorded in 20 patients undergoing percutaneous transluminal coronary angioplasty (31 frames before and 20 frames after percutaneous transluminal coronary angioplasty). The cinefilm and corresponding videotapes were analyzed off-line with the new version of the coronary angiography analysis system. For the experimental study, measurements of minimal luminal diameter obtained from cinefilm, normal-image videotape, and edge-enhanced videotape were compared with the true phantom diameter. In the clinical study the agreement between measurements obtained from cinefilm and measurements from normal-image videotape and edge-enhanced videotape was examined. In the phantom series the accuracy and precision of quantitative coronary angiography measurement for cinefilm were 0.10 +/- 0.08 mm, for normal-image videotape -0.11 +/- 0.18 mm, and for edge enhanced videotape -0.10 +/- 0.11 mm (mean +/- SD). In the clinical series, the differences between measurements from cinefilm and normal-image videotape were 0.14 +/- 0.20 mm and from cinefilm and edge-enhanced videotape 0.04 +/- 0.13 mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872174 TI - Detection of alterations in left ventricular fatty acid metabolism in patients with acute myocardial infarction by 15-(p-123I-phenyl)-pentadecanoic acid and tomographic imaging. AB - 15-(p-iodine 123-phenyl)-pentadecanoic acid (IPPA) is a synthetic radiolabeled fatty acid with kinetics similar to palmitate. Fourteen patients who had had an acute myocardial infarction 7 +/- 6 days earlier and 9 normal volunteers were studied after being injected with IPPA. The volunteers were remarkable for homogeneous uptake and metabolism of IPPA; 13 of 14 infarct patients showed areas of decreased uptake > 2 SDs below the mean of the volunteers. Metabolism was homogeneous in the volunteers (14.2% +/- 5.8%) and was significantly higher than in regions identified as infarcted (3.9% +/- 12.1%, p < 0.001). Noninfarcted regions in the patients demonstrated significantly increased rates of IPPA metabolism compared to rates in volunteers (23.0% +/- 9.6% p < 0.001). We conclude that patients with recent myocardial infarction have abnormalities of fatty acid metabolism such as decreased uptake and clearance of fatty acid in regions of infarction and normal uptake but relatively increased fatty acid clearance in unaffected regions of the myocardium. PMID- 7872175 TI - Four- versus 6-minute infusion protocol for adenosine thallium-201 single photon emission computed tomography imaging. AB - Intravenous adenosine infusion results in immediate maximal coronary arteriolar vasodilatation. Side effects occur in most patients who receive adenosine. For these reasons, a shorter infusion for pharmacologic stress thallium-201 testing may improve patient tolerability without compromising diagnostic accuracy. In a retrospective, unblinded evaluation, we compared side effects and accuracy of a standard 6-minute adenosine infusion single photon emission computed tomography (SPECT) study with a 4-minute protocol in 730 and 621 patients, respectively. Adenosine was infused at 140 micrograms/kg/minute in both groups; thallium-201 was injected at the 3-minute mark of the 4-minute protocol and at the 4-minute mark of the 6-minute protocol. Angiographic follow-up (mean 8 days) after thallium-201 testing was available in 233 (32%) of the patients in the 6-minute protocol and in 174 (28%) of the patients in the 4-minute protocol (p not significant (NS). Side effects occurred in 90% of the patients in the 6-minute protocol and in 91% of the patients in the 4-minute protocol (p = NS). Premature termination of the infusion was required in 4% of the patients in the 6-minute protocol and 2% of the patients in the 4-minute protocol (p = 0.02). Second- or third-degree atrioventricular block was noted in 4.5% and 3.0% of the 6- and 4 minute groups, respectively (p = NS). The duration of symptoms averaged 2.9 +/- 4.4 minutes in the patients in the 6-min protocol and 2.1 +/- 1.6 minutes in the patients in the 4-minute protocol (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872176 TI - Relation between insecurity and Type A behavior. AB - This article presents a new Type A Videotaped Clinical Examination scale that measures insecurity. This scale was validated against an existing insecurity measure in a sample of 204 individuals. The results indicated that this new scale is a valid measure of insecurity. The relation between insecurity and type A behavior was examined in a sample of 3013 people. In this large population insecurity showed a strong positive correlation to type A behavior and to each of the two overt behavioral components, time urgency and free-floating hostility. PMID- 7872177 TI - Outcome of patients with nonsustained ventricular tachycardia and severely impaired ventricular function who have negative electrophysiologic studies. AB - Twenty-nine consecutive patients with a prior myocardial infarction, severely reduced left ventricular ejection fraction (26% +/- 8%), and asymptomatic nonsustained ventricular tachycardia were enrolled in a prospective trial. After a negative programmed electric stimulation study (3 extrastimuli at 2 sites with 2 drive trains), the 26 men and 3 women (mean age 71) were monitored for a mean of 13 months without antiarrhythmic drug therapy. Five patients died suddenly or had sustained ventricular tachycardia; three others had a cardiac, nonarrhythmic death. Events occurred in the first 13 months of the surveillance period. Clinical factors associated with a poor outcome included congestive heart failure and lack of beta-blocker therapy. In addition, patients with events tended to have lower ejection fractions than those without (21% vs 28%, p not significant). Thus a negative programmed electric stimulation study does not necessarily imply a benign outcome in patients with a prior infarction and nonsustained ventricular tachycardia if they also have severe left ventricular dysfunction and a history of heart failure. These data have important implications for the design and conduct of contemporary clinical trials. PMID- 7872178 TI - Prediction of electrophysiologic study results in patients treated with amiodarone. AB - To identify whether electrophysiologic study results during early-phase amiodarone therapy can be predicted by previous electrophysiologic study, we reviewed the electrophysiologic data of 50 patients with inducible sustained ventricular arrhythmias who underwent 4.3 +/- 1.3 drug trials before being given amiodarone. Study results during testing with agents of the modified Vaughan Williams Ia classification were compared with data obtained after 2 weeks of amiodarone therapy. Partial response by electrophysiologic study was defined as well-tolerated ventricular tachycardia < 150 beats/min associated with a blood pressure > or = 90 mm Hg. Significant slowing in the rate of induced ventricular tachycardia was seen during therapy with both Ia agents and amiodarone, although there was a trend toward greater slowing during amiodarone treatment (180 +/- 45 beats/min vs 164 +/- 65 beats/min; p = 0.09). Two of three patients with noninducible ventricular tachycardia during amiodarone showed profound ventricular tachycardia slowing during Ia therapy. Thirty-eight of 50 patients demonstrated concordance of electrophysiologic study results with regard to achieving partial response criteria. Twenty patients died during a mean follow-up period of 37 +/- 29 months; 7 of the 10 sudden deaths occurred in patients who did not meet partial response criteria. We conclude that patients with inducible sustained ventricular arrhythmias failing serial drug testing with Ia agents only rarely have their ventricular tachycardia suppressed during amiodarone therapy. Partial response criteria are often concordant between testing on agents of the Ia classification and amiodarone, and there was no significant difference in survival in patients based on their partial response status. PMID- 7872179 TI - Immediate and late outcome of percutaneous balloon mitral valvotomy in patients with significantly calcified valves. AB - We assessed immediate and late outcome in 55 patients with significantly calcified valves (group 1) after balloon mitral valvotomy and compared the results with those from 60 patients with noncalcified or minimally calcified valves (group 2). After valvotomy, mitral valve area increased from 1.03 +/- 0.30 cm2 to 1.64 +/- 0.35 cm2 (p = 0.0001) by echo planimetry in group 1 but was significantly smaller than the mitral valve area in group 2 after valvotomy (1.94 +/- 0.38 cm2; p = 0.0001). At a mean follow-up period of 30 months (range 2 to 81 months), 51% of patients in group 1 and 83% in group 2 were symptom free (p = 0.0002). In group 2, 15 (27%) patients and in group 2, 4 (7%) patients had cardiac events (p = 0.003). The risk ratio for cardiac events was 4.3 times greater in group 1 than in group 2. In group 1, the risk ratio for cardiac events was 3.2 times higher in patients age > or = 65 years and in patients with atrial fibrillation. The 6-year cumulative cardiac event-free survival rate was 64% in group 1 and 90% in group 2 (p = 0.005). In 75 (65%) patients who had follow-up echocardiographic study (35 in group 1 and 40 in group 2), mitral valve area decreased to 1.48 +/- 0.42 cm2 at follow-up in group 1 (p < 0.01) and to 1.77 +/- 0.50 cm2 in group 2 (p = 0.3). Restenosis occurred in 16 (46%) of 35 patients in group 1 and 10 (25%) of 40 in group 2 (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872180 TI - Transesophageal echocardiographic evaluation of cor triatriatum in children. AB - Four children with cor triatriatum underwent intraoperative transesophageal echocardiography. Two patients had cor triatriatum alone and two had associated complex congenital heart disease. Transesophageal echocardiography provided optimal imaging of these defects and provided unique information that facilitated surgical management in these children. PMID- 7872181 TI - Five-year follow-up study of the prevalence and progression of pulmonary hypertension in systemic lupus erythematosus. AB - The purpose of this study was to determine the prevalence and progression of pulmonary hypertension over a 5-year follow-up period in 28 patients with systemic lupus erythematosus (SLE) who were originally enrolled in an echocardiographic study of pulmonary hypertension in 1985 and 1986. Twenty healthy volunteers without cardiac or pulmonary disease participated as normal controls. Each patient and control underwent a complete Doppler echocardiographic study. Doppler echocardiographic recordings of tricuspid insufficiency, with saline contrast enhancement when necessary, were used to calculate pulmonary artery systolic pressure according to the modified Bernoulli equation. Doppler echocardiographic measurement of cardiac output was performed at rest for each subject, and pulmonary resistance was calculated by dividing the pulmonary artery systolic pressure by the cardiac output. These results were compared to results of the original studies to detect serial changes in pulmonary pressure and pulmonary resistance; results were also compared to the group of normal controls. The prevalence of pulmonary hypertension increased from 14% at the first study to 43% at follow-up. A significant increase in mean systolic pulmonary artery pressure was detected in the SLE patients during the follow-up period: 23.4 vs 27.5 mm Hg (p < 0.005). In addition, a significantly higher pulmonary artery pressure was detected in the SLE patients compared with the normal controls (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872182 TI - Angiographic predictors of new coronary occlusions. AB - To determine whether coronary angiography is predictive of the future site of coronary occlusion, we analyzed the coronary angiograms of 246 consecutive patients having two or more angiograms without therapeutic invasive intervention in the interval between angiograms. The average interval between studies was 46 months. Of 2183 normal segments at the first angiogram, 51 (2.3%) were occluded at the second angiogram, whereas in segments with minimal disease (1% to 25% diameter stenosis) 33 (8%) of 411 were occluded (p < 0.05). There was a further stepwise increase in the occlusion ratio, with increasing stenosis reaching a 31% occlusion ratio in lesions with critical (91% to 99%) stenosis at the first angiogram. For any given degree of stenosis, the occlusion ratio of "long" lesions (5 to 20 mm) was on the average more than twice that of "short" lesions (< 5 mm, p < 0.01), except in lesions with critical stenosis (91% to 99%) where length was no longer important. Occlusion of segments judged free of disease on the first angiogram was highest in the right coronary artery, 4.7%, versus 2.7% in the left anterior descending and 0.6% in the circumflex artery (p < 0.01). History of recent myocardial infarction was a good clinical predictor of occlusion and deterioration of ventricular function. PMID- 7872183 TI - Low-dose dobutamine echocardiography predicts the early response of dysfunctioning myocardial segments to coronary artery bypass grafting. AB - Dobutamine echocardiography has recently been introduced for use in identification of viable myocardium in patients with acute myocardial infarction and prediction of the response of dysfunctioning myocardial segments to coronary angioplasty. The aim of this study was to evaluate whether this test may be used to predict the early response of dysfunctioning myocardial segments to surgical revascularization. We studied 30 patients with three-vessel disease and chronic, stable angina pectoris during coronary artery bypass grafting (CABG). Patients were monitored by intraoperative transesophageal echocardiography in the transgastric short-axis view at the papillary muscle level. The left ventricle was divided into eight segments; and 240 myocardial segments were analyzed. Percentage of systolic wall thickening (PSWT) was calculated in each segment at baseline (early after pericardiectomy), before bypass during dobutamine infusion (5 micrograms/kg/min), and after separation from cardiopulmonary bypass. Segments showing PSWT < 30% at baseline were considered dysfunctional. Segments showing an increase in PSWT > 10% during dobutamine infusion were considered responders. Segments showing an increase in PSWT < 10% during dobutamine infusion were considered nonresponders. At baseline, 161 (67%) of 240 segments had PSWT < 30% (dysfunctioning segments). During dobutamine, 98 (60%) of these segments increased PSWT > 10% (from 11.3% +/- 7.6% to 24.2% +/- 12.0%, p < 0.01; responder segments), and 63 (40%) increased PSWT < 10% (from 10.2% +/- 4.9% to 8.3% +/- 5.5%, p value not significant [NS]; nonresponder segments).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872184 TI - Amlodipine in chronic stable angina: results of a multicenter double-blind crossover trial. AB - The efficacy and safety of amlodipine, 10 mg, a new long-acting calcium antagonist, was compared with placebo in 103 patients with stable angina pectoris in a multicenter double-blind crossover study. The trial consisted of an initial 2-week single-blind placebo period followed by a first period of 4 weeks of double-blind therapy, which was followed by a 1 week washout period and then a second 4-week double-blind period after treatments were crossed over. Twenty-four hour Holter electrocardiographic monitoring was carried out in 12 patients at three centers. In the first double-blind period amlodipine produced a significantly greater increase in symptom-limited exercise duration (amlodipine 478.5 to 520.6 vs placebo 484.6 to 485.2 seconds; change +8.8% vs +0.1%, respectively; p = 0.0004) and total work (amldipine 2426 to 2984 vs placebo 2505 to 2548 kilopondmeters; change +24% vs +1.7%, respectively; p = 0.0006) and a decrease in angina attack frequency (from 3 to 1 per week; p = 0.016) and nitroglycerin consumption (from 2 to 0.5 tablets/wk; p = 0.01) compared with placebo. Holter monitoring revealed significant reductions in numbers (amlodipine 4.65 to 2.22 vs placebo 1.84 to 1.54; change -52% vs +84%, respectively; p = 0.06), absolute total area (amlodipine 87.66 to 11.43 vs placebo 5.76 to 35.24; change -87% vs +513%, respectively; p = 0.02), and duration (amlodipine 12.29 to 2.95 vs 1.66 to 7.74 seconds; change -76% vs +367%, respectively; p = 0.008) of ST-segment depressions after treatment with amlodipine compared with placebo. After the treatments were crossed over changes continued to favor amlodipine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872185 TI - Prospective, randomized, placebo-controlled, double-blind, multicenter study of exercise with enoxaparin pretreatment for stable-effort angina. AB - In this double-blind, placebo-controlled, multicenter trial, we examined the combined effects of repeated exercise and intravenous enoxaparin (low-molecular weight heparin) on treadmill exercise capacity and angiographic collateral growth and compared them with the effect of repeated exercise with placebo. Fifty-two patients with stable-effort angina were randomly assigned to receive one of two doses of enoxaparin (40 or 60 mg) or placebo. In each patient, 20 treadmill exercise sessions were performed with the pretreatment of enoxaparin or placebo for 2 to 3 weeks. Before and after treatment, coronary cineangiography was repeated to evaluate the changes in coronary and collateral circulation. Improvement of rate-pressure product (RPP) at the onset of angina was taken as an index of enhanced collateral flow reserve. Although the mean differences in the magnitude of increase in RPP were not significantly different between the 3 groups, a heterogeneous response was observed: 1620 beats/min.mm Hg in 40 mg (p = 0.12), 3060 beats/min.mm Hg in 60 mg (p = 0.02), and 1090 beats/min.mm Hg in placebo (p = 0.44). The end-points of the exercise test were changed from chest discomfort to leg fatigue or dyspnea in 10 (28%) of 36 enoxaparin-treated patients but in only 1 (6%) of 16 placebo patients (p = value not significant (NS)). Similarly, the extent of coronary and collateral circulation to the completely obstructed coronary artery was increased in 17 (47%) of 36 enoxaparin treated patients but only in 4 (25%) of 16 placebo patients (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872186 TI - QRS prolongation as an indicator of risk of ischemia-related ventricular tachycardia and fibrillation induced by exercise. AB - The majority of patients with serious ventricular arrhythmias induced by exercise have ischemic heart disease. These arrhythmias, however, develop only in a minority of the patients with coronary artery disease. The aim of this study was to investigate whether patients with ventricular tachycardia or fibrillation produced by exercise-induced ischemia exhibit any premonitory electrocardiographic indicators of arrhythmia propensity and whether arrhythmia suppression by myocardial revascularization abolished these changes. High-quality exercise electrocardiograms (50 mm/sec) from 30 case patients with ventricular tachycardia and fibrillation produced by exercise-induced ischemia were studied before and after surgical revascularization. These results were compared with those obtained from 30 control patients matched for age, sex, heart disease, and preoperative exercise capacity. The resting and peak exercise electrocardiograms were examined separately in a blinded manner with respect to QRS duration, ST segment depression, and JT intervals. Patients with bundle branch block patterns were excluded. The QRS duration at rest was similar in case and control patients preoperatively and increased significantly with exercise in both groups. However, the QRS prolongation was larger in the case group, in which it was 11 +/- 3 msec compared with 4 +/- 2 msec in the control group (p = 0.043). QRS prolongation > or = 15 msec predicted ischemia-related ventricular arrhythmias in 73% of the patients. After surgical revascularization, there was no QRS prolongation with exercise in either group. In both groups, the QRS prolongation was associated with significant ST-segment depression, which was larger in the case patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872187 TI - Effects of the potassium channel blocking agent ambasilide on ventricular arrhythmias induced by acute myocardial ischemia and sympathetic activation. AB - The ineffectiveness of traditional antiarrhythmic agents in preventing sudden cardiac death has increased the interest in drugs that prolong refractoriness. Ambasilide is a new potassium channel blocking agent that appears to prolong refractoriness at short and long cycle lengths. We assessed the effects of ambasilide, 5 mg/kg intravenous (i.v.) bolus plus 5 mg.kg-1.hr-1 i.v. infusion, in 16 anesthetized cats in which ventricular arrhythmias could be induced reproducibly by the combination of acute myocardial ischemia and increased sympathetic activity. Ambasilide decreased heart rate and blood pressure and prolonged QRS duration (26%, p < 0.05), QTc (17%, p < 0.0001), and JTc (16%, p < 0.005). Ambasilide also shifted the strength-interval curve for ventricular refractoriness by 17 to 22 msec to the right (p < 0.001). Ventricular fibrillation was observed in 7 animals and never occurred after ambasilide (p < 0.001); however, 4 (57%) of these cats had sustained ventricular tachycardia requiring cardiac massage. Ambasilide prevented nonsustained ventricular tachycardia in 2 (40%) of 5 animals. The antiarrhythmic effect of ambasilide persisted when heart rate was kept constant by atrial pacing. In no case was proarrhythmia observed. Ambasilide had a significant electrophysiologic effect at the ventricular level in the cat because it did prolong QTc and ventricular refractoriness. Therefore ambasilide showed an antifibrillatory effect but provided only a partial protection against lethal arrhythmias induced by acute myocardial ischemia and sympathetic activation. PMID- 7872188 TI - Risk of arterial embolization in 224 patients awaiting cardiac transplantation. AB - Of patients awaiting cardiac transplantation, 10% to 20% die before a donor heart becomes available. Embolization of left ventricular thrombus is a source of morbidity and mortality in this population. To define the incidence and possible risk factors for systemic arterial embolization, we examined the frequency of arterial embolic events and their relation to clinical, hemodynamic, and echocardiographic variables in 224 consecutive outpatients awaiting cardiac transplantation (left ventricular ejection fraction 0.20 +/- 0.07 and left ventricular end-diastolic dimension 76 +/- 11 mm). Over a follow-up period of 301 +/- 371 days, during which 82 (37%) patients received warfarin, arterial embolization occurred in 6 (3%) patients, 1 of whom was receiving and 5 of whom were not receiving warfarin (difference not specifically significant). The risk of embolization was not statistically different in patients with atrial fibrillation, previous embolization, or left ventricular thrombus on transthoracic echocardiogram, regardless of warfarin therapy. Cumulative risk of sudden death was similar for patients with or without echocardiographically documented left ventricular thrombus. Nonfatal bleeding complications associated with warfarin therapy occurred in 2 (2%) patients. Thus in patients who are awaiting cardiac transplantation and who receive anticoagulation therapy for left ventricular thrombus, atrial fibrillation, or previous arterial embolization, the incidence of clinically detectable arterial embolization is low despite severe ventricular dilatation. Embolization is not likely a major cause of sudden death or morbidity in this population. PMID- 7872189 TI - Echocardiographic left ventricular systolic function and volumes in young adults: distribution and factors influencing variability. AB - Low left ventricular ejection fraction (LVEF), a measure of global systolic left ventricular dysfunction, is associated with an increased risk of recurrent coronary events or death in persons with cardiac disease. There are few data on the distribution of resting LVEF and component volumes in healthy young adults or on any association of LVEF with coronary risk factors. LVEF and left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV, respectively) were measured by two-dimensional echocardiography in 1782 men and women 23 to 35 years old without self-reported heart disease (other than mitral valve prolapse, n = 53) who were participants in the multicenter Coronary Artery Risk Development in Young Adults study. Factors analyzed as potential contributors to LVEF, LVEDV, and LVESV included age, gender, race, blood pressure, alcohol use, current smoking, family history of myocardial infarction, total and high-density lipoprotein cholesterol concentrations, obesity, reported physical activity, and fitness as assessed by treadmill exercise testing. LVEF was lower in men (mean 62.6% SD 5.7%) than in women (mean 63.9%, SD 5.7%) (p < 0.01) but did not differ significantly between black and white subjects. Ninety percent of subjects had an LVEF between 53% and 71%. LVEDV and LVESV were > 25% greater in men than in women. From multivariate analysis, male gender, history of hypertension, and current smoking were each positively and independently associated with an approximately 1% lower LVEF. Body surface area, a family history of premature myocardial infarction, and treadmill workload 150 time were positively related, whereas total skinfold thickness was negatively related to LVEDV and LVESV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872190 TI - Cardiac transplantation for the cardiologist not trained in transplantation. AB - This review focuses on selected aspects of the treatment of patients being evaluated for and undergoing cardiac transplantation. Cardiac transplantation is a potential therapeutic option for a variety of irreversible cardiac disorders when the symptomatic status and anticipated survival after transplantation exceeds that of the patient's condition. The timing of cardiac transplantation with respect to prognosis is aided by the measurement of baseline hemodynamics and maximal aerobic capacity. Major cardiac problems that occur after transplantation include an increased early risk of acute allograft rejection and, later, the occurrence of allograft coronary artery disease. Furthermore, cardiac transplant recipients have unique "normal" physiologic alterations with respect to intracardiac hemodynamics, exercise capacity, the effects of denervation, and expected electrocardiographic and echocardiographic findings. PMID- 7872191 TI - Design and initial testing of an ultrasound-guided directional atherectomy device. AB - Directional atherectomy removes plaque in a targeted portion of a vessel wall. In practice, orienting the cutter toward maximal plaque accumulation and assessing the depth of vessel excision is difficult with angiographic guidance alone. Accordingly, we designed and tested a prototype catheter that combines ultrasound imaging capability with directional atherectomy in a single device. Twenty-seven in vitro vessels (32 lesions) were treated with atherectomy alone or with atherectomy combined with ultrasound. Lesion characteristics before and after the procedure were similar in each group. A significant decrease in the incidence of subintimal tissue excision was observed in the atherectomy-ultrasound group (21.1%) compared to the group that had debulking with atherectomy alone (54.5%). In addition, among specimens with media and/or adventitia the relative amount of subintimal tissue was significantly less (p < 0.001) with ultrasound guidance than with atherectomy alone (11.2% +/- 10.1% vs 34.2% +/- 8.5%). We conclude that ultrasound-guided directional atherectomy is technically feasible and may aid in achieving maximal plaque debulking and reduce the amount of subintimal injury. PMID- 7872192 TI - Intracardiac echocardiography without fluoroscopy: potential of a balloon-tipped, flow-directed ultrasound catheter. AB - Intracardiac echocardiography is a technique that uses catheter-based ultrasound transducers placed within the heart to image cardiac structures. One disadvantage to this technique is that it requires fluoroscopy for catheter placement. This study was performed to evaluate a prototype balloon-tipped, flow-directed catheter for use during intracardiac echocardiography in seven dogs. With the balloon deflated, the catheter could not be successfully advanced without fluoroscopy. Even with fluoroscopic imaging, catheter advancement was often difficult. With the balloon inflated, it could easily be passed into the pulmonary artery without fluoroscopy in 12 of 14 attempts. Images of the cardiac chambers, valves, and pulmonary artery could be obtained. In conclusion, use of a balloon-tipped, flow-directed catheter for intracardiac echocardiography and pulmonary artery imaging can be performed without the use of fluoroscopy. With continued refinements, such as enhancement of the visual field, intracardiac echocardiography could possibly be performed at the bedside to assess cardiac function or assist with interventional procedures. PMID- 7872193 TI - Nitric oxide donors in the treatment of cardiovascular and pulmonary diseases. AB - NO has been shown to be a biologic substance important to normal physiologic functioning. It appears to be an endogenous vasodilator and is involved in hemostasis and inflammation. Endothelial cell dysfunction often leads to diminished NO production; this reduction in NO concentrations may be an etiologic factor in systemic hypertension, myocardial and splanchnic ischemia, atherosclerosis, CHF, and pulmonary vascular disease. A new class of drugs, NO donors, have potential utility in the treatment of coronary and pulmonary arterial diseases. Their major advantage over nitrates and nitroprusside is a lack of pharmacologic tolerance. Clinical trials with drugs of this class are now in progress. PMID- 7872194 TI - Radiofrequency catheter ablation of an atriofascicular connection guided by direct recording of a Mahaim potential. PMID- 7872195 TI - Mechanical treatment of atrial fibrillation: removal of pericardial cyst by thoracoscopy. PMID- 7872196 TI - Balloon dilatation of stenosed pulmonary venous atrium after the Senning procedure. PMID- 7872197 TI - Migration of paradoxic embolus through a patent foramen ovale diagnosed by echocardiography: successful thrombolysis. PMID- 7872198 TI - Use of intravascular Doppler ultrasonography to assess the hemodynamic significance of the coronary-subclavian steal syndrome. PMID- 7872199 TI - Comparison of Chagas' heart disease to arrhythmogenic right ventricular cardiomyopathy. PMID- 7872200 TI - Equal vibrotactile sense thresholds of the fingers and its diagnostic significance for hand-arm vibration syndrome. AB - The vibrotactile sense thresholds (VSTs) of the middle fingers of 60 healthy persons and 97 patients with Hand-Arm Vibration Syndrome (HAVS) or subclinical HAVS were measured quantitatively. Intermittent vibratory irritations were adopted, with vibration stimulus frequencies at 8, 16, 31.5, 63, 125, 250, and 500 Hz. The equal VST contours of the fingers were mapped. Results showed that the VSTs of the normal group were not correlated with sex or handedness. From 8 Hz to 250 Hz the equal VST contours of the normal group were relatively flat; at more than 250 Hz the contours began an abrupt ascent. The VST values had a logarithmic rising tendency with the increasing age of subjects. In the equal VST contours the frequency of the most sensitive threshold value was 125 Hz in the normal group and 8 Hz in the HAVS group. The patients' VST values were higher than that of the healthy persons. The vibrotactilegram showed that the VST values of the patient groups first shifted at high frequencies and VST loss displayed a "V"-type hollow at 125 Hz and 250 Hz. The quantitative test method of VST was a valuable auxiliary detection method for HAVS. The "V"-type hollow of VST was an early clinical manifestation of HAVS. PMID- 7872201 TI - Changes in the distribution of short-term exposure concentration with different averaging times. AB - For 10 workers (16 worker-chemical combinations) exposed to organic solvents, the distributions of 7.5-min time-weighted average (TWA) concentrations, 15-min TWAs, 30-min TWAs, and 60-min TWAs were examined by the Shapiro-Wilk W test and by plotting the TWA values and logarithmic values on probability paper. The hypothesis of normality of 7.5-min TWA and 15-min TWA was rejected for almost all combinations, while the hypothesis of lognormality was rejected only for a few combinations. For 30-min TWAs and 60-min TWAs, the hypothesis of normality was rejected for five and two combinations, respectively, while the hypothesis of lognormality could not be rejected for any of the combinations. The probability plot also showed that TWA values with averaging times of 7.5 to 60 min were approximately distributed in a lognormal manner. Consequently, there was no evidence against using the lognormal distribution to describe the short-term exposure distribution. Results suggest that statistical methods proposed for evaluating exposure conditions based on lognormal distribution can be useful regardless of averaging time. The appropriateness of estimating exposure distribution with different averaging times by Larsen's equations was also examined using 16 combinations. The geometric mean and geometric standard deviation estimated by Larsen's equations were nearly equal to those estimated by the traditional equations' average, but the difference of the two estimates in each case tended to be large when the ratio of the new averaging time to the original one was large. PMID- 7872202 TI - Occupational exposure and indoor air quality monitoring in a composting facility. AB - The objective of this study was to investigate indoor air quality in a completely covered enclosure used for the aerobic composting of organic wastes originating from vegetable, fruit, and garden refuse. Samples of gases and vapors were taken in the ventilation exhaust ducts. Volatile organic compounds (VOCs) were collected on Tenax absorbent; after thermal desorption they were analyzed by gas chromatography/mass spectrometry. Hydrogen sulfide was determined using Drager test tubes. Microbial samplings were conducted on four sites inside the hall. Microbes were collected using a modified Anderson high-volume sampler, consisting of two impactor stages. Results indicate that the concentrations of VOCs were rather low; only the limonene level was elevated, but it was still well below the current Dutch provisional threshold limit value. Hydrogen sulfide levels found were also far less than the Dutch threshold limit value. Both total bacteria and gram-negative bacterial counts exceeded the provisional Dutch guideline of 10,000 cfu/m3 for indoor air in the work environment. Furthermore, the number of fungi, for the larger part consisting of the genera Aspergillus and Penicillium, which are known to cause respiratory tract disorders, approached the hazardous exposure level. PMID- 7872203 TI - A review of blood lead results from the Third National Health and Nutrition Examination Survey (NHANES III). PMID- 7872204 TI - A simple method for vapor dosing of charcoal sorbent tubes. AB - A method for vapor-dosing of charcoal sorbent tubes (CST) that does not require the expense and effort of a test chamber was used to test the desorption efficiency (DE) of seven solvent vapors, representing six classes of solvents as follows: aromatic hydrocarbons (m-xylene); ether/alcohol (2-ethoxyethanol); vinyl monomers (styrene monomer, vinyl acetate); aliphatic hydrocarbons (n-hexane); aliphatic esters (n-butyl acetate); and aliphatic acrylic monomers (methyl methacrylate). The quantities of the solvents used in these experiments would represent eight-hour exposures to concentrations of approximately 0.2 to 10 ppm. The vapor-dosing experimental system consisted of a loaded filter cassette connected directly to a CST. Vapor was generated by injecting liquid solvent onto the glass fiber filter and drawing air through the system. The solvent was desorbed from the filter and charcoal for analysis. Vapor desorption efficiency was determined from the fraction of the injected solvent evaporated from the filter and the amount recovered from the charcoal. The measured DEs were similar to those reported for liquid dosed charcoal. Vapor dosing of sorbent tubes is more representative of samples collected for industrial hygiene exposure assessment. The system is simple to use and applicable for vapor dosing of any sorbent tube. PMID- 7872205 TI - Acute inhalation toxicology of oxalyl chloride. AB - The acute inhalation LC50 of oxalyl chloride was determined in rats following a one-hour exposure. Four groups of 10 animals per group were exposed to a concentration range of 462-2233 ppm. One set of six animals was exposed to a concentration of oxalyl chloride of 1232 ppm for one hour to evaluate the histopathological change to the lungs. The LC50 is 1840 ppm with the 95% confidence interval between 1531 ppm and 2210 ppm. Microscopically, the lungs from the treated animals exhibited acute bronchiolitis, exudate within the alveoli, and congestion. Pulmonary edema appears to contribute significantly to mortality produced by oxalyl chloride. A comparison of the acute one-hour LC50 of oxalyl chloride to that of hydrogen chloride, phosgene, phosphorus oxychloride, boron trichloride, and chlorine indicates that it shares a comparable degree of acute toxicity to hydrogen chloride and is significantly less toxic via inhalation than the latter four chemicals. PMID- 7872206 TI - Aluminum in parenteral solutions revisited--again. AB - It has been a dozen years since aluminum was first shown to contaminate parenteral nutrition solutions and to be a contributing factor in the pathogenesis of metabolic bone disease in parenteral nutrition patients as well as in uremic patients. However, there are no regulations in place to effectively reduce aluminum contamination of various parenterally administered nutrients, drugs, and biologic products. The purpose of this review is fourfold: 1) to summarize our knowledge of the adverse effects of aluminum on bone formation and mineralization in parenteral nutrition patients; 2) to discuss the possible role of aluminum in the osteopenic bone disease of preterm infants; 3) to show how lack of regulations covering aluminum content of parenteral solutions can lead to vulnerability of new groups of patients to aluminum toxicity, the example being given here is that of burn patients; and 4) to trace the development of efforts at regulating the aluminum contamination of large- and small-volume parenteral drug products and to point out what still needs to be done in this regard. PMID- 7872207 TI - Systematic organization of body-composition methodology: an overview with emphasis on component-based methods. AB - The field of body-composition research currently lacks a systematic organization of methods used to quantitate components at the atomic, molecular, cellular, tissue-system, and whole-body levels of body composition. In this report we propose a classification system for body-composition methodology that proceeds in steps, beginning with division of methods into in vitro and in vivo categories, advances to organization by measurable quantity (property, component, or combined), and ends with grouping of methods by mathematical function (types I and II). Important characteristics of component-based methods are then developed, including a classification of component relationship types, the role of ratios and proportions in type II component-based methods, and the basis of simultaneous equations in multicomponent methods. This classification system, the first founded on a conceptual basis, explains similarities and differences between the many diverse methods, provides a framework for teaching body-composition methodology theories to students, and suggests future research opportunities. PMID- 7872208 TI - Resting metabolic rate and work efficiency of rural Beninese women: a 2-y longitudinal study. AB - This study was performed on 34 female farmers in northern Benin during 2 consecutive years. Body composition, energy intake, energy expenditure, resting metabolic rate (RMR), and energy cost of cycling on a bicycle were measured in three periods per year. Energy intake showed seasonal fluctuations of approximately 1.7 MJ/d in 1990 and 0.6 MJ/d in 1991. Body weight fluctuated between periods, with the lowest weight in preharvest periods. Observed changes in body weight were 2.6 +/- 2.3 and 0.9 +/- 1.7 kg in 1990 and 1991, respectively. The same pattern was observed in both fat mass and fat-free mass. RMR, energy cost of cycling, and delta work efficiency did not show any seasonal changes. It is concluded that metabolic adaptation, as a response to a seasonal food shortage up to 15% of average daily intake, will not occur. PMID- 7872209 TI - Interaction of acute changes in exercise energy expenditure and energy intake on resting metabolic rate. AB - The effects on resting metabolic rate (RMR) of energy intake and exercise energy expenditure were examined in eight trained men under four conditions: 1) high energy flux (HF), 90 min of exercise at 75% VO2max on 3 d while in energy balance; 2) low energy flux (LF), no exercise for 3 d while in energy balance; 3) negative energy balance (NEB), exercise on 3 d while consuming low-flux meals; and 4) positive energy balance (PEB), no exercise for 2 d while consuming high flux meals. Eight untrained men were studied in LF. There were effects of exercise energy expenditure and energy intake on RMR, and an exercise x diet interaction (P < 0.05). RMR was greater in trained than in untrained subjects only when trained subjects were in HF. These data indicate that RMR is influenced by exercise, energy intake, and their interaction and suggest that higher RMR in trained vs untrained individuals results from acute effects of HF rather than from a chronic adaptation to exercise training. PMID- 7872210 TI - Mathematical ratios lead to spurious conclusions regarding age- and sex-related differences in resting metabolic rate. AB - Resting metabolic rate (RMR) data have been normalized by dividing RMR by fat free mass (FFM) (ie, ratio method), or by using a regression-based approach. We compared both data-normalization procedures on age- and sex-related differences in RMR. The ratio method showed no differences in adjusted RMR between older men (0.084 +/- 0.004 kJ.FFM-1.min-1) and younger men (0.082 +/- 0.003 kJ.FFM-1.min 1), whereas analysis of covariance showed a lower (P < 0.01) adjusted RMR in older men (4.81 +/- 0.04 kJ/min) than in younger men (5.14 +/- 0.04 kJ/min). In another example, the ratio method showed that women had a higher (P < 0.05) adjusted RMR (0.10 +/- 0.004 kJ/min) than did men (0.08 +/- 0.003 kJ/min), whereas analysis of covariance showed a lower (P < 0.01) adjusted RMR in women (4.45 +/- 0.03 kJ/min) than in men (4.62 +/- 0.03 kJ/min). The ratio method provides misleading conclusions regarding sex- and age-related differences in RMR when compared with a regression-based approach. PMID- 7872211 TI - Effects of aerobic exercise and dietary carbohydrate on energy expenditure and body composition during weight reduction in obese women. AB - To test the benefits of aerobic exercise and dietary carbohydrate during reduced energy feeding, 23 obese women (44 +/- 4% fat) were randomly assigned to either aerobic exercise (Ex) or no exercise (Nx), and to a low-fat (LF) or low carbohydrate (LC) reducing diet (5.00 +/- 0.56 MJ/d) for 12 wk. Changes in body composition, postabsorptive resting metabolic rate (RMR), thermic effect of a meal (TEM), and total daily energy expenditure (TDEE) were measured by respiratory gas exchange and doubly labeled water. Significant effects of Ex included a greater loss of fat mass (Ex: -8.8 +/- 2.1 vs Nx: -6.1 +/- 2.3 kg, P = 0.008) and maintenance of TDEE (Ex: +0.07 +/- 1.23 vs Nx: -1.46 +/- 1.04 MJ/d, P = 0.004), due to a difference in physical activity (Ex: +0.75 +/- 1.06 vs Nx: 0.61 +/- 1.03 MJ/d, P = 0.006), which was not attributable solely to the Ex sessions. RMR in both groups decreased comparably (-0.54 MJ/d), and TEM (% of meal) did not change. Diet composition did not significantly influence body composition or energy expenditure changes, but a greater weight loss was observed after the LC than after the LF (-10.6 +/- 2.0 vs -8.1 +/- 3.0 kg, P = 0.037) diet. The addition of aerobic exercise to a low-energy diet was beneficial in the treatment of moderate obesity because of its favorable effects on body composition, physical activity, and TDEE. PMID- 7872212 TI - Undernutrition among Bedouin Arab children: a follow-up of the Bedouin Infant Feeding Study. AB - After 10 y of urban settlement, 680 Bedouin Arab children, who had had anthropometric assessment from birth (1981-1982) through early childhood, were reassessed in 1991-1992 to compare the rates of stunting in early and later childhood as well as to describe the factors influencing current height-for-age. Stunting had dropped from 32.7% at 18 mo to 7.2% at 10 y in the 1981 birth cohort and dropped from 17.5% at 9 mo to 8.2% at 9 y in the 1982 birth cohort. Based on a multiple-linear-regression analysis, height in early childhood and maternal height were statistically significantly and positively associated with current mean height-for-age in both cohorts. In the 1982 cohort socioeconomic status in early childhood was positively and current family size was negatively and significantly associated with current mean height-for-age. Thus, conditions that were present in early childhood had the largest influence on current height. In 1992, 10% and 6% of the infant siblings of the 1981 and 1982 cohorts, respectively, were stunted compared with 17% and 1% of the siblings aged 1-2 y of the respective cohorts. Therefore, the high rates of early childhood stunting in 1981-1982 appeared to be a birth cohort-specific phenomenon. PMID- 7872213 TI - Changes in energy expenditure, anthropometry, and energy intake during the course of pregnancy and lactation in well-nourished Indian women. AB - Basal metabolic rate (BMR), thermic effect of a meal (TEM), anthropometry, and dietary intakes were measured in 18 control subjects; 18 pregnant women at 12, 24, and 34 wk gestation; and in 17 of these women at 12 and 24 wk postpartum, to uncover any metabolic economy associated with either pregnancy or lactation. Results indicated that the BMR and TEM were not associated with any energy saving either during pregnancy or lactation. Mean weight gain from 12 wk gestation to term was 11.4 +/- 3.7 kg; mean birth weight of the infants was 3.06 +/- 0.41 kg. Estimated gain in adipose tissue and fat mass were 3.1 +/- 3.6 and 2.5 +/- 2.9 kg, respectively. Energy cost of pregnancy was estimated to be 303 +/- 171 MJ. The cumulative increase in energy intake over the last two trimesters of pregnancy was 290 +/- 280 MJ, meeting a large part of the total estimated cost of pregnancy. Weight gained by infants who were exclusively breast-fed from birth to 12 wk of age was used as a proxy indicator of adequate lactational performance. The extra energy required during lactation appeared to have been met largely by increases in energy intake, rather than by any metabolic economy or increase in fat mobilization. PMID- 7872214 TI - Calcium homeostasis and bone metabolism during pregnancy, lactation, and postweaning: a longitudinal study. AB - Ten women were followed serially to determine the effect of stages of reproduction on calcium and bone metabolism. The study periods were nonpregnant nonlactating, the end of each trimester of gestation, 3 mo lactation, and postweaning. Comparisons were with nonpregnant nonlactating status for each individual. Fractional calcium absorption (P < 0.0001) and concentrations of 1,25 dihydroxyvitamin D (P < 0.01) were higher in the second and third trimesters. Total urinary calcium was higher during pregnancy and lower postweaning. Parathyroid hormone (PTH) concentrations were higher only postweaning (P < 0.01). Markers of bone turnover increased at the third trimester and during lactation: serum tartrate resistant acid phosphatase and bone specific alkaline phosphatase, and urinary deoxypyridinoline (P < 0.01). Serum procollagen I carboxypeptides increased only in the third trimester (P < 0.01). Bone mineral density by single photon absorptiometry did not differ by period. We conclude that absorption and urinary excretion of calcium increase during pregnancy whereas bone turnover increases during late pregnancy and lactation; only renal changes consistent with an increase in PTH were seen postweaning. PMID- 7872215 TI - Activities of trypsin and lipase in duodenal aspirates of preterm infants: influence of dietary protein and fat composition. AB - The influence of three different feeding regimens on the activities of pancreatic lipase and trypsin in duodenal aspirates and on fecal nitrogen and fat excretion was studied in 35 healthy preterm infants after a 2-wk feeding period. Eleven infants received a standard preterm formula (without long-chain polyunsaturated fatty acids), 12 were fed with an experimental formula that only differed from the standard formula in fat blend composition (with long-chain polyunsaturated fatty acids), and 12 infants received human milk fortified with protein and energy to have similar nitrogen and energy contents as the two formulas. There were no significant differences in duodenal trypsin activities among the groups. In the group fed the standard formula, lipase activity was significantly lower than in the group fed the experimental formula (standard formula group: 8.4 +/- 3.5 kU/L; experimental formula group: 13.8 +/- 4.8 kU/L; P < 0.05) but there was no significant difference between the experimental formula group and the human milk group (15.1 +/- 4.2 kU/L). Fecal nitrogen as well as fat excretion were similar in the three feeding groups. The data suggest that dietary fat composition can influence the postnatal development of duodenal lipase activity in preterm infants. PMID- 7872216 TI - Maternal anthropometric status and lactation performance in a low-income Honduran population: evidence for the role of infants. AB - As part of a study on the optimal timing of complementary feeding in Honduras, we assessed breast milk volume and composition at 4, 5, and 6 mo in 141 low-income women who were randomly assigned to exclusively breast-feed for the first 6 mo or to complement breast milk with prepared solid foods beginning at 4 mo. Milk volume averaged 797 +/- 139 g/d at 4 mo. Maternal body mass index was positively associated with infant birth weight and milk energy density. In multivariate analyses in which group assignment was controlled for, milk volume was positively associated with birth weight but negatively associated with milk energy density. Infant breast milk energy intake was positively associated with birth weight and milk energy density. Maternal anthropometric status was not a significant predictor of milk volume or infant energy intake when birth weight and milk energy density were included in the models. These results indicate that infant characteristics, such as birth weight and the ability to self-regulate intake in response to milk energy density, mediate the relationship between maternal anthropometric status and lactation performance. PMID- 7872217 TI - Relative effects on serum lipids and apolipoproteins of a caprenin-rich diet compared with diets rich in palm oil/palm-kernel oil or butter. AB - Two randomized, blind studies measured changes in serum cholesterol, other serum lipids, and apolipoprotein (apo) concentrations in hypercholesterolemic men consuming caprenin (Cap)-rich diets after either baseline diets enriched in palm oil/palm-kernel oil (PO/PKO) or butter. The triglyceride Cap contains 45% 22:0 and 50% 8:0-10:0. Compared with baseline values established at 3 wk on the PO/PKO diet, the 17 subjects on the Cap diet showed significant reductions after 6 wk in HDL cholesterol (HDL-C), HDL2-C, and HDL3-C and a significant increase in the ratio of total cholesterol, LDL-C, triglycerides, apo B-100, or apo A-I were seen. Compared with baseline values established at 3 wk on the butter diet, after 6 wk the seven subjects receiving the Cap diet showed no significant changes in the lipid and apolipoprotein indexes analyzed. These data show that one or more of 8:0, 10:0, and 22:0 fatty acids can contribute to hypercholesterolemia in men. PMID- 7872218 TI - Diet and body composition as determinants of basal lipolysis in humans. AB - Determinants of basal lipolysis were investigated in a group of 23 volunteers of both sexes. Body composition was measured by underwater weighing and resting metabolic rate with indirect calorimetry. Insulin sensitivity was determined by using the minimal model of Bergman. The rate of appearance of palmitic acid in the blood was measured with 14C-1-palmitate as the tracer administered as a nonprimed constant infusion. Simple and stepwise-regression analyses were performed to determine correlations and to generate a multivariate model to examine the determinants of basal lipolysis. Fat intake (as a percent of total energy intake) was correlated with basal lipolysis (r = 0.57, P < 0.005) as well as protein intake (as a percent of energy intake) (r = -0.46, P = 0.03) in univariate analysis. Body weight (r = 0.56, P = 0.005) explained a greater portion of the variance in lipolysis than fat-free mass (r = 0.44, P < 0.05) or fat mass (NS). Independent predictors of basal lipolysis were determined by stepwise regression. The best model generated included fat intake, fat-free mass, carbohydrate intake, and daily energy intake as significant determinants of lipolysis (r = 0.89, P < 0.001). The insulin sensitivity index and sex were not independent predictors of basal lipolysis. Thus, our data support either body weight or fat-free mass as more appropriate indexes than fat mass to normalize basal rates of lipolysis in humans. Furthermore, the macronutrient composition of the diet is an important determinant of lipolysis and thus should be considered in future experimental designs. PMID- 7872219 TI - Consumption of red wine with meals reduces the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation. AB - The effect of consumption of red or white wine (11% alcohol) with meals on the propensity of plasma and low-density lipoprotein (LDL) to undergo lipid peroxidation was studied in 17 healthy men who were divided into two groups: 8 received 400 mL red wine/d for 2 wk, and 9 received a similar amount of white wine. Red wine consumption for 2 wk resulted in a 20% reduction in the propensity of plasma to undergo lipid peroxidation (in the presence of a free-radical generating system) as determined by the thiobarbituric acid reactive substances (TBARS) assay. In parallel, red wine consumption reduced the propensity of the volunteers' LDL to undergo lipid peroxidation (in response to copper ions) as determined by a 46%, 72%, and 54% decrease in the content of TBARS, lipid peroxides, and conjugated dienes in LDL, respectively, as well as by a substantial prolongation of the lag phase required for the initiation of LDL oxidation. On the contrary, dietary consumption of white wine for 2 wk resulted in a 34% increase in plasma's propensity to undergo lipid peroxidation and also in a 41% increased propensity of the LDL to undergo lipid peroxidation. The antioxidant effect of dietary red wine on plasma lipid peroxidation was not secondary to changes in the plasma vitamin E or beta-carotene content but could be related to the elevation of polyphenol concentration in plasma and LDL. Thus, some phenolic substances that exist in red wine, but not in white wine, are absorbed, bind to plasma LDL, and may be responsible for the antioxidant properties of red wine. PMID- 7872220 TI - Phenylalanine and tyrosine kinetics in young men throughout a continuous 24-h period, at a low phenylalanine intake. AB - We determined the daily rates of whole-body phenylalanine oxidation (phe-Ox) and hydroxylation (phe-OH) in young men receiving [1-13C]phenylalanine and [2H2]tyrosine via primed, constant intravenous (n = 5) or oral (n = 7) infusions for a consecutive 24 h (12-h fast followed by 12-h fed period), and given a low phenylalanine (21.9 mg.kg-1.d-1), no-tyrosine, but otherwise adequate L-amino acid-based diet for 6 d before the tracer study. Estimates of the daily rates of phe-Ox and phe-OH were significantly higher (P < 0.001) for the subjects receiving the oral tracer, with estimates of phe-Ox obtained with the oral tracer during the 12-h fast period being close to those predicted from similar 24-h leucine kinetic studies (Am J Clin Nutr 1994;59:1000-11). There was generally poor agreement between the measured 24-h rates of phe-Ox and phe-OH compared with the daily rates as predicted from the last hour of the 12-h fast and 5th hour of feeding. From the 24-h data, daily phenylalanine balances were estimated to be positive with the intravenous-tracer protocol and negative with the oral-tracer group. Our results question the adequacy of current international recommendations for aromatic amino acid requirements in healthy adults. PMID- 7872222 TI - Differences in calcium metabolism between adolescent and adult females. AB - A 3-wk metabolic study measured calcium balance in 14 white adolescent girls and 11 young adult women. Subjects were housed in a sorority to simulate a free living environment. A 6-d menu cycle consisted of foods typically eaten by teenagers and averaged 1332 mg Ca/d. Adolescents had a significantly higher calcium balance of 326 +/- 107 mg/d (mean +/- SD) than adults, who averaged 73 +/ 104 mg/d (P < 0.001). No adult > age 21 y was in positive calcium balance. Adolescents had lower urinary calcium excretion values (P < 0.001), lower fecal calcium excretion (P < 0.01), and greater net absorption (P < 0.001) than adults. Calcium balance was negatively correlated with years postmenarche (r = -0.788, P = 0.0001) and height (r = -0.650, P = 0.001). Net calcium absorption was positively correlated with parathyroid hormone concentrations (r = 0.537, P = < 0.01). Thus, the growth demands of adolescents are met by more efficient net absorption and retention of calcium compared with young adults. PMID- 7872221 TI - Pyridoxine supplementation protects mice from suppression of contact hypersensitivity induced by 2-acetyl-4-tetrahydroxybutylimidazole (THI), ultraviolet B radiation (280-320 nm), or cis-urocanic acid. AB - Evidence exists implicating the epidermal ultraviolet B (UVB) photoproduct cis urocanic acid as an immunogenic mediator of the systemic suppression of T cell mediated immunity by UVB exposure. Cis-urocanic acid appears to act via histamine receptor pathways, and histamine receptor antagonists and other imidazole ring compounds may modify its immune suppressing action. A component of the food coloring substance ammonia caramel, 2-acetyl-4-tetrahydroxybutylimidazole (THI), which is known to cause lymphopenia in rats, appears to suppress immunity by a similar pathway when the contact hypersensitivity reaction has been the immune function assay in mice. The induction of lymphopenia in rats by THI is inhibited by the vitamin pyridoxine. This study demonstrates that the suppression of contact hypersensitivity in mice by UVB radiation, cis-urocanic acid, or THI is strongly inhibited by supplemental pyridoxine, fed at 30 mg/kg diet, in comparison with the normal diet, which supplies 7 mg pyridoxine/kg diet. These results suggest that pyridoxine competes with cis-urocanic acid and THI for the same binding site or receptor, which we postulate to be a histamine-like T lymphocyte receptor, and that a role may exist for the control of photoimmunosuppression by this vitamin. PMID- 7872223 TI - Resting energy expenditure in patients with thalassemia major. AB - The effect of non-iron-deficiency anemia was studied in seven patients with thalassemia major (beta thalassemia) ages 22-30 y. Each patient was studied before and 3 days after blood transfusion. Hemoglobin concentrations increased significantly after blood transfusion (111-153 vs 81-102 g/L, P < 0.02). Heart rate decreased from 96 +/- 12 to 81 +/- 7 beats/min (mean +/- SD; P < 0.05). No significant difference was found in venous blood pH, bicarbonate concentrations, or lactic acid concentrations before and after blood transfusion. Resting energy expenditure (REE) was greater before blood transfusion in absolute numbers and as a percentage of the predicted value, and returned to normal range thereafter (6138 +/- 112 vs 5678 +/- 738 kJ.kg-1.d-1 and 111.7 +/- 11.3% vs 103.2 +/- 7.8%, respectively). Protein contribution to REE was low before blood transfusion (9.7 +/- 4.2%) and returned to normal range thereafter (15.3 +/- 5.2%) (P < 0.09). This finding may indicate that increased protein turnover as well as increased cardiac work contribute to the observed increase in REE. PMID- 7872224 TI - Effect of short-term ingestion of konjac glucomannan on serum cholesterol in healthy men. AB - The effects of the soluble fiber konjac glucomannan (GM) on serum cholesterol concentrations were investigated in 63 healthy men in a double-blind crossover, placebo-controlled study. After a 2-wk baseline period, the subjects were given 3.9 g GM or placebo daily for 4 wk. After a washout period of 2 wk, crossover took place, followed by another 4 wk of treatment. The subjects were encouraged not to change their ordinary diets or general lifestyle during the investigation. GM fibers reduced total cholesterol (TC) concentrations by 10% (P < 0.0001), low density-lipoprotein cholesterol (LDL-C) concentrations by 7.2% (P < 0.007), triglycerides by 23% (P < 0.03), and systolic blood pressure by 2.5% (P < 0.02). High-density-lipoprotein cholesterol (HDL-C) and the ratio of LDL-C to HDL-C did not change significantly. No change in diastolic blood pressure or body weight was observed. No adverse effects were observed. The results of this study show that GM is an effective cholesterol-lowering dietary adjunct. PMID- 7872225 TI - Iron deficiency and anemia of chronic disease in elderly women: a discriminant analysis approach for differentiation. AB - To differentiate iron-deficiency anemia and anemia associated with chronic inflammatory diseases in elderly women, subsets of laboratory, dietary, and functional assessment variables were obtained by using discriminant analysis. Fifty-one subjects (70-79 y of age) were classified into one of four groups on the basis of the presence of iron deficiency and chronic inflammatory disease. Iron deficiency was defined on the basis of a significant response in hemoglobin concentration after iron supplementation. The discriminating subset of laboratory tests consisted of measures for serum ferritin, plasma transferrin receptors, and erythrocyte sedimentation rate. The discriminant function classified subjects into iron-deficient, anemia of chronic disease, or a category in which the two coexist, with an error rate of 18.6%. The addition of other variables (dietary iron and functional assessment information) did not appreciably improve the classification. The results of these three key laboratory tests may help to identify functional iron deficiency in the presence of chronic inflammation. PMID- 7872226 TI - Influence of nutrition, thyroid hormones, and rectal temperature on in-hospital mortality of elderly patients with acute illness. AB - The present study was undertaken to investigate the interrelation of nutrition, core temperature, and thyroid function and their influence on survival of patients aged > or = 70 y admitted to the hospital with acute conditions. Sixty seven patients entered the study. Nutritional state, thyroid function, rectal temperature, and the APACHE II score were recorded at admission. The patients were followed until death or hospital discharge. Patients with a serum albumin concentration < 35 g/L showed a lower triiodothyronine (T3) concentration, a higher reverse triiodothyronine (rT3) concentration, and a higher death rate. Prior weight loss (> or = 10%) did not influence thyroid status but increased the mortality rate. Eleven patients were hypothermic (< 36.5 degrees C) and had a higher mortality, lower total T3 concentration, and higher rT3 concentration than the normothermic or hyperthermic subjects. Serum albumin, body weight, and total T3 concentration were higher in survivors (n = 51) than in nonsurvivors (n = 16). Ongoing weight loss and hypoalbuminemia at admission are highly prevalent in elderly people with acute disease, and influence their clinical outcome. Mild hypothermia was a good predictor of death. Hypoalbuminemia and hypothermia were associated with low T3 and high rT3 values. PMID- 7872227 TI - Reduction of hyperlipidemia and proteinuria without growth retardation in nephritic rats by a methionine-supplemented, low-soy-protein diet. AB - Effect of a low-soy-protein-isolate (SPI) diet supplemented with methionine on hyperlipidemia, proteinuria, and hypoalbuminemia was studied in rats with nephrotoxic serum nephritis (NSN). Rats were fed experimental diets for 14 d after an injection of nephrotoxic serum. An 8.5%-SPI diet (8.5S), as compared with a basal 20%-SPI diet (20S), improved the hyperlipidemia, proteinura, and hypoalbuminemia secondary to NSN but retarded the growth of rats. The addition of 0.3% methionine to 8.5S (8.5SM) alleviated the growth retardation without loss of the above-mentioned beneficial effects. 8.5SM was found to suppress hepatic cholesterol synthesis compared with 20S. These results suggest that the methionine-supplemented low-SPI diet has a beneficial effect on hyperlipidemia, proteinuria, and hypoalbuminemia without inducing either growth retardation or severe fatty liver in nephritis. They also suggest that the hypocholesterolemic effect of 8.5SM in nephritic rats may be partly attributable to reduced hepatic cholesterol synthesis. PMID- 7872229 TI - Periconceptional folate and neural tube defects. PMID- 7872228 TI - Prolonged inhibition of platelet aggregation after n-3 fatty acid ethyl ester ingestion by healthy volunteers. AB - This study addressed two questions: 1) whether a relatively low dose of n-3 fatty acid ethyl esters (n-3 FAs) administered to healthy volunteers for a prolonged period of time would exert beneficial effects on plasma lipids, platelet function, and thromboxane biosynthesis; and 2) whether a short-term loading treatment (6 wk) with 6 g n-3 FAs/d followed by 12 wk with 3 g/d results in more pronounced effects. After 6 wk treatment a reduction of plasma triglyceride concentration and an accumulation of EPA and DHA in plasma were observed. A longer period of treatment with n-3 FAs was necessary to affect platelet aggregation and thromboxane A2 biosynthesis. At 12 and 18 wk, platelet aggregation, thromboxane A2 formation, and the excretion of thromboxane metabolites in urine were reduced, particularly in subjects who received 6 g n-3 FAs/d during the initial 6 wk. After treatment ended, triglyceride and thromboxane A2 biosynthesis returned to baseline values within 4 wk, whereas platelet aggregation remained impaired for > or = 14 wk. The longlasting impairment in platelet aggregation was accompanied by the retention of n-3 FAs in platelet phospholipids. PMID- 7872230 TI - The merits of race-specific standards. PMID- 7872231 TI - Dietary trans fatty acids and lipoprotein cholesterol. PMID- 7872232 TI - Experimental evidence of a plant meridian system: III. The sound characteristics of phylodendron (Alocasia) and effects of acupuncture on those properties. AB - Studies on the sound characteristics of phylodendron performed by measuring the power of plant leaves with a laser beam found that the leaves of phylodendron could produce sound waves at relatively low frequencies (from 50 Hz to 120 Hz). Furthermore, it was found that those leaves could accept external sound wave stimulations, with frequencies lower than 150 Hz giving the strongest responses. When the plants were under stress, such as drought, the sound emissions from the plant's leaves increased approximately 20-30 dB, while the range of response to external sound wave stimulation decreased 10-20 dB. However, these increased emissions returned to normal six minutes after watering. When the stainless steel needles were inserted into the petiole of the plant, spontaneous sound production was increased about 40 dB for the main vein and 6 dB for the mesophyll. This is our third report on experimental evidence that plants might have a meridian system as in humans and other animals. PMID- 7872233 TI - Effects of acupuncture on blood pressure and plasma renin activity in two-kidney one clip Goldblatt hypertensive rats. AB - Shih-Hsuan [Sipseon (EX-UE-11)] are Curious loci lying outside of the meridians on the tips of each finger. These loci have long been the acupuncture sites for the treatment of cardiovascular disease in oriental medicine. Alterations in the renin-angiotensin system have been considered as the pathophysiological basis of the origin and/or maintenance of hypertension. Activation of the plasma or tissue renin-angiotensin system may be one of the cause of hypertension. The aim of the present study was to elucidate the effects of acupuncture on blood pressure and plasma renin activity. Acupuncture was applied on the EX-UE-11 of two-kidney one clip Goldblatt hypertensive rats. Both the systolic blood pressure and the plasma renin activity decreased significantly after treatment with acupuncture on the EX UE-11. In the sham-operated and control rats, the procedure influenced the parameters without significant changes. The results suggest that the suppressive hemodynamic effect of acupuncture on the EX-UE-11 may be related to changes in plasma renin activity. PMID- 7872235 TI - Qigong therapy--its effectiveness and regulation. AB - Qigong has become increasingly popular as a modality in traditional Chinese medical care. It may be effective in treating diseases. However, it is not uncommon to hear complaints about the ineffectiveness of such treatment. This paper attempts to look at the recent promotion of Qigong as an effective form of health care and the regulation of Qigong practitioners in China by a review of literature and interviews with key informants. Although it is premature to conclude that Qigong is another therapeutic modality in traditional Chinese medicine, it is also premature to rule out the possible therapeutic efficacy of Qigong, in particular, internal Qi. Even if medical Qigong is effective, the establishment and enforcement of standards of practice and codes of ethics amongst Qigong masters will remain unresolved as there has not yet been any effective way to assess the competence of a Qigong master. Although a number of control measures have been proposed in this paper, a better understanding of the educational, professional and ethical standards and efficacy of such a practice is required. PMID- 7872234 TI - Gentle and strong acupuncture: a short review of the two main approaches to treatment. AB - For centuries, the Qi secondary pathways have been known. Although in many diseases puncturing their points can be very effective, such treatment, surprisingly, is used very restrictively. In this article we present some methods allowing the relief of these pathways in their most limited sites. Such approaches are referred to as gentle acupuncture which intends to clear energy channels. In addition, methods of working with principal channels using the Five Element-Phase points are presented. These methods, considering energy imbalance at a level of the whole organism, are called strong acupuncture because of their strong influence on the Energy of the body. PMID- 7872236 TI - Hepatoprotective effects of Taiwan folk medicine: Ixeris chinensis (Thunb.) Nak. on experimental liver injuries. AB - The hepatoprotective effects of Ixeris chinensis (Thunb.) Nak. were studied on acute hepatitis induced in mice by a single dose of carbon tetrachloride (31.25 microliters/kg, ip) or acetaminophen (600 mg/kg, ip), and in rats by a single dose of beta-D-galactosamine (188 mg/kg, ip). Hepatoprotective activity was monitored by estimating the serum transaminases (SGOT and SGPT) levels and histopathological changes in the livers of experimental animals. The Ixeris chinensis (Thunb.) Nak. extracts significantly inhibited the acute elevation of serum transaminases. Histopathologically, the crude I. chinensis extract significantly ameliorated hepatotoxin-induced histopathological changes in the livers of experimental animals. All pharmacological and histopathological effects of Ixeris chinensis (Thunb.) Nak. were compared with Bupleurum chinense DC., which has been previously reported as a treatment herb for hepatitis. PMID- 7872237 TI - Effect of shi-ka-ron and Chinese herbs on cytokine production of macrophage in immunocompromised mice. AB - Shi-Ka-Ron is a prescription composed of 8 crude extracts of Chinese herbs. It reduces suppression of cytokine production by peritoneal macrophages in mice Immunocompromised by the anti-tumor agent, cyclophosphamide (CY), in vivo. Although it dose not increase IL-1 production in vitro, it enhances TNF production. We found that Ginseng radix, Lithospermi radix, Astragli radix and Glycyrrhizae radix somewhat reduced suppression of cytokine production in CY treated macrophages. Especially, Glycyrrhizae radix shows an active immune response both in vivo and in vitro. Our results suggested that the mechanism underlying immunomodulation of Shi-Ka-Ron is closely related to cytokine production: each herb stimulating macrophages. PMID- 7872238 TI - Suppression by kampo medicine, sho-saiko-to, on papillomas induced by 7,12 dimethylbenz(a)anthracene in mice. AB - Sho-saiko-to (SST) is a Japanese modified, traditional Chinese herbal medicine (Kampo medicine) consisting of seven medical plants. We examined the effects of SST on formation and growth of squamous cell papillomas induced by 7,12 dimethylbenz(a)anthracene application in mouse skin. Chronic oral administration of SST reduced the incidence and growth of papillomas with the reduction of activities of succinate-dehydrogenase and thymidylate synthetase, which were evaluated as the cell viability and DNA synthesis via the de novo pathway, respectively. PMID- 7872239 TI - Improved isolated heart contractility and mitochondrial oxidation after chronic treatment with Panax ginseng in rats. AB - Heart mitochondria freshly isolated from ginseng treated rats respired higher at ADP-induced, state 3 respiratory rates and with greater respiratory indices. These mitochondria were less susceptible to experimentally-induced functional impairment. Control heart mitochondria incubated with ginseng extract also showed that ginseng prevented mitochondria from incubation induced deterioration with NAD-linked substrates. Comparison of force of contraction of isolated, perfused and electrically paced hearts showed that deterioration of the force of heart contraction was consistently smaller throughout the experiment in hearts from ginseng treated rats. These results indicated that Panax ginseng was able to delay experimentally induced heart mitochondrial impairment and muscle contraction deterioration. PMID- 7872240 TI - Effect of flavan-3-ol tannins purified from Camellia sinensis on lipid peroxidation of rat heart mitochondria. AB - We induced lipid peroxidation in rat heart mitochondria with FeSO4 and compared the inhibitory effect of various flavan-3-ol tannins on it. These tannins were purified from Chinese tea (Camellia sinensis). Oxygen consumption and malondialdehyde formation were used to quantitate the amount of lipid peroxidation. The free radical scavenger activity of tannins was then measured with a diphenyl-p-picrylhydrazyl method. These tannins significantly inhibited lipid peroxidation at micromolar concentration. Their potencies were higher than that of Trolox, a water soluble analogue of vitamin E. Since epicatechin-3-O gallate, epigallocatechin-3-O-gallate and gallocatechin-3-O-gallate were more potent than other flavan-3-ol tannins in these assays, we considered that a galloyl group in 3-O-position increased the scavenger activity of flavan-3-ol tannins as well as their potency in inhibiting lipid peroxidation. PMID- 7872241 TI - The effect of ninjinyoeito on human aorta endothelial cells. AB - We studied the effect of Ninjinyoeito in relation to the endothelial cells of the human aorta. Ninjinyoeito produced a cell proliferation acceleration effect, resulting in suppression of the synthesis and acceleration of the disintegration of endothelin, which acts as a vasoconstrictor and vasopressor. Also, acceleration of the synthesis of prostacyclin, which shows antithrombosis and platelet coagulation suppressing effects, was observed. The results suggest that Ninjinyoeito accelerates physiological function of in vitro human aorta endothelial cells. PMID- 7872242 TI - Effects of hochu-ekki-to, a Japanese kampo medicine, on cultured hamster epididymal cells. AB - In Japan, Hochu-ekki-to (TJ-41), a Japanese Kampo preparation is used extensively in the treatment of idiopathic male infertility. In order to elucidate the mechanism of how this drug affects spermatogenesis, we examined the effects of the sera from male mice to which TJ-41 was administered orally, on protein synthesis in cultured hamster epididymal cells. Golden hamster epididymal cells were cultured in RPMI1640 medium supplemented with FCS for 7 to 10 days. After the initial culture period, the medium was changed to RPMI1640 supplemented with 1 microCi/ml [3H]-leucine and 10% serum from male ICR mice to which TJ-41 was orally administered for 7 days. The culture was then continued for 20 hours, and the uptake of [3H]-leucine into the cultured hamster epididymal cells was measured. The uptake of [3H]-leucine was significantly higher (p < 0.05) in cells cultured in media supplemented with sera from the TJ-41 treated mice than in cells cultured with control sera. Elements in the sera from control and TJ-41 treated mice were analyzed by high performance liquid chromatography (Waters HPLC, type 510; Milipore) with a mu-Bondapack C18 column. Several new peaks were detected in the sera from TJ-41 treated mice. These results and the clinical data suggest that TJ-41 may promote the synthesis of several proteins which might he related to the functional maturation of spermatozoa in the epididymis. PMID- 7872243 TI - Bu ji (hozai) for treatment of postoperative gastric cancer patients. AB - We proposed that postgastrectomy cancer patients with organ deficit were xu zheng, or of deficient constitution, and administered bu ji or supplementary regimen to them. With alleviation of the symptoms, our diagnosis seemed correct from the traditional medicine perspective. Interleukin 2 reactivity, natural killer activity, nutritional index and bone mineral indices also improved. Such results suggest that our diagnosis was also correct according to Western medical theory. In addition, nutrition seemed to have positive relationship with NK activity and bone mineral content. Therefore, administration of bu ji seemed useful to improve the quality of life of postoperative cancer patients. PMID- 7872244 TI - Traditional Chinese medicine typing of affective disorders and treatment. AB - According to the theory of Traditional Chinese Medicine (TCM), 50 patients with affective disorders were typed into the categories of depressed liver resulting in fire, mild Yang deficiency and mild Yin deficiency and were treated with Xiao Yao San Jia Wei. The results are 26 patients with marked improvement, 17 patients with improvement and 7 patients with no improvement. PMID- 7872245 TI - A useful diagnostic method for drug-induced pneumonitis: a case report. AB - A 51 year-old male was admitted to our hospital with chief complaints of fever, dry cough and dyspnea. Chest X-ray films and his history of taking Chinese medicine for liver dysfunction were suggestive of drug-induced pneumonitis. Lymphocyte stimulation test (LST) to causative Chinese medical drugs of Sho-saiko to and Dai-saiko-to was negative with peripheral blood lymphocytes (PBL), but was positive with lymphocytes from bronchoalveolar lavage fluid (BALF). In vivo challenge test for Sho-saiko-to was positive. The LST with BALF-lymphocytes proved to be very useful in making a diagnosis of drug-induced pneumonitis. PMID- 7872246 TI - Radionuclide venography by subcutaneous injection of Tc-99m pertechnetate at acupuncture point K-3: a case report. AB - Recently, we developed a new method of radionuclide venography of lower limbs, namely SC-RNV, by subcutaneous injection of Tc-99m pertechnetate at acupuncture points K-3. In this study, we applied this method to evaluate the venous drainage of lower limbs in a patient with severe varicose veins and edematous swelling of the left lower extremity. For comparison, an ascending radionuclide venography by intravenous injection of Tc-99m MAA (IV-RNV) was also done. The SC-RNV showed normal venous drainage of the right side but complete obstruction of the left popliteal vein with a prominent collateral flow, compatible to the findings of IV RNV. The findings in this case again demonstrated that SC-RNV may be useful as an alternative method of venography as previously suggested. PMID- 7872247 TI - Activated protein C resistance and inherited thrombosis. PMID- 7872248 TI - Cytopathology and surgical pathology. Parallel pathways, same purpose. PMID- 7872249 TI - Oxyphilic papillary thyroid carcinomas. AB - Oxyphilic papillary carcinomas of the thyroid have not been extensively studied because they are rare. The morphology and behavior of 34 cases were described. The average age was 44.1 years, the female-to-male ratio was 3.9:1, and the average diameter of the tumors was 2.3 cm. All had papillary structures present. In 31 cases, there was capsular or parenchymal invasion. Six cancers had local lymph node metastases. The average follow-up for 29 patients was 8.1 years. Tumors reappeared in four patients; one patient died from recurrent disease, one patient with disease died due to an unrelated carcinoma, and two patients were treated successfully. Twenty-seven patients at the end of follow-up were alive with no detectable thyroid cancer. The majority of patients remained free of tumor, especially those younger than 50 years. PMID- 7872250 TI - Monoclonal antibody, Mab 12C3, is a sensitive immunohistochemical marker of early malignant change in epithelial ovarian tumors. AB - A murine monoclonal antibody (MAb 12C3) that is specific to human ovarian carcinomas was generated by immunizing mice with a human ovarian germinoma cell line (JOHYC-2). The antigen distribution that was defined by MAb 12C3 in normal and malignant human tissues was analyzed by immunohistochemistry on paraffin embedded and frozen sections. The antibody reacted with 67.7% (21 of 31 cases) of epithelial ovarian carcinomas (6 of 12 cases of serous cystadenocarcinoma, 5 of 7 cases of mucinous cystadenocarcinoma, 7 of 9 cases of clear cell carcinoma, 3 of 3 cases of endometrioid adenocarcinoma), but did not react with any of the benign epithelial ovarian adenomas tested. Partial regions of borderline ovarian malignancies that exhibited marked papillary projection of the lining cells with cellular atypia reacted positively with MAb 12C3 in 14 of 25 cases (56.0%). The histologic features of regional early malignant change corresponded to the expression of the MAb 12C3 epitope in the borderline malignant tumor cells. There was a low frequency of reaction (4.3%) between the antibody and other gynecologic and nongynecologic malignancies (46 cases of 12 tissues). In normal tissues, the antibody reacted positively with only three tissues, including corpora lutein cells, excretory ducts in the submandibular gland, and basal cells of the sebaceous glands. The antigen epitope defined by MAb 12C3 was present on a glycoprotein with a molecular mass of 200 kDa and did not exhibit any cross reactivity with other well-known tumor markers. These data suggest that MAb 12C3 may be a useful tool for the immunohistologic detection of early malignant changes in epithelial ovarian tumors. In addition, MAb 12C3 also may facilitate a differential diagnosis between benign and borderline malignancies. PMID- 7872251 TI - Endoscopic biopsies and cytologic brushings of the esophagus are diagnostically complementary. AB - It is traditionally taught that concurrently obtained endoscopic tissue biopsies and cytologic brushings from the esophagus are diagnostically complementary. This contention is supported mostly by studies that involve only a small subset of patients (ie, those clinically thought to have an upper gastrointestinal neoplasm). Only a few investigations have examined the role of these paired specimens in the general patient population. Two hundred twenty-two consecutive esophageal biopsies and brushings obtained during the same endoscopic session were retrospectively reviewed. The same or a similar diagnosis was made for both specimen types in 166 (74.8%) of the specimen pairs. Among these pairs with diagnostic agreement, the most frequent diagnosis included Barrett's metaplasia (46), Candida esophagitis (37), and morphologically nonspecific inflammation (47). Nine squamous cell carcinomas and six adenocarcinomas were also detected in this subset. Diagnostic differences existed among 56 (25.2%) of the pairs. The most common diagnosis in this subset was Candida esophagitis. This fungus was present in 27 brushings, but not in the concurrently obtained biopsies. Two squamous cell carcinomas and one adenocarcinoma were diagnosed by cytology but not by biopsy. One squamous cell carcinoma was found only in the biopsy specimen. In the esophagus, brushings and biopsies are truly complementary for the detection of both neoplastic and inflammatory conditions. PMID- 7872252 TI - Tumor type is a determinant of susceptibility to apoptosis. AB - Little quantitative data exist on the extent of apoptosis (genetically-mediated cell deletion) in different human tumor types. Hematoxylin and eosin-stained paraffin sections of 102 malignant tumors (58 types) were evaluated for apoptotic cells and apoptotic bodies, using the 40x objective with a calibrated eye-piece and avoiding necrotic zones. The percentage of apoptotic cells and apoptotic bodies in the total number of tumor cells examined was designated as the apoptotic index (AI) for each case. There was a wide range in the AI for different tumor types: 45 tumors had AI < 1% and 93 had an AI of < 7%. In 107 additional tumors (11 types), the AI was determined to be within the same low, intermediate, or high range as the index cases. Apoptotic nuclear material was usually more prominent than mitoses. These results suggest that each tumor type has a characteristic AI that reflects innate tumor cell susceptibility to undergo apoptosis. Additional data are needed to determine whether significant variations in AI correlate with altered proliferative indices, aberrant oncogene/tumor suppressor gene expression, and standard clinicopathologic variables. PMID- 7872253 TI - The role of Epstein-Barr virus in lymphoepithelioma-like carcinomas. AB - Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a variety of lymphoproliferative disorders and several epithelial neoplasms, including undifferentiated nasopharyngeal carcinoma (UNPC; lymphoepithelioma). Lymphoepithelioma-like carcinomas (LEC) are tumors with morphologic features identical to UNPC that occur outside the nasopharynx. To determine whether EBV is associated with LEC, the authors conducted a comprehensive literature review of all pathologically documented LEC reported to date in the English literature. In summary, EBV is associated consistently with LEC from only four anatomic sites: stomach, salivary gland, lung, and thymus. Racial and/or geographic factors influence the association of EBV with LEC in some of these organs. Specifically, the association of EBV with LEC of the salivary gland and lung is restricted to Asian patients, whereas the association of EBV with gastric and thymic LEC is independent of race. The presence or absence of EBV in LEC does not appear to be prognotically important in those cases studies to date. PMID- 7872254 TI - Evaluation of the automated Bact-Alert system for pediatric blood culturing. AB - The Organon Teknika BacT/Alert (Organon Teknika, Durham, NC), using the Pedi-BacT 20 mL aerobic bottle (BPBCS) was compared to the Wampole Isolator (WI) 1.5 Microbial tube (Wampole Laboratories, Cranbury, NJ), for detection and recovery of pediatric pathogens. The BPBCS continuously monitors culture bottles for changes in CO2 concentrations, while WI cultures are examined twice daily for appearance of colonial growth on agar media. Of 5,175 paired blood cultures, 383 pathogens were recovered from 606 positive cultures. There were 272 pathogens recovered by both systems, 64 from BPBCS only, and 47 from WI only. Overall recovery rates were 88% for BPBCS and 83% for WI. There was no significant difference between the two systems in detection or times to positivity of staphylococci, Enterobacteriaceae, or pseudomonads. Trends toward better recovery of streptococci (20 vs. 10) and fastidious microaerophiles (3 vs. 0) were found with BPBCS, whereas more slowly growing pathogens (Rochalimaea henselae [1], Mycobacterium avium-intracellulare [1]) were recovered by WI only, but because of their lower frequency did not achieve statistical significance. Detection of Haemophilus influenzae (14.9 hours in WI vs. 45.4 hours in BPBCS) was faster with WI. False positive plus contaminant cultures were detected in 5.9% BPBCS versus 1.5% WI. BPBCS offers detection of bacteremia at a rate comparable to WI with advantages of automation. PMID- 7872255 TI - Immunohistochemical identification of perforin-positive cytotoxic lymphocytes in graft-versus-host disease. AB - To study the role of functionally active cytotoxic lymphocytes in human graft versus-host disease (GVHD), perforin expression in infiltrating mononuclear cells was immunohistochemically investigated in skin biopsy specimens. Perforin is a component of intracytoplasmic granules of cytotoxic lymphocytes and serves as a specific marker of functionally active cytotoxic lymphocytes. The study included two cases of transfusion-associated GVHD, seven cases of acute GVHD and five cases of lichenoid chronic GVHD after allogeneic bone marrow transplantation. All specimens obtained from transfusion-associated GVHD and one case of acute GVHD with extracutaneous involvement contained a significant number of perforin positive lymphocytes. In contrast, perforin-positive lymphocytes were few or absent in the other six cases of acute GVHD and in all five cases of lichenoid chronic GVHD after bone marrow transplantation. These findings suggest that perforin-mediated cytolysis by cytotoxic lymphocytes may be a major effector mechanism in transfusion-associated GVHD and at least in some cases of acute GVHD after bone marrow transplantation. PMID- 7872256 TI - Reactive versus neoplastic monocytoid B-cell proliferations. In situ hybridization study of immunoglobulin light chain mRNA. AB - To distinguish reactive versus neoplastic monocytoid B-cell (MBC) proliferations, the clonality of MBC was examined in paraffin-embedded tissues by in situ hybridization (ISH) of immunoglobulin (Ig) light chain messenger RNA (mRNA) with sensitive oligonucleotide probes in 26 cases. They included 13 cases of lymphadenitis with MBC reaction and 13 cases of nodal (n = 8) and extranodal (n = 5) monocytoid B-cell lymphoma (MBCL). Two cases represented a composite lymphoma showing a centroblastic-centrocytic and MBCL component. The clonality of MBC infiltrates could be demonstrated in 16 of 26 (61.5%) cases by immunostaining for Ig light chains and in all (100%) cases by ISH. Neoplastic MBC usually expressed a faint-to-moderate light chain restriction of mRNA, whereas some MBC (10% to 30% of total MBCL population) showed a strong positivity irrespective of plasmacytoid differentiation as indicated by Ig immunostaining (present in 9 of 13 cases). Reactive MBC expressed a faint kappa and lambda light-chain mRNA positivity. Five percent to 20% of total reactive MBC showed also a strong positivity for both Ig light chain mRNA, although only a minor part of these cells (7 of 13 cases) expressed polyclonal Ig by immunohistochemistry. These results indicate that (1) both reactive and neoplastic MBC can differentiate into plasma cells; and (2) a relatively high percentage of reactive and neoplastic MBC show a detectable mRNA transcription, but not a corresponding Ig synthesis. Either the Ig detection is not sensitive enough or these cells might be in an early differentiation phase, where the Ig production has not yet started. PMID- 7872257 TI - Ethylenediamine tetraacetic acid-associated leukoagglutination. AB - Three cases of ethylenediamine tetraacetic acid (EDTA)-induced leukoagglutination noted on peripheral blood films are reported. Two cases of EDTA-induced agglutination of benign lymphocytes, and one case of EDTA-induced mature neutrophil satellitosis about immature neutrophil were observed. EDTA-induced agglutination of malignant lymphoid cells has been reported in blood films from patients with malignant lymphoma and chronic lymphocytic leukemia. Our two cases are the first reported instances of EDTA-induced agglutination of benign lymphocytes. EDTA-induced agglutination of neutrophils is a well recognized, but uncommon event. This case was unusual because mature neutrophils were rosetted about a central immature granulocyte and no agglutination of mature neutrophils was noted. PMID- 7872258 TI - Pure red cell aplasia associated with thymic lymphoid hyperplasia and secondary erythropoietin resistance. AB - Systemic disorders, often immune in nature, can sometimes be associated with the presence of thymic pathology. Thymic enlargement due to lymphoid hyperplasia or thymoma is a common occurrence in patients with myasthenia gravis. In patients with pure red cell aplasia, at least 10% to 15% of patients are found to have thymoma, usually of spindle cell or medullary type. Pure red cell aplasia with demonstrable thymic enlargement due to lymphoid follicular hyperplasia is distinctly unusual, and has not been previously reported. The authors report such a case developing in a patient with end-stage renal failure maintained on hemodialysis and erythropoietin therapy. Because the red cell aplasia resolved after thymectomy, the disease process was considered etiologically related to the reactive lymphoid hyperplasia. PMID- 7872259 TI - B-cell chronic lymphocytic leukemia followed by high grade T-cell lymphoma. An unusual variant of Richter's syndrome. AB - A 70-year-old woman with a 2-year history of B-cell chronic lymphocytic leukemia (CLL) developed headache, fever, chills, and weakness. Bone marrow examination revealed both CLL and large cell immunoblastic lymphoma (Richter's syndrome). As expected, the CLL was of B-cell lineage. The neoplasm expressed low-density monotypic IgM lambda, the pan-B-cell antigens CD19, CD20, and CDw75, and the CD5 and CD43 antigens. The large cell immunoblastic lymphoma was of T-cell lineage, positive for the CD45RB, CD3, CD45RO, and CD43 antigens, and negative for the CD20 and CDw75 antigens. Both neoplastic components were negative for Epstein Barr virus RNA and latent membrane protein. Although 3% to 5% of patients with B cell CLL may develop higher-grade lymphoma, usually the lymphoma is of B-cell lineage and often represents a histologic manifestation of clonal evolution. Less commonly, B-CLL patients may develop transformation to a higher grade tumor that resembles Hodgkin's disease. Both the usual form of Richter's syndrome and particularly the Hodgkin's variant of Richter's syndrome may be associated with Epstein-Barr virus. Patients with B-cell CLL rarely develop a higher grade lymphoma of T-cell lineage. To our knowledge, only one other example has been reported in the literature. Epstein-Barr virus was not associated with either neoplasm in this case. PMID- 7872260 TI - DNA typing of the human MN and Ss blood group antigens in amniotic fluid and following massive transfusion. AB - Although red blood cell (RBC) antigen typing by agglutination is generally useful, several situations exist where this approach is difficult or impossible. For example, following a massive transfusion, a patient's residual RBCs are mixed with transfused normal donor RBCs. In this case, typing by hemagglutination primarily detects the antigens on the heterogeneous population of transfused RBCs. Agglutination testing is also of limited use for determining the phenotype of a fetus at risk for hemolytic disease of the newborn because fetal RBCs must be obtained by periumbilical blood sampling. Determining the genotype of an individual by analyzing genomic DNA isolated from peripheral blood nucleated cells or amniocytes is an alternative approach for determining the RBC antigen type. In this report, the allele specific polymerase chain reaction (AS-PCR) was used to identify the alleles at the MN and Ss loci that encode the corresponding antigens on glycophorin A (GPA) and glycophorin B (GPB), respectively. This method was used to type these alleles in peripheral blood samples obtained from normal individuals and from patients following massive transfusion. Of 23 peripheral blood specimens analyzed, all were correctly typed by this method. The allele specific polymerase chain reaction was also used to determine these alleles using amniotic fluid samples. Of 11 amniotic fluid specimens analyzed, 8 were correctly typed at both loci. Mistyping of three amniotic fluid specimens was explained by possible maternal blood contamination. PMID- 7872261 TI - The value of plasma calibrants in correcting coagulometer effects on international normalized ratios. An international multicenter study. AB - A study of lyophilized plasma calibrants in correcting for coagulometer effects on International Normalized Ratios (INR) has been conducted in an international survey. Prothrombin times were performed with the calibrants on 2 "common" thromboplastins and in-house thromboplastins in 3 brands of coagulometer at 37 centers. The International Sensitivity Indices (ISI) of 95 local systems with the calibrants were derived. The "true" INR of 10 test plasmas from warfarin-treated patients were established centrally using thromboplastin International Reference Preparations (IRP). International Normalized Ratios of these plasmas for each center were calculated using both the manufacturers' stated and the local ISI. The mean deviation of the 95 systems from the "true" INR of the warfarin plasmas was +14.4% with the manufacturers' ISI, but reduced to +1.04% with the local ISI. Local ISI determination with the calibrants avoids many of the difficulties of conventional thromboplastin calibrations. Plasmas from patients on warfarin and parallel manual PT with thromboplastin IRP are not required. PMID- 7872262 TI - A comparison of lyophilized artificially depleted plasmas and lyophilized plasmas from patients receiving warfarin in correcting for coagulometer effects on international normalized ratios. AB - The comparative value of lyophilized artificially depleted plasmas and plasmas from warfarin-treated patients in local (thromboplastin/coagulometer) system International Sensitivity Indices (ISI) determination has been studied at 39 centers in an international collaborative study. At each center, both types of plasmas were tested with two common thromboplastins (low ISI RecombiPlasTin and high ISI OBT), and in-house reagents using three brands of coagulometers. In 95 local systems, they was agreement. With both thromboplastins, coagulometers lowered the ISI from the manual or stated ISI with all systems. Differences between the two types of lyophilized plasmas with the two common thromboplastins were not of clinical importance. Artificially depleted plasmas are easier to obtain in sufficient volumes than plasma from warfarin-treated patients, and more easily provide the wide range of INR values required for reliable local ISI calibration. The agreement between the two types of lyophilized calibrant is reassuring. PMID- 7872263 TI - Comparative safety of blood collection in "high-risk" autologous donors versus non-high-risk autologous and directed donors in a hospital setting. PMID- 7872264 TI - Antigen density in B-cell chronic lymphocytic leukemia. PMID- 7872265 TI - Clinically appropriate investigations in cases of suspected lupus anticoagulant. PMID- 7872266 TI - Relating a history of abuse to gastrointestinal disease: empowering the physician and the patient. PMID- 7872267 TI - Should a normal-appearing colorectal mucosa be biopsied? PMID- 7872268 TI - Is the risk of cancer in ulcerative colitis increasing? PMID- 7872269 TI - Gastric carcinoid tumors: the biology and therapy of an enigmatic and controversial lesion. AB - Gastric carcinoid tumors were previously believed to be rare lesions, representing less than 2% of all carcinoid tumors and less than 1% of all stomach neoplasms. More recent studies have demonstrated that they may constitute as much as 10-30% of carcinoid tumors. Patients with conditions associated with hypergastrinemia, such as chronic atrophic gastritis, Zollinger-Ellison syndrome with multiple endocrine neoplasia type 1 (ZES-MEN-1), and pernicious anemia, display a markedly elevated incidence of gastric carcinoid tumor formation. A classification system distinguishing three types of gastric carcinoid tumor has been proposed: 1) tumors associated with chronic atrophic gastritis, 2) tumors associated with Zollinger-Ellison syndrome, and 3) sporadic lesions. Tumors that develop in association with hypergastrinemia are usually composed of enterochromaffin-like (ECL) cells, in contrast to sporadic lesions that contain a variety of endocrine cell types (enterochromaffin, ECL, X). In both intact animal models such as the rat and Praomys (mastomys) natalensis and in isolated purified ECL cell preparations, gastrin has been demonstrated to exert a powerful trophic effect on ECL cells, in addition to stimulating histamine secretion. It is apparent that hypergastrinemia-associated gastric carcinoids display relatively benign biological behavior. Sporadic lesions require aggressive surgical management on diagnosis. Type I and type II (hypergastrinemia-associated) lesions can be managed initially by endoscopic excision of accessible tumors, followed by endoscopic surveillance. If tumors recur, antrectomy and local excision may be used to remove the source gastrin, resulting in cure in the vast majority of patients. PMID- 7872270 TI - Colonoscopy: a review of its yield for cancers and adenomas by indication. AB - Colonoscopy for bleeding indications (positive fecal occult blood test, emergent or nonemergent rectal bleeding, melena with a negative upper endoscopy and iron deficiency anemia) has a substantial yield for cancers (1 per 9 to 13 colonoscopies), although slide rehydration of fecal occult blood tests decreases the yield (1 per 45 colonoscopies). Prospective studies indicate that nonbleeding colonic symptoms have a substantially lower yield for cancer than bleeding symptoms (1 per 109 colonoscopies). Patients with indications for screening colonoscopy with a relatively high yield of cancer are those with Lynch syndrome (1 per 39 colonoscopies) and males more than 60 yr old (1 per 64 colonoscopies). Perioperative colonoscopy in persons undergoing colorectal cancer resection has a high yield for synchronous cancer (2-3%). An initial examination in persons with long-standing ulcerative colitis has a high yield for cancer (12%). Surveillance colonoscopy after cancer resection has an intermediate yield for anastomotic cancer (1 per 74 procedures) and metachronous cancers (1 per 82 colonoscopies), although this number may overestimate the yield of metachronous cancer. Postpolypectomy surveillance and ulcerative colitis surveillance colonoscopy have relatively low yields for cancer (1 per 317 and 360 colonoscopies, respectively). However, postpolypectomy surveillance colonoscopy, in combination with initial clearing colonoscopy, has been proven to be almost entirely effective in preventing colorectal cancer death. Further, cancer yields for postpolypectomy surveillance should improve with implementation of new surveillance guidelines, with little or no impact on mortality. The effectiveness of ulcerative colitis surveillance is less certain. Referral of patients with low-grade dysplasia for colectomy would improve the value and effectiveness of surveillance colonoscopy in ulcerative colitis. Adenoma yields at colonoscopy are relatively independent of indication, as evidenced by the high yield of adenomas in screening colonoscopy studies. Demographic factors, including increasing age and male gender, are important predictors of adenomas at initial colonoscopy. Age, male gender, and multiple and large adenomas at initial examination are predictors of adenomas at subsequent postpolypectomy surveillance. Persons with ureterosigmoidostomies can be screened by interval flexible sigmoidoscopy and do not require screening colonoscopy. A history of breast cancer does not predict an improved yield of colonoscopic screening compared to average-risk persons. PMID- 7872271 TI - Self-reported abuse and gastrointestinal disease in outpatients: association with irritable bowel-type symptoms. AB - OBJECTIVE: A link between functional bowel disease and sexual, physical, emotional, or verbal abuse remains controversial. We aimed to determine whether abuse is associated with functional bowel disease in outpatients. METHODS: A consecutive sample of outpatients completed a validated questionnaire; 997 responded. Using standard criteria, we obtained data on symptoms, psychosocial factors, and abuse (sexual, physical, and emotional or verbal). Logistic regression analysis was used to determine whether abuse was associated with functional bowel disease (versus organic disease) and with irritable bowel syndrome (IBS)-type symptoms defined by the Manning criteria. Adjustments were made for age, gender, marital status, education level, psychological distress, and social support. RESULTS: Of those with a physician-based diagnosis of functional bowel disease (n = 440), 22% reported some form of abuse (13% sexual and/or physical abuse), compared with those with organic disease (n = 557), 16% of whom reported some form of abuse; this difference was not significant. However, abused patients were significantly more likely to report IBS-type symptoms than those who did not report a history of abuse (odds ratio = 1.7, 95% confidence interval = 1.2, 2.5). CONCLUSION: Outpatients who report abuse are more likely to have IBS-type symptoms. PMID- 7872272 TI - Chronic, unexplained diarrhea: are biopsies necessary if colonoscopy is normal? AB - OBJECTIVE: We sought to determine the frequency of clinically important histological abnormalities in patients with chronic, unexplained diarrhea who had macroscopically normal colonic endoscopies. METHODS: Of 855 consecutive patients undergoing colonoscopy (595 cases) or flexible proctosigmoidoscopy (260 cases) by one endoscopist, biopsies were taken in 111 cases of unexplained diarrhea of at least 4-6 weeks duration in which the colorectal mucosa appeared grossly normal. All biopsies were blindly reviewed by one pathologist. RESULTS: In this group of patients with macroscopically normal colons, we identified no cases of Crohn's disease or ulcerative colitis or any definite cases of collagenous colitis (CC) or lymphocytic colitis (LC). There was one case classified as "possible CC" and 13 cases classified as "some features of LC". There were five cases of melanosis coli, one case of cytomegalovirus colitis (in an immunosuppressed patient), and one case of radiation injury. Ninety-one cases were classified as no pathological diagnosis or minimal histological change. Patients with abnormal histology were contacted to see if they had persistence or resolution of diarrhea. For the cases of "possible CC" and "some features of LC," diarrhea had resolved spontaneously in the majority. Interesting to note, only one of the five melanosis coli patients admitted to laxative use, raising the question of surreptitious abuse. CONCLUSIONS: We conclude that the yield of biopsies in diarrhea patients with macroscopically normal colons at endoscopy is low. It may be reasonable to obtain biopsies in patients with relatively severe or debilitating symptoms, with diarrhea that sounds "organic" (e.g., nocturnal stools, frequent watery stools, weight loss, elevated sedimentation rate), or in patients who are immunosuppressed. When biopsies are taken at colonoscopy, we suggest taking about six from throughout the colon and placing them into just one specimen container to help minimize costs. PMID- 7872273 TI - Worsening risk for the development of dysplasia or cancer in patients with chronic ulcerative colitis. AB - OBJECTIVES: Patients with ulcerative colitis (UC) are at increased risk for developing dysplasia or cancer (neoplasia) and are usually offered colonoscopic surveillance to reduce their risk of cancer-related mortality. The causes of neoplasia may be related to features of UC (the extent, severity, activity, and age at onset of the disease) and to environmental factors (medications, vitamin and mineral supplementation, diet, or industrial pollutants). To determine whether and how the risk (and hence the risk factor profile) for the development of neoplasia changes over time, we conducted an historical cohort study. METHODS: From 445 adult patients with UC proximal to the splenic flexure seen in the Department of Gastroenterology between 1986 and 1992, a random sample of 209 patients was selected. Patients with UC for less than 8 yr or colectomy or neoplasia detected within 2 yr of referral were excluded, leaving 98 patients in the cohort, half of whom had disease onset during or before 1972. RESULTS: After controlling for age at disease onset and duration of disease at first colonoscopy, we found that patients with an earlier year of disease onset were 85% less likely to develop neoplasia than patients with a later year of disease onset (hazard rate ratio 0.15, 95% confidence interval 0.03-0.66). CONCLUSION: These data suggest that the risk for developing neoplasia in UC patients increases with increasing calendar year, implying a worsening risk factor profile. PMID- 7872274 TI - Olsalazine versus sulphasalazine for relapse prevention in ulcerative colitis: a multicenter study. AB - OBJECTIVE: To compare the relapse-preventing effect and the frequency of adverse events of olsalazine and sulphasalazine in sulphasalazine-tolerant patients with ulcerative colitis. METHODS: Patients in remission, with at least two episodes of active disease during the last 5 yr, were randomized to 2 g of sulphasalazine or 1 g of olsalazine daily and were followed for 6-18 months. Relapse rates in the two groups were compared using frequency and life-table analysis. Sixty-nine patients with proctitis, 140 with left-sided colitis, and 113 with subtotal or total colitis were evaluated. RESULTS: In the intention-to-treat analysis, the failure rate (relapses plus withdrawals) was 54.7% in the olsalazine and 47.2% in the sulphasalazine group. In the per-protocol analysis excluding withdrawals, 44.7% relapsed in the olsalazine and 39.3% in the sulphasalazine group. Remission curves did not differ significantly, although at all time intervals the frequency of remission was slightly higher in the sulphasalazine group (p = 0.19 in the intention-to-treat analysis and p = 0.42 in the per-protocol analysis estimated by the log-rank test). Twelve patients (of whom five had diarrhea) in the olsalazine group versus eight patients in the sulphasalazine group discontinued the study because of side effects. CONCLUSION: The relapse-preventing effect of olsalazine and sulphasalazine in sulphasalazine-tolerant patients did not differ. Furthermore, the tolerability of olsalazine, particularly concerning diarrhea, appears to be better than previously reported. PMID- 7872275 TI - The forms and the levels of fecal PMN-elastase in patients with colorectal diseases. AB - OBJECTIVES: To compare the form of polymorphonuclear leukocyte (PMN)-elastase in feces with that in plasma and to investigate the usefulness of measuring fecal PMN-elastase levels in patients with colorectal diseases. METHODS: We examined PMN-elastase complexed with alpha 1-antitrypsin (alpha 1-AT), chymotrypsin, and alpha 2-macroglobulin by ELISA in feces and plasma. Fecal levels of total PMN elastase were determined in patients with colonic polyp (N = 19), colonic cancer (N = 20), ulcerative colitis (UC; N = 36), colonic Crohn's disease (CD; N = 26), and in control subjects (N = 20). RESULTS: Most PMN-elastase was not complexed with alpha 1-AT, chymotrypsin, or alpha 2-macroglobulin in feces, whereas most plasma PMN-elastase was complexed with alpha 1-AT. Fecal concentrations and daily fecal excretion of PMN-elastase were significantly increased in patients with active UC (medians 54.8 micrograms/g, 15.14 mg/day) and active CD (41.5 micrograms/g, 10.24 mg/day) compared to those values in control subjects (0.6 micrograms/g, 0.11 mg/day) and in patients with colonic cancer (2.5 micrograms/g, 0.33 mg/day). In inactive UC and CD, these values (3.4 micrograms/g, 0.52 mg/day and 5.2 micrograms/g, 0.59 mg/day, respectively) were significantly lower than in active UC and CD, respectively. In UC, all patients whose rectal biopsies showed infiltration of PMN had high fecal PMN-elastase levels. CONCLUSIONS: Our results suggest that the measurement of fecal PMN-elastase concentrations are useful for monitoring the disease activity of UC and CD, especially when evaluating whether intestinal inflammation has disappeared completely. PMID- 7872276 TI - Screening for celiac disease: a prospective study on the value of noninvasive tests. AB - OBJECTIVE: Celiac disease is frequently diagnosed in patients with nonspecific abdominal symptoms. Therefore, highly sensitive, specific, and simple noninvasive screening tests are needed. METHODS: This study compared the usefulness of IgG- and IgA-antigliadin antibodies, IgA-endomysial antibodies, and intestinal permeability in diagnosing celiac disease in 102 adult patients with nonspecific abdominal symptoms. In addition, all patients underwent small bowel biopsy as a gold standard for the diagnosis of celiac disease. RESULTS: Forty-nine patients were ultimately diagnosed as having celiac disease because of flat mucosa. Flatulence and signs and symptoms dating back to childhood were more frequent and abdominal pain less frequent (p < 0.05) in celiac disease but were not helpful for screening. IgA-endomysial antibodies showed a sensitivity and specificity of 100%; an altered intestinal permeability had also a 100% sensitivity, but only 55% specificity. IgG- and IgA-antigliadin antibodies' sensitivity (73% and 82%, respectively) and specificity (74% and 83%, respectively) were much lower. Combining the two antigliadin antibodies did not significantly improve the sensitivity and specificity. CONCLUSIONS: Our data show the advantage of IgA endomysial antibodies for screening of celiac disease except in the case of patients with IgA-deficiency or dermatitis herpetiformis. In these patients, the permeability test could improve noninvasive differential diagnosis. PMID- 7872277 TI - Incidence of peptic ulcer in men is inversely correlated with blood pressure: study in an apparently healthy Japanese population. AB - OBJECTIVE: To study the role of autonomic nervous innervation in the etiology of peptic ulcer, we investigated the blood pressure in patients with peptic ulcer. METHODS: In 100,085 Japanese adults who were undergoing health screening examinations, including barium meal study, there were endoscopic evaluation confirmed diagnoses of gastric ulcer in 769 cases and of duodenal ulcer in 344 cases. The blood pressure in those patients was compared with that in 57,208 normal Japanese controls with no gastrointestinal abnormalities, as confirmed by barium meal study. RESULTS: The blood pressure of younger and middle-aged men with gastric and duodenal ulcer were lower than those of normal control men. In women, except for the diastolic pressure of those in their 50s, the blood pressure in patients with peptic ulcer and normal controls did not differ significantly. The incidence of duodenal ulcer or of gastric ulcer in men was inversely related to the systolic and diastolic pressure. No definite relationship in this respect was seen in women. CONCLUSIONS: An inverse relationship was observed between the occurrence of peptic ulcer and the blood pressure level in Japanese men, but not in women. The relationship may be mediated by an inhibitory effect of the sympathetic nervous system on ulcer formation in hypertensive subjects. The reason for the sex difference in this respect is unknown. PMID- 7872278 TI - Azithromycin triple therapy for Helicobacter pylori infection: azithromycin, tetracycline, and bismuth. AB - BACKGROUND: Azithromycin is new acid-stable macrolide that achieves 10- to 40 fold higher tissue levels than erythromycin after oral dosing. Important to note, the tissue half-life of azithromycin is measured in days instead of hours. METHOD: We evaluated two new triple therapies for Helicobacter pylori infection in which azithromycin was substituted for metronidazole either as 250 mg b.i.d. or t.i.d. along with tetracycline 500 mg q.i.d. and bismuth subsalicylate 2 tablets q.i.d. for 14 days. H. pylori status was determined by histology before and 6 wk or more after therapy. RESULTS: Thirty men with documented H. pylori peptic ulcers completed therapy. Twenty-one also received ranitidine (300 mg in the evening) along with the antimicrobial therapy. H. pylori infection was successfully treated in 15 (50%) (95% CI = 31-69%). The cure rate was significantly higher with the 250-mg-t.i.d.-azithromycin dosage regime (83%) (95% CI = 52-98%) compared to the 250-mg-b.i.d.-dosage regime (28%) (95% CI = 10-53%) (p < 0.01). Troublesome side effects were experienced by the majority of those receiving azithromycin t.i.d. CONCLUSION: We conclude that although 750 mg or more of azithromycin might eventually be able to replace metronidazole or clarithromycin in standard triple therapy, additional studies are required to identify a regime that is both effective and tolerable. PMID- 7872279 TI - Effects of Helicobacter pylori infection on healing and recurrence of gastric ulcers. AB - OBJECTIVES: The effects of Helicobacter pylori infection on the healing and recurrence of gastric ulcers were investigated. METHODS: Eighty-five and 17 patients with endoscopically-proven gastric ulcer with and without H. pylori infection, respectively, received 800 mg of cimetidine daily. Healing of ulcer and H. pylori infection were assessed at wk 12. After the 12-wk-treatment period, 67 and 16 patients with healed ulcer positive and negative for H. pylori infection, respectively, received maintenance treatment (cimetidine 400 mg daily). Ulcer recurrence and H. pylori infection were assessed at or within 24 wk from the beginning of maintenance treatment. Variables influencing ulcer healing and recurrence were analyzed by multiple regression analysis. RESULTS: Ulcer healing at wk 12 was similar in patients with and without H. pylori infection, occurring in 16 (89%) of 18 patients without H. pylori infection, compared with 67 (87%) of 77 patients with H. pylori infection. At or within 24 wk from the start of maintenance therapy, ulcer recurrence was significantly more frequent in patients with H. pylori infection than in those without: it occurred in three (20%) of 15 patients without H. pylori infection, but in 37 (58%) of 64 patients with infection. Multiple regression analysis showed that H. pylori infection was related most closely to ulcer recurrence independently. CONCLUSION: H. pylori infection had a significant independent influence on gastric ulcer recurrence, but not initial ulcer healing. PMID- 7872281 TI - Endoscopic aspiration lumpectomy of esophageal leiomyomas derived from the muscularis mucosae. AB - OBJECTIVES: There is still much debate about the indications and best technique for endoscopy for the treatment of esophageal leiomyomas. We developed a novel technique for endoscopic aspiration lumpectomy and used it in patients with esophageal leiomyomas derived from the muscularis mucosae. METHODS: Nine patients with esophageal leiomyomas were treated with informed consent. The indication for intervention was based on the endosonographic confirmation of a tumor originating from the 2nd layer of the esophagus. We attached a transparent cylinder to the tip of an endoscope and a snare-guide tube to the outer axis of the scope. After endoscopic suction of the tumor into the cylinder, the snare was pushed open. The tumor was grabbed at its base with the entire surrounding mucosa, and removed. RESULTS: The overall procedure time averaged 18 minutes, and there were no complications in any of the subjects. The resected specimens were elliptical with a mean long diameter of 22 +/- 4 mm and a mean short diameter of 17 +/- 4 mm. Complete resection was possible in eight of the nine tumors that were under 2 cm in diameter. After a follow-up period of 4 to 27 months (mean 11 months), no recurrence was found in any of the completely resected cases. CONCLUSIONS: Endoscopic aspiration lumpectomy has been proven to be a safe, effective, and less invasive procedure for small esophageal leiomyomas derived from the muscularis mucosae. PMID- 7872280 TI - Gastrospirillum hominis ("Helicobacter heilmanii"): a cause of gastritis, sometimes transient, better diagnosed by touch cytology? AB - OBJECTIVE: Besides Helicobacter pylori, another spirillar microorganism, provisionally called Gastrospirillum hominis, has been described in the human stomach in association with gastritis. The aim of this study was to assess the role of cytology in the diagnosis, to assess the gastritis associated with this infection, and to approach its natural history. METHODS: Charts and endoscopic biopsies and smears (touch cytology) from 28 patients with G. hominis seen between 1986 and 1992 were reviewed and compared with biopsies and smears from 28 patients with H. pylori gastritis. RESULTS: G. hominis was seen on smears from all 28 patients but diagnosed in only 15 of the corresponding sets of biopsies. No patient had evidence of H. pylori colonization. All patients had chronic antral gastritis with lymphoplasmocytes, and neutrophils were present in 13 patients. In addition, reactive changes were frequent: foveolar hyperplasia (n = 25), vasodilation (n = 23), lamina propria edema (n = 23), and increased intracytoplasmic mucin (n = 19). In contrast, intestinal metaplasia (n = 3) and glandular atrophy (n = 2) were infrequent, and lymphoid nodules were not seen. In patients with H. pylori, reactive changes were mild, and the lymphoplasmocytic infiltration was more intense (p < 0.005). Eleven patients had at least two endoscopic examinations with biopsies, with persistent colonization in only four. Seven patients cleared the infection with a concomitant regression of gastritis. CONCLUSIONS: G. hominis is more often detected in smears than biopsies. It is seen in association with a peculiar form of gastritis-associating chronic and reactive changes. Colonization may be a transient phenomenon and is never associated with H. pylori. PMID- 7872282 TI - Cisapride for gastroesophageal reflux disease: a placebo-controlled, double-blind study. AB - OBJECTIVES: To evaluate the safety and efficacy of cisapride in patients with gastroesophageal reflux disease. METHODS: Patients (N = 177) were randomized to double-blind treatment with cisapride (10 or 20 mg q.i.d.) or placebo for 12 wk. Efficacy was determined by pre- and poststudy endoscopies, symptom assessments by patient and physician, and Maalox consumption. Safety evaluations included vital signs, electrocardiograms, clinical laboratory tests, and reports of adverse events. RESULTS: Cisapride 10 mg significantly reduced daytime and nighttime heartburn at 4 wk compared with placebo. Cisapride 20 mg reduced both daytime and nighttime heartburn at 4, 8, and 12 wk, compared with placebo, and was also significantly superior to the 10-mg dose at 12 wk. The percent of patients with endoscopic healing was significantly higher with cisapride 20 mg than with placebo [healing: 51 vs 36% (p < or = 0.044)]. Maalox usage declined significantly with cisapride 20 mg compared with placebo. No clinically significant changes in safety variables occurred with cisapride. The most frequently reported adverse events in the cisapride group were diarrhea, headache, and sinusitis. CONCLUSIONS: Cisapride 10 and 20 mg q.i.d. were safe and well tolerated in a population of patients with mild-to-moderate gastroesophageal reflux disease. Both symptoms and endoscopic grade improved after 12 wk of treatment with cisapride 20 mg q.i.d. PMID- 7872283 TI - Impedance planimetry: an integrated approach for assessing sensory, active, and passive biomechanical properties of the human esophagus. AB - OBJECTIVES: Our objective was to study the biomechanical properties and their relationships to the sensory and motor function of the esophagus, which has seldom been examined in humans. METHODS: We used impedance planimetry, to study these properties. This system measures cross-sectional area (CSA) and intraluminal pressure simultaneously and facilitates calculation of some of the biomechanical properties of the esophageal wall. We performed 15 studies in 12 healthy volunteers. In three subjects, the studies were repeated to test reproducibility. RESULTS: Stepwise increments in balloon pressure from 5 to 40 cm H2O induced an increase in CSA (mean +/- SD), 91 +/- 27 to 469 +/- 63 mm2, the wall tension 27 +/- 4 to 484 +/- 32 mm x cm H2O, and the strain 0.2 +/- 0.1 to 1.3 +/- 0.3. The tension/strain relationship increased exponentially. The compliance did not change. The threshold for first sensation was 30 +/- 11 cm H2O (mean +/- SD). In three subjects, when the balloon was distended > 40 cm H2O, chest pain was induced at a threshold of 62 +/- 3 cm H2O, and the compliance decreased. Balloon distension induced tertiary contractions and secondary peristalsis at thresholds of 15 +/- 4 cm H2O, and 19 +/- 5 cm H2O. Repeat studies showed good correlation (r = 0.9). CONCLUSION: Graded balloon distension increases esophageal CSA, wall tension, and strain. When a threshold is reached, tertiary contractions and secondary peristalsis develop at pressures less than 50% of sensory threshold. At higher pressures, chest pain is induced. Impedance planimetry promises to be a simple, objective, reproducible, and comprehensive technique for evaluating the sensory, motor, and viscoelastic properties of the esophagus. PMID- 7872284 TI - Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo. AB - OBJECTIVES: To determine the safety and efficacy of a new preventive agent for antibiotic-associated diarrhea (AAD) in patients receiving at least one beta lactam antibiotic. METHODS: A double-blinded, placebo-controlled, parallel group study was performed in a high-risk group of hospitalized patients receiving a new prescription for a beta-lactam antibiotic and having no acute diarrhea on enrollment. Lyophilized Saccharomyces boulardii or placebo (1 g/day) was given within 72 h of the start of the antibiotic(s) and continued until 3 days after the antibiotic was discontinued, after which the patients were followed for 7 wk. RESULTS: Of the 193 eligible patients, significantly fewer, 7/97 (7.2%), patients receiving S. boulardii developed AAD compared with 14/96 (14.6%) on placebo (p = 0.02). The efficacy of S. boulardii for the prevention of AAD was 51%. Using a multivariate model to adjust for two independent risk factors for AAD (age and days of cephalosporin use), the adjusted relative risk was significantly protective for S. boulardii (RR = 0.29, 95% CI = 0.08, 0.98). CONCLUSION: The prophylactic use of S. boulardii given with a beta-lactam antibiotic resulted in a significant reduction of AAD with no serious adverse reactions. PMID- 7872285 TI - Hepatic histopathological changes in biliary pancreatitis. AB - OBJECTIVES: Elevation of serum transaminase has been shown to establish gallstone etiology in acute pancreatitis, but little has been reported regarding hepatic histopathological changes in biliary pancreatitis. The main purposes of this study were to observe hepatic histopathological changes in the acute stage of biliary pancreatitis and to elucidate the mechanism of transaminase elevation. METHODS: Microscopic findings for liver biopsy specimens (26 patients) as well as gross pathological observations of the biliary tract at emergency operation were analyzed in 62 patients with biliary pancreatitis. RESULTS: The main light microscopic findings were hepatocyte necrosis (96.2%) and acute cholangitis (65.4%). The main electron microscopic findings (two patients) were disorganized liver cell plate, retention of biliary material in the dilated canaliculi, and shedding of cytoplasm into the space of Disse in some areas. At laparotomy, impacted and floating bile duct stones were found in 35 (56.5%) and 13 (21.0%) patients, respectively, and acute inflammatory biliary diseases were encountered in 43 (69.4%) patients. CONCLUSIONS: The main hepatic histopathological changes in biliary pancreatitis were acute inflammatory hepatocyte necrosis, hepatocyte degeneration, and acute cholangitis caused by ampullary stones impacted during their transpapillary passage. Serum transaminase elevation might be a reflection of hepatocyte necrosis and/or degeneration. PMID- 7872286 TI - Clinical usefulness of evaluation of portal circulation by per rectal portal scintigraphy with technetium-99m pertechnetate. AB - OBJECTIVE: Portal circulation, in particular the contribution of the inferior mesenteric vein, can be evaluated in a relatively noninvasive way by per rectal portal scintigraphy (J Nucl Med 1988; 29:460-5). The clinical usefulness of the method was evaluated. METHODS: A solution containing technitium-99m pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. By analyses of the curves, the per rectal portal shunt index (SI) was calculated. RESULTS: The SI was higher for disorders that were more severe, increasing in the order of chronic persistent hepatitis, chronic aggressive hepatitis, and cirrhosis, and the SI was higher in cirrhotic patients than in patients with chronic hepatitis or in healthy subjects. The SI was significantly higher when a complication (varices, ascites, or encephalopathy) was present. Correlation between the SI and classic indicators for functional reserve was significant. The SI was significantly related to survival according to results of regression analysis by Cox's proportional hazards model. On the basis of the SI when patients were first examined, the patients with cirrhosis were divided into three groups of roughly equal size: group A, SI under 30%; group B, SI between 30 and 70%; and group C, SI over 70%. The survival rate was lower in group B than in A, lower in group C than in A, and lower in group C than in B. CONCLUSIONS: This method is clinically useful, especially in establishing the prognosis. PMID- 7872287 TI - Gastric emptying is impaired in patients with spinal cord injury. AB - OBJECTIVES: The rate and completeness of gastric emptying (GE) are major determinants of the bioavailability of oral medication, and the efficiency of gastric emptying is highly dependent on an intact central nervous system. Hence, in spinal cord injury (SCI), an impairment in gastric emptying could significantly diminish drug efficacy. METHODS: We evaluated posture-dependent (seated and supine) gastric emptying of an isotopically-labeled liquid meal in six quadriplegic subjects. The time-course profile of the gastric elimination of a radionuclide was followed for up to 120 min using serial anterior scintigraphy, and the disappearance of radioactivity from the stomach was described by both a mono- and biexponential fit of raw data. A half-time of gastric emptying (GEt1/2) was estimated from each curve and compared to GEt1/2 derived from able-bodied (intact neuraxis) experimental and historic control populations. RESULTS: The mean GEt1/2 in quadriplegic subjects (monoexponential curve fit) was significantly increased to 43.4 +/- 26.0 min in seated SCI subjects (95% CI 13.5 73.2, p < 0.05) and to 50.5 +/- 48.0 min in supine SCI subjects compared to supine experimental and historic control values of 10.1 +/- 8.8 min (95% CI 2.3 18.0, p < 0.05) or 12.0 +/- 3.0 min (95% CI 9.4-14.8, p < 0.05), respectively. A small, non-significant trend towards an increased rate of GE (decreased GEt1/2) was observed in seated SCI subjects. CONCLUSIONS: We conclude that gastric emptying is impaired in subjects with cervical SCI. Comparative studies of gastric emptying in subjects with SCI should incorporate concurrently studied, control subjects and employ experimental methods that are not constrained by truncated data collection periods. The convention of forcing GE data to conform to a monoexponential pattern of evacuation ignores time-dependent multiphasic patterns of GE and does not support serendipity. PMID- 7872288 TI - Hereditary angioedema: an infrequent cause of abdominal pain with ascites. AB - Patients with hereditary angioedema have episodes of local swelling, usually affecting the face, extremities, upper airway, and gastrointestinal tract. Only infrequently does it cause recurrent abdominal pain (with or without ascites); however, because it has potentially life-threatening complications, an early diagnosis is important. We describe a case of type I hereditary angioedema (a quantitative deficit of C1 inhibitor), the sole initial symptom of which was severe recurrent and self-limited abdominal pain, accompanied by ascites during these episodes. During a 4-yr period of treatment with danazol, the patient was virtually asymptomatic, despite levels of C4 and C1 inhibitor that remained below normal limits, and there have been no major side effects that could be attributed to treatment with androgens. PMID- 7872289 TI - Pneumomediastinum after endoscopic sphincterotomy. AB - Pneumomediastinum is a rare complication of endoscopy that usually indicates free peritoneal or retroperitoneal perforation. We report an unusual case of self limiting pneumomediastinum after endoscopic sphincterotomy in which there was no radiological evidence of gut wall perforation. We postulate that this was due to interstitial tracking of air from the duodenal wall, and we discuss the possible pathophysiology. This complication should be recognized as distinct from pneumomediastinum associated with perforation, particularly as it appears to be benign and therefore does not require surgical or radiological intervention. PMID- 7872290 TI - Simultaneous right-sided volume overload and left-sided hypovolemia in a man with massive ascites and a hydrothorax. AB - The medical problems presented by an 83-yr-old man with hepatic amyloidosis complicated by massive ascites and a right hydrothorax are described. As a result of right atrial compression limiting right heart filling, the patient simultaneously experienced left-sided hypovolemia with renal and hepatic ischemia while manifesting signs of right-sided congestive failure. Only with a transjugular intrahepatic portosystemic shunt procedure, which eliminated the right atrial compression with resolution of the hydrothorax and ascites, was it possible to improve the other medical condition of this man. PMID- 7872291 TI - Primary lymphoma presenting as intra-abdominal mass and obstructive jaundice. AB - We reported a 67-yr-old man presenting with right hypochondrial pain, obstructive jaundice, and hepatic hilar mass. Biliary stenting relieved the jaundice. Percutaneous aspiration cytology of the mass was suspicious of lymphoma. He had no evidence of the disease, including lymphadenopathy, elsewhere in the body. Excision of the mass en bloc with cholecystectomy and right hemicolectomy confirmed the diagnosis of B-cell lymphoma. The patient recovered uneventfully and received nine courses of systemic chemotherapy afterward. Up to the time of writing, the patient remained disease-free 20 months after the initial presentation. This is the first case report of a primary lymphoma arising in and remaining localized to the hepatic hilar region. Moreover, it illustrates the importance of obtaining tissue diagnosis in patients with malignant jaundice. PMID- 7872292 TI - Malignant histiocytosis in a patient presenting with hepatic dysfunction and peliosis hepatis. AB - In this article, we report the case of a 36-yr-old patient presenting with manifestations of portal hypertension, hepatic dysfunction, and fever who proved to have peliosis hepatis on liver biopsy. A thorough work-up revealed no obvious etiology. At autopsy, malignant histiocytosis of the liver and bone marrow was diagnosed. This case represents the first report of the association of peliosis hepatis with this rare histiocytic neoplasm and exemplifies the need for persistence in the search for malignancy, particularly hematological malignancy, in the patient with unexplained peliosis. The clinical similarity of peliosis hepatis associated with hematological malignancy and bacillary peliosis is also discussed. PMID- 7872293 TI - Endoscopic, radiographic, and manometric findings in dysphagia associated with sarcoid due to extrinsic esophageal compression from subcarinal lymphadenopathy. AB - Esophageal dysphagia associated with sarcoid has been attributed to dysmotility from neuropathy, dysmotility from myopathy, mechanical obstruction from esophageal mural involvement, and mechanical obstruction from extrinsic compression by subcarinal lymphadenopathy. The relative importance of these etiologies has not been evaluated because of variable and nonstandardized analysis. In particular, manometry has not been performed to exclude esophageal dysmotility in dysphagia attributed solely to extrinsic compression. A 42-yr-old male with chronic sarcoid for 20 yr presented with mild dysphagia to solids. An upper gastrointestinal series revealed smooth narrowing of the esophageal lumen and transient hang-up of the barium column and a 1.3-cm diameter radiopaque pill at the level of the carina. Chest computerized tomography revealed esophageal narrowing at the level of the carina and splaying of the two mainstem bronchi from compression by subcarinal lymphadenopathy. Esophagogastroduodenoscopy revealed elliptical esophageal narrowing due to multiple, smooth, and nodular deformities at 29-32 cm from the incisors. Pathological examination of deep biopsies of the nodules revealed normal mucosa and submucosa without granulomas. Esophageal manometry revealed a highly localized high pressure zone of 39.8 +/- 6.1 mm Hg at 29-31 cm from the incisors (lab normal about -5 mm Hg). Esophageal muscle contractions were peristaltic and of normal amplitude above, within, and below this high pressure zone. This case report demonstrates that extrinsic compression from subcarinal lymphadenopathy is a sufficient mechanism for dysphagia with sarcoid, but it does not exclude a role for other mechanisms, such as nerve injury, in some cases. PMID- 7872294 TI - Deglutition disorder as a late sequel of radiotherapy for a pharyngeal tumor. AB - We present the case of a 62-yr-old patient who developed severe swallowing problems 5 yr after radiotherapy for a pharyngeal carcinoma. Although peripheral and cranial nerves are thought to be relatively radioresistant, cranial nerve damage can occur many years after radiotherapy. This may result in severe deglutition disorders and lead to a complete inability to eat normally. The aim is to demonstrate how these late sequelae can cause impairment of different structures involved in the swallowing process. PMID- 7872295 TI - Idiopathic colonic varices: an unusual cause of massive lower gastrointestinal hemorrhage. AB - We report a patient with massive lower gastrointestinal bleeding, probably from extensive colonic varices. Despite lengthy investigation, the etiology of the colonic varices was not determined. There are numerous reports in the literature of bleeding from colonic varices attributed to portal hypertension from cirrhosis or venous obstruction. However, bleeding from colonic varices located in the entire colon without demonstrable cause have only rarely been reported. PMID- 7872296 TI - Eradication of Helicobacter pylori may not reverse severe gastric dysplasia. PMID- 7872297 TI - Intermittent abdominal pain with aneurysm of the middle colic artery. PMID- 7872298 TI - Multiple submucosal ileal lipomas. PMID- 7872299 TI - Massive GI hemorrhage from an ileal duplication cyst in an adult. AB - We describe an unusual case of a 32-yr-old man who presented with massive GI hemorrhage as an initial manifestation of an ileal duplication cyst. The lesion was first revealed by visceral angiography during investigation of the bleeding source. At laparotomy, a large ileal duplication containing full-thickness gastric-type mucosa was identified. Ulceration of the ileal mucosa adjacent to the communicating orifice was found to be the source of bleeding. Duplications of the alimentary tract are rare congenital malformations. Patients usually present in infancy and childhood, although delayed complications can present in adulthood. This entity should be considered among other lesions that can cause massive GI hemorrhage not diagnosable by endoscopy. PMID- 7872300 TI - Long-term survival of peripheral intrahepatic cholangiocarcinoma with distant metastasis. PMID- 7872301 TI - Bile duct cancer associated with extramammary Paget's disease. AB - We report a case of bile duct cancer associated with anogenital Paget's disease. The patient was a 80-yr-old Japanese woman whose chief complaint was exanthema from the left vulva to the anus for the previous 4 yr. Histological examination of the skin biopsy of the vulva showed numerous Paget's cells. Resection of the lesion and the rectum were performed, and a permanent colostomy was created. More than 1 month after the operation, the patient suddenly developed obstructive jaundice. Percutaneous transhepatic cholangiography performed simultaneously with endoscopic retrograde cholangiography showed complete obstruction of the middle part of the bile duct. Bile cytology was class V. On the basis of these results, bile duct cancer associated with extramammary Paget's disease (EMPD) was diagnosed. About 5 months after the operation, the patient died of liver failure. Microscopically the tumor in the bile duct was poorly differentiated adenocarcinoma. Although EMPD has a tendency to be associated with underlying internal malignancies, this is the first reported case, to our knowledge, of bile duct cancer associated with EMPD. PMID- 7872302 TI - Portosystemic encephalopathy treated with balloon-occluded retrograde transvenous obliteration. PMID- 7872303 TI - Please, not another marker of cancer risk in Barrett's esophagus! PMID- 7872304 TI - Tense ascites in cirrhotics: a new definition? PMID- 7872305 TI - Safety of ERCP during an acute MI. PMID- 7872306 TI - Primary and acquired resistance to clarithromycin among Helicobacter pylori strains in Malaysia. PMID- 7872307 TI - Low dose clarithromycin plus omeprazole eradicates Helicobacter pylori in duodenal ulcer disease. PMID- 7872308 TI - Clinical consideration of the cytokines in inflammatory bowel disease. PMID- 7872309 TI - Spontaneous bacterial peritonitis due to Listeria monocytogenes. PMID- 7872310 TI - Portal vein thrombosis associated with bladder carcinoma. PMID- 7872311 TI - Pneumatosis cystoides intestinalis and immunosuppression. PMID- 7872312 TI - Incomplete form of Behcet's colitis in Japan: is it a distinct entity? PMID- 7872313 TI - A century of mortality in five large families with polycystic kidney disease. AB - Autosomal dominant polycystic kidney disease (ADPKD) characteristically leads to end-stage renal failure in the fifth or sixth decade of life, which in the absence of therapeutic measures will lead to premature death. To determine excess mortality relative to the general population and chromosome 16-linked ADPKD patients, we studied 348 individuals who belonged to five large ADPKD families and who had at least a 50% probability of carrying the gene; the study data derive from a time span of approximately one century. Assessment of the diagnosis of ADPKD in the present generation was based on the characteristic roentgenographic appearance of polycystic kidneys and was confirmed by DNA analysis with flanking polymorphic markers around the polycystic gene. In the previous generation, we used Mendelian reasoning after pedigree analysis to identify persons with a 50% or 100% probability of carrying the polycystic gene. During the study period (1889 to 1992), 83 deaths occurred in 10,279 person years. Mortality was increased 1.6-fold (95% confidence interval, 1.3 to 2.0) relative to the general population and was independent of the gender of the affected family member as well as the gender of the transmitting parent. The increased mortality was strongest in the 50 to 59 year age group (relative mortality, 3.2; 95% confidence interval, 2.0 to 4.8), but decreased after the 1970s, probably as a result of improvements in supportive care and, eventually, renal replacement therapy. In conclusion, the total life-span in ADPKD patients is improving, but remains low in comparison to the general population, and the gender of the transmitting parent or of the affected individual does not influence relative mortality. PMID- 7872314 TI - Tubulointerstitial lesions in human membranous glomerulonephritis: relationship to proteinuria. AB - Recent studies in experimental glomerular disease suggest that proteinuria may be involved in the pathogenesis of accompanying tubulointerstitial (TI) lesions. To investigate whether there is a relationship between proteinuria and TI damage in membranous glomerulonephritis, 78 biopsy specimens with no or mild vascular disease and 10% or less obsolete glomeruli were examined and evaluated quantitatively. Extent of TI damage was represented by the TI index (TII) obtained for each biopsy specimen by dividing the morphometrically measured area of cortical damage by the total cortical area and multiplying the result by 1,000. The TII increased with stage of glomerular disease, but only the difference between stages 3 and 1 was significant (P < 0.016). The TII showed significant individual correlation with 24-hour urinary protein (r = 0.435, P < 0.0001), serum albumin (r = -0.327, P = 0.0045), and percent of glomeruli with visceral epithelial cell protein absorption droplets (r = 0.419, P = 0.0001), but not with age, serum creatinine, or percent obsolete glomeruli. With multivariate analysis TII correlated significantly with urinary protein (r = 0.286, P = 0.0146) and percent glomeruli with visceral epithelial cell protein droplets (r = 0.304, P = 0.0058). The results are consistent with the hypothesis that proteinuria is involved in the development of TI injury in glomerular disease. PMID- 7872315 TI - Relationship between disease activity and anti-neutrophil cytoplasmic antibody concentration in long-term management of systemic vasculitis. AB - Autoantibodies directed against neutrophil cytoplasmic antigens (ANCA) are valuable in the diagnosis of primary systemic vasculitis, and immunofluorescence studies suggest that changes in ANCA concentration reflect changes in disease activity. We used enzyme-linked immunosorbent assays to examine retrospectively the relationship between ANCA concentration and disease activity in 56 patients with systemic vasculitis. We included patients with Wegener's granulomatosis, microscopic polyangiitis, idiopathic rapidly progressive glomerulonephritis, and Churg-Strauss syndrome, and examined separately the initial treatment period (mean length of follow-up, 26 months) and long-term management (mean length of follow-up, 59 months). Levels of ANCA decreased during induction therapy with prednisolone and cyclophosphamide, with or without plasma exchange. During follow up, 27 relapses were documented in 20 patients (10 with Wegener's granulomatosis, nine with microscopic polyangiitis, and one with Churg-Strauss syndrome), occurring between 4 and 183 months (mean, 62 months) after initial presentation. Patients in whom ANCA were detectable 1 year or more after treatment were at particular risk of clinical relapse. Proteinase 3-directed ANCA appeared to be associated with a higher rate of relapse (44% of patients relapsed) than myeloperoxidase-directed ANCA (13% of patients relapsed). Twenty-four of the 27 relapses occurred in the presence of detectable ANCA; in 21 of these, ANCA concentration was high or rising. The temporal relationship between changes in ANCA concentration and clinical relapse varied considerably between patients; in seven patients, ANCA remained at high levels for many months (range, 14 to 67 months) before eventual relapse. One patient showed high concentrations of ANCA over a period of 11 years without relapse. In five patients, increases in the ANCA level were not temporally associated with relapse (although four of these patients relapsed on other occasions.) We conclude that monitoring ANCA by enzyme linked immunosorbent assays is of value in the long-term management of patients with Wegener's granulomatosis, microscopic polyangiitis, idiopathic rapidly progressive glomerulonephritis, and Churg-Strauss syndrome. Increases in ANCA and persistently high levels point to the risk of relapse and indicate the need for frequent clinical review and continuing maintenance immunosuppression. However, our results suggest that ANCA assays should always be used in conjunction with other indices of disease activity and should not be the sole basis for changing therapy. PMID- 7872316 TI - Outcome of severe acute renal failure in patients with acquired immunodeficiency syndrome. AB - Among a spectrum of renal disorders encountered in patients infected with the human immunodeficiency virus (HIV), the lesion studied most often has been the glomerular disease known as HIV-associated nephropathy. Of the other coincidental renal perturbations reported, the most significant are a heterogenous group encompassing potentially reversible acute renal failure (ARF), primarily acute tubular necrosis. While HIV-associated nephropathy may frequently be seen in asymptomatic HIV-seropositive individuals, acute tubular necrosis almost always is encountered in patients with clinical acquired immunodeficiency syndrome (AIDS). We analyzed our decade's experience in the management of 146 HIV disease patients with ARF (132 AIDS patients and 14 HIV-seropositive patients) and compared it with a contemporaneous group of 306 non-HIV subjects with ARF. All patients evaluated for ARF between January 1984 and December 1993 by the Renal Division at Kings County Hospital Center, Brooklyn, NY, were reviewed. Only those patients with ARF who reached a serum creatinine concentration of 530 mumol/L or higher were included in the analysis. Ninety-one percent of 146 HIV disease patients with ARF were less than 50 years old compared with only 33% of the 306 non-HIV subjects (P < 0.001). Septicemia was directly or indirectly responsible for 75% of patients with ARF in the AIDS group and for 39% in the non-HIV subjects (P < 0.006). Urinary tract obstruction was the cause of ARF in 54 of 306 (17%) non-HIV patients compared with none in the HIV group (P < 0.00001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872317 TI - Role of systolic blood pressure in determining prognosis of hemodialyzed patients. AB - The role of blood pressure in determining the prognosis of hemodialyzed patients was examined in 195 patients who were introduced to hemodialysis. The relationship between blood pressure and survival or death was analyzed. In 46 patients who died within 3 years after the introduction of hemodialysis (nonsurvivors), the age was higher (61 +/- 2 years v 50 +/- 1 years), the occurrence of diabetic nephropathy was higher, and the systolic pressure was higher in both the introduction (178 +/- 4 mm Hg v 167 +/- 2 mm Hg) and maintenance (165 +/- 4 mm Hg v 147 +/- 2 mm Hg) phases than in 132 patients who survived more than 3 years (survivors). On the other hand, there were no significant differences in diastolic pressure during either phase between the two groups of patients. When diabetic nephropathy was excluded, only systolic pressure during the maintenance phase was higher in the nonsurvivors than in the survivors. Therefore, based on systolic pressure during the maintenance phase, patients were divided into two groups, the HT group (> or = 160 mm Hg) and the NT group (< 160 mm Hg), and cumulative survival rates were compared. Whether all patients, only those patients with diabetic nephropathy, or only those patients without diabetic nephropathy were examined, the survival rate was higher in the NT group than in the HT group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872318 TI - Optimal dialysis improves uremic pruritus. AB - The authors analyzed data on 59 hemodialyzed patients who did not have significant disorders of calcium and phosphate metabolism and found that more than 60% suffered from disabling pruritus possibly related to chronic uremia. Both biochemical correlates of the prevalence of pruritus and dialysis efficacy calculated by urea kinetics were investigated. Significantly higher values of blood urea nitrogen and plasma beta 2-microglobulin just before the dialysis session were observed in pruritic patients with lower dialysis efficacy estimated by Kt/V urea and normalized protein catabolic rate (nPCR). After 3 months without changing the dialysis prescriptions, 16 patients with a mean Kt/V urea and a normalized protein catabolic rate (nPCR) of 1.28 and 1.22 g/kg/d, respectively, experienced significant reductions in the degree of pruritus estimated by the pruritic score, from 12.6 +/- 5.1 to 6.3 +/- 3.2. Twenty-two patients with a mean Kt/V urea and an nPCR of 1.09 and 1.01, respectively, continued to have severe pruritus (score: 12.3 +/- 4.7 to 12.7 +/- 6.4). In 9 of 22 patients with prolonged severe pruritus, dialysis efficacy was heightened with an increase in dialyzer membrane area of more than 0.3 m2. Seven of nine patients with increased dialysis prescriptions had significant reductions of the mean pruritic score, from 12.6 +/- 4.8 to 6.3 +/- 2.4, which inversely related to the significant increase of Kt/V urea from 1.05 +/- 0.25 to 1.24 +/- 0.33; among patients whose dialysis prescriptions were not changed, only one had a significant reduction in score. The authors concluded that higher dialysis efficacy with good nutritional state reduces the prevalence and degree of pruritus in hemodialyzed patients. PMID- 7872319 TI - The pharmacokinetics of aminoguanidine in end-stage renal disease patients on hemodialysis. AB - Aminoguanidine is an investigational agent that may slow or prevent many diabetes related complications. Since the elimination of aminoguanidine is dependent on renal function, its pharmacokinetics was investigated in eight chronic renal failure patients maintained on hemodialysis. Each patient received 300 mg of aminoguanidine hydrochloride during both an interdialytic and an intradialytic period. During the interdialytic period, the maximum aminoguanidine concentration (Cmax) and time to reach Cmax was 4.5 micrograms/mL and 1.5 hours, respectively. The terminal elimination half-life in these patients was prolonged (37.9 hours). The renal clearance was 2.1 mL/min. Only 8.7% of the administered dose was recovered unchanged in the urine, which is markedly reduced from what is recovered in urine in subjects with normal renal function. There was a positive correlation between the renal clearance of aminoguanidine and the patients' residual renal function (P < 0.05). During hemodialysis, the half-life of aminoguanidine was shortened to 3.9 hours. The hemodialysis clearance of aminoguanidine was 203.6 mL/min. After cessation of hemodialysis, a significant rebound in plasma aminoguanidine concentrations (mean, 39%) was observed. Thus, the dose of aminoguanidine hydrochloride will need to be significantly reduced in patients with end-stage renal disease. Given the interdialytic and intradialytic pharmacokinetics of aminoguanidine, three times weekly dosing after each hemodialysis session is suggested. PMID- 7872320 TI - The utility of zinc protoporphyrin for predicting the need for intravenous iron therapy in hemodialysis patients. AB - The optimal method for diagnosing iron deficiency in end-stage renal disease is an area of controversy. This study compared the use of zinc protoporphyrin (ZPP) with the use of conventional tests for determination of iron deficiency when evaluating the need for intravenous iron therapy in hemodialysis patients maintained on erythropoietin (EPO). A baseline survey was performed in all hemodialysis patients at the Baumritter Kidney Center (Bronx, NY), measuring ZPP, ferritin, transferrin saturation (TSAT), mean corpuscular volume, and hematocrit. Patients with ZPP > or = 90 mumol/mol heme or ferritin less than 100 ng/mL were considered likely to be iron deficient and were treated with 1,000 mg of intravenous iron dextran over 10 hemodialysis treatments. The positive predictive values of ferritin and ZPP for predicting a response to intravenous iron dextran were similar (73% v 83%, respectively; two-tailed, P = 0.48). To determine the sensitivity and specificity of the tests, patients were divided into two groups at the end of the study period: those in whom iron therapy was required (n = 23) (patients treated with intravenous iron dextran who had a 5% increase in hematocrit or a decrease in erythropoietin dose of > or = 2,000 U/treatment) and those in whom iron therapy was not required (n = 24) (patients either treated with intravenous iron dextran without a response [n = 9] or patients whose initial ZPP and ferritin levels were not suggestive of iron deficiency and who maintained a stable hematocrit and erythropoietin dose during the study period [n = 15]).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872321 TI - Efficacy of oral iron therapy in patients receiving recombinant human erythropoietin. AB - Iron supplementation is required by most dialysis patients receiving recombinant human erythropoietin. The efficacy of oral iron is variable in these patients, and many require the use of intravenous iron dextran to maintain adequate iron levels, defined as transferrin saturation greater than 20%, serum ferritin greater than 100 ng/mL, and serum iron greater than 80 micrograms/dL. To determine the efficacy of different oral iron preparations in maintenance of iron status, we prospectively studied 46 recombinant human erythropoietin-treated patients and randomized them to receive different oral iron preparations. These four preparations included Chromagen (ferrous fumarate; Savage Laboratories, Melville, NY), Feosol (ferrous sulfate; SmithKline Beecham, Inc, Pittsburgh, PA), Niferex (polysaccharide; Central Pharmaceuticals, Inc, Seymour, IN), or Tabron (ferrous fumarate; Parke-Davis, Morris Plains, NJ). All patients were prescribed approximately 200 mg of elemental iron daily of their assigned iron preparation with at least 100 mg ascorbic acid daily for 6 months. At baseline and bimonthly during the study, serum iron, transferrin saturation, ferritin, hematocrit, and recombinant human erythropoietin dose were monitored; in addition, compliance and side effects were recorded by patient interview. All patients were able to maintain target hematocrit during the 6 months of study. However, there were differences in the trends of serum iron, percent transferrin saturation, and ferritin when considered singly or in combination between the four groups of iron medications. The percent of laboratory values measured over the study period in each group that met the criteria of transferrin saturation more than 20% was greatest in the Tabron group (58%), followed by the Feosol (47%), Chromagen (33%), and Niferex (31%) groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872322 TI - Effect of treatment of hemodialysis patients with nifedipine on metabolism and function of polymorphonuclear leukocytes. AB - Both animals and patients with chronic renal failure have impaired phagocytosis, which is most likely due to elevated basal levels of cytosolic calcium ([Ca2+]i) and reduced adenosine triphosphate (ATP) content of their polymorphonuclear leukocytes (PMNLs). In animals with chronic renal failure, these derangements are prevented or reversed by their treatment with a calcium channel blocker. This observation may have important clinical implications if these drugs exert a similar effect in humans with chronic renal failure. We examined the basal levels [Ca2+]i, ATP content, and phagocytosis in PMNLs from 11 normal subjects, 18 hemodialysis patients (seven of whom had diabetes mellitus), and 18 hemodialysis patients treated with nifedipine (eight of whom had diabetes mellitus). The basal levels of the [Ca2+]i content of the PMNLs in hemodialysis patients without nifedipine therapy were significantly (P < 0.01) elevated (nondiabetic patients, 77 +/- 3.2 nmol/L; diabetic patients, 75 +/- 1.9 nmol/L) compared with normal values (42 +/- 0.9 nmol/L). Treatment with nifedipine was associated with the return of [Ca2+]i toward normal values in both the nondiabetic (51 +/- 4.5 nmol/L) and diabetic (54 +/- 2.5 nmol/L) hemodialysis patients. The ATP content of PMNLs from hemodialysis patient was significantly (P < 0.01) reduced compared with normal, and nifedipine therapy restored the ATP content to normal values. Phagocytosis was significantly (P < 0.01) impaired in hemodialysis patients (nondiabetic patients, 78 +/- 4.0 micrograms oil/10(7) PMNLs/min; diabetic patients, 77 +/- 4.8 micrograms oil/10(7) PMNLs/min). Nifedipine therapy returned the impaired phagocytosis toward normal (nondiabetic patients, 133 +/- 2.5 micrograms oil/10(7) PMNLs/min; diabetic patients, 129 +/- 6.4 micrograms oil/10(7) PMNLs/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872323 TI - Influence of dialysis modality on plasma and tissue concentrations of pentosidine in patients with end-stage renal disease. AB - Plasma and tissue concentrations of pentose-derived glycation end-products ("pentosidine") are elevated in diabetic patients with normal renal function and in both diabetic and nondiabetic patients with end-stage renal disease. To determine the influence of dialysis modality and other clinical variables on the accumulation of pentosidine, we used high-performance liquid chromatography to measure this advanced glycation end-product in plasma, skin, and peritoneal samples obtained from 65 hemodialysis and 45 peritoneal dialysis patients. Plasma pentosidine levels were significantly lower in peritoneal dialysis patients. Concentrations of pentosidine in skin were similar in the two groups. In contrast, peritoneal concentrations of pentosidine were significantly higher in the patients maintained on peritoneal dialysis. Our results demonstrate that dialysis modality influences the plasma and tissue distribution of pentosidine. Compared with hemodialysis, peritoneal dialysis is associated with lower levels of this glycation end-product in plasma, but with higher levels in the peritoneum. The mechanisms accounting for lower circulating levels of pentosidine in peritoneal dialysis patients remain to be determined. Higher levels in peritoneal tissues may reflect chronic exposure to the high concentrations of glucose in peritoneal dialysate. PMID- 7872325 TI - Outcome of polymicrobial peritonitis in continuous ambulatory peritoneal dialysis patients. AB - Polymicrobial peritonitis is a relatively uncommon, but potentially serious complication that develops in continuous ambulatory peritoneal dialysis (CAPD) patients. Its cause and optimal management remain controversial. The authors reviewed the frequency and natural history of polymicrobial peritonitis in 432 CAPD patients. Of 1,405 episodes of peritonitis, 80 were polymicrobial (6%). Patients with polymicrobial peritonitis were similar to all CAPD patients in age, gender, race, and underlying renal disease. Diabetes mellitus, human immunodeficiency virus (HIV) status, and clinically apparent gastrointestinal disease did not predisposes patients to polymicrobial peritonitis. Thirty days after the polymicrobial peritonitis, 64 patients remained on CAPD (80%), and at 180 days 48 patients continued CAPD. Prior exit-site infections were present in 12 patients (14%) with polymicrobial peritonitis. Only 22% of patients required catheter removal to treat the infection. We conclude that polymicrobial peritonitis accounts for 6% of the total episodes of peritonitis; diabetes, HIV infection, and underlying gastrointestinal disease are not more prevalent in patients with multiorganism infections. Most patients continue CAPD therapy at 30 and 180 days after the episode of polymicrobial peritonitis. PMID- 7872324 TI - Low dialysate calcium in continuous ambulatory peritoneal dialysis: a randomized controlled multicenter trial. The Peritoneal Dialysis Multicenter Study Group. AB - Hypercalcemia is a common complication in continuous ambulatory peritoneal dialysis (CAPD) patients treated with calcium-containing phosphate binders and using the standard dialysate calcium concentration of 3.5 mEq/L (SCa). Lowering the dialysate calcium was proposed to overcome this problem. The current randomized controlled multicenter study was designed to investigate efficiency and safety of a low calcium dialysate (2.00 mEq/L; LCa) compared with SCa (3.5 mEq/L) in CAPD patients. After an 8-week run-in period, 103 stable CAPD patients, 68 men, 35 women, aged 54.5 years (range, 20 to 77)) were randomly allotted to treatment with either LCa or SCa. All patients received calcium carbonate as oral phosphate binder to achieve serum phosphate levels < 6.2 mg/dL. If persistent hypercalcemia arose, CaCO3 was replaced by Al(OH)3 until normocalcemia was achieved. All patients received 0.25 microgram calcitriol/d. Parameters monitored included total and ionized serum calcium, serum phosphate, phosphate binder intake, incidence of hypercalcemia, serum aluminium, intact parathyroid hormone (1,84PTH), osteocalcin, alkaline phosphatase, bone mineral density and hand skeletal x-ray. Primary end points were (a) number of hypercalcemic episodes, (b) tolerated doses of calcium-containing phosphate binders, and (c) 1,84PTH. After 6 months of therapy, total and ionized calcium were lower in LCa patients (total Ca:9.6 v 10.08 mEq/L, P = 0.005; iCa: 4.76 v 5.15 mg/dL; P = 0.013). In the LCa group, significantly fewer episodes of hypercalcemia were recorded (total S calcium > 10.8 mg/dL: LCa 24 v SCa 86 episodes; P < 0.005). Use of LCa permitted the administration of more CaCO3 (mean daily tablet number: LCa, 5.9 v SCa, 4.2; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872326 TI - Pregnancy and kidney transplantation: experience in a developing country. AB - Between January 1968 and December 1992, 136 kidney transplants were performed in the University Hospital of Ribeirao Preto, with women of childbearing age (14 to 40 years) as receptors. From this population, 19 patients became pregnant at least once after transplantation, and 2 were transplanted inadvertently during the first trimester of their pregnancies. There was a total of 25 pregnancies and 27 offspring. The mean age at the time of conception was 28.6 years (23 to 41 years), with a mean interval of 3.5 years from transplant to conception (< 1 to 16 years). All patients continued their immunosuppressive regimens during the entire pregnancy, but only 5 of 25 were taking cyclosporine. There were two miscarriages (8%) and two therapeutic abortions (8%); of those that passed the 20th week of pregnancy, the mean gestation time at delivery was 35 weeks (range, 28 to 38 weeks) with an incidence of prematurity (gestation < 37 weeks) of 67%, and their offspring weighed from 670 to 3,100 g (mean, 2,236 g), presenting a very high incidence of low birthweight (64%). There was one stillborn and one neonatal death. The most common complications that occurred during pregnancy were infections (especially urinary tract and vaginal mycotic infections) followed by hypertension. The obstetric complications were distributed as follows: premature rupture of membranes in 27%, fetal distress in 24%, preterm labor in 24%, and oligohydramnios in 10%. Lower segment cesarean section was necessary in 16 of 21 cases (76%), and all were for obstetric reasons. One patient died during the puerperium because of sepsis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872327 TI - Cyst fluid from a murine model of polycystic kidney disease stimulates fluid secretion, cyclic adenosine monophosphate accumulation, and cell proliferation by Madin-Darby canine kidney cells in vitro. AB - Cyst fluids from subjects with autosomal dominant polycystic kidney disease (ADPKD) cause polarized monolayers of MDCK cells to secrete fluid toward the apical compartment in vitro. To determine the extent to which secretagogue accumulation may be a general feature of polycystic diseases, cyst fluid from mice with a slowly progressive form of hereditary PKD (DBA/2FG-pcy/pcy) was added to polarized MDCK monolayers. Basolateral application of cyst fluids (diluted with culture medium to 15% final concentration) from 13 different animals 16 to 35 weeks old increased the fluid secretion rate from a baseline of 0.023 +/- 0.003 to 0.111 +/- 0.017 microL/cm2/h (P < 0.005). There was a direct relation between the concentration of cyst fluid and the rate of net fluid secretion. The secretory activity of cyst fluid was not altered by pronase treatment or boiling. Cyst fluid (10%) added to the basolateral surfaces of polarized MDCK monolayers for 24 hours increased cell cyclic adenosine monophosphate (AMP) levels from a baseline of 6.3 +/- 0.2 to 17.3 +/- 0.3 pmoles/monolayer (n = 3, P < 0.05). The capacity of cyst fluid to increase cyclic AMP levels was not changed by pronase treatment or boiling. There was a direct relation between the level of cellular cyclic AMP and the rate of transepithelial fluid secretion caused by cyst fluid. Cyst fluid increased thymidine incorporation by Madin-Darby canine kidney (MDCK) cells to an extent equal to that caused by epidermal growth factor and caused MDCK cells to form cysts in collagen matricies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872328 TI - Tubulointerstitial lesions in young Zucker rats. AB - Zucker (Z) rats spontaneously develop proteinuria and focal glomerulosclerosis (FGS), but little is known about tubulointerstitial (TI) changes in the early stages of their disease. Thirteen male Z rats (9 obese, 4 lean) were examined at 75 (n = 6) and 120 (n = 7) days of age. Twenty-four-hour urinary protein excretion (UPr), percent of glomeruli with FGS, proportion of cortex and outer stripe occupied by vimentin (V)-positive (+) tubules (a marker of tubular damage) and the number of OX4+ (Ia+), OX42+(monocyte/macrophage), OX19+(pan T cell), OX8+(T cytotoxic cell), and OX22+(B cell) cells in both normal areas and around V+ tubules were assessed at each age. Mean UPr was 34.2 +/- 18.5 mg/day at 75 days and 183.6 +/- 129.9 mg/day at 120 days. FGS was only observed in 1% to 3% of glomeruli in five 120-day-old obese rats. All rats showed varying degrees of focal TI injury histologically. V+ tubules were observed in 12 rats, and the proportion of cortex and outer stripe occupied by V+ tubules varied from 0.1% to 7.7%. The extent of TI damage was greater at 120 days (3.7% +/- 2.9%) than at 75 days (0.5% +/- 0.5%). There was a 2- to 12-fold increase in the number of OX4+, OX42+, OX19+, and OX8+ cells in areas around V+ tubules, with OX4+ and OX42+ cells predominating.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872329 TI - Captopril and aspirin in treatment of renal microangiopathy in primary antiphospholipid syndrome. AB - Treatment of antiphospholipid syndrome (APS) is controversial. We report a case of renal microangiopathy in a 40-year-old woman with APS. The nephropathy was isolated without signs of disseminated thrombotic microangiopathy or progressive systemic sclerosis. Similarities with sclerodermatous kidney and an increase in plasma renin activity led us to initiate treatment with aspirin and captopril, with excellent control of the renal syndrome. We believe this therapeutic regimen may be an effective means of treating the renal microangiopathy of APS. PMID- 7872330 TI - An unusual renal complication in a patient with osteogenesis imperfecta. AB - Osteogenesis imperfecta (OI) is a common 'rare' disorder with a reported incidence of 1/15,000 to 1/20,000 in newborns. Skeletal abnormalities in this condition are so striking that its equally important and diverse extraskeletal manifestations frequently remain unnoticed. Sensorineural deafness, blue sclerae, myopia, easy bruisability, dental anomalies, and floppy mitral valves are some of its more frequently reported extraskeletal features. Other less common features include pulmonary hypoplasia, joint contractures, hydrocephalus, and osteogenic sarcoma. Our patient, a 16-year-old boy, developed a previously unreported complication: chronic renal failure, which on subsequent evaluation was attributed to obstructive uropathy secondary to bony pelvic outlet deformities. PMID- 7872331 TI - Cutaneous oxalate deposition in a hemodialysis patient. AB - We describe calcium oxalate and amyloid arthropathy with cutaneous calcinosis without vitamin C supplement. A 34-year-old woman developed glomerulonephritis requiring chronic hemodialysis. Seven years after beginning hemodialysis, multiple crystal deposits appeared in her skin; she also presented with arthralgia and gait disturbance. A skin biopsy was performed, which disclosed calcium oxalate deposition. In addition, a right femoral neck prosthetic replacement was performed. Pathologic examination of the hip synovia revealed diffuse calcium oxalate, amyloid, and iron deposition. Calcium oxalate and amyloid arthropathy with synovial hemosiderosis was diagnosed, and therapy with desferal and high-flux membrane dialysis was started. Clinical improvement occurred after 6 months. PMID- 7872332 TI - Calciphylaxis presenting with calf pain and plaques in four continuous ambulatory peritoneal dialysis patients and in one predialysis patient. AB - Calciphylaxis is a rare disease associated with hemodialysis or transplantation, high parathyroid hormone values, and increased serum calcium x phosphate (Ca x P) product. Only four patients on continuous ambulatory peritoneal dialysis have been reported with this condition. We report five cases presenting within a 2 year period with severe calf pain and tenderness with extensive nonulcerating large, hard, and tender subcutaneous plaques in the calves. Calcium deposition was confirmed radiologically and by bone scanning. Four patients were on continuous ambulatory peritoneal dialysis, and the other was not yet on dialysis. High serum Ca x P product was found in three of these patients at onset of the condition. Two patients had normal parathyroid hormone levels at onset. Calcium salts and/or calcitriol had been taken prior to onset in three patients. When presenting in this fashion, the diagnosis can be easily made by the uniqueness of the physical findings in the legs. Our observation suggests that the condition should no longer be considered rare and is not confined to hemodialysis patients. Furthermore, it can occur in predialysis patients. PMID- 7872333 TI - Acute cyclosporine A nephrotoxicity in a renal allograft recipient with hypothyroidism. AB - Cyclosporine A (CsA) is an important immunosuppressant in kidney transplantation. Acute CsA nephrotoxicity secondary to high drug levels is a well-recognized complication in the immediate posttransplant period. Cyclosporine A is metabolized in the body by the hepatic cytochrome P-450 enzyme system. We present a case of a hypothyroid patient who developed toxic blood CsA levels and acute nephrotoxicity with standard doses of CsA. A reduction of CsA levels led to an improvement of allograft function. Correction of the hypothyroid state resulted in the normalization of CsA requirements, but overcorrection led to an increased requirement of CsA. Thyroid dysfunction should be considered as an interacting factor in the metabolism of CsA. PMID- 7872334 TI - Sensing of extracellular Ca2+ by parathyroid and kidney cells: cloning and characterization of an extracellular Ca(2+)-sensing receptor. AB - The ability of the parathyroid cell to sense minute fluctuations in the extracellular ionized calcium concentration (Ca2+ o) is essential for maintaining mineral ion homeostasis. However, the mechanism(s) through which the parathyroid cell and other cells recognize and respond to changes in Ca2+ o has remained unclear. We recently isolated a cDNA encoding a Ca2+ o-sensing receptor from bovine parathyroid using expression cloning in Xenopus laevis oocytes. The receptor shows pharmacologic properties that are almost identical to those of the receptor on the parathyroid cell and, like the latter, stimulates phospholipase C in a G-protein-dependent manner. The amino acid sequence of the cloned receptor deduced from this cDNA predicts a protein with a molecular mass of 121 kd, which has three principal structural domains. The first is a 613 amino acid, putatively extracellular amino terminus which has several regions rich in acidic amino acids that may potentially be involved in binding Ca2+ and other polycationic agonists. The second comprises seven membrane-spanning segments that are characteristic of the superfamily of G-protein-coupled receptors, and the third is a 222 amino acid cytoplasmic tail. Transcripts for this Ca2+ o-sensing receptor are present in the parathyroid as well as in the kidney, thyroid, and brain. We next investigated the hypercalcemic disorders, familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism, as possible examples of inherited abnormalities in this Ca2+ o-sensing receptor, since both disorders show abnormal Ca2+ o-sensing and/or handling in the kidney and parathyroid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872335 TI - What constitutes an optimal education for the future academic subspecialist: integration of science and medicine? PMID- 7872336 TI - Is it time to redefine the management of febrile neutropenia in cancer patients? PMID- 7872337 TI - Feasibility of outpatient management of fever in cancer patients with low-risk neutropenia: results of a prospective randomized trial. AB - PURPOSE: We recently demonstrated the efficacy of single-agent oral ofloxacin in the management of hospitalized neutropenic febrile patients. Ofloxacin was particularly effective in patients with short duration of neutropenia and fever of undetermined origin. These results prompted us to study the feasibility of outpatient management of neutropenic febrile patients who are otherwise at low risk of morbidity and mortality. PATIENTS AND METHODS: This multi-institutional, prospective, randomized trial included 182 low-risk neutropenic febrile episodes. After an initial work-up for fever, patients were randomized to receive oral ofloxacin 400 mg immediately and twice daily thereafter in the hospital or as outpatients. Close monitoring and follow-up were carried out in all patients. Those who failed to respond and remained febrile were given parenteral antibiotics. Nonresponding outpatients were admitted to the hospital for parenteral therapy. RESULTS: One hundred sixty-nine episodes were evaluable. The hospital and outpatient treatment groups had comparable clinical characteristics. Pyrexias of undetermined origin (PUO) comprised 69% of episodes managed in hospital and 73% of episodes treated outside. The success rate with PUO was similar with inpatient and outpatient management. Patients with clinical and microbiologic infections fared less well than those with PUO. Overall, 78% of inpatient and 77% of outpatient fevers resolved with no modification of the initial treatment. Twenty-one percent of patients originally assigned to outside management required hospitalization. Mortality was 2% among inpatients and 4% among outpatients. One early death in a nonhospitalized patient underscores the need for close monitoring and surveillance in these cases. CONCLUSIONS: Outpatient management of low-risk neutropenic febrile patients with ofloxacin is as effective as inpatient management with the same agent. This approach should be limited to the subset of patients with low-risk factors who are not otherwise on quinolone prophylaxis. PMID- 7872338 TI - Identifying problem drinkers: lack of sensitivity of the two-question drinking test. AB - BACKGROUND AND OBJECTIVE: The two-question drinking test ("Have you ever had a drinking problem?" and "When was your last drink?") is frequently cited as an accurate method of screening for alcoholism, yet its performance has never been validated. This study evaluated its utility among patients in two primary care settings. PATIENTS AND METHODS: The two-question drinking test was compared to the Michigan Alcohol Screening Test (MAST) as the standard criterion for the diagnosis of alcoholism. The subjects were 334 nonpregnant English-speaking patients over the age of 18 seen in two university outpatient teaching clinics. RESULTS: The overall prevalence of alcoholism based on a MAST score > or = 5 was 18%. The sensitivity of the two-question test was 53% and its specificity 93%. The question "When was your last drink?" added little to the question "Have you ever had a drinking problem?" The latter question alone had a sensitivity of 50% and a specificity of 97%. CONCLUSIONS: The two-question test is not sensitive enough to be used to screen for alcohol abuse among outpatients. However, because of the low false positive rate, a positive response to the question "Have you ever had a drinking problem?" may help identify alcoholic patients. PMID- 7872339 TI - Frequency and reactivation of nongenital lesions among patients with genital herpes simplex virus. AB - OBJECTIVE: To determine the frequency, recurrence patterns, and host factors associated with nongenital herpes simplex virus lesions. PATIENTS AND METHODS: In this cohort study at a referral clinic, 457 patients with first episodes of genital herpes were prospectively observed to evaluate the anatomic sites of herpetic lesions at the first and subsequent visits. Of these patients, 73 had primary genital herpes simplex virus (HSV) type 1, 326 had primary first episode genital HSV-2, and 58 had HSV-1 infection prior to acquisition of genital HSV-2. The median follow-up was 63 weeks. RESULTS: Nongenital lesions at the time of acquisition of genital herpes were observed in 25%, 9%, and 2% of patients with primary HSV-1, primary HSV-2, and nonprimary HSV-2, respectively. Half of the patients with concurrent genital and nongenital lesions subsequently had recurrences at a nongenital site. Twenty patients (6.5%) whose primary genital HSV-2 infection involved only the genitalia subsequently developed nongenital recurrences, primarily on the buttocks (12) and legs (4). Nongenital recurrences, especially buttock recurrences, tended to be less frequent but of longer duration than genital recurrences. CONCLUSIONS: Overall, 21% of patients with primary genital herpes will have or will subsequently develop a nongenital recurrence. Among patients with HSV-1, nongenital lesions tended to occur more often on the hand and face, whereas HSV-2 lesions appeared more often on the buttocks. Buttock lesions due to HSV recur less frequently but last longer than genital lesions. PMID- 7872340 TI - Acute pancreatitis in HIV-seropositive patients: a case control study of 44 patients. AB - PURPOSE: To analyze whether pancreatitis presents differently in HIV-seropositive patients compared to the general population, and to evaluate the accuracy of classic predictors of pancreatitis severity in patients with HIV infection. METHODS: A multiyear, multicenter, retrospective study of 44 consecutive patients with acute pancreatitis and HIV and 44 consecutive control patients with acute pancreatitis without HIV. RESULTS: Of 939 hospitalized patients with HIV, 44 (4.7%) had acute pancreatitis, 27 of whom had AIDS. Pancreatitis presented with similar clinical findings in HIV patients and controls except that HIV patients had greater anemia, hypoalbuminemia, and leukopenia (Student's t-test P < 0.0001, < 0.0002, < 0.0001, respectively), and a higher incidence of fever, diarrhea, and hepatomegaly. These differences probably stem from HIV-related immunosuppression and malnourishment rather than pancreatitis. Patients with HIV had a higher frequency of medication-associated pancreatitis due to pancreatoxic medications used in HIV patients (18 versus 2 cases; odds ratio [OR] 14.54; Student's t-test P < 0.0001). They had a lower frequency of gallstone pancreatitis (2 versus 22 cases; OR 0.05; P < 0.0001). Patients with HIV had a higher frequency of a severe hospital course, defined as prolonged hospitalization or death in hospital (22 versus 12 cases; chi-square P < 0.05). The presence of AIDS or leukopenia in patients with HIV was strongly associated with a severe hospital course. The Ranson and modified Glasgow scales were poor predictors of disease severity in HIV patients (eg, Ranson scale sensitivity 41%; positive predictive value 53%; negative predictive value 52%). These scales' lack of markers of immunosuppression impeded their performance. The APACHE II scale, which contains markers of immunosuppression, was a moderately robust predictor of disease severity in HIV patients (sensitivity 73%; specificity 68%; positive predictive value 70%; negative predictive value 71%). All three scales predicted the disease severity in control patients well. CONCLUSIONS: Pancreatitis presents similarly in HIV patients as in the general population with the following significant differences: a high frequency of medication-associated pancreatitis, a low frequency of gallstone pancreatitis, a high frequency of HIV-related causes (most commonly from HIV-related drugs), additional symptoms and signs due to underlying immunosuppression, and a more severe hospital course. The APACHE II system can be used to predict whether a patient with HIV and pancreatitis is at risk for prolonged hospitalization or death in hospital. PMID- 7872342 TI - Brain natriuretic peptide as a marker for hypertensive left ventricular hypertrophy: changes during 1-year antihypertensive therapy with angiotensin converting enzyme inhibitor. AB - PURPOSE: Secretion of brain natriuretic peptide (BNP), a cardiac hormone, is accelerated via hypertrophied ventricles in experimental hypertension. The present study examined whether regression of left ventricular (LV) hypertrophy by long-term treatment with an angiotensin-converting enzyme inhibitor (ACEI) affects plasma BNP concentration in patients with essential hypertension. PATIENTS AND METHODS: Thirty-one hypertensive patients with LV hypertrophy were treated with ACEI (16 with enalapril; 15 with lisinopril) for 1 year. Serial changes were recorded in LV mass index, LV systolic function, and plasma concentrations of BNP and atrial natriuretic peptide (ANP). RESULTS: ACEI therapy significantly reduced LV mass index at 6 months, and more so at 1 year. Septal and posterior wall thicknesses were also reduced. Plasma BNP and ANP were markedly elevated at study entry, but only BNP levels correlated with LV mass index. Both peptide levels declined after 6 months, and this decline was enhanced at 1 year. There was a close relation between BNP decline and LV mass index reduction overall and with enalapril and lisinopril separately. Changes in ANP and in LV mass index were not related. CONCLUSION: Long-term ACEI therapy can reduce elevated plasma BNP. In this study, changes in BNP reflected the magnitude of regression of LVH. Plasma BNP may be a useful marker for LVH during antihypertensive therapy in patients with essential hypertension and LVH. PMID- 7872341 TI - Fluconazole in the treatment of chronic pulmonary and nonmeningeal disseminated coccidioidomycosis. NIAID Mycoses Study Group. AB - PURPOSE: To determine the efficacy and safety of fluconazole as treatment for coccidioidomycosis. PATIENTS AND METHODS: This was a multicenter, open-label, single-arm study. Of 78 patients enrolled, 22 had soft-tissue, 42 had chronic pulmonary, and 14 had skeletal coccidioidomycosis. Forty-nine had at least one concomitant disease, 7 of whom had HIV infection. Patients were given oral fluconazole 200 mg/d. Nonresponders were increased to 400 mg/d. Treatment courses were long: a mean of 323 +/- 230 days at 200 mg and 433 +/- 178 days at 400 mg. Predefined assessment of disease-related abnormalities was performed at the time of enrollment and repeated at least every 4 months. A satisfactory response was defined as any reduction of baseline abnormality by month 4 and at least 51% reduction by month 8. RESULTS: Among 75 evaluable patients, a satisfactory response was observed in 12 (86%) of the 14 patients with skeletal, 22 (55%) of the 40 patients with chronic pulmonary, and 16 (76%) of the 21 patients with soft tissue disease. Five patients (7%) required modification of treatment due to toxicity. Forty-one patients who responded were followed off drug. Fifteen (37%) of them experienced reactivation of infection. CONCLUSION: Fluconazole 200 or 400 mg/d is well tolerated and a moderately effective treatment for chronic pulmonary or nonmeningeal disseminated coccidioidomycosis. The relapse rate following therapy is high. Treatment trials with higher doses appear warranted. The relative efficacy of fluconazole versus other azoles or amphotericin B remains unknown. PMID- 7872343 TI - Adrenal insufficiency occurring during septic shock: incidence, outcome, and relationship to peripheral cytokine levels. AB - PURPOSE: In patients with septic shock, to (1) determine the incidence of adrenal insufficiency (AI), (2) observe the effects of glucocorticoid therapy on outcome in those with impaired adrenal function, and (3) investigate a possible correlation between adrenal function and peripheral cytokine levels. PATIENTS AND METHODS: Twenty-one patients admitted to the medical and surgical intensive care unit with septic shock and 11 healthy volunteers were studied. Cortisol, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels were measured before and after infusion of low (1 microgram) and standard doses (250 micrograms) of adrenocorticotropic hormone (ACTH) within 24 hours of the diagnosis of septic shock. Patients with subnormal adrenal responses to ACTH were treated with stress doses of steroids. Hormone, cytokine, and survival data in patients with normal response were compared to those with subnormal adrenal function. RESULTS: Five patients (23.8%) exhibited AI by ACTH stimulation testing. Three of them received steroid supplementation with rapid improvement in hemodynamic parameters. Autopsies of 2 patients with AI revealed intact adrenal cortices. Sixteen patients had adequate adrenal responses (AAR) to the standard dose ACTH infusion. TNF-alpha levels were inversely correlated with mean arterial pressure (MAP) (r = -.52, P = 0.038) in AAR but not AI. There was no difference in mean peripheral TNF-alpha levels between AAR and AI. There was no correlation between TNF-alpha levels and mortality or adrenal function in those with septic shock. A trend toward lower IL-6 levels in AI suggests a link between reduced IL 6 levels and understimulation of the pituitary-adrenal axis in this group. Mortality in patients with AI was 80% at 4 weeks as compared with 43.8% in the group with normal adrenal response. CONCLUSIONS: Adrenal hyporesponsiveness is a feature of septic shock in some patients. Its etiology is probably complex. Steroid supplementation appeared to improve short-term survival when AI occurred, although these patients' overall mortality was worse than that of patients with septic shock and AAR. The standard-dose (250 micrograms) rapid ACTH infusion test was adequate for detecting AI. Adrenal insufficiency should be suspected in patients with septic shock who do not respond to conventional treatment. Performing the ACTH infusion test and initiating a trial of stress doses of glucocorticoids pending the results is a reasonable strategy in this situation. PMID- 7872345 TI - Diagnostic dilemmas presented by patients with anxiety and depression. AB - Although anxiety and depression are among the most common symptoms of persons seen in medical practice, a number of dilemmas still exist in the identification and management of these disorders. The objectives of this paper are to review the prevalence and identification of anxiety, depression, and mixed anxiety depression in medical practice; to review issues involving the medical evaluation of these disorders; to clarify the relevance of psychosocial issues to choice of treatment; and to review issues involving medication treatment choices. PMID- 7872344 TI - Predicting mortality of patients hospitalized for acutely exacerbated chronic obstructive pulmonary disease. AB - PURPOSE: To identify factors affecting the short-term prognosis of patients with acutely exacerbated chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: The 590 patients having COPD as primary disease who were hospitalized in the pneumology unit of a university hospital from 1981 to 1990 were studied. A standardized protocol for the treatment of acutely exacerbated COPD was adopted for all the patients. The patient records were retrospectively analyzed by two observers, and 23 clinical and laboratory variables defining the patient status on admission were collected. Age and arterial gas data were also taken into account, and the outcome mortality was recorded. Interobserver reproducibility was tested by computing the kappa coefficient and Spearman's rho for dichotomous and continuous variables, respectively. The relationship of clinical and laboratory factors to the outcome was assessed first by univariate analysis and then by a logistic regression analysis assessing the independent predictive role of variables previously shown to be univariately correlated with mortality. RESULTS: The mortality rate was 14.4%. The logistic regression analysis identified four independent predictors of death: age (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.04 to 1.11), alveolar-arterial oxygen gradient greater than 41 mm Hg (OR 2.33; 95% CI 1.39 to 3.90), ventricular arrhythmias (OR 1.91; 95% CI 1.10 to 3.31), and atrial fibrillation (OR 2.27; 95% CI 1.14 to 4.51). CONCLUSIONS: Patients with acutely exacerbated COPD having a high risk of death can be identified at the time of admission. Variables reflecting heart dysfunction are important determinants of this risk. Among pulmonary function data, only alveolar-arterial oxygen gradient contributes to the predictive model. PMID- 7872346 TI - Guidelines for interpretation of some common indicators of residency program performance. AB - OBJECTIVE: To provide national norms for indicators of residency-training program quality and information on their reproducibility. PARTICIPANTS: The 364 residency training programs that had 4 or more candidates take the 1989 to 1991 certifying examination in internal medicine for the first time. DESIGN: Within each residency, program directors' ratings of medical knowledge, certifying examination scores, and certification status (pass or fail) were available for each candidate from 1989 to 1991. Means of these data were calculated for each program for each year of the study. To provide a way of comparing an individual program with all other programs, percentiles are reported for each year. To assess the precision of the measures, generalizability theory was applied and confidence intervals for all data are reported for programs of various size (1 to 25 residents taking the examination) and over the years (1 to 3). RESULTS: Over the 3 years of the study, knowledge ratings, certification rates, and composite scores declined slightly. The correlations between program ratings of medical knowledge and the composite scores ranged from .47 to .60 and certification rates ranged from .44 to .55. The confidence intervals around all of the program performance indicators are relatively large and are affected most by the number of residents in the program. There is little variability across the years. CONCLUSIONS: In smaller programs the precision of the performance indicators is poor; in programs with only a few residents they are virtually meaningless. On the positive side, programs are relatively stable and aggregating indicators over years is a reasonable way to increase their precision in assessing program performance. If the goal of program evaluation is to identify programs at the extremes, especially those at the low end, then such data may help guide program directors and educators. PMID- 7872347 TI - Right lower quadrant pain in a 31-year-old woman with ulcerative colitis. PMID- 7872348 TI - The jaundiced eye: generalism in general. PMID- 7872349 TI - The abscopal effect and chronic lymphocytic leukemia. PMID- 7872350 TI - Chronic mesenteric ischemia: a cause of refractory duodenal ulcer. PMID- 7872351 TI - Neonatal Behcet's disease. PMID- 7872352 TI - The "green water" syndrome: copper-induced hemolysis and subsequent acute renal failure as consequence of a religious ritual. PMID- 7872353 TI - Cardiopulmonary resuscitation in nursing homes. PMID- 7872354 TI - Phosphonoformate for CMV retinitis in AIDS. PMID- 7872355 TI - Ehrlichiosis presenting as a life-threatening illness. PMID- 7872356 TI - Foscarnet or ganciclovir for treatment of AIDS and CMV retinitis. PMID- 7872357 TI - An outbreak of gram-negative bloodstream infections in chronic hemodialysis patients. AB - Six chronic hemodialysis patients acquired bloodstream infections (BSIs) with Klebsiella pneumoniae of the same serotype and similar plasmid profile during an 11-day period. The 6 case-patients were more likely than noncase-patients to have received dialysis during the fourth shift (p < 0.05) and to have their dialyzers reprocessed for reuse after those of the noncase-patients (p = 0.05). Investigation identified a patient during the same shift with an arteriovenous fistula infected with K. pneumoniae. The dialyzer reprocessing technician did not change gloves between contacting patients and their dialyzers in the treatment area and reprocessing the case-patients' dialyzers at the end of the fourth shift. We conclude that the outbreak of BSIs was caused by cross-contamination of the case-patients' dialyzers with bacteria from the gloves of the reprocessing technician and by inadequate dialyzer disinfection. After revised dialyzer reprocessing techniques and glove-changing policies were instituted, no further clusters of BSIs occurred. PMID- 7872358 TI - Subcutaneous low doses of recombinant human erythropoietin in predialysis patients do not interfere with the progression of renal failure. AB - This paper reports a study on the treatment of predialysis patients with recombinant human erythropoietin (r-HuEPO). The haematocrit, haemoglobin, reticulocyte and platelet values as well as creatinine and creatinine clearance evaluated by standard and radio-isotopic methods before, during and after r-HuEPO treatment were determined. The slope of the inverse creatinine versus time curves was studied too. The authors did not observe any variation of the renal function parameters during and after study and suggest their protocol of r-HuEPO administration for predialysis patients. PMID- 7872359 TI - Cholecystolithiasis in patients with end-stage renal disease treated with haemodialysis: a study of prevalence. AB - Gallstones are quite prevalent in western countries (10-20% of adult population), but there are very few data about the prevalence of cholecystolithiasis in haemodialysis (HD) patients. In our study, we found--with real-time ultrasound--a prevalence of gallstones of 16% in patients with end-stage renal disease (ESRD) treated with HD which is similar to the prevalence in a non-uraemic control group matched for age and sex. In most of our HD patients, cholecystolithiasis was asymptomatic. HD patients with cholecystolithiasis were statistically significantly older than patients without gallstones. We found no differences in sex or duration of HD treatment in patients with and without cholecystolithiasis. The prevalence of cholecytolithiasis in patients with ESRD on HD is similar to that of a normal population though some data suggested a higher prevalence in HD patients. PMID- 7872360 TI - Changes in atrial natriuretic peptide and plasma renin activity following changes in right atrial pressure in patients with chronic renal failure. AB - Since it was first discovered in the early 1980s, the role of atrial natriuretic peptide (ANP) in the control of fluid and electrolyte balance and blood pressure has been extensively studied in both health and disease. We report here a study of ANP and its relationship to corresponding changes in right atrial pressure (RAP) in patients with chronic renal failure (CRF) on haemodialysis compared to healthy controls. Although there was a positive correlation between RAP and ANP in both groups, the changes in ANP following changes in RAP between the two groups were not statistically significant. A unique observation was the response of RAP to changes in posture, with RAP falling significantly as expected in healthy controls in contrast to the exceptional absence of a significant fall in patients with CRF. Healthy controls demonstrated appropriate postural changes in plasma renin activity (PRA) despite marked suppression of PRA levels due to salt loading, in complete contrast to patients with CRF who, despite chronic fluid overload and elevated levels of ANP, continued to have grossly elevated PRA levels that failed to change significantly in response to changes in posture. PMID- 7872361 TI - Lymphocytic intracellular pH and Na+/H+ exchanger activity in hemodialysis patients. AB - We have evaluated intracellular pH (pHi) and Na+/H+ exchanger activity in peripheral lymphocytes from 16 patients on regular acetate hemodialysis. All the patients were taking oral NaHCO3 supplementation (30 mmol/day), to maintain predialysis arterial blood acid-base status within normal range (pH 7.36 +/- 0.02, PHCO3- 23.3 +/- 1.2 mM, pCO2 40.9 +/- 1.4 mm Hg). pHi was measured, using the fluorescent probe BCECF (2',7'-bis-carboxyethyl-5,6-carboxyfluorescein), both in nominal absence of bicarbonate (Hepes solution, pH 7.4; n = 10) and in the presence of HCO3-/CO2 buffer system (pH 7.4, [HCO3-] 25 mM, pCO2 40 mm Hg; n = 6). Predialysis pHi did not differ from controls when measured in the presence of HCO3-/CO2 (7.28 +/- 0.04 vs. 7.29 +/- 0.04, p = NS), but was lower in dialysis patients than in normal subjects (7.11 +/- 0.04 and 7.20 +/- 0.02, respectively; p < 0.05) when measured in Hepes solution. This suggested that bicarbonate independent pHi regulation was abnormal in dialysis patients. To further characterize this abnormality of pHi regulation, lymphocytes were exposed to ethylisopropylamiloride, a specific Na+/H+ antiporter inhibitor, in Hepes solution; this maneuver induced a significantly lower decrement in pHi (0.04 +/- 0.04 vs. 0.15 +/- 0.03, p < 0.05) in dialysis patients than in controls, indicating reduced Na+/H+ exchanger activity in the patients. The rate of pHi recovery during the first 30 s after induction of various degrees of cell acidification (pHi range 6.2-7.0), which in the absence of HCO3-/CO2 is dependent on Na+/H+ exchanger activity, was also reduced in the patients as compared to controls (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872362 TI - Renal function in gout patients. AB - Patients with gouty arthritis were examined at Veterans General Hospital to evaluate whether their renal function is impaired and to define the factor(s), if any, of renal function deterioration. A total of 152 cases were included in the study, and the patients were divided into two groups. One group (n = 80) exhibited pure gout without any associated medical problems or preexisting renal disorders. The second group (n = 72) included patients with gout and hypertension. The group with pure gout was further stratified into patients with tophi (n = 21) and those without (n = 59). Seventy-two sex- and age-matched normal adults served as the control group. We found (1) that the renal function was impaired in the pure-gout group when compared with sex- and age-matched normal individuals (serum creatinine 1.56 +/- 0.64 vs. 0.90 +/- 0.16 mg/dl, p = 0.0001; creatinine clearance 59.91 +/- 30.90 vs. 97.10 +/- 27.19 ml/min, p = 0.0001); (2) that the renal function was significantly more aggravated in patients with clinically visible tophi than in those without (gout with tophi vs. gout without tophi: serum creatinine 1.89 +/- 0.90 vs. 1.44 +/- 0.48 mg/dl, p = 0.040; creatinine clearance 47.27 +/- 31.90 vs. 64.40 +/- 29.53 ml/min, p = 0.030), and (3) that a further significant decline of the renal function was noted in gouty patients with an associated medical illness, i.e., hypertension (gout with hypertension vs. pure gout: serum creatinine 2.10 +/- 0.97 vs. 1.56 +/ 0.64 mg/dl, p = 0.0001; creatinine clearance 45.06 +/- 24.69 vs. 59.91 +/- 30.90 ml/min, p = 0.0029).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872363 TI - Considerations on the sodium retention in nephrotic syndrome. AB - Renin-angiotensin-aldosterone system, plasma atrial natriuretic peptide (PANP), and blood volume (BV) have been investigated in 20 nephrotic patients with normal renal function and with (group 1; n = 12) or without (group 2; n = 8) sodium retention. Patients of group 1 had a plasma albumin (PALB) concentration < 1.7 g/dl, low BV and PANP levels, a reduced fractional excretion of lithium (FELi), and high plasma angiotensin II levels. Patients of group 2 had PALB > 1.7 g/dl, and the other parameters were normal. The spontaneous intake of dietary sodium was lower in group 1 than in group 2. In all patients the BV was directly correlated with PALB, and the plasma renin activity (PRA) was inversely correlated with both BV and PALB. A nonlinear inverse relationship was present between plasma aldosterone (PALD) levels and fractional excretion of sodium (FENa). The acute expansion of the BV in patients of group 1 normalized PRA, PALD, PAII, FENa, and FELi and increased PANP. The administration of spironolactone to the patients of both groups had variable effects on FENa, did not modify PRA and PALD, and reduced body weight, PANP, and FELi, thus suggesting that the reduction of BV induced by the drug increased the proximal reabsorption of sodium. Three additional patients who had sodium retention, PALB of 2.3-2.4 g/dl, normal PRA and PALD, elevated urinary excretion of aldosterone, and a slightly low PANP showed a spontaneous normalization of urinary aldosterone and PANP associated with natriuresis and weight loss, but thereafter urinary aldosterone increased, PANP decreased, and the sodium retention began again. Our data suggest that in nephrotic patients with severe hypoalbuminemia, contraction of BV plays a major role in promoting the sodium retention through the activation of compensatory hormonal mechanisms. On the other hand, when PALB is not severely reduced, the patients have normal BV, but they are very sensitive to small changes of BV which are better evidenced by modifications of the urinary excretion of aldosterone and PANP rather than by the profiles of PRA and PALD. PMID- 7872364 TI - Factor(s) present in sera from patients on long-term hemodialysis increase(s) mRNAs for collagenase and stromelysin in synovial cells. AB - Rheumatic disorders are common complications in patients on long-term hemodialysis (HD), and abnormalities of collagen metabolism in the musculoskeletal system have been suggested in these patients. Since collagenase, which catalyzes the initial step in the proteolytic degradation of collagen, plays an important role in the metabolism of collagen, the present study investigated whether factor(s) present in the sera from patients on long-term HD stimulates collagenase gene expression in synovial cells. The addition of sera from 8 patients on long-term HD resulted in 1.5- to 4.0-fold increases in the collagenase mRNA level in human synovial cells as compared with that of sera from normal subjects. The collagenase-inducing factor(s) in uremic sera is more than 3,000 D in molecular mass and shows no binding to heparin. Uremic sera also increased stromelysin mRNA, but failed to exert any effect on mRNAs for tissue inhibitor of metalloproteinases and pro alpha 1(I)collagen. Our findings suggest that there exists a factor(s) to enhance degradation of synovial collagen in sera from long-term HD patients. PMID- 7872365 TI - Role of cocaine in end-stage renal disease in some hypertensive African Americans. AB - During a period of 1 year we observed 12 African American patients who had smoked or sniffed cocaine for several years and presented to inner city hospitals with accelerated hypertension and renal insufficiency. Ten required maintenance dialysis; 1 recovered partially after a brief period of dialysis, and 1 had moderate renal insufficiency. In the absence of striking proteinuria, cardiomegaly or renal shrinkage, the probable diagnosis in most of the patients was primary accelerated hypertension. The clinical history suggested that the habitual use of cocaine had worsened the hypertension, made it more difficult to control or triggered an accelerated phase resulting in renal shutdown. At a time when billions of dollars are being spent on the treatment of end-stage renal disease, the harmful role of cocaine in susceptible individuals requires due attention. PMID- 7872366 TI - Cellular immunity in hemodialysis patients: a quantitative analysis of immune cell subsets by flow cytometry. AB - Immune cell subsets, when measured by two-color flow cytometry in a population of 129 hemodialysis patients, showed significant variance from normal values. Lymphopenia, decreased absolute counts, and altered percentage values of immune cells were found. Increased proportions of CD3+, T cell receptor (TCR) alpha beta + cells and CD4+ T lymphocytes were present. An abnormally high percentage of a subset of activated TCR alpha beta + cells (alpha beta + DR+) was also seen in hemodialysis patients. The proportion of B lymphocytes was found to be significantly lower as compared with controls. Relative values for TCR gamma delta+cells, both for activated (gamma delta + DR+) and nonactivated (gamma delta + DR-) subsets, as well as for CD8+ lymphocytes and natural killer cells did not vary from those of normal controls. Also, the CD4+/CD8+ ratio showed no significant change. Analysis of absolute counts of the investigated immune cell populations revealed significantly decreased numbers for the majority of subsets, as a result of the preexisting lymphocytopenia, characteristic of end-stage renal disease. We conclude that profound quantitative alterations of immune cells, including TCR+T cells subsets, exist in hemodialysis patients. These account, at least in part, for the immune dysregulation associated with chronic renal failure. PMID- 7872367 TI - Comparative effects of low- and high-osmolar contrast media on the renal function during early degenerative gentamicin-induced nephropathy in rats. AB - The nephrotoxic potentials of a high-osmolar contrast medium, diatrizoate, and of a low-osmolar contrast medium, ioxaglate, were compared during early degenerative gentamicin-induced nephropathy in the rat. Male rats (13-22/group) were uninephrectomized. Six days later, the aorta was clamped above the renal artery, and either diatrizoate or ioxaglate was administered (1 ml/min for 3 min) via an aortic puncture into the remaining kidney. Some of the rats received chronic treatment with gentamicin (50 mg/kg/day i.m., 4 days), starting 2 days before and ending 1 day after contrast medium administration. Two control groups, only one of which received gentamicin, were subjected to a 3-min renal ischemia. The creatinine clearance (CrCl) per 100 g body weight was determined before and 24 and 48 h after contrast medium injection. A second study (6 rats/group) evaluated urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion and the histologic appearance of the kidneys (blinded analysis) in the same experimental groups. Gentamicin induced a significant decrease in CrCl at baseline (0.35 +/- 0.19 vs. 0.41 +/- 0.19 ml/min; p < 0.01) and an increase in urinary NAG (128 +/- 92 vs. 39 +/- 57 mumol/h/mmol creatinine; p < 0.01). Taking into account these differences at baseline, univariate repeated-measures analysis showed that on day 1 diatrizoate caused a more marked decrease in CrCl than ioxaglate (p < 0.05), whether or not gentamicin was also administered. On day 2, the depressant effect of diatrizoate associated with gentamicin persisted (CrCl vs. day 0 = -0.19 +/- 0.10 ml/min), while that of diatrizoate alone returned to baseline (-0.05 +/- 0.24 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872368 TI - Treatment of idiopathic renal magnesium wasting with amiloride. AB - We report a case of an 18-year-old female who presented with severe hypomagnesmia due to idiopathic renal magnesium wasting. Only a partial response was noted with magnesium oxide replacement. Treatment with the potassium-sparing diuretic amiloride led to a further rise in the serum magnesium level, a decrease in the fractional excretion of magnesium and improvement in her symptoms. This case demonstrates an effective treatment for idiopathic renal magnesium wasting. PMID- 7872369 TI - Metastatic endophthalmitis in dialysis patients. AB - Metastatic bacterial endophthalmitis is a rare but devastating complication of septicaemia. We present 3 recent cases occurring in dialysis patients. Septicaemic dialysis patients seem particularly prone to staphylococcal endophthalmitis which developed in the face of therapeutic serum concentrations of appropriate antibiotics in all 3 cases. Prompt treatment, including consideration of intravitreal antibiotics, is required if vision is to be preserved. Early signs of endophthalmitis should be actively sought in septicaemic dialysis patients, as they are easily overlooked. PMID- 7872370 TI - Right-sided bacterial endocarditis due to Flavobacterium odoratum in a patient on chronic hemodialysis. AB - Bacterial endocarditis, particularly involving the left side, has been shown to occur in patients in regular hemodialysis. We report a case of right-sided endocarditis characterized by a very torpid evolution. Although the diagnosis was suspected early in the course, confirmation was obtained 2 months after the onset. Flavobacterium odoratum was identified in the fourth month of evolution and only after multiple blood cultures had been obtained. We believe the very low infectivity of F. odoratum and its very slow growth in culture media prevented an early diagnosis. PMID- 7872371 TI - Modulation of renal osteodystrophy by extrarenal production of calcitriol. AB - We report a patient with severe chronic renal failure who developed spontaneous bone fractures. He was found to have hypercalcemia, normal calcitriol levels (probably due to extrarenal production by noncaseating granulomas), and functional hypoparathyroidism. The bone biopsy showed low bone turn-over and the presence of noncaseating granulomas. Treatment with corticosteroids decreased the calcium and calcitriol levels and the parathyroid hormone levels rose. No further fractures occurred. A repeat bone biopsy revealed the presence of osteitis fibrosa. Renal osteodystrophy may be modulated by extrarenal production of calcitriol. In this case, excessive suppression of parathyroid hormone by endogenous calcitriol presumably caused an adynamic bone lesion and spontaneous fractures. PMID- 7872373 TI - Frontiers in Ovulation Induction. Workshop proceedings. PMID- 7872372 TI - Acute bilateral renal artery occlusion: successful revascularization with streptokinase. AB - A case of acute oliguric renal failure due to bilateral renal artery occlusion is described. The renal function was restored to normal 36 h after the embolic event by revascularization with streptokinase. PMID- 7872374 TI - Pituitary-ovarian interactions during follicular maturation and ovulation. AB - During the past decade, research on hypothalamic-pituitary-ovarian relationships in ovulation has explored the contributions of ovarian steroids and other possible ovarian-derived endocrine factors, such as inhibin, follistatin, and activin. Follistatin and activin probably have a significant intraovarian and intrapituitary function but are not likely to have critical endocrine roles during the follicular phase. Studies carried out with both recombinant and highly purified forms of follicle-stimulating hormone in humans and monkeys indicate that this hormone is the primary stimulant of follicular growth and development. Studies on animals may have led to incorrect emphasis on the local role of estradiol in primate follicular growth. It appears that estradiol is not a critical folliculotropin in humans, although it may have some important direct effects on the oocyte. PMID- 7872375 TI - Ovarian control of follicle development. AB - A variety of ovarian autocrine and paracrine factors may modulate folliculogenesis and steroid production. The developmental program that leads to the production of a dominant follicle involves a precise quantitative and temporal pattern of expression of a large number of genes. Follicle-stimulating hormone plays an essential role in this process, and no other ligand by itself can serve in this regulatory capacity. It is clear that a variety of growth factors can modulate follicle-stimulating hormone action by autocrine and paracrine mechanisms. Advances in the understanding of the role of growth factors, particularly the family of insulin-like growth factor-related proteins, in regulating follicle-stimulating hormone action are discussed. It is likely that complex interactions exist between follicle-stimulating hormone and the growth factors. Significantly, growth factor regulation by pituitary gonadotropins is probably a central feature of their expression. With increased understanding of the ovarian control of follicle development, it is hoped that newer and more effective regimens for synchronous follicular and oocyte maturation can be realized. PMID- 7872376 TI - Endocrine and paracrine control of oocyte development. AB - The effects of gonadotropins on oocyte development are mediated through a variety of mechanisms, including production by granulosa cells of growth factors, cytokines, inhibins, activins, and steroids. Specific receptors for steroids, growth factors, and cytokines have been demonstrated on oocytes of several species. Gonadotropin modulation of follicular concentrations of these paracrine factors may ultimately be responsible for the precise regulation of oocyte function. As gonadotropin-releasing hormone antagonists and recombinant gonadotropins become available, the clinical use of more precise control of the endocrine, paracrine, and autocrine regulation of follicle growth and oocyte development can be more thoroughly investigated. PMID- 7872377 TI - Evolution of clinical agents for ovulation induction. AB - Since the first use of human urinary gonadotropins in the 1960s, the number of agents available for ovulation induction has remained fairly static. However, the nature of gonadotropin therapy is expected to change rapidly in the near future, and by the end of the decade these changes may be augmented by nongonadotropin ovulation induction therapies. Newer agents described in the literature include highly purified preparations of follicle-stimulating hormone and recombinant forms of follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotropin. Protein fragments, cytokines, and growth factors also show great promise as ovulation adjuncts. Other promising approaches being explored are the use of genetically engineered human gonadotropin derivatives, the creation of chimeric proteins, and gene therapy. PMID- 7872378 TI - The role of gonadotropins in ovulation induction. AB - Currently two types of gonadotropin preparations are commercially available for ovulation induction: menotropins and follicle-stimulating hormone (FSH). Proper use of these agents is directed by many factors. Concern about the FSH luteinizing hormone ratio and the bioconsistency of the preparations suggests the use of FSH in most situations. Regimens based on short-term incremental increases in gonadotropin dose (based on frequent sonographic and biochemical monitoring) seem to produce the highest pregnancy rates. Individualization of the patient's ovulation induction course on the basis of history of medication use and the reasons for ovulation induction therapy are also essential to optimize outcomes. PMID- 7872379 TI - Controlled ovarian hyperstimulation regimens in assisted reproductive technologies. AB - The goal of assisted reproductive technologies (ART) is to influence the recruitment of multiple, mature ovarian follicles. Several methods, including spontaneous cycle ART, clomiphene-based ART regimens, and gonadotropin regimens with and without adjuncts, are used. The controversies surrounding these techniques and their relative advantages and drawbacks are reviewed. PMID- 7872380 TI - Micromanipulative and conventional insemination strategies for assisted reproductive technology. AB - Micromanipulative techniques, such as subzonal insemination and direct intracytoplasmic sperm injection, are used when standard in vitro fertilization techniques have failed. These new approaches are currently under investigation in a variety of centers across the country. The projected results and the strengths and weaknesses of these techniques are reviewed. PMID- 7872381 TI - The empiric use of gonadotropin therapy and intrauterine insemination. PMID- 7872382 TI - Adjunctive agents in ovulation induction. PMID- 7872383 TI - Monitoring the ovulation induction cycle. PMID- 7872384 TI - Ovulation induction in the poor responder or hyperresponder. PMID- 7872385 TI - Clinical analysis of excimer laser photorefractive keratectomy using a multiple zone technique for severe myopia. AB - PURPOSE: In an investigational procedure, excimer laser photorefractive keratectomy for severe myopia was performed at three clinical trial centers to determine the effectiveness of the multiple zone technique. METHODS: A VisX Model Twenty/Twenty excimer laser (VisX, Santa Clara, California) was used to perform photorefractive keratectomy on 14 severely myopic eyes (-10.37 to -24.5 diopters) of 12 patients by using a multiple zone technique. Postoperative follow-up ranged from six months to two years; retreatments were performed on four patients, with a follow-up of at least nine months. RESULTS: At six months postoperatively, before retreatment, three of the 14 eyes were within 2 diopters and seven of the 14 eyes were within 4 diopters of attempted correction. Regression of effect to more severe myopia was worse in five eyes treated with nitrogen gas blowing. Retreatments also demonstrated considerable myopic regression. Three patients had loss of two or more lines of best-corrected visual acuity, and these patients also had moderate or severe levels of haze. CONCLUSION: Excimer laser photorefractive keratectomy for severe myopia using a multiple zone technique is associated with considerable regression, haze, and loss of best-corrected visual actuity, especially when performed in association with nitrogen gas blowing. PMID- 7872386 TI - Topographic determination of corneal asphericity and its lack of effect on the refractive outcome of radial keratotomy. AB - PURPOSE: The normal human cornea flattens peripherally. The amount of flattening, or asphericity, has traditionally been calculated from multiple keratometric measurements. We devised a mathematical technique for determining asphericity from computed corneal topography. We then determined whether asphericity affects the refractive outcome of radial keratotomy. METHODS: One eye each of 41 patients who underwent four- or eight-incision radial keratotomy and preoperative computed corneal topography was identified retrospectively and analyzed. The asphericity, P, of each cornea was calculated by fitting Baker's equation (y2 = 2r0x-Px2) to each meridian of the topographic map. For each patient, we calculated the difference between the refractive outcome in diopters for radial keratotomy and the prediction of a quadratic least-squares best-fit model involving optical zone size and age. RESULTS: Aspericity could be calculated from the topographic maps in all 41 patients and ranged from 0.33 to 1.28, with mean +/- S.D. of 0.82 +/- 0.21. Aphericity varied among the meridians of a cornea, with an average standard deviation among meridians of 0.17. No statistical correlation was found between calculated asphericity and refractive outcome. CONCLUSIONS: Corneal asphericity can be calculated from corneal topographic maps. Asphericity is not constant in the different meridians of a normal cornea. Corneal asphericity is not useful in predicting the refractive outcome of radial keratotomy. PMID- 7872387 TI - Topical fibronectin ophthalmic solution in the treatment of persistent defects of the corneal epithelium. Chiron Vision Fibronectin Study Group. AB - PURPOSE: We sought to evaluate the efficacy of topical fibronectin ophthalmic solution, containing 3.5 mg/ml of human fibronectin, in the treatment of persistent epithelial defects of the cornea. METHODS: In a double-masked, randomized clinical trial, patients with a persistent, corneal epithelial defect of at least 14 days in duration, and at least 2 mm in width along the larger axis, were sought from the practices of 38 clinical investigators. After a 14-day washout period, 65 patients were randomly assigned to one of three treatment groups. One group (n = 20) received fibronectin drops; the second (n = 23) received drops of the vehicle from the fibronectin solution; and the third (n = 22) received a placebo. RESULTS: After 21 days of treatment, there was no difference in percentage reduction of the corneal epithelial defect size; the average percentage of reduction of defect area ranged from 46.5% to 54.3%. Fibronectin treatment showed a beneficial effect for patients with larger baseline defects (10 mm2 or greater in area); however, no such effect was observed among patients with smaller defects. Defect duration before treatment had a significant effect on outcome (P = .007); defects of longer duration were less likely to decrease in size over the course of the study. CONCLUSIONS: All three treatment groups showed similar reductions in defect size; therefore, this study provides no support for the efficacy of fibronectin treatment of persistent, corneal epithelial defects. Defect duration showed a negative association with reduction in defect size. Because strict control of topical applications during the washout and treatment periods resulted in beneficial responses, physicians should carefully consider the topical medications used by patients who have persistent, corneal epithelial defects. PMID- 7872389 TI - Incidence of cataract surgery in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. AB - PURPOSE: We studied the incidence of cataract extraction in people with diabetes of long duration to determine which factors are associated with higher risk of surgery. METHODS: We recruited a probability sample of all persons receiving care for diabetes in an 11-county area of southern Wisconsin for a prevalence study of diabetic retinopathy. All 2,366 subjects were examined between September 1980 and June 1982. During the slit-lamp examinations, presence of the lens, whether natural or prosthetic, was noted. The subjects were reexamined four and ten years after the initial prevalence study. Occurrence of cataract extraction in the interim between examinations was recorded. RESULTS: In the younger-onset group there was an 8.3% (95% confidence interval, 6.2%, 10.8%) cumulative incidence, and in the older-onset group there was a 24.9% (95% confidence interval, 21.3%, 28.5%) cumulative incidence of cataract surgery in the ten-year interval. Characteristics statistically significantly related to cataract surgery in the younger-onset group in multivariate analysis were age, severity of diabetic retinopathy, and proteinuria. In the older-onset group, age and use of insulin were associated with increased risk. CONCLUSIONS: These data indicate that cataract surgery is a relatively frequent occurrence in people with diabetes. This finding needs to be considered to plan for health care for people with diabetes. PMID- 7872388 TI - Reversal of abnormal corneal epithelial cell morphologic characteristics and reduced corneal sensitivity in diabetic patients by aldose reductase inhibitor, CT-112. AB - PURPOSE: A randomized clinical study was undertaken to determine whether a topically applied aldose reductase inhibitor, CT-112, was capable of reversing the abnormal morphologic characteristics of corneal epithelial cells, as well as the reduced corneal sensitivity, in diabetic patients. METHODS: Thirty-nine diabetic patients were randomly divided into two groups: one group was treated with topical aldose reductase inhibitor (CT-112) in an ophthalmic preparation, and a control group was treated with the same preparation without the inhibitor. Specular microscopy was performed to analyze the morphologic characteristics of corneal epithelial cells before and after the treatment. Corneal sensitivity was measured by means of the Cochet-Bonnet esthesiometer. RESULTS: The anterior surface area of superficial cells in the group treated with CT-112 was significantly decreased from a mean value of 881 to 728 microns2 (P < .0001), whereas the control group showed no significant changes. Corneal sensitivity remained decreased in the control group, whereas that in the group treated with CT-112 significantly improved, from 5.36 to 1.37 g/mm2 (P < .0001). CONCLUSIONS: These results indicate that treatment with topical CT-112 is capable of reversing abnormal morphologic characteristics of corneal epithelial cells and reduced corneal sensitivity in diabetic patients. PMID- 7872390 TI - Increased comfort and decreased inflammation of the eye by cooling after cataract surgery. AB - PURPOSE: Cooling can reduce clinical symptoms and pain caused by traumatic swelling or fracture of extremities. We obtained subjective and objective measures of the effects of cooling of the eyes after cataract surgery. METHODS: Twenty patients with bilateral cataracts were enrolled in this study. For each patient, an ice-cold eye mask was applied over gauze to one operated-on eye for two hours after the operation and was not applied after operation on the other eye. After each operation, the patient rated comfort on a five-point scale. The severity of inflammation associated with each procedure was evaluated by using an infrared radiation thermometer to determine the central corneal temperature and a laser flare-cell meter to determine the cell and flare count, at intervals up to 28 days after surgery. RESULTS: Cooling, applied after the first operation in ten patients and after the second operation in ten patients, statistically significantly increased the patients' comfort level and was associated with a significant decrease in central corneal temperature on days 0, 1, and 3; in cell counts on days 1, 3, 7, and 14; and in flare counts on days 1, 14, and 28. CONCLUSIONS: Cooling increased the comfort level and reduced inflammation after cataract surgery, with no adverse effects. PMID- 7872392 TI - Pressure-dependent changes of the optic disk in primary open-angle glaucoma. AB - PURPOSE: This study was performed to differentiate glaucomatous changes of the optic disk that may be caused by increased intraocular pressure from those that may be pressure independent. METHODS: For 357 patients with primary open-angle glaucoma, the optic disk was morphometrically analyzed, and the intraocular pressure was measured in 24-hour profiles. RESULTS: By performing an intraindividual bilateral comparison, the differences in the maximal intraocular pressure values of the right eye minus the left eye of the same individual were significantly correlated with the differences in neuroretinal rim area and mean perimetric defect of the right eye minus the left eye. No significant correlations were found for the parapapillary atrophy. CONCLUSIONS: The results indicate that the eye with the higher pressure compared with the fellow eye with the lower pressure showed neither a significantly larger nor smaller parapapillary atrophy, which suggests that the papapapillary atrophy, compared with the neuroretinal rim area and the visual field defect, is less dependent or almost independent of an increased intraocular pressure. PMID- 7872391 TI - Ovadendron sulphureo-ochraceum endophthalmitis after cataract surgery. AB - PURPOSE: We examined an 82-year-old woman with delayed-onset endophthalmitis caused by an opportunistic pathogen, Ovadendron sulphureo-ochraceum. METHODS: Tissue obtained during vitrectomy was cultured and examined by light and electron microscopy. An enucleation specimen was examined by light microscopy. RESULTS: The patient had fungal endophthalmitis, with O. sulphureo-ochraceum present in the lens capsule. The eye developed a necrotizing scleritis secondary to O. sulphureo-ochraceum. The patient failed to respond to intravitreous, subconjunctival, and systemic amphotericin B, and the eye was enucleated. CONCLUSION: In this case of O. sulphureo-ochraceum as a human pathogen, the organism caused endophthalmitis after cataract extraction. PMID- 7872393 TI - Long-term observation of retinal lesions in tuberous sclerosis. AB - PURPOSE: To obtain long-term photographic follow-up of retinal astrocytic hamartomas in patients with tuberous sclerosis to learn about their stability or possible growth patterns. METHODS: Sixteen patients with a confirmed diagnosis of tuberous sclerosis and in whom retinal astrocytic hamartomas were photographed before 1986 at the Mayo Clinic underwent a complete ophthalmic examination, and fundus photographs were taken. The new photographs were compared with previous photographs, and changes in size, character, or number of retinal hamartomas were determined. The minimum follow-up period was five years. RESULTS: A total of 37 astrocytic hamartomas were found. Follow-up ranged from almost six years to more than 34 years, with an average of 16 years. Hamartomas in three patients showed progressive or new calcification. In a fourth patient a retinal hamartoma appeared to originate from a site that had been previously photographically documented to be normal. The remaining hamartomas appeared unchanged over the follow-up period. CONCLUSIONS: Although most retinal lesions in tuberous sclerosis remain stable, some become calcified over time. Additionally, new lesions may develop from previously normal-appearing retina. PMID- 7872394 TI - Branch retinal artery occlusion caused by a mitral valve papillary fibroelastoma. AB - PURPOSE: We studied clinicopathologically a branch retinal artery occlusion caused by an embolus from a mitral valve papillary fibroelastoma. METHODS: At initial examination the patient, a 37-year-old woman, had visual acuity of 20/400 in her left eye, and eight months later her visual acuity improved to 20/20. The diagnosis required echocardiographic and radiologic studies to localize the lesion. RESULTS: The mitral valve papillary fibroelastoma was successfully treated with tumor resection involving the mitral valve. CONCLUSIONS: It is important to diagnose intracardiac papillary fibroelastoma, because it can cause recurrent arterial embolization and because it responds favorably to tumor resection. PMID- 7872395 TI - Acute annular outer retinopathy as a variant of acute zonal occult outer retinopathy. AB - PURPOSE: A 23-year-old man developed a rapid-onset, large, dense scotoma that was associated with a peculiar gray intraretinal ring corresponding to the edge of the scotoma and normal fluorescein angiographic findings. This disorder may represent a variant of acute zonal occult outer retinopathy. METHODS: We studied one patient by ophthalmoscopic examination and fluorescein angiography. RESULTS: The patient experienced a short period of concentric enlargement of the scotoma and narrowing of the retinal vessels within the ring, followed by stabilization of the scotoma and slow progressive depigmentation and intraretinal migration of the retinal pigment epithelium within the zone of visual loss. The cause of this disorder, which affects primarily the outer retina, was not determined. CONCLUSIONS: We speculate that this disorder is part of the spectrum of acute zonal occult outer retinopathy and that the gray border, which separates the normal from the abnormal retina, represents an immune ring phenomenon. PMID- 7872396 TI - Deficits in perimetric performance in patients with symptomatic human immunodeficiency virus infection or acquired immunodeficiency syndrome. AB - PURPOSE: We measured the perimetric performance in patients with either acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) disease but without AIDS. METHODS: Light-difference sensitivity in the central field was measured in 74 eyes of 37 patients. The Humphrey Field Analyzer 640, program 30-2 was used. Additionally, 143 eyes of 143 normal control subjects were studied. RESULTS: Mean deviation was significantly reduced in patients with HIV disease compared with control subjects (mean +/- S.E.M., -4.30 +/- 0.52 vs -0.77 +/- 0.15, respectively; P < .0001). Analysis of subgroups demonstrated that patients with lymphadenopathy syndrome or AIDS-related complex (N = 40 eyes; -3.52 +/- 0.41; P < .0001) as well as patients with AIDS (N = 34 eyes; -5.23 +/- 0.97; P < .0001) had a reduced mean deviation. Those comparisons remained significant (P < .0001) when data were analyzed independently for the right eyes and for the left eyes. Corrected pattern standard deviation (3.15 +/- 0.30 vs 1.39 +/- 0.09; P < .0001) was higher in patients with HIV disease compared with control subjects. Again, analysis of subgroups disclosed a significant increase in patients with lymphadenopathy syndrome or AIDS-related complex (2.55 +/- 0.36; P < .0001) as well as in patients with AIDS (3.85 +/- 0.51; P < .0001). Both comparisons remained significant when data were analyzed independently for the right and left eyes. CONCLUSIONS: This study demonstrates visual dysfunction despite normal visual acuity in patients with HIV disease. Our results are consistent with the hypothesis of damage at the neuroretinal level. PMID- 7872397 TI - Safety of a clean air storage hood for ophthalmic instruments in the operating room. AB - PURPOSE: Evaluation of the safety of a laminar flow clean air hood for the sterile storage of ophthalmic instruments in an operating room. METHODS: A ten year retrospective study of 10,524 surgical procedures performed with instruments stored in a clean air hood was conducted at the Mayo Clinic. Cases of postoperative endophthalmitis were identified through review of the diagnostic indices maintained by the ophthalmology department and the institution and through review of individual patient records. RESULTS: The incidence of endophthalmitis in surgical cases in which instruments stored in a clean air hood were used was 0.076% (eight of 10,524 cases). No clusters of infection were identified. CONCLUSIONS: The use of a laminar flow clean air hood provides access to surgical instruments in a high-volume operating room without exposing patients to an increased risk of endophthalmitis. PMID- 7872398 TI - Relapsing acute myeloid leukemia manifesting as hypopyon uveitis. AB - PURPOSE: Although acute lymphoblastic leukemia may masquerade as hypopyon uveitis, acute myeloid leukemia has only rarely been reported to cause this complication, and ocular relapse generally has been associated with evidence of malignant cells at other sites. We studied a patient with acute myeloid leukemia whose only sign of relapse was bilateral anterior uveitis with pseudohypopyon that was refractory to topical and systemic corticosteroids. METHODS: A 26-year old woman with acute myeloid leukemia in remission, who had bilateral anterior uveitis and increased intraocular pressure at initial examination, was studied clinically. Blood films, bone marrow smears, and preparations were examined by using immunoperoxidase staining. RESULTS: Although there was no evidence of leukemia in the blood or bone marrow samples, the cells obtained from the anterior chamber showed myeloblastic leukemic cells with morphologic characteristics similar to those present in the original bone marrow biopsy obtained 14 months previously. Irradiation and chemotherapy were used to kill the malignant cells in the eye and central nervous system. The persisting glaucoma resolved after anterior chamber washout of necrotic tumor cells. CONCLUSIONS: Unusual features of uveitis in this patient indicated that she had a masquerade syndrome, despite normal results of bone marrow and blood film tests. Aspiration of intraocular cellular infiltrate for cytopathologic examination was required to obtain the correct diagnosis and enable treatment to commence without delay. PMID- 7872399 TI - Biomicroscopic evidence of keratoconus with an apex power of 45.5 diopters by videokeratoscopy. AB - PURPOSE/METHODS: We studied a mild case of keratoconus, which had biomicroscopic evidence of keratoconus. With videokeratoscopy, we examined a 55-year-old man with a family history of keratoconus who showed biomicroscopic evidence of bilateral keratoconus. RESULTS/CONCLUSIONS: Videokeratoscopy of the least affected eye showed a map pattern consistent with an inferiorly displaced cone, but surprisingly the apex power measured only 45.5 diopters. Patients with apex power as low as 45.5 diopters can show biomicroscopic evidence of keratoconus. If a central database existed for such unusual cases, eye-care specialists could contribute to it and provide valuable material to researchers trying to improve automated methods to differentiate between normal and keratoconic corneas. PMID- 7872400 TI - Aggressive nevus of the iris with secondary glaucoma in a child. AB - PURPOSE/METHODS: We studied a case of an aggressive iris nevus that caused secondary glaucoma in a child. RESULTS/CONCLUSION: Unlike most iris tumors, this tumor grew from the superior aspect of the iris. The nevus was also unusual because it invaded the trabecular meshwork and caused secondary glaucoma. PMID- 7872401 TI - Melanoma-associated retinopathy. AB - PURPOSE/METHODS: A 64-year-old man with a history of maxillary antrum melanoma had abrupt-onset night blindness and photopsia. RESULTS/CONCLUSIONS: Ophthalmologic examination and electroretinogram suggested melanoma-associated retinopathy. Serum produced a weak but specific labeling of human bipolar cells by indirect immunofluorescence. Complete excision of melanoma may have contributed to low levels of circulating autoantibodies. The identity of the retinal bipolar antigen recognized by melanoma-associated retinopathy autoantibodies is needed for more accurate diagnosis. PMID- 7872402 TI - Sudden increase in intraocular pressure as an initial manifestation of myelodysplastic syndrome. AB - PURPOSE/METHODS: We studied a rare initial manifestation of myelodysplastic syndrome in an 82-year-old woman who had acute secondary glaucoma in the right eye and mature cataracts in both eyes. RESULTS/CONCLUSION: Therapy with glaucoma control medications and cataract extraction in the right eye resulted in expulsive hemorrhage and subsequent enucleation of the right eye. After cataract extraction, examination of the left eye disclosed a central serous retinal detachment and hemorrhage. Histopathologic analysis of the right eye demonstrated myelocytic and lymphocytic infiltration. PMID- 7872403 TI - Macular pseudohypopyon from secondary syphilis. AB - PURPOSE/METHODS: Acute syphilitic posterior placoid chorioretinitis causes visual loss in patients with secondary syphilis. The condition is characterized by vitreitis and large, yellow placoid lesions in the macula. We examined a patient with syphilis who had a serious retinal detachment and an exudative fluid meniscus (pseudohypopyon). RESULTS/CONCLUSIONS: Visual recovery and complete resolution of the chorioretinal lesion occurred after intravenous penicillin therapy. Secondary syphilis should be considered in the differential diagnosis of any patient with a macular pseudohypopyon. PMID- 7872404 TI - Quantitative eye and head movement recordings of retinal disease mimicking spasmus nutans. AB - PURPOSE/METHODS: To investigate whether quantitative head and eye movement recordings can distinguish patients with spasmus nutans from patients with retinal diseases mimicking spasmus nutans. A patient with congenital stationary night blindness was followed up for seven years with electro-oculographic eye movement recordings. RESULTS/CONCLUSIONS: Rhythmic head movements and fine, intermittent, asymmetric, disconjugate, high-frequency, out-of-phase pendular nystagmus were recorded. Eye and head movement recordings of patients with congenital stationary night blindness can mimic spasmus nutans. PMID- 7872405 TI - Hemifacial spasm and osteitis deformans. AB - PURPOSE/METHODS: A patient with osteitis deformans (Paget's disease) and hemifacial spasm underwent magnetic resonance tomographic angiography. Bone modulating bisphosphonates and botulinum injection were administered to treat the hemifacial spasm. RESULTS/CONCLUSIONS: Computed tomography showed marked temporal bone overgrowth. Magnetic resonance tomographic angiography showed no vascular compression of the facial nerve root. The hemifacial spasm failed to resolve with intravenous pamidronate. Subsequent botulinum injection rendered the patient spasm free for 22 weeks. Further research on the use of bisphosphonates in the treatment of pagetoid hemifacial spasm is required. PMID- 7872406 TI - Hourglass-shaped visual fields as a sign of bilateral lateral geniculate myelinolysis. AB - PURPOSE/METHODS: Bilateral visual field defects resembling an hourglass could be produced by bilateral lateral geniculate lesions. We recently encountered such deficits in a 37-year-old woman after an episode of central pontine myelinolysis. RESULTS/CONCLUSIONS: Automated static perimetry demonstrated the congruous visual field defects to involve both halves of the visual field. They were confirmed with kinetic perimetry, and they remained stable for four years. Magnetic resonance imaging demonstrated enhancing lesions characteristic of myelinolysis in each lateral geniculate. PMID- 7872407 TI - Proximity sensor dimmer device used with a slit lamp. PMID- 7872408 TI - Fluorophotometry in myopic phakic eyes with anterior chamber intraocular lenses to correct severe myopia. PMID- 7872409 TI - Scene schemata in memory for spatial relations. AB - Two schema-based hypotheses were developed and tested regarding recall for the following five types of spatial relations: scene-expected relations, two types of scene-unexpected relations, and two types of scene-irrelevant relations. In two experiments, subjects read relations that were described in passages and then recalled the passages. An attention hypothesis states that the amount of attention directed to a relation increases as the relation increasingly deviates from the schema. This hypothesis predicts high recall for unexpected relations, intermediate recall for irrelevant relations, and low recall for expected relations. A retrieval hypothesis states that a schema guides the search for schema-related information. This hypothesis predicts high recall for expected relations, intermediate recall for one type of scene-unexpected relation and one type of scene-irrelevant relation, and low recall for the remaining types of relations that are unexpected and irrelevant. The results of Experiment 1 supported certain predictions of both hypotheses, and the results of Experiment 2 supported the retrieval hypothesis. PMID- 7872410 TI - Effects of memory load on interhemispheric relay. AB - Experimentation with unilateral and bilateral tachistoscopic stimulation (the Dimond paradigm) increasingly suggests that interhemispheric cooperation (bilateral advantage) occurs or increases as a function of task complexity in general and memory load in particular. However, tachistoscopic experimentation with ipsilateral and contralateral field/hand relation conditions (the Poffenberger paradigm) has failed to provide any conclusive supporting evidence. The present investigation comprised a Sternberg "high speed memory scanning" task, modified as a go/no-go task, and formatted into the Poffenberger paradigm. Sets of items to be scanned (memory load) varied in size from one to four. A highly significant effect of load and a significant field/hand interaction were found, but the field/hand/load interaction did not reach significance. We concluded that the interhemispheric transfer time (ITT) metric drawn from this paradigm is not reliably sensitive to increasing memory load. However, our finding of significantly longer ITT in women than in men suggests that commissural anatomy and physiology may be sexually dimorphic. PMID- 7872411 TI - Charles Egerton Osgood: 1916-1991. PMID- 7872412 TI - The voice of reason. PMID- 7872413 TI - Review of research in supportive psychotherapy: an update. AB - Supportive psychotherapy techniques are widely practiced not only for hospitalized or chronically ill psychiatric patients, but also, on a relatively short-term basis, for patients in acute crisis situations. It has also been found effective for patients with medical illnesses to help them develop more effective coping mechanisms, thereby providing a more favorable long-term course of illness. In spite of the growing practice of this approach to therapy, it is apparent that to date neither the number nor the quality of controlled studies of supportive psychotherapy has increased substantially since empirical studies of this form of treatment were reviewed in 1986. However, with its growing acceptance in the field as a body of specific goals, strategies and techniques that can be taught, perhaps we may now expect to see an increase in better designed and controlled studies that utilize objective and measurable assessment techniques, and that include a follow-up of sufficient length to enable valid statements to be made concerning efficacy. PMID- 7872414 TI - Principles of supportive psychotherapy. AB - I have attempted to survey and outline the conceptual differences between expressive and supportive forms of psychotherapy based on the construct of a spectrum with these forms of treatment at each end. As one moves toward the middle of the spectrum, the situation becomes more difficult to define and, to a certain extent, elements of each may be present in the other form of treatment. However, the more that the therapist can consistently maintain an understanding of the differences between these forms of therapy, and the more consistently he or she can apply them in terms of the tactics and the technical interventions used, the more likely is it that the goals of the treatment process will be achieved. If there is too much overlap or if too much confusion exists between the different strategic approaches (and the appropriate tactics involved), the therapist may inadvertently reinforce disturbed and regressive behavior; or the therapist may inadvertently keep the patient from benefiting optimally from the kind of treatment that has been undertaken. There is no way to catalog or describe all of the different available types of intervention, but it is possible to generalize and conceptually predict what the effects are likely to be given the nature of the treatment process being undertaken. The vast majority of psychiatric patients will probably make use primarily of supportive elements in the treatment experience and only a relatively small proportion of the total population will be optimally helped by an expressive treatment undertaking. It therefore becomes necessary to use creative and consistently organized ways of being supportive and to base the choice of tactics on the psychodynamic understanding of the strategy and technique of the therapeutic process. PMID- 7872415 TI - Self psychology, object relations theory and supportive psychotherapy. AB - A clinical theory of supportive psychotherapy that provides an explanatory model for its mode of therapeutic action can be developed through an examination of the work of Heinz Kohut and object relations theorists such as Ronald Fairbairn and D.W. Winnicott. Central to Kohut's theory of therapy is the premise that in the treatment situation a "good object" is provided for the patient in the form of a therapist who will be internalized, and thus mitigate or repair deficits in the self-structure resulting from inadequate early parenting. The object relations theorist Ronald Fairbairn also emphasizes the importance of the "satisfactory transference situation" to therapeutic change consistent with the author's view that fostering and maintaining the positive transference is a critical technical component in at least the earlier phases of supportive psychotherapy. D.W. Winnicott's conception of the "holding environment" is particularly relevant to the "frame" of supportive psychotherapy through such elements as ensuring the "safety" of the therapeutic situation, and the therapist not allowing anxiety and other affects to mount to intolerable and disorganizing levels. Central to the therapeutic posture of these clinicians is the adoption of an intensely emphatic introspective stance vis-a-vis the patient, which is seen was a critical component of supportive psychotherapy. The effective use of empathy aids the maintenance of the positive transference and facilitates the internalization by the patient of aspects of the interactive process in supportive psychotherapy, thus effecting therapeutic change. PMID- 7872416 TI - The role of theory in teaching supportive psychotherapy. AB - Because supportive therapy is not based upon a theory of mind or personality or psychopathology, it should not be thought of as a unique modality of treatment but rather as a body of techniques or tactics that function with various theoretical orientations as a "shell program" functions with a computer's operating system. The therapist's operating system is the theoretical orientation gives direction to his/her interventions. In the past, supportive therapy has generally been explained in terms of its departures from the model of expressive therapy. The techniques and rationales of supportive therapy have now been articulated so that they can be taught along with the techniques and rationales of expressive therapy. It is important that students not absorb the tenets and tactics of expressive therapy as a monolithic model for all therapy. Supervision of psychotherapy should pay ample attention to the "coaching" function aimed at mastering technique, which is as important as teaching about psychopathology or encouraging personal growth. PMID- 7872417 TI - Supportive psychotherapy of the schizophrenic patient. AB - The unimpressive results, in several classic studies, of expressive psychotherapy for schizophrenic patients have led to a neglect of all dynamic psychotherapy for these patients. However, there have been significant advances in psychodynamic supportive therapy over the past two decades and currently it is both well grounded in psychodynamic theory and has an accepted set of strategies and techniques. In this paper, we apply the general principles of psychodynamically oriented supportive therapy to the outpatient treatment of the schizophrenic patient. Outpatient treatment is divided into stabilization and maintenance phases. During stabilization, treatment focuses on building a therapeutic alliance, psychoeducation (including the family where appropriate) and establishing a bilaterally acceptable, clinically effective, pharmacological regimen. In the maintenance phase, the therapist becomes more therapeutically ambitious, particularly in undermining maladaptive, and supporting adaptive, defenses. Handling of the alliance, transference, countertransference, resistance, working through and attenuation (instead of termination) are addressed and illustrated with clinical material. The role of the supportive therapist also includes overall executive responsibility for the entire treatment, management of psychopharmacology, and clinically appropriate referrals for family work, social skills training and vocational rehabilitation. Studies are needed to determine the effectiveness of this treatment approach; further, whether it is applicable to all schizophrenic patients or only to a particular subgroup. PMID- 7872418 TI - Personality disorders: model for conceptual approach and classification. Part II: Proposed classification. AB - In Part II of this article we propose a model for classification of normal and deviant personality types. First, we outline a matrix that classifies normal and deviant behaviors by combining three levels of functioning (normal, neurotic, and borderline) with specific long term behavior types. Second, we describe in some detail eight discrete syndromes that meet criteria for PDs presented in Part I of the article (Vol. 47, No. 4, pp. 558-571, this Journal). PMID- 7872419 TI - A developmental metatheory of psychopathology. AB - The author proposes an integrative model of psychopathology in light of the contemporary need to bridge diverse ideological frameworks. This model has its major foundations in drive, ego, object relations, and self psychoanalytic perspectives as they impact upon interactional patterns of infancy. The chronology of these theoretical orientations is presented as parallel to a changing focus upon different successive stages in the course of individual development. The longstanding controversy between conflict and deficit theories, which undergirds the various schools of thought, is addressed: a developmental orientation is offered as the overriding conceptual connection between them. Conflict and deficit phenomena are regarded as intertwined and not incompatible: Unconscious drives, desires and wishes, ego defenses, and compromise formations as well as object relationship deficiencies and structural voids and defects in the self are combined to encompass a broad spectrum of psychopathology and its sources: the above intrapsychic and interpersonal factors are interfaced with significant reciprocal dyadic (mother/child) and triadic (father/mother/child) influences upon ongoing maturational processes. For heuristic purposes, a fourfold matrix--dyadic deficit, dyadic conflict, triadic deficit, and triadic conflict--is delineated. Clinical characteristics and developmental precursors of each of the four prototypes, especially with regard to early relational events, are examined. PMID- 7872420 TI - A proposal for psychiatric collaboration in managed care. AB - Managed care has significantly expanded the scope of the biopsychosocial model and its meaning to the practice of psychiatry. The most radical change in treatment has come at the expense of the relationship between the patient and the psychiatrist. Increasingly, various clinicians and administrators are being incorporated into the treatment team. Under these circumstances, treatment may be compromised or proceed with great difficulty. At the same time, this complex arrangement offers many opportunities and challenges that may result in shared learning, enhanced quality, and expedited patient care. A framework of collaboration is proposed as a model that best serves the patient, practitioner, and representatives of the third party. PMID- 7872421 TI - Violence in patients with narcissistic personality pathology: observations of a clinical series. AB - This paper presents clinical observations on a group of nine patients whose action consisted of either the commission of violent acts or of seriously threatening behaviors suggestive of precursors to violence. A cluster of common features was observed to be present to some degree in all patients: (1) significant narcissistic personality pathology, (2) recent narcissistic injury, (3) inability to acknowledge or express affect related to this injury, (4) some history of impulsiveness when stressed, and (5) the availability of a weapon. Discussion is presented that the clinician's ability to predict the potential for violence may be enhanced by special attention to these features. PMID- 7872422 TI - Dungeons and Dragons: the use of a fantasy game in the psychotherapeutic treatment of a young adult. AB - A schizoidal young man made a methodical attempt at suicide. He revealed a paucity of object attachments leading to profound isolation. His early upbring led him to extreme isolation of affect and a fear of fragmentation. His inner life was not safely reachable by conventional therapy. After he became involved in playing a fantasy game, Dungeons and Dragons, the therapy was modified to use the game material as displaced, waking fantasy. This fantasy was used as a safe guide to help the patient learn to acknowledge and express his inner self in a safe and guided way. The patient ultimately matured and developed healthier object relations and a better life. The theoretical underpinnings of this process are explored, both in dynamic terms and in terms of the biologic correlation and equivalence of dreams and waking fantasy. The utility of this game as a vehicle for treatment of selected individuals is discussed. PMID- 7872423 TI - A realistic approach to the use of electron microscopy and other ancillary diagnostic techniques in surgical pathology. PMID- 7872424 TI - Immunohistochemistry of MyoD1 in adult pleomorphic soft tissue sarcomas. AB - Adult pleomorphic rhabdomyosarcomas are difficult to distinguish from other pleomorphic soft tissue sarcomas. Immunostaining with the monoclonal antibody MyoD1 5.8A has recently shown promise as a sensitive and specific marker of rhabdomyosarcomas of childhood. To determine the usefulness of MyoD1 in distinguishing adult pleomorphic rhabdomyosarcoma from other pleomorphic sarcomas, we studied 21 cases of pleomorphic sarcoma, including six cases diagnosed as rhabdomyosarcoma. Immunostaining was accomplished using monoclonal antibodies against MyoD1, desmin, alpha-smooth-muscle actin, and muscle-specific actin on cryostat sections of frozen tumor. All cases of pleomorphic rhabdomyosarcoma stained positively with both desmin and MyoD1. Five cases diagnosed as nonrhabdomyosarcomatous pleomorphic sarcomas stained positively with desmin, but only one showed weak MyoD1 positivity. Three of these five cases were also positive with alpha-smooth-muscle actin. The results of this study suggest that the sensitivity and specificity of the MyoD1 antibody in the differential diagnosis of adult pleomorphic soft tissue sarcomas approaches that seen in pediatric rhabdomysarcomas. PMID- 7872425 TI - Pseudoangiomatous stromal hyperplasia (PASH). A mammary stromal tumor with myofibroblastic differentiation. AB - Pseudoangiomatous stromal hyperplasia (PASH) is frequently a microscopic incidental finding in breast biopsies performed for benign or malignant disease. However, it may also produce a mass lesion. We reviewed PASH seen first as a tumor in 40 women aged 14 to 67 years (mean, 37 years). All but one lesion were clinically palpable. The exceptional tumor was found by mammography. The mass, typically unilateral, was usually diagnosed clinically as a fibroadenoma. Most specimens contained a well-circumscribed tumor with a firm white-gray cut surface. In six cases, there was no discrete gross lesion in the surgical specimen. Microscopically, there was a spectrum of pathological stromal changes ranging from classical PASH with anastomosing slit-shaped spaces outlined by flat, bland spindle cells to more proliferative lesions composed of bundles of plump spindle cells that obscured the underlying pseudoangiomatous architecture in the most florid lesions. The spindle cells were vimentin and CD34 positive and factor VIII negative. In more cellular fascicular lesions, the stromal cells acquired desmin and actin positivity. These immunohistochemical features were consistent with myofibroblastic histogenesis of PASH. Reactivity for progesterone receptor (PR) typically exceeded estrogen receptor (ER) in the nuclei of stromal and glandular cells. In most lesions, the nuclei of stromal spindle cells were ER negative. The majority of the patients were treated by excisional biopsy. One lesion, incompletely excised, spontaneously regressed. One patient had bilateral mastectomies. Follow-up was 0.6-11 years (mean, 4.5 years). Five patients had ipsilateral recurrences, and two had subsequent contralateral PASH. The morphological spectrum of cellular proliferation and staining qualities indicates that the myofibroblast plays a major role in the histogenesis of PASH. The pathogenesis of PASH remains uncertain, but aberrant reactivity of myofibroblasts to endogenous or exogenous hormones is likely to be an important factor. Simple excision is adequate treatment initially and for infrequent recurrences, Diffuse PASH occasionally presents a difficult management problem that may necessitate mastectomy. PMID- 7872426 TI - Lipochondral degeneration of capsular tissue in osteoarthritic hips. AB - Lipochondral degeneration (LCD) was found in the capsular tissue of 33 of 74 resected osteoarthritic hips studied retrospectively and in 14 of 35 studied prospectively, but never in a control group (n = 46). The process arose in the ligamentous structures that had undergone nodular chondroid metaplasia. The lesion was characterized by vacuolar distention of chondrocytes, eventual necrobiosis, and formation of acellular pools of lipid material. The latter was shown by oil red O staining and electron microscopy. Matrix alterations included glycosaminoglycan depletion, formation of elastin-related material, and degeneration of collagen fibers. There was no significant correlation (p = 0.05) between the occurrence of LCD and the severity of the osteoarthritis; neither was any association found with age, sex, calcium pyrophosphate dihydrate deposition, diabetes mellitus, or coronary artery disease. PMID- 7872427 TI - Paracortical nodular T-cell lymphoma. Identification of an unusual variant of peripheral T-cell lymphoma. AB - Peripheral T-cell lymphomas (PTCLs) are regarded as diffuse proliferations. We describe an unusual paracortical nodular growth pattern in four nodal PTCLs that were initially interpreted as atypical lymphoid hyperplasia in three patients and small B-cell lymphoma with plasmacytic differentiation in a fourth. The nodules were vague to easily discernible and produced minimal to partial architectural distortion. Sinuses were often open, and scattered cortical lymphoid follicles with atretic to hyperplastic germinal centers were present. Clusters of tumor cells abutted some follicles in all cases, and in one case they exhibited focal T zone expansion. Hypervascularity was not prominent, but a few nodules surrounded epithelioid venules, imparting an angiofollicular appearance. The nodules were composed primarily of small lymphocytes with irregular nuclei admixed with scattered large transformed cells, both cell types having clear cytoplasm. Paraffin immunoperoxidase showed that the nodules were composed of T cells. Dendritic cell networks were present only in follicular centers. Southern blot analysis found T-cell receptor gene rearrangements and a germline immunoglobulin gene configuration in all four nodes. These paracortical clear cell nodules of clonal T cells may be a special type of PTCL. Alternatively, they may represent early foci of lymphoma or they may be a subgroup of T-zone lymphoma. Paracortical nodular PTCL must be differentiated from atypical hyperplastic lesions and some B cell lymphomas. PMID- 7872428 TI - Primary intrapulmonary thymoma. A clinicopathologic and immunohistochemical study of eight cases. AB - We describe eight cases of primary intrapulmonary thymoma occurring in seven women and one man between the ages of 25 and 77 years. Clinically, all patients had initial radiographic findings of a parenchymatous intrapulmonary mass without evidence of mediastinal involvement either radiologically or at surgery. The lesions varied from 0.5 to 10 cm in greatest diameter. Five tumors were located close to the hilum, while the other three were discovered deep within the lung and in subpleural locations. In one case, the lesion appeared to arise endobronchially and infiltrate the surrounding parenchyma. In another case, in addition to the main hilar mass, there were two smaller tumor nodules found deep within the same lung. Histologically, the lesions were characterized by the classic biphasic cellular composition of thymomas, i.e., an admixture in varying proportions of epithelial cells and lymphocytes. Four cases were characterized by sheets of lymphocytes admixed with scattered epithelial cells that were separated by fibrous bands into lobules. Three cases were composed predominantly of sheets of epithelial cells admixed with scattered small lymphocytes and containing prominent perivascular spaces. In two of these cases, focal areas of spindling of the cells were noted. One case was composed predominantly of a spindle cell proliferation with perivascular spaces and numerous small lymphocytes. Immunohistochemical stains for keratin and epithelial membrane antigen in six cases highlighted the epithelial cells scattered against the lymphoid cell background. Seven patients were treated by surgery. In one patient the tumor was deemed inoperable at the time of exploration owing to extensive pleural infiltration and was treated by postoperative radiation; the lesion recurred locally in the pleura 8 years later. Clinical follow-up in three patients after surgical incision showed them to ba alive and well without evidence of disease at 10 months, 2 years, and 8 years, respectively. Two of the patients had been followed clinically for 2 and 4 years following discovery of their lung masses on routine chest radiograph before resection of their tumors. Two patients died of unrelated conditions; in one of them, the lesions had been followed clinically for 6 years before surgery; this patient died 6 months later from coronary artery disease, without evidence of recurrence or metastasis. Our findings suggest that intrapulmonary thymomas are slow-growing tumors that may respond well to surgical resection when confined to the lung. As with their mediastinal counterparts, invasive tumors will require additional treatment for the possibility of recurrence of metastasis. PMID- 7872429 TI - Nuchal fibroma. A clinicopathological study of nine cases. AB - Nuchal fibroma apparently was first described in the second edition of Enzinger's and Weiss's text book in 1988. We have been unable to find any other accounts of this entity. We have reviewed the clinicopathological features of nine nuchal fibromas, eight of which were referred in consultation. Eight patients were men; the ages ranged from 19 to 53 years (median, 43). Patients were first seen with solitary, unencapsulated, subcutaneous swellings in the back of the neck or dorsal region measuring from 2.5 to 8 cm in maximum dimensions (median, 3.5). Macroscopically, lesions were firm, fibrofatty masses. Histologically, there were sheets of hypocellular dense collagen with interspersed mature fat, inconspicuous, small, thin-walled vessels, and entrapped nerve fibers. The picture suggested a fibrolipoma, a lipomatosis, scar tissue, or even elastofibroma, but the small amount of elastic tissue present lacked the beaded, nodular appearance of elastofibroma. Follow-up information was available in seven cases. In follow-up times from 6 months to 19 years (median, 6 years), one tumor was reexcised 4 months after an incisional biopsy and had not recurred 19 months later. None of the others recurred. The lack of a capsule, the entrapment of nerves, and the predilection for the nuchal or dorsal regions suggest that this hypocellular, benign, fibrofatty lesion is a distinct entity and not merely a lipoma. PMID- 7872430 TI - Depressed adenomas of the colon in familial adenomatous polyposis. Histology, immunohistochemical detection of proliferating cell nuclear antigen (PCNA), and analysis of the background mucosa. AB - Depressed adenomas of the colon have been reported more often during the past several years, but there are few reports on the details of their characteristics or behavior. In this study, depressed and ordinary polypoid adenomas, especially those in an early stage, in the large intestine of 28 patients with familial adenomatous polyposis (FAP) were examined macroscopically, by dissecting microscope, and histologically. Proliferating cell nuclear antigen (PCNA) and the density of crypts in the background mucosa around depressed and polypoid adenomas were also compared. Depressed adenomas of < 1.0 mm in diameter showed horizontal growth between the normal adjacent crypts, which often left the normal crypts as islands, whereas polypoid adenomas grow expansively without including remnants of normal crypts. In depressed adenomas, PCNA shifted to the upper part of the crypts, and the background mucosa in their vicinity showed a low density of crypts. These findings indicate that a unique characteristic of growth of depressed adenomas at an early stage is superficial proliferation. PMID- 7872431 TI - Eosinophilic enteritis in northeastern Australia. Pathology, association with Ancylostoma caninum, and implications. AB - While eosinophilic gastroenteritis is considered a rare condition, eosinophilic enteritis without gastric involvement is quite common in northeastern Australia. We present 79 patients with biopsy-proven eosinophilic enteritis, 70 seen since 1987. In 10 patients, eosinophilic enteritis was associated with infection by single, sexually immature, adult hookworms, most positively identified as the common dog hookworm Ancylostoma caninum. An additional 22 patients (of 34 tested) had serological evidence of A. caninum exposure. The essential pathology, i.e., edema and eosinophilic infiltration of the gut wall, ascites, and regional lymphadenopathy, was identical to that seen in eosinophilic gastroenteritis. Additional, more specific features included pathological reactions centered on attached worms, mucosal alterations and ulcers considered to be hookworm bite sites, and submucosal and lymph node granulomas with central eosinophil degranulation and degradation products. Since A. caninum has an almost worldwide distribution, it is probable that A. caninum-induced eosinophilic enteritis occurs outside Australia. We show that the worm is easily overlooked in pathological specimens and that care is required to preserve worms intact for specific parasitological identification. The clinical and pathological features were similar to those seen in another human enteric helminthic zoonosis, anisakiasis. The possibility that there are yet other undiscovered intestinal zoonoses remains. PMID- 7872432 TI - Localized vasculitis of the gastrointestinal tract. AB - We studied the clinical and pathologic findings of 63 patients with localized vasculitis of the gastrointestinal tract, including 35 partial bowel resections, 14 cholecystectomies, five partial pancreatectomies, six appendectomies, one omentectomy, one gastrectomy, and one esophagectomy. Vasculitis was classified histologically as polyarteritis (n = 33), phlebitis (n = 12), Churg-Strauss angiitis (n = 8), small-vessel vasculitis (n = 6), Buerger's disease (n = 2), and giant-cell arteritis (n = 1). Nineteen of 33 cases of polyarteritis affected the small bowel or gallbladder, and nine patients with polyarteritis had elevated serum antinuclear antibodies or rheumatoid factor. Eight of 12 cases of phlebitis affected the right colon; there were giant cells in four of these 12 cases, a history of medication use in seven of eight cases, and no evidence of serum autoantibodies. Short-term follow-up (mean, 5 years) demonstrated that systemic disease developed in six of 23 patients with polyarteritis (four of whom had elevated serum rheumatoid factor or antinuclear antibodies), the patient with giant-cell arteritis, and one of two patients with Buerger's disease. Systemic vasculitis did not develop in patients with other types of vasculitis. We conclude that patients with gastrointestinal phlebitis, polyarteritis without serum autoantibodies, and small-vessel vasculitis have a low short-term risk for the development of systemic disease. PMID- 7872433 TI - Pigmented renal cell carcinoma. AB - A rare case of pigmented renal cell carcinoma is presented. The tumor was yellow, somewhat elastic, and soft with focal gray and tan areas. Microscopically, the tumor was a typical renal cell carcinoma of the clear-cell type. Tumor cells containing brown pigment in the cytoplasm were scattered throughout the tumor. Ultrastructurally, the electron-dense granules consistent with the brown pigment noted at the microscopic level showed a coarse or fine granular matrix with or without homogeneous high electron-dense areas, resembling lipofuscin. However, the nature of the pigment was different from that of lipofuscin by the Masson Fontana method after bleaching and rather similar to neuromelanin. The current case is a rare renal cell carcinoma with pigmentation attributed to abnormally excessive accumulation of neuromelanin pigment. PMID- 7872434 TI - Pulmonary malignant lymphoma of mucosa-associated lymphoid tissue (MALT) arising in a pediatric HIV-positive patient. AB - A malignant lymphoma arising in the lung of a pediatric HIV-positive patient exhibited histologic and clinical features of low-grade B-cell lymphoma of mucosa associated lymphoid tissue (MALT). Clinically, the neoplasm consisted of a 4-cm mass in the left-upper lobe of the lung of a 7-year-old girl. The lung mass was surgically resected. Monoclonal immunoglobulin heavy and light chain gene rearrangements were shown by Southern blot. Monoclonality of light chain expression was demonstrated by immunohistochemistry. Coexpression of Leu-22 (CD43) by the tumor cells supported the diagnosis of lymphoma. The remainder of the pulmonary parenchyma distal to the mass was associated with pulmonary lymphoid hyperplasia/lymphocytic interstitial pneumonitis, which may have been a predisposing factor. Gastric MALT lymphomas have recently been described in adult HIV-antibody-positive patients. Ours represents the first reported case of a pulmonary MALT lymphoma in a pediatric HIV-positive patient. In addition, at age 7, this is the youngest patient reported with a MALT lymphoma. PMID- 7872435 TI - Elastofibrolipoma of the mediastinum. A previously undescribed benign tumor containing abnormal elastic fibers. AB - We report the case of a 57-year-old woman who was found to have a mass in the anterior mediastinum. Surgical excision of the mass revealed a well-delimited lesion 10 cm in largest diameter. Histologically, the mass was composed of mature fat alternating with sclerotic connective tissue, which also contained extensive eosinophilic deposits, similar to the abnormal elastic fibers seen in elastofibroma dorsi. The elastic nature of these deposits was confirmed by elastic staining and electron microscopy. We consider this lesion, which we named elastofibrolipoma, a true benign neoplasm that is characterized by tumoral elastogenesis. PMID- 7872436 TI - J. Bruce Beckwith, M.D., recipient of the 1994 Fred W. Stewart Award. PMID- 7872437 TI - Identification of a new North American hantavirus that causes acute pulmonary insufficiency. AB - In May 1993, a pulmonary disease syndrome with novel clinical and epidemiologic features was identified in the southwestern United States. Healthy young adults developed a febrile prodrome followed by the rapid onset of often lethal acute respiratory distress. Although an infectious disease was suspected, intensive investigations initially failed to identify the causative agent. Multiple specialized microbiology laboratories at the National Center for Infectious Diseases (Centers for Disease Control and Prevention) applied classic serologic and culture methods as well as recently developed molecular biological techniques to samples collected from field investigations of the patients. Serologic tests detected the presence of an active immune response to a hantavirus. Reverse transcription and polymerase chain reaction amplification of RNA extracted from human tissues used primers designed from sequences of known hantaviruses to demonstrate genomic sequences of a novel hantavirus. Immunohistochemistry showed the presence of hantavirus antigens in the endothelium of lung tissues from patients and provided the final pathogenetic link to this group of viruses. These methods were concordantly positive in virtually all samples available from 18 patients with compatible clinical histories identified between January and July 1993. Test results of control subjects and searches for other agents in identified cases were negative. This newly recognized hantavirus causes a novel syndrome of acute pulmonary edema and shock; the pathogenesis is related to the presence of virus antigens in the pulmonary capillaries. The virus may be an important cause of severe and fatal disease presenting as adult respiratory distress syndrome in otherwise healthy persons. PMID- 7872438 TI - Molecular characterization of Vibrio cholerae O139 isolates from Asia. AB - In 1992, a serologically novel clone of Vibrio cholerae, designated O139, caused large epidemics of diarrhea in India and Bangladesh. To determine the extent of the spread of V. cholerae O139 worldwide, 484 V. cholerae non-O1 strains isolated from different patients with diarrhea in Thailand, Indonesia, the Philippines, and Peru in 1993 were tested for agglutination in O139 antisera. One hundred fifty-one of these 484 isolates were examined for genes encoding cholera toxin, zonula occlulans toxin, the repetitive sequence 1, and the toxin coregulated pilin A (the V. cholerae virulence gene complex). Thirty-three percent (122 of 364) of V. cholerae non-O1 strains isolated from different patients with diarrhea in Thailand agglutinated in O139 antisera. Ninety-eight percent (120 of 122) of V. cholerae O139 contained the V. cholerae virulence gene complex. None of the 104 V. cholerae non-O1 strains isolated from patients with diarrhea in Indonesia or the 14 strains from patients with diarrhea in the Philippines were serotype O139. Four different ribotypes were found in V. cholerae O139 isolated in Asia. Twenty-three (47%) of 49 Thai O139 strains examined were of different ribotypes than isolates from India and Bangladesh; V. cholerae strains that were not O1 or O139 that were isolated from flies and water in Thailand 11 years previously in 1981 contained the same V. cholerae virulence gene complex found in V. cholerae O1 and O139. This suggests that other unidentified virulence determinants are involved in V. cholerae O139 pathogenesis. PMID- 7872439 TI - Localization of Borrelia burgdorferi in murine Lyme borreliosis by electron microscopy. AB - Lyme borreliosis is a newly recognized systemic infection with protean clinical manifestations. Because the localization of the causative spirochete (Borrelia burgdorferi) in infected tissues is unknown, we used electron microscopy to find spirochetes in the hearts of chronically infected mice. There were three predominant locations for the spirochete in the hearts. In mice infected for one month or less, the spirochetes were mostly in or around blood vessels. They were either in the lumen or in the perivascular space. Mice infected for more than one month had B. burgdorferi in cardiac myocytes as well, often with clear spaces around them. The third area in which spirochetes were common was collagen fibers; the borreliae were wrapped around fibers with their long axis parallel to the fibers. The number of spirochetes was relatively low, but there was no appreciable decrease in numbers of spirochetes with increasing time postinfection. Inflammatory infiltrates were primarily in the endocardium and pericardium, but spirochetes were generally not in or near areas of inflammation. These data are consistent with previously published information that have identified the heart as a site of chronic infection and inflammation in the mouse. The studies extend our understanding of the behavior of the spirochete in vivo by identifying common locations of B. burgdorferi and by noting the disparity between infection and inflammation. PMID- 7872440 TI - Polymerase chain reaction and a liquid-phase, nonisotopic hybridization for species-specific and sensitive detection of malaria infection. AB - In the present study, we describe a polymerase chain reaction (PCR)-based enzyme linked immunosorbent assay for the detection of malaria infection. The target region of the 18S ribosomal DNA is amplified by a PCR using an 18S rRNA, genus specific, biotinylated (5') and an unlabeled primer (3') pair. The detection probes are digoxigenin-labeled DNA oligonucleotides derived from species-specific rRNA sequences. The amplified fragments are allowed to hybridize with the species specific, digoxigenin-labeled oligonucleotide probes. The oligo/DNA complex is allowed to bind onto streptavidin-coated microtiter plates, followed by incubation with a peroxidase-streptavidin conjugate and a colorimetric-peroxidase substrate. The resulting test demonstrated specificity for the four human Plasmodium species, and was able to detect a level of parasitemia of at least 0.0001% in a laboratory-induced P. falciparum infection in monkeys. This liquid hybridization assay is sensitive, specific, simple, and reliable, with wide applicability in epidemiologic studies, accurate detection of mixed infections, detection of low-level parasitemia, and evaluation of chemotherapy and vaccine efficacy. PMID- 7872441 TI - Factors associated with Taenia solium cysticercosis: analysis of nine hundred forty-six Peruvian neurologic patients. Cysticercosis Working Group in Peru (CWG). AB - In most developing countries, 10% of acute neurologic cases are patients with neurocysticercosis (NCC). Determining specific factors associated with contracting NCC will facilitate its diagnosis and prevention. We examined multiple socioeconomic, demographic, environmental, medical, and behavioral characteristics of 946 Peruvian neurologic patients for a correlation with NCC, which was diagnosed by the highly specific and sensitive electroimmunotransfer blot (EITB) or immunoblot assay. Eighteen percent (172 of 932) of serum samples and 28% (101 of 362) of cerebrospinal fluid samples were EITB-positive. The proportion of EITB-positive persons was similar for all socioeconomic levels. Significant factors associated with NCC were: 1) being born outside Lima, 2) having raised pigs, 3) more than 20 years of age, 4) a history of seizures, and 5) a history of taeniasis. Of these factors, raising pigs is the only one that is amenable to intervention, via improvements in animal husbandry. PMID- 7872442 TI - Neurologic changes in visceral leishmaniasis. AB - Neurologic changes in visceral leishmaniasis (VL) are rarely reported. From January 1992 to April 1993, 111 patients with VL were seen at Soba University Hospital in Khartoum, Sudan. Fifty-two (46%) patients had neurologic symptoms or signs; the most common symptom was a sensation of burning feet. Four patients had foot drop. Five patients had deafness and one patient had multiple cranial nerves palsies. None of our patients had vitamin deficiency or any of the other known causes of neuropathy. Nerve conduction studies in 15 patients showed evidence of axonal degeneration and demyelination, which were confirmed by histopathology and electron microscopy of nerve biopsies. There was no direct parasitic infection of the nerve and there was no neuritis. In most patients, the sensory symptoms disappeared within two weeks in most of our patients after specific anti leishmanial treatment. Motor recovery was much slower. Audiographic studies in five patients with deafness showed it to be sensory-neural. Hearing returned to normal after treatment with sodium stibogluconate. Further studies are needed to define the etiology of the nerve pathology in patients with VL. PMID- 7872443 TI - Tropical spastic paraparesis on the Caribbean coast of Colombia. AB - Tropical spastic paraparesis (TSP) is a retroviral disease characterized predominantly by a chronic myelopathy and progressive leg weakness. Four patients from the northern coast of Columbia with chronic spastic paraparesis and serum positivity for antibodies to human T cell lymphotropic virus type 1 by enzyme linked immunosorbent assay and Western blot are reported. All patients had mixed ethnic origins (white, black, and amerindian). This is the first report of TSP on the Caribbean coast of Colombia. This study extends the geographic boundaries of TSP in the Caribbean basin. PMID- 7872445 TI - Treatment of typhoid fever: randomized trial of a three-day course of ceftriaxone versus a fourteen-day course of chloramphenicol. AB - To compare the efficacy of a short course of ceftriaxone with a standard course of chloramphenicol for typhoid fever, a randomized trial was conducted in 46 patients (30 adults and 16 children) who were blood culture-positive for Salmonella typhi or S. paratyphi. Ceftriaxone was given intravenously once a day for three days to 15 adults at a dose of 2 g/day and to eight children at a dose of 50 mg/kg/day. Chloramphenicol was given orally four times a day to an equal number of patients at a dose of 60 mg/kg/day until defervescence, followed by 40 mg/kg/day for a total of 14 days. Clinical cure without complications or relapse occurred in 19 patients (83%) treated with ceftriaxone and in 20 patients (87%) treated with chloramphenicol (P > 0.05). Four patients with clinical failures in the ceftriaxone group included two with fever lasting six days or more, one with altered sensorium, and one with relapse; three patients treated with chloramphenicol developed leukopenia and thrombocytopenia and were switched to amoxicillin therapy. Bacteriologically, blood cultures of all 46 patients were sterile three days after the start of treatment, and remained so through day 15 of follow-up. These results extend previous observations on the efficacy of ceftriaxone in short courses for both adults and children with typhoid fever. PMID- 7872446 TI - A randomized, double-blind, clinical trial of topical clotrimazole versus miconazole for treatment of cutaneous leishmaniasis in the eastern province of Saudi Arabia. AB - The parenteral treatment currently available for cutaneous leishmaniasis (CL) is painful and potentially exposes patients to serious side effects. Thus, effective, topical therapy would be valuable. We assessed the efficacy of topical 1% clotrimazole and 2% miconazole creams in relation to early healing of lesions in CL in a randomized, double-blind clinical trial in 54 patients with 151 lesions treated for 30 consecutive days. Response to treatment was assessed at two weeks and 30 days and classified as fully healed, size reduced, no change, and size increased or worse. Of 89 lesions treated with clotrimazole, 14 (15.7%) healed fully, 42 (47.2%) were reduced in size, 20 (22.5%) showed no change, and 13 (14.6%) got worse. Correspondingly, in the 62 lesions treated with miconazole, none healed fully, 22 (35.5%) were reduced in size, 16 (25.8%) showed no change, and 24 (38.7%) got worse. The differences were statistically significant (P < 0.001). No side effects were observed. It is concluded that clotrimazole was the more effective of the two imidazoline compounds and is recommended as initial treatment for simple lesions. PMID- 7872444 TI - Activity of azithromycin as a blood schizonticide against rodent and human plasmodia in vivo. AB - We compared the efficacy of azithromycin to the clinical antimalarial doxycycline in Plasmodium berghei-infected mice and in P. falciparum-infected Aotus monkeys. When mice were administered drug orally twice a day for three days, the minimum total dose of azithromycin that cured all mice was 768 mg/kg. Doxycycline at a dose of 1,536 mg/kg cured no mice. The efficacy of fast-acting blood schizonticides (quinine, halofantrine, artemisinin) against P. berghei was augmented by azithromycin. In monkey experiments in which there were two animals per experimental group, azithromycin (100 mg/kg/day for seven days) eliminated parasitemia; azithromycin (30 mg/kg/day) initially cleared 99.8-100% of the parasites with recrudescence in the one completely cleared case. Doxycycline (30 mg/kg/day) cleared 100% of the parasites with recrudescence in both cleared cases. Since azithromycin can be clinically administered at a somewhat higher daily dosage than doxycycline, the data suggest that it may be possible to replace drugs of the tetracycline class with azithromycin in combination with fast-acting blood schizonticides for the treatment of P. falciparum infection. PMID- 7872447 TI - Laboratory and field evaluations of a repellent soap containing diethyl toluamide (DEET) and permethrin against phlebotomine sand flies (Diptera: Psychodidae) in Valle del Cauca, Colombia. AB - The repellency and insecticidal efficacy of Nopikex, a soap formulation containing 20% diethyl toluamide and 0.5% permethrin, was evaluated against a laboratory colony of phlebotomine sand flies (Lutzomyia longipalpis). The repellency of Nopikex soap was also compared with that of a placebo soap against another species (Lu. youngi) in a forest near Tulua, Valle del Cauca, Colombia. In laboratory trials of the soap, no reduction in repellency was seen 4 hr after application, but within 8 hr, repellency decreased significantly to 67.0% of the initial value (P < 0.05) based on calculations of the coefficient of protection (CP). Under field conditions, the soap gave up to 100% protection immediately after application, but within 4 hours its CP value had decreased to a median value of only 44.3%. The placebo soap was also found to be somewhat repellent when compared with no treatment, giving a median CP value of 67.7 immediately after application. No significant mortality was seen in sand flies within 24 hr of exposure to the soap in the laboratory, even in those that had fed on protected volunteers. PMID- 7872448 TI - Mass chemotherapy with diethylcarbamazine for the control of Bancroftian filariasis: a twelve-year follow-up in northern Trinidad, including observations on Mansonella ozzardi. AB - A microfilaria survey was conducted in Trinidad in 1992, 12 years after mass treatment with spaced doses of diethylcarbamazine citrate (DEC-C) for the control of Bancroftian filariasis; 348 persons were examined using thick blood smears and a membrane filtration technique. They included 104 who had participated in the mass chemotherapy campaign in 1980. No Wuchereria bancrofti microfilariae were detected among 66% of the population examined. In 1980, 86 of 592 persons examined were found to be infected with W. bancrofti, 140 with Mansonella ozzardi and 44 with mixed infections, while in 1992, only M. ozzardi infections persisted despite treatment with DEC-C. Of the 104 persons reexamined 12 years later, 46 had M. ozzardi, of which five were new cases, but none had W. bancrofti. During both the 1980 and 1992 surveys, low microfilariae rates for M. ozzardi were observed among those 19 years of age or younger. Of the 302 persons newly examined in 1992, 29 were infected with significantly (P < 0.001) more males (79.3%) than females (20.9%) being microfilaremic. The combined results showed similar prevalence rates for M. ozzardi from 23.3% to 21.6% in 1980 and 1992. Nuclepore membrane filtration and thick blood films were very efficient in demonstrating the presence of microfilariae. The usefulness of these methods and spaced treatment using DEC-C are also discussed. PMID- 7872449 TI - Short report: dispersal of Aedes aegypti in an urban area after blood feeding as demonstrated by rubidium-marked eggs. AB - Strategies for the control of Aedes aegypti during urban outbreaks of dengue or yellow fever assume that this species has a maximum flight range of 50-100 meters. Because Ae. aegypti distributes its eggs among several oviposition sites, we postulated that dispersal is driven by the search for oviposition sites, so an ovipositing female may have to fly much further than 50-100 meters to lay all of her eggs. We developed a method for marking Ae. aegypti eggs with a rare alkali metal (rubidium) and showed that in an urban area, oviposition activity in a single gonotrophic cycle lasts several days and covers an area at least 840 meters in diameter (55.4 hectares). We suggest that current practice for the control of dengue and yellow fever transmission by focal treatments with insecticides 50-100 meters around presumed or confirmed cases is unlikely to be effective. Moreover, source reduction (the elimination of breeding sites) may enhance dissemination of virus-infected mosquitoes by reducing the number of available oviposition sites. PMID- 7872450 TI - Short report: prevalence of hantavirus infection in rodents associated with two fatal human infections in California. AB - Rodents living near two fatal human cases of hantavirus pulmonary syndrome in California were surveyed for evidence of hantavirus infection. Seventeen (15%) (14 Peromyscus maniculatus and one each of P. truei, Eutamias minimus, and Microtus californicus) of 114 rodents tested had evidence (enzyme-linked immunosorbent assay or polymerase chain reaction) of hantavirus infection. This suggests that Peromyscus mice, and P. maniculatus in particular, may be the reservoir for the virus causing this newly recognized disease in California, as previously reported for New Mexico and Arizona. PMID- 7872451 TI - Risk factors for Trypanosoma cruzi infection among children in central Brazil: a case-control study in vector control settings. AB - This population-based case-control study was conducted in northern Goias State, central Brazil, in rural settings under vector control surveillance. One hundred forty-nine children seropositive for Trypanosoma cruzi antibodies, selected in a cross-sectional survey carried out in village schools, were compared with 298 seronegative classmate controls matched for age, sex, and place of residence. Information on potential environmental, familiar, and social economic risk factors for T. cruzi infection was collected during household visits, and interviews with parents and entomologic inspections of domestic and peridomestic environments were conducted. The presence of triatomines in dwellings or evidence of triatomine colonization was found to be statistically associated with seropositivity in children. The presence of exuviae and a report of triatomines indoors or outdoors by householders in the past were strong predictors of an infected child. Children from seropositive mothers had a 3.9-fold increase in the risk of having anti-T. cruzi antibodies after adjusting for the confounding variables, including triatomine capture, mother's age, and family size in multivariate analysis. Parent's report of vector presence showed a 97.7% sensitivity in identifying a dwelling with at least one seropositive child. The possibility of transplacental T. cruzi transmission and its implication for Chagas' disease control were considered. PMID- 7872452 TI - Diarrheal disease among military personnel during Operation Restore Hope, Somalia, 1992-1993. AB - The potential for widespread diarrheal disease was regarded as a substantial threat to U.S. troops participating in the early phases of Operation Restore Hope in Somalia. Outpatient surveillance of 20,859 U.S. troops deployed during the first eight weeks, however, indicated that a mean of only 0.8% (range 0.5-1.2%) of personnel sought care for diarrhea each week, and in three epidemiologic surveys, < 3% of troops reported experiencing a diarrheal illness per week. Despite these low overall attack rates, diarrhea accounted for 16% of 381 hospital admissions and 20% of 245 patients admitted with a temperature > or = 38.5 degrees C. Sixty-one specimens were obtained from inpatients and 52 were obtained from outpatients. Shigella sp. were isolated from 33%, enterotoxigenic Escherichia coli from 16%, Giardia lamblia from 4%, and rotavirus from 1% of 113 stool samples obtained from inpatient (61) and outpatient (52) troops with diarrhea. Bacterial isolates obtained in Somalia were resistant to doxycycline (78%), ampicillin (54%), and sulfamethoxazole (49%), but uniformly sensitive to ciprofloxacin. With the exception of 10 Shigella sonnei isolates that were linked epidemiologically to one eating facility, bacterial pathogens occurred sporadically and demonstrated a wide variation of serotypes and antibiotic sensitivity patterns. Additionally, three of 11 paired sera collected from persons with nausea, vomiting, and watery diarrhea demonstrated a four-fold or greater increase in titer to Norwalk virus antibody. These data indicate that large outbreaks of diarrheal disease did not occur; however, highly drug resistant enteric bacteria, and to a lesser extent viral and parasitic pathogens, were important causes of morbidity among U.S. troops in Somalia. PMID- 7872454 TI - [Awakening and emotions]. PMID- 7872453 TI - Prevalence and epidemiology of Schistosoma mansoni and S. haematobium infection in two areas of Egypt recently reclaimed from the desert. AB - Projects are being carried out in many regions of Egypt to reclaim land from the desert for agriculture. This paper presents findings from a baseline epidemiologic study conducted in 1992 in two newly reclaimed areas near Ismailia, Egypt. In the first area, just east of the Suez Canal, 40.0% of the residents tested positive for Schistosoma mansoni and 1.7% tested positive for S. haematobium, while in the second area, 15 km southwest of Ismailia, 49.3% tested positive for S. mansoni and 3.3% tested positive for S. haematobium. The intensities of S. mansoni infection were moderately high, with a geometric mean egg count of 76 eggs/gram of feces among positive individuals in the first area, and 100 eggs/gram of feces in the second area. When compared with a previous study conducted in 1985, the prevalence of S. mansoni infection in the first area has increased from 21.7% to 42.1% among settlers in the last seven years, while that of S. haematobium has decreased from 7.8% to 1.7%. These trends may result from changes in irrigation practices or other alterations in the local environment. There is a risk of schistosomiasis becoming a major public health problem in reclaimed areas if adequate control measures are not taken. PMID- 7872455 TI - [Awakening from traumatic coma and its future. 3 phases of dynamic reconstruction]. AB - After the question of TC patient's survival in Intensive Care Units, many other questions, during-coma awakening phase, appear to family, care team, and the patient himself i.e. will the patient be handicapped or will he be as before? which after-effects of this passage? The vital functions and autonomy conquest goes with a permanent adjustment of psychical functions for keeping together an "exploded" subject. Each patient's singular history, its expression and meanings, are catched into initial trauma, coma, intensive care and awakening phase framework. Clinical observations leads to describe three evolutive periods, specific of awakening but also bound up with each other. PMID- 7872456 TI - [Is awakening only a dream?]. AB - "It's a dream ..." is the frequent definition of Intensive Care and Coma Experience proposed by patients. Does this word, so insistent and often heard in our research and those of many colleagues, correspond to the objective terms (onirism, confusion, delirium) qualifying clinical awakening or coma (as patients do assert it)? Or doesn't it rather point to a specific status of an other psychical experience? That is the author's hypothesis here developed, through specific aspects of awakening state and therapeutical implications. PMID- 7872457 TI - [Can coma and awakening be evoked in infants?]. AB - This question occurred to me when I had the opportunity to consult an hospitalized nursling in Neonate Unit. I felt him to look like oldest children considered as being in coma. Coma diagnosis has not been evoked neither for him nor for other babies I had to know during their neonate hospitalization. They were described as somnolent, sleepy, flaccid. It seems that coma state could not be considered during their first weeks of life. This difference of impression appeared to me as interesting to question. What possibilities of relations with the nursling does this imply? PMID- 7872458 TI - [Problem infants in pediatrics]. PMID- 7872459 TI - [From prolonged coma to awakening: a guided journey?]. AB - The interruption of human intercourse induced by extended coma is compounded by the deleterious effects of an artificially deprived or understandable anymore could be a traumatic experience in itself. As a result of the many years of work carried out in the Neuro-Surgical service, Orleans-La Source, it seems necessary, when speaking about "enriched surroundings" and "stimulations" for the comatose patient, to associate the notions of personalized care, reawakening of desire, and, by the early introduction of familiar landmarks, to gain access to emotional language. Among all possible means, human attendance seems the most pertinent and efficient route to generate this emotion, when it truly expresses the motives of the attendant. The latter, once his defensive reactions are surmounted, will find his reward in the always important call for global care, and his motivation may be renewed by what seems properly termed as a nascent human relation. PMID- 7872460 TI - [Post-traumatic awakening and "child of the night"]. AB - Clinical configuration of borderline period of awakening is described based on the triangular relation (Patient, Family, Care Team) beginning during coma. The possible suffering before awakening (regressive attitude, downfall of immune defences, and so on ...) evokes a sort of reply of trauma and the hypothesis that mechanisms of "negative hallucination" play a part in post-traumatic amnesia. PMID- 7872461 TI - [Fragments of a past that never existed]. AB - Many patients show maladjusted behavior after the wake up period (weeks or months after) and need a psychological care. To recognise the meaning of parts of behavior, to reconstruct this parts as dislocated pieces of a happened but "unlived" personal experience solve the patient's problem. The examples can be discussed in regard of the question raised by this particular experience. PMID- 7872462 TI - [Plea for interactive rehabilitation during coma]. AB - The question of head trauma reasons, and the shock of traditional family and therapeutic references, make the authors examine clinic coma evolution till awakening. From signs of libidinal values collected by care-team, another way during coma and till life recovery, is rebuilt. PMID- 7872463 TI - [Coma: a new humanistic discipline]. AB - Two researches merge together in this article: the former originates in coma clinical practice and aims at reaching a more abstract formulation, while the latter originates in the theory of narrative and tries to find practical applications. The interest of this merger lies in opening up a new field of study, comatics, whose object is to conceive the best possible conditions for comatose people, for specific varieties of comatose people and even for this or that individual comatose person to fit back into social life, which involves grasping meaning and clues and signals and signs, and finding one's way about in the circuit of communication. Comatics, in short, is semiotics as applied to awakening from comatose states. PMID- 7872464 TI - [The injured patient and the psyche]. AB - This paper aims at presenting a theoretical approach of actual work done for many years with patients awaking from coma. Its general methodology comes from Peircean semiotics and reveals a deep split between a "tone" and a "type". Some of the epistemological conditions that found the treatment of singular cases are here explored. Then a model is built inspired by the Lacan's "phase of mirror", that reveals the way the team refers to the "semiotic recovery" phase. PMID- 7872465 TI - [Psychological aspects of awakening from severe brain injuries: a theoretical approach]. AB - As they take care of brain injured patients from coma to socioprofessional return, the authors suggest a psychopathological pattern of coma and awareness. Psychoanalytics concepts of need, request, wish, object a, fantasy and "Jouissance" allows reflexion on psychic events of awareness and suggest the way of taking care of these patients. Recovery from brain injury combines neurological recovering with nursing people's wish and questions again about the peculiar structure of the human being. PMID- 7872466 TI - [Man, environment and consciousness]. PMID- 7872467 TI - [Conscious, unconscious and not conscious in coma]. AB - In this work, the relation between the consciousness and the unconsciousness was studied in patients presenting a neurosurgical coma state. The study includes 29 patients with clinical observations during their hospitalisation period and a follow up for one year after the emergence from the state of coma. The psychoanalytic methods were used, taking in consideration the emotional and personal history of each patient. We attempted to demonstrate the persistence of the unconscious psychic life during coma and the early period after awakening from the coma. In addition, we felt the existence of a sort of direct confrontation with the unconscious psychic life in some patients emerging from a comatose state. The question is also what are the effects of such experience and how would they affect the life of the patients in the future? PMID- 7872468 TI - [Delusions and dreams during resuscitation]. AB - S. Freud in his "Metapsychological supplement to the theory of dreams" considers dreams and Meynert's "Amentia" as a "Hallucinatory-wishful psychosis". After investigation in resuscitation units and reading of the "Amentia", it seems that this designation by a respectful master of Freud refers to pathological states identical to the ones we observe nowadays with patients getting out of coma. Jensen's "Gradiva" describes a kind of benign madness, since it is an amorous folly. This again is a "Hallucinatory wishful psychosis". Freud tells us that the novel explain precisely how to cure this state. From Meynert's "Amentia" and from Jensen's "Gradiva" commented by Freud, the author goes on with remarks about the illusions of resuscitation and about the means of helping the patient to recover. PMID- 7872469 TI - [Coma--resuscitation--unconsciousness. Approach to a difficult triple connection]. AB - Clinical observations as well as words pronounced by brain injured patients in coma awaking phases attest the emergence of an unconscious psychic register, which arises at the time of coma and resuscitation, and takes an active part in their perspective background during the subsequent phases. Reported clinical fragments illustrate the interconnections between this unconscious register and the various physiological breakdowns suffered by patients as well as their attempts to recover this background. PMID- 7872470 TI - [Talking to an "unconscious" patient?]. AB - In our every day practice in intensive care unit, we have the constant worry to join words to our care, is it towards conscious our unconscious patients. This paper is the issue of a work of listening and thinking over from the nursing team, to the testimony of a patient who was in our unit for three months. This person was in the coma for long weeks, and he tells us afterwards about how he experienced this trial. PMID- 7872471 TI - [Dissidence of a psychologist...]. AB - Among comatose or awakening subjects, psychoanalysis is able to theorize and to interpret clinical practice. For all, it is not possible to refer, for such subjects, to psychoanalytical practice. PMID- 7872472 TI - [Awakening from coma and respiratory weaning]. PMID- 7872474 TI - [Awakening from coma, psychic aspects. Proceedings of a symposium. Strasbourg, France, 20-21 March 1993]. PMID- 7872473 TI - [Programmed coma, called anesthesia, used as a model]. AB - Some kind of anaesthesia could be able to be used as theoretical models to build both hypothesis about awakening and methods for its study. There are codified anaesthesia for short operations, using few drugs with well known pharmacology. Studying awakening requires circumstantial screens to identify awake marks. Such a screen has been used for some years in this type of anaesthesia given for voluntary pregnancy termination. Similar but not identical marks are observed while the subject drop asleep and awake. They seem approximate marks observed with other screens used for coma awakening survey. But an interpretation of this marks, necessarily cautious, is usable only inside these anaesthetic conditions; if so, psychological explanations appears no more but no less useful than bio pharmacological one. PMID- 7872475 TI - Acute facial paralysis: evaluation and early management. PMID- 7872476 TI - Substernal goiter: a clinical review. AB - Thyroid disease is a very common problem, but indications for surgery are few. We have seen a large number of patients with multinodular goiter. The main indications for surgery in thyroid disease include fear of malignancy, tracheo esophageal compression, and cosmetic reasons. Tracheo-esophageal compression is most commonly noted in patients with mediastinal goiters. Substernal goiter is defined as those situations in which at least 50% of the gland is in the mediastinal location. Although its incidence has decreased, it remains prevalent in almost every country in the world today. SSG is best diagnosed by a thorough history and physical examination, complemented by airway films, fiberoptic laryngoscopy, and computerized tomography. The most common presenting symptoms are those produced secondary to compression effects. SSG show a poor response to medical treatment. Moreover, given their propensity to cause acute airway symptoms, surgical treatment should be considered in most cases. Extirpation of the gland is best performed through a collar incision, with the addition of a median sternotomy in select few and difficult cases. Median sternotomy is necessary in only 1% to 2% of cases. Operative mortality is negligible, and the incidence of complication is minimized by following strict surgical principles. PMID- 7872477 TI - Imaging modalities in the follow-up of non-iodine avid thyroid carcinoma. AB - INTRODUCTION: The treatment of primary thyroid cancer requires protracted follow up because of to the possibility of the development of recurrent metastases many years after the initial diagnosis. Often such follow-up involves imaging at regular intervals with diagnostic I-131 studies. However, not all thyroid cancer concentrates I-131. The purpose of this article is to review the efficacy of alternative diagnostic imaging modalities for follow-up of thyroid carcinomas that do not concentrate radioiodine. MATERIALS AND METHODS: These procedures include the use of nuclear medicine imaging with thallium-201 (TI-201), Tc-99m sestamibi, Tc-99m pentavalent dimercaptosuccinic acid (DMSA), radiolabeled anti carcinoembryonic antigen antibodies, and radioiodinated-131 meta-iodobenzyl guanidine, as well as computerized x-ray tomography, magnetic resonance imaging (MRI), and ultrasound (US). RESULTS AND CONCLUSION: Thallium-201, MRI, and pentavalent DMSA provide adequate sensitivity for follow-up of selected patients with suspected recurrent noniodine concentrating thyroid carcinoma. PMID- 7872478 TI - The histology of laser thermo-chondro-plasty. AB - INTRODUCTION: Giving a new shape to a cartilage graft has been a matter of continuous study. In 1991, our group managed to change the shape of human nasal septal samples using CO2 irradiation. This procedure, which we call thermo chondro-plasty, was achieved without the macroscopic carbonization or ablation of the tissue. METHODS: To study the thermo-chondro-plasty effect of the CO2 laser irradiation on human nasal septal cartilage, samples were irradiated in selected laser parameters and then examined with light and electron microscopy. RESULTS AND CONCLUSION: We believe that it was primarily the proteoglycan component of the matrix in which we induced the maximum alterations. The destruction of their water-binding ability led to an uneven reduction of the interlocked tensile stresses of the cartilage and resulted in its transformation. PMID- 7872479 TI - Direct intratumoral embolization of juvenile angiofibroma. AB - INTRODUCTION: Embolization is a well-established technique that facilitates the subsequent surgical removal of vascularized tumors such as juvenile angiofibroma. However, there is risk of a neurological accident during angiography and tumor embolization from the internal carotid artery. Direct intratumoral embolization may help prevent these potential side effects. METHOD: A group of 7 patients with juvenile angiofibroma vascularized through the branches of the internal carotid artery underwent direct tumoral embolization under general anesthesia. An injection made slowly with an intranasal or lateral percutaneous route with either a mixture of cyanoacrylate, lipiodal, and tungsten powder. Continuous radiographic control was used. RESULTS: This technique induced a marked devascularization and necrosis of the tumor. The technique provided useful perioperative visualization of the tumor. No neurologic sequelae were encountered. CONCLUSION: Direct intratumoral embolization deserves further consideration. This might be especially important in tumors with extracranial extension, cavernous sinus involvement, or those with small or multiple recurrences. PMID- 7872480 TI - Haemophilus influenzae type B epiglottitis after immunization with HbOC conjugate vaccine. AB - INTRODUCTION: US Food and Drug Administration (USFDA) has licensed four Haemophilus influenzae type B (Hib) vaccines for use in children. Haemophilus influenzae type B is by far the most common pathogen in childhood epiglottitis and it is hoped that with the introduction of the Hib vaccine that a corresponding decrease in epiglottitis cases will be appreciated. MATERIALS AND METHODS: A retrospective study of all children admitted with the diagnosis of epiglottitis for the 11-year period of 1982 to 1992 was conducted in order to determine the incidence of epiglottitis and Hib vaccine failure. Fifty-nine cases were included in the study by documentation of an inflamed epiglottis. The case of Hib epiglottitis in a 4-year-old child immunized with HbOC conjugate vaccine at 18 months of age is detailed. RESULTS: A statistically significant decrease was found in the incidence of epiglottitis since introduction of the vaccines; however, the overall trend in decrease for the 11-year period was not statistically significant. Vaccination status was difficult to accurately document with only two cases of vaccine failure identified. CONCLUSION: The incidence of Haemophilus influenzae type B epiglottitis at our regional Children's hospital has decreased since the introduction of the Hib vaccine. Reasons for vaccine failure are postulated. PMID- 7872481 TI - Unusual complications of otitis media. PMID- 7872482 TI - Recent developments in piezoelectric immunosensors. A review. AB - The development of piezoelectric (PZ) devices as immunosensors is reviewed. The recent advances in sensor design have stimulated great interest in PZ technology and facilitated diverse applications in a variety of matrices. Methods of antibody immobilization on crystals and several applications are reported including microgravimetric immunoassays, microbial toxins and other contaminants. PMID- 7872483 TI - Electroanalytical and biocompatibility studies on carboxylated poly(vinyl chloride) membranes for microfabricated array sensors. AB - Potassium ion-selective and pH membrane electrodes based on neutral carrier ionophores for K+ (valinomycin) and H+ (TDDA and ETH 5294), respectively, immobilized in carboxylated PVC (PVC-COOH) with normal (classical) and reduced amounts of plasticizer, were investigated with respect to their general analytical performances (linear range, slope, detection limit, selectivity, internal membrane resistance), their biocompatibility and cellular responses. The analytical performance of potassium selective electrodes was not affected by reducing the plasticizer content from 66% (m/m) to about 33% (m/m) while that of pH electrodes was significantly changed at the lower plasticizer concentration level. The adhesive properties of PVC-COOH membranes to an inert substrate such as polyimide-coated Kapton are greatly improved by reducing the plasticizer content of the membrane. In addition, as was reported earlier by this group, improved biocompatibility was observed with these membranes relative to those with increased plasticizer content. A ratio of 1:1 m/m for PVC-COOH to plasticizer is recommended for the construction of planar ISEs without massive use of internal solution. PMID- 7872484 TI - Evaluation of an ammonium ionophore for use in poly(vinyl chloride) membrane ion selective electrodes: solvent mediator effects. AB - A macrotetrolide nonactin-based ammonium ionophore (AI) preparation containing 25% nonactin optimized for use in liquid membrane ion-selective electrodes was investigated for its possible use in poly(vinyl chloride) (PVC) matrix membrane type electrodes. Nine different plasticizing solvent mediators were employed in the ammonium ion-selective membranes with PVC and the AI preparation. Near Nernstian responses were observed in aqueous solution with electrodes fabricated with dioctyl sebacate-, 2-nitrophenyl phenyl ether-, dibutyl sebacate-, trioctyl phosphate-, dioctyl adipate-, dioctyl phenyl phosphonate- and 2-nitrophenyl octyl ether-plasticized membranes. The responses of these electrodes were found to improve in the presence of a background concentration of non-interfering calcium ions. PMID- 7872485 TI - Application of the quadratic response surface in the polarographic determination of lead: biological samples. AB - Differential-pulse polarography was applied to lead determination in blood, urine and hair samples after pressurized acid digestion. Quantitative determination was carried out using a single analytical measurement of the experimental sample (without the need for addition or calibration methods), using the equation calculated as a result of the study of the quadratic response surface. The elimination of the possible interferences has been considered. The reliability of the analytical procedure was evaluated using relative standard deviations (2.34 11.93%) and recovery (97.28-103.92%) measurements. PMID- 7872486 TI - Radioimmunoassay for the determination of alosetron in human urine and saliva. AB - The development of a radioimmunoassay (RIA) for the sub-ng ml-1 determination of alosetron, a potent and selective 5HT3 receptor antagonist, in human urine and saliva is described. The antiserum was raised in Soay sheep following primary and booster immunizations with an immunogen prepared by conjugating alosetron-p azobenzoic acid to bovine serum albumin (BSA). The radioligand consisted of alosetron specifically 125-iodinated on the 2-position of the imidazole group. The mean (+/- standard deviation) theoretical sensitivity (minimum detectable dose corresponding to the imprecision of the zero standard) of the RIA is 3.2 +/- 2.6 pg ml-1 (n = 12) of alosetron in assay diluent (0.1% m/v gelatine-0.05% m/v sodium azide in 0.1 mol l-1 phosphate buffer solution, pH 7.4). The working calibration range using 0.1 ml samples of saliva and 20-fold diluted urine is 0.10-6.40 ng ml-1 of alosetron. Urine samples were diluted prior to assay to overcome adverse matrix effects; consequently, the lower limit of quantification for undiluted urine is 2.0 ng ml-1 of alosetron. Inter- and intra-assay bias and imprecision over the working calibration range were generally < +/- 12% and < 13%, respectively, except at the 0.10 ng ml-1 alosetron level, where the corresponding values were < +/- 17.3% and < 20.2%. The antiserum was free from adverse cross-reactivity with either a synthetic precursor of alosetron or with four major metabolites of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872487 TI - Determination of aluminium by instrumental neutron activation analysis in biological samples with special reference to NBS SRM 1577 bovine liver. AB - It was found that a well thermalized heavy water-moderated research reactor can be used to determine the Al content of biological samples without separation of P, Na and Cl. The contribution of the 31P(n,alpha)28Al reaction was corrected from the known concentration of P and the measured effective value. It was found that the contribution is only about 10%. A method is suggested for the determination of Al using instrumental neutron activation analysis. PMID- 7872488 TI - Enzyme linked immunosorbent assay for ceftazidime in airborne samples. AB - A simple and rapid enzyme linked immunosorbent assay (ELISA) method for the cephalosporin, ceftazidime, has been developed for the quantification of this antibiotic in solutions that have been eluted from filters following the capture of air samples in the workplace. The assay has the specificity, sensitivity and precision necessary for its use in determining airborne concentrations of ceftazidime in the workplace as part of an occupational health and hygiene programme. PMID- 7872489 TI - Rapid method for the determination of total mercury in urine samples using cold vapour atomic fluorescence spectrometry. AB - A rapid method for the determination of total mercury in urine samples is proposed. Samples are digested using a bromination procedure at room temperature. Analysis is performed using automated continuous flow vapour generation coupled to atomic fluorescence spectrometry. This approach allowed the analysis of 30 samples per hour and a limit of detection of 1 ng l-1. The analytical procedure was assessed using certified reference material NBS 2672a freeze-dried urine and two batches of Seronorm trace elements in urine samples. PMID- 7872490 TI - Spectroscopic evaluation of interactions among trace elements and biogenic carbonates in the marine environment. AB - The interactions between trace elements and biogenic carbonates (marine mussel shells) in aqueous media were evaluated. The behaviour of Mn, Cu, Co, and Cd was investigated using spectrometric techniques (electrothermal atomic absorption, inductively coupled plasma atomic emission and electron paramagnetic resonance). The results obtained show that the metals considered do not form a distinct precipitated phase on the shell surfaces, but that they interact with the CaCO3. This study aimed to provide more information on the mechanisms involved in the storage of trace elements by the shells of marine bivalves. This would allow the use of mussel shells as an alternative to soft tissues for trace metal analyses in biological monitoring programmes. PMID- 7872491 TI - Mass spectrometric methods for studying nutrient mineral and trace element absorption and metabolism in humans using stable isotopes. A review. AB - Mass spectrometric methods for determining stable isotopes of nutrient minerals and trace elements in human metabolic studies are described and discussed. The advantages and disadvantages of the techniques of electron ionization, fast atom bombardment, thermal ionization, and inductively coupled plasma and gas chromatography mass spectrometry are evaluated with reference to their accuracy, precision, sensitivity, and convenience, and the demands of human nutrition research. Examples of specific applications are described and the significance of current developments in mass spectrometry are discussed with reference to present and probable future research needs. PMID- 7872493 TI - Quantitative morphology of the ovine seminiferous epithelium. AB - Ultrastructural features and morphometric values of ovine Sertoli and spermatogenic cells are reported with special reference to the 6 stages of the seminiferous epithelial cycle. Seminiferous tubules occupy about 83% of the testicular parenchyma. Average tubular diameter (about 275 microns) and epithelial height (about 95 microns) do not vary significantly during the cycle. From preleptotene to late diplotene the cellular volume of primary spermatocytes increases nearly five-fold; the nuclear volume increases three-fold in the same period. Secondary spermatocytes are observed exclusively during stage 4 of the seminiferous epithelial cycle. Due to partial cell necrosis and autolytic events, ovine spermatids lose a considerable amount of their cytoplasm during acrosome and maturation phases prior to spermiation. Sertoli cells occupy between 27.6% (stage 3) and 36.6% (stage 1) of the tubular epithelium. The average volume of a Sertoli cell varies between 6380 microns 3 (stage 2) and 7195 microns 3 (stage 4), the absolute surface area between 10550 microns 2 and 12305 microns 2. The irregularly contoured Sertoli cell nucleus contains a vesicular nucleolus and occupies about 7.5% of the cell. Mitochondria (about 5%) and smooth endoplasmic reticulum are other prominent organelles, but three-quarters of the Sertoli cell are taken up by cytoplasmic matrix with a well-developed cytoskeleton. Ovine Sertoli cells contain large basal lipid droplets, but no typical lipid cycle can be observed. PMID- 7872492 TI - Localization of cathepsin D in rat ocular tissues. An immunohistochemical study. AB - Numerous studies have demonstrated that cathepsin D as a major lysosomal acid protease plays an important role in the degradation of protein in several tissues. An important function of the retinal pigment epithelium is to interact with the photoreceptor cells in the renewal process. During the renewal process, the RPE cell phagocytosis discarded photoreceptor discs which are then degraded in the RPE phagolysosomes. It is believed that cathepsin D plays a main role in the degradation of rod outer segments and rhodopsin into glycopeptides. The cellular localization of cathepsin D immunoreactivity was examined at the light microscopic level in the ocular tissues of non-affected RCS-rdy+ rats strain by use of the alkaline phosphatase-antialkaline phosphatase (APAAP) technique. The presence of cathepsin D immunoreactivity was found in the cell cytoplasm of the following ocular tissues: retinal pigment epithelium; Muller cells; ganglion cells; pigmented and non-pigmented ciliary body; iris tissue; epithelium and endothelium of the cornea; endothelium of various vessels, including the tunica vasculosa lentis. High activity of cathepsin D was found in the RPE cells, as well as in the cytoplasm of Muller cells, especially expressed in their foot plates lying close to the inner limiting membrane. PMID- 7872494 TI - The morphology of xenotransplanted human breast carcinoma MX-1 growing in nude mice. A light and transmission electron microscopic study. AB - The present investigation is concerned with the morphological features of the human breast carcinoma MX-1, transplanted subcutaneously into nude mice. Three weeks after transplantation the tumor tissue is clearly distinct from the dermis. Solid tumor cell groups are separated incompletely by thin connective tissue septa, giving rise to a lobular appearance. The tumor cells are characterized by very irregularly formed nuclei with three or more nucleoli. The cytoplasm of these cells displays some lysosomes, the cisternae of the rough endoplasmic reticulum, mitochondria and a variable number of ribosomes. The Golgi fields are frequently observed, particularly near the nucleus. The cells are connected to each other by desmosomes, which also persist during mitotic activity. Ductular formations can occasionally be seen. The ultrastructure of the blood vessels discloses the morphological features necessary for the regulation of blood flow. Capillaries present a sinusoidal aspect with distended and narrow lumina. Interruptions of the endothelial wall, however, were not observed. This morphological appearance was found in all the MX-1 tumors investigated, reflecting the stable growth of this tumor cell line in nude mice. PMID- 7872495 TI - Ultrastructure of bovine von Ebner's salivary glands. AB - Bovine von Ebner's glands were studied by electron microscopy. The gland consists of tubulo-alveolar adenomeres which open into an abbreviated duct system. The cells of the secretory acini show many morphological features typical of serous cells and contain numerous granules with a complex substructure. Short intercalated ducts connect the acini with excretory ducts which are lined with bistratified epithelium. The striated ducts are absent. The von Ebner's gland morphology was compared with that of the same gland in other species of mammals and with the ultrastructure of the major bovine salivary glands. PMID- 7872496 TI - Lectin histochemistry of snout skin and foot pads in the wolf and the domesticated dog (Mammalia: Canidae). AB - The distribution and selectivity of complex carbohydrates in the snout skin and the foot pads of the wolf and the domesticated dog were studied by means of light microscopic histochemical methods, particularly lectin histochemistry. In the snout, moderate to strong staining reactions were confined to intercellular substances among the epidermal cells, containing neutral glycoconjugates (glycoproteins, glycolipids) with various saccharide residues (alpha-D-mannose, beta-N-acetyl-D-glucosamine, alpha-N-acetyl-D-galactosamine, beta-D-galactose). In the foot pads, distinct reactions were found in neutral glycoconjugates of intercellular substances of the stratum corneum, with alpha-N-acetyl-D galactosaminyl and beta-N-acetyl-D-glucosaminyl residues, but only in the wolf, whereas in the dog such substances were concentrated in the spinosal and basal epidermal layers, additionally marked by D-galactose. The eccrine glands exhibited high amounts of mainly neutral glycoconjugates in the secretory portion, especially in the wolf. A clear spectrum of saccharide residues was demonstrable in the dark cells (alpha-D-mannose, beta-N-acetyl-D-glucosamine, alpha-N-acetyl-D-galactosamine, alpha-D-galactose), and in the clear cells which lacked mannose and contained beta-D-galactose. In contrast to the wolf, strong reactions for glycoconjugates were visible among intercellular substances of intradermal excretory duct cells in the dog. Only in the wolf did the periphery of the intracorneal excretory ducts and the outer surface of the foot pads show clearly positive reactions for glycoconjugates. The results obtained are discussed with regard to the specific functions of the body regions investigated and the behavioural biology of the Canidae. It is obvious that differences in amounts, quality, and localization of the glycoconjugates produced exist between the wolf and its domesticated descendant. PMID- 7872497 TI - Notes on the organization of the rostral diencephalon of the atherinomorph swordtail-fish Xiphophorus helleri. AB - By using conventional histological methods, the nuclear organization of the rostral diencephalon of the swordtail-fish, Xiphophorus helleri (Poecilidae, Atherinomorpha, Teleostei) was analyzed and compared with those from other teleost species. The subdivisions of the entopeduncular region, especially in their relative position and cytoarchitectonic structure, reveal clear differences between the various teleost orders. A new nucleus, the lateral entopeduncular nuclear area (leNA), found within this region, is described. PMID- 7872498 TI - [The symmetrical relation of intestines, the habenular nuclei and the intestinal venous system in dorsal-doral and ventral-ventral grown parabiontic larva of mountain salamanders (Triturus alpestris)]. AB - Embryos of the newt Triturus alpestris were fused in their dorsal regions (DD parabionts) of their ventral regions (VV-parabionts), while the longitudinal axes were in equal direction. In these parabionts situs and symmetry of the gut, the heart, the habenular nuclei and the vitelline vein were studied. The fusion of the embryos of the DD-parabionts was performed in three developmental stages (after Harrison): phase of neurulation (14-18, N-parabionts), late phase of neurulation (19-22, E-parabionts) and tail bud stage (23-27, S-parabionts). VV parabionts were only fused in phase of neurulation (14-18). The external development of the parabionts in most cases was normally. DD-parabionts showed a more or less pronounced deformation of their longitudinal axes. In DD-parabionts all organs developed separately in nearly all cases. In VV-parabionts a partial fusion of the heart was sometimes observed, while fusion of large part of gut occurred regularly. In DD-parabionts complete and incomplete inversions of all organs and the vitelline vein are extremely abundant in the N-parabionts, much lower in E-parabionts and nearly absent in S-parabionts. The differences are statistically of high significance. The "pair situs" symmetries of N-parabionts (DD-parabionts) show always a strong dominance of a transindividual organ- and vitellin vein-symmetry. In VV-parabionts (N-parabionts) the tendency for inversion of the asymmetric organs is statistically significant lower as in DD parabionts. In regard to this observation there is a preference for an asymmetric "pair situs" in the heart, habenular nuclei and vitelline vein system. In "polarisied" DD-parabionts ("left" as well as "right" parabionts) the asymmetric organs as well as the vitelline vein system inversions were more often observed in the "left" parabiont compared with the "right" parabiont in N- and E parabionts. These right-left differences partial are statistically significant (P < 0.05). The organ situs-correlation as well as the situs-correlation between vitelline vein and gut or heart, respectively, are mostly positive (concordant). The frequency of dominance of "left" organ inversions argues against a morphogenetic "left dominance" of the amphibian embryo. The determination of organ-asymmetries is irreversible only after the end of neurulation in tail-bud stage. The results suggest the efficiency of a "symmetry-factor", which determines the organ symmetry during neurulaphase. The differences between DD- and VV-parabionts are statistically significant and point to a dorso-ventral polarity of the embryo, with a maximal morphogenetic potency in the dorsal region. PMID- 7872499 TI - A histochemical study on the enzymatic activity in the proximal epiphysis of the humerus during the prenatal and postnatal periods in rats. AB - In order to investigate the activity of certain enzymes [Alkaline phosphatase (ALP), Acid phosphatase (ACP), Adenosine triphosphatase (ATPase), 5'-Nucleotidase (5'-N)] in the proximal epiphysis of the humerus, tissue specimens were obtained from pregnant rats on the 15th, 17th, 19th and 20th days of gestation and on the 1st, 10th, 20th, 30th, 40th and 60th days of postnatal development. Enzymatic activity in the chondral ossification, in the perichondral areas of the epiphysis, was first seen on the 15th day of gestation. ALP and ATPase could also be observed for the first time in fetuses aged 15 days, whereas ACP and 5'-N could not be detected. These latter enzymes were observed for the first time in the proximal humeral epiphysis of fetuses aged 17 days. ALP, a marker for hypertrophic and calcifying cartilage, was observed extensively in the central hypertrophic part of the cartilaginous perichondral zones, which showed calcification during the development of the epiphysis. ALP, ATP and 5'-N activity was very marked in the cytoplasm of osteoblasts and in the periosteal matrix, but strong ACP activity was found in the cells of the chondrolysis zone. In conclusion; according to our observations, heterogeneity of the proximal epiphysis of the humerus exhibits intrinsic differences between the cells of different zones. The activity of all enzymes showed an increase according to the developmental age. This suggests that all of these enzymes play a role during developmental ossification. PMID- 7872500 TI - Scanning electron microscopy of the endomysial collagen in the rat paravertebral musculature. PMID- 7872501 TI - A persistent functional artery connecting the thyrocervical trunk and the aortic arch. Embryonic remnant or important aortic vas vasorum? AB - During the dissection of the neck region of a 56 year old female cadaver an artery was found branching from the thyrocervical trunk as a fourth branch and entering the aortic arch on its superior posterior aspect between the brachiocephalic trunk and the left common carotid artery. Selective angiography revealed that this artery branched into several arterioles at its junction on the superior aspect of the aortic arch between the brachiocephalic trunk and the left common carotid artery. No similar structure could be found in the literature. Evaluation of this phenomenon according to our knowledge of the development of human arterial networks, it was concluded that the artery might be a persistent intersegmental artery, or an enlarged nutrient artery (vas vasorum) to the aortic arch. PMID- 7872502 TI - Variation in human infraorbital nerve, canal and foramen. PMID- 7872504 TI - The spermatozoal volume as indicative of the plasma membrane integrity (modification of the hypoosmotic swelling test). I. Methods. AB - The aim of the present study was to establish a more differentiating indicator of plasma membrane integrity of spermatozoa than the classic version of the hypoosmotic swelling test according to Jeyendraan. Spermatozoa were prepared by density gradient centrifugation (90% Percoll) to select 'fertilization competent' spermatozoa only. After a second washing procedure sufficiently pure sperm cell suspensions were obtained. The volume distributions of these sperm cells were measured with a Coulter Counter at 25 degrees C after adaptation in 300 mosmolar NaCl solution resp. 150 mosmolar NaCl solution for 5 min. These volume distributions showed significantly different patterns for the isotonic and hypotonic stress situation in the simple salt solution. Moreover, the comparison of the response to hypoosmotic stress showed more than four reproducible characteristic patterns, promising well differentiated results for different sperm populations. The new method for the detection of hypoosmotic swelling effect might be a real and valuable functional parameter. PMID- 7872503 TI - A rare case of absence of the celiac trunk: the left gastric, the splenic, the common hepatic and the superior mesenteric arteries arising independently from the abdominal aorta. AB - This report describes a rare case of absence of the celiac trunk, which was encountered in a Japanese female cadaver in the dissecting room at Kurume University School of Medicine in 1993. In this case, the left gastric, the splenic, the common hepatic and the superior mesenteric arteries arose independently in that order from the abdominal aorta. In addition, the left aberrant hepatic artery arose from the left gastric artery. This anomalous case belongs to type 5 (Typus primitivus) of Morita's classification (1935), and is the fifth case of this kind of vascular variation to be reported in Japan. PMID- 7872505 TI - The spermatozoal volume as indicative of the plasma membrane integrity (modification of the hypoosmotic swelling test). II. Diagnostic approach. AB - If using a method of statistical sifting based on the Kolmogoroff-Smirnov test for differentiation of volume distribution curves of a modified HOS-test, different curve types are obtained under isotonic as well as under hypotonic conditions. Arrangement of spermatological parameters of the relevant ejaculates according to the individual curve types reveals significant differences for motility. No correlation can be seen with the results of the microscopic HOS test. Consequences for the use of the modified HOS-test in medical practice are discussed. PMID- 7872506 TI - Human sperm movement assessed with the Hamilton-Thorn motility analyzer and in vitro fertilization. AB - The relationship between sperm movement characteristics obtained by computerized analysis and the in vitro fertilization rates of human oocytes was studied. In 144 consecutive in vitro fertilization treatments a sample of prepared semen was analysed by a Hamilton-Thorn Motility Analyzer. In addition a visual estimation of sperm count and motility was made. Significant correlations with the fertilization rate were found for all visual parameters. Of the computerized measurements, the mean velocities of motile spermatozoa and the concentration of motile cells were significantly correlated. The average path velocity correlated best (r = 0.42, P < 0.001). There was no relationship between the percentage of motile sperm showing hyperactivated movement and the fertilization rate. A forward stepwise logistic regression analysis selected the following variables of predictive value for fertilization: average path velocity, male factor infertility as indication for in vitro fertilization, motility and concentration, as measured by the Hamilton-Thorn analyzer. A logistic regression model to predict the cases with low (< 0.2) or high fertilization rates, included the average path velocity as a significant variable and classified the samples with 90% overall accuracy. IN CONCLUSION: movement characteristics of spermatozoa in culture medium, especially the average path velocity are of prognostic value in prediction of human oocyte fertilization rates. PMID- 7872507 TI - Development of an objective and manual technique to study the human sperm morphology. AB - The aim of the present paper is to present results of sperm morphology using an objective and manual technique by video image. Experiment 1:252 spermatozoa heads were measured in a microscope and in a monitor by each of three independent observers. The results allowed the calibration of an acetate overlay according to the WHO guideline and following the strict criteria. Experiment 2: 10 morphology slides from normal and abnormal patients were studied. These slides were evaluated by three independent observers, each counting at least 200 cells using the calibrate acetate overlay. In the first experiment the calculation of the regression out-put was: constant: 0.24, standard error of Yc: 0.04, R squared: 0.96, X coefficient: 0.36, and standard error of the coefficient: 0.03. In the second experiment, it can be seen that the differences among the operators are not statistically significant and therefore the experiment is independent from the operator. In conclusion, the methodology developed in this paper for the evaluation of morphology would be a good tool for the evaluation of human sperm morphology. PMID- 7872508 TI - Difference in DNA index of seminomas and non-seminomas. AB - Flow cytometric examinations were performed consecutively on fresh tumor tissue of 90 patients with testicular germ cell tumours. Measured parameters were the DNA index, the stem-cell shoulder fraction (SSF) as an expression of mitotic activity, and the incidence of tumour population above 5c (5c-exceeding events). The results were correlated with the type of tumour, as determined histologically, the local and clinical stage of the tumour, and clinical outcome. In 94.5% of the cases, flow cytometry detected malignant testicular tumour tissue. The median DNA index in the 53 nonseminoma patients was 1.53, in the 37 seminoma patients, 1.82 (P < 0.01). Four out of 42 patients with nonseminomas had progressive disease. These few patients were more likely to have an increase in the S-phase fraction or a positive 5c-ee index than patients without progressive disease. In 24 patients with nonseminoma, it was also possible to examine lymph node tissue. Lymph node metastases were detected in 92.8% of these cases through aneuploidy: the median DNA index was 1.57, which corresponded to that of the primary tumours. This study confirmed the value of flow cytometry for rapid, automatic diagnosis of malignancy in testicular tumours. The method could aid in discriminating between seminomas and nonseminomas. PMID- 7872509 TI - Quantitative analysis of spermatogenic DNA synthesis in the rat using a monoclonal anti-5-bromodeoxyuridine antibody. AB - The utility of the 5-bromodeoxyuridine (BrdUrd) labelling technique for the quantitative analysis of spermatogenic deoxyribonucleic acid (DNA) synthesis was investigated in the rat. Rat testicles were labelled by a single intraperitoneal injection of 100 mg kg-1 of BrdUrd. The testicles were removed 1 h after injection, fixed in Bouin's fluid and embedded in paraffin. BrdUrd-labelled cells were detected by immunohistochemical staining using a monoclonal anti-BrdUrd antibody. The number of BrdUrd-labelled tubules per total number of tubules (percent L.T.), the number of BrdUrd-labelled cells per total number of tubules (tubular ratio) and the number of BrdUrd-labelled cells per number of Sertoli cells (Sertoli cell ratio in BrdUrd-labelled cells) were calculated as indices of spermatogenic DNA synthesis during each stage of the seminiferous epithelial wave. BrdUrd labelling was found exclusively in the nuclei of spermatogonia and in preleptotene spermatocytes in the seminiferous epithelium. The percent L.T. was generally greater than 50%, except in stages VI, VII and XIV, and the tubular as well as Sertoli cell ratios in BrdUrd-labelled cells was greater than 2.0 and 0.15, respectively, in stages I, II-III, V, VIII, X, and XII. The tubular ratio and Sertoli cell ratio in BrdUrd-labelled cells along the seminiferous epithelial wave had two distinct peaks. The distribution of the tubular ratio using the BrdUrd-labelling technique correlated well with the distribution previously established by measuring tritiated thymidine uptake per tubule. Thus, the BrdUrd labelling technique, which is more efficient than the tritiated thymidine labelling technique, can be used to quantitatively evaluate spermatogenic DNA synthesis. PMID- 7872511 TI - [Recommended methods for the determination of catecholamines and their metabolites in urine. Significance of results in the diagnosis and follow-up of pheochromocytoma and neuroblastoma]. AB - Laboratory investigation of catecholamines is useful for the clinician in the diagnosis and management of phaeochromocytoma and neuroblastoma. This work summarizes current knowledge on catecholamines and their metabolites and discusses the main indications for their determination. It also examines the most practical methods for studying the secretion of these hormones, ie extraction, separation and quantification using high performance liquid chromatography coupled with electrochemical detection. The workshops attended by the members of the catecholamines working party of the French Clinical Biology Society and phaeochromocytoma and neuroblastoma specialists enabled the role of such determinations in the diagnosis and management of these diseases to be clarified. PMID- 7872510 TI - The relationship between ejaculated ram sperm mitochondrial protein synthesis and motility. AB - D-chloramphenicol, at concentrations of 20 and 40 micrograms/ml, inhibited over 80% of the newly synthesized mitochondrial proteins expressed by incorporation of 3H-amino acid mixture. At concentrations of 20 and 40 micrograms ml-1, D chloramphenicol enhanced the collective motility of washed ram spermatozoa. The collective motility measured by the multichannel Reflectospermiograph system, significantly enhanced the motility wave frequencies and amplitudes by 24-17% and 65-32%, respectively. Furthermore, the longevity of the collective motility was prolonged by 12-19%. In about 20% of the cases, when the original sperm motility was low, it was found that 40 micrograms ml-1 D-chloramphenicol has maximum stimulation effect on sperm motility in inverse fashion. Since the mitochondria are located adjacent to the motility initiation area, it can be speculated that the mitochondrial protein(s) directly inhibiting the axonemal-ATPase activity or indirectly blocking sperm metabolite, are essential for maintaining sperm motility. PMID- 7872512 TI - Improved enzymatic assay for plasma hydroperoxides, inactivation of interfering enzymes. AB - The involvement of free oxygen radicals in the pathology of certain diseases explains the growing interest in the assay of lipid peroxides. Assay of polyunsaturated fatty acid degradation products is currently performed by measuring the so-called thiobarbituric acid-reacting substances, of which malondialdehyde is the best known. The fact that this assay is controversial and that a second index of free radical attack would be useful to confirm the peroxidative process prompted us to undertake this work. We propose an improved enzymatic technique for assay of lipid hydroperoxides in biological fluids. Our aim has been to improve the technique already described by Heath and Tappel, which cannot be used as described by the authors. In fact, the presence of endogenous enzymes such as glutathione peroxidase and glutathione reductase in the sample interferes with the reaction and makes the results unreliable. Elimination of these endogenous enzymes by deproteinization before assay of the lipid hydroperoxides in the plasma gives a simple, reliable, and reproducible assay if the experimental procedures described in this work are followed. PMID- 7872513 TI - [Comparison of indirect immunofluorescence on Crithidia luciliae of Farr test, and immunoenzymatic methods for the screening of anti-native DNA autoantibodies]. AB - Anti-native DNA (ds DNA) antibodies were measured by the Farr assay, an indirect immunofluorescence on Crithidia luciliae (IIFCL) and a newly commercialised enzyme-linked immunosorbent assay (Elisa) in the sera of 270 patients: 73 negative controls, 67 patients with systemic lupus erythematosus (SLE), 73 with clinical symptoms of another connective tissue disease and 61 patients with liver diseases. The Farr assay remains a reliable method, IIFCL seems to be as specific but less sensitive and Elisa has a higher sensitivity but a lower specificity. Finally, 35 sera from the 270 patients were tested for anti-ds DNA antibodies using two other commercialised Elisa-related techniques. The results suggest little correlation between the three Elisa methods. PMID- 7872514 TI - [Free amino acids in fetal urine and prognosis of renal function in bilateral obstructive uropathies]. AB - In order to evaluate renal function, fetal urine was sampled in 27 fetuses with urinary tract obstruction diagnosed by ultrasonography. Amino acid concentrations were measured retrospectively. On histological examination performed after termination of pregnancy, five fetuses were found to have bilateral renal dysplasia (group 1). Eleven fetuses developed renal failure after birth: at one year, plasma creatinine concentration was over 50 mumol/l (group 2). Renal function was normal in the 11 other infants (group 3, plasma creatinine concentration at one year < 50 mumol-1). Statistically significant between-group differences were seen in fetal urine amino acids concentrations. However, there was an overlap of values in the three groups and individual amino acid concentrations could not be used predictively. PMID- 7872515 TI - Measurement of apolipoproteins B and A by radial immunodiffusion: methodological assessment and clinical applications. AB - The clinical evaluation of apolipoproteins is of interest in order to characterize the risk profile for ischemic heart disease both in normolipidemic and hyperlipidemic subjects. In the non-specialized and/or small practice clinical laboratory, the measurement of some apolipoproteins can be undertaken by simple methods of immunological analysis, among which radial immunodiffusion can be of interest due to its simplicity of use and because it does not require specific equipment. In this work several methodological questions concerning the measurement of plasma apolipoproteins B and A by radial immunodiffusion have been addressed; the results show that this method is particularly reliable for the apo B assay. Regression analysis between values obtained with radial immunodiffusion and radioimmunoassay was r = 0.972 for apo B and r = 0.782 for apo A. The recovery rate was above 90% for both apolipoproteins (93.8% for apo B and 99.5% for apo A). The inter and intraassay coefficients of variation were below 5%, and the detection limits were estimated as 9.6 mg/dl for apo A and 6.9 mg/dl for apo B. Neither the ingestion of a standard breakfast (500 Cal, 17 g fat, 120 mg cholesterol) 2 h prior to testing nor freezing the sample significantly affected the measurement of apolipoproteins B and A. Mean plasma concentrations of both apolipoproteins measured by radial immunodiffusion in normo and hyperlipidemic subjects are also presented. PMID- 7872516 TI - Serum lipids and atherogenic risk in sickle-cell trait carriers. AB - This work studies the relationship between a common genetic marker in our population, sickle-cell trait, and atherogenic risk factors. One hundred and twenty-two healthy subjects were studied. Forty-six subjects had normal haemoglobin (HB-AA) while 76 had sickle-cell trait Hb-AS. Mean cholesterol level was higher in subjects with sickle-cell trait (2.82 +/- 0.21 g/I) than in subjects with normal haemoglobin (2.08 +/- 0.40 g/I) used as controls. The difference was statistically significant (p < 0.05). HDL cholesterol levels remained in the normal range in controls (Hb-AA) (0.560 +/- 0.10 g/I) while subjects with Hb-AS had high HDL-c levels (0.618 +/- 0.30 g/I). Mean LDL cholesterol levels in Hb-AS subjects were about 57% higher than those in controls (1.84 +/- 0.10 g/I and 1.17 +/- 0.30 g/I, respectively) (p < 0.05). Apolipoprotein A1 levels of Hb-AS subjects were lower (1.37 +/- 0.10 g) than those of Hb-AA subjects (1.98 +/- 0.15 g/I), (p < 0.05) while apolipoprotein B concentrations of Hb-AS subjects were higher (1.70 +/- 0.27 g/I) than in controls (1.30 +/- 0.10 g/I) (p < 0.05). The atherogenicity index given by the Apo-B/Apo AI ratio was higher in Hb-AS subjects (1.24) than in those with normal haemoglobin (0.65). We conclude that Hb-AS subjects are at high atherogenic risk if subsequent diet management is not undertaken. PMID- 7872517 TI - [Effect of the age and the sex on plasma concentration of amino acids]. AB - The effects of age and sex on the plasma free amino acid pattern of healthy men and women aged from 80 to 100 years were compared with those in younger adults (20 to 45 years old). Plasma amino acid concentrations were determined by ion exchange chromatography on a 6300 Beckman analyzer. The plasma concentrations of valine, leucine, isoleucine, proline, glutamine + glutamic acid and phenylalanine were higher in males than in females. Citrulline, half-cystine, histidine, glutamine+glutamic acid, lysine, ornithine and phenylalanine plasma concentrations and the total plasma amino acids were higher in elderly than in younger subjects. PMID- 7872518 TI - [Immunoassay and measurement of the biological activity of serum hLH: results obtained of a multicenter study]. AB - The discrepancy between results obtained using different anti-hLH antibodies available on the market led us (in the context of a contract with the CNAMTS) to compare the results of hLH immunoassays (eight different reagents) with those of hLH bioassays based on the measurement of the steroidal activity of this hormone on mouse, rat or pig testicular preparations (five methodologies). Twenty-nine samples of serum or human serum pools were tested. The values resulting from these tests reveal differences linked to the nature of the antibodies or to the methodological conditions used for the testicular preparations. Some antibodies seem unable to identify some hLH forms which, however, can be detected by biological methods. PMID- 7872519 TI - [The good use of Diprivan (propofol) in anesthesia]. PMID- 7872520 TI - Recommendations for the good use of Diprivan (propofol) in anaesthesia. PMID- 7872521 TI - [Physicochemical interactions and mode of storage of Diprivan]. AB - Only few publications consider physio-chemical interactions and stability of propofol. On the basis of current experience, this agent is safe for use in polypropylene or polypropylene/polystyrene syringes, diluted 1 in 5 in 5% dextrose if necessary. The potential hazards are as follows: 1. Propofol may undergo oxidation when not stored under nitrogen, or when in contact with oxidizing agents (active ingredients or excipients of other preparations). 2. The emulsion may be destabilised by contact with mineral or organic cations (calcium, magnesium, dibasic amino acids etc.) or acids (citric acid etc.). 3. Losses of propofol may occur by adsorption-diffusion (surface adherence combined with penetration of plastic material) during storage in PVC bags or during administration by means of PVC infusion sets. Most of these hazards have still to be evaluated under controlled conditions. PMID- 7872522 TI - [Infectious complications linked to the use of Diprivan. Precaution of administration]. AB - In order to avoid the risk of severe infection by bacterial contamination of propofol, all users of this agent, should be reminded of the required aseptic technique "for the correct use of Diprivan". These points have recently been listed by Zeneca Pharma. They mainly include the following items: 1. Propofol is to be administered immediately after opening the vials and/or ampoules and the duration of the same continuous infusion should not excede 12 hours. 2. Disposable equipment (syringes, infusion sets, 3-way stopcoks, infusion bottles) should be used and restricted to one patient only. 3. One ampoule or vial of diprivan, once opened, must be used for one patient only. The remaining solution must be discarded. 4. Disinfection of the ampoule neck or vial stopper using and antiseptic solution before opening, is a strongly measure recommended. 5. Finally, hand washing should be routine, prior to these manipulations. As far as the above mentioned precautions are strictly followed, this anaesthetic agent may be used safely, even in case of prolonged sedation. PMID- 7872523 TI - [Does the lipid emulsion of Diprivan explain some pharmacological effects?]. AB - In currently available experimental or clinical studies, there is no report of any adverse effect related to the lipid emulsion of propofol, for procedures not exceeding on average four hours of duration. General anaesthesia produced by propofol alone is associated with only moderate alterations of blood lipid concentrations. Therefore there is no restriction to the use of propofol. In the absence of precise data, it is recommended not to use propofol infusion in congenital hyperlipaemias (e.g., hyperchylomicronaemia). The lipid emulsion of propofol may alter the rheological properties of circulating blood, platelet aggregation, chemotactic activity of neutrophils and lymphocytes functions. These alterations are always limited. Furthermore, most studies which have recorded these effects are not directly applicable to clinical practice and additional studies are necessary. There are no data demonstrating that propofol would increase surgical bleeding or the incidence of postoperative infections. Since there is a low probability of these adverse effects, they should not limit the use of propofol. PMID- 7872524 TI - [Pain associated with the injection of Diprivan]. AB - Pain at the site of propofol injection is a real problem which requires particular attention in children. In adults, undergoing planned surgery, premedication or opioid administration prior to propofol seem to sufficiently reduce the frequency and severity of the pain induced by the injection of the agent into a distal arm vein. Adding lidocaine to propofol just before the injection is debatable in day-case procedures, especially if the injection is carried out on the dorsum of the hand. In children, intravenous administration of lidocaine seems to be more routinely performed, whatever the type of surgery. PMID- 7872525 TI - [Diprivan: drug interactions]. AB - Concerning the pharmacokinetic or pharmacodynamic interactions, the following is recommended: Use smaller doses of alfentanil when the latter is combined with propofol, because of a higher risk of ventilatory depression. Decrease doses of each agent whenever propofol is combined with thiopentone or midazolam to induce anaesthesia. The prophylactic or therapeutic use of atropine is indicated when propofol is associated with agents reducing heart rate. Prefer propofol to induce anaesthesia for eye surgery, if suxamethonium is required. In the absence of sufficient data, propofol should be administered with care in patients taking cardiovascular medication (risk of hypotension) or cyclosporine (enhanced toxicity). PMID- 7872526 TI - [Diprivan and liver]. AB - No evidence of hepatoxicity has been demonstrated with propofol. Propofol can be used for anaesthesia in patients suffering from moderate cirrhosis of the liver. Liver blood flow is preserved. Propofol dosage must be titrated to each patient's needs. Data concerning the use of propofol in patients suffering from severe hepatic failure or cholestasis are lacking. Propofol dosage in chronic alcoholic patients without cirrhosis must be increased. PMID- 7872528 TI - [Acute hepatic porphyria and Diprivan]. AB - Propofol may be used without any restriction in all cases of asymptomatic hepatic porphyria, as a bolus injection for induction and maintenance of anaesthesia and as a continuous infusion to produce anaesthesia of short and medium duration. If in doubt as to the absolute safety of propofol in case of symptomatic hepatic porphyria, preference has to be given to neuroleptanalgesia, benzodiazepines and muscle relaxants. If propofol is to be used, treatment with haematin should be readily available. In all cases, it is essential to determine porphyrins and their precursors prior to and after surgery. Urine collection should strictly adhere to the recommended procedure: sterile conditions, protected from light and high temperature. Any abnormal reaction after the administration of a drug, especially propofol, should be notified to and discussed with the National Porphyria Centre (Centre Francais des Porphyries). In case of symptomatic hepatic porphyria the use of propofol should always be notified to the National and to the European Porphyria Centres (Orphan Europe). PMID- 7872527 TI - [Use of Diprivan in renal insufficiency]. AB - The use of propofol for induction and maintenance of anaesthesia in end-stage chronic renal failure has been reported in many publications. The rather minor pharmacokinetic changes of propofol recorded in patients with end-stage chronic renal failure are in favour of the absence of accumulation of agent, and is a good reason for its use in this context. Acute variations in potassium plasma concentrations or acid-base balance have been observed neither in healthy subjects nor in end-stage chronic renal failure, after administration of propofol. Effects of propofol on known impaired renal function have not been studied, apart from renal transplantation. Therefore, postoperative monitoring of renal function is essential, as haemodynamic variations elicited by the administration of propofol contribute to its aggravation. These haemodynamic variations depend on the dose, the rate of administration, the underlying cardiovascular condition and the blood volume of the patient. Due to inter patient variability in clinical and laboratory parameters, the dose required for a stable anaesthesia varies with the each patient. Careful, slow administration ensures easier titration of the required dose, keeping any secondary haemodynamic side-effects to a minimum. In these patients the quality and speed of recovery depends on the type and dose of agents associated with propofol to maintain anaesthesia. Nitrous oxide, in reducing the need for opioids, should shorten the recovery period. Monitoring of cyclosporine blood concentrations after anaesthesia using propofol is mandatory in renal transplant patients. PMID- 7872529 TI - [Use of Diprivan in muscular diseases and malignant hyperthermia]. AB - An unknown myopathy can be revealed by the administration of an anaesthetic agent. The symptoms are those of malignant hyperpyrexia (MH). The MH phenotype can be detected by means of contracture tests in vitro. All anaesthetics, excepting the triggering agents, can be given. The safety of propofol as an induction and maintenance agent in this category of patients has been demonstrated. When the presence of a myopathy is known before an anaesthetic, the administration of succinylcholine associated or not with a halogenated inhalational agent carries a risk of severe complication. Among the anaesthetic agents having little effect on the skeletal muscle, propofol seems interesting, also because of its pharmacokinetic properties. Myopathy is difficult to diagnose, either because the patient undergoes surgery before being symptomatic or because he is only a carrier of MH. In case of an abnormal reaction following the administration of recognized triggering agents or the occurrence of MH, the procedure should be discontinued. In case of absolute necessity, the procedure may be continued but with non-triggering agents only. PMID- 7872530 TI - [Diprivan and epilepsy]. AB - Propofol can be used safely in patients with a history of epilepsy. In the known epileptic patient, propofol is not contra-indicated, provided that the anaesthetist ensures that the anti-epileptic treatment is correctly maintained. PMID- 7872531 TI - [Diprivan: mode of administration and depth of anesthesia]. PMID- 7872532 TI - [Diprivan: efficient concentrations in relation to physiological parameters and associated drugs]. AB - According to the literature there is a large inter-individual variability, with blood concentrations often ranging from 1 to 3-fold. These variations between patients reduce the value of recommended concentrations. In practice it is more important to titrate the dose according to the clinical response (or lack of response), rather than to blindly follow the various dosage regimens proposed and, with which it is theoretically possible to rapidly reach and then maintain the desired propofol concentration. In practice, what is the point of carefully maintaining a propofol concentration of 3.5 micrograms.mL-1 (theoretical maintenance level for an average patient), if the latter (failing to comply with the usual range of concentrations) needs a propofol level of 6 micrograms.mL? In practice, we must titrate! PMID- 7872533 TI - [Duration of anesthesia and mode of administration of Diprivan]. AB - The dosage regimen to maintain propofol anaesthesia should ensure adequate depth of anaesthesia for the procedure, and allow a swift recovery. If the dosage is not adapted to the various phases of surgery, there is a risk of awareness especially after painful stimuli. This awareness is not always announced by signs which would allow its prevention. It is characterized by patient's movements but does not result in a memorization of the episode, except if the patient opens his eyes at that moment. Conversely, if propofol blood concentration is maintained at a sufficiently high level to prevent such unexpected movements, it will be necessary to reduce this concentration in the last stage of surgery to avoid a delayed recovery. Intermittent bolus injections and not controlled infusions are gradually abandoned. The optimal use of propofol should rely on the: 1. Use of an infusion pump (volumetric pump) which ensures regular administration: 2. Correct choice of administration technique, that ensures the most stable anaesthesia regardless of the type of operation, using the least possible amount of anaesthetic agent; 3. Combination of points 1 and 2, the first intellectual step towards progressively acquainting anaesthetists with the simultaneous use of an automated administration associated with a computer, which is the most reliable and effective technique today. PMID- 7872534 TI - [Diprivan: evaluation of the depth of anesthesia]. AB - In daily practice, assessing the exact depth of anaesthesia relies even today on clinical signs such as movements elicited by painful stimuli and/or changes in blood pressure and heart rate. Neurophysiological indicators, such as EEG and evoked potentials, are most probably techniques of the future. They are not yet in routine medical practice, because of the complexity of the information supplied, unresolved technical problems and the high cost of equipment. Nevertheless, these techniques are gradually entering the operating theatre and contribute to the monitoring of the anaesthetized patient. EEG, in particular, regardless of the method of analysis used, seems effective and reliable during the induction phase of anaesthesia, However, the most adequate method of monitoring the maintenance phase or detecting awareness during anaesthesia remains to be produced. PMID- 7872535 TI - [Recovery after anesthesia with Diprivan]. AB - In view of the rapid and complete recovery, the low incidence of hangover, nausea or vomiting, propofol can be considered as first choice agent for minor surgery, short operations and/or day-case surgery. For long and major procedures it is of no advantage over the thiopental-isoflurane technique. For a rapid recovery, the dose should be titrated, particularly during the closing stage of the procedure. As propofol has some amnesic properties, any instructions given to the patient postoperatively should be in writing. Sexual thoughts resulting from disinhibition may occur during emergence; therefore, it is recommended to have a third party present to avoid any implications of misconduct. PMID- 7872536 TI - [Modes of administration of Diprivan]. AB - Administration of propofol using standard syringe pumps has become routine in anaesthesia. The marketing of syringe pumps adapter for anaesthesia (high flow rate enabling a bolus injection and a slower rate for maintenance), allows an easier setting up of total intravenous anaesthesia. Computer-aided infusion of propofol will undoubtedly expand in the near future, as a result of the forthcoming marketing of computer-controlled infusion pumps and of improvement in the recognition of accurate individual pharmacokinetic parameters. This computer aided infusion will be based on a blood concentration criterion, and no longer on a dosage regimen given to the patient. A closed loop regulatory system remains in the domain of research. PMID- 7872537 TI - [Use of Diprivan in ENT and stomatology]. AB - Irrespective of the type of surgery, patient monitoring, including ECG-automated non-invasive blood pressure measurements, SpO2, FIO2 and capnography, is compulsory. Sedation: no initial bolus injection of propofol; continuous infusion of propofol at a rate of 1 to 4 mg.kg-1.h-1, using a syringe pump, combined with a short-acting opioid such as alfentanil. General anaesthesia: initial bolus injection of propofol between 2 and 3.5 mg.kg-1, combined with 10 mg of lidocaine in the same syringe; maintenance with a syringe pump: 6 to 9 mg.kg-1.h-1 combined with an opioid, with or without coadministration of muscle relaxants. Intubation avoiding respiratory depression: syringe pump with a fast infusion rate (50 to 100 mg.min-1), which allows induction with propofol and intubation without co administration of muscle relaxants. PMID- 7872538 TI - [Use of Diprivan in ophthalmology]. AB - Propofol may be used in several ways: As an induction agent for general anaesthesia. Maintenance is ensured by a halogenated anaesthetic, an opioid and a muscle relaxant, in an intubated and ventilated patient. It is interesting to administer propofol simply for induction, because of the rapid recovery. As the main anaesthetic agent, ensuring induction and maintenance of anaesthesia, combined with an opioid and a muscle relaxant, particularly during total intravenous anaesthesia. The patient is intubated and ventilated mechanically. To complement retrobulbar or peribulbar anaesthesia, given just before administration of the local anaesthetic, to produce amnesia of the injection. Small doses of propofol are then sufficient (0.3 to 1.5 mg.kg-1). Some authors continue to administer propofol throughout the procedure, with the patient breathing spontaneously. In young adults, a dosage regimen of 2.5 mg.kg-1 for induction, followed by an infusion or preferably a syringe pump administration of 6 to 12 mg-1.kg-1, ensures calm induction and rapid recovery. A gradual decrease in the administration rate: 10 mg.kg-1.h-1 for 10 min. 8 mg.kg-1.h-1 for 10 min, then 6 mg.kg-1.h-1, has been suggested. In the elderly, over 60 years of age, reducing the dose of propofol by 50% limits haemodynamic effects. Prior vascular fluid loading with 5 to 10mL.kg-1 is preferred by some authors. Administration of 0.5 to 1.5 mg.kg-1 by slow injection or titration, while monitoring haemodynamic effects, decreases side effects. Maintenance of anaesthesia with a dose range of 3 to 9 mg.kg-1.h-1 of propofol, according to surgical stimuli and haemodynamic stability, is recommended. In children between 3 and 10 years of age, larger doses are required, over 3 mg.kg-1 in 20 seconds, virtually without excitatory phenomena. In the absence of premedication, a dose of 4 mg.kg-1 is recommended.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872539 TI - [Use of Diprivan in neurosurgery]. AB - Propofol is an appropriate agent in neurosurgery, where it represents an alternative to the thiopentone-isoflurane anaesthetic technique. Some patients are at risk of hypotension during induction of anaesthesia which may be associated with an important decrease in cerebral perfusion pressure. The administration of propofol as a continuous infusion is therefore preferable in these patients. In the absence of nitrous oxide, propofol anaesthesia allows the monitoring of sensory evoked potentials during spinal surgery. For surgery of epilepsy, it is preferable to avoid giving propofol in the minutes preceding the electroencephalographic location of the areas to be excised. PMID- 7872540 TI - [Use of Diprivan in burn patients]. AB - The use of propofol should be avoided in the first 48 hours after a burn injury, as a major haemodynamic instability characterizes this period. For excision and/or grafting, propofol is mainly used as an induction agent. Maintenance of anaesthesia requires higher doses, often in the range of 15 mg.kg-1.h-1, and varying with each patient and the stage of the burn. Propofol is most appropriate in anaesthesia for dressing changes, considering the repetition of the procedures, interfering least with enteral nutrition and the quality of recovery, considered as essential. Combined with alfentanil or fentanyl, the dose of propofol is titrated to obtain the desired effect, from a simple sedation with patient co-operation to total anaesthesia. PMID- 7872541 TI - [Diprivan and electroconvulsive therapy]. AB - Anaesthesia for Electroconvulsive Therapy (ECT) is characterized by short repeat anaesthetic procedures, performed outside an operating theatre. The efficacy of ECT relies upon the occurrence of tonoclonic convulsions. Propofol seems to be the intravenous induction agent of choice for ECT. Its pharmacokinetic properties ensure a rapid and deep anaesthesia, of short duration, with a minimum of side effects, and a rapid recovery of good quality, suitable for short repetitive procedures. As low doses of propofol are used, a rapid injection is required to obtain the hypnotic effect. These low doses also have the advantage of not affecting the convulsion threshold and therefore the efficacy of ECT. Clear upper airways and prevention of tongue biting are ensured by inserting a Guedel airway after loss of consciousness and before the electric shock. Intravenous administration of 10-20 micrograms.kg-1 atropine prevents from bradycardia, related to initial vagal stimulation induced by the electric shock. Its action is potentiated by the anticholinergic effect of tricyclic antidepressants. Its use is also justified when suxamethonium is given to prevent patient's movements and possible ECT-related trauma. Only suxamethonium is suitable for these procedures because of its pharmacokinetic properties (rapid onset and short duration of action). The suggested doses for this indication range from 0.5 to 1 mg.kg-1. When contraindicated, suxamethonium may be replaced by a benzodiazepine, in order to achieve an acceptable degree of muscle relaxation. There may then be an effect on the convulsion threshold. PMID- 7872542 TI - [Use of Diprivan in laparoscopic surgery]. AB - Anaesthesia is induced, as usual, after inhalation of oxygen at 100 vol p. 100, with propofol 2-2.5 mg.kg-1 associated with a muscle relaxant for tracheal intubation. The inhalation of oxygen is maintained as long as the spontaneous ventilation is persisting. The trachea is intubated following the occurrence of apnoea. Anaesthesia is maintained with a continuous infusion of propofol at a low rate of about 4-8 mg.kg-1.h-1. At this rate the arterial pressure remains very stable during the whole course of the procedure. The infusion rate depends also on the dose and the type of the associated analgesic agent. Analgesia can be obtained either with alfentanil 30 micrograms.kg-1.h-1 or with fentanyl 1.5 micrograms.kg-1, administered about every 30 min. Muscle relaxation should remain stable until the end of the main surgical period. Nitrous oxide does not seem to interfere with surgery. Its involvement in the occurrence of postoperative nausea and vomiting has not been proven. Atropine (0.02 mg.kg-1, possibly repeated) should be administered as soon as the heart rate decreases below 50 b.min-1. When a gradual postanaesthetic recovery is desirable, the infusion rate of propofol is progressively decreased (decrease of about 2 mg.kg-1.h-1 every 20-30 min, according to the FETCO2 and the temperature). PMID- 7872543 TI - [Diprivan: effects on heart and vessels]. PMID- 7872544 TI - [Cardiovascular effects of Diprivan]. AB - Propofol is a greater cardiovascular depressant agent than barbiturates (thiopentone, methohexitone). It is agreed that propofol changes the ventricular load as a result of its vasodilating effects, and that it depresses the sympathetic nervous system and the baroreflex, which result in a moderate bradycardia. The direct effects of propofol on the myocardium remain controversial. Propofol has no significant direct effect on intrinsic myocardial contractility and the decrease in cardiac output is related to anaesthesia on the one hand and to changes in ventricular load and the activity of the cardiac autonomic nervous system on the other hand. It is therefore understandable that the overall depressant effect of the cardiovascular system is amplified in patients whose ventricular function is closely dependent upon ventricular load and/or the activity of the sympathetic nervous system, and that the association with drugs causing bradycardia must be avoided. The logical therapeutic solution to propofol related cardiovascular depression, when deemed necessary, consists of vascular fluid loading and/or the administration of a vasoconstrictor. PMID- 7872545 TI - [Coronary patient undergoing non cardiac surgery and Diprivan]. AB - It is legitimate to avoid the administration of propofol in patients suffering from severe ischaemic heart disease (unstable angina). Propofol may be given to patients with stable angina. However, to avoid hypotension, which may compromise oxygen delivery to areas of myocardium supplied by stenosed arteries, it is essential to treat any possible hypovolaemia and to administer fentanyl before tracheal intubation, in order to reduce the dose of propofol. PMID- 7872546 TI - [Diprivan and cardiac surgery]. AB - Owing to its haemodynamic properties, it would not be advisable to use propofol for the induction of anaesthesia in patients undergoing an aorto-coronary bypass graft surgery and/or valve replacement. Its use as a continuous infusion, started after induction, is deemed possible since it avoids episodes of awareness, without inducing significant haemodynamic changes, especially when weaning from cardiopulmonary bypass. If early extubation is indicated, propofol could be used for heart surgery. PMID- 7872547 TI - [Use of Diprivan in the elderly]. AB - Propofol may be safely used in elderly patients provided that: hypovolaemia is corrected prior to procedure; a decrease in blood pressure of more than 25 per cent of the baseline value is treated with a sympathomimetic drug (e.g. ephedrine); bradycardia below 55 b.min-1 using atropine; not more than 5 mL (50 mg) of propofol are injected per minute; the induction dose does not exceed 1.5 mg.kg-1, with a possible further dose of 0.2 to 0.4 mg.kg-1, immediately prior to intubation; opioids are not administered before stabilization of blood pressure during the period proceeding intubation; nitrous oxide and halogenated anaesthetics are not used as long as haemodynamic parameters are unstable; the dose of beta-blockers, ACE inhibitors and calcium antagonists is decreased or the drugs discontinued prior to surgery, depending upon their effect and their duration of action, except in cases of unstable angina or severe hypertension. PMID- 7872548 TI - [Use of Diprivan in cardioversion and interventional cardiology]. AB - Propofol ensures a calm and rapid induction of anaesthesia in case of planned cardioversion for supraventricular arrhythmia. An appropriate level of anaesthesia is obtained with a dose of 1.4 to 2 mg.kg-1. Propofol does not affect the success rate of cardioversion. However, given as a bolus injection, it causes a more pronounced decrease in blood pressure than other induction agents and the rate of apnoea is higher. The incidence of these adverse effects may be reduced by slowly titrating the dose. The frequent association with cardiac disease, in particular valvular disease or coronary insufficiency, should be taken into account and may represent a contra-indication for the administration of propofol. Furthermore, administration of this agent is not indicated if the arrhythmia is poorly tolerated, because of the risk of increasing hypotension. The known advantages of propofol on recovery have no significant role in this indication. PMID- 7872549 TI - [Diprivan: ambulatory surgery and anesthesia outside the operating room]. PMID- 7872550 TI - [Effects of Diprivan on nausea and vomiting]. AB - Total intravenous anaesthesia using propofol is indicated in the following cases: patients with a previous history of postoperative nausea or vomiting; surgery of the middle ear; gynaecological procedures involving laparotomy; ENT and squint surgery in children. Up to now, the relationship between the clinical benefit (less incidence of postoperative nausea and vomiting) and intrinsec anti-emetic properties of propofol is not included in the regulatory labelling. PMID- 7872551 TI - [Use of Diprivan for digestive system endoscopy]. AB - After evaluation of the patient's clinical condition and appropriate premedication is seems reasonable to suggest for: 1. Endoscopic procedures involving the gastro-intestinal tract: slow, titrated induction, using 0.5 to 1 mg.kg-1 of propofol, until the required level of sedation has been achieved; this may or not be preceded by the injection of a low dose of midazolam (0.02 to 0.03 mg.kg-1) or of alfentanil (5 micrograms.kg-1); maintenance is achieved by bolus injections of 20 mg (up to 0.5 mg.kg-1); maintenance of spontaneous ventilation, with oxygen administration is the rule; SpO2 is monitored routinely; anaesthesia has to be performed according to the recommendations of the French Society of Anaesthesia and Intensive Care (SFAR) and the anaesthetist must be prepared to manage any incident during the endoscopy and the recovery period. 2. Procedures involving the biliary tract and the oesophagus, which require deeper anaesthesia: induction should again be titrated using a very slow infusion, with doses ranging from 0.9 to 2.2 mg.kg-1); the maintenance requires a continuous infusion, doses ranging from 4 to 6 mg.kg-1.h-1 when propofol is administered alone and from 4 to 12 mg.kg-1.h-1 when combined with an opioid; continuous oxygenation is necessary using a nasal airway; the need for intubation depends on the type of procedure and the status of the patient; the same monitoring devices and similar safety measures are required during and after procedure as for any anaesthetic or sedation, especially when it is performed in day-case patients or outside the operating theatre. PMID- 7872552 TI - [Use of Diprivan in ambulatory plastic surgery]. AB - Numerous techniques have been proposed for use in day-case plastic surgery. Propofol combined with alfentanil bolus injections, or with local or regional anaesthesia appear to be the two most suited techniques for this type of procedure. One variation of it is becoming increasingly common: office surgery. It must be emphasized that, under these conditions, the greatest care should be taken in providing anaesthesia. Propofol has been granted a marketing licence with the following precautions: "The use of this product is restricted to anaesthetists working in private or public hospitals fully equipped with the respiratory and resuscitation equipment required for any procedure under general anaesthesia". Its use for office surgery is therefore not included in the marketing licence. Propofol's ease of use should not serve as a pretext to reduce indispensable safety measures required for anaesthesia. The rapid elimination of currently available agents, such as propofol, should lead neither to a reduction of postoperative monitoring nor to the application of less rigorous discharge criteria. These comments should be particularly taken into consideration in case of plastic surgery, where good results and not only the adequacy of the means employed are essential. PMID- 7872553 TI - [Use of Diprivan in radiology]. AB - For radiological examinations, propofol is administered, depending on the indications, at following doses: for anxiolysis: i.v. bolus of 10-20 mg, repeated as required; for sedation with maintenance of spontaneous ventilation: i.v. bolus of 0.5 mg.kg-1 or continuous infusion of 3 mg.kg.h-1. for general anaesthesia: i.v. bolus of 2 mg.kg-1 and maintenance with a continuous infusion of 6-10 mg.kg 1.h-1. These doses are modified according to the patient's reactions and painful episodes. In neuroradiology, indications for anaesthesia include vascular explorations, MRI, computerized axial tomography, as well as biopsies of organs and tumors, with the exception of explorations in patients with tight stenoses of the carotid artery. The use of propofol for cardiological explorations is questioned in adults and mainly in children with a congenital cardiopathy. For some authors this agent is contra-indicated, as during induction it decreases, sometimes excessively, the mean arterial pressure. PMID- 7872554 TI - [Use of Diprivan in addition to locoregional anesthesia]. AB - During regional anaesthesia, sedation can be used to obviate any discomfort which is unrelated to a technical insufficiency of the block or a particular anxiety of the patient. Sedation increases the acceptability of the technique by the patient. The main characteristics of propofol are its short onset time of action, and the rapid reversibility of its effects after the end of its administration. For induction of anaesthesia, propofol is given as a bolus injection, an average dose being 10 to 20 mg. Maintenance is best achieved with a continuous infusion, at a rate of 3 to 4 mg.kg-1.h-1. Titration of propofol allows the ideal stage of sedation to be reached (MacKenzie Grade 3), followed by a fast recovery. Close monitoring of the patient is mandatory and should include clinical supervision and pulse oximetry in all cases. PMID- 7872555 TI - [Diprivan and ventilation]. PMID- 7872556 TI - [Diprivan: intubation without curare]. AB - To intubate under ideal conditions, i.e. with the vocal cords abducted and no motor response to the insertion of the endotracheal tube, the anaesthetist has two alternatives: to use muscle relaxants or to anaesthetize the patient deeply. Apart from cases where muscle relaxants are contra-indicated or required by the type of procedure: Intubation using muscle relaxants means: maintaining the option of varying the depth of anaesthesia, while keeping optimal conditions for intubation; reducing the risk of airways trauma. Intubation without muscle relaxants means: avoiding the risk of allergic complications; producing deep anaesthesia and controlling any resulting haemodynamic effects. The recommended induction agent is propofol, given as a bolus injection at a dose equal to or greater than 2.5 mg.kg-1 in adults and 3.5 mg.kg-1 in children. Alfentanil is the opioid of choice, the dose being between 30 and 40 micrograms.kg-1. Lidocaine, injected as premedication at a dose of 1.5 mg.kg-1 potentiates the effect of alfentanil. The order of injection of the induction agents is important, as it determines the exact moment for laryngoscopy and intubation. PMID- 7872557 TI - [Diprivan: sedation for difficult intubation]. AB - No study has compared anaesthetic protocols appropriate for the sedation for fiberoptic tracheal intubation. Extrapolation of results of randomised studies comparing sedation techniques for diagnostic bronchoscopy under local anaesthesia enables the following conclusions: 1. Possible hypnotic agents for this procedure are benzodiazepines, barbiturates and propofol. Fentanyl improves the conditions for bronchoscopy. 2. Sedation using propofol is a well established technique. The induction dose, given as a bolus injection is 1 mg.kg-1, followed by continuous maintenance infusion of 1 mg.kg.h-1. 3. Irrespective of the sedation protocol used, there is always respiratory depression which justifies the need for preoxygenation, continuous oxygenation and Spo2 monitoring. Reversal of benzodiazepine and opioid effects may temporarily protect against respiratory depression. PMID- 7872558 TI - [Diprivan and full stomach]. AB - On the basis of published data and our own experience, the procedure to be followed for general anaesthesia in a patient with a full stomach is that of a rapid sequence induction (induction-intubation) or "crash-induction". This technique which consists of the administration of atropine, a hypnotic and suxamethonium together with Sellick's manoeuvre, will provide the best conditions for intubation. In view of the characteristics of propofol (rapid effect, deep depression of pharyngo-laryngeal reflexes) it seems possible to use it as a first choice induction agent in patients who are haemodynamically stable. However, it should be noted, that there is, as yet, no evidence of the superiority of propofol over other induction agents. PMID- 7872559 TI - [Diprivan and ventilation: laryngeal mask]. AB - The laryngeal mask ensures a better control of the airway than the face mask, without the disadvantages of an endotracheal tube. Moreover, it provides an effective and simple solution to many problems of difficult intubation and therefore it has a place amongst the equipment required for difficult intubations. The laryngeal mask will most probably become more widely used, provided that its contra-indications are taken into account. These are dominated by its inability to protect the airway from inhalation of gastric contents in patients with a full stomach. Many studies have shown that propofol is suitable for use with the laryngeal mask. However, it should be noted, that there is, as yet, no conclusive evidence of the superiority of propofol over other induction agents. In anaesthesia for day-case surgery, the combination of the laryngeal mask and propofol could prove beneficial. PMID- 7872560 TI - [Use of Diprivan in chronic respiratory insufficiency]. AB - Propofol may be recommended as an anaesthetic agent in patients with chronic respiratory insufficiency since: it prevents the increase in bronchial resistances resulting from the administration of opioids; it possesses a bronchodilator effect, comparable with that of flunitrazepam; it ensures rapid recovery, which would favour patient's co-operation postoperatively. The effects of propofol on respiratory drive should not be neglected, as they may persist even after complete recovery. In pulmonary surgery, propofol may be recommended in patients with one-lung ventilation, since it does not depress the hypoxic vasoconstriction reflex. Some procedures may be carried out in spontaneous ventilation or, preferably, using jet ventilation, provided that propofol is given by means of an infusion pump. PMID- 7872561 TI - [Diprivan and asthma]. AB - Propofol is probably a safe agent in asthmatic patients. In clinical practice, its efficacy in reducing the incidence of peroperative bronchospasm is deemed possible, but has not yet been totally established. With respect to the regression of bronchospasm in a patient receiving propofol, it is not possible to accurately differentiate between the beneficial effects related to the depth of anaesthesia and a specific effect of this agent on bronchial tone. Finally, its haemodynamic effects in case of severe bronchospasm remain to be assessed. PMID- 7872562 TI - [Diprivan and locoregional anesthesia in children over 3 years of age]. AB - Preparation for anaesthesia (at least 1 hour prior to surgery): Topical anaesthesia at venepuncture sites and at the site of the block. Possible premedication (rectal midazolam: 0.3 mg.kg-1). Anaesthetic induction: Insertion of venous cannula; i.v. injection of 3-4 mg.kg-1 propofol, mixed with 0.05% lidocaine; Control of child's ventilation conditions: tolerance of the face mask, Guedel airway, laryngeal mask; tracheal intubation would be easy if necessary and would not require muscle relaxants; In cases where the child is distressed or where venous access cannot be obtained, it is sometimes preferable to resort to inhalational induction with halogenated anaesthetics prior to venepuncture. Initial maintenance anaesthesia (performing the block): Propofol given as a continuous infusion of 13 mg.kg-1.h-1, after a bolus injection of 1.3 mg.kg-1 (alternative solution: maintaining anaesthesia using halogenated agents); Positioning of the patient and performing the block technique with relatively concentrated local anaesthetic solutions (to avoid differential blocks). Maintenance anaesthesia during the procedure: Propofol given as a continuous infusion in reduced doses: 2 to 5 mg.kg-1.h-1; Alternatively: halogenated anaesthesia at low concentrations (equivalent to 0.25 to 0.5 vol % of halothane). Recovery: Particularly rapid and pleasant recovery, with a minimum of side effects; In cases of day-case surgery, patient discharge has virtually never to be postponed. PMID- 7872563 TI - [Use of Diprivan in obstetrics]. PMID- 7872564 TI - [Use of Diprivan in gynecology]. AB - 1. Propofol as an induction agent At a dose of 2 to 2.5 mg.kg-1, as a bolus injection over 30 to 60 seconds, for gynaecological procedures of short duration (abortion, D and C), propofol can be characterized as follows when compared with other induction agents: ADVANTAGES OVER METHOHEXITONE AND ETOMIDATE: decreased incidence of hiccups and abnormal movements, increased quality of induction, similar to that obtained with thiopentone, decreased postoperative nausea and vomiting. ADVANTAGES OVER THIOPENTONE: shorter recovery period, more rapid recovery of consciousness and orientation. DISADVANTAGES WHEN COMPARED WITH THIOPENTONE: more frequent pain at the injection site, however its prevention is possible, more frequent apnoea, but may be avoided by slowly injecting the drug, higher cost. The main advantage of propofol over thiopentone (shorter recovery period), makes day-case gynaecological procedures one of its major indications. This concerns young, healthy women, whose professional and family lives are important and who may benefit from minimal disruption in their way of life. 2. Propofol as a maintenance agent Propofol is given as a continuous infusion at a dose ranging from 6 to 12 mg.kg-1.h-1 for maintenance of prolonged procedures (abdominal surgery, hysterectomy) and can be characterized as follows with respect to halogenated anaesthetics: ADVANTAGES OVER ENFLURANE AND ISOFLURANE: decreased postoperative nausea and vomiting, increased recovery scores (1st hour). COMPARED WITH DESFLURANE: shorter induction time than desflurane, less respiratory problems at induction, similar recovery period, same incidence of nausea and vomiting. The administration of propofol for maintenance of anaesthesia has the main advantage of reducing the incidence of postoperative nausea and vomiting when compared to conventional halogenated anaesthetics. Respective costs of the various techniques, using propofol or the new halogenated anaesthetics, may be a criterion for choice in the future.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872565 TI - [Diprivan in children under 3 years of age]. AB - Today, the lack of the marketing licence for administration of propofol for anaesthesia in children of less than three years does not allow to recommend the administration of propofol for that indication. Its use for sedation in children under fifteen is contra-indicated. PMID- 7872566 TI - [Use of Diprivan for prehospital emergencies]. AB - The use of propofol at the scene of an accident or during transport to the hospital: 1. Should be restricted to fully qualified anaesthetists of an Emergency Mobile Hospital Unit. 2. Is probably rather limited, as: the indications for anaesthesia in this context are relatively rare; they are dominated by trauma cases (which represent 20 to 30 per cent of the activity of an Emergency Mobile Hospital Unit) and other accident-related conditions; furthermore, in most emergency situations, sedation and/or analgesia of varying depth are more often required; the indications for propofol would be rare because of: its haemodynamic effects, especially as hypovolaemia is extremely frequent, as neurological damage is often existing, and the medical history of the patient is frequently unknown; the possible choice of other agents, such as midazolam, which is widely used as well as etomidate or ketamine; 3. Should follow the same guidelines as those in use for its intra-hospital administration: propofol is undoubtedly a valuable agent as it allows a rapid induction, depresses the pharyngo-laryngeal reflexes, and has the advantage of producing a rapid, good quality recovery which provides an important element of safety; however, for as long as prospective comparative studies have not specifically been carried out in the area of pre-hospital anaesthesia, the greatest circumspection is required. Any contraindication and precaution recommended from hospital use should be strictly adhered to and amplified because of the difficult circumstances and the other available alternatives kept in mind. PMID- 7872567 TI - [36th National Congress of Anesthesia-Resuscitation. 30 September-2 October 1994. Abstracts]. PMID- 7872569 TI - The dynamics of sustained reentry in a ring model of cardiac tissue. AB - This paper describes the dynamics of circus movement around a fixed obstacle, using a one-dimensional continuous and uniform ring model of cardiac tissue to simulate sustained reentry. The membrane ionic current is simulated by a modified Beeler-Reuter formulation in which the kinetics of the fast sodium current were updated using more recent voltage-clamp data. Changes in the ring length are used to modify the dynamics of reentry. Reentry is stable if the ring length (X) exceeds a critical value (Xcrit) and complete block occurs if X is below a minimum (Xmin). Irregular sustained reentry is observed at intermediate ring lengths, as a narrow range of aperiodic reentry near Xcrit, and a larger range of quasi-periodic reentry at shorter ring lengths. The basic pattern of irregular reentry is an alternation between long and short cycle length, action potential duration (APD), diastolic interval (DIA), wavelength, and excitable gap. In aperiodic reentry cycle length variations are small, APD and DIA fluctuations are of medium amplitude, and conduction velocity over the whole pathway is essentially constant during successive turns. Much larger fluctuations in these various quantities occur during quasi-periodic reentry, and they increase in size as X approaches Xmin. The complexity of quasi-periodic reentry patterns is related to three factors: the slope of the APD versus DIA relation, which is greater than 1, the existence of a zone of slow conduction on the ring when the excitable gap becomes quite short, and the occurrence of triggered waves of secondary repolarization and excitability recovery. In the present model, quasi periodic reentry with triggered secondary recovery covers most of the range of ring lengths, giving rise to sustained irregular reentry. There is very close agreement between our simulation results and experimental data obtained on rings of cardiac tissue. PMID- 7872568 TI - Contractile-based model interpretation of pressure-volume dynamics in the constantly activated (Ba2+) isolated heart. AB - A contractile-based model was constructed to represent responses to changes in left ventricular (LV) volume in a heart with constantly activated myocardium. Hearts were isolated from rabbits, the myocardium was put into a state of constant activation by perfusion with Krebs Henseleit solution containing 0.5 mM Ba2+, and recordings were taken of LV pressure responses to step and sinusoidal changes in LV volume. Pressure responses to volume steps were divided into five characteristic phases. An elastance frequency spectrum was calculated from pressure responses to sinusoidal volume changes. Values of features of the elastance frequency spectrum were in accord with values of corresponding features of the step response. Using an explicit homology between elements responsible for LV pressure development (pressure generators) and elements responsible for muscle force development (myofilament cross-bridges), mathematical models were constructed to re-create the data. Basic assumptions were that (1) pressure was the summed effect of pressure generators undergoing volumetric distortion; (2) changes in volume brought about changes in both generator numbers (recruitment) and generator distortion; (3) pressure generators cycle through states that variously do and do not generate pressure. An initial two-step model included a cycle with one attachment step and one detachment step between non-pressure bearing and pressure-bearing states. Predictions by the two-step model had many similarities with the experimental observations, but were lacking in some important respects. The two-step model was upgraded to a multiple-step model. In addition to multiple attachment and detachment steps within the cycle, the multiple-step model incorporated distortion-dependent detachment steps. The multiple-step model re-created all aspects of the experimentally observed step and frequency responses. Furthermore, this model was consistent with current theories of contractile processes. PMID- 7872570 TI - Simulation of two-dimensional anisotropic cardiac reentry: effects of the wavelength on the reentry characteristics. AB - A two-dimensional sheet model was used to study the dynamics of reentry around a zone of functional block. The sheet is a set of parallel, continuous, and uniform cables, transversely interconnected by a brick-wall arrangement of fixed resistors. In accord with experimental observations on cardiac tissue, longitudinal propagation is continuous, whereas transverse propagation exhibits discontinuous features. The width and length of the sheet are 1.5 and 5 cm, respectively, and the anisotropy ratio is fixed at approximately 4:1. The membrane model is a modified Beeler-Reuter formulation incorporating faster sodium current dynamics. We fixed the basic wavelength and action potential duration of the propagating impulse by dividing the time constants of the secondary inward current by an integer K. Reentry was initiated by a standard cross-shock protocol, and the rotating activity appeared as curling patterns around the point of junction (the q-point) of the activation (A) and recovery (R) fronts. The curling R front always precedes the A front and is separated from it by the excitable gap. In addition, the R front is occasionally shifted abruptly through a merging with a slow-moving triggered secondary recovery front that is dissociated from the A front and q-point. Sustained irregular reentry associated with substantial excitable gap variations was simulated with short wavelengths (K = 8 and K = 4). Unsustained reentry was obtained with a longer wavelength (K = 2), leading to a breakup of the q-point locus and the triggering of new activation fronts. PMID- 7872571 TI - A computer model study of the ventricular fibrillation vulnerable window: sensitivity to regional conduction depressions. AB - The cardiac vulnerable window is typically defined to be that portion of the cardiac cycle during which ectopic stimuli can induce ventricular fibrillation (VF). We have used cardiac electrophysiological computer modeling to investigate how the size and shape of the cardiac vulnerable window is affected by regional conduction velocity depressions (RCVDs), as might be found in ischemia. Computer simulations were performed on a three-dimensional finite-state, discrete-element model of the ventricles of a dog heart, with simulated RCVDs of 0% (normal) to 100% (infarcted) isolated to the apical region of this heart. Using a programmed electrical stimulation protocol, vulnerability was quantified as the number of ectopic stimuli necessary to induce VF. We observed a nonlinear and nonmonotonic relation between increases in RCVD and the vulnerability of the heart to ectopic stimuli. The size and shape of the vulnerable window remained stable through RCVDs of 30%, expanded rapidly thereafter through RCVDs of 90%, and then contracted significantly at the RCVD of 100%. These increases in vulnerability were manifest as both a lowering of the overall stimulus thresholds necessary for fibrillation (window "deepening"), and an increase in the fraction of the cardiac cycle susceptible to these ectopic stimuli (window "widening"). In all cases of induced VF, the mechanism of induction was through reentry facilitated by temporary functional block. Moreover, the ability to form such a block--and thus the likelihood of subsequent VF--was enhanced as the RCVD increased. Taken together, these results demonstrate the complex relation between vulnerability and RCVD and, at the very least, suggest that the entire shape of the vulnerable window, rather than just its minimum threshold, is important when determining a heart's electrical stability. These conclusions are supported by results obtained from an experimental study--which utilized a similar programmed stimulation protocol--of normal and ischemic canine hearts. PMID- 7872572 TI - Parameter identification in coronary pressure flow models: a graphical approach. AB - The confident identification of parameters is important in the practical application of physiological models. However, the task of parameter identification is often complicated by interactions among parameters and by the fact that the sensitivity of the model to changes in a given parameter is generally a function of all the other parameters. Here we illustrate a graphical approach to parameter identification that allows the modeler to visualize the behavior of the model, the sensitivity functions, and certain functions characteristic of parameter interdependence. The visual display can be generated over any desired portion of parameter space. The technique is applied to a simple, four-parameter, myocardial pump model of the coronary circulation. The results indicate that over specified ranges of parameters, it is possible to distinguish among the four parameters of the model: the ratio of proximal-to distal resistance, alpha; the overall resistance of the vascular bed, R; the compliance of the vascular bed, C; and a parameter, kappa, relating tissue pressure to left ventricular pressure. It was found that in order to identify all parameters uniquely, it was necessary to regress upon both coronary inflow and outflow. PMID- 7872573 TI - Effects of myocardial contraction on coronary blood flow: an integrated model. AB - The effects of myocardial contraction on the coronary flow are studied by means of an integrated structural model of left ventricular (LV) mechanics, coronary flow, and fluid and mass transport. This model relates global LV performance, and in particular coronary flow dynamics, to myocardial composition and structure and contractile sarcomere activity. Extravascular pressure is identified with hydrostatic tissue pressure, i.e., intramyocardial pressure (IMP), and is determined by the dynamics of myocardial contraction and fluid transport. Consistent with available experimental data, changes in myocardial function and contractile state are simulated by changing the sarcomere contractile properties or changing the LV loading conditions. The model's predictions are successfully compared with a wide range of experimental studies; all but one were performed at a constant coronary perfusion pressure and maximal vasodilation. The results indicate a dominant effect of the myocardial contractile state on coronary flow and a dissociation between coronary compression and LV cavity pressure (LVP) when the pressure is controlled by load changes. However, when active sarcomere contraction is regionally impaired by lidocaine, LVP plays an important role in the coronary flow characteristics. The model adequately predicts observations on the effect of cardiac contraction on systolic and diastolic coronary flows, as well as the role of LVP at different loading and contractile conditions. The analysis supports the hypothesis that coronary compression, as mediated through IMP, is independent of LV loading conditions and depends on myocardial contractility and coronary perfusion pressure. PMID- 7872574 TI - Optical measurements of lung microvascular filtration coefficient using polysulfone fibers. AB - Lung fluid balance, which is governed by the product of net transvascular pressure difference and lung filtration coefficient, can be altered in pulmonary diseases. A simple measurement of the lung filtration coefficient (Kfc) would be clinically useful and has been examined by several researchers. Current methods of determining Kfc include gravimetric measurement in isolated lungs and lymph node cannulation, neither of which can be extended to human use. Optical measurements of protein concentration changes in venous blood can be combined with pressure measurements to calculate Kfc. Blood, though, contains red corpuscles, which tend to absorb and scatter light, obscuring these optical measurements. In this study, an optical system was developed in which a polysulfone filter cartridge was used to remove red blood cells before the filtrate was passed through a spectrophotometer. Absorbance changes caused by changes in concentration of albumin labeled with Evans Blue were monitored at 620 nm after venous pressure was elevated by about 13 cm H2O. Optical measurements of Kfc averaged 0.401 +/- 0.074 (ml/min cm H2O 100 g DLW) for an isolated canine lung. Optical measurements of Kfc (0.363 +/- 0.120 ml/min cm H2O 100 g DLW) were made for the first time in an intact, closed chest sheep in which pulmonary pressure was altered by inflating a Foley balloon in the left atrium. We conclude that absorbance and scattering artifacts introduced by red blood cells can be eliminated by first filtering the blood through polysulfone fibers. Kfc measurements using the optical method are similar to values obtained by others using gravimetric methods. Finally, we have demonstrated that the technique can be used to estimate Kfc in an intact animal. PMID- 7872575 TI - Lung tissue rheology and 1/f noise. AB - The mechanical properties of lung tissue are important contributors to both the elastic and dissipative properties of the entire organ at normal breathing frequencies. A number of detailed studies have shown that the stress adaptation in the tissue of the lung following a step change in volume is very accurately described by the function t-k, for some small positive constant k. We applied step increases in length to lung parenchymal strips and found the ensuing stress recovery to be extremely accurately described by t-k over almost 3 decades of time, despite the quasi-static stress-length characteristics of the strips being highly nonlinear. The corresponding complex impedance of lung tissue was found to have a magnitude that varied inversely with frequency. We note that this is highly reminiscent of a phenomenon known as 1/f noise, which has been shown to occur ubiquitously throughout the natural world. 1/f noise has been postulated to be a reflection of the complexity of the system that produces it, something like a central limit theorem for dynamic systems. We have therefore developed the hypothesis that the t-k nature of lung tissue stress adaptation follows from the fact that lung tissue itself is composed of innumerable components that interact in an extremely rich and varied manner. Thus, although the constant k is no doubt determined by the particular constituents of the tissue, we postulate that the actual functional form of the stress adaptation is not. PMID- 7872576 TI - Role of the tendon in the dynamic performance of three different load-moving muscles. AB - The effect of the tendon's viscoelastic properties on the dynamic performance of three different load-moving muscles was determined. The frequency response models of the cat's medial gastrocnemius (MG), extensor digitorum longus (EDL), and tibialis anterior (TA) with and without their tendons were derived under sinusoidal shortening-lengthening, manipulated by orderly recruitment and derecruitment of motor units together with firing rate increase and decrease. The passive load sizes applied to the muscles were approximately 30%-40% of each muscle's maximal isometric force. It was shown that the tendon has a moderate effect on the dynamic response of muscles while moving loads of fixed mass. The MG and EDL without their tendons show a decrease in high frequency gain (2-5 dB) and increasing phase lag angles (7 degrees-9 degrees). In contrast, the TA without its tendon shows an increase in high frequency gain (2 dB) and decreasing phase lag angles (20 degrees) compared with the same muscle with the tendon. It was concluded that tendon's viscoelastic properties have a moderate effect during load-moving contractions, influencing the dynamic performance of different muscles in a different manner. PMID- 7872578 TI - Reflections of evolution and culture in children's cognition. Implications for mathematical development and instruction. AB - An evolution-based framework for understanding biological and cultural influences on children's cognitive and academic development is presented. The utility of this framework is illustrated within the mathematical domain and serves as a foundation for examining current approaches to educational reform in the United States. Within this framework, there are two general classes of cognitive ability, biologically primary and biologically secondary. Biologically primary cognitive abilities appear to have evolved largely by means of natural or sexual selection. Biologically secondary cognitive abilities reflect the co-optation of primary abilities for purposes other than the original evolution-based function and appear to develop only in specific cultural contexts. A distinction between these classes of ability has important implications for understanding children's cognitive development and achievement. PMID- 7872577 TI - Inertial properties of the human trunk of males determined from magnetic resonance imaging. AB - The purpose of this study was to evaluate the segmental parameters of the human trunk of males in vivo using magnetic resonance imaging (MRI). In addition, the efficacy of volumetric estimation and existing prediction formulas to produce segmental properties similar to those produced by MRI was evaluated. As opposed to finding one representative normal value for these parameters, a range of normal values was defined. For instance, the average trunk mass was 42.2% +/- 3.5% (x +/- SD) of body mass, but values ranged from 35.8% to 48.0%. To account for segment parameters more accurately, specific anthropometric measures need to be considered in addition to overall measures of body height and mass. These specific measures included segment length, circumference, width, and depth. Studies reporting general percentages based on height and/or mass were found to be inadequate predictors of segmental parameters of the trunk compared with MRI estimates. Volume-based estimates, which assume a uniform density distribution within a segment, were found to correspond closely to MRI values except for the thorax. However, the use of density values reflective of the living in vivo state would likely alleviate this disparity, thus indicating that the volumetric technique may be effective for deriving segmental parameters for large segments of the trunk. Future research should adopt noninvasive techniques such as MRI and/or volumetric estimation to enhance the predictability of segmental parameters of the body for specific population groups characterized by gender, developmental age, body type, and fitness level. Further efforts should be made to establish standardized boundary definitions for trunk segments to avoid unnecessary confusion, from which substantial errors may be introduced into biomechanical linked-segment analyses of human movement. PMID- 7872579 TI - [Use of macroalgae for the evaluation of organic pollution in the Preto river, northwest of Sao Paulo State]. AB - The Preto River, located in the northwest of Sao Paulo State, receives a total wastewater load of 15.150 kg DBO day-1, from which 13.685 kg DBO day-1 (90.5%) corresponds to domestic sewage, and the city of Sao Jose do Rio Preto contributes with 12.400 kg DBO day-1 (90% of domestic sewage). During the period from August 1990 through January 1991, monthly sampling was carried out to evaluate the use of macroalgae as bioindicator of organic pollution. Five sampling sites were established along the main river and the following variables were analised: temperature, conductance, turbidity, dissolved oxygen, BOD, COD, total and fecal coliforms, and composition and abundance of macroalgal communities. Data were submitted to analysis of variance, correlation coefficient, cluster analysis (four different approaches) and converted to biological indices (species deficit, relative pollution, saprobity, diversity and uniformity indices). A wide range in water quality was found (particularly for conductance, oxygen, BOD and COD) among the sampling sites, which were classified into three groups (polluted, moderately polluted and unpolluted/weakly polluted). As regards the occurrence and abundance of macroalgae the Rhodophyta were found only in unpolluted or weakly polluted sites, whereas Cyanophyta occurred mostly under high pollution load; the Chlorophyta species were observed under a wide range of conditions. Among the biological indices, saprobity was the most sensitive and correlated to all water variables and the other indices. Cluster analyses showed that the composition of macroalgal communities was consistent with the levels of organic pollution in the Preto River. PMID- 7872580 TI - Mercury concentrations in fish from the Itacaiunas-Parauapebas River system, Carajas region, Amazon. AB - This paper reports on total Hg concentrations in muscle tissue from 12 fish species collected in the Itacaiunas and Parauapebas Rivers in the Carajas region, South Para. It is found that carnivorous species present Hg concentrations higher than herbivorous and omnivorous species. Also, large carnivorous species presented higher Hg concentrations than smaller carnivorous species. Significant positive relationships are found between fish weight and total Hg concentrations for at least two species studied in detailed, the carnivorous Paulicea lutkeni (jau) and Serrasalmus nattererii (piranha). PMID- 7872581 TI - Weight gain as a risk factor for clinical diabetes mellitus in women. AB - OBJECTIVE: To examine the relation between adult weight change and the risk for clinical diabetes mellitus among middle-aged women. DESIGN: Prospective cohort study with follow-up from 1976 to 1990. SETTING: 11 U.S. states. PARTICIPANTS: 114,281 female registered nurses aged 30 to 55 years who did not have diagnosed diabetes mellitus, coronary heart disease, stroke, or cancer in 1976. OUTCOME MEASURES: Non-insulin-dependent diabetes mellitus. RESULTS: 2204 cases of diabetes were diagnosed during 1.49 million person-years of follow-up. After adjustment for age, body mass index was the dominant predictor of risk for diabetes mellitus. Risk increased with greater body mass index, and even women with average weight (body mass index, 24.0 kg/m2) had an elevated risk. Compared with women with stable weight (those who gained or lost less than 5 kg between age 18 years and 1976) and after adjustment for age and body mass index at age 18 years, the relative risk for diabetes mellitus among women who had a weight gain of 5.0 to 7.9 kg was 1.9 (95% CI, 1.5 to 2.3). The corresponding relative risk for women who gained 8.0 to 10.9 kg was 2.7 (CI, 2.1 to 3.3). In contrast, women who lost more than 5.0 kg reduced their risk for diabetes mellitus by 50% or more. These results were independent of family history of diabetes. CONCLUSION: The excess risk for diabetes with even modest and typical adult weight gain is substantial. These findings support the importance of maintaining a constant body weight throughout adult life and suggest that the 1990 U.S. Department of Agriculture guidelines that allow a substantial weight gain after 35 years of age are misleading. PMID- 7872582 TI - Occult sleep-disordered breathing in stable congestive heart failure. AB - OBJECTIVE: To determine the prevalence and effect of sleep-disordered breathing in ambulatory patients with stable, optimally treated congestive heart failure. DESIGN: A prospective, longitudinal study. SETTING: Referral sleep laboratory of a Department of Veterans Affairs medical center. PATIENTS: 42 of the 48 eligible patients with stable congestive heart failure and left ventricular systolic dysfunction (left ventricular ejection fraction < or = 45%). MEASUREMENTS: After an adaptation night, polysomnography and Holter monitoring were done in the sleep laboratory. Arterial blood gases and pH were measured, and cardiac radionuclide ventriculography and pulmonary, renal, and thyroid function tests were done. RESULTS: Patients were divided into two groups. Group I (n = 23) had an hourly rate of apnea and hypopnea (apnea-hypopnea index) of 20 episodes per hour or less; group II (n = 19 [45%; CI, 30% to 60%]) had an index of more than 20 episodes per hour. In group II, the index varied from 26.5 to 82.2 episodes per hour (mean +/- SD, 44 +/- 13 episodes per hour; CI, 38 to 51 episodes per hour). Group II had significantly more arousals (24 +/- 12 compared with 3 +/- 3 in group I) that were directly attributable to episodes of apnea and hypopnea, longer periods of time with an arterial oxyhemoglobin saturation of less than 90% (23% +/- 24% of total sleep time compared with 2% +/- 4%), lower arterial oxyhemoglobin saturation during sleep (74% +/- 13% compared with 87% +/- 4%), lower left ventricular ejection fraction (22% +/- 9% compared with 30% +/- 10%), and a significantly increased number of episodes of nocturnal ventricular arrhythmias. Multiple regression analyses showed that left ventricular systolic dysfunction was an independent risk factor for sleep apnea in patients with congestive heart failure. CONCLUSIONS: The prevalence of severe occult sleep disordered breathing is high in ambulatory patients with stable, optimally treated chronic congestive heart failure. The breathing episodes are associated with severe nocturnal arterial blood oxyhemoglobin desaturation and excessive arousals. Severe untreated sleep-disordered breathing may adversely affect left ventricular function, resulting in a vicious cycle that could contribute to death in patients with congestive heart failure. Prospective, longitudinal studies on survival are needed. PMID- 7872583 TI - Upper airway sleep-disordered breathing in women. AB - OBJECTIVE: To investigate the various clinical presentations of sleep-disordered breathing in women. DESIGN: A retrospective case-control study. SETTING: A sleep disorders clinic. PATIENTS: 334 women, aged 18 years and older, seen between 1988 and 1993, who were diagnosed with upper airway sleep-disordered breathing. Controls were 60 women with insomnia and 100 men with sleep-disordered breathing. MEASUREMENTS: Clinical, anatomic, and polygraphic information. RESULTS: The mean lag time (+/- SD) in women between the appearance of symptoms and a positive diagnosis was 9.7 +/- 3.1 years; among participants 30 to 60 years of age, the duration of untreated symptoms differed (P < 0.001) between women and men. Sleep disordered breathing was blamed for divorce or social isolation by 40% of the case patients. Abnormal maxillomandibular features were noted in 45% of the women with disordered breathing. Dysmenorrhea and amenorrhea (which disappeared after treatment with nasal continuous positive airway pressure) were reported in 43% of premenopausal women compared with 13% of persons in the control group of women with insomnia. Thirty-eight women (11.4%) with upper airway sleep-disordered breathing had a respiratory disturbance index of less than 5 and were significantly younger, had a smaller neck circumference, and had a lower body mass index than women with a respiratory disturbance index of 5 or more. CONCLUSION: Physicians should revise their understanding of upper airway sleep disordered breathing so that they notice women with certain craniofacial features, a low body mass index, a small neck circumference, and a respiratory disturbance index of less than 5. These revisions may enable more rapid diagnosis and treatment of women with sleep-disordered breathing. PMID- 7872584 TI - Increased incidence of aortic aneurysm and dissection in giant cell (temporal) arteritis. A population-based study. AB - OBJECTIVE: To determine the frequency of aneurysm and dissection of the aorta in patients with giant cell arteritis and to assess the effects of these events on these patients. DESIGN: Population-based cohort study. SETTING: A multispecialty and a primary care clinic in southern Minnesota. PATIENTS: 96 residents of Olmsted County, Minnesota, who developed giant cell arteritis between 1950 and 1985. The presence of aortic aneurysm, dissection, or both was confirmed using computed tomography, ultrasonography, angiography, or autopsy. RESULTS: 11 of the 96 patients were found to have thoracic aortic aneurysms. In 2 of these patients, the aneurysms were detected when giant cell arteritis was diagnosed. In the remaining 9 patients, the aneurysms occurred a median of 5.8 years after giant cell arteritis was diagnosed. Six of the 11 died suddenly of acute thoracic aortic dissection. Five patients who did not have thoracic aortic aneurysms developed isolated abdominal aortic aneurysms a median of 2.5 years after giant cell arteritis was diagnosed. The incidence of thoracic aortic aneurysm in patients with giant cell arteritis was 999 per 100,000 person-years; the incidence of abdominal aortic aneurysm in these patients was 555 per 100,000 person-years. Compared with all persons of the same age and sex living in Olmsted County, patients with giant cell arteritis were 17.3 times (95% Cl, 7.9 to 33.0) more likely to develop thoracic aortic aneurysm and 2.4 times (Cl, 0.8 to 5.5) more likely to develop isolated abdominal aortic aneurysm. CONCLUSIONS: Giant cell arteritis is associated with a markedly increased risk for the development of aortic aneurysm, which is often a late complication and may cause death. PMID- 7872585 TI - Clinical remission after syngeneic bone marrow transplantation in a patient with AL amyloidosis. PMID- 7872586 TI - Serum levels of free 1,25-dihydroxyvitamin D in vitamin D toxicity. AB - OBJECTIVE: To determine the serum level of free 1,25-dihydroxyvitamin D [1,25 (OH)2D] in patients with vitamin D toxicity and to assess the in vitro effect of differing concentrations of vitamin D metabolites on the free serum levels of 1,25-(OH)2D. DESIGN: 1) A case study of patients hospitalized with vitamin D toxicity after accidentally ingesting a veterinary vitamin D concentrate and 2) an in vitro experiment in which vitamin D metabolites in various concentrations were added to normal serum and their effect was noted on percentage of free 1,25 (OH)2D. PATIENTS: 11 patients (age range, 8 to 69 years) were studied 10 to 40 days after hospitalization for hypercalcemia. MEASUREMENTS: Serum total 25 hydroxyvitamin D (25-OHD) and 1,25-(OH)2D levels were measured by radioreceptor assays. The percentage of free 1,25-(OH)2D was measured by centrifugal ultrafiltration isodialysis and was used to calculate actual free 1,25-(OH)2D levels. In the in vitro studies, vitamin D metabolites [25-OHD; 24,25-(OH)2D; 25,26-(OH)2D; and 25-OHD-26,23 lactone] were added to normal serum in concentrations expected to occur with vitamin D toxicity. The percentage of free 1,25-(OH)2D was measured by isodialysis. RESULTS: All patients presented with marked hypercalcemia (mean calcium level, 3.99 +/- 0.33 mmol/L). Serum 25-OHD levels ranged from 847 to 1652 nmol/L, and total 1,25-(OH)2D levels (mean, 106 +/ 86 pmol/L) were elevated in only three patients. The percentage of free 1,25 (OH)2D (mean, 1.023% +/- 0.366%) was elevated in all nine patients in whom it was measured. Actual free 1,25-(OH)2D levels (mean, 856 +/- 600 fmol/L) were elevated in six of the nine patients. Total 1,25-(OH)2D levels were correlated with 25-OHD levels (r = 0.66; P = 0.03), whereas total and free 1,25-(OH)2D levels were highly correlated (r = 0.957; P < 0.001). In the in vitro studies, the percentage of free 1,25-(OH)2D increased after 25-OHD or 24,25-(OH)2D was added. CONCLUSIONS: Although the patients had normal or near-normal total 1,25-(OH)2D values, most patients had elevated free 1,25-(OH)2D levels. These findings suggest that elevated free 1,25-(OH)2D levels might play a role in the pathogenesis of hypercalcemia in vitamin D toxicity. PMID- 7872587 TI - Health values of the seriously ill. SUPPORT investigators. AB - OBJECTIVE: To assess 1) the health values and health ratings of seriously ill hospitalized patients, their surrogate decision makers, and their physicians; 2) the determinants of health values; and 3) whether health values change over time. DESIGN: Prospective, longitudinal, multicenter study. SETTING: 5 academic medical centers. PARTICIPANTS: 1438 seriously ill patients with at least one of nine diseases who had a projected overall 6-month mortality rate of 50%; their surrogates; and their physicians. MEASUREMENTS: Time-tradeoff utilities (reflecting preferences for a shorter but healthy life) and health ratings. RESULTS: At study day 3, patients had a mean time-tradeoff utility of 0.73 +/- 0.32 (median [25th, 75th percentile], 0.92 [0.63, 1.0]), indicating that they equated living 1 year in their current state of health with living 8.8 months in excellent health. However, scores varied widely; 34.8% of patients were unwilling to exchange any time in their current state of health for a shorter life in excellent health (utility, 1.0), and 9.0% were willing to live 2 weeks or less in excellent health rather than 1 year in their current state of health (utility, 0.04). Health rating scores averaged 57.8 +/- 24.0 (median [25th percentile, 75th percentile], 60 [50, 75]) on a scale of 0 (death) to 100 (perfect health). The patients' mean time-tradeoff score exceeded that of their paired surrogates (n = 1041) by 0.08 (P < 0.0001). Time-tradeoff scores were related to psychosocial well-being; health ratings; desire for resuscitation and extension of life rather than relief of pain and discomfort; degree of willingness to live with constant pain; and perceived prognosis for survival and independent functioning. Scores of surviving patients increased by an average of 0.06 after 2 months (P < 0.0001) and 0.08 after 6 months (P < 0.0001). CONCLUSIONS: Health values of seriously ill patients vary widely, are higher than patients' surrogates believe, are related to few other preference and health status measures, and increase over time. PMID- 7872588 TI - The hepatopulmonary syndrome. AB - OBJECTIVE: To review current knowledge about the hepatopulmonary syndrome, including definition and clinical features, methods for diagnosing it, pathophysiologic mechanisms of the associated vascular dilatations, and considerations in treatment, with emphasis on potential reversibility of the syndrome after liver transplantation. DATA SOURCES: The MEDLINE database from January 1986 to December 1993 and bibliographies of selected articles. STUDY SELECTION: Case studies and series reporting results from patients with the hepatopulmonary syndrome were reviewed. Clinical reviews and animal studies relevant to the hepatopulmonary syndrome were examined. DATA EXTRACTION: Outcomes, including survival and the frequency of reversibility of the hepatopulmonary syndrome, were extracted from available clinical reports. DATA SYNTHESIS: Mild hypoxemia is multifactorial and occurs in approximately one third of all patients with chronic liver disease. The hepatopulmonary syndrome is one cause of hypoxemia that may also cause dyspnea, platypnea, and orthopnea. Intrapulmonary vascular dilatations and the resulting right-to-left intrapulmonary shunt are characteristic of the syndrome. Pharmacologic treatment with almitrine bismesylate, somatostatin analog, and indomethacin and treatment with plasmapheresis have been disappointing. The underlying cause and the predictors of reversibility of the hepatopulmonary syndrome remain unknown, but it has recently been shown that such reversibility is possible and that contrast enhanced echocardiography appears to be the most sensitive diagnostic test for detecting intrapulmonary vascular dilatations. CONCLUSIONS: In the context of persisting uncertainty about the cause and treatment of the hepatopulmonary syndrome, future studies must focus on better understanding the pathophysiology of the hepatopulmonary syndrome, predicting reversibility after liver transplantation, and identifying other treatment options. PMID- 7872589 TI - On politics and health: an epidemic of neurologic disease in Cuba. AB - Political decisions may cause disease. During 1992 and 1993, an epidemic of neuropathy in Cuba--largely overlooked by U.S. physicians--affected more than 50,000 persons and caused optic neuropathy, deafness, myelopathy, and sensory neuropathy. Patients with the neurologic disease responded to B group vitamins, and oral vitamin supplementation of the population curbed the epidemic. Dietary restrictions and excessive carbohydrate intake were the immediated cause of the epidemic; however, the primary cause might have been political. Political changes in eastern Europe had major repercussions on Cuba's economy and food supply. In turn, these changes compounded the effects of internal political decisions in the island, leading toward isolationism and economic dependence on the former Soviet Union. Also, for more than 30 years, the United States has maintained an economic embargo against Cuba. In 1992, the U.S. embargo was tightened by the Torricelli amendment (or the Cuba Democracy Act), which prohibited third-country subsidiaries of U.S. companies from trading with Cuba and prevented food and medicines from reaching the island; this amendment produced a virtual economic blockade. Penuries resulting from all these political events resulted in the largest epidemic of neurologic disease in this century. Physicians may need to use their influence to modify political decisions when these decisions result in adverse health consequences. The American Academy of Neurology has issued a plea to encourage physicians and other health personnel to support efforts leading to lifting of the U.S. embargo against Cuba for humanitarian reasons. PMID- 7872590 TI - Mammographic screening for women aged 40 to 49 years: the primary care practitioner's dilemma. AB - The data from population-based, randomized trials of the mammographic screening of women aged 40 to 49 years are limited by retrospective subgroup analysis, low statistical power, and the use of older mammographic techniques. Nonetheless, meta-analysis involving the most recently reported data from all similarly designed trials shows a 21% mortality reduction in women who have had mammographic screening compared with those in control groups, a statistically significant difference (upper bound of 95% Cl, 0.98). Evidence from modern mammography demonstration projects (which are limited by a lack of control groups and the unavailability of mortality results) also shows that the tumor size, axillary lymph node status, and stage of screening-detected breast cancers in women aged 40 to 49 years indicate that screening is at least as beneficial for these women as it is for those aged 50 to 64 years, for whom mammographic screening is widely accepted. Overall, the evidence suggests that screening will benefit women aged 40 to 49 years, but some argue that the level of proof provided is not rigorous enough to establish the efficacy of screening. In the United States, more than 10,000 deaths per year occur among women who develop breast cancer between the ages of 40 and 49. Thousands of lives are probably lost each year because women are not being screened. We believe that it is much more prudent to endorse mammographic screening now, risking the unlikely subsequent determination that the effort was ineffective, than to withhold screening until it is determined whether "proof" of efficacy will be obtained, risking the loss of so many lives. We urge primary care practitioners to recommend routine mammography for women aged 40 to 49 years. PMID- 7872591 TI - Clinical strategies for breast cancer screening: weighing and using the evidence. AB - When balancing the benefits of screening women for breast cancer against the harms and costs of such screening, one needs to consider the risk for dying of breast cancer, the relative reduction in that risk that will result from screening women in different age groups, and the harms and costs associated with screening. Seven randomized controlled trials provide evidence of the relative risk reduction that results from screening women in different age groups; other studies estimate the harms and costs of screening. These studies indicate that the benefit of screening, expressed as the absolute number of lives extended per 1000 women screened, increases with age and that the harm of screening, expressed as the number of follow-up procedures per cancer detected, decreases with age. Thus, the tradeoff between the benefits and the harms and costs of screening is better for older than for younger women. Because there is no clear cut-point for determining when benefits outweigh harms and costs, it is important to involve women in discussions of breast cancer screening. The women who most need to be involved are those for whom the benefits of screening clearly outweigh the harms and costs and those for whom the benefits and the harms and costs constitute a "close call." For women in both groups, the physician should routinely raise the issue of screening, first eliciting the patient's perceptions and then providing information and discussion about the risk for breast cancer and about the benefits and the harms and costs of screening. Furthermore, the physician should encourage the patient to use her own values to weigh the benefits against the harms and costs, pointing out biases in reasoning and minimizing socioeconomic barriers. Finally, when the benefits obviously outweigh the harms and costs, the physician should make a clear recommendation for screening. PMID- 7872592 TI - Modest weight gain and the development of diabetes: another perspective. PMID- 7872593 TI - Screening mammography in women younger than 50 years of age. PMID- 7872594 TI - Amiodarone and torsade de pointes. PMID- 7872595 TI - Acute hepatitis, interstitial nephritis, and eosinophilia. PMID- 7872596 TI - Hepatitis C virus in saliva. PMID- 7872597 TI - Further ethics resources. PMID- 7872598 TI - Further ethics resources. PMID- 7872599 TI - Langerhans' cell histiocytosis of the head and neck in children. AB - This is a retrospective analysis of a 29-year institutional experience with Langerhans' cell histiocytosis (LCH) in children. Cases of LCH were categorized by disease extent into three groups: group 1, with a solitary focus of LCH; group 2, with multiple non-vital organ foci; and group 3, with vital organ disease. Sixteen patients averaging 7.3 years of age and with 11.0 years of follow-up presented in group 1. One child experienced a spontaneous remission; all other children responded to local treatment. The skull was the most common site of involvement. Eight children averaging 4.6 years in age and with 8.0 years of follow-up presented in group 2; 3 children had diabetes insipidus. Treatment included radical surgery, radiotherapy, and chemotherapy; however, disease persisted in all patients. Iatrogenic complications were a significant cause of morbidity and mortality. Only 1 patient, 1 year of age, presented with lung and liver involvement (group 3). He died after a fulminant course. Current recommendations for diagnosis, evaluation, and treatment of LCH are discussed. PMID- 7872600 TI - Evidence linking the 68 kilodalton antigen identified in progressive sensorineural hearing loss patient sera with heat shock protein 70. AB - Immunoblotting against bovine inner ear extracts has previously identified a 68 kd antigen reactive with 22% to 58% of sera of patients with rapidly progressive sensorineural hearing loss (PSNHL) of suspected autoimmune causation. Efforts to purify and characterize this diagnostic antigen suggest that it is ubiquitous rather than inner ear-specific, and may represent the highly inducible heat shock protein (hsp) 70. The antigens identified by PSNHL sera and anti-hsp 70 monoclonal antibodies copurify on ion exchange and adenosine triphosphate affinity chromatography, and comigrate on one- and two-dimensional gel electrophoresis. Additionally, immunoblotting with positive patient sera shows dramatically increased expression of the 68 kd antigen by bovine kidney cells following heat shock in culture. Reactivity with stress proteins of various classes has been reported in a number of autoimmune diseases; however, anti-hsp 70 appears uniquely associated with ulcerative colitis and PSNHL. PMID- 7872601 TI - In situ analysis of the immune microenvironment of the adenoid in children with and without secretory otitis media. AB - Using monoclonal antibodies and immunohistochemistry, we compared adenoid tissue from 35 children with or without secretory otitis media. Numerous cells infiltrating the reticular crypt epithelium expressed HLA-DR, as did < 10% of the epithelial cells. Of the antigen-presenting cells, CD1a+ dendritic cells showed intraindividual and interindividual variations; CD68+ macrophages and CD22+ B cells were uniformly distributed. The relative frequencies of CD4+ and CD8+ cells were 6.6 +/- 2.0 versus 2.3 +/- 1.2 (p < .001) in the reticular crypt epithelium and 18 +/- 4.5 versus 1.5 +/- 0.9 (p < .001) in the germinal centers. The IL-2 receptor was expressed on < 0.1% of CD3+ T cells. Over 90% of intraepithelial CD3+ T cells were of the CD45RO+ memory phenotype. The proliferation marker Ki67 was almost exclusively found in the germinal centers. That the analyzed parameters showed a similar pattern in both clinical groups suggests that the presence of secretory otitis media may not correlate to specific alterations in the immune microenvironment of the adenoid. PMID- 7872602 TI - Gender-specific vocal dysfunctions in Parkinson's disease: electroglottographic and acoustic analyses. AB - Electroglottographic (EGG) and acoustic recordings were obtained during sustained vowel production in men and women suffering from Parkinson's disease (PD). The computed EGG spectrograms allowed us to differentiate various kinds of phonatory disturbances: intervals with subharmonic energy ("low-frequency segments"), "noise-like regions," and abrupt shifts of fundamental frequency (F0). Female PD subjects presented with a significantly increased portion of subharmonic segments and with significantly more abrupt F0 shifts as compared to both controls and male PD subjects. Presumably, these alterations in spectral energy distribution reflect different oscillatory modes of the glottal source. Thus, PD seems to have a differential impact on phonation in men and women. Conceivably, these gender specific vocal dysfunctions are determined by the well-known sexual dimorphism of laryngeal size. PMID- 7872603 TI - Cytokine regulation of gelatinase production by head and neck squamous cell carcinoma: the role of tumor necrosis factor-alpha. AB - Gelatinases (GLs) belong to a family of enzymes known as matrix metalloproteinases (MMPs), which are produced by both normal and neoplastic cells. These enzymes have been implicated in tumor invasion and metastasis, although the mechanism of regulation of tumor MMP production is unknown. Since our previous studies have shown that numerous cytokines are present in the tumor microenvironment, our goal was to establish the effect of selected cytokines on GL production by both established tumor cell lines and primary cultures of head and neck squamous cell carcinoma (HNSCC). Supernatants of HNSCC cell lines SCC-25 and FADU stimulated with interleukin (IL)-1 alpha and IL-1 beta demonstrated modest induction of 92 kd GL production by zymogram analysis when compared with controls; IL-2, IL-6, and interferon-gamma had no consistent effect on MMP production. Stimulation of cell lines with tumor necrosis factor (TNF)-alpha (10(4) to 10 U/mL), however, dramatically enhanced production of 92 kd GL by both cell lines in a dose-dependent fashion, although tissue inhibitor of metalloproteinase (TIMP) expression was unaffected. Northern blot analysis showed that this enhancement of 92 kd GL occurred at the messenger RNA level. Stimulation of short-term primary tumor cultures with TNF-alpha resulted in significant enhancement of 92 kd GL expression in one of four cultures and enhancement of 72 kd GL expression in all cultures. The observed increase in GL expression by TNF-alpha suggests a role for this cytokine in the regulation of GL expression by tumor cells during invasion and metastasis. PMID- 7872605 TI - Epidermal cell migration and healing of the tympanic membrane: an immunohistochemical study of cell proliferation using bromodeoxyuridine labeling. AB - A monoclonal antibody against bromodeoxyuridine (BrdU) was used to investigate cell proliferation in the tympanic membrane of white rabbits. The BrdU-labeled cells were observed mainly in the epidermis of the annulus, around the malleus handle, and in the anterior and posterior superior quadrants of the normal rabbit tympanic membrane at 2 hours after BrdU injection. At 5 days the localization of the BrdU-labeled cells had changed centrifugally from the malleus handle toward the annulus. This change in the distribution of BrdU-labeled cells suggested that epidermal cell migration is caused by cell proliferation and insertion of newly proliferated epidermal cells at the proliferation center. Immunohistochemical observation of BrdU-labeled cells in the artificially perforated tympanic membrane suggested that the process of healing of the perforation may be as follows. Epidermal cell proliferation in the whole tympanic membrane is accelerated by the perforation stimulus. Then the proliferated epidermal cells migrate to the edge of the perforation. In contrast, proliferation of connective tissue cells and mucosal cells is stimulated only around the perforation, and cooperates with the proliferated epidermal cells to close the perforation. PMID- 7872604 TI - Vascular permeability of the stria vascularis and morphology of the endolymphatic sac in two types of experimental endolymphatic hydrops. AB - We produced two kinds of experimental endolymphatic hydrops. One was induced by obliteration of the endolymphatic sac (ES), and the other was induced by both systemic keyhole limpet hemocyanin immunization and secondary keyhole limpet hemocyanin challenge into the ES. The vascular permeability of the stria vascularis in acute and chronic phases was compared between both models by light and electron microscopy using the tracer method of horseradish peroxidase. Both models showed that the number of strial capillaries showing horseradish peroxidase leakage was significantly higher in the acute phase than in the chronic phase. In the acute phase, the ES showed acute inflammation in both models. In the chronic phase, extensive fibrosis occurred in the ES obliteration model, whereas the ES appeared to have a normal shape in the immunologically induced model. The mechanism of hydrops formation will be compared between the two models. PMID- 7872606 TI - Effect of HA-1A monoclonal IgM antibody on endotoxin-induced proliferation of cultured rat middle ear epithelium. AB - The effect of human monoclonal antibody HA-1A (Centoxin) on the effect of endotoxin on cultured rat middle ear epithelium was investigated. The addition of endotoxin to the standard culture medium revealed a concentration-related proliferative effect on cultured rat middle ear epithelium, leading to cobblestone cells, cell tracks, and stratification of epithelium, whereas rat middle ear epithelium cultured in standard medium grew as a monolayer composed of flat polygonal cells. Addition of HA-1A to standard medium supplemented with endotoxin gave rise to a statistically significant suppression of the proliferative effects of endotoxin on these cells. The morphology of rat middle ear epithelium cultured in the presence of HA-1A and endotoxin showed that these cells still had a tendency to form cobblestone-like cells and cell tracks, but to a substantially lower degree. The present results support the hypothesis that HA 1A suppresses the proliferative and morphological effects of endotoxin on rat middle ear epithelium and may play an important role in the pathogenesis of otitis media. PMID- 7872607 TI - Inhibition of mucociliary clearance of the eustachian tube by leukotrienes C4 and D4. AB - The effect of leukotrienes C4 (LTC4) and D4 (LTD4) and prostaglandin E2 (PGE2) on mucociliary clearance of the eustachian tube was investigated in vitro and in vivo. Normal ciliated epithelium was obtained from the eustachian tube of guinea pigs and incubated separately with LTC4, LTD4, and PGE2 at concentrations of 10( 8) mol/L and 10(-6) mol/L. Ciliary activity was measured photoelectrically. Leukotriene D4 progressively inhibited ciliary activity, while PGE2 promoted it. Leukotriene C4 also induced ciliary inhibition. One milliliter each of 10(-5) mol/L LTC4, LTD4, and PGE2 was directly injected into the tympanic bullae of chinchillas under anesthesia. The middle ears were examined by otomicroscopy, tympanometry, and auditory brain stem response over time. Clearance of middle ear effusion was delayed by LTC4 and LTD4, as compared with PGE2 and the control. These findings indicate that LTC4 and LTD4 inhibit mucociliary clearance of the eustachian tube. PMID- 7872609 TI - Mucocele of the pterygomaxillary space. PMID- 7872608 TI - Atypical myosin heavy chain in rat laryngeal muscle. AB - The myosin content of rat posterior cricoarytenoid and thyroarytenoid muscles was described by means of histochemical, immunohistochemical, and electrophoretic techniques. Laryngeal muscles were dissected and frozen, together with other muscles (extraocular, diaphragm, extensor digitorum longus, and soleus) for comparative purposes, then sectioned serially and stained: 1) histochemically for myofibrillar adenosine triphosphatase reactivity and 2) immunohistochemically for myosin heavy chain (MHC) content with six different antibodies. Other portions of the muscle samples were electrophoresed by a glycerol sodium dodecyl sulfate polyacrylamide gel electrophoresis technique that separates the MHC protein into its specific isoforms. In electrophoretic comparison to limb muscles, the laryngeal muscles contained an additional MHC band we designated as type IIL (type II laryngeal) MHC. On histochemical and immunohistochemical staining, no fibers from the thyroarytenoid muscle and few fibers from the posterior cricoarytenoid muscle could be classified according to the standard fiber type categories established for limb muscles (types I, IIA, IIB, and IIX). These laryngeal muscle fibers appear to represent an atypical fiber type. PMID- 7872610 TI - Penetrating cervical injury caused by a needlefish. PMID- 7872611 TI - Cartilaginous tumors of the larynx. AB - Cartilaginous tumors of the larynx, while rare, will on occasion be encountered by the otolaryngologist in routine daily practice. True laryngeal chondromas are exceedingly rare, and as a consequence, a putative diagnosis of chondroma should be viewed with suspicion. On pathologic examination, laryngeal chondromas usually prove to be small lesions (less than 2 cm in maximum dimension) and may arise in children or adults. Laryngeal chondrosarcomas, by contrast, usually prove to be larger lesions (exceeding 3 cm in greatest dimension) and are typically found in adults. While high-grade chondrosarcomas are readily identifiable on light microscopic study, the distinction between a chondroma and a low-grade chondrosarcoma is often not so clear-cut. Some low-grade chondrosarcomas may show a slight increase in both cellularity and cytologic atypia when compared with chondromas, but the two patterns often overlap. When faced with a limited biopsy specimen of a laryngeal cartilaginous lesion in which neither increased cellularity nor recognizable cytologic atypia is found, a diagnosis of "cartilaginous tumor without obvious evidence of malignancy--further classification dependent on examination of the lesion in its entirety," or words to this effect, is recommended. PMID- 7872612 TI - Idiopathic midline destructive disease. PMID- 7872613 TI - [Experience with the transjugular intrahepatic portocaval shunt]. AB - Liver transplantation and the intrahepatic shunt have changed the management of variceal hemorrhage and refractory ascites. The purpose of this work is to review the results obtained with intrahepatic shunting. From January 1991 to May 1993, 45 patients underwent a transjugular intrahepatic portosystemic shunt. In 23 patients, liver insufficiency was considered moderate and in 21 severe. Indications for the procedure were: variceal bleeding (23), refractory ascites (19) and portal hypertensive gastritis (3). The portocaval gradient was lowered from 24.2 +/- 5.1 mm Hg to 12.9 +/- 3.9 (-47%). The procedure was effective in 78% of variceal bleeders and in 89% of patients with ascites. Thirty-day mortality was 22%. One-year survival was 39%. Liver failure or severe encephalopathy occurred in 27% of patients. Four patients (9%) presented intra abdominal bleeding. Four patients developed renal failure. Transjugular intrahepatic portosystemic shunts are effective in lowering portal pressure and controlling complications of portal hypertension. However, important side effects are present and controlled studies are required to evaluate this new treatment. PMID- 7872614 TI - [Abdominal rectopexy (Orr-Loygue) in rectal prolapse: celioscopic approach or conventional surgery]. AB - One of the treatment modalities for rectal prolapse is abdominal rectopexy, a comparison of the Orr-Loygue procedure, performed by laparotomy and by laparoscopy was done. From June 1981 and May 1993, 31 females and 3 males, with an average of age of 58.8 were operated. Twelve patients were operated by laparoscopy (group I) and 22 patients by laparotomy (group II). Two patients (16.7%) in group I were converted to a laparotomy due in one to operative hemorrhage and in the other to adhesions. Seven patients in group I and 18 in group II had had previous abdominal surgery. Average operative time was 2.56 hours and 2.25 hours for groups I and II respectively. A reduction in post operative hospital stay (5 vs 8.3 days) as well as in intramuscular analgesic requirements (5.5 vs. 14.1 doses) was observed in group I vs. group II respectively. Time to oral intake and cessation of intravenous fluids were also reduced in group I compared to group II (1.0 vs. 3.9 days and 2 vs. 5.8 days respectively). No mortality and minimal morbidity was observed in both groups. No recurrence of prolapse was noted in either group with an average of 12.6 mouths follow-up (2.8 to 17 months). We concluded that rectopexy by laparoscopy is technically feasible and has undeniable advantages over laparotomy. PMID- 7872615 TI - [Factors of recurrence in Crohn disease]. AB - The surgical treatment of complications of Crohn's disease is often postponed, because of the threat of short gut and high recurrence rates. We reviewed retrospectively 286 cases of intestinal resection to evaluate factors influencing the recurrence of Crohn's disease after surgery. Recurrence was defined as the need for reoperation. Risk factors used as independent variables are all subject of controversy in recent literature. These factors included: smoking, blood transfusion, contamination, localisation of the disease, length of resection, microscopic margins and the duration of follow-up. A logistic regression model was calculated, using recurrence as the dependent variable. The mean follow-up is 55 months. Kaplan Meier was used to measure the recurrence rate. Duration of follow-up is the most important variable. The length of resection and the positive margins can statistically predict recurrence (p = 0.046 et p = 0.016), both having a predictive value of 72%. A resection with clear margins decreases the recurrence rate significantly (15%) (p = 0.0025). PMID- 7872616 TI - [Effect of ranitidine on blood alcohol and glucose levels after ingestion of alcohol]. AB - Are alcohol and glucose blood levels modified in fasting subjects taking ranitidine? This experience tries to simulate normal life conditions. Nine men, volunteer, aged from 24 to 29 years old, without any digestive symptoms, ate a standard lunch after five hours of fasting, took 0.35 g of alcohol per kg. Ethanol blood levels, glycemia and blood levels of insulin and glucagon were taken at regular intervals every 10 to 15 minutes during all the experiment (120 minutes). After the initial experiment, all subjects took 150 mg of ranitidine p.o. b.i.d. during seven days. Afterward they were submitted to the same protocol. Between both experiments no differences were found on blood levels of ethanol. Peak concentration, decreasing rate, and biodisponibility (estimated by area under the curve) did not change. There was a tendency to have a faster decrease in glucose blood level (p < 0.05). This study does not show any significant modification of ethanol metabolism after taking ranitidine p.o.; those results are differing from data already found with studies using cimetidine. PMID- 7872617 TI - [Cystic tumors of the pancreas: apropos of 36 cases]. AB - Cystadenomas and cystadenocarcinomas are rare cystic tumors of pancreas. Clinicopathological features and treatment of these neoplasms have been studied in 36 patients over a 10-year period (1983-1993). There were 19 cystadenomas (CA) either serous (n = 13) or mucinous (n = 6) and 17 cystadenocarcinomas (CAC). Eighteen CA (95%) were found in women. CAC were found equally between both sexes. Median age was 63 years and was the same for CA and CAC. Ultrasound gave correct diagnosis of CA or CAC in 64% and CT-scan in 77%. The majority of CAC (n = 15) were localized in the head of the pancreas. CA had no preferential localization. 24 patients (66%) underwent including resection (n = 20) and biopsy (n = 4). Four other patients had a percutaneous biopsy and 8 were observed. Hospital mortality was 8%. Complications included gastric atony (n = 4) and pancreatic fistula (n = 2). Four-year actuarial survival is 63% for resected CAC and 100% for resected CA. In conclusion, most cystic pancreatic tumors are found in women. Malignant lesions are found predominately in the head of the pancreas. Modern imaging technics combined with clinical presentation are reliable in obtaining a diagnosis. Resection remains the treatment of choice. PMID- 7872618 TI - [Results of anal sphincteroplasty for post-traumatic incontinence: with or without colostomy]. AB - Surgical repair of the anal sphincters after previous trauma is generally successful. In earlier publications, a protective colostomy was recommended but in most recent series colostomy is omitted. We have been through both phases and this is the first comparative study done on 82 consecutive repairs: 45 with colostomy from 1977 to 1986 (Group I) and 37 without colostomy from 1986 to 1992 (Group II). Causes of trauma were obstetrical: 50, surgical: 24 and violence: 5. Apart from colostomy related morbidity, postoperative complication rates were similar in the two groups. Results were graded excellent, good, fair or poor according to continence to solids, to liquids and soiling. Good and excellent results were obtained in 82% (Group I) and 87% (Group II) after a mean follow-up duration of 42 and 23 months respectively. Furthermore there was no difference between Group I and II in the rate of good/excellent results for cases who had undergone prior repairs (98% v. 100%) and also when the duration of incontinence was more than 10 years (71% v. 83%). We conclude that colostomy is not a determinant factor in the outcome and is therefore not required, avoiding all colostomy related morbidity and disability. PMID- 7872619 TI - [Variations of body composition by bioelectric impedancemetry after major surgery]. AB - Body water variations are traditionally measured postoperatively by fluid balance and body weight. Bioelectrical impedance assessment permits the evaluation of body composition, i.e., lean body mass, body fat and total body water. We compared the traditional method (body weight and fluid balance) with bioelectrical impedance assessment while estimating body water. Body weight, fluid balance, resistance, reactance, lean body mass, body fat, total body water, triceps skinfold and total protein blood level were measured prospectively (preop, and on days 1, 3 and 5 postop) in 30 patients admitted for major surgery (thoracic, abdominal or vascular). The results suggest that body composition changed significantly with time (p < .05); in all 3 surgical groups. There was a low correlation between total body water measured by bioelectrical Impedance and fluid balance. Bioelectrical impedance assessment is sensitive to body water changes but appears to overestimate these variations compared to the traditional method. PMID- 7872620 TI - [Efficacy and safety of prophylactic preoperative administration of low-dose warfarin in cemented total knee prostheses]. AB - One hundred and fifty six consecutive cemented total knee arthroplasties (TKA) in 147 patients (39 males, 108 females, mean age: 67) received preoperatively low dose-warfarin for thromboembolic prophylaxis. Warfarin 10 mg was given the night before surgery and warfarin 5 mg the night of surgery. Thereafter, the dosage was adjusted to maintain a prothrombin time between 1.2-1.5 times control (INR = 2.0 3.0). The screening for any deep vein thrombosis (DVT) in the operated limb was by ascending venography. The reported incidence of DVT after TKA without prophylaxis is superior to 50%, more than 10% of those are proximal DVT. In this study, the overall incidence of DVT is down to 22.4%. Only five patients (3.4%) had a proximal DVT. There were no deaths and no clinical pulmonary embolisms. Patients with venous insufficiency had a significantly higher incidence of DVT (36.7%, p = 0.05). The average blood loss was 406 ml. Three major local bleedings occurred (2.0%). At one year follow-up, there were no infections. Low dose warfarin is efficacious in reducing DVT formation with TKA. It is safe and does not create excessive bleeding in cemented TKA. PMID- 7872621 TI - [Intraoperative three-dimensional evaluation of Cotrel-Dubousset's procedure for the treatment of idiopathic scoliosis]. AB - In order to evaluate with accuracy the tridimensional (3D) vertebral correction induced by the surgical correction of idiopathic scoliosis with Cotrel-Dubousset instrumentation and technique, we have developed a new per operative measurement system based on 3D digitization with magnetic fields. This method has been used on 23 adolescent patients treated with surgical correction. A statistically significant change in vertebral 3D orientation of 11.4 degrees +/- 5.6 degrees has been found. The measurement repeatability was +/- 2.5 degrees. We conclude that the Cotrel-Dubousset technique truly realizes a 3D correction of the thoracic and lumbar spine of adolescent idiopathic scoliosis. PMID- 7872622 TI - [Assays of cytotoxicity of the Nickel-Titanium shape memory alloy]. AB - The equiatomic Nickel-Titanium (NiTi) alloy has exceptional mechanical properties such as shape memory and superelasticity. It already has applications in orthodontics and is a promising orthopaedic biomaterial. Cytocompatibility studies must therefore be undertaken. The objective of this study is to determine the biological response that NiTi elicits compared to other orthopaedic metals currently used in orthopaedic surgery. Cytotoxicity tests constitute an efficient first step in a biocompatibility study and contribute to reduce animal use in laboratory. Direct contact and agar diffusion cytotoxicity assays were performed following ASTM standards #F813-83 and #F895-84 respectively. Confluent L-929 fibroblasts culture plates were incubated (directly or under an agar bed) in presence of NiTi, titanium (Ti), vitallium (Co-Cr-Mo) and 316L stainless steel discs. Following exposition to specimens, a vital dye was added to the plates. All cultures were evaluated for cytotoxic reactions, under light microscopy. Direct contact and agar diffusion assays indicated that all metals tested induced a mild biological reaction. Specimens were ranked according to an index of biological response, they are enumerated here in decreasing order of cytotoxicity: NiTi approximately Co-Cr-Mo >> pure grade 4 Ti approximately pure grade 1 Ti approximately Ti 6A1 4V approximately 316L stainless steel. Furthermore, plasma surface modification increased the cytocompatibility of NiTi. PMID- 7872623 TI - [Value of Head-Shaking's test in the pre- and the postoperative vestibular assessment]. AB - The value of Head-Shaking maneuver has brought scientific controversies regarding its role as a clinical tool. In the following publication, we explain the discrepancies between the different studies and find out the role of such a maneuver for clinical evaluation during the pre and post operative period. We showed the influence of the diagnosis and the importance of time interval in the post Head-Shaking responses. PMID- 7872624 TI - [Urinary excretion of acetylated polyamines after heart transplantation in dogs]. AB - Increase in urinary polyamine levels after transplantation was suggested to be an indicator of organ rejection but immunosuppression therapy could also give rise to these polyamines. To test this hypothesis, the urinary excretion of N acetylputrescine (Nap) and N-acetylspermidine (Nas) was studied in 36 dogs. Two groups (n = 6) underwent cervical heterotopic heart transplantation. Three other groups (n = 6) were given different immunosuppression treatments without having any surgery and one group (n = 6) had a sham cervical operation. Urine samples and percutaneous transmural biopsy of the transplanted heart were collected daily. The acetylated polyamines were measured with high performance liquid chromatography (HPLC). Immunosuppression of the transplanted dogs with cyclosporine, imuran and prednisone during the postoperative period caused a significant increase (p < 0.05) in the excretion of Nas averaging 512 +/- 122, 929 +/- 337, 507 +/- 207, 1008 +/- 665, 674 +/- 273 nmol/mg of creatinine respectively compared to 197 +/- 31, 149 +/- 30, 203 +/- 56, 177 +/- 40, 226 +/- 62 nmol/mg of creatinine. The excreted levels of Nap for the same group were 594 +/- 202, 707 +/- 138, 1007 +/- 270, 1055 +/- 358, 827 +/- 270 nmol/mg of creatinine compared to 71 +/- 24, 169 +/- 36, 150 +/- 23, 136 +/- 29, 197 +/- 32 nmol/mg of creatinine (p < 0.05) in the control group of sham operated animals. A significant excretion of Nas and Nap was also observed between the transplanted dogs under immunosuppression and the immunosuppressed but non-operated animals, as well as with the non-operated animals that were given cyclosporine only.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872625 TI - [Pulmonary autograft as aortic valve replacement in children]. AB - The aortic stenosis represents 5% of all congenital cardiac pathology. The conventional treatments often do not give very satisfactory results. Since 1990, as alternative to the traditional aortic valve replacement, we used, in our institution, the Ross procedure (pulmonary autograft). This consists in using the pulmonary valve as an autograft in aortic position to replace the diseased valve. Then, the pulmonary outflow is reconstructed with a cryopreserved homograft. This study includes 15 patients, aged between 16 months and 18 years, treated with this technique since 1990. There has been no mortality. All the patients are alive at the follow-up, and all in NYHA functional class I. No reoperation has been necessary for valvular dysfunction. The post-operative doppler study at aortic level demonstrated those gradients: Mean + SD, 3.8 +/- 8.1 (range 0-23). No regurgitation haemodynamically important has been recorded at aortic level nor in the pulmonary position. Post-operative gradients at pulmonary level were: Mean + SD, 14.6 + 10.6 (range 14-32). PMID- 7872626 TI - [Predictive factors of survival after mitral valvuloplasty]. AB - Survival and freedom from reoperation following mitral valvuloplasty (MV) was evaluated in 54 patients (pts) between October 1973 and December 1992. Ages of 35 men and 19 women averaged 49 years (+/- sd:18 yrs). Preoperative NYHA class was II or III in 48 patients (89%) and class IV in 6 pts. At surgery, degenerative disease was present in 43 patients (80%), rheumatic in 8 pts (14%) and congenital in 3 pts (6%). Annuloplasty (Carpentier 18, Duran 27, others 3) was performed in 48 pts and was the sole procedure in 6 pts. Six pts underwent valvuloplasty without annuloplasty. Associated procedures were performed in 18 patients (33.3%). Operative mortality was 6% (3 pts). Follow-up ranged from 1 to 164 months with a mean of 39 mo. (+/- 5 mo.). Survival at 5 years was 89 +/- 8% and freedom from reoperation was 85 +/- 9%. NYHA status was significantly improved following mitral valvuloplasty (p < 0.00001). Operative complications and unfavorable post-operative NYHA status were significantly predictive of death (p < 0.05). Prior cardiac surgery at the time of MV and post-operative unfavorable NYHA status were associated with increased incidence of reintervention (p < 0.05). We conclude that improved post-operative NYHA status heralds excellent long term survival and increased freedom from reoperation following mitral valve repair. PMID- 7872627 TI - [Aortic valve replacement in children]. AB - From January 1970 to January 1993, 47 aortic valve replacements have been performed in children aged 166.8 +/- 50 months. The valvular pathology was congenital in 39 patients and associated cardiac anomalies were present in 31 cases. 30 children had a previous surgical procedure on the aortic outflow. Seven bioprosthesis and 40 mechanical valves have been implanted. At the time of surgery, an additional major cardiac correction has been performed on 17 occasions (Konno, Bentall, Fontan, correction of truncus arteriosus etc.). While no death occurred in the group subjected only to aortic valve replacement, 7 of the 17 patients where a major cardiac procedure was added died. During a mean follow-up of 61.2 +/- 59.1 months, 3 late deaths occurred, 2 of them non related to valvular surgery. Three reoperations have been performed, in two instances for replacing a degenerated bioprosthesis. One thromboembolic event occurred as well as one temporary episode of haemolytic anaemia. No haemorrhagic complication has been observed. While the results of isolated aortic valve replacement in children are excellent, the risk for hospital death is increased substantially when a major cardiovascular procedure is added to valve replacement, and because of rapid deterioration, the heterografts are now contra-indicated in children. PMID- 7872628 TI - [Epidural stimulation in the treatment of refractory angina]. AB - Twelve patients with refractory angina pectoris previously treated with angioplasty or coronary bypass and under optimal medical therapy were treated with spinal cord electrical stimulation (SCES) at the C7 to D2 level since 1988. Six patients had a significant improvement of symptoms confirmed by a reduced incidence of chest pain and decreased used of nitroglycerin. Three patients required removal of electrode (heart transplantation, inadequate comprehension and foreign body reaction). These patients did however benefit from the effect of SCES for sometimes. Three patients died. The SCES may improve the quality of life by reducing the incidence of chest pain in patients previously uncontrolled with maximal medical and surgical therapy. PMID- 7872629 TI - [Thoracic "staging" by videothoracoscopy: a new technique]. AB - We are describing a technique of pre resectional staging of thoracic neoplasm by video assisted thoracic surgical (VATS) techniques. This method was applied on 27 patients, when the lymph nodes II, III, IV, VII, VIII and IX were biopsied or excised. In two cases (2) we were forced to proceed to open thoracotomy for staging because of extensive adhesion. In the other 25 patients, the surgical staging was the same as the VATS staging in 92% of the cases. This technic has obvious advantages for lower mediastinal nodes (100%). VATS should be considered among other staging procedure for thoracic neoplasms. PMID- 7872631 TI - [Development of the frontal sinus after frontocranial remodeling for craniostenosis in infancy]. AB - General considerations about frontal sinus development are discussed. This retrospective radiological study concerns 90 craniosynostoses among 850 cases operated in the Cranio-Facial Unit (1976-88, Hopital Necker des Enfants Malades, Paris, France). The incidence of frontal sinus development is compared between a control group and the craniosynostoses group with a mean age at surgery of 3 years and a mean follow-up of 6.5 years. Pneumatization of the frontal bone seemed to vary according to the type of surgery and the age at review, but was not linked to sex and age at surgery. A classification of fronto-cranial remodelling is suggested. PMID- 7872630 TI - [Radiological changes of talc pleurodesis in cases of effusion]. AB - This study is based on the observations of 86 pleurodesis done by talc insufflation during thoracoscopy in 82 patients suffering from benign (8%) and malignant (92%) pleural effusions. Serial chest films were obtained on every patient. Chest computed tomography was obtained in ten patients. The most frequent finding seen in the early phase and one month later was the appearance of loculations (94%) in selective areas of the thorax. Occasionally they take the appearance of airfluid levels (22%). These loculations are characteristically located in the axillary (60%), intrafissural (30%) and paramediastinal (34%) areas of the chest. In the late phase with a mean evolution time of 6 months, these loculations evolve in 77% of patients in areas of pleural thickening. CT of the chest demonstrates the presence of characteristic pleural thickening in the form of coarse (5/12) and/or fine linear densities (7/12) corresponding to talc deposits, on the pleural surface. These modifications are shown by light microscopy examination of the pleural done at the autopsy. PMID- 7872632 TI - [Glabellar morphology after frontocranial remodeling for craniosynostosis in infancy]. AB - This retrospective clinical and radiographic study concerns 75 cases of craniosynostoses among 850 cases operated in the Craniofacial Unit of Necker's Hospital for Sick Children (1976-1988, Paris, France). The correlation between frontal sinus development and glabellar morphology was analyzed. When there was a significant advancement of the supraorbital ridge the projection of the glabella was satisfactory without any frontal sinus. When no significant advancement was performed, the pneumatization of the frontal bone was as frequent as in the general population and was dependent upon the underlying frontal sinus. PMID- 7872633 TI - [Scalp reconstruction after avulsion: emergency microsurgery and secondary tissue expansion. Apropos of 3 cases caused by farming machines]. AB - Total scalp avulsion is an uncommon accident. Three recent cases illustrate our surgical procedure. Small and central hair-bearing avulsed scalps can be treated by secondary scalp expansion (1 case). Large hair-bearing scalp (> 400 cm2) or including aesthetic relief should be treated by microsurgical reimplantation. Venous grafts allow vascular anastomoses beyond the intimal trauma area. Secondary expansion of reimplanted tissue (2 cases) eliminates scalp defects after initial necrosis. Thus, in the cases of total scalp avulsion even with high risk of failure (long time elapsed since injury, significant crush, part being in bad condition, two levels avulsion...), reimplantation has to be performed according to localization and size of avulsion. A secondary procedure with using expansion of the remaining replanted scalp is possible. PMID- 7872634 TI - [Metatypical carcinoma. Apropos of 4 cases]. AB - The authors describe the anatomopathological, clinical and evolutive characteristics of the metatypical carcinoma, based on four cases and on the existing literature. Evolution of these tumors, with a maxillo-facial preferential location, is usually longer than for other cutaneous carcinomas. Cases presented in this article illustrate the severity of such lesions, whose treatment requires extensive amputations and rather unusual reconstruction procedures. PMID- 7872636 TI - [Use of myoplasty after acute mediastinitis occurring after heart surgery. Apropos of 167 cases]. AB - Infected median sternotomy often requires open wound management. A large thoracic defect usually results in subsequent exposure of heart, great vessels, aorto coronary bypass grafting or vascular prosthesis. After thorough wound debridement, coverage with muscle transposition was carried out in a series of 167 cases observed over a period of 10 years. Transposition of both pectoralis major muscles on internal pedicles was performed in 75 cases. In 27 of these cases, internal mammary grafting did not preclude their use. Since 1986, intrathoracic transposition of the trapezius muscle has been our treatment of choice in 25 cases, most frequently combined with a double pectoralis major transposition. Rectus abdomini muscle flap was seldom used alone whereas latissimus dorsi was mainly used as a salvage flap. Muscle transposition provided effective heart and great vessel protection after acute hemorrhage in 18 cases. This series confirms that mortality and mean hospital stay have decreased dramatically since the routine use of muscle transposition. PMID- 7872635 TI - [Treatment of Darier-Ferrand tumors of the head and neck. Retrospective analysis of 20 cases]. AB - Dermatofibrosarcoma protuberans is an unusual cutaneous neoplasm. Because of its high propensity for local recurrence, a wide and deep excision is recommended as the only satisfactory treatment. This tumour can raise difficult problems of reconstruction to plastic surgeons particularly when located in the face. The authors present a retrospective study of twenty cases of dermatofibrosarcoma protuberans of the head and neck treated at the Saint-Louis hospital over a period of twelve years. PMID- 7872637 TI - [Pectoralis major muscular flap in thoracic substance loss following mediastinitis. Apropos of 7 cases]. AB - Mediastinitis is a rare complication but can occur after any form of cardiac surgery via midline sternotomy. Despite early diagnosis, management in intensive care and appropriate treatment, the prognosis remains severe. Progression towards a chest wall defect, exposing a sternal flap is not uncommon and requires reconstructive surgery because of the potential life-threatening risk. Among the techniques currently used, the authors emphasize the value of pectoralis major myoplasty centered on perforating vessels derived from the internal mammary artery according to the technique described by Nahai in 1982. They have performed this procedure in 7 patients with a high-risk context, always using a single muscle, and also assessed its technical simplicity, low morbidity, absence of obvious functional handicap associated with the aesthetic aspects by means of regular review with a mean follow-up of 18 months. PMID- 7872638 TI - [Full thickness reconstruction of the anterior chest wall with osteomusculocutaneous flap of the latissimus dorsi muscle]. AB - Full thickness chest wall reconstruction must restore a leak-free and semirigid chest wall that allows good respiratory function. We present five consecutive cases of chest wall reconstruction with skeletal frame reconstruction by an osteomusculocutaneous latissimus dorsi flap. This flap allows transfer of the 11th and 12th ribs. The chest wall resection was performed for chest wall sarcomas (four cases) and radionecrosis (one case). The functional results are good. The bone scan showed the good vitality of the transferred ribs. This flap has the advantages of an autologous vascularized bone transfer. It is a useful flap for large full thickness chest wall reconstructions that need a skeletal frame reconstruction. PMID- 7872639 TI - [Breast reconstruction in Poland syndrome. Apropos of 9 cases]. AB - The authors describe their experience of breast reconstruction in Poland's syndrome and analyse 9 cases (eight females, one male) between 1981-1991. The mean age was 25 years (17-53 years). Three women were operated by the Mouly Dufourmentel surgical procedure: translation of the homolateral latissimus dorsi muscle flap with a mammary prosthesis. The muscle flap was used alone in the male. Mammary prostheses were performed alone in four other women. Breast asymmetry was corrected by mammaplasty alone in one woman. In three cases, in order to achieve optimal symmetry, the controlateral ptosed hypertrophic breast was corrected (two cases in the same procedure, one case later). In three cases, a nipple-areolar restoration was performed at the patient's request. These results are analysed with an average follow-up of 5.4 years (2-11 years) and are compared to the literature data. PMID- 7872640 TI - [Tissue expansion in mammary reconstruction and asymmetry. Apropos of 24 prostheses]. AB - Based on a 24 mammary expansion implants performed in 14 cases of deferred breast reconstruction and in 7 cases of asymmetry, the authors analyze their results and indications according to data reported in the recent literature data. In breast reconstruction, expansion represents a relatively simple surgical procedure allowing an increase of local tissues without any additional scars. Its indications correspond to the gap left between simple prosthesis and musculo cutaneous flaps and are based on a clinical analysis of the volume and quality of mammary tissues considering that radiotherapy constitutes more factor of morbidity than a real contra-indication. A strict selection of patients allows reduction of the complications (6% prosthesis extrusions and 6% contractures in this series) that remains quite high (30%) in the literature. Based on two main operative steps, the reconstruction needs, in the great majority of cases, several complementaries operative sequences increasing to 2.4 in their series, and to 2.6-2.8 the average number of operative steps in literature. For breast asymmetry, expansion was correlated in this series to a higher incidence of complications and especially capsular contractures, leading to a limitation of their indications to cases in which the benefit is maximal in relation to an important glandulocutaneous deficit. These indications are in which hypoplasia with superointernal malposition of the nipple areola complex where the effect of expansion is maximal in the inferointernal mammary area and tubular and tuberous breasts, in which expansion allows a widening of the base of the breast and breaks the fibrous ring at the base of the breast. PMID- 7872641 TI - [Surgical treatment of hidradenitis and Fox-Fordyce disease of the nipples]. AB - Hidradenitis suppurativa and Fox-Fordyce disease are apocrine sweat gland diseases, characterized by chronic and recurrent forms, with frequently unsatisfactory management and physical discomfort. The localisation to the breast areola is well known but infrequent. A new surgical treatment of areolar involvement is presented. This technique includes: dermal detachment of the areola safeguarding the nipple, excision of the underlying apocrine sweat glands, areola fixation like a flap-total skin graft. This very simple procedure allows definitive treatment without aesthetic impairment. Two cases of areolar involvement are presented. PMID- 7872642 TI - [Ketanserin and random skin flaps. An experimental study in the rat]. AB - This prospective randomised study in a rodent model was designed to analyse the value of a serotonin antagonist, ketanserin, on the survival of random skin flaps in Wistar rats. Our study demonstrates the statistical value of this molecule. The surface of skin necrosis was statistically lower in the group of rats treated with pre and post operative subcutaneous injection of ketanserin. PMID- 7872643 TI - [Increased viability of skin flaps using naftidrofuryl. An experimental study in the Wistar rat]. AB - The effect of a vasodilator (naftidrofuryl) was evaluated in an experimental study in rats concerning the viability of a skin flap. The reference flap is a dorsal skin flap deliberately shaped very long in order to obtain necrosis of its distal extremity. This necrosis is measurable and sufficiently reproducible. Using a comparative study between a control group of ten rats and a group of rats treated by intraperitoneal injections of naftidrofuryl for ten days, the authors demonstrated a significant difference between necrosis in the two groups. Naftidrofuryl treatment increases the length of the viable part of the skin flap in rats. This product achieves a kind of medicinal autonomy much easier than a surgical autonomy. PMID- 7872644 TI - [Liposuction and extensive cutaneous necrosis. Apropos of a clinical case]. AB - The massive use of hypertonic solution in subcutaneous tissue inevitably causes a necrotic reaction whose severity is directly correlated to the extent of infiltration, involving, as in the present case, all of the abdomen and the anteromedial surface of the thighs. This infiltration was performed for ultrasound treatment as part of liposuction in which the cutaneous swelling must be particularly marked in order to obtain full benefit from this technique. The direct action of ultrasound itself cannot be incriminated in this case. The present case developed was abdominocrural necrosis requiring six weeks of hospitalisation, including twelve days in the intensive care unit and skin cover by split skin grafts after debridement. Although this complication is not specific to liposuction, the quantities of saline regularly infiltrated with this technique carry a high risk of this complication, for which the doctor is inevitable responsible, even if it is due to a confusion on the part of paramedical staff. PMID- 7872645 TI - [XXIII Colloqium of the Society of Experimental Neuroendocrinology. Sophia Antipolis, 1-3 September 1994. Abstracts]. PMID- 7872646 TI - [12th French Congress of Endocrinology. Toulouse, 8-10 September 1994. Abstracts]. PMID- 7872647 TI - Report and abstracts of the Third International Workshop on Chromosome 9. Cambridge, United Kingdom, 9-11 April, 1994. PMID- 7872648 TI - The genetic affinity of Polynesians: evidence from Y chromosome polymorphisms. AB - Y-linked polymorphisms were studied in a sample of 60 Polynesians, and results were compared with findings from studies on other major population groups. Three previously unreported 49a/TaqI haplotypes were observed, two of which possess a new polymorphic fragment named I2. Frequency data for the 49a/TaqI, XY275, pDP31 and Y Alu polymorphisms indicate that Polynesians have greater affinity to Caucasoids than to African populations. Similar population frequency trends were not observed for the p21A1/TaqI polymorphism, supporting the hypothesis that this polymorphism has arisen more than once. PMID- 7872649 TI - Evidence of mitochondrial DNA diversity in South American aboriginals. AB - The absence in South American aboriginals of an Asian-specific marker, a 9-bp deletion between the genes for the second subunit of cytochrome oxidase II and lysine transfer RNA in region V, has been interpreted as a bottlenecking effect at the Isthmus of Panama during the peopling of the Americas. We screened mitochondrial DNA (mtDNA) for this 9-bp tandem repeat and for polymorphisms in specific regions of the mtDNA in 2 ancient and 31 contemporary samples from South American aboriginals. We found additional (mtDNA) diversity in South American aboriginals in three ways. First, an Asian-specific marker not previously reported in South American aboriginals was identified by a sequencing analysis in both the contemporary Andean and Amazonian aboriginal peoples. Second, two new haplotypes so far unique to South American aboriginals were found. Additionally, we show that South American aboriginals fall into discrete populations. These results suggest that the prehistoric colonization of South America is the outcome of multiple migrations; the data do not support a bottlenecking effect at the Isthmus of Panama. PMID- 7872650 TI - Genetic epidemiology of hereditary non-polyposis colorectal cancer syndromes in Modena, Italy: results of a complex segregation analysis. AB - Complex segregation analysis was conducted in a series of patients with hereditary non-polyposis colorectal cancer (HNPCC) ascertained through probands registered in the Cancer Registry of the Health Care District of Modena in Northern Italy. Altogether there were 71 nuclear families segregating for HNPCC in 28 pedigrees. The analysis favoured the two-loci model, in which the segregation at the major locus is compatible with codominant transmission with a frequency of 0.0044 for the high-risk allele for HNPCC and a lifetime penetrance of 0.728 for heterozygotes. PMID- 7872651 TI - Oxidized low-density lipoproteins delay endothelial wound healing: lack of effect of vitamin E. AB - The purpose of this study was to examine the influence of oxidized low-density lipoprotein (oxLDL) on endothelial regrowth in an in vitro wounding model and the possible protection afforded by vitamin E (E). Endothelial cells grown on micropore filters were wounded by scraping and allowed to reestablish growth on denuded areas in the presence of LDL or oxLDL (25-200 micrograms/ml), linoleic acid (FA, 90 microM) or linoleic acid hydroperoxide (OFA, 15 microM) for 24 h. Some monolayers were pretreated with 25 microM E for 24 h. Transendothelial albumin movement was used as a measure of endothelial barrier function and as an indicator of endothelial monolayer regrowth. Exposure to levels of oxLDL as low as 25 micrograms/ml for 24 h resulted in depressed endothelial monolayer regrowth, whereas native LDL was without effect and pre-enrichment with 25 microM E offered no protection. In comparison, E pre-enrichment improved endothelial regrowth to control levels in FA- and OFA-treated cultures, unlike oxLDL-treated cultures. It is concluded that circulating oxLDL may reduce regrowth of wounded endothelium and supplemental E may not offer protection. Moreover, fatty acids or their hydroperoxides are unlikely to be involved in this effect. PMID- 7872652 TI - [Nutritional use of lentil proteins in the young rat]. AB - The nutritional utilization of the lentil was compared to that of casein, used as the only protein food in young rats at two different ages: weanling and 10 days thereafter. Cooking allowed a better intake and digestive utilization of lentil crude protein by the weanling rats. In this case, methionine showed to be the first limiting factor. When lentil diets were given to the older rats, their intake and growth rates reached the level of the control rats. In this case, the free amino acid pools in the muscles were found increased in the group on cooked lentils as compared to that on raw lentils or the control group. PMID- 7872653 TI - Enzymes of the gamma-glutamyl cycle are programmed in utero by maternal nutrition. AB - Exposing the rat fetus to maternal low-protein diets during gestation has been shown to programme a number of metabolic and physiological changes. The present study examines the effects of maternal dietary manipulation upon glutathione cycle enzymes in the rat. Pregnant rats were fed either a non-purified chow diet or purified diets containing 18, 9 or 6% casein. Enzyme activities in the resulting offspring were determined at 4 weeks of age. Weanling pups exposed to the chow diet in utero had significantly lower activities of the glutathione synthetic enzyme gamma-glutamylcysteine synthetase in liver and lung than rats exposed to purified diets. Glutathione peroxidase activity in the liver also tended to be lower in these animals. Glutathione reductase activity in liver was negatively correlated with maternal protein intake, with rats exposed to 6% casein in utero having a significantly raised activity of this recycling enzyme, relative to controls exposed to 18% casein. These data are consistent with the hypothesis that components of maternal diet, including the level of protein intake, programme glutathione cycle enzymes, or production of their regulatory elements, in utero. PMID- 7872654 TI - Do trans fatty acids impair linoleic acid metabolism in children? AB - Trans isomeric fatty acids disturb the metabolism of essential polyunsaturated fatty acids in animals and in premature infants. We assessed whether similar effects may also occur in healthy children. Plasma phospholipid fatty acid composition was analysed in 53 apparently healthy children aged 1-15 years (mean 7.5 years). Trans fatty acids were found in all samples and contributed 1.78 +/- 0.10% (w/w, mean +/- SEM). There was no relation of the major trans isomer octadecenoic acid and of total trans fatty acids to the precursor essential fatty acid linoleic acid. In contrast, we found significant inverse correlations of trans octadecenoic acid and total trans isomers to the principal n-6 metabolite arachidonic acid as well as to the sum of all n-6 metabolites. Furthermore, there was an inverse correlation of total trans fatty acids to the ratio of arachidonic to linoleic acid, an indirect indicator of linoleic acid conversion. These findings are compatible with inhibition of arachidonic acid biosynthesis by trans fatty acids. Since the availability of long-chain polyunsaturated fatty acids, including arachidonic acid, is of essential importance for tissue growth and development, these findings question the safety of high dietary trans fatty acid intakes in childhood. PMID- 7872655 TI - Early biochemical events in mice exposed to cycas and fed a Nigerian-like diet. AB - Changes in colonic faecal microflora, enzymes of colonic energy metabolism, of cell proliferation and lipid profile in the serum and colon were studied in 48 mice exposed to cycas and fed a Nigeria-type diet. The animals were divided into three diet classes of 16 mice per class, and each class of animals was fed ad libitum either a normal diet, a high-carbohydrate high-fibre (HCF) diet or a high protein high-fat (HPF) diet. Each diet class was subdivided into two equal groups of 8 animals each. One group was fed a diet type (acted as the diet control) without cycas, and the other group was fed the corresponding diet with cycas. The study period lasted for 3 weeks. The colonic faecal materials were acidified in the HCF-fed mice compared with the other diet-fed mice. Faecal beta-glucuronidase activity was significantly (p < 0.05) increased in the cycas-fed mice compared with the diet controls. Feeding mice with the HPF diet significantly (p < 0.05) increased beta-glucuronidase and mucinase activities. Colonic phosphofructokinase, glucose 6-phosphate dehydrogenase, lactate dehydrogenase and hyaluronidase activities were also significantly (p < 0.05) elevated in the cycas treated mice. Feeding mice with the HPF diet also significantly (p < 0.05) increased these enzyme activities. Mice fed with the HCF diet significantly (p < 0.05) lowered serum total cholesterol, triglyceride and colonic total lipid. Colonic phosphatidylethanolamine and phosphatidylcholine were significantly (p < 0.05) increased in the HPF-fed mice. This study shows that the HCF diet alters the colonic faecal environment, colonic energy metabolism and hyaluronidase activity in ways which suggest its protective ability against the development of colon cancer in mice. PMID- 7872656 TI - Influence of dietary supplementation with fish on plasma fatty acid composition in coronary heart disease patients. AB - The effects of dietary supplementation with fish on plasma fatty acid levels were studied in 20 coronary heart disease patients who had suffered acute myocardial infarction. The study was divided into three periods: hospital admission, after 8 weeks on a heart-healthy diet designed for patients with ischemic heart disease, and after 4 weeks on an n-3 fatty acid-supplemented diet in which red meat was replaced with lean and fatty fish. At the end of each period, the subjects responded to a 48-hour recall questionnaire, so that we could assess their compliance with the diet, and blood samples were collected for the determination of plasma fatty acids. Stearic fatty acid was significantly decreased after the fish diet. n-7 and n-9 fatty acids showed no significant changes throughout the study. At the end of the 4-week period when the fish diet was consumed, linoleic acid and its long-chain derivative docosapentaenoic acid (22:5 n-6) were significantly increased. The most notable changes in n-3 series fatty acids at the end of the third period were the significant decrease in linolenic acid and the significant increase in its long-chain derivatives eicosapentaenoic (20:5 n 3) and docosahexaneoic acid (22:6 n-3). These changes in plasma fatty acid levels may have beneficial effects on coronary heart disease. PMID- 7872657 TI - Resistance to oxidation of native lipoproteins and erythrocyte membrane lipids in rats with iron overload. AB - Iron plays a promoting role in lipid oxidation through several mechanisms. Therefore, hepatic iron deposits in the rat may lead to peroxidative damage and to alterations in the lipoprotein formation. In this report we observed that an iron overload in rats strongly reduced the hepatic lipoprotein secretion but did not affect oxidation resistance of native lipoproteins and erythrocyte lipids in spite of tocopherol and ascorbate deficiencies. Since oxidation resistance depends on the substrate to antioxidant vitamin molar ratio, our results show that an iron overload probably alters the lipoprotein lipid fatty acid composition in rats. PMID- 7872658 TI - Serum lipids in children with xeroderma from an inland district of Sri Lanka. AB - Children living on plantations in inland districts of the southeastern part of Sri Lanka frequently develop a skin condition on the legs described as mosaic skin or xeroderma. This condition is characterized by atrophic, dry, shining and scaly skin. The etiology is unknown. A food frequency survey indicated a low energy intake, a diet with a low fat content, and anthropometric data have shown a high prevalence of malnutrition within this group. The skin condition brought attention to a possible deficiency of essential nutrients, especially essential fatty acids. In order to investigate the possible association with a deficiency of essential fatty acids, blood samples were collected from both children having signs of xeroderma and controls. The total amount of phospholipids was low, but the fatty acid profile of this lipid class was similar to the controls. A vitamin A deficiency was indicated by low levels of its transport proteins. A multifactorial etiology where vitamin A deficiency may play a role is discussed. PMID- 7872659 TI - Establishment of an in vitro model for cisplatin resistance in human neuroblastoma cell lines. AB - Two unique cisplatin-resistant neuroblastoma (NB) cell lines have been derived from the established lines IMR-32 and SK-N-SH by treatment with escalating doses of cisplatin. IMR/CP.20 was 6.6-fold and SK/CP.15 was 3.8-fold more resistant to the cytotoxic effects of cisplatin than the parent lines. The parent SK-N-SH cells were 16.6-fold more resistant to the effects of cisplatin than IMR-32 cells. The cisplatin-resistant cell lines demonstrated alterations to their morphology, but there was no change in the cell growth characteristics of the resistant compared to the sensitive lines. Cytogenetic analysis revealed that clonal selection of parental subclones had occurred with additional chromosomal changes in both resistant lines. Both IMR/CP.20 and SK/CP.15 lines were cross resistant to aphidicolin and to L-phenylalanine mustard. The IMR/CP.20 line was 7.3-fold more resistant to mitomycin C than the parent line. Neither cisplatin resistant NB line was cross-resistant to 5-fluorouracil, etoposide or doxorubicin. All NB lines had low levels of DNA repair compared to HeLa or CHO-K1 cells. However, the IMR/CP.20 cell line showed a significantly higher ability to effect DNA repair than the parent IMR-32 line, indicating that the increased resistance to cisplatin observed in this line may, in part, be due to an enhanced DNA repair capacity. PMID- 7872660 TI - Prothymosin alpha augments deficient antitumor activity of monocytes from melanoma patients in vitro. AB - Human peripheral blood monocytes derived from normal donors, melanoma patients (MP) before and after chemotherapy (MPa) were assayed for their capacity to inhibit SK-MEL-28 melanoma cell growth in vitro; in addition, growth modulating effects by prothymosin alpha 1 (ProTa) were studied. After preincubation with or without ProTa for 1 day, monocytes were cultured in the absence or presence of interferon-gamma (rIFN-gamma) for a further day, and after cocultivation with SK MEL-28 melanoma cells for 3 days monocyte/macrophage-mediated tumoristatic activity was determined employing the microculture tetrazolium (MTT) assay. The level of baseline growth inhibitory activity of unstimulated MP and MPa monocytes was 22% and 15%, respectively, and was significantly lower (p < 0.001) than that of normal monocytes (35%). The stimulation of monocytes/macrophages by rIFN-gamma greatly elevated the mean of their antitumor activity up to 44%, 49% and 58% in the group of MP, MPa and normal donors, respectively. ProTa significantly increased the level of monocyte-mediated growth inhibition of MP and normal donors, when it was applied alone or in combination with rIFN-gamma. Monocytes of MP at early stages (I and II) of their disease, when incubated with rIFN-gamma, showed a higher increase in tumoristatic activity than at stage III and tended to be the most susceptible to preincubation with ProTa followed by rIFN-gamma activation. However, on average tumoristatic activity of MP/MPa monocytes was significantly lower compared with that of normal monocytes, when activated with rIFN-gamma or ProTa alone or combined. Moreover, no effects on TNF-alpha secretion of MP/MPa monocytes were found by ProTa and/or rIFN-gamma, whereas TNF alpha levels from normal monocytes were significantly increased by the two stimuli. These results indicate that monocyte disorders in melanoma patients may be partially normalized by ProTa. PMID- 7872661 TI - Isolation of a new vinca alkaloid from the leaves of Ervatamia microphylla as an inhibitor of ras functions. AB - A new vinca alkaloid was isolated from a chroloform extract of Ervatamia microphylla leaves as a potent inhibitor of ras functions. The structure of the new alkaloid was elucidated by spectroscopic analysis to be a dimer of aspidosperma-class indoles. The new inhibitor, named III-121C, induced normal morphology in K-ras(ts)-NRK cells at around 0.3 microgram/ml. It also inhibited DNA, RNA, and protein synthesis weakly at 0.3 microgram/ml. It inhibited the growth of K-ras(ts)-NRK cells with IC50s of 0.29, and 0.20 microgram/ml at 33 degrees C and 39 degrees C, respectively. III-121C is the first vinca alkaloid that inhibits ras functions. PMID- 7872662 TI - Induction of apoptosis by transforming growth factor beta 1 in glioma and trigeminal neurinoma cells. AB - Transforming growth factor beta 1 (TGF beta 1) inhibits cell proliferation in T24 glioma and 476-16 trigeminal neurinoma (Schwannoma) cells. In both cell types, the inhibition of cell proliferation is followed by cell rounding and detachment as well as internucleosomal DNA fragmentation, nuclear condensation and cell shrinkage, cellular changes that are characteristic for apoptosis. While the induction of apoptosis is closely coupled with the inhibition of cell proliferation in these tumor cells, the mode of apoptosis appears to differ between the two cell types. In 476-16 cells whose proliferation is highly susceptible to TGF beta 1, apoptosis occurs primarily after growth arrest at the G1 phase. Apoptotic cell death of 476-16 cells pretreated with TGF beta 1 is stimulated by serum deprivation, and it is inhibited by mitogenic growth factors such as insulin and platelet-derived growth factors. In T24 cells whose DNA replication is inhibited only moderately by TGF beta 1, apoptosis occurs in the presence of TGF beta 1 during the final cell division cycle when cells undergo density-induced growth arrest. While staurosporine accelerates TGF beta 1-induced apoptosis in both 476-16 and T24 cells, 12-O-tetradecanoylphorbol 13-acetate inhibits TGF beta 1-induced apoptosis of 476-16 cells but stimulates that of T24 cells. The present results suggest that TGF beta 1 may potentially be utilized for the management of neurogenic tumors of glial and Schwann cell origin. PMID- 7872663 TI - A multiwell assay for inhibitors of phosphatidylinositol-3-kinase and the identification of natural product inhibitors. AB - A convenient and reliable multisample assay for the screening of inhibitors of the growth factor signalling enzyme phosphatidylinositol-3-kinase (PtdIns-3-K) has been developed. Four natural product inhibitors of Ptdlns-3-K have been identified with IC50 values for hypericin 0.18 microM, emodin 3.3 microM, asperuloside 2.0 microM and uttronin A 1.1 microM. PMID- 7872664 TI - Immunostimulation by Alsophila spinulosa extract fraction VII of both humoral and cellular immune responses. AB - Alsophila spinulosa (Cyatheaceae) has been used in Asia as a herbal medicine. In this study, the immunomodulatory effects of Alsophila spinulosa dried stems water extract fraction VII (AS-VII) were studied in vitro using an animal model. The results showed that AS-VII stimulated splenocyte proliferation in both BALB/c and C3H/HeJ mice. By cell fractionation analysis, the results showed that the mitogenic effect of AS-VII was predominantly on B cell population. The antibody response was also augmented by AS-VII in BALB/c and C3H/HeJ mice. The augmentation of immune responses in C3H/HeJ, the lipopolysaccharide (LPS) hyporesponsive mouse strain, indicated that the activity was not simply due to the LPS contamination which may be present in AS-VII preparation. Furthermore, AS VII caused an increase in cytotoxic T cell activity in a mixed lymphocyte reaction culture. These data indicate that AS-VII possesses the capability of augmenting both humoral and cellular immune responses. PMID- 7872665 TI - Expression and release of plasminogen activators, their inhibitors and receptor by human tumor cell lines. AB - Plasminogen activators (PAs) and their inhibitors (PAIs) can be produced by tumor cells and surrounding inflammatory cells and fibroblasts. The present study evaluate both the expression and release of PAs (uPA and tPA) and PAIs (PAI-1 and PAI-2) from cultured cells, and also the expression of uPA receptor (uPAR). Immunocytochemistry showed that PAs, PAIs and uPAR were present to different extents on the surface of colon carcinoma cells (Caco-2, HT-29), malignant melanoma cells (LOX) and normal fibroblasts. uPA immunoreactivity was intermediate in Caco-2, HT-29 and LOX and weak in the fibroblasts. tPA immunoreactivity was intermediate in Caco-2 and LOX and weak in HT-29 and fibroblasts. PAI-1 and PAI-2 immunoreactivities were absent in HT-29, weak in Caco-2 and strong in fibroblasts. In LOX the immunoreactivity was intermediate for PAI-1 and strong for PAI-2. uPAR immunoreactivity was weak in Caco-2, HT-29 and LOX and negative in fibroblasts. ELISAs on conditioned medium detected that the colon carcinoma cells Caco-2 and HT-29 did not release any PAs or PAIs. LOX released tPA (median 9 ng/million cells at 72 hours), PAI-1 (1050 ng/million cells) and PAI-2 (245 ng/million cells), and fibroblasts released uPA (1 ng/million cells) and PAI-1 (910 ng/million cells). These results show that both tumor cells and fibroblasts express tissue destructive enzymes, PAs and PAIs, whereas only the tumor cells express the uPAR required for focalization and regulation of PA activity at the cell surface. The melanoma cells LOX and fibroblasts also released PAs and PAIs, in contrast to the colon carcinoma cells Caco-2 and HT-29. PMID- 7872666 TI - Progesterone receptors are detectable in tumor fragment spheroids of meningiomas in vitro. AB - Progesterone receptors (PgR) are hardly to be found in monolayer tissue culture of meningiomas although 60-70% of native tissue specimens are PgR positive. Thus we examined whether RgR might be detectable in fragment spheroids of meningiomas in vitro. 25 meningiomas of 17 women and 8 men were investigated as native tissue, monolayer cell culture (primary passage and passage 3) and as fragment spheroid culture after 1 and 3 weeks. 18/25 native tissue samples revealed the PgR. There was no prevalence of sex or histological subtypes discernible. PgR was preserved in cell clumps of the primary passage but was completely lost when cells grew as monolayers (primary passage and passage 3). 21 meningiomas formed spheroids in vitro. In 8 out of 15 native PgR positive tumors the fragment spheroids showed PgR on cryosections after 1 and 3 weeks of culture. We conclude that PgR are preserved in a considerable amount of tumor fragment spheroids of meningiomas in contrast to monolayer culture. Thus spheroids seem to be a suitable tool to investigate progesterone/anti-progesterone effects in meningiomas in vitro. PMID- 7872667 TI - Establishment of a human melanoma cell line lacking p53 expression and spontaneously metastasizing in nude mice. AB - Nine human melanoma cell lines established in our laboratory were analyzed for p53 gene expression and their tumorigenic and metastatic potential in nude mice. Northern blot analyses showed that five of the cell lines (55%) had either complete loss or low levels of p53 transcripts. Immunocytochemical analysis for p53 protein expression agreed with mRNA analysis results. Nucleotide sequencing showed no mutations in exons 5 through 8 of the gene. All cell lines except one gave rise to tumors at subcutaneous inoculation sites in nude mice. The melanoma cell line UISO-MEL-6, completely lacking p53 expression, spontaneously metastasized to lung and liver in nude mice. PMID- 7872669 TI - Expression and alterations of CD66 antigen by interferon-gamma in human breast carcinoma cell lines. AB - Monoclonal antibodies of the CD66/67 panel from the 5th Workshop on Leukocyte Antigens bound (as determined by flow cytometry) to the cell surface of human breast carcinoma cell lines BT-20 and MDA-MB-468. The molecular weight of antigenic polypeptides recognized by the CD66 monoclonal antibody F34-187 differed between the two examined breast carcinoma lines as follows: 50kDa, 95 kDa and 130 kDa polypeptides were expressed on both BT-20 and MCF-7 cell lines, while the major 160-180 kDa polypeptide was found only in MDA-MB-468 cells. IFN gamma, all-trans retinoic acid and phorbol ester (TPA) induced up-regulation of CD66 antigen(s) recognized by the monoclonal antibody F34-187 (as determined by flow cytometry). Different alterations of CD66 antigenic polypeptides recognized by F34-187 monoclonal antibody, induced by interferon-gamma and indentified by immunoblotting, were found on BT-20, MCF-7 and MDA-MB-468 breast carcinoma cell lines. PMID- 7872668 TI - Control of DNA replication by protein phosphorylation. AB - Protein phosphorylation is a versatile posttranslational modification and the most eminent molecular mechanism that can regulate enzymatic activities, emergence of cells from quiescence, DNA replication and onset of mitosis, gene expression, nuclear import, development, and memory. The cell cycle is mainly regulated by p34cdc2 in association with cyclins B at G2/M and by Cdk2 in association with cyclins A, D1, and E at G1/S checkpoints. MAP kinases might link the G0 to G1 transition with the regulation of the cell cycle whereas phosphorylation of replication protein factors, c-Myc, AP-1, Oct-1, T-antigen, retinoblastoma, and p53 might link the G1 to S transition with the control of DNA synthesis. These transcription regulators can up- or downregulate DNA replication and their DNA binding activities or transacting properties are controlled by phosphorylation. PMID- 7872670 TI - p53 expression in human pancreatic cancer correlates with enhanced biological aggressiveness. AB - Immunohistochemical analysis of the p53 tumor suppressor gene was performed in 69 human pancreatic ductal adenocarcinomas, using a highly specific anti-p53 antibody. Nuclear immunoreactivity was found in 40 tumors, yielding an overall frequency of 58%. Immunoblotting confirmed that nuclear immunoreactivity was associated with increased p53 protein levels. p53 mRNA levels were increased in 9 of 9 tested cancers, without evidence for gene amplification. Analysis of the immunostaining data by chi-square and log-rank indicated that the presence of nuclear immunoreactivity correlated with a more advanced clinical stage, and a statistically significant decrease in the post-operative survival period. In 12 cancers, metastatic tissue samples were also available for p53 analysis. Nuclear p53 immunostaining in the primary tumors was not always associated with p53 immunoreactivity in the metastatic samples, and metastases occurred in the absence of nuclear p53 immunoreactivity in the primary lesion. These findings suggest that increased p53 protein levels in human pancreatic cancer may be due not only to p53 mutations which attenuate the degradation of the protein but also to an increase in p53 mRNA levels leading to increased p53 synthesis, and that p53 nuclear immunoreactivity in these cancers implies enhanced tumor aggressiveness but is not essential for the development of metastases. PMID- 7872671 TI - The rat Nb2 lymphoma: a novel model for tumor progression. AB - Tumor progression of cancers is manifested by phenotypic property changes including development of hormone/growth factor independence and metastatic ability. The progression results from acquired genomic alterations leading to clonal heterogeneity and outgrowth of more aggressive and therapy-resistant sublines. Previously, a cultured rat "Nb2 lymphoma" cell line was established, whose viability depends critically on the hormone, prolactin, acting as the principal growth factor. By prolactin starvation, prolactin-independent sublines were generated which possessed the parent karyotype plus extra acquired chromosomal changes (clonal evolution). In this study, the parent line (Nb2-U17) and a cloned subline (SFJCD1) were compared for metastatic ability using single s.c. tumor transplants in Noble rats. Rats (22) bearing Nb2-U17 tumors showed no evidence of metastases at autopsy, even when tumors at implantation site reached a size of 9 cm (length + width). In contrast, rats (19) bearing SFJCD1 tumors showed multiple metastases (liver, kidney) when transplants exceeded 5 cm. This difference in metastatic ability may be related to the acquisition of an inversion in chromosome 1, i.e. inv(1)(q31q41). The 1q41 locus is adjacent to the reported H-ras-1 proto-oncogene locus (1q41-q42). In another subline, tetraploidization (flow cytometric analysis, karyotyping) occurred spontaneously following prolonged culturing (20 mo). Together, the parent Nb2 lymphoma line and its clonal derivatives provide a novel system for studying cellular and molecular mechanisms underlying tumor progression to the metastatic phenotype. PMID- 7872672 TI - Pilot study of monoclonal antibody localization in subcutaneous and intracranial lung tumor xenografts after proton irradiation. AB - The purpose of this study was to determine if proton irradiation can increase the localization of radiolabeled monoclonal antibodies (MAb) in subcutaneous (s.c.) or intracranial (i.c.) human lung tumors xenotransplanted in athymic rats. Rats with carcinoembryonic antigen (CEA)-expressing (NCI-H441) tumors were irradiated using 3 different proton time-dose regimens, followed by 111In-ZCE025, an anti CEA MAb, which was injected 2 hr after the last dose of irradiation, and the animals were euthanized 3 days later for biodistribution and other assays. Proton irradiation at 10 gray (Gy) as a single dose or in 2 Gy fractions given on 5 consecutive days increased the uptake of 111In-ZCE025 into s.c. tumors by 292% and 182%, respectively, compared to nonirradiated controls. No enhancement in radiolabeled MAb delivery was seen after hemibrain irradiation in animals with i.c. tumors. Histopathological examination of both implantation sites showed a viable poorly differentiated adenocarcinoma with a decrease in blood vessel density, a decrease in mitotic activity, and an increase in areas of necrosis following irradiation as compared with adjacent nonirradiated tissue. CEA expression was generally maintained in vivo in that the marker was detectable in the tumor, plasma, and cerebrospinal fluid. Oxygen radical production by peripheral blood cells from s.c. and i.c. tumor-bearing rats exhibited strikingly different patterns of responsiveness. I.c. injected animals were 24% lighter than their s.c. injected counterparts, but no neurological signs of tumor progression were noted. The results indicate that proton irradiation can be used effectively to increase the delivery of radiolabeled MAb to s.c. implanted human lung tumor xenografts. However, in order to accomplish this in the brain, other radiation time-dose schedules and treatments may be needed. PMID- 7872673 TI - Overexpression of c-fos induces expression of the retinoblastoma tumor suppressor gene Rb in transfected cells. AB - Hypophosphorylated Rb, the product of the tumor suppressor gene associated with hereditary retinoblastoma, is thought to act as a suppressor of cell growth and proliferation during G1 phase. We investigated whether Rb expression was dependent on the expression level of the immediate early cell growth gene, c-fos, which is transiently expressed as cells re-enter G1 phase from quiescence. To explore the functional relationship between c-fos and Rb, a eukaryotic expression plasmid was constructed containing the c-fos gene under control of the SV40 promoter complex. This plasmid was co-transfected with plasmids encoding pRSV cat and G418 resistance, into HeLa S3 cells, and clonal populations of transfected (RSfos) cells selected. High levels of c-fos expression in transfected cells were confirmed by both western and northern blot. Rb protein content per cell was determined by flow cytometry using an Rb-specific primary antibody and a FITC conjugated secondary antibody. Higher expression of Rb (2-6 fold/cell) in approximately 20% of RSfos transfected cells was observed in comparison to parental HeLa cells. Rb content per cell increased approximately 2-fold during the cell cycle in both parental HeLa cells and RSfos cell clones which overexpressed Rb. Rb accumulation occurred in a manner consistent with normal mass accumulation during the cell cycle. Overexpression of Rb in RSfos cells was also confirmed by western blot analysis. Because one possible function of RB may be to act as a brake on cell growth, it is possible that overexpression of RB acts as an inhibitory counter activity to overexpression of the growth promoting activity of c-fos. This possible balancing activity of Rb was further suggested when Rb protein expression levels were measured in different clonal lines of RSfos transfected cells overexpressing increasing levels of c-fos. Overexpression of Rb was proportional to the level of overexpression of c-fos in each clonal cell line. Such evidence suggests that Rb was proportional to the level of overexpression of c-fos in each clonal cell line. Such evidence suggests that Rb expression may be regulated in a manner which balances the transcription stimulatory effects of c-fos overexpression and its effects on the transcription of other genes during the cell cycle. PMID- 7872674 TI - Evaluation of organoselenium compounds for potential chemopreventive properties in colon carcinogenesis. AB - As a part of a program aimed to develop less toxic and more effective chemopreventive organoselenium compounds than inorganic selenium, we have evaluated benzyl selenocyanate (BSC) and its o-, m-, p-nitro and -methoxy isomers, o-, m-, and p-isomers of phenylenebis(methylene)selenocyanate (XSC), dibenzyl diselenide (DDS), and 2,2'-diselenobis[((N,N-dimethylamino)methyl)- benzene]bis(hydrochloride salt) (DSBDB) for their potential colon tumor inhibitory properties using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF), a preneoplastic lesion, in male F344 rats prior to preclinical efficacy study. In the first experiment, the effect of these agents administered during initiation and postinitiation periods of carcinogenesis was investigated. Male F344 rats were fed diets containing 8 ppm Na2SeO3 or 10 ppm of each BSC and its analogues, DDS and DSBDB or 20 ppm of each XSC analogue, two weeks prior to AOM (15 mg/kg body wt., once weekly for two weeks, s.c.) administration and during and until 8 weeks after AOM treatment. Formalin-fixed and methylene blue stained colons were scored for AOM-induced ACF using the light microscope. Taking body weight gains and multiplicity of 4 or more AC/focus, the inhibitory effects of Na2SeO3, o-, m- and p-methoxy-BSC, p-XSC and DDS were much greater than those of the other selenium compounds. In the second study, the effects of these agents when administered during the initiation or postinitiation periods were investigated. The results indicated that o-, m-, and p-methoxy-BSC, DDS and p-XSC significantly inhibited crypt multiplicity during the initiation period whereas o , and p-methoxy-BSC, p-XSC and DDS suppressed crypt multiplicity during the postinitiation period. It is concluded that o-, and p-methoxy-BSC, p-XSC and DDS possess potential chemopreventive properties in colon cancer. Further studies are warranted to evaluated these agents for chemopreventive properties in preclinical efficacy studies. PMID- 7872675 TI - Effects of 5-fluorouracil derivatives on papillomas induced by application of 7,12-dimethylbenz(a)anthracene in mice. AB - We examined the effects of an application of 5-fluorouracil (5-FU) ointment and a chronic oral administration of 1-(2-tetrahydrofuryl)-5-FU plus uracil (UFT) on 7,12-dimethyl-benz(a)-anthracene-induced squamous cell papillomas in mice. Although application of 5-FU ointment reduced the growth of papillomas slightly, chronic oral administration of UFT could prevent tumorigenesis and suppress the growth of papillomas, resulting in the reduction of the tumorous viability and DNA synthesis. PMID- 7872676 TI - Antitumor activity of hexamethylmelamine on human tumor xenografts serially transplanted in nude mice. AB - The antitumor activity of hexamethylmelamine (HMM) was evaluated using four human tumor xenografts serially transplanted in nude mice. HMM was dissolved in 0.2 ml of 1% hydroxypropyl cellulose per mouse and administered perorally daily, except on Sunday, for 4 weeks, giving an estimated maximum tolerated dose (MTD) of HMM of 75 mg/kg. The MX-1 cell line showed dose-dependent sensitivity to HMM and was completely eradicated by treatment at the MTD. The minimum effective dose of HMM against MX-1 was calculated to be 22.1 mg HMM/kg, resulting in the chemotherapeutic index of 3.4. The demethylated derivatives of HMM, pentamethylmelamine and tetramethylmelamine, were also effective against MX-1, whereas trimethylmelamine was ineffective. The effect of HMM was more marked when the drug was administered on day 1 after tumor inoculation, compared with administration during the exponential growth phase. HMM is thought to be a promising agent for the treatment of several types of human carcinoma, producing active metabolites in vivo after peroral administration. PMID- 7872677 TI - Conjugated system of homo-aza-steroidal esters in cancer chemotherapy. AB - The homo-aza-steroidal esters of conjugated carboxylic derivatives of nitrogen mustards are reviewed. Particularly we discuss the antitumor activity of cinnamic acid and benzoic acid mustard isomers, esters of homo-aza-steroids in which the mustard acid is linked to the C-3 or C17 position, while the lactam nucleus is in the D or A ring of the steroid respectively. The current literature indicates that the potential is due to the synergistic activity of both the steroidal lactam and the mustard of the acids. Steroidal lactams, namely 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam, the isomer 3 alpha hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic- 13,17-lactam, 3 beta hydroxy-13 alpha-amino 13,17-seco-5-androsten-17-oic-13,17-lactam and the 17 beta hydroxy-3-aza-A-homo- 4 alpha-androsten-4-one, have been used as biological platforms of the cinnamic acid, of the benzoic acid mustard isomers and the 4 methyl-benzoic acid mustard. The twelve esters of cinnamic acid mustard isomers were tested against P388, L1210 leukemias Ehrlich ascites tumor (EAT) and melanoma B16 in vivo. The effect of homo-aza-steroidal esters of N,N-bis(2 chloroethyl) amino cinnamic acid isomers on the incorporation of the radioactive precursors into DNA, RNA and proteins of L1210, P388 leukemias, Ehrlich ascites tumor (EAT) and Baby Hamster Kidney (BHK) cells, was investigated. The effect of the homo-aza-steroidal esters of N,N-bis(2-chloroethyl) aminobenzoic acid isomers on the incorporation of radioactive precursors into DNA, RNA and proteins was studied in L1210, P388 leukemias, Ehrlich ascites tumor and Baby hamster kidney cells. PMID- 7872678 TI - Changes in the zonation of lactate dehydrogenase activity in lobules of rat liver after experimentally induced colon carcinoma metastases. AB - Visualization of lactate dehydrogenase (LDH) activity with Neotetrazolium as final electron acceptor under anaerobic conditions and an incubation medium containing polyvinyl alcohol showed that under normal physiological conditions a zonal distribution of LDH activity is present in the liver lobule of male rats. Periportal hepatocytes contain more LDH activity than pericentral hepatocytes. This difference is due to the role of LDH both in gluconeogenesis (periportal cells) and glycolysis (pericentral cells). In livers containing metastases from colon carcinoma, areas of the parenchyma which are not affected by tumour growth maintain such zonation in the lobule, whereas areas close to metastatic foci show increased activity which is distributed uniformly over the lobule. This change may be explained by a Cori's cycle-like relationship between malignant cells and the surrounding hepatocytes due to glucose consumption and lactate production by the tumour cells. Within the metastatic foci, a zonation of LDH activity was also observed. Malignant cells close to the edge of the tumours contained the lowest activity, whereas activity increased inwards. Cancer cells directly surrounding necrotic areas showed the highest activity. Such patterns are in line with increasing anaerobic glycolysis towards the inner metastatic regions. Anaerobic glycolysis supplies limited amounts of ATP with concomitant lactate production but also large amounts of metabolites for RNA, DNA, lipid and complex carbohydrate synthesis. Lactate that is produced by the metastases induces adaptive changes in surrounding hepatocytes to convert this excess of lactate effectively. PMID- 7872679 TI - Selective compartmentalization of different mdm2 proteins within the nucleus. AB - Overexpression of the mdm2 protooncogene protein, which can lead to the inactivation of normal p53, has been observed in some human cancers. The mdm2 gene is positively regulated by p53, providing for a feedback loop in the control of both p53 and mdm2 activity. The expression of the mdm2 and p53 proteins in different non-small cell lung carcinoma (NSCLC) cell types harboring wild-type or mutant p53, or lacking p53 altogether, were investigated to determine whether a correlation exists between the expression of these two proteins. The mdm2 protein was expressed at very low levels in all NSCLC lines examined, regardless of the p53 status. To determine whether mdm2 could be induced by p53 in NSCLC, NSCLC cells were transfected with a recombinant adenovirus expressing high levels of wild-type p53. The highest levels of exogenous wild-type p53 were observed in p53 null H358 and H1299 cells and in H226b cells expressing endogenous wild-type p53 were observed in p53-null H358 and H1299 cells and in H226b cells expressing endogenous wild-type p53. In these cells, wild-type p53 induced the expression of 90/92K M(r) mdm2 proteins, as well as several faster-migrating mdm2-related species exhibiting relative mobilities of 76/78K, 57/59K, 46K, 28K, and 12K. Northern analyses of H358 and H1299 cells transfected with wild-type p53 showed that these cells expressed three species of mdm2 mRNA of 5.5, 4.6-3.8, and 2.1 Kb in size. Subcellular fractionation revealed that the 90/92K M(r) mdm2 protein species was localized to both the crude plasma membrane/cytoplasmic and nuclear fractions, and that the smaller mdm2 proteins associated selectively with different nuclear substructures. The 76/78K, 57/59K, and 46K Mr(r) mdm2 proteins may be derived by differential splicing of the 5.5 Kb mRNA, and their differential compartmentalization within the nucleus suggests that each has a distinct function, potentially in the regulation of p53 and other gene products. PMID- 7872680 TI - Two-dimensional gel analysis of p53-mediated changes in protein expression. AB - The p53 gene product suppresses both tumor cell growth and the cellular transformation process promoted by oncogenes. Although several genes are known to be positively regulated by p53, it is unclear how many gene expression events are involved in p53-mediated growth arrest and apoptosis. Two-dimensional gel electrophoresis was employed to investigate changes in whole-cell protein expression in p53-null H1299 cells that were transfected with a recombinant adenovirus expressing wild-type p53 at high efficiency. The two-dimensional gel analysis was restricted to proteins ranging in mass from 12,000 to 80,000 daltons. A total of 17 proteins were induced and one was repressed within 16 h of expression of exogenous wild-type p53 in H1299 cells. These results indicate that p53-mediated growth suppression involves a complex array of gene expression events. PMID- 7872681 TI - Electron microscopic analysis of the relationship between nuclear matrix stability and cell differentiation. AB - Two cell lines, the less differentiated CC2/CUHK2 and the more differentiated CC3/CUHKE3, were used to study the difference in nuclear matrix stability against DNase 1 digestion. The nuclear matrix was almost totally extracted when the CC3/CUHK3 cells were digested with 100 micrograms/ml DNase 1, while that of the CC2/CUHK2 cells was still present even when 200 micrograms/ml DNase 1 was used. It is suggested that more differentiated cells have a less stable nuclear matrix while the less differentiated ones have a more stable nuclear matrix. The same phenomenon was also observed in normal human and rat cervical epithelia. The nuclear matrix of the poorly differentiated basal cells was more stable than that of the more differentiated superficial cells. This cell differentiation stage dependent stability of the nuclear matrix is probably related to the nuclear activity and gene expression. PMID- 7872682 TI - Paracrine and autocrine regulation of human melanocyte and melanoma cell growth by transforming growth factor beta in vitro. AB - It has been considered that the growth of human melanoma cells is positively and negatively regulated by transforming growth factors. To investigate further the role of transforming growth factor beta (TGF-beta) in melanoma biology, we analysed paracrine and autocrine growth regulatory properties of TGF-beta in normal human melanocytes and malignant melanoma cell lines in vitro. Exogenously added TGF-beta 1 potently inhibited normal melanocyte proliferation and DNA synthesis in all cultures examined; in contrast, TGF-beta 1 inhibited only moderately or not at all the growth of cultured melanoma cells. Melanoma cell lines established from metastatic lesions were found to be less sensitive to TGF beta 1 than those derived from primary melanomas. TGF-beta 1 resistance correlated with high levels of active TGF-beta secreted by metastatic cell lines. Inactivation of endogenously produced TGF-beta by neutralizing anti-TGF-beta antibody resulted in the stimulation of cell proliferation of a TGF-beta sensitive primary melanoma cell line but not of a resistant metastatic one. These findings suggest that TGF-beta may function as a paracrine and autocrine growth inhibiting factor in the growth regulation of human melanocytic cells. The gradual loss of response of melanocytic cells to TGF-beta during malignant progression suggests that escape of melanoma cells from growth regulation by TGF beta could be involved in melanoma oncogenesis. PMID- 7872683 TI - Role of tissue factor in the antitumor effect of recombinant human tumor necrosis factor-alpha in mice. AB - Recombinant tumor necrosis factor-alpha (rTNF-alpha) inhibited tumor growth of Meth A fibrosarcoma (Meth A) solid tumor in mice, and the antitumor effect of rTNF-alpha was significantly decreased by pretreatment with small doses or rTNF alpha in mice. In in vitro experiments, incubation of human umbilical vein endothelial cells with rTNF-alpha enhanced procoagulant activity (PCA), which was drastically augmented after an addition of the conditioned medium of Meth A tumor cells. Furthermore, rTNF-alpha-induced PCA was decreased by pretreatment with rTNF-alpha in endothelial cells. This PCA was completely blocked after the addition of anti-human tissue factor (TF) murine monoclonal antibody. These results imply that in vivo antitumor effects of rTNF-alpha are mediated by expression of TF in endothelial cells, which is augmented by tumor released factor(s). PMID- 7872684 TI - Reactivity of a mouse/human chimeric anti-GM2 antibody KM966 with brain tumors. AB - With the aim of investigating the passive immunotherapy of brain tumors, we examined the binding of a mouse/human chimeric anti-ganglioside GM2 antibody KM966 to various organs and brain tumors. Frozen sections of 51 surgically resected brain tumors were stained with antibody KM966. Fourteen gliomas out of 16 were stained positively with antibody KM966. Eleven positive sections demonstrated homogenous staining. No specific binding to normal gray matter and white matter was observed. Some cases of meningiomas, neurinomas and metastatic brain tumors were stained with KM966 but with less frequency and intensity than gliomas. In addition, KM966 demonstrated strong antibody-dependent cellular cytotoxicity against human malignant glioma cells. These results showed that antibody KM966 will be useful for passive immunotherapy of malignant gliomas. PMID- 7872685 TI - Stability of ras oncogene mutation in the human tumor xenografts through serial passages. AB - We examined the Ki-ras oncogene point mutation in primary tumors and tumor xenografts as a marker of genetic stability. We detected point mutations at codon 12 of the Ki-ras oncogene in 21.3% (17/80) of the tumor xenografts as well as 21.0% (17/81) of the primary human neoplasms. The mutation from GGT (glycine) to GAT (aspartic acid) was the most frequent mutation in the tumor xenografts (64.7%, 11/17) as well as in the primary human neoplasms (64.7%, 11/17). The point mutation at codon 12 of the Ki-ras gene showed no discrepancy between the original human neoplasms and their xenografts in all 19 cases. The findings suggested that the point mutation at codon 12 of the Ki-ras gene was very stable in human neoplasms and their tumor xenografts through serial transplantation. PMID- 7872686 TI - Effects of vinblastine, colchicine, and verapamil on rhodamine 123 accumulation in human P-glycoprotein-positive leukemia cells. AB - Multidrug-resistant (MDR) cells have been characterized by reduced accumulation of rhodamine 123 (R123). We addressed the question of whether R123 could compete with substrates or inhibitors (vinblastine, colchicine, verapamil) of P glycoprotein (Pgp) overexpressed in MDR cells, using fluorescence image cytometry. Verapamil caused a dose-dependent increase in R123 accumulation. R123 accumulation was increased by vinblastine only at high levels and colchicine had no effect on R123 accumulation. Treatments with two drugs altered R123 accumulation depending on drug concentration ratio. The results indicate that vinblastine, R123 and verapamil can compete for outward transport by Pgp. A dual effect of vinblastine suggests that vinblastine can activate Pgp at low concentrations and inhibit R123 transport at higher concentrations. PMID- 7872687 TI - Role of cytochrome P-450 isoenzymes in the bioactivation of hydroxy anthraquinones. AB - The reductive and the P-450-dependent oxidative bioactivation of various anthraquinones (AQs), 1-hydroxy AQ, 1,2-dihydroxy AQ, 1,4-dihydroxy AQ, 1,8 dihydroxy AQ, 1,2,4-trihydroxy AQ, 1,4-dihydroxy 6-carboxy AQ and 1,8-dihydroxy 3 carboxy AQ, were investigated using purified enzymes, subcellular fractions and four Chinese hamster V79 cell lines lacking and expressing cytochrome P-450 oxidative enzymes. The reduction of AQs performed by NADH-dehydrogenase, NADPH cytochrome P-450 reductase, homogenates and microsomes of V79 cells, indicated that only the carboxy-containing drugs were fairly good superoxide anion stimulators. The P-450 dependent oxidation of AQs, assayed as NADPH consumption with microsomes and reconstituted enzymic systems, demonstrated that the P-450 1A1 and 1A2 were, as expected, the most active catalysts. However, they appeared to catalyze the formation of polyphenols rather than arene oxides or phenoxy radicals. Further support to the lack of generation of reactive intermediates during the oxidative metabolism of AQs came from the genotoxicity studies. In the three V79 cell lines expressing rat cytochrome P-450 1A1, 1A2 and 2B1, AQs did not significantly enhance the sister chromatid exchange induction above that elicited in the parental V79 line. Thus the present results, collectively taken, suggest that the P-450-mediated oxidation pathway plays a minor role in the bioactivation of AQs. PMID- 7872688 TI - Multidrug resistance phenotype evaluation by immunofluorescence and functional tests: comparison of two monoclonal antibodies and three fluorescent dyes in three cells lines. AB - Various agents have been shown to enhance drug sensitivity of multidrug resistant (MDR) cells and are thus of interest when the MDR phenotype is identified. Detection of MDR cells is of importance and can be carried out either by immunofluorescence with monoclonal antibodies or by functional tests using fluorescent dyes uptake. MDR has been analysed by flow cytometry on three sensitive and resistant cell lines, with MRK16 and C219 monoclonal antibodies directed against P-glycoprotein (P-gp) and with rhodamine 123, Hoechst 33342 and daunorubicin. Resistant cells were revealed by MRK16 and C219 but the results obtained with MRK16 gave higher both percentages of fluorescent cells and mean fluorescence. Fluorescence intensity observed with daunorubicin was lower than with rhodamine 123. With Hoechst 33342, mean fluorescence was quite identical on sensitive and on resistant cells. It was concluded that MRK16 and rhodamine 123 were well adapted to detect P-gp and evaluate its functional ability. PMID- 7872689 TI - In vivo modulation of cisplatin cytotoxicity by the cholecystokinin antagonist MK 329 in human pancreatic cancer xenografts. AB - We have previously reported that the cholecystokinin antagonist MK-329 (also known as L-364,718 or devazepide) synergistically enhances sensitivity to cisplatin (DDP) in MIA-PaCa2 human pancreatic cancer cells in tissue culture. In this study, we examined the ability of MK-329 to modulate DDP sensitivity in vivo using MIA-PaCa2 pancreatic cancer xenografts growing subcutaneously in athymic nude mice. Twenty-four hours after tumor inoculation, mice received either DDP intraperitoneally, MK-329 subcutaneously, both DDP and MK-329 or drug vehicles alone. Both DDP and MK-329 alone caused a reduction in the rate of tumor growth. The combination of DDP and MK-329 resulted in enhanced tumor growth delay compared to DDP or MK-329 treated mice. Although MK-329 alone was not nephrotoxic, the addition of MK-329 to DDP treatment resulted in a significant increase in weight loss and nephrotoxicity compared to mice treated with DDP alone; this was reflected by an increase in the plasma BUN levels. Although we believe that the enhanced anti-tumor effect of DDP/MK-329 combination therapy may be independent MK-329's capability to block CCK receptors, the role of CCK receptor blockade in potentiating DDP-induced nephrotoxicity less clear. PMID- 7872690 TI - An in vitro and in vivo study of antitumor effects of genistein on hormone refractory prostate cancer. AB - Hormone refractory prostate cancer remains an incurable disease. Newer agents with more activity are required. Genistein is a flavone compound with anti-tumor activity against various tumor systems in vitro. This study is undertaken to assess the efficacy of genistein against hormone refractory prostate cancer. In vitro, genistein appears to be cytotoxic to both the rat prostate cancer cell line MAT-LyLu and the human prostate adenocarcinoma cell line, PC-3. In vivo, however, genistein failed to significantly inhibit the growth of subcutaneously implanted MAT-LyLu cells. More information regarding the pharmacokinetics and bio availability of genistein is needed to determine if this is an active agent in human metastatic prostate cancer. PMID- 7872691 TI - The activity of topoisomerases is related to the grade and stage in human renal cell carcinoma. AB - Human renal cell carcinomas are quite resistant to chemotherapy. There are no good anticancer agents effective for this disease. Recently, many anticancer agents were found to act as topoisomerase inhibitors and this is closely correlated with their anticancer activity. To assess the efficacy of anticancer agents as topoisomerase inhibitors on renal cell carcinomas, we examined the activity of topoisomerase I and topoisomerase II in 60 primary human renal cell carcinomas using DNA relaxation or DNA decatenation. Significant topoisomerase I and topoisomerase II activities were observed in 39(65%) or 22(36.7%) cases respectively. Topoisomerase II positive cases were more frequent in higher grade cancers (p < 0.01). The topoisomerase I positive rate did not differ in all grades. Our results showed that human renal cell carcinomas had significant topoisomerase I or topoisomerase II activities that were targets for some topoisomerase inhibitors. Therefore these agents could be good candidates for the chemotherapy of human renal cell carcinomas. PMID- 7872692 TI - Exercise training and mouse mammary tumour metastasis. AB - The present study was designed to address whether exercise influences the experimental metastasis of a mouse mammary tumour; a related issue was the impact of timing of exercise onset relative to tumour exposure on NK and LAK mediated cytotoxicity. After 8 weeks of forced treadmill exercise or voluntary wheel running or remaining sedentary, female BALB/c mice received an intravenous (i.v.) injection of female BALB/c mice received an intravenous (i.v.) injection of MMT line 66 tumour cells. Mice were then randomized into continuation of activity (TT, WW), cessation of activity (TS, WS), initiation of activity (ST, SW) and maintenance of sedentary condition (SS) for three weeks. Tumour control (TC) mice, who were matched to the SS mice for age, received an i.v. injection of heat killed MMT 66 tumour cells. In total there were 8 groups including the tumour control. The average number of lung tumours did not differ by activity condition; however, the mice in the continuous treadmill group (TT) tended to have a higher tumour multiplicity (162 +/- 22) and those in the treadmill x sedentary condition (TS) tended to have lower tumour multiplicity (109 +/- 16) compared with the other groups except the SW group (95 +/- 15). The lymphokine activated killer activity in the spleen was significantly elevated in the TS (49 +/- 3%) and WS (44 +/- 3%) mice compared with the sedentary animals (30 +/- 3%) (p < 0.003 and 0.05, respectively). NK activity was lower in the mice that had stopped exercising (TS and WS) after injection of tumour compared with sedentary animals. These data suggest that although exercise training influences natural immune cytotoxic mechanisms in vitro, this may not translate into clinically significant changes in tumour burden. The dissociation between natural immunity and tumour outcome may reflect the relative resistance of the tumour line to lysis by natural killer cells. It remains to be tested if infusion of IL-2 (to induce LAK activity) in exercise trained animals results in fewer tumour metastases. PMID- 7872693 TI - Effects of amino and imino acridines on tumor necrosis factor production by human leukocytes. AB - Tumor necrosis factor (TNF) is a multifunctional cytokine with diverse effects on different cells and tissues. The biological activity of TNF is described on the basis of its cytotoxic action in vivo and in vitro. Different acridines were systematically synthesized and their effects were tested on endotoxin and Staphylococcus aureus-induced TNF production by human leukocytes. 9 aminobutylacridine and 9-ethylaminoacridine totally abrogated the TNF production of leucocytes at a concentration of 3.5 microM, whereas 9-imino -10-butylacridine and 9-imino-10-ethylacridine exerted only a 50% inhibition in the same concentration. Derivatives designated as 9-amino-(2-dimethylamino-ethyl)-acridine and 9-imino-10-(2-dimethylamino-ethyl)-acridine in a concentration of 7 microM exerted only a 30% and a 10% inhibition respectively. A significant modulation of TNF production was not observed when other alkylated derivatives in this series were applied. The TNF-mediated cytotoxic effect of monocytes against WEHI cells was also reduced by the most effective compounds. The acridines did not interfere with the expression of CD 14 molecules on monocytes. The exact mechanism of the suppression of TNF synthesis by acridines remains to be elucidated, but might be useful in the screening and evaluation of their anticancer properties and antimalarial effects. PMID- 7872694 TI - A model for sensitivity determination of anticancer agents against chemically induced colon cancer in rats. AB - Chemically-induced colon cancer was used to test the sensitivity of tumors to chemotherapeutic agents. Seventy-one Sprague-Dawley rats received dimethylhydrazine (20mg/kg) s.c. once weekly for 20 weeks to induce colon cancer. Then a barium enema was performed to see the size of colon tumors. The animals were divided into three groups that were subjected to the following treatments: 5 fluorouracil (5 FU); 1-(2-tetrahydrofuryl)-5 FU(FT); and a mixture of FT and uracil (UFT). After 5 weeks of treatment, the barium enema was repeated. "Response" was assessed on the basis of tumor doubling time. Response rates in the 5-FU, FT, and UFT groups were 25%, 33% and 36%, respectively and this reflects the clinical data of these drugs. The present system may be a predictive model for screening anticancer drugs for human colorectal cancer. PMID- 7872695 TI - Combined activity of interleukin-1 alpha or TNF-alpha and doxorubicin on multidrug resistant cell lines: evidence that TNF and DXR have synergistic antitumor and differentiation-inducing effects. AB - We report on the antiproliferative effects that interleukin-1 alpha (IL-1) or TNF alpha (TNF) in combination with doxorubicin (DXR) exert on DXR-sensitive (B16 melanoma, Friend, K562 and CCRF/CEM leukemias) and -resistant (B16-DXR, FLC-DXR, K562-DXR) cell lines in vitro. Multidrug resistance (MDR) of the latter lines entails cross-resistance to vincristine and overexpression of P-glycoprotein. Il 1 showed only a very marginal growth inhibitory activity and the effects of its combination with DXR were essentially additive in all the cell lines, except in chemosensitive B16, where a slight synergism occurred. TNF demonstrated greater antiproliferative activity in the MDR B16 and Friend tumors than in their parent variants. The combination of TNF and DXR produced synergistic growth inhibition in B16, K562 and, particularly, also in the MDR sublines of these two tumors. In addition, TNF and DXR induced synergistically erythroid differentiation in K562 and multidirectional differentiation in K562-DXR. The synergism was critically schedule-dependent in that it was achieved only when DXR application preceded or was simultaneous with that of TNF. Finally, TNF did not modify drug accumulation and retention in the cells. Our present findings stress especially the fact that DXR and TNF may exert useful antitumor synergism even in MDR lines; however, it is not likely that their interaction will occur at the specific MDR process level. PMID- 7872696 TI - ras-induced neoplastic transformation and sensitivity to tumor necrosis factor. AB - Tumor necrosis factor (TNF) is toxic to many tumor cells but not to normal cells. We previously reported that transfection of TNF-resistant C3H10T1/2 fibroblasts with a mutant Ha-ras oncogene induced tumorigenicity as well as TNF sensitivity. To investigate the relationship between tumorigenic transformation and TNF sensitivity, we isolated TNF-resistant revertants from Ha-ras transformed TNF sensitive cells and analyzed them for p21 expression and tumorigenic potential. The TNF-resistant cells expressed the same amount of mutant p21 as TNF-sensitive cells and retained their tumorigenic potential. In fact, TNF-resistant cells were more tumorigenic than TNF-sensitive cells. These results suggest that mutant p21 expression is directly associated with tumorigenic transformation, while acquisition of TNF sensitivity is incidental to the process of neoplastic transformation. It is possible, however, that ras-induced TNF sensitivity and transformation are regulated by different effector molecules downstream of Ras. PMID- 7872697 TI - An essay on the nature of hormonal codes involved in the genesis of human neoplasias (review). AB - We have long been occupied with the motion that the steroid generating system plays a key role as the intermediator between the outer environment and the vulnerable host in the course of carcinogenesis. The purpose of this review article is to rebuild the concept of hormonal carcinogenesis in the light of the developmental flow of endocrinological oncology. Our discussion places much emphasis on the investigation of a number of puzzles surrounding the hormonal signal transmission system in humans as well as in non-human animals. The usefulness of the steroid-responsive enhancer gene/protooncogene complex model was confirmed in the construction of a unifying theory involving chemical carcinogenesis, viral carcinogenesis and hormonal carcinogenesis. We present evidence to suggest that our unifying theory surrounding the hormone-gene relationship is applicable to the genesis of human neoplasia in general, and that members of the human cancer family are interfering with each other in their risk variations in time and space. The nature of steroid substance as the signal transmitter is discussed from the point of view of paleontological endocrinology. PMID- 7872699 TI - Immune control of neoplasia by adoptive transfer of macrophages: potentiality for antigen presentation and gene transfer. AB - Human macrophages could be differentiated from mononuclear precursors present in the blood circulation. After IFN-gamma activation, they became antitumoral and adhered to transformed cells. Low amounts of activated macrophages (MAK) caused regression of experimental tumors in animal models. In cancer patients, MAK were well tolerated and caused tumor necrosis but no clear therapeutic response has been reported up to now. Improvements can be expected using local treatment and more specific macrophages presenting tumor antigens. This restoration of immune recognition of growing tumors with low levels of reactants should ultimately reestablish, after exogenous stimulation, the insufficient immune response of the host against a malignant tumor. Antitumoral macrophages can also be optimized by gene transfection. Macrophages are proposed as stable and long lasting cell vectors for adoptive gene treatments. PMID- 7872698 TI - The genotoxicity of the chloroethylating agent mitozolomide is enhanced in CHO mex+ cells by the administration of antimessenger oligonucleotide targeted against methylguanine-DNA methyltransferase gene (MGMT). AB - The alkylating drug resistance is frequently related to the DNA repair activity 0(6)-alkylguanine-DNA alkyltransferase (0(6)-AT), a protein coded by the methylguanine-DNA methyltransferase gene (MGMT). We synthesized one antisense oligodeoxyribonucleotide (AS-ODN) targeted against the mRNA of the MGMT gene. The administration of this "antimessenger" sequence to a Chinese hamster ovary cell line, expressing the transfected human MGMT gene, caused a moderate decrease of the resistance to the chloroethylating drug mitozolomide (MTZ), measured as induction of sister chromatid exchanges (SCE). The AS-ODN administration combined with depletion and recovery of 0(6)-AT by 0(6)-methylguanine inhibitor treatment showed an enhancement of SCE induction. The results support the inhibition of the MGMT translation mechanism by AS-ODN and suggest that the pre-existing protein could compromise the reversion of the resistant phenotype if is still active during the administration of the "antimessenger" sequence. PMID- 7872700 TI - Thymidylate synthase levels in tumor biopsies from patients with colorectal cancer. AB - Catalytic activity and FdUMP binding characteristics of thymidylate synthase (TS) were determined in 22 tumor biopsies of patients to be treated (15) or just treated (7) for colorectal cancer with 5-fluorouracil and leucovorin. In 19 samples both parameters could be determined and were found to represent a wide range (15-20 fold). High values of activity correlated with no response, but low values of binding or activity were found in responders as well as in non responders. It is concluded that the determination of parameters related to TS function is feasible in tumor biopsies and its relevance for clinical management deserves further study. PMID- 7872702 TI - Lacidipine and josamycin: two new multidrug resistance modulators. AB - In this paper we report the results obtained treating a multidrug resistant (MDR) murine erythroleukemia cell line with daunomycin (DNM) in association with two new modulators characterized by a favourable therapeutic index, lacidipine (LCD), a dihydropyridine calcium antagonist, and josamycin (JSM), a macrolide antibiotic. LCD and JSM exhibited a greater MDR reversal activity than verapamil (VRP) and erythromycin (ERY) respectively. The accumulation of DNM in the DRTL cells exposed to modulators was similar to that of the parental cell line FLC. In the case of LCD, it was possible to ascertain that at a very low concentration this molecule can circumvent MDR without modifying DNM accumulation, suggesting that multiple different determinants may be responsible for MDR other than P-170 in this cell line. PMID- 7872701 TI - Oral cyclophosphamide and oral hydroxyurea in the treatment of hormone refractory prostate cancer in rats. AB - Hormone refractory prostate cancer is a fatal disease and currently no standard cytotoxic chemotherapy exists for prostate cancer. The recent use of prostate specific antigen as an endpoint for clinical trial has resulted in the ability to test the activity of chemotherapy agents in a quick manner. The aim of this study was to investigate the activity of the oral combination of two familiar agents, cyclophosphamide and hydroxyurea, against hormone refractory prostate cancer. In vitro studies demonstrated that hydroxyurea was more active than cyclophosphamide against the anaplastic Dunning rat prostate cancer cell line, Mat-LyLu. In vivo experiments, however, demonstrated cyclophosphamide to be superior to hydroxyurea. The combination of both agents failed to enhance inhibition of subcutaneously implanted Mat-LyLu cells. A human trial of oral cyclophosphamide using prostate specific antigen as an intermediate endpoint may be warranted. PMID- 7872703 TI - Immunotherapy by BCG against prostate adenocarcinomas in anatomical compartments. AB - The prostate adenocarcinoma-III (PA-III) cell line manifests a high rate of metastasis from the SC tumor site through lymphatic channels to the lungs in which they produce visible focal tumors. i.v. inoculation of BCG interfered with the passage of PA-III cells to the lungs; but not if the BCG was inoculated IP. IP inoculation of BCG suppressed propagation of PA-III cells in the peritoneal cavity, but there was no effect on metastasis of PA-III cells from a SC PA-III tumor to the lungs. Inoculation of BCG did not induce a systemic anticancer effect unless PA-III cells and BCG occupied the same anatomical compartment. Two compartments are described: intravascular and intraperitoneal. PMID- 7872704 TI - Synthesis and preliminary in vitro cytotoxicity evaluation of 1,3-bis-(2 propynyl)-1-nitrosourea (BPNU) and derivatives. AB - The in vitro cytotoxicity and differential cellular sensitivity of a series of new N1-(propargyl) nitrosourea derivatives, including 1,3-bis-(2-propynyl)-1 nitrosourea (BPNU), a carmustine (BCNU) analog, were determined in the National Cancer Institute's primary antitumor drug screen. BPNU has a level of cytotoxic activity comparable to BCNU, CCNU and Methyl-CCNU. Unexpectedly, the bi substitution of BPNU at the amino N3 position produced an inactive compound. Compared to BCNU, BPNU has a marked specificity towards leukemic cells and could potentially be useful as an anti-leukemic agent. In this series, the N1 (propargyl) group seems to induce cell line specificity. PMID- 7872705 TI - Lack of expression of a 31/33kD surface protein on human colon carcinoma cells is a marker for metastasizing potential. AB - Two highly metastatic human tumor cell lines, SLU-M1 SLU-M2, were established by in vivo selection in Balb/c-nu/nu mice of SLU-1 xenotransplants derived from an adenocarcinoma of the sigmoid colon. Metastatic spread was screened by transplantation of tissues from various organs of s.c.-tumor-bearing nu/nu mice. A monoclonal antibody, mab ME6H2, prepared against a membrane fraction of HT29 cells, also derived from an adenocarcinoma of the colon, showed high 125I-mab ME6H2 binding only to HT29 and SLU-1 cells, whereas hardly any binding was recorded for SLU-M1 and SLU-M2 cells. All cells of the HT29 and SLU-1 populations exhibited a positive immunofluoresence (IF) but only 1-5% of the SLU-M2 and 10 15% of the SLU-M1 subpopulation. A number of other tumor cell lines did not express the ME6H2 target antigen except for line MCF7, derived from an adenocarcinoma of the breast, which showed an IF positive reaction of 100% of the cells but only 25% of mab binding compared to HT29 and SLU-1 cells. The data indicate that expression of the ME6H2 target antigen is adenocarcinoma-specific and lack of expression is a marker for the metastatic potential of these cells. Mab ME6H2 was rapidly internalized upon binding to viable HT29 cells, resulting in an enhancement of cell growth in vitro and tumor growth in vivo. The mab ME6H2 defined target antigen was isolated from cell lysates by antibody affinity chromatography and was identified as a double band in SDS-PAGE with 31kD and 33kD molecular mass usually present in equal amounts. PMID- 7872706 TI - Production and characterization of monoclonal antibodies against a human ovarian teratocarcinoma cell line. AB - Nine monoclonal antibodies (MAbs) of a total of 125 clones selected by an enzyme immunoassay (ELISA) were produced against a human ovarian teratocarcinoma cell line. Within the panel, one antibody (4E3) has shown a close reactivity to OC 125. However, the antigen recognized by 4E3 was found to be different from the CA 125 antigen. The cell surface antigen recognized by 4E3 has a molecular weight over 2 x 10(6) Da and is highly glycosylated as shown by the periodic acid/Schiff reagent. PMID- 7872707 TI - Scavenging effects of hemoglobin and related heme containing compounds on nitric oxide, reactive oxidants and carcinogenic volatile nitrosocompounds of cigarette smoke. A new method for protection against the dangerous cigarette constituents. AB - The present study refers to the utilization of hemoglobin and related heme containing substances in scavenging noxious compounds contained in the gas phase of cigarette smoke (e.g. nitric oxide (NO), nitrogen oxides (NOx), hydrogen peroxide (H2O2), carbon monoxide (CO), aldehydes, trace elements and carcinogenic nitrosocompounds) which were up to today insufficiently retained by conventional cigarette filters. Hemoglobin impregnated conventional cigarette filters were capable of withholding the above noxious components of the cigarette smoke up to 90%. Similar results were also obtained when solid hemoglobin was sandwiched between two common filters so that all cigarette smoke drawn through the filter comes into contact with the active groups of the hemoglobin molecules (Fe3+, Fe2+, -SH, -NH2). The present study also shows that noxious oxidants contained in cigarette smoke can be retained and neutralized by appropriate scavengers like: a) substances which contain stereospecifically bound iron, b) substances which contain porphyrin ring with iron (e.g. protoporphyrin), c) substances which contain porphyrin ring that does not necessarily contain iron, d) substances which contain porphyrin ring complexed with other metals (e.g. Cu2+, Mg2+). We have also demonstrated that rat alveolar macrophages challenged by cigarette smoke release both superoxide (O2-) and NO the interaction of which resulted in the formation of peroxynitrite (ONOO-). Alveolar macrophages continue to release NO/ONOO- for 30 min following two or three puffs of smoke. Similar results were also obtained in experiments with human volunteers. It was shown that during cigarette smoking the ratio of NO/ONOO- in the inhaled smoke was 1:0.5 while in the exhaled smoke was 1:9, due to secondary redox reactions taking place in the lung resulting in the ONOO- formation. When smokers inhaled cigarette smoke passed through a conventional filter containing hemoglobin, a 70% reduction of both NO and ONOO- in their exhaled cigarette smoke was observed. All findings prove conclusively that, alveolar macrophages exposed to cigarette smoke evoke a dramatic increase of NO, NOx, ONOO- and H2O2 inside the lung. These substances stimulate by a positive feed back mechanism the alveolar macrophages and perhaps even endothelium of the alveolar vessels, to produce more oxidants resulting in lung damage. PMID- 7872708 TI - Effect of proton pump inhibitor on cell growth and sensitivity to cis diamminedichloroplatinum(II) in non-small cell lung cancer cell lines. AB - Recently, the importance of the potassium pump in the cellular accumulation of cis-diamminedichloroplatinum(II) (CDDP) has been reported. In this study we evaluated the role of the proton pump as a determinant of the sensitivity to CDDP in non-small cell lung cancer cell lines in vitro by using a selective proton pump inhibitor, AG-2000. PC-9 and PC-9/CDDP cell lines, which are sensitive or resistant to CDDP, were used for these experiments. PC-9/CDDP was 17.4-fold more resistant to CDDP than PC-9 cells. Relative resistance was not altered by co incubation with a non-cytotoxic dosage of AG-2000. From these studies, it was shown that the proton pump inhibitor AG-2000 did not enhance the sensitivity to CDDP. However, as AG-2000 is not cytotoxic and does not compromise the CDDP sensitivity in NSCLC cells at the concentration of clinical use for gastroduodenal ulcer, AG-2000 can be used with CDDP in chemotherapy for lung cancer. PMID- 7872709 TI - SMS 201-995 in the treatment of refractory prostatic carcinoma. AB - The long-acting synthetic somatostatin analog, SMA 201-995, was used to treat patients with advanced hormonal-refractory prostate cancer. Twenty-two of 24 study patients treated are evaluable for toxicity and 20 are evaluable for response. The dose of SMS 201-995 was 100 mg subcutaneously every 8 hours for 6 weeks. Two patients suffered intolerable gastrointestinal complications requiring early cessation of therapy. No patient had objective evidence of tumor regression. After developing a clinical suspicion that tumor growth accelerated with SMS 201-995, we observed 10 patients closely for 2 months before beginning SMS 201-995 treatment and for the first 2 months on the therapy. In these 10 patients, the serum prostatic acid phosphatase level rose at an accelerated rate after 1 to 2 months of treatment. Among the 20 patients treated and evaluable for response, new osseous metastases developed in 12 and new visceral metastases in 4; 1 developed disseminated intravascular coagulation and 2 developed neurologic complications (mean time to objective progression, 5.6 weeks). Six patients received salvage chemotherapy after disease progressed on SMS 201-995 therapy, 5 of whom have achieved objective tumor regressions. We believe SMS 201995 stimulates prostatic tumor growth and may sensitize tumor cells to subsequent chemotherapy. PMID- 7872711 TI - Response of adenosquamous carcinoma of the pancreas to interferon-alpha, tumor necrosis factor-alpha and 5-fluorouracil combined treatment. AB - A 48-year-old woman with a nonresectable pancreatic tumor received combination chemotherapy with cytokines (IFN-a plus TNF-a) and 5-FU. Since partial response was confirmed after seven months, she underwent re-exploration, and received a pancreatico-duodenectomy. Histologically, the tumor was an adenosquamous carcinoma of the pancreas. She recovered uneventfully. However, the tumor rapidly recurred, and she died five months after surgery. Despite the poor result, the survival of the patient with advanced pancreatic cancer for twelve months after the staring of the treatment suggests that combined chemotherapy with cytokines and 5-FU may be a therapeutic modality for advanced pancreatic cancer. PMID- 7872710 TI - Flow cytometric DNA and p53 analysis in superficially infiltrating bladder carcinoma. AB - Mutations in the p53 gene occur frequently in bladder cancers. Better prognostic factors are needed to help select appropriate treatment for patients with TCC stage T1. Paraffin-embedded tumors from 73 patients with TCC stage T1 were processed for two-parameter flow cytometry, measuring both p53 protein and DNA. There were no statistically significant differences between the WHO grades with respect to p53 protein staining. Furthermore, there were no statistically significant differences between diploid, tetraploid and aneuploid tumors regarding content of mutant p53 protein. Neither were any statistically significant differences observed when ploidy and WHO grade were grouped together. Progression of disease was not correlated with positive p53 protein staining. These results indicate that mutant p53 protein cannot be used as a prognostic factor in TCC stage T1. PMID- 7872712 TI - Reduced nonspecific steroidal esterase activity in human malignant tumor tissue from liver, colon and breast when compared to peritumoral and normal tissue levels. AB - The levels of a nonspecific steroidal esterase estimated as alpha naphthyl acetate esterase (ANAE) activity were measured in apparently normal (peritumoral) tissue of liver, colon and breast cancer patients, in malignant tumor tissue from the same patients and in normal colon tissue from healthy individuals who never had colon cancer. Cancer tissue from all three organs showed 35-79% reduced levels of ANAE activity when compared to peritumoral tissue of the same organ (p < 0.03). When ANAE activity of normal colon tissue from healthy individuals who never had colon cancer was compared with peritumoral colon tissue from colon cancer patients, which were combined with colonic biopsies from cancer-free patients previously operated on for colon cancer, a 50% reduced ANAE activity was observed in these tissues compared to the normal (p < 0.005). A highly significant reduction of enzyme activity was also found when malignant colon tissue from the cancer patients was compared to normal colon tissue from healthy individuals who never had colon cancer. PMID- 7872713 TI - Lymphatic advancement to peritoneal dissemination and liver metastasis in gastric cancer patients. AB - Lymph node metastasis is a risk factor for the occurrence of peritoneal dissemination and liver metastasis in patients with gastric cancer. We analysed data on 893 Japanese patients with serosally invasive gastric cancer, with respect to the relation between lymph node metastasis and peritoneal dissemination or liver metastasis. All these patients were treated in our clinics. Lymph node metastasis was evident in 746 patients, and in these patients the tumors were larger, lymphatic and vascular involvement were prominent and rates of peritoneal dissemination and liver metastasis were higher. In 147 patients with no evidence of lymph node metastasis, peritoneal dissemination was seen in 3.4% of cases and there was no liver metastasis. In cases of peritoneal dissemination and in those with liver metastasis, the rate of lymphatic involvement was higher than when there was vascular involvement. Peritoneal dissemination and liver metastasis are likely to be concomitant with lymph node metastasis in cases of serosally invasive gastric cancer. It seems apparent that lymphatic spread leads to peritoneal dissemination and liver metastasis in patients with gastric cancer. PMID- 7872714 TI - p53 expression and poor prognosis in childhood acute lymphoblastic leukemia. AB - Ninety-one children with untreated acute lymphoblastic leukemia (ALL) were analysed for expression of p53 using immunocytochemistry. p53 expression was found in 80% of the cases by Mab 421. Kaplan-Meier estimates show that patients with p53-positive leukemic cells had significantly shorter survival times under chemotherapy than those with p53-negative leukemic cells (p = 0.05, log-rank test). Statistical analysis revealed no correlation between p53 expression and patient's age, sex, immunotyping and initial peripheral blast cell count. PMID- 7872715 TI - Progesterone and estradiol stimulate release of epidermal growth factor/transforming growth factor alpha by ovarian tumours in vitro. AB - Previous studies have demonstrated locally increased steroid production and release of EGF/TGF-alpha in ovarian carcinomas. The influence of added steroid hormones on EGF-like activity in ovarian tumours in vitro was investigated. Using radioreceptor assay, EGF-like activity was measured in media from incubations of postmenopausal ovaries, benign and malignant epithelial ovarian tumours from 27 patients. The 3-hour incubations were performed with and without addition of progesterone, testosterone or estradiol. Addition of progesterone and estradiol significantly increased the release of EGF/TGF-a from benign tumour tissue but did not stimulate release from control ovaries. A stimulating effect was also noted for malignant tumour tissue but the increase was not significant. Addition of EGF or IGF-1 did not affect the release of steroid hormones from ovarian tumours. A positive correlation between progesterone and EGF-like activity was found in incubation media of peritoneal fluid cells from cancer patients. PMID- 7872716 TI - DNA synthesis inhibition and transmembrane permeation into tumor cells by various dialkyl phthalates upon hyperthermia. AB - Diisobutyl-, dibutyl-, and dioctyl phthalates, at a concentration of 50 microM, markedly inhibited the incorporation of [3H]thymidine into DNA in tumor cells and also cell proliferation. The inhibitions were synergistically enhanced by hyperthermia at 42 degrees C for 1 h. In contrast, dimethyl-, and diethyl phthalates induced almost no inhibition. The effective phthalates were detected in the cells by gas-liquid chromatography, whereas the non-effective drugs were not or were little detected, suggesting involvement of permeability through cell membrane in cytotoxic effects. Combination of the cytotoxic phthalic acid esters and hyperthermia is suggested to be an advantageous treatment for cancer. PMID- 7872718 TI - Effects on platelet function by human interferon-beta in carcinoma patients. AB - The effects of a therapeutic course of human interferon-beta (Hu IFN-beta) on platelet function were evaluated in 10 patients with neoplastic disorders. Each patient received, by intramuscular route, 6 x 10(6) IU of Hu IFN-beta every other day for 2 weeks. Platelet count, packed platelet volume, platelet size and in vitro aggregation tests were evaluated before IFN treatment and weekly during the treatment. An overall increase of in vitro platelet aggregation was present in all patients after the first week, and persisted after the second week of treatment. This effect was most pronounced when ADP and collagen were used as aggregation inducers. No significant differences were observed in IFN-gamma, IL 6, IL-1 beta and GM-CSF serum levels before and after IFN-beta treatment; nevertheless a parallel rise in IL-1 beta and/or GM-CSF and platelet count was noticed. The results obtained indicate that the effects of IFN-beta on platelet function are most likely due to a direct influence on bone marrow. PMID- 7872717 TI - Breast cancer response to adjuvant chemotherapy in correlation with erbB2 and p53 expression. AB - The expression of the erbB2 and p53 proteins was examined by immunohistochemistry in a series of 81 cases of primary breast carcinomas treated with an adjuvant chemotherapy with a median follow-up of 5 years. Expression of erbB2 was present in 19 cases (23%), 50% of them with more than 70% of positive tumoral cells. Expression of p53 was present in 32 cases (39%), 50% of them with more than 30% of positive tumoral cells; coexpression of erbB2 and p53 was observed in 11 cases (13.5%). Disease-free and overall survival of the patients were correlated with the number of positive lymph nodes (p = 0.08, p = 0.015). No significant trend was observed in response to adjuvant chemotherapy in correlation with erbB2 or p53 expression or both, whatever the level of expression. PMID- 7872719 TI - P53 mutations and loss of heterozygosity on chromosomes 8p, 16q, 17p, and 18q are confined to advanced prostate cancer. AB - We analysed 39 prostatic carcinomas for loss of heterozygosity on chromosomal arms 8p, 10q, 16q, 17p and 18q and for mutations in the p53 anti-oncogene. Loss of heterozygosity (LOH) on 8p was detected in one out of 5 informative tumors, LOH on 16q in 3 out of 21 tumors, LOH on 17p in 2 out of 18 tumors, and LOH on 18q in 2 out of 17 tumors. No deletions were observed on 10q in 14 informative tumors. p53 alterations occurred in 3 out of 38 examined tumors, comprising two point mutations and a small deletion. Chromosomal deletions and p53 mutations were confined to locally invasive prostatic carcinomas, suggesting that they are associated with the progression of some prostate cancers rather than with tumor initiation. PMID- 7872720 TI - Bone marrow metastases detection in small cell lung cancer. A review. AB - Small cell lung cancer is known to carry a high capacity to metastasize in various sites including bone marrow. We here review the respective sensitivities of classical cyto-histological methods and of more recently described techniques such as cell cultures, immunostaining with monoclonal antibodies and magnetic resonance imaging. These new and somehow less aggressive methods allow the detection of malignant cells in 50% or more of patients with small cell lung cancer. However, their potential usefulness in the staging of such patients as well as their therapeutic and clinical implications remain undetermined. Their possible clinical value needs to be evaluated in future trials. PMID- 7872721 TI - Effective conditioning regimen for premenopausal patients with advanced breast cancer. AB - The aim of the study was to define an effective regimen as induction treatment in chemotherapy naive patients with advanced breast cancer as preparation for ablative chemotherapy. PATIENTS AND METHODS: Patients with locally advanced or metastatic breast cancer (AJCC stage IIIB or IV) received 5-fluorouracil, methotrexate with leucovorin rescue and prednisone, alternating with doxorubicin and vincristine for six cycles. Results One hundred and eleven patients were eligible. All patients were evaluable for toxicity and seventy were evaluable for response. Thirty patients achieved a complete remission (43%) and 24 a partial remission (34%). Hematological toxicity was acceptable, as in 7% of 602 treatment cycles patients were admitted for neutropenic fever. Patients with liver metastases had a higher incidence of leucopenic fever, 32% compared to 15% for all patients, and a 25% incidence of cerebellar neuropathy compared to 9% for all patients. Mucositis more severe than WHO grade I occurred in 8% of cycles. Nausea and vomiting were not severe and cardiac or renal toxicity did not occur. Thromboembolic events occurred in 7% of the patients. CONCLUSIONS: This induction regimen carries a 43% complete and 77% overall remission rate, which is high compared to other conventional and even escalated regimens. The toxicity profile is acceptable except for the higher incidence of leucopenic fever and the reversible 5-FU cerebellar syndrome in patients with liver metastases. PMID- 7872722 TI - Transforming growth factor alpha, beta 1 and beta 2 in breast cyst fluid. AB - Women who have palpable breast cysts lined by apocrine metaplastic epithelium (intracystic Na/K < 3) may have a higher risk of breast cancer than those who have breast cysts lined by flattened epithelium (intracystic Na/K > 3). Transforming growth factor-alpha (TGF-alpha) exerts a proliferative effect on many cell types and may play a role in mammary carcinogenesis. Transforming growth factor-beta (TGF-beta) stimulates the proliferation of mesenchymal cells but inhibits mammary epithelial cell proliferation and may exert a protective effect against breast cancer development. The aim of this study was to measure the distribution of TGF-alpha, TGF-beta 1 and TGF beta 2 in the two sub-groups of breast cysts. TGF-alpha was undetectable in all but 2 of the 46 samples of breast cyst fluid tested. TGF-beta 1 ranged from undetectable up to 25.4 ng/ml (n = 46) while the intracystic concentrations of TGF-beta 2 were generally higher, ranging from 0.30 ng/ml to 125 ng/ml (n = 42). There was no significant difference between the distribution of TGF-beta 1 levels in the 2 cyst groups, but TGF-beta 2 levels were significantly higher (P < 0.001) in the high electrolyte ratio group (Na/K > 3). A negative correlation was found between TGF-beta 1 and TGF beta 2 levels in the high electrolyte ratio group (rs = 0.605, p = 0.006, n = 19). TGF-alpha is unlikely to play an important role in breast cancer development in women with palpable breast cysts. The significantly higher concentrations of TGF-beta 2 in the high electrolyte ratio group may explain, in part, the lower risk of breast cancer in this group of women. PMID- 7872723 TI - Characterization of p53 gene mutations in colorectal carcinomas from an Asian population. AB - A series of colorectal carcinomas from an Asian population in Singapore were analyzed for mutations in the tumor suppressor gene p53. Based on single-strand conformation polymorphism (PCR-SSCP) analysis and direct DNA sequencing, 15 of 38 tumors (39%) were found to contain mutations in exons 5-8 of the p53 gene. The point mutations were predominantly base transitions. Among the 10 transitions, 5 were at CpG dinucleotide sites. One-third (5/15) of the mutations were found at previously identified hotspot codons 175, 248 and 282. In one case, an insertion of a 6-base pair sequence was found. p53 mutations did not correlate with tumor histological grade, Dukes' stage, or metastases. However, tumors at the distal site showed a higher proportion of mutations than the proximal site. Further, no mutation was found in the normal mucosa adjacent to tumor site, suggesting that no germ-line mutations were present. The results were compared with those from other studies and are discussed in connection to possible etiological factors that are specific to the local population. PMID- 7872724 TI - Tissue polypeptide specific antigen in hepatitis B carriers. AB - Forty-three normal and thirty-five healthy Chinese hepatitis B carriers were included in our study for comparison with each other. The serum levels of tissue polypeptide specific antigen were measured with a method of immunoradiometric assay (IRMA). The results revealed that the mean +/- SD TPS levels in the 43 normal Chinese and 35 carriers are 85.0 +/- 16.0 and 131.9 +/- 20.1 U/L respectively. There is a significant statistical difference for the TPS level between the two groups. In conclusion, we suggest that the existence of hepatitis B surface antigen is an important factor affecting the serum level of TPS. PMID- 7872725 TI - Prognostic significance of preoperative serum CA 19.9 assay in patients with colorectal carcinoma. AB - The prognostic information provided by preoperative serum CEA and CA 19.9 antigen assay on the postoperative outcome of 150 patients with colorectal cancer was analysed. The influence of both markers was studied by Cox's proportional-hazard regression analysis. In the univariate analysis, patients whose initial CA 19.9 level was higher than 37 U/ml had a 4.32-fold greater risk of death due to the cancer (95% CI: 1.72-10.84) (p < 0.001) than patients with lower values. The 36 month survival rate posttreatment was lower for patients with CA 19.9 serum levels over 37 U/ml (61% versus 90%) (p < 0.001). Patients whose initial CEA level was higher than 5 ng/ml had a 2.9-fold greater risk of death (95% CI: 1.05 7.99) (p = 0.04) than patients with lower values. The 36-month survival rate posttreatment was lower for patients with CEA serum levels over 5 ng/ml (84% versus 76%) (p = 0.04). After adjustment for Dukes' stage, CEA, CA 19.9, tumor site, sex and age, only Dukes' stage and CA 19.9 continued to provide independent predictive information on survival. The risk of death increases by 1.008 for every 10 U/ml rise in the level of the marker (95% CI: 1.002-1.014) (p = 0.009). With respect to analysis of disease-free survival, only Dukes' stage provided independent predictive value. CA 19.9 is an independent prognostic factor of survival in colorectal cancer. The authors suggest including CA 19.9 in a future multifactorial analysis of survival. PMID- 7872726 TI - Spontaneous endometrial hyperplasia. A 5 year follow-up of 82 patients after high dose gestagen treatment. AB - Endometrial hyperplasia was proposed as a predecessor to endometrial carcinoma already at the end of the 19th century. However, there have been different opinions regarding this view. The treatment also varies, but generally cyclic progesterone at a dose of 10 mg a day is used. In order to investigate whether endometrial hyperplasia is a premalignant state and also whether a high-dose gestagen treatment would cure a high proportion of these patients, a prospective randomised study was started in 1982. We now present the 5 year follow-up consisting of 82 patients treated with high-dose gestagen. In this study 19 out of 82 patients had hysterectomies (2 due to hyperplasia and 11 due to bleeding), almost the same frequency as in a previous report with patients followed-up with abrasio only, but now mainly due to bleeding problems. In summary, no carcinoma developed and the hyperplasia was cured with 500 mg MPA i.m. twice weekly for three months. However, the bleeding problems, though almost always only spotting, remained, leading to a frequency of hysterectomy that was still too high. We find latter clinical problem an enigma. Further studies are therefore in progress in our group which try to identify other treatment modalities for those patients with bleeding problems or who redeveloped hyperplasia after abrasio, in order to avoid hysterectomies. PMID- 7872727 TI - Clinical significance of first line treatment in recurrent breast cancer. AB - From 1962 to 1992, 279 patients with recurrent breast cancer were treated. Of these, the cases with resected lesions, imperfectly evaluated cases and cases where information was lacking were excluded, and 185 recurrent breast cancers were evaluable at the first line or subsequent treatment. Sixty-seven (36.2%) out of 185 cases responded to first line treatment, while the remaining 118 cases did not respond. In the 67 responder cases at the first line treatments, 16 (23.9%) responded to second line or third line, however, in the 118 nonresponder cases, only 13 (11.0%) responded to next or subsequent treatment. The incidence of responder in the second line or third line treatment was significantly higher in the first line responder group than in the first line nonresponder group. Furthermore, overall survival of first line responders was significantly better than that of first line nonresponders. There was no significant difference in the survival after recurrence between responders and nonresponders in the first line chemotherapy, chemoendocrine treatment or radiotherapy, however, a significant difference was seen between the two groups in the first line endocrine treatment. These results suggest that first line treatment may select the treatment sensitive (especially, truly hormone-dependent) recurrent breast cancers which show a better prognosis. PMID- 7872728 TI - Prognostic significance of transforming growth factor alpha TGF-alpha) in human lung carcinoma: an immunohistochemical study. AB - Despite emerging data relating oncogene expression, growth factors and/or their receptors to the etiology of lung cancer, standard clinicopathological evaluation is still used for the diagnostic and prognostic purposes. Recent studies have shown that expression of some oncogenes and growth factors/receptors may be useful as markers in routine diagnostic and prognostic processes. For example, EGF/erb-B family of peptides may play a role in lung carcinogenesis. Similarly, expression of TGF-alpha mRNA and peptide has been shown to occur in various human lung carcinomas in vivo and in vitro. However, results concerning the role of TGF alpha in lung carcinoma are conflicting and therefore its clinical value still remains obscure. To better evaluate the potential value of TGF-alpha in clinical application we have investigated the relationship between TGF-alpha expression in 51 lung carcinomas and 26 different clinical and clinicopathological parameters. The only significant correlation noted was between TGF-alpha and venous blood erythrocytes and eosinophils. This study suggests a relationship between metastasis and aggressive behavior of lung cancer. This data shows that TGF-alpha expression can not serve as an independent tumor marker for lung cancer. PMID- 7872729 TI - Diagnosis and classification of psychopathology: challenges to the current system and future directions. PMID- 7872730 TI - Emotion: clues from the brain. PMID- 7872731 TI - Adolescent development: pathways and processes of risk and resilience. PMID- 7872732 TI - Aging and speed of behavior: possible consequences for psychological functioning. AB - Over 100 years of observations have established that slowness of behavior is a characteristic of becoming old, although it is now recognized that health, use of medications, and physical activity may modify the extent of the slowing. Early research indicated that there is a limited contribution to slowing by peripheral sensory-motor factors. Substantial evidence has pointed to the central nervous system as the locus of the slowing. Recent investigators have expressed divided opinions about whether there is a pervasive general slowing of behavior by the central nervous system or whether there are specific localized mechanisms. This is not unlike early disputed views of the brain as having localized or global behavioral functions: Both principles appear to be simultaneously true. Sufficient research has been conducted to indicate that there are specific factors as well as a general process associated with the slowing of behavior with advancing age. Whether such slowing is a primary or secondary cause of age differences in cognitive processes is a significant scientific issue. A marked broadening of research on aging has been accompanied by an interest in identifying both the neurophysiological correlates of slowing as well as its role in specific cognitive processes. Yet another aspect of the changing research picture is the trend to move beyond the mere use of chronological age as the sole basis for comparing performance differences. Measurement of more independent variables is suggested as part of clusters or causal complexes that will indicate sources of the changes in speed and other aspects of behavior. These causal complexes include biological indicators such as disease, physiological capacity for work, and length of life, as well as causal complexes of social factors involving such variables as education, occupation, and ethnicity. There has been considerable discussion of markers of aging. In this approach, factors found to be closely associated with advancing age are used as measures of the effectiveness of attempts to modify the course of aging, e.g. by diet, exercise, new learning, and drugs. Along with other biomarkers of aging, speed of behavior may prove to be a criterion for assessing the impact of interventions on the rate and processes of aging. As a marker of aging, speed needs further exploration that will compare the slowness observed in different subgroups of adults with a wide range of outcomes in their productivity, capacity for adaptation to life's demands, and health. The present status of information about slowness of behavior with advancing age indicates that it is one of the most reliable features of human life.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7872733 TI - Psychological characteristics of maltreated children: putative risk factors and consequences. AB - Although there is considerable evidence that the maltreatment of children is widespread and that it can have significant adverse effects on the victims, specific abuse-outcome patterns are not obvious beyond the link between physical abuse and aggression, and the link between sexual abuse and poor sexual adjustment. Although concepts of invulnerability or child resilience are somewhat controversial (see Rutter 1983), some children from severely maltreating backgrounds do not evidence apparent adverse outcomes (e.g. Farber & Egeland 1987, Herrenkohl et al 1991). It is unknown whether the more favorable outcomes are the result of child resilience or the influence of environmental buffers. More research clearly is needed to fully understand the behavioral risks and consequences of maltreatment. PMID- 7872734 TI - Data analysis: continuing issues in the everyday analysis of psychological data. PMID- 7872735 TI - Speech perception: from signal to word. PMID- 7872736 TI - Clinical assessment of memory disorders in amnesia and dementia. PMID- 7872737 TI - Genes and human behavior. PMID- 7872738 TI - Personality development in social context. PMID- 7872739 TI - Language comprehension: sentence and discourse processing. PMID- 7872740 TI - Proposed molecular and cellular mechanism for aminoglycoside ototoxicity. PMID- 7872741 TI - Effectiveness of various antimicrobial agents against Mycobacterium avium complex in the beige mouse model. AB - The results of five chemotherapeutic experiments in beige mice infected with organisms of the Mycobacterium avium complex are presented. After monotherapy with various antimicrobial agents for 4 weeks, only clarithromycin, amikacin, and ethambutol displayed definite bactericidal effects; sparfloxacin and clofazimine showed modest bacteriostatic effects; and rifampin and rifabutin were totally inactive against the isolate tested. After treatment for 4 weeks, the large quantities of clofazimine that had accumulated in the organs of mice seriously interfered with the enumeration of the CFU and assessment of the efficacy of the treatment. The in vitro synergistic effects of drug combinations against M. avium complex were not confirmed in beige mice. In combination with clarithromycin, amikacin could prevent the selection of clarithromycin-resistant mutants, whereas minocycline could not. PMID- 7872742 TI - Antimicrobial susceptibilities of Neisseria gonorrhoeae strains isolated in Surabaya, Indonesia. AB - Until recently, the only common strains of antimicrobial agent-resistant Neisseria gonorrhoeae detected in Indonesia were penicillinase-producing N. gonorrhoeae (PPNG) strains. Despite the spread of resistance to other antimicrobial agents among N. gonorrhoeae in Southeast Asia, surveillance for such resistance in Indonesia has been limited. We evaluated the in vitro susceptibilities of 86 N. gonorrhoeae isolates from female sex workers in Surabaya, Indonesia, to 13 antimicrobial agents. Of the 86 isolates, 89% were resistant to penicillin (MIC, > or = 2.0 micrograms/ml), 98% were resistant to tetracycline (MIC, > or = 2.0 micrograms/ml), 18.1% were resistant to spectinomycin (MIC, > or = 128.0 micrograms/ml), and 97.7% showed decreased susceptibility to thiamphenicol (MIC, 1 to 2 micrograms/ml). Thus, thiamphenicol and spectinomycin may be approaching the end of their usefulness as the drugs of choice for the treatment of gonococcal infections in Surabaya. While the susceptibilities of N. gonorrhoeae to cephalosporins (ceftriaxone, cefixime, and cefoxitin) and fluoroquinolones (ciprofloxacin and ofloxacin) are universal, these drugs have not been used because they are more expensive in Indonesia than thiamphenicol. We conclude that Surabaya had the highest reported rate of penicillin and tetracycline resistance among the Southeast Asian countries and that cephalosporins or fluoroquinolones should be reasonable alternatives for the treatment of gonorrhea in this locale. PMID- 7872743 TI - Phytosterols are present in Pneumocystis carinii. AB - Although originally classified as a protozoan, Pneumocystis carinii is now considered to have fungal characteristics. Drugs typically used for the treatment of fungal infections target ergosterol. Because P. carinii is an important pathogen in AIDS and other immunocompromised patients, knowledge of the sterol content of this organism may be useful as a basis for developing new treatment strategies or for improving diagnosis. P. carinii organisms were harvested from infected rat lungs and were purified by filtration. Control preparations from uninfected animals were identically prepared. Lipids were extracted from the organisms and control preparations and were separated into neutral lipid, glycolipid, and phospholipid fractions by silicic acid chromatography. The neutral lipid fraction was further treated by alkaline hydrolysis and was analyzed by reversed-phase high-pressure liquid chromatography (HPLC), gas chromatography (GC), and GC-mass spectrometry (GC-MS). As shown by HPLC, the neutral lipid fraction from infected rats contained a minimum of six peaks, while in control preparations a single peak with a retention time identical to that of cholesterol was observed. The predominant sterol in these preparations was positively identified by GC-MS as cholesterol and constituted 80 to 90% of the total. The remaining peaks had relative retention times similar to those of phytosterols by both HPLC and GC, and the similarity of these sterols to those derived from plants and fungi was confirmed by MS. Ergosterol, however, was not present. These results provide further evidence for a close phylogenetic relationship between P. carinii and fungi and suggest that these sterols could be used as targets for drug development and for improving diagnosis. PMID- 7872744 TI - Comparative efficacies of amphotericin B, triazoles, and combination of both as experimental therapy for murine trichosporonosis. AB - We assessed the activities of amphotericin B deoxycholate, liposomal amphotericin B, fluconazole, and SCH 39304 against 10 strains of Trichosporon beigelii in mice with hematogenous infections. Cyclophosphamide-immunosuppressed CF1 male mice were challenged intravenously with a lethal inoculum of T. beigelii (5 x 10(6) conidia per mouse) and were assigned to different treatment groups or were left untreated. Amphotericin B deoxycholate (1 mg/kg of body weight and liposomal amphotericin B (1, 5, and 10 mg/kg) were given parenterally once daily. Escalating doses (5, 10, and 20 mg/kg/day) of fluconazole and SCH 39304 were tested. We also compared the activity of amphotericin B deoxycholate plus fluconazole (1 and 10 mg/kg/day, respectively) with that of each agent alone. Fluconazole significantly prolonged the survival of mice infected with each of the 10 strains tested. Amphotericin B deoxycholate achieved various responses, improving the outcomes in mice infected with seven of the strains. Liposomal amphotericin B was not more effective than amphotericin B deoxycholate against the two strains tested. Both fluconazole and SCH 39304 reduced the kidney fungal counts in a dose-dependent pattern, with SCH 39304 being more active than fluconazole against one of the two strains tested. The activity of the combination of amphotericin B deoxycholate plus fluconazole appeared to be superior to that of either agent alone, especially in reducing the kidney fungal burden. Fluconazole is more active than amphotericin B deoxycholate against experimental murine trichosporonosis. PMID- 7872745 TI - Ornithine decarboxylase in Pneumocystis carinii and implications for therapy. AB - Pneumocystis carinii pneumonia (PCP) can be treated with eflornithine (difluoromethylornithine, DFMO, Ornidyl), a competitive irreversible inhibitor of ornithine decarboxylase (ODC), a key enzyme for polyamine biosynthesis. Because ODC has been reported to be absent from P. carinii, it has been assumed that eflornithine affects P. carinii only indirectly, by affecting host polyamine biosynthesis. If this is true, then improvements in the selectivity of antipolyamine therapy for PCP would be limited. Since the presence of ODC in P. carinii is an important issue, a new search for this enzyme was made. Not only were initial assays negative, but P. carinii extract reduced the background catalytic action of pyridoxal-5'-phosphate, the coenzyme required by the enzyme. This suggested the presence of an inhibitor, which was further supported by the observation that a P. carinii extract could suppress a source of known ODC activity. The inhibitory activity could be removed by a desalting column or by dialysis, allowing detection of P. carinii ODC. Indirect evidence indicates that the inhibition is only apparent and is caused by unlabeled ornithine in the extract of P. carinii which interferes with the radiolabel-based assay system. P. carinii and host ODCs respond differently to changes in pH. P. carinii ODC is much less susceptible to inhibition by eflornithine than host ODC. The presence of ODC in P. carinii suggests that P. carinii ODC is the target of eflornithine and that P. carinii ODC may have sufficiently specific properties that inhibitors with improved selectivity against P. carinii ODC could be identified. PMID- 7872746 TI - In vitro activity of a new antifungal triazole, D0870, against Candida albicans isolates from oral cavities of patients infected with human immunodeficiency virus. AB - We investigated the in vitro activity of a new antifungal triazole, D0870, against 100 Candida albicans isolates from the oral cavities of patients infected with human immunodeficiency virus by using a broth macrodilution method following the recommendations provided by the National Committee for Clinical Laboratory Standards (document M27-P). All of the isolates were chosen from C. albicans isolates already tested for fluconazole susceptibility by the procedure of the National Committee for Clinical Laboratory Standards. Fifty isolates were considered fluconazole susceptible (MICs, < or = 4 micrograms/ml), and 50 isolates were considered fluconazole resistant (MICs, > or = 8 micrograms/ml). The in vitro data demonstrated that D0870 had good activity against isolates tested; for 90% of all strains of C. albicans, MICs were 0.5 micrograms/ml. However, the D0870 MICs for the fluconazole-susceptible isolates were lower than those for the fluconazole-resistant isolates; MICs for 50 and 90% of the isolates tested were < or = 0.0078 and 0.06 micrograms/ml, respectively, for fluconazole susceptible isolates and 0.25 and 2 micrograms/ml, respectively, for fluconazole resistant isolates (P < 0.001). Our data suggest that this new triazole could represent a valid alternative in the treatment of oral candidiasis in human immunodeficiency virus-infected patients. PMID- 7872747 TI - A bone marrow-derived murine macrophage model for evaluating efficacy of antimycobacterial drugs under relevant physiological conditions. AB - Even though the macrophage is the host cell for the intracellular bacterial parasite Mycobacterium avium, macrophages have undergone only limited evaluation as models for determining the capacities of antimycobacterial drugs to inhibit the growth of M. avium within this relevant intracellular environment. In the present study, we demonstrated that a panel of M. avium isolates could actively infect homogeneous monolayers of murine bone marrow-derived macrophages. A number of established and experimental antimycobacterial drugs were then added to these cultures at a range of concentrations, and their effects on the numbers of surviving bacilli were determined 8 days later. By plotting such numbers versus drug concentrations it was then possible to clearly distinguish between compounds with bactericidal activity (such as rifabutin and PD 125354) and those with bacteriostatic effects (such as clarithromycin), even though several of these compounds had very similar MICs. In addition, an estimate of the potential therapeutic efficiency of each drug could be made by determining the concentration needed to destroy an arbitrary percentage of the inoculum (in this case, the bactericidal concentration destroying 99% of the inoculum). Such values were considerably in excess of the MICs and may more realistically reflect the concentrations in serum required to effectively reduce the bacterial burden in vivo. PMID- 7872748 TI - Bacteria: a major pathogenic factor for anastomotic insufficiency. AB - The aim of this study was to determine the influence of bacteria on the development of anastomotic insufficiency following gastrectomy in the rat. Fifty seven male Wistar rats were randomly assigned to three groups and subjected to gastrectomy. Group I (n = 20) was orally inoculated with 10(9) Pseudomonas aeroginosa organisms on postoperative day 1. Group II (n = 20) served as the control group. Group III (n = 17) was decontaminated with 320 mg of tobramycin, 400 mg of polymyxin B, and 500 mg of vancomycin per liter of fluid administered from preoperative day 7 to postoperative day 10. Swabs from the oropharynx and rectum were cultured and analyzed daily for gram-positive and gram-negative bacteria. Surviving animals were sacrificed on postoperative day 10. All animals were autopsied immediately following death. Anastomotic insufficiency was defined as a histologically proven transmural defect at the suture line. Along with an effective reduction of pathogenic bacteria colonizing the oropharynx, the rate of anastomotic insufficiency could be reduced significantly, to 6% in decontaminated animals compared with 80% in controls (P < 0.001 by Fisher's exact test). Inoculation of group I animals with P. aeruginosa led to an increase of anastomotic insufficiency up to 95% and a significant increase in mortality (P < 0.05). We conclude that bacteria play a major role in the pathogenesis of anastomotic insufficiency following gastrectomy in the rat. PMID- 7872749 TI - Altered production of penicillin-binding protein 2a can affect phenotypic expression of methicillin resistance in Staphylococcus aureus. AB - Altered production of penicillin-binding protein 2a (PBP 2a) may affect the phenotypic expression of resistance in methicillin-resistant Staphylococcus aureus (MRSA). COL, an MRSA strain that constitutively produces PBP 2a, was transformed with a recombinant plasmid containing the two beta-lactamase regulatory genes, blaI and blaR1, with either the beta-lactamase gene, blaZ, or a truncated blaZ. Both of the transformed MRSA strains now produced an inducible PBP 2a, and the MICs of nafcillin, methicillin, and imipenem for these strains were similar to those for the parental strain. A mutation in blaR1 that resulted in the complete repression of PBP 2a production altered the phenotypic expression of methicillin resistance in that strain, as evidenced by efficiency-of-plating experiments. Rather than being homogeneously resistant like COL, the blaR1 mutant strain now appeared to have a small resistant subpopulation. Gene products that regulate PBP 2a production may contribute to the organism's expression of methicillin resistance, but additional chromosomally located factors are required. PMID- 7872750 TI - Guanylhydrazones in therapy of Pneumocystis carinii pneumonia in immunosuppressed rats. AB - Guanylhydrazones are cationic heteroaromatic drugs similar to the diamidines which are effective in the treatment of African trypanosomiasis and pneumocystosis. On the basis of their antitrypanosomal activity, different guanylhydrazones were selected for evaluation in a rat model of Pneumocystis carinii pneumonia. The most active compounds were the 2-(4'-formylphenyl)-1 methylimidazo-[1,2-a] pyridinium guanylhydrazones which, at a dose of 2 mg/kg/day, were about as effective as trimethoprim-sulfamethoxazole at a dose of 50 mg of trimethoprim per kg/day plus 250 mg of sulfamethoxazole per kg/day. The anti-P. carinii activity of these guanylhydrazone derivatives was found with parenteral but not with oral administration. The 1,3-arylene diketone bis(guanylhydrazones) were generally ineffective, although a triacetyl derivative showed some anti-P. carinii activity. Nitroimidazole guanylhydrazone derivatives were also ineffective. Attempts to improve the therapeutic efficacy of the different guanylhydrazones were limited by problems of toxicity. We conclude that some guanylhydrazone derivatives are potent anti-P. carinii drugs and that further studies should be pursued to develop safer compounds and investigate structure-activity relationships. PMID- 7872751 TI - Ultrasonic enhancement of antibiotic action on gram-negative bacteria. AB - The effect of gentamicin upon planktonic cultures of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, and Staphylococcus aureus was measured with and without application of 67-kHz ultrasonic stimulation. The ultrasound was applied at levels that had no inhibitory or bactericidal activity against the bacteria. Measurements of the MIC and bactericidal activity of gentamicin against planktonic cultures of P. aeruginosa and E. coli demonstrated that simultaneous application of 67-kHz ultrasound enhanced the effectiveness of the antibiotic. A synergistic effect was observed and bacterial viability was reduced several orders of magnitude when gentamicin concentrations and ultrasonic levels which by themselves did not reduce viability were combined. As the age of the culture increased, the bacteria became more resistant to the effect of the antibiotic alone. Application of ultrasound appeared to reverse this resistance. The ultrasonic treatment-enhanced activity was evident with cultures of P. aeruginosa and E. coli but was not observed with cultures of gram-positive S. epidermidis and S. aureus. These results may have application in the treatment of bacterial biofilm infections on implant devices, which infections are usually more resistant to antibiotic therapy. PMID- 7872752 TI - Postantibiotic effect of meropenem on members of the family Enterobacteriaceae determined by five methods. AB - The postantibiotic effect (PAE) of meropenem was determined for 11 strains, both clinical isolates and reference strains of members of the family Enterobacteriaceae. The study compares PAE results obtained by five methods used to monitor bacterial regrowth, including viable counting, alone and in combination with impedance; bioluminescence, alone and in combination with impedance; and a morphological technique. After exposure of the test organisms to meropenem (0.1 x to 100 x MIC) for 2 h, concentration-dependent differences in counts by bioluminescence and viable counts were observed, the latter always being lower. The differences varied with the test organism. For example, after exposure of Providentia stuartii NCTC 10318 to 0.1 x MIC, the counts were 5.5 x 10(5) and 2.0 x 10(5) whereas after exposure of Citrobacter freundii MR76 to 0.1 x MIC of meropenem the counts were 2.3 x 10(6) and 6.8 x 10(3) by bioluminescence and viable counting, respectively. The discrepancies were probably due to the relative inability of the viable counting procedure to detect fragile aberrant morphologies and resulted in differences in the calculated PAE values. With methods which do not detect fragile morphologies, the PAE may be underestimated. A general trend was observed for the order of magnitude of the PAEs by the following methods (in order of decreasing magnitude of PAE): (i) morphological technique, (ii) bioluminescence technique alone, (iii) bioluminescence in combination with impedance, (iv) viable counting in combination with impedance, and (v) viable counting alone. It is our opinion that of the methods examined in this study, bioluminescence in combination with impedance best reflects the true values for PAEs, and these results were examined more closely. PMID- 7872753 TI - Reassessment of the number of auxiliary genes essential for expression of high level methicillin resistance in Staphylococcus aureus. AB - A new transposon library constructed in the background of the highly and homogeneously methicillin-resistant Staphylococcus aureus strain COL yielded 70 independent insertional mutants with reduced levels of antibiotic resistance. Restriction analysis with HindIII, EcoRV, EcoRI, and PstI and then Southern hybridization with probes for the transposon and for the femA-femB gene demonstrated that 41 of the 70 Tn551 mutants carried distinct and novel, as yet undescribed insertion sites, all of which were outside of the mecA gene and were also outside the already-characterized auxiliary genes femA, femB, femC, and femD. All previously described Tn551 mutations of this type were in genes located either on SmaI fragment A or SmaI fragment I. In contrast, inserts of the new library were located in 7 of the 16 SmaI chromosomal fragments, fragments A, B, C, D, E, F, and I. In all of the mutants, expression of methicillin resistance became heterogeneous, and the MIC for the majority of cells was reduced (1.5 to 200 micrograms ml-1) from the homogeneous methicillin MIC (1,600 micrograms ml-1) of the parental cells. Although identification of the exact number of genes inactivated through the new set of transposon inserts will require cloning and sequencing, a rough estimate of this number from mapping data suggests a minimum of at least 10 to 12 new genetic determinants, all of which are needed together with femA, femB, femC, and femD for the optimal expression of methicillin resistance. PMID- 7872754 TI - Activity of WY-49605 compared with those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 anaerobic bacteria. AB - The National Committee for Clinical Laboratory Standards agar dilution method was used to compare the in vitro activity of WY-49605 (also called SUN/SY 5555 and ALP-201), a new broad-spectrum oral penem, to those of amoxicillin, amoxicillin clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 clinically isolated anaerobes. These anaerobic organisms included 90 strains from the Bacteroides fragilis group, 87 Prevotella and Porphyromonas strains, non-B. fragilis group Bacteroides strains, 56 fusobacteria, 55 peptostreptococci, 49 gram-positive non-spore-forming rods, and 47 clostridia. Overall, WY-49605 had an MIC range of 0.015 to 8.0 micrograms/ml, an MIC at which 50% of the isolates are inhibited (MIC50) of 0.25 microgram/ml, and an MIC at which 90% of the isolates are inhibited (MIC90) of 2.0 micrograms/ml. Good activity against all anaerobe groups was observed, except for Clostridium difficile and lactobacilli (MIC50s of 4.0 and 2.0 micrograms/ml, respectively, and MIC90s of 8.0 and 2.0 micrograms/ml, respectively). Imipenem had an MIC50 of 0.03 microgram/ml and an MIC90 of 0.25 microgram/ml. Ciprofloxacin was much less active (MIC50 of 2.0 micrograms/ml and MIC90 of 16.0 micrograms/ml). By comparison, all oral beta-lactams were less active than WY 49605, with susceptibilities as follows: amoxicillin MIC50 of 8.0 micrograms/ml and MIC90 of > 256.0 micrograms/ml), amoxicillin-clavulanate MIC50 of 1.0 microgram/ml and MIC90 of 8.0 micrograms/ml, cefaclor MIC50 of 8.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml, cefpodoxime MIC50 of 4.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml, and cefuroxime MIC50 of 4.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml. Clindamycin was active against all groups except some members of the B. fragilis group, Fusobacterium varium, and some clostridia ( overall MIC50 of 0.5 micrograms/ml and overall MIC90 of 8.0 micrograms/ml). Metronidazole was active (MIC of less than or equal to 4.0 micrograms/ml) against all gram-negative anaerobic rods, but most gram-positive non-spore-forming rods, some peptostreptococci, and some clostridia were less susceptible. To date, WY 49605 is the most active oral beta-lactam against anaerobes: these results suggest clinical evaluation for clinical indications suitable for oral therapy. PMID- 7872755 TI - Effects of naftifine and terbinafine, two allylamine antifungal drugs, on selected functions of human polymorphonuclear leukocytes. AB - Many antimycotic agents negatively affect the natural immune response. Typically, these drugs impair polymorphonuclear leukocyte (PMN) production of superoxide anion, chemotaxis, or the killing of pathogens. Allylamines are a new class of antimycotic compounds with a new mechanism of antifungal action, i.e., inhibition of the fungal squalene epoxidase. The trial that we describe aimed to evaluate the effects of two allylamines, terbinafine and naftifine, on selected functions of PMNs, i.e., superoxide anion production, chemotaxis, and killing of Candida albicans blastospores. Terbinafine and naftifine on their own did not affect superoxide anion production when they were added to PMNs. When PMNs were preincubated with allylamines and were then stimulated by N-formyl-Met-Leu-Phe or phorbol 12-myristate 13-acetate, superoxide anion production was increased (priming effect). Since intracellular free calcium (Ca2+i) is involved in the control of superoxide anion production, we evaluated the effects of the allylamines on the Ca2+i concentration ([Ca2+]i). In the presence of terbinafine or naftifine, the [Ca2+]i increased in a dose-dependent manner; the source of Ca2+i was not extracellular since it was not affected by extracellular calcium chelation with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. In the presence of terbinafine or naftifine, chemotaxis of PMNs was not impaired. Terbinafine and naftifine slightly but significantly increased the killing of C. albicans blastospores (P < 0.05 at 10 and 100 microM). In conclusion, in contrast to imidazole-like drugs, the allylamine antimycotic compounds terbinafine and naftifine enhance selected functions of PMNs. PMID- 7872756 TI - Single-dose fosfomycin trometamol versus 5-day cephalexin regimen for treatment of uncomplicated lower urinary tract infections in women. AB - A randomized study was conducted to assess the clinical and microbiological efficacies of a single 3-g dose of fosfomycin trometamol for the treatment of uncomplicated lower urinary tract infections in women compared with a 5-day regimen of cephalexin at 0.5 g four times daily. One hundred twelve women, all of whom had documented infections with bacteria sensitive to both antibiotics, were included. Fifty-eight women received fosfomycin trometamol, and 54 women received cephalexin. The two groups did not differ in age, severity, or duration of current urinary tract infection, menstrual status, sexual activity, or use of contraceptives. Ninety percent of pathogens in the fosfomycin trometamol group and 81% in the cephalexin group were Escherichia coli (the difference is not significant [NS]). A clinical evaluation at the 5-day follow-up showed that 91% of the women in each group were free of symptoms, while five women in each group were considered therapy failures and were treated by another antibiotic course. A microbiological evaluation at the 5-day follow-up showed a 91% eradication rate in the fosfomycin trometamol group and an 83% eradication rate in the cephalexin group (NS). At the 1-month follow-up, a clinical evaluation demonstrated prolonged resolution in 86 and 78%, respectively, of the participating women (NS). A microbiological evaluation at 1 month demonstrated prolonged eradication in 47 (81%) women treated with fosfomycin trometamol and in 37 (68%) women treated with cephalexin (NS). Three and six women, respectively, had relapsed. No adverse reactions were reported by the fosfomycin trometamol-treated women, while three women treated with cephalexin reported mild adverse reactions but completed the study period. Fosfomycin trometamol in a single 3-g dose is as effective as a 5-day regimen of cephalexin for the treatment of uncomplicated lower urinary tract infection in women. PMID- 7872757 TI - In vitro activity of the new fluoroquinolone CP-99,219. AB - The in vitro activity of the new fluoroquinolone CP-99,219 [7-(3 azabicyclo[3.1.0]hexyl)naphthyridone] was compared with those of four other quinolones against 541 gram-negative, 283 gram-positive, and 70 anaerobic bacterial isolates. CP-99,219 inhibited 90% of many isolates in the family Enterobacteriaceae at a concentration of < or = 0.25 micrograms/ml (range, < 0.008 to 1 microgram/ml), an activity comparable to those of tosufloxacin and sparfloxacin and two times greater than that of temafloxacin. Ninety percent of the Proteus vulgaris, Providencia rettgeri, Providencia stuartii, and Serratia marcescens isolates were inhibited by 0.5 to 2 micrograms of CP-99,219 per ml. CP 99,219 inhibited 90% of the Pseudomonas aeruginosa and Haemophilus influenzae isolates at 1 and 0.015 micrograms/ml, respectively. The compound inhibited methicillin-susceptible Staphylococcus aureus at 0.06 micrograms/ml, whereas a ciprofloxacin concentration of 1 microgram/ml was required to inhibit these organisms. CP-99,219 inhibited 90% of methicillin-resistant S. aureus isolates at a concentration of < or = 4 micrograms/ml, while ciprofloxacin and temafloxacin had MICs against these isolates of > 16 micrograms/ml. Streptococci were inhibited by < or = 0.25 micrograms/ml, an activity comparable to that of tosufloxacin. CP-99,219 was eight times more active than ciprofloxacin against Streptococcus pneumoniae. Bacteroides species were inhibited by CP-99,219 at a concentration of 2 micrograms/ml, whereas inhibition of these species required 4- and 16-microgram/ml concentrations of tosufloxacin and ciprofloxacin, respectively. The MBCs of CP-99,219 ranged from two to four times the MICs, and inoculum size had a minimal effect on MIC. CP-99,219 was active against P. aeruginosa at pH 5.5, with only a fourfold increase in MIC compared with values obtained at pH 7.5. The addition of up to 9 mM Mg(2+) increased the MIC range from 0.03 to 0.06 microgram/ml to 0.12 to 0.5 microgram/ml. In view of its excellent in vitro activity against both gram-positive and gram-negative bacteria, CP-99,219 merits further study to determine it's clinical pharmacologic properties and potential for therapeutic use. PMID- 7872758 TI - Comparison of inhibition of Escherichia coli topoisomerase IV by quinolones with DNA gyrase inhibition. AB - In order to examine the inhibitory activities of quinolones against topoisomerase IV, both subunits of this enzyme, ParC and ParE, were purified from Escherichia coli. The specific activity of topoisomerase IV decatenation was found to be more than five times greater than that of topoisomerase IV relaxation. Thus, the decatenation activity of topoisomerase IV seems the most relevant activity for use in studies of drug inhibition of this enzyme. Although topoisomerase IV was less sensitive to quinolones than DNA gyrase, the 50% inhibitory concentrations for decatenation were significantly lower than those for type I topoisomerases. Moreover, there was a positive correlation between the inhibitory activity against topoisomerase IV decatenation and that for DNA gyrase supercoiling. These results imply that topoisomerase IV could be a target for the quinolones in intact bacteria and that quinolones could inhibit not only supercoiling of DNA gyrase but also decatenation of topoisomerase IV when high concentrations of drug exist in bacterial cells. PMID- 7872759 TI - Susceptibilities of Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum to new glycylcyclines in comparison with those to older tetracyclines. AB - The glycylcyclines are new tetracycline derivatives that include the N,N dimethylglycylamido derivative of minocycline (DMG-MINO) and the N,N dimethylglycylamido derivative of 6-demethyl-6-deoxytetracycline (DMG-DMDOT). The susceptibilities of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum to DMG-MINO, DMG-DMDOT, tetracycline, doxycycline, and minocycline were determined by the agar dilution method. The glycylcyclines with MICs at which 50% of the isolates are inhibited of 0.25 to 0.5 micrograms/ml for M. pneumoniae were two- to fourfold more active than tetracycline and had the same activity as minocycline and doxycycline. Tetracycline-susceptible M. hominis strains were four- to eightfold more susceptible to the glycylcyclines (0.12 to 0.25 micrograms/ml) than to tetracycline. Strains of M. hominis known to be resistant to tetracycline, doxycycline, and minocycline because of the tet(M) determinant were as susceptible to the glycylcyclines as the tetracycline susceptible strains. For tetracycline-susceptible U. urealyticum strains, the glycylcyclines showed the same activity as tetracycline (MICs at which 50% of the isolates are inhibited of 1 to 2 micrograms/ml). Tetracycline-resistant strains of U. urealyticum were resistant to doxycycline and minocycline and showed variable susceptibility to the glycylcyclines (range, 0.5 to 32 micrograms/ml). In view of the increasing resistance of M. hominis and U. urealyticum strains to tetracyclines, the glycylcyclines have promise, pending assessment of their pharmacokinetic and safety profiles. PMID- 7872760 TI - Inhibition of antibacterial activity of himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus, by fatty acid sodium salts. AB - Himastatin, a cyclohexadepsipeptide antibiotic, had in vivo antitumor activity against localized P388 leukemia and B16 melanoma but had no distal site antitumor activity. An in vitro Bacillus subtilis well-agar diffusion assay was employed to test the hypothesis that himastatin was enzymatically inactivated. The activity of himastatin against B. subtilis was inhibited when himastatin was mixed with mouse liver S9 fraction and microsomes. However, subsequent investigations demonstrated that the markedly decreased antibacterial activity was not enzymatic in nature but was related to the presence of certain fatty acid salts. Saturated fatty acid sodium salts with a carbon chain number of 8 or more reduced the antimicrobial activity of himastatin 50 to 100 times. If antibiotics such as ampicillin, bacitracin, chloramphenicol, and tunicamycin were used in place of himastatin, no meaningful reduction in antibacterial activity occurred. However, the antibacterial activity of the membrane-active peptide antibiotic polymyxin B, but not that of polymyxin E (colistin), was reduced in a manner similar to that of himastatin. Importantly, the activity of himastatin against HCT-116 colon adenocarcinoma cells in soft agar was markedly reduced in the presence of sodium palmitate as the reference fatty acid salt. The data indicate that himastatin may be trapped in micelles in vitro. It may be speculated that the lack of distal site antitumor activity resulted from similar complex formation between himastatin and lipids in vivo. The results also suggest that the cancer cytotoxic and antimicrobial effects of himastatin may result from interactions with the cell membrane. PMID- 7872761 TI - Growth of Cryptococcus neoformans in presence of L-dopa decreases its susceptibility to amphotericin B. AB - Cryptococcus neoformans grown with L-dopa was melanized and was less susceptible to amphotericin B. The results suggest that in vivo and in vitro susceptibilities to amphotericin B may differ. PMID- 7872762 TI - In vitro antimycoplasmal activities of rufloxacin and its metabolite MF 922. AB - The in vitro activities of rufloxacin and its metabolite, MF 922, were compared with those of ofloxacin, ciprofloxacin, erythromycin, and minocycline against Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma fermentans, and Ureaplasma urealyticum. Rufloxacin, MF 922, and ciprofloxacin shared similar activities against all mycoplasmas tested. (MICs for 90% of isolates tested [MIC90s], 0.5 to 4 micrograms/ml. Ofloxacin had the lowest MIC90s for U. urealyticum, M. fermentans, and M. hominis (MIC90s, 0.25 to 1 micrograms/ml) and erythromycin had the lowest MIC90 for M. pneumoniae (MIC90, 0.004 micrograms/ml). PMID- 7872763 TI - In vitro killing activities of antibiotics at clinically achievable concentrations in cerebrospinal fluid against penicillin-resistant Streptococcus pneumoniae isolated from children with meningitis. AB - We evaluated the in vitro killing activities of ceftriaxone, imipenem, vancomycin, gentamicin, fosfomycin, and rifampin, alone and in combination, against 26 Streptococcus pneumoniae strains (penicillin G MICs, > 0.125 to 2 micrograms/ml) isolated from the cerebrospinal fluid of children with meningitis. The antibiotics were tested at clinically achievable concentrations in cerebrospinal fluid. After 5 h of incubation, imipenem was the most effective drug. None of the combinations had synergistic activity. Killing by beta-lactam antibiotics or vancomycin was enhanced by the addition of gentamicin, reduced by the addition of rifampin, and unaffected by the addition of fosfomycin. PMID- 7872764 TI - Efficacy of escalating doses of liposomal amphotericin B (AmBisome) against hematogenous Candida lusitaniae and Candida krusei infection in neutropenic mice. AB - Immunosuppressed CF1 mice were infected intravenously with two strains of Candida krusei and four strains of Candida lusitaniae (two of which were resistant to amphotericin B). Mice were treated with 1 or 2 mg of amphotericin B desoxycholate per kg of body weight per day or escalating doses of liposomal amphotericin B (8 to 30 mg/kg/day) or were left untreated. Higher doses of liposomal amphotericin B were as effective as standard dose of amphotericin B desoxycholate in prolonging survival but were significantly more effective in reducing the fungal burden in the kidneys of animals infected with both C. krusei strains and the C. lusitaniae strains that were susceptible to amphotericin B desoxycholate. This advantage of liposomal amphotericin B therapy could not be demonstrated in mice infected with the C. lusitaniae strains that were resistant to amphotericin B desoxycholate. PMID- 7872765 TI - In vivo efficacies of beta-lactam-beta-lactamase inhibitor combinations against a TEM-26-producing strain of Klebsiella pneumoniae. AB - We examined the efficacies of the beta-lactam-beta-lactamase inhibitor combinations ampicillin-sulbactam and piperacillin-tazobactam in the treatment of intra-abdominal abscesses caused by a TEM-26-producing strain of Klebsiella pneumoniae. At lower doses, both combinations reduced abscess colony counts by more than 3 log10 CFU/g from that of untreated controls, but treatment with these drugs was inferior to treatment with imipenem. Increasing the doses of the combinations resulted in a further decrease in abscess CFU to a level where both were similar to imipenem in efficacy. These results suggest that the beta-lactam beta-lactamase inhibitor combinations ampicillin-sulbactam and piperacillin tazobactam may be viable alternatives for the treatment of serious infections caused by susceptible extended-spectrum beta-lactamase-producing strains of K. pneumoniae. PMID- 7872766 TI - Effects of agars on determination of potency of polymyxin B sulfate by the agar plate diffusion method. AB - The effects of agars on the determination of the potency of polymyxin B sulfate by the agar plate diffusion method were investigated. The results showed that there were significant differences in the potency of polymyxin B sulfate between agars produced by different manufacturers. In order to investigate this phenomenon, two major components of polymyxin B sulfate, namely, the polymyxin B1 and B2 fractions, were isolated and purified by preparative high-pressure liquid chromatography, and the effects of agars on the potencies of these two components were individually examined. The results showed that there were significant differences in the relative potency of the B1 component versus that of the B2 component between the agar preparations produced by different manufacturers. On the basis of the relative potency of each of the components and the composition of the components, we developed a theoretical equation with which we could calculate the activity of polymyxin B sulfate on a certain agar. The values computed from the equation were consistent with those obtained from actual measurements. It was concluded that the effects of agars on the determination of polymyxin B sulfate activity will become evident only when the composition of the reference standard significantly differs from that of the samples. When the standard and samples have the same compositions, the sources of the agar preparation exert no effect on the determination of the potency by the agar plate diffusion method. PMID- 7872767 TI - Antimicrobial resistance of Shigella isolates causing traveler's diarrhea. AB - Shigella isolates were identified as a cause of traveler's diarrhea in 67 (10%) of 675 patients and were tested for resistance to seven antimicrobial agents in a comparative study with those causing nontraveler's diarrhea in Spain. Ampicillin and chloramphenicol resistance was more frequent in Shigella flexneri (60 and 46%, respectively) than in Shigella sonnei (32 and 18%, respectively) and in travel-related isolates (P < 0.05 and 0.04, respectively). Of S. sonnei isolates from patients with traveler's diarrhea, 73 and 54% showed tetracycline and trimethoprim-sulfamethoxazole resistance, respectively, compared with only 8% of isolates from patients without a history of travel to developing countries (P < 0.007 and P < 0.0002). Low-level resistance to cephalosporins was found, whereas quinolone-resistant strains were not detected among travel-related Shigella isolates. Thus, quinolones may be an effective alternative therapy for travel related shigellosis. PMID- 7872768 TI - Unilamellar liposomes modulate secretion of tumor necrosis factor by lipopolysaccharide-stimulated macrophages. AB - Liposomal encapsulation of antimicrobial agents has been used to improve drug delivery, particularly against intracellular pathogens. The effect of unilamellar liposomes on macrophage activation in response to Escherichia coli lipopolysaccharide was examined. Liposomes caused a dose- and time-dependent inhibition of tumor necrosis factor release by lipopolysaccharide-treated cells. The accumulation of tumor necrosis factor mRNA transcripts was unaffected, suggesting a posttranscriptional mechanism for this effect. However, induction of macrophage procoagulant activity was unaffected by liposomes, indicating a selective rather than a global inhibition. These data suggest that liposomes used for drug delivery may modulate the host response to infection. PMID- 7872769 TI - Activities of clarithromycin, ofloxacin, and clarithromycin plus ethambutol against Mycobacterium simiae in murine model of disseminated infection. AB - After 2 weeks of intravenous challenge with Mycobacterium simiae, ICR outbred mice were treated with clarithromycin, ofloxacin, or clarithromycin plus ethambutol for 4 weeks. All three therapy groups demonstrated a decrease in the level of infection in both the lungs and the spleen. There were no significant differences among the three treated groups in decreasing mycobacterial counts in the lungs; however, both ofloxacin and clarithromycin plus ethambutol were superior to clarithromycin alone in reducing the level of infection in the spleen. Results of the study suggest a potential role for these agents in the treatment of human M. simiae infection. PMID- 7872770 TI - Transient adaptation to oxidative stress in yeast. AB - Adaptive responses to the oxidative stress of hydrogen peroxide (H2O2) were studied in the yeast Saccharomyces cerevisciae strain RZ53. Our results show that the growth of naive cells is readily arrested by H2O2 challenge. In contrast, cells that have been preexposed to relatively low H2O2 priming treatments (i.e., cells that have first been pretreated with low H2O2 concentrations) are able to survive a subsequent challenge dose and continue to divide at normal rates. The most effective adaptation was observed with the following conditions: 5 x 10(6) cells/ml at pretreatment, pretreatment or priming peroxide addition of 0.4 mM H2O2, interval between pretreatment and challenge of 45 min, challenge peroxide concentration of 0.8 mM H2O2 for 2 h. Under these conditions cells that were challenged without pretreatment exhibited a 90% loss of plating efficiency. In contrast, peroxide-pretreated cells grew and divided at rates that were actually 15-30% faster than those of nonpretreated cells, and some 90-100% of such pretreated cells continued to divide at normal rates even following exposure to the H2O2 challenge concentration. The increased H2O2 resistance of pretreated cells was transient, being readily reversed during 60-90 min of growth in the absence of H2O2. Furthermore, cells that were allowed to deadapt over a 4-h period again exhibited a transient adaptive response when reexposed to H2O2 pretreatment. These results, plus the high survival rates (90-100%) of H2O2 pretreated and challenged cells, demonstrates that our results represent a true transient adaptation, rather than a selection for any preexisting peroxide resistant subpopulation. H2O2 adaptation required protein synthesis as evidenced by studies with the translational inhibitor, cycloheximide. At least 21 proteins exhibited increased expression following H2O2 adaptation, while the expression of some 8 other proteins was decreased. Adaptation is now widely reported in bacterial strains and has also been observed in some mammalian cell lines. We propose that the basis for such adaptive responses rests in increased expression of genes that encode protective enzymes and repair enzymes. PMID- 7872771 TI - Accumulation of a novel glycolipid and a betaine lipid in cells of Rhodobacter sphaeroides grown under phosphate limitation. AB - Cells of the photosynthetic bacterium Rhodobacter sphaeroides grown under phosphate-limiting conditions accumulated nonphosphorous glycolipids and lipids carrying head groups derived from amino acids. Concomitantly, the relative amount of phosphoglycerolipids decreased from 90 to 22 mol% of total polar lipids in the membranes. Two lipids, not detectable in cells grown under standard conditions, were synthesized during phosphate-limited growth. Fast atom bombardment mass spectroscopy, exact mass measurements, 1H NMR spectroscopy, sugar composition analysis, and methylation analysis of the predominant glycolipid led to the identification of the novel compound 1,2-di-O-acyl-3-O-[alpha-D-glucopyranosyl-(1 ->4)-O-beta-D-galactopyr anosyl]glycerol. The second lipid was identified as the betaine lipid 1,2-di-O-acyl-[4'-(N,N,N-trimethyl)-homoserine]glycerol by cochromatography employing an authentic standard from Chlamydomonas reinhardtii, fast atom bombardment mass spectroscopy, exact mass measurements, and 1H NMR spectroscopy. Prior to this observation, the occurrence of this lipid was thought to be restricted to lower plants and algae. Apparently, these newly synthesized nonphosphorous lipids, in addition to the sulfo- and the ornithine lipid also found in R. sphaeroides grown under optimal conditions, take over the role of phosphoglycerolipids in phosphate-deprived cells. PMID- 7872772 TI - Terminal marking of avian triosephosphate isomerases by deamidation and oxidation. AB - Triosephosphate isomerase (TPI) provides an excellent model for terminal marking and protein degradation. Mammalian TPI is terminally modified by deamidation at Asn71-Gly, resulting in unfolding, dissociation, and proteolysis. In contrast, chicken TPI, which contains a lysine at position 71, is terminally modified by the oxidation of Cys126. Thus, both deamidation and oxidation initiate degradation of TPI from different species. To explore the terminal marking in other avians, we have purified the turkey TPI to homogeneity and determined its characteristics. Although the molecular properties of the turkey and chicken TPI were very similar, their tolerances to temperature, oxidants, and alkaline pH were very different. For example, chicken TPI was inactivated 80% in either 10 mM oxidized glutathione or H2O2, whereas 120 mM GSSG had no effect on turkey TPI, and > 120 mM H2O2 was needed for 80% inactivation. Under alkaline conditions that cause rapid deamidation of the mammalian TPI, neither avian enzyme deamidated. Chicken TPI, however, aggregated. Aggregation was reversed by 2-mercaptoethanol. Under prolonged exposure to milder conditions the turkey enzyme was completely inactivated and deamidated at Asn15-Gly. Thus, there are marked differences in the susceptibility of these two avian enzymes to oxidation and deamidation, and their terminal marking mechanisms appear to be different. PMID- 7872773 TI - Ferrous ion strongly promotes the ring opening of the hydrolysis intermediates of the antioxidant cardioprotective agent dexrazoxane (ICRF-187). AB - The ferrous- and ferric-ion-promoted hydrolysis of the doxorubicin cardioprotective agent dexrazoxane (ICRF-187) has been studied spectrophotometrically and by HPLC. While dexrazoxane itself did not undergo any iron-promoted ring-opening hydrolysis, both ferrous (t1/2 0.4 min) and ferric (t1/2 170 min) ions promoted, by factors of up to 6000 and 8, respectively, the hydrolysis of the one-ring open intermediates of dexrazoxane to yield the strongly metal-ion-chelating form. The pH dependence of both the ferrous- and ferric-ion-promoted hydrolysis of one of the one-ring open intermediates was studied and was consistent with base-catalyzed hydrolysis. In each case, due to the problem of proton ambiguity in the rate law, a bimolecular reaction with external hydroxide could not be distinguished from an intramolecular reaction of hydroxide bound to iron. The mechanism of the cardioprotective effects of dexrazoxane may involve enzymatic or nonenzymatic hydrolysis to the one-ring open intermediates. Thus, these intermediates may be the active forms of the drug that may be acting by either displacing iron from the iron-doxorubicin complex or chelating loosely bound iron and then undergoing a rapid metal-ion-promoted hydrolysis to their strongly chelating forms. Thus, the ability of iron to participate in site-specific hydroxyl radical damage may be reduced. PMID- 7872774 TI - Structural analysis of invariant chain subsets as a function of their association with MHC class II chains. AB - Respective subsets of human invariant chain (Ii), as identified with antibodies to two different epitopes, were characterized as a function of their associations with major histocompatibility complex (MHC) class II alpha,beta chains and intracellular processing. E1 antiserum to Ii(183-193) and VIC-Y1 monoclonal antibody to an N-terminal determinant identified Ii(E1) and Ii(VIC) populations, respectively. Ii proteins comprise several species which have been defined with either genomic or post-translational processes: Ii itself; IpN and IpO, which represent the glycosylated forms on asparagine or threonine/serine, respectively; gamma 2 and gamma 3, which originate from an alternative initiation site for transcription; and p41, which has a 64-amino-acid insert which originated from an additional exon placed after the sixth exon of Ii. Immunoprecipitates of detergent-solubilized protein complexes from [35S]methionine-labeled Raji cells showed that Ii(E1) consisted of Ii, p41, IpN, and immature alpha chain, while Ii(VIC) consisted of Ii, processed Ii with N- and O-linked glycosylation (IpN,IpO), p41, and associated MHC class II alpha,beta chains. In the MHC class II-deficient P3HR-1 cells, Ii(E1) and Ii(VIC) were virtually identical. Ii(E1) was resistant to cathepsin B digestion while Ii(VIC) was sensitive. In pulse chase radiolabeling experiments with brefeldin A (BFA)-treated cells, Ii(VIC) progressively became resistant to endoglycosidase H (endo H) and had a longer half-life than that in cells not treated with BFA, but Ii(E1) remained susceptible to endo H and its half-life was unaffected by BFA. Since BFA redistributes Golgi enzymes to the endoplasmic reticulum, this observation suggests that Ii(E1) is protected from processing enzymes while Ii(VIC) is not. These studies define association of Ii with MHC class II molecules when certain epitopes on Ii are exposed or not. These differences relate to intracellular transport of Ii and to its release for the binding of antigenic peptides. PMID- 7872775 TI - Comparison of the effects of potassium on ouabain binding to native and site directed mutants of Na,K-ATPase. AB - We examined the effect of K+ on Mg(2+)- and P(i)-supported [3H]ouabain binding to Na,K-ATPases, including partially purified enzyme from sheep kidney and wild-type and mutant sheep alpha 1 isoforms (C104A, Y108A, E116Q, P118K, Y124F, R880P, R880L, and N122D) expressed in NIH3T3 cells. In the presence of increasing concentrations of K+, [3H]ouabain binding to these enzymes decreases but never reaches nonspecific binding levels, consistent with the concept that ouabain is still able to bind to the K(+)-complexed enzyme but with reduced affinity. A partially competitive model for K+ inhibition of ouabain binding is proposed which satisfactorily fits the binding data. The model is consistent with the sequential binding of two K+ ions to the enzyme. Ki values (approximately 1.0 mM) for K+ obtained from this model are comparable to the apparent K+ affinities of the rat alpha isoforms determined by measuring the K+ dependence of Na,K-ATPase activity [E. A. Jewell and J. B. Lingrel (1991) J. Biol. Chem. 266, 16925-16930]. This is consistent with the concept that K+ inhibition of Mg2+ plus P(i) supported ouabain binding is mediated by K+ binding to the same high-affinity binding sites present in the native enzyme under physiological conditions. While the mutants exhibit binding constants for ouabain which vary more than 30-fold from that of the wild-type enzyme, their affinities for K+ differ less than twofold from that of the native enzyme. Our results suggest that the ouabain and K+ binding sites are not the same and are differentially affected by mutations of the enzyme. The system described here should prove useful in the analysis of cation binding to other mutants of the Na,K-ATPase, especially those carrying amino acid replacements which result in an inactive enzyme. PMID- 7872776 TI - Hydroxylation of deoxyguanosine in DNA by copper and thiols. AB - DNA was incubated with glutathione (GSH) and copper and then assayed for 8 hydroxydeoxyguanosine (8-OHdG) in order to better understand the antioxidant and prooxidant characteristics of GSH in copper-dependent DNA damage. Ratios of GSH to Cu(II) less than 3 resulted in 8-OHdG production; however, higher ratios did not generate 8-OHdG. A combination of GSH and Cu(I) (10:1) was used to determine if DNA oxidation occurred upon the addition of H2O2. No increase in 8-OHdG was noted until the concentration of H2O2 was almost half that of GSH, and then a substantial increase of 8-OHdG was detected. The stoichiometry of thiol oxidation by H2O2 was 2 mol GSH oxidized per 1 mol H2O2. Oxidation of Cu(I) was not detected until most of the thiol had been oxidized. When cysteine and Cu(I) was used instead of GSH and Cu(I), there was considerable hydroxylation of deoxyguanosine. The glycyl carboxyl, the gamma-glutamate carboxyl, and the amine of GSH were altered to determine their role in the peptide's ability to inhibit Cu-dependent damage. In the presence of Cu(I), H2O2, and DNA, these GSH analogs behaved similarly to GSH. However, when S-methylglutathione was used in this system, it was very effective at promoting oxidative damage to DNA. This indicated that the thiol ligand of GSH was essential for inhibition of Cu dependent damage, while the carboxyl groups and the amine were not essential ligands. In conclusion, GSH can catalyze the in vitro hydroxylation of deoxyguanosine when the ratio of GSH to Cu is low, however, when the ratio is high GSH is an effective antioxidant. PMID- 7872777 TI - Isolation and characterization of an active-site peptide from a monoterpene cyclase labeled with a mechanism-based inhibitor. AB - (+)-Pinene synthase and (+)-bornyl pyrophosphate synthase from culinary sage (Salvia officinalis L.: Lamiaceae) catalyze the coupled isomerization and cyclization of geranyl pyrophosphate to the indicated bicyclic monoterpenes. The reaction parameters for these monoterpene cyclases have been well defined but the two enzymes have proved difficult to separate and purify in sufficient amounts for detailed structural characterization. A method was developed for the isolation of the two cyclases from highly enriched sage leaf oil gland extracts and for the efficient copurification of the two enzymes to about 95% as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE); the preparation yielded two overlapping species on two-dimensional polyacrylamide gel electrophoresis as expected. The cyclases were copurified and labeled with the highly selective mechanism-based irreversible inactivator 6-[1 3H]cyclopropylidene-3E-methyl-hex-2-en-1-yl pyrophosphate, subjected to cleavage with CNBr, and the resulting covalently modified peptides were isolated by SDS PAGE for blotting to a polyvinylidene difluoride membrane and N-terminal amino acid sequence analysis. A radiochemically abundant 5-kDa peptide of the cleavage mixture was shown to be highly homologous, through 22 residues, to a segment (Leu197-Glu218) of (-)-4S-limonene synthase from spearmint (Mentha spicata L.: Lamiaceae), the only monoterpene cyclase for which the complete deduced amino acid sequence is known. These results illustrate the use of the mechanism-based inhibitor for purification and structural studies with the monoterpene cyclases, and they define a presumptive active site region that bears a highly conserved sequence among these enzymes from the mint (Lamiaceae) family. PMID- 7872778 TI - Ubiquinone redox behavior in plant mitochondria during electron transport. AB - The redox poise of the ubiquinone pool during electron transfer in isolated soybean mitochondria has been compared using two different procedures: the rapid organic extraction of ubiquinone followed by quantification of the oxidized and reduced forms using high-pressure liquid chromatography and an electrochemical technique that measures ubiquinone reduction voltametrically. The goal of these studies was to rigorously test the use of the voltametric technique to monitor the redox status of ubiquinone during the course of mitochondrial electron transfer. The linear relationship between the two methods confirms the reliability of the data obtained with the voltametric technique; however, redox inactive pools of ubiquinone were detected with the HPLC technique. We also quantified the absolute amounts of the ubiquinone homologues ubiquinone-9 and ubiquinone-10 in mitochondria isolated from different soybean tissues and compared their behavior during electron transfer in the presence and absence of pyruvate, an allosteric effector of the cyanide-resistant electron transfer pathway. Both homologues belong to a common redox-active pool in the inner mitochondrial membrane. The results indicate that ubiquinone can be a limiting component of electron transfer through the cyanide-resistant pathway, particularly in roots where its concentration is much lower than in cotyledons. PMID- 7872779 TI - Biochemical characterization of lauric acid omega-hydroxylation by a CYP4A1/NADPH cytochrome P450 reductase fusion protein. AB - The binding and hydroxylation of lauric acid by a genetically engineered and expressed fusion protein comprised of an N-truncated form of rat CYP4A1 linked to an N-truncated form of rat NADPH cytochrome P450 oxidoreductase (OR) (constructed by Fisher et al., (1992) Proc. Natl. Acad. Sci. USA 89, 10817-10822) has been characterized biochemically and compared to that shown by purified reconstituted rat CYP4A1 and liver microsomes from clofibrate-induced rats. In all systems lauric acid induced a Type I cytochrome P450 difference spectrum with Ks values in agreement with prior literature (range 10-18 microM). When provided with NADPH and oxygen but no other proteins or lipid, the fusion protein (called f4A1) catalyzed omega-hydroxylation of lauric acid with apparent Km and Vm of 3-4 microM and 4-5 nmol product/min/nmol P450 irrespective of buffer concentration or cation (NaPi or KPi, 25-200 mM); comparable values for reconstituted CYP4A1 and microsomes from clofibrate-induced rats are 9 microM and 34 min-1 and 5 microM and 10 min-1, respectively. (omega-1)-Hydroxylation of lauric acid was barely detectable (omega/(omega-1) = 135) with f4A1 or with reconstituted CYP4A1, but it accounted for up to 50% of total products formed by microsomes from clofibrate induced rats. When added to the f4A1 system, OR stimulated hydroxylation up to fivefold at a OR:f4A1 ratio of 5:1; additionally, (omega-1)-hydroxylation was routinely observed as a minor process (< 4% of total product) in this system. These effects were also independent of buffer concentration. In contrast addition of cytochrome b5 (b5) caused a small (25%) decrease in omega-hydroxylation, while added phospholipid had no effect. However, the combination of OR, b5, and lipid stimulated turnover approximately 10-fold compared to f4A1 alone, and 11 hydroxylauric acid was regularly formed as a minor (3-4% of total) product. These observations indicate that the fusion protein f4A1 is functionally equivalent to reconstituted CYP4A1 with respect to binding and hydroxylation of lauric acid and suggest that it can be used as an alternative to reconstituted systems for structure-function and mechanistic studies of fatty acid omega-hydroxylation. PMID- 7872780 TI - Reaction of ascorbate with the alpha-tocopheroxyl radical in micellar and bilayer membrane systems. AB - The reaction by which the antioxidant capacity of alpha-tocopherol is sustained by recycling of the alpha-tocopheroxyl radical in membranes or lipoproteins by aqueous ascorbate has been studied by laser flash photolysis in model micellar and membrane systems. In bilayers of dimyristoylphosphatidylcholine at 35 degrees C the measured second-order rate constant was 3 x 10(5) M s-1, or about five times slower than previously reported in a solvent system. The rate of reaction was decreased on addition of negatively charged lipid (dipalmitoylphosphatidic acid) and increased by addition of positively charged lipid (didodecyldimethylammonium bromide). These effects of bilayer charge were suppressed by increasing the ionic strength of the aqueous medium. Micellar charge also had an effect on the pH dependence of the reaction rate. Arrhenius data showed that the enthalpy of activation was effectively zero for the reaction in solution between ascorbate and radicals of water-soluble tocopherol analogues, but was positive in membrane and micellar systems. In all cases the entropy of activation was strongly negative. The kinetic deuterium isotope ratio varied between 3 and 8. The data strongly support a concerted electron and proton transfer mechanism for the reaction between alpha-tocopheroxyl radical and ascorbate. PMID- 7872781 TI - Reevaluation of the pathway for the metabolism of 7,10,13, 16-docosatetraenoic acid to 4,7,10,13,16-docosapentaenoic acid in rat liver. AB - When rat liver microsomes were incubated with [1-14C]22:4(n-6) under standard conditions for measuring acyl-CoA desaturases, it was not possible to detect the synthesis of any 22:5(n-6). When malonyl-CoA and NADPH were included in the incubation, 22:4(n-6) was chain elongated to 24:4(n-6), which was then desaturated to 24:5(n-6). Rat hepatocytes metabolized [1-14C]22:4(n-6), [3 14C]24:4(n-6), and [3-14C]24:5(n-6) to yield esterified radioactive 22:5(n-6). The results show that 22:4(n-6) is the precursor of 22:5(n-6) but the pathway is independent of an acyl-CoA-dependent 4-desaturase and probably requires intracellular communication between the endoplasmic reticulum and a site for beta oxidation. Microsomal reaction rates for (n-6) versus (n-3) polyunsaturated fatty acid biosynthesis cannot per se be used to explain why in vivo most membrane lipids preferentially accumulate 22:6(n-3) rather than 22:5(n-6). Rates of desaturation of 24:4(n-6) and 24:5(n-3) at position 6 were similar (M. Geiger et al., Biochim. Biophys. Acta 1170, 137-142, 1993). We now show that 20:4(n-6) and 20:5(n-3) are chain elongated at the same rate as are 22:4(n-6) and 22:5(n-3). At present, no single reaction can be defined as being substrate specific or rate limiting to explain why there is an apparent selective synthesis and acylation of 22:6(n-3) rather than 22:5(n-6) into membrane lipids. PMID- 7872782 TI - Alteration of acyl-acyl carrier protein pools and acetyl-CoA carboxylase expression in Escherichia coli by a plant medium chain acyl-acyl carrier protein thioesterase. AB - Expression of a plant lauroyl-acyl carrier protein (ACP) thioesterase in an Escherichia coli strain deficient in beta oxidation results in the accumulation of free fatty acids in the culture. Overall fatty acid production by the cultures is increased severalfold, particularly in the late log and stationary stages of growth. In control E. coli cells, malonyl-ACP levels and rates of fatty acid synthesis are highest during rapid logarithmic growth and decline to undetectable levels in stationary stage. In contrast, in cells expressing plant acyl-ACP thioesterase, malonyl-ACP levels remain high in late log and stationary stage in association with the continued fatty acid production. In addition, the biotin carboxyl carrier protein component of acetyl-CoA carboxylase is expressed at higher levels in cultures expressing the acyl-ACP thioesterase. The data presented indicate that removal of the acyl-ACP products of fatty acid synthesis results in increased production of both malonyl-ACP and fatty acids, which may in turn result from higher activity and/or expression of acetyl-CoA carboxylase. PMID- 7872783 TI - Selective inhibition of prostaglandin endoperoxide synthase-1 (cyclooxygenase-1) by valerylsalicylic acid. AB - Aspirin causes a time-dependent inhibition of prostaglandin endoperoxide H synthases (PGHS)-1 and -2 by acetylating active site serines present in both isozymes. In the case of PGHS-1, aspirin acetylation blocks cyclooxygenase activity, apparently by preventing arachidonate binding to the cyclooxygenase active site. With PGHS-2, acetylation does not block substrate binding but rather alters the enzyme in such a way that the acetylated form of PGHS-2 produces 15R hydroxyeicosatetraenoic acid (15R-HETE) instead of the usual prostaglandin endoperoxide product. Based on these differences between PGHS-1 and PGHS-2, we reasoned that a salicylate ester containing an acyl group somewhat larger than the acetyl group of aspirin might be a selective inhibitor of PGHS-2. Accordingly, we prepared and tested eight different acyl salicylates as inhibitors of human (h) PGHS-1 and -2 expressed transiently in cos-1 cells. Valeryl(pentanoyl)salicylate (VSA) was the only compound in this series which showed isozyme selectivity, and, surprisingly, VSA inhibited hPGHS-1 much more effectively than hPGHS-2. Inhibition of hPGHS-1 by VSA was time-dependent. VSA also inhibited ovine PGHS-1 but did not inhibit the S530A mutant of ovine PGHS-1. This latter mutant, which lacks the active site serine hydroxyl group, is also refractory to inhibition by acetylsalicylate. Thus, we conclude that VSA acylates the active site serine of PGHS-1. VSA inhibited prostanoid synthesis by serum starved murine NIH 3T3 cells which express only PGHS-1; in contrast, VSA caused only partial inhibition of prostanoid synthesis by serum-stimulated 3T3 cells which express both PGHS isozymes. Our results establish that VSA can be used as a reasonably selective inhibitor of PGHS-1. PMID- 7872784 TI - Changes in protein sulfation in human erythroleukemia (HEL), CHRF-288-11, and K562 cells following treatment with dimethyl sulfoxide or phorbol 12-myristate 13 acetate. AB - This study has demonstrated that three hematopoietic tumor cell lines with megakaryocytic characteristics, HEL, CHRF-288-11, and K562, synthesize a number of sulfated proteins. The major HEL sulfated proteins were a doublet at 88 and 92 kDa and several closely spaced bands between 125 and 160 kDa and more acidic proteins of 210 kDa. Treatment with dimethylsulfoxide (DMSO) for 24 h almost completely inhibited labeling of sulfated proteins, and up to 48 h, labeling was found almost entirely in a band at 125 kDa. Treatment with phorbol 12-myristate 13-acetate (PMA) nearly eliminated labeling of the 88- and 92-kDa bands and resulted in the appearance of a large amount of labeling between 96 and 108 kDa. Sulfated proteins of 135 and 210 kDa were immunoprecipitated by an antibody against platelet GP Ib. A 130-kDa protein was immunoprecipitated by an antibody against the beta-1 integrin subunit. The major proteins labeled in CHRF cells were at 68, 90, 98, 125, and 148 kDa. Treatment with PMA greatly reduced the labeling of the 148-kDa band, eliminated the labeling of the 68-kDa band, and markedly enhanced labeling of the 92-kDa region. The major proteins labeled in K562 cells were at 110, 120-130, and 145 kDa. PMA reduced the labeling of the 110 and 145-kDa proteins and extensively increased labeling of bands at 120-130, 78, and 84 kDa, and DMSO caused decreased labeling of the 120- to 130-kDa proteins. This is the first demonstration of sulfation of specific proteins in hematopoietic cell lines and of the alteration of sulfation of specific proteins in any cells in response to treatment with differentiation-inducing agents. We hypothesize that changes in sulfation of proteins may be relevant to the maturation or malignant growth of megakaryocytic cells. PMID- 7872785 TI - The inducible 9, 10-dihydrophenanthrene pathway: characterization and expression of bibenzyl synthase and S-adenosylhomocysteine hydrolase. AB - Tricyclic 9,10-dihydrophenanthrenes originate from phenylpropane derivatives by chain elongation and cyclization according to the polyacetate rule. Bibenzyls are bicyclic intermediates, and O-methylation is a prerequisite for their conversion into dihydrophenanthrenes. cDNA clones encoding bibenzyl synthases and S adenosylhomocysteine hydrolase of the orchid Phalaenopsis sp. were isolated from a cDNA library representing the stage of elicitor-induced plants. The deduced amino acid sequences of two clones, pBibSy811 and pBibSy212, indicated that we obtained two full-length sequences of bibenzyl synthases characterized by their homology to stilbene synthases previously investigated. That indeed bibenzyl synthase cDNAs rather than a homologous stilbene synthase cDNA or chalcone synthase cDNA have been isolated was demonstrated by expression of two enzymatically active bibenzyl synthase proteins in Escherichia coli. These proteins showed virtually the same selectivity towards m-hydroxyphenylpropionyl CoA as substrate as the enzyme isolated from orchid plants. In young sterile Phalaenopsis plants, the formation of both bibenzyl synthase mRNAs and S adenosylhomocysteine hydrolase mRNAs was increased upon elicitation more than 100 fold. The time courses of gene expression exhibited transient profiles, reaching maximum mRNA levels 20 h after onset of fungal infection followed by a rapid decline to 40 h. PMID- 7872786 TI - Ascorbic acid transport and distribution in human B lymphocytes. AB - Ascorbic acid (vitamin C) transport was investigated in human B lymphocytes. The vitamin was transported by two components. The first was a high-affinity activity with an apparent Km of 7-10 microM and Vmax of 0.14 mM/h (3.11 x 10(-4) mumol x h 1 x mg protein-1). The activity was concentration and temperature dependent, saturable, and inhibited by carbonylcyanide-p-trifluoromethoxyphenylhydrazone and ouabain and generated ascorbic acid accumulation against a concentration gradient. Kinetics for the second component were indeterminate because ascorbate was not accumulated against a concentration gradient. Subcellular fractionation revealed that intracellular ascorbic acid in human B lymphocytes was > 90% localized to the cytosol and not protein bound. Kinetic parameters of high affinity ascorbic acid transport could operate effectively with plasma concentrations normally found in humans. PMID- 7872787 TI - Functional complementation of the mvrA mutation of Escherichia coli by plant ferredoxin-NADP+ oxidoreductase. AB - Escherichia coli cells carrying the mvrA mutation are unable to grow aerobically in the presence of the radical propagator methyl viologen (MV). Resistance against MV toxicity could be restored by the introduction of cloned DNA sequences encoding pea chloroplast ferredoxin-NADP+ reductase (FNR), a member of a class of flavoenzymes involved in redox pathways in bacteria, plants and animals. Complementation was strictly dependent on the accumulation of a functional transgenic FNR, since mutated reductases showing decreased enzymatic activities only partially rescued the MV-resistant phenotype. These results support recent observations suggesting that the E. coli mvrA gene encodes a ferredoxin (flavodoxin)-NADP+ reductase (V. Bianchi et al. (1993) J. Bacteriol. 175, 1590 1595). The mvrA mutant cells showed a moderate decrease in the flavodoxin dependent activation of enzymes essential for anaerobic growth of E. coli. This effect is prevented by expression of a functional pea FNR in the mutant cells. PMID- 7872788 TI - Cloning and expression of hydrolase C, a member of the rat carboxylesterase family. AB - Using polymerase chain reaction (PCR), we have isolated a cDNA that encodes a rat liver carboxylesterase. This novel enzyme, designated hydrolase C, is structurally very similar to hydrolase B, a microsomal carboxylesterase expressed in rat liver and kidney. Hydrolase B and C are 96% identical in nucleotide sequence and 93% identical in deduced amino acid sequence. Both enzymes have an 18-amino-acid signal peptide at the N-terminus. The C-terminus of hydrolase B and C contains an HXEL consensus sequence for retaining proteins in the endoplasmic reticulum. As expected, when the cDNA encoding hydrolase C was expressed in a baculovirus/Sf21 cell system, the recombinant enzyme was localized in the endoplasmic reticulum. Hydrolase B and C both have putative N-linked glycosylation sites at Asn1 and Asn61. The active site of hydrolase B and C appears to be composed of a nucleophile, Ser203, a basic residue, His448, and an acidic residue, either Asp97 or Glu228. Based on cloning experiments, restriction endonuclease mapping and Northern blotting, hydrolase B is expressed in both rat liver and kidney, whereas hydrolase C is expressed predominantly, perhaps exclusively, in liver. When expressed in Escherichia coli, hydrolase C was catalytically inactive and unstable, but when expressed in the baculovirus/Sf21 cell system hydrolase C it was stable and catalytically active toward 1 naphthylacetate and esters of para-nitrophenol. Hydrolase C is the fourth member of the rat carboxylesterase family to be cloned and sequenced. In terms of nucleotide and deduced amino acid sequence, hydrolase C is highly similar to hydrolase B, but differs from hydrolase B in terms of its catalytic activity and tissue distribution. Recombinant hydrolase C has properties similar to those described for esterase RL2, which was purified from rat liver microsomes by Hosokawa et al. (Arch. Biochem. Biophys. 277, 219-227, 1990), although additional studies will be required to establish conclusively the identity of this enzyme. The high degree of sequence identity (96%) between hydrolase B and C, particularly in the 3' untranslated region, suggests that the genes encoding these two carboxylesterases evolved by duplication and divergence of a common ancestral gene. PMID- 7872789 TI - Post-transcriptional regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by mevalonate. AB - We have examined the mechanisms of sterol-independent regulation of the expression of 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase by mevalonate in Chinese hamster ovary (CHO) cells. Serum lipoproteins, 25 hydroxycholesterol, or mevalonate each repress HMG-CoA reductase activity by fivefold or more, and mevalonate lowers the rate of reductase synthesis by twofold. However, while the expression of the HMG-CoA reductase promoter construct, T42 delta CAT, in stable transfectants is also repressed by serum lipoproteins and 25-hydroxycholesterol, mevalonate is without effect. In addition, while 25-hydroxycholesterol reduces the steady-state level of endogenous HMG-CoA reductase mRNA by more than threefold, mevalonate again has no effect. Mevalonate does partially regulate the expression of both the artificial promoter construct pTK-Kx3-CAT, containing three copies of the sterol regulatory element, SRE-1, and the full-length LDL receptor promoter construct, pLDLRCAT 6500 as well as the expression of functional LDL receptors. This transcriptional regulation appears to be mediated by sterol end products generated from added mevalonate. In CHO cells starved for mevalonate due to a mutation in the biosynthetic pathway, addition of 20 mM mevalonate accelerates the rate of degradation of HMG-CoA reductase by threefold whether new sterol biosynthesis is blocked or not. In such cells, addition of 25-hydroxycholesterol, by itself, also decreases the half-life of reductase from 11.6 to 2.3 h. In contrast, in cells acutely treated with a reductase inhibitor, sterol-accelerated degradation of reductase is only observed in the presence of submillimolar level of mevalonate. We conclude that large concentrations of exogenous mevalonate fail to generate a transcriptional regulator of HMG-CoA reductase in CHO cells but do lead to the formation of translational regulator(s) of reductase synthesis. In contrast, sterol regulators derived from exogenous mevalonate appear to be capable of downregulating the LDL receptor promoter. We further conclude that in the absence of pretreatment with a reductase inhibitor, the regulatory signals generated by sterols and nonsterols for accelerated degradation of HMG-CoA reductase are mutually independent. However, the enzyme synthesized in the presence of reductase inhibitors appears to exhibit an obligatory corequirement for low-dose mevalonate for sterol-accelerated degradation. PMID- 7872790 TI - Properties of fructose-1,6-bisphosphate aldolase from Escherichia coli: an NMR analysis. AB - A class II Zn(2+)-dependent fructose-1,6-bisphosphate (FBP)- aldolase was purified from an overproducer strain of Escherichia coli and characterized by standard biochemical techniques and 13C NMR spectroscopy. The principal finding of these studies was identification, by 13C NMR spectroscopy, of an enzyme-bound reaction intermediate, the enediol(ate) form of dihydroxyacetone phosphate (DHAP). Formation of this intermediate requires the presence of Zn2+ and is pH dependent, with increasing amounts of this tautomer appearing at alkaline pH's. This pH dependence closely parallels the pH activity profile of the enzyme, suggesting an involvement of the enediol-DHAP form in the reaction pathway. In addition to these results the following observations were made on this enzyme: (a) E. coli FBP aldolase binds and utilizes only the carbonyl forms of FBP and DHAP; (b) the function of Zn2+ in this metalloaldolase appears to be polarization of the C = O bond of DHAP; (c) activity of this enzyme is unaffected by glycolytic intermediates or nucleotide phosphates such as ATP. Although these studies provide some information about the catalytic mechanism of E. coli FBP aldolase, they do not provide an explanation for the apparent regulation of this enzyme reported in previous in vivo NMR studies. While the possibility that the enzyme is allosterically regulated cannot be excluded at this time, an interesting possibility suggested by this and other studies is that in E. coli glycolytic substrates may be channeled through a multienzyme complex. PMID- 7872791 TI - Molecular states of fungal nuclease composed of heterogeneous subunits as estimated from the effects of urea and chelating agents. AB - Fungal nuclease composed of subunits with molecular weights of 8.0 x 10(4) (80K subunit), 5.0 x 10(4) (50K subunit), and 2.5 x 10(4) (25K subunit) (K. Ito, Y. Matsuura, and N. Minamiura (1994) Arch. Biochem. Biophys. 309, 160-167) was inactivated by urea and dissociated into its subunits. The urea inactivation depended on the concentration of urea, the incubation period and the temperature. The urea-inactivated enzyme had about 25% activity restored by removal of urea, and the native form of the enzyme was also reconstituted. The urea inactivation and the dissociation of subunits were almost completely prevented by Ca2+ but not by glycerol. The enzyme was also inactivated by ethylenediaminetetraacetic acid (EDTA). From this method of inactivation, the 50K and 25K subunits were still associated, but the complex showed no nuclease activity. About 80% of the activity of the EDTA-inactivated enzyme was restored by the addition of Ca2+ or Sr2+ and 20-40% by Mn2+, Ba2+, Mg2+, or Co2+. The reactivation of the enzyme by these metal ions was accompanied by the reconstitution of the native form of the enzyme. The enzyme was inactivated by ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA) at much higher concentrations compared with the inactivation by EDTA. On the other hand, dissociation of the subunits by EGTA proceeded in a manner similar to that of the inactivation of the enzyme by EDTA. The 50K and 25K subunits were still associated, and the complex showed nuclease activity. These results indicated that the enzyme contains two kinds of metal ions. One metal ion, represented by Ca2+, is thought to stabilize the quanternary structure of the enzyme, especially to connect the 80K subunit and the complex of the 50K and 25K subunits. Another metal ion, represented by Mg2+, is thought to be bound to the complex of the 50K and 25K subunits and to be required for activity appearance of the complex. Along with these results, possible molecular states of the enzyme under various conditions are proposed. PMID- 7872792 TI - Demonstration that histidine 25, but not 132, is the axial heme ligand in rat heme oxygenase-1. AB - A truncated, soluble rat heme oxygenase-1 lacking its C-terminal, membrane anchoring segment, and its His25-->Ala and His132-->Ala mutants have been prepared by site-directed mutagenesis and expression in Escherichia coli. We found that wild-type enzyme can degrade heme to biliverdin, but its specific activity was about one-fifth that of the native, full-length enzyme, suggesting that the C-terminal segment is important for accepting electrons from NADPH cytochrome P450 reductase. His132-->Ala mutant had an enzyme activity comparable to that of the wild-type enzyme; hence, the highly conserved His132 is not essential for the display of the heme oxygenase activity. In contrast, His25- >Ala mutation completely abolished the enzyme's catalytic activity. A five coordinate type ferrous NO EPR spectrum was observed for the heme-heme oxygenase H25A complex. Hence, we conclude that His25 is the proximal axial ligand of the heme iron and is essential for the heme degradation activity of the enzyme. PMID- 7872793 TI - Dimerization of native and C-terminally proteolyzed p56lck tyrosine kinase. AB - Recombinant p56lck tyrosine kinase was purified to near homogeneity from a baculovirus/insect cell expression system. Treatment with thrombin proteolytically removed the C-terminal 54 amino acids from p56lck. Processed enzyme migrated on sodium dodecyl sulfate (SDS) gels with a M(r) approximately 6,000 lower than intact enzyme. Analytical ultracentrifugation of intact and processed p56lck gave M(r)'s of 62,600 and 56,200, respectively, confirming that the thrombin treated enzyme existed in solution as a processed polypeptide and that there was no anomalous migration in SDS gels due to thrombin treatment. Simultaneous multispeed analysis of sedimentation equilibrium data demonstrated that both intact and processed enzyme can dimerize with a weak binding constant in the range of 200-300 microM. Purified intact p56lck incorporated 2 mol of [32P]P(i) per mole of enzyme. Purified processed p56lck incorporated only 1 mol of [32P]P(i) per mole of enzyme. The loss of 1 mol of [32P]P(i) per mole of enzyme after thrombin deletion of the C-terminus demonstrates that p56lck undergoes autophosphorylation at the C-terminus. The data are consistent with autophosphorylation at tyrosine 505, which has previously been thought to be a regulatory phosphorylation site, but which now must also be considered as an autophosphorylation site. PMID- 7872794 TI - A 3' untranslated region of catalase mRNA composed of a stem-loop and dinucleotide repeat elements binds a 69-kDa redox-sensitive protein. AB - Rat lung extract contains protein that forms redox-sensitive, specific complexes with a 1130-base catalase cRNA (J. Biol. Chem. 267, 2853-2855, 1992). The present paper reports studies aimed at delimiting the site of protein binding on the RNA and characterizing the protein. A 240-base sequence was identified as the 3' untranslated region of catalase mRNA that binds lung protein in a redox-sensitive manner. Two elements within this 240-base region bind protein; one is a 36-base element that has a computer-predicted stem-loop secondary structure and the other is a CA dinucleotide repeat. Competition studies indicate that both elements are required for specific binding. Cross-competition experiments demonstrated that catalase RNA-binding protein (CAT-BP) is not the iron-responsive element-binding protein. Ultraviolet light-induced cross-linking and two-dimensional electrophoresis showed that CAT-BP has an apparent molecular mass of 69 kDa and appears to be composed of four isoforms. Competition studies indicate that stem loop cis element is directly involved in binding CAT-BP. In addition to rat, the 69-kDa catalase RNA-binding protein is present in mouse and human fibroblast cell lines. PMID- 7872795 TI - Characterization of flavin-containing monooxygenase 5 (FMO5) cloned from human and guinea pig: evidence that the unique catalytic properties of FMO5 are not confined to the rabbit ortholog. AB - Several full-length clones encoding the human and guinea pig orthologs of flavin containing monooxygenase 5 (FMO5) have been isolated from libraries constructed with hepatic mRNA. The clones were detected by hybridization with the cDNA encoding FMO5 expressed in rabbit. The human and guinea pig cDNAs encode for proteins of 533 amino acids that contain putative pyrophosphate binding domains characteristic of mammalian FMOs. The sequences derived for the human and guinea pig FMO5 proteins are 87% identical and are 85 and 82% identical, respectively, to the sequence of rabbit FMO5. As is the case with other FMOs, FMO5 in human and guinea pig is encoded by multiple transcripts. Rabbit FMO5 expressed in Escherichia coli was purified and used to elicit antibodies in goat. These antibodies detected FMO5 in samples from livers of adult humans, rabbits, and guinea pigs and fetal livers of humans. The human and guinea pig forms of FMO5 were expressed in E. coli and characterized. Neither enzyme effectively catalyzed the metabolism of methimazole, a general FMO substrate; however, both were active with n-octylamine. The responses of the human FMO5 and guinea pig FMO5 to detergent, ions and elevated temperature are all similar to the responses described for rabbit FMO5. These results indicate that the unique properties of FMO5 from rabbit are species-independent and that this form of the flavin containing monooxygenase is not readily classified as a drug-metabolizing enzyme. PMID- 7872796 TI - High-performance liquid chromatographic purification, optimization of the assay, and properties of ribonucleoside diphosphate reductase from rabbit bone marrow. AB - Partial purification of ribonucleoside diphosphate reductase from rabbit bone marrow was achieved by size exclusion HPLC of the crude homogenate. This step, requiring < 15 min, led to 9- to 13-fold purification of the reductase and removal of 64% of the contaminating kinase/phosphatase activities, which in the crude extract degrade > 95% of substrate CDP when reductase is assayed. A systematic study was conducted to evaluate the influence of contaminating kinase/phosphatase activities on CDP concentration during the reductase-catalyzed reaction with either ATP or its kinase-inhibiting analog, 5' adenylylimidodiphosphate (AMP-PNP), as the allosteric effector. Our studies demonstrated that in the presence of ATP, CDP levels fell instantly to < 24% but thereafter remained fairly constant due to recycling via CTP. In contrast, in the presence of AMP-PNP, CDP levels decreased continuously. The Km values of the reductase for CDP determined in the presence of ATP were significantly higher than those in the presence of AMP-PNP. Furthermore, we also found that the concentration of the ultimate electron donor dithiothreitol (DTT) required for optimum activity of the reductase varies significantly with the level of purity of the reductase preparation. Interestingly, DTT is an inhibitor of the reductase above the optimum concentration. This purification method and the optimized assay together with the understanding of the fate of CDP in partially purified preparations should find application in studies with reductases from other eukaryotic sources. PMID- 7872797 TI - Probing the active sites of rat and human cytochrome P450 2E1 with alcohols and carboxylic acids. AB - Cytochrome P450 2E1 (P450 2E1) catalyzes the biotransformation of many low molecular-weight compounds including industrial solvents, indoor pollutants, alcohol, and drugs. In order to understand the nature of the P450 2E1 active site, we studied the competitive inhibition of the P450 2E1-catalyzed N nitrosodimethylamine demethylation by alcohols and carboxylic acids with different alkyl chain lengths. Using microsomes from acetone-treated rats as the enzyme source of P450 2E1, the Ki value for each compound was measured. With primary alcohols and secondary alcohols, the Ki decreased with the increase in the carbon chain length until the carbon number reached 6 or 7; the free energy increment of binding was 0.28 kcal/mol CH2 group. Similar inhibitory effects were also observed with human P450 2E1 heterologously expressed in Hep G2 cells. These results suggest that both rat and human P450 2E1 contain a pocket with hydrophobicity that serves as a binding site for low-molecular-weight substrates. Among a series of carboxylic acids and omega-hydroxycarboxylic acids investigated, dodecanoic acid was the strongest inhibitor (Ki = 22 microM), and 12-hydroxydodecanoic acid had the lowest Ki (320 microM) within the series of omega-hydroxycarboxylic acids. The free energy increment of binding for carboxylic acids was 0.35 kcal/mol CH2 group. 1,10-Decanedicarboxylic acid, which contains a carboxylic group at each end, showed a Ki > 20 mM. We suggest that for optimal interaction of a carboxylic acid moiety with the active site of P450 2E1, the hydrocarbon end of the molecule binds to the substrate binding site, leaving the carboxylic acid group outside of a proposed substrate access channel. The length of optimal substrates such as dodecanoic acid may reflect the length of the substrate access channel and the size of the active site. We estimate that the distance from the opening of the access channel to the oxygenation site is about 15 A. Based on the structural features of P450 2E1 substrates and competitive inhibitors, we propose a conceptual model to illustrate the binding of these molecules in the active site of P450 2E1. PMID- 7872799 TI - Novel extracellular matrix-associated serine proteinase inhibitors from human skin fibroblasts. AB - Serine proteinase inhibitors play a major role in the turnover of connective tissues. In this study, we isolated and determined partial amino-terminal amino acid sequence of trypsin/elastase/plasmin inhibitors (M(r) 33,000 and 31,000) from the extracellular matrix of SV40-transformed human skin fibroblasts. The antitrypsin activity of the inhibitors was monitored by substrate reverse zymography. Polyclonal antisera to alpha 1-antitrypsin, alpha 1-antichymotrypsin, alpha 2-antiplasmin, inter-alpha-trypsin inhibitor, plasminogen activator inhibitors-1 and -2, and a monoclonal antibody to protease nexin-1 did not label the 33-, 31-, and 27-kDa inhibitors. A computer search for amino acid sequence homology indicated that the 31-kDa inhibitor is novel. In contrast, the sequence of the 33-kDa inhibitor shared 70 to 90% homology with the amino-terminal sequence of a recently characterized 32-kDa trypsin/tissue factor inhibitor called tissue factor pathway inhibitor-2. The 33- and 31-kDa inhibitors bind to heparin-Sepharose and were recovered from the affinity beads as well as from the t12 FB extracellular matrix with 1 M NaCl. Based on these results, we propose that the extracellular matrix of human mesenchymal cells sequester a family of novel serine proteinase inhibitors. PMID- 7872798 TI - Synthesis and secretion of procathepsin B and cystatin C by human bronchial epithelial cells in vitro: modulation of cathepsin B activity by neutrophil elastase. AB - Procathepsin B and cystatin C are found in human lung secretions. We investigated the capacity of human bronchial epithelial cells to synthesize and secrete these proteins. Immunoprecipitation of [35S]methionine-labeled proteins from cultured bronchial epithelial cell lysates, followed by denaturing gel electrophoresis and autoradiography, showed the presence of newly synthesized procathepsin B of M(r) 42,000; no mature form was detected. Cathepsin B in conditioned medium from epithelial cells was tagged with benzyloxycarbonyl-125I-tyrosyl-alanine diazomethane before and after treatment of the medium with neutrophil elastase. Control medium again showed a predominant form of cathepsin B with a M(r) of 42,000, but upon treatment with neutrophil elastase this protein was converted to a M(r) of 38,000, similar to the active form previously found in lung secretions, and cathepsin B activity was generated. The medium also contained the cathepsin B inhibitor, cystatin C, but cystatins A, B, S, SN, SA, and kininogen were not detected. After removal of cystatin C from the medium, elastase was still required to activate procathepsin B. These results suggest that bronchial epithelial cells are a source of procathepsin B and cystatin C in lung secretions. Cleavage both of cystatin C and procathepsin B by neutrophil elastase is essential for the generation of cathepsin B activity in the medium. PMID- 7872800 TI - Intrinsic fluorescence of the chloroplast H(+)-ATPase. AB - We have examined the intrinsic fluorescence properties of a highly purified chloroplast H(+)-ATPase (CF0F1) preparation [R. D. Kirch and P. Graber (1992) Acta Physiol. Scand. 746, 9-12). Unlike the catalytic CF1 portion alone, CF0F1 fluorescence was dominated by tryptophan fluorescence both at 277-nm excitation, favoring tyrosine excitation, and at 295-nm excitation, favoring tryptophan excitation. A broad tryptophan fluorescence peak was observed with a maximum at around 335 nm and a broad shoulder around 350 nm. Denaturation of the enzyme complex with guanidine-HCl resulted in a significant increase (approximately 40%) in tyrosine fluorescence. The fluorescence spectrum (lambda ex = 295 nm) of the inhibitory epsilon subunit isolated from CF1 resembled that of CF1, indicating the presence of two tryptophan species located in different environments. Fluorescence quenching by potassium iodide indicated a substantial increase in the solvent accessibility of one of the two tryptophans following isolation of epsilon from CF1. Thus, when epsilon binds to CF1, a tryptophan residue becomes partially buried, probably at an interface between epsilon and another (possibly gamma) CF1 subunit. Removal of the epsilon subunit from CF1 leads to an increase in tyrosine fluorescence of a magnitude similar to that obtained upon denaturation of the CF0F1 complex. The results suggest that the reversible association of the epsilon subunit with CF0F1 or with isolated CF1 may be monitored by following changes in the intrinsic fluorescence of the enzyme complex. PMID- 7872802 TI - Prediction of pH-dependent properties of DNA triple helices. AB - The thermodynamic properties of two triple helices were investigated by uv thermal denaturation, differential scanning calorimetry, and pH titrations. Starting from the grand partition function and using matrix methods we present a formalism that describes pH effects on the thermal stability of triple helices. The formalism can be used over a wide pH range and is not restricted to the limiting case where the pH is larger or smaller than the pK alpha of cytosine. Furthermore, it covers nearest neighbor electrostatic effects of closely spaced cytosines in the Hoogsteen strand which can shift the pK alpha of cytosine to lower pH values. A procedure is employed to predict enthalpy and entropy changes for triplex formation. These values are in accordance with the results obtained by differential scanning calorimetry. PMID- 7872801 TI - Characterization of a negative cis-acting DNA element regulating the transcription of CYP2B1/B2 gene in rat liver. AB - The region -160 to -127 nt of the upstream of CYP2B1/B2 gene has been found to function as a negative cis-acting element on the basis of DNase-I footprint and gel mobility shift assays as well as cell-free transcriptional assays using Bal 31 mutants. A reciprocal relationship in the interaction of the negative and the recently characterized positive elements with their respective protein factors has been found under repressed and induced conditions of the gene. The negative element also harbors the core glucocorticoid responsive sequence, TGTCCT. It is concluded that the negative element mediates the repressed state of the gene under the uninduced condition and also mediates the repressive effect of dexamethasone, when given along with the inducer phenobarbitone in rats. Dexamethasone is able to antagonize the effects of phenobarbitone at as low a concentration as 100 micrograms/kg body wt in these animals. PMID- 7872803 TI - Superoxide dismutase protects Escherichia coli against killing by human serum. AB - To assess the role of superoxide dismutase in protecting Escherichia coli from killing by human serum and neutrophils, we constructed isogenic, smooth lipopolysaccharide K-12 strains, either sod wild-type, delta sodA, or delta sodA delta sodB. The delta sodA delta sodB strain was killed by serum much more readily than either the wild-type or delta sodA strain. After allowing for this serum sensitivity difference, the delta sodA delta sodB strain also showed increased susceptibility to phagocytic killing by human neutrophils. These results indicate that superoxide dismutase protects E. coli from killing by serum (complement system) and by human neutrophils, possibly by a role in maintaining bacterial membrane structure. PMID- 7872804 TI - Expression of mouse uterine peptidylarginine deiminase in Escherichia coli: construction of expression plasmid and properties of the recombinant enzyme. AB - To study the structure/function relationships of peptidylarginine deiminase (PAD), we constructed an Escherichia coli expression plasmid for mouse uterine PAD. First, segments of a cDNA encoding murine PAD were subcloned into a single plasmid, and the resulting plasmid, pKSPAD1, was inserted into an expression vector, pKK223-3, at the EcoRI and HindIII restriction sites. Since no detectable amount or activity of the PAD was produced by E. coli carrying that plasmid, the 5'-untranslated sequence of the cDNA was replaced with several synthetic DNAs. One of the constructed plasmids, pKKPAD4, which had a unique DNA linker containing a pair of Shine-Dalgarno sequences and a short preceding cistron inserted into the adjacent 5'-region of the coding region, produced a large quantity of mouse PAD as an unfused protein in E. coli. The purified recombinant PAD was indistinguishable from the native enzyme with respect to some structural properties, such as molecular mass, amino- and carboxyl-terminal sequences, and circular dichroism spectra. However, the alpha-amino group of the amino-terminal methionine residue of the recombinant PAD was not acetylated as was that of the native enzyme. Comparison of the recombinant PAD with the natural enzyme did not indicate significant differences in their sensitivity to activation by Ca2+ and in their substrate specificity toward arginine derivatives. The rates of modification of soybean trypsin inhibitor (Kunitz) were also similar for the recombinant and native PADs. These results indicate that the recombinant PAD has biological activities identical to those of the native enzyme and that the N alpha-acetyl group in the native PAD does not appear to have any particular role in the enzyme's catalytic function. PMID- 7872805 TI - A novel chymotrypsin-like component of the multicatalytic proteinase complex optimally active at acidic pH. AB - The multicatalytic proteinase complex (MPC) or proteasome is a multimeric, high molecular-weight (700,000), extralysosomal proteolytic enzyme found in eukaryotes and in archaebacteria. Its multiple catalytic sites grant it a broad cleavage specificity toward short peptides and protein substrates. The pH optima of the catalytic activities of MPC are in the neutral or slightly alkaline range. We present here evidence for cryptic catalytic components of MPC optimally active at an acidic pH. Studies with a hydrophobic fluorescent probe provide direct evidence for conformational changes brought about by exposing the complex to an acidic environment. One of the newly described components, designated "acidic chymotrypsin-like activity," cleaves the Leu-2-naphthylamide bond in the substrate Boc-Val-Glu-Ala-Leu-2-naphythylamide. Compared with the classical "neutral" chymotrypsin-like activity defined by cleavage of the Leu-p nitroanilide bond in Z-Gly-Gly-Leu-p-nitroanilide, the newly described component is not inhibited by monovalent cations and is less sensitive to the peptidyl aldehyde Z-Gly-Gly-leucinal, an inhibitor of the neutral chymotrypsin-like activity. In addition, we describe the properties of a novel potent peptidyl aldehyde, Z-Ile-Glu(OtBu)-Ala-leucinal, which is an inhibitor of both the acidic and neutral chymotrypsin-like activities of MPC, with IC50 values of 0.25 and 6.5 microM, respectively. In the presence of 65 microM of the newly synthesized peptidyl aldehyde, other MPC components such as the trypsin-like and peptidyl glutamyl peptide hydrolyzing activities were decreased only by 14 and 9%, respectively. The hydrophobicity, potency, and specificity of Z-Ile-Glu(OtBu)-Ala leucinal toward the chymotrypsin-like activities of the complex make it a valuable pharmacological tool with which to investigate the physiological roles of MPC. PMID- 7872806 TI - Amplification and hyperexpression of the catalase gene in selenoperoxidase deficient leukemia cells. AB - Murine L1210 and human HL-60 leukemia cells grown for 5-7 days in medium containing 1% serum without selenium supplementation [Se(-) cells] were severely depressed in selenoperoxidase (SePX) activity relative to selenium-supplemented controls [Se(+) cells]. Catalase (CAT) activity in Se(-) cells was unaffected up to this point, but thereafter began to increase. Two manifestations of this increase have been differentiated for both cell lines: (a) short-term induction of CAT (up to approx. twofold) after 2-3 weeks, followed by (b) long-term selection for cells that irreversibly express much higher levels of CAT, e.g., > 100 times (L1210) and > 10 times (HL-60) the levels observed in Se(+) controls after approximately 20 weeks. Although superoxide dismutase, glutathione S transferase, and glucose-6-P dehydrogenase activities were unchanged in Se(-) cells, GSH levels were elevated by 50-100%; like short-term CAT elevation, this could be reversed by supplying Se. Short-term Se(-) cells were more sensitive to H2O2-induced killing than Se(+) cells, evidently because SePX activity was important for peroxide detoxification. However, long-term Se(-) cells were markedly more resistant to H2O2 than Se(+) counterparts, consistent with the much higher levels of CAT in the former. Southern blot analysis revealed that the copy number of CAT DNA in a clone of long-term Se(-) L1210 cells was four- to fivefold greater than that in an Se(+) clone. Northern blot analysis of RNA from the same Se(-) clone showed a CAT mRNA level that was at least 40 times higher than that of the Se(+) control. Similar trends were observed for HL-60 cells. These results suggest that elevated CAT during long-term Se deprivation is a reflection of amplification and greater transcription of the CAT gene. PMID- 7872807 TI - Enhanced induction of the mitochondrial permeability transition following acute menadione administration. AB - Induction of the mitochondrial permeability transition in vitro is well characterized and widely implicated in the mechanism of oxidant-induced cell death. Despite an abundance of in vitro evidence, implication of mitochondrial dysfunction in the mechanism of chemical toxicity in vivo awaits demonstration of the induction of the mitochondrial permeability transition in tissues from intoxicated animals. Menadione (2-methyl-1,4-naphthoquinone), an agent known to induce the permeability transition in isolated liver mitochondrial in vitro, was administered as a single bolus to adult male rats, and hepatic mitochondria were isolated 24 h later. Mitochondria from menadione-treated rats exhibited an increased sensitivity to calcium-induced inhibition of state 3 respiration and loss of respiratory control, as well as a greater sensitivity to calcium-induced calcium release that was inhibited by cyclosporine A. Associated with this was the depolarization of membrane potential and swelling of mitochondria from menadione-treated animals, but not control animals. Both the calcium-dependent depolarization and swelling of mitochondria from menadione-treated rats were inhibited by adding either cyclosporine A or ruthenium red. The results are consistent with the induction of the mitochondrial permeability transition and provide the first evidence for the manifestation of an increased sensitivity to this response as a result of chemical exposure in vivo. PMID- 7872808 TI - Characterization of the glycosaminoglycan-binding region of lactoferrin. AB - Lactoferrin is a prominent component of neutrophil secondary granules and its blood concentration is increased in certain inflammatory diseases. Although the biochemical characterization of lactoferrin as an iron-binding protein has been well described, its physiological role in inflammation remains undefined. We examined the ability of lactoferrin to regulate glycosaminoglycan-accelerated thrombin-serine protease inhibitor (serpin) reactions. Lactoferrin effectively reduced the rate of thrombin-serpin (antithrombin and heparin cofactor II) reactions by three physiological glycosamino-glycans including heparin, heparan sulfate, and dermatan sulfate. An enzyme kinetics analysis showed that lactoferrin did not alter the apparent heparin-thrombin or the heparin antithrombin dissociation constant values for the heparin-catalyzed thrombin antithrombin reaction. However, the maximum reaction velocity at saturation with respect to either protein was markedly decreased by lactoferrin. The glycosaminoglycan-binding region of lactoferrin was analyzed following limited proteolysis using Staphylococcus aureus V8 protease. Two lactoferrin fragments with Mr's of approximately 8 and approximately 11 kDa were purified based on their affinity to heparin-Sepharose. Amino acid sequence analysis demonstrated that both peptides were from the N-terminus. Although slightly less capable compared to intact lactoferrin, the lactoferrin peptides effectively neutralized heparin, heparan sulfate, and dermatan sulfate-catalyzed serpin-thrombin inhibition reactions. In addition, lactoferrin N-terminal peptides have approximately the same binding affinity to heparin-Sepharose as that of intact lactoferrin. Inspection of both the N-terminal amino acid sequence and the crystal structure of lactoferrin further supports the conclusion that lactoferrin is a novel glycosaminoglycan binding protein and that the putative glycosaminoglycan-binding site is localized to the N-terminus. PMID- 7872809 TI - The inactivation of bifunctional peptidylglycine alpha-amidating enzyme by benzylhydrazine: evidence that the two enzyme-bound copper atoms are nonequivalent. AB - Peptidylglycine alpha-amidating enzyme catalyzes the two-step conversion of C terminal glycine-extended peptides to C-terminal alpha-amidated peptides and glyoxylate in a reaction that requires O2, ascorbate and 2 mol of copper per mole of enzyme [Kulathila et al. (1994) Arch. Biochem. Biophys. 311, 191-195]. Peptides with a C-terminal alpha-hydroxyglycine residue are intermediates in the amidation reaction. Benzylhydrazine inactivates the enzymatic conversion of dansyl-Tyr-Val-Gly to dansyl-Tyr-Val-NH2 in a time- and concentration-dependent manner. In contrast, the enzymatic conversion of dansyl-Tyr-Val-alpha hydroxyglycine to dansyl-Tyr-Val-NH2 is unaffected by benzylhydrazine. The plot of 1/(inactivation rate) vs 1/[benzylhydrazine] is parabolic, indicating that the inactivation results from the interaction of 2 mol of benzylhydrazine per mole of enzyme. EPR spectra obtained from benzylhydrazine inactivation reactions carried out in the presence of a radical trap, alpha-(4-pyridyl-1-oxide)-N-tert butylnitrone, show the formation of a carbon-centered benzyl radical. The benzyl radical most likely results from redox chemistry between benzylhydrazine and the enzyme-bound Cu(II) ions because EPR studies show that enzyme-bound Cu(II) is reduced to Cu(I) in the presence of benzylhydrazine. The kinetic constants for benzylhydrazine as a reductant in the amidation reaction were determined at benzylhydrazine concentrations too low to cause significant enzyme inactivation. Mimosine exhibits mixed inhibition vs benzylhydrazine; however, previous results have shown that benzylhydrazine is competitive vs ascorbate [Miller et al. (1992) Arch. Biochem. Biophys. 298, 380-388]. This change in kinetic mechanism coupled with the nonlinear inactivation kinetics have lead to a proposal that the two enzyme-bound Cu(II) atoms are nonequivalent with respect to their reduction by benzylhydrazine. PMID- 7872811 TI - [Macroscopic study of specimens resected from breasts]. PMID- 7872810 TI - [Epidemiology of cancer of the breast]. AB - Breast cancer is a major public health problem. In 1980, breast cancer represented 18% of all cancers in women throughout the world. The worldwide incidence of breast cancer is increasing by 1.5% per annum and is influenced by geographical factors and by age. In France, this disease represents 19% of cancer deaths in women and is the commonest cause of cancer death in women. Several risk factors have been suspected, but many points remain obscure. The age of the menarche, the age of menopause, parity and the age of the first pregnancy influence the incidence of breast cancer. The use of oral contraceptives and hormone replacement therapy for menopause do not appear to affect the development of malignant breast disease, except, perhaps, in certain subgroups of patients, but this remains to be confirmed. The risk is increased by a fatty diet and by excessive alcohol consumption. It is now generally accepted that a family history of breast cancer is associated with an increased risk. In the future, a more precise understanding of genetic anomalies related to cancer will allow early diagnosis, particularly of familial forms. Many unresolved aspects of the risk factors of breast cancer could be elucidated by cohort studies. PMID- 7872812 TI - [Anatomopathological problems of mastopathies at risk]. AB - As breast cancer screening programmes gain momentum, there is a parallel increase in histological problems mainly related to the identification of an increasing number of "borderline" breast lesions. The results of recent studies are often inconsistent, and bear witness to the lack of a consensus regarding the interpretation of both ductal and lobular epithelial hyperplasia. The authors insist on the need for an adequate number of samples and an irreproachable histologic technique which is indispensible if the morphologic subtleties, currently the only valid factors permitting the diagnosis, are to be appraised. The role of the pathologist is therefore crucial in the management of specimens which are entrusted to him and in helping the clinician to tailor treatment to fit each individual patient. PMID- 7872813 TI - [Cytopuncture of the breast. How deep? From palpable to impalpable. From diagnosis to prognosis]. PMID- 7872814 TI - [Impalpable cancers of the breast. Histological and immunohistochemical study]. AB - Breast cancer screening enables the diagnosis of impalpable lesions detectable by mammography or ultrasonography. The diagnosis of impalpable cancers lacking macroscopic disorders is difficult. However the diagnosis is facilitated by X raying of surgical specimens, which shows that screened breast lesions have effectively been excised and which exactly localize these lesions. In addition, the X-raying of sliced (5 mm thick) fresh surgical specimens during surgery, enables the intraoperative diagnosis on frozen section of 72% of breast carcinomas and a one step surgical treatment (clear specimen edges, axillary lymph node excision). Moreover, the intraoperative examination of surgical specimens enables appropriate sampling of tissue for delayed immunodetections on frozen sections. These immunodetections provide prognostic information complementary to current microscopic investigation, particularly relevant in small node negative tumors. PMID- 7872815 TI - [Carcinoma in situ. Prognostic factors]. PMID- 7872816 TI - [Intra-tissue biological markers in cancers of the breast: current assessment]. AB - Among the great many prognostic factors currently available in breast cancer, three classes of tissue biological parameters appear to be the most reliable in the establishment of a clinical decision flowchart, when they will have been technically and clinically validated: parameters of hormone dependence, tumour aggressiveness and invasion and parameters of proliferation. This article discusses the difficulties encountered in the evaluation of some of these parameters (hormone receptors by various methodological approaches, proteases, enzymes involved in cell proliferation), with emphasis on standardisation of techniques, development of quality controls, clinical validation and objective information of the medical and scientific communities. PMID- 7872817 TI - [Biological prognostic factors of cancers of the breast and their consequences on the therapeutic choice]. AB - The value of prognostic factors can be measured by their influence on the therapeutic decision. Today, with the exception of clinical stage (TNM classification) and to a certain extent estrogen receptors, prognostic factors have little or no application in the clinical practice. The great number of parameters and the discrepancies between various studies may provide some explanations. By the study of the genetic evolution of breast cancers at the chromosomal level, we propose an approach to the understanding of the redundancy of prognostic factors, often noted by the authors. The consequences on the multiparametric statistical methodology are also discussed. Finally, by distinguishing between prognostic factors (predicting survival) and predictive factors (related to treatment response), we hope to provide indications for a better use of the progress in our knowledge on the biology of breast cancers. PMID- 7872818 TI - President's message: in health care reform, the focus is clearly on customers. PMID- 7872819 TI - ANNA seeks to collaborate with renal community on guidelines. PMID- 7872820 TI - Nursing interventions for rehabilitating renal patients. AB - Of the more than 180,000 Americans who have end stage renal disease (ESRD), only 25% of those of working age (18-55) are employed. This figure has remained low despite improvements in technology and pharmacology. In 1993, a Life Options Rehabilitation Advisory Council identified five areas that must be targeted to achieve rehabilitation success: employment, exercise, education, encouragement and evaluation (the 5 E's). This article addresses nursing interventions for rehabilitation related to these five E's. PMID- 7872821 TI - Patient education: renal osteodystrophy and adequacy of dialysis. AB - At The Kidney Center of Delaware County in Southeastern Pennsylvania, tools were developed that address adequacy of dialysis and renal osteodystrophy. Team members use the tools to provide quality care and education of patients. In this article, the tools, their use, and their benefits, are discussed. PMID- 7872822 TI - Rehabilitation experiences of patients receiving dialysis. AB - The concept of "rehabilitation" contains physical, psychosocial, and vocational elements. An exploratory study was developed by ESRD Network 18 regarding patient rehabilitation experiences in Southern California. A questionnaire was developed, and data collected from 248 randomly selected work-eligible ESRD patients in the network. Results showed relatively few significant differences between employed and unemployed ESRD patients in terms of demographics, and on many aspects of physical function, psychosocial adaptation, and vocational rehabilitation potential. However, unemployed patients reported lower energy levels, less stamina for working, greater benefits for not working, and problems with vocational rehabilitation programs. Unemployed patients also had more negative attitudes about achieving life goals and former job experiences. To help patients overcome barriers to rehabilitation, facility staff can focus on management of ESRD complications, assisting patients with support groups, connecting patients to rehabilitation resources early, and encouraging employed patients to continue working as long as possible. PMID- 7872823 TI - Participatory control in chronic hospital-based hemodialysis patients. AB - The purpose of this study was to determine chronic hospital-based hemodialysis patients' perceptions of control over selected aspects of hemodialysis care and to compare the patients' ratings with the global ratings of nurses caring for them. Two versions of a 14-item Hemodialysis Control Questionnaire (HCQ) were developed, one for patients (HCQ-P) and one for nurses (HCQ-N). Forty-seven patients and 32 nurses rated both perceived and desired control for each aspect of hemodialysis care on the HCQ. Reasons for their ratings were elicited and recorded. High test-retest reliability was established for both perceived and desired control on the HCQ-P and the desired control component of the HCQ-N. Patients rated their overall perceived and desired control as moderate, likewise the nurses' global score for desired control was rated as moderate. Item-by-item analysis revealed that nurses overestimated the patients' desired control over technical aspects of care but underestimated the patients' desire for more control over nontechnical aspects of care. The content analysis of the verbatim responses supported the quantitative findings. PMID- 7872824 TI - Case study of the anemic patient: epoetin alfa--focus on protocols. AB - The complex task of managing the anemia caused by end-stage renal disease (ESRD) is more easily accomplished when the patient care team uses a protocol as a guide. The protocol outline presented in this article facilitates the management of patients with ESRD who are receiving Epoetin alfa. A case study is used to illustrate the clinical application of the protocol. PMID- 7872825 TI - Pregnancy complicated by acute renal failure requiring hemodialysis. AB - The goal of a successful, full-term vaginal birth of a healthy infant was achieved while avoiding acidosis, hyperkalemia, and fluid overload in this pregnant patient with ARF. Acting in a prudent manner to prevent potential life threatening complications was of paramount importance in this patient whose etiology of renal failure was uncertain. In the case of the pregnant patient, an ultrasound may not be as valuable a diagnostic tool when the enlarged gravid uterus cannot allow complete visualization of the ureters. Interdepartmental collaboration in the case of this challenging patient resulted in a mutual learning experience, while ensuring a safe delivery for both mother and child. Additionally, by working together, the professional staff enhanced the patient's ability to meet the expected outcomes. PMID- 7872826 TI - Decreasing exit site infections with co-trimoxazole therapy. PMID- 7872827 TI - New trends in aminoglycoside dosing. AB - Aminoglycosides are narrow spectrum antibiotics used primarily for serious aerobic gram-negative infections. The concept of once daily dosing to reduce aminoglycoside toxicity while ensuring adequate serum concentrations has many advantages. The properties of PAE and concentration dependent bactericidal activity are especially valuable. Comparison of single daily dosing to traditional thrice daily dosing has proven to be of equal efficacy in clinical trials. In addition to the projected reduction of ototoxicity and nephrotoxicity, once daily dosing would guarantee peak serum concentrations in the therapeutic range, provide easier outpatient administration, decrease personnel time, and reduce costs. PMID- 7872828 TI - A metabolic unit for studies on human nutrition. AB - In clinical nutrition we are used to dealing with the clinical management of patients, but of equal or greater importance is the study of how nutrition affects the development of diseases or modifies its manifestations. This field is complex and links physiological studies of nutrition to the epidemiological analyses which form the basis of thinking in public health in Mexico today. Thus a number of studies have investigated the nutritional risk factors leading to the development of diseases such as heart disease and cancer (1-10). This epidemiological research requires the difficult task of accurately assessing the food consumption of individuals: with poor methodologies the chances of erroneous results are very high. This has implications for both group and individual comparison. Physiological studies on the effects of highly controlled changes in food intake on risk factors then allows the epidemiology to be interpreted in metabolic terms. In this paper we illustrate some of the benefits of metabolic studies and some of the requirements for this successful conduct. PMID- 7872829 TI - [Minimal time for detecting protein quality using indicators of protein catabolism in chickens]. AB - Previous studies shown that in chickens the hepatic activities of the purine enzymes Xanthine Dehydrogenase and Nucleoside Phosphorylase and the uric acid excretion can predict the quality of the protein consumed in a very short time. In these studies even though the experimental time was short, the time used for the conditioning of the chickens was long and included five days with six chickens per cage and then five to six days for progressively changing the chickens to individual cages in order to avoid the stress associated with the isolation of the animals. Thus the purpose of this study was to determine the minimal time required to detect differences in these parameters after feeding a soy-met and a gelatin diet and eliminating completely the time required for the isolation of the chickens. Thus, 76 one day old Warren male chickens were placed in groups of six on a soy-met powdered diet during five days and on day six all the chicken were placed in individual cages and one halve was offered the same diet while the rest received a gelatin diet. Then on day 1, 2, 3, 5, 7, 10 and 15 after the diet change five chickens on each diet were sacrificed and the activity of the liver purine enzymes as well as the uric acid excreted were determined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872830 TI - Effects of bermuda grass (Cynodon dactylon cv. Coast cross) and rice hulls on growth performance of 30 day-old weaned rabbits. AB - Several studies have demonstrated that rabbits can be maintained on diets containing high levels of Crude Fiber (CF) when compared to other monogastric animals. In the present study, we examined the effects of rice hulls and of bermuda grass (cv. Coast cross) on the growing performance of 30 day-old weaned rabbits. Rabbits were fed one of 5 diets containing rice hulls and/or bermuda grass as fiber source at the following proportions (BG/RH) 0/17.5, 15/11, 0/29, 14.7/19.1 and 48.5/0 for diets A, B, C, D and E, respectively. Body weight gain and voluntary feed intake were measured at 30, 44, 58 and 72 days. The time necessary to attain 2 kg of live body weight was not affected by the diets. However, daily weight gain differed significantly during the first two weeks after weaning among dietary groups. Diets C and D caused a lower body weight gain, probably because of the high level of Acid Detergent Fiber (ADF) in the diet (24% and 23%). Voluntary feed intake increased with age in all treatments, but food intake was lower in treatments C and D when compared to animals receiving treatments B and E. The present results demonstrate that when rice hulls are used as fiber source, fiber must be given as ADF and not as CF because the difference between ADF and CF is enormous. Rice hull-containing diets balanced with CF give an inappropriate amount of components that seem to affect the growth performance of young animals. PMID- 7872831 TI - The tortilla making properties of two improved maicillo cultivars from Honduras. AB - Grains of two improved maicillo hybrids (Sorghum bicolor (L) Moench) and their criollo (Landrace) counterparts grown at two farmsites in Honduras were lime cooked and processed into table tortillas. Kernels from the criollos were less dense and softer than kernels from the improved cultivars. The improved maicillos had straw or red plant and glume colors while the criollos were less dense and softer than kernels from the improved cultivars. The improved maicillos had straw or red plant and glume colors while the criollos had purple colored plants with black or purple glumes. The soft textured criollo kernels required less cooking than their harder improved counterparts. Nixtamals cooked to contain 53-55% moisture were the most suitable for processing into tortillas. Both improved maicillos compared favorably with Sureno (used as positive control during processing). The criollos produced darker, less acceptable tortillas. Masa and tortillas from criollos darkened during lime-cooking especially during baking. All sorghums and their respective tortillas had similar chemical composition. The improved maicillos bred in Honduras have a significantly improved plant and glume color with white pericarp. The sorghum improvement was also observed in the overall tortilla quality. PMID- 7872832 TI - [Nutritional evaluation of sweet potato cultivars Ipomea batata (L.) Lam used in bread as partial substitute of wheat flour]. AB - Four hundred and forty entries of sweet potato tubers from the International Potato Center were evaluated for chemical characteristics related to nutritional value. Dry matter range in the group was 15 to 45g/100g. The native entries DLP 2393, DLP 1120, DLP 2312, DLP 1908 and the foreign RCB 361F were selected for use in bread manufacture. Their average dry matter and crude protein was 38.5 and 9.2% respectively. Sweet potato bread was made replacing 30% of wheat flour with grinded sweet potato tubers. This bread had 11.0% crude protein in dry matter basis which were the same for bread made of wheat flour. There were no differences in organoleptic characteristics or protein quality (Apparent biological value: 37 vs 42%; apparent digestibility: 81 vs 80%; net protein utilization: 33 vs 39%) between sweet potato or full wheat flour breads respectively. PMID- 7872833 TI - [Elaboration of instant corn flour by hydrothermal process I]. AB - The objective of this research was to investigate a simplified hydrothermal process for the production of instant corn flour and evaluate some variables that affected the degree of gelatinization of corn flour, and evaluate some technological characteristics of the flour. The use of grits of lesser particle diameter and increasing temperature of the soaking water resulted in an increase in the rate of absorption of water of grits, permitting a reduction of soaking time necessary for the process. The instant corn flour prepared by the hydrothermal process using corn grits soaked in water at room temperature (28-30 degrees C) for 5 hours and steaming for 1 minute at 118 degrees C presented characteristics of viscosity, water absorption index and water solubility index similar to that of flours prepared with grits soaked in water at a temperature higher tan room temperature and different steaming time (5 and 15 minutes). The characteristics of color and shelf life of corn flour were improved with the hydrothermal process. PMID- 7872834 TI - [Chemical characteristics and uses of instant corn flour II]. AB - The hydrothermal process using corn grits soaked in water at room temperature (28 30 degrees C) for 5 hours and steaming for 1 minute at 118 degrees C did not affect the proximal composition of the corn flour. However, the amino acid content was reduced approximately 18% (specially lysine and tryptophan). Vitamin and pigment contents were few affected. The characteristics of color and shelf life of corn flour were improved with the hydrothermal process. Tortillas prepared with instant corn flour showed better color and texture in comparison to the tortillas prepared by the conventional process. Polentas prepared with instant corn flour with 30 seconds of mixing showed better characteristics of flavor, odor, texture and required less preparation time than commercial polentas. PMID- 7872835 TI - [Effect of addition of instant corn flour on rheological characteristics of wheat flour and breadmaking III]. AB - The instant corn flour prepared by the hydrothermal process using corn grits soaked in water at room temperature (28-30 degrees C) for 5 hours and steaming for 1 minute at 118 degrees C presented characteristics similar to that of flours prepared with grits soaked in water at temperature higher than room temperature and different steaming time (5 and 15 minutes). The addition of instant corn flour up of a 25% mixture with wheat flour reduced the peak of maximum viscosity during the heating cycle; however, the final viscosity during the cooling cycle was increased. The water absorption was increased with the increase of substitution in the level of wheat flour. Extensibility, maximum resistance and values of area were reduced with an increase in the level of instant corn flour in the mixture. However, extension resistance and proportional number were increased. Bread prepared from a mixture of instant corn flour and wheat flour showed higher weight with low loaf volume, color and texture of the crumb related to bread wheat. PMID- 7872836 TI - Localization of the sapA gene on a physical map of Campylobacter fetus chromosomal DNA. AB - We constructed a physical map of Campylobacter fetus TK(+) chromosomal DNA digested by either SmaI, SalI, or NotI using pulsed-field gel electrophoresis and Southern hybridization data. The genome size of C. fetus TK(+) is 2016kb, larger than that reported by the others. To locate the sapA gene, which encodes the surface array protein (SAP), on the physical map, we performed Southern hybridizations with probes based on the conserved region of the sapA gene. The results showed that more than seven copies of the conserved region were present on C. fetus chromosomal DNA and that the sapA gene was located on a limited number of fragments forming a cluster of genes. By comparing fingerprint patterns of strain TK(+) and strain TK(-), which lost the ability to produce SAP during culture on agar medium, an approximately 10kb deletion was observed in the fragments of strain TK(-). The results of Southern hybridization with two probes, one from the upstream region and the other from the variable region of sapA, suggest that the loss of SAP expression might not be the result of the loss of the sapA gene itself, but only a loss of its control systems. PMID- 7872837 TI - Glucose-induced inactivation of isocitrate lyase in Aspergillus nidulans. AB - The existence of a second mechanism of catabolite control of isocitrate lyase of Aspergillus nidulans, in addition to the carbon catabolite repression phenomenon recently reported was analysed. Isocitrate lyase was rapidly and specifically inactivated by glucose. The inactivation was irreversible at all stages in the presence of cycloheximide, showing that reactivation depends on de novo protein synthesis. In addition, analysis of glucose-induced inactivation of isocitrate lyase in a creAd-30 strain showed that the creA gene is not involved in this process. PMID- 7872838 TI - The role of regulatory genes nifA, vnfA, anfA, nfrX, ntrC, and rpoN in expression of genes encoding the three nitrogenases of Azotobacter vinelandii. AB - Several regulatory gene mutants of Azotobacter vinelandii were tested for ability to synthesize functional nitrogenase-1 (Nif phenotype), nitrogenase-2 (Vnf), or nitrogenase-3 (Anf). While nifA mutants were Nif-, Vnf+, and Anf+/-, and ntrC mutants were Nif+, Vnf+, and Anf+, nifA ntrC double mutants were Nif-, Vnf-, and Anf-. A vnfA mutant was Nif+, Vnf+/-, and Anf+/-, and an anfA strain was Nif+, Vnf+, and Anf-. lacZ fusions in the nifH, vnfH, vnfD, anfH, and nifM genes of Azotobacter vinelandii were constructed and introduced into wild-type and regulatory mutants of A. vinelandii. Expression of these operons correlated with the growth phenotype of the regulatory mutants. Apparently either NifA or NtrC can activate expression of nifM. Also, expression of the anf operon required the NifA transcriptional activator, although there are no NifA binding sites at appropriate locations upstream of anfH (or anfA). The results confirm previous reports that VnfA and AnfA are required for expression of vnf and anf genes, respectively, and that VnfA is involved in repression of the nifHDK operon in the absence of molybdenum and of the anfHDGK operon in the presence of vanadium. PMID- 7872839 TI - A novel pathway of peptide biosynthesis found in methanogenic Archaea. AB - The peptide subunits of the pseudomurein, the cell-wall peptidoglycan of some methanogens, are usually composed of glutamic acid, alanine and lysine. In order to get a more detailed picture of the biosynthetic pathway of the peptide subunit, we performed in vitro assays. Starting from glutamic acid a pentapeptide was obtained in seven steps: [formula: see text] The pentapeptide structure was identical to that of the peptide subunit of the intact pseudomurein except one additional alanine residue, which is split off during further processing. The pentapeptide synthesis starts with glutamic acid, which is phosphorylated at the N alpha-amino group. N alpha-phosphoryl-glutamic acid is transferred to a nucleotide-carrier, forming N alpha-UDP-glutamic acid. The further pentapeptide biosynthesis is achieved via a di-, tri- and tetrapeptide by stepwise addition of the corresponding amino acids. PMID- 7872841 TI - Neuroleptic withdrawal in schizophrenic patients. A review of the literature. PMID- 7872840 TI - Extracellular arabinases in Aspergillus nidulans: the effect of different cre mutations on enzyme levels. AB - The regulation of the syntheses of two arabinan-degrading extracellular enzymes and several intracellular L-arabinose catabolic enzymes was examined in wild-type and carbon catabolite derepressed mutants of Aspergillus nidulans. alpha-L Arabinofuranosidase B, endoarabinase, L-arabinose reductase, L-arabitol dehydrogenase, xylitol dehydrogenase, and L-xylulose reductase were all inducible to varying degrees by L-arabinose and L-arabitol and subject to carbon catabolite repression by D-glucose. With the exception of L-xylulose reductase, all were clearly under the control of creA, a negative-acting wide domain regulatory gene mediating carbon catabolite repression. Measurements of intracellular enzyme activities and of intracellular concentrations of arabitol and xylitol in mycelia grown on D-glucose in the presence of inducer indicated that carbon catabolite repression diminishes, but does not prevent uptake of inducer. Mutations in creA resulted in an apparently, in some instances very marked, elevated inducibility, perhaps reflecting an element of "self" catabolite repression by the inducing substrate. creA mutations also resulted in carbon catabolite derepression to varying degrees. The regulatory effects of a mutation in creB and in creC, two genes whose roles are unclear, but likely to be indirect, were, when observable, more modest. As with previous data showing the effect of creA mutations on structural gene expression, there were striking instances of phenotypic variation amongst creA mutant alleles and this variation followed no discernible pattern, i.e. it was non-hierarchical. This further supports molecular data obtained elsewhere, indicating a direct role for creA in regulating structural gene expression, and extends the range of activities under creA control. PMID- 7872843 TI - Why neuroleptic withdrawal in schizophrenia? PMID- 7872842 TI - Neuroleptic withdrawal in schizophrenic patients. PMID- 7872845 TI - Neuroleptic withdrawal in schizophrenic patients. An idea whose time has come. PMID- 7872844 TI - Long-term treatment for lifetime disorders? PMID- 7872846 TI - The early course of schizophrenia and long-term maintenance neuroleptic therapy. PMID- 7872847 TI - Risks of withdrawing antipsychotic medications. PMID- 7872848 TI - Considering neuroleptic maintenance and taper on a continuum. Need for individual rather than dogmatic approach. PMID- 7872849 TI - Adrenal gland volume in major depression. Increase during the depressive episode and decrease with successful treatment. AB - BACKGROUND: Hyperactivity of the pituitary-adrenocortical axis is the most prominent neuroendocrine abnormality in major depression. It is state-related, returning to normal with resolution of the depressive episode. Adrenal gland enlargement also has been reported in patients with major depression and has been hypothesized as an index of cumulative lifetime depression. However, whether or not adrenal enlargement decreases with successful treatment of depression has not yet been studied, to our knowledge. We, therefore, determined adrenal gland volume in patients with major depression before and after treatment and in matched normal controls, and compared adrenal size with functional indexes of pituitary-adrenocortical activity. METHODS: Adrenal volumes were measured by magnetic resonance imaging in nine adult and two adolescent patients with major depression during their illness and during full remission when medication had been stopped for at least 1 month, and in nine adult and two adolescent normal control subjects individually matched to the patients. Basal, 4 to 7 PM plasma corticotropin 1-39 and cortisol levels, and corticotropin 1-39 and cortisol responses to administration of ovine corticorelin and lowdose cosyntropin also were measured. RESULTS: Mean adrenal gland volume was significantly larger, by about 70% in the patients while depressed than after successful treatment, and it also was significantly larger, again by about 70%, than the mean adrenal gland volume of their matched controls. After treatment, the mean adrenal volume of the patients decreased and was no longer significantly different from that of their controls at baseline. The magnitude of the decrease was significantly positively correlated with the duration of the depressive episode. Basal, late-afternoon plasma corticotropin 1-39 levels were significantly lower in the patients while depressed than in their matched controls, but basal plasma cortisol levels did not differ significantly among the three groups, nor did the corticotropin 1-39 and cortisol responses to corticorelin or the cortisol response to cosyntropin. Correlations between adrenal gland volume and basal corticotropin and cortisol levels, and the corticotropin and cortisol responses to hormone challenge, were not consistently in the expected direction in any of the three groups of subjects. CONCLUSIONS: Adrenal gland enlargement occurring during an episode of major depression appears to be state-dependent, in that it reverts to the normal size range during remission after treatment. It thus does not appear to be an index of cumulative lifetime depression. The lack of a discernible relationship between adrenal volume and pituitary-adrenocortical activity remains to be explained and might be related to noncorticotropin influences on the adrenal gland, including other tropic hormones and/or neural mechanisms. PMID- 7872850 TI - Prevalence and correlates of drug use and dependence in the United States. Results from the National Comorbidity Survey. AB - OBJECTIVES: To analyze nationally representative data on the lifetime and 12 month prevalences of use of and dependence on illegal drugs (marijuana/hashish, cocaine/crack, heroin, hallucinogens), nonmedical prescription psychotropic drugs (sedatives, tranquilizers, stimulants, analgesics), and inhalants; and to examine data on the sociodemographic correlates of use and dependence. METHODS: The data come from the National Comorbidity Survey, a structured diagnostic interview administered to persons aged 15 to 54 years that generates reliable diagnoses according to the definitions and criteria of DSM-III-R. RESULTS: Of the respondents, 51.0% used one of the above drugs at some time in their lives, and 15.4% did so in the past 12 months. These estimates are similar to those obtained in the 1991 National Household Survey of Drug Abuse, where lifetime prevalence was 45.2% and 12-month prevalence was 16.7% among respondents in the age range 15 to 54 years. Of National Comorbidity Survey respondents, 7.5% (14.7% of lifetime users) were dependent at some time in their lives and 1.8% were dependent in the past 12 months. The prevalence estimate for lifetime dependence was reduced to 5.3% when calculated the percentage of respondents in the age range of 28 to 54 years who reported an onset of dependence as of 10 years earlier (ie, when they were 18 to 44 years old) was computed. This is similar to the Epidemiologic Catchment Area Study estimate of 5.1% among respondents in the age range 18 to 44 years, a comparison that matches the two studies on year of assessment, age of risk, and cohort. Males were significantly more likely to report both lifetime and 12-month use and dependence. Use and dependence were found to be more common in cohorts born after World War II than those born before the end of the war. The demographic predictors of lifetime use differed from the predictors of lifetime dependence among users, and these, in turn, differed from the predictors of recent dependence among people with a lifetime history of dependence. CONCLUSIONS: Drug use and dependence are highly prevalent in the general population. The fact that there are differences in the correlates of first use, dependence among users, and persistence of dependence means that future research aimed at pinpointing modifiable risk factors must be based on disaggregated analyses of separate stages of progression. PMID- 7872851 TI - Generalized social phobia. Reliability and validity. AB - OBJECTIVE: To investigate the reliability and validity of DSM-III-R "generalized" social phobia by examining interrater agreement and comparing patients with generalized and "nongeneralized" social phobia on demographic characteristics, clinical variables, and familial social phobia. DESIGN: Two senior clinicians classified 129 patients attending an anxiety clinic as having DSM-III-R social phobia that is generalized (fears most social situations) or nongeneralized (less than most) based on independent narrative review. RESULTS: Good reliability was achieved (kappa = 0.69). Patients with generalized social phobia were more often single, had earlier onsets of social phobia, had more interactional fears, and had higher rates of atypical depression and alcoholism. Familial social phobia was more common among patients with generalized social phobia than patients with nongeneralized social phobia and controls, with no difference between the latter two groups. CONCLUSIONS: Generalized social phobia (1) can be distinguished reliably from nongeneralized social phobia, (2) is a valid subtype, and (3) may characterize a familial form of the disorder. PMID- 7872852 TI - A trial of the effect of a standardized psychiatric consultation on health outcomes and costs in somatizing patients. AB - BACKGROUND: Patients who somatize but who do not meet criteria for somatization disorder are common in the community. Virtually no research has been conducted to determine how to treat these patients. METHODS: We conducted a randomized controlled clinical trial of a psychiatric consultation intervention we had previously shown to improve the management of somatization disorder. The study population included 51 physicians treating 56 somatizing patients who had a history of seeking help for six to 12 lifetime unexplained physical symptoms. At the onset of the experiment, physicians randomized to the treatment condition received a consultation letter recommending a specific management approach; physicians randomized to the control/crossover condition received the consultation letter after 12 months. Data on health outcomes and charges were collected every 4 months for 2 years after randomization for 96% of subjects who entered the study. RESULTS: Patients of physicians who received the intervention reported significantly increased physical functioning, an improvement that remained stable during the year after the intervention. The intervention reduced annual medical care charges by $289 (95% confidence interval, $40 to $464) in 1990 constant dollars, which equates to a 32.9% reduction in the annual median cost of their medical care. CONCLUSIONS: Somatizing patients with a lifetime history of six to 12 unexplained physical symptoms reported better physical functioning after their primary care physician was provided appropriate treatment recommendations via a psychiatric consultation. Such a consultation is cost effective because it reduces subsequent charges for medical care, while improving health outcomes in a chronically impaired population. PMID- 7872853 TI - Investigation of the conformational influences on the estrogenic activity of 1,2 bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamines and of their platinum(II) complexes, II: Synthesis and studies on the estrogenic activity of cis- and trans[bis(2,6-dichloro-4-hydroxybenzylamine)]dihaloplatinum(II)-c omplexes. AB - 2,6-Dichloro-4-hydroxybenzylamine (1) and its N-methyl (2) and N-ethyl (3) derivatives were synthesized and tested for estrogen receptor affinity as well as for estrogenic activity. In contrast to their related highly active 1,2-bis(2,6 dichloro-4-hydroxyphenyl)ethylenediamines (meso-4 - meso-6) none of the benzylamines showed hormonal activity. The coordination of the benzylamine 1 to platinum did not lead to an estrogenic compound. The reasons for the different activity of [meso- 1,2(bis-2,6-dichloro-4 hydroxyphenyl)ethylenediamine]dichloroplatinum(II ) (meso-4-PtCl2) and cis[bis(2,6-dichloro-4-hydroxybenzylamine)]dichloroplatinum(II) (cis-1-PtCl2), the latter of which can be considered as a ring-opened counterpart of the highly active meso-4-PtCl2, are thoroughly discussed under inclusion of conformational facts. The results of this and the preceding work show, that the pharmacophore meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine (meso-4) which is exclusively responsible for the estrogenic activity of meso-4-PtCl2 causes comparable hormonal effects in two different conformations with O-O distances of about 8 A (complex) and of about 12 A (diamine). Therefore, we discuss two binding sites for estrogens in their receptor. PMID- 7872854 TI - New NO-donors with antithrombotic and vasodilating activities, VIII: Benzothiazole-2(3H)-nitrosimines. AB - Thirty title compounds were prepared and tested for their antiplatelet activity in the Born-test. Five nitrosimines inhibit the aggregation induced by collagen in concentrations below 10 mumol/L halfmaximally. Four compounds were investigated in an in vivo thrombosis model. An inhibition of thrombosis between 29 and 53% was observed in mesenteric arterioles of rats 2 h after p.o. administration (60 mg/kg). The effect in venoles was less pronounced (10-22%). For one compound these effects could still be demonstrated 4 h after oral application. PMID- 7872855 TI - NSAI activity study of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives. AB - A series of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives endowed with anti-inflammatory and related pharmacological properties were submitted to a more extensive study to know their exact pharmacological profile and their possible side effects. The studied compounds possess a remarkable analgesic activity, devoid of central effects. They also show an interesting anti inflammatory profile evidenced by their effectiveness in different experimental models of inflammation. In addition, these compounds exhibit none or very little activity on CNS, scarce toxicity and low gastrointestinal aggressivity. PMID- 7872856 TI - [Isochromanylpencillins]. AB - (R/S)-Isochroman-1-carboxylic acid (1) is resolved to its enantiomers and as well as these reacted with 6-aminopenicillanic acid to the title compounds 2. The activity of the new penicillin-derivatives against gram positive and gram negative bacteria is compared with that of benzyl penicillin. PMID- 7872857 TI - [Synthesis of 6-benzylidene-2-(alpha,alpha-diphenyl-alpha-hydroxyacetyl)-thiazolo -(3,2-b)-s-triazol-5-ones as potential biologically active compounds]. PMID- 7872858 TI - Homosexual foot fetishism. AB - 262 respondents from an organization for homosexual foot fetishists provide information from a broader sample than clinical cases and allow examination of the effects of sexual preference on fetishism. Data show a wide range of feet/footwear objects to be arousing. Such interests were often associated with particular types of men, yet interests were subject to change over time. Fetishistic arousal rested on both sensual and symbolic aspects of the fetish. Symbolically, it was the theme of "masculinity" that made male feet/footwear arousing, showing parallels to "femininity" evoked by female feet/footwear for male heterosexual fetishists. For many of the respondents, fetishism did not seem to be a substitute for living persons. Respondents had intimate relationships and were able to incorporate their fetish interests into stable relationships and less intimate ones. Considerable involvement in sadomasochistic practices was also found as was involvement in the gay world. Finally, nothing about a fetishistic interest seemed to preclude the development of subcultural forms around the practice. PMID- 7872859 TI - Self-report assessment of female sexual function: psychometric evaluation of the Brief Index of Sexual Functioning for Women. AB - Previous self-report measures of female sexual function have been either overly restrictive or inappropriate for use in large-scale clinical trials. Accordingly, we have developed the Brief Index of Sexual Functioning for Women (BISF-W), a 22 item, self-report instrument for the assessment of current levels of female sexual functioning and satisfaction. The BISF-W was administered at monthly intervals to a standardization sample of 269 women, ages 20-73 years. A principal components analysis yielded a three-factor solution--interest/desire, sexual activity, and satisfaction--which accounted for 51.2% of the variance. Concurrent validity was demonstrated by means of a comparison with the Derogatis Sexual Function Inventory. In addition, the BISF-W was compared to the Brief Sexual Function Questionnaire, a similar self-report measure of sexual functioning for men. Major advantages of the BISF-W are its ease of administration and scoring, suitability for use in both clinical and nonclinical samples, and assessment of key dimensions of female sexuality. However, based on its moderate test-retest reliability and internal consistency, further development of the instrument is indicated. PMID- 7872860 TI - Variability in middle childhood play behavior: effects of gender, age, and family background. AB - Parent-report questionnaires for the assessment of gender-normative and gender atypical behavior in childhood offers researchers the opportunity to conduct large-scale screenings of community samples of boys and girls. One important aspect of childhood gender role behavior includes play. Although play behavior inventories have been used clinically for the identification of gender disturbed boys, recent community-based surveys of play behavior in both genders are lacking. The present postal questionnaire survey of parents of 688, 6- to 10-year old children (boys = 333, girls = 355) attending one public school district (74% of the eligible sample), clarifies how subject's age, family race/ethnicity, and socioeconomic status influence gender differences in play. Significant gender differences were detected for 63 of the 69 games. With but few exceptions, the magnitude of the gender differences in play remained relatively constant across middle childhood. Older boys and girls decreased their participation in activities numerically dominated by girls whereas the reverse was true for male dominated activities. Parents' educational level influenced play for only a minority of items. Finally, whereas race/ethnicity significantly predicted game/activity participation in approximately one half of the items, a consistent influence of this variable on gender-related play did not emerge. In spite of dramatic changes in women's roles in the U.S. society over the past three decades, gender differences in middle childhood play have remained strong. PMID- 7872861 TI - Instructional control of female sexual responding. AB - To examine whether women can suppress genital arousal under instructional control, 25 women were presented with three erotic films and instructions to "become as aroused as possible" (Arouse) or to "suppress arousal" (Suppress). Genital responding was assessed using the heated oxygen electrode which yields two measures of vaginal responding: oxygen perfusion and thermistor assessment of vasocongestion. 36 to 40% of the sample was able to demonstrate a substantial reduction in sexual responding under Suppress instructions (depending upon the measure used), based on externally derived criteria to determine suppression. Differences were noted in the patterns of responding between suppressors and nonsuppressors, on both the pO2 and heat measures. Examination of thought-listing data indicated that subjects were able to identify cognitive strategies they used to suppress responding. In particular, successful suppressors were more likely to report the use of 2+ cognitive strategies, whereas the nonsuppressors reported reliance on a single strategy. Results are discussed in light of current theories of emotional factors in sexual responding, with emphasis on clinical implications. Directions for future research in female sexuality are highlighted. PMID- 7872862 TI - Psychosexual dysfunction in Indian male patients: revisited after seven years. AB - Short-term (1 year) outcome of 66 male patients with psychosexual dysfunction was studied in the context of patients' sociodemographic and clinical characteristics. A combination of erectile dysfunction and premature ejaculation was the most common diagnosis. Long-term (7 years) outcome of this cohort was evaluated in relation to short-term outcome. Improvement in the short-term indicated favorable long-term outcome. Initial dropout was associated with chronic and continuous sexual dysfunctioning. PMID- 7872863 TI - The effect of ethanol intake on the development of hepatocellular carcinoma in HBsAg carriers. AB - To study the effect of alcohol intake on the latency period for the development of hepatocellular carcinoma in a country where this tumor occurs earlier in life than in Southeast of Asia, Europe or North America, 83 male patients with hepatocellular carcinoma aged over 30 years, in which the HBsAg status and ethanol intake were prospectively investigated, were analyzed with respect to age at the time of diagnosis. Only male patients were used because in Vitoria, State of Espirito Santo, the age at the time of diagnosis of hepatocellular carcinoma in females is significantly lower than in males. Only patients aged over 30 years were used because the tumor occurs in young people and children, in which habitual alcohol intake is not common. Forty-six patients with hepatocellular carcinoma HBsAg positive and 36 HBsAg negative were separated in alcohol abusers (daily ingestion above 80 g for a period of 10 years or more) or nonalcoholics. The occurrence of associated liver cirrhosis was determined for each group. For comparison of the average age of the four groups the Student t test and the Kruskall-Wallis test for two groups were used. The results showed that the average age of patients with hepatocellular carcinoma HBsAg positive with habitual alcohol intake was significantly lower than those without drinking habit (44.3 +/- 9.7 and 52.3 +/- 15.7 years; P = 0.011 and 0.028 respectively for Student t test and Kruskall-Wallis test). The average age of patients with hepatocellular carcinoma HBsAg (-) with or without habitual ethanol intake showed no significative differences (56.7 +/- 11.3 and 57.3 +/- 12.4 P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872864 TI - Comparison of the effects of sublingual isosorbide dinitrate and cardiomyotomy on esophageal emptying in patients with chagasic megaesophagus. AB - The effects of surgical cardiomyotomy and isosorbide dinitrate on esophageal emptying were compared in 18 patients with symptomatic chagasic megaesophagus. The esophageal emptying of a radiolabelled test meal was assessed three times in each patient by a scintigraphic technique, twice before and once 10-14 days after cardiomyotomy. Isosorbide dinitrate, 5 mg by the sublingual route 5 min before the meal, preceded one of the preoperative studies. Esophageal retention at the completion of the meal was significantly less (P < 0.01) after both isosorbide dinitrate and cardiomyotomy than after the preoperative study not preceded by any treatment. This difference persisted up to 10 minutes after the meal. The values measured in the isosorbide dinitrate-preceded study and after cardiomyotomy were not different (P > 0.10) even though esophageal retention at the completion of the meal was slightly less after cardiomyotomy than after isosorbide dinitrate. These results show that isosorbide dinitrate and cardiomyotomy cause similar enhancement of esophageal emptying in chagasic megaesophagus. PMID- 7872865 TI - [Acute pancreatitis: a clinically based classification]. AB - Acute pancreatitis is a protean disease characterized by wide clinical variation and many pathological alterations. This variability in presentation and clinical course has plagued the study and management of the disease. The lack of accepted definitions for acute pancreatitis and its complications has led to difficulties in devising a clinical classification system useful for case management. An attempt in this direction was made by a diverse group of 40 international authorities from six medical disciplines and 15 countries, joining a Symposium in Atlanta, Ga, in September 1992. From this meeting resulted a clinically based classification system for acute pancreatitis valuable to practicing clinicians and to specialists seeking to compare inter institutional data. PMID- 7872866 TI - [Gastric emptying of sucrose and maltose and levels of respective disaccharidases in the small intestinal mucosa of adult rats]. AB - The gastric emptying of sucrose and maltose solutions at different concentrations, with addition of phenol red (6 mg%) used as a marker, was studied in 144 Wistar male rats. The gastric retention was determined 15 minutes after the orogastric infusion of sucrose and maltose solutions at 2.5%, 5% and 10% and volume of 1 and 2 ml/100 g weight of the animal, making 1 use of 12 rats for each volume and concentration. The activities of lactase, sucrase and maltase were evaluated in other eight rat's small intestine. The results demonstrated a maltase/sucrase activity rate of 4:1. The gastric retentions of the maltose solution were significantly higher than sucrose solution at 10% and 5% concentration, either 1 and 2 ml/100 g weight. There were no differences between gastric retention at 2.5% concentration neither with 2 nor 1 ml/100 g weight. As an explanation of these results it is proposed that the faster gastric emptying of sucrose solution 10% and 5% in relation with the same concentrations of maltose is due to a probable saturation of sucrase, that when achieved, interrupts the regulation of gastric emptying, determined by the intestinal receptors. PMID- 7872867 TI - [Primary intrahepatic lithiasis: report of a case and review of the literature]. AB - Primary intrahepatic lithiasis is an entity defined by intrahepatic stones exclusively located in the IH ducts above the emergence of the common bile duct. The disease is classified in two types: Eastern type (stones formed primarily in intrahepatic ducts; frequent in Japan) and Western type (stones formed in the extrahepatic bile system, usually in gallbladder, which migrate up to the intra hepatic ducts). The mechanisms of lithogenesis in the entity are as yet not fully understood; multiple factors seem to operate synergistically: anatomical changes of the intrahepatic ducts, metabolic disorders, infections, idiopathic alteration. All these factors may facilitate biliary stasis leading ultimately to stone formation. We report on a case of and review the literature on primary intrahepatic lithiasis, which is a rare occurrence in the West and a disease of difficult surgical approach and high mortality. PMID- 7872868 TI - [Diagnostic limitations of the isolation of trophozoites of Giardia lamblia in duodenal aspirates]. AB - Examination of fecal specimens for detection of Giardia lamblia cysts is known to produce a high percentage of false negative results while it is generally believed that duodenal juice often contains trophozoites even when the stool examination is negative. The aim of this study was to compare the detection of trophozoites in duodenal aspirate with the findings of cysts in stool samples for the diagnosis of asymptomatic giardiasis. Forty five children with iron deficiency anemia (one to six years of age) were studied, 21 with giardiasis and 24 without giardiasis. For each subject, one to five stool samples were examined for cysts of Giardia lamblia employing the formol-ether concentration method. Duodenal juice from all children were examined for the presence of trophozoites of Giardia lamblia. Fecal excretion of cysts was demonstrated in 20 (95%) of the 21 patients with giardiasis; however, only nine (43%) exhibited the presence of trophozoites in their duodenal aspirates. In one child trophozoites were observed in the duodenal aspirate; but the parasitologic investigation was negative for cysts in the feces. All the children without giardiasis had at least three stool samples and duodenal aspirate negative for Giardia lamblia. In conclusion, fecal examination by formol ether concentration method exhibited a greater number of positive results than did the duodenal aspirate microscopy method in the diagnosis of giardiasis. PMID- 7872869 TI - [The role of the abdominal ultrasonography and percutaneous liver biopsy in the differential diagnosis of neonatal cholestasis]. AB - Neonatal cholestasis still presents a diagnostic challenge, both from the anatomic and etiologic point of view. Distinguishing intrahepatic from extrahepatic causes of cholestasis is of paramount importance since the latter may be treated by surgery but prognosis depends on the age at which operation is performed. Many tests have been proposed to help in differentiating these two entities, among which liver biopsy is the most frequently employed, and ultrasonography one of the most recently included. Our purpose is to present our experience with these two methods in the differential diagnosis of intra and extrahepatic causes of cholestasis. From January 1989 to July 1993, 35 patients with neonatal cholestasis were evaluated through a protocol which included liver biopsy and ultrasonography. The latter was performed after a 4 hour fast and was considered indicative of extrahepatic cholestasis when the gallbladder was not visualized, was hypoplastic or non-functioning, or if a cystic structure was seen at the extrahepatic biliary tree. Sensitivity, specificity, and accuracy were determined for these two tests. Seventeen patients were found to have extrahepatic cholestasis (all with biliary atresia) and 18 intrahepatic cholestasis, on the basis of clinical evolution or operative findings. Sensitivity was 100% for ultrasonography and 76% for liver biopsy in diagnosing extrahepatic cholestasis. Accuracy was 83% for ultrasonography and 86% for biopsy, rising to 96% when both tests were considered together. Based on these findings we strongly recommend ultrasonography with definite criteria as the initial investigation tool in the management of neonatal cholestasis, associated with liver biopsy. PMID- 7872870 TI - [XVI Brazilian Congress of Neurology]. PMID- 7872872 TI - High tech, low tech in the era of health reforms. PMID- 7872871 TI - Predictive marker for the development of cerebral toxoplasmosis in patients with human immunodeficiency virus type 1. PMID- 7872873 TI - Phenytoin and cerebellar atrophy. PMID- 7872874 TI - Transient unresponsiveness in the elderly: possible episodes of idiopathic recurring stupor. PMID- 7872875 TI - Cerebrospinal fluid homovanillic acid in the DATATOP study on Parkinson's disease. Parkinson Study Group. AB - OBJECTIVES: To determine whether cerebrospinal fluid (CSF) homovanillic acid (HVA) concentration in subjects with early, mild Parkinson's disease (PD) treated with the monoamine oxidase type B inhibitor selegiline hydrochloride differs from that of control subjects receiving placebo. Our hypothesis is that if selegiline offers neuroprotection in such patients, the HVA levels should not decrease over time as much as in those receiving placebo. A second objective was to define the kinetics of recovery of HVA concentration after discontinuation of selegiline therapy. DESIGN: During the controlled clinical trial DATATOP (deprenyl [selegiline] and tocopherol antioxidative therapy of parkinsonism) (which examined the effects of selegiline and tocopherol in 800 subjects with early, untreated PD), the CSF HVA concentration was measured at baseline and again 4 weeks after the study end point (need for levodopa therapy) was reached and medications were withdrawn (n = 265). Based on an interim analysis, the lumbar puncture protocol was modified, such that subjects who reached the study end point were randomly assigned an interval of 0 days or 2, 6, or 8 weeks between discontinuation of selegiline therapy and the lumbar puncture (n = 215). SETTING: In the hospital, after overnight bed rest and fasting. PATIENTS: The 800 subjects with early, mild PD who participated in the DATATOP controlled clinical trial. INTERVENTION: The four treatment arms were (1) selegiline-placebo and tocopherol placebo, (2) selegiline-placebo and active tocopherol (2000 IU/d), (3) active selegiline hydrochloride (10 mg/d) and tocopherol-placebo, and (4) active selegiline hydrochloride (10 mg/d) and active tocopherol (2000 IU/d). MAIN OUTCOME MEASURE: Cerebrospinal fluid HVA concentrations. RESULTS: The CSF HVA concentration at baseline did not correlate with disease duration or severity; the mean (+/- SD) HVA concentration was 34.7 +/- 17.0 ng/mL. In the 265 subjects who underwent analysis 4 weeks after the study end point was reached and medications were withdrawn, the decline in HVA concentration was significantly greater in subjects assigned to receive selegiline (9.2 +/- 12.7 ng/mL) than in subjects not receiving selegiline (3.2 +/- 14.4 ng/mL), indicating persistent monoamine oxidase (MAO) inhibition by selegiline. Tocopherol had no effect. Results from the modified protocol revealed that HVA concentration increased with time to approximately the same levels as determined in controls by 60 days but showed no clear final plateau level. At 0 days, HVA concentration was reduced from baseline by less than one third, indicating only partial inhibition of MAO activity by selegiline. CONCLUSIONS: Measurements of CSF HVA concentrations (1) indicate the long duration of MAO inhibition by selegiline, (2) have limited utility as a marker of severity or progression in PD, (3) indicate that selegiline does not provide sufficient MAO inhibition to test adequately the oxidative stress hypothesis of the cause of PD, and (4) lend no support for a protective role of selegiline in slowing the progression of PD. PMID- 7872876 TI - The risk of stroke in patients with first-ever retinal vs hemispheric transient ischemic attacks and high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial. AB - BACKGROUND: The prognosis of amaurosis fugax has been considered to be favorable compared with that of hemispheric transient ischemic attacks. However, this has remained uncertain for patients with significant carotid stenosis as the assessment of progression of the disease has been confounded when patients undergo carotid endarterectomy. In the North American Symptomatic Carotid Endarterectomy Trial, patients with high-grade (70% to 99%) carotid stenosis were randomized to receive either medical or surgical treatment, thus making an unconfounded analysis possible. METHOD: We identified 129 medically treated patients with high-grade carotid stenosis who had their first-ever transient ischemic attack as the entry event into the trial. Fifty-nine patients with retinal transient ischemic attacks (RTIAs) were compared with 70 patients with hemispheric transient ischemic attacks (HTIAs). RESULTS: Patients with HTIAs were older, with a higher prevalence of most risk factors for stroke. Average time of delay from the onset of transient ischemic attacks to medical treatment was longer for patients with RTIAs than for patients with HTIAs (48.5 vs 15.2 days). Kaplan-Meier estimates of the risk of ipsilateral stroke at 2 years were 16.6% +/ 5.6% for patients with RTIAs and 43.5% +/- 6.7% for patients with HTIAs (P = .002 for the difference in risk between RTIAs and HTIAs). From corresponding Cox's proportional hazards regression analyses, the risk of ipsilateral stroke ranged from 11.2% to 28.9% for patients with RTIAs and from 37.4% to 96.3% for patients with HTIAs across stenoses, spanning 75% to 95%. Overall, the relative risk of ipsilateral stroke (HTIAs compared with RTIAs) was 3.23 (95% confidence interval, 1.47 to 7.12), regardless of the degree of high-grade stenosis. CONCLUSION: To our knowledge, this study is the first report on the expected outcome for medically treated patients with high-grade (70% to 99%) carotid stenosis in whom the first-ever event was either an RTIA or HTIA. The presence of RTIAs carries a considerable risk of ipsilateral strokes, particularly at higher degrees of stenosis. However, in comparison with HTIAs, patients with RTIAs still have a better prognosis. PMID- 7872877 TI - Prediction of long-term outcome in the early hours following acute ischemic stroke. Italian Acute Stroke Study Group. AB - OBJECTIVE: To develop a model for predicting outcome in the first few hours after the onset of an ischemic stroke on the basis of the clinical findings obtained during a rapid bedside examination. DESIGN: Clinical records were retrieved from the data bank of a randomized multicenter trial. The resulting case series was split into two subgroups that served as a "training set" and a "test set." Logistic regression was applied to the training set to select the prognostic predictors among baseline clinical findings. The performances of the model based on independent prognostic predictors were then validated in the test set. SETTING: Eleven primary care institutions (either hospitals or university clinics) participating in the Italian Acute Stroke Study on the efficacy of hemodilution and monosialoganglioside in acute ischemic stroke. PATIENTS: Consecutive noncomatose patients (N = 300) observed within the first 6 hours after the onset of a first supratentorial ischemic stroke. MAIN OUTCOME MEASURE: Death or disablement 4 months after the index stroke. Disablement was defined as a score of 3 or higher on the Rankin Scale. RESULTS: Age and CNS score defined six risk groups with a predicted 4-month poor outcome rate ranging from 10% (patients aged 70 years or younger and with an initial CNS score of 7 or higher) to 89% (patients older than 70 years and with a CNS score of 4.5 or lower). When a risk of poor outcome of 60% was taken as a cutoff, the accuracy of the prediction was 78% +/- 6% in the training set and 72% +/- 9% in the test set. CONCLUSION: Long-term outcome can be predicted in the first few hours following an acute ischemic stroke by means of a simple model based on age and CNS score. PMID- 7872878 TI - Temporal lobe perfusion on single photon emission computed tomography predicts the rate of cognitive decline in Alzheimer's disease. AB - OBJECTIVE: To examine the ability of relative regional cerebral blood flow as measured by single photon emission computed tomography to predict longitudinal course of cognitive decline in Alzheimer's disease. DESIGN: Single photon emission computed tomography using the blood flow tracer 123I-N-isopropyl-p iodoamphetamine was performed at initial evaluation and was used to predict the rate of cognitive decline over a follow-up period from 1 to 4 years. SETTING: Outpatient university dementia clinic and center for functional imaging. PARTICIPANTS: Twenty-nine patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probably or possible AD. RESULTS: Temporal lobe regional cerebral blood flow ratio at initial evaluation correlated with rate of decline in Mini-Mental State Examination over the longitudinal follow-up. Temporal regional cerebral blood flow ratio also predicted rate of decline of specific memory measures on the California Verbal Learning Test. Neither parietal nor frontal ratios predicted rate of cognitive decline. Dorsolateral frontal hypoperfusion was associated with the emergence of perseverative behaviors over time. Age, prior dementia duration, estimated prior rate of decline, and initial severity did not predict rate of cognitive decline. CONCLUSION: Results suggest that regional perfusion on single photon emission computed tomography may predict cognitive decline in Alzheimer's disease better than these demographic and course variables. PMID- 7872879 TI - Peripherally induced tremor and parkinsonism. AB - OBJECTIVE: Trauma to the peripheral nervous system is a well-recognized cause of dystonia and tremor, but peripherally induced parkinsonism has not previously been documented. We seek to characterize peripherally induced tremor and parkinsonism and propose possible mechanisms for this phenomenon. DESIGN: Review of records of patients evaluated in the Movement Disorders Clinic between 1977 and 1993. In addition to demographic and clinical information, the records were screened for any potential predisposing factors. PATIENTS: Twenty-eight patients in whom the onset of tremor, parkinsonism, or both was anatomically and temporally related to local injury. INTERVENTION: The type and site of injury were verified by history and examination of records whenever possible. Severity of tremor and parkinsonism was assessed by clinical rating scales. Three patients with tremor and parkinsonism had their striatal [18F]-fluorodopa uptake and raclopride binding measured with positron emission tomography. MAIN OUTCOME MEASURE: Response to conventional antitremor and antiparkinsonian medication was assessed by a clinical rating scale. RESULTS: Severe local injury preceded the onset of movement disorder by 47.5 +/- 74.7 days (mean +/- SD). The mean age at onset of movement disorder was 46.5 +/- 14.1 years. Tremor was present in all 28 patients, 11 of whom exhibited additional parkinsonian features. In 20 patients, the movement disorder spread beyond the original site. Possible predisposing factors were identified in 13 patients; nine had essential tremor or a family history of essential tremor. In addition to tremor, dystonia and myoclonus were evident in 13 and three patients, respectively. Reflex sympathetic dystrophy was present in six patients. Tremor did not improve with medications, and only seven patients with parkinsonism responded to therapy with levodopa. CONCLUSION: Central reorganization in response to peripheral injury may give rise to a motor disturbance, including tremor and parkinsonism. PMID- 7872880 TI - Cerebral microembolism in patients with Sneddon's syndrome. AB - BACKGROUND: The pathogenesis of Sneddon's syndrome is unclear. This study addresses the question whether cerebral thromboembolism may be involved in the pathogenesis of the neurologic complications of the disorder. The study consisted of 13 patients with Sneddon's syndrome defined by both generalized livedo reticularis and a history of one or more cerebrovascular ischemic events; none had clinical or Doppler ultrasonographic evidence of atherosclerosis. METHODS: Transcranial Doppler microembolic monitoring of the middle cerebral artery; blood screening for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies). RESULTS: Five patients (38%) showed clinically silent microembolism at transcranial Doppler monitoring, with individual microembolic event rates of the middle cerebral artery between 2 per hour and 33 per hour. In this group, the time since the last ischemic symptom was significantly shorter than in the eight patients without microemboli. Antiphospholipid antibodies were detected in three patients (23%), all of whom belonged to the microemboli-positive group. CONCLUSIONS: These data suggest that the detectability of both clinically silent cerebral microembolism and antiphospholipid antibodies may provide paraclinical evidence of active disease in patients with Sneddon's syndrome. The results support the notion that an immune-mediated prothrombotic state facilitating the formation of arterial thrombi with subsequent cerebral embolization, and/or triggering in situ thrombosis of cerebral vessels, plays a pathogenetic role in the neurologic manifestations of this disorder. PMID- 7872881 TI - Exaggerated messenger RNA expression of inflammatory cytokines in human T-cell lymphotropic virus type I-associated myelopathy. AB - OBJECTIVE: To investigate the expression of inflammatory cytokine messenger RNA (mRNA) in peripheral blood mononuclear cells of patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM). PATIENTS: Seventeen patients with HAM, 18 HTLV-I-seropositive carriers, and 10 seronegative individuals were studied. MAIN OUTCOME MEASURE: We compared the expression of tumor necrosis factor alpha (TNF-alpha), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon alpha (IFN-alpha), IFN-beta, and IFN gamma, and interleukin 1 alpha (IL-1 alpha) and IL-1 beta by reverse transcriptase-polymerase chain reaction. RESULTS: In patients with HAM, the reverse transcriptase-polymerase chain reaction products of TNF-alpha, GM-CSF, IFN-gamma, and IL-1 alpha were detected in significantly higher incidences than in HTLV-I-seropositive carriers and seronegative controls. Furthermore, simultaneous mRNA expression of three or more of these four cytokines was detected in all patients with HAM compared with only 21.4% of HTLV-I-seropositive carriers. By contrast, there was no significant difference in mRNA expression of IFN-alpha, IFN-beta, and IL-1 beta among patients with HAM, HTLV-I-seropositive carriers, and HTLV-I-seronegative controls. CONCLUSIONS: An exaggerated mRNA expression of several inflammatory cytokines, including TNF-alpha, GM-CSF, IFN gamma, and IL-1 alpha, was demonstrated in peripheral blood mononuclear cells of patients with HAM. Moreover, transcripts of these cytokines were simultaneously up-regulated in patients with HAM, suggesting that an inflammatory state in the central nervous system may be related to the pathogenesis of HAM. PMID- 7872882 TI - Migraine prophylaxis with divalproex. AB - OBJECTIVE: To compare the effectiveness and safety of divalproex sodium (Depakote) and placebo in the prophylaxis of migraine headache. DESIGN: Multicenter, double-blind, randomized, placebo-controlled investigation, having a 4-week, single-blind placebo baseline phase and a 12-week treatment phase (4-week dose adjustment, 8-week maintenance). SETTING: Eight headache/neurology clinics throughout the United States. PATIENTS: One hundred seven patients randomized to divalproex or placebo (2:1 ratio): 70 receiving divalproex and 37 receiving placebo. INTERVENTION: Divalproex and placebo dosages titrated in blinded fashion during dose adjustment period to achieve actual/sham trough valproate sodium concentrations of approximately 70 to 120 mg/L. MEASUREMENTS AND MAIN RESULTS: During the treatment phase, the mean migraine headache frequency per 4 weeks was 3.5 in the divalproex group and 5.7 in the placebo group (p < or = .001), compared with 6.0 and 6.4, respectively, during the baseline phase. Forty-eight percent of divalproex-treated patients and 14% of placebo-treated patients showed a 50% or greater reduction in migraine headache frequency from the baseline phase (P < .001). Among those with migraine headaches, divalproex-treated patients reported significantly less functional restriction than placebo-treated patients and used significantly less symptomatic medication per episode. No significant treatment group differences were observed in average peak severity or duration of individual migraine headaches. Treatment was stopped in 13% of divalproex-treated patients and 5% of placebo-treated patients because of intolerance (P, not significant). CONCLUSIONS: Divalproex is an effective prophylactic drug for patients with migraine headaches and is generally well tolerated. PMID- 7872883 TI - The relation of spike foci and of clinical seizure characteristics to different patterns of mesial temporal atrophy. AB - We reviewed clinical data and scalp electroencephalograms in 61 consecutive patients with temporal lobe epilepsy and mesial temporal atrophy assessed with volumetric magnetic resonance imaging: 39 patients had unilateral and 22 patients had bilateral atrophy. We attempted to determine whether any aspects of seizure symptoms and any electrographic features could be correlated to degree and anatomic pattern of mesial temporal atrophy. Spikes were always confined to temporal regions and were frequently bilateral without a statistically significant difference between patients with unilateral atrophy (33%) and those with bilateral atrophy (50%). Twenty-five of 40 foci associated with amygdala atrophy had maximum field over the anterior temporal regions. In contrast, 19 of 19 foci with isolated hippocampal formation atrophy were never maximum anteriorly. Secondarily generalized seizures and temporal lobe syncopes were correlated with anatomically extensive, particularly amygdala, atrophy. Prolonged postictal confusion was always associated with bitemporal abnormalities in the form of atrophy or spiking. These results explain some of the variability in the clinical and electrographic manifestations of temporal epilepsy and outline the specific role of amygdala involvement in addition to the commonly reported hippocampal atrophy. PMID- 7872884 TI - Some specific clinical features differentiate multiple system atrophy (striatonigral variety) from Parkinson's disease. AB - OBJECTIVE: The clinical recognition of multiple system atrophy (MSA) in patients presenting with parkinsonian signs is difficult. We attempted to verify the predictive value of some pointers that are used in clinical practice. DESIGN: Sixteen consecutive patients with pathologically confirmed MSA who presented with a parkinsonian syndrome over an 8-year period were studied retrospectively, and their clinical features were analyzed in detail. SETTING: Parkinson's Disease Society, Brain Tissue Bank, Institute of Neurology, London, England. PATIENTS: Sixteen patients with pathologically proven MSA who presented with parkinsonian syndrome in the first 3 years since disease onset. METHODS: Clinical features that were analyzed included the rapidity of disease progression, the relative symmetry of symptom onset, the presence or absence of tremor at initial presentation, the therapeutic response to levodopa and the associated presence of autonomic dysfunction. Fourteen of the 16 patients also had a computed tomographic scan of the brain performed. The frequency of selected items in MSA was compared with that found in 20 pathologically confirmed cases of Parkinson's disease and 16 pathologically confirmed cases of progressive supranuclear palsy (Steele-Richardson-Olszewski disease). RESULTS: It was found that a probability scale based on five selected items discriminated MSA with a pure parkinsonian presentation from Parkinson's disease, but not from progressive supranuclear palsy. Patients affected by the latter disorder, however, commonly presented with additional clinical features (supranuclear vertical down-gaze palsy, axial dystonia, and cognitive impairment), which helped to differentiate it from MSA. PMID- 7872885 TI - A positron emission tomography study of cerebral activation associated with essential and writing tremor. AB - OBJECTIVE: To compare the abnormal patterns of cerebral activation associated with essential and writing tremors. DESIGN: Positron emission tomography using oxygen 15-labeled water was utilized to determine regional cerebral blood flow. Positron emission tomography images that were taken of the brain in individual patients were coregistered with magnetic resonance images of the same brain to ascertain accurate localization of cerebral activation in single patients. Patients with essential tremor underwent scanning at rest, during involuntary postural tremor, and during passive wrist oscillation. Normal control subjects underwent scanning at rest and during voluntary and passive wrist oscillation. Patients with writing tremor underwent scanning while they were holding a pen to paper with consequent involuntary tremor and again while they were holding a pen in the same supinated arm without tremor. SETTING: Research hospital. PATIENTS OR OTHER PARTICIPANTS: Seven patients with essential tremor, six patients with writing tremor, and six matched control subjects. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Regional cerebral blood flow. RESULTS: Essential tremor was associated with abnormal bilateral cerebellar, red nuclear, and thalamic activation. Writing tremor was also associated with abnormal bilateral cerebellar activation. Voluntary wrist oscillation in control subjects caused only ipsilateral cerebellar activation. These findings were evident in single patients, when positron emission tomography images were coregistered with magnetic resonance images and on group analysis of the pooled positron emission tomography data after transformation into stereotaxic space. CONCLUSION: These results indicate that both essential and writing tremors are associated with abnormal bilateral overactivity of cerebellar connections. PMID- 7872886 TI - Patterns of deterioration in senile dementia of the Alzheimer type. AB - OBJECTIVE: To determine rates of decline in Alzheimer's disease. DESIGN: A longitudinal review of patients diagnosed as having dementia during life, tested serially with the Extended Scale for Dementia, and confirmed by autopsy as having Alzheimer's disease. SUBJECTS AND SETTING: Twenty-nine dead patients with Alzheimer's disease from the participants in the University of Western Ontario Dementia Study Project, confirmed at autopsy as having Alzheimer's disease. METHODS: Analysis of the Extended Scale for Dementia data according to a trilinear model. FINDINGS: In the middle phase of the trilinear model, there was a mean annual change of 13% (range, 2.5% to 51.7%). CONCLUSIONS: It is likely that the common method of averaging a group of different individual scores from the initial and middle phases of observation of Alzheimer's disease collapses together individuals at different stages of the disorder, some of whom are in the initial plateau phase and whose conditions are not declining rapidly. The trilinear model of decline avoids this difficulty and the present study provides postmortem confirmed figures on rate of change. PMID- 7872887 TI - Positron emission tomography measures of benzodiazepine binding in Alzheimer's disease. AB - OBJECTIVE: To evaluate the integrity of neurons and neuropil in metabolically affected association cortices of patients with Alzheimer's disease by measuring central benzodiazepine binding sites with the use of positron emission tomography. DESIGN: In patients with Alzheimer's disease, we determined the cerebral distribution of flumazenil tagged with carbon 11 ([11C]flumazenil), a ligand that binds to the gamma-aminobutyric acid A (GABAA) receptor complex, and the distribution of fludeoxyglucose tagged with fluorine 18 fludeoxyglucose F 18), a measure of local cerebral glucose metabolism. Tracer kinetic analysis was applied to quantify data in regions of interest. These data were compared with those of normal control subjects. SUBJECTS: Patients with probable Alzheimer's disease ([11C]flumazenil, n = 13; fludeoxyglucose F 18, n = 11) and normal elderly control subjects ([11C]flumazenil, n = 6; fludeoxyglucose F 18, n = 10). RESULTS: Significant decreases of the [11C]flumazenil transport rate were found in hypometabolic parietal and temporal association cortices, but [11C]flumazenil binding was not significantly decreased. CONCLUSIONS: When measured in living patients, association cortical benzodiazepine binding sites are relatively preserved, suggesting structurally intact cortical neuropil underlying the glucose hypometabolism identified in Alzheimer's disease. PMID- 7872888 TI - Violent sleep-related behavior leading to subdural hemorrhage. AB - OBJECTIVE: To polysomnographically determine, using split-screen electroencephalographic-video analysis, the cause of violent sleep-related activity in a patient whose differential diagnosis includes sleep walking (somnambulism), pavor incubus (adult night terrors), nocturnal seizures, psychogenic wandering, and rapid eye movement sleep behavior disorder. SETTING: The patient was referred to the University of Iowa, Department of Neurology Sleep Disorders Center, Iowa City, from the local community to evaluate a history of violent dreams associated with injury. The subject presented with a subdural hemorrhage that was discovered with magnetic resonance imaging. OUTCOME: The diagnosis of rapid eye movement sleep behavior disorder was confirmed after a characteristic spell of violent behavior, with an associated dream, was captured polysomnographically. PMID- 7872889 TI - Plain radiological findings in Meniere's disease. AB - In order to investigate the characteristics of plain radiography of Meniere's disease, the degree of the pneumatization and the distance between the sigmoid plate and the bony wall of the vestibule in Schuller's view were examined in patients with unilateral and bilateral Meniere's disease, non-Meniere vertiginous disease and healthy subjects. There was no difference of the degree of pneumatization and the distance among the patients with Meniere's disease, the non-Meniere inner ear disease group and in healthy subjects. The distance of the unaffected ear was significantly shorter in patients showing a shorter distance of the affected ear. There was no relationship between the distance and age of onset of the disease, and duration of the disease. Therefore, it is concluded that the dysfunction of endolymphatic sac does not always reflect poor mastoid pneumatization and/or shorter distance in the plain radiography and that other etiological mechanisms such as autoimmune disease should be considered in some patients having evidence of endolymphatic hydrops. PMID- 7872890 TI - A new evaluation of vestibular compensation. AB - Vestibular compensation process in six patients was examined by means of static (SPG) and kinetic posturography (KPG). SPG was recorded by a stabilometer during standing and KPG was recorded by POLGON so that angular change of shoulder in the frontal plane was measured during stepping. The subjects included three cases with vestibular neuronitis, three cases with bilateral vestibular loss. In vestibular neuronitis, SPG improved earlier than KPG. As a result of vestibular training, initial high levels of SPG and KPG fall precipitously and in the case with sequela, a remarkably high level of KPG gradually decreased. In bilateral vestibular loss, abnormality of KPG tended to persist and those results would be due to the disappearance of a hip strategy. The effect of training upon the case which started from the early days was not shown. However, the case which started from 10 months after the onset showed remarkable improvement of SPG and KPG. PMID- 7872891 TI - Seasonal variations of nasal resistance in allergic rhinitis and environmental pollen counts. III: Efficacy of antiallergic agents. AB - We previously reported that, in a patient with Japanese cedar pollinosis, preseasonal increase in total nasal airway resistance (NAR) possibly caused from circannual endogenous rhythm was suppressed by preseasonal systemic administration of antiallergic agent. In this study, in order to determine the influence of preseasonal use of a topical antiallergic agent and seasonal administration of a peroral antiallergic agent, we made measurement of nasal airway resistance and pollen counts under the previous respective conditions in separated years. Preseasonal high mean values of total NAR for a couple of weeks was not suppressed by the preseasonal topical administration of ketotifen nasal spray in 1992 which was a low pollen season (974/cm2). However, the patient did not complained of severe episodes of hay fever at all throughout the season. Preseasonal increases in mean values of total NAR were observed in 1993 which was a high Japanese cedar pollen season (4,875/cm2) with NAR the same as untreated seasons. This may have been because the patient was not treated with preseasonal use of peroral azelastine. On extremely high Japanese cedar pollen count days further increased NAR occurred in the patient. The patient experienced relatively severe hay fever episodes, but used no other anti-histamine nor topical steroid during the season. PMID- 7872893 TI - Enhancement of platelet aggregation in patients with nasopharyngeal carcinoma. AB - The ADP-induced platelet aggregation in 157 patients with nasopharyngeal carcinoma (NPC) in South China was estimated. The difference between the maximum platelet aggregation rate (MAR) in the control group and the MAR of patients with stage III/IV was significant. That is, the MAR at stage III and stage IV was significantly enhanced, as compared to that in the control group and that at stage I or stage II. The results of the present study indicate that ADP-induced platelet aggregation is enhanced in NPC patients of stage III and stage IV. PMID- 7872892 TI - Establishment of a human cell line from maxillary squamous cell carcinoma and its biological features as a stimulator for induction of cytotoxic T lymphocytes. AB - A cancer cell line named FS-1 was established from maxillary cancer of which histological diagnosis was well differentiated squamous cell carcinoma (SCC). The HLA class I typing showed that FS-1 expressed the same HLA class I antigens as those of the host lymphocytes. The chromosome analysis and nuclear DNA contents suggested that FS-1 was not a normal human cell. FS-1 is characteristic of SCC in that it grows adhesively on the surface of a culture flask. The structure of tumor tissue obtained from FS-1-transplanted nude mice is very much like the original tissue of SCC. The SCC-antigen was determined in the culture supernatant of FS-1. Autologous tumor killing activity was induced from peripheral blood lymphocytes of some patients suffering from head and neck SCC after mixed lymphocyte tumor culture with FS-1. Thus, FS-1 can serve as a useful allogeneic stimulator of SCC for induction of autologous tumor killing activity. PMID- 7872894 TI - Non-epithelial malignant neoplasms of the larynx. AB - From 1948 to 1992, 14 patients with non-epithelial malignant neoplasm of the larynx were seen in the ENT Department of the Gdansk School of Medicine. During this period, 2,249 patients with malignant laryngeal neoplasms were treated. The choice of therapy (laryngectomy, total or partial, excision by thyrotomy, irradiation or chemotherapy) depended on the size and location of the tumor and its histopathological nature. Significant for these tumors were: unchanged mucosa covering the tumor, rare metastases to the cervical lymph nodes, difficulties in estimating a histopathological diagnosis and determination, in certain types their unifocal nature. PMID- 7872895 TI - Modified combination chemotherapy of cisplatin and 5-fluorouracil in squamous cell carcinomas of the head and neck. AB - Randomized studies on the efficacy of two courses of different types of chemotherapy, including cisplatin and 5-fluorouracil (5-FU), were performed on 130 previously untreated cases with advanced squamous cell carcinomas of the head and neck. Cisplatin, followed by 120-hr continuous 5-FU infusion given in the conventional way, was administered to 60 patients (Group A), while cisplatin was administered 72 hr after the initiation of continuous 5-FU infusion in 70 other patients (Group B). The overall response rates (complete response plus partial response) were 58% in group A and 69% in group B, respectively. A superior complete response rate was obtained in cases receiving modified chemotherapy (10% in group A vs 20% in group B). There was no significant difference in the incidence of side effects between the two groups. These findings indicate that the modified cisplatin plus 5-FU combination chemotherapy tested here is more efficacious regimen than that of the conventional one to achieve high complete response rate and subsequently, to improve the survival of advanced carcinoma cases of the head and neck. PMID- 7872896 TI - Induction chemotherapy in advanced head and neck cancer. AB - Induction chemotherapy, followed by definitive treatment, was performed in patients with advanced squamous-cell carcinoma of the head and neck. In this study, carried out between 1984 and 1991, testing the effectiveness of multimodality therapy in patients with previously untreated advanced (stage III and IV) squamous-cell carcinoma of the pharynx, patients received two different induction chemotherapy regimens: cisplatin, vincristine (Oncovin) plus peplomycin (COP), and cisplatin plus continuous 120-hr 5-fluorouracil (5-FU) infusion (CF) for two courses. Overall response rates (complete response plus partial response) to each of the two induction chemotherapy regimens were high: 76 and 82%, respectively. Superior complete response rate in the group receiving CF therapy was 16% versus 10% for COP therapy. Responders to induction chemotherapy had significantly better survival compared with non-responders. The toxicity of these two regimens was tolerable and manageable. It is indispensable to develop the more efficacious chemotherapy regimen with the potential to induce complete disappearance of tumors in patients with advanced head and neck carcinomas. PMID- 7872897 TI - Acinic cell carcinoma of the trachea. AB - Acinic cell carcinoma (ACC) appears primarily in the parotid gland. It is extremely rare in the respiratory tract and only a few cases of ACC in the lungs, larynx, nose, and paranasal sinuses have been described. We present here a case of ACC located in the trachea and discuss possible therapeutic strategies in the light of this tumor behavior relating to other sites. PMID- 7872898 TI - Giant tumor formed by nodular fasciitis of the pharynx: a case report. AB - Nodular fasciitis caused a benign tumor which is composed of fibrous tissue. The most commonly affected site is the upper extremity, which accounts for half of all cases. Ten to 20% of the lesions occur in the head and neck area, most of which are subcutaneous. We report a case of nodular fasciitis, which presented as an unusually large submucosal tumor of the pharynx. The tumor was extended from the retropharyngeal to the parapharyngeal space, and it was measured 8 x 4 x 3 cm in size. Since nodular fasciitis is known for the spontaneous regression, the tumor was transorally debulked by the use of YAG laser. PMID- 7872899 TI - The efficacy of K-edge filters in diagnostic radiology. AB - The application of K-edge filters in diagnostic radiology has been investigated by many workers for over twenty years. These investigations have analysed the effects of such filters on image quality and radiation dose as well as the practicalities of their application. This paper presents a synopsis of the published works and concludes that K-edge filters do not perceptibly improve image quality and make only limited reductions in patient dose. K-edge filters are also costly to purchase and potentially result in a reduction in the cost effectiveness of x-ray examinations by increasing the x-ray tube loading. Equivalent contrast enhancement and dose reductions can be achieved by the assiduous choice of non-selective filters. PMID- 7872900 TI - Thermoluminescence dosimetry and its applications in medicine--Part 1: Physics, materials and equipment. AB - Thermoluminescence dosimetry (TLD) is a versatile tool for the assessment of dose from ionising radiation. The wide variety of TLD materials and their different physical forms allow the determination of different radiation qualities at dose levels from microGy to kGy. Major advantages of TL dosimeters are their small physical size and that no cables or auxiliary equipment is required during the dose measurement. This makes them well suited for a wide range of applications in medicine. However, while larger institutions with extensive experience in TLD commonly achieve quite good results, thermoluminescence dosimetry appears a bit like a black art for physicists who attempt to set up a TLD system for the first time. Therefore, the present article aims at summarising the relevant literature describing problems and possible pitfalls in the evaluation of TLD readings. The second part of the review (to be published) will discuss typical applications of TLD in medicine. Most applications and the major part of the literature are based on lithium fluoride doped with magnesium and titanium (LiF:Mg,Ti). However, other materials such as CaSO4:Dy are widely used, and some more recent TL materials such as LiF:Mg,Cu,P show great potential for radiation dosimetry. Therefore, the present article while focusing on LiF:Mg,Ti also includes other TLD materials of interest for dosimetry in the medical field. Furthermore, TLD apparatus and a variety of TLD applications and techniques shall be discussed with two intentions: firstly to give an update of TLD in medicine, and secondly to enable readers to set up or optimise their own TLD system. PMID- 7872901 TI - Simple uniformity and penetration phantoms for the quality assurance of ultrasound scanners. AB - A pair of polyethylene bottles filled with tissue-mimicking gel provides a quick and economical method for sonographers in small hospitals and clinics to perform quality assurance on ultrasound scanners. The uniformity phantom filled with a homogeneous low attenuation gel provides a visual display of the spatial sensitivity of the probe's scanning pattern, and has proved particularly effective for detecting insensitive elements in transducer arrays. The penetration phantom contains a tissue equivalent attenuating wedge, which allows the penetration depth of the system to be measured under standard conditions. Any loss of system sensitivity will be reflected as a long term reduction in the measured penetration. PMID- 7872902 TI - Current and energy in external cardiac defibrillation. AB - External (Transthoracic) defibrillation is achieved by passing a large uniaxial current through the chest for a brief period of time. This current is determined by 1) the applied voltage and 2) the transthoracic impedance (TTI). In modern defibrillators the source of voltage is universally from a charged capacitor, the discharge waveform being modified in some cases by the inclusion of an inductor in the discharge circuit (Lown & Edmark waveforms, fig. 1), in others by direct discharge of a capacitor, such discharge being electrically truncated after a given period of time (Truncated Exponential, fig. 1). Although it is current that is responsible for successful defibrillation, defibrillator output is most commonly measured in units of energy (Joules) which is easily calculated knowing the voltage to which the defibrillation capacitor has been charged. Recent measurements of TTI show wide variations from 28 to 150 ohms3. Attempts at defibrillation (assuming the same energy setting) will thus result in a wide range of delivered currents. It is known that high defibrillation currents produce myocardial damage, conversely, currents which are too low will fail to achieve defibrillation. There is increasing evidence to suggest that defibrillators employing truncated exponential (trapezoidal) waveforms may be ineffective in subjects having high TTI. Additionally, there remains a need for a "smart" defibrillator which can calculate pre-discharge TTI and automatically adjust delivered current such that it is neither too low nor too high for the patient undergoing defibrillation. PMID- 7872903 TI - A comparison of an Agfa and Kodak film-screen combination for mammography. AB - A recently introduced Agfa film-screen combination used for mammography was compared with a widely used Kodak film-screen combination. This comparison involved evaluating the image quality and calculating a reference mean glandular dose for a breast phantom recommended by the ACPSEM. The image quality and dose were evaluated for a grid and non-grid technique as well as a range of kilovoltages. For the large area test objects in the phantom, the Agfa combination performed better. This reflected the high contrast capability of this film-screen combination. For the Kodak combination a better image score was achieved for the small area objects. These objects are indicative of the modulation transfer function and resolution characteristics of the film-screen combination. The reference mean glandular dose showed that at least 20% less dose was required for the Agfa combination. Although the Agfa combination offered improved contrast and dose saving, the Kodak combination was preferred because of the better representation of the small area objects which are an important element for early detection of breast cancer. PMID- 7872904 TI - Routine linear accelerator calibration measurements and reports logged and generated by the treatment recording and verification computer. AB - A system is described for recording weekly calibration results for both photon and electron beams for two linear accelerators. The system accommodates all possible combinations of electrometers and ion chambers that can be used in the calibration procedures. The calibration data and dosimetric constants for the instrumentation are password protected with privileged access to make changes only available to the physicist manager of the therapy QA program. PMID- 7872905 TI - Isometric wedge shielding for pelvic boost external beam therapy after Curietron treatments. AB - In the treatment of carcinoma of the cervix uteri radiotherapy patients in Perth undergo a three course treatment. The treatment involves a course of external beam radiotherapy followed by a caesium--137 implant using the Curietron 2 afterloading device and finally an external beam boost dose with a block shielding the cervix. The aim of this project was to use the boost dose to compensate for the falling gradient in the summed dose profile introduced by the caesium implant. The required boost dose was calculated using sealed source dosimetry software and the measured attenuation coefficient for low melting point alloy was then used to determine the required block profile. The clinical requirement was for a dose of 85Gy to the Manchester system A points from a combination of caesium insertion and external irradiation. Due to the geometry of the caesium implant the pelvic gland regions will receive slightly more than 85Gy. Use of the block gives rise to total doses between 85.0Gy and 89.5Gy across the field at the level of the A points. At positions 25mm above and below the A point level doses between 87.5Gy and 89.0Gy are achieved. PMID- 7872906 TI - The effect of test chart design and human factors on visual performance with night vision goggles. AB - In an effort to increase flight safety, it is imperative to learn as much as possible about the man-goggle interrelationship. This study was undertaken to see if type of goggle or other covariates might affect visual acuity (VA). We tested the VA of 103 aircrew with both the AN/PVS-5 and Aviator's Night Vision Imaging System (ANVIS) goggles using a Snellen vision testing chart and the new Night Vision Goggle (NVG) Resolution (Grid Type) Chart. Average VA's using ANVIS (Snellen = 20/38, Grid = 20/45) were significantly better (p < 0.01) than VA's using AN/PVS-5 (Snellen = 20/54, Grid = 20/58). Snellen VA's were better on average than Grid VA's (p < 0.001). Neither age, gender, nor NVG experience affected average VA at the 0.05 level. Average VA was significantly better (p < 0.05) for non-spectacle wearers using ANVIS goggles and for non-smokers using AN/PVS-5 goggles. Visual acuity is better with ANVIS than with AN/PVS-5 goggles, and may be affected somewhat by wearing spectacles, and by smoking. PMID- 7872907 TI - Prevalence of spatial disorientation in Indian Air Force aircrew. AB - The 1 Aero Medical Training Centre has surveyed aircrew of the Indian Air Force to determine the prevalence of Spatial Disorientation (SD), as related to aircraft stream, age, flying experience, geographical location and other operationally significant variables. The reported prevalence of SD is 75% among fighter aircrew, 64% in transport aircrew, and 55% in helicopter aircrew. Whereas the prevalence of SD does not appear to vary significantly with age and flying experience, it is higher in fully operational pilots and in pilots returning to flight duties after a ground tenure, as compared to ab-initio and type-converting pilots. PMID- 7872908 TI - Human and manikin head/neck response to +Gz acceleration when encumbered by helmets of various weights. AB - A series of +Gz impact tests were performed on the Armstrong laboratory vertical decelerator with human and manikin subjects wearing various helmet-mounted systems. The resulting data were used to quantify the effects on human dynamic response of varying helmet mass and seat acceleration as well as to provide comparisons to previously established safe limits of impact exposures. Tests with human subjects and a 97th percentile manikin were performed at seat impact levels of up to + 10 Gz for human and + 15 Gz for manikins, with standard and prototype helmet-mounted systems weighing from 3.2 to 6.6 lb. The results showed that increases in the helmet weight and seat acceleration resulted in increased compression, shear, and rotational forces on the neck. With helmet weights greater than 4.5 lb during +15 Gz impacts, neck compression force began to exceed established cadaver injury limits. PMID- 7872909 TI - Development of insulin resistance by astronauts during spaceflight. AB - Human spaceflight is associated with the loss of body protein. On Earth, insulin is an important factor in the regulation of muscle protein synthesis and breakdown. The objectives of this study were to determine whether insulin resistance occurs in spaceflight, and if the development of insulin resistance is related to the protein loss. The urinary C-peptide excretion rate was used as a marker for insulin secretion. The experiment was conducted before, during and after the 1991 9.5-d SLS-1 (Columbia) Space Shuttle mission. Dietary intake and urine output were monitored continuously for the four payload crewmembers from 11 d before launch to 7 d after landing for a total of 27 d. Data were obtained on the four payload crewmembers. Results were as follows: 1) the mean inflight C peptide excretion rates were significantly lower than either the pre- or postflight rates (p < 0.05); and 2) the inflight nitrogen balance decreased as C peptide excretion increased. PMID- 7872910 TI - The effects of strength training and centrifuge exposure on +Gz tolerance. AB - Weight training (WT) as a countermeasure to +Gz intolerance seems to be an accepted modality, but lacks convincing support in the research literature. This study examines factors associated with WT in an operational environment as a countermeasure to +Gz intolerance. Fourteen naval aviators were assigned to a WT group (n = 7) and a non-weight-trained control (NWT) group (n = 7). All subjects were tested before and after a 10-week training period for aerobic capacity (VO2max), dynamic muscular strength (Cybex II), body fat, gradual onset rate (GOR) for +Gz at a rate of +1 G.15 s-1, and finally a simulated air combat maneuver (SACM) consisting of 15 s at +4.5 Gz and +7 Gz alternating challenges to exhaustion. The results indicate the following: 1) no significant differences in any of the centrifuge variables measured between WT and NWT groups while both groups showed a time or learning effect in SACM from 175 +/- 109 to 239 +/- 110 s (grouped data df = 16, t = 2.97, p < 0.09); 2) no improvement in SACM time for subjects achieving a 300-s SACM pretest value (n = 4); and 3) for SACM times below 300 s, the WT subjects showed a greater improvement than NWT subjects (n = 11, F = 9.12, p < 0.02). The data suggest that although some subjects showed considerable strength gains, WT in a naval aviation operational setting may not provide a universal desired effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872911 TI - Power spectral and time based analysis of heart rate variability following 15 days head-down bed rest. AB - Power spectral and time based analyses were applied to the cardiac inter-beat interval (RRI) of 8 healthy men before and after 15 d of bed rest in the 6 degrees head-down tilt position (HDT) to determine changes in indices of cardiac parasympathetic and sympathetic activity after this exposure. At 24 h prior to HDT and on HDT day 15, a minimum of 256 RRI's were obtained from an electrocardiogram (ECG) while the subjects were in the supine position. RRI was subjected to power spectral and two methods of time-based analyses. Power spectral analysis demonstrated that the index of cardiac vagal activity was reduced (95.2 +/- 28.5 to 48.2 +/- 17.4 ms2) without affecting the index of cardiac sympathetic activity (1.18 +/- 0.7 to 0.69 +/- 0.4). The two methods of time-based analyses, time series and standard deviation analyses, further demonstrated a reduction of cardiac vagal activity post-HDT (5.5 +/- 4 to 4.8 +/- 0.6 ms2; and 42.8 +/- 4.8 to 33.9 +/- 3.3 ms, respectively). These data suggest that exposure to 15 d of HDT reduces cardiac vagal activity, while changes in cardiac sympathetic activity were indistinguishable. PMID- 7872912 TI - Knee-joint proprioception during 30-day 6 degrees head-down bed rest with isotonic and isokinetic exercise training. AB - To determine if daily isotonic exercise or isokinetic exercise training coupled with daily leg proprioceptive training, would influence leg proprioceptive tracking responses during bed rest (BR), 19 men (36 +/- SD 4 years, 178 +/- 7 cm, 76.8 +/- 7.8 kg) were allocated into a no-exercise (NOE) training control group (n = 5), and isotonic exercise (ITE, n = 7) and isokinetic exercise (IKE, n = 7) training groups. Exercise training was conducted during BR for two 30-min periods.d-1, 5 d.week-1. Only the IKE group performed proprioceptive training using a new isokinetic procedure with each lower extremity for 2.5 min before and after the daily exercise training sessions; proprioceptive testing occurred weekly for all groups. There were no significant differences in proprioceptive tracking scores, expressed as a percentage of the perfect score of 100, in the pre-BR ambulatory control period between the three groups. Knee extension and flexion tracking responses were unchanged with NOE during BR, but were significantly greater (*p < 0.05) at the end of BR in both exercise groups when compared with NOE responses (extension: NOE 80.7 +/- 0.7%, ITE 82.9* +/- 0.6%, IKE 86.5* +/- 0.7%; flexion: NOE 77.6 +/- 1.5%, ITE 80.0 +/- 0.8% (NS), IKE 83.6* +/- 0.8%). Although proprioceptive tracking was unchanged during BR with NOE, both isotonic exercise training (without additional proprioceptive training) and especially isokinetic exercise training when combined with daily proprioceptive training, significantly improved knee proprioceptive tracking responses after 30 d of BR. PMID- 7872913 TI - Effect of short-term unweighting on human skeletal muscle strength and size. AB - This study examined the effect of short-term unweighting on strength and size of lower limb muscle groups to predict probable responses to planned 16-d Shuttle flights. Subjects were 10 healthy males, exposed to 16 d of lower limb suspension (LLS). All ambulatory activity was performed on crutches while wearing a shoe with a 10-cm thick sole on the right foot. This eliminated ground contact by the left foot, and thereby, body weight bearing by the left lower limb. Biopsies of the left vastus lateralis muscle and T1 weighted magnetic resonance (MR) images (1.5 Tesla, TR/TE 600/20, 4 nex, 48 cm rectangular FOV, 10 mm transaxial slices at 5-mm intervals) of both thighs were used to examine muscle morphology. The in vivo speed-torque relation for the left and right quadriceps femoris (QF) muscle group was used to measure strength. Fiber type composition and average cross sectional area were not altered by LLS. The speed-torque relation for the left QF was down-shifted 12% (p < 0.05) after LLS. There was no effect of speed or type of muscle action (eccentric, isometric, or concentric). The speed-torque relation for the right QF showed no change after LLS. Average cross-sectional area of the left QF in eight MR images of the mid-thigh decreased (p < 0.05) 8% with LLS (70 +/- 3 to 64 +/- 4 cm2), while the right QF showed no change (72 +/- 4 to 72 +/- 4 cm2). The hamstring muscle group showed no change in average cross-sectional area after LLS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872914 TI - Normoxic, hyperoxic, and hypoxic ventilation in rats continuously exposed for 60 h to 1 ATA O2. AB - Continuous assessment of ventilation during normobaric hyperoxic exposure may help differentiate between the various effects of hyperoxia on ventilation. Ten rats were exposed continuously to hyperoxia for 60 h with intermittent measurement of ventilation in normoxia, a high-oxygen-mixture (FIO2 > 85%) and hypoxia (FIO2 approximately 1.5%). From the measured parameters of inspiratory and expiratory times (TI and TE) and tidal volume (VT), we calculated breathing frequency (f), minute ventilation (VI), inspiratory drive (VT/TI), TI/(TI+TE) and hypoxic ventilatory drive. Normoxic and high-oxygen-mixture VT increased and f decreased mainly due to increased TI, with no effect on normoxic VI. Hypoxic f and VI decreased as a function of exposure time. The fact that the increase in normoxic VT between 13 and 22 h is followed by an increase in TI between 22 and 30 h, excludes the possibility that sensitization of airway C-fiber receptors causes the increase in VT. There was no correlation between HVD and the inspiratory drive. There would appear to be two stages in O2 toxicity of the ventilatory system: in the first stage, the main effect is on the chemoreflex and mechanoreflex systems, whereas beyond 50 h there are other effects on the lung. PMID- 7872915 TI - Thoracoscopic management of spontaneous pneumothorax allows prompt return to aviation duties. AB - Primary spontaneous pneumothorax, a disease of young adults, is occasionally encountered in aviation personnel. Surgical intervention is often recommended after the first episode for those patients involved in aviation or diving duties due to the increased risk of recurrence secondary to barotrauma. Thoracoscopic surgery can be used effectively to resect the causative blebs or bullae and to perform a mechanical pleurodeisis. When compared to the traditional open technique, post-operative recovery time is less with this approach and allows more rapid return to aviation duties. Thoracoscopic surgery should be considered in all cases of spontaneous pneumothorax encountered in aviators. PMID- 7872916 TI - A new source for vestibular illusions in high agility aircraft. AB - The enhanced maneuverability aircraft of the future will expose pilots to combinations of conventional translational accelerations as well as extraordinary angular accelerations. This flight regime, combined with the intense concentration required for combat maneuvering, will make motion-induced illusions more perilous than in existing aircraft. Although there are many causes for disorientation, theoretical analysis indicates two in particular, the "G-excess" and "cross-coupling" illusions, may be invoked by a new and distinctly different stimulus. These two illusions, which are both typically induced by motion of the pilot's head, may in addition be created by rotation of the aircraft with respect to its flight path. After comparing typical pilot head movements to projected decoupled angular motion capabilities of supermaneuverable aircraft, we conclude that the potential exists for G-excess or cross-coupling illusions in a high agility aircraft independent of pilot head motion with respect to the aircraft. PMID- 7872917 TI - Dynamic characteristics of centrifuges. AB - In specifications of high performance human centrifuges, different definitions of the term "G-load onset rate" occur. This paper compares four of these definitions and discusses the motivation and its advantages and disadvantages from the technical point of view. The four definitions are applied to a high performance human centrifuge to generate Gz load versus time profiles with constant rates of G onset. In order to illustrate and measure the differences between the different methods, some evaluation parameters like "overall transition time" (time between two different g levels), and "lower transition time" (time to reach the constant onset rate from the lower g-base level) are developed. Further, the influence of a tolerance threshold for the Gx- and Gy-load components in a Gz load profile on the evaluation parameters are discussed. The admission of a relative small tolerance threshold (< or = 0.3 g) leads to a drastic reduction (40%-50%) of the evaluation parameters. PMID- 7872918 TI - Diabetes mellitus, advances and their implications for aerospace medicine. AB - The authors describe a case of Type 1 diabetes mellitus (insulin dependent) in a 34-year-old fighter pilot, which included a 15-month remission ("honeymoon period"). The pathogenesis, characteristics, diagnosis, evaluation, and the aeromedical implications of Type 1 diabetes are discussed. The use of C-peptide values in accessing beta cell function is also discussed. The risk of poorly controlled diabetes, diabetic ketoacidosis, and visual acuity fluctuations were major reasons to disqualify this individual when in remission. The importance of determining the type of diabetes for prognosis and aeromedical disposition is stressed. PMID- 7872919 TI - Publishing the Journal of the Aerospace Medical Association: 1929-1981. AB - The author served as Editor-in-Chief of this Journal from 1959 through 1980, a period which included two title changes and an explosion of information about aerospace medicine and related fields. He reviews the history of the Journal from its establishment in 1929 through the periods of growth during World War II and the coming of the Space Age. PMID- 7872920 TI - 29th Annual Harry G. Armstrong Lecture: the human space enterprise in the 21st century. PMID- 7872921 TI - An operational definition for spatial disorientation. AB - Spatial disorientation (SD) is a term which continues to have different meanings for different classes of people involved with aviation. The advent of new terms like "situational awareness" (SA), has only added to the plethora of existing definitions, leading to a difference of opinion among researchers worldwide. Lack of agreement regarding the semantics of SD among various aircraft accident investigators leads to different yardsticks in determining whether or not an accident is SD-related. These definitional differences do not allow for inter-Air Force comparisons of SD accident data, and a valuable opportunity to learn from the experience of others is lost. The authors examine the existing definitions, and propose a new practical operational definition of SD, for use in investigation and classification of aircraft accidents. PMID- 7872922 TI - The four C's of flying. PMID- 7872923 TI - You're the flight surgeon: a case of amoebic dysentery. PMID- 7872924 TI - Pharyngeal angioedema from oxygen. PMID- 7872925 TI - Fixed vs. formed aircrews and safety. PMID- 7872926 TI - Pharo Gagge and aeromedical research. PMID- 7872927 TI - Ballooning. PMID- 7872928 TI - Genetic and environmental variation in Eysenck Personality Questionnaire scales measured on Australian adolescent twins. AB - The Eysenck Personality Questionnaire was administered to 1400 Australian twin pairs aged 11 to 18, and the data were analyzed by a multivariate normal model using the software FISHER. For each scale, attempts were made to transform to normality, about a mean modeled separately for each sex as a quadratic function of age. Variances and covariances were estimated for each sex-zygosity group as a monotone function of age. Evidence for genetic sources of variation were assessed in part by fitting models which allowed for age-dependent, sex-specific, and correlated additive genetic factors, and age-dependent and sex-specific environmental factors, under the assumption that effects of environmental factors common to twin pairs are independent of zygosity. Evidence for genetic factors independent of age and sex was most compelling for Psychoticism and Neuroticism. For Extraversion, if genetic factors exist they would be mostly sex-specific and age-dependent. For the Lie scale there was evidence for, at most, a small component of genetic variation. PMID- 7872929 TI - Physiological evidence for genetically mediated sibling recognition in mice. AB - The kin selection theory predicts that individuals would behave differently toward one another, depending on their genetic relatedness. Kin discrimination has been demonstrated in mice from social behavior, and previous familiarity, as well as familiarity with the partner's phenotype, has been postulated to represent proximate mechanisms. It has already been demonstrated that siblings' reunion resulted in a decrease in pain sensitivity that is mediated by endogenous opioids. In this study, using a cross-transferring design, it is shown that genetic relatedness with the male partner, independently of postnatal association, is responsible for changes in nociceptive threshold. Conversely, previous association till weaning has no effect on pain sensitivity. These data suggest that endogenous opioids activity and social behavior represent indices of different processes: the recognition of related animals and the discrimination of familiar (and also usually related) subjects, respectively. PMID- 7872930 TI - Absence of an association between motor coordination and spatial orientation in lurcher mutant mice. AB - Lurcher mutant mice were impaired in spatial orientation and motor coordination in comparison to normal mice. Both groups improved across days in both invisible and visible water maze platform conditions. Contrary to normal mice, lurcher mutants did not improve over days in terms of the time taken to reach a side-bar in a motor coordination test, an indication of defective motor learning. However, lurchers were able to stay on the bar longer across days. These results indicate that motor learning deficits in this cerebellar-damaged animal are not absolute but dependent on the type of measurement attempted. There was no correlation between motor coordination and spatial orientation for normal mice. A similar absence of correlation was noted for lurcher mutants, except for falling latencies in the coat-hanger test during the middle of training. PMID- 7872931 TI - Implicit and explicit memory bias in anxiety: a conceptual replication. AB - Williams, Watts, MacLeod and Mathews' (1988) [Cognitive psychology and the emotional disorders. Chichester, Wiley] model of anxiety and cognition leads to the prediction that anxious subjects will show an implicit, but not an explicit, memory advantage for threat-related information. Mathews, Mogg, May and Eysenck (1989) [Journal of Abnormal Psychology, 98, 401-407] obtained marginally significant support for this prediction in an experiment that tested memory using word stem completion tasks following a self-referent encoding procedure. However, neither the reliability nor generality of these findings have been established. The current experiment was designed to provide a conceptual replication of Mathews et al.'s study, using different tests of implicit memory (i.e. tachistoscopic identification) and explicit memory (i.e. recognition) and an alternative type of encoding task (i.e. colour naming stimulus words). 16 generalised anxiety disorder patients, and 16 non-anxious control subjects were tested. As predicted, the anxiety patients showed a relative implicit memory advantage for threat-related stimulus words, while the two subject groups did not differ in their pattern of explicit memory performance. These results support the predictions generated by Williams et al.'s model of anxiety and cognition. PMID- 7872932 TI - The assessment of obesity: theoretical background and practical advice. AB - Developments in understanding the causes and consequences of obesity have important implications for the assessment of weight problems. Simple measurement of body weight is no longer sufficient. The evaluation should include measures of body composition, dietary quality, energy expenditure, risk factor status and body image. In this paper, the arguments in favour of a broader-based evaluation of obesity are presented and a range of assessment methods are discussed. PMID- 7872933 TI - The structure of obsessive-compulsive symptoms. AB - In the present study, the structure of obsessive-compulsive symptoms was investigated by means of the Padua Inventory (PI). Simultaneous Components Analysis on data from obsessive-compulsives (n = 206), patients with other anxiety disorders (n = 222), and a non clinical sample (n = 430) revealed a five factor solution. These factors are: (I) impulses; (II) washing; (III) checking; (IV) rumination; and (V) precision. Forty-one items were selected as measure of these factors. The reliability for the five subscales, assessing each of the five factors, was found to be satisfactory to excellent. Four subscales (washing, checking, rumination and precision) discriminated between panic disorder patients, social phobics and normals on the one hand and obsessive compulsives on the other. The Impulses subscale discriminated between obsessive-compulsives on the one hand and normals on the other, but not between obsessive-compulsives and social phobics or panic patients. Some evidence in support of the construct validity was found. The Padua Inventory-Revised (41-items) appears to measure the structure of obsessive compulsive symptoms: The main types of behaviours and obsessions as seen clinically are assessed by this questionnaire, apart from obsessional slowness. PMID- 7872934 TI - How does cognitive therapy prevent depressive relapse and why should attentional control (mindfulness) training help? AB - There is encouraging evidence that structured psychological treatments for depression, in particular cognitive therapy, can reduce subsequent relapse after the period of initial treatment has been completed. However, there is a continuing need for prophylactic psychological approaches that can be administered to recovered patients in euthymic mood. An information-processing analysis of depressive maintenance and relapse is used to define the requirements for effective prevention, and to propose mechanisms through which cognitive therapy achieves its prophylactic effects. This analysis suggests that similar effects can be achieved using techniques of stress-reduction based on the skills of attentional control taught in mindfulness meditation. An information processing analysis is presented of mindfulness and mindlessness, and of their relevance to preventing depressive relapse. This analysis provides the basis for the development of Attentional Control Training, a new approach to preventing relapse that integrates features of cognitive therapy and mindfulness training and is applicable to recovered depressed patients. PMID- 7872935 TI - Perspectives on depressive realism: implications for cognitive theory of depression. AB - Beck's cognitive theory of depression has provided a successful description of depressive thinking, with one major exception. The hypothesis that depressed people show biased negative thinking seems contradicted by research indicating that Ss scoring 9 or above on the Beck Depression Inventory were more accurate than their nondepressed counterparts in judging contingencies between their responses and outcomes, seemingly showing "depressive realism". Depressive realism research has attracted attention in numerous areas of psychology, along with critical commentary focused on such issues as whether realism is limited to mild depressive states, whether laboratory tasks are sufficient to document realism, and whether realism is a general characteristic of either depressed or nondepressed people. We analyze the main critiques and show how debates about depressive realism can be heuristic for refinement of cognitive theory of depression. PMID- 7872936 TI - Chronic low back pain and inaccurate predictions of pain: is being too tough a risk factor for the development and maintenance of chronic pain? AB - The present study tests whether chronic low back pain (CLBP) patients show a tendency to overpredict or to underpredict pain. Twenty CLBP patients and 20 healthy controls underwent 6 trials of laboratory induced pressure pain. Ratings of predicted and experienced pain intensity were obtained. In contradiction with the hypothesis that CLBP patients show a generalized tendency to overpredict pain, CLBP patients showed a tendency to underpredict the laboratory pain, whereas controls appeared to be more accurate. This finding replicates a previous finding, that there may be a substantial group of CLBP patients who underestimate pain. The tendency to underpredict pain may constitute a risk factor for the development and maintenance of CLBP. PMID- 7872937 TI - Pathological worry in major depression: a preliminary report. AB - Forty-nine Ss with the DSM-III-R generalized anxiety disorder (GAD) and 32 Ss with the DSM-III-R major depressive episode (MDE) were administered the Penn State Worry Questionnaire (PSWQ) in order to assess the frequency and severity of worrying. The PSWQ scores were almost equally elevated in Ss with GAD and MDE, indicating that high PSWQ scores may not be specific for the diagnosis of GAD. This finding also suggests that except for the uncontrollability of worry, which was not measured by the PSWQ, there may be no difference in the process of pathological worrying between Ss with GAD and MDE. The domains of worry may or may not be similar in Ss with GAD and MDE, but the experiences associated with them are likely to be different, due to different cognitive schemata in anxiety and depression. Finally, the phenomenological presentation of pathological worry may also differ in these two conditions, which calls for further research in this area. PMID- 7872938 TI - An examination of levels of agoraphobic severity in panic disorder. AB - Based on the results of previous studies, several factors believed to be related to the development of agoraphobia were simultaneously assessed in 195 panic disorder patients (57 males, 138 females) with various levels of DSM-III-R defined agoraphobia: none, mild, moderate, or severe. The four groups of patients significantly differed from each other on self-reports of phobic avoidance, although all the groups reported a similar type of panic attack. The four groups also did not significantly differ on catastrophic panic cognitions (e.g. fear of dying), fear of anxiety symptoms (anxiety sensitivity), or variables related to spontaneous panic. Neither severity or frequency of panic was predictive of severity of agoraphobia. The anticipation of panic only in relation to agoraphobic situations was predictive of severity of agoraphobia, followed by perceived lifestyle restrictions due to panic, and trait anxiety regarding ambiguous or novel situations. Regardless of level of agoraphobia, patients tended to avoid situations where they anticipated panic would occur, indicating that panic and agoraphobia do not share a unique or exclusive relationship. Panic disorder with various levels of phobic avoidance, rather than just agoraphobia, would appear to be a more valid diagnostic category. PMID- 7872939 TI - Predicting recidivism in juvenile delinquents: the role of mental health diagnoses and the qualification of conclusions by race. AB - Seventy-five male youths were evaluated while incarcerated in a juvenile facility in the state of Georgia. Twenty-one to 32 months following discharge, criminal files were examined for records of reincarceration. The recidivism rate was approximately one-third of the initial sample. Crime-related and mental health variables were entered into discriminant function analyses to determine models for predicting recidivism. For the total sample, earlier age at first arrest and higher severity of crime significantly discriminated recidivists from nonrecidivists. Presence of a substance abuse disorder appeared to be a positive prognostic indicator for nonrecidivism. Subsequently, separate sets of analyses were conducted by race, showing clearly that the results were qualified by race, and that differential processes may be operating for African-American vs Caucasian youth when considering recidivism. PMID- 7872940 TI - Heartbeat perception and panic disorder: possible explanations for discrepant findings. AB - Results on cardiac awareness in panic disorder are inconsistent. The present study attempted to clarify whether differences in instructions or the inclusion of patients taking antidepressant medication could account for these inconsistencies. 112 patients with panic disorder with agoraphobia were compared to 40 normal controls on the heartbeat perception task developed by Schandry (1981) [Schandry, R., Psychophysiology, 18, 483-488] using a standard instruction ("count all heartbeats you feel in your body") and a strict instruction ("count only those heartbeats about which you are sure"). Superior heartbeat perception for patients was only found with the standard instruction. Similarly, only with the standard instruction, patients taking medication affecting the cardiovascular system performed worse than patients without medication, as expected based on the relationship between stroke volume and heartbeat perception. The pattern of group differences indicates that agoraphobic patients have a better feeling for how fast their heart is beating than controls although these differences may be due to a tendency to interpret weak sensations as heartbeats. Furthermore, we tested in a subgroup of 40 patients whether cardiac awareness changes with exposure treatment. No changes in heartbeat perception were observed. PMID- 7872941 TI - Assessment of body image in eating disorders with the body dysmorphic disorder examination. AB - The Body Dysmorphic Disorder Examination (BDDE) has several advantages for the assessment of body image in eating disorder patients. It measures distressing self-consciousness, preoccupation with appearance, overvalued ideas about the importance of appearance to one's self-worth, and body image avoidance and checking behaviors. The BDDE is relevant for any type of appearance complaint and is not limited to weight or body shape concerns. The BDDE measures the useful targets for body image therapy. In a sample of eating disorder patients, the Body Dysmorphic Disorder Exam had good internal consistency and was significantly correlated with other measures of body image. It added new information to the discrimination of women with eating disorders from clinical and nonclinical controls beyond that provided by other measures of body image. PMID- 7872942 TI - Body image, body dysphoria, and dietary restraint: factor structure in nonclinical subjects. AB - The principal aim of this study was to examine the factor structure of several assessment methods used to measure dietary restraint, body dissatisfaction, and body image. Factor analysis was employed to identify and confirm the primary constructs measured by these assessment methods. A total of 206 undergraduate women were recruited as subjects. This sample was divided into two subsets of 100 and 106 subjects. On the first subset, principle components analysis identified three factors: body dysphoria, dietary restraint, and body image. With the second subset of subjects, confirmatory factor analysis cross-validated this factor structure. A two factor solution, body dysphoria and dietary restraint, was identified and confirmed when the body image measure was converted to a self minus-ideal discrepancy score. These findings are discussed in relation to the definition of control groups to be used in studies of anorexia and bulimia nervosa. Guidelines for the selection of measures for each of the three factors also are presented. PMID- 7872943 TI - Assessment of cognitive variable relevant to cognitive behavioral perspectives on anorexia nervosa and bulimia nervosa. AB - Several cognitive behavioral writers have described cognitions regarding food, eating, and body weight as central to the psychopathology of anorexia and bulimia. However, only preliminary efforts have been undertaken to develop valid and reliable assessment methodologies for these cognitions. This paper reviews the current status of self-report questionnaires, thought-sampling procedures, and methods from cognitive psychology as applied to the assessment of eating disorder cognitions. PMID- 7872944 TI - [Microbiological quality of fresh and stored ground meat from commercial production]. AB - In the last quarter of 1993 we investigated 295 samples of minced meat on 59 days of production (5 samples each day). EC-regulations (88/657/EEC, changed by 92/110/EEC) were considered. We looked for the total aerobic count, E. coli, Staph. aureus and Salmonella. Factors that could influence the results were examined as day of sampling, storage under defined conditions, ph-value etc. Most important for the microbiological quality of the product was the quality of the processed meat. In most cases samples fulfilled the strict microbiological requirements of the EC-regulation. After storage for 2 days at 2 degrees C there was no detectable alteration of the microflora of minced meat. Beginning with the third day total aerobic count increased significantly explainable by the increase of pseudomonads. There were problems with minced meat produced from beef, that was of lower quality and not fresh. EC-regulations can be fulfilled and are reasonable in case of industrial production when considering the quality of the processed meat and seasonal differences. Therefore microbiological quality control is justified. PMID- 7872945 TI - [Suitability of sampling methods for environmental studies in meat rendering and processing plants with European Community licenses]. AB - In EC-licensed meat rendering and processing plants microbiological test results obtained through contact slides and a highly precise swab method were compared. It was revealed that when using contact slides the absolute cfu can be determined only after prior verification with a reference method. The key provided by the manufacturer for data interpretation does not always match with results obtained by swab technique. Nevertheless, contact plates are suitable to determine the microbiological status. However, their technical deficiencies must be compensated. A simple swab method is well suited for use in meat rendering and processing plants. It is very economical due to low material costs and easy to apply by plant hygienists. The use of a seven step scale listing results up to 10(3) cfu/cm2 enables even non-experts to interpret their results reasonably. PMID- 7872946 TI - [The peripartum disease complex of the sow in commercial swine breeding. 2. The effect of prepartum bacteriuria on the peripartum and postpartum occurrence of puerperal diseases in the sow with anamnesis of urinary tract infection and vaginal-vulvar discharge]. AB - In an industrial pig production unit ten sows were selected at random. All the sows had puerperal disease in their anamnesis and all of them revealed at the time of selection--during their late pregnancy--urinary tract infection (UTI) and vaginal-vulvar discharge (VD) and most of them had significant bacteriuria a.p. All the sows were evaluated using Bilkei's MMA early detection system. The majority of the sows which have had significant bacteriuria a.p. developed a puerperal disease. PMID- 7872947 TI - [Lectin-based therapy applications from the laboratory to practice]. AB - Thorough analysis of the principles of molecular recognition is the basis for rational development of clinical applications. Currently, our knowledge is expanding, how biological information is encoded in a language of carbohydrate moieties, constituting the glycopart of cellular glycoconjugates. Carbohydrate binding proteins like lectins can specifically bind these ligands. This glycobiological interplay participates in recognitive inter- and intracellular processes that enable to devise clinical schemes with rational perspective like targeted drug delivery, non-steroidal treatment of inflammation or lectin ligand dependent treatment of infectious diseases. Besides the ligands, lectins, too, can be of therapeutical value, e.g. as biomodulators in the immune system. The rapid development within glycobiology allows to propose that certain aspects can well find their place in veterinary practice after proving their efficacy in clinical trials. PMID- 7872948 TI - [The effect of coccidiostats on the growth capacity and the survival ability of Salmonella live vaccine agents]. AB - Anticoccidial agents are obligatory feed additives during several rearing periods of poultry. The success of an oral immunization of young chicken with Salmonella live vaccines depends on the insensitivity of the vaccine strain against such anticoccidial agents because the vaccination success depends on the survival of the vaccine strain in the gut of the chick and the temporary colonization of lymphatic tissue. We investigated the in vitro sensitivity of the vaccine strain in the S. typhimurium live vaccine "Zoosaloral H" registered for the vaccination of poultry in Germany in connection with often used anticoccidial agents (Diclazuril, Monensin, Narasin and Salinomycin). No differences in growth and survival between the samples containing and lacking anticoccidial agents were found even by using double amounts of the permitted concentration of the anticoccidial agents. No negative effects of the tested anticoccidial agents on Salmonella being used as oral live vaccines in poultry should be expected. PMID- 7872949 TI - Xenobiotic carbonyl reduction and physiological steroid oxidoreduction. The pluripotency of several hydroxysteroid dehydrogenases. PMID- 7872950 TI - Differential effects of phosphodiesterase inhibitors on accumulation of cyclic AMP in isolated ventricular cardiomyocytes. AB - The intracellular actions of phosphodiesterase (PDE) inhibitors on the accumulation of cyclic nucleotides were studied in isolated ventricular cardiomyocytes from adult Sprague-Dawley rats. Elevated levels of cyclic AMP, due to the effects of selective PDE inhibitors, were detected only when the levels of cyclic nucleotide were enhanced with forskolin (10 microM). The time course for the elevation of cyclic AMP levels was similar for all the PDE inhibitors tested, following the pattern of an initial rise in the first 2-4 min, proceeded by a steady state at 67 +/- 6% of the maximum stimulation. HN-10200 (2-[3-methoxy-5 methylsulfinyl-2-thienyl]-1H-imidazo-[4,5-c]- pyridine hydrochloride), a new imidazopyridine derivative, had a similar concentration-dependent profile to the structurally related compound, sulmazole (AR-L 115 BS, 2-[2-methoxy-4 methylsulfinyl)phenyl]-1H- imidazo-[4,5-b]-pyridine). Both the non-selective inhibitor, 3-isobutyl-1-methylxanthine (IBMX), and the selective PDE IV inhibitor, Ro 20-1724 (4-[(3-butoxy-4-methoxyphenyl)methyl]-2- imidazolidinone), potentiated the forskolin-stimulated levels of cyclic AMP with a much greater efficacy than sulmazole or HN-10200. The concentrations of forskolin required by IBMX, sulmazole and HN-10200 (10(-3) M) to increase levels of cyclic AMP by 4 pmol/mg protein were 3.2 x 10(-6) M, 1.32 x 10(-5) M and 1.46 x 10(-5) M, respectively. Enoximone failed to cause an increase in the levels of cyclic AMP, even when stimulated with maximal concentrations of forskolin. Furthermore, in the presence of forskolin, enoximone attenuated the response of Ro 20-1724 and IBMX in a concentration-dependent manner. Enoximone, similarly to HN-10200, sulmazole, Ro 20-1724 and IBMX did not produce any significant effect on levels of cyclic GMP under elevated conditions in the presence of sodium nitroprusside. The combined action of Ro 20-1724, with either HN-10200, sulmazole, or IBMX (10( 4) M), on intracellular levels of cyclic AMP, was not greater than the response to Ro 20-1724 alone. These data demonstrate the differential actions of PDE III and PDE IV inhibitors in rat ventricular cardiomyocytes. It is suggested that enoximone has a high selectivity for the PDE III isoenzyme so that hydrolysis of cyclic AMP by the PDE IV isoenzyme is not inhibited, in accordance with the lack of increase in cyclic AMP by enoximone in rat cardiomyocytes. HN-10200 and sulmazole, producing small increases in intracellular levels of cyclic AMP, are less selective PDE III inhibitors than enoximone.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7872951 TI - Ethylmorphine O-deethylation in isolated rat hepatocytes. Involvement of codeine O-demethylation enzyme systems. AB - The O-dealkylation of ethylmorphine (EM) and codeine (CD) to morphine (M) co segregates with debrisoquine/sparteine genetic polymorphism in man. CD O demethylation is catalysed by cytochrome P450 2D1 (CYP2D1) in rats. In the present study, the O-deethylation of EM was examined and compared with that of CD in suspensions of freshly-isolated hepatocytes prepared by a collagenase method from Wistar rats with and without CYP2D1 inhibitors. Isolated hepatocytes were also prepared from Dark Agouti (DA) rats deficient in CYP2D1, and were incubated with EM or CD. EM, CD and their metabolites were quantified by HPLC with UV detection. EM had a similar pattern of metabolism to that of CD in suspensions of hepatocytes from Wistar rats. Both EM and CD were O-dealkylated to form M plus morphine-3-glucuronide (M3G) and N-demethylated to form norethylmorphine (NEM) or norcodeine (NCD), respectively, which were further metabolized to normorphine (NM) and finally glucuronidated to normorphine-3-glucuronide (NM3G). As compared to hepatocytes from Wistar rats, DA rats were characterized by a markedly decreased formation (70 approximately 75% reduction) of M plus M3G from both EM and CD. Quinine, quinidine, propafenone and sparteine all inhibited EM O deethylation as well as CD O-demethylation. Quinine was the most potent inhibitor of both these O-dealkylations (Ki = 0.2 microM for both EM and CD, respectively). Quinine as well as the other inhibitors inhibited both EM and CD O-dealkylation competitively and with small differences in Ki versus EM and CD, respectively. The metabolism of EM to M plus M3G and that of CD to M plus M3G was highly correlated when results from the various separate cell suspensions were plotted. In conclusion all findings indicated that the enzyme responsible for O demethylation of CD, CYP2D1 was also responsible for the O-deethylation of EM to M. PMID- 7872952 TI - Meta-iodobenzylguanidine inhibits complex I and III of the respiratory chain in the human cell line Molt-4. AB - In this paper we report the effects of meta-iodobenzylguanidine (MIBG), a structural analogue of norepinephrine, on cell proliferation and several parameters related to mitochondrial respiration in Molt-4 cells. In micromolar concentrations, MIBG completely inhibited the proliferation of Molt-4 cells. In intact Molt-4 cells, a progressive increase in the lactate to pyruvate ratio was observed after incubation of these cells with glucose and increasing concentrations of MIBG. In Molt-4 cells permeabilized with digitonin, MIBG inhibited mitochondrial ATP synthesis when malate was used as a substrate. Succinate-driven synthesis of ATP was also inhibited by MIBG, although higher concentrations were required. These results indicate that apart from inhibition of complex I, MIBG inhibits at least one other complex of the respiratory chain. Measurement of the activities of the individual enzyme complexes in the presence of MIBG revealed that complex III is the other enzyme complex susceptible to inhibition by MIBG. Although maximal inhibition of ATP synthesis was observed at a concentration of 10 microM, maximal inhibition of cell proliferation was observed at a concentration of 50 microM of MIBG. This suggests that MIBG also influences other cellular processes apart from mitochondrial oxidative phosphorylation, resulting in additional inhibition of cell proliferation. PMID- 7872953 TI - Cyclic somatostatin analogs bind specifically to pI 6.1 carboxylesterase of rat liver cells. AB - The hydrophobic cyclohexapeptide cyclo(Phe-Thr-Lys-Trp-Phe-DPro) (008), an analog of somatostatin with retro sequence, was previously shown to competitively inhibit the uptake of cholate and taurocholate into isolated rat liver cells. Conversely, the competitive uptake inhibition of 008 into isolated rat hepatocytes by bile acids confirmed the observation of common binding and transport sites by bile acids and cyclosomatostatin. Furthermore the transport characteristics of 008 uptake revealed a significant and rapid binding to cell membranes. In this context it was of special interest to investigate the specificity of the binding component since specific binding of the substrate to membrane proteins could be responsible for the low Km of 008-transport. Therefore, the cyclohexapeptide 008 could be used as the ligand in affinity chromatography in order to isolate such binding proteins. The gel matrix used did not interact non-specifically with octylglucoside-solubilized proteins from isolated rat liver plasma membranes. In affinity chromatography of octylglucoside solubilized plasma membranes, two dominant proteins with apparent molecular masses of 60 and 58 kDa bound specifically to the 008 ligand. When used as ligands in affinity chromatography, these membrane-associated 60 and 58 kDa proteins bound exclusively to aromatic cyclopeptides, e.g. cyclosomatostatin 008, but not to linear peptides or taurocholate derivatives. The amino acid sequences of tryptic digests of the 008-affinity-purified 58 kDa protein were identical to the sequence of a microsomal pI6.1 carboxylesterase. Immunofluorescence of intact hepatocytes showed that this xenobiotic metabolizing enzyme is also located in sinusoidal rat liver plasma membranes and could therefore account for the extensive and specific binding of the cyclosomatostatin to sinusoidal plasma membranes of rat liver. PMID- 7872954 TI - Hepatic uptake and biliary excretion of the neuroprotectant 2,3-dihydroxy-6-nitro 7-sulfamoyl-benzo-(F)-quinoxaline in rat liver. Involvement of an organic anion transport system. AB - The hepatic uptake and biliary excretion of the neuroprotective drug 2,3 dihydroxy-6-nitro-7-sulfamoyl-benzo-(f)-quinoxaline (NBQX) was studied in rat liver. In the isolated single-pass perfused rat liver preparation NBQX was infused in protein-free Krebs-Henseleit bicarbonate buffer at input concentrations ranging from 0.5 to 15 microM. The hepatic uptake could be characterized as a pseudo first-order unidirectional process with an apparent half-life of 5.8 min. Significantly higher concentrations of NBQX were measured in bile compared to perfusate with a maximal ratio at the lowest input concentration (approx. 2400-fold). Hepatic uptake and biliary excretion of NBQX exhibited saturation at increasing input concentrations, indicating an active transport mechanism. The uptake process could be described by Michaelis-Menten kinetics resulting in a Km,uptake of 2.2 microM. The corresponding maximal uptake rate (Vmax,uptake) was calculated to be 103 nmol/min. The maximal biliary excretion rate was estimated to be 58 nmol/min. The rate-limiting factor in the overall hepatic elimination was thus biliary excretion. Co-infusion with the uricosuric drug probenecid resulted in significantly decreased hepatic uptake and biliary excretion. These data suggest that NBQX is eliminated by an organic anion transport system in rat liver which is sensitive to probenecid. PMID- 7872955 TI - Hormonal influences of detoxication in the rat ovary on enzymes in comparison with the liver. AB - Variations in the total capacity of the rat ovary to metabolize xenobiotics during different phases of the estrous cycle were studied. The level of the conjugating enzymes, phenol UDP-glucuronosyltransferase (pUDPGT; EC 2.4.1.17), phenol sulfotransferase (pST; EC 2.8.2.1) and glutathione transferases (EC 2.5.1.18) was determined in the ovary and compared with the corresponding hepatic activities. In addition, catalase (EC 1.11.1.6) and NAD(P)H: quinone oxidoreductase (EC 1.6.99.2) two other detoxifying enzymes, were assayed. In order to study the hormonal influences on detoxifying enzymes, mature rats were characterized with respect to their stage in the estrous cycle. Immature rats were treated with pregnant mare's serum gonadotropin (PMSG) for 2 or 3 days to enrich the ovaries in preovulatory follicles or corpora lutea, respectively. The present study demonstrates that ovarian pUDPGT and pST activities are increased 936% and 175%, respectively, in ovaries enriched in corpora lutea compared to ovaries from untreated immature rats. Increases in these activities in mature rats during the metestrous stage of the estrous cycle compared to the proestrous stage were also noted. In the liver pUDPGT activity is increased significantly (1.6-fold) in immature rats with ovaries enriched in preovulatory follicles compared to untreated rats. Both ovarian pST and pUDPGT activities increased in mature rats treated with PMSG ("hyperstimulated"), while in the liver only pST was increased by such treatment. Ovarian glutathione transferase activity proved not to be dependent on the hormonal fluctuations associated with the estrous cycle. However, in the liver of mature rats treated with PMSG, this activity increased 2-fold compared to the untreated immature rats. The catalase activity found in the ovarian mitochondrial fraction was approx. 10-fold higher than in the cytosolic fraction, independent of the hormonal status. Moreover, we found a significant 1.4-fold increase in peroxisomal catalase activity in the mitochondrial fraction of immature rats treated with PMSG, both when enriched in preovulatory follicles and in corpora lutea. In the liver cytosolic catalase activity decreased several-fold in immature rats following PMSG treatment. We did not find any variations in ovarian NAD(P)H: quinone oxidoreductase activity during the estrous cycle, whereas in the liver this activity decreased in the luteal phase, as it did in mature rats treated with PMSG. From this study and earlier investigations in our laboratory, we conclude that cyclic variations due to hormones of the estrous cycle of the major 7,12-dimethylbenz(a)anthracene (DMBA)-metabolizing phase I enzymes in the ovary are not accompanied by increases in the activities of the corresponding phase II enzymes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7872956 TI - Concentration-dependent binding of the chiral beta-blocker oxprenolol to isoelectric or negatively charged unilamellar vesicles. AB - Large unilamellar vesicles (LUVs) of different lipid compositions were used to study the type of binding of the beta-blocking cationic agent oxprenolol to the lipid matrix of biological membranes at a physiologic pH value of 7.4. When isoelectric membranes of pure egg lecithin or egg lecithin/cholesterol (7:3 mol/mol) were used, a linear relationship between membrane-bound and free oxprenolol indicated a constant molar partition coefficient of 54 or 44 between the liposomal and the aqueous phase over a wide concentration range of the drug up to 25 mM. This pointed to deep insertion of the drug molecules into the hydrophobic membrane interior. Drug binding to membranes of negatively charged phosphatidylserine from bovine brain was cooperative with a Hill coefficient h of 3.4 at concentrations below 0.5 mM and a molar ratio Re of bound drug per lipid of 1:10. Above drug concentrations of 2.5 mM and Re = 1:5, a constant molar partition coefficient of 33 could be estimated. R-oxprenolol or S-oxprenolol, as well as the racemic drug, showed no differences in membrane binding, even with egg lecithin LUVs containing 20 mol% of the negatively charged (2S, 4R)-N (hexadecanoyl)-4-hydroxyproline, which has a pronounced chiral headgroup. Our results suggest that enantioselective interactions of the chiral oxprenolol with the chiral lipids of biological membranes can be excluded. Furthermore, surface adsorption of the drug is probable only on the negatively charged cytosolic side of biological plasma membranes, whereas on the isoelectric exterior the cationic drug is inserted deeply into the membrane. PMID- 7872957 TI - Inhibition of thrombin and SFLLR-peptide stimulation of platelet aggregation, phospholipase A2 and Na+/H+ exchange by a thrombin receptor antagonist. AB - A thrombin receptor has been described that is activated by thrombin cleavage generating a new N-terminus. The newly exposed SFLLR-containing "tethered-ligand" then activates the receptor. In these studies, we used 3-mercapto-propionyl-Phe Cha-Cha-Arg-Lys-Pro-Asn- Asp-Lys-amide (Mpapeptide) as a thrombin receptor antagonist. This compound was capable of preventing both thrombin- and SFLLR peptide-induced platelet aggregation with little effect on collagen-induced platelet aggregation. It also prevented thrombin- and SFLLRNP-induced calcium mobilization with little effect on thromboxane receptor-activated platelet Ca2+ mobilization. Platelet membrane GTPase could be activated by peptides that activated the thrombin receptor, and the thrombin receptor antagonist also prevented receptor-stimulated GTPase activity. Platelet phospholipase A2 (PLA2) activity (measured as the release of radiolabeled arachidonic acid) and Na+/H+ exchange activation were stimulated by alpha-thrombin and by SFLLR-containing peptides. Activation of both processes with low concentrations of thrombin required thrombin's anion-binding exosite, as they were not activated by similar concentrations of gamma-thrombin, and the alpha- and zeta-thrombin activation was blocked by peptides mimicking the C-terminal region of hirudin. Stimulation of PLA2 and Na+/H+ exchange by both thrombin and SFLLR-containing peptides was inhibited by the thrombin receptor antagonist Mpa-peptide. These results support the hypothesis that thrombin stimulation of PLA2 activity and Na+/H+ exchange occurs via activation of the thrombin tethered-ligand receptor. Moreover, these data are consistent with the tethered-ligand receptor mediating most actions elicited by low concentrations of alpha-thrombin involved in human platelet activation. PMID- 7872958 TI - Photoactivated inhibition of superoxide generation and protein kinase C activity in neutrophils by blepharismin, a protozoan photodynamically active pigment. AB - Blepharismin is an endogenous photosensitizing pigment found in the protozoan Blepharisma. This pigment inhibited the generation of superoxide anion (O2-.) in neutrophils not only via a diacylglycerol-induced protein kinase C (PKC) dependent reaction but also by an arachidonate-induced PKC-independent reaction. The inhibition was light and concentration dependent for both reactions. Light activated inhibition was strong at wavelengths between 520 and 570 nm but not above 610 nm. PKC activity in neutrophils and from rat brain was inhibited by blepharismin in a light- and concentration-dependent manner. Moreover, arachidonate-activated NADPH oxidase activity in a cell-free system was also inhibited by the pigment in a light- and concentration-dependent manner. These results suggest that blepharismin inhibits NADPH oxidase activation through the non-specific inhibition of various membrane-bound enzymes and that this inhibition may also be correlated with that of PKC. PMID- 7872959 TI - Molecular properties and myocardial salvage effects of morin hydrate. AB - Morin hydrate is a bioactive pigment found in yellow Brazil wood. Recently, we reported that morin hydrate prolongs the survival of three types of cells from the human circulatory system against oxyradicals generated in vitro. The protection excels that given by equimolar concentrations of ascorbate, mannitol, and Trolox. Here, we demonstrate that, in vivo, morin hydrate at 5 mumol/kg actually reduced by > 50% the tissue necrosis in post-ischemic and reperfused rabbit hearts. Mechanistically, morin hydrate not only scavenges oxyradicals, but also moderately inhibits xanthine oxidase, a free-radical generating enzyme from the ischemic endothelium. Among other possibilities, morin hydrate appears to chelate some metal ions (e.g. Fe2+) in oxyradical formation, although this needs to be examined further. Nuclear magnetic resonance (at 500 mHz) and electron impact mass spectrometry also supported a molecular formula of C15H10O7 for morin hydrate. Only by X-ray crystallography was it clearly revealed that there are two water molecules attached by intermolecular hydrogen bonds to a morin molecule. Also, the three rings of morin hydrate approach coplanarity. This conformation favours a delocalization of electrons after oxyradical reduction, making morin an effective antioxidant. Thus, we have documented some of the molecular properties and myocardial salvage effects of morin hydrate. PMID- 7872960 TI - Expression of drug resistance-associated mdr-1, GST pi, and topoisomerase II genes during cell cycle traverse. AB - The expression of drug resistance-associated mdr-1, GST pi, and topoisomerase II genes was analyzed in cell cycle phase enriched populations of doxorubicin resistant murine leukemic P388/R-84 cells. Flow cytometric analysis of bromodeoxyuridine (BrdU) incorporation and staining with anti-BrdU antibodies was used to confirm the purity of cell cycle phase enriched populations obtained by centrifugal elutriation. Doxorubicin (DOX) and daunorubicin (DNR) accumulation was significantly lower in S-phase cells, and coincubation with verapamil (VPL) or chlorpromazine (CPZ) enhanced DOX and DNR accumulation more in S-phase than in G1- and G2/M-phase cells. While the cellular content of mdr-1 and topoisomerase II mRNAs changed, GST pi mRNA content remained constant during the cell cycle. S phase cells had about 3-fold higher mdr-1 mRNA content than G1- and G2/M-phase cells. In G1 cells, P-glycoprotein expression, as determined by C219 monoclonal antibody, was 12% less than that of S and G2/M cells. Topoisomerase II mRNA content increased with the progression of cell cycle and peaked in G2/M cells. These observations suggest that cell cycle stage related changes in expression of drug resistance markers may have a major bearing on chemosensitivity of drug resistant cells. PMID- 7872961 TI - Aberrant cell cycle inhibition pattern in human colon carcinoma cell lines after exposure to 5-fluorouracil. AB - In this report, we describe the use of two human colon carcinoma cell lines, HCT 8 and HT-29, as potential models to study DNA- and RNA-directed cytotoxicity due to 5-fluorouracil (FUra) exposure by flow microfluorimetric analysis of DNA cell content. The sensitivity of the HT-29 line (EC50 = 0.9 microM) to FUra was somewhat greater than that of the HCT-8 line (EC50 = 4 microM), but each presented a dramatically different DNA histogram after exposure to FUra. In HCT 8, an unexpected and nearly complete disappearance of cells in S-phase occurred, whereas in HT-29 the expected accumulation of cells at the G1-S border was observed. The absence of HCT-8 cells in S-phase also occurred as a result of two RNA polymerase inhibitors: actinomycin D and dichloro-D ribofuranosylbenzimidazole. However, an accumulation of cells in S-phase was observed in the presence of 5-fluorodeoxyuridine. These results suggest that in the HCT-8 cell line, FUra predominantly causes an RNA-related toxicity. By comparison, the rate of formation of 5-fluorodeoxyuridine monophosphate, the increased dUMP pool size, and low thymidylate synthase activity in the HT-29 line are consistent with its greater susceptibility to DNA-directed toxicity. Further evidence was seen in the prevention of FUra cytotoxicity by thymidine in HT-29, but not in HCT-8 cells. Similarly, Leucovorin synergized the action of FUra in HT 29 but not in HCT-8. Enzymatic correlates supporting these observations are seen in the greater activity of uridine kinase than thymidine kinase (20:1) in HCT-8 cells compared with that in HT-29 cells (4:1). PMID- 7872962 TI - Effect of clinically modeled regimens on the growth response and development of resistance in human colon carcinoma cell lines. AB - Two human colon cell lines, HCT-8 and HT-29, were exposed to 5-fluorouracil (FUra) under conditions similar to the human plasma pharmacokinetic profile achieved by a single bolus dose or a sustained i.v. infusion. The bolus treatment for 5 days caused a substantial cell kill; however, only a moderate inhibition in cell growth was obtained with sustained exposure to the clinically relevant level of 2 microM. To achieve a cell kill equivalent to the bolus method, a sustained concentration of 10 microM was required. This would constitute a 60% increase in the total area under the curve (AUC) compared with the bolus treatment. After three courses of therapy with each of the schedules, emerging cell lines displayed a similar degree of resistance. HT-29 resistant cell lines returned to the original sensitivity within a few weeks, and most of the enzymes involved in the metabolic activation of FUra returned to their pretreatment activities. However, resistance and enzymatic modifications remained in the HCT-8 line for at least 3 months. In the HCT-8 cell line derived from bolus treatment, resistance was associated with a 50-60% reduction in uridine kinase activity. In the line derived from continuous exposure, there was a 35-40% reduction in uridine kinase in addition to a greater reduction in the activity of orotate phosphoribosyltransferase. These changes in both resistant cell lines resulted in a decreased incorporation of [3H]FUra into nucleic acids and a reduced formation of di- and triphosphate nucleotides of FUra. PMID- 7872963 TI - Activation and cytotoxicity of 2-alpha-aminoacyl prodrugs of methotrexate. AB - In an effort to improve the selectivity of the anticancer drug methotrexate (MTX), a series of potential prodrugs in which the 2-amino group was acylated with various alpha-amino acids (as well as L-pyroglutamic acid) was synthesized. Such derivatives are anticipated to be hydrolysed to MTX by appropriate aminopeptidases localized (over-expressed naturally or targeted as anti-tumor antibody conjugates) in the vicinity of the tumor. The L-leucyl, L-valyl, L isoleucyl, D-alanyl and L-pyroglutamyl derivatives were assessed as to their suitability as prodrugs. Except for the L-pyroglutamyl compound, all derivatives decomposed slowly when incubated in phosphate buffer, pH 7.3; the formation of MTX was minimal. No major differences were observed when serum was included in the incubation medium, except for the L-leucyl compound, which was hydrolysed to MTX. The L-leucyl, L-valyl and L-isoleucyl derivatives were hydrolysed readily to MTX by aminopeptidase M (EC 3.4.11.2), while the L-pyroglutamyl and D-alanyl compounds were activated by pyroglutamate aminopeptidase (EC 3.4.19.3) (from Bacillus amyloliquefaciens) and D-aminopeptidase (from Ochrobactrum anthropi), respectively. When tested for inhibition of the target enzyme dihydrofolate reductase (DHFR; EC 1.5.1.3), 2-L-valyl-MTX showed inhibition two orders of magnitude poorer than that given by MTX, in agreement with the expectation that acylation of the 2-amino group reduces binding to DHFR. After treatment of this derivative with aminopeptidase M, the extent of inhibition correlated with the amount of MTX formed. MTX derivatives alone or in combination with the complementary peptidase were tested for cytotoxicity on murine L1210 cells in culture. The above-listed derivatives were considerably less cytotoxic than MTX, except for the L-leucyl derivative which showed considerable cytotoxicity. When the appropriate exogenous peptidase was included, the cytotoxicity of the activated prodrugs approached that of MTX. These results indicate that 2-L-leucyl MTX is unsuitable as a prodrug since it is activated prematurely by serum enzymes. Although the L-valyl and L-isoleucyl derivatives do not hydrolyse to MTX in serum and are readily activated, they are not ideal prodrugs since they decompose under physiological conditions; the properties of the decomposition product will have a bearing on the ultimate suitability of these compounds. 2-L Pyroglutamyl-MTX is the best candidate prodrug, showing stability and ready activation by the appropriate aminopeptidase. PMID- 7872964 TI - The antitumor drug, 1,3-bis(2-chloroethyl)-1-nitroso-urea, inactivates human nicotinamide mononucleotide adenylyltransferase. AB - Nicotinamide mononucleotide (NMN) adenylyltransferase (EC 2.7.7.1) from human placenta is rapidly inactivated by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). A similar inactivation is observed with other C- and N-nitroso compounds. The inactivation by BCNU is dependent on incubation time, temperature and BCNU concentration. Protective reagents for -SH groups, dithiothreitol and beta mercaptoethanol, and the substrate NMN are very effective in protecting NMN adenylyltransferase from BCNU inactivation and in preserving its catalytic properties, while ATP is less efficient. Incubation of BCNU-inactivated and dialysed NMN adenylyltransferase with dithiothreitol results in a partial recovery of the enzymatic activity. PMID- 7872965 TI - MHC class I and autoimmune diabetes. AB - The cause of failed self tolerance, resulting in autoimmunity is unknown, although genetic linkage to genes within the MHC class II region have been well described. We present evidence that failed self tolerance in autoimmune diabetes appears to be secondary to an antigen presenting cell defect; the diabetic antigen presenting cells fail to deliver fragments of endogenous antigens to the cell surface in the groove of MHC class I. In the diabetic NOD mouse model, this correlates with a rare allele at the Tap-1 locus, a gene that controls proper MHC class I assembly by providing fragments of endogenous peptides into the endoplasmic reticulum. We propose that MHC class I presentation of self peptides may represent a normal pathway for tolerance induction and interruption of this important class I function from any cause, including the MHC class II-linked Tap 1 and Tap-2 genes, which may result in autoreactivity. PMID- 7872966 TI - Nuclear immunostaining of hepatitis C infected hepatocytes with monoclonal antibodies to C100-3 nonstructural protein. Comparison of immunogold silver staining with other immunohistochemical methods. AB - Immunohistochemical methods have been used to localize an HCV antigen on paraffin embedded liver tissue sections by means of monoclonal antibodies to C100-3 nonstructural protein. Peroxidase-antiperoxidase, alkaline phosphatase antialkaline phosphatase, biotin-streptavidin-peroxidase and immunogold silver staining methods showed a nuclear staining of the hepatocytes in cases of chronic hepatitis with positive HCV serology, alcoholic liver disease and hepatocarcinoma. No cross reactions were observed with viral hepatitis B and delta antigens. The strongest reaction without background staining was obtained with immunogold silver staining. Nuclear localization was compared to the cytoplasmic staining described in the literature. PMID- 7872967 TI - Isolation rooms for tuberculosis control. PMID- 7872968 TI - Health care and medicine: the case for their divorce. PMID- 7872969 TI - Should all pregnant women be tested for their platelet PLA (Zw, HPA-1) phenotype? PMID- 7872970 TI - Diabetes and dialysis increase the risk of hyperacute pancreatic islet xenograft rejection by xenophile antibodies. PMID- 7872971 TI - Subacute care: the devil's in the definition. PMID- 7872972 TI - Has the Holy See become an NGO? AB - The Vatican's disruption of the Cairo population conference last week is a sign that it should in future enjoy the status of just another pressure group in relation to international negotiations. PMID- 7872973 TI - AIDS and the neurosurgeon--an update. AB - Over the past decade, acquired immunodeficiency syndrome (AIDS) has become the leading public health crisis in the United States, Western Europe, and Africa. Despite improvements in the diagnosis and treatment of AIDS-related disorders, the number of people infected with the human immunodeficiency virus (HIV-1) continues to grow, requiring a greater proportion of limited financial, medical, and human resources. Since nearly one half of symptomatic AIDS patients have neuropathologic disease, clinicians must be aware of the myriad neurologic manifestations of AIDS and use the most effective methods to diagnose and treat them. The work-up of the AIDS patient with neurologic symptoms includes a careful history and physical examination, laboratory studies, and radiographic imaging. Gadolinium-enhanced magnetic resonance (MR) imaging has become the radiographic screening study of choice. MR imaging can be used to predict which patients should undergo stereotactic biopsy before an empirical trial of antitoxoplasmosis therapy. Any patient with a mass lesion that does not respond to empirical therapy for toxoplasmosis should also undergo biopsy to exclude another treatable disorder. While the number of patients with neurological complications can be expected to increase in the near future, better imaging techniques may obviate the need for biopsy in many of these patients. The increasing threat of HIV-1 infection in the workplace requires meticulous care both in and out of the operating room to minimize accidental exposure of health-care workers. PMID- 7872974 TI - The surgery of occult spinal dysraphism. PMID- 7872975 TI - Functional stereotactic neurosurgery for psychiatric disorders: an experience in Belgium and The Netherlands. PMID- 7872976 TI - Biological markers for tumours of the brain. PMID- 7872977 TI - Histoprognosis of gliomas. PMID- 7872978 TI - Brain protection. PMID- 7872979 TI - Observation study on natural walking in the Tokyo metropolitan. AB - In this study, data on walking speed, step numbers, cadence of natural walking were collected and their relations to foot wear, clothing, luggage carried and time of the day as well as crowdedness were investigated. This survey was held in Shinjuku, Tokyo in 1991. Six thousand three hundred and seventy nine walking people were observed from 10:00 am to 5:00 pm. Ten students who were trained to observe the walking were employed for the data collection. The observed subjects were divided into three age groups, namely young (less than 30 years), middle (31 60 years) and elder (over 61 years), and their age groups were decided by the students based on their appearance. For the analysis, they were further classified into male and female groups. The factors which affect walking speed, step number and cadence were taken into consideration. It was found that young people were more sensitive to their factors in their natural walking and old people showed lower flexibility to these factors. PMID- 7872980 TI - [Effects of handgrip work and heat load on heart rate variability]. AB - The purpose of the present study was to evaluate cardiac sympathetic (SNS) and parasympathic (PNS) nervous system activities during isometric continuous and intermittent handgrip with power spectrum analysis of heart rate variability (HRV). Eight healthy men performed work at 10% maximum voluntary contraction. The sequence of tests included three different work patterns: 1) the continuous handgrip for 30 min, 2) the intermittent handgrip (10 sec contraction +5 sec relaxation) for 45 min, 3) the intermittent handgrip (10 sec contraction +10 sec relaxation) for 60 min. These experiments were performed at two different heat loads (25 degrees C and 40 degrees C, R.H. 50%). To evaluate HRV, low frequency component (0.03-0.15Hz: LFP) and high frequency component (0.15-0.5Hz: HFP) power were calculated. The SNS and PNS activities were evaluated by LFP/HFP and HFP/(HFP + LFP), respectively. Summary of the results was shown below. 1) The change of the SNS and PNS activities were not significant among the different work patterns, due to the lower work load in the present experiment. 2) The increase of HR at 25 degrees C was mediated primarily by the decrease of the PNS activities during the work periods. 3) The effects of heat loads on the SNS and PNS activities were significant. Briefly, at the same work pattern, the SNS activities at 40 degrees were higher than those at 25 degrees C, but the PNS activities at 40 degrees C were lower than those at 25 degrees C. PMID- 7872981 TI - Effects of aerobic conditioning at intensities corresponding to lactate threshold plus reduced energy intake in college-age females. AB - The effects of a 15-wk aerobic conditioning (4.2 +/- 1.3 d/wk) plus energy restriction (25 kcal/kg/d diet) program on anthropometric and physiologic attributes were studied in 16 obese women between the ages of 18 and 24. The women were divided into either an experimental (E, n = 10) group or a control (C, n = 6) group. The exercise + diet (E) group demonstrated significant reductions in body weight, both absolute and relative body fat, Katsura index, and serum triglycerides, and increases in oxygen uptake relative to lactate threshold (LT), maximal oxygen uptake, and the ratio of high-density lipoprotein cholesterol to total cholesterol. In the C group, none of the variables measured in this study remained unchanged. Thus the benefits of weight reduction without any change in fat free weight following the program were pronounced in the female university age group that we studied. In conclusion, the highly structured aerobic conditioning at intensities corresponding to LT together with a proper dietary regimen is considered optimal with respect to favorable changes in various anthropometric and physiologic attributes. The feasibility of treating obese individuals with manifestation of medical and/or psychological problems in a school setting should be a significant matter in future research. PMID- 7872982 TI - [Localized muscular load to different work patterns and heat loads during handgrip]. AB - The physiological responses and the magnitude of perceived fatigue (MPF) were estimated from eight healthy men during isometric continuous and intermittent handgrip at 10% maximum voluntary contraction (MVC). The physiological responses involved electromyogram (EMG), heart rate (HR), mean blood pressure (MBP) and forearm blood flow during contraction (FBFC) and relaxation (FBFR). The sequence of tests included three different work patterns: 1) continuous handgrip for 30 min, 2) intermittent handgrip (10 sec contraction +5 sec relaxation) for 45 min, 3) intermittent handgrip (10 sec contraction +10 sec relaxation) for 60 min. These experiments were performed on two different heat loads (25 degrees C and 40 degrees C, H.R. 50%). The results were as follows: 1) The localized muscle fatigue in the forearm was observed during the work periods. 2) The mean frequency of EMG was higher at 40 degrees C than 25 degrees C. 3) FBFR was significantly lower than FBFC at 40 degrees C. 4) MPF and MBP were little influenced by the heat load. 5) MPF correlated well with both HR and MBP. PMID- 7872983 TI - Relationship between heart rate and oxygen uptake during submaximal arm cranking in paraplegics and quadriplegics. AB - The purpose of this study was to clarify the effect of the level of spinal cord injury (SCI) and of daily exercise on the relationship between heart rate (HR) and oxygen uptake (VO2) in persons with SCI (PSCI) during an arm cranking exercise. Eighteen PSCI were divided into three groups according to the level of SCI; 4 quadriplegics (C6-C8), 7 high- level paraplegics (T3-T8), and 7 low-level paraplegics (T10-L2). In the relationship between HR and VO2, the higher the level of SCI, the smaller the slope of regression line, that means the HR at a given VO2 become larger as level of SCI was higher. Significant differences were found among these regression lines (P < 0.01). In addition, the regression lines between HR and VO2 in active persons tended to shift toward upper in comparison with those in inactive persons. The present investigation clearly shows that the HR-VO2 relationship in PSCI is remarkably influenced by the level SCI and physical training. PMID- 7872984 TI - [Responses of electroencephalogram to different odors]. AB - The responses of electroencephalogram (EEG) to different odors and their densities were studied on four men and two women at rest while sitting. The odors examined were citrus, floral and lavender, and their densities were 100 ppb and 200 ppb. The odors were released for ten minutes from a duct to fill the room completely. The subjective estimation indicated that citrus had a tendency to be the most comfortable odor in this study, but it was not significant. To evaluate changes of EEG, the power spectra of frequency-fluctuation of alpha wave (Fz) and the rate of alpha, beta, and beta/alpha wave (Oz, Fz) were calculated. The rate of alpha wave (Oz) in the period of giving out the citrus at 100 ppb was significantly (p < 0.05) higher than that of the lavender. The rate of beta wave (Oz) in the period of giving out the floral at 200 ppb was significantly (p < 0.05) higher than that of the lavender. The regression coefficient of the power spectra of frequency-fluctuation of alpha wave in the period of giving out the lavender at 100 ppb was significantly higher than those in the other periods of the experiment. The regression coefficient of the power spectra of frequency fluctuation of alpha wave for lavender given out at 200 ppb was significantly (p < 0.01) higher than those for the other odors given out. It seems that the regression coefficient of the power spectra of frequency-fluctuation of alpha wave can be used for the evaluation of psychophysiological responses. PMID- 7872985 TI - [Sex differences in interrelationships between percent body fat (%fat) and waist to-hip ratio (WHR) in healthy male and female adults]. AB - The purpose of the present study was to investigate sexual differences in relationships among percent body fat (%Fat), waist-to-hip ratio (WHR), waist-to stature ratio (WSR), abdominal circumference to stature ratio (ASR), body mass index (BMI) and skinfold thicknesses in healthy male and female adults. Subjects were 64 males and 65 females, aged 22-60. Body density was measured by under water weighing and by skinfold anthropometry. Mean %Fat was 15.6% in males and 23.9% in females. Mean WHR was 0.83 in males and 0.72 in females. The correlation between %Fat and WHR was not significant in females (r = -0.104) but was significant in males (r = 0.631, p < 0.001). Highly significant correlations were obtained among %Fat, WSR, ASR, BMI, and sum of eight skinfolds in both sexes. PMID- 7872986 TI - Perceived pitch of complex FM-AM tones--pitch determination process of vibrato sounds. AB - Pitch-matching experiments were conducted to clarify the pitch determination process of complex FM-AM tones which consist of components whose frequency and amplitude are simultaneously modulated. The pitch is higher when FM and AM of each component are in phase than when they are out of phase. The pitch shift induced by the phase difference between FM and AM of each component becomes larger as its relative power increases. These experimental results suggest that the pitch of complex FM-AM tones is determined as follows: A complex FM-AM tone is resolved into each FM-AM component by the auditory filter bank. The spectral pitch of each FM-AM component is determined by a loudness-weighted pitch averaging processes. The central pattern recognizer determines the pitch of complex FM-AM tones by integration of virtual pitches derived from the spectral pitches. PMID- 7872987 TI - Ease of handling and efficacy of Bricanyl Turbuhaler in Asian asthmatic children. AB - Ease of handling as well as efficacy of a new terbutaline inhalation device- Bricanyl Turbuhaler--were evaluated among eighty-six Asian children with mild to moderate asthma with a mean age of 8.7 years (range 5 to 14 years) in an open, non-comparative trial. Clinical evaluations were performed on four occasions, ie at the beginning of the run-in period, at the start of the study medication, after 2 weeks of treatment and after a total of 4 weeks of treatment. Appraisal of handling technique was performed by the investigator at the start and end of treatment. Peak expiratory flow rate (PEF) was determined at each visit. Diaries were also kept throughout this time; PEF and asthma symptom scores were recorded every morning and evening. Maximum scores for inhalation technique were achieved by 73% of patients after combined written and verbal instructions at the start of the study and 99% of patients achieved this score at the end of the 4 week treatment period with Bricanyl Turbuhaler. Assessment revealed that approximately 90% of the patients considered loading, inhalation and handling of the Turbuhaler device to be easy, and 90% considered it to be effective in affording symptom relief. Improvements in PEF and reductions in asthma symptoms were observed during the Bricanyl Turbuhaler treatment, as compared to baseline values. All patients tolerated the study medication well without any serious adverse events. We concluded that this group of Asian children were able to use this new "Turbuhaler" device of terbutaline without any difficulty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7872988 TI - The effect of immunotherapy on bronchial hyperresponsiveness in asthmatic children. AB - Bronchial hyperresponsiveness (BHR) to methacholine were evaluated in 47 asthmatic children before and after allergen-specific immunotherapy (IT) by using the forced oscillation method. Eighty-seven percent (13/16) of BHR-negative patients had good clinical response after 1-year immunotherapy while there were only 45% (14/31) in the BHR-positive asthmatic children (p < 0.02). In the BHR positive group, the relationship between clinical response and the change of nonspecific bronchial sensitivity was further analyzed. In those of good clinical response (IT responder), the tolerance dose of methacholine was significantly increased from 0.78 +/- 0.71 to 4.11 +/- 4.65 mg/ml (p < 0.05), and bronchial sensitivity increased from 1.14 +/- 1.42 U to 7.55 +/- 9.55 U (p < 0.02). In those with no clinical improvement (IT non-responder), there were no significant changes in either methacholine tolerance dose or bronchial sensitivity. With respect to other parameters, such as Grs, PD35, and SGrs, the differences between before and after immunotherapy were similar in both the IT responders and IT non responders. These results suggest that asthmatic children with different bronchial sensitivity had different responses to immunotherapy and the clinical improvement after immunotherapy is significantly related to the improvement of bronchial hyperresponsiveness. PMID- 7872989 TI - Fusion protein of Salmonella typhi flagellin as antigen for diagnosis of typhoid fever. AB - We previously established the specific 52 kDa antigen of Salmonella typhi, detected by our monoclonal antibodies, which was a flagellin protein. Comparison of the nucleotide sequences of phase-1 flagellin of Salmonella species available through GenBank database showed high homology at both ends of the genes with lower degree of homology in the middle portion which contained the antigenically variable regions. Thus, proteins from the central regions of flagellin genes should be species specific and could be used as specific antigens for the immunodiagnostic tests. In this report, recombinant protein derived from the central region of S. typhi flagellin was produced as a fusion protein with glutathione-S-transferase. This fusion protein was used as specific S. typhi antigen for the immunodiagnostic test to detect IgM antibodies in sera using enzyme-linked immunosorbent assay. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of this test were 53.5, 98.0, 91.5, 82.1 and 92.4%, respectively. PMID- 7872990 TI - Molecular cloning and expression of Salmonella paratyphi A 52 kDa specific protein gene. AB - Monoclonal antibodies (MAbs) specific to Salmonella paratyphi A have been established by our group in 1989. These MAbs were proven to be species-specific for 52 kDa protein of S. paratyphi A but the nature of this protein is unknown. However, our group have proved that the 52 kDa protein which is specific to S. typhi was flagellin. This present study has characterized the 52 kDa protein of S. paratyphi A and identified its encoded gene. The plasmid containing the specific 52 kDa antigen gene was cloned from the S. paratyphi A genome, herein designated pSKA-4. Partial nucleotide sequences from this clone was analysed by computer program and found to be phase 1-a flagellin gene of S. paratyphi A. In addition, the nucleotide sequence analysis from such clone also showed that the structural gene for phase 1 flagellin has amino acid sequences conserved at the terminal whereas the central region is variable among Salmonella spp. Therefore, the central portion of flagellin which highly polymorphic in amino acid sequences would be the most specific to S. paratyphi A, thus, should be used as specific antigen for developing specific diagnosis of S. paratyphi A infection. Using the PCR technique, an expression plasmid containing the antigen gene producing only the variable region in the central portion of flagellin from S. paratyphi A, namely pSKA-7, has been established. The recombinant protein produced by the established plasmid has a MW 33.5 kDa as detected by immunoblotting using specific MAbs. Further study by using this specific flagellin protein for immunodiagnosis of S. paratyphi A infection is being carried out in our laboratory. PMID- 7872991 TI - Immunodiagnosis of trichinellosis: efficacy of somatic antigen in early detection of human trichinellosis. AB - Crude antigens prepared from the infective stage larvae of Trichinella spiralis were used for antibody detection by indirect ELISA and Western blotting in serum samples taken from trichinellosis patients and from normal, parasite-free controls. The serum specimens were collected from acute ill, symptomatic patients on the first day of treatment (Day 0), and then two months (M2) and 4 months (M4) later. The sensitivities of the indirect ELISA and Western blotting on Day 0 were 81% and 92%, respectively. Both tests were 100% sensitive for M2 and M4 serum samples. Every serum sample from the parasite-free controls tested negative by both immunological assays, indicating 100% specificity. Crude somatic antigens can therefore be used for the early detection of human trichinellosis (acute trichinellosis). PMID- 7872992 TI - IN vitro cell-mediated immune reactions in herpes zoster patients treated with cimetidine. AB - In a double-blind placebo-control study the immunomodulating effect of cimetidine treatment for one week and placebo was investigated for cell-mediated immune reactions of 22 patients with herpes zoster (HZ). The mitogen induced leukocyte migration inhibition test (LMIT) and the in vitro proliferation of the patients' lymphocytes to exogenous IL-2 were used. Before any treatment, the mitogen induced leukocyte migration inhibition capacity (LMIC) of HZ patients was found to be significantly reduced (p < 0.02) as compared to healthy blood bank donors (controls). After one week, within the same treatment, the LMIC was significantly improved (p < 0.01). The patients' lymphoproliferative response to IL-2, before any treatment, was not significantly different from that of controls (p < 0.05). However, significantly higher values (p < 0.001) were found in patients tested 7 days after the disease onset as compared to those tested after 12 days. One-week cimetidine treatment significantly improved (p < 0.05) the lymphoproliferative response to IL-2 of initially low responders and had no effect on higher responder patients. In contrast to this, after one week of placebo treatment, a significant decrease in the patients' lymphoproliferative response to IL-2 could be observed as compared to patients' initial responses (p < 0.05) or to those of controls (p < 0.05). Although the number of cases is very small. The data suggest that after cimetidine treatment, as compared to placebo, healing from skin rash and pain was achieved in a significantly shorter time (p < 0.01). PMID- 7872993 TI - Encapsidation defectiveness of herpes simplex virus type 2 during replication at acid pH condition. AB - The maximal yield of herpes simplex virus type 2 (HSV-2) grown at pH 6.5 decreased 10(2)-10(3) fold compared to that recovered at pH 7.5. Electron microscopic observation of the infected cells maintained at these 2 pH conditions indicated that approximately equal amounts of immature virions were synthesized 6 hours after infection. However, at 18 hours post infection the majority of viruses present in the nucleus of infected cells maintained at pH 6.5 were empty or partially cored capsids with some particles enveloped and present in the cytoplasm, whereas at pH 7.5 mature virions already appeared at the cytoplasmic membrane. Analysis of viral polypeptides by radioimmunoprecipitation indicated that the synthesis of p40, a family of polypeptides closely involved in viral DNA encapsidation, was significantly impaired in infected cells maintained at pH 6.5. PMID- 7872994 TI - The inhibitory effect of methotrexate on PAF-induced neutrophil and eosinophil locomotion in asthmatic patients. AB - We have tested the effect of methotrexate (MTX) on platelet activating factor (PAF)-induced neutrophil and eosinophil locomotion, neutrophil leukotriene B4 (LTB4) generation and mononuclear cell DNA synthesis. Neutrophils from patients treated with low dose methotrexate showed reduced PAF-induced chemotactic responses (727.8 +/- 72.2/10 HPF vs 481.9 +/- 87.3/10 HPF, p < 0.05). Both MTX and the specific PAF antagonist BN-52021 significantly inhibited PAF-induced eosinophil and neutrophil locomotion in a dose-dependent manner. MTX also reduced calcium ionophore-driven LTB4 generation from the neutrophils of asthmatics (358.9 +/- 39.5 pg/10(6) cells vs 240.1 +/- 29.1 pg/10(6) cells, p < 0.05) and attenuated PHA-induced mononuclear DNA synthesis as shown by a reduction in 3H thymidine uptake and propidium iodide staining. These findings support the view that the beneficial effects of MTX in asthma may be due not only to its anti mitotic effects on the proliferation of mononuclear cells but also to direct effects on granulocyte locomotion and production of LTB4. PMID- 7872995 TI - Nebulized salbutamol (Asmasal) in Thai children with asthma: comparison of three doses. AB - Eleven moderate-to-severe asthmatic children 5-11 years of age who were in stable condition were given (randomly, double-blind) nebulized salbutamol sulfate (Asmasal) inhalation therapy at doses of 0.1, 0.2 and 0.3 mg/kg body weight on separated days. All three doses of nebulized solution resulted in clinical improvement and improvement of lung function (FEV1, FVC, PEFR and FEF25-75%). A dose of 0.3 mg/kg produced greatest improvement and longest duration of improvement in FEV1 and PEFR, but the change was statistically significant only in PEFR at 60 minutes (p < 0.05). Five children experienced mild tremors. There were no significant changes in heart rate or blood pressure at any dose. It is concluded that a nebulized solution of salbutamol sulfate at a dose of 0.1-0.3 mg/kg is useful for treatment of asthma in Thai children, with very mild side effects. PMID- 7872996 TI - Identification of tumor markers for cholangiocarcinoma and evaluation of their diagnostic potential. AB - Results obtained from studies using experimental animal model clearly showed that (1) A marker(s) for CCA does exist; 2) This marker is a glycoprotein with a molecular weight of 200 kDa; (3) It is produced and secreted in vitro by tumor cell lines; (4) It is highly immunogenic in mice and the MAb specific for this antigen is directed against the carbohydrate moiety; (5) This tumor antigen can be detected in serum and bile of tumor-bearing animals by a sandwich ELISA employing this MAb; (6) Kinetic studies show a gradual elevation of this antigen during tumor development; and (7) The elevation of this antigen can be detected at a time when no pathological changes have yet taken place, as judged by microscopic examination. Preliminary work from the human counterpart using human cholangiocarcinoma cell line showed promising results. CCA-specific antigen could be similarly identified and the MAbs produced were highly specific for this 160 kDa antigen. PMID- 7872998 TI - Pediatric residencies and the Family Medical Leave Act. PMID- 7872997 TI - Changes in serum antibodies to Opisthorchis viverrini in humans and hamsters following treatment of opisthorchiasis. PMID- 7873000 TI - Incentives to teach physical diagnosis. PMID- 7872999 TI - When students introduce themselves as doctors to patients. PMID- 7873001 TI - Evaluating factors in the selection of residents. PMID- 7873002 TI - Positive effect of physicians-in-training on patient care. PMID- 7873003 TI - Usefulness of psychosocial screening questionnaires. PMID- 7873004 TI - Educating physicians for the twenty-first century. AB - The author reviews the fundamental changes that have taken place in the U.S. health care system since 1935, predicts what that system will be like in the early part of the next century, and discusses the implications for academic medicine. Specifically, he maintains that physicians being trained today will practice within the context of large organizations, with payment for care being either by employment-based insurance or by some form of government-subsidized insurance. Care will be delivered across diffuse networks, and most physicians will be paid according to capitation or salary schemes. The role of technology will be high and will revolutionize the health care system, which will be focused on prevention and maintenance of function rather than cure. The success of the system will be measured by its cost-effectiveness and by how well it works to maintain the mental, social, and physical functions of its participants. Finally, the obligation of the physician will be not only to individual patients but also to the populations and communities from which patients come. Training physicians to meet these obligations and to function effectively in the revolutionized system will involve changes in medical education to more appropriately socialize students into the next century's medical culture. The author reviews in detail the various elements of the medical culture that must be addressed by medical education, gives examples of the kinds of changes that must be made, and describes efforts at his school to reinforce across the curriculum the population based model of clinical practice. PMID- 7873005 TI - Developing a "clinical presentation" curriculum at the University of Calgary. AB - Currently, medical curricula are structured according to disciplines, body systems, or clinical problems. Beginning in 1988, the faculty of the University of Calgary Faculty of Medicine (U of C) carefully evaluated the advantages and disadvantages of each of these models in seeking to revise their school's curriculum. However, all three models fell short of a curricular structure based on current knowledge and principles of adult learning, clinical problem solving, community demands, and curriculum management. By 1991, the U of C had formulated a strategic plan for a revised curriculum structure based on the way patients present to physicians, and implementation of this plan has begun. In creating the new curriculum, 120 clinical presentations (e.g., "loss of consciousness/syncope") were defined and each was assigned to an individual or small group of faculty for development based on faculty expertise and interest. Terminal objectives (i.e., "what to do") were defined for each presentation to describe the appropriate clinical behaviors of a graduating physician. Experts developed schemes that outlined how they differentiated one cause (i.e., disease category) from another. The underlying enabling objectives (i.e., knowledge, skills, and attitudes) for reaching the terminal objectives for each clinical presentation were assigned as departmental responsibilities. A new administrative structure evolved in which there is a partnership between a centralized multidisciplinary curriculum committee and the departments. This new competency based, clinical presentation curriculum is expected to significantly enhance students' development of clinical problem-solving skills and affirms the premise that prudent, continuous updating is essential for improving the quality of medical education. PMID- 7873006 TI - Developing key-feature problems and examinations to assess clinical decision making skills. AB - This article introduces the concept of a key feature and describes its function as the cornerstone of key-feature problems, a new problem format for the written assessment of clinical decision-making skills of medical trainees and practitioners. The rationale for using this problem format and the steps in problem and examination development--including issues of scoring and standard setting--are described. A key feature is defined as a critical step in the resolution of a clinical problem, and a key-feature problem consists of a clinical case scenario followed by questions that focus on only those critical steps. The questions can be presented to require examinees either to write in their responses or to select them from a list of options. For each question, examines can be instructed to supply or select whatever number of responses is appropriate to the clinical task being tested, and answer keys can comprise one or several responses. This problem format, with its focus on only the critical steps in problem resolution, and with its flexibility in question format and scoring keys, effectively addresses the psychometric considerations of content validity and test score reliability, and accommodates the complexity and configurations of actions often required in the resolution of clinical problems. PMID- 7873007 TI - Implementation and evaluation of a primary care preceptorship. AB - As part of overall curricular reform, the University of Michigan Medical School developed and implemented a required primary care clerkship for third-year students in July 1993. The clerkship was intended to help students develop an understanding of the principles of comprehensive health care and of disease prevention and the knowledge and skills to manage common problems in primary care. The successful implementation of the program was based on agreement across primary care specialties on a common set of goals and objectives, which were developed with the involvement of community practitioners; frequent communication with preceptors to identify problems and students at risk; active feedback to preceptors; and thorough formal and informal evaluations of students and preceptors. Students and preceptors felt the program was beneficial to them; still, the medical school must in the future address concerns about more accurately grading students, retaining preceptors, and ensuring that students be exposed to the broadest possible range of primary care patients and services. PMID- 7873008 TI - Anatomy of the clinical simulation. AB - Computer-based clinical simulations have been used in medical education for the past 25 years. During this period, the technology has evolved from mainframe computers to microcomputers to multimedia. All designers of simulations must decide which elements of reality to include explicitly in a simulated case, which to leave to the user's imagination, and when to intervene for educational purposes. Once these decisions are made, developers of simulations have many options for structuring the simulation itself. They can develop simulations with single or multiple patient encounters, with menu or natural-language requests for data, with varying levels of volunteered information about the simulated patient, with interpreted or uninterpreted clinical findings, with deterministic or probablistic evolution of the case, with various ways to give users feedback about their progress through the case, and with manual or automated creation of specific cases. Simulations derive their specific character from how these options are implemented. PMID- 7873009 TI - Insurance market reform and the cost-containment imperative. PMID- 7873010 TI - Attitudes and opinions of faculty tutors about problem-based learning. AB - BACKGROUND: There has been little systematic attention to the opinions of faculty in evaluating problem-based learning (PBL). The purpose of this report is to describe the attitudes and opinions of tutors in PBL programs about the relative merits of PBL and traditional medical education, and to examine the influences of selected variables on these attitudes. METHOD: Questionnaires containing both Likert-type and open-ended questions were sent to 1,287 faculty members who had served as PBL tutors at 22 U.S. and Canadian medical schools during the 1992-93 academic year. All schools with identifiable PBL programs (broadly defined) were included in the survey. RESULTS: The overall response rate was 69% (882 of 1,287). As a group, the respondents were experienced in both PBL and traditional curricula, with an average of 3.75 years of experience in the former and 11.41 years of experience in the latter. Regarding both their overall attitudes and their opinions about seven of nine specific areas, the respondents evaluated PBL more positively than traditional methods. This was especially evident in the ratings of student interest and enthusiasm, faculty interest and enthusiasm, the respondents' personal satisfaction, student reasoning, and preparation for clinical rotations. The two methods were judged to be approximately equally efficient for learning. Traditional methods were judged to be superior for teaching factual knowledge of basic sciences. PBL was particularly popular with faculty in PBL-track programs, with faculty in both the newest and the oldest PBL programs, and with faculty in either primary care or "nontraditional" specialties. CONCLUSION: The findings confirm and extend the picture of PBL strengths and weaknesses that can be derived from prior anecdotal program descriptions and small sample studies. Experienced faculty seem to prefer PBL in most respects, although they have some serious reservations. The present findings also agree with prior outcome studies of PBL, suggesting that the most strongly held faculty opinions may have a factual basis. PMID- 7873011 TI - Preceptors' strategies for correcting residents in an ambulatory care medicine setting: a qualitative analysis. AB - PURPOSE: To understand the interactional strategies preceptors use as they relate to and occasionally correct interns in a general internal medicine teaching clinic. METHOD: An observational, cohort study was carried out from May 1990 through May 1993 of the precepting conversations between 11 pairs of interns and faculty preceptors in the general internal medicine ambulatory care clinic of the Hospital of the University of Pennsylvania. All interactions were videotaped and transcribed. The interactions provided numerous examples of preceptors' correcting of interns. These were analyzed qualitatively by ethnographic and conversation-analytic methods. RESULTS: The strategies the preceptors used to correct the interns were complicated and quite indirect, and tended to minimize exposing the interns' errors. These strategies revealed the dilemmas inherent in being a preceptor and also the beliefs the preceptors brought to their task. The preceptors' strategies demonstrated their high regard for maintaining the interns' self-esteem and sense of responsibility, as well as the preceptors' willingness to forego, at least for the moment, correctional strategies that might have been more explicit and direct. CONCLUSION: The preceptors' general approach to correcting interns was consistent with pedagogic norms favoring discovery learning and with societal norms favoring egalitarianism and respect for individuals. This approach, however, may not be free of problems, and raises questions regarding the effects such strategies have upon the interns' capacity for accurate self-assessment, including the assessment of their own knowledge bases. PMID- 7873012 TI - Relationship between quantity of undergraduate science preparation and preclinical performance in medical school. AB - PURPOSE: The primary purpose of this study was to determine whether a relationship existed between the quantities of undergraduate science education completed by medical students and their subsequent preclinical performances in medical school. The secondary purpose of the study was to determine the nature of any relationship present and to re-verify standard predictors of preclinical performance in medical school. METHOD: This study was undertaken at Albany Medical College in conjunction with Sage Graduate School, Albany, New York. The analysis encompassed 120 systematically and 80 randomly selected medical student academic records (200 total cases) from the entering classes of 1977 through 1992. Twelve distinct variables were collected. Data transformations were completed as required, and the data subsequently standardized. Standard descriptive statistics, correlation between variables, t-tests between systematically and randomly selected groups, and factor analysis were performed on the data collected. RESULTS: It was determined that there was no significant relationship between total hours of undergraduate science completed and average preclinical performance in medical school. In addition, correlation between subdivisions of total hours of undergraduate science (total hours of chemistry, total hours of biology, total hours of math, and total hours of physics) and subdivisions of average preclinical performance (year-one preclinical performance and year-two preclinical performance) also proved to be nonsignificant. However, significant relationships between average preclinical performance and its subdivisions and other standard predictors of preclinical performance (Medical College Admission Test score and science grade-point average) were found to be in line with values in recent literature. In addition, significant relationships were found with the National Board of Medical Examiners Part I examination. Factor analysis of all variables yielded three underlying factors: medical school preclinical performance factor, undergraduate performance factor, and quantity of non-life-sciences factor. CONCLUSION: Quantity of science-based undergraduate premedical education, either in its entirety or in subdivisions, did not materially affect the performances of the selected medical school students in their preclinical years of medical school. PMID- 7873013 TI - Age and gender differences in students' preadmission qualifications and medical school performances. AB - PURPOSE: To investigate the age- and gender-related differences in matriculants' preadmission performances and in their subsequent medical school performances. METHOD: A longitudinal database was used to provide information on the 557 students in six entering classes (1984-1989) at the University of Kentucky College of Medicine. The preadmission variables were undergraduate science and cumulative grade-point averages (GPAs), Medical College Admission Test (MCAT) scores, and interview ratings. The medical school variables were GPAs for the four years of school and scores on the National Board of Medical Examiners Part I and Part II examinations. Age- and gender-related differences were analyzed by analyses of variance. To examine age differences, the students were grouped by age at matriculation: less than 23 years old, between 23 and 27, and 28 or older. RESULTS: The younger matriculants had significantly higher undergraduate GPAs than did their older peers; however, their performances on the MCAT were nearly identical. The men had higher MCAT scores than the women in all age groups, but the older women had higher undergraduate GPAs than the older men. The younger students tended to have slightly higher medical school GPAs than the older students. No age differences were found for the NBME I and II, and no gender difference was found for the NBME II; however, a modest gender difference was found for the NBME I, with the men performing better than the women. CONCLUSION: Dramatic age and gender differences were evident in the preadmission performances, while the differences in the medical school performances were much smaller. PMID- 7873014 TI - Role of clinical evaluation in academic medical centers: results of a national survey. AB - BACKGROUND: It is widely acknowledged that academic medical centers (AMCs) must be committed to appropriate resource use and to the clinical evaluation research needed to accomplish this goal. The authors report the results of a national survey and series of site visits to further elucidate the role of centralized mechanisms for evaluating clinical practice, called clinical evaluation units (CEUs). A CEU is characterized by a separate operating unit with a physician director on at least a half-time basis complemented by data analysts, information system specialists, or other technical staff. METHOD: In April 1993, the authors mailed a survey instrument to the 60 hospitals that were members of the University Hospital Consortium (UHC) and to 28 non-UHC teaching hospitals. After four follow-up mailings and telephone reminders, a 69% response rate (61 responses) was achieved. The survey instrument highlighted areas such as the environment in which the hospitals operated, the structure and organization of clinical evaluation, the process of how these activities were carried out, and the outcomes from the CEUs. RESULTS: Twenty-two respondents had centralized mechanisms that met the authors' definition of a CEU. Support for most CEUs came from hospital administrations and not from medical school deans. An alternative structure emerged from the analysis: 18 respondents indicated that they did not have CEUs but that clinical evaluation activities were integrated into the medical staff hierarchy and dispersed throughout departments that reported to a physician executive. CONCLUSION: The discipline of clinical evaluation is in its infancy in teaching institutions. Many AMCs do not have a coordinated program of clinical evaluation; others are just starting. Clinical evaluation must become integrated into medical education and hospital operations to serve as one aspect of academic medicine's response to health care reform. PMID- 7873015 TI - Mortality of young physicians in the United States, 1980-1988. AB - BACKGROUND: The obituary section of most issues of JAMA announces the death of at least one physician under the age of 40 years. The premature death of a physician is a significant loss to society. METHOD: The authors ascertained the mortality of physicians ages 25 to 39 years occurring from January 1, 1980, through December 31, 1988, from obituary listings in JAMA, and calculated mortality rates by gender and age. Death certificates were sought for all decedents listed as residing in California, Illinois, and Pennsylvania. Cause of death was investigated for this subset. RESULTS: There were 835 young-physician fatalities reported in JAMA during the study period, (an average of 93 deaths per year). The mortality rate among female doctors was 26/100,000; among male doctors it was 40/100,000. The mortality rate of young doctors was less than half that of the general population of white persons of the same age. Of the 122 deaths for which a death certificate was located, 45 (37%) were due to disease, 32 were suicides (26%), 31 were unintentional injuries (25%), and five (4%) were homicides. CONCLUSION: Young physicians enjoy a considerable mortality advantage over non physicians of similar age. If the study findings in the death certificate sample are generalizable, at least half of the deaths of young physicians are theoretically preventable (suicides, homicides, and unintentional injuries). Residency program directors should consider how their training programs may affect the likelihood of a young physician's dying from a preventable cause. PMID- 7873016 TI - Shifting students and faculty to a PBL curriculum: attitudes changed and lessons learned. AB - BACKGROUND: The University of Toronto Faculty of Medicine is implementing a new undergraduate curriculum that emphasizes active, self-directed learning. The aims of this study were to (1) evaluate shifts in students' attitudes after initial direct experience with problem-based learning (PBL), (2) describe faculty experiences, and (3) develop guidelines for further implementation of PBL. METHOD: Questionnaires were administered at the beginning of the first PBL session and at the close of the last session (five weeks later) to the 250 second year students in 1992-93 and to their 15 faculty tutors. Quantitative data were analyzed using multivariate analysis of variance and univariate tests. Open-ended questions were categorized based on common patterns that emerged. RESULTS: Of the 250 students, 196 (78%) responded to the pretest, and 207 (83%) responded to the posttest. There was a statistically significant shift in the students' perceptions from pretest to posttest in agreeing that PBL is more effective than traditional teaching methods (increasing from 38% to 52%). The students rated traditional methods as better for knowledge acquisition, whereas PBL methods were rated better for improving teamwork and doctor-patient relationships. At pretest, the most common themes concerned a perceived danger that PBL would result in knowledge gaps, reinforce the wrong information, and make inefficient use of valuable time. Perceived advantages of PBL included that it is more stimulating and enjoyable, and it teaches students how to learn rather than to memorize. At posttest, there was an increase in favorable comments by the students. Virtually all of the attitudes expressed by the students were shared by the faculty. In addition, at pretest the faculty were anxious about the perceived lack of structure in PBL. CONCLUSION: Direct experience with PBL led to more favorable attitudes among the students and faculty. Recommendations are suggested for other schools and programs seeking to implement PBL curricula. PMID- 7873018 TI - Health of young people. PMID- 7873017 TI - Smokers: why do they start--and continue? AB - Although smoking nauseates beginners, they are encouraged to persevere by various attractions such as its associations with maturity, glamour and friendship, as well as the evident pleasure it offers for those who overcome the body's initial revulsion. Once the pleasure is attained, addiction is the main reason for not stopping, especially when reinforced by easy availability, positive associations and the belief that quitting is terribly difficult. These facts, well known and used by the tobacco industry, also provide the basis for control strategies. PMID- 7873019 TI - Ultraviolet radiation. PMID- 7873020 TI - Rational drug use in Tobago. AB - Health workers in Tobago found that patients frequently failed to make proper use of the drugs prescribed to them because the treatment had not been clearly explained. Closer contact between the doctors, pharmacists and nurses would enable staff to understand the situation better and communicate more effectively with patients. PMID- 7873021 TI - Promoting rational drug use in India. PMID- 7873022 TI - Roles and approaches of nongovernmental organizations in health development. AB - The use of a systems model of rural society for analysing the roles and approaches of nongovernmental organizations (NGOs) in health development is outlined with special reference to conditions in northern Thailand. Comparisons are drawn between approaches in the fields of relief and welfare, community development, sustainable systems development, and people's movements. PMID- 7873023 TI - Sustainability: the role of NGOs. AB - Development projects supported by nongovernmental organizations (NGOs) should be judged by their contribution to the sustainability of the local system. Institutions and their respective responsibilities need to be clearly defined. Management training must be deeply rooted in local activities. Financing must include a realistic plan for meeting long-term needs. Otherwise much effort will continue to have little lasting effect. PMID- 7873024 TI - Controlling rheumatic heart disease in developing countries. AB - The streptococcal infection that leads to rheumatic heart disease, which accounts for one third to half of the cardiac admissions in developing countries, appears to spread especially rapidly in overcrowded living conditions. Rheumatic fever can be prevented by antibiotic treatment for streptococcal sore throat in children (primary prophylaxis), and its progression towards rheumatic heart disease can also be stopped by antibiotic therapy (secondary prophylaxis). At present, the most cost-effective control strategy appears to be secondary prophylaxis. PMID- 7873025 TI - Post-abortion family planning. AB - In many countries, reproductive health services do not actively include post abortion family planning services for women who are treated for complications of unsafe abortion. This greatly increases the risk of further unintended pregnancies and unsafe abortions. The authors, drawing on the recommendations of a meeting of experts, make a plea for bridging the gap and dealing more realistically with this urgent need. PMID- 7873026 TI - Psychiatrists and folk healers in Malaysia. AB - Contrasting beliefs often make cooperation between folk healers and modern doctors seem impossible. In the field of mental health, where communication is of such central importance, better mutual understanding is especially desirable. After reviewing the complexities involved, the author makes some suggestions on how the two kinds of practitioner could help each other. PMID- 7873027 TI - Doctors' continuing education in Tanzania: distance learning. AB - A distance learning programme for medical officers and their assistants at the district level has produced some valuable lessons for future activities in continuing education. Besides correspondence and study materials, face-to-face contact between students and their tutors is a particularly important ingredient, as it provides the guidance, flexibility and motivation that are essential for an effective programme. PMID- 7873028 TI - Cultural and biological diversity in medical practice. AB - Modern medicine often fails to take into account the sociocultural and biological differences between communities. The need for a more inclusive approach to health care is increasingly apparent. The authors outlines some of the salient factors to be considered and puts forward some suggestions on how to incorporate these in medical training. PMID- 7873029 TI - Which health journals are most useful? AB - Records are kept in a database of the sources cited in publications currently being received at the library of the Institute of Tropical Medicine in Antwerp in the subject areas of health services and endemic diseases in developing countries. The frequency of citations shows which journals are most useful on these two subjects. Although such an analysis necessarily reflects the needs of the institution carrying it out, it helps to form a more complete idea of what is available. PMID- 7873030 TI - Technology assessment in developing countries. AB - Although developing countries can ill afford to make the wrong choice of technology, they usually find it difficult if not impossible to support an adequate technology assessment programme. Much of the available information on the efficacy of various products is valid for other countries, but factors such as epidemiology, cost-effectiveness and acceptability also have to be taken into account, and these vary considerably from one setting to another. There is therefore a strong case for developing national programmes as quickly as possible. PMID- 7873031 TI - Is the Hippocratic Oath an anachronism? PMID- 7873032 TI - Is the Hippocratic Oath an anachronism? PMID- 7873033 TI - Changing medical education. PMID- 7873034 TI - Preparing doctors in the community. PMID- 7873035 TI - Working for community health in Pakistan. PMID- 7873036 TI - A model school health service in Nigeria. PMID- 7873037 TI - Financing health care in Ghana. AB - Attempts to recover some government health care expenses through user charges have produced less revenue than hoped. National health insurance offers an attractive alternative, but needs to include features which check cost escalation. Community involvement and traditional medicine can also help to reduce costs. PMID- 7873038 TI - Community financing for essential drugs in Nepal. AB - Local cost-sharing schemes have demonstrated that the revenues needed to supply essential drugs can be raised from the users and at the same time reduce wastage. A significant amount of resources have been made available in this way, but lack of clear operating principles and management support has prevented them from being put to good use. PMID- 7873039 TI - Breast-feeding in Swedish hospitals. PMID- 7873040 TI - Using complexity measure to characterize information transmission of human brain cortex. AB - The information transmission among various parts of the cortex are computed with the theory of mutual information from the data of the electroencephalogram (EEG) time series of normal human subjects. The intensities of these transmissions are characterized by the "complexity" measures. These measures have revealed to be sensitively related to the functional conditions of human beings. PMID- 7873041 TI - [Effects of reduced food intake on digestive flux and use of nitrogenous matter by goats]. AB - Limited feeding effects (75% of ad libitum) were studied in 3 adult dry goats. Their diet was composed of dried beet pulps (1/3 DM), dried alfalfa (1/3 DM) and hay (1/3 DM). The CP content was 11.9% DM. Rumen fermented OM was decreased by 243 g.d-1, but rumen pH and ammonia content remained the same. Rumen bacteria synthesis efficiency was decreased (-4%), but the value (151 g crude bacteria protein.kg-1 DOM) was higher than conventional values used in PDI and NRC systems. Nitrogen rumen balance (duodenal N-N intake) was lower (-1.9 g.d-1) with restricted goats. This could be related to the increase in urinary urea excretion (+0.4 gN.d-1). There was no significant effect of the limiting feeding on total OM and N digestibilities. The disappearance rate of OM in the rumen and the small intestine tended to be higher (+4 and +8%, respectively) in the restricted animals. Nitrogen retention was lower (-5.7 g.d-1) in restricted goats. Only 59 (or 56%) of the duodenal nitrogen was protein. Their digestibility in the small gut was higher (+8 pts) than NPN digestibility. A total of 86% of duodenal RNA disappeared in the small gut but less than 60% of DAPA was digested in this part. PMID- 7873042 TI - Effect of ruminal inoculation of Isotricha alone or a mixed B-type fauna in a defaunated rumen on the digestion of a hay-maize diet (70:30) in sheep. AB - Two adult sheep (75 kg live weight) fitted with rumen cannulas were defaunated by the emptying method during the first period of the experiment. They were inoculated with the genus Isotricha alone during the second period, and with a mixed ciliate population (Entodinium, Eudiplodinium, Epidinium) during the third. They were fed a diet of grass hay (840 g) and pelleted maize grains (360 g) in 8 meals per day, every 3 h. Defaunation was successful and no accidental contamination occurred during the experiment. The protozoa had no significant effect on the volume of rumen digesta, nor on the turnover of the particulate phase. The addition of Isotricha and of the mixed fauna increased the ADF digestibility of the diet but, in the same animals, lowered the in sacco degradation of wheat straw. The ruminal pool sizes of dry matter (DM), organic matter (OM), nitrogen (N), neutral detergent fibre (NDF), acid detergent fibre (ADF) and acid lignin detergent (ADL) remained unchanged after protozoa inoculations. The concentration of total volatile fatty acids (VFA) was not altered by faunation with Isotricha or a mixed fauna. The molar proportion of acetate increased at the expense of all the other VFAs (mainly propionate with the mixed fauna). Correspondingly, the proportion of methane in the rumen gases increased and that of CO2 decreased in inoculated animals. The ammonia concentration was highest in animals with a mixed fauna and lowest in those inoculated with Isotricha alone. This trend is explained in terms of the specific effect of the different genera of protozoa on nitrogen metabolism. PMID- 7873043 TI - Digestibility, blood levels of nutrients and skin responses of calves fed soyabean and lupin proteins. AB - Three milk substitute diets in which the protein was provided either by skim milk only (control diet) or mainly (71%) by a commercial soyabean or lupin concentrate (soyabean or lupin diet, respectively) were given to intact or ileo-caecal cannulated preruminant calves. In vitro tests showed that both concentrates were partially proteolysed and had low antigenic and antitryptic activities. The low antigenicity was confirmed in vivo since none of the calves produced specific plasma antibodies against dietary proteins, and skin reactions following the injection of these proteins were minor. Postprandial plasma level of triglycerides was higher with the 2 legume diets, suggesting faster abomasal emptying of fat and probably protein. Apparent faecal nitrogen digestibility was lower (P < or = 0.05) with the soyabean and lupin diets than with the control diet (0.86, 0.88 and 0.95, respectively). At the ileal level, the differences were smaller and non-significant (0.90, 0.88 and 0.92) for nitrogen, but remained significant for valine and tyrosine with the soyabean diet, and for proline, valine, methionine, leucine and lysine with the lupin diet. However, the differences were small enough to conclude that proper denaturation of soyabean and lupin proteins by processes including partial hydrolysis can suppress their antigenicity and render them very digestible. PMID- 7873044 TI - Survival and viability of fresh and frozen-thawed in vitro bovine blastocysts. AB - Three experiments were undertaken to investigate the effect of some factors on survival and viability of bovine blastocysts produced in vitro in serum-free oviduct-conditioned media. In vitro survival to freezing was higher for blastocysts appearing on days 6 and 7 than for day 8 blastocysts (67 and 50% hatching rate vs 12%). Transfer success of day 8 blastocysts to recipient heifers was 35% (9/26) calves born vs 19% (4/21) for cows. Embryo mortality occurred mainly during the peri-implantation period (between days 21 and 45) for cows compared with heifers. Calving rate after direct transfer of frozen blastocysts without dilution was 24% (4/17) compared with 31% (5/16) for control unfrozen blastocysts. PMID- 7873045 TI - Development of a mechanistic model for rumen digestion validated using the duodenal flux of amino acids. AB - A mechanistic model describing rumen digestion is presented. The model consists of 22 compartments for classical nutrients, microbes associated with either solids or fluid, and 8 amino-acid compartments. An empirical approach for volatile fatty acids production is used. Sensitivity and behavioural analysis on several parameters demonstrated the need to improve knowledge concerning certain factors. Model results on general criteria are in good agreement with observed data. Validation on 49 experimental lysine and methionine duodenal fluxes were satisfactory. A comparison between observed and predicted values of LysDi and Metdi on several feedstuffs showed good results. This model is a first step in the building of a rumen model suitable for research and application. PMID- 7873046 TI - Study of the influence of age and weaning on the contractile and metabolic characteristics of bovine muscle. AB - Weaning is an interesting period for the study of the nutritional regulation of muscle energy metabolism, since during this stage the nature of the substrates supplied to the muscle and their energy balance are profoundly changed. The aim of this study was to determine the effect of these modifications on the contractile and metabolic characteristics of bovine muscle. Two similar groups of 7 male Montbeliard calves were used with the same age and weight, and with the same energy intake. One group consisted of milk-fed calves, the other of weaned animals. The latter were progressively weaned over a period between 107 and 128 d. The average age at slaughter in the 2 groups was 170 d. Biopsy specimens of semitendinosus (ST) muscle were taken at the ages of 66 d, 94 d (before the beginning of weaning) and 136 d (at the end of weaning) to follow the evolution of muscle characteristics. Samples of longissimus thoracis (LT) muscle were taken 24 h after slaughter and used to study the changes in protein and DNA content. The proportion and area of the different types of fiber, I (slow, oxidative), IIA (fast, oxido-glycolytic), IIB (fast, glycolytic) and IIC (fast/slow, oxidoglycolytic) were measured by immunohistochemistry and image analysis. The metabolism of the muscles was determined by studying isocitrate dehydrogenase (ICDH, oxidative) and lactate dehydrogenase (LDH, glycolytic) activity. The results obtained between 2 and 6 months of life showed an overall increase in the area of the fibers (I, IIA, IIB and IIC) and a conversion of type IIA fibers into type IIB accompanied by a shift in the energy metabolism towards a glycolytic type. Weaning caused temporary stress, whose main consequences were to decrease overall muscle fiber area and the percentage of type IIB fibers, and increase the proportion of type IIC fibers in weaned animals. These effects may have been due to the nutritional and behavioral disturbances that accompany weaning, because 42 d after the end of weaning there was no difference in the size of ST and LT fibers between the 2 groups whereas the proportion of type IIA fibers was still higher in weaned animals. PMID- 7873047 TI - Comparative analysis of the polypeptide pattern of cumulus cells during maturation of porcine cumulus oocyte complexes in vivo and in vitro. AB - The protein patterns of porcine cumuli oophori matured as intact cumulus oocyte complexes either in vivo or in vitro with or without FSH and LH for 46 h were investigated. In in vivo-matured cumuli oophori, a 53 kDa band disappeared after 24 h maturation, but reappeared at 46 h. Furthermore, the production of a polypeptide with a relative molecular mass of 44,000 ceased and the appearance of 2 other proteins with relative molecular masses of 38,000 and 28,000 was observed. In cumuli oophori matured in vitro with or without addition of FSH and LH the 53 kDa band ceased after a culture period of 12 h. This band was produced again after a culture period of 46 h. In contrast, the polypeptide with the relative molecular mass of 44,000 ceased only in cumuli oophori cultures supplemented with FSH and LH, and the 2 proteins of M(r) 38,000 and 28,000 were detected only in the protein profiles of mature cumuli cultured with FSH and LH. It is concluded that the addition of FSH and LH to the culture medium is necessary for cumuli oophori to synthesize a protein pattern, which corresponds closely to that produced by cumuli oophori matured in vivo. PMID- 7873048 TI - Immersion in bovine insulin stimulates growth of tilapia. AB - The objective of this study was to investigate the effects of bovine insulin on growth responses in tilapia. Juvenile hybrid male tilapia (Oreochromis niloticus x O aurea; n = 135) were subjected to 1 of 3 treatments. Each treatment was subdivided into 3 replicates of 15 fish each. The fish were immersed into 1 of 2 doses (10 and 100 micrograms/100 ml water) of insulin or no hormone for 15 min per week for 8 weeks. Body weight, growth and feed conversion efficiency were significantly higher as a result of the first 4 weeks of insulin treatment as compared to control fish. The lower dose of insulin had a better stimulation effect than that of the higher doses. Insulin also stimulated feed consumption. Liver protein and protein/DNA ratio were higher in both insulin-treated groups than in the control group. Muscle proximate composition and hepatosomatic index were similar in the insulin-treated and control groups. The experimental findings suggest that insulin administered by immersion can enhance growth, feed consumption, food utilization and liver cell size in tilapia. PMID- 7873049 TI - Regulatory Control and Standardization of Allergenic Extracts. 7th International Paul-Ehrlich Seminar. Langen, September 7-10, 1993. PMID- 7873050 TI - Monoclonal antibody immunoassays: quantitative methods for allergen standardization. PMID- 7873052 TI - Regulation in the EEC. PMID- 7873051 TI - Value of monoclonal antibody-based assays: advantages and drawbacks. AB - Monoclonal antibodies (mAbs) directed to allergens are highly specific tools in allergen standardization and quantification. Their mono-specificity allows sensitive detection of individual allergens. It is the same quality that asks for caution. MAbs can be too specific: isoforms of allergens can be missed. On the other hand, mono-specific antibodies can also be crossreactive, possibly resulting in overestimation of allergen content. Lower affinity of mAbs compared to IgE may lead to underestimation of the IgE-binding capacity of an allergen extract. For application of mAbs these potential pitfalls should be taken into consideration. PMID- 7873054 TI - New developments in in vitro methods. Quantification of clinically relevant allergens in mass units. PMID- 7873053 TI - Peptide-induced T cell clones: specificity, MHC restriction, proliferation and cytokine pattern as a function of different stimulations. AB - CD4+ T cell clones were generated to tetanus toxin or to two tetanus toxin derived peptides p2 (AA 830-834) and p30 (AA 947-976). 11 of the 24 p30-specific clones reacted to shorter p30 subunits (p301 or p302), and only 14 of the p2 or p30-specific clones reacted with TT presented by EBV-transformed B cell lines (B LCL). The p30-specific clones were HLA-DP4 restricted. In contrast to autologous B cell lines, the majority of allogeneic, but HLA-DP4-positive cell lines failed to present p30 to the specific clones. We concluded that T cell clones are highly specific and that both, small alterations of the peptide length as well as discrete differences of the HLA-molecule may abrogate recognition of the peptide HLA complex by T cells. Moreover, use of peptides as stimulators of T cells may recruit and activate T cells which fail the "original" peptide, derived from normal antigen processing. Clones could usually be maintained in culture for 4-6 months, but with the help of freezing and thawing some clones are now available for over 2 years and still specific. Comparison of different autologous antigen presenting cells, namely B-LCL and activated MHC class II-positive T cells revealed that not all clones were able to mount a proliferative response to peptide presentation by T cells, while all clones proliferated to B cells as APC. If stimulated with peptide and B-LCL, the clone proliferating to T cells as APC (so-called T responder clones) secreted a broad spectrum of cytokines (Th0-like) and were easier to maintain in culture. In contrast, clones which were unable to proliferate to peptide presentation, so-called T-nonresponder clones, showed a more restricted cytokine pattern and elevated or very low IL4/IFN gamma ratio upon antigen specific stimulation. However, all clones secreted at least small amounts of IL2, IL4, IFN gamma and TNF alpha, if stimulated by PMA and ionomycin. Thus, both chemical and antigen-specific stimulations should be considered if T cell clones are classified as Th1 or Th2, whereby those clones, which secrete a limited cytokine pattern after antigen stimulation only, might be named Th1 or Th2 like clones, while clones which even after PMA/ionomycin do not secrete all cytokines, might represent "real" Th1 or Th2 clones. PMID- 7873055 TI - Current status of allergen-specific immunotherapy. PMID- 7873056 TI - Control of allergen preparations in Finland. Ten years of experience. PMID- 7873057 TI - Importance of standardized allergens in the diagnosis of atopy and atopic diseases. PMID- 7873058 TI - Quality control and stability of chemically and physically modified allergen extracts. PMID- 7873059 TI - Production and testing of allergenic extracts for diagnostic and therapeutic use in humans: regulatory considerations. PMID- 7873060 TI - Use of liposomes for standardized therapeutic allergens. PMID- 7873061 TI - Compliance and acceptance problems with standardized extracts. AB - In summary, there are a number of segments of the allergy community that are affected by compliance and acceptance of allergen standardization: regulators, allergen products manufacturers, allergists and allergy patients. To maximize compliance and acceptance of new products, these different groups must be considered when making decisions that impact on standardization and utilization of allergens. In closing it is essential that the following issues are addressed: Units--The number of different units currently used in the same extracts during the transition and the different units used throughout the world are particularly troublesome, both for physicians and patients that they treat. Uniform units or at least a formula to calibrate different units to an international system will go a long way in enhancing the compliance and acceptance of standardized products among those who produce them, use them and are treated by them. Cost--Cost of standardization continues to be a concern. The good news is that the new standardized extracts probably will not cost that much more than the old unstandardized extracts. However, implementation of new extracts can be expensive and we need to find ways in which we can minimize such costs to the allergy patients. Support is needed to continue allergen characterization. We need to encourage traditional sources of funds such as the NIH and manufacturers to continue to provide support for the allergen characterization and the standardization process. Commitment--Is the allergy community really committed to allergen standardization? Are regulators committed to provide the resources to develop standardized extracts? Does the allergist want to use standardized extracts? Do allergy sufferers really want standardized extracts in their treatment?(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873062 TI - Current state of allergen regulations: a manufacturer's opinion. PMID- 7873063 TI - Inhibition of IL-4- and IL-13-induced IgE synthesis by an IL-4 mutant protein. PMID- 7873064 TI - Immunoregulation in allergy: the potential of anti-IgE antibodies of IL-4 antagonists for the treatment of allergic diseases. AB - IL-4 plays a crucial role in the induction of allergic responses, not only in inducing the switch of B cells to the production of IgE antibodies but also in promoting the differentiation of T cells to the TH2 phenotype leading to the production of IL-4 and IL-5. Initially, IL-4 may be provided by basophils and/or mast cells which have been shown to produce IL-4 as a consequence of IgE receptor mediated stimulation. However, after immunization IgE+B cells may persist for a prolonged period leading to further IgE responses which are IL-4-independent. In order to achieve inhibition of IgE, independent of the nature of the allergen and independent of the state of immunization, non-anaphylactogenic anti-IgE antibodies have been generated, which were shown to inhibit IgE in vivo without inducing anaphylactic reactions. A corresponding humanized (mouse-human chimeric) anti-human IgE antibody has been generated in collaboration between Tanox Biosystems and Ciba. This antibody is now under clinical investigation for the potential treatment of allergic rhinitis. PMID- 7873065 TI - Neuroendocrine and autoimmune regulation of the allergic response. PMID- 7873066 TI - Methods used to develop standards. PMID- 7873067 TI - WHO-IUIS International Standards: advantages of these extracts. PMID- 7873068 TI - The WHO-IUIS International Reference Preparations for Allergens: drawbacks. PMID- 7873069 TI - Use of skin testing for evaluation of potency, composition, and stability of allergenic products. PMID- 7873070 TI - Regulation of allergenic products in the U.S.A.; CBER initiatives. PMID- 7873071 TI - Critical evaluation of the use of skin tests and cellular tests in standardization of allergens. AB - In two groups of 8 and 40 allergic patients repeatedly skin-tested with various dilutions of timothy allergen and with histamine (10 mg/ml) intradermally and by prick test, the skin reactions were evaluated by wheal and erythema size at 20 minutes and kinetically followed over 60 minutes by infrared telethermography. The latter technique permits to define further reaction parameters, such as thermographic area and Thermographic Units based on the average elevation of temperature in the reaction site. These studies have led to several conclusions. First, the skin area really involved in skin reactions to allergens or to histamine are much larger than assessed visually. There is more to it than meets the eye. Second, among all parameters studied in terms of reproducibility upon repeated testing, erythema and thermographic areas are the most stable, while wheal area shows considerably larger variations. Third, there is no good correlation between reactions to allergen dilutions and reactions to histamine, either individually or as groups of patients. In addition, the ratio of thermographic area (as true indication of allergic inflammation) to erythema area and the kinetics of the reaction are very different between allergen-induced and histamine-induced reactions. There is therefore no real advantage in relating reactions to allergen to reactions to histamine, in terms of biological standardization. Fourth, the intradermal technique, in terms of reactions to histamine, definitely shows better reproducibility than the prick test technique in skilled hands. A method such as the HEP standardization technique, combining prick testing, evaluation of skin reactions by wheal area and reference to a histamine standard is therefore the worst of possible alternatives. The US method, based on intradermal injection of various dilutions of allergen and evaluation of erythema, seems to us more adequate and reproducible for quantitative biological standardization of allergen extracts by skin testing. This statement does not mean that prick testing could not nevertheless be considered as a method of choice for diagnostic skin testing. PMID- 7873072 TI - [Pharmacognostic identification of the confusing drugs of Magnolia bark--the barks of four Manglietia plants]. PMID- 7873073 TI - [Medicinal plant resources of Thalictrum in Gansu Province]. AB - In this paper, the species, ecology and distribution of the medicinal plants of Thalictrum in Gansu Provinceare are reported. Eleven species and 4 varieties have been found good for medical use. Their effectiveness and chemical composition have also been discussed. PMID- 7873074 TI - [Application of potassium fertilizer for jobi]. PMID- 7873075 TI - [Soils for growth of Angelica dahurica (Fisch.) Benth. et. Hook]. PMID- 7873076 TI - [Effects of ecological environment, collecting stages and storage time on chlorogenic acid content of Lonicera ferdinandii Franch]. PMID- 7873077 TI - [Determination of alkaloids and comparison of the acute toxicity of differently processed products of the seeds of Strychnos nux-vomica L]. AB - This paper deals with the extraction, determination and identification of the alkaloids in differently processed products of the seeds of Strychnos nux-vomica. The relationship between processing methods and toxicitys is discussed according to the comparison of acute toxicity. PMID- 7873078 TI - [Quantitative analysis of geniposide in fructus Gardeniae and its different processed products]. AB - The paper reports the content determination of geniposide in Fructus Gardeniae and its different processed products by HPLC. The method is simple, accurate and reproducible, with an average recovery of 101.97%, RSD 1.01%. PMID- 7873079 TI - [Comparative study on yinqiao detoxicating decoction in new convenient and old traditional forms]. PMID- 7873080 TI - [Determination of syrigin in zengzhi granule by HPLC]. AB - On Zorbax Sil column with a mobile phase of chloroform-isooctane-methyl alcohol acetic acid (30: 13: 4: 3), the content of syrigin in Zengzhi granules was determined by HPLC at 270nm. The results show that the recovery is 102.52 +/- 1.98% and RSD 1.93%. The content of syrigin is 0.0543 +/- 0.0005mg/g. PMID- 7873081 TI - [Chemical constituents of flower of David lily]. AB - Three compounds were isolated from the flower of Lilium devidii. On the basis of chemical reaction, UV, MS, 1HNMR and 13CNMR spectral data, they were identified as beta-sitosterol, stigmasterol and emodin. These compounds are obtained from the plant for the first time. PMID- 7873082 TI - [Chemical constituents of Corydalis decumbens (Thunb.) Pers]. AB - Six compounds were isolated from the quaternary ammoruinn parts of the bulbs of Corydalis decumbenbs in Shangrao District. The structures of menisperine and ferulic acid obtained for the first time from this plant were identified. Other compounds were found identical with the literature so far reported. PMID- 7873083 TI - [Chemical studies of Epimedium acuminatum Franch]. AB - Three flavonol glycosides isolated from the aerial parts of Epimedium acuminatum were identified as baohuoside II, epimedoside A and icariin on the basis of spectral data (UV, IR, MS, and 1HNMR) and chemical properties. Baohuoside II was isolated from the species for the first time. PMID- 7873085 TI - [Single calcium channel analysis and electron spin resonance (ESR) spectral study on the myocardial effects of ginsenoside Rb2]. AB - Based on the patch clamp technique, the effect of ginsenoside Rb2 on the single channel activity of Ca2+ was observed through the single ventricular myocytes of Wistar rats. Electron spin resonance was used to measure the free radical contents of cultured cardiomyocytes. It is proved that Rb2 can inhibit the activities of single calcium channel and significantly antagonize the increase of free radical contents induced by xanthine-xanthine oxidase. PMID- 7873084 TI - [The effects of Panax quinquefolium saponin (PQS) and its monomer ginsenoside on heart]. AB - Experiments have shown that PQS (0.03-3 mg/ml) can inhibit the contractility of papillary muscle of guinea pigs, and on depolarized sample of papillary muscle with high potassium, PQS (0.03-0.3 mg/ml) can increase this contractility. Monomer saponin-Re (10 mg/kg),-Rb3 (30 mg/kg) can inhibit the hemodynamic indication of rats, but pseudogisenoside-F11 (10 mg/kg) acts the other way round. These results prove that PQS contains two components of opposite actions. PMID- 7873087 TI - [Advances in the study on the processing of Chinese herbal drugs in 1993]. PMID- 7873086 TI - [Experimental study on compatible application of heat-clearing and detoxifying drugs with blood circulation improving drugs]. AB - The article describes the effectiveness of compatible application of heat clearing and detoxifying drugs with blood circulation improving drugs to the animal model with endotoxemia and nonspecific inflammation. The compatible application reduces PGE2, endotoxin blood concentration and reduced viscosity of whole blood, decreases Evans blue extravasation volume and pes swelling percentage, increases serum cortisol content and enhances fibrinolytic activity. The experimental result shows that in most cases these two drugs work better when used in combination which implies that compatible application is more effective in detoxification, antiinflammation and inflammation recovery. PMID- 7873088 TI - Imaging variants of the liver, pancreas, and spleen. AB - The liver, spleen, and pancreas are three of the most frequently imaged intra abdominal organs. Each organ is a complex structure affected by multiple pathologic processes. However, in order to recognize the pathologic changes that affect each organ, one must have a detailed knowledge of the broad spectrum of normal variants that can be seen when imaging the upper abdomen. This review explores the wide variability in appearance of the normal liver, spleen, and pancreas during cross-sectional imaging (CT, US, and MRI), stressing a thorough understanding of normal anatomy and the affect of physiologic variants. PMID- 7873089 TI - Oral transmucosal fentanyl. Help or hindrance? PMID- 7873090 TI - Antihyperlipidaemic agents. Drug interactions of clinical significance. AB - The available antihyperlipidaemic drugs are generally safe and effective, and major systemic adverse effects are uncommon. However, because of their complex mechanisms of action, careful monitoring is required to identify and correct potential drug interactions. Bile acid sequestrants are the most difficult of these agents to administer concomitantly, because their nonspecific binding results in decreased bioavailability of a number of other drugs, including thiazide diuretics, digitalis preparations, beta-blockers, coumarin anticoagulants, thyroid hormones, fibric acid derivatives and certain oral antihyperglycaemia agents. Although the incidence is low, nicotinic acid may cause hepatic necrosis and so should not be used with drugs that adversely affect hepatic structure or function. With the HMG-CoA reductase inhibitors, relatively new agents for which clinical data are still being accumulated, the major problems appears to be rhabdomyolysis, associated with the concomitant use of cyclosporin, fibric acid derivatives or erythromycin, and mild, intermittent hepatic abnormalities that may be potentiated by other hepatotoxic drugs. Fibrates also have the potential to cause rhabdomyolysis, although generally only in combination with HMG-CoA reductase inhibitors, and are subject to binding by concomitantly administered bile acid sequestrants. The major interaction involving probucol is a possible additive effect with drugs or clinical conditions that alter the prolongation of the QTc interval, increasing the potential for polymorphic ventricular tachycardia. PMID- 7873091 TI - Drug-induced dementia. Incidence, management and prevention. AB - Drugs are a frequently cited cause of dementia. There is a paucity of data regarding the incidence of drug-induced dementia, but it has been estimated that over 10% of patients attending memory clinics have iatrogenic disease. Drugs may impair cognition indirectly via metabolic effects, such as hypoglycaemia, by alterations of immunological factors within the CNS, and by actions that interfere with synaptic transmission. Classes of drugs most frequently responsible are the benzodiazepines, antihypertensives and drugs with anticholinergic properties. Each of these classes is likely to produce a different pattern of neuropsychological deficits. Prevention of drug-induced dementia will be aided by: (i) minimising the number of drugs prescribed; (ii) using shorter-acting preparations; (iii) avoiding agents that cross the blood brain barrier where possible; (iv) evaluating renal and hepatic function regularly; and (v) briefly assessing cognitive function before treatment. PMID- 7873094 TI - Seasonal sexually dimorphic distribution of neuropeptide Y-like immunoreactive neurons in the forebrain of the lizard Podarcis hispanica. AB - Since neuropeptide Y (NPY) is involved in several sex-specific physiological and behavioral processes, a sexual dimorphic distribution is expected in forebrain areas that take part in the control of reproduction physiology and sexual behavior. This question has been studied in the lizard Podarcis hispanica by comparing the distribution of NPY-like immunoreactive cells in several forebrain areas of males and females during the season of active (spring/summer) and inactive (fall/winter) reproductive activity. Both qualitative observations and statistical analysis (analysis of variance) indicate that the number of reactive cells within two forebrain areas, the lateral septum and the periventricular preoptic nucleus, depends on the sex (P = 0.02) and season (P = 0.03) and that, in fact, intersexual differences depend on the season of the reproductive annual cycle (P = 0.046). Other areas, such as the amygdaloid nucleus sphericus, show neither sexual dimorphism (P = 0.67), nor seasonal variation in the number of reactive cells (P = 0.18), nor seasonal variation of the intersexual differences (P = 0.75). When analyzed independently, the lateral septum shows a clear sexual dimorphism in favour of females (P = 0.003) whereas the number of reactive cells in the periventricular preoptic nucleus is significantly higher (P = 0.006) in males than in females. In the case of the preoptic nucleus, this sexual dimorphism is clearly accentuated during the season of reproductive activity (P = 0.007), but this dependence is not so clear for the lateral septum (P = 0.059).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873093 TI - Clinical trials and transethnic pharmacology. AB - It is generally agreed that the advance of a global economy must be accompanied by global drug development. Thus, more intense effort, time and expense must be given to the study of overall global population, which will ultimately be exposed to the drug in development. Race and ethnicity of the ultimate drug consumer must be evaluated, and not only in broad terms. Ethnic and racial representations must be considered in clinical trials. The differences in response to drug action in various ethnic and racial groups must be evaluated to provide information for the physician in practice, who is faced with an increasingly nonhomogeneous population, and who must prescribe medications for those patients. The practising physician urgently requires international, crosscultural collaborative studies, using standardised methods applicable to different cultural settings. PMID- 7873096 TI - Immunohistochemical and neurochemical evidence for GABAA receptor heterogeneity between the hypothalamus and cortex. AB - This study examined both the function of the GABAA receptor complex and the expression of its alpha 1, alpha 2 and alpha 3 subunits within the hypothalamus as compared to that of the cerebral cortex. A large number of different GABAA receptor subunit combinations potentially exist in various brain regions which, presumably, would intimate differing receptor structure and function. Here, we present evidence that the average functional characteristics of GABAA receptors within the rat hypothalamus are considerably different from those of the cerebral cortex. We assessed two neurochemical measures of GABAA receptor function: namely, chloride-facilitation of [3H]flunitrazepam binding and GABA-mediated 36chloride uptake. [3H]Flunitrazepam binding in the rat cortex was facilitated by increasing concentrations (12.5-500 mM) of chloride, and this facilitation was responsive to 15 min restraint. Yet, hypothalamic [3H]flunitrazepam binding was not responsive to increasing chloride-concentration in either the basal or restraint conditions. Also, maximal facilitation of GABA-mediated 36chloride uptake was significantly blunted in the hypothalamus relative to cortex (7.4 +/- 0.9 versus 35.8 +/- 1.5 nmoles/mg protein, respectively). While in vitro addition of 10 microM diazepam shifted GABA-mediated 36chloride uptake curves of the cortex to the left, diazepam addition appeared to be without effect in the hypothalamus. However, the blunted maximal facilitation of GABA on hypothalamic 36chloride uptake made accurate determination of the EC50 for the diazepam potentiation difficult. In addition to these functional disparities between the regions, differences in subunit expression were also apparent. Distributions of alpha 1, alpha 2 and alpha 3 subunit immunoreactivities within cingulate, parietal and temporal cortices and 8 major hypothalamic regions were assessed. Staining of the alpha 1 subunit was prevalent throughout the hypothalamus and cortex, and dense in both regions. However, the alpha 2 and alpha 3 subunits, while of intermediate density in cortex, were of low density or absent (alpha 3) in the hypothalamus. The alpha 2-immunoreactivity was restricted to cell bodies of the arcuate nucleus, dorsomedial nucleus and overlying dorsal area and to neuropil staining of the median eminence. Thus, functional responsiveness of the GABAA receptor differs in the hypothalamus relative to the cortex and this would seem related to the presence of different receptor alpha subunits in homogenate preparations of the two regions. PMID- 7873095 TI - Immunocytochemical localization of mammalian GnRH (gonadotropin-releasing hormone) and chicken GnRH-II in the brain of the European silver eel (Anguilla anguilla L.). AB - Using specific antibodies for the two molecular forms of gonadotropin-releasing hormone (GnRH) present in the European eel, Anguilla anguilla, (mammalian GnRH, mGnRH, and chicken GnRH II, cGnRH-II), we employed immunocytochemistry to determine the distribution of these two peptides in the brain and in the pituitary. The results indicate that mGnRH and cGnRH-II are localized in different neurons: mGnRH-immunoreactive (ir) perikaria were observed in the olfactory bulbs, the junction between olfactory bulbs and telencephalon (nucleus olfactoretinalis), the telencephalon, the preoptic region and the mediobasal hypothalamus. These cell bodies are located along a continuum of ir-fibers that could be traced from the olfactory nerve to the pituitary. Mammalian GnRH-ir fibers were detected in many parts of the brain (olfactory bulbs, ventral telencephalon, hypothalamus, optic tectum, mesencephalon) and in the pituitary. Chicken GnRH-II-ir cell bodies were detected in the nucleus of the medial longitudinal fasciculus of the midbrain tegmentum, but only scattered fibers could be detected in different parts of the brain. The pituitary exhibited very few cGnRH-II-ir fibers, contrasting with an extensive mGnRH innervation. These results are in agreement with our previous data obtained in the same species using specific radioimmunoassays for mGnRH and cGnRH-II. They demonstrate a differential distribution of the two forms of GnRH in the brain of the eel, as in the brain of some other vertebrate species, and suggest differential physiological roles for the two GnRH forms in the eel. They also provide information concerning the evolution of the GnRH systems in vertebrates. PMID- 7873097 TI - Neuropeptide Y in the developing and adult brain of the South African clawed toad Xenopus laevis. AB - To get more insight into developmental aspects of neuropeptide Y (NPY)-containing neuronal structures in the brain of amphibians and their possible involvement in background adaption, we have studied immunohistochemically the distribution of this neuropeptide in embryos, larvae and adults of Xenopus laevis. Antisera against NPY revealed that already at early embryonic stages NPY immunoreactive cell bodies are present in the ventral thalamus and rhombencephalic tegmentum. Slightly later, cell bodies appear in the olfactory bulb, the basal forebrain including the lateral and medial amygdala, the preoptic area, the ventral and dorsal thalamus, the suprachiasmatic region, the anteroventral tegmental nucleus and the solitary tract area. At late embryonic stages, the NPY cell groups not only show an increase in number of cells, but also stain more intensely. Around the time of hatching, a dramatic decrease in the number of immunodetectable cells occurs, particularly in the basal forebrain and in the rhombencephalic tegmentum. At the same time, however, new cell groups appear in telencephalic pallial regions and in the torus semicircularis. By the end of the premetamorphic stages, the distribution of NPY-immunoreactive cell bodies and fibers resembles closely the pattern observed in adult Xenopus brains. When compared with the development of catecholamine systems, it is clear that the NPY neurotransmitter system develops earlier. However, the expression of NPY- and dopamine-immunoreactivity in the suprachiasmatic nucleus occurs at about the same time (around stage 40) and coincides with several other events related to background adaptation, suggesting that this nucleus plays a key role in this complex neuroendocrine mechanism. PMID- 7873099 TI - Invasion and intracellular proliferation of Salmonella within non-phagocytic cells. AB - Salmonella species penetrate (invade) and proliferate within non-phagocytic cells such as epithelial cells. These two processes are essential for Salmonella virulence and have been shown to occur in the intestinal epithelium and cultured epithelial cells. In recent years the signals that Salmonella transmits to the epithelial cell have begun to be elucidated. In this review, we summarize the most recent findings about the molecular nature of the interactions between Salmonella and epithelial cells. These studies reveal that Salmonella causes dramatic changes in the morphology of the host plasma membrane during bacterial invasion, and that this pathogen exploits other host structures such as actin filaments and lysosomes to trigger internalization and intracellular proliferation within non-phagocytic cells. PMID- 7873098 TI - Enzyme diversity in halophilic archaea. AB - The halophilic archaea display a considerable extent of enzyme diversity. The presence or absence of certain enzymatic activities is closely linked with the taxonomic status of the strains investigated. Thus, Halobacterium species such as Hb. salinarium, Hb. halobium, and Hb. cutirubrum differ from most other Halobacteriaceae tested by the possession of an NAD(+)-dependent glycerol dehydrogenase, by the absence of methylglyoxal synthase activity, and the ability of fermentative growth on arginine. Species such as Hb. saccharovorum and Hb. sodomense, which are still classified within the genus Halobacterium, have an enzymatic machinery greatly different from that of the Hb. salinarium-Hb. halobium group, confirming the need for a taxonomic reappraisal of these species. The presence of NAD(+)-dependent D-lactate dehydrogenase is characteristic of representatives of the genus Haloarcula, which possess only low activities of NAD(+)-independent L- and D-lactate dehydrogenases, if at all. Other enzymes which show considerable diversity are fructose 1,6-bisphosphate aldolase, of which two classes exist, and ribulose 1,6-bisphosphate carboxylase, which is present in a limited number of species. PMID- 7873101 TI - Incidence of motile Aeromonas spp. in foods. AB - A total of 80 food samples were purchased from local retail consumer shops and examined for the presence of motile Aeromonas spp. Of the food categories tested, poultry had the highest incidence, with 100% positive. This was followed by lamb samples, with 60% positive. Raw milk and cheese samples had very low incidence (20%). No motile Aeromonas spp. were found in pre-prepared salads. Shellfish, fish, pork and beef samples had incidences of 40%. Most of the strains isolated were Aeromonas hydrophila, and for most of the food categories, no Aeromonas caviae isolates were obtained. PMID- 7873100 TI - Chitin synthetases in Candida albicans: a review on their subcellular distribution and biological function. AB - In the light of recent genetic advances, some results regarding chitin biosynthetic activities are reviewed in this paper. Genes coding for distinct enzymes displaying chitin synthetase activities have been characterized in Saccharomyces cerevisiae as well as in other fungal species including Candida albicans. Several activities seem to exist in the cells: (i) one zymogenic, located in cytoplasmic vesicles called chitosomes, although the presence of other types of vesicles with zymogenic activity cannot be completely discarded, and (ii) plasma membrane associated activities (the active enzyme and probably two distinct pools of zymogenic activity). Possible relationships between these activities, if any, remain to be determined. These multiplicity of enzymes is not surprising taking into account that chitin biosynthesis is required during very well defined temporal and spatial events of the cell cycle. A general repair function for one of the chitin biosynthetic activities is proposed as a possible salvage mechanism to warrant cell survival after wall damage has been caused, since chitin appears to be the most suitable polymer to carry out this function due to its particular physico-chemical properties. PMID- 7873102 TI - Different responses of the marine diatom Phaeodactylum tricornutum to copper toxicity. AB - Different responses of the marine diatom Phaeodactylum tricornutum (Bohlin) to toxic copper concentrations were investigated. Besides the classical variables applied to toxicity studies in microalgae, such as growth or chlorophyll a content, other variables analyzed by flow cytometry were used. Toxic effects due to copper concentration were observed. Cell density reached in the stationary phase was reduced to 50% in cultures with 20 mg Cu/l, with respect to control cultures without copper. Cell light scatter properties (related to cell volume and intracellular granularity) and chlorophyll a fluorescence of microalgal cells were determined by flow cytometry analysis at the beginning of growth, 1 h after copper exposure, and when cultures reached the stationary phase (72 h). After 1 h of exposure to metal, no differences were observed, but when cultures reached the stationary phase, a gradual increase in the variables analyzed by flow cytometry was observed as the copper concentration increased. The increase in chlorophyll a fluorescence detected by flow cytometry was not correlated with an increase in the cell content of this photopigment, thus indicating an inhibitory effect of copper on photosystem II. PMID- 7873103 TI - Utilization of some phenolic compounds by Azotobacter chroococcum and their effect on growth and nitrogenase activity. AB - Azotobacter chroococcum MH1 was grown in a mannitol and nitrogen free medium supplemented with p-hydroxybenzoic acid, resorcinol, catechol or vanillic acid as a sole carbon source. Growth and nitrogenase activity of p-hydroxybenzoic acid were supported by 8, 6 and 4 mM of p-hydroxybenzoic acid, resorcinol and catechol, respectively. The generation time of 1.71 h in p-hydroxybenzoic acid did not differ from a generation time of 1.64 h, when grown in mannitol. The compound p-hydroxybenzoic acid was utilized rapidly. However, the decomposition of other phenolic compounds tested proceeded slowly. These results suggested that phenolic compounds released during biodegradation of plant wastes could be utilized as carbon sources for both growth and nitrogen fixation of Azotobacter chroococcum. PMID- 7873104 TI - [Infectious external otitis: etiology in the Terrassa region, culture methods, and considerations on otomycosis]. AB - The etiology of infections of the outer ear was studied in the area of Terrassa (Barcelona) over a six-year period (1987-1992). A total of 1419 samples of ear discharge were processed. Traditional culture media were used to isolate the microorganisms as well as a modified culture medium prepared by us (APA). Usual methods were used to identify the microorganisms. The results show Pseudomonas aeruginosa to be the most frequently isolated microorganism. 76.5% of the otitis studied were unimicrobial and the presence of moulds or yeast was noted in 6.9% of samples. Otomycosis (5.9%) is one of the major pathological processes of the outer ear, and Aspergillus niger is the prime causal agent. PMID- 7873105 TI - A direct membrane filter method for enumerating somatic coliphages in drinking water. AB - The application of a simple membrane filter method to enumerate specific somatic bacteriophages of Escherichia coli, using E. coli C as host strain, from drinking water samples was studied. The efficiency of the method using cellulosic membrane filters, samples pretreated with magnesium ions and Tween 80 added to agar medium host cell lawns ranged from 68.9 to over 112%, depending on the phage content of the sample. To avoid the pre-treatment of the sample with magnesium salts, electropositive-charged filters of cellulosic ester (HA-PEI and HA-Nalco) and Virosorb-1MDS filters were tested in conjunction with the simple membrane filter method. The electropositive filters showed wide bacteriophage recovery rate intervals depending on the sample treatment, ranging between 31.4 and 96.2% for ester-type filters, and a mean recovery lower than 2.2% for Virosorb filters. On the other hand, it was proved that the use of Tween 80 as an eluent improved somatic coliphage recovery rates for all the filters tested. In short, this methodology provides a rapid analysis (6-8 h) of the somatic coliphages from drinking water using the membrane filtration technique. PMID- 7873106 TI - [Application of immunologic methods to the analysis of bio-leaching bacteria]. AB - Pure cultures of Thiobacillus ferrooxidans and mixed cultures of Thiobacillus ferrooxidans and Leptospirillum ferrooxidans isolated from the Matahambre mine (Cuba) were used to fit immunodiffusion and immunoelectron microscopy to the study of iron oxidizing bacteria. The possibilities, advantages and limits of those techniques have been studied from both the identification and the serological characterization points of view. Finally, the efficiency of these methods was tested by applying them to the identification of microorganisms from acidic waters from the mine. PMID- 7873092 TI - Drug-induced taste and smell disorders. Incidence, mechanisms and management related primarily to treatment of sensory receptor dysfunction. AB - Drugs in every major pharmacological category can impair both taste and smell function and do so more commonly than presently appreciated. Impairment usually affects sensory function at a molecular level, causing 2 major behavioural changes--loss of acuity (i.e. hypogeusia and hyposmia) and/or distortion of function (i.e. dysgeusia and dysosmia). These changes can impair appetite, food intake, cause significant lifestyle changes and may require discontinuation of drug administration. Loss of acuity occurs primarily by drug inactivation of receptor function through inhibition of tastant/odorant receptor: (i) binding; (ii) Gs protein function; (iii) inositol trisphosphate function; (iv) channel (Ca++,Na++) activity; (v) other receptor inhibiting effects; or (vi) some combination of these effects. Distortions occur primarily by a drug inducing abnormal persistence of receptor activity (i.e. normal receptor inactivation does not occur) or through failure to activate: (i) various receptor kinases; (ii) Gi protein function; (iii) cytochrome P450 enzymes; or other effects which usually (iv) turn off receptor function; (v) inactivate tastant/odorant receptor binding; or (vi) some combination of these effects. Termination of drug therapy is commonly associated with termination of taste/smell dysfunction, but occasionally effects persist and require specific therapy to alleviate symptoms. Treatment primarily requires restoration of normal sensory receptor growth, development and/or function. Treatment which restores sensory acuity requires correction of steps initiating receptor and other pathology and includes zinc, theophylline, magnesium and fluoride. Treatment which inhibits sensory distortions requires reactivation of biochemical inhibition at the receptor or inactivation of inappropriate stimulus receptor binding and/or correction of other steps initiating pathology including dopaminergic antagonists, gamma-aminobutyric acid (GABA)-ergic agonists, calcium channel blockers and some orally active local anaesthetic, antiarrhythmic drugs. PMID- 7873107 TI - [Preservation of acidophilic bacteria]. PMID- 7873108 TI - The Spanish type culture collection of microorganisms (CECT). PMID- 7873109 TI - Effects of a modified dance-based exercise on cardiorespiratory fitness, psychological state and health status of persons with rheumatoid arthritis. AB - Cardiorespiratory function and exercise tolerance appear very limited in persons with rheumatoid arthritis (RA). Many studies have demonstrated that aerobic exercise training is beneficial to prevent physical deconditioning without inducing adverse effects on an individual's joints and general health. The present study was conducted to demonstrate that a dance-based exercise program is a safe and efficient activity to improve physical fitness and psychological state in persons with RA. A group of 19 persons (mean age, 49.3 +/- 13 yr) participated in a 12-wk exercise program (twice weekly), whereas 10 persons (mean age, 49.4 +/ 12 yr) served as controls. Health status, use of medication, joint pain and swelling, physical fitness, activity of daily living and psychological state were assessed at baseline, after the 12-wk training program and 6 mo after the end of the program. Exercise training induced a mean improvement of 13% in aerobic power, with the highest values reaching 40%. No significant changes were observed in joint status, even though the count of painful joints tended to decrease in the exercise group. Positive changes in depression, anxiety, fatigue and tension were observed after the 12-wk exercise program. These findings provide some evidences in favor of aerobic exercise in individuals with RA. Furthermore, it is of primary interest to note that a weight-bearing activity with limited ground impacts do not provoke short-term adverse effects on joint status. Further studies, however, are required to determine the long-term effect of weight bearing exercise on the health status of individuals with RA. PMID- 7873110 TI - Burn-associated peripheral polyneuropathy. A search for causative factors. AB - This study sought to evaluate the timing of burn-associated polyneuropathy (BAPN) and its relationship to burn severity or size. Seventeen burned subjects were studied 1 wk after thermal burns. Eleven subjects remained in the study to complete 6-wk follow-up studies. Nerve conduction studies were done on at least three nerves in two unburned limbs; results were numerically summarized by calculating Z scores for each parameter. A composite Z score, termed Ztotal, measured global nerve function. One week postburn, motor and sensory distal latencies were prolonged (mean Z, -0.72 and -0.85, respectively), motor conduction velocities slowed (mean Z, -1.31) and sensory nerve action potentials reduced in amplitude (mean Z, -0.66). Associations of Ztotal scores with total burn surface area and depth were not statistically significant. Those with severe neuropathy had higher levels of c-reactive protein (Spearman correlation, -0.624; P = 0.0129). There were no significant changes in Z scores at 6 wk. We conclude that BAPN is common after thermal injury, and the electrophysiologic manifestations of BAPN are present within the first week. Thermal injuries may induce an inflammatory cascade that results in alterations of nerve function. PMID- 7873111 TI - Measured versus predicted vertical displacement of the sacrum during gait as a tool to measure biomechanical gait performance. AB - The vertical displacement of the sacrum during walking is proposed as an estimation of the overall biomechanical performance of walking, independent of cardiopulmonary factors. Vertical sacral displacement during walking was measured using an optoelectronic motion analysis system in 10 normal volunteers at variable speeds. Oxygen consumption was simultaneously measured. The actual vertical displacement of the sacrum, when correlated with body weight, reliably predicted oxygen consumption (r2 = 0.91). The relationship between vertical sacral displacement and oxygen consumption persisted when controlling for the variables, velocity, square of velocity, cadence or stride length, each known to co-vary with cardiopulmonary performance. A mathematic model designed to predict the vertical displacement of the sacrum, based on sacral height and average stride length, was tested. The actual vertical sacral displacement correlated with predicted displacement (r = 0.94). Unilateral immobilization of each subject's knee resulted in a greater average vertical sacral displacement during gait than predicted. Comparing measured with predicted vertical sacral displacement may provide a clinically useful and specific overall assessment of biomechanical gait performance. PMID- 7873113 TI - Reliability and validity of the Frail Elderly Functional Assessment questionnaire. AB - Measuring functional activity for elderly at very low functional levels remains a challenge because many functional instruments have not been standardized in a frail elderly population. The Frail Elderly Functional Assessment questionnaire (FEFA) is a 19-item, interviewer-administered questionnaire designed to assess function in frail elderly at a very low activity level. The purpose of this study was to determine the reliability and validity of this instrument in a frail elderly population. Two groups of subjects over 65 yr old were selected to test the reliability and validity of this questionnaire. Test-retest reliability was determined by correlating the responses of 29 homebound (including nursing home bound) subjects who answered the questionnaire on two occasions 2 wk apart. To assess the validity of the FEFA, the questionnaire was administered to 23 frail, homebound (including nursing home-bound) elderly subjects who had a Mini-Mental State Examination score of > or = 18. Validity was determined by correlating patient responses to direct observations by the investigators of tasks addressed in the questionnaire. Correlation was also determined against the Katz's Activity of Daily Living index, Lawton's Instrumental Activity of Daily Living index, and the Barthel index. The reliability coefficient was 0.82. Correlation between the FEFA questionnaire and direct observation of questionnaire task performance was 0.90. Construct validity against the Katz's Activity of Daily Living, Lawton's Instrumental Activity of Daily Living, and the Barthel index showed correlations of 0.86, 0.67 and 0.91, respectively. Initial data indicate that the FEFA is a valid and reliable instrument that may be useful in assessing function in frail elderly people. PMID- 7873112 TI - Correlation of flexion contractures with upper extremity function and pain for spinal muscular atrophy and congenital myopathy patients. AB - To ascertain the patients' perception of the consequences of elbow flexion contractures and better understand the circumstances at their inception, we surveyed 405 spinal muscular atrophy and congenital myopathy patients. Diagrams of various elbow angles and questions concerning the effect of elbow contractures on daily activities were part of the survey. Of 108 completed responses, effectively a 24% response rate, 49 reported elbow flexion contractures. Thirteen of the 49 patients reported first noting them during extended periods of inactivity. Elbow flexion contractures greater than 25 degrees were intractable and were reported to hamper 17% (77 of 410) of specifically considered daily activities for the 49 subjects. Twenty-nine of the 49 (59%) subjects with contractures complained of contracture-associated hindrance of at least one daily function. Perceived contracture-associated difficulties increased significantly as a function of contracture severity. Elbow contractures were perceived to be useful by 12% of the respondents. The correlation between contracture severity and upper limb discomfort was also striking. We conclude that elbow flexion contractures are common and perceived to be associated with disability and discomfort for about one-half of spinal muscular atrophy and congenital myopathy patients. PMID- 7873114 TI - Six-minute walk by people with chronic renal failure. Assessment of effort by perceived exertion. AB - The ability to exercise among 20 people with chronic renal failure was assessed on three tests by measuring the distance walked in 6 min, heart rate change from pre-exercise to postexercise and perceived exertion. Test 1 was conducted to minimize practice effects. Ten participants received exercise coaching for 3 mo between Tests 2 and 3, and 10 individuals were in a control group. Distance walked was highly correlated on the three tests; heart rate change and perceived exertion were only slightly less consistent. Three people changed their perceived exertion by more than one point between Tests 2 and 3, and these changes obscured differences between the exercise and control groups. Exclusion of data for those who changed by more than one point equalized perceived exertion changes in the two groups and revealed a significant (P < 0.05) increase in distance in the exercise group (+21.8 m) but not in the control group (+1.5 m). The study demonstrates that, although perceived exertion ratings are intended for use in incremental exercise testing, they are also valuable for assessing consistency v change in the effort of individual participants in single-intensity testing, such as a self-paced walk. PMID- 7873115 TI - Magnetic resonance imaging of the lumbar herniated disc in pregnancy. AB - Lumbosacral pain is a significant complaint in approximately one-half of all pregnancies. In 15%, the pain can be disabling. Although the mechanical and positional stresses of pregnancy have been cited as the primary source of this discomfort, in approximately 1:10,000 cases a herniated lumbar disc (HNP) can be identified as the proximal cause of pain. A 35-yr-old G4AB3PO patient presenting at 10 wk of pregnancy with severe incapacitating lumbar radiculopathy is described. Magnetic resonance imaging, selected by the patient as a diagnostic option, demonstrated a clinically suspected large midline HNP at the L5-S1 level. In the past, visualizing the presence of a HNP during pregnancy by either computerized axial tomography scan or myelography has exposed the fetus to ionizing radiation. However, magnetic resonance imaging now permits a more detailed evaluation without similar x-ray exposure. To date, no recognized biologic effect of MRI on the developing fetus has been reported. Although the long-term effects of an magnetic resonance imaging on the developing fetus have not been conclusively evaluated, its potential for accurate diagnosis and subsequent patient management, as well as planning the delivery, appears to outweigh any recognized hazard to the developing fetus. PMID- 7873116 TI - The Uniform Data System for Medical Rehabilitation. Report of first admissions for 1993. PMID- 7873117 TI - Elbow complications after organ transplantation. Case reports. AB - Musculoskeletal abnormalities have rarely been reported after major organ transplantation. We recorded five cases of elbow complications after orthotopic liver and bilateral lung transplantation. Three patients (four elbows) developed heterotopic ossification at the elbow, leading to decreased range of motion, pain and difficulty performing self-feeding and perineal hygiene. Two patients (three elbows) had electrodiagnostic evidence of ulnar mononeuropathy at the elbow, whereas one patient had bilateral median mononeuropathies caused by compression at the level of the ligament of Struthers. Surgical resection of ectopic bone with postoperative radiation was required in two patients (two elbows), and nerve decompression was used in three patients (four elbows). Common factors noted in all patients with either heterotopic ossification or ulnar mononeuropathy at the elbow included prolonged encephalopathy and the use of wrist restraints with the presentation of symptoms occurring weeks after surgery. In the patient with bilateral median nerve entrapment, symptoms occurred immediately after surgery suggesting perioperative limb compression. Elbow complications after organ transplantation should be recognized to minimize long-term disability through preventive measures and appropriate treatment. PMID- 7873118 TI - Conceptual basis of outcome measures. AB - Because of its treatment configuration and the assumption of long-term benefit, rehabilitation has had a continuing interest in the measurement of outcomes. The utility of outcome indicators rests on their conceptual foundations, the technical development of measures and validation research. Some measures, particularly of functional status, have become increasingly sophisticated with the application of psychometric and statistical analysis techniques. Less effort has been devoted to an elaboration of their theoretical basis. A first step is an examination of the assumptions underlying outcome measures, the purpose of this article. Central to an understanding is clarification of definitions of key terms such as outcomes, independence, impairment, disability and handicap. All outcome measures must be seen as part of a social context of norms and expectations. However, most norms in rehabilitation are implied rather than explicit. The assumptions behind several common outcomes are examined with suggestions for ways to increase their utility. The ability of rehabilitation to compete in the current climate, stressing cost-effectiveness, will depend heavily on the robustness of outcome measures. PMID- 7873119 TI - Physical limitations are not required for chronic pain rehabilitation success. PMID- 7873120 TI - Barthel Index information elicited over the telephone. Is it reliable? AB - This study examined the comparability of estimates of functional status elicited through a telephone interview and a face-to-face interview. The Barthel Index, a commonly used measure to assess activities of daily living, was administered over the telephone and then again in the home to 366 individuals, up to 5 yr after their discharge from a rehabilitation hospital. One-half of the telephone interviews were performed by health professionals and the other half by trained lay interviewers; all of the home interviews were performed by health professionals. Proxy-respondents provided information for those unable to respond for themselves. The percent agreement between the scores on the telephone and on the home interview was always greater than 90%; the intraclass correlation coefficient for the telephone/home comparison was 0.89. Responses between the modes of interview were more consistent when provided by self-respondents than when provided by proxies. The telephone assessment worked well in identifying those who did not have functional disabilities; all individuals who scored 100 on the home interview, scored 95 or better on the telephone. When differences arose, they were always in those considered to have moderate to severe impairment and were most often (23 of 29 times) in the direction of higher scores, indicative of less disability, on the telephone. The results of this study suggest that, with the exception of a small subgroup of patients, functional status can be elicited reliably over the telephone by both lay persons and health professionals. PMID- 7873121 TI - Clozapine and other neuroleptic drugs antagonize the light-evoked suppression of melatonin biosynthesis in chick retina: involvement of the D4-like dopamine receptor. AB - The subtype of dopamine receptor mediating the suppressive effect of light on melatonin biosynthesis in chick retina was characterized pharmacologically. Acute exposure of animals to light during the dark phase of the light-dark cycle dramatically decreased melatonin levels and activity of serotonin N acetyltransferase (NAT; a key regulatory enzyme in melatonin biosynthetic pathway). Various antagonists of dopamine receptors were tested for their ability to block this action of light on the retinal melatonin formation. Intraocular (i. oc.) pretreatment of chicks with neuroleptic drugs--blockers of the D2-family of dopamine receptors, i.e., clotiapine, clozapine (an atypical neuroleptic with high affinity for a D4-subtype dopamine receptor), haloperidol, spiroperidol, sulpiride, and YM-09151-2, significantly antagonized the light-evoked suppression of the nighttime NAT activity of the chick retina in a dose-dependent manner. In contrast, remoxipride (a D2-selective dopamine antagonist), raclopride and (+)-UH 232 (D2/D3-dopamine receptor antagonists), as well as SCH 23390, a blocker of the D1-family of dopamine receptors, were ineffective. Clozapine, haloperidol, spiroperidol and sulpiride also potently antagonized the suppressive action of light on melatonin content of the chick retina. It is suggested that the dopamine receptor mediating the inhibitory effect of light stimulation on the nighttime melatonin biosynthesis in the retina of chick represents a D4-like subtype. PMID- 7873123 TI - Age-dependent changes in second messenger and rolipram receptor systems in the gerbil brain. AB - Age-related alterations in binding sites of major second messengers and a selective adenosine 3',5'-cyclic monophosphate (cyclic-AMP) phosphodiesterase (PDE) in the gerbil brain were analysed by receptor autoradiography. [3H]Phorbol 12,13-dibutyrate (PDBu), [3H]inositol 1,4,5-trisphosphate (IP3), [3H]forskolin, [3H]cyclic-AMP, and [3H]rolipram were used to label protein kinase C (PKC), IP3 receptor, adenylate cyclase, cyclic-AMP dependent protein kinase (PKA), and Ca2+/calmodulin-independent cyclic-AMP PDE, respectively. In middle-aged gerbils (16 months old), [3H]PDBu binding was significantly reduced in the hippocampal CA1 sector, thalamus, substantia nigra, and cerebellum, compared with young animals (1 month old). [3H]IP3 binding revealed significant elevations in the nucleus accumbens, hippocampal CA1 sector, dentate gyrus, and a significant reduction in cerebellum of middle-aged gerbils. [3H]Forskolin binding in middle aged animals was significantly increased in the nucleus accumbens and hilus of dentate gyrus, but was diminished in the substantia nigra and cerebellum. On the other hand, in middle-aged animals, [3H]cyclic-AMP binding revealed a significant elevation only in the hippocampal CA3 sector, whereas [3H]rolipram binding showed a significant reduction in the thalamus and cerebellum. Thus, the age-related alteration in these binding sites showed different patterns among various brain regions in middle-aged gerbils indicating that the binding sites of PKC, IP3, and adenylate cyclase are more markedly affected by aging than those of PKA and cyclic-AMP PDE and that the hippocampus and cerebellum are more susceptible to these aging processes than other brain regions. The findings suggest that intracellular signal transduction is affected at an early stage of senescence and this may lead to neurological deficits. PMID- 7873122 TI - Characterization of [3H]nemonapride binding to mouse brain dopamine D2 receptors assessed in vivo and ex vivo for metabolic modeling in PET studies. AB - We characterized [3H]nemonapride ([3H]NEM, [3H]YM-09151-2) binding to dopamine D2 receptors. In mice given [3H]NEM with and without sulpiride, the in vivo specific binding of the [3H]NEM to the D2 receptors in the striatum was assessed: SBin vivo-1, striatal uptake minus cerebellar uptake; and SBin vivo-2, uptake in the control mice minus uptake in the sulpiride-treated mice. Tissue homogenates were divided into cytosol and the membrane binding fraction (MB). When the MB was incubated in vitro with sulpiride, the dissociated and nondissociated fractions were defined as the ex vivospecific binding (SBex vivo) and the ex vivo nonspecific binding (NBex vivo), respectively. HPLC revealed that most of the radioactivity in the MB was [3H]NEM, whereas metabolites were found in the cytosol. In the striatum, the SBex vivo increased with time (50% of the total tissue uptake at 60 min), and was equivalent to the SBin vivo-2. The SBin vivo-1 was comparable to the MB. In the cerebral cortex and cerebellum, the SBex vivo decreased with time and the SBex vivo/free [3H]NEM ratios were smaller than those in the striatum. PMID- 7873124 TI - Trypanosoma cruzi infection in rats induced early lesion of the heart noradrenergic nerve terminals by a complement-independent mechanism. AB - The acute phase of the experimental Chagas' disease in rats induces extensive lesion of the heart sympathetic nerve terminals. Because of evidence indicating the involvement of immune reactions in neuron destruction provoked by Chagas' disease, we tested the effects of depleting the complement system by cobra venom factor upon the sympathetic denervation. The serum hemolytic activity against sensitized sheep erythrocytes ensured the efficacy of the anticomplementary treatment. Glyoxylic acid-induced histofluorescence and electron-microscopic methods allowed the study of the heart noradrenergic nerves. T. cruzi infection caused marked rarefaction of fluorescent nerve terminals at day 10 of infection and the ultrastructural study guaranteed that this rarefaction involved lesion of noradrenergic terminals. The complement depletion failed to prevent this early heart noradrenergic denervation, excluding the participation of complement mediated lysis as a main mechanism. PMID- 7873125 TI - An investigation of the origin of extracellular GABA in rat nucleus accumbens measured in vivo by microdialysis. AB - GABA transmission in the nucleus accumbens is believed to play a central role in motivational processes and the expression of psychostimulant drug action. Here we report measurements of extracellular GABA in nucleus accumbens of the rat and investigate its origin. Extracellular GABA was detected using microdialysis in combination with a novel HPLC-based assay. In the awake rat, GABA in the microdialysates (1) increased 10-fold following perfusion with 0.5 mM nipecotic acid, a GABA releasing agent and uptake blocker, (2) increased 7-fold following local perfusion with 50 mM KCl, (3) decreased 50% following perfusion with tetrodotoxin, (4) decreased 50% following perfusion with a Ca(2+(-free medium and (5) decreased 40% following perfusion with high (12.5 mM) MgCl. Finally, in the anaesthetized rat, GABA in the microdialysates decreased 50% following i.p. injection of 100 mg/kg 3-mercaptoproprionic acid, a GABA synthesis inhibitor. We conclude that GABA in microdialysates from nucleus accumbens of the rat (awake) responds appropriately to selected pharmacological agents and derives at least in part (50%) from neurones. PMID- 7873126 TI - Repeated amphetamine evokes biphasic alterations in the tyrosine hydroxylase mRNA level in the rat adrenal medulla: an in situ hybridization study. AB - In the present study we estimated the effects of single and repeated administration of d-amphetamine (5 mg/kg, i.p., twice a day for 14 days) on tyrosine hydroxylase (TH) mRNA levels in the rat adrenal medulla. In situ hybridization experiments, conducted using a [35S]d-ATP-labelled deoxyoligonucleotide probe and a densitometric analysis of autoradiograms, showed that repeated d-amphetamine moderately increased the TH mRNA level (by ca. 24%) in the adrenal medulla at 2 h after the last injection. In contrast, after 48 h the TH mRNA level was decreased (by ca. 21%). No significant changes in the TH mRNA level in the adrenal medulla were found following single administration of d amphetamine. These results suggest that repeated d-amphetamine administration leads to biphasic changes in the adrenal TH biosynthesis, which may reflect an adaptive response to chronic drug treatment. PMID- 7873127 TI - Comparison of the subregional distributions of the monoamine vesicular transporter and dopamine uptake complex in the rat striatum and changes during aging. AB - We have studied the heterogeneous distribution of the vesicular monoamine transporter, labelled with 3H dihydrotetrabenazine (3H TBZOH) and the dopamine uptake complex, labelled with 3H GBR12783 in the rat striatum. The ratio TBZOH/GBR12783 was higher in the anterior part of the striatum than in the caudal part. This discrepancy could not be explained by the contribution of serotoninergic innervation to 3H TBZOH binding, since the ratio TBZOH/citalopram was also higher in the anterior striatum than in the caudal striatum. The monoamine vesicular transporter and the dopamine uptake complex were more abundant in the lateral regions than in the regions situated near the midline. In the caudal striatum, the ventral part was richer in vesicular transporter than the dorsal part. In aged rats (30 months), a significant decrease in the density of both transporters was noticed in the middle part of the striatum. In the anterior part of the striatum, the ratio TBZOH/GBR12783 was elevated in aged rats compared to adult ones. This could participate in a functional adaptation of the partially diminished population of dopaminergic neurons during aging. PMID- 7873128 TI - Centrally-administered glycine antagonists increase locomotion in monoamine depleted mice. AB - It was shown in the present study that several structurally diverse antagonists of the glycine site of the NMDA receptor, including (R)-HA-966, L689,560, 5,7 dichlorokynurenic acid, 7-chlorokynurenic acid, and two of ZENECA's novel pyridazinoindole glycine antagonists, caused marked reversal of akinesia when administered intrastriatally to monoamine depleted mice. Coinjection of the glycine agonist D-serine antagonized this locomotor stimulation. In addition, all glycine antagonists tested did not cause significant locomotor stimulation when intrastriatally administered to normal mice. These data suggest that glycine antagonists may offer therapeutic utility in the treatment of idiopathic Parkinson's disease. PMID- 7873129 TI - Synergistic interactions between NMDA-antagonists and L-dopa on activity in MPTP treated mice. AB - Four experiments were performed to investigate whether or not coadministration of NMDA-antagonists potentiate the effect of an ineffective dose of L-Dopa on motor activity in hypoactive MPTP-treated mice. Motor activity was measured in an automated system recording both locomotion (horizontal) and rearing (vertical) activity. L-Dopa alone, at doses of 10 and 20 mg/kg, but not 5 mg/kg, expressed an anti-akinesia effect in MPTP-treated mice. The non-competitive NMDA-antagonist MK-801 (0.03, 0.1, and 0.3 mg/kg) increased by itself both locomotion (0.1 and 0.3 mg/kg) and rearing (0.03 mg/kg) in control (saline-treated) mice whereas no effect was seen in the MPTP-treated mice. Combined with 5 mg/kg L-Dopa, MK-801 (0.1 mg/kg) increased locomotion in MPTP-treated mice. There was no interaction seen between L-Dopa and MK 801 in the control mice. CGP40116 and CGP40117, the active D- and the inactive L-stereoisomer of the competitive NMDA-inhibitor CGP37849, respectively, were also administered together with 5 mg/kg L-Dopa. Both doses (0.003 and 0.03 mg/kg) of CGP40116 in contrast to CGP40117, produced anti akinesia effect in MPTP-treated mice. CGP40116 (0.0001 to 0.1 mg/kg) together with 5 mg/kg L-Dopa did not affect behaviour in control mice but produced (0.01 mg/kg CGP40116 and 5 mg/kg L-Dopa) in the MPTP-treated mice an anti-akinesia effect. Our findings indicate that the non-competitive NMDA-antagonist MK-801, at doses with reported side-effects, only increase locomotion while rearing remained unaltered in MPTP-treated mice when combined with 5 mg/kg L-Dopa. Only the active stereoisomer CGP40116 in contrast to CG40117, at doses far below reported side effects, dose-dependently modulated the anti-akinesia effect of a subthreshold dose of L-Dopa. Such data thus support the notion that this behavioural modulation was regulated via NMDA-receptors. The synergism between L-Dopa and the competitive NMDA-antagonist CGP40116 has a potential in treatment of Parkinson's disease to reduce the side-effects of doses of L-Dopa that are used today. PMID- 7873131 TI - Iodine-123-IBZM-SPECT: studies in 15 patients with pituitary tumors. AB - Single photon emission computerized tomography (SPECT) using the Iodine 123 labeled dopamine D2 receptor antagonist S(-)Iodobenzamide [S (-)IBZM] was performed in 15 patients with pituitary tumors. Among them there were five prolactinoma patients with macroadenoma and two acromegalic patients with macroadenoma. Specific binding in the area of the adenoma was only observed in one subject, a macroprolactinoma patient, who was responsive to dopaminergic treatment. None of the other patients, among them one macroprolactinoma patient responsive to dopaminergic treatment showed specific binding in the area of the tumor. IBZM-binding in the striatum was found to be significantly lower in the group of pituitary tumor patients as compared to controls. The results show that D2 receptors in pituitary adenomas can be visualized using SPECT. However, the sensitivity of IBZM-SPECT appears to be too poor to visualize PRL- and GH- secreting macroadenomas in general. PMID- 7873130 TI - Opioids and sexual behavior in the male rabbit: the role of central and peripheral opioid receptors. AB - The purpose of the present series of experiments was to analyze the effects of morphine and naloxone on sexual behavior in the male rabbit, and to evaluate the role of central and peripheral opioid receptors. Morphine was found to inhibit sex behavior in a dose dependent way. The effects were slight at 5 min postinjection. At 1 hr all aspects of sexual behavior were reduced. This effect lasted at least until 3 hrs postinjection. Subcutaneous (s.c.) injection produced effects at lower doses than intraperitoneal (i.p.) injection. Minimal effective doses were 1.25 and 5 mg/kg, respectively. Naloxone also inhibited sexual behavior. Again, s.c. administration had effects at lower doses than i.p. administration (0.25 vs 16 mg/kg). The effects of morphine were reduced but not completely antagonized by several doses of naloxone, independently of whether s.c. or i.p. administration were used. An opioid kappa agonist, bremazocine, inhibited sexual behavior at a low dose (30 micrograms/kg). It is suggested that the inhibitory effects of morphine may be mediated by the kappa receptor. A peripheral opioid antagonist, methylnaloxone, had no effects by itself and was unable to modify the effects of morphine. It is concluded that the effects of morphine are localized within the central nervous system. This is further supported by the observation that loperamide, a peripheral opiate agonist, had only marginal effects on sex behavior. PMID- 7873132 TI - Effects of clozapine on CSF homovanillic acid in spasmodic torticollis. AB - We studied the effect of the atypical neuroleptic clozapine (CLO) on homovanillic acid (HVA) in cerebrospinal fluid (CSF) in five patients with spasmocid torticollis. Lumbar puncture was performed before and on the seventh day of CLO treatment. Although an HVA elevation was to be expected because of the antidopaminergic action of CLO, statistical analysis failed to reveal any significant increase of HVA under CLO treatment. Thus significance of CSF HVA may be less important for the description of antidopaminergic action of neuroleptics than previously assumed. PMID- 7873133 TI - Lifetime risk of depression. AB - Over the past decade, major epidemiological studies have been conducted to determine the prevalence of depressive syndromes, primarily major depression or dysthymia. The highest prevalences occur in younger cohorts (18-29 years); considerably lower prevalences are found in older individuals (45 years and above), with the lowest in those aged 65 and older. Several studies have confirmed an increase in the cumulative lifetime estimates of major depression in successively younger birth cohorts during this century. At the same time, questions have been raised about the low prevalence of depression in the elderly, including the role of confounding factors (e.g. differential morbidity and response-biased memory). Standardised diagnostic assessment procedures may be insufficiently adapted for use in the elderly. It has also been recognised that a substantial number of elderly individuals suffer from clinically relevant symptoms of depression but do not meet the criteria for major depression. Future research will be required to elucidate fully the apparently changing rates of depression. PMID- 7873134 TI - Major depression, dysthymia and depressive personality disorder. AB - The separation of persistent depression into meaningful and useful subcategories, including major depression, dysthymia, recurrent brief depression, and depressive personality disorder, is the subject of much debate. Depressions can be grouped on the basis of their type and severity of symptoms, aetiology, clinical course, or their association with other psychiatric illnesses. Several investigators have conducted epidemiologic and family studies to evaluate the prevalence of depressive disorders, their diagnostic stability over time, and the amount of overlap among the disorders. Although progress has been made toward a better understanding of the different disorders, insufficient evidence exists to support the hypothesis that these disorders are separate and distinct from one another. However, preliminary data suggest that depressive personality disorder is separate from the other disorders. Additionally, several questions have been raised, particularly the extent to which differentiation between the depressive disorders, specifically major depression and dysthymia, has an impact on treatment decisions. PMID- 7873135 TI - Long-term treatment of depression. AB - Long-term treatment of depression encompasses two separate phases: relapse and recurrence prevention. Relapse prevention aims to consolidate the response to acute treatment. Some tricyclic antidepressants (TCAs) have been shown to be effective, possibly in lower than standard acute treatment doses. The selective serotonin reuptake inhibitors (SSRIs) have been shown to be effective at the same minimum effective doses used to treat acute depression, or in a lower dose as with citalopram. Recurrence prevention aims to reduce the risk of onset of a new episode of depression in patients with recurrent depression. Imipramine has been thoroughly studied in unipolar depressed patients in full therapeutic doses for up to five years and is clearly effective. Other TCAs have not been adequately tested and may not all be equally effective. The SSRIs fluoxetine, paroxetine and sertraline have also been shown to be effective in reducing the risk of new episodes of depression. PMID- 7873136 TI - Antidepressants: partial response in chronic depression. AB - Although most studies of chronic depression show significant improvements with antidepressants versus placebo, the average Hamilton Depression Rating Scale results attained in the active-treatment group range between 10 and 14, suggesting that many patients only partially responded and failed to reach premorbid levels of symptom remission. Studies on the fate of these patients suggest that they are much more vulnerable to relapse, work impairment and suicide. Thus, partial response may be one form of treatment resistance, falling between total failure of response in a minority of patients, and a tendency to relapse or recur despite adequate maintenance treatment. Further study is needed to address the problem of improving the quality of response and attempting to reduce the detrimental effects of depressive illness in terms of relapse and recurrence. PMID- 7873137 TI - Psychotherapy in the maintenance treatment of depression. AB - A review of epidemiologic and clinical data on depression suggests that psychotherapy is both an important alternative as well as a supplement to medication for the maintenance treatment of depression. Psychotherapy is an alternative for patients during periods when medication may not be suitable or feasible (e.g. pregnancy, nursing, before or during major surgery, or in the elderly). Psychotherapy also has a role in maintenance treatment in dealing with the social and interpersonal consequences or triggers of recurrent depression. Although the number of continuation or maintenance treatment trials that include psychotherapy is quite limited, the efficacy of maintenance treatment in the delay of recurrence and enhancement of social functioning is best established for interpersonal psychotherapy. There are also some results concerning cognitive and behavioural therapies for maintenance treatment of depression. PMID- 7873138 TI - Historical overview of outcome of depression. AB - Kraepelin established manic-depressive disorder on the psychiatric map as a remitting but recurrent disorder. As the concept of affective disorder became broader, its potentially chronic nature was also recognised in long-term follow up studies. However, the advent of antidepressants in the late 1950s gave rise to more therapeutic optimism, and a tendency to regard unremitting and chronic features as reflecting characterological rather than affective disorders. In the late 1970s, an era of reappraisal started, and it is now clear from long-term follow-up studies that recurrence is common and chronicity occurs, although probably in a smaller proportion than previously. The wheel has come full circle recently in Britain, as the Department of Health and the Medical Research Council have established relapse and chronicity in depression as major health service research priorities. PMID- 7873139 TI - Depression: a long-term illness. AB - The realisation that major depression is often both chronic and recurrent has slowly begun to change the way that depression is diagnosed and treated. In particular, the need for continuation and maintenance treatment is an issue that now deserves increased attention, especially with the availability of new classes of antidepressant treatments, which have excellent efficacy and more favourable side-effect profiles. Although the serious consequences of depressive disorders clearly indicate the need for effective and prompt intervention on the part of clinicians, the results of several studies indicate that patients with depression consistently receive no or low levels of antidepressant therapy. It is hoped that, through continued education of health care provides and patients about the consequences of depression, the issue of undertreatment of this serious illness will be resolved. PMID- 7873140 TI - Squamous cell carcinoma of the head and neck in the elderly. AB - OBJECTIVE: While squamous cell carcinoma of the head and neck (HNSCC) most commonly affects individuals in the fifth to seventh decades of life, it occasionally arises in older patients. Biologic and epidemiologic factors of HNSCC in elderly patients have been investigated to shed light on the process of neoplastic transformation in that population. DESIGN: The medical records of patients with new onset of HNSCC presenting between 1988 and 1993 were reviewed retrospectively. SETTING: Tertiary-care hospital-based clinic. PATIENTS: Eighty one individuals who developed HNSCC of the upper aerodigestive tract after their 75th birthday constituted the study group. A control group consisting of 102 patients who developed HNSCC between the ages of 40 and 70 years was also analyzed. MAIN OUTCOME MEASURE: Information about each individual's tobacco and ethanol exposure, family history of cancer, history of second primary cancer, treatment provided, and current disease status were derived from the medical record. The presence or absence of p53 gene mutation was tabulated for a subset of individuals in both the elderly and the middle-aged groups. RESULTS: The elderly patients had a significantly lower degree of alcohol and tobacco exposure, but a significantly higher rate of second primary cancers, especially in sites outside the upper aerodigestive tract. There was no difference in the incidence of cancer in first-degree relatives in the two groups. These findings were interpreted in light of results from our laboratory examining the incidence of p53 gene mutation in a large number of patients with HNSCC. A significantly higher percentage of tumors from the younger group contained a p53 gene mutation. Major surgery was an integral part of the treatment plan for most of the older patient group despite their advanced age. CONCLUSIONS: These findings suggest that HNSCC arising after the seventh decade of life less frequently involves a genetic change commonly found in younger patients. Heavy carcinogen exposure and p53 gene mutations are present less often in elderly individuals, whereas this group appears to be more susceptible to multiple cancers. The precise biologic factors involved in neoplastic transformation in this older population await discovery. Since aggressive therapy can be successfully tolerated by many elderly patients, an individualized approach to treatment is advocated. PMID- 7873141 TI - Cost analysis of antibiotic prophylaxis in clean head and neck surgery. AB - OBJECTIVE: This study was undertaken to assess the excess cost of hospitalization accrued to patients who develop postoperative wound infection following neck dissection in which the wound was not exposed to secretions from the upper aerodigestive tract. DESIGN: A retrospective cohort of patients who underwent "clean" neck dissection from 1976 to 1989 were evaluated. Antibiotic administration (yes or no), post-operative wound infection (yes or no), and duration and cost of hospitalization were assessed. SETTING: All surgeries were performed in a university medical center. PATIENTS: All patients underwent neck dissection in which the procedure was clean, ie, there was no exposure to secretions from the upper aerodigestive tract. MAIN OUTCOME MEASURES: Patients were assessed to determine administration of antibiotics (yes or no), development of postoperative wound infection (yes or no), and duration and cost of hospitalization. RESULTS: Wound infection developed in 10 (10%) of 99 patients who did not receive antibiotics. Of 93 patients who received perioperative antibiotics, three (3.3%) developed wound infection. This difference was not statistically significant. The type II (beta) error was greater than 0.2, suggesting that a significant difference may have been missed (false-negative) as a result of the small number of patients studied. The excess cost accrued to each patient who developed a postoperative wound infection was in excess of $36,000 (1992 dollars). The cost of administration of antibiotic prophylaxis to 100 patients is less than this amount. CONCLUSION: The decision to withhold antibiotic prophylaxis should not be made in an effort to reduce hospital costs. PMID- 7873142 TI - Chemotherapeutic management of head and neck malignancies with positron emission tomography. AB - OBJECTIVE: Antineoplastic chemotherapy in cases of nonresectable advanced malignancies of the head and neck can be very debilitating for the patient. For individual treatment planning, it is important to evaluate the early clinical effect of therapy. Morphological parameters, such as the size of the tumor and its relationship to adjacent structures, which can be determined by a number of imaging procedures, hardly reflect early therapeutic effects. Therefore, the metabolic activity of the tumor should be studied during antineoplastic therapy. DESIGN: Positron emission tomography was performed in 12 patients with metastasizing squamous cell carcinomas of the oropharynx, hypopharynx, and larynx before and after the first chemotherapeutic cycle. RESULTS: The fludeoxyglucose F 18 uptake was increased in all tumors and lymph nodes. In most lesions, an obvious response to treatment was observed after the first cycle of chemotherapy. However, differences in metabolic activity and changes in metabolism occurred during therapy. The treatment response varied in different lymph nodes in the same patient. There was a linear relation between metabolic change and growth rate during therapy, with different regression functions for tumors and lymph node metastases. CONCLUSIONS: Positron emission tomography provides absolute and comparable quantitative data on tumor metabolism before and after chemotherapy. It is therefore a useful method for observation and possible improvement of therapeutic measures in patients undergoing systemic chemotherapy. PMID- 7873143 TI - Floor of mouth carcinoma. The management of the clinically negative neck. AB - OBJECTIVES: Examine the management of the clinically negative neck and evaluate the role of elective neck dissection in patients with squamous carcinoma of the floor of the mouth. DESIGN: Retrospective analysis of a cohort of patients with squamous carcinoma of the floor of the mouth and N0 stage disease of the neck who were treated between 1973 and 1992. The mean follow-up was 6 years. PATIENTS: The cohort consisted of 129 patients. Excluded from analysis were patients without evidence of disease but less than 3 years of follow-up and those with uncertain resection margins. INTERVENTION: Resection of the floor of the mouth lesion with or without marginal mandibulectomy. Elective lymphadenectomy was performed in 26 (23%) of the 129 patients. OUTCOME MEASURE: Estimates were obtained of survival according to mode of therapy, classification of treatment modality, determinate cure, locoregional failure, salvage, and occult disease by clinical stage. RESULTS: Occult disease was detected in 23% of the patients who underwent elective neck dissection. Recurrence in the neck occurred in 36% of 103 patients who received follow-up but did not undergo elective neck dissection. The determinate survival at 3 years was 100% for patients with occult disease who underwent elective neck dissection. Overall, 96% of the patients who were treated with elective neck dissection were cured; 85% of the patients who received no initial treatment of the neck were cured; and 59% of the patients with failure in the neck were salvaged. CONCLUSIONS: A more aggressive approach to the neck with N0 disease may be warranted. Selective neck dissection allows early removal of occult metastases with acceptable morbidity. In elective dissection for clinically and histologically negative necks, the high rate of survival may result from the removal of metastatic carcinoma that was missed in the histopathologic sampling process. PMID- 7873144 TI - Production by human squamous cell carcinoma of a factor inducing activation and proliferation of immune cells. AB - OBJECTIVE: To examine supernatants (SNs) of human squamous cell carcinoma of the head and neck cell lines for soluble tumor-derived factors capable of inducing activation and proliferation of human immune cells. DESIGN: The SN of squamous cell carcinoma of the head and neck cell line PCI-50 was cultured in serum-free medium and tested for the ability to induce expression of activation antigens, proliferation, cytotoxicity against tumor cell targets and cytokine production by purified human natural killer (NK) and CD4+ T cells. RESULTS: Supernatant of PCI 50 promoted expression of the following activation markers on NK and T cells: CD25 (interleukin-2R-alpha), HLA-DR (major histocompatibility complex class II), CD54 (ICAM-1), CD71 (transferrin receptor), and CD69 (activation-inducing molecule). In addition, SN induced and significantly sustained (P < .01) proliferation of human unseparated peripheral blood lymphocytes and NK or T cells in culture. Purified human NK or T cells cultured in the presence of the SN and IL-2 (120 IU/mL) had significantly higher antitumor cytotoxicity than that mediated by NK or T cells cultured in AIM-V medium and IL-2. The SN induced cytokine (interferon gamma, tumor necrosis factor alpha, interleukin-6) production in purified NK or T cells. When the SN was fractionated by molecular weight-based filtration into fractions greater and less than 30 kd, the growth- and cytotoxicity-promoting activities were consistently detectable in the greater than 30-kd fraction. CONCLUSIONS: Culture SN of squamous cell carcinoma of the head and neck cell lines contain a soluble factor(s) capable of activating NK and CD4+ T cells and of promoting growth and antitumor cytotoxicity of these lymphocyte subsets in vitro. PMID- 7873146 TI - Management of the nasal dorsum in central facial injuries. Indications for calvarial bone grafting. AB - OBJECTIVE: To demonstrate criteria for primary calvarial bone grafting in central facial fractures. DESIGN: Retrospective, cohort study. SETTING: University of Iowa Hospitals and Clinics (Iowa City) and The Johns Hopkins Hospital (Baltimore, Md). PATIENTS: Consecutive sample of 27 patients with nasoethmoidal fractures. INTERVENTION: Preoperative and intraoperative analysis with surgical intervention. Patients with the following criterion received primal dorsal calvarial bone grafts: loss of dorsal nasal support in the upper bony and lower cartilaginous dorsum. MAIN OUTCOME MEASURE: Prevention of cicatricial soft-tissue contraction of the nose with primary bony dorsal reconstruction and/or nasal bone grafting. CONCLUSION: In certain severe cases of nasal bony and cartilaginous comminution, primary dorsal nasal calvarial bone grafts are indicated. PMID- 7873145 TI - Free-tissue transfer reconstruction of midfacial and cranio-orbito-facial defects. AB - OBJECTIVE: To review our results using free-tissue transfer to reconstruct midfacial and cranio-orbito-facial defects. DESIGN: Case series. SETTING: The University of Iowa Hospitals and Clinics, Iowa City. PATIENTS: Fourteen of 21 patients had defects that resulted from ablative oncologic surgery; six had severe mid-facial trauma; and one had Romberg's disease. INTERVENTIONS: Four latissimus dorsi, 11 rectus abdominis, three scapula, and four forearm free tissue transfer flaps were used. MAIN OUTCOME MEASURES: Adequate flap separation of vital structures (intracranial contents and carotid artery) from the sinonasal or oropharyngeal cavities; restoration of palatal competence, oral diet, and speech intelligibility; maxillary dental rehabilitation; aesthetic results; complications; and the patient's return to social activities outside the home after surgery. RESULTS: The intracranial contents (six cases) or carotid artery (four cases) were protected from sinonasal or oropharyngeal contamination by the reconstructive flap in all cases in which this was required. Functional closure of the palate with the flap or a prosthesis was possible in 12 of the 13 patients with a palatal defect; seven of these 13 patients have had full maxillary dental rehabilitation. Twenty patients take an oral diet. Sixteen patients have normal or easily understood speech. Fourteen patients engage in social activities outside the home, and eight have returned to full-time employment. No vascular flap failures occurred in this series. CONCLUSIONS: The use of free-tissue transfer flaps is a safe and effective technique for repairing large midfacial and cranio-orbito-facial defects resulting from ablative oncologic surgery or trauma. PMID- 7873147 TI - Five-year follow-up of nonsecreting pituitary adenomas. AB - Nowadays, nonsecreting pituitary adenomas are usually operated on by means of a transsphenoidal approach, and the transseptal way is the most widely used. Since 1982 we have been using lateral rhinotomy instead, resecting bone in the piriform aperture up to the orbit to obtain a good intrasellar view during surgery. In all, 48 patients were operated on between 1982 and 1987, and all of them have since been evaluated in a 5-year follow-up. The only recurrence occurred in the only patient previously operated on transcranially. Computed tomography was performed in 44 patients (92%) after an average of 4 years and revealed no signs of tumor in any of them. New pituitary insufficiencies developed in six (12%). An improvement in vision was observed in 38 patients (79%), none of whom suffered an impaired visual field or acuity. The frequency of new hormonal insufficiencies and improvement of vision that we observed in our patients is comparable with that reported by other investigators, but the recurrence rate is lower and the optic nerves and chiasma were never damaged thereby causing an impairment of vision. These benefits can most probably be explained by the surgical approach we used, in which the tumor and surrounding structures are very well visualized because the operative field is broader and closer than it is with the transseptal approach, which is normally used for this kind of tumor. PMID- 7873148 TI - Long-term nasal mucosal tissue expansion use in repair of large nasoseptal perforations. AB - Reperforation rates of large, surgically closed nasoseptal perforations remain unacceptably high (30% to 70%). With the advent of newer surgical techniques, including external decortication rhinoplasty and midface degloving, excellent exposure of the intranasal anatomy is afforded. The limiting factor of these approaches is the deficiency of local intranasal mucosal lining, which is used to close large septal perforations. The paucity of nasal mucosal lining results in excessive tension on the perforation closure suture line that leads to distal flap ischemia, anastomosis breakdown and, ultimately, reperforation of the septum. Alternatively, using intraoral mucosal flaps of sufficient length and width to close large perforations results in significant and unacceptable donor site morbidity. We present our technique of harvesting additional local endonasal mucosa using long-term soft-tissue expanders. Long-term nasal mucosal expansion was used in the closure of large septal perforations in five patients. Complications included one case of expander exposure and the morbidity of prefacial expander injections. Total closure of all five septal perforations was documented at the 1-year postsurgical visit. Histologic and electron-microscopic examinations of the expanded nasal floor mucosa are presented. PMID- 7873149 TI - Diagnosis and treatment of obstructive sleep apnea of the larynx. AB - To determine the mechanism for obstructive sleep apnea in two patients with clinical abnormalities of laryngeal function, airflow dynamics during sleep were analyzed. The site of airway obstruction was assessed by examining pressure gradients across specific airway segments. The relation between maximal inspiratory airflow and nasal pressure was analyzed to determine (1) the critical pressure, a measure of the collapsibility of the laryngeal airway, and (2) the effect of nasal continuous positive airway pressure on airflow during sleep. Large inspiratory pressure gradients developed during sleep between the supraglottic and pleural spaces, indicating that collapse had occurred in the larynx. Elevated critical pressures of -6.4 and +1.2 cm H2O, respectively, occurred in the two patients. When the nasal pressure was raised to 10 cm H2O, normal levels of tidal airflow occurred, and obstructive apneas were eliminated. These findings indicate that sleep apnea was caused by laryngeal airflow obstruction that resulted from elevations in the collapsibility of the larynx. The response to nasal continuous positive airway pressure suggested that laryngeal sleep apnea was similar to pharyngeal sleep apnea in pathophysiologic characteristic and response to treatment. PMID- 7873150 TI - Adenoma of the middle ear. AB - Adenomas, although the most common benign tumors in the middle ear, are of low incidence. They may arise in a previously normal adult ear, causing a conductive deafness and later an aural discharge. Histologic definition may be difficult in these tumors, which are assumed to arise from middle ear epithelium. Fairly extensive surgery may be required for their eradication. Two cases are described. PMID- 7873151 TI - Imaging quiz case 1. Idiopathic, unilateral vocal cord paralysis (VCP). PMID- 7873152 TI - Imaging quiz case 2. Intraosseous cavernous-type hemangioma of the petrous temporal bone. PMID- 7873153 TI - Nose aerodynamics. PMID- 7873154 TI - Possible implications of neck lymphovenous shunts. PMID- 7873155 TI - Anesthesia of the tympanic membrane. PMID- 7873156 TI - Estrogen prevention of recurrent epistaxis. PMID- 7873157 TI - The use of silly putty as an ear plug. PMID- 7873158 TI - Assessment of thermoregulatory and postprandial thermogenesis over the first 24 hours after birth in pigs. AB - Heat production was continuously measured from birth to 24 h after birth in pigs tube-fed 14 g kg-1 of colostrum or water (sham-fed animals) at hourly intervals, and maintained at thermoneutrality (34 degrees C) or in moderate cold (24 degrees C). Results indicate that colostrum was necessary to initiate and sustain the postnatal rise in metabolic rate observed at 34 degrees C. It provided about 75% of the energy required for heat production at 24 degrees C. Heat production was increased by 74% in the cold and decreased by 30% during starvation. In both cases, maintenance of the energy balance was achieved with a compensatory drop in body temperature. At 34 degrees C, variations in postmeal heat production represented 12% of the total 24 h energy expenditure and were almost equally due to the thermogenic effect of colostrum and to confounding factors, including physical activity. In the cold, calculated postmeal thermogenesis accounted only for 3% of 24 h energy expenditure and for 9% of the extra heat produced in the cold. Our results highlight the main role of colostral energy in the energy metabolism of the newborn pig in a typical birth environment (24 degrees C) and in thermoneutral conditions (34 degrees C). Thermoneutral postmeal thermogenesis is low and its contribution to the extra heat produced in the cold very limited. PMID- 7873159 TI - Modulation of blood flow and tissue perfusion by endothelium-derived relaxing factor. PMID- 7873160 TI - Micropuncture and cannulation studies of fluid composition and transport in the ductuli efferentes testis of the rat: comparisons with the homologous metanephric proximal tubule. AB - Luminal fluids were collected in vivo by micropuncture and cannulation from the rete testis, efferent ducts and ductus epididymidis of the rat to determine the composition of efferent duct fluids and the rates of reabsorption of water and solutes by the efferent ducts. The concentration of spermatozoa increased by a factor of about 25 from 2.42 x 10(4) microliters-1 in the fluid from the rete testis to 6.00 x 10(5) microliters-1 in fluid at the end of the efferent ducts, indicating that 96.2% of the fluid leaving the testis is reabsorbed from the lumen of the efferent ducts. Most of this reabsorption (70.9% or 33.4 microliters h-1) occurs in the region between the rete testis and the middle of the coni vasculosi, with only 25.1% (11.8 microliters h-1) occurring between the coni and the beginning of the ductus epididymidis. However, reabsorption across the epithelium occurs at about the same rate in both regions, with the proximal region reabsorbing 17.2 microliters cm-2 h-1 (70.9% of fluid entering the region) and the distal region reabsorbing 12.2 microliters cm-2 h-1 (86.1% of fluid entering the region). Consequently, the fluid reabsorption rate for the whole efferent duct system (15.6 microliters cm-2 h-1) is similar to the values for individual regions. The principal solutes in luminal fluids from the efferent ducts are Na+ (137-144 mM) and Cl- (113-130 mM). The estimated sum contribution of Na+, Cl- and K+ to the osmotic pressure of luminal fluids was approximately 80% at each site sampled in the efferent ducts. The osmotic pressure of luminal fluid samples (301-307 mosmol kg-1) did not vary significantly along the ducts or differ significantly from that of blood plasma. The results demonstrate that there is a net reabsorption in the efferent ducts of nearly all the testicular output of water and inorganic electrolytes, and most of the protein, and that, in comparison, the ductus epididymidis is a negligible site of net fluid reabsorption. The results indicate that the ductus epididymidis, rather than the efferent ducts, is the site of accumulation of high concentrations of specific organic compounds like inositol. The efferent ducts are similar to the homologous proximal tubules of the metanephric kidney in that the luminal electrolyte composition (principal solutes Na+ and Cl-) and osmotic pressure remain relatively stable and that fluid reabsorption is close to isotonic and occurs at the same rate as the reabsorption of Na+. PMID- 7873161 TI - The role of the sarcoplasmic reticulum in the response of isolated ferret cardiac muscle to beta-adrenergic stimulation. AB - beta-Adrenergic stimulation of cardiac muscle leads to an increase in the strength of contraction and an abbreviation of its time course. We have investigated the role of the sarcoplasmic reticulum in these changes by monitoring force and cytoplasmic [Ca2+] in ferret papillary muscles, and the Ca2+ current in isolated ferret myocytes, during the application of isoprenaline in the absence and presence of the sarcoplasmic reticulum inhibitor ryanodine (10( 6) mol/l). Isoprenaline (10(-6) mol/l) led to a marked increase in the size of both the twitch and Ca2+ transient, and a decrease in their duration. In the presence of ryanodine, application of isoprenaline had no significant effect on either the size or the time course of the twitch. However, the increase in the Ca2+ current in response to isoprenaline was the same in the absence and presence of ryanodine. Increasing bathing [Ca2+] led to a prolongation of both the twitch and the Ca2+ transient. In the presence of ryanodine, increasing bathing [Ca2+] still increased the size, but decreased the duration, of the twitch. These data provide direct evidence that both the inotropic and lusitropic effects of isoprenaline are mediated via the sarcoplasmic reticulum. PMID- 7873163 TI - Haemodynamic responses to hypotensive haemorrhage in conscious sheep with emphasis on renal and femoral blood flow. AB - Haemodynamic responses to slow (0.7 ml kg-1 min-1) haemorrhage were investigated in eight adult conscious sheep, fitted with permanent ultrasonic flow probes around the renal and femoral artery. The haemorrhage was continued until the mean systemic arterial pressure (MSAP) suddenly dropped to about 50 mmHg. The spontaneous recovery was followed for 60 min and then the blood was retransfused. A distinct fall in MSAP was obtained after 14.5 +/- 0.9 ml blood (kg body weight) 1 (24% of the estimated blood volume) had been removed, but the interindividual differences were rather large (range, 10.2-18.1 ml kg-1). Therefore, the haemodynamic responses during haemorrhage were related to the total bleeding volume and not to time or volume per kilogram body weight. Before 90% of the total haemorrhage volume had been removed, the MSAP decreased gradually, reaching statistical significance at 80% (P < 0.05). At end of bleeding the cardiac output (CO) had fallen from a pre-haemorrhage level of 4.7 +/- 0.2 to 2.9 +/- 0.2 1 min 1. Although the femoral blood flow (FBF) was largely unaffected by the haemorrhage, and thus increased as a fraction of CO, the total systemic vascular resistance was markedly increased during the post-haemorrhage period, indicating a longer lasting elevation of vascular resistance in other vascular beds. In spite of a concomitant marginal decrease in renal blood flow (RBF), the renal vascular resistance (RVR) was unchanged until 90% total haemorrhage had occurred. At the same time as blood pressure fell, RBF decreased markedly, concomitant with a transient increase in RVR, which was followed by a decrease towards basal levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873162 TI - Mechanosensitive fibroblasts in the sino-atrial node region of rat heart: interaction with cardiomyocytes and possible role. AB - The positive chronotropic response of the heart to stretch of the right atrium is one of the major mechanisms adjusting the heart rate to variations in venous return on a beat-by-beat basis. The precise pathway of this mechano-electric feedback and its cellular basis are uncertain. In this study, a possible contribution of mechanosensitive fibroblasts, abundant in the sino-atrial node region, was investigated using a mathematical model of the electrical interaction of a mechanosensitive fibroblast and a sino-atrial pacemaker cell. Electrophysiological evidence for a bio-electrical interaction of mechanosensitive fibroblasts with surrounding cardiomyocytes has been studied in (i) the isolated spontaneously beating atrium of rat hearts, and (ii) cell cultures of the neonatal rat heart. These investigations were performed using (i) double-barrelled floating microelectrodes for intracellular potential registrations, and (ii) the double whole cell patch-clamp technique. It was shown that cardiac fibroblasts and surrounding cardiomyocytes can be either electrically well isolated from each other, or coupled both capacitively and electrotonically. The electrophysiological data obtained were incorporated into the OXSOFT HEART program. Assuming that equivalent coupling may occur between mechanosensitive fibroblasts and sino-atrial pacemaker cells, a heterologous cell pair consisting of one fibroblast and one sino-atrial node myocyte connected by ten to thirty single gap junctional channels with a conductance of 30 pS was modelled. The model of the electrotonic interaction of these cells showed that stretch of the fibroblast during atrial diastole, simulating increased atrial wall tension during atrial filling, can raise the spontaneous depolarization rate of the pacemaker cell in a stretch-dependent manner by up to 24%. These results show that cardiac mechanosensitive fibroblasts could form a cellular basis for the positive chronotropic response of the heart to stretch of the right atrium. PMID- 7873164 TI - Defensive reflexes of the respiratory system in anaesthetized rabbits during high frequency jet ventilation. AB - The defensive airway reflexes during high frequency jet ventilation (HFJV) were studied in anaesthetized, non-vagotomized (n = 16) and vagotomized (n = 11) rabbits. The animals were ventilated by a high frequency jet ventilator. Sneezing and coughing were evoked by mechanical stimulation of the airways. During HFJV spontaneous breathing was inhibited only in the non-vagotomized rabbits. Mechanical stimulation of the airways during HFJV evoked sneezing and coughing, in which the inspiratory component was inhibited. This inhibition occurred not only in defensive reflexes evoked from the regions with increased pressure (trachea, bronchi), but also from the nose. Vagotomy diminished but did not fully eliminate the changes in sneezing accompanying HFJV. The intensity of maximum expiratory efforts was not significantly affected by HFJV in both subgroups. PMID- 7873165 TI - Estimation of intracellular calcium activity in confluent monolayers of primary cultures of quail medullary bone osteoclasts. AB - The present study was concerned with an investigation of the relative utilities of the fluorescent indicators fura-2 and fluo-3 for spectrofluorimetric estimation of the intracellular calcium concentration ([Ca2+]i) in confluent osteoclast monolayers that had been isolated from medullary bone of quail hens and maintained in tissue culture for 6-8 days. Additionally, we have determined the effects of raised extracellular calcium ([Ca2+]o) and chicken calcitonin (CT) on [Ca2+]i in this preparation. Relative to fura-2, fluo-3 was poorly incorporated into the osteoclasts and had a high apparent equilibrium binding constant (Kd) for Ca2+ binding (809 nM). The osteoclasts were only weakly sensitive to the calcium ionophore, ionomycin. It is concluded that fura-2 is of greater utility than furo-3 in this preparation. In contrast to its lack of effect in freshly isolated cells, elevated [Ca2+]o up to 20 mM stimulated a concentration-dependent increase in [Ca2+]i in cultured osteoclasts, but CT was without effect. These findings further support the idea that quail osteoclasts are able to acquire a Ca2+ sensor or 'receptor' and thus to respond to [Ca2+]o in a similar manner to mammalian osteoclasts when they are removed from the bone microenvironment, but retain a refractoriness to CT under these conditions. PMID- 7873166 TI - Effects of hyposmotic shock on taurine transport in isolated trout hepatocytes. AB - Isolated trout hepatocytes exposed to hypotonic medium undergo a regulatory volume decrease (RVD) that occurs via two separate routes, K(+)-Cl- cotransport and amino acid release, the ion efflux accounting for 70% of the total osmolyte loss. Taurine, glutamine and glutamic acid are the most important and represent 73% of the total amino acid content (53 mmol (l cell water)-1). The osmolarity sensitive release of amino acids was studied using [3H]taurine. Kinetic studies indicated two components for taurine influx: a linear Na(+)-independent transport and a saturable Na(+)-dependent system with a Michaelis-Menten constant (Km) of 122 microM and a maximum velocity (Vmax) of 31.2 pmol (mg protein)-1 min-1. This second way of uptake was also chloride dependent and indicated an apparent coupling ratio Na+:Cl-:taurine of 2:1:1. The latter component and the taurine efflux were stimulated during RVD, leading to intracellular amino acid loss. Taurine efflux activation during volume recovery was transient and also dependent on the presence of both Na+ and Cl- in the extracellular medium. Furthermore, taurine release and RVD were slowed down when Ca2+ was omitted from the medium. These results suggested two distinct and complementary mechanisms for volume regulation in trout hepatocytes during hypotonic conditions. PMID- 7873167 TI - Modulation of K(+)-Cl- cotransport in equine red blood cells. AB - Potassium transport was measured in equine red blood cells, using 86Rb+ influx as a convenient assay. A significant component of volume- and pH-sensitive K(+)-Cl- cotransport to the overall K+ flux was observed in all blood samples studied, although fluxes were variable between animals, and within individuals when measured at intervals over a period of weeks. The aryloxyacetic acid [(dihydroindenyl)oxy]alkanoic acid (DIOA), at a final concentration of 100 microM, inhibited most (> 95%) of the Cl(-)-dependent K+ flux, and DIOA sensitivity was therefore used to define the activity of the K(+)-Cl- cotransport. K(+)-Cl- cotransport was also sensitive to protein phosphatase inhibition with calyculin A or okadaic acid, with inhibition constants of 9 +/- 1 nM for calyculin and about 100 nM for okadaic acid. Peak fluxes were observed at an external pH of 6.7-7.0, with inhibition at higher and lower values. Volume sensitive K+ fluxes assayed in autologous plasma, controlled for osmolaity, pH and potassium concentration, were significantly lower (28 +/- 8% of control values, n = 6) than those measured in saline. This inhibition was mimicked by the culture medium RPMI, but disappeared following dialysis of the plasma. Phosphate (5.6 mM) inhibited volume-sensitive K+ fluxes by 48 +/- 2%, n = 3; no significant effect was observed by increasing external magnesium concentrations to 0.5 or 2 mM. Thus, inhibition by RPMI, but not that by plasma, may be due to phosphate. Finally, volume- and pH-sensitive K+ fluxes were sensitive to oxygen tension and were abolished reversibly by equilibrating solutions with nitrogen, as opposed to air. Use of solutions equilibrated with different values of Po2 may account for some of the variability in equine red blood cell KCl fluxes. The importance of these observations to equine red blood cell homeostasis and haemodynamics is discussed. PMID- 7873168 TI - An efficient method for microinjection of mRNA into Drosophila embryos. PMID- 7873169 TI - Sensitive, nonradioactive northern blots using alkaline transfer of total RNA and PCR-amplified biotinylated probes. PMID- 7873170 TI - An improved method of genomic DNA extraction for screening transgenic mice. PMID- 7873171 TI - A PCR enzyme immunoassay for detection of Salmonella typhi. PMID- 7873172 TI - Reduction of enzyme adsorption to polypropylene surfaces in the presence of a nonionic detergent. PMID- 7873174 TI - An optimized electroporation protocol applicable to a wide range of cell lines. AB - A number of transfection methods for mammalian cells are available; however, many cell lines may appear resistant to efficient transfection, or at best, necessitate lengthy optimization procedures in recommended protocols. We describe here an electroporation protocol that yields highly efficient gene transfer (20% 100% of surviving cells) in all 19 cell lines tested so far, including lymphoid, myeloid, glial, fibroblast and COS cells. Unlike earlier electroporation protocols, adaptation of this protocol to a cell line of interest only requires the optimization of a single parameter, i.e., the voltage, and can be performed within a day. Furthermore, it is also superior to transfection protocols for other methods (calcium phosphate precipitation, lipofection, DEAE-dextran transfection and transferrinfection) in terms of reproducibility, economy and average transfection efficiency for a wide variety of cell lines. PMID- 7873173 TI - Cloning of 5' cDNA regions by inverse PCR. PMID- 7873175 TI - Rapid analysis of the short tandem repeat HUMTH01 by capillary electrophoresis. AB - Using capillary electrophoresis, we demonstrate separation and analysis of the short tandem repeat HUMTH01 in under 10 min with 3 bp resolution. Separation of the PCR products, which range in size from 179 to 203 bp, is achieved using hydroxyethyl cellulose as the separation medium and a novel single-step voltage gradient. Internal standards on either side of the alleles are used to size the PCR products with an average standard deviation of 0.5 bp. DNA typing patterns obtained with this system are compared to samples separated by polyacrylamide slab gel electrophoresis. PMID- 7873176 TI - Detection of loss of heterozygosity by a tube-based assay. AB - Here we report a tube format for detecting loss of heterozygosity in human genomic DNA. This method is based on the detection of a polymorphic restriction site in the selected gene by tube support analysis. After a PCR, amplification products were hybridized to an 125I-labeled oligonucleotide probe and affinity collected on a tube. The captured hybrids were then subjected to an enzymatic digestion, and the remaining bound radioactivity was measured. The usefulness of this technique is illustrated by analyzing the p53 gene LOH in human colorectal samples. This development, similar to immunoanalysis tests, eliminates the electrophoresis step and makes the results easy to study. PMID- 7873177 TI - Increasing proportions of uracil in DNA substrates increases inhibition of restriction enzyme digests. AB - Techniques that rely upon the incorporation of uracil into DNA are being published with increasing frequency, especially in PCR protocols. We report here the efficiency of 18 type II restriction enzymes to digest PCR amplicons synthesized with varying proportions of TTP to dUTP in the PCR mixture. We find that most enzymes with A:T/U bp in their recognition site digest the amplicons less efficiently as the percentage of dUTP in the reaction mixture is increased. This effect is most dramatic when the proportion of dUTP in the nucleotide mixture exceeds 50%. All but one of the enzymes which fail to digest amplicons that are synthesized with 100% dUTP digest some amplicons which are synthesized with 90% dUTP. PMID- 7873178 TI - Enzymatic elongation of microsatellite oligomers for use in direct-label chemiluminescent hybridizations. AB - Short, synthetic oligonucleotide sequences representing microsatellites and other short tandem repeats can be elongated (concatamerized) using a simple method in which complementary strands are annealed, phosphorylated, primer extended and ligated. When used in direct-label chemiluminescent hybridizations, the elongated microsatellite sequences provide an approximately 30-fold increase in signal strength compared with microsatellite oligomers that have not been concatamerized. Concatamerization of simple repeat oligomers further enables the use of relatively short oligonucleotide sequences in direct-label chemiluminescent hybridization experiments, thereby reducing the overall need for radioisotopes in certain commonly performed laboratory procedures such as DNA fingerprinting and selection of clones containing microsatellite sequences. PMID- 7873179 TI - Extraction of DNA from mucilaginous tissues of a sea slug (Elysia chlorotica). AB - Efforts to study the cellular and molecular biology of the symbiotic association between opisthobranch molluscs and algal chloroplasts have been hampered by the copious amounts of mucus produced by the animals. We report for the first time a procedure for isolating total DNA free of contaminating mucilaginous compounds from the mollusc Elysia chlorotica Gould that harbors photosynthetically active chloroplasts from the siphonaceous alga, Vaucheria litorea C. Agardh. This method involves an initial extraction of fresh or freeze-dried Elysia tissue in absolute ethanol and differential processing of the resultant two-phase pellet. Final purification by CsCl-gradient centrifugation produces high molecular weight DNA suitable for molecular analysis. PMID- 7873180 TI - Rapid regeneration of virus from cells infected with a retroviral vector. AB - Recombinant retroviral vectors usually encode the genes of interest in place of the viral structural genes, which must be provided in trans. These viruses are therefore defective for replication: infected cells cannot produce progeny virus. However, in some cases it may be desirable to generate virus from an infected cell clone displaying a phenotype of interest. We describe a rapid method for producing virus, which involves fusing the infected cells to fresh packaging cells. Stable producer lines are generated after fusion by co-selecting for the Ecogpt+ marker in the packaging cells and the G418 resistance (neor) marker in the infected cells. We have used this method to develop cell lines that produce retroviruses encoding a Leu 61-activated c-Ha-ras oncogene as well as a neor gene. The viruses confer oncogenic transformation on 95%-100% of infected target cells as assayed by altered morphology, focus formation and soft agar growth. PMID- 7873181 TI - Long-term episomal gene delivery in human lymphoid cells using human and avian adenoviral-assisted transfection. AB - Human B-lymphoblastoid cells transformed by Epstein-Barr virus (EBV), a common source of established human cell lines, are generally refractory to standard DNA transfection methods. We report here the use of human and chicken adenoviruses for the stable delivery of plasmid DNA carrying the latent origin of replication, oriP, from EBV into human B-lymphoblastoid cells. Long-term hygromycin-resistant transformants of human lymphoblastoid cells belonging to the genetically unstable inherited disease Fanconi's anemia were obtained by adenoviral-assisted transfection of plasmid DNA complexed to either human adenovirus type 5 (Ad5) or avian adenovirus type 1 (CELO). Successful long-term transformation of human lymphoblastoid cells was unrelated to the efficiency of short-term transfection as measured by the transient expression level of a reporter lacZ gene. The human or avian adenoviral binary conjugates, with no other cell ligand, were sufficient for stable cell transformation. The amount of DNA established in the human B-cell transformants was approximately 100-fold higher with the CELO virus. We conclude that Ad5-assisted transfection is more suitable for transient gene expression studies in human lymphoblastoid cells, while CELO-assisted transfection appears the method of choice for stable genetic transformation of such cells. Such differential short- and long-term gene delivery strategy with Ad5 and CELO may be useful in gene therapy of human B cells involving cancers and inherited diseases, respectively. PMID- 7873182 TI - Combinatorial libraries of proteins: analysis of efficiency of mutagenesis techniques. AB - A number of considerations are made on the efficiency of mutagenesis techniques used in protein engineering, particularly those that include a random component. The expected outcome of different protocols is analyzed using computer programs. Special emphasis is made on the effect that the degeneracy of the genetic code has on the bias of the representation of amino acid replacements. The consequences of using alternative methods is analyzed in terms of the likelihood of obtaining underrepresented amino acid substitutions in mutant libraries. A consideration is also made of the outcome of combinatorial mutagenesis experiments with regard to the size of the amino acid window and the multiplicity of replacements that could be sampled with different methods. Optimal mutagenesis rates for specific conditions could be derived from the presented data and the computer program made available with this paper. PMID- 7873183 TI - SIZE: a program to determine the size of nucleic acid and protein molecules from gel mobilities. AB - The relationship between fragment length and the reciprocal of mobility and the least-squares curve fitting analysis for this relationship have been combined into a user-friendly program for determining the size of unknown DNA fragments by reference to known standards. Protein sizes can be determined in the same way. The program offers an accurate, simple-to-use mechanism for sizing molecules that requires only an IBM-compatible computer. PMID- 7873184 TI - A DNA sequence editor with voice input and output. AB - DNA sequence editors for IBM PC-compatible computers are often line-oriented, with complicated methods of entering and modifying sequences. This paper describes SE, a full-screen sequence editor that is operated like a word processor. Features include keyboard entry of new sequences, ability to search for patterns or sequence features, ability to switch strands, and ability to renumber and rotate circular sequences. The entry of new sequences can be confirmed by a spoken voice, and for proofreading, SE will read a sequence aloud using the PC's speaker. If the computer is fitted with a sound board and speech recognition software, SE will also allow voice-input of sequences. Sequences are saved on a file in a format that is compatible with most sequence-analysis programs. PMID- 7873185 TI - A simple microassay for computing the hemolytic potency of drugs. AB - A simple microassay and computer program are described for determining the erythrocyte hemolytic potency of drugs in vitro. This microassay is sensitive for both micro as well as macro ranges of hemoglobin concentration. An ELISA reader has been adapted to read erythrocyte lysis (hemolysis), which reduces the number and culture of replicates. A computer program was developed that calculates parameters such as C50 (concentration of drug causing 50% hemolysis), C100 (concentration of drug causing 100% hemolysis) and beta (slope of the curve) and graphically expresses the hemolytic patterns of various drugs simultaneously. The program can obtain optical densities directly from a 96-well plate ELISA reader by interfacing the microplate reader to the computer or by using a keyboard. This method is useful for screening a large number of hemolytic drugs and requires lower amounts of test compounds. It may also be applicable to quantitative functional assays, such as complement-mediated hemolysis and enumeration of antibody-secreting cells. The program can be obtained from the authors on request. PMID- 7873186 TI - A program for analyzing enzyme rate data obtained from a microplate reader. AB - A computer program (microplate analysis [MPA] program) is described that allows manipulation of kinetic data obtained from a microplate reader. It is particularly useful for obtaining enzyme velocities from microplate data. Data can be displayed either as an 8 x 12 grid which shows all microplate wells at low resolution or as single enzyme progress curves which show the reaction time course in greater detail and allow data manipulation (single curve mode). In the single curve mode, the X-axis of the progress curves can be displayed either as discrete time points numbered from the first to the last or as real time in seconds. The program can calculate the maximum, minimum or initial reaction rate by either linear or robust regression. In the single curve mode, the user can control the range of data points included in the regression analysis and the number of data points over which the rate is averaged. In this way, the maximum (or minimum) rate within a specific range of data can be determined. The major advantage of the MPA program is that the range settings are specific to each well. This gives the user complete control over the presentation and calculation of the kinetic data. The MPA program requires an AS-CII file containing data blocks of 96 sequential absorbance readings for each time point and the time interval between successive absorbance readings. PMID- 7873187 TI - Optical manipulations of human gametes. AB - Optical manipulations of human gametes are described indicating their potential for use in in vitro fertilization and preimplantation-assisted zona pellucida hatching. Successful manipulations are demonstrated using focused laser beams in association with microscopy. The micromanipulation and selection of male gametes were achieved using an optical-trapping infrared laser diode. The opening of the zona pellucida surrounding the egg (assisted hatching) was performed using a pulsed, nitrogen-pumped dye laser. Clinical applications for laser-assisted reproduction techniques are discussed. PMID- 7873188 TI - A third generation immunoassay for tumor necrosis factor alpha. AB - Tumor necrosis factor alpha (TNF alpha) is a polypeptide cytokine produced primarily by monocytes and macrophages. It is involved in a wide variety of immune reactions. Measurement of TNF alpha originally depended upon bioassays that are of varying reliability and reproducibility. Early immunoassays for TNF alpha required handling of radioisotopes and costly disposal of radioactive waste. Subsequent use of enzymes as reporter molecules in enzyme immunoassay (EIA) has eliminated the burden of radioisotope handling and its associated costs. However, EIA has presented new challenges. Use of thimerosal as a preservative in EIAs may require high disposal costs due to its mercury content. In addition, many EIAs lack the sensitivity achievable in radioimmunoassay (RIA). We have developed a simple microplate enzyme-linked immunosorbent assay (ELISA) for the detection of TNF alpha in serum, plasma and culture supernatants. Our high affinity capture antibody has enabled us to achieve a sensitivity of 1.5 pg/mL. The assay is calibrated to the World Health Organization (W.H.O.) first international standard for TNF alpha (87/650) and exhibits excellent precision and reproducibility. Tetramethylbenzidine is used to generate the colored end product of the reaction, and thimerosal has been removed from all components. PMID- 7873189 TI - Leukocyte transmigration, chemotaxis, and oxygenated derivatives of arachidonic acid: when is chirality important? PMID- 7873190 TI - Allergen-induced airway inflammation and bronchial responsiveness in wild-type and interleukin-4-deficient mice. AB - T helper 2 (Th2)-like cytokines are thought to play a crucial role in the pathogenesis of airway inflammation in atopic asthma, leading to bronchial hyperresponsiveness. To investigate the role of the principal Th2 cytokine interleukin-4 (IL-4) in asthma, we examined the allergen-induced changes in airway morphology and bronchial responsiveness (BR) in an in vivo mouse model. C57BL/6 mice were actively sensitized to ovalbumin (OVA) and exposed daily to aerosolized OVA or saline (SAL) for 7 days. Twenty-four hours after the last allergen exposure, total and differential counts of bronchoalveolar lavage cells revealed a significant increase of eosinophils and lymphocytes in OVA-exposed immunized mice compared with SAL-exposed animals. In IL-4-deficient (IL-4-/-) mice, treated in the same way, there were substantially fewer eosinophils in bronchoalveolar lavage compared with wild-type mice. Allergen exposure of actively sensitized wild-type mice induced a significant increase of BR to carbachol and to serotonin compared with SAL-exposed mice. In contrast, OVA exposure of immunized IL-4-/- mice did not augment BR to serotonin compared with SAL-challenged IL-4-/- mice. In conclusion, these data indicate that repeated allergen exposure in sensitized mice induces airway inflammation and bronchial hyperresponsiveness, and that IL-4 plays a predominant role in the pathogenesis of both phenomena. PMID- 7873191 TI - 5-Hydroxyeicosatetraenoic acid (HETE)-induced neutrophil transcellular migration is dependent upon enantiomeric structure. AB - The 5(R) and 5(S) hydroxyeicosatetraenoic acids (5[R]-HETE, 5[S]-HETE) are important inflammatory mediators in lung diseases: they increase mucus, induce airway contraction, and potentiate neutrophil chemotaxis. Neutrophils are important cells in allergic and inflammatory lung diseases. Therefore, we examined the effects of both 5(R)-HETE and 5(S)-HETE on human neutrophil migration across naked filters and human umbilical vein endothelial (HUVE) cell and human type II-like pulmonary epithelial cell (A549) monolayers cultured on these filters. Time courses for both 5(R)-HETE and 5(S)-HETE show significant neutrophil migration at 40 min and maximal migration at 60 to 90 min through all three barriers. Checkerboard analysis showed that migration was chemotactic. Dose response curves for both isomers through cellular monolayers had the same shapes, but 5(R)-HETE was more potent than 5(S)-HETE. There was greater migration through cellular barriers than through naked filters. Actinomycin D pretreatment of the cellular monolayers slightly inhibited the neutrophil transcellular chemotactic response to both 5-HETEs equally. Enhanced transcellular migration was not due to the production of a soluble chemotactic factor. Thus, although both isomers of 5 HETE were potent chemotactic agents, 5(R)-HETE was slightly more potent. Moreover, relevant endothelial and epithelial monolayers enhance both dose- and time-dependent neutrophil migration stimulated by 5(R)-HETE and 5(S)-HETE. These data indicate that (1) both 5(R)-HETE and 5(S)-HETE are important in mediating lung inflammatory processes, and (2) 5(R)-HETE may play a more important role in neutrophil-rich lung inflammatory responses than 5(S)-HETE because it is a more potent inducer of neutrophil migration through endothelial and epithelial barriers. PMID- 7873193 TI - Hyperoxia amplifies TNF-alpha production in LPS-stimulated human alveolar macrophages. AB - Human alveolar macrophages (AM) produce a number of inflammatory mediators including tumor necrosis factor (TNF). TNF-alpha has been implicated in several forms of lung injury including that associated with oxygen toxicity. To investigate whether oxygen could induce or augment the release of TNF from AM, we acquired AM from nonsmoking volunteers and determined TNF release after in vitro hyperoxia. Although TNF release was not induced by oxygen exposure alone, if lipopolysaccharide (LPS) stimulation occurred simultaneously, there was significant augmentation by 60 and 95% oxygen over LPS-stimulated AM exposed to 21% oxygen. This increase was paralleled by a significant increase of interleukin (IL)-1 beta. Dimethylthiourea (DMTU), a hydroxyl radical scavenger, inhibited this release. The increase in TNF extracellular concentrations induced by hyperoxia was not associated with significant increases in intracellular concentration or detectable mRNA over LPS-stimulated AM exposed to 21% oxygen. We hypothesize that hyperoxia exposure may alter the LPS-stimulated AM cytoplasmic milieu, thus further enhancing TNF-alpha production by a post-transcriptional mechanism. PMID- 7873192 TI - Bronchoalveolar lavage fluid from immature rats with hyperoxia-induced airway remodeling is mitogenic for airway smooth muscle. AB - We previously demonstrated that hyperoxia-exposed immature rats develop airway smooth muscle layer thickening; this remodeling appears partially attributable to smooth muscle hyperplasia. In this study, we tested the hypothesis that excess mitogenic activity for airway smooth muscle cells is present within the lungs of hyperoxia-exposed immature rats. We assessed the proliferative effect of bronchoalveolar lavage (BAL) fluid from air- and O2-exposed animals on cultured rat tracheal smooth muscle cells. BAL fluids from air- or O2-exposed immature rats increased DNA synthesis ([3H]-thymidine incorporation at 24 h of incubation) and cell number (compared with DMEM-treated control cells, at 2 days of incubation), but BAL fluid from O2-exposed animals had significantly greater mitogenic effects. This excess mitogenic activity was lipid inextractable and was ablated by trypsin digestion, indicating that at least one polypeptide growth factor was responsible; molecular sieve fractionation demonstrated a molecular weight of > 10 kD. Because platelet-derived growth factor (PDGF) has been identified in other models of hyperoxia exposure, we tested the further hypothesis that PDGF contributes to the observed excess mitogenic activity. Addition of neutralizing anti-PDGF antibodies to BAL-stimulated smooth muscle cultures did not reduce BAL fluid-induced mitogenesis. These data indicate that the lungs of O2-exposed rats contain excess mitogenic activity for airway smooth muscle, attributable to non-PDGF polypeptide growth factors. It is conceivable that this abnormal mitogenic activity contributes to O2-induced airway smooth muscle remodeling observed in immature rats in vivo. PMID- 7873194 TI - Differential expression of annexins I and II in bovine bronchial epithelial cells. AB - Annexins I and II have been proposed to participate in regulation of inflammation and cell proliferation. In the present study, we examined the expression of annexins I and II in various levels of the bovine respiratory tract and in cultured bovine bronchial epithelial cells. Immunoblot analysis of whole-tissue extracts revealed low-level expression of annexins I and II in bronchial mucosa mainstem to fourth generation. In contrast, high levels of annexins I and II (15- to 20-fold higher than in the bronchial mucosa) were seen in the distal lung parenchyma. Immunohistochemical staining of tracheobronchial tissue sections with anti-annexin I antibody revealed an uneven positive reaction of about 30 to 40% of the columnar differentiated ciliated and secretory cells, with no obvious positivity within the nondifferentiated basal epithelial cell layer. In contrast, anti-annexin II antibody reacted nearly uniformly within the basal cell layer, with no obvious decoration of the differentiated cell types. These results were confirmed by immunoblot analysis of annexin I and II in density fractionated populations of basal and secretory/ciliated epithelial cells. Both annexins I and II were expressed at constitutive levels in bovine bronchial epithelial cells grown in glucocorticoid- and serum-free medium, and dexamethasone increased expression of both proteins in a concentration-dependent manner. We conclude that annexins I and II are differentially expressed in the differentiated ciliated cells and undifferentiated basal cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873195 TI - Retinoic acid inhibition of transforming growth factor-beta-induced collagen production by human lung fibroblasts. AB - Transforming growth factor-beta (TGF-beta)-stimulated collagen production plays an important role in the pathogenesis of the fibrotic response seen in chronic inflammatory lung disorders. Retinoids are vitamin A analogues that are potent immunomodulators and have been shown to modulate stromal cell collagen production in a variety of nonpulmonary systems. We hypothesized that retinoids might also modulate lung fibroblast collagen production. To test this hypothesis, we determined whether all-trans retinoic acid (RA) and several other retinoid compounds regulate the production of types I and III collagen by unstimulated and TGF-beta 1-stimulated human lung fibroblasts. Unstimulated cells produced modest quantities of types I and III collagen, and TGF-beta 1 increased the production of these matrix molecules 2- to 4-fold. Preincubation with 10(-5) M RA caused a significant decrease in the basal levels of types I and III collagen produced by these cells. RA preincubation also totally abrogated the collagen inductive effects of TGF-beta 1. At 10(-5) M, RA preincubation caused a 97% decrease in the stimulation of type I collagen and a 115% decrease in the stimulation of type III collagen caused by TGF-beta 1. These inhibitory effects were dose dependent. Significant inhibition of type I and III collagen production was appreciated with doses of RA as low as 10(-9) and 10(-8), respectively. These inhibitory effects were not unique to RA since 13-cis-retinoic acid, 9-cis-retinoic acid, etretinate, all-trans etretin, and the water-soluble retinoids, retinoyl beta glucuronide and retinyl-beta-glucuronide, also inhibited TGF-beta 1-stimulated type I collagen production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873197 TI - Concurrent increases in the storage and release of mucin-like molecules by rat airway epithelial cells in response to bacterial endotoxin. AB - Mucus hypersecretion is a prominent response of the airways to bacterial infections. Recent findings showed that bacterial endotoxin, a lipopolysaccharide complex released from the bacterial cell wall, was able to induce at least one component of the hypersecretory response, i.e., an increase in the amount of stored epithelial mucosubstances (1, 2). The goal of the present study was to determine whether endotoxin also was capable of increasing mucosubstance release from cells. Based on evidence that human mucin antibodies A10G5 and B6E8 cross reacted with rat mucin-like molecules, we used the antibodies in enzyme-linked immunosorbent assays (ELISA) to compare mucin concentrations in bronchoalveolar lavage (BAL) fluid from endotoxin-treated and control rats. Results showed that endotoxin treatment increased the amount of released mucin over that in controls 1.5-fold at 96 h and 2.5-fold at 168 h after instillation. Thus, these studies have defined the previously detected mucosubstances as mucin-like molecules and showed that endotoxin increases their release from, as well as their storage in, rat airway epithelium. Concurrent increases in storage and release suggest that endotoxin also stimulates mucin synthesis and/or stability. PMID- 7873196 TI - Mucus glycoconjugate complexes released from feline trachea by a bacterial toxin. AB - This paper describes low-density mucus glycoconjugates released from feline trachea by dirhamnolipid (DRL), a toxin from Pseudomonas aeruginosa. Mucus glycoconjugates in feline tracheas were radiolabeled in vivo with 3H-proline and 14C-glucose. Control mucus and that released by 200 micrograms/ml DRL were dissolved in guanidine hydrochloride buffer (GuHCl) and chromatographed on Sepharose CL-2B. Molecules eluting in the void volume (V0) of the column were isolated by isopycnic density gradient centrifugation in CsCl/GuHCl. All samples gave peaks of radiolabeled and periodic acid/Schiff (PAS)-reactive material at rho = approximately 1.50 and approximately 1.60 g/ml, but DRL-stimulated samples contained low-density material (rho < 1.32 g/ml), also PAS-reactive and radiolabeled. Control secretions incubated with DRL in vitro did not form low density material. In Triton X-100 (1% vol/vol), a nonionic detergent, low-density material behaved as smaller molecules, running in the partially included volume (Vi) of the column of Sepharose CL-2B, but still in the V0 of Sephacryl S-300. Incubation with chondroitinase ABC, heparinase II and III, and keratanase failed to change its elution profile on S-300, evidence against glycosaminoglycans; but proteolysis with trypsin or proteinase K gave two peaks, peptide fragments near the totally included volume of the column and glycopeptides in V0. The V0 glycopeptides banded between 1.50 and 1.55 g/ml in a CsCl gradient and eluted as a single peak in the Vi of Sephacryl S-400, suggesting a distinct homogeneous glycopeptide, smaller than those from normal mucins. The main 14C-labeled sugars in this glycopeptide were fucose, glucosamine, galactosamine, and galactose, consistent with a mucin. Thus, DRL releases stable but noncovalent complexes containing one or more distinct mucinlike glycoconjugates, probably combined with lipids and peptides. We discuss their possible relevance to airway diseases, including cystic fibrosis. PMID- 7873198 TI - Pretreatment with an antibody to interleukin-5 prevents loss of pulmonary M2 muscarinic receptor function in antigen-challenged guinea pigs. AB - Inhalational challenge with antigen decreases the function of inhibitory M2 muscarinic autoreceptors on parasympathetic nerves in the lung, increasing the release of acetylcholine from the vagus nerves and potentiating vagally induced bronchoconstriction. It is possible that eosinophils cause M2 receptor dysfunction, perhaps by releasing positively charged proteins that are M2 receptor antagonists. Because of the probable role of interleukin-5 in initiating and maintaining the eosinophil infiltration, we tested the function of neuronal M2 receptors in antigen-challenged guinea pigs after pretreatment with a monoclonal antibody to interleukin-5 (TRFK-5). Ovalbumin was given intraperitoneally to sensitize the animals. Three weeks later, the animals were injected intraperitoneally with either TRFK-5 (240 micrograms/kg i.p.) or saline. Beginning three days later, they were challenged with an ovalbumin aerosol for 5 min on each of four consecutive days. M2 receptor function was tested 24 h after the last antigen challenge. Electrical stimulation of both vagi caused bronchoconstriction and bradycardia. In control animals, pilocarpine attenuated, and gallamine potentiated, vagally induced bronchoconstriction by stimulating and blocking neuronal M2 muscarinic receptors, respectively. In challenged animals that did not receive TRFK-5, these effects were markedly reduced, confirming M2 receptor dysfunction. In TRFK-5-treated guinea pigs, the effects of both pilocarpine and gallamine were the same as those in control animals, demonstrating normal M2 receptor function. Pretreatment with TRFK-5 selectively inhibited the migration of eosinophils into the lungs as measured by lung lavage. Thus the function of M2 muscarinic receptors in antigen-challenged guinea pigs can be protected by inhibiting eosinophil influx into the lungs. PMID- 7873199 TI - Regulation of ciliated cell differentiation in cultures of rat tracheal epithelial cells. AB - The cellular pathway of ciliated cell differentiation and its regulation is poorly defined. To begin to understand the process of ciliated cell differentiation, we sought to identify factors regulating ciliated cell development in vitro. Rat tracheal epithelial (RTE) cells were cultured on collagen gel-coated membranes at an air-liquid interface in hormone- and growth factor-supplemented medium (complete medium [CM]). Under these conditions, RTE cells first proliferate and then differentiate into a pseudostratified mucociliary epithelium. Ciliated cell differentiation was measured using a monoclonal antibody, RTE3, which was shown to specifically react with the plasma membrane of ciliated cells. Cultures were immunostained in situ, and the percentage of the culture surface covered with ciliated cells was estimated using videomicroscopy and an image analysis program. If an air-liquid interface was not created and the cells were maintained in the submerged state, ciliated cell differentiation was suppressed 25-fold. Culture in the absence of mitogenic components present in CM, including epidermal growth factor (EGF), cholera toxin (CT), or bovine pituitary extract, resulted in 2- to 4-fold increases in the percentage of ciliated cells. When both EGF and CT were removed from the media, DNA synthesis and total cell number was reduced, while ciliated cell differentiation increased as much as 5-fold. These results demonstrate that submersion inhibits, while withdrawal of mitogenic compounds promotes, ciliated cell differentiation in vitro. PMID- 7873200 TI - Role of endogenous cytokines in endotoxin- and interleukin-1-induced pulmonary inflammatory response and oxygen tolerance. AB - Endotoxin lipopolysaccharide and the cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), are known to protect adult rats against O2 toxicity. However, whether the effect of endotoxin is mediated by these cytokines is not clear. We have previously demonstrated that depletion of 84% rat alveolar macrophages (AM), which reduced lipopolysaccharide (LPS)-induced release of TNF by 86%, had no effect on LPS-induced O2 tolerance. In this study, we demonstrated that coinsufflation of LPS with anti-TNF antibody and IL-1 receptor antagonist (IL-1ra), which completely inhibited LPS-induced TNF and IL-1 activities, had no effect on LPS-induced alveolar inflammatory response and O2 tolerance. Likewise, coinsufflation of IL-1 and anti-TNF antibody, which completely neutralized IL-1 induced TNF activity, had no effect on IL-1-induced alveolar inflammatory response and O2 tolerance. In contrast, IL-1ra completely abolished IL-1-induced inflammatory response and markedly inhibited IL-1-induced O2 tolerance. These results suggest that LPS-induced alveolar inflammatory response and O2 tolerance are not mediated by endogenous TNF and IL-1. Similarly, endogenous TNF does not mediate IL-1-induced alveolar inflammatory response and O2 tolerance. PMID- 7873201 TI - Airway neutrophilia and chemokine mRNA expression in sulfur dioxide-induced bronchitis. AB - Airway inflammation in acute and chronic bronchitis includes a prominent neutrophil influx. Using a rat model of sulfur dioxide (SO2)-induced bronchitis, we investigated the role of the polymorphonuclear leukocyte (PMN) chemokines macrophage inflammatory protein-2 (MIP-2) and KC. Adult female rats were exposed to 230 ppm SO2 for 5 h/day for periods of 1 day to 5 wk. Immunohistochemical identification of rat PMNs in trachea cryostat sections allowed quantitation of a marked neutrophil influx into airways of bronchitic rats (PMNs/trachea ring = 55 +/- 26.2 [1 day SO2] versus 3.6 +/- 2.7 [air]; n = 5, P < or = 0.05). Northern analysis of trachea homogenates demonstrated induction of KC and MIP-2 mRNA expression after 1 day of SO2 and persistence of increased expression after longer exposure periods examined. Pretreatment of rats with dexamethasone (0.5 mg/kg) prior to a 1-day acute SO2 exposure prevented induction of chemokine mRNA and abrogated neutrophil influx completely (PMNs/trachea ring = 6.6 +/- 8.8 versus air controls; n = 5, P = 0.96). To determine if chemokine inhibition by dexamethasone could be further studied in vitro, the rat alveolar macrophage cell line NR8383 was treated with dexamethasone (10(-7) M) before stimulation with lipopolysaccharide (10 micrograms/ml). Pretreatment with dexamethasone substantially decreased induction of both MIP-2 and KC mRNA in response to lipopolysaccharide, indicating the potential utility of in vitro systems to identify additional anti-inflammatory agents. These studies support the hypothesis that the chemokines MIP-2 and KC mediate airway neutrophil influx in both acute and chronic SO2-induced bronchitis in the rat. PMID- 7873203 TI - Induction of cyclooxygenase-2 is responsible for interleukin-1 beta-dependent prostaglandin E2 synthesis by human lung fibroblasts. AB - Because interleukin-1 beta (IL-1 beta) increases the synthesis of prostaglandin E2 (PGE2) in human lung fibroblasts, the effect of IL-1 beta on the expression of two isozymes of cyclooxygenase (cyclooxygenase-1 and -2) in human embryonic lung fibroblasts (IMR-90) was investigated in terms of three parameters (PGE2 release, cyclooxygenase activity, and mRNA). When the cells were incubated with IL-1 beta, both the PGE2 release to the culture medium and the cyclooxygenase activity in the cell lysate increased in a dose- and time-dependent manner, and both were inhibited by NS-398 (a cyclooxygenase-2-specific inhibitor). Dexamethasone and interleukin-4 (IL-4) inhibited the IL-1 beta-induced PGE2 synthesis; the former inhibited the IL-1 beta-induced cyclooxygenase activity whereas the latter failed. As analyzed by Northern blot, cyclooxygenase-1 mRNAs (3.0 Kb and 5.0 Kb) were detected with resting cells and did not increase by the addition of IL-1 beta. In contrast, the cyclooxygenase-2 mRNA (4.4 Kb) was undetectable with resting cells, but was increased dramatically up to 4 to 8 h by the addition of IL-1 beta. Dexamethasone inhibited the IL-1 beta-induced mRNA expression of cyclooxygenase-2 whereas IL-4 failed. These results indicate that IL-1 beta induces cyclooxygenase-2 rather than cyclooxygenase-1 in IMR-90 cells and this induction is responsible for the augmentation of PGE2 production stimulated with IL-1 beta. However, the inhibition of the IL-1 beta-induced PGE2 synthesis by IL 4 was not mediated by the down-regulation of cyclooxygenase-2. PMID- 7873202 TI - Human neutrophil defensin and serpins form complexes and inactivate each other. AB - Defensins, antimicrobial and cytotoxic peptides of neutrophils, bind to and are inactivated by blood proteins. We identified defensin interactions with alpha 1 proteinase inhibitor (alpha 1-PI), alpha 1-antichymotrypsin (alpha 1-ACT), alpha 2-antiplasmin (alpha 2-AP), and antithrombin III (AT III) and examined defensin binding to alpha 1-PI and alpha 1-ACT in more detail. Defensin interactions with either alpha 1-PI or alpha 1-ACT were not affected by iodoacetamide or high salt concentration. Preincubation of alpha 1-ACT or alpha 1-PI with increasing concentrations of defensin resulted in a progressive decrease of antiprotease activity of both inhibitors against cathepsin G and antiprotease activity of alpha 1-PI against human neutrophil elastase. At higher concentrations, defensin also ablated the inhibitory effect of normal human serum on cathepsin G and human neutrophil elastase. Both alpha 1-PI and alpha 1-ACT inhibited defensin cytotoxicity toward the human lung carcinoma cell line A549, whereas the elastase inhibitor antileukoprotease did not. Complex interactions between serpins and defensin may have a role in regulating inflammatory processes. PMID- 7873204 TI - Benign gynecologic disease: applications of magnetic resonance imaging. AB - Magnetic resonance imaging (MRI) can contribute to cost-effective management in women with suspected myomas or adenomyosis and can provide precise presurgical mapping prior to myomectomy or correction of mullerian duct anomalies. MRI is also valuable in patients with suspected adnexal masses that are not detected sonographically or where definitive diagnosis of juxtauterine myoma, cystic teratoma, or hemorrhagic mass may alter management. PMID- 7873205 TI - Magnetic resonance imaging of the female pelvis: technical considerations. AB - To perform magnetic resonance imaging of the female pelvis, one must be familiar with the imaging appearance of normal structures as well as the disease entities that may be encountered. However, it is also important to be familiar with and understand the basic physical principles of the available imaging techniques to be able to optimize image quality and the detection of abnormalities. This discussion is intended to describe the available imaging techniques used in evaluation of the female pelvis. Following a discussion of conventional spin echo (CSE) techniques, the fast spin echo (FSE) technique will be described in detail. This will include how the FSE sequence generates images, the choice of imaging parameters, and the unique contrast characteristics and artifacts associated with the FSE technique. Pelvic multicoils will also be described in detail, including the choice of imaging parameters when using these coils and the unique artifacts that can be encountered. Chemical-selective imaging and motion artifact reduction techniques will additionally be described. At the end of the discussion, suggested imaging parameters are given for CSE and FSE sequences and for body coil and multicoil imaging. PMID- 7873206 TI - Malignant gynecologic disease: applications of magnetic resonance imaging. AB - Malignancies of the female genital tract account for 25% of all cancers diagnosed in women. The decreasing incidence and mortality associated with cervical and uterine corpus carcinomas reflect earlier detection and improved therapies. Although not practical as a screening tool, magnetic resonance imaging is playing an expanding role in the diagnosis and staging of gynecologic cancers. Its unsurpassed soft tissue contrast resolution and multiplanar imaging capabilities allow better depiction of depth of tumor invasion and extent of local spread than either computed tomography or ultrasound. PMID- 7873207 TI - Methods and material. PMID- 7873208 TI - Lymphatic and haematopoietic tissues. PMID- 7873209 TI - Digestive organs. PMID- 7873210 TI - Respiratory system. PMID- 7873211 TI - Breast. PMID- 7873212 TI - Lip, oral cavity, and mesopharynx. PMID- 7873213 TI - Female genital organs. PMID- 7873214 TI - Male genital organs. PMID- 7873215 TI - Urinary tract. PMID- 7873216 TI - Skin. PMID- 7873217 TI - Eye, brain and nervous system. PMID- 7873218 TI - Thyroid, endocrine glands, bone, muscle and connective tissue. PMID- 7873219 TI - Hypertension and atherosclerosis. Therapeutic perspectives. PMID- 7873220 TI - Cardiac morbidity in the human immunodeficiency virus infection. AB - PURPOSE: To evaluate the cardiac involvement in Human Immunodeficiency Virus (HIV) infection. DESIGN: Prospective and normal individuals group controlled study. SETTING: The departments of cardiology and infectious diseases of an university hospital. PATIENTS: 137 consecutive HIV infected patients at all stages of the infection and 40 normal noninfected controls. MEASUREMENTS AND MAIN RESULTS: Clinical and echocardiographic evaluation was performed. Cardiac symptoms were observed in 10 (7.3%) patients, manifested as congestive heart failure. The global HIV infected population had increased left ventricular (LV) dimensions and wall thickness and decreased LV fractional shortening and ejection fraction when compared with the control population. Seven (5.1%) patients had dilated cardiomyopathy, 9 (6.5%) had global LV hypokinesis with or without LV dilatation and 17 (12.4%) had segmental LV wall motion abnormalities. Right ventricular dilatation was present in 23 (16.8%). Mitral or tricuspid regurgitation of a moderate or severe degree was found in 3 (2.2%) patients. No valvular vegetations were found. Fifty nine (43.1%) patients presented a pericardial effusion. An echocardiogram with at least one abnormality was observed in 104 (75.9%) and a severely abnormal echocardiogram in 34 (24.8%). The presence of cardiac symptoms and of abnormal and severely abnormal echocardiograms was more frequent in patients with the acquired immunodeficiency syndrome than in asymptomatic HIV infected patients. When comparing HIV-1 with HIV-2 populations the first showed increased LV systolic and diastolic diameters and LV mass index. There was no statistically significant difference between all risk behavior groups regarding the frequency of cardiac symptoms or the echocardiographic abnormalities found. HIV infected patients with CD4+ lymphocytes counts < or = 100/mm3 had more frequent abnormal and severely abnormal echocardiograms than those with CD4+ lymphocytes counts > 100/mm3. CONCLUSIONS: Although cardiac symptoms were rare in our population, subclinical cardiac involvement detected by echocardiography was frequent and could involve any cardiac layer. It was not influenced by the patients' risk behavior. The left ventricular trophic response observed in HIV-2 infection seemed less intense than that in HIV-1 infection. Cardiac involvement was more frequent in the more advanced stages of the infection and in patients with lower CD4+ lymphocyte counts. PMID- 7873221 TI - [Enalapril reduces the degree of left ventricular remodeling after acute myocardial infarction and reduces the incidence of arrhythmia in ischemic disease]. AB - The present study shows that enalapril prevents the excessive remodeling of the left ventricle after acute myocardial infarction. This randomized and double blind clinical study analysed 50 patients with an inferior myocardial infarction. The effect of enalapril was evaluated through cardiac volumes, ejection fraction, neurohormonal levels and incidence of the left ventricle disfunction after acute myocardial infarction. The patients treated with enalapril showed a significant reduction on the values of nor-epinefrine, angiotensine II, natriuretic hormone and vasopressine, four weeks after initiation of treatment. The ejection fraction and the level of the wall movement was more favourable, four weeks after infarction, in the group treated with enalapril. The incidence of congestive heart failure and arrhythmias was lower in the group treated with enalapril. So, we conclude that enalapril is a drug that prevents the excessive remodelling of the left ventricle after an acute myocardial infarction. PMID- 7873222 TI - [Transesophageal echocardiography assessment of regurgitant jets of eccentric geometry in mitral valve prosthesis: superiority of multiplanar sections over standard sections]. AB - OBJECTIVE: The purpose of this study was to determine whether multiplanar (MP) transesophageal echocardiographic views were superior to standard views (ST) at 0 degree and 90 degrees in the evaluation of mitral prosthesis regurgitation (MR), particularly in presence of wall regurgitant jets. DESIGN: Comparison between MP and ST views in the evaluation of mitral prosthesis regurgitation. SETTING: Laboratory of Echocardiography of the General Hospital Gregorio Maranon. MATERIAL AND METHODS: Study of all mitral prostheses in which pathological mitral regurgitation had been detected by multiplanar TEE, between January 1993 and March 1994. Regurgitation prosthesis were classified in two groups according to the presence of wall regurgitation jets and maximum turbulent color flow areas (MAX) were measured on standard (0 degree and 90 degrees) and MP (0 degree to 180 degrees) views. The sample was divided in two groups, A (n = 33): with wall jets and B (n = 10): without wall jets. Students' t test was used to compare both areas using a 95% confidence interval (95% c.i.). RESULTS: MAX detected on ST views were of 5.80 +/- 4.60 cm2 and on MP were of 7.42 +/- 5.13 cm2 being the difference statistically significant: 1.61 cm2, 95% c.i. from 0.94 to 2.28 cm2, p = 0.000025. MAX for group A was of 5.64 +/- 4.30 cm2 in ST views and of 7.51 +/- 5.12 cm2 in MP views, being the difference 1.86 cm2, 95% c.i. from 1.04 to 2.68; p = 0.00009. Differences for group B were also statistically significant: 0.68 cm2, p = 0.0176. Mitral regurgitation (MR) was classified as mild, moderate and severe according to the color flow area. MP views detected a severer degree of MR than ST views in 8 patients, all of them with wall regurgitation jets. Three of these cases had been considered normal on ST views. CONCLUSIONS: Multiplanar transesophageal views are significantly superior to standard views in the assessment of regurgitant prosthetic mitral valves, particularly in presence of wall regurgitant jets. Our data strongly suggest that multiplanar TEE is the procedure of choice in the assessment of wall regurgitant mitral prostheses. PMID- 7873223 TI - [Holt-Oram syndrome. Review and report of 2 familial cases]. AB - In 1960 Holt and Oram reported a family in which upper extremity malformations were associated with a secundum atrial septal defect. Since then, more than 200 cases have been reported with a wide spectrum of phenotypes. The authors present the cases of one mother and daughter with Holt-Oram Syndrome (SHO). PMID- 7873224 TI - Insights into the role of thromboxane A2 and serotonin in the pathogenesis of unstable angina. AB - New research about platelet and endothelial functions is allowing us to better understand the pathogenesis of myocardial ischemic episodes in patients with unstable angina, creating new perspectives for the rational utilization of therapies. In patients with unstable angina, the episodes of symptomatic and silent ischemia are caused by repeated reductions of coronary blood flow. They are the result of the mechanical effect of the growing thrombus, which causes intermittent episodes of partial obstruction of the arterial lumen, in association with vasoconstriction at the stenotic site and dependent coronary arterial bed, produced by the cyclic release of platelet derived vasoactive products, namely thromboxane A2 and serotonin. Several studies, many of them in animal models of thrombosis, suggest that serotonin and thromboxane A2 are mediators of platelet aggregation, adynamic obstruction and coronary artery thrombosis. Because they cause coronary cyclic flow reductions, they are implicated in the pathogenesis of myocardial ischemic episodes during unstable angina. Drugs that interfere with the arachidonate pathway, and the 5-HT2 receptor antagonists, have been proven to decrease or abolish coronary cyclic flow variations in animal models and man. However, further studies should be done to test the hypothesis that the association of a 5-HT2-receptor antagonist with aspirin may contribute to decrease myocardial ischemia and prevent coronary occlusion in patients with unstable angina. Continuous Holter monitoring during the first week after admission in the hospital should be a good method to evaluate the eventual efficacy of this new class of drugs in abolishing or decreasing the frequency, intensity and duration of myocardial ischemic episodes in patients with unstable angina. The central role of serotonin in the pathogenesis of thrombotic events, and the presumed preventive effect of ketanserin, were the bases of a national multicenter pilot controlled study designed to evaluate the safety and efficacy of ketanserin plus aspirin in the secondary prevention of patients with unstable angina and non-Q wave myocardial infarction (KATUA Trial). PMID- 7873225 TI - [The "obregoes" monks of the congregation of poor male nurses]. PMID- 7873226 TI - [Indices of biomedical bibliography in otolaryngology]. AB - Since 19th century the trends to medical specialization produced an increase of otorhinolaryngological publications. Due to the impossibility for the otorhinolaryngologist to gather all the medical literature, indexes and medical bibliographies have become an essential tool to physicians and medical investigators, helping them to select relevant literature. In the present work we describe the most interesting indexes of biomedical bibliography for the otorhinolaryngologist. Also, we give a list of the seventy most prestigious otorhinolaryngological journals in the world and the repertories in which they are included. PMID- 7873227 TI - [Vestibular compensation. Rehabilitation of a patient with vertigo]. AB - Vestibular compensation is the association of neurological reorganization events that allow to recover the balance after peripheral vestibular damage. The aim of rehabilitation of the patient with vertigo is to maximize these events to achieve an earlier return of the patients to active life. An individualized vestibular rehabilitation program is used on the basis of a general protocol that includes the following four elements: a) stabilization of vision and coordination of head and eye movements; b) vestibular habituation exercises adapted on an individual basis; c) postural control exercises via biofeedback techniques; and d) a program to improve general patient conditions. It is concluded that rehabilitation therapy of vertigo should always be taken into account, both in balance alterations caused by peripheral vestibular lesions and in central nervous damage and mixed pathology. PMID- 7873228 TI - [Experimental study of the utilization of combined interferon chemotherapy in the treatment of laryngeal cancer]. AB - We have studied the effects of different chemotherapy drugs and/or interferons on the laringeal cancer cell line HLa-79. The best anti-proliferative effect was achieved using interferon-beta. A combination of 5-fluoracil and interferon-beta was the only one that resulted in a synergistic anti-proliferative effect. PMID- 7873229 TI - [The maxillary sinus of the rabbit: an experimental model]. AB - The present work describes the anatomy of the rabbit nasal cavity and maxillary sinus. Studies of mucociliary clearance in the maxillary sinus and of the sinus mucosa by light and electronic microscopy are also carried out. PMID- 7873230 TI - [Myringotomy and transtympanic ventilation tubes in secretory otitis media. A study of 108 children]. AB - The aim of this report is to compare the use of tympanostomy tubes (in 190 ears) versus the realization of myringotomy without any posterior placement of tubes (in 19 ears) in the treatment of 108 children with secretory otitis media. Course, sequelae and complications were analyzed over a period of 2 to 9 years. Our results suggest that the use of tympanostomy tubes must follow some specific indications, since they are not free of complications and sequelae. PMID- 7873231 TI - [The treatment of benign paroxysmal positional vertigo]. AB - Medical treatment of the benign paroxysmal positional vertigo has achieved a high relevance in the last fifteen years because this is one of the most frequent types of vertigo. However, at the present time it is not possible to reject the surgical treatment yet. A review of 116 cases with benign paroxysmal positional vertigo has been made. Patients were included in three groups of therapy: pharmacological treatment, postural manoeuvres and a combination of both. Results were categorized in different groups according to the time (1 month, 3 months, 6 months and 1 year) that symptoms took to wear off. The most efficient treatment has been the BRANDT and DAROFF'S manoeuvres in association with vestibular sedatives. PMID- 7873233 TI - [Therapeutic possibilities in recurrent infantile tonsillitis]. AB - The present study compares two therapy protocols in 40 children with recurrent tonsillitis. Twenty of them were randomly treated with penicillin, and the remaining 20 received penicillin + metronidazole. Clinical and microbiological assessment of the results was made. The association of penicillin and metronidazole was most efficient, probably due to its activity against Streptococus pyogenes and anaerobic betalactamase-producing bacterias. The high failure rate in the penicillin group states the necessity to change the therapy with this antibiotic in the treatment of childhood recurrent tonsillitis. PMID- 7873232 TI - [Intraoperative facial nerve monitoring: results]. AB - Intraoperative facial nerve monitoring is performed by electromyographic recording of motor action potentials generated by facial nerve stimulation or mechanical damage of the facial nerve, and helps the surgeon to localize the course of this nerve, reduce the possibility of its injury during surgery, and assure its anatomical and functional integrity. We report our experience on the intraoperative facial nerve monitoring in 35 patients, ten of which belong to absolute indications for monitoring, and to relative indications the remaining cases. In every case, we used the Nerve Integrity Monitor (NIM-2), manufactured by Xomed. Assessment of facial nerve integrity degree is performed pre- and postoperatively using the House-Brackmann classification. We only found in two cases (5.7%) some degree of palsy in the late postoperative period. No correlation was found between the recorded intraoperative response and the functional results in the early postoperative period. PMID- 7873234 TI - [Diagnosis of allergic rhinitis by determining of tryptase and eosinophil cationic protein in nasal secretions]. AB - In the last years, the role of nasal mast cells and the eosinophils in the immediate hypersensitivity reaction of allergic rhinitis has been well documented. Tryptase and the eosinophil cationic protein (ECP) are specific activation markers for mast cells and esosinophils respectively. To determine the possible diagnostic value of these markers in allergic rhinitis we measured the levels in both serum and native nasal fluid using sandwich RIA-assays. Twenty eight seasonal allergic patients (16 with active allergy and 12 with extraseasonal allergy) and 11 patients with chronic sinusitis were studied. Twenty one normal healthy donors served as controls. We could not detect increased levels of tryptase and ECP in the serum of all patients and healthy donors. In contrast, patients with active allergy showed very higher levels of ECP than patients of the three other groups. Similarly, nasal ECP was higher in patients with nasal pathology than in healthy subjects. The highest levels were found in the patients with active allergic rhinitis. Our results show that both native nasal fluid tryptase and ECP can be used as markers of local inflammation and that the assessment of their levels can be useful in the diagnosis and follow up of mucosal inflammation in the nose. PMID- 7873235 TI - [Surgery of paranasal sinuses: evaluation and follow-up of 239 patients operated on by microendoscopy]. AB - Endoscopic surgery has progressed in the 90's, improving many surgical procedures in several specialties, among which, the ENT has been one of the most favored. In the present work we review the clinical features, surgical results and follow up of 239 patients who underwent microsurgery and endoscopic surgery of paranasal sinuses. All the patients were treated with a combined microscopic/endoscopic surgical procedures for recurrent or chronic sinusitis and/or nasosinusal polyposis. We performed 349 surgical procedures in 239 patients: 140 etmoidectomies, 194 procedures in the maxillary sinuses, 12 in the frontal sinuses and 3 in the sphenoidal sinuses. All the patients received previous medical treatment without positive results. Minor complications were present in 2% of the patients and major complications in 1.4% of the patients, that were solved in the immediate postoperatory. Follow up was made in 83% of the cases for a mean period of 20 months (range 12 to 48 months). Good results were obtained in 94% of the patients with chronic or recurrent sinusitis and in 82% of the patients with nasal polyposis. PMID- 7873236 TI - [Postoperative complications in patients with functional neck dissection]. AB - The aim of this study was to assess the complications of surgical treatment of patients with laryngeal cancer undergoing functional neck dissection (FND). Local and medical complications, post-operative sequelae, post-operative stay and fatality rate were recorded in 195 patients. Overall complication rate was 43.07%, with 45 wound infections; 35 wound dehiscences; 39 serohematomas; 4 chylous fistulae; and 11 hemorrhages (2 cases of internal jugular vein rupture). Medical complications were seen in 11 patients. The significant association of pharyngocutaneous fistula with wound infection and dehiscence raises a reasonable doubt about the relative participation of FND in the reported complication rate. Overall incidence of surgical fatality as a result of complications was 2.56% (5/195). Permanent sequelae were found in 4.24% of FNDs (11/259). The average hospitalization was 25.17 +/- 19.88 days. Although an accurate evaluation of intrinsic complications of FND is difficult to perform in patients with combined single-state surgery for the tumor and the neck, most complications of FND are local and easy to manage. PMID- 7873237 TI - [A study of neoadjuvant chemotherapy in the treatment of cancer of pyriform sinuses]. AB - We present a retrospective study of 49 cases of squamous cell carcinoma of the pyriform sinus treated with induction chemotherapy (group I) and compared with 103 cases that did not received this treatment (group II). Thirty four patients were treated with combined cis-platinum and 5-fluoracil. Local and regional control and distant metastasis were analyzed, and no differences between the two groups were found. Five-year global actuarial survival rates were 23% in group I, and 35% in group II (p = no significant). In group I, those cases that responded to chemotherapy had a better 4-year survival rate (33%) than those who did not (7%) (p < 0.1). When patients who underwent radical radiotherapy were analyzed, a better 5-year survival rate was found in group I (41%) versus group II (13%) (p < 0.05). PMID- 7873239 TI - [Thyroplasty in the treatment of functional or paralytic dysphonias]. AB - In phonosurgery, the laryngeal framework surgery, with several types of thyroplasty, allow a modification of the vocal function through an indirect action over the thyroid cartilage, without surgical invasion of the vocal fold tissues. We describe our experience and review the literature in this field. PMID- 7873238 TI - [Clinical application of free microvascular flaps in reconstructive surgery of the oral cavity]. AB - We present the results of reconstructive surgery after different surgical resections in the oral cavity. Reconstruction of the defects was made using free microvascularized flaps. We used a free radial fasciocutaneous or osteocutaneous flap in every case, with a 100% of viability and a low complication rate. This technique is widely versatile in the reconstruction of different oral defects, offering an adequate replacement of oral mucosa. PMID- 7873240 TI - [Hemangiopericytoma of the soft palate and mediastinum: a case report]. AB - We report a case of hemangiopericytoma with simultaneous affectation of soft palate and mediastinum in a 46-year-old male. We describe the outstanding histologic features of this uncommon tumor, as well as its treatment and evolution. This case had a 5-year survival in spite of pulmonary metastases. We also reviewed the literature and discussed this rare clinical presentation of hemangiopericytoma. PMID- 7873241 TI - [Cervical cavernous hemangioma of extramuscular localization]. PMID- 7873242 TI - [Posttraumatic retropharyngeal hematoma of delayed onset]. AB - Retropharyngeal hematoma (RE) is a rare occurrence. A case of RE in a 48-year-old man who suffered a whiplash trauma in a motor vehicle accident is reported. He had been receiving long-term aspirin therapy for ischemic heart disease. Management consisted on tracheostomy and medical treatment and the patient evolved satisfactorily. Whiplash injuries that take place in predisposed subjects can originate RE. Diagnosis is made by X-ray and CT. If acute airway obstruction occurs it is safer to perform tracheostomy than endotracheal intubation. If the lesion is non-expanding, medical treatment is preferred by most authors, so do we. PMID- 7873244 TI - [Relative size of the ventricle to the hemisphere in the neonatal MRI]. AB - Using a software program for measuring surface area, we quantified the relative size of four parts of the lateral ventricles, including the body, the trigone, the anterior horn and the occipital horn, compared to the hemispheres in the axial plane of magnetic resonance imaging (MRI) in neonates. In 44 neonates without any neurological disorders from 26 to 41 weeks of gestational age (GA), MRI was performed between 12 and 124 postnatal days. The mean of the relative size of the ventricle compared to the hemisphere (RSVH) among the subjects showed a significant left-right asymmetry that was observed only in the occipital horn. However, in the body, the anterior horn and the occipital horn, the percentage of neonates with a larger left RSVH compared to the right RSVH was significantly higher than the percentage of neonates with a larger right RSVH compared to the left RSVH. The RSVH of the body and the occipital horn increased according to the number of postnatal days and decreased according to GA. Measuring RSVH was useful in assessing the size of the ventricle in the axial plane of neonatal MRI. It clarified the fact that normative asymmetry, GA of subject, and the number of postnatal days should be considered in assessing the size of ventricle. PMID- 7873243 TI - [Hypoglossal nerve paralysis after intubation and direct laryngoscopy]. AB - We described an extremely uncommon case of hypoglossal nerve paralysis occurred after a direct laryngoscopy under general anesthesia with McIntosh's laryngoscope intubation. We reviewed the literature on similar cases and studied the etiology and pathogenesis of these paralyses. PMID- 7873245 TI - [Brain CT studies in 26 cases of aged patients with Down syndrome]. AB - Computed tomographic images of brains from 26 individuals (10 males and 16 females) with Down syndrome were analysed for roentogenographic measurement. Their ages ranged from 14 to 47 years, the average being 28 years. The results showed that their Sylvian fissure ratio was larger in the aged group. A high incidence of calcification in basal ganglia, choroid plexus and pineal body was noted (85%). An increased Sylvian fissure ratio and a high incidence of intracranial calcification may be practically used as representatives of premature aging. Furthermore, a high incidence of mega cisterna magna implicates that it is worthy of study whether individuals with Down syndrome have a predisposition to underdevelopment of cerebellum. PMID- 7873246 TI - [Global environmental and child neurology]. PMID- 7873247 TI - [Exacerbation of seizures by carbamazepine in four children with symptomatic localization related epilepsy]. AB - We treated one hundred and seventy-eight epileptic children with carbamazepine (CBZ) for eight years. Among them, four children with symptomatic localization related epilepsy, aged 11 months to 12 years, developed exacerbation of seizures. Their epilepsies were associated with hypoxic ischemic encephalopathy, head injury and ectopic gray matter. Despite the serum levels of CBZ (7.0 approximately 9.5 micrograms/ml) being within the therapeutic range, all of them had more frequent and severe partial seizures than before taking CBZ and one developed new atonic seizures. Diffuse irregular spike-wave complexes appeared on EEG in two children. Following discontinuation of CBZ in addition to replacement with phenytoin, their seizures became well-controlled and EEG findings improved except for residual focal spikes. Although CBZ is a widely used and effective antiepileptic drug for partial seizures, it should be kept in mind that CBZ may exacerbate seizures in children with symptomatic localization-related epilepsy. PMID- 7873248 TI - [Status epilepticus in two patients with Sotos syndrome]. AB - Two patients with Sotos syndrome showed very intractable and prolonged status epilepticus, resulting in poor outcomes. Clinical seizures and EEG abnormalities in patients with Sotos syndrome are sometimes noted, but they are usually mild. These two patients showed hypoplasia of corpus callosum on MRI. We considered the mechanism of intractable seizures, and emphasized the importance of careful management for their seizures and EEG abnormalities. PMID- 7873249 TI - [Mechanism on formation of new ipsilateral corticospinal tract following neonatal unilateral cortical ablation in rats]. AB - The corticospinal tract in the rat after neonatal ablation of the unilateral cerebral cortex was studied morphologically using the antegrade horse-radish peroxidase (HRP) tracing method. An aberrant ipsilateral tract was observed 7 days after the operation. Formation of the aberrant neuronal pathway has been confirmed to be contributed mainly by new axons, which ramified at the level of the pyramidal decussation from healthy corticospinal fibers. This ramified axon ran toward the ipsilateral dorsal funiculus. A few fibers also contributed to the aberrant pathway by changing their direction on the way of extension at the level of the pyramidal decussation. These results indicate that the ramification and change of the direction of extending axons play an important role for formation of a new ipsilateral corticospinal tract. PMID- 7873250 TI - [A boy with Emery-Dreifuss muscular dystrophy]. AB - We reported a 12-year-old boy with Emery-Dreifuss muscular dystrophy (EMD). He was born after uncomplicated full term pregnancy and delivery. There was neither consanguinity nor a history of neuromuscular disorders or cardiac diseases in his family. He walked at 14 months. Toe walking was recognized at age 5 years. Examination at age 12 years showed the following. He could walk and climb stairs. There was no Gowers' sign. He had mild weakness of muscles except for face muscles. He had joint contractures at heels, elbows and knees. Deep tendon reflexes could not be elicited. Serum creatine kinase activity was significantly raised. Electromyography showed a myogenic pattern. Muscle biopsy from the left quadriceps showed mild dystrophic changes. 24 h Holter monitoring showed atrioventricular block with Wenckebach phenomenon. Prognosis in EMD is strongly connected with cardiac involvement. Therefore, we must follow up this case carefully for cardiac symptoms. PMID- 7873251 TI - [A case of acute idiopathic pandysautonomia with SIADH]. AB - We reported a 6-year-old girl with acute idiopathic pandysautonomia (AIPD) associated with syndrome of inappropriate secretion of anti-diuretic hormone (SIADH). She showed various symptoms indicating the impairment of widespread sympathetic and parasympathetic nervous functions and SIADH, which followed common cold. Sural nerve biopsy showed severe reduction of both myelinated and unmyelinated fibers. The main site of the lesion of AIPD has been assumed to be the peripheral autonomic nervous system. However, there are a few reports indicating the involvement of the central nervous system in AIPD. The present case also indicates the involvement of hypothalamus in addition to the peripheral autonomic nervous system. PMID- 7873252 TI - [An autopsy case of Down syndrome in an adult patient with multiple senile plaques and systemic amyloidosis]. AB - A rare adult autopsy case of Down syndrome was reported. The patient was a 36 year-old male, whose chromosome analysis revealed 47, XY, +21. He showed typical systemic AA-amyloidosis and numerous senile plaques in the brain. Senile plaques were diffuse or primitive. They were composed of beta-protein, but negative for Congo-red stain. There were few neurofibrillary changes in the para hippocampal gyri. Nucleus basalis Meynert showed no significant lesion. The distribution of these plaques had some characteristics different from that for Alzheimer's disease. In the brain involvement of systemic AA-amyloidosis was restricted to the regions devoid of blood-brain-barrier, such as choroid plexus and pituitary gland. Cerebral beta-amyloid and systemic amyloid A protein were segregated on each side of the blood-brain-barrier. Therefore, we suggested that each amyloid might be synthesized and deposited by its own mechanism. Electronmicroscopically Hirano's body was identified in the hippocampal gyri. PMID- 7873253 TI - [A case of severe Becker muscular dystrophy diagnosed in early childhood- correlation between clinical severity and dystrophin testing]. AB - Since the 14kb human Duchenne muscular dystrophy (DMD) cDNA was cloned and its protein product "dystrophin" was discovered, immunochemical, biochemical and genetic analyses of dystrophin (dystrophin testing) have provided an accurate diagnosis of DMD/Becker muscular dystrophy in the clinical field. We performed dystrophin testing for a 5-year-old boy and confirmed he had severe BMD. Multiplex PCR of the DMD gene showed in-frame type deletion from exon 45 to 48. Immunohistochemical analysis of the muscle specimen obtained from the patient showed a discontinuous and patchy staining pattern, using monoclonal antibody that recognizes the C-terminus domain of dystrophin. On immunoblot analysis, we detected a faint band of 390 kDa. Dystrophin quantity was less than 10% of that compared to normal controls. The correlation between clinical severity and dystrophin testing was discussed. PMID- 7873254 TI - [Investigation of seriously handicapped children with intensive medical cares in Tokyo]. PMID- 7873256 TI - [High amplitude somatosensory evoked potentials in a case of severe myoclonic epilepsy in infancy (SMEI)]. PMID- 7873255 TI - [A case of protein losing enteropathy due to carbamazepine]. PMID- 7873257 TI - [Therapeutic trial for circadian rhythm disturbance in two severely handicapped patients]. PMID- 7873258 TI - [Excitatory psychic symptoms induced by zonisamide in six cases of brain damages]. PMID- 7873259 TI - [Esophageal carcinosarcoma: morphologic and cytometric study]. AB - Carcinosarcoma of the esophagus is a rare malignant neoplasm composed by both carcinomatous (epithelial) and sarcomatous (mesodermal) elements. We report a case, diagnosed by biopsy an endoscopic brushing. Cytometric analysis was also performed. PMID- 7873260 TI - [Physiological reflux in proximal esophagus (assessment with simultaneous pH monitoring in proximal and distal esophagus in healthy subjects]. AB - Two-level pH monitoring was performed for 24 hours in 20 healthy subjects to document the presence of reflux episodes and to obtain reference values for reflux studies. The pH probes were placed 5 and 20 centimetres above the LES by means of a manometric technique. Significant differences were found at these two levels. At the proximal esophageal level 18 of the 20 subjects had reflux episodes. Five centrimetres above the lower esphageal sphincter the total reflux time was 1.35%, 2.05% in the upright and 0.15% in the supine positions. At 20 centimetres level it was significantly lower: 0.5% the total percent time with pH below 4, 0.8% and 0% in the upright and supine positions respectively. The mean reflux time was about 40% of the distal value, but the same pattern of reflux was observed at two levels of the esophagus. This technique is useful in documenting the cephalad extend of GER and allows to identify normal GER patterns at different levels of the esophagus. PMID- 7873261 TI - [Omeprazole and cimetidine in the treatment of upper digestive hemorrhage]. AB - AIM: To compare the efficacy of omeprazole (40 mgs/12 h i.v.) and cimetidine (1,200 mgs/i.v./day) in the management of upper gastrointestinal bleeding. EXPERIMENTAL DESIGN: Randomized, prospective open clinical trial. The end points are: mortality, surgical requirements, transfusion requirements, and length of hospitalization in Bleeding Unit and Hospital. PATIENTS: We study patients with upper gastrointestinal bleeding from peptic sources (duodenal ulcer, gastriculcer, acute gastric erosions and peptic esophagitis). 462 patients are evaluated and 282 finally included. RESULTS: 151 patients were given cimetidine and 131 omeprazole. No significant differences in any of the end points were found. CONCLUSIONS: The use of omeprazole does not improve cimetidine efficacy in the entire group of patients with upper gastrointestinal bleeding. PMID- 7873262 TI - [Role of extended type R2 lymphadenectomy in the surgical treatment of resectable gastric cancer]. AB - The extended lymphadenectomy has been proposed as routine procedure in the surgical treatment of gastric cancer, although some controversies have been published. We present a retrospective analysis on the impact of extended lymph node dissection after total gastrectomy, in terms of post-operative course and histopathologic findings, in a group of 30 patients with R2 lymphadenectomy and in 16 patients with R1 lymphadenectomy. There were no significant differences in duration of operation, amount of blood transfusion and length of hospital stay between the 2 groups. The only significant difference was found in the greater amount of drainage output after R2 lymphadenectomy as compared with R1. There were no mortalities in either group and morbidity rate was similar for both [43% in R1 and 40% in R2) mostly in the form of abdominal infections (18% in R1 and 16% in R2]). A significantly greater number of lymph nodes was identified after R2 gastrectomy. Fifty-three per cent of patients has positive lymph nodes, 12% of them being from the N2 echelon of nodes (including one case of early gastric cancer). Careful lymph node dissection in gastric cancer surgery allows a more precise staging of the tumor with no increase in postoperative morbidity. PMID- 7873263 TI - [Liver involvement in Q fever and Mediterranean boutonneuse fever. Comparative study]. AB - Rickettsia spp. infections produce hepatic damage with transaminases elevation and biological signs of cholostasis. Classical biochemical tests of hepatic function were analyzed and compared in 8 patients with Q Fever (QF) and 7 with Boutonneuse Mediterranean Fever (BMF). Liver enlargement was detected in 75% of the QF group of patients as compared with the 57% of the BMF group. Transaminases were raised in 75% of the patients of the QF group and in 85, 7% of the BMF patients. Only one patient in the QF group showed manifest clinical jaundice. Statistically significant differences were found between the values of AST, ALT, alkaline phosphatase and GGT, which were higher in the QF group. Liver involvement is more important in patients with QF than in FBM. There is a large percentage of clinically silent involvement in both diseases. Liver function tests should be carried out in infections by Rickettsia spp. PMID- 7873264 TI - [Prevention of ischemic injury in hepatocellular transplant in the rat]. AB - The aim of this study was to evaluate the efficacy of certain antioxidant and/or hepatotrophic drugs on the sensitivity to ischemia of hepatocytes implanted into the spleen. Twenty four hours after hepatocellular transplantation, animals were submitted to 15 minutes of normotermic ischemia followed by 70% hepatectomy. Hepatocytic function was assessed 24 h later by measuring the intensity of the regenerative response, both in the liver and in the spleen. All drugs increased the percentage of regenerating hepatocytes, but only allopurinol and cyclosporine achieved significance. However none of the drugs were useful for hepatocytes implanted in the spleen, allopurinol having a deleterious effect. PMID- 7873265 TI - [Diversion colitis]. PMID- 7873266 TI - [Training in diagnostic and therapeutic ERCP]. AB - Training in diagnostic and therapeutic endoscopic retrograde cholangiopancreatography procedures is difficult and tedious. Currently, there is no consensus on how to plan and put it into practice. We believe that training in these procedures must be included in the training program of the gastroenterology resident, since the efficiency of these methods (both diagnostic and therapeutic) in biliopancreatic disease including their clinical, social and economic benefits are beyond doubt. Training in diagnostic endoscopic retrograde cholangiopancreatography should be planned for about 3 months including at least 100 procedures under supervision of an experienced endoscopist; on the other hand, training in the therapeutic aspects needs, in our opinion, a longer period, perhaps and additional 3 to 6 month period, although this goal is difficult to achieve in the 4-year program of a gastroenterology resident. A frequent performance of the techniques is required to acquire competence. In this paper, we emphasize the ideal conditions that, must be fulfilled to achieve an appropriate training in the diagnostic and therapeutic aspects of endoscopic retrograde cholangiopancreatography. PMID- 7873267 TI - [Autoimmune hemolytic anemia, infrequent complication of ulcerative colitis]. AB - Autoimmune hemolytic anemia is a rare complication of ulcerative colitis. A retrospective review of the cases of ulcerative colitis treated at our hospital between January 1984 and August 1993 showed that, among 210 patients, three presented autoimmune hemolytic anemia with a positive direct Coomb's test. They were two men and one woman suffering from a moderately active ulcerative colitis that affected the left colon. The hemolysis was diagnosed before the onset of colitis in two cases and after it in the other. In the only patient treated with sulphasalazine, this drug was stopped without improvement. All the patients were treated with steroids, with resolution of the anemia in one of them. Healing was achieved with splenectomy in the other two. Colectomy was not necessary in any case. After suppression of sulphasalazine and treatment with steroids, the next therapeutic option in patients with ulcerative colitis and autoimmune hemolytic anemia should be splenectomy, whereas colectomy should be only used with unresponsive patients, as well as with those affected by severe ulcerative colitis refractory to steroids. In patients presenting with ulcerative colitis and anemia, the possibility of autoimmune hemolytic anemia has to be considered since--in spite of being rare--it is responsive to proper treatment. PMID- 7873268 TI - [Chylous ascites secondary to liver cirrhosis]. AB - We report two cases of chylous ascites secondary to liver cirrhosis. The ascites in cirrohotic patients has chylous characteristics in only the 0.5-1.3% of cases. Its physiopathology is unknown. It is difficult of manage as is almost always refractory to diuretic treatment. In view of its short-term high mortality, liver transplantation should be considered in selected cirrhotic patients who develop spontaneous chylous ascites. PMID- 7873269 TI - [Cholestasis caused by Fasciola hepatica]. AB - Human infestation with Fasciola hepatica is observed occasionally. Cholestasis due to parasitic obstruction of the common duct is an infrequent complication. A case of fascioliasis is described in a 56 year-old male with symptoms of biliary colic and biochemical cholestasis. The diagnosis was based on the indirect hemagglutination test and the evidence of Fasciola hepatica in the extrahepatic biliary tract shown by ultrasound and ERCP. The patient presented an acute pancreatic reaction during an attempt at therapeutic endoscopic sphincterotomy. Medical treatment was initiated then with Bithionol. Cholestasis as well as the parasitosis were eliminated. Recovery was demonstrated by the normality of the titres of hemagglutination and of the biliary tract by ERCP. PMID- 7873270 TI - [Massive pseudocysto-jejunal hemorrhage caused by rupture of pseudoaneurysm of the splenic artery]. AB - The authors report a case of massive intestinal hemorrhage caused by rupture of a splenic artery pseudoaneurysm into a pseudocystojejunostomy. The pathologic and clinical features of this unusual complication of pancreatitis are discussed. One hundred and seventy one cases of major bleeding associated with pseudocysts and/or pseudoaneurysms have been reported in the literature during the period 1989-May 1991. Acute and chronic pancreatitis may be the underlying etiologies and the overall mortality rate of this complication is 35.1%. According to the authors experience, angiographic localization of the bleeding sources and steel coil embolization play a key role in the diagnostic and therapeutic approach to what is generally regarded as the most rapidly lethal sequelae of pancreatitis. PMID- 7873271 TI - [Massive hemoptysis as the onset of pancreatico-bronchial fistula]. AB - OBJECTIVE: A fistula between the pancreas and the bronchial tree is a rare manifestation of pancreatic disease. PATIENTS: We describe a case of a pancreatic pseudocyst that penetrated into the thoracic cavity through the diaphragm, and set up a communication with the bronchial tree developing an episode of massive haemoptysis. PMID- 7873272 TI - [Pathologic rupture of the spleen caused by infectious mononucleosis]. PMID- 7873273 TI - [Jejunal adenocarcinoma]. PMID- 7873274 TI - [Internal Ophthalmoplegia--diagnostic tests and clinical application]. PMID- 7873275 TI - [Breakdown of the blood-brain barrier and clearance of extravasated proteins after experimental brain injury]. AB - It is well recognized that extravasation of circulating proteins is contributed to the formation of vasogenic brain edema after traumatic brain injury. However, clearance of the extravasated proteins from brain tissue remains unclear. In the present study we therefore identified the clearance procedure by evaluating extravascular localization of endogenous serum albumin and exogenous protein tracer, horseradish peroxidase (HRP), after experimental brain injury in rats. Adult male Wistar rats were subjected to a lateral fluid percussive injury. In study 1, HRP was given intravenously 10 minutes before sacrifice. Animals were sacrificed at 1, 2, 24, 72 hours and 7 days after injury in order to determine re establishment of the blood-brain barrier. In study 2 extravascular accumulation of serum albumin and HRP given before impact was examined at 1, 6, 24, 72 hours and 7 days after injury to evaluate the clearance of these extravasated proteins. Localization of each protein was assessed in injured brain sections at the microscopic level. In study 1, breakdown of the blood-brain barrier was noted in various regions of the injured brain at 1 hour. This barrier disruption was restored in almost regions by 2 hours. Impact site, however, remained permeable upto 72 hours. In study 2, the distribution of extravasated proteins was similar between albumin and HRP at 1 hour post-injury. Pronounced extravasation of both proteins occurred in discrete regions through the injured brain. After 6 hours post-injury a differential accumulation was noted between albumin and HRP. The diffuse extracellular accumulation of albumin was most widespread at 24 hours and less intense at 72 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873276 TI - [Immunohistochemistry using antibody to the glucose transporter 3 in human brainstem and cerebellar tissues]. AB - The localization of the glucose transporter 3 (GLUT3) was examined immunohistochemically, using a newly developed polyclonal antibody, in human brainstem and cerebellar tissues from neurologically normal, lacunar stroke and Alzheimer disease cases. In the brainstem, GLUT3 immunoreactivity was limited to the melanized neurons of the paranigral nucleus and substantia nigra, and to neurons in dorsal nucleus of the vagus nerve, and in the oculomotor, pontine, ambigius and hypoglossal nuclei. In the cerebellum, only the dentate nucleus had positive immunoreactivity. Glial cells and endothelial cells were not immunopositive. The results suggest a preferential expression of GLUT3 in particular neurons with a differential glucose need. PMID- 7873277 TI - [Protective effects of KC-764 on short-term forebrain ischemia in gerbils]. AB - KC-764, developed as a cyclo-oxygenase inhibitor, was administered to gerbils in a dose of 10 mg/kg, i.p., before subjecting them to 5-minute bilateral forebrain ischemia in order to determine whether it would have any protective effects. No post-ischemic hyperthermia (over 39 degrees C for 120 min) was observed in the KC 764 group. Behavior recovery time after ischemia was 11.4 +/- 2.8 minutes in the KC-764 group versus 87.3 +/- 13.4 minutes in the control group (p < 0.05). Delayed neuronal death (DND) in the CA1 region of the hippocampus was inhibited in the KC-764 group, but when the KC-764-treated animals were exposed to hyperthermia, the degree of DND was the same as in the control group. EEG voltage recovery time in the CA1 region of the hippocampus was almost the same in the control group, the KC-764 group, and the KC-764-plus-hyperthermia (HT) group. Although tissue blood flow measurements in the CA1 region of the hippocampus showed post-ischemic hypoperfusion (81 +/- 18% of the pre-ischemic level at 60 minutes), it was prevented in the KC-764 group (102 +/- 21%) (p < 0.05) and the KC-764-plus-HT group (96 +/- 28%). There was a tremendous increase in PGD2 (1461.4 +/- 863.4 p mol/g) and PGF2 alpha (219.6 +/- 104.2 p mol/g) in the forebrain after 5 minutes of reflow, but this increase in prostaglandin levels was inhibited (p < 0.05) in the KC-764 group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873278 TI - [Differential diagnosis between recurrence of gliomas and radiation necrosis by 201TlCl SPECT]. AB - We studied the value of quantitative 201Thallium Chloride brain SPECT (Tl SPECT) in the differentiation between glioma recurrence and radiation necrosis. A total of 44 patients--26 patients with recurrent malignant glioma, 10 patients with low grade glioma and 8 patients with radiation necrosis--underwent Tl SPECT. The patients had early SPECT images taken 15 minutes after intravenous injection of 3mCi of 201TlCl and also had delayed SPECT images taken 4 hours after injection. Count ratios of a lesion to normal brain (L/N) were calculated from the rectangular ROI for the quantitative analysis. Count ratios of the lesion seen on the delayed image to that on the early image (D/E) were also calculated. In 26 patients with recurrent malignant gliomas, L/N ratio ranged from 2.6 to 12.6 with a mean of 4.4 +/- 2.3 on early images. All patients had L/N ratios greater than 2.5. However, in 8 patients with cerebral radiation necrosis, L/N ratios ranged from 1.5 to 2.4 with a mean of 2.0 +/- 0.3 on early image. L/N ratios were always 2.5 or less. In 8 patients with cerebral radiation necrosis, there were little differences between the L/N ratios for early and delayed images. D/E ratios ranged from 1.0 to 1.3 with a mean of 1.2 +/- 0.1. These results confirmed the validity of Tl SPECT in differentiating cerebral radiation necrosis from recurrent malignant gliomas. In 10 patients with low grade astrocytoma there was a subtle uptake or no uptake of Tl and the ratios of these patients were rated at 1.0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873279 TI - [Estimation of neural generators of cognitive potential P300 by dipole tracing method]. AB - A computer-aided method dipole tracing system, allows to estimate the location of the generator of brain potentials and has the advantage of non-invasive recording in physiological state. In this experiment, a two-dipole model and a four-dipole model of the active electrical sources of the cognitive component P300 of event related potentials have been examined by using dipole tracing method in normal human subjects. We have recorded P300 in a group of 3 healthy females aged 19-24 years, using somatosensory stimuli requiring a button-press response. The brain potentials were recorded with 21 surface electrodes placed over the scalp. Three dimensional coordinates of surface electrodes and scalp, skull and brain (SSB) geometry of the subjects were measured by special device and three-dimensional MRI images, respectively. In order to estimate the localization of active dipoles, the conductivities of the scalp, the skull and the brain were approximated to be 1: 1/80: 1. In the present study, with data derived from all 21 channels, the sources of individual P300 components were analyzed during 10-30 msec at every 1 msec intervals. As a result, the dipole locations for each subjects were similar both in the two dipole model and in the four dipole model. The calculation on two dipole model showed the generators of P300 situated symmetrically in the frontal lobe. Whereas, the calculation on four dipole model showed them situated symmetrically near the hippocampus and in the parietal cortex which were close to the neural generators of P300 reported by other authors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873280 TI - [Werner's syndrome associated with meningioma and a cerebrovascular disorder]. AB - We present a case of Werner's syndrome associated with intracranial meningioma and a cerebrovascular disorder. A 49-year-old male was transferred to this hospital with a head injury as a result of a car accident, and a CT scan revealed a traumatic intracerebral hemorrhage. The patient displayed the characteristic clinical features of Werner's syndrome, including premature senility, juvenile cataract, atrophic skin, and a tendency to ward familial occurrence was present. MRI and cerebral angiography revealed multiple intracerebral hemorrhages, perhaps due to amyloid angiopathy, multiple lacunar infarctions and parasagittal meningioma. This is the first report on the MRI findings in the brain of a patient with Werner's syndrome. We suspect that of Werner's syndrome also shows evidence of premature aging on MR images. PMID- 7873281 TI - [Two cases of distal superior cerebellar artery aneurysm]. AB - Two cases of subarachnoid hemorrhage due to a ruptured aneurysm of the distal superior cerebellar artery (SCA) are reported. In the first case the patient was a 78-year-old woman who complained of severe headaches and was admitted to a local hospital on May 25, 1992. A CT scan revealed a subarachnoid hemorrhage, and an angiogram showed an aneurysm of the right ambient segment of the superior cerebellar artery. Trapping of the aneurysm was successfully performed via a subtemporal approach on June 9, 1992. In the second case the patient was a 46 year-old man who complained of severe headaches and was admitted to Kurume University Hospital. A CT scan showed subarachnoid hemorrhage and an angiogram showed an aneurysm of the right ambient segment of superior cerebellar artery. Trapping of the aneurysm was successfully performed via a subtemporal approach on Sept 11, 1990. Forty-three reported cases of distal SCA aneurysm were reviewed. Only one patient received early surgical treatment, and with surgery in all of the other cases being delayed. Both of our patients underwent delayed surgical treatment with excellent results. The clinical characteristics of distal SCA aneurysms and the timing of surgery are discussed. PMID- 7873282 TI - [Autosomal dominant spinocerebellar degeneration with pigmentary retinopathy in a Japanese family]. AB - We report a pedigree of autosomal dominant spinocerebellar degeneration associated with pigmental retinopathy. The proband is a 75-year-old man. He noticed night blindness at the age of 10 years and a diagnosis of bilateral pigmentary retinopathy was made at age 63. At the age of 65 years, he developed dysarthria and difficulty in walking. At age 69, neurological examination revealed cerebellar signs, and brain CT scans showed mild atrophy of the brain stem and cerebellum. Repeated brain CT scans revealed slight progression of the brain stem and cerebellar atrophy. Molecular genetic studies showed the absence of any mitochondrial DNA mutation at 8993. The father of the proband exhibited cerebellar signs and pigmentary retinopathy. One older brother had cerebellar signs and another had pigmentary retinopathy. To our knowledge, hereditary spinocerebellar degeneration with retinal degeneration is rare in Japan. This study is the first full report on hereditary spinocerebellar degeneration with pigmentary retinopathy in Japan, although an abstract was published by Konishi et al. We also discuss the neuropathological discordance on hereditary olivoponto cerebellar atrophy with retinal degeneration. PMID- 7873283 TI - [Longitudinal analysis of glucose metabolism in recurrent meningioma]. AB - We repeatedly measured kinetic rate constants and glucose metabolic rate (kinetic rCMRG1) using dynamic positron emission tomography (PET) and autoradiographic rCMRG1 in a patient with recurrent meningioma. A 50-year-old woman who presented with a left visual disturbance was admitted to our hospital. MR images revealed a mass lesion occupying the left middle fossa. The patient underwent Simpson grade IV surgery. The histological diagnosis was meningothelial meningioma. One year later the tumor had grown back to almost the same size as before treatment and was removed again by Simpson grade IV procedure. Postoperatively, the patient underwent radiation therapy (54 Gy). Two years after the second operation, the tumor was found to have invaded the left orbit and was resected by Simpson grade IV procedure. After additional radiation therapy, the patient was discharged. The rate constants were analyzed preoperatively and whenever the tumor recurred according to the three compartment 18F-fluorodeoxyglucose (FDG) model. Preoperative PET indicated tumor k1 and k2 values higher than in the contralateral gray matter, suggesting high permeability due to absence of the blood-tumor barrier and an abundant blood supply. The tumor k3 value, an indicator of hexokinase activity, was as high as in the contralateral gray matter. When the tumor recurred, the tumor k1, k2 and k3 values remained consistently high, indicating high proliferative activity. In contrast, the contralateral gray matter k1, k2 and k3 values decreased to some extent, suggesting effects of surgery or radiotherapy. Tumor rCMRG1 values, both autoradiographic and kinetic, were enhanced markedly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873284 TI - [Vitreous hemorrhage after accidental head injury with chest compression--case report]. AB - Vitreous hemorrhage is relatively common following subarachnoid hemorrhage, but rarely occurs after accidental head injury. In this paper, we report a rare case of vitreous hemorrhage after an accidental head injury with chest compression. A 4-month-old girl was held in her father's arms. After he fell down, she struck her head and her chest was compressed by her father's body. She soon became pale and was immediately transported to our center complaining of disturbance of consciousness on February 6, 1993. On admission, she was semicomatose and had a generalized convulsion. Computed tomography (CT) scan showed a subdural hematoma, although no fracture was detected on the plain X-ray film. Bilateral vitreous hemorrhage was also observed. The anterior fontanelle pressure was a high 330 mmH2O. The patient was treated conservatively with agents to promote hemostasis and reduce the intracranial hypertension. She was discharged after one month with normal consciousness and improved vision. The follow-up CT scan revealed subdural hematoma, hemorrhagic infarction (suggesting rupture of the pontine veins), and cerebral atrophy, corresponding to those of the shaken baby syndrome. Her chest was compressed by her father's body. The anterior fontanelle pressure was a high 330 mmH2O. These findings suggest that shaking or abrupt deceleration, acute intrathoracic hypertension and acute intracranial hypertension, caused retinal hemorrhage, and that extensive retinal hemorrhage possibly resulted in vitreous hemorrhage. PMID- 7873285 TI - [A 65-year-old woman with headache, facial pain, and progressive multiple cranial neuropathy]. AB - We report a 65-year-old woman with progressive multiple cranial neuropathy. She had been suffered from bronchial asthma since 1979 for which prednisolone had been prescribed. She noted an onset of pain around her nose in October, 1989, which extended into the periorbital regions bilaterally. In February, 1990, she was treated with stellate ganglion block and trigeminal nerve block; these treatments partially alleviated her pain. In May of 1991, she noted a difficulty in swallowing solid foods. In November of the same year, she developed right facial paresis; two weeks later, she noted numbness in her left face, and was hospitalized to our service on December 16, 1991. On admission, she was afebrile and general physical examination was unremarkable except for piping rales in her both lung fields. On neurologic examination, she was alert and oriented to all spheres; higher cerebral functions were intact. In the cranial nerves, her olfactory sense was lost bilaterally; her vision was markedly diminished bilaterally only to recognize hand movements; the optic fundi appeared normal; the pupils were isocoric and reacted to light promptly. The extraocular muscles were moderately weak to most of the directions more on the left; no nystagmus was present. Facial sensation was diminished bilaterally; the jaw deviated to right; right facial paresis of peripheral type was present; her hearing was diminished bilaterally more on the right. The movement of the soft palate was diminished on the right side; dysphagia was present; her voice was horse; the gag reflex was diminished. The sternocleidomastoid muscle was weak bilaterally; the tongue appeared normal. Examination of gait was differed because of headache, however, no apparent motor weakness was present. No ataxia or involuntary movement was noted. Deep reflexes were normally elicited and symmetric. Plantar response was flexor. Sensation in the extremities was intact. Kernig's sign was positive at 70 degree leg extension; eyeball tenderness was also present bilaterally, however, no nuchal stiffness was noted. Following abnormalities were present in the laboratory examination: WBC 11,400/microliters, ESR 50 mm/hr, CRP 6.1 mg/dl. The lumbar CSF was under a normal pressure containing 29 WBC/microliters (neutrophils 7, lymphocytes 20, others 2), 67 mg/dl of protein, and 53 mg/dl of sugar; cultures for acid-fast bacilli as well as for other bacteria were negative; no malignant cells were found. A cranial CT scan revealed an isodensity mass in the orbit and ill-defined low density areas in the white matters of the frontal lobes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7873286 TI - Are MG-63 and HOS TE85 human osteosarcoma cell lines representative models of the osteoblastic phenotype? AB - The aim of this study was to perform a systematic comparison of two widely used osteosarcoma cell lines and ascertain their relevance as experimental models for investigating osteoblast function. We have therefore compared growth, differentiated cell function, integrin expression and adhesive profiles of MG-63, HOS TE85, and human bone derived cells. Both osteosarcoma cell lines proliferated more rapidly than osteoblast-like cells with HOS cells exhibiting the shortest doubling time. HOS cells expressed higher levels of alkaline phosphatase than MG 63 cells under basal conditions but only MG-63 cells showed the increased enzyme activity following 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) administration, which is characteristic of bone derived cells. Osteocalcin was not detected in supernatants from any cells under basal conditions but levels produced by MG-63 cells on addition of 1,25(OH)2D3 were comparable with those of osteoblast-like cells. alpha 1, alpha 2, alpha 3, alpha 5, alpha V, and beta 1 integrin subunits were detected on all cells and there was no staining for alpha L, alpha M, beta 2, and beta 3. alpha 3 and beta 1 were the major subunits detected on MG-63, HOS, and bone derived cells but relative concentrations of other alpha subunits were dependent on cell type; alpha 4 and alpha 6 subunits could only be detected on osteosarcoma cell lines. Short term, serum-free cell adhesion assays showed that the three cell types adhered in a saturable manner to collagen I, fibronectin, and laminin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873287 TI - Age-dependent morphometric change in the lumbar vertebrae of male and female rats: comparison with the femur. AB - The morphological parameters, bone area, marrow area, bone-to-bone+marrow ratio, periosteal-to-total bone surface ratio, and surface-to-volume ratio, were studied in the fourth and fifth lumbar vertebrae of male and female rats (Heiligenberg strain) between birth and the end of lifespan. With increasing age, the bone area and marrow area increased for all ages, whereas the bone-to-bone + marrow ratio, periosteal-to-total bone surface ratio, and surface-to volume ratio decreased during the first 150 days. Afterwards, the bone-to-bone + marrow ratio decreased, whereas the periosteal-to-total bone surface ratio and surface-to-volume ratio were nearly constant. Modelling data were measured by use of the vital labeling technique with calcein. From the stained bone area the bone formation and the bone resorption rates were calculated. The bone formation rate, about 8300%/year, was highest after birth and decreases continuously with increasing age to 14%/year. The bone resorption rate, about 1100%/year, was highest after birth and decreased continuously with increasing age to 9%/year, whereas for all ages the bone formation rate was higher than the bone resorption rate, which led to an increase in bone area. The values obtained for the lumbar vertebra are compared with literature data and with the corresponding data for the distal femur obtained under identical conditions. PMID- 7873288 TI - The response of rat tibiae to incremental bouts of mechanical loading: a quantum concept for bone formation. AB - To investigate the minimum number of loading bouts necessary to produce new lamellar or woven bone formation, and the time required for its initiation, bone formation was measured in 32 retired breeder female Sprague-Dawley rats following one, two, three, or five bouts of applied loading. Bending forces of 54 N were applied to right tibiae using a four-point loading apparatus, and left tibiae served as contralateral controls. Loading was applied as a sine wave with a frequency of 2 Hz for 18 s (36 cycles) per loading bout. Rats were injected with alizarin on day 1 and calcein on days 5 and 12, and were killed on day 19. One bout of loading was sufficient to increase the periosteal woven bone surface (Wb.Pm/B.Pm) from 0% to 40% (p < 0.01), and to 80% after five bouts of loading (p < 0.01), with a dose-response relationship for increases in Wb.Pm/B.Pm (p < 0.0001), mineral apposition rate (Wb.AR; p = 0.002), and bone formation rate (Wb.BFR/BS; p = 0.0001). In the first labeling period (days 1-5), the endocortical lamellar bone forming surface (BSf/BS) was increased slightly (p < 0.05), but no significant differences were shown for BFR/BS or MAR. From days 5 to 19, right tibiae showed a dose-response increase in BFR/BS (p = 0.002) and BSf/BS (p = 0.008), but not MAR. These results are consistent with a "quantum" model of bone formation such that a "quantum" of bone cells is activated in response to the loading bout and the strain magnitude dictate the size or microstructural organization of a given packet of new bone. Conversely, the distributed nature of loading may define the recruitment, rather than size, of new packets of bone. PMID- 7873289 TI - An ultrastructural, microanalytical, and spectroscopic study of bone from a transgenic mouse with a COL1.A1 pro-alpha-1 mutation. AB - A line of transgenic mice have been investigated that expressed moderate levels of an internally deleted human gene for the pro alpha (I) chain of type I procollagen. These mice expressed the gene at approximately 50% that of the endogenous gene. The gene construct was modeled after a sporadic in-frame deletion of the human gene that produced a lethal variant of osteogenesis imperfecta by causing biosynthesis of shortened pro alpha (I) chains. Periera et al. (1993) reported extensive fracturing in these mice with femurs that were shorter in length and bone that had decreased ash weight, mineral, and collagen content. These workers demonstrated an increased brittleness in bone using biomechanical measurements. The functional consequences of these mutant genes were examined in both transgenic and in normal littermate mice to determine if a valid model at the ultrastructural and analytical level had been produced for OI. X-ray microanalysis of bone mineral demonstrated a significantly lower calcium-to phosphorus (Ca/P) molar ratio in transgenic mouse bone than in normal littermates; this was a feature of human OI bone. Fourier transform infrared spectroscopy confirmed that the mineral present was apatitic in nature despite the lower Ca/P molar ratio. Alizarin red skeletal staining showed the presence of multiple fracture calluses on the ribs and on the long bones of some of the transgenic mice, this was not seen on normal littermates. No light microscopic differences were observed between normal and transgenic mice; however, many ultrastructural correlates with human OI were observed in the transmission electron microscope. Anomalous fibrils associated with type I collagen, and an amorphous calcified material was observed lining the cartilage, extending beyond the lamina limitans in young transgenic mice. PMID- 7873290 TI - Bone mineral density in asthmatic women on high-dose inhaled beclomethasone dipropionate. AB - Inhaled corticosteroids are the cornerstone of the modern therapy for asthma. In recent years, inhaled corticosteroids have been used in higher doses than previously. This has caused concern about possible osteoporotic side-effects. We studied bone mineral densities (BMDs) in 19 non-smoking women (mean age 53 years, range 40-63) with newly diagnosed bronchial asthma and 19 voluntary healthy non smoking women (mean age 53 years, range 43-67). In both groups, 13 subjects were postmenopausal. Patients started beclomethasone dipropionate from the spacer 500 micrograms twice daily as the sole corticosteroid therapy. BMDs were measured with dual-energy x-ray absorptiometry (DEXA) at the lumbar spine (L2-4) and at the left proximal femur (the neck, Ward's triangle and the trochanteric region). The measurements were made at baseline and 6 and 12 months thereafter. No significant changes were observed in the measured BMDs in either study group. The results show that inhaled beclomethasone dipropionate therapy 1000 micrograms/day for one year does not affect BMD. Further studies are needed to assess the effects of inhaled corticosteroid on BMD during a longer treatment period. PMID- 7873291 TI - Skeletal growth and bone density as sensitive parameters in experimental arthritis: effect of cyclosporin A. AB - Osteopenia and retarded skeletal growth are consistent features of juvenile polyarthritis. Although the former has also been described in the experimental animal, the consequences of induced joint inflammation on skeletal growth have not yet been documented. In order to investigate the effect of experimental arthritis on these parameters, we studied female rats with adjuvant arthritis (AA) subjected to chronic treatment with cyclosporin A (CsA, Sandimmun). This compound has been found to prevent the development of articular swelling and also repair joint and skeletal lesions in AA rats. Five groups of 8 animals each received oral CsA, 2.5, 5, 10, 20, or 30 mg/kg daily for 30 days. Eight normal and eight diseased, untreated rats served as placebo controls. The parameters studied were (a) measurement of hindpaw swelling, (b) radiometric assessment of vertebral growth, (c) vertebral trabecular density, (d) weight control and nutritional status. At the end of the investigational period, AA-rats on no therapy had severe osteopenia and growth retardation. Treatment with CsA, 2.5 mg/kg, was ineffective, but doses between 5 and 20 mg/kg prevented the development of articular and osseous lesions and normalized growth. A catch-up phenomenon was also observed. The 20 mg/kg dose showed no better effect than 10 mg/kg, and 30 mg/kg produced a significant reduction in bone density and skeletal growth, an effect thought to be toxic in nature. Body weight paralleled growth profiles, and average food consumption was stable in all groups with the exception of somewhat low records in the animals receiving 30 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873292 TI - Effects of osteocytes on osteoinduction in the autogenous rib graft in the rat mandible. AB - In order to clarify the influence of cell death of osteocytes on osteoinduction after bone grafting, autogenous fresh ribs, bone-marrow-removed fresh ribs, and frozen devitalized ribs were grafted after removal of the periosteum in a bridge manner in the rat mandible, and the process of bone remodeling was studied histologically, histochemically, and ultrastructurally in the central portion of the grafts. In the fresh bone group, osteocytes maintained normal morphology and grafted bones were undergoing resorption by osteoclasts with ruffled borders and strong tartrate-resistant acid phosphatase (TRACP) activity on the fifth day (Day 5). Alkalinephosphatase (ALP)-positive osteoblast-like cells were observed in close proximity of the osteoclasts. On Days 7 to 9, new bone formation occasionally accompanied by newly formed cartilage was observed in the grafted bones, and by Day 14, the majority of the grafted bones had been replaced by newly formed bone. In the marrow-removed fresh bone group, bone resorption by TRACP-positive cells and new bone formation similar to those seen in the fresh bone group were observed on Day 10. In the frozen devitalized bone group in which osteocytes had undergone necrosis, bone resorption and new bone formation were not observed even on Day 84, and grafted bones became surrounded by fibrous tissues. The TRACP activity was very weak and no ruffled border was observed ultrastructurally in multinucleated giant cells seen on Day 14. In conclusion, immediate bone resorption by osteocytes is essential for osteoinduction in the bone graft, and living osteocytes in the graft play an important roll in the differentiation and activation of osteocytes. PMID- 7873293 TI - In vivo and in vitro effects of insulin-like growth factor-I (IGF-I) on femoral mRNA expression in old rats. AB - The in vivo response of bone to IGF-I infusion in a marrow ablation model and the effect of IGF-I on bone marrow stromal cells in vitro was evaluated. IGF-I (25 ng/day), infused directly into femur, stimulated the expression of alkaline phosphatase, procollagen alpha 1 (I) and osteopontin mRNA, while osteocalcin mRNA was not affected. The dose dependency to IGF-I was bi-phasic, with stimulation at 25 and 50 ng but not at 150 ng/day. The effect of IGF-I was observed in the aged but not in the adult rat femur. However, the elevated mRNA levels in old bones with IGF-I treatment were still below those observed in adult bones. The effect of IGF-I was also examined in cultured stromal cells. IGF-I (50 ng/ml) stimulates the expression of alkaline phosphatase, procollagen alpha 1 (I), osteopontin and osteocalcin mRNA in stromal cells from both adult and old rats. These results suggest that the lack of response of adult bone to IGF-I in vivo was not due to the impaired response of the stromal cells to IGF-I. Differences in the responses of stromal cells from adult and old animals were noted. In the presence of serum (10%), stromal cells from adult rats were stimulated to synthesize DNA at lower levels of IGF-I than stromal cells from old animals. Our results show that IGF-I can stimulate mRNA expression of osteoblast markers in vivo in aged rats in a marrow ablation model and enhance DNA synthesis and gene expression in cultured marrow stromal cells from old rats. Thus, it is possible that exogenous IGF-I could be beneficial in treating age-associated osteopenia. PMID- 7873294 TI - Stochastic simulation of vertebral trabecular bone remodeling. AB - Bone remodeling changes bone mass, architecture, and thereby bone strength, during normal aging. These changes seem to be accelerated during the menopause. Several therapeutic agents have been used in order to delay the onset of the menopause-related changes. The effects of these agents on the remodeling process have been determined histomorphometrically in several short-term clinical studies, but data from long-term clinical studies are difficult to achieve, as are data on the influence on bone strength. The aim of this study was to develop a computer stimulation model that could assist in predicting the long-term effects of changes in the remodeling process on bone mass, trabecular thickness, and perforations. The paper presents such a stochastic model of the remodeling process in human vertebral trabecular bone. The computer model is based on histomorphometric and structural data from human studies. It is presented in terms of flow charts, and simulations performed with the model are discussed in relation to measurements on human vertebral bone samples. The results show that a menopause-related doubling of the activation frequency causes a transient, mainly reversible bone loss. If the menopause is accompanied by an increase in both activation frequency and resorption depth, then the resulting bone loss will be more pronounced and with a larger part being irreversible bone loss (perforations). The two antiresorptive agents. Etidronate and estrogen both cause a slight increase in bone mass (reducing remodeling space), and Etidronate also seems capable of preventing perforations. During fluoride therapy, an initial increase in remodeling space followed by a reduction is seen. Very few perforations are found to take place during fluoride therapy. The present model has been validated by assessing the effects of the menopause and treatment with antiresorptive or anabolic agents. It was found that the results mirrored or anabolic agents. It was found that the results mirrored very closely the results (bone mass measurements) from short-term clinical studies. It is therefore concluded that the model provides a tool for evaluating existing and new therapeutic regimens. PMID- 7873295 TI - Switching from DXA pencil-beam to fan-beam. I: Studies in vitro at four centers. AB - The performance of the Hologic QDR-2000 DXA osteodensitometer was critically evaluated at four centers, using at all four centers one bone equivalent humanoid spine phantom supplied by the manufacturer. Results were compared with results from Hologic QDR-1000/W using that phantom tested at the same centers. It appears that the concept of fan-beam scanning--as used in the QDR-2000: a fan-beam, a linear array detector above the phantom, and an x-ray tube located rather close to the spine below the phantom--creates problems due to the magnification effect of the fan beam. The effect of decreasing the distance between the "vertebrae" of the phantom and the couch are: bone mineral content (BMC) increases by 2.8% per cm, projected area (Area) by 2.8% per cm, and bone mineral density (BMD) is unchanged. When QDR-1000/W is upgraded to QDR-2000, BMD is relatively constant, but there are shifts of BMC and Area which are partly due to the magnification effect of the fan-beam. Replacement of a QDR-1000/W with a QDR-2000 can invalidate longitudinal measurements, even for BMD, unless the proportionality factors of the QDR-2000 are checked and, if necessary, changed. This is true for switching from QDR-1000/W to pencil-beam mode of QDR-2000 or to fan-beam mode of QDR-2000. Even with pencil-beam mode, the long-term precision error with phantoms is higher for QDR-2000 than for QDR-1000/W (for BMD, 0.47% versus 0.35%). PMID- 7873296 TI - Switching from DXA pencil-beam to fan-beam. II: Studies in vivo. AB - Switching from the Hologic QDR-1000/W to the QDR-2000 DXA densitometer was critically evaluated with regard to cross-calibration and dosimetry. Studies with bone equivalent humanoid spine phantoms and patient studies were done. Fan-beam scanning with the QDR-2000 is problematic because of magnification. Mean phantom bone mineral content (BMC) and bone mineral density (BMD) were moderately but significantly different. Biological variation disguised differences between the two devices in humans, but significant differences were revealed when individual data were analyzed. Longitudinal assessments of BMC and BMD, initiated with QDR 1000/W and continued with the QDR-2000, should employ single-beam mode only and not fan-beam mode--but even if that is done, significant errors can be introduced. The new QDR-2000 should be properly cross-calibrated with the original densitometer, and one should make sure that the same software, phantom, and type of collimator are used. The radiation dose is substantially higher with QDR-2000 (fan-beam and high-resolution array mode) than with QDR-1000/W (pencil beam mode) and QDR-2000 (pencil-beam mode), and higher than claimed by the manufacturer. The typical radiation dose given by the manufacturer was half the actual radiation dose measured (e.g., for fan-beam scan 62 microSv versus 33 microSv). High-resolution array mode does not improve precision, but augments the radiation dose to the patient. PMID- 7873298 TI - Hypermineralized lamellae below the bone surface: a quantitative microradiographic study. AB - Hypermineralized lamellae similar to interstitial resting lines were identified by microradiography beneath haversian, endocortical, and trabecular resting surfaces in 42 subjects aged 18-96 years. In cross-sectioned osteons, this hypermineralized lamella appeared as a circle showing the same high microdensity as the inner margin of the haversian canal. Bone tissue separating this circle and the margin was more mineralized than the peripheral lamellae of the osteon. In the tibia, 13.7 +/- 0.9% (Mean +/- SE) of Haversian canals exhibited a hypermineralized circle, localized at a distance of 20 +/- 0.4 microns from the canal wall. The scalloped haversian canals, different from osteoclastic resorption cavities, represented 9.9 +/- 0.7% of the haversian canals. There was a significant correlation between both types of haversian canals. Therefore, hypermineralized lamellae can appear at the end of bone apposition, whatever the bone surface. Their high mineral content may secondarily lead to an increased brittleness of the most superficial lamellae and even to their disaggregation. PMID- 7873297 TI - Effect of phosphate supplementation on the expression of the mutant phenotype in murine X-linked hypophosphatemic rickets. AB - The X-linked Hyp mouse, a murine homologue of X-linked hypophosphatemia in humans, is characterized by rachitic bone disease, hypophosphatemia, impaired renal brush-border membrane Na(+)-phosphate cotransport and abnormal regulation of renal vitamin D metabolism. We demonstrated that short-term phosphate supplementation decreases renal 1,25-dihydroxyvitamin D3 (1,25-(OH)2D) catabolism and increases serum 1,25-(OH)2D levels in Hyp mice (Tenenhouse & Jones 1990). In the present study, we compared several other parameters in normal and Hyp mice fed control (1%) and high (1.6%) phosphate diets for 4 days. Phosphate supplementation significantly raised serum phosphate levels and decreased renal brush-border membrane Na(+)-phosphate but not Na(+)-glucose, cotransport in both genotypes (67% of control diet, p < 0.05). However, under both dietary conditions, the phosphate/glucose transport ratio was significantly reduced in Hyp mice (58% of normal littermates, p < 0.05). Renal PTH-stimulated cAMP accumulation, which was significantly blunted in Hyp mice compared to normal mice under control dietary conditions (p < 0.05), was not altered by phosphate supplementation in either genotype. Serum alkaline phosphatase activity was significantly higher than normal in Hyp mice on the control diet and was further increased in mutants but not in normals fed the high phosphate diet (p < 0.05). Measurements of serum bilirubin and electrophoresis of serum alkaline phosphatase suggested that the elevation in serum alkaline phosphatase activity in phosphate supplemented Hyp mice represents the bone-derived isozyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873299 TI - Effect of slow-release sodium fluoride on cancellous bone histology and connectivity in osteoporosis. AB - We have previously demonstrated that a treatment regimen of slow-release sodium fluoride (SRNaF) and continuous calcium citrate increases lumbar bone mass, improves cancellous bone material quality, and significantly reduces vertebral fracture rate in osteoporotic patients. In order to assess whether such treatment also improves trabecular structure, we quantitated cancellous bone connectivity before and following 2 years of therapy with SRNaF in 23 patients with osteoporosis and vertebral fractures. In addition, we performed bone histomorphometry on the same sections used for connectivity measurements. There was a significant increase in L2-L4 bone mineral density during therapy (0.827 +/ 0.176 g/cm2 SD to 0.872 +/- 0.166, p = 0.0004). Significant histomorphometric changes were represented by increases in mineral apposition rate (0.6 +/- 0.4 microns/d to 1.1 +/- 0.7, p = 0.0078) and adjusted apposition rate (0.4 +/- 0.3 microns/d to 0.6 +/- 0.4, p = 0.016). On the other hand, trabecular spacing significantly declined (from 1375 +/- 878 microns to 1052 +/- 541, p = 0.05). Two dimensional quantitation of trabecular struts on iliac crest histological sections disclosed significant increases in mean node number per mm2 of cancellous tissue area (0.22 +/- 0.12 vs. 0.39 +/- 0.27, p = 0.0077), the mean node to free-end ratio (0.23 +/- 0.21 vs. 0.41 +/- 0.46, p < 0.05), and in the mean node to node strut length per mm2 of cancellous area (0.098 +/- 0.101 vs. 0.212 +/- 0.183, p < 0.01). There were no significant changes in any of the measurements associated with free-end number or free-end to free-end strut length.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873300 TI - Effect of clodronate on fracture healing in denervated rats. AB - The effect of clodronate on healing of the fracture of osteopenic bone was studied in rats. A total of 165 female rats (14 +/- 1 weeks, 216 +/- 2 g) were divided into five fracture groups (n = 30), and a neurectomized group (n = 15). Osteopenia (op) was induced by right sciatic neurectomy 4 weeks before the fracture. Nonosteopenic (nop) rats were not operated. A closed prepinned diaphyseal fracture of the right femur was done by three-point bending method both to op and nop rats, and the left femur served as an unoperated control. All the fracture groups were divided into treatment (clodronate 10 mg/kg/day sc) and control (saline sc) groups, and the administration was continued throughout the study. The op rats were killed 2, 4, 8, and 12 weeks and nop rats 8 weeks after the fracture. Fracture healing was examined by x-ray and bone-bending strength. Neurectomy reduced bone strength (p < 0.01) at 4 weeks. Clodronate did not affect the bending strength of healing callus of op rats at 2, 4, 8, or 12 weeks after fracture, but reduced the strength of healing callus in nop rats (p < 0.05) at 8 weeks. Radiologic callus width increased in clodronate-treated groups both in op (8 and 12 weeks, p < 0.001) and nop rats (8 weeks, p < 0.05) when compared with saline-treated groups. Clodronate did not affect normal bone strength. In conclusion, clodronate did not affect the bending strength of op fracture nor the strength of the control bones. The remodeling of the fracture was delayed with clodronate. PMID- 7873301 TI - Neonatal reductions in osteoclast number and function account for the transient nature of osteopetrosis in the rat mutation microphthalmia blanc (mib). AB - We have examined the general and skeletal manifestations of osteopetrosis in a new, mild osteopetrotic mutation in the rat, microphalmia blanc (mib). Newborn mutant (mib) rats exhibit the typical skeletal deformities and sclerosis of osteopetrosis at birth, which are reduced significantly during the first postnatal month but don't disappear entirely up to 8 months later. Osteoclast numbers, staining for TRAP and TraATPase, and bone resorption are reduced in mutants during the first 2 postnatal weeks but improve by 1 month. In mutants, serum concentrations of calcium and phosphorus are normal, but 1,25(OH)2 D levels are higher at 1 week than those in normal littermates. Neonatally, mutants exhibit extramedullary hemopoiesis in the spleen. These results are interpreted to mean that the transient perinatal skeletal sclerosis in mib rats is caused by reduced production and function of osteoclasts in this period. The recent description of transient, perinatal osteopetrosis in a child suggests that analyses of the early differences between mild and severe animal mutations might distinguish those children with osteopetrosis who need treatment from those who do not. PMID- 7873302 TI - Increased bone formation by intermittent parathyroid hormone administration is due to the stimulation of proliferation and differentiation of osteoprogenitor cells in bone marrow. AB - In order to examine the mechanism of the anabolic effect of parathyroid hormone (PTH) on bone formation, human PTH(1-34) [hPTH(1-34)] (30 micrograms/kg) was injected subcutaneously to 9-week-old rats 5 times a week for 1 or 3 weeks. Trabecular bone volume (BV/TV) in the tibial metaphysis was not significantly different between the PTH- and vehicle-treated groups, but the parameters related to bone formation, including osteoid surface (OS/BS), mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS), were significantly increased as early as 1 week after PTH treatment. And the parameters related to bone resorption including eroded surface (ES/BS) and osteoclast number (N.Oc/BS) were also significantly increased as early as 1 week after PTH treatment. Treatment with PTH for 1 week induced no significant increase in bone mineral density at the femoral metaphysis, whereas the same treatment for 3 weeks induced a significant increase. When bone marrow cells isolated from femora and tibiae of either PTH- or vehicle-treated rats were cultured at a high density (2 x 10(7) cells/one well of 24-multiwell plate), cellular alkaline phosphatase (ALP) activity was significantly increased in the cells isolated from PTH-treated rats compared with vehicle-treated rats. When bone marrow cells were cultured at a low density (4 x 10(6) cells/a one well of 6 multiwell plate) to generate colonies (colony forming unit-fibroblastic, CFU-F), PTH induced apparent increases in both the total number of CFU-F and the number of ALP-positive CFU-F.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873303 TI - A survey of job stress and job satisfaction among DSAs in the north-west of England. AB - This study was a survey of job stress and job satisfaction among DSAs in general practice in the north-west of England during 1993. The results suggest that severe overall job stress and dissatisfaction were not prevalent but do present an important problem for a minority. The chief sources of stress are ranked. Those which caused moderate to severe stress were: running behind time, feeling under-valued by the dentist and handling difficult patients. Those experiencing greater stress outside work were more likely to report stress within it. Having a regular staff meeting, an annual salary review and a clear job description were associated with significantly less job stress. PMID- 7873304 TI - Hepatitis B vaccination: knowledge among clinical dental staff and students in Dundee. AB - It is now generally acknowledged that all health care workers should be vaccinated against hepatitis B. To this end, a questionnaire was sent to 132 clinical dental students and 70 staff in August 1993 at a British dental hospital, to assess their vaccination status. Approximately 10% of subjects had not completed their course of immunisation. Furthermore a significant number of subjects had failed to follow up their vaccination by an antibody titre test. Our results suggest that approximately 1 in 7 cases failed to seroconvert, emphasising that mere vaccination may not offer sufficient protection against hepatitis B. Thus adequate cross-infection control measures must be maintained in the interest of all patients. PMID- 7873305 TI - Resolution of lichen planus following removal of amalgam restorations in patients with proven allergy to mercury salts: a pilot study. AB - Thirteen patients with symptomatic oral lichen planus had been shown by patch testing to be allergic to ammoniated mercuric chloride. Replacement of amalgam restorations in these patients effected an improvement in all but one case. In some cases the resolution of symptoms was dramatic following the replacement of one or two fillings. The authors feel that the removal of all amalgam fillings need not be necessary except in the most intractable case. PMID- 7873306 TI - Clinical decision making--an art or a science? Part II: Making sense of treatment decisions. AB - Clinical decisions made by dentists can vary considerably. Although there has been a tendency in the media to attribute these differences between practitioners to deliberate unethical practice, as Part I concluded, variations in decision making are a result of the complexity of assessing the risks of different treatment options and evaluating the outcomes of treatment. This article looks at why dentists can make different decisions when faced with identical cases (variation), why sometimes the 'correct' decision is not made (error), and also looks at what other issues affect treatment decision making once disease has been perceived. PMID- 7873307 TI - The other side of Australia. PMID- 7873308 TI - Is the BDJ ready to go electronic? PMID- 7873309 TI - Severe anaphylactic reaction to latex rubber surgical gloves. PMID- 7873310 TI - Anaphylactic reactions to peanuts. PMID- 7873311 TI - Impacted third molars. PMID- 7873312 TI - Oral health and implanted joint prostheses. PMID- 7873313 TI - Topical antibiotics and gastric flora. PMID- 7873314 TI - Topical antibiotics and gastric flora. PMID- 7873315 TI - The hazards of chronic exposure to nitrous oxide: an update. AB - This paper reviews the potential occupational hazards associated with chronic exposure to nitrous oxide. The evidence that chronic exposure to the gas produces problems related to reproduction in dental personnel is convincing. Recent evidence suggests that scavenging systems decrease the adverse effects which nitrous oxide has on fertility of dental surgery assistants. However, even in the presence of scavenging systems trace levels of the gas can exceed recommended minimum levels. PMID- 7873316 TI - Natural history of hypertrophic cardiomyopathy. PMID- 7873318 TI - Electrophysiological investigation of patients with hypertrophic cardiomyopathy. Evidence that slowed intraventricular conduction is associated with an increased risk of sudden death. PMID- 7873317 TI - Risk factors and stratification for sudden cardiac death in patients with hypertrophic cardiomyopathy. PMID- 7873319 TI - Hypertrophic cardiomyopathy: an introduction to pathology and pathogenesis. PMID- 7873320 TI - Dilated cardiomyopathy: an introduction to pathology and pathogenesis. PMID- 7873321 TI - Link between enteroviruses and dilated cardiomyopathy: serological and molecular data. PMID- 7873322 TI - Role of autoimmunity in dilated cardiomyopathy. PMID- 7873323 TI - Familial dilated cardiomyopathy. PMID- 7873325 TI - Identification and management of the high risk patient with dilated cardiomyopathy. PMID- 7873324 TI - Multiple disease genes cause hypertrophic cardiomyopathy. PMID- 7873326 TI - Changing mortality in dilated cardiomyopathy. The Heart Muscle Disease Study Group. AB - OBJECTIVE: To analyse the changes in mortality in dilated cardiomyopathy over the past 15 years and to identify the factors that might have influenced survival. DESIGN: Follow up study of 235 patients (aged 16-70) systematically enrolled on a register from 1 January 1978 to 31 December 1992. SETTING: Hospital department of cardiology. PATIENTS: Three groups corresponding to three periods of 5 years: group 1 (diagnosis between 1 January 1978 and 31 December 1982) 26 patients; group 2 (diagnosis between 1 January 1983 and 31 December 1987) 65 patients; and group 3 (diagnosis between 1 January 1988 and 31 December 1992) 144 patients. MAIN OUTCOME MEASURES: Death or heart transplantation. RESULTS: Two and four year survival was 73.8% and 53.8% in group 1, 87.7% and 72.3% in group 2, and 90.3% and 82.9% in group 3 (P = 0.02). During the 15 years of the study period the number of cases increased progressively and the baseline clinical characteristics changed (that is, patients were younger and less severely affected), partly explaining the improvement in survival. None the less, the three mortality curves tended to diverge progressively and the improvement in survival in the different groups was still significant after stratification for the severity of the disease, suggesting that treatment had a sustained effect. A progressively higher proportion of patients were treated with angiotensin converting enzyme (ACE) inhibitors and more recently with beta blockers. In group 2, after stratification for the severity of heart failure, patients who were treated with ACE inhibitors showed a better survival than patients who were not. Furthermore, analysis of group 3 showed that beta blockers had a significant additive effect with conventional therapy both by intention to treat and actual treatment. Four year survival in patients with mild and moderate to severe heart failure treated with beta blockers, and usually digitalis and ACE inhibitors, was respectively 90% and 87.5%. CONCLUSIONS: The improvement in the survival of patients with dilated cardiomyopathy over the past 15 years may be explained by earlier diagnosis, new treatments, and a change in the clinical characteristics of the patients at enrolment. PMID- 7873328 TI - Special issue: Predictive modelling. PMID- 7873329 TI - Predictive microbiology. AB - Predictive microbiology is based upon the premise that the responses of populations of microorganisms to environmental factors are reproducible, and that by considering environments in terms of identifiable dominating constraints it is possible, from past observations, to predict the responses of those microorganisms. Proponents claim that predictive microbiology offers many benefits to the practice of food microbiology, and there is growing interest internationally. This review considers the origins, benefits and approaches to predictive microbiology and critically considers limitations and potential solutions. It is suggested that the traditional delineation between kinetic and probabilistic models is artificial, and that the two approaches represent the opposite ends of a spectrum of modelling needs. It is concluded: that despite the complexity of many food systems predictive modelling can be successfully applied; that strategies based on predictive models can simplify problems and allow useful predictions and analyses to be made; that the full potential of the technique has not yet been realised; and that "predictive microbiology" may be seen as providing a rational framework for understanding the microbial ecology of food. PMID- 7873327 TI - Treatment of end stage dilated cardiomyopathy. AB - Patients should be referred for cardiac transplantation only after all other means of management of congestive heart failure have been attempted and have been unsuccessful (table 3). An adequate therapeutic trial of conventional and experimental agents including beta blockade and vesnarinone should be completed and be shown to be unsuccessful before transplantation is considered in patients in NYHA class III. Prospective clinical trials need to be completed to define the role of newer therapeutic options. The scarcity of donor organs will probably preclude the use of cardiac transplantation in all patients who may benefit. Alternative methods of cardiac replacement (such as dynamic cardiomyoplasty, permanent implantable mechanical circulatory assistance, and xenografting) must be developed. These methods coupled with better pharmacological treatment will greatly improve the outcome of patients with dilated cardiomyopathy. PMID- 7873330 TI - Modelling the growth, survival and death of microorganisms in foods: the UK food micromodel approach. AB - Techniques for the development of mathematical models in the area of predictive microbiology have greatly improved recently, allowing better and more accurate descriptions of microbial responses to particular environmental conditions, thus enabling predictions of those responses to be made with greater confidence. Recognising the potential value of applying these techniques in the food industry, the Ministry of Agriculture, Fisheries and Food (MAFF) initiated a nationally coordinated five-year programme of research into the growth and survival of microorganisms in foods, with the aim of developing a computerised Predictive Microbiology Database in the UK. This initiative has resulted in the systematic generation of data, through protocols which ensure consistency of methodology, so that data in the database are truly comparable and compatible, and lead to reliable predictive models. The approaches taken by scientists involved in this programme are described and the various stages in the development of mathematical models summarized. It is hoped that this initiative and others being developed in the USA, Australia, Canada and other countries, will encourage a more integrated approach to food safety which will influence all stages of food production and, eventually, result in the development of an International Predictive Microbiology Database. PMID- 7873331 TI - A dynamic approach to predicting bacterial growth in food. AB - A new member of the family of growth models described by Baranyi et al. (1993a) is introduced in which the physiological state of the cells is represented by a single variable. The duration of lag is determined by the value of that variable at inoculation and by the post-inoculation environment. When the subculturing procedure is standardized, as occurs in laboratory experiments leading to models, the physiological state of the inoculum is relatively constant and independent of subsequent growth conditions. It is shown that, with cells with the same pre inoculation history, the product of the lag parameter and the maximum specific growth rate is a simple transformation of the initial physiological state. An important consequence is that it is sufficient to estimate this constant product and to determine how the environmental factors define the specific growth rate without modelling the environment dependence of the lag separately. Assuming that the specific growth rate follows the environmental changes instantaneously, the new model can also describe the bacterial growth in an environment where the factors, such as temperature, pH and aw, change with time. PMID- 7873332 TI - Modelling the combined effect of temperature and pH on the rate coefficient for bacterial growth. AB - An extension of a model of Davey (1989a) has been used to model data of Adams et al. (1991) describing the combined effect of temperature and pH on the rate coefficient for growth of Yersinia enterocolitica in liquid media acidified with four different acidulants: sulphuric, citric, lactic and acetic acids. The model explained between 97.8% and 99.1% of the variance in the results. This very good fit between the predictions and the observed data confirms pH can be incorporated into a model that had previously been applied to the combined effect of temperature and water activity, and to the effect of temperature alone. These findings, taken together with previously reported results, demonstrate the value of the model for predicting the combined effect of two environmental factors on the growth rate. Based on results reported in this paper and previously reported results, a generalised model is proposed for the combined effect of three or more environmental factors, that is amenable to testing. PMID- 7873333 TI - Predictive modelling: applications in the dairy industry. AB - Predictive modelling has been used in the dairy industry for determining the keeping quality of raw milk and pasteurized products. More recently, predictive equations describing growth and toxin production for a number of bacteria of concern to dairy microbiologists have been developed. A more mathematical approach is also being adopted for determining effective pasteurization conditions for organisms present in milk. PMID- 7873335 TI - Response surface model of the effect of pH, sodium chloride and sodium nitrite on growth of Yersinia enterocolitica at low temperatures. AB - A fractional factorial design was used to measure the effects and interactions of temperature (5, 12, 19 degrees C), pH (4.5-8.5), sodium chloride (0.5-5%) and sodium nitrite (0-200 micrograms/ml) on the aerobic growth of Y. enterocolitica in brain heart infusion broth. Growth curves were modeled by fitting plate count data to the Gompertz equation. Quadratic models of natural logarithm transformations of the Gompertz B and M values and the derived values for lag phase durations and generation times were obtained using response surface analysis. Predictions based on the models for B and M values were comparable to predictions based on the derived values. These models provide a means for rapidly estimating how the bacterium is likely to respond to any combination of the four variables within the specified ranges. PMID- 7873334 TI - Expansion of response surface models for the growth of Escherichia coli O157:H7 to include sodium nitrite as a variable. AB - The previously published (Buchanan et al., 1993a) response surface models for estimating the aerobic and anaerobic growth of Escherichia coli O157:H7 as a function of temperature, initial pH, and sodium chloride content have been expanded to include sodium nitrite as a further variable. A fractional factorial design was employed to quantitate the effect of NaNO2 in conjunction with the four other variables by culturing a three-strain mixture in brain heart infusion broth. The activity of NaNO2 was strongly pH-dependent, with inhibition being significant at pH values < or = 5.5 and enhanced by lowering the incubation temperature. The effects of the variables on Escherichia coli O157:H7 growth kinetics were modeled by response surface analysis using quadratic and cubic polynomial models of the natural logarithm transformation of both the Gompertz B and M parameters (Gompertz parameters) and the lag phase duration (LPD) and generation time (GT) values (kinetics parameters) calculated for individual growth curves. All models provided reasonable estimates for most variable combinations; however, comparisons of predicted versus observed values indicated that overall the most useful models were the cubic models based on LPD and GT values. Although additional validation of the models is required, comparisons of predicted times to a 1000-fold increase in population density against those calculated from previously published growth studies indicate that the models are an effective means for acquiring 'first estimates' of the growth characteristics of E. coli O157:H7. PMID- 7873336 TI - Model for the combined effects of temperature, initial pH, sodium chloride and sodium nitrite concentrations on anaerobic growth of Shigella flexneri. AB - A fractional factorial design was used to measure the effects and interactions of temperature (12-37 degrees C), initial pH (5.5-7.5), NaCl (0.5-4.0%) and NaNO2 (0 1000 ppm) on the anaerobic growth kinetics of Shigella flexneri in Brain-Heart Infusion broth. Anaerobic conditions were established by flushing the culture flasks with N2. A total of 375 cultures representing 124 variable combinations were analyzed, with growth curves being generated using the Gompertz equation. Growth rates decreased with decreasing temperature, decreasing pH and increasing NaCl level. NaNO2 in combination with low temperature, low pH and high NaCl content effectively inhibited S. flexneri. Response surface analysis was used to obtain models for estimating the growth of S. flexneri in terms of temperature, initial pH, and NaCl and NaNO2 concentrations. A third-order equation using the natural logarithm transformations for the Gompertz B and M terms gave reasonable estimates of bacterial growth in response to any combination of the variables studied within the specified ranges. PMID- 7873337 TI - An example of the stages in the development of a predictive mathematical model for microbial growth: the effects of NaCl, pH and temperature on the growth of Aeromonas hydrophila. AB - The stages involved in developing a predictive model are illustrated using data describing the effects of temperature (3-20 degrees C), NaCl concentration (0.5 4.5% w/v) and pH (4.6-7.0) on the aerobic growth of Aeromonas hydrophila (cocktail of 6 strains). Optical density measurements using micro-titre plates were used as an initial screen, to determine the appropriate sampling times for viable counts to be made and to determine the approximate boundaries for growth. Growth curves were generated from viable counts and fitted using a modified Gompertz equation. Quadratic response surface equations were fitted to the log of lag and generation times, in response to the variables of temperature, NaCl and pH (in terms of hydrogen ion concentration). The effects of various combinations of these controlling factors are described. Comparisons between predicted growth rates and lag times from our response surface equations and other models for growth of A. hydrophila, developed with viable count data and optical density measurements, are made, together with comparisons with data from the literature on the growth of this bacterium in foods. PMID- 7873338 TI - Growth of Listeria monocytogenes on vacuum-packed cooked meats: effects of pH, aw, nitrite and ascorbate. AB - Slices of cooked meats were inoculated with Listeria monocytogenes strain Murray B, vacuum-packed and stored at either 0 or 5 degrees C. Decreases in pH (6.9-5.9) and aw (0.993-0.960; adjusted with sodium chloride) of the cooked meats increased the lag time and reduced the growth rate at 5 degrees C. The type of meat (beef, pork, chicken or turkey) had no effect on the growth of the organism after allowance was made for pH. Sodium tripolyphosphate (0.3%) increased growth by increasing the pH of the cooked meat. Sodium nitrite reduced the growth rate and increased the lag time. Three microM of residual undissociated nitrite doubled the time taken for a 3 log increase in numbers of L. monocytogenes. The effectiveness of nitrite was significantly increased by sodium ascorbate (0.042%). In the absence of nitrite, ascorbate had no detectable effect on growth. The extent of growth at 0 degree C was similarly influenced by the interaction of pH, aw, nitrite and ascorbate, and was considerably less than at 5 degrees C. Quadratic equations were developed to describe some of the combined effects of pH, aw and residual nitrite on lag, growth rate and time for a 3 log increase in numbers of L. monocytogenes. PMID- 7873339 TI - Estimation of bacterial growth rates from turbidimetric and viable count data. AB - The relationship between maximum specific growth rates (mu max) determined from viable counts and turbidimetric measurements for a range of bacterial species is examined in order to assess the potential of turbidimetric methods in predictive microbiology. Two methods for the estimation of mu max from turbidimetric data are presented. One is based on absorbance and the other on transmittance measurements. Both are compared to estimates obtained by viable count methods. Calibration factors, a function to correct the non-linearity of absorbance measurements, and variance stabilising transformations for corrected absorbance measurements and for viable count data, are determined. It is concluded that turbidimetric measurements may be used reliably for estimation of mu max. PMID- 7873340 TI - Use of indirect conductimetry to predict the growth of spoilage yeasts, with special consideration of Zygosaccharomyces bailii. AB - In recent years, modeling for the purpose of predicting microbiological spoilage of foods has gained much interest. Predictive modeling requires a concentrated mathematical and experimental approach; to collect data of adequate quality is a technically demanding task when several experimental parameters are involved. Rapid, non-traditional, automated techniques are particularly useful in modeling. Of these, electrometric techniques appear to be most promising. Indirect conductimetry was used to study the effect of temperature, aw, pH and potassium sorbate concentration on the growth of Zygosaccharomyces bailii. The automated Malthus 2000 instrument proved to be convenient for gathering a large amount of data that were then used to develop polynomial models describing the response of the yeast to combinations of experimental factors in terms of conductimetric detection time and maximum rate of change in conductance. Results demonstrated that indirect conductimetry is suitable for monitoring the effect of environmental factors on the growth and activity of Z. bailii and perhaps other food spoilage yeasts. PMID- 7873341 TI - Predicting fungal growth: the effect of water activity on Aspergillus flavus and related species. AB - Growth of four species belonging to Aspergillus Section Flavi (A. flavus, A. oryzae, A. parasiticus and A. nomius) was studied at 30 degrees C at ten water activities (aw) between 0.995 and 0.810 adjusted with equal mixtures of glucose and fructose. Colony diameters were measured at intervals and plotted against time. A flexible growth model describing the change in colony diameter (mm) with respect to time was first fitted to the measured growth data and from the fitted curves the maximum colony growth rates were calculated. These values were then fitted with respect to aw to predict colony growth rates at any aw within the range tested. The optimum aw for each species and time to reach a colony diameter of 3 mm were also calculated. PMID- 7873342 TI - Mathematical modelling of the growth, survival and death of Yersinia enterocolitica. AB - This paper discusses the development of a novel mathematical equation capable of handling the growth, survival and death of microorganisms. The equation was used in combination with second-order polynomials to fit a response surface to data representing the growth, survival and death of Yersinia enterocolitica as affected by temperature (0-30 degrees C), sodium chloride (0-10.5% w/v), pH (3.5 7.0) and undissociated lactic acid (0-9.63 g/l). The resulting predictive model showed a good correlation over the entire range of the experimental data. Predictions from the model have been compared with independent data from both published literature and inoculated food studies. Analysis of the results showed a good correlation, particularly for data from milk and meat products. PMID- 7873343 TI - Modelling the destruction of Escherichia coli on the base of reaction kinetics. AB - Assuming that the inactivation of microorganisms is due to a chemical reaction between a 'critical structure' of the cell and another reactant molecule, mathematical models of the reaction rates can be applied to the process. Considering the stoichiometric equation of the chemical reaction, the thermal death or disinfection of microbes can be described by an extension of the Eyring's model. The extended model is applicable not only to heat inactivation, but also to disinfection kinetics and to the effect of pH. Taking into account the effect of the water activity on heat destruction, the extended model has been modified empirically and fitted to experimental data on the heat destruction of Escherichia coli. PMID- 7873344 TI - Modelling the thermal inactivation of Salmonella typhimurium using bioluminescence data. AB - Inactivation of micro-organisms by heat is a traditional food processing technique used to reduce or eliminate the microbial load in foods thus preventing bacterial associated disease and food spoilage. Models of thermal death kinetics are routinely used to predict the amount of heat required but such models are limited by the acquisition of accurate thermal death data for bacteria in situ and in complex microflora. In vivo bioluminescence from lux recombinant bacteria is an important alternative to traditional plate counts for examining bacterial injury and stress but the thermal instability of luciferase has appeared to preclude its application in heating studies. We have developed a procedure which overcomes the thermal instability of luciferase and demonstrate that computer generated models of the thermal injury of Salmonella typhimurium show equivalence between bioluminescence and viable count data. PMID- 7873345 TI - The current global situation of the HIV/AIDS pandemic. PMID- 7873346 TI - Expanded programme on immunization (EPI). Surveillance of EPI target diseases. PMID- 7873347 TI - Chagas disease. Interruption of transmission. PMID- 7873348 TI - Re-emergence of Bolivian haemorrhagic fever. PMID- 7873349 TI - Tuberculosis trends in central and eastern Europe and countries of the former USSR. PMID- 7873350 TI - Intestinal helminths. Anthelmintic drug trial. PMID- 7873351 TI - Food safety. Foodborne trematode infections. PMID- 7873352 TI - Influenza. PMID- 7873353 TI - Clinical applications of magnetic resonance spectroscopy. AB - Neurospectroscopy measures a neuronal marker, energy and redox state, specific fuels of tissue respiration, maturation, and possibly myelination. It provides diagnostic patterns of altered neurochemistry. Current clinical uses range from intensive care in neonates to dementia in the elderly and include tumor and stroke management, prognosis in hemorrhage and trauma, white matter, inflammatory diseases, and AIDS. Inborn errors, metabolic and systemic diseases, subclinical hepatic encephalopathy, hyponatremia, and "coma" have been elucidated. Automation, single-voxel MRS, chemical shift imaging, quality control, and outcome analyses are discussed. With no remaining impediments to clinical use, neurospectroscopy has changed the way we look at diseases of the brain. PMID- 7873354 TI - Concepts of myocardial perfusion imaging in magnetic resonance imaging. AB - Based on the major innovations in ultrafast magnetic resonance (MR) imaging in recent years, myocardial perfusion imaging with MR has become the focus of many investigators. Two major approaches to myocardial perfusion imaging involve either exogenous or endogenous contrast agents. For the first category of perfusion experiments, we review the characteristics of the common contrast agents and MR techniques for experimental and clinical first-pass studies and in particular address the question of extracting quantitative estimates for myocardial blood flow (milliliters per minute per gram) and volume (milliliters per gram). We demonstrated quantitative perfusion analysis using intravascular relaxation agents and heavily T1-weighted ultrafast gradient echo sequences. Signal time curves need to be transformed to content time curves and the resulting residue functions were analyzed with a multiple-pathway, axially distributed perfusion model. These preliminary results suggest that quantitative assessment of myocardial perfusion is feasible, but additional studies should provide further confidence for this novel MR approach. The exact sensitivity and specificity of MR first-pass imaging in conjunction with extracellular contrast agents in patient studies and its diagnostic accuracy as judged against coronary angiography and scintigraphic perfusion imaging remain yet undefined. The second category of perfusion experiments does not require exogenous contrast agents and has not yet been tested in patient studies. Progress is reported on several MR perfusion-sensitive methods that use the tissue water as an endogenous contrast agent in combination with magnetization transfer techniques as well as paramagnetic deoxyhemoglobin for measuring tissue oxygenation using heavily T2* weighted sequences for blood oxygen-level-dependent contrast. Possible future directions and developments toward further improvements for MR myocardial perfusion measurements and contraction-perfusion matching are also addressed. PMID- 7873355 TI - Classified information. PMID- 7873356 TI - First among equals. Interview by Kate Williams. PMID- 7873357 TI - NIH estates. Land for sale. PMID- 7873359 TI - Methods of nurse selection: a review. AB - The trauma and horror of the Beverley Allitt case, and others, have forced the issue of selection of prospective nurses back to the top of the agenda. In this article, the author criticises current selection procedures, then outlines some of the various psychological and intelligence tests which could, he claims, make selection a more objective and reliable process. PMID- 7873358 TI - NHS estates. Less than des. res. PMID- 7873360 TI - The Thorn nurse training initiative. AB - An innovative comprehensive diploma course has been devised for mental health nurses who are providing care for those suffering from serious mental illness. The course addresses the devolution of long term hospital care and is primarily clinically based. This article describes the background to the research carried out and recognises the importance of the course's development in the light of recent government legislation. In addition, it identifies how and why this innovative nurse training is now being disseminated to mental health nurses and highlights the importance of introducing this model of clinical work into routine community practice. PMID- 7873361 TI - Clinical audit: a tool for nursing practice. AB - Nurses are probably more aware of clinical audit now than at any time in history, but what do they actually know about it? Aware that for many, the words cause unnecessary fear and anxiety, the author has set out a simple guide to audit. The information in the article is based on a successful series of workshops on clinical audit she and her colleagues ran for nurses in the Greater Glasgow area. PMID- 7873362 TI - The management of dysphagia in stroke. AB - People who have strokes suffer a variety of problems, depending on the site and severity of brain damage. A particularly unpleasant and dangerous one is dysphagia which, if not properly assessed and managed, can prevent the patient receiving adequate nutrition to enable him or her to participate fully in a rigorous rehabilitation programme, or which may even cause his or her death through aspiration of food. The authors describe an appropriate nursing response to the problem, and advocate a multidisciplinary approach to the management of nutrition in the care of patients with strokes. PMID- 7873363 TI - Right to nurse. Practice makes perfect. PMID- 7873364 TI - Right to nurse. Your portfolio. PMID- 7873365 TI - Stringing us alone. PMID- 7873366 TI - All names please. PMID- 7873367 TI - Career breaks: get tough, get going. PMID- 7873368 TI - Buttercups and interviews. PMID- 7873370 TI - Higher education: too many chefs.... PMID- 7873369 TI - Patient's perspective: my way. PMID- 7873371 TI - Acquired haemophilia and its management. PMID- 7873372 TI - Effects of interleukin-6 on mobilization of primitive haemopoietic cells into the circulation. AB - Twenty-seven patients with advanced adenocarcinoma were studied. Groups of three patients received interleukin-6 (IL-6) in doses ranging from 0.5 to 20 micrograms/kg by daily subcutaneous injection on days 1-7 and 22-49. Four patients received IL-6 2.5 micrograms/kg/d with GM-CSF 5 micrograms/kg/d and three patients received IL-6 2.5 micrograms/kg/d with IL-3 5 micrograms/kg/d. Circulating platelet numbers increased 1.65-fold during IL-6 treatment, in a dose dependent fashion (P = 0.01). This increase is inferior to that expected from laboratory studies. No significant change in total WBC was seen after IL-6 alone. After treatment with IL-6, significant increases in numbers of circulating mononuclear cells (2.2-fold, P = 0.006) and GM-CFC numbers (3.2-fold, P = 0.01) were seen, but there were no changes in circulating megakaryocyte-CFC numbers. In contrast, after treatment with IL-6 and GM-CSF, larger increases in both circulating GM-CFC (20-fold, P = 0.04) and megakaryocyte-CFC numbers (18-fold, P = 0.03) were seen. Increases in blood progenitors after treatment with IL-6 and IL-3 did not achieve statistical significance. The ability of peripheral blood mononuclear cells to generate and sustain long-term haemopoiesis in vitro was similar in IL-6-treated patients to that in untreated control subjects. No significant changes in the incidence of bone marrow progenitors or their cycling status (assessed by thymidine suicide) were seen. These data suggest that IL-6 alone will not be clinically useful to mobilize blood progenitor cells in cancer patients. PMID- 7873373 TI - Diagnostic value of serum IL-6 level in monoclonal gammopathies. AB - The serum level of IL-6 was reported to reflect disease severity in patients with multiple myeloma. We used a specific radioimmunoassay to measure the level of IL 6 in 239 serum samples in which a monoclonal gammopathy was identified for the first time. The same sample was used for the measurement of serum C reactive protein and serum albumin. Then, an inventory of clinical and biological features allowed us to classify these patients into five groups: monoclonal gammopathy of undetermined significance (MGUS:128), multiple myeloma (MM:66), Waldenstrom's macroglobulinaemia (WM:27), non-Hodgkin's lymphoma (NHL:11) and chronic lymphocytic leukaemia (CLL:7). The number of patients with serum IL-6 (S-IL-6) level > 0.335 ng/ml (upper limit in normal sera) was significantly higher in the MM group (35%; Confidence Interval (CI) 23.5-46.5) compared with the MGUS group (15%; CI 8.8-21.2). The distribution of S-IL-6 levels was also significantly different between the groups (Mann-Whitney test: P < 0.01). High S-IL-6 levels were measured in 5/11 patients with NHL and 9/27 patients with WM. The distribution of S-IL-6 levels in these groups was the same as that in MGUS or MM groups. In patients with MM, elevated S-IL-6 levels were associated with haemoglobin level < 100 g/l (P < 0.005), bone marrow plasmocytosis > 50% (P < 0.005) and stages II and III in the Durie & Salmon staging system (P < 0.005). The S-IL-6 level was also related to light chain component excretion in urine (P < 0.01) and M component serum level for IgA (P < 0.01). In patients with MGUS, the S-IL-6 level correlated with serum CRP level (P < 0.05), serum lactate dehydrogenase (P < 0.05) and serum ferritin (P < 0.01). We conclude that the S-IL 6 level is a marker of high tumour burden in multiple myeloma. However, S-IL-6 level can be increased in patients with MGUS in relation to inflammatory parameters. Therefore the S-IL-6 level does not demonstrate high predictive value for the diagnosis of MM in patients with newly identified monoclonal gammopathy. PMID- 7873374 TI - Immunocytochemical and flow cytometric detection of proteinase 3 (myeloblastin) in normal and leukaemic myeloid cells. AB - Proteinase 3 (P3) is a serine proteinase present in the primary granules of neutrophils. We have investigated the expression of this protein in samples of bone marrow from healthy individuals and patients with different types of leukaemias by using immunocytochemical staining and flow cytometric quantitation. In normal bone marrow the enzyme was found in promyelocytes, myelocytes, metamyelocytes, band forms and polymorphonuclear neutrophils, correlating with the synthesis of neutrophil serine proteinases during myeloid maturation. No staining was found within the lymphoid, erythroid and megakaryocytic lineage. In the leukaemic samples, only those of acute myeloid and chronic myeloid leukaemia patients were labelled with the antiproteinase 3 antibody. Cases of acute lymphoblastic and chronic lymphocytic leukaemia, as well as other malignant lymphomas, were consistently negative, indicating that P3 may be used as a specific marker for the discrimination between myeloid and lymphoid leukaemias. In addition, immunoreactivity of myeloperoxidase (MPO) was investigated and the expression of P3 and MPO correlated with the French-American-British (FAB) classification. P3 was not detected in minimally differentiated M0 and M1 cases but was in predominantly labelled cells of M2 and M3 subtypes plus half of the M4 and one out of six M5 cases but not those of M6. These findings correspond to the differentiation stage in which P3 is expressed and stored in the primary granules. Therefore the enzyme may also be used as an adjunct to the classic morphological and cytochemical methods to elucidate further the stage at which the differentiation arrest of the leukaemic clone has occurred. PMID- 7873375 TI - Induction of differentiation into monocyte/macrophage cell lineage of a human eosinophilic leukaemia cell line EoL-1 by simultaneous stimulation with tumour necrosis factor-alpha and interferon-gamma. AB - Human myeloid leukaemia cell lines have been shown to differentiate into distinct cell lineages in vitro in response to several differentiation-inducing agents. A human eosinophilic leukaemia cell line, EoL-1, has been shown to differentiate into mature eosinophilic granulocytes by treatment with the culture supernatant of a human T-cell line, HIL-3. In this study we have studied whether the EoL-1 cell line has potential to differentiate into cell lineage other than eosinophils. We found that EoL-1 cells cultured in the presence of tumour necrosis factor (TNF)-alpha (10 u/ml) and interferon (IFN)-gamma (1000 u/ml) for 2-4 d differentiated into macrophage-like cells in morphology, and expressed CD14 antigen on their cell surface. It is possible that the small subpopulation of EoL 1 cells which contains non-specific esterase (NSE) activity may be preferentially differentiated by TNF-alpha and IFN-gamma. To clarify this issue, we have cloned the EoL-1 cell line and obtained NSE negative and positive sublines. Both EoL-1 sublines differentiated into monocyte/macrophage-like cells, because: (a) EoL-1 sublines were induced to express CD14 antigen, and (b) they attached firmly to the plastic wells; (c) after differentiation they became strongly positive for NSE staining, and secreted TNF-alpha in response to the stimulation with lipopolysaccharide; and (d) they exhibited potent phagocytic activity. Therefore, we found that the EoL-1 cell line has the ability to differentiate not only into mature eosinophilic cells but also into monocyte/macrophage cell lineage, suggesting that EoL-1 cells represent immature cells with ability to differentiate into multiple cell lineages. PMID- 7873376 TI - Erythropoietin gene expression in fetal and adult sheep kidney. AB - The exact location of the cells which express erythropoietin (Epo) in the kidney is still controversial, with conflicting reports suggesting that both peritubular interstitial cells or proximal tubular epithelial cells are possible sites of Epo expression. In the present study we have examined the location of Epo-expressing cells in fetal and adult sheep kidneys after Epo expression was stimulated by anaemia. In situ hybridization histochemistry was performed using synthetic oligonucleotide probes complementary to part of the sheep Epo cDNA sequence or a riboprobe (cRNA) for ovine Epo of 520 bases. Epo expression was confined to peritubular cells of the kidney cortex, in general in the area close to the cortico-medullary junction. In some severely anaemic adult sheep kidneys, Epo expressing cells were also found in the outer cortex. In addition we located Epo expressing cells in the kidneys not only of anaemic fetuses (89-140 d of gestation, term = 150d) but also in kidneys from normal fetuses 60-110d of gestation. Again, Epo expression was seen only in peritubular cells of the kidney cortex. These findings confirm that the kidney is an important site of Epo production, in the sheep, from at least 0.4 gestation, but also show that there is no ontogenic change in the cellular site of production within the kidney. PMID- 7873377 TI - Correlations between the intensity of fMLP-dependent respiratory burst and cellular fatty acid composition in human neutrophils. AB - The peripheral blood neutrophils were isolated from a group of normal subjects and their fatty acid composition determined by capillary gas-chromatography. The superoxide (O2-) release by the same cell preparation in response to formyl methionyl-leucyl-phenylalanine was also determined following cytochrome c reduction in a microplate assay. A strong negative correlation was found between C18:2 (linoleic acid) (r = 0.703, P = 0.001) and C:16:0 (palmitic acid) (r = 0.569, P = 0.009) and fMLP-stimulated O2- release, whereas C20:4 (arachidonic acid) correlated positively (r = 0.448, P = 0.048). Other fatty acids, namely C12:0, C14:0, C16:1, C18:1, C18:3, C18:4, C20:0, C20:1, C20:2, C20:5, C22:0, C22:1, C22:6, C24:0 and C26:0, were not correlated with O2-. No correlations were found between fatty acid composition and O2- release from resting cells and from cells stimulated by phorbol-myristate acetate. These results suggest that the fatty acid composition of blood neutrophils may be a critical factor determining the capability of releasing free radicals in response to formylpeptides. Moreover, since a concomitant increase of arachidonic acid and decrease of its precursor linoleic acid has been found in high-responsive neutrophils, the rate of the enzymes of the arachidonic acid biosynthetic pathway (elongases and desaturases) appear to play an important role. PMID- 7873378 TI - Immunomodulation treatment for childhood virus-associated haemophagocytic lymphohistiocytosis. AB - The Epstein-Barr virus (EBV), or human herpesvirus-6 (HHV-6) associated haemophagocytic lymphohistiocytosis, has been found prevalent in Taiwan; it affects previously healthy children and is always fatal when treated only supportively. Recognition of the underlying pathogenesis for this disease prompted adoption of an immunomodulatory regimen of intravenous immunoglobulin (IVIG) and/or etoposide on 17 such patients treated between 1990 and 1993. Remarkable improvement in patients' prognoses was demonstrated. Eight patients are still alive with a median follow-up of 1 year and 2 months post-treatment. Both IVIG and etoposide had positive immunomodulation effects such as alleviation of fever and normalization of haematological and hepatic parameters. Sustained complete response was obtained in two of nine cases of EBV-associated diseases treated with IVIG only. EBV transcripts became undetectable after etoposide and/or IVIG treatment without antiviral agents. Etoposide given by split-doses schedule appeared to be superior to conventional three-consecutive-days schedule for both remission induction and disease-free survival. Our preliminary trial apparently provides a promising improvement in the treatment of this previously fatal disease. IVIG or etoposide is effective in reversing the process of lymphohistiocytic dysregulation resulting from virus infection of immune cells in this syndrome and probably helps hosts to control active virus replication in certain cases, through immunomodulation. PMID- 7873379 TI - Efficacy of an analysis of lymphocyte subsets in predicting the clinical response to alpha-interferon therapy in thalassaemia patients with chronic infection by hepatitis C virus: a pilot study. AB - alpha-interferon (alpha-IFN) has been used to treat chronic non-A non-B hepatitis in thalassaemic patients with response rates from 45% to 83%. Unfortunately, treatment with alpha-IFN is associated with side-effects which have a negative effect on the quality of life of the patient. Therefore it would be useful if we could distinguish in advance those patients who would benefit from such therapy from those who would not. In the present study we found that the modification of lymphocyte subsets 20 h after the administration of the first dose of alpha-IFN revealed that relative numbers of T helper lymphocytes (CD4+) increased in three non-responding patients and decreased in five responding patients, whereas those of T suppressor lymphocytes (CD8+), and natural killer cells (CD57+, CD16+) decreased in non-responding patients and increased in responding patients. Therefore analysis of the lymphocyte subsets CD4, CD8, CD57 and CD16 before and 20 h after the administration of alpha-IFN can be used to predict the clinical response to treatment with alpha-IFN. PMID- 7873380 TI - A new Turkish type of beta-thalassaemia major with homozygosity for two non consecutive 7.6 kb deletions of the psi beta and beta genes and an intact delta gene. AB - In a 2.5-month-old infant with beta-thalassaemia major, DNA analysis of the gamma beta region revealed homozygosity for two large deletions removing the entire psi beta and beta regions including their 5' promoter regions but leaving the delta gene intact. The downstream deletion was predicted to be 7.6 kb in length extending from a point 1.5 kb on the 3' side of the delta-globin gene to about 1.8 kb on the 3' side of the beta-globin gene. The upstream deletion, which was also about 7.6 kb, extended from a point 1.5 kb on the 5' side of the psi beta globin gene to about 4.5 kb on the 3' of the psi beta gene. The delta-globin gene was intact. From the phenotypic expression of the disease it is concluded that removal of the psi beta gene probably prevents derepression of the gamma gene that has previously been observed in the absence of the promoter region of the beta gene and the switch mechanism from gamma to beta gene expression may take place earlier than expected. PMID- 7873381 TI - Long-term treatment with interferon-alpha 2b for severe pruritus in patients with polycythaemia vera. AB - Pruritus is a major clinical problem in patients with polycythaemia vera (PV). Conventional symptomatic treatment is unsatisfactory. Recently, a favourable effect of interferon-alpha on pruritus in patients with PV has been reported. Also, interferon-alpha suppresses the increased haemopoiesis in PV. However, long term treatment with interferon-alpha may be hampered by side-effects and the inconvenience of chronic subcutaneous injection therapy. We conducted a long-term study (median follow-up 13 months) of the efficacy and tolerability of interferon alpha in 15 patients (mean age 68 years) with PV and severe pruritus. Six patients were evaluable after 1 year. Pruritus significantly improved in 12/15 patients. Haematological control improved, as evidenced by a decreased number of phlebotomies from a mean of 4.3 in the year before the study to 1.8 while on interferon-alpha. Leucocyte and platelet numbers also decreased significantly. Five patients (33%) did not tolerate interferon-alpha. The effects of interferon alpha could not be ascribed to an inhibitive effect on histamine production or to the disappearance of the abnormal erythroid progenitor clone, because erythropoietin-independent erythroid colony formation persisted during interferon alpha treatment. We conclude that long-term interferon-alpha treatment is feasible and effectively relieves pruritus in patients with PV, but side-effects are an important concern. The optimal dose regimen that is well tolerated, relieves pruritus, and offers satisfactory haematological control at the same time remains to be established. PMID- 7873382 TI - The SCID mouse as a model for multiple myeloma. AB - The SCID mouse was investigated as a potential animal model for human multiple myeloma (MM). Duplicate samples of bone marrow mononuclear cells (BMMC) and/or peripheral blood mononuclear cells (PBMC) of six MM patients in different clinical phases and one patient with monoclonal gammapathy of undetermined significance (MGUS) were injected intraperitoneally into SCID mice. Human immunoglobulins (Ig) in the SCID sera were quantified with a light-chain isotype specific ELISA, and their monoclonality biochemically characterized, using a sensitive immunoblotting technique after agar gel electrophoresis. Successful transplantation of bone marrow derived-tumour cells in SCID mice was obtained with BMCC of two MM patients with progressive disease. Human plasma cells were detected in the mesenteric fat tissue around the pancreas and the spleen. This model in SCID mice may facilitate studies on processes involved in tumour progression and provides a new tool for therapeutic approaches in MM. PMID- 7873383 TI - Low-dose recombinant interleukin-2 therapy in advanced multiple myeloma. AB - In vitro data have demonstrated autologous T-lymphocytes with anti-tumour activity in multiple myeloma (MM). Therefore a phase I/II trial was conducted to study the feasibility, the effect on several immunological parameters, and the tumour response induction of low-dose recombinant interleukin-2 (rIL-2) in MM patients. 18 MM patients of advanced stages in progress, who had failed on standard chemotherapy received 9 x 10(6) IU/m2 rIL-2 twice daily on days 1 and 2 and 0.9 x 10(6) IU/m2 twice daily for 5 subsequent days per week subcutaneously from days 3 to 56 (repeated every 12 weeks until progression). Patients were treated for between 8 and 1086 + d (mean 241 d) without serious side-effects. 6/17 patients experienced tumour response (2/17 objective tumour mass reduction, 4/17 long-lasting stable disease following tumour progression before initiation of rIL-2 treatment). During therapy the number of eosinophils increased 15-fold, CD4+ T lymphocytes were activated as demonstrated by enhanced CD25 antigen expression, and CD56+ NK cells expanded in the peripheral blood. Furthermore, a diminished pre-treatment ratio of CD4+/CD8+ lymphocytes was normalized during rIL 2 treatment. NK cell activity and lymphokine activated killer (LAK) cell activity was significantly enhanced. Endogenous IL-2 production and elevated soluble IL-2 receptor serum concentrations were induced. Low-dose rIL-2 can stimulate immune enhancement in MM despite the characteristic tumour-induced immunodeficiency. The treatment has proven though limited efficacy in advanced MM. Because most of the responders experienced termination of tumour progression rather than tumour regression, rIL-2 maintenance of chemotherapy-induced remissions should be investigated. PMID- 7873384 TI - Prognostic value of S-phase cells in AML patients. AB - Until now, reports on the cell cycle distribution of AML patients have shown highly variable results which are probably related to the technical heterogeneity of such studies. The aim of the present paper was to analyse in 204 AML patients at diagnosis the proliferative rate (assessed by the number of S-phase cells) of peripheral blood (PB) (126 cases) and bone marrow (BM) (78 cases) cells in order to explore its relationship with disease characteristics. A strong parallelism was observed regarding the relationship between the proliferative rate of the blast cells both in PB and in BM and the disease characteristics. Cases with a high proliferative rate were associated with advanced age, high WBC counts and LDH serum levels, monocytic leukaemias (assessed both by morphological and immunophenotypic criteria) and NK-associated antigens (CD56, CD16). The proliferative activity did not influence the CR rate; in contrast, cases with a high number of S-phase cells had shorter survival. In addition, multivariate analysis showed that age, the expression of CD11b, and the S-phase counts are the only three prognostic factors displaying an independent impact on survival. PMID- 7873385 TI - Detection of BCR-ABL and E2A-PBX1 fusion genes by RT-PCR in acute lymphoblastic leukaemia with failed or normal cytogenetics. AB - To evaluate the use of molecular analysis as a complement to karyotypic analysis in the detection of specific chromosomal abnormalities, the occurrence of t(1;19)(q23;p13) and t(9;22)(q34;q11) was investigated by RT-PCR in 43 diagnostic acute lymphoblastic leukaemia cases in whom cytogenetic investigations had failed (32 cases) or showed only a normal karyotype (> or = 20 normal metaphases, 11 cases). One child (aged 14 years) and five adults (aged 18-60 years) were BCR-ABL positive on first round for M-BCR-ABL (one case) or m-BCR-ABL (one case), or on nested PCR for m-BCR-ABL (three cases). Co-expression of M-BCR-ABL (first-round PCR) and m-BCR-ABL (nested PCR was seen in one case. One m-BCR-ABL-positive case also expressed the E2A-PBX1 fusion transcript. Patients positive for the transcript(s) were older, had higher white blood cell counts and a significantly poorer event-free survival (P < 0.001) than those negative for the transcript. PMID- 7873386 TI - Expression of mdr1, mrp, topoisomerase II alpha/beta, and cyclin A in primary or relapsed states of acute lymphoblastic leukaemias. AB - In a series of 60 ALL samples drawn during different stages of the disease we used a cDNA-PCR approach to analyse the relative mRNA levels of the MDR associated genes encoding mdr1/P-glycoprotein, mrp, and the topoisomerase II isozymes alpha and beta. Expression analysis of the cyclin A gene was included to examine cellular proliferation activity. The expression of gapdh served as an internal standard. Calculating the mean values we found: (i) a distinctly lower mdr1 gene expression in primary ALL and first relapses compared to bone marrow from healthy donors, (ii) no change in mdr1 and mrp, but a decreased topoisomerase II alpha gene expression in first relapses of ALL compared to the primary leukaemia, and (iii) increased mdr1 and mrp levels combined to decreased topoisomerase II alpha levels in recurrent relapses of ALL showing significant correlations (mdr1/mrp: rs = +0.6833, P < 0.05; mdr1/topoII alpha: rs = -0.6727, P < 0.05). The expression of the topoisomerase II alpha gene was correlated to that of cyclin A, indicating a link of its expression to cellular proliferation. Our findings suggest that a multifactorial MDR including mrp appears particularly in recurrent relapses of ALL, which often do not respond to chemotherapy. Nonetheless, some individual samples showed gene expression levels very different from the mean values calculated for a particular state of the leukaemia, indicating the need of an individual expression analysis of MDR-associated genes. PMID- 7873387 TI - Gender and treatment outcome in childhood lymphoblastic leukaemia: report from the MRC UKALL trials. AB - We have examined the factors influencing prognosis in over 4000 children with acute lymphoblastic leukaemia (ALL) aged 1-14 who have been treated on consecutive MRC UKALL trials from 1972 to 1990. During this time the results of treatment have improved steadily but are consistently superior in girls when compared with boys; the 5-year event-free survival in girls improving from 51% to 71% and in boys from 31% to 57%. These results were independent of age and presenting leucocyte count. Boys not only had a testicular relapse rate of 10% but an excess of bone marrow relapse, particularly evident after 2 years from diagnosis. Other prognostic factors included organomegaly and the morphology of leukaemic blast cells; immunophenotype of the leukaemia, however, had no independent significance after allowance for age, sex and leucocyte count. The influence of sex on prognosis was reaffirmed when we examined various methods of identifying children at highest risk of treatment failure for whom alternative therapy such as bone marrow transplantation might be justified. In MRC UKALL X children had been deemed 'high risk' on the basis of leucocyte count alone, but with further follow-up it has become apparent that girls with an initial leucocyte count of > 100 x 10(9)/l have a similar prognosis to boys with a lower count. We therefore derived a risk score based on sex, age and count which has given better discrimination between standard risk (66% 5-year survival) and poor risk (39%) survival than other methods. This group of worse-risk children includes 16% of boys but only 3% of all girls. Gender remains an important prognostic factor in UKALL trials and there are very few girls who are at highest risk of treatment failure. The reasons for this remain unclear, but the pattern of relapses suggests that boys more often get inadequate systemic therapy. We postulate that the reasons for treatment failure may relate to sensitivity to continuing (maintenance) chemotherapy. PMID- 7873388 TI - The two CD23 isoforms display differential regulation in chronic lymphocytic leukaemia. AB - B lymphocytes from chronic lymphocytic leukaemia (B-CLL) patients express the two CD23 isoforms (type A and B), which differ only in their intracytoplasmic domain. The abnormal regulation of the CD23 antigen in response to IL-4, IFNs alpha and gamma results in CD23 over-expression on B-CLL cells. Our present study shows that the two CD23 isoforms are differentially and abnormally regulated on B-CLL cells. IL-4 selectively up-regulates CD23 type A mRNA in five different B-CLL patients, whereas in normal B cells it enhances CD23 type A and is the most potent inducer of type B. In contrast, phorbol esters (PMA) up-regulate both CD23 isoforms in the malignant B cells and specifically increases type B in normal B cells. We next postulated that cytokines other than IL-4 regulate CD23 B isoform in B-CLL cells and therefore examined the effect of IL-2, IFN-gamma and IFN alpha. We found that the ability of a given cytokine to induce B-CLL growth (i.e. IL-2 and IFN alpha) is concurrent with a selective up-regulation of CD23 type B mRNA, whereas lymphokines that have no B cell growth activity (i.e. IL-4 and IFN gamma) specifically increase CD23 type A mRNA. We next showed that IL-4 and IFN gamma prevent hydrocortisone-induced programmed cell death and that the rescued malignant B cells mainly express CD23 type A. Given that CD23 molecule has been reported to play a role in normal B cell proliferation and survival, it is therefore proposed that in B-CLL cells the expression of CD23 type A may be related to cell viability and that of type B to cell proliferation. These data suggest that the CD23 molecule may contribute to the physiopathology of the disease which is characterized by the accumulation of long-lived and slow dividing monoclonal B cells. PMID- 7873389 TI - A flow cytometric assay using mepacrine for study of uptake and release of platelet dense granule contents. AB - Diagnosis of platelet dense granule storage pool disease and release defects at present requires a combination of studies including lumiaggregometry, conventional platelet aggregation, radioactive serotonin uptake and release, and electron microscopy. Flow cytometric methods have been developed to study platelet activation, aggregation, and alpha-granule protein release. Here, we have investigated the use of flow cytometry for analysis of platelet dense granule content uptake and release using mepacrine as a fluorescent marker. Mepacrine (quinacrine) is rapidly taken up and localized in dense granules of platelets. For the assay, as little as 20 microliters of blood from a fingerstick collected without anticoagulant or venous blood collected in 3.8% sodium citrate were diluted 1:40 with 2 ml Hanks balanced salt solution (BSS). 300 microliters of this cell suspension were incubated with mepacrine alone, or simultaneously with a mouse monoclonal antibody to human platelet glycoprotein IIb (Tab), used as a platelet-specific marker. The bound monoclonal antibody was then indirectly labelled with the fluorochrome, RED670. 100 microliters of the sample were further diluted with Hanks BSS for one- or two-colour flow cytometric analysis. To verify that mepacrine uptake was related to platelet dense granule content, platelets of beige mice, a strain with dense granule deficiency, were examined. Their mepacrine uptake was substantially decreased compared to that of normal mice. Decreased mepacrine uptake also was demonstrated in platelets of a patient with Hermansky-Pudlak syndrome in which a deficiency of platelet dense granules is characteristic. In both human and mouse platelets, mepacrine uptake was proportional to platelet size. Thrombin induced mepacrine release in a dose dependent manner from 0.003 to 0.4 U/ml. Therefore both platelet uptake and release of mepacrine can be readily detected by flow cytometry. Flow cytometry provides an attractive alternative to aggregation and radioactive serotonin as methods to study defects in platelet dense granule function. PMID- 7873390 TI - A three-base deletion removing a leucine residue in a leucine-rich repeat of platelet glycoprotein Ib alpha associated with a variant of Bernard-Soulier syndrome (Nancy I). AB - Leucine-rich repeats are conserved structural motifs present in the four components of the human platelet glycoprotein Ib/IX/V complex receptor for the adhesive protein von Willebrand factor. The absence or abnormality of this complex is responsible for Bernard-Soulier disease, an autosomal recessive bleeding disorder. We report a deletion of leucine 179, located in a highly conserved position of the seventh leucine-rich repeat of GPIb alpha, found in a variant form of Bernard-Soulier disease (Bernard-Soulier Nancy I). Three affected siblings of a family were characterized by absence of ristocetin-induced platelet agglutination, although ADP aggregation was normal. Flow cytometry studies showed detectable amounts of all four members of the GPIb/IX/V complex on the surface of the patients' platelets. Western blotting revealed normal levels of GPIX, decreased levels of GPIb beta and GPV, and < 1% of GPIb alpha. RT-PCR studies showed the presence of mRNA coding for GPIb alpha, GPIb beta, GPIX and GPV. Sequencing showed a three-base deletion which results in the absence of a leucine residue, highly conserved across the seven leucine-rich repeats of GPIb alpha and also within the other members of the leucine-rich glycoprotein family. The absence of the leucine 179 in a patient's GPIb alpha is believed to cause a conformational change in the protein which would account for the lack of binding of most of the MoAbs tested and would be responsible for the absence of von Willebrand factor binding. These results point to the leucine-rich region of GPIb alpha as being required for the correct exposure of the von Willebrand binding site as well as for the correct assembly and stability of the GPIb/IX/V complex on the platelet surface. PMID- 7873391 TI - Anti beta 2 glycoprotein I antibodies: detection and association with thrombosis. AB - It has been demonstrated that antiphospholipid antibodies (aPL) recognize epitopes formed by anionic phospholipids and protein cofactors. beta 2 glycoprotein I (beta 2GPI) is accepted as the cofactor of anticardiolipin antibodies (aCL). In the present study we explored the presence and clinical associations of anti beta 2GPI antibodies of IgG isotype (a beta 2GPI-IgG), measured by ELISA. We studied sera from 169 patients with aCL and/or lupus anticoagulant (LA), including 52 patients with systemic lupus erythematosus and 49 with primary antiphospholipid syndrome (PAPS). We found 31.9% positive sera for a beta 2GPI-IgG in the whole population and 48.6% in the aCL-IgG(+) group. There was a good correlation between the titre of aCL-IgG and the optical density for a beta 2GPI-IgG (r = 0.69, P < 0.01). The presence of a beta 2GPI-IgG was associated with the presence of aCL-IgG (P < 0.0001) and LA (P < 0.0005). However, none of 23 LA (+) patients without aCL had a beta 2GPI-IgG. We found a statistically significant association between the presence of a beta 2GPI-IgG and a history of venous thromboembolism (VTE) in our patients (P < 0.005). This association was observed in PAPS (P < 0.05) but not in secondary antiphospholipid syndrome (SAPS). Our study confirms that some aPL(+) sera react with beta 2GPI in special experimental conditions. In addition, the presence of these antibodies is associated with a history of VTE. PMID- 7873392 TI - Pharmacokinetics of the oral iron chelator deferiprone (L1) in patients with iron overload. AB - Single oral dose pharmacokinetics of the iron chelator deferiprone (L1) were studied in 24 patients with chronic iron overload and correlated with 24 h urinary iron excretion (UIE) and creatinine clearance. Absorption of L1 was rapid with a t1/2 of 22.2 +/- 17.7 (mean +/- SD) min. The elimination half-life (elt1/2) of the drug was 91.1 +/- 33.1 min and of its metabolite, L1-glucuronide (L1G) 147.7 +/- 52.0 min. Creatinine clearance of the patients correlated significantly with the elimination t1/2 of L1G (r = -0.79, P = 0.002). There was also a significant correlation between 24 h UIE in the 14 patients studied and L1 versus time area under the curve (AUC) (P = 0.007). The total amount of L1 recovered in urine in 24 h comprised 77.9 +/- 13.3% of the L1 dose. L1 efficiency (the 24 h UIE divided by the amount of iron the oral dose of L1 is capable of binding) in the 14 patients was 3.8 +/- 1.9%. These data show for the first time that the urinary elimination of L1G is influenced by the renal function of the patient. Although no significant accumulation of L1 and L1G will occur in most of the patients if L1 is given more than once daily, in some patients with impaired renal function, L1G may accumulate. PMID- 7873393 TI - Heteroduplex screening for molecular defects in factor IX genes from haemophilia B families. AB - Heteroduplex screening of amplified fragments containing sequences of all known small haemophilic mutations in the factor IX gene localized mutations in 18 new families: 12 were at common recurrent sites; three were novel. Carriers and/or patients from each of 41 families with mutations in 7 exons and 5' and 3' non coding regions were positive. PMID- 7873394 TI - IL-3 increases marrow and peripheral erythroid precursors in chronic pure red cell aplasia presenting in childhood. AB - In most patients with Diamond-Blackfan anaemia (DBA) the addition of IL-3 to in vitro cultures increases the number of erythroid progenitors. However, a small proportion of patients show an erythroid response to in vivo administration of IL 3. We treated two adult patients with corticosteroid-refractory DBA, who had shown a clear in vitro erythroid response to IL-3, with increasing doses of IL-3 (from 2.5 to 10 micrograms/kg/d) by subcutaneous injections for 7 and 9 weeks. Monitoring of marrow and circulating progenitors showed a sustained elevation of BFU-E and CFU-E as well as an increase of other progenitors and CD34+ cells during therapy. However, this effect did not translate into a clear clinical response, although transfusion requirements decreased transiently in one patient. This report shows that a sustained elevation of erythroid progenitors induced by in vivo IL-3 administration may not translate into an increase of mature red cells production in DBA patients. PMID- 7873395 TI - Rapid and sensitive non-radioactive assay for the detection of clonal gene rearrangements in B-lineage acute leukaemia. AB - We have applied a simple and non-radioactive assay system used in conjunction with polymerase chain reaction amplification and high-resolution polyacrylamide gel electrophoresis to detect clonal immunoglobulin gene rearrangements in leukaemia patient DNA. This technique is as sensitive as isotopic methods, allowing the detection of clonal DNA diluted 1 in 10,000 in non-clonal DNA. PMID- 7873396 TI - Haptoglobin therapy for acute favism: a Japanese boy with glucose-6-phosphate dehydrogenase Guadalajara. AB - We report the case of a 2-year-old Japanese boy with acute favism who was treated with human haptoglobin products. He had been exhibiting chronic nonspherocytic haemolytic anaemia until the diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency when 14 months old. He suffered a favic crisis at 24 months of age, when the administration of haptoglobin was effective for relieving bilirubinaemia and haemoglobinuria. Serum-free Hb rapidly decreased to normal levels despite the sustained level of serum lactate dehydrogenase. His G6PD gene was G6PD Guadalajara. This is the first application of haptoglobin therapy for acute favism and the first reported case of Japanese G6PD deficiency with typical favic crisis. Haptoglobin treatment might be helpful for managing the haemolytic crisis in the disease. PMID- 7873397 TI - Lack of G blood group antigen in DIIIb erythrocytes is associated with segmental DNA exchange between RH genes. AB - The Rh blood group antigens D, Cc and Ee are encoded by two highly related genes, RHD and RHCE. Almost all red cells which carry D and all cells which carry C also express the G (Rh12) antigen. In this report we have determined the molecular basis of the DIIIb category phenotype which represents a very rare condition characterized by the presence of most of the D epitopes and the total absence of the antigen G. mRNA sequencing and Southern blot analysis of two unrelated samples indicated that the DIIIb category phenotype is associated with a segmental DNA exchange between exon 2 of the RHD and RHCE genes resulting in three D-->c amino acid substitutions (Ile60Leu, Ser68Asn and Ser103Pro). PMID- 7873398 TI - The evaluation of results of CMV antigenaemia assays in bone marrow transplant recipients. PMID- 7873399 TI - Anti-HPA-1b really causes neonatal thrombocytopenia. PMID- 7873400 TI - Atypical chronic myeloid leukaemia and chronic myelomonocytic leukaemia in children. PMID- 7873401 TI - Localization of thoracic imaginal-disc precursor cells in the early embryo of Drosophila melanogaster. AB - Our previous cell lineage analysis of the thoracic disc primordia of Drosophila showed that at the blastoderm and early gastrula stage, cells are not yet committed to form either larval or imaginal tissue (Meise and Janning, 1993). We have now refined our studies on the cell lineage and have mapped the imaginal primordia in the thoracic region. Homotopic transplantations of single cells within the thoracic region of blastoderm and early gastrula stages show that the precursor cells of thoracic imaginal discs are locally restricted to a small lateral area of the thoracic region. Clones labelling leg discs frequently included the Keilin's organs. Heterotopic transplantations along the dorsoventral axis indicate that cells within the thoracic region are not yet committed with respect to larval or imaginal tissue, their fate being dependent on the position where the transplanted cell had been deposited. On the other hand, cells taken from the abdominal anlagen and transplanted into the region of thoracic disc primordia could not participate in the formation of imaginal discs. This shows that, in contrast to the dorsoventral axis, determinative events had separated primordia along the anterior-posterior axis. PMID- 7873402 TI - Multiple regulatory elements direct the complex expression pattern of the Drosophila segmentation gene paired. AB - The paired (prd) gene of Drosophila belongs to the pair-rule class of segmentation genes involved in establishing the metameric organization of the Drosophila body plan. The complex expression pattern of prd has previously been shown to depend upon a number of segmentation genes, including gap and pair-rule genes. In an attempt to characterize and analyze the regulatory regions necessary and sufficient for prd expression, we have identified an 18-kb genomic fragment, consisting of the transcribed portion of prd and 10 kb of 5'- and 5 kb of 3' flanking region, that is able to rescue prd mutant embryos to full viability. Analysis of a series of prd-lacZ fusion constructs containing progressively reduced lengths of prd 5'-flanking sequences delimits different cis-regulatory regions. The entire 5'-flanking region directs fusion gene expression in a pattern similar, but not identical, to the endogenous prd protein pattern. This 10-kb fragment contains both activator and repressor regions that mediate the establishment of the seven-stripe prd pattern, as well as the splitting into anterior and posterior stripes for the 14-stripe expression phase. The prd intron in combination with a minimal upstream region (0.15 kb) is able to direct low levels of prd-lacZ fusion gene expression in stripes. Information for expression of the anterior dorsal spot and of the early seven-stripe pattern is located downstream of the prd coding region. We propose that regulation of prd by pair rule and gap gene products is mediated by upstream and downstream cis-regulatory elements. Regulation during separate but overlapping phases of expression by separable regulatory regions might be a general characteristic of segmentation genes. PMID- 7873403 TI - Fgf-8 expression in the post-gastrulation mouse suggests roles in the development of the face, limbs and central nervous system. AB - Fgf-8 is a member of the fibroblast growth factor (FGF) family that was initially identified as an androgen-inducible growth factor in a mammary carcinoma cell line. Alternative splicing of the primary Fgf-8 transcript results in three messenger RNAs which code for secreted FGF-8 protein isoforms that differ only in their mature amino termini. Fgf-8 RNA is present from day 10 through 12 of murine gestation when analyzed by northern blot analysis, suggesting that Fgf-8 normally functions during post-gastrulation development. To characterize the temporal, spatial and isoform-specific aspects of Fgf-8 expression during mouse development, we performed in situ hybridization and ribonuclease protection assays between the days 8 and 16 of gestation. Fgf-8 expression is first detected at day 9 of gestation in the surface ectoderm of the first branchial arches, the frontonasal process, the forebrain and the midbrain-hindbrain junction. At days 10-12 of gestation, Fgf-8 expression is detected in the surface ectoderm of the forelimb and hindlimb buds, in the nasal pits and nasopharynx, in the infundibulum and in the telencephalon, diencephalon and metencephalon. Fgf-8 expression continues in the developing hindlimbs through day 13 of gestation but is undetectable thereafter. Ribonuclease protection assays reveal that RNAs coding for all three FGF-8 isoforms are present at days 10-12 of gestation. These results reveal a unique temporal and spatial pattern of Fgf-8 expression in the developing mouse and suggest a role for this FGF in multiple regions of ectodermal differentiation in the post-gastrulation mouse embryo. PMID- 7873404 TI - Characterization of the mouse HNF-4 gene and its expression during mouse embryogenesis. AB - Hepatocyte nuclear factor 4 (HNF-4) is a member of the nuclear receptor gene superfamily with unknown ligand. It has been assumed to play an important role in the regulation of gene expression in the liver. Here, we report the cloning and characterization of the mouse HNF-4 gene, as well as its expression during embryogenesis. The HNF-4 protein is encoded by ten exons. The gene structure is unique in the steroid receptor superfamily in that the second zinc finger is encoded by two exons. HNF-4 mRNA is expressed in a limited number of mouse adult tissues: liver, kidney, intestine, stomach and skin. HNF-4 could play an important role in the formation and function of visceral yolk sac and in the development of the liver and kidney since its mRNA, as determined by in situ hybridization, appears upon primary differentiation of these organs. As a first step in the study of the regulatory elements of the HNF-4 gene, we mapped the transcription start site and carried out DNase I hypersensitive site (HS) analysis over a region of approximately 22kb upstream of the gene. The complexity of the HSs suggests that multiple elements might contribute to the transcriptional regulation of the HNF-4 gene. PMID- 7873405 TI - Genetic analysis of the Drosophila single-minded gene reveals a central nervous system influence on muscle development. AB - The Drosophila single-minded gene is expressed in the embryonic central nervous system midline cells and plays a critical role in central nervous system development. Additional expression of single-minded is found in a subset of ventral muscle precursor cells. Null mutations of single-minded result in an alteration of the ventral oblique muscles, such that muscle fibers form inside the embryo above the central nervous system. This defect is due to the mislocalization of a subset of mesodermal precursor cells. The muscle defect observed in single-minded null mutations is not due to the absence of single minded expression in muscle precursor cells and likely results from an influence of the central nervous system on ventral muscle development. PMID- 7873407 TI - Regulation of calcium slow channels of heart by cyclic nucleotides and effects of ischemia. AB - The slow Ca2+ channels (L-type) of the heart are stimulated by cAMP. Elevation of cAMP produces a very rapid increase in the number of slow channels available for voltage activation during excitation. The probability of a Ca2+ channel opening and the mean open time of the channel are increased. Therefore, any agent that increases the cAMP level of the myocardial cell will tend to potentiate ICa, Ca2+ influx, and contraction. The action of cAMP is mediated by PK-A and phosphorylation of the slow Ca2+ channel protein or an associated regulatory protein (stimulatory type). The myocardial slow Ca2+ channels are also regulated by cGMP, in a manner that is opposite or antagonistic of that of cAMP. This has been demonstrated at both the macroscopic level (whole-cell voltage clamp) and the single-channel level. The effect of cGMP is mediated by PK-G and phosphorylation of a protein, for example, a regulatory protein (inhibitory type) associated with the Ca2+ channel. It has been demonstrated that introduction of PK-G intracellularly causes a relatively rapid inhibition of ICa(L) in both chick and rat heart cells. In addition, cGMP/PK-G act to stimulate a phosphatase that dephosphorylates the Ca2+ channel. In addition to the slower, indirect pathway- exerted via cAMP/PK-A--there is a faster, more direct pathway for ICa(L) stimulation by the beta-adrenergic receptor. The latter pathway involves direct modulation of the channel activity by the alpha subunit (alpha S*) of the GS protein. PK-C and calmodulin-PK also may play roles in the regulation of the myocardial slow Ca2+ channels, possibly mediated by phosphorylation of some regulatory type of protein. Both protein kinases stimulate the activity of the slow Ca2+ channels. Thus, it appears that the slow Ca2+ channel is a complex structure, including perhaps several associated regulatory proteins, which can be regulated by a number of factors intrinsic and extrinsic to the cell (Fig. 9). The cyclic nucleotides also have effects on the slow Ca2+ channels in cells other than cardiac muscle, including neurons, smooth muscle, and skeletal muscle fibers (Tables III and IV). In cardiac muscle, the two cyclic nucleotides have opposing effects, cAMP stimulating and cGMP inhibiting. In some smooth muscles (e.g., vascular), both cyclic nucleotides act in the same direction, namely, both inhibit ICa(L). In skeletal muscle, both cAMP and cGMP act in the same direction on ICa(L), but to stimulate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7873406 TI - Cloning and analysis of a new developmentally regulated member of the basic helix loop-helix family. AB - We have isolated a basic helix-loop-helix (bHLH) family member from an embryonic chick-brain cDNA library. This 3.86-Kb cDNA, GbHLH1.4, exhibits extensive sequence similarity in the bHLH domain with Drosophila daughterless and the vertebrate cDNAs E12 and HTF4. Outside of the bHLH region the similarity is significantly reduced. GbHLH1.4 recognizes a 4.0-Kb mRNA and in situ hybridization analysis shows that GbHLH1.4 mRNA is widely expressed at early stages of development but becomes progressively restricted as embryogenesis proceeds. At later stages of embryonic development, mRNA transcripts are localized to several structures including the ventricular layers of the spinal cord and brain, the facial primordia, dorsal root ganglia and heart muscle and cardiac valves. Strikingly, GbHLH1.4 expression in chick embryos exhibits significant overlap with that reported for the murine negative HLH regulator, Id. PMID- 7873408 TI - Effects hypoxia/reoxygenation on intracellular calcium ion homeostasis in ventricular myocytes during halothane exposure. PMID- 7873409 TI - Anesthetic actions on calcium uptake and calcium-dependent adenosine triphosphatase activity of cardiac sarcoplasmic reticulum. PMID- 7873410 TI - Interaction of anesthetics and catecholamines on conduction in the canine His Purkinje system. AB - The findings in papillary muscles that epinephrine facilitates conduction at Purkinje fiber-muscle junctions and in the endocardium are consistent with older observations that activation of myocardial beta-adrenergic receptors speeds conduction and activation in the heart and thereby increases the synergy of contraction (46,47). The cellular mechanism underlying this action is probably increased cell-to-cell coupling between muscle fibers secondary to elevation of cyclic AMP (19,48). However, the findings that epinephrine alone or with halothane transiently slows conduction in the Purkinje layer while simultaneously improving conduction across Purkinje-muscle junctions and in the endocardium may represent proarrhythmic actions. These actions could facilitate arrhythmogenesis by transiently increasing regional differences of activation and repolarization times in the conduction system and myocardium and thereby increasing vulnerability to induction of reentry by premature impulses. Such a proarrhythmic effect could explain an older observation that low-dose norepinephrine infusions decrease the threshold for induction of fibrillation by two premature beats in pentobarbital-anesthetized animals (49). The cellular basis underlying the different responses of Purkinje fibers and the endocardial muscle layer to catecholamines, in which velocity decreased and increased, respectively, is not known. Our working hypothesis to explain this action in canine Purkinje fibers is a mechanism involving activation of WB4101-sensitive alpha 1-adrenoceptor, G protein coupling to phospholipase C and the generation of DAG and IP3 leading to modulation of cell-to-cell coupling, which is potentiated in the presence of partial uncoupling by halothane. The different responses of Purkinje and myocardial fibers are speculated to result from differences in the relative density of this subtype of alpha 1-adrenoceptor, differences in the subcellular effector coupling mechanisms, or differences in the specific connexin proteins forming gap junctions between Purkinje and myocardial fibers (50). PMID- 7873411 TI - Anesthetics, catecholamines, and ouabain on automaticity of primary and secondary pacemakers. PMID- 7873413 TI - Effects of inhibition of transsarcolemmal calcium influx on content and releasability of calcium stored in sarcoplasmic reticulum of intact myocardium. PMID- 7873412 TI - The role of L-type voltage-dependent calcium channels in anesthetic depression of contractility. PMID- 7873414 TI - Arrhythmogenic effect of inhalation anesthetics: biochemical heterogeneity between conduction and contractile systems and protein unfolding. PMID- 7873415 TI - Potassium channel current and coronary vasodilatation by volatile anesthetics. PMID- 7873416 TI - Functional adaptation to myocardial ischemia: interaction with volatile anesthetics in chronically instrumented dogs. PMID- 7873417 TI - Potassium channel opening and coronary vasodilation by halothane. PMID- 7873418 TI - Volatile anesthetics and coronary collateral circulation. PMID- 7873419 TI - Myocardial oxygen supply-demand relations during isovolemic hemodilution. AB - The findings presented in this article pertain strictly to the specific conditions of the studies and should be extrapolated to human patients with caution for several reasons. First, the experimental model of a single acute coronary stenosis is a rare clinical occurrence, and it ignores the influence of the well-developed collateral circulation and impaired endothelial function which may accompany long-standing coronary artery disease (22). Second, the absolute hematocrit at which cardiac dysfunction arises would likely vary if a different anesthetic technique or diluent were used, or if the study were carried out in the absence of thoracotomy and positive-pressure ventilation or at a reduced body temperature. Nevertheless, the present findings provide broad guidelines for assessing when hemodilution may be used safely as a method of blood conservation. They suggest (1) that relatively severe hemodilution alone or moderate hemodilution combined with controlled hypotension with either SNP or ADEN may be used safely if cardiac function is normal and the coronary circulation is not obstructed, but (2) that even moderate hemodilution alone may be unsafe in patients in whom the coronary vasodilator reserve is exhausted or severely depleted by a proximal stenosis. PMID- 7873420 TI - Plasma membrane Ca(2+)-ATPase as a target for volatile anesthetics. PMID- 7873421 TI - Enhancement of halothane action at the ryanodine receptor by unsaturated fatty acids. PMID- 7873422 TI - Volatile anesthetic effects on inositol trisphosphate-gated intracellular calcium stores in GH3 cells. AB - The experimental results reviewed in this article indicate that clinically relevant concentrations of halothane (and isoflurane and octanol) cause calcium to leak from IP3-gated intracellular calcium stores, resulting in depletion of the stores. Depletion of intracellular Ca2+ stores should attenuate the actions of a variety of hormones and neurotransmitters that use the IP3 pathway to produce their effects, potentially contributing to many volatile anesthetic side effects including bronchodilatation, vasodilatation, and unresponsiveness to vasoconstrictive agents. PMID- 7873423 TI - Differential control of blood pressure by two subtypes of carotid baroreceptors. PMID- 7873424 TI - Sympathetic activation with desflurane in humans. AB - Although the blood pressure lowering effects of desflurane and isoflurane were similar at equi-MAC, we noted a different pattern of response during intervals of rapidly increasing the inspired concentration of desflurane, when substantial increases in SNA, HR, and MAP occurred. Because of the lower potency of desflurane compared to isoflurane, higher concentrations of desflurane are necessary to establish an adequate surgical plane of anesthesia. Although clinically relevant concentrations of isoflurane did not trigger sympathetic activation, isoflurane triggered responses at an inspired concentration (approximately 5%) nearly equal to that of desflurane. The present research demonstrates that the initial exposure to desflurane in clinically relevant concentrations following anesthetic induction and the deepening of anesthesia with higher concentrations of desflurane can be profoundly sympatho-excitatory. Considerable caution should be taken when administering desflurane to patients who may be placed at risk by these responses. PMID- 7873425 TI - Randomized, prospective comparison of halothane, isoflurane, and enflurane on baroreflex control of heart rate in humans. PMID- 7873426 TI - Baroreflex modulation by isoflurane anesthesia in normotensive and chronically hypertensive rabbits. PMID- 7873427 TI - Excitation-contraction uncoupling and vasodilators for long-term cold preservation of isolated hearts. PMID- 7873428 TI - Effects of isoflurane on regulation of capacitance vessels under normotensive and chronically hypertensive conditions. PMID- 7873429 TI - Effect of volatile anesthetics on baroreflex control of mesenteric venous capacitance. PMID- 7873430 TI - Effect of general anesthesia on modulation of sympathetic nervous system function. PMID- 7873431 TI - Inhibition of nitric oxide-dependent vasodilation by halogenated anesthetics. PMID- 7873432 TI - Effects of epidural anesthesia on splanchnic capacitance. AB - Splanchnic veins play an important role in the active control of total body circulatory capacitance. The effects of epidural anesthesia on splanchnic venous capacitance have not previously been examined. A rabbit model using direct measures of mesenteric vein diameter and sympathetic efferent nerve activity was used to test the response to epidural lidocaine at three different doses and to intramuscular lidocaine at two doses. Epidural anesthesia produced hypotension, mesenteric venodilatation, and interruption of sympathetic activity. Maximal changes of these parameters were comparable in the three epidural dosage groups but were more prolonged with increasing dose. High-dose systemic lidocaine caused smaller changes in arterial pressure and sympathetic activity. Further experiments were done to investigate the mechanism of splanchnic venodilatation. Passive vein distension and effects of circulating lidocaine or catecholamines are not likely contributing factors. Blocks limited to thoracic segments, but including the origin of splanchnic preganglionic fibers, produce comparable mesenteric venodilatation and sympathetic interruption as extensive thoracolumbar blocks. Blocks limited to lumbar segments, however, showed mesenteric venoconstriction and increased splanchnic sympathetic activity. The variable responses in splanchnic capacitance with the onset of epidural anesthesia are the result of the competing influences of increased sympathetic activity from decreasing blood pressure and blockade of sympathetic fibers to the splanchnic veins. PMID- 7873433 TI - Anesthetic modulation of pulmonary vascular regulation. AB - These results provide compelling evidence that general anesthesia can alter neural, hymoral, and local mechanisms of pulmonary vascular regulation. A clear strength of these studies is that we have assessed these various mechanisms of pulmonary vascular regulation in the conscious state, and then again in the same animal during general anesthesia. Our studies in chronically instrumented conscious dogs have documented that regulation of the pulmonary vascular P/Q relationship is multifactorial, and that these vascular mechanisms are interactive. These results in conscious animals serve as a database to assess the specific effects of general anesthesia on pulmonary vascular regulation. A striking finding in these studies is that different anesthetics can have differential effects on neural, humoral, and local mechanisms of pulmonary vascular regulation. Without this fundamental information, it is difficult to interpret previous experimental studies that have utilized background anesthetics. Moreover, this information is essential for the adequate clinical management of patients in the perioperative period. These in vivo studies have allowed us to identify the overall effects of general anesthetics on the integrative response of the intact organism to these diverse pulmonary vasoregulatory pathways. Our next objective is to elucidate the cellular mechanisms that mediate the effects of general anesthetics on these various mechanisms of pulmonary vasoregulation. To that end, we are now performing in vivo studies utilizing isolated pulmonary arterial rings to elucidate abnormalities in the various signal transduction pathways that could be responsible for the effects of general anesthetics. We propose to identify the loci of dysfunction in the signal transduction pathways that mediate the pulmonary vascular effects of general anesthetics on cAMP-, cGMP-, and K+ATP channel-mediated pulmonary vasodilation, as well as alpha 1- and angiotensin mediated pulmonary vasoconstriction. These combined in vivo and in vitro approaches are complementary and can be used to delineate the effects and mechanisms of action of general anesthetics on pulmonary vasoregulation. PMID- 7873434 TI - Pulmonary mechanics changes associated with cardiac surgery. PMID- 7873435 TI - Inhaled nitric oxide in adult respiratory distress syndrome and other lung diseases. PMID- 7873436 TI - First pass uptake in the human lung of drugs used during anesthesia. PMID- 7873437 TI - Lactic acidosis and pH on the cardiovascular system. PMID- 7873438 TI - Role of oxygen free radicals and lipid peroxidation in cerebral reperfusion injury. PMID- 7873439 TI - Effects of volatile anesthetics on cerebrocortical laser Doppler flow: hyperemia, autoregulation, carbon dioxide response, flow oscillations, and role of nitric oxide. PMID- 7873440 TI - Cerebral blood flow during isovolemic hemodilution: mechanistic observations. PMID- 7873441 TI - Cerebral physiology during cardiopulmonary bypass: pulsatile versus nonpulsatile flow. AB - In summary, neurological injury continues to be a significant source of perioperative morbidity and mortality in cardiac surgical procedures. To reduce the incidence and/or severity of these complications, a better understanding of the cerebral physiology of CPB is needed. Specifically, it is important to determine how the conduct of CPB either contributes to or modifies the response of the brain to neurological insults. Our research indicates that, in the uninjured brain, nonpulsatile perfusion per se does not appear disadvantageous in terms of brain blood flow or oxygen metabolism at 27 degrees C. Conversely, pulsatile perfusion does not appear to confer any special benefits. Whether pulsatility might influence neurological outcome in the presence of an ischemic insult remains to be determined. PMID- 7873442 TI - Anesthetic actions on cardiovascular control mechanisms in the central nervous system. PMID- 7873443 TI - Troponin T as a marker of perioperative myocardial cell damage. AB - Unstable angina in patients undergoing CABG surgery is associated with a higher morbidity and mortality compared to patients with stable angina. Mortality ranges between 2 and 10% (20, 21). The importance of the preoperative status is only clear and well documented for patients with unstable angina who are unresponsive to medical treatment, patients who undergo emergency revascularization, and for patients with failed angioplasty. The adverse outcome in elective patients with unstable angina was statistically not significantly different from those with stable angina. Therefore, we may assume that in stabilized patients with unstable angina and minor myocardial cell damage intraoperative determinants like the duration of the aortic clamping period or the degree of revascularization are more relevant than the preoperative ones. These determinants may also be reflected by a marked and significant increase of troponin T in both groups during and after surgery. As for other cardiac enzymes, this increase of troponin T beginning immediately after reperfusion of the cardioplegic heart may limit its diagnostic value after cardiac surgery (6,22). On the other hand, troponin T may serve as a marker in assessing the effectiveness of different cardioprotective measures. Nevertheless, preoperatively elevated troponin T levels may indicate a jeopardized myocardium with an ongoing process of myocardial cell damage and may be of prognostic value. Antianginal and antiischemic therapy, therefore, has to be continued and completed until the day of surgery in these high-risk patients. PMID- 7873444 TI - Silent myocardial ischemia: pathophysiology and perioperative management. AB - Silent ischemia has been called the silent killer. Pain does not kill patients with coronary heart disease--ischemia does, whether it happens to be painful or silent. An increased awareness of this still puzzling phenomenon may be of great importance in the pre- and perioperative management of patients with coronary heart disease, and improved detection and management of silent ischemia are likely to reduce the risk of perioperative cardiac events. PMID- 7873445 TI - Effect of halothane on sarcolemmal calcium channels during myocardial ischemia and reperfusion. AB - The present results provide indirect support for other studies which showed that halothane inhibited the Ca2+ accumulation associated with myocardial ischemia in isolated guinea pig hearts (6), demonstrating a potentially beneficial effect of the anesthetic on the ischemic heart. The role of halothane in preventing ischemia-induced dysrhythmias and attenuation of free radical generation on reperfusion offers a new potential use during open heart surgery. The method of continuous perfusion of oxygenated blood cardioplegia, retrogradely, through the coronary sinus, enables a concomitant administration of the VA before and during the ischemic period of the cardiopulmonary bypass. Further studies may promote the use of the volatile anesthetic when myocardial ischemia and reperfusion are present during open heart surgery. PMID- 7873446 TI - Myocardial ischemic preconditioning. PMID- 7873447 TI - Emerging diversities in the mechanism of action of steroid hormones. AB - The classical genomic action of steroid hormones acting through intracellular receptors is well recognized. Within this concept of action, questions regarding the ultimate fate of the hormone and lack of a tight correlation between tissue uptake and biological activity with receptor binding remain unanswered. Evidence has accumulated that steroid hormones can exert non-classical action that is characterized by rapid effect of short duration. In most of these cases, the hormone effects occurs at the membrane level and is not associated with entry into the cell. The possible mechanisms for these non-classical actions are: (a) changes in membrane fluidity; (b) steroid hormone acting on receptors on plasma membranes; (c) steroid hormones regulating GABAA receptors on plasma membranes; and (d) activation of steroid receptors by factors such as EGF, IGF-1 and dopamine. Data have also been obtained indicating that receptor-mediated insertion of steroid hormones into DNA may take place with the steroid acting as a transcription factor. These new proposed mechanism of action of steroid hormones should not be viewed as a challenge to the classical mechanism. These diverse modes of action provide for an integrated action of hormones which may be rapid and of short duration or prolonged to address the physiological needs of the individual. PMID- 7873448 TI - Hormone-induced hyperphosphorylation of specific phosphorylated sites in the mouse glucocorticoid receptor. AB - The glucocorticoid receptor (GR) is phosphorylated in its basal state, and rapidly undergoes hormone-induced hyperphosphorylation after binding glucocorticoids. Previously, we have identified seven phosphorylated sites in the mouse GR. Most of the sites are located in the regions of the N-terminal domain that are necessary for maximum transcriptional activity and reduce nonspecific binding to DNA. Using WCL2 cells, which overexpress mouse GRs, we now quantitate hormone-induced hyperphosphorylation at each of these sites. Addition of triamcinolone acetonide to WCL2 cells results in significant hyperphosphorylation at the majority of the sites. The hyperphosphorylation ratio, i.e. the 32P incorporation into GRs from hormone-treated cells divided by 32P incorporation into GRs from untreated cells, was above 1.0 for all sites but serine 150 and threonine 159. Serine 220 displays marked hormone dependence, with a ratio of 3. For most sites the ratio was about 1.5. Hormone-induced hyperphosphorylation not only increases the charge at selected phosphorylated sites but also provides a substantial increase in the overall negative charge around the region of the N terminal domain that is involved in transactivation. PMID- 7873449 TI - Cloning, sequencing and tissue-distribution of mouse 11 beta-hydroxysteroid dehydrogenase-1 cDNA. AB - 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) reversibly converts physiological glucocorticoids (cortisol, corticosterone) to inactive 11-dehydro forms, and thus controls glucocorticoid access to receptors in a variety of tissues. We have cloned a cDNA encoding 'liver-type' 11 beta-HSD (11 beta-HSD1) from the mouse using PCR, and have determined its nucleotide sequence. Mouse 11 beta-HSD1 cDNA showed 91% identity to rat 11 beta-HSD1 cDNA. There was 87% amino acid identity with rat 11 beta-HSD1 with conservation of the putative cofactor and substrate binding domains. Northern blot analysis of mouse tissues demonstrated abundant 11 beta-HSD1 message in the liver, kidney and lung, with lower expression in brain subregions and gonads. 11 beta-HSD1 mRNA was below the level of detection in the murine colon. 11 beta-HSD1 mRNA levels in kidney was higher in males than in females, but in contrast to the rat, there was no sexual dimorphism in the mouse liver. Although males and females showed different mRNA levels in the kidney, there was no sex difference in 11 beta-HSD enzyme activity. Thus, despite the high inter-species conservation of 11 beta-HSD1, there are clear species and tissue-specific differences in its expression. PMID- 7873450 TI - Regulation of c-fos expression and TGF-beta production by gonadal and adrenal androgens in normal human osteoblastic cells. AB - Although the role of estrogens in bone formation is becoming clarified, the function of androgens in this process remains to be defined. Consequently, we have explored the mechanism of action for both gonadal and adrenal androgens in normal human osteoblastic (hOB) cells, which are responsible for the synthesis and mineralization of bone. Changes in the steady-state mRNA levels for two nuclear proto-oncogenes (c-fos and c-jun) and one cytokine (TGF-beta 1) were quantified in response to short (30 min) and long (24-48 h) treatments of these cells with physiologic concentrations of steroids. In addition, the levels of TGF beta protein in the hOB cells conditioned-media were measured using a bioassay. The results indicated that neither 10 nM dihydrotestosterone, 10-20 nM testosterone, nor 10-100 nM androstenedione had a significant effect on the steady-state levels of c-fos, c-jun, or TGF-beta 1 mRNAs. Interestingly, 10-1000 nM dehydroepiandrosterone (DHEA) and 1-10 microM DHEA-sulfate rapidly reduced the steady-state level of c-fos mRNA by 60-80% in a dose-dependent manner within 30 min. In contrast, neither of these adrenal steroids had a significant effect on the message levels for c-jun or TGF-beta 1. Surprisingly, although TGF-beta 1 mRNA levels remained unchanged, the total amount of TGF-beta activity in the hOB cell conditioned-media increased 2-5-fold in response to 24-48 h treatments of the cells with gonadal or adrenal androgens. This increase in TGF-beta activity by DHEA-sulfate was both time- and dose-dependent, and was not blocked by cotreatment with the specific aromatase inhibitor 4-hydroxyandrostenedione (1 microM). Immunoprecipitations of the hOB cell conditioned-media with isoform specific TGF-beta neutralizing-antibodies indicated that TGF-beta 2 was predominantly produced by the cells in response to DHEA-sulfate treatment. These results demonstrate that differences exist between the actions of estrogens and androgens on normal human osteoblasts with regard to the regulation of c-fos expression and TGF-beta production. Moreover, these data suggest that DHEA and DHEA-sulfate may play a distinct role in the regulation of human osteoblast function via the rapid repression of c-fos message levels and the slower increase in TGF-beta 2 protein levels. PMID- 7873451 TI - In vivo and in vitro phosphorylation of the human estrogen receptor. AB - We report here that the human estrogen receptor (hER) overexpressed in Sf9 insect cells is phosphorylated similarly to hER from the human MCF-7 mammary carcinoma cell line. The recombinant and native hER labeled to steady-state with [32P]phosphate were purified to homogeneity using specific DNA-affinity chromatography followed by SDS-gel electrophoresis. Resolution of the hER tryptic digests by reverse phase-high performance liquid chromatography revealed that five [32P]phosphopeptides from the hER expressed in the Sf9 cells had retention times identical to five of the seven [32P]phosphopeptides from the hER in MCF-7 cells. Uniquely, a dephosphorylation of a single 32P-labeled peptide occurred in response to estradiol treatment of MCF-7 cells. In vitro protein kinase assays with the purified recombinant hER revealed that the DNA-dependent protein kinase (DNA-PK) phosphorylated the receptor and induced a decrease in the receptor's mobility as demonstrated by SDS-gel electrophoresis. In contrast, protein kinases A and C did not phosphorylate the purified recombinant hER. These results suggest that in the process of becoming transcriptionally active the estrogen receptor undergoes a dephosphorylation after estrogen-binding and subsequent phosphorylations, in part by the DNA-PK. PMID- 7873452 TI - Steroid 21-hydroxylase in the kidney: demonstration of levels of messenger RNA which correlate with the level of activity. AB - Steroid 21-hydroxylase activity was assayed in low-speed supernatants prepared from whole cell homogenates of mouse and rat tissues. Kidney supernatants had an activity which was approximately 2-5% that of adrenal preparations while heart muscle was found to be without 21-hydroxylase activity. When the enzyme kinetics were characterized, both adrenal and kidney low-speed supernatants demonstrated saturation kinetics, but with very different Vmax and Km values. Using polymerase chain reaction amplification after reverse transcriptase synthesis of cDNA from isolated RNA (RT-PCR), we found low levels of mRNA for steroid 21-hydroxylase in mouse kidney, but none in heart muscle. Thus, extra-adrenal steroid 21 hydroxylase activity in the kidney may be mediated by the same enzyme as found in adrenals. PMID- 7873454 TI - Microbial transformation of steroids--IX. Purification of progesterone hydroxylase cytochrome P-450 from Phycomyces blakesleeanus. AB - Progesterone hydroxylase cytochrome P-450 was purified to homogeneity from Phycomyces blakesleeanus microsomes by a four step procedure. An M(r) value of 60,000 was determined for this protein by SDS-PAGE. The DEAE-cellulose and Blue-1 MIMETIC affinity fractions gave major peaks at 452 nm in a dithionite-reduced, carbon monoxide, difference spectrum. NaIO4-dependent progesterone hydroxylation was obtained by the pure enzyme without NADPH and NADPH-cytochrome P-450 reductase. NADPH-dependent hydroxylation required the addition of other Phycomyces microsomal proteins present in the Blue-1 fraction. PMID- 7873453 TI - Estrone formation from dehydroepiandrosterone in cultured human breast adipose stromal cells. AB - The metabolism of dehydroepiandrosterone (DHA) and androstenedione (A-dione) was studied in cultured human adipose stromal cells obtained from breast tissue of six premenopausal patients undergoing reduction mammoplasty. Cells were maintained in culture in the presence of 10% fetal bovine serum. Studies were carried out during the proliferative and confluent phases of culture with radiolabelled substrates (2 microCi, 10 nM). During the early phases of replication 7 alpha-hydroxydehydroepiandrosterone (7 alpha-OHDHA) was formed from DHA. As the cells reached confluence, the major metabolite of DHA in cells from all patients was A-dione indicating the presence of 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD). The conversion of DHA to A-dione was variable among patients when cells were confluent with 30-80% of substrate being metabolized to this product. Adipose stromal cells synthesized estrone (E1) from DHA once A-dione formation was established. Under basal conditions E1 was obtained in cells from three of the six patients examined with up to 36% substrate converted to this product. Dexamethasone (Dex 10(-7) M) stimulated E1 formation in cells from all subjects with up to 50% of substrate being converted. Parallel studies comparing the conversion of DHA with A-dione to E1 revealed that as the cells became confluent, E1 formation from both substrates was similar. The pattern of steroid metabolism was also examined in primary culture and in subculture. Passage 1 cells continued to form A-dione as a major metabolite of DHA, and did not revert to the pattern of metabolism found in primary cells during the early stages of replication, when 7 alpha-hydroxylation predominated. Human adipose stromal cells actively metabolize DHA, producing 7 alpha-OHDHA, A dione and E1 as principal metabolites. Changes in the circulating levels of DHA may directly influence the formation of E1 in peripheral tissues. This source of E1 will be modulated by factors controlling 3 beta-HSD and aromatase activities. PMID- 7873455 TI - Treatment of advanced breast cancer with formestane. AB - A total of 147 postmenopausal or postoophorectomy patients with advanced breast cancer resistant to standard endocrine therapies were treated with the potent aromatase inhibitor formestane (Lentaron). Among those available for assessment (n = 143), 32 (22%) had a partial response, while another 28 (20%) had stabilization of previously progressive disease. Patients responded to formestane irrespective of whether they had responded to, or failed to respond to, tamoxifen, medroxyprogesterone acetate, aminoglutethimide and trilostane. Toxicity was minimal. We conclude that formestane is an effective and non-toxic therapeutic agent for the treatment of women with advanced breast cancer. PMID- 7873456 TI - Formestane: effective therapy in postmenopausal women with advanced breast cancer. AB - Aromatase inhibitors are a useful therapeutic option in the management of endocrine-dependent advanced breast cancer. Formestane (Lentaron) is the first irreversible aromatase inhibitor to be extensively investigated. In a phase II study to determine the effects of formestane on serum estradiol and urinary 17 hydroxycorticosteroid (17-OHCS) levels and to evaluate its clinical activity, 72 postmenopausal patients with advanced breast cancer were given formestane 250 mg intramuscularly every 2 weeks. Of 66 patients fully evaluable, 56 were estrogen receptor (ER) positive, and 43 had a disease-free interval > or = 2 years. Metastases were assessable in soft tissue (53%), bone (53%) and viscera (47%); 34 patients had 1, 32 had > or = 2 metastatic lesions. Serum estradiol levels fell significantly (p < 0.01) after 2 weeks and remained unchanged thereafter, whereas urinary 17-OHCS levels did not change during treatment. Objective responses were obtained in 19 patients (29%), of whom 8 had complete response. In relation to disease sites, similar responses were obtained in soft tissue (33%) and viscera (30%), whereas response in bone was 18%. The overall tolerability of formestane was satisfactory, and only two patients complained of local side effects. We conclude that formestane is an effective aromatase inhibitor in postmenopausal patients with hormone-dependent breast cancer, and does not interfere with adrenal steroidogenesis. PMID- 7873457 TI - Comparison of the selective aromatase inhibitor formestane with tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer. AB - A total of 409 postmenopausal patients with advanced metastatic breast cancer were randomized to receive either formestane (Lentaron) 250 mg every 2 weeks by intramuscular injection, or tamoxifen 30 mg/day orally. Treatment continued until tumor progression. The groups were well matched for pretreatment characteristics including age, performance status, hormone receptor status (patients with known negative receptor status of their primary tumor were excluded), site and extent of metastases, disease-free interval, and previous primary and adjuvant therapy. Patients were assessed for antitumor efficacy at 3-monthly intervals using UICC criteria. Of the 348 patients evaluable for response, 33% had an objective response to formestane (14 complete and 43 partial responses), while 37% had an objective response to tamoxifen (10 complete and 54 partial responses). Median duration of response was 15 months for formestane and 20 months for tamoxifen; survival was 35 and 38 months respectively. There were no statistically significant differences between the treatments for all these variables, but time to disease progression and time to treatment failure significantly favoured tamoxifen. Systemic tolerability was excellent for both treatments. Local side effects due to intramuscular injection of formestane were mild and transient. In this comparative trial of first-line therapy for advanced breast cancer, formestane gave results comparable to tamoxifen for both efficacy and tolerability. We conclude that formestane is an effective and well tolerated addition to the therapeutic options available for the treatment of postmenopausal women with advanced breast cancer. PMID- 7873458 TI - The role of pamidronate. PMID- 7873459 TI - Intravenous pamidronate: infusion rate and safety. AB - In view of previous animal studies showing that pamidronate (Aredia) can cause renal damage, and human data indicating that pamidronate in doses of 60-90 mg is more effective in the control of tumor-induced hypercalcemia than when given at lower doses, we decided to investigate whether pamidronate 90 mg infused over 60 minutes at weekly intervals had any adverse effects on renal function in patients with bone metastases. Twelve patients, 7 female (all with breast cancer) and 5 male (4 with prostate cancer, 1 with bladder cancer) were entered into the trial. Each patient received weekly intravenous infusions of pamidronate 90 mg in 250 ml normal saline over 60 minutes for 4 weeks. 51Cr-EDTA clearances showed no significant changes in renal function. Urinary N-acetyl-B-D glucosaminidase/creatinine ratios fluctuated considerably, but no consistent changes were found. No patient with a normal level of urinary beta 2 microglobulin had elevated levels at the end of the trial. Serum creatinine levels did not change significantly, though 1 patient had a corrected serum calcium level of < 2 mmol/L on a single occasion on day 8. No evidence of renal toxicity was detected. However, the possibility that neprohtoxicity would ultimately appear cannot be excluded, and these favourable short-term results cannot be extrapolated to patients with impaired renal function. PMID- 7873460 TI - Aromatase inhibition: basic concepts, and the pharmacodynamics of formestane. AB - Aromatase inhibition is an established therapeutic option for the treatment of postmenopausal breast cancer, and current developments indicate that it will become more important over the coming years. Aromatase is a cytochrome P450 enzyme, and may be inhibited in 2 ways. First, non-steroidal inhibitors may interact directly with the prosthetic haem group of the enzyme; second, substrate analogues may compete with the normal androgen substrate for the enzyme binding site. Development of the former group has been more problematic with regard to specificity because of the widespread importance of cytochrome P450 enzymes in physiology. The pre-eminent substrate analogue is 4-hydroxyandrostenedione (formestane, Lentaron). As well as competing for the enzyme binding site, formestane is converted to a reactive intermediate which permanently inactivates the bound enzyme molecule. This mechanism is termed suicide inhibition, and has the benefit of being highly selective and of long-lasting effectiveness. In patients, formestane has been found to exert no significant effects on hormone synthetic pathways other than that of estrogen synthesis. A minor androgenic component of the drug is reflected in a dose-related fall in serum levels of sex hormone binding globulin, but this is not associated with clinical androgenic side effects. Following a series of endocrine studies a dose of 250 mg intramuscularly every 2 weeks has been selected as optimal for treatment. At this dose formestane is well tolerated and of good clinical efficacy. PMID- 7873461 TI - Delayed progression of bone metastases with pamidronate therapy in breast cancer patients: a randomized, multicenter phase III trial. AB - A total of 295 patients with lytic bone metastases from breast cancer were randomized to receive chemotherapy or chemotherapy plus pamidronate (Aredia) 45 mg intravenously every 3 weeks. Primary endpoints were time to progressive bone disease (evaluated by blind extramural review), and improvement in pain (according to a 6-point self-assessment scale). Secondary endpoints included incidence of bone-related complications (pathological fractures, tumor-induced hypercalcemia, need for radiotherapy), sclerotic response of lytic lesions, WHO performance status, and analgesic score. Median time to bone progression was 249 days and 168 days in the pamidronate and control groups respectively (p = 0.02). Marked improvement in bone pain was observed in 44% of patients receiving pamidronate compared to 30% in controls (p = 0.025). With respect to secondary endpoints, pamidronate reduced the need for radiotherapy (66 times vs. 82 times in controls), and median time to radiotherapy was 697 days with pamidronate, 571 in the control arm. No severe adverse reactions or worsening of chemotherapy induced toxicities were observed during 1598 pamidronate infusions. We conclude that intravenous pamidronate is well tolerated, significantly prolongs time to progressive bone disease, and significantly improves bone pain in patients with osteolytic metastases from breast cancer. PMID- 7873462 TI - Effect of pamidronate on the mechanical properties of canine bone. AB - Pamidronate (Aredia) has been used in the treatment of hypercalcemia of malignancy, in Paget's disease of bone, and in osteoporosis to prevent bone resorption. In a 3-month study, intermittent intravenous infusions of pamidronate in dogs did not change the mechanical properties of cortical bone, either in torsion or bending. However, such treatment increased the compressive stiffness and torsional strength of trabecular specimens taken from vertebrae. In a 1-year study, oral administration of pamidronate at various doses produced a linear increase in the elastic modulus of trabecular bone with the square root of the dose and no change in cortical bone. Finally, in a 2-year study (1 year on pamidronate followed by 1 year recovery), no differences were found in the mechanical properties of whole bone whatever dose was given. PMID- 7873463 TI - Use of a bisphosphonate (pamidronate) to modulate fracture repair in ovine bone. AB - Bisphosphonates influence the morphology and mechanical properties of bones in growing rats, but their effects on fracture repair are not well documented. This study tests the hypothesis that bisphosphonates will modulate the remodelling phase of fracture repair, influencing the mechanical properties of healing bone. The effects of a bisphosphonate (pamidronate, Aredia) on the healing of a 3 mm osteotomy gap in the mid-diaphysis of the tibia, under rigid unilateral external fixation, were evaluated using 2 groups of 6 skeletally mature sheep. The repair process was evaluated weekly for 12 weeks using conventional radiographs, dual photon absorptiometry, and fracture stiffness measurements. The animals were then killed and the torsional stiffness and strength of the tibiae measured. More prolific callus formation, with an associated rise in the rate of bone mineral content, was observed in the treated group. There were no differences in in vivo fracture stiffness or postmortem torsional stiffness between the 2 groups, but torsional strength was greater in the treated group. Callus remodelling was reduced but not arrested in the treated group. Bisphosphonates act to reduce callus remodelling, leading to an increased amount of bridging callus and therefore strength. This study indicates that pamidronate has no adverse effects on the restoration of the mechanical integrity of a long bone after fracture. PMID- 7873464 TI - Formestane in the treatment of advanced postmenopausal breast cancer. AB - In a phase II study, 91 women with advanced breast cancer received formestane (Lentaron) 500 mg intramuscularly every 2 weeks for 6 weeks, and then 250 mg every 2 weeks thereafter; all were either postmenopausal or surgically oophorectomized, and most had received previous hormonal treatment and/or chemotherapy. Complete or partial response was seen in 23%, disease stabilization in 29%. Disease-free interval and site of metastatic lesions did not significantly affect response. Patients who had previously responded to tamoxifen showed the best results with formestane. Side effects were generally mild and transient; only 3 patients had to discontinue treatment. Serum estradiol and estrone levels fell significantly after 2 weeks' treatment, and remained suppressed; there were no significant changes in serum cortisol, blood parameters, and liver and kidney function. Formestane thus appears to be an effective, specific and well-tolerated aromatase inhibitor for the treatment of advanced postmenopausal breast cancer. PMID- 7873465 TI - Neurohormonal mechanisms and the role of angiotensin-converting enzyme (ACE) inhibitors in heart failure. AB - Clinical evidence accumulated over the past decade suggests that neurohormonal mechanisms significantly influence the pathogenesis and eventual outcome of congestive heart failure (CHF). Pharmacologic modulation of this neuroendocrine activity can, consequently, be expected to improve patient prognosis. Results of several recent clinical trials--the Studies of Left Ventricular Dysfunction (SOLVD), the second Veterans Administration Cooperative Vasodilator Heart Failure Trial (VH eFT-II), and the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS)--provide substantial evidence that addition of the angiotensin converting enzyme (ACE) inhibitor enalapril to conventional therapeutic regimens can significantly reduce mortality and improve prognosis in patients with all grades of heart failure. Moreover, data from all three trials confirm the involvement of neurohormonal systems in the development and progression of CHF and suggest that the beneficial effects of enalapril in heart failure may in part be due to the suppression of this neurohormonal activity. It is now apparent that some form of neurohormonal activation is present early in the course of the disease before the emergence of overt heart failure symptoms. On the basis of such findings, it would seem that early introduction of therapy targeted at neurohormonal influences may well become a central component of any future CHF treatment program. PMID- 7873466 TI - Clinical pharmacokinetics of nitrates. AB - The pharmacokinetics of organic nitrates are discussed with emphasis on the possible clinical relevance. For glyceryl trinitrate, the measurement of plasma concentrations is very difficult. Its pharmacokinetics are unusual, with a very rapid disappearance from plasma, and large intraindividual and interindividual variations. After oral administration, there seems to be a very extensive first pass hepatic extraction and the plasma concentrations are often below the detection limit; after sublingual administration, glyceryl trinitrate appears in plasma. With transdermal glyceryl trinitrate controlled-release systems, plasma concentrations of glyceryl trinitrate can be maintained over 24 hours, although with fluctuations and important intraindividual and interindividual variability. After administration of glyceryl trinitrate via different routes, glyceryl dinitrates and mononitrates are present in plasma. The pharmacokinetics of isosorbide dinitrate are somewhat easier to understand. The substance disappears less rapidly from the plasma than does glyceryl trinitrate. After oral administration, there is also a hepatic first-pass extraction; the plasma concentrations can be prolonged by administering slow-release products. Sublingual administration leads to higher plasma concentrations than oral administration. Isosorbide dinitrate is metabolized in the organism to isosorbide 5-mononitrate and isosorbide 2-mononitrate, which both have vasodilator activity: after administration of isosorbide dinitrate, the mononitrates, and mainly the 5 mononitrate, reach very high concentrations in plasma. Isosorbide 5-mononitrate has been studied in its own right as an antianginal agent: it is completely absorbed after oral administration; it has a half-life of around 4 hours, and oral standard and controlled-release formulations have been extensively studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873468 TI - Nitrates for unstable angina. AB - The term unstable angina encompasses heterogeneous clinical syndromes. Fissuring of an atherosclerotic coronary artery plaque with superimposed platelet deposition, with or without additional thrombus formation, is invariably responsible for a prolonged episode of angina at rest, increasing frequency of angina at rest, or with minimal exertion of less than 4 weeks in duration and early postinfarction angina. Plaque progression, rather than plaque fissuring, is the most likely mechanism for progressive reduction in walking distance due to angina in patients who previously have stable angina. Coronary artery spasm is responsible for Prinzmetal's variant angina, but its exact role in other forms of unstable angina is unknown. The mainstay of treatment of unstable angina (prolonged episode of angina at rest and recent onset angina at rest, or with minimal exertion with a crescendo pattern) is aspirin, heparin, or both. Both aspirin and intravenous (i.v.) heparin or their combination reduce early mortality and the incidence of acute myocardial infarction in patients hospitalized with unstable angina. However, these agents do not promptly relieve chest pain. There are no placebo-controlled studies evaluating the usefulness of nitrates in unstable angina. In open-label studies, continuous therapy with i.v. nitroglycerin (NTG) for 24 hours or longer has been shown to relieve chest pain in patients with rest angina refractory to therapy with other antianginal agents, including long-acting nitrates. Recurrence of chest pain in patients receiving i.v. NTG is a common problem and probably represents development of pharmacologic tolerance, but this can be overridden by dose escalation; protracted tolerance during short-term use of i.v. NTG is usually not a problem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873469 TI - Nitrates in silent ischemia. AB - In recent years it has become clear that episodes of transient myocardial ischemia commonly occur in patients with coronary artery disease in the absence of chest pain or angina equivalent. These episodes of "silent myocardial ischemia" are particularly well documented during continuous ambulatory electrocardiographic monitoring in daily life. Evidence suggests that these episodes represent true ischemia, and appear to be a marker of unfavorable outcome. While the pathophysiology is not completely understood, it appears as though the mechanisms of angina and silent ischemia are the same. Both forms of ischemia respond to conventional antianginal medication. While long-acting nitrates are effective in reducing or preventing myocardial ischemia, because of their propensity to cause tolerance they should be used intermittently and in association with either beta-blockers or calcium antagonists. Nitrates are safe and comparatively inexpensive, and will continue to play an important role in the treatment and prevention of angina. However, in the light of current knowledge, there is no specific indication for the treatment of silent ischemia by nitrates. PMID- 7873470 TI - Regression of left ventricular hypertrophy and improvement of renal hemodynamics in hypertensive patients treated with quinapril. AB - Of 17 patients with mild to moderate essential hypertension, 8 showed echocardiographic evidence of left ventricular hypertrophy. Cardiac and renal function evaluated by glomerular filtration rate (GFR) were studied in all patients before and after 20 weeks of quinapril treatment. Systolic pressure decreased from 174.7 +/- 16.7 to 131.7 +/- 7.7 mmHg (p < .0001) and diastolic pressure decreased from 101.8 +/- 9.8 to 80 +/- 4.3 mmHg (p < .0001). Left ventricular mass index decreased in the eight patients with left ventricular hypertrophy (p < .01). Basal values of GFR were lower than normal in 41% of all patients; GFR increased significantly after 20 weeks of treatment (from 96.5 +/- 32.3 to 108.6 +/- 31.12 ml/min, p < .01); it decreased in only one patient. Patients reported few adverse effects to quinapril, and no important clinical laboratory abnormality was observed. Quinapril not only lowered arterial pressure, but it had a distinct effect on regression of left ventricular hypertrophy and favorable effects on renal function. PMID- 7873471 TI - Effects of ranolazine on left ventricular regional diastolic function in patients with ischemic heart disease. AB - To assess the effects of ranolazine, a new antiischemic drug, on regional myocardium of the left ventricle, left ventricular (LV) hemodynamic and angiographic data were obtained in 15 patients with previous transmural myocardial infarction before and after intravenous infusion of ranolazine (200 or 500 micrograms/kg body weight). LV angiogram was analyzed by the area method and was divided into six segments. Regional LV segments were classified as normal (perfused by intact coronary vessels, n = 20), ischemic (perfused by stenotic vessels but without ECG evidence suggesting myocardial necrosis, n = 25), or infarcted (total coronary occlusion and with the ECG evidence for necrosis, n = 45). Regional area fractional shortening, peak filling rate, and segmental wall motion during isovolumic relaxation period were analyzed. After ranolazine, regional area fractional shortening was unchanged in all segments. However, regional peak filling rate was decreased in the normal segments (1499 +/- 315 to 1368 +/- 303 mm2/sec, p < 0.05). In the ischemic segments, by contrast, the administration of ranolazine significantly increased the regional peak filling rate (1050 +/- 410 to 1133 +/- 439 mm/sec, p < 0.05) and regional wall lengthening during the isovolumic relaxation period (0.9 +/- 4.1% to 2.8 +/- 5.7% of end-diastolic segmental area, p < 0.05), which indicates an improvement of regional diastolic function. Infarct segments were little affected by ranolazine. Thus, ranolazine improves diastolic function of the noninfarcted myocardium under chronic ischemic conditions and also may exert a mild negative lusitropic effect on the normal myocardium, although the former beneficial effect appears to be more clinically important.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873467 TI - Mechanisms of action of nitrates. AB - Glyceryl trinitrate, isosorbide dinitrate, and isosorbide-5-mononitrate are organic nitrate esters commonly used in the treatment of angina pectoris, myocardial infarction, and congestive heart failure. Organic nitrate esters have a direct relaxant effect on vascular smooth muscles, and the dilation of coronary vessels improves oxygen supply to the myocardium. The dilation of peripheral veins, and in higher doses peripheral arteries, reduces preload and afterload, and thereby lowers myocardial oxygen consumption. Inhibition of platelet aggregation is another effect that is probably of therapeutic value. Effects on the central nervous system and the myocardium have been shown but not scrutinized for therapeutic importance. Both the relaxing effect on vascular smooth muscle and the effect on platelets are considered to be due to a stimulation of soluble guanylate cyclase by nitric oxide derived from the organic nitrate ester molecule through metabolization catalyzed by enzymes such as glutathione S-transferase, cytochrome P-450, and possibly esterases. The cyclic GMP produced by the guanylate cyclase acts via cGMP-dependent protein kinase. Ultimately, through various processes, the protein kinase lowers intracellular calcium; an increased uptake to and a decreased release from intracellular stores seem to be particularly important. PMID- 7873472 TI - Blockade of ATP-sensitive potassium channels by 5-hydroxydecanoate suppresses monophasic action potential shortening during regional myocardial ischemia. AB - We tested 5-hydroxydecanoate (5-HD), a specific blocker of ATP-sensitive potassium channels (IK.ATP), to determine if mitigates electrophysiologic changes produced by regional myocardial ischemia in vivo. A sequence of 5-minute occlusion of the distal LAD and 30-minute reperfusion was repeated while recording the monophasic action potential (MAP) and bipolar electrogram (EG) from the epicardial center of the ischemic myocardium in anesthetized dogs. 5-HD (30 mg/kg, i.v.) or glibenclamide (0.15 or 0.3 mg/kg, i.v.) was administered before the third occlusion, and the data were compared to the second occlusion data. 5 HD did not affect baseline MAP duration at 90% and 50% repolarization (APD90, APD50) before LAD occlusion but suppressed occlusion-induced shortening of APD90 (16 +/- 2% during the second occlusion vs. 5 +/- 3% during the third occlusion, n = 8, p < 0.01) and APD50 (16 +/- 3% vs. 10 +/- 3%, n = 8, p < 0.05). Pretreatment with glibenclamide also suppressed occlusion-induced MAP shortening and eliminated an additional effect of 5-HD (n = 3). 5-HD did not affect the occlusion-induced increase in duration and activation time of EG. 5-HD, as well as glibenclamide, suppressed regional ischemia-induced MAP shortening, probably by blocking activation of IK.ATP, without affecting conduction delay. These differential effects of 5-HD on repolarization and conduction during the early phase of regional ischemia might have the potential to suppress reentrant ventricular arrhythmias. PMID- 7873473 TI - J curve in antihypertensive therapy--does it exist? A personal point of view. AB - Coronary flow is maintained in the face of changing perfusion pressure (approximates to diastolic blood pressure [DBP]) by the process of autoregulation. A normal coronary artery is able to dilate fivefold (coronary flow reserve of 5); by contrast, coronary flow reserve falls in the presence of left ventricular hypertrophy [LVH] and/or coronary artery disease. Thus a fall in DBP that is normally well tolerated causes a fall in coronary flow, ECG changes, and left ventricular dysfunction in the presence of LVH and coronary artery disease. Such high-risk patients exhibit a J-curve relationship between DBP and death from coronary artery disease; lowering DBP (phase 5) to below the mid 80s would be imprudent in such patients. PMID- 7873475 TI - Amiodarone as a first-line drug in the treatment of atrial fibrillation: the protagonist viewpoint. AB - The endpoint of pharmacologic therapy in patients with recurrent paroxysmal atrial fibrillation or in patients with chronic atrial fibrillation successfully cardioverted is to prevent recurrences. Recent studies have cautioned against the use of sodium channel blockers (class I agents) in terms of safety. A number of patients with atrial fibrillation have coronary artery disease and the use of class I agents may be of concern, as suggested by the CAST trial. Recently a concern was also raised, regarding the safety of quinidine following cardioversion of atrial fibrillation. In patients with congestive heart failure on antiarrhythmic therapy, the SPAF trial has shown an increase in cardiac mortality and arrhythmic deaths. In this review a case is made in favor of the use of low-dose amiodarone as a first-line agent in patients with atrial fibrillation. Amiodarone is a potent antiarrhythmic agent with little if any negative inotropic effect and, therefore, is the agent of choice in patients with heart failure. In patients with coronary artery disease, the antianginal properties may be useful, and recent studies have shown a decrease in sudden death in the amiodarone group. Therefore, a number of advantages do exist in favor of the use of amiodarone as a first-line drug, at least in selected indications. PMID- 7873474 TI - Reassessment of digoxin and other low-dose positive inotropes in the treatment of chronic heart failure. AB - Digoxin and other low doses of drugs that have inotropic properties may have an important role to play in the therapy of patients with chronic heart failure. There is convincing evidence that digoxin is effective in relieving the signs and symptoms of heart failure due to systolic dysfunction. While earlier results with some of the other agents have been disappointing, recent data suggest that a reevaluation of these agents is necessary. There is now compelling evidence that lower doses of these agents may be clinically useful without necessarily having any significant hemodynamic effects. The recent experience with vesnarinone is especially promising in showing that therapy with these agents may improve survival in addition to improving clinical status. It is becoming recognized that hemodynamic activity should not necessarily be a prerequisite for clinical utility for those agents. The neuroendocrine and electrophysiologic effects of many of these agents, including digitalis, remain incompletely characterized and may play an important role in their therapeutic benefit. It appears that certain drugs that have inotropic properties may be effective only when their inotropic effects are not readily demonstrated. Further research into the appropriate mechanisms of action and proper dosing of these drugs may lead to a renewed interest in the use of positive inotropes for chronic heart failure. PMID- 7873476 TI - Low-dose amiodarone should not be the first-line treatment for atrial fibrillation. AB - Although amiodarone is the most effective antiarrhythmic agent for maintaining sinus rhythm in patients with atrial fibrillation, it is generally used as the drug of the last resort in the United States. This is because long-term amiodarone therapy can potentially cause serious noncardiac side effects, such as pulmonary fibrosis, thyroid dysfunction, hepatitis, and neurotoxicity. Furthermore, it may also cause adverse interaction with digoxin, coumadin, and other antiarrhythmic drugs. Atrial fibrillation is frequently associated with a variety of cardiac disease, and its triggering factors vary among patients. Treatment strategy should be tailored to each individual patient according to the clinical presentation, concomitant disease, left ventricular function, and response (efficacy and side effects) to each drug regimen. PMID- 7873478 TI - Radiotherapy in a district general hospital. PMID- 7873477 TI - Peripheral vein plasma endothelin-1 levels during coronary angioplasty increase only in normotensive patients. PMID- 7873479 TI - Does neo-adjuvant chemotherapy have a role in cervical cancer? PMID- 7873480 TI - Results of radical radiotherapy in carcinoma of the uterine cervix stage I-III. AB - A retrospective analysis is described of 271 diagnosed cases of carcinoma of the uterine cervix who were treated with radical radiotherapy between January 1987 and July 1988 at the Institute Rotary Cancer Hospital. The mean age at presentation was 49 years and 89% of the tumours were FIGO Stage II and III. The median duration of follow-up was 60 months. The early cases were treated with two intracavitary insertions of 34 Gy each to point A with a Selectron LDR intracavitary system, followed by 36 Gy external radiotherapy to the parametrium. Late stage disease was treated with 50 Gy of external radiotherapy, followed by a single intracavitary insertion of 30 Gy to point A. To compensate for the higher dose rate of the Selectron (180 cGy/h) a dose reduction factor of 15% was applied over the intracavitary dose. There were 2.5% and 4.7% of late Grade III bladder and bowel complications, respectively, requiring surgical intervention. There was no relationship between haemoglobin level at diagnosis and the development of late complications. The actuarial 5-year survivals were 65%, 63% and 35% for Stages I, II and III disease, respectively. This study from the Indian subcontinent shows the effectiveness of radiotherapy in Stages I, II and III carcinoma of the uterine cervix, with acceptable morbidity rates. PMID- 7873481 TI - Incidence of second brain tumours after pituitary irradiation in Edinburgh 1962 1990. AB - Two hundred and ninety-six patients irradiated for pituitary adenoma in Edinburgh between 1962 and 1990 were reviewed. The number of subsequent tumours was noted. The expected incidence of tumours was estimated, based on data from the Scottish Cancer Registry, for an age and sex matched population. One malignant brain tumour was found; the expected incidence was 0.3 (95% CI 0-12). One meningioma was reported. Thirty non-CNS tumours were found, compared with an expected incidence of 17.5 (95% CI 12-26). We see no reason at present to alter our practice as a result of radiation induced neoplasia in this group, although close follow-up continues. PMID- 7873482 TI - Intraperitoneal adjuvant immunochemotherapy in operable gastric cancer with serosal involvement. AB - Since the peritoneal cavity is the most common site of initial recurrence in patients after surgery for gastric cancer, an intraperitoneal (IP) adjuvant treatment was tested in patients with resected gastric cancer with serosal involvement. Between March 1986 and September 1991, 44 consecutive patients with resected T3/T4-N0/N+ gastric cancer were given an IP combination, including cisplatin or carboplatin, etoposide, and alpha interferon-2b. The overall survival of these patients was compared with that observed in 47 historical controls (admitted to the same institutions from 1983 to 1986) with similar prognostic characteristics, who had not received adjuvant treatment after surgery. No major complication relating to the IP route was observed. Mild to moderate abdominal pain occurred in nine patients. Grade 3-4 myelotoxicity occurred in 14 patients. Interferon had to be reduced in five patients and suspended in one because of severe fatigue. Emesis occurred in 23/28 patients given cisplatin and 9/16 given carboplatin. At the time of this analysis (September 1992) median follow-up was 42 months (range 12-78) in the group receiving IP treatment, and 97 months (range 74-128) in the historical controls. There had been 20 deaths among treated patients compared with 36 in the control group. The 5-year estimated survival rate was significantly better in the patients who received IP adjuvant treatment (44% +/- 9 versus 23% +/- 6; P = 0.016). Using the Cox proportional hazard model with a backward procedure to correct for the influence of prognostic pretreatment variables, IP treatment again afforded a significant advantage in terms of survival (P = 0.04). Adjuvant IP immunochemotherapy appears to improve prognosis compared with historical controls in patients having operable gastric cancer with serosal infiltration. PMID- 7873483 TI - A 20-year review of haemangiopericytoma in Auckland, New Zealand. AB - The records of all patients registered with a histological diagnosis of haemangiopericytoma in Auckland between 1970 and 1990 were reviewed retrospectively, with the aim of determining the natural history of the disease and the response to various treatment modalities. A total of 24 patients were identified, having a median age of 45 years. Twenty-one patients (87.5%) underwent surgery; the remaining three were deemed to be unfit for surgery. Seven patients (29%) were treated with surgery alone; nine (37.5%) received a radical course of radiotherapy and three (12.5%) received palliative radiation therapy for pain relief and/or dyspnoea. Five patients (21%) received chemotherapy during the course of their disease. Eight of the 24 patients (33%) were alive and disease free, 13 (54%) having died and three (13%) being lost to follow-up. Seven patients (29%) died as a result of metastatic disease. Three of the seven (43%) who were treated with surgery alone are known to be alive and disease free. The three patients who had received palliative radiotherapy, died within 2 months of completing the latter treatment. Five of the nine patients (56%) receiving a course of radical radiotherapy are alive and disease free at present. No local recurrence was noted following surgical excision and postoperative radical radiotherapy, whilst eight (67%) of those initially treated by excision alone developed recurrent disease. None of the patients treated with chemotherapy obtained significant palliation. Results suggest that adequate surgical excision followed by postoperative radiotherapy is effective in controlling haemangiopericytoma and that metastatic disease is at present invariably fatal. The role of chemotherapy needs further investigation. PMID- 7873484 TI - Fertility in patients treated with radiotherapy following orchidectomy for testicular seminoma. AB - This study evaluated the effect of paraaortic and ipsilateral pelvic node irradiation on the fertility of a group of 50 patients with Stage I and II testicular seminoma. Eleven patients were infertile before the start of treatment, and another 23 were unable or unwilling to father a child after radiotherapy. From the remaining 16 patients, 11 pregnancies resulted. It has been shown that fertility can be preserved if the dose to the remaining testis can be reduced to less than 2 Gy. No genetic abnormalities were seen in the offspring of any patient. PMID- 7873485 TI - The development of a massage service for cancer patients. AB - Despite major technological advances in the treatment of cancer, many patients are dissatisfied with conventional biomedical interventions. This is largely because they fail to resolve long term intractable problems such as chronic pain or stress. More emphasis is now being placed on quality of life. This shift in attitude has opened the door for complementary therapies as adjuvants to traditional models of cancer care. Changes within the NHS have facilitated this transition, by the creation of the 'internal market' and the development of central funding to individual clinical directorates. To exploit these opportunities, complementary, therapists must develop new skills and be prepared to adopt NHS standards of assessment to evaluate the efficacy of their work. Standards are a component of 'Quality assurance'. They are observable, achievable and measurable, and contribute towards an acceptable evaluation process. Standards are used by health care purchasers to assess which therapies should be made available to patients within the NHS. This paper describes the development of a massage service that has been integrated into the Hammersmith Oncology Department. The massage standard is seen to be fundamental and essential to the continued development and evaluation of the project. PMID- 7873486 TI - The treatment of low grade lymphoma. PMID- 7873487 TI - Recent developments in radioimmunotherapy. AB - With the advent of monoclonal antibody techniques, there has been renewed interest in RIT as a treatment modality in patients with a variety of tumour types. There has been a considerable research effort to increase understanding of the scientific basis of such therapy at all levels. Antibody, chelator and radioisotope factors are all the subject of research aimed at producing a potent effector system capable of maximal target cell kill with acceptable normal tissue toxicity. Improved knowledge of the host and tumour factors which limit access to the target cell offers the possibility of optimizing targeting and increasing the therapeutic index. Target cell factors that influence response to low dose rate RIT have been elucidated and provide an opportunity to integrate the treatment modality into radical therapy regimens. A number of Phase I and II trials have now been performed in various tumour types. The results have been promising but, as yet, the prospect of radical RIT remains a research goal. Before it can be achieved it will be necessary to improve specific tumour cell targeting and to increase both the initial dose rates and the total dose delivered to tumour deposits. Until such time, it is likely that RIT will be incorporated into multimodality protocols to deliver a moderate (10-20 Gy) tumour boost, or in an adjuvant setting in patients with minimal residual disease. PMID- 7873488 TI - Multifocal inflammatory leukoencephalopathy developing in a patient receiving 5 fluorouracil and levamisole. AB - A single case of multifocal inflammatory leukoencephalopathy, which developed during a course of adjuvant chemotherapy with 5-fluorouracil (5FU) and levamisole is reported. Clinical features developed slowly and were not dramatic; this condition may therefore frequently be missed. PMID- 7873489 TI - An unusual late relapse of metastatic non-seminomatous germ cell tumour. PMID- 7873490 TI - Fatal primary mediastinal non-seminomatous germ cell tumour initially diagnosed as malignant mesothelioma. AB - A patient with a missed diagnosis of a primary mediastinal germ cell tumour is reported. The initial diagnosis of malignant mesothelioma was not compatible with the clinical course. The true diagnosis was reached after the patient had completed a course of palliative irradiation following the development of superior vena cava obstruction. He succumbed to a massive haemoptysis before chemotherapy could begin. PMID- 7873491 TI - Primary bone lymphoma: report of an unusual case with a review of the literature. AB - Primary bone lymphoma is uncommon and usually involves the long bones. We report a patient with involvement of a metacarpal bone, and review the literature. PMID- 7873492 TI - [Development and differentiation of macrophages and their related cells]. AB - In murine, macrophages and their related cells are classified into monocyte derived macrophages, resident macrophages, Ly-1(CD5)-positive macrophages, and dendritic cells. Monocyte-derived macrophages are terminal cells of the mononuclear phagocyte system, differentiate from monocytes which develop via promonocytes from monoblasts in bone marrow, and possess no proliferative capacity under a normal steady state. Monocytic cells first develop in hepatic hematopoiesis in ontogeny and are produced in bone marrow after birth. Monocytes first appear in peripheral blood in the late stage of ontogeny and are constantly produced in the bone marrow throughout adult life. Resident macrophages have a proliferative potential, can be sustained by self-renewal, and are suggested to be derived from colony forming unit-granulocyte/macrophages (CFU-GM) or earlier precursor cells, bypassing the stage of promonocytes and monocytes. In ontogeny, the resident macrophages differentiate from primitive/fetal macrophages which develop in blood islands of the yolk sac. The primitive/fetal macrophages precede the development of monocytic cell series, are distributed into embryonic tissues after the combination of the vitelline vessels to the fetal cardiovascular system, and are circulating in peripheral blood in the early stage of ontogeny. Ly-1-positive macrophages are a minor population residing in the peritoneal cavity, develop in the milky spots, and are suggested to be derived from precursor cells common to those of Ly-1 B cells. Dendritic cells are classified into two major groups; B cell-associated dendritic cells (follicular dendritic cells) and T cell-associated dendritic cells (Langerhans cells, interdigitating cells, veiled cells).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873493 TI - [Differentiation and function of human monocytes]. AB - We found that human monocytes differentiate into macrophages (Mp) by GM-CSF and M CSF. The Mp induced by GM-CSF and M-CSF are different in their morphology, cell surface antigen expression and functions. In the course of that study, we found that IL-4 modulate the differentiation of monocytes induced by GM-CSF and M-CSF. IL-4 alone did not induce the proliferation and differentiation of monocytes. IL 4, however, inhibited the proliferative response of monocytes to GM-CSF. When monocytes were incubated with GM-CSF and IL-4 simultaneously, the cells recovered were non-adherent, non-phagocytic, and did not form rosette with EA. The cells were also negative in nonspecific esterase and showed an appearance of dendritic cells (DC). The DC-like cells expressed CD1, DR, DQ and CD11c, but not CD14, CD71 and 710F. The cells showed strong APC activity in alogeneic and autologous mixed lymphocyte reaction (MLR). When monocytes were incubated with M-CSF and IL-4, TRAP positive multinucleated giant cells appeared. Taken together, these results suggest that IL-4 is a principal factor that control the differential development of human monocytes into DC and multinucleated giant cells. PMID- 7873494 TI - [Prevention of cancer recurrence by infusion of activated autologous lymphocytes]. AB - Activated and expanded autologous peripheral blood lymphocytes by cultivation with immobilized anti-CD3 antibody and IL-2 have been infused to the patients with hepatocellular carcinoma after culative operation as a randomized clinical trial. This study is on-going and primary efficacy endpoints of this study were disease-free survival and overall survival, and the sample size for the study was designed as a minimum of 146 patients. From interim analysis at the second year from start of the study, Eligible cases were 101, 49 cases in treated group and 52 cases in control. Recurrences were confirmed 13 cases from treated group and 22 cases from control group. Minor adverse reaction were observed in 28 cases (57%). PMID- 7873495 TI - [Cultivation and activation of Th1 and Th2 clones]. AB - Murine T helper clones are classified into two subpopulations, Th1 and Th2, according to the cytokines they produce. Immune function is considered to depend which subpopulation is activated by an antigen stimulation. These subpopulations are different from each other in humoral second signal molecules required for their proliferation produced by antigen-presenting cells. Th1 requires IL-12, and Th2 IL-1, indicating that antigen-presenting cells regulate subpopulation responding to some stimulation. These subpopulations are also different in their activation signal transduction pathway mediated by TCR stimulation, suggesting a possibility of a selective activation of these subpopulations. PMID- 7873496 TI - [An efficient methods for the induction of human antitumor effector CD4+ and CD8+ T cells: their application to tumor immunotherapy]. AB - It is an important issues to investigate an efficient methods to induce antitumor effector T cells from peripheral blood lymphocytes of tumor patients for the development of a novel tumor immunotherapy. We established a large scale culture system of human CD4+ helper/killer T cells which have both helper and killer functions. Targeting of CD4+ helper/killer T cells to tumor using anti-CD3 x anti c-erbB-2 mAb caused the lysis of tumor and triggering of IL-2 production. It was also demonstrated that culture of human CD4+ T cells with staphylococcal enterotoxin A (SEA) or IL-12 caused a selective induction of Th1 type of CD4+ helper/killer T cells. IL-12 also revealed a novel effect on CD8+CTL functions. Culture of CD8+ T cells with IL-12 resulted in the augmentation of IFN-gamma production and cytotoxicity. Moreover, culture of tumor-infiltrating lymphocytes with IL-12 caused a marked enhancement of CD8+CTL against autologous tumor cells. These findings suggest that IL-12 will become a useful cytokine for the tumor immunotherapy. In this paper, we will discuss the key role of CD4+ T cells for the induction of antitumor immunity in tumor-bearing host. PMID- 7873498 TI - [Establishment and characterization of a new cell line (KT-COLO-8) derived from a colonic mucinous adenocarcinoma]. AB - We have established a human colonic carcinoma cell line, designated KT-COLO-8, derived from cancerous ascites of a 64-year-old male patient who had mucinous adenocarcinoma of the transverse colon. The cells have been cultured with RPMI 1640 medium supplemented with 10% fetal bovine serum. They grew in vitro free floating and formed sheet-like clusters as large as 2-3 mm in diameter. Population doubling time for the cells was 48 hours. The chromosome number ranged from 48 to 50. The Q-band analysis revealed abnormal karyotype with three marker chromosomes including 1p-, 4q- and 5q-. The cells produced and released high level of carcinoembryonic antigen (CEA) in the conditioned medium. Percentage of CEA positive cells was 98%. An aggregation assay revealed that 80% of the cells dissociated into single cells aggregated within 30 min. The self aggregation of the cells was completely inhibited only by anti-CEA monoclonal antibody, suggesting that the cluster formation of KT-COLO-8 cells was dependent on CEA molecules. PMID- 7873497 TI - [Establishment and characterization of a human breast cancer cell line, OCUB-1]. AB - We established new human breast cancer cell line, OCUB-1 derived from the pleural effusion of 53-year old female with recurrent breast cancer. Two sub-cell lines were also established with cloning technique from OCUB-1. Investigating the differences of characteristics between OCUB-1M and 1F, OCUB-1M shows a monolayered growing and OCUB-1F grows in floating. OCUB-1M and 1F revealed Modo 84 and 41 by chromosomal analysis and flow cytometric analysis showed OCUB-1M had twice amount of DNAs as -1F. OCUB-1M revealed higher expression of E-cadherin and laminin receptor against-1F, and activity of 92kDa type IV collagenase could be seen only in OCUB-1M. Estorogen and progesteron receptor were negative in either OCUB-1M and -1F, and no production of tumor markers in the spent media (CEA, CA19 9, CA15-3 and NCC-ST439) was detected in both cells. Both cells could be hetero transplanted in nude mice, but they showed different histology. PMID- 7873499 TI - [Study on the establishment of erythropoietin producing human renal cell carcinoma heterotransplanted to nude mice]. AB - We conducted the establishment of erythropoietin (Epo) producing human renal cell carcinoma heterotransplanted in nude mice (JRC 901) and analysed its histopathological and biological characteristics. Regarding to histopathological analysis, JRC 901 showed renal cell carcinoma with granular cell subtype, alveolar pattern and grade II malignancy. In an effort to the electron microscopic analysis, JRC 901 showed renal cell carcinoma with microvilli, rich lipid droplets and mitochondria. As to the tumour doubling time, the JRC 901 showed 14.81 days in a logarithmic phase. As to the karyotype, the JRC 901 showed human, 46, XY, -11, 8p+, 17q-, +mar. After tumour inoculation to the nude mice, the blood level of Epo increased at 5 weeks, and its level reached at 485.2 mU/ml at 12 weeks after tumour inoculation. Furthermore, immunohistochemical staining using anti-Epo showed positive staining within cytoplasm of JRC 901. Moreover, the production of Epo was observed in the level of mRNA (264 bp) using RT-PCR method. We conclude that the JRC 901 is a human renal cell carcinoma heterotransplantable to nude mice and this tumour produce the Epo after tumour inoculation to nude mice. PMID- 7873500 TI - Long-term passage results of glioma cells and their cell kinetics. AB - The history of brain tumor cultures is old. Established cell lines of brain tumors have increased in recent years, but reports concerning the results of these cultures are few. The results of cultures of gliomas (103 cases of astrocytoma, 9 of ependymoma, 2 of oligodendroglioma and others) obtained from 117 patients treated at our department between 1979 and 1993 were evaluated. The morphological characteristic of these glioma cells were studied, and their cellular kinetics were investigated by flow cytometry. Except for 5 cases, all tumors grew on the flask in the primary cultures, indicating that gliomas were readily cultured. Differences in morphological characteristics and cellular kinetics were not observed in cultures which had been maintained for more than 6 months in astrocytomas of grades II, III, and IV. Cells lines were successively established in 3 cases of glioblastoma and 2 of ependymoma. The results of FCM revealed that those cells which grew well on cultures had high proliferative indices. PMID- 7873501 TI - Establishment of multiple leukemia cell lines with diverse myeloid and/or megakaryoblastoid characteristics from a single Ph1 positive chronic myelogenous leukemia blood sample. AB - Seven cell lines, MOLM-6, -7, -8, -9, -10, -11 and -12, were established from a single blood sample from a patient with chronic myelogenous leukemia (CML) in blastic phase having the Ph1 chromosome abnormality. Based on immunophenotyping, two of these seven cell lines, MOLM-7 and -11, represented the megakaryoblastoid lineage, and the other five cell lines represented two different maturation stages of the myeloid lineage. PMID- 7873503 TI - [Immuno-cryo-ultramicrotomy: its procedures, usefulness, and limitations]. AB - The principle and recent procedures of immunocryoultramicrotomy are presented. In addition, its usefulness and limitations are described. PMID- 7873502 TI - [Establishment of a human colon cancer-derived cell line (KC-1) which produces CEA, CA 19-9 and sialyl SSEA-1(SLX)]. AB - A human colon cancer-derived cell line, KC-1, was established from the surgical specimen of mucinous adenocarcinoma of the colon. The cells grew as monolayers, showing formation of irregular aggregation of cells and pleomorphic nuclei. The doubling time in vitro was 56.6 hours. The cells produced CEA, CA19-9 and sialyl SSEA-1(SLX). Chromosome numbers were distributed between 79 and 83 with many structural abnormalities. A point mutation of the Ki-ras gene in codon 61 (CAA- >CAT) was found. The cells have been subcultured 13 times during these three years. This cell line can be useful for investigations of colon cancer. PMID- 7873504 TI - [Proliferation of fat cells and their proliferation factor]. PMID- 7873506 TI - A comparison between the hemolytic and antibacterial activities of new quaternary ammonium polymers. AB - New quaternary ammonium polymers, which in a previous work had shown relevant antibacterial properties, have been investigated as regards to their hemolytic activity (HA) in comparison with a low molecular weight commercial antibacterial agent, Steramine G (SG). All polymers exhibit negligible, or at most modest, HA at dosages and contact times at which SG is strongly hemolytic. PMID- 7873505 TI - Protein adsorption, lymphocyte adhesion and platelet adhesion/activation on polyurethane ureas is related to hard segment content and composition. AB - Segmented polyurethane ureas with different hard segment content and composition were synthesized using 4,4'-diphenylmethane diisocyanate and polytetramethylene glycols. Using polyols with different molecular weights, it was possible to synthesize polyurethane ureas with either: (i) a constant ratio of urethane to urea bonds; (ii) a constant urethane content; or (iii) a constant urea content. Bulk properties were assessed by dynamic mechanical analysis. Surface properties were estimated by contact angle measurements and streaming potential measurements. Haemocompatibility was evaluated in vitro by measuring the adsorption of human serum albumin (HSA) and fibrinogen (Fg), the adhesion of human peripheral blood lymphocytes (PBL), and the presence of activated platelets on the biomaterial surfaces. Enzyme immuno assays (EIA) have been specially developed for this purpose for the detection of antibody-recognizable plasma proteins and platelet surface membrane proteins. No simple correlation between chemical structure of the polymers and surface properties was found. Parameters of haemocompatibility correlated more closely with hard segment content and chemical composition than with the surface characteristics of the polymers. Adsorption of plasma proteins, adhesion of lymphocytes and the adhesion/activation of platelets were found to increase with increasing hard segment content of the polyurethane ureas. However, the monoclonal-antibody recognisable fibrinogen and the platelet activation were nearly constant with increasing hard segment content, if the urea content was kept constant. PMID- 7873507 TI - Chitin-based poly(urea-urethane)s. AB - Chitins of various origins in DMA-LiCl solution have been reacted with excess 1,6 diisocyanatohexane (three or twelve equivalents per repeating unit) for 4-20 h. The resulting solutions were exposed to water vapor for 2 days and flexible and opaque materials were produced, which upon drying yielded powders whose main characteristics were insolubility in aqueous and organic solvents, remarkable crystallinity, typical infrared spectrum, high N/C ratio (0.287), and a high degree of substitution (0.29). Under the SEM structural features reminiscent of chitin were absent but no thermoplastic behavior was found by differential scanning calorimetry. Chitosan was similarly treated under heterogeneous conditions in anhydrous pyridine, and yielded reaction products with a lower degree of substitution (0.17). With partially hydrolysed chitosan, highly crystalline products were obtained. PMID- 7873508 TI - A new approach to determining homopolymer domain sizes in polycarbonate-polyether dialysis membranes by solid-state NMR. AB - The size of micro-separated domains of polyether (PEO), -[CH2CH2O]n-, and polycarbonate (PC), -[(C6H4)-C(CH3)2-(C6H4)-OCO2]m-, in the dialysis membrane 'Gambrane' have been determined using an advanced solid-state NMR technique which exploits differences in 1H spin diffusion. The characteristic diameter of a PEO domain is 4.8 +/- 1.4 nm and that of PC is 5.2 +/- 1.4 nm with a mixed phase region of 0.8 +/- 0.5 nm. PMID- 7873509 TI - Adsorption of fibrinogen and some other proteins from blood plasma at a variety of solid surfaces. AB - Enzyme linked immunosorbent assay (ELISA) was used for the estimation of protein adsorption from blood plasma at some model solid surfaces. The majority of those surfaces were made in the wells of microtiterplates of polystyrene commonly used for ELISA purposes. Three of the model surfaces were made by radio frequency plasma discharge polymerization (RFPD) of the microtiterplates of polystyrene. The monomers we used were diaminocyclohexane, hexamethylenedisiloxane, and acrylic acid. Other surfaces investigated were: unmodified polystyrene, oxidized polystyrene, hydrophilic silicon oxide, and methylized silicon oxide. Two substances, Tween and bovine serum albumin (BSA), for the prevention of unintended adsorption of ELISA conjugate were also tested and the BSA method was found to be superior for this kind of investigation. Human blood plasma at different dilutions was incubated in the surface-modified microtiterplates followed by incubation of rabbit antibodies against fibrinogen (FG), fibronectin (FN), human serum albumin (HSA), complement factor 3 (C3), and immunoglobulin G (IgG). Visualization of bound antibodies was then made by standard ELISA procedure. At low blood plasma concentrations (plasma dil 1/1000), anti-IgG and anti-HSA were detected at high levels at the majority of surfaces. At high blood plasma concentration (plasma dil 1/10), anti-FG dominated at most surfaces. ELISA activity of FN and C3 were low at most of the surfaces at both plasma concentrations. An 'optimum' plasma dilution for the detection of surface bound FG (the Vroman effect) was not found with the use of the ELISA on any of the surfaces except for the silicon oxide surface. This is in contrast to findings by others who had used isotope-labelled fibrinogen diluted in plasma. However, 'false' Vroman effects occurred if nonionic surfactant was used for the prevention of unspecific binding in the ELISA. PMID- 7873510 TI - Modulating the phase transition temperature and thermosensitivity in N isopropylacrylamide copolymer gels. AB - Temperature-responsive copolymer (or ternary copolymer) gels of N isopropylacrylamide (IPAAm) were synthesized with hydrophobic alkyl methacrylate (RMA), hydrophilic acrylamide (AAm), N,N'-dimethylacrylamide (DMAAm), and N acryloylpyrrolidine (APy) as comonomers. The effects of these comonomers on the phase transition temperature (LCST) and the thermosensitivity have been discussed. The LCST of poly(IPAAm) gel in phosphate buffered saline (PBS) was lowered by the introduction of hydrophobic RMA, and the change in equilibrium swelling ratio with temperature change became smaller with an increase in RMA content. However, a stable skin layer to achieve complete 'on-off' regulation of drug release was formed at a higher temperature by RMA due to hydrophobic interaction of alkyl chains. The LCST of poly(IPAAm-co-AAm) gel increased with an increase in AAm content. However, the thermosensitivity of the gel became smaller. It was suggested that hydrophilic AAm prevented the formation of a dense skin layer at a higher temperature. It was difficult to obtain a complete 'off' state due to an insufficiently dense skin layer in order to stop the drug release. The LCST was raised and great thermosensitivity was possible by the introduction of DMAAm or APy. Poly(IPAAm-co-DMAAm) enabled 'on-off' drug release in response to smaller temperature changes around the body temperature. The molecular design to control transition temperature and thermosensitivity of gel was established. PMID- 7873511 TI - Adsorption of proteins out of plasma onto glass from a separated flow. AB - Perturbations in the adsorption of plasma proteins caused by flow separation were studied quantitatively. An instrument was constructed that causes flow to separate over approximately half the width of a standard microscope slide and the pattern of protein deposition in and near the separated flow was observed by staining the slide with black iron oxide. The slide was mounted at the edge of a Couette flow field established between two concentric cylinders, the outer of which was rotating. The slide was located on the stationary, inner cylinder just downstream of a rectangular bar that causes the flow to separate. After exposure to dilute plasma injected upstream of the bar, the slide was removed and stained with oxide suspension. The resulting, visible pattern was scanned through a video camera and analyzed to yield relative values of stain density that could be quantified. The oxide patterns suggest that proteins were deposited onto the slide less rapidly in and just downstream of the separated flow region than farther downstream. At a shear rate of 6.61 s-1, corresponding to a velocity of 1.32 cm s-1 0.2 cm above the point of flow separation, overall amounts of adsorbed proteins increased with exposure time in the range 3-30 min with the exception of a period from 10 to 11 min when all data show a temporary decrease. In calibration experiments, oxide failed to adhere to slides exposed to purified albumin but adhered copiously to slides exposed to purified fibrinogen. These results suggest that the oxide patterns following plasma exposure are attributable primarily to fibrinogen and that the temporary decrease in the separated flow experiments is attributable to the displacement of fibrinogen by a less stainable protein, conjecturally high molecular weight kininogen and factor XII. This study yields quantitative information confirming earlier findings that were less controlled and non-quantitative. It confirms the hypothesis that the sequence of protein deposition from dilute plasma to glass surfaces is delayed in regions of separated flow. PMID- 7873512 TI - Comparison of medical-grade ultrahigh molecular weight polyethylene microstructure by atomic force microscopy and transmission electron microscopy. AB - Atomic force microscopy is used to image the topography of surfaces of bulk medical-grade ultrahigh molecular weight polyethylene (UHMWPE). Comparison with transmission electron microscopy images demonstrates that the AFM can resolve the plate-like stacks of crystalline lamellae characteristic of UHMWPE without aggressive surface treatment. Surface preparation for the AFM must be carried out by cryomicrotomy at extremely low temperatures to prevent smearing of surface features. Chemically-etched surfaces of UHMWPE require substantially less surface preparation for AFM imaging. PMID- 7873513 TI - Cross-linked chitosan microspheres as carriers for prolonged delivery of macromolecular drugs. AB - Bovine serum albumin (BSA) and diphtheria toxoid (DT) were loaded by passive absorption from aqueous solutions into preformed glutaraldehyde cross-linked chitosan microspheres. In vitro release of BSA under sink conditions at 37 degrees C showed that even though there was a large burst effect, there was a more or less steady increase with time thereafter for several days. Coating the BSA-loaded particles with paraffin oil or with a polymer, such as polylactic acid, modulated drug release. After the initial burst from PLA coated particles, the release rate increased with time for nearly 2 months. Preliminary immunogenicity studies on Wistar rats using DT loaded chitosan spheres showed that the antibody titres were fairly constant over a 5-month period, although very low compared to DT given on alum as control. Histological studies of placebo microspheres intramuscularly injected into rats demonstrated their tissue compatibility. Biodegradation was not complete in 6 months demonstrating the potential of cross-linked chitosan spheres as a long-acting drug delivery vehicle. The study demonstrated the possibility of incorporating biological macromolecules which are very sensitive to organic solvents, pH, temperature, ultrasound, etc. by a passive absorption technique to degradable biopolymer matrices thereby preserving their biological integrity. It is also shown that drugs passively absorbed into such matrices by taking advantage of their swelling behaviour need not necessarily be released completely in the initial 'burst' and a sustained release may be possible for macromolecules thus incorporated. PMID- 7873514 TI - Drug delivery systems based on inorganic materials: I. Synthesis and characterization of a zeolite-cyclophosphamide system. AB - Porous material of the CuX zeolite type has been synthesized and used as support for a classic antitumoral drug--cyclophosphamide (CP). The new material obtained represents a physical mixture of the two components. In vivo tests allowed biochemical and anatomopathological evaluation of antitumoral effects determined by oral administration of the CuX zeolite-CP system. Data obtained show that the intensity of the antitumoral effects of the CuX zeolite-CP system is similar as compared to that achieved by CP. A possible advantage of the CuX zeolite-CP system is the continual maintenance in the blood of a CP concentration ranging between 100 and 1,000 ng ml-1 plasma. PMID- 7873515 TI - Attempts to map the structure and degradation characteristics of aliphatic polyesters derived from lactic and glycolic acids. AB - During the past 5 years, important advances have been accomplished in the understanding of the fate of aliphatic polyesters derived from lactic acid (LA) and glycolic acid (GA) in aqueous media. Hydrolysis of solid LA/GA polymers is now regarded as dependent upon a diffusion-reaction mechanism. Faster central degradation, degradation-induced composition, and morphology changes are three of the most important findings which appeared to be composition-dependent as deduced from the behavior of different LA/GA polymers. An attempt is made to generalize these findings to the whole family and to elaborate a map which could be used to predict degradation characteristics of LA/GA polymers from their initial composition and morphology. PMID- 7873516 TI - The incorporation and release of glucose oxidase and interleukin 2 from a bead formed macroporous hydrophilic polymer matrix. AB - Freeze-thaw photopolymerization at low temperature of a mixed solution of 2 hydroxyethyl methacrylate (HEMA), ethylene glycol dimethacrylate (EDM), and either glucose oxidase (GOx) or interleukin 2 (IL-2) around frozen ice crystals has been used to generate a bead-formed macroporous hydrophilic matrix with potential for immobilization and sustained release. The mean equilibrium acetate buffer content (EBC) of unloaded p-HEMA beads at room temperature and controlled humidity was approximately 72%. The incorporation of GOx into beads significantly increased the EBC to approximately 76%. The release of GOx was characterized by a short initial burst release which declined rapidly until by day 14 no further biologically active enzyme release could be detected. Bead size had no significant effect on the total mean cumulative release of GOx at room temperature. Since only approximately 4% of the original therapeutic load of GOx was released over 14 days a substantial proportion of biologically active enzyme had become associated with the hydrogel matrix surface generating a bead formed immobilised enzyme system. Total cumulative release profiles for IL-2 were almost linear and maintained for at least 16 days. In absolute terms, the proportion of the original theoretical incorporated load subsequently released over this period was low. However, such a low level sustained release of IL-2 may lend itself therapeutically to a reduction in unwanted non-specific systemic activity. PMID- 7873517 TI - Immobilization of carbohydrases on epoxide-, isocyanate-, acid chloride-, and carboxylic acid-activated plastic supports. AB - Methods for the covalent immobilization of alpha-amylase and glucoamylase on to epoxide-, isocyanate-, acid chloride-, and carboxylic acid-activated plastic supports have been optimized. The effects of the following parameters have been examined: coupling time, pH, and temperature; availability of the free essential reacting groups on the supports; porosity of the supports; and enzyme loading. Properties of the immobilized enzymes, such as coupled activity and operational stability were assessed. PMID- 7873518 TI - Hydrogen exchange of the glycyl radical of pyruvate formate-lyase is catalyzed by cysteine 419. AB - Pyruvate formate-lyase (PFL) catalyzes the reversible conversion of CoA and pyruvate into acetyl-CoA and formate. Active enzyme contains a glycyl radical whose alpha-hydrogen undergoes rapid exchange with solvent (t1/2 approximately 5 min at 0 degree C). We have investigated this exchange using site-directed mutagenesis and mechanism-based inactivation. Mutation of the active-site cysteine 419 into a serine, which renders the enzyme catalytically inactive, abolishes alpha-hydrogen exchange in the radical. This suggests that the exchange process is not an intrinsic property of the glycyl radical but is a consequence of its interaction with cysteine 419. This residue is also demonstrated to be involved in the transfer of the radical to acetylphosphinate, a mechanism-based inactivator of the enzyme. In contrast, mutation of the other essential cysteine 418 to a serine has no effect on the hydrogen exchange or the transfer of the radical to acetylphosphinate. A mechanism for the hydrogen exchange catalyzed by cysteine 419 consistent with a redox role for this residue in the normal catalytic reaction is proposed. PMID- 7873519 TI - Two-dimensional affinity resolution electrophoresis demonstrates that three distinct heparin populations interact with antithrombin III. AB - Heparin is a polydisperse, highly sulfated polysaccharide consisting of repeating 1-->4 linked uronic acid and glucosamine sugar residues that binds to coagulation proteins, complement proteins, and growth factors to regulate a variety of biological activities. Heparin is best known as an anticoagulant, an activity that results largely from a specific pentasaccharide sequence in heparin that interacts with a unique site in antithrombin III. Little is known about additional structures within heparin that might interact with antithrombin III or the heparin structures that interact with the myriad of other heparin-binding proteins and peptides. Unfractionated glycosaminoglycan heparin that had been prepared from porcine intestinal mucosa was examined for its capacity to bind antithrombin III using a new technique developed to quantitate that interaction. Two-dimensional affinity resolution electrophoresis is a powerful method that allows assessment of unique species of heparin molecules that bind to protein, allowing determination of heparin molecular weight for each protein-binding heparin species as well as the dissociation constant of each interaction. This study provides the first definitive evidence that glycosaminoglycan heparin contains at least three populations of molecules with affinity for antithrombin III. Furthermore, the affinity of each heparin species for antithrombin III appears to vary inversely with the size of the heparin chain, with some smaller oligosaccharides having greater affinity for antithrombin III than larger oligosaccharides. PMID- 7873520 TI - Human type-alpha transforming growth factor undergoes slow conformational exchange between multiple backbone conformations as characterized by nitrogen-15 relaxation measurements. AB - Human type-alpha transforming growth factor (hTGF alpha) is a small mitogenic protein containing 50 amino acids and three disulfide bonds. It has both sequence and structural homology with epidermal growth factor (EGF). While the three dimensional structures of hTGF alpha and other EGF-like proteins have been studied extensively, relatively little is known about conformational dynamics of these molecules. In this paper we describe nuclear relaxation measurements which probe the molecular dynamics of hTGF alpha in aqueous solution at neutral pH. In order to characterize conformational dynamics of hTGF alpha on both the fast (i.e., sub-nanosecond) and intermediate nitrogen-15 chemical-exchange (i.e., microsecond) time scales, we measured nitrogen-15 relaxation parameters at pH 7.1 +/- 0.1 and a temperature of 30 +/- 0.5 degrees C. Measurements of nitrogen-15 longitudinal (R1) and transverse (R2) relaxation rates, and 1H-15N heteronuclear NOE effects, were then interpreted using an extended Lipari-Szabo analysis [Lipari, G., & Szabo, A. (1982) J. Am. Chem. Soc. 104, 4546-4559; Clore, G. M., Szabo, A., Bax, A., Kay, L. E., Driscoll, P. C., & Gronenborn, A. M. (1990) J. Am. Chem. Soc. 112, 4989-4991] to provide estimates of the locations and amplitudes of fast internal motions and the locations of nitrogen-15 chemical exchange line broadening. These results demonstrate that, under conditions of pH and temperature at which it is tightly bound by the EGF receptor, hTGF alpha is a highly dynamic molecule. Indeed, some 40% of the backbone amide groups of hTGF alpha, including many at the interface between the two subdomains, exhibit significant nitrogen-15 chemical-exchange line broadening indicative of interconversions between multiple protein conformations on the microsecond time scale. The distribution of these sites on the three-dimensional protein structure suggests that these dynamic fluctuations are due to (i) partial unfolding of the core beta-sheet, (ii) hinge-bending motions between the N- and C-terminal subdomains, and/or (iii) disulfide bond isomerization in the solution structure of hTGF alpha at neutral pH. PMID- 7873521 TI - Binding of calcium to individual gamma-carboxyglutamic acid residues of human protein C. AB - Selectively labeled polypeptides comprising the gamma-carboxyglutamic acid (Gla) domain (GD) and helical stack (HS) regions of human protein C (PC), and consisting of amino acid residues 1-47, have been chemically synthesized and their Ca2+ binding properties assessed by [13C]-NMR methods. A total of nine such polypeptides have been studied, each containing one of the Gla residues fully enriched with [13C] at its two gamma-carboxylate carbon atoms. Additions of Ca2+ resulted in readily measurable [13C] chemical shifts, titrations of which were used to obtain apparent dissociation constants for each Gla residue in the presence of all other such residues. The Ca2+ titration data obtained on each of the nine polypeptides showed that Gla residues 6, 16, 25, and 26 were involved in the higher affinity Ca2+ binding sites, whereas the remaining Gla residues, viz., 7, 14, 19, 20, and 29, coordinated Ca2+ more weakly. The results are consistent with conclusions drawn from functional studies obtained with site-directed mutations of individual Gla residues and with the structural model of the GD/HS of human PC. In these cases, Gla residues 6, 16, and 26 served as coordination loci for internally located Ca2+ ions, and GD-related Ca(2+)- and PL-dependent properties of PC and activated PC were dependent on the integrity of these Gla residues. PMID- 7873522 TI - Human lysosomal beta-galactosidase-cathepsin A complex: definition of the beta galactosidase-binding interface on cathepsin A. AB - Human lysosomal beta-galactosidase is organized as a 680-kDa complex with cathepsin A (also named carboxypeptidase L and protective protein), which is necessary to protect beta-galactosidase from intralysosomal proteolysis. To understand the molecular mechanism of beta-galactosidase protection by cathepsin A, we defined the structural organization of their complex including the beta galactosidase-binding interface on cathepsin A. Radiation inactivation analysis suggested the existence of a 168-kDa structural subunit of the complex containing both beta-galactosidase and cathepsin A. Chemical cross-linking of the complex confirmed the existence of this subunit and showed that it is composed of one cathepsin A dimer and one beta-galactosidase monomer. The modeling of the cathepsin A dimer tertiary structure based on atomic coordinates of a wheat carboxypeptidase suggested a putative beta-galactosidase-binding cavity formed by the association of two cathepsin A monomers. According to this model two exposed loops of cathepsin A bordering the cavity were chosen as part of a putative beta galactosidase-binding interface. Synthetic peptides corresponding to these loops were found both to dissociate the complex and to inhibit its in vitro reconstitution from purified cathepsin A and beta-galactosidase. The defined location of the GAL monomer in the complex with 35% of its surface covered by the CathA dimer may explain the stabilizing effect of CathA on GAL in lysosome. PMID- 7873523 TI - Phosphorylation modulates catalytic function and regulation in the cAMP-dependent protein kinase. AB - Site-directed mutagenesis was used to remove a critical phosphorylation site, Thr 197, near the active site of the catalytic subunit of cAMP-dependent protein kinase. This residue is present in a number of protein kinases, and its phosphorylation largely influences catalytic activity. We changed Thr-197 to aspartic acid and alanine and measured the effects of these substitutions on the kinetic mechanism and inhibitor affinities. The mutants were expressed as the free catalytic subunit and as soluble fusion proteins of glutathione-S transferase. The values for KATP and Kpeptide for all three mutants are raised by approximately 2 orders of magnitude relative to the wild-type enzyme. Viscosometric measurements indicate that elevations in Kpeptide are the result of reduced rates for phosphoryl transfer and not reduced substrate affinities. This implies that the loop that contains the phosphothreonine, the activation loop, does not reduce access to the substrate site as proposed for the inactive forms of cdk2 kinase [DeBont, H. L., et al. (1993) Nature 363, 595-602] and MAP kinase [Zhang, F., et al. (1994) Nature 367, 704-711]. The mutants associate slowly with the wild-type regulatory subunit, although the cAMP-free wild-type regulatory subunit inhibits the mutants stoichiometrically. A mutant regulatory subunit that binds cAMP poorly and rapidly inhibits the wild-type catalytic subunit does not inhibit the mutant proteins. These data suggest that the phosphothreonine region serves as a docking surface for the regulatory subunit in the holoenzyme complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873524 TI - Overexpression, purification, and characterization of VanX, a D-, D-dipeptidase which is essential for vancomycin resistance in Enterococcus faecium BM4147. AB - Vancomycin resistance in Enterococcus faecium requires five genes: vanR, vanS, vanH, vanA, and vanX. The functions and mechanism of four gene products have been known, with VanR/S for signal transduction and transcriptional regulation and VanH/A to synthesize D-Ala-D-lactate. But the function of the fifth gene product, VanX, has been unknown until very recently, when Reynolds and colleagues discovered D-, D-dipeptidase activity in crude extracts of a VanX overproducer [Reynolds, P. E., et al. (1994) Mol. Microbiol. 13, 1065-1070]. We report here the expression of VanX in Escherichia coli and its purification to homogeneity. VanX has been characterized as a metal-activated D-, D-dipeptidase with an optimal pH range of 7-9. The kcat and Km of D-Ala-D-Ala in the absence of divalent metal are determined to be 4.7 s-1 and 1 mM, respectively. However, in the presence of metal cations, kcat can be as high as 788 s-1. VanX is unable to hydrolyze D-Ala-D-lactate, the substituted moiety in the peptidoglycan that leads to vancomycin resistance, not only because of low binding affinity (Ki estimated at 242 mM) but also due to a kcat less than 0.005 s-1. The more than 10(5)-fold differential in catalytic efficiency of VanX for hydrolysis of D-Ala-D-Ala vs D Ala-D-lactate leaves D-Ala-D-lactate intact for subsequent incorporation into peptidoglycan.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873525 TI - UDP-N-acetylmuramyl-L-alanine functions as an activator in the regulation of the Escherichia coli glutamate racemase activity. AB - D-Glutamate is an essential component of the bacterial peptidoglycan. In Escherichia coli, the biosynthesis of D-glutamate is catalyzed by a glutamate racemase (encoded by the dga gene) and is regulated by UDP-N-acetylmuramyl-L alanine [Doublet et al. (1994) Biochemistry 33, 5285], a bacterial peptidoglycan subunit precursor. Investigation was conducted to elucidate the interaction between the enzyme and its regulator. Whole and N-terminal truncated enzymes, encoded by individual constructs containing either a full-length or an N-terminal truncated dga gene, were evaluated. In the absence of the regulator, the purified whole enzyme showed a low-level basal racemase activity for which a Km value of 18.9 mM and a Vmax of 0.4 mumol/(min.mg) were determined, using D-glutamate as the substrate. Using the same substrate, in the presence of 6.5 microM UDP-N acetylmuramyl-L-alanine, a Km value of 4.2 mM and a Vmax of 34 mumol/(min.mg) were measured. Similar kinetic parameters for the activated enzyme were obtained using L-glutamate as the substrate. The N-terminal truncated E. coli enzyme, with a 21 amino acid region removed, is similar in size to the Pediococcus pentosaceus glutamate racemase. Effects of the regulator on the full-length and the N terminal truncated enzyme in the dialyzed cell lysate were compared. A host cell line, E. coli WM335 delta recA, containing a nonfunctional chromosomal dga gene was used to minimize the background interference. With 6.5 microM regulator added, the N-terminal truncated enzyme displayed a loss of more than 80% of the activity compared to the full-length enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873526 TI - Trichodiene synthase. Substrate specificity and inhibition. AB - The substrate specificity of the sesquiterpene synthase trichodiene synthase was examined by determining the Vmax and Km parameters for the natural substrate, trans,trans-farnesyl diphosphate (1), its stereoisomer, cis,trans-farnesyl diphosphate, and the tertiary allylic isomer, (3R)-nerolidyl diphosphate (3), using both the native fungal and recombinant enzymes. A series of farnesyl diphosphate analogs, 15, 16, 20, 7, 8, and 9, was also tested as inhibitors of trichodiene synthase. 10-Fluorofarnesyl diphosphate (15) was the most effective competitive inhibitor, with a K1 of 16 nM compared to the Km for 1 of 87 nM, while the ether analog of farnesyl diphosphate, 8, an extremely potent inhibitor of squalene synthase, showed only modest inhibition of trichodiene synthase, with a K1/Km of 70. PMID- 7873527 TI - Trichodiene synthase. Identification of active site residues by site-directed mutagenesis. AB - Derivatization of 5,5'-dithiobis(2-nitrobenzoic acid)-treated trichodiene synthase with [methyl-14C]methyl methanethiosulfonate and analysis of the derived tryptic peptides suggested the presence of two cysteine residues at the active site. The corresponding C146A and C190A mutants were constructed by site-directed mutagenesis. The C190A mutant displayed partial but significantly reduced activity, with a reduction in kcat/Km of 3000 compared to the wild-type trichodiene synthase, while the C146A mutant was essentially inactive. A hybrid trichodiene synthase, constructed from amino acids 1-309 of the Fusarium sporotrichioides enzyme and amino acids 310-383 of the Gibberella pulicaris cyclase, had steady state kinetic parameters nearly identical to those of the wild-type F. sporotrichioides enzyme. From this parent hybrid, a series of mutants was constructed by site-directed mutagenesis in which the amino acids in the base-rich region, 302-306 (DRRYR), were systematically modified. Three of these mutants were overexpressed and purified to homogeneity. The importance of Arg304 for catalysis was established by the observation that the R304K mutant showed a more than 25-fold increase in Km, as well as a 200-fold reduction in kcat. In addition, analysis of the incubation products of the R304K mutant by gas chromatography-mass spectrometry (GC-MS) indicated that farnesyl diphosphate was converted not only to trichodiene but to at least two additional C15H24 hydrocarbons, mle 204. Replacement of the Tyr305 residue of trichodiene synthase with Phe had little effect on kcat, while increasing the Km by a factor of ca. 7 8.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873528 TI - Purification and properties of a Golgi-derived (alpha 1,2)-mannosidase-I from baculovirus-infected lepidopteran insect cells (IPLB-SF21AE) with preferential activity toward mannose6-N-acetylglucosamine2. AB - Because the availability and subcellular distribution of processing mannosidases in cells play such powerful roles in determining ultimate structures of glycoconjugates, we desired to identify, characterize, and investigate possible regulation of mannosidases in infected and noninfected lepidopteran insect cells. Since our previous observations that a mannosidase activity that converted Man6GlcNAc2 to Man5GlcNAc2 was enhanced in virus-infected cells, thus providing the necessary intermediate for further processing to complex-type oligosaccharides, we attempted purification of this enzyme. A mannosidase was isolated and purified from membranes, operationally defined as Golgi, of recombinant baculovirus-infected Spodoptera frugiperda (IPLB-SF-21AE) cells. The molecular mass of this protein was approximately 63 kDa. Assays performed by measuring the conversion of NaB3H4-reduced Man6GlcNAc2-ol to Man5GlcNAc [3H]GlcNAc2-ol demonstrated that the mannosidase activity was dependent on the presence of divalent cations, which was optimal for Ca2+ at pH 6.0. Inclusion of 1-deoxymannojirimycin resulted in 50% inhibition at a concentration of 20 microM, whereas swainsonine did not show such inhibition. No activity was observed with p nitrophenyl alpha-D-mannoside (4 mM) as a substrate. The preferred reduced oligosaccharide substrate was Man6GlcNAc2-ol, with lower activities obtained with Man9GlcNAc2-ol, Man8GlcNAc2-ol, and Man7GlcNAc2-ol. With Man6GlcNAc2-ol as substrate, products smaller than reduced Man5GlcNAc2-ol were not observed. Mannose was also liberated from the glycoprotein, ovalbumin. These properties are consistent with an enzyme classification as a type I (alpha 1,2)-Man6 mannosidase. PMID- 7873529 TI - Interaction of histidine-proline-rich glycoprotein with plasminogen: effect of ligands, pH, ionic strength, and chemical modification. AB - The association of plasma histidine-proline-rich glycoprotein (HPRG) with plasminogen (PLG) was examined using a sucrose density gradient assay in order to evaluate the effects of several relevant conditions on complex formation. Addition of PLG shifts the S-value of 125I-labeled HPRG from 4.8S to 6.8S, providing the first direct evidence that HPRG associates with the zymogen form of plasmin in solution. Complex formation is not sensitive to pH in the range of pH 6.5-8.5, but is abolished at high ionic strength (1 M NaCl). No species differences were found, as either rabbit or human HPRG bound readily to rabbit or human PLG. Of the ligands of HPRG tested, mesoheme (20 microM) but not heparin (M(r) 10,000, 10 microM) inhibits the formation of the HPRG-PLG complex. Modification of lysine residues of HPRG or competitive binding by lysine and anti fibrinolytic agents containing primary amino groups also inhibits association. Conversely, modification of arginine or histidine residues of HPRG has no effect on complex formation. These results indicate that HPRG has independent binding sites for heparin and PLG and confirm that one or more lysine residues of HPRG are involved in its recognition by PLG. The protein-protein interaction was also quantitatively characterized at thermodynamic equilibrium by analytical ultracentrifugation. The stoichiometry and dissociation constant (KD) of the complex were determined from the equilibrium distribution of fluorescein isothiocyanate-labeled PLG in the presence of HPRG. The experimental data were analyzed by nonlinear least-squares curve fitting and indicated that a heterodimer is formed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873530 TI - Acyclic guanosine analogs inhibit DNA polymerases alpha, delta, and epsilon with very different potencies and have unique mechanisms of action. AB - Acyclovir triphosphate, ganciclovir triphosphate and penciclovir triphosphate inhibited DNA polymerases alpha, delta, and epsilon. Each triphosphate preferentially inhibited pol delta, although ganciclovir triphosphate was the most impressive of the three; the Ki for inhibition of pol delta was 2 microM (competitive with dGTP), while the Kis for inhibition of pol alpha and epsilon were 80 and 140 microM, respectively. Each of the compounds was polymerized by pol alpha, delta, and epsilon. Incorporation of acyclovir triphosphate resulted in immediate chain termination, whereas incorporation of ganciclovir triphosphate often allowed polymerization of additional dNTPs. Interestingly, chain termination most often occurred after polymerization of just one additional dNTP onto the ganciclovir monophosphate. All three compounds were very weak inhibitors of DNA primase. Acyclovir triphosphate, however, was a unique inhibitor of the pol alpha-catalyzed elongation of primase-synthesized primers. Immediately after DNA primase synthesized a primer, pol alpha frequently incorporated acyclovir triphosphate with consequent chain termination. If, however, pol alpha did not immediately polymerize acyclovir triphosphate onto the primase-synthesized primer, further dNTPs were readily added and acyclovir triphosphate was incorporated much less frequently. PMID- 7873531 TI - Cooperative binding of estrogen receptor to DNA depends on spacing of binding sites, flanking sequence, and ligand. AB - It has been suggested that cooperative binding of estrogen receptor (ER) may, in part, be responsible for the synergistic activation of transcription of estrogen responsive genes that contain multiple estrogen-response elements (EREs). Experiments described here show that estradiol-liganded ER (E2-ER) binds cooperatively to stereoaligned EREs that are surrounded by naturally occurring flanking sequences, such as an AT-rich region. In contrast, EREs lacking these sequences do not bind E2-ER cooperatively, regardless of ERE spacing or stereoalignment. Moreover, binding is of lower affinity and capacity in the absence of these critical flanking sequences. By varying the sequence of nucleotides adjacent to the ERE, features important for the flanking sequence effect were characterized. Interestingly, when ER was liganded with 4 hydroxytamoxifen (4-OHT), the active metabolite of the widely used therapeutic antiestrogen tamoxifen, the antiestrogen-liganded ER complex (4-OHT-ER) did not bind cooperatively to multiple EREs, regardless of spacing or flanking sequence. We postulate that ERE flanking sequences bestow upon E2-ER enhanced ERE binding capacity and cooperativity, but do not affect 4-OHT-ER-ERE binding. PMID- 7873532 TI - Existence of a transcription factor for the human HMG2 gene positively related to the level of HMG2 mRNA in the cells. AB - A functional gene encoding high mobility group 2 (HMG2) protein, which is an abundant eukaryotic DNA-binding protein, has been isolated. The expression of the HMG2 gene is enhanced in exponentially growing cells and in cells transformed with various viral genes and oncogenes. We attempted to identify and characterize the HMG2 gene structure and transcription factor(s) participating in the expression of the gene. Chloramphenicol acetyltransferase assays to characterize the 5'-flanking region of the human HMG2 gene revealed that the nucleotide sequences in two regions are necessary for expression of the HMG2 gene: one (-85 to +44 region) as a core promoter, and the other (-621 to -493 region) as a cis regulatory element(s). Electrophoresis mobility shift assay with a DNA fragment containing the cis regulatory element and a crude nuclear extract from HeLa cells gave several complexes. Chemical footprint and competition assays indicated that the component giving one of the major complexes recognizes a nucleotide sequence of -499 to -486 in the cis regulatory element. Chloramphenicol acetyltransferase assay indicated that the component giving the major complex is required for the effective transcription of the HMG2 gene. The binding component named HMG2TF (HMG2 transcription factor) contained a protein in apparent molecular size of 85,000, as determined by a UV cross-linking experiment. The amount of HMG2TF in the growing cells and transformed cells increased in positive relationship to the level of expression of HMG2 mRNA in the cells. These results suggest that HMG2 gene expression may be regulated by the relative amount of this transcription factor. PMID- 7873533 TI - Endonuclease III interactions with DNA substrates. 1. Binding and footprinting studies with oligonucleotides containing a reduced apyrimidinic site. AB - The binding of endonuclease III from Escherichia coli to damaged DNA has been studied using gel shift and footprinting assays. Oligonucleotides containing a reduced apyrimidinic (AP) site were used since reduction of the AP site blocks the beta-elimination reaction catalyzed by the enzyme and yields a noncleavable substrate. The Kobs for a 13-mer carrying a centrally located reduced AP site is (2 x 10(6)-(2 x 10(7) M-1, while the Kobs for a 13-mer with no damage is (4.5 x 10(3)-(3.2 x 10(4) M-1 (approximately a 500-fold difference). Larger oligonucleotides would not enter a gel when endonuclease III was bound so that binding constants to oligonucleotides longer than 13 base pairs could not be determined directly. Competition assays suggest that the Kobs measured for both damaged and undamaged 13-mers is a minimum value and that the Kobs for larger oligonucleotides could be an order of magnitude greater. Fluorescence quenching on related 19-mers yielded a specific binding constant for the 19-mer carrying a centrally located reduced AP site for 4 x 10(7) M-1 and a nonspecific binding constant to an undamaged 19-mer of approximately 10(5) M-1 [Xing, D., Dorr, R., Cunningham, R. P., & Scholes, C. P. (1995) Biochemistry 34, 2537-2544]. Several footprinting reagents were used to determine the size and location of the endonuclease III binding site on damaged oligonucleotides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873534 TI - Endonuclease III interactions with DNA substrates. 2. The DNA repair enzyme endonuclease III binds differently to intact DNA and to apyrimidinic/apurinic DNA substrates as shown by tryptophan fluorescence quenching. AB - We have measured the fluorescence of the DNA repair enzyme endonuclease III to discover perturbation to its tryptophans by undamaged DNA and AP (apyrimidinic or apurinic) DNA and to estimate binding affinity for intact and AP DNAs. Endonuclease III has two tryptophans, Trp132 in a helix-hairpin-helix region of possible flexibility near the active site for AP lyase activity and Trp178 in the domain containing the iron-sulfur center of endonuclease III; Trp132 is the more solvent-accessible tryptophan [Kuo, C.-F., McRee, D. E., Fisher, C. L., O'Handley, S. F., & Cunningham, R. P. (1992) Science 258, 434-440]. The fluorescence emission peak wavelength near 350 nm (excitation at 290 nm) indicated an exposure of the fluorescing tryptophans to a polar environment. Quenching of tryptophan fluorescence by iodide demonstrated that there are indeed two tryptophans which are differently accessible to anionic quencher. Significant (approximately 60%) fluorescence quenching occurred when endonuclease III was titrated with high molecular weight duplex undamaged poly(dAdT). The apparent second-order nonspecific binding constant to poly(dAdT) was 4 x 10(7) M-1, and there were approximately 12 base pairs per endonuclease III binding site for binding to poly(dAdT). This nonspecific binding to duplex DNA had ionic character, and there was no fluorescence quenching brought on by single-stranded DNA. A comparison between fluorescence quenching titrations of high molecular weight duplex DNA and undamaged duplex 19-mer oligonucleotide showed that the binding constant to the high molecular weight DNA was approximately 400-fold larger than to the undamaged 19-mer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873535 TI - Expression of bovine heart fructose 6-phosphate,2-kinase:fructose 2,6 bisphosphatase and determination of the role of the carboxyl terminus by mutagenesis. AB - Bovine heart fructose 6-P,2-kinase:fructose 2,6-bisphosphatase was expressed in Escherichia coli. In order to determine the role of the carboxyl-terminal peptide, 49 and 78 amino acids from the C-terminus were deleted using oligonucleotide-directed mutagenesis. The expressed wild-type and mutant enzymes were purified to homogeneity, and the steady-state kinetics of the mutant enzymes were compared to those of the wild-type enzyme. Deletion of 49 residues (Del 49) resulted in a 35% decrease in KmFru6P, a 36% increase in Vmax, and a 2-fold increase in Kcat/Km of the kinase. There was no change in the kinetic properties of the phosphatase activity. Deletion of 78 residues (Del 78) resulted in a 4.5 fold decrease in KmFru6P, a 2.5-fold increase in Vmax, a 12-fold increase in kcat/Km of the kinase, and a 3-fold increase in kcat/Km of the phosphatase. Phosphorylation of the wild-type and Del 49 enzymes resulted in decreased KmFru6P and activation of the kinase without affecting the phosphatase activity. Thermal inactivation rates of the wild-type and Del 49 enzymes were similar, but the rate of Del 78 was more rapid. The phosphorylated wild-type and Del 49 enzymes were more sensitive to thermal inactivation than the dephospho forms. Urea inactivation of the kinase and phosphatase of wild-type and Del 49 were similar, but Del 78 was more sensitive to urea. All phosphorylated enzymes were more susceptible to urea inactivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873536 TI - Role of glycine 212 in the allosteric behavior of phosphofructokinase from Bacillus stearothermophilus. AB - Crystallographic studies indicate that the loop between alpha-helix 8 and beta strand H (the 8H loop) which borders the effector site of Bacillus stearothermophilus phosphofructokinase (BsPFK) is involved in the allosteric mechanism of the enzyme [Schirmer, T., and Evans, P.R. (1990) Nature 343, 140 145]. The residue at one end of this loop, glycine 212, has been proposed to be a pivot about which the loop hinges. Using site-directed mutagenesis, glycine 212 was replaced with valine (G212V). Steady-state kinetic analysis and ligand binding studies on the altered and native PFKs showed that the G212V substitution resulted in discernible changes at the effector site. The mutated PFK required a 3-fold higher concentration of the allosteric inhibitor phosphoenolpyruvate than did the native enzyme to cause the same level of inhibition. The altered PFK had a 2-fold higher dissociation constant for the allosteric activator GDP than the wild-type enzyme. More importantly, whereas the native PFK was fully activated by 1 mM GDP from its PEP-inhibited T-state, the altered enzyme was only marginally activated. On the other hand, the G212V mutation resulted in no changes at the catalytic site of BsPFK. The catalytic rate constant kcat remained unchanged. The altered PFK had the same Km values for ATP and fructose-6-phosphate (Fru-6-P) as did the wild-type enzyme. Furthermore, starting from the same PEP-inhibited T state, both enzymes gave identical sigmoidal responses to increasing Fru-6-P concentration, indicating that Fru-6-P can activate both to the R-state. PMID- 7873537 TI - Helical stability of de novo designed alpha-aminoisobutyric acid-rich peptides at high temperatures. AB - 1D and 2D NMR spectroscopy is used to determine the helical stability of two Aib rich peptides, iBoc-(Aib)3-DkNap-Leu-Aib-Ala-(Aib)2-NH(CH2)2OCH3 (Dk4[7/9]) and Ac-(Aib)2-beta-(1'-naphthyl)Ala-(Aib)2-Phe-(Aib)2-NHMe (Nap3Phe6[6/8]), where the bracket notation indicates the number of Aib-class residues/total number of residues. 2D ROESY experiments, carried out previously on Nap3Phe6[6/8] in DMSO (Basu & Kuki, 1993), showed that this compound adopts the 3(10)-helical conformation at 20 degrees C. The first step in the present work is to apply this technique to the peptide Dk4[7/9], demonstrating that it likewise adopts the 3(10)-helical conformation in chloroform at 20 degrees C. The amide proton shifts of Nap3-Phe6[6/8] in DMSO and Dk4[7/9] in C2D2Cl4 were then monitored by means of 1D NMR over a large temperature range, up to 150 and 120 degrees C, respectively. The nonamer Dk4[7/9] exhibits no evidence of any conformational or unfolding transition as the temperature is raised. The nearly temperature independent amide proton chemical shifts of this nonamer are an indication of retention of the intrahelical hydrogen bonding, which was then verified directly by solvent perturbation with DMSO at 120 degrees C. The resulting hydrogen-bonding pattern confirms that Dk4[7/9] retains its 3(10)-helical conformation in C2D2Cl4 over the entire temperature range. This conformational quietness is exploited to examine the intrinsic temperature dependence of free versus intrahelically hydrogen bonded amide proton shifts within the same peptide structure. It is also shown that Nap3Phe6[6/8] retains its 3(10)-helical conformation over the entire temperature range in the stronger hydrogen-bonding solvent DMSO. The extreme thermal stability of these octameric and nonameric Aib-rich peptides in both solvents is contrasted with that of much longer alanine-rich peptides in water. PMID- 7873538 TI - Kinetic isotope effects on substrate association: reactions of phosphoenolpyruvate with phosphoenolpyruvate carboxylase and pyruvate kinase. AB - Kinetic isotope effects on association have been measured using the remote label methodology developed by O'Leary and Marlier (1979). The isotope effect on V/KA for the first substrate in an obligatorily ordered mechanism is an isotope effect on its second-order rate constant for association with the enzyme. With phosphoenolpyruvate carboxylase the 18(V/KPEP) when the bridging O is labeled decreases from 1.0056 +/- 0.0007 to 0.9943 +/- 0.0002 as the concentration of bicarbonate, the second substrate, increases from 2 to 200 mM. With pyruvate kinase the 18(V/KPEP) decreases from 1.0024 +/- 0.0014 to 0.9928 +/- 0.0027 as the concentration of ADP increases from 1.5 to 30 mM. These inverse kinetic isotope effects are best understood as arising from an isotope effect on the rate constant for forming the Michaelis complex of enzyme and substrate. The inverse value suggests that the bridging oxygen is in a vibrationally stiffer environment in the transition state for the association reaction. PMID- 7873539 TI - Electron tunneling in substrate-reduced trimethylamine dehydrogenase: kinetics of electron transfer and analysis of the tunneling pathway. AB - The reoxidation of substrate-reduced trimethylamine dehydrogenase by the artificial electron acceptor ferricenium hexafluorophosphate was studied by stopped-flow spectroscopy. The rate constants for the two sequential one-electron transfers from the reduced 4Fe-4S center to ferricenium ions were measured, the first (ka = 49 s-1) being about 7 times greater than the second (kb = 7.3 s-1) at 20 degrees C and neutral pH. The temperature dependence of the second electron transfer was studied over the range 10-40 degrees C, and the rate constant ranged from 5.7 to 19.2 s-1. Analysis of the temperature perturbation of kb by Marcus theory yielded values for the reorganizational energy of 1.95 eV and the electronic coupling matrix element of 0.26 cm-1. An electron tunneling pathway distance of 13 +/- 0.7 A was calculated which correlates with the shortest pathway measured from the 4Fe-4S center to the protein surface using the crystallographic coordinates of trimethylamine dehydrogenase. Tyr-442 is implicated in facilitating electron transfer from the enzyme to ferricenium ions. The data suggest a location for the docking site on the surface of trimethylamine dehydrogenase for the physiological electron acceptor (ETF). PMID- 7873540 TI - Investigation of the active site cysteine residue of rat liver mitochondrial aldehyde dehydrogenase by site-directed mutagenesis. AB - To determine the active site cysteine residue in aldehyde dehydrogenase, we mutated amino acid residues 49, 162, and 302 of recombinantly expressed rat liver mitochondrial (class 2) aldehyde dehydrogenase. The C49A and C162A mutants were fully active tetrameric enzymes, although the C162A mutant was found to be highly unstable. The C302A mutant was also a tetramer and bound coenzyme, but lacked both dehydrogenase and esterase activities. To test for the role of cysteine 302 as a nucleophile, the residue was mutated to a serine, a poor nucleophile. this C302S mutant was active but was a much poorer catalyst, with a kcat/Km value 7 x 10(5) times lower than that of the recombinant native enzyme. Unlike with native enzyme where deacylation is rate limiting, formation of the serine hemiacetal intermediate appeared to be the rate-limiting step. Cysteine 302 is the only strictly conserved cysteine residue among all the available sequences of the aldehyde dehydrogenase superfamily, supporting the role of this residue as the active site nucleophile of aldehyde dehydrogenase. PMID- 7873541 TI - Stable secretion of a soluble, oligomeric form of rabies virus glycoprotein: influence of N-glycan processing on secretion. AB - Rabies virus glycoprotein (RGP) is a 505 amino acid type I transmembrane glycoprotein that is important in the pathogenesis of rabies virus infection. RGP also stimulates the development of neutralizing antibodies by the host. N-linked glycosylation is required for both cell surface expression and immunogenicity of RGP. In the current study, a soluble form of RGP, constructed by insertion of a stop codon external to the transmembrane domain, was expressed in transfected Chinese hamster ovary cells. The soluble form of RGP was found to be appropriately antigenic and immunogenic. Similar to full-length RGP, the soluble form was assembled into homodimers and homotrimers. Core glycosylation was required for secretion of soluble RGP and cell surface expression of full-length RGP. In addition, initial glucose trimming of the N-glycans was necessary and sufficient for secretion of soluble RGP and cell surface expression of full length RGP. Further N-glycan processing was not required for secretion or cell surface expression of soluble or full-length RGP, respectively. PMID- 7873542 TI - Determination of v-Mos-catalyzed phosphorylation sites and autophosphorylation sites on MAP kinase kinase by ESI/MS. AB - MAP kinase kinase (MAPKK), a key component of the MAP kinase cascade, is activated through phosphorylation by several protein kinases, including the oncogene v-Mos and its cellular counterpart, c-Mos. The v-Mos-catalyzed phosphorylation sites on recombinant MAPKK1 were identified by electrospray ionization mass spectrometry as S218 and S222, located within a sequence that aligns with the T loop structure of cAMP-dependent protein kinase; these are the same as the Raf-1 phosphorylation site identified previously [Alessi, D. R., et al. (1994) EMBO J. 13, 1610-1619]. Phosphorylation of these sites was kinetically ordered, with S222 preferred over S218. Intramolecular autophosphorylation of these sites was kinetically ordered, with S222 preferred over S218. Intramolecular autophosphorylation of MAPKK occurred at several residues and was increased upon the stimulation of MAPKK activity by v-Mos. Major autophosphorylation sites were residues S298 and Y300. Minor autophosphorylation sites included T23, S299, S218, and either S24 or S25. Sequence similarities were noted between MAPKK autophosphorylation sites and exogenous phosphorylation sites on MAP kinase. Phosphorylation of either S218 or S222 was sufficient for partial MAPKK activation by Mos, and phosphorylation of S222 alone was sufficient for autophosphorylation at S298 and Y300. Mass spectral analysis was also performed on MAPKK1 purified from rabbit skeletal muscle. The peptide containing S218 and S222 was observed in only a singly phosphorylated form, and the peptide containing S298, S299, and Y300 was observed in multiply phosphorylated forms, suggesting that MAPKK is only partially phosphorylated within the T loop but significantly modified in the autophosphorylation loop under physiological conditions. PMID- 7873543 TI - The 2-oxoglutarate/malate translocator of chloroplast envelope membranes: molecular cloning of a transporter containing a 12-helix motif and expression of the functional protein in yeast cells. AB - The 2-oxoglutarate/malate translocator of spinach chloroplasts transports carbon skeletons into chloroplasts for net glutamate synthesis. A sequence of a endoprotease Lys-C peptide derived from the purified protein allowed the design of an oligonucleotide which was then used for a hybridization screening of a cDNA library. A 1945 bp insert of 1 of the isolated clones codes for the entire 569 amino acid residues of the precursor protein corresponding to a molecular mass of 60,288 Da. There was no significant homology to the mitochondrial 2 oxoglutarate/malate carrier from bovine heart or to any other known protein. The translocator protein is composed of a hydrophilic N-terminal region (the transit peptide) with a length of about 90-100 amino acid residues which shows, in contrast to presequences of other known envelope membrane proteins, typical features of higher plant chloroplast transit sequences. The mature protein contains 12 putative transmembrane segments in alpha-helical conformation. It is suggested that this translocator, in contrast to other known transporters of organellar origin which are all homodimers with a 6 + 6 helix folding pattern, may function as a monomer. The in vitro synthesized precursor protein is directed to chloroplasts where it is inserted into the chloroplast envelope membrane in a protease-resistant manner. The cDNA coding for the precursor protein was cloned into the yeast expression vector pEVP11, and this construct was used to transform cells from the fission yeast Schizosaccharomyces pombe. The 2-oxoglutarate/malate translocator could be functionally expressed in the transformed yeast cells, and the recombinant protein showed substrate specificities identical to those of the authentic chloroplast protein. PMID- 7873544 TI - Specialized chromatin structure domain boundary elements flanking a Drosophila heat shock gene locus are under torsional strain in vivo. AB - An in vivo assay employing psoralen cross-linking was used to investigate the presence of unrestrained supercoiling in DNA sequences located in nontranscribed regions flanking the 3' ends of the pair of divergent heat shock protein 70 (hsp70) genes at locus 87A7 of Drosophila. Two of the regions examined contain sequences comprising the previously defined specialized chromatin structure elements (scs and scs'). Both of these putative chromosomal domain boundaries exhibited very similar levels of unrestrained negative supercoiling that remained high regardless of the transcriptional status of the hsp70 genes. The steric accessibility of the scs region before heat shock was 3-fold higher than either flanking region (consistent with its previously documented DNase I hypersensitivity); this increased an additional 2-fold following hsp70 gene activation without a concomitant rise in the accessibility of flanking regions. Most notably, a sequence which lies outside the presumed 87A7 domain, as defined by the centromere-proximal scs element, exhibited no detectable torsional tension regardless of gene activity in the domain. A sequence located just inside the scs region displayed a low level of tension that was also essentially unaffected by transcription, consistent with data obtained previously for a similarly situated fragment at the centromere-distal scs' location. The existence of a highly localized region of supercoiling within the scs and scs' sequences might be related to their activity in vivo as insulators of chromosomal position effects in Drosophila. PMID- 7873545 TI - Myoglobin-NO at low pH: free four-coordinated heme in the protein pocket. AB - In either sperm whale or horse heart myoglobin, binding of NO and lowering of solution pH work together to weaken, and ultimately break, the bond between iron and the proximal histidine. This is reminiscent of the reaction observed at neutral pH in the case of guanylate cyclase, the heme enzyme that catalyzes the conversion of GTP to cGMP. Bond breaking is characterized by a spectral change from a nine-line to a three-line ESR signal and accompanied by a shift from 420 to 387 nm in the UV-vis spectrum of the Soret band maximum. Analysis of the pH dependent spectral changes shows that they are reversible, at least within a few hours, that the transition is cooperative, involving six protons during pH lowering but only two as it is raised, and that the pK is about 4.7. Different proteins exhibit different pK values, which are generally lower than that for "chelated" protoheme. The pK differences reflect the extra bond stability afforded by the protein structure. Investigations of thermal and photochemical NO displacement by CO suggest that the local pocket around the ligand, although significantly altered (according to circular dichroism investigations), nonetheless still imposes a barrier against the outward diffusion of ligand into the solvent. Nanosecond and picosecond flash photolysis shows that in proteins at low pH there is an extremely efficient geminate recombination of the ligand with the four-coordinated species through a single-exponential process. This occurs to a significantly larger extent than for the case of NO-"chelated" protoheme (where no distal barrier for ligand is present). At neutral pH, when the proximal histidine bond is intact, the geminate recombination for NO takes longer and displays multiexponential kinetics. Altogether, these results suggest that, even though distal effects probably also play a role, proximal effects make an important contribution in modulating ligand-iron bond formation. PMID- 7873546 TI - Mapping the heparin-binding site of mucus proteinase inhibitor. AB - Heparin accelerates the inhibition of neutrophil elastase by mucus proteinase inhibitor (MPI), the physiological antielastase of airways as a result of its binding with the inhibitor [Faller, B., Mely, Y., Gerard, D., & Bieth, J. G. (1992) Biochemistry 31, 8285-8290]. To explore the heparin-binding site of the inhibitor, we have modified the lysine and arginine residues of MPI and its isolated C-terminal domain by using 4-N,N-(dimethylamino)azobenzene-4' isothiocyano-2'-sulfonic acid (S-DABITC) [Chang, J. Y. (1989) J. Biol. Chem. 264, 3111-3115] and (p-hydroxyphenyl)glyoxal (HPG) (Yamasaki, R. B., Vega, A., & Feeney, R. E. (1980) Anal. Biochem. 109, 32-40], respectively. The derivatizations were done in the absence and presence of a 4.5 kDa heparin fraction with a low degree of polydispersity. The effect of chemical modification of the inhibitors on their affinity for heparin was tested using two complementary procedures, one based on the ability of heparin to accelerate the inhibition of chymotrypsin by the inhibitors and the other exploiting the affinity of the inhibitors for immobilized heparin. Modification of a limited number of lysine and arginine residues in full-length MPI led to a 6-fold decrease in affinity for heparin. The presence of the polymer during the modification reactions significantly prevented this effect. Amino acid sequencing unambiguously identified the heparin-protected lysines as Lys 13 and Lys 87, located on the N-terminal and C-terminal domains of MPI, respectively. Heparin apparently protects mainly two arginine residues from modification by HPG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873547 TI - Differential dependence on chromatin structure for copper and iron ion induction of DNA double-strand breaks. AB - The induction of DNA DSB (double-strand breaks) in isolated nuclear chromatin by Cu(II) or Fe(II)-EDTA in the presence of H2O2 and ascorbate has been compared to DSB induction by gamma-radiation. V79 nuclei embedded in agarose plugs were treated with each agent on ice, and the resultant DNA fragments were analyzed by pulsed-field gel electrophoresis. In the absence of low molecular weight radical scavengers, both irradiation and treatment with iron ion induced random DSB, as judged by the size distribution of DNA fragments, and the yield of DSB in each case was enhanced by either the expansion of chromatin (approximately 5-fold) or the removal of histones (21-25-fold) before treatment. In contrast, treatment with Cu(II) produced small DNA fragments of uniform size (approximately 100-200 kbp), independent of the yield of DSB. In addition, neither the DNA fragment size nor the yield of DSB produced by Cu(II) was affected by the prior removal of histones from chromatin. Deproteinized DNA was degraded randomly by Cu(II) but at a slower rate than observed for chromatin. In the presence of ascorbate, H2O2 was found to be essential for DSB induction by Fe(II)-EDTA but not by Cu(II), possibly because H2O2 can be produced from ascorbate and Cu(II) in the presence of oxygen. Despite the above differences between the production of DSB by the two metal ions, DSB induction in native chromatin by either metal ion was blocked by 0.1 M EDTA or 0.25 M thiourea but was resistant to the hydroxyl radical scavengers 0.25 M DMSO and 0.25 M mannitol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873548 TI - Binding of 2,7-diaminomitosene to DNA: model for the precovalent recognition of DNA by activated mitomycin C. AB - Mitomycin C (MC), mitomycin A, porfiromycin, BMY-25067, and BMY-25287, antitumor antibiotics collectively termed "mitosanes", were found to have no appreciable binding affinity to various natural and synthetic DNAs, as tested by UV spectrophotometry and equilibrium dialysis. Further tests of DNA binding applied to MC including thermal melting measurements, displacement of ethidium fluorescence, and unwinding of closed circular DNA were similarly negative. In contrast, 2,7-diaminomitosene (2,7-DAM), a major end product of the reductive activation of MC, binds to the same series of DNAs by all of these criteria. In the presence of DNA its UV absorbance at the 313 nm maximum decreased and underwent a slight red shift. This effect was used for determining DNA binding constants (Kb) by the spectrophotometric titration method. At pH 6.0 the Kbs of three natural DNAs with varying GC content, as well as poly(dA-dT).poly(dA-dT), and poly(dG-dC).poly(dG-dC), were all in the range of (1.2-5.3) x 10(4) (M nucleotide)-1, with no apparent specificity of binding. Poly(dG-m5dC).poly(dG m5dC) displayed a slightly higher Kb ((7.5-8.4) x 10(4)). Binding of other, closely related mitosenes was tested to calf thymus DNA by equilibrium dialysis. Neither the presence of a 1-OH substituent, removal of the 10-carbamoyl group, nor methylation of the 2-amino group modifies the binding affinity of the mitosenes significantly. The 1-phosphate substituent abolishes binding. The binding of 2,7-DAM to DNA increased with decreasing pH and decreasing ionic strength. It was determined that 2,7-DAM is protonated at the 2-amino group with a pKa = 7.55, and this correlated well with the observed pH dependence of the binding, indicating that the binding affinity has a strong electrostatic component. This was confirmed by the finding that the extrapolated Kb to 1 M Na+ concentration diminishes to only 10% of the value of Kb at 0.01 M Na+ concentration. Viscosity tests showed conclusively that 2,7-DAM intercalates in DNA, in a nonspecific manner. DNA binding by 2,7-DAM is shown to be a close model of the binding of the reduced activated form of MC, previously characterized indirectly [Teng, S. P., Woodson, S. A., and Crothers, D. M. (1989) Biochemistry 28, 3901-3907]. The nonspecific precovalent binding of the active form may serve in the cell to concentrate the drug at its critical target, DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873549 TI - Cold denaturation of an icosahedral virus. The role of entropy in virus assembly. AB - Assembly of icosahedral viruses is not completely understood at the molecular level. The main puzzle is to answer how chemically identical protein subunits take up unique positionally dependent conformations during the process of assembly. The stability of the ribonucleoprotein particles of cowpea mosaic virus (CPMV) to pressures and subzero temperatures has been studied. At room temperature, reversible pressure denaturation of CPMV is obtained only in the presence of 5.0 M urea. On the other hand, when the temperature is decreased to 15 degrees C, the ribonucleoprotein components denature, at 2.5 kbar, in the presence of 1.0 M urea. At temperatures close to -20 degrees C, denaturation is obtained even in the absence of urea. Whereas the denaturation promoted by pressure and urea at room temperature is reversible, virus particles denatured when the temperature is decreased under pressure cannot reassemble. Bis-ANS binding data suggest that this irreversibility may be related to protein release from RNA, which probably does not occur under denaturating conditions at room temperature. The contributions of enthalpy (delta H*) and entropy (delta S*) for the free energy of association of CPMV are calculated from the cold denaturation curves under pressure. The entropy change is positive and large, making the assembly of ribonucleoprotein components an entropy-driven process, suggesting that the burial of nonpolar side chains during the process of assembly is the structural foundation for CPMV assembly. PMID- 7873550 TI - 8-Azido-ATP modification of cytochrome c: retardation of its electron-transfer activity to cytochrome c oxidase. AB - Horse heart cytochrome c has been modified by 8-azido-ATP and the electron transfer activity of the modified cytochrome c's to bovine heart cytochrome c oxidase (CcO) under physiological ionic strengths has been studied by the laser flash photolysis technique with 5-deazariboflavin and EDTA as the electron donor. The intermolecular electron transfer between the redox protein partners was shown to be extremely slow. The 8-azido-ATP-modified system exhibited less than 5% of the intracomplex electron-transfer rate observed between native cytochrome c and CcO under otherwise identical conditions. The binding affinity of the modified cytochrome c was greatly reduced (3 orders of magnitude) at low ionic strengths; however, it was only slightly reduced (by a factor of 2) relative to the native protein at physiological ionic strengths. Thus, the binding affinity of the ATP cytochrome c adducts is relatively insensitive to the ionic strength compared to the native enzyme, suggesting that a different docking conformation is assumed by the ATP-cytochrome c adducts in their interaction with the oxidase. Since the redox potential of the modified cytochrome c is close to the value of its native form, we conclude that there has been a change in the docking of the cytochrome c to CcO and the electronic coupling between heme c and CuA upon 8-azido-ATP modification. PMID- 7873551 TI - Studies of 8-azido-ATP adducts reveal two mechanisms by which ATP binding to cytochrome c could inhibit respiration. AB - We have proposed that the binding of ATP at a site of substantial affinity and specificity could regulate the activity of cytochrome c with its physiological partners and thus the overall efficiency of mitochondrial electron transport. We now describe the use of ATP affinity-labeled protein to test the effect of occupancy of that site, which includes the invariant arginine 91, on the activity of cytochrome c with purified cytochrome c reductase and oxidase and its association with the mitochondrial inner membrane. Electron-transfer activities with the reductase and oxidase were inhibited by site occupancy to 41% and 11-15% of native values, respectively. The marked difference in the degree of inhibition of activity that distinguishes the reactions with the two major physiological partners was sufficient to cause, in whole mitochondria, a demonstrable shift from a situation in which there is a rate-limiting transfer from the reductase to cytochrome c, to a state where rates are more evenly matched for transfers between cytochrome c and the two redox partners. Site occupancy also substantially reduces the ionic strength necessary for half-maximal dissociation of cytochrome c from the membrane. These data imply that the decreased efficiency of electron transfer caused by ATP attachment can be attributed to a decrease in the protein's activity with individual physiological partners, possibly compounded with a decrease in its affinity for the inner mitochondrial membrane, and suggest that feedback regulation by ATP of cellular respiration operates in like manner. PMID- 7873552 TI - Role of charged amino acid pairs in subdomain-1 of actin in interactions with myosin. AB - Yeast actin mutants with alanines replacing charged amino acid pairs D24/D25, E99/E100, D80/D81, and E83/K84 were studied to assess their role in interactions with myosin. In a previous report Dictyostelium actin filaments with residues D24/D25 or E99/E100 replaced with histidines showed complete or partial loss of filament sliding in the in vitro motility assay [Johara, M., et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 2127-2131]. In the motility experiments reported here, actin filaments with alanines substituted at D24/D25 or E99/E100 moved in the presence of 0.7% methylcellulose at velocities similar to those of wild-type yeast actin. Without methylcellulose, mutant filaments dissociated from the assay surface upon addition of ATP with little or no sliding detected. In contrast to this, filaments with alanines substituted at D80/D81 or E83/K84 were motile in the presence and absence of methylcellulose. Direct binding measurements involving cosedimentation of D24A/D25A and E99A/E100A actins with myosin subfragment-1 (S-1) in the presence of ATP revealed 3- and 2-fold decreases in their binding constants, respectively, compared to wild-type actin. In the absence of ATP all yeast actins had a similar affinity for S-1. A large decrease in the activation of S-1 ATPase was observed for both D24A/D25A and E99A/E100A actins. The D80A/D81A and E83A/K84A actin filaments showed normal S-1 binding and activation of ATPase activity. These results demonstrate the involvement of the D24/D25 and E99/E100 charged residues in the weak binding of myosin to actin and reveal that D80/D81 and E83/K84 residues in the 79-92 helix do not modulate actomyosin interactions. PMID- 7873553 TI - Effect of expression of human spermidine/spermine N1-acetyltransferase in Escherichia coli. AB - A plasmid expression vector, pINSAT2, was constructed in order to express spermidine/spermine N1-acetyltransferase (SSAT) in Escherichia coli. Cells transfected with this vector produced large amounts of SSAT, amounting to up to 2% of the soluble protein when isopropyl beta-D-thiogalactopyranoside (IPTG) was added and 0.3% of the soluble protein in the absence of inducer. The growth rate of cells expressing SSAT was reduced, and all of the cellular spermidine was converted to N1-acetylspermidine, much of which was excreted. Putrescine and 1 methylspermidine, which is not a substrate for SSAT, could reverse the effects of SSAT expression on growth, but spermidine was only effective when the amount of SSAT expression was limited by omitting the IPTG inducer. The lack of stimulation of growth by spermidine correlated with its complete conversion to N1 acetylspermidine. These results show that N1-acetylspermine is not able to substitute for the unmodified polyamines in supporting growth and suggest that acetylation is a physiological response to convert excess polyamines to a physiologically inert form which is readily excreted. Cells expressing large amounts of SSAT were much more sensitive to the growth inhibitory action of the antitumor agent N1,N12-bis(ethyl)spermine, supporting the hypothesis that the ability of such bis(ethyl) polyamines to induce SSAT contributes to their antiproliferative actions. SSAT was readily purified to homogeneity from extracts of DH5 alpha cells containing pINSAT2. The purified enzyme had a similar specific activity and Km values for spermine and spermidine as the enzyme purified from human colon cancer cells, suggesting that posttranslational modifications specific to eukaryotes are not needed for enzymatic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873554 TI - Isomorphous crystal structures of Escherichia coli dihydrofolate reductase complexed with folate, 5-deazafolate, and 5,10-dideazatetrahydrofolate: mechanistic implications. AB - Crystal structures of Escherichia coli dihydrofolate reductase (ecDHFR, EC 1.5.1.3) in binary complexes with folate, 5-deazafolate (5dfol), and 5,10 dideazatetrahydrofolate (ddTHF) have been refined to R-factors of 13.7%, 14.9%, and 14.5%, respectively, all at 1.9 A. All three are isomorphous with a previously reported binary complex of ecDHFR with methotrexate (MTX), in space group P6(1), two molecules per asymmetric unit [Bolin, J. T., Filman, D. J., Matthews, D. A., Hamlin, R. C., & Kraut, J. (1982) J. Biol. Chem. 257, 13650 13662]. A hitherto unobserved water molecule is hydrogen bonded to the pteridine N5 and O4 in both molecules of the asymmetric unit of the folate complex (but not the 5dfol or ddTHF complexes), supporting the hypothesis that N5 protonation of bound substrate, an important step of the DHFR reaction, occurs by way of such a water molecule. There is no indication of a hydrogen bond between N8 of 5dfol and the backbone carbonyl of Ile-5, suggesting that the bacterial enzyme, unlike the human enzyme [Davies, J. F., II, Delcamp, T. J., Prendergast, N. J., Ashford, V. A., Freisheim, J. H., & Kraut, J. (1990) Biochemistry 29, 9467-9479], does not favor protonation at N8. Perhaps this explains why bacterial DHFR is much less effective than vertebrate DHFR in folate reduction. When the ecDHFR.NADPH complex (space group P3221; M. R. Sawaya, in preparation) is superimposed on the folate and 5dfol complexes, the distances from pteridine C6 to nicotinamide C4 were found to be 2.9 and 2.8 A, respectively, in close agreement with the theoretically calculated optimal distance in the transition state for hydride transfer [Wu, Y. D., & Houk, K. N. (1987) J. Am. Chem. Soc. 109, 906-908, 2226 2227]. In contrast to the planar ring system of folate or 5dfol, the reduced pteridine ring of ddTHF is severely puckered and bent toward the nicotinamide pocket, with the reduced pyridine ring assuming a half-chair type of conformation. This change in shape causes the pteridine ring to bind with O4 closer to Trp-22(N epsilon 1) by over 0.5 A, so that an invariant water molecule now bridges these two atoms with ideal hydrogen bonds. Furthermore, while the pABA rings of folate and 5dfol are nearly coincident and closer to the alpha C helix than to the alpha B helix, those of MTX and ddTHF are displaced along the binding crevice by approximately 1.1 and 0.6 A, respectively, and are equidistant from alpha B and alpha C.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7873556 TI - Allosteric regulation by calcium of rabbit polyclonal anti-cyclic GMP antibody. AB - Calcium increased the binding of rabbit polyclonal antibodies and cGMP by increasing antibody affinity without altering the number of binding sites (Bmax). Competitive binding studies revealed that calcium increased the affinity of antibody for cGMP derivatives similarly, suggesting that the effects of this cation were antigen-independent. Kinetic binding studies demonstrated that calcium increased affinity by decreasing the dissociation rate without altering the association rate of antigen and antibody. Studies of the dissociation of antigen-antibody complexes preformed in the absence of calcium suggested that this cation regulated antibody function allosterically. These data contrast with those obtained previously suggesting that calcium regulated the interaction of cAMP and antibodies by increasing Bmax without altering affinity by reaction coupling. Re-analysis of those data demonstrated that calcium increased the affinity without altering the number of binding sites of antibodies to cAMP, in close agreement with the present results. These data suggest that allosteric modulation of antibody function by calcium may be a general mechanism regulating the interaction of polyclonal antibodies with cyclic nucleotides. PMID- 7873555 TI - Intestinal fatty acid binding protein: folding of fluorescein-modified proteins. AB - The rat intestinal fatty acid binding protein is an almost all beta-sheet protein that encloses a large interior cavity into which the fatty acid ligand binds. The protein contains neither cysteine nor proline. In a previous report, six site directed mutants were obtained, each having a single cysteine residue [Jiang, N., & Frieden, C., (1993) Biochemistry 32, 11015-11021] either in a turn or pointed into the cavity. In this report, each mutant has been unfolded in denaturant and modified with 5-iodoacetamido-fluorescein to introduce a large, bulky, and fluorescent group into the protein at a known position. In all cases, fluorescence changes indicated that the modified protein refolded, and circular dichroism measurements suggested that the refolded protein appeared to be mostly beta-sheet. Denaturation curves suggest that for two mutants intermediate structures exist at denaturant concentrations well below the midpoint of the unfolding curve. For each modified, folded protein, one- and two-dimensional 1H NMR spectra were accumulated and compared to the unmodified and wild-type proteins. While the spectra for the modified proteins showed a number of changes in chemical shifts, they were also consistent with folded proteins on the basis of the degree of chemical shift dispersion. Of the six modified mutant proteins, two appear to have the fluorescein group located in the cavity, but only one of these did not bind fatty acid. The remaining modified proteins are capable of ligand binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873557 TI - Cross-linking of porin with glutardialdehyde: a test for the adequacy of premises of cross-linking theory. AB - Exposure of porin from Escherichia coli to glutardialdehyde followed by SDS-gel electrophoresis in 3% polyacrylamide yielded three bands that were identified in order of decreasing mobility as monomers and two and three cross-linked polypeptide chains. The distribution of protein among the three species for different extents of reaction showed a remarkably good agreement with corresponding values predicted from cross linking theory for an oligomer composed of three identical subunits arranged according to a 3-fold rotation axis. Electrophoresis performed in 7.5% polyacrylamide yielded four bands that were assigned to polypeptide chain monomers, dimers, and two types of trimers carrying two and three intersubunit cross-links. Our findings provide evidence that the central premise of cross-linking theory, viz. that the intersubunit cross-links formed upon exposure of a protein to a bifunctional reagent be governed by the symmetry of the molecule, is valid. Careful interpretation of cross-linking experiments thus proves an effective method to assess the oligomeric structure of a protein and reveal the symmetry underlying the spatial arrangement of the subunits within the molecule. PMID- 7873558 TI - Characterization of the okra mucilage by interaction with Gal, GalNAc and GlcNAc specific lectins. AB - A bio-active polysaccharide, which was the major component of the extract of the common okra, Hibiscus esculentus, was isolated from the extract by precipitation with ethanol between 28.5 to 45%. According to a previous report (Whistler, R.L. and Conrad, H.E. (1954) J. Am. Chem. Soc. 76, 1673-1674), this polysaccharide contains the Gal alpha 1-->4Gal sequence, which is the ligand for the uropathogenic Escherichia coli and toxic lectins. Analysis of the binding property of the okra polysaccharide by precipitin assay with Gal, GalNAc and GlcNAc specific lectins showed that this okra mucilage reacted best with Mistletoe toxic lectin-I (ML-I) and precipitated over 80% of the ML-I nitrogen (5.1 micrograms N) added. It also precipitated well with Abrus precatorius (APA), Momordica charantia (MCA) and Ricinus communis (RCA1) agglutinins, but poorly with other lectins. The results obtained suggest that this polysaccharide is a valuable reagent to differentiate Gal specific lectins from the GalNAc and/or GlcNAc specific series. PMID- 7873559 TI - Characterization of muscle glyceraldehyde-3-phosphate dehydrogenase isoforms from euthermic and induced hibernating Jaculus orientalis. AB - The specific activity of D-glyceraldehyde-3-phosphate (G3P) dehydrogenase (phosphorylating) (GPDH, EC 1.2.1.12) found in skeletal muscle of induced hibernating jerboa (Jaculus orientalis) was 3-4-fold lower than in the euthermic animal. The comparative analysis of the soluble protein fraction of these tissues by SDS-PAGE and Western blotting showed a significant decrease in the intensity of a protein band of about 36 kDa, the GPDH subunit, in hibernating jerboa. After using the same purification procedure, the GPDH from muscle of hibernating jerboa exhibited lower values for both apparent optimal temperature and specific activity than the enzyme from the euthermic animal. Non-linear Arrhenius plots were obtained in both cases, but the Ea values calculated for the GPDH from hibernating tissue were higher. Although in both purified enzyme preparations three isoelectric GPDH isoforms, exhibiting pI values in the range 8.2-7.5, were resolved by chromatofocusing, clear differences were observed in these preparations concerning the relative contribution to the total enzymatic activity of the two main isoforms, named GPDH I (pI values, 8.1-8.2) and GPDH II (pI values, 7.8-7.9). Thus, whereas GPDH I was the major isoform purified from euthermic muscle, accounting for more than 90% of the total activity, the amount of activity due to GPDH II reached up to 65% in preparations of hibernating jerboa. All isoforms exhibited similar native and subunit molecular masses and cross-reacted with an anti-GPDH antibody raised against the GPDH I. However, the two muscle GPDH isoforms prevailing under hibernating conditions exhibited a decreased catalytic efficiency when compared with the corresponding major isoforms purified from euthermic animals, as indicated by their different specific activities and kinetic parameters, i.e. relatively high Km and low Vmax values. Since the glycolytic flow has been found to be widely reduced in skeletal muscle of induced hibernating jerboa, the changes in the GPDH isoforms described in the present study could provide a molecular basis to explain some of the metabolic changes associated with mammalian hibernation. PMID- 7873560 TI - Hydroxyl radical generation following ischaemia-reperfusion in cell-free perfused rat kidney. AB - The difficulty in direct detection of oxygen-derived free radicals (OFR) in the intact kidney has left uncertain the role of OFR in renal hypoperfusion injury. Salicylate hydroxylation was used as a sensitive method of estimating the extent of production of highly reactive hydroxyl radicals in renal ischaemia-reperfusion injury in the intact rat kidney perfused with recirculating cell-free medium. The reaction products were detected and quantified by HPLC with electrochemical detection. Hydroxyl radicals were detected as 2,5-dihydroxybenzoic acid (2,5 DHBA). Ischaemia for 15 min followed by reperfusion for 15 min caused more than a twofold increase in 2,5-DHBA concentration (to 2279 +/- 225 pg/g tissue weight) compared to controls (933 +/- 103, P < 0.001). Addition of 15 mM dimethylthiourea (DMTU) before induction of ischaemia prevented this increase. Induction of hypoxia for 15 min with continued perfusion (as a model of low-flow ischaemia) had no significant effect on hydroxyl radical formation. We conclude that significant quantities of hydroxyl radicals form in the absence of circulating leucocytes during reperfusion following ischaemia, but not during hypoxia in the perfused rat kidney. PMID- 7873561 TI - Purification of ginger proteases by DEAE-Sepharose and isoelectric focusing. AB - Ginger proteases in ginger rhizome (Zingiber officinale roscoe) were extracted from the ginger acetone powder and purified on DEAE-Sepharose and Sephadex G-75 columns. Before the purification, excess p-chloromercuribenzoate was added to the enzymes to prevent their autodigestion. The mercuribenzoate-proteases were further purified and fractionated by isoelectric focusing in Ampholine of pH 3-10 or pH 4-6. The proteases were fractionated into three components by the isoelectric focusing, having pI value of 4.5, 4.6 and 4.8 respectively. All these proteases had a molecular mass of 29,000 as measured by SDS-polyacrylamide gel electrophoresis and by TSK G2000SW XL gel chromatography. The Ampholine in the purified enzymes can quickly be removed by the gel chromatography of TSK G2000SW. Some divalent metal ions, such as Hg2+, Cu2+, Cd2+, and Zn2+, strongly inhibited these purified enzymes. PMID- 7873562 TI - Non-uniform spatial distributions of both the magnitude and phase of AC electric fields determine dielectrophoretic forces. AB - It is well known that the conventional dielectrophoretic force acting on a polarised particle in a non-uniform AC electric field is proportional to the in phase component of the induced dipole moment and the non-uniformity of the field strength. In contrast, the travelling-wave-dielectrophoretic force that acts on a particle subjected to a travelling electric field is proportional to the out-of phase component of the induced dipole moment. We derive a theory that unifies the description and interpretation of conventional dielectrophoretic and travelling wave-dielectrophoretic forces. We show that a particle in a non-uniform AC electric field experiences a dielectrophoretic force due to spatial non uniformities of the magnitude and the phase of the field interacting, respectively, with the in-phase and out-of-phase components of the induced dipole moment. The theory is used to explain the translational effects observed for particles in the presence of standing, travelling and rotating fields in several experimental electrode configurations. The good agreement found between the experimental observations and the theoretical predictions validate the theory. PMID- 7873563 TI - An aminopeptidase activity from porcine kidney that hydrolyzes oxytocin and vasopressin: purification and partial characterization. AB - An aminopeptidase from porcine kidney, hydrolyzing oxytocin and vasopressin in vitro, was purified by chromatography on hydroxyapatite, DEAE-cellulose and nickel ion chelate gel and gel filtration on Sephadex G-100. The enzyme appeared to be a high molecular mass (M(r) 105,000) monomeric protein. It was sensitive to inhibition by metal chelator, o-phenanthroline. Cobalt ion and sulfhydryl activator, 2-mercaptoethanol, had activating effects, while p chloromercuribenzoate, amino acids with large hydrophobic side chains, L-cystine and aminopeptidase inhibitors, bestatin and amastatin, had inhibitory effects on the enzyme activity. The enzyme hydrolyzed several aminoacyl p-nitroanilides, and had the highest specificity against S-benzyl-L-cysteine p-nitroanilide. The properties of the enzyme were distinct from those of well-characterized leucyl aminopeptidase (EC 3.4.11.1), membrane alanyl aminopeptidase (EC 3.4.11.2) and primate placental cystinyl aminopeptidase (EC 3.4.11.3). PMID- 7873564 TI - An aminopeptidase P from Lactococcus lactis with original specificity. AB - An aminopeptidase P (E.C. 3.4.11.9) that cleaves the Arg-1-Pro-2 bond of bradykinin has been isolated for the first time from Lactococcus lactis. The peptidase was purified to homogeneity in a 3-step procedure and characterized. It is a monomeric metalloenzyme with a 43 kDa molecular mass, activated by Mn2+ and inhibited by DTT. It differs from the majority of aminopeptidases P already described by displaying a specificity for X-Pro-Pro N-terminal and probably an extended binding site that could accommodate amino acid residues beyond the P'2 position of the substrate. PMID- 7873565 TI - Regulation of valine catabolism in canine tissues: tissue distributions of branched-chain aminotransferase and 2-oxo acid dehydrogenase complex, methacrylyl CoA hydratase and 3-hydroxyisobutyryl-CoA hydrolase. AB - To clarify the valine catabolism, the activities of principal enzymes in its catabolic pathway, branched-chain aminotransferase, branched-chain 2-oxo acid dehydrogenase complex, methacrylyl-CoA hydratase and 3-hydroxyisobutyryl-CoA hydrolase, were measured using canine tissues. After killing of beagle dogs, tissues (liver, pancreas, kidney, heart, skeletal muscle and mucosae of digestive organs such as stomach, small intestine and colon) were removed and immediately frozen. Branched-chain aminotransferase activity in liver was the lowest among the tissues measured. In contrast, the activities of branched-chain 2-oxo acid dehydrogenase complex in liver as well as in kidney were relatively high and the enzyme complex activities were markedly low in small intestine and skeletal muscle. The activities of methacrylyl-CoA hydratase and 3-hydroxyisobutyryl-CoA hydrolase were relatively high in all tissues, suggesting that a cytotoxic intermediate, methacrylyl-CoA, is immediately degraded to non-toxic compounds, 3 hydroxyisobutyrate and free CoA. These findings suggest that the consumption of branched-chain amino acids in the absorption site (small intestine) is suppressed in order to supply them to the whole body, in particular to skeletal muscle and that skeletal muscle might act as a storage of gluconeogenic amino acids. The high capacity to dispose methacrylyl-CoA produced in the valine catabolism is suggested to play an important role in protecting cells against the toxic effects of methacrylyl-CoA. PMID- 7873566 TI - Electrochemical reduction of the biliverdin-serum albumin complex as monitored by absorption and circular dichroism spectroscopy. AB - The cathodic reduction at the mercury electrode of a biliverdin IX alpha-serum albumin complex at physiological pH in an aqueous buffer containing percentages of DMSO ranging from 4% to 20% is studied by cyclic voltametry and controlled potential coulometry. The progression of pigment disappearance and the (stereochemical) nature of the product are monitored by chromatography, UV visible absorption and circular dichroism spectroscopy. Upon reduction, albumin bound biliverdin IX alpha, with a slight preference for the P-helicity, affords the corresponding bound bilirubin IX alpha -with an M-chirality conformation. The complex is reduced at -0.64 V (vs. SCE; 8% DMSO), only a little shifted compared to reduction of free biliverdin IX alpha under the same conditions. In contrast, an analogous bilirubin IX alpha-serum albumin complex is essentially inert towards cathodic reduction under conditions where free bilirubin IX alpha is reduced, indicating a better shielding by the protein of the bilirubin IX alpha molecule from the electrode surface. The presence of relative position (as in the biliverdins IX alpha and XIII alpha) or absence (as in mesobiliverdin IX alpha) of vinyl groups in the pigment does not have a significant effect upon its electroreduction behaviour, indicating that the process is not sensitive to the subtle differences imposed by vinyl groups upon the structure of the corresponding biliverdin-albumin complexes. PMID- 7873567 TI - Thiol groups in proteins as endogenous reductants to determine glutathione protein mixed disulphides in biological systems. AB - A novel method for glutathione-protein mixed disulphide (GSSP) determination, based on the use of protein sulphydryl groups as endogenous reductant and on the spectrophotometric determination of reduced glutathione, is described. The procedure is based on the observation that acid-precipitated proteins from different rat tissues rapidly release GSH from GSSP when brought to neutral pH. The basal GSSP content determined in rat liver, heart, lung, testis, spleen and brain corresponded to that reported in the literature and determined by more complex sample preparation or labor-intensive analytical procedures. PMID- 7873568 TI - Age-related changes in collagen packing of human articular cartilage. AB - We have used X-ray scattering techniques to determine if the lateral packing of collagen molecules in the fibrils of human articular cartilage changes with age. Such changes would affect the available intrafibrillar volume and consequently the amount of intrafibrillar water. Measurements were made both in the presence and absence of compression on samples from donors aged 20 to 90 years. We find a weak though statistically significant tendency towards less dense collagen packing in native tissue as a function of age. However, the increase in packing density in response to pressure does not change with age, and the packing density in articular cartilage from which the proteoglycan molecules have been removed is similarly not age-dependent. The small increase in intrafibrillar water indicated by our data is insufficient to explain the reported increase in fibril diameter in samples from aged donors. PMID- 7873569 TI - Investigation of the role of reactive oxygen species in bilirubin metabolism in the Gunn rat. AB - It has been previously established that the attenuation of hepatic lipid peroxidation by a fat-free diet is accompanied by a marked rise in plasma bilirubin in Gunn rats. Present in vitro studies confirmed that microsomal lipid peroxidation caused the concurrent degradation of added bilirubin but failed to show that microsomal superoxide, hydroxyl radical or hydrogen peroxide would degrade bilirubin. Moreover, although injection of vitamin E completely inhibited microsomal lipid peroxidation and bilirubin degradation it had no effect on plasma bilirubin. No evidence has therefore been obtained that in Gunn rats, in the absence of bilirubin glucuronidation, that reactive oxygen species provide a significant physiological pathway of bilirubin disposal. PMID- 7873570 TI - Isolation and characterization of a tyrosinase from the skin of the white silky fowl (Gallina lanigera) employing copper saturated diethylaminoethyl-cellulose. AB - Tyrosinase was purified to apparent homogeneity from the skin of the White Silky fowl (Gallina lanigera). Under alkaline conditions copper ions from a complex with the diethylaminoethyl moiety of DEAE-cellulose, allowing the purification of the enzyme in a one step chromatography. In polyacrylamide gel electrophoresis containing sodium dodecyl sulfate the purified tyrosinase displays a single band with a relative molecular mass of 66,000 Da. The crystalline tyrosinase was obtained from 32-33% saturated solution of ammonium sulfate. The enzyme catalyzes the o-hydroxylation of L-tyrosine to L-dihydroxyphenylalanine as well as the oxidation of pyrocatechol to o-benzoquinone. For the pyrocatechol oxidation the Michaelis Menten constant Km, is calculated to be around 1.19 x 10(-3) M. PMID- 7873571 TI - Strain- and sex-specific differences in the glutathione S-transferase class pi in the mouse examined by gradient elution of the glutathione-affinity matrix and reverse-phase high performance liquid chromatography. AB - A gradient elution with glutathione (GSH) from a GSH-Sepharose 6B affinity column separated the hepatic mouse glutathione S-transferases (GST) to the alpha-, mu- and pi-classes. The GST-dependent conjugation of atrazine and glutathione was catalyzed by a pi-class GST. The pi- and mu-classes were both identified by their respective specific substrates, and after reverse-phase HPLC, by N-terminal analysis of 19-35 of the amino acids. The alpha-class GST was associated with a high selenium-independent GSH peroxidase activity and the purified protein had a N-blocked terminal. Strain related differences in the pi-class GST of the CD-1, C57BL/6, DBA/2 and Swiss-Webster males were observed by PhastGel electrophoresis of the GSH affinity chromatograph separated fractions, reverse phase HPLC and by N-terminal amino acid sequence analysis. PMID- 7873572 TI - Specificity of an esterase (XYLD) from Pseudomonas fluorescens subsp. cellulosa. AB - Activity of an esterase from Pseudomonas fluorescens subsp. cellulosa (XYLD) on an insoluble feruloylated hemicellulose substrate (de-starched wheat bran) was dependent on the source of added endo-xylanase. The esterase exhibited high selectivity for the nature, position of linkage and size of the feruloylated oligosaccharides generated by hydrolysis of the hemicellulose. Increased affinity of XYLD with increasing size of the oligosaccharide substrate suggests that optimal activity is observed on substrates with at least 4 sugars. PMID- 7873573 TI - Dietary regulation of sucrase-isomaltase gene expression in rat jejunum. AB - We have previously demonstrated that intake of fat as well as carbohydrate affects the activity and immunoreactive amount of sucrase-isomaltase (S-I) in rat jejunum. To examine whether diet-related changes in sucrase and isomaltase activities are accompanied by the variations of sucrase-isomaltase mRNA levels, 7 week-old rats were fed either a high-long-chain triacylglycerols diet (73 energy% as corn oil), a high-medium-chain triacylglycerols (MCT) diet (66 energy% as MCT, 7 energy% as corn oil) or a high-carbohydrate diet (70 energy% as corn starch) for 7 days. Northern blot analysis revealed that S-I mRNA levels were abundant in the jejunum of rats fed the high-MCT diet; the levels were similar to those in the rats fed the high-carbohydrate diet. Force-feeding a high-sucrose diet (40 energy% as sucrose) brought about a parallel rise in both S-I mRNA and sodium/D glucose cotransporter (SGLT1) mRNA levels within 12 h. Force-feeding the high-MCT diet also produced an elevation of S-I mRNA and SGLT1 mRNA. However, force feeding a diet containing alpha-methylglucoside, a non-metabolizable but actively transported sugar, did not increase S-I mRNA or SGLT1 mRNA level; sucrase activity was nevertheless elevated by feeding alpha-methylglucoside diet. These results suggest that not only carbohydrate intake but also MCT intake might influence S-I mRNA and SGLT1 mRNA levels in the jejunum, presumably through common metabolite(s) of carbohydrates and MCT, and that carbohydrate may play another role in enhancement of the sucrase activity through modulation of translation and/or posttranslational modifications of the sucrase-isomaltase complex. PMID- 7873574 TI - Regulation by physical training of enzyme activity and gene expression of branched-chain 2-oxo acid dehydrogenase complex in rat skeletal muscle. AB - We examined the effects of short-term (5 weeks) and long-term (12 weeks) physical training on actual and total activities, protein content and mRNA abundance of branched-chain 2-oxo acid dehydrogenase complex in rat skeletal muscle. The actual and total activities were significantly increased approximately 60% and approximately 40%, respectively, by long-term training. No effects of short-term training on activities were observed. The increase in the total activity corresponded to increased protein content of the E1 alpha and E2 components of the complex. On the other hand, mRNA abundance for E1 alpha and E2 were not affected by the training, but that for E1 beta was slightly, but significantly increased by both short-term and long-term trainings. These divergent alterations of the message levels for the subunits of the complex suggest that posttranslational regulatory mechanisms determine the amount of the complex in skeletal muscle. Since the complex is located in the mitochondrial matrix space, mitochondrial biogenesis in response to the training was examined by determining the content of mitochondrial DNA in the muscle. The mitochondrial DNA was proportionally increased with the total activity as well as the protein content of the complex, suggesting that expression of branched-chain 2-oxo acid dehydrogenase complex in skeletal muscle in response to physical training is associated with mitochondrial biogenesis. PMID- 7873575 TI - Presence of free D-glutamate and D-aspartate in rat tissues. AB - The presence of free D-glutamate was demonstrated for the first time in rat liver, kidney and brain. This is based on the findings that the D-glutamate as well as D-aspartate in the tissue extracts co-chromatographed exactly with the authentic standards on HPLC, and that the treatment of the extracts with D aspartate oxidase mostly abolished the HPLC peaks of these compounds. Contents of these acidic D-amino acids in the liver and kidney, as well as the percentages of D/(D + L), were lower in female than in male, while D-aspartate oxidase activities in the same tissues were inversely lower in male than in female, in agreement with a probable role of the enzyme. A significant correlation was observed between D-aspartate and D-glutamate contents in the liver, kidney and brain of individual animals, with the D-glutamate contents always higher than the D-aspartate contents. PMID- 7873576 TI - Isoelectric restriction of human immunoglobulin isotypes. AB - The partition of human serum immunoglobulins along a pH gradient of ampholynes was investigated using the recently developed method of preparative isoelectrofocusing. Each isotype was demonstrated to display a specific pI range, with limited overlapping. IgA appear to be the most acidic serum immunoglobulins while IgG are clearly basic. PMID- 7873577 TI - Tyrosinase: a comprehensive review of its mechanism. PMID- 7873578 TI - Secondary structure prediction of beta-subunits of the gonadotropin-thyrotropin family from its aligned sequences using environment-dependent amino-acid substitution tables and conformational propensities. AB - The secondary structures of beta-subunits of the glycoprotein hormone family, LH (luteinizing hormone), CG (chorionic gonadotropin), FSH (follicle stimulating hormone), TSH (thyroid stimulating hormone), and GTH I/GTH II (two types of fish gonadotropins), are predicted by comparing an amino-acid substitution pattern at equivalent sites in their aligned sequences with environment-dependent amino-acid substitution tables and conformational propensities calculated from other protein families whose three-dimensional structures are known. According to the prediction results, together with other structural information obtained from experiments, the following points come up as important structural features of the beta-subunits of this family; The regions assigned to regular secondary structures (one alpha-helix and three beta-strands) are considered to constitute a core of the beta-subunits. They involve interaction sites with carbohydrate and alpha-subunit. Out of the six disulfide bonds formed in the beta-subunit, four are located together on one side of the core, and the other two on the opposite side. The two regions assumed to be a receptor binding region from experiments (therefore, species-specific regions) are predicted as loops located on the same side of the beta-subunit in this study. Some of the predicted loops are rich in proline residues. While the positions of proline residues are conserved in the family generally, there are hormone- or species-specific ones in the loop that is assumed to take part in receptor binding. The possible importance of proline residues in hormone or species specificity is discussed. (After submitting the manuscript the X-ray crystal structure of human CG was published. In order to evaluate the prediction, the original manuscript is kept intact and a comparison has been made between the prediction results and the crystal structure in an appendix). PMID- 7873579 TI - Complementary roles of mutations at positions 69 and 242 in a class A beta lactamase. AB - Analysis of the three-dimensional structure of class A beta-lactamases suggests that deformation of the substrate binding site can be produced by changes in the hydrophobicity of residue 69 behind the beta-sheet and by outward movement of the B3 beta-strand by introduction of a non-glycine residue at position 242 on the B4 beta-strand. By site-directed mutagenesis Met69-IleGly242-Cys, a double mutant, of the OHIO-1 beta-lactamase, was constructed. The minimum inhibitory concentrations (MICs) of the double mutant compared with the wild type and each single mutant revealed an increased susceptibility to beta-lactams. Met69 IleGly242Cys hydrolyzed cephaloridine (Km = 213 microM) but had Km > 500 microM for other beta-lactams tested including cefotaxime, and demonstrated a higher apparent Ki for inhibitors (clavulanate Ki = 500 microM sulbactam = 434 microM, and tazobactam = 70 microM). In a competition experiment with cephaloridine, the apparent Ki values for penicillin and cefotaxime remained low, 21 microM and 0.7 microM, respectively. Since Ile is twice as hydrophobic as Met, the Met69-Ile mutation may result in partial collapse of the oxyanion hole. This would also increase the distance between Arg-244 and the carboxyl of clavulanic acid. The Gly242-Cys mutation opens the lower portion of the active site to bulky R groups of cephalosporins. Although these two mutations result in a catalytically impaired enzyme, they can be used to model the complementary role of two distinct residues, neither of which interacts directly with beta-lactam substrates or inhibitors. PMID- 7873580 TI - Age-related change in redox state of human serum albumin. AB - Human serum albumin (HSA) is the mixture of human mercaptalbumin (HMA, reduced form) and human nonmercaptalbumin (HNA, oxidized form). We developed a rapid and concise HPLC system to obtain the clear resolution of HSA into HMA and HNA, using an Asahipak GS-520H column. The mean value of the fraction of HMA (f(HMA)) for healthy young male subjects was 0.76 +/- 0.04 (n = 54). However, the f(HMA, 60 90) value for healthy elderly subjects (where the numbers in brackets indicate the range of ages) was 0.48 +/- 0.06 (n = 183). In healthy elderly subjects, f(HMA) was significantly lower than in healthy young male subjects, indicating that HSA in the elderly becomes more oxidized than in the young subjects. Consequently, we suggest that one of the important functions of serum albumin could be to participate in the maintenance of a constant redox potential in the extracellular fluids, thus securing a certain redox buffer capacity. f(HMA) on HSA might reflect this redox buffer capacity with age. PMID- 7873581 TI - beta-Lactamase mutations far from the active site influence inhibitor binding. AB - Analysis of the three dimensional structure of the class A beta-lactamases shows that Arg-244, a spatially conserved residue important for inactivation by clavulanic acid, is held in place by a hydrogen (H) bond from the residue at 276. An Asn276-Gly mutant of OHIO-1, an SHV family class A enzyme, was constructed to investigate the importance of that interaction. Compared to a strain expressing the wild type enzyme, OHIO-1, the MIC of the Asn276-Gly mutant strain was more resistant to clavulanate (0.25 vs. 2.0 micrograms/ml) in the presence of ampicillin (16 micrograms/ml) but was as susceptible to sulbactam or tazobactam plus ampicillin as the OHIO-1 bearing strain. No difference in MICs was observed when other beta-lactams were tested. Consistent with the susceptibility test results, the apparent Ki of clavulanate for the Asn276-Gly enzyme (4.5 microM) was 10-fold greater than OHIO-1 (0.4 microM). For sulbactam and tazobactam the apparent Ki decreased for Asn276-Gly enzyme (1.0 and 0.1 micrograms/ml, respectively) compared to the wild-type parent (17 and 0.7 micrograms/ml, respectively). Comparing the Asn276-Gly heta-lactamase with OHIO-1, the Vmax for most substrates except cephaloridine did not change substantially. There was a 2 15 fold decreased affinity (Km) and catalytic efficiency (Vmax/Km) for beta lactam substrates. These data support the observation and emphasize the role for this H bonding residue in orienting Arg-244 towards the active site. PMID- 7873582 TI - Biosynthesis of plasma factor XIII: evidence for transcription and translation in hepatoma cells. AB - Factor XIIIa belongs to a family of ubiquitous transglutaminases, which catalyze formation of covalent bonds between the epsilon-amino group of specific lysines and the gamma-carboxyl group of glutamines. Factor XIII is synthesized as a zymogen and after activation, it participates in both the coagulation and fibrinolytic mechanisms. Most transglutaminases are intracellular, but factor XIII is both intracellular and extracellular. the biosynthesis of extracellular (plasma) factor XIII, with the structure of a noncovalent heterotetramer, A2B2, is complex. Here, evidence is presented from PCR analysis and Northern blotting that mRNAs for both A and B subunits are present in the liver. The distribution of mRNA, specific for factor XIII subunits, in various human tissues was also analyzed. Among the tissues examined, the only signal for B subunit was found in the liver. For subunit A, the signal was observed in placenta, liver, kidney, lung, skeletal muscle and heart with varying intensities; in brain or pancreas there was no signal. With an immunoperoxidase method, factor XIII A subunit was identified in the PLC/PRF/5 cell line. By ELISA and reverse immunoblotting, with antibodies specific for the A-B complex, it was also shown that these cells produce and secrete factor XIII. From all of these results, we conclude that the liver is a source of plasma factor XIII, and that the complex A2B2 is secreted from these cells. PMID- 7873583 TI - Redox equilibria between the regulatory thiols of light/dark-modulated chloroplast enzymes and dithiothreitol: fine-tuning by metabolites. AB - Three light/dark-modulated chloroplast enzymes, namely NADP-dependent malate dehydrogenase (EC 1.1.1.82), D-fructose 1,6-bisphosphatase (EC 3.1.3.11), and phosphoribulokinase (EC 2.7.1.19) were purified to apparent homogeneity from spinach leaves. Equilibrium constants for the covalent modification of the regulatory disulfide bonds of these enzymes in dithiothreitol (DTT)-redox buffer were determined according to a previously published method in the literature (Clancey and Gilbert (1987) J. Biol. Chem. 262, 13545-13549). The thiol/disulfide redox potential (Kox) was defined as the ratio of reduced to oxidized dithiothreitol at which 50% of the maximal enzyme activity was observed after equilibrium had been established. All Kox values were very high, comparable to those of extracellular disulfide containing proteins: 0.23 +/- 0.02 for NADP malate dehydrogenase, 0.59 +/- 0.17 for phosphoribulokinase, and 0.70 +/- 0.16 for D-fructose 1,6-bisphosphatase. The equilibrium constants for the reactions between these enzymes and the redox buffers were also determined in the presence of various concentrations of specific metabolites known to influence the rates of reduction and oxidation. Increasing concentrations of D-fructose 1,6-bisphosphate in the presence of Ca2+ shift the equilibrium constant between D-fructose 1,6 bisphosphatase and the DTT-redox buffer to much lower values. A decreasing NADPH/(NADP + NADPH) ratio increases the Kox of NADP-malate dehydrogenase in the redox buffer to very high values. For PRK, low concentrations of ATP result in a slight decrease of the Kox that is not further affected by higher ATP concentrations. The differences of the equilibrium constants of NADP-malate dehydrogenase and D-fructose 1,6-bisphosphatase as dependent upon the NADPH/(NADP + NADPH) ratio and the concentration of D-fructose 1,6-bisphosphate, respectively, reflect a mechanism of feed-back and feed-forward regulation by the product NADP and the substrate D-fructose 1,6-bisphosphate, respectively. Thus the actual activation state of these two key enzymes of chloroplast metabolism are determined in an independent manner. The relatively small effect of the ATP concentration upon the redox potential of phosphoribulokinase indicates that fine regulation at this step might be achieved on another level (e.g., catalysis or aggregation state). PMID- 7873584 TI - Characterization of distinct alpha- and gamma-type gliadins and low molecular weight components from wheat endosperm as coeliac immunoreactive proteins. AB - Distinct alpha- and gamma-type gliadins, as well as a few low molecular weight components have been identified as coeliac immunoreactive proteins from a chloroform/methanol extract from wheat endosperm. Characterization of these components involved the combination of reverse-phase high-performance liquid chromatography, immunoblotting following SDS-PAGE using a coeliac serum and microsequencing analysis. This has allowed the identification of a group of gliadins with different molecular weights, according to their N-terminal amino acid sequence: five alpha-type gliadins of 31, 35, 38 and two of 45 kDa, one gamma 2-type gliadin of 40 kDa, two gamma 3-type gliadins of 31, and 50 kDa, and two gamma-type gliadins with an atypical gliadin N-terminal of 31, and 40 kDa, as well as a few unidentified low molecular weight components and three N-terminal blocked proteins, all exhibiting similar antigenicity. PMID- 7873585 TI - Investigations of the interactions of saccharides with the lysozyme from bacteriophage lambda. AB - The bacteriophage lambda R gene has been isolated into an Escherichia coli expression system and the R gene product, a lysozyme, has been overexpressed and purified to homogeneity using an efficient purification procedure. A turbidimetric assay utilizing chloroform-treated E. coli cells has been optimized to assess the bacteriolytic activity of the purified enzyme. Using this assay, oligomers of beta (1 --> 4) N-acetyl-D-glucosamine at high concentrations were shown to inhibit lysozyme but were not cleaved by the enzyme. Differential scanning calorimetry revealed that the thermal denaturation of lysozyme was found to increase in the presence of (GlcNAc)3 and (GlcNAc)5. The lysozyme was also expressed in an E. coli strain auxotrophic for methionine, allowing for the incorporation of [methyl-13C]methionine into the enzyme. An alteration of the [1H 13C]HMQC NMR spectra of the labelled enzyme was observed in the presence of (GlcNAc)5. Commercially available nitrophenyl glycosides did not act as substrates for lambda lysozyme. The results indicate that lambda lysozyme has specific interactions with oligosaccharides of N-acetylglucosamine, but is incapable of hydrolyzing these sugars. The relevance of the structure of peptidoglycan to the activity of lambda lysozyme is discussed. PMID- 7873586 TI - The structure and physicochemical properties of rat liver macrophage migration inhibitory factor. AB - We expressed rat macrophage migration inhibitory factor (rMIF) in E. coli using the cDNA isolated from a rat liver cDNA library. rMIF specifically bound glutathione (dissociation constant = 500 microM). We purified rMIF homogeneously on SDS-PAGE by S-hexylglutathione Sepharose affinity column chromatography and Sephadex G-100 column chromatography. The amino-acid sequence of rMIF was highly homologous to that of human MIF from a T-cell line; only a single amino-acid residue was substituted if conservative amino-acid substitutions were involved. The molecular weight of rMIF was calculated to be 12.4 kDa and 23.6 kDa by SDS PAGE and analytical ultracentrifugation, respectively. Thus, it was concluded that the native rMIF formed a homodimeric structure. Proton nuclear magnetic resonance (1H-NMR) study revealed that rMIF was less thermostable (the denaturing temperature was from 50-60 degrees C) than human MIF (the denaturing temperature is about 80 degrees C (Nishihira et al. (1993) Biochem. Mol. Biol. Int. 31, 841 850). The secondary structure of rMIF evaluated by 1H-NMR experiments revealed that the contents of alpha-helix, beta-strand, and coil were 13.8%, 55.6%, and 30.6%, respectively. PMID- 7873587 TI - Hemorrhagic principles in the venom of Bitis arietans, a viperous snake. II. Enzymatic properties with special reference to substrate specificity. AB - The optimal pH of the proteinase activity of hemorrhagins, BHRa and BHRb, isolated from the venom of Bitis arietans (puff adder) is pH 9. The activity was inhibited by metal chelating agents such as EDTA, 1,10-phenanthroline and 8 hydroxyquinoline, but not by phenylmethanesulfonyl fluoride and soybean trypsin inhibitor, suggesting that they are metalloproteinases. The hemorrhagins hydrolyzed all gelatin preparations derived from types I, II, III and IV collagen. On the other hand, only type IV native collagen was hydrolyzed. Gel electrophoretic profiles of type IV collagen hydrolysates suggested that the hemorrhagins affect the collagen helical chains at different cleavage sites. The hemorrhagins hydrolyzed several synthetic peptides such as angiotensin I and luteinizing hormone-releasing hormone, but not synthetic substrates for bacterial and animal collagenases. The hydrolysis of various peptides indicated that the hemorrhagins are endopeptidases. The insulin B chain is cleaved by BHRa and BHRb at 11 and 10 positions, respectively. The substrate specificity of the hemorrhagins was compared with those of known hemorrhagic and nonhemorrhagic venom proteinases. PMID- 7873588 TI - Effect of the tertiary structure alteration by ligation on the interface contacts between subunits of hemoglobin. AB - In order to obtain knowledge of molecular mechanism underlying the cooperative ligand binding to hemoglobin (Hb), atomic contacts between subunits in the hypothetical intermediate quaternary structures have been investigated using the atomic coordinates of O2-liganded subunits' within the T-state. The atomic coordinates are obtained by energy minimization of hypothetical atomic coordinate sets in which an O2 molecule is placed near the iron atom of a deoxy subunit. In an 'O2-liganded beta-subunit', drastic atomic displacements occur at the distal side amino-acid residues E11Val and E12Leu in order to produce sufficient space for the O2 molecule, while this kind of atomic displacement cannot be seen in an 'O2-liganded alpha-subunit'. Therefore the features of structural alterations at heme surroundings by O2 ligation are markedly different between alpha- and beta subunits. When an alpha-subunit in deoxy Hb is replaced by the corresponding 'O2 liganded subunit', tight inter-subunit contacts between alpha 1FG4(92)Arg and the two residues beta 2C3(37)Trp and beta 2C6(40)Arg strengthen greatly, while, when a beta-subunit is replaced by a corresponding O2-liganded one, serious steric hindrances occur between beta 2FG4(97)His and alpha 1CD2(44)Pro. The characteristics of structural alteration confirm that the effect of O2-ligation at alpha-subunit is transmitted to the other subunit through the alpha FG4Arg. However, the role of FG4His in beta-subunit is not as clear as that of the alpha FG4Arg. PMID- 7873589 TI - Acid stabilization of human growth hormone equilibrium folding intermediates. AB - Equilibrium denaturation experiments were performed on human growth hormone (hGH) under acidic conditions (pH 1.5-3.0) and different protein concentrations. At 0.1 mg/ml hGH using intrinsic tryptophan fluorescence and far-UV circular dichroism (CD) detection, midpoint values of 4.6 M GdnHCl were observed that are identical to those obtained at neutral pH. However, the delta G values were reduced at pH 2.5 relative to pH 8.0 (10.5 vs. 15 kcal/mol). Increasing the protein concentration to 1 mg/ml resulted in a biphasic denaturation profile by far-UV CD detection at 222 nm, while near-UV CD measurements at 295 nm yielded a cooperative transition with a midpoint value of 3.6 M GdnHCl. These results indicate that equilibrium intermediates having a propensity to aggregate are highly populated under acid conditions. Static light scattering measurements performed under partial unfolding conditions (4.5 M GdnHCl) at pH 2.5 confirmed the existence of a large molecular weight (congruent to 80 kDa) self-associated intermediate. No evidence of aggregation was found for hGH under acid conditions in the absence of denaturant, indicating that self-association results from the formation of an intermediate. Equilibrium GdnHCl concentration-jump experiments confirmed that association only occurs from an intermediate species and not from any other conformational state, and formation of the self-associated intermediate can lead to irreversible loss of protein due to precipitation. These results demonstrate that acid stabilizes equilibrium folding intermediates of hGH. PMID- 7873590 TI - Regulation of the inducible soybean nitrate reductase isoform in mutants lacking constitutive isoform(s). AB - In soybean, three nitrate reductase isoforms have been identified based on metabolic regulation, substrate specificity, and kinetic parameters. Two isoforms have been termed constitutive, as their activities are present without the addition exogenous nitrate to soybean seedlings. The third activity is termed inducible, as its activity is present only when soybean plants have been supplied with nitrate. The purpose of this study was to examine the regulation of the inducible nitrate reductase isoform in soybean mutants lacking one or both of the constitutive isoforms. Based on evidence obtained through measurements of enzyme activity, Western blotting, and RNA determinations, the absence of one or both of the constitutive nitrate reductase isoforms has no effect on the metabolite regulation of the inducible nitrate reductase isoform. PMID- 7873591 TI - Diminished activity of the first N-glycosylation enzyme, dolichol-P-dependent N acetylglucosamine-1-P transferase (GPT), gives rise to mutant phenotypes in yeast. AB - The enzyme which initiates the dolichol pathway of protein N-glycosylation, dolichol-P-dependent N-acetylglucosamine-1-P transferase (GPT), is encoded by the ALG7 gene. Essential for viability, ALG7 has been evolutionarily conserved and shown to be involved in a variety of functions. ALG7 is an early growth-response gene in yeast, and downregulation of ALG7 expression results in diminished N glycosylation and secretion of Xenopus oocyte proteins. We have now investigated the consequences of diminished GPT activity in yeast using mutant ALG7 genes with deletions in the 3' untranslated region (3' UTR). We show that a 2.5- to 4-fold reduction in GPT activity gave rise to distinct phenotypes, whose severity was inversely related to the level of GPT activity. These phenotypes included hypersensitivity to tunicamycin, enlarged cell size, extensive aggregation, lack of a typical stationary (G0) arrest, and defective spore germination. We conclude that yeast cells are sensitive to GPT dosage, and that attenuation of GPT activity interferes with various functions in the yeast life cycle. PMID- 7873592 TI - Identification of the site of non-enzymatic glycation of glutathione peroxidase: rationalization of the glycation-related catalytic alterations on the basis of three-dimensional protein structure. AB - Bovine erythrocyte glutathione peroxidase has been glycated in vitro by incubation in 0.05 M glucose at pH 7.4. Upon glycation the estimated KM for t butylhydroperoxide reduction increased by approx. 3-fold in comparison to non glycated glutathione peroxidase. The glycated protein fraction was stabilized by NaBH4 reduction and subjected to tryptic cleavage. Affinity chromatography of the tryptic digest on m-aminophenylboronate-Agarose resulted in the isolation of a single glycated peptide. The peptide was identified as T94-K117 by amino-acid composition comparison to the published amino-acid sequence for this enzyme. The glycation site has been identified as the epsilon-NH2 group of K110. Examination of the three-dimensional structure of bovine erythrocyte glutathione peroxidase indicates that K110 lies on the surface of the protein approximately 15 A away from the active site selenocysteine (SEC 45). Modeling studies indicate that K110 can communicate via H-bonded interactions with the alpha-helix containing the active site residues (SEC-45 and R50). The observed elevation of KM upon glycation of bovine glutathione peroxidase is discussed in terms of the disruption of the long range H-bonded interaction. PMID- 7873593 TI - Fluorescence analysis of the interaction between ganglioside GM1-containing phospholipid vesicles and the B subunit of cholera toxin. AB - Binding of cholera toxin B protomer (CT-B) to a pyrene-labeled analogue of its ganglioside GM1 receptor (pyrene-GM1) in the absence and presence of phosphatidylcholine vesicles was monitored using steady-state fluorescence spectroscopy. CT-B association with pyrene-GM1 micelles induces changes in the fluorescence properties of this ganglioside analogue that are consistent with its conversion from an excimer to a monomer form. Incubation of pyrene-GM1 with preformed vesicles of phosphatidylcholine (PC) results in complete conversion of pyrene-GM1 to its monomer form, however, unlike with CT-B binding, incorporation of pyrene-GM1 into PC vesicles occurs with a concomitant loss of fluorescence quenching by the small polar quenching agent acrylamide. Subsequent binding of CT B to the PC-GM1 composite vesicles causes no further change in the pyrene fluorescence emission spectrum but does appear to increase acrylamide accessibility. These data lead to the conclusion that cholera toxin binding to a cell membrane alters membrane packing at the site of attachment. Furthermore, this phenomenon appears to be influenced by environmental conditions such as pH. A pH of about 4.0 or less causes acrylamide quenching to decrease to approximately the levels observed in the absence of CT-B. These results may be useful in describing the dynamics of the interaction between cholera toxin and target cell membranes. Moreover, these data could provide clues to the mechanism by which the toxic portion of CT is able to enter the cytoplasm of target cells. PMID- 7873594 TI - Chromatographic evidence for pyrraline formation during protein glycation in vitro and in vivo. AB - Pyrraline (epsilon-2-(formyl-5-hydroxymethyl-pyrrol-1-yl)-L-norleucine) is an advanced Maillard reaction product formed from 3-deoxyglucosone in the non enzymatic reaction between glucose and the epsilon-amino group of lysine residues on proteins. Although its presence in vivo as well as in in vitro incubations of proteins with sugars has been documented by immunochemical methods using polyclonal and monoclonal antibodies, its formation in proteins has recently been questioned by similar methodology. To clarify this issue, we investigated pyrraline formation in proteins following alkaline hydrolysis and quantitation by high-performance liquid chromatography on a C18 reverse-phase column. Time- and sugar concentration-dependent increase in pyrraline formation was noted in serum albumin incubated with either 100 mM glucose or 50 mM 3-deoxyglucosone. Formation of pyrraline from 3-deoxyglucosone was rapid at slightly acidic pH, confirming its synthetic pathway through this Maillard reaction intermediate. Low levels of pyrraline (< 10 pmol/mg protein) were also detected in a pool of human skin collagen by this method, but no age effect was apparent. Using a slightly different approach, pyrraline-like material was detected in human plasma proteins following enzyme digestion and analysis by high performance liquid chromatography. Plasma from diabetic patients showed a significant increase in pyrraline-like material compared to controls. The levels in diabetic and normal individuals were 21.6 +/- 9.56 and 12.8 +/- 5.6 pmol per mg protein, respectively (P = 0.005), reflecting thereby the elevated levels of the immediate precursor of pyrraline, 3-deoxyglucosone, in diabetic plasma. PMID- 7873595 TI - The 40 kDa 63Ni(2+)-binding protein (pNiXc) on western blots of Xenopus laevis oocytes and embryos is the monomer of fructose-1,6-bisphosphate aldolase A. AB - A Ni(2+)-binding protein (pNiXc, 40 kDa), present in Xenopus laevis oocytes and embryos, was isolated from mature oocytes by chromatography on DEAE-cellulose and cellulose phosphate, followed by FPLC on Ni-iminodiacetate-Agarose, or reverse phase HPLC on a C-4 column. Size-exclusion HPLC showed that intact pNiXc is approximately 155 kDa, consistent with tetrameric structure. After cleavage with Lys-C proteinase or cyanogen bromide, six peptides were separated by HPLC and sequenced by Edman degradation, providing sequence data for 83 residues. Data base search showed similarity of pNiXc to eukaryotic aldolases, with 96% identity to human aldolase A. pNiXc demonstrated aldolase activity with fructose 1,6 bisphosphate as substrate (Km, 30 microM Vmax 26 mumol min-1 mg-1); the aldolase activity was inhibited non-competitively by Cu2+, Cd2+, Co2+, or Ni2+. Equilibrium dialysis showed high affinity binding (Kd, 7 microM) of 1 mole of Ni per mole of 40 kDa subunit. Based on metal-blot competition assays, the abilities of metals to compete with 63Ni2+ for binding to pNiXc were ranked: Cu2+ >> Zn2+ > Cd2+ > Co2+. This study identifies pNiXc as the monomer of fructose-1,6 bisphosphate aldolase A, and raises the possibility that aldolase A is a target enzyme for metal toxicity. PMID- 7873596 TI - An extremely thermostable aromatic aminotransferase from the hyperthermophilic archaeon Pyrococcus furiosus. AB - Pyrococcus furiosus is a strictly anaerobic archaeon (formerly archaebacterium) that grows optimally at 100 degrees C by the fermentation of peptides. Cell-free extracts were found to contain two distinct aromatic aminotransferases (ArAT, EC 2.6.1.57), one of which was purified to electrophoretic homogeneity. P. furiosus ArAT is a homodimer with a subunit M(r) value of 44,000 +/- 1000. Using 2 ketoglutarate as the amino acceptor, the purified enzyme catalyzed the pyridoxal 5'-phosphate (PMP)-dependent transamination of phenylalanine, tyrosine and tryptophan with respective kcat values of 253, 72 and 62 (s-1 at 80 degrees C) under saturating conditions. The Km values for all three amino acids were between 1.1 and 2.1 mM and the optimum temperature for catalysis was above 95 degrees C. The melting point for the pure enzyme was also above 95 degrees C as determined by the change in ellipticity at 220 nm. Irreversible denaturation of the pure enzyme was not apparent after 6 h at 80 degrees C in the presence of PMP and 2 ketoglutarate and the time required for a 50% loss in activity at 95 degrees C was approx. 16 h. This decreased to approx. 12 h if cofactor and substrate were not added. In contrast, the apoenzyme (lacking PMP) lost most (70%) of its activity (measured after reconstitution) after 6 h at 80 degrees C, indicating that both PMP and 2-ketoglutarate stabilize the enzyme at extreme temperatures. Although few ArATs have been characterized to date, the molecular properties and substrate specificity of P. furiosus ArAT more resemble those of the ArAT from Escherichia coli than those of the analogous enzyme from rat liver. Moreover, the P. furiosus enzyme is by far the most thermostable aminotransferase of any type to be purified so far. PMID- 7873597 TI - The role of histidine residues in the catalytic act of cyclomaltodextrin glucanotransferase from Bacillus circulans var. alkalophilus. AB - Our previous study on cyclomaltodextrin glucanotransferase (CGTase) by chemical modification implied the importance of one or two histidine residues in the cyclization reaction of the enzyme. Based on a computer modelled three dimensional structure of the CGTase, five histidine residues were chosen as targets for the site-directed mutagenesis. The histidine residues 98, 140, 233 and 327 were replaced by aspartate and His-177 by proline using polymerase chain reaction-mediated techniques. The CGTase variants H98D, H140D, H233D and H327D resulted in a profound decrease in the cyclizing and amylolytic activities, while mutation H177P had little influence on the activities but affected the thermal stability and the width of the pH optimum. It is suggested that His-98 functions as (or as a significant part of) the subsite 2 for the binding of the substrate in CGTase and therefore H98D destabilizes the intermediate for cyclization, but does not markedly affect the hydrolytic reactions. Mutants H140D and H233D produced only minor amounts of alpha-cyclodextrin, did not exhibit substrate inhibition with maltotriose and showed non-Michaelis-Menten kinetics. It is proposed that the variants H140D, H233D and H327D cause steric hindrances near the active center, while mutation H177D has similar consequences on the same site spatially. PMID- 7873598 TI - Cloning and expression of the gene of hemocytin, an insect humoral lectin which is homologous with the mammalian von Willebrand factor. AB - Invertebrate lectins play an important role in a non-specific self-defense mechanism, as invertebrates do not synthesize specific antibodies. We report the cloning of several overlapping cDNAs encoding the entire silkworm (Bombyx mori) lectin, which we propose to call hemocytin. The sequence (10477 bp) encoded 3133 amino acids. The characteristics features of the carbohydrate-recognition domain of C-type animal lectin were revealed at C-terminal sequence of hemocytin. When cDNA encoding this region was introduced into baculovirus vector, hemagglutinating activities were detected in the culture fluid of a recombinant virus-infected cells. These activities were inhibited by D-mannose, N-acetyl-D galactosamine, and D-maltose which are haptenic saccharides of authentic hemocytin. Analysis of dot and Northern blot hybridization revealed that hemocytin gene was transcribed in hemocytes of the silkworm at larval-pupal metamorphosis and/or after the injection of Escherichia coli and lipopolysaccharide. After silkworm larvae were injected with C-terminal portion of hemocytin, aggregation of hemocytes was observed in the hemolymph. Hemocytin has significant homology with mammalian von Willebrand factor which involves in platelet adhesion to subendothelium. Also, hemocytin has a homologous region with coagulation factor V and VIII. These results suggest that hemocytin molecule is an adhesive protein and relates to hemostasis or encapsulation of foreign substances for self-defense. PMID- 7873599 TI - A monoclonal antibody generated against a recombinant peptide fragment of the B3 domain of carcinoembryonic antigen reacts with intact carcinoembryonic antigen. AB - The chemical synthesis of a gene coding for a polypeptide of 77 amino acid residues (designated ceaB3) representing a fragment of the CEA-B3 domain of carcinoembryonic antigen (CEA) was achieved. The ceaB3 fragment was cloned into the plasmid pLZPWB1 at the C-terminus of a derivative lacZMF of the lacZ gene, devoid of methionine and cysteine amino acid residues. The fusion protein lacZMF ceaB3 represented approx. 30% of total proteins expressed after induction. The fusion protein was formed as inclusion bodies. Simple washing steps led to an insoluble fusion protein which was of approx. 80% purity. Another fusion gene was generated by inserting ceaB3 between the malE gene encoding maltose binding protein (mbp) and lacZ alpha of the pmal-c2 vector. Expression of the resulting pmal-c2-ceaB3-lacZ alpha yielded the fusion protein mbp-ceaB3-lacZ alpha with a molecular mass of 57.94 kDa, which was obtained as a soluble protein in almost homogeneous form after affinity chromatography employing amylopectin. Polyclonal sheep anti-CEA antiserum specifically reacted with fusion proteins lacZMF-ceaB3 and mbp-ceaB3-lacZ alpha. A monoclonal antibody CEA/HK2 was generated employing lacZMF-ceaB3 for immunization and CEA for screening purposes. The mAB CEA/HK2 specifically recognized CEA in immunoblots. The described experimental strategy should be generally applicable for generation of fusion proteins. These fusion proteins are suitable for epitope characterization of existing antibodies, production of regiospecific polyclonal or monoclonal antibodies. PMID- 7873600 TI - The alpha-subunit mRNAs for Gs and Go2 are differentially regulated by protein kinase A and protein kinase C in rat Sertoli cells. AB - In the present study, we have examined regulatory effects of protein kinase A and protein kinase C activation by 8-CPTcAMP and TPA, respectively, on mRNAs for various G protein alpha-subunits and corresponding immunoreactive proteins in rat Sertoli cells. Gs alpha and Go alpha mRNA levels were transiently increased 1.5 fold and 4-fold, respectively, by 8-CPTcAMP in cultured Sertoli cells. This up regulation of mRNAs for Gs alpha and Go alpha was also observed when Sertoli cells were incubated in the presence of FSH. When protein synthesis was inhibited by cycloheximide, the cAMP-mediated stimulation of Gs alpha mRNA was abolished, whereas Go alpha mRNA was superinduced to a 50- to 100-fold higher level than basal. Activation of protein kinase C with TPA had a strong, synergistic effect on cAMP-mediated stimulation of Gs alpha mRNA, whereas the cAMP-mediated stimulation of Go alpha mRNA was completely blocked. Surprisingly, changes in mRNA levels were not accompanied by any alterations in the levels of immunoreactive Gs alpha and Go alpha proteins. PMID- 7873601 TI - Induction and processing of promutagenic O4-ethylthymine lesion in specific gene segments of plasmid DNA. AB - High affinity antibodies were used for the quantitative assessment of the miscoding O4-ethylthymine (O4-EtThy) base lesion in nanogram amounts of membrane transblotted restriction fragments of ENU treated DNA. The polyclonal antibody (TB3) specifically recognized attomoles of the alkylation adducts in modified DNA with no cross-reactivity to an excess of unmodified DNA. The sensitivity of the immuno-quantitative method was determined to be in the range of 76 attomoles to 2.43 fmol, corresponding to 0.24 x 10(-7) to 7.9 x 10(-7) adducts per nucleotide in plasmid DNA. Modification levels in ras and tk genes were estimated as 0.025 and 0.014 adducts respectively. Specific antibody binding was proportional to the dose of ENU and size of the DNA fragments. In differentially ethylated ras gene, the amount of O4-EtThy was quantified as 0.026, 0.08 and 0.13 adducts per gene fragment. A DNA concentration dependent antibody binding was observed with large (23.13 and 9.41 kb) and smaller (2.02 kb) fragments of HindIII digested ENU treated phage lambda DNA. To monitor the repair of O4-EtThy lesions in specific segments, damage was assessed in sequences of plasmid DNA established in various Escherichia coli strains. The loss of antibody binding to O4-EtThy adducts in ethylated DNA fragments of 6.4 kb ras gene and 3.6 kb tk gene occurred with an approximate t1/2 of 45 and 35 min, respectively, in the repair proficient wild type E. coli. On the contrary, no repair was seen in the alkyltransferase deficient double mutant ada-ogt- strain. The results specifically demonstrate the sensitivity of the immunological technique and the unique ability of the O4-EtThy specific antibodies to scan this promutagenic base lesion and its repair in very small amounts of selected gene segments in DNA. PMID- 7873602 TI - Isolation and molecular cloning of human sorcin a calcium-binding protein in vincristine-resistant HOB1 lymphoma cells. AB - A vincristine-resistant lymphoma cell line (HOB1/VCR1.0) that is resistant to 1.0 microM of vincristine has been established from a human immunoblastic B lymphoma cell line, HOB1. HOB1/VCR1.0 cells demonstrated the typical multidrug resistant phenotypes. Using two-dimensional gel electrophoresis, we discovered one protein with a molecular mass of 22 kDa and pI 5.7 that was overexpressed in HOB1/VCR1.0 cells. This protein was purified to the degree of apparent homogeneity by preparative isoelectric focusing and sodium dodecylsulfate-polyacrylamide gel electrophoresis. The identification of this protein with sorcin was revealed by comparing the internal amino acid sequence of three Lys-C digested peptides from the purified protein with the sequence previously determined for hamster sorcin. The complete primary structure of the human sorcin was deduced from nucleotide sequence analysis of its cDNA clones. It is composed of 198 amino acid residues with a calculated molecular weight of 21,676, and its sequence is highly similar to that of hamster sorcin (95%). Direct-binding assay with calcium showed that human sorcin is a calcium-binding protein with four 'E-F hand' structures typical of calcium-binding sites. Like the sorcin of hamster, two of the calcium-binding sites of human sorcin contain putative recognition sites for cAMP-dependent protein kinase. Southern and Northern blot analyses showed that the human sorcin gene was greatly amplified and overexpressed in resistant HOB1/VCR1.0 cells but not detected in the parental HOB1 cells. The overproduction of this protein in resistant cells implies that sorcin plays a role in expression of the resistant phenotype. PMID- 7873603 TI - Effect of the 3'-untranslated region on the expression levels and mRNA stability of alpha 1(I) collagen gene. AB - Changes in the synthesis of type I collagen, a major extracellular matrix component in skin and bones, are associated with both normal growth or repair processes and with several pathological conditions such as lung fibrosis and liver cirrhosis. The expression of the alpha 1(I) collagen gene is regulated by transcriptional and post-transcriptional mechanisms. Regulation at both these levels are usually utilised when extensive changes occur in collagen synthesis. We constructed plasmids carrying the whole or partially deleted 3'-UTR sequences of the alpha 1(I) collagen gene, fused to two hGH exons and to the promoter of the alpha 1(I) collagen gene. A control plasmid contained the 3'-UTR of the hGH gene. In transient transfections into Rat-1 fibroblasts, no significant differences between plasmids were found, which suggests that although 3'-end of the gene has been shown in previous studies to contain DNaseI hypersensitive sites and to bind sequence-specific nuclear proteins it does not seem to function as a transcriptional regulator. This was further supported by the finding that TGF-beta treatment induced a 2.5-fold expression of hGH mRNA from plasmids containing collagen promoter and either hGH or alpha 1(I) collagen 3'-UTR. In stable transfections, mRNAs using the first polyadenylation site were not as stable as those transcribed from the endogenous alpha 1(I) collagen gene. We suggest that the 3'-UTR alone may not be sufficient to determine the stability of the shorter alpha 1(I) collagen mRNA species. PMID- 7873604 TI - Regulation of melanotransferrin gene in melanoma cells. Analysis of the enhancer region. AB - The human iron-binding protein melanotransferrin is up-regulated in most skin melanomas. With the goal to understand the mechanisms controlling the expression of the gene in these tumor cells, we previously reported the identification of an enhancer exhibiting melanoma specificity. We show here that, in the highly expressing SK-MEL-28 melanoma cell line, the chromatin structure in the enhancer region is in an open configuration and that the transcription factors governing its activity belong to the helix-loop-helix and the Jun/Fos leucine zipper families. PMID- 7873605 TI - DNA binding activity of the glucocorticoid receptor is sensitive to redox changes in intact cells. AB - The effect of changes of redox conditions on glucocorticoid receptor (GR) activity in intact cells has been studied using two approaches. One was to evaluate the GR-DNA binding in extracts of COS2 cells transiently overexpressing GR and in which reactive oxygen intermediates (ROI) accumulate as a consequence of glutathione (GSH) depletion. GR-DNA binding was significantly decreased in COS2 cells treated with diethylmaleate (DEM), which causes GSH depletion by forming GSH-DEM complexes. A similar effect was observed for Sp1, another Zn finger transcription factor, whereas no difference was observed for the C/EBP transcription factor, which is known to be unaffected by redox changes in vitro. N-Acetylcysteine (NAC), which counteracts the effects of DEM by increasing GSH biosynthesis, prevents the decrease of GR-DNA binding in cells treated with DEM. The GR-DNA binding efficiency was similarly decreased using extracts from H2O2 treated COS2 cells and from COS2 cells treated with buthionine sulphoximine, which causes GSH depletion via a mechanism different from that of DEM. The other approach was to evaluate the efficiency of a GR-regulated promoter under different redox conditions. In HeLa cells, transfected with a plasmid containing the CAT gene under the control of the glucocorticoid responsive element (GRE) within the mouse mammary tumor virus promoter, and treated with dexamethasone to activate GR, exposure to DEM significantly impaired the activation of CAT gene expression induced by dexamethasone. Also in this case NAC treatment inhibited the effects of DEM. PMID- 7873606 TI - Isolation and expression during pollen development of a tobacco cDNA clone encoding a protein kinase homologous to shaggy/glycogen synthase kinase-3. AB - We have isolated a tobacco (Nicotiana tabacum L.) cDNA clone encoding a putative serine/threonine protein kinase, which shows highest homology to previously described families of alfalfa and Arabidopsis protein kinases and to their homologues rat glycogen synthase kinase-3 and Drosophila shaggy kinases. Northern experiments showed that NtK-4 is expressed in all sporophytic tobacco tissues tested, as well as in gametophytic and embryogenic pollen. PMID- 7873608 TI - Sequence analysis and exclusion of phosducin as the gene for the recessive retinal degeneration of the Abyssinian cat. AB - Phosducin was evaluated as a candidate gene for the recessive retinal degeneration in the Abyssinan cat, rdAc, using reverse transcription and polymerase chain amplification. The nucleotide sequence of the cat phosducin coding region was determined except for 23 bp at the 5' end. Single-strand conformation analysis of a silent polymorphism within the coding region established the nonlinkage of the phosducin gene with the rdAc locus. PMID- 7873607 TI - Mouse sepiapterin reductase: an enzyme involved in the final step of tetrahydrobiopterin biosynthesis. Primary structure deduced from the cDNA sequence. AB - We carried out the cloning of a mouse cDNA encoding a sepiapterin reductase which is involved in the final step of tetrahydrobiopterin biosynthesis as a first step toward gene-targeting technique in mice. The sequence contained 1245 nucleotides consisting of an open reading frame of 783 nucleotides encoding a protein of 261 amino acid residues whose molecular weight was 27,851, a 5'-untranslated region of 21 nucleotides and a 3'-untranslated region of 441 nucleotides containing poly(A) tail. The amino acid sequence of mouse sepiapterin reductase revealed the identity of 88% with rat and 74% with human sequence. PMID- 7873609 TI - Nucleotide sequence and peptide motifs of mouse uromodulin (Tamm-Horsfall protein)--the most abundant protein in mammalian urine. AB - The mouse uromodulin cDNA sequence was sequenced. The predicted peptide sequence is 642 amino acids long and contains several modular components including four epidermal growth factor like repeats, one betaglycan-like domain (ZP domain), and a consensus sequence for attachment of a glycosyl-phosphatidyl-inositol anchor. An arginine-glycine-aspartate tripeptide reported for rat and human sequence is absent in the mouse. There are several potential sites for post-translational modification. PMID- 7873610 TI - Molecular cloning of a human complementary DNA encoding an initiation factor 2 associated protein (p67). AB - Rat p67 is an initiation factor-2 associated protein, which plays important roles in translational regulation. A cDNA that encodes a homologue of rat p67 was isolated from a human liver cDNA library. The encoded protein contains 478 amino acids with a calculated molecular mass of 52,891 and an isoelectric point of 5.64. The amino acid sequence is 92% identical to that of rat p67. The corresponding mRNA has a size of approximately 2.1 kb and is present in all tested human tissues. PMID- 7873611 TI - Characterization of the cDNA and three processed pseudogenes from the murine protein kinase CK2 alpha subunit. AB - Seven protein kinase CK2 alpha clones were isolated from a murine genomic DNA library. They were assigned to four different genomic loci (A,B,C,D). Locus D was previously identified as a processed pseudogene (Boldyreff et al. (1992) Biochem. Biophys. Res. Commun. 186, 723-730). Here we present sequences of genomic loci B and C and the murine CK2 alpha cDNA. Loci B and C are like locus D processed pseudogenes, however, with considerable differences among each other and to the cDNA, especially with respect to the lengths of the putative gene products. Genomic locus D would code for a protein of 82 amino acids, locus B for a protein of 132 amino acids and locus C product for the full length product of 391 amino acids as the murine cDNA. PMID- 7873612 TI - A novel CYP3 gene from female rats. AB - A cDNA library constructed from adult female Sprague Dawley rat liver was screened with polyclonal anti CYP3A-IgG. One of the positive clones, cUT, was found to contain the complete coding sequence of a new gene more similar to hamster gene CYP3A10 (cDNA: 85%, deduced amino acid sequence: 79%) than to the known rat CYP3A genes (cDNA: 75-76%, amino acid sequences: 66-69%). The deduced sequence of the first 28 amino acids is identical to the N-terminus of the testosterone 6 beta-hydroxylase, 6 beta-2 (Nagata, K., Gonzalez, F.J., Yamazoe, Y. and Kato, R. (1990) J. Biochem. 107, 718-725). Northern blots show the presence of cUT mRNA in livers of adult female and male rats. The transcription of the new gene is enhanced in either sex by pregnenolone-alpha-carbonitrile, dexamethasone, phenobarbital, and triacetyloleandomycin, known inducers of CYP3A gene expression. PMID- 7873613 TI - Nucleotide sequence of a cDNA for mouse squalene epoxidase. AB - A full-length cDNA encoding mouse squalene epoxidase was isolated by screening a mouse liver cDNA library with the rat squalene epoxidase gene as a probe. The cDNA had an open reading frame for a 572 amino acid polypeptide with a calculated molecular mass of 63.8 kDa. The predicted amino acid sequence of the mouse enzyme contained an FAD-binding motif, and was 93% identical to that of the rat enzyme. The former is one amino acid shorter than the latter. Blotting analyses showed that the mRNA is 2.8 kb in size and that a single copy of the gene is present in the mouse genome. PMID- 7873614 TI - Several splicing variants of isl-1 like genes in the chinook salmon (Oncorhynchus tschawytscha) encode truncated transcription factors containing a complete LIM domain. AB - Several novel cDNA clones have been isolated from a chinook salmon pituitary cDNA library. Sequence analysis of these clones indicates that they are closely related to the rat LIM domain homeobox gene, isl-1. Due to differential splicing, several of the clones encode truncated polypeptides containing a complete copy of the LIM domain without the homeodomain and C-terminal activation domain. The roles of these truncated polypeptides are discussed. PMID- 7873615 TI - The 3'-untranslated region of rat lysyl oxidase cDNA. AB - The cloning of the 3'-untranslated region of rat lysyl oxidase cDNA was completed. cDNA clones were generated by reverse transcriptase PCR from neonatal rat aorta smooth muscle cell RNA, and sequenced. Several polyadenylated clones were obtained, providing 2.1 kb of new sequence. Clones were polyadenylated at three different positions. The cDNA clones were verified by PCR-cloning and sequencing of genomic DNA, and by Northern blotting studies. Evidence is presented that the polyadenylation patterns of rat lysyl oxidase mRNAs are similar, but not identical to mouse or human transcripts. Interestingly, the nonconsensus polyadenylations in rat did not occur at the same positions as was found in mouse lysyl oxidase cDNAs. Multiple transcription initiation sites were found by primer extension mapping. Thus, the complex pattern of rat lysyl oxidase mRNAs on Northern blots is principally due to differential use of polyadenylation signals, and to the occurrence of multiple transcription initiation sites. All clones lacked a previously reported 258 bp segment nearly identical to a conserved segment of the 3'-untranslated region of elastin cDNA. We conclude that the elastin-like sequence previously reported in rat lysyl oxidase cDNA is not a species-specific sequence, and most probably resulted from spurious ligation reactions during construction of the cDNA library. PMID- 7873616 TI - Cloning, sequence analysis, and expression of a mouse cDNA encoding cytochrome c oxidase subunit VIa liver isoform. AB - A cDNA encoding cytochrome c oxidase (COX) subunit VIa liver isoform (COX6aL) was isolated from a Mus musculus library and sequenced. The protein translated from the nucleotide sequence contains a presequence and is 91% identical to the human cognate sequence over the processed polypeptide region. Northern analysis shows the expression of COX6aL is developmentally regulated in heart, being about equally transcribed with the heart isoform (COX6aH) in 18-day embryos but consisting of less than 25% in adult heart. PMID- 7873617 TI - Nucleotide sequence of the 5'-flanking region of the rat type II hexokinase gene. AB - In a previous study, we found that the steady state transcript level of type II hexokinase was specifically and remarkably elevated in rat hepatoma AH130 cells. To determine the molecular mechanism of transcriptional control of the type II hexokinase gene, we examined the nucleotide sequence of its 5'-flanking region and analyzed putative transcription factor binding sites. We also examined the type II hexokinase promoter activity by the chloramphenicol acetyltransferase (CAT) assay. PMID- 7873619 TI - [Microcalorimetric study of the effect of mitoxantrone on chromatin DNA in vivo]. AB - The influence of antitumor drugs--mitocsantron on the chromatine of tumor cells spleen tissue of BALB/c-mice has been established. Two-stage denaturation process of chromatine in normal cells has been shown. The first stage--thermolabel domain can be described by the following transition parameters: Td1 = 72, delta Td1 = 6.2 degrees C, Qd1 = 36.5 J/g DNA; the second one-thermostable domain by Td2 = 83, delta Td2 = 9.0 degrees C kappa Qd2 = 58 J/g DNA. PMID- 7873618 TI - Determination of the molecular lesions associated with loss-of-function transformer alleles of Drosophila melanogaster. AB - Three mutant alleles of the transformer locus, trav1, trav2 and traenu, were analyzed genetically, and all were found to be functionally null alleles. The DNA sequences of these mutants revealed that they represent nonsense mutations that potentially encode truncated Tra polypeptides of 12, 61, and 90 amino acids, respectively. PMID- 7873621 TI - [Comparative effect of polymyxin B on lipid bilayer membranes with different lipid composition]. AB - The aim of the work was to characterize the role of negatively charged lipids (cardiolipin and lauric acid) in the increase of ionic permeability of the membrane under the action of polymyxin B. Cardiolipin or lauric acid were added into membrane-forming solution in concentration close to that in the membrane of bacterial cell. It resulted in modification of membranes by these lipids. The obtained membranes had a higher ionic permeability in the presence of polymyxin B. However the comparison of different effects can lead to the conclusion that free fatty acid are responsible for the major part of the effect. It is concluded that the character of damage of the bilayer by polymyxin is diverse: polymyxin B forms ionic canals with lauric acid, whereas there is unspecific destruction of BLM by the polymyxin interacting with cardiolipin. PMID- 7873620 TI - [Thermal stability of erythrocyte membrane proteins at varying ionic strength and media composition]. AB - Varying the ionic strength and environmental composition differently affected the thermostability of certain protein blocks in the erythrocyte membrane. As the salt concentration in the solution enhanced, the redistribution of the system of intra- and intermolecular noncovalent bonds occurred, which induced changes in the membrane proteins structure resulting in an increase in the thermostability of both the integral and cytoplasmic band 3 domains and its associated band 4.2. The thermostability of the skeleton junction proteins (actin, 4.1 and 4.9) decreased. The thermostability of the spectrin changed insignificantly. The interaction of Mg2+ and Cu2+; but not Ca2+ ions with the membrane resulted in dynamic quenching the tryptophan fluorescence of the membrane proteins, unchanging their thermostability. Ca2+ ions induced the aggregation of erythrocyte membranes with increasing the temperature. PMID- 7873622 TI - [Potentiation of the effect of polymyxin on the ionic permeability of erythrocytes and lipid bilayer membranes from erythrocyte lipids]. PMID- 7873623 TI - [Participation of a Ca2+-binding glycoprotein with a molecular weight of 40 kDa in the electrogenic Ca2+ transport system in mitochondria]. PMID- 7873624 TI - [Kinetics of ethanol-induced lysis of human erythrocytes]. AB - Hemolysis of human erythrocytes induced by the high ethanol concentrations involves several stages, which are reflected by the kinetic curves of hemolysis. These stages are of colloid-osmotic nature. Ethanol denaturation of membrane proteins and their subsequent aggregation can be responsible for appearance of defects, pores, in the erythrocyte membrane. About 15 ethanol molecules participate in formation of one pore. Sucrose weakly diffusing through the formed pores inhibits the ethanol-induced hemolysis of erythrocytes. On the contrary, the hyperosmotic contraction of erythrocytes in the NaCl- or KCl-containing medium increases the efficiency of the hemolysis. The maximum stability of the erythrocytes to the ethanol action is at the pH 7.2-7.3. PMID- 7873625 TI - [Emergence of a quasi-periodic spatial structure in the model of aggregation of moving, dividing cells, possessing chemotactic properties]. AB - It has been analyzed the Keller-Segel model of aggregation of divided cells possessed hemotaxis. During the cell division homogeneous stationary distribution becomes unstable due to increasing of the common cells amount. It is shown that accidental variation of the primary stable homogeneous stationary distribution result to forming of a like periodical space structure with characteristic scale that basically is defined by the cell division rate. This approach allows to explain the arising of complex space structures in the movable bacterium colonies. PMID- 7873626 TI - [Change in the aggregation ability of rabbit thymocytes under the combined effect of UV-radiation and extremely high frequency radiation]. AB - The number of thymocytes, which have ability to aggregate with homologous erythrocytes, increases under action of the 254 nm UV-radiation at low fluences of 100-350 J/m2 similar action of ultra high frequency (UHF) radiation (46.12 GHz). The number of the active cells decreases during their incubation in the dark after irradiation, i.e. the inactivation after-effect is produced by UV radiation. The thymocyte inactivation by UV-radiation at high fluences is enhanced if the cell suspension is preliminary irradiated with UHF-radiation at low intensity. PMID- 7873627 TI - [Quantitative description of the morphological structure of aggregated cellular elements in blood]. AB - We introduce indices which characterize morphological structure of the system of aggregated cells in a thin blood layer. The main quantitative characteristics of the system is the multifractal spectrum f(alpha). Analysis of the f(alpha) profile for varying aggregation moments allows to describe quantitatively the dynamics of formation and growth of cell aggregates as well as to determine the structural morphological changes during this aggregation. Other quantitative values describing the aggregation kinetics are the scaling exponents characterizing the power dependence of the cluster quantity ns(t) on the number of particles in the cluster s and on the time moment t. PMID- 7873628 TI - [The role of Ca2+, entering the cell during reperfusion, in the mechanism of initiation and maintenance of reperfusion arrhythmias]. AB - The role of calcium ions entering cells upon reperfusion of ischemic myocardium for reperfusion arrhythmias has been investigated on the model of isolated rat right ventricle perfused through coronary artery. Manipulation by concentration of calcium ions in the reperfusion solution demonstrates that calcium ions entering cells upon reperfusion do not play a major role in the initiation of reperfusion extrasystoles and tachycardias, but have a significant influence on the maintenance of tachycardias. Multielectrode mapping revealed a focal source as the mechanism underlying reperfusion arrhythmias at low concentration or in the absence of calcium ions in the reperfusion solution. PMID- 7873629 TI - [Use of a neodymium lasers for fluorescent diagnosis and photodynamic destruction of tumors]. AB - Fluorescence and photodynamic destruction of tumor tissues containing hematoporphyrin derivative was studied during excitation by II and III harmonics of AY:Nd(3+)-laser. This laser system can be effectively used for diagnosis of malignant tumours and photodynamic therapy. PMID- 7873630 TI - [Electroencephalogram analysis using normalized empirical functions for distributing probabilities]. AB - The basis for use of numerical indices for identification of the central nervous system functional state, is provided. Numerical indices are obtained by secondary processing of electroencephalogram spectra using normalized empirical functions of probability distribution. PMID- 7873631 TI - [The effect of changing boundary conditions on the stress state in the tooth model]. AB - The problem of a vertical load acting on a tooth model under strong fixation of the root is investigated by the method of finite elements. The regions of the tooth fracture are determined. The changes of the tooth stress state caused by bone resorption are analyzed. PMID- 7873632 TI - [New prospects in assessing the absorbed radiation dose by electron paramagnetic resonance]. AB - Spin-lattice relaxation rates of radiation induced and background centers in dental enamel have been investigated by electron spin resonance techniques. It has been found that these centers differ in the value of the saturation half power and the saturation process. Based on these experimental results a new approach to discrimination of the radiation induced signal from the total ESR spectrum of dental enamel is proposed. Comparison of the current methods of radiation dose estimation by the ESR analysis has been performed using the new approach. PMID- 7873633 TI - [Regularities and possible nature of biological precursors of the Dzhirgatal earthquake]. AB - The information about cases of anomalous animals behavior prior the Djirgatal earthquake of October 27th, 1984, with the magnitude M = 6.4 is summarized. The general regularities of this behavior coordinated with the peculiarities of the animals behavior before other earthquakes are revealed. Possible causes of the anomalous animals behavior are discussed, based on comparison of data on biological precursors with the data on other precursors and unusual phenomena. PMID- 7873634 TI - [A simple physical model describing the death of multicellular organisms]. AB - A new model which imitates the behaviour of an alive organism is described. The paper provides a new answer to the question: what are life and death? The dependences of lifetime of mammals on the embryo mass and the body mass are found. The connection between the lifetime of an alive organism and the metabolic rate is described. PMID- 7873635 TI - [Electrostatic interaction and differences in specific and nonspecific interactions of the Lac-repressor with DNA]. AB - To investigate the complexes of lac-repressor with specific and non-specific DNA sequences method of covalent cross-linking of proteins to partially depurinated DNA was used. We have identified the amino acid resides which form cross-links and hence are proximate to DNA. Only lysine 33 is cross-linkable in specific complex. In the case of non-specific complex (at the presents of inducer molecules) lysine 33 remains cross-linkable. Some consequences of these phenomena in aspects of the physical backgrounds of protein-DNA interactions have been discussed. PMID- 7873636 TI - [Decarboxylation of amino acids and peptides in a photoreaction with potassium ferricyanide at 77 K]. AB - We have measured action spectra of formation of radicals in aliphatic amino acids and peptides by reaction of decarboxylation with excited potassium ferricyanide. Peptides are capable to the reaction under longwave absorbtion band excitation, whereas amino acids are stable under these conditions, and decarboxylation occur only under irradiations by lambda < 400 nm. PMID- 7873637 TI - [New criteria in the inverse problem of protein structure formation]. AB - New approach to the inverse protein folding problem has been developed. It is helpful for search amino acid sequences of proteins having certain tertiary structure. Also it looks for the best three dimensional structure among known ones for a given amino acid sequence. We introduced new parameters for delineating geometry and physical properties of protein tertiary structure and new evaluation function to distinguish between correct fold and large number of misfolds. The method can be used for checking de novo constructed proteins and for creating enlarged bank of three dimensional protein structures on the basis of known primary protein structures. PMID- 7873638 TI - [Spatial organization of the globular fragment of calmodulin. 2. Conformational analysis of packing of two domains]. AB - Theoretical conformational analysis of possible packing of two alpha-helical strands has been performed for the amino-acid sequence of N-terminal domains of CaM. It has been shown, that side chains of the antiparallel alpha-strands can interpenetrate and form a structure of the "knobs into holes" type. Such packing is profitable in the energy terms and can serve as an element of supersecondary structure, named "alpha-barrel". A possible conformational mechanism of CaM activation by Ca2+ is discussed in terms of the proposed model. PMID- 7873639 TI - [The effect of serum albumin on the temperature of eutectic formation in binary solutions of organic compounds]. AB - The freezing water solutions of serum albumin in presence of additives of several organic compounds have been studied by 1H NMR spectroscopy. Freezing of the solutes in the protein solvation shells occurs at temperatures 30-50 degrees C higher in analogous double solutions. PMID- 7873640 TI - [Interaction of divalent copper ions with native DNA and its monomers]. AB - The complex formation of Cu2+ ions with the 2'-deoxynucleotide-5'-phosphates of bases in water solution by the UV-spectroscopy method has been established. It was obtained that the N7-atom in dGMP and N3-atom in dTMP are coordinated with copper (Cu) in complexes. The deoxyribonucleotide C can not subtract with the copper (Cu). The constants (K) of Cu-bases binding have been obtained. The K value for purines is greater than for pyrimidines independent of the ribose structure. The ions Cu2+ at formation of complexes with separate nucleotides or natural DNA can cause the conformational transitions in these molecules. Thus the ions Cu2+ interact as with N7 and O6 G, as with N3 and O2 C. It is agreed with model, in which guanosine passes from anti to sin-conformation. The interactions of Cu-ions with G, C and A base pairs in single stranded DNA have been registered. PMID- 7873641 TI - Cyanine dye labeling reagents: sulfoindocyanine succinimidyl esters. AB - A series of new fluorescent labeling reagents based on sulfoindocyanine dyes has been developed. We describe the synthesis and properties of these reagents. They contain succinimidyl ester reactive groups and can be readily conjugated to antibodies, avidin, DNA, lipids, polymers, and other amino-group-containing materials. The labeling reagents are water soluble, pH insensitive, and show much reduced dye aggregation under labeling conditions. One of the reagents, Cy3, can be excited with the 488-, 514- and 532-nm laser lines and is optimally excited with the 546-nm mercury arc line. Another, Cy5, can be excited with the 633-nm HeNe and 647-nm Kr laser lines available with many flow cytometers and confocal laser-scanning microscopes. New laser diodes emitting near 650 nm should also be excellent excitation sources for Cy5. PMID- 7873642 TI - Single-chain immunotoxin fusions between anti-Tac and Pseudomonas exotoxin: relative importance of the two toxin disulfide bonds. AB - Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin in which the variable heavy and light domains of the anti-IL2 receptor antibody, anti-Tac, are connected to each other by a peptide linker and then fused to PE40, a truncated form of Pseudomonas exotoxin (PE). This fusion protein has four disulfide bonds: one in each of the two variables domains, one in domain II (Cys 265-287), and one in domain Ib (Cys 372-379) of PE. To study the importance of the disulfide bonds of the toxin to the activity of single-chain immunotoxins, we constructed mutants in which either the cysteines in the toxin were changed to alanines or the amino acids 365-380 of PE were deleted. We began this study with anti-Tac(Fv)-PE40 and a more active variant, anti-Tac(Fv)-PE40KDEL, in which the carbonyl terminus is changed from REDLK to KDEL. From these proteins we made anti-Tac(Fv)-PE40(4)A and anti-Tac(Fv)-PE40KDEL4A, respectively, by converting cysteins at amino acids 265, 287, 372, and 379 of PE to alanines. This change resulted in a 20-100-fold loss of activity toward human target cells, but no significant change in binding affinity to p55. To determine the importance of the second toxin disulfide bond, we removed amino acids 365-380 from anti-Tac(Fv)-PE40, anti-Tac(Fv)-PE40KDEL, and anti-Tac(Fv)-PE40KDEL4A, resulting in anti-Tac(Fv)-PE38, anti-Tac(Fv)-PE38KDEL, and anti-Tac(Fv)-PE38KDEL2A, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873643 TI - Chemoimmunoconjugate development for ovarian carcinoma therapy: preclinical studies with vinca alkaloid-monoclonal antibody constructs. AB - Preclinical efficacy studies are presented in a human ovarian carcinoma model utilizing several novel conjugation strategies with the KS1/4 monoclonal antibody and derivatives of the vinca alkaloid desacetylvinblastine hydrazide. The chemoimmunoconjugates KS1/4-beta-alanine-methylenemalonic acid ethyl ester-4 decacetylvinblastine 23-hydrazide (KS1/4-BAMME-DAVLB-HY), KS1/4-beta-alanine-5 formylpyrrole-2-carboxylic acid-4-desacetylvinblastine 23-hydrazide (KS1/4-BAP DAVLB-HY), and KS1/4-4-desacetylvinblastine 23-hydrazide were explored in the OVCAR-3 human ovarian carcinoma xenograft model. These conjugates, constructed with variable linker stability between the vinca alkaloid and the antibody, were studied by comparing the route of administration and the treatment schedule. Under these conditions a mean survival time from 28 to 35 days in untreated control animals was observed. Significant increases in survival (i.e. 3-9-fold over untreated control animals) were observed with all the immunoconjugates tested but with varying potency and efficacy dependent on linker strategy. Parallel therapy with equivalent doses of free DAVLB-HY or a non-antigen-binding immunoconjugate did not significantly increase the survival of the animals. These results suggest several chemoimmunoconjugate strategies for site-directed therapy of human ovarian cancer. PMID- 7873644 TI - Photodegradation of the cytosine nucleosides family by water-soluble iron(III) porphyrins. AB - Aqueous solutions of cytosine nucleosides such as cytidine (C),2'-deoxycytidine (dC),2',3'-dideoxycytidine (ddC), and 1-beta-D-arabinofuranosylcytosine (ara-C) were irradiated with visible light in the presence of a water-soluble iron(III) porphyrin photocatalyst (FeIIITMPyP or FeIIITSPP) in air or under an argon atmosphere. HPLC analyses revealed release of cytosine as a dominant reaction. In the case of the irradiations of isomeric C and ara-C, their interconversion was also observed as a minor reaction. Under an argon atmosphere, a stoichiometric reduction of the catalyst into FeIITMPyP or FeIITSPP was observable by UV-vis spectroscopy. Quantum yields for the cytosine release and the catalyst reduction (phi cyt and phi FeII) were very much dependent both on the presence and the stereochemistry of the 2'-OH group. For the FeIIITMPyP case, for example, (a) phi cyt and phi FeII decreased in the order C > ara-C > dC > ddC and (b) oxygen lowered the phi cyt of dC and ddC but not phi cyt of C and ara-C. These results strongly support the previously proposed mechanism, i.e., C and ara-C undergo the reaction via a C2' carbon radical (e.g., eq 4) and dC and ddC undergo the reaction via a C1' or C4' carbon radical (e.g., eq 3). The observed effects of 2 propanol and solution pH suggest that a main reactive species photogenerated from FeTSPP is a free hydroxyl radical (*OH), while that photogenerated from FeTMPyP is probably an iron-coordinated active oxygen species (crypto-OH or Fe = O). PMID- 7873645 TI - Peroxidase-linked anti-basic fibroblast growth factor monoclonal antibody Fab' conjugates: application for two-site enzyme immunoassay and immunohistochemical detection. AB - After conjugating thiol groups in the hinge region of monoclonal antibody (mAb) Fab' fragments specific for basic fibroblast growth factor (bFGF) with maleimido horseradish peroxidase HRP) complexes synthesized by incubation of HRP with the heterobifunctional reagent N-succinimidyl-4-(maleimidomethyl)cyclohexane-1 carboxylate, we developed a fluorometric enzyme immunoassay method based on the sandwiching of the factor between anti-bFGF IgG-coated polystyrene beads and the conjugates, and also an immunohistochemical method for detection of the location of the factor. The discriminatory detection limit by the developed enzyme immunoassay (EIA) was as low as 30 pg/mL. The reproducibility of within- and between-assay series was 6.07-9.18% and 6.28-6.82%, respectively, and the recovery of exogenous bFGF from serum was approximately 98%. The curves generated by the concentrated fraction that eluted at the same position as standard bFGF by size-exclusion chromatography on a TSK 2000SW column were parallel to the curve for standard bFGF. From these results, we consider the developed EIA method to be acceptable in regard to sensitivity, precision, and specificity. Also, without the introduction of any additional signal amplification system, positive immunohistochemical reactions were successfully detected by the HRP-linked anti bFGF mAb Fab' in fibroblastic and endothelial cells, which have already been shown to synthesize and secrete bFGF, indicating that these conjugates provide a useful means for direct immunohistochemical detection of the factor. PMID- 7873646 TI - Synthesis, in vitro kinetics, and in vivo studies on protein conjugates of AZT: evaluation as a transport system to increase brain delivery. AB - Our method to increase the delivery of polar drugs to the central nervous system is via drug-protein conjugates with proteins that interact with and cross brain capillary endothelial cells. As a model for drugs containing a reactive hydroxyl group, AZT was conjugated via a succinate linker to two such protein carriers, the highly cationic histone H1 and an anti-transferrin receptor antibody, OX-26. The protein carriers were selected on the basis of their ability to interact with brain capillary endothelial cells by absorptive or receptor-mediated events, respectively. An in vitro pH profile of the rate of AZT release indicated that the observed hydrolysis proceeds by a specific base-catalysis mechanism. At 37 degrees C, the release of AZT proceeded at a rate approximately 10-fold faster (Kobs approximately 8 x 10(-4) min-1) than expected for a simple ester (AZT succinate; Kobs approximately 1.25 x 10(-4) min-1). Using simple model systems, product analysis revealed that intramolecular cyclization of the succinate linker accounts for the observed rate enhancement. Drug delivery in vivo was assessed using immunohistochemical techniques and quantitative brain uptake measurements with singly and doubly labeled AZT-OX-26 conjugates. Immunohistochemical staining of brain sections showed the colocalization of AZT and OX-26 in the brain vasculature. Therefore, drug can be linked to the antibody without affecting the targeting property of the antibody. Furthermore, an in vivo time course using radiolabeled conjugate showed that AZT is delivered to the brain capillaries but is not transported into the brain parenchyma with the antibody.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873647 TI - Preparation, characterization, and in vivo biodistribution properties of synthetically cross-linked multivalent antitumor antibody fragments. AB - Two new antibody forms of the general structure F(ab')n (n = 3 or 4) were prepared and tested in vivo as part of an ongoing search for antibody candidates with improved biodistribution properties for cancer immunotargeting applications. The novel multivalent antibody forms, called F(ab')3-x (tribody, 150 kDa, x = cross-linker) and F(ab')4-x (tetrabody, 200 kDa), were constructed through chemical cross-linking of Fab' subunits derived from murine CC49 IgG, a monoclonal antibody which recognizes the tumor-associated antigen TAG-72. Two new chemical reagents (trismaleimide 1 and tetramaleimide 2) were synthesized for use in cross-linking cysteine sulfhydryl groups present on the hinge region of Fab'. Homogeneous Fab' was prepared by mild reduction of F(ab')2 followed by selective reoxidation of interchain disulfide bonds, leaving a single hinge-region cysteine sulfhydryl group available for modification. For biodistribution studies, the parent F(ab')2 fragment was first radiolabeled via lysine amine modification using the isothiocyanate derivative of the 105Rh(BA-2,3,2-tet)Cl2 complex. Both new fragment forms were shown to retain antigen binding ability in vitro using a solid-phase immunoassay. Although isolated yields for F(ab')3-x and F(ab')4-x were low (18 and 4%, respectively), sufficient quantities were prepared for preliminary biodistribution studies in Balb/c mice and, in the case of F(ab')3-x, for a 5-day biodistribution study in tumor-bearing nude mice. A large proportion of the 105Rh-labeled F(ab')4-x was found to accumulate in the liver, possibly indicating an upper size limit for the in vivo use of cross-linked fragments. The biodistribution behavior of 105Rh-labeled F(ab')3-x in both Balb/c and nude mice was intermediate between that of IgG and F(ab')2 for all organs studied. Kidney localization was reduced, while blood circulation time and tumor accumulation were slightly increased, for the trivalent species compared with F(ab')2. The unique biodistribution profile of F(ab')3-x suggests the possible use of this multivalent fragment for in vivo tumor targeting applications. PMID- 7873648 TI - New application of silane coupling agents for covalently binding antibodies to glass and cellulose solid supports. AB - Bifunctional silane reagents (3-iodopropyl)trimethoxysilane (1), (gamma glycidoxypropyl)trimethoxysilane (2), and [1-(trimethoxysilyl)-2-(m- (or p )chloromethyl)phenyl]ethane (3) were used to covalently link goat anti-mouse (GAM) antibodies (Ab) to glass microbeads and cuprammonium rayon hollow-fiber dialyzers. An average of 0.79 and 0.83 microgram of GAM Ab/cm2 was immobilized on the hollow-fiber dialyzers and the glass beads, respectively. The antibodies immobilized on glass microbeads or on hollow-fiber dialyzers were then used to selectively deplete CD34+ cells or CD4+ peripheral blood mononuclear cells (PBMC), respectively. Glass microbeads depleted 80% CD34+ cells with good selectivity, and the hollow-fiber dialyzers depleted an average of 81% CD4+ PBMC. PMID- 7873649 TI - Exploratory photochemistry of fluorinated aryl azides. Implications for the design of photoaffinity labeling reagents. AB - A series of fluorinated aryl azides and fluorinated azidobenzoates were studied by laser flash photolysis techniques. Using the pyridine ylide probe method it was possible to determine whether a singlet nitrene or ring-expanded ketenimine ylide is the trappable intermediate that is generated at ambient temperature. It was determined that two fluorine substituents, ortho and ortho' substituted relative to the azide group, are required to retard ring expansion and allow bimolecular capture of the singlet nitrene. LFP of ortho, ortho' difluorinated aryl azides in methanol produces the ground triplet state of the nitrene. The results are consistent with chemical analysis of reaction mixtures. The implications of this data for the design of photoaffinity labeling reagents are discussed. PMID- 7873650 TI - A laser flash photolysis study of di-, tri- and tetrafluorinated phenylnitrenes; implications for photoaffinity labeling. AB - Several fluorinated aryl azides (2,6 and 2,4-difluorophenyl azide, 2,4,6 triflurorophenyl azide, and methyl 4-azido-2,3,5,6-tetrafluorobenzoate) were studied by laser flash photolysis techniques. In each case, the azides from singlet nitrenes which can be intercepted with pyridine to form ylides. This allowed determination of the rate constant for ring expansion of the singlet nitrene to the dehydroazepine and measurement of the absolute rate constants for reaction of the singlet nitrenes with typical quenchers. PMID- 7873651 TI - Detection of psoralen cross-link sites in DNA modified by psoralen-conjugated oligodeoxyribonucleoside methylphosphonates. AB - Oligodeoxyribonucleoside methylphosphonates conjugated with derivatives of psoralen cross-link with complementary single-stranded RNA and DNA and with duplex DNA targets when irradiated with long wavelength (365 nm) ultraviolet light. The position of cross-linking between pyranone-side adducts of psoralen conjugated oligonucleoside methylphosphonates and DNA can be easily detected by treating the photoadduct with 1 M aqueous piperidine at 90 degrees C for 30 min, followed by analysis on a polyacrylamide gel run under denaturing conditions. This treatment results in hydrolysis of the methylphosphonate linkages and cleavage of the phosphodiester backbone at the cross-link site. Multiple cross linking sites were detected with a single-stranded DNA target which contains four contiguous T residues. This may result from looping out of one or two of the T residues. PMID- 7873652 TI - New amphipatic polymer-lipid conjugates forming long-circulating reticuloendothelial system-evading liposomes. AB - Lipid-conjugates of two amphipatic polymers, poly(2-methyl-2-oxazoline) (PMOZ) and poly(2-ethyl-2-oxazoline) (PEOZ) (degree of polymerization approximately 50) were synthesized by linking glutarate esters of the polymers to distearoylphosphatidylethanolamine (DSPE) or alternatively by termination of the polymerization process with DSPE. Surface-modified liposomes (90 +/- 5 nm) prepared from either conjugate (5 mol % of total lipid) were injected into rats and followed by blood level and tissue distribution measurements. Both polymers PEOZ and PMOZ were found to convey long circulation and low hepatosplenic uptake to liposomes to the same extent as polyethylene glycol (PEG), the best known material for this purpose. This is the first demonstration of protection from rapid recognition and clearance conveyed by alternative polymers, which is equal to the effect of PEG. PMID- 7873653 TI - Target-promoted alkylation of DNA. AB - Inducible and selective alkylation of DNA was accomplished under neutral conditions by use of a silyl-protected phenol that served as a precursor for a highly reactive quinone methide. As expected, addition of fluoride triggered reaction of a model compound, 3-(tert-butyldimethylsiloxy)-4-[(p nitrophenoxy)methyl]benzamide, and its oligodeoxynucleotide conjugate. Surprisingly, the silyl phenol was also specifically yet more slowly activated by the environment of duplex DNA in the absence of fluoride. This alternative process was associated with the hybridization of probe and target strands, and single-stranded DNA was unable to induce a similar activation. Therefore, DNA appears to effect its own alkylation by promoting the formation of an electrophilic and nondiffusible intermediate. PMID- 7873654 TI - Synthesis and primer properties of oligonucleotides containing 3' deoxypsicothymidine units, labeled with fluorescein at the 1'-position. AB - Several analogues of the standard M13 sequencing primer that contain up to five 3'-deoxypsicothymidines, or one or two such units labeled with fluorescein at the 1'-position, have been prepared. All these oligonucleotides have been shown to prime the DNA-polymerase-catalyzed synthesis of DNA. PMID- 7873655 TI - Site-specific conjugation of a temperature-sensitive polymer to a genetically engineered protein. AB - A genetically-engineered mutant of cytochrome b5, incorporating a unique cysteine residue, was conjugated to maleimide-terminated oligo(N-isopropylacrylamide). The conjugation of the protein by reaction of the cysteine residue, precisely positioned by site-directed mutagenesis techniques, with an activated oligomer containing only one reactive end group in the oligomer chain permits the site specific and stoichiometric conjugation of the oligomer with the protein. The protein-oligomer conjugate was shown to exhibit lower critical solution temperature (LCST) behavior, similar to the free oligomer. Furthermore, the LCST behavior of the protein-oligomer conjugate is reversible and allows selective precipitation of the conjugate above its LCST. PMID- 7873656 TI - Psoralen-containing vinyl monomer for conjugation of double-helical DNA with vinyl polymers. AB - We have synthesized a vinyl monomer having a psoralen moiety, which can form a photoadduct with double-helical DNA. The monomer 1 was proved to have an ability to crosslink DNA double strands through a photochemical reaction when irradiated by UV light. The resulting DNA having vinyl groups was copolymerized with a comonomer such as acrylamide and N-isopropylacrylamide to give rise to a DNA vinyl polymer conjugate. A conjugation based on covalent bondings was verified by using gel electrophoresis; the conjugation efficiency was found to be dependent upon concentration of the monomer which had been used in the antecedent photochemical reaction. This monomer will be a useful tool when anchoring double helical DNA on polymeric materials for separating and sensing DNA-binding substances. PMID- 7873657 TI - Analysis of sequences required for the cytotoxic action of a chimeric toxin composed of Pseudomonas exotoxin and transforming growth factor alpha. AB - Chimeric toxins composed of transforming growth factor alpha fused to mutant forms of Pseudomonas exotoxin bind to the EGF receptor and kill cells bearing these receptors. In early experiments, the binding domain of Pseudomonas exotoxin was deleted and replaced with TGF alpha to make TGF alpha-PE40. This chimeric toxin required proteolytic processing within the target cell to be converted to its active form (Siegall et al. (1989) FASEB J. 3, 2647-2652). Subsequently, recombinant toxins that do not require proteolytic processing were constructed by inserting TGF alpha near the carboxyl terminus of domain III and deleting toxin residues up to the processing site at position 280. In addition, the carboxyl terminus of this toxin was converted from REDLK to KDEL to increase its activity. Recombinant toxins of this type, termed PE37/TGF alpha/KDEL, are about 100-fold more potent than TGF alpha-PE40. To determine if other sequences can be removed from such chimeric toxins to make a smaller molecule that can penetrate tissues better, we have carried out a deletion analysis of sequences present within domains II and Ib. We find that all of domain Ib and a portion of domain II can be deleted without significant loss of cytotoxic activity, but larger deletions extending further into domain II lose cytotoxic activity. We also find that inserting a small linking peptide (Gly)4Ser between residual sequences in domain II and domain III, in molecules with diminished cytotoxic activity, enhances cytotoxicity suggesting that one role of domain Ib is to prevent undesirable interactions between domains II and III.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873658 TI - Synthesis and characterization of oligomeric nido-carboranyl phosphate diester conjugates to antibody and antibody fragments for potential use in boron neutron capture therapy of solid tumors. AB - Antibodies conjugated to oligomeric carboranyl compounds have a high potential as target species for boron neutron capture therapy (BNCT) of solid tumors. As a first step toward developing conjugates with BNCT capabilities, an oligomeric nido-carboranyl phosphate diester (Kane, R. R., Dreschel, K., and Hawthorne, M.F. (1993) J. Am. Chem. Soc. 115, 8853-8854), CB10 (10 nido-carboranes containing 90 boron atoms) with a pseudo-5'-terminal amino group, was conjugated to the anticarcinoembryonic antigen antibody T84.66 and its F(ab') fragment. The homobifunctional linker disuccinimidyl suberate (DSS) was coupled to CB10 via its 5'-terminal amino group followed by removal of excess linker with organic solvent extraction and conjugation with intact antibody. Similarly, the heterobifunctional linker, m-maleimidobenzoyl-N-hydroxysuccinimide (MBS), was coupled to CB10 and conjugated to the hinge region sulfhydryl of the F(ab') fragment of T84.66. The extent of reaction was monitored by the mobility shift of CB10-antibody conjugate on native polyacrylamide gels and the increased susceptibility of the CB10-antibody conjugate to staining with silver nitrate. CB10 was also labeled with radioiodine (131I) in a solid phase reaction with iodogen and used in double-label studies with 125I-labeled antibody. Although free CB10 bound very tightly to gel filtration media such as Sephadex G-25, the CB10-antibody conjugate passed through freely. After separation of CB10-antibody conjugate from free CB10 on Sephadex G-25, molar incorporations of CB10 were calculated. At a molar ratio of 10:1 (CB10:T84.66), greater than 90% of T84.66 and 30% of its F(ab)' fragment were conjugated to CB10.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873659 TI - A facile, water-soluble method for modification of proteins with DOTA. Use of elevated temperature and optimized pH to achieve high specific activity and high chelate stability in radiolabeled immunoconjugates. AB - We have developed a method for attachment of the macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane N,N',N",N"'-tetraacetic acid (DOTA) to proteins by activation of a single carboxyl group with N-hydroxysulfosuccinimide (sulfo-NHS). The sulfo-NHS active ester of DOTA was prepared in a single step using 1-ethyl-3 [3-(dimethylamino)propyl]carbodiimide (EDC), and DOTA conjugates of cytochrome c and the anti-carcinoembryonic antigen chimeric monoclonal antibody cT84.66 were prepared by adding the DOTA active ester reaction mixture to the proteins at pH 8.5-9.0. Mass spectrometry of the cytochrome c conjugates showed that as the molar ratio of DOTA active ester to protein in the reaction mixture was increased from 10:1 to 100:1, the average number of chelators attached to the protein molecule increased from 2.64 to 8.79. When DOTA active ester reacted with the antibody at a molar ratio of 100:1, the conjugate averaged 3.8 chelates per antibody. Immunoreactivity of the antibody conjugate radiolabeled with 111In(III) and 90Y(III) remained quantitative. Variation of the DOTA:sulfo-NHS:EDC activation stoichiometry from 2:2:1 to 10:10:1 revealed that the kinetic stability of the radioconjugates increased as the molar ratio of carbodiimide, relative to DOTA and sulfo-NHS, was decreased. Radiolabeling of the protein conjugates with 111In(III) and 90Y(III) proved to be sensitive to pH, buffer, and temperature effects. The optimum pH for the labeling reaction was different for each protein and may be related to the isoelectric point of the protein. Radiometal incorporation at high specific activity was accomplished in acetate and Tris buffers, but the presence of citrate inhibited the labeling reaction. Increasing the temperature of the radiolabeling reaction from 25 to 43 degrees C greatly increased both the efficiency of radiometal incorporation and the kinetic stability of the radioconjugates. Stability studies of the conjugates in human serum and in the presence of a 5000- to 250,000-fold excess of diethylenetriaminepentaacetic acid (DTPA) demonstrated that the radiolabeled proteins are kinetically inert under physiological conditions. In serum, the 111In(III)-labeled antibody showed a rate of radiometal loss of approximately 0.08% per day. In the presence of excess DTPA, both conjugates lost 111In(III) at a rate of about 0.3% per day. No loss of 90Y(III) from the conjugates was observed in serum, but in excess DTPA, both 90Y(III) labeled proteins showed a rate of radiometal loss of approximately 0.2% per day. Therefore, kinetic analysis of metal loss from a radiolabeled immunoconjugate in the presence of a vast excess of DTPA may provide a better indication of the in vivo stability of that immunoconjugate than serum stability studies. PMID- 7873660 TI - Temperature-responsive bioconjugates. 3. Antibody-poly (N-isopropylacrylamide) conjugates for temperature-modulated precipitations and affinity bioseparations. AB - Immunoglobulin G (IgG) has been modified by poly(N-isopropylacrylamide) (PIPAAm) to create a novel bioconjugate which exhibits reversible phase transition behavior at 32 degrees C in aqueous media. A terminal carboxyl group introduced into PIPAAm molecule by polymerization of IPAAm with 3-mercaptopropionic acid was used for conjugation to IgG via coupling reaction of activated ester with protein amino group. These conjugates exhibited rapid response to changes in solution temperature and significant phase separation above a critical solution temperature corresponding to that for the original PIPAAm. These conjugates bound to antigen quantitatively in aqueous system, and antigen-bound complex also demonstrated phase separation and precipitation above a critical temperature. Precipitate was reversibly redissolved in cold buffer. Though particular conjugate which includes 12 molecules of PIPAAm with 6,100 molecular weight suppressed more than 95% of Fc-dependent binding with protein A, it retained approximately 60% of original specific antigen binding activity. It was manifested that polymer content of conjugate was 20-30 wt% for the case of 6,100 molecular weight of PIPAAm to demonstrate specific antigen binding activity most effectively and to reduce Fc-dependent binding with protein A. IgG-PIPAAm conjugates were soluble in water and formed antigen-bound complex in homogeneous solution system below a critical temperature. These conjugates were separated from solution and other solutes corresponding to PIPAAm nature and scarcely bound to antigen above a critical temperature. It is revealed that temperature responsive PIPAAm conjugated to biomolecule operated as a switching molecule. These phenomena are attractive for not only reversible bioreactors and protein separations but also carrier substrate to localize biomolecules such as drugs, peptides and hormones in a living body. PMID- 7873661 TI - Molecular characterization of surface topology in protein tertiary structures by amino-acylation and mass spectrometric peptide mapping. AB - Amino-acetylation and -succinylation reactions in combination with mass spectrometric peptide mapping of tryptic peptide mixtures have been employed for surface topology-probing of lysine residues in bovine ribonuclease A, lysozyme, and horse heart myoglobin as model proteins of different surface structures. Direct molecular weight determinations identifying the precise number of acyl groups in partially modified proteins were obtained by electrospray and 252Cf plasma desorption mass spectrometry. Electrospray mass spectra of multiply protonated molecular ions and deuterium exchange experiments provided a relative conformational characterization of protein derivatives and enabled the direct determinations of intact, partially acylated heme-myoglobin derivatives. Tryptic peptide mapping analysis, using plasma desorption and fast atom bombardment mass spectrometry, ascertained by mass spectrometric characterization of HPLC separated modified peptides, yielded the exact identification of acylation sites. Relative reactivities of the amino acylation were derived from the peptide mapping data and from quantitative estimations of modified peptides upon acetylation/trideuteroacetylation and provided direct correlations with the relative surface accessibilities of lysine-epsilon-amino groups taken from X-ray crystallographic structure data of the proteins. The reactive lysine-41 residue in ribonuclease A which is part of the substrate binding site was directly identified from the mass spectrometric data. These results indicate tertiary structure-selective acylation combined with mass spectrometric peptide mapping as an efficient approach for the molecular characterization of surface topology and reactive fundamental lysine residues in proteins. PMID- 7873662 TI - Multivalent melanotropic peptide and fluorescent macromolecular conjugates: new reagents for characterization of melanotropin receptors. AB - Radioreceptor binding studies have documented the presence of melanotropin receptors on some but not all of the various human melanoma cell lines that have been studied. Using a newly developed class of multivalent fluorescent melanotropin-macromolecular conjugates, we have demonstrated for the first time the presence of specific melanotropin receptors on all of the melanoma cell lines, both mouse and human, melanotic as well as amelanotic, that were investigated. The conjugates developed by us consisted of multiple copies of both a potent melanotropin analogue and a fluorophore, both arranged in a pendent fashion on a biologically inert macromolecule. While the multivalency of these conjugates may have established stronger binding with the melanotropin receptors on the cell surface (perhaps by establishing simultaneous multiple interactions), the presence of multiple copies of the fluorophore also greatly increased the level of detection in fluorescence labeling experiments. Membrane receptor hormone-associated phenomena, such as capping and internalization of the receptor ligand complex, also were observed. The details of these methods are described using B-16 mouse melanoma cells as a model system. The demonstration of MSH receptors as a common marker for melanoma suggests that this methodology might be employed for early clinical detection and anatomical localization of melanoma. These results also offer the possibility that substitution of the fluorophore in these conjugates by a chemical agent of (chemo-)therapeutic relevance may provide a powerful tool for site specific (tumor) targeting and cytotoxicity. PMID- 7873663 TI - Synthesis and characterization of carbohydrate-linked murine monoclonal antibody K20-human serum albumin conjugates. AB - Efficacy of antibody mediated targeting depends on retention of immunoreactivity in conjugates. Retention can be improved by site-specific linkage of drugs or drug-loaded carriers to residues that are located well away from the antigen binding sites. In this study we describe the site-specific linkage of a potential drug carrier, human serum albumin (HSA), to the carbohydrate residues in Dal K20, a murine IgG1 monoclonal antibody (mAb) against human renal cell carcinoma, using disulfide exchange between 3-(2-pyridyldithio)propionic acid succinimidyl ester (SPDP)-derivatized HSA and 11-[[3-(2-pyridyldithio)propionyl]amino]undecanoic acid hydrazide (AUPDP)-derivatized mAb Dal K20. AUPDP gave a higher yield of the conjugate than a functionally analogous 3-(2-pyridyldithio)propionic acid hydrazide (HPDP), suggesting that the extra length of the former facilitated the linkage. The conjugates were found to be unstable without reduction of the hydrazone linkage using sodium cyanoborohydride. Stabilized 1:1 HSA:K20 carbohydrate-linked conjugates were isolated and compared with non-site-specific 1:1 conjugates in which HSA was conjugated to amino groups in mAb Dal K20. The yield and stability of the two conjugates were comparable, but the site-specific conjugate was found to retain three times more antibody activity than the non site-specific conjugate. PMID- 7873664 TI - Targeted delivery of DNA using YEE(GalNAcAH)3, a synthetic glycopeptide ligand for the asialoglycoprotein receptor. AB - In vivo gene therapy shows promise as a treatment for both genetic and acquired disorders. The hepatic asialoglycoprotein receptor (ASGPr) binds asialoorosomucoid-polylysine-DNA (ASOR-PL-DNA) complexes and allows targeted delivery to hepatocytes. The tris(N-acetylgalactosamine aminohexyl glycoside) amide of tyrosyl(glutamyl) glutamate [YEE(GalNAcAH)3] has been previously reported to have subnanomolar affinity for the ASGPr. We have used an iodinated derivative of YEE(GalNAcAH)3 linked to polylysine and complexed to the luciferase gene (pCMV-Luc) in receptor-binding experiments to establish the feasibility of substituting ASOR with the synthetic glycopeptide for gene therapy. Scatchard analyses revealed similar Kd values for both ASOR and the glycopeptide. Binding and internalization of 125I-Suc-YEE(GalNAcAH)3 were competitively inhibited with either unlabeled ASOR or glycopeptide. The reverse was also true; 125I-ASOR binding was competed with unlabeled YEE(GalNAcAH)3 suggesting specific binding to the ASGPr by both compounds. Examination of in vivo delivery revealed that the 125I-labeled glycopeptide complex mimicked previous results observed with 125I ASOR-PL-DNA. CPM in the liver accounted for 96% of the radioactivity recovered from the five major organs (liver, spleen, kidney, heart, and lungs). Cryoautoradiography displayed iodinated glycopeptide complex bound preferentially to hepatocytes rather than nonparenchymal cells. In vitro, as well as in vivo, transfections using the glycopeptide-polylysine-pCMV-luciferase gene complex (YG3 PL-Luc) resulted in expression of the gene product. These data demonstrate that the YEE(GalNAcAH)3 synthetic glycopeptide can be used as a ligand in targeted delivery of DNA to the liver-specific ASGPr. PMID- 7873665 TI - Conjugates of cis-4-hydroxy-L-proline and poly(PEG-Lys), a water soluble poly(ether urethane): synthesis and evaluation of antifibrotic effects in vitro and in vivo. AB - Synthetic approaches for the preparation of macromolecular conjugates of the antifibrotic agent cis-4-hydroxy-L-proline (cHyp) were explored, and the efficacy of the conjugates in inhibiting collagen accumulation was investigated in vitro and in vivo. In one approach, poly(PEG-Lys), an alternating copolymer of poly(ethylene glycol) (PEG) and lysine, was used as the carrier. To prepare pendent chain systems, cHyp was attached to poly(PEG-Lys) through an amide linkage [poly(PEG-Lys-cHyp amide)] or through an ester linkage [poly(PEG-Lys-cHyp ester)]. In an alternative approach, cHyp was incorporated into the backbone of a linear copolymer consisting of PEG, succinic acid, and cHyp units [poly(PEG succinate-cHyp)]. Bioactivity in vitro was assessed by the ability of the cHyp conjugates to inhibit growth of cultured smooth muscle cells (SMC) and rat lung fibroblasts (RLF). Cell numbers were compared to control experiments in the presence of biologically inactive trans-4-hydroxy-L-proline (tHyp). After a 5 day period, the presence of 8 micrograms/mL of cHyp delivered by poly(PEG-Lys-cHyp amide) resulted in a 47% reduction in the number of SMC (p < 0.05), the presence of 36 micrograms/mL of cHyp delivered by poly(PEG-Lys-cHyp ester) resulted in a 38% reduction in the number of SMC (p < 0.05), while the presence of 118 micrograms/mL of cHyp delivered by poly(PEG-succinate-cHyp) resulted in a 31% reduction in the number of cells (p < 0.05). An identical trend was observed for the inhibition of RLF growth. In general, poly(PEG-Lys-cHyp amide) was most active, followed by poly(PEG-Lys-cHyp ester) and the backbone system, poly(PEG succinate-cHyp). Specifically, poly(PEG-Lys-cHyp amide) was over 100-fold more active in inhibiting cell growth than free cHyp. Bioactivity in vivo was evaluated by measuring collagen accumulation in subcutaneously implanted poly(vinyl alcohol) sponges in rats. Among the tested conjugates, poly(PEG-Lys cHyp amide) was most active, reducing collagen accumulation in the sponge by 33% after 14 days relative to controls (p < 0.05). This result indicates that the covalent attachment of cHyp to poly(PEG-Lys) carries may be a useful strategy for the local inhibition of collagen accumulation in tissues. PMID- 7873666 TI - Characterization of protein-hapten conjugates. 1. Matrix-assisted laser desorption ionization mass spectrometry of immuno BSA-hapten conjugates and comparison with other characterization methods. AB - Several different low molecular weight haptens were conjugated to BSA to produce immunogens useful for antibody development. The extent of BSA modification due to covalent attachment of hapten was estimated by matrix-assisted laser desorption ionization mass spectrometry. The average number of hapten incorporated to immunogen was determined from the difference in the measured molecular weights of the conjugate from nonmodified BSA. The results from mass spectrometry were compared with results obtained from other more traditional methods of immunogen characterization (UV analysis, trinitrobenzenesulfonic acid titrations, and gel electrophoresis). In each case we were able to calculate the average number of hapten covalently bound to BSA for each synthetically prepared immunogen using matrix-assisted laser desorption ionization mass spectrometry. The other methods presented limitations in certain cases. PMID- 7873667 TI - High yield, site-specific coupling of N-terminally modified beta-lactamase to a proteolytically derived single-sulfhydryl murine Fab'. AB - The preparation of bispecific protein conjugates capable of performing diverse biological functions is an area of active investigation. Such conjugates are routinely prepared using techniques which employ random derivatization of lysine residues, but the overall utility of these methods is limited due to poor yields and heterogeneous conjugates. In this report we describe the development of site specific linkage methodology for the chemical synthesis of a homogeneous enzyme antibody Fab' conjugate with coupling efficiencies of at least 72%. The N terminal threonine residue of beta-lactamase from the P99 strain of Enterobacter cloacae was oxidized to an aldehyde functional group under mild conditions with a 5-fold molar excess of sodium periodate. The murine Fab' with a single sulfhydryl at the hinge region was generated by further digestion of the peptic Fab' fragment with lysyl endopeptidase to remove a decapeptide containing two of the three cysteine residues. Coupling of the two modified proteins was accomplished through a bifunctional coupling reagent containing meleimide and aminooxy functional groups. Synthesis of the linker is described. Yields of 1:1 enzyme Fab' were at least three times higher than for comparable random derivatization methods. Immunoreactivity and enzymatic activity were unaffected. Biodistribution studies showed a more favorable tumor to blood ratio with the site-specifically linked conjugate. PMID- 7873668 TI - Gene transfer with a series of lipophilic DNA-binding molecules. AB - Synthetic gene transfer vectors could be an attractive alternative to biological vehicles for gene therapy. In an effort to improve the previously developed lipopolyamine-mediated transfection technique, various amphiphilic DNA-binding molecules have been synthesized. Besides Transfectam, several lipospermines display very high gene delivery levels. The structure-activity relationship obtained points to the central role played by the polyamine headgroup in condensing the plasmid and binding it to the cell surface, provided the hydrophobic moiety is capable to generate nonmicellar mesomorphic structures. It also highlights other favorable (albeit more speculative) properties shared by protonable lipospermines as compared to quaternary ammonium-bearing lipids, such as their ability to act as a buffer and their strong affinity for chromatin. The former property may prevent the pH decrease along the degradative lysosomial pathway. The ability to bind to chromatin even in the presence of endogeneous polyamines should have two consequences: a nuclear tropism of the transfecting particles and plasmid uncoating in the nucleus by competitive dilution of the lipopolyamine into an ocean of DNA. PMID- 7873669 TI - [eta 5-Cyclopentadienyl]metal tricarbonyl pyrylium salts: novel reagents for the specific conjugation of proteins with transition organometallic labels. AB - New specific reagents for the conjugation of organo transition metal species to proteins are described. These reagents are pyrylium salts bearing a (eta 5 C5H4)M(CO)3 (M = Mn and Re) at position 4. They couple with simple amines (n butylamine and tert-butylamine) and to lysine side chains of proteins (bovine serum albumin and lysozyme) with varying yields. In almost all cases, the final conjugated species is a pyridinium salt, with the exception of lysozyme, for which the reaction ends at the divinylogous amide form. Differences in reactivity for bovine serum albumin and lysozyme can be explained in terms of differences of isoelectric point and steric local environment around the reactive lysine residue. PMID- 7873670 TI - Preparation and characterization of a bifunctional fusion enzyme composed of UDP galactose 4-epimerase and galactose-1-P uridylyltransferase. AB - A fusion enzyme consisting of UDP-galactose 4-epimerase and galactose-1-P uridylyltransferase with an intervening Ala3 linker was constructed by in-frame fusion of E. coli gene galT to the 3'-terminus of the E. coli gene galE that had been extended with the coding sequence for three alanine residues, all contained within a high-expression plasmid. The fusion enzyme was expressed in E. coli and purified 24-fold to about 98% homogeneity by chromatography on hydroxylapatite and Q-Sepharose. On the basis of the comparison of the elution profile for enzyme activities upon gel permeation chromatography (Sephacryl S-400) with the molecular weight of 80,000 determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, the fusion enzyme appears to exist in monomeric, dimeric, and tetrameric forms, all of which exhibit both enzymatic activities. The Km values of the fusion enzyme for substrates were similar to those for the corresponding native enzymes, except for UDP-glucose, but the kcat values were smaller than those for the native enzymes. The fusion enzyme shows kinetic advantages in that the initial velocity to produce glucose-1-P from UDP-galactose and galactose-1-P is about 20% faster than that for a mixture of equal activities of the separate enzymes. PMID- 7873671 TI - Synthesis and properties of cholesteryl-modified triple-helix forming oligonucleotides containing a triglycyl linker. AB - In order to enhance the nuclear uptake of triple-helix forming oligonucleotides (TFOs), a triglycylcholesterol group was attached to the 3' end. The peptide unit was introduced as a "labile" linker with the aim of releasing the oligonucleotide from the endosomes by the action of peptidases after crossing the cell membrane. Cholesteryl-CPG (8) and -TentaGel (9) supports containing 2-[N (glycylglycylglycyl)amino]propane-1,3-diol (GAP-3) linker were prepared and used for automated oligonucleotide synthesis. The synthesis, characterization, and stability of these compounds are described. PMID- 7873672 TI - [Nucleotide sequence of the Escherichia coli B38 flagellin gene]. AB - The fliC gene of the E. coli B38 flagellin has been cloned and its nucleotide sequence determined using the terminator method. According to the sequencing data, the flagellin contains 565 amino acid residues which exceeds by 65 residues the number of amino acid residues in the earlier decoded E. coli K12 flagellin. Strong homology was observed in the two flagellins among the 160 initial and 89 tail-ended residues, whereas the central, variable parts showed no homology. Similar to the K12 flagellin, the B38 flagellin has no serines, cysteines or tryptophans. The variable part of the fliC E. coli B38 gene contains a Chi-site which initiates the genetic recombination in E. coli and related species. PMID- 7873673 TI - [Participation of the quinone acceptor in the transition of complex I from an inactive to active state]. AB - Almost complete slow activation of the deactivated purified Complex I was observed after the steady-state NADH: cytochrome c reductase reaction turnovers catalyzed by the endogenous (tightly-bound) ubiquinone and contaminant Complex III. The rotenone-sensitive NADH oxidase was reconstituted from bovine heart Complex I and Escherichia coli quinol-oxidase. The ratio between active and inactive Complex I during the steady-state NADH oxidase reaction catalyzed by the reconstituted system was shown to be proportional to the rate of quinol oxidation. Analogous result was obtained for the NADH oxidase reaction catalyzed by the submitochondrial particles. It is concluded that the ratio between active and inactive Complex I depends on the quinone redox state. One of the functions of ubiquinone-binding site(s) in Complex I is the control of its active/inactive state. PMID- 7873674 TI - [Enzymatic activity of the nuclear matrix]. AB - The scope of the review is to illustrate the great diversity of enzymatic activities bound to the nuclear matrix. These data are usually summarized in terms of replication, transcription, DNA repair, etc. Such an approach is understandable; however, the great diversity of enzymes is thereby obscured. The review presents the data on enzymatic activities according to the International Enzyme Classification (EC) with the main emphasis on the enzymological aspects of the phenomena described. The enzymes represent almost all classes of enzymes discovered in the nuclear matrix: oxidoreductases, transferases, hydrolases, isomerases and ligases. The presence of ligases is supposed. Nuclear matrix enzymes form functional systems which provide the replication, transcription and regulation of gene expression, DNA repair, transduction of signals by the secondary messengers, antiviral defence, maintenance and modification of the nuclear matrix structure and recombination. PMID- 7873675 TI - [A prosegment of the yeast alpha-factor controls a heterologous protein (human growth factor) in Saccharomyces cerevisiae culture media]. AB - The role of the yeast pheromone prosegment--alpha-factor--in the export of the heterologous protein, the human growth hormone (hGH), in the culture medium of S. cerevisiae has been studied. Using genetic engineering constructions, it has been shown that different N-terminal signal peptides (SP) are not able to provide the hGH export. Transformant cells carrying the plasmid with a hybrid sequence encoding the prosegment-hGH (without SP) accumulate non-glycosylated pro-hGH in the cytosol. Only the combination of SP and the prosegment as the N-terminal fragment of the hGH precursor results in the processing and export of the mature form of the hormone. The origin (or type) of SP is of no significance. The glycosylation inhibitors--2-deoxy-D-glucose and tunicamycin--suppress the export but not the entry of hGH into the periplasm, thus indicating a critical role of the intactness of the prosegment polymannose chains for the efficient export of heterologous protein. A conclusion is drawn that the two preprosegment parts play different roles. The SP constituent of prepro-hGH introduces pro-GH into the general secretory pathway, while the prosegment resulting from the SP cleavage directs hGH from the cell into the culture medium. PMID- 7873676 TI - [Inhibition of human platelet aggregation by a new class of soluble guanylate cyclase inhibitor, generating nitric oxide]. AB - Diacetidine-di-N-oxide derivatives have been found to be capable of generating nitric oxide (NO) non-enzymatically, via an entirely new mechanism--NO splitting at physiological pH. The effects of the synthesized compounds on the human platelet soluble guanylate cyclase activity and ADP-induced human platelet aggregation have been investigated. Four out of seven derivatives tested exhibited a distinct correlation between the intensity of platelet guanylate cyclase activation, inhibition of platelet aggregation and acceleration of their disaggregation. The ability of the compounds to be decomposed under the given experimental conditions with NO formation and the observed correlation between the amount of the NO formed and the intensity of guanylate cyclase activation suggest that the NO-dependent mechanism of guanylate cyclase activation and the intraplatelet cGMP accumulation are responsible for the antiaggregating/disaggregating properties of the compounds used. The data obtained suggest that 1.2-diacetidine-di-N-oxide derivatives may be regarded as antiaggregating agents of a new class. PMID- 7873677 TI - [Study of the rotational mobility of E1- and E2- conformers of Ca-ATPase in sarcoplasmic reticulum membranes using a time-resolved phosphorescence anisotropy method]. AB - Membrane preparations of sarcoplasmic reticulum Ca-ATPase from rabbit skeletal muscles were covalently labelled with eosin-5'-isothiocyanate at Lys 515 residue in a putative active site and with 4-(iodoacetamido)-eosin (presumably, at Cys 670 and Cys 674 residues). These preparations were used to measure the laser flash induced phosphorescence anisotropy in a microsecond time scale. An analysis of effects of diethyl ether, glycerol, the nonionic detergent C12E9 and Ca-ATPase ligands stabilizing the enzyme in the E2 or E1 conformeric state, on the anisotropy parameters showed that Ca-ATPase of sarcoplasmic reticulum membranes is present in both monomeric and oligomeric states. The enzyme transition from the E1 to the E2 conformation is due to the increase in the content of oligomeric complexes and their average size. These data support the hypothesis that the oligomeric state of Ca-ATPase can be changed during enzyme reaction cycle. PMID- 7873678 TI - [Determination of solvent accessibility of residues of aromatic amino acids in proteins using the second derivative of the UV-absorption spectrum]. AB - A new method for determining the solvent accessibility of tyrosine and tryptophan residues in proteins from the wavelengths of absorption peak maxima in secondary derivatives of UV absorption spectra has been developed. Analytical expressions for calculating the number of groups in latent and exposed states of amino acid residues in protein globules were obtained on the basis of the previously elaborated mathematical model of spectral changes observed during the transition between those respective states. The new procedure was used to analyze sixteen proteins and showed a good correlation between the experimental results and literary data. PMID- 7873679 TI - [A new site specific endonuclease-methylase from a thermophilic strain of Bacillus species LU11]. AB - A new site-specific endonuclease BspLU11III was purified to homogeneity from a thermophilic strain Bacillus species LU11. BspLU11III recognizes the 5'-GGGAC-3' sequence on the double-stranded DNA and cleaves the 10/14 and 11/15 nucleotides in different strands away from the recognition site. The enzyme exists in solution as a monomer with a molecular mass of about 93 kDa. When incubated with S-adenosyl-L-methionine, BspLU11III displays a DNA-methyltransferase activity. The adenine residue is methylated inside the recognition site 5'-GGGAC-3' in the only strand. The restriction activity does not change in the presence of ATP but is stimulated by 80 microM S-adenosyl-L-methionine (4-fold). Magnesium cations are needed for the restriction activity. Sodium chloride stimulates the "star" activity of BspLU11III. According to its properties, BspLU11III can be classified as a type IV endonuclease. PMID- 7873680 TI - [A new site-specific endonuclease and methylase from a thermophilic strain of Bacillus species KT6]. AB - The site-specific endonuclease R.BspKT6I and the cognate site-specific methylase M.BspKT6I have been isolated from the thermophilic strain of Bacillus species KT6 using gel-filtration on Sephadex G100 followed by chromatography on heparin Sepharose and hydroxyapatite. Endonuclease BspKT6I is an isomer but not an isoschizomer of Sau3AI and MboI. It recognized on the DNA molecule the GAT decreases C sequence and cleaves it; however, unlike Sau3AI and MboI it produces 3'-protruding dinucleotides. The site cleavage is inhibited by dam-methylation. The sticky ends resulting from the BspKT6I cleavage are identical and complementary to the ends formed after the PvuI cleavage. The isolated from the B. species KT6 methylase protects the DNA from subsequent cleavage by BspKT6I. Adenine is a methylated base. PMID- 7873681 TI - [Inhibition of elastin hydrolysis, catalyzed by human leukocyte elastase and cathepsin G, by the Bowman-Birk type soy inhibitor]. AB - Cathepsin G stimulates the hydrolysis of elastin from bovine neck ligament catalyzed by human leukocyte elastase. Stimulation factor depends on the ratio of the enzyme concentrations and ionic strength and equals 1.0-2.0. The classical Bowman-Birk inhibitor from soya retards strongly the hydrolysis of elastin catalyzed by leukocyte elastase, cathepsin G and the mixture of both. The inhibitory effect is practically unaffected by the adsorption of the enzymes on elastin, prolongation of the enzymatic reaction and ionic strength. PMID- 7873682 TI - [Correlation of DNA degradation, induced by tumor necrosis factor-alpha, with accumulation of sphingosine in the nucleus and peroxides in DNA]. AB - The tumour necrosis factor alpha (TNF-alpha) initiates DNA degradation in many types of cells, eventually resulting in a programmed cell death (apoptosis). In order to study the mechanism of TNF-alpha action in vivo, the dynamics of mouse liver DNA fragmentation was examined after intraperitoneal administration of recombinant hTNF-alpha (10 and 40 micrograms per animal). The number of single strand (SSB) and double-strand (DSB) breaks was determined electrophoretically and interruption of hydrogen bonds (secondary structure defects SSD) were studied by the kinetic formaldehyde method. In parallel experiments the accumulation of peroxide products in DNA, the activity of sphingomyelinase and the content of sphingosine in liver cell nuclei were measured. Sphingomyelinase activation and sphingosine accumulation in the nuclei were found to coincide in time with the maximal values of DNA degradation parameters (SSB, DBS and SSD). TNF-alpha caused a dose-dependent accumulation in DNA peroxide products which seem to lead to the DNA damages. The role of sphingomyelin cycle products and peroxidation in DNA fragmentation induced by TNF-alpha in vivo is discussed. PMID- 7873683 TI - [Regulation of the cycle of phospholipid turnover in hamster fibroblasts transformed by v-src and N-ras oncogenes]. AB - The phospholipid turnover has been studied in two lines of golden hamster cells: in cells transformed by the Rous sarcoma virus (line HET-SR) and in cells additionally transfected with the activated oncogene N-ras (line HET-SR-N-ras, clone 6). It has been found that HET-SR cells are distinguished by a high level of phosphatidylcholine turnover and a relatively low level of phosphoinositide turnover. Transfection of cells with the activated N-ras (line HET-SR-N-ras) leads to the inhibition of phosphatidylcholine synthesis and activation of phosphoinositide metabolism. Both cell lines preserve their sensitivity to serum growth factors stimulating the rate of phospholipid turnover. In both cell lines dexamethasone decreases the rate of DNA synthesis and inhibits the phosphatidylcholine and phosphoinositide turnover. At the same time, dexamethasone does not influence the predominant activation of phosphatidylcholine synthesis in HET-SR cells or the activation of phosphoinositide synthesis characteristic of HET-SR-N-ras cells. The data obtained suggest that the transmission of the mitogenic signal from growth factor in HET-SR and HET-SR-N-ras cells occurs via the activation of the phospholipid turnover and is controlled by steroid hormones. The role of v-src and N-ras oncogens in the transmission of the mitogenic signal seems to be insignificant; their activity is not controlled by dexamethasone. PMID- 7873684 TI - [Procedure for purifying RNA polymerase II from human placenta]. AB - DNA-dependent RNA polymerase IIB having a specific activity of 320 u./mg has been isolated from the term placenta homogenate using extraction performed at 4-6 degrees C in the presence of 75 mM ammonium sulfate and 1.5% nonidet P40, fractionation on DEAE-cellulose DE 23, desalting and heparin-agarose chromatography, resulting in 330-fold purification and a 18% yield. Technical details have been determined which are of crucial importance for reproducibility of affinity chromatography. The possibility of proteolysis of the IIc subunit during enzyme purification has been demonstrated. PMID- 7873685 TI - [A new form of aspartate aminotransferase crystals]. AB - A new crystal form of chicken cytosolic aspartate aminotransferase (EC 2.6.1.1) has been grown using a mixture of ammonium sulfate with ethanol as a precipitant. Crystals of the enzyme belong to the space group P 2(1)2(1)2(1) having the following unit cell dimensions: a = 62.38 A, b = 117.41 A, c = 124.34 A. There is one molecule of the enzyme in the asymmetric unit. The crystals diffract at 1.8 A resolution. PMID- 7873686 TI - [Equilibrium and kinetic parameters of the interaction of peroxidase and its conjugates with specific antibodies in solution]. AB - Horseradish peroxidase (HRP) and its conjugates with IgG (HRP-IgG) and cortisol (HRP-COR) interactions with polyvalent antibodies against peroxidase (ANTI-HRP) have been studied by homogeneous enzyme immunoassay. The total catalytic activity in o-phenylenediamine oxidation for free peroxidase or its conjugates and their immunocomplexes with antibodies against the enzyme (ANTI-HRP) has been measured. Linearization of time dependencies of the initial rate for peroxidation in the ln (v-v infinity)-time coordinates, where v and v infinity are the reaction rates at a definite moment of time and after the onset of the equilibrium, as well as in the [ANTI-HRP]/(v-v infinity)-[ANTI-HRP]0 and I/[ANTI-HRP]0k1 + k-1)-[ANTI-HRP]0 made it possible to determine the dissociation constant, Kd, and rate constant for the formation and dissociation, for the immunocomplexes k1 and k-1. The Kd values were in good agreement with those determined by the classical Scatchard method. PMID- 7873687 TI - [Characteristics of polyphosphatase activity of Saccharomyces cerevisiae cytosol]. AB - The cytosol fraction purified from cellular organelles was obtained from S. cerevisiae yeast cells. This cytosolic fraction contained a polyphosphatase activity comprising nearly 65% of such in the protoplast homogenate. The pH optimum of this activity was 6.5-7.5. Bivalent metal cations stimulated the polyphosphatase activity 9-14-fold in the following order: Zn2+ > Co2+ > Mg2+, Mn2+. Fe2+, Cu2+ and Ca2+ ions inhibited this activity at all concentrations used. The cytosolic polyphosphatase was effectively inhibited by molybdate and heparin. Heparin was effective only in the presence of Mg2+, Mn2+ and Co2+ but had no effect in the presence of Zn2+. Heparin inhibited polyphosphatase competitively. The polyphosphatase activity was the same with poly (P)9-poly (P)208. On poly (P)9, poly (P)15 and poly (P)208 the Km(app) values were equal to 19, 11, 1.2 microM, respectively. The molecular mass of cytosolic polyphosphatase determined by gel filtration on Sephacryl S-300 was 50 kDa. PMID- 7873688 TI - [1,5-poly(ribitol phosphate) with tetrasaccharide substituents in the cell wall of Agromyces fucosus ssp. Hippuratus]. AB - Cell walls of Agromyces fucosus ssp. hippuratus VKM Ac-1352T and VKM Ac-1353 contain teichoic acids of identical structure. The polymer is of a 1.5 poly(ribitol phosphate) type. Each ribitol phosphate residue is substituted at C 4(2) by tetrasaccharide having the following structure: alpha-L-Rhap(1-->3)-alpha L-Rhap-(1-->3)-beta-D-GlcpNAc-(1-- >2)- alpha-L-Rhap-(1-->. The teichoic acid chain is made up by 12-13 repeating units. No structurally identical polymer of the procaryotic cell wall has so far been reported. PMID- 7873689 TI - [Rotational mobility of membrane-bound Na,K-ATPase]. AB - The rotational mobility of E1 and E2 conformers of duck salt gland Na,K-ATPase labelled with eosine-5'-isothiocyanate (EITC) was studied using a time-resolved phosphorescence anisotropy approach. For each conformer, two types of the rotational mobility were found. The rotational correlation time of the faster component equal to about 15 microseconds at 20 degrees for the both conformers, was ascribed to the rotation of the (alpha beta) protomer with an apparent radius 2.4 nm. The slower component (100-500 microseconds depending on experimental conditions) was suggested to reflect the presence in the bilayer of associates between Na,K-ATPase molecules or those with other protein constituents of the membrane bilayer. A rise in temperature tends to decrease the fast component with a subsequent increase in the slow component of the experimental curve, apparently due to oligomerisation of the protomers into oligomers. The size of the oligomers depends on pH and temperature and under favourable conditions may come up to octamers. PMID- 7873690 TI - [Decrease in the intracellular concentration of O2 as a special function of the cellular respiratory system]. AB - A hypothesis is put forward assuming that uncoupled or non-coupled respiration is functioning as a mechanism lowering intracellular [O2] and preventing thereby non enzymatic one-electron reduction of O2 to O2.-. A study of effects of some analogs of thyroid and steroid hormones on mitochondria suggests that the former may operate as uncoupler, the later being its antagonist. It is suggested that non-specific pore in mitochondria can also be involved in the same function. PMID- 7873691 TI - Respiratory abnormalities in infants of substance-abusing mothers: role of prematurity. AB - It is a current hypothesis that maternal history of drug addiction during pregnancy and detection of drugs in the urine of the newborn are associated with increased incidence of apnea. To test this hypothesis, we reviewed polygraphic studies of respiration in two groups of infants who had been exposed in utero to cocaine (and other drugs). The first group was composed of 20 term infants (39.1 +/- 0.8 weeks gestation), and premature infants (35.4 +/- 0.8 weeks gestation). None of the infants were on methylxanthines. These infants were matched with 15 term and 15 preterm infants of similar gestational age. Variables studied were: heart rate, respiration, chest impedance pneumography, nasal airflow and oxygen saturation (pulse oximetry). Apnea indices for central and obstructive events of short and long duration as well as periodic breathing and oxygen saturation were obtained. Term drug-exposed infants had less central apnea and a higher rate of periodic breathing compared to term controls, whereas drug-exposed premature infants had more obstructive apnea and less periodic breathing compared to premature controls. These observed differences within groups were subtle and clinically insignificant. Other parameters studied were not different. When term and preterm infants were compared, preterm infants had significantly higher central apnea, obstructive apnea and periodic breathing rates. These differences appeared to be related to gestational age differences, not to drug exposure. There was no evidence that exposure to cocaine and other drugs actually inhibited respiration. PMID- 7873693 TI - Plasma chromium levels in hypoglycemic preterm, full-term and in intrauterine growth-retarded babies. AB - Serum chromium levels of hypoglycemic preterm and full-term babies were investigated. Normoglycemic preterm and full-term babies were selected as the control group. There was no statistically significant difference in serum Cr levels between preterm and full-term, hypoglycemic and normoglycemic, preterm hypoglycemic and preterm normoglycemic, full-term hypoglycemic and full-term normoglycemic babies. Serum Cr levels of intrauterine-growth-retarded babies were relatively low compared to infants appropriate for gestational age. Serum Cr levels of babies with mothers younger than 35 years of age had significantly lower levels than older mothers' babies. PMID- 7873692 TI - Cocaine exacerbates hypoxia-induced cell damage in the developing brain: effects on ornithine decarboxylase activity and protein synthesis. AB - The immature brain is resistant to cell damage from hypoxia, such as that experienced during parturition. Because cocaine causes cerebral ischemia, we examined whether cocaine interferes with this resistance. On postnatal days 1, 4 or 8, neonatal rats were given an acute injection of saline or cocaine (30 mg/kg s.c.) and were then exposed to 7% O2 for 2 h. At the end of the exposure period, activity of ornithine decarboxylase (ODC), an enzymatic marker for activation of cell damage/repair, was assessed in different brain regions. Across all ages and regions, cocaine by itself suppressed ODC, reflecting reduced cell metabolism in the face of ischemia; the protein synthetic rate, assessed with [3H]leucine incorporation, was largely preserved during the drug insult. On postnatal day 1, hypoxia alone also led to a reduction in forebrain ODC as part of the protective metabolic response, with preservation of protein synthesis despite restricted oxygen availability. However, when cocaine and hypoxia were combined, ODC was induced and protein synthesis fell, indicating the onset of cell damage. By 4 days of age, brain maturation produced a change in the metabolic response to hypoxia alone, characterized by ODC induction; when cocaine was present, the response to hypoxia was exacerbated. At 8 days of age, neonatal brain again showed ODC induction with hypoxia, but in this case, cocaine pretreatment reduced the effect on ODC. Measurements of the patterns of protein synthesis during and after hypoxia indicated that cocaine pretreatment was enhancing the cell damage component of the response (increased protein synthesis during hypoxia) and reducing the cell repair component (decreased ability to induce ODC). In contrast to the interaction of acute cocaine with hypoxia, chronic prenatal treatment with cocaine did not elicit exacerbation of the cell damage markers during a subsequent exposure to postnatal hypoxia; worsening of hypoxic cell injury thus occurs only when cocaine is present concurrently with the hypoxia, as would be expected from direct ischemic actions of cocaine. Enhanced sensitivity to hypoxia induced brain cell damage could be an important contributing factor to the net effects of cocaine on brain development in light of the acute ischemia associated with 'crack' cocaine smoking, hypoxia/ischemia from cigarette smoking, or hypoxia during parturition. PMID- 7873694 TI - Dose-effect relationship of bilirubin on striatal synaptosomes in rats. AB - The uptake of tyrosine as precursor of dopamine in striatal nerve endings was studied in rat striatal synaptosomes to evaluate the role of different bilirubin concentrations on this mechanism of synaptic neurotransmission. Freshly prepared striatal synaptosomes obtained from adult male Sprague-Dawley rats (200-300 g) were homogenized in about 25 vol of 0.32 M sucrose and 5 nM Hepes at pH 7.4 and centrifugated at 12,000-16,000 rpm for 20 min. 14C tyrosine was evaporated under N2 and resuspended in tyrosine 100 microliters/ml. Different concentrations of crystalline bilirubin ranging from 70 to 140 microM at 10-min intervals were prepared. Eighty microliters of synaptosomes were added to 5 microliters of the different bilirubin concentrations and 20 microliters of 14C tyrosine. The results of this study show a statistically significant correlation between bilirubin levels and tyrosine uptake in rat synaptosomes (p < 0.05) supporting the hypothesis that the effect of bilirubin on neuronal excitability is dose dependent. PMID- 7873695 TI - Maturation of A71915-dependent inhibition of atrial natriuretic peptide stimulated cyclic GMP production in isolated rat glomeruli. AB - Atrial natriuretic peptide (ANP) regulates glomerular hemodynamics by interaction with biologic receptors (GC-A/ANP) that possess particulate guanylyl cyclase activity. In a previous study we have shown a developmental difference in glomerular response to ANP where preweaned glomeruli produced significantly less extracellular cGMP in response to ANP. Because of the possibility that functional differences in the ANP biologic receptor might exist during development, further characterization of GC-A/ANP receptor response in glomeruli of developing rats was done using a structural analogue of ANP. A71915 (Abbott Laboratories) is a structural analogue of ANP which has been shown to inhibit activation of ANP receptor-associated guanylyl cyclase in vascular smooth muscle cells. The purpose of this study was to investigate the ability of A71915 to inhibit ANP-stimulated cGMP response in isolated glomeruli of adult and preweaned rats. Isolated glomeruli from preweaned or adult rat kidneys were preincubated for 15 min with A71915 (10(-5) M) prior to addition of ANP (up to 10(-6) M). Glomerular response of production of intracellular and extracellular cGMP was measured by radioimmunoassay. Adult glomeruli produced significantly greater amounts of extracellular cGMP compared to preweaned glomeruli for concentrations of ANP > or = 10(-9) M. Infant glomeruli had a significant decrease in the production of ANP stimulated intracellular cGMP in the presence of A71915 (10(-5) M), whereas extracellular cGMP production was unchanged. In contrast both ANP-stimulated intracellular and extracellular cGMP were significantly decreased by A71915 in adult glomeruli. These results demonstrate the maturation of the glomerular response to ANP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873696 TI - Copper distribution in fetus and placenta of the macular mutant mouse as a model of Menkes kinky hair disease. AB - Menkes kinky hair disease (MKHD) in humans is caused by a disturbance in copper homeostasis. A mutant mouse shows clinical and biochemical features very close to MKHD. In an attempt to elucidate the defect in copper transport, the copper distribution in various organs of 18-gestational-day-old macular mouse embryos, following administration by a single injection of saline (control) or 50 micrograms of CuCl2 on day 16 of gestation or by two injections on days 15 and 17 of gestation to the dams, was examined both biochemically and histochemically. The copper content in the hemizygous fetus (Ml/y) born to the homozygous mother, who had no copper injection during gestation, was lower in the brain and liver but higher in the placenta than in the respective organs of the normal fetus. When 50 micrograms of CuCl2 was injected into heterozygous dams (Ml/+) on day 16 of gestation, their hemizygous fetuses showed a slight increase in the copper content in the brain and liver, but the amount of copper in these organs was still less than that of the normal fetus. Conversely, the copper content in the placenta of the hemizygous fetus was far higher than that of the normal fetus. In the copper staining of the fetuses harvested from heterozygous dams, some fetuses showed copper deposition in the placenta, but not in the liver. The others showed no copper deposit in both the placenta and liver, thus indicating that the former were hemizygous for the mutation and the latter were normal littermates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873697 TI - Salience of fear/threat in the affective modulation of the human startle blink. AB - Affective valence modulates the magnitude of the human startle blink such that blinks are reduced by positive affect and enhanced by negative affect. Do different negative contents similarly potentiate startle? Our first study compared the effects of slides selected to depict positive, neutral, frightening, or disgusting scenes. Blink magnitude was significantly facilitated during frightening pictures and attenuated during positive pictures, but blinks during disgusting pictures did not differ from the neutral condition. Replicating previous work, skin conductance magnitude and baseline EMG activity were greater during affective than neutral scenes. In an additional group of 12 subjects, both reaction times for whether slide content was positive or negative and subsequent picture recall were similar for frightening and disgusting pictures. A follow-up study replicated the blink results for subjects who viewed the same picture set and for subjects who viewed only positive, neutral, and disgusting pictures. These results suggest that scenes depicting fear or threat may be especially salient in the affective augmentation of human startle. PMID- 7873698 TI - Brief interval heart period variability by different methods of analysis correlates highly with 24 h analyses in normals. AB - Heart period variability (HPV) measured from 24 h ECG recordings predicts mortality following myocardial infarction and may be a measure of cardiovascular health in the general population. Since epidemiologic evaluation of healthy people will require alternatives less intensive than 24 h recording, we investigated the relationship between HPV derived from 24 h and 5 min recordings, using two approaches for obtaining RR intervals. Template-matching (TM) algorithms were applied to 24 h ECG recordings from 41 normal subjects (mean age 35.7 +/- 13 years). Five min of ECG data during this 24 h period also were collected by an on-line microcomputer-based system for peak detection (PD) analysis. Intraclass correlations comparing the TM and PD approaches on the 5 min period were .80 or greater for all measures of HPV. Pearson correlation coefficients between the 5 min (TM) estimates and 24 h data and 5 min (PD) estimates and 24 h data exceeded .60 and .55, respectively, for all but one variable, with all p values < .05. Thus, in healthy adults, TM and PD approaches to HPV estimation from short segments of ECG data are highly consistent and the correlations between HPV obtained from brief intervals and 24 h measures were substantial, suggesting that assessment of HPV as a screening measure of cardiac autonomic control in healthy adults may be feasible. PMID- 7873699 TI - Conditioned manipulation of natural killer (NK) cells in humans using a discriminative learning protocol. AB - There is growing evidence indicating that the immune function can be modified by classical conditioning techniques. This phenomenon, initially explored in animals, is further documented by studies providing evidence that the human immune response can also be influenced by classical conditioning processes. In the present study, we tested the hypothesis that human immune parameters can be modulated by discriminative learning processes. Using a classical discriminative conditioning design, healthy volunteers were provided with a CS+ (sherbet sweet/white noise), which was repeatedly paired with an injection of epinephrine (unconditioned stimulus, US). After epinephrine injections (0.2 mg subcutaneously), a transient increase of natural killer (NK) cell activity (unconditioned response, UR) could be observed. A second stimulus complex (herbal sweet/auditory stimulus, conditioned stimulus, CS-) remained without reinforcement. After repeated presentation of the stimuli, re-exposure of the CS+ on the test trial 1 resulted in a significantly increased number of NK positive (NK+) cells and in slightly elevated NK cell activity. No alteration of NK cells, however, could be observed after presentation of the CS-. A second re-exposure of the CS+ on test trial 3, again resulted in a marked increase of NK+ cell number as well as in significantly elevated NK cell activity. The data presented here extend previous observations of conditioned alteration of immune responses in humans and indicate that the human organism might be able to react differentially to external stimuli, which have been associated with different immunological consequences. PMID- 7873700 TI - Temporal integration of auditory information in sensory memory as reflected by the mismatch negativity. AB - Event-related potentials (ERPs) to different types of infrequent change in a tone pair composed of two closely spaced tones of different frequencies were recorded. The mismatch negativity (MMN), a change-specific component of the ERP, was elicited by reversing the order of the two tones, by repeating the first tone, by replacing the first tone with the second tone, or by omitting the second tone. The omission of the second tone, however, elicited the MMN only when the interval between the two tones was very short (offset to onset 40 or 140 ms) but did not when this interval was somewhat longer (240 or 340 ms). The pattern of the present results suggests that sensory-memory traces, as reflected by the MMN, integrate information about two closely spaced stimuli into a unitary sensory event. PMID- 7873701 TI - Contingent negative variation (CNV) and erotic preference in self-declared homosexuals and in child sex offenders. AB - Contingent negative variation (CNV) was recorded bilaterally from central electrodes using a "match/mismatch" paradigm in (Study 1) samples of heterosexual men (N = 6), gay men (N = 10) and lesbian women (N = 14) and (Study 2) in samples of child sex offenders (N = 34) and heterosexual control men (N = 19). Sexual orientation was assessed using the Multidimensional Scale of Sexuality (MSS) and the Human Sexuality Questionnaire (HSQ). Separate CNV averages were formed for each condition of stimulation: for Study 1, slides of adult male and female nudes; for Study 2, slides of child, pubescent and adult male and female nudes. Penile plethysmographic (PPG) data were also obtained from 15 of the child sex offender sample while they viewed stimuli of the same categories as were used in the CNV recording. On the basis of their PPG responses to children, child sex offenders were classified as either "pedophiles" or "non-pedophiles". In Study 1 significant Group x Sex (of slide) and Group x Electrode interactions indicated that: (i) heterosexual men (but neither homosexual group) showed significantly larger CNVs to female than to male slides; (ii) both homosexual groups showed significantly asymmetrical (R > L) CNVs. In Study 2, controls showed significantly greater CNVs to adult females than to both adult males and female children. Child sex offenders showed no significant differences in CNV to male and female slides for any age. "Non-pedophiles" showed significantly larger CNVs to female adults than to female children, but "pedophiles" did not. It is concluded that CNV has promise as a measure of both deviant and non-deviant sexual preference. PMID- 7873702 TI - Patterns of cortical electrophysiology and autonomic activity in adults' shyness and sociability. AB - We examined differences in brain electrical activity (EEG), heart rate (EKG), heart rate variability, and behavior among 40 young women who were selected for high (HI) and low (LO) self-ratings of shyness and sociability. EEG and EKG were continuously recorded for 6 min from each subject, just prior to an expected novel social encounter. Each subject was also observed unobtrusively for 5 min during the social encounter. Analyses indicated that the pattern of frontal EEG asymmetry was related to sociability, but not to shyness. LOSOCIABLE subjects displayed greater relative right mid-frontal activation while HISOCIABLE subjects displayed greater relative left mid-frontal activation. A significant shy x sociable interaction was found for parietal asymmetry and for measures of heart rate and heart rate variability. LOSHY/HISOCIABLE subjects displayed greater relative right parietal activation while LOSHY/LOSOCIABLE subjects displayed greater relative left parietal activation. And HISHY/HISOCIABLE subjects displayed a significantly higher and more stable (less variable) heart rate than HISHY/LOSOCIABLE and LOSHY/HISOCIABLE subjects. Analyses also indicated that LOSOCIABLE subjects displayed significantly more signs of nonverbal social avoidance as compared with HISOCIABLE subjects. The present findings suggest that shyness and sociability may be subserved by different neurophysiological systems. PMID- 7873703 TI - Task decision difficulty: effects on ERPs in a same-different letter classification task. AB - A "same-different" letter pair choice reaction time task was used to compare reaction time, performance accuracy, and P3 amplitude and latency at three levels of task difficulty. Stimulus set was held constant across tasks, and task difficulty was manipulated by instructions to the subject. Subjects delivered a button-press response to designate whether members of each letter pair matched or mismatched on the basis of their physical identity (low difficulty), name identity (medium difficulty), or category identity (vowels/consonants, high difficulty). Task decision difficulty was confirmed by slower reaction times and reduced response accuracy. P3 amplitude was inversely related to task decision difficulty; relatively larger P3s were associated with matched (vs. mismatched) letter pairs. These findings evidence direct effects of task difficulty on P3 amplitude, possibly as the result of "equivocation" related to more difficult task judgments. PMID- 7873704 TI - Social and emotional functions in facial expression and communication: the readout hypothesis. AB - Fridlund (Fridlund, A.J. (1991). Biological Psychology, 32, 3-100) has argued that facial displays are specific to intent and context, rather than being readouts of underlying motivational-emotional states. This paper responds that these views are not incompatible, and that subjective emotional experience functions in part to enhance the learned control of emotional expression and communication. It summarizes the readout position, answers Fridlund's criticisms identifying it with the different notion of "spillover," and contends that the expressive readout functions in spontaneous communication. Fridlund's assertions that the readout is a reflex-like process, and that the readout view has ignored the receiver's coevolutionary role in communication, are addressed. Evidence supporting the readout view is presented, including studies suggesting that there are hierarchically organized neurochemical systems underlying subjective, expressive, and peripheral physiological responses. Such primary motivational emotional systems (primes) are basic to the readout theory. PMID- 7873705 TI - Modulation of aortic and cardiac G protein alpha subunits and their mRNAs during norepinephrine infusion in rats. AB - These studies examine the possibility that alterations in the expression of G protein alpha subunits occur during desensitization of adrenergic responses in the cardiovascular system. To desensitize adrenergic receptors, rats were infused with norepinephrine (NE) subcutaneously (0.1 mg/kg/h) for 3 or 6 days using osmotic minipumps. G protein alpha subunits and their mRNAs were then measured in the aorta and heart using selective antibodies and cDNA probes. Infusion of NE for 6 days significantly decreases the levels of Gs alpha, Gi alpha and Go alpha in the aorta. The mRNAs for the alpha subunits are not altered in the aorta after NE infusion for 3 or 6 days indicating that reduced mRNA expression does not account for the decreased proteins. In the atrium and ventricle the levels of Gs alpha decrease after NE infusion for 3 days but then return to control levels by day 6. The levels of atrial and ventricular Gi alpha are unaltered after NE infusion for 3 days but increase significantly by day 6. Go alpha levels do not change in the atrium or ventricle on either day. The level of Gi2 alpha mRNA increases after NE infusion for 6 days and may account for the increased alpha i protein. The levels of the other G alpha mRNAs do not change in the atrium or ventricle. These results demonstrate that expression of G protein alpha subunits is altered during cardiovascular desensitization, raising the possibility that modulation of the alpha subunits may contribute to reduced adrenergic responsiveness. PMID- 7873706 TI - The pharmacology of human blood vessels in vivo. AB - Forearm plethysmography coupled with brachial artery drug administration and the Aellig technique in hand veins coupled with local venous drug administration are both extremely powerful tools, now widely available to the clinical pharmacologist. These techniques allow precise assessment of drug effects on vascular smooth muscle in vivo, without the confounding influences of drug effects on other organs or activation of neurohumoral reflexes. These local techniques allow the direct study of human vascular physiology, pharmacology, and pathophysiology in vivo in humans. In addition, they can form an important part of the early clinical development programme for new cardiovascular drugs, including drugs affecting the renin-angiotensin system and the sympathetic nervous system, as well as the novel agents arising from research on the vascular endothelium. Given the power of these techniques, it is important to consider where studies in patient volunteers might answer particular questions better than experiments in animal models of disease. PMID- 7873707 TI - Phosphocreatine and creatine kinase in energetic metabolism of the porcine carotid artery. AB - OBJECTIVES: Magnetization exchange experiments and force analysis were performed on porcine carotid arteries with varied phosphocreatine (PCr) levels. The aim of these experiments was to determine the creatine kinase (CK) kinetics and the role in hypoxic relaxation. METHODS: The magnetization exchange techniques used were multisite saturation transfer (MST) and conventional saturation transfer (CST). The two techniques were used because CST assumes a two-site exchange while MST allows one to assume a three-site exchange. Mechanical parameters of tension generation and relaxation were measured to determine the energetic effects on contractility of carotid strips. RESULTS: Measurements of molecular exchange between ATP and PCr found the pseudo first-order rate constant (kf) of 0.17 +/- 0.04 S-1 (PCr-->ATP) and kr = 0.12 +/- 0.03 S-1 (ATP-->PCr) in unstimulated porcine carotid artery. In the carotids, despite increased PCr and K+ stimulation, no magnetization exchange is observable with MST. This result indicates that the ATPase was less than 0.04 mumol/g/s (below the NMR resolution) while CK was 0.11 mumol/g/s. Creatine-loaded carotids showed no significant differences in force measurements: maximal force, resting tension, and the rate of hypoxia were all unchanged. CONCLUSIONS: The flux ratio (flux forward over flux reverse) was 0.94 +/- 0.13 which was considered to be indicative of CK being at equilibrium in the resting porcine carotid artery. The rate of the CK reaction is rapid enough to assume a two-site kinetic exchange not limiting energetic supply during hypoxia-induced relaxation. PMID- 7873709 TI - Magnitude of flow-induced contraction and associated calcium influx in the rabbit facial vein is dependent upon the level of extracellular sodium. AB - Intraluminal flow can cause both dilation or constriction of small arteries, depending on the level of tone. Both responses are specifically modulated in the same way by small changes in extracellular Na+ ([Na+]e). We have investigated the effect of changes in [Na+]e on the level of contraction induced by a standard flow of physiological salt solution in ring of segments of the rabbit facial vein and on the associated 45Ca2+ influx and net uptake. Decreasing [Na+]e by 20% reduced the response to flow by 58%, and increasing it by 20% augmented the flow response by the same extent. There is a linear relationship between the level of the flow-induced contraction and [Na+]e over the range 120-180 mM. An alteration in [Na+]e of 10 mM corresponds to a 20% change in flow-induced contraction. This relationship is quantitatively the same as that previously reported for the rabbit ear resistance artery [10]. Histamine (1 microM)-induced tone was not affected by changes in [Na+]e within the range 75-180 mM. 45Ca2+ influx and net uptake per unit force developed in response to flow were unaffected by these changes in [Na+]e. The flow-induced contraction of the vein was selectively, in comparison to that due to histamine, attenuated by amiloride, methyl-isobutyl amiloride and monensin. It is argued that the observation that flow-induced contraction, caused by small alterations in extracellular sodium concentration, is not associated with changes in calcium uptake per unit force is consistent with an extracellular flow sensor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873708 TI - Physiologic responses of REVC, a continuous rabbit endothelial vascular cell. AB - Endothelial cells (EC) are fastidious in their growth requirements in vitro and will not survive extensive passages. We have partially characterized a continuous cell line (> 40 passages) established in culture from New Zealand White rabbit vena cava endothelium (REVC). REVC cells resemble typical EC, but remain hardy when grown on uncoated plastic in DMEM/F12 + 10% FBS. REVC cells have typical cobblestone appearance, are contact-inhibited in monolayers and express factor VIII-related antigen. Weibel-Palade bodies were not seen by electron microscopy. REVC cells grown in 2% FBS on plastic demonstrate dose-dependent increases in [3H]thymidine uptake in response to acidic FGF (10-100 ng/ml), basic FGF (3-100 ng/ml), EGF (10-50 ng/ml), and ECGS (10-100 micrograms/ml). Heparin (5-100 micrograms/ml) potentiates proliferation induced by aFGF and lowered the ED50 for aFGF. REVC cells did not show an increased proliferative rate in response to vascular endothelial growth factor. Transforming growth factor beta 1 and beta 2 profoundly inhibited thymidine uptake at doses as low as 100 pg/ml. When grown on a collagen I substratum, REVC cells became larger, more polygonal and assumed a sheet-like appearance upon reaching confluence. REVC cells plated on fibronectin, laminin or poly-L-lysine demonstrated increases in pericellular granularity and pronounced spreading, especially on fibronectin. Phorbol myristate acetate produced profound morphological changes characterized by swirling whorls of bipolar cells surrounding patches of polygonal cells and multilayered overgrowth. When plated on EHS (Engelbreth-Holm-Swarm) tumor extracellular matrix (Matrigel), REVC cells became quiescent and underwent morphological changes reminiscent of differentiation with elongated cytoplasmic extensions. Chromosomal examination of REVC cells revealed a normal diploid karyotype (2n = 44). This continuous cell line is undergoing further characterization and may be quite useful in investigating many aspects of endothelial cell biology in vitro. PMID- 7873710 TI - Actions of platelet-activating factor on isolated rabbit basilar artery: modulation by activated polymorphonuclear leukocytes. AB - In segments of rabbit basilar artery (BA) platelet-activating factor (PAF) initiated a concentration-dependent transitory contraction which was unaffected by indomethacin or nordihydroguaiaretic acid (NDGA). N omega-nitro-L-arginine (NLA) did not change the magnitude of PAF-induced contraction, but in the presence of NLA the contraction tended to be more prolonged. In precontracted BA segments, PAF caused a concentration-dependent relaxation which was unaffected by NDGA. Indomethacin and NLA decreased PAF-induced relaxation by 10-30 and 70-90%, respectively; in combination these agents totally eliminated PAF-induced vessel reactions. Treatment of BA segments by rabbit peritoneal polymorphonuclear leukocytes (PMNLs) activated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) for 20 min led to PMNL adhesion to the vascular endothelium and a significant decrease (60-100%) in acetylcholine-induced endothelium-dependent vessel relaxation. After the treatment of BA segments, PAF induced strong, slow, tonic contraction of either non-precontracted or precontracted vessels which was unaffected by indomethacin or NLA. NDGA decreased this contraction by 30-60%. These results indicate that PAF is an endothelium-dependent vasodilator that can also produce an insignificant constrictor effect. However, when the vessels are affected by activated PMNLs, PAF is transformed to a strong vasoconstrictor, presumably due to the generation of as yet unknown vasoconstrictor stimuli resulting from PMNL-endothelium interactions. Under these conditions the PAF induced contraction is partly mediated by 5-lipoxygenase metabolites. PMID- 7873711 TI - Hyperosmolarity enhances smooth muscle contractile responses to phenylephrine and partially impairs nitric oxide production in the rat tail artery. AB - The respective effects of hyperosmolarity caused by impermeant solutes, such as mannitol and sucrose, on the endothelium and smooth muscles cell responses were investigated in the rat tail artery. The vessels, with or without endothelium, were infused and superfused with an isosmolar saline solution, and were repeatedly stimulated with phenylephrine. Superfusing with hyperosmolar fluid (390-420 mosm/l) produced a transient increase in the arterial basal perfusion pressure which peaked after approximately 5 min and then declined within 15 min to a stable nonsignificant value above control values in subsequent experiments. In arteries with functional endothelium, the effect of phenylephrine was about 1.9-fold larger in hyperosmotic medium compared to that in isosmotic medium. In hyperosmotic media the response was still more than twofold enhanced in endothelium-denuded vessels compared to those with endothelium. In the latter, indomethacin (10 microM) had no effect, but N omega-nitro-L-arginine methylester (L-NAME; 30 mumol/l), an inhibitor of NO production, enhanced the response to phenylephrine to reach the same magnitude of response as seen in endothelium denuded arteries. This effect of L-NAME was antagonized by L-arginine. Relaxation induced by the NO donor SIN-1 was unchanged by hyperosmolarity, indicating that the effect of NO was not impaired. It is concluded that, in the rat tail artery, the enhancement in phenylephrine-induced contractions produced in a hyperosmolar solution is due to both an endothelium-independent increase in smooth muscle responses and a moderate decrease in the production of NO, or an NO-like factor, by the endothelium. In spite of this reduction, endothelium-derived NO still plays a major role in attenuating phenylephrine-induced contractions in hyperosmolar medium. PMID- 7873712 TI - Alpha-adrenoceptor responses of an isolated human artery and blood pressure. AB - This cross-sectional study examined responses of the isolated cystic artery to 3 alpha-adrenoceptor agonists and the effects of 2 antagonists in relation to subjects' blood pressures. Potency of the 3 amines studied was: alpha methylnorepinephrine > norepinephrine > phenylephrine. Responses to clonidine were trivial (< 5% of maximum) and remained < 25% of maximum in the presence of subthreshold concentrations of angiotensin II. A weak trend for increased potency of alpha-methylnorepinephrine was noted in arteries of subjects with higher blood pressures (r = 0.268, p = 0.027). There was no relationship between blood pressure and pA2 for yohimbine. The pA2 for prazosin could not be calculated because of a decline in maximal responses but prazosin was clearly more potent than yohimbine. The decline in maximal responses to norepinephrine and phenylephrine after prazosin treatment was related to subjects' diastolic blood pressures (r = -0.400, p = 0.003). There were no significant relationships between these measurements of vascular responsiveness and a family history of hypertension. There were also no significant relationships between these measurements of vascular responsiveness and plasma norepinephrine levels, alpha 2 adrenoceptor binding or platelets of beta 2-adrenoceptor binding of lymphocytes. The major postjunctional alpha-adrenoceptors in this artery are of the alpha 1 type. The data suggest that differences in potency of alpha-adrenoceptor agonists in relation to blood pressure may be due to differences in the alpha 2 adrenoceptor but are not likely due to a difference in binding to the receptor itself.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873713 TI - [Effect of hardness and surface quality of metal cones on fracture load of ceramic ball heads of hip endoprostheses]. AB - The safety of ceramic ball heads attached to hip endoprostheses by means of a conical fitting requires that the connection be designed with the ceramic material in mind. The ISO 7206-5 standard describes a static testing protocol to measure the maximal loading limit of the conical connection. In order to achieve high fracture loads in this test, it is necessary to optimize the load-bearing parts of the connection to prevent stress concentrations, to which the ceramic ball is sensitive. For this reason, manufacturers of ceramic balls give their customers specifications for the design of the metal taper, specifying tolerances for angle, roughness, roundness and straightness. In order to investigate which parameters of the metal taper have an influence on the fracture load achievable according to ISO 7206-5, fracture load tests were conducted with zircon oxide (ZIOLOX) heads in combination with test tapers from various manufacturers. The test tapers were made of Ti- or CoCr-based alloys. Before the tests the tapers were completely measured and characterized according to geometric parameters of roughness, roundness, straightness, profile and angle, and physical parameters such as hardness and elastic modulus. Subsequent measurements after the fracture tests characterized changes that occurred in the metal tapers. The fracture loads achieved depended on the potential for deformation of the taper surface. This potential can be described by a factor computed as hardness/roughness. A dependence of the fracture load on elastic modulus, form deviations or taper angle could not be established within the Cerasiv specifications. PMID- 7873714 TI - [Predicting load bearing of the hip joint. Computerized analysis with a 3-D multibody model of the human]. AB - Multibody analysis was applied to construct an advanced model of the human body, where the large joints and complete mass and inertial properties were implemented. The model represents the 50th-percentile rank of a male adult. The hip joint is controlled by three muscle forces. The muscle coordinates were taken from a data source, previously collected by our group. The model enables one to analyze 3D hip joint forces with respect to various joint angles and represents conceptually an improvement of the classical method of graphical statics, which was established by Pauwels [15]. A hip joint load of three times body weight was found in the single leg stance. A load of 3.7 times body weight was calculated when simulating a knee flexion angle of 90 degrees, and a ventral inclination of the resultant hip joint force was seen. A constant amount of gluteus medius muscle force was observed during flexion. An increasing flecting moment at the hip joint, however, had to be balanced by a significantly increased gluteus maximus muscle force. As a consequence, torsional forces can be studied by the system presented here and should also be considered when testing stems of hip prostheses. External muscle and joint forces are provided and can be used as input data for stress analyses. PMID- 7873715 TI - [Value of 3-dimensional emission scintigraphy in evaluating the osseointegration properties of endoprostheses]. AB - The Three-dimensional display of functional images generated by single photon emission computed tomography gives a three-dimensional picture of the bone and the activity of a radionuclide after endoprosthetic joint replacement and allows a judgement of osteoblastic activity concerning bone ingrowth in macroporous surfaces of non-cemented implants. Osteolytic processes can be demonstrated in the same way. PMID- 7873716 TI - [Control system for a complete artificial heart based on a mean value model of the cardiovascular system]. AB - The reliable use of an artificial heart in patients requires a control strategy that is able to monitor and realistically regulate the different loads of the cardiovascular system. The model outlined in the following article was created in an interdisciplinary environment with heart specialists and automation engineers. A control system for an artificial heart, in the form of a peristaltic pump, was created with the help of a load-dependent mean-value model of the cardiovascular system. The resistance of the arterioles in the systemic vascular system RA was chosen as the parameter for the adaptation of the cardiac output. This parameters can be easily and accurately estimated through the measurement of pressures and flows, and it is a very good indicator for the load of the organism. The results, obtained through simulation of the overall system, show a very fast and accurate adaptation of the cardiac output to the needs of the body at changing loads over a large range of workloads. At the same time, the protection of the lungs from excessive pressure is ensured by balance control of the outputs of the two halves of the artificial heart. The control system outlined here needs only pressure and flow sensors, which can be integrated into the pump housing. PMID- 7873717 TI - [Simulation of a one-dimensional impulse transmission along a heart muscle fiber with varied intracellular specific resistance--unidirectional block]. AB - The subject of this study is the modeling of the spread of excitation along a ventricular myocardial fibre based on the one-dimensional "cable" (transmission line) theory. In particular the influence of a varying intracellular c resistivity, R, and of the extracellular potassium concentration [K]o on the propagation is investigated. The membrane model used is the Luo-Rudy model, with which such cellular phenomena as supernormal excitability and Wenckebach pattern can be simulated. The specific resistivity, R, comprises the resistivity of the myoplasm and that of the gap junction. The phenomen of the unidirectional block (UDB) can be simulated in the ischaemic/non-ischaemic transitional zone. Here, the resistivity peak within the ischaemic border zone--caused by collagenous tissue--in combination with a gradient of the R along the fibre-plays a basic role. This simulation study makes it evident that variations in the R-profile have a considerably greater effect on the propagation of a stimulus than variations in the [K]o-profile. PMID- 7873718 TI - Age differences of married and divorcing couples. AB - This paper analyzes the probability of a married couple getting divorced, based on the age difference between the husband and wife. To calculate such probabilities, the distribution of age differences of married couples was derived from the 1991 Census and the 1990 General Social Survey, and the distribution of age differences of divorcing couples was obtained from 1991 divorce data provided by the Department of Justice Canada. These distributions, the first based on data that are seldom available, are also analyzed in this paper. The results provide details about the expected significant imbalances that exist, both for married and divorcing couples, between the number of couples with older husbands and the number with older wives. A model is developed that shows that divorce rates are lowest when the husband is two to ten years older than the wife or when the magnitude of their age difference is extremely large. Furthermore, the chance of divorce is much higher when the wife is older than the husband than vice versa. The demands on a younger spouse--usually the wife--to provide informal health care for an older spouse are briefly discussed. PMID- 7873719 TI - Maternal demographic characteristics and rates of low birth weight in Canada, 1961 to 1990. AB - Vital statistics on live births were used to examine trends in the demographic characteristics of mothers and rates of low birth weight (LBW) (under 2,500 grams) among children born to residents of Canada (excluding Newfoundland) from 1961 to 1990. The total number of live births with known birth weight declined from 458,000 in 1961 to 397,000 in 1990 (-13%). Over those three decades, the number of LBW infants dropped from 33,100 to 22,000 (-34%), and the proportion of live births accounted for by LBW infants (LBW rate) fell from 7.2% in 1961 to 5.5% in 1990 (-24%). An infant's birth weight is related to the mother's health and socio-economic environment. In urban Canada, the LBW rate was about 1.4 times higher in the lowest income neighbourhoods than in the highest. It was also higher among unmarried mothers than their married counterparts (7.3% vs. 5.0% in 1990), and greater among teenage mothers than those aged 20 to 34 (6.7% vs. 5.4% in 1990). The LBW rate was higher among first-borns than second children (6.0% vs. 4.9% in 1990). From 1961 to 1990, the proportion of births occurring outside marriage rose (especially in Quebec), as did the proportion of mothers of "parity 1" (those giving birth to their first child). Conversely, the proportion of births to teenage mothers declined. The LBW rate generally dropped across all maternal demographic characteristics examined, and in every region, over the period studied. The strongest decline was among unmarried mothers (from 11.3% in 1961 to 7.3% in 1990). By region, Quebec had consistently higher LBW rates than the other three regions. However, Quebec's LBW rate declined dramatically between 1961 and 1990, especially among unmarried mothers (from 13.8% to 7.5%). The LBW rate, standardized to the 1961 distribution of maternal age, parity and marital status, declined from 7.2% in 1961 to 5.1% in 1990 (-29%). By 1990, Quebec's standardized LBW rate (5.2%) was very close to the Canadian average (5.1%), while the Maritimes had the highest standardized LBW rate (5.3%). Thus, after standardization there was an almost complete reversal of the regional ranking which had prevailed in 1961. PMID- 7873720 TI - Who goes to the hospital? An investigation of high users of hospital days. AB - Hospital morbidity data are useful for administrative purposes, but because Canadian data are based on the number of hospital visits for a given diagnosis rather than the number of patients with the diagnosis, they have historically been ineffective in determining how many people have been hospitalized with a given condition. Now, by linking computerized patient data, the records of the same patient can be combined. Linked records can be used to estimate disease prevalence, examine health care utilization, and evaluate the effectiveness of medical treatments, procedures and programs. Hospital morbidity records for the fiscal year 1989/90 were linked by person to study hospital utilization in New Brunswick and Saskatchewan. Approximately 11% and 12% of their populations, respectively, were admitted to hospital in the study period. The percentage of the population that was hospitalized increased with age from 50 onwards. About one in four hospital patients were admitted to hospital more than once in 1989/90, and approximately 4% were admitted four or more times. Cancer diagnoses were associated with the highest hospital re-admission rates. About half of hospitalized patients spent five days or less in hospital over the period studied. At the other extreme, 10% of patients, referred to as "high users," accounted for about half of the hospital days--but only 1% of the population in these two provinces. Typically, high users are patients with chronic conditions or illnesses severely affecting cognitive or physical abilities. This profile of high users suggests that high medical costs are due not so much to intensive care of terminally ill patients, but to ordinary medical and palliative care of chronically and seriously ill patients. Restructuring health care data so that all of the records for one patient could be linked would help identify problem areas in the health care system and help evaluate new ways of delivering health care. PMID- 7873721 TI - A look at therapeutic abortions in Canada in 1992. PMID- 7873722 TI - An overview of deaths in Canada in 1992. PMID- 7873723 TI - Highlights on the National Physician Data Base (NPDB). PMID- 7873724 TI - Tuberculosis incidence in Canada in 1992. PMID- 7873725 TI - Structure-function relationships associated with extracellular matrix alterations in diabetic glomerulopathy. AB - Proteinuria and progressive renal insufficiency are the primary manifestations of diabetic nephropathy. Accumulating evidence suggests that these clinical features can be linked, at least in part, to pathologic changes in the glomerular extracellular matrix. Most evidence suggests that glomerular basement membrane thickening and mesangial matrix expansion consist of at least three elements. These are (1) an accumulation of normal extracellular components; (2) an increase in the novel peptide chains of the normal components of Type IV collagen; and (3) an increase in matrix elements not normally expressed in the glomerulus. The pathogenetic features underlying these changes include increased synthesis and decreased degradation of matrix. Abnormal physico-chemical interactions among these matrix elements likely contribute to alterations in three-dimensional structure, leading to proteinuria and loss of glomerular basement membrane filtering surface area. Many of these changes may be explained in whole or in part by direct or secondary effects of hyperglycemia, as well as by hemodynamic changes. PMID- 7873726 TI - Nephrogenic ascites: a poorly understood syndrome. AB - Nephrogenic ascites is a condition characterized by the presence of massive ascites in a patient with ESRD. Neither the exact cause nor the pathogenesis of ascites formation is clearly understood. Patients frequently present with hypertension, moderate to massive ascites, minimal extremity edema, cachexia, and a history of dialysis-associated hypotension. The ascitic fluid is typically an exudate. Although treatment options are limited, continuous ambulatory peritoneal dialysis, peritoneovenous shunt placement, and renal transplantation appear to be effective in controlling ascites formation. Nephrogenic ascites is associated with a grave prognosis, especially if treatment is not instituted. One patient with nephrogenic ascites is described here. PMID- 7873727 TI - Pregnancy outcome and its relationship to progression of renal failure in autosomal dominant polycystic kidney disease. AB - The effect of pregnancy on renal disease has not been defined in autosomal dominant polycystic kidney disease (ADPKD). Therefore, fetal and maternal complication rates in ADPKD women as compared with those in unaffected family members (NADPKD) were assessed. Two hundred thirty-five ADPKD and 108 NADPKD women with 605 and 244 pregnancies, respectively, were studied. Overall, fetal complication rates were similar between ADPKD and NADPKD women (32.6 versus 26.2%). Fetal complications were more common in ADPKD women when they were older than 30 yr. Increased fetal prematurity rates were found in preeclamptic ADPKD women as compared with normotensive ADPKD women (28 versus 10%; P < 0.01). More maternal complications occurred in ADPKD as compared with NADPKD women (35 versus 19%; P < 0.001), with preexisting hypertension being the most important risk factor for a maternal complication to occur. Normotensive ADPKD women who developed preeclampsia were more likely to develop chronic hypertension as compared with those without preeclampsia (89 versus 58%; P < 0.01). Hypertensive ADPKD women with four or more pregnancies had lower creatinine clearances than age-adjusted hypertensive ADPKD women with fewer than four pregnancies (49 +/- 5 versus 66 +/- 3 mL/min per 1.73 m2; P < 0.01). Therefore, normotensive ADPKD women usually have successful, uncomplicated pregnancies. However, hypertensive ADPKD women are at high risk for fetal and maternal complications and measures should be taken to prevent the development of preeclampsia in these women. PMID- 7873728 TI - Hepatic venous outflow obstruction in autosomal dominant polycystic kidney disease. AB - To discuss the clinical presentation, diagnosis, and treatment of hepatic venous outflow obstruction as a complication of polycystic liver disease, four cases diagnosed and treated at our institution have been reviewed and the information from six previously published case reports has been summarized. Eight of the 10 patients were women. All presented with severe ascites. Nine had polycystic kidneys. Three had moderate-to-advanced renal insufficiency, four were on hemodialysis, and one had a renal allograft. Possible predisposing factors were identified in seven patients; the most common was recent abdominal surgery, which, in three cases, was a bilateral nephrectomy. All patients had extrinsic compression of the hepatic veins and the inferior vena cava by hepatic cysts, and four had proven superimposed thrombosis of the inferior vena cava and/or hepatic veins. In the patients seen in this institution, magnetic resonance imaging was helpful in determining the level of obstruction in the inferior vena cava and the patency of the hepatic and portal veins. The outcome was worse in the patients with thrombosis; one recovered after a portocaval shunt, and the remaining three patients died. On the other hand, five of the six patients without thrombosis recovered after alcohol sclerosis of a large dominant cyst (one patient) or after hepatic resection and cyst fenestration (four patients). Hepatic venous outflow obstruction probably has been underrecognized as a cause of portal hypertension, ascites, and liver dysfunction in polycystic liver disease. The diagnosis can be reliably established with current imaging techniques, especially magnetic resonance imaging.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873729 TI - Renal cystic disease and ammoniagenesis in Han:SPRD rats. AB - Cyst formation in conditions associated with increased renal ammoniagenesis (hypokalemia, distal renal tubular acidosis, renal mass reduction) and experimental links between increased ammoniagenesis and interstitial inflammation have suggested a role for ammonia in the pathogenesis of polycystic kidney disease (PKD). To explore this hypothesis, Han:SPRD rats, a PKD model that affects male more severely than female animals, have been used. Heterozygous cystic (Cy/+) and homozygous normal (+/+) male and female offspring of Cy/+ rats were divided at 3 wk of age into control groups drinking water and experimental groups drinking 300 mM NH4Cl, 300 mM KHCO3, 200 mM KHCO3, 200 mM KCl, 200 mM NaHCO3, or 200 mM NaCl. At 2 months of age, the rats were kept fasting from 8:00 p.m. to 8:00 a.m. in metabolic cages and urine samples were collected under mineral oil. The rats were then weighed and anesthetized for the collection of blood and kidneys. The administration of 300 mM NH4Cl, and to a lesser extent that of 200 mM NaCl, was accompanied by an increase in the urinary excretion of ammonia and aggravation of the renal cystic disease. On the other hand, the administration of 300 mM KHCO3, 200 mM KHCO3, or 200 mM NaHCO3 lowered the urinary excretion of ammonia and markedly reduced the severity of the cystic disease and interstitial inflammation. The administration of 300 mM KHCO3, and to a lesser extent that of 200 mM KHCO3, resulted in the precipitation of calcium phosphate in the medullary collecting ducts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873730 TI - Renal tubular cell protein breakdown in uninephrectomized and ammonium chloride loaded rats. AB - Kidney enlargement after unilateral nephrectomy or the induction of a systemic acidosis with ammonium chloride is associated with an increase in kidney protein content. This reflects an imbalance between protein breakdown and protein synthesis. Because it has been shown in diabetic nephromegaly that depressed protein breakdown contributes to the increase in kidney protein content, this study examined whether altered protein breakdown is common to all forms of renal hypertrophy. Accordingly, protein turnover was measured in isolated proximal tubules from kidney in rats undergoing renal enlargement after uninephrectomy or chronic ammonium chloride-induced acidosis. In both conditions, kidney protein content and protein synthesis ([14C]valine incorporation) increased significantly. Fractional protein degradation was depressed in renal tubules isolated from the acidotic rats and was accompanied by a decrease in proximal tubule cathepsin B and combined B and L activities. These changes are comparable to earlier observations with the diabetic kidney. In contrast, after unilateral nephrectomy, protein breakdown is not reduced, and it can reasonably be concluded that, in this condition, protein gain reflects increased protein synthesis alone. It was concluded that the pattern of protein turnover leading to protein accretion in renal hypertrophy varies according to the initial stimulus for renal growth. PMID- 7873731 TI - Changes in the kinetics and biopotency of luteinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin. AB - To investigate the effect of recombinant human erythropoietin (rh-EPO) on the hypothalamo-pituitary-gonadal axis in end-stage renal failure, plasma luteinizing hormone (LH) concentration release was assessed by frequent blood sampling (every 10 min), both during an 8-h baseline period and after stimulation with an iv bolus of gonadotropin-releasing hormone (GnRH). Seven adult hemodialyzed men were studied before and after partial correction of anemia by rh-EPO treatment. LH was determined by an in vitro Leydig cell bioassay (bio-LH) and a highly sensitive immunoradiometric assay. Pulsatile bio-LH secretion and clearance characteristics were assessed by multiple-parameter deconvolution analysis. Although the rh-EPO treatment did not lead to a change in average concentrations of plasma bio-LH, the mass of hormone released per secretory burst more than doubled, and the estimated bio-LH production rate increased from 8.8 +/- 2.3 to 15.6 +/- 5.2 IU/L per hour (P = 0.05). The lack of change in mean plasma bio-LH is explained by a simultaneous decrease in plasma half-life from 106 +/- 27 to 67 +/- 19 min (P < 0.02). The decrease in the plasma half-life of bio-LH was closely associated with the rise in hematocrit, suggesting an effect of the increased red blood cell mass on LH distribution space and elimination kinetics. As a consequence of the changes in hormone kinetics, the incremental amplitudes of the plasma concentration pulses of bio-LH increased from 112 to 121% of nadir levels (P < 0.05), resulting in a more distinctly pulsatile pattern of hormone signals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873732 TI - Safety and efficacy of recombinant human erythropoietin in correcting the anemia of patients with chronic renal allograft dysfunction. AB - Recombinant human erythropoietin (rHuEPO) is effective in correcting anemia in hemodialysis, peritoneal dialysis, and predialysis patients. Limited studies in patients with failing renal allografts suggest a similar efficacy but provide little information concerning benefits, dose requirements, or adverse events. This study examined these considerations in a group of 40 patients (18 men; 22 women) aged 40.3 +/- 13.8 yr with stable, chronic renal allograft failure. All patients had a hemoglobin < 95 g/L and a serum creatinine > 250 mumol/L at baseline. Patients received rHuEPO (50 U/kg sc) three times weekly for 24 wk along with iron po if serum ferritin was < 100 micrograms/L. Mean hemoglobin rose from 78.9 +/- 10.4 to 102.6 +/- 18.4 g/L after 24 wk. Mean rHuEPO dose at 24 wk was 129.8 +/- 81.9 U/kg per week. With oral iron supplementation only, serum ferritin fell throughout the 24 wk, whereas serum iron, transferrin saturation, and total iron-binding capacity remained stable. Quality of life was assessed by use of the general Sickness Impact Profile and the disease-specific Transplant Disease Questionnaire measures at baseline and every 8 wk during rHuEPO therapy. Significant improvement was noted in global Sickness Impact Profile scores and in four of five dimensions of the Transplant Disease Questionnaire. Serious adverse events were infrequent. No change in mean systolic or diastolic blood pressure was noted, although there was a significantly increased need for antihypertensive drugs in 18 patients (P = 0.0002). A significant inverse correlation was noted between baseline renal function and maintenance rHuEPO dose (r = -0.45; P < 0.05). Twelve patients returned to dialysis during the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873734 TI - Causes of death in dialysis patients: racial and gender differences. AB - The risk of death in the dialysis population is high and has previously been shown to be accentuated in male (versus female) and white (versus black) subgroups. To better understand the difference in mortality among these subgroups, the causes of death between males and females as well as between whites and blacks adjusting for age, cause of ESRD (diabetic versus nondiabetic), dialysis modality, and time on dialysis (< 1 yr versus > 1 yr) were compared, with national data obtained from the U.S. Renal Data System. A total of 42,372 deaths occurring over 170,700 patient years at risk were analyzed. Males had a 22% higher risk of death than females (P < 0.001), attributable to a higher risk of death due to acute myocardial infarction (relative death rate ratio (RR) = 1.48; P = 0.001), all other cardiac causes (RR = 1.3; P = 0.001), and malignancy (RR = 1.59; P < 0.001). Whites had a 29% higher risk of death than blacks (P < 0.001), accounted for by an increased risk of death due to acute myocardial infarction (RR = 1.34), all other cardiac causes (RR = 1.30), withdrawal from dialysis (RR = 2.72) (all P < 0.001), and infection (RR = 1.09; P = 0.005). This analysis expands the knowledge and understanding of the excess mortality seen in male and white subgroups, which is a necessary step in designing strategies to reduce the high mortality in dialysis patients. PMID- 7873733 TI - Resolution of posttransplant hypertension after liver transplantation despite impaired glomerular filtration. AB - Hypertension developing after transplantation is characterized by widespread vasoconstriction including the kidney. Late resolution (mean, 29 +/- 4 months) of posttransplant hypertension has been observed in 15 (Group I) of 278 subjects monitored after liver transplantation. These studies were undertaken to define the systemic and renal changes associated with resolution, as compared with a group matched for age, sex, and time after transplant who remained hypertensive (Group II; N = 15) or a group who never developed hypertension (Group III; N = 23). Blood pressure during resolution paralleled changes in the systemic resistance index, which fell from 3,052 +/- 548 to 1,872 +/- 205 dyne/s.cm5/m2 (P < 0.01). GFR and RBF remained low, despite the resolution of hypertension, and renal vascular resistance did not change. Circulating endothelin levels remained above normal in all transplant recipients (Group I, 11.9 +/- 3.0 versus normal subjects, 7.0 +/- 1.1 pg/mL; P < 0.05), and urinary prostacyclin excretion was suppressed (880 +/- 120 versus 2,247 +/- 187 ng/day; P < 0.01). No hormonal differences were apparent between transplant groups. These results demonstrate the capacity for systemic vasodilation to occur after transplantation, independent of vascular tone in the kidney. They further suggest that renal vasoconstriction and impaired GFR alone are not sufficient to explain de novo hypertension after transplantation. PMID- 7873735 TI - Mismatch in elastic properties around anastomoses of interposition grafts for hemodialysis access. AB - Arteriovenous (AV) fistulas for hemodialysis access, constructed with the use of interposition grafts, are often complicated by intimal hyperplastic stenosis, mainly occurring at the venous anastomosis. In this study, mismatch in elastic properties around the arterial and venous anastomoses of graft AV fistulas in humans was quantified in order to find clues for the predisposition of intimal hyperplasia to develop at the venous anastomosis. The elastic properties of graft AV fistulas in 31 hemodialysis patients were investigated by the use of vessel wall Doppler tracking, 2 wk after construction. Nine saphenous vein grafts, 8 expanded polytetrafluoroethylene (ePTFE) grafts, and 14 stretch-PTFE (sPTFE) grafts were measured at the arterial inflow segment, the proximal graft segment, the distal graft segment, and the venous outflow segment. Area increase (AI), representing the capacity of the vessel wall to store blood volume, and relative distension, representing the intrinsic elastic properties, were calculated from diameter and distension. A decrease in AI was observed in the arterial anastomoses of all graft types. An increase in AI was found in the venous anastomosis of ePTFE and sPTFE grafts. Higher values for AI and relative distension were found at the proximal and distal graft segments of the saphenous vein grafts when compared with the prosthetic grafts. In the sPTFE grafts, the level of AI was maintained along the graft, whereas in the ePTFE grafts, a decrease in AI was found. In the arterial anastomoses of AV fistulas, a decline in the capacity to store blood volume was observed. By contrast, an increase in the capacity to store blood volume was found in the venous anastomoses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873736 TI - Vitamin D receptor gene expression in mammalian kidney. AB - The vitamin D-receptor protein and its mRNA were localized in microscope sections of paraffin-embedded mammalian kidneys by means of immunocytochemistry and in situ hybridization, respectively. A monoclonal antibody against chicken intestinal vitamin D receptor immunostained the nucleus and cytoplasm of cells within the distal convoluted tubule, connecting segment, and initial cortical collecting duct of both rats and pigs. Although fainter, immunostaining also was present over proximal tubular cells. (35S)UTP-labeled cRNA probes were detected over both the proximal and distal portions of the mouse nephron, but silver grain densities were 5.8-fold greater over the latter. In conclusion, localization of both the vitamin D-receptor protein and its mRNA in both the proximal and distal nephron of adult mammals suggests that the gene for this protein is expressed in cells at both of these sites. The intensity of immunostaining and the density of cRNA-associated silver grains suggest that vitamin D-receptor gene expression is greatest in the distal nephron. PMID- 7873737 TI - Phosphate depletion impairs leucine-induced insulin secretion. AB - Phosphate depletion (PD) in vivo causes a sundry of abnormalities in pancreatic islets including a rise in cytosolic calcium, low ATP content, reduced Ca2+ ATPase and Na(+)-K+ ATPase activity, and impaired insulin secretion in response to glucose or potassium. L-Leucine is a strong secretagogue that triggers insulin secretion by deamination to alpha-ketoisocaproic acid (KIC) and the subsequent metabolism of the latter to ATP and by the activation of glutamate dehydrogenase (GLDH), which acts on glutamate to generate alpha-ketoglutarate, the metabolism of which results in ATP production. The generation of ATP triggers events that lead to insulin secretion. It is not known whether PD impairs leucine-induced insulin secretion, and the cellular derangements that are involved in such an abnormality are not defined. These issues were studied in PD rats and in pair weighed normal animals as controls. D-Leucine uptake by islets from PD rats is normal, but both leucine- and KIC-induced insulin secretions are impaired and the activity of branched-chain keto acid dehydrogenase, which facilitates the metabolism of KIC, is reduced. Both leucine and 2-aminobicyclo (2-2-1) haptene failed to stimulate GLDH and to augment the generation of alpha-ketoglutarate in the islets of PD rats. Also, the concentration of basal alpha-ketoglutarate was significantly higher in the islets of PD rats, suggesting that its metabolism is impaired. In addition, the activity of glutaminase is significantly reduced, an abnormality that would result in decreased production of glutamate, the substrate for GLDH. The data show that PD impairs leucine-induced insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873738 TI - Drooping upper eyelids and polycystic kidney disease. AB - Over the last 26 yr, 33 cases and/or families of patients with autosomal dominant polycystic kidney disease (ADPKD) and a particular appearance of the eyes have been observed. ADPKD was unremarkable and in most cases had led to the usual slow development of end-stage renal failure. The facial feature concerned the upper eyelid, which drooped obliquely over the eyeball with a fold hiding the upper segment of the iris (blepharochalasis). The aspect was so typical that the diagnosis of ADPKD was suggested on first contact with new renal patients. All affected patients were white, of various origins, including French, Polish, Scandinavian, Italian, and Spanish. In retrospect, drooping eyelids had been present in the parents and/or grandparents who had died of renal failure, with or without an established diagnosis of ADPKD. In order to disclose the cosegregation of blepharochalasis with ADPKD, the screening of its prevalence in a well circumscribed region with a catchment population of 410,000 was undertaken. The facial feature was found in 24 (32%) of 75 ADPKD families. Family transmission was confirmed in those kindreds, because at least two members suffered from ADPKD. Cosegregation was sought by analyzing family group photographs taken over several generations, the oldest member of which was born in 1973. All members with blepharochalasis had died of renal failure or are presently being followed up for ADPKD. A bibliographic search showed that the association of ocular and/or eyelid deformities and various inborn renal diseases is far from rare, suggesting a simultaneous event in the embryonic timetable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873739 TI - Festschrift for Jacob Lemann, Jr. PMID- 7873740 TI - Acid-base status and intracellular pH regulation in lymphocytes from rats with genetic hypertension. AB - This article reviews work from this laboratory dealing with acid-base status and intracellular pH (pHi) regulation in rat genetic models of hypertension. With freshly isolated thymic lymphocytes, pHi and its regulation were examined in the spontaneously hypertensive rat (SHR). In this rat model, pHi was found to be reduced as compared with that of lymphocytes from normotensive Wistar-Kyoto (WKY) rats. The activity of the Na+/H+ antiporter assessed after stimulation by acute cell acidification was similar in lymphocytes from SHR and WKY rats both in the nominal absence of HCO3- and in media containing HCO3- (22 mM). The kinetic properties of the Na+/H+ antiporter, examined as a function of pHi with the Hill kinetic model, revealed no significant differences between lymphocytes from SHR and WKY rats. The kinetic properties of the Na(+)-dependent and Na(+)-independent Cl(-)-HCO3- exchangers, examined as a function of external Cl-, were also virtually identical in lymphocytes from SHR and WKY rats. Unlike the Na(+)-H+ exchanger and the Na(+)-independent Cl(-)-HCO3- exchanger, which had their highest activities at extremes of pHi (low pHi, Na(+)-H+ exchanger; high pHi, Na(+)-independent Cl(-)-HCO3- exchanger), the Na(+)-dependent Cl(-)-HCO3- exchanger had its maximal activity near steady-state pHi. In Dahl/Rapp salt sensitive rats with hypertension, the pHi of thymic lymphocytes was also reduced as compared with that of normotensive salt-resistant animals. In this model, renal net acid excretion in salt-sensitive rats was augmented as compared with that of salt-resistant rats. The increase in renal acid excretion was due to an increase in both ammonium and titratable acid excretion and was observed while animals were placed on high, normal and low salt diets. The findings of intracellular acidosis and enhanced renal acid excretion suggest that cellular acid overproduction is augmented in salt-sensitive hypertension. PMID- 7873741 TI - Potassium excretion: a story that is easy to digest. AB - The aim of this article is to consider how a large quantity of potassium (K+) can be excreted without the development of hyperkalemia. The hypothesis will focus on interactions between K+ and HCO3- primarily within the kidneys. It is speculated that the absorption of K+ from the gastrointestinal tract is accompanied by an initial addition of HCO3- to the body; this in turn could, via intrarenal events, promote the delivery of HCO3- to the cortical collecting duct (CCD), where interactions may permit the development of a very high rate of excretion of K+. To test one portion of this hypothesis, studies were performed in sheep because they normally consume approximately 10-fold more K+ per kilogram body weight than do humans. In the absence of a significant degree of anabolism, there is only a limited potential to shift K+ acutely into cells. Hence, an extremely large capacity to excrete K+ is required to avoid a severe degree of hyperkalemia. The excretion of K+ depends primarily on the ability to have a sustained rise in the (K) in each liter of luminal fluid exiting the CCD to very high levels and to have a large number of liters of fluid exit the terminal CCD while antidiuretic hormone is acting. A reasonable approximation of this CCD flow rate can be obtained by examining the osmole excretion rate when ADH acts. Because these sheep excreted 1,650 mosmol (2 L x 827 mosm/kg H2O) per day, a minimum estimate for volume delivery out of the CCD is 5 to 6 L/day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873742 TI - Gene expression of epithelial glucose transporters: the role of diabetes mellitus. AB - The functions of absorption of dietary glucose by the small intestine and reabsorption of filtered glucose by the renal proximal tubule are strikingly similar in their organization and in the way they adapt to uncontrolled diabetes mellitus. In both cases, transepithelial glucose and Na+ fluxes are augmented. The epithelial adaptations to hyperglycemia of uncontrolled diabetes are accomplished by increasing the glucose transport surface area and the number of the efflux glucose transporter GLUT2 located in the basolateral membrane. The signals that modify the size of the epithelium and the overexpression of basolateral GLUT2 are not known. It was speculated that high glucose levels and enhanced Na+ flux may be important factors in the signaling event that culminates in a renal and intestinal epithelium that is modified to transport higher rates of glucose against a higher extracellular level of glucose. PMID- 7873743 TI - Crystal-membrane interaction in kidney stone disease. AB - Urolithiasis is a multifaceted process that initiates with the formation of microcrystals in the urine and terminates with the formation of mature renal calculi. The attachment of crystals by the urothelium is a major event in the successful formation of the mature stone. The papillary tip is the primary site for crystal attachment and stone maturation, and the attachment process appears to be mediated by specific molecular interactions between molecular structures on the surfaces of stone crystals and molecular arrays on the surfaces of cell membranes. Animal models have demonstrated the interaction between cells and crystals, and they have suggested a correlation between cellular damage and crystal interaction, especially when crystals bind to and then break free from the tubular epithelium. Cell culture studies on inner medullary late collecting duct (IMCD) cells have demonstrated that calcium oxalate monohydrate, hydroxyapatite, and uric acid crystals bind to IMCD cells in primary culture. The attachment of these crystals to IMCD cells was crystal structure dependent, saturable, and competitively inhibitable if more than one crystal type was present at the same time. The crystals preferentially attach to cells that have lost partial or complete intercellular junctional integrity. These crystal attaching cells appear to have altered membrane composition and/or structure. Recent studies on red blood cells and IMCD cells that have been enriched with cholesterol and selected phospholipids suggest that crystal-membrane phospholipid interactions play a major role in crystal attachment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873744 TI - Urinary calcium oxalate crystal growth inhibitors. AB - Calcium stones occur because renal tubular fluid and urine are supersaturated with respect to calcium oxalate and phosphate. The process of stone formation includes crystal nucleation, growth, aggregation, and attachment to renal epithelia. Urine contains macromolecules that modify these processes and may protect against stone formation. Attention has focused especially on inhibitors of crystal growth, and several have been isolated from urine, including nephrocalcin, an acidic phosphorylated glycoprotein that contains several residues of gamma-carboxyglutamic acid per molecule; osteopontin (uropontin), a phosphorylated glycoprotein also found in bone matrix; uronic acid-rich protein, which contains a covalently bound glycosaminoglycan residue; and several others. Abnormalities in structure and/or function have been detected in some of these proteins in stone formers' urine. However, the overall ability of urinary macromolecules to inhibit calcium oxalate crystal growth is often normal in stone formers. Recently, attention has been focused on the ability of these molecules to inhibit other stages in stone formation. Nephrocalcin can inhibit crystal nucleation, for example, and both nephrocalcin and Tamm-Horsfall protein inhibit crystal aggregation. Nephrocalcin and Tamm-Horsfall protein from stone formers are less active in preventing aggregation, and under some conditions, Tamm Horsfall protein may promote the formation of crystal aggregates, especially in the presence of high concentrations of calcium. The structural abnormalities responsible for impaired inhibitory activity are not completely understood. PMID- 7873745 TI - Jacob Lemann, Jr., MD--the Milwaukee years. PMID- 7873746 TI - Hypercalciuria: lessons from studies of genetic hypercalciuric rats. AB - Human idiopathic hypercalciuria (IH) is a common cause of hypercalciuria that contributes to calcium oxalate nephrolithiasis. The disorder is characterized by normocalcemia, increased intestinal Ca absorption, and normal or elevated circulating 1,25(OH)2D3. Intestinal Ca hyperabsorption, which is a source of excess urine Ca excretion, may result from either a primary increase in renal 1,25(OH)2D3 production; a primary, vitamin D-independent defect in enterocyte regulation of Ca transport; or a secondary increase in 1,25(OH)2D3 production in response to a defect in renal tubular Ca reabsorption. Breeding male and female Sprague Dawley rats with spontaneous hypercalciuria has resulted in offspring with hypercalciuria, increased intestinal Ca absorption, and normal serum 1,25(OH)2D3. In male IH rats, vitamin D receptor (VDR) content measured by saturation binding and western blotting revealed a twofold increase in VDR number in the duodenum, kidney cortex, and splenic monocytes. The molecular basis for the increase in VDR appears not to be due to increased VDR gene expression, but may result from increased efficiency of translation of the VDR message or prolongation of the half-life of VDR. Comparable migration of normal and IH intestinal VDR on western blots and of intestinal VDR mRNA on northern blots suggests that the abundant VDR in IH rat intestine is not a mutation of the wild type VDR. These observations strongly suggest that, in IH rats, normal serum 1,25(OH)2D3 and increased VDR results in increased VDR-1,25(OH)2D3 complexes and enhanced biologic actions of 1,25(OH)2D3, including increased intestinal Ca transport. IH in rats may be the first genetic disorder due to a pathologic increase in the VDR. PMID- 7873747 TI - Idiopathic hypercalciuria: the contribution of Dr. Jacob Lemann, Jr. AB - The original contributions of Jacob Lemann to mineral metabolism, especially calcium metabolism and idopathic hypercalciuria, are reviewed. One group of studies concern acid base balance and calcium loss, showing that acid loads increase calcium loss in the urine. Another group of studies concern the calciuria of glucose or carbohydrate ingestion, with the observation that stone patients, who as a population are enriched with hypercalciuria, respond with more exaggerated calciuria to glucose loads than do normal people. Yet another body of work shows that normal men, when given noncalcemic loads of calcitriol, exhibit two essential features of idiopathic hypercalciuria--hyperabsorptive hypercalciuria and bone mineral loss on a low-calcium diet. The final group of studies presented worked on the problem of thiazide hypocalciuric action, and where the calcium goes that does not appear in the urine, as well as the effects of potassium bicarbonate and sodium loads on mineral balance and acid base status. PMID- 7873748 TI - Proton ATPases and urinary acidification. AB - Acidification of the urine is mediated by vectorial H+ transport from cells at a number of sites in the kidney. A proton ATPase has been described that appears to mediate a significant proportion of this H+ transport. In particular, in proximal tubule and collecting duct, there is evidence both for the presence of transporter protein and for H+ transport with features that have been identified with it. This review highlights some of the unresolved questions regarding this transporter, specifically, its distribution and relationship to the vacuolar pump present in endocytotic vesicles, how physiologic control is asserted, and its role in pathophysiology. The review discusses in greater detail the issue of whether the vacuolar H+ ATPase is responsible for all of the urinary acidification and concludes that it probably is not. Specifically, compelling evidence for acidification at sites in the kidney that appear to lack this transporter is presented. In addition, the evidence for the presence in the kidney of a gastric-type H(+)-K+ ATPase is also reviewed. The evidence appears to be strong for a K(+)-stimulated ATPase that is sensitive to omeprazole and SCH 28080, the prototypical H(+)-K+ ATPase inhibitors; however, uncertainties remain because of problems of transport inhibition specificity and discordant results of molecular biologic studies. PMID- 7873749 TI - Generalized resistance to thyroid hormone: identification of a novel c-erbA beta thyroid hormone receptor variant (Leu450) in a Japanese family and analysis of its secondary structure by the Chou and Fasman method. AB - Generalized resistance to thyroid hormone (GRTH) is characterized by elevated circulating levels of thyroid hormone in the presence of a eumetabolic state and failure to respond to triiodothyronine. Various point mutations in the c-erbA beta thyroid hormone receptor gene are known to be responsible for different phenotypes of GRTH. We herein report a new c-erbA beta variant in a Japanese family. The variant consisting of a cytosine to adenine base substitution at nucleotide position 1650 altered phenylalanine to leucine in codon 450 in the T3 binding domain of c-erbA beta. This base substitution was found in one allele of the 2 affected members of the family. The in vitro translation products of this mutant c-erbA beta gene demonstrated a significantly reduced T3-binding affinity. The secondary structure of this mutant thyroid hormone receptor predicted by the Chou and Fasman method included a new turn in the alpha helix structure in the T3 binding domain. We also discuss the secondary structures of the previously reported mutant receptors. PMID- 7873750 TI - DNA fingerprinting involving fluorescence-labeled termini of any enzymatically generated fragments of DNA. AB - We have developed a new fluorescence-based method for DNA fingerprinting that does not require a fluorescent linker or a synthetic oligonucleotide primer, both of which are normally used for labeling of DNA. Cosmid DNAs are digested with appropriate restriction enzymes and the 3' termini of DNA fragments are labeled with the corresponding, fluorescent dye-conjugated dideoxynucleotide triphosphate terminator (dye-ddNTP) by the Klenow fragment of DNA polymerase I from Escherichia coli, which has 3'-->5' exonuclease and replacement activities as well as its main 5'-->3' polymerase activity. Samples are separated on a DNA sequencing gel and data are analyzed by application of both the Version 0.3.8a mapper program (Applied Biosystem Inc., Foster City, CA) and our Overlap I program that facilitate rapid analysis of the frequency of overlapping of cosmid DNAs. Using this method we have determined the overlap frequency of DNA fragments of each cosmid clone from the mouse MHC class I gene cluster. PMID- 7873751 TI - Genomic structure and chromosomal localization of processed pseudogenes for human RBP-Jk. AB - The functional gene for human recombination signal sequence-binding protein (RBP Jk) and corresponding processed psudogenes have been isolated from various species, such as Drosophila, Xenopus, mouse, and human. Here we report the isolation of another two genomic pseudogenes of human RBP-Jk, named K2 and K7, from a cosmid library of Hela cells. The nucleotide sequences of both genes exhibited more than 95% homology to the functional human gene for RBP-Jk. Moreover, they did not contain any intron sequences and were interrupted by several stop codons in all frames. In situ hybridization demonstrated that the pseudogenes, K2 and K7, were localized at chromosomes 9p13 and 9q13, respectively. Their physical maps differed from those of the true functional gene and of the pseudogenes reported previously by Amakawa et al. (1993). PMID- 7873752 TI - Carrier detection of Werner's syndrome using a microsatellite that exhibits linkage disequilibrium with the Werner's syndrome locus. AB - Werner's syndrome (WS) is a rare autosomal recessive disorder, one of the progeroid syndromes, characterized by features of premature aging. The genetic defect in WS is unknown but recently the genetic linkage of WS to several markers on the short arm of chromosome 8 has been reported. Genetic analysis of 25 families with WS demonstrated that D8S339 was the closest marker linked to the gene locus for Werner's syndrome (WRN), with a peak lod score of 18.29 at recombination frequency 0.001, and showed a linkage disequilibrium with the WRN locus. We studied two unrelated families with WS using ANK1, D8S339, and D8S360. The mutative haplotype identified through the generations in pedigrees provides a means of carrier detection and presymptomatic diagnosis. PMID- 7873753 TI - Isolation of human chromosome 21-specific cosmids and their uses in mapping of cosmid contigs on chromosomal subregions. AB - A cosmid library of 3 x 10(5) clones has been constructed from a human x hamster hybrid cell line, 153E9a3, which contains human chromosome 21 (HC21) as the only human chromosome. From 56,500 clones of this library, 229 HC21-specific cosmids have been isolated by their hybridization to total human DNA and by their failure to hybridize to total Chinese hamster DNA. The cosmids isolated were then characterized, of these, 28 cosmids (12.2% of those tested) contained Not1 site(s), and 41 cosmids were localized on the eight subregions of HC21 by differential hybridization with Alu-PCR products obtained from a hybrid mapping panel. The cosmids localized were further integrated into the existing contigs using the end-specific probes of the clone insert. Therefore, they provided useful anchor points for contig mapping and walking. PMID- 7873754 TI - Direct mapping of the human TATA box-binding protein (TBP) gene to 6q27 by fluorescence in situ hybridization. AB - TBP (TATA box-binding protein) participates in the expression of eukaryotic genes transcribed by RNA polymerases I, II, and III. Molecular cloning of human TBP revealed that the N-terminal region contains a polymorphic (CAG)n repeat. We report here the direct localization of human TBP gene to chromosome 6q2705-->qter region by fluorescence in situ hybridization, using the cDNA clone with or without the (CAG)n repeat as a probe. PMID- 7873755 TI - The attitude of Japanese physicians regarding genetic service for autosomal dominant polycystic kidney disease (ADPKD). AB - A questionnaire carried out among Japanese physicians revealed that a strong demand for genetic counseling among patients and families with autosomal dominant polycystic kidney disease (ADPKD). In contrast, the awareness of physicians regarding genetic counseling for the disease seemed to be low. For example, 66.0% of the respondents to the questionnaire revealed a negative attitude to providing genetic counseling for patients, and 30.7% of the respondents did not know that most types of polycystic kidney disease are inherited disorders. With the advance of scientific research, the demand for genetic counseling among patients is bound to increase. Therefore, the providers of genetic counseling including the physicians are now pressed to improve their services. PMID- 7873756 TI - Chromosome 1q terminal deletion resulting from de novo translocation with an acrocentric chromosome. AB - Distal deletion of chromosome 1q has been reported in nearly 30 patients, all being associated with a deletion ranging from the 1q42 or q43 band to 1qter region. Here, we describe a girl with 1q terminal deletion resulting from an unbalanced de novo translocation t(1;D or G)(q44;p11), as revealed by the presence of a satellited feature and an NOR-stained region at the tip of 1q. We suggest that most of the phenotypic abnormalities seen in patients with 1q distal deletion are attributable to the monosomy for band 1q44. PMID- 7873757 TI - Identification of a single base polymorphism in intron 2 of the c-fos gene and its detection by mismatched PCR-RFLP. AB - A T-->C transition in intron 2 of the c-fos gene was identified by sequencing analysis (Fig. 1). A simple method to detect this polymorphism was developed by mismatched PCR-RFLP. Allele frequency of this polymorphism was determined in the Japanese and in the Caucasian, separately. PMID- 7873758 TI - Dinucleotide repeat polymorphism at the D8S1055. PMID- 7873759 TI - Dinucleotide repeat polymorphism at the D8S1053. PMID- 7873760 TI - Six dinucleotide repeat polymorphisms on chromosome 7. PMID- 7873761 TI - An apparent balanced translocation between chromosomes 7 and 13 [t(7;13)(p15;q32)] in a 47,XYY individual. PMID- 7873762 TI - Significance of the 'biologic width' with respect to root-form implants. PMID- 7873763 TI - Prosthetically-guided implant placement: the provisional restoration and the surgical template. PMID- 7873764 TI - [A comparison of preventive health behaviors among middle-aged males in different types of communities in Tokyo]. AB - Preventive health behaviors of middle-aged men living in areas of Tokyo with differing mortality rates were analyzed to determine if regional differences exist and if so why. Information on seven different health behaviors (cigarette smoking, physical activity, alcohol consumption, food intake pattern, taking breakfast, hours of sleep, and relative weight) were obtained by a survey among the sample randomly selected from men 35 to 64 years of age living in two separate communities, Koto-Ward with a high middle-aged male mortality and Bunkyo Ward where it is low. The following results were obtained; 1) In Koto-Ward where middle-aged male mortality is high, the proportion of interviewees who participated physical activity more than once a week and had good food intake patterns was significantly lower than in Bunkyo-Ward. 2) Regional differences in both physical activity and food intake pattern appear to be due to differences in proportion of higher educational attainment which is associated with more frequent participation in physical activity and better food intake patterns. PMID- 7873765 TI - [Relationship between occupational factors and medical indicators related to arteriosclerotic diseases]. AB - The relationship between occupational factors and indicators related to arteriosclerotic diseases which include blood pressure, total cholesterol, triglyceride, HDL-cholesterol, body mass index, and HMS (Hitachi mental health scale) score. The study subjects were 7226 male electric company employees (40 to 59 years old). Records of annual health examinations were reviewed, and those of 3553 blue-color workers and 1860 white-color workers were used for analyses. The main results were as follows: Work style (overtime work and frequency of business trips) was strongly related to life style. Overtime work and walking time from home to the workplace did not relate to indicators of arteriosclerotic diseases. However, frequency of business trips, working posture and job category were related to most of the indicators. Smoking and frequency of drinking were strongly related to the indicators in both blue-color and white-color workers. In both blue-color and white-color workers, HMS score was not related to work style, but related strongly to psychological factors. In white-color workers, HMS were also related to life style. In addition, this study suggests that a cohort study about the progress of arteriosclerotic diseases in middle-aged workers is necessary, and that more accurate information on work style should be obtained for further investigation. PMID- 7873766 TI - [Results of annual health examination for the aged provided by the law that are predictive of increased mortality risk]. AB - Possible risk factors associated with mortality were studied in a community using data derived from annual mass health examinations for the aged mandated by law. A total of 1,804 adults (685 men and 1,119 women) aged 40 or older in A-town, located on Tsushima Island, Nagasaki Prefecture, Japan who had participated in annual health examinations at least once between 1984 and 1990, were followed for a mean period of 4.9 years. After adjustment for age using Cox proportional hazards models, in men liver dysfunction (aspartate aminotransferase > 40 U/l or alanine aminotransferase > 35 U/l), fasting blood glucose > or = 110 mg/dl and glucosuria, and in women serum creatinine > or = 1.2 mg/dl, fasting blood glucose > or = 110 mg/dl and proteinuria were found to be associated with a significantly increased risk of total mortality. In multivariate analysis using all independent variables that were significantly associated with mortality in age-adjusted bivariate analysis, in men liver dysfunction and hyperglycemia, and in women hypercreatininemia and hyperglycemia, were significant predictors of mortality. These independent variables remained significant or marginally significant predictors of total mortality even after excluding the effects of 3 pancreatic cancer cases with liver dysfunction or hyperglycemia or 12 deaths within the first year of follow-up, being associated with at least two-fold increased hazard rate ratios. From these results, it is recommended that persons with these risk factors be followed intensively and counseled by public health personnel to modify risk factors. PMID- 7873767 TI - [Contamination of hot water supply in office buildings by Legionella pneumophila and some countermeasures]. AB - An assessment of the contamination by Legionella species of hot water supplied to office buildings was made based on 80 samples of water from 3 types of systems as follows: 20 samples supplied from instantaneous heaters, 20 samples from hot water storage type systems, and 40 samples from circulation type systems. Legionella spp. were detected in two samples (10.0%) from hot water storage systems and five samples (12.5%) of the circulation type. The number of Legionella spp. was 2.0 x 10-8.4 x 10(2) CFU/500 ml. All isolated strains were identified as Legionella pneumophila. All hot water samples with Legionella spp. showed a temperature range from 41-55 degrees C. Contamination may easily occur in hot water storage and circulation type systems, due to their presence for prolonged periods. Hot water may be therefor be a source of Legionnaires' disease. It is clear from the present study that Legionella spp. survived over long periods and proliferated considerably. Elimination of this organism requires careful cleaning of hot water storage tanks but this alone may not be sufficient. Heat treatment for 20 hours at 70 degrees C was found to be adequate for complete elimination. Experimentally, complete sterilization from Legionella spp. within 5 minutes was demonstrated by heating at 60 degrees C. As a countermeasure temperature of hot water should be maintained at more than 55 degrees C, as the best means for elimination while also giving consideration to the prevention of scalding. PMID- 7873768 TI - [Chlordane accumulations in adipose tissue of mice chronically exposed to chlordanes in indoor air]. AB - Chlordane concentrations were analyzed in the adipose tissue of mice after prolonged inhalation of low levels of chlordanes in indoor air. After inhalation of 4.22-11.36 micrograms/m3 chlordanes (total of 5 compounds) in air for 1-6 months, high levels of chlordanes (4.19-11.63 ppm, total of 5 compounds and 2 metabolites) were found in the adipose tissue. Transnanochlor, which accounted for only 14% of the total chlordane in the inhaled air, showed a high percentage (50%) in the adipose tissue, followed by 2 metabolites, i.e., oxychlordane (25%) and heptachlorepoxide (22%). Little transchlordane, cis-chlordane, or heptachlor, which accounted for high percentages of the total chlordane inhaled, was detected in the adipose tissue. A low level of cis-nonachlor was observed in the adipose tissue, and its percentage was similar to that in the air (2%). The level of chlordane exposure and the adipose tissue chlordane concentration was closely correlated (r = 0.9077, p < 0.01), showed a dose-effect relationship. These findings suggest that chlordanes such as trans-nonachlor, oxychlordane, and heptachlorepoxide may accumulate in the adipose tissue of people living in an environment containing even low levels of chlordanes and that there is a risk from indoor air contamination by chlordanes. PMID- 7873769 TI - [Evaluation of the effective use of the "health notebook"]. AB - Since 1983, with the institution of the "Health Service Law for the Aged", the "health notebook" has been issued to people aged 40 years and over in order to aid in management of their health. Few people actually fill their health data in notebook by themselves. In order to develop effective use of the health notebook by residents and health professionals, the uses of the health notebooks by residents aged 40 years and over, public health nurses, and physicians were investigated. Three hundred and fifty four residents aged 40 and over, 41 public health nurses, and 18 physicians were studied in 1990, in Yamagata city. A majority of residents took their health notebooks with them to health consultations, and public health nurses used the notebooks to provide advice to them. Public health nurses effectively issued the health notebooks to residents using occasions where residents gathered. Some physicians reported that health notebooks were useful for motivating the people to maintain their health, while others preferred using a health card media. When comparing the health notebooks to the maternity passbooks, health notebooks need to be more easily utilized by users for recording information, and their value should be effectively explained to them. Furthermore, in order to promote self-care behaviors, greater use of health notebooks by all health professionals in indicated. PMID- 7873770 TI - [Associations of reported and recorded height, weight and blood pressure]. PMID- 7873771 TI - Diurnal, photoperiodic, and age-related changes in plasma growth hormone levels in the golden hamster. AB - The golden hamster has been used extensively as an animal model for the study of both circadian and seasonal rhythms, and their regulation by the light-dark (LD) cycle. More recently, this species has been used to examine how the generation and entrainment of circadian rhythms are altered in advanced age. Recent studies in both humans and rodents indicate that age-related changes in the diurnal rhythm of pituitary growth hormone (GH) release may mediate some of the adverse effects of aging on a variety of physiological systems. As a first step in determining whether or not age-related changes in circulating GH levels are associated with changes in the regulation and/or expression of circadian rhythms, the effects of age on both the ultradian and diurnal patterns of plasma GH levels were determined in 3- to 22-month-old male hamsters that were bled every 15 min for a 24-hr period while entrained to an LD 14:10 light cycle. An additional study involving a similar blood collection protocol examined whether or not the length of the day is involved in the regulation of plasma GH levels. Although the frequency of pulsatile GH release did not change with advanced age, both the mean levels of GH per sample and the mean amplitude per pulse of GH were significantly elevated in 3- to 4-month-old animals, compared to animals that were 12-13, 15 16, or 21-22 months of age. In hamsters aged 3-4 and 12-13 months, there was an increase in both mean levels and the mean amplitude per pulse of GH, but not pulse frequency, during the night as compared to daytime values. No such diurnal rhythm was detected in the two groups of older animals. A clear diurnal rhythm in GH levels was also detected in animals maintained in a short-day (LD 6:18) cycle, and the mean levels of GH per sample were greater in hamsters maintained on short compared to long (LD 14:10) days. These results indicate that there are pronounced age-related changes in pituitary GH release in the hamster, and that both the time of day and the length of the day influence the pattern of GH release. PMID- 7873772 TI - The effect of short-photoperiod exposure on tuberoinfundibular dopamine neurons in male and female Syrian hamsters. AB - In male hamsters, exposure to a short photoperiod results in a significant decrease in median eminence (ME) dopamine (DA) concentrations. The mechanism responsible for this decrease in DA is unknown. The experiments described in this paper were designed to examine the effects of photoperiod on DA metabolism and synthesis in the ME to determine if a change in these processes is responsible for the short-photoperiod-induced decrease in ME DA concentrations. In the first experiment, the metabolism of DA in tuberoinfundibular dopamine (TIDA) neuronal terminals was determined by measuring ME concentrations of 3,4 dihydroxyphenylacetic acid (DOPAC; a major metabolite of DA) and DA in male and female hamsters housed in long and short photoperiods. In both males and females, exposure to the short photoperiod induced a collapse of the reproductive system and a reduction in circulating prolactin. In males, but not in females, exposure to the short photoperiod reduced ME DA concentrations; however, DOPAC concentrations were not affected by photoperiod. Thus, the decrease in ME DA seen in males is not the result of an increase in DA metabolism. In the second experiment, tyrosine hydroxylase (TH) activity in the ME of males was determined by injecting animals housed in long and short photoperiods with a L-aromatic amino acid decarboxylase inhibitor (NSD 1015) and measuring 3,4 dihydroxyphenylalanine (DOPA). Consistent with Experiment 1, ME DA concentrations were significantly decreased in gonadally regressed males housed in a short photoperiod; however, ME DOPA accumulation was not affected. Thus, the observed decrease in DA is not the result of a decrease in TH activity in the ME. The results of the experiments presented here indicate that (1) in males but not females, the decrease in circulating prolactin seen in animals housed in a short photoperiod for 12 weeks is associated with a decrease in ME DA concentrations, and (2) the decrease in ME DA seen in males housed in a short photoperiod is not the result of an increase in DA metabolism or a decrease in synthesis by TIDA neurons. PMID- 7873773 TI - Thyroidectomy does not affect the daily or free-running rhythms of plasma melatonin in European starlings. AB - Thyroidectomy results in the suppression of reproductive photoperiodic responses in starlings. Could this be a consequence of an effect on perception of daylength or on circadian pacemakers? Daily changes in plasma melatonin concentrations were monitored in intact and thyroidectomized starlings held in long days (LD 16:8) and short days (LD 8:16), and in intact and thyroidectomized starlings allowed to free-run in constant darkness from long days or short days. In long days and short days, melatonin was low during the light period and high during darkness. There was no difference between intact and thyroidectomized birds. In free running birds, the melatonin profile of the preceding long day or short day was retained during the first day of constant darkness, with peak levels occurring at the same time they did during the light-dark cycles. Again there was no difference between intact and thyroidectomized birds. These data demonstrate that either the photoreceptive and circadian mechanisms driving melatonin secretion are independent of those concerned with reproductive photoperiodic responses, or that thyroidectomy affects reproduction "downstream" from the photoreceptive circadian apparatus. PMID- 7873774 TI - Naps as integral parts of the wake time within the human sleep-wake cycle. AB - Thirteen subjects lived singly in an isolation unit without temporal cues for an average time span of 32 days. They signaled the times when they woke up, took a meal, and retired, noting in their diaries what kind of sleep (nap or main sleep) they were going to have. In five subjects the free-running circadian rhythms remained internally synchronized. The other eight subjects became internally desynchronized, with different periods in the sleep-wake cycle and in the rhythm of body temperature, or developed a "circa-bi-dian" rhythmicity (i.e., a state of the circadian system in which the temperature rhythm regains synchrony with the sleep-wake cycle in a 2:1 ratio). The duration of naps was positively correlated with the duration of wake time (after subtraction of the nap), as well as with the duration of wakefulness preceding the nap. In contrast, the duration of main sleep was negatively correlated with the preceding wake time. It is concluded that naps are integral parts of the wake time, and that they follow the rules known from intermeal intervals and the perception of long time intervals such as 1 hr. PMID- 7873775 TI - Chronobiological theories of nonseasonal affective disorders and their implications for treatment. PMID- 7873776 TI - Light-induced phase shifts in tau mutant hamsters. AB - Phase shifts produced by single 1-hr light pulses were compared in homozygous tau mutant and wild-type hamsters after several different kinds of pretreatment regimens. There was a dramatic increase in the magnitude of phase delays in the mutant hamsters as they were kept for progressively longer times in constant darkness (DD), and a smaller increase in the magnitude of phase advances. Under the same conditions a small increase in the magnitude of phase delays and no significant increase in phase advances occurred in the wild-type hamsters. After only 7 days in DD the phase response curves (PRCs) of mutant and wild-type hamsters were both type 1 and were indistinguishable from each other, whereas after 49 days in DD the PRCs of mutant hamsters had become type O. Mutant hamsters were entrained to eight different T-cycles (1 hr of light per cycle), released into DD, and given a phase delaying light pulse 7 days later. T-cycles which entrained the animals so that the 1 hr of light fell between 6 and 9 hours after the onset of activity suppressed the amplitude of phase delays, whereas T cycles which entrained the animals so that the 1 hr of light fell at other times did not suppress phase delays. The implications of the data for entrainment theory and the mechanism of action of the tau gene are discussed. PMID- 7873777 TI - The biosynthesis of rhizobial lipo-oligosaccharide nodulation signal molecules. AB - While a great deal has been learned concerning the biosynthesis of Nod factors, there is much that remains to be determined. The functions of many Nod proteins involved in adding the host-specific modifications to the Nod factors remain to be unequivocally identified. Some of the genes required for these modifications have not yet been isolated, e.g., those involved in carbamylation, or addition of D-Ara. Additionally the cellular location of most of the Nod proteins and, concomitantly, the modifications they determine are not known. The actual in vivo substrates for the NodABC proteins have not been identified, and the enzyme activities of purified NodA and NodC have not been demonstrated. The synthesis and export of the Nod factors most probably involves some type of carrier/anchor which remains unidentified. Analysis of GlcNAc metabolites from various mutants, e.g., nodA-, nodB-, or nodC- mutants, should facilitate the identification of the in vivo substrates involved in the synthesis of the "common" Nod factor and, thereby, lead to a greater understanding of Nod factor biosynthesis and transport. Finally, comparison of Nod factor biosynthesis to other examples of polysaccharide or glycolipid biosynthetic pathways suggest that several key enzymes remain to be identified. It is hoped that this discussion will be helpful in designing strategies for the detection and isolation of such novel enzymes. PMID- 7873778 TI - Identification of a novel Rhizobium meliloti nodulation efficiency nfe gene homolog of Agrobacterium ornithine cyclodeaminase. AB - The nfe genes located on the large plasmid pRmeGR4b are involved in the nodulation efficiency and competitiveness of Rhizobium meliloti GR4 on alfalfa roots. One hundred twenty-eight base-pairs downstream of nfe2 gene we found an open reading frame designated ORFC, 970 bp long and potentially coding for a 320 amino acid long protein. The amino acid sequence of the putatively encoded ORFC product shows similarity with ornithine cyclodeaminase (OCD) of Agrobacterium tumefaciens an unusual enzyme that converts ornithine into proline. The gene product of ORFC was identified as a 37-kDa protein by in vitro-coupled transcription-translation and in vivo by the T7 RNA polymerase/promoter system. DNA hybridization studies showed that strain GR4 carries a single copy of the ocd like gene. No homologous sequences to GR4 ORFC DNA were found in other R. meliloti strains or Rhizobium spp. assayed. Furthermore, a GR4 derivative mutant obtained by plasmid disruption of ORFC showed an impaired nodulation efficiency as compared to that of the wild-type strain GR4. Thus, the former locus should be considered a novel nfe gene. We propose to rename the nfe genes, nfe1, 2 and ORFC as nfeA, B, and D, respectively. PMID- 7873780 TI - The regulation of exopolysaccharide production is important at two levels of nodule development in Rhizobium meliloti. AB - We show that two exopolysaccharide overproducing Tn5 mutants of Rhizobium meliloti, exoR and exoS, have distinct symbiotic defects. While the exoR mutant is unable to colonize nodules, the exoS mutant retains that ability but varies in its ability to produce nitrogen-fixing nodules. We correlate these defects with different degrees of exopolysaccharide overproduction and growth impairment. We further show that the exoR mutant is able to enter developing infection threads but is unable to invade nodule cells. The exoR mutant gives rise to spontaneous pseudorevertants containing second-site suppressor mutations that decrease exopolysaccharide synthesis. These pseudorevertants form nitrogen-fixing nodules. Although the suppressor mutations have the opposite effect on exopolysaccharide production compared to the exoS::Tn5 mutation, they consistently map to the exoS::Tn5 region and belong to the same genetic complementation group as defined by transposon insertion mutations. The effect of the suppressor mutations on exopolysaccharide production is correlated with effects on the expression of exo genes involved in exopolysaccharide synthesis. Finally, we provide evidence that the exoR gene is not required for the regulation of exopolysaccharide synthesis by ammonia. PMID- 7873779 TI - Characterization of avrPphE, a gene for cultivar-specific avirulence from Pseudomonas syringae pv. phaseolicola which is physically linked to hrpY, a new hrp gene identified in the halo-blight bacterium. AB - The avirulence gene matching the R2 gene for resistance to halo-blight disease in Phaseolus was cloned and sequenced from race 4 strain 1302A of Pseudomonas syringae pv. phaseolicola. The predicted 41-kDa AvrPphE protein is hydrophilic, has no features that indicate function, and no similarity to other protein sequences. The promoter region of avrPphE contains a "harp box" motif. The gene was expressed more strongly in minimal than in nutrient-rich media. Lower concentrations of the phytoalexin phaseollin accumulated in tissue undergoing the hypersensitive reaction (HR) determined by avrPphE than by avrPphB. Homologs of avrPphE were detected in strains representing eight races of P. s. pv. phaseolicola including those virulent on cultivars with the R2 resistance gene, and in P. s. pv. tabaci but not in P. cichorii or P. s. pvs. coronafaciens, glycinea, maculicola, pisi, or syringae. Disruption of avrPphE prevented induction of the HR but did not appear to affect basic pathogenicity. Transposon mutagenesis and DNA sequencing showed that avrPphE was linked to hrpY a hrp locus identified at the left end of the hrp gene cluster. Sequence analysis showed that the region linked to avrPphE was very similar to DNA containing hrp genes from P. s. pv. syringae including hrpJ, hrpL, and hrpK. PMID- 7873781 TI - Genetic variation in homothallic and hyphal swelling isolates of Pythium ultimum var. ultimum and P. utlimum var. sporangiferum. AB - Genetic variation in a collection of 22 Pythium ultimum isolates was analyzed using restriction fragment length polymorphisms (RFLPs), random amplified polymorphic DNA (RAPD), and sequence characterized amplified regions (SCARs) as genetic markers. Qualitative evidence for the occurrence of sexual outcrossing in the field, asexual mechanisms affecting variation, and differences in aggressiveness between isolates was found. Codominant SCAR and RFLP markers detected multiple alleles in several isolates. Genetic analysis of F1 progeny from a cross indicates that heterozygosity is one cause of multiple alleles and contributes to genetic variation. Segregation analysis of F2 progeny fit diploid expectations and supported the use of the molecular markers for phenetic analysis. One isolate contained three alleles at one locus suggesting that polyploidy, aneuploidy or heterokaryosis may also contribute to genetic variation. Phenetic analysis using UPGMA clustering of Nei's distance calculated from RFLP data, UPGMA clustering of similarity matrixes calculated from RAPD data, and principle component analysis of RAPD data revealed no clustering of the three morphological types of Pythium ultimum (var. ultimum, var. sporangiferum, and group HS). Our results suggest that the three morphological variants of this homothallic oomycete are not genetically distinct. PMID- 7873782 TI - Acquisition and transmission of Agrobacterium by the whitefly Bemisia tabaci. AB - Whiteflies transmit many different plant pathogens. We show here that the whitefly Bemisia tabaci can also acquire Agrobacterium tumefaciens from liquid cultures and from crown galls, and transmit it to plants. Cloned tomato yellow leaf curl virus (TYLCV) DNA and A. tumefaciens tumor-inducing functions were used as reporter genes. Whiteflies were fed through membranes on cultures of Agrobacterium At::pTY4 containing a dimeric copy of an infectious TYLCV genomic clone between the T-DNA borders of a binary vector. One hour of feeding was sufficient for the insects to be able to transmit TYLCV to tomato test plants. Infectious Agrobacterium was recovered from whiteflies that fed on At::pTY4 cultures, indicating that bacteria was acquired and remained intact in the insects. Whiteflies also acquired the virulent A. tumefaciens strain C58 from crown galls and induced tumors in tomato test plants. PCR and Southern blot analyses indicated that the target plant tissues were transformed. These results show that an insect can transfer foreign genes to plants by acquiring and delivering transforming bacteria. PMID- 7873783 TI - AVRXa10 protein is in the cytoplasm of Xanthomonas oryzae pv. oryzae. AB - AVRXa10 from Xanthomonas oryzae pv. oryzae was tagged with a unique hydrophilic octapeptide (FLAG) to permit antibody-mediated identification and purification of the gene product. X. o. pv. oryzae that produced tagged AVRXa10 elicited a hypersensitive response (HR) on rice cultivars containing the resistance gene Xa 10, but not on cultivars lacking Xa-10. The tagged AVRXa10 protein purified from Escherichia coli or X. o. pv. oryzae did not elicit a hypersensitive response in rice with the Xa-10 resistance gene. Anti-FLAG monoclonal antibodies reacted with a 119-kDa protein in both E. coli and X. o. pv. oryzae cells expressing the tagged avrXa10 gene. Polyclonal antibodies raised against purified AVRXa10 protein reacted with the 119-kDa protein and several additional proteins from X. o. pv. oryzae, which probably are the products of genes related to avrXa10. Biochemical fractionation and immunoelectronmicroscopy analysis was used to demonstrate that AVRXa10 was located in the cytoplasm of X. o. pv. oryzae cells when grown in planta or in culture medium. PMID- 7873784 TI - Alpha v integrin subunit is predominantly located in nervous tissue and skeletal muscle during mouse development. AB - Alpha v integrin subunit can dimerize with different beta subunits to form receptors for several matrix proteins. The function of these receptors in vivo is still largely unknown. We examined the localization of alpha v integrin during mouse development and showed that its distribution is dynamically regulated in the glia of the central nervous system and in skeletal muscle. Immunoreactivity in the neural tube was firstly localized at embryonic day 10.5 (E10.5) around cell bodies lining the lumen and along tiny fibres extending towards the outer margin. At E12.5 alpha v distribution follows the highly defined pattern of the radial glia: fascicles of immunoreactive fibres form parallel palisades, in particular along the hindbrain and the spinal cord. At E15.5, although with weaker intensity, alpha v was still detectable in radial glia fibres, and it codistributed with glial fibrillary acidic protein positive fascicles. After birth (P8) alpha v immunoreactivity in the brain and spinal cord decreased dramatically, but remained high in the radial glia of the cerebellum. In adult mice alpha v reactivity in the central nervous system disappeared. During myogenesis alpha v appears at E10.5 in myotomal cells and from E12.5 alpha v was evident in myoblasts and in myotubes. In the developing skeletal muscle of E15.5 embryos, immunoreactivity became more concentrated in the apical portion of the myotubes. In adult striated muscle the amount of alpha v subunit dramatically declined and immunostaining was no longer detectable. During development, alpha v was weakly evident in other sites including heart and endothelia of blood vessels, mesonephric tubula, smooth muscle of the digestive tract, and bronchia. Comparative analysis of the localization of alpha v, alpha 3, and alpha 5 integrin subunits indicated that alpha v has a unique and highly regulated distribution pattern. The distribution in the nervous system is consistent with a role of alpha v in neuron-glia interaction during the organization of the neuronal layers in the brain cortex and in the cerebellum. Moreover, alpha v is likely to be involved in the myotendinous junction during embryonic life, suggesting a dual functional role of this integrin in muscle and nervous tissue. PMID- 7873785 TI - Structure and distribution of N-cadherin in developing zebrafish embryos: morphogenetic effects of ectopic over-expression. AB - N-cadherin cDNA was cloned from a zebrafish embryonic cDNA library. Analysis of the deduced amino acid sequence of this molecule (ZN-cadherin) revealed a high degree of homology to N-cadherins of other species, except that its pre-sequence is considerably shorter. Nevertheless, following transfection into chinese hamster ovary (CHO) cells, the expressed protein was functionally active, namely participated in calcium-dependent intercellular interactions. Moreover, ectopic over-expression of ZN-cadherin, following mRNA microinjection into 2-4 cell embryos, caused microaggregation and uneven segregation of deep cells, resulting in distorted embryos. Developmental Northern and Western blot analyses indicated that both the mRNA and the protein first appear at gastrulation. In-situ hybridization showed that ZN-cadherin mRNA was initially present in all deep cells, and later became restricted to various epithelial and neural tissues. Whole-mount immunostaining indicated that while ZN-cadherin was already present at 50% epiboly, it became associated with cell junctions only 4-5 h later. In developing somites ZN-cadherin expression was prominent but transient. High levels of the protein were detected in epithelial somites and its expression was apparently down regulated concomitantly with the onset of myogenesis. PMID- 7873786 TI - Tumor necrosis factor-alpha and embryonic mouse lung morphogenesis. AB - The ontogeny of the embryonic and fetal lung involves complex interactions between epithelial and mesenchymal primordia which require a specific program of gene regulation and signal transduction. Past studies in our laboratory using congenic mouse strains indicate that one or more genes which map to the H-2 region of chromosome 17 regulate the rate of lung morphogenesis, defined in this context as differentiative heterochrony among strains. Since hormones and growth factors are the messengers of morphogenesis, it was logical to propose that tumor necrosis factor-alpha (TNF-alpha), a well-characterized cytokine whose gene maps to the D-region of the H-2 complex, is a putative mediator of lung morphogenesis. We investigated this proposition using immunochemical methods and a serumless, chemically defined in vitro model system. Our results demonstrate that: (1) TNF alpha has a specific spatiotemporal localization, in vivo and in vitro; (2) TNF alpha receptor, in vivo and in vitro, is localized throughout the embryonic lung; (3) TNF-alpha supplementation in vitro of embryonic lung primordia has a marked dose-dependent, stimulatory effect on branching morphogenesis and surfactant associated protein (SP-A) expression; (4) multiple immunoreactive proteins, including 17, 26, and 68 kDa species, are expressed during development in vivo, and a subset of these are expressed in vitro; and (5) both time- and glucocorticoid-dependent changes occur in the in vivo expression pattern of TNF alpha immunoreactive proteins after 4 and 7 days in vitro, including the up regulation of a novel 40 kDa protein. Given that glucocorticoids (CORT) regulate TNF-alpha expression and TNF-alpha's ability to stimulate pulmonary morphodifferentiation and histodifferentiation, we conclude that TNF-alpha is an autocrine/paracrine pulmonary cytokine, probably a component of the lung morphogenesis pathway regulated by CORT. PMID- 7873787 TI - Patterns of cell behaviour underlying somitogenesis and notochord formation in intact vertebrate embryos. AB - We have made a detailed analysis of cell behaviour using high resolution time lapse microscopy of the earliest cellular interactions taking place during morphogenesis of the notochord and somites in intact teleost embryos. Notochord formation is typified by active intercalation of paraxial mesenchyme cells into the lateral surfaces of the primordium. Following this recruitment phase, complete immiscibility develops between cells of the notochord and the presomitic mesenchyme. Dorso-ventral and rostro-caudal expansion of the notochord is characterised by translocation of cells within dorso-ventral planes of section and is supported by elongation of the remaining cells and reduction in width across its latero-medial axis. A lateral palisading of paraxial mesenchyme against the lateral aspects of the notochord precedes overt segmentation. Intersomitic furrows form by localised de-adhesion at small foci at the nascent intersomitic planes, which are consolidated by coalescence of such areas by de adhesion to produce the interface. It is not possible to predict precisely where cells would initiate de-adhesion since there is a stochastic element to the phenomenon. Once formed, boundaries between somites are stable and provide no opportunity for mixing, except across the first formed furrow, which disintegrates at the 4-6 somite stage. The first ten somites form at a constant rate of 2.3 somites/hr, during which time we recorded constant relative displacement of the segmental plate against the rostro-caudally elongating notochord. Unlike teleost epiboly and gastrulation, no large-scale movements of individual cells can be detected during elaboration of the embryonic axis. PMID- 7873788 TI - Expression patterns of the bone morphogenetic protein genes Bmp-4 and Bmp-2 in the developing chick face suggest a role in outgrowth of the primordia. AB - Bone morphogenetic proteins BMP-4 and BMP-2 are closely-related members of the transforming growth factor-beta superfamily that have been implicated in signalling in a number of developmental systems. To determine whether they could be involved in the epithelial-mesenchymal interactions that control face development, we mapped the distribution of Bmp-4 and Bmp-2 gene transcripts in the developing chick facial primordia. At stages when primordia were becoming established, Bmp-4 transcripts were present in specific regions of epithelium in all facial primordia, but were undetectable in the mesenchyme. Bmp-4 transcripts appeared subsequently in specific regions of mesenchyme at the distal tips of the primordia. This mesenchymal expression first appeared in the frontonasal mass and then, in turn, in the lateral nasal processes, the maxillary primordia and the mandibular primordia. There was a complex relationship between domains of epithelial and mesenchymal Bmp-4 expression, and at many sites there was an inverse correlation between epithelial and mesenchymal Bmp-4 expression. Bmp-2 transcripts were found in the epithelium and mesenchyme of the maxillary and mandibular primordia at early stages in facial development. Bmp-2 transcripts appeared in the frontonasal mass and lateral nasal processes at later stages, with epithelial expression preceding mesenchymal expression. In general, mesenchymal Bmp-2 expression was associated with overlying epithelial Bmp-2 expression. The domains of Bmp-4 expression overlapped with those of Bmp-2, but detailed examination showed that there was no precise correlation between the expression patterns of the two genes. Indeed, in some places the Bmp-4 and Bmp-2 expression domains were complementary. The expression of the Bmp-4 and Bmp-2 genes in the epithelium and distal mesenchyme of the facial primordia suggests that BMP-4 and BMP-2 may be involved in the epithelial-mesenchymal interactions that control outgrowth of these primordia. PMID- 7873789 TI - Differential expression during embryogenesis of three genes clustered in the Ras1 region of Drosophila melanogaster. AB - Transcription mapping and nucleotide sequence analysis reveal that the genomic region of the Drosophila Ras1 gene contains a cluster of three closely localized genes. A gene termed Rlb1 is located nearby and upstream of Ras1, and is oriented in the opposite polarity relative to Ras1. In addition, a third gene termed Rlc1, is found at a very close proximity downstream to Rlb1. Ras1, the homologue of the human transforming ras genes, has been shown to be active in the posterior termini of the Drosophila embryo and in the eye imaginal disc in pathways of cell fate determination. We demonstrate that during embryogenesis Ras1 transcripts are restricted mainly to the embryonic central nervous system, suggesting that the gene product also may have a role in these nerve cells. Rlb1 encodes for a novel, lysine-rich basic protein. It is expressed mainly in the developing midgut and in the somatic mesoderm. Rlc1 also encodes for a novel, basic protein. The expression of Rlc1 during embryogenesis is similar, but not identical, to the expression pattern detected for Ras1. The vertebrate p21Ras proteins are bound to the inner face of the cell membrane. Ras1, the Drosophila homologue of p21, and the Rlb1 protein, are also non-cytoplasmic, membranous proteins. Rlb1 is found in the cell membrane of larval midgut epithelial cells. In addition, Rlb1 is detected in the nuclei of these cells, and in the nuclei of the midgut imaginal cells. PMID- 7873790 TI - Developmental relations between sixth nerve motor neurons and their targets in the chick embryo. AB - The developmental relations between abducens (VI) nerves and their targets, the lateral rectus, quadratus, and pyramidalis muscles, have been examined in the chick embryo from early neural tube stages through 10 days of incubation. Sites of myoblast origins were determined by microinjection of replication-incompetent retroviruses containing the LacZ reporter into paraxial mesoderm corresponding to somitomeres 3-5. Motor neurons and axons were identified by Bodian staining, immunocytochemistry, and application of DiI and DiO to dissected peripheral nerves. Anlage of the dorsal oblique originate in somitomere 3, close to the ventrolateral margin of the mid-to-caudal mesencephalon. Precursors of the lateral rectus arise deep within somitomere 4, beside the future metencephalon (rhombomere "A"). Quadratus and pyramidalis precursors are located between and partially segregated from these other two anlage. VIth nerve axons exit rhombomeres 5 and 6 via multiple median roots, fasciculate, and by stage 17 have elongated rostrally beneath the hindbrain. Immediately caudal to a mesenchymal pre-muscle condensation located deep to rhombomere 2, the VIth nerve separates into two branches. One branch enters the rostral portion of the condensation, from which quadratus and pyramidalis muscles will segregate. This branch projects exclusively from rhombomere 5 and is the accessory abducens nerve. The other branch enters the caudal, presumptive lateral rectus, region of the condensation. This is the abducens nerve, and it projects from cells located in both rhombomeres 5 and 6. These findings indicate that specific matching of motor nerves with their presumptive targets begins prior to the differentiation and segregation of myogenic populations, and that spatial organization of developing eye muscles is initiated well before they interact with connective tissue precursors derived from the neural crest. PMID- 7873791 TI - Differentiation potentialities of distinct myogenic cell precursors in avian embryos. AB - Interspecific grafting experiments between chick and quail embryos were carried out to investigate the differentiation capacities of myoblasts from different development stages. Grafts consisted of 3.5-day-old embryonic quail dermomyotomes isolated from the cranial level, 7- to 10-day-old and 16-day-old embryonic quail pectoralis muscles, 15-day-old postnatal quail pectoralis muscle, and 3- to 10 day-old embryonic quail cardiac and gut muscles. Grafts were implanted into 2-day old chick embryos in place of the dorsal halves of somites from the prospective wing level. After implantation of dermomyotome fragments, we observed that quail cells participated in trunk and limb musculature. After implantation of 7- to 10 day-old embryonic muscle, quail cells were rarely found in the limb but systematically took part in the formation of trunk muscles. All these capacities were totally lost in 16-day-old embryonic and 15-day-old postnatal muscles. After implantation of nonsomitic derivatives such as embryonic cardiac and gut muscles, implanted cells never participated either in wing or trunk musculature. After dermomyotome, embryonic muscle, and gut implantation, quail cells were capable of invading the dermis and aggregating into feather germs. Our results extend those previously reported and indicate that somitic myogenic derivatives which do not migrate in the normal course of embryogenesis have migratory potentialities and are able to give rise to axial muscles. All these potentialities are lost as myogenesis proceeds in embryos. PMID- 7873792 TI - Morphological characteristics of boar efferent ductules and epididymal duct. AB - The aim of the present study was to provide a comprehensive morphological analysis of the porcine epididymis in view of the specific functions being performed in different regions of this organ. Blood supply and microvasculature of efferent ductules and epididymal duct were investigated by means of corrosion casts which were analysed macroscopically and by scanning electron microscopy. This revealed blood supply to the testis and epididymis to be closely related. The capillary pattern was typical for the efferent ductules, the caput, corpus, and distal cauda epididymidis, respectively. Corrosion casts were also used to visualize the course of the efferent ductules themselves. Tissue samples from different regions of the efferent ductules and epididymal duct were examined by light microscopy and both scanning and transmission electron microscopy, with special attention being payed to transitional areas. Morphological criteria allowed the distinction of three segments within the efferent ductules and of the initial segment, proximal caput, distal caput, corpus, proximal cauda, and distal cauda regions of the epididymal duct. Components of the endocytic apparatus of efferent ductule principal cells were identified by ferritin uptake. Ultrastructural evidence of absorption in the epididymal duct was particularly prominent in proximal and distal caput. Extensive cisternae of rough endoplasmic reticulum and a well-developed Golgi apparatus were indicative of active protein synthesis and secretion especially in the distal caput and corpus regions. However, assignment of various organelles in principal cells of the epididymal duct to either absorptive or secretory pathways still remains tentative. PMID- 7873793 TI - Structure and function of the ductuli efferentes: a review. PMID- 7873794 TI - Sulfated glycoprotein-2 synthesized by nonciliated cells of the efferent ducts is targeted to the lysosomal compartment. AB - The epithelial nonciliated cells of the efferent ducts are specialized in internalizing many luminal substances. The nonciliated cells actively endocytose sulfated glycoprotein-2 (SGP-2), a major secretory protein of Sertoli cells and a homologue of human apolipoprotein J. This study was undertaken to investigate the internalization of Sertoli-derived SGP-2 and synthesis of an endogenous efferent duct form of SGP-2 by nonciliated cells targeted to their secondary lysosomes on animals whose efferent ducts were ligated and/or received injections of tunicamycin. The regulation of synthesis of the endogenous form of SGP-2 within nonciliated cells by hormones in general and testosterone in particular was also examined using hypophysectomized and castrated animals with or without subsequent testosterone replacement. Quantitative electron microscope immunocytochemistry was performed on groups of animals fixed with 4% paraformaldehyde and 0.5% glutaraldehyde in phosphate buffer for each experimental condition and their controls. In each case, the labeling density (number of gold particles/micron 2) within the endosomal (endosomes) and lysosomal (dense multivesicular bodies and secondary lysosomes) compartments was calculated. The results revealed that ligation of the efferent ducts resulted in a significant decrease in the labeling density of the endosomal and lysosomal compartments. However, a baseline of about 18% of controls was still observed in the lysosomal compartment 24 h after ligation. In this compartment similar values were noted 24 h after tunicamycin treatment in conjunction with or without ligation. These results suggest that an endogenous form of SGP-2 is synthesized by nonciliated cells and presumably targeted via small vesicles from the Golgi apparatus to the lysosomal compartment, but that the major portion of SGP-2 within this compartment is derived via endocytosis of testicular SGP-2. Hypophysectomy and castration also showed significant decreases in the labeling densities of these two compartments, but again a baseline level of labeling was noted in the lysosomal compartment. Subsequent testosterone administration to 7-day hypophysectomized or castrated animals had no effect on the labeling density of the lysosomal compartment, as values comparable to the effect of hypophysectomy or castration alone were noted. Taken together these results suggest that the nonciliated cells of the efferent ducts synthesize an endogenous form of SGP-2 that is targeted to the lysosomal compartment and which is not regulated by pituitary factors or testosterone. PMID- 7873795 TI - Two Golgi integral membrane proteins (GIMPS) exhibit region- and cell type specific distribution in the epididymis of the adult rat. AB - The epididymis participates in the post-testicular maturation and storage of spermatozoa by secreting proteins into the tubule lumen in a region-specific fashion. The underlying molecular mechanisms leading to biogenesis of these region-specific differences, however, are not known, although components of the Golgi complex membrane container must undoubtedly be intimately involved. Two monoclonal antibodies raised against Golgi integral membrane proteins, recognizing either the cis (GIMPc) or trans Golgi (GIMPt) cisternae, were used as molecular probes of these regions to begin the characterization of the Golgi complex of in vivo and in vitro epididymal cells. Immunolocalization of GIMPs was performed on frozen sections and in cultured cells using biotin-streptavidin peroxidase immunocytochemistry. In tissue sections, immunostaining of GIMPt was extremely robust in the supranuclear cytoplasm throughout the epididymis. In contrast, no GIMPc immunostaining was detected in the initial segment or in clear cells of the distal caput, corpus, and cauda. Immunodetection of GIMPc and GIMPt in epididymal cells in vitro revealed a reticular, perinuclear pattern, and NH4Cl treatment preferentially disrupted the GIMPt immunolocalization. These results characterizing the molecular components of the Golgi complex will form the basis of additional studies to gain further insight into mechanisms leading to generation of regional differences in epididymal function. PMID- 7873796 TI - Origin and development of the muscles of the intermetacarpal space of the forelimb of Felis catus. AB - This paper demonstrates the structure and development of the layer of mm. flexores breves profundi in Felis catus (Carnivora). By microdissections of the deep palmar musculature, it was found that there were formed two muscle layers: 1) four muscles beginning on the palmar side of the carpus, passing distally through the intermetacarpal spaces and inserting into the dorsal digital aponeurosis of the second to fourth digit--the superficial muscle layer of mm. flexores breves profundi; 2) four muscles beginning on the palmar area of the second to fifth metacarpus and inserting into the capsules of the metacarpophalangeal joints of the second to fifth digit--the deep muscle layer of mm. flexores breves profundi. Ontogenesis of these muscle layers was studied on 35 histological series of embryonal extremities. In early ontogenesis we found a coherent cell condensate of the anlage of mm. flexores breves profundi layer. Differentiation of the anlagen of individual muscles takes place in the foetuses of 17-20 mm crown-rump length. In embryos of 17-19 mm crown-rump length a small cell condensations corresponding to the layer of mm. intermetacarpales anlagen were found in the second and third intermetacarpal spaces. Both anlagen are formed only temporarily whereafter they break into fragments and extinct. PMID- 7873797 TI - Musculi contrahentes in the ontogenesis of the cat limb. AB - This paper demonstrates the structure and development of the layer of mm. contrahentes in Felis catus (Carnivora). Ontogenesis of the muscle layer was studied on 35 histological series of embryonal extremities and by microdissections of palmar musculature in the domestic cat. It was found that three mm. contrahentes were formed passing to the first, second and fifth digits. A compact anlage of the muscle layer (similar to that in embryos of many mammalian species) has been observed only in foetuses of 15-16 mm crown-rump length. Differentiation of the anlagen of the individual muscles takes place in the foetuses of 20-23 mm crown-rump length. PMID- 7873798 TI - The vomeronasal system of the mink, Mustela vison. I. The vomeronasal organ. AB - The vomeronasal organ (VNO) of the mink is restricted to the area of the Fissura palatina and thus always topographically related to the Ductus incisivus (DI). The VNO and DI have also a functional relation because the vomeronasal duct ends in the incisive duct. On the other hand, as the DI has its mouth in the Papilla incisiva there is a communication between the VNO and the oral cavity. The vomeronasal cartilage, approximately in 1/6 of its length, wraps completely the parenchyma of the VNO whose main structure is the vomeronasal duct, with two different epithelia: sensory receptor in the medial wall, and respiratory in the lateral one. Nevertheless the variations of epithelia belong to the segment of the duct because in its rostral and caudal parts the medial and lateral epithelia are very similar. Branches and tubular PAS positive glands stand out in three points: superior, inferior and medial areas of the vomeronasal duct in which they end. An important number of vessels, mainly veins of different diameter, are located around the duct, while the nervous fibers are close to the medial wall of the duct and very easy to identify in the caudal third of the organ. Two immunohistochemical techniques were used to identify the nerve fibers and the receptor cells. PMID- 7873799 TI - Anatrecon: a user guide to software package for computer-aided three-dimensional reconstructions. AB - "Anatrecon" is an original Czech software package. It enables one to make easy three-dimensional reconstructions from serial sections of cells and tissues. It offers very acceptable information on the three-dimensional structure and especially on mutual relationships of biological objects in such cases when other methodical approaches, e.g., scanning electron microscopy or laser scanning confocal light microscopy, cannot be applied. The program runs on a standard IBM compatible personal computer supplemented with a digitizing tablet. The author describes the program in detail and presents examples of reconstructions of dendritic spine and nucleus of nerve cell. PMID- 7873800 TI - The effect of actinomycin D on the megakaryocytic line in rat. AB - Four-day administration of actinomycin D to the albino rat in daily doses of 25 micrograms/kg decreased--in relation to all blood cells of the bone marrow--the values of the more mature stages of the megakaryocytic line, i.e. megakaryocytes and naked megakaryocyte nuclei. The number of megakaryoblasts was not influenced. PMID- 7873801 TI - Indirect maternal effects of oxacillin administered to pregnant mice on the postnatal immune response of the offspring. AB - Effects of oxacillin administered to pregnant or nursing randombred NMRI mice on the humoral immune response of their offspring were studied. The primary humoral response of male offspring to immunization by sheep red blood cells (SRBC) on the 24th postnatal day was assayed. Spectrophotometric determination of SRBC lysis by anti-SRBC IgM antibodies produced by spleen cells was used. Treatment of pregnant mice with oxacillin (70 mg/kg body weight) from the 12th to 16th day of pregnancy resulted in an enhancement of the spleen IgM antibody response in their offspring. The same treatment of nursing mothers, either on postnatal days 1-4 or 13-16, depressed the humoral response of the offspring. When the litters of control mothers and mothers treated with oxacillin from the 11th to 15th day of pregnancy were cross-fostered at birth, the offspring born of saline-treated mothers and nursed by oxacillin-treated mothers as well as the offspring born to oxacillin-treated mothers and nursed by control mothers produced significantly higher amounts of spleen anti-SRBC IgM than the control offspring. The results suggest that the alteration of the immune response in offspring of mice treated by oxacillin during pregnancy was induced not only in the prenatal period, but also postnatally by factors originating from effects of oxacillin on the maternal organism. PMID- 7873802 TI - rRNA synthesis in proerythroblasts and hepatocytes after cyclosporin A administration in chick embryo. AB - The ribosomal RNA (rRNA) synthesis in the proerythroblasts and hepatocytes of the chick embryo was examined using the nucleolar test during embryonic days 5-10 after intraamniotic administration of single doses of cyclosporin A (CsA). Administration of the 0.75 or 7.5 g of CsA 5th day of embryonic development caused a significant decrease in proerythroblasts and hepatocytes numbers with active rRNA synthesis. Five days after the CsA administration, the percentage of proerythroblasts with biosynthetically active nucleoli already did not differ from the control while the decreased numbers of hepatocytes actively synthetizing rRNA remained statistically significant. Our results indicate, that CsA inhibits the rRNA biosynthesis in embryonic immature cells. Depending on the cell type, the effect of CsA and its dynamics may be apparently different. PMID- 7873803 TI - Localization of basic and acidic argyrophilic proteins in nuclear structures of elongating mouse spermatids. AB - Different cytochemical techniques at the electron microscopic level were used to investigate the presence of basic and acidic proteins during spermiogenesis in mice. Basic lysine rich proteins were demonstrated with an ethanolic solution of phosphotungstic acid, acidic agryrophilic proteins using two silver staining procedures applied en bloc and on the ultrathin lowicryl sections. Both types of proteins had very similar localization in the nucleoplasm and identical distribution within the postacrosomal dense lamina on the surface of late spermatid heads. The specificity of reactions is briefly discussed. PMID- 7873804 TI - Differing embryotoxic effects of senecionine and senecionine-N-oxide on the chick embryo. AB - The embryotoxic properties of pyrrolizidine alkaloids senecionine (water insoluble) and senecionine-N-oxide (water soluble) were examined using the CHEST method (Chick Embryotoxicity Screening Test). The beginning of the embryotoxicity range for senecionine was found to be between 3-30 micrograms; senecionine-N oxide, on the other hand, showed no effect even with 100 micrograms dose. On the basis of the theoretical calculation, it can be expected that senecionine embryotoxicity for mammals ranges between 10-100 mg/kg maternal body weight, overlapping in this way the known adult toxicity range. The rat LD50 of most alkaloids known to be significant for human health are in the range of 34-300 mg/kg. PMID- 7873805 TI - Confined placental mosaicism and uniparental disomy. PMID- 7873806 TI - Ontogenesis of the vascular bed in the human skeletal muscles. AB - The ontogenetic development of the vascular bed was studied in the muscles of human fetuses after India ink and gelatine injections. By the 12th week of intrauterine life the architectural arrangement of the largest (primary) intra muscular vessels is qualitatively comparable with that of the adult muscles. The smaller (secondary) vessels, as well as the microcirculatory bed, have very immature features in all fetal muscles studied. This part of the vascular bed develops gradually during further time from a primitive intramuscular capillary network. The basic architectural arrangement of the microcirculatory bed in adult muscles, and the development of the structure of the hilar vessels of the gastrocnemius muscle were described in the muscles of fetuses, newborns, and adults. PMID- 7873807 TI - The Rhode Island Hearing Assessment Program. PMID- 7873808 TI - Varicella vaccine for prevention of chickenpox. AB - Release of varicella vaccine is anticipated in early 1995. The vaccine has proved to be safe and effective in clinical trials over the past 12 years. Proposed recommendations for use include a single dose for routine vaccination of 12 to 18 month-old infants and for catch-up immunization of children from 18 months to 12 years of age and a two dose schedule to immunize susceptible adolescents and adults. PMID- 7873809 TI - Kawasaki syndrome: diagnosis and management. PMID- 7873810 TI - Recent advances in pediatrics and neonatology. PMID- 7873811 TI - Childhood lead poisoning. AB - Lead poisoning has been referred to as the most important environmental health hazard for children in New England. Medical professionals are in a unique position to perform a number of interventions that could make a lasting impact. First, physicians and nurses, particularly in the areas of pediatrics and family medicine, can provide anticipatory guidance to all families with young children. Lead poisoning, in contrast to long held beliefs, is an affliction that affects all socioeconomic groups. Parents should thus be informed regarding sources of lead, including occupational and hobby sources, and basic nutritional and abatement information should be provided. Second, health care workers should encourage lead screening in appropriately aged children at recommended intervals based on known risk factors. Once a blood lead concentration greater than 20[symbol: see text]g/dl has been obtained in a child, treatment or referral to an established lead clinic should be undertaken in a timely fashion. For children with low or moderate lead levels, many pediatricians or family physicians prefer to supervise their patients' treatment, including chelation therapy. For children with higher levels or in instances when the health care professional elects to refer, there are several lead clinics throughout New England whose clinicians are experienced in the treatment of childhood lead poisoning. Finally the medical profession needs to publicly recognize, as child advocates, that lead poisoning is one of the most common pediatric health problems in the United States and that it is entirely preventable. Fortunately, after many years and much hard work, Rhode Island finally has laws that start to deal with the lead problem in an appropriately aggressive fashion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873812 TI - The seductive poppy. PMID- 7873813 TI - Alcohol-related mortality in Rhode Island, 1986-1990. PMID- 7873814 TI - Exogenous surfactant in neonatal respiratory distress syndrome. PMID- 7873815 TI - Possible nutritional factors in induced pemphigus. AB - Today it is generally accepted that every drug that possesses an active thiol group in its molecule is capable of inducing pemphigus. Some plants, in particular those belonging to the Allium group, contain several active compounds with stable disulfide and thiol groups in their molecule. The Allium group contains many important vegetables like onion, leek and garlic. Examples of molecules with an active thiol group are: CH2 = CH-CH2-S-S-CH2-CH = CH2 (diallyl disulfide) or CH2 = CH-CH2-S(O)S-CH2-CH = CH2 (allicin). It is suggested that some foods, in particular vegetables of the Allium group that contain active thiol groups in their molecule, could contribute to the induction of pemphigus. In general, nutritional factors should be added to the list of exogenous factors that are capable of inducing pemphigus. PMID- 7873816 TI - The heterogeneity of the germinative compartment in human epidermis and its implications in pathogenesis. AB - In mouse epidermis keratinocytes of the basal layer seem to belong to 3 different subpopulations: stem cells, transit cells and postmitotic cells. Each subpopulation assumes a specific role in epidermal homeostasis. Recent data tend to display a similar heterogeneity among basal keratinocytes in human epidermis. This concept opens the door to an integrated understanding of epidermal renewal but also suggests new hypotheses in pathogenesis. Psoriasis, a typical example of epidermal hyperplasia, is considered from this point of view. PMID- 7873817 TI - Delayed hypersensitivity to Propionibacterium acnes in patients with severe nodular acne and acne fulminans. AB - BACKGROUND: Increased hypersensitivity reactions to Propionibacterium acnes may be involved in the pathogenesis of severe acne. OBJECTIVE: To study delayed and immediate hypersensitivity reactions to P. acnes in patients with severe nodular acne (SNA) and acne fulminans (AF). METHODS: We performed lymphocyte stimulation and skin tests for P. acnes antigens on 11 patients with SNA and 7 patients with AF. RESULTS: The patients with SNA had similar mean lymphocyte stimulation indices (mean 13.96, SD 8.6) to P. acnes during active disease as had healthy controls (12.63, SD 6.46). After the treatment the mean stimulation index was significantly elevated (23.47, SD 13.84, p = 0.006). A similar increase occurred in the patients with AF (mean 17.04, SD 5.74, and 33.42, SD 27.17, respectively). Two of 7 patients with SNA and 3 of the 7 patients with AF but none of the 10 control subjects showed positive 48-hour intradermal tests to P. acnes. CONCLUSION: Specific cell-mediated immunity to P. acnes increases during the course of severe inflammatory acne. PMID- 7873818 TI - Normal-range plasma catecholamines in patients with generalized and acrofacial vitiligo: preliminary report. AB - BACKGROUND: There is a body of evidence that neutral factors may play a role in the pathogenesis of vitiligo. OBJECTIVE: We look for the existence of a relationship between vitiligo and monoaminergic systems. METHODS: We use high pressure liquid chromatography to measure the plasma level of catecholamines, their precursor 3,4-dihydroxyphenylalanine and their metabolites 3-methoxy-4 hydroxy phenylglycol (MHPG), normetanephrine (NMN), metanephrine and homovanillic acid (HVA). Forty patients with the generalized (n = 31) and acrofacial (n = 9) types of vitiligo are studied. RESULTS: Significant differences are not found either between males and females or between the entire group of patients and the controls. HVA and NMN levels significantly correlate with age (r = 0.332, p < 0.05, and r = 0.331, p < 0.05, respectively). Significant correlations are also seen either between noradrenergic or between dopaminergic parameters (norepinephrine vs. MHPG, r = 0.326, p < 0.05; dopamine vs. HVA, r = 0.540, p < 0.01). When the patients are grouped on the basis of vitiligo type or age of disease onset, the plasma mean levels of the neural compounds are always nonsignificantly different from those of the controls. However, both catecholamines and metabolites show higher, although not significant, concentrations in patients with a shorter duration of disease. CONCLUSION: Monoaminergic systems seem unlikely to be related to vitiligo, at least to the generalized and acrofacial types. However, variations cannot be excluded in genetically predisposed individuals during the onset or the active phases of disease. PMID- 7873819 TI - Proliferative activity of epidermal and dermal T lymphocytes in mycosis fungoides. AB - BACKGROUND: Mycosis fungoides (MF) is histologically characterized by an accumulation of T lymphocytes (T cells) in both epidermis and dermis. However, the mechanism of the formation of Pautrier's microabscess or the maintenance of the epidermal T cells has not yet been clarified. OBJECTIVE: The rate of proliferation of these T cells was investigated. METHODS: The formalin-fixed, paraffin-embedded sections from 9 cases of patch/plaque stage MF were immunostained with proliferating cell nuclear antigen (PCNA). RESULTS: The PCNA positive T cell nuclei were found both in the epidermis (including Pautrier's microabscesses) and dermis in all the specimens. The mean PCNA indices of the T cells were 20.2 +/- 10.6% (mean +/- SD) within the epidermis and 16.8 +/- 6.5% in the dermis, which was not statistically significantly different (p > 0.05). The ratio of the PCNA index between the epidermis and dermis was 1.3 +/- 0.6, which was not apparently correlated with the duration of the disease (8.4 +/- 5.1 years). CONCLUSION: These findings suggested that in situ proliferation might contribute to the epidermal T cell population resulting in the formation of Pautrier's microabscesses and an increase in dermal T cell volume during the course of the disease. PMID- 7873820 TI - Interleukin-6 and tumour necrosis factor levels decrease in the suction blister fluids of psoriatic patients during effective therapy. AB - BACKGROUND: Involvement of various cytokines in psoriasis pathomechanisms has previously been reported. OBJECTIVE: To better define the relationship between the disease severity and interleukin-6 and tumour necrosis factor alpha skin levels, these two cytokines were measured in suction blister fluids obtained from involved and uninvolved skin areas of psoriatic patients treated with UVB, beta methasone dipropionate and salicylic acid ointment. METHODS: Determinations were performed by ELISA in fluids obtained from 6 patients with the Kiistala method, every 1-2 weeks for at least 1 month. RESULTS: During the observation period, all the patients showed disease improvement (median PASI score declined from 13.4 to 3.9) and significant decreases in the cytokine levels in all samples. CONCLUSION: These results are in agreement with a functional involvement of these two cytokines in the pathogenesis of the disease and their possible use as follow-up markers. PMID- 7873821 TI - The development of non-melanocytic skin cancers in people with a history of skin cancer. AB - OBJECTIVE: To determine the incidence of new skin cancer formation in people who have had skin cancer removed. STUDY DESIGN: A prospective study of Melbourne out patients with histologically confirmed non-melanoma skin cancer (NMSC). All patients with NMSC seen by one author (D.C.) between November 1988 and November 1989 were entered into the study and reviewed regularly. New skin cancers were removed and recorded. RESULTS: Four hundred and eighty-one patients were entered and 420 followed for at least 3 years. New NMSC developed in 60% (adjusted for losses) by the end of 3 years. A multivariate analysis determined that the main risk factor for new NMSC formation was the number of previous skin cancers that a patient had. Those who had had multiple skin cancers (3 or more) were at significantly greater risk than those with less than 3. Age, sex and type of NMSC were not risk factors for new skin cancer formation. CONCLUSION: Patients with NMSC require long-term follow-up because of the risk of new skin cancer formation. Those with multiple NMSC need more careful follow-up, and possibly more frequent examinations, because they are at greater risk. PMID- 7873822 TI - Papular elastorrhexis: a variant of dermatofibrosis lenticularis disseminata (Buschke-Ollendorff syndrome)? AB - BACKGROUND: Buschke-Ollendorff syndrome is an autosomal dominant disorder clinically characterized by the appearance of disseminated white papules and osteopoikilosis. Histologically most cases show normal collagen and increased elastic tissue. Abortive forms of Buschke-Ollendorff syndrome are described, which show characteristic skin involvement, absence of skeletal changes and decreased elastic tissue. Papular elastorrhexis is characterized by nonfollicular, white papules, decreased elastic tissue, no genetic inheritance and no osteopoikilosis. OBJECTIVE: Is papular elastorrhexis a new entity or an abortive form of Buschke-Ollendorff syndrome? METHODS: We examined three members of one family (brother, sister and mother) presenting with nonfollicular, distributed, white papules on the trunk and extremities. Skin biopsies were examined by histological and electron-microscopic methods. RESULTS: The histological and electron-microscopic examinations of skin biopsies showed decreased, fragmented elastic fibers and normal collagen. By X-ray examination, no osteopoikilosis was found. The family presented here supports a genetic background of the disease. CONCLUSION: The clinical appearance with the absence of osteopoikilosis and the histological findings of our cases suggest the diagnosis of papular elastorrhexis. Papular elastorrhexis however was reported to be nonfamilial. Because of the genetic background found here we believe that papular elastorrhexis is an abortive form of Buschke-Ollendorff syndrome. Summarizing our data and reviewing the literature, we suggest that connective tissue nevi with the most prominent alterations in the elastic tissue should be classified under the term elastic tissue nevi. PMID- 7873823 TI - Pastes: what do they contain? How do they work? AB - BACKGROUND: Pastes are semisolid stiff preparations containing a high proportion of finely powdered material. Powders such as zinc oxide, titanium dioxide, starch, kaolin or talc are incorporated in high concentrations into a preferably lipophilic, greasy vehicle. A clinically distinctive feature which is generally attributed to pastes is the quality to absorb exudates by nature of the powder or other absorptive components. Reviewing the various pharmacopoeias serious doubts arise from the various formulas of pastes and their absorptive features. The zinc oxide pastes of the USP XXII, the DAB 10 and BP 88 (US, German and British pharmacopoeias). are composed of petrolatum, zinc oxide and starch. Petrolatum, a highly lipophilic, water-immiscible vehicle surrounds the powder particles preventing any absorption of water or exudates. OBJECTIVE: The goal of our investigation was to test a simple experimental setting to characterize the clinically important absorptive feature of powders and pastes. METHODS: The absorptive features of the powders were determined by the method of Enslin. The absorptive features of the paste preparations were calculated from the weight difference between the paste preparation before and after incubation with water using a simple standardized procedure. RESULTS: The absorptive features of titanium dioxide, zinc oxide, kaolin, corn starch and methylcellulose powder in pharmacopoeia quality were determined. Zinc oxide and kaolin powder showed the highest absorption of 1,000 mg water/g powder (100%). The water absorption of corn starch and titanium dioxide was 700 and 450 mg/g powder, respectively. The absorptive features of a series of paste preparations were studied in a simple experimental setting. The data show that two-phase pastes consisting of two immiscible components, one (the dispersed or inner phase; powder) being suspended in the other (the continuous or outer phase; lipophilic vehicle), have no absorptive features. In contrast, three-phase pastes consisting of a hydrophilic two-phase emulsion with high concentrations of incorporated powder (cream pastes) show considerable water uptake. CONCLUSIONS: We conclude that the classical two phase pastes such as the zinc oxide pastes have no absorptive features. On the contrary, these formulations are highly occlusive. Therefore lipophilic pastes are only indicated when protection of intact skin against aggressive body exudates and humidity is required. The hydrophilic three-phase pastes or cream pastes show considerable water uptake and fulfil common expectations of pastes to dry the skin. PMID- 7873824 TI - Clinical experience with short schedules of itraconazole in the treatment of tinea corporis and/or tinea cruris. AB - BACKGROUND: Superficial fungal infections have usually been considered to be caused only by dermatophytes. In recent years their epidemiology has been changing with other fungi being isolated and, thus, antifungal agents with a broad spectrum of activity, such as itraconazole, may be particularly useful. The risk/benefit ratio for any such treatment is determined by its tolerability profile and the duration of therapy. OBJECTIVE: The aim was to compare the efficacy and tolerance of a shorter treatment regimen, using a higher dose of itraconazole, with a standard itraconazole regimen in the treatment of tinea corporis/cruris. METHODS: An open study compared oral itraconazole 200 mg daily for 7 days with oral itraconazole 100 mg for 15 days in 153 patients with tinea corporis/cruris. RESULTS: At follow-up all patients in both groups were clinically cured or markedly improved. However, mycological cures were greater in the 7-day treatment group (90%), and the onset of clinical and mycological cure was faster in this group. CONCLUSIONS: Itraconazole, 200 mg daily for 7 days, offers a short convenient and effective treatment option for tinea corporis and tinea cruris. PMID- 7873825 TI - Evolution of a naevus spilus. AB - The evolution of a naevus spilus is documented with serial photographs over a 12 year period. The lesion was remarkable for increasing numbers of macules and papules within the background of the cafe-au-lait macule. Biopsy of a new papule showed lentiginous melanocytic hyperplasia without atypia. We advise photography and periodic follow-up of large, clinically atypical or changing naevi spili. Indications for considering biopsy of naevi spili, irrespective of size, include atypical clinical features or change in one of the hyperpigmented macules or papules, eventuating in an atypical clinical appearance. PMID- 7873826 TI - Progressive hyperpigmentation: case report with a clinical, histological, and ultrastructural investigation. AB - A clinical, histological and ultrastructural study of a 38-year-old woman with generalized progressive hyperpigmentation is reported. Hyperpigmentation started in early infancy, progressed during childhood and has increased to a dark bronze brown color with 'mottling' in the last 8 years. Histology and electron microscopy revealed epidermal hypermelanosis and 'negroid' distribution of melanosomes in keratinocytes. In our family, autosomal dominant phenotype transmission with 'variable expression' is suggested. The literature on the entity has been reviewed. This case is another rare example of familial progressive hyperpigmentation. PMID- 7873827 TI - Proteus syndrome. AB - Proteus syndrome is a rare hamartomatous syndrome with a variety of abnormalities. A 6-year-old Japanese boy without apparent abnormalities at birth developed by 1 year of age cerebriform skin tumors on the right sole, soft masses on the left sole, palms and fingers, brownish verrucous lesions and whorled brownish patches on the right side of the neck, chest, external genitals and extremities, hemihypertrophy of the right lower extremity, lordoscoliosis, protuberance of the skull, epileptic seizures, hydrocephalus and mental retardation. This patient appears to be the second Japanese case of Proteus syndrome. PMID- 7873828 TI - Molluscum contagiosum mimicking sebaceous nevus of Jadassohn, ecthyma and giant condylomata acuminata in HIV-infected patients. AB - We report on three HIV-infected homosexual male patients with atypical manifestations of mollusca contagiosa (MC). Their clinical presentation mimicked sebaceous nevus of Jadassohn, ecthyma and giant condylomata acuminata. HIV infected patients feature MC with atypical morphology in about two thirds of the cases. The atypical aspects of MC concern the localization, morphology, growth pattern and size of the lesions. MC is a late manifestation of HIV infection and mirrors marked cellular immune deficiency. We conclude that in HIV-infected patients all tumorous lesions should be biopsied because the clinical characteristics are often not specific enough for a definite diagnosis. PMID- 7873829 TI - Localized scleroderma after exposure to organic solvents. AB - A 26-year-old female developed plaques characteristic of morphea on the volar surfaces of the forearms and on the dorsal surfaces on the ankles following an exposure to trichloroethylene, tetrachloroethylene and other solvents by inhalation. Exposure to chemicals has been known to be important as a provoking factor of systemic sclerosis. This patient shows that exposure to solvents could provoke localized scleroderma. PMID- 7873830 TI - Spironolactone-associated cutaneous effects: a case report and a review of the literature. AB - Spironolactone therapy is uncommonly associated with cutaneous side effects. We describe a patient who developed a maculopapular eruption while on spironolactone with a positive reaction upon rechallenge with the drug. The cutaneous associations of spironolactone in the English literature have been reviewed. PMID- 7873831 TI - Secondary pancreatic involvement of mycosis fungoides detected by a clinically palpable mass. AB - A patient with a 4-year history of mycosis fungoides, who presented a pancreatic spreading of the disease, detected by a clinically palpable mass, is reported and discussed with a review of the literature. Mycosis fungoides (MF) is a T cell lymphoma primarily localized to the skin. Laparoscopic staging and autopsy studies, however, have shown that lymph node involvement or visceral spreading is common in the course of the disease [1-3]. Among visceral manifestations of MF, pancreas infiltration is found in 20-40% of autopsied cases [1, 2, 4]. Occurrence of a palpable pancreatic mass has never been described. We report a patient with a long-standing MF, and a secondary pancreatic extension detected by a palpable mass. PMID- 7873832 TI - Parakeratosis pustulosa with dyskeratotic cells. PMID- 7873833 TI - Skin diseases induced by other skin diseases: the boomerang phenomenon. PMID- 7873834 TI - Topical haemotherapy for leg ulcers. AB - Several growth factors, present in the plasma or delivered by blood cells, are involved in wound healing. We have treated 15 chronic atonic leg ulcers by topical application of autologous heparinized blood under a hydrocolloidal dressing. This 'topical haemotherapy' (THT) was applied every other day. After the first THT, 30% of the fibrinonecrotic material had already been removed. After a mean of 9 THT applications (range: 5-18), granulation tissue covered up to 75% of the surface of the ulcer (range: 30-100%) allowing autologous skin grafting. No local or systemic side-effects occurred during the treatment. THT is feasible and well tolerated; it is an easy and inexpensive treatment of chronic leg ulcers that rapidly induces granulation tissue. Growth factors and proteases produced by the blood cells could play a relevant role in this process. PMID- 7873835 TI - Livedo racemosa: a report of five cases. AB - We present 5 patients in whom the diagnosis of livedo racemosa gave rise to clinical and laboratory investigations revealing arterial disease of different etiologies. This presentation emphasizes the importance of not missing the clinical diagnosis of livedo racemosa. PMID- 7873836 TI - The association of the two antimalarials chloroquine and quinacrine for treatment resistant chronic and subacute cutaneous lupus erythematosus. AB - Antimalarials are the first line in the treatment of chronic and subacute cutaneous lupus erythematosus (LE). However, some patients show either no or only minor improvement on antimalarial monotherapy. We treated 14 patients (9 with chronic LE and 5 with subacute cutaneous LE) who had poorly responded to chloroquine or hydroxychloroquine with an association of chloroquine and quinacrine. The initial dose was: chloroquine 100 mg 3x/day and quinacrine 65 mg 3x/day. The skin lesions improved significantly or cleared totally in 5 of the 9 patients with chronic LE and in all the 5 patients with subacute cutaneous LE. These findings suggest that a chloroquine-quinacrine combination may sometimes be superior to the usual antimalarial monotherapy, especially for subacute LE. If chloroquine or hydroxychloroquine fails to control chronic or subacute cutaneous LE, chloroquine-quinacrine is worthy to be tried. PMID- 7873837 TI - Hydroa vacciniforme. AB - Hydroa vacciniforme is a rare chronic photodermatosis with onset in childhood. It is characterized by recurrent vesicles healing with scars. We report a typical case of a young, 8-year-old boy showing favorable evolution under treatment with chloroquine and a topical sunscreen. PMID- 7873838 TI - Acrodermatitis chronica atrophicans involving the face. Evidence for Borrelia burgdorferi infection confirmed by DNA amplification. AB - In a female patient with increasing redness of the hands and face, proteins of Borrelia burgdorferi were detected in a biopsy of the ear by DNA amplification. Although acrodermatitis chronica atrophicans has been documented to be caused by B. burgdorferi, this is the first case with proven spirochetal presence in the skin of the head. After 2 weeks of intravenous therapy with ceftriaxone marked improvement of discoloration of the skin was noted. PMID- 7873839 TI - Necrotizing vascular calcinosis. AB - The case of a 62-year-old woman with end-stage renal failure who developed necrotizing vascular calcinosis is reported. Histologically, classical vascular calcinosis of arterioles with fibrosis of the intima were found in the subcutis and in the deep dermis. PMID- 7873840 TI - The petrified ear. AB - A case of an otherwise healthy 66-year-old male with bilateral symmetric ossification of his ears is described. The rare occurrence of petrified ears is emphasized, and possible etiologic factors are discussed. No other explanation than anamnestic prolonged exposure to hypothermia was found. PMID- 7873841 TI - Eruptive hamartomatous clear-cell acanthomas. AB - This is a report on a 38-year-old female, suffering from over 100 solid papules arising on her legs, arms and trunk during the past 10 years. The histology shows the typical feature of clear-cell acanthoma (CCA). Extensive investigations did not reveal any extracutaneous abnormalities. This case is exceptional because of the high number of hamartomatous CCA which exceeds the maximal number of about 20 seen in multiple CCA so far and therefore is referred to as eruptive hamartomatous CCA. PMID- 7873842 TI - Cotrel-Dubousset instrumentation and thoracolumbar spine trauma: a review of 55 cases. AB - A series of 55 patients treated with posterior Cotrel-Dubousset instrumentation and osteosynthesis for unstable thoracolumbar spine fractures were reviewed. Follow-up averaged 48.3 months. The fractures were all unstable, with 27 classified as fracture-dislocations (FD) and 28 classified as flexion compression injuries or unstable burst fractures (FC/B). The study population was composed of 29 men and 26 women with an average age of 31 (range 20-45) years. Mechanisms of injuries included 35 motor vehicle accidents, 19 falls, and one blunt trauma. No case worsened as a result of surgery, and 31% of the cases improved an average of 0.5 Frankel grade (range 0-2). Sixty percent of patients were braced with a custom molded thoracolumbosacral orthosis (TLSO) fitted after surgical stabilization. Minor complications occurred in 45% of the cases (urinary tract infection most common). There was a singular deep wound infection and another iliac crest donor site infection. There were no instrument failures or pseudarthroses. Radiographic analysis showed the following improvements in fracture angle, vertebral body compression, and fracture displacement. The pattern of radiographic improvement in the FD and FC/B subgroups showed significant improvement in each parameter when comparing preoperative to immediate postoperative values. Of importance, the radiographic findings comparing 1 month to the final follow-up showed little to no deterioration. Cotrel-Dubousset instrumentation proved to be a highly effective device for immediate restabilization of unstable thoracolumbar injuries. PMID- 7873843 TI - Recurrent disk versus scar in the postoperative patient: the role of computed tomography (CT)/diskography and CT/myelography. AB - The purpose of this study was to compare computed tomography (CT)/myelography and CT/diskography images, in a given patient, as a method of distinguishing postoperative fibrosis from recurrent herniated disk material. The study population consisted of 20 patients who had undergone lumbar diskectomy and subsequently developed recurrent radicular pain. All patients underwent CT/myelography and CT/diskography, each procedure performed within 72 h of the other. Comparison of transaxial images from CT/myelography and CT/diskography at a given disk space level yielded the following results: in 12 patients the extradural mass seen via CT/myelography corresponded entirely to the contrast filled disk fragment seen via CT/diskography (recurrent herniated disk); in three patients the extradural mass seen via CT/myelography was larger than the disk fragment seen via CT/diskography (recurrent herniated disk and fibrosis); and in five patients CT/diskography images appeared normal, but CT/myelography showed an extradural mass (fibrosis). Fifteen patients underwent surgical reexploration with the following results: in three of three patients, the suspicion of recurrent herniated disk and fibrosis by radiologic evaluation was confirmed by surgical reexploration; in nine of 12 patients, solely recurrent herniated disk shown by radiologic criteria was similarly confirmed. The remaining five patients presumed to have fibrosis by radiologic criteria were treated nonoperatively. PMID- 7873844 TI - Use of titanium implants in pedicular screw fixation. AB - Several types of pedicular screw systems have been utilized to augment lumbar spine fusion. All systems are made of stainless steel, which interferes with imaging techniques, especially MRI and CT scans. In search of a solution for this problem, we decided to study the use of titanium systems in the lumbar spine. Because there were no titanium pedicle screw systems available on the market, we decided to use the titanium Alta system currently used for femur fractures. This report details our experience in using this device for lumbar spine fusion. From 1990 to 1992, 25 patients underwent thoracic and lumbar fusion with Alta titanium screws and plates. Spinal fusion was performed for a variety of conditions, including metastatic tumor, fracture, spondylolisthesis, pseudoarthrosis, and postdecompressive instability. All but two patients obtained solid fusion clinically and radiographically and considerable improvement in back pain. There was loosening of the implant in both patients. Both patients had osteoporosis. One of these two patients developed pseudoarthrosis, which required further surgery. The other patient with a metastatic tumor of the spine remained asymptomatic without change in the spine alignment despite progression of the tumor. There were no broken screws encountered during follow-up. Two patients sustained subsequent fracture of the vertebra above the fusion. One of the patients also developed a fracture below the fusion. Fusion with titanium implants allowed postoperative evaluation and subsequent periodic examination of the spinal canal with high-quality MR images as well as significant reduction of artifacts on CT scan.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873845 TI - Lumbar disc space heights after external fixation and anterior interbody fusion: a prospective 2-year follow-up of clinical and radiographic results. AB - Forty-two consecutive patients with severe spine problems were tested by temporary external fixation of the lower lumbar spine. Twenty-nine experienced marked relief of pain and were subjected to anterior interbody fusion. In 27 cases the scheduled clinical and radiographic 2-year follow-up could be completed. Disc height was measured on radiographs taken before the test, during the test with disc space distraction, after the anterior fusion, and 1 and 2 years postoperatively. The Oswestry disability score and the visual analog scale (VAS) for back and leg pain were also recorded. The 2-year clinical results were judged excellent in nine cases, good in ten, fair in three, and poor in five. Ten patients had a nonunion. Mean disc space height increased with external fixation and anterior interbody fusion but returned to the preoperative level during follow-up. These changes in disc space height did not statistically correlate with the clinical results or the occurrence of nonunion. A statistically significantly better clinical outcome, however, was found in patients with solid fusion than in patients with nonunion. PMID- 7873846 TI - Embryological study of the spinal ligaments in human fetuses. AB - We studied embryological development of the human spinal ligaments by dissecting 25 fetuses that ranged from 6 to 24 weeks of gestational age. At 6 and 7 weeks, the spine consisted of light zones and dark zones. The light zones were hypocellular and corresponded to vertebral bodies. The dark zones were hypercellular and corresponded to intervertebral disks. The anterior longitudinal ligament was identified at the gestational age of 8 weeks. At 10 weeks, the posterior longitudinal ligament was detected. At 12 weeks, laminae, the ligamentum flavum, and an ossification center were identified. At 15 weeks, fibers of the ligamentum flavum became clearer, but they were not as well as stained as the adult ligamentum flavum. The enthesis of the ligaments in the human fetuses was not completely identical to that in adults. PMID- 7873847 TI - Comparison of anterior cervical fusions using autogenous bone graft obtained from the cervical vertebrae to the modified Smith-Robinson technique. AB - Anterior cervical discectomy and interbody grafting provide excellent results in treating cervical radiculopathy. This prospective study compares the results of the technique obtaining autogenous bone from the cervical vertebrae for grafting to the modified Smith-Robinson technique using autogenous iliac crest graft. Seven levels in six patients were fused using the vertebral body autograft technique and 43 levels in 40 patients using the standard technique. All patients had radiculopathy and neck pain. Statistically significant differences in fusion rate (4/7 vertebral body autograft; 40/43 modified Smith-Robinson) (p = 0.029), disc height maintenance (p = 0.001), and neck pain improvement (p = 0.05) occurred between the techniques. We do not recommend vertebral body autograft over the modified Smith-Robinson technique for anterior cervical fusion following discectomy. PMID- 7873848 TI - Study of low-temperature thermoplastic modified custom-molded cervical orthosis for cervical spine fixation. AB - The purpose of this experiment is to use a low-temperature thermoplastic material (Aquaplast) to make a modified custom-molded cervical orthosis. Sixteen normal young subjects who do not have previous cervical problems are tested in this study. This modified orthosis is applied on these volunteers so that external fixation of the cervical spine can be tested. Various roentgenograms for cervical flexion and extension, as well as neutral position and lateral bending, are taken to determine the fixation property of the cervical spine. A study of rotation of the cervical spine is also carried out through goniometer measurements. This clinical study proves that this low-temperature thermoplastic cervical orthosis provides good fixation for the cervical spine, especially in flexion and rotation, but is not suitable for C1- and C2-injured patients. PMID- 7873849 TI - Nerve root complications of percutaneous laser-assisted diskectomy performed at outside institutions: a technical note. AB - Two patients, treated with percutaneous laser-assisted diskectomy, developed postoperative nerve root complications. The first patient, whose diskectomy had been performed by a gastroenterologist, suffered an acute foot drop that resolved following delayed surgical diskectomy, whereas the second patient's L4 and L5 root deficits remained permanent. Percutaneous laser-assisted diskectomy, by reducing intradiscal volume, is considered an alternative to open surgery in the management of contained lumbar disc herniations. After an L4-L5 diskectomy and a fenestration procedure performed 2 months later for a sequestrated disc herniation and segmental stenosis, the first patient's foot drop resolved. Unfortunately, the second patient's L4 and L5 root injuries, without MRI and myelo-CT surgical pathology, were complete. The laser-assisted diskectomy may produce reversible and irreversible nerve root injuries. PMID- 7873850 TI - Cervical radiculomyelopathy due to deposition of calcium pyrophosphate dihydrate crystals in the ligamentum flavum: historical and histological evaluation of attendant inflammation. AB - Deposition of calcium pyrophosphate dihydrate (CPPD) crystals in the yellow ligament occasionally leads to neurological deficits through compression of the spinal cord. Although it is widely accepted that CPPD crystal induces severe inflammation in arthropathy, little attention has been paid to the acute inflammation that may accompany the CPPD crystals in the ligamentum flavum. The present study reviews eight patients with radiculomyelopathy due to calcification of the cervical yellow ligament. Acute inflammation of the yellow ligament accompanying the crystalline deposits, both with and without attendant granulation tissue-proliferation, was evaluated as contributing to cervical radiculomyelopathy. Three cases with attendant granulation tissue suffered from recurrent attacks of neck pain and fever with coincidental radicular pain in the upper arm. The local inflammation of the ligamentum flavum might have participated in the exacerbation of the cervical radiculopathy. PMID- 7873851 TI - Complete atlanto-axial dislocation associated with type II odontoid fracture: a report of two cases. AB - Two cases of complete atlanto-axial dislocation with associated Type II odontoid fracture are reported. In one case, the instability associated with this injury was treated with primary odontoid fixation. In the second case, the patient had full cardiac arrest associated with this injury. Due to the extreme instability present with this fracture sub-type and the potential for neurological compromise, early recognition of this fracture pattern by the treating physician is imperative to prevent fatal spinal cord injury. PMID- 7873852 TI - Scoliosis secondary to rib resection. AB - The case histories of 11 patients (five adults and six children) who presented with scoliosis after multiple rib resection for several disorders were reviewed. All 11 cases developed scoliosis with the convexity directed toward the side of the rib resection. The natural history of the scoliosis was progressive, and the younger the age at the time of rib resection, the more severe the progression. The rate of progression was greatest during the first 10 years after rib resection. The five patients who presented as adults were treated in several ways, only one requiring spine fusion. However, five of the six children required spine fusion to prevent progression of scoliosis. PMID- 7873853 TI - Ganglioneuroma of the thoracic spine presenting as adolescent idiopathic scoliosis: a case report. AB - Ganglioneuromas are rare soft-tissue tumors that can present as painless spinal deformities. The surgical outcome is usually satisfactory when complete excision is achieved. A case of spinal ganglioneuroma presenting as adolescent idiopathic scoliosis is presented to illustrate the illusive nature of this condition. PMID- 7873854 TI - Cystic lesion of the second cervical vertebral body. Case report. PMID- 7873855 TI - Canine model of acute aortic rupture: treatment with percutaneous delivery of a covered Z stent--work in progress. AB - PURPOSE: To develop a percutaneous treatment for aortic rupture with use of a covered intraluminal stent. MATERIALS AND METHODS: A transmural tear was created percutaneously in the thoracic aorta in six dogs with use of a 4-mm angioplasty balloon. Gianturco Z stents were covered with polytetrafluoroethylene, loaded into a 14-F sheath, and advanced through the femoral artery to the site of injury. Within 2 minutes after initiation of the injury, the stent was deployed. Homologous canine blood was given during the procedure. Dogs that survived 24 hours were then killed. RESULTS: The first stent did not expand completely, and the dog died in 1 hour. At necropsy, the first two dogs (1-hour and 8-hour survival) had a large left hemothorax and extensive periaortic hematoma, indicating intrathoracic exsanguination. The next four dogs were treated with a modified stent and survived 2 hours (n = 1), 8 hours (n = 1), and 24 hours (n = 2). At necropsy hemothorax did not exceed 15 mL, and periaortic hematomas were small. The cause of death in the two early casualties with the modified stent is uncertain. There were no signs of spinal cord injury despite occlusion of three pairs of intercostal arteries. CONCLUSION: The covered Z stent (in its modified form) tamponaded the aortic tear, preventing exsanguination. Long-term studies of biocompatibility of this device appear justified. PMID- 7873856 TI - Treatment of aortic dissections with a percutaneous intravascular endoprosthesis: comparison of covered and bare stents. AB - PURPOSE: The authors developed a percutaneous endoprosthesis for treatment of aortic dissections. The device is a Gianturco stent wrapped with Dacron or nylon mesh. Effectiveness of the covered stent versus a bare stent was compared in the treatment of acute aortic dissection. MATERIALS AND METHODS: Experimental aortic dissections were created in 10 mongrel dogs. Occlusion of intimal tears was attempted with covered stents in five dogs (group 1) and with bare stents in the remaining five dogs (group 2). RESULTS: In group 1, entry tears were obliterated within 1 day (n = 3) or 1 week (n = 2) after stent placement and false lumina were thrombosed within 1 week (n = 3) or 1 month (n = 2). In group 2, entry tears and false lumina remained patent. Histologic specimens showed that the covered stents were entirely covered with smooth neointima. CONCLUSIONS: This endoprosthesis offers an alternative to surgical treatment for dissections of the descending aorta. PMID- 7873857 TI - Hydrodynamic thrombectomy of hemodialysis fistulas: first clinical results. AB - PURPOSE: A hydrodynamic thrombectomy system was used for the treatment of recent dialysis shunt thrombosis. PATIENTS AND METHODS: Sixteen shunt thromboses in 14 patients were included in the study. There were seven polytetrafluoroethylene grafts and nine native arteriovenous fistulas. Occlusion time ranged from 6 to 48 hours, and thrombus length ranged from 4 to 40 cm. RESULTS: Thrombectomy was technically successful in 15 of 16 instances. No significant residual thrombus was found in 15 cases. In one case, half of the thrombus remained in the vessel and the procedure failed technically. One embolus to the radial artery occurred after balloon dilation following hydrodynamic thrombectomy and was removed percutaneously. Early rethrombosis within 24 hours occurred in five shunts; four more rethrombosed within 2 weeks to 3 months. Eleven shunts were available for follow-up. Cumulative patency was 41% after 6 months. CONCLUSION: Hydrodynamic thrombectomy is a promising concept for declotting of both hemodialysis grafts and native shunts and may offer an alternative to thrombolysis and surgical thrombectomy. PMID- 7873858 TI - In vivo evaluation of the Hydrolyser hydrodynamic thrombectomy catheter. AB - PURPOSE: The authors evaluated a 7-F double-lumen thrombectomy catheter (Hydrolyser) in vivo. MATERIALS AND METHODS: To evaluate efficacy, thrombectomy was performed 1, 4, or 8 days after local denudation in peripheral arteries (n = 18) and veins (n = 29) of nine goats. To evaluate safety, the reaction of the vessel wall to a functioning and nonfunctioning Hydrolyser catheter was evaluated in the peripheral arteries and veins of three goats 10 days after the procedure. RESULTS: Reopening was achieved in all vessels with residual thrombus in 11% of arteries (two of 18) and 55% of veins (16 of 29). Slight intimal thickening was observed, but no difference was seen between the passage of a functioning versus nonfunctioning catheter. CONCLUSIONS: The Hydrolyser device can remove intravascular thrombus up to 8 days after induction. There was no difference in vessel wall reaction after the passage of a functioning and nonfunctioning catheter. PMID- 7873859 TI - Creation of a stenotic stent to reduce flow through a transjugular intrahepatic portosystemic shunt. PMID- 7873860 TI - Fatal hemodynamic consequences of therapeutic closure of a transjugular intrahepatic portosystemic shunt. PMID- 7873861 TI - Fine-needle transjugular portal venous access system. PMID- 7873862 TI - Embolized portal vein catheter fragment in a liver transplant recipient: intraoperative removal using a snare. PMID- 7873863 TI - Chronic iliac artery occlusions: primary recanalization with endovascular stents. AB - PURPOSE: The authors describe treatment of chronic iliac artery occlusions with primary stent placement without prior thrombolysis or angioplasty. PATIENTS AND METHODS: Eight patients with chronic iliac artery occlusions (six men and two women) underwent primary stent placement without prior use of thrombolytic agents or angioplasty. Palmaz stents were placed in seven patients and a Wallstent device was placed in one. RESULTS: In all patients, revascularization was successful without residual stenoses or pressure gradients. There was no angiographic evidence of distal embolization. CONCLUSION: Primary stent placement for chronic iliac artery occlusions without prior thrombolysis or angioplasty appears to be safe and efficacious and is potentially cost effective. PMID- 7873864 TI - Renal artery stent placement: immediate and midterm technical and clinical results. AB - PURPOSE: The authors report their experience with implantation of self-expandable stents into renal arteries. PATIENTS AND METHODS: Twenty-five Wallstent endoprostheses were deployed into 18 renal arteries in 18 patients. Atheroma was the cause of the initial renal artery lesion in 15 patients (four ostial, 10 postostial, and one long occlusion). In these 15 patients, indications for stent placement were 12 immediate failures of percutaneous transluminal renal angioplasty (PTRA), two immediate PTRA complications (dissections), and one recurrent stenosis. The other renal artery lesions were three dissections (two spontaneous and one after catheterization). RESULTS: The procedure was technically successful in all patients, with residual stenosis less than 20%. However, five stents were slightly misplaced and a second stent was implanted to fully cover the lesion. Three complications occurred: one acute thrombosis 15 days after stent implantation that was successfully treated with local fibrinolysis, one asymptomatic occlusion due to early thrombosis or to delayed restenosis, and one segmental renal infarction related to extensive dissection after PTRA and not to stent placement. Following stent implantation, systolic blood pressure (P = .006) and diastolic blood pressure (P = .002) measured at 6 months decreased significantly. Angiographic follow-up was obtained in 16 patients (with intravenous technique in nine and intraarterial digital subtraction angiography in seven) at a mean of 11 months after stent placement, and ultrasonographic follow-up was obtained in the two others after 8 and 25 months, respectively. A normal patent renal artery was demonstrated in 16 patients (89%); there was one restenosis with a 75% reduction in diameter of the renal artery and the asymptomatic occlusion above mentioned. CONCLUSION: Self expandable stent implantation is a promising technique in PTRA failures. Wallstent placement is technically feasible. Immediate results were satisfactory and the midterm restenosis rate was low in this series of patients. PMID- 7873865 TI - Percutaneous placement of a Hickman catheter with use of an intercostal vein for access. PMID- 7873866 TI - Preliminary clinical experience with the Gunther temporary inferior vena cava filter. AB - PURPOSE: The authors describe their preliminary clinical experience with the Gunther temporary inferior vena cava (IVC) filter. PATIENTS AND METHODS: Seven women and 10 men, mean age 52 years (range, 19-85 years), were treated with the temporary IVC filter. Indications for filter placement were pulmonary embolism (PE) in four patients and iliofemoral deep venous thrombosis in six. In these patients anticoagulation was contraindicated because of planned major surgery. Filters were placed in four patients following massive PE and in three for prophylaxis following cranial trauma. Four patients had underlying malignant disease. Filters were introduced through the right common femoral vein in 14 patients, the left common femoral vein in two, and the left internal jugular vein in one. RESULTS: No patient developed recurrent PE with the filter in place. All filters were removed without complication 3-14 days (mean, 7 days) after placement. Two of the patients with underlying malignant disease required placement of a permanent filter. Two patients developed IVC thrombosis with the filter in place, and both developed recurrent PE after filter removal. Two patients developed insertion vein thrombosis. One patient developed a bleeding disorder that caused a massive hematoma at the insertion vein site, which may have contributed to her death. CONCLUSION: The Gunther temporary filter can be used in selected patients; however, patients with underlying malignant disease may be more appropriately treated with a permanent filter. The temporary filter does not appear to reduce the rate of insertion vein and IVC thrombosis. PMID- 7873867 TI - In vitro evaluation of vena cava filters. AB - PURPOSE: The authors tested in vitro nine caval filters to evaluate clot-trapping capacity and transfilter pressure gradients under varying experimental conditions. MATERIAL AND METHODS: The filtering efficiency of the stainless-steel Greenfield filter was evaluated in a modified flow model. A total of 2,100 clots were injected. In addition, controlled parameters simulating in vivo conditions were selected to appreciate clot-trapping capacity and pressure gradients for nine filters in horizontal and vertical positions, by using small (3 x 30 mm) and medium-sized (5 x 30 mm) clots. Statistical evaluation was performed for 3,600 clot deliveries. RESULTS: Depending on experimental conditions, the clot-trapping capacity of the Greenfield filter varied greatly (0%-78%) by using small and medium clots. Bird's Nest and Simon nitinol filters demonstrated the highest filtering efficiency (94%-100%) for small clots. Medium clots were effectively captured by Bird's Nest, Simon nitinol, Antheor, and Gunther Tulip filters (79% 100%). CONCLUSION: Experimental parameters influence a filter's clot-trapping capacity. Bird's Nest filters demonstrated the highest clot-trapping capacity. PMID- 7873868 TI - Improved mechanical thrombolysis with the addition of recombinant tissue-type plasminogen activator: in vitro study with use of Cr-51-labeled clots. AB - PURPOSE: To explore the potential effect of infusion of recombinant tissue-type plasminogen activator (rt-PA) during mechanical thrombolysis. MATERIALS AND METHODS: Clots containing chromium-51-labeled platelets produced from blood from two donors were placed in a solution of rt-PA (1.25 micrograms/mL) or in saline solution and were pulverized with a mechanical thrombolysis catheter. The resultant slurry was passed through a filter with a pore size of 10 microns, and the radioactivity of the clot residue on the filter was measured. For each donor, the percentage of clot remaining was calculated from the residual radioactivity. RESULTS: The mean percentages of clot remaining were 72.0% for clots in saline (n = 10) and 44.4% for clots in rt-PA (n = 10) in donor 1 and 58.9% (n = 14) and 36.4% (n = 14), respectively, for donor 2. In both cases, the mean percentage of clot remaining was significantly lower when mechanical thrombolysis was performed in the presence of rt-PA. CONCLUSION: These results indicate the feasibility of combined pharmacologic and mechanical thrombolysis. PMID- 7873869 TI - Sinusoidal embolization: impact of iodized oil on hepatic microcirculation. AB - PURPOSE: To determine the effects of iodized oil, which is used in chemoembolization of liver cancer, on hepatic microcirculation and to measure the time required for recovery of microcirculation. MATERIALS AND METHODS: Iodized oil was injected in 0.1-, 0.2-, and 0.4-mL/kg doses into the hepatic artery in three groups of rats (n = 63). In vivo microscopy was performed during and immediately after the procedure and on days 1, 3, 7, 15, 30, and 60. A control group of rats underwent identical microscopy procedures. RESULTS: Changes in microcirculation occurred after injections with iodized oil. Oil injected into the hepatic artery entered the portal vein and flowed into the sinusoids to create an incomplete sinusoidal embolization. Recovery of the sinusoidal circulation occurred 3, 7, and 30 days after injections of 0.1, 0.2, and 0.4 mL/kg of oil, respectively. CONCLUSIONS: The liver tolerated oil embolization well. Despite the changes in microcirculation and a nonlinear recovery time, the microcirculation completely recovered, even with a 0.4-mL/kg dose. PMID- 7873870 TI - Persistent pneumothorax following embolization of a pulmonary arteriovenous malformation. PMID- 7873871 TI - Transcatheter embolization of traumatic mesenteric hemorrhage. PMID- 7873872 TI - Percutaneous transcholecystic approach to the rendezvous procedure when transhepatic access fails. AB - PURPOSE: Extrahepatic biliary obstruction can be managed endoscopically or percutaneously. When endoscopic therapy fails, percutaneous drainage with or without endoscopic assistance may be performed. However, transhepatic drainage may itself be unsuccessful. In such patients, a transcholecystic approach combined with endoscopic therapy was used to achieve biliary drainage. MATERIALS AND METHODS: After attempts at transhepatic biliary drainage failed, a percutaneous cholecystostomy was performed in four patients, with subsequent cannulation of the common bile duct, endoprosthesis insertion, or papillotomy. RESULTS: The success rate was 100%, with no major complication or procedure related mortality. Slight bleeding from a sphincterotomy was the only minor complication. CONCLUSION: When percutaneous transhepatic access to the bile duct fails, the transcholecystic route can be safely used with care to successfully achieve biliary drainage. PMID- 7873873 TI - Experimental nonsurgical female sterilization: transcervical implantation of microspindles in fallopian tubes. AB - PURPOSE: A nonsurgical method of female sterilization was investigated in rabbits. MATERIALS AND METHODS: A self-expanding microspindle (length 9-18 mm, diameter 1.5-2.0 mm) made from tubular metal mesh was implanted in a single fallopian tube of 12 rabbits via catheterization of a single uterus. The contralateral fallopian tube and uterus served as controls. Each rabbit was scheduled to undergo three cycles of breeding. Before delivery, absence of pregnancy on the side with the microspindle was verified with hysterography. RESULTS: Eight rabbits completed three cycles of breeding and pregnancy. Two rabbits had one pregnancy. Two rabbits did not conceive. Spindles were placed correctly in 11 rabbits. Successful contraception was achieved in nine rabbits, who had 25 gestations on the nonspindle side and no gestation on the spindle side. One rabbit, which received the shortest spindle, was bilaterally pregnant, indicating a failure of contraception on the spindle side. No spindles dislocated. Histologic study showed all spindles firmly embedded in the tubal wall without signs of inflammation. CONCLUSION: Microspindles of a certain minimum length have potential as a transcervically implantable, permanent intratubal contraceptive device. PMID- 7873874 TI - Fluoroscopically guided suprapubic cystostomy in complex urologic cases. AB - PURPOSE: To evaluate the efficacy of percutaneous suprapubic cystostomies performed by the interventional radiologist for complex urologic cases. MATERIALS AND METHODS: A retrospective analysis was done of the 25 cases referred to the radiology department for suprapubic cystostomies. The patients were referred because of unsuccessful placement or malposition of a suprapubic cystostomy tube. The procedure was performed with the Seldinger technique by using a 21-gauge needle for initial antegrade puncture and subsequent tract dilation and placement of 10-24-F catheters. RESULTS: In 24 of 25 cases (96%) the suprapubic cystostomy was successfully performed. After suprapubic cystostomy, eight patients (32%) underwent additional ancillary procedures by urologists through the suprapubic tract. The only major complication was perivesical fluid collection in one patient (4%), which was subsequently drained. Seventeen patients (68%) had transient hematuria. CONCLUSION: Percutaneous suprapubic cystostomy performed under fluoroscopic control is an effective and safe procedure ideally suited for the interventional radiologist, especially in complex urologic cases. PMID- 7873875 TI - The stumbler mutation maps to proximal mouse chromosome 2. AB - The cerebellar mouse mutation stumbler (stu) was mapped to proximal Chromosome (Chr) 2 with a recently developed polymerase chain reaction assay for endogenous retroviruses that vary between mouse strains. The stu locus resides between the markers D2Mit5 and D2Mit7. A number of developmentally or neurologically relevant candidate genes map in this region, including Bmi1, Dbh, Grin1, Notch1, Pax8, Rxra, and Spna2. Knowing the chromosomal localization of stu should simplify maintenance of the stumbler mouse stock and also enable analysis of the cerebellar defect in presymptomatic individuals. PMID- 7873876 TI - Deleted chromosome 20 from a patient with Alagille syndrome isolated in a cell hybrid through leucine transport selection: study of three candidate genes. AB - Alagille syndrome (AGS) is a well-defined genetic entity assigned to the short arm of Chromosome (Chr) 20 by a series of observations of AGS patients associated with microdeletions in this region. By fusing lymphoblastoid cells of an AGS patient that exhibited a microdeletion in the short arm of Chr 20 encompassing bands p11.23 to p12.3 with rodent thermosensitive mutant cells (CHOtsH1-1) deficient in-leucyl-tRNA synthetase, we isolated a somatic cell hybrid segregating the deleted human Chr 20. This hybrid clone, designated NR2, was characterized by several methods, including PCR, with eight pairs of oligonucleotides mapped to Chr 20: D20S5, D20S41, D20S42, D20S56, D20S57, D20S58, adenosine deaminase (ADA), and Prion protein (PRIP); Restriction Fragment Length Polymorphism (RFLP) analyses with four genomic anonymous probes (D20S5, cD3H12, D20S17, D20S18); and fluorescent in situ hybridization (FISH) with total human DNA and D20Z1, a sequence specific to the human Chr 20 centromere, as probes. The NR2 hybrid allowed us to exclude three candidate genes for AGS: hepatic nuclear factor 3 beta (HNF3 beta), paired box 1 (PAX1), and cystatin C (CST3) as shown by their localization outside of the deletion. The NR2 hybrid is a powerful tool for the mapping of new probes of this region, as well as for obtaining new informative probes specific for the deletion by subtractive cloning of the region. Such markers will be useful for linkage analysis and screening of cDNA libraries. PMID- 7873877 TI - Identification and genetic mapping of 151 dispersed members of 16 ribosomal protein multigene families in the mouse. AB - More than 150 individual members of 16 ribosomal protein multigene families were identified as DNA restriction fragments and genetically mapped. The ribosomal protein gene-related sequences are widely dispersed throughout the mouse genome. Map positions were determined by analysis of 144 progeny mice from both an interspecific (C57BL/6J x SPRET/Ei)F1 x SPRET/Ei and an intersubspecific (C57BL/6J x CAST/Ei)F1 x C57BL/6J backcross. In addition, 30 members of the multigene families encoding PGK1 ODC, and TPI, including five new loci for ODC and one new locus for TPI, were characterized and mapped. Interspecific backcross linkage data for 29 nonecotropic murine leukemia retroviruses endogenous to C57BL/6J mice are also reported. Transmission ratio distortions and recombination frequencies are compared between the two backcrosses. PMID- 7873878 TI - Intracisternal A-type particle elements as genetic markers: detection by repeat element viral element amplified locus-PCR. AB - We describe a novel, PCR-based technique termed REVEAL-PCR for examining the inheritance of intracisternal A-type particles (IAP). Amplifications use an unlabeled primer to SINE repeats and a radiolabeled primer to the IAP long terminal repeat; labeled products, which can be resolved on sequencing gels, are formed when IAPs lie in proximity to SINEs. With this technique we have identified a total of 124 polymorphisms in the BXH and CXS recombinant inbred strains. We suggest that this method will be equally applicable for examining other gene families present at around a thousand copies per genome. PMID- 7873879 TI - Of mice and Marfan: genetic linkage analyses of the fibrillin genes, Fbn1 and Fbn2, in the mouse genome. AB - The fibrillin genes, FBN1 and FBN2, encode large extracellular matrix glycoproteins involved in the structure and function of microfibrils. Mutations in FBN1 are found in patients with Marfan syndrome, a heritable connective tissue disease that primarily affects the cardiovascular, ocular, and skeletal systems. We extended the studies of these genes by determining their chromosomal position in the mouse genome. Restriction fragment length polymorphisms (RFLPs) between the progenitors of an interspecific backcross involving AEJ/Gn and Mus spretus mice were used to establish the segregation patterns of the murine homologs, Fbn1 and Fbn2, in the backcross progeny. The results position Fbn1 between the B2m and Illa genes on mouse Chromosome (Chr) 2 and establish its candidacy for the Tight skin (Tsk) mutation. The results position Fbn2 between the D18Mit35 and Pdgfrb loci in the central region of mouse Chr 18. Fbn2 maps near three mutations [bouncy (bc), plucked (pk), and shaker with syndactyly (sy)] and may be a candidate for the pk mutation. PMID- 7873880 TI - Cloning of a mouse protein kinase A catalytic subunit pseudogene and chromosomal mapping of C subunit isoforms. AB - Two isoforms of the protein kinase A catalytic subunit, C alpha and C beta, have previously been described in the mouse. We now report the cloning and characterization of a novel C-related sequence, Cx, from a murine genomic library. Cx is 89.8% identical to part of the C alpha coding region, but lacks all of the introns present in this gene, suggesting that it arose via retroposition. The existence of several frameshift mutations, premature termination codons, and missense mutations at critical sites confirms that it is a pseudogene. Furthermore, we are unable to detect any expression. Homology with functional protein kinase genes commences exactly at the first intron splice junction in C alpha, downstream of the expected translational start codon. Cx is also truncated at its 3' end by the interposition of two distinct, contiguous LINE-1 elements. By fluorescence in situ hybridization, we demonstrate that Cx is located on the X Chromosome (Chr), at band F3. This is displaced from its functional homologs, C alpha and C beta, which we map to mouse Chrs 8 (band C3) and 3 (band H3), respectively. PMID- 7873881 TI - Characterization of microsatellites from flow-sorted porcine chromosome 13. AB - Porcine flow-sorted Chromosome (Chr) 13 was PCR amplified with primers based on porcine short interspersed element (SINE) sequences. The product was cloned, gridded in microtiter plates, and screened with a [GT]10 oligonucleotide which gave 45 positive clones. Sequencing of these clones showed that 36 were unique, and 26 [GT]n microsatellites were characterized. Six other simple repeat sequences, the majority of which were associated with the 3' end of the SINE sequence, were also detected. Twenty-one primers sets were selected, and 13 of these detected useful polymorphisms in the grandparents (n = 26) of the European porcine mapping collaboration (PiGMaP) reference families. These 13 markers were mapped in the "PiGMaP" reference families, and a two-point linkage analysis was performed. The Lod scores indicated that three of the markers were not linked and the remaining 11 formed two linkage groups of two and nine markers respectively. The larger linkage group was also linked to the transferrin locus, permitting assignment of nine markers to porcine Chr 13. PMID- 7873882 TI - Chromosomal assignment of 11 loci in the rat by mouse-rat somatic hybrids and linkage. AB - Eleven rat genes have been assigned to rat chromosomes by use of mouse x rat somatic hybrids and/or use of linkage to known chromosome markers. Among them, the genes for the inducible nitric oxide synthase (Nos2) and for a vasoactive intestinal peptide receptor (Vipr) are potential candidates for genetic regulation of blood pressure and were localized to rat Chromosomes (Chrs) 10 and 8 respectively. Genes for gastric H,K-ATPase alpha subunit (Atp4a), Class I alcohol dehydrogenase (Adh), and aldolase C (Aldoc) were localized to Chrs 1, 2, and 10 respectively, and thus provide more DNA markers for genetic mapping of quantitative trait loci for blood pressure on those chromosomes. Genes for alkaline phosphatase (Alp1) and cardiac AE-3 Cl-/HCO3- exchanger (Ae3) were both localized to Chr 9. Genes for glutamate dehydrogenase (Glud) and gastric H,K ATPase beta subunit (Atp4b) were localized to Chr 16. The ornithine decarboxylase (Odc) gene and ornithine decarboxylase pseudogene (Odcp) were localized to Chrs 6 and 11 respectively. PMID- 7873883 TI - Sequence evolution of SRY gene within Bovidae family. PMID- 7873884 TI - Allelic variation of the type 2 tumor necrosis factor receptor gene. PMID- 7873885 TI - The cDNA sequence of mouse uroporphyrinogen III synthase and assignment to mouse chromosome 7. PMID- 7873886 TI - Close genetic linkage between DRBP1 and CYP21 in the MHC of cattle. PMID- 7873887 TI - Transfer of brain dopamine system-specific quantitative trait loci onto a C57BL/6ByJ background. PMID- 7873888 TI - Localization of the peptidylglycine alpha-amidating monooxygenase gene (Pam) introduces a region of homology between human chromosome 5q and mouse chromosome 1. PMID- 7873889 TI - An MMTV integration site on the centromere proximal region of mouse chromosome 11. PMID- 7873890 TI - Genetic linkage of the erythroid-specific delta-aminolevulinate synthase gene (Alas2) to the distal region of the mouse X chromosome. PMID- 7873891 TI - Assignment of the transition protein 1 (TNP1) gene to U17 bovine synteny group by PCR. PMID- 7873892 TI - Localization of a novel, LPS-inducible member of the thymidylate kinase family to mouse chromosome 12. PMID- 7873893 TI - School nursing: trends for the future. PMID- 7873894 TI - Identifying potential dropouts through school health records. AB - This study of the records of 255 ninth grade, inner-city Midwestern high school students shows that students who drop out of school are several times as likely to have incomplete health information in the school health record as students who stay in school. A cluster of five variables--vision screening, scoliosis screening, visits to the health office, age and attendance--were found to provide 85% or better accuracy in estimating actual drop-out rates. Missing or incomplete data in combination with attendance data thus become powerful predictors of potential dropouts. PMID- 7873895 TI - Promoting informed decision-making about tattooing for adolescents. AB - In the February issue, the authors identified tattooing as an adolescent at-risk behavior, summarizing adverse purchase and possession factors as well as potential health threats of blood-borne disease. This information stems from a study of adolescents in five suburban high schools and one large urban school district in Texas. Promoting self-identity seems to be the key motivation for the tattooing. Investigating specific risk-taking behaviors of adolescents is important in order to create applicable health-promotion strategies. This article summarizes the development of a health education brochure, which was created on the basis of a review of the literature, an analysis of data, and field testing of the product. The purpose of the health information is to emphasize potential risks, pose definite questions and actions to minimize the risks, and encourage reconsideration or postponement of tattoo decisions. PMID- 7873896 TI - School health delivery programs throughout the United States. AB - This is the second of a two-part series on School-based and School-linked Health Centers. Through NASN's Board of Directors, various models of health service delivery were examined, and leaders in school nursing interviewed from five different sites. The first article, which appeared in the February 1994 issue of the Journal of School Nursing, addressed the purpose of integrating traditional school health services with newer models of health service delivery, depicted possible models and considered some of the issues of this union. PMID- 7873897 TI - Nursing practice management. PMID- 7873898 TI - Help! Where to find it. PMID- 7873899 TI - EPSDT model training program. AB - The National Association of School Nurses plans to present an Early Periodic Screening, Diagnosis and Treatment (EPSDT) model training program for school nurses at the NASN Annual Conference in Orlando, Florida on June 29, 1994. This program is designed to provide school nurses with essential information concerning the development and implementation of the EPSDT program for Medicaid eligible students in their schools. It capitalizes on the central role of school nurses as the primary health professionals, health care initiators and health care coordinators of EPSDT program implementation. PMID- 7873900 TI - Planning for success: the first steps in new program development. AB - New program development can be an exciting endeavor when the outcomes are successful. The opportunities for success are increased when an initial four-step planning process is emphasized prior to implementing specific programmatic efforts. This four-step process is called the "pre-start up plan." Included are: mission statement clarification, a stakeholder analysis, problem identification, and a strengths, weaknesses, opportunities, and threats (SWOT) analysis. None of this is difficult to accomplish, and it provides important input to the design of a successful new program. PMID- 7873901 TI - Case management for children with attention deficit hyperactivity disorder. PMID- 7873902 TI - The changing role of school nurses--one state's experience. AB - The purpose of this study was to identify the scope of management responsibilities, health education, and early education for handicapped children, as well as clinical and program dimensions of the school nurse role. Changes in responsibilities over the last five years were explored in one state by utilizing a questionnaire aimed at providing a profile of the school nurse's perceived behavioral patterns. In every dimension of the school nurse role included in this study, the responsibilities of the school nurse had either increased or stayed the same on an overall basis. PMID- 7873903 TI - Children from alcoholic families--a population at risk. AB - This article focuses on children of alcoholics as a population at risk, and discusses strategies for assessment and intervention by school nurses. Information about alcohol abuse and the effects of problem drinking on children is provided. Case history examples will offer additional illustration, with resiliency being highlighted. PMID- 7873904 TI - Case management in the school setting. PMID- 7873905 TI - Electronic communication. AB - This article is Part 1 of a three-part series on electronic communication for school nurses. In this issue, we will discuss the definition of electronic communication and the hardware and software needed to access electronic resources. PMID- 7873906 TI - The at-risk student: a study of visits to the school nurse. AB - This study compared rural public school students defined as at-risk and those who were defined as not at-risk to determine if there was a significant difference in the proportion of each group who visited the school nurse. Significant differences were observed between the at-risk and not at-risk students. Implications of these results for the school nurse are discussed. PMID- 7873907 TI - School nursing in the 21st century: prediction and readiness. AB - The complex health and education needs of today's students are prompting schools to develop more responsive school health programs. School nurses' preparation for roles in these emerging programs requires both a vision of future practice and a clear recognition of present skill levels. This study compared the vision of practice in the twenty-first century held by school nurses in a rural, mid-plains state with the vision of a national expert school nurse panel. The findings have implications for role evolution and educational preparation. PMID- 7873908 TI - Prevalence of adolescent health risk behaviors: school health implications. AB - This state survey randomly selected 2,037 ninth- and twelfth-grade students to determine the onset and prevalence of health risk behaviors. A higher pattern of risk-taking behavior was found among younger in comparison with older students. Gender differences were also noted. Implications for school health intervention are discussed. PMID- 7873910 TI - DNR orders in schools--revisited. PMID- 7873909 TI - Using genograms and ecomaps in schools. AB - Genograms and ecomaps are visual tools for assessing and planning care for children and adolescents. Using a simple format of the family tree, school nurses can enhance nursing care by viewing students in the context of their history and the connections that are part of their everyday life. Genograms and ecomaps can be used to clarify information and organize it in a brief, but relatively comprehensive, format. A case study illustrates the application of these techniques in the school setting. PMID- 7873911 TI - Electronic communication. Part II. AB - This article is Part 2 of a three-part series on electronic communication for school nurses. The October 1994 column provided an introduction to electronic communication, the linking of computers to exchange information. The hardware and software required for this medium were described. This column will examine the primary uses of electronic communication: e-mail, bulletin boards, databases, and file transfers. PMID- 7873912 TI - Nursing research in a school setting. AB - As more nurses are expanding their role and moving beyond traditional staff nursing, it is becoming increasingly common to find nurses conducting research. The utilization of schools as research sites is on the rise. Life events in families, such as divorce, unemployment, and geographic relocation, predispose school-aged children to high levels of stress, and nurse researchers are in a position to examine students' responses to these stressors. The purpose of this article is to discuss four issues inherent to research in schools, and to share some strategies which were effective. The issues include recruitment of subjects, informed consent, interviewing subjects, and coping with the unpredictable. PMID- 7873913 TI - [Safety from HIV infection of preserved blood from Germany]. PMID- 7873914 TI - [A retrospective study of the practice of "look-back" procedures, on the incidence of HIV-1/2-positive blood donors and the risk of transfusion-associated HIV infection in public-community blood banks in Germany]. AB - OBJECTIVE: 'Look-back' investigations can reveal and confirm transfusion transmitted infectious diseases and provide data for risk calculations of blood transfusions. DESIGN: In 1993 we distributed a questionnaire to all governmental and communal blood transfusion services in Germany. The questionnaire comprised questions about the methods, numbers and results of look-back investigations in case of HIV-1/2-positive blood donors with previous donations and in case of HIV 1/2-positive recipients of blood transfusions. The questionnaire was returned by almost all blood transfusion services (n = 75). One additional institution briefly informed us by telephone. SETTING: All governmental and communal blood transfusion services in Germany. PATIENTS: All recipients of blood or blood products in the years from 1985 till the end of 1992 who were treated in hospitals supplied by the transfusion services defined above. INTERVENTIONS: None. RESULTS: All blood transfusion services included have performed look-back studies since 1985. The methods used varied considerably. The interval of looking back mostly was sufficient. A main problem was the poor documentation in the medical records. The incidence of HIV-1/2-positive blood donations decreased from 11.6/100,000 in 1985 to 3.4/100,000 in 1992. Only 7 of 73 transfusion-transmitted HIV infections derived from transfusions after the introduction of HIV testing (October 1985). Since then the risk of transfusion-transmitted HIV infection can be calculated as 1/800,000 whole-blood donations of governmental and communal blood transfusion services. CONCLUSIONS: Since the introduction of HIV testing the risk of transfusion-transmitted HIV infection in Germany has been very low, at a rather stable rate of 1/800,000. The data from the look-back studies confirm the previous estimations of the risk of transfusion-transmitted HIV infections, which was calculated by the HIV incidence in the donor population. Nevertheless there is a need for standardization of look-back investigations. PMID- 7873915 TI - [HIV retrospective study of the German Red Cross blood donation service in Germany]. AB - OBJECTIVE: It was tried to retrospectively identify HIV infections in recipients of transfusions from donors who were tested HIV positive at a subsequent donation. These lookback data were traced back to answer the following questions: 1. How many transfusion recipients were infected before the start of the routine HIV testing in 1985? 2. How great is the risk of HIV infections from infected but not yet HIV antibody-positive donors? 3. Furthermore, the transfusion of HIV infected transfusion recipients was traced back to the involved donor to establish causality. DESIGN: Retrospective ('lookback') study. SETTING: HIV Study Group of the Red Cross Blood Banks of the Federal Republic of Germany. PARTICIPANTS: Preceding donations of HIV antibody-positive repeat donors were traced back to the transfusion recipients in order to establish their HIV antibody status. In a second lookback study, HIV-infected transfusion recipients and their corresponding donors were investigated after they had been reported to the blood bank as infected by transfusion-associated HIV. INTERVENTIONS: None. RESULTS: Recipients of 156 respectively 133 transfusions from repeat donors found to be Western blot-positive were investigated from 1985 to 1987 and from 1987 to 1992, respectively. About 50% of the recipients had died. About 40% of the recipients could not be examined, because they either were not available for testing or refused to be tested or because it was impossible to clarify the fate of the blood products. 25 HIV recipients were identified from 1981 to 1985, when routine HIV testing began. Nine transfusion-associated HIV infections were identified from 1985 to 1992. 25 million units of blood were prepared during this period. CONCLUSIONS: The risk of HIV transmission by tested transfusions is extremely rare (in the order of 1:1 million). The second lookback study suggests that in more than 50% of the blood recipients in whom HIV infection was attributed to transfusion, a causal relationship to an infected donor could not be established. PMID- 7873916 TI - Blood transfusion in late anemia of prematurity: effect on oxygen consumption, heart rate, and weight gain in otherwise healthy infants. AB - BACKGROUND: In premature infants there is no universally accepted definition of anemia requiring transfusion. We designed the present investigation to study the effects of red blood cell transfusion (based on simple transfusion rules) on weight gain, energy metabolism, and heart rate in otherwise healthy preterm infants. PATIENTS AND METHODS: We measured oxygen consumption (VO2), respiratory quotient (RQ) and energy expenditure (EE) by 4-hour indirect calorimetry, and assessed weight gain over 7 days and heart rate in 12 infants with late anemia of prematurity before and after red blood cell transfusion (10 ml/kg). At the time of transfusion, postmenstrual age was 38 +/- 1 weeks (mean +/- SEM), body weight 2.14 +/- 0.13 kg, and hemoglobin concentration 7.7 +/- 0.3 g/dl (range: 5.5-9.2). RESULTS: Red blood cell transfusion increased the hemoglobin concentration by 3.8 +/- 0.5 g/dl, but had no significant effect on weight gain (15.4 +/- 2.4 vs. 13.8 +/- 1.8 g/kg/day), VO2 (8.7 +/- 0.3 vs. 8.7 +/- 0.3 ml/kg/min), minimal VO2 (7.2 +/- 0.3 vs. 7.7 +/- 0.4 ml/kg/min), RQ (0.96 +/- 0.02 vs. 0.95 +/- 0.02), EE (50 +/- 2 vs. 51 +/- 2 kcal/kg/day), and heart rate (160 +/- 3 vs. 158 +/- 3 min-1). CONCLUSION: We conclude that oxygen supply and energy metabolism were not compromised in the anemic preterm infants at the time of red blood cell transfusion. PMID- 7873918 TI - HLA-DPB1 typing by PCR-SSO reverse dot blot hybridization after group-specific amplification. AB - BACKGROUND: The allelic diversity of HLA-DPB1 antigens can be determined at the DNA level after PCR amplification. The pattern of polymorphism at the DPB1 locus makes it difficult to unambiguously assign all genotypes in a typing system using one single pair of generic primers. MATERIALS AND METHODS: We apply here a simple technique based on the reverse dot blot analysis to the typing of HLA-DPB1 alleles. In order to increase its resolution, a group-specific amplification based on sequence variations of the polymorphic region F was used subdividing the HLA-DPB1 alleles in 2 nonoverlapping families. A separate analysis was then performed within each group of alleles. RESULTS: Using these 2 primer pairs, 21 group 1 and 30 group 2 alleles were separately amplified. From 1,378 possible allele combinations for DPB1*0101-5301 only 33 gave ambiguous typing results compared to 61 using a single pair of generic primers. CONCLUSIONS: This procedure provides a rapid and simple HLA-DPB1 genotyping. Especially in heterozygotes the hybridization patterns were easier to interpret. The utilization of group-specific amplification substantially reduced ambiguous typing results. PMID- 7873917 TI - Chemically defined structured lipids with omega-3 fatty acids maintain splanchnic blood flow in a low-dose continuous endotoxin model. AB - BACKGROUND: Disturbances of microcirculation and accompanying alterations of oxygen supply are central pathophysiological events in trauma and sepsis. There is evidence that omega-3 fatty acids can modulate prostaglandin formation and thereby regional blood flow. The aim of the study was to determine the effects of chemically defined structured lipids (SL) with omega-3 fatty acids in position sn 2 (MFM) compared to SL with omega-6 fatty acids in position sn-2 (MLM) on cardiac output (CO) and splanchnic blood flow in a low-dose endotoxin (E, 1 mg.kgBW-1.day 1) rat model. MATERIALS AND METHODS: 24 male Sprague Dawley rats, divided in 4 groups (n = 6; MLM, MLM+E, MFM, MFM+E) received for 48 h a total parenteral nutrition. CO and regional blood flow were measured with 85strontium-labelled microspheres (16.5 +/- 0.1 microns). RESULTS: There was a slight rise in CO in the E groups compared to the control groups. Application of E resulted in a marked decrease of intestinal perfusion in the MLM-fed animals, whereas the MFM fed animals showed only a minimal reduction. This decrease of portal blood flow to the liver was accompanied by an elevation of arterial blood flow to the liver. This compensatory increase in arterial liver blood flow was more pronounced in the MFM-fed animals, resulting in a total liver blood flow which was not different from the control group. CONCLUSIONS: The results of this study implicate that 48 h of intravenous feeding with chemically defined SL with an omega-3 fatty acid in position sn-2 can significantly influence splanchnic bed perfusion in a low-dose endotoxin rat model. The better splanchnic perfusion may be mediated by a shift in prostaglandin production. PMID- 7873919 TI - Activation of complement by cold agglutinins. AB - OBJECTIVE: To review recent reports on the interaction of cold agglutinins with the complement system and its relevance to cold agglutinin disease. DATA SOURCES: Review articles and original papers have been selected for this contribution. SELECTION CRITERIA: The report focuses on experimental data available from in vitro studies as well as clinical findings regarding the mechanisms of cold agglutinin-induced complement activation. RESULTS: Despite the observation that only few cold agglutinins (almost exclusively IgM molecules with anti-I specificity) induce in vitro hemolysis of human red blood cells with human serum (homologous system), the vast majority of these autoantibodies are able to initiate the classical pathway sequence with the fixation of C1 and to a lesser degree of C4. The ability of IgM cold agglutinins to activate, in principle, complement is demonstrated by their hemolytic efficiency in the presence of animal serum as a source of heterologous complement. In addition to the thermal amplitude of cold agglutinin binding, a possible interference with membrane regulatory proteins may render certain cold agglutinins hemolytically active in a homologous system. CONCLUSION: Despite a hemolytic inefficiency, cold agglutinin induced fixation of early complement components up to C3 leads to an accelerated clearance of red cells from the circulation by hepatic sequestration. However, it is not yet clear, to what degree these cells are eliminated by the reticuloendothelial system or whether they return to the circulation. Dependent on the amount of membrane-bound C3 fragments these cells may even be protected against further cold agglutinin-induced complement attack. PMID- 7873920 TI - Red cell destruction in cold agglutinin disease. AB - OBJECTIVE: The severity of autoimmune hemolytic anemia (AIHA) caused by cold agglutinins (CAs) is known to differ markedly in chronic CA disease as well as in postinfection cold agglutination. The various cold agglutinin specificities and mechanisms of red cell destruction are described. DATA SOURCES: Original papers and reviews of the German and English literature (Medline research); own results. SELECTION CRITERIA: Original papers and reviews of the recent years on studies of the biochemistry and specificity of CAs and the pathophysiology of AIHA. RESULTS: A crucial point for the severity of AIHA caused by CAs is the CA-binding capacity to red cells in vivo. This is reflected by the serologic behavior of the actual CA in vitro, represented by its thermal amplitude. Because most CAs are IgM molecules, red cell destruction by CAs is limited to mechanisms initiated by complement (C) activation. In recent years, several CA specificities, in addition to anti-I/i, have been identified on a serological and biochemical basis. CAs of the IgG and rarely of the IgA isotypes have been found. CONCLUSION: The CA induced red cell destruction does not only depend on CA titer or its thermal amplitude. The severity of CA-induced AIHA may also depend on CA isotype and/or specificity. Therefore, the complement activation capacity of CAs with a given isotype but different specificities has to be elucidated in further studies. PMID- 7873921 TI - Ricin B chain fragments expressed in Escherichia coli are able to bind free galactose in contrast to the full length polypeptide. AB - Deleted forms of ricin B chain (RTB) containing only one of the two galactose binding sites were produced in E. coli and targeted to the periplasm by fusion to the ompA or ompF signal sequences. The proteins were then isolated from the periplasm and their sugar binding properties assessed. Previous studies investigating the properties of such proteins produced in Xenopus laevis oocytes suggested that deleted forms of RTB, when not glycosylated, retain their ability to bind simple sugars, unlike the full-length unglycosylated proteins. When produced in E. coli however we found that only one, EB733, of a number of deleted forms of RTB closely related to those previously produced in Xenopus laevis oocytes, bound to simple sugars. All of the deletion forms of RTB were found to bind in the asialofetuin binding assay; an assay which has been previously utilized to measure binding of lectins to the terminal galactose residues of glycoprotein oligosaccharides. However, in contrast to glycosylated RTB, binding of the deletion mutants could be competed to only a small degree or not at all with galactose. The only deletion mutant observed to bind to free galactose when produced in E. coli corresponded closely to the complete domain 2 of RTB. It is assumed that this mutant forms a stable structure similar to that of the C terminal domain in the full-length protein. The structural integrity of EB733 was not only suggested by its sugar binding properties and solubility but also by its consistently higher level of expression and the absence of any apparent susceptibility to E. coli proteases. PMID- 7873922 TI - Purification of lectins from the stems of peanut plants. AB - The stem of the peanut plant contains two lectins, a methyl alpha-mannoside specific lectin (SL-I) and a lactose/cellobiose specific lectin (SL-II). These lectins are found to be developmentally regulated and maximum activities are observed in 3-4-weeks-old plants. The two lectins SL-I and SL-II have been purified from 3-week-old stem by affinity chromatography on Sephadex G-50 and guar gum matrices respectively. Both are glycosylated lectins and have the identical subunit molecular weight of 31 kDa. PMID- 7873923 TI - Changes in S-type lectin localization in neuroblastoma cells (N1E115) upon differentiation. AB - The distribution of a 14.4 kDa S-type lectin was examined in murine neuroblastoma cells, either undifferentiated or after differentiation induced by dibutyryl cyclic adenosine monophosphate. In undifferentiated cells the immunoreactivity was detected extracellularly, associated with the plasma membrane and in bulges released into the extracellular milieu. Important modifications of the lectin localization were associated with the differentiation process that induced an increased cytosolic expression and a decreased externalization. Possible functions for the lectin expressed intracellularly in the differentiated cells are also considered. PMID- 7873924 TI - Binding of the galactose-specific Pseudomonas aeruginosa lectin, PA-I, to glycosphingolipids and other glycoconjugates. AB - The carbohydrate-binding specificity of Pseudomonas aeruginosa lectin I (PA-I) in iodinated or biotinylated form was studied. A large number of glycosphingolipids, as well as some glycoproteins and neoglycoproteins were used as ligands. Also, inhibition by free saccharides of PA-I binding to glycosphingolipids was tested. It was found that the lectin binds most strongly to terminal and nonsubstituted Gal alpha 3Gal- or Gal alpha 4Gal-structures. PMID- 7873925 TI - Characterization of isolectins in Tetracarpidium conophorum seeds (Nigerian walnut). AB - A lectin preparation obtained from Tetracarpidium conophorum (Nigerian walnut) by affinity chromatography of seed extracts on lactose-agarose has been shown to contain two components by gel filtration on Sephadex G150. The larger component Tetracarpidium conophorum agglutinin I (TCAI) is a disulphide-bonded 70 kDa homodimer whereas the second component TCAII is a 34 kDa monomeric protein. Amino terminal aminoacid sequencing shows identity in TCAI and TCAII for the first fifteen residues after which the sequences diverge. The N-terminal sequences of TCAI and TCAII show identity with sequences in the B-chains of ricin and Ricinus communis agglutinin I (RCAI) in eleven of the initial fifteen residues. Thereafter TCAI appears to be homologous to the ricin B chain whereas TCAII is more homologous with the B chain of RCAI. A limited screening of the carbohydrate binding specificity of TCAII by affinity chromatography of defined oligosaccharides on TCAII Sepharose columns shows that the binding specificity reported earlier for affinity purified Tetracarpidium conophorum isolectins (Sato S, Animashaun T, Hughes RC (1991) J Biol Chem 266:11485-94) reflects the binding properties of TCAII which is the major isolectin in unfractionated lectin preparations. PMID- 7873926 TI - Complement-dependent cytotoxic activity of serum mannan-binding protein towards mammalian cells with surface-exposed high-mannose type glycans. AB - Serum mannan-binding protein (S-MBP), a lectin specific for mannose and N acetylglucosamine, activates complement through the classical pathway. With the help of complement, S-MBP lyses red blood cells which have been coated with yeast mannan and kills bacteria which have N-acetylglucosamine and/or L-glycero-D-manno heptose on their core oligosaccharide. In this study, we examined whether mammalian cells, on which S-MBP could bound, are killed by a complement-dependent mechanism. When baby hamster kidney (BHK) cells were treated with an alpha mannosidase inhibitor, 1-deoxymannojirimycin (dMM), most of the cellular oligosaccharides were transformed from the complex-type to the high mannose-type. S-MBP bound to the dMM-treated BHK cells in the presence of Ca2+, and this binding was eliminated by mannose. When dMM-treated cells, labelled with 51Cr, were incubated with complement, radioactivity was released in a dose-dependent manner by S-MBP and complement. This release was not observed with heat inactivated complement. These observations suggest that S-MBP is able, with the help of complement, to kill not only exogenous microorganisms but also mammalian cells which have high mannose-type oligosaccharides exposed on their surfaces. PMID- 7873927 TI - Comparative study of the post-translational processing of the mannose-binding lectins in the bulbs of garlic (Allium sativum L.) and ramsons (Allium ursinum L.). AB - The biosynthesis and processing of the homodimeric and heterodimeric lectins from the bulbs of garlic (Allium sativum) and ramsons (wild garlic; Allium ursinum) were studied using pulse and pulse-chase labelling experiments on developing bulbs. By combining the results of the in vivo biosynthesis studies and the cDNA cloning of the respective lectins, the sequence of events leading from the primary translation products into the mature lectin polypeptides could be reconstructed. From this it is demonstrated that garlic and ramsons use different schemes of post-translational modifications in order to synthesize apparently similar lectins from totally different precursors. Both the homomeric garlic lectin (ASAII) and its homologue in ramsons (AUAII) are synthesized on the endoplasmic reticulum (ER) as nonglycosylated 13.5 kDa precursors, which, after their transport out of the ER are converted into the mature 12.0 kDa lectin polypeptides by the cleavage of a C-terminal peptide. The heterodimeric garlic lectin ASAI is synthesized on the ER as a single glycosylated precursor of 38 kDa, which after its transport out of the ER undergoes a complex processing which gives rise to two mature lectin subunits of 11.5 and 12.5 kDa. In contrast, both subunits of the heterodimeric ramsons lectin AUAI are synthesized separately on the ER as glycosylated precursors, which after their transport out of the ER are deglycosylated and further processed into the mature lectin polypeptides by the cleavage of a C-terminal peptide. PMID- 7873928 TI - The monomeric and dimeric mannose-binding proteins from the Orchidaceae species Listera ovata and Epipactis helleborine: sequence homologies and differences in biological activities. AB - The Orchidaceae species Listera ovata and Epipactis helleborine contain two types of mannose-binding proteins. Using a combination of affinity chromatography on mannose-Sepharose-4B and ion exchange chromatography on a Mono-S column eight different mannose-binding proteins were isolated from the leaves of Listera ovata. Whereas seven of these mannose-binding proteins have agglutination activity and occur as dimers composed of lectin subunits of 11-13 kDa, the eighth mannose-binding protein is a monomer of 14 kDa devoid of agglutination activity. Moreover, the monomeric mannose-binding protein does not react with an antiserum raised against the dimeric lectin and, in contrast to the lectins, is completely inactive when tested for antiretroviral activity against human immunodeficiency virus type 1 and type 2. Mannose-binding proteins with similar properties were also found in the leaves of Epipactis helleborine. However, in contrast to Listera only one lectin was found in Epipactis. Despite the obvious differences in molecular structure and biological activities molecular cloning of different mannose-binding proteins from Listera and Epipactis has shown that these proteins are related and some parts of the sequences show a high degree of sequence homology indicating that they have been conserved through evolution. PMID- 7873929 TI - Characterization and cellular localization by monoclonal antibodies of the 60 kDa mannose specific lectin of human promyelocytic cells, HL60. AB - Myelomonocytic lineage cells express an M(r) 60,000 mannose specific lectin, MR60 (Pimpaneau et al. (1991), Carbohydr Res 213: 95-108). Under non-reducing conditions, this protein migrates as a 120,000 protein. MR60 does not contain any N-glycan moiety cleavable by the action of N-glycanase. MR60 induces a sugar selective aggregation of beads coated with glycosylated albumin: beads bearing alpha-D-mannosyl residues are aggregated while beads bearing alpha-D-glucosyl residues are not. A monoclonal antibody Lec101B, specific for MR60, recognizes a single M(r) 60,000 protein by Western blotting. This monoclonal antibody does not label the cell surface of cells expressing MR60, but decorates intracellular vesicles upon permeabilization of these cells. PMID- 7873930 TI - Cell type-dependent alterations of binding of synthetic blood group antigen related oligosaccharides in lung cancer. AB - Blood group antigen-related oligosaccharides have been implicated in growth regulation, cell mobility control and adhesion; we are therefore interested in the localization of receptors for these oligosaccharides in tumour cells. Labelled neoglycoconjugates that carry synthetic sugar structures are suitable tools to determine: whether such binding sites are present in human lung cancer; whether structural alterations of the glycoligand part will affect extent of binding; and whether cell type-associated alterations can be detected. Sections from 121 cases of lung cancer, representing small cell and non-small cell lung carcinoma, mesothelioma and metastases from extrapulmonary primary carcinomas were used to study the binding of nine synthetic AH- and Le-related oligosaccharides. Probes with fucose-alpha 1-3/4-N-acetylglucosamine-beta 1-R, an A-like disaccharide and 3'-sulfated galactose as ligand appear to bind less well to small cell than to non-small cell lung cancer cases, whereas Lec-disaccharide distinguishes mesothelioma from metastatic carcinoma. The latter ligand, A-like disaccharide and H (type III)-like trisaccharide exhibit evident cell type associated differences in extent of binding. Thus, tailor-made neoglycoconjugates constitute a promising class of histopathological tools that warrants further study. PMID- 7873931 TI - Galectin-3: differential accumulation of distinct mRNAs in serum-stimulated mouse 3T3 fibroblasts. AB - The murine Galectin-3 gene spans approximately 12 kb of DNA and contains six exons, with the translation initiation codon located in exon II. On the basis of restriction mapping and sequence analysis of the DNA upstream of exon II, primer extension assays, rapid amplification of cDNA ends, and ribonuclease protection assays were designed and carried out to determine the initiation site of transcription and the sequence of exon I. The results revealed at least two transcription initiation sites (alpha and delta), each of which appears to be specifically associated with the use of alternative donor splice sites, resulting in distinct mRNA species. Type I message initiates at transcription start site delta, uses splice donor site No. 2, retaining a 27 bp sequence, whereas type II message initiates at transcription start site alpha, uses splice donor site No. 1, resulting in the loss of the 27 bp sequence. Primer extension assays carried out with mRNA isolated from 3T3 fibroblasts at various times after serum stimulation indicate that while the type II message varies in level only a little over the first 20 h, there is dramatic accumulation of the type I message, which peaks at 16 h post mitogen addition. PMID- 7873932 TI - Carbohydrate binding activities of Bradyrhizobium japonicum: IV. Effect of lactose and flavones on the expression of the lectin, BJ38. AB - BJ38 is a galactose/lactose-specific lectin (M(r) approximately 38,000) found at one pole of Bradyrhizobium japonicum. It has been implicated in mediating the adhesion of the bacteria to soybean roots, leading to the establishment of a nitrogen-fixing symbiosis. When the ligand lactose is added to cultures of the bacteria for at least 1 h prior to harvesting the cells for BJ38 isolation, the yield of the protein was found to be elevated in a dose-dependent fashion. Half maximal stimulation was observed at approximately 50 microM; the effect was saturated at approximately 1 mM, where a 10-fold higher yield of BJ38 was obtained. Saccharides with a lower affinity for BJ38 than lactose yielded a correspondingly smaller induction effect when compared at a concentration of 1 mM. The higher level of BJ38 induced by lactose is also manifested by an elevated amount of BJ38 detectable at the cell surface and by a higher number of B. japonicum cells adsorbed onto soybean cells. Surprisingly, the induction of BJ38 expression seen with lactose was also observed with certain, but not all, flavonoids that induce the nod genes of the bacteria; genistein mimicked the induction observed with lactose, whereas luteolin failed to stimulate BJ38 production. PMID- 7873933 TI - Vicia villosa B4 lectin is the second anti-Tn lectin shown to react better with blood group N than M antigen. AB - Earlier studies showed that Moluccella laevis lectin, which has anti-Tn specificity, reacts more strongly with native or desialylated blood group N glycophorin A than with the respective glycophorins of blood group M. We now present results indicating that Vicia villosa B4 anti-Tn lectin, which does not show detectable reaction with untreated glycophorins or erythrocytes, reacts better with desialylated blood group N antigen than with asialo M antigen. This was demonstrated by three assays: (1) agglutination of asialoerythrocytes; (2) binding of biotinylated lectin to asialoerythrocytes immobilized on ELISA plates; and (3) inhibition of lectin binding to asialo-agalactoglycophorin with asialoglycophorins M and N. These results supply further support for the conclusion that glycophorin of blood group N has more GalNAc residues unsubstituted with Gal (Tn receptors) than glycophorin of blood group M. PMID- 7873934 TI - Mutational analysis of the sugar-binding site of pea lectin. AB - Comparison of x-ray crystal structures of several legume lectins, co-crystallized with sugar molecules, showed a strong conservation of amino acid residues directly involved in ligand binding. For pea (Pisum sativum) lectin (PSL), these conserved amino acids can be classified into three groups: (I) D81 and N125, present in all legume lectins studied so far; (II) G99 and G216, conserved in almost all legume lectins; and (III) A217 and E218, which are only found in Vicieae lectins and are possibly determinants of sugar-binding specificity. Each of these amino acids in PSL was changed by site-directed mutagenesis, resulting in PSL molecules with single substitutions: for group I D81A, D81N, N125A; for group II G99R, G216L; and for group III A217L, E218Q, respectively. PSL double mutant Y124R; A126S was included as a control. The modified PSL molecules appeared not to be affected in their ability to form dimeric proteins, whereas the sugar-binding activity of each of the PSL mutants, with the exception of the control mutant (as shown by haemagglutination assays), was completely eliminated. These results confirm the model of the sugar-binding site of Vicieae lectins as deduced from X-ray analysis. PMID- 7873935 TI - Tumour markers and primary site of cancer. PMID- 7873936 TI - Management of breast cancer. PMID- 7873937 TI - Early origin of coronary heart disease (the "Barker hypothesis") PMID- 7873938 TI - Clinical audit in primary health care: towards quality assurance. PMID- 7873939 TI - Injuries to child pedestrians. PMID- 7873940 TI - Hepatitis E. PMID- 7873941 TI - Profiting from the NHS. PMID- 7873942 TI - Countries struggle with hepatitis C contamination. PMID- 7873943 TI - Orthopaedic consultants warn of future shortages. PMID- 7873944 TI - Euthanasia bill divides Australian doctors and MPs. PMID- 7873945 TI - Medical profession at last speaks out over abortion. PMID- 7873946 TI - Mortality from cardiovascular disease among interregional migrants in England and Wales. AB - OBJECTIVE: To investigate the extent to which geographical variations in mortality from ischaemic heart disease and stroke in Britain are influenced by factors in early life or in adulthood. DESIGN: Longitudinal study of migrants. SUBJECTS: 1% sample of residents in England and Wales born before October 1939 and enumerated at the 1971 census (the Office of Population Censuses and Surveys' longitudinal study). MAIN OUTCOME MEASURE: 18,221 deaths from ischaemic heart disease and 9899 deaths from stroke during 1971-88 were analysed by areas of residence in 1939 and 1971. These included 2928 deaths from ischaemic heart disease and 1608 deaths from stroke among individuals moving between 14 areas defined by the major conurbations and nine standard administrative regions of England and Wales. RESULTS: The southeast to northwest gradient in mortality from ischaemic heart disease was related significantly to both the 1939 area (chi 2 = 6.09, df = 1) and area in 1971 (chi 2 = 5.05, df = 1). Geographical variations in mortality from stroke were related significantly to the 1939 area (chi 2 = 4.09, df = 1) but the effect of area in 1971 was greater (chi 2 = 8.07, df = 1). The effect of 1971 area on mortality from stroke was largely due to a lower risk of death from stroke among individuals moving into Greater London compared with migrants to the rest of the South East region (chi 2 = 4.54, df = 1). CONCLUSIONS: Geographical variations in mortality from cardiovascular disease in Britain may be partly determined by genetic factors, environmental exposures, or lifestyle acquired early in life, but the risk of fatal ischaemic heart disease and stroke changes on migration between areas with differing mortality. The low risk of death from stroke associated with residence in Greater London is acquired by individuals who move there. PMID- 7873947 TI - Fetal and infant growth and cardiovascular risk factors in women. AB - OBJECTIVE: To examine whether cardiovascular risk factors in women are related to fetal and infant growth. DESIGN: Follow up study of women born 1923-30 whose birth weights and weights at one year were recorded. SETTING: Hertfordshire. SUBJECTS: 297 women born and still living in East Hertfordshire. MAIN OUTCOME MEASURES: Plasma glucose and insulin concentrations during a standard oral glucose tolerance test; fasting plasma proinsulin and 32-33 split proinsulin concentrations; blood pressure; fasting serum total, low density lipoprotein and high density lipoprotein cholesterol, triglyceride, and apolipoprotein A I and B concentrations; and plasma fibrinogen and factor VII concentrations. RESULTS: Fasting plasma concentrations of glucose, insulin, and 32-33 split proinsulin fell with increasing birth weight (P = 0.04, P = 0.002, and P = 0.0002 respectively, when current body mass index was allowed for). Glucose and insulin concentrations 120 minutes after an oral glucose load showed similar trends (P = 0.03 and P = 0.02). Systolic blood pressure, waist:hip ratio, and serum triglyceride concentrations also fell with increasing birth weight (P = 0.08, P = 0.07, and P = 0.07 respectively), while serum high density lipoprotein cholesterol concentrations rose (P = 0.04). At each birth weight women who currently had a higher body mass index had higher levels of risk factors. CONCLUSION: In women, as in men, reduced fetal growth leads to insulin resistance and the associated disorders: raised blood pressure and high serum triglyceride and low serum high density lipoprotein cholesterol concentrations. The highest values of these coronary risk factors occur in people who were small at birth and became obese. In contrast with men, low rates of infant growth did not predict levels of risk factors in women. PMID- 7873948 TI - Mortality among twins after age 6: fetal origins hypothesis versus twin method. AB - OBJECTIVE: To test the validity of the fetal origins hypothesis and the classic twin method. DESIGN: Follow up study of pairs of same sex twins in which both twins survived to age 6. SETTING: Denmark. SUBJECTS: 8495 twin individuals born 1870-1900, followed through to 31 December 1991. MAIN OUTCOME MEASURES: Mortality calculated on a cohort basis. RESULTS: Mortality among twins and the general population was not significantly different except among females aged 60-89, in whom mortality among twins was 1.14 times (SE 0.03) higher than in the general population. Mortality among female dizygotic twins was 1.77 times (0.18) higher than among monozygotic twins at age 30-59. Otherwise, mortality for monozygotic and dizygotic twins did not consistently differ after age 6. CONCLUSION: According to the fetal origins hypothesis the risk of adult morbidity and mortality is heightened by retardation in intrauterine growth. Twins, and in particular monozygotic twins, experience growth retardation in utero. The findings in the present study suggest that the fetal origins hypothesis is not true for the retardation in intrauterine growth experienced by twins. Furthermore, the data are inconsistent with the underlying assumption of a recent claim that the classic twin method is invalid for studies of adult diseases. The present study is, however, based on the one third of all pairs of twins in which both twins survived to age 6. The possible impact of this selection can be evaluated in future studies of cohorts of younger twins with lower perinatal and infant mortality. PMID- 7873949 TI - Predictors of ratio of placental weight to fetal weight in multiethnic community. AB - OBJECTIVE: To determine whether placental ratio is influenced by maternal ethnic origin, obesity, hypertension, and haematological indices of iron deficiency anaemia. DESIGN: Observational study. SETTING: District general hospital in Birmingham. SUBJECTS: 692 healthy nulliparous pregnant women, of whom 367 were European, 213 Asian, 99 Afro-Caribbean, and 13 of other or undocumented ethnic origin. MAIN OUTCOME MEASURES: Placental ratio and maternal body mass index, blood pressure, and haematological indices. RESULTS: Though birth weight and placental weight were lower in Asian women than in other groups, mean placental ratio was similar in Asian (19.5% (SD 3.3%)), European (20.0% (4.0%)), and Afro Caribbean women (20.4% (5.3%)). Gestational age at birth was the main predictor of placental ratio in the univariate analysis (r = -0.34, P < 0.001) and multivariate analysis. The only other significant predictor of placental ratio in multivariate analysis was maternal body mass index, which was positively associated with placental ratio (r = 0.1, P = 0.01). Mean (SD) placental ratio was not significantly higher in women who developed gestational hypertension (20.4% (4.5%)) and pre-eclampsia (23.3% (7.3%)) than in normal women (19.8% (3.8%)). No evidence of a relation between placental ratio and first antenatal visit haemoglobin concentration or mean cell volume was detected, and placental ratio was not associated with change in mean cell volume during pregnancy or with third trimester serum ferritin concentration. CONCLUSIONS: These data do not support the proposed association between poor maternal nutrition and increased placental ratio. The association between high placental ratio and adult hypertension may be confounded by genetic and environmental factors associated with maternal obesity (and possibly maternal hypertension). PMID- 7873950 TI - The NHS and Community Care Act 1990: is it a success for elderly people? PMID- 7873951 TI - Unreliability of reports of hypoglycaemia by diabetic patients. PMID- 7873952 TI - Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care. AB - OBJECTIVE: To determine whether, in the treatment of major depression in primary care, a brief psychological treatment (problem solving) was (a) as effective as antidepressant drugs and more effective than placebo; (b) feasible in practice; and (c) acceptable to patients. DESIGN: Randomised controlled trial of problem solving treatment, amitriptyline plus standard clinical management, and drug placebo plus standard clinical management. Each treatment was delivered in six sessions over 12 weeks. SETTING: Primary care in Oxfordshire. SUBJECTS: 91 patients in primary care who had major depression. MAIN OUTCOME MEASURES: Observer and self reported measures of severity of depression, self reported measure of social outcome, and observer measure of psychological symptoms at six and 12 weeks; self reported measure of patient satisfaction at 12 weeks. Numbers of patients recovered at six and 12 weeks. RESULTS: At six and 12 weeks the difference in score on the Hamilton rating scale for depression between problem solving and placebo treatments was significant (5.3 (95% confidence interval 1.6 to 9.0) and 4.7 (0.4 to 9.0) respectively), but the difference between problem solving and amitriptyline was not significant (1.8 (-1.8 to 5.5) and 0.9 (-3.3 to 5.2) respectively). At 12 weeks 60% (18/30) of patients given problem solving treatment had recovered on the Hamilton scale compared with 52% (16/31) given amitriptyline and 27% (8/30) given placebo. Patients were satisfied with problem solving treatment; all patients who completed treatment (28/30) rated the treatment as helpful or very helpful. The six sessions of problem solving treatment totalled a mean therapy time of 3 1/2 hours. CONCLUSIONS: As a treatment for major depression in primary care, problem solving treatment is effective, feasible, and acceptable to patients. PMID- 7873953 TI - Calculating correlation coefficients with repeated observations: Part 1- Correlation within subjects. PMID- 7873954 TI - The number needed to treat: a clinically useful measure of treatment effect. AB - The relative benefit of an active treatment over a control is usually expressed as the relative risk, the relative risk reduction, or the odds ratio. These measures are used extensively in both clinical and epidemiological investigations. For clinical decision making, however, it is more meaningful to use the measure "number needed to treat." This measure is calculated on the inverse of the absolute risk reduction. It has the advantage that it conveys both statistical and clinical significance to the doctor. Furthermore, it can be used to extrapolate published findings to a patient at an arbitrary specified baseline risk when the relative risk reduction associated with treatment is constant for all levels of risk. PMID- 7873955 TI - Events per person year--a dubious concept. AB - In 1982 a new measure was introduced in research into osteoporosis and is now used everywhere in the literature. The so called "fracture rate" relates the number of fractures (single in some patients, multiple in others) to the cumulative time of observation of all patients. This concept, however, has no sound basis. Counting events instead of patients usually violates basic statistical assumptions and invalidates the use of common statistical tests and estimators. Its clinical interpretation is rather dubious. The use of such a measure impedes the search for valid and clinically meaningful outcome criteria and should be abandoned. PMID- 7873956 TI - ABC of rheumatology. Osteoarthritis. PMID- 7873957 TI - Methadone maintenance treatment. Britain has been overcommitted to psychological theories of drug dependence. PMID- 7873958 TI - Methadone maintenance treatment. Methadone treatment can reduce mortality. PMID- 7873959 TI - Methadone maintenance treatment. Patients on methadone often continue with injected heroin. PMID- 7873960 TI - Methadone maintenance treatment. Pregnant women taking methadone should be warned about withdrawal symptoms in babies. PMID- 7873961 TI - Methadone maintenance treatment. We don't know whether heroin or methadone produces more withdrawal symptoms in babies. PMID- 7873962 TI - Methadone maintenance treatment. Glasgow has an innovative scheme for encouraging GPs to manage drug misusers. PMID- 7873963 TI - Auditing incidents of exposure to blood. PMID- 7873964 TI - Management of ventricular fibrillation by cardiac arrest teams. PMID- 7873965 TI - Treatment of myocardial infarction and angina. Advice on reducing cholesterol should be included. PMID- 7873966 TI - Risk of coronary heart disease in Asian women. PMID- 7873967 TI - Diagnosing pulmonary embolism. PMID- 7873968 TI - Temperature and cardiovascular mortality. PMID- 7873969 TI - Interpretation of electrocardiograms. Interpretation of the ECG is as much an art as a science. PMID- 7873970 TI - Continuous ambulatory electrocardiography in elderly people. PMID- 7873971 TI - Weight in infancy and coronary heart disease in adult life. PMID- 7873972 TI - Simple aspiration for spontaneous pneumothorax. PMID- 7873973 TI - Doctors and management. PMID- 7873974 TI - Reform of GMSC not needed. PMID- 7873975 TI - Failure of consultant expansion. Consultant expansion depends on local cooperation. PMID- 7873976 TI - Failure of consultant expansion. Expansion depends on rigorous control of numbers in training and non-consultant career grades. PMID- 7873977 TI - Mortality and alcohol consumption. PMID- 7873978 TI - Cell receptors: definition, mechanisms and regulation of receptor-mediated endocytosis. AB - Receptors allow the cells to recognize specific ligands and to receive extracellular messages. They can be classified into five families: 1) receptors for lipidic or lipophilic ligands; 2) the seven transmembrane receptors which mediate their messages by transduction through the activation of G-proteins, effectors and second messengers to amplify the response; 3) receptors which present an enzymatic activity on their transmembrane domains; 4) channel receptors, transmembrane oligomeric molecules which let ions flow into the cell and 5) receptors which role is to internalize ligands, whatever their various functions. In parallel a concept of membrane plasticity was developed: vesicles are constantly formed from the plasma membrane, addressing complexes of ligand receptors to specific intracellular compartments. This receptor-mediated endocytosis of ligand plays a critical role in regulating the number of a given receptor at the plasma membrane and in the cellular uptake of nutrients, growth factors and hormones. Many pathways exist for these transports but little is known about the signals which select the ligands or the receptors and direct them to their appropriate intracellular destination. PMID- 7873979 TI - Effects of Di-(2-ethylhexyl)phthalate on peroxisomes of liver, kidney and brain of lactating rats and their pups. AB - Di-(2-ethylhexyl)phthalate administered to adult lactating rats, from delivery to weaning, induces modifications of the peroxisomal enzymatic pattern in the liver, kidney and brain of both dams and pups. These modifications are age- and organ dependent. Biochemical analysis shows that: 1) catalase specific activity is two fold increased in the liver of both adult and newborn animals, in the kidney of newborns and in the brain of adults. 2)D-amino acid oxidase doubles in all newborn organs and in adult brain; it increases, although to a lesser extent, also in adult kidney, while it is half-reduced in adult liver. 3) Dihydroxyacetone phosphate acyl transferase only doubles in newborn liver, remaining fairly unchanged in all the other tested tissues. 4) Palmitoyl-CoA oxidase is greatly induced in the liver of both dams and litters, doubled in the kidneys and slightly increased or not at all in the brain of pups and mothers, respectively. The effect of the drug on enzyme activities is reversible, with different time courses depending on the considered enzyme and organ. Western blottings confirm the biochemical data. Electron microscopy shows proliferated peroxisomes in the liver and kidney of treated animals but not in the brain, where high catalase-like immunoreactivity is observed in the cytosol of neurons. Taken together, our data demonstrate that the response of peroxisomal enzymes to DEHP treatment is age- as well as tissue-dependent and specific for each enzyme studied. PMID- 7873980 TI - Is the brush border membrane of the intestinal mucosa a generator of "chymosomes"? AB - 1. The microvilli of enterocytes in calf intestine demonstrate high levels of vesiculation activity at the top and at the basal region. 2. The morphology of the vesicles associated with microvilli (100-500 nm diameter, unilamellar, few intramembraneous particles, high AP activity) is very similar to the morphology of vesicles found in the chyme. 3. Vesicles can be purified 6-10 fold from chyme of the calf intestine applying a Mg(++)-precipitation method, used for brush border membrane preparation. 4. Specific activities of alkaline phosphatase and disaccharidases were found to be much higher in chyme vesicles than in the mucosa. 5. Phospholipid content and phospholipid composition is in chyme vesicles different from brush border membrane vesicles. 6. The characterized chyme vesicles are referred to as chymosomes. We consider the mucosa as a large-scale generator of chymosomes, i.e. digestive enzymes bearing vesicles. PMID- 7873981 TI - Localization of ZP3 mRNA in mouse ovary by non-radioactive in situ hybridization with digoxigenin-labelled cDNA. AB - In situ hybridization using digoxigenin-labelled cDNA has dual advantages of having high structural resolution and high sensitivity and avoiding problems associated with the handling of radioactive materials. We have used this technique to detect and locate mRNA for mouse ZP3 protein in paraffin sections of fixed ovaries of newborn and adult mice. Mouse ZP3 mRNA was restricted to the cytoplasm of oocytes. After day 16, ZP3 mRNA expression was increasingly restricted to the cytoplasm of the oocyte. Previous work on the distribution of ZP3 mRNA was confirmed and we were able to show that using non-isotopic in situ hybridization, sensitive and accurate cellular localization was feasible in paraffin embedded mouse ovary. PMID- 7873982 TI - Hepatocyte growth factor is a potent promoter of mitogenesis in cultured rat visceral glomerular epithelial cells. AB - Hepatocyte growth factor (HGF) was originally identified as an hepatotrophic factor inducing liver regeneration, and was also recently found to stimulate mitogenesis of various epithelial cells. In the present study, we examined the mitogenic effects of native and recombinant HGF on cells of rat visceral glomerular epithelial cell line (SGE1). Native and recombinant HGF each stimulated DNA synthesis in and growth of SGE1 cells to a remarkable degree. These mitogenic activities were dose-dependent, being detectable at 2.5 ng/ml and maximal at 20 ng/ml. Over 30% of SGE1 cells tested were shifted to S-phase by HGF alone, as judging by labeling index values. DNA synthesis stimulated by native or recombinant HGF was high at low SGE1 cell density and was strongly suppressed at high cell density. DNA synthesis in and growth of SGE1 cells were stimulated more strongly by recombinant HGF than by native HGF. In addition, the effects of recombinant HGF and epidermal growth factor were additive, while transforming growth factor-beta 1 strongly inhibited the stimulation of DNA synthesis by recombinant HGF. These findings suggest that HGF may play a role in controlling visceral glomerular epithelial cell growth. PMID- 7873983 TI - Dysmorphic erythrocytes in glomerulonephritis. 1. Electron microscopical and histochemical investigation. AB - Dysmorphic erythrocyte malformation in urine is characteristic of glomerulonephritis. The mechanisms leading to this phenomenon are still unknown. To obtain evidence of the site as well as of the process of erythrocyte damage, electron microscopical and histochemical investigations of renal biopsy materials from 19 patients with histologically defined glomerulonephritis were performed. The results suggest that the initial damage of erythrocytes in the glomerular area is reasoned by enzymatic glycocalyx destruction. On passage through the tubular system the osmotically sensitized surface altered cells undergo rapid hemolysis and losses of membrane skeletal proteins leading to dysmorphic shape transformations. PMID- 7873984 TI - Dysmorphic red cell formation in glomerulonephritis. 2. In vitro generation of dysmorphic erythrocytes. AB - In the present study influences leading to in vitro formation of dysmorphic erythrocytes were studied. Fresh and surface altered erythrocytes pretreated with several proteases were passed through different solutions representing distinct nephronis fluids. After passage of intact erythrocytes only 12-15% dysmorphic cells were observed. In case of protease treated cells the number of dysmorphic cells rose to 35-80%. The hemoglobin content was decreased. PAGE and electron microscopical findings demonstrated substantial losses of transmembrane and membrane skeleton proteins. It is assumed that surface protein degradation, loss of membrane skeleton proteins and hemolysis seem to be closely associated with dysmorphic malformation of urinary erythrocytes characteristical for glomerulonephritis. PMID- 7873985 TI - The in vitro proliferation of thymus epithelial cells stimulated with growth hormone and insulin-like growth factor-I. AB - The experimental system to scrutinize the in vitro proliferation of thymus epithelial cells (TECs) was established on the basis of enhancing their mitotic index and DNA synthetic activity. The TEC line, TAD3 derived from lymphocyte dominant thymoma, was used as the cell material. Growth hormone (GH) induced a significant proliferation of the cultured cell line in the preconfluent state. The optimal concentration of and the duration of the incubation with GH, in this system, were 50 ng/ml and 18 hrs., respectively. Furthermore, insulin-like growth factor-I (IGF-I), the mediator of somatotropic action of GH, also enhanced the DNA synthetic activity of the cultured cells in the preconfluent state. The authors recently found that the TECs, stimulated with GH, released significantly more IGF-I than the cells without GH. It is possible that there are two systems in the TEC proliferation, namely, direct induction by GH itself and indirect induction by IGF-I released from the GH-stimulated TECs. The data showing that GH could directly or indirectly induce proliferation of TECs might possibly be related to the formation of epithelial thymic rudiment in the fetal stage. PMID- 7873986 TI - The gene encoding lactoperoxidase is expressed in epithelial cells of the goat lactating mammary gland. AB - The localization of lactoperoxidase (LP), which catalyzes in milk the peroxidation of endogenous thiocyanate in the presence of peroxide, was investigated in the goat lactating mammary gland, using immunofluorescence and hybridization techniques. In situ hybridization experiments have demonstrated the presence of LP mRNA within the cytoplasm of alveolar epithelial cells (acini) where LP has been detected by immunofluorescence labelling with anti-LP polyclonal antibodies. Taken together, these data provide the first direct evidence for expression of the LP gene within secretory cells of the lactating mammary gland. PMID- 7873987 TI - Ultrastructural and histochemical changes of mitochondria in global ischemic cardiac muscle of rat. AB - Ultrastructural changes of mitochondria and histochemical changes of the cytochrome oxidase of mitochondria during global ischemia and in reperfused rat heart were observed under transmission electron microscope. The ultrastructural changes of mitochondria were evaluated by scoring the mitochondrial damages and by densitometry of the mitochondria as a marker of the density of the granules of the mitochondrial matrix. For demonstrating the cytochrome oxidase activity, 3,3' diaminobenzidine (DAB) reaction was used. Histochemical modifications of the cytochrome oxidase activities were evaluated by using a scoring system of localization of the cytochrome oxidase and by densitometry of the mitochondria. In the ischemic groups, ultrastructural changes, such as a decrease of mitochondrial matrix granules and disruption of cristae, were observed from 60 min. ischemia. However, no particular ultrastructural changes were observed from 60 min. to 240 min. ischemia. In reperfusion, after 60 min. ischemia, the ultrastructures were recovered, but they were not recovered in reperfusion after 120 min. ischemia. The cytochrome oxidase activities did not change until 120 min. ischemia. However, in 240 min. ischemic groups the cytochrome oxidase was sparsely localized. Histochemical changes of cytochrome oxidase activities may lag behind the ultrastructural changes of mitochondria. PMID- 7873988 TI - Inhibitor effects on the ionic exchanges through the human amniotic epithelial cell membranes. AB - Direct measurements of cell podocyte/or microvillous membrane ionic exchanges were performed on the membranes of isolated human amniotic epithelial cells. The ionic exchanges were determined from the measures of cellular input conductances. The effects of various inhibitors: ouabain, amiloride, 4-acetamido-4' isothiocyanostilbene-2,2'-disulfonic acid (SITS), 4'4'-diisothiocyanostilbene 2,2'-disulfonic acid (DIDS), quinidine, barium, manganese were analyzed. This study shows that the ionic exchanges through the epithelial cells are regulated by the presence of Na+,K+,Cl- channels, Na+/H(+)-Cl-/HCO3- antiports, (Na K)ATPase and Na+/Ca(2+)-Na+/Mg2+ exchangers on the 2 faces of the cells and of a Na(+)-K(+)-2Cl- cotransport on the membrane facing the amniotic cavity only. PMID- 7873989 TI - High resolution (SE-I) scanning electron microscopy features of primate cerebellar cortex. AB - This paper provides an exploration into the outer and inner surfaces of primate cerebellar neurons using secondary electron-I (SE-I) topographic contrast. SE-I enriched, chromium coated, cryofractured cerebellum staged within the condenser/objective lens stage of SEMs, equipped with high brightness LaB6 and field emission emitter, generated quality images of intact and fractured nerve cells studied at intermediate and high magnifications. Granule and Golgi cell surfaces revealed smooth, accurately delineated profiles of the true cell surface features, which lacked the SE-III dominated brilliance of conventional gold or gold-palladium decorated images. Fractured non synaptic segments of parallel fibers in the molecular layer showed interconnected anastomotic networks of ER tubules, vesicles and cisterns, whereas cross fractured presynaptic "en passant" endings of these fibers exhibited spheroidal synaptic vesicles and SE-I edge brightness contrast delineated their limiting plasma membranes. Parallel fiber fractured synaptic endings showed a homogeneous extravesicular material surrounding the synaptic vesicles. The neuroglial cytoplasm ensheathing nerve processes exhibited a smooth discontinuous surface. The high mass density surface of the myelin sheath showed a mixed population of globular structures, 10-30 nm, corresponding to protein and phospholipid microdomains. PMID- 7873990 TI - Inhibition of mouse parenchymal cells proliferation by mosquito larvae extract. AB - As it is known, some cell populations of mosquito Aedes aegypti larvae do not proliferate. This fact suggests the existence of some mitosis inhibiting factor. We have assayed the effect of mosquito larvae crude extract on 85 C3HS young male mice (25 +/- 1 days old) and the effect of the dialyzed fraction of the same extract on 47 partially hepatectomized C3HS adult male mice. The injection was performed at 16:00 hour (before the raising of the DNAS curve) and the controls were made at 08:00/16, 12:00/20 and 16:00/24 (Time of Day/Time Post Injection). Colchicine arrested metaphases of nephrocytes, hepatocytes, sialocytes (submaxillary glands) and enterocytes were controlled. The mitotic rate was significantly inhibited in hepatocytes, sialocytes and enterocytes in young growing mice, and in hepatocytes in partially hepatectomized adult mice. We conclude that TGF-beta, actually found in insects, or alternatively some other known or unknown factor, could be responsible for the results observed in the present experiments. PMID- 7873991 TI - Modulation of contractile protein troponin-T in chick myocardial cells by catecholamines during development. AB - In the present study we quantified the contractile protein troponin-T at the cellular and subcellular level in chick embryo cardiomyocytes to investigate the modulation of cardiac development by catecholamines. We analyzed the effects of these drugs on cultures of chick cardiomyocytes obtained from Hamburger and Hamilton's (HH) stage 21, HH stage 29 and HH stage 40 embryos; cardiomyocytes are considered to be mature at HH stage 40. We analyzed the modifications these drugs induced in the transcription of the gene for chick cardiac troponin-T. Sodium dodecyl sulfate-gel electrophoresis and immunobloting showed that cytoplasmic and cytoskeletal concentrations of troponin-T are dependent on the stage of embryonic development analyzed, and on the type of catecholamine added to the culture. The most significant finding was the increase in troponin-T mRNA in the chick heart at HH stage 40, accompanied by an increase in the increase in the expression of this protein in the cytoskeletal compartment after treatment with norepinephrine. At HH stage 21, norepinephrine induced less marked changes in the accumulation of troponin-T in comparison with untreated cardiomyocytes. PMID- 7873992 TI - The effects of stress on lipoproteins and catecholamines in rats. AB - In order to investigate the effects of transportation stress on metabolic activities, we measured the changes in plasma lipoprotein and catecholamine levels in those rats that had just arrived in our Animal Facility and age-matched rats which had acclimatized in the Facility for at least 21 days. The acclimatized rats were considered as control, and the values from the newly arrived rats was done within 4-6 days of their arrival in the Facility. The cholesterol levels in very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) were higher (71-84%) than the control levels. Also, the stressed animals had higher levels of norepinephrine (4.5-fold) and epinephrine (3-fold) than the control levels. However, dopamine levels was 34-fold lower than that of control. On the basis of the data, we concluded that the change in plasma levels of lipoprotein and catecholamines in response to the transportation stress is significant and may require at least three weeks after the transportation to establish a stable baseline for investigations in which the plasma levels of lipoproteins and catecholamines is a critical factor. PMID- 7873993 TI - Glucocorticoid receptors and resistance to glucocorticoids in hematologic malignancies. AB - Glucocorticoids are highly effective in inducing the cytolysis of cells of lymphocytic origin. This property has resulted in their incorporation into chemotherapy regimens used in the treatment of hematologic malignancies. Studies at the molecular and cellular levels have demonstrated that the hormone-induced cytolytic response is mediated through a highly specific cytoplasmic glucocorticoid receptor (GR). The GR has been cloned and sequenced and found to be organized into a discrete series of domains which mediate the receptor functions of hormone binding, nuclear translocation, DNA binding and transcriptional modulation. Thus, the binding of glucocorticoids by the GR induces a series of cellular events which result in the activation or repression of a network of glucocorticoid responsive genes and produces a specific cellular response. Prolonged exposure to glucocorticoids ultimately causes resistance to develop; thereby limiting the usefulness of this class of drugs. Studies addressing the mechanism of resistance have shown that the GR is the primary target of genetic alterations that lead to resistance to cytolysis. Using mouse and human cell lines as model systems, it has been shown that the vast majority of glucocorticoid resistant mutants express low levels or altered forms of the GR. Similarly, in vivo studies on patients have suggested that low GR levels are associated with a poor response to glucocorticoid based therapies. Recently, aberrant GR isolated from a patient with multiple myeloma resistant to glucocorticoids were found to harbor deletions in their hormone binding domains. Sequencing of the receptors suggested that each arose as a result of alternate splicing events. In both cases, the latter event produces a receptor unable to bind hormone leading to the speculation that alternate splicing may serve as a mechanism by which a cell evades the effects of glucocorticoids. The therapeutic implications for patients expressing aberrant receptors is discussed. PMID- 7873994 TI - Prognostic factors in myeloma: what they tell us about the pathophysiology of the disease. AB - Prognostic factors in myeloma are not only important for allowing comparisons to be made between therapeutic protocols but they also provide us with an insight into the pathophysiology of the disease and important mechanisms which result in disease progression. Prognostic factors in myeloma relate to the inherent proliferative capacity of the malignant clone, tumor bulk, renal function and other factors which reflect tumor host and host tumor interactions. The highly significant effect of the labelling index (LI) suggests that the clonogenic cell is ontologically very close to the malignant plasma cell on which the labelling index is derived. The explanation for the important role of the beta 2 microglobulin (beta 2M) level over and above its reflection of renal function is as yet unclear. Other factors involved in prognosis such as serum cytokines (IL-2 and IL-6) and soluble IL-6 receptor levels reflect host tumor interactions. An understanding of these interactions may allow us to control the disease and prevent escape from plateau phase by biological means. This may become a viable alternative to high dose aggressive chemotherapy which up till now appears unable to eradicate the malignant clone. PMID- 7873995 TI - The potential role of cytokines in the pathogenesis of Epstein-Barr virus associated post-transplant lymphoproliferative disease. AB - Post-transplant lymphoproliferative disease (PTLD) is a complication of Epstein Barr virus infection occurring in immunosuppressed transplant recipients. Non clonal lesions with a polymorphous histology have the potential of regressing, if the degree of immunosuppression is reduced, thereby giving the immune system a chance to recuperate. In contrast, clonal tumors with a monomorphous histology portend a bad clinical outcome. This review summarizes evidence that the biological behavior of PTLD may be predicated on intercellular interactions involving multiple cytokines. With further investigations to clarify the nature of these interactions, it should be possible to design rational strategies for the cytokine therapy of human PTLD. PMID- 7873996 TI - A strategy for precision of genotyping of Epstein-Barr virus by polymerase chain reaction: application for studying Hodgkin's lymphoma. AB - Previous studies on the genotyping of Epstein-Barr virus (EBV) have been based on the analysis of a single gene locus. The assignment of genotype of an isolate could easily be over-looked with this assay. Our strategy for precision of EBV genotyping has exploited the existence of two families of EBV strains (type A and B) that can be distinguished at three divergent gene loci (EBNA-2, EBNA-3C, and EBER). To precisely determine the genotype of EBV in Hodgkin's disease (HD), we designed primers and simultaneously analysed these three gene loci that distinguish type A and B viruses by the polymerase chain reaction (PCR) technique. The primers designed to amplify these three gene loci encompass either type-specific deletion sequences (EBNA-2 and EBNA-3C) or type-specific point mutations (EBER) that identify the virus strain based on the sizes of PCR amplified products or the mobility shifts in single-strand conformation polymorphism (SSCP) analysis. The locations of point mutations were identified by direct sequencing of the PCR-amplified DNA. Fifteen EBV-infected cell lines were analysed and a good correlation between EBNA-2 and EBNA-3C typing results was found. In contrast, approximately 33% of the cell lines analysed maintained type A sequences in EBNA-2 and EBNA-3C genes while carrying type B sequences in the EBER region. Data obtained from analysis of cell lines served as a reference for studying HD samples. EBV DNA was detected in about 70% of HD. Among the EBV positive samples, 56% were associated with type A virus, 13% with type B, and 31% with dual viral sequences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7873997 TI - Expression of human recombination activating genes (RAG-1 and RAG-2) in lymphoma. AB - Two recently discovered genes, the recombination activating genes 1 and 2 (RAG-1 and RAG-2), are necessary to perform variable (V), diversity (D), and joining (J) recombination. They synergistically activate VDJ recombination to generate immunocompetent lymphocytes. Disruption of either gene results in a maturation arrest at a very early B and T cell progenitor stage. Expression and downregulation of RAG's are closely associated with interleukin 7, sIgM and TCR CD3 complex, respectively. Assessment of RAG mRNA expression is a valuable marker in identifying the genotypic maturation status of leukemias and lymphomas. Persistent RAG expression in otherwise mature lymphoid proliferations may explain puzzling biological and clinical observations such as multiple rearrangements in lymphomas with a mature phenotype. Lack of RAG expression in Hodgkin's disease with abundant Reed-Sternberg cells is consistent with a mature phenotype of the latter. Availability of a anti-RAG-1 monoclonal antibody in the near future will facilitate RAG analysis of lymphomas. PMID- 7873998 TI - Cytokines and cytokine receptors in acute lymphoblastic leukemia expressing myeloid markers--role in growth regulation. AB - There is no evidence that cancer cells including leukemic cells are immortal. It has been clearly indicated that certain cytokines can significantly stimulate leukemic cell proliferation in vitro, and sustain the circuit of autocrine or paracrine stimulation. The biological roles of cytokines and cytokine receptors have been intensively investigated in acute leukemia. Recently coexpression of both lymphoid and myeloid features on a single leukemic cell has been well recognized using a flowcytometric technique. Studies of ALL cells expressing myeloid markers (My+ ALL) have indicated that the profiles of cytokines and cytokine receptors expressed by My+ ALL show both similarities and differences to those in My- ALL or acute myelogenous leukemia (AML), suggesting that My+ ALL cells may originate from uncommitted hematopoietic precursor cells coexpressing features of both lymphoid and myeloid lineages. The exact assessment of cytokine response of leukemic cells would provide an important tool for phenotyping acute leukemia based on the growth properties of the cells (cytokine phenotyping), in addition to the morphologic classification and immunological surface phenotyping. Additionally alteration of sensitivity to cytotoxic anticancer drugs by cytokine stimulation may be the new strategy for biologic therapy of acute leukemia. PMID- 7873999 TI - The hematopoietic stem cell transplantation in Hodgkin's disease: questions and controversies. AB - Most patients with Hodgkin's disease (HD) are cured with chemotherapy and/or radiotherapy. However, half of those with advanced stage disease (IIIB, IV) do not respond adequately to treatment or relapse. Salvage therapy used in such cases gives from 10% to 50% complete remission but only 10% long term survival. The results of bone marrow transplantation reported in acute leukemia and non Hodgkin's lymphoma encouraged some authors to develop this new therapeutic strategy in Hodgkin's disease. In the early 1980's promising results were achieved when refractory and relapsed patients were selected to receive myeloablative therapy followed by bone marrow transplantation. Today, high dose chemotherapy with hematopoietic stem cell transplantation (HSCT) is used more and more often in poor prognosis Hodgkin's disease. After a review of the literature concerning the results of transplantation in Hodgkin's disease, we develop the numerous problems associated with this procedure which remain to be solved such as: the optimal indication, the timing of HSCT, the type of graft, the conditioning regimen, the place of radiotherapy and the optimal use of hematopoietic growth factors. We conclude with future prospects. PMID- 7874000 TI - Early cytoreduction: a major prognostic factor in adult acute lymphoblastic leukemia. AB - Prognostic factors in acute lymphoblastic leukemia (ALL) are used for treatment stratification of ALL. Definition of simple parameters such as the presence or absence of peripheral leukemic cells after one week of treatment could help for stratification. A retrospective study was conducted on 79 previously untreated adult patients with ALL followed in the Hematology department of Hotel Dieu from 1981 to 1991. 84% of patients achieved complete remission (CR), 7% were refractory to induction treatment, and 7 patients (9%) died during the first month after diagnosis. After multivariate analysis the only independent statistically significant factors for achieving CR were the absence of peripheral blast cells at day 7 (PBC D7) (p = 0.009) and age (< 50 years) (p = 0.03). For CR duration the same independent statistically significant factors were found (PBC D7 = 0 versus > 0, p = 0.008; and age < or > or = 30 years, p = 0.045). The PBC D7 value was more significant when circulating blast cells were present at diagnosis. In patients with more than 50,000 PBC at diagnosis, the 10- years event free disease was 62% +/- 20% when PBC were absent at day 7 versus 0% when PBC were present (p < 0.002). All 20 patients with prolonged DFS had PBC D7 = 0 achieving CR by 28 days. The persistence of PBC at Day 7 could be used as a factor to identify a subgroup of poor prognosis adults with ALL. PMID- 7874001 TI - Drosophila Forkhead homologues are expressed in CD34+/HLA-DR- primitive human hematopoietic progenitors. AB - The Forkhead gene (FKH) regulates morphogenesis in Drosophila. It is the prototype of a new family of transcriptional activators. We used the polymerase chain reaction (PCR) to analyze the expression pattern of this new transcriptional regulatory gene family in primitive hematopoeitic progenitors. Partially degenerate oligonucleotides to two conserved amino acid sequences of this family were used to prime a PCR amplification of cDNA synthesized from CD34+/HLA-DR- hematopoietic cells. Known and novel FKH genes were found to be expressed in these cells. PMID- 7874002 TI - Combined antileukemic activity of pIXY 321 and Ara-C against human acute myeloid leukemia cells. AB - Prolonged administration of conventional (100 mg/m2/day) or low dose Ara-C (20 mg/m2/day) has been associated with significant clinical antileukemic effects in AML and myelodysplastic syndromes. These doses and schedules of Ara-C yield plasma Ara-C concentrations in the range of 10 to 100 nM. Utilizing concentrations and a schedule of Ara-C treatment, representative of Ara-C exposures in these clinical situations, we performed in vitro studies to examine the effects of co-treatment with pIXY 321 on Ara-C induced apoptosis and Ara-C mediated colony growth inhibition of human myeloid leukemia HL-60 cells. Significantly greater internucleosomal DNA fragmentation, higher percentage of morphologically recognizable apoptotic cells and increased colony growth inhibition were observed following treatment with 100 versus 10 nM Ara-C for 5 days. Simultaneous exposure to 10 ng/ml pIXY 321 resulted in significantly increased colony growth inhibition as well as DNA fragmentation and apoptosis due to 10 nM but not 100 nM Ara-C. These concentrations of Ara-C inhibited c-myc and did not induce c-jun mRNA expression. These effects of Ara-C on c-myc and c-jun expressions were not influenced by co-treatment with pIXY 321. Neither treatment with pIXY 321 or Ara-C alone, nor co-treatment with pIXY 321 and Ara-C, significantly altered the intracellular p26BCL-2 levels in HL-60 cells. These results indicate that co-treatment with pIXY 321 significantly increases low dose Ara-C-induced apoptosis and thereby its antileukemic activity. PMID- 7874003 TI - Evaluation of the clinical relevance of the anionic glutathione-s-transferase (GST pi) and multidrug resistance (mdr-1) gene coexpression in leukemias and lymphomas. AB - By using RNA slot-blot technique, the frequency and the degree of GST pi and mdr 1 gene coexpression were investigated in 23 AML patients, 9 ALL, 9 CLL and 11 cases of NHL in an attempt to study their clinical and prognostic relevance. GST pi and mdr-1 levels were expressed as arbitrary units (U) with respect to the negative controls (U = 0), MCF7 and HL60 sensitive cell lines, and the positive controls (U = 10), MCF7/DOXO and HL60/DNR resistant cell lines. The concomitant GST pi/mdr-1 gene overexpression showed a negative prognostic value in the set of newly diagnosed AML pts (10 cases), furthermore higher GST pi and mdr-1 mRNA levels were averagely detected in the relapsed/resistant ALL pts (4 cases), and in CLL (7 cases) and NHL (8 cases) heavily pretreated patients who were unresponsive to chemotherapy and with a disease progression. These preliminary data show that two different mechanisms of drug resistance can be coexpressed at the same time in those leukemias and lymphomas with a clinically unfavourable course. PMID- 7874004 TI - Clonal analysis of Hodgkin's disease shows absence of TCR/Ig gene rearrangement, compared with T-cell-rich B-cell lymphoma and incipient adult T-cell leukemia/lymphoma. AB - To better characterize the clonality and pathogenesis of Hodgkin's disease (HD), we used polymerase chain reaction (PCR) and Southern blot to analyze the rearrangement of immunoglobulin (Ig) and T-cell receptor (TCR) genes, the bcl-2 oncogene, and the Epstein-Barr virus (EBV) genotype. In situ hybridization studies of EBV were also done. Twenty-six cases of HD were compared with 15 cases of non-specific lymphadenitis, 7 with incipient adult T-cell leukemia/lymphoma (ATLL), and 4 T-cell rich B-cell lymphomas (TRBL), all of which histologically resembled HD. EBV genes were detected in 20 of 26 HD patients (77%) and in 7 of 15 patients with non-specific lymphadenitis (47%), 5 of 7 with incipient ATLL (71%), and 1 of 4 with TRBL (25%). In contrast to specimens of non-specific lymphadenitis, TRBL, and incipient ATLL, only one EBV genotype was evident in the specimens of HD. EBV latent membrane protein (LMP) was detected immunologically in 16 of 26 HD patients (62%), one of four TRBL (25%) and one of seven incipient ATLL (14%), but it was not evident in non-specific lymphadenitis. The LMP positive cases showed amplified EBV genomes. Only one of the 26 cases of HD had a bcl-2 gene rearrangement by PCR, but this was not seen in any other disease. The bcl-2 protein was detected immunologically in seven of the 26 HD patients (27%) and in one of the seven incipient ATLL cases (14%). EBV has been reported to upregulate bcl-2 expression, but in this study the presence of bcl-2 protein did not correlate with the presence of the t(14;18) translocation or EBV-LMP. All TRBLs showed rearrangement of the immunoglobulin genes by PCR and/or Southern blot, and the giant cells were of B-cell type. All incipient ATLLs displayed rearrangement of the TCR genes, and the giant cells were of T-cell origin. In seven of 26 HD cases, the giant cells were weakly stained with T-cell antibodies, in another seven positive with B-cell antibodies and in 18 instances polyclonally positive for both kappa and lambda. However, PCR and Southern blot displayed only two cases of TCR gene rearrangement, while two others had very weak rearrangements of immunoglobulin gene positive only by PCR. Thus the T and B-cell genotype did not correlate with the T and B-cell phenotype recorded in these cases. The absence of Ig and TCR gene rearrangements seems to be common in HD, compared with in TRBL and incipient ATLL. PMID- 7874005 TI - Mitoxantrone, chlorambucil and prednisolone in the treatment of non-Hodgkin's lymphoma. AB - The management of low grade lymphoma, both de novo and relapsed disease, is a contentious area in which there has been little real progress in recent years. Regimens which increase the intensity of treatment may accelerate the response but are inevitably associated with greater toxicity. This cannot be justified in a disease whose median survival is between 4 and 10 years and where the median age at presentation is 57. We have assessed the response of 144 patients treated with a combination of mitoxantrone, chlorambucil and prednisolone in a heterogeneous group with lymphoma, both de novo and relapsed disease. In the subgroup with low grade relapsed/refractory disease our results suggest that this combination is clinically effective, low in toxicity and suitable for the outpatient management of this usually elderly patient population. PMID- 7874006 TI - Paraneoplastic neurological syndromes associated with lymphomas. AB - We describe two patients who developed paraneoplastic neurological syndromes and have reviewed the literature. One patient with Hodgkin's disease developed brachial neuritis. The other with a non Hodgkin's lymphoma of thyroid suffered from ataxia owing to cerebellar degeneration. Both neurological syndromes developed following marked nodal shrinkage following chemotherapy. Although both patients are in complete remission there has been no recovery of the neurological deficit. The patient with brachial neuritis developed L'hermitte's sign after a modest dose radiation (35Gy in 20 fractions) to the cervical cord and a vincristine sensory neuropathy. Vincristine may also have increased the degree of ataxia in the second patient. We suggest that potentially neurotoxic treatment should be given with extra care to patients with paraneoplastic neurological disorders. PMID- 7874007 TI - Myelodysplastic syndrome with bone marrow eosinophilia: clinical and cytogenetic features. AB - We investigated the hematological and clinical status of 145 patients with de novo myelodysplastic syndrome (MDS), 14 of whom (10%) had eosinophilia in the bone marrow (MDS-Eo). Most of these 14 patients had severe anemia. Their bone marrow cells exhibited trilineage dysplasia and some morphological abnormalities in the eosinophils, including disproportion of eosinophilic granules, basophilic granules, a ring-shaped nucleus, and vacuolation in the cytoplasm. However, these abnormalities were less prominent than those of acute myelomonocytic leukemia with eosinophilia (FAB: M4Eo). Three of the 14 MDS-Eo patients had refractory anemia (RA), seven had RA with excess of blasts (RAEB), and four had RAEB in transformation. Cytogenetic analysis revealed chromosomal abnormalities in 12 of 13 MDS-Eo patients (92%), in particular, there were major karyotypic abnormalities (MAKA) in eight patients (62%). Cytotoxic agents were not effective in the treatment of four patients after leukemic transformation occurred. These four patients died of the leukemic transformation while seven died of bone marrow failure. The other three MDS-Eo patients are still alive; two of them have already transformed to a leukemic phase. The duration of survival of these patients was significantly shorter than that of the other MDS patients. These findings suggest that bone marrow eosinophilia in MDS may be a poor prognostic factor that is strongly related to the existence of MAKA. PMID- 7874008 TI - Plasma urokinase-type plasminogen activator in patients with leukemias. AB - Plasma levels of urokinase-type plasminogen activator (u-PA) were measured with an enzyme-linked immunosorbent assay in patients with leukemias. As compared with healthy subjects (0.73 +/- SD 0.17 ng/ml), plasma u-PA antigen level was markedly elevated in patients with acute promyelocytic leukemia (APL) (1.76 +/- 0.89 ng/ml) at disease onset. Mean u-PA concentrations in patients with other acute nonlymphoblastic leukemia (0.57 +/- 0.51 ng/ml), acute lymphoblastic leukemia (0.77 +/- 0.82 ng/ml) and chronic myelocytic leukemia in blastic crisis (1.30 +/- 1.35 ng/ml) were not significantly elevated, but some of them showed an elevation of plasma u-PA. Plasma u-PA values were correlated with some of the fibrinolytic parameters such as FDP and D-dimer. Plasma u-PA antigen was decreased after the administration of antileukemic drugs in patients with APL. These results suggest that the coagulopathy in patients with various leukemias may in part be associated with u-PA release from the leukemic cells, especially in patients with APL. PMID- 7874009 TI - Low expression of the deoxycytidine kinase (dCK) gene in a 1-beta-D arabinofuranosylcytosine-resistant human leukemic cell line KY-Ra. AB - Molecular change of the deoxycytidine kinase (dCK) gene in a 1-beta-D arabinofuranosylcytosine-resistant human leukemic cell line (KY-Ra) was investigated. KY-Ra showed the same restriction pattern of genomic DNA and the same nucleotide sequences of the dCK gene as the parental cell line. However, the amount of deoxycytidine kinase mRNA was markedly decreased in KY-Ra compared to the parental cell line. This is the first report showing that the down regulation of dCK gene expression may be affected by a different mechanism than mutation. PMID- 7874010 TI - Fulminant bilateral cerebellar syndrome in a patient with chronic lymphocytic leukemia. AB - A 55 year old patient with chronic lymphocytic leukemia (CLL) and long-standing excessive lymphocytosis developed a rapidly progressive neurological syndrome. Differential diagnosis focused on two rate neurological complications in this disease: direct brain infiltration by leukemic cells versus progressive multifocal leukoencephalopathy (PML). Tissue diagnosis was not available. Two cerebro-spinal fluid examinations performed during the presence of the acute neurological symptoms were normal. Computed tomography (CT) showed low density lesions without enhancement and no mass effect within the left cerebellum. Magnetic resonance imaging scan (MRI) demonstrated multiple hyperintense areas in the brain stem, right and left cerebellum and right capsula interna, suggestive of demyelinative process. In our opinion these findings were compatible with the diagnosis of PML, but biopsy was not performed. Because of the different therapeutic approach in these two conditions, we feel that tissue diagnosis is warranted in patients with CLL who develop a rapidly progressive central nervous system complication in the presence of normal CSF. PMID- 7874011 TI - [VNK--a new gene for nonreceptor protein-tyrosine kinase, expressed in the murine brain and hematopoietic system]. PMID- 7874012 TI - [The effect of ultrasound on regeneration of skeletal muscles and status of the thymus gland in locally irradiated animals]. PMID- 7874013 TI - [Detection of extrahypothalamic nonapeptidergic neurosecretory cells in the rat brain]. PMID- 7874014 TI - [Neuroleptic catalepsy in rats is accompanied by activation of brain prolyl endopeptidase and is eliminated by inhibitors of this enzyme]. PMID- 7874015 TI - [The nature of specificity of integrating the IS50 element in Escherichia coli]. PMID- 7874016 TI - Significance of studies of the avian brain from three perspectives. AB - The avian brain has been one of the most popular subjects in neuroscience. Recent developments and findings related to avian studies from three different fields are described and their significance is discussed. These topics are: 1) paleontological discoveries indicating that birds are the successors of dinosaurs; 2) neuroanatomical findings indicating that there is a general pattern of information processing in the avian brain; and 3) an evolution hypothesis suggesting that the avian brain has neurons corresponding to those of the mammalian neocortex. PMID- 7874017 TI - Spontaneous urinary visible luminescence: characteristics and modification by oxidative stress-related clinical conditions. AB - Urinary visible luminescence is the result of the excretion of oxidized biomolecules and, as such, could provide a valuable index of systemic oxidative stress. The characteristics of the urinary luminescence that support this proposal are reviewed and the data obtained for patients with hyperthyroidism and children with Duchenne muscular dystrophy are also discussed. Enhanced urinary chemiluminescence was observed in both pathologies. A similar enhancement was obtained when the urinary luminescence of smokers was compared to that of non smokers. The possibilities and limitations of this noninvasive methodology for the evaluation of systemic oxidative stress is critically evaluated. PMID- 7874018 TI - Nylon-6 cylinders and a sponge-like derivative as supports for immobilizing trypsin. AB - 1. Two types of nylon-6 supports (small cylinders and a sponge-like derivative) were prepared for immobilizing enzymes. Nylon-6 beads were solubilized by immersion in 80% formic acid and then reprecipitated using two different types of non-solvent solutions (distilled water or a 1:1 acetone:water solution) giving rise to a sponge-like derivative and to a colloidal suspension, respectively. The latter was molded into a thin thread which was cut into small cylinders. 2. Trypsin (EC 3.4.21.4) was covalently bound to glutaraldehyde-activated nylon-6 cylinders as well as to the sponge-like derivative. The maximum (100%) apparent initial enzymatic activity was found for the trypsin bound to small cylinders, while the initial activity of trypsin bound to the sponge-like material was 61% in comparison with that of trypsin-small cylinders, under the same conditions of enzyme immobilization reaction (1 g of nylon support and 5 ml of 1.3 mg/ml trypsin in 0.1 M sodium phosphate buffer, pH 8.5, at 10 degrees C for 18 h) and of enzymatic reaction (1 g of trypsin-nylon in a batch reactor, 2 ml of 0.7% w/v azocasein solution in 50 mM borate buffer, pH 8.5, at 37 degrees C, with shaking, for 1 h). However, the decrease of activity after enzyme immobilization was more conspicuous for the trypsin-small cylinders than for the trypsin-sponge. The former retained approximately 25% of its initial activity, while the latter retained approximately 67% of its initial activity, after seven cycles of utilization for 1 h, pH 8.5, at 37 degrees C and 8 days of storage, pH 8.5, at 4 degrees C in the presence of azocasein. 3. Scanning electron microscopy was performed to visualize the surface of the support after each step of the immobilization process. The electron micrographs show that the two types of nylon supports had a rough surface, which became rougher and full of craters after treatment with 5 N HCl. On the other hand, the partially hydrolyzed nylon surface acquired the appearance of Swiss cheese after treatment with 2.5% glutaraldehyde. After reaction with the enzyme molecules the surface became rougher again. PMID- 7874019 TI - Mutagenic and genotoxic effects of mate (Ilex paraguariensis) in prokaryotic organisms. AB - 1. The mutagenic and genotoxic effects of mate (Ilex paraguariensis) aqueous solutions were analyzed in bacterial cells. 2. Mate solutions showed mutagenic activity in the Ames test (TA97, TA98, TA100 and TA102 strains) at concentrations of 20 to 50 mg/plate (mutagenic factors of 3.5 to 5.6) and genotoxic activity in the inductest (WP2s (lambda) strain), with a maximal phage induction at concentrations of 10 to 20 mg/plate. Above these concentrations the mate solutions were cytotoxic. 3. Addition of 5 U/ml catalase, 20 microliters/ml S9 rat liver microsomal fraction, 100 mM thiourea or 10 mM dipyridyl completely inhibited the lysogenic induction produced by mate; however, the addition of 1,000 U/ml superoxide dismutase was almost ineffective. 4. Oxygen reactive species may be present in mate solutions playing an essential role in its genotoxicity. PMID- 7874020 TI - Iron uptake from lactoferrin by intestinal brush-border membrane vesicles of human neonates. AB - It is uncertain to what extent the binding of human lactoferrin (LF) to its receptor in the intestinal brush-border membrane affects iron uptake in infants. The purpose of this study was to investigate iron uptake from human LF by brush border membrane vesicles (BBMV) obtained from the small intestine of human neonates. LF was purified from pooled human colostrum. Uptake experiments were performed by incubation of 55Fe-citrate or 55Fe-LF with BBMV, followed by rapid filtration through microporous filters. 55Fe uptake from LF by BBMV was dependent on pH, with a maximum at 7.5, and increased with incubation time, reaching a maximum at 1 min. When 55Fe was bound to citrate, uptake was slower (maximum at 5 min) and not dependent on pH. In both experiments, the maximum uptake of iron bound to LF was about twice that of iron bound to citrate (230 pmol and 105 pmol/mg microvillus protein, respectively). Partial degradation of LF in two fragments resulted in the loss of its capacity to increase iron uptake by BBMV. From these preliminary results we conclude that LF may increase iron absorption during the neonatal period, contributing to the high bioavailability of this mineral in human milk. PMID- 7874021 TI - Role of the microtubular system in platelet aggregation. AB - 1. Four structural systems are involved in the process of platelet activation that leads to aggregation: 1) the membrane system, i.e., the cytoplasmic membrane, the dense tubular structure and the open canalicular structure; 2) alpha and dense granules; 3) the peripheral microtubular coils; 4) the microfibrillar meshwork of actin-myosin bundles. 2. We added four compounds which modify cell ultrastructure to normal platelet-rich plasma to analyze the behavior of the structural systems of platelet activation: vinblastine (100 micrograms/ml) and cimetidine (100 micrograms/ml) that act on the membrane system, ticlopidine (200 micrograms/ml) and colchicine (100 micrograms/ml) that affect primarily the microtubular structure, cytochalasin B (30 micrograms/ml) and phorbol myristate acetate (100 ng/ml) that act upon the granular system, and cytochalasin D (30 micrograms/ml) and concanavalin A (50 micrograms/ml) that influence the microfibrillar structure. Platelet aggregation was stimulated by epinephrine or thrombin. 3. Cimetidine and ticlopidine prevented aggregation. However, neither substance affected the microtubular structure. Colchicine and cytochalasin B only partially impaired aggregation, because pieces of microtubules remained in the presence of these substances. The other substances did not present anti-aggregant activity and did not preserve the microtubules. 4. We infer that the disappearance of the microtubules is necessary to produce aggregation. When they remain intact no aggregation is produced, even though the other structural systems are activated. PMID- 7874022 TI - Fecal loss and clearance of alpha-1-antitrypsin in children with persistent diarrhea. AB - 1. Daily fecal loss and daily clearance of alpha-1-antitrypsin were determined in 30 infants without intestinal disorders and in 21 with persistent diarrhea. 2. Stools were collected during a 48-h period and a randomly obtained single sample was also collected. Blood samples were also collected from the infants, and alpha 1-antitrypsin was measured by radial immunodiffusion in both stool and serum. 3. No difference in daily fecal loss (mg/d) of alpha-1-antitrypsin was detected between the control group and the group with persistent diarrhea (11 +/- 9.3 vs 18.5 +/- 20 mg/d). No difference in daily alpha-1-antitrypsin clearance (ml/d) was detected between the control group and the group with persistent diarrhea (4.3 +/- 3.6 vs 5.2 +/- 4.8 ml/d). 4. There was a strong correlation between daily fecal loss and daily clearance of alpha-1-antitrypsin (N = 50). There was a weak correlation between the concentrations of alpha-1-antitrypsin in randomly obtained single samples and daily fecal loss of the antiprotease (N = 25; r = 0.183; P < 0.01). 5. We conclude that: a) there is no increased fecal loss of alpha-1-antitrypsin persistent in diarrhea; b) fecal alpha-1-antitrypsin clearance is not necessary to estimate the enteric loss of the antiprotease; c) the determination of alpha-1-antitrypsin in random samples of feces is not a reliable method. PMID- 7874023 TI - Radioaerosol 99mTc-DTPA characterization produced by some nebulizers. AB - 1. The radioaerosol 99mTc-DTPA produced by jet and ultrasonic nebulizers was characterized by measuring the median mass diameter (MMD) and geometric standard deviation (sigma g) and these characteristics were interpreted in terms of the aerodynamic principles of inertial impactation. 2. Jet nebulizers of the same model, with different outflows (NSA = 0.14 ml/min; NSB = 0.24 ml/min and NSC = 0.40 ml/min) showed different radioaerosol mass distribution, with MMD (NSC) > MMD (NSA). The ultrasonic nebulizer US-1000 from Narcosul, which is operated with an air flow of 2 l/min and frequency of 1.6 MHz, generated radioaerosol with MMD = 2.40 microns, higher than that obtained with most of the jet nebulizers evaluated (NSA = 1.50 microns; NSB1V = 1.40 microns; NSB2V = 1.20 microns and PITT#1 - 0.80 microns), and the ultrasonic nebulizer presented the highest outflow of the nebulized solution (1.15 ml/min). 3. Connecting one or two impactation reservoirs to the NSB jet nebulizer modified the mass distribution, which became significantly narrower for NSB2V when compared to the other two nebulizers. NSB2V presented a mass percentage with a diameter of 3 microns or less and a sufficient outflow for use in ventilation and pulmonary permeability studies. 4. Comparison of the mass collected in the cascade impactor and the total mass generated by the NSB, NSB1V and NSB2V nebulizers showed, on average, 4.5% efficiency in radioaerosol generation with a diameter of less than 16 microns and 3.2% efficiency for a diameter of 3 microns or less. PMID- 7874024 TI - Studies on the efficiency of measles virus antigen production using VERO cell culture in a microcarrier system. AB - 1. A large amount of antigen is required to conduct seroepidemiologic surveys of measles. Thus, a process to obtain measles virus antigen using a bioreactor was standardized. 2. The virus was grown in a 3.7-1 culture of VERO cells using a Celligen cell culture system containing 2 mg/ml of microcarriers (cytodex I) at 37 degrees C and 60 rpm. The cultures infected with 0.5 m.o.i. of measles virus were harvested after the appearance of the cytopathic effect. The virus suspension was clarified and concentrated by ultracentrifugation. Intracellular and extracellular virus titers were determined by hemagglutination (HA) and by induction of a cytopathic effect in cell culture (TCID50). 3. Intracellular virus presented 5-7 x 10(6) TCID50/0.1 ml, HA activity per 50 microliters equal to 32, with a total HA activity of 4,480 HA units (HAU) and specific activity of 116 HAU/mg. In the concentrated supernatants, the HA titer of extracellular virus was 64, with a total HA activity of 1,024 HAU and a specific activity of 1,600 HAU/mg. 4. The antigen obtained was suitable for the detection of antibodies against measles virus in assays such as ELISA and DOT-ELISA (using 1 micrograms/well to ELISA and 2 micrograms/DOT). 5. The microcarrier system produced antigen sufficient for 26 ELISAs/ml compared to 5.7 ELISAs/ml obtained for the static culture system. PMID- 7874025 TI - Effects of temperature on leucocytes of Colossoma macropomum and Hoplosternum littorale (Pisces). AB - 1. The effects of different thermal regimens on qualitative and quantitative characteristics of leucocytes were evaluated in two fish species of the Amazon region. 2. The proportion of circulating types of leucocytes changed significantly in Colossoma macropomum (tambaqui) but not in Hoplosternum littorale (tamoata) exposed for four-week terms to 20, 25, 30, 35, and 40 degrees C. 3. The proportion of circulating lymphocytes decreased significantly in tambaquis exposed to 30, 35, and 40 degrees C. No changes in lymphocyte proportions were observed in tamoatas. 4. Neutrophils were almost absent in tambaquis, except in animals exposed to 40 degrees C. No significant changes in circulating neutrophils were observed in tamoatas. 5. The circulating leucocytes of Colossoma macropomum and Hoplosternum littorale are affected in different ways by temperature changes, suggesting species-specific adjustments to this parameter. PMID- 7874026 TI - Relationship between apoptosis and thymocyte depletion in rabies-infected mice. AB - The apoptosis of thymocytes from rabies-infected mice was investigated in a kinetic study covering the entire course of the infection. For this study, BALB/c mice (6-7-week old females) were inoculated intracerebrally with 100 LD50 of Challenge Virus Strain, a fixed rabies virus strain, and three animals were sacrificed per time point to remove thymuses. When thymocytes were fixed, stained with propidium iodide and analyzed by flow cytometry, a distinct subpopulation of cells was observed below the G0/G1 region, denoted as the A0 region. Cells in this region presented reduced fluorescence, and nuclear DNA fragmentation. The accumulation of cells in the A0 region, after infection, progressively increased, reaching 12% for unfractionated thymocytes, 62% for thymocytes from the 60% Percoll interface and 32% for thymocytes recovered at the 100% Percoll interface. This finding, observed only in thymocytes from infected mice, demonstrates a clear modification of chromatin condensation in these cells, suggesting the occurrence of an apoptotic process during rabies infection. PMID- 7874027 TI - Increase of B-lymphocyte number and activity during experimental murine schistosomiasis mansoni. AB - 1. In schistosomal infection, the hyperergic acute phase of the disease evolves progressively into the chronic one, with establishment of a relative equilibrium between the parasites and the corresponding host responses. This down-regulation of host reactivity is considered to be under the control of T-lymphocyte circuits. 2. In the present study, we investigated lymphocyte populations in spleens of normal mice and the kinetics of the B-cell number increase in mice in the acute, chronic and late chronic phases of schistosomal infection, and we monitored their proliferation and activity in antibody isotype secretion. 3. We observed polyclonal B-cell activation and modulation of Ig isotype production, compatible with the alternate predominance of TH2 and TH1 lymphocyte subsets, in the acute and the chronic phases of the disease, respectively. PMID- 7874028 TI - The absence of gamma-interferon production of S. mansoni antigens in patients with schistosomiasis. AB - No gamma-interferon production was observed in peripheral blood mononuclear cells (PBMC) cultures from 45 patients living in an endemic area of schistosomiasis in Brazil following in vitro stimulation with schistosomula or adult worm antigens from Schistosoma mansoni (4.9 +/- 24 and 1.0 +/- 3.4 pg/ml, respectively). This immunological abnormality was observed in patients both with a high degree of infection (> or = 400 eggs/g feces) and with a low degree of infection (< 400 eggs/g feces), and was independent of the degree of natural exposure to infection. This absence of gamma-interferon production was antigen specific since high levels of this cytokine were detected in the same patients when their cells were stimulated with PPD (247 +/- 179 pg/ml) or PHA (408 +/- 328 pg/ml). In two of four subjects cured of a previous S. mansoni infection and currently living outside the endemic area, gamma-IFN was produced when their PBMC were stimulated with adult worm antigen (75 +/- 2.5 pg/ml). PMID- 7874029 TI - Production and immunochemical characterization of Neisseria meningitidis group B antiserum for the diagnosis of purulent meningitis. AB - Unlike Neisseria meningitidis groups A, C, Y and W135, the group B capsular polysaccharide has been shown to be chemically and immunologically identical to the capsular polysaccharide of Escherichia coli K1. Both components are sialic acid homopolymers and are poorly immunogenic. Nevertheless, due to the high incidence of Neisseria meningitidis group B meningitis in the population of the State of Sao Paulo, preparing antiserum to this serogroup for diagnostic purposes has become a matter of high priority. Of the many immunization schemes proposed, intravenous inoculation of whole bacteria previously inactivated with formaldehyde and simultaneous intradermal inoculation with a mixture of the bacterial polysaccharide fraction and whole bacteria in complete Freund;s adjuvant have produced the best results. The antiserum was treated with immunoadsorbents prepared with aluminum chloride and protein and/or polysaccharide antigens from each of the following heterologous bacteria: Haemophilus influenzae type b, Streptococcus pneumoniae, Escherichia coli other than K1, and Staphylococcus aureus, in order to eliminate cross-reactivity. For quality control analysis, the antiserum was assessed by the immunodiffusion, counterimmunoelectrophoresis, dot-ELISA, and immuno-blot techniques against homologous antigens. Specificity was obtained after treating the antiserum with Haemophilus influenzae type b polysaccharide immunosorbent. PMID- 7874030 TI - Increased serotonin levels in physically trained men. AB - It has been postulated that exercise training influences monoaminergic systems. The purpose of the present study was to determine the basal level of serum serotonin (5HT) in track and field-trained men (N = 15) and in untrained subjects matched by age, weight and height (N = 15). Serum serotonin levels were determined in blood drawn into dry tubes after a 12-h fast by high performance liquid chromatography utilizing electrochemical detection. Mean (+/- SD) serum serotonin levels were: 141.32 +/- 38.77 ng/ml for trained subjects and 97.77 +/- 30.53 ng/ml for untrained subjects (P < 0.01, Student t-test). These data show that basal serum serotonin levels are increased by exercise training. PMID- 7874031 TI - Apoptosis in the developing retina: paradoxical effects of protein synthesis inhibition. AB - Cell death by apoptosis is usually characterized as an active process that requires protein and RNA synthesis. The requirement of protein synthesis for the degeneration of ganglion cells and other cell types was studied in neural retinae explanted from the eyes of newborn rats. Ganglion cells were detected by the presence of retrogradely transported horseradish peroxidase injected into the superior colliculus. Apoptotic cells were recognized by their condensed and deeply stained chromatin. The data show that the death of ganglion cells, whose axons are damaged when preparing the explants, is blocked or delayed by protein synthesis inhibitors. In contrast, the blockade of protein synthesis produced cell death with apoptotic morphology in the neuroblastic layer of the same retinae. The results suggest the operation in the developing retina of both a program of apoptosis dependent on the synthesis of killer proteins, and a latent mechanism of apoptosis that is normally blocked by repressor proteins. PMID- 7874032 TI - Emergence of T-lymphocytes, eosinophils and dendritic cells in the bronchi of actively sensitized guinea pigs after antigenic challenge. AB - Bronchi from guinea pigs actively sensitized to ovalbumin and boosted two weeks later display increased numbers of CD4+ T-lymphocytes and eosinophils. We have further investigated immunopathological changes in sensitized guinea pigs 2 or 24 h after antigenic challenge with ovalbumin. Lungs were resected, frozen and cryostat sections stained with monoclonal antibodies that recognize relevant guinea pig epitopes. Cyanide-resistant peroxidase activity was used to stain eosinophils. No further increase in T-lymphocytes or eosinophils was observed 2 h after challenge. At 24 h, a marked increase in EPO+ eosinophils was found, and this was accompanied by severe mucosal damage characterized by epithelial shedding and ulceration. The numbers of T-lymphocytes remained stable but a novel population of cells with the appearance of dendritic cells was seen in the bronchial wall. They were negative for macrophage markers but were strongly Class II positive. These findings suggest that antigenic challenge results in further recruitment of eosinophils, their activation and release of toxic substances to the epithelium. Furthermore, other cell types, possibly dendritic cells, are attracted to the bronchi and could play a role in maintaining allergic inflammation via antigen presentation. PMID- 7874033 TI - Normative Speaking Fundamental Frequency (SFF) characteristics of Brazilian male subjects. AB - The present study was carried out in order to obtain normative Speaking Fundamental Frequency (SFF) data for 150 Brazilian Portuguese-speaking male subjects (mean age, 19.4; range, 17-30) in two different vocal tasks, i.e., oral reading and counting. Mean (+/- SD) SFF was 134.9 +/- 17.9 Hz for oral reading and 130.5 +/- 18.5 Hz for counting. The mean SFF values obtained in this investigation were similar to data reported in previous studies. PMID- 7874034 TI - Relationship between plasma 17-beta estradiol on the day of estrus and number of viable embryos in Bos indicus (Nellore) cows superovulated with FSH. AB - Thirteen cows, Bos indicus, of the Nellore breed were superovulated with 22 mg of follicle stimulating hormone (FSH) administered by intramuscular route during four consecutive days (D10, D11, D12 and D13), starting on the 10th day of the estrous cycle (day 0 = estrus). Prostaglandin (PGF2 alpha, 1.0 mg, im) was administered on D12, 48 h after the first FSH injection, for the induction of estrus on D14, when artificial insemination was performed. Seven days later (D21 of the cycle), embryos were collected, and evaluated, and the ovarian response was estimated on the basis of number of corpora lutea determined by rectal palpation. Blood samples were obtained for the determination of plasma 17-beta estradiol on D10, D11, D12, D13, D14 and D21 and plasma progesterone on D14 by RIA. The donors were divided into two groups according to progesterone levels on D14, the day of the induced estrus (GI: P4 < or = 1.00 ng/ml, N = 5 and GII: P4 > 1.00 ng/ml, N = 8). A linear positive correlation was observed between plasma 17 beta estradiol concentration on the day of estrus and viable embryo number. We conclude that plasma 17-beta estradiol and progesterone concentrations on the day of estrus can be used to predict the viability of embryos recovered from Nellore cows superovulated with FSH. PMID- 7874036 TI - Staff behaviour and its implications for people with learning disabilities and challenging behaviours. AB - Many people with learning disabilities engage in challenging behaviours which, behaviour analytic models suggest, are social behaviours sensitive to the actions of others in the environment. In this paper, the research literature on the behaviour of staff, especially that pertaining to interactions with people with challenging behaviours, is reviewed. Empirical evidence is found to support the hypothesis that staff actions affect clients' challenging behaviours. In addition, studies of staff behaviour show that their behaviour is often counter habilitative. Firstly, staff spend little time interacting with clients and the quality of these interactions is often poor. Secondly, observational studies have shown that staff respond intermittently to challenging behaviours, and self report studies indicate that many of these responses are of a nature that may reinforce such behaviours. Finally, although limited, evidence suggests that behavioural programmes for clients with challenging behaviours are rare and where they do exist they are often not carried out by staff. To date, interventions for staff behaviour (training and management approaches) have acted to change these ways of behaving but have not been founded on adequate analyses of staff action. A call is made for analyses of staff behaviour, and other implications for research and practical work with staff are discussed. PMID- 7874035 TI - Sex-related differences in the analgesic response to the rat tail immersion test. AB - The analgesic response was evaluated by the tail immersion test in adult male (N = 30), female (N = 21) and androgenized female Wistar rats (N = 15). The reaction time for tail withdrawal from the hot water bath was faster for male than for female rats (3.48 +/- 0.12 vs 6.46 +/- 0.42 s). The reaction time of androgenized female rats was similar to that of male rats (3.08 +/- 0.16 s). Blockade of opiate receptors with naloxone (2 mg/kg, ip) decreased the sensitivity to the noxious stimuli in males (4.08 +/- 0.10 s) and in androgenized females (3.69 +/- 0.19 s) but increased it in female rats (5.01 +/- 0.41 s). These data show sex related differences in the analgesic response evaluated by the tail immersion test and indicate that administration of androgens to newborn female rats affects their pain sensitivity. PMID- 7874037 TI - Epistemology and learning disabilities: invited commentary on Hastings and Remington. AB - The effect on service provision of describing a variety of actions as challenging behaviour is discussed: it is suggested that studying stereotyped, aggressive and self-injurious acts in their own right has yielded more useful psychological debate, and ignoring such conceptual thinking leads to implicit theorizing where assumptions go unquestioned. Evidence for the relevance of staff actions on different topographies of client responses is critically reviewed, alongside discussion of the authors' rhetoric. The importance of adjusting language and frameworks to make room for alternative conceptualizations is discussed. The article concludes by recommending that research into staff attitudes and actions will be better served by reflexive methods and reporting which emphasize mutuality. PMID- 7874038 TI - Quality assurance in mental health: the QUARTZ system. AB - This paper is concerned with how quality might be assured in mental health services. It includes an account of why a concern with quality and quality assurance procedures are now high on the agenda of the Health Service. A quality assurance programme requires a decision about what elements of a service to monitor, what information is relevant, how it can be collected, and a system for acting on the results. This paper provides a brief review of the kind of information that has been considered relevant and the methods that have been used to collect it. In addition, the principles underlying good and comprehensive quality assurance programmes will be outlined and the development of a particular system, known as QUARTZ, which has attempted to incorporate these principles, described briefly. PMID- 7874039 TI - Sequences of emotional distress expressed by clients and acknowledged by therapists: are they associated more with some therapists than others? AB - When clients come to psychotherapy they are distressed, this distress usually being expressed in the form of anxiety, hostility, depression and helplessness. This study explored the sequences of emotional distress expressed by clients and acknowledged by therapists, and examined their associations with other factors. The transcripts of five therapists (two single sessions each) were content analysed: they used personal construct, client centered, rational-emotive, Gestalt and transactional analysis therapy. Log-linear analyses of appropriate contingency table cell frequencies were conducted to test associations between identified sequences and the two variables of therapist and timing of completion of the sequence. Therapist-client sequences of Anxiety-Anxiety, Anxiety-Hostility and Helplessness-Hostility were found to be associated more with the personal construct and client centred therapists than with the rational-emotive therapist. Client-therapist sequences of Anxiety-Anxiety, Helplessness-Anxiety and Helplessness-Helplessness were more often found with the client centred therapist than the other therapists. For most of these sequences timing had an effect, yet timing rarely interacted with the therapist variable. The findings are discussed in terms of their relevance to the theoretical positions represented, the shortcomings of the research and the value of this methodology in studies linking therapy process with outcome. PMID- 7874040 TI - Identification of subtypes of problem drinkers based on neuropsychological performance. AB - The key issue addressed in this paper is: Can specific subtypes of drinkers be identified on the basis of their neuropsychological performance? A multivariate model of neuropsychological deficits related to alcohol abuse was proposed and cluster analysis was used to see if subtypes could be identified which matched those indicated in the multivariate model. A neuropsychological cognitive assessment battery was given to a wide variety of drinkers (N = 88). Factor analysis yielded scores on four factors which formed the basis for the cluster analysis. Seven stable clusters were identified based on cognitive performance alone. Additionally, clusters were significantly differentiated by age, IQ, education, number of units of alcohol consumed on a heavy drinking day, nutritional status, stress and the Eysenck Personality Questionnaire Lie score. The seven clusters were eventually profiled as healthy males, healthy females, males with stress-related deficits, females with stress-related deficits, mildly impaired males, deficits related to liver dysfunction and mild alcoholic Korsakoff syndrome. The clusters successfully mapped onto the proposed model reinforcing the need for a multivariate approach to the study of neuropsychological deficits in problem drinkers. PMID- 7874041 TI - Habituation patterns to colour naming of eating-related stimuli in anorexics and non-clinical controls. AB - The current study was an investigation into intra-session changes in the pattern of Stroop colour-naming impairments with body shape-related words and food related words. The subject pool comprised anorexic women and a control group of non-clinically disordered women. The results indicated that anorexic women show greater colour-naming decrements that non-disordered controls for both types of eating-related words. Stroop interference significantly decreased across the course of the experiment with the body-shape words for the anorexic subjects, thereby indicating habituation to the semantic content of those words. There was no comparable process of habituation observed with the food-related words. PMID- 7874042 TI - Detection of acquired deficits in general intelligence using the National Adult Reading Test and Raven's Standard Progressive Matrices. AB - A multiple regression equation for estimating premorbid Raven's Standard Progressive Matrices (RSPM) scores on the basis of age and the National Adult Reading Test (NART) was derived. A sample of patients with confirmed cerebral lesions was examined to determine the proportion of patients with significant discrepancies between their predicted and obtained RSPM performance. The sensitivity of the procedure was modest (52 per cent), although a comparison with discrepancies between premorbid and current performance on the Wechsler scales indicated that the RSPM was more sensitive to neuropathology. These findings suggest that when NART-intelligence test comparisons are used to diagnose cerebral impairment, the likelihood of a false-negative diagnosis is high. PMID- 7874043 TI - Movement, face processing and schizophrenia: evidence of a differential deficit in expression analysis. AB - Three dynamic face-processing tasks based on the Bruce & Young (1986) functional model of face processing were presented to 10 schizophrenic and 10 depressed inpatients and to 10 non-patient subjects. Familiar face recognition, facial expression recognition and unfamiliar face matching were examined. Schizophrenic patients' performance was significantly poorer than that of depressed patients and non-patient controls. Significantly lower scores were obtained on the facial expression recognition task than on the familiar face recognition task. There was a differential pattern of group performance on each of the three tasks: schizophrenic and depressed patients were as accurate as non-patient controls on the familiar face recognition task, but significantly less accurate than non patient controls on the unfamiliar face-matching task. Schizophrenic patients were significantly less accurate than depressed patients and non-patient controls on the facial expression recognition task. The results are contrasted with an analogous static face-processing study. PMID- 7874044 TI - A study of two dementia quizzes. AB - A dementia quiz was developed to assess carers' and professionals' knowledge about dementia, services needed by dementia sufferers and their families, and methods of coping with some of the problems presented by people with dementia. The quiz was compared with a UK version of Dieckmann, Zarit, Zarit & Gatz's (1988) Alzheimer's Disease Knowledge Test, one of only two published tests assessing knowledge about dementia. Both measures were given to samples of carers and professionals who were either members or non-members of Alzheimer's Disease Society. The responses were analysed to determine the reliability and validity of the new Dementia Quiz. The results were encouraging and the quiz should prove useful in teaching, clinical and research settings. PMID- 7874045 TI - Chronic pain and attention: a cognitive approach. AB - The present study draws upon resource-based models of attention in suggesting that the processing of chronic and persistent pain is a task that demands the application of central and executive attention. If a chronic and persistent pain stimulus is demanding of central, attentional resources, it follows that it will compete with a second attention-demanding task for those limited resources. Here it is hypothesized that performance of an attention-demanding interference task will be detrimentally affected by the demands of persistent pain. In Expt 1, patients in high pain, patients in low pain and control subjects without pain performed an attention-demanding numerical interference task. There were no significant differences between any of the groups on any measure of performance. Expt 2 repeated Expt 1 with a more difficult and more complex task. Only when the task was at its most difficult and its most complex (i.e. at the greatest demand of limited resources) did those patients in high levels of pain (i.e. at the greatest demand of limited resources) show performance decrements. The results of both experiments are discussed in relation to the debate concerning the use of cognitive methods for pain control and in relation to the application of cognitive psychology to the study of chronic pain. PMID- 7874046 TI - The dentist's attitudes and their interaction with patient involvement in oral hygiene compliance. AB - The influence on patient compliance of the dentist's attitudes to his or her job and to his or her patient was studied in a sample of 82 patients. The dentist's attitudes were assessed at the beginning of dental treatment. Treatment consisted of cleaning, depuration and motivation. At follow-up examination after six months, attendance at follow-up and the development of plaque, calculus and gingivitis were significantly predicted by the dentist's attitudes. A causal model, which also included factors of patient involvement, was developed. The compliance-producing factors were, primarily, the establishment of sympathy and an informal relationship between dentist and patient. The patient's habit of regularly making visits to a dentist, in a complex way, also contributed to compliance. PMID- 7874048 TI - Effectiveness of training to prevent job-related back pain: a meta-analysis. AB - Data from a meta-analysis, involving six experimental studies, revealed a modest relationship between training of employees and a decrease in the occurrence of back pain or sick leave associated with this disorder. The implications for prevention of job-related back pain, and future research within this field are discussed. PMID- 7874047 TI - The effects of minor events, optimism and self-esteem on health. AB - Recent research shows upper respiratory infections (URIs) are influenced by minor daily events, especially those that are desirable and interpersonal in nature. The present study used a longer time frame, broader health measures and a between subjects design to examine this effect. It also predicted that optimism and self esteem would interact with minor events to affect health. One hundred and fifty participants provided information regarding minor events, disposition and physical health on two separate occasions. Results show that increases in both desirable and undesirable events (hassles and uplifts) affected URIs over a two week period. Interpersonal hassles interacted with optimism, having a greater impact on physical symptoms for optimists than for pessimists. Self-esteem did not interact with minor events to affect health. These results extend previous findings to show that minor events affect URIs and not other health outcomes, and that this effect is apparent between subjects over a number of days. Further, the influence of interpersonal events on health appears to be moderated by optimism. It is concluded that consideration and integration of findings from studies with different methodologies will be beneficial in furthering our understanding of minor event effects on health. PMID- 7874049 TI - Stress, arousal, cortisol and secretory immunoglobulin A in students undergoing assessment. AB - Cortisol, salivary immunoglobulin A, stress and arousal reports were measured in students undergoing academic assessment. In accordance with hypotheses, all measures were higher on the day of assessment than a week before, and were highest of all immediately after assessment. PMID- 7874050 TI - Development of a thermoelectric cooling apparatus for high-voltage isoelectric focusing on a cellulose acetate membrane. AB - To develop an isoelectric focusing apparatus using a cellulose acetate membrane (Separax EF), we have designed a thermoelectric cooling isoelectric apparatus. This apparatus has two characteristics. Firstly, the cooling system was switched to a thermoelectric cooling system from an ice-cooling system. Secondly, the chamber lid of the electrophoretic apparatus was also devised so that samples could be applied without opening the chamber lid. With this apparatus we could perform the isoelectric focusing without worrying about room temperature and humidity in the laboratory. Applying 2000 V for an extra 5 min with our module cooling system, we achieved a much higher degree of resolution with three sheets of cellulose acetate membrane (Separax EF) overlaid for simultaneous electrophoresis. Thus, three types of information could be obtained from only one electrophoretic procedure. PMID- 7874051 TI - Sulfation of parabens and tyrosylpeptides by bacterial arylsulfate sulfotransferases. AB - Arylsulfate sulfotransferase purified from Eubacterium A-44 has higher specific activity than the enzymes from Klebsiella K-36 and Haemophilus K-12. Propylparaben and butylparaben were good substrates among several parabens. The antibacterial activity of parabens was reduced by the sulfation of the phenolic hydroxy group. Tyrosine-containing peptides, kyotorphin, enkephalin and cholecystokinin non-sulfate, were effective as acceptor substrates by A-44, K-36 and K-12 sulfotransferases. PMID- 7874052 TI - Inhibition of Helicobacter pylori urease activity by hydroxamic acid derivatives. AB - Helicobacter pylori (HP) produces strong urease [EC 3.5.1.5], which is considered to play a role in the pathogenesis of gastritis and peptic ulcers. Inhibitions against this enzyme have been studied with hydroxamic acid (HXA) derivatives of aliphatic or aromatic carboxylic acids, amino acids and dipeptides. A number of HXAs potently inhibited the urease (I50 values were near the order of 10(-6)M), and H-Ile-Gly-NHOH (I50 = 0.20 x 10(-6)M) was the most potent inhibitor among the derivatives. HP urease was inhibited more potently, in general, than Jack bean (JB) urease by HXAs, and a correlation between the chemical structures of HXA derivatives and their inhibitory effects on HP urease was observed, in comparison with JB urease. PMID- 7874053 TI - Secretion of intrinsic factor from cultured rat gastric chief cells. AB - Intrinsic factor (IF) is a vitamin B12 binding protein that is secreted from the gastric mucosa. We tested secretagogues which stimulate IF secretion in rat gastric perfusion and found that carbachol and cholecystokinin octapeptide (CCK 8) stimulated secretion, but histamine and tetragastrin did not. To confirm these results, we examined IF secretion from isolated rat chief cells. For this purpose, we established an enzyme immunoassay (EIA) using an avidin-biotin peroxidase complex to measure small amounts of IF. To prepare an anti-rat IF, IF was isolated from the stomach, and was injected into a rabbit for immunization. Rat gastric chief cells were isolated from the gastric mucosa with Dispase and a Percoll gradient centrifugation, and were cultured. We examined the effects of chemicals by adding them to culture dishes of chief cells in a CO2 incubator. Released IF in culture medium was determined by EIA. Carbachol, CCK-8 and secretin stimulated IF secretion from cultured chief cells, while histamine and tetragastrin did not; Forskolin and A23187 also stimulated the secretion. We concluded that carbachol and CCK-8 stimulated IF secretion via an increase of intracellular Ca2+ concentration and that secretin did so via a cAMP accumulation. PMID- 7874054 TI - Effects of DX-9386, a traditional Chinese medicinal prescription, on long-term potentiation in the dentate gyrus in rats. AB - DX-9386, a traditional Chinese medicinal prescription consisting of ginseng, polygala, acorus and hoelen in the ratio of 1:1:25:50 (dry weight), was studied regarding the formation of long-term potentiation (LTP) in the dentate gyrus of anesthetized rats. Single oral administration of DX-9386 did not affect LTP formation evoked by suprathreshold tetanic stimulation; however, it significantly intensified the spike amplitude evoked by a subthreshold stimulation. LTP formation induced by suprathreshold tetanus was significantly inhibited by ethanol given either orally or intracerebroventricularly. DX-9386 significantly antagonized this inhibitory effect of ethanol. Basal spike amplitude was not influenced by DX-9386. These results indicate that DX-9386 potentiated LTP formation in the hippocampus and suggest that the ameliorative effect of this prescription on learning deficit model animals was, at least partly, due to its direct action on the hippocampus. PMID- 7874055 TI - Effects of diazoxide on norepinephrine-induced vasocontraction and ischemic myocardium in rats. AB - Effects of diazoxide on norepinephrine-induced vasocontraction in vitro and global ischemia-induced lactate accumulation in the myocardial tissue in vivo were studied in rats. Diazoxide produced relaxation of the isolated rat aorta contracted by norepinephrine in a dose dependent manner. The relaxation of the aorta was associated with reduction of intracellular Ca2+ concentration. This reduction may be due either to activation of KATP channels or Na(+)-K+ ATPase, or to both. Global ischemia induced by aorta constriction for 30 min in vivo increased the myocardial tissue level of lactate. Pretreatment with diazoxide (10 mg.kg-1, i.v.) significantly attenuated the accumulation of lactate due to global ischemia. The present study suggests that diazoxide reduces ischemic influence on the myocardium partly through its vasodilatory action. PMID- 7874056 TI - Antinociceptive and antipyretic effects of alkaloids extracted from the stem bark of Hunteria zeylanica. AB - Effects of crude alkaloids extracted from the stem bark of Hunteria zeylanica Gard. (H. zeylanica) on nociceptive responses, capillary permeability, yeast induced hyperthermia, pentobarbital-induced sleep, and spontaneous motor activity were investigated. Oral administration of 50 mg/kg H. zeylanica alkaloid extract significantly decreased the number of writhings induced by intraperitoneal acetic acid. The extract at 100-200 mg/kg significantly increased nociceptive threshold of the inflamed but not the non-inflamed paw in the Randall-Selitto test. Moreover, in the formalin test, the extract (100 mg/kg) significantly decreased licking activity in the late phase without affecting the activity in the early phase. However, the extract did not produce antinociceptive effect in the hot plate test, while it inhibited increase of vascular permeability induced by acetic acid in the capillary permeability test. Moreover, the extract dose dependently reduced yeast-induced hyperthermia in rats without affecting normothermia. It did not affect pentobarbital-induced sleep, but significantly increased locomotor activity at 100 mg/kg. These results suggest that H. zeylanica alkaloid extract possesses antinociceptive and antipyretic effects, and that the former effect may be mediated by its anti-inflammatory action. PMID- 7874057 TI - Cytotoxicity of 1,3-dichloropropene and cellular phospholipid peroxidation in isolated rat hepatocytes, and its prevention by alpha-tocopherol. AB - 1,3-Dichloropropene induced time- and dose-dependent toxicity and lipid peroxidation were examined in isolated rat hepatocytes. HPLC method with chemiluminescence detection (CL-HPLC) was employed to determine phosphatidylcholine hydroperoxide (PCOOH) and phosphatidylethanolamine hydroperoxide (PEOOH) contents. The release of lactate dehydrogenase (LDH) as a toxicological parameter was significantly increased after 90 min incubation at 1 mM of 1,3-dichloropropene and after 60 min incubation at 5 mM, respectively. The cellular PCOOH and PEOOH contents were increased after 90 min incubation at 1 mM of 1,3-dichloropropene, and after 15 min for PCOOH and 30 min for PEOOH at 5 mM, respectively. The increase of cellular phospholipid hydroperoxide preceded the cytotoxicity. Hepatotoxicity was effectively prevented by preincubation with d,1 alpha-tocopherol (alpha-toc.) accompanied by prevention of the membrane phospholipid peroxidation. In conclusion, the peroxidation of phospholipid preceded cytotoxicity, and cytotoxicity was effectively prevented by alpha-toc. These results indicated that the peroxidative degradation of membrane phospholipid is one of the main causes of cytotoxicity by 1,3-dichloropropene. PMID- 7874058 TI - Urinary protein fractions in healthy subjects using cellulose acetate membrane electrophoresis followed by staining with acid violet 17. AB - We fractionated normal urinary proteins obtained from 40 healthy subjects using cellulose acetate membrane electrophoresis and stained them with Acid Violet 17. The electrophoretic patterns were classified into four groups. Each of groups I, II, III, IV had an albumin peak and 1, 2, 3, and 4 additional globulin peaks, respectively. Within-day variation study showed that the pattern was fundamentally specific to the individual, although some intermediate cases were observed. We were unable to determine which type was standard for normal subjects. However, the concentration of Tamm-Horsfall protein was speculated to be an important factor in determining the patterns. Group III showed significantly higher values than group I in urine albumin, total protein, and beta-N-acetyl-D-glucosaminidase and this group was believed to include subjects in the subclinical stage of a glomerular disease. All specimens belonging to group IV showed an obvious fraction of alpha 1 globulin which is often found in urine specimens of patients with renal diseases of tubular origin or other pathological conditions. PMID- 7874059 TI - Electrophoretic analysis of a gastric cancer-associated acid proteinase using a highly sensitive detection system. AB - A highly sensitive detection system for acid proteinase separated on polyacrylamide gel was established. This system consisted of two-dimensional electrophoresis, combined with isoelectric focusing and polyacrylamide gel electrophoresis, and casein clotting (caseogram). Human urine, serum and gastric tissues obtained from normal individuals and gastric cancer patients were analyzed using this system. The previous electrophoretic method was not sufficiently sensitive to detected small amounts of pepsinogen (PG) C in normal urine. However, the new rapid and sensitive method clearly revealed its presence. In gastric tissue containing cancer cells, an additional proteinase, which was not present in normal tissue, was detected and named medium moving proteinase (MMP). MMP resembled PGs in alkaline stability rather than the non-PG proteinase, slow moving proteinase (SMP). PMID- 7874060 TI - Effects of the acetylene compound from Atractylodes rhizome on experimental gastric ulcers induced by active oxygen species. AB - This study was conducted to determine the beneficial effects of treating digestive disorders of (6E,12E)-tetradecadiene-8,10-diyne-1,3-diol diacetate (TDEYA) detected in the plasma in hydrolyzed form: (6E,12E)-tetradecadiene-8,10 diyne-1,3-diol (TDEY), following the oral administration of a decoction of Atractylodes rhizome to rats. Assessment was also made of the efficacy of TDEYA in experimental gastric disorder models. Oral administration of TDEYA at doses of 300 to 500 mg/kg suppressed the formation of gastric lesions induced by indometacin in a dose-dependent manner. TDEYA at a dose of 200 mg/kg suppressed gastric lesions induced by an ischemia-reperfusion injury model. TDEYA at doses of 100 to 300 mg/kg did not show suppressive effects on water immersion stress induced gastric lesions. TDEYA showed no active oxygen species scavenging action, nor did it have any effect on superoxide dismutase activity in the stomach tissue. TDEYA at doses of 200 to 500 mg/kg significantly suppressed xanthine oxidase (XO) activity in the stomach tissue following its oral administration. The suppressive effects of TDEYA on lesion formation induced by indometacin and ischemia-reperfusion injury models would thus appear to be due in part to the inhibition of XO activity in the stomach tissue. PMID- 7874061 TI - Urinary and biliary metabolites of daidzin and daidzein in rats. AB - Examination was made of the urinary and biliary excretion of metabolites of daidzin and daidzein, the major components of roots of Pueraria lobata Ohwi (Leguminosae) in rats. The urine of rats administered daidzin orally contained four major metabolites, daidzein 7,4'-di-O-sulfate (M-1), daidzein 7-O-beta-D glucuronide (M-2), daidzein 4'-O-sulfate (M-3), daidzein (M-4), as determined from spectroscopic and chemical data. The urine of rats treated with daidzein contained M-2--M-4 in the above metabolites. Total cumulative amounts of the four metabolites excreted in the urine at 48 h following the oral administration of daidzin and daidzein were approximately 4.8% and 4.6% of the doses administered, respectively. The bile of rats administered daidzin orally contained M-1--M-4. Daidzein 7-O-beta-D-glucuronide 4'-O-sulfate (M-5), a major biliary metabolite, was identified by the high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectra. At least daidzin appeared to be hydrolyzed to aglycone after absorption in the body, and as a part of metabolites, M-1--M-4 having free hydroxyl, glucuronided or sulfated hydroxyls at the C-7 position, may then be excreted in the urine and bile. PMID- 7874062 TI - Improvement of aqueous solubility and rectal absorption of 6-mercaptopurine by addition of sodium benzoate. AB - The solubility of 6-mercaptopurine (6-MP) in water increased as the concentration of sodium benzoate or sodium hippurate in the solution increased. The solubility of 6-MP in 20% (w/v) sodium benzoate or sodium hippurate solution was about 6 fold larger than that of 6-MP alone. The stability constant of the soluble complex of 6-MP with sodium benzoate was estimated to be 2-8 M-1 from (1) phase solubility study and (2) analysis of chemical shifts observed in 1H-NMR. Partition of 6-MP from the saturated solution to n-octanol was also greatly increased by the addition of sodium benzoate or sodium hippurate, the degree being less in the latter. Administration of 6-MP with 20% (w/v) sodium benzoate to rat rectum resulted in enhanced absorption and the area under the plasma concentration-time curve was comparable to that obtained by intravenous administration (bioavailability = 100%), while the bioavailability after intrarectal administration of 6-MP with 20% (w/v) sodium hippurate was only 9%. The reason for the difference was discussed. PMID- 7874063 TI - In vivo microdialysis for the transdermal absorption of valproate in rats. AB - The suitability of sampling via microdialysis for a lipophilic drug, valproate (VPA), was evaluated by the elimination rate constant of VPA solution in an in vitro experimental first-order elimination system. The elimination rate constant of VPA in dialysate was found to be 0.43 +/- 0.05h-1, which was in good agreement with the real elimination rate constant (0.46 +/- 0.02h-1). A change in VPA concentration in the solution surrounding a microdialysis probe was well maintained by the microdialysis method, suggesting no adsorption between the membrane of the microdialysis probe and VPA. On the basis of the in vitro experiment, the effect of a penetration enhancer, 1-[2 (decylthio)ethyl]azacyclopentan-2-one (HPE-101), on the transdermal absorption of VPA was examined in rats by the use of microdialysis in vivo. An intradermal microdialysis was performed at a flow rate of 1.0 microliter/min for 7h after the dermal application of 50 mM VPA solution with or without 3% (w/v) HPE-101. HPE 101 increased the transdermal absorption rate of VPA by 80 times compared with the control. The microdialysis system was found to be quite useful for assessing the in vivo transdermal absorption of a lipophilic VPA. PMID- 7874064 TI - Mechanism of gastrointestinal absorption of glycyrrhizin in rats. AB - The mechanism of gastrointestinal absorption of glycyrrhizin (GZ) was examined in rats. Using an in situ loop technique, it was found that the intestinal absorption of glycyrrhetic acid (GA), a major metabolite of GZ, was larger than that of GZ and that the absorption of GA was larger in the small intestine than in the large intestine. Although GZ was poorly absorbable, both GZ and GA were detected in rat plasma after oral administration of GZ, suggesting that GZ can be absorbed in both parent and metabolite forms, although their bioavailabilities were low. GZ was hydrolyzed to GA by rat gastric and large-intestinal contents, but not by the small-intestinal contents. This hydrolysis was diminished after boiling of the gastrointestinal contents and was not observed in the gastrointestinal contents of kanamycin-treated rats. These results suggest that GZ is hydrolyzed by bacteria in the stomach and large-intestinal contents and that most of the GA formed is absorbed from the large intestine. Since GZ was extensively excreted in bile after intravenous administration, the first-pass elimination might be the reason for its low bioavailability, in addition to the poor mucosal permeability. PMID- 7874065 TI - Steric and electronic requirements for chloroflavone congeners as hepatic microsomal monooxygenase inducers. AB - We previously classified chloroflavone congeners into 3-methylcholanthrene (MC) type, phenobarbital (PB)-type and mixed (MC plus PB)-type inducers of hepatic microsomal monooxygenases in rats. In the present study, we examined the structure-activity relationship involved in the capability of congeners to induce the described regioselective O-demethylation activity of scoparone. The steric and electronic parameters of congeners were calculated by the MM2 molecular mechanics and Extended Huckel MO methods, respectively. The molecular rectangle area/depth ratios related well to the ratios of scoparone 6-/7-O-demethylation activities induced by the congeners. The molecular dimensions characterized the MC-type congeners as nearly planar molecules and the PB-type congeners as bulky and nonplanar. Moreover, the ratio of scoparone 6-/7-O-demethylation activities had significant correlation with both the LUMO energy (ELUMO) and the difference (delta E) between ELUMO and HOMO energy for the congeners. The ELUMO and delta E were less in the MC-type congeners than in the PB-type. These correlations suggest that the steric and electronic features of chloroflavone congeners are responsible for the induction of cytochrome P450 isozymes and associated monooxygenase activities. PMID- 7874066 TI - Influence of aging on acetohexamide reductase activities in liver microsomes and cytosol of male rats. AB - The influence of aging on the reductase activity of acetohexamide, an oral antidiabetic drug with a ketone group, was examined in liver microsomes and cytosol of male rats. Acetohexamide reductase activities in liver microsomes of male rats at 26 and 31 months of age were much lower than that in liver microsomes of male rats at 9 weeks of age. Testectomy markedly decreased acetohexamide reductase activity in liver microsomes of the 9-week old rats and the decreased enzyme activity was significantly increased by testosterone administration. These results indicate, at least in part, that aging decreases the enzyme activity by decreasing the secretion of testosterone from the testes. On the other hand, aging (26 months of age) did not affect acetohexamide reductase activity in liver cytosol of male rats, although the enzyme activity at 31 months of age was slightly but significantly lower than that in liver cytosol of male rats at 9 weeks of age. Testectomy or testosterone administration had no effect on the enzyme activity in liver cytosol of 9-week old male rats. PMID- 7874067 TI - Reaction of malondialdehyde with deoxyribonucleosides in the presence of acetaldehyde. AB - The reactivity of malondialdehyde (MDA) with deoxyribonucleosides in the presence of acetaldehyde (AA) was investigated. Although MDA is known to be reactive towards deoxyguanosine (GdR), deoxyadenosine (AdR) and deoxycytidine (CdR) under acidic conditions, MDA had only slight reactivity towards GdR under physiological pH. However, when AA was present, MDA exhibited much higher reactivity towards GdR, and a reaction with AdR also took place. PMID- 7874068 TI - Therapeutic effect of reticuloendothelial system (RES)-avoiding liposomes containing a phospholipid analogue of 5-fluorouracil, dipalmitoylphosphatidylfluorouridine, in Meth A sarcoma-bearing mice. AB - Reticuloendothelial system (RES)-avoiding liposomes are known to accumulate in tumor tissues due to passive targeting. Dipalmitoylphosphatidylfluorouridine (DPPF), a potent antitumor agent readily incorporated into the lipid bilayer, was embedded in RES-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA). The therapeutic effect of DPPF in PGlcUA liposomes was examined in tumor-bearing mice. Free or liposomal DPPF was injected intravenously into BALB/c mice bearing subcutaneously implanted Meth A sarcomas. The RES-avoiding liposomal formulation using PGlcUA was effective in reducing tumors, and prolonging survival time compared with free DPPF and also DPPF in conventional liposomes. Therefore, PGlcUA-liposomes might be of practical use as drug carriers for anticancer agents, especially their derivatives for embedding in liposomal membranes. PMID- 7874069 TI - Studies of cuticle drugs from natural sources. II. Inhibitory effects of Prunus plants on melanin biosynthesis. AB - The inhibitory effects of 50% ethanolic extracts from dried leaves of 38 plants collected in the herbal garden of Kinki University were investigated in vitro on melanin biosynthesis which is closely related to hyperpigmentation. Of the 38 extracts, Prunus yedoensis, P. zippeliana, P. amygdalus, P. persica, P. armeniaca, Thea sinensis and Chaenomeles sinensis showed a potent inhibition of tyrosinase, the enzyme which converts 3-(3,4-dihydroxyphenyl)alanine (dopa) to dopachrome in the biosynthetic process. Furthermore, the extracts from the leaves of P. yedoensis and P. zippeliana among the Prunus plants used in this experiment inhibited the production of melanin from dopachrome by autoxidation. These inhibitory effects of P. zippeliana on melanin biosynthesis were observed in cultured B-16 mouse melanoma cells. These results suggest that the leaves of P. zippeliana inhibit melanin biosynthesis which is involved in hyperpigmentation and could be used as a whitening agent for the skin. PMID- 7874070 TI - Relationship between lipophilicity and skin permeability of various drugs from an ethanol/water/lauric acid system. AB - The in vitro skin permeability of 16 drugs with a wide range of lipophilicity (log P; -0.95-4.40) was evaluated by the use of an ethanol/water (60/40) binary vehicle with or without lauric acid as a permeation enhancer. The enhancing effect by the addition of lauric acid to the ethanol/water (60/40) binary vehicle could be observed from the aspect of both permeation rate and lag time. The permeation rate increased with an increase in the hydrophilicity of the drugs. It was considered that lauric acid exerts an effect on both the polar and nonpolar regions of lipids of the stratum corneum, and the cooperative interaction of ethanol and lauric acid increases the participation of the polar pathway of drugs. The relationship between lipophilicity and skin permeability of the drugs from the ethanol/water (60/40) binary vehicle with lauric acid showed a parabolic shape, with its peak at a more hydrophilic range (log P; 0.19) compared with other past references (log P; 2-3). The ethanol/water (60/40) binary vehicle with lauric acid appears to be a good candidate as a vehicle for transdermal therapeutic systems for hydrophilic drugs. PMID- 7874071 TI - Physicochemical and hydrolytic characteristics of phenytoin derivatives. AB - To further clarify the pharmacokinetic characteristics of phenytoin (DPH) and its derivatives, DPH-1-methylnicotininate (MNDPH), valeroyl DPH (VADPH) and valproyl DPH (VPDPH), in plasma and brain, we have investigated their physicochemical properties and protein binding characteristics. Additionally, the hydrolytic conversion of these derivatives to DPH was also studied using small intestine, liver and brain tissues, as well as rat plasma. The log partition coefficient (PC) values of all derivatives were much higher than that of DPH. Judging from their pKa values (5.68 and 5.91 for VADPH and VPDPH, respectively) and pH solubilities, VADPH and VPDPH were acidic compounds, while MNDPH was basic. These data indicated that most fractions of VADPH and VPDPH existed as an ionized form (these fractions existed in an ionized form, 0.98 and 0.97, respectively) at physiological pH, whereas MNDPH existed as a unionized form under the same conditions. Rosenthal or Scatchard plots of the binding data of DPH and its derivatives to both rat plasma protein and bovine serum albumin (BSA) exhibited straight lines over their concentration ranges used, indicating that DPH and its derivatives have a single binding site on the protein. The binding potencies (K or n.Pt value) of the derivatives to both proteins were much greater than that of DPH. No DPH produced from VADPH and VPDPH was found in the biological fluids over a period of 24 h. However, the hydrolysis of MNDPH to DPH was observed in plasma and the tissues used, with the most rapid hydrolysis in the small intestine, and the hydrolysis rate constant in plasma was ca. 20-fold greater than that in the brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874072 TI - Detection of 1-acetamino-3-(1-naphthyloxy)-2-propanol as a new metabolite of propranolol. AB - 1-Acetamino-3-(1-naphthyloxy)-2-propanol which is an acetyl conjugate of N desisopropylpropranolol (AcNDP) was detected as a new metabolite of propranolol (PL) from the incubation medium of isolated rat hepatocyte system and from the urinary extracts of a patient under PL therapy as well as a healthy volunteer given PL. In the case of the hepatocyte systems, the optical selectivity of PL elimination and the metabolite formation were discussed by HPLC determination, and the effect of pretreatment by phenobarbital (PB) or 3-metylcholanthrene (3 MC) on the metabolism was also clarified. PMID- 7874073 TI - Naturally occurring virulence-attenuated isolates of Listeria monocytogenes capable of inducing long term protection against infection by virulent strains of homologous and heterologous serotypes. AB - Experimental infections of mice with strains of Listeria spp. isolated from contaminated food sources allowed discrimination of strains into those either exhibiting high, attenuated or low virulence. Compared to the highly virulent L. monocytogenes strain EGD, an attenuated strain such as L99 persisted for shorter times (5 versus 10 days) in the infected host. Using a tissue culture cell model of infection, we found that, although strain L99 was capable of accumulating actin like its virulent counterpart following invasion, it was unable to generate the polarized actin tails required for intracellular and cell-to-cell movement. Immunoblot analysis using specific antiserum to the ActA polypeptide, a molecule that is necessary for movement of the bacterium within the eucaryotic cell, indicated that a slightly truncated form of this polypeptide was produced in the L99 strain. Despite its reduced virulence, the attenuated strain L99 was just as effective in generating protection in immune mice as the highly virulent strains, albeit with a 1000-fold higher infective dose. Based on the results obtained from this study, we suggest that one of the mechanisms accounting for widespread resistance in humans to infection by Listeria may be due to asymptomatic infections by naturally occurring strains attenuated for virulence. PMID- 7874074 TI - Bacterial crude extracts or ribosomes are recognized similarly by peripheral and mucosal B cells. AB - Bacterial ribosomes have been shown to induce effective humoral and cellular immunological responses to whole microorganisms. In this study, the numbers of specific antibody producing cells directed towards Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae ribosomes or whole bacteria sonicates were compared in the peripheral blood and tonsils of 7 children, and in the tonsils, mesenteric and cervical lymph nodes of 10 sheep. No significant difference was noted between the two types of antigens, confirming that ribosomal preparations are able to mimic the immunogenicity of whole bacteria in the mucosae-associated lymphoid tissue. PMID- 7874075 TI - Evidence for the role of glycoprotein G of respiratory syncytial virus in binding of Neisseria meningitidis to HEp-2 cells. AB - Viral glycoproteins G and F are expressed on the surface of cells infected with respiratory syncytial virus (RSV). We investigated the role of these proteins in the previously reported enhanced binding of Neisseria meningitidis to RSV infected HEp-2 cells. Virus particles attached to bacteria were detected by immunofluorescence with flow cytometry. Binding of FITC-labelled bacteria to RSV infected cells was significantly inhibited by monoclonal antibody against glycoprotein G. Unlabelled bacteria interfered with binding of the anti-G monoclonal antibody to these cells. These interactions were not found with a monoclonal antibody against glycoprotein F. We propose that glycoprotein G of RSV expressed on the surface of infected cells might act as an additional receptor for meningococci. PMID- 7874076 TI - Differing signal requirements for the activation of macrophages from C3H/HeJ and C3H/OuJ mice. AB - Endotoxin-associated protein (EP) from Salmonella typhi stimulated the release of prostaglandin E2 (PGE2), interleukin-1 (IL-1), and interferon (IFN) activity in macrophages from the lipopolysaccharide (LPS) responder C3H/OuJ mouse strain. However, only PGE2 and IL-1 were stimulated by EP in macrophages from the LPS nonresponder C3H/HeJ mouse strain. LPS stimulated the release of PGE2, IL-1 and IFN activity in C3H/OuJ macrophages, but not in C3H/HeJ macrophages. The protein kinase C (PKC) activator phorbol myristic acid (PMA) stimulated PGE2 production in both strains but not IL-1 production, suggesting that signalling pathways other than PKC may be involved in IL-1 production. The calcium ionophore ionomycin stimulated PGE2 production in C3H/OuJ but not C3H/HeJ macrophages, suggesting a defective calcium-related pathway in the C3H/HeJ macrophages as compared to the C3H/OuJ cells. PMID- 7874077 TI - Outbreak of extended-spectrum beta-lactamase producing Serratia marcescens in an intensive care unit. AB - Serratia marcescens has recently been identified as an important etiological agent in nosocomial infections, and is considered to be an opportunistic pathogen agent in immunosuppressed patients undergoing long periods of intensive care. Research carried out in 1991 and 1992 showed that it was of epidemiological relevance in only 1-2% of clinical isolates at the Ospedale di Circolo, Varese, Italy. However, between 7 February and 11 October 1993, the incidence of cases attributable to S. marcescens had increased to 5%; 157 strains of Serratia marcescens were isolated from clinical specimens of 43 patients admitted to an intensive care unit; these strains, characterized by epidemic spread, showed the same pattern of multiresistance to antibiotics including monobactams and oxyimino cephalosporins. During the same period 23 isolates were also recovered from 18 patients admitted to wards other than the intensive care unit; these strains, characterized by a wide range of antibiotic susceptibility, were also sensitive to beta-lactam antibiotics with the exception of first generation cephalosporins. The production of extended-spectrum beta-lactamases (ES beta Ls) and their genetic determinism were studied. All the epidemic strains of S. marcescens resistant to ceftazidime, cefotaxime, ceftriaxone and aztreonam produced three different beta-lactamases with pI 5.4, 5.5 and 8.4 respectively. In contrast, non epidemic strains produced only a beta-lactamase with pI 8.4. The beta-lactamase with pI 5.5 was plasmid-mediated, hydrolizing ceftazidime and aztreonam, showing it to be an ES beta L; while the beta-lactamase with pI 5.4, although plasmid mediated, did not hydrolize monobactams or oxyimino-cephalosporins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874078 TI - Vaccination with Staphylococcus aureus fibrinogen binding proteins (FgBPs) reduces colonisation of S. aureus in a mouse mastitis model. AB - A mouse mastitis model was used to study the effect of vaccination with fibrinogen binding proteins and collagen binding protein from Staphylococcus aureus against challenge infection with S. aureus. The mice vaccinated with fibrinogen binding proteins showed reduced rates of mastitis compared with controls. Gross examination of challenged mammary glands of mice showed that the glands of mice immunized with fibrinogen binding proteins developed mild intramammary infection or had no pathological changes compared with glands from control mice. Histopathological examination of tissue sections from challenged glands showed that most glands from mice vaccinated with fibrinogen binding protein developed disseminated necrosis or had no pathological changes. A significantly reduced number of bacteria could be recovered in the glands from mice immunized with fibrinogen binding proteins as compared with controls. In a similar study, immunization of mice with collagen binding protein did not induce protection against challenge infection with S. aureus. PMID- 7874079 TI - Modulation of a specific humoral immune response and changes in intestinal flora mediated through fermented milk intake. AB - This study was undertaken to elucidate whether eating a fermented milk containing Lactobacillus acidophilus La1 and bifidobacteria could induce changes in intestinal flora and modulate the immune response in man. Volunteers consumed a fermented milk containing L. acidophilus La1 and bifidobacteria over a period of three weeks during which an attenuated Salmonella typhi Ty21a was administered to mimic an enteropathogenic infection. A control group ate no fermented foods but received the S. typhi Ty21a. Faecal flora analyses showed an increase in L. acidophilus and bifidobacterial counts during fermented milk intake. The specific serum IgA titre rise to S. typhi Ty21a in the test group was > 4-fold and significantly higher (P = 0.04) than in the control group. An increase in total serum IgA was also observed. These results indicate that lactic acid bacteria which can persist in the gastrointestinal tract can act as adjuvants to the humoral immune response. PMID- 7874080 TI - Long-term follow-up of patients with myocarditis and idiopathic dilated cardiomyopathy after immunomodulatory therapy. AB - The randomized clinical trial with interferon-alpha (IFN) or thymic hormones versus conventional therapy was conducted in patients with myocarditis and idiopathic dilated cardiomyopathy (IDC). We enrolled 180 patients to receive IFN (3-5 million units per day) for 3 months, thymomodulin (10 mg three times per week) for 2 months, or conventional therapy alone. Patients were followed-up for 7 years after the end of treatment. Left ventricular function, exercise tolerance and survival rate were significantly better at long-term follow-up in patients treated with IFN or thymomodulin, than in conventionally treated patients. These results implicate that immune modulating therapy might represent important contribution in the treatment of myocarditis and IDC. PMID- 7874081 TI - Streptokinase alleles and disease association in group A streptococci. AB - Allele-specific oligonucleotides were used for PCR-based typing of the streptokinase locus of group A streptococcal strains, including well characterized type strains, isolates from patients with acute poststreptococcal glomerulonephritis and strains from Aboriginal communities in the Northern Territory of Australia. The streptokinase SKN allele, previously thought to be associated with glomerulonephritis, was no more frequent in nephritogenic than in non-nephritogenic streptococcal strains in this collection. PMID- 7874082 TI - Multiple promoters of human choline acetyltransferase and aromatic L-amino acid decarboxylase genes. AB - The promoter regions of human choline acetyltransferase (ChAT) and aromatic L amino acid decarboxylase (AADC) genes have been analyzed by transient transfection assays. AADC gene is transcribed from two alternative noncoding first exons, 1N and 1NN, expressed in pheochomocytoma and hepatoma cells, respectively. 5' flanking sequences of exon 1 N (from 9000 to 147 bp) display promoter activity in SK-N-BE neuroblastoma cells, but not in MC-I-XC cholinergic neuroepithelioma cells, and in AADC-rich non-neuronal cells. On the contrary, 5' flanking sequences of exon 1 NN (from 1117 to 119 bp) display high promoter activity in human hepatoma cells HepG2, but not in SK-N-BE cells, suggesting high degrees of specificity of promoters N and NN for AADC-expressing neuronal and non neuronal cells, respectively. Preliminary evidence suggests that leukemia inhibitory factor suppresses the activity of the neuronal promoter in cultured sympathetic neurons. Two alternative first exons, R and M, have been localized in human ChAT gene, and the corresponding promoters characterized in cholinergic PC12 and NG-108-15 cells, and in non-cholinergic neuro2A cells. Several positively or negatively acting cis elements have been localized in the two promoters, as well as a cAMP-inducible, enhancer-like element in the second intron. Among the various cell lines studied, there was no correlation between promoter activities and the expression of the endogenous ChAT gene, suggesting that the fine-tuning of ChAT gene expression is controlled by silencer elements which remain to be localized. PMID- 7874083 TI - Differentiation of cholinergic neurons and physiological role of ciliary neurotrophic factor (CNTF). AB - Seven types of mRNA that differed in the 5'-non-coding region were identified for choline acetyltransferase of mouse spinal cord. These mRNAs were produced by differential splicing of pre-mRNAs transcribed from three different promoter regions. Two murine cholinergic cell lines, NS20Y and NG108-15, expressed M-type mRNA most abundantly. Using these cell lines, promotor activity in choline acetyltransferase gene was analyzed by transient assay of a reporter gene. The result indicated that there was promoter activity in the region upstream of the M type exon and enhancer activity in the intron downstream of the M-type exon, and that this region regulated neuron-specific expression of choline acetyltransferase activity. In contrast, R-type mRNA was exclusively expressed in cultured superior cervical ganglion cells and was markedly increased by ciliary neurotrophic factor (CNTF). To analyse the physiological role of CNTF, we constructed and screened a cDNA library from human sciatic nerves and isolated two types of cDNAs for human CNTF. Sequence analysis revealed that one type of cDNA corresponded to the normal mRNA, while the other type contained a 4 bp stretch insertion within the coding region, which caused frameshift from 39th amino acid with a stop codon 24 amino acids downstream. Analysis of genomic DNA for CNTF showed that there was a point mutation from G to A in the intron of the mutated allele, which created a new splice acceptor site and generated a new mRNA species with 4 bp insertion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874084 TI - Inhibition of neurotransmitter release by clostridial neurotoxins correlates with specific proteolysis of synaptosomal proteins. AB - Rat brain synaptosomes were used to study the effect of several clostridial neurotoxins on the neurotransmitter release. In this system the blockade of transmitter release correlated with the proteolytic activity of the toxins. Blockade of glutamate release was linked to selective proteolysis of one of the following synaptic proteins: synaptobrevin (BoNT/D, BoNT/F); SNAP-25 (BoNT/A, BoNT/E), or HPC-1/syntaxin (BoNT/C1). All the toxins used had an inhibitory effect on synaptosomes with the exception of BoNT/F. BoNT/F cleaved synaptobrevin in permeabilized synaptosomes but failed to produce the same effect on intact synaptosomes. PMID- 7874085 TI - Structure, diversity and synaptic localization of inhibitory glycine receptors. AB - The inhibitory glycine receptor (GlyR) mediates postsynaptic inhibition in spinal cord, brain stem and other regions of the vertebrate central nervous system. Biochemical and molecular approaches have identified different developmentally and regionally regulated GlyR isoforms that result from the differential expression of at least four genes coding for different variants of the ligand binding alpha subunit. Molecular studies have allowed identification of GlyR subunit domains implicated in ligand binding, channel formation and receptor assembly. At the postsynaptic membrane, the GlyR colocalizes with a 93-kDa tubulin-binding peripheral membrane protein, gephyrin. Antisense inhibition of gephyrin expression prevents GlyR accumulation at postsynaptic membrane specialization. Thus, gephyrin is essential for postsynaptic receptor topology. PMID- 7874086 TI - Distribution of synaptic markers in the retina: implications for synaptic vesicle traffic in ribbon synapses. AB - Synapses in the retina are present in two layers that can easily be distinguished morphologically: the thin outer plexiform layer (OPL) containing the photoreceptor ribbon synapses, and the more complex inner plexiform layer (IPL) containing mostly conventional synapses. In the current study we have used the exquisite spatial separation between ribbon and conventional synapses in the retina to investigate by immunocytochemistry the protein components of these two types of synapses. Our results show that all of the synaptic vesicle proteins tested are present in the ribbon synapses of photoreceptors except for the synapsins which were previously described to be absent from ribbon synapses. Thus, synaptic vesicles of ribbon and conventional synapses are likely to be very similar molecularly in spite of their different modes of trafficking. Furthermore, proteins with a likely function in synaptic vesicle docking and fusion (SNAP-25, munc-18) and endocytosis (dynamin) were also highly enriched in ribbon synapses, indicating that the basic machineries for synaptic membrane traffic are similar in ribbon and conventional synapses. Interestingly, photoreceptor cells contained only low concentrations of syntaxin I (which functions in the synaptic vesicle fusion complex) and GDI (which regulates the membrane association of rab-proteins as a function of GTP/GDP binding). These results raise the possibility that photoreceptors express other isoforms of these proteins, or that the functions of these proteins are not required for the tonical release mode of their synapses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874087 TI - Specific guidance and modulation of growth cone motility during in vivo development. AB - The hemidecussation of retinal fibers that occurs in mammals offers the opportunity to study several aspects of growth cone guidance in a single model system. Recent studies suggest that growth cones of crossed and uncrossed retinal fibers respond in differential manners when they contact cells at the optic chiasm midline, and that such contact interactions are the main event involved in their divergence. Observations of the in situ behaviors of these growth cones disclose that their guidance in this decision region involves two different processes: an orientational response, mediated by the selective guidance of the filopodia of frowth cones away or towards the midline of the optic chiasm, and a dynamic response, in which growth cones go through cycles of advance and pauses while in the optic chiasm. We hypothesize that these two aspects of growth cone motility represent two different aspects of the biology of growth cones in response to extrinsic cues, which are both used in their guidance during development. PMID- 7874088 TI - Environmental signals and neural crest cells. AB - Cell lineage analysis in both the central and peripheral nervous system of vertebrates has revealed that many neural progenitor cells are multipotent. These observations have raised the general issue of when and how such multipotent progenitors generate their various differentiated progeny. The environment of these progenitors controls the cell lineage decisions in the neural crest. This review considers the roles of the environmental signals in the context of the development of several different neural crest-derived lineages. PMID- 7874089 TI - A profile of outcome: 2 years after traumatic brain injury. AB - A group of 175 traumatic brain injury (TBI) patients who had undergone intensive rehabilitation at Bethesda Hospital attended a follow-up interview 2 years after injury. The majority of patients had suffered severe TBI. Outcome was documented in ten areas: medical/physical, mobility, activities of daily living (ADLs) accommodation, marital status, leisure and recreation, employment/study, communication, cognition and behaviour. Whilst most patients were physically independent and competent in personal and domestic activities of daily living, a third of the group were still reliant on assistance with community skills and transport, and more than half of those who previously had a job, were not working at 2 years post-injury. Around two-thirds of the sample reported cognitive, behavioural and emotional changes. There is clearly a need for ongoing community based support and assistance in dealing with practical difficulties and psychological problems as they are experienced after return to the community. PMID- 7874090 TI - A case of experiential hallucinations of unknown origins, or the mystery of the mime. AB - A case is described of repetitive familiar activities apparently accompanied by a hallucinated physical environment in an older brain-injured man with an amputation of the left temporal lobe. A parallel is drawn to the 'experiential hallucinations' described in psychomotor seizures and direct stimulation of the cortex. PMID- 7874091 TI - Prediction of employment status 2 years after traumatic brain injury. AB - The present study used a multivariate approach to investigate which of a range of variables relating to demographic factors, injury severity and degree of disability on admission to rehabilitation were the best predictors of employment status 2 years after traumatic brain injury (TBI). Subjects were 74 TBI patients who had been working prior to injury, had undergone rehabilitation at Bethesda Hospital and attended a review clinic 2 years after injury. A cross-validation sample consisted of a further 50 such subjects. Following preliminary analysis four input variables were selected: age under or over 40 at time of injury, Glasgow Coma Scale score on acute hospital admission, duration of post-traumatic amnesia and total score on the Disability Rating Scale (DRS) on admission to rehabilitation. Stepwise discriminant function analysis resulted in a discriminant function consisting of three variables--total score on the Disability Rating Scale, Glasgow Coma Scale Score and age--which correctly classified 74% of grouped cases. A second analysis using the original discriminant function correctly classified 68% of the cross-validation sample. Chi-square analysis showed no significant difference between these results, thus confirming these variables, in combination, as predictors of employment status 2 years after TBI. PMID- 7874092 TI - Late-onset post-concussion symptoms after mild brain injury: the role of premorbid, injury-related, environmental, and personality factors. AB - The present study investigated the possible role of a number of pre- peri-, and post-traumatic factors in the experience of post-concussion syndrome (PCS). These factors included: (1) history of premorbid risk factors, (2) severity of injury, and (3) post-morbid functioning and environmental factors. Subjects were 55 persons with mild brain injury. PCS was defined in terms of the severity and impact of 'late-onset' symptoms. Pre- and peri-traumatic factors were not associated with level of PCS symptom impact. Among post-traumatic factors, only level of psychological distress was strongly associated with impact level. The results suggest the importance of psychological factors in prolonged PCS. PMID- 7874093 TI - Late neurobehavioural symptoms after mild head injury. AB - The present study examined whether patients (n = 11) with post-concussional symptoms (PCS) 12-34 months after mild head injury (MHI) performed less well on selected neuropsychological tests than patients with MHI without PCS (n = 11) and healthy controls (n = 11). Patients with PCS were individually matched with controls for the time elapsed after the injury, age, sex, education and IQ. There were no overall gross differences between the groups in cognitive functioning, except for an isolated deficit on a sustained attention task. Post-hoc analysis of results obtained with two behavioural rating scales showed that patients with higher ratings on a post-concussive/cognitive complaints scale performed less well on a sustained attention task than subjects with lower ratings. PMID- 7874094 TI - Qualitative aspects of malingered memory deficits. AB - Much has been written in recent years on methods for detecting malingered memory deficits. However, previous research has focused exclusively on quantitative analyses of the data. The purpose of this study was to investigate more qualitative aspects of malingering. Undergraduates, community volunteers, psychiatric inpatients, and federal inmates who participated in analogue malingering studies were interviewed to elicit their self-reported strategies for faking memory impairment. Some of these subjects indicated that if they were to malinger they may show poor cooperation, aggravation and frustration, slow response times and frequent hesitations, and general confusion during the testing process. The strategy reported with the greatest frequency was to fake total amnesia (i.e. for personal identity, past knowledge, family and friends, and all aspects of the accident. PMID- 7874095 TI - Alteration of carbamazepine pharmacokinetics in patients with traumatic brain injury. AB - All patients admitted to a rehabilitation unit with closed-head injury over a 3 year period were reviewed for carbamazepine use exceeding 30 days in the hospital. Nine patients met the study inclusion criteria for age and duration of carbamazepine therapy. On review of the dose:serum concentration relationship, significant changes were noted in four patients. An initial increase in the dose:serum concentration ratio during the first few months of therapy was thought to reflect the well-known auto-induction of carbamazepine metabolism. However, unexplainable decreases in the dose:serum concentration occurred in the following months, and suggested alteration of carbamazepine pharmacokinetics in patients with traumatic brain injury. The finding may be important in determining the optimal approach to therapeutic drug monitoring of carbamazepine in brain-injured patients. PMID- 7874096 TI - N of 1 study: amantadine for the amotivational syndrome in a patient with traumatic brain injury. AB - Severe amotivation, apathy, and abulia, significantly retard rehabilitation following traumatic brain injury. Preliminary, uncontrolled research has suggested possible benefit with amantadine for this behavioural syndrome. This N of 1, double-blind, placebo-controlled study employed amantadine 100 mg three times daily in one such patient. Therapists and nurses completed inventories scoring efforts towards initiation of therapeutic activities during each session, progress in therapy, and participation in therapy. Four treatment periods (two active medication, two placebo), of 2 weeks duration, were completed. Across four therapists, and for both treatment pairs, the average effect score increased from 0.86 on placebo to 1.74 on amantadine (possible range 0-6, 3 = 'average'). There were no side-effects. The study suggests possible benefit with amantadine for patients with amotivational syndrome after traumatic brain injury; a randomized clinical trial appears warranted and required. PMID- 7874097 TI - The neuropsychological spectrum in traumatically head-injured persons. AB - The neuropsychological spectrum was investigated in a traumatically brain-damaged population. In this spectrum neuropsychological measures were regarded as the most biologically oriented, achievement measures as the most acquired skill oriented, and intellectual measures as having an intermediate position. It was found that the achievement measures correlated the most highly with each other, the intellectual measures intercorrelated to a lesser extent, and the intercorrelations of neuropsychological measures yielded a zero-order median correlation. It was further found that the correlations of measures with those in other categories had the same ranking. It was inferred that brain damage alters the pattern of the neuropsychological spectrum because of disproportionate impairment in the biological direction of the spectrum. PMID- 7874098 TI - Electrodermal response and outcome from severe brain injury. AB - The relation of electrodermal response measures to outcome from early post traumatic vegetative state (VS) was investigated in 15 brain-injured and five control subjects. Brain-injured subjects were in acute VS or persistent VS (PVS), or had recovered from acute VS (RVS). Significant group differences were found on all electrodermal response measures, primarily due to the greater amplitude, number and consistency of responses in control subjects. Group differences in electrodermal habituation and orientation to auditory tones reflected the absence of orientation in most RVS subjects and the absence of both habituation and orientation PVS subjects. The groups differed in their response to matching faces and names. All of the control subjects, two of five RVS subjects and none of five acute subjects produced significant responses. Surprisingly, two PVS subjects also produced significant responses. For acute subjects a positive outcome at 6 months post-trauma was associated with early electrodermal startle amplitude and baseline lability. These results indicate that electrodermal responsiveness is generally reduced following acute VS, even in subjects with a relatively good recovery. Greater electrodermal activity in early VS may be associated with better potential for recovery. PMID- 7874099 TI - Psychosocial and emotional sequelae of individuals with traumatic brain injury: a literature review and recommendations. AB - The psychosocial problems of decreased social contact, depression, and loneliness that occur for many with traumatic brain injury (TBI) create a major challenge for enhancing efforts at community re-entry. Despite dramatic physical progress within the first six months after injury, these psychosocial problems remain a persistent long-term problem for the majority of individuals with severe TBI. Researchers have consistently suggested that the psychosocial problems associated with TBI may actually be the major challenge facing rehabilitation. The majority of individuals who sustain TBI are young males between the ages of 19 and 25, who are in the early stages of establishing their independence in areas including friendships, leisure activities, intimate relationships, residence, and employment. The problem of social isolation and decreased leisure activities create a renewed dependence of the survivor on his/her family to meet these needs. In this article we review a large number of papers which examine the psychosocial and emotional sequelae for TBI patients. The results of those studies demonstrate four primary themes. The first theme depicts that individuals who experience severe TBI are at high risk for a significant decrease in their friendships and social support. The second theme relates to the lack of opportunity for establishing new social contacts and friends. The third theme relates to the decrease in leisure activities for individuals with severe TBI. Finally, anxiety and depression are found at high levels for prolonged periods of time following severe TBI. Several clinical recommendations are drawn from this literature review. They are: (1) Clinicians such as psychiatric social workers, psychologists, or psychiatrists may need to be called upon more quickly for intervention. The treating physiatrist cannot be expected to provide the insight and frequency of psychological services that may be necessary for many of these patients. (2) Since the literature seems to suggest that the presence of one psychosocial deficit, e.g., anxiety, will often be followed by other similar types of problems, e.g. depression, the treatment team needs to be sensitive to how rapidly these problems can cascade into a very dangerous situation. (3) Perhaps the most compelling recommendation we can make is for community rehabilitation specialists to focus significantly more energies and resources upon the psychological health of clients with TBI. Staff need to be trained to detect these signals that clients with TBI are often sending. It is apparent that psychosocial factors contribute to a rising obstacle level to community adjustment. PMID- 7874100 TI - Social competence and head injury: a new emphasis. AB - In the push for quantifiable outcome-based rehabilitation programmes, sensitivity to the integrity and uniqueness of the individual has been moved to the background. This has been particularly noticeable in the area of social skills therapy for persons who have suffered a traumatic head injury. We review some of the patterns of normal communication, with particular reference to roles, communicative relationships and individual differences, in order to clarify the difficulties in making clinical judgements about these skills. We propose a shift in focus to establishing a symmetrical therapeutic relationship in which communication is based on respect rather than structure and control. We utilize the clients' insights into their own social communication problems to enable them to be primary managers of their activities. The clinician's responsibility is not only to be a resource but also to be actively involved in the therapeutic process by reviewing his or her own social communication patterns in and outside of the therapy sessions. We argue that, with this perspective, activities can focus on principles of communication rather than specific skills, resulting in improved generalization and long-term outcome. PMID- 7874101 TI - Building partnerships with parents of school-age children with communication disorders. AB - This article discusses the strategies for building partnerships with parents and for achieving collaboration among parents, teachers, and speech-language pathologists, all of whom are agents who will influence the process of the child's speech-language learning process. The changes in educational philosophy and related laws, and in the role of parents, are discussed. Common concerns of parents of children with communication disorders are discussed. PMID- 7874102 TI - Preparing students to work with families: undergraduate and graduate education. AB - This article focuses on the preparation of undergraduate and graduate students in Human Communication Sciences and Disorders, for provision of services that involve families. The author discusses the identification of a family-oriented clinical model, the identification of the prerequisites needed for students' entry into clinical training in the family-oriented model, the prerequisites that students need to develop for independent clinical practice, and the management of common challenges faced by students as they participate in the family-oriented model. Evaluation forms are provided to assist the supervisor in the preparation of student clinicians. PMID- 7874103 TI - Meeting the needs of the non-English-speaking parents of a communicatively disabled child. AB - This article provides some suggestions for clinicians to assist them in working effectively with students and families who do not speak English or for whom English is a second language. Included is a brief review of the diversity of languages and cultures represented by families living in the United States. There are differences in the ways in which the families view language development, the educational process, and their roles in working with their children. It is important to learn to respect the families' views on language development and education, learn how to work with an interpreter, and how to help the families help their children. Communication with the families and their involvement in the process of assisting their children's development of language skills should be individualized to accommodate the families' views, languages, and available resources. PMID- 7874104 TI - Therapy at home: Vygotskian perspectives on parental involvement. AB - In this article a case study is used to demonstrate the contributions of parents to the diagnostic and intervention process in home-based therapy. Two assumptions of Vygotskian theory form the bases for this conceptualization: (1) that individual mental functioning has social origins, and (2) that individuals appropriate their ways of talking and thinking from the sociocultural routines and practices in which they are embedded. Given these assumptions, the role of the parent is presented as essential to assessment and treatment because the talk of the child is jointly constructed with them and within home activities. The case study functions as an example of how parents are instrumental to our therapeutic work. PMID- 7874105 TI - Recommendations for clinicians based on parents' experiences. AB - Three mothers of children with severe communication disabilities describe their experiences with speech-language pathologists and the intervention process. The parents were asked open-ended and descriptive questions. Their responses provide valuable insights and direction for professionals interested in working more closely with families of children with disabilities. The mothers describe their role as primary case managers for their children's treatment programs. They identify the type of speech-language pathologist they prefer to work with their child and the professional guidance they find most helpful. Several recommendations for communication disorders professionals evolved from the discussion. PMID- 7874106 TI - Family-centered care: thriving in Hawaii under Part H. AB - Hawaii's system of prevention and early intervention embodies Part H principles that a child with a disability is first surrounded by a family, then by a community. Since 1986, families in Hawaii have been active in early intervention, first by persuading the governor to name the Department of Health as the lead agency, and then by writing much of the original grant application, interviewing and selecting staff members, and serving on the Hawaii Early Intervention Coordinating Council and its subcommittees. Families helped develop Hawaii's broad definition of the population to be served and were vocal advocates before the legislature to obtain funding for the program. Under Part H, Hawaii serves 6% of all children under the age of three, a larger percentage than any other state. Services focus on the family's needs as much as on the child's. The Individualized Family Support Plan (IFSP), developed jointly by the parents and professionals, recognizes families as the final decision-maker on the IFSP team. Families choose options that fit their needs. IFSP meetings are at times and places convenient to families and, to the extent feasible, in the family's native language. Care coordinators, of whom several are parents of children with special needs, monitor services to ensure that families receive quality care. Families receive (1) services at no cost, (2) preference when applying for positions in the Zero-to-Three Hawaii Project, and (3) compensation when serving in advisory or policy-making areas. In Hawaii, families are the center of early intervention services. PMID- 7874107 TI - A P1-based physical map of the region from D17S776 to D17S78 containing the breast cancer susceptibility gene BRCA1. AB - BRCA1, a breast and ovarian cancer susceptibility locus, has been isolated and maps to 17q21. A physical map of the BRCA1 region which extended from the proximal boundary at D17S776 to the distal boundary at D17S78 was constructed and consists of 51 sequence tagged sites (STSs) from P1 and YAC ends, nine new short tandem repeat (STR) polymorphic markers, and eight identified genes. The contig, which spans the estimated 2.3 Mb region, contains 29 P1s, 11 YACs, two BACs, and one cosmid. Based on key recombinants in two linked families, BRCA1 was further localized to a region bounded by D17S1321 on the proximal side and D17S1325 on the distal side. Within this estimated 600 kb region, the contig was composed completely of P1s and BACs ordered by STS-content mapping and confirmed by DNA restriction fragment fingerprinting. PMID- 7874108 TI - The detailed characterisation of a 400 kb cosmid walk in the BRCA1 region: identification and localisation of 10 genes including a dual-specificity phosphatase. AB - We have produced a detailed physical and transcriptional map of a 400 kb region within the narrowest flanking markers known to contain the hereditary breast and ovarian susceptibility gene, BRCA1. The approach described here has avoided the problems of chimaerism, instability and rearrangements commonly observed in yeast artificial chromosomes by converting the YAC clones into ordered chromosome 17 specific cosmid contigs and joining these contigs by cosmid end-walking. A detailed long-range restriction map provided a framework for the cosmid contig assembly and further refines existing physical mapping data. We have used a combined approach towards the isolation of the genes housed within these cosmids. This has resulted in the isolation and precise localisation of eight novel genes, including a novel G protein and an endogenous retrovirus related to the HERV-K family, and the previously described dual-specificity VHR phosphatase and MOX1 homeobox genes. PMID- 7874109 TI - RET proto-oncogene mutations in French MEN 2A and FMTC families. AB - Constitutional mutations of the RET proto-oncogene have been identified in multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC) families. We sequenced RET exons 10 and 11 in 86 unrelated patients with an inherited predisposition to MTC (excluding MEN 2B). Germ-line mutations were identified in 93% of the MEN 2A families and 67% of the FMTC families tested. All were missense mutations affecting one of three cysteines in the extracellular domain of the RET tyrosine kinase receptor. The prevalence of phaeochromocytoma and hyperparathyroidism was significantly higher in families with a mutation of cysteine 634. These data confirm the preferential localisation of MEN 2A and FMTC associated mutations and the strong correlation between clinical manifestations and the position of RET mutation. Although direct sequencing of RET exons 10 and 11 allows the identification of a constitutional mutation in a large proportion of MEN 2A and FMTC families, our data sustain the existence of other MTC predisposing mutations elsewhere in RET coding or regulating region. PMID- 7874110 TI - Multiple deletions of mtDNA in two brothers with sideroblastic anemia and mitochondrial myopathy and in their asymptomatic mother. AB - Two brothers presented with a clinical picture characterized by sideroblastic anemia, mild pancreatic insufficiency and progressive muscle weakness. The presence of an associated permanent basal lactic acidemia raised the suspicion of a mitochondrial disease. A muscle biopsy performed in both siblings proved the presence of a significant number of ragged-red fibers, and respiratory chain enzymatic determinations demonstrated a reduced activity of complexes I, III and IV. Mitochondrial DNA studies disclosed the presence of multiple deletions both in skeletal muscle and, to a lesser extent, in leukocytes. Similar, but not identical deletions were also present in the leukocytes and muscle from their mother. Deletions were flanked by short direct repeats. We conclude that such patients suffer from a familial form of mitochondrial disease clinically resembling Pearson's syndrome, with a probably autosomal dominant inheritance. PMID- 7874111 TI - Two 5q13 simple tandem repeat loci are in linkage disequilibrium with type 1 spinal muscular atrophy. AB - The gene for the common recessive neuromuscular disorder spinal muscular atrophy (SMA) has been previously mapped to chromosome 5q. We report here linkage disequilibrium analyses of two polymorphic simple tandem repeat (STR) sequences which map into the critical region of 5q13 containing the SMA gene. The polymorphisms presented are constituents of CATT-1, a complex STR which is present in as many as four or more copies per chromosome 5. The PCR can amplify as many as eight CATT-1 products of different sizes from genomic DNA samples due to differing numbers of CA dinucleotides at each STR location (sublocus). Oligonucleotide primers for two of these subloci have been developed for specific PCR assays; a variety of allele sizes can be generated with each assay and, in some cases, no amplification products are detected due to null alleles. The genotyping of 149 SMA Type 1 chromosomes and 142 normal chromosomes from Canadian and American kindreds reveals the presence of significant linkage disequilibrium between the null allele of the sublocus referred to as CATT-40G1 and mutation(s) causing SMA Type 1 (Werdnig-Hoffmann disease). Allele 2 of the second sublocus, CATT-192F7, is also in linkage disequilibrium with SMA Type 1 although the degree of this association is less than that found for CATT-40G1. The proximal and distal STRs from the critical region, D5S435 and D5S351, showed no linkage disequilibrium with SMA. The data presented here will serve as a framework for future linkage disequilibrium analyses, expediting the final stage of the search for the SMA gene. PMID- 7874112 TI - Cloning and characterization of a new human Xq13 gene, encoding a putative helicase. AB - We describe the cloning and characterization of a new human Xq13 gene (XH2), extending over a 220 kb genomic stretch between MNK and DXS56. The gene, which undergoes X-inactivation, contains a 4 kb open reading frame and encodes a putative NTP-binding nuclear protein homologous to several members of the helicase II superfamily. The murine homologue maps to the syntenic genetic interval, between Pgk1 and Xist. In situ hybridization studies in mouse reveal precocious, widespread expression of the murine homologue of XH2 at early stages of embryogenesis, and more restricted expression during late developmental stages and at birth. XH2 is a new member of an expanding family of proven and putative helicases, sharing six conserved, collinear domains. In particular, the XH2 protein shows homology with yeast RAD54. Type II helicases have been implicated in nucleotide excision repair and the initiation of transcription. This new gene, represents a potential candidate for several genetic disorders mapped to human Xq13. PMID- 7874113 TI - Accumulation of genetic alterations during esophageal carcinogenesis. AB - Using polymerase chain reaction amplification of microsatellite regions in DNA from 11 epithelial dysplasias of the esophagus and 21 early squamous cell carcinomas, we were able to detect frequent loss of heterozygosity (LOH) on chromosomes 3p21.3 and 9q31 even in low-grade dysplasias. In contrast, we observed frequent LOHs on chromosomes 9p22 and 17p13 (TP53 locus) only in high grade dysplasias and carcinomas, but not in any low-grade dysplasias. Analysis of LOH at the same four chromosomal regions in DNA of five additional minimal carcinomas and accompanying dysplastic lesions revealed loss of alleles at the loci on 3p21.3 and 9q31 throughout various degrees of dysplasia and carcinoma; again, LOHs on 9p22 and 17p13 occurred only in high-grade dysplasia and carcinoma in situ. Our results indicated that inactivation of putative tumor suppressor genes on 3p21.3 and 9q31 may be early genetic events during esophageal carcinogenesis, and that additional genetic alterations on 9p22 and 17p13 probably play roles in progression. PMID- 7874114 TI - Mitochondrial DNA polymorphism in disease: a possible contributor to respiratory dysfunction. AB - Intergenomic variation in the human mitochondrial genome was examined in 27 mtDNA sequences using a pairwise analysis technique. Analysis of 16 of these mtDNA sequences from patients with mitochondrial cytopathies indicated a wide range between different mitochondrial genes in the degree of nucleotide variation from the standard Cambridge sequence. Mean complex I polymorphic frequencies in cytopathic (CPEO, MERRF, MELAS and LHON collectively) patients and in LHON patients differed significantly from controls (P < or = 0.05, t). Total mean sequence divergence (mean number of diverging nucleotides between two sequences per 100 bp) over the entire mtDNA coding region was 0.21% for cytopathies (n = 16) as opposed to 0.18% for a control group (n = 4). Within the cytopathy group, the greatest pairwise divergence was observed in ND3 and ND6 subunits of complex I (0.46 and 0.70% respectively) and the magnitude of specific gene divergences differed considerably from those observed for the corresponding genes in the control population. The extent to which the increased variation in ND3 and ND6 is a general phenomenon applicable to all subjects rather than a finding specific to cytopathies cannot be stated with certainty given the small control group. Regardless as to which of these suggestions is correct, the possibility exists that increased nucleotide variation in certain mitochondrial ND subunits may contribute to respiratory inefficiency through a cumulative effect of a series of polymorphisms of minor individual mutagenic potential. PMID- 7874115 TI - Human muscle glycogenosis due to phosphorylase kinase deficiency associated with a nonsense mutation in the muscle isoform of the alpha subunit. AB - Heritable phosphorylase kinase (Phk) deficiency is responsible for several forms of glycogen storage disease in humans and animals that differ in mode of inheritance and tissue-specificity. Mutations affecting different subunits and isoforms of Phk are expected to contribute to this heterogeneity. In the present study, we have investigated a case of muscle-specific, adult-onset Phk deficiency. The coding sequences of three candidate genes were analyzed by RT-PCR and sequencing: the muscle isoform of the alpha subunit (alpha M), a muscle specifically expressed exon of the beta subunit, and the muscle isoform of the gamma subunit. Whereas the latter two sequences were found to be normal, we identified a nonsense mutation in alpha M. The condition of this patient therefore is a human homolog of the X-linked muscle Phk deficiency of I-strain mice. To our knowledge, this is the first description of a human Phk deficiency mutation. PMID- 7874116 TI - The relationship between mitochondrial genotype and mitochondrial phenotype in lymphoblasts with a heteroplasmic mtDNA deletion. AB - The relationship between mitochondrial genotype and mitochondrial phenotype was investigated in lymphoblasts derived from a patient with the Pearson syndrome. In 70% of the mtDNA of this Pearson cell line a deletion from within the COX II gene to within the ND5 gene was present. The deletion led to a reduced expression of the deleted genes, but the severely lowered synthesis of e.g. subunit II of cytochrome c oxidase was not reflected in a significant decrease in the cytochrome c oxidase activity. Moreover, there were no obvious differences between control cells and Pearson cells regarding the capacity for oxidative phosphorylation. Analysis of the synthesis and assembly of both nuclearly and mitochondrially encoded subunits of cytochrome c oxidase showed that normally mtDNA-encoded polypeptides are produced in excess. This overproduction fully explained the discrepancy between the severe defect in the expression of the mitochondrial genome and the normal mitochondrial function in the Pearson cells. These data demonstrate that the expression of one or more mitochondrial genes can be reduced specifically at intermediate percentages of deleted mtDNA. However, the data also suggest that whether or not a lower expression of mitochondrial genes encoding subunits of enzymes involved in oxidative phosphorylation influences the normal function of these enzymes depends on the relative abundance of the mitochondrial subunits in tissues or cells with deleted mtDNA. PMID- 7874117 TI - A single amino acid substitution (G103D) in the type II collagen triple helix produces Kniest dysplasia. AB - Kniest dysplasia is a moderately severe chondrodysplasia phenotype that results from mutations in the gene for type II collagen, COL2A1. Characteristics of the disorder include a short trunk and extremities, mid-face hypoplasia, cleft palate, myopia, retinal detachment, and hearing loss. Recently, deletions of all or part of exon 12 have been identified in individuals with Kniest dysplasia, suggesting that mutations within this region of the protein may primarily result in the Kniest dysplasia phenotype. We used SSCP to analyze an amplified genomic DNA fragment containing exon 12 from seven individuals with Kniest dysplasia. An abnormality was identified in one patient. DNA sequence analysis demonstrated that the patient was heterozygous for a G to A transition that implied substitution of glycine103 of the triple helical domain by aspartate. The mutation was not observed in DNA from either of the clinically unaffected parents of the proband. Protein microsequencing demonstrated expression of the abnormal allele in cartilage. These data demonstrate that point mutations which result in single amino acid substitutions can produce Kniest dysplasia and further support the hypothesis that alteration of a domain, which includes the region encoded by exon 12, in the type II collagen protein leads to this disorder. PMID- 7874118 TI - Human APC gene expression in rodent colonic epithelium in vivo using liposomal gene delivery. AB - Mutations or loss of the APC tumor-suppressor gene is important for the development of colorectal polyps and cancers, but little is known about the function of this gene in normal tissue. To study the role of APC and other genes in colonocytes in vivo, a system was developed whereby transient expression of genes is established in normal rodent colonic epithelium, using liposomal gene delivery by rectal catheter infusion. Expression of a beta-galactosidase reporter gene and of the human APC gene under a constitutive promoter is demonstrated. A high efficiency of transfection is maintained, with close to 100% of epithelial cells expressing the introduced gene. Expression is transient and does not persist beyond 4 days, consistent with the normal turnover time of gut epithelium, but it can be maintained by repeated treatments. Human APC was expressed for three weeks under these conditions at approximately one-tenth the level of the endogenous APC gene, and no toxicity was observed beyond that attributed to repeated rectal enemas. These results reveal that in vivo expression of exogenous gene is feasible using a liposomal delivery system and suggest a method to further study the physiologic role of APC or other genes in the interrelated process of colonic epithelial proliferation and differentiation. PMID- 7874119 TI - Cloning the shared components of complex DNA resources. AB - The complex and repetitive nature of mammalian genomes limits the ability of conventional molecular techniques to recover sequences of interest. Here we describe a rapid and simple procedure for the direct cloning of sequences which are coincident between DNA mixtures of whole genome complexity. The system, called end ligation coincident sequence cloning (EL-CSC), can enrich coincident DNA by greater than 10(6)-fold and overcomes problems associated with repetitive elements. Applying EL-CSC to various paired DNA resources enables the facile cloning of both genomic markers and novel genes. To demonstrate the power of the method we have i) selectively purified single copy sequences from a complete genome, and ii) isolated gene fragments from 260 kb of cloned genomic DNA. PMID- 7874120 TI - Rapid identification of gene sequences for transcriptional map assembly by direct cDNA screening of genomic reference libraries. AB - We have used the direct cDNA screening protocol to identify sequences transcribed in cerebral cortex from a reference library of human Xq28. To derive coding sequences from these genomic clones, we first identified fragments containing transcribed sequences and subjected these to exon trapping or to partial sequencing and analysis by Grail. In a preliminary analysis of three clones, coding sequences from two novel genes expressed in brain were identified. This method allows the rapid identification of coding sequences of genes expressed in specific tissues without recourse to cDNA libraries. The approach is amenable to large scale applications and should be useful for isolating candidate disease genes and in particular for assembling integrated transcriptional maps from large genomic regions. PMID- 7874121 TI - A frameshift mutation in the mouse alpha 1 glycine receptor gene (Glra1) results in progressive neurological symptoms and juvenile death. AB - The neurologic mutant mouse, oscillator, is characterized by a fine motor tremor and muscle spasms that begin at 2 weeks of age and progressively worsen, resulting in death by 3 weeks of age. We report the localization of the oscillator mutation to the central region of mouse Chr 11, and demonstrate its allelism with spasmodic, a recessive viable neurological mutation which displays excessive startle. Oscillator is caused by a microdeletion in the gene coding for the alpha 1 subunit of the adult glycine receptor (Glra1). Glra1 assembles into a pentameric complex with the beta subunit of the glycine receptor (3 alpha (1)2 beta 5) to form a glycine-gated chloride channel. This receptor is the major adult glycine receptor, and the site of action of the poison strychnine. The oscillator deletion causes a frameshift resulting in loss of the highly conserved third cytoplasmic loop and fourth transmembrane domain of the protein. Membranes isolated from oscillator homozygote spinal cords display a 90% reduction in glycine-displaceable strychnine binding. This lack of ligand binding function confirms that oscillator is a complete loss of function allele. The oscillator mutation provides evidence that although at least four different alpha subunits exist for the glycine receptor, none of the other subunits can compensate for the loss of alpha 1 function. Mutations which impair GLRA1 function in humans have been shown to cause dominant familial startle disease. The identification of the oscillator mutation suggests that severe loss of function alleles in humans would result in prenatal or neonatal lethality. PMID- 7874122 TI - Myotonic dystrophy CTG repeats and the associated insertion/deletion polymorphism in human and primate populations. AB - Myotonic dystrophy (DM) is associated with abnormal expansions of the CTG repeats in the 3' untranslated region of its gene. Previous studies in individuals of European origin demonstrated strong linkage disequilibrium between different CTG repeat length alleles and an Alu element insertion/deletion polymorphism in intron 8 of the DM gene: CTG11-13 chromosomes were almost exclusively associated with the deletion allele, while chromosomes with five or 19-30 repeats or disease chromosomes were only found on the insertion allele. One of the models suggested by these results proposed that the triplet repeats on insertion-associated chromosomes were particularly prone to mutation. Studies of other triplet repeat disorders have suggested that arrays of perfect repeats are more prone to instability than those that are interrupted. We have examined the evolution of this locus by typing a variety of primates and samples drawn from several different human populations for both CTG repeat length and the insertion/deletion polymorphism. DM gene sequences from different primates revealed inter- and intraspecies variability in the number of CTG repeats. Human chromosomes with five repeats or 11-13 repeats (the two major modes of the human CTG repeat distributions) showed no evidence of preferential stabilization of these repeat sizes by imperfect sequences. The insertion and deletion allele frequencies showed large interpopulation variation and the degree of association between these alleles and various CTG repeat lengths is not nearly as complete as was previously supposed. We have found deletion alleles carrying long normal (> 19) CTG repeats and insertion alleles associated with CTG11 - 13 in two african populations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874123 TI - Linkage of a locus for carbohydrate-deficient glycoprotein syndrome type I (CDG1) to chromosome 16p, and linkage disequilibrium to microsatellite marker D16S406. AB - Carbohydrate-deficient glycoprotein syndrome type I is a multisystem disease with early severe nervous system involvement. The disease, which is inherited as an autosomal recessive trait, is biochemically characterized by complex defects in the terminal carbohydrate residues of a number of serum glycoproteins. This can be most readily detected in transferrin. A whole genome scan was initiated in order to localize the gene (CDG1) with linkage techniques. We analyzed individuals from 25 CDG1 pedigrees with several highly polymorphic microsatellite markers and after exclusion of about 30% of the genome linkage was detected with markers located in chromosome region 16p. The lod score (Zmax) was above 8 (theta max = 0.00) for several markers in this region. In order to further localize the CDG1 gene, recombination and linkage disequilibrium analyses were performed. Recombination events in some pedigrees indicated that the CDG1 gene is located in a 13 cM interval between microsatellite markers D16S406 and D16S500. Furthermore, allelic association was shown for marker D16S406 indicating that the CDG1 gene is located close to this. No heterogeneity could be detected in the European family material tested by us. The positions of cytogenetically localized flanking markers suggest that the location of the CDG1 gene is in chromosome region 16p13.3-p13.12. PMID- 7874124 TI - Isolation of CA dinucleotide repeats close to D6S105; linkage disequilibrium with haemochromatosis. AB - The gene for hereditary haemochromatosis (HC) is linked to HLA-A and D6S105 on chromosome 6p. Both markers have also been reported to display linkage disequilibrium with the disease. However, their physical localization relative to one another has not been established. We demonstrate by fluorescent in situ hybridisation that D6S105 lies at least 1-2 Mb telomeric of HLA-A. The haemochromatosis critical region extending from proximal of HLA-A to distal of D6S105 is therefore large. To improve the genetic resolution in this region more highly polymorphic markers are required. We have therefore isolated three novel CA dinucleotide repeats close to D6S105. A linkage disequilibrium study, with two of these microsatellites, in HC patients and controls lends support to the conclusion that D6S105 is a close marker to the haemochromatosis gene. PMID- 7874125 TI - Diverse mutations of the P gene among African-Americans with type II (tyrosinase positive) oculocutaneous albinism (OCA2). AB - Type II (tyrosinase-positive) oculocutaneous albinism (OCA2) is an autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in the skin, hair, and eyes. OCA2, which we have shown results from mutations of the P gene in Caucasians, is the most prevalent type of oculocutaneous albinism in African and African-American patients with OCA. We have identified abnormalities of the P gene in seven unrelated African-American patients with OCA2, including three large deletions, two small in-frame deletions, and six different point mutations. None of these appears to be predominant among African-American patients with OCA2. PMID- 7874126 TI - Isolation and partial characterization of a chloride channel gene which is expressed in kidney and is a candidate for Dent's disease (an X-linked hereditary nephrolithiasis). AB - Dent's disease, an X-linked renal tubular disorder, is a form of Fanconi syndrome which is characterized by proteinuria, hypercalciuria, nephrocalcinosis, kidney stones and renal failure. Previous studies localised the gene responsible to Xp11.22, within a microdeletion involving the hypervariable locus DXS255. Further analysis using new probes which flank this locus indicate that the deletion is less than 515 kb. A 185 kb YAC containing DXS255 was used to screen a cDNA library from adult kidney in order to isolate coding sequences falling within the deleted region which may be implicated in the disease aetiology. We identified two clones which are evolutionarily conserved, and detect a 9.5 kb transcript which is expressed predominantly in the kidney. Sequence analysis of 780 bp of ORF from the clones suggests that the identified gene, termed hCIC-K2, encodes a new member of the CIC family of voltage-gated chloride channels. Genomic fragments detected by the cDNA clones are completely absent in patients who have an associated microdeletion. On the basis of the expression pattern, proposed function and deletion mapping, hCIC-K2 is a strong candidate for Dent's disease. PMID- 7874127 TI - A two basepair deletion in the SOD 1 gene causes familial amyotrophic lateral sclerosis. PMID- 7874128 TI - A missense mutation (S63L) in alpha-L-fucosidase is responsible for fucosidosis in an Italian patient. PMID- 7874129 TI - Mutational analysis of the hMSH2 gene reveals a three base pair deletion in a family predisposed to colorectal cancer development. PMID- 7874130 TI - Nonsense and missense mutations of the muscle chloride channel gene in patients with myotonia congenita. PMID- 7874131 TI - Isolation of a de novo mutant myocardial beta MHC protein in a pedigree with hypertrophic cardiomyopathy. PMID- 7874132 TI - Three sequence polymorphisms in the PDC gene. PMID- 7874134 TI - Three dinucleotide repeat polymorphisms at the ataxia-telangiectasia locus. PMID- 7874133 TI - Ten microsatellite polymorphisms mapped to chromosome 16. PMID- 7874135 TI - A (CA)n repeat polymorphism near the 3' end of the CBG gene. PMID- 7874136 TI - Cryptic trinucleotide repeat polymorphism in the POMC gene. PMID- 7874137 TI - Dinucleotide repeat polymorphism at the human CCKBR locus. PMID- 7874138 TI - Dinucleotide repeat polymorphism at the HPR locus. PMID- 7874139 TI - Dinucleotide repeat polymorphism at the human PDGF RB gene. PMID- 7874140 TI - Three dinucleotide repeat polymorphisms proximal to the D2S123 locus. PMID- 7874141 TI - D17S1175: dinucleotide repeat polymorphism 5' to CHRNE. PMID- 7874142 TI - DXYS161 detects a VNTR locus in the pseudoautosomal region. PMID- 7874143 TI - Trinucleotide repeat microsatellite in the 5' untranslated region of HLA-F. PMID- 7874144 TI - A polymorphism in the human coagulation factor V gene. PMID- 7874145 TI - TaqI RFLP for the IL2RA locus. PMID- 7874146 TI - (ATTT)n-tetranucleotide repeat polymorphism in the 5'-flanking region of the UGB gene. PMID- 7874148 TI - New human DNA polymorphisms submitted to the genome data base. PMID- 7874147 TI - Dinucleotide repeat polymorphism from a cosmid containing the human anion exchanger isoform 3 (SLC2C) gene. PMID- 7874149 TI - Vitamin/mineral supplement use among athletes: a review of the literature. AB - Vitamin/mineral supplements are often used by athletes as ergogenic aids to improve performance. This paper reviews studies of the prevalence, patterns, and explanations for vitamin/mineral supplement use among athletes. Fifty-one studies provided quantitative prevalence data on 10,274 male and female athletes at several levels of athletic participation in over 15 sports. The overall mean prevalence of athletes' supplement use was 46%. Most studies reported that over half of the athletes used supplements (range 6% to 100%), and the larger investigations found lower prevalence levels. Elite athletes used supplements more than college or high school athletes. Women used supplements more often than men. Varying patterns existed by sport. Athletes appear to use supplements more than the general population, and some take high doses that may lead to nutritional problems. Sport nutritionists should include a vitamin/mineral supplement history as part of their dietary assessment so they can educate athletes about vitamin/mineral supplements and athletic performance. PMID- 7874150 TI - The effects of aerobic and anaerobic exercise conditioning on resting metabolic rate and the thermic effect of a meal. AB - This study examined resting metabolic rate (RMR) and thermic effect of a meal (TEM) among athletes who had participated in long-term anaerobic or aerobic exercise. Nine collegiate wrestlers were matched for age, weight, and fat-free weight with 9 collegiate swimmers. Preliminary testing included maximal oxygen consumption, maximal anaerobic capacity (MAnC) for both the arms and the legs, and percent body fat. On two separate occasions, RMR and TEM were measured using indirect calorimetry. VO2max was significantly higher in the swimmers while MAnC was significantly higher in the wrestlers for both the arms and the legs. RMR adjusted for fat-free weight was not significantly different between groups. The differences in total and percentage of TEM between the groups were not statistically significant, and there were no differences in baseline thyroid hormones. These data suggest that despite significant differences in VO2max and WAnT values following long-term aerobic and anaerobic exercise training, resting energy expenditure does not differ between these college athletes. PMID- 7874151 TI - Postexercise energy expenditure in response to acute aerobic or resistive exercise. AB - Postexercise energy metabolism was examined in male subjects age 22-35 years in response to three different treatments: a strenuous bout of resistive exercise (REx), a bout of stationary cycling (AEx) at 50% peak VO2, and a control condition (C) of quiet sitting. Resting metabolic rate (RMR) was measured the morning of and the morning following each condition. Recovery oxygen consumption (RcO2) was measured for 5 hr following each treatment. Total 5-hr RcO2 was higher for the REx treatment relative to both AEx and C, with the largest treatment differences occurring early during recovery. There were no large treatment differences in postexercise respiratory exchange ratio values, except for the first hour of recovery following REx. RMR measured 14.5 hr postexercise for the REx condition was significantly elevated compared to C. These results suggest that strenuous resistive exercise results in a greater excess postexercise oxygen consumption compared to steady-state endurance exercise of similar estimated energy cost. PMID- 7874152 TI - Plasma glucose levels after prolonged strenuous exercise correlate inversely with glycemic response to food consumed before exercise. AB - It was hypothesized that slowly digested carbohydrates, that is, low glycemic index (GI) foods, eaten before prolonged strenuous exercise would increase the blood glucose concentration toward the end of exercise. Six trained cyclists pedaled on a cycle ergometer at 65-70% VO2max 60 min after ingestion of each of four test meals: a low-GI and a high-GI powdered food and a low-GI and a high-GI breakfast cereal, all providing 1 g of available carbohydrate per kilogram of body mass. Plasma glucose levels after more that 90 min of exercise were found to correlate inversely with the observed GI of the foods (p < .01). Free fatty acid levels during the last hour of exercise also correlated inversely with the GI (p < .05). The findings suggest that the slow digestion of carbohydrate in the prevent food favors higher concentrations of fuels in the blood toward the end of exercise. PMID- 7874153 TI - Comparison between carbohydrate feedings before and during exercise on running performance during a 30-km treadmill time trial. AB - The purpose of this study was to compare the effects of a carbohydrate electrolyte solution, ingested during exercise, with the effects of a preexercise carbohydrate meal on endurance running performance. Ten endurance-trained males completed two 30-km treadmill runs. In one trial subjects consumed a placebo solution 4 hr before exercise and a carbohydrate-electrolyte solution immediately before exercise and every 5 km (C). In the other trial, subjects consumed a 4-hr preexercise high-carbohydrate meal and water immediately before exercise and every 5 km (M). Performance times were identical for M and C, and there was no difference in the self-selected speeds. Oxygen uptake, heart rates, perceived rate of exertion, and respiratory exchange ratios were also similar. However, blood glucose concentration was higher in C during the first 20 km of the 30-km run. In M, blood glucose concentration was maintained above 4.5 mmol.L-1 throughout exercise. Thus, the two conditions produced the same 30-km treadmill running performance time. PMID- 7874154 TI - Dietary supplementation and improved anaerobic performance. AB - In the present study, the effects of an increased daily dose of a dietary supplement (ATP-E, 0.2 g.kg-1.day-1) on Wingate test performance were examined in 12 men (21 +/- 1.6 years) prior to and following 14 days of supplement and placebo ingestion. A double-blind and counterbalanced design was used. Results revealed higher (p < .007) preexercise blood ATP (95.4 +/- 10.5 mumol.dl-1) for the entire group following 14 days of ATP-E ingestion compared to placebo measures (87.6 +/- 10.9 mumol.dl-1). Mean power (667 +/- 73 W) was higher (p < .008) after 14 days of ATP-E ingestion versus placebo (619 +/- 67 W). Peak plasma lactate was lower (p < .07) after 14 days of ATP-E ingestion (14.9 +/- 2.8 mmol.L 1) compared to placebo (16.3 +/- 1.6 mmol.L-1). These data suggested that the improvement in 30-s Wingate test performance in this group may be related to the increased dose of ATP-E. PMID- 7874155 TI - Supplementation patterns of competitive male and female bodybuilders. AB - This study described the prevalence of supplement use by 309 male and female competitive bodybuilders. Participants completed a comprehensive survey detailing their supplementation patterns with respect to frequency of product use, spending characteristics, and reasons for use. Supplement use varied with training phase. Protein powder was more popular in the bulking phase, amino acids and fat burners in the cutting phase. Fifty-nine percent of respondents spent $25-100 per month; 4.9% spent over $150. The most popular reason for supplement use was "to meet extra demands of heavy training." In the bulking phase, both weight gain and anabolic supplements were reportedly consumed more frequently by men than women. In the cutting phase, "fat burners" were reportedly consumed by a greater percentage of females than males. The information provided by this study can help sport nutritionists identify supplements most often consumed by bodybuilders and can aid counselors as they guide bodybuilders towards more healthful nutrition practices. PMID- 7874156 TI - Anastasia and the tools of justice. PMID- 7874157 TI - Co-factor insufficiency in dystonia-parkinsonian syndrome. PMID- 7874158 TI - Manifestations of microphthalmia. PMID- 7874159 TI - Genome linkage scanning: systematic or intelligent? PMID- 7874160 TI - Dynamic mutations hit double figures. PMID- 7874161 TI - Screening for truncated NF1 proteins. PMID- 7874162 TI - Redundant genes? PMID- 7874163 TI - CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. AB - We have identified a novel gene containing CAG repeats and mapped it to chromosome 14q32.1, the genetic locus for Machado-Joseph disease (MJD). In normal individuals the gene contains between 13 and 36 CAG repeats, whereas most of the clinically diagnosed patients and all of the affected members of a family with the clinical and pathological diagnosis of MJD show expansion of the repeat number (from 68-79). Southern blot analyses and genomic cloning demonstrates the existence of related genes. These results raise the possibility that similar abnormalities in related genes may give rise to diseases similar to MJD. PMID- 7874164 TI - Isolation of a GCC repeat showing expansion in FRAXF, a fragile site distal to FRAXA and FRAXE. AB - Three folate-sensitive fragile sites, termed FRAXA, FRAXE and FRAXF, have been identified on the distal end of chromosome Xq. The first two contain expanded, hypermethylated and unstable CGG (or GCC) repeats within CpG islands. We now report the isolation of similar sequences responsible for the third fragile site, FRAXF. A 5-kilobase EcoRI fragment derived from a cosmid coincident with the cytogenetic anomaly detects expanded, methylated and unstable sequences in five individuals who exhibit fragile sites in distal Xq; these individuals have normal repeat lengths at both FRAXA and FRAXE. By sequence analysis, the expanded region contains a GCC repeat. PCR and sequence analysis of chromosomes from the general population indicates that the repeat is polymorphic (6 to 29 triplets), and is stable upon transmission. PMID- 7874165 TI - Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. AB - Hereditary progressive dystonia with marked diurnal fluctuation (HPD) (also known as dopa responsive dystonia) is a dystonia with onset in childhood that shows a marked response without any side effects to levodopa. Recently the gene for dopa responsive dystonia (DRD) was mapped to chromosome 14q. Here we report that GTP cyclohydrolase I is mapped to 14q22.1-q22.2. The identification of four independent mutations of the gene for GTP cyclohydrolase I in patients with HPD, as well as a marked decrease in the enzyme's activity in mononuclear blood cells, confirms that the GTP cyclohydrolase I gene is a causative gene for HPD/DRD. This is the first report of a causative gene for the inherited dystonias. PMID- 7874166 TI - Xq-Yq interchange resulting in supernormal X-linked gene expression in severely retarded males with 46,XYq- karyotype. AB - The critical importance of dosage compensation is underscored by a novel human syndrome ("XYXq syndrome") in which we have detected partial X disomy, demonstrated supernormal gene expression resulting from the absence of X inactivation, and correlated this overexpression with its phenotypic consequences. Studies of three unrelated boys with 46,XYq- karyotypes and anomalous phenotypes (severe mental retardation, generalized hypotonia and microcephaly) show the presence of a small portion of distal Xq on the long arm of the Y derivative. Cells from these boys exhibit twice-normal activity of glucose-6-phosphate dehydrogenase, a representative Xq28 gene product. In all three cases, the presence of Xq DNA on a truncated Y chromosome resulted from an aberrant Xq-Yq interchange occurring in the father's germline. PMID- 7874167 TI - Waardenburg syndrome type 2 caused by mutations in the human microphthalmia (MITF) gene. AB - Waardenburg syndrome type 2 (WS2) is a dominantly inherited syndrome of hearing loss and pigmentary disturbances. We recently mapped a WS2 gene to chromosome 3p12.3-p14.1 and proposed as a candidate gene MITF, the human homologue of the mouse microphthalmia (mi) gene. This encodes a putative basic-helix-loop-helix leucine zipper transcription factor expressed in adult skin and in embryonic retina, otic vesicle and hair follicles. Mice carrying mi mutations show reduced pigmentation of the eyes and coat, and with some alleles, microphthalmia, hearing loss, osteopetrosis and mast cell defects. Here we show that affected individuals in two WS2 families have mutations affecting splice sites in the MITF gene. PMID- 7874168 TI - Molecular basis of mouse microphthalmia (mi) mutations helps explain their developmental and phenotypic consequences. AB - Mutations in the mouse microphthalmia (mi) gene affect the development of a number of cell types including melanocytes, osteoclasts and mast cells. Recently, mutations in the human mi gene (MITF) were found in patients with Waardenburg Syndrome type 2 (WS2), a dominantly inherited syndrome associated with hearing loss and pigmentary disturbances. We have characterized the molecular defects associated with eight murine mi mutations, which vary in both their mode of inheritance and in the cell types they affect. These molecular data, combined with the extensive body of genetic data accumulated for murine mi, shed light on the phenotypic and developmental consequences of mi mutations and offer a mouse model for WS2. PMID- 7874169 TI - A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome. AB - Pfeiffer syndrome (PS) is one of the classic autosomal dominant craniosynostosis syndromes with craniofacial anomalies and characteristic broad thumbs and big toes. We have previously mapped one of the genes for PS to the centromeric region of chromosome 8 by linkage analysis. Here we present evidence that mutations in the fibroblast growth factor receptor-1 (FGFR1) gene, which maps to 8p, cause one form of familial Pfeiffer syndrome. A C to G transversion in exon 5, predicting a proline to arginine substitution in the putative extracellular domain, was identified in all affected members of five unrelated PS families but not in any unaffected individuals. FGFR1 therefore becomes the third fibroblast growth factor receptor to be associated with an autosomal dominant skeletal disorder. PMID- 7874170 TI - Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2. AB - Jackson-Weiss syndrome is an autosomal dominant condition characterized by craniosynostosis, foot anomalies and great phenotypic variability. Recently mutations in fibroblast growth factor receptor 2 (FGFR2) have been found in patients with another craniosynostotic syndrome, Crouzon syndrome. FGFR2 is a member of the tyrosine kinase receptor superfamily, having a high affinity for peptides that signal the transduction pathways for mitogenesis, cellular differentiation and embryogenesis. We now report an FGFR2 mutation in the conserved region of the immunoglobulin IIIc domain in the Jackson-Weiss syndrome family in which the syndrome was originally described. In addition, in four of 12 Crouzon syndrome cases, we identified two new mutations and found two previously described mutations in the same region. PMID- 7874171 TI - Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11. AB - Autosomal dominant ataxias are a genetically heterogeneous group of disorders for which spinocerebellar ataxia (SCA) loci on chromosomes 6p, 12q, 14q and 16q have been reported. We have examined 170 individuals (56 of whom were affected) from a previously unreported ten-generation kindred with a dominant ataxia that is clinically and genetically distinct from those previously mapped. The family has two major branches which both descend from the paternal grandparents of President Abraham Lincoln. Among those examined, 56 individuals have a generally non-life threatening cerebellar ataxia. Disease onset varies from 10-68 years and anticipation is evident. We have mapped this gene, spinocerebellar ataxia type 5 (SCA5), to the centromeric region of chromosome 11. PMID- 7874172 TI - A possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3. AB - In a preliminary genome scan of 47 bipolar disorder families, we detected in one family a lod score of 3.41 at the PFKL locus on chromosome 21q22.3. The lod score is robust to marker allele frequencies, phenocopy rates and age-dependent penetrance, and remains strongly positive with changes in affection status. Fourteen other markers in 21q22.3 were tested on this family, with largely positive lod scores. Five of the other 46 families also show positive, but modest lod scores with PFKL. When all 47 families are analysed together, there is little support for linkage to PFKL under homogeneity or heterogeneity using lod score analysis, but the model-free affected-pedigree-member method yields statistically significant results (p < 0.0003). Our results are consistent with the presence of a gene in 21q22.3 predisposing at least one family to bipolar disorder. PMID- 7874173 TI - Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene. AB - The classic murine muscular dystrophy strain, dy, was first described almost 40 years ago. We have identified the molecular basis of an allele of dy, called dy2J, by detecting a mutation in the laminin alpha 2 chain gene--the first identified mutation in laminin-2. The G to A mutation in a splice site consensus sequence causes abnormal splicing and expression of multiple mRNAs. One mRNA is translated into an alpha 2 polypeptide with a deletion in domain VI. The truncated protein apparently lacks important qualities of the wild type protein and is unable to provide sufficient muscle stability. PMID- 7874175 TI - [Seminal tract reconstruction: 15 years experience]. AB - Azoospermia in two spermiograms, normal FSH and normal testicle size are sufficient for the diagnosis of excretory azoospermia and constitute an indication for surgery. Over the last 15 years, in 642 men an epididymo-vasostomy was performed for inflammatory (51%), inborn (44%) or acquired (5%) epididymal obstruction. In 327 selected cases permeability ranged between 11 to 76% according to the location of the anastomosis and fertility followed in 0-52%. Vaso-vasostomy was done in 724 men. Depending on the time after sterilisation or herniotomy obstruction, permeability ranged between 52% and 92%, fertility between 38% and 74%. Double-layered anastomosis with sealing of the anastomoses by fibrin glue improved the results. Special operations for vas mobilisation and testicle elevation which avoid tension upon the anastomosis are outlined. In four men with long obstructions of the vas, testicle transposition into the inguinal area was performed; three of them had a positive postoperative spermiogram and two of them fathered a child. With increasing duration of obstruction the quality of postoperative spermiograms decreases. Sperm autoantibodies were significantly elevated in only 3% of 531 men, and in most cases normal values were seen after relief of obstruction. Reasons of seminal anastomoses are: defective technique, sperm leak, traction upon the anastomosis, infection and epididymal damage. The frequency with which the operation is performed is the main determinant of the competence of the surgeon and the chances of success. PMID- 7874174 TI - Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation. AB - Defects in the human Ca(2+)-sensing receptor gene have recently been shown to cause familial hypocalciuric hypercalcaemia and neonatal severe hyperparathyroidism. We now demonstrate that a missense mutation (Glu128Ala) in this gene causes familial hypocalcaemia in affected members of one family. Xenopus oocytes expressing the mutant receptor exhibit a larger increase in inositol 1,4,5-triphosphate in response to Ca2+ than oocytes expressing the wild type receptor. We conclude that this extracellular domain mutation increases the receptor's activity at low Ca2+ concentrations, causing hypocalcaemia in patients heterozygous for such a mutation. PMID- 7874176 TI - [Treatment of impotence with suction pumps]. AB - Suction erectors are not a new idea in the range of treatments available for impotence. However, urologists have been interested in them for less than 10 years, although they have been available in the U.S.A. since 1974. We describe the results of a series of 32 patients with a mean age of 54 years treated by a Erecaid Osbon pump. 84% of them suffered from organic impotence. The success rate was 66% with a mean follow-up of 6.6 months. No serious adverse effect was observed. However, minor problems were reported by 75% of users: inhibition of ejaculation, pain, cold or pivoting penis. This is a safe and effective treatment, provided patients are correctly selected, as cases of partial and psychogenic impotence have a much lower success rate: failure rate in the case of organic impotence: 30%, psychogenic: 40%, total: 26%, partial: 56%. The better results are obtained in patients suffering from organic impotence, in a stable couple and whose partners participate in the therapeutic choice. The literature is reviewed and discussed. PMID- 7874177 TI - [Strangulated urethral prolapse in a young woman: a rare urological emergency]. AB - Total prolapse of the urethral mucosa in women is an uncommon lesion, observed at the two extremes of reproductive life. Strangulation of urethral prolapse is a rare complication whose emergency treatment is essentially surgical. The authors report a case of strangulated urethral prolapse in a 43-year-old woman, for which several pathophysiological mechanisms can be proposed: first delivery by forceps, poorly repaired perineal tear, untreated early menopause at the age of 40 years. Urethral prolapse in elderly women has become much less common since the introduction of hormone replacement therapy for menopause. Other physiopathogenic factors may be responsible for this prolapse, such as thrombosis of the juxtameatal submucosal veins, laxity between the mucosa and submucosa or uretrodetrusor dyssynergia. The diagnosis of strangulated urethral prolapse is based on the discovery of a very painful, violaceous, inflammatory circular mucosal tumour surrounding the urethral meatus. If rapid reduction of the prolapse is not obtained with systemic and topical oestrogen therapy, the strangulated mucosal flap must be resected surgically, followed by apposition of the urethral mucosal and submucosal planes. This suture, in tissues which are always inflamed, must be calibrated and the urine must be drained by bladder catheter for about ten days. Meatal stricture is the principal complication of this surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874178 TI - [Subcapsular renal hematoma after extra corporeal lithotripsy: a case report]. AB - A 61-year old man presented with a subcapsular renal hematoma following Extracorporeal Shock Wave Lithotripsy for a renal stone. The authors discuss presenting conditions, risk factors, preventive measures, therapeutic implications and sequellae of such a complication. PMID- 7874179 TI - [Epididymal leiomyosarcoma. A case report with review of the literature]. AB - The authors report the 14th case of leiomyosarcoma of the epididymis in a 67-year old man. Treatment consisted of radical left orchidectomy without adjuvant chemotherapy or radiotherapy. The patient is free of local or distant recurrence with a follow-up of 2 years. The other 13 cases reported in the literature are briefly reviewed. PMID- 7874180 TI - [Laparoscopic radical nephrectomy and ureterectomy in a child. A case report]. AB - The authors report a case of laparoscopic nephroureterectomy in a four year old girl with a small kidney destroyed by vesicoureteric reflux. PMID- 7874181 TI - [Value of three-dimensional surface reconstruction scanning in urology. Preliminary results]. AB - The development of helicoidal CT acquisition allows 3D reconstruction of vessels, cavities or parenchyma of mobile organs such as the kidney. The value of this 3D surface reconstruction was investigated in various areas of urology: congenital malformations (horseshoe kidney, megaureter, ectopic organs), acquired malformations (diverticulum, trabeculated bladder), renal stones, particularly staghorn calculi, and renal transplantation. The fields of interest of 3D CT scans are still poorly defined, but are probably threefold: diagnostic, therapeutic and for teaching purposes. 3D representation completes classical axial scans and, in some cases, competes with other more invasive imaging techniques. PMID- 7874182 TI - [Technique and results of the "Mini-Bricker" urinary tract diversion after total cystectomy for bladder tumors]. AB - The authors have performed a "Mini-Bricker" operation in 24 patients with bladder cancer. This technique consists of urinary diversion in which the size of the intestinal loop is reduced to an average of 4 cm and the ureteroileal anastomosis is performed end-to-end in order to allow subsequent endourological procedures, if necessary. The postoperative course was uneventful in 71% of cases. Seven early complications were reported: 3 infectious, 1 thromboembolic and 2 hernias. In the medium term, one case of disturbances and 2 stenoses of the ureteroileal anastomosis were treated by endoscopic dilatation. The median follow-up is 3 years and 5 patients have died. A retrospective survey of quality of life revealed that 86% of patients were satisfied with their diversion and rapidly acquired autonomy following cystectomy without the need for retraining and without having to get up at night. PMID- 7874183 TI - [Persistence of the bulbocavernosus reflex during micturition in bladder hyperactivity of central neurological origin]. AB - The bulbocavernosus reflex (BCR) was evaluated before, during and after micturition in 35 patients. All the 19 patients with upper motor neuron lesions had a positive BCR during micturition. By comparison, 11/16 of the patients with a lower motor neuron lesion or with urogynecologic diseases did not have a BCR during micturition. The persistence of BCR during voiding seems to be a loss of central inhibition and maybe represent a good sign of upper motor neuron bladder dysfunction. PMID- 7874184 TI - [Value of radiologic examinations in the diagnosis and staging of upper urinary tract tumors]. AB - From 1980 to 1991, 109 patients were treated for a tumour of the upper urinary tract. All patients were examined by intravenous urography (IVU) which had a sensitivity of 61%. The combination of IVU + RUP established the diagnosis in 72% of cases. Renal ultrasonography and abdominal computed tomography (CT) were performed in 41 and 67 cases, respectively. The sensitivity of ultrasonography was 40% and that of CT was 72%. CT was more sensitive for tumours of the renal pelvis (78%) than for ureteric tumours (53%) (p < 0.02) and when the tumour diameter exceeded 2 cm (70% vs 45%: p < 0.01). The sensitivity of CT for lymph node extension was 47% with an accuracy of 88%. Preoperative CT staging was compared to pathological staging: CT staging had an accuracy of 56%; in 31% of cases, CT underestimated the parietal extension of the tumour. The sensitivity of CT to assess invasion of the renal parenchyma and of the perirenal fat was 52% and 74%, respectively (p < 0.01). Morphological examinations are able to diagnose a tumour of the upper urinary tract in 3 out of 4 cases. Correct preoperative staging can only be achieved on one half of cases, which constitutes a drawback to the development of conservative treatment techniques. PMID- 7874185 TI - [Treatment of stress urinary incontinence by the Raz vaginal colpopexy]. AB - In this study we present our experience from the application of the bladder neck suspension as modified by Raz on 37 patients. All patients had severe genuine stress incontinence. Twenty of them had undergone previous surgery for the same problem, and 16 patients had had a previous hysterectomy. In addition 15 patients had a small cystocele. In all cases, the Raz procedure was performed by the same surgical team. The follow-up ranged from 8-32 months (mean follow-up 15.4). The overall success rate was 86.5%. Patients with no history of previous surgery and all patients with cystocele were cured. The 5 failures occurred in patients with previous surgery and hysterectomy. The complications were few. It is concluded that the Raz bladder neck suspension is a safe and effective method for the treatment of stress incontinence, especially in cases with cystocele or failure after primary treatment. PMID- 7874186 TI - [Tubulo-papillary tumors of the kidney. Clinical, histologic and cytogenetic aspects. 15 new cases]. AB - Between 1987 and 1992, we operated on 15 patients with tubulopapillary tumours (TPT) of the kidney, corresponding to 10% of all renal cancers operated during this 5-year period, which brings the total number of published cases to 418. TPT differ from non-tubulopapillary tumours in several ways. The medical imaging findings may differ when the tumour is not necrotic (20 to 30% of cases). The histology differs not only in terms of the tumour architecture, but also by the frequent association (9/15 cases) with other ipsilateral or contralateral renal anomalies: 2 bilateral tumours, 3 tumours associated with multiple cysts and 4 multifocal tumours. These characteristics, combined with the finding of 12 familial cases suggest a genetic origin for TPT, especially as the genetic abnormalities detected (tri-or tetrasomy 17) differ from the anomalies usually detected in non-tubulopapillary tumours (anomalies of 3p and 5q). This study is the first to report familial cases of TPT. The prognosis of these tumours, generally better than that of non-tubulopapillary tumours, suggests the possibility of conservative surgery when the diagnosis can be established preoperative or at operation. PMID- 7874187 TI - [Stage M1b prostatic adenocarcinoma: prognostic factors, value of bone scintigraphy]. AB - Based on a retrospective study of 52 patients with prostatic adenocarcinoma and bone metastases (stage M1b), the authors analysed the following prognostic factors at the time of diagnosis: age, general status, bone pain, haemoglobin, local tumour volume, ureteric repercussions, pre and post-treatment PAP and PSA levels, Gleason score, and metastatic spread on bone scan. This study demonstrated two predominant prognostic factors for the appearance of early or late therapeutic escape: tumour differentiation established by the Gleason score (P = 0.003), stage of the disease, i.e. local tumour volume (p = 0.001) and bone mass invaded on bone scan (p = 0.0002). The other prognostic factors can be deduced from these two parameters. Qualitative analysis of the initial bone scan allowed patients with peripheral bone metastases to be distinguished from those with exclusively axial involvement. The two-year survival was 50% in patients with peripheral metastases versus 93% in patients without peripheral metastases (p < 0.05). Although bone metastasis constitutes a decisive prognostic factor, the detection of peripheral bone metastases appears to be a factor of poor prognosis. PMID- 7874188 TI - Endocrine management of breast cancer. AB - Hormonal therapy for breast cancer began more than a century ago with the observation that bilateral oophorectomy caused tumor regression in selected premenopausal patients. In the first half of this century, besides extending ablation of ovarian function to photon irradiation, surgical adrenalectomy and hyophysectomy were introduced, and hormonal additive therapy was established. Regression rates for advanced breast cancer with all types of endocrine therapy at this point did not exceed 35%. The demonstration that adjuvant systemic therapy can prolong the disease-free interval and improve overall survival has been a major advance in the management of breast cancer, the rationale was to control or eliminate micrometastases before tumor recurrence. The nonsteroidal antiestrogen tamoxifen was chosen for the majority of studies since the mid 1970s. Since the first report of successful treatment of metastatic breast cancer, the number of treated women worldwide has reached over 3,000,000. Objective response rate (CR+PR following UICC) in unselected patients is 34%. Tamoxifen has been used successfully to treat both pre- and postmenopausal women with all stages of the disease. In an overview analysis of 30,000 patients from 40 trials of adjuvant tamoxifen, a significant increase was found in both disease free and overall survival. When patients were separated by nodal status, statistically significant increases were observed in disease-free and overall survival for both node-positive and node-negative patients. Women over 50 appear to benefit most from tamoxifen treatment experiencing highly significant increases in disease-free and overall survival regardless of nodal status. However, since tamoxifen primarily acts as a cytostatic and not cytotoxic agent, most patients ultimately experience disease recurrence or progression during or after therapy. Newer antiestrogens include trioxifene, toremifene, and droloxifene (3-OH-tamoxifen). Randomized, prospective studies are still under way to establish their clinical superiority (or lack of it). Progestins exert direct antiproliferative effects on human breast cancer cell lines. They may also exert direct antiestrogenic action by increasing the oxidative activity of 17 beta hydroxy-steroid-dehydrogenase, thereby facilitating the conversion of estradiol to estrone. Progestins may exert additional antiestrogenic effects by suppressing estrogen receptor levels. As they also cause estrogen deprivation indirectly through suppression of pituitary ACTH secretion, resulting in reduced production of adrenal androgen precursors, both low- and high-dose regimens have been studied. Aromatase inhibition in premenopausal women interrupts estrogen biosynthesis; the reflex rise in FSH then stimulates production of new aromatase enzyme, and the LH increment results in enhanced ovarian steroidogenesis, counteracting the inhibitory action of aromatase-blocking drugs on the ovary.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7874189 TI - Breast cancer risk and hormone replacement therapy: a review of the epidemiology. AB - Hormone-related cancers account for more than 20% of all newly diagnosed malignancies and more than 40% of all female cancers in the United States. The life-time odds of getting breast cancer in North America are now one in eight. Mortality rates have held almost steady over the past 20 years, even though the number of new cases has grown. The impact of exogenous hormones on risk of reproductive cancer, especially breast cancer, has been the focus of considerable interest in recent years as the use of exogenous hormones (both pre-menopausally and post-menopausally) has increased. Evidence concerning the effect of hormone replacement therapy (HRT) on breast cancer risk is presented. The epidemiology of other risk factors for breast cancer is summarized as background; this includes reproductive factors (such as age at first birth, and age at menarche and menopause), family history, and use of exogenous hormones other than HRT. PMID- 7874190 TI - Aromatase gene expression in adipose tissue: relationship to breast cancer. AB - Extraglandular conversion of C19 steroids to estrogens takes place primarily in the stromal cell component of adipose tissue and is catalyzed by aromatase cytochrome P450 (P450arom; the product of the CYP19 gene). CYP19 gene expression and aromatase activity in breast adipose stromal cells in culture are subject to complex hormonal regulation, which was recently found to be mediated in part by alternative use of tissue-specific promoters of the CYP19 gene. It has been proposed that increased local aromatase activity in breast adipose tissue may influence the growth of breast carcinomas. Using competitive RT-PCR, we quantified P450arom transcripts in breast adipose tissue from mastectomy specimens. In 10/15 patients, highest transcript levels were found in the quadrant where the tumor was located. We also found the highest proportions of adipose stromal cells versus adipocytes in those quadrants. Such findings suggest that regional differences in the relative proportions of the various histologic components give rise to locally elevated concentrations of estrogens. Although the initiating events are not known, once a neoplastic change has occurred, tumor growth may be promoted by the locally increased estrogen levels. We are currently investigating alternative promoter use for CYP19 gene transcription to explain this association. Our results underscore the importance of aromatase inhibitors as effective agents in treatment of hormone-responsive breast cancer, since aromatase inhibitors reduce local aromatase activity as well as blood estradiol levels. PMID- 7874191 TI - The endometrium: effects of estrogen and estrogen-progestogen replacement therapy. AB - A large bulk of data link the use of unopposed estrogens to an increased risk of endometrial cancer. Cancers associated with estrogen use are often well differentiated and carry a good prognosis. Concomitant use of progestogens either cyclically or continuously substantially reduces the risk of promoting endometrial cancer. The development of endometrial cancers as a result of prolonged estrogen medication often occurs via hyperplasia (and atypical hyperplasia). The reason for this increase is not known in detail, but estrogens are believed to be promoter substances by increasing miotic activity and possibly also by down-regulating the defense system against abnormal cell clones. Estrogen receptor activity seems to be dependent on the degree of phosphorylation. Receptor interaction with the specific sites upstream of "regulatory genes" may regulate a variety of steps in gene expression from transcription and mRNA half life to protein processing, permitting a rapid regulation of the nuclear protooncogenes. This may also explain why serum placental protein reflects endometrial status during hormone replacement therapy. Both 17 beta-estradiol and medroxyprogesterone acetate are capable of modulating DNA synthesis in the endometrial glandular epithelium. The endothelin receptor type A seems to be stimulated during the proliferative phase, whereas an increase in the endothelin B type receptor has been noted in secretory and menstrual phases. Furthermore, low doses of oral norethisterone and levonorgestrel induce morphological changes inclusive of breaks in the endothelial lining of veins with and without hemostatic plugs. Endometrial fibrinolytic enzymes seem to be modulated by estrogens and progestogens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874192 TI - Cancer surveillance during HRT. AB - The principal cancer sites in women are the following in order of frequency: breast, colorectal, lung, uterus and ovary. Thus, all women during the climacterium have a potential risk of developing any of these cancers. This implies that appropriate means for prevention and early diagnosis must be established. Results from trials studying the association between hormone replacement therapy (HRT) and breast cancer are not conclusive. There is some evidence of a minimal increased cancer induction risk when using high and long term HRT dosages, though we must await further studies combining different kinds, dosages and routes of administration of the hormones which are currently being prescribed. Breast surveillance must include medical history, physical examination, an annual mammography, as well as follow-up of all previously detected breast pathology through both physical examination and mammography. One should bear in mind that HRT may increase breast parenchymal density and lower mammography sensitivity. HRT seems to protect against colorectal cancer. However, because of the high frequency of this disease among women over 50 years of age, an annual stool test for occult blood should be performed. Endometrial cancer risk is much increased after HRT administration, still persisting after estrogen wash-out. This risk can be prevented by giving an opposed progestogen. Some diagnostic assessments, especially echography and endometrial biopsy, are recommended in certain cases such as patients with metrorrhagia or with a history of suspected cancer. There do not seem to be any demonstrated adverse effects on ovary and cervix due to HRT, although an annual Pap smear for cervical cancer screening is currently recommended.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874193 TI - Hormone replacement therapy and estrogen-dependent cancers. AB - Until a few years ago, every treated breast cancer was an absolute contraindication to hormonal replacement therapy (HRT). However, the very high five-year survival rate in stage I breast cancer observed today brings more and more apparently healthy early postmenopausal women who have been treated for breast cancer in the past and who are suffering from heavy vasomotor symptoms due to estrogen deficiency to gynecological consultation. Usually well informed, the same group of women starts to worry about an increased risk of postmenopausal osteoporosis and of cardiovascular diseases. What attitude should be adopted today? Our approach should be differentiated and respect the staging, the estrogen-receptor status, and the presence or absence of axillary lymph-node metastasis of every patient. In estrogen receptor-negative women, there is no contraindication to continuous combined HRT by a fixed estrogen-progestin combination. In estrogen receptor-positive and lymph-node-negative patients, treatment by a nonaromatizable progestin, such as medrogestone or medroxyprogesterone acetate (MPA), can be introduced to relieve the patient from her postmenopausal syndrome. After 2-3 years of a favorable evolution of the treated cancer, the substitution might be shifted to a fixed-combined continuous HRT. Because estrogen receptor-positive and lymph-node-positive patients today are usually receiving adjuvant treatment with tamoxifen, they profit already from prophylaxis for postmenopausal osteoporosis and, very likely, from decreased cardiovascular risk. If women out of this group continue to suffer from heavy vasomotor symptoms, MPA might be added. However, it must be stressed that every administration of sexual steroids to women who have been treated for breast cancer has to be started only in full agreement with the treating oncologist concerned with the case and only after having obtained the informed consent of the patient. The new ethical dilemma will be our attitude to quality of life in relation to life prolongation. PMID- 7874194 TI - Sensory components controlling bacterial nitrogen assimilation. AB - In enteric bacteria, the transcription of the Ntr regulon is regulated by a signal transduction system that measures and transmits information on the nitrogen status of the cell. Four of the components of this signal transduction apparatus have been previously identified, and the roles of these are known, to a first approximation, from studies with purified components. The sensor is a uridylyltransferase/uridylyl-removing enzyme (UTase/UR) that controls the uridylylation state of the PII protein. PII indirectly regulates the transcription of the Ntr regulon by acting through the kinase/phosphatase protein NRII. In the absence of unmodified PII, NRII autophosphorylates on a histidine residue, and these phosphoryl groups are transferred to the transcription factor NRI, resulting in the conversion of NRI to the form able to activate transcription. In the presence of PII and NRII, NRI approximately P is rapidly dephosphorylated, preventing the activation of Ntr transcription. This PII dependent dephosphorylation of NRI approximately P is referred to as the regulated phosphatase activity. In this report, we describe improved methods for the purification of the UTase/UR and PII, and the crystallization of PII. We also present improved methods for the assay of the activities of the UTase/UR protein and PII. The results of our assays indicate that purified PII is effective in eliciting the regulated phosphatase activity, but does not affect the autophosphorylation of NRII or affect the transfer of phosphoryl groups from NRII approximately P to NRI. In addition, we demonstrate that the elicitation of the regulated phosphatase activity by PII is strongly dependent on the ratio of NRI approximately P to NRI, and that the isolated N-terminal domain of NRI, once phosphorylated, is dephosphorylated by the regulated phosphatase activity. PMID- 7874195 TI - DNA-related conditions controlling the initiation of sporulation in Bacillus subtilis. AB - In the Gram-positive bacterium Bacillus subtilis, the developmental process of spore formation occurs in response to nutrient deprivation and requires the generation of two different cell types with distinct programs of gene expression. Entry into sporulation is regulated primarily by activation (phosphorylation) of the transcription factor encoded by spo0A. The phosphorylation state of Spo0A is controlled by a multi-component phospho-transfer pathway and by at least one phosphatase. Recent experiments indicate that several intracellular conditions that decrease the fidelity of chromosome transmission inhibit production of Spo0A approximately P. These conditions include inhibition of DNA replication, DNA damage, and some alterations in the chromosome partitioning and cell division machinery. Coupling accumulation of a critical level of Spo0A approximately P to these conditions seems to serve as a developmental checkpoint to ensure that cells do not attempt to sporulate unless they are able to provide an intact, undamaged chromosome for each of the two cell types needed for sporulation. PMID- 7874196 TI - The control of spatial organization during cellular differentiation. AB - Caulobacter crescentus is a dimorphic bacterium that yields two distinct cell types with every cell division, a motile swarmer cell and a sessile stalked cell. Caulobacter, therefore, possesses a simple developmental program and is used as an model system to determine basic mechanisms of cellular morphogenesis. The generation of the asymmetric predivisional cell requires the temporal expression of many genes as well as the precise intracellular positioning of these gene products. Analysis of the biogenesis and positioning of cell type-specific genes and proteins has been instrumental in understanding the underlying principles as to how asymmetry in the predivisional cell is generated. This manuscript explores our current understanding of the mechanisms by which Caulobacter differentiation is achieved. PMID- 7874197 TI - Regulation of yeast chromosome segregation by Ipl1 protein kinase and type 1 protein phosphatase. AB - Chromosome segregation is a complicated process that involves the coordinated functioning of a large number of cellular components. In this process, many proteins are activated and inactivated in a strict temporal order. While much progress has been made recently in the identification of structural components that are involved in chromosome segregation, relatively little is known about their regulation. We have investigated the chromosome segregation process in the budding yeast Saccharomyces cerevisiae. Our results indicate that this process absolutely requires a functional Ipl1 protein kinase. Upon inactivation of this protein kinase, yeast cells missegregate chromosomes severely and die within a single cell cycle. Furthermore, the inviability caused by a partial reduction in Ipl1 function can be rescued by perturbations that reduce type 1 protein phosphatase activity, thus suggesting that type 1 protein phosphatase acts in opposition to the Ipl1 protein kinase to insure the high fidelity of chromosome segregation in yeast cells. The purpose of this article is to describe some of our ongoing efforts to characterize Ipl1 and PP1 functions. PMID- 7874198 TI - Role of tyrosine phosphorylation-dephosphorylation in copy number control of the yeast plasmid 2 micron circle. AB - A key feature of the copy control in the 2 micron circle plasmid of Saccharomyces cerevisiae is its ability to amplify when the copy number drops below the steady state value. The Flp protein encoded by the plasmid is an essential component of the amplification mechanism. A central regulatory event in amplification involves the phosphorylation/dephosphorylation of Tyr-343 of Flp. Tyrosine phosphorylation is achieved by a transesterification mechanism involving a specific phosphodiester within the 2 micron circle. The dephosphorylation is also a transesterification reaction that uses a specific 5'-OH (generated during tyrosine phosphorylation) as the phosphoryl acceptor. A sum of four phosphorylation/dephosphorylation reactions, coordinated in sets of two, is thought to invert the relative directions of a pair of replication forks. This allows more than one copy of the plasmid to be made from a single replication initiation event. In this paper we discuss the structural features of the Flp active site that control and coordinate the transesterification reactions required for amplification. PMID- 7874200 TI - Dissecting the protein kinase C/MAP kinase signalling pathway of Saccharomyces cerevisiae. AB - The PKC1 gene of the budding yeast Saccharomyces cerevisiae encodes a homolog of the alpha, beta, and gamma isoforms of mammalian PKC that is essential for cell growth. Loss of PKC1 function results in a cell lysis defect that is suppressed by osmotic stabilizing agents, suggesting a defect in cell wall integrity. In this study, we show that Pkc1p-depleted cells develop holes in their cell walls positioned at their bud tips, the site to which growth is focused during polarized cell growth. This result suggests that pkc1 mutants are deficient in the process of cell wall remodeling during growth. In further support of this model, cells bearing a pkc1 delta mutation, allowed to proliferate in the presence of osmotic stabilizing agents, possessed cell walls that were only 60% as thick as wild-type cell walls. This diminution in cell wall material affected both the beta-glucan layer and the mannoprotein layer. We have exploited the cell lysis defect of pkc1 mutants to identify genes that function within the same signalling pathway at points downstream of PKC1. These genes comprise a protein kinase cascade that culminates in the activation of the MAP kinase homolog Mpk1p. The proposed order of protein kinase function, based on genetic experiments, is Pkc1p to Bck1p to Mkk1/2p to Mpk1p. Consistent with the proposed model, Pkc1p selectively phosphorylates Bck1p in vitro and Mpk1p protein kinase activity requires a functional BCK1 gene. PMID- 7874199 TI - The yeast pheromone response pathway: new insights into signal transmission. AB - The yeast (Saccharomyces cerevisiae) pheromone response pathway is one of the best understood eukaryotic signal transduction pathways. Nonetheless, it is likely that components and regulators of the pathway remain to be identified. We have employed three approaches to learn about interactions among known pathway components and to identify new components. First, the two-hybrid system of Fields and Song revealed that STE5, a protein of unknown biochemical function, interacts with each member of the MAP kinase cascade. One interpretation of this finding is that STE5 facilitates interactions between members of the cascade and thereby makes signal transmission more efficient. Second, genetic studies have identified new gene functions that appear to be involved in pheromone response. One of these is homologous to RHO-GAP proteins, an observation that suggests that a RHO protein (members of the RAS super-family) is part of the response pathway. A second gene function, FAR3, appears to be required only for a specific facet of pheromone response, arrest of the mitotic cell division cycle in G1. PMID- 7874201 TI - Cellular function of protein phosphatase 2C in yeast. AB - Protein phosphatase 2C (PP2C) is one of four major classes of protein serine/threonine-phosphatases, which requires Mg2+ for its activity. PP2C activity distributes ubiquitously among eukaryotes and enzymes purified from mammalian tissues were well characterized biochemically, however, very little is known about their biological function. We have been trying to identify cellular function of PP2C by genetic analyses in fission yeast Schizosaccharomyces pombe. So far, three PP2C homologs, ptc1+, ptc2+, and ptc3+, have been cloned and their activity were detected in the S. pombe cell lysates. Experiments using ptc mutants constructed by gene disruption technique have revealed the involvement of PP2C in the heat shock response and possibly osmoregulation in yeast cells. PMID- 7874202 TI - Resolving the sevenless pathway using sensitized genetic backgrounds. PMID- 7874203 TI - Regulation of the MAP kinase cascade. AB - The MAP kinase cascade is regulated by many hormones and growth factors and its activation leads to changes in properties of cytoplasmic, membrane-associated, and nuclear proteins. The MAP kinases themselves are activated by MEKS. MEKs lie at a point of convergence for multiple upstream signals, mediated by distinct protein kinases, Raf, MEK kinase, and Mos, all of which have MEK kinase activity. Additional inputs that stimulate the MAP kinase pathway are the activation of protein kinase C and the yeast protein kinase STE20. Mechanisms of regulation of some of the upstream components of this cascade have not yet been fully elucidated. PMID- 7874204 TI - Bibliography of cellular and molecular biology research. PMID- 7874205 TI - Inquiring minds want to know. PMID- 7874206 TI - Accurate assessment of ventilation and oxygenation. AB - Monitoring pulmonary function with an effective nursing assessment can identify patient problems early. An understanding of ventilation, alveolar perfusion, oxygenation, and patient signs and symptoms, guides medical-surgical nurses in assessment and in intervention choices. PMID- 7874207 TI - Recognizing the patient at risk for opportunistic infections. AB - Advances in the treatment of many chronic and end-stage diseases as well as the emergence of AIDS has yielded an immunocompromised patient population. Nurses caring for these patients must be aware of their potential for developing deadly opportunistic infections. By identifying the patient at risk, nurses hope to delay or prevent the development of these diseases. PMID- 7874208 TI - Stroke and heart attack prevention education. AB - Nurses should assume a more active role in developing effective preventative health care programs. A successful, cost-effective collaborative approach to heart and stroke education has been developed that all nurses can use in a variety of settings. PMID- 7874209 TI - Managing pain in a diverse medical-surgical patient population. AB - A joint research and quality assurance task force was established to evaluate pain management practices. Medical and surgical patients and their nurses were surveyed about patient pain during the hospitalization and a plan for pain assessment and management was developed. PMID- 7874210 TI - Fatigue and nutrition. AB - Fatigue is a significant clinical problem for medical-surgical patients experiencing acute and chronic health problems. Fatigue can cause nutritional intake to suffer and compromises overall functional status. A thorough assessment of the factors associated with a patient's fatigue enables the nurse to develop a fatigue management plan and implement other strategies to minimize the negative consequences of fatigue. PMID- 7874211 TI - Contemporary management techniques. PMID- 7874212 TI - Treatment algorithm for hypertension. PMID- 7874213 TI - Stuck between a rock and a hard place. PMID- 7874214 TI - Where are the leaders among us? PMID- 7874215 TI - Subacute care: nursing for the next century. PMID- 7874216 TI - Managing constipation using a research-based protocol. AB - Constipation, a common health problem particularly for elderly and hospitalized patients, can cause abdominal pain, discomfort, gas, headaches, nausea, anorexia, a bad taste in the mouth, and potentially adds to functional loss and length of stay. As part of a quality improvement initiative, a research-based interdisciplinary protocol was developed to prevent constipation in hospitalized immobile vascular surgery patients. Using a combination of dietary fiber, increased fluid, and hygiene measures over a 3-year period, incidence of constipation was reduced from 59% to about 9%. The incidence of impaction was eliminated and requests for laxatives and enemas were reduced from 59% to about 8%. PMID- 7874217 TI - Domestic violence: recognition, intervention, and prevention. AB - Domestic violence is a significant social and health problem that has received intensive recent publicity in the lay media. Nurses should play a major role in primary, secondary, and tertiary prevention interventions. Intensified health promotion and public policy initiatives can reduce the incidence of domestic violence in the future. PMID- 7874218 TI - Determining nasoenteral feeding tube placement. AB - Tube feedings have been a common nutritional support technique for decades. Enteral nutrition is safer, easier, and less costly than the alternative, parenteral nutrition. Problems do occur, such as pulmonary complications. In this review, techniques to determine the placement of nasoenteral feeding tubes are evaluated, and implications for research and practice are discussed. PMID- 7874219 TI - The effectiveness of a hospital bedside computer system. AB - A hospital implemented a computerized documentation system using planned change. Nursing staff and managers were instrumental in reviewing and choosing a system, and implementing and evaluating project results. The project was successful and raised some critical ethical and legal issues. PMID- 7874220 TI - Determining ICU visiting hours. AB - Visiting hours play an integral role in the intensive care unit (ICU) for both patients and health care providers. Family members offer support and comfort to patients during critical illnesses. Nurses, however, often view visiting hours as intrusive and time consuming. The issue of restricted versus open visiting hours continues in many ICUs, and the advantages and disadvantages of both types of visitation must be weighed before selecting the visiting hours appropriate for the institution. PMID- 7874221 TI - Unrecognized depression in the elderly: a nursing assessment challenge. AB - Depression in the elderly has been widely underdiagnosed and undertreated. Geriatric depression has a unique presentation that differs from the hallmarks of depressive illness documented in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) (American Psychiatric Association, 1994). The "masked" presentation of depression in the elderly contributes to problems with accurate assessment, prompt diagnosis, and treatment. Without treatment, there are serious negative consequences for elderly clients such as cognitive impairment, physical disability, social isolation, and suicide. Enhancing professional nurses' awareness of this underrecognized mental health problem among elderly patients is a significant priority. PMID- 7874222 TI - What does an ethics consultant do? PMID- 7874223 TI - Medical and retirement benefit options for a changing employment environment. PMID- 7874224 TI - Understanding ACE inhibitors. PMID- 7874225 TI - Changing visiting practices in critical care units. PMID- 7874226 TI - Culture and the nurse-patient dyad. PMID- 7874227 TI - Creating our future. PMID- 7874228 TI - Beeper technology: improving staff efficiency and decreasing noise levels on medical-surgical units. PMID- 7874229 TI - Students in partnership. PMID- 7874230 TI - Continuing down the road much traveled: health care and the Republican-dominated 104th Congress. PMID- 7874231 TI - Hippocampal mossy cell function: a speculative view. PMID- 7874232 TI - Non-lamellar propagation of entorhinal influences in the hippocampal formation: multiple electrode recordings in the isolated guinea pig brain in vitro. AB - Experiments were carried out to study the spatiotemporal organization of medial entorhinal inputs to the hippocampal system. They were performed in the isolated guinea pig brain in vitro preparation as it provides easy access to the medial entorhinal cortex (mEC) which is difficult to reach in vivo. Multiple simultaneous field potential recordings along the septotemporal extent of the dentate granular layer revealed that the mEC projection to the dentate gyrus (DG) is organized topographically. Thus, stimulation of the caudal regions of the mEC elicited population spikes (PSs) in the septal pole of the DG while successively more rostral stimulation sites activated progressively more temporal sectors of the DG. However, threshold mEC stimuli never elicited PSs over more than one third of the DG. In the CA1 pyramidal layer, only trisynaptic PSs were evoked by the mEC stimulation (latency > 20 ms at 30 degrees C). However, PSs were widely distributed in the transverse and longitudinal axes of the hippocampus and, irrespective of the mEC stimulation site, the latency of CA1 PSs gradually increased from the CA3/CA1 border toward the subiculum. By contrast, in the longitudinal axis, each segment of the CA1 region responded at a shorter latency to stimulation of a given rostrocaudal level of the mEC. Septal CA1 levels responded at shorter latencies to caudal mEC stimulation sites while more temporal CA1 levels responded at shorter latencies to rostral mEC stimulation sites. When stimulated at threshold stimulation intensity, the initial CA1 response propagated to the rest of the CA1 field with a conduction velocity of 0.5-0.9 m/s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874233 TI - Spatial information content and reliability of hippocampal CA1 neurons: effects of visual input. AB - The effects of darkness on quantitative spatial firing characteristics of 235 hippocampal CA1 "complex spike" (CS) cells were studied in young and old Fischer 344 rats during food-motivated performance of a randomized, forced-choice task on an eight-arm radial maze. The room lights were turned on or off on alternate blocks of all eight arms. In the dark, a lower proportion of CS cells had "place fields," and the fields were less specific and less reliable than in the light. A small number of cells had place fields unique to the dark condition. Like CS cells, Theta cells showed a reduction in spatially related firing in the dark. The specificity and reliability of the place fields under both light and dark conditions were similar for both age groups. Increasing the salience of the environment, by increasing the light level and the number of visual cues in the light condition, did not affect the specificity or reliability of the place fields. Even though all rats had substantial prior experience with the environment, and were placed on the maze center under normal illumination before the first dark trial, the correlation between the firing pattern in the light and dark increased after the rat first traversed the maze in the light. Thus, even after considerable experience with the environment over days, experiencing the illuminated environment from different locations on a given day was a significant factor affecting subsequent location and reliability of place fields in darkness. While the task was simple and errors rare, rats that made fewer errors (i.e., re entries into the previously visited arm) also had more reliable place cells, but no such correlation was found with place cell specificity. Thus, the reliability of spatial firing in the hippocampus may be more important for spatial navigation than the size of the place fields per se. Alternatively, both spatial memory and place field reliability may be modulated by a common variable, such as attention. PMID- 7874234 TI - Ipsilateral associational pathway in the dentate gyrus: an excitatory feedback system that supports N-methyl-D-aspartate-dependent long-term potentiation. AB - Axons from granule cells in the dentate gyrus of the rat hippocampus project to cells in the hilar region, including mossy cells, which project along the longitudinal axis of the hippocampus and synapse in the inner (proximal) one third of the molecular layer of the dentate gyrus. To study this feedback system, multiple recording electrodes were located along the longitudinal (septo temporal) axis in the dorsal leaf of the dentate gyrus in urethane-anesthetized rats. Single pulse electrical stimuli delivered to the hilar region evoked negative-going, monosynaptic field potentials that were largest in the inner one third of the molecular layer (commissural zone). These evoked field potentials (EFPs) were recorded simultaneously at three to five locations. The latency to onset and peak amplitude of the EFP varied linearly with distance from point of stimulation, and EFPs were elicited in both directions along the longitudinal axis. The transmission speed was estimated to be 1.4 m/s. Tetanic stimulation of the hilar region potentiated the EFP slopes (mean = 26%). Potentiation lasted at least 2 hours and was specific to responses from the tetanized stimulating electrode; the responses to other stimulating electrodes in the hilus and the angular bundle of the perforant path changed less than 4%. Combined stimulation of the hilus and the medial perforant path increased the magnitude of recorded field potentials and population spikes, demonstrating that both pathways are excitatory. NMDA antagonist NPC-17742 blocked potentiation of EFP slopes in both the medial perforant path and hilus pathways. The results suggest that the ipsilateral associational system of the dentate gyrus is excitatory and capable of supporting long-lasting NMDA-dependent, synapse-specific plasticity. PMID- 7874235 TI - Maturation of long-term potentiation in the hippocampal dentate gyrus of the freely moving rat. AB - The ability of the perforant path/dentate granule cell synapse of the hippocampal formation to establish and maintain enhanced levels of synaptic transmission in response to tetanization (long-term potentiation, LTP) was investigated in freely moving rats at 15, 30, and 90 days of age. Measures of 1) the slope of the population excitatory postsynaptic potential (EPSP), and 2) the population spike amplitude (PSA) obtained before, and at several times following tetanization, were used to evaluate the magnitude and duration of LTP as a function of age. Significant enhancement of both EPSP slope and PSA measures was obtained from animals of all three ages in response to perforant path tetanization. The initial degree of enhancement was essentially the same across the age groups, ranging from +27% to +38% of pretetanization levels for EPSP slope measures and +60% to +75% of pretetanization levels for PSA measures, obtained 15 min after tetanization. The duration of this enhancement obtained from animals of the preweaning group was significantly longer than that obtained from either 30- or 90-day-old animals. Enhanced measures of both EPSP slope and PSA decayed to baseline levels in these older animals 18 to 24 h after tetanization, while animals tetanized at 15 days of age maintained potentiated levels of both measures for a period of 5 days following tetanization. Tetanization of 15-day old animals resulted in a significant reduction in the latency to EPSP onset without affecting the time-based relationships among the other measured parameters, which included latency of the population spike onset, population spike minimum, and population spike offset.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874236 TI - Potassium-induced long-term potentiation in area CA1 of the hippocampus involves phospholipase activation. AB - Previous studies have shown that potassium-induced long-term potentiation (LTP) of the Schaffer collateral/commissural synapses in area CA1 of the hippocampus shares common properties with tetanus-induced LTP. In the present investigation, we performed electrophysiological and binding experiments on CA1 hippocampal slices to evaluate the location and nature of the changes underlying potassium induced LTP. Paired-pulse facilitation, which represents an index of transmitter release, was markedly reduced by potassium-induced LTP. In addition, KCl-induced LTP was associated with an increase in 3H-AMPA ([3H]-amino-3-hydroxy-5 methylisoxazole-4-propionate) binding to CA1 synaptic membranes when measured 40 min after high-potassium exposure; however, no changes were detected in binding of an antagonist ([3H]-6-cyano-7-nitroquinoxaline-2,3-dione; 3H-CNQX) to AMPA receptors in slices expressing KCl-induced LTP. Administration of the phospholipase A2 (PLA2) inhibitor bromophenacyl bromide (BPB) prior to potassium application prevented LTP formation as well as the changes in paired-pulse facilitation and 3H-AMPA binding that characterized this type of potentiation. Taken together, these data indicate that potassium-induced LTP may be related to modifications in both pre- and postsynaptic properties and confirm the hypothesis that PLA2 activation is an important mechanism in long-term changes of synaptic operation. PMID- 7874237 TI - The midline posterior hypothalamic region comprises a critical part of the ascending brainstem hippocampal synchronizing pathway. AB - Electrical stimulation and microinfusion techniques were utilized in acute experiments on urethane-anesthetized rats in order to evaluate the hypothesis that the posterior hypothalamic and supramammillary nuclei comprise a critical part of the ascending brainstem pathway for producing synchronous hippocampal formation (HPC) field activity (theta). Given confirmation of this hypothesis a second objective was to determine the nature of the contribution made by this midline posterior hypothalamic region (PH) to the frequency and amplitude components of HPC theta field activity. The cholinergic nature of the ascending pathway was also examined. Reversible inactivation of the PH was achieved by microinfusion of the local anesthetic procaine hydrochloride. The efficacy of and recovery from procaine inactivation of the PH was quantitatively analyzed either by electrical stimulation of the nucleus pontis oralis (PO) (two experiments) or the PH (four experiments). The results are summarized under the following three headings: 1) The first is the effect of procaine inactivation of the PH on HPC theta elicited caudal to, at the level of, or rostral to the PH. All HPC theta induced caudal to the PH (spontaneous theta, tail pinch-induced theta, and theta produced by electrical stimulation of the PO) was totally abolished for a minimum 10-min period. HPC theta induced rostral to the PH by the intrahippocampal infusion of carbachol was unaffected, while HPC theta induced by infusions of carbachol into either the medial septum (MS) or PH was reduced in amplitude with no effect on frequency. 2) Next are comparisons of pre- and post-PH procaine trials of electrical stimulation of the PO and PH. In all experiments, regardless of the anatomical locus or technique used to induce HPC theta, pre- and post-PH procaine comparisons of the PO and PH stimulation trials revealed that frequency modulation of HPC theta recovered significantly more slowly than amplitude. 3) Last is the effect of electrical stimulation of the PO and PH on HPC theta induced by carbachol infusions at the level of the HPC, MS, or PH. In all experiments, electrical stimulation of both the PO and PH, at appropriate intensities, resulted in increasing HPC theta frequencies above the frequency induced by the infusion of carbachol into the HPC, MS, and PH. In addition, the post-carbachol HPC theta frequencies induced by electrical stimulation were significantly higher than those produced in the pre-carbachol conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7874238 TI - Differential NPY mRNA expression in granule cells and interneurons of the rat dentate gyrus after kainic acid injection. AB - Using in situ hybridization histochemistry neuropeptide Y (NPY) mRNA expression was investigated after intraperitoneal injection of kainic acid (KA) and after local application of KA or quinolinic acid into the dentate gyrus of the rat. Enhanced concentrations of NPY mRNA were observed in interneurons of the hilus, including presumptive fusiform neurons and pyramidal-shaped basket cells already 4 hours after initiation of limbic seizures by KA (10 mg/kg, i.p.). Increased NPY expression persisted in neurons resistant to seizure-induced cell death (6-48 h after i.p. KA). Exceptionally high hybridization signals were found in interneurons of the hilus and the CA1 and CA3 sectors 8 months after KA-induced limbic seizures. In the granule cell layer only a transient but pronounced increase in NPY mRNA was observed 12-24 h after injection. Only moderate changes were observed in this cell layer at later intervals. Anticonvulsant treatment with thiopental, after a brief period of generalized seizures, prevented the increase in NPY mRNA in granule cells but not in interneurons. No change in NPY message was found also in granule cells of rats which responded with mild "wet dog shake" behavior but not with motor seizures to KA injection. Local injections of low doses of KA (0.05-0.2 nmol) or quinolinic acid (6.5-100 nmol) into the dentate gyrus of the hippocampus under deep thiopental anesthesia, after 24 h, resulted in increased concentrations of NPY message in interneurons of the ipsilateral, but not of the contralateral hilus and not in granule cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874239 TI - Severity of memory impairment in monkeys as a function of locus and extent of damage within the medial temporal lobe memory system. AB - During the past decade, work with monkeys has helped identify the structures in the medial temporal lobe that are important for memory: the hippocampal region (including the hippocampus proper, the dentate gyrus, and the subicular complex) and adjacent cortical areas that are anatomically linked to the hippocampus, i.e., the entorhinal, perirhinal, and parahippocampal cortices. One idea that has emerged from this work is that the severity of memory impairment might increase as more components of the medial temporal lobe are damaged. We have evaluated this idea directly by examining behavioral data from 30 monkeys (ten normal monkeys and 20 monkeys with bilateral lesions involving structures within the medial temporal lobe) that have completed testing on our standard memory battery during the last 10 years. The main finding was that the severity of memory impairment depended on the locus and extent of damage to the medial temporal lobe. Specifically, damage limited to the hippocampal region produced a mild memory impairment. More severe memory impairment was produced when the damage was increased to include the adjacent entorhinal and parahippocampal cortices (the H+ lesion). Finally, memory impairment was even more severe when the H+ lesion was extended forward to include the anterior entorhinal cortex and the perirhinal cortex (H++ lesion). Taken together, these findings suggest that, whereas damage to the hippocampal region produces measurable memory impairment, a substantial part of the severe memory impairment produced by large medial temporal lobe lesions in humans and monkeys can be attributed to damage to entorhinal, perirhinal, and parahippocampal cortices adjacent to the hippocampal region. PMID- 7874241 TI - Our patients, ourselves: will the therapeutic relationship survive health care reform? PMID- 7874240 TI - X-rays and imaging studies--a baseline review for the therapist. PMID- 7874242 TI - Early controlled motion with dynamic splinting versus static splinting for zones III and IV extensor tendon lacerations: a preliminary report. AB - Recent developments in the understanding of tendon healing and the effects of early motion have led to early controlled motion programs (ECM) for lacerated extensor tendons. The purpose of this study was to determine whether there were differences in length of treatment and final results when patients who had been treated with ECM with dynamic splinting were compared with patients who had been treated with traditional static extension splinting (SES) for zone III and zone IV extensor tendon lacerations. A retrospective study of patient charts from June 1984 through January 1990 was conducted. A total of 36 charts were reviewed. Twenty-seven patients met the study criteria: treatment with ECM with dynamic splinting (n = 10) and treatment with traditional SES using a finger-hand splint (n = 17). Data were analyzed for total number of therapy visits (V), total number of weeks of therapy before discharge (W), total active motion achieved (TAM), total passive motion achieved (TPM), and incidence of complications. Significance was established at the p = 0.05 level for all statistical analyses. There were no significant differences between the groups for V (t = 1.76, p = 0.09), W (t = 0.58, p = 0.57), TPM (t = 0.12, p = 0.90), TAM (t = 0.44, p = 0.66), or the incidence of extensor lag (chi 2 = 2.264). The Cohen stat power analysis value was 0.40, revealing that the number of patients was too small for significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874243 TI - Commercial wrist extensor orthoses. Hand function, comfort, and interference across five styles. AB - Commercial static wrist extensor orthoses are frequently used when joint support, rather than immobilization, is desired. This study compared hand function, comfort, and interference during daily tasks when 23 able-bodied women used their unencumbered dominant hands and when they wore each of five commercial static wrist extensor orthoses: Kendall-Futuro #33, AliMed Freedom Long, AliMed Freedom Short, Rolyan D-Ring, and LMB Wrist Rest. There was no significant difference in hand speeds among the orthoses for six of the seven tasks within the Jebsen Taylor Hand Function Test. However, when subject comfort and interference during daily activities were considered in conjunction with speed, the shorter padded orthosis (represented by the Rolyan D-ring) appeared to be a desirable "first choice" among the commercial orthoses that were studied. PMID- 7874244 TI - A review of the autonomic nervous system and exploration of diagnoses associated with reflex sympathetic dystrophy. AB - The hand therapy literature about reflex sympathetic dystrophy (RSD) tends to discuss this phenomenon in terms of traumatic hand or upper-extremity injury etiology. Hand therapists' bibliographies run the risk of being inbred and delimited to orthopedic and neurologic sources. Nonetheless, this well-developed body of knowledge identifies cardinal signs and symptoms, stages, and clinical types of RSD. Therapy guidelines have been well detailed in accordance with pathophysiologic explanations. The purpose of this article is to provide an overview of the autonomic nervous system (ANS), to briefly consider the history of the term "sympathetic," and to explore familiar and less well-known predisposing events and associated diagnoses. Appreciating the gamut of diagnoses associated with RSD may promote additional opportunities for hand therapist collaboration in the care for this complicated and challenging diagnostic group. PMID- 7874245 TI - Test-retest reliability of a procedure for measuring extensibility of the extrinsic finger flexor muscles. AB - This study assessed the test-retest reliability of a procedure designed to provide torque-controlled measurements of the extensibility of extrinsic finger flexor muscles. The extensibility of the extrinsic finger flexor muscles of both hands of nine patients who had spinal cord injuries was measured on two consecutive days. On each day a total of three measurements were obtained for each hand. Intraclass correlation coefficients (ICCs) and percent close agreement scores were used to assess agreement between the mean measurements obtained on day 1 and those obtained on day 2. An ICC of 0.85 was obtained. Measurements obtained on day 1 were within 5 degrees of the measurements obtained on day 2 83% of the time. The procedure is therefore sufficiently reliable for many clinical and research applications. PMID- 7874246 TI - Can co-authors remain friends? PMID- 7874247 TI - Buddy sleeves. PMID- 7874248 TI - Treatment for the mallet finger injuries of surgeons. PMID- 7874249 TI - Apoptosis in rheumatic disease. PMID- 7874250 TI - Fatigue in rheumatic disease. PMID- 7874251 TI - Fabrication of a fixed partial denture in the Class II partial edentulous mandible using the UCLA abutment: a clinical report. AB - Several methods are currently available to restore the partially edentulous patient with osseointegrated implants. The UCLA abutment eliminates the unesthetic, traditional transmucosal abutment and can provide esthetic crowns, fixed prostheses, and subgingival porcelain margins without the need for excessive instrumentation and components. A clinical report for the fabrication of a direct, implant-borne fixed prosthesis using the UCLA abutment is presented. PMID- 7874252 TI - Bond strength of adhesive composites to dental substrates. AB - PURPOSE: The purpose of this study was to evaluate the in vitro bond strength of adhesive and traditional composites to several materials that might be encountered in clinical practice. MATERIALS AND METHODS: An adhesive composite, an adhesive composite with a bonding agent, and a traditional composite with a bonding agent were bonded to enamel, dentin, amalgam, porcelain, and nickel chromium-beryllium (Ni-Cr-Be) alloy. Tensile bond strengths were determined after 24 hours storage at 23 degrees C or thermocycling. RESULTS: The use of an adhesive composite with a bonding agent resulted in increased bond strength to amalgam, porcelain, and dentin, but not to enamel or Ni-Cr-Be alloy at 23 degrees C, when compared with the adhesive composite alone. The adhesive composite with a bonding agent had higher bond strengths to amalgam, porcelain, and dentin than did the traditional composite with bonding agent, but not to enamel or Ni-Cr-Be alloy at 23 degrees C. CONCLUSIONS: The use of a bonding agent with an adhesive composite produced higher bond strengths than the adhesive composite alone. The traditional composite bonded better to enamel and Ni-Cr-Be alloy than did the adhesive composite. Thermocycling generally had no effect on bond strengths or increased them slightly. PMID- 7874253 TI - Surface cracking identified in polished and self-glazed dental porcelain. AB - PURPOSE: Polishing and glazing porcelain surfaces of restorations is thought to help reduce the wear on the opposing occlusion because of reduced roughness. MATERIALS AND METHODS: To test this theory, samples of a variety of dental porcelains were prepared and subjected to various polishing and self-glazing treatments commonly used in dentistry and then viewed using scanning electron microscope (SEM). Fine cracks were discovered in the surface of the samples that had been polished and then self-glazed. These cracks were typically greater than 50 microns in length with submicron surface openings and crack depths less than 20 microns. To establish the treatments responsible for the formation of these cracks, a more controlled study was performed. Samples of Vita VMK 68 no. 559 incisal porcelain (Vita Zahnfabrik, Bad Sachingen, Germany) were prepared and subjected to six treatments (sample size = 3): treatment no. 1, as-fired condition; treatment no. 2, self-glazed (32 degrees C per minute to 960 degrees C, then cooled); treatments no. 3 and 4, wet ground followed by 1 micron diamond polish (no. 4 was then self-glazed); treatments no. 5 and 6, ground and polished using a Shofu porcelain adjustment kit (Shofu Inc, Kyoto, Japan) (no. 6 was then self-glazed). The samples were observed using SEM. RESULTS: Treatments no. 1, 2, 3, and 5 showed no cracking; however, treatments no. 4 and 6 showed cracking in all specimens (approximate levels 5,100 microns/mm2 and 3,600 microns/mm2, respectively). CONCLUSIONS: Polishing followed by self-glazing produces fine surface cracks. The rougher surface resulting from the surface cracks and subsequent porcelain chipping may cause wear of opposing occlusal surfaces. PMID- 7874254 TI - An investigation of the rheological properties of several interocclusal registration materials. AB - PURPOSE: To study the viscosities of eight interocclusal registration materials at 30 seconds after the start of mixing and to compare the time (Tcv) required for various interocclusal registration materials to reach a proposed critical viscosity of 5,000 poise. MATERIALS AND METHODS. One zinc-oxide eugenol, one polyether, and six vinyl-polysiloxane interocclusal registration materials were studied. The viscosities of the polymerizing materials were monitored with a cone and plate viscometer. RESULTS: One-way analysis of variance showed significant difference in the viscosity at 30 seconds and in the Tcv among the materials. A zinc oxide eugenol interocclusal registration material was found to possess the lowest viscosity at 30 seconds and the longest Tcv. CONCLUSIONS: The criteria for the selection of an interocclusal registration material should include its viscous properties because all materials behaved differently. PMID- 7874255 TI - In vitro fracture behavior of ceramic and metal-ceramic restorations. AB - PURPOSE: Failed crowns and failure load data were studied to gain insights into the fracture behavior of prostheses under incisal-directed, load-to-failure testing. MATERIALS AND METHODS: Incisor crowns (n = 68) were fabricated: two all ceramic groups (feldspathic veneer on high-strength core), differing in core design, and two metal-ceramic groups, differing in metal oxidation time (30 seconds v 3 minutes). Crowns were loaded to failure on their incisal edge. Gross visual, microscopic, and elemental microprobe analyses of failed crowns were coupled with Weibull analysis of the failure load data. RESULTS: Failure loads were higher for the normal oxidation time (TN) than for the extended oxidation time (TE) metal-ceramic crowns (P < .02), but both groups had indistinguishable Weibull moduli indicating the possibility of a common failure origin. Fracture behavior and Weibull results both implicated the oxide layer as being the origin of failure. The ratio of fracture loads (TE/TN) corresponded well with calculated oxide-volume ratios. Failure loads were lower for the all-ceramic than for the metal-ceramic crowns (P < .001). Fifty percent of the all-ceramic crowns failed by delamination of veneering glass alone, leaving a thin layer of residual glass on the core surface. Scanning electron microscope views showed that delamination occurred 10 to 50 microns away from the core-veneer interface. Electron microprobe elemental analysis of the core-veneer interface showed that residual core infiltration glass was not present on the core surface and that chemical alterations in the veneering glass were apparently limited to less than a 2- to 3 microns thick layer. CONCLUSIONS: Failure for both restorative systems involved interfacial stresses with crack propagation occurring at or near the core-veneer interface. The weaker interface in the metal-ceramic system probably resulted from an increase in surface oxide volume, irrespective of any change in its adherence or physical properties. For the ceramic crowns, delamination crack fronts appeared to propagate through chemically unaltered veneering porcelain. Both the Weibull moduli and characteristic strengths were indistinguishable between either of the two ceramic core designs or between groups failing from delamination with or without core cracking/failure. This is consistent with delamination being the primary fracture process during failure. Clinical implications should not be drawn from results of this study because no correlation is known to have ever been established between clinical behavior and incisal load-to-failure results. PMID- 7874256 TI - A comparison of impression techniques for the CeraOne abutment. AB - PURPOSE: This study measured the accuracy of two impression techniques recommended by Noblepharma to be used with their CeraOne single tooth implant restoration. The first technique was to lute the impression transfer coping to the impression tray with autopolymerizing acrylic resin. The second was to leave the transfer coping free-standing in the impression material. MATERIALS AND METHODS: Thirty-five samples were made of a polyvinyl impression of the CeraOne transfer coping free-standing in the set impression material. Thirty-five samples were made of a polyvinyl impression of the CeraOne transfer coping luted to the impression tray with autopolymerizing acrylic resin. A jig was fabricated and used to record the spatial relations of the impressions and the transfer copings in reference to the jig. A light microscope was used to measure the distance between fixed markings on pressure sensitive paper, representing impression variations. RESULTS: The mean discrepancy in the horizontal plane for nonluted impressions was 0.094 mm, and for luted impressions, it was 0.275 mm. The mean discrepancy in the vertical plane for nonluted impressions was 0.154 mm, and for luted impressions, it was 0.192 mm. The differences found between the group with the luted impression tray and the group with the nonluted impression tray were found to be statistically significant. CONCLUSIONS: The more accurate of the two techniques is to transfer the impression coping without luting it to the impression tray. PMID- 7874257 TI - Effect of restoration composition, shade, and thickness on the cure of a photoactivated resin cement. AB - PURPOSE: This study investigates the effect of selected properties of a restorative material (type, shade, and thickness) on the cure of a photoactivated resin cement. MATERIALS AND METHODS: Disks of ceramic and resin-based restorative materials of two extreme shades were made to provide thicknesses of 0.5 to 3.0 mm in 0.5-mm intervals. Light transmission was measured through various thicknesses and shades of each restorative material type. The effect of light transmission, as influenced by restorative material type, shade, and thickness on resin cement cure was also determined. RESULTS: Thickness and shade of restorative material had the greatest influence on light transmission. For simulated restoration thicknesses 1.5 mm and greater, Dicor (Dentsply International Inc, York, PA) had greater transmission of light than the other materials, regardless of shade. At equal restorative material thickness, light transmission was similar for identical shades of the other three materials. Restoration shade and thickness also had the greatest influence on resin cement cure. Material type, although significant, had only a minor influence. At thicknesses of 1 to 2 mm, Dicor consistently yielded greater resin cement cure values than any other material tested. CONCLUSIONS: When considering the ability of restorative materials to transmit light for curing of photo-activated resin cements, the thickness of the restoration and its shade are much more influential than the choice of restorative material. Dicor provides greater light transmission that results in the ability to photobond restorations of greater thicknesses than the other materials. For restorations greater than 1 mm in thickness, a dual cure or chemical cure resin cement should be used to provide maximal cement properties. PMID- 7874258 TI - Evolution of removable partial denture design. AB - This is a brief overview of the progress of design philosophies of removable partial dentures. It begins in 1711 with the first published description of a removable partial denture prosthesis and continues, with discussion of the most significant discoveries, through 1990. PMID- 7874259 TI - A survey of private prosthodontic practice. AB - This article reports the data of a survey of private prosthodontic practitioners. It reports incomes, overhead expenses, staff size, and character of prosthodontic practices. The study also develops a profile for a median prosthodontic practice and practitioner. PMID- 7874260 TI - Postsurgical timing of restorative therapy: a review. AB - Knowledge of wound healing is necessary for the clinician when determining the time of prosthodontic treatment after periodontal surgery. Wound healing and longitudinal clinical studies indicate that the clinician should wait approximately 8 weeks before proceeding with the final restoration. Restorative procedures could be considered as early as 6 weeks if (1) the patient shows good systemic health; (2) injury is not inflicted on the gingiva by the restorative technique; (3) restorative margins are supragingival; and (4) esthetics are not critical. With a thick periodontium, more common in posterior areas, the gingiva often will move coronally as the tissue matures. Thin periodontal tissues may recede postsurgically, and in areas of esthetic concern, postponement of final restoration for up to 5 to 6 months may be desirable to assure gingival margin stability. Modifiers that may affect time and quality of healing, such as the patient's smoking frequency and age, should be considered when scheduling restorative treatment after periodontal surgery. PMID- 7874261 TI - The use of light-cured composite resin on altered diagnostic casts. AB - Light-cured composite resin as an alternative to wax for altered diagnostic casts is demonstrated. The value of altered diagnostic casts as a diagnostic tool is addressed. The benefits in the use of composite resin versus the traditional use of wax are emphasized. PMID- 7874262 TI - Immunohistochemical study of dopamine in rat gastric mucosa with acute gastric ulcer. AB - Recent studies have shown the presence of dopamine (DA) in gastric and duodenal mucosa, and changes in gastric mucosal DA content have been observed in patient with acute ulcers. Immunohistochemical demonstration of the distribution of DA in gastric mucosa under stress was studied by light and electron microscopy. In the control group, DA was present in the gastric gland proper in the gastric corpus and antrum on light microscopy, and on the surface of mucous granules in chief cells, mucous neck cells, and surface epithelium on electron microscopy. In the stress group, DA in gastric mucosa was almost undetectable on light and electron microscopy. Further, in this group serum DA concentration was significantly higher in the portal vein than in the abdominal aorta. Endogenous DA in gastric mucosal cells may affect gastric mucosa differently from exogenous DA, and stress may release endogenous intracellular DA into extracellular spaces. PMID- 7874263 TI - Effects of 16, 16-dimethyl prostaglandin E2 on lysosomal membrane stability in rat stomach. AB - The lysosomal membrane encloses numerous hydrolytic enzymes and prevents the cytoplasm from being damaged by these enzymes. It is possible that the fragility of this membrane may be implicated in the pathogenesis of gastric mucosal damage. We investigated the effects of 16,16-dimethyl prostaglandin E2 (dmPGE2), which is known to protect the gastric mucosa from various noxious agents, on lysosomal membrane stability in the rat stomach. Sodium taurocholate (TC) was used as the damaging agent. To assess lysosomal membrane stability in the gastric mucosa, we assayed acid phosphatase released from lysosomes isolated from a gastric mucosal homogenate. To assess lysosomal membrane stability in gastric surface epithelial cells, we used laser scanning confocal microscopy to observe the fading of red fluorescence in living cells vitally stained with acridine orange. Exogenous dmPGE2 enhanced lysosomal membrane stability in the gastric mucosa, whereas TC decreased it. In gastric surface epithelial cells, exogenous dmPGE2 protected the cells against TC-induced damage and prevented TC-induced decreased lysosomal membrane stability. It was concluded that a decrease in lysosomal membrane stability seemed to be closely involved in the pathogenesis of gastric mucosal damage. Moreover, it appears that stabilization of the lysosomal membrane by exogenous dmPGE2 may contribute to its protective effect in the gastric mucosa, both at the level of gastric surface epithelial cells and in regard to the entire gastric mucosa. PMID- 7874264 TI - Detection of minute intestinal metaplastic lesions by video microscopy. AB - Using video microscopy in 225 resected stomachs we detected 32 minute solitary lesions of intestinal metaplasia histologically. The magnified features of the minute lesions showed a characteristic appearance and were classified into three types: mesh-like (type A), villoid (type B), and tubular (type C). All the lesions classified as type A exhibited the incomplete type of intestinal metaplasia according to the results of histopathological and/or histochemical examination. In contrast, most lesions classified as type B exhibited the complete type of intestinal metaplasia. We concluded that intentional detection of minute lesions in resected stomachs by video microscopy is simple and useful, especially in cases of minute lesions < 5 mm in diameter. Moreover, our findings demonstrate that the minute intestinal metaplastic lesions have morphological characteristics based on which they can be classified into three types of lesions. These morphological characteristics correlate with their histopathological findings. PMID- 7874265 TI - Milk is a useful test meal for measurement of small bowel transit time. AB - To improve and standardize the measurement of small bowel transit time, milk was employed for the test meal instead of the conventional lactulose meal. Although 92% of the subjects were lactase deficient, only 2% were milk intolerant and 13% were lactose intolerant. Small bowel transit time with milk (milk breath hydrogen test) was 113 +/- 9 min (mean +/- SE, n = 20); the normal range calculated from the mean +/- 2 SD was 31-195 min. The coefficient of variation in the milk hydrogen breath test was 13 +/- 4% (n = 6), whereas in the lactulose hydrogen breath test, it was 39 +/- 16% (n = 10). The frequency of non-hydrogen producers, the occurrence of discomfort, and the reproducibility were better, though not significantly so, in the milk hydrogen breath test than in the lactulose. Since lactase activity in the intestine is variable in lactase-deficient subjects, small bowel transit times for milk may change from subject to subject. However, individual reproducibility of the milk hydrogen breath test is good. It could be useful for pharmacological experiments using paired comparison, for screening tests, or for the follow up of diseases in which small bowel transit time is affected. PMID- 7874266 TI - Regulation of 60-kDa heat shock protein expression by systemic stress and 5 hydroxytryptamine in rat colonic mucosa. AB - Bowel dysfunction such as irritable bowel syndrome caused by stress is well described. Previous reports suggest that 5-hydroxytryptamine (5-HT) mediates alteration of bowel motility. In this study, the effects of water-immersion stress and the administration of 5-HT on the expression of a 60-kDa heat shock protein (HSP60) in rat colonic mucosa were investigated. The effect of YM-060, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, on the expression of this protein was also studied. Water-immersion stress and the administration of 5-HT induced synthesis of HSP60 in rat colonic mucosa. The induction of HSP60 and the number of defecations were clearly inhibited by the oral administration of YM 060. Our results suggest that the induction of HSP60 in rat colonic mucosa by water-immersion stress may be associated with gastrointestinal motility mediated by 5-HT, especially via 5-HT3 receptors. PMID- 7874267 TI - Expression of cytoskeletal-associated protein tyrosine phosphatase PTPH1 mRNA in human hepatocellular carcinoma. AB - We investigated the mRNA expression of cytosolic protein tyrosine phosphatase (PTPH1), which has a homologous domain to cytoskeletal-associated proteins, in human hepatocellular carcinomas (HCCs) by using reverse transcriptase-polymerase chain reaction (RT-PCR). PTPH1 mRNA was detected in all HCC cell lines (n = 6), and HCC and adjacent noncancerous tissues (n = 8) examined, indicating that PTPH1 was expressed in HCCs and hepatocytes. There was no remarkable difference in the level expression of PTPH1 mRNA between HCC and adjacent noncancerous tissues. We also performed RT-PCR single-strand conformation polymorphism (SSCP) analysis in HCC cell lines and tissues in the C-terminal region of the catalytic domain of PTPH1. In the cHc4 cell line and a HCC tissue specimen, a shifted band was detected, although it was not found in the non-cancerous tissue of the HCC specimen. Nucleotide sequence analysis showed a common mutation from T to C at the third letter of codon 919 which did not lead to amino acid substitution. These results suggest that another mutation leading to the development of HCC could occur in some region of PTPH1 other than that investigated in this study. PMID- 7874269 TI - Anti-idiotypic antibody production in hepatitis B vaccine recipients. AB - Antibodies against hepatitis B surface antigen and against anti-hepatitis B surface antigen idiotype were assayed after immunization with hepatitis B vaccine both in sera, by enzyme-linked immunosorbent assay (ELISA), and in peripheral blood mononuclear cells, by enzyme-linked immunospot (ELISPOT) assay. After vaccination of 19 subjects, antibody to the idiotype of anti-hepatitis B surface antigen was detected in none of the sera tested with ELISA, but anti-idiotypic antibody-secreting cells were detected by ELISPOT assay in 4 (36.4%) of the 11 vaccine recipients who were positive for anti-hepatitis B surface antigen with ELISPOT assay. On the other hand, these cells were detected in none of those who remained seronegative for anti-hepatitis B surface antigen, or in the 7 normal subjects or the 2 chronic hepatitis type C patients. These results suggest that anti-idiotypic antibody production is more sensitively detected by ELISPOT assay than by ELISA, and anti-idiotypic antibodies to anti-hepatitis B surface antigen may be present in those with anti-hepatitis B surface antigen. PMID- 7874268 TI - Changes of antigen expression on human hepatoma cell lines caused by sodium butyrate, a differentiation inducer. AB - We have previously reported the effect of a differentiation inducer, sodium butyrate (SB), on human hepatocellular carcinoma (HCC) cell lines, demonstrating that it was a potent inducer of differentiation. In the present study, we investigated the alteration in expression of an antigen defined by a murine monoclonal antibody, H2, as well as alterations in the expression of other antigens, on the HCC cell lines HCC-T, HCC-M, and PLC/PRF/5, since it is known that specific antigenic changes occur during the differentiation of leukemic cells. The expression of the antigen defined by H2 increased immunocytochemically on HCC-T, HCC-M, and PLC/PRF/5 during treatment with SB. A flowcytometric study showed that almost all the HCC-T and HCC-M cells treated with SB highly expressed this antigen after 5 days' treatment. The antigen expression detected by H2 decreased after the removal of SB from the medium. On the other hand, antigen expression detected by another monoclonal antibody, 5C11, was not changed by this treatment. The expression of intracellular adhesion molecule (ICAM)-1 in HCC-T increased slightly, but that of beta 2-microglobulin and HLA-DR did not change. These results demonstrated that some antigen expression was changed by SB treatment and that the antigen defined by H2 seemed to be highly expressed on human HCC cells in the differentiated state. PMID- 7874270 TI - Elevated urokinase-type plasminogen activator plasma levels are associated with deterioration of liver function but not with hepatocellular carcinoma. AB - We measured urokinase-type plasminogen activator (u-PA) plasma levels in patients with various chronic liver diseases, including hepatocellular carcinoma (HCC), also measuring these levels in healthy volunteers. Plasma u-PA levels in the group of patients with decompensated liver cirrhosis (mean modified Pugh score of 14 points) were markedly elevated and significantly higher than those in the patients with decompensated liver cirrhosis with HCC (modified Pugh score of 10 points), those with compensated liver cirrhosis with HCC, and those with compensated liver cirrhosis. Patients in all these three latter groups had moderately and significantly elevated u-PA levels compared to levels in the chronic hepatitis group and the healthy volunteers, but the levels were not significantly different from each other. There was no relationship between u-PA plasma level and the type of HCC tumor invasion or number or size of tumors. Significant correlations were found between u-PA plasma levels and the results of seven different liver function tests in three groups without associated HCC; u-PA antigen and prothrombin time (%), hepaplastin test (%), serum cholinesterase, serum albumin, serum total cholesterol, and indocyanine green clearance correlated negatively, while u-PA antigen and serum total bilirubin correlated positively. These results suggest that plasma u-PA is associated with deterioration of liver function but not with HCC invasion. PMID- 7874271 TI - Use of immobilized histidine in assay for endotoxin in patients with liver disease. AB - The Limulus amebocyte lysate (LAL) test has the disadvantage of being influenced by various inhibitors and activators. We have developed a method for the LAL reaction that involves the specific adsorption and isolation of endotoxin using a membrane filter unit and immobilized histidine; in this present study we used the method to measure endotoxin in the plasma of patients with acute or chronic liver disease. The adsorbed endotoxins are separated from LAL-inhibitors or -activators by the membrane filter unit, and their activity is directly assayed with the LAL reagent in a filter cup without any inhibition or activation. The study population consisted of 23 subjects, 3 with fulminant hepatitis and 20 with cirrhosis (9 with esophageal varices and 11 without). All 3 (100%) of the samples of plasma from patients with fulminant hepatitis were positive for endotoxin, as were the samples of 7 (78%) of the 9 patients with cirrhosis and esophageal varices, and 2 (18%) of the 11 patients with cirrhosis but without such varices. The results suggested that this method appears to be useful for assaying the concentration of endotoxin in patients with fulminant hepatitis or cirrhosis of the liver. PMID- 7874272 TI - Dietary analysis of Japanese patients with chronic pancreatitis in stable conditions. AB - In order to examine the malnutritional condition of outpatients with pancreatitis, a dietary investigation was conducted in Japanese patients with chronic pancreatitis (n = 38) and healthy subjects (n = 35) of the same age for 3 7 consecutive days, and the characteristics of their food intake were examined. The patients with pancreatitis took in less calories, fat, carbohydrate, and protein than the healthy subjects, by 900 kcal, 20 g, 150 g, and 20 g, respectively. On the other hand, the fat energy ratio in the patients was 20%, similar to that in the healthy subjects. Also, when the fat intake was classified according to origin, i.e., animal, marine, or plant, the proportions for animal (g) and plant (g) were low, while marine fat accounted for a significantly higher percentage than in the healthy subjects. The intake of cholesterol and Ca in the patients was significantly smaller than that in the healthy subjects, but no significant difference was observed in the intake per body weight of proteins and Ca. It seems, possible that the low calorie, low protein, low fat, and low carbohydrate intake may be factors in the malnutritional condition of the patients with chronic pancreatitis. Analysis of covariance and principal component analysis showed that the body weight of the patients was closely correlated with decreases of caloric intake and intake of carbohydrate. The above results revealed that low body weight in patients with chronic pancreatitis was closely related to the decrease of calorie and carbohydrate intake, in addition to maldigestion and malabsorption of nutrients. PMID- 7874273 TI - Fibrovascular polyp of the sigmoid colon. AB - A case of a fibrovascular polyp of the sigmoid colon is reported. The patient tested positively for fecal occult blood on a mass survey for colorectal cancer, and underwent colonoscopic examination which revealed a pedunculated submucosal tumor in the sigmoid colon. The tumor, about 10 mm in diameter, had a short thin stalk and was removed endoscopically; the histological diagnosis was fibrovascular polyp. This extremely rare polyp is discussed, and particular attention is focused on the unusual endoscopic features and on the appropriate management. PMID- 7874274 TI - Radiation-induced malignant fibrous histiocytoma of the transverse colon: case report and review of the literature. AB - We report the first case, to our knowledge, of a malignant fibrous histiocytoma (MFH) of the transverse colon that seems to have been induced by radiation and we review the 12 other cases of colorectal MFH in the literature. The frequency of recurrence after radical surgery was 33% (4/12), excluding a patient with synchronous liver metastases, during the follow-up periods reported in the literature. The presence of ulceration of the tumor was a factor indicating poor prognosis (P < 0.001). Our patient had local recurrence and peritoneal metastases within only 3 months after curative resection and died 4 months after the initial operation. This case may suggest the necessity of adjuvant chemotherapy or radiotherapy in such patients, although the effectiveness of these methods has not been confirmed. PMID- 7874275 TI - Desensitization for sulfasalazine-induced skin rash in a patient with ulcerative colitis. AB - A patient with ulcerative colitis developed a sulfasalazine-induced skin allergy manifested by a urticaria rash. The patient underwent drug desensitization. The first desensitization, done according to Holdsworth's protocol, resulted in eruption with itching at a dose of 800 mg. The second desensitization, with Das's protocol, failed to reintroduce the drug because of urticarial eruptions. The third challenge, with a more gradual increase in sulfasalazine dose than that used in Holdsworth's protocol, successfully desensitized the patient. The relationship between the drug and various adverse reactions is reviewed and the desensitization to sulfasalazine is discussed. PMID- 7874276 TI - Portal vein aneurysm in the liver associated with multiple vascular malformations. AB - Portal vein aneurysm (PVA) includes focal dilatation of the portal vein, and was formerly thought to be a rare disease. We report a 46-year-old man with chronic aggressive hepatitis and intrahepatic portal vein aneurysm communicating with the hepatic vein. Hemangiomas in the liver and intracranial arteriovenous malformation (AVM) were also found. To our knowledge, this is the first report of a case of PVA in a patient with congenital intracranial AVM. As the PVA in this patient communicated with the hepatic vein, and as hemangiomas in the liver and intracranial AVM were also present, the pathogenesis in this patient seems to have been congenital anomaly of the vasculature. PMID- 7874277 TI - A case of hepatocolic fistula after percutaneous drainage for a gas-containing pyogenic liver abscess. AB - We describe a rare case of gas-containing pyogenic liver abscess which penetrated the adjacent colon, forming a hepatocolic fistula, after percutaneous transhepatic abscess drainage (PTAD) had been performed. To the best of our knowledge, this is the first report of hepatocolic fistula associated with a gas forming liver abscess in a diabetic patient, with radiological and surgical confirmation of the fistula. PMID- 7874278 TI - Pancreatic carcinoma accompanied by pseudocyst: report of two cases. AB - Two cases of pancreatic cancer accompanied by pseudocyst are reported. Case 1 was a 60-year-old man who was admitted to our hospital complaining of left lower abdominal discomfort. A cystic lesion, about 3 cm in diameter, was found in the pancreatic tail by ultrasonography (US) and computed tomography (CT). No signs of chronic pancreatitis were found. At operation, an elastic, hard, white tumor, about 1 cm in diameter, was felt adjacent to the cystic lesion on the duodenal side. Histologically, this tumor was a duct cell carcinoma with an adjacent pseudocyst upstream of the pancreas. Case 2 was a 57-year-old man who complained of back pain and loss of body weight. US and CT examination revealed a cystic lesion, 11 x 7 cm in size, in the tail of the pancreas. Histological examination of the resected specimen revealed both a duct cell carcinoma, 3 cm in size, in the body of the pancreas and a pseudocyst, 9 cm in size. Pseudocysts accompanying carcinoma are thought to develop from obstruction of the pancreatic duct by the carcinoma, followed by intraductal high pressure and disruption of ductules upstream of the pancreas. Thus, we should pay careful attention to pseudocyst of the pancreas, especially when signs of diffuse chronic inflammation cannot be found, to help identify duct cell carcinoma in the early stage. Further detailed examinations of the cyst fluid or pancreatic juice, such as cytology, tumor marker determinations, or establishment of K-ras codon 12 mutation, are needed. PMID- 7874279 TI - Endoscopic examination of the operated stomach: a review and a systematic approach. AB - The endoscopist examining a patient with a history of gastric surgery is expected to know details of the history, the present physical condition, and relevant laboratory results. Familiarity with the appropriateness or limitations of different types of fiberscopes in relation to the individual case, and knowledge of how to overcome common difficulties, is important. The preparation must address the particular characteristics of the case, and the endoscopist must be aware of contraindications, complications, and recommendations to be observed in special circumstances. Based on situations confronted in daily practice, the authors suggest a systematic approach to the examination of patients with a history of gastric surgery, and point to the importance of observing the following steps: measurement of the length of the greater curvature in the gastric stump, verification of artifacts and anatomic modifications and their repercussions, removal of symptomatic suture line or staples, dilatation of strictures, fragmentation of bezoars, exeresis of polypoid lesions, collection of tissue samples, and regular follow up of the patients. PMID- 7874280 TI - Acetylcholine regulates glucagon secretion from human glucagonoma cells. AB - Human glucagonoma cells were isolated and maintained in vitro. Incubation experiments showed that carbachol (Cch) induced the simultaneous release of glucagon, VIP (vasoactive intestinal polypeptide), and pancreatic polypeptide (PP) at levels significantly higher than basal levels. Atropine abolished the stimulatory effect of Cch on glucagon, VIP, and PP release. An immunohistological study of the tumor tissues revealed that the cells contained glucagon, VIP, and PP. These findings demonstrate, for the first time, the in vitro release of glucagon from glucagonoma cells by Cch stimulation. PMID- 7874281 TI - Biliary excretion of lipopolysaccharide is microtubule-dependent in isolated perfused rat liver. PMID- 7874282 TI - [The morphofunctional status of the epithelial spermatogenic layer of the seminiferous tubules in rats in the postresuscitation period]. AB - The state of spermatogenesis and permeability of the hemato-testicular barrier with respect to acridine orange was studied in mature male rats under conditions of the special longterm hypoxia (12-T min clinical death) and the following postreanimation period. Longterm hypoxia, as well as the complex of endogenous pathological factors of the postreanimation period leads to the degenerative changes of the maturing germ cells (nuclear vacuolization, rough chromatin condensation, cytoplasm enlightenment), their death up to the complete desolation of the certain coiled seminiferous tubules. The appearance of atypical forms of the germ cells (multinuclear elements, cells with giant nuclei) is noted, the disturbance of the synchronism of the germ cells maturation in certain coiled seminiferous tubules took place. Luminescent method revealed the change of the permeability of the hemato-testicular barrier in the certain region of coiled seminiferous tubules with respect to acridine orange. PMID- 7874283 TI - [A mathematical model of the physiological estrous cycle in outbred rats]. AB - The mathematical model of the physiological estrous cycle of the laboratory rat was developed. The data on physiological concentration of the hormones, participating in the estrous cycle regulation and admittances on the growth and selection of the ovarian follicles made the base of the model. The developed system of differentiated equations allowed to reproduce quiet precisely the duration of the estrous cycle phases, to follow up the behaviour of the apparent cohort of the growing ovarian follicles during several cycles. The model is a base for the studying of the effect of the different factors on the estrous cycle. PMID- 7874284 TI - [Is not the traditional subdivision of the human placenta into fetal and maternal portions a mistake?]. PMID- 7874285 TI - [The law of the conservation of the structural organization of living systems]. PMID- 7874286 TI - [Is the formation of intercellular contacts de novo possible?]. PMID- 7874287 TI - [The results of an experiment in studying human anatomy with the free attendance at practical lessons by students of the day department]. PMID- 7874288 TI - [The concepts of P. G. Svetlov on the critical periods of development and their significance for modern embryology (on the centenary of his birth]. PMID- 7874289 TI - [The fundamental work of P. F. Lesgaft "The bases of theoretical anatomy" (on the centenary of its publication)]. PMID- 7874290 TI - [The effect of angiogenin on blood vessel proliferation in rats]. AB - Human gene-engineering angiogenin, administered in methylcellulose tablets into the rat cornea induces growth of the limbus blood vessels in nanogram doses. Speed of the growth of the newly forming capillaries increases with the angiogenin dose. Pancreatic ribonuclease, highly homologous in structure with angiogenin does not induce neovascularization under the same conditions. Activation of the blood vessels proliferation under the effect of angiogenin was also observed in rat skin, but at higher doses. Angiogenin injected in 3% agarose with low melting point into abdominal skin or into the ear skin induced neovascularization in doses no less than 3 mg. Conditions, envisaging depression of the tissue immune reactions to the heterogeneous protein did not eliminate the angiogenin effect. This allows to conclude that they are caused by the direct manifestation of the angiogenic qualities of the studies growth factor. PMID- 7874291 TI - [The quantitative characteristics of the blood microcirculatory bed of the human prostate in postnatal ontogeny]. AB - By means of macro-microscopic and histologic methods an intraorgan vascular bed of the human prostate gland was studied in postnatal ontogenesis. Components of microcirculatory bed were demonstrated, its ontogenetic transformations were followed up, the specific volume of the vascular bed, connective tissue framework and parenchyma was estimated. PMID- 7874292 TI - [Changes in the inguinal lymph nodes of dogs subjected to individually measured physical loads]. AB - The inguinal lymph nodes (ILN) of 35 mature dogs were studied. Single individually dosed physical load causes destructive changes in ILN both on cell (widening of the perinuclear region, appearance of the great amount of vacuoles in cytoplasm, destruction of the mitochondria christal, rupture of the nuclear membrane) and tissue level (increase of the number of degeneratively changed cells, decrease of the number of the medium lymphocyte). Activity of succinate and lactate-dehydro-genases and alcaline phosphatase increases, with irregular distribution of the reaction products in the ILN section. Systematic training of the animals with such loads not only prevents unfavourable changes in ILN but also results in the increase of the proportion of blast cells, number of cells with the mitotic figures, appearance of the great amount of the lymph nodules with germinal centres. Enzyme activities in ILN of these animals were lower and had an even distribution of reaction products. PMID- 7874293 TI - [The individual typological characteristics of the habitus of young children and the principles of somatotyping]. AB - The nature of individual differences in early childhood was investigated by the principal component analysis of 22 absolute anthropological measures. The first principal component accounted for 45% of variability; it may be referred to as a general body-size factor, the same as in the studies of senior children and adults. The second principal component accounted for 14% of differences in habitus of children. Sex differences were inconsiderable. The concordance of the topology based on the values of two first principal components and on the V. G. Shtefko and A. D. Ostrovskii classifying system was lower than 50%. PMID- 7874294 TI - [The topographic anatomical validation of sphincteroplasty using a flap of the musculus adductor longus]. AB - It is stated on the base of angioarchitectonics and innervation research of the long femoral adductor muscle, that the fascicle with the muscle branches of the long femoral adductor muscle should be considered to be the major vascular nervous one. Only the transplants, cut out of the upper and middle one third of the muscle can be used for sphincteroplasty. PMID- 7874295 TI - [The effect of the fluid medium on the completeness of skin restoration in rats]. AB - Extent of the completeness of the tail skin restoration was studied in 30 outbred albino male rats after the induction of full-thickness defect 10 x 5 mm in size with the restoration process running under different conditions: without any effects (control group), with the constant perfusion, of the wounded surface with 0.9% sodium chloride solution up to the complete wound epithelialisation (experimental group 1), with the moisturing of the wounded surface by the gauze napkin, plentifully moisted with the 0.9% sodium chloride solution up to the complete epithelialisation (experimental group 2). Two months after the operation the defect control part was represented by the connective tissue scar in the control group and in the experimental group 2. Structures, resembling the terminal regions of the sebaceous glands, are developing from the newly formed epithelium in the experimental 1. The composition of the regenerate connective tissue closely resembles that of the intact derm. Thus, the constant perfusion of the wounded surface with the isotonic sodium chloride solution promotes the organotypic skin regeneration. PMID- 7874296 TI - [Human lung connective tissue in postnatal ontogeny]. AB - Changes of the connective tissue structures, appearing during all postnatal ontogenesis stages were studied in 147 human lung specimens of different age groups (from newborns up to 82-year-olds). Qualitative and quantitative composition of connective tissue structures changes with the age which leads to the lateral aggregation of the fibers and growth of the general mass of the connective tissue. Heterochronia of the age variability manifestations in different regions of the lung framework was demonstrated. The original age transformations of connective tissue structures are characteristic for the basal lung regions. With the exception of perivasal connective tissue, similar changes in the region of the lung apexes appear 3-5 years later. This gives an opportunity to distinguish three anatomic zones in the lungs in an apico-basal direction, characterising the local nature of the age changes manifestations. PMID- 7874297 TI - [The immunomorphological characteristics of collagen in the mucosa of human bronchi]. AB - By means of immunomorphological assay the character of different collagen types distribution in human bronchial mucosa has been investigated. It has been established that collagen tends to have a marked topographic specificity of distribution in human bronchial mucosa. Collagens of the I and the III types are mostly distributed in basal membranes of mucous glands' terminal parts. Collagens of the IV type are mostly intensively stained in the membranes of blood vessels and in the cell membranes of epithelial cells. In subjects with chronic inflammation staining of collagen of the I type is more marked along the bundles of fibrous structures in the loose connective tissue of mucosa and submucosa. PMID- 7874298 TI - [The structural organization of the synaptic connections of the motor neurons in the mammalian spinal cord]. AB - Peculiarities of the synaptic organization of the motor neurons of the spinal cord of the rodents (rats), predators (cats), primates (Macaca rhesus monkeys) were studied in the early stages of the postnatal ontogenesis and in the adult animals. The motor nucleus region of the lumbar thickening was studied both in normal animals and after the experimental destruction of cerebral nuclei. A new view on the structural-spatial organization of the motor neuron dendrites, the branches of which are highly specialized in the perception of the efferent inputs, is gained. By means of light and electron microscope, the types of synapses, composed of the terminations of the fibers of three major supraspinal systems of the motor control (reticulo-, vestibulo- and rubro-spinal) were studied. Lower mammals are found to have electrotonic and mixed electro-chemical synapses, along with the chemical ones. The fundamental regularities of the distribution of the synaptic inputs of different modality on the somato-dendritic membranes of the motor neurons, specifically the grouping of the chemical synapses and definitive regions of the membrane and those of electrical ones in one microzone were stated. The functional significance of the different types of synapses is discussed with the reference to modern neurology data. PMID- 7874299 TI - [The structure and cytophysiology of the endocrinocytes of the gastric epithelium in a disordered food regimen]. AB - By means of the light and electron microscopic methods the differentiation and the genesis of the epithelium endocrinocytes of the stomach mucous membrane were studied in the albino rats, fasted for 72-144 hours. The deprivation of food is followed by the increase of the number of endocrinocytes and by the change of their ultrastructure. The latter demonstrates the delay of the elimination of the secretory material in some cells (ECL, G, D, D1 cells) while the active functional condition was found in the others (ECL, A-like cells). Exo-endocrine cells with the EC or A-type granules are found in the epithelium, which is regarded as a mechanism aimed at the increase of the number of the appropriate (ECL or A-type of endocrinocytes, participating in the general metabolism of the organism. PMID- 7874300 TI - Diol-bonded silica gel as a restricted access packing forming a binary-layered phase for direct injection of serum for the determination of drugs. AB - Direct serum injection for drug determinations can be achieved on a diol-bonded silica gel as a restricted access packing. The diol-bonded phase, 3-(2,3 dihydroxypropoxy)propylsilylsilica, contains two different functions, a hydrophilic function at the tip of the single chemical bond and a hydrophobic function on the inside part of the bond to form a "binary-layered phase" on the support surface. Proteins, as large molecules, contact only the hydrophilic surface of the diol phase, and they are eluted at the solvent front based on size exclusion chromatography. On the other hand, small molecules such as synthetic drugs are retained on the internal hydrophobic function and separate based on reversed-phase chromatography. Accordingly, the diol-bonded silica gel performs as a restricted access packing for direct serum injection for the determination of relatively hydrophobic drugs. PMID- 7874301 TI - Recognition of alpha-helical peptide structures using high-performance liquid chromatographic retention data for D-amino acid analogues: influence of peptide amphipathicity and of stationary phase hydrophobicity. AB - The reversed-phase HPLC behaviour of double D-amino acid replacement sets of amphipathic and non-amphipathic helix-forming peptides consisting exclusively of leucine, lysine and alanine residues was studied on different polymer encapsulated silica-based stationary phases. Plotting the retention times versus the position of D-amino acid substitution gives a characteristic pattern showing decreased retention times in the helical region. The retention time profile obtained using an amphipathic alpha-helix is caused by disturbance of the preferred binding domain of the stationary phase-bound peptide. However, the effect is similar but less pronounced using a non-amphipathic helical peptide that is unable to interact by a preferred binding site. The results demonstrate that reversed-phase HPLC data for peptide analogues provide an indication event of a non-amphipathic helical structure in peptides. PMID- 7874302 TI - Highly enantioselective capillary electrophoretic separations with dilute solutions of the macrocyclic antibiotic ristocetin A. AB - Ristocetin A is one of a series of structurally related amphoteric, glycopeptide, macrocyclic antibiotics. These compounds have several features that make them attractive as chiral selectors. These include spatially oriented functional groups that are known to provide the types of interactions that are conducive to enantio-recognition, a somewhat rigid "pocket" that can provide a site for hydrophobic interactions and polar, flexible arms (i.e., pendent sugar moieties) that can rotate to hydrogen bond and otherwise interact with a variety of chiral analytes. In addition, these compounds are sufficiently soluble in water, aqueous buffers and aqueous-organic solvents that are commonly used in capillary electrophoresis (CE). The use and optimization of ristocetin A as a chiral selector in CE is discussed. Over 120 racemates are resolved including a variety of N-blocked amino acids, non-steroidal anti-inflammatory compounds and a large number of biologically important compounds containing carboxylic acid groups (e.g., mandelic acid derivatives, lactic acid derivatives, folinic acid, tropic acid). PMID- 7874303 TI - Reduced synchronization in the visual cortex of cats with strabismic amblyopia. AB - Synchronous firing of spatially separate neurons was studied with multi-electrode recordings in area 17 of the visual cortex of strabismic cats which had developed behaviourally verified amblyopia of the deviated eye. Responses of neurons were evoked with moving light bars or gratings of different spatial frequency. Neurons driven by the normal eye displayed stronger synchronization of their responses than neurons dominated by the amblyopic eye. These interocular differences were highly significant and particularly pronounced for grating stimuli of high spatial frequency. No interocular differences were noted with respect to the amplitudes of responses to the light bars and gratings. These results suggest reduced synchronization of population responses as a neurophysiological correlate of strabismic amblyopia and underline the importance of correlated firing of spatially separate cortical neurons for normal processing of visual information. PMID- 7874304 TI - The contribution of GABA-mediated inhibition to response properties of neurons in the nucleus of the optic tract in the rat. AB - The contribution of GABA-mediated inhibition to the generation of directional selectivity of neurons in the nucleus of the optic tract (NOT) and the dorsal terminal nucleus of the accessory optic system (DTN) was examined in anaesthetized rats by iontophoretic application of the GABAA receptor antagonist bicuculline methiodide. Spontaneous and visually evoked NOT-DTN cell activities were always increased by bicuculline application. The directional selectivity of NOT-DTN cells to slowly moving whole-field stimuli, expressed as the direction index, was reduced for most neurons. However, the difference between firing rates during stimulus movements in the preferred and in the non-preferred direction did not change systematically. On average, this difference was not significantly affected in the majority of the neurons, although bicuculline more strongly increased the activity during movement in the preferred or non-preferred direction in some of the neurons. These results indicate that directionally selective neurons in the rat NOT-DTN receive GABAergic inhibition which is most likely tonic and independent of the stimulus direction. PMID- 7874305 TI - Involvement of AMPA receptors in trigeminal post-synaptic potentials recorded in rat abducens motoneurons in vivo. AB - The pharmacology of trigeminal excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the vibrissal pad was investigated in vivo in rat abducens motoneurons using intracellular recordings combined with microionophoretic applications of excitatory amino acid agonists [alpha-amino-3 hydroxy-5-methyl-4-isoxazolepropionate (AMPA), NMDA, kainate] and a selective non NMDA receptor antagonist (GYKI-52466). Intravenous applications of GYKI-52466 were also performed during synaptic and amino acid excitations. GYKI-52466, applied intravenously or microionophoretically, reversibly antagonized AMPA induced depolarizations and trigeminal EPSPs in rat abducens motoneurons without affecting NMDA and kainate responses. The inhibition of AMPA-induced depolarizations was similar following i.v. and ionophoretic applications of GYKI 52466. Intravenous applications of GYKI-52466 (0.3-4 mg/kg) reversibly and dose dependently reduced trigeminal EPSPs, which could be totally suppressed at the highest doses of GYKI-52466 (2-4 mg/kg). The antagonist effect, which developed very quickly, could last several minutes and recovered gradually. The effect of GYKI-52466 on the EPSPs and AMPA responses were compared in the same motoneurons. The partial inhibition of trigeminal EPSPs during microionophoretic applications of GYKI-52466 was probably due to the distribution of the synapses in the dendritic arborization of abducens motoneurons. Our results show that AMPA receptors are involved in the generation of trigeminal EPSPs in rat abducens motoneurons in vivo. PMID- 7874306 TI - Neurotrophin-4/5 promotes survival and differentiation of rat striatal neurons developing in culture. AB - Cultures of dissociated striatal neurons from fetal rats were prepared, and were grown in the presence of neurotrophin-4/5 (NT-4/5) as well as the other known neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). We found that acute administration of NT-4/5 to 7-day-old cultures stimulates the hydrolysis of phosphatidylinositol, an event involved in neurotrophin signal transduction. Growth of striatal cultures in the presence of NT-4/5 resulted in increased cell survival, as indicated by elevations in cell number, protein content, and a measure of mitochondrial enzyme activity (MTT assay). NT-4/5 increased GABA uptake and staining intensity in these cultures, as indicated by GABA immunocytochemistry, indicating a trophic action on GABAergic neurons, the predominant neuron type in the striatum. To further identify responsive cell populations we analysed for calretinin, a calcium-binding protein known to colocalize with GABA in a number of neuronal cells. In cultures prepared from rats of embryonic day 15, NT-4/5 strongly increased the number of calretinin-positive cells as well as calretinin levels, as determined by Western blot analysis. When the cultures were prepared from embryonic day 18 rats, NT-4/5 very strongly increased the morphological differentiation of calretinin-positive cells, whereas the increase in cell number was less prominent. All effects produced by NT-4/5 were mimicked by BDNF with similar potency. NT-3 was less effective than NT-4/5 and BDNF, and its effects were limited to cultures prepared from embryonic day 15 rats, suggesting a role in the regulation of cell survival at early developmental stages. NGF did not affect any of the measured parameters. Our findings identify NT-4/5 as potent neurotrophic factor for striatal neurons, able to promote their survival and differentiation. PMID- 7874307 TI - Does practice in orientation discrimination lead to changes in the response properties of macaque inferior temporal neurons? AB - We trained two rhesus monkeys in a task in which they had to judge whether or not two successively presented gratings differed in orientation. In a first experiment, we trained a monkey for only a restricted set of orientations and then recorded from the temporal cortical visual area (TE) while he made discriminations at trained and untrained orientations. Although this orientation selective practice induced a marked anisotropy in his behavioural performance, this was not matched by a similar anisotropy in single-cell response properties. In a second experiment, we compared the response properties of TE cells in two monkeys before and after practice in the discrimination of small orientation differences. The training had no effect on either the responsiveness or the orientation tuning. We did, however, observe alterations in the pattern of response modulations induced by the behavioural context. However, these changes with practice, although present in both monkeys, were not consistent from animal to animal. The relevance of these findings for the functional significance of behavioural context dependencies of TE cells, as well as for the plasticity of TE responses, is discussed. PMID- 7874308 TI - Cultured neurons from mouse brain reproduce the muscarinic receptor profile of their tissue of origin. AB - These studies investigate the regional variations in the muscarinic acetylcholine receptor (mAChR) profiles in neuron populations of the CNS using primary neuron cultures derived from three areas of the mouse brain--the cerebral hemispheres, the mesencephalon and the medulla-pons--that have distinct mAChR systems. We first assessed the extent to which neurons reproduced their in vivo properties in culture by monitoring the binding capacity, the pharmacological profiles and the levels of mAChR transcripts in neuron cultures and their tissues of origin. We showed that the primary neuron cultures accumulated mAChRs with initial rates similar to those in vivo, had pharmacological profiles very close to those of their area of origin, and accumulated m1, m2, m3, m4 and m5 receptor transcripts according to patterns resembling those in the tissues. We conclude that most of the characteristics of the mAChRs in a given area are proper to the neuron population of that area, that the pattern is established early in ontogenesis, and that it is reproduced in vitro. We also show that the stimulation of phosphoinositide turnover is mediated by mAChRs with distinct pharmacological profiles in neuron cultures from the three brain areas. PMID- 7874309 TI - Muscarinic receptor profiles of mouse brain astrocytes in culture vary with their tissue of origin but differ from those of neurons. AB - The two main cell populations in brain tissues are neurons and astrocytes. Cultures of both bear muscarinic acetylcholine receptors (mAChRs). Available data indicate that astrocyte mACRs are heterogeneous, but the particular subtypes on these cells are not known, nor is there any information as to whether there is a regional variation in the mAChR profile of astrocytes. This paper describes the mAChR profiles of cultured astrocytes derived from the cerebral hemispheres, mesencephalon and medulla-pons, and is a continuation of our study on cultures of neurons from these same tissues. Pharmacological studies showed that astrocytes accumulated small amounts of mAChRs with distinct pharmacological profiles which, for a given area, differed from those of neurons in culture. Northern blot analyses showed transcripts for m1 and m3 mAChRs only. Their concentrations differed from one cell population to another. Astrocyte cultures from the mesencephalon contained m1 mRNA amounts close to those in the tissue. Thus, at least part of the mAChR profile in vitro might be a true reflection of the cell's properties in vivo. Functional studies showed that mAChRs mediate the stimulation of phosphoinositide turnover in all three astrocyte cultures, that the amplitude of this response varies greatly with the origin of the cell, and that two pharmacological subclasses, M1 and M1-2-, are involved in these responses, but to different extents. Thus the CNS contains discrete astrocyte populations which in culture differ in their mAChR profiles at the molecular, the pharmacological and the functional levels. PMID- 7874310 TI - Low doses of the glycine/NMDA receptor antagonist R-(+)-HA-966 but not D cycloserine induce paroxysmal activity in limbic brain regions of kindled rats. AB - (+)-HA-966 [R-(+)-3-amino-1-hydroxypyrrolid-2-one], a functional antagonist at the glycine modulatory site on the N-methyl-D-aspartate (NMDA) receptor/ion channel complex, was evaluated in amygdala-kindled rats, a model of epilepsy recently shown to exhibit enhanced susceptibility to the adverse effects of competitive and non-competitive NMDA receptor antagonists. Since (+)-HA-966 displays weak partial agonistic effects at the glycine site (approximately 10% efficacy of glycine), D-cycloserine, a glycine ligand with much higher intrinsic activity, was evaluated in kindled rats for comparison. Following drug administration, electrographic activity was recorded from the basolateral amygdala (i.e. the focal site) as well as the ipsilateral piriform cortex, ventral hippocampus and nucleus accumbens. In addition to the evaluation of original recordings, power spectrum analysis was used to delineate drug effects. (+)-HA-966 (20-40 mg/kg i.p.) induced marked alterations in electrographic recordings, including increases in amplitude and isolated spiking, i.e. signs of paroxysmal activity. The severity or duration of fully kindled seizures was not changed by (+)-HA-966, but the drug dramatically increased the duration of immobilization and limbic seizure activity following a kindled motor seizure. In contrast to (+)-HA-966, D-cycloserine did not induce any electrographic changes, even when administered in much higher doses than (+)-HA-966. The changes in electrographic recordings seen after administration of (+)-HA-966 in kindled rats were almost absent in non-kindled rats, indicating that kindling had increased the sensitivity to the paroxysmal effects of the glycine/NMDA receptor ligand. The data indicate that functional glycine/NMDA antagonists with low intrinsic efficacy may bear the risk of proconvulsant activity. PMID- 7874311 TI - Differential effects of serotonin and raphe grafts in the hippocampus and hypothalamus: a combined behavioural and anatomical study in the rat. AB - Combined with a partial cholinergic deficiency, serotonergic lesions induce severe spatial learning deficits. Serotonergic lesions, however, have additional effects, such as reduced body weight and disruption of thermoregulation, which may be the cause of the observed learning deficits. Restoration of the serotonergic innervation of the hippocampus by raphe grafts reduces these learning deficits. The effects of the grafts may result from a direct support of spatial learning but may also be an indirect result of preventing some of the other effects of serotonergic lesions. In the present study we used raphe grafts to examine the selectivity and specificity of the effects of serotonergic lesions in the rat, and used the behavioural effects as an indication of successful transplantation in order to examine the fine details of such grafts. Raphe grafts in the hippocampus did not prevent the effects of the lesions on body weight, thermoregulation and exploratory behaviour but did minimize the effects of the lesions on spatial learning. In contrast, raphe grafts in the hypothalamus reduced the effects of the lesions on thermoregulation but failed to support learning. The grafted fibres showed termination specificity with the interneurons, which is typical of the serotonergic innervation of the normal hippocampus. The results indicate that the serotonergic innervation of the hippocampus functions locally to support spatial learning. This role of serotonin is independent of its involvement in modulation of body weight, thermoregulation or exploratory behaviour. The results confirm that the modes of serotonergic action in the hippocampus include the selective innervation of specific interneuron subpopulations. PMID- 7874312 TI - Ultrastructural evidence for synaptic interactions between thalamocortical axons and subplate neurons. AB - Thalamic axons are known to accumulate in the subplate for a protracted period prior to invading the cortical plate and contacting their ultimate targets, the neurons of layer 4. We have examined the synaptic contacts made by visual and somatosensory thalamic axons during the transition period in which axons begin to leave the subplate and invade the cortical plate in the ferret. We first determined when geniculocortical axons leave the subplate and begin to grow into layer 4 of the visual cortex by injecting 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine (Dil) into the lateral geniculate nucleus (LGN). By birth most LGN axons are still confined to the subplate. Over the next 10 days LGN axons grow into layer 4, but many axons retain axonal branches within the subplate. To establish whether thalamic axons make synaptic contacts within the subplate, the anterograde tracer PHA-L was injected into thalamic nuclei of neonatal ferrets between postnatal day 3 and 12 to label thalamic axons at the electron microscope level. The analysis of the PHA-L injections confirmed the Dil data regarding the timing of ingrowth of thalamic axons into the cortical plate. At the electron microscope level, PHA-L-labelled axons were found to form synaptic contacts in the subplate. The thalamic axon terminals were presynaptic primarily to dendritic shafts and dendritic spines. Between postnatal days 12 and 20 labelled synapses were also observed within layer 4 of the cortex. The ultrastructural appearance of the synapses did not differ significantly in the subplate and cortical plate, with regard to type of postsynaptic profiles, length of postsynaptic density or presynaptic terminal size. These observations provide direct evidence that thalamocortical axons make synaptic contacts with subplate neurons, the only cell type within the subplate possessing mature dendrites and dendritic spines; they also suggest that functional interactions between thalamic axons and subplate neurons could play a role in the establishment of appropriate thalamocortical connections. PMID- 7874313 TI - HIV-1 envelope protein gp120 potentiates NMDA-evoked noradrenaline release by a direct action at rat hippocampal and cortical noradrenergic nerve endings. AB - Exposure of rat or human neocortical or hippocampal tissue to glutamate receptor agonists elicits as Ca(2+)-dependent, exocytotic-like release of previously accumulated [3H]noradrenaline through activation of both N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors colocalized on the noradrenergic axon terminals. Here we show that the NMDA (100 microM)-evoked release of [3H]noradrenaline from superfused thin layers of isolated rat hippocampal or cortical nerve endings was potentiated when the human immunodeficiency virus type 1 coat protein gp120 was added to the superfusion medium concomitantly with NMDA. The effect of gp120 (10 pM to 3 nM) on the 100 microM NMDA-evoked release of [3H]noradrenaline was concentration dependent; the maximal effect (approximately 140% potentiation) was reached at 100 pM of gp120. The protein was inactive on its own. The [3H]noradrenaline release evoked by NMDA (100 microM)+gp120 (100 pM) was prevented by classical NMDA receptor antagonists, as well as by 10 microM memantine. Neither the release evoked by NMDA nor that elicited by NMDA+gp120 was sensitive to the nitric oxide synthase inhibitor NG-nitro-L-arginine, suggesting no involvement of nitric oxide. The [3H]noradrenaline release elicited by 100 microM AMPA was unaffected by gp120. The protein potentiated the release evoked by 100 microM glutamate; the effect of 100 pM gp120 was quantitatively identical to that of 1 microM glycine, with no apparent additivity between gp120 and glycine. The antagonism by 1 microM 7-chloro-kynurenic acid of the NMDA-induced [3H]noradrenaline release was reversed by glycine or gp120.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874314 TI - Developmental shift from long-term depression to long-term potentiation at the mossy fibre synapses in the rat hippocampus. AB - During development, in the CA1 hippocampal region, long-term potentiation (LTP) starts appearing at postnatal (P) day 7 and reaches its maximal expression towards the end of the second postnatal week. However, LTP is often preceded by long-term depression (LTD), an activity-dependent and long-lasting reduction of synaptic strength. LTD can be induced by sustained, low-frequency stimulation of the afferent pathway and is dependent on activation of N-methyl-D-aspartate (NMDA) receptors. We report here that, in the CA3 hippocampal region, during a critical period of postnatal development, between P6 and P14, a high-frequency stimulation train (100 Hz, 1 s) to the mossy fibres in the presence of the NMDA receptor antagonist (+)-3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP; 20 microM) induced LTD. The depression of the amplitude of the field excitatory postsynaptic potential (EPSP) was 28 +/- 7% (n = 21). This form of LTD was NMDA-independent and synapse-specific. When a tetanus was applied in the presence of CPP and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM), which blocked the field EPSP, it failed to induce LTD upon washout of CNQX. LTD was probably postsynaptic in origin since it did not affect paired-pulse facilitation. A rise in extracellular calcium concentration (from 2 to 4 mM) produced LTP instead of LTD. At the end of the second postnatal week, the same high-frequency stimulation train to the mossy fibres induced LTP as in adult neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874315 TI - Fast inhibition of inwardly rectifying K+ channels by multiple neurotransmitter receptors in oligodendroglia. AB - An essential function of myelinating oligodendroglia in the mammalian central nervous system is the regulation of extracellular potassium levels by means of a prominent inwardly rectifying K+ current. Cardiac and neuronal K+ inward rectifiers are either activated by hyperpolarizing voltages or controlled by neurotransmitters through the action of receptor-activated G proteins. Neuromodulation of inward rectifiers has not previously been considered as a way to regulate oligodendrocyte function. Here we report the expression of serotonin, somatostatin and muscarinic acetylcholine G protein-coupled receptors in rat brain oligodendrocytes. Activation of these receptors leads to pertussis toxin sensitive inhibition of inwardly rectifying K+ channels within < 1 s. By contrast, in the heart and in neurons, similar pathways activate an inwardly rectifying conductance. Thus, transmitter-mediated blockade of inward rectifiers appears to be an oligodendrocyte-specific variation of a common motif for convergent signalling pathways. In vivo, expression of this mechanism, which may be dependent on neuron-glia signalling, may have a regulatory role in K+ homeostasis during neuron activity in the central nervous system. PMID- 7874316 TI - Differential expression of synaptophysin and synaptoporin during pre- and postnatal development of the rat hippocampal network. AB - The closely related synaptic vesicle membrane proteins synaptophysin and synaptoporin are abundant in the hippocampal formation of the adult rat. But the prenatal hippocampal formation contains only synaptophysin, which is first detected at embryonic day 17 (E17) in perikarya and axons of the pyramidal neurons. At E21 synaptophysin immunoreactivity extends into the apical dendrites of these cells and in newly formed terminals contacting these dendrites. The transient presence of synaptophysin in axons and dendrites suggests a functional involvement of synaptophysin in fibre outgrowth of developing pyramidal neurons. Synaptoporin expression parallels the formation of dentate granule cell synaptic contacts with pyramidal neurons: the amount of hippocampal synaptoporin, determined in immunoblots and by synaptoporin immunostaining of developing mossy fibre terminals; increases during the first postnatal week. Moreover, in the adult, synaptoporin is found exclusively in the mossy fibre terminals present in the hilar region of the dentate gyrus and the regio inferior of the cornu ammonis. In contrast, synaptophysin is present in all synaptic fields of the hippocampal formation, including the mossy fibre terminals, where it colocalizes with synaptoporin in the same boutons. Our data indicate that granule neuron terminals differ from all other terminals of the hippocampal formation by the presence of both synaptoporin and synaptophysin. This difference, observed in the earliest synaptic contacts in the postnatal hippocampus and persisting into adult life, suggests distinct functions of synaptoporin in these nerve terminals. PMID- 7874317 TI - T cells, cytokines, IgE and allergic airways inflammation. AB - Great progress in the knowledge of the cellular and molecular signals involved in IgE antibody synthesis and in the induction of allergic inflammation has been achieved. A great deal of data support the view that Th-2-like cells are the main type of cells required for IgE production and are able to orchestrate allergic tissue inflammation. In particular, a reciprocal role for IL-4 (positive)- and IFN-gamma (negative)-producing CD4+ Th cells in the regulation of human IgE synthesis has been proven. However, a physical membrane interaction between T and B cells is required for IL-4-dependent IgE synthesis. The analysis of cytokine production by allergen-specific T cells has demonstrated that the great majority of these cells, derived from the peripheral blood of atopic patients, express a Th-2/Th-0 phenotype. Furthermore, in atopic subjects, aberrant in vitro production of IL-4 and IL-5, even in response to bacterial antigens, is displayed by CD4+ T cell clones. There is a general consensus on the accumulation of Th-2 like cells at the level of the target tissues of allergic inflammation such as the respiratory mucosa during allergic rhinitis and asthma, and at the level of the skin during atopic dermatitis. Even in other forms of bronchial asthma (intrinsic and occupational asthma), particular subsets of T cells, able to produce IL-2 and IL-5 but not IL-4, may play an important role. A great effort on the characterization of the factors that may favor the development in atopics of Th cells into Th-2-like cells has been made.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874318 TI - Comparison of the immunopathology of extrinsic, intrinsic and occupational asthma. AB - Using immunohistochemistry and a panel of monoclonal antibodies we have compared T lymphocyte, eosinophil, macrophage and neutrophil infiltration and expression of adhesion receptors (ICAM-1, E-selectin and VCAM-1) in bronchial biopsies from 10 intrinsic asthmatics, 9 isocyanate-induced asthmatics, 10 extrinsic asthmatics and 12 normal healthy nonatopic controls. There was a significant increase in the number of CD25+ (interleukin-2 receptor [IL-2R]-bearing) cells (p < 0.01) in isocyanate-induced asthma compared with that of controls. There were also significant increases in MBP+ cells (p < 0.02) and EG2+ cells (p < 0.01), which represent total and activated eosinophils. CD25+ (p < 0.01), MBP+ (p < 0.03) and EG2+ (p < 0.01) cells were also elevated in extrinsic asthma. An intense mononuclear cell infiltrate was identified in intrinsic asthmatics with an increase in the number of CD45+ cells (total leukocytes), CD3+ and CD4+ T lymphocytes and CD68+ macrophages (p < 0.03, p < 0.01, p < 0.03 and p < 0.03, respectively), compared with normal controls. CD25+ cells (IL-2R+) and the number of MBP+ and actively secreting eosinophils were also increased in intrinsic asthmatics compared with normal controls (p < 0.01, p < 0.01 and p < 0.01, respectively). EG2+ cell numbers in intrinsic asthma correlated with the Aas symptom score (r = 0.65, p < 0.05), where EG2+ cell numbers in intrinsic and extrinsic asthmatics correlated with airways methacholine responsiveness (r = 0.5, p < 0.03) and the Aas symptom score (r = 0.54, p < 0.03). There was constitutive expression of ICAM-1, E-selectin and VCAM-1 in patients with asthma (intrinsic and extrinsic) and normal controls. Compared with controls, ICAM-1 and E-selectin staining in the submucosa was increased in intrinsic asthma both for intensity (p < 0.02, p < 0.05) and extent of staining (p < 0.01, p < 0.05). Epithelial expression of ICAM-1 was more frequent in asthmatics than control subjects (p < 0.05). These results suggest that T cell activation and eosinophil infiltration are features common to asthma of diverse etiology. There appears to be a complex pattern in in vivo of regulation for ICAM-1, E-selectin and VCAM-1, where they may reflect the degree of ongoing inflammation in asthma. PMID- 7874319 TI - Measurement of salivary, urinary and fecal secretory IgA levels in children with partial or total IgA deficiency. AB - We measured salivary, urinary and fecal secretory IgA (sIgA) levels in 11 children with total IgA deficiency and in 6 children with partial IgA deficiency using an ELISA technique. This was based on flexible microplates coated with antisecretory component (SC) and peroxidase-conjugated anti-IgA as a second antibody. Selective IgA deficiency is diagnosed as a serum IgA concentration < or = 0.05 g/l; partial IgA deficiency is diagnosed as a serum concentration of IgA > 0.05 g/l but 2 SD below normal levels. No salivary or fecal sIgA, and only low levels of urinary sIgA, were detected in the selective IgA-deficient group. The partial IgA-deficient children presented with low levels of salivary, urinary and fecal sIgA. Fecal sIgA levels correlated with salivary sIgA levels (p < 0.01) but not with urinary sIgA levels (p > 0.05) in the IgA-deficient patients. We found that all the children with partial IgA deficiency, except one, had detectable, but low values of secretory IgA. Our data suggest that these patients also have a partial mucosal IgA deficiency. PMID- 7874320 TI - Measurement of hookworm infection intensity and circulating levels of IgE and autoantibodies to IgE in atopics and nonatopics living in a parasitized community in Papua New Guinea. AB - We have compared hookworm infection intensity, as determined by fecal egg count, and circulating levels of IgE and autoantibodies to IgE in atopic and nonatopic parasitized (predominantly hookworm-infected) patients from Kebasob village on Karkar Island, Papua New Guinea. Our study has clearly established that parasitized atopic individuals have significantly higher levels of IgE and autoanti-IgE than their nonatopic counterparts, and that atopy does not appear to influence accumulated levels of hookworm infection. These data, therefore, do not support an earlier report that suggested that the atopic state may confer increased resistance to hookworm infestation in a parasitized community in Papua New Guinea. PMID- 7874321 TI - Serum sickness due to bovine serum albumin sensitization during in vitro fertilization. AB - Of 32 women included in the in vitro fertilization (IVF) program in our hospital in 1987, in whom a medium containing bovine serum albumin (BSA) (Menezo's medium) was employed for rinsing follicles, 5 (15%) developed a symptom complex compatible with serum sickness within 8-12 days after oocyte retrieval by echographic puncture. All the patients had specific IgG antibodies against BSA, and intradermal skin testing with BSA and Menezo's medium were positive. We could not demonstrate the presence of specific IgE against BSA in serum by RAST, probably due to the presence of high levels of specific IgG antibodies, which can interfere in the RAST procedure. Statistical analysis showed that the volume of Menezo's medium was significantly greater (p < 0.05) in patients developing the disease. The risk of disease development is directly related to the amount of heterologous protein administrated. PMID- 7874322 TI - Safety of specific immunotherapy: a retrospective study. AB - A large experience in specific immunotherapy is reviewed in order to assess the safety of this treatment. From 1968 through September 30, 1993, 300,086 injections were administered to 6,319 patients suffering from allergic asthma and/or rhinitis. Systemic reactions reported during the whole period were 184 (0.061%) in 134 subjects (2.1%) and consisted of: urticaria (59.3%), mild asthmatic attacks (23.9%), asthma and urticaria (9.7%), and spasmodic rhinitis (7.1%). The absence of cases of anaphylaxis confirms the safety of specific immunotherapy. This kind of treatment should be considered as first-line therapy, if carried out in a specialized setting. PMID- 7874323 TI - Suppression of IgA production by lymphocytes induced by diphenylhydantoin. AB - In this study, the mechanisms for suppression of immunoglobulin production by lymphocytes induced by diphenylhydantoin (DPH) were investigated using peripheral blood mononuclear cells from one patient 3 months after discontinuation of DPH, when IgA deficiency was improved. Immunoglobulin production in PBMCs was dose dependently suppressed by DPH and the suppressive effect of DPH on IgA production tended to be greater than the effect on IgM or IgG production. Moreover, cell separation experiments indicated that DPH suppresses immunoglobulin production by PBMCs through a suppression of B cell, but not T cell, function. The finding that the suppressive effect of DPH on IgA production tended to be greater than the effect on IgM or IgG production might be related to the fact that the alpha-chain gene is located in the 3' end of the gene coding the constant regions of human heavy chains. PMID- 7874324 TI - Interpretation of spirometric tests in asthmatic patients with reduced forced vital capacity. AB - We have studied 175 consecutive asthmatic patients presenting with: 1) a reversible airflow obstruction, demonstrated by an increase in the forced expiratory volume in 1 second (FEV1) or in the forced vital capacity (FVC) by at least 12% along with an absolute increase of 200 ml versus prebronchodilator values after inhalation of salbutamol; 2) FVC below the lower normal limit before administration of the bronchodilator; and 3) normal FVC or slow vital capacity after bronchodilator. Two different criteria for the lower normal limit of the FEV1/FVC ratio were used to determine whether prebronchodilator spirometric patterns could be considered obstructive or not. The use of the predicted FEV1/FVC ratio as the lower normal limit allowed correct identification of obstruction in 94.9% of the patients, whereas taking the estimated fifth percentile as the lower normal limit of the FEV1/FVC correctly identified obstruction in only 78.9% of the asthmatics. Our results suggest that the predicted FEV1/FVC ratio is an adequate estimate of the lower normal limit in asthmatic patients with reduced FVC in order to distinguish obstructive from nonobstructive patterns. PMID- 7874325 TI - The value of electrophysiologic testing in patients resuscitated from documented ventricular fibrillation. AB - INTRODUCTION: Electrophysiologic testing is performed in patients resuscitated from ventricular fibrillation (VF) on the assumption that sustained monomorphic ventricular tachycardia (VT) may be a precursor to VF, with the former amenable to assessment by serial drug testing. METHODS AND RESULTS: We assessed the usefulness of this strategy by analyzing clinical and electrophysiologic data of 42 survivors (29 men and 13 women; mean age 54 +/- 14 years) of VF without a reversible cause. All patients had VF documented on ECG and required defibrillation. Underlying heart diseases included coronary disease in 28, dilated cardiomyopathy in 3, arrhythmogenic right ventricular dysplasia in 1, and no apparent structural heart disease in 10 patients. Only 2 (4.7%) patients had a prior history of documented VT. The electrophysiologic study was performed 7 to 30 days after VF. Programmed stimulation at the right ventricular apex using at least two drive cycle lengths and up to three extrastimuli induced sustained monomorphic VT in 4 (9.5%), sustained polymorphic VT in 3 (7.1%), nonsustained monomorphic VT in 1 (2.3%), nonsustained polymorphic VT in 5 (11.9%), and VF in 13 (30.9%) patients. Two patients with documented prior VT and coronary disease had sustained VT induced during the electrophysiologic study. On the other hand, sustained monomorphic VT was induced in 53 of the 59 (90%) patients (45 men and 14 women; mean age 57 +/- 16 years) with clinically documented VT concurrently studied using the same stimulation protocol. CONCLUSION: We conclude that reproducible induction of sustained monomorphic VT in survivors of documented VF is uncommon. It may be more cost effective to proceed directly to treatment with implantable cardioverter defibrillators in these patients. PMID- 7874326 TI - Differential effect of esmolol on the fast and slow AV nodal pathways in patients with AV nodal reentrant tachycardia. AB - INTRODUCTION: AV nodal reentrant tachycardia (AVNRT) usually involves anterograde conduction over a slowly conducting ("slow") pathway and retrograde conduction over a rapidly conducting ("fast") pathway. A variety of drugs, such as beta blockers, digitalis, and calcium channel blockers, have been reported to prolong AV nodal refractoriness in both the anterograde and retrograde limbs of the circuit. However, few data are available that address whether the fast and slow pathways respond in a quantitatively different manner to drugs such as beta adrenergic antagonists. In addition, it is not known whether the effects of these agents on refractoriness parallel the effects on conduction in the fast and slow pathways. The present study was performed to measure the effect of the intravenous beta-adrenergic agent, esmolol, on refractoriness and conduction in both the fast and slow AV nodal pathways in patients with AVNRT. METHODS AND RESULTS: Thirteen patients with discontinuous AV nodal conduction properties and typical AVNRT were studied. Anterograde and retrograde AV nodal functional assessment was performed at baseline and following steady-state drug infusion of intravenous esmolol at a dose of 500 micrograms/kg for 1 minute, 150 micrograms/kg per minute for the next 4 minutes, followed by a continuous maintenance infusion of 50 to 100 micrograms/kg per minute. The anterograde effective refractory period of the fast pathway increased from 381 +/- 75 msec at baseline to 453 +/- 92 msec during the infusion of esmolol (P = 0.003). The anterograde effective refractory period of the slow pathway was also prolonged by esmolol, from 289 +/- 26 msec to 310 +/- 17 msec (P = 0.005). However, the absolute magnitude of the change in the anterograde effective refractory period of the fast pathway (+72 +/- 59 msec) was significantly greater than the change in anterograde effective refractory period of the slow pathway (+21 +/- 16 msec, P = 0.01). The mean retrograde effective refractory period of the fast pathway increased from 276 +/- 46 msec to 376 +/- 61 msec during esmolol infusion (P = 0.03). Retrograde slow pathway conduction that could not be demonstrated at baseline became manifest in three patients during esmolol infusion. In contrast to the effects of esmolol on refractoriness, the AH interval during anterograde slow pathway conduction prolonged to a far greater extent (+84 msec) than the HA interval associated with retrograde fast pathway conduction (+5 msec, P = 0.04). CONCLUSION: The beta-adrenergic antagonist, esmolol, has a quantitatively greater effect on anterograde refractoriness of the fast than the slow AV nodal pathway. However, the effects on conduction intervals during AVNRT are greater in the anterograde slow pathway than in the retrograde fast pathway. These observations suggest that the fast and slow pathways may have differential sensitivities to autonomic influences. This difference in the response to beta-adrenergic antagonists may be exploited as a clinically useful method for demonstrating slow pathway conduction in some individuals with AVNRT. PMID- 7874327 TI - Fatigue phenomenon in accessory pathways. AB - Fatigue phenomenon is transient failure of conduction following a period of repetitive excitation. Fatigue in accessory pathways is uncommon, and its electrophysiologic characteristics and clinical implications are unknown. Among the 215 patients who underwent electrophysiology studies from July 1992 to December 1993, 4 (2%) were found to exhibit fatigue over accessory pathways. The accessory pathway was posteroseptal in three patients and right free wall in one patient. The mean anterograde effective refractory period of the accessory pathway was 295 +/- 26 msec (range 270 to 330, basic drive cycle length 600 msec). Three patients had neither retrograde accessory pathway conduction nor inducible tachycardia even with infusion of isoproterenol. The fatigue phenomenon was observed after both atrial and ventricular stimulation in three patients and only after ventricular stimulation in one patient. Fatigue was dependent on duration more than rate of stimulation. We conclude that pathways exhibiting fatigue have a low margin of safety for conduction and are unlikely to be clinically problematic. PMID- 7874328 TI - Distribution of M cells in the canine ventricle. AB - INTRODUCTION: M cells and transitional cells residing in the deep structures of the ventricular free walls are distinguished by the ability of their action potentials to prolong disproportionately to those of other ventricular cells at relatively slow rates. This feature of the M cell due, at least in part, to a smaller contribution of the slowly activating component of the delayed rectifier current (IKs) is thought to contribute to the unique pharmacologic responsiveness of M cells, making them the primary targets in ventricular myocardium for agents that cause action potential prolongation and induce early and delayed afterdepolarizations and triggered activity. Previous studies dealt exclusively with the characteristics and distribution of M cells in the canine right and left ventricular free wall near the base of the ventricles. The present study uses standard microelectrode techniques to define their behavior and distribution in the apical region of the ventricular wall as well as in the endocardial structures of the ventricle, including the interventricular septum, papillary muscles, and trabeculae. METHODS AND RESULTS: Action potentials recorded from the M region (deep subepicardium) displayed similar characteristics (steep action potential duration [APD]-rate relations) in the base and apex. However, important differences were apparent in the other regions. In epicardium, the spike and dome morphology of the action potential was less accentuated and the rate dependence of APD more pronounced in the apex versus the base. In endocardium, and especially deep subendocardium, rate dependence of APD was considerably more pronounced in the apex. Transmembrane recordings from the subsurface layers of the septum, trabeculae, and papillary muscles revealed M cell behavior (steep APD rate relations) in the deep subendocardium. Epicardial and transitional behavior were also observed in the deep layers of these endocardial structures. CONCLUSION: Our results indicate that M cells reside throughout the deep subepicardial layers of the free wall of the canine left ventricle as well as in the deep subendocardial layers of the septum, papillary muscles, and trabeculae. The data also demonstrate prominent transmural as well as apicobasal gradients of phase 1 and phase 3 repolarization. These findings may have implications relative to our understanding of the electrocardiographic J wave, T wave, U wave, and long QTU intervals. PMID- 7874329 TI - Ultrastructural observations in the myocardium beyond the region of acute coagulation necrosis following radiofrequency catheter ablation. AB - INTRODUCTION: We hypothesized that myocardial injury following radiofrequency (RF) catheter ablation may extend beyond the region of acute coagulation necrosis as defined by histochemical staining. METHODS AND RESULTS: Five RF lesions were created in vivo in the left ventricle of two dogs using a 4-mm tipped ablation electrode in which RF power was adjusted to maintain an electrode-tissue interface temperature of 85 degrees C for 60 seconds. The lesions were bisected; one half of the lesions were stained with nitroblue tetrazolium (NBT) and the other half processed for electron microscopy. Three zones of interest were identified extending 0-3 mm, 3-6 mm, and > 6 mm from the visible pathologic lesion border. The degree of ultrastructural injury to the myocardium was scored for each zone. Electron microscopy demonstrated the presence of significant abnormalities of the plasma membrane, mitochondria, sarcomeres, sarcoplasmic reticulum, and gap junctions of myocytes, as well as damage to the microvasculature extending up to 6 mm beyond the pathologic lesion edge. The plasma membrane and gap junctions of myocytes and the microvasculature appeared particularly sensitive to thermal injury, whereas the intercalated discs were relatively thermally resistant. CONCLUSION: RF catheter ablation results in ultrastructural damage to the myocardium extending up to 6 mm beyond the acute pathologic RF lesion border as defined by NBT histochemical staining. PMID- 7874330 TI - Radiofrequency catheter ablation of an atriofascicular pathway during atrial fibrillation: a case report. AB - INTRODUCTION: A male patient with an atriofascicular pathway underwent catheter ablation of the atriofascicular pathway during atrial fibrillation. METHODS AND RESULTS: The patient had preexcited atrial fibrillation both clinically and repeatedly during electrophysiologic study. A preexcited tachycardia with a 1:1 AV relationship and regular RR intervals was also induced. Catheter ablation of the atriofascicular pathway could only be performed during persistent atrial fibrillation, based on mapping of the pathway's insertion into the right bundle branch. Following successful ablation and cardioversion to sinus rhythm, a regular QRS tachycardia (atrioventricular [AV] nodal reentry) having the same rate, atrial activation sequence, and His-atrial time as the regular preexcited tachycardia noted preablation was initiated. An AV nodal slow pathway modification eliminated this tachycardia. Neither atrial fibrillation nor AV nodal reentry has recurred on follow-up. CONCLUSION: This is the first report of atriofascicular mapping and ablation performed exclusively during atrial fibrillation and illustrates the utility of mapping the pathway's ventricular insertion. Other unusual features ("bystander" pathway activation during AV nodal reentry, possible role of the pathway in genesis of atrial fibrillation) are discussed. PMID- 7874331 TI - Involvement of a nodofascicular connection in supraventricular tachycardia with VA dissociation. AB - We present the case of a patient with episodes of supraventricular tachycardia and atrial dissociation that were terminated by either adenosine or verapamil. Involvement of an accessory pathway was shown by ventricular extrastimuli, elicited during His-bundle refractoriness, that interrupted the tachycardia or advanced the next His potential. The tachycardia circuit was demonstrated to be confined to the nodofascicular region based on the exclusion of surrounding tissues. Atrial activity, including that in the perinodal region, was totally dissociated during tachycardia. The lowest part of the circuit was determined to be located above the Hisian bifurcation, as multiple episodes with either a right or left bundle branch configuration during tachycardia did not modify the HH cycle. The ventricular septum summit was determined not to be involved, as no preexcitation was present during tachycardia or atrial pacing, and the right bundle branch was not part of the circuit. Radiofrequency current applied beneath the tricuspid valve at the His region successfully eliminated the nodofascicular connection with preservation of 1:1 AV conduction. The anatomical substrate underlying the abnormal connection may be either nodofasciculoventricular Mahaim fibers or a duality or dispersion of the nodo-Hisian conducting system. PMID- 7874332 TI - Basic aspects of radiofrequency catheter ablation. AB - Radiofrequency (RF) catheter ablation has become the treatment of choice for many symptomatic cardiac arrhythmias. It is presumed that the primary cause of tissue injury by RF ablation is thermally mediated, resulting in a relatively discrete homogeneous lesion. The mechanism by which RF current heats tissue is resistive heating of a narrow rim (< 1 mm) of tissue that is in direct contact with the ablation electrode. Deeper tissue heating occurs as a result of passive heat conduction from this small region of volume heating. Lesion size is proportional to the temperature at the electrode-tissue interface and the size of the ablation electrode. Temperatures above 50 degrees C are required for irreversible myocardial injury, but temperatures above 100 degrees C result in coagulum formation on the ablation electrode, a rapid rise in electrical impedance, and loss of effective tissue heating. Lesion formation is also dependent on optimal electrode-tissue contact and duration of RF delivery. Newer developments in RF ablation include temperature monitoring, longer ablation electrodes coupled to high-powered RF generators, and novel ablation electrode designs. PMID- 7874333 TI - Insights into the electrophysiology of ventricular tachycardia gained by the catheter ablation experience: "learning while burning". AB - The success of catheter ablation has significantly improved the treatment of patients with cardiac arrhythmias and has established electrophysiology as an increasingly interventional subspecialty. Some members of the electrophysiology community have expressed concern that this success has been purchased at the cost of undermining what had been our primary concern: understanding the anatomic and physiologic basis of arrhythmia syndromes. In many laboratories, endpoints such as case load and primary success have eclipsed physiologic investigation. Despite these trends, however, catheter ablation is not inherently at odds with investigation and education. On the contrary, because the lesions delivered with current techniques are much more discrete than the effects of antiarrhythmic agents or surgical ablation, catheter ablation can be used as a research tool directed toward a more precise understanding of arrhythmia substrates. Conscious attempts at "learning while burning" have already provided important and unique information about arrhythmia pathogenesis. PMID- 7874334 TI - Lev's or Lenegre's disease? PMID- 7874335 TI - Three decades of experience with emergency portacaval shunt for acutely bleeding esophageal varices in 400 unselected patients with cirrhosis of the liver. AB - BACKGROUND: Emergency treatment of acute bleeding is of singular and paramount importance in the therapy of portal hypertension and esophagogastric varices. Accordingly, for more than three decades we have conducted prospective studies of emergency therapy, and particularly of emergency portacaval shunt (EPCS). STUDY DESIGN: Emergency portacaval shunt was performed upon 400 patients with cirrhosis of the liver and acutely bleeding esophagogastric varices according to three principles: operation within eight hours of initial contact; unselected patients, meaning that no patient with variceal bleeding caused by hepatic disease was excluded from EPCS, and prospective study, meaning that a well-defined protocol was consistently used and data were collected on-line. Patients were divided into an early group of 180 treated from 1963 to 1978 and a recent group of 220 treated from 1978 to July, 1990, with similar characteristics, but strikingly different outcome. Follow-up rates at one, five, and ten years were 100, 98, and 97 percent, respectively; 96 percent of patients underwent EPCS five or more years ago. Proof of acute variceal bleeding and of cirrhosis of the liver (alcoholic in 95 percent) was obtained in every patient. Child's risk classes determined quantitatively were A in 11 percent of the patients, B in 65 percent, and C in 24 percent. All patients had a direct portacaval shunt, side-to-side in 85 percent, which reduced the mean portal vein to inferior vena cava pressure gradient from 271 to 21 mm saline solution. RESULTS: All but four patients (99 percent) had immediate and permanent control of variceal bleeding. Thrombosis of the shunt occurred in only two patients (0.5 percent). Survival rates at 30 days, five years, ten years, and 15 years in the early group were 58, 40, 30, and 30 percent, respectively, while in the recent group they were 85, 78, 71, and 57 percent, respectively (p < 0.0001). Other striking gains in the recent group were abstention from alcohol, improvement in liver function and improvement in Child's class, all in 70 percent of patients. Recurrent portal-systemic encephalopathy occurred in 9 percent of the early group and 8 percent of the recent group. CONCLUSIONS: Emergency portacaval shunt substantially improved survival and quality of life of patients with cirrhosis of the liver and bleeding varices. Our results are attributable to rapid and simplified diagnosis, prompt operation, an organized system of care, and rigorous, lifelong follow-up evaluation that emphasized abstinence from alcohol and dietary protein control. Transplantation of the liver is infrequently required in patients whose bleeding is permanently controlled. PMID- 7874336 TI - Burn center care for patients with toxic epidermal necrolysis. AB - BACKGROUND: Toxic epidermal necrolysis (TEN) is a life threatening exfoliative disorder that is most commonly precipitated by the administration of a medication. Efforts to reduce morbidity and improve survival have brought into question the use of corticosteroids and recommend the transfer of patients to a burn center to facilitate wound care. STUDY DESIGN: This study evaluated the correlation of measures of disease severity and impact of treatment strategies on morbidity and mortality in patients with TEN. The records of all patients with TEN admitted to the United States Army Institute of Surgical Research during a 12 year period were reviewed. Patient characteristics, etiologic agents, time to referral of patients to the burn center, corticosteroid therapy, and other demographic features were studied. Univariate and multivariate analyses were used to determine the significance of these factors with respect to outcome. RESULTS: The sulfonamides and phenytoin were the most frequently identified etiologic agents. Patients at the extremes of age had a higher mortality rate. The period of hospitalization was longer in patients transferred to the burn center more than seven days after skin slough. Percent of epidermalysis, white blood cell count nadir, and corticosteroid administration for more than 48 hours were independently associated with mortality. CONCLUSIONS: These data indicate that the sulfonamides and phenytoin are the most common etiologic agents, expeditious transfer to a burn center reduces morbidity, and corticosteroid administration dramatically increases mortality. PMID- 7874337 TI - Panniculectomy as an integral part of pelvic operation is an underutilized technique in patients with morbid obesity. AB - BACKGROUND: Panniculectomy integrated into pelvic procedures mandated in morbidly obese patients is a well described technique. Nevertheless, the abdominal cavity in such patients is generally approached through a vertical incision, frequently by forcibly pulling the panniculus inferiorly. Such a vertical approach has been associated with significant wound morbidity. STUDY DESIGN: Patients were offered removal of excess abdominal skin without cosmetic intent. The mean weight of patients was 126 kg and the body mass index ranged from 29.4 to 59.9. The object of this study was to discover whether or not operative access was facilitated and whether or not wound morbidity was reduced. Fifteen patients had significant medical problems and nine of the 16 had an umbilical hernia. RESULTS: Removal of the panniculus seemed to facilitate access to the abdomen, provided excellent exposure, and certainly allowed ready repair of the umbilical hernia with a Blake technique. All but one of the wounds healed by first intention, and in that patient, an 8 cm segment was easily resutured. The operative time was acceptable. There was no increased blood loss associated with the panniculectomy, but of note is the fact that the hematocrit level decreased in five patients on days 2 to 5 postoperatively without hematoma formation. CONCLUSIONS: Conservative panniculectomy to facilitate access to the pelvic area seems to be an advantageous procedure, with good wound healing, and deserves a randomized prospective study comparing it to a vertical incisional approach to validate its technical superiority. PMID- 7874338 TI - Continuous arteriovenous hemofiltration does not improve survival in a canine model of septic shock. AB - BACKGROUND: We examined whether or not continuous arteriovenous hemofiltration (CAVH), in the absence of renal failure, would improve either hemodynamic abnormalities or survival in a canine model of septic shock. STUDY DESIGN: Escherichia coli 0111, as an intraperitoneal clot, was surgically implanted into 21 one- to two-year-old purpose-bred beagles. The dogs were randomized to no CAVH (control group, n = 7), sham CAVH (extracorporeal circulation without hemofiltration, n = 7), or true CAVH (hemofiltration with removal of 600 mL/hour of ultrafiltrate, n = 7). Hemofiltration began one hour after clot implantation and continued for six hours. All dogs received antibiotics and had serial hemodynamic and laboratory evaluations. RESULTS: During the first seven hours of the study, all dogs displayed a progressive, significant decrease in mean arterial pressure, cardiac index, left ventricular ejection fraction, and serum pH (all p < 0.05). Two of seven dogs in the control group, one of seven dogs in the sham CAVH group, and one of seven dogs in the true CAVH group survived seven days after clot implantation. True CAVH, which included fluid replacement with lactated Ringer's solution, significantly increased serum lactate and decreased serum bicarbonate levels after six hours (both p < 0.05). However, pH did not differ between the three treatment groups (p > 0.20). Continuous arteriovenous hemofiltration therapy had no significant effect on cardiovascular abnormalities or survival. CONCLUSIONS: The results of this study suggest that CAVH would be unlikely to provide benefit to patients with gram-negative septic shock, in the absence of renal failure. PMID- 7874339 TI - Preoperative evaluation of the probability of common bile duct stones. French Association for Surgical Research. AB - BACKGROUND: This study was done to determine if certain criteria could predict the presence of common bile duct stones in patients with symptomatic gallstones. It was hoped that patients could be identified in whom intraoperative cholangiography was unnecessary. STUDY DESIGN: One hundred seventy-five patients, from 15 surgical centers, were prospectively enrolled. For each patient, the preoperative score (Huguier score) previously published was calculated according to clinical and ultrasound data: age, diameter of the common bile duct, diameter of the smallest gallstone, history of biliary colic, and acute cholecystitis. All patients underwent an open cholecystectomy and an intraoperative cholangiography. The absence or presence of a common bile duct stone was evaluated during the operation, if necessary, after an instrumental investigation of the common bile duct. RESULTS: Ultrasound was not interpretable in eight (5 percent) of 175 patients. Final analysis was made from the charts of the 167 remaining patients. Thirty (18 percent) had common bile duct stones. When the score was equal to or greater than 3.5, the risk of having a common bile duct stone was 24 percent (27 of 111). When the score was less than 3.5, this risk was 5 percent (three of 56). CONCLUSIONS: Huguier's score is well assessed and can be safely used. Intraoperative cholangiography could be avoided in 33 percent of patients when the score is less than 3.5 (56 of 167). PMID- 7874340 TI - Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. AB - BACKGROUND: The prognosis for patients with locally advanced carcinoma of the breast remains poor. This study examines the pathologic evidence of response of the mammary tumor and axillary nodes after preoperative chemotherapy. We sought to determine if there was a relationship between the histologic response and clinical outcome. STUDY DESIGN: Between 1987 and 1992, 36 patients with locally advanced carcinoma of the breast received three cycles of chemotherapy after incisional biopsy. Modified radical mastectomy was then performed. The breast and axillary nodes were examined pathologically for therapeutic effect and a grading scale was assigned. Postoperatively, patients received completion chemotherapy with the same agents used preoperatively followed by radiation therapy to the chest wall. RESULTS: Fourteen tumors (39 percent) showed near total therapeutic effect, five (14 percent) showed greater than 50 percent but less than total effect, 12 (33 percent) showed less than 50 percent effect, and five (14 percent) showed no effect. Nodal positivity was seen in 61 percent of the patients. Overall clinical response to induction chemotherapy was seen in 86 percent of the patients. There was poor correlation between clinical and pathologic response. Only 50 percent of the patients with complete clinical response were pathologically free of disease. Patients with excellent pathologic therapeutic response had a 79 percent overall five-year survival rate compared with 34 percent for tumors with a lesser response. This was irrespective of nodal status. While pathologic response was critical in determining outcome, clinical response was not. CONCLUSIONS: These results indicate that patients whose tumors have the best pathologic response to induction chemotherapy experience the best outcome. PMID- 7874341 TI - Complications and results of 361 hysterectomies performed at laparoscopy. AB - BACKGROUND: Before the appropriate use of laparoscopy in hysterectomy can be determined, it is necessary to evaluate the results, including complications. There must also be an accepted classification system to facilitate accurate comparison to total abdominal hysterectomy. STUDY DESIGN: We retrospectively evaluated the charts of 361 women who underwent hysterectomy for various benign pathologic conditions. Intraoperative and postoperative complication rates for hysterectomy performed at operative laparoscopy were examined. The hysterectomies were classified as one of four types according to the number of steps performed laparoscopically. All women were candidates for total abdominal hysterectomy, but not vaginal hysterectomy. RESULTS: The overall complication rate for hysterectomy performed at operative laparoscopy was 11.1 percent. Most complications were minor, including cystitis (1.66 percent), transient high fever (1.39 percent), abdominal wall ecchymosis (1.12 percent), and pneumonia and bronchitis (1.12 percent). There was no correlation between the type of laparoscopic hysterectomy performed and the complication rate. CONCLUSIONS: Our rate of intraoperative and postoperative complications associated with laparoscopic hysterectomy compares favorably with published complication rates for vaginal and abdominal hysterectomy. PMID- 7874342 TI - Endothelin-1 and prostaglandin E2 levels increase in patients with burns. AB - BACKGROUND: Endothelin-1 (ET-1), a powerful vasoconstrictor, is a 21 amino acid peptide produced by endothelium. It negatively affects pulmonary, cardiac, hepatic, and renal function. It also constricts bronchial and gut smooth muscle. This peptide also stimulates monocytes to produce prostaglandin E2 (PGE2), tumor necrosis factor, interleukin-6 and 8, and substances that stimulate neutrophil superoxide production. Plasma levels of ET-1 also increase in shock, low flow states, ischemia, and sepsis. STUDY DESIGN: Fourteen patients between the ages of seven and 72 years were admitted to the Bridgeport Hospital Burn Unit and resuscitated with a modified Parkland formula. Plasma was drawn on admission, at 12, 24, and 48 hours. Endothelin-1 and PGE2 were measured by radioimmunoassay. RESULTS: Endothelin-1 levels increased ten- to 20-fold in all patients. Prostaglandin E2 levels increased five- to 40-fold in all patients. There was no correlation between plasma ET-1 or PGE2 levels with either size of burn, inhalation injury, patient age, organ dysfunction, or survival in this small study of early burn injury. CONCLUSIONS: The increased plasma ET-1 response in patients with burns may have a role in the genesis of the systemic response to burns. This peptide may also activate monocyte production of PGE2 and other mediators of the systemic inflammatory response syndrome. This study was done to measure ET-1 and PGE2 levels in patients with burns greater than 20 percent of the body surface area on admission, at 12, 24, and 48 hours. The correlations between severity of burn, ET-1 levels, and PGE2 production were also assessed. PMID- 7874343 TI - A multicenter study of phospholipase A2 in patients in intensive care units. AB - BACKGROUND: Multiple organ failure (MOF) is becoming the most common cause of death in patients in surgical intensive care units. In this respect, a multicenter study in four different groups of patients in surgical intensive care units was done to evaluate the role of phospholipase A2 (PLA2) in comparison with C-reactive protein (CRP) and polymorphonuclear (PMN) elastase. STUDY DESIGN: A total of 223 patients entered the study: 73 patients with multiple injuries, 46 patients with diffuse peritonitis, 52 patients with sepsis, and 52 patients in a control group who were at a higher risk for postoperative sepsis after defined surgical interventions. The patients underwent a daily monitoring of PLA2, CRP, and PMN elastase for seven days. RESULTS: Phospholipase A2 activity remained within the normal range in patients with multiple injuries and patients in the control group, indicating that this parameter is not influenced by the postaggression metabolism. In contrast, in patients with peritonitis, high PLA2 values were found from the beginning. The efficiency for predicting a lethal MOF was 85 percent for PLA2 (cut-off 80 U/L) in patients if determined at the day of operation. A comparably favorable efficiency (84 percent) was demonstrated for PMN elastase in patients with multiple injuries (cut-off 205 micrograms/L) measured at day one. CONCLUSIONS: These efficiency rates of PLA2 in peritonitis and PMN elastase in multiple injuries were comparable or even better than multifactorial scoring systems used in the study. C-reactive protein did not contribute to an early estimation of the prognosis in all groups analyzed. Therefore, the measurement of PLA2 in patients with diffuse peritonitis and PMN elastase in patients with multiple injuries, as single parameters, is recommended to estimate the individual risk for the occurrence of lethal MOF. PMID- 7874344 TI - Peter Brian Medawar: father of transplantation. PMID- 7874345 TI - Emergency shunt for variceal bleeding. PMID- 7874346 TI - Toxic epidermal necrolysis: a systemic and dermatologic disorder best treated with standard treatment protocols in burn intensive care units without the prolonged use of corticosteroids. PMID- 7874347 TI - An improved technique for the placement of hemodialysis catheters in the internal jugular vein. PMID- 7874348 TI - Operative correction of pectus excavatum using the right ventricle as a sternal support. PMID- 7874349 TI - A technique of removal of the Tenckhoff peritoneal dialysis catheter. PMID- 7874350 TI - Three-segmental cytodiagnosis using balloon catheter for locating occult carcinoma of the pancreas. PMID- 7874351 TI - Halsted and "the vibrant domain of surgery". PMID- 7874352 TI - General operative aspects of human immunodeficiency virus infection and acquired immunodeficiency syndrome. PMID- 7874353 TI - Diagnosis and natural history of extramammary tumors metastatic to the breast. PMID- 7874354 TI - Post-traumatic empyema. PMID- 7874355 TI - Stress in doctors: not so simple solutions. PMID- 7874356 TI - What's new in temporary pacing? PMID- 7874357 TI - Retrieval of spilled stones during laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy is now widely practised in the Western world. One of the more common and often neglected complications is perforation of the gallbladder and spillage of bile and stones. With careful attention to technique this should be a rare complication. The effect of bile and stone spillage may depend on the presence or absence of biliary infection at the time of operation. When stone spillage occurs a number of options are available for the retrieval of stones and these are highlighted in this paper. PMID- 7874358 TI - Epiglottitis: a disease of all ages. AB - Epiglottitis is an acute life-threatening infectious condition characterised by local supraglottic inflammation. Although it is predominantly a disease of childhood, it occurs in all age groups. The risk of sudden complete airway obstruction necessitates careful monitoring, prompt responses and clinical expertise in airway management. PMID- 7874359 TI - Prognostic role of the perinatal postmortem. AB - Perinatal autopsy plays an invaluable role in the overall management of the unsuccessful pregnancy. In addition to the accurate identification of malformations, inherited disorders and acquired diseases, it also allows the exclusion of such diagnoses. Positive and negative findings are equally important in the counselling of parents. PMID- 7874360 TI - Pharmacology of local anaesthetic agents. AB - Local anaesthetic agents are widely used throughout medicine and dentistry. The profiles of the different members of this group of drugs vary considerably, so that an understanding of the pharmacology of these agents is essential if they are to be used safely. PMID- 7874361 TI - Treatment of polymyositis and dermatomyositis. AB - Polymyositis and dermatomyositis are serious inflammatory muscle disorders which may present life-threatening complications. It is important to recognise and treat the condition in the early stages of the disease. Corticosteroids remain the mainstay of treatment, and their resistance and other forms of immunotherapy are discussed. PMID- 7874362 TI - Significance of anogenital warts in children. AB - Abuse or non-abuse, that is the question? The possibility of sexual abuse must be considered in every child with anogenital warts. However, innocent transmission of infection is recognised. This article sets out the evidence and indicates the points that should be addressed in order to identify the significance of anogenital warts in each child. PMID- 7874363 TI - Antibiotic resistance: the current position and the molecular mechanisms involved. AB - The introduction of antibiotics heralded a new era in the chemotherapy of infectious diseases, but over the ensuing years bacterial evolutionary responses to the selective pressure of antibiotics have resulted in microorganisms resistant to virtually every known antibiotic. The consequences have been very important in clinical practice, as patients infected with a multi-resistant organism suffer increased morbidity and mortality and often require the use of expensive and potentially toxic antibiotic regimens in order to achieve effective, specific treatment. PMID- 7874364 TI - A case of polaroid photographs being used during an operation to discuss unforeseen findings with the next-of-kin. PMID- 7874365 TI - Accreditation of psychotherapists: what and how? PMID- 7874366 TI - Accreditation of psychotherapists: what and how? PMID- 7874367 TI - Turning water into wine. PMID- 7874368 TI - Coexisting laryngeal trauma and cardiac tamponade. PMID- 7874369 TI - Effects of flupirtine coadministration on phenprocoumon plasma concentrations and prothrombin time. AB - The influence of flupirtine, a non-opioid, centrally acting analgesic agent on phenprocoumon plasma levels and protein binding as well as prolongation of prothrombin time has been investigated in 12 healthy male volunteers. Subjects received phenprocoumon 1.5 mg od over 28 days. From day 15 to 28 oral flupirtine 100mg tid was added. Phenprocoumon plasma levels and prothrombin time (Quick time), measured at trough before the morning drug intake, were chosen as primary pharmacokinetic and pharmacodynamic variables. In addition, phenprocoumon protein binding and the eudismic ratio of phenprocoumon were determined. The mean values from data obtained on day 12 to 15 (i.e. measurements under phenprocoumon alone) and the mean values from those data obtained from day 25 to 28 (i.e. under comedication with flupirtine) were subject to subsequent statistical procedures. Phenprocoumon plasma concentrations came to 1.38 +/- 0.28 micrograms/ml on day 12 to 15 and were not significantly altered under flupirtine coadministration with 1.48 +/- 0.36 micrograms/ml on day 25 to 28 (95% confidence interval: 1.02-1.11, point estimator: 1.06). The average Quick time came to 68 +/- 10% on day 12-15 and 73 +/- 15% on day 25-28. The nonparametric 95%-confidence interval for the ratio ranged between 0.96 and 1.14, the point estimator was determined to 1.04. Protein binding of phenprocoumon was determined to 88.8% +/- 0.5 on day 14 and to 88.9 +/- 0.5% on day 28. The ratio of S/R-phenprocoumon was 1:0.84 on day 14 and 1:0.84 on day 28. These results do not provide any evidence for a pharmacokinetic and/or pharmacodynamic interaction between flupirtine and phenprocoumon. PMID- 7874370 TI - COMT inhibition by high-dose entacapone does not affect hemodynamics but changes catecholamine metabolism in healthy volunteers at rest and during exercise. AB - We studied the effects of catechol-O-methyltransferase (COMT) inhibition with entacapone on hemodynamics and catecholamine metabolism in healthy volunteers at rest and during a bicycle exercise test. Entacapone was given orally during two periods of seven days each to eleven healthy male volunteers; on the first period 400 mg t.i.d. and on the second 800 mg t.i.d. A submaximal exercise test giving a heart rate of about 163-167 beats/min with the highest predetermined work load was performed on a bicycle ergometer, and blood pressure, heart rate and ECG were recorded. The concentrations of adrenaline, noradrenaline, 3,4 dihydroxyphenylglycol (DHPG), 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4 dihydroxyphenylacetic acid (DOPAC) in plasma were determined. Blood pressure, heart rate, ECG, and plasma concentrations of unconjugated adrenaline and noradrenaline were not influenced after single and repeated dosing of entacapone. The plasma concentrations of DHPG (a monoamine oxidase (MAO)-dependent metabolite) increased maximally by 245% compared to the control day. DOPAC (a MAO dependent metabolite) increased maximally by 144% and MHPG (a COMT-dependent metabolite) decreased by 54%. The increase in DHPG and DOPAC was significantly greater with the 800 mg dose than with the 400 mg dose. The decrease in MHPG was significantly greater with the repeated dosing than with the single dose of entacapone. COMT inhibition by entacapone seems not to affect hemodynamics or plasma concentrations of unconjugated adrenaline and noradrenaline in healthy volunteers either at rest or during exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874371 TI - Interdepartmental graduate studies in clinical pharmacology: a practical model. AB - The discipline of Clinical Pharmacology serves many purposes and plays a critical role in therapeutic education, especially in a medical school. An effective program bridges the gap between basic pharmacology and clinical practice. A clinical pharmacology program must provide the student with the necessary information to employ the basic pharmacology knowledge gained in formatting a successful therapeutic plan. The program is built around the student and brings together the best to be offered in 2 or more disciplines; it requires diverse disciplines to work together in a variety of departments and centers which cut across disciplinary lines. In order to facilitate this interaction, the Division of Clinical Pharmacology at the University of Miami embarked on establishing a Ph.D. program with an emphasis on Clinical Pharmacology utilizing an already established unique program referred to as "Interdepartmental Graduate Studies". To enter the structured Ph.D. program the students must be among the fellowship awardees of the Interdepartment Graduate Studies Program, which is administered by social committees with specific roles, directions and guidelines. The students follow the general requirements of the Ph.D. degree set forth by the graduate school. Students attend formal classes tailored to their program of interest based on the committee's recommendations in the respective departments involved. The significance of this program is that it can be tailored to fit individual areas of interest leading to a well-developed researcher who is neither overspecialized nor undereducated and able to make rational decisions in an age of multiple therapies. PMID- 7874372 TI - Treatment of clinical rabies in man: drug therapy and other measures. AB - The treatment of symptomatic rabies is a challenging problem; no specific drug is yet available. Isolation in intensive care unit with symptomatic and supportive measures is the mainstay of treatment at present. Antiviral drugs, particularly interferon and interferon-inducers, have been employed with variable results. Corticosteroid is not effective. Anti-rabies vaccine has no proven efficacy in treatment. Effective treatment of systemic complications during survival period with appropriate therapy is essential. PMID- 7874373 TI - TAME-esterase activity during a prolonged attack of asthma. AB - We measured serum N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity in a group of patients suffering from a prolonged attack of asthma. Measurements were made pre and post salbutamol nebulization. Our results showed that TAME esterase activity did not change significantly pre or post nebulization. Based on our experimental data, we concluded that increase serum TAME-esterase activity is a biochemical substance associated with the early asthmatic response but not with prolonged attack of asthma. PMID- 7874374 TI - Comparison of the onset, spontaneous recovery and train of four fade of the clinical neuromuscular block produced by pancuronium and pipecuronium. AB - The following study was performed to delineate the possible differences in the onset, recovery and "train of four" (TOF) fade characteristics of pancuronium (Pan) and pipecuronium (Pip). Eighty adult American Society of Anesthesiologists (ASA) class I and II surgical patients were studied with institutional approval. After premedication, general anesthesia was induced with thiopental sodium i.v. followed by N2/O2 halothane and fentanyl. The lungs were ventilated. Normocarbia and normothermia were maintained. Two groups of 40 patients received pancuronium (0.1 mg/kg i.v.) or pipecuronium (0.07 mg/kg i.v.). Neuromuscular block (NMB) was measured simultaneously by mechanomyography (MMG) and electromyographically (EMG) on the thumb adductor muscle. Supramaximal (TOF) stimuli were applied to the ulnar nerve every 20 seconds. The onset of neuromuscular blocking action, duration of action (to 25% recovery of twitch response). TOF fade during onset and up to 25% T1 response recovery, hemodynamic changes following induction of anesthesia and after the muscle relaxant and subsequent oral intubation were determined. Mean values and the differences in the two treatments groups were statistically analyzed. The onset of action of the two agents were similar: 3.62 +/- 0.02 minutes (MMG) and 4.94 +/- 0.05 minutes (EMG, Pan) and 3.74 +/- 0.02 minutes (MMG) and 4.36 +/- 0.012 minutes (EMG, Pip). TOF fade ratios during the onset phase were similar. TOF fade at the 25% twitch responses recovery level was 100% with the MMG responses and (96% (Pan) and 94.8% (Pip) with the EMG responses at the 25% twitch response recovery level. Hemodynamic changes were similar after the single dose administration of the bolus administration of the two NMB agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874375 TI - Fixed combination of benazepril and very low dose hydrochlorothiazide in the treatment of mild to moderate essential hypertension: evaluation by 24-hour non invasive ambulatory blood pressure monitoring. AB - A double-blind, crossover, placebo-controlled study was undertaken in order to assess the antihypertensive efficacy of a fixed combination of benazepril and hydrochlorothiazide in two different dosages by ambulatory blood pressure monitoring (ABPM). After a three-week placebo wash-out period, 18 patients with mild to moderate essential hypertension, all males, aged 41-60 years, were randomized to receive benazepril 5 mg + hydrochlorothiazide 6.25 mg, benazepril 10 mg + hydrochlorothiazide 12.5 mg or placebo, all given once daily for 4 weeks, according to a 3 crossover period, arranged in a 3 x 3 latin square design. Patients were checked after the wash-out period and every 4 weeks thereafter. At each visit, 24-hour ABPM was performed by a non-invasive device (Spacelabs 90202); causal BP (by mercury sphygmomanometer) and HR were also measured. Both dosages of the fixed combination were equally effective in reducing systolic and diastolic BP values throughout the 24-hour period as compared to the placebo. The antihypertensive effect of the drug could be observed to a similar extent both during the day and night and was still significant 24-hour post-dosing. In addition, the fixed combination did not affect the normal BP circadian variability. PMID- 7874376 TI - Severe generalized hyperkinesia to nicardipine SR therapy. AB - A patient who was taking nicardipine SR for angina management suffered two episodes of severe involuntary tonic and clonic muscular contractions, involving both upper extremities and torso without loss of consciousness. This tardive dyskinesia occurred in the absence of hypotension and cardiac rhythm disorder. Intravenous diazepam promptly controlled these symptoms. The precise etiology of the dyskinesia is not clear and its relation to nicardipine remains speculative as the patient refused rechallenge with the drug. Possible hypothesis for tardive dyskinesia and nicardipine are presented. PMID- 7874377 TI - Plasma concentrations of free and conjugated silybin after oral intake of a silybin-phosphatidylcholine complex (silipide) in healthy volunteers. AB - The plasma concentrations of free (unconjugated) and conjugated silybin after intake of a single oral dose of a lipophilic silybin-phospatidylcholine complex (silipide, 80 mg expressed as silybin equivalents) were evaluated in 12 healthy volunteers by using a sensitive and specific HPLC method. Free silybin concentrations reached a peak of 141 +/- 31 ng/ml (mean +/- SEM) at 2.4 hours after dosing and declined thereafter with a half-life of about 2 hours. Peak concentrations of conjugated silybin were greater (255 +/- 35 ng/ml) and occurred at a later time (about 3.8 hours). The elimination of conjugated drug tended to be slower than that of free drug. AUC values for conjugated sylibin were about three-fold greater than those of free drug. It is concluded that after oral intake of silipide, silybin undergoes extensive conversion to conjugated derivative(s) which are retained in the circulation at relatively large concentrations. PMID- 7874378 TI - In vivo binding characteristics of carbamazepine and carbamazepine 10, 11-epoxide to serum proteins in monotherapy adult patients. AB - The in vivo serum protein binding characteristics of carbamazepine and carbamazepine 10, 11-epoxide, which was the main metabolite of carbamazepine in plasma, were assessed in sera from 30 adult patients with epilepsy on carbamazepine monotherapy. The binding characteristics of each compound were analyzed according to the two-site binding model. Association constants to the high-affinity binding site on alpha 1-acid glycoprotein (AAG) were 0.053 l/mumol for carbamazepine and 0.013 l/mumol for carbamazepine 10, 11-epoxide. The maximum binding capacities for drug-AAG binding were 49.2 mumol/l for carbamazepine and 48.1 mumol/l for carbamazepine-10, 11-epoxide. The products of the association constant and binding capacity for the lower-affinity site (i.e., the linear component of albumin binding site) were 1.273 for carbamazepine and 0.525 for carbamazepine 10, 11-epoxide. Within the total concentration range of each compound investigated, the contribution of drug-AAG binding to the total serum binding was relatively larger than that of drug-albumin binding. PMID- 7874379 TI - Pharmacokinetics of ethyl biscoumacetate and its metabolite 7-hydroxy ethyl biscoumacetate in healthy volunteers. AB - Disposition kinetics of ethyl biscoumacetate and its metabolite 7-hydroxy ethyl biscoumacetate were evaluated in ten healthy volunteers, after a single 300 mg oral dose of ethyl biscoumacetate. Serum concentrations of parent compound and its metabolite were measured by HPLC. The maximum serum ethyl biscoumacetate concentrations were reached 1.0-4.0 hours after drug dosing. From 3 hours after drug administration the concentration of the metabolite was always higher than the concentration of the parent compound. Geometric mean of elimination half-life was 0.66 hours for ethyl biscoumacetate and 2.03 hours for the 7-hydroxy ethyl metabolite. PMID- 7874380 TI - The design of oral sustained-release theophylline dosing after conversion from intravenous to oral therapy. AB - We studied the design of oral sustained-release theophylline dosing after conversion from constant aminophylline infusion. Twelve children with bronchial asthma (9 boys and 3 girls) were evaluated in this study. Each patient received a constant intravenous administration of aminophylline for 4-10 days. Three hours after conversion from constant aminophylline infusion, they received oral sustained-release theophylline twice daily at 12-hour intervals. Blood samples were obtained at least once during the aminophylline infusion, just before conversion from the aminophylline infusion, and 0, 3 and 6 hours, and 4-5 days after administering oral theophylline. Pharmacokinetic parameters were estimated using the serum theophylline concentrations that were obtained during constant aminophylline infusion. These estimates of pharmacokinetic parameters were used to predict the serum theophylline concentrations during oral theophylline therapy. Predicted serum theophylline concentrations using individual pharmacokinetic parameters were fitted with actual measured values in this study. When switching a patient from intravenous aminophylline to sustained-release oral theophylline, the use of Bayesian analysis of serum theophylline concentration values obtained during intravenous therapy works well in predicting serum theophylline concentrations and in determining oral dosages that maximize the drug's effectiveness. PMID- 7874381 TI - Neuro-AIDS. Proceedings of a workshop. Portland, Maine, August 16-19, 1993. PMID- 7874382 TI - Summary of workshop contributions. Third Workshop on NeuroAIDS. PMID- 7874383 TI - gp120 as an etiologic agent for NeuroAIDS: neurotoxicity and model systems. AB - The search for an agent that can mediate the symptoms of NeuroAIDS has been directed at gp120, the major envelope protein from HIV. The toxicity associated with gp120 was examined as a model and predictor of the neuropathological and neuropsychiatric manifestations of AIDS. Studies of the neurotoxic effects of purified gp120 on neurons from the rodent CNS cell cultures indicated the following: potent and selective killing of subpopulations of hippocampal neurons; varying potency of gp120s obtained from various HIV isolates; complete and potent protection from gp120 killing action after treatment with peptides related to vasoactive intestinal peptide; and obligatory presence of glia for gp120-related toxicity. Investigations of gp120 treatment of rodents revealed: cortical neurodystrophy with reduced arborizations and swollen processes; delays in developmental behaviors involving motor skills; peptide T prevention or attenuation of the morphological and behavioral deficits/delays produced by administration of gp120; and impairment of learning in the Morris swim maze. In addition, studies of subcutaneously administered, radiolabeled gp120 in neonatal animals demonstrated the presence of toxic fragments of gp120 in the developing brain. With the use of model test systems of non-human derived cell cultures and neonatal rats, we have captured and predicted a number of the morphological and behavioral deficits associated with AIDS. These multi-disciplinary studies of the actions of gp120 and associated fragments in rodents and rodent cells predict that the loss of cognitive and neurological function in patients with AIDS are attributed in part to interference of critical brain functions by the envelope protein, gp120. PMID- 7874384 TI - gp120-mediated alterations in astrocyte ion transport. AB - The pathogenesis of the acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) is unknown. However, recent work indicates that neurons and astrocytes are functionally compromised by exposure to viral components or cellular factors released from HIV-1-infected macrophages/microglia. We show that exposure of primary cultured rat astrocytes to the major HIV envelope glycoprotein gp120 results in alterations of ion and solute transport that may contribute to neuronal cell injury. PMID- 7874385 TI - Update on current models of HIV-related neuronal injury: platelet-activating factor, arachidonic acid and nitric oxide. AB - This review aims to summarize recent work related to the pathogenesis and possible treatment of neuronal injury in the acquired immunodeficiency syndrome (AIDS), especially with reference to potential neurotoxic substances released by HIV-infected or gp120-stimulated macrophages/microglia. Approximately a third of adults and half of children with AIDS eventually suffer from neurological manifestations, including dysfunction of cognition, movement, and sensation. Among the various pathologies reported in brains of patients with AIDS is neuronal injury and loss. A paradox arises, however, because neurons themselves are for all intents and purposes not infected by human immunodeficiency virus type 1 (HIV-1). This paper reviews recent evidence suggesting that at least part of the neuronal injury observed in the brains of AIDS patients is related to excessive influx of Ca2+ after the release of potentially noxious substances from HIV-infected or gp120-stimulated macrophages/microglia. There is growing support for the existence of HIV- or immune-related toxins that lead indirectly to the injury or demise of neurons via a potentially complex web of interactions between macrophages (or microglia), astrocytes, and neurons. HIV-infected monocytoid cells (macrophages, microglia or monocytes), especially after interacting with astrocytes, secrete substances that potentially contribute to neurotoxicity. Not all of these substances are yet known, but they may include eicosanoids, i.e. arachidonic acid and its metabolites, as well as platelet-activating factor. Other candidate toxins include nitric oxide (NO.), superoxide anion (O2.-), and the N-methyl-D-aspartate (NMDA) agonist, cysteine. Similarly, macrophages activated by HIV-1 envelope protein gp120 also appear to release arachidonic acid and its metabolites, and cysteine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874386 TI - An experimental model system for HIV-1-induced brain injury. AB - The pathological hallmark of HIV infection in brain is productive viral replication in cells of mononuclear phagocyte lineage including brain macrophages, microglia and multinucleated giant cells (Koenig et al., 1986; Wiley et al., 1986; Gabuzda et al., 1986; Stoler et al., 1986). These cells secrete viral and cell encoded neurotoxins that lead to neuronal injury, glial proliferation and myelin pallor during advancing disease (Genis et al., 1992; Giulian et al., 1990, 1993; Pulliam et al., 1991). The apparent paradox between the distribution and numbers of virus infected cells and brain tissue pathology support indirect mechanisms for CNS damage (Epstein, 1993; Geleziunas et al., 1992; Merrill and Chen, 1992; Michaels et al., 1988; Price et al., 1988). First, brain macrophages and microglia can produce neurotoxins by secretion of viral proteins (for example, gp120) (Dawson et al., 1991; Merrill et al., 1989; Lipton et al., 1990; Lipton, 1993). Second, HIV primes macrophages for immune activation to produce neurotoxins including: cytokines (TNF alpha and IL-1 beta), eicosanoids: quinolinate and nitric oxide (NO). Chronic immune stimulation mediated by opportunistic infections and chronic interferon gamma (IFN gamma) production (in and outside the CNS) continues the process of macrophage activation leading to progressive neural injury. The hyperresponsiveness of HIV infected macrophages to activation results in production of cellular factors that activate uninfected macrophages. This suggests that HIV-infected macrophages are both perpetrators and amplifiers for neurotoxic activities. PMID- 7874387 TI - Investigation of HIV-infected macrophage neurotoxin production from patients with AIDS dementia. AB - The mechanism for AIDS dementia may involve the production of toxic cytokines. Since macrophage/microglia are the infected cells in the brain, we were interested in the production of some of the same cytokines by HIV-infected macrophages from patients with AIDS dementia. HIV-infected macrophages from 11 patients with AIDS dementia were cultured and evaluated for p24, cytomegalovirus (CMV) DNA, and the production of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF alpha) and other neurotoxic factors. The percentage of HIV macrophage infectivity did not correlate with the severity of dementia nor did the presence of CMV. The production of IL-6 and an unidentified neurotoxin did not correlate with HIV macrophage infectivity suggesting that these soluble factors are strain specific. Production of TNF alpha by HIV-infected macrophages was relatively low (< 1-35 pg/ml) and may not be a significant factor in toxicity. PMID- 7874388 TI - Cytokine dysregulation in HIV-associated neurological disease. AB - AIDS is associated with three major neurological syndromes: dementia (HIVD), vacuolar myelopathy (VM) and plainful sensory neuropathy (PSN). The pathogenesis of these conditions remains unclear although they all demonstrate a marked increase in macrophage number and activation despite systemic immunosuppression. It was therefore of interest to determine the profile of cytokine and HIV expression in brain, spinal cord and peripheral nerves of AIDS patients with AD, VM and PSN, as compared to AIDS patients without neurological disease and seronegative controls. RNA was extracted from brain, spinal cord and peripheral nerve and RT/PCR for cytokine and HIV mRNA was performed. In situ RT/PCR was performed to determine the number and type of cells expressing cytokine message and this was compared to the number of cells containing HIV DNA detected with in situ PCR. We found a consistent profile of increased TNF alpha and decreased IFN gamma and IL4 in all three syndromes compared to AIDS patients without neurological disease. IL1 did not increase in parallel with TNF alpha IL10 was decreased in the VM tissue. HIV transcripts were increased in the AD brains compared to non-demented controls but were detected only occasionally in spinal cord and not at all in peripheral nerve. Preliminary data from in situ RT/PCR suggests that a large number of cells are expressing. TNF alpha but only a small number are infected with HIV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874389 TI - Clinical comparison of adult and pediatric NeuroAIDS. AB - Human Immunodeficiency Virus type-1 (HIV-1)-associated neurologic disease occurs as the initial presenting clinical manifestation of acquired immunodeficiency syndrome (AIDS) in 3-7% of infected patients, but in up to 18% of children and adolescents (Janssen, 1992; Janssen et al., 1992; Scott et al., 1989; Mintz et al., 1989a; Epstein et al., 1986). The overall prevalence of dementia in adult AIDS patients is 7.3-11.3% (Janssen, 1992), but up to 30-60% of children with AIDS manifest an analogous progressive encephalopathy (Epstein et al., 1986; Belman et al., 1988; Mintz, 1992; The European Collaborative Study, 1990). As a result of both direct and indirect effects of HIV-1 infection of the central nervous system (CNS), a distinct clinical and pathologic picture has emerged of insidious and severe neurologic deterioration, termed "AIDS Dementia Complex" (ADC) in adults, and "HIV-1-associated Progressive Encephalopathy" (PE) in children (Working Group, 1991) (see Table 1). In the severe manifestations of this pariah, there is little dispute as to the necessity of CNS HIV-1 infection for precipitating the cascade of adverse neurologic symptoms, although the pathogenic mechanisms of neurologic dysfunction and destruction--whether a result of direct cellular infection of HIV, secondarily produced and upregulated cytotoxic cytokines, or co-infection with opportunistic pathogens--remains an area of active research (Epstein and Gendelman, 1993; Fiala et al., 1993; Wiley and Nelson, 1988; Saito et al., 1994; Koenig et al., 1986; Sharer, 1992). Furthermore, the existence of systemic immune deficiency renders the CNS susceptible to opportunistic infection (OI), particularly in adult patients, adding further to morbidity and mortality (Clifford and Campbell, 1992). With the introduction of antiretroviral nucleoside analogues, there have been reports of a decreasing incidence of ADC (Portegies et al., 1989; Day et al., 1992), and amelioration--at least temporarily--of PE in children (Pizzo et al., 1988; Mintz and Epstein, 1992; Brouwers et al., 1990; Mintz et al., 1990). This appends further evidence to the central precipitating role of CNS HIV-1 infection. PMID- 7874390 TI - Interrelations among patterns of change in neurocognitive, CT brain imaging and CD4 measures associated with anti-retroviral therapy in children with symptomatic HIV infection. AB - The interrelationships of patterns of change and variability between baseline and after 6 months of anti-retroviral therapy in neurocognitive, brain imaging, and immune measures were studied in 77 children with symptomatic HIV disease. Overall improvement in CNS structure/function after 6 months of anti-retroviral therapy was limited; new intracerebral calcifications tended to occur and old ones tended to progress in young children with vertically acquired HIV infection, despite treatment. Substantial inter-individual differences in change were however observed. Factors which explained part of the variance in the magnitude and direction of change were baseline structural and functional abnormalities, rating of degree of CNS penetration of the drug protocol, and concurrent changes on other variables. These preliminary data suggest that CNS specific effects of therapies as well as pretreatment status of CNS function/structure need to be taken into consideration when evaluating future trials of anti-retroviral therapy for children with symptomatic HIV infection. PMID- 7874391 TI - Effects of chronic zidovudine administration on CNS function and virus burden after perinatal SIV infection in rhesus monkeys. AB - Continuous intravenous administration of zidovudine (AZT) has been reported to improve cognitive function in HIV-infected pediatric patients (Pizzo et al., 1988). The effects of long-term zidovudine treatment in the perinatally infected pediatric population, including antiviral efficacy and effects on cognitive and motor function has not been systematically examined. These questions were addressed in rhesus macaque infants infected at birth with SIVSMM/B670, a primate model for infantile HIV infection and disease (Eiden et al., 1993a). Continuous or intermittent administration of AZT during the first 6 months following infection resulted in about a doubling of lifespan, a delay in the occurrence of motor impairment, and lower virus burden and quinolinic acid levels in cerebrospinal fluid (CSF) following administration of the antiviral drug. PMID- 7874392 TI - Human neural xenografts: progress in developing an in-vivo model to study human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) infection. AB - Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. In order to study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11-17.5 weeks) human fetal brain or neural retina is transplanted into the anterior chamber of the eye of immunosuppressed adult rats (Epstein et al., 1992; Cvetkovich et al., 1992), and more recently in immunodeficient (SCID) mice. The human xenografts survive for many months, vascularize and form a blood-brain barrier. Immunohistochemistry with PGP 9.5 identified neuronal cell bodies and neuritic processes. Electron microscopy revealed axonal growth cones and synaptic junctions. Infection of these xenografts with cell-free HIV-1 proved difficult, however co-engraftment with HIV-1-infected human monocytes resulted in characteristic pathological changes, including the formation of syncytial giant cells, neuronal loss, and astroglial proliferation, supporting the hypothesis that these cells can mediate neurotoxicity. In other studies, xenografts of human fetal retinal tissue were readily infected with cell-free human cytomegalovirus (HCMV) strain AD169. These grafts contained cells with intracytoplasmic and intranuclear inclusions typical of HCMV infection. Productive infection within these grafts was demonstrated by the presence of immediate early, and late (capsid) HCMV antigens, by recovery of HCMV on human fibroblast cultures, and by serial passage of virus to additional retinal xenografts (DiLoreto et al., 1994).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874393 TI - In vivo model of HIV infection of the human brain. AB - Approximately one quarter of AIDS patients develop neurologic symptoms attributable to HIV infection within the brain. Previous studies suggest that HIV associated neurologic damage may be mediated by immune factors secreted by activated/infected CNS macrophages. We developed an in vivo system in which human embryonic brain tissue can be infected with HIV and the associated pathology monitored. In this model, dissociated human brain tissue is grown in vitro as single cell suspension in serum free medium. Fetal neural cells aggregate and form "brain microspheres" that are then transplanted into SCID mice. Pilot studies suggest that brain microspheres injected in the fat pad of SCID mice differentiate and survive for several months in vivo. Study of these grafts shows presence of functional neural cells and vascular organization suggesting a blood brain barrier. When brain microspheres are co-cultured in vitro with HIV-infected human macrophages, virus is detected inside the human neural tissue grafts in SCID mice and measurements of viral and immune factors can be performed. To promote physiologic neuronal differentiation within the human grafts, implantation in the brain of SCID mice is being tested at the present time. PMID- 7874394 TI - Neuronal substrates for SIV encephalopathy. AB - Prior to the onset of immunodeficiency disease, neurochemical and neuropathological events associated with motor and/or cognitive impairment can be identified in rhesus monkeys infected with simian immunodeficiency virus (SIV). These are astrocytosis, up-regulation of mRNA encoding the neuropeptide somatostatin (SRIF) and an increased expression of MHC Class II antigen. End stage immunodeficiency disease has been associated with robust viral expression in the CNS frequently observed as multinucleated giant cell formation. SIV encephalitis has not been observed in animals whose only clinical signs of SIV disease were motor and/or cognitive impairment. These data suggest that neuronal dysfunction discernable as altered neuropeptide expression in cortical neurons precedes frank structural damage to the CNS in SIV encephalopathy. This model is consistent with the mechanism of neuropathogenesis in human HIV encephalopathy that can be partially inferred from neurochemical and neuropathological examination of autopsy material in HIV disease. PMID- 7874395 TI - Immune regulatory and effector properties of human adult microglia studies in vitro and in situ. AB - Monocytes, macrophages, and brain microglia are the primary cell types most readily demonstrated to be infected in CNS lesions of patients infected with HIV (Koenig et al., 1986). Microglia are implicated in mediating CNS immune regulation and neural tissue injury associated with the AIDS-dementia syndrome. This report describes the isolation and characterization of microglia from the adult human central nervous system (CNS), and the assessment of microglial immune accessory/effector functions, some of which might be altered in CNS infectious and autoimmune diseases. In our studies we have compared the in vitro properties of microglia with peripheral blood monocytes/macrophages, and with astrocytes, a CNS cell type also implicated in contributing to immune regulatory and effector functions. Additionally, we have compared phenotypic features of resident microglia in situ with monocytes and macrophages that have infiltrated the CNS during the course of CNS inflammation. Our results suggest that adult human derived parenchymal microglia represent a unique cell of monocytic origin that can be distinguished both in vitro and in situ from monocytes/macrophages recently infiltrating into the CNS and from perivascular macrophages/microglial cells. Our data demonstrate that parenchymal microglia express several immune accessory/adhesion molecules that can provide second signals for CD4+T cell stimulation. Furthermore, microglia can synthesize cytokines and reactive oxygen species that may augment ongoing pathology in the CNS of AIDS patients. Infection of resident brain microglia could augment microglial immune accessory/effector functions possibly contributing to pathology seen in HIV dementia. PMID- 7874396 TI - Detection of HIV-1 DNA in pediatric AIDS brain tissue by two-step ISPCR. AB - In order to detect latent infection in neurons or other cell types in formalin fixed brain tissue, we performed polymerase chain reaction amplification with incorporation of digoxigenin-conjugated deoxynucleotides, followed by in situ hybridization with biotinylated probes. The use of this two-step technique in brain tissue from a child with severe HIV-1 encephalitis revealed signal in both nuclear and perinuclear regions of cells identified as monocytes and astrocytes, and also in perineuronal satellite cells of glial morphology, but HIV-1 infection of neurons was not detected. PMID- 7874397 TI - In vivo and in vitro infection of the astrocyte by HIV-1. PMID- 7874398 TI - Activation of HIV-1 transcription by Tat in cells derived from the CNS: evidence for the participation of NF-kappa B--a review. AB - Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of acquired immune deficiency syndrome (AIDS). The Tat protein of HIV-1 is a potent activator of transcription directed by the viral long terminal repeat. It has been widely reported that this activation requires a specific interaction between Tat and a RNA target termed TAR in the 5'-leader sequence of HIV-1 mRNAs. In this report we present data and describe results which illustrate that under appropriate conditions activation of transcription by Tat occurs independent of the TAR element. The ability to mediate TAR-independent transactivation by Tat is constitutive in some central nervous system cells and requires prior activation in others such as T lymphocytes. Evidence implicating a specific transcription factor in mediating Tat activation is also presented. Studies with site-directed mutants demonstrate that the RNA-binding domain of Tat is dispensable for TAR independent activation of HIV-1. In contrast, the requirement for specific components of the Tat activation domain suggests that common targets exist for this viral activation factor to exert its activity in TAR-independent and TAR dependent transactivation pathways of HIV-1 transcriptional activation. A working model of TAR-independent transactivation, which we believe may be responsible for the activation of cellular genes which contribute to AIDS pathology, is presented. PMID- 7874399 TI - Neuroglial-specific factors and the regulation of retrovirus transcription. AB - Retroviruses have been implicated as causative agents of a variety of human diseases including malignancy, immune system dysfunction, and neurologic disorders. Despite the isolation of various retroviral agents from patients suffering from malignant neoplasias and neurologic disorders, only the human T cell lymphotropic virus type I (HTLV-I) and the human immunodeficiency virus (HIV) have been definitively accepted as etiologic agents of human disease (Hjelle, 1991; Gessain and Gout, 1992; Rosenblatt, 1993). Because of their increasingly defined roles in disease progression, the replication of HTLV-I and HIV is an important focus for understanding the pathogenic processes resulting from viral infection. Of particular interest are the molecular mechanisms by which expression of retroviral genomes is regulated by their regulatory units, the long terminal repeats (LTR), in a manner specific to the cellular targets which they infect. PMID- 7874400 TI - Measurement of CNS HIV burden and its association with neurologic damage. AB - AIDS dementia complex affects between 20 and 30% of terminally ill AIDS patients. The histopathologic substrate of this clinical syndrome is chronic HIV infection of the nervous system termed HIV encephalitis. We hypothesize that the abundance and length of time that HIV is present in the CNS determines the severity of neurologic damage. We compared three different methods of assessing HIV burden in the CNS. While the assays vary in sensitivity, each provides a quantitative estimate of viral burden that can be compared between laboratories. Assays of provirus were readily divided into two groups, while protein assays showed a wider range. HIV-mediated neurotoxicity might be expected to more closely depend upon productive infection. PMID- 7874401 TI - CMV-specific immune responses and HLA phenotypes of AIDS patients who develop CMV retinitis. HNRC Group. HIV Neurobehavioral Research Center. AB - HLA phenotype and immune responses to CMV were studied to determine whether the subset of AIDS patients who developed CMV retinitis were immunogenetically or immunologically predisposed. CMV retinitis develops in approximately 28-35% of AIDS patients and CMV encephalitis develops in 40% of those with retinitis, often leading to death. T-cell proliferation responses to CMV and HIV were assayed prospectively in individuals enrolled in a longitudinal study at the HIV Neurobehavioral Research Center (HNRC) in San Diego. Seventy-three participants, at various stages of disease, have been HLA typed and followed, clinically and immunologically, for up to 5 years. Six HIV infected individuals who eventually developed CMV retinitis, and were assayed prospectively, had a history of low T cell proliferation to CMV antigens before they were profoundly immunosuppressed. All 10 individuals with CMV retinitis had at least one of three HLA alleles (or combinations): A2B44 (p = 0.02), B51(p = 0.02), or DR7 (p = 0.01) (collective p value = 0.007). Three of the 10 had two or more of these alleles. Of AIDS patients with CD4 counts below 100 and actively at risk for retinitis, 7/15 with A2B44,51, or DR7 have developed retinitis compared to 0/13 without these HLA alleles (relative risk = 23.8). All 4 patients with these alleles who have died, had retinitis. These results suggest that HIV infected individuals with HLA phenotypes A2B44, B51, and DR7 have low T-cell immune responses to CMV and are predisposed to CMV retinitis and encephalitis as immunodeficiency progresses. PMID- 7874402 TI - Approach to the dizzy patient. AB - As dizziness can be caused by so many different pathophysiological mechanisms, it is crucial to determine the type of dizziness before proceeding with the diagnostic evaluation. Vertigo, defined as an illusion of movement, is an important subtype of dizziness that indicates a lesion somewhere within the vestibular system. Probably the most useful feature for differentiating between peripheral and central causes of vertigo is the associated symptoms. Vertigo of peripheral origin is typically associated with auditory symptoms such as hearing loss and tinnitus, while vertigo of central origin is nearly always associated with neurological symptoms such as diplopia, weakness, numbness and ataxia. Each of the common causes of vertigo has a characteristic clinical profile that should suggest a likely diagnosis after the history and examination are complete. Probably the most important treatment breakthrough is the positional manoeuvre that reliably cures benign positional vertigo (see Chapter 6). The treatment strategy for an acute peripheral vestibular lesion has evolved over the past few years. Patients are encouraged to return to normal physical activity as rapidly as possible. Repeated head, eye and body movements (vestibular rehabilitation) help the brain to recalibrate the relationship between visual, proprioceptive and vestibular signals (Chapter 9). PMID- 7874403 TI - Pharmacology of the vestibular system. AB - This chapter summarizes and critically evaluates the current understanding of neurotransmitter receptors operating within the peripheral and central vestibular systems. The available data suggest that the vestibular hair cell-vestibular nerve afferent synapses are mediated predominantly by an EAA transmitter (probably glutamate), acting on kainate-AMPA receptors; the contribution of NMDA receptors is uncertain. ACh may mediate the brainstem efferent-hair cell synapses; the role of GABA in the periphery is unclear. A large number of in vitro studies support the hypothesis that an EAA (probably glutamate) mediates vestibular nerve input to the MVN, acting predominantly on kainate-AMPA receptors; again, the contribution of NMDA receptors is uncertain. Whether another neurotransmitter such as ACh mediates vestibular nerve input to the LVN remains in question. Purkinje cell inhibition of ipsilateral LVN neurones is mediated by GABA, acting on GABAA receptors. MVN neurones have both GABAA and GABAB receptors; however, the GABAA receptors on MVN type I neurones appear to mediate brain-stem commissural inhibition via ipsilateral type II neurones. Receptors for DA, NA, 5-HT, histamine and several peptides have been identified on MVN and LVN neurones; at present, the precise function of these receptors remains to be elucidated. The significance of these data for the clinical treatment of vestibular disorders is discussed. PMID- 7874404 TI - New tests of vestibular function. AB - Three new, simple, clinically applicable tests of vestibular function are described. The first is a test of the response of the lateral semicircular canals to high accelerations. The test can even be done at the bedside where it can reveal severe unilateral or bilateral loss of lateral canal function. The test can also be recorded in a laboratory where it might show a less severe deficit of lateral canal function. The second is a simple, laboratory test of utricular function which depends on a subject's ability to align a bar with the subjective visual vertical. Patients with acute unilateral peripheral vestibular lesions invariably set the bar toward the side of the lesion. The third is a laboratory test of saccular function relying on a click-evoked inhibitory vestibulo-collic reflex recorded in the ipsilateral sternomastoid muscle. It can be done with equipment used for auditory evoked potentials. PMID- 7874405 TI - Posturography: uses and limitations. AB - The field of posturography has been advanced by the development of computerized dynamic posturography, wherein a force platform has been combined with visual stimuli as a means of determining the relative importance of the various sensory inputs critical for balance, namely vision, somatosensation and vestibular sensation. When compared with other tests currently available for the assessment of vestibular function, computerized dynamic posturography is unique in that it assesses 'balance' rather than attempting to assess peripheral or central vestibular function more directly. This discussion focuses on the device manufactured by NeuroCom International, marketed under the trade name Equitest. The sensory organization portion of the test has been shown to be most useful in the assessment of patients with suspected vestibular disorders. This chapter reviews the current status of computerized dynamic posturography based on published material. The vestibular pattern on computerized dynamic posturography has been observed in patients with ongoing vestibulospinal deficits. Another pattern has been labelled 'surface dependence' or 'combined visual-vestibular deficit'. Data suggest that 2-3 weeks after loss of unilateral peripheral vestibular function, most patients lose their vestibular pattern. Thus, posturography can provide valuable information regarding the status of compensation for a peripheral vestibular deficit. Results from computerized dynamic posturography may disagree with those from other vestibular laboratory testing, which suggests that posturography tests a different aspect of vestibular function than that assessed by electronystagmography and rotational testing. Computerized dynamic posturography does not provide localizing or lateralizing information, nor any information regarding aetiology; it does provide functional information regarding how well an individual can use their balance and an indication of the importance of a patient's balance disturbance on their activities of daily living. Also, computerized dynamic posturography provides a functional measure that is helpful in predicting the benefit that patients may expect to receive from therapeutic intervention with physical therapy. PMID- 7874406 TI - MRI of the inner ear. AB - The recent advances in MRI of the temporal bone brought about by the availability of intravenous contrast agents sensitive to the disruption of blood-brain barrier have further expanded the role of MRI in the evaluation of patients with vestibulocochlear symptoms. Not only can MRI be used to diagnose vestibular schwannomas (and other intracanalicular and cerebellopontine angle lesions mimicking it) with a high degree of accuracy, but it can now identify a variety of inflammatory and neoplastic processes of the membranous labyrinth which, in the past, were only made presumptively and occasionally confirmed by surgery and pathology. This enhanced diagnostic capacity of diseases of the vestibular cochlear system may help in the future to improve the management of these patients. PMID- 7874407 TI - A cure for benign positional vertigo. AB - Benign positional vertigo is a common clinical entity encountered in any dizzy clinic. It is easily diagnosed on the basis of historical information and a positive Dix-Hallpike position test. The available evidence suggests that this condition is due to involvement of the posterior semicircular canal. The pathophysiology of this condition can be explained theoretically on the basis of free-floating particles within the endolymph of the posterior semicircular canal that move under the influence of gravity with certain provocative positional changes. Based on this theoretical model, a variety of particle-repositioning manoeuvres have been developed that attempt to relocate the loose particles from the posterior semicircular canal to the utricular sac. If the particles are kept in the utricular sac for a period of 48 h by maintaining the patient in an upright position, the clinical symptoms are relieved in a high proportion of patients. If the manoeuvre is unsuccessful on a first attempt, or if the benign positional vertigo recurs at a later date, the condition can usually be relieved by a second manoeuvre. Bilateral benign positional vertigo can be treated by performing a manoeuvre on one side followed by a manoeuvre on the other side at a later date. On occasion, posterior canal benign positional vertigo is converted to horizontal canal benign positional vertigo, but this subsides readily within the 48-h post-manoeuvre period. PMID- 7874408 TI - Immune-mediated inner ear disorders. AB - Immune-mediated inner ear disease is characterized by sensorineural hearing loss which is most often rapidly progressive and bilateral, may be accompanied by vestibular symptoms, and for which no cause can otherwise be identified. The problem may occur alone or in combination with other systemic autoimmune disorders. Recognition of this entity is important as a substantial number of such patients experience improvement in hearing following treatment with corticosteroids with or without other immunosuppressive agents. Immune response to inner ear antigens can be helpful in establishing the diagnosis. The lymphocyte transformation assay has been used in identifying such responses but is limited by sensitivity and inhibited by immunosuppression. Western blot identification of serum antibodies to a 68-kD antigen of the inner ear appears to be a promising means of identifying patients with immune-mediated inner ear disease. The antibody is present in the majority of patients with clinical features consistent with the disorder; it correlates with disease activity and is predictive of response to treatment. Nevertheless, response to corticosteroid therapy remains the most convincing evidence of the disease. PMID- 7874409 TI - VIIIth nerve vascular compression syndrome: vestibular paroxysmia. AB - Neurovascular cross-compression of the root entry zone of the Vth, VIIth and IXth cranial nerves causes symptoms of trigeminal neuralgia, hemifacial spasm and glossopharyngeal neuralgia. It is reasonable to search for a group of patients presenting with typical paroxysmal vestibular and/or cochlear symptoms, analogously caused by neurovascular compression of the VIIIth cranial nerve. Since no pathognomonic sign or test has yet been established, the diagnosis of 'vestibular paroxysmia' secondary to neurovascular cross-compression is based on four characteristic features: (1) short attacks of rotational to-and-fro vertigo lasting seconds to minutes; (2) attacks frequently dependent on particular head positions and modification of the duration of the attack by changing head position ('disabling positional vertigo'); (3) hyperacusis or tinnitus permanently or during the attack; and (4) measurable auditory or vestibular deficits by neurophysiological methods. Carbamazepine is a most effective drug. In medically intractable cases, retromastoid craniotomy and microvascular decompression is a recommended procedure once the side of disorder has been identified. PMID- 7874410 TI - Vestibular rehabilitation. AB - Vestibular rehabilitation is a physical therapy programme for persons with symptomatic lesions of the vestibular system. When applied early in the course of recovery, it can hasten compensation. It can also reduce symptoms resulting from permanent deficits caused by vestibular injury. It has been shown to be effective when applied to patients with unilateral or bilateral losses, and reduces both dizziness and imbalance. Compensation occurs through tonic re-balancing at the level of the vestibular nuclei; by substitution of vision, proprioception and peripheral sensation for the missing vestibular input; and by the use of behavioural strategies to deal with residual deficits. The latter two mechanisms can be facilitated with rehabilitation exercises. Treatment methods must be varied, based on the patient's underlying disorder. The best prognosis for full recovery is for individuals with acute, unilateral vestibular injury. Patients with bilateral lesions will show improvement, but will have permanent deficits. Persons with progressive vestibular disorders, those having central involvement and persons with visual or somatosensory impairments may require more prolonged courses of treatment or demonstrate incomplete recovery. Patients with a previous history of vestibular loss with recent decompensation require a thorough re evaluation to rule out these more complex problems. Rehabilitation includes vestibular exercises, management of vestibular suppressant medications, general conditioning and patient instruction. Exercises should be directed at static and active posture and balance, eye-head co-ordination and symptomatic dizziness. Balance exercises include practice with standing, walking and turning. Eye-head co-ordination exercises require head movement during visual fixation or visual target changes. Treatment of symptomatic dizziness is based upon habituation to the provoking stimulus, usually head or eye movement. Home exercises are combined with formal physical therapy sessions and patient education to complete the process of rehabilitation. PMID- 7874411 TI - Invited review: tangential breast irradiation--rationale and methods for improving dosimetry. AB - In recent years there have been great advances and innovations in all technical aspects of radiotherapy, including three dimensional (3D) computer planning, patient immobilization, radiation delivery and treatment verification. Despite this progress, the technique of tangential breast irradiation has changed little over this period and has not exploited these advances. There is increasing evidence that dose inhomogeneity within the breast is greater than at other anatomical sites, especially in women with large breasts. This paper is a review of the factors contributing to poor dosimetry in the breast, the clinical consequences of an inhomogeneous dose distribution, and how breast dosimetry could be improved by considering each of the stages from planning to accurate treatment delivery. It also highlights the particular problem of women with large breasts who may be more likely to have a poorer cosmetic outcome after a fractionated course of radiotherapy than women with small/medium-sized breasts, and supports the clinical impression that such women are also more likely to have greater dose inhomogeneity when 3D treatment plans are examined. Preliminary data from our current computed tomography (CT) planning study are presented to support these observations. PMID- 7874412 TI - The relationship of pulmonary interstitial emphysema to subsequent type of chronic lung disease. AB - Chronic lung disease of prematurity (CLD) can be classified using the chest radiograph taken on day 28 into type 1 (homogeneous opacification) or type 2 (the presence of cystic change) and it has been suggested that the presence of pulmonary interstitial emphysema (PIE) leads to the development of type 2 CLD. To further study this relationship we examined the chest radiographs taken on days 1 7, 14, 21 and 28, of 202 infants treated at Liverpool Maternity Hospital between January 1980 and December 1989 who developed CLD. 39% (54/137) of infants who developed type 1 CLD had suffered from PIE compared with 78% (51/65) with type 2 CLD (p < 0.001). There was no difference in the incidence of PIE in infants who developed CLD and subsequently died compared with those who survived. In the infants who survived there was no significant difference in length of oxygen dependency between those who suffered from PIE (median 99 days oxygen dependent) and those who had no PIE (median 105 days). We conclude that the presence of PIE is associated with subsequent development of type 2 CLD but is not a prerequisite for this radiographic type of chronic lung disease. Of those infants who survive to develop CLD, the presence of PIE does not alter prognosis in terms of duration of oxygen dependency or mortality. PMID- 7874413 TI - Dynamic contrast-enhanced and fat suppressed magnetic resonance imaging in suspected recurrent carcinoma of the breast: preliminary experience. AB - 20 women with suspected recurrent breast cancer who had undergone previous breast conserving operations were investigated using dynamic contrast-enhanced gradient echo (GRE) and fat suppressed spin echo (SE) magnetic resonance (MR) imaging. Histologically confirmed recurrent tumour was readily recognized on dynamic GRE scans by virtue of rapid, early and avid enhancement. Benign scars enhanced more slowly and reached lower magnitudes of enhancement. Fat suppressed SE images, which were typically acquired 10 min after contrast administration, were sensitive for the detection of tumour recurrence but lacked specificity. Early scanning after contrast administration offers the best prospects for distinguishing tumour recurrence from benign scarring. The criteria used to distinguish these two entities are highly dependent on the scan technique and the time at which images are obtained post-contrast. PMID- 7874414 TI - Magnetic resonance neurography of the median nerve. AB - A magnetic resonance imaging sequence, combining fat and flow suppression with T2 weighting, has been used to produce high conspicuity images of the median nerve within the carpal tunnel. Standard maximum intensity projection techniques were then used to produce three-dimensional (3D) reconstructions of the nerve. Comparison of 3D projections with the wrist in a neutral position and wrist flexed at 45 degrees depicted changes in the shape and course of the median nerve through the carpal tunnel of normal volunteers. In some cases of carpal tunnel syndrome evidence of a localized compression was observed. A 3D image of a nerve may help in the diagnosis of peripheral neuropathy and be an aid to surgery of or near major nerves. PMID- 7874415 TI - Computed tomography of suspected lumbar disc protrusion in a district general hospital: outcome of scanning at L3/4. AB - 115 patients referred for computed tomography of suspected lumbar disc protrusion were surveyed retrospectively. In 42% of patients, signs and symptoms were clearly confined to the L5 or S1 root; in these cases, an abnormality at L3/4 on computed tomography did not result in surgery at L3/4. PMID- 7874416 TI - Pulled elbow in childhood. AB - In this injury, a sudden pull on the pronated, extended arm of a child up to 5 years of age is followed by refusal to use the arm. After a simple flexion, supination and extension manoeuvre the child starts using the arm in minutes. Radiographs are said to be normal. At least 13 theories of the mechanism have been advanced. Anterior subluxation of the radial head has never been proved radiographically or experimentally. Available evidence favours momentary distraction of the radiocapitellar joint in pronation which allows upward slip of the annular ligament upon the radial head at its shortest diameter and interposition of part of the anterior capsule between the two bones. Radiography is difficult, usually producing oblique views in pronation which are not easy to interpret. The main differential diagnosis is from epiphyseal rotation. In any doubtful case early repeat radiography is essential taking matched views of both elbows, even if non-standard. A collection of 28 radiographs has been analysed, two recent typical contrasting cases are presented, two signs to identify an oblique view of a normal elbow are described and the literature is reviewed. If the best radiograph available in an injured elbow in a child is a normal oblique view in pronation, pulled elbow is a likely diagnosis. PMID- 7874417 TI - Reconstruction of images from radiofrequency electron paramagnetic resonance spectra. AB - This paper discusses methods for obtaining image reconstructions from electron paramagnetic resonance (EPR) spectra which constitute object projections. An automatic baselining technique is described which treats each spectrum consistently; rotating the non-horizontal baselines which are caused by stray magnetic effects onto the horizontal axis. The convolved backprojection method is described for both two- and three-dimensional reconstruction and the effect of cut-off frequency on the reconstruction is illustrated. A slower, indirect, iterative method, which does a non-linear fit to the projection data, is shown to give a far smoother reconstructed image when the method of maximum entropy is used to determine the value of the final residual sum of squares. Although this requires more computing time than the convolved backprojection method, it is more flexible and overcomes the problem of numerical instability encountered in deconvolution. Images from phantom samples in vitro are discussed. The spectral data for these have been accumulated quickly and have a low signal-to-noise ratio. The results show that as few as 16 spectra can still be processed to give an image. Artifacts in the image due to a small number of projections using the convolved backprojection reconstruction method can be removed by applying a threshold, i.e. only plotting contours higher than a given value. These artifacts are not present in an image which has been reconstructed by the maximum entropy technique. At present these techniques are being applied directly to in vivo studies. PMID- 7874418 TI - Reduction of patient doses from barium meal and barium enema examinations through changes in equipment factors. AB - A study of patient doses for barium meal and barium enema examinations has been made for X-ray departments throughout Grampian Region. Dose-area products are substantially less than UK reference levels. Contributions from fluoroscopy and radiography varied significantly between different units, with fluoroscopy making up 35-92% of the mean doses for barium meals and 24-57% for barium enemas. Equipment related factors had a greater influence on patient doses than radiologists' techniques. The gain of the image intensifier and the exposure factors selected by the automatic exposure control (AEC) were the most important factors determining doses for fluoroscopy. Changes in kV/mA factors selected by the AEC have allowed reductions of 20-50% to be made in effective dose from fluoroscopy with some units. The method used for recording images was the major influence on radiographic doses. Digital spot images or fluorographic films taken from the intensifier gave only 10-20% of the dose with a film/screen system and are recommended where the image quality is satisfactory for the application. Changes in film/screen systems have given worthwhile reductions in radiographic doses. If all factors are optimized, mean doses for barium examinations could be reduced to 20% of current reference levels. PMID- 7874419 TI - Should broadband ultrasonic attenuation be normalized for the width of the calcaneus? AB - Broadband ultrasonic attenuation (BUA) is a measure of ultrasound transmission through the calcaneus that is dependent on bone thickness as well as the density of scattering centres. This report examines whether the normalization of BUA (units dB MHz-1) for calcaneal width (nBUA: units dB MHz-1mm-1) improves the discrimination of clinical studies. BUA and calcaneal width were measured in 200 women using a contact ultrasound (CUBA-Research) system and nBUA evaluated by dividing BUA by bone width. 150 subjects were early post-menopausal and the remaining 50 were osteoporotic women with confirmed vertebral crush fracture. The ability of BUA and nBUA to differentiate between the two groups of subjects was compared using receiver operating characteristic (ROC) analysis. The areas (and standard errors) under the ROC curves were 0.878 (0.033) for BUA and 0.910 (0.028) for nBUA. The difference (and standard error) between the areas under the ROC curves was 0.033 (0.026) and was not statistically significant. PMID- 7874420 TI - Precision and accuracy of measurements of whole-body bone mineral: comparisons between Hologic, Lunar and Norland dual-energy X-ray absorptiometers. AB - Measurements of whole-body bone mineral made by Hologic, Lunar and Norland dual energy X-ray absorptiometers have been compared. It was found that in each case the results were changed by new software protocols introduced by the manufacturers during the course of the study. With a moderately anthropomorphic model, the later software corrected some anomalies of regional bone mineral content (BMC) observed earlier. There was some slight dependence of total BMC on thickness and fat proportion and up to 15% difference between instruments. Measurements on volunteers showed good precision, but there were differences between instruments made by different manufacturers. There were high correlations, but the slopes of regression lines suggested differences of calibration of up to 8%; the standard errors of the estimates were 110 to 190 g. with maximum deviations from regression of 17%. There were regional disparities in BMC, particularly in the trunk, which arise (in part at least) from the imposition of a higher bone threshold by Hologic. From the pattern of results it was concluded that different assumptions were made by the manufacturers, particularly concerning the fat distribution model, which preclude the interchangeability of results from different instruments. PMID- 7874421 TI - Calculation of radiation induced complication probabilities for brain, liver and kidney, and the use of a reliability model to estimate critical volume fractions. AB - Radiation induced normal tissue complication probability is calculated for three different organs: brain, liver and kidney. The model applied is a reliability model where the volume effect of the tissue is described by the structural parameter, k, which reflects the architecture of the functional subunits (p) and the irradiated volume fraction (n). For partial, homogeneous irradiation of the brain, a k-value close to unity was found, and the respective values for liver and kidney were 0.92 and 0.77. An extension of the reliability model to account for individual inactivation probability of the subunits allows calculation of complication probability for inhomogeneous dose distributions. For the brain, intercomparison of a three-field and a two-field technique demonstrated a small reduction in complication probability for the former at low total doses. At high total doses a minimum complication probability was achieved applying a three field technique, being three times less than that associated with the two-field technique. PMID- 7874422 TI - Results of a questionnaire regarding the practice of radiotherapy for carcinoma of the cervix in the UK. AB - A questionnaire was sent to 50 departments of clinical oncology in the UK in September 1991. The aim was to determine the range of external beam and brachytherapy techniques employed at that time in the radical treatment of carcinoma of the cervix. Replies were received from 35 centres. This paper summarizes the preliminary findings of the study. Low dose rate (LDR) brachytherapy techniques predominated (34/35 = 97%) but 41% of departments (13/32) had future plans for the use of high dose rate (HDR) equipment. For low bulk (Stage I-II) carcinoma of the cervix, there was no detectable association between the total brachytherapy dose prescribed and the brachytherapy dose rate. In bulky (Stage I-II) carcinoma of the cervix treated by initial open teletherapy (without shielding), there was a statistically significant reduction in the prescribed brachytherapy dose with increasing dose rate. There was considerable variation between centres in the measurement or estimation of normal tissue doses during brachytherapy. The range of techniques used and the variation in expected complication rates should be closely monitored via medical audit and a further follow-up questionnaire may reveal important changes. PMID- 7874423 TI - Non-uniform dwell times in line source high dose rate brachytherapy: physical and radiobiological considerations. AB - The ability to vary source dwell times in high dose rate (HDR) brachytherapy allows for the use of non-uniform dwell times along a line source. This may have advantages in the radical treatment of tumours depending on individual tumour geometry. This study investigates the potential improvements in local tumour control relative to adjacent normal tissue isoeffects when intratumour source dwell times are increased along the central portion of a line source (technique A) in radiotherapy schedules which include a relatively small component of HDR brachytherapy. Such a technique is predicted to increase the local control for tumours of diameters ranging between 2 cm and 4 cm by up to 11% compared with a technique in which there are uniform dwell times along the line source (technique B). There is no difference in the local control rates for the two techniques when used to treat smaller tumours. Normal tissue doses are also modified by the technique used. Technique A produces higher normal tissue doses at points perpendicular to the centre of the line source and lower doses at points nearer the ends of the line source if the prescription point is not in the central plane of the line source. Alternatively, if the dose is prescribed at a point in the central plane of the line source, the dose at all the normal tissue points are lower when technique A is used. PMID- 7874424 TI - Quantitative magnetic resonance for assessment of radiation fibrosis after post mastectomy radiotherapy. AB - Subcutaneous fibrosis is a serious complication of post-mastectomy radiotherapy with a pronounced influence on skin conditions, shoulder movement and arm oedema. To establish safer radiotherapy schedules, precise evaluation of the tissue damage is required. A feasibility study was performed to assess the value of calculated relaxation times from magnetic resonance (MR) images for quantitative characterization of different degrees of subcutaneous fibrosis after post mastectomy radiotherapy. A surface coil was applied to the irradiated area, as well as to unirradiated skin, to obtain appropriate MR coronal slices for acquisition of calculated values using a mixed imaging sequence technique. 14 patients with clinically diagnosed subcutaneous fibrosis were examined, 10 of whom had severe fibrosis. The mean T2 values of the treated and untreated side were 53.0 and 56.7, respectively. A statistically significant decrease of the calculated T2 values on the treated side was observed. No correlation was found between the clinically assessed fibrosis and the calculated relaxation times. The findings indicate that despite a general decrease of T2 calculated values, the large variation in the relaxation times restricts the value of MR, as applied in this study, in differentiating between different degrees of fibrosis in normal tissues after radiotherapy. PMID- 7874425 TI - Technical note: a moderately sized resonator/surface coil for radiofrequency electron paramagnetic resonance spectroscopy and imaging in vivo. AB - A resonator for the radiofrequency (250 MHz) electron paramagnetic resonance spectroscopy (EPRS) and imaging (EPRI) of biological samples is described. It has been designed for use with a 0.5 m bore EPR spectrometer. It is of the double split-ring type, 65 mm in diameter and 100 mm in length, and is equipped with a tuning-lock mechanism for fixed frequency operation. It can be used in the whole body mode for small animals and as a surface coil for larger samples. The extent of sensitivity in the latter mode is ca. 20 mm. Larger resonators are being developed for whole-body human studies. A phase-locked crystal oscillator frequency source with high spectral purity is used to minimize noise demodulation and automatic tuning; coupling and phase controls have been included to compensate for motional artefacts. For purely aqueous nitroxides, the minimum detectable concentration is ca. 4 x 10(-7) M using an internal sample 100 ml in volume. Sensitivity in the surface coil mode is discussed and spectra from phantoms using both physiological saline and a human volunteer to induce realistic conduction losses are shown. PMID- 7874426 TI - Technical note: reducing motion artifacts in in vivo magnetic resonance imaging measurements of relaxation times. AB - Robust and accurate methods of measuring relaxation times on commercial scanners have recently been developed. Such methods overcome many machine and sequence dependent errors, but are still subject to errors arising from motion artifacts. This paper considers methods of decreasing the effect of motion artifacts in in vivo T1 and T2 measurements. Three conventional techniques for reducing such artifacts are assessed for their use with relaxation time measurement sequences. It is shown that these techniques do not adversely affect the accuracy of phantom T1 measurements made with the spin echo/inversion recovery sequence, and of T2 measurements made using the PHAPS sequence. For in vivo measurements of T1 it is also shown that these techniques reduce the standard deviation of T1 measurements in regions of interest and improve the reproducibility of such measurements overall. Two other techniques for reducing motion artifacts were found not to be compatible with the accurate measurement of relaxation times. PMID- 7874427 TI - Technical note: use of a double inversion recovery pulse sequence to image selectively grey or white brain matter. AB - The design of a double inversion recovery (DIR) sequence, to image selectively grey or white brain matter, is described. Suitable choice of inversion times allows either cerebrospinal fluid (CSF) and white matter to be suppressed, to image the cortex alone, or CSF and grey matter to be suppressed, to image the white matter. The DIR sequence was found to give clear delineation of the cerebral cortex. PMID- 7874428 TI - Case report: traumatic aortic rupture: demonstration by magnetic resonance imaging. AB - Traumatic rupture of the aorta is a major cause of morbidity and mortality in rapid deceleration road traffic accidents, with an immediate mortality of 85%. Of the 15% that survive the initial injury, approximately 50% will die within 24 h if left untreated. Prompt diagnosis and early surgical treatment are necessary if such patients are to survive. Aortography is the standard investigation of choice and provides a rapid, sensitive test of aortic rupture. Other modalities, such as plain chest radiography, computed tomography (CT) and ultrasound may also play a role in diagnosis. Magnetic resonance imaging (MRI), with its multi-planar imaging capability, is now widely used for imaging non-traumatic disorders of the aorta. However, its use in traumatic rupture has been limited by difficulties in monitoring and in access to the patient during the scan. We present a patient who survived the initial injury, when the diagnosis of aortic rupture was not suspected. and presented 3 weeks later with chest pain. An MRI scan was feasible as the patient was haemodynamically stable, and it provided an elegant non invasive means of diagnosis, so that aortography was not necessary in this case. Although aortography is likely to remain the investigation of choice in the acute situation, MRI is a useful alternative in selected cases. PMID- 7874429 TI - Case report: asymmetrical development of the gyri recti presenting as a suprasellar mass: case report and description of six further cases. AB - Asymmetrical appearances of normal anatomical structures can sometimes mimic pathology. We present a case where asymmetry of the gyri recti was interpreted as a suprasellar mass on axial CT scanning. The true nature of the apparent abnormality was revealed by coronal magnetic resonance imaging (MRI). We also present six further cases where asymmetrical gyri recti were noted as incidental findings on coronal MRI scans. This is a common, but important, normal anatomical variant, which should not be mistaken for pathology. PMID- 7874430 TI - Case report: bowel infarction with splenic air embolism: computed tomography findings. AB - Computed tomography (CT) is used increasingly as an early radiological examination in patients with suspected bowel infarction because it provides information about the intestinal wall, mesenteric circulation and peritoneal cavity [1, 2]. Other disorders that present with similar symptoms such as intraabdominal abscess, pancreatitis and ulcerative colitis can be excluded [3]. CT can demonstrate small amounts of air within the bowel wall, in the spleno mesenteric-portal venous system and in the peritoneal cavity, making it possible to differentiate portal venous gas from pneumobilia. The authors describe a patient in whom a specific diagnosis of bowel infarction was made on the characteristic CT findings. Furthermore, air embolism was observed in the splenic parenchyma. This finding has not been previously reported in bowel infarction or in any other abdominal disorder. PMID- 7874431 TI - Case report: the "aurora sign"--a new sonographic sign of pneumatosis cystoides intestinalis. AB - Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by multiple gas-filled cysts of varying size within the intestinal wall. Although the characteristic findings on plain abdominal radiograph, computed tomography (CT), and barium enema have been well described, the sonographic findings have not. We recently encountered a case of PCI in which abdominal sonography disclosed a unique finding. We were able to reproduce the finding experimentally and have coined it the "aurora sign". PMID- 7874432 TI - Case of the month: a lump in the throat. PMID- 7874433 TI - The siting of consistency checks on mobile image intensifier automatic brightness controls. PMID- 7874434 TI - Identification of interactive determinants on idiotypic-anti-idiotypic antibodies through comparison of their hydropathic profiles. AB - We have written a computer program to aid in the identification of interaction sites between proteins. The program compares the hydropathic profiles of the two interacting proteins and reports sites, demonstrating an exact pattern of inverted hydropathy. If these regions are surface accessible in the folded proteins, they are considered putative binding or docking sites and can be tested as such. In this report, we apply this program to the localization of residues involved in the anti-idiotope of a monoclonal antibody (mAb), F30C7. The anti idiotope of F30C7 partially resembles the structure of the peptide antigen, human myelin basic protein (MBP) acetyl 1-9, used to elicit the idiotope bearing mAbs (Ab1). The sequences of F30C7 variable regions are compared to the variable regions of Ab1, as well as to the peptide antigen used to elicit F30C7. Sites of hydropathic complementarity in F30C7 with Ab1 that also have sequential homology with MBP 1-9 were located, and a synthetic peptide designed from these sequences was found to structurally resemble MBP 1-9 in that it: (i) inhibited Ab1 binding to MBP 1-9 and (ii) partially inhibited the binding of F30C7 to Ab1. Thus the portion of the anti-idiotope of F30C7 resembling MBP 1-9 was determined with the aid of this program. Other hits between F30C7 and Ab1 also occurred, and future studies will determine whether or not these sites might further contribute to the anti-idiotope. PMID- 7874435 TI - Identification of interactive sites of proteins and protein receptors by computer assisted searches for complementary peptide sequences. AB - Protein sites important for receptor binding have been identified in several systems by searching for protein/receptor stretches characterized by hydropathic anti-complementarity. A computer-assisted method [SITESEARCH] has been developed to identify protein sites responsible for receptor recognition, once the amino acid sequences of the protein ligand and its receptor are available. The software first determines the hydropathic profiles of the two polypeptide chains under investigation, and then compares profiles of preselected length, determining at the same time the degree of their hydropathic complementarity. The procedure is repeated until all the different segments in the two chains are compared. Fragments characterized by the maximal level of hydropathic complementarity are selected as putative binding sites. This approach has been initially applied to the interleukin-1 beta (IL-1 beta)/receptor type I case. SITESEARCH identified residues 88-99 in IL-1 beta and 151-162 in the receptor as the sequence pair characterized by the maximal level of hydropathic complementarity. These fragments, once produced by chemical synthesis, have displayed specific recognition properties for each other, as detected by solid-phase binding assays. The IL-1 beta sequence identified corresponds to a highly exposed part of the protein molecule, and substitution of this sequence with another of the same length but with different hydropathic characteristics generated mutants with drastically reduced binding activity to the receptor. Mutations in this sequence did not alter the protein biological activity, thus suggesting the structural integrity of the mutants. Cumulatively, these results validate the SITESEARCH prediction, suggesting that IL-1 beta sequence 88-99 is involved in at least a portion of the protein/receptor binding site. PMID- 7874436 TI - Complementary peptides as antibody mimetics for protein purification and assay. AB - The possibility of designing sequence-directed recognition peptides (complementary peptides) able to noncovalently associate target peptides or proteins is one of the most important biotechnological applications deriving from the molecular recognition theory [MRT]. Complementary peptides can be used widely as synthetic ligands for the development of affinity purification strategies to isolate target peptides or proteins from crude sources. Generally, the observed affinity and selectivity are sufficient to allow one-step purification of target molecules directly from crude mixtures and the possibility of producing the ligands in enzymatically stable forms greatly enhance their applicability. In addition, the noninterference of nonionic detergents or denaturants on recognition expand their use in the case of poorly soluble targets. The ligand's synthetic nature overcomes all the problems associated with the use of immunoaffinity columns, since the possibility of biological contaminations is extremely limited. Numerous examples demonstrate the usefulness of this methodology, which allows the creation of a large number of peptidyl ligands tailored to specific purification needs. Recognition properties of complementary peptides can be applied also to the development of solid-phase assays for the identification and quantification of different molecular targets. As antibody mimetics, they can be used on solid phases to capture, and then to detect and consequently quantify, the desired target polypeptide in complex biological mixtures. Even if assay sensitivity cannot be compared with conventional antibody based assays, the simplicity of complementary peptide design and production makes their use an attractive alternative in various circumstances. PMID- 7874437 TI - Use of complementary peptides and their antibodies in B-cell-mediated autoimmune disease: prevention of experimental autoimmune myasthenia gravis with a peptide vaccine. AB - We have developed and describe a new method of altering B-cell-mediated autoimmune diseases by induction of anti-idiotypic (Id) antibodies (Abs) by immunization with complementary peptides. Specifically, a peptide denoted RhCA 67 16 encoded by RNA complementary to RNA for the Torpedo acetylcholine receptor (AChR) main immunogenic region, AChR 61-76, was tested in the Lewis rat model of experimental autoimmune myasthenia gravis (EAMG). Immunization with RhCA 67-16 induced monoclonal and polyclonal anti-Id Ab against Abs to Torpedo AChR 61-76. RhCA 67-16 antisera inhibited AChR binding by AChR-specific Abs. In addition, a mAb to RhCA 67-16 (denoted TCM 240) recognized two well known EAMG-causing mAbs, 6 and 35. TCM 240, but not a control mAb F28C, inhibited mAb 6 binding to Torpedo AChR 67-76 peptide. mAb 35 binding to TCM 240 was inhibited by native Torpedo AChR as well as by RhCA 67-16. In in vivo experiments, immunization with a RhCA 67-16 keyhole limpet hemacyanin (KLH) conjugate blocked the development of EAMG after challenge with native Torpedo AChR (25% disease incidence versus 90% in the controls). This new approach may provide a novel therapy for MG and perhaps other B-cell-mediated autoimmune disorders through the induction of anti-Id Abs with complementary peptide antigens. PMID- 7874438 TI - Complementary peptides that interfere with platelet aggregation and adherence. AB - This article describes the application of the molecular recognition hypothesis to the critically important process of fibrinogen binding to platelets, a process that is the subject of extensive and intensive basic and clinical research. The objectives of the studies summarized below were to design, synthesize, and characterize peptides that can inhibit the binding of fibrinogen and related ligands to human platelets and thereby prevent platelet aggregation, adhesion, and clot retraction. The purpose of doing this work was twofold: first, to determine whether the molecular recognition hypothesis could serve as a useful rationale for the design of peptides that can specifically inhibit the binding of fibrinogen and related ligands to platelets; and second, to use these peptides to try to learn where fibrinogen binds to the platelet fibrinogen receptor. It was hoped that the results obtained not only would provide insight into platelet function but also might provide a rationale for the design of a clinically useful anti-thrombotic agent. Although our studies are not complete, they have resulted in the design of a variety of peptides that can inhibit platelet aggregation, adhesion, and clot retraction as a consequence of specifically inhibiting the binding of fibrinogen and related ligands to the platelet fibrinogen receptor. Although none of these peptides appears to be ligand specific, one or two of them may be specific for platelets. PMID- 7874439 TI - Antibodies to complementary peptides as probes for receptors. AB - Peptide hormones initiate their physiological responses by binding to receptor proteins embedded in the plasma membranes of their target cells. Mechanisms accounting for specific protein-protein interactions, such as peptide hormone binding by cell receptors or epitope binding by antibody have not been defined. A fundamental tenet of the immunological network hypothesis is the generation of anti-idiotypic antibodies to epitopes located in the hypervariable regions of antibody evoked in the same animal species. Anti-idiotypic antibodies to antibodies to peptide hormones with specificity for epitopes involving antibody binding sites may mimic the actions of the peptide hormone by binding to receptors and evoke cell responses associated with the hormone. A provocative relationship was identified in the genetic code, which recognized that complementary codons for strongly hydrophobic amino acids code for strongly hydrophilic amino acids. This led to the proposal and then to demonstration that peptide pairs based on the nucleotide sequences of complementary codons bind one another. It was then proposed that immunization with complementary peptides to peptide hormones may produce antibodies which, analogous to anti-idiotypic antibodies, may mimic the hormone. Some antibodies to complementary peptides for peptide hormones have been shown to mimic the peptide hormones by binding to their receptors and evoking cell responses characteristic of those of the hormones. Exploiting these relationships, some antibodies to complementary peptides for peptide hormones have been used to identify, purify, and characterize receptor proteins for peptide hormones. Polypeptide hormones initiate their characteristic physiologic effects by binding to specific receptor proteins located on the plasma membranes of their target cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874440 TI - Complementary peptides as probes to explore neuropeptide receptors on lymphocytes. AB - Studies on neuroendocrine hormone receptor have been hampered by low numbers and concentrations of receptors found within and outside the neuroendocrine system. The complementary peptide approach is particularly useful for dealing with this problem and has been used to characterize lymphoid receptors for arginine vasopressin (AVP), corticotropin (ACTH), substance P, and opioid peptides. A nonapeptide derived by reading of the complementary DNA strand of the bovine AVP gene in the 3' to 5' direction specifically blocks the AVP helper signal for interferon-gamma production by mouse T lymphocytes. Antibodies to 3'-5' AVP binding peptide bound to cells, and the binding was inhibited by excess AVP. Thus, binding of anti-3'-5'AVP-binding peptide antibodies to the AVP receptor was specific. The complementary peptide approach has also been used to produce antibodies specific for the ACTH receptor complex. Complementary peptides to ACTH derived by reading in either the 5' to 3' or 3' to 5' direction were able to bind to ACTH. Monospecific antibodies to the ACTH (1-24) complementary peptide caused an ACTH-like steroidogenic response of cultured mouse adrenal cells, presumably by binding to the ACTH receptor, and binding was specifically inhibited by ACTH. The ACTH receptor complex from solubilized adrenal cells was shown to consist of four subunits with M(r) 83,000, 64,000, 52,000, and 22,000. The 83,000 and 52,000 M(r) subunits are disulfide linked and noncovalently associated with the other subunits, with binding of labeled ACTH localized to the 83,000 M(r) subunit. Similarly, a complementary peptide was shown to bind directly to substance P in a saturable and dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874441 TI - A monoclonal autoantibody against a complementary peptide recognizes interstitial collagenase. AB - A monoclonal autoantibody (mab 16) against the complementary peptide TKKTLRT, which was deduced from the collagenase-sensitive site in collagen, is described. Mab 16 recognized interstitial collagenase as visualized by ELISA and immunoprecipitation assays. Moreover, mab 16 was able to inhibit partially the collagenolytic activity of keratinocyte supernantant. Finally, it was possible to immunopurify collagenase using a mab 16/Sepharose column. PMID- 7874442 TI - Peptide design using a genetically patterned binary code: growth hormone releasing hormone as a model. AB - This paper reviews a method for the design of peptides and proteins of predefined structure and function and provides an example. Specifically, an analog of rat growth hormone-releasing hormone (GHRH) (residues 1-23) was synthesized by solid phase methods based on a reversed sequence of the mRNA for GHRH (1-23). The new peptide, designated GHRH 3'-5', had a hydropathic profile similar to that of native GHRH 5'-3' (GHRH) but had only 17% primary sequence homology. GHRH 3'-5' specifically bound to the GHRH receptor on rat pituitary cells and to polyclonal anti-GHRH antibody in ELISA and RIA procedures. Additionally, GHRH 3'-5' blocked the in vitro stimulation of GH RNA synthesis and in vitro and in vivo GH release mediated by GHRH. These data show that 3'-5' GHRH with little sequence homology to native rat GHRH is an antagonist and further supports the importance of the linear pattern of hydropathy to the gross secondary and/or tertiary structure and rudimentary function of peptides and proteins. The impact of these findings on the interaction of complementary peptides is discussed. PMID- 7874443 TI - Nuclear magnetic resonance studies on complementary peptides. AB - From the original observation that the codons for the hydrophobic and hydrophilic amino acids on one strand of the DNA may be complemented by the codons for the hydrophilic and hydrophobic amino acids, respectively, on the complementary strand, arose the molecular recognition theory which forms the basis for much of the work involving complementary peptides. A number of examples have been documented where peptides with inverted hydropathic profiles have been shown to form complexes in high-affinity chromatography and solid matrix binding assays. Nevertheless, our current understanding of the molecular forces leading to the formation of these complexes is rather rudimentary, and it is highly desirable to have a detailed three-dimensional structure of a complex of interacting complementary peptides. In this article, we provide a brief review of the solution NMR work done by different laboratories in an attempt to study these interactions. PMID- 7874444 TI - Signal transduction by granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors. AB - Granulocyte-macrophage colony stimulating factor (GM-CSF) and Interleukin-3 (IL 3) are cytokines which stimulate myeloid bone marrow progenitor cell proliferation and maturation. GM-CSF also enhances the function of terminally differentiated effector cells including neutrophils, monocytes and eosinophils. Both growth factors exhibit similar biological activities on overlapping cell populations which are mediated by high affinity receptors. These receptors share a common beta subunit necessary for signal transduction. The receptors for GM-CSF and IL-3 are members of the hematopoietin receptor superfamily and consequently lack intrinsic tyrosine kinase activity. Several kinases, including JAK2 and raf 1, and other downstream molecules are likely to be responsible for the functional redundancy demonstrated by GM-CSF and IL-3 in factor-responsive cells. This review discusses recent findings which elucidate the signaling pathways activated by these two cytokines. PMID- 7874445 TI - Cloning and expression of a family of inward rectifier potassium channels. AB - Five new members of the two-transmembrane domain potassium channel family have been identified from rat brain, heart and skeletal muscle. The channel mRNAs are differentially expressed and found in both the central nervous system and periphery. Expression of two of these channels in Xenopus oocytes gave rise to inwardly rectifying potassium currents which were voltage-dependently blocked by barium and cesium. Voltage command pulses negative to Ek evoked inward currents which rapidly reached a peak amplitude and relaxed to a steady-state level. The quantity of current relaxation differed in the two channels and was increased at more negative potentials. The degree of current rectification was also different for the two channels. The results demonstrate the existence of a large and widely expressed family of inward rectifier potassium channel subunits with distinct tissue distributions and functional properties. PMID- 7874446 TI - Shab gene expression in identified neurons of the pyloric network in the lobster stomatogastric ganglion. AB - A single shab gene exists in the lobster, Panulirus interruptus, and undergoes alternate splicing to produce multiple transcripts. Using in situ hybridization we have determined the expression pattern of the shab gene in identified neurons of the pyloric network. The shab gene is consistently expressed at a low level in the Ventricular Dilator cell, a high level in the Pyloric Dilator cell, and is not detectably expressed in the Lateral Pyloric or Inferior Cardiac cells. Shab gene expression in the Anterior Burster cell varies from animal to animal. The electrophysiologically heterogeneous group of eight Pyloric Constrictor cells also shows differences in shab gene expression. These results support the idea that differences in shab gene expression contribute to the unique electrophysiological phenotypes displayed by each cell type. PMID- 7874447 TI - Cloning of the human homologue of the GABA transporter GAT-3 and identification of a novel inhibitor with selectivity for this site. AB - Molecular cloning has revealed the presence of four high-affinity GABA transporters in the brain. The existence of three of these sites, GAT-2, GAT-3, and BGT-1, was unknown prior to their cloning and almost nothing is known of the role they play in regulating GABAergic transmission. In large measure our paucity of knowledge is attributable to the lack of specific inhibitors for these sites. In the present communication we describe the cloning and expression of the human homologue of GAT-3, and the identification of an inhibitor, (S)-SNAP-5114, with selectivity for this site. (S)-SNAP-5114 displays an IC50 of 5 microM at GAT-3, 21 microM at GAT-2, and > or = 100 microM at GAT-1 and BGT-1. Due to its lipophilicity, (S)-SNAP-5114 is also expected to cross the blood-brain-barrier and therefore, should be an important tool for evaluating the role of GAT-3 in neural function. PMID- 7874448 TI - Cardiac calcium channels expressed in Xenopus oocytes are modulated by dephosphorylation but not by cAMP-dependent phosphorylation. AB - Enhancement of cardiac L-type Ca2+ channel activity by norepinephrine via phosphorylation by protein kinase A (PKA) underlines the positive inotropic effect of this transmitter and is a classical example of an ion channel modulation. However, it is not clear whether the channel protein itself (and which subunit) is a substrate for PKA. We have expressed various combinations of the cardiac Ca2+ channel subunits in Xenopus oocytes by injecting subunit mR-NAs. Expression of beta or alpha 2/delta + beta subunits potentiated the native (endogenous) Ca2+ channel currents in the oocyte (similar to T or N but not L type). This potentiated endogenous current was enhanced by intracellular injection of cAMP or of the catalytic subunit of PKA, and this effect was reversed by the injection of a PKA inhibitor suggesting the presence of basal phosphatase activity. When a cardiac channel of alpha 1 + beta, alpha 1 + alpha 2/delta or alpha 1 + alpha 2/delta + beta composition was expressed at levels high enough that the contribution of the endogenous current became negligible, cAMP and PKA failed to increase the Ca2+ channel current, whereas PKA inhibitors and the catalytic subunit of protein phosphatase 1 reduced the amplitude of the current. Reduction of the current by PKA inhibitors was observed regardless of the presence of the beta subunit, suggesting a major role for the alpha 1 subunit in this process. These results suggest that, like in the heart, when expressed in Xenopus oocytes, the cardiac L-type Ca2+ channels are phosphorylated in basal state and dephosphorylation reduces their activity. However, unlike the situation in the heart, the activity of the channel cannot be enhanced by PKA-catalyzed phosphorylation, suggesting that the channel is already fully phosphorylated in its basal state. PMID- 7874449 TI - Homomeric rho 1 GABA channels: activation properties and domains. AB - Expression of human rho 1 subunits in Xenopus laevis oocytes forms homomeric GABA activated chloride channels with activation and pharmacological properties distinct from those of typical heteromeric GABA channels (e.g., alpha 1 beta 2 gamma 2). Here, we describe these rho 1 activation features and use site-directed mutagenesis to identify amino acids involved in GABA-mediated activation. In comparison to heteromeric GABA channels (alpha 1 beta 2 gamma 2), GABA channels comprised of rho 1 subunits are approximately 40-fold more sensitive to GABA, activate 8.3-fold more slowly (at a GABA concentration equal to their respective EC50S), do not desensitize with maintained agonist application, and close approximately 8-fold more slowly after agonist removal. Site-directed mutagenesis of rho 1 GABA channels has identified five amino acids (Y198, Y200, Y241, T244, and Y247) located between the N-terminal extracellular cysteine loop and first membrane spanning domain, that when conservatively mutated, significantly impaired GABA-mediated activation. These five residues are grouped in two domains that correspond in position to the putative agonist-binding domains previously identified for the beta 2 subunit of alpha 1 beta 2 gamma 2 GABA channels. Y198, T244, and Y247 correspond directly to crucial amino acids identified in the beta 2 subunit; Y200 and Y241 do not. These differences may account, in part, for the unique activation and pharmacological features of homomeric rho 1 GABA channels. PMID- 7874450 TI - Role of an invariant cysteine in gating and ion permeation of the voltage sensitive K+ channel Kv2.1. AB - We examined the role of two invariant cysteines, one in S2 and one in S6, of the voltage-gated K+ channel Kv2.1 (DRK1) by site-directed mutagenesis and subsequent channel expression in Xenopus oocytes. Despite the conserved nature of the side chain, substitutions in S2 were generally tolerated. Fourteen of 17 substitutions for Cys 232 in S2 resulted in voltage-sensitive K(+)-selective channels, for the most part with minor changes in voltage dependence and channel kinetics. In contrast, only 7 of 19 substitutions for Cys 393 in S6 preserved channel function. Furthermore, the side chain at this position influenced deactivation kinetics, inactivation kinetics, and ion-permeation properties. The chemical nature but not the volume of the side chain governed the rate constants of deactivation and inactivation. In contrast, changes of the volume of the side chain but not of its chemical properties correlated with changes in ion conductance. Our results indicate that the side chain at position 393 in S6 is involved in conformational changes during transitions between open and closed states and that it also contributes to the control of ion permeation. PMID- 7874451 TI - Voltage-dependent Na+ channel mRNA expression in pregnant myometrium. AB - The mechanisms responsible for the onset of vigorous contractile activity in uterine muscle at the time of parturition, reversing the obligatory quiescence of pregnancy, remain poorly understood. We here describe the expression in myometrium from human and from timed-pregnant rats of an mRNA species encoding a voltage-sensitive sodium channel. The apparent concentration of this mRNA species, as measured by reverse-transcription polymerase chain reaction, underwent an approximately four-fold decline between mid-gestation and term. These results complement earlier reports of increased sodium current expression in mid- and late pregnancy and further support a role for smooth muscle sodium current in late pregnancy and/or labor. PMID- 7874452 TI - Cytochalasin B does not block sperm penetration into denuded starfish oocytes. AB - During fertilisation in starfish oocytes, the fertilisation cone develops temporarily beneath the penetrating sperm. The role of the fertilisation cone in sperm incorporation in the starfish Asterias amurensis was examined using cytochalasin B (CB). CB (2 microM) allowed sperm acrosomal process-egg plasma membrane fusion and egg activation, but inhibited the development of the fertilisation cone containing actin microfilaments. When sperm were added to intact oocytes (with the jelly coat and vitelline coat) in seawater containing CB, the sperm head did not penetrate the fertilisation membrane. Although the acrosomal process fused with egg plasma membrane, the sperm head remained outside the fertilisation membrane. On the other hand, denuded oocytes without the jelly coat and vitelline coat allowed sperm penetration even in the presence of 2 microM CB. Electron microscopy revealed that sperm organelles, including the acrosomal process, nucleus, mitochondrion and tail, were incorporated into the slightly electron-dense cytoplasm, which was similar to the cytoplasm of the fertilisation cone. These results show that the development of the fertilisation cone/actin filament complex is not essential for incorporation of the sperm, since incorporation can occur in denuded oocytes. However, the cone is required for fertilisation of intact oocytes, suggesting that this actin-filament containing structure is necessary for getting the sperm through the outer egg coats. PMID- 7874453 TI - Confocal microscopy of F-actin distribution in Xenopus oocytes. AB - We have used rhodamine-conjugated phalloidin and confocal microscopy to examine the organisation of filamentous actin (F-actin) during oogenesis in Xenopus laevis. F-actin was restricted to a thin shell in the cortex of oogonia and post mitotic oocytes less than 35 microns in diameter. In oocytes with diameters of 35 50 microns, F-actin was observed in three cellular domains: in the cortex, in the germinal vesicle (GV) and in a network of cytoplasmic cables. Initially, actin cables were sparsely distributed in the cytoplasm, with no evidence of discrete organising centres. In larger stage I oocytes, a dense network of actin cables extended throughout the cytoplasm, linking the GV and mitochondrial mass to the cortical actin shell. Apart from the F-actin associated with the mitochondrial mass, no evidence of a polarised distribution of F-actin was apparent in stage I oocytes. F-actin was observed also in the cortex and the GV of stage VI oocytes, and a network of cytoplasmic cables surrounded the GV. Cytoplasmic actin cables extended from the GV to the animal cortex, and formed a three-dimensional network surrounding clusters of yolk platelets in the vegetal cytoplasm. Finally, disruption of F-actin in stage VI oocytes with cytochalasin resulted in distortion and apparent rotation of the GV in the animal hemisphere, suggesting that actin plays a role in maintaining the polarised organisation of amphibian oocytes. PMID- 7874454 TI - In vitro fertilisation of maize by single egg and sperm cell protoplast fusion mediated by high calcium and high pH. AB - We present evidence for the fusion of isolated single maize egg and sperm cell protoplasts in a mannitol solution (400-430 mosmol/kg H2O) containing 0.05 M CaCl2 at pH 11.0, followed by cell division of the fusion products. These findings allow the performance of in vitro fertilisation of higher plants by combining single gametes as in lower plant and animal systems. Further, our findings open new avenues for investigating the basic mechanisms of adhesion and fusion of higher plant gametes and eventually for examining processes that inhibit polyspermy in higher plants. PMID- 7874455 TI - Sperm entry into fertilised mouse eggs. AB - We have investigated the oolemma block to polyspermy in the mouse. Zona-free and zona-intact eggs were fertilised and subsequently re-inseminated (the latter following zona pellucida removal). The 'perivitelline' block to polyspermy in zona-intact eggs renders motile sperm in the perivitelline space unable to bind to the oolemma. This is not connected with irreversible changes in the egg plasma membrane, because freshly added sperm can still fuse with such eggs freed from the zona. Fertilised eggs eventually lose the ability to fuse with sperm within 1 h, while still being able to bind many sperm. PMID- 7874456 TI - Human cumulus cell complexes studied in vitro by light microscopy and scanning electron microscopy. AB - Various researchers describe the morphology of cumulus cells (CC) in vitro, but few have investigated their behaviour on plastic. Knowledge concerning the behaviour of human CC could be useful in improving the success of in vitro fertilisation procedures. This study aimed to describe the morphology and behaviour of CC in vitro and to investigate movement on a collagen-coated substrate. Following collection some cumulus were mechanically dissected from those surrounding the oocyte. Cumulus aggregates were cultured over 24 h using Earle's medium supplemented with 8% albumin. Substrata were plastic coverslips coated with collagens I, IV, or mixed collagens. Cumulus cultured over corresponding time periods on uncoated coverslips served as controls. Specimens were fixed and prepared for scanning electron microscopy. Over 24 h the controls began exhibiting the morphological features associated with cell movement: cell surface protrusions changed from blebs to microridges, lamellipodia and leading lamellae; cell shape altered from rounded and upright, to flattened. Extracellular matrix (ECM) transformed from a thick, sheet-like substance to a thin, fibrous material. By 24 h, cells contacting ECM remained rounded showing few features of movement. Collagens enhanced attachment of CC as a monolayer on the substrate. Cell morphology varied according to the collagen type used. On mixed collagens, cells attached rapidly, appearing to be predominantly non motile. On collagen type I there was less attachment of cells but increased motility. On collagen type IV there was decreased attachment and the cells remained spherical. In conclusion, collagens enhance the settling of cumulus cells on a plastic substrate and the cells exhibit some specificity in attaching to collagens. PMID- 7874457 TI - Sperm-egg fusion in the sea urchin is blocked in Mg(2+)-free seawater. AB - Magnesium ions as well as calcium ions are required for successful fertilisation in sea urchins. In the absence of Mg2+ spermatozoa attached to the egg plasma membrane, their acrosomal processes passing through the vitelline envelope, but could not enter the egg cytoplasm (Sano et al., Dev. Growth Differ. 22, 531-41, 1980). Such an individual spermatozoon was observed microscopically to resume entry into the egg immediately after the addition of a sufficient amount of Mg2+ to the surrounding medium. Neither any change in membrane potential nor an increase in intracellular Ca2+ concentration of the egg was observed after insemination in the absence of Mg2+, although both could be observed after the addition of Mg2+. The sperm heads did not show fluorescence when attached to the surface of an egg previously microinjected with mithramycin A in Mg-free seawater, indicating that there was no connection between the sperm and the egg. Therefore, occurrence of fertilisation potential must be a post-fusional event. These results suggest that Mg2+ are indispensable for fusion between the sperm acrosomal membrane and the egg plasma membrane. PMID- 7874459 TI - Association of cumulus-oocyte complexes with the intrafollicular levels of a blood protein in Bubalus bubalis. AB - The protein pattern of the follicular fluid (FF) and the ultrastructure of the inner cumulus-oocyte complex (COC) has been analysed in single antral follicles (n = 146) of buffalo B. bubalis ovaries. The protein population of FF was fractionated by SDS-PAGE; the resulting pattern was Coomassie stained and processed for densitometry. Comparative analysis of sera and autologous FFs showed a marked difference in the level (measured as the percentage of total proteins) of one 21 kDa polypeptide band, called 'L'. Concentration of L, which was mainly higher in the serum (2.05 +/- 1.5%) than in the surrounding FF (0.98 +/- 0.94%), fluctuated widely in fluids from the same ovary. On gel filtration of FF and SDS-PAGE of the fractions collected, the L polypeptide was found and eluted together with a 36 kDa polypeptide, called 'H', with an exclusion volume lower than that of albumin. The levels of both polypeptides in the eluted fractions were measured by gel densitometry, and the same ratio H/L was found (2:1). These data suggest that H and L are subunits of a complex high-molecular weight protein. The presence of L levels in male sera comparable to those detected in females indicates that this putative protein does not originate in the ovary but is transported from the blood. Moreover, a correlation between the increase in the percentage of Lf (calculated as %L in FF/%L in serum) and atresia was observed. COCs (n = 86) obtained during the collection of the single FF samples were processed for transmission electron microscopy. The ultrastructure of each COC was compared with the SDS-PAGE data of the associated FF. Healthy COCs were found to be related to very low levels of Lf (between 0 and 14% of those measured in serum). COCs with an early atretic ultrastructure undetectable at the dissection microscope, were associated with FFs having Lf levels between 24% and 60%; advanced atresia was associated with Lf values up to 70%. Finally, the acrosome reaction of buffalo precipicitated spermatozoa in vitro was monitored by adding one volume of FF with high (FF+; Lf = 80%) or undetectable (FF-) values of Lf to the sperm suspension.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7874458 TI - A unique expression pattern for a sperm membrane protein during sea urchin spermatogenesis. AB - Specific mRNAs coding for a 63 kDa sperm membrane protein (63-SMP) were localised in Strongylocentrotus purpuratus testis sections using in situ hybridisation techniques. 35S-labelled antisense RNA probes transcribed from a 766 base pair fragment of the gene coding for the 63-SMP hybridised to all spermatogenic cells in the basal germinal epithelia of testicular acini, except the most peripherally located (least differentiated) spermatogonia. No hybridisation to the luminally located mature spermatozoa or somatic cells of the testis was observed. Using monoclonal antibody J17/30 and indirect immunofluorescence techniques, the 63-SMP was localised to the same subset of spermatogenic cells that contain the 63-SMP mRNA, suggesting that expression of this gene is transcriptionally controlled. In combination with previous studies on the expression of sperm histones and sperm binding, these results show that multiple, perhaps sequential, classes of gene activity contribute to the differentiation of sea urchin sperm. PMID- 7874460 TI - In vitro development of morulae from immature caprine oocytes. AB - The effects of medium supplementation with oestrous goat serum and glycoprotein hormones on caprine oocyte maturation in vitro (IVM) were evidenced by proportions of resulting ova completing in vitro fertilisation (IVF) and development to the morula stage. Oocyte-cumulus complexes (OCCs) were harvested in follicular fluid from 2-5 mm diameter follicles. Oocyte maturation took place during 27 h in TCM-199 supplemented with 20% oestrous goat serum, oestradiol-17 beta (1.0 microgram/ml), and either (a) 0.5 microgram FSH/ml, (b) 100 micrograms LH/ml, (c) 100 micrograms LH + 0.5 microgram FSH/ml, (d) 100 micrograms hCG + 0.5 microgram FSH/ml, (e) 0.5 microgram TSH/ml or (f) no added glycoprotein hormone (control). Of 353 immature oocytes cultured in seven experiments, 311 (88.1%) exhibited cumulus expansion at the end of the IVM interval; all normal-appearing OCCs were inseminated. In vitro insemination was with ejaculated sperm treated with heparin (10 micrograms/ml) and caffeine (0.4 microgram/ml). Proportions (%) of inseminated ova that were fertilised (cleaved) and that reached the morula stage after IVM with (a) FSH, (b) LH, (c) LH+FSH, (d) hCG + FSH, (e) TSH and (f) no added glycoprotein hormone were (a) 22/52 (42.3%) and 9/52 (17.3%), (b) 25/54 (46.3%) and 14/54 (25.9%), (c) 52/65 (80.0%) and 26/65 (40.0%), (d) 48/78 (61.5%) and 22/78 (28.2%), (e) 14/54 (25.9%) and 4/54 (7.4%), and (f) 11/50 (22.0%) and 1/50 (2.0%), respectively. All treatments yielded better results than IVM with no added glycoprotein hormone. After IVM with added LH+FSH higher proportions of oocytes were fertilised (p < 0.05), and higher proportions reached the morula stage (p < 0.05) when compared with other treatments. PMID- 7874461 TI - Decomposition of cyanobacterial microcystins by iron(III) chloride. AB - Microcystins RR and LR, which were mainly detected in Japan, were reacted with iron(III) chloride in 0.1N hydrochloric acid. Fifty percent of microcystins RR and LR were immediately decomposed at less than ten minutes, and the decomposition was not dependent on pH (2.0-8.0). The decomposed product was purified by a Sep-Pak C18 cartridge, and chromatographed by a silica gel thin layer. As a result, about eight spots were observed in the decomposed product line, three of which were ninhydrin-negative; the others positive. One of these ninhydrin-negative spots was determined (2S, 3S, 8S)-3-amino-2, 6, 8-trimehyl-10 phenyldeca-4E, 6E-dienoic acid by GC-MS analysis. In addition, the product obtained from the decomposed microcystin LR with iron(III) chloride did not have an acute toxicity. PMID- 7874462 TI - Degradation of propanil by bacterial isolates and mixed populations from a pristine lake. AB - The microbial transformation rates of propanil, a commonly used herbicide, were investigated using water from a pristine lake in northeast Georgia. Microbial degradation rates were measured using natural water microflora, the natural water microflora amended with five bacterial species (Aerobacter aerogenes, Aeromonas hydrophila, Acinetobacter calcoaceticus, Proteus mirabilis, and Aeromonas salmonicida) isolated from the same lake, and the five isolates individually. Transformation rate constants for propanil were compared for the mixed microbial assemblages and isolates at similar initial bacterial concentrations (approximately 5.0 x 10(-3) bacteria/mL). Degradation started within 60 hours and was completed by 160 hours in all experiments. The mean first-order rate constant for natural microflora was -(4.80 +/- 0.620) x 10(-3) h-1. Natural waters amended with the bacterial isolates yielded rate constants ranging from -(0.39 +/- 0.186) x 10(-3) h-1 to -(2.13 +/- 0.029) x 10(-3) h-1 with an overall mean of -(1.63 +/- 0.242) x 10(-3) h-1. After 660 hours following the first amendment of propanil, (i.e., 500 hours after propanil degradation was complete), each sample was again amended with propanil. Subsequent degradation rates ranged from -(21.3 +/- 0.186) x 10(-3) h-1 to -(64.2 +/- 0.786) x 10(-3) h-1 and the mean rate constant was (37.5 +/- 0.922) x 10(-3) h-1. No significant differences were observed between first-order rate constants among isolates following the first or the second addition of propanil. After the second spike, however, the average of rate constants was approximately 20 times greater than that following the first spike. Rates for the individual isolates varied greatly from one isolate to another, ranging from virtually no degradation with A. calcoaceticus to -(21.6 +/- 0.332) x 10(-3) h-1 for the composite treatment of all isolates. PMID- 7874463 TI - Concentration of mercury in hair of Japanese people. AB - This investigation was made to estimate current normal concentrations of total mercury in the hair of Japanese people. Hair samples were collected from 365 healthy volunteers in Tokyo and the surrounding areas from June 1992 to June 1993. Mercury contents in the samples were analyzed by gold amalgam flameless atomic absorption spectrophotometry. The mean of the concentrations of total mercury in the hairs of the males (2.98 ppm, 81 volunteers with an average age of 34.7, age 11 to 73) was higher than that of the females (2.02 ppm, 284 volunteers with an average age of 26.5, age 12 to 82). In both the male and female, the mean of the concentrations of total mercury in hair increased with age up to their thirties, then gradually decreased. The concentrations of total mercury in the hair of females at age 18 to 40 showed greater fluctuation, as compared to those of males in the same age groups. In both males and females, the concentration of total mercury in the hair was higher in volunteers who have a preference to fish in their diet than in those who prefer other foods. In both males and females, there was no positive correlation between the total hair mercury and the place of residence of the volunteer although the total hair mercury (2.30 ppm) of male volunteers who inhabit Ibaragi and Chiba, in eastern part of Tokyo, facing the Pacific Ocean or both the Pacific Ocean and Tokyo Bay, was lower than those (3.30 and 3.25 ppm) of male volunteers of other two areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874464 TI - Concentration of mercury in hair of diseased people in Japan. AB - The purpose of this investigation was to estimate the total hair mercury of diseased people (not including patients of mercury poisoning such as Minamata disease). Hair samples were collected from 133 diseased volunteers in Tokyo and the surrounding areas from Oct. 1992 to June 1993. The total mercury concentrations in the hair of ordinary diseased people (atopic dermatitis, asthma, dementia, cerebral infarct, osteoporosis, hypertension and diabetes) were from 2.08 ppm to 36.5 ppm. Those values were considerably higher than that of healthy people of the same age groups. However, the uptake routes and the metabolic mechanism of high hair mercury concentrations in diseased people are not clear. PMID- 7874465 TI - Chlorinated contaminants in chorio-allantoic membranes from great blue heron eggs at Whidbey Island Naval Air Station. AB - Chorio-allantoic membranes (CAMs) were collected and analyzed for chlorinated hydrocarbons as part of a wildlife toxicology demonstration project at Naval Air Station (NAS) Whidbey Island, Washington, USA. Concentrations of DDT, DDE, DDD, Aroclor 1254, and Aroclor 1260 were found at concentrations below 0.4 ppm for 13 of 14 samples. The low correlations among DDT and its metabolites in CAMs suggest herons are not being exposed to a consistent source of these compounds. Comparison of chlorinated hydrocarbon data for CAMs from three Puget Sound heron colonies, NAS Whidbey, Samish Island and Dumas Bay, indicates contaminant burdens in herons from NAS Whidbey and Samish Island are significantly lower than burdens in herons from Dumas Bay. PMID- 7874466 TI - Effects of benzo(a)pyrene and tetrachlorodibenzo(p)dioxin on fetal dolphin kidney cells: inhibition of proliferation and initiation of DNA damage. AB - Dolphin kidney cells (CDK) were exposed in vitro to benzo(a)pyrene (BaP) in the presence or absence of 2,3,7,8-tetrachlorodibenzo(p)dioxin (TCDD), a cytochrome P450-inducing agent, and/or alpha-naphthoflavone (alpha NF), an inhibitor of cytochrome P450 induction. BaP inhibited mitosis in CDK cells in a dose-dependent manner. TCDD, while inhibiting cell proliferation, did not show a strict dose dependent mode of action. BaP inhibition of mitosis was decreased by alpha NF, which also decreased the inhibitory effects of TCDD on CDK proliferation. BaP treatment initiated both 3H-thymidine incorporation and the increased alkali lability of DNA functions of the initiation of excision repair. Cells pre-treated with TCDD and then exposed to BaP exhibited increased BaP-DNA adduct levels and increased DNA excision repair. These data indicate that dolphin cells metabolized BaP in vitro as a function of cytochrome P450-associated activities, that BaP metabolites covalently bound to cellular DNA and initiated excision repair. Inhibition of the cytochrome P450-mediated metabolism of BaP decreased the BaP associated inhibition of mitosis in dolphin cells. PMID- 7874467 TI - Influence of copper, manganese and pH on the growth and several enzyme activities in mycorrhizal fungus Amanita muscaria. AB - The effects of various concentrations of copper, manganese and pH on the growth and several enzyme activities of mycorrhizal fungus Amanita muscaria were investigated. Cu (5-25 mg l-1) and lower pH (3.0-4.0) strongly inhibited the mycelial growth (dry weight), however, the protein content was not affected evidently. Some enzyme activities were lower as the Cu and Mn concentrations were higher and other enzymes had the maximum values at the specified concentration. The activities of the following enzymes were significantly correlated with the fungal growth after the treatment with Cu: G6PDH, MTLDH and trehalase, and with Mn: G6PDH, MTLDH and alpha-mannosidase respectively. Measurement of these enzyme activities might provide a useful biochemical criterion for the evaluation of the fungitoxicity of soil contaminated by copper or manganese. PMID- 7874468 TI - PCDD/Fs and non-o-PCBs in digested U.K. sewage sludges. AB - Twelve digested sewage sludges from rural and urban waste water treatment works in the north-west of England were analysed for PCDD/Fs and non-o-PCBs. The PCDD/F analysis of eight samples was repeated using high-resolution mass spectrometry, which enabled detection of the lower chlorinated congeners and calculation of TE values. sigma TEQ values for these eight samples ranged from 19-206 ng/kg with the higher values detected in the samples from urban/industrial areas. Examination of the congener/homologue profiles for the more contaminated samples suggests a major input from the use of pentachlorophenol. Archived sewage sludge samples collected and stored from one sewage treatment works in the south of England between 1942 and 1960 were analyzed to gain some insight into temporal trends and possible variations in source inputs. These provide some evidence of changing sources of PCDD/Fs over time and a decline in sigma TEQs since the 1950s. PMID- 7874469 TI - Easy and inexpensive diffusion tests for detecting the assimilation of aromatic compounds by yeast-like fungi. Part I. Assimilation of dihydroxyphenols. AB - A number of easy and inexpensive diffusion tests have been proposed to find microorganisms that are able to decompose aromatic compounds. These tests made it possible to show the assimilation of catechol, resorcinol and hydroquinone by selected yeast-like fungi. The tests may be used to choose highly active strains from culture collections. PMID- 7874470 TI - Bioaccumulation and toxic effects of elevated levels of 3,3',4,4' tetrachloroazobenzene (33'44'-TCAB) towards aquatic organisms. I: A simple method for the rapid extraction, detection and determination of 33'44'-TCAB in multiple biological samples. AB - The polychlorinated aromatic compound 3,3',4,4'-tetrachloroazobenzene (33'44' TCAB) is a contaminant of 3,4-dichloroaniline based herbicides, but there have been no reports of methods for the quantitative determination of 33'44'-TCAB in biological organisms. In this communication we address this knowledge gap by presenting a method for the rapid extraction, detection and determination of 33'44'-TCAB in multiple biological samples based on the alkaline decomposition of the sample followed by alumina cartridge column chromatography and GC-HRMS analysis. PMID- 7874471 TI - Bioaccumulation and toxic effects of elevated levels of 3,3',4,4' tetrachloroazobenzene (33'44'-TCAB) towards aquatic organisms. II: Bioaccumulation and toxic effects of dietary 33'44'-TCAB on the Japanese Medaka (Oryzias latipes). AB - The polychlorinated aromatic compound 3,3',4,4'-tetrachloroazobenzene (33'44' TCAB) is a contaminant of 3,4-dichloroaniline (3,4-DCA) based herbicides, and of agricultural soils. In this study, the Japanese Medaka (Oryzias latipes) was exposed to 0.5-2500 ppm 33'44'-TCAB through its diet. There was a distinct trend towards increased mortality and increased body burdens of 33'44'-TCAB with increasing 33'44'-TCAB charge in the food. At the highest levels of exposure, there was a significant number of excess deaths compared to control groups. PMID- 7874472 TI - Bioaccumulation and toxic effects of elevated levels of 3,3',4,4' tetrachloroazobenzene (33'44'-TCAB) towards aquatic organisms. III: Bioaccumulation and toxic effects of detrital 33'44'-TCAB on the aquatic snail, Indohiramakigai (Indoplanorbis exustus). AB - The polychlorinated aromatic compound 3,3',4,4'-tetrachloroazobenzene (33'44' TCAB) is a contaminant of many 3,4-dichloroaniline (3,4-DCA) based herbicides, and of agricultural soils. In this study, the aquatic snail Indohiramakigai (Indoplanorbis exustus) was exposed to detrital 33'44'-TCAB. The snails absorbed 33'44'-TCAB from their environment, but only to a maximum level of approximately 287 ppb (whole body basis). This level of 33'44'-TCAB did not appear to cause any harmful effects. PMID- 7874473 TI - Erod measurement using post mitochondrial supernatant (pms) in roach (Rutilus rutilus L.), a possible biomonitor for PAH contamination in the freshwater environment. AB - The use of hepatic post-mitochondrial supernatant (pms) as a source of monooxygenase activity in roach following intra peritoneal injection of beta naphthoflavone was investigated. Pms was found to be three times less active than microsomes although the level of induction was similar (9 fold). No effect of dicumarol on Ethoxyresorufin O-deethylase (EROD) measurement using pms was recorded. EROD induction in roach peaked 2-4 days post treatment with beta naphthoflavone. Given the ubiquitous nature and pollution tolerance of roach, their hepatic pms may serve as a convenient biomonitor of PAH contamination in the freshwater environment. Field studies are now underway to investigate this further. PMID- 7874474 TI - Modelling non-equilibrium concentrations of microcontaminants in organisms: comparative kinetics as a function of species size and octanol-water partitioning. AB - From our experience, risk assessment for environmental management and research purposes is in need of models that apply to many of the species we want to protect from many of the microcontaminants released. The traditional one compartment model serves as such a tool during interpretation and extrapolation of information on concentration kinetics. Unfortunately, its non-steady parameters are specific for a combination of a compound and a species. So, one must seriously face the prospect that their values will never be measured for most compounds and species due to experimental, ethical and financial constraints. It was therefore considered worthwhile to relate the main non-steady state parameter, viz. the outflow (elimination, clearance, depuration) rate, to common characteristics of compounds and species. The outflow rate (kout) for persistent organic microcontaminants was correlated to the octanol-water partition ratio of the compound (Kow) and the size of the species (z). The regressions for aquatic invertebrates, fish and warm-blooded animals were kout = (1/(4*10(-3)*Kow + 7*10(-8)) + 5*10(-3))*z-0.36 (n = 53, r2 = 0.45), kout = (1/(4*10(-4)*Kow + 5) + 4*10(-3))*z-0.19 (n = 140, r2 = 0.68) and kout = (1/(3*10(-4)*Kow + 2*10(-5)) + 8*10(-3))* z-0.86 (n = 51, r2 = 0.48) respectively. The correlation was less strong if Kow or z were omitted. In addition to the minimum loss rate for persistent compounds, one may distinguish an excess outflow rate (mainly caused by biotransformation) for less persistent organic microcontaminants. The order of magnitude difference is explored and ways to refine these estimations are discussed briefly. Outflow rates for cadmium and mercury are linked to species size with the same type of function. The internal consistency of the model was verified by calculating inflow rates from calibrated outflow rates and comparing these to independent measurements. Moreover, the constants in the regressions are explained physically and their value is compared with those obtained in ecology for consumption, production and respiration. The exponent that scales these rates to the species size is similar to the regressions for outflow rates obtained here. The model allows estimations for fairly unknown substances or species and it is thought to help refining risk evaluations without extensive experimental or desk studies. As this paper shows that joint application of chemical (Kow) and ecological (z) information yields more accurate estimations, this study contributes to the often advocated integration of both disciplines in ecotoxicology. PMID- 7874476 TI - Drinking water: for human consumption only? The amendment of directive 80/778/EEC parameter 55 in the light of aquatic toxicology. AB - In the current debate on the amendment of the European Drinking Water Directive (80/778/EEC) it is proposed that maximum admissible concentrations for pesticides and related products intended for human consumption shall be based on toxicological evidence. This paper compares limit values for human drinking water, based on mammal toxicology with aquatic toxicity data and water quality objectives for several pesticides proposed for the EC positive list. As aquatic organisms show higher sensitivities to pesticides it is concluded that sustainable water management practises require acknowledgement of ecotoxicological evidence. PMID- 7874475 TI - Solubility and micelle-water partitioning of polychlorinated biphenyls in solutions of bile salt micelles. AB - Experimental data are presented on the enhanced solubilities and micelle/water partition coefficients of 14 polychlorinated biphenyls (PCBs) in solutions of the bile salts sodium taurocholate (TC) and sodium taurodeoxycholate (TDC) below and above the critical micellar concentration (CMC). Solubilities of PCBs in micellar solutions above the CMC depend linearly on bile salt concentration and the solubility enhancement is up to four orders of magnitude. PCB partition coefficients (log Kmw) are independent of bile salt concentrations and are systematically higher in solutions of TDC than in solutions of TC, ranging from 4.26 to 6.24 and from 3.89 to 5.89 respectively. The partitioning behavior of the pertinent extremely hydrophobics between the aqueous and micellar phases is not completely comparable with simple organic solvent/water systems and the correlation between log Kow and log Kmw is non-linear. PMID- 7874477 TI - Effect of herbicides on nitrogen fixation (C2H2 reduction) associated with rice rhizosphere. AB - In a field study nitrogenase activity associated with rice rhizosphere was differently influenced by the applied herbicides. Pretilachlor at two application levels had no effect on nitrogenase activity while butachlor and benthiocarb exerted marginal stimulation. Cinmethylin consistently stimulated nitrogenase activity throughout the plant growth period. Anilofos when applied singly had no substantial effect on nitrogenase activity but in combination with 2,4-D the activity was enhanced. Populations of anaerobic nitrogen-fixing bacteria and Azospirillum sp. and Azotobacter sp. were stimulated in such a combination. PMID- 7874478 TI - Organelle movement. Dynactin: portrait of a dynein regulator. AB - Recent studies of dynactin, a protein complex implicated in regulating the cytoplasmic motor protein dynein, reveal that the complex contains a specialized actin filament and may also interact with microtubules. PMID- 7874479 TI - Sex determination. Turning on sex. AB - The orphan nuclear receptor, steroidogenic factor 1, is central to the differentiation of male and female mammalian gonads. It controls the fate of the initially bipotential gonad as well as later male-specific functions. PMID- 7874480 TI - Topoisomerases. In one gate, out the other. AB - The ability of type II DNA topoisomerases to pass one DNA double helix through another can be explained by a mechanism involving two gates in the enzyme structure. PMID- 7874481 TI - Caged neurotransmitters. Shedding light on neural circuits. AB - The ability to locally activate neurons in living brain slices by using light to release 'caged' neurotransmitter allows the organization and development of neural circuits to be studied at a hitherto impossible level of detail. PMID- 7874482 TI - Plant regulators. Insensitivity is in the genes. AB - The cloning of loci determining abscisic acid insensitivity in Arabidopsis has identified a phosphatase and a transcriptional activator that mediate responses to abscisic acid and so regulate plant growth and development. PMID- 7874483 TI - Thrombopoiesis. Capturing the unicorn. AB - The elusive factor that stimulates megakaryocytes to produce platelets has at last been found; as well as its physiological interest, this factor- thrombopoietin--may be of considerable therapeutic importance. PMID- 7874484 TI - Vacuolar sorting. Tracking down an elusive receptor. AB - The receptor that sorts carboxypeptidase Y for transport to the vacuole in yeast has recently been identified; how vacuolar sorting is regulated is far from understood, but an intriguing model has been proposed. PMID- 7874485 TI - Familial breast cancer. BRCA1 down, BRCA2 to go. AB - The breast cancer susceptibility gene BRCA1 has been cloned and a second susceptibility gene, BRCA2, chromosomally mapped; will most breast and ovarian cancer turn out to be familial? PMID- 7874486 TI - Transgenic mice. Fade to grey. AB - Expression of different amounts of tyrosinase from varying numbers of transgenes rescues the coat colour and eye pigmentation of albino mice in an approximately dose-dependent manner. PMID- 7874487 TI - Phage tailspike protein. A fishy tale of protein folding. AB - The crystal structure of bacteriophage P22 tailspike protein reveals a striking fold with a distinctive, fish-like appearance, and helps explain many of the properties of this unusual molecule and its folding pathway. PMID- 7874488 TI - Cell differentiation. Muscle escapes from a jelly mould. AB - Striated muscle cells from the medusa of the jellyfish Podocoryne show remarkable plasticity; vertebrate myotubes are less plastic, but can re-enter the cell cycle in the absence of the retinoblastoma protein. PMID- 7874489 TI - Signal transduction. Just another signalling pathway. AB - The recently identified JAK-STAT signal transduction pathway plays a major role in signalling the arrival of cytokines at the cell surface and can, in part, account for the pleiotropic and redundant effects of cytokines. PMID- 7874490 TI - Neurodegenerative disease. Oxidative stress and motorneuron disease. AB - Transgenic mice carrying mutated Cu/Zn superoxide dismutase genes provide insights into the pathogenesis of human motorneuron diseases and may be useful as models in the development and testing of therapies. PMID- 7874491 TI - Plant development. The SECrets of Arabidopsis embryogenesis. AB - The study of plant embryogenesis has come of age with the cloning of the first gene controlling pattern formation in the Arabidopsis embryo. PMID- 7874492 TI - Growth factors. A scattering of factors. AB - Hepatocyte growth factor/scatter factor is a multifunctional growth factor with varied properties: more and more polypeptide factors are being discovered that share these characteristics. PMID- 7874493 TI - Partners make patterns in morphogenesis. PMID- 7874494 TI - Causes of cricket synchrony. PMID- 7874495 TI - Muscle development in the four-winged Drosophila and the role of the Ultrabithorax gene. AB - BACKGROUND: In the fruitfly Drosophila melanogaster, segment identity is specified by the homoeotic selector genes of the bithorax and Antennapedia complexes. The functions of these genes in the segmental specification of the Drosophila ectoderm have been well studied, but their roles in muscle development have been relatively poorly investigated. Recent experiments have strongly suggested that homeotic selector genes are directly involved in one aspect of mesodermal patterning during Drosophila embryogenesis. But muscle development is a complex process, requiring for its completion the correct positioning of the epidermis, the nervous system and the developing muscles in a segment-specific manner. Many aspects of homeotic selector gene function in this process remain to be understood. RESULTS: In flies that are homozygous for three mutant alleles (anterobithorax, bithorax3, postbithorax) of the Ultrabithorax gene, the third thoracic segment (T3) is transformed towards the second (T2). The adults have two pairs of wings, but the homeotically transformed T3 (HT3) has only rudimentary indirect flight muscles. We used the 'four-winged' fly to study the role of homeotic selector genes in the development of the indirect flight muscles, which we classify into four 'events'. First, the determination of the segment-specific pattern of myoblasts in the larval thorax; second, the specific pattern of migration of myoblasts during metamorphosis; third, the fusion of myoblasts to form adult indirect flight muscles and fourth, the development of the branching pattern of adult motor innervation. Our study shows that the segmental identity of the epidermis determines the segment-specific pattern and number of myoblasts on the larval discs, and the pattern of their migration during metamorphosis. The segmental identity of the mesoderm, however, is crucial for the fusion of myoblasts to form indirect flight muscles, and also influences the branching pattern of innervation of indirect flight muscles. CONCLUSIONS: Segmental information expressed in the ectoderm, and the autonomous function of homeotic selector genes in the mesoderm, are both required for the complete development of indirect flight muscles. PMID- 7874496 TI - Use of an oriented peptide library to determine the optimal substrates of protein kinases. AB - BACKGROUND: Phosphorylation by protein kinases is an important general mechanism for controlling intracellular processes, and plays an essential part in the signal transduction pathways that regulate cell growth in response to extracellular signals. A great number of protein kinases have been discovered, and the identification of their biological targets is still a very active research area. Protein kinases must have the appropriate substrate specificity to ensure that signals are transmitted correctly. Previous studies have demonstrated the importance of primary sequences within substrate proteins in determining protein kinase specificity, but efficient ways of identifying these sequences are lacking. RESULTS: We have developed a new technique for determining the substrate specificity of protein kinases, using an oriented library of more than 2.5 billion peptide substrates. In this approach, the consensus sequence of optimal substrates is determined by sequencing the mixture of products generated during a brief reaction with the kinase of interest. The optimal substrate predicted for cAMP-dependent protein kinase (PKA) by this technique is consistent with the sequences of known PKA substrates. The optimal sequences predicted for cyclin dependent kinases (CDKs) cyclin B-Cdc2 and cyclin A-CDK2 also agree well with sites thought to be phosphorylated in vivo by these kinases. In addition, we determined the optimal substrate for SLK1, a homologue of the STE20 protein serine kinase of hitherto unknown substrate specificity. We also discuss a model incorporating the optimal cyclin B-Cdc2 substrate into the known crystal structure of this kinase. CONCLUSIONS: Using the new technique we have developed, the sequence specificity of protein kinases can rapidly be predicted and, from this information, potential targets of the kinases can be identified. PMID- 7874497 TI - The sequence complexity of exons trapped from the mouse genome. AB - BACKGROUND: A central issue in genome analysis is the identification and characterization of coding regions. Estimating the coding complexity of vertebrate genomes by measuring the kinetic complexity of mRNA populations and by sequence analysis of cDNAs is limited by the fact that any given source of mRNA represents a very biased sample of all genes. Exon trapping is a method that enables the identification of genes irrespective of their transcriptional status. RESULTS: Exons were trapped from the entire mouse genome, and the resulting fragments cloned. About 7% of a random sample of exons taken from this library have significant structural homology or sequence similarity to previously sequenced genes. Using cDNAs derived from several stages of mouse development, evidence for expression of about 62% of this sample of exons was found. These data suggest that the great majority of 'exons' in the library are derived from genes. We estimate that the fraction of the genome contained in trapped exons is 2.4%; this corresponds to a sequence complexity of about 72 megabases. CONCLUSIONS: The library of exons trapped from the entire mouse genome probably represents one of the least biased and most comprehensive libraries of mouse coding regions, and should therefore prove very useful for finding genes during genome mapping and sequencing. PMID- 7874498 TI - Evidence against the existence of the purported Saccharomyces cerevisiae PKC2 gene. AB - BACKGROUND: The existence of a Saccharomyces cerevisiae gene encoding a novel isoform of protein kinase C was reported recently in this journal. RESULTS: We demonstrate here that, firstly, the purported PKC2 gene does not reside at the chromosomal location to which it was assigned; secondly, it does not exist as a contiguous sequence in the S. cerevisiae genome; thirdly, some of its reported sequences do exist within other yeast genes; and fourthly, some of its reported sequences, encoding regions of the predicted protein related to protein kinase C, do not exist in any context in the yeast genome. CONCLUSIONS: We conclude from these studies that the PKC2 gene is a composite construction of unrelated yeast and non-yeast sequences. PMID- 7874499 TI - Glycobiology. The beginning of a sweet tale. AB - The diversity of complex carbohydrates has fascinated and frustrated glycobiologists for years. Now, manipulating oligosaccharide composition in the embryo promises new insights into their developmental functions. PMID- 7874500 TI - An indirect projection from the nucleus of the solitary tract to the central nucleus of the amygdala via the parabrachial nucleus in the rat: a light and electron microscopic study. AB - The morphological basis of how visceral information from the nucleus of the solitary tract (NTS) is relayed from the parabrachial nucleus (PBN) to the central nucleus of the amygdala (Ce) was studied at the light and electron microscopic levels using the anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L), kainic acid degeneration, and retrograde tracing with horseradish peroxidase (HRP). After injection of PHA-L into the caudal NTS, anterogradely labeled fibers and terminals were predominantly distributed in the external lateral (el) and central lateral (cl) subnuclei of the PBN. After injection of HRP into the Ce, retrogradely labeled neurons in PBN were mainly distributed in the same areas. In double-labeling experiments, there was a clear overlap between neuronal elements labeled with HRP and PHA-L in the el and cl. At the electron microscopic level, the PHA-L-labeled axon terminals from the NTS mainly contained spherical agranular synaptic vesicles and formed asymmetric contacts with the postsynaptic dendrites or dendritic spines in PBN. After the lesioning agent kainic acid was injected into the NTS and HRP deposited in the Ce, it was found the afferent fibers from the NTS made direct synaptic contact with the lateral PBN neurons which in turn projected to Ce. Such evidence adds to our growing knowledge of regulation of visceral function in central nervous system and would be likely helpful for understanding the important roles of the NTS, PBN and Ce in the central control of cardiovascular, respiratory and gastrointestinal functions. PMID- 7874501 TI - Ketamine increases the striatal N-[11C]methylspiperone binding in vivo: positron emission tomography study using conscious rhesus monkey. AB - A system for positron emission tomography study of conscious monkeys was newly developed. By use of this system in combination with a microdialysis technique, the effect of ketamine on the binding and release of dopamine was investigated. The administration of ketamine (5 mg/kg) caused sedation accompanied by psychotic symptoms such as nystagmus and stereotyped movements of extremities. During this psychotomimetic period produced by ketamine, a significant increase in the accumulation of the dopamine D2 receptor ligand N-[11C]methylspiperone was observed in the striatum compared with the level in the conscious state, while no significant change was observed in the frontal cortex and cerebellum. In contrast to the use of ketamine as the anesthetic, pentobarbital (25 mg/kg), which produced deeper anesthesia but no psychotic symptoms, caused a decrease in the accumulation of N-[11C]methylspiperone in the striatum. Kinetic analysis, conducted by a graphical method, revealed that the value of the association constant (K3) for N-[11C]methylspiperone binding in the striatum was increased to approximately 130% by ketamine and decreased to approximately 70% by pentobarbital compared with the control values. Furthermore, the release of dopamine from the striatum measured by microdialysis was not affected by ketamine anesthesia. These results indicate that ketamine facilitates striatal dopaminergic neurotransmission through increasing the binding activity of dopamine D2 receptors in the striatum, and suggest that these changes may be related to the psychotomimetic behavioral symptoms of this drug. PMID- 7874502 TI - Effects of gliosis on dopamine metabolism in rat striatum. AB - Neuroimplantation is inevitably accompanied by gliosis. Although graft-induced trophic effects on host neurons may be mediated by glial cells, the effects of gliosis on dopamine (DA) metabolism remains unclear. To examine these effects, basic fibroblast growth factor (bFGF) was directly infused into the striatum of 12 male rats (250-280 g). One week later, substantial gliosis was demonstrated in the infused striatum by immunochemical staining for glial fibrillary acidic protein (GFAP) and quantified by GFAP Western blot analysis. One week after bFGF infusion, extracellular DA and its metabolites were measured by in vivo microdialysis using HPLC. Infusion of L-dopa through the dialysis probe resulted in a 60% reduction in the L-dopa-induced DA peak in the gliotic striatum compared with the normal side. After L-dopa infusion, dihydroxyphenylacetic acid (DOPAC) levels were similar between the gliotic and normal striatum. In contrast, homovanillic acid (HVA) levels were 26% higher in the gliotic striatum. Enzyme assays demonstrated that aromatic L-amino acid decarboxylase activity was unchanged in the gliotic striatum, but both MAO-A and MAO-B activities increased by 23% and 21%, respectively. These results suggest that the reduced striatal DA peak in the gliotic striatum after L-dopa administration was due to accelerated DA catabolism through enhanced MAO activity. The bFGF-induced striatal gliosis may serve as a model to study neurotransmitter metabolism in the gliotic brain caused by disease processes, aging, or tissue grafting. PMID- 7874503 TI - Reduced retinal activity increases GFAP immunoreactivity in rat lateral geniculate nucleus. AB - Dynamic regulation of astrocytic processes by the electrical activity of local neurons has been previously described in chick cochlear nucleus. The present study extends this observation by showing that astrocytes in the rat lateral geniculate nucleus (LGN) also increase their immunoreactivity for glial fibrillary acidic protein (GFAP) soon after deprivation of afferent visual neuronal activity. Within 6 h of enucleation, which eliminates a major source of afferent input to the contralateral LGN, GFAP immunoreactivity increases relative to the ipsilateral LGN. A similar increase in GFAP immunoreactivity can be induced by intraocular injections of tetrodotoxin, demonstrating that a reversible manipulation of optic nerve electrical activity is sufficient to regulate LGN astrocytes. This rapid response to activity deprivation is less dramatic than the gliotic reaction observed 3 weeks following deafferentation, by which time afferent terminals have degenerated. These results support the notion that regulation of astrocytic processes by neural activity may play an important role in activity-dependent synaptic regulations in the various sensory systems of vertebrates. PMID- 7874504 TI - Effects of funnel web spider toxin on Ca2+ currents in neurohypophysial terminals. AB - Funnel web spider toxin (FTX) is reportedly a specific blocker of P-type Ca2+ channels. The effects of FTX on the Ca2+ currents of isolated neurohypophysial nerve terminals of the rat were investigated using the 'whole-cell' patch-clamp technique. Both the transient and long-lasting Ca2+ current components were maximally elicited by depolarization from a holding potential equal to the normal terminal resting potential (-90 mV). Externally applied FTX inhibited the high voltage-threshold, transient component of the Ca2+ current in a concentration dependent manner, with a half-maximal inhibition at a dilution of approximately 1:10000. FTX also shifted the peak current of the I-V relationship by +10 mV. The long-lasting Ca2+ current component, which is sensitive to L-type Ca2+ channel blockers, was insensitive to FTX. The transient current, which is sensitive to omega-conotoxin GVIA, was completely blocked by FTX. These results suggest that there could be a novel, inactivating Ca2+ channel in the rat neurohypophysial terminals which is affected by both N-type and P-type Ca2+ channel blockers. PMID- 7874505 TI - Brain alpha erythroid spectrin: identification, compartmentalization, and beta spectrin associations. AB - Using isoform and subunit specific antibodies we have determined the presence, localization, and beta spectrin associations of alpha erythroid spectrin, alpha SpI sigma*, as well as alpha non-erythroid spectrin, alpha SpII sigma 1, in mouse brain. Peptide specific antibodies against unique sequences within the beta SpII sigma 1, non-erythroid beta spectrin isoform, and within beta SpI sigma 1, erythrocyte beta spectrin isoform were used to compare the immunolocalization of beta spectrin subunit isoforms with that of alpha spectrin subunit isoforms and to immunoprecipitate spectrin tetramers in order to identify the subunit components by immunoblot analysis. The specificity and sensitivity of antibodies for isoform specific alpha and beta subunits was determined by immunodot and immunoblot methods. Immunohistochemical analyses indicated that beta SpI sigma 2 is located in neuronal somata and dendrites in mouse cerebellum. beta SpII sigma 1 is located in the medullary layer, chiefly composed of axonal tracts. Parallel immunohistochemical analysis with antibodies for the alpha and beta spectrin isoforms revealed that antibodies specific for the alpha subunit of erythrocyte spectrin (alpha SpI sigma 1) localized antigen to the somata and dendrites of cerebellar granule cell neurons, a pattern similar to that for the localization of the erythroid beta subunit (beta SpI sigma 2). In contrast antibodies specific for the non-erythroid alpha subunit (alpha SpII sigma 1) localized antigen to axons in the cerebellum corresponding to the pattern for the non-erythroid beta subunit (beta SpII sigma 1). The distinct localization of antigens by antisera which recognize either the alpha subunit of red blood cell spectrin or the alpha subunit of non-erythroid brain spectrin, together with the correspondence of their localization with appropriate beta subunits, clearly indicate that brain contains at least two species of spectrin each with distinct alpha and beta subunits. Immunoprecipitation experiments of cerebellar extracts using beta spectrin peptide specific antibodies followed by immunoblotting analysis confirmed the association of an erythroid alpha subunit isoform with a beta erythroid subunit isoform, as well as the association of non-erythroid alpha and beta subunits. In addition the immunoblot analysis of the immunoprecipitated material suggested there are minor populations of various hybrid tetramers in brain consisting of mixed erythroid and non-erythroid subunits. In summary these data collectively demonstrate that in mouse brain there are at least two alpha spectrin subunits, one erythroid alpha SpI sigma* and one non-erythroid alpha SpII sigma 1; these associate with an erythroid beta SpI sigma 1, and a non erythroid beta SpII sigma 1 in the cerebellum of mouse.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7874506 TI - Prostaglandin E2 protects cultured cortical neurons against N-methyl-D-aspartate receptor-mediated glutamate cytotoxicity. AB - The effects of prostaglandin (PG) E2 on glutamate-induced cytotoxicity were examined using primary cultures of rat cortical neurons. The cell viability was significantly reduced when cultures were briefly exposed to either glutamate or N methyl-D-aspartate (NMDA) then incubated with normal medium for 1 h. Similar cytotoxicity was observed with the brief application of ionomycin, a calcium ionophore, and S-nitrosocysteine, a nitric oxide (NO)-generating agent. PGE2 at concentrations of 0.01-1 microM dose-dependently ameliorated the glutamate induced cytotoxicity. PGE1, butaprost, an EP2 receptor agonist, and 8-bromo-cAMP were also effective in protecting cultures against glutamate cytotoxicity. By contrast, neither 17-phenyl-omega-trinor-PGE2, an EP1 receptor agonist, nor M&B 28767, an EP3 receptor agonist, affected glutamate-induced cytotoxicity. NMDA induced cytotoxicity was ameliorated by PGE2, butaprost, MK-801, N-omega-nitro-L arginine, a NO synthase inhibitor, and hemoglobin, which binds NO. These agents excluding MK-801 ameliorated the ionomycin-induced cytotoxicity. The cytotoxicity induced by S-nitrosocysteine was prevented only by hemoglobin but not by the other agents including PGE2. These findings indicate that PGE2 protects cultured cortical neurons against NMDA receptor-mediated glutamate neurotoxicity via EP2 receptors. EP2 receptor stimulation may suppress a step in NO formation triggered by Ca(2+)-influx through NMDA receptors. PMID- 7874507 TI - Modulation of prolactin receptors in the rat hypothalamus in response to changes in serum concentration of endogenous prolactin or to ovine prolactin administration. AB - Specific binding of 125I-labeled rat prolactin (125I-rat PRL) to hypothalamic membranes was studied in Sprague-Dawley rats after ovine PRL administration and in relation to rat PRL serum variations induced by ectopic pituitary implants or by drugs which stimulate (domperidone) or inhibit (bromocriptine) PRL release. Repeated treatments with ovine PRL markedly increased specific binding values of 125I-rat PRL to hypothalamic membranes of female rats. Repeated treatments with domperidone also increased specific PRL binding in the hypothalamus. This effect was associated with an increase in PRL serum levels. Similar results were obtained in male rats after renal pituitary implants which resulted in a state of chronic hyperprolactinaemia. In contrast, a subchronic treatment with bromocriptine decreased specific PRL binding in the hypothalamus and concomitantly caused a sharp reduction in PRL serum levels. Scatchard analysis of data obtained from competition curves showed that the variations in the level of PRL binding to hypothalamic membranes were related to the number of PRL binding sites but not to the dissociation constant (Kd), which was unaffected by different treatments or by pituitary implantation. These results demonstrate a correlation between circulating concentrations of PRL and number of its receptors in the rat hypothalamus and give further support to the hypothesis that these binding sites may have a specific functional role in regulating the homeostasis of pituitary PRL secretion. PMID- 7874508 TI - Activity in the human primary motor cortex related to ipsilateral hand movements. AB - In two studies with positron emission tomography (PET), we found that somatosensory discrimination of length activated the ipsilateral MI, but somatosensory discrimination of shape did not. This occurred even though both tasks required the exclusive use of distal finger and hand movements which were also very similar in both tasks. The activation of the ipsilateral MI was correlated with activations of the premotor cortex in the other hemisphere, the prefrontal cortex and the posterior cingulate cortex, indicating that these areas together with the ipsilateral MI constitute a task-related active network. PMID- 7874509 TI - Neonatal exposure to estradiol prevents the expression of ovarian hormone-induced luteinizing hormone and prolactin surges in adulthood but not antecedent changes in neuropeptide Y or adrenergic transmitter activity: implications for sexual differentiation of gonadotropin secretion. AB - Sex differences in adult patterns of mating behavior and gonadotropin secretion in rats are determined in part by the presence or absence of gonadal steroids during a perinatal critical period. For example, male rats and female rats exposed neonatally to androgen do not exhibit LH surge patterns when treated appropriately with ovarian hormones in adulthood, and there is evidence that this may be due to a failure of ovarian hormones to activate the hypothalamic neuronal systems that stimulate LH secretion in such animals. Because considerable evidence suggests that estradiol formed centrally from testosterone is responsible for the permanent defeminization of mating behavior and gonadotropin secretion, the present studies compared normal females with normal males and with females treated neonatally with estradiol on the ability of ovarian hormones to induce several important neurochemical changes antecedent to the LH surge, including changes in neuropeptide Y (NPY) and LH-releasing hormone (LHRH) concentrations in the median eminence, as well as changes in turnover rates for catecholamine transmitters in the medial basal hypothalamus and medial preoptic area. Normal ovariectomized female rats responded to sequential treatment with estradiol followed by progesterone with afternoon LH and prolactin (PRL) surges, and with sequential accumulation followed by decline in concentrations of LHRH and NPY in the median eminence prior to the LH surge. In addition, administration of progesterone increased the turnover rates of norepinephrine (NE) and epinephrine (EPI) in the arcuate-median eminence region of normal females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874510 TI - Fos protein expression in the nucleus of the solitary tract in response to intestinal nutrients in awake rats. AB - Nutrients in the intestine inhibit food intake via an action on the vagal afferent pathway. The aim of the present study was to use immunochemical detection of Fos protein-like immunoreactivity (FLI) in the brainstem to trace the neuronal pathways activated by intestinal nutrients. Perfusion of the intestine of awake rats via an indwelling duodenal catheter with iso-osmotic mannitol, hydrochloric acid or casein hydrolysate had no effect on the number of FLI neurons in the nucleus of the solitary tract (NTS). Lipid emulsion (20%) and 2.7 M glucose significantly increased the number of immunopositive cells in the NTS. There was a significant increase in the number of immunopositive cells from caudal to rostral NTS. Nutrients effective at decreasing food intake (carbohydrate and fat) produced significant increases in Fos-like immunopositive cells in the NTS. PMID- 7874511 TI - An amyloid beta-protein fragment, A beta[12-28], equipotently impairs post training memory processing when injected into different limbic system structures. AB - Previously, amyloid beta-protein (A beta) fragments 1-28, 12-28 and 12-20 were found to impair retention in mice when injected intracerebroventricularly after footshock active avoidance training. We now have measured the dose-dependence of amnestic effects of peptide 12-28 stereotactically injected into amygdala, caudate, hippocampus, mammillary bodies and septum, which limbic structures are known to be involved in memory processing and into the medial thalamus, which largely is involved in sensory processing during training. Peptide 12-28 impaired retention with remarkably similar efficacy when injected into limbic structures but was not at all amnestic upon thalamic injection. Present results together with those in the literature lead us to suggest that A beta may exert dysregulatory cognitive effects by incoordination of K(+)-channel function in neurons, glia and endothelial cells. PMID- 7874512 TI - Cortical cholinergic deafferentation following the intracortical infusion of 192 IgG-saporin: a quantitative histochemical study. AB - The immunotoxin 192 IgG-saporin has been hypothesized to selectively lesion cholinergic neurons that bear the low-affinity p75 nerve growth factor (NGF) receptor. To evaluate the usefulness of this toxin in studies intended to determine the functions of cholinergic afferents of cortical areas, relatively small concentrations and volumes of the immunotoxin (0.01-0.05 micrograms/0.5-1.0 microliters) were infused into cortical areas of one hemisphere of rats, while the vehicle was infused into homologous areas of the contralateral hemisphere. The effects of these infusions on the density of cortical acetylcholinesterase (AChE)-positive fibers and of normal fibers (as revealed by a reduced silver stain) were quantified. The infusion of the immunotoxin did not produce local gliosis in excess of the gliosis resulting from the infusion of vehicle. When compared with the frontoparietal cortex of the intact hemisphere, the number of cortical AChE-positive fibers was reduced by 36-39% and the density of the silver stained fibers was decreased by 20-25%. While the loss of AChE-positive fibers and silver-stained fibers correlated significantly in layers V/VI, a linear regression analysis suggested that the magnitude of the loss of AChE-positive fibers was greater than would be predicted on the basis of the residual density of normal fibers. Thus, the data suggest that infusions of 192 IgG-saporin into the cortex did not result in the loss of non-cholinergic afferents. Intracortical infusions of relatively small concentrations and volumes of 192 IgG-saporin appear to provide a useful approach for the examination of the functions of cholinergic inputs to specific cortical regions. PMID- 7874513 TI - Intracerebroventricular injection of prostaglandin E2 induces thermal hyperalgesia in rats: the possible involvement of EP3 receptors. AB - To determine what types of prostanoid receptors are involved in the central effect of prostaglandin E2 (PGE2) on nociception, we administered PGE2 and its agonists, i.e., 17-phenyl-omega-trinor PGE2 (an EP1 receptor agonist), butaprost (an EP2 receptor agonist), 11-deoxy PGE1 (an EP2/EP3 receptor agonist, EP2 >> EP3) and M&B28767 (an EP3 receptor agonist) into the lateral cerebroventricle (LCV) of rats and observed the changes of paw-withdrawal latency on a hot plate. The LCV injection of PGE2 (10 pg/kg-10 ng/kg), 11-deoxy PGE1 (100 pg/kg-10 ng/kg) and M&B28767 (1 pg/kg-100 pg/kg) produced a significant reduction in the paw withdrawal latency. The maximal reduction was observed 15 min after the LCV injection of these drugs. Neither 17-phenyl-omega-trinor PGE2 (1 pg/kg-1 microgram/kg) nor butaprost (1 pg/kg-100 microgram/kg) induced any significant changes in the paw-withdrawal latency. The LCV injection of PGE2 (1 microgram/kg) and 17-phenyl-omega-trinor PGE2 (50 micrograms/kg) increased the latency only 5 min after LCV injection. These findings indicate that the LCV injection of PGE2 induces thermal hyperalgesia through EP3 receptors and analgesia through EP1 receptors by its central action in rats. PMID- 7874514 TI - Influences on the gamma-muscle-spindle system from muscle afferents stimulated by increased intramuscular concentrations of arachidonic acid. AB - There is evidence that static muscular contractions induce a release of arachidonic acid (AA) in the working muscle and that increased concentration of AA in a muscle increases the discharge rate of a subpopulation of groups III and IV muscular afferents. It is also known that activity in groups III and IV muscle afferents may activate gamma-motoneurones to both homo- and heteronymous muscles. The aim of the present study was to investigate if increased concentration of AA in one muscle may influence the activity in primary and secondary muscle spindle afferents (MSAs) from the chemically affected muscle and from surrounding muscles, via fusimotor reflexes. The experiments were made on five cats anaesthetized with alpha-chloralose. The triceps surae (GS) and the posterior biceps and semitendinosus (PBSt) muscles were subjected to sinusoidal stretches. Simultaneous recordings of 2-12 MSAs from these muscles were made and the mean rate of firing and the modulation for each MSA were determined. Responses of 36 MSAs (17 PBSt and 19 GS) were recorded. The responsiveness of the MSAs to injections of AA (0.3-1.0 mg; 0.3-1 ml) was 86% (n = 36) for injections into the arterial supply of the ipsilateral GS muscle and 45% (n = 20) for injections to the contralateral GS muscle. Out of 14 secondary MSAs, only one was unresponsive to ipsilateral AA injections while two of eight were unresponsive to contralateral AA injection. The majority of responses were compatible with predominantly static or mixed dynamic and static fusimotor activation. None of the effects were compatible with inhibition of fusimotor activity. The duration of the effects were usually 2-4 min. However, on some occasions the elevations in MSA activity persisted for up to 1 h. Local anaesthesia of the nerve to the injected muscle always abolished the effects of the injections and control injections of the solution in which the AA was dissolved were ineffective in changing the MSA responses. I.v. injections occasionally induced effects on the MSAs, but such effects were significantly different from those caused by close arterial muscle injections. Thus, increased concentration of AA may excite primary and secondary MSAs from homo- as well as heteronymous muscles, including contralateral muscles, most probably via fusimotor reflexes evoked by activity in chemosensitive muscle afferents. PMID- 7874515 TI - The local cerebral metabolic effects of morphine in rats exposed to escapable footshock. AB - The 2-deoxy-D-[1-14C]glucose (2-DG) method was used to examine the effects of morphine sulfate (MS) on local cerebral metabolic rates for glucose (LCMRglu) in male F-344 rats required to turn a wheel manipulandum in order to escape from nociceptive footshock. Four groups of rats were studied: control-saline, control MS, footshock-saline and footshock-MS. All animals were administered MS (4 mg/kg, s.c.) or saline 7 days, 3 days and 10 min prior to the start of the 2-DG experiment. In agreement with its well-known effect on the emotional component of pain, MS administered to rats exposed to footshock caused a significant decrease in LCMRglu compared to footshock-saline rats in limbic structures such as the diagonal band of Broca, lateral septum, bed nucleus of the stria terminalis, horizontal limb of the diagonal band, habenular complex and medial amygdala. Additionally, two components of the midline thalamus with extensive connections with the limbic system, the paraventricular and paratenial thalamic nuclei, were similarly affected by morphine. Footshock caused an overall increase in cerebral metabolism as 52 of 73 measured structures demonstrated increases in activity compared to saline control; however, statistically significant effects in specific structures were limited. These results identify limbic and midline thalamic structures important in morphine-induced analgesia and indicate that footshock tends to have a generalized stimulatory effect on LCMRglu. PMID- 7874516 TI - The relationship between MRNA levels and the locomotor response to novelty. AB - Differences in behavioral and neurochemical responses to drugs of abuse and environmental stress have been observed between rats that have a greater locomotor response in a novel environment (high responders: HR) compared to those that have a low response to novelty (low responders: LR). This study examined nuclei associated with the nigrostriatal and mesolimbic systems for differences in mRNA content between HR and LR using Northern blot analysis. These brain regions were chosen because of their role in both drug abuse and stress responses. The mRNAs examined code for either peptide transmitters that interact with the dopaminergic system or components of the dopaminergic system that have not been previously examined for differences between HR and LR. HR rats had approximately 50% lower levels of mRNA for beta-preprotachykinin (PPT) in the core of the nucleus accumbens (NACC) compared to LR. No differences between HR and LR in mRNA levels for dynorphin (DYN), preproenkephalin (PPE), glutamic acid decarboxylase (GAD) or neurotensin (NT) were observed in the core of the NACC. In the shell region of the NACC, HR exhibited a 25% reduction in the level of mRNA for NT compared to LR. No differences between HR and LR in mRNA levels for PPT, DYN, PPE or GAD were observed in the shell of the NACC. In the medial frontal cortex and the dorsal striatum, no differences between HR and LR in mRNA levels for PPT, DYN, PPE, GAD or NT were found. In the substantia nigra and ventral tegmental area no differences between HR and LR in mRNA levels for tyrosine hydroxylase, GAD, cholecystokinin, or NT were noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874517 TI - Immunocytochemical evidence that quisqualate is selectively internalized into a subset of hippocampal neurons. AB - Quisqualic acid (QUIS) has been shown to interact with several glutamate receptor subtypes and uptake sites. We have previously demonstrated that a brief exposure of hippocampal cells to QUIS sensitizes them to depolarization by the alpha-amino omega-phosphonate analogues of glutamate, AP4, AP5, and AP6. This QUIS-induced sensitization is accompanied by the active uptake of QUIS into hippocampal slices. In order to localize the sites of QUIS uptake into rat hippocampal slices, a polyclonal antibody against QUIS was raised in rabbits. Utilizing immunocytochemical techniques, we have identified immunoreactive axons and dendrites after brief exposure times to QUIS, and perikarya after longer exposure times to QUIS. The intensity of the QUIS immunoreactivity increased as the exposure time to QUIS increased. QUIS immunoreactivity was primarily found in stratum oriens and stratum radiatum, of regions CA1, CA2, and CA3 of the hippocampus as well as in the hilus and molecular layer of the dentate gyrus. The distribution and morphology of QUIS immunoreactive cells appeared to be similar to those of GABAergic interneurons. Glial fibrillary acidic protein (GFAP) did not co-localize with the QUIS-internalizing cells suggesting that they are not glia. Ultrastructural analysis revealed QUIS immunoreactive profiles within the stratum radiatum. Immunostained profiles at both the light and EM levels appeared, in many cases, to be swollen and showed signs of degeneration. Such changes were only evident in tissue exposed to QUIS. These data demonstrate that QUIS is taken up by a select group of neurons in the rat hippocampus. PMID- 7874518 TI - Release of slow axonally transported proteins from the rat vagus nerve in vitro. AB - The cultured rat vagus nerve was used to investigate the release of [35S]methionine-labelled slow axonally transported proteins during regeneration. After metabolic labelling the released proteins were collected from an isolated compartment at the distal end of the nerve. Several proteins were released at a time point consistent with the arrival of slow axonally transported proteins at the collection compartment, including actin and a group of 150 kDa proteins. PMID- 7874519 TI - Anoxia induces an increase in intracellular sodium in rat central neurons in vitro. AB - Following our previous observations that anoxia induces a drop in extracellular Na+ in the brain slice and that removal of extracellular Na+ prevents the anoxia induced morphological changes in dissociated hippocampal neurons, we hypothesized that intracellular Na+ increases during anoxia in isolated neurons. Using the fluorophore Sodium Green in freshly dissociated rat CA1 neurons, and SBFI in cultured cortical neurons, we found that 10 min of anoxia caused an increase in Nai+ in both types of cells, with a latency of about 2 min. In CA1 neurons, fluorescence increased by an average of 20.34% (n = 8). The mean baseline Nai+ level (determined using SBFI) was 25 +/- 2.5 mM, which increased to about an average of 52 +/- 3 mM after 3-4 min. These and our previous results strongly suggest that Na(+)-mediated events are involved in anoxia-induced nerve injury. PMID- 7874521 TI - Immunocytochemical localization of the high molecular weight protease in brain. AB - Polyclonal antiserum against a high molecular weight glycosylated protease, purified from calf brain cytosol, was raised in rabbit and purified by immunoaffinity. The antibody specifically immunoreacted with the M(r) = 165,000 and 155,000 polypeptides of the protease. Immunocytochemical localization data revealed that the protease is localized in the pyramidal neurons, granular and glial cells of the hippocampus. Microscopic analysis of the pyramidal neurons indicates that the protease is present in the cytoplasm and extends to the dendrite and axon. The nuclei of these neurons remain unstained. PMID- 7874520 TI - The effect of the volatile anesthetic isoflurane on Ca(2+)-dependent glutamate release from rat cerebral cortex. AB - A major effect of volatile anesthetics is to reduce excitatory synaptic transmission. In the present study the stimulated release of glutamate under the influence of increasing concentrations of isoflurane was studied in vitro by utilizing hippocampal slices from Wistar rats. Ca(2+)-dependent release was calculated by subtracting stimulated release with blocked synaptic transmission (50 mM K+, 0 mM Ca2+ and 4 mM Mg2+) from total evoked release (50 mM K+, 2 mM Ca2+ and 1 mM Mg2+). Isoflurane 0.5, 1.5 and 3% reduced Ca(2+)-dependent release of glutamate to 69, 58 and 49%, respectively (P < 0.05 for all related to control). These results are in agreement with the possibility of reduced release of transmitter as a mechanism of action of volatile anesthetics. PMID- 7874522 TI - Collateral axonal projections from ventrolateral medullary non-catecholaminergic neurons to central nucleus of the amygdala. AB - Retrograde tract-tracing techniques were used to investigate whether catecholaminergic neurons in the ventrolateral medulla (VLM) send collateral axonal projections to both central nuclei of the amygdala (ACe) in the rat. Rhodamine-labelled latex microspheres or fluorogold (2%) were microinjected into the region of either the right or left ACe. After a survival period of 10-12 days, the rats were sacrificed and transverse sections of the brainstem were processed immunohistochemically for the identification of cell bodies containing the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH) or phenylethanolamine-N-methyltransferase (PNMT). Neuronal perikarya containing the retrogradely transported tracers were observed throughout the rostrocaudal extent of VLM, bilaterally. Approximately 10% of the retrogradely labelled neurons were observed to contain both retrograde tracers. The majority (79 +/- 6.8%) of these double labelled neurons were located within the caudal VLM and their number decreased rostrally. In addition, the proportion of double labelled neurons to single labelled neurons in VLM decreased rostrally; approximately 11% in the caudal VLM and 6% in the rostral VLM. Furthermore, approximately 21% of all VLM neurons that projected to ACe were found to be catecholaminergic: 75% of these were immunoreactive to TH and 25% to PNMT. However, no neurons were found in VLM that contained both retrograde tracers and immunoreactivity to TH or PNMT. These data demonstrate that axons originating from non-catecholaminergic neurons in VLM bifurcate to innervate ACe bilaterally. Although the function of these VLM neurons that project to both ACe is not known, they may be the anatomical substrate by which VLM neurons relay simultaneously autonomic and/or visceral sensory information to influence the activity of ACe. PMID- 7874523 TI - Stimulus intensity and the comparative efficacy of mu- and kappa-opioid agonists on nociceptive spinal reflexes in the rat. AB - The influence of stimulus intensity was tested on the relative spinal efficacy of intravenously administered mu- (fentanyl) and kappa-opioid (U-50,488) agonists. Spinal reflexes were generated by different intensities of noxious electrical stimuli in alpha-chloralose anaesthetized, spinalized rats. Both drugs became less effective as the intensity of C-fibre generated responses was increased, but U-50,488 retained the ability to reduce responses to the same degree as fentanyl. The effects were naloxone reversible. The results indicate that kappa-opioid receptor activation has similar potential for spinal analgesia as does activation of mu-opioid receptors. PMID- 7874524 TI - Postnatal care: teamwork in the community. AB - To offer continuity of care as recommended by Changing Childbirth, close communication between midwives and health visitors is important. Selective postnatal visiting allows continuation of visits after the tenth day and encourages communication between the midwife and health visitor. Good communication between a midwife and health visitor can ensure that a framework of care is provided to support mothers as they develop self-confidence and independence. To ensure continuity of care, midwives should involve health visitors during the antenatal period wherever possible. Formal and informal lines of communication between midwives and health visitors should be encouraged. PMID- 7874525 TI - Back care in pregnancy. AB - Early in pregnancy it is useful to encourage the mother to do some gentle exercise to offset some of the mechanical strain that will arise with postural changes. Manipulation of the lumbar spine and pelvic joints is possible until the sixth month for primigravidae and the fourth or fifth month for multiparae. The joints and soft tissues will respond very readily to gentle stretching techniques because of hormonal changes. It is appropriate for midwives to have a good working knowledge of the mechanical advantages and disadvantages of different maternal positions adopted during labour. PMID- 7874526 TI - Pre-eclampsia I: the midwife and detection. AB - Midwives must be alert to the possibility of pre-eclampsia by: Taking accurate and detailed genetic histories. Taking consistent blood pressure measurements. Testing urine for protein at every visit. Observing generalised oedema. Advising clients that headaches and epigastric pain should not be ignored. Fetal monitoring for intrauterine growth retardation. PMID- 7874527 TI - Keeping phenylketonuria under control. AB - The treatment of phenylketonuria (PKU) is one of the great success stories of modern medicine. It is likely that midwives will increasingly have more contact with women having PKU or giving birth to an infant with the condition. It is therefore important to have a good understanding of all aspects of PKU. Midwives can offer valuable support to parents whose children are found to have PKU. Maternal PKU is a major consideration as the benefits of screening in one generation may be lost in the next unless preventive treatment is appropriately implemented. PKU is one of the few conditions where effective screening and treatment can be measured. PMID- 7874529 TI - Inside an American nurse-midwifery unit. PMID- 7874528 TI - Phenylketonuria--a personal view. PMID- 7874530 TI - All change for educational funding? PMID- 7874531 TI - Learning to cope with stillbirth. PMID- 7874532 TI - Medication and the midwife: statutory control. PMID- 7874533 TI - My dream of autonomy. PMID- 7874534 TI - Support the supporters. PMID- 7874535 TI - Running training alters fiber type composition in spinal muscles. AB - The issue of whether exercise can induce changes in muscle fiber types has been long debated. Knowledge about the alterations in spinal muscle fiber types is scarce. In this study, the alterations initiated by long-distance running on spinal muscle fiber type distribution was studied. Ten young dogs were run on a treadmill for 55 weeks, 5 days a week, and ten dogs from the same litters served as controls. The daily running distance was gradually increased to 40 km and maintained at that level for the final 15 weeks. Histological sections were prepared from the cervical, thoracic, and lumbar multifidus muscles and the medial and lateral heads of triceps brachii and analyzed for the fiber type composition and cross-sectional area of fibers. In the lumbar multifidus, the numerical percentage of the muscle fibers with low oxidative capacity (type II) increased significantly in the running group. However, in the thoracic and cervical spine multifidus, the response to running resembled more of the significant shift from type II to type I fibers (with high oxidative capacity), which was also observed in the triceps brachii muscle. In these muscles, the quantitative image analysis of nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) reaction also demonstrated a shift towards a higher oxidative capacity within the type II fibers. The results show that training can induce changes in fiber type composition not only in limb muscles but also in the stabilizing spinal muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874536 TI - Epidemiologic study of low back pain in 1398 Swiss conscripts between 1985 and 1992. AB - The two objectives of this study, based on a sample of 1398 Swiss army conscripts born in 1966 who participated in a first study in 1985, were to measure the prevalence of low back pain (LBP) at age 26 years and its incidence between 19 and 26 years and to analyze the relationship between LBP and occupational, nonoccupational, or physical risk factors. The lifetime prevalence of LBP at age 26 was 69.1% and the incidence of LBP between 19 and 26, 44.7%. A history of LBP or a pathological physical examination result at age 19 did not predict the prevalence or the incidence at age 26. Standing, twisting, vibration, and heavy work were significantly associated with chronic LBP and/or the 1-year prevalence of LBP at age 26 (P < 0.05). The evolution of sport and leisure-time activities from age 19 to 26 did not differ between people with or without LBP. The ergonomic organization of the workplace should represent a major element of future strategies to prevent LBP. PMID- 7874537 TI - Aetiology, diagnosis and treatment of low back pain. AB - A total of 274 patients complaining of low back pain following injury was reviewed. Impact injuries were associated with soft-tissue strain, which was seen less often after twisting injuries. Twisting injuries were associated with disc prolapse more often than falls. Discogenic pain followed lifting injuries more often than jerking injuries. Slipping and jerking injuries were associated with poor outcomes, but the diagnosis was of no prognostic significance. The response to treatment was markedly influenced by the presence of a compensation claim. Only educational classes could be shown to have a significant effect on outcome. PMID- 7874538 TI - Delayed pain response after lumbar discography. AB - The delayed onset of symptomatic pain following lumbar discography (with no immediate pain response) is described in six patients, five with a minimum 2-year follow-up. It is usually seen in patients with nearly normal disc morphology who have incomplete or discrete annular tears that are not filled at the time of injection. Later (2-12 h in this study), dye leakage occurs through these lesions, thereby precipitating the discogenic pain. This phenomenon may be missed and is probably more common than previously believed due to early discharge from the hospital, the patient expecting discomfort after the invasive study (hence no complaint is made), and the clinician being unaware of this delayed symptom, thereby not asking about it in follow-up. Close patient questioning regarding a delayed onset of symptomatic pain after discography is, therefore, an essential element in diagnostic information following this study. PMID- 7874539 TI - Anterior lumbar fusion using a hybrid interbody graft. A preliminary radiographic report. AB - This is a radiographic report of 40 patients (20 men, 20 women) who underwent anterior lumbar interbody fusions (73 levels) utilizing a "hybrid" interbody graft composed of femoral cortical allograft (FCA) bone and iliac crest cancellous autograft bone. The average age at surgery was 38 years (range 17-64 years), and follow-up averaged 1.4 years (range 1.0-2.4 years). Nineteen of the patients had undergone previous lumbar surgery. Thirty-two patients (63 levels) underwent anterior fusion combined with some type of posterior fixation, and eight patients (10 levels) had no posterior fixation. Types of posterior fixation included: for 20 patients (36 levels) Steffee variable screw placement fixation, for 10 patients (23 levels) translaminar facet screws (TFS), for 1 patient (3 levels) Knodt rods and for 1 patient (1 level) facet screws. Based on the persistence of lucent lines at the graft-host interface, three patients (one level each) were felt to have non-unions at their latest follow-ups at 1.4, 1.5 and 2.0 years, respectively. Two of these patients had no posterior fixation, and the other had TFS fixation. The overall fusion rate was 96% (70 of 73 levels). The fusion rate for all levels treated with posterior fixation was 98% compared with 75% for those without fixation. Intervertebral disc heights (IVDH) were measured on all films and corrected for magnification with computer assistance. On average, the IVDH was increased postoperatively but returned to preoperative values at follow-up. IVDH loss was independent of the type of instrumentation used. No complications arose from the use of the hybrid graft.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874540 TI - Reconstruction of an iliac crest defect with a bioactive ceramic prosthesis. AB - Between June 1987 and December 1990, an iliac crest prosthesis made of bioactive apatite- and wollastonite-containing glass ceramic (A-W.GC) was used in 60 patients for the reconstruction of the iliac crest defect after harvesting autogenous tricortical iliac bone graft. The clinical results of this prosthesis were satisfactory. No patients felt spontaneous pain in the reconstructed area, and 93% of the patients had no tenderness there. In the radiological evaluation at the final follow-up, no apparent "radiolucent clear zone" was detected at the prosthesis-iliac bone junction in 98% of the patients. Excellent new bone formation between the prosthesis and the iliac crest was also noticed in 96% of the patients. The A-W.GC iliac crest prosthesis was beneficial for reconstruction of the iliac crest defect. PMID- 7874541 TI - Fixation of thoracolumbar fractures with the Dick fixator: the influence of transpedicular bone grafting. AB - Fifty patients with thoracolumbar fractures were treated by internal fixation using the Dick fixator. In the first 22 patients (group 1) this was accompanied by posterior intertransverse grafting. The technique was then modified in the following 28 patients (group 2) to include transpedicular elevation of the depressed vertebral end plate and grafting of the vertebral body, in an attempt to reduce the postoperative loss of correction of the kyphotic deformity. The clinical records and X-rays were reviewed to determine whether the change in technique had achieved this objective and whether it affected operative time, blood loss, postoperative recovery and complications. The mean operating time and blood loss in group 1 were 2 h, 38 min and 650 ml, respectively, and in group 2 2 h, 59 min and 783 ml. These differences were not statistically significant. Time from operation to mobilisation and discharge from hospital were related to neurological deficit, but there was no significant difference between group 1 and group 2 in this regard. There was no difference in the complication rate between the two groups and no complication attributable to transpedicular bone grafting. The radiological results postoperatively and at a mean follow-up period of 9 months were assessed by measurement of the kyphosis angle, anterior vertebral height, anterior displacement, scoliosis, and reduction in cross-sectional area of the spinal canal. In group 1 the mean preoperative kyphosis angle and anterior vertebral height were 8 degrees and 21 mm; postoperatively these values were -12 degrees (lordosis) and 27 mm; and at follow-up they were -4 degrees and 24 mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874542 TI - Posterior stabilization of C2 metastases by combination of atlantoaxial screw fixation and hook plate. AB - A new technique for the stabilization of metastatic cervical instability of the axis and/or neighboring vertebrae at lower levels is described. By a combination of the transarticular screw fixation C1/2 (Magerl) with the hook plate technique (Magerl) (or facultatively with a 1/3 tubular or 3.5 mm dynamic compression plate) from a posterior approach, the risks and stresses on the patient of a transoral or a combined extended technique are avoided, creating a proven biomechanically stable situation. The new technique is particularly helpful in those patients with a rapid progression of their malignant disease in whom local tumor growth is not expected to compress the spinal cord, and palliative stabilization of the unstable upper cervical spine can avoid neurological deficits or alleviate pain syndromes at a minimized morbidity due to surgery. The new technique has been successfully applied in a limited clinical series of four patients with metastasis of the cervical spine, resulting in substantial improvement of the general condition and cervical pain syndrome and stability of the assemblage during the observation period (4-9 months). PMID- 7874543 TI - Cervical hyperostosis: a rare cause of dysphagia. Case description and bibliographical survey. AB - Dysphagia can be caused by disorders of the cervical spine. Very seldomly, prominent osteophytes of the ventral spine are responsible. The case of a 63-year old patient with large anterior osteophytes from C3 to C7 is presented. The successful ablation of these spondylophytes relieved the patient of his swallowing difficulties. Up to now there have been many different opinions about the etiology of this disease. In this special case, a diffuse idiopathic skeletal hyperostosis, also known as Forestier's disease or diffuse idiopathic skeletal hyperostosis, seems to be the most likely cause. PMID- 7874544 TI - Degeneration model of the porcine lumbar motion segment: effects of various intradiscal procedures. AB - In an experimental study with 18 minipigs, we have tried to establish a model for the standardized evaluation of mechanical, histological and radiological phenomena of degenerative and reparative processes within the lumbar motion segment. Comparing different operative techniques revealed that the intradiscal application of hyaluronic acid into the nuclear defect is likely to enhance the regeneration process. Using the measurement of disc compliance, a semiautomatic picture analyzer and a new semiquantitative disc score could make future studies more comparable. From this basis, the intradiscal application of hyaluronic acid deserves further evaluation. PMID- 7874545 TI - Results of the AO spinal internal fixator in the surgical treatment of thoracolumbar burst fractures. AB - The potential for clinical instability following thoracolumbar fractures has evoked a progressive increase in interest in the surgical treatment of unstable thoracolumbar fractures. From September 1988 to October 1991, 44 thoracolumbar burst fractures were treated surgically by the AO Spinal Internal Fixator at the Orthopaedics and Traumatology Clinics of Ankara Social Security Hospital. Mean follow-up period was 28.8 (range 12-48) months. Fourteen (31.8%) of the patients were female, and 30 (68.2%) were male. Postoperatively, the mean anterior vertebral height loss and spinal canal compromise were corrected by 36.5% and 39.9%, respectively. Also, postoperatively 15.9% of improvement was obtained in the mean kyphosis angle. The mean compression angle, which was 19.5 degrees preoperatively, was corrected by 12.3 degrees and came to an average of 7.1 degrees postoperatively. In light of these data, it is suggested that the AO Spinal Internal Fixator effectively restores three-dimensional alignment of the spine and provides a rigid fixation. PMID- 7874546 TI - Elevated cerebrospinal fluid proteins in sciatica caused by disc herniation. AB - We carried out a study of cerebrospinal fluid (CSF) proteins in 180 patients with sciatica caused by lumbar disc herniation to elucidate further the degree and mechanisms of protein elevations. The 63 controls were patients with tension headache or migraine without aura. The CSF/serum albumin ratios were higher in the patients (mean 8.84, SD 5.16) than in the controls (mean 5.60, SD 2.33). Similar differences were found for the CSF/serum IgG ratios and the CSF-total proteins. The CSF/serum albumin ratios, CSF/serum IgG ratios and the CSF-total protein concentrations were higher in men than in women among the patients. We suggest that the significant difference in ratio parameters between patients and controls indicates a leak of plasma albumin, most likely IgG, into the CSF in patients with sciatica. The leak was more pronounced in men. Also in the control group the CSF/serum albumin and CSF/serum IgG ratios were higher in men. PMID- 7874547 TI - Spontaneous fracture of the sternum in a child being treated in a Boston brace for kyphoscoliosis. A case report and review of the literature. AB - We report a child who suffered from short stature of unknown aetiology and rigid thoracolumbar kyphoscoliosis and developed a symptomatic spontaneous fracture of the sternum while being treated in a Boston brace. Modification of the brace was followed by uneventful healing of the sternal fracture. To our knowledge no mention has been previously made of this extremely rare complication, but the spine surgeon who treats complex spinal deformities in early childhood with braces should be aware of this potential complication, particularly if they are associated with rigid rotational kyphosis. PMID- 7874548 TI - A lumbar chordoma treated with a wide resection. AB - Chordomas are rare skeletal tumors arising from the embryonic remains of the notochord [18, 30]. These tumors tend to appear in midline regions, particularly at the upper and lower extremities of the spinal column. We report the case of a 74-year-old woman with radicular compression associated with an L3 chordoma that was treated with a wide resection. PMID- 7874549 TI - Iliolumbar hernia following bone grafting. AB - A 40-year-old man developed a lumbar hernia through an iliac bone graft donor site. The defect was repaired using an autologous bone graft reinforced by titanium mesh. PMID- 7874550 TI - Combined anterior and posterior convex epiphysiodesis for progressive congenital scoliosis in children aged < or = 5 years. AB - Six patients aged < or = 5 years with congenital scoliosis due to vertebral malformation were treated by anterior and posterior epiphysiodesis of the convexity. In all cases the pattern of deformity was a kyphoscoliosis. The average age at operation was 3 years 6 months, average follow-up was 4 years 6 months, and average preoperative angles were 42 degrees in the frontal and 36 degrees in the sagittal plane. The fusion included the malformative zone and the superior and inferior adjacent vertebrae. Two patients had a fusion effect, three patients had a true epiphysiodesis effect, and one patient had a postoperative progression of the deformity. Epiphysiodesis of the convexity is a treatment proper for the growing period, allowing the child either to reach skeletal maturity without needing further treatment or to achieve an adequate torso height to finish the treatment with a classical vertebral arthrodesis. PMID- 7874551 TI - Results of anterior discectomy without fusion for treatment of cervical radiculopathy and myelopathy. AB - In this retrospective study 180 patients were submitted to anterior discectomy without fusion for cervical radiculopathy and myelopathy. Ninety-five patients presented with single-level discopathy, the main symptom being radiculopathy in this group. Eighty-five patients presented with multiple-level discopathy, the main symptom being myelopathy instead of radiculopathy. No serious complications were observed in either group. In the single-level discopathy group the improvement of the radiculopathy was 94.7% and of the myelopathy, 87.5%, whereas in the multiple-level discopathy group the improvement of the myelopathy was 57.1% and of the radiculopathy, 66.6%. It is concluded that anterior cervical discectomy without interbody fusion is a safe and effective surgical method for the treatment of radiculopathy and less so for myelopathy. PMID- 7874552 TI - Progressive cord compression secondary to thoracic disc lesions in Scheuermann's kyphosis managed by posterolateral decompression, interbody fusion and pedicular fixation. A new approach to management of a rare clinical entity. AB - During a brief period of 21 months (November 1988 to August 1990) the neurospinal unit of our institution registered three cases of Scheuermann's kyphosis with herniation of the thoracic discs. Local and intercostal pain, progressive spasticity with gait disturbance and urinary hesitancy were the most common presenting symptoms. All of the patients were surgically managed by posterolateral decompression, interbody fusion (posterolateral approach) and pedicular screw plate fixation. The average length of follow-up was 25 months. Results were excellent in two patients and good in one. All patients had improvement in neurological status, were pain-free and demonstrated sound fusion within 5 months. A new approach to management of this rare clinical entity is documented. PMID- 7874553 TI - Prognostic factors in anterior decompression for metastatic cord compression. An analysis of results. AB - During the 10-year period 1981-1990, 59 patients suffering from spinal cord or cauda equina compression underwent anterior spinal decompression and in most cases spinal restabilization with methylmethacrylate cement and/or instrumentation. Follow-up in 55 patients showed that 75% were improved neurologically by the procedure, one-third of these showing complete recovery from the spinal cord compression. The results in younger female patients suffering from metastatic breast cancer were considerably better than those of older men with prostatic metastases. Other genitourinary system tumors also had a relatively poorer prognosis. There was a significantly better result for metastatic lesions of the thoracic or thoracolumbar spine than for lesions in the lumbar spine causing cauda equina paralysis. PMID- 7874554 TI - Surgery of cervical spine metastases: a retrospective study. AB - Fifty-one consecutive patients with metastatic lesions of the cervical spine were treated surgically. The most common primary tumor types were breast cancer and myeloma. In 14 (27%) patients, the cervical lesion was the first manifestation of the malignancy. All patients suffered from severe pain but only six had long tract symptoms. Five tetraparetic patients were confined to bed. Vertebral body collapse occurred in 73% of cases. The surgical technique was individualized according to the patient's general condition, the site of metastasis on the vertebra, and the level and number of levels bearing in mind that the treatment is palliative in nature. The goal of treatment was a better quality of life. In the upper cervical spine the technique described by Sjostrom et al. was used, if technically possible. If the odontoid process had been totally destroyed, an occipitocervical stabilization was chosen. In the lower cervical spine, an anterior approach was used to resect the tumor growth. Anterior support was provided with bone cement if the patient was not expected to survive long; otherwise bone grafting was used. In cases with two or more levels of involvement, a combined anteroposterior stabilization was usually performed. Good pain relief was achieved postoperatively. The operation was generally well tolerated by the patients, mild dysphagia being the most common complaint. One patient died 2 days postoperatively of heart failure, giving a postoperative mortality of 2%. Rhizopathy symptoms were relieved totally in 15 patients and partially in 6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874555 TI - Influence of geometrical factors on the behavior of lumbar spine segments: a finite element analysis. AB - The main objective of this study was the assessment of the influence of geometrical factors on the behavior of lumbar segments. To this end, a three dimensional, parameterized, finite element model of the lumbar spine was used, and the results were compared with inhouse experimental results and with the few published experimental results available concerning either the geometry of the tested samples or the differences observed at different vertebral levels. Furthermore, in order to appreciate the relative importance of the geometry, the influence of the variation of some other parameters was studied, such as the orientation of the facet joints, the gap between the articular processes, and the Young's modulus of the disk fibers. As a first approach, a series of computations was carried out in order to evaluate the role of geometry in the mechanical behavior differences observed at different levels. It has been found that geometrical factors do exert a noticeable influence on the behavior of the spine, especially those which interfere with the dimensions of the intervertebral disk. PMID- 7874556 TI - A universal spine tester for in vitro experiments with muscle force simulation. AB - We report a new apparatus to determine the quasistatic, three-dimensional, load displacement characteristics of spines including muscle forces. The loading frame can be adapted to mono- and polysegmental specimens from the lumbar or cervical spine as well as to entire spines. Three force and three moment components can be applied in either direction individually or in combination with no constraint on the resulting motion; the loads can be applied at user-chosen rates of application and release with continuous recording of displacements, so as to study either creep or relaxation. The loads and displacement-measuring devices are computer-controlled. Thus, this testing device provides a tool for many kinds of stability tests and for basic research of spine biomechanics. A first experiment shows that the application of muscle forces significantly affects the load-deformation characteristics and intradiscal pressure. PMID- 7874557 TI - The value of functional computed tomography in the evaluation of soft-tissue injury in the upper cervical spine. AB - A functional rotatory computed tomography (CT) study of 423 whiplash patients with cervical spine soft-tissue injury was undertaken to determine its diagnostic value. The results are correlated with previous CT studies on normal subjects, and an evaluation of paradox motion, in which the lower vertebra rotates more than the vertebra immediately superior to it, is given. Asymmetrical left/right rotation reached the pathological value in 36% of the patient population at the level of C0-1. Twice as many patients had hypermobile rotation to the left as compared with the right, perhaps indicating that the right alar ligament is more often damaged in injuries involving the whiplash mechanism. A higher percentage of pathological values for hypermobile rotation was found at the level of C0-1 than at C1-2. Patients exhibiting paradox rotation had a significantly higher amount of rotation to the contralateral side than did those who exhibited no paradox rotation. These findings validate the use of functional rotatory CT in the evaluation of soft-tissue damage of the upper cervical spine resulting from whiplash injury. PMID- 7874558 TI - Pectoralis major transfer for winging of the scapula. AB - From November 1988 to July 1992 eight patients with painful, chronic, disabling winging of the scapula caused by isolated serratus anterior paralysis had pectoralis major muscle transfer extended by a fascia lata graft. Six men and two women were treated. Duration of symptoms ranged from 12 to 35 months. Seven patients had a positive result on electromyography. In addition, four patients had multidirectional instability of the shoulder on the side of the winging. The postoperative follow-up period ranged from 12 to 57 months (average 27.1 months). Excellent results were obtained in all patients. In addition, patients with associated multidirectional instability improved, and only one subsequently required additional shoulder surgery. The described method of coiling and suturing the donor graft is believed to account for the consistent results and absence of substantial complications. Pectoralis major muscle transfer extended by a fascia lata graft appears to be an excellent operation for correcting scapular winging. PMID- 7874559 TI - A comparison of double-plate fixation methods for complex distal humerus fractures. AB - A modified method of fracture fixation of complex distal humeral fractures with medial and lateral plates and bolts was biomechanically tested and compared with previously described fixation techniques. Compressive stiffness coefficients were determined for three classes of fixation before and after fatigue cycling. This procedure was followed with compressive loading to failure. The results show that in the most unstable fracture type tested this new fixation method provides increased strength and stability. Early clinical follow-up examinations of patients treated with this technique show that this method is a reasonable fixation alternative for the complex distal humerus intercondylar fracture. PMID- 7874560 TI - Three-dimensional corrective osteotomy for treatment of cubitus varus after supracondylar fracture of the humerus in children. AB - Cubitus varus deformity after supracondylar fracture of the humerus in children generally includes deformities of varus, hyperextension, and internal rotation. Presently almost all corrective osteotomies for treatment of cubitus varus deformity have been limited to correction of only the varus or of the varus and hyperextension deformity. Electromyographic study and stick picture motion analysis have revealed unphysiological joint motion and muscle activity around the joint in elbows with cubitus varus, hyperextension, and internal rotation deformity. On this basis we have successfully attempted simultaneous correction of all three deformities. The end results in 41 elbows have been satisfactory. In conclusion, we recommend simultaneous correction of the three elements of cubitus varus deformity to restore anatomic alignment of the elbow joint. PMID- 7874561 TI - Internal rotation deformity and tardy ulnar nerve palsy after supracondylar humeral fracture. AB - Internal rotation deformity may contribute to the onset of tardy ulnar nerve palsy after a supracondylar fracture. We measured the angle of deformity in five patients with nerve palsy using an electrogoniometer and compared it with that of patients without palsy. Varus deformity of patients with nerve palsy was 23 degrees +/- 15.2 degrees (mean +/- SD), and that of patients without palsy was 12 degrees +/- 10.9 degrees. No significant difference was seen between the two groups. Internal rotation deformity of patients with nerve palsy was 16 degrees +/- 4.2 degrees, and that of patients without palsy was 2.5 degrees +/- 6.3 degrees (p < 0.05). The results suggest that internal rotation deformity contributes to the development of tardy ulnar nerve palsy. PMID- 7874562 TI - Pathogenesis and treatment of cubital tunnel syndrome caused by osteoarthrosis of the elbow joint. AB - We consider the primary cause of cubital tunnel syndrome caused by osteoarthrosis of the elbow joint to be degenerative osteophytes originating in the humeroulnar joint underneath the ulnar nerve. In the operative procedure the ulnar nerve in the cubital tunnel is fully exposed by cutting the soft tissues covering the nerve, because some of the soft tissues often seem to compress the nerve. Internal neurolysis is performed with microscopy in cases where the constriction is severe. Osteophytes in the humeroulnar joint underneath the nerve are removed. The osteophytes and loose bodies in the anterior and the posterior parts of the joint are also removed to increase joint motion. In 75 of 77 cases recovery of the ulnar nerve palsy and improvement in the range of joint motion were obtained. PMID- 7874563 TI - Surgical resection of the distal clavicle. AB - Distal clavicle resection is frequently performed for persistent acromioclavicular pain. However, patient outcome after this procedure has not been well described. The results of subjective and objective retrospective analysis of 23 open distal clavicle resections in 21 patients are reported. Patients were evaluated with a questionnaire, roentgenographs, physical examination, and isokinetic muscle strength testing at an average of 30 months after surgery. Eighteen of 23 shoulders had good or excellent postoperative ratings. All patients had normal motion. No significant weakness of the operated shoulder was seen on objective muscle testing when compared with the unoperated shoulder. The average preoperative Hospital for Special Surgery score was 34, and the average postoperative score was 84. Age and hand dominance were unrelated to postoperative outcomes. Less predictable results were obtained in patients with workmen's compensation and in those patients involved in litigation. Open distal clavicle resection yields good to excellent results in properly selected patients and does not create significant subjective or objective weakness. PMID- 7874564 TI - Arthroscopic resection of the distal clavicle with a superior approach. AB - Forty-one patients (41 shoulders) with acromioclavicular joint disease refractory to conservative treatment underwent arthroscopic distal clavicle resection. Thirty-one men and 10 women with an average age of 32 years were studied. The dominant extremity was involved in 68% of the patients. At an average follow-up period of 31 months (range 24 to 49 months), 18 excellent, 16 good, and seven poor results were found. Twenty-seven (93%) of 29 shoulders with acromioclavicular arthritis or osteolysis of the distal clavicle went on to have satisfactory results compared with only seven (58%) of 12 shoulders with previous grade II acromioclavicular separations or acromioclavicular hypermobility. Total amount of bone removal did not correlate with success, if the resection was even. Five reoperations were done; one uneven resection was revised with arthroscopy, and four shoulders underwent acromioclavicular stabilization procedures. The high failure rate in patients with even subtle acromioclavicular instability (42%) suggests that in these cases formal stabilization with ligament reconstruction should be considered in addition to resection of the distal clavicle. PMID- 7874565 TI - The terrible triad: anterior dislocation of the shoulder associated with rupture of the rotator cuff and injury to the brachial plexus. PMID- 7874566 TI - Multidirectional instability: current concepts. AB - Multidirectional instability (MDI) of the shoulder is a complex problem that is not yet well understood. Instability in several directions is termed MDI, but the precise definition, classification, cause, and optimal method of treatment remains elusive. The cause appears to be multifactorial, with biochemical and biomechanical abnormalities present in shoulders with MDI. The biomechanical factors responsible for preventing MDI include bony architecture, concavity compression from the deepening of the glenoid by the labrum, stability from the ligaments, primarily the inferior glenohumeral ligament complex and the superior capsular structures, and muscular control by use of force couples, especially stabilization of the scapula. Current recommended treatment is initially nonoperative, with aggressive physical therapy aimed at strengthening the rotator cuff and the scapular stabilizers. Patients who fail to respond to a nonoperative regimen often improve with surgical stabilization, which is usually an inferior capsular shift or a variant of that procedure. After this surgery immobilization of the operated shoulder for 6 to 8 weeks is recommended by most authors. PMID- 7874567 TI - Medical genetic study of eight pancreatic cancer-prone families. PMID- 7874569 TI - Phase II clinical trial of carboplatin, ifosfamide, with oral mesna for metastatic breast carcinoma. AB - Twenty-five women with advanced breast carcinoma refractory to first-line chemotherapy entered a phase II trial to evaluate the efficacy of ifosfamide and carboplatin. Additionally the trial assessed the clinical usefulness of oral 2 mercaptoethane sulfonate (mesna) for urothelial protection. Two partial remissions were observed (8%); toxicity was significant but acceptable, with no treatment-related deaths. The combination of ifosfamide and carboplatin had little activity as the second-line treatment in our population of patients with heavily pretreated metastatic breast cancer. Oral mesna was effective for urothelial protection, permitting outpatient administration of ifosfamide. PMID- 7874568 TI - Phase II evaluation of methotrexate, vinblastine, doxorubicin, and cisplatin (M VAC) in advanced, measurable breast carcinoma. AB - The purpose of this study was to determine whether methotrexate, vinblastine, doxorubicin, and cisplatin, each individually active in metastatic breast cancer (MBC), could, in combination, produce an overall response rate, median survival, and long-term survival sufficiently promising to merit its consideration for phase III trials in MBC and as induction therapy prior to autologous bone marrow transplant. From July 1986 through February 1990, 30 patients with stage IV, measurable breast carcinoma received M-VAC: methotrexate--30 mg/m2 days 1, 15, 22; vinblastine--3 mg/m2 days 2, 15, 22; doxorubicin--30 mg/m2 day 2; cisplatin- 70 mg/m2 day 2. Cycles were repeated at 4-week intervals for up to six courses. Median age was 53 years (range 34-64 years). Prior treatment included adjuvant cyclophosphamide, methotrexate, and 5-Fluorouracil in 12 patients, radiotherapy in 13 patients, and hormonal therapy in 14 patients. Eleven patients were ER (+) at the time of initial diagnosis. Five patients had disease restricted to bone and/or nodes; the other 25 had visceral-dominant sites of metastases, with or without bone involvement, or evidence of rapid, inflammatory chest wall relapse. Twenty-nine of 30 patients were evaluable for toxicity and response; all were evaluable for survival. The major overall response rate was 83%, with a 21% complete remission rate. The chief toxicity was bone marrow suppression, with grade 4 granulocytopenia in 20 patients, grade 3 in 7 patients, and grade 3 and 4 thrombocytopenia in 5 patients. Grade 3 stomatitis occurred in 9 patients. Renal insufficiency was clinically insignificant, and neurotoxicity mild, with 7 patients sustaining grade 1 or 2 paresthesias. Median time to progression was 9 months and median survival 19 months (range, 5-84+ months) with 4 patients still alive at least 45+ months or more from the start of treatment and 2 presently free of progressive disease. Although highly toxic, M-VAC produces a response rate and survival duration in visceral-dominant MBC competitive with, if not superior to, conventional regimens such as CAF (Cytoxan, doxorubicin, 5 fluorouracil); it therefore merits further investigation in conjunction with hematopoietic growth factors and as cytoreductive therapy prior to autologous bone marrow transplantation. PMID- 7874570 TI - Regression of skin recurrences of breast carcinomas treated with intralesional injections of natural interferons alpha and gamma. AB - Two groups of patients with disseminated breast carcinomas who had failed radiotherapy, chemotherapy, and hormonotherapy were treated with natural interferon alpha (nIFN-alpha) alone or in combination with nIFN-gamma delivered in cycles of 10-12 intralesional (i.l.) injections to recurrent and metastatic lesions. In group, I, 16 skin lesions in 12 patients received nIFN-alpha alone resulting in 7 complete regressions verified histologically (CR), 7 partial regressions (PR), and no regressions (NR) in 2. Group II included 4 patients in whom 7 cutaneous recurrences were treated with nIFN-alpha/nIFN-gamma (5 CR, 2 PR), 2 were injected with nIFN-alpha alone (1 CR, 1 PR), and 1 received nIFN gamma alone (PR). Two additional patients in group II were given i.l. injections of nIFN-alpha/nIFN-gamma to lymph node metastases (1 CR, 1 PR). Clinical toxicity was experienced by 5 of 12 patients in group I and by all the patients in group II and was controlled in most instances by antipyretics. Systemic antitumor effects were not appreciable clinically. Nevertheless, noninjected lesions exposed only to systemic levels of IFNs, when studied immunohistochemically, displayed an immunological response similar to that of IFN-injected lesions, although less intense. Therefore, IFNs can be useful in controlling locoregional recurrences of breast cancer even in patients who are not responding to other forms of therapy. Furthermore, in addition to the local antitumor actions, they appear to be capable of eliciting systemic immunological effects. PMID- 7874571 TI - Correlation of TGF-beta 1 expression with medroxyprogesterone acetate responsiveness in mouse mammary adenocarcinomas. AB - We investigated the expression of transforming growth factors beta 1 and alpha (TGF-beta 1, TGF-alpha) in hormone-responsive (MPA-R) and unresponsive (MPA-U) tumor lines obtained from medroxyprogesterone acetate (MPA)-induced mammary adenocarcinomas in BALB/c mice. The tumors were transplanted into MPA-treated and untreated mice. TGF-beta 1 gene expression was observed in the MPA-R lines growing in untreated animals, but not in MPA-treated mice. TGF-beta 1 mRNA was not detected in the MPA-U tumor lines growing in either MPA-treated or untreated animals. In MPA-R lines the levels of TGF-beta 1 expression were inversely correlated to growth rate. High-affinity TGF-beta 1 receptors were present in the MPA-R tumors. These results suggest that one of the mechanisms by which MPA exerts its proliferative effect on MPA-R tumor lines is inhibition of the expression of TGF-beta 1. Thus, the lack of expression of TGF-beta 1 in MPA-U tumors may be related to the acquisition of autonomous growth. PMID- 7874572 TI - Role of calcium in the regulation of ornithine decarboxylase enzyme activity in mouse colon cancer cells. AB - Activity of ornithine decarboxylase (ODC), one of the rate-limiting enzymes in the pathway of polyamine biosynthesis, is regulated by various factors. In this study, we examined the role of Ca2+ in the regulation of ODC enzyme activity in mouse colon cancer cells (MC-26). KCl, a membrane-depolarizing agent that opens the voltage-dependent Ca(2+)-channel to increase intracellular Ca2+, decreased serum-induced ODC enzyme activity in MC-26 cells in a dose-dependent, reversible fashion. Both verapamil and nifedipine, inhibitors of the L-type voltage dependent Ca(2+)-channel, decreased serum-induced ODC enzyme activity. W-7, a calmodulin inhibitor, decreased ODC enzyme activity in a dose-dependent, reversible fashion while trifluoperazine, another calmodulin inhibitor, failed to affect ODC enzyme activity in MC-26 cells. Our findings indicate that intracellular Ca2+ participates in the regulatory mechanism of ODC enzyme activity in MC-26 cells, although the exact role of Ca2+ is still unclear. PMID- 7874573 TI - Arterial thrombosis associated with granulocyte-macrophage colony-stimulating factor (GM-CSF) administration in breast cancer patients treated with dose intensive chemotherapy: a report of two cases. AB - The occurrence of arterial thrombosis reported in other breast cancer series has largely been confined to the upper extremities, ipsilateral to a previous mastectomy site and clinically manifest as cerebral vascular accidents. This case report describes 2 patients who experienced iliac artery thrombosis temporally related to receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) and dose-intensive chemotherapy for metastatic breast cancer. A review of the literature concerning arterial thrombosis as relevant to breast cancer treatment and GM-CSF is included. PMID- 7874574 TI - Considerations for the use of cytokine-secreting tumor cell preparations for cancer treatment. AB - Limited efficacy of chemotherapy in most solid tumors has revived interest in immunotherapeutic approaches for cancer. One novel form of immunotherapy is the use of cancer vaccines consisting of tumor cells genetically engineered to secrete cytokines. The rationale for this immunization strategy is based on the existence of tumor-specific antigens, on the importance of the cellular arm of the immune system in mediating an effective antitumor response, and on the role of cytokines in regulating the cellular immune response. Such tumor vaccines showed considerable promise in various animal models and induced potent antitumor immunity in the host, which led to regression of established tumors and, moreover, produced immunological memory protecting animals from a subsequent tumor challenge at a distant site. Translated to the human patient, this implies that genetically modified tumor vaccines may be able to eradicate or reduce existing tumor deposits to subclinical levels as well as provide long-term protection from regrowth of tumor cells. This report will review and discuss the concept and rationale for the use of cytokine-secreting tumor vaccines for the treatment of human malignancies. PMID- 7874575 TI - Infusional cancer chemotherapy: historical evolution and future development at the Cancer Center of Boston. AB - Clinical studies of infusional chemotherapy at The Cancer Center of Boston began in 1980 at the New England Deaconess Hospital and from 1986 to the present have continued under the auspices of a network of free-standing ambulatory cancer treatment centers in Massachusetts. Over 50 peer-reviewed articles on infusional chemotherapy and 3 textbooks on the topic have been published by clinical investigators associated with The Center, including phase I, II, and III trials, multidrug infusion programs, and combined chemo/radiotherapy programs. Bringing together the total experience in this review provides a perspective to address those areas that have been inadequately explored and a framework for future development in the field. This paper represents a comprehensive synthesis and analysis of clinical infusional studies carried out at The Center to the present with the goal of achieving those objectives. PMID- 7874576 TI - CA 72-4 serum marker--a new tool in the management of carcinoma patients. AB - Among the new tumor markers that have been recently proposed, CA 72-4 is of particular interest, not only for its capabilities in diagnosing and monitoring certain neoplastic diseases, but also for its excellent specificity. Several studies focused on the potential clinical usefulness of CA 72-4 in gastrointestinal (GI) and gynecological cancer, showing a sensitivity of approximately 40% in colorectal and gastric cancer and 50% in ovarian cancer, with an overall specificity of more than 95%. Longitudinal evaluations of patients with either GI or gynecological malignant diseases demonstrated that significant elevations of CA 72-4 serum levels may be predictive of recurrent disease. Moreover, the combination of CA 72-4 with other known serum markers, such as CEA and CA 19-9 for GI cancer or CA 125 for ovarian cancer, indicated that an increase in the sensitivity can be achieved without substantial changes in the overall specificity, improving the possibility of monitoring these patients. In conclusion, these results provide a strong argument for the use of CA 72-4 in the management of these neoplastic diseases. PMID- 7874577 TI - Mt. Carmel House: a home for terminally ill patients who cannot go home. PMID- 7874578 TI - Introduction to imaging brain tumor metabolism with positron emission tomography (PET). AB - The need for prompt and detailed evaluation of cancers and their treatment is requiring increasingly sophisticated methodologies for in vivo assessment. Morphological detail as provided by CT and MRI has yielded significant advances in diagnostic medicine. In spite of such advances, the means of achieving the clinical goals of improved quality and quantity of life in many cancer patients remain elusive. It is becoming increasingly evident that only with the addition of complementary physiological and biochemical data will further advances occur. While neither in vivo morphological imaging with CT or MRI nor physiological imaging with PET or MRS can provide the resolution of microscopic or cellular level assessment, all can provide macroscopic or regional data. With PET, however, exploration of the kinetics or chemical processes occurring at the cellular level is providing a "biological resolution" not heretofore achieved with in vivo imaging. Application of this complementary morphological and biochemical diagnostic information will likely lead to significant advances in patient management in the immediate future, most of which would probably not be achievable using any individual technique. Efficacy studies should be performed, however, when introducing any new high-technology methodology into clinical practice. A number of retrospective and prospective trials on PET applications in clinical oncology are ongoing sponsored by organizations such as the Institute for Clinical PET and the Western PET Association. Detailed studies also are underway to estimate the "cost" of delivery of PET services to the community (146). Numerous PET feasibility studies in animal models have demonstrated that no one radiotracer serves as the best agent for tumor imaging in all cases. Such studies with radiolabeled amino acids, sugars, and nucleoside derivatives, representatives of the major classes of biomolecules, have demonstrated variable tumor uptake dependent on such parameters as the type of cancer, organ of origin, animal host, and chemical structure of the radioligand. Detailed analysis of tracer uptake using multiple ligands in a variety of animal tumor models and clinical patients suggests that while given types of cancers may be better imaged with certain radiotracers, the use of multitracer imaging provides the specific details necessary for appropriate interpretation of tumor status. In addition, in cases where the diagnosis is uncertain, such information could have a significant impact on patient management by reducing the diagnostic differential. In spite of the many successes achieved with FDG in brain tumor imaging, the most well-known example of the problems that can arise with PET image interpretation is with the use of this agent.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7874579 TI - Mt. Carmel hospice care for terminally ill patients. PMID- 7874580 TI - Birds as animal models for the comparative biology of aging: a prospectus. AB - Bird species are dramatically longer-lived than similar-sized mammals, in spite of two traits--high metabolic rate and elevated blood glucose--which some modern theories of aging suggest should be associated with accelerated senescence. As a consequence of their longevity, birds may possess specialized protective mechanisms against free radical and Maillard reaction damage, and may offer insight into medical interventions for retarding aging. In this review we have highlighted a number of bird species which are commercially available, easily maintained, and more thoroughly characterized with respect to basic physiology than many biogerontologists realize. There seem to us to be few intrinsic barriers to the development of several avian "mice"--extensively characterized species exhibiting exceptionally long life and retarded aging--and for these to become readily accessible as a laboratory resource for the gerontological research community. PMID- 7874581 TI - Effects of dietary restriction on the change in aortic alpha 1-adrenoceptor mediated responses during aging in Fischer 344 rats. AB - These studies examine changes in alpha 1-adrenoceptor-stimulated contraction, accumulation of inositol phosphates (IPs) and calcium influx during aging, and the effect of dietary restriction. The potency of norepinephrine (NE) at stimulating aortic contraction was highest in aortas from 1-month-old rats compared to 6- or 24-month-old rats, while the potency at stimulating IP accumulation was higher in 6- and 24-month-old rats. The fact that the NE potency for IP accumulation is not decreased with age and is even increased a little, indicates that PI hydrolysis is not limiting for contraction. The data from 24 month-old dietary restricted rats support the same idea. Dietary restriction greatly increased the potency of NE for IP accumulation in the old animals (by 20 fold), but did not restore potency for contraction. Nifedipine (1 microM), a calcium channel blocker, inhibited the NE-stimulated aortic contractile response by 28% in 1-month, 40% in 6-month, and 67% in 24-month-old rats. While nifedipine did not inhibit NE-stimulated IP accumulation in 1-month-old aortas, it inhibited by 30% in 6-month-old aortas and by 27% in 24-month-old aortas. Dietary restriction (DR) did influence the inhibitory effects of nifedipine. Nifedipine inhibition of NE-stimulated contraction in 24-month-old DR rats was comparable to the inhibition in 6-month-old ad libitum (ad lib) controls and was less than in 24-month-old controls. Furthermore, nifedipine was less effective at inhibiting NE-stimulated IP accumulation in aortas from 24-month-old DR rats compared to 24 month-old controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874582 TI - Anti-tumor action of dietary restriction is lesion-dependent in male Fischer 344 rats. AB - The effects of dietary restriction (DR) on spontaneous oncogenesis in male Fischer 344 rats were analyzed. Previously reported analyses of studies carried out in our laboratory demonstrated that DR reduces the incidence and delays the onset, but not the progression, of leukemia in male F344 rats. In this report, the influence of DR on pituitary tumors, adrenal pheochromocytoma, pancreatic islet cell tumors, and interstitial cell tumors of the testis was analyzed. DR reduced the relative incidence (relative onset rates) and delayed the onset of the four tumors. DR also retarded the progression (duration from onset to death) of pituitary tumors and pheochromocytoma. DR has delayed the onset of all tumors of the male F344 rat so far analyzed, but its effect on tumor progression appears to be lesion-dependent. PMID- 7874583 TI - Hyperadrenocorticism, attenuated inflammation, and the life-prolonging action of food restriction in mice. AB - Food restriction (FR), which extends life span, is associated with an enhanced diurnal elevation of glucocorticoids. This increase in glucocorticoids may contribute to longevity by chronically enhancing the same protective mechanisms mobilized during acute stress. The objective of this study was to determine if attenuation of inflammation, a presumably protective effect of glucocorticoids, occurs in FR mice. Two-month-old male BALB/c mice were either fed ad lib (AL) or FR (60% AL calories) for 2 months. After one month, the diurnal elevation of plasma corticosterone was threefold higher in FR mice. Two weeks after corticosterone sampling, a hind foot pad of each mouse was injected with 20 microliters of 4% carrageenan. Maximum observed edema did not differ between FR and AL groups, but edema was reduced at onset and fell earlier in FR mice. Results indicate that at least one inflammatory reaction is attenuated by FR and are consistent with the hypothesis that FR enhances a potentially protective glucocorticoid activity. PMID- 7874584 TI - Adrenocortical hyporesponsiveness and glucocorticoid feedback resistance in old male brown Norway rats. AB - This study was designed to examine adrenocortical function in old (30 months) and young (6 months) male Brown Norway rats. The following observations were made. First, stress induced a higher pituitary adrenocorticotropic hormone (ACTH) response in the aged male Brown Norway rats than in young rats, while peak circulating corticosterone (CORT) levels were not different. Moreover, this type of "repeated" stress involving subcutaneous injection and blood sampling at various time points by pinching the tail vein, evoked a prolonged ACTH and CORT response in the aged animal. Second, exogenous ACTH1-24 administered to dexamethasone-pretreated Brown Norway rats, used as an in vivo challenge test for adrenocortical function, resulted in a delayed CORT response in the aged rats. The termination of the CORT response to ACTH, however, was not different between young and old rats. Third, ACTH1-24 stimulation of adrenocortical cells in vitro showed a tendency to a reduced CORT output, when these cells were obtained from old animals. Fourth, adrenalectomy (ADX) differentially affected pituitary ACTH release at both ages. The initial post-ADX ACTH surge was more pronounced in the aged animals. Beyond 4 days post-ADX the old Brown Norway rats did not show the pronounced afternoon peak in circulating ACTH as was observed in the young animals. This study demonstrates that during the aging process a deficiency in adrenocortical function develops in the male Brown Norway rat. This deficiency involves a less efficient stress-induced activation of adrenocortical output of CORT having enhanced pituitary ACTH release as one of the consequences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874585 TI - Effects of chlordiazepoxide and scopolamine, but not aging, on the detection and identification of conditional visual stimuli. AB - Our previous studies revealed impairments in the ability of aged rats to detect brief, rarely and unpredictably occurring stimuli. The failure of these impairments to interact with the effects of benzodiazepine receptor (BZR) ligands was attributed to low demands on stimulus-related information processing. Thus, in the present experiment, rats of different ages were trained to detect visual stimuli that were flashing at 20 Hz, or were constantly illuminated, for 8, 3, or 5 sec. Additionally, selection of the correct lever to report detection required the processing of propositional rules (e.g., flashing-go left; constant-go right), i.e., the identification of the stimulus. All measures of performance varied with stimulus duration. Subsedative doses of the BZR agonist chlordiazepoxide (CDP; 3.13, 4.69 mg/kg), similar to the effects of the muscarinic antagonist scopolamine (.025, 0.1 mg/kg), impaired response accuracy, increased the number of errors of omission and decreased response latencies. Animals aged 28 months omitted more trials following the administration of CDP than 12-month-old rats. Age did not produce main effects and did not interact with the effects of the drugs on response accuracy. It is speculated that, as stimuli had to be presented for relatively long periods of time (to maintain above chance-level discrimination performance), demands on detection remained too low to replicate previously documented effects of age. The demonstration of interactions between the effects of age and of BZR-ligands appears to depend on combined demands for stimulus detection and identification. PMID- 7874586 TI - Long-term resistance training in the elderly: effects on dynamic strength, exercise capacity, muscle, and bone. AB - We examined the effects of 42 weeks of progressive weight-lifting training on dynamic muscle strength, peak power output in cycle ergometry, symptom limited endurance during progressive treadmill walking and stair climbing, knee extensor cross-sectional areas, and bone mineral density and content in healthy males and females aged 60-80 years, currently enrolled in a 2-year resistance training program. Subjects were randomized into either exercise (EX) or control (CON) groups (60-70 years: 38 males and 36 females; 70-80 years: 25 males and 43 females). EX trained several muscle groups twice per week for 42 weeks at intensities ranging from 50-80% of the load that they could lift once only (1 RM); CON did usual daily activities. After the 10 months there was no change in 1 RM strength in CON, but significant gains (mean increases up to 65%) in EX (no independent age or gender effects); 30% and 47% of the increase in 1 RM had occurred by 6 and 12 weeks, respectively. In EX, the 7.1% increase in peak cycling power output was significantly greater than in CON (+1.1%). The 17.8% improvement in symptom limited treadmill walking endurance was also greater than in CON (+3.4%), but the difference between groups during stair climbing was not significant (EX + 57%, CON + 33%). The cross-sectional areas of the knee extensors increased significantly by 5.5% in EX but were unchanged in CON. There were no changes in bone mineral density or content in either group. We conclude that long-term resistance training in older people is feasible and results in increases in dynamic muscle strength, muscle size, and functional capacity. PMID- 7874587 TI - Episodic memory and visuospatial ability in detecting and staging dementia in a community-based sample of very old adults. AB - BACKGROUND: This study examined the efficacy of a cognitive test battery in detecting and staging dementia in a community-based sample of very old adults. METHOD: The sample consisted of 398 nondemented and 108 demented adults taken from all the inhabitants in the Kungsholmen parish of Stockholm, Sweden (2,368 individuals), aged 75 years and older, who were part of a large-scale epidemiological study on aging and dementia. Participants received a cognitive test battery that consisted of specialized episodic memory tasks, as well as standardized psychometric measures of visuospatial ability and primary memory. RESULTS: A discriminant analysis revealed that highly supported episodic memory tasks (recognition, cued recall) were primarily responsible for correctly classifying normal old adults (94.5%) from those with the diagnosis of dementia (66.7%). Using the Mini-Mental State Exam (MMSE) as the criterion of dementia severity, a correct classification of 88.9% was achieved for mildly demented subjects and 77.8% for moderately demented subjects. Visuospatial tasks made the greatest contribution in distinguishing those at different levels of dementia severity. CONCLUSION: The results of this investigation indicate that cognitively supported measures assessing episodic memory may be particularly useful in the detection of dementia, whereas visuospatial measures are more effective in staging the disease. Consistent with biological models of the progression of dementia, this suggests that visuospatial abilities may deteriorate later and/or at a slower rate than episodic memory skills in the early stages of dementia. It is noteworthy that these conclusions are based on samples of very old adults taken from the general population. PMID- 7874588 TI - Influence of age and gender on skin vessel reactivity to endothelium-dependent and endothelium-independent vasodilators tested with iontophoresis and a laser Doppler perfusion imager. AB - BACKGROUND: The aim of this study was to evaluate the influence of age and gender on skin vessel reactivity to one endothelium-dependent vasodilator (acetylcholine, ACh), and two endothelium-independent vasodilators with different modes of action (nitroprusside and isoprenaline). METHODS: The substances were iontophoresed into the skin and the results were mapped through a newly developed laser Doppler perfusion imager. Thirty-four healthy, nonsmoking individuals without any medication and without atopic constitution participated in the study. The subjects, 13 men and 21 women, 18 to 80 years of age, were divided into subgroups according to age and gender. RESULTS: A correlation to age for the vascular responses to nitroprusside and, to a lesser extent, ACh was shown for the women (p = .0036 and .0920 respectively). Differences were also observed between the age and gender subgroups with respect to their response to these two substances: young and, to a lesser extent, middle-aged women differed from elderly women and middle-aged and elderly men. The response to isoprenaline was affected neither by age nor gender. CONCLUSIONS: The results of the study suggest that skin vessel reactivity to nitroprusside and, to a lesser extent, ACh is age dependent. This might reflect both functional and structural changes in skin vasculature with aging. Gender differences for these two substances are also suggested, with women exhibiting a greater increase in perfusion after iontophoresis than men. However, higher vasoconstrictor tone among the women may have influenced the results. PMID- 7874589 TI - Validation of the Minimum Data Set Cognitive Performance Scale: agreement with the Mini-Mental State Examination. AB - BACKGROUND: Almost all nursing homes in the United States are required by the 1987 Omnibus Budget Reconciliation Act to assess each resident's functional, medical, psychosocial, and cognitive status using a standard instrument known as the Minimum Data Set (MDS). We report a validation study to show that the MDS Cognitive Performance Scale (CPS), a cognitive measure generated from 5 MDS items (comatose status, decision making, short-term memory, making self understood, and eating) can be used to detect cognitive impairment as defined by the Mini-Mental State Examination (MMSE). METHODS: Two hundred subjects were randomly recruited from 8 nursing home facilities in North Carolina. Two medical students administered the MMSE, while a geriatric research nurse was responsible for collecting MDS cognitive items, which included the 5 items required for generating CPS scores. Cognitive impairment was defined by MMSE scores adjusted for education. Agreement between the CPS and the MMSE in identifying cognitively impaired subjects was then evaluated. RESULTS: The CPS showed substantial agreement with the MMSE in the identification of cognitive impairment; the sensitivity was .94 (95% confidence interval [CI]: .90, .98), the specificity was .94 (95% CI: .87, .96), and the diagnostic accuracy as measured by the area under the receiver operating characteristics (ROC) curve was .96 (95% CI: .88, 1.0). CONCLUSIONS: The MDS Cognitive Performance Scale, when performed by a trained research nurse using recommended protocols, provides a valid measure of cognitive status in nursing home residents. PMID- 7874590 TI - Enhanced hypothalamic-pituitary-adrenocortical axis responses to physostigmine in normal aging. AB - BACKGROUND: The purpose of this study was to determine the effects of normal human aging on the hypothalamic-pituitary-adrenocortical (HPA) axis response to the centrally active cholinesterase inhibitor physostigmine. This drug stimulates the HPA axis at a suprapituitary level by increasing central nervous system (CNS) cholinergic activity. METHODS: Plasma ACTH, beta-endorphin (beta E) and cortisol responses to a 10-minute infusion of physostigmine (.0125 mg/kg) were compared between groups of 10 normal older subjects (71 +/- 2 years [mean +/- SEM]) and 9 normal young subjects (27 +/- 2 years). Plasma physostigmine concentrations were measured to assess the comparability of the pharmacologic stimulus between groups. RESULTS: Endocrine responses were substantially greater in older subjects than young subjects for ACTH (p < .01), beta E (p < .01) and cortisol (p < .01). Plasma physostigmine concentrations did not differ between older and young subjects. CONCLUSION: This study demonstrated increased HPA axis responsivity to a CNS cholinergic stimulus in normal human aging. PMID- 7874591 TI - Health and functioning among the elderly of Marin County, California: a glimpse of the future. AB - BACKGROUND: The purpose of this study was to obtain information concerning the health status of the theoretically advantaged elderly population of Marin County, California, and to compare these data with those from other populations with different levels of socioeconomic status. METHODS: An age-stratified sample of 2,018 community-dwelling elderly residents of Marin was selected, and these participants were interviewed between 1989 and 1991. Interview items included medical history of life-threatening diseases and chronic conditions, reported and observed disabilities, and life-style characteristics. RESULTS: While the residents of Marin had lower mortality rates than the total U.S. population, there were few meaningful differences in measures of health and function in comparison to other elderly populations with substantially lower levels of socioeconomic status. The main exceptions were better memory performance and lower depressive symptomatology in Marin. Because of the many methodological differences, these comparisons must be viewed with caution. CONCLUSION: The general pattern of findings in this study indicates that while death has been postponed in this socioeconomically advantaged population, the prevalence of disease and disability has not. If true, this implies that residents of an affluent community can spend a longer rather than shorter period of their late life in a state of infirmity and in need of medical care. This appears to be especially true for women. PMID- 7874592 TI - Physical disability in older runners: prevalence, risk factors, and progression with age. AB - BACKGROUND: Concern exists that certain types of exercise, particularly vigorous activity, may increase physical disability among older individuals. We investigated the prevalence of, and risk factors for, physical disability in active older persons (runners), and examined factors influencing the progression of physical disability with age. METHODS: Physical disability, measured using the Health Assessment Questionnaire Disability Index, was assessed prospectively in 454 runners, age 50 or greater, over five to seven years by annual mailed questionnaires. Baseline sociodemographic, clinical, and life-style characteristics associated with the presence of any disability over the course of the study were determined and contrasted with those in 292 older non-runners who had been similarly followed. RESULTS: Two hundred twenty-two runners (49%) reported some physical disability during the study. The presence of arthritis symptoms at baseline was the most important risk factor for physical disability; older age, greater body mass index, strenuous work-related physical activity, and the use of more medications were also associated with a greater likelihood of physical disability. Among the non-runners, 224 (77%) reported some physical disability, and the presence of arthritis symptoms was also the most important risk factor for physical disability in this group. Age-related changes in physical disability differed between those with and without arthritis symptoms in both the runner and non-runner groups. CONCLUSIONS: The presence of arthritis symptoms was an important risk factor for physical disability among both older runners and non-runners, and also identified subgroups of individuals with different progressions of disability with age. PMID- 7874593 TI - Effect of age and pathology on left ventricular diastolic function: the diagnostic yield of Doppler echocardiography. AB - BACKGROUND: Doppler echocardiography has been proposed to detect left ventricular (LV) diastolic dysfunction in the elderly. However, the validity of this technique in differentiating the effects of pathology from those of normal aging has not been defined. METHODS: Doppler indices of LV diastolic function were obtained in 85 patients (34 hypertensive, 29 with coronary artery disease, 22 with both conditions) and in 56 healthy volunteers. RESULTS: A linear correlation with age was found for all parameters in controls, and for many parameters in patients. Also, in the presence of heart diseases, age exerted a powerful, independent effect on Doppler parameters. None of these differed between patients and controls in advanced age. CONCLUSION: Due to the prevailing age-related variations in Doppler indices of diastolic performance occurring beyond the age of 65, Doppler echocardiography cannot be employed to diagnose LV diastolic dysfunction in the elderly. PMID- 7874594 TI - Influence of autonomic blockade and aging on AV conduction and responses to verapamil in the beagle. AB - BACKGROUND: Age-related differences in responses to verapamil have been noted in both intact humans and isolated denervated perfused rat hearts. The study was designed to determine the effects of aging on intracardiac conduction and pharmacodynamic responses to verapamil, and also to determine the potential role of autonomic responses in previously reported age-related differences in responses to verapamil. METHODS: After stability of measures was demonstrated in senescent animals, nine young (aged 3-4 years: 12.3 +/- 2.4 kg; 5 female, four male) and nine senescent (aged 8-11 years: 12.0 +/- 2.2 kg; 5 female, four male) beagles were randomized to undergo 60-minute verapamil infusions during pentobarbital anesthesia alone or after 1 mg/kg propranolol and 0.5 mg/kg atropine. RESULTS: In the nonblocked state, verapamil increased A-A intervals (p < .001), P-R (p < .001), A-H intervals (p < .001), and AV Wenckebach block cycle length (p < .0001) and decreased blood pressure (p < .001) without age-related differences in responses. After autonomic blockade, heart rate and blood pressure decreased (p < .0001) and AV conduction intervals (p < .05) and AV Wenckebach block cycle length increased (p < .006). A-A intervals, A-H intervals, and AV Wenckebach block cycle length were significantly longer in senescent vs young beagles (559 +/- 87 vs 471 +/- 42 msec, p < .002; 103 +/- 6 vs 89 +/- 14, p < .05), 273 +/- 21 vs 238 +/- 26, p < .006, respectively). Verapamil effects on heart rate (p < .001) and AV conduction intervals (p < .007) and diastolic blood pressure (p < .003) were enhanced in younger, but not senescent, beagles after propranolol and atropine. DISCUSSION: Verapamil produced similar effects on heart rate, blood pressure, and AV conduction in young and senescent beagles during barbiturate anesthesia. After double pharmacologic autonomic blockade, heart rate and AV conduction intervals and AV Wenckebach cycle length were significantly longer in senescent beagles when compared to younger beagles. Responses to verapamil after pharmacologic double autonomic blockade were enhanced only in younger beagles, suggesting greater contribution of reflex responses to results during verapamil infusions in the nonblocked state in younger animals. PMID- 7874595 TI - A questionnaire to evaluate disability in osteoporotic patients with vertebral compression fractures. AB - BACKGROUND: Few studies have reported on the functional disability due to vertebral compression factors in osteoporosis. The Osteoporosis Functional Disability Questionnaire (OFDQ) was developed to assess disability in patients with osteoporosis and back pain due to vertebral fractures. The domains of the OFDQ include: quantitative indices of pain, a standard 20-item depression scale, 26 items relating to functional abilities, a scale of social activities, and confidence in the ability of prescribed osteoporosis treatment to reverse disability. METHODS: Reliability of the OFDQ was assessed using test-retest and internal consistency methods. Criterion validity was demonstrated by correlating disability against radiographic evidence of vertebral fractures. Construct validity was demonstrated through comparisons of 81 patients with osteoporosis and fractures to 37 healthy age-matched controls. Additional evidence was found in comparing 45 of the 81 cases who were actively engaged in an exercise program with 36 cases who were sedentary. RESULTS: The test-retest reliabilities ranged from .76 to .93, with internal consistencies from .57 to .96. The OFDQ correlated significantly with relevant spinal pathology, and showed significant improvements in activities of daily living and socialization when active exercisers were compared to inactive patients with osteoporosis. CONCLUSIONS: The OFDQ is a reliable instrument which correlates well with objective measures of osteoporotic spinal damage. It is also sensitive to changes in disability brought about by participation in our aerobic exercise program. The OFDQ may be a useful adjunct to measuring outcomes in other osteoporotic treatment protocols. PMID- 7874596 TI - Benzodiazepine use as a cause of cognitive impairment in elderly hospital inpatients. AB - BACKGROUND: Benzodiazepine drugs are used very frequently by the elderly and have been associated with a number of untoward events in them. In an earlier publication, we showed that there was an association between benzodiazepine use and episodes of confusion in hospital. The purpose of this study was to examine that association in more detail by studying only patients with intact cognitive function on admission and by taking into consideration a range of demographic, drug use, and clinical confounders. METHODS: A prospective cohort study was carried out of inpatients who had normal cognitive function on admission to hospital. The subjects were 418 hospital inpatients who had a normal result of a Mini-Mental State Examination (MMSE) performed within 24 hours of admission. They were aged 59-88 years. A clinical history and detailed drug use history were taken on admission and then the patients were followed prospectively for 10 days or until discharge, whichever was sooner. The MMSE was repeated every 2 days and all significant clinical events and episodes of delirium noted. RESULTS: 10.8% (95% Confidence Interval [CI]: 7.8-13.8%) of patients developed cognitive impairment (as indicated by a decrease in the MMSE). Factors that were statistically significantly related to the development of cognitive impairment included admission diagnoses of cancer or central nervous system (CNS) disease, alcohol consumption > 40 gms/day, hypoxia, and presence of benzodiazepines in the urine on admission. After adjusting for age, alcohol consumption, and admission diagnoses, those who reported taking benzodiazepines in daily doses equivalent to 5 mg or more of diazepam were at significantly higher risk of cognitive impairment than those who had not taken benzodiazepines (adjusted odds ratio = 3.5; 95% CI: 1.4-8.8). Twenty-one (5.0%, 95% CI: 2.9-7.1%) patients developed delirium as defined by the DSM-IIIR criteria. Age and hypoxia were statistically significantly related to the development of delirium. Due to the small number of cases of delirium, the power of the study to detect significant associations was low. CONCLUSIONS: Elderly hospital inpatients who have intact cognitive function on admission to hospital have a low risk of developing cognitive impairment and delirium during their hospital stay. In this population, however, benzodiazepine use accounted for 29% of cases of cognitive impairment which did occur. The data also suggest that dehydration, urinary retention, and an admission diagnosis of CNS disease may be important risk factors for delirium. PMID- 7874597 TI - Glucocorticoids and IgE: an in vitro paradox. PMID- 7874598 TI - Mechanisms of epithelial damage: are there parallels between bullous skin diseases and asthma? PMID- 7874599 TI - Epidemiology of hymenoptera allergy. PMID- 7874600 TI - Mast cell/fibroblast interactions. PMID- 7874601 TI - In vitro and in vivo effect of glucocorticoids on IgE and IgG subclass secretion. AB - Hydrocortisone (HC) as well as its synthetic derivatives have been shown to strongly enhance interleukin-4 (IL-4)-induced in vitro IgE synthesis. To investigate possible effects on IgG subclasses, peripheral blood mononuclear cells (PBMC) were incubated with different glucocorticosteroids in the absence or presence of IL-4. The glucocorticoids alone led to a strongly enhanced secretion of IgG1, IgG2 and IgG3, but not IgG4. The addition of IL-4 induced marked increases in IgG1 and IgG4, no changes in IgG3, but a consistent decrease in IgG2 synthesis. In order to find out whether these profound in vitro effects of corticosteroids are also reflected by changes in antibody serum levels during steroid treatment, 10 healthy volunteers took 25 mg prednisone for 7 consecutive days. We could not observe any significant changes of IgE or IgG subclass serum levels during or after this period. However, cell cultures performed after the glucocorticoid treatment revealed a marked decrease in the ability to produce IgG4 and a significantly lower potential to produce IgE in response to IL-4 alone or IL-4 and HC. We conclude that, although strongly implicated by the in vitro results, glucocorticosteroid treatment does not result in an increased allergy risk. PMID- 7874602 TI - Comparison of the levels of the major allergens Der p I and Der p II in standardized extracts of the house dust mite, Dermatophagoides pteronyssinus. AB - Allergy to the house dust mite Dermatophagoides pteronyssinus is mediated by IgE to the major allergens Der p I and Der p II in the majority of mite-allergic patients. In recent years, standardized preparations of D. pteronyssinus, commercially available from several sources, have become widely used for the diagnosis and immunotherapy of mite allergy. As standardization implies uniformity of allergen composition and potency, we directly compared the absolute and relative quantities of Der p I and Der p II in six different commercial standardized extracts of D. pteronyssinus. Our findings reveal variability in levels of both Der p I and Der p II, producing ratios of Der p I/Der p II ranging from 1.1/1 to 6/1. Although the content of minor allergens in the extracts was not evaluated here, their contribution to the overall reactivity of mite-allergic patients to the commercial extracts was judged to be minimal. This was demonstrated by showing that plasma depleted of reactivity to both Der p I and Der p II had virtually no residual IgE directed against extract components. The variation in the proportion of Der p I and Der p II among different D. pteronyssinus extracts is likely to influence their biological effectiveness. Patients with reactivity against only Der p I or Der p II, who were found to comprise approximately one-third of the mite-allergic population, may not respond optimally to extracts containing relatively low levels of the allergen to which they are sensitive. PMID- 7874603 TI - Ipratropium bromide nasal spray in non-allergic rhinitis: efficacy, nasal cytological response and patient evaluation on quality of life. AB - Intranasal fluorocarbon anticholinergic agents have been used to treat the nasal hypersecretion of perennial non-allergic rhinitis, but chronic use has been restricted either due to the potential for systemic anticholinergic adverse events or due to the irritating properties of the fluorocarbon metered dose formulations. This study evaluates a new aqueous nasal formulation of ipratropium bromide (Atrovent Nasal Spray 0.03%) in subjects with perennial non-allergic rhinitis in a double-blind, placebo-controlled trial. Two hundred and twenty eight patients were randomized to receive two sprays per nostril of either ipratropium bromide (42 micrograms/nostril) or placebo-administered three times a day as an aqueous nasal spray over an 8-week interval. Patients were evaluated bi weekly and maintained daily diaries for duration and severity of nasal symptoms. Ipratropium bromide reduced the mean severity and duration of rhinorrhoea within the first week and throughout the 8 weeks of active treatment compared with placebo (P < 0.05). Secondary endpoints of efficacy (patient and physician global assessments and a quality of life assessment) also supported the use of ipratropium bromide nasal spray for rhinitis symptom control. With the reduction in rhinorrhoea by the ipratropium bromide nasal spray, patients reported a marked improvement in daily moods vs placebo (P < 0.01). Both placebo and ipratropium bromide nasal spray induced a modest reduction of nasal congestion, sneezing and postnasal drip. This improvement in these other nasal symptoms was consistent with the known soothing effects of a nasal saline vehicle. There were no drug related serious or systemic anticholinergic adverse events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874604 TI - Identification of allergens from the mite Blomia tropicalis. AB - In some tropical areas the mite Blomia tropicalis is a clinically important allergenic component of house dust, inducing specific IgE immune response in patients with allergic respiratory diseases such as asthma and rhinitis. The identification of allergens of this mite is necessary to obtain appropriate reagents for diagnostic and treatment procedures. We carried out this study using immunoblotting to detect the allergens of B. tropicalis. Our results demonstrate that this mite has one major allergen (11-13 kDa) and three other important allergens with about 50% binding (64, 36 and 33 kDa). Therefore, B. tropicalis should be regarded as an important source of allergens in the house dust in tropical areas, besides those derived from other mites. PMID- 7874605 TI - House dust mite allergen (Der p I) and respiratory symptoms in children: a case control study. AB - The association between house dust mite allergen in house dust and childhood respiratory symptoms was investigated in a case-control study of 259 children with reported chronic respiratory symptoms and 257 control children without reported respiratory symptoms. The Der p I concentration in floor dust of the living room and bedroom and in mattress dust was determined using an enzyme immunoassay. Venous blood samples were taken from all children for serum IgE determination against house dust mite (Dermatophagoides pteronyssinus) by radioallergosorbent assay (RAST). A questionnaire was administered to the parents of the children to elicit information about the home, about changes made to the home in the past in relation to respiratory symptoms, and about a number of risk factors for childhood respiratory disease. In 83% of the dwellings of cases and 89% of those of controls, Der p I concentrations higher than 2000 ng/g were found, and in 54% of the dwellings of cases and 57% of those of controls, the concentrations exceeded 10,000 ng/g dust. In a crude analysis, cases were generally exposed to lower Der p I concentrations than controls. Restriction of the analysis to cases sensitized to dust mites, and non-sensitized controls, taking the type of floor covering into account, showed not significantly higher Der p I concentrations in bedroom floor dust of cases. However, restriction of the analysis to cases sensitized to dust mites and cases not sensitized to house dust mites--adjusting for allergen avoidance measures taken in the past--revealed a positive association between the Der p I concentrations in bedroom floor dust and mattress dust and sensitization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874606 TI - Measurement of airborne rat urinary allergen in an epidemiological study. AB - The suitability of radioallergosorbent test (RAST) inhibition to quantify occupational exposure to rat urinary aeroallergen (RUA) has been assessed. When using a constant pool of rat allergic sera, the reproducibility of the assay over 1 year was comparable to that reported for other immunoassays; at 50% RAST inhibition the inter-assay coefficient of variation (CV) was 7.0% and the intra assay CV was 3.0%. The assay was highly specific for rat urine; mouse urine was 1100-fold less potent at inhibiting the rat urine RAST system. Significant inter assay variation in the 'high' control was not due to batch variation and was relatively small when compared with the variation in RUA concentrations in the occupational environment. Measurement of workplace RUA exposure demonstrated that those directly involved in the care of rats experienced the highest RUA exposure of the nine occupational groups studied (animal technicians GM = 23.10 micrograms/m3), dead animals (e.g. post mortem GM = 1.60 micrograms/m3, scientists GM = 0.67 microgram/m3) and rat tissue (e.g. slide production GM = 0.04 microgram/m3). In view of the complexity of rat allergens, RAST inhibition is an appropriate method for the quantification of occupational exposure to rats. PMID- 7874607 TI - Pollen-related allergy in the European Mediterranean area. PMID- 7874608 TI - Pathological definition and evaluation of diabetic neuropathy and clinical correlations. AB - Diabetic neuropathy is a major complication of diabetes mellitus affecting to an equal extent type 1 and type 2 patients. Various mechanisms including metabolic and vascular abnormalities have been proposed to explain the progressive pathological changes that occur in peripheral nerve. Regardless of the precise mechanisms, structural abnormalities lead to functional changes which eventually result in the clinical manifestations of diabetic neuropathy. Possible interventions that may influence the progressive disease process include intensive insulin therapy and aldose reductase inhibitors. This article reviews the proposed pathogenetic mechanisms underlying diabetic neuropathy, their effects on nerve histomorphometric changes and ultrastructure typical of diabetic neuropathy, and potential therapeutic interventions and their impact on disease progression. PMID- 7874609 TI - End-stage complications of diabetic neuropathy: foot ulceration. AB - Diabetic polyneuropathy is a major complication of diabetes mellitus that frequently leads to foot ulceration. Because of economic impact of foot ulceration and subsequent amputation, major initiatives are under way in the United States and the United Kingdom to reduce their incidence by up to 50%. Although diabetic ulcers may have an ischemic and neuropathic component, the majority are neuropathic. Results from studies have shown a strong association between the neuropathy and the subsequent development of foot ulcers. However, other predisposing factors such as high foot pressures, inappropriate footwear, and other extrinsic pressure usually must be present, together with neuropathy, to cause foot ulcers. Therefore, the challenge to the physician is to identify the patient at risk and intervene so as to educate and prevent the occurrence of foot ulcers. PMID- 7874610 TI - Clinical testing in diabetic peripheral neuropathy. AB - Diabetic polyneuropathy is a complex disease of progressive nerve fiber loss. Initial screening and diagnosis in clinical practice usually depend on assessment of subjective complaints. A need exists for objective, simple, and reproducible assessment tools that can be readily used in clinical practice. The importance of early diagnosis is highlighted by the recent North American Diabetes Control and Complications Trial where intensive insulin therapy reduced the risk of developing diabetic neuropathy by 61%. At the University of Michigan, we have developed an outpatient neuropathy program. Patients are given a questionnaire and a brief screening examination, designated the Neuropathy Screening Instrument. Diabetic neuropathy is confirmed and staged in patients with a positive Neuropathy Screening Instrument, by a quantitative neurologic examination and nerve conduction studies, designated the Diabetic Neuropathy Score. The Michigan program has been compared with well-established instruments and has been found to be sensitive and reproducible for screening and diagnosis. We believe the program provides a valuable tool for the clinician in the practice setting and should allow diagnosis and intervention earlier in the course of diabetic neuropathy. PMID- 7874611 TI - Role of electrophysiological studies in diabetic neuropathy. AB - Electrophysiological studies are a reproducible and noninvasive method of assessing peripheral nerve function. The sensitivity of these methods has been validated in population-based and clinical studies, and the variability of test results is typically lower than with other noninvasive tests of nerve function. It has been recommended that standardized procedures including temperature control and equipment calibration be utilized with electrophysiological testing. The failure to detect significant changes in nerve conduction studies from clinical studies may be due to poor standardization of technique and inadequate sample size to detect differences. Baseline results from a multicenter, randomized trial indicate that different electrophysiological measures are highly correlated and reproducible. This and future studies that incorporate standardized techniques and an adequate sample size should be able to detect significant differences between treatments and identify effective therapeutic interventions for diabetic neuropathy. PMID- 7874612 TI - Planning care for neurology and neurosurgery patients with critical illnesses. PMID- 7874613 TI - Acute and chronic cerebral white matter damage in neonatal hydrocephalus. AB - The neonatal cat model of kaolin-induced hydrocephalus is associated with progressive and severe ventriculomegaly. In this experiment we studied the evolution of the histopathological changes in hydrocephalic (n = 23) cats from 5 168 days after the induction of hydrocephalus along with age-matched controls (n = 10). In the periventricular white matter, extracellular edema and axonal damage were present within days of the onset of hydrocephalus. This was followed by reactive gliosis, white matter atrophy, and in some animals gross cavitation of the white matter. Even in the chronic, apparently compensated state there was ongoing glial cell death. Six cats were shunted an average of 23.6 +/- 6.5 days after the induction of hydrocephalus because they were no longer able to feed independently. In spite of clinical improvement the white matter changes persisted. Overt cortical changes were minimal except where areas of white matter destruction encroached upon the deep layers. The white matter changes are very similar to those seen in periventricular leukomalacia and suggest that ischemia plays a role in neonatal brain injury caused by hydrocephalus. PMID- 7874614 TI - Proliferating cell nuclear antigen expression in the survival of astrocytoma patients. AB - The PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA), is known to show immunoreactivity in routinely processed paraffin embedded tissue. This antibody was applied to 72 astrocytic tumours from surgical biopsy material obtained in a ten year period. The PCNA labelling index (LI) obtained by image analysis was compared with patient's survival, age at diagnosis, and Karnofsky score as well as the histological grade of tumour. The survival analysis shows that patients with tumour PCNA LI of more than 6% have significantly poorer prognosis than those with 6% and below. In addition, there is also good correlation between PCNA LI with age, Karnofsky and tumour grade. This study suggests that although the PCNA expression of astrocytoma could be a useful predictor of patient's outcome, it is not an independent prognostic factor but has derived its statistical association with survival secondarily through its relationship with tumour grade, age and Karnofsky score. PMID- 7874615 TI - Frameless stereotaxy for pre-treatment planning and post-treatment evaluation of radiosurgery. AB - In our centre, 111 patients have been treated with linear accelerator stereotactic radiosurgery. Angiographic, CT and MRI images are generated and the target coordinates calculated in 3 dimensions. For CT scanning, cross sections of perpendicular and oblique fiducial markers are seen. For follow-up CT scans done without the frame, a virtual frame is generated by means of a computer program that places fiducial markers on each CT scan cut, as if the patient had been wearing the OBT frame and the scan produced with the gantry parallel to the base of the frame. The position of the oblique marker may be calculated by knowing the thickness and position of each CT cut. Various natural fiducial markers (bony landmarks) are identified by coordinates in the scan with the patient wearing the real frame and in the scan with the virtual frame applied. A transformation matrix is utilized to establish the equivalence between the original CT scan with the real frame applied and subsequent scans without the real frame but with the virtual frame applied. In effect, the virtual frame is re-applied in exactly the same position as the real frame. Lesion measurements may then be duplicated and growth or regression accurately established. The uncertainty in this system of re application residues in possible patient movement, CT scan slice thickness and inter-observer error in the identification of natural fiducial markers. PMID- 7874616 TI - Spinal somatosensory evoked potentials in patients with tethered cord syndrome. AB - We studied the electrophysiological changes occurring in six patients with tethered cord syndrome. Evidence of spinal malformations was provided by magnetic resonance imaging. The functional assessment of the spinal cord was performed by analysing both spinal and cortical somatosensory evoked potentials. The evoked electrospinogram was recorded from the thoracic and lumbosacral spinous processes. The N22 lumbosacral potential was selectively affected, being rostrocaudally displaced and reduced in amplitude or even absent in patients with neurological signs indicating a segmental lower cord lesion. Inter-peak somatosensory evoked potentials latency was normal in all cases, suggesting that ascending axonal potentials in the dorsal column fibres may be synchronized. Segmental potentials of the lumbosacral response, originating from the post synaptic activity of dorsal horn interneurons, are selectively affected in this syndrome resulting from the rostrocaudal displacement of the spinal cord due to tethering. Our findings in the clinical field are consistent with previous experimental evidence indicating a different sensitivity of the gray vs. white matter to progressive stretching. PMID- 7874617 TI - Progression and outcome of patients in a Canadian dementia clinic. AB - Five hundred and fifty-three patients were referred to a Canadian dementia clinic for standardized evaluation. The majority (83.5%) had a dementia with Alzheimer's disease (AD) accounting for 89% of dementias. Patients with probable AD who were followed for five years had variable rates of progression, increased mortality (37.1%, 2.5 times the expected rate) and a high rate of institutionalization (79%). Simple demographic (age) and social factors (marital status) were strong predictors for institutionalization. It was extremely difficult at presentation to predict the rate of progression. The prevalence of AD in autopsied cases was 62.5%. Clinic patients were younger, had milder dementias, and were more likely to have AD than patients identified in the course of a contemporaneous population based dementia prevalence study. PMID- 7874618 TI - [Medico-surgical treatment of Pott's disease. Our attitude in Gabon]. AB - Twenty-six of 95 adults treated for tuberculous spondylitis, between 1982 and 1993, underwent surgery. Twenty-one exhibited neurological deficits: radicular deficits: 4, and progressive spinal cord syndromes: 17 (incomplete, 13, complete, of acute onset: 4). Vertebral body compression fracture was the most prominent finding. Indications for surgery were neurologic: 11, mechanical: 1, etiologic: 1, and mixed: 13. Twelve patients had vertebrectomies, 3 laminotomies and 11 laminectomies. The average follow-up was 23 months. The neurological recovery was complete in 16 cases, partial in 4 cases and unchanged in one case. Bony consolidation occurred after 3-5 months. The medicosurgical treatment produced a very high cure rate, so rapidly, that it became the treatment of choice in our setting. Moreover, that allows to specify the diagnosis. Anterior decompression and fusion is recommended in the cervical and lumbar spine. In the thoracic segment, significant kyphosis is infrequent, so that surgical correction is rarely necessary. Laminotomy may occasionally be indicated for posterior decompression for abscess. Laminectomy is now preferred for uncommon cases of thoracolumbar posterior compression by tuberculous arachnoiditis or associated posterior vertebral tuberculosis. Indications for open biopsy are discussed. PMID- 7874619 TI - Iatrogenic false aneurysm following repair of intracranial aneurysm. AB - False aneurysm of the intracranial arteries occurs infrequently as a complication of head injury and rarely as a consequence of other pathology. A case of false aneurysm of the supraclinoid internal carotid artery following minor intraoperative injury during clipping of a basilar-superior cerebellar aneurysm by the pterional approach is described. False aneurysm is a potential cause of recurrent intracranial hemorrhage after successful aneurysm clipping. Arterial bleeding which appears to come from the region of a branch origin should be viewed with concern even if it subsides spontaneously. PMID- 7874620 TI - Unilateral Creutzfeldt-Jakob disease presenting as rapidly progressive aphasia. AB - A 64-year-old man presented with a three day history of progressive Broca's aphasia, followed within 3 weeks by exclusively right-sided myoclonus, rigidity, and dystonia. Within 4 weeks he was globally aphasic. He died within 7 weeks of onset. In the final week, rigidity and myoclonus became bilateral. CT and MRI were normal. SPECT showed diminished perfusion of the left hemisphere. EEG showed periodic discharges on the left. At autopsy, there were marked cortical spongiform change, neuronal loss, and gliosis throughout the left hemisphere and in the right occipital cortex. Elsewhere in the right hemisphere, spongiform change was non-existent to minimal. There was moderate spongiform change in the molecular layer of the cerebellar cortex, much more marked on the left. Clinical and pathological unilateral cerebral predominance extended to the ipsilateral cerebellum. Creutzfeldt-Jakob disease is an important consideration in patients with rapidly progressive unilateral cerebral signs associated with a movement disorder. PMID- 7874621 TI - Neuropsychological functioning in unilateral cerebellar damage. AB - A woman had a left superior cerebellar artery infarct associated with reduced hexamethylpropileneamine oxime uptake on SPECT scan of the basal ganglia and frontoparietal areas of the opposite hemisphere performed poorly in some neuropsychological tests indicating right hemisphere dysfunction. There was a lengthening of reaction and movement times with the hand ipsilateral to the lesion. These deficits were temporary. A unilateral cerebellar lesion can produce neuropsychological deficits, possibly because of hypoperfusion in contralateral frontoparietal regions, but spontaneous neuropsychological remissions may occur. PMID- 7874622 TI - Diagnosis of vascular dementia: Consortium of Canadian Centres for Clinical Cognitive Research concensus statement. AB - Interest in vascular causes for cognitive impairment is increasing, in recognition that such causes are common, and possibly preventable. This has led to attempts to better define vascular dementia and its natural history. Several sets of criteria for the diagnosis of vascular dementia have been proposed. We provide a brief overview of the background to the initiation of a Canadian consensus conference, established by the Consortium of Canadian Centres for Clinical Cognitive Research (C5R) and report the conclusions reached at that conference. To date, no one set of criteria is demonstrably superior to another; we have therefore not endorsed any of the competing sets, nor have we recommended our own. Instead we suggest that empiric studies are required to establish valid criteria. A diagnostic checklist, which combines existing criteria and additional data, is attached for clinicians wishing to participate in such studies. PMID- 7874623 TI - The role of hip arthroscopy in the diagnosis and treatment of hip disease. AB - OBJECTIVE: To report the results of arthroscopy performed on adults with hip disease who did not respond to extended conservative treatment and to evaluate the relationship between clinical findings, radiologic tests and surgical abnormalities. DESIGN: A case study. SETTING: New England Baptist Hospital, Boston, Mass. PATIENTS: Fifty-nine patients (32 women, 27 men) with refractory hip pain, between the ages of 17 and 69 years, who were seen between January 1989 and January 1992. INTERVENTION: Hip arthroscopy. MAIN OUTCOME MEASURES: Cause of hip pain, results of physical examination and operative findings. RESULTS: In 26 patients the cause of hip pain was traumatic; in 21 the cause was idiopathic. On physical had pain on straight leg examination, 56% of patients reported painful clicking of the hip joint, 37% had pain on straight leg raising, 9% had decreased extension and 34% had had episodes of locking of the joint. Five percent had pain predominantly in the thigh, 41% reported at least one episode of "giving way" of the hip and 7% had snapping of the iliotibial band. At arthroscopy, 69% of patients had synovitis in the hip joint, 59% had a tear of the acetabular labrum, 39% had loose bodies, 32% had degenerative arthritis and 27% had a chondral defect. On statistical analysis, significant (p < 0.05) relationships were found between acetabular labral tears and preoperative complaints of clicking or giving way, between loose bodies and preoperative locking and between degeneration of the hip joint and thigh pain. CONCLUSION: Arthroscopy of the hip is a valuable diagnostic and therapeutic procedure for patients with hip pain refractory to conservative therapy. PMID- 7874624 TI - Core decompression of the femoral head for avascular necrosis: indications and results. AB - OBJECTIVE: To evaluate the effectiveness and safety of core decompression in the treatment of avascular necrosis (AVN) of the femoral head. DESIGN: A case study. SETTING: The department of orthopedic surgery in a major university hospital. PATIENTS: All patients with AVN of the femoral head, stages I to IVA, were included regardless of the cause of the necrosis. Three hundred hips were available for analysis. The follow-up ranged from 2 to 12 years. INTERVENTION: Core decompression of the femoral head was performed with an 8-mm Michele trephine inserted from just below the greater trochanter into the centre of the necrotic lesion to within 5 mm of the articular surface. Two more trephine tracts were made with a 5-mm or 6-mm trephine. The normal portion of cancellous bone recovered from the intertrochanteric region was thinned with a rongeur and was placed loosely into the central decompression channel at the end of the procedure to serve as a graft. MAIN OUTCOME MEASURES: Anteroposterior and lateral radiographs, taken immediately before surgery and at the final follow-up, clinical hip evaluation according to the Harris scoring system, and the need for total hip replacement. RESULTS: One patient sustained a subcapital fracture 1 month after surgery due to a fall. There was one case of nonfatal pulmonary embolism, one case of pneumonia and one case of thrombophlebitis of the thigh. Forty-six percent of operatively managed hips showed no radiographic progression of disease compared with only 19% of nonoperatively managed hips. Thirty-five percent of the operatively managed hips required total hip replacement compared with 77% of nonoperatively managed hips. The results in hips with early (stages I and II) AVN were only slightly better than those of hips with advanced (stages III and IVA) disease. However, the results in hips with small areas of necrosis in both stages I and II were much better than those with larger lesions; only 7% of the former group required total hip replacement after decompression and cancellous bone grafting. CONCLUSIONS: Core decompression with cancellous bone grafting is a safe and effective procedure for the treatment of early AVN of the femoral head. Results with this form of treatment are considerably better than those obtained in patients treated nonoperatively. Decompression with or without bone grafting is the author's treatment of choice for patients with early AVN of the femoral head. PMID- 7874625 TI - Osteotomy of the pelvis for the management of hip disease in young adults. AB - Alternatives to total hip arthroplasty should always be considered for patients younger than 45 years. The indications for pelvic osteotomy are painful acetabular dysplasia with subluxation of the hip and early secondary degenerative arthritis, in which the majority of the deformity is on the acetabular side of the joint. For more severe deformity combined pelvic and femoral osteotomies may be necessary. Depending on the extent of the acetabular deformity there are a number of pelvic osteotomies available. With careful patient selection, correct indications and precise operative technique, significant relief of symptoms and excellent function may be obtained in most patients for 8 to 10 years after the operation. Pelvic osteotomy thus postpones the need for total hip arthroplasty to a stage in life at which results are better, and it enhances the bone stock to support the acetabular component. PMID- 7874626 TI - Femoral osteotomy for secondary arthritis of the hip in young adults. AB - Osteotomy around the hip is a valuable and important treatment option in hip disease. It may be used on either side of the joint or in a combined fashion. The authors review the scientific background to femoral osteotomy and summarize its role in the treatment of developmental dysplasia, nonunion of femoral neck fractures, osteonecrosis, slipped capital femoral epiphysis and Perthes disease. They conclude that it is a most useful tool for the contemporary hip surgeon. The procedure may not be appropriate for elderly patients with arthritic deterioration of the hip, but in carefully selected young adults with clearly defined antecedent developmental conditions, the results can be excellent and long lasting. Careful preoperative planning is emphasized; particular attention must be paid to the possibility of arthroplasty in the future because insertion of the stem of a hip prosthesis can be a problem difficult. PMID- 7874627 TI - Hip arthrodesis: an important option for advanced disease in the young adult. AB - Despite increasing confidence in the intermediate and long-term results of total hip replacement, considerable and justifiable concern remains about its use in young, active adults. Hip arthrodesis is a valuable, although unpopular, option in this group of patients. The authors describe, step by step, the standardized technique of arthrodesis that they first used in 1981, and they review the results of their experience. The importance of precise positioning of the fusion is emphasized: 20 degrees of flexion, 5 degrees of external rotation and neutral abduction-adduction. Intraoperative radiography to check the positioning is strongly advised. Because total hip arthroplasty will likely be necessary at a later date, every effort should be made to preserve the abductors, and the greater trochanter should be fixed in place at its normal level. If these precautions are taken and if the patient is carefully selected and properly educated preoperatively, a high success rate can be expected for hip arthrodesis. PMID- 7874628 TI - Choosing the socket in total hip arthroplasty. AB - Significant improvements have been made in the long-term results of cemented femoral components, but there has been little improvement in the results of cemented acetabular components. Polyethylene wear debris has been proposed as the most important factor causing loosening of cemented acetabular components. Polyethylene thickness and femoral-head size affect the rate of acetabular wear and loosening. The early results of total hip arthroplasty with noncemented acetabular components are promising, and many feel that they represent the state of the art. The hemispheric components with a porous coating have proven superior to most of the screw ring designs. There are potential disadvantages with the use of screws to augment fixation of the hemispheric components, and recently it has become popular to under-ream the acetabulum and press-fit the oversized acetabular component without the use of screws. PMID- 7874629 TI - Osseointegration of metal. AB - The healing response of bone to the injury of implant insertion is similar to its response to fracture. If there is absolute stability between the bone and the implant, the injury to the bone will result in bone formation, the bone growing and conforming to the surface configuration of the implant. There is first appositional bone growth and subsequently bone ingrowth into the interstices of the surface. The newly formed bone is not an uninterrupted layer of bone. It is mixed with well-differentiated fibrous tissue; only 13% to 20% of the bone is in contact with the implant. If the implant is relatively stable after insertion the healing response results in the implant becoming enveloped by dense organized fibrous tissue with occasional areas of fibrocartilage, without any areas of resorption in the surrounding bone. If the implant is unstable after insertion the healing response causes the implant to become surrounded by loosely organized fibrous tissue with active bone resorption occurring in the surrounding bone. PMID- 7874630 TI - Introduction. Hip disease in the young adult: a social as well as a medical dilemma. PMID- 7874631 TI - The case for cementing all femoral components in total hip replacement. AB - Two important new observations underlie the recommendation that it is advisable to cement all femoral components of total hip replacement (THR). First, it is now clear that improved cementing techniques have remarkably extended the durability of the cemented fermoral fixation and markedly reduced the incidence of lysis. Second, the incidence of femoral lysis around all noncemented femoral components that have been reported with minimum 5-year follow-up is high, increasing and alarming. With good cementing in primary THR, the incidence of femoral revision for aseptic loosening at 15 to 18 years after the initial operation is only 2% to 3%, even in those 50 years of age and younger. Moreover, lysis is rare. Similarly, with improved femoral cementing, femoral revision is also far more effective. The juxtaposition of the excellent results with improved cementing and the high and rising lysis rates around noncemented femoral components clearly mandate the use of contemporary cementing procedures for all femoral components, regardless of the age or sex of the patient, the diagnosis and whether the procedure is a primary or revision one. PMID- 7874632 TI - Appropriate imaging studies and their interpretation. AB - Imaging studies are essential for the diagnosis and management of many of the hip disease entities dealt with in this symposium. This paper briefly touches on salient aspects of standard radiography, "special" views, arthrography, radioisotope imaging, computed tomography and magnetic resonance imaging. Orthopedic surgeons must be familiar with the correct applications and interpretation of these modalities so as to use them efficiently and economically. PMID- 7874633 TI - Total hip replacement: the case for noncemented femoral fixation because of age. AB - Both noncemented fixation and improved cemented fixation of total hip replacements emerged to counteract the clinical and radiographic failures of early cemented procedures. A randomized clinical trial comparing a second generation cemented with a second-generation noncemented total hip replacement demonstrated that in the medium term both implants allow excellent, disease specific, global and functional capacity outcome measures. No significant differences existed between the cemented and noncemented implants in terms of these parameters or revision rate. Cost-to-utility analyses of both types of replacements revealed that total hip replacement is one of the most cost effective medical interventions. Noncemented total hip replacements seem as efficacious as cemented devices in patients younger than 70 years. PMID- 7874634 TI - Epilogue. The imperative for truly scientific outcome analyses. AB - Randomization is the best method of obtaining comparable groups in clinical trials, yet it is seldom used to compare one surgical treatment with another. The use of historic controls or unblinded randomization can lead to bias in selection and to questionable outcome results. The publication of clinical studies that are unblinded and not randomized should be questioned. PMID- 7874635 TI - Where is the missing piece of the jigsaw puzzle? PMID- 7874636 TI - Clinical nurse specialist and staff nurse colleagues in integrating nursing research with clinical practice. AB - To advocate for cost-effective patient care and to strengthen the registered nurse's professional practice, the CNS must support nursing research in acute care facilities. This support for research includes sparking the staff nurse's interest and involvement in all segments of the research process. We must recognize our clinical nurses' efforts on behalf of research through greater financial reward; the CNS is challenged to use his or her influence to persuade administrators to grant this support. How the CNS and staff nurse, working together, can disseminate the findings of nursing research, thus promoting cost effective care and solidifying the nurse's professional practice, is discussed in this article. PMID- 7874637 TI - Opportunities for the advanced practice nurse: encroachment or collaboration? PMID- 7874638 TI - Enhanced role opportunities available to the CNS/nurse practitioner. AB - Role possibilities that could result from the proposed CNS-nurse practitioner merger into an advanced practice nurse role are examined in this article. A brief history of the movement to merge the two roles is reviewed, followed by a review of arguments for and against merging. Role opportunities are explored for nurses with advanced practice preparation, including case management, expanded roles in acute care, practice in nurse-managed clinics, and collaborative private practice. PMID- 7874639 TI - The challenge of detection and management of alcohol abuse among elders. AB - Alcohol abuse and dependence, defined in the Diagnostic and Statistical Manual of Mental Disorders (3rd edition, revised), is a serious mental health problem in older adults. It affects an estimated 2.5 million older adults. The true extent of alcohol abuse and dependence among elders is likely even greater as many problem drinkers go undetected. Alcohol abuse can seriously predispose the elderly to accidents, nutritional deficiencies, and diseases, and eventually result in loss of independence. The purpose of this article is to (1) describe the profile of older alcoholics in the acute care setting who typically mask as medical management seekers, (2) relate some of the difficulties involved in accurately identifying the problem of elder alcohol abuse, and (3) suggest strategies to improve intervention by CNSs. PMID- 7874640 TI - Alternatives to physical restraints in acute care. PMID- 7874641 TI - Managing survey results. PMID- 7874642 TI - Nursing administrators' perceptions of critical care CNSs. AB - The literature has demonstrated inconsistencies among nursing administrators in their perceptions of the CNS role functions. Nursing administrators from 198 hospitals were surveyed: (a) to determine the current use of the critical care CNS, (b) to identify the importance placed on the critical care CNS role functions (expert clinician, educator, consultant/change agent, researcher, manager), (c) to ascertain perceptions of specific activities related to each role function, and (d) to determine any differences in perception of role functions between administrators who employed critical care CNSs and those who did not. Nursing administrators who employed critical care CNSs ranked the role of expert clinician as most important, followed by educator, consultant/change agent, and researcher. The role of manager was ranked least important. Nursing administrators who did not employ critical care CNSs ranked the roles in the following order of importance: expert clinician, educator, consultant/change agent, manager, and researcher. PMID- 7874643 TI - A survey of practicing nurses' research interests and activities. AB - We conducted a survey of 279 practicing nurses' research attitudes, past and current research activities, and research resources. Levels of practice included staff nurses, nurse managers, and advanced practice nurses. Three factors were identified from a 15-item research attitudes scale: research value, confidence, and perceived support. Significant differences were found for research value and confidence among three levels of clinical practice. Advanced practice nurses reported higher research value and confidence than did staff nurses and nurse managers. Most respondents reported using research findings in practice, but only a small percentage were conducting research. Factors related to research conduct and use differed. Suggestions are offered for methods to increase the value of research by practicing nurses. PMID- 7874644 TI - A time for education. PMID- 7874645 TI - An understanding of compassion in Nepo's Acre of Light. PMID- 7874646 TI - Does a shared name mean shared functions? PMID- 7874647 TI - Reducing restraint use in a nursing home. AB - Use of physical restraints in U.S. nursing homes has, historically, been quite high. Myths about restraints, e.g., that they prevent falls and injuries, have helped to perpetuate a practice that almost always results in long-term adverse physical and psychological effects for the resident. Recent federal law has severely restricted the use of physical restraints in nursing homes. Changing this practice of nursing home personnel requires a well thought out process and the cooperation of leaders in the facility. CNSs are uniquely qualified to move a facility toward the goal of reducing the use of restraints. Their skills as leaders, educators, change agents, consultants, and systems experts are most essential. PMID- 7874648 TI - Restructuring the CNS role for a managed care environment. AB - The CNS role in a large northeast teaching hospital was the focus of a major organizational change process in response to a tightening fiscal environment. CNSs worked with the nurse executive team to restructure their role from expert consultant to case manager, nurse manager partner, and resource and consultant to the Department of Nursing. Development needs of the CNSs were assessed before and after role revision to evaluate the process and provide evidence of learning and change. The change and learning process evidenced in this article exemplifies the CNSs' ability to adapt and respond to the rapidly changing needs of today's managed care setting. PMID- 7874649 TI - Gaining visibility for CNS recommendations. PMID- 7874650 TI - The development of CNS consultation forms. AB - Consultation is an essential part of CNS practice. Communication of information completes the consultation process and allows for quality care to be provided by all members aware of the consultation. Therefore, it is important to document the consultation clearly. How one CNS group addressed this issue is described. PMID- 7874651 TI - Psychiatry--a partner for change. PMID- 7874652 TI - Mandatory training in geriatric psychiatry: can programs deliver the goods? AB - There have been a number of recent attempts to establish guidelines and curricula for training of general psychiatry residents in geriatric psychiatry. However, concerns have arisen as to whether or not many training programs have the resources necessary to train residents using these guidelines. In an attempt to determine how closely training guidelines are adhered to, the Division of Geriatric Psychiatry at the University of Toronto anonymously surveyed all general psychiatry residents completing their mandatory training in geriatric psychiatry between June 1992 and July 1993 (N = 30). The supervisors of these residents were surveyed anonymously as well (N = 15). The response rate was 83% for the residents and 80% for staff. In general, the training guidelines were closely adhered to except possibly for the required number of patient contact hours per week. The author concludes that when training guidelines are developed which include consideration of appropriate program resources and the number of residents required to train, residents and supervisors adhere closely to these guidelines. PMID- 7874653 TI - Children, psychiatrists and the courts: understanding the ambivalence of the legal profession. Part 1--General principles. AB - Psychiatrists and other mental health professionals are frequently involved as expert witnesses in court proceedings related to children and adolescents. Their testimony may be based on a therapeutic relationship, but frequently arises because of an assessment conducted specifically for the court process. This two part paper discusses some of the issues that arise when child psychiatrists are involved as expert witnesses in litigation, with specific focus on their role in child custody, sexual abuse and young offender cases. It also offers some practical advice for those who may be called as witnesses. There is controversy in the legal profession about the role of mental health professionals in the court process. While there is recognition of their expertise, there is also a concern about not wanting to have experts usurp the role of the courts. Legal professionals also question the "objectivity" of experts, and the reliability of their opinions. Frequently the opinions of psychiatrists about children and adolescents involved in litigation have inherently speculative and value based dimensions, and not "scientific". Participation in the court process by mental health experts is nevertheless a vitally important role, providing information, analysis and recommendations about what are often very difficult societal decisions. Part two of this paper starts on page 531. PMID- 7874654 TI - Children, psychiatrists and the courts: understanding the ambivalence of the legal profession. Part II--Applied principles. PMID- 7874655 TI - Severity as a diagnostic dimension of borderline personality disorder. AB - The purpose of this study was to identify diagnostic and severity subgroups within a cohort of patients with borderline personality disorder (BPD). Of 171 patients clinically diagnosed with BPD, 132 were Diagnostic Interview for Borderlines (DIB) positive. Through a process of random selection, 41 of the DIB positive subjects were also interviewed with the revised version of the DIB (DIBR) and approximately one half with two semi-structured research interviews, the Schedule for Affective Disorders (SADS) and the Personality Disorder Examination (PDE). All subjects completed four self-report measures of problematic behaviours, symptoms and social adaptation. The analyses included examination of: 1. the correspondence of the BPD diagnosis across the DIB, the DIBR and the PDE; 2. the association between DIBR scoring levels and scores on measures of symptoms and behavioural status; and 3. the co-occurrence of BPD with Axis I and other Axis II disorders. Correlations and analyses of variance between both the DIB and DIBR scoring levels and the scores on the four symptom and behavioural measures showed that the scoring levels (DIB 7 to 10; DIBR 8 to 10) could be used to distinguish three subgroups of BPD. The three groups differed in terms of concordance for BPD with the PDE and in terms of patterns of overlap with DSM-III-R, Axis I and other Axis II disorders. This study shows that BPD subgroups can be located on a continuum of symptomatic and behavioural severity and that each subgroup has a specific pattern of overlap with Axis I and other Axis II disorders. PMID- 7874656 TI - [Involvement of the basal ganglia in obsessive compulsive disorder: a review]. AB - This article reviews the main clinical indicators linking the basal nuclei to obsessive compulsive disorder (OCD). Various pathologies associated with lesions of the basal nuclei are examined, followed by a review of neuropharmacological, brain imaging and psychosurgical studies. Once the role of the neostriatum in ritualistic behaviours has been clarified, the symptoms of OCD are interpreted based on the hypothesis of a lesion of the striato-orbito-frontal loop. PMID- 7874657 TI - Frequency of electroconvulsive therapy use at a provincial mental hospital: a retrospective study. AB - In this retrospective study the frequency of electroconvulsive therapy use in the Waterford Hospital, a provincial mental hospital over a period of 14 years is examined. The results indicate that the use of electroconvulsive therapy has declined significantly. The three local general hospitals, St. Claire's Mercy Hospital, The Grace Hospital and the General Hospital have also experienced a decline in the use of electroconvulsive therapy. The potential reasons for this decline are explored and the findings are discussed particularly in the context of a 1986 study that found high rates of electroconvulsive therapy use at the Waterford Hospital. PMID- 7874658 TI - Predicting outcome in a multimodal day treatment program for children with severe behaviour problems. AB - The demand for day treatment programs for children with severe behaviour problems has greatly increased in the past decade. The objective of this study is to identify characteristics of children who benefit most from such a program. The sample consisted of 63 children, aged five to 13, assessed at admission and discharge from the program. Outcome measures included behavioural improvement and school reintegration. At admission, multivariate analyses revealed that children who made the greatest behavioural improvements had less severe behaviour problems, lower IQ scores and more disturbed family functioning. Children reintegrated into regular classes after discharge were younger at admission, had better reading skills, no attention deficit hyperactivity disorder and little parental marital discord. Findings suggest that successful outcome can be predicted from characteristics of children at intake. A multimodal approach is needed to address the different problems areas in a child's life. PMID- 7874659 TI - A comparison of American and Canadian teachers' knowledge and attitudes towards Attention Deficit Hyperactivity Disorder (ADHD). AB - The purpose of this study was to compare and contrast American and Canadian teachers' knowledge and attitudes regarding ADHD. Both samples completed a self report questionnaire. The first part determined the demographic background of the teachers. The second section consisted of 20 true/false questions concerning ADHD intended to assess teachers' general knowledge of the essential concepts involved in the diagnosis and treatment of the disorder. The results indicated that both samples had little in-service training regarding ADHD. Despite this, most teachers regarded ADHD as a valid diagnosis with educational implications and wanted more formal training. While most teachers did well on knowledge-based questions regarding the etiology and educational implications of the condition, many still perceived non-medical therapies such as diets as being effective. Many regarded the condition as being outgrown at adolescence. Significantly, only 14% of the teachers had been involved in the diagnosis and ongoing monitoring of mediation by outside professionals. The implications of improved in-service training for all professionals involved with children with ADHD are discussed. PMID- 7874660 TI - The role of marital therapy in the treatment of depressed married women. AB - The absence of a close, confiding relationship has been identified as a vulnerability factor to depression for women under adverse circumstances. Marital discord has also been identified as a risk factor in initiating and sustaining depression in women. Recent research has suggested that marriages with a depressed spouse are associated with lack of intimacy and decreased self disclosure. This paper reviews three controlled outcome studies which demonstrate that marital therapy in combination with antidepressant medication is not indicated for hospitalized women with major affective disorder but either alone or in combination with antidepressants, marital therapy is a viable treatment for outpatient women who are suffering from depression. PMID- 7874661 TI - [Association between depression, temperament and personality disorder: some therapeutic implications]. AB - Certain personality traits or disorders in combination with clinical signs complicate the diagnosis and treatment of depression. The approaches to the relationships between personality and mood disorders vary. Some see important links between normal personality types (or temperaments) and depression, while others see certain temperaments as sub-syndromic variants of mood disorders. Finally, a third approach proposes an analysis, drawing on Robins and Guze's criteria, of the validity of psychiatric diagnoses for determining whether this frequent comorbidity of depression and personality disorders (DSM-III) is consistent with a nosologic relationship, or is merely some definitional or other artefact. A category-based diagnostic approach provides little clarification; in some studies, a dimensional model attempts to better define the links between depression, temperament and personality and clarify the content of the apparently heterogeneous notion of depression, with therapeutic implications. Research in this area should lead to the development of increasingly specific therapeutic approaches to depression. PMID- 7874662 TI - Delusional misidentification syndrome. PMID- 7874663 TI - Putative fluoxetine-related suicidality. PMID- 7874664 TI - Buspirone in the treatment of separation anxiety in an adolescent boy. PMID- 7874665 TI - Attracting funding. PMID- 7874666 TI - Schizophrenia and manic-depression: separate illnesses or a continuum? AB - Kraepelin proposed that schizophrenia and manic-depression were distinct and separable disorders. This hypothesis has been challenged recently by proponents of the "unitary psychosis" theory which posits a continuum from unipolar to bipolar disorder, continuing through schizoaffective and schizophrenic illness. In reviewing symptom cluster data and family studies, the author suggests that there is no compelling evidence to indicate a common pathophysiology for schizophrenia and bipolar disorder. More problematic is a diagnosis of schizoaffective disorder which does not appear to be a stable clinical entity. This would suggest that schizoaffective disorder is not a true clinical syndrome but rather a phenotypic variation. PMID- 7874667 TI - The cost of schizophrenia. AB - In 1988, the management of mental illness in the United States cost an estimated $129.3 billion which comprises direct costs (hospital/institution costs, health care provider fees, prescription drugs), indirect costs (reduced/lost productivity due to morbidity or mortality) and other costs including productivity of family caregivers. The largest mental health care expenditure is for schizophrenia due to the high prevalence of this illness, early age of onset, and pattern of chronicity. This paper reviews three aspects of the care of schizophrenia that have an impact on cost: 1. prevention of relapse; 2. provision of community care; and 3. use of new antipsychotic medications. Better compliance, community-based care incorporating clinical case management and improved treatments can be expected to lower costs while improving the quality of life and social functioning of patients. PMID- 7874668 TI - Clinical relationship of extrapyramidal symptoms and tardive dyskinesia. AB - The author reviews the relationship between extrapyramidal syndromes (EPS) such as dystonia, akathisia and parkinsonism, and tardive dyskinesia (TD), characterized clinically by late-onset repetitive movements. While the pathophysiological mechanisms are unclear, neuroleptic-induced EPS have been shown to be associated with a higher risk of TD. The appearance of EPS, however, has not been shown to predict the occurrence of TD. It has been hypothesized that dopamine hypofunction resulting in EPS may lead to the development of dopamine receptor supersensitivity, thereby increasing the TD risk. If this theory can be validated in the clinical setting, atypical neuroleptics (for example, clozapine, risperidone) with a lower EPS liability may result in a lower incidence of TD. PMID- 7874670 TI - Substance use disorders and mental illness: the relevance of comorbidity. PMID- 7874669 TI - Social dysfunction and mental illness in a community sample. AB - The purpose of this study was to determine the extent of the association between psychiatric disorders and various social problems. The Diagnostic Interview Schedule was administered to a community sample of 3258 individuals and the association between eight "core" psychiatric disorders and eight social problem behaviours was determined. The results confirmed findings from many clinical studies that had previously found a strong relationship between social problem behaviours and mental illness. However, certain disorders tended to be associated with specific problems. In addition, a positive association was found between the number of social problems exhibited and the prevalence of psychiatric disorder. These data suggest the presence of a common underlying factor (or factors) and call into question the common practice of creating separate services for each definable social problem that arises. PMID- 7874671 TI - A neural network model of cortical information processing in schizophrenia. II- Role of hippocampal-cortical interaction: a review and a model. AB - This paper considers the relevance of hippocampal dysfunction to symptom production in schizophrenia with the help of an integrative computational model of cortical processing. First, evidence for involvement of the hippocampus was systematically reviewed. Then, a neural network model of hippocampal-cortical interaction was proposed. The effects of a dysfunction in hippocampal-cortical interaction were explored through simulation experiments. Neural network simulation demonstrated that when the hippocampal function of classification and reduction of overlap in input is sub-optimal, increasing correlation among input patterns compromised storage capacity of the cortical network. Hippocampal dysfunction predisposes to the emergence of spurious retrieval states in cortical information processing. This provides a model for psychotic symptom formation in schizophrenia. PMID- 7874672 TI - [Correlation between symptoms and social adjustment in patients suffering from schizophrenia or major affective disorder]. AB - With a view to examining the appropriateness of relying solely on pharmacotherapy rather than on a program of multimodal therapy, the goal of this study is to test the hypothesis that there is little relationship between psychotic and affective symptoms on the one hand, and life skills and social functioning on the other. Eighty-four male subjects presenting a diagnosis of schizophrenia, mania or severe depression were therefore recruited in hospitals in the Montreal region. The relationships previously identified were studied, while factors likely to affect them, such as the chronicity of the disorder, the level of intellectual functioning, and the presence of additional symptoms, were controlled as necessary. The results suggest poorer social functioning among the schizophrenics having a high level of negative symptoms. In addition, the relationship between negative symptoms and IQ suggests that the intellectual functioning of these individuals can potentially affect the acquisition of skills required for adequate social functioning. Among subjects with a major affective disorder, the results reveal poor social functioning even during quasi-asymptomatic periods. These results suggest that patients suffering from schizophrenia or a major affective disorder require interventions aimed at increasing their level of psychosocial functioning. PMID- 7874673 TI - Self-concept and self-consciousness in adults with Tourette syndrome. AB - The hypothesis that adults with Tourette Syndrome (TS) have a lower level of self concept and a higher level of public self-consciousness and social anxiety than the general population was examined. Ninety-eight suitable adults responded to a letter distributed to the members of the Tourette Syndrome Foundation of Canada. The findings indicated that the group with TS and high obsessive-compulsive symptoms, but not TS alone, had significantly lower self-concepts than the general population. Both males and females with TS and high obsessive-compulsive symptoms scored higher on social anxiety than the general population, but no differences in public self-consciousness were found. The results of this study argue that people with TS alone do not have impaired self-concepts or social anxiety, but both of these disorders tend to be present among those who suffer from both TS and significant obsessive-compulsive symptoms. PMID- 7874674 TI - A treatment for impulse control disorders and paraphilia: a case report. AB - An individual with pedophilia and trichotillomania was treated with sertraline. Despite a longstanding history of trichotillomania, his hair-pulling behaviour stopped. In addition, pedophilic impulses also remitted. This improvement was noted not only in terms of subjective reporting but also in terms of biological and physiological testing done before and after treatment. PMID- 7874675 TI - Eastwood's lament. PMID- 7874676 TI - Hello Dr. Alzheimer. PMID- 7874677 TI - Re: Multiple personality. PMID- 7874678 TI - Re: Multiple personality. PMID- 7874679 TI - Fluoxetine for the prolonged treatment of schizophreniform psychosis. PMID- 7874680 TI - An alert to extrapyramidal side-effects from SSRIs. PMID- 7874681 TI - Student apathy: a footnote in the history of psychiatry or a disorder unique to post-adolescence? PMID- 7874682 TI - Visual-perceptual abnormalities in delusional misidentification. AB - Delusional misidentification syndromes are often found in conjunction with visual perceptual abnormalities. These abnormalities appear to be independent of visual hallucinations and are illusory in nature. A case of delusional misidentification with visual-perceptual abnormalities is presented. Cognitive and visual phenomenology suggests that careful recording of visual abnormalities may shed light on the relation between delusional misidentification and abnormal visual cognition. PMID- 7874683 TI - Borderline personality disorder and substance abuse: consequences of comorbidity. AB - The objective of this paper was to examine the prognostic significance of borderline personality disorder (BPD) and substance abuse in a cohort of former inpatients screened for BPD and followed up prospectively seven years after the index admission. The impact of comorbidity on borderline psychopathology, impulsivity and psychosocial functioning was examined. The original cohort was assembled between April 1983 and December 1985. Admissions were screened for borderline characteristics which resulted in a sample of 130 subjects, 88 of whom were positive for BPD based on the Diagnostic Interview for Borderlines. At seven years follow-up, 81 out of 130 (62.3%) subjects were re-interviewed. Six (4.6%) had committed suicide, two (1.5%) were deceased and 41 (31.6%) were lost to follow-up. The subjects with BPD and substance abuse were significantly differentiated from subjects with BPD only, substance abuse only and neither disorder on the basis of demonstrating more borderline psychopathology and more self-destructive and suicidal thoughts and behaviours. Probands with initial diagnoses of BPD and substance abuse were twice as likely to be diagnosed BPD on follow-up as probands with initial diagnosis of BPD only (relative risk = 2.19, 95% CI, 1.21 to 3.97). These findings and other research suggest that patients with comorbid BPD and substance abuse should be encouraged to focus on their abuse problems as a priority. PMID- 7874684 TI - Expression of type VI collagen during glioblastoma cell invasion in brain tissue cultures. AB - Human glioblastoma cells, U-87 MG, were utilized in two separate rat brain tissue culture systems. In both cases, the glioblastoma cells deeply penetrated and formed tumor masses inside the brain tissues. Immunofluorescence technique, utilizing anti-type VI collagen antibodies demonstrated strong immunoreactivity of type VI collagen in the tumor masses, invading cells, and cell groups. We suggest that type VI collagen may be involved in tumor cells infiltration and invasion of healthy rat brain tissues. Furthermore, the brain tissue culture method may provide a rapid in vitro model with which cellular and extracellular determinants of invasiveness may be studied. PMID- 7874685 TI - Effect of 5-fluorouracil on methotrexate transport and cytotoxicity in HT29 colon adenocarcinoma cells. AB - Exposure of the human colon adenocarcinoma HT29 cells to different concentrations of 5-fluorouracil (5FU) for 24 h resulted in a dose-dependent increase in the cellular glutathione (GSH) level which remained elevated up to 72 h following 5FU treatment. Pretreatment of HT29 cells with 5FU was found to enhance the uptake of methotrexate (MTX) as compared to control cells. Administration of MTX 24 h after 5FU was found to be synergistic, whereas administration of MTX 24 h before 5FU or together with 5FU was not found to be synergistic. The results of this study suggest that the increase in cellular GSH level as a result of 5FU pretreatment may play a role in the enhancement of MTX uptake and the cytotoxicity of both drugs in HT29 cells. PMID- 7874686 TI - Methylene blue induces cytotoxicity in human brain tumor cells. AB - Methylene blue (MB), a known inhibitor of guanylyl cyclase, induced cytotoxicity in SK-N-MC human neuroblastoma and U-373 MG human astrocytoma cells in a dose dependent manner. MB did not significantly alter cellular levels of cGMP in both cells. 8-Br cGMP, a membrane-permeable analogue of cGMP, did not decrease MB induced cytotoxicity, indicating that cGMP may not be a major target of the cytotoxic action of MB. However, hydroxyl radical scavengers or intracellular Ca2+ modulators effectively blocked the MB-induced cytotoxicity. These results suggest that hydroxyl radical and intracellular Ca2+ may have an important involvement in the cytotoxic action of MB. These results further suggest that the treatment with MB may be useful for the therapeutic applications of human brain tumors. PMID- 7874687 TI - The overexpression of int-5/Aromatase, a novel MMTV integration locus gene, is responsible for D2 mammary tumor cell proliferation. AB - Our recent studies have shown that the cellular gene at the mouse mammary tumor virus (MMTV) integration site in the int-5 locus in BALB/c D2 precancerous hyperplastic alveolar nodules is identical to the gene encoding aromatase (CYP19), a member of the cytochrome P450 gene superfamily. MMTV integrated within the 3' untranslated region of the aromatase gene is responsible for the overexpression of this gene (int-5/aromatase) in mammary tumors. This paper describes the biological significance of overexpression of int-5/aromatase in D2 tumor cells. Using a cell line derived from the D2 tumor, we have demonstrated the effect of the aromatase substrate, androstenedione, on the proliferation of tumor cells. Proliferative effects of androstenedione were blocked by an aromatase inhibitor, providing evidence for the role of int-5/aromatase in this process. Furthermore, the androstenedione-mediated proliferation was inhibited by the addition of anti-estrogen ICI 164,384, suggesting that the estrogen formed from the conversion of androstenedione by int-5/aromatase acts like a mitogen to stimulate the growth of D2 tumor cells. This model with its known mechanism of aromatase activation should prove useful for studying the role of intra-tumoral estrogen in mammary cancer, for evaluating the effects of aromatase inhibitors, and for comparing breast cancer treatments. PMID- 7874688 TI - Cytotoxic and mutagenic effects of ferric nitrilotriacetate on L5178Y mouse lymphoma cells. AB - An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal tubular necrosis that leads to a high incidence of renal adenocarcinoma in rodents. Others have shown that Fe-NTA induces modified DNA base products both in vitro and in vivo. However, Fe-NTA is negative in the Ames Salmonella test with or without S9 activation. The goal of this project was to determine if Fe-NTA is cytotoxic and mutagenic using the L5178Y (TK +/-) mouse lymphoma assay. Our experiments showed a relationship between the concentration of Fe-NTA (0 to 1 mM) and the decrease in relative survival. An exposure-dependent increase in the number of mutations was observed with increasing concentrations of Fe-NTA. At 14% relative survival, there was about a 4-fold increase in mutations (trifluorothymidine resistance) over unexposed, control cells. Ferric nitrate or nitrilotriacetic acid alone induced a relatively low 1.5- or 1.1-fold increase in mutation, respectively. Our results establish that Fe-NTA is mutagenic in the L5178Y mouse lymphoma assay system. PMID- 7874689 TI - Modulatory influence of camphor on the activities of hepatic carcinogen metabolizing enzymes and the levels of hepatic and extrahepatic reduced glutathione in mice. AB - The present paper deals with the modulatory influence of camphor on the activities of hepatic phase I and phase II drug metabolising enzymes and the levels of hepatic and extrahepatic reduced glutathione contents in the mouse. Female Swiss albino mice (8-9 weeks old) were treated daily by oral route for 20 days with 50, 150 or 300 mg/kg body weight of camphor dissolved in 0.1 ml of olive oil. Camphor only at the 300 mg/kg body weight dose level caused a significant increase in the activities of cytochrome P450 (P < 0.05), cytochrome b5 (P < 0.05), aryl hydrocarbon hydroxylase (P < 0.05) and glutathione S transferase (P < 0.05). These modulatory effects were comparable with those induced by 0.75% BHA diet given for 20 days (positive control group). The reduced glutathione level was elevated significantly in liver (P < 0.05) by camphor only at the 300 mg/kg body weight dose level and in liver, lung and stomach (P < 0.05) by BHA. PMID- 7874690 TI - An M(r) 7-kDa membrane protein overexpressed in human multidrug-resistant ovarian cancer cells. AB - We have developed a monoclonal antibody (designated 1D7) which recognizes an M(r) 7-kDa plasma membrane protein overexpressed in ovarian MDR cancer cells. The expression of the M(r) 7-kDa protein in various human multidrug-resistant and drug-sensitive cell lines was analysed by Western blot and flow cytometry methods. The small molecular weight protein was overexpressed in the human ovarian carcinoma cell line, SKVLB which was selected for vinblastine resistance from SKOV3 cells and in OVCAR 4/ADR100 and OVCAR 4/VBL200 which were generated from NIH:OVCAR4 by stepwise selection against adriamycin and vinblastine, respectively. Only a minor amount of the M(r) 7-kDa protein was found in the parent cell line, SKOV3. It was not found in other drug-resistant human cell lines such as the vinblastine-resistant CEM cells (CEM/VLB300), the intrinsic MDR colon cell line HCT15 and the human MDR breast cancer cell line, MCF7/AdrVp. 1D7 specifically inhibited the proliferation of the resistant cells. Our results suggest that the expression of the M(r) 7-kDa protein on the plasma membrane of ovarian MDR cancer cells may be involved in a mechanism related to the proliferation of the drug resistant cancer cells. PMID- 7874691 TI - Selective farnesol toxicity and translocation of protein kinase C in neoplastic HeLa-S3K and non-neoplastic CF-3 cells. AB - We have reported earlier that farnesol, a 15 carbon isoprenoid, has inhibitory effects on the growth and viability of a variety of cultured cells of neoplastic derivation but is considerably less cytotoxic to cells derived from normal tissue (Cancer Lett., 79, 175-179). As part of our search for the mechanism of this observation, we have studied the effect of 20 microM farnesol on the distribution of protein kinase C (PKC) between cytosolic and membrane fractions of HeLa S3K cells and fibroblasts line CF-3. In HeLa cells farnesol caused translocation of PKC from membrane fraction to cytosol after 1h of incubation and also prevented PMA-stimulated induction of PKC translocation from cytosol to membranes. Up to 6 h of incubation, there was no effect of farnesol on PKC localization in CF-3 fibroblasts. The results point to possible involvement of PKC in the toxic effect of farnesol which occurs with some degree of selectivity depending on cell origin. PMID- 7874692 TI - PAF and haematopoiesis. IV. Modifications of spleen and thymus PAF contents after a single dose of the chemotherapeutic drug 5-fluorouracil in mice. AB - The spleen and thymus of mice were examined for the presence of PAF after injection of 5-fluorouracil (5-FU) (200 mg/kg). A significant increase of the spleen (P = 0.005) and thymus (P < 0.05) PAF concentrations was noted 48 h after 5-FU infusion. PAF levels in thymus are similar to those of controls from days 4 to 14. By contrast, spleen PAF significantly decreased (0.005 < P < 0.03) from days 7 to 14. Conversely, the 5-FU administration did not modify the spleen and plasma acetylhydrolase activity, suggesting that the variations of PAF levels in thymus and spleen were mainly due to differences of local PAF production. Thus, the chemotherapeutic drug 5-FU modulates in vivo PAF production in haematopoietic organs of mice. Considering the effects of PAF in the processes of B- and T-cell proliferation and functions, these results could be of importance for the role of PAF during human cancer therapy and haematopoiesis in vivo. PMID- 7874693 TI - Pharmacokinetic and therapeutic outcome in melanoma cells, of the administration of symmetric and asymmetric cationic photosensitizers. AB - The response of melanoma cell lines to a range of novel cationic photosensitizers based on either a protoporphyrin or a mesotetra(4-carboxylphenyl)porphine molecule, has been examined. The drugs varied in terms of either their symmetry or their side chain configuration. The effect of these variables on drug uptake and photodynamic cell kill were tested. The absorption wavelengths for the drugs were measured and a shift to the red was seen in the presence of cells. Drug uptake was measured and the cationic sensitizers had a relatively high uptake when compared to anionic HpD. The efficiency of the drugs in causing cell kill was expressed in terms of clonogenic cell survival. The asymmetric photosensitizers were more efficient in destroying mouse and human melanoma cells than the clinically used anionic HpD, which was in turn more efficient than the symmetric sensitizers tested. PMID- 7874694 TI - Further investigation of the effect of cholic acid on the induction, growth characteristics and stability of aberrant crypt foci in rat colon. AB - We previously reported that the colons of animals injected with azoxymethane (AOM) and fed a diet containing cholic acid (CHA) had lower numbers of aberrant crypt foci (ACF) than those in animals fed a control diet. To follow up on this observation, a series of studies was conducted to determine whether CHA affects the development of ACF in a dose- and time-dependent manner, and the possible mechanism(s) involved. Sprague Dawley male rats were injected with AOM (20 mg/kg s.c.), and one week later randomly allocated to groups fed diets containing 0, 0.05, 0.1 or 0.2% CHA by weight, for 4 weeks. Their colons were scored for the number size and location of ACF, number of crypts per ACF, and mitotic activity. It was observed that the number and size of ACF decreased with increasing levels of CHA. Mitotic activity was higher (P < 0.05) in the 0.2% CHA diet (CHA-diet) group compared to the 0% CHA group. To determine if timing of intervention with the CHA-diet was critical, rats were allocated to the CHA-diet before or after AOM injection. The ACF-reducing effect of 0.2% CHA diet was evident (P < or = 0.05) only after AOM injection. Intervention with the CHA-diet 4 weeks after AOM injection demonstrated that the diet eliminated and/or remodelled a large proportion (50%) of ACF which had developed within 4 weeks and inhibited the growth of those ACF that persisted. This effect was also associated with higher (P < or = 0.05) mitotic activity in the colon. Discontinuing the treatment of rats with the CHA-diet resulted in a rapid increase in the number of ACF in their colons, establishing that the growth inhibitory effect of the CHA-diet on ACF was reversible. In conclusion, it was demonstrated that the CHA-diet modulated the number of ACF by inhibiting their development and growth and by eliminating or remodelling a selected population of ACF. PMID- 7874695 TI - Immunotherapy in liver tumors: III. A new experimental model of metastatic liver tumors from colorectal carcinoma for cytokine therapy. AB - A new model of metastatic liver tumors in Wistar/Furth rats is introduced. A colorectal adenocarcinoma cell line (LDLX40) induced by 1,2-dimethylhydrazine was injected through one of the branches of the ileal mesenteric vein to develop metastatic liver tumors in rats. On day 30 after the inoculation of tumor cells, micrometastases were detected under microscopy in all animals that received tumor inoculation. Macrometastases in 87.7% of animals were found by either the tumor staining test or ultrasonography. No extrahepatic tumor developed in this tumor model. To observe the effects of different treatment strategies on metastatic liver tumors, 35 animals were randomly divided into four groups. Group I served as control. Group II underwent hepatic artery ligation (HAL). Group III received intraportal administration of recombinant interleukin-2 (rIL-2) and interferon alpha (IFN-alpha). Group IV had intraportal medication of rIL-2 and IFN-alpha + HAL (the IIH protocol). Results indicated that rapid tumor growth was seen in the control tumors. HAL produced little response to metastatic liver tumors as compared to the control group (P > 0.05). The combined application of rIL-2 and IFN-alpha showed an improved result, with 22% of tumor growth inhibition or regression (P < 0.05 compared to the control group). Twenty-eight percent of tumor growth restraint or regression was found in the group treated with the IIH protocol (P < 0.05 compared to the control group). We conclude that this new experimental model of metastatic liver tumors is reproducible, and that the IIH protocol is effective in the treatment of metastatic liver tumors in rats. These beneficial effects from the IIH protocol may be introduced into patients with metastatic liver tumors. PMID- 7874696 TI - Correlation between the radiosensitivity in vitro of clones and variants derived from a human melanoma cell line and their spontaneous metastatic potential in vivo. AB - With an experimental model of spontaneous lung metastases of human melanoma in immunosuppressed newborn rats, a large panel of clones and variants with different metastatic potential were derived from a single human melanoma parental cell line (M4Be). Seven clones and variants from M4Be were selected, respectively, for their low (parental, clone 1), intermediate (clones 2 and 3, subvariant 1-) and high (variant 1, subvariant 1+, clone 4) metastatic potential. This paper investigates the relationship between the in vivo metastatic potential of the eight cell lines and their sensitivity to ionizing radiation in vitro (range 0.05-7 Gy). The radiosensitivity was estimated from the mean inactivation dose, a parameter equal to the area under the survival curve plotted in linear coordinates. Examination of the eight survival curves, obtained with cells cultured for no more than five passages after defrost, shows that clone 1, subvariant 1- and the M4be parental line are the most radioresistant cells, clone 4 and subvariant 1+ are the most radiosensitive cells, while clones 2 and 3 and variant 1 showed an intermediate response to radiation. The metastatic potential in vivo of the parental line and the seven sublines is significantly correlated to their radiosensitivity in vitro: the higher the metastatic potential, the higher the radiosensitivity. PMID- 7874697 TI - The influence of the cysteine protease inhibitor L-trans-epoxysuccinyl-leucyl amido(4-guanidio)butane (E64) on photobiological effects of tetra(4 sulfonatophenyl)porphine. AB - Human cervix carcinoma cells of the line NHIK 3025 were exposed to light after 18 h incubation with tetra(4-sulfonatophenyl)porphine (TPPS4) in the absence or presence of the cysteine protease inhibitor L-trans-epoxysuccinyl-leucyl amido(4 guanidino)butane (E64) followed by 1 h in sensitizer-free medium. E64 changed the photochemical properties of TPPS4 in NHIK 3025 cells, i.e., TPPS4 fluorescence yield was enhanced 2.5-fold and photochemically induced lysosomal rupture and loss of cell bound TPPS4 were inhibited. Additionally, E64 slightly (10%) reduced the sensitivity of the NHIK 3025 cells to photoinactivation. This is not likely to be due to its inhibitory effect on protease activity, but correlates with its inhibition of lysosomal rupture. The present results indicate that the release of lysosomal cysteine proteases from the lysosomal compartments are of little or no importance in the photochemical inactivation of NHIK 3025 cells when TPPS4 is used as photosensitizer. PMID- 7874698 TI - [A KABP (knowledge, attitude, belief and behavior) study about AIDS among taxi drivers and hotel attendants in Beijing]. AB - This article reports the KABP study on 448 taxi drivers and 556 hotel attendants in Beijing for the first time in China. A self-administered questionnaire was used to investigate knowledge, attitude, belief and practice (KABP) about AIDS. In terms of knowledge, 23.8% of hotel attendants and 36.8% of taxi drivers did not know that contact with blood could transmit HIV. Thirtyfive percent of hotel attendants and 42.2% of taxi drivers did not believe that intravenous drug users were at high risk. Some drivers (13.6%) and hotel attendants (3.4%) reported having multiple sexual partners. Forty-one point nine percent of taxi drivers and 16.6% of hotel attendants preferred the idea of multiple sexual partners. Among hotel attendants, a negative association was found between knowledge about AIDS and multiple sexual behavior (P < 0.01). Regarding attitude toward condom use, 56.2% of taxi drivers and 47.8% of hotel attendants who have had a sexual experience thought that condom use interfered with sexual pleasure. Seventy-six point eight percent of taxi drivers and 79.8% of hotel attendants believed that they could change their behaviors in order to minimize the chances of getting HIV. This study indicates that HIV education is important in reducing the number of sexual partners and promoting the use of safe sex practices like condom use. Furthermore, as reported by the study population, education can change behavior. PMID- 7874699 TI - [Study on incidence of acute flaccid paralysis in Hebei]. AB - A study on the incidence of Acute Flaccid Paralysis (AFP) among 0-14 year-old children in 1990-1992 was carried out in all over 12 prefectures and cities level hospitals in Hebei. The county level hospitals were investigated in 3 of 12 prefectures and cities. A total of 214 hospitals were investigated. The result showed that the annual average incidence of AFP and non-polio AFP among 0-14 year old children in 1990-1992 were 1.498/100000 and 0.988/100000, respectively. The annual average incidence of them among < 5 year-old children were 2.917/100000, 1.591/100000, respectively. The incidence of AFP and non-polio AFP were different in each prefecture and city. GBS accounts for 54.06% of all AFP cases. PMID- 7874700 TI - [A new diarrhea pathogen: entero-SLTs-producing and invasive Escherichia coli was over-looked as normal flora E. coli]. AB - In clinical laboratories of Beijing, China, no known entero-pathogen but almost pure E. coli strains could be isolated from more than 60% fecal samples of diarrheal patients, which had been recognized as normal flora E. coli and dismissed. We suspected that some of the so-called normal flora E. coli strains might be virulent. To prove our idea. We collected 172 strains of E. coli isolated from diarrheal patients from whom no other enteric bacterial pathogens had been identified, including EPEC, EIEC, ETEC. With plasmid DNA analysis, Hep-2 cell adherence assay and 10 DNA probe hybridization, we found that the so-called normal flora E. coli was abnormal, 44% of them were virulent, of which 16 (9.3) were EHEC, 8 EPEC (4.7%), 11 EAggEC (6.8%). Fifty-four of 172 strains were hybridized with INV and SLT1 or SLT2 probes, which had never been reported. These strains could invade Hep-2 cells, but were lack of ipaB gene, a key gene of invasiveness gene cluster of Shigella species and EIEC. The aggregative adherence to Hep-2 cells was observed, but the strains were not hybridized with EAggEC specific DNA probe. The purified toxin protein and cell filtrate were toxic to vero cells. Based on the data obtained, we believed that this is a new category of diarrhea-genic E. coli, named as entero-SLTs-producing and invasive E.coli (ESIEC). ESIEC occupied 31.4% of the strains tested, the isolation of it was probably higher than those of ETEC, EPEC in P R China. PMID- 7874701 TI - [A study on the boundary value of hemoglobin concentration for screening iron deficiency anemia in pregnant women]. AB - To evaluate whether a pregnant woman is in anemia or there exist the needs to replenish iron is usually based on the measurement of hemoglobin (HB) concentration, because the evaluation of iron nutritional status has not yet been used widely in our country. Blood specimens were collected from 258 pregnant women, and concentrations of Hb, serum ferritin (SF) and free erythrocyte protoporphyrin (FEP) were determined to find out a reasonably boundary value of Hb concentration from the two different ones set by our country and WHO, respectively, and the one averaged the former two, i.e, 100g/L, 110g/L and 105g/L. False positivity and false negativity in diagnosis of iron deficiency anemia (IDA) for pregnant women were evaluated based on the measurement of SF and FEP concentrations as gold standards. Results showed that the optimal Hb concentration for preliminary diagnosis of IDA was 105g/L with maximizing Yorden index. PMID- 7874702 TI - [Interruption of perinatal transmission of HBV by Chinese recombinant hepatitis B vaccine]. AB - Sixty-two infants who were born from HBsAg and HBeAg both positive mothers were vaccinated with 20 micrograms/dose recombinant hepatitis B vaccine, which was made in Beijing Institute of Biologic Products (Vaccinia virus recombinant hepatitis B vaccine) and Changchun Institute of Biologic Products (Chinese hamster ovary cells recombinant hepatitis B vaccine), at 0, 1, 6 months. All the babies were followed up for 9 or 12 months. The results showed that the protective rates of Beijing vaccine and Changchun vaccine were 79.2% and 80.2%, respectively, the positive rates of anti-HBs were 78.8% and 79.3%, respectively. Local or systematic reactions were not found in all the babies 3 days after injection. These results suggested that the Chinese recombinant hepatitis B vaccine was safe and effective. It was better than the plasma vaccine with the same dose. PMID- 7874703 TI - [Observation on prevention of hepatitis B virus transmission from mother to baby by hepatitis B vaccine]. AB - Forty-two new-born infants whose mothers had been given HBV vaccine before marriage were undergone medical examination for six years. The results showed that the six-month seroconversion rates of anti-HBs among those infants, whose mothers had been immunized successfully, were 90.00% (9/10), and no one was infected by HBV. But the rates of those infants whose mothers were found to be HBsAg(+) and HBsAg/HBeAg(+) before or after marriage were 20.00% (2/10) and 18.18% (4/22), respectively, being much lower than the former. The rates of HBsAg(+) were 70.00% (7/10) and 68.18% (15/22), respectively. This led to the conclusion that immunization with HBV vaccine before marriage will partly break the HBV transmission chain of "couples-mother and her baby-population". PMID- 7874704 TI - [A study on relation between effect of HB vaccination and time of the second injection]. AB - Three kinds of hepatitis B vaccination schedule in neonates were compared. The schedule included 0, 40 day, 6 month; 0, 50 day, 6 month; 0, 60 day, 6 month; and was controlled by the 0, 30 day, 6 month schedule. The results showed that there was no statistically significant difference among three kinds of schedule, no matter who were neonates of HBs Ag-positive mother or neonates of HBsAg-negative mother. These indicated that in areas with poor condition, such as mountain, island, the second injection of hepatitis B vaccine in neonates may be completed within 30-60 days. PMID- 7874705 TI - [A study on serologic markers for screening before hepatitis B vaccination]. AB - Three serologic markers for screening before hepatitis B vaccination were HBsAg, anti-HBs and anti-HBc. The data of HB virus infection in eight cities were analysed in order to save test cost and to achieve similar immune effect. For routine screening, anti-HBc is the only one marker needed to be used. The neonates and children aged 0-3 years can be vaccinated directly without screening. PMID- 7874706 TI - [Assay of R-plasmid and antibiotic resistance spectrum in 286 strains of gram negative bacteria]. AB - This paper reports the results of the sensitivity test to 10 antibiotics and the assay of R-plasmid on 286 strains of Gram-negative bacteria isolated from hospitals. It was found that the main prevalent resistant bacteria are Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae. Their major antibiotic resistance spectrum is: Ampicillin, Carbenicillin, Chloramphemicol, Gentamicin, Furbenicillin. The results showed that 272 of 283 strains resisted to 1-9 antibiotics (95.1%). One-hundred and seventy-eight of 286 strains resisted to more than 4 antibiotics (62.2%). One-hundred and fifty-one of 286 strains carried R-plasmid in resistant bacteria (53.3%). 13.3% resistance markers were transferred with the whole R-factor. But 86.7% resistance markers were transferred with only a part of R-factor. PMID- 7874707 TI - [A new concept and method of standardizing predictive value]. AB - A new concept and method of standardizing predictive value was put forward. The theoretical predictive value which was not affected by prevalence rate or different component in normal and abnormal groups and was gotten under the appointed standardizing condition that made the cases in the two groups to be same with each other and to be called standardizing component was defined as standardizing predictive value. The value will change only with the change of sensitivity and specificity of diagnostic test. By the new concept and method, the value of diagnostic test can be explained, judged and expressed in unique standard. PMID- 7874708 TI - [Meta-analysis and its application in epidemiology]. AB - Meta-analysis provides a powerful statistical tool for epidemiological study. The basic principle of meta-analysis is introduced in this paper, and some problems about its application in epidemiology are discussed. This method was used by the authors to study the relationship between exposure to extreme low frequency electromagnetic fields (ELF) and childhood leukemia, and the result showed that there is a significant association between them. PMID- 7874709 TI - [Detection of anti-BB antibodies in human sera by VIDAS system]. AB - Lyme disease is an infectious disease just known in the latest decade. The sera of people from various origins were detected for Anti-BB antibodies (IgM+IgG) by VIDAS system. The results are as follows: Of 83 sera from the health-cared people, 8 were positive (9.6%); of 20 sera from the patients clinical diagnosed as tuberculosis, none was positive; of 46 sera from the patients clinical diagnosed or suspected as node diseases, 4 were positive (8.7%); of 57 sera from the patients with various ophthalmologic diseases, 13 were positive (22.8%); of 15 sera from the patients with stomatologic diseases, 4 were positive (26.7%); of 17 sera from the patients with various diseases including dermomyositis, liver and spleen swelling, undefined febrile diseases; lung cancer, lung shadow, etc.), 2 were positive (11.8%); of 16 sera from the people highly suspected with lyme disease living in the epidemic areas of Xin Jiang and Hei Long Jiang provinces, 12 were positive (75%). The same 165 sera samples were detected at the same time by VIDAS System and IFA, 24 were positive by VIDAS System (14.5%), and 131 positive by IFA (79%), the accordance rate was only 32.7%. PMID- 7874710 TI - [Current epidemiologic characteristics of measles and its tactics of immunization]. PMID- 7874711 TI - Comparison of three coronary stents: clinical and angiographic outcome after elective placement in 134 consecutive patients. AB - One hundred and thirty-four consecutive patients undergoing elective coronary stenting were studied to assess the relative performance of Palmaz-Schatz (PS), Gianturco-Roubin (GR), and Wiktor (W) stents. Eighty-six percent of patients underwent follow-up angiography. Initial and follow-up angiograms were assessed by a central angiographic core laboratory. Attempts were made to place 81 Palmaz Schatz (PS) stents, 21 Gianturco-Roubin (GR), and 32 Wiktor (W) stents. PS stents were less frequently successfully deployed (88% PS vs. 100% GR vs. 97% W; P = 0.03). The final percent stenosis was greater with the GR stent (32% GR vs. 14% PS vs. 19% W; P < 0.001). The restenosis rate was lower in the PS group (PS 48.2% vs. GR 66.7% and W 68.4%; P = 0.044). After accounting for the effect of prior restenosis (P = 0.005) and saphenous vein site (P = 0.006) in multivariate testing, lesion severity at follow-up was still less with the Palmaz-Schatz stent (P = 0.037). PMID- 7874712 TI - Comparison of 7 and 8 French guiding catheters for elective PTCA: results of a prospective randomized trial. AB - A prospective randomized trial was performed to detect technical and clinical differences of 7F compared to 8F guiding catheters (GC) used in elective coronary angioplasty (PTCA). One hundred and fifteen patients undergoing elective PTCA with standard balloon dilatation catheters were randomized to 7F (55 pts) or 8F (58 pts) guiding catheters. The endpoints were primarily coronary artery and peripheral vascular complications; and secondarily, technical details and quantitative and qualitative angiographic quality. There was no difference between 7F or 8F GC for development of coronary or peripheral vascular complications. With 7F GC there was less blood loss (Hct, 3.5 +/- 3.4% vs. 6.5 +/ 9.6%, P = .033), and less contrast medium (160 +/- 88 mL vs. 200 +/- 119 mL, P = .049) used. Angiographic quality was similar, although visualization of lesions in the left anterior descending coronary artery in the left anterior oblique projection was improved with the 8F GC. There is no advantage of 7F GC for the prevention of coronary or peripheral vascular complications, although there was less blood loss and contrast medium used with the 7F systems. PMID- 7874713 TI - Peripheral arterial access: the large and small of it. PMID- 7874715 TI - Clinical utility of intravascular ultrasound imaging. PMID- 7874714 TI - Coronary artery lumen volume measurement using three-dimensional intravascular ultrasound: validation of a new technique. AB - OBJECTIVE: To validate an automated algorithm for the measurement of lumen volumes of coronary arteries. BACKGROUND: Current intravascular ultrasound systems use absolute measurements of and changes in areas and diameters for the assessment of coronary artery disease. However, the coronary artery is a three dimensional structure of complex geometry and volume. METHODS: We used a comprehensive imaging system designed to reconstruct planar intravascular ultrasound images in three dimensions. This system consisted of a 25 MHz transducer-tipped rigid probe (for in vitro studies) or a 25 MHz transducer tipped catheter within a 3.9F monorail imaging sheath (for in vivo studies), a motorized catheter pullback device that withdrew the transducer at 0.5 mm/sec, and an image processing computer that stacked 15 image slices/mm of vessel axial length and then performed threshold-based three-dimensional image rendering and lumen volume measurement. We imaged 13 human coronary vessels (6 RCA, 6 LAD, 1 LCX) in vitro and 16 vessels (8 LAD, 6 RCA, 2 SVG) in vivo. RESULTS: IN VITRO STUDIES: Lumen volumes derived by three-dimensional intravascular ultrasound were 171 +/- 121 mm3 and compared very well with those derived by histology (160 +/- 109 mm3, r = 0.97, SEE = 29 mm3, P < 0.001) and with those derived by manual planimetry of planar intravascular ultrasound images (150 +/- 106 mm3, r = 0.97, SEE = 30 mm3, P < 0.001). In vivo studies: Lumen volumes derived by three dimensional intravascular ultrasound were 74 +/- 35 mm3 and compared well with those derived by quantitative angiography (52 +/- 20 mm3, r = 0.71, SEE = 25 mm3, P < 0.002). CONCLUSIONS: Three-dimensional intravascular ultrasound is a new technique that can accurately measure coronary artery lumen volumes. Further technical improvements may help to establish this technique as the new standard for lumen volume measurement. PMID- 7874716 TI - Retrograde nontransseptal balloon mitral valvuloplasty using a modified Inoue balloon catheter. AB - Retrograde nontransseptal balloon mitral valvuloplasty, a method developed in our institution for the treatment of symptomatic mitral stenosis, avoids transseptal catheterization. Until recently, the self-positioning Inoue balloon catheter, unlike all other commercially available balloon catheters, had not been employed in this nontransseptal technique due to the short length of its catheter shaft. To employ a self-positioning balloon in retrograde nontransseptal balloon mitral valvuloplasty, we modified the Inoue device by extension of the catheter shaft. After retrograde nontransseptal left atrial catheterization using a steerable cardiac catheter, the modified Inoue balloon catheter was inserted through the femoral artery and advanced to the mitral valve retrogradely. Valvuloplasty was performed in 20 patients, with a successful result achieved in all. The modified Inoue balloon catheter was easy to use in retrograde nontransseptal balloon mitral valvuloplasty and showed excellent stability during inflation. Mean mitral valve area increased from 1.0 +/- 0.29 to 2.23 +/- 0.64 cm2 (P < 0.001) and mean transmitral gradient decreased from 11.4 +/- 6 to 4.3 +/- 2.1 mm Hg (P < 0.001). No major or minor complications were observed. Retrograde nontransseptal balloon mitral valvuloplasty using a modified Inoue balloon catheter is a feasible and effective technique for the treatment of symptomatic mitral stenosis. It appears to combine the advantages of avoiding transseptal catheterization with the advantages of this balloon's special configuration. PMID- 7874717 TI - Restenosis presented with unstable angina and myocardial infarction: one explanation for late cardiac events following directional coronary atherectomy. AB - Three cases of restenosis after directional coronary atherectomy (DCA) presented with unstable angina and then myocardial infarction. Two of them were complicated with malignant ventricular dysrhythmia. A total or subtotal thrombotic occlusion at the DCA site was shown. This fulminating course of restenosis could partially explain the higher late cardiac morbidity and mortality after DCA than after percutaneous transluminal balloon angioplasty. PMID- 7874718 TI - Serial angiographic appearance of healing dissection after balloon angioplasty. AB - In this report we describe the case of a patient with a significant coronary artery dissection following percutaneous transluminal coronary angioplasty (PTCA) in whom serial coronary arteriograms were obtained over a 6-week period. These demonstrated healing of the dissected vessel and correlated with abatement of the patient's angina. PMID- 7874719 TI - Mechanical coronary artery shortening with vessel wall deformity during directional coronary atherectomy: first reported case involving the left anterior descending artery. AB - Coronary spasm, dissection, thrombosis, and mechanical coronary artery obstruction due to vessel shortening and deformity resulting from kinking, invagination, or collapse in an accordion-like fashion are recognized sources of iatrogenic obstruction during PTCA. Rapid recognition is required to initiate appropriate therapy. Described is the first reported case of mechanical obstruction involving the left anterior descending artery. PMID- 7874720 TI - Acute myocardial infarction in a young adult due to solitary giant cell arteritis of the coronary artery diagnosed antemortemly by primary directional coronary atherectomy. AB - It has been reported sporadically that several types of coronary arteritis can result in myocardial infarction. Recently, we treated a 27-year-old with acute anterior myocardial infarction. Primary directional coronary atherectomy was performed in order to recanalize the totally occluded coronary artery. The atherectomized tissue consisted of thrombi and intima infiltrated with inflammatory cells and multinucleated giant cells. Underlying diseases which can result in giant cell arteritis were excluded. This report documents that coronary arteritis can induce acute myocardial infarction, and that directional coronary atherectomy can be an effective tool in the diagnostic method for coronary arteritis. PMID- 7874721 TI - Rationale and application of coronary transstenotic pressure gradient measurements. AB - Presence, extent, and evolution of atherosclerotic coronary narrowings, as well as the anatomic possibilities for revascularization, can be reliably defined at (and only at) selective coronary angiography. The latter remains, therefore, the pivotal diagnostic tool for patients with suspected coronary artery disease. However, in spite of the increasing availability of on-line quantitative coronary angiography, it still holds that the functional (physiologic) consequences of an epicardial coronary narrowing cannot be completely derived from geometric (anatomic) information. Clinical decision making can be particularly difficult in lesions of intermediate severity (40-70% diameter reduction), in postinterventional segments, and in some particular anatomic settings, namely, ostial stenoses, bifurcation lesions, and diffuse atherosclerotic disease. This has led to an explosive growth of new methods for assessing the physiological significance of coronary narrowings documented at angiography. Among them, Doppler blood flow velocitometry and transstenotic pressure gradient measurements have emerged as the only techniques easily applicable in most catheterization laboratories. Here, we briefly review the clinical interest of measuring transstenotic pressure gradients. PMID- 7874722 TI - Transstenotic pressures: can there be a "low-tech" solution to a complex physiologic problem? PMID- 7874723 TI - Correct and spurious calibration of the Oxicom oximeter. AB - Oxicom oximeters are widely used in cardiac catheterization laboratories. To calibrate the Oxicom oximeter, samples of oxygenated and deoxygenated whole blood are first analyzed on a CO-Oximeter, and then the Oxicom is adjusted to agree with the CO-Oximeter's readings. Subsequently, the Oxicom's calibration is confirmed at frequent intervals by taking readings from a white plastic stick that is inserted into the instrument to simulate a blood sample. The data in this report demonstrate that the readings from the white plastic "test simulator" failed to detect an out-of-calibration condition. By contrast, when the Oxicom was carefully adjusted to agree with a CO-Oximeter's readings on arterial and venous blood, a linear calibration curve resulted, and the Oxicom achieved its specified accuracy (2.5%). The precautions necessary to calibrate the Oxicom correctly are enumerated in the text. PMID- 7874724 TI - Successful reversal of cardiogenic shock precipitated by saphenous vein graft distal embolization using aspiration thrombectomy. AB - A 74-year-old male had cardiac catheterization complicated by embolization of a thrombotic proximal saphenous vein graft lesion. Cardiogenic shock ensued. Successful aspiration thrombectomy was performed using a 7F multipurpose guiding catheter advanced to the site of obstruction. There was complete angiographic resolution and reversal of cardiogenic shock. PMID- 7874725 TI - Cath lab emergencies: quick thinking can save lives. PMID- 7874726 TI - Reversible coronary artery kinking caused by cardiopulmonary support. AB - Cardiopulmonary support is utilized to provide optimal hemodynamic stability in high risk patients undergoing percutaneous transluminal coronary angioplasty. This report describes a patient undergoing supported angioplasty in whom multiple new severe stenoses were noted following coronary dilation and that were completely reversed by discontinuing cardiopulmonary support. PMID- 7874727 TI - Video-assisted transportal pericardial window. AB - Pericardial interventions for the diagnosis and treatment of pericardial disease has been evolving since the 17th century. The controversy over opened or closed procedures, the optimal guidance modality, and techniques for the creation of pericardial windows continues to be debated. This report describes two patients who received the endoscopic approach to creating a pericardial window. PMID- 7874728 TI - Iliac compression: a rare hindrance to percutaneous mitral valvuloplasty. AB - Percutaneous mitral valvuloplasty using the Inoue technique was complicated by the failure to pass the dilator or balloon catheter above the vertebral level of L5 due to compression of the right common iliac vein by the right common iliac artery. The procedure was accomplished when a long sheath was used to pass the Inoue balloon catheter beyond the obstruction. PMID- 7874729 TI - Initial clinical application of a novel coronary angioplasty guide catheter exchange device. AB - The initial clinical experience with a novel device designed to facilitate guide catheter exchange during coronary angioplasty while maintaining a secure guidewire position (Marathon Relay, Baxter Interventional Cardiology, Irvine, CA) is described. Over a 7-month period, 23 guide catheter exchanges were attempted during 20 procedures. The angioplasty procedure involved the use of newer devices in 65% of attempts with coronary stent deployment in 50% of attempts. In the majority (57%) of cases, exchanges were performed to allow improved guide catheter support. The exchange procedure was successful in 91% of attempts. Ultimate procedural success was achieved in 95% of patients with no complications. In this early experience, this device was found to be safe and effectively facilitated guide catheter exchange. PMID- 7874730 TI - Stabilization of methionine-rich protein in Saccharomyces cerevisiae: targeting of BZN protein into the peroxisome. AB - We have constructed a gene coding for the 12-kDa intermediate form of the 2s methionine-rich protein from Bertholletia excelsa seeds. This protein, expressed intracellularly in yeast, is characterised by a 20-min half-life. By adding 11 amino acids corresponding to the peroxisome-targeting sequence (PTSc) of luciferase, we have significantly increased its half-life. This stabilization allowed accumulation of the BZN protein into the peroxisome as judged by cell fractionation. Accumulation of the 12-kDa protein results in a significant increase of the total methionine content in yeast cells (30%) indicating that such a microorganism could represent a practicable protected shuttle for an animal-feed additive. PMID- 7874731 TI - Cloning and molecular analysis of two different ILV5 genes from a brewing strain of Saccharomyces cerevisiae. AB - Two different ILV5 genes encoding acetohydroxy-acid isomeroreductases, and named ILV5G and ILV5X, were cloned and sequenced from a Saccharomyces cerevisiae brewing strain. The coding sequence of ILV5X shows a single nucleotide change with respect to that from the ILV5 gene of a S. cerevisiae laboratory strain. In addition, all promoter motifs which are, or are presumed to be, implicated in transcription regulatory functions are identical in ILV5 and ILV5X. In contrast, the coding sequence of ILV5G differs in 5.6% of its nucleotides from that of ILV5 and most of its promoter regulatory motifs show a single nucleotide change with respect to those from ILV5. PMID- 7874732 TI - A 61-kb ring chromosome shows an ARS-dependent increase in its mitotic stability in the mcm2 mutant of yeast. AB - We have studied the effects of ARS addition and deletion on the maintenance of a 61-kb ring derivative of chromosome III in a minichromosome maintenance mutant of yeast carrying the mcm2-1 mutation. When this ring chromosome, CIIIR, had either of its two strong origins deleted, the resultant chromosome showed a much greater instability in the mutant as compared to that of the wild-type strain. Integration of more ARSs improved the maintenance of CIIIR in the mutant but not in the wild-type strain. Increase in the size of CIIIR, without any ARS addition, did not improve the stability in either strain. A spontaneous revertant for improved growth at 35 degrees C also co-reverted for minichromosome and CIIIR maintenance. The results suggest that ARS malfunctioning leads to minichromosome and chromosome loss from mutant cells, affecting their growth at higher temperatures. PMID- 7874733 TI - cDNA cloning of a Sec61 homologue from the cryptomonad alga Pyrenomonas salina. AB - Sec61 is an endoplasmic reticulum transmembrane protein involved in the process of translocation of proteins across this membrane. To-date, the only cloned genes for Sec61 are derived from mammals and yeast. In this paper, we present the first full-length cDNA from a sec61 gene of a plant cell. Comparison of the predicted protein sequence with all known Sec61 proteins, as well as with the bacterial/plastome-encoded homologue SecY, demonstrates a high degree of similarity among the SecY/Sec61 family. PMID- 7874734 TI - MluI site-dependent transcriptional regulation of the Candida albicans dUTPase gene. AB - The Candida albicans dUTP pyrophosphatase (dUTPase) gene DUT1 has been isolated by genetic complementation in S. cerevisiae. It was found to encode a 17-kDa protein similar in amino-acid sequence to dUTPases isolated from other systems. The gene was adapted for expression in E. coli and yielded a soluble and highly active enzyme which is easily purified. The 5' flanking sequence of DUT1 contains an MluI site typical of MCB cell-cycle-dependent UAS elements of budding and fission yeast. We found the gene to be cell-cycle-regulated when expressed in S. cerevisiae, and deletion of the MluI site resulted in a large reduction of DUT1 transcription in C. albicans. These results suggest that MCB elements are functionally conserved in this pathogenic fungus. Based on the vital role that dUTPase plays in DNA replication, the C. albicans enzyme may be a potentially useful target for the development of novel anti-fungal compounds. PMID- 7874735 TI - Construction by one-step gene replacement of Trichoderma reesei strains that produce the glucoamylase P of Hormoconis resinae. AB - Two one-step gene replacement vectors containing either the Hormoconis resinae glucoamylase P (gamP) genomic gene or the corresponding cDNA, each under the control of the promoter of the Trichoderma reesei cellobiohydrolase 1 gene (cbh1), were constructed and used to replace the cbh1 gene in a T. reesei strain. In both vectors the cbh1 promoter is precisely fused to the gamP protein coding region. Both the gamP cDNA and the genomic gene direct the secretion of the active glucoamylase P (GAMP) enzyme from T. reesei, which indicates that the intron sequences in the genomic gamP gene are processed in T. reesei. According to the results, a T. reesei transformant strain, in which the cbh1 gene has been replaced by a single copy of the gamP genomic gene, secretes more active GAMP than does a transformant strain having three copies of the cDNA clone in tandem orientation at the cbh1 locus. PMID- 7874736 TI - The function and specificity of the C-terminal tripeptide glyoxysomal targeting signal in Neurospora crassa. AB - The function of the C-terminal tripeptide targeting signal responsible for microbody targeting in many eukaryotes has been investigated in the filamentous fungus Neurospora crassa. Using an in-vivo targeting assay that employs transformants carrying C-terminally-modified versions of the bacterial enzyme chloramphenicol acetyltransferase (CAT), it has been demonstrated that C-terminal tripeptide-dependent import occurs most efficiently in response to nutritional acetate-induction. Under these conditions Neurospora generates a specialized organelle, the glyoxysome, which carries the enzymes responsible for the glyoxylate cycle and can be distinguished from peroxisome-like microbodies that contain catalase. Moreover, several C-terminal peptides have been tested in this system to extend the tripeptide targeting consensus to A/C/G/S-H/K/Q/R-I/L/V. However, the tripeptide analogue, ARM, found at the C-terminus of the glyoxylate cycle enzyme isocitrate lyase in higher plants, does not apparently function here. PMID- 7874737 TI - The Pichia pastoris HIS4 gene: nucleotide sequence, creation of a non-reverting his4 deletion mutant, and development of HIS4-based replicating and integrating plasmids. AB - We have obtained a clone of the Pichia pastoris HIS4 gene and have determined its nucleotide sequence. Based upon its deduced amino-acid sequence, the product of the P. pastoris HIS4 gene has the same structural organization as the Saccharomyces cerevisiae His4 protein and appears to encode a trifunctional enzyme catalyzing the second (phosphoribosyl-ATP pyrophosphohydrolase), third (phosphoribosyl-AMP cyclohydrolase), and tenth (histidinol dehydrogenase) steps in histidine biosynthesis. The chromosomal copy of the HIS4 gene was disrupted by homologous recombination, creating the strain SGY58. The his4 delta deletion mutation in this strain lacks the entire coding region of this gene and has a reversion rate that is undetectable. A set of complementary plasmids that carry the HIS4 gene was also developed. Among these are nine E. coli-P. pastoris shuttle vectors that transform the his4 delta deletion mutant at high efficiency and an integration vector for creating site-specific alterations of the P. pastoris genome. PMID- 7874738 TI - The presence of a nucleomorph hsp70 gene is a common feature of Cryptophyta and Chlorarachniophyta. AB - Cryptomonad algae and Chlorarachniophyta are evolutionary chimaeras derived from the engulfment of an eukaryotic phototrophic endosymbiont by a eukaryotic host cell. Although much reduced, the endosymbiont's eukaryotic plasmatic compartment still contains a nucleus, the so-called nucleomorph. These nucleomorphs carry the smallest known eukaryotic genomes. We have characterized the genomes of several cryptomonads and a Chlorarachnion species by means of PFGE (pulsed-field gel electrophoresis). Hybridization studies with small subunit rDNA were used to identify the nucleomorph chromosomes. We also performed hybridization experiments with an hsp70 probe to estimate the distribution of this gene among the different algal species. The evolutionary, genetical, and physiological implications of our studies are discussed. A model on the possible function of the nucleomorph hsp70 gene products is presented. PMID- 7874739 TI - Variability in genome organization of the zygomycete Parasitella parasitica. AB - In addition to conventional methods for the identification of fungi, molecular techniques at the DNA level are increasingly being employed. In order to check the validity of such experimental approaches, we have analyzed the well-defined species Parasitella parasitica, which belongs to the family Mucoraceae (Mucorales, Zygometes). The seven strains of this species, which are available from international strain collections, were analyzed by several molecular methods: restriction fragment length polymorphism analysis (RFLP), the random primer-dependent polymerase chain reaction (RAPD-PCR), and electrophoretic karyotyping. Unexpectedly, these strains are highly diverse at the molecular level. By these techniques they can be divided consistently into two different groups. Nevertheless, all seven strains belong to a single species. They show no morphological differences and sexual spores (zygospores) were found in all possible combinations either within or between the two groups. Southern-blot analysis of genomic DNA of all P. parasitica strains with RAPD-PCR-derived labelled probes shows the existence of repetitive elements characteristic for only one group of P. parasitica. In addition, chromosome sizes, which were separated by rotating-field electrophoresis, were highly divergent, and ranged from 3 to 6.5 Mb in one group and between 2 and 4.5 Mb in the other. The RAPD-PCR patterns also discriminate both groups of P. parasitica. However, they are very similar if strains of a single group are compared. Therefore, we propose that the determination of fungal species by molecular techniques should be vetted at least by morphological and physiological parameters and, whenever possible, by mating experiments. PMID- 7874740 TI - Disruption of the cyclosporin synthetase gene of Tolypocladium niveum. AB - Cyclosporin A is a potent and clinically-important immunosuppressive drug (SandimmunR). It is produced by the fungus Tolypocladium niveum. A transformation system for T. niveum ATCC34921 based on hygromycin selection was established. In order to obtain a T. niveum promoter, the cyclophilin gene was isolated using the Neurospora crassa gene as probe. A plasmid vector was constructed in which the promoter region of the T. niveum cyclophilin gene was fused to a bacterial hygromycin phosphotransferase gene. Protoplasts were transformed with this plasmid and hygromycin-resistant transformants were isolated. Using this transformation system, mutants of T. niveum with disrupted versions of the cyclosporin synthetase gene (simA) were engineered by DNA-mediated transformation. Disruption of the gene resulted in loss of the ability to produce cyclosporins. PMID- 7874741 TI - Heterologous and homologous plasmid integration at a spore-pigment locus in Penicillium paxilli generates large deletions. AB - Mutations in a spore pigmentation locus (brs; brown spore) in Penicillium paxilli were isolated at a relatively-high frequency (0.17%) following integrative transformation of the hygromycin-resistance plasmid pAN7-1. A molecular analysis of four independently-isolated Brs- mutants showed that all contained pAN7-1 integrated at a single-site that was unique for each mutant. A previously described Brs- mutant, YI-34 (Itoh et al. 1994), was a two-site integration. Three of the mutants had multiple copies of pAN7-1 arranged in head-to-tail tandem arrays. A 9.6-kb BamHI junction fragment was cloned from one of these, YI 33, by plasmid rescue and used to isolate two overlapping lambda clones, lambda WB33-1 and lambda WB33-2, that span about 30 kb in the region of the wild-type locus. When genomic digests of the five Brs- mutants were probed with these lambda clones all of them were found to contain an extensive deletion through a common region of the P. paxilli genome. Subsequent attempts to generate one-step gene replacements within a 4.5-kb EcoRI fragment at the wild-type locus resulted in the isolation of Brs- mutants at a frequency of 1.6%, but all mutants with this phenotype were also found to contain an extensive genomic deletion. Therefore, a common outcome of both heterologous and homologous plasmid integration at this locus is deletion formation. PMID- 7874742 TI - MRG1-1, a dominant allele that confers methomyl resistance in yeast expressing the cytoplasmic male sterility T-urf13 gene from maize. AB - We have previously described a eukaryotic heterologous expression system, with the urf13TW gene in yeast, which mimics the disease susceptibility associated with the Texas cytoplasmic male sterility in maize. This yeast model was used to isolate yeast nuclear mutants conferring methomyl resistance. The genetic strategy we have developed focused on screening for nuclear dominant yeast mutations which restore methomyl resistance. MRG1-1, a yeast nuclear dominant allele, was identified as a methomyl-resistance restorer. We have shown that methomyl resistance co-segregated with a pleiotropic phenotype in the heterozygous MRG1-1/MRG1 diploids, detectable even in the absence of the maize derived mitochondrial protein and/or methomyl. We observed an increase in oxygen uptake, a significant decrease of the levels of cytochrome aa3, and a decrease in the growth yield. This phenotype is influenced by the carbon source and the results suggest a defect in the adaptation to the respiratory pathway in MRG1-1 yeast cells. PMID- 7874743 TI - Characterization of genome plasticity in Ustilago hordei. AB - Southern-blot hybridization analysis was used to identify and quantify chromosome length polymorphisms for ten linkage groups of 14 races of Ustilago hordei. The bands identified by the probes were shown to vary as much as hundreds of kilobase pairs, but the magnitude of the variability was typically 5-15% of the average size of all bands to which a particular probe hybridized. A filamentous morphology mutant, recovered following heat-shock treatment of a strain with the greatest number of chromosome bands, was shown to have suffered a 50-kb deletion in a 940-kb chromosome. The mutation to filamentous morphology, designated fil1 1, and the deletion, were shown to invariably cosegregate 2:2 with the wild-type (sporidial) morphology in an ordered tetrad. Genetic and physical analyses place the Fil1 locus and the deletion near the terminus of one arm of the 940-kb chromosome. These results suggest that deletions of this type may be one of the causes of chromosome-length polymorphisms observed in field isolates of U. hordei. PMID- 7874744 TI - Expression of the large plastid gene, ORF2280, in tomato fruits and flowers. AB - The expression of ORF2280, a large plastid gene of unknown function, was examined in tomato leaves, in a developmental series of tomato fruits, and in tomato flowers. Western blots indicated that much more ORF2280 protein is present in fruits and flowers than in leaves. The most abundant proteins detected, 68 and 59 kDa, are present in about equal amounts in fruits of all stages; they are even more abundant in flowers. A 170-kDa ORF2280 protein is also present in fruit of all stages; it is most abundant in small green fruit. The presence of higher levels of ORF2280 proteins in tomato fruits and flowers indicates that it may have a specialized function in these nonphotosynthetic tissues. PMID- 7874745 TI - Analysis of the introns in genes encoding small G proteins. AB - Because all small G proteins (SGPs) possess a very similar array of structural and functional domains, they are obvious candidates for examining the relationships postulated to exist between the exon-intron structure of genes and the domain structure of the encoded proteins. To address this issue, and to possibly gain insight into the evolution of their introns, we have analyzed positions, sizes, and sequences of 125 introns from 28 SGP genes. These introns were found to be distributed in 60 different locations throughout the aligned sequences, with a preference for the 5'-half of the genes. More than 50% of the positions were found to be shared by two or more genes, and genes encoding SGPs of very similar amino acid sequence (i.e., isotypes) in quite closely related species tend to have most, or all, of their introns in identical locations, indicating a common evolutionary origin (homologous introns). However, with few exceptions, no statistically significant sequence similarity or common folding motif was found between homologous intron pairs. Only three intron positions are shared between members of distantly related SGP subfamilies. These three potentially ancient intron locations fall between regions encoding alpha-helices or beta-sheets, but two of them interrupt regions encoding known functional (guanosine-nucleotide-binding) modules. Intron positions that are occupied only in single genes, or in genes encoding very similar SGPs, do not show any preferential distribution with respect to regions encoding structural or functional motifs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874746 TI - Evolutionary variations in DNA sequences transferred from chloroplast genomes to mitochondrial genomes in the Gramineae. AB - The transfer of fragments of DNA from chloroplast genomes to mitochondrial genomes is considered to be a general phenomenon in higher plants. In the present study, Southern hybridization, together with amplification by PCR and DNA sequencing techniques, was used to examine the regions homologous to chloroplast rps19 in the mitochondrial genomes of several gramineous plants. In all the mitochondrial DNAs from the gramineous plants examined, except for that from wheat, the transferred fragments of chloroplast DNA were found to be maintained and the same junctions of mitochondrion-specific and chloroplast-like sequences were found at one terminus. This finding indicates that the transfer of the chloroplast sequence occurred in the distant past during the evolution of gramineous plants. Subsequent analysis revealed that the fragments had been variously rearranged among species with respect to the other terminus. Considering the current diversity of this one particular transferred fragment of chloroplast DNA, we propose that chloroplast-derived DNA sequences that have lost their original functions tend to be rearranged during evolution in mitochondrial genomes. PMID- 7874747 TI - A chromoplast-specific protein in Capsicum annuum: characterization and expression of the corresponding gene. AB - We have isolated cDNA and genomic clones corresponding to a gene highly and specifically expressed at the late stage of fruit-ripening in bell-pepper. Antibodies raised against the expressed protein allowed determination of the cellular localization of the gene product. The encoded protein is present only in chromoplasts from fully-ripe red fruits, as shown by Western analysis and import experiments. The corresponding mRNA accumulates to high levels during ripening at orange and red stages, but is not detected in yellow varieties impaired in the synthesis of ketocarotenoids. Several lines of evidence indicate that the encoded protein is an oxido-reductase involved in the synthesis of capsanthin and capsorubin. PMID- 7874748 TI - Isolation and characterization of a virus-resistant mutant of Cryphonectria parasitica. AB - Hypovirulent strain NB58 of Cryphonectria parasitica contains a dsRNA virus with a genome size of approximately 12.5 kb. Although NB58 is very stable in culture, a phenotypically-distinct sector arose which was found to be dsRNA-free. Attempts to infect the mutant strain, termed NB58F, by pairing with the parent strain (NB58) or other conversion-compatible, virus-containing strains have been unsuccessful. DNA fingerprint analysis showed that NB58, NB58F, and a representative dsRNA-free single-conidial isolate of NB58 termed NB58-19, were isogenic. The mutant culture was phenotypically stable, and all single-conidial progeny had the NB58F morphology. NB58F was intermediate between NB58 and NB58-19 in laccase production and virulence. Pigmentation and sporulation of NB58F, however, were reduced to near the level of NB58. In mating studies, NB58F functioned only as the male in sexual crosses. The mutant phenotype (F) predominated by a ratio of 5:2 among the ascospore progeny of F-type x wild-type crosses. These data suggest the lesion is nuclear and may be associated with a chromosomal abnormality. Attempts to infect the NB58F-type ascospore progeny failed, whereas the wild-type progeny were successfully infected with strains compatible with one or the other parent at a frequency of about 34%. Hyphal anastomosis and movement of cytoplasmic material occurred when NB58F was paired with a compatible strain, suggesting that the lesion is involved in viral maintenance as opposed to initial virus infection. NB58F represents the first virus-resistant isolate of C. parasitica to be described. PMID- 7874749 TI - Characterization of two minicircular plasmid-like DNAs isolated from date-palm mitochondria. AB - We report here the identification and characterization of two minicircular plasmid-like DNAs isolated from mitochondria of a moroccan date-palm variety. Both molecules were cloned and used as probes in Southern analyses of mitochondrial and total-cellular DNA. Evidence was obtained that these plasmid like DNAs cross-hybridized but did not show any homology to nuclear, chloroplastic, or main mitochondrial genomes. Sequence analysis revealed that both minicircles, 1,346- and 1,160-bp long, share several stretches of homology, the most important consisting of three identical clusters of lengths 42, 47 and 38 bp. In contrast, no major homology was observed with the other higher-plant plasmid-like DNAs reported so far. Sequence analysis also revealed the presence, in the same strand of one of the minicircles, of two open reading frames potentially encoding proteins 89 and 86 amino acids in length. Interestingly, Northern analyses, using single strands of each minicircle as probes, showed the presence of two transcripts hybridizing only with the strand bearing these two open reading frames. However, computer-assisted comparison of the predicted polypeptide sequences with a protein-sequence library failed to detect any significant homology to known sequences. PMID- 7874750 TI - Frequent site-specific mit- deletions at cryptic exon-intron junctions in the COX1 gene of yeast mtDNA. AB - A class of large site-specific deletions (del-B) occurs with exceptionally-high frequencies of 10(-3) in the mitochondrial COX1 gene of Mn(2+)-treated yeast cells. This work shows that del-B deletions are associated with COX1 intron aI1. All five deletion mutants studied have their upstream end at the authentic 3' splice site of this intron. The deletion ends 8.2 kb downstream in intron aI5b. This downstream deletion-end constitutes a potentially-cryptic 5' splice site for intron aI1. The coincidences of the del-B deletion-ends with authentic and cryptic RNA splice sites suggest that the group-II intron aI1, and/or the RNA maturase encoded in it, plays an active role in this exceptionally-frequent, site specific deletion process. PMID- 7874752 TI - Physical mapping of the Schizosaccharomyces pombe histone genes. AB - The histone-encoding genes in Schizosaccharomyces pombe were physically mapped by hybridisation to filters containing cosmid and P1 genomic libraries. The H2A.2 gene and the H2A.1-H2B.1 gene pair mapped between the ade6 and rikI genes on chromosome III. The three H4-H3 gene pairs were mapped to three different regions by a H4.1 probe. Southern analysis of clones from each region revealed the positions of the three H4-H3 gene pairs. H4.1-H3.1 was localised to chromosome I between the mei2 and rad1 genes; H4.2-H3.2 mapped between rad3 and cdc2 on chromosome II; H4.3-H3.3 was localised to a region between the nuc1 and puc1 genes on chromosome II. PMID- 7874751 TI - Sequence analysis of three deficient mutants of cytochrome oxidase subunit I of Saccharomyces cerevisiae and their revertants. AB - Three respiratory-deficient mutants of cytochrome oxidase subunit I in the yeast mitochondrion have been sequenced. They are located in, or near, transmembrane segment VI, the catalytic core of the enzyme. Respiratory-competent revertants have been selected and studied. The mutant V244M was found to revert at the same site in valine (wild-type), isoleucine or threonine. The revertants of the mutant G251R were of three types: glycine (wild-type), serine and threonine at position 251. A search for second-site mutations was carried out but none were found. Among 60 revertants tested, the mutant K265M was found to revert only to the wild type allele. PMID- 7874755 TI - [Tumor markers: recent advances and its future trends]. PMID- 7874754 TI - Molecular characterisation of GTP1, a Saccharomyces cerevisiae gene encoding a small GTP-binding protein. AB - DNA sequence analysis upstream of the yeast DNA repair gene SNM1 revealed gene GTP1 with an ORF of 573 bp on chromosome XIII. The putative amino-acid sequence of the encoded protein shows homology to proteins of the ARF-class of small GTP binding proteins. Homology within GTP-binding motifs is highly conserved. Gene disruption showed that GTP1 is not an essential gene and that it has no influence on the expression of the DNA repair gene SNM1 with which it shares a 191-bp promoter region. PMID- 7874753 TI - Structure and expression characteristics of the chloroplast DNA region containing the split gene for tRNA(Gly) (UCC) from mustard (Sinapis alba L.). AB - The mustard chloroplast gene trnG-UCC is split by a 717-bp group-II intron. Northern hybridization and RNase protection experiments suggest cotranscription with the upstream psbK-psbI operon, but not with the downstream trnR-UCU gene. The ends of most RNase-protected fragments between psbI and trnG correlate with the position of two potential stem-loop structures in this region, which could act as RNA processing elements. However, one RNA 5' end, approximately 75 bp upstream of the trnG 5' exon, does not so correlate and is preceded by prokaryotic-type '-10' and '-35' sequence elements. This suggests the possibility that a fraction of the trnG transcripts is initiated here. All precursor transcripts spanning the trnG region seem to have a common 3' end, which was located 117 bp downstream from the 3' exon, immediately after a stem-loop region. During seedling development, the major 0.8-0.9-kb trnG precursor transcripts show a transient maximum level at around 48 h after sowing, at a time when the mature tRNA begins to accumulate to constant levels. No significant differences in transcript patterns were observed either in the light or in darkness. PMID- 7874756 TI - [An immunohistochemical study of Ki-67 expression of brain tumor cells and mononuclear cell subsets infiltrating these tumors]. AB - Fifty-one brain tumors were studied by immunohistochemical methods. The densities of CD45RO+, CD4(OPD4) and CD8 T cells infiltrating the tumors showed negative correlation with the tumor size and positive correlation with the density of macrophages. The density of Ki-67+ tumor cells rose along with the increase in tumor malignancy and showed positive correlation with the tumor size and negative correlation with the density of CD4 T cells. The CD4/CD8 ratio was 0.853, far lower than the normal ratio and there was also positive correlation between their densities. The above results suggest that the level of Ki-67 expression can objectively reflect the proliferative rate and malignant grade of brain tumors. The CD45RO+, CD4 and CD8 T cells infiltrating brain tumors are able to directly inhibit tumor growth. The macrophages take part indirectly in the immunoresponse against brain tumors by influencing CD4 and CD8 T cells. Brain tumors may inhibit the proliferation and immune function of the CD4 subset. PMID- 7874757 TI - [Gene diagnosis of pancreatic adenocarcinoma]. AB - Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to analyze c-Ki-ras codon 12 mutation in 27 fine needle aspiration biopsy (FNAB) specimens of the pancreas and its adjacent organs for the diagnosis of pancreatic adenocarcinoma. C-Ki-ras codon 12 mutation was present in 14 out of 15 cases of pancreatic adenocarcinoma, the positive rate was 93.33% (14/15); whereas no mutation was detected in those obtained from 12 patients with chronic pancreatitis, pancreatic cyst, gallbladder carcinoma, carcinoma of ampulla of Vater and gastric lymphoma. The results of this study verifies the PCR-RFLP technique as a practical, sensitive, rapid and reliable method for the detection of c-Ki-ras codon 12 mutation in the diagnosis of pancreatic adenocarcinoma. PMID- 7874758 TI - [The expression of PCNA and EGF gamma in tumor cells of experimental hepatocellular carcinoma of liver and squamous cell carcinoma of stomach in rats]. AB - The expression of PCNA and EGF gamma in chemically induced hepatocellular carcinoma and squamous cell carcinoma cells from rats were observed with immunohistochemical techniques. The results showed that the carcinoma cells of both tumors revealed a positive immunoreaction to both factors. According to the amount of MC surrounding the tumor cell nests, the specimens could be divided into two groups: the group with abundant MC infiltration and the group with little or no MC infiltration. The PCNA positive cells in carcinoma cell nests of both groups were calculated respectively. It revealed that the amount of PCNA positive cells in the group with little or no MC was significantly more than that in the other group. The ratio between the 2 groups in liver carcinoma was approximately 3:1 and in stomach cancer it was 2:1. An overexpression of EGF gamma was observed in tumor tissues of both groups, but the amount of EGF gamma positive cells in the group with little or no MC was much higher than that of the group with abundant MC. PMID- 7874759 TI - [The relation between integrin, type IV collagenase and extracellular matrix in invasion and metastasis of gastric carcinoma]. AB - The expression of integrin Alpha-6-subunit, laminin, type IV collagenase, type IV collagen and ras p21 were studied immunohistochemically in gastric cancer. The results showed that the expression of alpha 6 and laminin (LN) was often in continuous or interrupted linear pattern in the expanding type of gastric carcinoma (GC); while in the infiltrating type of GC, they were expressed either in interrupted spotty or fragmentary pattern, or almost lost. Suggesting that the interaction between the laminin receptor and its ligand may influence the mode of growth in GC. Intense expression of type IV collagenase was often found in GC cells, especially in the infiltrative type of GC and in those with lymph node metastasis, it can therefore be used as a marker for invasion and metastasis of GC cells. A positive correlation was found between the expression of type IV collagenase and ras p21 in GC. The expression of type IV collagen was similar to that of laminin, but in reverse proportion to the expression of type IV collagenase. These investigations provide a better understanding of the molecular pathological basis of tumor invasion and metastasis. PMID- 7874760 TI - [Comparative study of the expression of IGF-2 and HBxAg in human hepatocellular carcinoma and liver cirrhosis]. AB - 60 Cases of hepatocellular carcinoma (HCC) and 47 cases of liver cirrhosis (LC) were examined with immunocytochemistry methods using antibodies against IGF-2 and HBxAg on paraffin embedded sections. 32 HCC and 37 LC were found to be positive to HBxAg, in which the positive rates of IGF-2 were 100% (32/32) and 94.6% (35/37) respectively. 28 HCC and 10 LC were found to be HBxAg negative, IGF-2 was positive in 23 HCC (82.1%) and 6 LC (60%). The positive expression rates of IGF-2 in the HBxAg positive tissues were significantly higher than those in the HBxAg negative tissues (P < 0.05). There were three types of IGF-2 distribution in HCC and LC: (1) perinucleus; (2) diffuse in cytoplasm; (3) in nucleus. Small polygonal liver cells (SPLC) were found in the liver tissue surrounding the tumor or cirrhosis, the SPLC were positive to both IGF-2 and HBxAg. The positive rates of IGF-2 in SPLC were 86.4% (38/44) in HBxAg positive group and 40.5% (15/37) in the HBxAg negative group. The above findings suggest that IGF-2 plays an important role in abnormal proliferation of HCC and SPLC. The relation of IGF-2 and HBxAg and the nature of SPLC were also discussed. PMID- 7874761 TI - [Observations on the relation of gastric carcinoma to Epstein-Barr virus]. AB - Epstein-Barr virus (EBV) has been detected in the tumor cells of some cases of gastric carcinoma. The monoclonal expansion of EBV contained in tumor cells and increased serum antibody titers suggest that gastric carcinoma may be associated with EBV infection. It has been known for many years that EBV is associated with nasopharyngeal carcinoma which has a high incidence rate in China. The relation of EBV infection to gastric carcinoma is not clear. 110 cases of gastric carcinoma of Chinese patients were studied by use of EBV encoded small RNA (EBER 1) in situ hybridization. EBV was detected in 3 of the 49 cases (6.1%) from Shenyang in north China and 1 of the 61 cases (1.6%) from Changsha in south China. The EBV positive rate in gastric carcinoma of Chinese is not as high as it is in Americans and Japanese. PMID- 7874762 TI - [An immunohistochemical study on megakaryocytes in patients with myelodysplastic syndromes]. AB - An immunohistochemical study was performed on trephine biopsy specimens of bone marrow in 10 patients with myelodysplastic syndromes (MDS). Monoclonal antibodies HIP7 and CDW41 were used against platelet glycoprotein IIb/IIIa (CD41) to determine dysmegakaryopoiesis including its size, proportion of micromegakaryocytes, location and staining characteristics. The results show that the dysmegakaryopoiesis of MDS includes the increased number and high proportion of micromegakaryocytes, the altered architectural distribution and the considerable variation in staining. These may be helpful in the diagnosis and differential diagnosis of MDS. PMID- 7874763 TI - [Autopsy analysis of 90 workers exposed to workplace dusts]. AB - An analysis of 90 autopsy cases of workers exposed to workplace dusts showed that the older they were the higher the positive rate of pneumoconiosis and the more serious the pathological changes in the lungs. All the cases over 65 years of age were diagnosed with pneumoconiosis. The positive rate of pneumoconiosis diagnosed by pathology was associated with the duration of exposure to workplace dusts. The positive rate was 67.92% in cases exposed to workplace dusts for over 10 years and 93.3% in those exposed for over 30 years. 63.3% of all the autopsy cases reported here were given the diagnosis of pneumoconiosis after pathological examination, whereas only 13.3% were diagnosed clinically before they died. These data demonstrate the importance of autopsy in the diagnosis of pneumoconiosis. PMID- 7874764 TI - [Induction of gastric adenocarcinoma in Wistar rats following neonatal exposure to MNNG and neoplastic transformation assay of DNA of the induced cancer]. AB - Adenocarcinoma, adenoma and dysplasia of the stomach of adult Wistar rats were induced following administration of MNNG for 10 days by gavage when they were new born. The incidence of the three types of pathological lesions at the dose of 0.4 mg MNNG per rat being 39%, 50% and 100% respectively. Induction of gastric adenocarcinoma is dose-dependent. The incidence of adenocarcinoma in male rats being significantly higher then that of female rats (P < 0.02). 23 of 33 (70%) induced cancers were found in the gastric antrum. By the use of DNA cotransfection technique and the assay of carcinogenicity in the Balb/c nude mice, it was also found that the DNA of 4 of the 6 induced gastric carcinomas could transform NIH/3T3 cells into malignant cells, an indication that the induced cancer DNA contains transforming gene. PMID- 7874765 TI - [A study on the mechanism of invasion of colorectal mucinous adenocarcinoma]. AB - Statistics from a 64 case study showed that mucinous adenocarcinoma was apt to invade the intestinal wall and to metastasize to lymph nodes (P < 0.05). The activity of arylsulfatase and lysozyme of mucinous adenocarcinoma was stronger than that of the papillary and tubular adenocarcinoma (P < 0.05). In RR staining for electron microscopic observation, a significant decrease of proteoglycan granules was found in the surrounding matrix of mucinous adenocarcinoma, which correlated with the amount of arylsulfatase and lysozyme secreted by mucinous adenocarcinoma. These enzymes reduced the degree of sulfation in heparan sulfate and degraded proteoglycans. The proteoglycan structural barrier having been destroyed, facilitates mucinous adenocarcinoma to infiltrate and metastasize. PMID- 7874766 TI - [A study of human papillary virus infection by in situ hybridization and histopathology in squamous cell carcinoma of the lung]. AB - Paraffin embedded archival tissue from 7/49 carcinomas of the lung which were positive for HPV DNA examined by multiple PCR were again searched for HPV DNA by in situ hybridization technique. Five cases were found positive for HPV DNA by in situ hybridization, of which three cases were positive for HPV 11, One was positive for HPV 16 and the other was positive for both HPV 11 and 16. The hybridization signal was mainly located in the nuclei of the koilocytotic tumor cells. These results suggest that HPV infection may have some role in the development of squamous cell carcinoma of the lung. PMID- 7874767 TI - [P21 expression of ras oncogene product in benign and malignant female mammary lesions]. AB - The level of P21 protein in 40 breast carcinomas, 37 benign tumors and 52 proliferative breast diseases in females were determined by the ABC immunohistochemical method. The positive rate was 72.5%, 32.43% and 23.07% respectively. The positive expressions were mainly found in tumor cells in poorly differentiated infiltrating ductal carcinomas and in 3 of the 5 proliferative breast disease cases with atypical hyperplasia of ductal epithelium, suggesting that P21 protein detection could provide a molecular biological basis for the evaluation of malignant changes and the prognosis of mammary lesions. PMID- 7874768 TI - Glycemic control: perhaps we can define it, but can we measure it? PMID- 7874769 TI - Improved PCR amplification/Hhal restriction for unambiguous determination of apolipoprotein E alleles. AB - We present a modification to the polymerase chain reaction amplification/Hhal restriction isotyping method for human apolipoprotein (apo) E. This method includes a mutagenic forward primer and 5'-end labeling of both primers. These modifications of the original method described by Hixon and Vernier (J Lipid Res 1990;31:545-8) allow sensitive and unambiguous determination of apoE genotypes. PMID- 7874770 TI - Three assays for glycohemoglobin compared. AB - Using 123 specimens, we compared the concordance of three different methods for determining glycohemoglobin (GHb): the Diamat (Bio-Rad Laboratories), an automated analyzer measuring HbA1c by cation-exchange chromatography; an assay with the IMx analyzer (Abbott Laboratories), based on boronate affinity binding; and an HPLC method measuring HbA1c by cation-exchange chromatography on a PolyCAT A column (PolyLC Inc.). The Pearson's correlation coefficient between PolyCAT A and Diamat was 0.900 +/- 0.038 (mean +/- 2 SD) and between PolyCAT A and IMx, 0.857 +/- 0.042. However, up to twofold differences were seen in some samples. The proportion of GHb was consistently lower with the PolyCAT A method than with the other two assays, apparently because of better separation of HbA1c from nonglycated coeluting forms of Hb. The difference in glycation percentage between the PolyCAT A and Diamat methods is 2-3% over the whole concentration range. These results point to the limitations of Diamat as a reference method to be used to calibrate other methods for determining HbA1c. Further, a switch from one method to another is likely to cause considerable problems in the clinical follow up of certain patients. PMID- 7874771 TI - Two bone alkaline phosphatase assays compared with osteocalcin as a marker of bone formation in healthy elderly women. AB - Serum bone alkaline phosphatase (ALP; EC 3.1.3.1) was measured with a wheat germ agglutinin (WGA) precipitation assay and with a new IRMA in a group of healthy elderly women. Both assays were correlated with serum total ALP activity and with osteocalcin. The two bone ALP assays have comparable within- and between-run imprecisions (WGA assay within-run CVs 2.6-5.4% and between-run, 4.0-5.1%; IRMA within-run CV 5.0% and between-run, 3.2%). Comparison of the WGA precipitation assay (x) with the IRMA (y) demonstrated a correlation coefficient of 0.87 [Deming regression equation: y = (0.58 +/- 0.02)x - (4.62 +/- 0.45); n = 101; Sy/x = 1.26; P < 0.001). Correlation studies with osteocalcin and total ALP showed correlation coefficients (all P < 0.001) of 0.34 and 0.65, respectively, for the WGA precipitation assay and of 0.36 and 0.68, respectively, for the IRMA. We conclude that the two bone ALP assays have similar imprecision and that neither can be given preference over the other as a marker of bone turnover. PMID- 7874772 TI - Prostatic acid phosphatase assay with self-indicating substrate 2,6-dichloro-4 acetylphenyl phosphate. AB - We characterized six self-indicating substrates, synthesized as the derivative compounds of acetylphenyl phosphate, for serum prostatic acid phosphatase (PAP) activity. One of the substrates, 2,6-dichloro-4-acetylphenyl phosphate (DCAPP), is superior to others in terms of stability, affinity, and low Km for PAP. The hydrolyzed product, 2,6-dichloro-4-acetylphenol (DCAP), has a maximum absorption at 334.2 nm, a pKa of 4.15, and a molar absorptivity at 340 nm of 21,490 L.mol 1.cm-1 in citrate-HCl buffer, pH 5.4. PAP activity was assessed by subtracting tartaric acid-inhibited acid phosphatase activity from total acid phosphatase activity. Our assay system involving DCAPP is a unique kinetic method that shows good reproducibility, wide analytical dynamic range, and high specificity for PAP. Moreover, it is easily adaptable to automated analyzers because the product, DCAP, can be monitored at 340 nm. PMID- 7874773 TI - Analytical and clinical performance of improved Abbott IMx CA 125 assay: comparison with Abbott CA 125 RIA. AB - We compared the improved Abbott IMx cancer antigen (CA) 125 assay (cat. no. 7A89) with the Abbott CA 125 RIA. Serum specimens were from healthy perimenopausal women (n = 124) and from patients with benign gynecologic and nongynecologic diseases (n = 124), ovarian carcinoma (n = 104), or other malignancies (n = 193). The IMx assay detected as little as 0.193 kAU/L CA 125 (AU = arbitrary Abbott unit), demonstrated up to 29% overestimation upon serum dilution, low within assay (2.7-5.6%) and between-assay (4.8-8.2%) CVs, and no high-dose hook effect < or = 46,000 kAU/L nor influence from human anti-mouse antibodies in serum of women injected with OC 125 F(ab')2. Values by IMx were 20% lower than by RIA for healthy perimenopausal women (n = 100; IMx = 0.80 RIA - 2.5 kAU/L), and at least 50% higher for those with benign or malignant ovarian disorders at concentrations < 100 kAU/L. Receiver-operating characteristic (ROC) curve analysis of ovarian neoplasma vs perimenopausal controls indicated a gain of specificity and sensitivity with the improved IMx assay over the RIA, but ROC performance was the same with either assay if patients with benign ovarian disorders were used as controls. PMID- 7874774 TI - Coenzyme Q: potentially useful index of bioenergetic and oxidative status of spermatozoa. AB - The concentration of coenzyme Q10 (CoQ10), a key intermediate of the mitochondrial respiratory chain, was determined in spermatozoa of 13 fertile subjects, 8 potentially fertile patients, and 12 infertile patients. CoQ10 concentrations were significantly higher (P < 0.001) in infertile patients than in fertile and potentially fertile subjects. The difference between potentially fertile and fertile subjects was also significant (P < 0.001). We propose that a decrease in consumption of CoQ10 in both infertile and potentially fertile populations is due to an autoregulatory mechanism of ATP production. PMID- 7874775 TI - Susceptibility of plasma to ferrous iron/hydrogen peroxide-mediated oxidation: demonstration of a possible Fenton reaction. AB - The aim of our study was to evaluate a model system by using iron in the peroxidation of plasma. Lipid peroxidation was monitored by fluorometric measurement of lipid peroxides (LPO). Plasma coincubated with Fe2+ and H2O2 had a 268% increase in plasma LPO after 1 h. The optimum concentrations were 0.42 mmol/L Fe2+ and 0.73 mol/L H2O2. Coincubation of plasma with these concentrations of Fe2+ and H2O2 separately resulted in no increase in plasma LPO. The increase in plasma LPO after oxidation with Fe2+/H2O2 was paralleled by a decrease in plasma polyunsaturated fatty acids, an increase in the relative electrophoretic mobility of low-density lipoprotein (LDL), and decreases in apolipoprotein (apo) B-100 and apo A-I immunoreactivity. In vitro oxidation of LDL and high-density lipoprotein separately with this system produced increases of LPO of 246% and 128%, respectively. LPO formation in plasma was inhibited by catalase, desferrioxamine, and mannitol, but not by superoxide dismutase. Hydroxyl radical generation with Fe2+/H2O2 was evidenced by fragmentation of deoxyribose. We conclude that the Fe2+/H2O2 system, possibly by a Fenton reaction mechanism, resulted in significant plasma oxidation. This model system may be useful for examining lipid peroxidation in clinical investigations. PMID- 7874776 TI - Changes in serum lipoprotein(a) and lipids during treatment of hyperthyroidism. AB - Because of suggestions that thyroid hormones modulate serum lipoprotein(a) [Lp(a)] concentration, we evaluated prospectively the serial changes of serum Lp(a), measured as apolipoprotein(a) [apo(a)], and other lipoproteins in 40 subjects with hyperthyroidism treated with radioactive iodine (RAI) therapy. Hyperthyroid patients had lower (P < 0.001) concentrations of apo(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apo B, but higher apo A-I concentrations compared with age-matched controls [geometric mean (range)]; apo(a) 81 (17-614) vs 187 (17-1808 IU/L): TC 4.07 +/- 0.8 vs 5.22 +/- 1.00 mmol/L (mean +/- SD); LDL C 2.47 +/- 0.89 vs 3.40 +/- 0.88 mmol/L; HDL-C 1.05 +/- 0.33 vs 1.24 +/- 0.34 mmol/L; apo B 0.66 +/- 0.23 vs 1.13 +/- 0.34 g/L, and apo A-I 2.07 +/- 0.42 vs 1.46 +/- 0.28 g/L, respectively. Euthyroidism was associated with normalization of serum TC, LDL-C, and apo B within 1 month of treatment. However, apo(a) required 4 months to normalize, and HDL-C and apo A-I were still abnormal 6 months after RAI. Serum apo(a), TC, LDL-C, and apo B were negatively correlated with serum thyroxine (T4), free thyroxine index, and triiodothyronine (T3) and positively correlated with thyrotropin during the transitional period from hyperthyroidism to euthyroidism. Parallel changes of these lipoproteins and thyroid hormones were also observed after treatment of hyperthyroidism. In conclusion, thyroid hormones do modulate lipoproteins, particularly Lp(a). The delay in normalization of apo(a) but not LDL suggests an effect on apo(a) production rather than on LDL removal. PMID- 7874777 TI - Immunoseparation method for measuring low-density lipoprotein cholesterol directly from serum evaluated. AB - Low-density lipoprotein (LDL) cholesterol can not be calculated from other lipid measurements when samples are obtained from nonfasting individuals or when triglycerides are > or = 4.0 g/L. We have evaluated a direct LDL cholesterol assay for analyzing 115 fresh serum samples obtained from fasting and nonfasting dyslipidemic patients with triglycerides < or = 35.85 g/L, who were receiving diet and (or) drug treatments. Results were highly correlated with those by ultracentrifugation (r = 0.97), with a mean/median bias of -2.9%/0.7% ( 0.001/0.010 g/L) and an absolute bias of 9.5%/6.4% (0.119/0.090 g/L). The assay correctly classified LDL cholesterol concentrations < 1.30 g/L 81% of the time, 1.30-1.60 g/L 76% of the time, and > or = 1.60 g/L 94% of the time. Precision studies provided within- and between-run CVs in the range of 1.2-3.8% and 2.0 5.1%, respectively. Our data indicate that this assay is an accurate method for measuring LDLC directly from fresh serum obtained from fasting or nonfasting subjects with a wide range of triglyceride values. PMID- 7874778 TI - Lipoprotein(a) in childhood: relation with other atherosclerosis risk factors and family history of atherosclerosis. AB - The relation between lipoprotein(a) [Lp(a)], apolipoprotein (apo) E phenotypes, cholesterol, triglycerides, apo A-I, apo B, and a family history of atherosclerosis or risk factors was studied in 2- and 4-year-old French Caucasian children (n = 499). Lp(a) concentrations were distributed in a typical skewed manner and were found to be an independent lipid variable. The distribution of apo E phenotypes did not differ by gender. Cholesterol and apo B were under apo E phenotype control; Lp(a) was not. A significant positive relation was found between Lp(a) concentrations and the number of parental risk factors. Children whose grandparents had a history of cardiovascular disease had Lp(a) concentrations shifted towards higher values. Measurement of Lp(a) in children may help to identify those at an increased risk of atherosclerotic disease, especially when their parents have at least two relevant risk factors. PMID- 7874779 TI - External quality assessment in clinical neurochemistry: survey of analysis for cerebrospinal fluid (CSF) proteins based on CSF/serum quotients. AB - Participants (230) from Germany and 20 laboratories in 11 European countries took part in a newly designed cerebrospinal fluid (CSF) survey distributed by INSTAND. Conventional proficiency testing for albumin, IgG, IgA, and IgM in CSF and serum, for total protein in CSF, and for oligoclonal IgG in CSF and serum was combined with evaluation and interpretation of CSF/serum quotients in quotient diagrams. The correct detection of a blood-CSF barrier dysfunction and the pattern of intrathecal immunoglobulin synthesis was judged. The accuracy of CSF/serum quotients and their clinically relevant interpretation was given first priority as a new concept in quality assessment. The main result of the surveys was to confirm that CSF/serum quotients of proteins represent method-independent values approaching the quality of reference values. This finding has consequences for internal quality control of CSF analysis and for accreditation bodies. The sensitivity of the methods for quantifying IgA and IgM in CSF and for detecting oligoclonal IgG fractions is discussed. PMID- 7874780 TI - Laboratory methods and quality assurance in the Cardiovascular Health Study. AB - The Cardiovascular Health Study is an observational cohort study of risk factors for cardiovascular disease in 5201 participants, ages > or = 65 years. We report the methods and quality-assurance results for blood procurement, processing, shipping, storage, and sample analysis used during the first examination period (May 1989-June 1990). The most frequent difficulty in phlebotomy and processing was the requirement of more than one venipuncture (in 2.6% of the participants). The CVs for control materials ranged from 0.93% for glucose to 10.7% for insulin; most were < 4%. In addition to standard quality-assurance methods, we applied two other methods: technical error calculation for replicates, and weighted linear regression to assess time trend in results of control materials. After outliers were excluded, technical error values ranged from 1.7 for uric acid to 18.8 for insulin. Factor VII and factor VIII had slight trends over the 12-month analysis period. Results of quality-assurance analyses used to resolve problems were successful, thereby improving the second laboratory examination. PMID- 7874781 TI - Role of a central laboratory in implementing national cholesterol education panel guidelines in rural practices: model system for managed care. AB - We describe the use of a central laboratory to identify patients who may be candidates for a hypercholesterolemia treatment program and to direct their referral into this program. The laboratory, providing service for 16 medical practices in a rural area of upstate New York, served as the entry point to the treatment program for those patients with serum cholesterol > or = 5.18 mmol/L. This treatment program, designed to follow the National Cholesterol Education Program Adult Treatment Panel Guidelines, was provided by the lipid referral center staff, including a registered dietitian and a lipid specialist. After introduction of this program, 52% of eligible patients received nutritional counseling for hypercholesterolemia, compared with only 29% in usual care settings. This program represents an enhanced role for laboratories in the implementation of treatment protocols typical of those adopted by managed care networks. PMID- 7874782 TI - Essential and toxic element concentrations in fresh and formalin-fixed human autopsy tissues. AB - The concentrations of five essential elements and six potentially toxic elements were determined in seven organs collected at autopsy from 30 human subjects. Elemental analyses were carried out by graphite furnace atomic absorption spectroscopy, and inductively coupled plasma emission spectroscopy, and inductively coupled plasma mass spectroscopy, and concentrations in fresh and formalin-fixed tissues were compared. Formalin-fixation long-term storage has little effect on most element concentrations in tissue, except for Al and Mn, which changed with prolonged storage in formalin. The kidney and liver contained the greatest concentrations of toxic elements compared with other organs, whereas the essential elements were uniformly distributed among all organs. There was no more than a 10-fold difference in the tissue concentration of the elements studied among the organs, except for the concentration of Fe in liver, and Ca and Mg in bone. We also demonstrate that these elements are homogeneously distributed in tissues. PMID- 7874783 TI - Pharmacodynamic assessment of mycophenolic acid-induced immunosuppression by measuring IMP dehydrogenase activity. AB - Pharmacodynamic monitoring of the biological effect of immunosuppressive drugs provides an alternative to traditional therapeutic drug monitoring. We chose this method to investigate mycophenolic acid (MPA), an immunosuppressive drug that mediates its effect by inhibition of IMP dehydrogenase (IMPDH), a key enzyme in the de novo biosynthesis of purines. Using an assay developed for measuring IMPDH activity in whole blood, we found the concentration of MPA required for 50% inhibition of enzyme activity to be in the range of 2.0-5.0 mg/L for both human and rabbit blood. The amount of enzyme activity in whole blood depended on the concentration of the leukocytes, was unaffected by the type of anticoagulant used, and was stable in blood specimens stored for as long as 48 h at 4 degrees C. An inverse relationship was found between plasma MPA concentrations and IMPDH activity in rabbits administered a single dose of RS-61443, the prodrug of MPA. Maximal inhibition of IMPDH activity (by approximately 60%) occurs at peak concentrations of MPA; as the concentration of the drug decreases postdose, the enzyme activity gradually increases with little or no inhibition being observed 24 h postdose. PMID- 7874784 TI - Simultaneous determination of alcohols and ethylene glycol in serum by packed- or capillary-column gas chromatography. AB - We developed a packed-column chromatographic procedure capable of simultaneous quantitation of methanol, ethanol, isopropanol, acetone, and ethylene glycol. This method was then updated to a rapid, sensitive, wide-bore capillary method. The packed-column system uses direct injection of 1 microL of Na2WO4/H2SO4 deproteinized serum onto a 1.8 m x 2 mm (i.d.) column packed with 80/100 HayeSep R. A linear temperature gradient from 90 to 205 degrees C allows complete elution of all components within 20 min; minimum detection limits are 2 mmol/L. The wide bore capillary method uses 0.1 microL of sample deproteinized by ultrafiltration, injected onto a 30 m x 0.53 mm (i.d.) 3-microns Rtx-200 (Restek) column. Baseline resolution to a minimum detection limit of 0.1 mmol/L of all compounds is achieved in 5 min with a linear temperature gradient from 40 to 250 degrees C and dual internal standards of n-propanol and 1,2-butanediol. PMID- 7874785 TI - Analytical artifacts in hematocrit measurements by whole-blood chemistry analyzers. AB - Compact analyzers suited to near-patient testing estimate hematocrit by measuring the conductivity of undiluted blood. We evaluated the accuracy of hematocrit determination of one such analyzer (Instrumentation Laboratory BGE analyzer) against an automated cell counter (EPC) and packed cell volume (PCV) microhematocrit. When specimens (n = 34) from outpatient and ward patients were analyzed with all three methods, the BGE analyzer correlated well with both EPC and PCV hematocrit determinations (BGE = 1.00 PCV + 0.3%, S(y)/x = 2.0%), suggesting that all three methods are similar in performance for most patients. However, a patient with increased plasma osmolality showed significant decreases in BGE and PCV hematocrits relative to the EPC method. The differences in hematocrit measurements could be reproduced by adding solutes to blood in vitro or by modifying the plasma osmolality of rats in vivo. Samples from patients undergoing cardiac surgery, whose blood had large changes in protein concentration, showed discrepancies between hematocrits by conductivity and other methods; similar effects could be produced by changes in protein concentration or in vitro addition of polyethylene glycol. We conclude that conductivity measurements provide accurate hematocrit results for physiologically normal subjects but not for some intensive-care and surgical patients. PMID- 7874786 TI - Discordance between results for serum troponin T and troponin I in renal disease. AB - Two patients were investigated for unexplained increases in troponin T. In the first patient, who had rhabdomyolysis and acute renal failure, troponin T reached a peak value of 13.50 micrograms/L (67.5-fold the upper reference limit). The second patient had chronic renal failure and the troponin T peak value was 2.85 micrograms/L (14.3-fold the upper reference limit). Clinical investigations indicated no evidence of myocardial damage. Serum or plasma specimens were analyzed for total creatine kinase (CK), CK-2 mass, CK-2 isoform ratio, myoglobin, troponin T, troponin I, and myosin light chains; all except troponin I were at above-normal concentrations. We also investigated six additional renal patients with above-normal troponin T; troponin I was slightly increased in only one of these six patients. Our findings demonstrate discordance between results for troponin T and troponin I in renal patients. PMID- 7874787 TI - Apparent instability of osteocalcin in serum as measured with different commercially available immunoassays. PMID- 7874788 TI - Subtyping hepatitis C virus. PMID- 7874789 TI - Rapid ultrafiltration method for detecting myoglobinuria. PMID- 7874790 TI - PCR analysis of hair root specimens to detect Tay-Sachs disease carriers in Ashkenazi Jews. PMID- 7874791 TI - Unusual case of suspected acute porphyria. PMID- 7874792 TI - Comparing assays of antibodies to modified low-density lipoproteins. PMID- 7874793 TI - Modification of NCCLS EP10 to include interference screening. PMID- 7874794 TI - Circadian rhythms of lipoproteins. PMID- 7874795 TI - Effects of blended lithium-zinc heparin on ionized calcium and general clinical chemistry tests. PMID- 7874796 TI - Appropriate excitation/emission wavelengths for fluorometric determination of thiobarbituric acid-reactive substances. PMID- 7874797 TI - Two capillary blood-collection techniques for estimating glycohemoglobin compared. PMID- 7874798 TI - Importance of using molar concentrations to express cross-reactivity in immunoassays. PMID- 7874799 TI - The role of SPECT imaging in pediatric renal transplants. AB - Post-transplant hypertension can be a diagnostic dilemma. In a select population of pediatric patients, in whom other diagnostic methods failed to reveal an abnormality, renal cortical SPECT imaging, using either Tc-99m GH or Tc-99m DMSA, revealed information that was not apparent on conventional planar renal scintigraphy. Abnormalities detected by this methodology included unsuspected renal infarct and areas of segmental perfusion deficit. The authors conclude that this methodology is a valuable tool in the evaluation of post renal transplantation hypertension in pediatric patients. PMID- 7874800 TI - Background correction in estimating initial renal uptake. Comparison between Tc 99m MAG3 and Tc-99m DTPA. AB - A gamma camera method with no blood sampling assesses differential renal function based on initial renal uptake, and requires background correction. The effect of background correction on estimates of initial renal uptake was compared on renograms using Tc-99m MAG3 and Tc-99m DTPA renographies in 14 patients. Renal counts for 2-3 minutes were obtained using three sets of regions of interest (ROIs): rectangular renal and subrenal background ROIs, rectangular renal and perirenal background ROIs, and hand-drawn renal and subrenal background ROIs. Correlations between estimates of initial renal uptake by the three methods were higher for Tc-99m MAG3 renography than for Tc-99m DTPA imaging, suggesting higher reproducibility in evaluating differential renal function using Tc-99m MAG3 renography and a gamma camera method. Although the ratio of counts in the suprarenal area to those in the subrenal area was significantly higher for the right side in the Tc-99m MAG3 study, probably because of hepatic activity, the relative uptake in the right kidney for Tc-99m MAG3 did not differ from that for Tc-99m DTPA. Initial uptake of Tc-99m MAG3 was well correlated with, and about threefold that, of Tc-99m DTPA. It was suggested that initial renal uptake of Tc 99m MAG3 may be an alternative to that of Tc-99m DTPA, with less dependence on background correction in evaluating differential renal function. PMID- 7874801 TI - Evaluation of the skull base by SPECT. A comparison with planar scintigraphy and computed tomography. AB - Computed tomography is currently the standard diagnostic tool for the evaluation of the skull base. The complex anatomy of this area is the primary reason why planar bone scintigraphy is often unsatisfactory; exact localization of abnormalities may be very difficult. These limitations may be overcome by SPECT. Seventeen patients with clinical features of basal skull involvement were assessed by CT, SPECT, and planar scintigraphy. Subsequent clinical diagnoses were malignancy in 15 patients, vasculitis in 1 patient, and osteomyelitis in 1 patient. Computed tomography with IV contrast was performed through the skull base at 5 mm intervals. Planar scintigraphy with Tc-99m MDP was followed by SPECT. Bony involvement compatible with the clinical findings was demonstrated by CT scans in 6 patients, by planar scintigraphy in 7 patients, and by SPECT in 9 patients. The abnormalities that were identified by CT were all identified by SPECT. This study suggests that, in imaging the skull base, SPECT is more sensitive and provides better anatomical localization than planar imaging and appears useful in patients with a negative CT study. PMID- 7874802 TI - Sarcoidosis of the axial skeleton. AB - Sarcoidosis of the bones in the hands and feet is not uncommon. However, sarcoidosis involving the axial skeleton is unusual. The authors present the case of a 37-year-old man with sarcoidosis who developed low-back pain. Radionuclide bone scan demonstrated abnormalities in the pelvis, spine, and scapulae. A bone scan directed open biopsy of an abnormality in diagnostic tissue from the ilium. PMID- 7874803 TI - Tc-99m MIBI uptake in pulmonary sarcoidosis. Preliminary clinical results and comparison with Ga-67. AB - During tumor imaging research, the authors incidentally discovered that Tc-99m MIBI is taken up by pulmonary sarcoidosis. In order to evaluate this uptake, they performed Tc-99m MIBI planar and SPECT imaging in 7 patients and compared it with Ga-67. Six out of 7 patients showed evident uptake of Tc-99m MIBI in enlarged hilar lymph nodes. One of the patients, who had been on corticosteroid treatment, showed only faint uptake (negative result), in whom Ga-67 uptake was seen in hilar lymph nodes although it was less evident than the uptake in the other patients. The lymph nodes were better demonstrated with Tc-99m MIBI. The fact that enlarged hilar lymph nodes in a patient on corticosteroid treatment showed faint uptake suggests that Tc-99m MIBI could be helpful for assessing the response to treatment. The preliminary experience in a limited number of patients showed that Tc-99m MIBI is taken up by pulmonary sarcoidosis and it appears to be a potential alternative to Ga-67. Further study is necessary to evaluate its ultimate role in pulmonary sarcoidosis imaging. PMID- 7874805 TI - Detection of esophageal carcinoma using Tc-99m MIBI SPECT imaging. AB - Thirty male patients, ranging in age from 41-78 years, with esophageal carcinomas underwent Tc-99m MIBI SPECT of the chest to evaluate the value of Tc-99m MIBI in the detection of esophageal carcinoma. In addition, Tc-99m MIBI SPECT of the chest was performed, for comparative purposes, in 10 normal patients who were referred because of suspected ischemic heart disease. Of the 30 patients with esophageal carcinoma, 22 epidermoid carcinomas (73%) were detected using Tc-99m MIBI chest SPECT, while eight carcinomas (27%) were not detected. In comparison, 10 of the control patients (100%) were not detected on the Tc-99m MIBI chest SPECT. In addition, the diagnostic sensitivity was not related to cell differentiation, the location, or the size of the carcinomas. These results suggest that the Tc-99m MIBI chest SPECT could be a helpful test to detect esophageal carcinoma. PMID- 7874804 TI - Detection of medullary carcinoma of the thyroid with I-131 MIBG. AB - Imaging with I-131 MIBG has proved useful for the detection of pheochromocytoma, neuroblastoma, and other neoplasms of neural crest origin. The authors present a case of a patient who was initially diagnosed as having follicular carcinoma of the thyroid in which I-131 MIBG played a key role in leading to the diagnosis of medullary carcinoma of the thyroid. Local and distant metastases were detected using I-131 MIBG imaging. Uptake of I-131 MIBG by medullary carcinoma of the thyroid has both diagnostic and therapeutic implications. PMID- 7874806 TI - In-111 labeled purified granulocytes in the diagnosis of synthetic vascular graft infections. AB - Indium-111 labeled enriched granulocytes should have improved accuracy in diagnosing synthetic vascular graft infections compared to labeled mixed leukocyte preparations because of the reduced numbers of reinjected erythrocytes and platelets, thereby reducing blood pool and nonspecific platelet adhesion to the graft. To test the use of enriched granulocytes in the diagnosis of vascular graft infections, the authors reviewed 153 studies in 106 patients. All were imaged with In-111 oxine labeled enriched autologous granulocytes prepared using Volex (American Critical Care, McGaw Park, IL) enhanced gravity sedimentation and Ficoll-Hypaque (Pharmacia Biotech, Piscataway, NJ; Winthrop Pharmaceuticals, New York, NY) double density centrifugation. The diagnosis of infection was established or refuted based on operative appearance of infection in one third of patients, and the clinical course over a mean 10-month follow-up period in the remainder. Of those patients with infection, 29 of 43 had positive imaging results that yielded a sensitivity of 67%. Of 100 patients without infection, 97 had negative imaging results that yielded a specificity of 97%. Compared to pooled data of studies using In-111 oxine labeled mixed leukocyte preparations, the sensitivity of enriched granulocytes appears lower and the specificity higher. The apparent reduced sensitivity may relate to the chronic nature of some graft infections and the markedly reduced number of reinjected lymphocytes in enriched granulocyte preparations compared to mixed leukocyte preparations. Although the specificity is very high using enriched granulocyte preparations, there may not be a significant advantage of the method over mixed leukocyte preparations. PMID- 7874807 TI - Tc-99m sulfur colloid demonstration of diffuse pulmonary interstitial extramedullary hematopoiesis in a patient with myelofibrosis. A case report and review of the literature. AB - A 60-year-old man with a myeloproliferative syndrome and extramedullary hematopoiesis had progressive respiratory and cardiac insufficiency during the previous 18 months, with advancing interstitial pulmonary disease on chest x-ray. During analysis of his respiratory disease, results of a transbronchial biopsy showed interstitial involvement with increased numbers of megakaryocytes and other panhematopoietic staining elements. Results of a bone marrow scan demonstrated diffuse replacement of pulmonary interstitium with bone marrow, as a component of known ongoing extramedullary hematopoiesis. PMID- 7874808 TI - Technegas versus krypton-81m gas as an inhalation agent. Comparison of pulmonary distribution at total lung capacity. AB - Exactly how the pulmonary distribution of inhaled radioactive gas and Technegas, or ultra-small aerosol particulates, differs from each other, is still uncertain. The authors compared the distribution of inhaled Kr-81 m gas and Technegas in the lungs at total lung capacity in 13 control subjects with no clinical conditions and 13 patients with various chest diseases. In normal lungs, there was no difference in the distribution ratios in the right and left lungs between inhaled Kr-81m gas and Technegas. However, there was a significant difference in the lungs of patients with pulmonary disease. Technegas tended to deposit more in the lung bases than did Kr-81m gas. Despite these statistical differences, they were visually, or qualitatively, similar. From a practical and clinical standpoint, Technegas seems to be useful as an inhalation agent, unless quantitative analyses are required. PMID- 7874809 TI - Scintigraphic appearances in patients with pulmonary infection and lung scintigrams of intermediate or low probability for pulmonary embolism. AB - Out of 294 patients with lung scintigrams of low or intermediate probability for pulmonary embolism, the appearances in 54 patients with a final diagnosis of pulmonary infection were reviewed. The most common finding was a matched defect in ventilation and perfusion occurring in 40 patients (76%). Regional reverse mismatch occurred in 13 patients (24%) and both appearances were found in one patient (2%). Reverse mismatch was also present in a further seven patients, four of whom had bronchial obstruction. Although occurring less frequently than matched defects, 81% of regional reverse mismatched defects were because of chest infection. The presence of regional reverse mismatch in patients investigated for pulmonary embolism suggests the alternative diagnosis of chest infection. PMID- 7874810 TI - Prediction of probability of pneumonectomy for lung cancer using Tc-99m MAA perfusion lung imaging. AB - Pulmonary perfusion scintigraphy with Tc-99m MAA was performed on 182 patients, on whom either pneumonectomy or lobectomy was performed, because of primary nonsmall-cell lung carcinoma. Among them, 76 underwent pneumonectomy, and 106 underwent lobectomy. The mean value of the perfusion fraction (PF) of the affected lung of the patients undergoing pneumonectomy was 32.3 +/- 13.6% (range, 4%-50%) and was less than that of the patients undergoing lobectomy, 43.5 +/- 4.5% (range, 27%-50%). The difference was statistically significant (t-test, t = 6.82; P < 0.001). Among the 28 patients whose PF of the affected lung was equal to or less than 30%, 26 underwent pneumonectomy and only 2 had a lobectomy. Among the 154 patients whose PF of the affected lung was more than 30%, 50 underwent pneumonectomy and 104 had a lobectomy. These result suggest that "30%" can be a cutoff value (Yates correction X(2) test, X2 = 33.09; P < 0.001). PMID- 7874811 TI - Clinical utility of bone SPECT scintigraphy in renal metastases from primary osteosarcoma. AB - Renal metastases from primary osteosarcomas are rather uncommon and rarely diagnosed early because the patients are asymptomatic and frequently die from other metastatic involvement before renal symptoms develop. The authors present a patient with two clinically silent renal metastases from primary osteosarcoma of the right femur 2 years after surgery of the primary lesion that was first detected on radionuclide bone imaging. Subsequently, a CT scan and a CT guided needle biopsy were performed for confirmation. The patient underwent a left nephrectomy and two separate lesions were proven to be metastatic osteosarcoma. The clinical importance of the nuclear bone scan in the initial management, as well as in the subsequent follow-up of patients after surgery, cannot be overemphasized. PMID- 7874812 TI - Incidental demonstration of Tc-99m MDP uptake in gallstones. PMID- 7874813 TI - Tampon artifact in bone scintigraphy. PMID- 7874814 TI - Technetium-99m MDP bone scan and MRI correlation in the detection of occult bone infarction. PMID- 7874815 TI - Sacral insufficiency fracture: half of an "H". PMID- 7874816 TI - Prominent gallium uptake associated with silicone implants in an asymptomatic patient. PMID- 7874817 TI - Cardiac amyloidosis detected by Tc-99m (V) DMSA myocardial uptake. PMID- 7874818 TI - Localization of Tc-99m pertechnetate in lymph node metastasis from occult thyroid carcinoma. PMID- 7874819 TI - Large thoracic aortic aneurysm seen on equilibrium blood pool imaging. PMID- 7874820 TI - Bowel visualization on bone scan because of protein losing enteropathy. PMID- 7874821 TI - Diagnostic significance of Tl-201-Ga-67 discordant pattern of biodistribution in AIDS. PMID- 7874822 TI - Reasons for condom utilization among high-risk adolescent girls. AB - Two hundred forty-eight adolescent girls responded to a list of 30 statements describing reasons for using and not using condoms. For 24 of the statements, most adolescents (> 70%) gave the same response regarding why they did or did not use condoms. Therefore, only the six remaining statements were used in further analyses. The relationship between the six statements and psychosexual history, condom use, and sexually transmitted disease (STD) history was examined. Those adolescent girls who had been sexually active longer were more likely to report lack of enjoyment as a reason that they did not use condoms (P < .03), and those adolescents who had been sexually active less time were more likely to report personal (P < .005) and partner (P < .0006) enjoyment of sex with condoms as a reason for using condoms. Longer relationships before intercourse were associated with having condoms available (P < .01) and partner insistence on their use (P < .02). Partner insistence on condom use was related to fewer episodes of sexually transmitted diseases (P = .03). These findings indicate the importance of relationship and partner variables in adolescent girls' perceptions of condom use. PMID- 7874823 TI - Sinusitis in status asthmaticus. AB - The relationship between sinusitis and status asthmaticus (SA) remains obscure. The purposes of this study were to determine the prevalence of abnormal sinus radiographs (SXRs) and investigate possible risk factors among unselected children admitted with SA. Eighty-eight patients over 2 years of age (range 2 to 16 years) consecutively admitted with SA were studied. The principal investigator, blinded to SXR findings, interviewed and examined the patients with respect to 10 physical parameters and 14 historical parameters. Two staff radiologists, blinded to the clinical findings, interpreted the SXRs. Relationship of historical and physical findings with positive SXRs was determined by statistical analysis. Twenty-seven percent of patients were found to have abnormal SXRs, manifesting two thirds or greater opacification of the sinuses. The mean age, sex, and race of patients with abnormal SXRs was not significantly different from those with normal films. A history of two or more admissions per year for SA, and, in children under 5 years of age, a history of chronic otitis media, and the physical finding of otitis media were significantly more frequent among patients with abnormal SXRs. Although not found to be statistically significant, a history of sinusitis and cough occurred more frequently in association with abnormal SXRs. PMID- 7874824 TI - Preventive care for patients with chronic illness. Multivitamin use in patients with cystic fibrosis. AB - Routine supplementation with multivitamins is recommended for all patients with cystic fibrosis (CF). The purpose of this study was to investigate how well patients at a large CF clinic follow recommendations for taking multivitamins and what factors affect use. A questionnaire was developed and sent to the 150 patients actively followed at our center. Of the 80 patients who returned the survey, only 47% followed clinic recommendations. Of those patients not taking extra supplements, serum vitamin A and E levels varied widely, although most were within the normal range (vitamin A 11-87 micrograms/dL, tocopherol 0.4-2.3 mg/dL, tocopherol/cholesterol 3.0-9.6 mg/g). Only 25% of respondents had known insurance coverage for vitamins. Gender or educational level did not affect adherence; however, those with minimal pulmonary disease (forced vital capacity [FVC] greater than 70% of predicted) were more likely to take vitamins than those with moderate or severe disease (P < .05). In addition to malabsorption, poor adherence should be considered by both CF specialists and primary-care providers as a cause of low serum vitamin A and E levels, especially in patients with moderate to severe lung disease. PMID- 7874825 TI - A perspective on controversies over neonatal circumcision. AB - Controversy continues to surround the issue of male circumcision, especially in the United States. The following report reviews the history of this practice, along with the medical and sociopolitical positions currently espoused. It is our conclusion that, as the safest and most commonly performed surgical procedure in this country, the benefits of posthetomy, which include a reduction in some kinds of cancer and sexually transmitted diseases, well outweigh the risks cited by those who oppose it. PMID- 7874826 TI - Initial management of hypernatremic dehydration in the breastfed infant. PMID- 7874827 TI - Nephrolithiasis in an infant with short-bowel syndrome. PMID- 7874828 TI - Organic dust toxic syndrome in a child. PMID- 7874829 TI - Survival following congenital clostridial sepsis in a premature newborn. PMID- 7874830 TI - Cardiac decompensation due to massive pericardial effusion. A manifestation of hypothyroidism in children with Down's syndrome. PMID- 7874831 TI - Kienbock's disease--avascular necrosis of the carpal lunate bone--in a 7-year-old girl with dermatomyositis. PMID- 7874832 TI - Smooth-muscle-cell proliferation and differentiation in neointima formation and vascular restenosis. PMID- 7874833 TI - Multiple transcripts of the neurofibromatosis type 1 gene in human brain and in brain tumours. AB - 1. Neurofibromatosis type 1 is a common hereditary disorder characterized by the presence of multiple neurofibromas and cafe-au-lait spots, and is frequently associated with intellectual handicaps and brain tumours. The gene responsible for neurofibromatosis (the NF1 gene) codes for a protein of 2818 amino acids, termed neurofibromin, which has a domain related to mammalian ras GTPase activating protein. 2. The NF1 gene gives rise to multiple transcripts generated by alternative splicing, that encode neurofibromin and its isoforms. These include type I mRNA coding for neurofibromin, type II mRNA coding for neurofibromin containing the insertion of 21 amino acids in the GTPase-activating protein-related related domain and mRNA coding for an N-terminal isoform lacking the GTPase-activating protein-related domain (N-isoform). 3. In the present study, the relative levels of mRNAs encoding type I, type II and N-isoform were determined by S1-nuclease mapping analysis in human brain tissue and in primary brain tumours obtained from patients with tumours unrelated to neurofibromatosis type 1. 4. These three mRNAs were expressed in all ten brain tumours and in every region of the brain examined, with the highest levels found in the cerebellum. Type I mRNA was the predominant form in the human brain except for the pons, whereas type II mRNA was predominantly expressed in eight out of ten primary brain tumours. 5. In contrast, N-isoform mRNA was similarly expressed in normal brain tissue and brain tumours. 6. These findings suggest that neurofibromin and its isoforms have important physiological roles in the human brain and that the altered expression of type I and type II mRNAs in brain tumours may be related to the tumorigenesis. PMID- 7874834 TI - Primary localized orbital amyloidosis composed of the immunoglobulin gamma heavy chain CH3 domain. AB - 1. Primary orbital amyloidosis is a rare form of localized amyloidosis in which the precursor protein has not previously been identified. We report here the first extraction of amyloid fibrils from a tissue biopsy containing orbital amyloid, and characterization of the fibril protein. 2. The N-terminal nine residues were identical with residues 278-286 and 275-283 of the third constant (CH3) domains of IgG1 and IgG4 gamma heavy chains, respectively. The mass of the fibril subunit protein was 6125Da by time-of-flight mass spectrometry, compared with the expected masses of 6169.9Da and 6214.9Da for the CH3 domains of gamma 1 from residue 278 and gamma 4 from residue 275, respectively. The fibril protein thus appeared to consist exclusively of an immunoglobulin heavy chain constant domain. 3. Only two examples of immunoglobulin heavy chain derived amyloid have been reported previously and both of these, as well as all published cases of the usual immunoglobulin light chain derived amyloid, contained variable domain sequence. The present case therefore represents a form of local, presumably clonal, B-cell/plasma-cell disorder characterized uniquely by deposition of an amyloidogenic immunoglobulin heavy chain constant domain fragment. PMID- 7874835 TI - Absence of mutations in the Gs alpha and Gi2 alpha genes in sporadic parathyroid adenomas and insulinomas. AB - 1. Activating mutations of the alpha-subunits of the Gs and Gi2 proteins give rise to the oncogenes gsp and gip2, respectively, which are found in a variety of endocrine tumours. 2. In this study the polymerase chain reaction and direct sequencing have been used to screen a small sample of parathyroid adenomas and insulinomas for these mutations. 3. No mutations were identified in nine insulinomas and 13 parathyroid adenomas screened for gsp, and 11 parathyroid adenomas and four insulinomas screened for gip2. In addition, two gastrinomas from patients with multiple endocrine neoplasia type 1 were found to be negative for both oncogenes. 4. This is the first report of screening for gip2 in parathyroid adenomas and gsp/gip2 in insulinomas, and it extends the range of tumours examined for these oncogenes. PMID- 7874836 TI - Ammonium chloride inhibits pyruvate oxidation in rat liver mitochondria: a possible cause of fatty liver in Reye's syndrome and urea cycle defects. AB - 1. Earlier studies with liver slices showed that inhibition by NH4+ of the oxidation of palmitate to CO2 was greater than total oxidation, whereas salicylate exerted a stronger inhibitory effect on the latter. We have now investigated the effects of NH4Cl and salicylate on ADP-induced O2 consumption by mitochondria (State 3 rate) respiring on pyruvate, and oxidation of [1-14C]- and [2-14C]-pyruvate to 14CO2. 2. The rate of State 3 respiration was inhibited and plateaued at 45% with 10 mmol/l NH4Cl. 3. Oxidation of [1-14C]pyruvate was not significantly affected by either NH4Cl or salicylate. Oxidation of [2 14C]pyruvate was strongly inhibited and plateaued at 70% with 1 mmol/l NH4Cl (IC50 = 0.125 mmol/l). ADP (1 mmol/l) increased the rate of decarboxylation of [2 14C]pyruvate but the extent of NH4Cl inhibition was not affected. Salicylate had a slight activating effect in the absence or presence of NH4Cl. 4. These results indicate that NH4Cl inhibits the oxidative metabolism of acetyl-CoA in the tricarboxylic acid cycle. Therefore, inhibition of fatty acid oxidation to acetyl CoA as well as its further oxidative metabolism occurring under hyperammonaemia (> 0.1 mmol-1.49 mmol/l in Reye's syndrome patients) may be one of the causes of fatty acidaemia. 5. The cumulative inhibitory effects of NH4+ and fatty acyl derivatives on mitochondrial oxidative metabolism and production of ATP, as well as the uncoupling effects of salicylate, may contribute to some of the pathophysiology observed in patients with Reye's syndrome, and enzyme defects of the urea cycle. PMID- 7874837 TI - Serum vitamin A and E concentrations in acute falciparum malaria: modulators or markers of severity? AB - 1. To assess the association between vitamin A, vitamin E and the clinical course of severe malaria, serial morning blood samples were taken from 24 Vietnamese patients, aged 18-62 years, receiving intensive treatment for complicated Plasmodium falciparum infections. A single fasting blood sample was also taken from 10 control subjects aged 22-45 years. Serum retinol, carotene and vitamin E concentrations were measured by h.p.l.c. 2. Admission serum retinol concentration was depressed relative to that of the control subjects (0.69 +/- 0.35 versus 1.86 +/- 0.41 mumol/l mean +/- SD, P < 0.001) and correlated inversely with indices of hepatic function, but positively with the simultaneous serum creatinine concentration (P < 0.05). During the first week of treatment, serum retinol concentration increased in parallel with improving liver function, whereas serum creatinine concentration remained elevated in the majority of patients. Serum alpha- and beta-carotene concentrations remained depressed throughout. 3. Serum vitamin E concentration, corrected for total serum cholesterol concentration in the form of a ratio, was also depressed at presentation (3.1 +/- 1.8 x 10(3) versus 4.2 +/- 0.8 x 10(3) in control subjects; P < 0.05), but tended to be higher than the control value at the time of discharge (0.1 > P > 0.05); there was a significant correlation between admission ratio and parasite clearance time (P = 0.04). 4. On the basis of this and previous studies, vitamin A replacement could be considered in selected severely ill patients without renal impairment. As found previously in animal models, depressed vitamin E levels may have a beneficial effect on the course of malarial infection. PMID- 7874838 TI - Renal impairment associated with the pre-operative administration of recombinant interleukin-2. AB - 1. The T-cell-derived cytokine interleukin-2 may be used to reverse the immune suppression associated with major surgery. However, both major surgical procedures and recombinant interleukin-2 therapy are known to induce renal dysfunction. 2. Eighteen patients were randomized to receive either recombinant interleukin-2 (18 x 10(6) i.u./day) or placebo, given subcutaneously for 3 days before undergoing curative colorectal cancer surgery. Indices of renal function were determined pre-operatively and for 21 days after surgery. 3. Pre-operative recombinant interleukin-2 was found to significantly increase, compared with placebo controls, N-acetyl-beta-D-glucosaminidase [peak levels 28 (SEM 2) versus 11 (SEM 3) i.u./mmol of Cr] and gamma-glutamyltransferase [peak levels 5.3 (SEM 0.6) versus 2.4 (SEM 0.2) i.u./mmol/l] and decrease urinary fractional excretion of sodium [peak difference 0.32 (SEM 0.06) versus 0.76 (SEM 0.08)] (all P < 0.05). Significantly increased urinary excretions of creatinine, N-acetyl-beta-D glucosaminidase and gamma-glutamyltransferase were also identified after surgery. All variables returned to pretreatment limits by the seventh day post operatively, except N-acetyl-beta-D-glucosaminidase, which was still significantly elevated 21 days after surgery. No differences in the serum concentrations of sodium, creatinine or urea were observed before or after surgery in either group. 4. Recombinant interleukin-2, when given in the preoperative period, was associated with significant renal dysfunction. However, routine monitoring of serum indices (i.e. sodium, urea, creatinine and albumin) failed to detect such renal damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874839 TI - Glomerular filtration rate and segmental tubular function in the early phase after transplantation/uninephrectomy in recipients and their living-related kidney donors. AB - 1. Glomerular filtration rate and sequential tubular function were investigated in 18 adult renal transplant recipients and in their matched, adult living related kidney donors before and 5 days after transplantation/uninephrectomy. At day 54, 13 donors and 11 recipients were re-investigated. Sixteen of these constituted eight matched pairs. This reduction in the study population was caused by the application of two withdrawal criteria. 2. In the recipients glomerular filtration rate was unchanged at day 5 and had increased to 61 ml/min at day 54 (P < 0.05). In the donors glomerular filtration rate had increased to 59 ml/min by day 5 (P < 0.01) and was unchanged at day 54. 3. In the recipients lithium clearance was unchanged at day 5 and had increased to 23 ml/min at day 54 (P < 0.01). In the donors the lithium clearance had increased by day 5 (P < 0.01). 4. In the recipients the absolute proximal fluid reabsorption rate was about 36 ml/min throughout the study period. In the donors the absolute proximal fluid reabsorption rate had increased to 42 ml/min by day 5 (P < 0.05) and increased further to 44 ml/min by day 54 (P < 0.01). 5. In the recipients sodium clearance increased from 0.54 ml/min to 2.10 ml/min at day 54 (P < 0.01). In the donors it increased from 0.64 ml/min to 0.99 ml/min at day 54 (P < 0.05). 6. Donor-recipient comparison showed that at day 54 there was no significant difference with regard to glomerular filtration rate, lithium clearance, absolute and fractional proximal fluid reabsorption rate and absolute distal sodium reabsorption rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874840 TI - Dietary salt extremes and renal function in rats: effect of atrial natriuretic factor. AB - 1. Chronic reduction of salt intake can reduce the natriuretic effect of exogenously administered atrial natriuretic factor. The purpose of this study was to elucidate the intrarenal site(s) of such atrial natriuretic factor resistance. Renal clearance and collecting duct microcatheterization experiments were made before and during infusion of atrial natriuretic factor in three groups of rats: group 1 consisted of rats fed a high salt diet (8% NaCl) for 1 week before the experiment; group II were fed a low salt diet (< 0.008%); group III received the same low salt diet, but were acutely replenished with salt at the time of experiment. 2. Baseline sodium chloride excretion was 6480 +/- 810 nmol min-1 g-1 kidney weight in group 1 compared to 99 +/- 16 in group 1. Fractional reabsorptions in the medullary collecting duct were 37 +/- 6% and 95 +/- 2% of delivered load, respectively (P < 0.05). The fractions of filtered sodium remaining at the beginning of the medullary duct were 6.6 +/- 1.0% of filtered load in group 1 and 2.7 +/- 0.7% in group II (P < 0.05), indicating increased tubular reabsorption in group II, not only in the medullary duct, but also in upstream nephron segments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874841 TI - Effects of intravenous calcitriol on lipid profiles and glucose tolerance in uraemic patients with secondary hyperparathyroidism. AB - 1. Secondary hyperparathyroidism in chronic renal failure may contribute to abnormalities of lipid metabolism and glucose tolerance. Amelioration of secondary hyperparathyroidism has been reported to mitigate the hyperlipidaemia and improve glucose tolerance experimentally. 2. The effect of the partial suppression of hyperparathyroidism by intravenous calcitriol on lipid levels and glucose tolerance was studied in 15 haemodialysis patients with secondary hyperparathyroidism. All received intravenous calcitriol 1 microgram at the end of haemodialysis thrice weekly for eight weeks. Oral glucose tolerance test and plasma lipid profiles including triglyceride, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apoprotein A-I and apoprotein B were determined simultaneously before and after eight weeks of therapy. 3. Before calcitriol treatment, uraemic patients with secondary hyperparathyroidism displayed a significant higher triglyceride and a significant lower HDL-C and apoprotein A-I as well as marked glucose intolerance with an increment of the area below the glucose curve when compared with healthy control subjects. 4. After eight weeks of calcitriol treatment, there was a significant decrement in serum intact parathyroid hormone (476.45 +/- 48.33 versus 191.37 +/- 30.17 ng/l, P < 0.001) and plasma triglyceride (2.24 +/- 0.34 versus 1.80 +/- 0.29 mmol/l, P < 0.05) as well as a significant increment of plasma apoprotein A-I (38.13 +/- 2.14 versus 44.19 +/- 2.18 mumol/l, P < 0.05), whereas there was no significant change in serum total cholesterol, LDL-C, HDL-C, and apoprotein B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874842 TI - Cardiac muscle protein gene expression in the endotoxin-treated rat. AB - 1. Sepsis is associated with marked changes in cardiac muscle protein synthesis. Such changes may be the result of altered transcription of specific myofibrillar protein mRNAs. 2. In order to investigate myofibrillar protein gene expression, a rat model of sepsis was used. Adult rats were given a single sub-lethal dose of lipopolysaccharide by the intraperitoneal route. At various times thereafter, rats were killed and ventricular muscle was removed. RNA was extracted and transferred to nylon membranes. Changes in expression of mRNA for alpha- and beta myosin heavy chain, alpha-actin, cardiac troponin C and carbonic anhydrase III were detected by Northern hybridization. 3. After treatment with lipopolysaccharide, mRNA for beta-myosin heavy chain increased to 260% of control values at 24 h and reached a maximum of 310% at 48 h. alpha-Myosin heavy chain mRNA levels fell to 72% of control values at 24 h. mRNA levels for alpha-actin, cardiac troponin C and carbonic anhydrase III remained unchanged. 4. In order to investigate the role of tumour necrosis factor-alpha in this process, some rats were pretreated with monoclonal antibody against tumour necrosis factor-alpha before receiving lipopolysaccharide. Such animals showed an absence of tumour necrosis factor-alpha bioactivity in plasma, but changes in myocardial protein mRNA levels were no different from those seen in animals receiving lipopolysaccharide alone. 5. The reduction in protein synthesis in cardiac muscle in sepsis does not appear to be the result of reduced expression of genes for structural or soluble muscle protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874843 TI - Lack of importance in humans of the slow component of the response of force to an increase in cardiac muscle length. AB - 1. An increase in length in isolated animal muscles causes an immediate increase in contractile force, which is followed by a slower further progressive increase: the slow component. However, the pressure-volume concept, used in characterizing left ventricular function, is dependent on a constant relationship between pressure and volume. 2. We therefore examined the possible occurrence of the slow inotropic component of the response to cardiac muscle stretch in man at cardiac catheterization. 3. Human subjects undergoing left heart catheterization for clinical indications were studied. The development of the slow component was studied by measurement of rate of rise in left ventricular developed pressure and the time course after an increase in end-diastolic volume. 4. No evidence for any slow component was elicited. 5. It is concluded that the slow component of force (or pressure) increase after an increase in cardiac muscle length (or volume) does not have a role in the human heart in situ. PMID- 7874844 TI - Effects of leg muscle pumping and tensing on orthostatic arterial pressure: a study in normal subjects and patients with autonomic failure. AB - 1. The effects of leg muscle pumping (tiptoeing) and tensing (leg-crossing) on orthostatic blood pressure were investigated in six healthy adult subjects (aged 28-34 years) and in seven patients with severe hypoadrenergic orthostatic hypotension (aged 20-65 years). 2. Finger arterial pressure was monitored. Relative changes in left ventricular stroke volume were computed by a pulse contour method. 3. Tiptoeing increased mean arterial pressure (7 +/- 5 mmHg) in the healthy subjects, but not in the patients, whereas cardiac output increased in both groups, although by more in the healthy adults than in the patients (35 +/- 10% versus 20 +/- 11%, P < 0.05). Systemic vascular resistance decreased substantially in both groups while tiptoeing. Leg-crossing did not affect arterial pressure in the healthy subjects, although stroke volume had increased. In contrast, in the patients an increase in cardiac output (16 +/- 12%) and mean blood pressure (13 +/- 13 mmHg) was observed. 4. Tiptoeing and leg-crossing have different effects on orthostatic blood pressure in healthy adult subjects and in patients with autonomic failure. In normal humans, tiptoeing increases arterial pressure, whereas leg-crossing has little effect. In the patients, in contrast, tiptoeing has little effect, whereas leg-crossing increases arterial pressure considerably. Patients with autonomic failure should be instructed to apply leg crossing to combat orthostatic dizziness. PMID- 7874845 TI - Total forearm blood flow as an indicator of skeletal muscle blood flow: effect of subcutaneous adipose tissue blood flow. AB - 1. In studying forearm skeletal muscle substrate exchange, an often applied method for estimating skeletal muscle blood flow is strain gauge plethysmography. A disadvantage of this method is that it only measures total blood flow through a segment of forearm and not the flow through the individual parts such as skin, adipose tissue and muscle. 2. In the present study the contribution of forearm subcutaneous adipose tissue blood flow to total forearm blood flow was evaluated in lean (% body fat 17.0 +/- 2.2) and obese males (% body fat 30.9 +/- 1.6) during rest and during infusion of the non-selective beta-agonist isoprenaline. Measurements were obtained of body composition (hydrostatic weighing), forearm composition (magnetic resonance imaging) and of total forearm (venous occlusion plethysmography), skin (skin blood flow, laser Doppler), and subcutaneous adipose tissue blood flow (133Xe washout technique). 3. The absolute forearm area and the relative amount of fat (% of forearm area) were significantly higher in obese as compared to lean subjects, whereas the relative amounts of muscle and skin were similar. 4. During rest, the percentage contribution of adipose tissue blood flow to total forearm blood flow was significantly higher in lean compared with obese subjects (19 vs 12%, P < 0.05), whereas there were no differences in percentage contribution between both groups during isoprenaline infusion (10 vs 13%). Furthermore, the contribution of adipose tissue blood flow to total forearm blood flow was significantly lower during isoprenaline infusion than during rest in lean subjects (P < 0.05), whereas in the obese this value was similar during rest and during isoprenaline infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874846 TI - Plasma kinins increase after angiotensin-converting enzyme inhibition in human subjects. AB - 1. In patients treated with angiotensin-converting enzyme inhibitors, kinin related effects have been postulated repeatedly, but information on changes in plasma kinin levels in these patients is sparse. Difficulties in the measurement of plasma kinins account for this, at least in part. 2. The main purpose of the present study was to investigate, in normal human subjects, the effect of the angiotensin-converting enzyme inhibitor quinapril on plasma kinins. 3. High affinity antisera (Kd < 10(-11) mol/l) of C-terminal specificity were raised in rabbits for radioimmunoassay of immunoreactive kinins activating the bradykinin B2-receptor, and three different liquid- and solid-phase extraction methods for plasma kinins were evaluated. Ethanol and subsequent petroleum ether extraction of 5-40 fmol of bradykinin added to plasma yielded recoveries of 39 +/- 16% (mean +/- SD); normal kinin levels in human plasma were 18.6 +/- 3.3 pmol/l (mean +/- SEM). Solid-phase extraction on urea-equilibrated phenylsilylsilica produced recoveries of 89 +/- 5% and normal values of 36.4 +/- 18 pmol/l. Finally, with an assay based on ethanol extraction alone, recoveries of 100 +/- 16% and normal values of 16.8 +/- 5.8 pmol/l were obtained, with a detection limit of 1.5 fmol/ml of plasma. Blanks were below the detection limit. Serial dilution of plasma extracts (n = 4) provided linear kinin concentrations (r = 0.99). For two different plasma pools, coefficients of variation for within-assay precision were 16.7% and 21.7%, respectively. Between-assay coefficients of variation were 12.8% and 17.4%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874847 TI - Regional fat distribution by dual-energy X-ray absorptiometry: comparison with anthropometry and application in a clinical trial of growth hormone and exercise. AB - 1. The purpose of this study was to determine the suitability of ratios derived from dual-energy X-ray absorptiometry (DXA) whole body scans to assess regional fat distribution in older men and women by comparing them with the waist-to-hip ratio (WHR) and to evaluate their clinical utility by applying them in a clinical trial involving resistance exercise and recombinant human growth hormone. 2. Sixty-four healthy older adults (39 women and 25 men), aged 65-82 years, served as subjects. The ratios of trunk fat-to-total fat, trunk fat-to-body weight, trunk fat-to-limb fat and trunk fat % were determined by DXA. WHR was assessed on the same day, as was the ratio of subscapular/triceps skinfolds in men. Cardiovascular disease risk factors, functional capacity and serum lipids were also assessed. 3. A moderate relationship (r = 0.36-0.54) between the WHR- and DXA-derived ratios were observed for both men and women. Both DXA and WHR showed similar associations with cardiovascular disease risk factors. However, in men, all DXA ratios were able to detect subtle changes in regional fat distribution resulting from daily administration of recombinant human growth hormone in conjunction with resistance exercise for 10 weeks, whereas the WHR or subscapular/triceps ratios did not. 4. This suggests that DXA-derived ratios may be more sensitive than conventional anthropometric methods in the assessment and categorization of body fat distribution. PMID- 7874848 TI - A comparison of bone mineral density between Caucasian, Asian and Afro-Caribbean women. AB - 1. We analysed the lumbar spine (L2-L4) and femoral neck bone mineral density results of Caucasian (n = 2232), Asian (Indian sub-continent) (n = 153) and Afro Caribbean (n = 102) women referred for bone densitometry over a 30 month period. To assess the risk of osteoporosis, the results of Caucasian and Asian women were compared with those of a reference Caucasian population supplied by Lunar. 2. Subject characteristics were similar in all three groups, other than expected ethnic differences in stature and weight. We found that lumbar spine and femoral neck bone mineral density in Caucasians was lower than in Afro-Caribbeans, but higher than in Asians. Consistent with this, bone mineral density was also lower in Asians as compared with the reference Caucasian population, both at the lumbar spine and femoral neck. As a consequence, a higher proportion of Asian women were classified as being at increased risk of osteoporosis than Caucasian women. 3. Since ethnic differences in skeletal size might influence bone mineral density, we also obtained values for bone mineral content in Caucasian and Asian women that were corrected for projected skeletal area, and weight and years since menopause, using regression equations derived from the Caucasian study population. After this analysis, the difference in bone mineral content between Caucasians and Asians at the lumbar spine disappeared, while that at the femoral neck persisted. 4. We conclude that the assessment of risk of osteoporosis in Asian women by comparing bone mineral density with a reference Caucasian population may have limited validity because of the influence of skeletal size on such measurements. PMID- 7874849 TI - Bone density and mineral metabolism in thyroidectomized patients treated with long-term L-thyroxine. AB - 1. A decreased bone mass has been reported in patients with endogenous hyperthyroidism, but the effect on bone density and mineral metabolism of thyroxine administration in thyroidectomized patients is still controversial. To further contribute to this debate, we studied 25 women thyroidectomized for thyroid cancer on long-term treatment with thyroid-stimulating hormone suppressive doses of L-thyroxine. Twenty-one sex- and age-matched normal subjects were also studied as a control group. 2. The bone density of the spine and serum calcitonin, calcitriol and parathyroid hormone concentrations were not different when the whole patient group was compared with the control subjects, nor when the patients and control subjects were compared according to their menopausal status. However, post-menopausal thyroidectomized patients showed significantly lower bone mass (P < 0.001) than premenopausal patients. 3. L-Thyroxine-treated patients showed significantly higher levels of bone alkaline phosphatase and urine hydroxyproline excretion than control subjects (P < 0.003 and P < 0.001, respectively). These differences were still present when patients and control subjects were analysed according to their menopausal status. However, bone alkaline phosphatase was significantly higher in postmenopausal than in premenopausal women only in L-thyroxine-treated patients (P < 0.05). In postmenopausal L-thyroxine-treated patients a negative correlation between time since menopause and bone mass (P < 0.05) and a positive correlation between bone alkaline phosphatase and hydroxyproline excretion (P < 0.03) were also found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874850 TI - Dietary energy, glucocorticoids and the regulation of long bone and muscle growth in the rat. AB - 1. The influence of dietary energy restriction and corticosterone on long bone and muscle growth, and their interrelationships, was studied in rats fed a range of restricted amounts of diets containing increasing concentrations of protein, thus maintaining constant protein intakes. Tibial length and epiphyseal cartilage width were measured radiographically. 2. In experiment 1, tibial length and gastrocnemius muscle growth were examined in ad libitum fed rats and during 4 days of severe energy restriction (25% ad libitum intake), starvation and ad libitum feeding with corticosterone treatment (10 mg/100 g), a mediator of the response to energy restriction. Weight loss occurred in all groups. Tibial growth continued in the 25% and starvation groups albeit at reduced rates with the inhibition of starvation > 25% group (P < 0.05), but was arrested after 2 days of corticosterone treatment. 3. Muscle growth inhibition was proportional to tibial growth inhibition of the 25% group, insofar as the muscle/bone ratio (W/L), was maintained. This inter-relationship between muscle and bone growth previously reported for ad libitum high-protein-fed rats, is likely to reflect the anabolic influence of bone on muscle via passive muscle stretching induced by length growth. For both starvation and corticosterone groups the muscle/bone ratio fell (P < 0.05 compared with the ad libitum group), suggesting that muscle growth inhibition included an additional direct catabolic influence of starvation and corticosterone treatment. 4. In experiment 2, measurements of bone, muscle and liver growth were made in rats fed 75%, or 50% and 25% ad libitum intakes with corticosterone treatment for 8 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874851 TI - Influence of dietary protein, energy and corticosteroids on protein turnover, proteoglycan sulphation and growth of long bone and skeletal muscle in the rat. AB - 1. We report here the extent to which changes in protein turnover contribute to the previously described inhibition of growth of rat tibial length and skeletal muscle mass in response to protein deficiency [1], energy restriction and corticosterone treatment [2]. Measurements of 35S uptake in vivo also enabled the qualitative pattern of changes in proteoglycan synthesis in bone and muscle to be established. 2. Protein deficiency was examined by ad libitum feeding of 20%, 7%, 3.5% and 0.5% protein diets with measurements at 1, 3 and 7 days (all diets), and 14 and 21 days (0.5% protein). In bone this induced delayed inhibition of tibial growth with parallel inhibition of protein synthesis, as measured by the phenylalanine flooding dose method. This was mediated by reductions in both ribosomal capacity (RNA/protein ratio) and activity (protein synthesis/RNA) in the 0.5% protein group. The pattern of inhibition of proteoglycan sulphation, measured as 35S uptake 60 min after injection of a tracer dose of labelled sulphate, was similar to that of protein synthesis. 3. In muscle there was an intermediate graded inhibition of protein synthesis by protein deficiency, mediated by reductions in both ribosomal capacity and activity in the 0.5% protein group, which preceded growth inhibition in the 7% and 3.5% groups, and which was progressive with time. Transient increases in proteolysis contributed to the growth inhibition is some groups, but the rate fell eventually in the 0.5% group. The pattern of response of proteoglycan sulphation differed from protein synthesis with a delayed inhibition, but with subsequent marked reduction. 4. Energy restriction was induced by diets fed for 4 or 8 days at 75%, 50% and 25% ad libitum intakes with protein intakes held constant, and corticosterone treatment involved a dose of 10 mg day-1 100-1 g (subcutaneous) with ad libitum feeding. In bone this induced a pattern of length growth inhibition which was dissociated from inhibition of protein synthesis in the moderately restricted (75% and 50%) groups. Only in the 25% group and in the 8 day corticosterone group was protein synthesis inhibited, through reductions in ribosomal capacity and activity. 35S uptake was also dissociated from growth inhibition, with reduced 35S uptake observed only after corticosterone treatment or 8 days of the 50% or 25% diets. 5. In muscle the energy restriction and corticosterone treatment induced parallel inhibitions of growth and protein synthesis, mediated by similar graded reductions in the RNA/protein ratios and in the 25% group in the KRNA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7874852 TI - Prolonged changes in protein and amino acid metabolism after zymosan treatment in rats. AB - 1. Intraperitoneal injections of zymosan were given to rats, according to a modified procedure, in order to create a pattern of illness with an acute critical phase for 36 h followed by a prolonged recovery phase lasting for at least 10 days. Changes in amino acid and protein metabolism were studied in both phases. 2. Differences between this modified and the original zymosan model are a lower mortality (16%), which is limited to the first 36 critical hours, and the absence of signs of severe illness during the prolonged recovery phase. 3. Wasting of muscle protein and decreased protein synthesis rates in muscle were observed during the acute phase of illness. Liver size and liver protein synthesis rates were increased during the same period. The decrease in the total amount of muscle protein and the increase in liver weight were still present 12 days after zymosan treatment, despite a normalization of protein synthesis rates. Large decreases were observed in the concentrations of the conditionally essential amino acids glutamine and arginine in muscle over 6 days. Decreases in plasma glutamine and arginine on day 12 after zymosan indicated that the rats were still not fully recovered on this day. 4. We conclude that injection of a single dose of zymosan in rats leads to metabolic derangements both during the acute phase of critical illness and during the prolonged recovery phase. The model seems suited for investigating the biochemical mechanisms behind these metabolic derangements and for studying therapeutic and nutritional interventions during recovery from critical illness. PMID- 7874853 TI - Assessment of the salt-arterial pressure relationship in mild hypertensive subjects by 24-hour ambulatory monitoring. AB - 1. We have assessed the relationship between salt intake and 24 h ambulatory arterial pressure in middle aged men with essential hypertension. 2. During the run-in phase (1 month) we estimated the habitual sodium intake (the average Na excretion of two 24 h urine collections) of each participant (n = 14). In the randomized and crossover part of the study we contemplated a 'habitual' sodium intake phase, in which each individual received a fixed diet (about 30 mmol of Na+ and 65 mmol of K+) with additional salt so as to equalize the average intake of the run-in phase, as well as high sodium phases (habitual intake +50 and +100 mmol/day) and low sodium phases (habitual intake -50 and -100 mmol/day). After the trial, 10 patients underwent an additional week of fixed salt intake to assess the reproducibility of 24 h ambulatory monitoring. 3. Average 24 h arterial pressure at habitual sodium intake was significantly lower than that at high intake and significantly higher than at low sodium intake. Clinic arterial pressure showed similar trends but only systolic pressure changes at low sodium intake achieved statistical significance. 4. Analysis of the data on an individual basis showed a linear increase in 24 h mean arterial pressure with increasing levels of sodium intake in all but two cases (flat response in one case and a non-linear rise in the other case). The response pattern of clinic measurements was much less homogeneous. In the aggregate, there was a highly significant linear trend for ambulatory arterial pressure to rise with increasing levels of salt intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874854 TI - Impaired left ventricular relaxation and arterial stiffness in patients with essential hypertension. AB - 1. This study was designed to determine how left ventricular relaxation function in patients with essential hypertension is impaired by arterial haemodynamic load that is increased in early ejection phase. These patients did not suffer from cardiac hypertrophy or disturbed coronary perfusion. We used a high-fidelity multisensor catheter to record pressure and flow signals in the ascending aorta. The timing and magnitude of wave reflection were obtained by decomposing the measured waves into their forward and backward components. Radionuclide angiography was employed to obtain the time-activity curve. The left ventricular relaxation function was assessed by analysing the time-activity curve, which was filtered using Fourier expansion with the number of harmonics for minimum error. 2. In comparison with age-matched normotensive subjects (seven subjects with mean blood pressure 97 mmHg), hypertensive subjects (seven subjects with mean blood pressure 138 mmHg) had a shorter backward wave arrival time (193 +/- 26 versus 258 +/- 35 ms) and a higher reflection factor (0.58 +/- 0.12 versus 0.42 +/- 0.07). Isovolumic relaxation period was prolonged in hypertensive subjects (118 +/- 19 versus 90 +/- 19 ms). There was an inverse correlation between isovolumic relaxation period and backward wave arrival time in all 14 subjects (r = -0.67, P < 0.05). In contrast, there were no significant differences in cardiac output and time to peak ejection rate between the two groups. 3. Our analyses revealed that early return of the enhanced wave reflection may profoundly impair left ventricular relaxation function in patients with hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874855 TI - Low-frequency spontaneous fluctuations of R-R interval and blood pressure in conscious humans: a baroreceptor or central phenomenon? AB - 1. We have tested the hypothesis that the non-respiratory, low-frequency (around 0.1 Hz) fluctuations of heart rate variability are generated by the baroreflexes, but with a delay caused by the slower response of the efferent sympathetic arm, (compared with the vagus), in 11 healthy subjects (mean age +/- SD 27 +/- 5 years). 2. In random order, at the onset of 20 s of apnoea starting at end expiration, we applied either 600 ms neck suction (-40 mmHg) to the carotid sinus region, or no stimulus (anticipation control), or a loud whistle (alerting control), every 60 s, for 30 min. (i.e. 10 of each 'stimulus'). We recorded neck pressure, blood pressure (Finapres), R-R interval (ECG), infra-red plethysmographic skin blood flow and respiration (impedance). By subtracting the alerting response from the neck suction response we obtained the responses caused purely by baroreceptor stimulation. 3. The initial reflex bradycardia and hypotension was followed by arteriolar vasoconstriction, presumably due to recompensation by the baroreflex, and then by a further reflex bradycardia producing a decaying oscillation of the R-R interval about the control R-R. The period of this damped oscillation was 0.103 +/- 0.024 Hz, similar to the frequency of the low-frequency peak obtained by power spectral analysis of heart rate variability (0.093 +/- 0.016 Hz, not significant) at rest. These two values were significantly correlated in individual subjects (r = 0.715, P < 0.025). 4. These findings support the hypothesis that the low-frequency waves of heart rate variability can be generated from baroreceptor sensed blood pressure fluctuations. PMID- 7874856 TI - Sympathetic overactivity in subjects complaining of unexplained fatigue. AB - 1. Theoretical and practical considerations suggest that in subjects complaining of fatigue, in the absence of evident organ dysfunction, an alteration in the autonomic nervous system might be present as a functional correlate. 2. Autoregressive spectral analysis of R-R interval variability from a surface ECG, was used in healthy control subjects (n = 24, age 45 +/- 4 years) and in subjects complaining of unexplained fatigue (n = 53, age 46 +/- 9 years) to obtain quantitative indices of the state of the sympathovagal balance, both at rest and during a mental stimulus (mental arithmetic), capable of enhancing sympathetic drive. Sympathetic and vagal modulations were inferred from the normalized powers of the low frequency and high frequency spectral components respectively. 3. We observed in patients, at rest, a prevailing low frequency component of R-R variability (patients low frequency = 73 +/- 11, control subjects 51 +/- 10 normalized units, P < 0.05). The responsiveness to mental arithmetic was reduced in patients as compared with controls. Systolic blood pressure variability did not differ. This suggested a selective imbalance in autonomic control of the sinoatrial node, characterized by sympathetic predominance as well as by vagal withdrawal, at rest. 4. The possibility of discriminating patients from control subjects on the basis of simple non-invasive functional markers might provide a better understanding of the mechanisms, clinical evolution and outcome of conditions such as the chronic fatigue syndrome, which lack ordinary evidence of disease, but comprise, as physiopathological correlate, a quantitative alteration of autonomic control. PMID- 7874857 TI - Reflex sympathetic dystrophy: result of autonomic denervation? AB - 1. To investigate the nature of sympathetic dysfunction in the pathogenesis of reflex sympathetic dystrophy, the microcirculatory vasoconstrictive responses to dependency were investigated in the skin of the hand of 76 reflex sympathetic dystrophy patients with unilateral disease by means of laser Doppler flowmetry (in perfusion units) and capillary microscopy. The patients were divided into three stages according to their perception of skin temperature (stage I in the case of a stationary warmth sensation, stage II in the case of an intermittent warmth and cold sensation, and stage III in the case of a stationary cold sensation). The vasoconstrictive responses were induced by lowering of the affected hand. 2. As compared to controls, the mainly sympathetically mediated vasoconstrictive response at thermoregulatory level of the skin microcirculation, as measured by laser Doppler flowmetry, was attenuated at stage I (1.82 versus 1.41, P < 0.05), stage II (1.82 versus 1.09, P < 0.0001) and stage III (1.82 versus 1.14, P < 0.01), suggesting the involvement of sympathetic denervation at all stages of the reflex sympathetic dystrophy syndrome. This sympathetic denervation may also account for the observed increase in thermoregulatory skin blood flow at stage I as compared to controls (152 versus 81, P < 0.01). 3. Since sympathetic denervation has been reported to cause increased sensitivity of vascular structures to catecholamines, the decrease in thermoregulatory skin blood flow at stages II (54 versus 81, P < 0.05) and III (31 versus 81, P < 0.05), both as compared to controls, may result from hypersensitivity to catecholamines of skin microvessels. 4. The sympathetically independent vasoconstrictive response at the nutritive level of skin microcirculation, as measured by capillary microscopy, was impaired only at stage III as compared to controls (1.04 versus 2.06, P < 0.05). This divergence in microvascular reactivity upon dependency of the nutritive and thermoregulatory subsystems also supports the hypothesis of sympathetic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874858 TI - Plasma atrial and brain natriuretic peptides in mitral stenosis treated by valvulotomy. AB - 1. In order to appreciate the effect of changes in left atrial pressure on plasma brain natriuretic peptide, 20 patients with mitral stenosis treated by percutaneous valvulotomy were studied 10 min before and 15 min after the first balloon inflation. They were also studied 24 h before and 48 h after the valvulotomy. At these times the effect of postural changes on brain natriuretic peptide secretion was examined. A group of 10 control subjects was also studied under basal conditions. In each case, plasma atrial natriuretic peptide was measured in parallel with plasma brain natriuretic peptide. 2. Similarly to plasma atrial natriuretic peptide, plasma brain natriuretic peptide was elevated in patients with mitral stenosis (32 +/- 2.9 and 32 +/- 2.8 pg/ml in the upright and supine position respectively versus 13.5 +/- 0.5 and 13.8 +/- 1.8 pg/ml in controls; P < 0.01). Changing from standing to lying did not modify plasma brain natriuretic peptide, whereas it produced an increase in plasma atrial natriuretic peptide in controls (13.3 +/- 1.6 versus 24.8 +/- 5.2 pg/ml; P < 0.01) and in patients 48 h after valvulotomy (52.5 +/- 4.6 versus 66.9 +/- 6.6 pg/ml; P < 0.01). Plasma brain natriuretic peptide also fell at this time (18.8 +/- 1.1 and 19.1 +/- 1.1 pg/ml in the upright and supine position respectively; P < 0.01) similarly to plasma atrial natriuretic peptide and cyclic GMP (P < 0.01). The acute left atrial mean pressure variation was significantly correlated with the parallel change in plasma atrial natriuretic peptide (P < 0.001) but not in plasma brain natriuretic peptide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874859 TI - Plasma natriuretic peptides and cardiac volume during acute changes in intravascular volume in haemodialysis patients. AB - 1. Plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptides (BNP) were measured, along with left and right atrial and left ventricular volumes, in eight patients with chronic renal failure before and after the removal of 2.1 +/- 0.61 of fluid by ultrafiltration and again during volume repletion with intravenous sodium chloride solution (150 mmol/l saline) to restore body weight plus 0.5 kg. 2. Baseline levels of ANP (46.0 +/- 7.5 pmol/l) and BNP (22.0 +/- 4.4 pmol/l) were elevated above normal. There was a significant reduction in plasma ANP (26.5 +/- 4.7 pmol/l, P < 0.05) and BNP (19.1 +/- 4.9 pmol/l, P < 0.05)) following ultrafiltration. Changes in plasma ANP during ultrafiltration correlated significantly with changes in left atrial volume (r = 0.643, P < 0.05). 3. During volume repletion there was an exaggerated release of ANP (mean level post repletion 71.3 +/- 20.8 pmol/l) which was not paralleled by changes in BNP. Changes in BNP were small, showing no correlation with atrial or ventricular volumes during either ultrafiltration or volume repletion. 4. These findings indicate that in chronic renal failure without left ventricular dysfunction, moderate acute changes in volume status elict only small immediate responses in plasma BNP. Changes in plasma ANP are greater than BNP and more responsive to changes in left atrial volume. PMID- 7874860 TI - An angiotensin converting enzyme inhibitor, perindopril, prevents progression of preformed atherosclerotic lesions in the cholesterol-fed rabbit. AB - 1. The aim was to determine whether the angiotensin converting enzyme inhibitor perindopril, at a concentration approaching that used in human antihypertensive therapy, influences progression of preformed atherosclerotic plaques. 2. Rabbits had their right carotid artery deendothelialized with a balloon catheter, which resulted in the formation of a myointimal thickening. 3. At 14 weeks post surgery groups I, II and III (n = 6 per group) were fed a 1% cholesterol-enriched diet for 6 weeks, then group I rabbits were sacrificed. Groups II and III were placed on a normolipidaemic diet for a further 6 weeks with group III rabbits also receiving 0.3 mg day-1 kg-1 perindopril. Groups IV and V were treated the same as groups II and III, respectively, except that they received a normal diet throughout. 4. Group I rabbits fed a 1% cholesterol-enriched diet for 6 weeks developed lipid-filled lesions covering 26.3 +/- 14.3% of the surface area of the descending thoracic aorta. This was exacerbated in rabbits fed a 1% cholesterol diet for 6 weeks followed by 6 weeks on a normal diet (61.2 +/- 27.3%). In rabbits fed a 1% cholesterol diet for 6 weeks than a normal diet for a further 6 weeks plus 0.3 mg day-1 kg-1 perindopril, the percentage surface area covered by lesions was 21.8 +/- 15.8%. No lesions developed in the aortas of rabbits fed a normal diet. In the right coronary artery the resulting neointima in rabbits fed a 1% cholesterol diet for 6 weeks only was 42.4 +/- 5.7% of the cross-sectional area of the vessel wall, 57.4 +/- 8.0% in rabbits receiving 6 weeks' cholesterol diet than 6 weeks' normal diet, 36.0 +/- 6.6% in rabbits fed a 6-week cholesterol diet than 6 weeks' normal diet with 0.3 mg day-1 kg-1 perindopril and 33.2 +/- 4.9% and 31.8 +/- 3.1% in rabbits on a normal diet throughout with 0 and 0.3 mg day-1 kg-1 perindopril respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7874861 TI - Alpha 1-antitrypsin phenotypes in patients with anti-neutrophil cytoplasmic antibody-positive vasculitis. AB - 1. The genetic background of anti-neutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis remains largely unknown. Recently a very high prevalence of medium and severe deficiency of alpha 1-antitrypsin was described in a small group of patients with Wegener's granulomatosis and c-ANCA. c-ANCAs are autoantibodies against proteinase 3, and alpha 1-antitrypsin is the main inhibitor of this enzyme. 2. alpha 1-Antitrypsin phenotypic polymorphism was determined by isoelectric focusing in 32 patients with c-ANCA-associated systemic vasculitis. Twenty-nine patients had Wegener's disease, two had microscopic polyarteritis and one suffered from idiopathic rapidly progressive glomerulonephritis. 3. Two patients were homozygous PiZZ and three were heterozygous PiMZ. These phenotype frequencies differed significantly from expected values, assuming Hardy-Weinberg equilibrium (P < 0.01). Compared with a control group of 868 healthy blood donors, these results meant a significant increase in the PiZ allele (0.0138 versus 0.1094, P < 0.001). 4. Furthermore, the serum of 47 patients with severe alpha 1-antitrypsin deficiency (PiZZ) was tested for the presence of ANCA. All sera were negative for c-ANCA and p-ANCA. None of the patients showed clinical signs of systemic vasculitis. 5. In conclusion, these data indicate that alpha 1-antitrypsin deficiency, despite being significantly more common in patients with c-ANCA-associated systemic vasculitis, is only a minor genetic risk factor for the development of this disease. PMID- 7874862 TI - Effects of fasting on fatty acid kinetics and on the cardiovascular, thermogenic and metabolic responses to the glucose clamp. AB - 1. The effects of fasting for 12, 36 and 72 h were examined in 19 normal subjects. Each subject was studied before and during a euglycaemic (4 mmol/l) hyperinsulinaemic (100 m-units min-1 m-2) clamp. Measurements were made of palmitate turnover and oxidation, glucose disposal, thermogenesis, intermediary metabolites and cardiovascular variables. 2. Basal respiratory exchange ratio fell from 0.78 +/- 0.01 to 0.75 +/- 0.01 to 0.72 +/- 0.01 with fasting (P < 0.001). In response to the clamp it rose to 0.91 +/- 0.02, 0.83 +/- 0.01 and 0.77 +/- 0.01 after 12, 36 and 72h respectively. Metabolic rate rose during the clamp by 0.41 +/- 0.06, 0.11 +/- 0.03 and 0.14 +/- 0.04 kJ/min respectively (P < 0.001 for 36- and 72-h values versus that at 12h). 3. Fasting reduced total insulin mediated glucose disposal rates from 42.6 +/- 2.5, to 31.0 +/- 1.8 to 21.3 +/- 1.5 mumol min-1 kg-1 body weight after 12, 36 and 72h respectively (P < 0.001). Glucose oxidation fell from 16.9 +/- 1.1 to 8.7 +/- 1.7 to 0.2 +/- 1.3 mumol min 1 kg-1 body weight over the same period (P < 0.001). Non-oxidative glucose disposal rates did not change significantly. 4. Basal plasma palmitate turnover increased with duration of fasting, being 1.16 +/- 0.08, 1.72 +/- 0.17 and 2.30 +/- 0.35 mumol min-1 kg-1 body weight. In response to the clamp, palmitate turnover fell to 0.42 +/- 0.05, 0.69 +/- 0.08 and 1.28 +/- 0.45 mumol min-1 kg-1 body weight. Plasma palmitate oxidation was 0.58 +/- 0.04, 0.75 +/- 0.06 and 1.13 +/- 0.11 mumol min-1 kg-1 body weight basally, and fell to 0.16 +/- 0.02, 0.28 +/ 0.04 and 0.43 +/- 0.13 mumol min-1 kg-1 body weight by the end of the clamp. The proportion of total lipid oxidation represented by plasma non-essential fatty acid oxidation was not affected by fasting, but fell in response to the clamp. 5. Fasting caused a progressive resistance to the effects of insulin and glucose on oxidative glucose disposal and on forearm glucose uptake. Insulin-mediated glucose storage was unaffected by fasting, but the apparent cost of this storage was reduced by fasting. PMID- 7874863 TI - Effect of oral creatine supplementation on respiratory gas exchange and blood lactate accumulation during steady-state incremental treadmill exercise and recovery in man. AB - 1. Oral creatine supplementation has been shown to increase muscle creatine and phosphocreatine concentrations with consequent benefits on performance during short-term maximal exercise. However, recently there have been anecdotal reports that creatine supplementation can also influence the pattern of substrate utilization and improve performance during more prolonged, submaximal exercise, which, based on recent experimental evidence, may have some scientific justification. 2. Eight men performed a continuous incremental exercise test running at 10 km/h on a motorized treadmill at predetermined workloads from 50% to 90% of maximal oxygen uptake, before and after 5 days of creatine supplementation (4 x 5 g daily). Exercise was performed for 6 min at each workload to achieve a steady state, and respiratory gas exchange and blood lactate concentrations were measured during the last 30 s at each workload. Measurements were also made at 5-min intervals for the first 15 min of recovery. 3. The results showed no measurable effect of creatine supplementation on respiratory gas exchange and blood lactate concentrations during either incremental submaximal exercise or recovery. This suggests that creatine supplementation does not influence substrate utilization during and after this type of exercise. PMID- 7874864 TI - Modulation of cytokine production in vivo by dietary essential fatty acids in patients with colorectal cancer. AB - 1. The effects of essential fatty acids (gamma-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid), at a dose of 4.8 g/day, given in combination as dietary supplements, on cytokine production were investigated in patients with colorectal cancer. 2. Total serum cytokines--interleukin (interleukin-1 beta, 2, 4 and 6), tumour necrosis factor-alpha and interferon-gamma--were analysed using the enzyme-linked immunosorbent assay technique at different time intervals during the course of essential fatty acid supplementation. 3. Fatty acid uptake and patient compliance were confirmed by a significant increase in serum levels of gamma-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid in all three fractions: tricylglycerol, cholesterol and phospholipid. 4. There was no significant alteration in total serum cytokine concentration/levels in the first 2 months of essential fatty acid ingestion, but the levels of serum cytokines steadily declined thereafter, reaching minimum levels after 6 months of essential fatty acid supplementation. 5. Essential fatty acids, at the dose and duration (6 months) used in this study, reduced total serum interleukin-1 beta levels by 61% (P = 0.044), interleukin-2 by 63% (P = 0.05), interleukin-4 by 69% (P = 0.025), interleukin-6 by 83% (P = 0.030), tumour necrosis factor-alpha by 73% (P = 0.040) and interferon-gamma by 67% (P = 0.050). 6. Three months after cessation of essential fatty acid intake, however, these cytokine levels returned to presupplementation values. 7. This present study has shown that long-term n-3 and n-6 EFA ingestion results in a significant reduction in circulating key cytokines. The precise mechanism of this reduction is unclear. PMID- 7874865 TI - Interaction of polyacrylates with porcine pepsin and the gastric mucus barrier: a mechanism for mucosal protection. AB - 1. The mechanism of interaction of the polyacrylates, carbopols with the mucus barrier in vivo has been investigated in vitro. 2. Carbopol caused a dramatic increase in the viscosity of porcine gastric mucin solutions that was up to 19 fold greater than that of the sum of the individual polymers. 3. The mucin carbopol interaction was stable after an initial 30 min period for up to 36 h at 25 degrees C or 37 degrees C. It was reduced by increasing the temperature from 20 degrees C to 45 degrees C, was unaffected by pH and ionic strength, but was enhanced by Ca2+. 4. The magnitude of the interaction between mucin and carbopol depended on the polymeric structure of the mucin and the molecular size and level of cross-linking of the carbopol. 5. The interactions were reversible and increased with increasing carbopol and mucin concentration. The dramatic increase in viscosity can be explained in terms of space filling by the mucin molecules leading to predominantly carbopol-carbopol interactions. 6. Carbopol 934P inhibits pepsin hydrolysis and therefore has potential as a mucosal protective agent in vivo. PMID- 7874866 TI - Renal and cardiac complications of hypertension. PMID- 7874867 TI - Physiology of hemostasis. AB - The consequences of acute insults to the hemostatic system, whether congenital or acquired, frequently present a considerable challenge in diagnosis and therapy. Logical and effective management depends upon the proper identification of the hemostatic compartments involved; an appreciation for the considerably complex, delicately modulated interplays of various enzyme/inhibitor systems; and knowledge of the mechanism by which a variety of apparently unrelated disease processes precipitate sometimes catastrophic events- thrombosis/embolism/hemorrhage. We have attempted a logical review of basic mechanisms of hemostasis. The text is obligatorily brief, focusing on key elements of the biochemistry and physiology of the vessel wall, the platelet, and pertinent plasma factors. The section on plasma proteins pays particular attention to biocybernetic principles (positive/negative feedback loops) and to the interrelationship of enzyme systems involved in coagulation, fibrinolysis, kinin generation, and complement activation. No attempt was made to be encyclopedic. In the interest of brevity and clarity, the text has been limited to current concepts, with the reference material selected, whenever possible, in the form of review articles, volumes and monographs. We apologize for omissions. It is our belief that a working knowledge of basic mechanisms provides not only advantages in diagnostic/therapeutic management but also serves as a firm foundation for the development of novel diagnostic and therapeutic modalities. PMID- 7874868 TI - Automation and quality control in the coagulation laboratory. AB - Hemostasis is a balance between complex interactions of directly opposing systems (coagulation and fibrinolysis) with seemingly unrelated systems at both the enzymatic and cellular levels (platelets, endothelium, leukocytes). It should not be surprising that coagulation disorders often accompany many different disease states. Because the function of each protein involved in coagulation is now better defined, newer methodologies have been developed to assay them. In this regard, the hemostasis laboratory can take a two-step approach to diagnosis: global screening and targeted analysis. Several new global test systems provide more detailed, quantitative, and more physiologically relevant evaluations than earlier assays allowed. In addition, individual enzymes, inhibitors, cellular release products, and low molecular weight products of activation reactions (molecular markers) can now be measured in sensitive, specific assays. With this new perspective, genetic predisposition to pathologic hemostatic conditions can be identified through molecular biology and can be identified during the early stages of disease (i.e., at subclinical stages before major pathologic complications are established), and more specifically targeted prophylactic, as well as therapeutic drug interventions, can be administered. The molecular markers of hemostatic activation that can be assessed by various immunochemical methods provide very early evidence of thrombotic, fibrinolytic, or platelet involved aberrations. Technological advances in methodology and instrumentation have changed the scope of all clinical laboratories but, in particular, that of the coagulation laboratory. The dramatic growth and development have resulted from the influences of clinical chemistry, clinical immunology, pharmacology, biochemistry, and biotechnology. Analytical instruments for use in hemostatic testing go beyond plasma or whole blood clot-based readers, platelet aggregometers, and microscopes to a range of automated, discrete, chemistrylike analyzers, spectrophotometers, microliter ELISA systems, RIA systems, and multiprobe instruments designed to measure simultaneously the different assay end points of colorimetric and clotting assays and flow cytometers. Instruments are designed for batch processing of single tests on multiple samples or multiple test panels on a single sample. Versatility ranges from instruments that measure only the final reaction solution, by end-point or kinetic analysis, to instruments that automatically pipet reagents and sample, incubate, and analyze the reaction for truly walk-away assay performance. Typically, a wider range of assays are available in automated laboratories as opposed to laboratories performing manual assays.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7874869 TI - Disseminated intravascular coagulation. Objective laboratory diagnostic criteria and guidelines for management. AB - Current concepts of the etiology, pathophysiology, clinical and laboratory diagnosis, and management of fulminant and low-grade DIC have been presented. Considerable attention has been devoted to interrelationships within the hemostasis system. Only by clearly understanding these pathophysiological interrelationships can the clinician and laboratory scientist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. In this discussion, objective clinical and laboratory criteria for the diagnosis of DIC have been delineated, thus eradicating needless confusion and empirical decisions regarding the diagnosis. Many therapeutic decisions to be made are controversial and will remain so until more is published about specific therapeutic modalities and survival patterns. Also, therapy must be highly individualized depending on the nature of DIC, age, etiology of DIC, site and severity of hemorrhage or thrombosis, and hemodynamic and other clinical parameters. Also presented are clear criteria for the severity of DIC and objective criteria for defining a response to therapy. Because it frequently is difficult for the individual physician to decide when to stop often extensive and expensive therapy, objective criteria whereby therapy may be stopped, as it is deemed that continuation is most likely fruitless, have been presented as a guideline. Many syndromes, which frequently are organ-specific, share common pathophysiology with DIC but are typically identified as an independent disease entity, for example, hemolytic uremic syndrome, adult shock-lung syndrome, eclampsia, and many other isolated organ-specific disorders. PMID- 7874870 TI - Coagulopathies of liver disease. AB - Disturbed liver parenchymal cell function adversely impacts on the hemostasis system, the extent of which correlates with the degree of liver disease. Because liver parenchymal cells synthesize most factors of the clotting and the fibrinolytic systems, levels of these procoagulant and anticoagulant as well as profibrinolytic and antifibrinolytic factors will decrease in plasma. These changes may be minor in patients with mild liver disease but are severe in patients with cirrhosis. Thrombocytopenia and thrombocytopathy usually complicate the clinical presentation, and systemic activation of the fibrinolytic system is always seen in cirrhotic individuals. Whether this fibrinolytic activation is primary or secondary in response to DIC is controversial. Some of the laboratory findings in DIC may be a reflection of decreased hepatic clearance of activation products by the reticuloendothelial system of the diseased liver. In patients with vitamin K deficiency or in those receiving oral anticoagulants, only the vitamin K-dependent procoagulants and anticoagulants are altered; all other parameters remain in the normal range. Laboratory changes associated with various surgical interventions involving the liver depend on the underlying pathology. Severe hemorrhages are encountered during orthotopic liver transplantation. During the anhepatic phase and during the reperfusion phase, there is a major activation of the fibrinolytic system. It is unclear whether this fibrinolytic response is primary or secondary. The use of antifibrinolytic agents has markedly reduced the clinical bleeding and, thus, the requirement for blood and blood products. Bleeding associated with partial liver resection is usually mechanical in nature, but peritoneovenous shunt operations can result in DIC. Ascites fluid is the trigger. The injection of thrombin containing sclerosants can also activate the hemostasis system in vivo, although, generally, no clinically detectable adverse reactions are noted. PMID- 7874871 TI - Laboratory diagnosis of von Willebrand's disease. AB - The diagnosis of von Willebrand's disease is becoming complex as more is understood about the disease. Clinical information and laboratory data are necessary for the diagnosis because of the overlap of normal and abnormal laboratory values. A complete evaluation including von Willebrand factor multimers, ristocetin-induced platelet aggregation, factor VIII activity level, and a template bleeding time is necessary to correctly classify the patient so that optimal treatment may be given. PMID- 7874872 TI - Laboratory assessment of circulating anticoagulants. AB - Circulating anticoagulants pose challenging conceptual, technical, and interpretive problems in the laboratory. Their sound diagnosis and management depend on a clear understanding of both the in vivo and in vitro manifestations of the three classes of inhibitors (nonspecific, multispecific, and specific) and the entities therein. From the ongoing research, this field will undoubtedly continue to grow in significance and complexity, demanding ever greater laboratory expertise and competence. PMID- 7874873 TI - Laboratory monitoring of oral anticoagulant therapy. AB - The safety and success of oral anticoagulant treatment are dependent on laboratory control by the prothrombin time test. Until recently, the therapeutic range in prothrombin ratios of 2.0 to 2.5 resulted in greatly different dosage regimes, because of the lack of standardization of the test, particularly its thromboplastin component. Low-dose warfarin was associated with responsive thromboplastin. In North America and many other countries, a high-dose regime from high international sensitivity index thromboplastin caused more bleeding. PMID- 7874874 TI - Laboratory monitoring of new antithrombotic drugs. AB - This article examines laboratory methods that are used or may be used to monitor newly developed heparins, low-dose vitamin K antagonists, new thrombin inhibitors such as recombinant hirudin, and oligopeptide thrombin inhibitors (some of which it is hoped will be orally active), thromboxane receptor antagonists, glycoprotein IIb-IIIa inhibitors, and ticlopidine-like structures. PMID- 7874875 TI - Argument structure and association preferences in Spanish and English complex NPs. AB - Three questionnaire studies investigated Spanish and English readers' interpretations of sentences with complex noun phrases (NPs) such as "I really liked the preface of the book that I read yesterday." These complex NPs are ambiguous between two readings, one in which the relative clause (RC) that I read yesterday modifies the first noun, N1, preface, or the second noun, N2, book. Cuetos and Mitchell (Cognition, 1988, 30, 73-105) claimed that Spanish was biased toward having the RC modify N1, which they claimed was evidence against the cross language universality of the late closure parsing principle. We demonstrate that the preference for N1 versus N2 modification varies greatly between different construction types within both Spanish and English while the variation between languages is relatively minor, but still of interest. The effect cannot be reduced to an effect of plausibility, but seems to reflect directly certain syntactic and semantic aspects of the constructions studied. We claim that relative clauses and other "nonprimary" phrases are not parsed following such parsing principles as late closure, but instead follow principles we advance in the form of the construal hypothesis. Thus, it is not the case that late closure is a language-specific strategy; rather, it and similar structural parsing principles are specific to only certain classes of phrases within a language. PMID- 7874876 TI - A crosslinguistic comparison of the production of utterances in discourse. AB - Functionalist theorists have proposed a number of decisions that a speaker has to make regarding the packaging of messages in response to the knowledge shared by the speaker and the listener in a discourse situation. The present study examined some procedures used by French and English speakers to implement message packaging during sentence formulation. The speech of French and English students talking informally about topics of interest to them was recorded, and hesitations were identified and located in the speech. According to the hesitation data, like English speakers, French speakers organised their thoughts into successive units having a variety of structural characterisations. Sentences, surface clauses, basic clauses and phrases were all found to be output units. In addition, French as well as English speakers output clauses containing new information more independently than clauses either containing presupposed information or satisfying an essential argument of the verb. French speakers also differed from English speakers in several ways. During articulation, phrases acted as more tightly integrated output units for French than for English speakers. French speakers also used different syntactic devices from English speakers for introducing and focussing on topics in the discourse. They did this by means other than the use of lexical subjects, such as left-detached topics and cleft sentences, supporting the hypothesis that spoken French has topic-comment structure, while English has subject-verb-object organisation. The crosslinguistic differences were argued to result largely from the distinct prosodic characteristics of the languages. The results were seen as providing new evidence for the similar and contrasting ways in which speakers of different languages respond to decisions about message packaging. PMID- 7874877 TI - Do children have a theory of race? AB - In recent years a number of studies have detailed young children's enriched, domain-specific, and theory-like understanding in several cognitive domains, including naive biology, naive psychology, and reasoning about physical objects. With few exceptions, students of cognition have not considered the possibility that the acquisition and representation of social categories may also be governed by a specialized faculty for understanding. Rather, most accounts of children's social categorization assume that the classification of the human realm is derived from observations of superficial differences in appearance and does not include expectations of deeper commonalities among category members. Five experiments are reported that challenge this view. The results indicate that young children's inferences about human racial variation involve domain-specific reasoning that parallels but is distinct from common sense understanding of naive biology. These findings have implications for our understanding of the transfer of knowledge across domains and for determining the appropriate level of description of domain-specific devices. PMID- 7874878 TI - Subcultures of BACTEC-positive but gram or acridine orange stain-negative NR 6A and 7A blood culture bottles are unnecessary. AB - A prospective study was done to assess the comparative use of acridine orange and Gram stains for detecting false-positive BACTEC blood culture bottles, thereby eliminating unnecessary subcultures. A total of 1049 NR 6A and 7A bottles that were instrument-positive in the BACTEC 660 nonradiometric system, but were Gram stain-negative, had aerobic and anaerobic subcultures as well as an acridine orange stain performed. Only five of 1049 (0.5%) instrument-positive, Gram stain negative bottles grew microorganisms on subculture. Of these five microorganisms, acridine orange stain detected two. All five microorganisms were assessed not to be clinically significant based on review of the patients' charts. Our data showed that the Gram stain and the acridine orange stain are comparable for detecting false-positive NR 6A and 7A bottles. We conclude that subculture of BACTEC-positive, Gram stain-negative NR 6A and 7A bottles is not necessary. PMID- 7874879 TI - Strain delineation and antifungal susceptibilities of epidemiologically related and unrelated isolates of Candida lusitaniae. AB - Candida lusitaniae is an important nosocomial pathogen that may express resistance to one or more antifungal agents including amphotericin B. We investigated the genotypic diversity and antifungal susceptibility among 47 clinical isolates from 33 patients hospitalized in 12 different medical centers. Strain delineation was performed by restriction endonuclease analysis of genomic DNA (REAG) with the restriction enzyme Sfi I followed by pulsed-field gel electrophoresis and by electrophoretic karyotyping (EK). Antifungal susceptibility of the isolates to amphotericin B, 5-fluorocytosine (5FC), fluconazole, and itraconazole was determined using National Committee for Clinical Laboratory Standards standard methods. Minimum inhibitory concentration (MIC)90 values ranged from 0.5 micrograms/ml for itraconazole to 512 micrograms/ml for 5FC. In general, isolates from a given patient or epidemiologically related isolates from a nosocomial cluster were identical by molecular typing methods. Epidemiologically unrelated isolates were all distinctly different by both EK and REAG typing methods. Although elevated amphotericin B MICs ( > or = 2 micrograms/ml) were observed in only three isolates, extended incubation (72 h) revealed amphotericin B MICs of 2-16 micrograms/ml in a subset of isolates suggesting potential amphotericin B resistance. These data document the genetic diversity, nosocomial transmission, and antifungal susceptibility of clinical isolates of C. lusitaniae. PMID- 7874880 TI - Major methodology-dependent discordant susceptibility results for Bacteroides fragilis group isolates but not other anaerobes. AB - Two standardized susceptibility test methods, a broth microdilution (BMD) and agar dilution (AD) method were performed on a total of 441 clinical isolates of anaerobes with ceftizoxime, cefotaxime, ceftriaxone, cefoxitin, piperacillin, and metronidazole. Against the 339 strains of the Bacteroides fragilis group BMD minimum inhibitory concentration (MIC) values were lower than those from AD testing for all the beta-lactams. Overall for the B. fragilis group and the beta lactams, the mode MIC values were two- to 64-fold lower, and the MIC50 values two to eightfold lower. Resistance rates were 11%-28% higher overall with AD results and were higher especially for non-B. fragilis species. For non-Bacteroides anaerobes no major discrepancies were noted for Prevotella species, Peptostreptococcus species, and Viellonella parvula. With Clostridium species and Eubacterium species, some differences were noted with ceftizoxime because of differences in cut-off points. These data illustrate the magnitude of differences in results produced by the two methods using essentially the same test medium for the B. fragilis group. Fortunately, such major discordant results were not widely noted with other groups of anaerobes. PMID- 7874881 TI - Prediction of piperacillin-tazobactam susceptibility among Enterobacteriaceae, Pseudomonas aeruginosa, and other bacteria using ticarcillin-clavulanic acid, ceftazidime, and other broad-spectrum antimicrobial in vitro test results. AB - The ability of various in vitro beta-lactam susceptibility test results to predict the susceptibility of piperacillin-tazobactam (a new beta-lactam-beta lactamase inhibitor combination) was assessed using more than 46,000 recent clinical isolates. The organisms were tested by reference-quality National Committee for Clinical Laboratory Standards (NCCLS) broth microdilution procedures and interpreted by the currently published NCCLS criteria. The recommended antimicrobial tests that would accurately predict the piperacillin tazobactam in vitro efficacy had an overall very major, false-susceptible rate of only 0.6% (< or = 1.5% is acceptable). The following drug tests can be used to judge piperacillin-tazobactam activity and spectrum (low patient risk) conservatively: for Enterobacteriaceae use ticarcillin-clavulanic acid results (0.6% very major error); for Pseudomonas aeruginosa use piperacillin (0.1%) results; for enterococci use ampicillin or ampicillin-sulbactam (1.8%) results; for Haemophilus influenzae and Moraxella catarrhalis use cefotaxime or cefuroxime or ceftriaxone (1.5%); and for staphylococci use oxacillin by NCCLS recommendations. When the piperacillin-tazobactam testing reagents become available, the direct testing of this combination should be applied to relevant clinical isolates. The piperacillin-tazobactam break points should be reassessed as indicated by the cited minimum inhibitory concentration population analysis to improve predictive accuracy; H. influenzae susceptibility modified to < or = 2/4 micrograms/ml and Enterococcus species susceptibility tested at < or = 16/4 micrograms. PMID- 7874882 TI - Antimicrobial susceptibility patterns of bacterial isolates at the American University Medical Center in Lebanon. AB - In Lebanon, knowledge of the prevailing pattern of bacterial resistance to antimicrobial agents has been limited, particularly because of 15 years of civil strife. Thus, the current study was conducted to determine the antimicrobial susceptibility patterns of nonselected bacterial isolates recovered from recent clinical specimens, using the standardized disk agar diffusion technique. A total of 5216 isolates (1443 Gram positive and 3773 Gram negative) were examined. Over 92% of Staphylococcus aureus and coagulase-negative staphylococci (CNS) were resistant to penicillins. Methicillin resistance was more frequently noted among CNS (28%) compared with S. aureus (18%). For the pneumococci, 27% of the isolates were resistant to penicillin G. High but variable rates of multidrug resistance were encountered among Acinetobacter spp., Pseudomonas spp., Serratia spp., Citrobacter spp., and Enterobacter spp. Ampicillin resistance was detected in 65% of Escherichia coli and in 20% of Haemophilus influenzae isolates. Although one resistant Salmonella typhi strain was observed, 17% of other Salmonella spp. and 60% of Shigella spp. proved to be resistant to ampicillin, chloramphenicol, and cotrimoxazole. Among Vibrio cholerae isolates, high resistance to tetracycline (71%) and trimethoprim-sulfamethoxazole (94%) was observed. The overall antimicrobial resistance rates in Lebanon seem to fall between figures reported from the Arabian Gulf countries (higher) and those from medical centers in the United States (lower). PMID- 7874883 TI - Evaluations of the Etest for antimicrobial susceptibility testing of Legionella pneumophila, including validation of the imipenem and sparfloxacin strips. AB - Development of antimicrobial testing for Legionella spp. has been technically compromised by the fastidious growth requirements of this organism and by the most commonly used medium, buffered charcoal yeast extract agar (BCYE) that contains substances known to inhibit some antimicrobial agents. This study validated the potency of two newer antimicrobials (sparfloxacin and imipenem) and their Etest strip. The comparisons of antimicrobial minimum inhibitory concentration (MIC) values as determined by Etest on BCYE agar (98 Legionella pneumophila) demonstrated that sparfloxacin was the most potent drug (MIC90, 0.19 microgram/ml) among the fluoroquinolones, macrolides, tetracyclines, and beta lactams tested. Imipenem MICs (MIC90, < or = 0.38 microgram/ml) were also determined by a reference agar dilution method and validated Etest strips on buffered yeast extract agar, buffered charcoal yeast extract agar, and buffered charcoal yeast extract agar with defined supplements. The non-Legionella control strains used to demonstrate medium component influences on the imipenem MICs demonstrated the addition of supplements (particularly L-cysteine) markedly elevated the MICs. These data indicate that the Etest was a simple and accurate quantitative method for susceptibility tests with Legionella isolates. Sparfloxacin among the fluoroquinolones and imipenem among the beta-lactams require further clinical studies for legionellosis therapy. PMID- 7874884 TI - Extragenital infection due to Mobiluncus mulieris. Case report and review. AB - Mobiluncus species are uncommonly isolated from nongenital sites. We report a case of abdominal abscess with associated Mobiluncus mulieris bacteremia and review the literature on extragenital infections due to Mobiluncus species. PMID- 7874885 TI - Preliminary interpretive criteria for in vitro susceptibility testing of CP-99219 by dilution and disk diffusion methods. AB - CP-99219 is a novel 7-[3-azabicyclo (3.1.0) hexyl] quinolone that possesses activity against a wide variety of aerobic and anaerobic pathogens. The disk diffusion test results (5-micrograms CP-99219 disks) were compared with CP-99219 minimum inhibitory concentrations (MICs) using 445 contemporary clinical isolates, including 210 strains that were resistant to ciprofloxacin (MICs, > or = 4 micrograms/ml). A high correlation was observed between methods (r = 0.97), and the proposed conservative zone diameter interpretive criteria were selected primarily from the regression equation as follows: susceptible at > or = 15 mm (< or = 2 micrograms/ml, preferred) and resistant at < or = 10 mm (> or = 8 micrograms/ml); or susceptible at > or = 19 mm (< or = 1 microgram/ml) and resistant at < or = 14 mm (> or = 4 micrograms/ml). Using these criteria, the occurrence of false-resistant and false-susceptible disk diffusion test results should remain rare (< or = 1.5%). PMID- 7874886 TI - Comparison of mupirocin susceptibility of nasal and nonnasal Staphylococcus aureus isolates. AB - Susceptibilities of 414 nasal and 586 nonnasal Staphylococcus aureus isolates, both methicillin resistant and methicillin susceptible, to the topical antimicrobial agent mupirocin were compared. A susceptibility of 99.1% was observed for the 1000 isolates. Nasal and nonnasal isolates showed a similar 90% minimum inhibitory concentration (MIC90) and statistically equivalent percent susceptibilities. PMID- 7874887 TI - In vitro activity of FK-037. A parenteral cephalosporin. AB - The in vitro activity of FK-037, a new extended spectrum cephalosporin, was determined against 398 recent clinical isolates consisting of ceftazidime susceptible and -resistant, aerobic Gram-negative rods, penicillin-susceptible and resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, methicillin-susceptible S. aureus, methicillin-susceptible coagulase negative staphylococci, and methicillin-resistant coagulase-negative staphylococci. Comparative drugs included ceftazidime, imipenem, and amikacin. Susceptibility testing was performed using a broth microdilution method. FK-037 showed greater activity than ceftazidime against ceftazidime-susceptible, aerobic Gram-negative rods. FK-037 showed enhanced activity compared with ceftazidime against Gram-positive organisms, including penicillin-resistant S. pneumoniae. Mutational frequencies for representative Gram-negative rods were comparable for FK-037 and ceftazidime. PMID- 7874888 TI - Neuromuscular blocking agents in the intensive care unit: a two-edged sword. PMID- 7874889 TI - Transplantation: patient survival and economic viability. PMID- 7874890 TI - Bicarbonate in cardiac arrest: the good, the bad, and the puzzling. PMID- 7874891 TI - Teaching medical students in the intensive care unit: an idea whose time has come -or gone? PMID- 7874892 TI - Neurologic critical care and the management of severe head injury in the United States. PMID- 7874893 TI - Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial. AB - OBJECTIVE: To determine if early enteral feeding, in an intensive care unit (ICU) patient population, using a formula supplemented with arginine, dietary nucleotides, and fish oil (Impact), results in a shorter hospital stay and a reduced frequency of infectious complications, when compared with feeding a common use enteral formula (Osmolite.HN). DESIGN: A prospective, randomized, double-blind, multicenter trial. SETTING: ICUs in eight different hospitals. PATIENTS: Of 326 patients enrolled in the study, 296 patients were eligible for analysis. They were admitted to the ICU after an event such as trauma, surgery, or sepsis, and met a risk assessment screen (Acute Physiology and Chronic Health Evaluation II [APACHE II] score of > or = 10, or a Therapeutic Intervention Scoring System score of > or = 20) and study eligibility requirements. Patients were stratified by age (< 60 or > or = 60 yrs of age) and disease (septic or systemic inflammatory response syndrome). INTERVENTIONS: Patients were enrolled and full-strength tube feedings were initiated within 48 hrs of the study entry event. Enteral feedings were advanced to a target volume of 60 mL/hr by 96 hrs of the event. One hundred sixty-eight patients were randomized to receive the experimental formula, and 158 patients were randomized to receive the common use control formula. MEASUREMENTS AND MAIN RESULTS: Both groups tolerated early enteral feeding well, and the frequency of tube feeding-related complications was low. There were no significant differences in nitrogen balance between groups on study days 4 and 7. Patients receiving the experimental formula had a significant (p = .0001) increase in plasma arginine and ornithine concentrations by study day 7. Plasma fatty acid profiles demonstrated higher concentrations of linoleic acid (p < .01) in the patients receiving the common use formula and higher concentrations of eicosapentaenoic and docosahexaenoic acid (p < .01) in the patients receiving the experimental formula. The mortality rate was not different between the groups and was significantly (p < .001) lower than predicted by the admission severity scores in both feeding groups. In patients who received at least 821 mL/day of the experimental formula, the hospital median length of stay was reduced by 8 days (p < .05). In patients stratified as septic, the median length of hospital stay was reduced by 10 days (p < .05), along with a major reduction in the frequency of acquired infections (p < .01) in the patients who received the experimental formula. In the septic subgroup fed at least 821 mL/day, the median length of stay was reduced by 11.5 days, along with a major reduction in acquired infections (both p < .05) in the patients who received the experimental formula. CONCLUSIONS: Early enteral feeding of the experimental formula was safe and well tolerated in ICU patients. In patients who received the experimental formula, particularly if they were septic on admission to the study, a substantial reduction in hospital length of stay was observed, along with a significant reduction in the frequency of acquired infections. PMID- 7874894 TI - Double-blind, randomized, multicenter study of doxacurium vs. pancuronium in intensive care unit patients who require neuromuscular-blocking agents. AB - OBJECTIVE: To compare the neuromuscular-blocking and hemodynamic effects of doxacurium vs. pancuronium administered by intermittent bolus to intensive care unit (ICU) patients who required neuromuscular block to facilitate mechanical ventilation for > or = 24 hrs. DESIGN: A multicenter, prospective, double-blind, randomized study comparing doxacurium, a new benzylisoquinolone neuromuscular blocking agent, with pancuronium. SETTING: ICUs of three tertiary care hospitals. PATIENTS: Forty critically ill patients (29 male, 11 female) with an average age of 52.5 yrs (range 19 to 80). INTERVENTIONS: With approval of our Institutional Review Boards and after obtaining informed consent, 40 critically ill patients were entered into the study. Histories and the results of physical examinations were recorded, laboratory data were collected, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated during the 8 hrs before the start of the study medication. Patients received either doxacurium (initial dose of 0.04 mg/kg) or pancuronium (initial dose of 0.07 mg/kg) by bolus injection with continuous measurement of vital signs every minute for 15 mins. We measured the degree of neuromuscular blockade using a peripheral-nerve stimulator to measure the Train-of-Four count. Patients were rebolused (doxacurium dose of 0.025 mg/kg, pancuronium dose of 0.05 mg/kg) based on clinical criteria, which were substantiated by measurement of the Train-of-Four count. The neuromuscular blocking drugs were stopped when the patient no longer required paralysis or after 5 days of therapy, whichever came first. Group comparisons were made using repeated measures analysis of variance, Fisher's exact test, and two sample t tests, when appropriate. Spearman's rank-correction coefficients were calculated to assess the relationship of onset time and recovery time with all baseline laboratory values and the APACHE II scores. A p < .05 was used to establish statistical significance. MEASUREMENTS AND MAIN RESULTS: There were no differences between the two groups with respect to age, gender, or APACHE II scores. There were no differences between groups in terms of adverse experiences, nor with respect to time of onset of block, number of doses, or the duration of neuromuscular blockade (2.6 vs. 2.2 days for doxacurium vs. pancuronium, respectively). There was a statistically significant increase in heart rate after the initial dose of pancuronium (120 +/- 23 vs. 109 +/- 22 beats/min postinjection vs. preinjection, respectively; p < .05) without any differences noted after doxacurium (107 +/- 21 vs. 109 +/- 21 beats/min, respectively). Furthermore, once neuromuscular block was discontinued, the pancuronium group had a more prolonged and variable recovery time (279 +/- 229 mins) compared with the doxacurium group (138 +/- 46 mins, p < .05). CONCLUSIONS: In critically ill patients requiring neuromuscular block for > 24 hrs, doxacurium was well tolerated without evidence of tachycardia and with a relatively prompt recovery profile. PMID- 7874895 TI - Effect of sepsis on erythrocyte intracellular calcium homeostasis. AB - OBJECTIVES: To examine erythrocyte intracellular calcium dynamics in clinical sepsis and experimental endotoxemia. DESIGN: Prospective, multiexperimental study utilizing in vitro manipulation and evaluation of human erythrocytes. SETTING: University research laboratory. PATIENTS: Healthy, elective surgical patients, "septic" surgical patients, and normal volunteers. INTERVENTIONS: For all experimental studies, whole blood specimens were incubated with 2 micrograms/mL of Escherichia coli endotoxin (experimental) or an equivalent volume of phosphate buffered saline (control). Incubations were performed in specimens pretreated with 0.4 mM of verapamil and/or 50 mM of dantrolene. Incubations were performed in the presence and absence of extracellular calcium. Incubations were also performed utilizing pre- and posttreatment with 1 mM of adenosine 5'-triphosphate (ATP) and/or 30 mM of adenosine. MEASUREMENTS AND MAIN RESULTS: Free cytosolic calcium concentration was determined by fluorescent spectroscopy, utilizing the calcium chelator, FURA-2AM. Sepsis was associated with a significant increase in erythrocyte intracellular calcium concentration as compared with nonseptic controls (96.26 vs. 45.38 nM; p < .001). Similar changes could be induced by endotoxin incubation of whole blood (84.52 vs. 40.45 nM; p < .001). This endotoxin-induced increase was independent of extracellular calcium concentration and was only partially ameliorated by calcium-channel blockade. Inhibition of intracellular calcium release was ineffective in altering the endotoxin-induced increase in the erythrocyte intracellular calcium value. In contrast, pretreatment with either adenosine or ATP minimized these increases. Posttreatment with ATP, but not adenosine, allowed partial reversal of this endotoxin-induced increase in intracellular calcium. CONCLUSIONS: Sepsis induces alterations of erythrocyte intracellular calcium homeostasis. A significant increase in free cytosolic concentrations of intracellular calcium is characteristic of this altered homeostasis. These changes are reproducible by the incubation of whole blood with endotoxin. This increase in cytosolic calcium concentration appears to be independent of extracellular calcium concentration, transmembrane calcium channels, and/or intracellular calcium stores. It can, however, be modulated through provision of high-energy phosphates and/or their precursors to the cell itself. PMID- 7874896 TI - Multiple organ failure after liver transplantation. AB - OBJECTIVE: To examine the effect of multiple organ failure after liver transplantation on mortality and resource utilization. DESIGN: Retrospective cohort study. SETTING: Surgical intensive care unit in a tertiary care university hospital. PATIENTS: Consecutive series of 113 adults undergoing liver transplantation between 1984 and 1992. Patients were excluded if they died intraoperatively (n = 2), required retransplantation (n = 8), or had incomplete records (n = 7). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We prospectively developed definitions for organ failure, and quantitated the frequency and related outcomes for mortality and resource utilization. Multiple organ failure was defined as the presence of two or more organ failures. Patients were grouped according to the presence (n = 31) or absence (n = 65) of multiple organ failure. Preoperative severity of illness was assessed by the Acute Physiology and Chronic Health Evaluation (APACHE II) and United Network for Organ Sharing (UNOS) scoring systems. Postoperative outcome data, including hospital survival rate, hospital length of stay, and charges were recorded. The frequency of multiple organ failure after liver transplantation was 32%. The mortality rate in the patients who developed multiple organ failure was 42% vs. only 2% in those patients without multiple organ failure (p < .0001). Patients with four or more organ failures had a 100% mortality rate. Postoperative multiple organ failure was associated with increased hospital length of stay (46 +/- 7 days vs. 29 +/- 2 days; p = .026) and increased hospital charges ($271,497 +/- 29,994 vs. $136,372 +/- 8,310; p < .0001). Higher preoperative APACHE II and UNOS scores predicted postoperative multiple organ failure, but were less accurate tools for predicting risk of death. CONCLUSIONS: Multiple organ failure is associated with death and increased resource utilization in liver transplantation. Pretransplantation severity of illness, as measured by APACHE II and UNOS scoring systems, is an important determinant of postoperative multiple organ failure and outcome. PMID- 7874897 TI - Inflammatory mediators in relation to the development of multiple organ failure in patients after severe blunt trauma. AB - OBJECTIVE: To evaluate the posttraumatic course of several inflammatory mediators or markers (complement components C3, C3a, terminal complement complex, thromboxane B2, C-reactive protein, elastase, and neopterin) in relation to the development of multiple organ failure and mortality. DESIGN: Prospective study of a selected patient group. SETTING: Surgical intensive care units in three European trauma hospitals. PATIENTS: Patients (n = 56) with severe blunt trauma (Injury Severity Score of > or = 33). INTERVENTIONS: Arterial blood samples were sequentially obtained. MEASUREMENTS AND MAIN RESULTS: Nonsurvivors (n = 8) had significantly higher circulating C3a and elastase concentrations on the first postinjury day, compared with survivors (n = 48). No differences between these groups were found for terminal complement complex, thromboxane B2, C-reactive protein, and the neopterin/creatinine ratio. Five patients died before day 5. Eighteen patients developed multiple organ failure, which was diagnosed from day 5 onward, leaving 33 patients without multiple organ failure. The patients with subsequent multiple organ failure showed significantly higher mean circulating concentrations of C3a (914 +/- 190 [SEM] ng/mL), terminal complement complex (57 +/- 17 U/mL), and thromboxane B2 (275 +/- 37 pg/mL) at the first postinjury day than the patients without multiple organ failure (566 +/- 110 ng/mL, 27 +/- 2 U/mL, and 169 +/- 14 pg/mL, respectively). In patients with multiple organ failure, elastase concentrations were significantly higher on days 2, 3, 4, and 5 postinjury. Neopterin/creatinine ratios, on the other hand, were significantly higher in patients with multiple organ failure when the multiple organ failure had already become established (on days 8 and 10). CONCLUSION: In multiple trauma patients, excessive triggering of the inflammatory cascade-as expressed by complement activation and stimulation of neutrophils producing elastase--plays an important and early role in the development of multiple organ failure. PMID- 7874898 TI - Gastric emptying in critically ill patients is accelerated by adding cisapride to a standard enteral feeding protocol: results of a prospective, randomized, controlled trial. AB - OBJECTIVE: To investigate the effect of cisapride, a relatively new prokinetic agent, on gastric emptying in critically ill patients. DESIGN: Prospective, randomized, controlled study. SETTING: Adult medical/surgical intensive care unit in a university hospital. PATIENTS: Twenty-one consecutively enrolled patients, requiring prolonged mechanical ventilation and enteral feeding. INTERVENTIONS: Patients were randomized to receive either no cisapride or 10 mg of cisapride four times daily, which was added to a standard enteral nutrition feeding protocol. MEASUREMENTS AND MAIN RESULTS: Gastric emptying was evaluated by daily measurements of gastric residue and on days 5 through 7 by bedside scintigraphy. Normal values for gastric clearance of a tracer-labeled test meal and for measurements obtained in the supine position were determined in ten healthy volunteers. The mean time at which 50% of the technetium 99m-labeled test meal was eliminated from the stomach (T 1/2) in this control group was 31 +/- 15 mins. In ten critically ill patients (enteral nutrition group), gastric emptying was markedly delayed after 5 to 7 days of enteral feeding (mean T 1/2 = 78 +/- 40 mins; p < .002 as compared with the control group). In contrast, patients treated with cisapride (cisapride group) showed an accelerated gastric emptying (mean T 1/2 = 18 +/- 7 mins; p > .05 as compared with controls; p < .005 as compared with enteral nutrition group). The mean gastric residue over a 1-wk period was also significantly lower in the cisapride group than in the enteral nutrition group (17.7 +/- 8.9 vs. 94.5 +/- 33.4 mL; p < .001). CONCLUSIONS: The data indicate that gastric emptying in critically ill, sedated, and mechanically ventilated patients can be significantly improved by adding cisapride to a routine enteral feeding protocol. PMID- 7874899 TI - Alteration in swallowing reflex after extubation in intensive care unit patients. AB - OBJECTIVES: To assess the swallowing reflex after prolonged endotracheal intubation and to assess the influence of age and duration of intubation on this reflex. DESIGN: Prospective, observational, clinical study. SETTING: The intensive care unit of a university teaching hospital. PATIENTS: The swallowing reflex was studied after extubation in 34 patients and compared with the deglutition in 30 nonintubated patients with a nasogastric tube and 15 nonintubated patients without a nasogastric tube. INTERVENTIONS: Four volumes of normal saline (0.25, 0.50, 0.75, and 1 mL) were injected at the epipharynx level. Swallowing efficiency was assessed by the latency between instillation and the first swallow, as identified on a submental electromyogram. The tests were performed immediately (day 0), and at 1 (day 1), 2 (day 2), and 7 (day 7) days after extubation in the intubated group. Nonintubated patients were tested once. MEASUREMENTS AND MAIN RESULTS: On day 0, the latency was increased for each bolus in the extubated group when compared with the control groups. Significant shortening of latency after 0.50, 0.75, and 1 mL injections of normal saline occurred on days 1 and 2 when compared with day 0, whereas no change was observed after 0.25 mL of normal saline was injected. On day 7, a significant improvement was observed, regardless of the volume injected. There was no correlation between swallowing latency and either the age of the patients or the duration of endotracheal intubation. CONCLUSIONS: These data indicate that prolonged endotracheal intubation impairs the swallowing reflex, with improvement within 1 wk. This phenomenon could contribute to microinhalations and aspiration pneumonia after extubation. PMID- 7874900 TI - Decreased splanchnic perfusion measured by duplex ultrasound in humans undergoing small volume hemorrhage. AB - OBJECTIVES: To quantitate duplex Doppler measurements of splanchnic perfusion to determine if these measurements are reproducible in euvolemic humans and if such measurements are sensitive to mild degrees of systemic hypovolemia. DESIGN: Prospective, nonrandomized, controlled trial. SETTING: Clinical research center. PARTICIPANTS: Seven fasting, healthy male and female volunteers, ranging in age from 25 to 37 yrs and weighing 60 to 90 kg. INTERVENTIONS: Pulse, blood pressure, hematocrit, and duplex Doppler measurements of the peak systolic velocity and time averaged velocity of the subdiaphragmatic aorta, celiac artery, and superior mesenteric artery were obtained at four time points. Time points I and II were on separate days before hemorrhage and consisted of routine blood donation of 450 mL. Time point III was immediately after blood donation. Time point IV was 24 hrs after donation. Estimated blood flow was calculated from time averaged velocity (estimated blood flow = 60[vessel cross-sectional area][time averaged velocity]). MEASUREMENTS AND MAIN RESULTS: Vital signs and hematocrit remained without significant change at all time points. Peak systolic velocity, time averaged velocity, and estimated blood flow were also unchanged between measurements at time points I and II. However, after a mean reduction of 9.1% of total blood volume, duplex ultrasound detected significant decreases of 14.5% in celiac artery and superior mesenteric artery peak systolic velocity, as well as 15.1%, 17.3%, and 20.2% decreases in aorta, celiac artery and superior mesenteric artery time averaged velocity and estimated blood flow, respectively (all values p < .05 vs. baseline, Duncan's multiple range test). All measured variables returned to baseline 24 hrs after hemorrhage. CONCLUSIONS: Noninvasive duplex Doppler measurements of splanchnic peak systolic velocity, time averaged velocity, and estimated blood flow are reproducible and sensitive to small changes in intravascular volume. These data suggest a potential clinical role for duplex imaging in the treatment of critically ill patients to guide therapy to optimize splanchnic perfusion. PMID- 7874901 TI - A technique revisited: hemodynamic comparison of closed- and open-chest cardiac massage during human cardiopulmonary resuscitation. AB - OBJECTIVE: To compare the hemodynamics of closed-chest cardiac massage vs. open chest cardiac massage in patients resuscitated from cardiac arrest that occurred outside of the hospital. DESIGN: Prospective, non-outcome, case series. SETTING: Large urban emergency department. PATIENTS: Ten adult, normothermic, nontraumatic, out-of-hospital, cardiac arrest patients who failed advanced cardiac life support (ACLS) therapy. INTERVENTIONS: Patients presenting to the hospital in cardiac arrest were managed according to the ACLS protocol at the clinician's discretion. Proximal aortic and central venous pressure catheters were placed to measure arteriovenous compression- and relaxation-phase pressure gradients. After 5 mins of baseline measurements during closed-chest cardiac massage, patients underwent a left lateral thoracotomy, and open-chest cardiac massage was performed for 5 mins. MEASUREMENTS AND MAIN RESULTS: The mean coronary perfusion pressure and compression-phase pressure gradients were 7.3 +/- 5.7 and 6.2 +/- 5.4 mm Hg, respectively, during closed-chest cardiac massage, while increasing to 32.6 +/- 17.8 and 32.6 +/- 29.9 mm Hg, respectively, during open-chest cardiac massage. The differences between both measurements were statistically significant (p < .05). CONCLUSIONS: Open-chest cardiac massage is superior to closed-chest cardiac massage in providing relaxation-phase and compression-phase pressure gradients during cardiac arrest in patients failing current ACLS protocols. During open-chest cardiac massage, all patients exceeded the minimum coronary perfusion pressure of 15 mm Hg, which is recommended to obtain a return of spontaneous circulation. Further outcome studies are needed to determine the timeliness and appropriate indications for open-chest cardiac massage. PMID- 7874902 TI - Medical effectiveness of esophageal balloon pressure manometry in weaning patients from mechanical ventilation. AB - OBJECTIVE: To determine the efficacy of a new respiratory monitor, which uses esophageal balloons, in aiding clinicians attempting to wean patients from mechanical ventilation. DESIGN: Prospective study of patients who were deemed ready to be weaned after having required mechanical ventilation for a minimum of 3 days. Each of the patients served as his or her own control. SETTING: University medical intensive care unit. PATIENTS: The series consisted of 23 consecutive patients who were ready to wean from mechanical ventilation. INTERVENTIONS: Before the onset of the study, two weaning strategies were developed. One strategy involved using clinically available weaning parameters. The other strategy involved using esophageal balloon data that was recorded via a new respiratory monitor. Each of the weaning strategies resulted in the development of a scoring system that could be rigidly adhered to and which determined, without bias, to what extent the patient could be weaned each day. Rigid criteria were also developed to determine whether the weaning trial was successful or not. The two strategies were then compared to determine the ability of the strategy to shorten ventilatory time. MEASUREMENTS AND MAIN RESULTS: Each patient was evaluated daily by the two weaning protocols. At each weaning step, the two protocols were compared with respect to degree of aggressiveness and tolerance of the weaning maneuver by the patient. A protocol was judged superior if it resulted in more aggressive weaning without increased patient intolerance. The clinicians evaluating the patient with the clinical protocol could accelerate or retard the number of weaning steps by one step, based on the patient's clinical state and the clinician's experience. There was no such freedom in the esophageal protocol. The major finding was that in 40.5% of the instances, the protocol involving the esophageal balloon resulted in more aggressive weaning without patient intolerance. In 11.6% of the cases, the clinical protocol was more aggressive. Both protocols predicted the same number of weaning steps 39.8% of the time. In all these instances, the patient tolerated the weaning suggested. The use of data from the esophageal protocol resulted in weaning the patients 1.68 days faster than the use of data from the clinical protocol. CONCLUSIONS: The respiratory monitor, using esophageal balloon technology, is effective in that it can provide the clinician with data that can result in more aggressive weaning from mechanical ventilation without an increase in patient intolerance. The duration of mechanical ventilation can be shortened when these data are applied via a rigidly controlled weaning strategy. PMID- 7874903 TI - Maternal and fetal colloid osmotic pressure following fluid expansion during cesarean section. AB - OBJECTIVES: To characterize the changes in colloid osmotic pressure during delivery and to determine the relationship between maternal and fetal colloid osmotic pressures. DESIGN: Clinical, prospective study. SETTING: Obstetrical operating theater in a tertiary care university hospital. PATIENTS: Thirty healthy parturient patients, at term gestation receiving spinal anesthesia for elective cesarean section. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Maternal colloid osmotic pressure samples were obtained at the time of intravenous insertion and delivery. Fetal umbilical vein and umbilical artery colloid osmotic pressure samples were measured from the umbilical cord at delivery. The volume of intravenous infusion and dose of ephedrine were recorded for each patient. Maternal colloid osmotic pressure at delivery was significantly less than that value measured at the time of intravenous catheter insertion in each patient (15.8 +/- 0.3 vs. 23.1 +/- 0.3 mm Hg; p < .0001). Umbilical artery colloid osmotic pressure was consistently higher than umbilical vein colloid osmotic pressure (21.0 +/- 0.4 vs. 19.4 +/- 0.3 mm Hg; p < .0001). Both umbilical artery colloid osmotic pressure and umbilical vein colloid osmotic pressure were significantly higher than maternal colloid osmotic pressure at delivery (p < .0001). The volume of intravenous infusion and the dose of ephedrine both correlated inversely with maternal colloid osmotic pressure measured at delivery (p < .05). CONCLUSIONS: The reduction in maternal colloid osmotic pressure during delivery is, in part, related to intravenous fluid expansion and the amount of vasopressor administered. Despite the significant fluctuations in maternal colloid osmotic pressure, the placenta and fetus possess the capability to alter colloid osmotic pressure. PMID- 7874904 TI - Sodium bicarbonate may improve outcome in dogs with brief or prolonged cardiac arrest. AB - OBJECTIVE: Despite the absence of outcome evaluation, the use of sodium bicarbonate in cardiac arrest has declined based on advanced cardiac life-support guidelines. The effects of bicarbonate therapy on outcome in a canine model of ventricular fibrillation cardiac arrest of brief (5-min) and prolonged (15-min) duration were examined. DESIGN: Prospective, randomized, controlled trial. SETTING: Experimental animal laboratory in a university medical center. SUBJECTS: Thirty-two adult dogs, weighing 10 to 17 kg. INTERVENTIONS: The animals were prepared with ketamine, nitrous oxide/oxygen, halothane, and pancuronium. Ventricular fibrillation was then electrically induced and maintained in arrest for 5 mins (n = 12) or 15 mins (n = 20). Canine advanced cardiac life-support protocols were instituted, including defibrillation, cardiopulmonary resuscitation (CPR), and the administration of epinephrine (0.1 mg/kg), atropine, and lidocaine. The bicarbonate group received 1 mmol/kg of sodium bicarbonate initially, and base deficit was corrected to -5 mmol/L with additional bicarbonate, whereas acidemia was untreated in the control group. Cardiopulmonary values were recorded at intervals between 5 mins and 24 hrs, and the neurologic deficit score was determined at 24 hrs after CPR. MEASUREMENTS AND MAIN RESULTS: The treatment group received an additional 2 to 3 mmol/kg of bicarbonate in the early postresuscitation phase. Compared with controls, the bicarbonate group demonstrated equivalent (with brief arrest) or improved (with prolonged arrest) return of spontaneous circulation and survival to 24 hrs, with lessened neurologic deficit. The acidosis of arrest was decreased in the prolonged arrest group without hypercarbia. Improved coronary and systemic perfusion pressures were noted in the bicarbonate group with prolonged arrest, and the epinephrine requirement for return of spontaneous circulation was decreased. CONCLUSIONS: The empirical administration of bicarbonate improves the survival rate and neurologic outcome in a canine model of cardiac arrest. PMID- 7874905 TI - In vivo effects of prostacyclin on segmental vascular resistances, on myogenic reactivity, and on capillary fluid exchange in cat skeletal muscle. AB - OBJECTIVE: To analyze the local circulatory effects of prostacyclin in skeletal muscle. DESIGN: A prospective experimental study. SETTING: A university laboratory. SUBJECTS: Twelve adult cats. INTERVENTIONS: The study was performed on autoperfused, sympathectomized gastrocnemius muscle. MEASUREMENTS AND MAIN RESULTS: Arterial blood flow, total and segmental vascular resistances (arterial vessels of > 25 microns, arterioles of < 25 microns, and veins), hydrostatic capillary pressure, tissue volume, myogenic reactivity, and the capillary filtration coefficient were followed. The capillary filtration coefficient reflects the functional capillary fluid exchange area. Myogenic reactivity was evaluated as the arteriolar resistance increase after a standardized decrease in extravascular pressure. Arterial infusion of prostacyclin decreased vascular resistance by approximately 50% at the highest dose given (500 ng/kg/min). This effect was more pronounced on the arterial side, especially in arterial vessels of > 25 microns. Hydrostatic capillary pressure increased by 1.9 +/- 0.3 mm Hg, causing fluid filtration. The relative fluid filtration was less than that value shown for some other vasodilator drugs (isoprenaline, calcium-channel blockers, thiopental) in this muscle preparation. Capillary filtration coefficient decreased by 25%. Myogenic reactivity was depressed but to a lesser extent than previously observed for other vasodilator mechanisms (muscle exercise, beta adrenergic receptor stimulation, thiopental infusion, nifedipine infusion). CONCLUSIONS: Prostacyclin is a vasodilator, both on the arterial and venous side, that restricts the increase in hydrostatic capillary pressure. The decrease in capillary filtration coefficient most likely reflects a decrease in capillary permeability, explaining the smaller relative filtration rate. The relatively well-preserved myogenic reactivity may imply a better preserved microvascular flow distribution and peripheral oxygen uptake. PMID- 7874906 TI - Acute, subacute, and chronic histologic effects of simulated aspiration of a 0.7% sucralfate suspension in rats. AB - OBJECTIVE: To assess the acute (4-hr), subacute (7-day), and chronic (21-day) effects of simulated aspiration of a 0.7% sucralfate suspension in rats. DESIGN: Prospective, multigroup trial in which rats were randomized to various simulated aspiration groups. SETTING: Experimental animal laboratory. SUBJECTS: Forty-five Sprague-Dawley rats. INTERVENTIONS: Simulated aspiration was induced by single, direct, tracheal instillation of 2 mL/kg of either room air, sucralfate, or normal saline. MEASUREMENTS AND MAIN RESULTS: Lung histologic changes were assessed using a quantitative numerical scoring scale. There was an increase in bronchiolar inflammation in rats undergoing acute, simulated sucralfate aspiration compared with controls. There were no significant differences (p > .05) in any other features at any time interval studied (two-way analysis of variance). CONCLUSIONS: Even though significant inflammatory airway lesions were produced in this acute model, these abnormalities resolved without evidence of subacute or chronic histologic progression. It remains to be determined if this pattern is unique to this specific experimental model or if it can be extrapolated to critically ill patients. PMID- 7874907 TI - Renovascular interaction of epinephrine, dopamine, and intraperitoneal sepsis. AB - OBJECTIVE: To determine the effect of intraperitoneal sepsis on the systemic and renal actions of the continous infusion of epinephrine or dopamine, and during the concurrent administration of both drugs. DESIGN: Prospective, randomized study. SETTING: Laboratory at a university hospital. SUBJECTS: Seven conscious, chronically catheterized, adult merino sheep. INTERVENTIONS: Epinephrine at 40 micrograms/min or dopamine at 2 micrograms/kg/min, or both drugs concurrently were infused for 4 hrs on separate study days in healthy sheep. This protocol was then repeated following the induction of sepsis after the intraperitoneal injection of 10(11) Escherichia coli, 10(12) Bacteroides fragilis, and bran. MEASUREMENTS AND MAIN RESULTS: Systemic oxygen delivery (DO2) and consumption were measured using thermodilution cardiac output and measured oxygen content. Renal blood flow was measured using an electromagnetic flow transducer, and creatinine clearance was calculated as the quotient of renal blood flow and the renal extraction ratio of creatinine. Infusion of epinephrine augmented systemic DO2 and mean arterial pressure (MAP) during both healthy and septic studies. Systemic oxygen consumption was only increased during epinephrine infusion in the septic study. During the healthy animal study, renal blood flow was initially decreased during epinephrine infusion, but increased to 36% above baseline (p = .003). However, creatinine clearance remained unchanged. During the experimental sepsis study, the infusion of epinephrine had less marked effects on renal blood flow (unchanged from baseline), while an initial reduction (15 mins) in creatinine clearance (p = .04) was not sustained and had returned to baseline by 3 hrs. Dopamine alone produced no change in systemic oxygen variables or MAP during the studies on healthy or septic animals. Although dopamine produced renal vasodilation and an increase in renal blood flow in the healthy state, these results were not found during the septic state. In addition, concurrent infusion of dopamine with epinephrine did not alter the systemic or renal effects of epinephrine during the healthy or septic states. CONCLUSIONS: These results do not support the routine use of low-dose dopamine, and demonstrate a change in renovascular responses to catecholamines during intraperitoneal sepsis. The infusion of epinephrine at 40 micrograms/min had few deleterious effects on the kidney, and augmented both MAP and systemic DO2. Its role as a catecholamine in the management of sepsis may need to be reconsidered. PMID- 7874908 TI - Effect of hemorrhagic shock and reperfusion on the respiratory quotient in swine. AB - OBJECTIVES: Respiratory quotient, the ratio of CO2 production to oxygen consumption (VO2), is principally affected by the fuel source used for aerobic metabolism. Since the respiratory quotient, VO2, and CO2 production cannot be directly measured easily, indirect calorimetry is commonly used to determine the value of these variables at the airway level (i.e., airway respiratory quotient, airway VO2, and airway CO2 production). However, under nonsteady-state conditions, a variety of phenomena can alter the relationship between true metabolic activity and measurements determined by indirect calorimetry. During exercise, for example, airway respiratory quotient increases as anaerobic threshold is reached because of the disproportionate increase in airway CO2 production that results from the CO2 liberated through the buffering of excess hydrogen ions by bicarbonate. We hypothesized that hemorrhage and reinfusion might change airway respiratory quotient in a consistent manner as shock is produced and reversed. DESIGN: Prospective laboratory study. SETTING: University animal laboratory. SUBJECTS: Eight pigs (25 +/- 2 [SD] kg), anesthetized with fentanyl and relaxed with pancuronium bromide, and mechanically ventilated on room air. INTERVENTIONS: The animals were sequentially hemorrhaged and then autotransfused while metabolic and hemodynamic measurements were obtained, using continuous indirect calorimetry and continuous applications of the Fick principle. Hemoglobin, arterial lactate concentration, and blood gases for calibration were measured serially. Analysis of variance was used to compare various periods in time. MEASUREMENTS AND MAIN RESULTS: Between baseline and peak hemorrhage, and between peak hemorrhage and postreinfusion, all of the following variables changed significantly (p < .05): airway VO2 (baseline 6.4 +/- 0.9 mL/min/kg, peak hemorrhage 3.9 +/- 0.6 mL/min/kg, postreinfusion 7.0 +/- 1.4 mL/min/kg); airway CO2 production (baseline 5.5 +/- 0.9 mL/min/kg, peak hemorrhage 4.5 +/- 0.9 mL/min/kg, postreinfusion 6.0 +/- 1.4 mL/min/kg); airway respiratory quotient (baseline 0.87 +/- 0.07, peak hemorrhage 1.16 +/- 0.07, postreinfusion 0.87 +/- 0.05); lactate concentration (baseline 2.4 +/- 1.2 mmol/L, peak hemorrhage 6.7 +/- 1.9 mmol/L, postreinfusion 5.1 +/- 2.0 mmol/L); and delta PCO2 (venous PCO2-PaCO2) (baseline 4.5 +/- 3.6 torr [0.6 +/- 0.5 kPa], peak hemorrhage 12.1 +/- 5.3 torr [1.6 +/- 0.7 kPa], postreinfusion 2.7 +/- 2.7 torr [0.4 +/- 0.4 kPa]). CONCLUSIONS: Airway respiratory quotient increases in hemorrhagic shock and decreases again as shock is reversed during reinfusion. This phenomenon appears related to the buffering of excess of hydrogen ion during hemorrhagic shock. PMID- 7874909 TI - Cardiorespiratory effects of perfluorocarbon-associated gas exchange at reduced oxygen concentrations. AB - OBJECTIVE: To determine whether reducing FIO2 during perfluorocarbon-associated gas exchange would cause deterioration of hemodynamics, lung mechanics, or gas exchange in normal piglets. DESIGN: A prospective, controlled animal trial. SETTING: Experimental animal laboratory in a university setting. SUBJECTS: Twelve normal, anesthetized piglets, 7 to 14 days old, and weighing 3.31 +/- 0.75 kg. INTERVENTIONS: After the induction of anesthesia, tracheostomy and catheterization, piglets were stabilized. They were mechanically ventilated with a tidal volume of 15 mL/kg, inspiratory time of 25%, positive end-expiratory pressure of 4 cm H2O, and a respiratory rate of 20 to 28 breaths/min to obtain a baseline PaCO2 between 34 and 45 torr (4.7 and 6.0 kPa). Each animal was studied during continuous positive-pressure breathing, and during perfluorocarbon associated gas exchange. They were ventilated at an FIO2 of 1.0 for 15 mins. FIO2 was randomly varied among 0.75, 0.5, and 0.3 every 15 mins, then returned to 1.0. At each FIO2, measurements of gas exchange, lung mechanics, and hemodynamics were made. After continuous positive-pressure breathing, perfluorocarbon-associated gas exchange was instituted by replacing the gaseous functional residual capacity of the lungs with perfluorooctylbromide. Animals were then ventilated and measurements were taken. MEASUREMENTS AND MAIN RESULTS: At each FIO2, measurements of gas exchange (arterial blood gases and saturation), lung mechanics (mean airway pressure, static end-inspiratory pressure, and peak inspiratory pressure), and hemodynamics (heart rate, and mean arterial, right atrial, pulmonary artery occlusion, and pulmonary arterial pressures) were recorded. In six piglets, cardiac output was measured at each FIO2 by thermodilution. Cardiac index, indexed oxygen delivery and consumption, and indexed pulmonary vascular resistance were derived using standard formulas. Piglets were well saturated at all FIO2 settings during continuous positive pressure breathing. However, during perfluorocarbon-associated gas exchange, arterial saturation decreased to 72% at an FIO2 of 0.3. Cardiac index and oxygen consumption were not affected by reducing FIO2 during perfluorocarbon-associated gas exchange, and were not significantly different than during continuous positive-pressure breathing. Oxygen delivery was reduced at an FIO2 of 0.3 during perfluorocarbon-associated gas exchange, but oxygen consumption remained in the flow independent portion of the curve despite arterial desaturation. Pulmonary arterial pressure was higher during perfluorocarbon-associated gas exchange than during continuous positive-pressure breathing. Pulmonary arterial pressure and indexed pulmonary vascular resistance were significantly higher during perfluorocarbon-associated gas exchange at an FIO2 of 0.3 than at any other FIO2 settings. CONCLUSIONS: Piglets showed no adverse effects on lung mechanics during perfluorocarbon-associated gas exchange. Hemodynamics were well supported at all FIO2 settings, and arterial blood was fully oxygenated during perfluorocarbon associated gas exchange at an FIO2 of > or = 0.5. PMID- 7874910 TI - Survey of critical care management of comatose, head-injured patients in the United States. AB - OBJECTIVE: This survey was designed to study current practices in the monitoring and treatment of patients with severe head injury in the United States. DATA SOURCES: The collected data represent answers to telephone interviews of nurse managers, clinical specialists, and staff nurses specializing in neurotrauma care at 277 randomly selected hospitals from a total pool of 624 trauma centers. Overall, 261 (94%) centers participated in the survey. Of the participating centers, 219 (84%) were providers of care for severely head-injured patients. In order to assess reliability and account for differences among respondents, personnel from 40 (15%) centers were resurveyed 6 months later and a different nursing professional was interviewed, although the questions remained the same. DATA EXTRACTION: The largest group of respondents came from level I centers (49%), followed by level II (32%) and level III (2%). Thirty-four percent of the surveyed hospitals had a designated neurologic/neurosurgical intensive care unit, and 24% of all units surveyed were under the direction of either a neurosurgeon or a neurologist. Twenty-eight percent of the centers routinely performed intracranial pressure monitoring, while 7% of the centers reported never using this technique. The use of ventriculostomy catheters for intracranial pressure monitoring was employed in 72% of the centers, but cerebrospinal fluid drainage was utilized by only 44% of the hospitals. The percentage of patients who had their intracranial pressure monitored was significantly higher in level I trauma centers and at hospitals that treated larger numbers of severely head-injured patients (15 to 30 patients per month, which represented 15% of the hospitals surveyed). Hyperventilation and osmotic diuretics were used in 83% of centers to reduce intracranial hypertension. The administration of barbiturates was reported in 33% of the units as a treatment for intracranial hypertension. Corticosteroids were used more than half of the time in 64% of trauma centers. Twenty-nine percent of the centers reported aiming for PaCO2 values of < 25 torr (< 3.3 kPa). CONCLUSIONS: The survey data indicate that there is a considerable variation in the management of patients with severe head injury in the United States. The establishment of guidelines for the management of head injury based on available scientific data and moderated by practical and financial considerations may lead to improvement in the standard of care. PMID- 7874911 TI - Pulmonary vascular resistance in infants after cardiac surgery: role of carbon dioxide and hydrogen ion. AB - OBJECTIVE: The objective of this study was to describe the effects of altering arterial PCO2 and pH on pulmonary vascular resistance in infants after cardiopulmonary bypass for cardiac surgery. DESIGN: Prospective study (with each patient as his or her own control). SETTING: Cardiac intensive care unit in a children's hospital. PATIENTS: We studied 15 infants (ages ranging from 0.4 to 15.6 months; median 5.7) who were mechanically ventilated during the immediate postoperative period after corrective cardiac surgery. INTERVENTIONS: The study was designed to have the following three stages: In the baseline stage, the initial postoperative hemodynamic parameters were stabilized and body temperature was normalized. In the hypercarbia stage, with FIO2 at 0.40, the rate of ventilation was decreased to produce an end-tidal CO2 level of > 55 torr (> 7.3 kPa). This stage established a clinical model of increased pulmonary vascular resistance. With the minute ventilation held constant in order to maintain a constant PaCO2, the arterial pH was increased by administration of a 4-mEq/kg iv dose of sodium bicarbonate (sodium bicarbonate stage). Arterial blood gas and hemodynamic determinations were obtained after a 10-min stabilization period at each stage. Drug infusions were not altered during the study period. MEASUREMENTS AND MAIN RESULTS: In the hypercarbia stage (stage 2), the mean PaCO2 increased from 36 +/- 5 torr (4.8 +/- 0.7 kPa) (at baseline) to 55 +/- 16 torr (7.3 +/- 2.1 kPa) (p < .01). As a result, the mean arterial pH decreased from 7.48 +/- 0.05 to 7.31 +/- 0.03 (p < .01). During this stage, the mean pulmonary arterial pressure increased from 21 +/- 6 to 30 +/- 8 mm Hg (p < .01) but the cardiac index remained unchanged (3.7 +/- 1.2 to 3.8 +/- 1.2 L/min/m2). Pulmonary vascular resistance index increased from 4.1 +/- 2.0 to 6.0 +/- 3.1 U.m2 (p < .01). After the administration of sodium bicarbonate (stage 3), the arterial pH increased to 7.44 +/- 0.06 (p < .05), while the PaCO2 was unchanged. The pulmonary vascular resistance index decreased to 3.1 +/- 1.5 U.m2 (from 6.0 +/- 3.1 U.m2; p < .01) as a result of both a decrease in mean pulmonary arterial pressure (to 26 +/- 6 mm Hg; p < .01) and a concomitant increase in cardiac index to 5.1 +/- 1.6 L/min/m2 (p < .01). CONCLUSIONS: Increasing the arterial pH by the administration of sodium bicarbonate both lowers the pulmonary arterial pressure and increases the cardiac index, resulting in a decrease in pulmonary vascular resistance. These changes were observed without alteration in PaCO2. Metabolic alkalosis may have a role in the treatment of increased pulmonary vascular resistance in infants after cardiopulmonary bypass for cardiac surgery. PMID- 7874912 TI - Teaching medical students complex cognitive skills in the intensive care unit. AB - OBJECTIVE: To determine if fourth-year medical students can learn the high-level cognitive skills needed to manage critically ill patients during a critical care medicine elective designed in accordance with established educational principles. DESIGN: Students were randomly assigned to take one of two examinations with ten short essay questions to complete on the initial day. After the elective, students completed the other examination in a crossover design. SETTING: Five surgical intensive care units (ICUs) in a tertiary care university teaching hospital. PARTICIPANTS: Fourth-year medical students enrolled in the critical care medicine elective. INTERVENTIONS: All students were enrolled in a critical care medicine elective consisting of an orientation, interactive conferences, technical skills laboratories, daily rounds, and patient-care experience. These components were designed to encourage problem-solving, improve analytical skills, and minimize the deterrents to education in the ICU. MEASUREMENTS: The primary outcome measure was the difference in examination scores before and after the rotation. Examinations were designed to test the student's skills in application, analysis, synthesis and evaluation. Specific questions concerning hemodynamic assessment were compared. MAIN RESULTS: The students' mean pre-elective scores were 58.8 +/- 10.8%, compared with 85.5 +/- 9.4% after the elective (p < .0001). CONCLUSION: Students can learn cognitive components of patient management skills using a format that encourages judgment, decision-making, and analytical skills, despite the liabilities inherent to education in an ICU. PMID- 7874913 TI - Guidelines for intensive care unit design. Guidelines/Practice Parameters Committee of the American College of Critical Care Medicine, Society of Critical Care Medicine. AB - OBJECTIVES: To develop guidelines that can serve as a reference for healthcare institutions wishing to design a new intensive care unit (ICU) or modify an existing ICU. DATA SOURCES: Medical, nursing, and architectural/design literatures from 1975 to the present related to ICU structure and function; current regulatory standards; consensus opinion of physicians, nurses, and architects with expertise in the ICU environment. DATA SYNTHESIS: Preference was given to regulatory standards and outcomes-based studies. If none was found, studies showing trends or preferences were combined with consensus opinion to derive models combining cost-efficiency and function. CONCLUSIONS: ICU design should reflect a multidisciplinary team approach by physician, nursing, administrative, and technical personnel. An optimum ICU design is described herein. Acceptable variations are indicated and essential aspects are emphasized. PMID- 7874914 TI - Left ventricular segmental wall motion abnormality in septic shock. PMID- 7874915 TI - Statistical analyses. PMID- 7874916 TI - Ketoconazole and nitric oxide. PMID- 7874917 TI - Selective digestive decontamination in critically ill patients. PMID- 7874918 TI - Management of severe anemia in a pediatric Jehovah's Witness patient. PMID- 7874919 TI - A different view of academic medicine. PMID- 7874920 TI - What we don't understand about ozone effects. PMID- 7874921 TI - Associating poor outcome with the presence of cytomegalovirus in bronchoalveolar lavage from HIV patients with Pneumocystis carinii pneumonia. PMID- 7874922 TI - Heliox for asthma. A trial balloon. PMID- 7874923 TI - The importance of rapidly treating patients with acute myocardial infarction. PMID- 7874924 TI - Significance of percutaneous needle biopsy in patients with multiple pulmonary nodules and a single known primary malignancy. AB - OBJECTIVE: To determine the necessity of percutaneous lung biopsy in patients with a single known primary malignancy and multiple pulmonary nodules. DESIGN: Retrospective study. SETTING: Tertiary care university hospital. RESULTS: We reviewed all percutaneous lung biopsy specimens over a 6-year period. One hundred forty-six patients with a single known primary malignancy and multiple pulmonary nodules had biopsies performed up to 19 years following diagnosis of the primary neoplasm. One hundred thirty-seven biopsy specimens (93.8%) were positive for metastases. Eight patients (5.5%) had a nondiagnostic biopsy specimen; however, subsequent imaging studies and the clinical course strongly suggested diffuse metastatic disease. One patient (< 1%) with breast carcinoma developed nodules 3 years after initial diagnosis and had resolution without a definitive diagnosis or therapy. CONCLUSION: Patients with a single known primary malignancy and multiple pulmonary nodules who present for percutaneous needle biopsy will have pulmonary metastases in the vast majority of cases. Biopsy in these patients rarely changes the clinical course as other diagnoses are rarely established. PMID- 7874925 TI - Linkage analysis of malignancy-associated sarcoidosis. AB - STUDY OBJECTIVE: To determine whether a reported association between sarcoidosis and malignancy can be supported. DESIGN: In this retrospective survey in a general community setting, we crossmatched the Kaiser Permanente Northwest Region (KPNW) Tumor Registry comprising 3 x 10(4) cases observed over 32 years against a sarcoidosis registry of 243 cases observed over 24 years. We used linkage criteria, eg, previously reported associated malignancies, late age onset of sarcoidosis, and close temporal proximity, to identify joint occurrences suggesting an etiologic relationship. We assessed the feasibility of detecting an association of sarcoidosis and Hodgkins disease (HD) by computing the required sample size based on incidence estimates of sarcoidosis and HD in this population. Medical records of 241 persons identified by the Tumor Registry as having HD were reviewed. SETTING: KPNW, a health maintenance organization. POPULATION: We studied 6.8 x 10(6) KPNW member-years from 1960 to 1992 at risk for malignancy; 5.6 x 10(6) member-years from 1971 to 1992 at risk for sarcoidosis. RESULTS: Six of the 11 (55%; 95% confidence interval, 26 to 84) correctly classified sarcoidosis and malignancy (S&M) cases met two or more linkage criteria. A seventh case, incorrectly classified as sarcoidosis, exhibited a necrotizing systemic granulomatous process, believed to represent a response to a fatal lymphoproliferative disorder. The mean age (40 years) of the 11 patients with S&M was 9 years higher than the mean age of the patients with sarcoidosis in the population from which they were drawn. The stage of sarcoidosis at diagnosis among the 11 S&M cases was exclusively 0 and I and thus divergent from expected values in this population. We found no instances of sarcoidosis accompanying HD. CONCLUSION: Linkage analysis provides evidence that S&M may be etiologically related in at least a quarter of cases in which both are present. PMID- 7874926 TI - Usefulness of morphometric evaluation of histopathologic slides in predicting long-term outcome of patients with squamous cell carcinoma of the lung. A preliminary report. AB - The present work was designed to evaluate the role of morphometric parameters in contributing to establish prognosis in 35 patients who underwent surgical resection of squamous cell carcinoma (SCC) of the lung. Morphometric studies were performed by means of point counting techniques. Patients considered as disease free survivors, ie, those without tumor recurrence for more than 60 months (n = 6), were designated as DOWELL, whereas the remaining 29 patients comprised the DOBAD group. In order to characterize DOWELL patients, multivariate models combining numeric and categoric variables were constructed considering numeric variables (age and morphometric parameters) or indexes for categoric data such as stage, and presence of residual tumor. Staging, incomplete tumor resection, and nucleus-cytoplasm ratio were selected by the model as significantly associated with survival. In addition, nuclear volume contributed (although nonsignificantly per se) to further refine the model by increasing its r value. Our results indicate that histopathologic data, when evaluated quantitatively, could predict prognosis in patients with SCC, together with staging and clinical data and encourage the use of morphometric procedures in the histopathologic analysis of SCC. PMID- 7874927 TI - Methacholine responsiveness is not associated with O3-induced decreases in FEV1. AB - STUDY OBJECTIVE: Controlled human exposure studies have suggested that the National Ambient Air Quality Standard for ozone (O3) may not provide a margin of safety to protect the most susceptible members of the population from adverse health effects. Although the subgroups of the population that are most susceptible to O3 have not been identified, recent work in our laboratory suggested that methacholine responsiveness might be an important determinant of susceptibility to O3. PATIENTS AND METHODS: To test the hypothesis that methacholine responsiveness is correlated with FEV1 response after O3 exposure, we conducted methacholine challenge tests and O3 (0.20 ppm) and filtered air exposures for 4 h with moderate exercise on 66 healthy individuals. RESULTS: Repeated measures analysis of variance demonstrated significant changes in FEV1 ( 0.82 +/- 0.63 L), FVC (-0.69 +/- 0.48 L), and specific airway resistance (SRaw) (+1.5 +/- 1.1 L x cm H2O/L/s) across the O3 exposure that persisted after adjusting for responses to air. Baseline PC100 (the concentration of methacholine that caused a doubling of the baseline SRaw) was weakly associated with O3 induced increases in SRaw (F1.54 = 2.85, p = 0.09), but not O3-induced declines in FEV1 or FVC. There was a weak association (r = -0.29) between O3-induced responses for SRaw and FEV1. The FEV1 responses for O3 were weakly associated with the symptoms of cough (r = -0.37), wheeze (r = -0.29), chest pain on deep inspiration (r = -0.31), and shortness of breath (r = -0.37), but not with chest discomfort or sputum production. CONCLUSIONS: Although we were unable to find support for our hypothesis, we found, somewhat surprisingly, that respiratory symptoms were weakly associated or unassociated with FEV1 responses after O3 exposure. This finding implies that individuals may experience adverse effects, ie, respiratory symptoms, without large declines in lung function. Conversely, individuals may suffer large declines in lung function without prominent symptoms and, therefore, may remain in an unhealthy environment despite evidence of toxicity. PMID- 7874928 TI - Dry powder inhalers are bioequivalent to metered-dose inhalers. A study using a new urinary albuterol (salbutamol) assay technique. AB - Metered-dose inhalers (MDIs) are extensively used to deliver drugs to the lungs but are driven by chlorofluorocarbon (CFC) propellants. The worldwide phasing out of CFCs within the next 5 to 10 years presents difficulties to the pharmaceutical industry. The mean +/- SD relative lung bioavailability of albuterol to the lung following inhalation of 400 micrograms of albuterol from an MDI, the Rotahaler and Diskhaler in 10 well-trained volunteers, was 2.83 (0.78), 1.72 (0.99), and 2.64 (1.23)%, respectively, expressed as a percentage of the nominal dose. The delivery of albuterol to the lungs from the MDI and Diskhaler was similar. In nine asthmatic subjects, the relative lung bioavailability of albuterol following inhalation with the MDI and Diskhaler was 1.19 (0.79) and 2.38 (1.46)%, respectively, expressed as a percentage of the nominal dose. There was no difference in reversibility 30 min after administration of the dose by the two methods. Similar lung deposition from the Diskhaler in volunteers probably is due to efficient MDI technique, which was absent in the asthmatic subjects. The Diskhaler does not rely on coordination during inhalation and therefore is easier to use. PMID- 7874929 TI - A workers' compensation claim population for occupational asthma. Comparison of subgroups. AB - STUDY OBJECTIVE: (1) To compare patients with claims submitted to the Ontario Workers' Compensation Board (WCB) for occupational asthma, in relation to the WCB decisions reached of occupational asthma (OA); aggravation of asthma from irritant exposures (AA); unrelated asthma; no asthma; and (2) to assess determinants of outcome of WCB accepted claims at permanent disability assessments. DESIGN: A retrospective review of 609 claims submitted to the WCB 1984 to 1988. RESULTS: The WCB decision reached was OA in 39% of claims, mostly attributed to isocyanates (57% of these). A further 39% were accepted for AA. Exposure to a known sensitizer occurred in 91% with OA and to an irritant in 67% with AA. Forty percent with AA were attributed to a spill or accidental exposure and 68% had preceding asthma. Those with AA were more likely to have clearing of symptoms by the time of their main assessment (43% vs 20% with OA) and were more likely to have remained in the same work (35% vs 20% with OA). Of 200 OA accepted claims reviewed at a mean of 1.9 years later, clearing of asthma occurred in 19% and milder asthma in 47%. Outcome was best with early diagnosis (p < 0.05), and milder impairment of pulmonary function at initial assessment (p < 0.05). CONCLUSIONS: Patients with asthma induced by a workplace sensitizer demonstrate some differences from those related to workplace irritants. Accurate categorization and early removal of those with OA offers the best prognosis. PMID- 7874930 TI - Slow-release theophylline in pregnant asthmatics. AB - STUDY OBJECTIVE: Oral theophylline treatment may be helpful in controlling severe asthma during pregnancy. This treatment, however, has been suspected of causing both complications and malformations. The objective of this investigation was to study the influence of theophylline treatment on the course of pregnancy and delivery and on maternal and infant health. SETTING: Respiratory unit, antenatal outpatient departments, and labor and delivery rooms. DESIGN: Case-control study. PATIENTS: The data of 212 pregnant asthmatics with theophylline treatment (AT) were compared with findings in 292 pregnant asthmatics without theophylline (A) and 237 nonasthmatic pregnant control subjects (C). RESULTS: There were no significant differences among groups as to age, height, age of onset of asthma, lung function, parity, or smoking. In the AT group, 19% were treated for acute exacerbations of the asthma as compared with 6% in the A group (p < 0.001). The incidence of preeclampsia was higher in the AT (15.6%) than in the C (6.4%) group (p < 0.03). Theophylline treatment at term was not associated with premature contractions or premature rupture of membranes, hemorrhage, placenta previa, abruption of the placenta, abnormal fetus position, frequent induction or augmentation of labor, prolonged third phase of delivery, or increased hemorrhage post partum. No differences among groups were seen with regard to gestational age, birth weight, Apgar scores, or perinatal deaths. Jaundice in the newborn, necessitating treatment with blue light, was more common in the AT (15.0%) than in the C group (7.8%) (p < 0.05). Three infants of 121 patients treated with theophylline during the first trimester were born with malformations; in the 91 patients treated with theophylline only during the second and third trimester, and the asthmatic control group, the corresponding figures were 4 and 3. CONCLUSIONS: During the second and third trimesters until term, theophylline treatment using moderate doses can be considered safe. The safety of theophylline treatment during the first trimester with regard to teratogenicity remains to be determined. PMID- 7874931 TI - Accuracy, reproducibility, and variability of portable peak flowmeters. AB - The accuracy, reproducibility, and variability of seven commercially available peak flowmeters were assessed using the pulmonary waveform generator as recommended by the American Thoracic Society. The standard models were tested for peak flows of 100, 200, 320, 500, and 700 L/min. The low-range models were tested for peak flows of 80, 150, 200, 250, and 320 L/min. Most of the units provided highly repeatable estimates of peak flow. However, the accuracy of several devices (Assess [Healthscan Products, Cedar Grove, NJ] and Mini-Wright [Clement Clarke International, Harlow, Essex, UK] low-range models, and the Ferraris [Ferraris Medical, Holland, NY] and Mini-Wright standard-range models) did not meet the National Asthma Education Program (NAEP) recommendations. The device with the best performance in terms of accuracy, variability, and reproducibility, and the only one in which all units tested met the NAEP recommendations, was the Astech (Center Laboratories, Port Washington, NY) full-range model. PMID- 7874932 TI - Peak inspiratory mouth pressure in healthy subjects and in patients with COPD. AB - The validity of peak inspiratory mouth pressure (P.PI-max) as a measure of inspiratory muscle strength was investigated by comparing it with sniff Pes in patients with COPD with respect to (1) learning effect, (2) reproducibility, and (3) measures of agreement. To assess the discriminating capacity of P.PImax, we compared the values in patients with COPD with those of healthy elderly subjects. Thirty-four patients (mean age, 62.5 years) with severe airways obstruction (FEV1, 44% predicted; FEV1/IVC, 37% predicted) and 149 healthy subjects (age > or = 55 years) were included. P.PImax was assessed during a maximal static inspiratory maneuver, while sniff Pes was assessed during a maximal sniff maneuver. Both maneuvers were performed from residual volume ten times on the same day. P.PImax showed no learning effect, while the sniff maneuver used seven attempts to obtain a maximal value. The intraindividual coefficients of variation of P.PImax and sniff Pes were 11.2% and 6.0%, respectively. Measures of agreement showed no significant discrepancies between the mean P.PImax and mean sniff Pes (0.29 kPa, p = 0.49). There was a significant correlation (r = 0.57, p < 0.001) between both measurements. P.PImax was significantly (p < 0.001) lower in both male (8.2 kPa) and female (6.2 kPa) patients with COPD compared with healthy men (11.0 kPa) and healthy women (8.8 kPa). We conclude that P.PImax is a valid and noninvasive assessment of inspiratory muscle strength. PMID- 7874933 TI - Ambulatory monitoring of peak expiratory flow. Reproducibility and quality control. AB - Eighty-five children and 230 adults from a population study performed ambulatory peak flow readings three times a day for 1 to 2 weeks following a home visit. Three peak expiratory flow (PEF) readings were reported for each of 5,809 test sessions. Within each test session, the third maneuver most frequently (40% of the time) gave the highest PEF reading. This did not vary throughout the day. In subgroups of children and women with a history of asthma or asthma symptoms (hereinafter referred to as "asthma"), the first maneuver during the evening test sessions more frequently gave the highest readings. However, maneuver-induced bronchospasm occurred during less than 5% of the test sessions in both subjects with asthma and in other subjects. The within test session PEF reproducibility was good: overall, the highest and second highest reading matched within one division (10 L/min) 73% of the time and within 30 L/min (9% of the reading) 95% of the time. The best reproducibility was noted after the first two days of testing, during evening and bedtime test sessions (vs morning), and in girls and men. In the group with at least 2 weeks of testing, the coefficient of repeatability (CR) for the week-to-week PEF lability index was 10% for healthy adults and 17% for healthy children. As expected, repeatability was not as good for adults with asthma (CR = 17%) and children with asthma (CR = 28%). PMID- 7874934 TI - Prospective assessment of cholesterol embolization in patients with acute myocardial infarction treated with thrombolytic vs conservative therapy. AB - PURPOSE: To determine whether subclinical cholesterol embolization is a frequent sequela of thrombolytic therapy. Case reports of catastrophic cholesterol embolization temporally associated with thrombolytic therapy in 19 patients have suggested a causal relationship. PATIENTS AND METHODS: We prospectively followed 60 patients with acute myocardial infarction who underwent coronary bypass surgery within 1 month. Twenty-nine received thrombolytic therapy for myocardial infarction; 31 were treated conservatively. Two muscle biopsy specimens and one skin biopsy specimen were obtained from the vein harvest site at the time of bypass surgery. Paraffin block and frozen sections from each biopsy specimen were analyzed for evidence of cholesterol embolization. RESULTS: Cholesterol emboli were found in biopsy specimens from 4 of 29 patients who had undergone thrombolytic therapy (14%) and in 3 of 31 patients who had not undergone thrombolytic therapy (10%, p = NS). Clinical evidence of cholesterol embolization occurred in one patient. Cholesterol emboli were distributed inhomogeneously; they were not observed in any skin biopsy specimen and were never present in more than one muscle biopsy specimen from each patient. CONCLUSIONS: The prevalence of cholesterol embolization in patients with acute myocardial infarction treated with thrombolytic therapy is not significantly higher than in those treated without thrombolytic therapy. The cholesterol embolization seen in 12% of our patients was mostly subclinical and was probably spontaneous and/or catheterization induced. Isolated case reports of severe cholesterol embolization temporally associated with thrombolytic therapy do not represent a phenomenon that has widespread subclinical occurrence. PMID- 7874935 TI - Surgical treatment of atrioventricular atresia combined with Wolff-Parkinson White syndrome. AB - BACKGROUND: Tachyarrhythmia has been thought to be an absolute contraindication for the Fontan operation. PATIENTS AND METHODS: Three patients, 22, 9, and 11 years of age, diagnosed as having atrioventricular atresia combined with the Wolff-Parkinson-White syndrome underwent surgical treatment. Each had drug resistant atrioventricular tachycardia that required direct cardioversion. Two patients with tricuspid atresia had an intermittent right-sided accessory pathway (ACP), and one with mitral atresia had a concealed left-sided ACP. The ACP was divided using an epicardial approach in two patients and an endocardial approach in one. Simultaneously, the Fontan operation was performed with atrioventricular connection (modified Fontan operation) in one patient, and a total cavopulmonary connection performed in another patient. In the remaining patient, ACP division was performed 3 years after the Fontan operation. RESULTS: There was no early death or other fatal complication, and the hemodynamic results were excellent. During the mean follow-up period of 68 months (range, 5 to 127 months), there has been no late death or recurrence of tachyarrhythmia. CONCLUSION: Tachyarrhythmias caused by ACPs are not contraindications for the Fontan operation. Concomitant surgery is advocated, as excellent short- and long-term results may be expected in these patients. PMID- 7874936 TI - Left atrial myxomas. Using gross anatomic tumor types to determine clinical features and coronary angiographic findings. AB - PURPOSE: To our knowledge, there have been no reports focusing on differences of clinical characteristics according to two gross anatomic types of cardiac myxomas. This study evaluated the differences of clinical features, coronary arteriographic findings, and histopathologic findings. PATIENTS AND METHODS: Twenty-six patients who underwent surgical excisions for left atrial myxomas were analyzed. According to the gross anatomic types, they were divided into two groups: group 1 having solid and ovoid myxomas (n = 14), and group 2 having soft and papillary myxomas (n = 12). Differences of presenting symptoms, prevalence of brain infarction, coronary angiographic findings, and histopathologic findings were analyzed. RESULTS: An incidence of dyspnea was significantly higher in group 1 (78.6% vs 33.3%, p < 0.05) than in group 2. That of neurologic symptoms was higher in group 2 (75% vs 14.3%, p < 0.01) than in group 1. A prevalence of brain infarction was higher in group 2 (75% vs 2.5%, p < 0.05) than in group 1. On coronary angiography, an identification rate of clusters of tortuous vessels was higher in group 1 (81.8% vs 0%, p < 0.01) than in group 2. In histologic findings, most of group 1 tumors displayed many hemorrhages, small vessels, and fibrosis in the stroma, but group 2 had few such structures. CONCLUSIONS: Coronary angiographic findings of tumor-feeding arteries without clusters of tortuous tumor vessels predict a myxoma that is papillary in type. At that time, close attention should be given for the possible existence of silent brain infarction. PMID- 7874937 TI - An echocardiographic evaluation of patients with idiopathic heart failure. AB - The primary myocardial disease idiopathic dilated cardiomyopathy (IDCM) is not clearly defined in the literature. The description is both morphologic and etiologic. We examined consecutive patients with congestive heart failure (CHF) of unknown cause to identify possible cases of IDCM and to give a detailed description of echocardiographic data and possible diastolic dysfunction in this group. The hospital records of patients aged 16 to 65 years hospitalized due to CHF or IDCM during a 6-year period (N = 2,711) were evaluated in a defined region of western Sweden. Twenty-two percent (584/2,711) of these records contained no plausible cause of CHF or IDCM, and among patients being alive, obvious cause was lacking in 411 of 1,516 (27%). These 411 patients were offered a diagnostic investigation, including echocardiography, and they were compared with a randomly selected control group (n = 103) from the general population. Of 411 patients, 293 accepted investigation. From the control group, we defined the reference level for left ventricular (LV) dilatation to be > 32 mm/m2, and reduced ejection fraction according to Teichholz formula to be < 50%. Applying these borderlines, we identified LV dilatation and systolic dysfunction to be present in 30%, either dilatation or systolic dysfunction in 36%, and neither in 34%. In patients without any signs of systolic dysfunction 44% (26/59) showed signs of diastolic dysfunction. In a multivariate analysis, LV dimension was not independently correlated to disease, although LV dimension was univariately correlated to ejection fraction (EF) (r = -0.59; p < 0.0001). However, EF (p < 0.0001), left atrial dimension (p < 0.0001), and the first third filling fraction (p < 0.0001) were the constellation of parameters that most accurately separated patients from controls. By using these three parameters, a positive and negative predictive accuracy of 98% and 61%, respectively, was achieved. Thus, in a consecutive group of patients with idiopathic CHF recruited from a nonselected group of hospitalized patients with CHF, all grades of ventricular function were found. In this group, 30% were identified as having IDCM. We give reference values for the diagnosis of idiopathic IDCM and a simple tool to identify patients with systolic and diastolic dysfunction. PMID- 7874938 TI - Left atrial appendage contractile function in atrial fibrillation. Influence of heart rate and cardioversion to sinus rhythm. AB - BACKGROUND: A high incidence of embolic phenomena is associated with atrial fibrillation (AF) and the left atrial appendage (LAA) is frequently the source of the emboli. Thrombus formation may be due to stasis within the fibrillating and inadequately emptying LAA. Because LAA emptying in AF may be the result of mechanical compression by the adjacent left ventricle, it is possible that left ventricular diastolic filling duration will importantly influence passive emptying of the LAA. We hypothesized that the magnitude of emptying of the LAA in AF is related to the duration of left ventricular diastolic filling which is determined by the ventricular response rate in AF. OBJECTIVE: The objective of our study was to determine the relationship of ventricular response rate in AF to LAA emptying and to assess the influence of sinus rhythm and heart rate on LAA emptying immediately after direct current cardioversion to sinus rhythm. METHODS: To study this, we used transesophageal echocardiography to measure LAA ejection fraction ([LAAmax-LAAmin]/LAAmax x 100%) and evaluated its relationship to left ventricular response rate (VRR) in 26 patients with AF (mean age, 65 +/- 7 [1 SD] years). RESULTS: There was a strong inverse relationship between LAA ejection fraction and VRR in AF (r = -0.73; p < 0.001). LAA ejection fraction during AF was 26 +/- 10%, and immediately after successful cardioversion, it increased to 46 +/- 12% (p < 0.001). However, during sinus rhythm there was no relationship between LAA ejection fraction and VRR (r = 0.06; p = NS) in the subgroup of patients who were successfully converted to sinus rhythm. There were poor relationships between LAA ejection fraction and peak transmitral flow velocity (r = -0.41; p = NS) or pulmonary venous flow velocity (r = -0.03; p = NS) in AF. CONCLUSION: These results indicate that the magnitude of LAA emptying in AF is strongly and inversely influenced by ventricular rate. Direct current cardioversion to sinus rhythm is associated with an increase in the magnitude of LAA emptying that is not influenced by heart rate. The magnitude of LAA emptying may be an important factor in the formation of thromboemboli in AF. The extent to which controlling the VRR in chronic AF will prevent stasis and LAA thrombus formation remains to be determined. PMID- 7874939 TI - Diaphragm levels as determinants of P axis in restrictive vs obstructive pulmonary disease. AB - BACKGROUND AND OBJECTIVE: Verticalized P axes in adults with obstructive lung disease have long been appreciated as characteristic of emphysema. After demonstrating P axes in restrictive lung disease to have a significantly different orientation (intermediate to horizontal), it was hypothesized that opposite effects on diaphragm level by obstructive disease (low diaphragm) and by restrictive disease (high diaphragm) could explain the axis differences, because the right atrium is attached via the inferior vena cava and adjacent pericardium to the right leaf of the diaphragm. METHODS: Electrocardiograms and chest radiographs were analyzed independently in a new series of 20 consecutive patients with purely obstructive and 19 consecutive patients with purely restrictive pulmonary disease. P axes were calculated to the nearest 5 degrees and grouped as vertical (+65 degrees to +90 degrees), intermediate (+40 degrees to +60 degrees), and horizontal (< +50 degrees). Chest radiographs established the right diaphragmatic level by posterior rib number or interspace with interspaces designated as "0.5" plus the number of the rib above. RESULTS: P axes for obstructive vs restrictive disease were different (p < 0.001) as in our previous investigation. In the present series, 19 of 20 electrocardiograms in patients with obstructive disease had vertical P axes between +70 degrees and +90 degrees; in 11 of 19 patients with restrictive disease, P axes were less than +40 degrees (horizontal); 6 were between +40 degrees and +60 degrees (intermediate); and only 2 were vertical. Diaphragm levels were between rib/interspace numbers 10.5 and 12.5 in all patients with obstructive disease. Diaphragm levels among patients with restrictive disease were higher and, like their P axes, more widely distributed: 10 of 19 between rib levels 8.0 and 9.5; only 4 at 10.5 or lower. Thus, vertical P axes corresponded to low (rib/interspace 10.5 to 12.5) and intermediate to horizontal P axes with higher (8.0 to 11.0 rib) diaphragm levels (p < 0.001). CONCLUSION: Because the separate P-axis distributions in restrictive and obstructive lung disease parallel the separate diaphragm levels and because the right atrium is necessarily carried by attachments to the right diaphragmatic leaf, it is likely that the consequent positional effects on the right atrium contribute to or cause the significantly different P-axis orientations in restrictive and obstructive pulmonary disease. PMID- 7874940 TI - Modulation of fibroblast activity in histiocytosis X by platelet-derived growth factor. AB - Platelet-derived growth factor (PDGF) was shown to modulate fibroblast activity in interstitial lung diseases like idiopathic pulmonary fibrosis (IPF). The role of PDGF in fibrosing mechanisms in histiocytosis X is unclear. Eight patients with histiocytosis X, five patients with idiopathic pulmonary fibrosis (IPF), and nine patients with no evidence of interstitial lung disease underwent bronchoalveolar lavage (BAL). The c-sis gene (a proto-oncogen encoding for the B chain of PDGF) expression was measured by gene hybridization revealing an upregulated c-sis transcript in the group of histiocytosis X and patients, whereas no c-sis expression was detectable in the control group. The alveolar macrophage supernatants from histiocytosis X patients and from the control group were incubated with a human lung fibroblast cell line (WI-38). The mitosis rate was measured by tritiated thymidine incorporation and collagen production was estimated by determining the procollagen III peptide concentration in fibroblast supernatants. Tritiated thymidine uptake was increased 1.6 times in histiocytosis X compared with the control group (p < 0.01). Procollagen-III-peptide levels in fibroblast supernatants after incubation with alveolar macrophage supernatants from histiocytosis X were elevated 2.5 times compared with the control group (p < 0.01). Prior to incubation with the WI-38 cell line, the cell supernatant then was preincubated with nonpreserved anti-human PDGF (AA- and BB-chain) resulting in an 80% decrease of tritiated thymidine uptake and procollagen-III-peptide production in the group of histiocytosis X patients compared with native supernatants. No significant change in fibroblast activity was seen in the control group. Preincubation with nonpreservated Ki-T2 antibodies as pan T lymphocyte marker did not show significant differences in both groups excluding unspecific antibody inhibition. These findings suggest increased PDGF production by alveolar macrophages in histiocytosis X patients. The PDGF is in part responsible for increased fibroblast replication and collagen production. PMID- 7874941 TI - Serum angiotensin-converting enzyme activity, concentration, and specific activity in granulomatous interstitial lung disease, tuberculosis, and COPD. AB - Angiotensin-converting enzyme (ACE) activity in serum is used as an aid to the diagnosis and follow-up of patients with sarcoidosis. A theoretical limitation of measurements of activity is that these may be affected by the presence of pharmacologic or endogenous inhibitors of ACE. Immunoassays of ACE concentration avoid this problem and, when combined with tests of ACE activity, permit calculation of specific activity of ACE. In this study, we set out to develop a sensitive radioimmunoassay for ACE to compare results obtained with this method with results of ACE activity and calculated ACE specific activity in patients suffering from a variety of lung diseases. In a group of control subjects (n = 32), the ACE concentration was 453.7 +/- 159.8 (SD) ng/mL; 95% confidence interval (CI), 398.34 to 509.06, but levels were significantly elevated in sarcoidosis (979.3 +/- 558.6 ng/mL; 95% CI, 827.5 to 1,131.1; n = 51; p < 0.001 vs control subjects), silicosis (646.5 +/- 239.1 ng/mL; 95% CI, 544.2 to 748.8; n = 21; p < 0.01), and miliary tuberculosis (647.0 +/- 217.1 ng/mL; 95% CI, 551.9 to 742.1; n = 29; p < 0.01). The levels were normal in COPD, interstitial pulmonary fibrosis, and active cavitary pulmonary tuberculosis. The overall correlation between ACE activity and concentration measurements was strong (r = 0.93). No evidence of endogenous ACE inhibition was observed in any of the disease categories studied except in COPD where an elevation of ACE specific activity was observed, raising the possibility that in this condition different isozymes of ACE with higher specific activity might be released. PMID- 7874942 TI - Hypersensitivity pneumonitis associated with home ultrasonic humidifiers. AB - We describe five patients with hypersensitivity pneumonitis (HP) that was related to using home ultrasonic humidifiers. All patients had micronodular infiltrates on their chest radiograph, and their lung biopsy specimens revealed alveolitis with or without epithelioid cell granulomas. Challenge tests were performed on two patients with the humidifier water and three patients using the humidifier. All patients tested exhibited a positive response. Tests for precipitating antibodies against an extract of the humidifier water gave strongly positive reactions in all patients tested. Precipitins to Cephalosporium acremonium and Candida albicans were also present in all cases, whereas precipitins to thermophilic actinomycetes were not detected. Although cultures of the water grew a variety of fungal and bacterial organisms, thermophilic actinomycetes could not be detected. These findings suggest that thermophilic organisms may not be the causative antigens of HP associated with ultrasonic humidifiers. All five patients had an increase in the bronchoalveolar lavage (BAL) lymphocytes that were predominantly CD4+ lymphocytes. The T helper cell count (CD4) to suppressor T cell count (CD8) ratio was significantly higher than that observed in summer type HP, and lower than that observed in bird fancier's lung, indicating that the phenotypes of the BAL lymphocytes may vary with the type of HP. PMID- 7874943 TI - The additive effect of theophylline on a high-dose combination of inhaled salbutamol and ipratropium bromide in stable COPD. AB - STUDY OBJECTIVE: To determine the additive effect of oral theophylline in patients with stable COPD who received both inhaled salbutamol, 400 micrograms, and ipratropium bromide, 80 micrograms, four times daily administered with a metered-dose inhaler. DESIGN: Twenty-four male patients with stable COPD (FEV1, 0.96 +/- 0.43 L; 36.8 +/- 17.0 percent predicted [% pred]) completed a randomized, double-blind, placebo-controlled crossover trial with oral theophylline for 4 weeks. MEASUREMENTS AND RESULTS: The average serum theophylline level was 15.0 +/- 5.5 micrograms/mL during treatment. On the whole, without inhalation of bronchodilators, FEV1 was 0.93 +/- 0.42 L during the placebo period and 1.00 +/- 0.43 L (significantly different from placebo; p < 0.01) during the theophylline period. At 15 and 60 min after inhalation of salbutamol, 400 micrograms, and ipratropium, 80 micrograms, the FEV1 with placebo was 1.12 +/- 0.43 L and 1.14 +/- 0.46 L, respectively, and the FEV1 with theophylline was 1.18 +/- 0.45 L (p < 0.01) and 1.20 +/- 0.47 L (p < 0.01), respectively. Daily peak expiratory flow rate also improved. Daily symptom scores were not significantly different between theophylline and placebo periods. Nevertheless, eight patients reported a subjective benefit during the theophylline administration period, and they were thus considered subjective responders. While FEV1 after inhalation was significantly improved during the theophylline periods in subjective responders (change in FEV1 between theophylline and placebo treatment 15 min after inhalation, 3.1 %pred; 60 min, 3.5 %pred), postbronchodilator FEV1 was not significantly different between the placebo and theophylline periods in subjective nonresponders (15 min, 1.7 %pred; 60 min, 1.6 %pred). CONCLUSIONS: On the whole, theophylline has a small bronchodilating effect but does not improve the symptoms of patients with stable COPD. However, one third of patients with COPD may respond subjectively to theophylline. The additive bronchodilating effect of theophylline may be related to the symptomatic improvement in subjective responders. PMID- 7874944 TI - Treatment of dyspnea in COPD. A controlled clinical trial of dyspnea management strategies. AB - We conducted a randomized clinical trial to evaluate a limited pulmonary rehabilitation program focused on coping strategies for shortness of breath but without exercise training. Eighty-nine patients with COPD were randomly assigned to either 6-week treatment or general health education control groups. Treatment consisted of instruction and practice in techniques of progressive muscle relaxation, breathing retraining, pacing, self-talk, and panic control. Tests of 6-min walk distance, quality of well-being, and psychological function as well as six dyspnea measures were administered at baseline, posttreatment, and 6 months after the intervention. Baseline pulmonary function tests also were obtained. At the end of the 6-week treatment, there were no significant differences between the treatment and control groups on any outcome measure. At the 6-month follow up, a significant group difference was seen on only one variable, Mahler's transition dyspnea index. The results of this evaluation suggest that a treatment program of dyspnea management strategies, without structured exercise training or other components of a comprehensive pulmonary rehabilitation program, is not sufficient to produce significant improvement in dyspnea, exercise tolerance, health-related quality of well-being, anxiety, or depression. PMID- 7874945 TI - Pulmonary rehabilitation improves exercise capacity in older elderly patients with COPD. AB - Pulmonary rehabilitation has been shown to improve exercise capacity in patients with COPD. It has been suggested that this improvement applies to all age groups; however, to our knowledge, the effects of pulmonary rehabilitation on older elderly patients (> or = 75 years of age) have not been studied. We compared changes in 12-min walking distance (12MD) and self-assessment scores in 47 older elderly patients with moderate to severe COPD who completed inpatient or outpatient pulmonary rehabilitation with those achieved by 87 younger patients who participated in the same programs from 1987 to 1992. There were 28 older elderly individuals (mean +/- SEM, 78 +/- 1 years) in the outpatient group and 56 younger patients (64 +/- 1 years). There were no differences between older and younger outpatients with respect to FEV1, FEV1/FVC, maximum inspiratory pressure (PImax), baseline 12MD, or baseline self-assessment score. After outpatient pulmonary rehabilitation, 12MD and self-assessment scores improved significantly in both groups. Inpatients included 19 older elderly individuals (81 +/- 1 years) who were also similar to the 31 younger inpatients (64 +/- 1 years) in FEV1, FEV1/FVC, PImax, and baseline self-assessment score, but they tended to be more limited in terms of baseline 12MD (p = 0.09). After inpatient pulmonary rehabilitation, significant improvements in 12MD and self-assessment were seen in both groups. We conclude that comprehensive outpatient and inpatient pulmonary rehabilitation programs are as beneficial in older elderly patients with COPD as they are in younger patients with similar lung function abnormalities. Patients 75 years of age or older should be considered for comprehensive pulmonary rehabilitation. PMID- 7874946 TI - The relationship between cytomegalovirus retrieved by bronchoalveolar lavage and mortality in patients with HIV. AB - STUDY OBJECTIVE: To evaluate mortality over 6 months of patients with HIV with cytomegalovirus (CMV) cultured from bronchoalveolar lavage (BAL) compared with those without CMV and to assess the significance of CMV cytologic study, CD4+ counts, and coexistent Pneumocystis carinii pneumonia. DESIGN: Retrospective evaluation of HIV-infected patients undergoing bronchoscopy with BAL. The 40 most recent HIV-positive patients undergoing bronchoscopy with BAL were included for each of three categories: CMV by cytologic study; CMV by culture only; and CMV absent. Patients for whom survival status at 6 months was unknown were excluded from analysis. SETTING: University hospital, tertiary care center. PATIENTS: Group 1 consisted of 36 patients with positive CMV culture and cytologic study and group 2 consisted of 38 patients with only a positive culture for CMV. Group 3 consisted of 40 patients with no evidence of CMV by BAL. RESULTS: On comparison of the groups, there was no difference in 3-week survival (from date of bronchoscopy). There was a statistically significant increase in mortality in group 1 patients compared with group 3 patients at both 3 and 6 months. Between groups 2 and 3, there was a difference in mortality that approached but did not reach significance at 3 months but did at 6 months. The mortality in group 1 at 3 months = 28%, at 6 months = 47%, whereas mortality in group 2 at 3 months = 26% and at 6 months = 45%. Group 3 had a 3-month mortality of 10% and a 6-month mortality of 15%. While those patients with positive CMV cytologic study had lower mean CD4+ counts, within the group, CD4+ counts were no different between the 3-month survivors and nonsurvivors (survivors, CD4/mm3 median = 38 [0 to 141]; and nonsurvivors, CD4/mm3 median = 16 [3 to 224]). Coinfection with P carinii did not increase mortality at 3 months. CONCLUSIONS: The CMV retrieved by BAL in HIV-infected patients was associated with significantly greater 3- and 6 month mortality. The CMV cytologic study did not predict a higher mortality and the difference in mortality between patients with and without CMV in BAL fluid was not directly attributed to lower CD4+ counts or P carinii coinfection. PMID- 7874947 TI - Effects of guaifenesin on nasal mucociliary clearance and ciliary beat frequency in healthy volunteers. AB - STUDY OBJECTIVE: Mucociliary clearance is an important host defense function of the upper respiratory tract that requires the coordinated beating of cilia and results in the transport of mucus to the oropharynx. Guaifenesin is a commonly prescribed drug that is reported to improve the clearance of respiratory secretions. We hypothesized that guaifenesin increases nasal mucociliary clearance related to increases in ciliary beat frequency (CBF) and that a direct relationship exists between nasal CBF and nasal mucociliary clearance. DESIGN: Double-blind placebo-controlled crossover study. PARTICIPANTS: Ten healthy volunteers with a previous history of sinus disease. INTERVENTIONS: Subjects received guaifenesin or placebo on days 1 to 7 or days 14 to 21. MEASUREMENTS AND RESULTS: In vivo saccharine transit time (STT) was measured by noting the time in minutes required for the subject to taste a saccharin particle placed on the inferior turbinate of the naris. The CBF was determined by video microscopy on ten separate groups of beating ciliated nasal mucosal cells obtained by brushing immediately after each STT determination. We found that there was no significant change between the guaifenesin-or placebo-treated groups from baseline values of STT (p = 0.94) or CBF (p = 0.46). Regression analysis demonstrated no relationship between STT and CBF for repeated measures within subjects (mean r2 = 0.18; mean p = 0.66) and between STT and CBF when all paired measurements were combined across subjects (r2 = 0.47; p = 0.46). CONCLUSION: We conclude that guaifenesin exerts no measurable effect on in vivo nasal mucociliary clearance or ex vivo nasal ciliary motility in healthy volunteers with previous sinus disease. In addition, there appears to be no relationship between nasal STT measured in vivo and CBF measured ex vivo. The lack of correlation is most likely due to variations in CBF related to sampling artifacts introduced by the nasal brushing process. PMID- 7874948 TI - Advance directives in the medical intensive care unit of a community teaching hospital. AB - STUDY OBJECTIVE: To evaluate the frequency with which advance directives (ADs) are available at the time of admission and their impact on subsequent care in a medical intensive care unit (MICU) setting before and 9 months after the implementation of the Patient Self-Determination Act (PSDA). DESIGN: Prospective nonrandomized cohort data collection and analysis. SETTING: Thirteen-bed MICU of community teaching hospital providing primary and referred care. PATIENTS: Consecutive admissions during 2-month periods separated by 1 year: August September 1991 (91) and August-September 1992 (92). MEASUREMENTS: The following were assessed: the presence and type or absence of AD at the time of admission; the presence or absence of a written order to limit resuscitation (WO-R) during the MICU stay; duration of MICU stay in hours; outcome; and combined duration of use or administration of seven selected interventions. MAIN RESULTS: Fifteen of 133 patients (11.3%) in the 91 group and 15 of 171 patients (8.8%) in the 92 group presented with an AD. This difference was not significant (p = 0.578). Most patients in both groups (75.9% in 91 and 80.1% in 92) presented without an AD and did not have a WO-R during their MICU course. In addition, most patients who did present with an AD, 11 of 15 (73.3%) in the 91 group and 14 of 15 (93.3%) in the 92 group, did not have a WO-R. A subgroup of older and more severely ill patients in both cohorts was identified; they did not present with an AD but subsequently a WO-R was established. These patients had the highest mortality, about 40%, when compared with the overall mortality of 8.2%. CONCLUSION: Advanced directives were infrequently available and had little impact on the pattern of care. PMID- 7874949 TI - Heliox therapy in acute severe asthma. AB - STUDY OBJECTIVE: To assess how patients with respiratory acidosis from acute severe asthma respond to helium-oxygen (heliox) mixtures. DESIGN: Consecutive case series. SETTING: Urban community teaching hospital. PATIENTS: Over a 2-year period, 12 asthmatics (mean age, 33.8 +/- 11.3 years) presented to the emergency department with acute respiratory acidosis (pH < 7.35 and PaCO2 > or = 45 mm Hg). All 12 patients were treated with heliox (60 to 70% helium/30 to 40% oxygen). Five patients received heliox through a ventilator and seven received heliox via face mask. RESULTS: Arterial blood gases (ABGs) were drawn immediately before and at a mean of 49.2 +/- 25.2 min after beginning heliox therapy. No therapeutic interventions were made between ABGs. For the entire group, the mean PaCO2 decreased from 57.9 to 47.5 mm Hg (p < 0.005) and the arterial pH increased from 7.23 to 7.32 (p < 0.001). In an attempt to find characteristics that might predict the response to heliox, a clinically significant response to heliox was defined as a drop in PaCO2 (to normal or by > or = 15%) coupled with a rise in pH by > or = 0.05. Using this definition, there were eight responders (67%) and four nonresponders (33%). The responders had a shorter duration of symptoms (17.8 vs 78.0 h, p < 0.05) and a lower preheliox pH (7.20 vs 7.30, p < 0.05). All of the responders presented within 24 h of symptom onset. Three of the four nonresponders reported prolonged (> or = 96 h) duration of symptoms, and two eventually required intubation. CONCLUSION: Heliox can rapidly improve ventilation in patients presenting to an emergency department with acute severe asthma with respiratory acidosis and a short duration of symptoms. PMID- 7874950 TI - Noninvasive pressure support ventilation in patients with acute respiratory failure. A randomized comparison with conventional therapy. AB - The benefit of noninvasive pressure support ventilation (NIPSV) in avoiding the need for endotracheal intubation and reducing morbidity and mortality associated with endotracheal intubation was evaluated in 41 patients who presented with acute respiratory failure not related to chronic obstructive pulmonary disease (COPD). Patients were randomly assigned to receive conventional therapy (n = 20) or conventional therapy plus NIPSV (n = 21). NIPSV was delivered to the patient by a face mask connected to a ventilator (Puritan-Bennett 7200a) set in inspiratory pressure support (IPS) mode. The mean levels of IPS, positive end expiratory pressure (PEEP), and fraction of inspired oxygen (FIO2) were respectively 15 +/- 3 cm H2O, 4 +/- 2 cm H2O, and 57 +/- 22%. The rate of endotracheal intubation (62 vs 70%, p = 0.88), the length of ICU stay (17 +/- 19 days vs 25 +/- 23 days, p = 0.16), and the mortality rate (33 vs 50%, p = 0.46) were not different between patients treated with NIPSV and those treated conventionally. Post hoc analysis suggested that in patients with PaCO2 > 45 mm Hg (n = 17), NIPSV was associated with a reduction in the rate of endotracheal intubation (36 vs 100%, p = 0.02), in the length of ICU stay (13 +/- 15 days vs 32 +/- 30 days, p = 0.04), and in the mortality rate (9 vs 66%, p = 0.06). We conclude that NIPSV is of no benefit when used systematically in all forms of acute respiratory failure not related to COPD. A subgroup of patients, characterized by acute ventilatory failure and hypercapnia, may potentially benefit from this therapy and further studies are needed to focus on this aspect. PMID- 7874951 TI - Multiplane transesophageal echocardiographic doppler imaging accurately determines cardiac output measurements in critically ill patients. AB - OBJECTIVES: To compare cardiac output and stroke volume measured by multiplane transesophageal Doppler echocardiography with that measured by the thermodilution technique. DESIGN: Prospective direct comparison of paired measurements by both techniques in each patient. SETTING: Cardiac surgery and myocardial infarction intensive care units. PATIENTS: Twenty-nine patients, mean age (+/- SD) 67 +/- 8 years. Nineteen had undergone open heart surgery and 10 had suffered acute myocardial infarction. METHODS: Cardiac output and stroke volume were measured simultaneously by the thermodilution technique and multiplane transesophageal Doppler echocardiography via the transgastric view (119 +/- 8 degrees) with the sample volume positioned at the level of the left ventricular outflow tract. RESULTS: Stroke volume and cardiac output measurements were obtained in 29 of 33 patients (88%). Mean values were 50 +/- 13 mL and 4.8 +/- 1.3 L/min by Doppler and 51 +/- 14 mL and 4.9 +/- 1.4 L/min by thermodilution (r = 0.90, r = 0.91, p < 0.001). The mean differences in values obtained with the two techniques were 1 +/ 6 mL (2 +/- 12%) and 0.1 +/- 0.7 L/min (2 +/- 12%). CONCLUSIONS: Multiplane transesophageal echocardiography enhances the ability to estimate accurately cardiac output and stroke volume by providing new access to left ventricular outflow tract in critically ill patients. PMID- 7874952 TI - Evaluation of transesophageal echocardiography as a diagnostic and therapeutic aid in a critical care setting. AB - OBJECTIVES: To assess the impact of transesophageal echocardiography (TEE) on therapeutic management in relation to pulmonary artery catheterization (PAC) in the ICU. DESIGN: Retrospective analysis of 108 consecutive TEE video and related patient files during a 7-month period. SETTING: A 33-bed medical and surgical ICU. METHODS: All critically ill patients with or without PAC in whom a TEE was performed, excluding postoperative cardiac surgical patients. Patients were divided in a cardiac and a septic group depending on the primary disease on admission to the ICU. The impact of TEE in relation to PAC on ICU management was evaluated in whether therapy changes were performed strictly on the basis of the TEE findings. MAIN RESULTS: Of 64% of patients with a PAC, 44% underwent therapy changes after TEE: 41% in the cardiac and 54% in the septic subgroup. In 41% of patients without a PAC, TEE led to a change in therapy. CONCLUSIONS: TEE results in altered therapeutic management in at least one third of our (noncardiac surgery) ICU patient population independent of the presence of a PAC. PMID- 7874953 TI - Effect of acute hypercapnia on alpha atrial natriuretic peptide, renin, angiotensin II, aldosterone, and vasopressin plasma levels in patients with COPD. AB - Disturbances in hormonal systems involved in sodium and water homeostasis are common during respiratory insufficiency. To investigate the role of hypercapnia, we designed a study to examine the hormonal response to acute hypercapnia induced at constant cardiac filling pressures and without hypoxemia. Seven sedated patients with COPD receiving mechanical ventilation were studied during five successive periods. Hemodynamics, arterial blood gases, and plasma hormone levels (atrial natriuretic peptide, renin, angiotensin II, aldosterone, vasopressin) were measured three times during 60 min of acute hypercapnia (52 +/- 5 mm Hg) and at control periods, before (36 +/- 4 mm Hg) and after (42 +/- 3 mm Hg) acute hypercapnia. During acute hypercapnia, mean pulmonary arterial pressure and cardiac output were increased without variation of other measured cardiorespiratory data and hormonal levels when compared with control values. After acute hypercapnia, cardiorespiratory variables returned to control values without variations of hormonal levels. Our results show that moderate acute hypercapnia does not significantly influence the hormonal levels when cardiac filling pressures and sympathetic tone remain stable. We suggest that changes in those plasma hormones involved in salt and water homeostasis during acute hypercapnia are secondary to hemodynamic changes induced by acute respiratory failure and not to acute hypercapnia per se. PMID- 7874955 TI - Dual effect of clonidine on isolated rabbit pulmonary arteries. AB - Clonidine, a partially selective agonist for alpha 2-adrenoceptors, has been increasingly used in anesthesia. Its direct effect on pulmonary arteries has not yet been clearly characterized. This in vitro study was performed to determine the vasoactive effects of clonidine on isolated rabbit pulmonary arteries. Responses of pulmonary artery rings from New Zealand white rabbits were assessed in the presence and absence of intact endothelium and with or without precontraction by norepinephrine (NE, 3 x 10(-6) M) or potassium chloride (KCl, 3 x 10(-2) M). Using tissue bath preparation, cumulative concentration response curves of clonidine were obtained at different concentrations (10(-8), 10(-7), 10(-6), 10(-5), 10(-4) M) after a period of stabilization. Clonidine caused vasoconstriction of isolated pulmonary arteries without any pretreatment. The magnitude of the constriction was dose related at lower concentrations and reached maximum of 300 g/g wet tissue when above 10(-6) M. On KCl-precontracted pulmonary arteries, clonidine caused significant dose-related vasoconstriction. On the NE-precontracted vessel rings, it elicited significant dose-dependent vasodilation up to 80% relaxation at 10(-4) M. All the above effects were endothelium independent. In conclusion, clonidine has dual endothelium independent vasoactive effects, causing vasoconstriction on isolated rabbit pulmonary arteries, either untreated or precontracted with KCl, and vasodilation on those precontracted with NE. Clonidine may act as a competitive alpha adrenoceptor blocking agent. PMID- 7874954 TI - Do plasma levels of circulating soluble adhesion molecules differ between surviving and nonsurviving critically ill patients? AB - Adhesion molecules appear to play a central role in tissue damage secondary to inflammatory response. Besides various neutrophil- and endothelial-bound adhesion molecules, soluble forms of endothelial-derived adhesion molecules have been detected in the circulating blood in recent years. They seem to be good markers of endothelial damage, but their importance in the critically ill has not been definitely elucidated yet. Plasma levels of circulating (soluble) adhesion molecules (endothelial leucocyte adhesion molecules [sELAM-1], vascular cell adhesion molecule 1 [sVCAM-1], intercellular adhesion molecule 1 [sICAM-1]) were serially measured from arterial blood samples using enzyme-linked immunosorbent assays (ELISA) in 50 consecutive patients suffering from severe trauma (injury severity score [ISS] > 25 points) or postoperative complications. Measurements were carried out on the day of admission on the intensive care unit (ICU) ("baseline" value) and during the next 5 days. Survival was defined as survival throughout the study period. The survivor group (n = 30) consisted of more patients who had sustained trauma (53%), whereas in the nonsurvivors (n = 20) more patients with postoperative complications were found (65%). On admission to ICU, septic shock was more often seen in the nonsurvivors (30%) than in the survivors (13%) and the nonsurvivors showed a slightly higher APACHE II score at baseline. At baseline, plasma levels of all three adhesion molecules were elevated beyond normal range in both groups. The sICAM-1 and sELAM-1 plasma concentrations were significantly higher in the nonsurvivors than in the survivors already at baseline. The sELAM-1 and sICAM-1 values significantly decreased in the survivors without reaching normal values. At the end of the investigation period, sVCAM-1 plasma level was within normal range in the survivors. In the nonsurvivors, all three adhesion molecules increased significantly throughout the study period (sELAM-1, from 115 +/- 31 to 158 +/- 23 ng/mL; sICAM-1, from 830 +/- 210 to 1,536 +/- 199 ng/mL; sVCAM-1, from 861 +/- 168 to 1,249 +/- 151 ng/mL). None of the other hemodynamic or laboratory variables could be correlated with the time course of adhesion molecules, except for PaO2/Pao2 ratio, which was negatively correlated with plasma levels of soluble adhesion molecules in the nonsurvivors (analysis of covariance). It is concluded that plasma levels of soluble adhesion molecules were markedly higher in nonsurviving than in surviving critically ill patients. They may possibly serve as markers of the extent of inflammatory response, of the endothelial damage in patients at risk of multiple-organ failure or both.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7874956 TI - Effects of diaphragmatic plication on respiratory mechanics in dogs with unilateral and bilateral phrenic nerve paralyses. AB - To examine the effects of diaphragmatic plication on respiratory mechanics during spontaneous breathing, we grouped 28 dogs into left phrenicotomy and plication (group L, n = 11), bilateral phrenicotomy and plication (group B, n = 9), and sham operations (group C, n = 8). In groups L and B, phrenicotomy caused significant (p < 0.05) decreases in tidal volume (VT), transdiaphragmatic pressure (delta Pdi), the ratio of gastric to esophageal pressure (delta Pga/delta Pes) and dynamic lung compliance (Cdyn), and significant (p < 0.05) increases in esophageal pressure (delta Pes), and the work of breathing (WOB) per liter of ventilation. In group L, plication resulted in significant (p < 0.05) increases in VT, delta Pdi, delta Pga/delta Pes, and Cdyn, and a significant reduction of WOB compared with phrenicotomy condition, indicating an improvement in the respiratory mechanics. However, in group B, no significant changes were observed after plication except for increased VT. In eight left-phrenicotomized open-chest dogs, transdiaphragmatic pressure (Pdi) and fractional shortening (FS) of right hemidiaphragm by right phrenic nerve stimulation increased significantly (p < 0.05) after plication, compared with the phrenicotomy condition, suggesting more effective kinetics of the right hemidiaphragm after plication of the left hemidiaphragm. Our results showed that diaphragmatic plication for unilateral paralysis is more effective than for bilateral paralysis, indicating that an improvement in kinetics of the intact hemidiaphragm plays an important role in functional recovery. PMID- 7874957 TI - Does airway pressure release ventilation alter lung function after acute lung injury? AB - BACKGROUND: During airway pressure release ventilation (APRV), tidal ventilation occurs between the increased lung volume established by the application of continuous positive airway pressure (CPAP) and the relaxation volume of the respiratory system. Concern has been expressed that release of CPAP may cause unstable alveoli to collapse and not reinflate when airway pressure is restored. OBJECTIVE: To compare pulmonary mechanics and oxygenation in animals with acute lung injury during CPAP with and without APRV. DESIGN: Experimental, subject controlled, randomized crossover investigation. SETTING: Anesthesiology research laboratory, University of South Florida College of Medicine Health Sciences Center. SUBJECTS: Ten pigs of either sex. INTERVENTIONS: Acute lung injury was induced with an intravenous infusion of oleic acid (72 micrograms/kg) followed by randomly alternated 60-min trials of CPAP with and without APRV. Continuous positive airway pressure was titrated to produce an arterial oxyhemoglobin saturation of at least 95% (FIO2 = 0.21). Airway pressure release ventilation was arbitrarily cycled to atmospheric pressure 10 times per minute with a release time titrated to coincide with attainment of respiratory system relaxation volume. MEASUREMENTS: Cardiac output, arterial and mixed venous pH, blood gas tensions, hemoglobin concentration and oxyhemoglobin saturation, central venous pressure, pulmonary and systemic artery pressures, pulmonary artery occlusion pressure, airway gas flow, airway pressure, and pleural pressure were measured. Tidal volume (VT), dynamic lung compliance, intrapulmonary venous admixture, pulmonary vascular resistance, systemic vascular resistance, oxygen delivery, oxygen consumption, and oxygen extraction ratio were calculated. MAIN RESULTS: Central venous infusion of oleic acid reduced PaO2 from 94 +/- 4 mm Hg to 52 +/- 9 mm Hg (mean +/- 1 SD) (p < 0.001) and dynamic lung compliance from 40 +/- 6 mL/cm H2O to 20 +/- 6 mL/cm H2O (p = 0.002) and increased venous admixture from 13 +/- 3% to 32 +/- 7% (p < 0.001) in ten swine weighing 33.3 +/- 4.1 kg while they were spontaneously breathing room air. After induction of lung injury, the swine received CPAP (14.7 +/- 3.3 cm H2O) with or without APRV at 10 breaths per minute with a release time of 1.1 +/- 0.2 s. Although mean transpulmonary pressure was significantly greater during CPAP (11.7 +/- 3.3 cm H2O) vs APRV (9.4 +/- 3.8 cm H2O) (p < 0.001), there were no differences in hemodynamic variables. PaCO2 was decreased and pHa was increased during APRV vs CPAP (p = 0.003 and p = 0.005). PaO2 declined from 83 +/- 4 mm Hg to 79 +/- 4 mm Hg (p = 0.004) during APRV, but arterial oxyhemoglobin saturation (96.6 +/- 1.4% vs 96.9 +/- 1.3%) did not. Intrapulmonary venous admixture (9 +/- 3% vs 11 +/- 5%) and oxygen delivery (469 +/- 67 mL/min vs 479 +/- 66 mL/min) were not altered. After treatment periods and removal of CPAP for 60 min, PaO2 and intrapulmonary venous admixture returned to baseline values. DISCUSSION: Intrapulmonary venous admixture, arterial oxyhemoglobin saturation, and oxygen delivery were maintained by APRV at levels induced by CPAP despite the presence of unstable alveoli. Decrease in PaO2 was caused by increase in pHa and decrease in PaCO2, not by deterioration of pulmonary function. We conclude that periodic decrease of airway pressure created by APRV does not cause significant deterioration in oxygenation or lung mechanics. PMID- 7874958 TI - Current status of thrombolysis in acute myocardial infarction. Part III. Optimalization of adjunctive therapy after thrombolytic therapy. PMID- 7874959 TI - Alternative pharmacotherapies for steroid-dependent asthma. PMID- 7874960 TI - Proto-oncogenes and the cardiovascular system. PMID- 7874961 TI - Futility and the common cold. How requests for antibiotics can illuminate care at the end of life. AB - The dominant approach to futility in medicine assumes that the probability and utility of medical interventions may be separated to provide a quantitative (probabilistic) definition of futility. This assumption is not only misleading but also responsible for much of the confusion that futility has engendered in medical discussions. The divorce of utility from probability is the opposite of how clinicians reason: an improbable intervention looks different if it is cheap, easy, and without morbidity than if it is technology intensive, expensive, and likely to involve great pain and suffering. Futility is how physicians describe the sense of being compelled to proceed with resource intensive care for marginal benefits. Outside the intensive care unit, physicians weigh and sometimes reject patient requests without the need to invoke futility. By examining the ways that physicians can legitimately evaluate patient requests, we can show that appeals to futility are both unnecessary and counterproductive. In cases where such appeals are unavoidable, the outpatient model suggests a process to adjudicate the competing claims of patient autonomy and physician responsibility. PMID- 7874962 TI - The impact of thoracoscopy on the management of pleural disease. AB - STUDY OBJECTIVE: To describe the diagnostic efficacy, morbidity, and patient outcome of thoracoscopy; to quantify the direct impact of thoracoscopy on clinical management; and to determine preoperative variables associated with finding malignancy at thoracoscopy to aid patient selection. DESIGN: Retrospective chart review of consecutive cases of thoracoscopy for pleural disease. SETTING: Single tertiary medical center. PATIENTS: One hundred eighty two consecutive patients who underwent thoracoscopy for pleural disease over a 5 year period (from 1987 through 1992). MEASUREMENTS AND RESULTS: Final diagnoses were 98 (54%) malignant, 58 (32%) benign, and 26 (14%) idiopathic. Thoracoscopy had a diagnostic sensitivity of 95% for malignancy and 100% for benign disease. Malignancy was shown by thoracoscopy in 27 of 41 (66%) patients who had a preoperative nondiagnostic closed pleural biopsy, and in 24 of 35 (69%) patients who had at least 2 preoperative negative pleural cytologic specimens. Chart review by preestablished criteria showed information obtained from thoracoscopy directly influenced treatment in 155 (85%) patients. Thirty-seven (20%) patients, however, had at least one perioperative complication (15% major, 8% minor). Ten (6%) patients died during the same hospitalization in which a thoracoscopy was performed, although none died within 48 h. There was one thoracoscopy-related death. Sixty-two (34%) patients died within 6 months of thoracoscopy (death by all causes). Forty-seven (48%) patients who had intrathoracic malignancy present at thoracoscopy died within 6 months. Patients found to have malignant pleural disease by thoracoscopy were more likely to have a preoperative history of a malignancy (p = 0.001). Age more than 50 years was associated with finding malignancy at thoracoscopy (p = 0.04). A combined lymphocytic and hemorrhagic effusion was associated with malignancy (p = 0.004). Preoperative pleural data showed that idiopathic effusions had a significantly lower median lactate dehydrogenase (LDH) value (192, which was normal) compared with malignant or benign effusions. CONCLUSIONS: (1) Thoracoscopy increases yield for malignant and benign disease when thoracentesis and closed pleural biopsy are nondiagnostic. (2) Thoracoscopy directly affects clinical management in 85% of patients. (3) Significant complications can occur in patients receiving tertiary care. (4) For the evaluation of suspected malignant pleural disease, thoracoscopy has its greatest diagnostic yield in older patients who have a history of malignancy and who present with a lymphocytic, hemorrhagic, high LDH effusion. PMID- 7874963 TI - Thoracoscopic-assisted lobectomy. Preliminary experience and results. AB - A preliminary report is made on the use of videothoracoscopy to achieve pulmonary lobectomy in 16 patients, including 12 with centrally located pulmonary metastases and 4 with benign lesions (3 bronchiectases and 1 endobronchial hamartoma). Videothoracoscopy was performed on eight right-lower lobes, one middle lobe, two right-upper lobes, four left-lower lobes, and one left-upper lobe with a thoracoscope and conventional thoracic instruments. All patients received standard pulmonary lobe resection with lymph node clearance similar to that achieved with open thoracotomy. The mean operative time was 3 h (range, 2.5 to 4 h). Average blood loss was 100 mL and mean length of hospital stay was 6 days (range, 4 to 8 days). A combination of videothoracoscopy with use of conventional instruments resulted in similar performance but less chest wall interruption than in conventional pulmonary lobectomy. Videothoracoscopy showed safer and faster lung resection, which subsequently minimized the perioperative morbidity. Pain intensity was lessened, functional recovery was quicker, and hospital stays were shorter in the patients we reviewed. PMID- 7874964 TI - The detection of collapsible airways contributing to airflow limitation. AB - The detection of collapsible airways, which may be a component of asthma and emphysema, has important therapeutic implications. We describe a patient with significant airways collapse contributing to his airflow limitation and discuss how collapsible airways can be assessed by the volume difference between what exits the lung as determined by a spirometer and the volume compressed as measured by the plethysmograph. More simply, a large volume difference between the slow and forced vital capacity (SVC-FVC), easily obtained from spirometry, may be used as a surrogate index of airway collapse. PMID- 7874965 TI - Recurrent pneumothorax and adenopathy. PMID- 7874966 TI - Acute dyspnea, chest tightness, and anemia in a 33-year-old man. PMID- 7874967 TI - Rapidly progressing dyspnea associated with a mass in the right side of the heart. PMID- 7874968 TI - Immunocytochemical detection of progesterone receptors. A study in a patient with primary pulmonary hypertension. AB - Primary pulmonary plexogenic arteriopathy (PPPA) is one of the principal conditions in which pulmonary hypertension may be clinically unexpected. It occurs in the lung vessels in the absence of any demonstrable cause. Its high incidence in women of childbearing age combined with reports of disease following delivery of a child or assumption of oral contraceptives suggest that hormonal factors may play a role in the pathogenesis of PPPA. The suspicion that the pulmonary vascular lesions occurring in PPPA could represent the effect of a hormonal mediated vascular hyperreactivity prompted the evaluation of the steroid hormone receptor status on lung tissue obtained from a women suffering from this disease who had a double-lung transplantation. By the immunocytochemical method performed on formalin fixed, paraffin-embedded lung tissue, we showed the presence of progesterone receptors (PR) in the nuclei of the myofibroblasts forming the arterial obstructive intimal proliferations and of the spindle cells present in the walls of the plexiform lesions. To enhance the staining and to facilitate the observation, we used a microwave-based antigen unmasking technique. The lack of estrogen receptors and the presence of PR could have increased, in the case, the sensitivity of the pulmonary muscular arteries to vasoconstrictory compounds. We hypothesize that on this substrate of a presumptive steroid-mediated vasoconstriction the sequence of the histologic lesions characteristic of pulmonary vascular hypertensive disease could have developed. PMID- 7874970 TI - Self-injection with olive oil. A cause of lipoid pneumonia. AB - A 48-year-old man with unipolar depression and a psychosexual problem concerning his body image was injecting his scrotum repeatedly with olive oil to increase the size of his genitals. He developed respiratory failure following accidental intravenous injection of olive oil and was found to have lipogranulomatous lesions in the lung and the scrotum. PMID- 7874969 TI - Diaphragmatic flutter presenting as inspiratory stridor. AB - Diaphragmatic flutter is a rarely reported disorder in which the diaphragm involuntarily contracts at a rapid rate. We report a unique case in which diaphragmatic flutter was associated with inspiratory stridor and was severely disabling. A new approach to the treatment of this condition, phrenic nerve crush, provided an optimal outcome, with resolution of symptoms and the return of normal diaphragmatic function. Pathophysiology and treatment of this condition are discussed. PMID- 7874971 TI - Lung herniation. A cause of chronic chest pain following thoracotomy. AB - Chronic chest pain is a common complication following thoracotomy, which is generally attributed to intercostal neuritis or neuralgia. Response to medical treatment is poor. We report a case of persistent chest pain following open lung biopsy, which was found to result from lung herniation, a rare, but surgically correctable complication of thoracotomy. Since lung herniation may be easily overlooked, this disorder should be considered more often in the differential diagnosis of persistent postthoracotomy chest pain. PMID- 7874972 TI - Acute sarcoid myositis with respiratory muscle involvement. Case report and review of the literature. AB - A 61-year-old woman with a history of sarcoidosis presented with acute sarcoid myositis affecting the respiratory muscles. The patient responded to prednisone therapy with improved pulmonary function test results and resolution of her symptoms. Acute myositis is a rare manifestation of sarcoidosis and should be treated with steroids. PMID- 7874973 TI - Allergic bronchopulmonary aspergillosis treated with itraconazole. PMID- 7874974 TI - The stomach is not a source for infection in ICU patients? PMID- 7874975 TI - Another viewpoint. What is a primary care physician? PMID- 7874976 TI - Amiodarone and the development of ARDS after lung surgery. PMID- 7874977 TI - Amiodarone and the development of ARDS after lung surgery. PMID- 7874978 TI - Incidence of endobronchial Kaposi's sarcoma. PMID- 7874979 TI - Digital localization of peripheral lung nodules with video-assisted thoracic surgery. PMID- 7874980 TI - Platypnea related to constrictive pericarditis. PMID- 7874981 TI - Unplanned extubation. PMID- 7874982 TI - Diagnosing central pulmonary artery thromboembolism. PMID- 7874983 TI - Resistive loading and pulmonary capillary volume in asthma. PMID- 7874984 TI - Bronchial vascular engorgement and airflow obstruction. PMID- 7874985 TI - Airway wall liquid. Sources and role as an amplifier of bronchoconstriction. AB - Airway liquid balance in asthma is largely determined by active plasma exudation from tracheobronchial microvessels into the interstitial spaces of the mucosa, submucosa, and/or adventitia, and from there into the luminal space. This exuded plasma is rich in proteins and cell mediators capable of initiating several events, including activation of sensory neural pathways, plasma protein cleavage, inflammatory cell recruitment, and inhibition of surfactant function. It can act to amplify the bronchoconstrictor response by increasing mucosal and/or submucosal thickness, altering mechanical properties of airway wall compartments, decoupling the airway wall from parenchymal attachments, filling airway interstices, and by creating an additional inward force because of surface tension, resulting in further airway constriction and possibly closure and thereby significantly increasing airways resistance. PMID- 7874986 TI - Theoretic effects of mucus gland discharge on airway resistance in asthma. PMID- 7874987 TI - Is asthma a fibrotic disease? PMID- 7874989 TI - Is asthma a nervous disease? The Parker B. Francis Lectureship. PMID- 7874988 TI - Major basic protein regulation of lung fibroblast cytokine production. Role of cytokine synergy and charge. PMID- 7874990 TI - Nitric oxide. Role as a relaxant agonist and transmitter of nonadrenergic noncholinergic inhibitory nerves in guinea pig trachea. PMID- 7874991 TI - Catalytic autoantibodies to vasoactive intestinal peptide. PMID- 7874992 TI - Is asthma an epithelial disease? PMID- 7874993 TI - Expression of interleukin-6 by airway epithelial cells. Effects on airway inflammation and hyperreactivity in transgenic mice. PMID- 7874994 TI - Asthma-associated viruses specifically induce lung stromal cells to produce interleukin-11, a mediator of airways hyperreactivity. PMID- 7874995 TI - The effect of treatment with corticosteroids on asthma airway structure and function. PMID- 7874996 TI - Interleukins impair beta-adrenergic receptor adenylate cyclase (beta AR-AC) system function in human airway epithelial cells. PMID- 7874997 TI - Anti-inflammation: direct physical association and functional antagonism between transcription factor NF-KB and the glucocorticoid receptor. PMID- 7874998 TI - Parenchymal mechanics and asthma. AB - The essence of asthma is impairment of expiratory flow. Expiratory flow requires lung recoil forces to supply the driving pressure and to tether the airways open. Lung recoil forces arise within the parenchymal structures, particularly the air liquid interface and elastin. Lung recoil is mainly elastic, but shows dissipative properties and contractility, and may be changed by volume history, time dependency, and plasticity. Lung recoil tethers the airway with peribronchial forces approximating pleural pressure but the peribronchial pressure departs systematically from this when the airway constricts, ie, "interdependence." In asthma, lung recoil may decrease due to changes in surfactant, stretching of connective tissues, and growth. Parenchymal-airway coupling may be changed by local changes in parenchymal properties and particularly by swelling of the adventitia due to edema, inflammation, or matrix remodeling. Such changes in lung recoil and airway coupling may explain some of the reductions of expiratory flow seen in asthma. PMID- 7874999 TI - Heterogeneity of airways obstruction in asthmatic patients using high-resolution computed tomography. PMID- 7875000 TI - New method for real-time measurements of changes in lumenal area of microsection explants of airways by videomicrometry. PMID- 7875001 TI - Relationships among airway-parenchymal interactions, lung responsiveness, and inflammation in asthma. Giles F. Filley Lecture. PMID- 7875002 TI - Peripheral lung mechanics may account for the rise in the maximal:partial ratio which follows hyperpnea-induced bronchospasm. PMID- 7875003 TI - Airway hyperresponsiveness in asthma. Is it unique? PMID- 7875004 TI - Increased sensitivity to the consequences of rhinoviral infection in atopic subjects. PMID- 7875005 TI - Nocturnal asthma. Structure and function. PMID- 7875006 TI - Properties of T lymphocytes from the airways of patients with asthma. Cytokine production and modulation by histamine. PMID- 7875007 TI - Evaluation of airway inflammation by endobronchial and transbronchial biopsy in nocturnal and nonnocturnal asthma. PMID- 7875008 TI - The Thomas L. Petty 37th Aspen Lung Conference: Asthma--Structure and Function. Proceedings. PMID- 7875009 TI - Theoretical basis of airway instability. Roger S. Mitchell Lecture. PMID- 7875010 TI - Mucosal folding and airway smooth muscle shortening. PMID- 7875011 TI - Structural and functional abnormalities of the airways of hyperoxia-exposed immature rats. PMID- 7875012 TI - Chronic allergic inflammation induces replication of airway smooth muscle cells in vivo in guinea pigs. PMID- 7875013 TI - Repeated allergen inhalations induce DNA synthesis in airway smooth muscle and epithelial cells in vivo. PMID- 7875014 TI - Tryptase-induced mitogenesis in airway smooth muscle cells. Potency, mechanisms, and interactions with other mast cell mediators. PMID- 7875015 TI - Is asthma a vascular disorder? PMID- 7875016 TI - Collagen shields delivery of netilmicin: a study of ocular pharmacokinetics. AB - Collagen shields have been used as therapeutic contact lenses to promote corneal epithelial healing and to deliver hydrosoluble drugs. In albino rabbits, we studied the ocular pharmacokinetics of netilmicin, an aminoglycoside antibiotic, released by a 24-hour collagen shield immersed for 10 min in commercially available eye solution of netilmicin, at the standard concentration of 3 mg/ml. The animals were sacrificed after 0.5, 1, 6 and 18 h. The antibiotic concentrations were measured by the microbiological method. The drug levels remained above the MIC for the usual pathogens for 18 h in the cornea and for 6 h in the aqueous humor. In the iris and ciliary body the peak concentration was reached 1 h after shield application, netilmicin concentration decreased thereafter rapidly. The lens and the vitreous did not appear to be permeated by the drug. In the conjunctiva, drug concentrations were low, showing a negligible lateral diffusion of netilmicin released by shields. In conclusion, our findings show, that if the collagen shields are used as delivery systems, a very concentrated drug solution is not required to obtain high and persistent levels of netilmicin in cornea. PMID- 7875017 TI - In vitro activity of isepamicin (Sch 21420), a new aminoglycoside. AB - The narrow therapeutic/toxic ratio of existing aminoglycosides has led to a search for safer drugs of this class. Isepamicin is a semi-synthetic aminoglycoside with a significantly low nephro as well as ototoxicity in animals and which is expected to have a clinical efficacy comparable to that of amikacin. We therefore compared its antibacterial activity with amikacin against 817 recent clinical isolates of gram-positive and gram-negative bacteria. The in vitro activity of isepamicin was comparable or slightly greater than amikacin against Staphylococcus aureus and most Enterobacteriaceae. However, it was significantly more inhibitory towards Serratia marcescens, Enterobacter and Klebsiella pneumoniae. PMID- 7875018 TI - Antibiotic susceptibility tests with fastidious and nonfastidious bacterial reference strains: effects of aerobic versus hypercapnic incubation. AB - Representative antimicrobial drugs were examined under aerobic and hypercapnic (3 and 5% v/v CO2) incubation with the Bauer-Kirby agar disk diffusion, a broth microdilution method, and the agar dilution procedure against nonfastidious, standard ATCC quality control strains and against two beta-hemolytic streptococcal, two pneumococcal, and three Haemophilus influenzae ATCC strains. It was found that an atmosphere of 3-5% CO2 merely antagonized amikacin, gentamicin, and netilmicin; the activity of penicillin G was antagonized only against Staphylococcus aureus ATCC 29213 in broth media, but not against any of the other strains. The activity of teicoplanin, and less so that of vancomycin, was enhanced only against S. aureus strain ATCC 25923, but not against the other strains. It was concluded that susceptibility tests, excluding aminoglycoside antibiotics, of beta-hemolytic streptococci, pneumococci, and H. influenzae and H. parainfluenzae should be incubated under 3% (candle jar or incubator) or 5% CO2 (incubator) so as to ensure optimal growth of capnephilic strains and thus avoid potentially misleading large inhibition zones of deceptively low minimal inhibitory concentrations. PMID- 7875019 TI - Canadian ofloxacin susceptibility study: a comparative study from 18 medical centers. Canadian Ofloxacin Study Group. AB - Ofloxacin, a newer fluorinated 4-quinolone having a broad spectrum of activity was evaluated against 5,553 clinical pathogens isolated from urine, respiratory tract, skin and genital tract infections at 18 Canadian Medical Centers spread across the nation. Approximately 300 strains were reported (zone diameters) from each site. The zones of ofloxacin, other fluoroquinolones, oral cephalosporins and penicillins were analyzed and interpreted by NCCLS criteria. Ofloxacin had the widest spectrum of activity against gram-positive organisms and most gram negative organisms, while ciprofloxacin was only superior for the Pseudomonas spp. The percentage of isolates susceptible to ofloxacin was as follows: for respiratory tract pathogens = 94%, for skin and soft tissue infections = 94%, for urinary tract organisms = 93% and for genital tract isolates = 94%. PMID- 7875020 TI - Candida glabrata, Candida krusei, non-albicans Candida spp., and other fungal organisms in a sixty-bed national cancer center in 1989-1993: no association with the use of fluconazole. AB - During the 5-year period 1989-1993, the incidence of Candida krusei, and other non-albicans Candida spp., was analyzed in a 60-bed cancer department. The frequency of C. krusei, before fluconazole was introduced into therapeutic protocols in 1990, was 16.5%, and after introduction of fluconazole into prophylaxis in acute leukemia in 1991, the incidence of C. krusei was 12.7%. After 3 years of using this drug in therapy and prophylaxis, the incidence of C. krusei in 1993 was 14.8%, what was lower than before this drug was introduced in our country. 97.6% of all isolated fungi were yeasts and only 2.4% were molds. Among yeasts, the most frequently isolated pathogen was Candida albicans with 64.3% in 1989 and 74.2% in 1993. The next was C. krusei with 21.2% in 1992 and 16.5% in 1989, but 14.8% in 1993, and Candida tropicalis and Candida glabrata with 9.03% in 1989 and 2.7% in 1993. Among the molds, Aspergillus spp. was the most frequently isolated genus. Analyzing the etiology of mycologically proven fungal infections confirmed by positive blood cultures or biopsies, C. albicans and Aspergillus spp. were the most common causative organisms. PMID- 7875022 TI - In vitro and in vivo activity of DQ-2556, a new cephalosporin. AB - The antibacterial activity of DQ-2556, a new cephalosporin, was compared with that of cefepime, cefpirome, and other antibiotics. DQ-2556 was more active than cefepime and less active than cefpirome against gram-positive bacteria. DQ-2556 was the most active compound against most members of the Enterobacteriaceae, such as Escherichia coli, Klebsiella, Proteus, Salmonella spp., and Shigella spp., and Haemophilus influenzae and Neisseria gonorrhoeae. In vivo, treatment with DQ-2556 was as or more efficacious than that with reference compounds in both systemic and respiratory tract infections in mice. DQ-2556 achieved higher concentrations than cefepime and cefpirome in lungs and kidney of mice. PMID- 7875021 TI - Enhancement of the susceptibility of Staphylococcus aureus to phagocytosis after treatment with fosfomycin compared with other antimicrobial agents. AB - Phagocytosis and intracellular killing of invading pathogens by host cells play the major role in resistance to bacterial infections. In vitro, antibiotics improve the susceptibility of microorganisms to antimicrobial activity of leukocytes, suggesting that this effect may contribute to determine the antimicrobial therapy and safe dosing intervals. The susceptibility of Staphylococcus aureus to phagocytosis and killing by human polymorphonuclear leukocytes (PMNL) in the presence of normal human serum in the postantibiotic phase of fosfomycin were compared with ciprofloxacin, cefotaxime and pristinamycin. Pretreatment of S. aureus for 10 min with 4 x MIC of fosfomycin and ciprofloxacin clearly sensitized the bacteria to leukocytic killing in the presence of normal human serum (10% v/v); cefotaxime and pristnamycin failed to enhance the phagocytic killing. PMID- 7875023 TI - Influence of subinhibitory concentrations of brodimoprim and trimethoprim on the adhesiveness, hydrophobicity, hemagglutination and motility of Escherichia coli. AB - In the present study the ability of subinhibitory concentrations (sub-MICs) of brodimoprim (a new 2,4-dimethoxybenzylpyrimidine) to interfere with some important aspects of bacterial cell function, such as surface hydrophobicity, fimbriation, motility and adhesiveness to mucosal cells, was investigated in comparison with those of trimethoprim. The inhibitory behavior of both diaminopyrimidines concerning hydrophobicity and hemagglutination (fimbriation) were essentially the same, while for adhesiveness and motility brodimoprim was more effective than trimethoprim. Diaminopyrimidines have high affinity for the bacterial enzyme dihydrofolate reductase, and this reduces the synthesis of essential purines and as a consequence of DNA and proteins. Our findings indicate that the synthesis and/or the expression of surface adhesins, which are proteins, was also affected by both brodimoprim and trimethoprim, the former being more active. PMID- 7875024 TI - Antitumor effect of erythromycin in mice. AB - Oral administration of erythromycin in the dose range of 1-10 mg/kg increased the survival times of tumor-bearing mice in both allogeneic and syngeneic mouse systems by two- to three-fold as compared with those of vehicle control mice, with the maximum effect at a dose of 5 mg/kg/day. During the early phase of tumor transplantation, tumoricidal macrophages and natural killer cells were active in the antitumor resistance of erythromycin-treated mice. Thereafter, the tumoricidal activity of macrophages became stronger as serum levels of interleukin-4 (IL-4) rose. Furthermore, treatment of mice with anti-IL-4 monoclonal antibody abolished the antitumor resistance conferred by erythromycin. These results indicate that erythromycin exhibits an indirect antineoplastic activity by enhancing the production of IL-4 which augments the tumoricidal activity of macrophages. PMID- 7875025 TI - Comparison of different schedules of ondansetron (GR 38032F) administration during cisplatin-based chemotherapy: a randomized trial. AB - The purpose of our study was to evaluate different schedules of ondansetron administration in cisplatin-induced emesis. All patients had previously received 2 cycles of CDDP-based chemotherapy in a dose of 100 mg/m2. Ondansetron was given by two schedules. Group A (45 patients) received a dose of 1 ampoule of 8 mg in 100 ml normal saline in a 10-min intravenous infusion before the infusion of CDDP; this was continued by 1 tablet of 8 mg in the afternoon and 1 before sleeping on the first day. For the next 3 days, the patients received 3 tablets of 8 mg daily. In group B (45 patients) the same doses were used at the same time and by the same route as in group A, except on the first day when all the dosages were intravenous. Nausea persisted for a longer time (A = 177 +/- 271 min, B = 78 +/- 83 min, p < 0.022), and it was intenser in group A (grade 0, p < 0.036, grade 1, p < 0.050) in comparison with group B. More patients of group B achieved complete (p < 0.015) and minor (p < 0.050) control of emesis, on the other hand group A presented an increased number with major (p < 0.015) and failure (p < 0.069) of control of emesis. There was no difference in nausea and vomiting for the next 3 days nor any difference in secondary side effects. We conclude that the intravenous administration schedule has shown superior antiemetic efficacy in patients who received cisplatin during the first 24 h. PMID- 7875026 TI - Angiotensin AII AT1 receptor mediates ethanol-diazepam inhibition of hippocampal LTP. AB - Within a limited range of doses, co-administration of ethanol (EtOH) and diazepam (DZ) produce enhanced anxiolytic effects. These combined effects on long-term potentiation (LTP) in the hippocampus of rats anesthetized with urethane were studied in an attempt to provide an explanation at a more fundamental neuronal level. Male Sprague-Dawley rats received 0.1, 0.5, 0.75 and 1.0 mg/kg DZ i.p. in combination with 0.1, 0.5, 0.75 g and 1.0 g/kg EtOH by gavage, respectively. Drugs were administered 20 min (EtOH) and 15 min (DZ) prior to tetanic stimulation of the medial perforant path which resulted in LTP induction measured in terms of the relative change in amplitude of the population EPSP as compared to baseline. Effects of both drugs alone and in combination on LTP are presented. Both drugs depressed LTP induction and significant enhanced interactive effects were observed. We have previously shown that angiotensin II (AII) inhibits LTP induction and that the inhibition can be blocked by losartan, an AII AT1 receptor antagonist. Our present results demonstrate that the combined inhibitory effects of EtOH and DZ on LTP induction are also blocked by losartan. PMID- 7875027 TI - Sympathoadrenal reactions during asphyxia in hypoglycemia and hyperglycemia of cats. AB - In 26 cats anesthetized with alpha-chloralose and urethane, cardiovascular changes during asphyxia in hypoglycemia and hyperglycemia were studied. Systemic hypoglycemia (serum glucose decrease from 148 to 31 mg/100 ml) was produced by i.v. injection of insulin 20 U/kg, followed by continuous I.V. infusion of 10 U/kg/hr. Systemic hyperglycemia (serum glucose increase from 187 to 657 mg/100 ml) was produced by I.V. infusion of 25% glucose at a rate of 1.5 gm/kg/hr. During hypo- or hyperglycemia, resting mean systemic arterial pressure (MSAP) and heart rate did not change significantly. Brain transection at various levels, i.e., midcollicular decerebration, ponto-medullary or medulla-spinal transection progressively decreased the resting MSAP, but not the heart rate. The most apparent reduction was at the medulla-spinal junction. After induction of systemic hypo- or hyperglycemia, plasma catecholamine concentrations increased significantly. Further increase occurred during asphyxia. Increases of MSAP and plasma catecholamine concentrations during asphyxia were attenuated after midcollicular decerebration and decreased further after subsequent ponto medullary and medulla-spinal transections. Increases in plasma catecholamines during asphyxia were greater in hypoglycemic than those in hyperglycemic state. The increase in plasma catecholamine persisted in hypoglycemic animals during asphyxia after midcollicular decerebration and ponto-medullary transections. As the terminal stage of asphyxia approached spasmodic contractions of urinary bladder occurred. Bladder contractions were abolished after intracerebroventricular (lateral) injection of insulin (0.25 unit/kg). In conclusion, asphyxia produced very marked cardiovascular and plasma catecholamine responses during hypo- or hyperglycemia and more so during the former condition. These reactions depend mainly on the neural mechanisms of medullary structures. Neural structures rostral to the midcollicular level are not essential. PMID- 7875028 TI - Actions of isoproterenol on amygdalar neurons in vitro. AB - The effects of isoproterenol (Iso) on neuronal excitability and synaptic transmission were investigated in slices of rat amygdala using intracellular recording technique. Most basolateral amygdala (BLA) neurons fired rapid action potentials which slowed or accommodated in response to a long-duration depolarizing current pulse. The end of depolarizing pulse was followed by an after-hyperpolarization (AHP). Superfusion of Iso (15 microM) reversibly blocked both the AHP and accommodation resulting in more action potential firing. Forskolin, a direct activator of adenylyl cyclase, mimicked the effect of Iso suggesting the involvement of cyclic adenosine-3',5'-monophosphate (c-AMP). Iso also produced a long-lasting enhancement of excitatory postsynaptic potential (EPSP). Pretreatment of the slices with propranolol completely prevented the effect of Iso confirming the mediation by beta-adrenergic receptors. These results suggest that the combined blockade of AHP and persistent potentiation of EPSP together form the cellular basis for the memory-enhancing effect of Iso in the amygdala. PMID- 7875029 TI - Effects of DL-tetrahydropalmatine on motor activity and the brain monoamine concentration in rats. AB - Behavioral and biochemical methods were used in this study to investigate the effect of DL-THP on motor activity and the concentration of monoamines in rats. Experimental results indicated that DL-THP significantly decreased the motor activity of rats and showed a dose-response pattern; in addition, it produced rigidity at a higher dosage. DL-THP also enhanced the hypomotility induced by haloperidol, but reduced the hypermotility produced by apomorphine. Furthermore, DL-THP significantly decreased the concentration of norepinephrine (NE), dopamine (DA) in the cortex and brain stem at lower and higher dosages, and the concentration of serotonin (5-HT) in the cortex at higher dosages. DL-THP also increased the concentration of homovanillic acid (HVA) in the cortex and brain stem at lower and higher dosages, and the concentration of 5-hydroxyindole acetic acid (5-HIAA) in the cortex at higher dosages. These results suggest that the hypomotility produced by DL-THP may be due to the increase in the turnover rate of dopamine in the cortex and brain stem at lower and higher dosages, and of serotonin in the cortex at higher dosages. PMID- 7875030 TI - The pressor effect of nicotine in the rostral ventrolateral medulla of rats. AB - It has generally been assumed that nicotine acts in autonomic ganglia to raise blood pressure. We considered that the pressor effect of nicotine might also involve central mechanisms. We tested this hypothesis in male Sprague-Dawley rats, Wistar-Kyoto (WKY) rats, and spontaneously hypertensive rats (SHR). The animals were anesthetized with urethane and blood pressure was monitored intraarterially. Nicotine was microinjected into various sites in the medulla using stereotaxic technique. While nicotine elicited bradycardia and hypotension in the nucleus tractus solitarii and area postrema, its injection into the rostral ventrolateral medulla (RVLM) produced a does-related and long-lasting increase in both systolic and diastolic pressure. This pressor effect of nicotine was not influenced by muscarinic receptor blockade (atropine 2.9 mumol intravenously), but was completely abolished by local nicotinic receptor blockade (hexamethonium 2.7 nmol). The WKY rats responded to nicotine administration into the RVLM with approximately equivalent changes in systolic and diastolic blood pressure and heart rate. The SHR was more sensitive to nicotine than WKY rats in producing pressor effect when it was injected into the RVLM. Thus, the increase of blood pressure consequent to nicotine is acting through nicotinic receptors in RVLM. These findings suggest a role for medullary nicotinic receptors in neural cardiovascular control and reveal an enhanced sensitivity to this effect of nicotine in the spontaneously hypertensive rat. PMID- 7875031 TI - Induction of perforated synapses in rat barrel cortex by whisker plucking. AB - To investigate synaptic alteration in the somatosensory cortex related to peripheral sensory blocking, the present study examined synapse number and structure within a single barrel following plucking of the C3 whisker of rat pups. The results indicate that whisker plucking produces no changes in synapse number and size, but does induce an early appearance of perforated synapses at P30 and P60, within the plucked whisker corresponding barrel. Thus, earlier occurrence of perforated synapses may indicate a representation of sensory experience. PMID- 7875032 TI - Urea transport in frog oocytes: effect of osmotic stress and vasopressin. AB - The transport of water and urea across biological membranes are considered to traverse separate channels or pores. While vasopressin responsiveness correlates with increased urea/water permeability in some epithelia, oocytes provide a single cell system to determine the coupling relationship. Urea transport under isotonic and hypotonic conditions are determined in full-grown frog oocytes in follicles. We found that urea reached equilibrium distribution (ratio of 14C-urea concentrations inside and outside of the oocyte) rapidly and remained equilibrated over 20 h period, independent of external urea concentrations. Thus, urea uptake is not via an active transport system. While hypotonicity caused oocytes to swell, vasopressin did not exert additional effect. Under hypotonic conditions, distribution ratios of water and urea changed in different ways supporting the view that distinguishable channels (pathways) were involved. It appeared that no correlated changes due to vasopressin occurred under osmotic challenge. The response pattern to vasopressin was different between renal epithelia and frog oocyte. PMID- 7875033 TI - Effects of somatostatin-28 on rat locus coeruleus neurons. AB - The effects of somatostatin-28 (SS-28) on rat locus coeruleus (LC) neurons were investigated with techniques of brain slice and intracellular recording. SS-28 was applied by micropressure ejection through a micropipette. SS-28 (500 microM, 10 or 20 psi, 1 msec - 5 sec) reversibly decreased the firing rate of all neurons of the locus coeruleus tested. In addition to inhibition of spontaneous firing, larger concentrations of SS-28 also hyperpolarized the neurons of the locus coeruleus and simultaneously decreased the input resistance. At the greatest concentration (20 psi x 5sec) applied, SS-28 produced complete inhibition of firing of all neurons tested; the inhibition was associated with a 11-mV hyperpolarization and decreased input resistance 9 percent. The voltage-current relationship of the resting cell revealed an inward-going rectification that became enhanced after the pressure application of SS-28. The reversal potential for the SS-28-induced hyperpolarization was -116 mV, which is approximately the potassium equilibrium potential. The results also showed that BaCl2 blocked the SS-28-induced hyperpolarization, but apamin did not. We conclude that the inhibitory actions of SS-28 are due to opening the inward-going rectification potassium channels and that SS-28 and somatostatin-14 exert similar electrophysiological actions on LC neurons. PMID- 7875034 TI - Optical and mathematical corrections of micropipette measurements of red blood cell geometry during anisotonic perifusion. AB - Accurate knowledge of red blood cell (RBC) membrane surface area and cellular volume is critical to understanding the geometric factors that affect RBC deformability. A useful method to determine RBC geometry is via micropipette aspiration in which the cell partially enters the tip of a glass pipette with a diameter of about 2 microns. Measurement of the cell while in the pipette allows calculation of cell geometry, but such measurements are subject to several artifacts. Herein, we analyze the effects of three artifacts on calculated RBC geometry during experimental osmotic manipulation. 1) The pipette internal diameter, as measured optically, requires correction for refractive index and focusing errors; 2) the pipette barrel is tapered rather than cylindrical; 3) the observed RBC outline is affected by a diffraction phenomenon. These optical and mathematical errors were all found to influence the calculated RBC geometry; both absolute values and relative changes during osmotic manipulation were affected. For RBC in isotonic medium, use of the above corrections significantly (p < 0.001) reduced the calculated area by 3.7%, the volume by 7.0%, and the minimum cylindrical diameter by 3.9%. The calculated membrane area dilation for cells exposed to hypotonic media was also significantly reduced; at 200 mOsm, the dilation was 2.8% +/- 0.2% without correction vs. 1.5% +/- 0.2% when all corrections were employed (p < 0.01). We therefore suggest that micropipette aspiration of RBC requires use of these correction techniques to obtain accurate values for RBC geometry and that such correction methods are of particular importance when RBC of different sizes are compared. PMID- 7875035 TI - Fluorescein derivatization of fibrinogen for flow cytometric analysis of fibrinogen binding to platelets. AB - Dog and human fibrinogen were derivatized with N-hydroxysuccinimido-fluorescein and utilized for flow cytometric estimation of fibrinogen binding to activated platelets. Fluorescein-fibrinogen binding fulfilled the criteria for specific binding to platelets; the binding was saturable, dependent on agonist activation, and inhibited by unlabeled fibrinogen. In addition, EDTA and barbourin, a KGD containing peptide, were found to inhibit the binding of fluorescein-fibrinogen. Fluorescein-fibrinogen bound to dog platelets with an apparent affinity of 0.31 microM after stimulation with either adenosine-5'-diphosphate (ADP) or plateletactivating factor. The labeled fibrinogen was also used to study the fibrinogen binding capacity of aged, biotinylated platelets. Aged platelets were indistinguishable from young platelets with regard to fibrinogen binding in response to ADP. These studies document that direct derivatization of fibrinogen with fluorescein generates a useful probe for analyzing fibrinogen binding to platelets with flow cytometry. PMID- 7875036 TI - Evaluation of a flow cytometric fluorescence quenching assay of phagocytosis of sensitized sheep erythrocytes by polymorphonuclear leukocytes. AB - A number of reports have been published describing phagocytosis assays for flow cytometric analysis. In some of these, the fluorescence quenching technique has been used to discriminate between adherent and ingested particles. In this report, we have evaluated the efficacy of a quantitative fluorescence quenching technique with crystal violet and trypan blue for application in a phagocytosis assay with polymorphonuclear leukocytes and sensitized sheep red blood cells. We set the requirements to a high quenching efficiency of the fluorescence of extracellularly bound particles and no intracellular quenching. The latter was determined using polymorphonuclear leukocytes stained with the fluorescent nuclear dye hydroethidine. We observed that both trypan blue and crystal violet efficiently quench the fluorescence of PKH26 (a red fluorescent membrane associated dye) erythrocytes but that only crystal violet quenches intracellular fluorescence. In testing trypan blue and crystal violet from different manufacturers, there was no real difference between different brands of crystal violet, but only the trypan blue from Merck turned out to be an efficient quencher, whereas the other brands of trypan blue showed low quenching efficiency. Trypan blue at a concentration of 25-50 micrograms/ml proved to be a good quencher of the fluorescent erythrocytes and exerted minimal side effects: over 90% quenching of the erythrocytes, no intracellular quenching, moderate increase in autofluorescence of the polymorphonuclear leukocytes, and no cell loss. PMID- 7875037 TI - Staining of Escherichia coli for flow cytometry: influx and efflux of ethidium bromide. AB - In an attempt to develop procedures for nucleic acid staining of bacteria for clinical routine assays, the uptake of ethidium bromide (EB) in wild-type Escherichia coli was studied using flow cytometry. Phosphate-buffered saline (PBS) containing EDTA or Tris significantly increased the net uptake of EB compared to PBS only. However, in the majority of the cells, the net uptake reached a constant level that was only a few percent of that of fully permeabilized cells, apparently due to the activity of a metabolically driven efflux pump. When cells were exposed to cold shock (0 degrees C for 30 min) in the presence of Tris or EDTA, the net uptake of dye was similar to that of fully permeabilized cells, whereas it was about half that value in PBS. When cold shock was given in growth medium, the cells split up into four subpopulations, with a net dye uptake ranging from that of fully permeabilized cells to less than 1% of that value. As expected, metabolic inhibitors (Na-azide, 2-deoxy-D-glucose, and CCCP) reduced efflux activity. However, fluorescence of metabolically inhibited cells never exceeded more than about half the value of that of dead cells, possibly reflecting conformational changes in DNA structure as a result of cell death. PMID- 7875038 TI - Detection of bromodeoxyuridine incorporation by alteration of the fluorescence emission from nucleic acid binding dyes using only an argon ion laser. AB - A method was developed that uses paired DNA dyes to detect the incorporation of bromodeoxyuridine (BrdUrd) into cellular DNA and requires only 488 nm excitation. The fluorescence of thiazole blue, TO-PRO-3, and LDS-751 was found to be enhanced by the presence of BrdUrd in DNA. Pairing LDS-751, thiazole blue, or TO-PRO-3 with propidium iodide (PI) for flow cytometry allowed the differentiation of cells containing BrdUrd from BrdUrd unlabeled cells. LDS-751 can be excited directly at 488 nm, and TO-PRO-3 or thiazole blue can be excited indirectly by resonance energy transfer from PI. The enhancement of fluorescence from these dyes is correlated with a decrease in PI fluorescence, suggesting an increased energy transfer from PI to the red emitting dye. Fluorescence from other dyes, including thiazole orange, TO-PRO-1, rhodamine 800, oxazine 750, and 7 aminoactinomycin D, was not altered by the presence of BrdUrd in DNA. Results also were obtained showing that BrdUrd detection using PI and TO-PRO-3 is compatible with immunofluorescence staining with FITC-labeled antibodies. PMID- 7875039 TI - Bladder irrigation specimens assayed by fluorescence in situ hybridization to interphase nuclei. AB - Bladder irrigation specimens provide a sampling of the entire bladder urothelium and are the most practical sample for longitudinally monitoring patients. This study presents cross-sectional fluorescence in situ hybridization (FISH) analyses with correlated DNA cytometry data on 76 patients monitored for recurrent bladder tumors. FISH probes complementary to centromeric satellite sequences for chromosomes 1, 7, 9, 11, 15, and 17 were used. Aberrations in copy number were observed for chromosomes 1, 7, 11, and 17 principally in patients with aneuploid tumors. Monosomy of chromosome 9 was observed in 39% of the diploid and 31% of the specimens with high hyperdiploid fraction. Significantly, 24% of patients with a history of bladder cancer but with no clinical evidence of disease exhibited monosomy of chromosome 9. This suggests a persistent and significantly large population of abnormal cells in the absence of clinical evidence of disease. Loss of chromosome 9 relative to DNA ploidy was observed in 24% of patients with no evidence of disease, in 59% of patients with tumor, and in 79% of patients with histologically confirmed transitional cell carcinoma, grades 1 3. Loss of chromosome 15 was also observed in a large percentage of patients. Loss of chromosome 15 was observed in 41% of specimens from patients in whom no tumor was seen, in 38% of specimens from patients with tumor, and in 67% of specimens from patients with histologically confirmed transitional cell carcinoma. Results of this study document the use of bladder irrigation specimens as a specimen source for FISH analyses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875040 TI - Carcinoma in situ of the testis detected by DNA flow cytometry of testicular fine needle aspirates. AB - Testicular carcinoma in situ (CIS) is usually diagnosed histologically on surgical biopsies. The present study was performed to test an alternative approach--DNA flow cytometry (FCM) of testicular fine-needle aspirates (FNA)--for the detection of this lesion. FNAs from 18 cases of testicular germ cell tumors (TGCT) and tumor adjacent parenchyma were analysed by DNA FCM. DNA histograms of all cell nuclei and histograms representing selectively the hyperdiploid compartment were analysed. The presence and extention of CIS were determined by histology and immunohistochemistry. In 16 of 18 cases, CIS was histologically present, whereas aneuploid peaks were detected in only 11 cases in DNA histograms of all cell nuclei. In the analysis of the histograms of the hyperdiploid region, 4 additional cases of CIS could be identified increasing the sensitivity to 15/16 cases (93.8%). In all but one case, the DNA indices of CIS and invasive tumors were identical. The study demonstrates that DNA FCM of testicular FNAs using the described data acquisition and analysis could also be applicable for detection of CIS in a clinical situation. PMID- 7875041 TI - Display and correction of flow cytometry time-dependent fluorescence changes. AB - The resolution of measurements of cellular attributes by flow cytometry, based on differences in labeling by fluorescent markers, may be affected by variations in staining and sample stream flow that can occur during the course of data acquisition. We describe a method of display and correction of time-dependent changes by looking at the list mode data in chronological order. PMID- 7875042 TI - Constitutive expression of P-glycoprotein as a determinant of loading with fluorescent calcium probes. AB - Determination of intracellular calcium levels in Chinese hamster ovary (CHO) cells using the fluorescent calcium probe indo-1AM was hindered by the low level of accumulation of indo-1 in these cells. CHO cells are known to express basal levels of the multidrug resistance efflux pump P-glycoprotein (P-gp). Rhodamine 123, which is a known substrate of P-gp, was used to confirm the presence of P-gp in CHO cells. Verapamil and cyclosporin (CsA), both inhibitors of P-gp, enhanced accumulation of indo-1 in these cells and therefore allowed for improved intracellular calcium measurements. P-gp overexpressing colchicine-resistant CHO cells (CHRC5) also displayed enhanced indo-1AM loading with P-gp inhibitors. Nondetectable levels of P-gp activity were found in wild-type CEM-CCRF cells (human T lymphoblasts), and these cells did not show any difference in indo-1AM loading in the presence or absence of P-gp inhibitors. Loading of a second calcium fluorescent probe fluo-3AM was improved in CHO cells by P-gp inhibition, whereas the structurally related pH probe BCECF-AM was minimally affected. Because low levels of P-gp may be expressed by a range of cell lines and normal tissues, it is suggested that this be considered if difficulties are encountered in loading fluorescent calcium probes. PMID- 7875043 TI - Optimizing the detection of cell surface antigens on elicited or activated mouse peritoneal macrophages. AB - Blocking conditions that are optimal for the detection of surface antigens on resident peritoneal macrophages (PM phi) by flow cytometry are not ideal for elicited or activated PM phi. A blocking step of 10% goat serum can be used routinely to detect the F4/80 and Mac-1 antigens on resident PM phi. In contrast, high concentrations (33-50% each) of combined goat and mouse sera were required to reduce nonspecific binding and to improve the detection of the F4/80 antigen on PM phi elicited by thioglycollate broth (TG) or activated by maleic anhydride divinyl ether copolymer (MVE-2). However, even low concentrations of goat serum masked the expression of the Mac-2 antigen on TG and MVE-2 PM phi. Thus, within a given elicited or activated PM phi population, different blocking conditions may be necessary to detect different surface antigens optimally. In addition to blocking, the use of isotypic controls that match the monoclonal antibody isotypes was found to be necessary for the optimal detection of antigen expression on TG and MVE-2 PM phi. PMID- 7875044 TI - Low-molecular-weight (tubular) proteinuria is not related to glycaemic control in non-insulin dependent diabetes mellitus. AB - Early morning urine specimens were obtained from two groups of non-insulin dependent diabetic patients and a group (43 subjects) of normal controls. The diabetic patients were divided into two subgroups according to the degree of diabetic control as judged by their glycosylated haemoglobin (HbA1) levels (well controlled, 47 subjects; poorly controlled, 51 subjects). The concentration of the low-molecular-weight enzyme (lysozyme) was determined in each urine specimen and related to the concentration of creatinine (lysozyme/creatinine). The mean urinary lysozyme concentration was higher in each of the two diabetic groups as compared with the control group. However, it was not significantly different between the two diabetic groups. These result suggest that there is no association between the degree of glycaemic control and tubular proteinuria. PMID- 7875045 TI - Red cell sodium-lithium countertransport and blood pressure in children with insulin-dependent diabetes mellitus. AB - Sodium-lithium countertransport and blood pressure responses, maximal elevated plasma norepinephrine concentrations induced by acute physical work load and the carbohydrate metabolic state were analyzed in 40 children suffering from insulin dependent diabetes mellitus (IDDM). Patients were selected according to the duration of the disease to get a horizontal insight into the progression of the diabetes. Sixteen healthy children served as controls. Sodium-lithium countertransport (Na-Li CT) was 281 +/- 64 mumol/l red blood cells (RBC) per hour in the control group. Na-Li CT was elevated in all diabetic groups (newly diagnosed: 455 +/- 48; diabetics for 5-7 years: 495 +/- 48; diabetics for 10-13 years: 470 +/- 36). Plasma norepinephrine concentration increased during physical exercise, the elevation was more pronounced in diabetic children being 13.5 +/- 10.4, 10.1 +/- 5.0 and 12.3 +/- 5.4 nmol/l in the three diabetic groups, respectively, which differed significantly from that of controls (7.94 +/- 2.9; P < 0.01). Systolic blood pressure increased significantly during physical exercise in each group. However, maximal elevated systolic blood pressure was higher in children who had diabetes for more than 10 years than in controls (158 +/- 11 vs. 137 +/- 9.7 mmHg; P < 0.001). Na-Li CT correlated positively with the maximal systolic blood pressure measured during physical exercise in those diabetic children who suffered from diabetes for more than 5 years. High activity of Na-Li CT in combination with elevated blood pressure and high plasma concentration of norepinephrine induced by acute physical exercise may represent a risk of renal/vascular complications in patients suffering from IDDM. PMID- 7875046 TI - Cold pressor test in diabetic autonomic neuropathy. AB - The tests for evaluating sympathetic dysfunction seen in diabetic patients are few and insensitive. For this reason, there are some difficulties in diagnosing sympathetic dysfunction and additional tests are required. The cold pressor test causes a strong sympathetic stimulus and this study investigated whether this test could be helpful in diagnosing sympathetic dysfunction. The cold pressor test was applied to a group of diabetic patients (n = 33) and a control group (n = 15). The mean systolic cold pressor response in diabetic patients was found similar to controls (9 +/- 1.4 vs. 10.6 +/- 1.2 mmHg). However the mean diastolic cold pressor response was significantly lower in diabetic patients as compared with the control group (7.7 +/- 1.0 vs. 12.0 +/- 1.1 mmHg, P < 0.05). Cardiovascular reflex tests were also applied to diabetic patients and deep breathing and orthostatic hypotension test results were used to categorize the patients with parasympathetic and/or sympathetic dysfunction. In patients with autonomic neuropathy the diastolic cold pressor response was smaller than the controls (6.9 +/- 1.3 vs. 12.0 +/- 1.1 mmHg, P < 0.05); however, in patients without autonomic neuropathy it was not significantly different from controls (8.7 +/- 1.8 vs. 12.0 +/- 1.1). The systolic cold pressor test results showed no difference between patients with or without parasympathetic dysfunction but diastolic cold pressor results in patients with sympathetic dysfunction were significantly lower than the results of the patients without sympathetic dysfunction (3.8 +/- 1.3 vs. 9.1 +/- 1.3 mmHg, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875047 TI - Complaints of neuropathy related to the clinical and neurophysiological assessment of nerve function in patients with diabetes mellitus. AB - To determine the value of a detailed evaluation of neuropathic sensory complaints in assessing diabetic polyneuropathy, a questionnaire listing different sensory symptoms was compared with a clinical and neurophysiological examination of the peripheral nerves. Thirty-seven insulin dependent and thirty-one non-insulin dependent diabetic patients who were consecutively referred because of suspected polyneuropathy were investigated. In all patients both clinical and neurophysiological examination confirmed the diagnosis of polyneuropathy. Only the scores of the clinical examination were significantly correlated with the scores of the sensory symptoms (r = 0.31, P < 0.01). Using a factor analysis, a dimension of complaints of sensory alteration could be distinguished from a dimension of complaints of neuropathic pain (alpha coefficients 0.88 and 0.86, respectively). Tingling sensations turned out to be an expression of the dimension of complaints of sensory alteration. The scores of clinical and neurophysiological examinations were only significantly correlated with the dimension of sensory alteration (r = 0.38, P < 0.002; r = 0.37, P < 0.02, respectively). We conclude that only symptoms of numbness and tingling sensations in hand and feet are associated with objectively assessed diabetic polyneuropathy. PMID- 7875048 TI - No association between anti-bovine serum albumin antibodies and islet cell reactive antibodies in newly diagnosed type 1 diabetic patients. AB - Serological findings have suggested that antibodies (Ab) to bovine serum albumin (BSA-Ab) are associated with type 1 diabetes mellitus. The aim of our study was to evaluate a competitive fluid-phase radioimmunoassay for detecting BSA-Ab using different incubation times and to study a possible association of these BSA antibodies with autoantibodies (AAb) frequently detected in type 1 diabetic patients. For the overnight incubation time, there was an enormous overlap in the [125I]BSA binding by serum samples between 52 newly diagnosed type 1 diabetic patients (mean [125I]BSA binding 23.6 +/- 17.4%) and 54 healthy blood donors (mean [125I]BSA binding 10.2 +/- 15.7%). By an incubation time of only 3 min the BSA-antibody prevalence was found to be 15.4% (8/52) for type 1 diabetic patients and 3.7% (2/54) for control subjects. However, there was no association between BSA-Ab and type 1 diabetes-associated antibodies as cytoplasmic islet cell antibodies (ICA), or glutamate decarboxylase autoantibodies. Our results confirm that (i) BSA-Ab occur more frequently in newly diagnosed type 1 diabetic patients compared with a healthy control group and (ii) that the BSA-Ab detected by the fluid-phase radioimmunoassay with an incubation time of 3 min are more disease associated than the [125I]BSA binding after an overnight incubation. The competitive BSA-Ab fluid-phase radioimmunoassay described is a simple and rapid method to detect antibodies specifically reactive with BSA. It is suggested that the humoral immune reactivity to BSA in type 1 diabetic patients probably reflects an unspecific defect of the immune system and gives no additionally diagnostic value about the type 1 diabetes. PMID- 7875049 TI - Circadian blood pressure variation in non-insulin-dependent diabetes mellitus with nephropathy. AB - We studied a circadian blood pressure variation in relation to the progression of diabetic nephropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). Age, duration of diabetes, body mass index and glycemic control did not differ among the groups of patients with normo-, micro- and macroalbuminuria. None of the patients received antihypertensive drugs. There were no differences in renal and autonomic functions between normo- and microalbuminuric groups, but these functions were impaired in the macroalbuminuric group. The rise in blood pressure was more apparent in 24-h ambulatory blood pressure (AMBP), especially during night-time, as compared with casual blood pressure. Such blood pressure rise was in accordance with the progression of nephropathy. However, pulse rate did not differ among the three groups. The nocturnal fall in blood pressure was blunted in the micro- and macroalbuminuria groups, but evident in the normoalbuminuric group. In the latter, daytime systolic blood pressure (SBP) was significantly higher than night-time SBP (123 +/- 5 mmHg vs. 113 +/- 3 mmHg, P = 0.002). In contrast, in the former two groups of patients, there were no significant differences in SBP between daytime and night-time (134 +/- 9 mmHg vs. 134 +/- 9 mmHg, ns, for microalbuminuria and 159 +/- 8 mmHg vs. 165 +/- 7 mmHg, ns, for macroalbuminuria). Urinary albumin excretion was significantly correlated with night-time SBP (r = 0.48, P = 0.015), but not with daytime SBP (r = 0.30, ns).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875050 TI - Serum insulin is a risk marker for coronary heart disease mortality in men but not in women. AB - Serum insulin 1 h post-glucose load is examined in this prospective study of 2971 Caucasoid subjects aged > 20 years in 1966 and followed to 1989. The serum insulin levels as a continuous variable show no significant linear association with coronary heart disease (CHD) deaths in either sex after accounting for age by Cox proportional hazards analysis. In males the quintile classes of serum insulin show a striking U-shaped pattern with both the highest and lowest quintiles having significant associations with CHD deaths. In females the insulin quintiles show no direct association. Analysis for interactions of risk variables indicate that in females the relative protection of low cholesterol levels is abolished by hyperinsulinaemia after 12 years. Thus, serum insulin is not a direct aetiological risk factor for CHD. The findings suggest that the associations are likely to be due to confounding effects of unmeasured variables including lipid subfractions. PMID- 7875051 TI - Infrared pupillometry in the assessment of autonomic function. AB - In order to study normal dynamic pupillary function and to determine reference limits for various pupillary variables, 81 healthy subjects aged between 32 and 60 years were examined using a portable infrared pupillometer. Additionally, 36 patients with type I diabetes mellitus were studied. In healthy subjects, sex had no, or only marginal, effect on the responses. Body mass index or smoking habits had no effect on pupillary dynamics. The relative reflex amplitude (RRA) was independent of age. The time to minimum diameter tmin was dependent on maximum constriction velocity (MCV) (P < 0.001) but not on age, initial diameter or reflex amplitude (RA). The MCV, maximum redilatation velocity (MRV) and time to 75% redilatation (t75%) were strongly dependent on RRA (P < 0.001 for each), but age had no or only a marginal effect. No correlation existed between the results of pupillometry and those of Valsalva or deep breathing tests. The lowest normal value for RRA was 29%. The reference limits for MCV, MRV and t75% were calculated in relation to RRA. The smaller the RRA was, the slower the velocities and the shorter the t75% were. Using these reference limits, 25% of the diabetic patients without cardiac autonomic neuropathy and 50% with definite cardiac autonomic neuropathy had abnormalities in at least one out of four pupillary variables. It is concluded that infrared pupillometry may be a useful additional method for the assessment of autonomic function. PMID- 7875053 TI - Synthesis and antitumour activities of tetracyclic quinolone antineoplastic agents. AB - DNA topoisomerases, found in all prokaryotic and eukaryotic cells, play a key role in controlling the topological state of DNA. They are involved in DNA replication, RNA transcription and recombination affecting cell proliferation. Quinolone antibacterial agents have been shown to be inhibitors of DNA gyrase, a bacterial topoisomerase II enzyme. The eukaryotic topoisomerase II is the target of various cytotoxic agents such as adriamycin and etoposide. Due to the mechanistic similarities and sequence homologies shared by both bacterial and mammalian DNA topoisomerase II, we initiated a screening programme to search for quinolones as antitumour agents and reported the identification of a new class of quinolone, quinobenoxazines, having excellent in vitro cytotoxic activity comparable to adriamycin. In the continuation of this research work, we synthesized a series of amino-substituted quinobenoxazines and found that some of them possess more potent in vitro cytotoxicity than the parent unsubstituted quinobenoxazines. The chemical synthesis as well as biological properties of these tetracyclic quinolones are described. PMID- 7875052 TI - Bimodal effect of transforming growth factor-beta on insulin secretion in MIN6 cells. AB - The effects of transforming growth factor-beta (TGF-beta) on insulin secretion were investigated using a glucose-responsive clonal cell line, MIN6. One hundred pM TGF-beta stimulated insulin release during 0.5-24 h of incubation in the presence of 5.5 mM glucose, but not after 48 h; 1 nM TGF-beta also stimulated insulin release up to 2 h of exposure, but the effect was not seen after 6 h of exposure. When cells were incubated with 25 mM glucose for 24 h, 100 pM TGF-beta significantly inhibited glucose-stimulated insulin release, whereas insulin release was not altered at 0 or 2.8 mM glucose. On the contrary, forskolin- (10 microM) and tolbutamide- (40 microM) induced insulin release were not affected by TGF-beta. TGF-beta affected neither the cell growth nor the cellular insulin content. An addition of 1 microM nitrendipine abolished TGF-beta-induced insulin secretion at 5.5 mM glucose. The presence study shows that TGF-beta exerts a bimodal effect on glucose-induced insulin secretion from MIN6 cells, depending on dose, time of exposure and concentrations of coexisting glucose. These effects might be mediated by the Ca(2+)-dependent mechanism. PMID- 7875054 TI - Lipid peroxidation and survival in rats following cerebral post-ischaemic reperfusion: effect of drugs with different molecular mechanisms. AB - In the present study the authors investigated the effect of pretreatment with exogenous antioxidants such as deferoxamine (iron chelating drug), allopurinol (competitive inhibitor of xanthine oxidase) and vitamin E (scavenger of oxygen free radicals) on lipid peroxidation in rat cerebral cortex after post-ischaemic reperfusion, and on the survival rate. The effect of pretreatment with two calcium-antagonist drugs (diltiazem and verapamil) was also evaluated under the same experimental conditions. Pretreatment with exogenous antioxidants and with calcium-antagonist drugs significantly decreased cerebral conjugated diene levels (index of lipoperoxidation) with a concomitant increase in survival with respect to untreated ischaemic rats. PMID- 7875055 TI - L-propionyl carnitine protects erythrocytes and low density lipoproteins against peroxidation. AB - The effects of peroxidation on the erythrocytes of rats orally treated with L propionyl carnitine for 15 days (50 mg/kg/day) were investigated. Peroxidation was produced by incubating the cells in the presence of the cytotoxic system: lactoperoxidase-hydrogen peroxide and iodide ions. Lysis of erythrocytes was evaluated by measuring the turbidity following the decrease in absorbance at 600 nm. The 50% of erythrocyte lysis of untreated animals was observed after 16 min and in about 30 min all the cells were lysed. With L-propionyl carnitine-treated rat erythrocytes the time at which 50% of lysis was observed increased to 23 min. L-propionyl carnitine also exerted its protective effect in vitro when incubated with untreated rat erythrocytes or human erythrocytes in the presence of the cytolytic system. The presence of L-propionyl carnitine in the incubation mixture markedly decreased the malonaldehyde formation. The protection was concentration dependent. To establish if L-propionyl carnitine protects from oxygen reactive species or is able to stabilize the damaged membranes, a latent damage was produced by incubating the erythrocytes with the cytolytic system for a few minutes. The cells were then removed and suspended in buffered saline in the absence or in the presence of different L-propionyl carnitine concentrations. L propionyl carnitine decreased the velocity of lysis of damaged erythrocytes. These data suggest that L-propionyl carnitine protects erythrocytes from oxygen reactive species and also stabilizes the damaged membrane probably by specific binding with protein and/or phospholipid domains. Low density lipoproteins (LDLs) from human blood were peroxidized by exposure to Cu2+ ions in the presence of various L-propionyl carnitine concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875056 TI - Dextrorphan and dextromethorphan: comparative antitussive effects on guinea pigs. AB - Dextromethorphan, after administration, is rapidly and extensively transformed into dextrorphan. The aim of this study was to compare the cough-suppressing activity of 6, 12, 24, 48 mg/kg, i.p., of dextrorphan (dextro rotatory isomer of racemorphan) with that of dextromethorphan, using the model of citric acid induced coughing in the unanaesthetized, unrestrained guinea pig. A significant dose-effect relationship of dextrorphan in reducing citric acid-induced cough was observed. This effect was comparable with that of dextromethorphan. However, at 48 mg/kg, i.p., dextromethorphan had a toxic effect while dextrorphan did not. Because dextrorphan is the major metabolite of dextromethorphan and has antitussive activity comparable to that of dextromethorphan, clinical use of dextrorphan is suggested. PMID- 7875057 TI - A prospective study in healthy volunteers of the topical absorption of a 5% rifaximin cream. AB - Rifaximin, the active ingredient of an antibiotic cream, is a synthetic antibiotic derived from rifamycin and characterized by minimal absorption. In animals, no absorption was detected after topical application on the skin. The question as to whether there is detectable absorption in man by the same administration route is answered by this study in healthy volunteers. One gram of the cream containing 5% rifaximin was massaged on a sizable surface of skin prepared prior to application by mechanical abrasion. Rifaximin concentrations in blood and urine were then determined by means of HPLC-electrochemical coulometrical detection. Concentrations in all samples being less than 2.5 ng/ml, the method's limit of detection, it is concluded that there is no detectable absorption in man. No adverse reactions were reported during this one day study. The results confirm studies performed in animals which showed that rifaximin is not absorbed and is well tolerated. PMID- 7875058 TI - Oral ciprofloxacin versus intravenous therapy with other non-quinolone agents: a study of 291 infections. AB - A retrospective comparison of oral ciprofloxacin in mono- or combination therapy versus standard intravenous (i.v.) therapy with non-quinolone agents was undertaken to evaluate efficacy and cost in actual clinical practice. The choice, dose and duration of antibiotic therapy was determined solely by the patients' physicians. The patients were treated for infections of the lower respiratory tract; urinary tract and skin (totalling 291 infections). The most frequent species isolated were Escherichia coli (21.6%), Staphylococcus aureus (12%), and Pseudomonas aeruginosa (11.7%). No significant differences (p > 0.10) in the cure rates and duration of infection were observed when comparing oral ciprofloxacin only, versus standard i.v. therapy. The administration of simultaneous combination therapy resulted in a lower cure rate and longer infection, regardless of the site of infection. The duration of therapy required to show a cure or improvement was significantly shorter (p < 0.0001) for oral ciprofloxacin alone, than for i.v. therapy and ciprofloxacin combination therapies. PMID- 7875059 TI - Hazard evaluation of Army compounds in the environment. PMID- 7875061 TI - Environmental xenobiotics: safe disposal of chemicals damaged during warfare. PMID- 7875060 TI - Contamination of the air with mineral fibers following the explosive destruction of buildings and fire. AB - Mineral fibers, including asbestos, are ubiquitous contaminants of the environment. Asbestos fibers are generally present at levels below 1 fiber/L in air though 10 fibers/L may be found in cities; these levels do not appear to be high enough to present a hazard to health. These fibers come mostly from the use of fibrous materials as thermal and acoustic insulation in buildings, and their use as friction materials. Historically, occupational air levels were often very high and as a result there was a high incidence of fibrosis and also cancer in exposed workers, mostly among those in the industries concerned with the winning or processing of asbestos fiber. Levels high enough to produce disease have also occurred paraoccupationally in the families of asbestos workers. The effect of fire and explosion in a building is to disrupt its structure and vastly increase the level of airborne fiber for a considerable distance (kilometers) around it. Air levels of fiber can remain high for months, and as a result the earliest occupational experiences are likely to be repeated. The greatest danger is from exposure to blue and brown asbestos, and it is known that even a single high exposure can be responsible for the development of a tumor decades later. PMID- 7875062 TI - Ranking the carcinogenic potential of chemical mixtures: the integral search system and its use in evaluating hazardous waste sites. PMID- 7875063 TI - Toxic effects and a structure--property study of organic explosives, propellants, and related compounds. PMID- 7875064 TI - The effects of nutrition on chemical toxicity. PMID- 7875065 TI - Metabolism of chloramphenicol: a story of nearly 50 years. PMID- 7875066 TI - [The value of systematized follow-up studies after resection of a stomach carcinoma]. AB - A retrospective study of the possible value of standardized follow-up examinations was undertaken in a group of 251 patients (163 men, 88 women; mean age at diagnosis 58 [33-78] years) who had undergone putatively curative gastric resection for adenocarcinoma between 1.1. 1978 and 31. 12. 1987 and had survived at least 3 months after the operation. 113 patients (45%) regularly had follow-up examinations according to a standardized diagnostic protocol, 67 (27%) only irregularly, while 71 (28%) had none. Follow-up examination revealed tumour recurrence in 53 patients (30%), which in 18 (34%) was still asymptomatic. In one of these patients resection of the recurrence was again undertaken with curative intent, a palliative operation was performed in five, chemotherapy in seven, three received radiotherapy and 37 were treated purely symptomatically. The results do not indicate that the survival rate was improved by the standardized follow-up protocol and it is concluded that symptom-oriented and individualized follow-up examination without standardized protocol is sufficient in this type of case, except for scientific purposes. PMID- 7875067 TI - [Closure of an atrial septum defect using an umbrella prosthesis]. AB - About three and a half years after direct suture of a secundum atrial septal defect (ASD) the now 72-year-old patient developed heart failure with pulmonary congestion and pleural effusion which responded to medical treatment. The electrocardiogram showed atrial fibrillation with an irregular ventricular rate and right bundle branch block. Right heart catheterization established recurrence of the ASD with a left to right shunt of 60% (Qp/Qs = 2.5) and a pulmonary artery pressure of 45/12 mmHg. Because of the clinical state, the risk of re-operation and the suitable anatomy, non-operative percutaneous transvenous catheter closure of the defect with a double-umbrella device was indicated. Following this procedure the cardiomegaly regressed, while colour-Doppler echocardiography demonstrated a minimal residual left to right shunt. The pulmonary artery pressure had fallen to 32/13 mmHg. Three months later the patient was without symptoms and resumed her usual activity. The ECG now showed sinus rhythm, and there was no evidence of a shunt. Anticoagulation with acetyl salicylic acid (100 mg daily) was continued for 3 months. PMID- 7875068 TI - [Oral contraceptive-induced pancreatitis in the hyperchylomicronemia syndrome]. AB - A now 24-year-old woman was found at the age of 2 years to have an hyperchylomicronaemia syndrome due to lipoprotein lipase deficiency: the triglyceride level was then 6000 mg/dl. But in subsequent years it had been reduced to between 550 and 2600 mg/dl by dieting. There were no xanthomas or abdominal symptoms during those years. When aged 20 years she was put on oral contraceptives (one-phase preparation: 0.03 mg ethinylestradiol and 0.075 gestodene). Six months later she had the first attack of severe necrotizing pancreatitis; three more attacks followed in the subsequent 6 months. All four attacks occurred during the drug-free period of the menstrual cycle. The relationship with contraceptive intake was not established until the fourth attack. The last acute pancreatitis (lipase 3283 U/l amylase 595 U/l, triglyceride 2400 mg/dl, WBC count 13,899/microliters; ultrasonography revealed fluid swelling and necrotic areas, especially around the splenic hilus) regressed within 5 days and has not recurred for 3 years after the patient stopped taking oral contraceptives. On a diet the triglyceride level has been around 880 mg/dl. PMID- 7875070 TI - [Driving fitness of elderly people with dementia and/or movement disorders]. PMID- 7875069 TI - [Anaphylactoid side effects of drugs]. PMID- 7875071 TI - [The "assisted-death" decision of the Federal court on 13 September 1994]. PMID- 7875072 TI - [Candidiasis of the intestines]. PMID- 7875073 TI - ["White Addison's disease" as an intensive care emergency]. PMID- 7875074 TI - [Patient-oriented drug information]. PMID- 7875075 TI - [Hypocalcemic crisis]. PMID- 7875076 TI - [Ullrich-Turner syndrome]. PMID- 7875077 TI - [Doppler sonographic evaluation of the effectiveness of an antirejection treatment after kidney transplantation]. AB - Data on 64 rejection reactions in 108 consecutive patients after renal transplantation (61 males, 47 females; mean age 42.8 +/- 12.9 years) were analysed to test what Doppler sonographic measurements can be used to predict whether a given drug regimen is able to suppress rejection. Results were compared with renal function and histological evidence of rejection. The >> pulsatility index << (PI), which is dependent on flow resistance, was determined by Doppler echocardiography: it increases on rejection (measurements made 2.0 +/- 1.1 days apart). The rejection reaction was successfully controlled by drugs (methylprednisolone, azathioprine and cyclosporin) in 44 patients (group 1), but not in 20 patients (group 2). PI before rejection (group 1: 1.8 +/- 0.5; group 2: 1.7 +/- 0.6), PI during histologically confirmed rejection (2.6 +/- 1.2 and 3.1 +/- 1.4, respectively), the size of difference between these values, and parameters of renal function provided no pointers to any drug efficacy in suppressing rejection. But individual changes in PI during suppression treatment proved to be of outstanding value (P < 0.00005). Signs of florid rejection at the end of treatment period correlated with a rising PI in 13 of 17 rejection episodes, while PI fell in only 7 of 47 episodes. Vascular signs of rejection tended to be poor predictors of rejection (P .028). - These findings indicate that serial Doppler sonography can be helpful in monitoring antirejection treatment. PMID- 7875078 TI - [Implantable defibrillator in the long QT syndrome]. AB - A 29-year-old otherwise symptom-free patient had undergone a partial thyroidectomy 5 years ago followed by an episode of ventricular tachycardia and (after lidocaine injection) ventricular fibrillation requiring external defibrillation. No cause for the arrhythmias had been found at that time. Two subsequent syncopes led to her hospitalization. An asystole occurred while she was being monitored, and during the resuscitation there were several periods of ventricular fibrillation, which responded to external defibrillation. Subsequently several episodes of self-limiting ventricular tachycardia were recorded. A long QT syndrome with torsade-de-pointes tachycardia was diagnosed on the basis of typical ECG changes (QT interval 545 ms). Extensive diagnostic tests failed to find a cause. To prevent further tachycardias she was given propranolol, 40 mg three times daily, and an automatic defibrillator was implanted as a precaution. But no defibrillator discharge has so far been required (more than 10 months). PMID- 7875079 TI - [Brain and gallbladder metastases 10 years after local excision of a cutaneous malignant melanoma]. AB - A 52-year-old man had a generalized seizure resulting in fracture of two vertebrae 10 years after excision of a superficially spreading melanoma (Clark level III) on the left flank. Additional to pain on pressure over the right upper abdomen, the erythrocyte sedimentation rate was increased (41 mm) and the activity of the liver enzymes was raised. Neurological examination indicated a loss of short-term memory, signs of meningeal irritation, unsteady gait and falling tendency. Cerebrospinal fluid showed mild pleocytosis and cells suspicious of tumour. Upper abdominal ultrasonography revealed an enlarged gallbladder with contents of soft-tissue density. Magnetic resonance imaging showed numerous round lesions in the brain which looked nodular after contrast medium injection. Cholecystectomy revealed metastases of a malignant melanoma. It was likely that the cerebral lesions also represented metastases. The confusional state increased in severity. Neither cytostatic drugs nor radiotherapy were administered, because of the poor prognosis. The patient, now fully disoriented, died 54 days after hospital admission. PMID- 7875080 TI - [Current therapy for chronic viral hepatitis. The Viral Hepatitis Panel]. PMID- 7875081 TI - [Therapy-refractory angina pectoris. Pathophysiologic basis and evaluation of alternative therapies]. PMID- 7875082 TI - [Fitness for driving while on the "zero diet"]. PMID- 7875083 TI - [Ajmaline test in Wolff-Parkinson-White syndrome]. PMID- 7875084 TI - [Risk of D-lactate acidosis while receiving acarbose]. PMID- 7875085 TI - Choices in contraception. PMID- 7875086 TI - A comparative study of users of long-term contraceptive subdermal implants and female surgical contraception in Kenya. AB - This was a comparative study of users of Norplant contraceptive, Subdermal implants and LA Minilap, in rural, urban and peri-urban sites in Kenya during 1991-1993. Both methods are very well accepted by well counselled women seeking long-term, continuous, convenient, highly effective contraception. Norplant users had a mean age of 27.3 years, an average of 2.6 living children and 25.3 per cent were unmarried, while 32.9 percent had completed their families. This compares with 31.3 years, 6.2 living children, 0.6 percent unmarried and 100 percent completed families respectively for LA Minilap. Norplant acceptance rates have continued to rise over the few years since programme inception, and now stand at 5.4 percent of all new acceptors. LA Minilap acceptance trends shows a plateau or moderate down-turn at 21.6 percent of new acceptors. The possible reasons and implications of these observations, along with user characteristics are discussed. PMID- 7875087 TI - Acceptability of Norplant contraceptive subdermal implants in Kenya. AB - Norplant contraceptive implants are a relatively new acquisition onto the Kenyan family planning scene. The method seems highly acceptable to a wide cross-section of Kenyan women in government and non-governmental organisations (NGO) clinics. One thousand, six hundred and fifty four clients were recruited into the programme of the largest family planning NGO between 1991 and 1994. Most of the acceptors were young with an average number of 2.6 living children. Half-yearly acceptance rates have been rising. There were minimal serious side effects reported, but 72.0% of the clients complained of some menstrual disruption. Site infection rates were 0.2%, the same as capsule expulsion rates and benign ovarian cyst. Continuation rates were good at 91.0% over the first year and 80.0% over the second year. Client profile and user characteristics are presented. Norplant seems to be a well accepted contraceptive method by young low-parity Kenyan women seeking long-term, continuous yet reversible contraceptive options. PMID- 7875088 TI - Recognition of risk factors in pregnancy among women attending antenatal clinic at Mbagala, Dar es Salaam. AB - A study on the recognition of risk factors in pregnancy by pregnant women attending antenatal clinic (ANC) at Mbagala, Dar es Salaam, Tanzania was done. 203 women with ages ranging from 15-43 years were seen on their first visit. 32.51% were primigravidas while 67.5% were multiparous with parity varying from 2 13 deliveries. 32.5% had received no formal education; 13.4% had 1-6 years education, while 54.2% had 7-12 years of formal education. Most of the women did not know when in the course of pregnancy they should start ANC: 52% of the women booked and reported that the best gestational age for booking was in the second trimester. There was no definite answer as to why the women came for the 1st visit to the ANC at a particular gestational age. 5% of the women felt that a woman could start to have children between age 10-14 years. 62.1% thought a woman could start to have children between 15-20 years. 10.3% did not know when a woman could start to have children. Some of the risk factors identified at the clinic included: shortness, age below 19 (11.8%), age 35 and more than 4 deliveries (13.3%) and HB below 75%, malaria and hookworm (9.9%). It appears that pregnant women attending Mbagala ANC booked within the second and third trimester. Their knowledge regarding risk factors in pregnancy was very low. A comprehensive antenatal intervention programme should be introduced at Mbagala ANC to educate women on risk factors in pregnancy. It should be conducted through client oriented problem and need approach. PMID- 7875089 TI - Computed tomographic brain scan findings in Saudi epileptic patients. AB - Computed tomographic (CT) brain scan was performed on 142 consecutive epileptic patients of Saudi Arab extraction without clinical features of acute illness or a progressive neurological disorder at presentation. CT brain scan was normal in 56 patients (39%). CT scan was abnormal in 57 (73%) of 78 patients over 20 years of age compared with 29 (45%) of 64 younger patients (x2 = 11.3; p < 0.001); and in 25 (75%) of 36 patients presumed to suffer from symptomatic epilepsy on clinical grounds compared with 36 (46%) of 76 others with idiopathic epilepsy (x2 = 8.2; p < 0.01). Potentially treatable lesions were detected in 11 (8%) patients and congenital lesions in 9 (6%). Multiple lesions were present in the CT scan of 20 patients. Cerebral atrophy (CA), the commonest lesion detected, was present in 52 (37%) of 142 patients and 60% of 86 patients with abnormal CT scans. Diffuse CA was present in 21% of 78 patients over 20 years of age compared with 14% of 64 younger patients. Similarly, diffuse CA occurred in 25% of 48 patients with late onset epilepsy compared with 14% of 94 patients in whom seizures began before the age of 20 years. Our findings are in accord with those previously reported and underscore the need for selective and judicious use of CT scan facilities in epileptic patients. PMID- 7875090 TI - Relationship between household access to food and malnutrition in eastern and southern Africa. AB - This review paper gives an overview of the relationship between household access to food and malnutrition using national level data in the Eastern and Southern Africa Region. The overall prevalence of malnutrition amongst the under-five population have not changed significantly over the decade and, in some cases, have deteriorated. The situation of household access to food differs between economies and production systems, but most households (average of 80%) in the region do not have access to adequate food. A preliminary analysis of the determinants of malnutrition at country level pointed to the importance of: financial access to food (an indicator of household access to food) and; access to safe water (an indicator of household healthy environment), as the most significant variables predicting rates of malnutrition. Several areas for action by governments in the region and for further study within the subject of household access to food are delineated. These are: more clear determination of the relative contribution of household access to food, to the nutritional status of women and children and, improved analysis of indicators of household access to food. PMID- 7875091 TI - Pattern of congenital heart disease in Sudanese children. AB - One hundred and seventy nine children reporting to the paediatric cardiac clinic were studied consecutively over a 2 year period (1991-1993) using medical history, physical examination, chest x-ray, electrocardiography, echocardiography and complete haemogram. 100 (56%) of them had congenital heart disease, 70(39%) had rheumatic heart disease, four had cardiomyopathy and in five children no abnormality was detected. 58 of patients with congenital heart disease were females and 42 were males. Their age ranged between two weeks and 15 years and four months. Symptoms started in infancy in 89% of 94 symptomatic patients. The commonest symptoms were breathlessness, failure to thrive, repeated chest infections and cynosis. The other six patients were detected incidentally. Almost all types of defects were represented, the commonest being ventricular septal defect (VSD), Fallot's tetralogy, pulmonary stenosis, patent ductus arteriosus, atrioventricular septal defect and secondum atrial septal defect. Five patients with VSD were preterms. 91% of patients with VSD were symptomatic. VSD was small in one-third of patients. six patients with VSD aged 5-11 years had evidence of pulmonary hypertension, one of whom had Eisenmenger with cynosis and one found inoperable because of pulmonary vascular disease. Twenty patients had extracardiac malformations in 65% of whom more than one system was involved. 53% patients were anaemic. 47% of patients were underweight and 33% were marasmic while only 14% of controls were underweight and none of them was marasmic. PMID- 7875092 TI - Antihypertensive effect of the clerodane diterpene ajugarin I on experimentally hypertensive rats. AB - Anti-hypertensive studies on ajugarin I, a representative example of a range of biologically active clerodane diterpenes was carried out. Administration of ajugarin I at 10 mg/1 in the drinking water of experimentally hypertensive rats, lowered their blood pressure from 165.00 +/- 1.57 mmHg to a normotensive level of about 116.33 +/- 1.67 mmHg in two weeks. These observations could open up new research avenues in the development of a new drug for the treatment of hypertension in humans. PMID- 7875093 TI - Drug compliance among parents and guardians of children in Accra, Ghana. AB - Through a structured questionnaire, 523 parents and guardians who received prescription to collect medicine for their wards at the pharmacy of the Department of Child Health, Korle Bu Teaching Hospital were interviewed during the months of March and April, 1993. The objectives were to determine to what extent they remembered prescription instructions for their wards and to find out any other factors that contributed to drug non-compliance. A large percentage (about 80%) were able to recount instructions given correctly. It was however worrying, that quite a sizeable number could not recount instructions given. This obviously contributed to non-compliance. Other factors that were found and which could have contributed to non-compliance were: poor economic standing, non availability of drugs at the hospital pharmacy, availability of similar drugs at home and patients getting well before the scheduled period of treatment is over. Of particular concern was the response by some parents/guardians that they would double the dosage to their wards to make up for a missed one should they forget any of the scheduled doses. Workers at pharmacy shops need to use simple practical means of giving prescription instructions, especially to illiterate patients. PMID- 7875094 TI - Hepatitis B virus infection among blood donors and pregnant women in Maiduguri, Nigeria. AB - Hepatitis due to hepatitis B virus (HBV), and sequelae such as hepatocellular carcinoma (HCC) are very common in the Maiduguri area of Nigeria. In a serological survey of 287 blood donors (all males) and 224 pregnant women, we found that 22.0% of the blood donors and 11.6% of the pregnant women were positive of HBsAg. For HBeAg the prevalence rates were 6.64% and 1.39% respectively. These findings make it imperative that all blood donations and pregnant women be screened for HBsAg. All positive blood units should be discarded and all children born to positive women be vaccinated against hepatitis B, preferably during the first year of life. In addition, a more extensive programme against hepatitis B needs to be undertaken. It is suggested that HBV vaccination be included in the expanded programme of immunization, so that all children, irrespective of the serological status of their mothers, will be vaccinated against hepatitis B. PMID- 7875095 TI - Relationship between direct agglutination test and splenic aspirate smear parasite load in visceral leishmaniasis at Baringo District, Kenya. AB - Direct agglutination test was carried out in Baringo District on 100 persons presenting with signs and symptoms suggestive of visceral leishmaniasis. Splenic aspirate smears and cultures were done on these 100 persons in order to parasitologically confirm the findings of the direct agglutination test. It was found that the direct agglutination test positively detected all 79 (79%) patients parasitologically confirmed to have visceral leishmaniasis. Irrespective of the splenic aspirate smear parasite rate, whether 1+ or 6+ on a logarithmic scale, direct agglutination test was positive. There were 21% false positives, two of whom had Schistosoma mansoni in their stools. It was not immediately known about the cause of the other false positives. It was concluded that the direct agglutination test is a good provisional serodiagnostic test for visceral leishmaniasis and should be considered for wider field application. PMID- 7875096 TI - Low bed occupancy rates in Uganda's peripheral health units: is it a policy problem? AB - A survey of 71 government and non-governmental health units ranging from hospitals to dispensaries was made to determine the utilisation of available beds in these units. In addition, an assessment of consumer practices on the use of beds was made using qualitative methods. The major finding of the study was the very low bed occupancy rates at the primary health care (PHC) level, ranging from 0.2-42%; compared to very high bed occupancy rates at the hospitals, ranging from 54-153%. Most patients referred themselves directly to the hospitals, travelling very long distances of up to 80 km. The reason for low bed occupancy rates at the primary health care level are multifactorial, including lack of medically trained personnel at this level, sporadic supply of drugs and other medical supplies and a complete breakdown in the transfer and referral system. In order to implement the policy of PHC which government has adopted, there is need to redirect resources to the PHC level and revive the referral system. PMID- 7875097 TI - Urban Schistosoma mansoni near Enyau river in Arua town, Uganda. AB - Using the Kato Katz method for quantification of parasitic eggs in faeces, 500 individuals aged between 4 and 50 years, living along River Enyau, half a kilometre from Arua town, were studied to assess the prevalence of Schistosoma mansoni in the population. The overall prevalence of Schistosoma mansoni infection was 62%. The infection was highest among school children (71.1%, i.e. 199 out of 280). Villagers who lived along the immediate vicinity of the river had a 62.8% prevalence of infection (98 out of 156). School teachers and the members of their families had the lowest infection rate (20.3% i.e. 13 out of 64). The geometric mean egg output for males and females in the community studied was 203 and 179 eggs per gram of stool, respectively. 206 (41%) out of 500 individuals had mixed infections of S. mansoni and hookworms. The rate of orally transmitted intestinal helminths like Trichuris trichiura was very low (0.8%). Ascaris lumbricoides eggs were not found. PMID- 7875098 TI - Stillbirths at Eldoret District Hospital: a retrospective study. AB - The result of a one year retrospective study on stillbirths (SBs) occurring at Eldoret District Hospital labour unit between 1st November and 31st October, 1992 is presented. The stillbirth rate (SBR) was 30.5 per 1000 births. 72.2% were fresh stillbirths (FSB). Intrapartum foetal asphyxia was the commonest probable cause of death accounting for 45.8% of all SBs while 26.4% of the SBs were unexplained. 43.9% of the SBs were low birth weight deliveries with mean gestational age for all SBs being 35.4 weeks. Spontaneous vaginal delivery was the commonest mode of delivery. 24.5% of the mothers were teenagers and 37.7% primigravidae. It is suggested that proper antenatal and intrapartum care can significantly reduce the SBR in this unit. PMID- 7875099 TI - Salt iodation in Kenya for national prophylaxis of iodine deficiency disorders. AB - This survey was conducted to monitor and evaluate the extent of salt iodation in Kenya in 1990/91. 799 salt samples were collected from 40 districts/municipalities in Kenya out of a possible 44. The samples originated from 16 different local manufacturers/packers. 35.4% of the salt samples were from a single manufacturer, and were available in all the districts/municipalities. 127 (15.9%) samples complied with the legislation of 168.5g/kg. Five samples had exceptionally high iodate--a mean of 8147.1g/kg. The mean iodate content of all samples analysed was 151 mg/kg. Uniformity of iodation was lacking as indicated by high standard deviations. Two manufacturers had iodate content complying with the minimum 168.5mg/kg required by the legislation. PMID- 7875100 TI - Recurrent polyneuropathy in pregnancy: a case report. AB - A 33-year old female patient presented with recurrent polyneuropathy during two consecutive pregnancies and recovered completely after spontaneous abortion the first time and after a normal delivery the second time. The patient has had a tubal ligation since then and has remained well up to date. PMID- 7875101 TI - Transvaginal intra-amniotic injection of methotrexate in early ectopic pregnancy. Advantages over the laparoscopic approach. AB - Methotrexate (MTX, 100 mg) was administered to 36 patients with early ectopic pregnancy locally, either under laparoscopic control into the distended fallopian tube (group A, n = 16), or transvaginally into the gestational sac directly, under ultrasound guidance (group B, n = 20). In cases with persistent beta-hCG levels (n = 7), an additional 50 mg of MTX solution was instilled into the affected tube, following transuterine tubal catheterization. Comparing the two different routes of MTX administration, it was shown that the resolution time (beta-hCG < 20 mIU/ml) in group B was significantly shorter (2.4 +/- 1.1 weeks vs. 4.1 +/- 1.9 weeks in group A, P < 0.05), with a better success rate (100% and 88%, respectively). Serum MTX levels were found within a low range and no systemic side effects were noticed. In conclusion, direct intraovular MTX injection under ultrasound guidance proved superior to the laparoscopically controlled 'blind' intratubal injection. A relatively high dose of MTX (100 mg) seems justified in order to shorten the resolution period, especially in cases with high initial beta-hCG levels and/or fetal heart motion present. PMID- 7875102 TI - Developmental outcome at 12 months corrected age for infants born less than 30 weeks gestation: influence of reduced intrauterine and postnatal growth. AB - Infants born at less than 30 weeks gestation were prospectively followed to examine the consequences of size at birth and subsequent growth on development in the first year of life. A total of 438 infants were admitted to the intensive care nursery; 53 (12.1%) infants were small for gestational age (SGA). A total of 315 infants survived to discharge; 19 (6%) were SGA. SGA infants were matched with appropriate for gestational age (AGA) infants for sex, GA, incidence of chronic lung disease and head ultrasound at discharge. The high death rate amongst SGA infants was attributable to a combination of extreme prematurity and inappropriate intrauterine growth. There was no difference between SGA and AGA groups for major developmental disability at 1-year corrected age. The effect of subsequent growth on development was examined by comparing children in the cohort above (Appropriate) and below (Small) the 10th percentile for weight at 1 year. Children small at 1 year had a significantly higher rate of major developmental disability at 1 year. Perinatal variables demonstrate that those infants small at 1 year had been of significantly younger GA, lighter BW, had received more ventilator and oxygen therapy. They also had a higher incidence of chronic lung disease. Thus, being born SGA at less than 30 weeks is not of itself associated with increased disability at 1 year when other confounding factors are taken into account. While a causal link has not been established, poor growth in the first year of life does appear to be associated with poorer outcome at 1 year, irrespective of birth status. PMID- 7875104 TI - Prenatal head position from 12-38 weeks. II. The effects of fetal orientation and placental localization. AB - The possible influence of placental localization and fetal orientation on a predominant fetal head position was studied longitudinally in 10 uncomplicated pregnancies from 12 to 38 weeks by means of real-time ultrasound. Throughout gestation, when the fetal vertebral column was oriented to the left side of the mother, head positions to the right and in midline were seen most frequently, whereas a vertebral column to the right was more often associated with a head left position and a head position in midline. These findings support the suggestion that when the fetal vertebral column is in a lateral orientation relative to the mother, one side of the fetal head is more likely to be restricted by the pelvis and backbone of the mother. However, the orientation of the fetal vertebral column does not seem to be a determining factor as the incidence of lateralized head positions increased with age, while the incidence of a vertebral column to the right or left side of the mother remained unchanged. No associations were found between the localization of the placenta and either head position or fetal lie. PMID- 7875103 TI - Prenatal head position from 12-38 weeks. I. Developmental aspects. AB - Fetal head position relative to the fetal body was studied longitudinally in 10 uncomplicated pregnancies by means of real-time ultrasound. Registrations were made at 4 weekly intervals from 12 to 36 weeks, and at 38 weeks. The percentage of assessments with optimal visualization of head position for analysis increased with age. The development of head position involved a change from a midline to a lateralized preference. It was only at 38 weeks that a clear lateralized head position was found with the head being held mainly to the right. The degree of intra- and inter-individual variability was considerable, a finding typical of motor behaviour in the healthy fetus. It is hypothesized that this bias is due to neural maturation. The implications of our findings for the subsequent development of hand preference are discussed. PMID- 7875105 TI - [Attitude of psychiatrists to electrotherapy]. AB - Psychiatrists practising in South-Eastern regions of France answered a questionnaire whose objective was to evaluate the technical conditions of the use of electroconvulsivotherapy (ECT), and to ascertain the way in which this therapy affected the lives of the patients (ECT is currently experiencing a revival in neuropsychiatric literature). Among the 400 psychiatrists who gave a complete response to the questionnaire, 22 per cent stated that they use ECT to treat inpatients. The authors try to define a typology of ECT users and non-users. The technical and scientific pragmatism of users contrasts with the highest moral reasons of non-users, although the latter do not form an homogeneous group. Factorial analysis methods were used to describe these populations with the most accuracy. The statistical analysis shows 4 sub-groups of psychiatrists: ECT users (22%); those who will never treat their patients with ECT because of ethical considerations (16%); those who will only use ECT for very serious inpatients but do not as yet have any ECT equipment at their disposal (58%); and the persons uncommitted about the use of ECT (4%). PMID- 7875106 TI - [Guidelines and practice aspects of conducting clinical trials in schizophrenia]. AB - In metropolitan France, clinical trials on human beings are governed by the law of the December 20th 1988 (Huriet's law), the purpose of which is to protect persons who are acting as subjects for clinical research. This law gives a patient freedom to choose whether or not to be part of a clinical trial and this without committing himself for the whole duration of the trial. Before the trial starts, the practitioner is obliged to explain the purpose of the experiment (its objectives, methodology, duration, limitations and risks). The principal concerns and requirements of this law are that clinical trials be based upon the most up to-date scientific knowledge, the necessity of obtaining the subject's consent, and the advice from the regional Consultative Committee for the Protection of Persons in Medical Research (CCPPRB). Any error in the application of this law may lead to prescribed penalties, both for the investigator and the programme director. This law applies to all medical disciplines and it is therefore necessary to find out how it might be applied to the specialty in question, which is psychiatry. Consent, prior to the clinical trial, presents a real ethical problem. To what degree, in fact, is acceptance of participation in a clinical trial applicable in a schizophrenic type of psychotic disorder, where the subject's symptoms hinder the legitimacy of his decision-making ability before the trial, and his evaluative judgement, from a results point of view, in the longer term? This is the heart of the ethical paradox.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875107 TI - [Viewpoint on the methodology of drug trials affecting cognition of elderly patients]. AB - Clinical trials for cognitive disorders in the elderly require specific methodological guidelines. They must take into account the psychosocial dimension of the patient and his family and must be based on serious neurobiologic knowledge. In degenerative dementias the progress of research concern genetics, molecular intercellular recognition and astrocytic cells. Biology of cognition like hippocampal long term potentiation provides good pharmacologic basis for trials. In normal brain aging several ways must be developed: aminergic systems, free radicals, excitotoxic amino-acid, nerves growth factors. Clinical trials bring informations for pharmacology and epidemiology. Cholinergic neurons are the main pharmacologic target but there are many other ones: GABA-ergic system, Tau protein, amyloid. A rigourous selection of patients allows to precise the nosology of illness responsible of cognitive disorders and to point-out early clinical signs that represent a more sensitive target. Diagnostic criteria are useful in Alzheimer's disease, memory impairment, vascular dementias and other dementias. Evaluation of stage and evolution of dementia, comorbidity, limits of age and caregiver are practical problems. The effects of drugs used to treat cognitive functions are subtle so it is necessary to detect them to choose the best tests in function of each trial. Laboratory investigations can be used to evaluate the response to drug administration. Ethical point of view is represented by the fact that old people with cognitive impairment must not be away from therapeutic progress. In this field we must consider carefully the consequences of cognitive impairment on patient judgment and consent to clinical trial. Legal problems are regulated by supranational rules and French directives of Huriet law. PMID- 7875108 TI - [Various components of smoking behavior: construction and validation of a questionnaire]. AB - The general objective of this work was to identify within the smoking population different types of smoking behavior and to determine the multiple pharmacological and psychosocial factors (and their interaction) which could determine these categories of behavior. Our first step was to construct a valid instrument consisting of a questionnaire (self-administered) with the goal to measure the different types of smoking behavior. The second step relevant to the multifactorial approach is actually in progress. Its objective is to determine the relation between the pharmacological and psychosocial factors that could explain the inter-individual differences for smoking behavior. In this paper we present the data obtained from the first step of our research. Our population is composed of 113 smokers of the age of 21 to 40 years to whom we presented a questionnaire "Types of Smoking Behavior" constructed during a preceding step. The data were submitted to different factorial analysis. Thus, a Principal Component Analysis gave us a general factor of smoking behavior or bipolar axis of high/low tobacco use (21.4% VT). The factorial analysis with varimax rotation confirmed the existence of 5 types of smoking behavior. These are "dependence" factor (29.1% VT), "regulation of negative affectivity "factor (11.2% VT), "increase of positive affect" factor (9.3% VT), "stimulation" factor (7.6% VT) and "social integration" factor (6.7% VT). These results allowed us to construct a valid questionnaire of 20 items measuring 5 types of smoking behavior. PMID- 7875109 TI - [Evaluation of the psychometric properties of the French version of the Tridimensional Personality Questionnaire (TPQ)]. AB - The Tridimensional Personality Questionnaire (TPQ) is a 100-item true-false self questionnaire proposed by R. Cloninger and based on a three independent dimensions model of personality. These three dimensions, each with four sub scales, are Novelty Seeking (NS), Harm Avoidance (HA) and Reward Dependence (RD). Recently, several groups have used the TPQ to study clinical samples, and other have reported normative data in the general population but, up to date, no result has been published on the French TPQ version. The aims of this study were therefore to assess the psychometric properties of this questionnaire and also to research an eventual relationship between dimensions of personality and anxiety and depression mood, measured by mood and anxiety scales in out-patients. A population of 165 subjects was included in this study and assessed with the TPQ. In this sample, 119 patients completed also the Hospital Anxiety and Depression (HAD) scale. The factor analysis with a Varimax rotation suggests three possible solutions with 3, 4 or 5 factors for the TPQ. These all three analysis indicate that the dimensions NS and HA load consistently unto the first two factors, and seem therefore two robust and independent dimensions. Contrastly, the RD dimension seems definitely heterogeneous, even if the RD2 sub-scale (persistence) is treated separately from the other as proposed by Cloninger. Analysis of correlations between TPQ dimensions and HAD sub-score show that only the HA dimension is related to anxiety sub-score (r = 0.34), depression subscore (r = 0.52) and total HAD score (r = 0.47).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875110 TI - [Adjustment disorders: apropos of an epidemiologic survey. Epidemiology and Psychiatry Group]. AB - An epidemiologic survey performed in France in 1990 allowed us to analyze the epidemiologic characteristics of adjustment disorders (AD). AD were defined according to the DSM III-R guidelines. AD are strongly correlated to personality disorders. The study population was young (mean age: 39 years) and predominantly female (60.3%). Marriage or life with a partner, living in the country or in small towns, liberal profession and a high level of schooling are the most significant social and demographic characteristics that emerge from this study. These patients tend to have multiple medical contacts, seeing many doctors but consuming little medication (25% of them). Comorbidity with associated personality disorders (15%) and dependency behaviors (alcohol, drugs) are frequent (9.3%), although no causative link was found between these disorders. Alcoholism may have a tendency to protect against AD. There is no seasonal factor. The patients mostly see private physicians; their geographic distribution is the inverse of the distribution of alcoholism. Numerous social and demographic risk factors for AD were found. Among the personal psychiatric history, disorders of feeding behavior and early adjustment problems were prominent. The family history often shows the existence of mental disorders in the parents. The treatment history points to a lesser consummation of psychotropic drugs, mostly limited for two classes, i.e. antidepressants (50%) and tranquilizers (40.9%), although a different pattern of behaviour was found according to the clinical types of AD. The present therapeutic approach is recent and based on psychotherapy. It differs little according to the clinical forms, with the possible exception of co-prescribed medication. This study has thus allowed us to observe the epidemiologic characteristics of AD. Adjustment disorders appear to be frequent, but their particularities do not differentiate them significantly from other types of mental disorders. PMID- 7875111 TI - [Clozapine and refractory schizophrenia. Long-term prospective study of 20 patients]. AB - Clozapine, a dibenzodiazepine derivative, has potent antipsychotic activity. But bone marrow suppression resulting in agranulocytosis has been associated with clozapine treatment; thus its clinical development has been delayed and the administration of this drug has been restricted to treatment-resistant schizophrenic patient. This report describes an open prospective study of the effects of clozapine on symptomatology of patients who are refractory to neuroleptics. Authors prospectively followed up until 36 months, 20 DSM III-R schizophrenic patients who had failed to respond to various neuroleptics (7.7 +/- 3.0). When clozapine treatment was initiated, the mean duration of the illness was 17 +/- 10 years. Various scales were used for evaluation: total BPRS, BPRS "positive symptoms", BPRS "negative symptoms", PANSS positive and PANSS negative were realized at days 0 and 15, months 1, 2 and 3 and then every 3 months. Significative improvements in total BPRS, BPRS positive symptoms and PANSS positive were noted at day 15 (p < 0.005, p < 0.026, p < 0.02, respectively); clozapine produced significant improvement on the BPRS negative symptoms and the PANSS negative at 1 month (p < 0.03 and p < 0.008, respectively). Side effects were studied: dry mouth was more prominent in the first month after wash-out (15%), while salivation was more and more prevalent (20% within the first month; 53% beyond). There was no agranulocytosis in this cohort; 2 cases (10%) of eosinophilia occurred during the first month; 20% of the patients experienced an increase in total white blood cell count (> 12.000/mm3). Weight gain (> 5 kg) affected 32% of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875112 TI - [Sequence in prescribing neuroleptics: a therapeutic alternative in refractory schizophrenia?]. AB - Although clozapine (CLZ) is effective in resistant schizophrenia, it fails in some cases leading to a therapeutic problem. Authors report a case of schizophrenia which resists several neuroleptic trials (including haloperidol, chlorpromazine and thioproperazine) and responds to a sequence of CLZ and amisulpride. These two atypical neuroleptics have the same main target (mesolimbic system) but have different and complementary affinities to neuromediator receptors: CLZ has strong serotoninergic and anticholinergic action, noradrenergic alpha 1 affinity and moderately active dopaminergic antagonism; amisulpride has a high and specific dopaminergic D2 antagonism when used at high posology. This clinical improvement can be related to "second treatment effect", described by Goldman in 1966: his study included two groups of refractory schizophrenic patients who received successively during two 6 months periods, 2 neuroleptics (fluphenazine and trifluperazine). Without initial therapeutic response, he noted a significant improvement only after change of neuroleptic medication. Tricyclic antidepressants may turn to be effective, after an initial failure, when they are given after an uneffective ECT trial. The same model may be applied and the clozapine-amisulpride sequence is proposed as an alternative treatment in resistant schizophrenia: even if CLZ is uneffective, it may produce carryover effects which ease the action of amisulpride. The hypothesis of an action on 5HT2-D2 antagonism is advanced. It leads to the general question of the opportunity of neuroleptic sequential prescription in resistant schizophrenia as a therapeutic option. PMID- 7875113 TI - [Randomized study of the therapeutic effect of electroconvulsive therapy, uni- or bilateral, on certain cognitive functions in depression, with electroencephalography monitoring. Preliminary results]. AB - Cognitive functions are known to be impaired by ECT. The aim of this study is to differentiate the effects of electroconvulsive therapy on some cognitive functions according to the mode of application of the electrodes. The brief-pulse Thymatron DG apparatus allows to control four electrical parameters and to assess electroencephalographic data. The preliminary sample comprises nine patients suffering of major depressive disorder; they are randomly assigned to the mode of application of the electrodes, bilateral or unilateral to the non dominant hemisphere. Clinical evolution is surveyed by the Montgomery and Asbert Depression Rating Scale. Non mnesic functions are assessed: arousal by CFF (Critical Fusion Frequency), and attentional, motor and decisional abilities by CRT (Choice Reaction Test). Different mnesic function are studied by selective reminding test, cued recall test, block tapping test and picture fragmentation test. After treatment by ECT, verbal mnesic functions assessed by selective reminding test are impaired with the bilateral application. Whereas they are not modified with the unilateral application. The variance of CFF regains a physiological value in the bilateral group, but remains altered in the unilateral. PMID- 7875114 TI - [Value of hydroxyzine in generalized anxiety disorder: controlled double-blind study versus placebo]. AB - A multi-centre study was designed to evaluate the efficacy of hydroxyzine in the treatment of patients presenting a generalized anxiety disorder (GAD). One hundred and thirty three patients, suffering from a GAD (according to DSM III-R criteria with 6 months duration criteria), were enrolled in a randomised, double blind, hydroxyzine (50 mg/day) versus placebo, over a 4-week trial period. By the end of the first week, the decrease of anxiety scores was significant for the hydroxyzine group, as compared to placebo (in respect of all rating criteria of anxiety). The statistical superiority for hydroxyzine continued to the end of the 4-weeks study period, and persisted at a further evaluation a week after abrupt discontinuation of active treatment. The tolerance evaluation showed that side effects were reported in 52% of hydroxyzine group versus 35% of placebo group. The most commun side effects were sleepiness (28% vs 14% with placebo), weight gain (12% vs 10%), dry mouth (14% vs 5%), loss of concentration (9% vs 8%) and insomnia (9% vs 6%). Sleepiness in the hydroxyzine group appeared during the first week and progressively disappeared later during treatment. We concluded that hydroxyzine at 50 mg/day produces a statistically and clinically significant anxiolytic effect, commencing during the first week of treatment and maintained throughout the 4-week period and after abrupt discontinuation without rebound of anxiety or withdrawal symptoms. The most commun side effect with hydroxyzine is transient sleepiness. PMID- 7875115 TI - Influence of intermittency and static components of work on heat stress. AB - This paper summarizes the results of a series of experiments established to examine the effects of the composition and pattern of physical workload on human heat tolerance and to compare the predictive abilities of a selection of prominent heat stress indices. The experiments were carried out in a climatically controlled chamber and involved mixtures of dynamic (treadmill walking) and static (weight holding) activities as appropriate. The average physiological responses to intermittent dynamic workloads did not significantly differ from those to continuous dynamic work of the same average intensity. However, the average values masked periods of peak physiological loading. The inclusion of a static load component had a negligible effect on the average level of physiological thermal strain. As a consequence, the presence or absence of a static work component did not influence the predictive abilities of the five heat stress indices examined. It was concluded that, where peak loading was unlikely to be a problem, time weighted averaging of workload was a reasonable approach in assessing industrial thermal strain and that heat stress criteria, derived originally for continuous dynamic workloads, were likely to be equally appropriate for intermittent combined workloads. However, care should be taken to ensure that peak loading did not present a health risk to industrial populations carrying out intermittent work in hot environments. PMID- 7875116 TI - Clothing, assessment and effects on thermophysiological responses of man working in humid heat. AB - This paper presents the relative importance of the different factors to be taken into account when predicting thermal exchanges when man is wearing garments while being exposed to warm environments. Factors considered are the thermal insulation of clothing (CLO), the thermal efficiency of clothing (Fcl), the clothing area factor (fcl), the pumping coefficient (p), the vapour permeation efficiency factor (Fpcl). As Fpcl depends on CLO, Fcl,fcl and p factors, physiological assessments of this factor appears to be necessary for the calculation of the maximum evaporative capacity (Emax) in clothed subjects. In this paper, comparisons of body temperatures, whole body and local sweating were made from data obtained on both unclothed and then clothed subjects working at 50 watts on a cycloergometer in warm environments (Ta = Tr = Tsk), with increasing ambient humidity levels (Pa). Results showed that clothed subjects sweated more than unclothed man for the same Pa increases and hidromeiosis occurring on the skin of unclothed man seemed to be responsible for this. Sweat accumulation in the clothes confirms that the decrease in the evaporative sweat efficiency for clothed subjects was closely associated with the threshold for occurrence of core temperature drift. However the less important slope in the Tcore vs delta Pa relationship for clothed subjects compared to that for unclothed implies a more efficient body cooling thanks to clothing, which does not lead to as great a physiological disadvantage as expected. Pumping effect and additional concurrent evaporation could account for this phenomenon: the ISO model (Required sweat rate) which includes an additional air velocity as a function of metabolism allows us to consider this beneficial influence of increased Emax in clothed subjects. However this effect should not be considered when the model is used for unclothed subjects. PMID- 7875117 TI - Task performance in heat: a review. AB - A wide array of variable conditions, tasks, subject populations, etc., have been included in studies that have produced data on perceptual motor performance in the heat. This paper uses a methodology for comparing these studies, regardless of the inherent differences, which allows determination of whether thermal effects are dominant enough to persist through diverse combinations of variables. Approximately 160 individual studies of perceptual motor performance reported in the literature were summarized based on thermal level, duration of exposure and the type of task performed. Results indicated no dominant effect of duration of exposure to the heat and no dominant effect of thermal level on mental/cognitive tasks. For perceptual motor tasks other than very simple or mental tasks, an onset of performance decrement was noted in the 30-33 degrees C WBGT range of temperature. This temperature level is consistent with the Recommended Exposure Limits for work in the heat at low levels of metabolic heat. PMID- 7875118 TI - Protective clothing and heat stress. AB - The high level of protection required by protective clothing (PPC) severely impedes heat exchange by sweat evaporation. As a result work associated with wearing PPC, particularly in hot environments, implies considerable physiological strain and may render workers exhausted in a short time. Current methods of describing evaporative heat exchange with PPC are insufficient, will overestimate evaporative heat loss and should not be recommended. More reliable measures of the resistance to evaporative heat transfer by PPC should be developed and standardized. Direct measurements of evaporative resistance of PPC may be carried. However, a more promising method appears to be the definition of evaporative resistance on the basis of the icl-index for the fabric layers. The icl-index is a permeation efficiency ratio, which in combination with clothing insulation determines the evaporative heat transfer. Current methods should be further developed to account for effects of moisture condensation and microclimate ventilation. PMID- 7875119 TI - Climatic stress in coalmining in Germany: occupational health aspects. AB - Coalmining in Germany is performed in depths as low as 1400 m. Owing to an average thermal gradient of 30 m/K the work underground is burdened by heat stress to which occupational medicine must pay special attention. Therefore heat stress standards and mining safety regulations have been set up not only for coal production but also for mine rescue activities. This specific situation of heat burdened work in the coal mining industry in Germany is discussed under the specific aspects of German coalmining regulations (Klima-Bergverordnung und Plan fur das Grubenrettungswesen). PMID- 7875120 TI - International heat stress standards: a review. AB - Heat stress indices are included in international standards to provide methods and limits for the design, assessment and control of hot thermal environments. Indices used in standards are described with particular reference to those in ISO standards concerned with the ergonomics of the thermal environment. ISO 7243 provides a simple method for assessing and controlling hot environments based upon the WBGT (web bulb globe temperature) index. ISO 7933 describes an analytical method of assessment of hot environments based upon the human heat balance equation and the calculation of the required sweat rate index (Sreq). This standard is discussed in detail with particular consideration of its use in practical application. The method has been evaluated in both laboratory and industrial contexts. Limitations of the standards and areas where further development is required, are presented. PMID- 7875121 TI - Transgenic germ cell mutation assays: a small collaborative study. PMID- 7875122 TI - Excision repair and gene orientation modulate the strand specificity of UV mutagenesis in a plasmid-borne yeast tRNA gene. AB - Ultraviolet (UV) mutagenesis in a plasmid-borne Saccharomyces cerevisiae tRNA gene (SUP4-o) occurs preferentially at sites where the pyrimidine in the base pair is part of a dipyrimidine sequence on the transcribed strand. In this study, we examined whether excision repair, or strand identity with respect to DNA replication, influences this strand bias. The specificity of UV mutagenesis was determined for a wild type (RAD) strain and an isogenic excision repair-deficient (rad1) derivative, each carrying SUP4-o on the vector YCpMP2, or another vector (YCpJA1) that differed only in the orientation of SUP4-o with respect to a unique origin of replication. Most (> or = 90%) of the SUP4-o mutations induced by UV in these strains were single base pair substitutions, predominantly (> 87%) transitions. The rad1 defect and inversion of SUP4-o in the RAD strain eliminated the strand preference, whereas inversion of SUP4-o in the rad1 strain caused it to reappear. Both conditions also altered the distribution of frequently mutated sites and the relative fraction of transitions at TT sequences. These results suggest that excision repair and gene orientation can be important determinants for the strand and site specificities of UV mutagenesis in SUP4-o on YCpMP2 and YCpJA1. We consider several possible explanations for our observations, including potential roles for transcription by RNA polymerase II, sequence context effects on the efficiency of excision repair, and inherent differences in strand mutability or translesion synthesis by the leading and lagging strand DNA replication complexes. PMID- 7875123 TI - Effects of X-irradiation on mouse testicular cells and sperm chromatin structure. AB - The testicular regions of male mice were exposed to x-ray doses ranging from 0 to 400 rads. Forty days after exposure the mice were killed and the testes and cauda epididymal sperm removed surgically. Flow cytometric measurements of acridine orange stained testicular samples indicated a repopulation of testicular cell types following x-ray killing of stem cells. Cauda epididymal sperm were analyzed by the sperm chromatin structure assay (SCSA), a flow cytometric measurement of the susceptibility of the sperm nuclear DNA to in situ acid denaturation. The SCSA detected increased susceptibility to DNA denaturation in situ after 12.5 rads of x-ray exposure, with significant increases following 25 rads. Abnormal sperm head morphology was not significantly increased until the testes were exposed to 60 rads of x-rays. These data suggest that the SCSA is currently the most sensitive, non-invasive method of detecting x-ray damage to testicular stem spermatogonia. PMID- 7875124 TI - Improved prediction of carcinogenic potencies from mutagenic potencies for chemicals positive in rodents and the Ames test. AB - Most studies of correlation between logs of mutagenic potency (MP) and cancer potency (CP) have obtained relatively small but statistically significant estimates of correlation (r) and corresponding log-log slope (b, in Log[CP] = a + b Log[MP]). But for mutagenic carcinogens, multistage cancer theory predicts that b and r should be highest when MP values best estimate mutation yields per unit dose at concentrations at least as high as those observed to cause cancer in bioassay animals. To test this hypothesis, the correlation of Ames test and rodent cancer potencies was examined for a total number n of 134 chemicals reported as positive in both assays. Values of maximum significant cancer potency (CP, in [mmol/kg-day]-1) were obtained from a published carcinogenic potency database. Values of maximum mutagenic potency (MP, as revertants per mmol/L plate) were estimated from 2,347 sets of Ames test data reported by the NTP mutagenicity testing program, supplemented by similar data newly obtained for ten heterocyclic amines. For compounds with one or more significantly positive MP estimates based on approximately linear Ames test dose-response data, linear regression of maximum values of Log(CP) on Log(MP) yielded b = 0.27 +/- 0.065 and r = 0.39 (P = 0.0001, n = 105), similar to previously reported results for relatively large n. As predicted, when MP values were additionally restricted to include only values estimated from Ames test data approximately linear at corresponding lowest-TD50 concentrations, similar regressions yielded significantly improved fits (e.g,. b and r approximately 0.6, P < 10(-7), n = 68). Implications of these findings are discussed concerning the quantitative role that mutations like those measured in the Ames test may have in explaining observed cancer-bioassay results. PMID- 7875125 TI - Preferential effects of the chemotherapeutic DNA crosslinking agent mitomycin C on inducible gene expression in vivo. AB - The immediate effects of a single dose of the chemotherapeutic DNA crosslinking agent, mitomycin C (MMC), on the expression of several constitutive and drug inducible genes were examined in a simple in vivo system, the 14 day chick embryo. We observed no effect of MMC on the steady-state mRNA expression of the constitutively expressed beta-actin, transferrin, or albumin genes. In contrast, MMC treatment significantly altered both the basal and drug-inducible mRNA expression of two glutethimide-inducible genes, 5-aminolevulinic acid (ALA) synthase and cytochrome P450 CYP2H1. The basal expression of these genes was transiently but significantly increased over a 24 hr period following a single dose of MMC. Conversely, MMC significantly suppressed the glutethimide-inducible expression of these genes when administered 1 to 24 hr prior to the inducing drug. The effects of MMC on both basal and drug-inducible ALA synthase and CYP2H1 mRNA expression were principally a result of changes in the transcription rates of these genes. In contrast, MMC treatment had little or no effect on glutethimide-induced expression of ALA synthase or CYP2H1 when administered 1 hr after the inducing drug, suggesting that a very early event in the induction process represents the target for these MMC effects. Covalent binding studies demonstrated that the effects of MMC on gene expression were closely correlated temporally with formation of [3H]-porfiromycin-DNA adducts. These results support the hypothesis that genotoxic chemicals specifically target their effects to inducible genes in vivo. PMID- 7875126 TI - Metabolic activation of carcinogenic aromatic amines by fish exposed to environmental pollutants. AB - Activation of arylamines to mutagenic metabolites by hepatic S9 fractions has been evaluated as a biomaker of fish exposure to pollutants, using gilthead seabream (Sparus aurata), a valuable fish species from the Spanish South Atlantic littoral, as model organism. To obtain maximal sensitivity to the mutagenic action of aromatic amines, a strain of Salmonella typhimurium overproducing O acetyltransferase was used. Fish were treated with Aroclor 1254, pesticides (malathion and dieldrin), or copper(II), and compared to Aroclor 1254-treated rats. The promutagen activation capabilities of the S9 fractions were further characterized by studying the effect of two monooxygenase inhibitors, alpha naphthoflavone, a well known inhibitor of aromatic hydrocarbon-inducible forms of cytochrome P450, and methimazole, a substrate for the flavin monooxygenase (FMO) system. This study shows that 2-aminoanthracene (2-AA) and 2-acetylaminofluorene (AAF) activation by gilthead liver is enhanced by treatment of fish with different xenobiotics. The catalyst responsible for this enhanced activation appears to be different for each promutagen and, at least for 2-AA, dependent on the type of xenobiotic. The data presented indicate further that treatment of gilthead with some compounds, such as malathion and dieldrin, enhances the activation of aromatic amines in liver, without inducing ethoxyresorufin-O deethylase activity. The use of acetyltransferase-overproducing bacteria appears to be a useful tool in the study of arylamine activation by fish liver, where biotransformation capability is lower than in mammals. PMID- 7875127 TI - Metabolic reduction of novel 3,4-dichloro-5-nitrofurans in Salmonella typhimurium. AB - To gain insight on biochemical mechanisms of mutagenesis and carcinogenesis by the experimental carcinogens, 5-nitrofurans, a new series of 3,4-dichloro-5 nitrofurans, comprised of 3,4-dichloro-5-nitro-2-acetylfuran (I), 3,4-dichloro-5 nitro-2-bromoacetylfuran (II), methyl 3,4-dichloro-5-nitro-2-furoate (III), were synthesized and tested for their activation to mutagenic forms in the standard plate assay using Salmonella typhimurium TA98, TA100, and TA100NR, a derivative of TA100 deficient in nitroreductase activity. The mutagenic responses in TA98 were 2- to 6-fold lower compared to TA100. Furthermore, I and II were less active in TA100NR, while compound III was about four times more mutagenic in TA100NR compared to the parent strain TA100. Incubation of III with NADPH and bacterial lysates showed that the extent of reduction was greater in TA100 compared to TA100NR. High-pressure liquid chromatography analysis of the ethyl acetate extract obtained from incubation of III with lysates of TA100 revealed the formation of four metabolites with retention times of about 4.0, 5.7, 10.0, and 14.3 minutes. The spectroscopic and chromatographic properties of the components with retention times of 10.0 and 14.3 minutes were identical to two derivatives obtained by chemical reduction of III, and thus represent nitroreduction products. These derivatives have been identified as cis- and trans-oxime isomers of methyl 3,4-dichloro-2-furoate, based on spectroscopic analyses. These oximes were not mutagenic for TA100. Furthermore, III was more mutagenic under anaerobic conditions, suggesting that secondary superoxide or nitroanion free radicals generated from nitroreduction are not responsible for the mutagenicity of III. In addition, the higher mutagenic response in TA100NR, and the lack of mutagenic activities of the amino and the oxime analogs of III suggest that the mutagenic activation of III might be due to the nitroso intermediate or involve mechanisms other than nitroreduction. PMID- 7875128 TI - Relative genotoxic activities of pesticides evaluated by a modified SOS microplate assay. AB - The genotoxic activities of 47 pesticides were determined using a modified SOS microplate assay in which the induction of beta-galactosidase in E. coli PQ37 was used as a quantitative measure of genotoxic activity. The results were compared with those obtained with anethole, curcumin, and capsaicin, a few examples of naturally occurring compounds present in foods. The assays were conducted with pesticides dissolved either in a suitable solvent, such as 10% DMSO in physiological saline or dispersed in sodium taurocholate micelles, to simulate conditions in the small intestine from where these substances are normally absorbed from the diet. 4-Nitroquinoline oxide (4-NQO) served as the reference standard of a direct acting mutagen. In micellar form, 4-NQO and 25 of the 47 pesticides tested showed significantly higher genotoxic activities than when they were tested in an organic solvent. In micellar form the SOS inducing potency of 4 NQO was almost twice as high as in 10% DMSO in physiological saline. In taurocholate micelles, the five most active compounds had activities in the range of 1,234-3,765 units/mumol and in the order of decreasing activities they were ranked as follows: malathion > dichlorvos > lindane > chlordane > endrin. They were significantly less active than 4-NQO (less than 40%). In micellar solution the naturally occurring compounds, anethole, curcumin, and capsaicin gave activities of 4,594, 928, and 809 units/mumol, respectively. These studies show that genotoxicity may depend upon the environment in which cells are exposed to these potential genotoxins. It appears that testing of the more hydrophobic compounds, both synthetic and naturally occurring, are needed. PMID- 7875129 TI - Frameshift mutations in Salmonella induced by the extracts of medicinal herbs Lannea edulis (Sond.) Engl. and Monotes glaber Sprague. AB - Lannea edulis and Monotes glaber have been prescribed for various affectations in the traditional medical practice of Zimbabwe and other parts of Africa. Mutagenicity testing using Salmonella typhimurium strains TA97a, TA98, and TA100, indicated that the aqueous extracts of these plants induced frameshift mutations in Salmonella. The extract of L. edulis displayed marginal mutagenicity in strain TA97a while that of M. glaber showed a significant dose-dependent mutagenicity in both strains TA97a and TA98. There was no mutagenic effect observed in strain TA100. Two other plant extracts, those of Lannea discolor and Dolichos kilimandscharicus, were nonmutagenic in all three strains. PMID- 7875130 TI - Adrenaline stimulated cyclic adenosine monophosphate response in leucocytes is reduced after prolonged physical activity combined with sleep and energy deprivation. AB - The mechanism for adrenergic desensitisation during physical stress was studied by measuring [125I] cyanopindolol ([125I]CYP) binding sites and the adrenaline stimulated cyclic adenosine monophosphate (cAMP) responses in peripheral blood leucocytes from ten male cadets during a 5-day military training course. The cadets had physical activities around the clock corresponding to a daily energy consumption of about 40,000 kJ but with an intake of only 2,000 kJ, and only 1-3 h of sleep in the 5 days. During the course, the maximal cAMP response to adrenaline stimulation was reduced to about 45% in granulocytes and to 52% in mononuclear cells, and the half maximal response was obtained only at 5-10 times higher adrenaline concentrations than in the control experiment. The binding sites for [125I]-CYP in mononuclear cells increased during the course. However, [125I]-CYP measured not only surface receptors but also intracellular receptors and might even have represented other binding sites. In conclusion, this study showed that decreased cAMP response to adrenergic stimulation would seem to be one of the mechanisms behind adrenergic desensitisation during stress. PMID- 7875131 TI - Moment and power generation during maximal knee extensions performed at low and high speeds. AB - In the present study a method was developed to determine knee joint moment and power generated at low to very high velocities of knee extension. A group of 21 male subjects performed maximal knee extensions at four levels of external loading provided by a flywheel system. Knee extension was performed with no restrictions on joint angular velocity and acceleration. An interpolation procedure was employed to obtain moment and power at standard velocities. During each single knee extension peak velocity, peak moment, peak power and moment and power at 50 degrees knee flexion were determined (0 degree = full extension). While maximal recorded angular velocity averaged 693 degrees.s-1 (range 479 1030), maximal recorded moment and power were 226 N.m (157-278) and 1140 W (573 1688), respectively, which were generated at velocities of 55 degrees.s-1 (12 148) and 523 degrees.s-1 (327-846). Isokinetic moment and power were obtained for comparison. The velocity range applied was larger using the flywheel method (21 1030 degrees.s-1 individual range) than that achieved isokinetically (30-240 degrees.s-1). Significant differences were observed between flywheel and isokinetic measurements. These discrepancies may be ascribed to differences in the time course of muscle length change and contractile force generation imposed by the two measuring methods. However, by the nonisokinetic measuring method presently employed, knee extension moment and power could be determined from low to very high angular extension velocity, at loading and contraction conditions comparable to those encountered during sport and exercise. PMID- 7875132 TI - Effects of different strength training regimes on moment and power generation during dynamic knee extensions. AB - This study examined the effect of different training regimes on moment and power generation during maximal knee extensions at low to very high extension velocities (0-1000 degrees.s-1 individual range). A group of 24 soccer players performed 12 weeks of progressively adjusted strength training of the knee extensors at either high resistance (HR, n = 7), low resistance (LR, n = 6), loaded kicking movements (FU, n = 6), while one group served as controls (n = 5). Moment and power generation of the knee extensors were determined before and after the training period with a nonisokinetic measuring method recently described. Following HR training, knee extension moment increased 9%-10% at knee angular velocities 0 (isometric) and 30 degrees.s-1 (P < 0.05), peak moment increased 20% at 240-300 degrees.s-1 (P < 0.05), while power generation increased 5%-29% at 240-480 degrees.s-1 (P < 0.01). In addition, in the HR group maximal recorded power increased 45% (P < 0.01). After FU training a 7%-13% increase in moment and power was observed at 30-180 degrees.s-1 (P < 0.05). Following LR training, peak moment increased 9% at 120 degrees.s-1 (P < 0.05). Improvements in knee extension moment and power were generally related to the angular velocities employed during training. However, as evaluated using the present measuring method, moment and power increased not only at very low but also at high knee angular velocities following the high-resistance strength training. PMID- 7875133 TI - Increased capillary density due to atrophy of ischaemic soleus muscle of the rat. AB - This investigation was undertaken to determine whether a severe limitation of blood supply by external iliac artery ligation can change the number and density of capillaries in rat soleus muscle. The external iliac artery in one hindlimb was ligated for 2, 7 or 28 days, and the other, sham-operated, hindlimb was used as a control. Muscle blood flow in the ischaemic soleus muscle at 2, 7 and 28 days after external iliac artery ligation was significantly decreased compared with the control. The muscle fibre area and the ratio of the fibre area to body mass in the ischaemic soleus muscle at 28 days after the external iliac artery ligation were significantly reduced in the ischaemic soleus muscle, but no change in the number of capillaries per fibre was observed. Capillary density per millimetres squared at 28 days and the ratios of the number of capillaries around type I fibres to the fibre area at 7 and 28 days were significantly increased in the ischaemic soleus muscle (P < 0.05). These results suggested that long-term severe limitation of blood flow in the soleus muscle by ligation of the external iliac artery could have induced the increase in capillary density, as a result of atrophy of muscle fibres rather than capillary growth. PMID- 7875134 TI - Oxidative stress induced by intermittent exposure at a simulated altitude of 4000 m decreases mitochondrial superoxide dismutase content in soleus muscle of rats. AB - The effects were examined of 6-month intermittent hypobaric (4000 m) exposure on the antioxidant enzyme systems in soleus and tibialis muscles of rats. At the end of the 6-month experimental exposure, the six rats in both the exposed group and the control group were sacrificed. Immunoreactive mitochondrial superoxide dismutase (Mn-SOD) contents were measured as well as the activities of antioxidant enzymes [Mn-SOD, cytosolic SOD (Cu,Zn-SOD), catalase (CAT), and glutathione peroxidase (GPX)]. Thiobarbituric acid-reactive substances (TBARS) were also determined as an indicator of lipid peroxidation. The high altitude exposure resulted in a marked increase in TBARS content in soleus muscle, suggesting increased levels of oxygen free radicals. Conversely, significant decreases in both Mn-SOD content and activity in soleus muscle were noted after exposure. Such trends were not noticed in tibialis muscle. On the other hand, no significant changes in Cu,Zn-SOD, CAT, or GPX were observed in either muscle. These results suggested that the increases in lipid peroxidation were most probably a result of decreased Mn-SOD function which was more depressed in oxidative than in glycolytic muscle. PMID- 7875136 TI - Hyperventilation-induced changes of blood cell counts depend on hypocapnia. AB - Voluntary hyperventilation for 20 min causes haemoconcentration and an increase of white blood cell and thrombocyte numbers. In this study, we investigated whether these changes depend on the changes of blood gases or on the muscle work of breathing. A group of 12 healthy medical students breathed 36 l.min-1 of air, or air with 5% CO2 for a period of 20 min. The partial pressure of CO2 decreased by 21.4 mmHg (2.85 kPa; P < 0.001) with air and by 4.1 mmHg (0.55 kPa; P < 0.005) with CO2 enriched air. This was accompanied by haemoconcentration of 8.9% with air (P < 0.01) and of 1.6% with CO2 enriched air (P < 0.05), an increase in the lymphocyte count of 42% with air (P < 0.001) and no change with CO2 enriched air, and an increase of the platelet number of 8.4% with air (P < 0.01) and no change with CO2 enriched air. The number of neutrophil granulocytes did not change during the experiments, but 75 min after deep breathing of air, band-formed neutrophils had increased by 82% (P < 0.025), whereas they were unchanged 75 min after the experiment with CO2 enriched air. Adrenaline and noradrenaline increased by 360% and 151% during the experiment with air, but remained unchanged with CO2 enriched air. It was concluded that the changes in the white blood cell and platelet counts and of the plasma catecholamine concentrations during and after voluntary hyperventilation for 20 min were consequences of marked hypocapnic alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875135 TI - Left ventricular performance during prolonged exercise and early recovery in healthy subjects. AB - The effect of semi-supine long lasting exercise to exhaustion [61 (SD 10) min] on left ventricular systolic performance was studied by echocardiography in 16 young healthy volunteers. During the incremental phase of exercise, the ejection fraction increased from 65.2 (SD 4.1)% to 80.1 (SD 4.8)% (P < 0.0001), then it levelled off up to the end of exercise [81.7 (SD 4.4)%, P < 0.0001 vs rest]. During recovery, the ejection fraction rapidly and steadily decreased to a value similar to that at rest [66.1 (SD 5.0)%, n.s.). A similar pattern was shown by the systolic blood pressure/end-systolic volume coefficient, which rose from 3.2 (SD 0.8) mmHg.ml-1 to 7.5 (SD 2.7) mmHg.ml-1 (P < 0.0001) in the initial phase and subsequently did not change until the end of exercise [7.0 (SD 2.2) mmHg.ml 1, P < 0.0001 vs rest], to fall sharply after the cessation of exercise [2.9 (SD 1.1) mmHg.ml-1 at the 10th min, n.s. vs rest]. Exercise and recovery indices of left ventricular performance were not correlated with exercise duration, maximal heart rate and increase in free fatty acids. The present results indicated that, after the initial increase, left ventricular performance remained elevated during prolonged high intensity exercise and that conclusions on exercise cardiac performance drawn from postexercise data can be misleading. PMID- 7875138 TI - Effects of posture, hypotension and locally applied vasoconstriction on the middle ear microcirculation in anaesthetized humans. AB - Studies by laser-Doppler flowmetry of middle ear microcirculation changes induced by physical and chemical stimuli in the animal have only recently been made. This prospective study, performed in humans, was designed to compare the effects of a postural manoeuvre (headup tilt 30 degrees), hypotension and locally applied vasoconstriction on middle ear blood flow during anaesthesia. Circulatory changes provoked by a headup tilt of 30 degrees, and successive intravenous boluses of potent vasodilators, were compared with circulatory changes provoked by locally applied adrenaline, in ten healthy patients in good physical states undergoing middle ear surgical repair. Heart rate and direct arterial pressure were continuously recorded via a radial artery cannula. Middle ear blood flow was continuously recorded via a laser-Doppler probe placed on the promontorium cavi tympani. Metabolic parameters (partial pressure of O2 and CO2 in arterial blood, pH, arterial lactate concentrations) and arterial concentrations of propofol were measured just before and just after the experiment. Headup tilt did not modify heart rate, mean arterial pressure or middle ear blood flow. Vasodilators (nicardipine, nitroprusside, nitroglycerin) provoked a fall in arterial pressure (P < 0.0001, P < 0.0001, P < 0.019, respectively), but did not induce any significant variations in heart rate; variations occurred in middle ear blood flow (P > 0.05, not significant) which were different according to patients and agents. Locally applied adrenaline provoked a fall in the middle ear blood flow (P < 0.0012), with no effect on heart rate and arterial pressure. There were no significant changes in metabolic values, or propofol serum concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875137 TI - Changes in magnetic resonance images in human skeletal muscle after eccentric exercise. AB - To investigate the time-course of changes in transverse relaxation time (T2) and cross-sectional area (CSA) of the quadriceps muscle after a single session of eccentric exercise, magnetic resonance imaging was performed on six healthy male volunteers before and at 0, 7, 15, 20, 30 and 60 min and 12, 24, 36, 48, 72 and 168 h after exercise. Although there was almost no muscle soreness immediately after exercise, it started to increase 1 day after, peaking 1-2 days after the exercise (P < 0.01). Immediately after exercise, T2 increased significantly in the rectus femoris, vastus lateralis and intermedius muscles (P < 0.05) and decreased quickly continuing until 60 min after exercise. At and after the 12th h, a significant increase was perceived again in the T2 values of the vastus lateralis and intermedius muscles (P < 0.01) [maximum 9.3 (SEM 2.8)% and 10.9 (SEM 2.2)%, respectively]. The maximal values were exhibited at 24-36 h after exercise. In contrast, the rectus femoris muscle showed no delayed-stage increase. Also, in CSA, an increase after 12 h was observed in addition to the one immediately after exercise in the vastus lateralis, intermedius and medialis and quadriceps muscles as a whole (P < 0.01), reaching the maximal values at 12 24 h after exercise. The plasma creatine kinase activity remained unchanged up to 24 h after and then increased significantly 48 h after exercise (P < 0.05). Beginning 12 h after exercise, the subjects whose T2 and CSA increased less than the others displayed a faster decrease in muscle soreness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875139 TI - The effects of exercise duration on dynamics of respiratory gas exchange, ventilation, and heart rate. AB - This study investigated the effect of exercise duration on the response dynamics of oxygen consumption (VO2), carbon dioxide output (VCO2), ventilation VE), and cardiac frequency (fc) following stepped changes in exercise intensity, by manipulating the duration of the pretransition exercise period. A group of 11 healthy men performed a stepped exercise intensity cycling protocol on three separate occasions, each consisting of a stepped increase from 55% to 65% peak oxygen consumption (VO2,peak) of 6-min duration, followed by a stepped decrease to 55% VO2,peak of 10-min duration. This stepped protocol was preceded by either 5, 15, or 60 min of cycling at 55% VO2,peak. The response times for each variable were calculated at 10% increments between the prestep baselines and poststep plateaux. Following the stepped increase, the response times for VO2 at the 50%, 60%, 70%, 80%, and 90% relative increments were significantly reduced in the 60 min condition compared to the 15-min condition (P < 0.05); however, the response times for VCO2, VE, and fc were not significantly altered across the three conditions. No significant differences were found in the response times for VO2, VCO2, VE, and fc, across the three conditions following the stepped decrease in exercise intensity. It was concluded that the faster response time of aerobic metabolism to a stepped increase in exercise intensity was mediated by increases in active muscle temperature, leading to improved oxygen utilisation. PMID- 7875140 TI - Effect of growth on efficiency and fatigue in extensor digitorum longus muscle of the rat. AB - The effect of growth on work output, energy consumption and efficiency during repetitive dynamic contractions was determined using extensor digitorum longus muscles of 40-, 60-, 120- and 700-day-old male Wistar rats. When work output of each contraction was normalized to the work output of the first contraction it was found that work output initially increased over the first 10-20 contractions by approximately 8% in each age group. Thereafter a faster decrease in work output was found in the youngest group (approximately 2% each contraction) compared to the older groups (approximately 0.7% each contraction). After 40 contractions the reduction in work output was significantly different only between the youngest group and the two oldest groups (-30% vs -5%). These differences in fatigue were not associated with differences in adenosine 5' triphosphate and phosphocreatine concentrations or in lactate production. Total work output and high-energy phosphate consumption increased by approximately 555% and 380% from age 40 to 120 days, respectively. Consequently, efficiency was significantly higher (approximately 32%) in the older groups compared to 40-day old animals. Normalized for muscle mass, mean rate of high-energy phosphate consumption was similar in all groups whereas mean power output was significantly lower in the youngest group (approximately 46%). Thus, the difference in efficiency between the young and the other groups may be attributed to a lower external power production in the youngest group rather than changes in energy turnover. PMID- 7875141 TI - Critical power test for ramp exercise. AB - The critical power test for cycle ergometry has been criticised as providing an overestimate of the real value of the critical power. Part of the blame may rest in the practical problem associated with getting reliable measurements of longer endurance times when power settings are not much above the critical power. However, by adjusting the incremental slope of ramp exercises, exhaustion brought about by high power and in a reasonably short time can be ensured, so avoiding this practical problem. This communication presents the theory and methods required to obtain estimates of both anaerobic work capacity and critical power from several ramp tests conducted to exhaustion. The method is illustrated with published laboratory data collected from exercising subjects. PMID- 7875142 TI - The effect of prolonged isometric contractions on muscle fluid balance. AB - Ultrasound scanning was performed at three sites above the fossa supraspinata on nine healthy subjects and five patients with myofascial shoulder pain. This method produced a well-defined depiction of the soft tissue layers above the fossa supraspinata and reproducible muscle thickness measurements. In the healthy subjects the average distance from the skin surface to the trapezius muscle was 7.7 mm and the average thickness of the trapezius muscle was 5.3 mm, and the average thickness of supraspinatus muscle was 20.0 mm. The supraspinatus muscle was thinner at the medial measuring site than at the other two sites. In contrast, a tendency towards a larger distance was seen from the skin to trapezius muscle at the medial measuring site than at the other two sites. No statistical differences were found between the two groups of subjects either at rest or during brief shoulder abductions. All the subjects performed a 30 degrees unilateral isometric shoulder abduction test to exhaustion. The median endurance time was 33 min for the healthy subjects and only 5 min for the patients. The ratings of perceived exertion (RPE) were in line with this, since the increment in RPE with time was larger for the patients than for the healthy group. The reduced shoulder abduction endurance time in the patient group may have been related to impaired muscle function and/or pain development. During the 33-min shoulder abduction in the healthy subjects, the thickness of supraspinatus muscle increased by 14%, indicating muscle swelling, whereas the thickness of trapezius muscle remained constant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875143 TI - Statistical evidence consistent with two lactate turnpoints during ramp exercise. AB - A number of studies have identified the existence of two ventilation thresholds during ramp or incremental exercise to exhaustion on the cycle ergometer. This study was undertaken to investigate whether two threshold turnpoints could be identified in blood lactate concentration data collected at such times. Five trained athletes provided serial blood samples on several occasions each during a 3-month period of training. Blood lactate concentration was analysed by fitting models with no, one or two turnpoints. Ordinary residuals from the first two models were often found to exhibit an oscillatory behaviour consistent with the existence of two turnpoints in lactate concentration. A comparative analysis of goodness of fit of these models revealed that the model with two turnpoints was significantly better than either of the simpler models. This suggests that two transitions exist, which divide the time domain for blood lactate concentration in ramp exercise into three regions. These two transitions may correspond to the two ventilation thresholds. PMID- 7875144 TI - Skeletal muscle mechanics in osteoporotic and nonosteoporotic postmenopausal women. AB - The purpose of this study was to evaluate single-joint, dynamic muscle function of osteoporotic (OST) and nonosteoporotic (N-OST) women. Knee flexor and extensor function in postmenopausal women (6th decade OST, n = 15; 7th decade OST, n = 10; 6th decade N-OST, n = 6; 7th decade N-OST, n = 5) were evaluated at five angular velocities from 60 degrees.s-1 to 300 degrees.s-1. All subject groups had similar anthropometric measurements, but the 6th decade N-OST group were more physically active than the age-matched OST group. The OST and N-OST women produced peak torque at similar knee angles. The 6th decade N-OST women produced significantly greater knee extensor mean peak torque and angle specific torque, and mean work than any of the other three groups (P < 0.05). However, knee flexor function was equivalent throughout the groups for most comparisons, except those between the 6th decade N-OST and 7th decade OST. While previous research has shown an early loss of flexor muscle function in aging women, our data indicated that women with osteoporosis also experience a deterioration in quadriceps muscle function not encountered within the N-OST subjects. It is possible that such a change is precipitated by reduced physical activity, and may mirror deterioration in bone mineral content. PMID- 7875145 TI - Pulmonary function of a firemen-diver population: a longitudinal study. AB - Non smoking, male professional firemen-divers (n = 20) underwent two pulmonary function tests (PFT) separated by 8-9 years. Measured data were compared to European Coal Steel Community recommended reference values to permit cross sectional and then longitudinal studies. Higher vital capacity (VC) and forced expiratory volume in 1 s (FEV1; both P < 0.001), and lower residual volume (P < 0.01) were observed in both PFT. Longitudinal analysis showed a smaller VC reduction than FEV1 reduction, leading to a FEV1/VC percentage decrease with time. Maximal mid expiratory flow (MMEF) and MMEF/VC changes during this 9-year period showed an unusually pronounced decrease, suggesting possible chronic effects of diving on small airways. Thus, it is suggested from our observations that a hyperbaric stimulus compensates in part for the effects of aging on VC and that obstructive disease could occur in subjects with long diving experience. PMID- 7875146 TI - The effect of posture change on blood volume, serum potassium and whole body electrical impedance. AB - After standing for 1 h, ten subjects (7 male, 3 female) assumed a supine position for a further hour. Whole body bioelectrical impedance increased progressively during the hour spent in the supine position: after 60 min supine the increase was 13(6 to 32) omega. Blood and plasma volumes, estimated from haematocrit and haemoglobin concentration, increased by 8.0(6.7 to 12.4)% and 16.7(12.3 to 20.8)% (median(range)) respectively after 60 min supine. Serum potassium concentration had fallen after 10 min supine (4.1(0.1)mmol l-1; mean (SEM)) relative to the standing value (4.6(0.1)mmol l-1) and was unchanged thereafter. Serum osmolality (P = 0.991) and sodium (P = 1.000) and chloride (P = 0.998) concentrations remained unchanged throughout the study. The fall in serum potassium concentration in the supine position does not appear to be a simple dilutional effect consequent upon increases in blood and plasma volume as there was no effect of postural change on serum sodium or chloride concentrations. PMID- 7875147 TI - Role of granulocyte-macrophage colony-stimulating factor as adjuvant treatment in neutropenic patients with bacterial and fungal infection. AB - The results are presented of two preliminary studies conducted to assess the role of GM-CSF as adjuvant treatment in neutropenic patients with bacterial or fungal infections. In the first study the effect of GM-CSF on the rate of response to antibiotics was assessed. Febrile neutropenic patients (n = 91) were randomized to receive ticarcillin-clavulanate plus netilmicin with or without GM-CSF (60 micrograms/m2). Response rates were significantly higher in patients who received antibiotics plus GM-CSF (p = 0.05). An increase in neutrophil count was seen in 89% of GM-CSF patients with initial low neutrophil counts (< 100/microliters) compared with 67% of control patients (p = 0.04). In the second study the activity of GM-CSF in patients with fungal infections was assessed. Neutropenic patients with documented fungal infections received amphotericin B plus GM-CSF. Of the eight evaluable patients, six responded and four had a complete response to treatment. The neutrophil counts of the two non-responding patients did not increase substantially during GM-CSF treatment and both died of their fungal infection. The prognosis of neutropenic patients with fungal infections is usually poor and the results of this pilot study are therefore very encouraging. The two studies show that GM-CSF is able to stimulate neutrophil recovery in neutropenic patients and may improve the response to antibiotic and antifungal treatment. PMID- 7875148 TI - Granulocyte-macrophage colony-stimulating factor in combination with pentavalent antimony for the treatment of visceral Leishmaniasis. AB - The efficacy of GM-CSF was investigated in 20 neutropenic patients (< 1500 neutrophils/microliters) with acute visceral leishmaniasis due to Leishmania chagasi. Patients were randomized to receive either GM-CSF, 5 micrograms/kg daily (intravenously or subcutaneously), or placebo for ten days, in combination with pentavalent antimony, 10-20 mg/kg daily for 20 days. Neutrophil counts were significantly greater on days 5 and 10 of treatment in the GM-CSF group compared with the placebo group (p < 0.02). Eosinophil and monocyte counts were also significantly increased in the GM-CSF group at day 10 (p < or = 0.03). Interestingly, at day 30, platelet counts were significantly increased in the GM CSF group on days 5 and 10 (p = 0.04 and 0.02, respectively). Patients in the GM CSF group experienced fewer secondary bacterial or viral infections than placebo patients. Infections occurred in only three patients given GM-CSF compared with eight patients given placebo (p < 0.04). All patients had complete resolution of disease symptoms at three months. Few adverse events were recorded. GM-CSF given subcutaneously at a dose of 5 micrograms/kg daily for ten days was well tolerated, reversed neutropenia rapidly and reduced the number of secondary infections in patients with leishmaniasis. PMID- 7875149 TI - Potential role of cytokines in disseminated mycobacterial infections. AB - Organisms belonging to the Mycobacterium avium complex (MAC) are common pathogens in immunosuppressed and AIDS patients. This paper reviews the role of cytokines in the pathogenesis of MAC infection. MAC organisms mainly infect monocytes and macrophages, and the effect of HIV infection on susceptibility of macrophages to MAC infection is largely unknown. Both GM-CSF and tumour necrosis factor-alpha can induce mycobacteriostatic/mycobactericidal activity in MAC-infected macrophages. The activity of interferon-gamma on mycobacterial infection appears to be dependent on the type of macrophage: in murine peritoneal and human monocyte-derived macrophages, interferon-gamma does not inhibit the intracellular growth of MAC, whereas in intestinal macrophages interferon-gamma results in inhibition of MAC. Transforming growth factor-beta 1, interleukin-10 and interleukin-6 have all been shown to counteract the immunoactivating cytokines and MAC survival may be due to induction of these inhibitory cytokines within the macrophage. GM-CSF has been given to patients with disseminated MAC infection. Isolated macrophages from these patients demonstrated increased superoxide anion production and enhanced mycobacteriostatic/cidal activity compared with macrophages isolated from the same patients before GM-CSF treatment. These results suggest that GM-CSF may have potential in the treatment of MAC infection. PMID- 7875150 TI - Growth factors and the molecular control of haematopoiesis. AB - In the absence of appropriate growth factors, for example interleukin-3 or GM CSF, cultured bone marrow stem cells die by a process known as apoptosis or programmed cell death. Apoptosis may occur in vivo when concentrations of specific growth factors are limiting and may be a means of regulating cell numbers. Growth factors are also essential for proliferation of bone marrow stem cells but differentiation can occur, provided there is a survival stimulus in the absence of growth factors. Combinations of growth factors may be synergistic in stimulating the survival and proliferation of multipotent stem cells. Although neither stem cell factor, nor GM-CSF alone can significantly induce the proliferation of stem cells, the combination induces the proliferation of these cells. Committed progenitor cells such as granulocyte-macrophage colony-forming cells, however, are stimulated to proliferate by GM-CSF alone, while stem cell factor in combination with GM-CSF results in only a slight additive effect. To date, most research has concentrated on the growth stimulatory factors. GM-CSF has an important role in the reversal of chemotherapy-induced myelosuppression in cancer patients and in other bone marrow disorders. A number of growth inhibitory molecules have now been identified, such as macrophage inhibitory protein-1 alpha. In the future, it is possible that improvements in cure rates may be achieved in cancer patients by combining the growth inhibitory factors with the stimulatory factors. Inhibitory factors may be given before chemotherapy to prevent toxicity and stimulatory factors may be given afterwards to treat neutropenic patients. PMID- 7875151 TI - Combination of ganciclovir and granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. The ACTG 073 Team. AB - The efficacy and safety of a combination of ganciclovir plus GM-CSF was evaluated in AIDS patients with cytomegalovirus retinitis. In phase A, patients were randomized to receive ganciclovir, 5 mg/kg every 12 h for 14 days followed by 5 mg/kg daily, with (n = 24) or without (n = 29) GM-CSF (1-8 micrograms/kg daily subcutaneously) to maintain absolute neutrophil counts between 2500 and 5000 cells/microliters. In phase B, after 16 weeks zidovudine was added to the regimen of 16 patients receiving ganciclovir plus GM-CSF and 20 receiving ganciclovir alone. At this stage, GM-CSF was added to the treatment protocol of any patient receiving ganciclovir plus zidovudine who became neutropenic. In phase A, patients in the ganciclovir plus GM-CSF group had significantly higher neutrophil counts than ganciclovir-alone patients (p = 0.0001). Overall, 12.5% of patients treated with GM-CSF developed neutropenia (absolute neutrophil counts < 500/microliters phase A and < 750/microliters phase B) compared with 45% of patients treated without GM-CSF. GM-CSF patients missed 10 of a possible 4705 scheduled doses of ganciclovir compared with 34 missed doses of a possible 6584 in the ganciclovir-alone group (p = 0.011). There was a trend, although not statistically significant, for patients in the GM-CSF group to experience delayed progression of their retinitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875152 TI - Effects of granulocyte-macrophage colony-stimulating factor on wound contraction. AB - The effect of topical recombinant murine and human GM-CSF, 1 or 10 micrograms/cm2 for one to ten days, on the contraction and healing of acute and chronic granulating wounds infected with Escherichia coli was studied in Sprague-Dawley rats. Bacterial contamination of wounds produced significant inhibition of wound contraction. Application of GM-CSF at either dose level to infected wounds markedly increased the rate of wound closure compared to the rate in infected untreated controls. Ten days treatment was found to be more effective than a single application. An advanced stage of wound healing was observed at ten days in the GM-CSF-treated rats compared with controls. Bacterial counts decreased in the GM-CSF-treated wounds which may suggest bactericidal activity. Topical treatment with GM-CSF was shown to effectively inhibit the retardation of wound closure produced by bacterial contamination and may therefore be useful in the management of patients with infected wounds. PMID- 7875153 TI - Potential role of granulocyte-macrophage colony-stimulating factor as vaccine adjuvant. AB - The uses of GM-CSF as an immunomodulator and vaccine adjuvant are reviewed. GM CSF has a variety of effects on immune responses: it induces class II major histocompatibility complex antigen expression on the surface of macrophages; it enhances dendritic cell maturation and migration; it results in a localized inflammation at the injection site; and it has marked effects on maturation of haematopoietic progenitor cells in the bone marrow. Animal and human studies suggest that administration of GM-CSF can increase antibody titres to foreign antigens. Monkeys injected with human interleukin (IL)-3 plus GM-CSF, at a different injection site, developed peak antibody titres which were 8- to 30-fold higher than those in monkeys injected with IL-3 alone. In a study of ovarian cancer patients receiving GM-CSF to prevent chemotherapy-induced neutropenia, two patients who had demonstrated a low titre of antithyroid antibodies prior to the study showed an increase in antibody titre and transient thyroiditis after administration of GM-CSF. Recently a GM-CSF/antigen fusion protein has been tested. An antibody corresponding to a specific idiotype expressed on B-cell lymphomas was fused to GM-CSF and injected into mice with B-cell lymphoma xenografts. The mice developed antibodies to the lymphoma and there was a protective effect against disease progression. Preliminary results of clinical trials using GM-CSF in humans suggest that it enhances antibody responses to hepatitis B vaccine. On the basis of these preliminary results, several clinical trials are being planned and it would appear that GM-CSF has potential as a vaccine adjuvant. PMID- 7875154 TI - Prediction of the role of granulocyte-macrophage colony-stimulating factor in animals and man from in vitro results. AB - The possibility of predicting the clinical effects of cytokines from in vitro data is discussed, using GM-CSF as an example. GM-CSF incubated with bone marrow cells has been shown to induce proliferation and colony formation, predominantly of the colony-forming unit granulocyte and granulocyte-macrophage types. Daily treatment of normal monkeys with GM-CSF resulted in transient neutropenia followed by neutrophilia. After withdrawal of GM-CSF the neutrophil levels returned to baseline. Predictably, GM-CSF administration results in accelerated neutrophil recovery in patients with chemotherapy-induced neutropenia. GM-CSF has also been shown to induce microbial killing by neutrophils and monocytes in vitro. This activity translated into a dose-related protection of GM-CSF pretreated mice infected with lethal doses of micro-organisms. Interleukin-3 (IL 3) increases the cellularity of the bone marrow and GM-CSF can induce mobilization of bone marrow cells into the peripheral blood. Therefore, it was predicted and subsequently proved that a combination of these cytokines is synergistic, increasing the yields of peripheral blood progenitor cells which could be collected and then retransplanted into patients undergoing myeloablative chemotherapy. Monkeys injected with recombinant human IL-3 and GM-CSF had increased antibody titres to human IL-3 compared with monkeys given IL-3 alone, suggesting a potential use of GM-CSF which was not predicted from its in vitro results, that of vaccine adjuvancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875155 TI - Dose escalation combination carboplatin/cyclophosphamide chemotherapy for epithelial ovarian cancer. AB - Dose intensification chemotherapy is currently under investigation in ovarian cancer. In order to establish an optimum dose for future colony stimulating factor trials, 16 patients with ovarian cancer were treated with dose-escalation combination carboplatin plus cyclophosphamide chemotherapy without growth factors. The initial carboplatin dose, 300 mg/m2, was increased to a maximum dose of 400 mg/m2. The initial cyclophosphamide dose, 600 mg/m2, was increased to a maximum dose of 1200 mg/m2. Of 10 patients completing 6 cycles, six patients (60%) were escalated to carboplatin 400 mg/m2 and cyclophosphamide 600-1200 mg/m2. Myelosuppression was severe, with all 6 patients requiring platelet and/or packed red blood cell transfusions. Based on these results, carboplatin 400 mg/m2 with cyclophosphamide 600 mg/m2 was selected as the starting dose with hematopoietic growth factors. PMID- 7875156 TI - Intramural adenocarcinoma of the uterus, arisen from adenomyosis uteri, showing unique histologic appearances. Report of two cases. AB - Two cases of uterine adenocarcinoma which grew mainly in myometrium and showed unique histologic appearances are reported. Both cases were considered to have arisen from adenomyosis uteri because transitional figures were observed between carcinoma cells and adenmyotic glands in one case, and carcinomatous glands were scattered in myometrium and were associated with endometrial stroma which mimicked benign adenomyosis in another. The former case was poorly differentiated adenocarcinoma and the latter was well-differentiated adenocarcinoma. Interestingly, in the latter case, the carcinoma cells were transformed into papillary adenocarcinoma such as has been observed in the thyroid gland, and formed well-demarcated nodular mass. These findings indicate that adenocarcinoma which arise from adenomyosis uteri could show various histologic appearances, in addition to usual endometrioid adenocarcinoma. PMID- 7875157 TI - Breast cancer and prognostic factors. Tumour size, degree of differentiation, proliferation kinetics and expression of steroid hormone receptors. AB - In a group of 161 patients with operable cancer of the breast, tumour size, axillary node status and histopathological grading were correlated. Furthermore, steroid hormone receptor status was assessed both biochemically and immunohistochemically. The rate of Ki67-positive cells, the ploidy status and the S-phase fraction of the carcinoma, as assessed by means of flow-cytometry, were measured and correlated with tumour size and conventional histopathological grading. As expected, a significant correlation between tumour size and the frequency of axillary lymph node metastases was found (p < 0.00001). There was however, also a significant increase of undifferentiated cancers with increasing tumour size (p < 0.001). There was no correlation between steroid hormone receptor expression and grading but a slight decrease of immunohistochemically oestrogen receptor positive cancers with increasing tumour size (p < 0.02). On the other hand, there was a marked increase of both Ki67-score (p < 0.003) and S phase fraction (p < 0.001) with increasing tumour size. Neither of the first two parameters correlated significantly with grading. The frequency of aneuploid tumours was dependent on tumour size (p < 0.05) as well as grading (p < 0.01). The findings point towards a change of biological properties of the cancer during the course of growth, such as histopathological dedifferentiation and increased proliferation fraction and frequency of aneuploid tumours. The expression of steroid hormone receptors however is virtually unchanged. PMID- 7875158 TI - Intraperitoneal chemotherapy with carboplatin and recombinant interferon alpha in ovarian cancer. AB - Twenty-five patients with Stage III ovarian cancer were entered into a trial with intraperitoneal combinations of carboplatin (400 mg/cqm) and recombinant interferon alfa (50 MU). All patients had received prior intravenous platinum based chemotherapy and underwent 2nd look laparotomy at study entry. Our study indicates that this combination chemotherapy is safely administered by the intraperitoneal route. Myelotoxicity was frequent, but rarely of grade 3. No major local toxicity was recorded by accessing the peritoneal cavity with a temporary catheter. The response to treatment was promising in the group of patients with less then 2 cm residual disease at study entry (15 patients); in this group, all patients had no clinical evidence of disease at the completion of the therapy. In 2 cases reexploration was performed and pCR was recorded. Only one patient of this group relapsed during a mean follow-up of 21 months. Two pCRS were also recorded in the group of patients with more than 2 cm at 2nd look (9 patients), although relapse occurred after 9 and 15 months respectively. In the remaining patients of this group, persistence of disease was observed after intraperitoneal chemotherapy. PMID- 7875159 TI - Pelvic lymphocysts after radical hysterectomy and lymphadenectomy. AB - Five cases (5.5%) of lymphocysts were diagnosed and treated, among 80 type III modified radical hysterectomies performed for cervical cancer St. Ia2-IIa, in the last 6 years. Identification was initially made by palpation and confirmed by CT or US, in 4/5 cases in the first 2 postoperative months. Pelvic pain, fever and pressure symptoms were the most common clinical findings. A conservative approach was successful in 4/5 cases. Spontaneous regression was observed in one, while needle aspiration under radiologic guidance with (1/3) or without (2/3) tube insertion was applied in the rest. Conservative treatment failed in the last case presenting with a 12 cm cyst. An intestinal fistula developed, necessitating partial resection of the ileus and marsipulization. The complicated course of this patient's disease may indicate that a more aggressive treatment is warranted for large persisting cysts located in the irradiated field. PMID- 7875160 TI - Endometrial carcinoma in breast cancer patients treated with tamoxifen. Two case report and review of the literature. AB - Recent reports suggest an increased incidence of endometrial cancer in breast cancer patients under long-term adjuvant tamoxifen (TAM) treatment. The Authors describe two cases of endometrial adenocarcinoma among 80 post-menopausal patients affected with breast cancer and treated with TAM. PMID- 7875161 TI - Extraperitoneal staging lymphadenectomy for locally advanced cervical cancer. Effective, cost-effective and minimally invasive. AB - Twenty-three patients locally advanced cervical cancer Stage IIB-IV underwent extraperitoneal staging pelvic and para-aortic node sampling via a single incision. All surgeries were completed in under one hour and most patients discharged within 2 days. The method of staging is a minimally invasive technique with minimal morbidity that requires only brief hospitalization and allows rapid resection of even bulky disease without disruption of peritoneal surfaces or increased risk of radiation-related enteric complications. PMID- 7875162 TI - Diagnostic histologic criteria of atypical adenomatous hyperplasia and well differentiated adenocarcinoma of the endometrium. AB - The purpose of the study was to evaluate certain histological features of adenomatous hyperplasia diagnosed in endometrial curretings, that will enable us to distinguish atypical glandular hyperplasia from early well-differentiated adenocarcinoma. The material for this study was composed of 519 endometrial hyperplasias diagnosed in curettings. Of these, 244 were adenomatous hyperplasias, 109 were cystic hyperplasias, 93 mixed types and 73 were atypical hyperplasias. The cases of atypical hyperplasia were subsequently operated on, and among them, 26 proved to be adenocarcinomas. All histological sections of the currettings showing the atypical hyperplasia were re-evaluated to find criteria diagnostic of adenocarcinoma. The authors have considered as diagnostic criteria the stroma infiltration, the mitotic activity, the nuclear atypia, the stratification of nuclei and the presence of necrosis. The stroma infiltration seems to be the most important indication of an adenocarcinoma of the endometrium. PMID- 7875163 TI - Octreotide scintigraphy for small cell lung carcinoma: past, present or future? PMID- 7875164 TI - A hybrid method of attenuation correction for positron emission tomography brain studies. AB - A hybrid method for attenuation correction (HAC) in positron emission tomography (PET) brain studies is proposed. The technique requires the acquisition of two short (1 min) transmission scans immediately before or after the emission study, with the patient and the head fixation system in place and after removing the patient from the scanner with the head fixation system alone. The method combines a uniform map of attenuation coefficients for the patient's head with measured attenuation coefficients for the head fixation system to generate a hybrid attenuation map. The HAC method was calibrated on 30 PET cerebral studies for comparison with the conventional measured attenuation correction method by ROI analysis. Average differences of less than 3% were found for cortical and subcortical regions. The HAC technique is particularly suitable in a PET clinical environment, allowing a reduction of the total study time, greater comfort for patients and an increase in patient throughput. PMID- 7875165 TI - Principal component analysis of dynamic positron emission tomography images. AB - Multivariate image analysis can be used to analyse multivariate medical images. The purpose could be to visualize or classify structures in the image. One common multivariate image analysis technique which can be used for visualization purposes is principal component analysis (PCA). The present work concerns visualization of organs and structures with different kinetics in a dynamic sequence utilizing PCA. When applying PCA on positron emission tomography (PET) images, the result is initially not satisfactory. It is illustrated that one major explanation for the behaviour of PCA when applied to PET images is that it is a data-driven technique which cannot separate signals from high noise levels. With a better understanding of the PCA, gained with a strategy of examining the image data set, the transformations, and the results using visualization tools, a surprisingly easily understood methodology can be derived. The proposed methodology can enhance clinically interesting information in a dynamic PET imaging sequence in the first few principal component images and thus should be able to aid in the identification of structures for further analysis. PMID- 7875166 TI - In vivo metabolic studies of the trans-(R,R) isomer of radioiodinated IQNP: a new ligand with high affinity for the M1 muscarinic-cholinergic receptor. AB - E-(R,R)-IQNP is a new ligand analogue of IQNB, which has high affinity for the cholinergic-muscarinic receptor. Earlier studies have demonstrated high cerebral uptake of activity with selective localization in M1 receptor subtype areas of the brain. In this paper we describe the results of metabolic studies of E-(R,R) IQNP directed at determining the metabolic fate of this ligand and the identification of the radioactive species observed in the brain and heart tissue. Tissue Folch extracts demonstrated that the lipid-soluble extracts from brain contained 87.0% +/- 1.65% of the activity up to 24 h. In the heart, 61.9% +/- 7.50% of the activity was extracted in the lipid-soluble extract after 30 min, decreasing to 51.4% +/- 0.65% by 4 h. In contrast, data from other tissues studied demonstrated large amounts of either aqueous soluble activity or activity which was not extracted from the tissue pellet material; analysis of lipid organic extracts revealed the following results: liver (4 h), 7.43% +/- 0.96%; serum (4 h), 3.73% +/- 0.87%; urine (24 h), 9.4%; feces (24 h), 16.5%. Thin-layer chromatographic (TLC) and high-performance liquid chromatographic (HPLC) analyses of lipid-soluble brain extracts indicated that only unmetabolized E-(R,R)-IQNP was detected (99.4% +/- 1.25%). Activity which was extracted into the organic phase from heart tissue was also determined by TLC and HPLC analysis to contain large amounts of unmetabolized ligand after 4 h (88.5% +/- 0.57%). In addition, however, low levels of two additional radioactive components were detected which increased with time. TLC analysis of the plasma lipid extracts indicated only a small amount of unmetabolized E-(R,R)-IQNP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875167 TI - Three-dimensional realignment of activation brain single-photon emission tomographic studies. AB - Two methods for 3D realignment of activation brain single-photon emission tomographic (SPET) studies are analyzed. The first is based on principal axes transformation (PAT). The second uses the results of the first method as initial values to start a least-squares iterative process (LS) to search for the maximum value of the correlation function. Both methods were tested with simulated and real studies. The results of the PAT method showed a maximum translation error of 0.3 +/- 0.1 pixels and a rotational error of 1.2 +/- 0.7 degrees in a total of 100 runs. For the LS method these errors were 0.2 +/- 0.1 and 0.6 +/- 0.3. The realignment for 34 real studies was assessed by three expert observers. The alignment was found to be satisfactory in all cases for the LS method, and in 18 cases (53%) for the PAT method. From the results we conclude that a combination of both methods allows the accurate realignment of SPET neuroactivation studies. PMID- 7875168 TI - Artificial neural networks that use single-photon emission tomography to identify patients with probable Alzheimer's disease. AB - Single-photon emission tomographic (SPET) images using technetium-99m labelled hexamethyl-propylene amine oxime were obtained from 97 patients diagnosed as having Alzheimer's disease, as well as from a comparison group of 64 normal subjects. Multiple linear regression was used to predict subject type (Alzheimer's vs comparison) using scintillation counts from 14 different brain regions as predictors. These results were disappointing: the regression equation accounted for only 33.5% of the variance between subjects. However, the same data were also used to train parallel distributed processing (PDP) networks of different sizes to classify subjects. In general, the PDP networks accounted for substantially more (up to 95%) of the variance in the data, and in many instances were able to distinguish perfectly between the two subjects. These results suggest two conclusions. First, SPET images do provide sufficient information to distinguish patients with Alzheimer's disease from a normal comparison group. Second, to access this diagnostic information, it appears that one must take advantage of the ability of PDP networks to detect higher-order nonlinear relationships among the predictor variables. PMID- 7875169 TI - Ambulatory monitoring of left ventricular function in patients with Parkinson's disease and postural hypotension. AB - Left ventricular (LV) function was continuously monitored using a radionuclide detector (VEST) after intravenous injection of 25 mCi technetium-99m labelled red blood cells in nine patients with Parkinson's disease and postural hypotension (group 1) and ten patients with Parkinson's disease but without postural hypotension (group 2). LV function and blood pressure were monitored in the supine position for 15 min (period A), upon changing posture from the supine to the upright position for 10 min (period B), and upon returning to the supine position for 10 min (period C). In group 1, the passage from period A to period B induced a significant decrease in end-diastolic volume, end-systolic volume and ejection fraction (all P < 0.01). In group 2, ejection fraction increased (P < 0.05) upon changing posture from the supine to the upright position. Ejection fraction (F = 33, P < 0.01), end-diastolic volume (F = 9, P < 0.05) and end systolic volume (F = 10, P < 0.05) were significantly different between the two groups. In group 1, stroke volume, cardiac output and vascular peripheral resistance decreased from period A to period B (all P < 0.001). In group 2, no changes in stroke volume, cardiac output and vascular peripheral resistance were observed from period A to period B. All parameters were similar in the two groups during the periods A and C. Upon changing posture from the supine to the upright position, patients with Parkinson's disease and postural hypotension showed marked changes in parameters of LV function induced by vascular abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875170 TI - Indium-111 pentetreotide in the diagnostic work-up of patients with bronchogenic carcinoma. AB - In a prospective study we examined 38 patients with primary bronchogenic carcinoma to validate the use of indium-111 pentetreotide (IPT) as a diagnostic tool. Of these 38 patients, 25 had small cell lung cancer (SCLC) and 13, non small cell lung cancer (NSCLC). The aim of the study was to investigate whether (a) the disease can be reliably detected, (b) IPT allows differentiation between SCLC and NSCLC and (c) IPT provides further information on metastatic disease. After giving their informed consent the patients were injected and imaged 4 and 24 h later using a planar whole-body technique. In addition single-photon emission tomography of the thorax and, if necessary, other areas of the body was performed at 24 h. In the 25 patients with SCLC 22 sites of primary tumour were correctly identified (true-positive, TP); one was false-negative (FN) and two were true-negative (TN), the patients being in full remission. Metastases were correctly identified in ten instances (lung, bone and brain), while the findings were FN in five cases. An additional six FN findings resulted in the area of the upper abdomen due to the physiological uptake in the liver, spleen and kidneys. In the 13 patients with NSCLC, ten findings were TP and 3 FN with respect to the primary tumour. Two FNs were squamous cell carcinoma, and one, adenocarcinoma. Metastases were TP in nine cases and FN in one.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875172 TI - Effect of renal maturation on the clearance of technetium-99m mercaptoacetyltriglycine. AB - To investigate the effect of growth and maturation on the global kidney clearance of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3), we investigated 509 children who attended for 99mTc-MAG3 renography in our department. In order to estimate the normal maturation of the kidney, only children who were classified as "normal" using diagnostic criteria were included in this study (n = 109). Kidney clearance was calculated using a gamma camera technique and a 20-min blood sample. There was a progressive increase in the clearance of 99mTc-MAG3 throughout childhood and into adolescence (mean clearance value below 2 month was 31.4 ml/min, mean clearance value above 12 years was 287 ml/min). When clearance was normalised to body surface area (BSA) a different pattern was seen, with a progressive increase from 3 weeks of age (mean value < 0.2 years: 208 ml/min/1.73 m2) to a plateau at the end of the first year of life (mean value > 2 years: 303 ml/min/1.73 m2). Maturation of the kidney as defined by the normalised clearance of 99mTc-MAG3 is therefore complete by the end of the 1st year of life, after which any change in non-corrected clearance values may be attributed to growth. To investigate the appropriate normalisation factor for 99mTc-MAG3 clearance in children, clearance values were compared to height, weight and BSA. The relationships were described using a linear model; the correlation coefficients demonstrated that BSA has the highest strength of relationship with 99mTc-MAG3 clearance. Body surface area may be used over 1 year of age to normalise the clearance values of 99mTc-MAG3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875171 TI - Technetium-99m sestamibi scintigraphy for the assessment of lower extremity ischaemia in peripheral arterial disease. AB - Technetium-99m sestamibi was used for functional investigation of the muscle perfusion of lower extremities in 35 patients with peripheral vascular disease. The aim was to test what useful information could be obtained by additional imaging of the legs in patients referred for risk stratification with dipyridamole myocardial scanning. Posterior images were acquired over the thighs and calves after postocclusive reactive hyperaemia and at rest. Inter- and intraextremity ratios and differences between the stress and rest data were used for the assessment of abnormal circulation. Arteriography was performed in every case, and surgical procedures or transluminal angioplasty in 31 patients. To estimate diagnostic accuracy, the results of 99mTc-sestamibi scintigraphy were compared with those of angiography and the functional consequences of revascularization procedures. The sensitivity and specificity of 99mTc-sestamibi scintigraphy were 55% and 25%, respectively, with an overall accuracy of 50%. Apparently methodological error was not responsible for these poor results. Instead, a paradoxically high uptake of the radiopharmaceutical in muscles supplied by significantly stenosed vessels was identified as the main source of both false-negative and false-positive results. The phenomenon resembles the findings of a previous study involving delayed administration of thallium-201 after exercise. In conclusion, 99mTc-sestamibi scintigraphy has not proved sufficiently reliable to help in the management strategy for patients with peripheral vascular disease. PMID- 7875173 TI - An evaluation of iodine-123 iodoazomycinarabinoside as a marker of localized tissue hypoxia in patients with diabetes mellitus. AB - Peripheral vascular disease is a serious and common complication in patients with diabetes mellitus (DM). Evaluation is, conventionally, by transcutaneous oxygen tension measurements (TcpO2), although this technique has some limitations in the evaluation of tissue viability. We have evaluated a new, radiolabelled, in vivo marker of tissue hypoxia, iodoazomycinarabinoside (IAZA), by comparing TcpO2 measurements with patterns of iodine-123 IAZA uptake in ten patients (19 lower limbs) with DM and peripheral vascular disease using conventional gamma camera imaging techniques. Normal uptake patterns were seen in limbs in which normal TcpO2 measurements were obtained. Diffusely increased uptake of [123I]IAZA was seen in limbs with reduced TcpO2. Focally increased uptake was seen in ulcers or in areas of atrophic skin change. A semi-quantitative measure showed an inverse correlation between [123I]IAZA and TcpO2 values. These data suggest that tissue hypoxia can be imaged in this population of patients and that severity of disease can be assessed. A longitudinal prospective trial is now being developed. PMID- 7875174 TI - Radionuclide targeting and dosimetry at the microscopic level: the role of microautoradiography. AB - The understanding of localisation mechanisms and microdosimetry of diagnostic and therapeutic radiopharmaceuticals depends on knowledge of their biodistribution at the microscopic level (cellular and subcellular) in the target tissues. Various methods have been advanced for obtaining information about this microdistribution: subcellular fractionation, secondary ion mass spectrometry imaging, microprobe elemental analysis in the electron microscope, and microautoradiography. This review compares these approaches, and discusses in detail the methodology of microautoradiography (the most generally useful approach) with imaging and therapy radionuclides. Literature examples of applications of microautoradiography in nuclear medicine are reviewed, and the future potential contribution of the techniques is assessed. PMID- 7875175 TI - Sensitivity versus specificity in melanoma imaging using iodine-123 iodobenzamide and indium-111 pentetreotide [1]. PMID- 7875176 TI - Cushing's syndrome due to a black adenoma of the adrenal gland: lack of tumour visualization by radiocholesterol scintigraphy. PMID- 7875177 TI - Nuclear medicine and other radiologic imaging techniques: competitors or collaborators? AB - In summary, there will continue to be competition between scintigraphy and the various other modalities used in Radiology, with Nuclear Medicine having to periodically reconfirm its value as current methods are refined and newer techniques are introduced. Compared to the revolutionary changes in radiologic imaging which have occurred over the past two decades. Nuclear Medicine and radiopharmaceutical technology have advanced at a slower, more evolutionary pace. It is essential that the nuclear medicine profession continue to provide solid data to demonstrate the validity and utility of radionuclide imaging results. We must be prepared to demonstrate to an often skeptical medical public that the "shinier" new methods in Radiology do not necessarily hold all the advantages when it comes to diagnostic evaluation of patients. There are many situations where the Nuclear Medicine procedure remains the most cost-effective and appropriate test for a particular patient evaluation, and those of us working in this field must not be shy about informing our clinical colleagues when our method has a demonstrated advantage over a competing imaging modality. PMID- 7875178 TI - Spontaneous reporting of adverse drug reactions to non-steroidal anti inflammatory drugs. A report from the Spanish System of Pharmacovigilance, including an early analysis of topical and enteric-coated formulations. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are the third most commonly prescribed group of drugs in Spain. We present here the profile of adverse drug reactions (ADRs) attributed to them and reported to the Spanish System of Pharmacovigilance (SSPV) between 1983 and 1991, together with a preliminary analysis of topical, slow-release (SR) and enteric-coated (EC) preparations. Out of 18,348 reports of ADRs included in the SSPV database, 1609 (8.8%) implicated an NSAID. NSAIDs ranked second after antibiotics (15.1% of all reports) among the most commonly implicated drugs. Half of the patients were more than 55 years old, and 60% were women. Diclofenac (364 reports), piroxicam (282), indomethacin (197), naproxen (155), and ketoprofen (137) were the most commonly implicated NSAIDs in reports of ADRs. The most commonly reported ADRs were gastrointestinal (39%), cutaneous (20%), and those affecting the central and peripheral nervous system (9%). Seven reactions had a fatal outcome, and 138 were considered life threatening. Forty-nine reports included previously undescribed ADRs. There were 98 reports describing ADRs attributed to topical NSAIDs; 5 of these described 11 general reactions, such as duodenal ulcer, gastrointestinal bleeding, diarrhoea, dyspnoea, facial oedema, aggravation of bronchospasm, and angioedema. One hundred and sixty-eight reports referred to SR and EC preparations. The ratio of gastrointestinal to non-gastrointestinal reactions to SR-EC diclofenac was higher in the case of SR-EC diclofenac than in the case of plain diclofenac (P = 0.037); similarly, the ratio of CNS to non-CNS reactions to SR-EC indomethacin was also higher than the corresponding ratio with plain indomethacin (P = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875179 TI - Adverse reactions attributed to sumatriptan. A postmarketing study in general practice. AB - There are several reports on cardiac adverse reactions attributed to the antimigraine drug sumatriptan in the recent literature. In order to assess the frequency and the character of adverse reactions to sumatriptan, a postmarketing cohort study was performed one year after registration of the drug in The Netherlands. With assistance of 86% of the drug dispensing general practitioners in The Netherlands, 1727 patients who had received sumatriptan were traced in July, 1992. Via their general practitioners, a questionnaire about use of sumatriptan, adverse reactions and other medication was sent to the patients in December 1992. During the study period, seven patients were lost to follow-up. Of the 1720 remaining patients, 1202 (70%) responded to the questionnaire, of whom 1187 had actually used sumatriptan. The most frequently reported suspected adverse reactions were paraesthesiae (139 patients, 95% CI 9.9%-13.5%) and dizziness (96 patients, 95% CI 6.5%-9.7%). Chest pain after use of sumatriptan was reported by 94 patients (7.9%, 95% CI 6.4%-9.4%), and according to the close temporal relationship with the intake of sumatriptan and a positive rechallenge, a causal relationship was probable in most of those patients. The frequency of chest pain attributed to sumatriptan was higher in females (9.0% vs 4.6%; relative risk 1.9, 95% CI 1.1-3.4). Age and hypertension were not associated with chest pain attributed to sumatriptan. Dyspnoea attributed to sumatriptan was reported by 26 patients (2.2%), and was associated with obstructive lung disease (relative risk 5.4 95% CI 1.7-16.9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875180 TI - Metoprolol alpha-hydroxylation is a poor probe for debrizoquine oxidation (CYP2D6) polymorphism in Jordanians. AB - The frequency distribution of the 8-h urinary ratio of log metoprolol/alpha hydroxymetoprolol was assessed in 65 healthy, unrelated Jordanian volunteers. There was no apparent bimodality in the frequency distribution of this ratio among the subjects studied. The frequency of the poor metabolizer phenotype of metoprolol alpha-hydroxylation was 1.5% (one subject). There was a significant correlation (r = 0.61, P < 0.05, n = 39) between the log metoprolol/alpha hydroxymetoprolol and the log debrisoquine/4-hydroxydebrisoquine ratios. However, the frequency of poor metabolizer status of debrisoquine among the 39 subjects was 7.7% (three subjects). Only one of the poor metabolizer of metoprolol alpha hydroxylation. These findings indicate that metoprolol alpha-hydroxylation by CYP2D6 represents a poor probe for studying debrisoquine polymorphism in Jordanians. PMID- 7875181 TI - Interindividual variability of coumarin 7-hydroxylation in a Turkish population. AB - One hundred healthy Turkish volunteers (70 male, 30 female) aged from 19 to 56 years were given 5 mg coumarin p.o. after an overnight fast. Urine samples were collected before and 2, 4 and 8 h after drug administration. The extent and rate of formation of 7-OH-coumarin (7OHC) was determined by the urinary excretion of the metabolite as measured with the fluorometric method. On average, 80% of 7OHC formed was excreted in 2 h. The total amount of 7OHC formed was 59.8% (21.5%) (mean and SD, n = 100, range 17-100%) of the given dose. The percentage of 7OHC excreted during the first 2 h compared with the 7OHC excretion at 8 h was a constant and stable individual characteristic for the rate of the formation of 7OHC ('2 h coumarin test'). Although four individuals had relatively slow coumarin test values (34-40%), no clear-cut polymorphism in the rate of 7OHC formation was found. However, 7OHC formation was lower in males and in cigarette smokers. PMID- 7875182 TI - Sedation with meperidine and midazolam in pediatric patients undergoing endoscopy. AB - We conducted a randomized, double-blind trial evaluating the efficacy and safety of meperidine 2 mg.kg-1 (M) and meperidine 2 mg.kg-1 plus midazolam 0.05 mg.kg-1 (M + M) in 40 pediatric outpatients (age 1 to 17 years) undergoing upper endoscopy procedures. The physician and nurse performing the procedure were asked to rate cooperation, emotional status, drowsiness, and overall efficacy. A blinded observer recorded the frequency of negative behaviors indicating distress, vital signs, and oxygen saturation before, during, and after the procedure. No significant differences were noted in the overall efficacy of the regimens. Good or excellent efficacy was noted in 15 of 21 children (71%) in the M group and 15 of 19 children (79%) in the M + M group by physicians; nurses assigned a good or excellent rating for 14 of 21 (67%) and 13 of 19 (68%) in the M and M + M groups, respectively. Immediately following the procedure, amnesia was noted in 4 of 17 (23%) patients who received M versus 14 of 18 (78%) patients who received M + M (P = 0.002). Of the children who received M + M, the amnesia tended to occur more frequently in older children (> 11 years, 8 children, rate of amnesia 100%) than in younger children (< or = 11 years, 6 of 10 evaluable children, rate of amnesia 60%). There was no significant difference between the frequency of negative behaviors, rate of adverse effects, or changes in vital signs or oxygen saturation noted with the two drug regimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875183 TI - Acute effect of ibopamine and isosorbide mononitrate on blood volume distribution in congestive heart failure. AB - In order to compare ibopamine (IBO), a dopamine congener, with isosorbide mononitrate (ISMN) and to study their interaction in effects on the capacitance vasculature in congestive heart failure (CHF), a prospective, randomized, placebo controlled, double-blind clinical trial was performed in 32 patients with New York Heart Association class II-IV CHF, randomly assigned to receive single oral doses of placebo, 200 mg IBO, 20 mg ISMN, or both IBO and ISMN. After labelling of red cells with 99mTc, changes in regional radioactivity, indicative of changes in blood volume, were recorded using a gamma-camera before and at 30, 60 and 120 min after drug administration. At 30 and 60 min, arterial systolic and pulse pressures were higher with IBO than with ISMN and placebo (for pulse pressure by mean 13.7 mmHg, 95% confidence interval 4.5-23.0 mmHg, at 30 min), probably reflecting an IBO-induced rise in stroke volume at unchanged heart rate and mean arterial pressure. IBO did not change regional radioactivity except for a transient increase of 4.4% (0.5-7.6%) in the thorax at 30 min. This was attenuated by concomitant ISMN treatment since, starting at 30 min, the drug increased radioactivity in the legs, compared with patients not receiving the drug, by 8.0% (95% confidence interval 0.2-15.8%), leading to a fall in thoracic and left ventricular radioactivity at 30 min of 3.4% (0.3-7.0%) and 6.4% (0.8 11.9%), respectively, and a fall of 5.5% (0.5-10.5%) in hepatic radioactivity at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875184 TI - The psychomotor and cognitive effects of a new antihistamine, mizolastine, compared to terfenadine, triprolidine and placebo in healthy volunteers. AB - Eighteen healthy volunteers received mizolastine 5 mg, 15 mg or 45 mg, terfenadine 60 mg, triprolidine 10 mg or placebo in a 6-way crossover, double blind study. Following each dose, subjects performed a series of tests of cognitive function and psychomotor performance at 1, 3, 5, 8 and 24 hours post dose. The test battery included critical flicker fusion, choice reaction time, tracking, Stroop and Sternberg memory tests and assessment of subjective sedation. Sedative effects and a concomitant reduction in psychomotor and cognitive function were observed following triprolidine, terfenadine and the highest dose of mizolastine, 45 mg, e.g. triprolidine reduced CFF threshold by 1.5 Hz and increased reaction time by 50 ms, impairments comparable to those caused by blood alcohol concentrations of 50 mg%, the legal limit in many countries. Mizolastine 5 mg did not differ significantly from placebo and at 15 mg differed only at one test point at one time. It may be concluded that mizolastine (5 mg and 15 mg) is free from disruptive effects on cognitive function and psychomotor performance, in contrast to terfenadine 60 mg, triprolidine 10 mg and mizolastine 45 mg. PMID- 7875185 TI - Influences of trospium chloride and oxybutynin on quantitative EEG in healthy volunteers. AB - Trospium chloride and oxybutynin are two antimuscarinergic agents used in the treatment of unstable bladder, urge incontinence, combined stress urge incontinence and detrusor hyperreflexia. The possibility that these two drugs produce changes in central nervous electrical activity was examined in an open, prospective, phase I study involving 12 volunteers. Quantitative evaluation of the multichannel electroencephalogram obtained from young healthy volunteers showed statistically significant decreases in alpha and beta 1 activity after oxybutynin, but not after intravenous or oral administration of trospium chloride. The biological activity of both drugs was ascertained by continuous simultaneous recording of the heart rate. A decrease in heart rate was detected after oral administration of oxybutynin, and an increase was seen after i.v. administration of trospium chloride. The results suggest that trospium chloride is less likely to produce central nervous adverse effects than to oxybutynin. PMID- 7875186 TI - Stereoselective inhibition by chloroquine of histamine N-methyltransferase in the human liver and brain. AB - This study was designed to determine whether both enantiomers of chloroquine inhibit histamine N-methyltransferase. The mean estimates of IC50 for the d- and l-enantiomers of chloroquine were 4.9 and 17.8 microM (liver), respectively and 6.9 and 21.6 microM (brain), respectively. Ki estimates were significantly lower with d- than with l-chloroquine; hence, d-chloroquine interacts with the enzyme more effectively than l-chloroquine. If the adverse effects of chloroquine are due to the inhibition of histamine N-methyltransferase, therapy with the l enantiomer might have lower toxicity. The residual activity of histamine N methyltransferase should reflect both the degree of inhibition by chloroquine and the level of enzyme expression. The rate of histamine methylation was measured in 100 human liver samples and its range and fold of variation were 29% and threefold, respectively. Susceptibility to chloroquine should be greater in subjects with limited expression of histamine N-methyltransferase PMID- 7875187 TI - A new isosorbide dinitrate extended-release formulation: pharmacokinetic and clinical parameters in patients with stable angina pectoris. AB - In a double-blind, cross-over study the acute clinical efficacy and pharmacokinetic profile of a newly developed isosorbide dinitrate extended release (ISDN-ER) formulation (10 mg immediate release and 60 mg slow release) were examined in eight angina patients. Exercise tests were done 1 h before and 1, 6 and 10 h after acute ISDN or placebo; similar testing was repeated after 14 days of open-labelled treatment. At 1, 6 and 10 h after administration, ISDN-ER significantly reduced the mean ST depression at highest comparable workload (HCWL) by 0.8, 0.6, and 0.6 mm, respectively. Total exercise duration increased significantly by 46, 42 and 72 s. The rate-pressure product at HCWL was not reduced significantly at any time, while digital plethysmography demonstrated a significant effect on arterial pulse curves throughout the 10 h. After 14 days of once-daily treatment, similar or somewhat attenuated clinical effects were observed. Pharmacokinetic measurements showed a first peak of ISDN at 1-2 h and a second peak at 4-5 h. The 5-isosorbide mononitrate (5-ISMN) metabolite peaked at 5-8 h and remained high at 10 h. After 14 days of treatment, the mean plasma concentrations of ISDN and 5-ISMN before drug were 0 and 69 ng.ml-1, respectively. Thus, satisfactory acute clinical efficacy and low nitrate levels during the night were observed. However, long-term clinical efficacy needs to be established in larger, placebo-controlled trials. PMID- 7875188 TI - Early stage autoinduction of carbamazepine metabolism in humans. AB - Six healthy young adult male volunteers were given two 600 mg (2540 mu moles) oral doses of carbamazepine (CBZ) 5 days apart. Serial concentrations of CBZ and its 10,11-epoxy (CBZ-epoxide) and 10,11-dihydro-10,11-trans-dihydroxy (CBZ-diol) metabolites in plasma, and daily excretions of these substances and the 2-hydroxy (2-OH-CBZ), 3-hydroxy (3-OH-CBZ) and 9-hydroxymethyl-10-carbamoylacridan (acridan) metabolites in urine were followed for 5 days after each dose. Pharmacokinetic analysis showed that autoinduction of CBZ metabolism was present within 6-10 days of the initial drug dose. The mean oral clearance of CBZ increased from 1.48 to 1.74 l.h-1 (difference 0.26 l.h-1, 95% confidence interval 0.11 to 0.41 l.h-1) and the mean percentage urinary recovery of the amount of CBZ eliminated increased from 41.8% to 44.6% (difference 2.8%, 95% confidence interval 0.5 to 5%) between the two studies 5 days apart. The data for daily clearance to metabolite and the time-courses of the plasma CBZ-epoxide to CBZ and CBZ-diol to CBZ concentration ratios suggested that autoinduction had begun by the second day after CBZ intake, and involved not only the epoxide-diol pathway but, to a lesser extent, the oxidations to phenolic derivatives. PMID- 7875189 TI - Effect of diet on the single- and multiple-dose pharmacokinetics of sustained release ketoprofen. AB - The indirect effect of diet on the single- and multiple-dose pharmacokinetics of sustained-release ketoprofen was studied in 16 healthy male volunteers. In an open, cross-over design, 200 mg ketoprofen was administered as a gastric-juice resistant, sustained-release tablet once daily during two periods of 5 days. A low-calorie/low-fat diet (LCFD) was given in the first period and a high calorie/high-fat diet (HCFD) in the second period. The first meal on each day was given 4 h after drug intake. Ketoprofen plasma concentrations were measured over 24 h after the first dose on day 1 and over 36 h after the final dose on day 5 of each period. On average, plasma concentrations of ketoprofen were higher with the LCFD than with the HCFD. With the HCFD there was a tendency to longer absorption lag times on day 5. The maximum concentration and the area under the curve over one 24-h dosage period (AUC0-24) were significantly higher with the LCFD, both on day 1 and on day 5. For AUC0-24 the differences were on average 15% (day 1) and 24% (day 5). The same tendency was observed for the amount excreted in urine over 24 h (Ae), but the difference was only significant on day 1 (14%). The elimination rate constant (K beta) and the mean residence time were similar for the two diets, both on day 1 and on day 5. From these results, we conclude that there was an acute indirect effect of diet when a meal was had 4 h after intake of the medication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875190 TI - Individualized drug utilization statistics. Analysing a population's drug use from the perspective of individual users. AB - The Danish retail pharmacies' drug subsidy system is completely computerized. The data are person-identifiable, making it possible to chart the population's drug use from the perspective of individual users. We decided to explore the potential of this data source and to analyse heavy drug users specifically. The analysis encompassed all 890,352 prescriptions presented by citizens of Odense in 1991. There was a total sales volume of 32 million defined daily doses consumed by 113,468 adult drug users, corresponding to 65.1% of the adult population. We found 2388 heavy drug users, defined by an annual purchase of more than 2000 defined daily doses. Heavy drug users accounted for 1.4% of the adult population and 22.9% of drug sales. They were remarkably well characterized by their main therapeutic class, which constituted a median of 47% of their drug use. A median of 97% of each heavy user's drugs were issued by one main prescriber. We conclude that heavy drug use can generally be ascribed to severe disease rather than to irresponsible prescribing. For the most important drug classes, we present various epidemiological measures of drug use, including 1-year prevalence, incidence, duration of therapy and some measures of skewness in utilization. If analysed regularly these measures can disclose subtle trends in clinical drug use that would not be evident from the wholesale figures. PMID- 7875191 TI - Lack of interaction between ramipril and simvastatin. AB - Twenty two healthy males participated in a randomised, placebo-controlled, double blind, cross-over study to investigate the influence of simvastatin on the pharmacokinetics of ramipril and its active metabolite (ramiprilat), and on the ACE-inhibiting effect of ramiprilat. During two study periods, each of 7 days, subjects received daily either simvastatin 20 mg at 19.00 h or placebo; ramipril (5 mg) was given on Day 5 of each of the periods. Plasma concentrations of ramipril and ramiprilat and ACE-activity were measured in sequential blood specimens, and ramipril and ramiprilat concentrations were measured in urine. Blood and urine collections for pharmacokinetic and pharmacodynamic assessment were made up to 72 h after the dose of ramipril. The mean AUC of ramipril for ramipril+placebo (R+P) and ramipril+simvastatin (R+S) was 22.2 and 21.3 ng.h.ml 1, respectively; for ramiprilat the corresponding figures were 61.3 and 57.6 ng.h.ml-1. The urinary excretion of ramipril+metabolites for (R+P) and (R+S) was 25.2 and 24.1% of dose. The maximum percentage inhibition of ACE-activity for (R+P) was 94.6%, and for (R+S) it was 94.1%. It is concluded that concomitant administration of simvastatin and ramipril has no clinically relevant effect on the pharmacokinetics or ACE-inhibition of the latter drug and its metabolites. PMID- 7875192 TI - A serotonergic mechanism for the metoclopramide-induced increase in aldosterone level? PMID- 7875193 TI - Characterization of the protein tyrosine phosphatase CD45 on human epidermal Langerhans cells. AB - Human Langerhans cells (LC) express CD45, but clear data about the isoform(s) and their function(s) are lacking. In the present study, double labeling experiments reveal that freshly isolated LC from normal skin are CD45RO+/RA-/RB-. However, after isolation and short-time culture where LC undergo an in vitro maturation resembling that to lymphoid dendritic cells, CD45RB emerges whereas CD45RO expression decreases. This evolution results from dynamic alternative RNA splicing. Addition of granulocyte-macrophage colony-stimulating factor or tumor necrosis factor-alpha to short-time cultures has no significant effect on CD45RB, but both cytokines accelerate the loss of CD45RO. LC isolated from lesional skin of atopic eczema highly express CD45RO and CD45RB. Cross-linking of CD45 on LC isolated from atopic individuals inhibits the calcium mobilization in response to activation via Fc epsilon receptor type I (Fc epsilon RI). Hence, the protein tyrosine phosphatase CD45 from human LC is subjected to a splicing phenomenon related to the differentiation and activation stage of these cells and regulates their Fc epsilon RI-mediated activation. PMID- 7875194 TI - Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection. AB - We have studied the patterns of antigens recognized by autologous cytolytic T lymphocytes (CTL) on two melanoma cell lines derived from metastases that were removed from patient LB33 at several years distance. Cell line LB33-MEL.A was obtained after surgery in 1988. A large number of CTL clones directed against LB33-MEL.A was obtained with blood lymphocytes collected from the patient in 1990. In vitro selection of melanoma cells that were resistant to these CTL clones indicated that at least five different antigens were recognized on LB33 MEL.A by autologous CTL. Four of these antigens were found to be presented by HLA A28, B13, B44 and Cw6, respectively. The patient remained disease-free until 1993 when a metastasis was detected and was used to obtain cell line LB33-MEL.B. This cell line proved resistant to lysis by all the CTL clones directed against the LB33-MEL.A cells and showed no expression of HLA class I molecules except for HLA A24. Using LB33-MEL.B cells to stimulate blood lymphocytes collected from the patient in 1994 we derived CTL clones that lysed these cells. All these CTL clones recognized a new antigen presented by HLA-A24. These results suggest that in patient LB33 the melanoma cells may have lost the expression of several HLA molecules under the selective pressure of an anti-tumor CTL response. PMID- 7875195 TI - Influence of interleukin-6 (IL-6) autoantibodies on IL-6 binding to cellular receptors. AB - Neutralizing autoantibodies to interleukin-6 (aAb-IL-6) have been reported in healthy individuals, in patients with autoimmune diseases, and in pharmaceutically prepared pooled IgG (IVIg). We investigated the ability of aAb IL-6 derived from IVIg to interfere with IL-6 binding to the undifferentiated monocytic cell line U-937. High-affinity aAb-IL-6, primarily of the IgG1 subclass, constituted approximately 1:10(6) of the total IgG in IVIg preparations. IL-6 binding to cellular receptors was strongly inhibited by one class of aAb-IL-6. These antibodies recognized epitope(s) on IL-6 essential for the binding of IL-6 to the alpha subunit of the IL-6 receptor (IL-6R). Another class of aAb-IL-6 recognized epitope(s) on IL-6, which is not essential for the binding to IL-6R but nevertheless important for the formation of high-affinity cellular IL-6 binding. These antibodies presumably interfered with the association of IL-6 receptor beta chains (gp130) with IL-6/IL-6R complexes, implicating that small IL-6/aAb-IL-6 immune complexes bound saturably (low affinity/high capacity) to cellular IL-6 receptors. There was no detectable binding of IL-6 through aAb-IL-6 and Fc receptors on U-937, and IVIg had no direct IL-6 receptor antagonizing activity. Dissociation kinetics of IL-6/aAb-IL 6 complexes at 37 degrees C revealed that IL-6 was liberated from 75% of the aAb IL-6 with a half-time (t/2) approximately 4 h but bound almost irreversibly to the remaining aAb-IL-6 (t/2 > 20 h). Cellular IL-6 uptake and degradation was suppressed by aAb-IL-6. Taken together, the data suggest that loss of immunologic tolerance against IL-6 might be a novel physiological mechanism by which IL-6 activities are effectively attenuated. Finally, binding of IL-6 in complex with IgG1 aAb-IL-6 on cells expressing IL-6 receptors implicates that such cells could be targets of antibody-dependent immunological reactions, including cytotoxic reactions. PMID- 7875196 TI - T cell receptor gamma delta repertoire is skewed in cerebrospinal fluid of multiple sclerosis patients: molecular and functional analyses of antigen reactive gamma delta clones. AB - To study the relevance of gamma delta T cells in multiple sclerosis (MS) we analyzed the T cell receptor (TCR) gamma delta repertoire and the antigen reactivity of gamma delta clones isolated from cerebrospinal fluid (CSF). In T cell cultures derived from CSF we found an increased percentage of V delta 1+ cells as compared to peripheral blood of the same donors. Phenotypic analysis of cells from MS CSF with V gamma- and V delta-specific monoclonal antibodies (mAb) showed that the V delta 1 chain is most frequently associated with gamma chains belonging to the V gamma 1 family. Sequence analysis of TCR genes revealed heterogeneity of junctional regions in both delta and gamma genes indicating polyclonal expansion. gamma delta clones were established and some recognized glioblastoma, astrocytoma or monocytic cell lines. Stimulation with these targets induced serine esterase release and lymphokine expression characteristic of the TH0-like phenotype. Remarkably, these tumor-reactive gamma delta cells were not detected in the peripheral blood using PCR oligotyping, but were found in other CSF lines independently established from the same MS patient. Altogether, these results demonstrate that in the CSF there is a skewed TCR gamma delta repertoire and suggest that gamma delta cells reacting against brain-derived antigens might have been locally expanded. PMID- 7875197 TI - Critical role of endogenous Mtv in acute lethal graft-versus-host disease. AB - Little is known about the etiology of the graft-versus-host disease (GVHD) occuring after transplantation of lymphoid cells incompatible for minor histocompatibility antigens (mHAg). Here, the potential role of host endogenous mouse mammary tumor virus (Mtv)-encoded superantigens (SAg) in the development of lethal GVHD was investigated. In a combination of H-2d compatible mice, the presence of Mtv-7 and, to a lesser extent, of Mtv-1, -6, -13 in the host genome, highly increases the rate and severity of GVHD. Kinetic analyses of TCR V beta gene expression in recipient mice consistently indicate a dramatic but transient infiltration of GVHD target organs by Mtv-SAg-specific T cells. This suggests that SAg encoded by endogenous Mtv, by activating large T cell subpopulations, would help the response to mHAg and thus play a critical role in the initiation or aggravation of GVHD. PMID- 7875198 TI - p40, a novel surface molecule involved in the regulation of the non-major histocompatibility complex-restricted cytolytic activity in humans. AB - Four monoclonal antibodies (mAb) termed NKTA255, NKTA72, 1F1 and 1B1 were selected on the basis of their ability to inhibit the cytolytic activity of natural killer (NK) cell clones against P815 target cells. These mAb selectively reacted with normal or tumor cells of hematopoietic origin and displayed a cellular distribution similar to that of CD45 or CD11a/CD18 antigens. Immunoprecipitation experiments showed that they reacted with molecules with an apparent molecular mass of 40 kDa under both reducing and nonreducing conditions ("p40" molecules), thus differing from CD45 or CD11a/CD18 antigens as well as from the "inhibitory" receptors for HLA class I molecules (i.e. p58, CD94 and NKB1 molecules). Double-immunofluorescence analysis of peripheral blood mononuclear cells allowed the identification of three distinct populations on the basis of the fluorescence intensity of cells stained with anti-p40 mAb. p40bright cells were homogeneously HLA-DR-positive, p40medium cells were HLA-DR-negative but co-expressed CD56 antigens, while p40dull cells were all CD3+. Anti-p40 mAb strongly inhibited the lysis of K562 target cells, mediated by fresh NK cells, as well as the lysis of P815 target cells by NK or T cell clones. In addition, in redirected killing assays, anti-p40 mAb strongly reduced the anti-CD16 mAb induced cytolytic activity of NK cell clones. On the contrary, they did not inhibit either the anti-CD3 or anti-T cell receptor mAb-mediated cytolytic activity of T cell clones or the lysis of allogeneic phytohemagglutinin blasts mediated by specific cytolytic T cell clones. The p40-induced inhibition of the NK cytotoxicity required optimal cross-linking, as anti-p40 mAb could inhibit the lysis of Fc gamma receptor (Fc gamma R)-positive but not of Fc gamma R-negative target cells. In addition, (Fab')2 fragments of anti-p40 mAb failed to inhibit the lysis of Fc gamma R-positive target cells. In conclusion, p40 molecules represent a new type of inhibitory surface molecule that appears to play a general regulatory role in the NK-mediated cytolysis. PMID- 7875199 TI - Immune response to Mycobacterium bovis bacille Calmette Guerin infection in major histocompatibility complex class I- and II-deficient knock-out mice: contribution of CD4 and CD8 T cells to acquired resistance. AB - Knock-out mice with defined major histocompatibility complex (MHC) deficiencies were infected intravenously with Mycobacterium bovis bacille Calmette Guerin (M. bovis BCG) to assess the relative impact of MHC class I- and II-dependent immune responses. Heterozygous control mice were capable of controlling growth of M. bovis BCG, although infection progressed chronically, as assessed by determination of colony-forming units. Furthermore, infected controls developed granulomatous lesions at the site of mycobacterial growth and delayed-type hypersensitivity (DTH) reactions after challenge with purified protein derivative of tuberculin. In vitro, spleen cells from heterozygous control mice produced high concentrations of interferon-gamma (IFN-gamma) after restimulation with mycobacterial antigens. In contrast, the MHC class II-deficient A beta-/- mice, which are virtually devoid of functional CD4 T cells, succumbed to M. bovis BCG infection. Furthermore, A beta-/- mice lacked DTH reactions to tuberculin and only few minute picnotic lesions were formed in livers of infected mice. Finally, spleen cells from infected A beta-/- mice failed to produce measurable IFN-gamma concentrations after restimulation in vitro with various mycobacterial antigen preparations. The capacity of beta 2-microglobulin (beta 2m)-deficient mice, which are devoid of CD8 alpha/beta T cells, to inhibit growth of M. bovis BCG was only slightly affected at low inocula, although significantly higher colony forming units were detected in spleens. These knock-out mice developed strong DTH responses to tuberculin and their spleen cells produced high levels of IFN-gamma once reactivated by mycobacterial antigens. Furthermore, in livers of infected beta 2m-deficient mice, extravascular infiltrates developed which were more diffuse than those in infected control littermates. Remarkably, the beta 2m deficient mice were substantially more susceptible to higher inocula of M. bovis BCG than their control littermates. Our data formally prove the essential role of MHC class II-dependent immune mechanisms in all relevant aspects of immunity to M. bovis BCG. In addition, our findings emphasize an important contribution of MHC class I-dependent immunity to effective anti-mycobacterial protection. We assume that CD4 T cells are highly effective in containing M. bovis BCG within distinct granulomatous lesions, but fail to eradicate their intracellular pathogens. It appears most likely that CD8 T cells are also required to achieve this goal. PMID- 7875200 TI - Induction of interleukin-2 transcription by the hamster polyomavirus middle T antigen: a role for Fyn in T cell signal transduction. AB - The transforming protein of mouse polyomavirus, the mouse middle T antigen (MomT), and its counterpart in the hamster polyomavirus, the hamster middle T antigen (HamT), interact with a number of cellular proteins. Among these are members of the Src family of tyrosine kinases, the phosphatidylinositol 3-kinase, the serine/threonine phosphatase PP2A and the adaptor protein Shc (in the case of MomT). However, both the relative affinity of these antigens for the members of the Src family and the tumor profile induced by their respective viruses are quite distinct. Particularly noteworthy are the preferential binding of Fyn by HamT and the induction of lymphoid malignancies by the hamster polyomavirus. Here we report that, when expressed in fibroblasts, HamT also associated with phospholipase C gamma (PLC gamma), which led to an increased intracellular concentration of inositol-1, 4, 5-trisphosphate. We also show that expression of HamT in the mouse T cell line EL4 was sufficient to induce transcription from interleukin-2 (IL-2), NFAT and NF kappa B reporter constructs. The immunosuppressant FK506 as well as dominant negative alleles of Ras and Raf inhibited HamT-induced IL-2 transcription. This, together with the observation of NFAT responses, suggests that the action of HamT depended at least in part on the integrity of signal transduction pathways elicited by activated PLC gamma. Furthermore, dominant negative Fyn but not the equivalent allele of Lck blocked HamT activation of IL-2 transcription, while both Lck and Fyn dominant negative alleles blocked LT cell receptor-mediated IL-2 transcriptional activation. These results support the hypothesis that Fyn is involved in signal transduction events leading to IL-2 transcriptional activation in T cells. Finally, the activation of IL-2 transcription by HamT and not by MomT shown here parallels the ability of the hamster polyomavirus to induce lymphoid malignancies. PMID- 7875201 TI - Reconstitution of a functional interleukin (IL)-7 receptor demonstrates that the IL-2 receptor gamma chain is required for IL-7 signal transduction. AB - The interleukin (IL)-2 receptor gamma chain has recently been shown to be a component of the IL-7 and IL-4 receptors. Using a transient transfection assay and the trans-activation of reporter gene constructs which are under the control of cytokine-responsive promoter elements, we have studied signal transduction through the IL-7 receptor (IL-7R). The reporter gene expression was not stimulated by receptors that contained the cytoplasmic domain of the IL-7R, either as intact IL-7R or as part of a chimeric receptor. However, co-expression of the IL-7R with the IL-2 receptor gamma chain was able to stimulate gene activation. For maximal stimulation the intact cytoplasmic domains of each chain was required. PMID- 7875202 TI - Alpha E beta 7 and alpha 4 beta 7 integrins associated with intraepithelial and mucosal homing, are expressed on macrophages. AB - The two beta 7 integrins alpha E beta 7 and alpha 4 beta 7 are the most recently described members of the integrins participating in intercellular binding. Their expression has been shown to be restricted to leukocytes and they have been suggested to be predominantly found in lymphocytes associating with the epithelium. Expression of beta 7 has mainly been studied on lymphocytes whereas macrophages have been reported not to express the beta 7 integrins. In this paper we have studied the expression of beta 7 integrins in monocytoid cells. The myelomonocytic cell lines HL-60 and THP-1 did not express beta 7 mRNA or protein, but differentiation of these cell lines to macrophages with phorbol 12-myristate 13-acetate (PMA) led to a strong induction of the beta 7 mRNA expression. A clear but less pronounced up-regulation of beta 7 mRNA-expression was also seen after treatment of HL-60 and THP-1 cells with interferon-gamma (IFN-gamma). However, its up-regulating effect on the surface expression of alpha 4 beta 7 and alpha E beta 7 complexes (detected by the monoclonal antibodies Act I and HML-1, respectively) exceeded that observed with PMA. To verify the in vitro cell line observations with normal cells, we also studied peripheral blood monocytes and tissue macrophages. Peripheral blood monocytes were Act I- and HML-1- in flow cytometry, but their expression was increased after a 72-h culture in the presence of PMA or IFN-gamma. Also, several Act I+ and HML-1+ macrophages were found in immunohistochemical stainings of both liver and edemic lung biopsies as well as in lymph node sinuses. We therefore conclude that while monocytes do not express beta 7 integrins the more differentiated cells of the monocyte-macrophage lineage do express both the alpha 4 beta 7 and alpha E beta 7 integrins, which might play a role in their intraepithelial homing. PMID- 7875203 TI - Mouse thymus dendritic cells: kinetics of development and changes in surface markers during maturation. AB - The early thymus precursor population of adult mice has the capacity to generate T cells, B cells and dendritic cells (DC). These precursors were injected into the thymus of irradiated recipients in order to follow the kinetics of thymic DC development. The resultant cohort of T-lineage cells developing in the thymus was accompanied by a parallel cohort of DC, present at 10(3)-fold lower frequency. The intrathymic lifespan of these DC was as short as that of T-lineage thymocytes. As the thymic DC matured, some markers characteristic of the original precursor population gradually declined (Ly-5, c-kit, Sca-2) whereas markers characteristic of thymic DC appeared and were maintained (major histocompatibility complex class II, CD11c, NLDC-145 and CD8 alpha). Some thymic DC expressed the early B-cell marker BP-1, and BP-1 mRNA, throughout their maturation. The surface markers on thymic DC could be divided into two groups. Some markers, including class I and class II MHC, CD8 alpha and BP-1, appeared to be integral components of the DC surface. In contrast, other markers, including Thy-1, CD4 and CD8 beta, had probably been picked up from associated thymocytes. PMID- 7875204 TI - Hypomethylation of the interferon-gamma gene correlates with its expression by primary T-lineage cells. AB - To determine the potential role of methylation in the regulation of interferon gamma (IFN-gamma) gene transcription by T cells, primary T-lineage cell populations were analyzed for the extent of methylation of three CpG sites within or near transcriptional activator elements in the 5' flank and first intron of the human IFN-gamma gene. A striking correlation was observed between the capacity of the IFN-gamma gene to be expressed and the degree of hypomethylation. The IFN-gamma gene was virtually completely methylated at all sites in thymocytes, neonatal T cells, and adult CD45RAhiCD45R0lo (antigenically naive) CD4 T cells, cell types that all have a low or undetectable capacity to express the IFN-gamma gene. In contrast, there was substantial hypomethylation in T lineage cell types with relatively high capacities to express the IFN-gamma gene, including adult CD8 T cells and adult CD45RAloCD45R0hi (memory/effector) CD4 T cells. These results suggest that hypomethylation of the IFN-gamma genetic locus may be an important determinant of IFN-gamma gene expression in vivo by T-lineage cells. PMID- 7875205 TI - Functional gap junctions in thymic epithelial cells are formed by connexin 43. AB - A multiparametric study was carried out to investigate the presence and possible role of communicating junctions in the thymus, particularly in the thymic epithelium, the major component of the thymic microenvironment. The presence of direct cell-cell communication mediated by gap junctions was demonstrated in human and murine thymic epithelial cells (TEC) by means of in situ and in vitro immunohistochemical labeling as well as in vitro fluorochrome injection and double whole-cell patch clamp experiments. Moreover, both immuno- and Northern blot studies revealed that the gap junction protein connexin 43 and its mRNA were present in TEC. Importantly, we showed that thymic endocrine activity, as ascertained by thymulin production, could be specifically down-modulated in vitro by a gap junction inhibitor, octanol. We also investigated the existence of gap junctions between TEC and thymocytes. In thymic nurse cells we were able to detect cell-cell communication, although only a minor percentage of epithelial/thymocyte pairs were coupled in a given moment. In contrast, intercellular communication was not detected between cultured phagocytic cells of the thymic reticulum and the respective rosetting thymocytes. We suggest that gap junctions formed by connexin 43 may represent a novel (and rather cell type specific) pathway for intrathymic cellular communication, including TEC/TEC as well as possible TEC/thymocyte interactions. PMID- 7875206 TI - Thymic epithelium induces full tolerance to skin and heart but not to B lymphocyte grafts. AB - Athymic nude mice reconstituted at birth with allogeneic thymic epithelia (TE) from day 10 embryos (E10), show life-long specific tolerance to skin and heart grafts, but eliminate B lymphocytes of the TE donor haplotype, nearly as well as those from a third strain. Previous immunizations with B cells do not alter the state of tolerance to skin grafts, but specifically accelerate elimination of lymphocytes. In contrast, transplantation of E15 allogeneic thymuses already seeded by hematopoietic cells resulted in chimeras tolerant to both skin and B lymphocytes. In vitro reactivities towards stimulator spleen cells of the haplotype of the thymus were observed in both E10 TE and E15 thymus chimeras. We conclude that induction of full in vivo tolerance to B cells requires hematopoietic cells, while this is not the case for induction of tolerance to skin and heart tissues; furthermore, in vitro reactivity to stimulator spleen cells of the tolerized haplotype is independent of in vivo tolerance. PMID- 7875207 TI - Precursor B cells of mouse bone marrow express two different complexes with the surrogate light chain on the surface. AB - Two monoclonal antibodies raised against the complex of mu heavy (H) chain and Vpre-B/lambda 5 surrogate light (L) chains recognize surrogate L chain in different conformations on normal pre-B cells. One, LM34 recognizes free lambda 5 protein and free lambda 5/Vpre-B surrogate L chains and binds to surrogate L chains on the surface of early, pro-B and pre-B-I cells where the surrogate L chain is associated with a gp130/gp35-65 complex of proteins. It also recognizes the surrogate L chain associated with the mu H chain on pre-B-II cells. The other monoclonal antibody, SL156, does not recognize free surrogate L chain or its components, nor its complex with gp130/gp35-65 on pro-B and pre-B-I cells. However, it does bind to a conformational epitope on the surrogate light chain/mu H chain complex on a subpopulation of pre-B-II cells and on mu H chain-positive pre-B cell lines. On mouse precursor B cells prepared ex vivo on ice, expression of the surrogate L chain is very low and almost undetectable. Incubation of the precursor cells for 1 h at 37 degrees C up-regulates the surface expression of surrogate L chain associated with gp130/gp35-65 (early complex) as well as the mu H chain/surrogate L chain complex. These results reconcile some of the apparently discrepant results on surface expression of the surrogate L chain obtained with human and mouse bone marrow pre-B cells, and show that a surrogate L chain/mu H chain-containing pre-B cell receptor can be expressed also on the surface of mouse pre-B-II cells. PMID- 7875208 TI - Crossrecognition by CD8 T cell receptor alpha beta cytotoxic T lymphocytes of peptides in the self and the mycobacterial hsp60 which share intermediate sequence homology. AB - Immunization of C57BL/6 mice with the mycobacterial heat shock protein (hsp) 60 in immunostimulating complexes caused the in vivo activation of autoreactive major histocompatibility complex class I (H-2Db)-restricted CD8 T cell receptor (TcR) alpha/beta cells. A CD8 TcR alpha/beta clone with specificity for the mycobacterial hsp60 peptide499-508 was derived from this immunization, which, in addition, recognized syngeneic macrophages which had been stressed by interferon gamma (IFN-gamma) stimulation. The stress-induced, self peptide could be extracted from IFN-gamma-stressed macrophages by acid elution, suggesting that the IFN-gamma-induced self peptide is derived from an endogenous protein. Based on our observation that lysis of stressed target cells by this cytotoxic T lymphocyte (CTL) clone was specifically inhibited by hsp60-specific antisense oligonucleotides, we used synthetic peptides representing amino acid (aa) sequences of the murine hsp60 for target cell sensitization and identification of the relevant self peptide. Synthetic peptides representing 9-mer to 11-mer aa sequences of the murine hsp60 with asparagine in anchor position 4 or 5 as the minimal requirement for H-2Db binding were tested in CTL assays. The overlapping murine hsp60 peptides162-170/171 were stimulatory at a concentration as low as 10 100 pM. Seven other peptides of the murine hsp60 required intermediate peptide concentrations of 10-100 nM for recognition by the CTL clone. Although the murine and mycobacterial hsp60 peptides recognized by this CTL clone showed only intermediate homology (3 identical and 3 similar aa), our data suggest that endogenous hsp60 itself is the source of self peptide(s) presented by IFN-gamma stressed macrophages to the cross-reactive CTL clone with promiscuous specificity. This notion is consistent with the idea of hsp as a link between infection and autoimmunity. PMID- 7875209 TI - Epitope mapping and functional properties of anti-intercellular adhesion molecule 3 (CD50) monoclonal antibodies. AB - Intercellular adhesion molecule-3 (ICAM-3, CD50), a member of the immunoglobulin gene superfamily, is a major ligand for the lymphocyte function-associated antigen 1 (LFA-1, CD18/CD11a) in the resting immune system and plays a role as a signaling and costimulatory molecule on T lymphocytes. In this study we have generated a large panel of anti-ICAM-3 monoclonal antibodies (mAb) and show that the biological effects of these antibodies are critically dependent on the epitope recognized. By using an adhesion assay employing COS cells expressing LFA 1 binding to recombinant chimeric ICAM-3-Fc proteins (which overcomes the confounding effects of interleukocyte LFA-1/ICAM binding events), we have been able to examine the effects of these antibodies in blocking LFA-1/ICAM-3 adhesion. Our data suggests that only a small minority of ICAM-3 mAb, recognizing a distinct epitope, are able to mimic the effects of LFA-1 binding to ICAM-3. Moreover these antibodies are functionally distinct as defined by their costimulatory activity and ability to elicit interleukin-2 production and cell proliferation in T lymphocytes. PMID- 7875210 TI - Murine macrophage scavenger receptor: in vivo expression and function as receptor for macrophage adhesion in lymphoid and non-lymphoid organs. AB - Macrophage scavenger receptors are trimeric integral membrane glycoproteins which have been implicated in various macrophage functions including uptake of oxidized lipoprotein and the serum-dependent, divalent cation-independent adhesion of macrophages to tissue culture-treated plastic. In this study we have used a recently defined monoclonal antibody (2F8) which recognizes murine macrophage scavenger receptor, to explore its expression in lymphoid and non-lymphoid organs of the normal adult. Scavenger receptor was detected in the red pulp and marginal zone of normal adult mouse spleen, medulla of the thymus and subcapsular region of lymph nodes. Kupffer cells in the liver, alveolar macrophages in the lung and lamina propria macrophages in the gut all reacted with 2F8 monoclonal antibody. The antigen was not detected on any non-macrophage cells, with the exception of sinusoidal endothelial cells in the liver. In the spleen, lymph node and liver, scavenger receptor antigen expression was associated specifically with phagocytic cells which had taken up colloidal carbon. To examine macrophage adhesion in a context relevant to the interactions occurring within lymphoid and non-lymphoid organs, and the contribution of macrophage scavenger receptor to this adhesion, we designed an assay of macrophage adhesion to frozen tissue sections. Adhesion to most tissues was high and uniform in the absence of any chelating agents. The chelation of Ca2+ and Mg2+ revealed specific patterns of macrophage adhesion in lymphoid and non-lymphoid organs which was completely inhibited by 2F8. The ability of this antibody to block the EDTA-resistant adhesion correlated with tissue expression of the antigen in some tissues. Unlike adhesion to tissue culture-treated plastic, macrophage scavenger receptor-dependent adhesion of macrophages to frozen tissue sections did not exhibit an absolute requirement for exogenous fetal bovine serum indicating the presence of an endogenous ligand for scavenger receptor within the tissues. We propose that macrophage scavenger receptor is a candidate homing or retention molecule for macrophage localization within ligand-rich tissues. PMID- 7875211 TI - Fc gamma receptor-mediated phagocytosis requires tyrosine kinase activity and is ligand independent. AB - Receptors for the invariant chain of immunoglobulins (FcR) define the cellular response to specific antigens. Fc gamma R recognize IgG and so elicit a variety of effector functions including phagocytosis. We are interested in the structural determinants for Fc gamma R-mediated phagocytosis, specifically Fc gamma RI(p135) and Fc gamma RIIa isoforms. The low-affinity receptor, Fc gamma RIIa, is found on macrophages and its cytoplasmic domain contains a tyrosine activation motif which has previously been shown to regulate endocytosis. In contrast, Fc gamma RI has no known signaling motifs, though a functional interaction has recently been demonstrated with the gamma chain of the high-affinity receptor for IgE, Fc epsilon RI. This accessory molecule has a cytoplasmic tyrosine activation motif implicated in signal transduction. Here we demonstrate that although Fc gamma RI transiently expressed on COS-7 cells is able to rosette opsonized SRBC, it cannot phagocytose them. If the cytoplasmic domain of either gamma chain or Fc gamma RIIa replaces that of Fc gamma RI in a chimeric receptor, efficient phagocytosis occurs. This particle ingestion is sensitive to the tyrosine kinase inhibitor genistein. Chimeric receptors where the extracellular domain of either Fc gamma RI or Fc gamma RIIa is replaced with that of CD2, a T cell antigen, indicate that Fc gamma R-mediated phagocytosis is ligand independent. We conclude that phagocytosis is dependent upon close particle apposition, tyrosine kinase activity, and that the process is ligand independent. PMID- 7875213 TI - Cytokine expression and regulation of human plasma cells: disappearance of interleukin-10 and persistence of transforming growth factor-beta 1. AB - Less is known about the cytokine expression and regulation of normal plasma cells compared to that of activated B cells or myeloma cells. This study shows that nonproliferating (hydroxyurea-treated), immunoglobulin (Ig)-secreting cells generated from human B cells in the EL-4 culture system no longer express interleukin (IL)-6 mRNA, progressively lose IL-10 mRNA, but continue to express transforming growth factor (TGF)-beta 1 mRNA. Secretion of TGF-beta 1 protein was demonstrated. On the other hand, and in contrast to the suppression of B cell proliferation and Ig secretion, the basal or the IL-6/IL-10 stimulated Ig secretion of nonproliferating cells was not inhibited by recombinant TGF-beta 1. Plasma cells isolated from human bone marrow expressed neither IL-6 nor IL-10 mRNA; only TGF-beta 1 mRNA was detected by reverse transcription-polymerase chain reaction analysis. Such plasma cells may be on average more "aged" cells than those generated in vitro. Thus, plasma cells persistently express TGF-beta 1, a known suppressor of various lymphoid and hemopoietic cell activities, but do not limit their own Ig secretion via this cytokine. PMID- 7875212 TI - Regulation of 4-1BB expression by cell-cell interactions and the cytokines, interleukin-2 and interleukin-4. AB - 4-1BB expression increased gradually following T cell activation, and by day 3 post-stimulation with immobilized anti-CD3 (anti-CD3i) or concanavalin A (Con A), splenic T cells were routinely 35-45% 4-1BB+ by flow cytometric analysis. 4-1BB was expressed on activated CD8+, CD4+, CD28+ and CD45RB+ T cells. Optimal 4-1BB expression was seen by day 6 post-stimulation and was cell density dependent. When T cells were cultured for 6 days at 1 x 10(6)/well in a 24-well plate with anti-CD3i, 82% of the cells were 4-1BB+. In contrast, at lower cell densities (4 x 10(5), 2 x 10(5) and 1 x 10(5)), optimal 4-1BB expression was observed only if the cultures were supplemented with recombinant interleukin-2 (IL-2) or recombinant IL-4 (IL-4). In agreement, with these results, modes of inducing endogenous IL-2 production such as cross-linking the costimulatory molecule, CD28, or the addition of syngeneic accessory cells to T cells activated with anti CD3i, resulted in high levels of 4-1BB expression. The addition of interleukin-1 alpha (IL-1 alpha) or interferon-gamma (IFN-gamma) did not increase 4-1BB expression on anti-CD3i-activated T cells. In addition, if T cells were incubated with IL-2, IL-4, IL-1 alpha, IFN-gamma or anti-CD28 alone, no 4-1BB expression was induced. T cells activated with soluble anti-CD3 (anti-CD3s) in the presence of IL-2, IL-4, or accessory cells, did not express higher levels of 4-1BB on their cell surface. These data suggest that initial events crucial for efficient T cell activation, such as signals delivered through the T cell receptor/CD3 complex and the CD28 molecule, are instrumental in regulating subsequent 4-1BB expression. PMID- 7875214 TI - Distribution of HLA class II molecules in epidermal Langerhans cells in situ. AB - We performed immunoelectron microscopic studies to investigate the expression of HLA class II molecules in Langerhans cells (LC). In the epidermis, LC expressed class II molecules on the plasma membrane of the dendrites, resulting in a class II positive reticulo-epithelial network, but not on the surface of the cell body. In contrast, isolated LC as well as activated LC in situ displayed an even and strong expression of class II molecules on their entire cell surface. Therefore, isolation and/or activation results in redistribution and up-regulation of class II molecules on the cell surface. In addition, double-labeling experiments were carried out with monoclonal antibodies to class II antigens and to LAMP-1, CD63 and alpha-glucosidase, specific markers for organelles of the endosomal/lysosomal system. The results show expression of class II molecules on intracellular, electron-dense vesicular structures, and co-localization of class II molecules and the markers for late endosomes and early lysosomes in human LC in situ. Expression of these markers was not found on Birbeck granules, an LC-specific organelle. PMID- 7875215 TI - Inhibition of CD28-mediated T cell costimulation by the phosphoinositide 3-kinase inhibitor wortmannin. AB - T lymphocyte activation requires at least two signals, one via the antigen specific T cell receptor and a second via the surface molecule CD28 which provides signals critical to interleukin-2 (IL-2) production and T cell proliferation. We have previously shown (Ward S. G., Westwick, J., Hall N. and Sansom D. M. Eur. J. Immunol. 1993. 23: 2572) that CD28 stimulates phosphoinositide (PI) 3-kinase activity, indicating that D-3 phosphoinositides may act as mediators of CD28-induced T cell costimulation. Here, we report that immunoprecipitation of CD28 molecules from Jurkat cells stimulated with the CD28 ligand B7, results in a ligand-dependent association of CD28 with PI 3-kinase. This association correlates with the appearance of PI 3-kinase enzymatic activity in CD28 immunoprecipitates and the formation of D-3 phosphoinositides. Consistent with the hypothesis that D-3 phosphoinositides are important mediators of CD28 signaling, treatment of T cells with the PI 3-kinase inhibitor wortmannin, inhibited both T cell proliferation and production of IL-2, but not the response of T cells to exogenous IL-2. Hence, abrogation of PI 3-kinase activity by wortmannin, appears sufficient to disrupt the costimulatory pathway utilized by CD28, indicating a central role for this enzyme in the CD28 signaling pathway. PMID- 7875216 TI - Phosphatidylinositol 3-kinase activity is not essential for CD28 costimulatory activity in Jurkat T cells: studies with a selective inhibitor, wortmannin. AB - The interaction of CD28 with its counter-receptor, B7-1 (CD 80), on antigen presenting cells induces a co-signal in T cells required to promote antigen dependent interleukin-2 (IL-2) production and to prevent clonal anergy. CD28 stimulation causes both protein-tyrosine kinase and phosphatidylinositol3-kinase (PI3-K) activation, suggesting a possible role for these enzyme activities in CD28 co-signal transduction. Here, we investigate the effect of wortmannin, a selective and irreversible PI3-K inhibitor on CD28 co-signaling events in the Jurkat T cell line. Wortmannin added to cell cultures partially inhibits CD28 induced tyrosine phosphorylation of the putative p110 catalytic subunit of PI3-K, but does not block CD28-induced association of the p85 PI3-K regulatory subunit with the CD28 receptor. Wortmannin inhibits in a dose-dependent manner both total cellular PI3-K activity and CD28-induced receptor-associated PI3-K activity. Wortmannin (1 microM) inhibits cellular PI3-K activity by 90% with complete inhibition achieved at 10 microM. The inhibitory effect of wortmannin on cellular PI3-K activity is prolonged ( > 18 h), suggesting that the drug is not readily metabolized by Jurkat T cells. Wortmannin, at concentrations that blocked PI3-K activity, fails to inhibit the synergistic effect of CD28 on IL-2 secretion in the presence of phorbol 12-myristate 13-acetate and ionomycin. These data demonstrate that CD28-induced signaling events other than the activation of PI3-K catalytic activity contribute to the control of IL-2 secretion. PMID- 7875217 TI - Carbohydrate-dependent, HLA class II-restricted, human T cell response to the bee venom allergen phospholipase A2 in allergic patients. AB - The T cell-independent antibody response to polysaccharide antigen (Ag) is believed to result from their inability to bind major histocompatibility complex (MHC) restriction elements. However, recent studies using glycosylated analogues of known immunogenic peptides revealed that glycopeptides can interact with MHC molecules and are able to elicit specific T cell responses in experimental animals. This raises questions about the possible role which carbohydrates can play in T cell responses following natural exposure to glycoprotein antigens. Analyzing the fine specificity of the human T cell response against the major bee venom allergen phospholipase A2 (PLA), a 16-20-kDa protein glycosylated at a single site (Asn13), we have identified several T cell clones which proliferate in response to the glycoprotein but not to its non-glycosylated variants. Neither the carbohydrate moiety alone nor the combination of carbohydrate and non glycosylated protein could substitute for the intact glycoprotein. Antibody directed against the carbohydrate moiety inhibited Ag-induced proliferation of these clones whereas control clones with known peptide specificity were not affected, providing additional evidence for the involvement of carbohydrates in T cell recognition. Moreover, peripheral blood mononuclear cells of two individuals from whom glycosylation-dependent T cell clones have been isolated showed significantly higher proliferation in response to glycosylated compared to non glycosylated Ag, suggesting that glycosylation can contribute in some cases extensively to the immunogenicity of a glycoprotein Ag. Thus, this report shows that glycosylation-dependent Ag recognition by T cells can also occur following natural exposure to a glycoprotein. PMID- 7875218 TI - Expression of TAP1 by human trophoblast. AB - Successful placentation in the human is dependent on the trophoblast evading recognition and destruction by the maternal immune system. However, invasive cytotrophoblast express HLA-G which may be able to present peptide to T cells. Transporter proteins are essential for peptide presentation and major histocompatibility complex (MHC) class I assembly. We have determined their expression by trophoblast in relation to HLA-G, using immunohistochemistry. Anti transporter protein antibody (TAP1) labeling closely paralleled that of MHC class I, but the intensity of its expression was much greater on the HLA-G+ extravillous cytotrophoblast than any other fetal or maternal tissue in the first trimester and at term. This suggests that the extravillous cytotrophoblast are very actively assembling MHC class I antigens with peptides. However, expression of MHC class I by the cytotrophoblast was not correspondingly elevated. This pattern could result from HLA-G being shed from the surface of the trophoblast, a process which may play a central role in protecting the fetus from maternal immune attack. PMID- 7875219 TI - Ovalbumin injected with complete Freund's adjuvant stimulates cytolytic responses. AB - CD8+ cytotoxic T lymphocytes (CTL) recognize antigens (Ag) associated with class I major histocompatibility complex (MHC) molecules. Endogenously synthesized protein Ag are processed into peptides in the cytoplasm and transported to the endoplasmic reticulum where they are bound by class I proteins. Exogenous Ag do not enter the class I processing pathway of most cells and thus do not activate CD8+ CTL. Nevertheless, several investigators have reported that immunization with exogenous Ag can activate CD8+ T cells that have immunoregulatory activity. To determine how exogenous Ag entered the class I pathway in vivo and whether immunosuppressive CD8+ T cells were cytolytic, we have shown in this report that injection with OVA emulsified in the complete Freund's adjuvant (CFA) primed CD8+, class I MHC-restricted, OVA-specific CTL in mice. These CTL recognize the OVA257-264 epitope, produce tumor necrosis factor-alpha and interferon-gamma upon activation. Both oil and mycobacteria components in CFA were required for inducing CTL responses. Priming was not attributed to direct sensitization of class I-bearing cells by contaminating peptides. Rather, phagocytic cells, but not CD4+ helper T cells, were required for priming CD8+ CTL by OVA-CFA. Thus, OVA in CFA is taken up by antigen-presenting cells and processed into the class I pathway by phagocytic cells in vivo. In addition, CTL induced by OVA-CFA suppressed the antibody response to OVA in adoptive recipients. These results suggest that CD8+ CTL specific for exogenous proteins might be routinely stimulated by injecting proteins in conventional adjuvants and that such cells have the potential to regulate immune responses in vivo. PMID- 7875220 TI - Genes encoded in the major histocompatibility complex affecting the generation of peptides for TAP transport. AB - The B cell line 721.174 has lost the ability to present intracellular antigens to major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL). This phenotype results from a homozygous deletion in the MHC that includes the peptide transporter genes TAP1 and TAP2, and the proteasome subunits LMP2 and LMP7. Recent work has shown that such cells transfected with TAP genes load their class I molecules with endogenous peptides, and present several viral epitopes to class I-restricted CTL. These data implied that the LMP2 and LMP7 genes were not required for the presentation of most epitopes through class I molecules. By contrast, while confirming the previous reports, we have identified several epitopes that appear to require genes in the MHC in addition to the TAP for their presentation. Further analysis localizes the defect to proteolysis in the cytosol. In one case, presentation could be partially restored by re-expression of full-length LMP7. Control experiments with LMP7, from which the putative pro region had been removed, failed to restore presentation, and this lack of effect correlated with failure of the shortened LMP7 to incorporate into the proteasome. These results suggest a role for LMP7 in the generation of a viral epitope, but leave open the possibility that additional genes within the .174 deletion are required for full restoration of antigen presentation. PMID- 7875221 TI - The third component of Xenopus complement: cDNA cloning, structural and functional analysis, and evidence for an alternate C3 transcript. AB - Although the third component of complement has been purified from two amphibian species, Xenopus laevis and the axolotl, only limited information is available about its primary structure in these species. We now present (a) 95% of the cDNA sequence encoding C3 from a Xenopus laevis/Xenopus gilli (Xenopus LG) hybrid (b) an analysis of the C3 convertase and factor I cleavage sites in Xenopus C3, and (c) evidence for an alternative form of C3. The Xenopus LG sequence has a 57% nucleotide and 52% amino acid sequence identity to human C3 and contains one potential N-glycosylation site in the beta-chain. The deduced amino acid sequence showed that the C3 convertase and factor I cleavage sites (Arg-Ser) are conserved in Xenopus C3 and protein sequencing of Xenopus C3 fragments fixed on zymosan during complement activation demonstrated that Xenopus C3 is indeed cleaved by C3 convertase and factor I at these sites. Our screening of a liver cDNA library identified an unusual C3 clone with a deletion of 2502 bp, suggesting the presence of a novel C3 transcript in Xenopus LG liver. The presence of this C3 transcript was confirmed by reverse transcription polymerase chain reaction using Xenopus LG liver mRNA and specific oligonucleotide probes. This transcript encoded a putative 102-kDa protein comprising the beta-chain of C3, together with the first 59 residues and the last 103 residues of the alpha-chain; it would therefore lack many of the ligand binding sites found in the intact alpha-chain. However, the molecule may be an analog of a truncated C3 molecule that is found in the serum of allergic dermatitis patients and acts as an inhibitor of eosinophil cytotoxicity and neutrophil adherence. PMID- 7875222 TI - CD28 activation promotes Th2 subset differentiation by human CD4+ cells. AB - Ligation of CD28 provides a costimulatory signal to T cells necessary for their activation resulting in increased interleukin (IL)-2 production in vitro, but its role in IL-4 and other cytokine production and functional differentiation of T helper (Th) cells remains uncertain. We studied the pattern of cytokine production by highly purified human adult and neonatal CD4+ T cells activated with anti-CD3, phorbol 12-myristate 13-acetate (PMA) and ionomycin, or phytohemagglutinin (PHA) in the presence or absence of anti-CD28 in repetitive stimulation-rest cycles. Initial stimulation of CD4+ cells with anti-CD3 (or the mitogens PHA or PMA+ionomycin) and anti-CD28 monoclonal antibodies induced IL-4, IL-5 and interferon-gamma (IFN-gamma) production and augmented IL-2 production (6 to 11-fold) compared to cells stimulated with anti-CD3 or mitogen alone. The anti-CD28-induced cytokine production corresponded with augmented IL-4 and IL-5 mRNA levels suggesting increased gene expression and/or mRNA stabilization. Most striking, however, was the progressively enhanced IL-4 and IL-5 production and diminished IL-2 and IFN-gamma production with repetitive consecutive cycles of CD28 stimulation. The enhanced Th2-like response correlated with an increased frequency of IL-4-secreting cells; up to 70% of the cells produced IL-4 on the third round of stimulation compared to only 5% after the first stimulation as determined by ELISPOT. CD28 activation also promoted a Th2 response in naive neonatal CD4+ cells, indicating that Th cells are induced to express a Th2 response rather than preferential expansion of already established Th2-type cells. This CD28-mediated response was IL-4 independent, since enhanced IL-5 production with repetitive stimulation cycles was not affected in the presence of neutralizing anti-IL-4 antibodies. These results indicate that CD28 activation may play an important role in the differentiation of the Th2 subset in humans. PMID- 7875223 TI - gamma delta lineage-specific transcription of human T cell receptor gamma genes by a combination of a non-lineage-specific enhancer and silencers. AB - The expression of the T cell receptor (TcR) gamma genes is restricted to TcR gamma delta + T lymphocytes. Transgenic and somatic cell hybrid experiments had suggested that the expression of a functionally rearranged TcR gamma gene was extinguished in TcR alpha beta + T cells, possibly by putative cis-acting transcriptional silencers. We have identified such negative cis-acting sequences in the 3' non-coding region of the human TcR gamma (TRG) locus, upstream of an enhancer located at 6.5 kb of the TcR C gamma 2 gene (TRGC2). These silencers were capable of repressing the transcription from a minimal heterologous promoter in a position- and orientation-independent fashion. When analyzed individually, the silencers and the enhancer were equally active in the TcR alpha beta + and TcR gamma delta + T cell lines studied. In contrast, the association of the enhancer with either silencer was shown to restrict transcription to the TcR gamma delta + T cell lines. PMID- 7875224 TI - Induction in vitro of a primary human antiviral cytotoxic T cell response. AB - We report herein the successful priming of human anti-viral cytotoxic T cells (CTL) in vitro using two induction strategies based on the stimulation of peripheral blood mononuclear cells isolated from uninfected donors with synthetic viral peptides. The peptides used contain HLA-A2 binding motifs and have been identified as HLA-A2-restricted CTL epitopes in patients infected by the hepatitis B and C viruses. One approach uses repetitive long-term stimulation and the other uses bulk cultures containing large numbers of naive peripheral blood mononuclear cells. Both approaches successfully induce HLA-A2-restricted CTL specific for several viral epitopes. Some CTL recognize endogenously synthesized antigen on target cells infected with recombinant vaccinia virus expressing the corresponding viral proteins. This simple technique permits easy analysis of the primary human CTL repertoire, and may be exploitable for production of specific CTL effector cells for adoptive immunotherapy and dissection of the cellular and molecular requirements for priming of naive human CTL. PMID- 7875225 TI - The nude mutation results in impaired primary antibody repertoire. AB - We have studied the effect of the nude mutation and/or T lymphocytes on the development of V gene germ-line repertoire in neonatal athymic (nu/nu) and euthymic (+/nu) littermates. A total of 2.35 x 10(6) and 1.47 x 10(6) B lymphocyte clones from nu/nu and +/nu neonates, respectively, were examined for the expression of select VH (J558, J606, S107, 36-60, 7183 and Q52) and Vx (1, 2, 8 and 9) gene families as well as VH (J558, S107) + Vx (1, 9) associations. Data showed that the nude mutation, whether homozygous or heterozygous, significantly affects VH and Vx gene expression as well as VH and Vx pairings and, thus, provide evidence for a defective development of B cell repertoire in both athymic nude (nu/nu) and euthymic (+/nu) mice. In addition, an analysis of 3.34 x 10(6) B lymphocyte clones from adult C57BL/6 mice showed non-stochastic association between VHJ558 + Vx1 gene families that suggests restrictions on clonal population in order to maintain homeostasis in the immune system. Studies outlined here, therefore, describe an hitherto unknown defect in the development of B lymphocyte repertoire as a result of the nude mutation which is independent of thymic dysgenesis. PMID- 7875226 TI - Adenosine A1 receptors in the rat brain in the kindling model of epilepsy. AB - Adenosine and adenosine analogues have potent anticonvulsant effects on various seizure models, including kindling, an animal model of temporal lobe epilepsy. It is now reported that binding of a specific ligand (cyclohexyladenosine) to adenosine A1 receptors is not changed in the cerebral cortex of kindled rats. However, the affinity of cyclohexyladenosine to adenosine receptors is significantly increased in the hippocampus. In addition, cyclohexyladenosine is slightly more potent to inhibit [3H]D-aspartate outflow from hippocampal synaptosomes taken from kindled than from control rats. Taken together, these data suggest that an increased affinity of adenosine to A1 receptors may play a role in the anticonvulsant effect of adenosine A1 analogues in the kindling model. PMID- 7875227 TI - Prejunctional actions of N-ethyl-maleimide and phenoxybenzamine in rat vas deferens. AB - In studies of electrically evoked isometric contractions of rat vas deferens, N ethyl-maleimide (30 microM) pretreatment significantly reduced the prejunctional inhibitory potencies of xylazine and 5-hydroxytryptamine but failed to affect the potency of the alpha 1-adrenoceptor agonist amidephrine. Phenoxybenzamine (1 microM) or N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (10 microM) produced significant shifts in the potency of xylazine and significantly reduced the maximum inhibition, but the combination of phenoxybenzamine or EEDQ and N ethyl-maleimide (30 microM) produced no further alteration in the effects of xylazine. In displacement studies, N-ethyl-maleimide displaced the binding of [3H]MK 912 ((2S,12bS)1',3'-dimethylspiro- (1,3,4,5',6,6',7,12b-octahydro-2H benzo[b]furo[2,3-a]quinazoline)- 2,4'- pyrimidin-2'one) to rat renal cortex membranes with a Ki of 466 +/- 133 microM (n = 5), and so does not bind to alpha 2-adrenoceptors in the concentration range in which it affects prejunctional receptor mediated responses. This may suggest that N-ethyl-maleimide has actions other than inactivation of G-proteins or that the irreversible alpha 2 adrenoceptor antagonists phenoxybenzamine and EEDQ inactivate G-proteins sensitive to N-ethyl-maleimide in concentrations at which they bind to alpha 2 adrenoceptors. PMID- 7875228 TI - Alpha 1-adrenoceptor subtypes mediating the regulation and modulation of Ca2+ sensitization in rabbit thoracic aorta. AB - Norepinephrine (10 microM), methoxamine (100 microM) and clonidine (100 microM) with guanosine 5'-triphosphate (GTP, 50 microM) or guanosine 5'-O-(3 thiotriphosphate) (GTP gamma-S, 10 microM) all significantly enhanced the contraction induced by 0.3 microM Ca2+ (pCa6.5) in beta-escin-skinned smooth muscle of rabbit thoracic aorta. The enhancement of Ca2+ contraction produced by norepinephrine was greater than that produced by methoxamine or clonidine. In beta-escin-skinned strips of chloroethylclonidine-pretreated smooth muscle, the enhancement of Ca2+ contraction produced by norepinephrine was significantly decreased, whereas the amplitude was the same as that produced by methoxamine or clonidine; this enhancement was inhibited by the selective alpha 1A-adrenoceptor antagonist WB 4101 (100 nM). The enhancement of Ca2+ contraction produced by methoxamine and clonidine was not affected by chloroethylclonidine pretreatment. The effects of methoxamine, clonidine and norepinephrine in the chloroethylclonidine-pretreated tissue were all inhibited by guanosine 5'-O-(2 thiodiphosphate) (GDP beta-S, 1 mM) and 1-(5-isoquinolinylsulfonyl) methylpiperazine (H-7, 20 microM). Furthermore, the phosphorylation of myosin light chain produced by norepinephrine was greater than that produced by clonidine. These results suggest that both alpha 1-adrenoceptor subtypes (alpha 1A and alpha 1B) increase the Ca2+ sensitivity of contractile elements, and that the Ca2+ sensitization produced by alpha 1A-subtype receptors is mediated through G-protein and protein kinase C, and plays an important role in contraction of smooth muscle of rabbit thoracic aorta. PMID- 7875229 TI - Effects of NPC16377, a potent and selective sigma receptor ligand, on the activity of mesencephalic dopamine-containing neurons in the rat. AB - NPC16377 is a highly selective sigma receptor ligand with low affinity for other neurotransmitter receptors. Preclinical studies indicate that the drug exhibits a pharmacological profile similar to that previously ascribed to atypical antipsychotic drugs. In the present series of experiments, extracellular recording techniques were used to assess the acute effects of NPC16377 on the electrophysiological properties of mesencephalic dopamine-containing neurons in the rat. Systemic administration of NPC16377 produced marginal increases in the firing rate of these neurons but failed to fully reverse the inhibitory effects of the dopamine agonists apomorphine and d-amphetamine. Low doses of the drug potentiated the rate-decreasing effects of d-amphetamine in the substantia nigra but not in the ventral tegmental area. Some of these effects are similar to the actions of atypical antipsychotic drugs, while others appear to be unique to this compound and may involve a direct interaction with sigma sites. PMID- 7875230 TI - Characterization of a novel muscarinic receptor agonist, YM796: comparison with cholinesterase inhibitors in in vivo pharmacological studies. AB - Previous reports have shown that (+/-)-YM796 (2,8-dimethyl-3-methylene-1-oxa-8 azaspiro[4.5]decane) exhibits M1 agonistic activity and ameliorates cognitive impairment, and that the (-)-S isomer is active in in vitro studies. We report here the characterization of the (-)-S isomer, YM796 ((-)-(S)-2,8-dimethyl-3 methylene-1-oxa-8-azaspiro[4.5]decane L-tartrate monohydrate), and its (+)-R isomer in in vivo pharmacological studies in comparison with the cholinesterase inhibitors tacrine, amiridine and E-2020. YM796 (0.031-0.5 mg/kg p.o.), like the racemate, reversed the cognitive impairment in passive avoidance tasks of rats with nucleus basalis magnocellularis lesions, whereas (+)-R-YM796 was ineffective in this experimental amnesia. YM796 exhibited only weak effects on mouse salivation and hypothermia, a peripheral cholinergic response and a central cholinergic response, respectively. The (+)-R isomer, however, failed to induce these cholinergic responses. YM796 also ameliorated the memory deficits induced by scopolamine in rats and electroconvulsive shock in mice. The potency of YM796 in these experimental amnesia models was over a 100 times greater than that of tacrine, over 10 times greater than that of E-2020, and 6 times greater than that of amiridine. In salivary secretion and hypothermia, YM796 was 2-4 times weaker than tacrine and E-2020, and 1-2 times stronger than amiridine. Thus, YM796's ratio of anti-amnesic effects to salivary secretion and hypothermia was much greater than that of the cholinesterase inhibitors tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875232 TI - Blockade of ethanol discrimination by isradipine. AB - The effect of the dihydropyridine Ca2+ channel antagonist, isradipine, on ethanol discrimination was assessed in rats trained to discriminate 1.5 g/kg ethanol from water in a T-maze, food-reinforced drug discrimination procedure. Pretreatment with isradipine (0, 1.0, 3.0 and 5.0 mg/kg i.p.) resulted in a dose-dependent blockade of ethanol discrimination. The results of the present study suggest that L-type Ca2+ channels are involved in the mediation of ethanol discriminative stimulus effects. PMID- 7875231 TI - Effects of pimobendan, its active metabolite UD-CG 212, and milrinone on isolated blood vessels. AB - The effects of pimobendan, 2-(4-hydroxy-phenyl)-5-(5-methyl-3-oxo-4,5-dihydo-2H-6 pyridazinyl ) benzimidazole (UD-CG 212), and milrinone were investigated on isometric contraction of vascular preparations in rats and guinea-pigs. The drugs dose dependently relaxed aortic, carotid and femoral arterial and mesenteric venous preparations precontracted with KCl or norepinephrine. The rank order of potency (negative log EC50 value) for these drugs was dependent upon the sources of the preparations and stimulants used. The relaxation response to milrinone was reversible, that to UD-CG 212 was poorly reversible, and that to pimobendan was intermediate. Relaxation responses to cromakalim were inhibited by 0.1 microM glibenclamide, whereas those to pimobendan, UD-CG 212 and milrinone were inhibited by glibenclamide only at doses as high as 10-30 microM. The drugs potentiated the relaxation response to isoproterenol but not glyceryl trinitrate, and noncompetitively inhibited arterial contractions accompanied by voltage dependent Ca2+ influxes. It is suggested that the drugs are potent vasorelaxants, acting directly on vascular smooth muscle and that the vasorelaxant effects are mediated through cyclic AMP-dependent mechanisms. PMID- 7875233 TI - Morphine analgesia and tolerance in mice selectively bred for divergent swim stress-induced analgesia. AB - Morphine-induced analgesia and tolerance were examined in Swiss Webster mice selectively bred for high and low swim stress-induced analgesia. Morphine produced a dose-dependent analgesia in both lines; it was 4-fold more potent in the high analgesia line than in the low analgesia line. Despite the differences in morphine-induced analgesia, the degree of tolerance was the same in both lines. Together, these data suggest that selective breeding of mice for high and low swim stress-induced analgesia produced a striking difference in morphine induced analgesia without affecting the degree of tolerance. Thus, while there is a common genetic determination in swim stress-induced and morphine-induced analgesia, the development of tolerance to morphine possibly relies on a different genetic background. PMID- 7875235 TI - Felbamate antagonizes isoniazid- and FG 7142-induced reduction of GABAA receptor function in mouse brain. AB - Injection of the antiepileptic drug, felbamate (2-phenyl-1,3-propanediol dicarbamate), into mice reduced in a dose-dependent manner (150-300 mg/kg i.p.) the isoniazid (200 mg/kg s.c.)-induced increase in ex vivo binding of t [35S]butylbicyclophosphorothionate ([35S]TBPS) to cerebral cortical and hippocampal membranes. The same doses of felbamate reduced significantly the number of mice exhibiting isoniazid-induced seizures. A dose of felbamate (50 mg/kg) ineffective in isoniazid-treated mice completely antagonized the increase of [35S]TBPS binding elicited by FG 7142 (N-methyl-beta-carboline-3-carboxamide), a benzodiazepine receptor inverse agonist. The above effects of felbamate resembled those of diazepam. Accordingly, the combination of ineffective doses of felbamate (50 mg/kg) and diazepam (0.2 mg/kg) elicited a marked decrease of [35S]TBPS binding. The results indicate that facilitation of gamma-aminobutyric acid type A (GABAA) receptor function may play a role in the anticonvulsant action of felbamate. PMID- 7875234 TI - Modulation of mesolimbic dopamine release by the selective dopamine D3 receptor antagonist, (+)-S 14297. AB - In Chinese hamster ovary cells stably transfected with recombinant rat dopamine D2 or D3 receptors, the naphthofurane antagonist, (+)-S 14297 [(+)-[7-(N,N dipropylamino)-5,6,7,8-tetrahydro- naphtho(2,3b)dihydro,2,3-furane]], displayed a pronounced preference for dopamine D3 versus D2 receptors: Ki values = 13 and 365 nM, respectively. In contrast, its distomer, (-)-S 17777, showed low affinity (296 versus 3403 nM). The aminotetralin agonist, (+)-7-OH-DPAT (7-hydroxy-2-(di-n propylamino)tetralin), also showed high affinity at dopamine D3 (1.8 nM) versus D2 (96 nM) receptors while its (-)-isomer showed low affinity (71 and 1461 nM). In freely moving rats, (+)-7-OH-DPAT (0.16 mg/kg s.c.)-but not (-)-7-OH-DPAT decreased dialysate levels of dopamine in the nucleus accumbens. (+)-S 14297 (1.25 mg/kg s.c.) markedly inhibited the action of (+)-7-OH-DPAT without influencing dopamine levels alone. Further, this action was stereospecific in that (-)-S 17777 (20.0 mg/kg s.c.) was inactive. In conclusion, data obtained with the novel, selective dopamine D3 receptor antagonist, (+)-S 14297 suggest that dopamine D3 autoreceptors modulate the release of dopamine from mesolimbic dopaminergic neurones. PMID- 7875236 TI - Bioeducational marketing--a mask of properness. PMID- 7875237 TI - Developmental changes in the function of hematopoietic stem cells. AB - The observation that colony-forming unit-spleen (CFU-S) cells can be found in the yolk sac, fetal liver, and various hematopoietic tissues in adult mice has contributed to the concept that "stem cells" represent a single type of immortal cell that is present at variable numbers in tissues at different stages of development. However, more recent studies have shown dramatic changes in various functional properties of purified "candidate" stem cells during ontogeny. Together with previous studies documenting developmental changes in early hematopoietic cells and observations showing a decrease in the mean telomere length of chromosomes in hematopoietic cells during ontogeny, these findings are difficult to reconcile with the concept of a stem cell as an immortal and invariable cell type. In this minireview, some developmental aspects of stem cell biology are discussed in the context of stem cell definitions and transplantation biology. PMID- 7875238 TI - Enhancement of GVL effect with rhIL-2 following BMT in a murine model for acute myeloid leukemia in SJL/J mice. AB - A murine model for acute myeloid leukemia (mAML) was used to study graft-vs. leukemia (GVL) effects on residual leukemic cells across both major (MHC) and minor histocompatibility antigens (mHA) barriers. In addition, the therapeutic effect of recombinant human interleukin-2 (rhIL-2)-administered postsyngeneic and allogeneic bone marrow transplantation (BMT) was examined. SJL/J mice inoculated with mAML cells were exposed later to total body irradiation (TBI) and transplanted with bone marrow cells (BMC) mixed with spleen cells derived from normal syngeneic (SJL/J), congenic (B10.S), or allogeneic (C57BL/6) donor mice. One-half of the mice in each group received low dose rhIL-2 for 3 days starting 1 day post-BMT. Spleen cells from treated recipients were transferred to secondary naive SJL/J mice for in vivo detection of residual tumor cells. At a tumor load of 10(5) cells per animal, none of the mice rescued with SJL/J or B10.S cells was cured since 100% of secondary recipients developed leukemia. Concomitant treatment of recipients of B10.S cells with rhIL-2 induced GVL effects since none of the secondary recipients developed leukemia after 2 years. All adoptive recipients of mice rescued with C57BL/6 cells remained free of leukemia after 2 years whether or not rhIL-2 was injected. The potency of the GVL effects observed across mHA and MHC were tumor-cell dose dependent since fewer animals inoculated with 10(6) mAML cells were cured. Only marginal GVL effects were noticed following syngeneic BMT and rhIL-2. Our results sustain the importance of the GVL effects in the treatment of myeloid leukemia and demonstrate that immunotherapy with rhIL-2 following BMT can enhance the therapeutic effect induced by the allograft. PMID- 7875239 TI - Effects of activin A/erythroid differentiation factor on erythroid and megakaryocytic differentiations of mouse erythroleukemia (Friend) cells: evidence for two distinct modes of cell response. AB - To further characterize activin A/erythroid differentiation factor (EDF) action on hematopoietic cell differentiation, we examined the effects of activin A/EDF on megakaryocytic and erythroid differentiation by determining acetylcholinesterase (AchE) activity and hemoglobin production in the mouse erythroleukemia (MEL) cell line F55. Activin A/EDF induced AchE activity of F55 cells in a dose-dependent manner. Erythroid differentiation of F55 cells, which was characterized by an increase in dianisidine-positive cells, was also induced by activin A/EDF. The effect of activin A/EDF on hemoglobin synthesis appeared more slowly compared with the effect on AchE activity. Erythroid differentiation induced by activin A/EDF was affected by the initial cell density, but AchE activity was not. Sodium orthovanadate, a tyrosine phosphatase inhibitor, markedly inhibited activin A/EDF-induced erythroid differentiation but not activin A/EDF-induced AchE activity. Other erythroid differentiation inducers, sodium butyrate and butyrylcholine chloride, mildly increased AchE activity in F55 cells, but N,N'-hexamethylene-bis-acetamide (HMBA), dimethyl sulfoxide (DMSO), and genistein did not. Dexamethasone inhibited HMBA-induced erythroid differentiation but did not affect activin A/EDF or sodium butyrate action. These results suggest that F55 cells potentially can differentiate into cells of a megakaryocytic lineage in addition to an erythroid lineage, and that activin A/EDF further potentiates the cell differentiation of this cell line. In addition, our results suggest that the mode of activin A/EDF effects on megakaryocytic differentiation is distinct from that on erythroid differentiation. PMID- 7875240 TI - Constitutive and virus-induced interferon production by peripheral blood leukocytes. AB - The production of interferon-alpha (IFN-alpha) by normal human peripheral blood mononuclear cells (PBMNC) was studied using polyclonal antipeptide antibodies designed to react either with all IFN-alpha subtypes or with individual subtypes IFN-alpha 2 or IFN-alpha 4. In this study, we demonstrate the detection of intracellular IFN-alpha in PBMNC using immunofluorescence staining and flow cytometric analysis. Virtually all cells of the PBMNC population were shown to produce IFN-alpha reactive with all three antisera after stimulation with Sendai virus. The immunofluorescence studies also demonstrated that IFN-alpha is produced by PBMNC in the absence of known viral stimulation but is not secreted in detectable levels. Double-labeling with specific monoclonal antibodies to T and B lymphocytes confirmed that the entire populations of these two cell types produce IFN-alpha, both constitutively and after virus induction. Polymorphonuclear cells (PMNC) isolated from Ficoll-Paque pellets were also shown to contain intracellular IFN-alpha, both before and after virus induction. The finding that all PBMNC produce IFN-alpha constitutively suggests that IFN-alpha may have important regulatory functions in situations other than during overt viral infections. PMID- 7875241 TI - Detection of incorporated iododeoxyuridine in colonies by immunoperoxidase staining: a novel method to measure the proportion of cycling colony-forming cells. AB - In vitro suicide by tritiated thymidine (3H-TdR), hydroxyurea (HU), or cytosine arabinoside (Ara-C) is assumed to reflect the proportion of colony-forming cells in S-phase at the time of exposure. However, these techniques are not always accurate. Nonradioactive iododeoxyuridine (IdUrd) is incorporated into DNA during S-phase and can be detected by monoclonal antibodies. In the present study, a new IdUrd application was developed to investigate the kinetics of hematopoietic progenitor cells. After incubation with IdUrd, colony-forming cells were cultured in semisolid assay. An immunoperoxidase staining protocol was developed to detect IdUrd in cells of colonies in agar. Colony-forming cells in S-phase during the IdUrd exposure were postulated to give rise to IdUrd+ colonies, whereas non-S phase cells would generate IdUrd- colonies. Toxicity, sensitivity, and IdUrd inactivation studies indicated that progenitor cells could safely be pulse labeled for 2 hours with 40 microM IdUrd, whereas prolonged labeling with 1 microM IdUrd was at least feasible for 5 days. Molt-4 cells and normal bone marrow cells were used to compare IdUrd pulse-labeling with 3H-TdR suicide. Part of the Molt-4 cells were enriched for G1- and S-phase cells by counterflow centrifugation. The bone marrow cells were either unstimulated or stimulated with growth factors. As a result, the accuracy of both techniques could be tested in populations with different quantities of S-phase cells. Wide confidence intervals of the suicide technique contrasted with the small confidence intervals obtained with IdUrd pulse-labeling. For instance, the fraction of Molt-4 cells with 27.8% S-phase cells contained 17.7% (confidence interval -8.2 to 43.6%) clonogenic cells in S-phase when determined with 3H-TdR suicide. Of this fraction, the percentage of clonogenic cells in S-phase was 30.6% with a confidence interval of 25.5 to 36.2% when determined with IdUrd pulse-labeling. In our hands, the IdUrd pulse-labeling was more accurate than the 3H-TdR suicide technique. Thus far, kinetic studies of progenitors have been limited to the determination of the fraction of S-phase cells by suicide techniques. By prolonged IdUrd labeling, it is now possible to determine the proliferating fraction of progenitor cells. PMID- 7875242 TI - Phospholipid and fatty acid composition in stored sheep erythrocytes of different densities. AB - The mammalian erythrocyte is an ideal model for studies of membrane aging under conditions of storage. The present study describes the variations in the membrane lipid composition of three density groups (light, 1.110 < d < 1.125; intermediate, 1.125 < d < 1.130, and dense, 1.130 < d < 1.140) of sheep erythrocytes separated by centrifugation in a discontinuous Ficoll density gradient after storage at 4 degrees C in a nutrient medium for up to 6 days. The only changes in phospholipid composition took place in the erythrocyte light fraction where sphingomyelin (SM) and phosphatidic acid increased (p < 0.05), whereas phosphatidylethanolamine (PE) decreased (p < 0.05). Moreover, polyunsaturated fatty acids (20:4 and 22:6) decreased during storage, whereas lipid fluorescence increased (p < 0.01) after 24 hours of storage in all the fractions separated. These observations suggest a lipid peroxidation process in all three erythrocyte groups during storage. PMID- 7875243 TI - Modulation of apoptosis in human myeloid leukemic cells by GM-CSF. AB - Apoptosis (programmed cell death) regulates cell population size. To determine the mechanisms whereby hematopoietic growth factors (HGFs) modulate apoptosis in human myeloid leukemic cells, we evaluated the roles of protein and mRNA synthesis for altering apoptosis in growth factor-stimulated vs. quiescent leukemic TF1 cells. Lysates of cells from the granulocyte-macrophage colony stimulating factor (GM-CSF)-dependent myeloid leukemic cell line TF1 were separated into high molecular weight (HMW) pellets of intact DNA and supernatants of fragmented low MW (LMW) DNA, and the DNA purified from these fractions was quantified. In the absence of both GM-CSF and fetal bovine serum (FBS), 70% of the DNA was fragmented after 3 days in culture, with a characteristic apoptotic ladder-like pattern on agarose gel electrophoresis, whereas this proportion had initially been < 5%. In contrast, less than 5% of the DNA was fragmented in cells incubated with GM-CSF plus FBS or GM-CSF alone. Delayed addition of GM-CSF, but not FBS, permitted partial rescue of the cells, inhibiting increasing rates of accumulation of fragmented DNA. When the macro-molecular synthesis inhibitor cycloheximide (CHX) or actinomycin D (Act D) was present for 26 hours in the absence of GM-CSF and FBS, apoptosis was inhibited. In contrast, in the presence of GM-CSF or FBS, apoptosis was enhanced upon addition of CHX or Act D. The latter effect persisted even with the late addition of CHX. These findings indicate that disparate mechanisms of enhancing or inhibiting apoptosis exist in myeloid leukemic cells related to environmental conditions, including HGF regulated cellular synthesis of distinct proteins and mRNA. PMID- 7875244 TI - Technology of blood and marrow transplantation. PMID- 7875245 TI - Bone marrow transplantation for the treatment of hematologic diseases: status in 1994. PMID- 7875246 TI - Photodynamic sensitizers assay: rapid and sensitive iodometric measurement. AB - A rapid, sensitive and simple spectrophotometric method for the detection of 1O2 produced by photodynamic photosensitizers in slightly acid and air-saturated aqueous solutions has been developed. The method is based on the reaction of 1O2 (produced by photodynamic processes) with I- in the presence of ammonium molybdate as a catalyst. The reaction product I3-, proportional to 1O2, is followed spectrophotometrically at 355 nm. Several ways of avoiding interference with other oxidizing compounds, either present before or produced during the irradiation, are described. PMID- 7875247 TI - The effect of a phorbol ester upon the cholinergic regulation of potassium permeability in the rat submandibular gland. AB - Acetylcholine releases calcium from cytoplasmic stores and permits an influx of calcium in salivary acinar cells. The resultant rise in [Ca2+]i causes an increase in potassium permeability which is an important part of the secretory response. We have investigated the effects of 12-O-tetradecanoyl phorbol-13 acetate, a potent activator of protein kinase C, upon this regulation of potassium permeability in superfused pieces of rat submandibular salivary gland. This compound inhibited the initial [Ca2+]O-independent component of the response of acetylcholine but had no effect upon the subsequent [Ca2+]O-dependent phase. This compound does not, therefore, appear to inhibit receptor-regulated calcium influx. PMID- 7875248 TI - Zinc ions block the intracellular calcium release induced by caffeine in guinea pig taenia caeci. AB - Zn2+ in low concentrations (0.005-0.1 mM) inhibited the transient contractions in response to caffeine (25 mM) in a dose-dependent manner in smooth muscle of intact guinea-pig taenia caeci. At Zn2+ concentrations higher than 0.1 mM, caffeine did not elicit any response. After saponin-treatment of the fibres, which leaves the Ca2+ storage sites intact, caffeine contraction was completely inhibited by Zn2+ at a relatively low concentration (0.003 mM). However, in Triton-X-100-treated fibres, in which the Ca2+ release sites are destroyed, the contraction could be induced in the presence of Zn2+ by an increase in Ca2+. In conclusion, Zn2+ can block the intracellular Ca2+ release from caffeine-sensitive release sites in taenia caeci. PMID- 7875249 TI - Unexpected collagen crosslinking observed during in vitro radiolabeling of the galactosyl moiety. AB - Aldehyde groups, generated by oxidation of free primary alcohol groups of galactosyl residues of glycoproteins by galactose oxidase, can react with free amino groups on the polypeptide chain through Schiff base formation. Subsequent reduction with tritiated borohydride results in the formation of stable crosslinks instead of the expected generation of radiolabeled alcohol groups. Attempts to perform in vitro radiolabeling of collagen type I by this procedure resulted in undesirable crosslinking with profound alteration of the physical properties that rendered the resulting radiolabeled preparation unsuitable for biochemical studies. PMID- 7875250 TI - Expulsion of the placenta from the uterus is the principal initiator for collagen degradation in mouse uterus. AB - In unilaterally pregnant mice, collagen degradation in the non-pregnant uterine horn was not initiated by removal of the fetus only but by removal of both the fetus and placenta. The results indicate that expulsion of the placenta from the uterus is a principal factor in the initiation of the process of collagen degradation simultaneously in the whole uterus. PMID- 7875251 TI - Effect of temperature on in vitro proliferative activity of human umbilical vein endothelial cells. AB - Human umbilical vein endothelial cells, skin fibroblasts, and retinal pigment epithelial cells are cultivated in medium supplemented with 15 to 20% serum in our laboratory. The effects of various incubation temperatures on the proliferation of these cells was examined. Our study shows that the mitogenic response of the endothelial cells to a change of temperature differed markedly from that of the fibroblasts and epithelial cells. Cultivation of human umbilical vein endothelial at 37 degrees C required seeding densities as high as 1-2 x 10(4) cells/cm2, and yet resulted in a low growth rate and premature senescence. However, under the same culture conditions, but at 33 degrees C, the proliferative capacity of these endothelial cells was potentiated. The results were striking; at 33 degrees C the cells grew actively and the life span was extended. The number of cumulative population doublings increased fourfold compared with that for the same cells cultivated at 37 degrees C. The inoculum size could be reduced, since at 33 degrees C the endothelial cells were able to replicate at seeding densities as low as 20 cells/cm2. The cells serially subcultured at 33 degrees C retained morphological features and specific immunological markers of endothelial cells. PMID- 7875252 TI - Neurotrophic effects of conditioned media of astrocytes isolated from different brain regions on hippocampal and cortical neurons. AB - The present study was designed to reveal whether astroglial cells from different brain regions produce diffusible factors that differentially support the survival of neurons and the establishment of neuronal morphology. For this purpose, astrocyte conditioned media (ACM) were prepared by conditioning chemically defined medium with type I astrocyte culture dissociated from cerebral cortex, hippocampus and hypothalamus. Hippocampal and cortical neurons were cultured in ACM or in non-conditioned medium. ACM derived from three brain regions all supported the survival of hippocampal and cortical neurons better than non conditioned control medium. Of these, hypothalamic ACM was the most effective in supporting the survival of cortical neurons. The ACM also potentiated the elongation of the longest neurite of hippocampal and cortical neurons. However, there were no significant differences in the promoting effects on neurite elongation among ACM from three brain regions. PMID- 7875253 TI - Expression of multidrug resistance (mdr) gene(s) in primary lymphoid organs of chicken immune system during embryonic development. AB - The presence of a multidrug resistance (MDR) related protein, P-170, in normal and pathological lymphoid cells has been described. The present report evaluates the expression of the mdr 1 gene by using the reverse Polymerase Chain Reaction (PCR) on cells obtained from the thymus and bursa of chicken embryos starting from day 12 until hatching. Results show that the thymic cells are positive from day 12 to the end of the observation period. In contrast, mdr mRNA was detected in the bursa from day 14 to day 17 of embryonic life. Possible relationships between the expression of mdr and the development of T and B lymphocytes are discussed. PMID- 7875254 TI - Components of biological, including seasonal, variation in hematological measurements and plasma fibrinogen concentrations in normal humans. AB - This study has been carried out in order to examine the components of biological and, in particular, seasonal variation in hematologic measurements in normal humans. Toward this end, 26 normal volunteers had monthly blood samplings during one calendar year for determination of number of red blood cells (RBC) and platelets, hemoglobin (Hb), hematocrit (Ht), mean corpuscular volume (MCV), MC Hb (MCH), MC Hb concentration (MCHC), RBC distribution width (RDW), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), and plasma fibrinogen concentrations. The data were analyzed by means of spectral analyses of a group of time series or a single time series, and by means of repeated measures analyses of variance. Most of the hematologic variables show seasonal rhythms, such as annual rhythms or harmonics, which are expressed as a group phenomenon. An important part of the variance ( > 15%) in Ht, MCV, MCH, MCHC, RDW, number of platelets, MPV and plasma fibrinogen was explained by a yearly variation. The peak-trough differences (expressed as a percentage of the mean) in the yearly variations in number of RBC, Ht, MCV, MCH, MCHC and RDW were very low (all < 8.5%). Number of platelets (14.4%) and plasma fibrinogen values (28%) showed a high-amplitude yearly variation. All hematological variables, except MCHC, show a high interindividual variability which exceeds by far the intraindividual variability. PMID- 7875255 TI - Allele-specific PCR reveals that CYP6D1 is on chromosome 1 in the house fly, Musca domestica. AB - A cytochrome P450, termed P450lpr, is the major P450 responsible for pyrethroid resistance in the Learn-PyR (LPR) strain of house fly. Recently, the putative gene (CYP6D1) coding for P450lpr has been sequenced from the LPR and aabys strains of house fly. Allele-specific polymerase chain reaction (ASPCR) was used for linkage group analysis with backcross progeny from the wild type LPR strain and a multiple marker strain (aabys). We found that CYP6D1 is linked to chromosome 1. The possible role of regulatory or modifying genes responsible for elevated P450lpr expression is discussed in relation to the chromosomal linkage of CYP6D1. PMID- 7875256 TI - Analysis of the relationship between age of larvae at mutagen treatment and frequency and size of spots in the wing somatic mutation and recombination test in Drosophila melanogaster. AB - The relationship between the induction of mutant clones and the time of mutagen treatment was studied in the somatic mutation and recombination test (SMART) in wing cells of Drosophila melanogaster. Larvae trans-heterozygous for the recessive marker mutations multiple wing hairs (mwh) and flare (flr) were produced. Batches of these larvae were then treated with mutagen at different ages spanning all three larval instars. Methyl methanesulfonate was fed acutely for 2 h by immersing the larvae in a solution of the mutagen mixed with powdered cellulose. Wings of the surviving adult flies were mounted and scored for the presence of spots. The frequency and size of single and twin spots were recorded separately. Twin spots are produced exclusively by mitotic recombination, whereas single spots can result from various types of mutational and exchange events. There exists a clear correlation between time of induction and frequency as well as size of the single spots. In young larvae only few but very large spots are induced, whereas in older larvae the frequencies are considerably increased but the sizes are smaller. The twin spots show a different relationship. Practically no twin spots are found in very young and in very old larvae. The results demonstrate that in the wing spot test the optimal age of the larvae for mutagen treatment is 72 h. PMID- 7875257 TI - Chromosomal evolution and zoogeographic origin of southeast Asian shrews (genus Crocidura). AB - To the origins and evolution of Indomalayan shrews, we investigated the chromosomal variations of 14 species of Crocidura from SE Asia. Intraspecific polymorphism was mainly due to variation in the number of short chromosomal arms but C. lepidura and C. hutanis showed a polymorphism due to a centric fusion. The undifferentially stained karyotypes were similar in 9 species, all possessing 2n = 38 and FN = 54-56 (68); C. fuliginosa had 2n = 40 and FN = 54-58. These karyotypes are close to the presumed ancestral state for the genus Crocidura. Four species from Sulawesi had a reduced diploid number (2n = 30-34), a trend not observed among other SE Asian species but present in few Palaearctic taxa. Compared to the apparent stasis of karyotypic evolution observed among other SE Asian species, the high degree of interspecific differences reported among Sulawesian shrews is unusual and needs further investigation. Stasis and reduction in diploid number found in both Indomalayan and Palaeractic species suggest that these two groups share a common ancestry. This is in sharp contrast to most Afrotropical species which evolved towards higher diploid and fundamental numbers. The zoogeographical implications of these results are discussed. PMID- 7875259 TI - Use of in vivo nasal transepithelial potential difference to evaluate efficacy in CF gene therapy phase I trials. PMID- 7875258 TI - Alzheimer's disease: fundamental and therapeutic aspects. AB - Alzheimer's disease is the most common type of progressive and debilitating dementia affecting aged people. In some early--as well as late--onset familial cases, a genetic linkage with chromosomes 14, 21 (early-onset) or 19 (late-onset) has been indicated. Furthermore, a direct or indirect role has been attributed to normal or structurally altered amyloid beta-protein (concentrated in senile plaques) and/or excessively phosphorylated tau protein (located in neurofibrillary tangles). Degeneration of cholinergic neurons and concomitant impairment of cortical and hippocampal neurotransmission lead to cognitive and memory deficits. Several compounds are being tested in attempts to prevent and/or cure Alzheimer's disease, including tacrine, which has very modest efficacy in a sub-group of patients, and new acetylcholinesterase inhibitors. Pilot experiments have also been launched using nerve growth factor (NGF) to prevent or stabilize the processes of cholinergic pathway degeneration. Alternatively, antioxidants, free radical scavengers and/or non steroidal anti-inflammatory agents may be screened as potential therapies for neurodegenerative diseases induced by multiple endogenous and/or exogenous factors. The recent use of transgenic mice, in parallel with other genetic, biochemical and neurobiological systems, in vivo and/or in vitro (cell cultures), should accelerate the discovery and development of specific drugs for the treatment of Alzheimer's disease. PMID- 7875260 TI - Novel approaches to the diagnosis of mycobacterial infections. PMID- 7875261 TI - Pseudomonas-induced neutrophil recruitment in the dog airway in vivo is mediated in part by IL-8 and inhibited by a leumedin. AB - A bacteria-free supernatant of Pseudomonas aeruginosa induces the production of neutrophil chemotactic activity in human bronchial epithelial cells in vitro that is due to the potent chemotactic factor, interleukin-8 (IL-8). Because P. aeruginosa supernatant itself is not chemotactic, we hypothesized that intratracheal P. aeruginosa induces the production of neutrophil chemotactic factors, including IL-8, in vivo. Because neutrophils play a key role in cystic fibrosis, inhibition of neutrophil recruitment might be therapeutic. We studied the effect of P. aeruginosa supernatant in the isolated tracheal segment of dogs in vivo, and we measured neutrophil chemotactic activity in vitro in the tracheal fluid. We also determined the local effect of intratracheal administration of leumedin NPC 15669, an inhibitor of neutrophil recruitment, on IL-8- and Pseudomonas-induced neutrophil accumulation. P. aeruginosa supernatant and IL-8 both caused time-dependent accumulation of neutrophils in the tracheal fluid. Tracheal fluid obtained after P. aeruginosa administration had neutrophil chemotactic activity in vitro that was significantly inhibited by the IL-8 antibody. Intratracheal NPC 15669 prevented both IL-8- and Pseudomonas-induced accumulation of neutrophils. We conclude that P. aeruginosa supernatant recruits neutrophils into the airway indirectly by inducing the production of chemotactic factors, including IL-8. Our results suggest a potential therapeutic role for leumedins in chronic airway diseases. PMID- 7875262 TI - Early decrease of serum Clara cell protein in silica-exposed workers. AB - Clara cell protein (CC16) is a 16 kDa protein secreted by nonciliated cells of the tracheobronchial tree; it has recently been proposed as a peripheral marker of respiratory epithelial injury. The concentration of CC16 was measured in the serum and, when available, in the sputum of 86 miners exposed to silica and of 86 control subjects matched for age, body mass index and smoking status (26 lifelong nonsmokers and 60 current smokers in both groups). Workers were exposed to silica rich dust in a quarry for 15.2 months on average. No difference between exposed and control workers could be detected with regard to respiratory symptoms, chest radiographs or lung function tests. By contrast, the concentration of CC16 in serum was decreased in silica-exposed workers (geometric mean 12.3 micrograms.l 1) compared to controls (16.3 micrograms.l-1). The decrease was found both in lifelong nonsmokers (14.7 vs 21.9) and current smokers (11.3 vs 14.5). In the latter, tobacco smoking caused a decrease of serum CC16 that was additional to that associated with silica exposure. The determination of CC16 in sputum samples, judged to be reliable on the basis of the CC16/alpha-amylase concentration ratio (mostly from smokers), also revealed a reduction of CC16 following silica exposure (46.2 vs 106 mg.l-1). We conclude that alterations in the serum concentrations of CC16 probably reflect very early toxic effects of silica particles on the respiratory epithelium. This reinforces the view that serum CC16 is a sensitive marker, which might improve our ability to detect exposure to chemicals potentially harmful to the respiratory tract. PMID- 7875263 TI - Loss of lymphocyte modulatory control by surfactant lipid extracts from acute hypersensitivity pneumonitis: comparison with sarcoidosis and idiopathic pulmonary fibrosis. AB - Surfactant components are recognized to exert a regulatory control on lymphocytes in physiological conditions, as testified by in vitro studies. However, what happens following lung injury has not been established. As surfactant composition is altered in interstitial lung diseases, this work was carried out to compare the modulatory impact of normal human alveolar fluids on lymphocyte proliferation, with that from inflammatory lung diseases which are characterized by distinct patterns of immunologically-mediated alterations (i.e. sarcoidosis, acute hypersensitivity pneumonitis, idiopathic pulmonary fibrosis). Thymidine incorporation of allogeneic normal human blood lymphocytes was studied in the presence of total alveolar fluids or lipid extracts from 37 subjects, and phytohaemagglutinin (PHA) as T-cell mitogen. The results show that: 1) total alveolar fluids and lipid extracts from normal subjects share a concentration dependent suppressive activity on T-cell proliferation; 2) total alveolar fluids from diseased patients have lost this property, either by a lack of suppressive activity (i.e. idiopathic pulmonary fibrosis) or even by enhanced activity (i.e. sarcoidosis and hypersensitivity pneumonitis); 3) lipid extracts from diseased patients still retain the suppressive activity of normal subjects, except for hypersensitivity; and 4) an imbalance in surfactant phospholipids with an increase in the inducers to suppressors ratio is more likely to explain this alteration in hypersensitivity pnuemonitis than changes in total lipid content. In conclusion, alveolar lipid extracts from acute hypersensitivity pnuemonitis have lost the modulatory control normally exerted by surfactant lipids on lymphocyte proliferation in vitro. This alteration may contribute to the invasion of the lung by lymphocytes in acute hypersensitivity pnuemonitis in vivo. PMID- 7875264 TI - Determinants of response to immunosuppressive therapy in idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) response to corticosteroids and cytotoxic medications appears to be the most important determinant of survival. The purpose of this retrospective study was to analyse the determinants of response to immunosuppressive therapy with prednisone alone, or prednisone and cyclophosphamide, in IPF. Twenty five consecutive patients were studied. Initial evaluation in untreated patients included clinical, biological and functional parameters. Sequential evaluation by pulmonary function tests (forced vital capacity (FVC) and transfer factor of the lungs for carbon monoxide (TLCO)) was performed at a 3 month interval. Response to therapy was defined as an improvement in FVC and/or TLCO of more than 10% after 12 months, with maintenance of this improvement for at least another 12 months. Twelve of the 25 patients were classified as responders. A symptomatic disease of less than 12 months duration before onset of therapy related to response. FVC was more impaired in the group of responders when the comparison was limited to patients with an FVC of less than 90%. Bronchoalveolar lavage cell counts were not significantly different between responders and non-responders. Assessment of pulmonary function after 3 months of treatment was predictive of maintenance of the response or of even further improvement. Patients with improved FVC after 3 months of therapy had a significantly shorter symptomatic disease before onset of treatment (7.6 +/ 7.1 vs 20.2 +/- 18.6 months). A beneficial effect of addition of cyclophosphamide was observed only in patients who demonstrated an early but short-lived improvement to steroids. Adverse reactions of immunosuppressive therapy were noticed in 10 patients, and required discontinuation of treatment in six of them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875265 TI - No effect of histamine on human bronchial epithelial cell permeability and tight junctional integrity in vitro. AB - Both animal and human studies have suggested that histamine increases airway epithelial cell permeability in vivo. In order to study the effect of histamine on paracellular epithelial permeability and tight junctional integrity, we have cultured human bronchial epithelial cells to confluency and investigated the effect of topically applied 0.1-20.0 microM histamine. Cultures were established on microporous membranes of tissue culture cell inserts and used for the assessment of: 1) transepithelial movement of radiolabelled mannitol (14C mannitol) and bovine serum albumin (14C-BSA), in the luminal to serosal direction and 2) changes in electrical resistance of the cultures. Epithelial cell cultures were also established on plastic coverslips, in order to determine tight junction morphology by freeze-fracture electron microscopy, and to assess junctional integrity by lanthanum penetration, using thin sections. Compared with untreated control cultures, 0.1-10 microM histamine did not significantly alter the movement of either 14C-mannitol or 14C-BSA across the epithelial cultures at any time during incubation, but caused an increase in the electrical resistance of the cultures, which was maximal by 6 h of incubation. The morphology of the tight junctions revealed by freeze-fracture and junctional integrity (the latter determined by the degree of lanthanum penetration) were similar in untreated control cultures and cultures incubated with histamine. These studies indicate that histamine does not have a direct effect on paracellular bronchial epithelial permeability in vitro. PMID- 7875266 TI - Platelet-derived growth factor-beta mRNA in human alveolar macrophages in vivo in asthma. AB - Collagen deposition and myofibroblast proliferation beneath the epithelial basement membrane in patients with asthma is now increasingly recognized, although the molecular pathogenesis remains obscure. We have evaluated messenger ribonucleic acid (mRNA) expression of the profibrotic cytokine, platelet-derived growth factor-beta (PDGF-beta), in alveolar macrophages obtained following fibreoptic bronchoscopy and bronchoalveolar lavage in patients with asthma. Three subject groups were studied: 1) asthmatics using regular inhaled glucocorticoid medication (ASTST, n = 9), 2) asthmatics using intermittent inhaled beta 2 agonist therapy only (ASTBR, n = 10); 3) nonasthmatic control volunteers (n = 10). Alveolar macrophage mRNA was extracted and PDGF-beta mRNA quantified by reverse-transcriptase polymerase chain reaction (PCR) (RT-PCR) and expressed as the ratio to that of a control gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). There were no significant differences in PDGF-beta mRNA expression between the groups, or between all asthmatic (n = 19) and control subjects. Furthermore, there was no correlation between alveolar macrophage PDGF-beta mRNA expression and airway spirometry, or duration of glucocorticoid usage or dose. Thus, in contrast to other fibrotic lung diseases, we found little evidence of enhanced expression of PDGF-beta mRNA in alveolar macrophages in clinically stable bronchial asthma. PMID- 7875267 TI - Bronchoprotection by salmeterol: cell stabilization or functional antagonism? Comparative effects on histamine- and AMP-induced bronchoconstriction. AB - Salmeterol provides bronchoprotection against a number of constrictor stimuli for more than 12 h after a single dose. This effect could be due either to functional antagonism at the level of airway smooth muscle or to cell-stabilizing effects of the compound. In this study, we attempted to clarify this mechanism by comparing the effects of salmeterol (50 micrograms), salbutamol (200 micrograms) and placebo on the airway responsiveness to histamine (to assess functional antagonism), and to adenosine 5'-monophosphate (AMP) (to assess additional cell stabilizing effects), 14 h after drug treatment. Thirteen patients with mild allergic asthma were studied in a double-blind, randomized protocol on 6 days, at least 48 h apart. Forced expiratory volume in one second (FEV1) was measured before and 15 min after inhalation of the study medication. Then, 14 h later (8 a.m. the following morning), a bronchoprovocation test with histamine or AMP was performed. We found that 14 h after inhalation, salmeterol still had a significant effect on FEV1 in comparison to placebo and salbutamol. The provocative dose producing a 20% fall in FEV1 (PD20histamine) was significantly increased after salmeterol, whilst the increase in PD20AMP did not reach significance. The shift in PD20 (in doubling dose steps) induced by salmeterol pretreatment was not different between histamine and AMP. We conclude that the prolonged protective effect of salmeterol occurs via an extended bronchodilating and functional antagonistic action and not via a cell-stabilizing effect. PMID- 7875268 TI - Does single dose salmeterol affect exercise capacity in asthmatic men? AB - The aim of this study was to investigate whether the long-acting beta-agonist salmeterol affects athletic performance in patients with asthma. The effect of 50 micrograms salmeterol on the cardiorespiratory responses to a progressive maximal cycle exercise test and on endurance capacity (defined as the exercise duration at 70% maximum oxygen uptake), was compared with 200 micrograms salbutamol and a matched placebo in eight asthmatic men. Both salmeterol and salbutamol improved pre- and postexercise forced expiratory volume in one second (FEV1) for maximal and endurance exercise. Following active treatment, patients exercised from a significantly high baseline FEV1, with both salmeterol (3.58(1.16)l) (mean (SD)) and salbutamol (3.55(1.24)l) compared with placebo (3.29(1.35)l). Similar improvements preceded endurance exercise. Cardiorespiratory, haemodynamic or subjective responses to the progressive maximum exercise tests were not different with salmeterol, salbutamol or placebo, nor did endurance capacity change with any treatment modality. Blood lactate levels, after 15 min exercise, were significantly higher with salbutamol (3.64 (1.83) mM), but not with salmeterol (3.03 (1.64) mM), compared with placebo (2.95 (1.69) mM). These results demonstrate the absence of significant cardiorespiratory or metabolic effects during exercise after a single dose of salmeterol, together with a lack-of ergogenic effect, as measured by maximal or endurance exercise performance, in patients with asthma. PMID- 7875269 TI - Airways obstruction and two year survival in patients with severe alpha 1 antitrypsin deficiency. AB - Because of the limited number of donor organs available, the selection of patients for lung transplantation is crucial. One important issue in setting priorities is the life expectancy without transplantation. The purpose of this study was to estimate survival based on lung function, in alpha 1-antitrypsin deficient patients. Data from the Danish alpha 1-antitrypsin deficiency registry were analysed. The basic element of the analysis was two year intervals, characterized by date of spirometry and known mortality status 2 yrs later. We found a simple exponential relationship between lung function (forced expiratory volume one second (FEV1)) and two year survival on conservative treatment. The formula implies an almost 100% two year survival until FEV1 falls below one third of predicted normal; at this level two year mortality increases and will reach 50% at a FEV1 of 15% predicted. In conclusion, the two year mortality of emphysema patients due to alpha 1-antitrypsin deficiency increases exponentially with decreasing FEV1 and the results imply that only a few patients who underwent lung transplantation would have had a better two year prognosis without this procedure. PMID- 7875270 TI - Lung volume measurements in wheezy infants: comparison of plethysmography and gas dilution. AB - The accuracy both of plethysmographic measurements of thoracic gas volume (TGV) and determinations of functional residual capacity (FRC) by gas dilution techniques in infants with obstructive lung disease is subject to continued dispute. We studied 25 wheezy infants and compared TGV derived from end expiratory airway occlusions (TGVEE), corrected TGV after end-inspiratory airway occlusions (TGVEI), and FRC determined by nitrogen wash-out (FRCN2). Group mean TGVEE and TGVEI differed significantly (25.8 +/- 8.4 versus 24.6 +/- 7.1 ml.kg 1). TGVEE and FRCN2 did not differ significantly. TGVEE and TGVEI, as well as TGVEE and FRCN2, and TGVEI and FRCN2 data, respectively, showed lack of agreement. Based on 95% confidence intervals, calculated from TGVEE data, 14 of the 25 infants showed a significantly higher TGVEI than TGVEE; only one patient had a significantly lower TGVEI. Compared to FRCN1 data, TGVEE and TGVEI measurements yielded lower values in at least one third of our patients. The present study illustrates, that there is no gold standard for the measurement of lung volume in infants with airway obstruction. PMID- 7875271 TI - Improved detection of abnormal respiratory function using forced expiration from raised lung volume in infants with cystic fibrosis. AB - The raised volume rapid thoracic compression (RVRTC) technique is a recently developed method of measuring lung function in infants. The measurements of forced expiratory volume-time (FEVt) parameters from raised lung volumes have been shown to be less variable than maximal flow at functional residual capacity (VmaxFRC), obtained from the conventional rapid thoracic compression (RTC) technique. Measurements of VmaxFRC are highly variable, and may not be sensitive enough to detect a difference between normal infants and infants with cystic fibrosis (CF). The aim of this study was to determine whether the raised volume rapid thoracic compression technique could detect abnormal lung function in a group of CF infants with no current respiratory symptoms. Twelve CF infants were studied (median age 10.5 months, range 3-18 months), and compared to normative data collected previously on 26 healthy infants (median age 14 months, range 3-23 months). We found that VmaxFRC failed to detect any difference between the two groups. CF infants had significantly smaller FEV0.5 and FEV0.75 measurements at a lung volume set by 17.5 cmH2O predetermined inflation pressure (PP) both as raw values and when expressed as percentage predicted. We conclude that the raised volume rapid thoracic compression technique is a sensitive tool, able to detect abnormal lung function in infants with cystic fibrosis. This abnormality was not demonstrated by measurements derived from the conventional rapid thoracic compression technique in the tidal volume range. PMID- 7875272 TI - Changes in respiratory resistance to low dose carbachol inhalation and to pneumatic trouser inflation are correlated. AB - Inflation of the leg compartments of pneumatic trousers increases thoracic blood volume. The resultant response in respiratory impedence was investigated in nine normal volunteers, and compared with the response to increasing doses of inhaled carbachol. Respiratory impedance was measured by the forced oscillation technique (4-32 Hz), and respiratory resistance at zero frequency (R0) was extrapolated from linear regression analysis of resistive impedance versus frequency. The mean increase in R0 was 31% after inhalation of 125 micrograms carbachol, and 21% after inflation of pneumatic trousers. The percentage changes in R0 following pneumatic trouser inflation highly correlated those induced by inhalation of 125 micrograms carbachol (r = 0.98) Our data demonstrate that, even in normal subjects, pneumatic trouser inflation causes an increase in respiratory resistance, which can be predicted by the response to a low dose of carbachol. These results support the assumption that cholinergic agents might not only be bronchoconstrictors but also vasodilators of the bronchial vessels. At a low dose, the vasodilating action of carbachol could be the major factor involved in the respiratory response. PMID- 7875273 TI - Effect of nasal CPAP on ventilatory drive in normocapnic and hypercapnic patients with obstructive sleep apnoea syndrome. AB - The purpose of this study was to evaluate the effect of nasal continuous positive airway pressure (CPAP) on the abnormal ventilatory drive in hypercapnic patients with the obstructive sleep apnoea syndrome (OSAS). Six patients with hypercapnic OSAS (Group I) and 24 patients with eucapnic OSAS (Group II) were studied. All patients had arterial blood gas analysis, overnight sleep studies, and an assessment of ventilatory drive (progressive hyperoxic hypercapnic response and progressive isocapnic hypoxic ventilatory response) prior to and during nasal CPAP therapy (at 2 weeks and 1 month of treatment). Nasal CPAP effectively improved the hypopnoea/apnoea index in both groups (Group I: 87 +/- 14 vs 8 +/- 4; Group II: 63 +/- 17 vs 6 +/- 3). Both hypercapnic and hypoxic ventilatory drive before treatment were significantly impaired in Group I as compared to Group II. Both the slope and baseline level of the ventilatory response and the mouth occlusion pressure (P0.1) improved significantly after 2 weeks of nasal CPAP therapy in Group I, with normalization of arterial carbon dioxide tension (PaCO2) (6.3 +/- 0.2 to 5.2 +/- 0.4 kPa). We conclude that it is possible to completely correct the abnormal ventilatory drive in hypercapnic OSAS patients within 14 days of initiating nasal CPAP therapy. PMID- 7875274 TI - Nitrazepam in patients with sleep apnoea: a double-blind placebo-controlled study. AB - We wanted to assess whether benzodiazepines worsen sleep apnoea, since their use in such patients has been controversial. Fourteen male patients with mild to moderate obstructive sleep apnoea were investigated in a placebo-controlled, double-blind study evaluating the influence of nitrazepam (NIT) on apnoea frequency and severity. Each patient was given oral nitrazepam 5 or 10 mg, or corresponding placebo, in a randomized order on three separate nights. Wash-out time was one week. A complete sleep study was undertaken at each study night. Eleven patients completed the study. Although there were individuals with marked variability in apnoea index between the three study nights, there was no significant change in apnoea index or minimum arterial oxygen saturation with any of the two nitrazepam dosages studied. Only 3 out of 11 patients had a higher apnoea index after both nitrazepam doses compared to placebo, and in these patients the increase in sleep-disordered breathing was of marginal clinical significance. Nitrazepam caused a modest increase in total sleep time and a decrease in rapid eye movement (REM) sleep. These results demonstrate that nitrazepam does not worsen sleep apnoea in patients with mild to moderate sleep apnoea. The previously reported sleep apnoea promoting effects of benzodiazepines may be restricted to a small subgroup of patients with sleep-disordered breathing. PMID- 7875275 TI - Comparison of oxygen uptake during a conventional treadmill test and the shuttle walking test in chronic airflow limitation. AB - The purpose of this study was to investigate the relationship between performance on the shuttle walking test and maximal oxygen uptake (VO2max) during a conventional treadmill test in patients with chronic airflow limitation. Two different techniques were used to measure oxygen consumption, i.e. conventional Douglas bag techniques (treadmill test) and a portable oxygen consumption meter (shuttle test). Initially, 19 patients performed a shuttle walking test (after one practice walk) and a maximal treadmill walking test, in a randomized, balanced design. Subsequently, 10 patients, (after one practice) completed an unencumbered shuttle walking test and one supporting the portable oxygen consumption meter, in random order. The results of the first experiment revealed a strong relationship between performance during the shuttle walking test and VO2max during the treadmill walking test (r = 0.88). The results of the second experiment consistently demonstrated an incremental increase in oxygen consumption and ventilation in response to the increasing intensity of the shuttle walking test. Again, a strong relationship between VO2max and performance on the shuttle test was demonstrated (r = 0.81). We concluded that the shuttle walking test is a valid field exercise test of functional capacity. Performance on the test relates strongly to VO2max, the traditional indicator of cardiorespiratory capacity. PMID- 7875276 TI - Survey on domiciliary oxygen by concentrator in England and Wales. AB - Long-term oxygen therapy is initiated in England and Wales by the patient's family doctor, sometimes at the request of a hospital consultant. Guidelines for therapy exist but are not mandatory. We wish to investigate the numbers and types of patients being treated under this regimen, the method of treatment and how they responded to their oxygen dose. We therefore interviewed and tested patients at the inception of therapy in six of the nine prescribing areas of the whole country, during August 1990 and February 1991. Main outcome measures were diagnoses, daily duration and flow prescribed, arterial oxygen saturation (SaO2) breathing air and improvement in arterial oxygen saturation on prescribed oxygen. Most patients both in summer and winter reported diagnoses of chronic bronchitis (45%) or emphysema (50%), in addition to other conditions. Most were male (58%), and most (72%) were over retirement age. Roughly half (45%) were house-bound, but only 28 (6%) were totally bedridden. Three quarters (77%) reported that a hospital consultant had told them how much oxygen to use, and in all diagnostic groups mean prescriptions exceeded 15 h.day-1 and 2 l.min-1. However, only half (54%) of the patients with complete measurements had basal arterial oxygen saturation of 90% or less at the start of treatment, together with a satisfactory improvement in arterial oxygen saturation on the prescribed flow of oxygen. In conclusion, patients are usually prescribed adequate regimens but little attempt is made to ensure that prescription is appropriate or response satisfactory. Resources continue to be used for treating patients without ensuring that they benefit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875277 TI - Hygroscopic condenser humidifiers in chronically tracheostomized patients who breathe spontaneously. AB - The aim of this study was to test the usefulness of hygroscopic condenser humidifiers on secretion and on inspired gas temperature in tracheostomized patients. Forty spontaneously breathing chronically tracheostomized patients were divided into two groups: Group 1 received a hygroscopic condenser humidifier connected to the tracheostomy, 24 h daily for 10 days; Group 2, without any protection system, was chosen as the control group. The daily number of tracheal suctions, quantity of aspirate and thickness and colouring of secretions was evaluated. At baseline, and at days 5 and 10, patients were submitted to blood gas analysis, respiratory function tests and sputum analysis. The temperature of gases breathed was measured at rest and during a hyperventilation test, with and without the hygroscopic condenser humidifier. Statistically significant differences were found in thickness and colouring of secretions between the two groups during the period of 10 days. Group 2 showed a significantly greater trend in number of bacteria than Group 1. The group with the hygroscopic condenser humidifier showed respiratory function improvement over time for forced expiratory volume in one second (FEV1) and tidal volume (VT), maximal inspiratory pressure (MIP), and maximal voluntary ventilation (MVV) in comparison to the control group, who did not. Significant differences in the temperature between rest and hyperventilation, with and without a hygroscopic condenser humidifier were also found. In conclusion, a hygroscopic condenser humidifier may be useful in chronically tracheostomized patients who breathe spontaneously, improving viscosity and colouring of secretions, preventing further bacterial colonization, heating inspiratory flow, and helping to improve the functional outcome. PMID- 7875278 TI - Three years experience with a new balloon catheter for the management of haemoptysis. AB - For the management of severe haemoptysis we have developed a double-lumen, bronchus-blocking catheter that can be introduced through the working channel of a standard fibrebronchoscope. We wondered whether this catheter would be suitable to control pulmonary haemorrhage in clinical practice. Over a period of 36 months, 30 of these catheters were used in 27 patients with moderate and massive pulmonary bleeding from various lesions. Underlying diseases were: malignancies (11), vascular deformities (5), tuberculosis (4), silicosis (2), carcinoids (2), silicosis (2), endometriosis (1), bronchiectasis (1). In 26 cases, the transbronchoscopic balloon tamponade was successful. In one patient, tumour growth close to the carina prevented securing of the balloon and double-lumen tube intubation was required. There were only minor complications attributable to the balloon. With the catheter in place for up to seven days, patients underwent surgery, received radiation, chemotherapy, drug treatment or bronchial arterial embolization. In conclusion, we found this double-lumen, bronchus-blocking device safe and the technique practicable to control pulmonary haemorrhage. PMID- 7875279 TI - Theoretical and experimental basis for the development of a dynamic airway stent. AB - Three major problems are currently associated with airway stents: mucostasis, formation of granulation tissue, and migration. We wanted to determine whether these problems could be solved by a different stent design. Based on theoretical considerations of an idealized trachea, we developed a dynamic bifurcation stent made of silicone which incorporates horseshoe-shaped steel struts. A flexible posterior membrane enables dynamic compression during cough, whilst the clasps maintain the airway lumen in the face of external compression. The design of the stent cast was based upon computed tomographic (CT)-scan studies of the central airways. Its complex shape provides a smoother distribution of pressure on the mucosa; thereby, lowering the stimulus for granulation formation. The bronchial limbs saddle on the carina, preventing displacement. The mechanical behaviours of the new stent and two commercially available stents were compared in an ex-vivo model, utilizing freshly excised tracheae and new visualization techniques. Dynamic (artificial coughs) and static loads (simulating tumour compression or pleural pressures) were applied on excised human tracheae with different stents. Our dynamic stent preserved effective compression of the posterior membrane in response to cough, and also provided lumen stability against extrinsic compression. In comparison, the two commercially available stents did not provide both functions equally well. In conclusion, our newly designed dynamic bifurcation stent shows characteristics which should prove useful in avoiding problems currently associated with airway stents. PMID- 7875280 TI - Prevalence of asthma and wheeze in Hong Kong schoolchildren: an international comparative study. AB - Comparison of asthma prevalence between populations is difficult because of lack of uniformity of methodology and agreement on the definition. This study aims to determine and compare the prevalence of wheeze and respiratory symptoms in Hong Kong schoolchildren with that in Melbourne children by using identical questionnaires. Schools were randomly selected in different regions of Hong Kong and three age groups (7, 12 and 15 yrs) were chosen for the study. The Chinese version of the questionnaire used in a recent Melbourne survey was distributed to children for completion by their parents. A total of 1,800 questionnaires was issued and 1,689 returned (response rate = 94%). The prevalence of wheeze in the past 12 months was 7 (5.1-8.0), 5 (3.0-6.7) and 4 (1.7-5.6) % for 7, 12 and 15 year olds, respectively. The prevalence of a history of asthma in the respective age groups was 10 (7.1-12.9), 8 (7.5-9.2) and 7 (5.0-9.6) %, respectively. Whilst a history of wheeze ever was more common in boys than in girls and 12 yr olds (14% vs 5%), wheeze in the past 12 months was more common in boys than in girls aged 7 yrs (9 vs 4%). We conclude that the prevalence of wheeze and asthma in school children was low in Hong Kong compared to Melbourne. Environmental differences between the two regions may be important in the pathogenesis. PMID- 7875281 TI - Protocols for in vivo measurement of the ion transport defects in cystic fibrosis nasal epithelium. AB - New treatments for cystic fibrosis (CF), including gene therapy, are currently being assessed. These aim to correct the basic defects of increased sodium absorption and decreased chloride secretion in airway epithelia. Assessment of these bioelectric parameters, particularly in the nasal epithelium, is likely to be used as a measure of treatment efficacy. However, the optimal in vivo protocol to discriminate cystic fibrosis from non-cystic fibrosis subjects is unclear. We have, therefore, compared three protocols for measurement of the cystic fibrosis ion transport defects in vivo in the nasal epithelium. Sodium absorption was measured using both the baseline potential difference and the response to the sodium channel blocker, amiloride. Chloride secretion was assessed in the presence of amiloride, using perfusion with isoprenaline, or terbutaline, or a low chloride solution followed by isoprenaline. Baseline potential difference (PD) and the absolute response to amiloride clearly differentiated the increased sodium absorption in the cystic fibrosis subjects. The responses both to terbutaline (delta PD: non-CF: -0.8 (SEM 0.7) mV; CF: -3.6 (0.5) mV) and isoprenaline (non-CF: 1.5 (0.6) mV; CF: -2.9 (0.6) mV) differentiated the two groups of subjects, but there was considerable overlap of values. Perfusion with a low chloride solution (non-CF: 12.6 (1.2) mV; CF: 0.6 (0.4) mV), as well as subsequent perfusion with isoprenaline (non-CF: 10.0 (1.1) mV; CF: -1.4 (0.4) mV) allowed clear separation of the two groups, with no overlap of values. Some CF subjects showed a transient hyperpolarization to these stimuli, which could clearly be differentiated from the sustained responses seen in non-cystic fibrosis subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875282 TI - Assessment of respiratory muscle strength in the intensive care unit. AB - The measurement of respiratory muscle strength in the intensive care unit (ICU) is potentially useful for the prediction of weaning outcome. An easy and accurate measure would also allow investigation of respiratory muscle weakness in critically ill patients. At present, there is no satisfactory method of strength measurement in the intensive care unit. Vital capacity is a nonspecific, volitional and relatively insensitive measure of strength. True maximum respiratory pressures are difficult to achieve and, in stable patients, results vary greatly both over time and between observers. For these reasons, there are few good data of respiratory muscle strength in the intensive care unit. Of the new techniques being developed, magnetic stimulation of the phrenic nerves, combined with the measurement of transdiaphragmatic, oesophageal, or endotracheal tube pressure, offers the greatest promise. PMID- 7875283 TI - Evaluation of three different techniques used to measure chest wall movements in children. AB - Several techniques exist for assessing chest wall movements in children, that incorporate different measurement principles. Although the output from such devices appears very similar, the comparability of data from different devices needs to be evaluated. We have investigated the simultaneous measurement of chest wall movement using three different devices in 12 children recovering from intensive care. The devices used were inductance plethysmography (assessing thoracic cross-sectional area), magnetometers (assessing thoracic diameter), and a Hall device strain guage (assessing thoracic circumference). Measurements of respiratory timing and of phase angle between rib cage and abdomen in these patients showed a close agreement between devices in ventilated patients. However, occasional inconsistencies occurred in patients who were breathing spontaneously. We suggest that it may not always be appropriate to directly compare data on chest wall movements in children recorded using different measurement techniques. The best method of measurement varies with the clinical picture. PMID- 7875284 TI - Do turbines with servo-controlled speed improve continuous positive airway pressure generation? AB - Nasal continuous positive airway pressure (CPAP) devices with a servo-mechanism to control pressure have recently been developed. We evaluated six such devices and three conventional systems in terms of effectiveness in maintaining constant pressure. Machines were tested with pressure levels of 5, 10 and 15 cmH2O. Dynamic behaviour was evaluated: 1) by calculating the imposed work of breathing during simulated breath generated by a sinusoidal pump; and 2) by following the fall in pressure after a transient flow of 1 l.s-1. Quasi-static behaviour was evaluated by simulating a predetermined air leak. Under dynamic conditions, work of breathing was lowest with one conventional nasal CPAP device and three servo controlled nasal CPAP devices; whereas, the highest levels of work of breathing were recorded with two servo-controlled nasal CPAP devices. The pressure-time response to a transient flow yielded similar results, with a significant inverse correlation between pressure values observed after 300 ms and imposed work of breathing during simulated breathing (r = -0.91). Under quasi-static conditions, microprocessor servo-controlled devices exhibited the best performance. These results suggest that microprocessor servo-controlled nasal CPAP devices are not always the best systems for maintaining constant airway pressure in dynamic situations. However, they are more effective in ensuring maintenance of the desired pressure in the event of an air leak at the mask. PMID- 7875285 TI - Platypnoea syndrome caused by atrial septal aneurysm. AB - A patient with platypnoea after right pneumonectomy and radiotherapy is described. On transoesophageal contrast echocardiography and cardiac catheterization, an atrial septal aneurysm with interatrial right-to-left shunting was detected. Symptoms disappeared after surgical correction. To the best of our knowledge, this is the first report of a patient with a septal aneurysm and severe platypnoea. PMID- 7875286 TI - Attenuation of hypoxic ventilatory response after recovery from chronic hypoxaemia in a case of pulmonary A-V fistula. AB - We studied respiratory chemosensitivity in a patient with pulmonary arterio venous (AV) fistulae before and after surgical removal of the lesions. The patient had had moderate hypoxaemia with hyperventilation before the operation. When first studied, 21 days following surgery, both hypoxic and hypercapnic ventilatory responses were found to be lower than they were preoperatively. During the next 1-2 months, hypoxic ventilatory response continued to fall significantly to a steady value, whereas hypercapnic response showed no further fall. There has been no previous report of such a phenomenon in humans after recovery from chronic hypoxaemia. PMID- 7875287 TI - Salmeterol-induced vertigo. AB - Dizziness, together with hypotension and faintness, are well-known adverse drug reactions of salbutamol that have been related to its cardiovascular effects. However, we could find no published reference to vertigo in patients taking salmeterol, in the absence of cardiovascular alterations. We present the case of a woman who experienced four independent episodes of vertigo lasting 36 h each, following four inhalations of salmeterol several months apart. The close temporal relationship between the inhalation of salmeterol and the onset of symptoms, as well as the positive re-exposures, reinforce this alleged association. PMID- 7875288 TI - Herpes simplex virus tracheitis in a patient with the acquired immunodeficiency syndrome. AB - Herpetic tracheobronchitis and pneumonia occur basically in immunodepressed patients, but have rarely been reported in patients with the acquired immunodeficiency syndrome (AIDS). Some large reviews on pulmonary manifestations in AIDS report a small number of herpetic pulmonary infections, without determining any prevalence of this particular viral involvement. Predisposing factors are alteration of cell-mediated immunity and invasive procedures (such as endotracheal tube use) in debilitated patients. The case we report illustrates the occurrence of a herpetic tracheitis in an HIV-infected patient with severe P. carinii pneumonia, needing systemic corticotherapy and mechanical ventilation. It illustrates the risk of dissemination of herpes simplex virus (HSV) from a herpetic stomatitis to the lower respiratory tract, even after the endotracheal cannula has been removed. PMID- 7875289 TI - A persistent unilateral lung infiltrate. AB - We describe the case of an intrabronchial aspirated foreign body that caused a persistent right lower lobe infiltrate. A first fibreoptic bronchoscopy demonstrated a mass with tumour-like appearance in the right bronchus intermedias, but the bronchial biopsies and the cytological smears of the bronchial aspirate failed to reveal any malignancy. During a control fibreoptic bronchoscopy, we found a chicken bone in this friable granulation tissue. It was subsequently removed with a flexible bronchofibrescope and a four-pronged forceps under topical anaesthesia. PMID- 7875290 TI - Chronic eosinophilic pneumonia (CEP) as a presenting feature of Churg-Strauss syndrome (CSS). PMID- 7875291 TI - Enzymatic activity of a developmentally regulated member of the sialyltransferase family (STX): evidence for alpha 2,8-sialyltransferase activity toward N-linked oligosaccharides. AB - We have detected sialyltransferase activity of recombinant mouse STX, which was cloned from rat brain as a new member of the sialyltransferase family, but sialyltransferase activity of which had not been detected previously [Livingston and Paulson, J. Biol. Chem. (1993) 268, 11504-11507]. The activity of mouse STX was specific toward sialylated glycoproteins. N-Glycanase treatment and linkage specific sialidase treatment of glycoproteins revealed that STX transfers sialic acids through alpha 2,8-linkages to only N-linked oligosaccharides of glycoproteins. However, polymerase activity for polysialic acid synthesis was not detected for this sialyltransferase. Since this alpha 2,8-sialyltransferase gene is highly restricted in fetal and newborn brain, it may be involved in the polysialylation of glycoproteins, especially of N-CAM. PMID- 7875292 TI - Multiple isoforms of Pisum trypsin inhibitors result from modification of two primary gene products. AB - Characterization of Pisum (pea) seed trypsin inhibitors (TI) and their corresponding cDNAs indicates that the pea TI gene family contains two genes. The existence of multiple TI isoforms can be attributed to post-translational modifications of primary gene products. Post-translational processing at the C terminus during the desiccation stage of seed development results in the appearance of TI isoforms with increased affinity for the target enzyme, trypsin. PMID- 7875293 TI - Extension of DNA triple helix formation to a neighbouring (AT)n site. AB - We have used DNase I footprinting to examine the formation of intermolecular triple helices at a fragment containing the target sequence A11(AT)6.(AT)6T11, using oligonucleotides designed to form parallel T.AT and G.TA triplets. We find that, although (TG)6 does not form a complex with (AT)6.(AT)6, T11(TG)6 forms a stable structure producing a clear footprint which includes the (AT)6 portion of the target site. This complex is not formed in the presence of magnesium, but can be stabilised by either manganese or a triplex-binding ligand. PMID- 7875294 TI - A critical mutation in both WT1 alleles is not sufficient to cause Wilms' tumor. AB - The WT1 gene is a tumor suppressor gene for Wilms' tumor (WT). Inactivation of both alleles has been proposed as the cause of WT. We encountered a patient with Denys-Drash syndrome associated with WT whose WT1 gene had a homozygous point mutation not only in WT but also in renal tissue adjacent to the WT and in the germline. These findings indicate that factor(s) other than the loss of WT1 are required for WT to develop. PMID- 7875296 TI - The cation-independent mannose-6-phosphate receptor binds to soluble GPI-linked proteins via mannose-6-phosphate. AB - The cation-independent mannose-6-phosphate/insulin-like growth factor II receptor has been observed to bind to soluble forms of glycosyl-phosphatidylinositol linked molecules, one of mammalian origin (rat Thy-1) and two of protozoan origins. Of the two phosphate groups found on the soluble forms of the protozoan glycosyl-phosphatidylinositol-linked molecules: (i) the internal mannose-6 phosphate diester (which forms a part of the ethanolamine bridge) and (ii) the inositol-1,2 cyclic phosphate group (which arises after cleavage of the membrane associated form with phosphatidylinositol-specific phospholipase C), only the former appears to be recognized by the mannose-6-phosphate/insulin-like growth factor II receptor, as mild acid hydrolysis which destroys the latter has been observed not to affect the receptor binding site. PMID- 7875295 TI - Colony-stimulating factors and interferon-gamma activate a protein related to MGF Stat 5 to cause formation of the differentiation-induced factor in myeloid cells. AB - The Jak-Stat pathway of intracellular signals is used by growth factor- and cytokine receptors to induce gene transcription. We have recently reported that differentiation of myeloid cells, induced by phorbol ester, interferon-gamma (IFN gamma) or colony-stimulating factor-1 (CSF-1) is accompanied by the activation of the differentiation-induced factor (DIF). Activated DIF specifically associates with a subclass of gamma-interferon activation site (GAS)-like DNA elements. We now report that GM-CSF, which like CSF-1 promotes the generation of mature macrophages, activates DIF. No activation was observed after treatment with the granulocyte growth and differentiation factor G-CSF. Antibodies raised against a Stat family protein, designated mammary gland factor-Stat 5 (MGF-Stat 5), reacted with DIF induced by either CSF-1, GM-CSF or IFN-gamma. Antisera to other known Stats were without effect on the DIF complex in electrophoretic mobility shift assays (EMSA). A 112 kDa protein could be isolated from either GM-CSF- or IFN gamma-treated cells by GAS oligonucleotide precipitation. This protein reacted with antibodies to both MGF-Stat 5 and phosphotyrosine. MGF-Stat 5 and closely related proteins thus define a subfamily of Stat transcription factors that are present in a variety of cell types and are required for the onset of immediate gene expression in response to differentiating stimuli. PMID- 7875297 TI - Regulation of cytochrome c expression in the aerobic respiratory yeast Kluyveromyces lactis. AB - Transcriptional regulation of the KlCYC1 gene from the aerobic respiratory yeast Kluyveromyces lactis has been studied. The KlCYC1 gene produces two transcripts of different sizes, in contrast with the single transcripts found for CYC1 and CYC7 from Saccharomyces cerevisiae, and for the CYC gene from Schwanniomyces occidentalis. Both KlCYC1 transcripts respond in the same way to the regulatory signals studied here. The transcription of KlCYC1 is regulated by oxygen and this control is mediated by heme. The KlCYC1 gene is also subject to catabolite repression. Heterologous expression in S. cerevisiae mutants reveals that the factors HAP1 and HAP2 take part in the regulatory mechanism. PMID- 7875298 TI - The membrane distal half of gp130 is responsible for the formation of a ternary complex with IL-6 and the IL-6 receptor. AB - Gp130 is the signal transducing subunit of the interleukin-6 receptor. Signaling is initiated by the complex formation of gp130 with IL-6 bound to the IL-6 receptor (IL-6R). We have subdivided the extracellular domain of gp130 in two parts and expressed the mutant proteins as soluble IgG fusion proteins in COS-7 cells. By studying the formation of the ternary complex we show that the membrane distal half of gp130 which contains a cytokine receptor domain is responsible for the interaction with the IL-6/IL-6R complex. Interestingly this is the same region which is believed to be involved in specific recognition of the related cytokines LIF, OM, and probably also of CNTF and IL-11. PMID- 7875299 TI - Photosensitized decomposition of S-nitrosothiols and 2-methyl-2-nitrosopropane. Possible use for site-directed nitric oxide production. AB - Irradiation of S-nitrosoglutathione (GSNO) with light (lambda = 550 nm) resulted in the homolytic decomposition of GSNO to generate glutathionyl radical (GS.) and nitric oxide (.NO), which were monitored by ESR spectrometry. Inclusion of Rose Bengal (RB) resulted in a 9-fold increase in the quantum yield for .NO production and also an increase in the rate of thiyl radical formation. The bimolecular rate constant for the interaction of triplet RB with GSNO has been estimated to be approximately 1.2 x 10(9) M-1s-1 by competition with oxygen. Hematoporphyrin (HP) also enhanced the rate of .NO production by 2-3-fold. 2-Methyl-2-nitrosopropane (MNP) decomposed on irradiation (lambda = 660 nm) to form .NO and tert-butyl radical. Aluminum phthalocyanine tetrasulphonate enhanced the rate of decomposition of MNP by 10-fold. These studies show that photosensitizers enhance the release of .NO from donor compounds. PMID- 7875301 TI - Synthesis and refolding of human TIMP-2 from E. coli, with specific activity for MMP-2. AB - Tissue inhibitors of metalloproteinase (TIMPs) are inhibitory counterparts of collagenases, containing 12 cysteine residues paired to six internal disulphide bridges. TIMP-2, an inhibitory protein of 72 kDa gelatinase/type IV collagenase (MMP-2), was expressed in Escherichia coli as a fusion protein with a 34 amino acid NH2-linked tail containing six consecutive histidine residues. The protein was purified in a single-step using an ion metal affinity column (IMAC) in denaturing conditions. The immobilized fusion TIMP-2 protein was refolded at a high concentration in the column, producing about 5 mg of protein per litre of bacterial cells. It shows specific binding and inhibitory activity against MMP-2, but has no effect against 92 and 45 kDa gelatinases. PMID- 7875300 TI - Abnormally phosphorylated tau in SY5Y human neuroblastoma cells. AB - In Alzheimer disease (AD) the microtubule associated protein (MAP) tau is hyperphosphorylated at several sites. In the present study, like AD tau, tau in the human neuroblastoma SH-SY5Y was found to be hyperphosphorylated, at Ser 199/202, Thr-231, Ser-396 and Ser-404. However, in contrast to AD, the tau in SY5Y cells was not hyperphosphorylated at Ser-235 and there was only one tau isoform. Quantitative analysis revealed that approximately 80% of the SY5Y-tau was phosphorylated at Ser-199/202. The phosphorylated tau was deposited in perikarya and processes of the cells whereas most of the unphosphorylated (at Ser 199/202) tau was localized in the nucleus. Tau from the cell lysates did not bind to taxol-stabilized microtubules. In contrast, MAP1b and MAP2 from cell lysates bound to stabilized microtubules in vitro and were associated to the microtubule network in situ. Phosphorylation of tau at high levels, its inactivity with microtubules and its accumulation in SY5Y cells provide for the first time a cell model of cytoskeletal changes seen in AD. PMID- 7875302 TI - Changes in protein methylation associated with the elicitation response in cell cultures of alfalfa (Medicago sativa L.). AB - The methylation of endogenous proteins increased in alfalfa cell suspension cultures following treatment with a fungal elicitor. Carboxyl methylation, a post translational modification associated with controlling the localisation and longevity of proteins, was the dominant form of protein methylation in both elicited and unelicited cells. Protein methylation was restricted to a limited number of peptides prior to elicitor treatment but as elicitation progressed the number of endogenous substrates increased. Increases resulted from a combination of an elicitor-dependent increase in the activity of a protein carboxyl methyltransferase and the accumulation of preferred endogenous substrates in the latter stages of elicitation. PMID- 7875303 TI - The potent mitogen Pasteurella multocida toxin is highly resistant to proteolysis but becomes susceptible at lysosomal pH. AB - The susceptibility of the potent mitogen Pasteurella multocida toxin (PMT) to various proteases was investigated. PMT at a toxin to protease molar ratio of 1:1 was resistant to 8 of the 11 proteases tested after one hour. With longer incubation, PMT remained resistant to 7 proteases, and this correlated with a retention of biological activity, indicating that PMT might not require proteolytic cleavage at least until it bound to a cell receptor. Previous evidence had suggested that PMT is processed in the cell via an endosome or lysosome. We have shown that PMT became susceptible to proteolysis when the pH was lowered to 5 or below. This supports the previous suggestion that PMT is processed via a low pH compartment in the cell. PMID- 7875304 TI - Modulation of the levels of ouabain-like compound by central catecholamine neurons in rats. AB - Catecholamine regulates the Na+,K(+)-ATPase activity in the central nervous system and the Na+,K(+)-ATPase has been shown to have endogenous ligands (ouabain like compound; OLC). To examine the relationship between OLC and central adrenergic neurons, we evaluated the effects of central sympathectomies with intracerebroventricular (i.c.v.) injection of 6-hydroxydopamine (6-OHDA; 250 micrograms) on brain and plasma OLC levels and brain catecholamine levels. In centrally sympathectomized rats, hypothalamic OLC content and plasma OLC level were significantly decreased by 90% (P < 0.01) and 70% (P < 0.01), respectively, in accordance with reduced brain norepinephrine content compared with control rats pretreated by i.c.v. injection of vehicle (ascorbic acid). On the other hand, peripheral sympathectomy with a similar manner did not affect plasma OLC level at all. These findings suggest that central adrenergic neurons may be involved in the synthesis and/or release of circulating OLC. PMID- 7875305 TI - Cyclooxygenase inhibitors augment the production of pro-matrix metalloproteinase 9 (progelatinase B) in rabbit articular chondrocytes. AB - Matrix metalloproteinase 9 (MMP-9/gelatinase B) has recently been proposed to participate in the destruction of articular cartilage. Here, we report that interleukin 1 (IL-1) enhances the production of the precursor of MMP-9 in rabbit articular chondrocytes in primary culture, and this IL-1-mediated production of proMMP-9 is greatly augmented by cyclooxygenase inhibitors such as diclofenac and indomethacin, whereas the constitutive production of proMMP-2 (progelatinase A) is not modulated by IL-1 and/or cyclooxygenase inhibitors. Exogenous prostaglandin (PG) E1 and PGE2 suppress the proMMP-9 production in a dose dependent manner. Similar results are also obtained with cultured rabbit synoviocytes. These results provide the first evidence that PGE down-regulates the production of proMMP-9 in chondrocytes and synoviocytes. Thus, cyclooxygenase inhibitors probably exert undesirable catabolic actions on the maintenance of articular cartilage under inflammatory conditions. PMID- 7875306 TI - Characterization and ultrastructural localization of annexin VI from mitochondria. AB - Annexin VI, a member of a family of related intracellular proteins that associate reversibly with membrane phospholipids in a Ca(2+)-dependent manner, has been purified from bovine liver mitochondria and characterized. Moreover, biochemical and immunocytochemical lines of evidence are presented which strongly suggest that annexin VI is closely associated with the cristae in the inner membrane of mitochondria. These findings are consistent with a calcium channel activity of annexin VI in mitochondria. PMID- 7875307 TI - The non-steroidal anti-inflammatory drug, indomethacin, as an inhibitor of HIV replication. AB - Indomethacin, a common non-steroidal anti-inflammatory drug (NSAID), has been used to treat rheumatoid arthritis. Although indomethacin has also been used as an immunopotentiator and symptomatic NSAID in AIDS, its effect on HIV replication is unknown. MT-4 lymphocytes were inoculated with HIV in the presence of indomethacin and tested for p24 expression by ELISA. The 50% inhibition (IC50) was 10 microM, corresponding to plasma levels after administration of 50 mg oral indomethacin. The antiviral effect appears to be specific since no toxicity has been observed at the IC50 dose, and unrelated NSAIDs have not shown the activity at clinical doses. Indomethacin may, thus, represent a new class of anti-HIV drug. PMID- 7875309 TI - The use of electrospray mass spectrometry to identify an essential arginine residue in type II dehydroquinases. AB - The arginine-specific reagent phenylglyoxal has been used to identify a hyper reactive arginine residue which is essential for activity in the type II dehydroquinases of Streptomyces coelicolor and Aspergillus nidulans. Electrospray mass spectrometry was used both to characterise the phenylglyoxal modified protein, and to identify the phenylglyoxal modified peptides following enzymatic digestion. The advantages of using electrospray mass spectrometry for monitoring arginine modication aimed at identifying functional residues in proteins are discussed. PMID- 7875308 TI - Interaction of smooth muscle caldesmon with calmodulin mutants. AB - The interaction of avian smooth muscle caldesmon with calmodulin (CaM) was investigated by studying the ability of selected mutant calmodulins to induce fluorescence changes in caldesmon. Different types of CaM mutants were used including point charge mutants, cluster mutations, and mutations which alter the calcium binding of CaM. The caldesmon binding properties were only slightly affected by E84K-CaM or by the double mutation E84Q/E120Q-CaM. Affinity of calmodulin to caldesmon was decreased 2-4 times by point mutation G33V-CaM, double mutation E84K/E120K-CaM, deletion of residues 82-84, and by cluster mutations DEE118-120-->KKK or EEE82-84-->KKK. Mutations of the first (E31A-CaM) and the second (E67A-CaM) calcium binding sites reduced the affinity of calmodulin to caldesmon by at least 5-fold; in addition these calmodulin mutants exhibited smaller changes in the fluorescence spectra of caldesmon. Simultaneous mutation of the two negatively charged clusters of calmodulin EEE82-84-->KKK and DEE118-120-->KKK resulted in a more than 15-fold decrease in the affinity of calmodulin for caldesmon. The data indicate that charged and uncharged amino acids in both halves of CaM play an important role in the binding of calmodulin to caldesmon, and that Ca2+ binding must be maintained in the amino-terminal sites for maximal interaction with caldesmon. PMID- 7875310 TI - Gz coupling to the rat kappa-opioid receptor. AB - We have expressed the cloned rat kappa-opioid receptor in human embryonic kidney 293 cells and studied the ability of kappa-selective ligands to inhibit adenylyl cyclase. In transfected 293 cells, activation of the kappa-opioid receptor by U50,488 and the dynorphins resulted in the inhibition of cAMP accumulation. The inhibitory response was sensitive to pertussis toxin and highly selective for kappa-agonists; neither mu- nor delta-opioids were able to activate the kappa opioid receptor. Upon co-transfection with the alpha subunit of Gz, inhibition of cAMP accumulation by kappa-agonist became refractory to pertussis toxin, indicating that the kappa-opioid receptor can couple to both G(i) and Gz proteins. PMID- 7875311 TI - Identification of bovine stefin A, a novel protein inhibitor of cysteine proteinases. AB - For the first time, three different stefins, A, B and C, have been isolated from a single species. The complete amino acid sequence of bovine stefin A was determined. The inhibitor, with a calculated M(r) of 11,123, consists of 98 amino acid residues. Although it exhibits considerable similarity to human and rat stefin A, some significant differences in inhibition kinetics were found. Bovine stefin A bound tightly and rapidly to cathepsin L (kass = 9.6 x 10(6) M-1.s-1, Ki = 29 pM). The binding to cathepsin H was also rapid (kass = 2.1 x 10(6) M-1.s-1), but weaker (Ki = 0.4 nM) due to a higher dissociation rate constant. In contrast, the binding to cathepsin B was much slower (kass = 1.4 x 10(5) M-1.s-1), but still tight (Ki = 1.9 nM). PMID- 7875313 TI - An exact mathematical expression for describing competitive binding of two different ligands to a protein molecule. AB - The dissociation constant for the binding of a spectroscopically invisible or non radioactive ligand to its protein receptor can be determined in a competition experiment by using a structural analog that contains a reporter group. Many plotting and numerical analysis methods have been developed to calculate the binding constant of unlabeled ligand from the displacement experiments. However, a common problem with these plotting methods is that the equation transformations inevitably result in non-standard error distribution, and thus simple linear regression can not be used to extract correct values for the parameters. In the case of the numerical analysis methods, one would be faced with the possible existence of multiple solutions. In this paper, the exact mathematical expression for describing competitive binding of two different ligands to a protein molecule is presented in terms of the total concentrations of species in the system. Thus, using a commercially available non-linear regression program, all unknown parameters for describing this system can be determined by fitting the experimental data to the algebraically explicit equation without any data transformations. The distribution curves of all the species in the system can also be constructed with this equation. It is particularly useful for the cases in which the concentrations of all the species in the system are comparable to each other. PMID- 7875312 TI - Stimulation of vgf gene expression by NGF is mediated through multiple signal transduction pathways involving protein phosphorylation. AB - The vgf gene encodes one of the most rapidly induced neuronal mRNAs identified in NGF-treated PC12 cells. Maximal inhibition of VGF mRNA induction was achieved using K-252a, an inhibitor of the NGF-receptor Trk tyrosine kinase, and by mutating both Y490 (SHC association site) and Y785 (PLC-gamma 1 association site) of Trk. Inhibitors of the NGF-activated protein kinase N (PKN) were found to partially and in some cases transiently block VGF induction by NGF while in PKA deficient PC12 cells, VGF induction by NGF was comparable to that observed in parental PC12 cells. The binding of NGF to Trk therefore activates redundant signal transduction pathways which converge to regulate vgf gene expression. PMID- 7875314 TI - Transcriptional silencing of human Alu sequences and inhibition of protein binding in the box B regulatory elements by 5'-CG-3' methylation. AB - In earlier work, we demonstrated that 5'-CG-3' methylation inhibits the transcriptional activity of human Alu elements associated with the alpha 1-globin and the angiogenin genes in a cell-free transcription system from HeLa nuclear extracts. These studies have been extended to different Alu sequences and to investigations on the mechanism involved in transcriptional silencing by methylation. By comparing the results of DNase I and dimethyl sulfate (DMS) in vitro footprinting on a consensus sequence in the RNA polymerase III promoter control B region between the unmethylated and the 5'-CG-3' methylated B box, evidence has been adduced for effects of 5'-CG-3' methylation on the interaction of specific nuclear proteins with DNA sequences in the B control region of the Alu elements. These results are consistent with the interpretation that the 5'-CG 3' methylation interferes with the binding of proteins that are essential for the function of the B control region in these RNA polymerase III-transcribed elements, and that promoter methylation thus inhibits transcription. PMID- 7875315 TI - Expression, purification and subunit-binding properties of cohesins 2 and 3 of the Clostridium thermocellum cellulosome. AB - The enzymatic subunits of the cellulosome of Clostridium thermocellum are integrated into the complex by a major non-catalytic polypeptide, called scaffoldin. Its numerous functional domains include a single cellulose-binding domain (CBD) and nine subunit-binding domains, or cohesin domains. Two of the cohesin domains, together with the adjacent CBD, have been cloned and expressed in Escherichia coli, and the recombinant constructs were purified by affinity chromatography on a cellulosic matrix. Both cohesin domains, which differ by about 30% in their primary structure, showed a similar binding profile to the cellulosomal subunits. Calcium ions enhanced dramatically this binding. Under the conditions of the assay, only one major catalytic subunit of the cellulosome failed to bind to either cohesin domain. The results indicate a lack of selectivity in the binding of cohesin domains to the catalytic subunits and also suggest that additional mechanisms may be involved in cellulosome assembly. PMID- 7875316 TI - Solution structure of the DNA binding domain of a nucleoid-associated protein, H NS, from Escherichia coli. AB - The three-dimensional structure of the C-terminal domain (47 residues) obtained from the hydrolysis of H-NS protein with bovine trypsin was determined by NMR measurements and distance geometry calculations. It is composed of an antiparallel beta-sheet, an alpha-helix and a 3(10)-helix which form a hydrophobic core, stabilizing the whole structure. This domain has been found to bind to DNA. Possible DNA binding sites are discussed on the basis of the solution structure of the C-terminal domain of H-NS. PMID- 7875317 TI - Phosphorylation and accumulation of tau without any concomitant increase in tubulin levels in Chinese hamster ovary cells stably transfected with human tau441. AB - Eucaryotic expression vectors bearing a 1.4 kb cDNA encoding the 4 repeat isoform of human tau, tau441, in either the sense or anti-sense orientation with respect to a cytomegalovirus (CMV) promoter were constructed. The resulting constructs were used to transiently express tau in Chinese Hamster Ovary cells and to generate non-neuronal stable cell lines. Immunocytochemical studies of these cells show that tau is expressed in the sense but not the anti-sense or vector containing lines. Some of the cells expressing tau showed fine elongated processes which were stained by tau antibodies. The general tau immunostaining pattern appeared diffuse and punctuate. The expressed tau was seen both unbound and bound to microtubules. In some cells labeling with antibodies that specifically recognize hyperphosphorylation of tau was observed. The size of this population increased with increasing numbers of cell passages. However, no increase in steady-state tubulin level was observed following tau441 expression. These studies show that tau can accumulate in the cells without a concomitant increase in tubulin. PMID- 7875318 TI - Voltage-dependent inactivation in a cardiac-skeletal chimeric calcium channel. AB - The loci for inactivation in calcium channel proteins are unknown. Mechanisms for inactivation may be distributed across Ca2+ channel subunits and appear to be complex, multiple and interacting. We took advantage of the properties of chimeras, constructed between cardiac (H4) and skeletal muscle (Sk4) calcium channel alpha 1 subunits to study the molecular mechanism of inactivation in L type calcium channels. Sk1H3, a chimeric construct of these two L-type calcium channels, was expressed in Xenopus oocytes in the absence of auxiliary subunits. Sk1H3 incorporated repeat I from skeletal muscle alpha 1 and repeats II, III, IV from heart alpha 1 subunit. Sk1H3 inactivated faster (tau = 300 ms) and more fully than the wild-type H4 with Ba2+ ions as the charge carrier. Thus, inactivation of Sk1H3 was 90% complete after a 5-s conditioning pulse at +20 mV while inactivation of H4 was only 37% complete. Sk1H3 inactivation also developed at more negative potentials with E0.5 = -15 mV as compared to E0.5 = -5 mV for H4. In the presence of external calcium ions, the extent of inactivation significantly increased from 37 to 83% for H4 while inactivation of Sk1H3 was only slightly increased. Inactivation with Ba2+ as the charge carrier was confirmed at the single- channel level where averaged single-channel ensembles showed a similar rate of inactivation. Collectively, these observations demonstrate that Sk1H3 inactivation appears to have a prominent voltage-dependent component. Whether Sk1H3 inactivation involves interactions within repeat I alone or interactions between repeat I and site(s) located in the three other repeats of the alpha 1 subunit has yet to be determined. PMID- 7875319 TI - Nitrite and nitric oxide reduction in Paracoccus denitrificans is under the control of NNR, a regulatory protein that belongs to the FNR family of transcriptional activators. AB - The nir and nor genes, which encode nitrite and nitric oxide reductase, lie close together on the DNA of Paracoccus denitrificans. We here identify an adjacent gene, nnr, which is involved in the expression of nir and nor under anaerobic conditions. The corresponding protein of 224 amino acids is homologous with the family of FNR proteins, although it lacks the N-terminal cysteines. A mutation in the nnr gene had a negative effect on the expression of nitrite and nitric oxide reductase. Synthesis of membrane bound nitrate reductase, of nitrous oxide reductase, and of the cbb3-type cytochrome c oxidase were not affected by mutation of this gene. These results suggest that denitrification in P. denitrificans may be governed by a signal transduction network that is similar to that involved in oxygen regulation of nitrogen metabolism in other organisms. PMID- 7875320 TI - Molecular cloning of a novel C or gamma type chemokine, SCM-1. AB - From human PBMC stimulated with PHA, we have isolated cDNA clones encoding a novel cytokine named SCM-1, which is significantly related to the CC and the CXC chemokines but has only the 2nd and the 4th of the four cysteines conserved in these proteins. Its gene is also distinctly mapped to human chromosome 1. SCM-1 is strongly induced in human PBMC and Jurkat T cells by PHA stimulation. Among various human tissues, SCM-1 is expressed most strongly in spleen. SCM-1 is found to be 60.5% identical to lymphotactin, a recently described murine lymphocyte specific chemokine, which also retains only two cysteines. SCM-1 and lymphotactin may thus represent the human and murine prototypes of a novel C or gamma type chemokine family. PMID- 7875321 TI - Cross-linking of galectin 3, a galactose-binding protein of mammalian cells, by tissue-type transglutaminase. AB - The 30 kDa beta-galactoside-binding protein of baby hamster kidney (BHK) cells [Mehul et al. (1994), J. Biol. Chem. 269, 18250-18258] homologous to galectin 3, a widely distributed mammalian lectin, has been found to be a substrate for tissue type transglutaminase, as shown by the incorporation in a calcium- and time-dependent manner of 5-(biotinamido) pentylamine in the presence of guinea pig liver transglutaminase. The amino-terminal domain of hamster galectin 3, which is a repetitive sequence rich in glutamine, tyrosine, glycine and proline, is also an excellent substrate. A single lysine residue in the N-terminal domain is an essential requirement for transglutaminase-mediated oligomerization, and two equivalent glutamine residues present in identical sequence repeats within this domain appear to be involved as amine acceptors in cross-linking reactions. Transglutaminase-mediated cross-linking of galectin 3 to itself or to matrix components may be one mechanism for stabilisation of a multivalent binding form of the lectin in cell secretions or in extracellular matrices. PMID- 7875322 TI - Tamoxifen inhibits uptake and metabolism of ethanolamine and choline in multidrug resistant, but not in drug-sensitive, MCF-7 human breast carcinoma cells. AB - Tamoxifen (TAM), a widely used agent in the hormonal therapy of breast cancer, is also an antagonist of P-glycoprotein (P-gp), a cell surface protein which confers drug resistance to cells. Here we report that in an estrogen receptor-deficient multidrug-resistant subline of MCF-7 human breast carcinoma cells (MCF-7/MDR), but not in the parent drug-sensitive cells (MCF-7/WT), clinically relevant concentrations (1-5 microM) of TAM inhibited the uptake and phosphorylation of ethanolamine and choline. These inhibitory effects resulted in decreased synthesis of the corresponding phospholipids. In view of the known dependence of P-gp function on phosphatidylethanolamine (PtdEtn), inhibition of PtdEtn synthesis may represent an additional mechanism by which TAM inhibits P-gp mediated drug efflux. PMID- 7875323 TI - Characterization of the hormone binding site of natriuretic peptide receptor-C. AB - The hormone binding site of rat and human natriuretic peptide clearance receptor (NPR-C), a single transmembrane receptor, has been further refined by mutagenesis. In addition to residue 188 (rat Ala, human Ile), which completely inverts the pharmacology of the rat and human receptors [Engel et al. (1994) J. Biol. Chem. 269, 17005-17008], we report a second key residue at position 205 (rat Tyr, human Asn) which modulates affinity to a limited number of ligands. Orthologous mutation of both residues results in tighter binding for human and weaker binding for rat NPR-C. The ligand binding fold of the receptor is formed by at least the first half of the extracellular domain containing two intramolecular disulfide loops, with the two affinity-modulating residues 188 and 205 in the second loop. PMID- 7875324 TI - Involvement of intact inositol-1,4,5-trisphosphate-sensitive Ca2+ stores in cell cycle progression at the G1/S boundary in serum-stimulated human fibroblasts. AB - Thapsigargin, a selective inhibitor of the endoplasmic reticulum Ca2+ pump, has been shown to deplete inositol-1,4,5-trisphosphate-sensitive Ca2+ stores. Here we report that when thapsigargin was introduced to serum-stimulated human fibroblasts at a time point just before the G1/S boundary, it completely inhibited expression of cyclin A, activation of p33CDK2 cyclin-dependent kinase and initiation of DNA synthesis. In contrast, the Ca2+ mobilizing ionophore ionomycin was without effect. These findings indicate that Ca2+ inside the inositol-1,4,5-trisphosphate-sensitive Ca2+ stores plays a pivotal role for traverse across the G1/S transition point. PMID- 7875325 TI - A yellow component associated with human transthyretin has properties like a pterin derivative, 7,8-dihydropterin-6-carboxaldehyde. AB - Transthyretin (TTR) in plasma is associated with yellow compounds. Their properties differ, and in the chicken protein a major yellow compound has recently been identified as a carotenoid, lutein, also called xanthophyll. We now show that the major yellow component extracted from human TTR has properties like a pterin derivative, 7,8-dihydropterin-6-carboxyaldehyde (2-amino-4-hydroxy-6 formyl-7,8-dihydropteridine). The human TTR derivative has chromatographic and spectral properties identical to a yellow photochemical degradation product of biopterin and a spectrum like that of the pterin aldehyde. PMID- 7875326 TI - The analysis of modified peroxisome proliferator responsive elements of the peroxisomal bifunctional enzyme in transfected HepG2 cells reveals two regulatory motifs. AB - Peroxisome proliferators (PPs) are non-genotoxic carcinogens in rodents. They can induce the expression of numerous genes via the heterodimerization of two members of the steroid hormone receptor superfamily, called the peroxisome proliferator activated receptor (PPAR) and the 9-cis retinoic acid receptor (RXR). Many of the PP responsive genes possess a peroxisome proliferator response element (PPRE) formed by two TGACCT-related motifs. The bifunctional enzyme (HD) PPRE contains 3 such motifs, creating DR1 and DR2 sequences. PPAR and RXR regulate transcription via the DR1 element while DR2 modulates the expression of the gene via auxiliary factors in HepG2 cells. PMID- 7875327 TI - An 8.5-kDa ribonuclease from the extreme thermophilic archaebacterium Sulfolobus solfataricus. AB - Protein p3, a ribonuclease we previously isolated from the archaebacterium Sulfolobus solfataricus [P. Fusi et al. (1993) Eur. J. Biochem. 211, 305-310], was subjected to complete amino acid sequencing. It consisted of 75 residues, with a calculated M(r) of 8582, a pI of 10.1, and had some degree of monomethylation at Lys-4 and Lys-6. p2, a previously sequenced, 62-residue ribonuclease from the same organism, had an identical sequence for 57 consecutive residues starting from the N-terminus. p2 and p3 also showed a striking similarity to five other proteins previously isolated from Sulfolobus strains and identified as DNA-binding proteins. However, the C-terminus, 10 residue region of p3 did not show any similarity to these proteins; in contrast, it was significantly similar to stretches in three eubacterial ribonucleases from Bacillus strains. No difference between p2 and p3 has so far been detected as regards their catalytic properties. Available data suggest that these molecules have a narrow substrate specificity and probably play specific roles in RNA processing. PMID- 7875328 TI - mRNA encoding the translation initiation factor eIF-4E is expressed early in Xenopus embryogenesis. AB - The translation initiation factor eIF-4E plays an important role in regulating the overall rate of translation in eukaryotic cells. To investigate the expression of eIF-4E itself, we characterized the eIF-4E mRNA expressed in Xenopus embryos. 5'-RACE was performed to determine the 5'-end of the mRNA and the result predicts isoforms differing at the amino-terminal end. Expression of the eIF-4E mRNA in Xenopus oocytes and embryos was examined by RT-PCR. Xenopus eIF-4E mRNA is produced during oogenesis and persists during the early stages of embryogenesis as a maternal mRNA. PMID- 7875329 TI - The expression of esterase S gene of Drosophila virilis in Drosophila melanogaster. AB - Drosophila melanogaster was transformed with the esterase S gene from Drosophila virilis. This gene is strongly activated in ejaculatory bulbs of mature males of Drosophila virilis. The closely related gene from Drosophila melanogaster is activated in ejaculatory ducts. The tissue- and stage-specific expression of incomplete genomic copy of the esterase S gene integrated into the Drosophila melanogaster genome is the same as in Drosophila virilis. These data show that tissue and stage specificity is determined by relatively small 5' regulatory region of the esterase S gene. The comparison between deduced amino-acid sequences of the esterase S of Drosophila virilis and esterase 6 of Drosophila melanogaster was performed. These sequences revealed 50% homology. PMID- 7875330 TI - Unique molecular properties of superoxide dismutase from teleost fish skin. AB - A unique Cu,Zn-SOD was found and isolated from plaice Paralichthys olivaceus skin. Surprisingly, the properties of purified fish skin SOD were very different from those of SOD from other sources reported so far. The purified SOD was composed of four same subunits of 16 kDa and the molecular weight of the native SOD was found to be around 65 kDa. The dominant amino acids of the SOD were Ser, Thr, Pro and Glu. Above 70 degrees C, thermostability of the SOD was much lower than that of bovine erythrocyte Cu,Zn-SOD. PMID- 7875331 TI - Influence of the hydrophobicity of lipase isoenzymes from Candida rugosa on its hydrolytic activity in reverse micelles. AB - Two isoenzymes of Candida rugosa lipase, having the same mol.wt., size and similar aminoacid sequence, were studied in reverse micelles of AOT. The results demonstrated the relevance of lipase hydrophobicity in reactions in anionic micelles. This is a key factor in mitigating the inhibition effect of charged micelles. The more hydrophobic isolipase A was a better biocatalyst for hydrolytic processes in these systems. Its alpha-helix content increased from 31% to 49% of the total structure in reverse micelles. A fluorescence study indicated a more apolar environment for the more hydrophobic isolipase A. Emission spectra of this isolipase in the AOT systems were blue shifted. At omega 0 values where each isolipase presented its maximum activity, a decrease of the emission intensity of Trp was found. An enzyme and substrate dependence of optimal omega 0 is reported. The different interaction of isolipases A and B with the micellar system produced an opposite omega 0 dependence to their stabilities. The more hydrophobic lipase A had higher stability at higher droplet sizes. PMID- 7875332 TI - Identification of reactive lysines in phosphoenolpyruvate carboxykinases from Escherichia coli and Saccharomyces cerevisiae. AB - Escherichia coli and Saccharomyces cerevisiae phosphoenolpyruvate carboxykinases (PEPCKs), were inactivated by pyridoxal 5'-phosphate followed by reduction with sodium borohydride. Concomitantly with the inactivation, one pyridoxyl group was incorporated in each enzyme monomer. The modification and loss of activity was prevented in the presence of ADP plus Mn2+. After digestion of the modified protein with trypsin plus protease V-8, the labeled peptides were isolated by reverse-phase high-performance liquid chromatography and sequenced by gas-phase automatic Edman degradation. Lys286 of bacterial PEPCK and Lys289 of the yeast enzyme were identified as the reactive amino acid residues. The modified lysine residues are conserved in all ATP-dependent phosphoenolpyruvate carboxykinases described so far. PMID- 7875333 TI - Fraction A of armadillo submandibular glycoprotein and its desialylated product as sialyl-Tn and Tn receptors for lectins. AB - Fraction A of the armadillo submandibular glycoprotein (ASG-A) is one of the simplest glycoproteins among mammalian salivary mucins. The carbohydrate side chains of this mucous glycoprotein have one-third of the NeuAc alpha 2-->6GalNAc (sialyl-Tn) sequence and two thirds of Tn (GalNAc alpha-->Ser/Thr) residues. Those of the desialylated product (ASG-Tn) are almost exclusively unsubstituted GalNAc residues (Tn determinant). When the binding properties of these glycoproteins were tested by a precipitin assay with Gal, GalNAc and GlcNAc specific lectins, it was found that ASG-Tn reacted strongly with all of the Tn active lectins and completely precipitated Vicia villosa (VVL both B4 and mixture of A and B), Maclura pomifera (MPA), and Artocarpus integrifolia (jacalin) lectins. However, it precipitated poorly or negligibly with Ricinus communis (RCA1); Dolichos biflorus (DBA); Viscum album, ML-I; Arachis hypogaea (PNA), and Triticum vulgaris (WGA). The reactivity of ASG-A (sialyl-Tn) was as active as that of ASG-Tn with MPA and less or slightly less active than that of ASG-Tn with VVL-A+B, VVL-B4, HPA, WFA, and jacalin, as one-third of its Tn was sialylated. These findings indicate that ASG-A and its desialylated product (ASG-Tn) are highly useful reagents for the differentiation of Tn, T (Gal beta 1-->3GalNAc), A (GalNAc alpha 1-->3Gal) or Gal specific lectins and monoclonal antibodies against such epitopes. PMID- 7875334 TI - [Dental status and treatment requirements of the elderly population of Gyor, a major Hungarian city (I)]. AB - We performed a 'random sampling' oral health survey in a Hungarian city among the elderly population. This examination was a part of an International Standard Research. The most important result of this survey is, the high number of toothless and edentulous persons. Therefore, the demand for periodontal and restorative treatment is unimportant from the point of view of epidemiology. We emphasize, that it is very important to save the remains of dentition by improvement of personal ral hygiene, regular scaling and crown or bridgework in addition to prosthetic rehabilitation. PMID- 7875335 TI - [Stress capacity and extension of total removable prostheses]. PMID- 7875336 TI - [Centenary of Prof. Karoly Balogh, D.D.S]. PMID- 7875337 TI - [Brief history of the Federation Dentaire Internationale (FDI)]. AB - FDI was founded in 1900, Paris, 95 years ago. At this International Dental Congress professors Jozsef Arkovy and Lajos Ottofy both held lectures. The Hungarian Dental Association (HDA) could join FDI, however, only in 1966. Today close contacts and collaboration are developing between HDA and FDI. PMID- 7875338 TI - [Experience with partial removable dentures anchored by the Vigano attachment]. AB - In 1993 the Vigano attachment appeared in Hungarian commercial turnover. On the basis of 20 cases observed during one year it can be stated, that the use is simple for dental technicians, the fitting effect is good, requires small place, insertion and removal is easy for elderly and handicapped patients; it is aesthetically satisfying and the design ensures minimum likelihood of repairs. PMID- 7875339 TI - [Burstone's segmented arch technic]. AB - The authors have introduced the segmented arch technique of Burstone on the base of the literature and of own experiences. They are reporting about the theory and the advantages of the technique and its adaptability in the daily orthodontic practice. PMID- 7875340 TI - [Effect of preparation methods on the adaptability of conventional amalgams and amalgams without gamma-2-phase]. AB - Experimental investigations with "Goodfill 700" and "Starfill NG2" amalgams showed, that the adaptability and plasticity depend not only on characteristics of the powder, but are influenced by mixing ratios resp. methods of condensation. Fillings performed from "Starfill NG2", possessing a higher content of powder, but in spherical and smaller particles, have a better adaptability, however a more loose structure at the edges. In case of manual condensation the authors recommend, that the "Dentomat 2" equipment should be used with NG2 at the "0.5", and with G700 at the "-0.5" calibration point. PMID- 7875341 TI - [Possibilities for improvement of the surface properties of dental implants (2). The use of ceramic oxides in surface coating for titanium and tantalum implants]. AB - A corrosion-resistant, 2000-2500 A thick, ceramic oxide layer with a coherent crystalline structure was produced on the surface of titanium implants. The layer contains a bioactive component, it is made from the material of the implant, adheres well and gives an aesthetically pleasant impression. The coated implants were subjected to various physical, chemical electronmicroscopic, etc. tests for their qualitative characterization. These tests demonstrated the good properties of the implants. The procedure is protected internationally by patents. PMID- 7875343 TI - Educational program for physicians. PMID- 7875344 TI - The year of managed care--public programs. PMID- 7875345 TI - Dental amalgam: villain or vassal? PMID- 7875342 TI - [Bibliography of the professional writings of Prof. Karoly Balogh]. AB - Professor K. Balogh published between 1924-1972 175 scientific papers, 32 in German-, 21 in English language. He was author resp. co-author of 9 books in Hungarian and German language. PMID- 7875347 TI - Consent. AB - Before a dental practitioner examines a patient he or she must obtain the patient's consent to do so, and before undertaking any form of complex or expensive treatment the patient's consent must be in writing. Failure to do this could leave the practitioner open to prosecution for assault, and liable for damages in a civil court. PMID- 7875346 TI - The provision of emergency dental care by general dental practitioners in an urban area. AB - The provision of emergency care by dental practitioners in the Manchester area was assessed by a postal questionnaire. A 54.8% response rate was obtained. The average number of emergency patients treated by respondents per working day was 3.2; the practitioners seeing these patients principally by 'double booking' appointments. One-third of the respondents claimed to provide specific slots for treating dental emergencies, which could be related to the amount of NHS work undertaken. Out-of-hours emergencies were delegated to a third party by 46.3% of practitioners who replied to the questionnaire. PMID- 7875348 TI - Sugar-containing or sugar-free paediatric medicines: does it really matter? AB - The long-term use of sugar-containing medicines has long been considered a cause of dental caries in children. Several studies have examined the role of prescription medicines in dental decay, but what about those that can be bought over the counter and that are used infrequently? In this paper practitioners are advised on how to encourage parents to use sugar-free medicines for the sake of their children's teeth. PMID- 7875349 TI - An update on conventional fixed bridges: 2. Designing fixed bridgework. AB - Most patients who have lost teeth prefer a fixed prosthesis to a removable prosthesis. In this, the second article in the series, we consider the principles of design that are applicable to conventional fixed bridgework and which will enable the clinician to select the prosthesis most appropriate for a partially dentate patient. PMID- 7875350 TI - A review of temporary crowns and bridges. AB - Successful crown and bridgework relies heavily upon the precise use of temporary restorations. It is the importance of this stage in crown and bridgework, perhaps more than any other, that is so often underestimated. This article reviews the materials currently available for temporary restorations and assesses the various methods of construction. PMID- 7875351 TI - Oral and dental problems in the organ transplant patient. AB - The number of people receiving organ transplants has dramatically increased over the last decade. It is now likely that a dental surgeon will come across patients who have undergone transplantation. This paper considers the particular problems that these patients are likely to present their general dental practitioners. PMID- 7875352 TI - Ethical dilemmas in dentistry. PMID- 7875353 TI - Maximizing the clinical exposure of dental students to conservative dentistry: design and evaluation of a novel system. AB - A system has been designed to maximize the clinical experience that dental students receive in the discipline of conservative dentistry. Data on each operative procedure to be carried out for each patient under a student's care is entered into a customized computer database and each student is given a printout of this information every 4 months. Students feel that this system prospectively identifies areas of treatment in which they may lack experience and provides opportunities to review and amend any inaccurate information. This paper explains how the system was set up and administered. PMID- 7875354 TI - Oral rehabilitation and quality of life following the treatment of oral cancer. AB - This is the first of two articles concerning the surgical and prosthodontic rehabilitation of patients who have undergone surgery for cancer of the mouth. This article discusses the morbidity associated with treatment and its effect on quality of life. The second article will consider aspects of the prosthodontic rehabilitation particularly with regard to obturator construction following maxillectomy. PMID- 7875355 TI - Treatment of unsightly oral pigmentation: a case report. AB - Discoloration of the oral mucosa may cause embarrassment to sufferers. In this case report, the author describes a simple, versatile and relatively non-invasive technique for treating unsightly racial pigmentation of the oral mucosa. PMID- 7875356 TI - An update on conventional fixed bridges:. 3. Planning ahead. AB - The first two articles in this series dealt with patient assessment and selection for bridgework and the available options in conventional bridgework design. Having decided to provide a conventional bridge for a patient, the practitioner must plan ahead so that the clinical execution of the bridge proceeds smoothly and successfully. Time taken to plan ahead carefully will always benefit both patient and operator. PMID- 7875357 TI - The impacted lower wisdom tooth: to remove or to leave alone? AB - The management of impacted third molars, particularly the indications for their removal, is judged against a constantly changing climate of professional opinion, public attitudes to treatment and the funding of healthcare. These changes highlight the practitioner's dilemma: to remove an impacted wisdom tooth or to leave well alone? This article discusses the indications for and risks of wisdom tooth removal, and suggests guidelines for dealing with the dilemma. PMID- 7875358 TI - Necrotizing sialometaplasia: a case report. AB - Necrotizing sialometaplasia, a benign self-limiting disease of minor salivary glands, may be confused both clinically and histologically with squamous cell carcinoma or a minor salivary gland neoplasm. Its sinister appearance has lead to misdiagnosis and some patients have undergone extensive surgery unnecessarily. This paper describes the salient features of necrotizing sialometaplasia and discusses the management of a patient with the condition. PMID- 7875360 TI - An abrogation of responsibility in the NHS. PMID- 7875359 TI - Recent advances in the management of patients with haemophilia and other bleeding disorders. AB - Much attention has been focused recently on barriers to dental care, particularly for patients with disabilities, from the perspective of the patient and the dental team. Treatment of patients with haemorrhagic disorders may cause a certain amount of anxiety in dental staff. The authors of this paper aim to reduce this anxiety by clarifying confusion between the haemorrhagic disorders and making recommendations concerning the dental care of such patients. PMID- 7875361 TI - Report on the government green paper: improving NHS dentistry. PMID- 7875362 TI - Antibiotics in general practice. AB - The human race has had to endure infections for as long as it has been on earth, and has developed efficient natural defence mechanisms to combat them. Modern medicine aims to augment these natural mechanisms, to help speed up resolution of infection and decrease morbidity and mortality. PMID- 7875363 TI - Prosthodontic rehabilitation in the maxilla following treatment of oral cancer. AB - This is the second in a two-part series on oral cancer. Part 1 focused on the surgical aspects of treatment and morbidity associated with oral cancer. In this article aspects of prosthodontic management of patients with maxillary tumours are considered, with emphasis on promoting optimal rehabilitation. PMID- 7875364 TI - The first 100 cases of orthodontic treatment: one year out of retention. AB - The Index of Orthodontic Treatment Need (IOTN) and Peer Assessment Rating (PAR) Index have been developed to assess need and outcome of orthodontic treatment. In this paper the authors evaluate the occlusal change and orthodontic treatment need of 100 consecutively started courses of orthodontic treatment at least 1 year after all retention measures had ceased using these indices. PMID- 7875365 TI - Self-medication for the control of dental pain: what are our patients taking? AB - As all dental practitioners are aware, patients suffering from dental pain often self-medicate with over-the-counter (OTC) analgesics in order to alleviate their symptoms: indeed, some patients seem to view the use of these drugs as a means of avoiding the need for dental attendance altogether. The use (and abuse) of such medication is entirely under the control of the patient. The study reported in this article shows which commonly available analgesics are chosen by patients and how effective they are considered to be. The authors also assess the overall pattern of analgesic self-medication, and discuss the problem of over consumption. PMID- 7875366 TI - A bizarre facial sinus. AB - A 63-year-old Caucasian man presented to his general dental practitioner with a spontaneously exfoliated lower central incisor and hair growing from the socket. Examination revealed a hair-filled sinus from the skin of the median aspect of his chin to the socket of the exfoliated tooth. This was confirmed histopathologically following excision biopsy. PMID- 7875367 TI - Larval spicules, cilia, and symmetry as remnants of indirect development in the direct developing sea urchin Heliocidaris erythrogramma. AB - Nonfeeding larvae of the echinoid Heliocidaris erythrogramma were raised in culture and examined for expression of a larval skeleton and for the arrangement of the ciliated band. Opaque larvae were fixed, cleared, and examined under polarized light for evidence of calcification. By 35 hr after fertilization (at 22 degrees C), a pair of triradiate spicules was present at the posterior end of the larvae. Each member of this pair formed a fenestrated spicule as it grew laterally. This pair and another pair which formed subsequently, were arranged across a plane of bilateral symmetry orthagonal to the juvenile oral aboral axis. These paired larval spicules can be identified as reduced expressions of postoral and posterodorsal rods found in plutei, and their expression indicates that the juvenile rudiment of H. erythrogramma forms on the left side and that larval body axes are conserved in this modified larva. By 44 hr the ciliated band formed as an incomplete transverse loop of three segments at the posterior end and on the dorsal surface of the ovoid larva. Cilia in these segments grew to lengths of 45 50 microns, longer than other swimming and feeding cilia reported for echinoderm larvae. Band segments are interpreted as expressions of epaulettes (specialized swimming bands) rather than the feeding ciliated band of the pluteus. The ciliated band segments and the larval spicules are both bilaterally symmetrical with respect to the same plane and indicate conserved larval bilateral symmetry despite the major asymmetry of the fates of cells on either side of this plane in their contribution to juvenile development. PMID- 7875368 TI - Temporal and spatial expression of an adult cuticle protein gene from Drosophila suggests that its protein product may impart some specialized cuticle function. AB - An adult cuticle protein gene (Dacp-1) from Drosophila melanogaster has been isolated and characterized. This gene was classified as an adult cuticle protein gene because it maintains the conserved structure of other cuticle protein genes, the sequence of its conceptual translation product contains a repeated motif that is found almost exclusively in a subset of adult cuticle proteins from Locust migratoria, and the gene is expressed in the epidermis underlying the head and thoracic cuticle. The bulk of Dacp-1 expression starts approximately 72 hr after pupariation, peaks approximately 12 hr after eclosion, and decreases thereafter to undetectable levels by 3 days after eclosion. The stage specificity and spatial restriction of Dacp-1 expression as well as the physical properties of its conceptual translation product suggest that it may be involved in some specialized function such as thickening of the adult cuticle. PMID- 7875369 TI - Cellular events during development of the olfactory sense organs in Drosophila melanogaster. AB - The olfactory sensilla on the antenna of adult Drosophila melanogaster develop during the first 36 hr after pupariation, from their anlagen in the cephalic disc. We have used tissue-specific beta-galactosidase expression in the enhancer trap strain A101.IF3 and the monoclonal antibody 22C10 as sensory cell markers, as well as the lineage tracer 5-bromo-2'-deoxyuridine (BrdU), to describe this process. The development of an olfactory sensillum begins with the selection of a "founder cell" (FC). These cells are distinct in that they possess large apically located nuclei revealed by beta-galactosidase expression in A101.IF3. In the following 6 hr, a few cells neighboring the FC also start expressing beta galactosidase and together comprise a group. Cells of this group, denoted a "presensillum-cluster" (PSC), undergo at least one round of replication and give rise to all of the cells of a sensillum. A subset of the cells within each PSC and, later, all the sensory neurons are recognized by MAb22C10. The antennae of the mutant lozenge3 (lz3) lack all basiconic and some trichoid sensilla. The mutation apparently affects early steps in sensillum development and many of the FCs fail to form. Those that are present, however, proceed to form mature olfactory sensilla. Therefore, we conclude that the selection of an FC is the first step in olfactory sense organ development. Our study reveals novel aspects of sensory development in Drosophila. PMID- 7875370 TI - Identification and partial characterization of yolk and cortical granule proteins in eggs and embryos of the starfish, Pisaster ochraceus. AB - The unfertilized oocyte contains various granules which serve as storage sites for proteins, the majority which are yolk granules or platelets. Yolk granules are thought to provide the developing embryo with nutrients essential for its survival, while other granules contain proteins such as enzymes and extracellular matrix components that are required for fertilization and perhaps for early development. This study uses immunofluorescence and immunogold techniques with two novel monoclonal antibodies against proteins found in egg yolk and cortical granules to study the localizations of these antigens during early starfish development. Partial biochemical characterizations using the anti-yolk antibody have revealed that there are a family of structurally related proteins in oocyte yolk granules and that while the molecular compositions of the yolk proteins change during embryogenesis, their depletion is not significant until the larval stage, suggesting these proteins are not required for early development. In addition, a large immunoreactive protein has been found in the intestine and coelomic fluid, suggesting that, as in other species, the starfish yolk proteins may be derived from a large precursor, such as vitellogenin. Analysis of the anti cortical granule antibody has revealed that a 120-kDa antigen is stored in antibody has revealed that a 120-kDa antigen is stored in cortical granules of unfertilized eggs. Upon egg activation, the cortical granules located in the peripheral egg cytoplasm undergo exocytosis, and the 120-kDa antigen is released into the perivitelline space. However, other granules, which are also labeled by this antibody, remain dispersed throughout the egg cytoplasm and are still present in the early gastrula, where they appear to contribute to the extracellular matrices of the developing embryo. This suggests that starfish cortical granules play a dual function: At fertilization, where they help create a block to polyspermy, and in embryonic development, where they secrete extracellular matrix components. PMID- 7875371 TI - Former neuritic pathways containing endogenous neural agrin have high synaptogenic activity. AB - When Xenopus spinal cord (SC) neurons are grown on an appropriate substrate of basal lamina molecules, the agrin they externalize along their neuritic outgrowth remains bound to the substrate even after the neurons are removed. Here we demonstrate that these former neuritic pathways containing substrate-bound, neural agrin cause an accumulation of acetylcholine receptors (AChR) and cholinesterase (ChE) at sites of contact with muscle cells and inhibit AChR aggregation over the rest of the muscle cell surface. These local and global synaptogenic effects were not triggered by former neuritic pathways that were agrin-negative. The length of AChR accumulation along the agrin pathways contacted by individual muscle cells corresponded to a saturation process, in agreement with the notion that muscle cells have a limited capacity to cluster AChR. The AChR accumulation caused by the agrin pathways was almost twice as extensive as that induced by living neurites. It is concluded that agrin and possibly other synaptogenic molecules externalized by competent SC neurons bind to the culture substrate in quantities which are more than sufficient to account fully for the local and global changes in AChR and ChE distribution associated with embryonic nerve-muscle synaptogenesis. PMID- 7875372 TI - QCE-6: a clonal cell line with cardiac myogenic and endothelial cell potentials. AB - A clonal cell line (QCE-6) sharing many properties with splanchnic mesodermal cells has been derived from 20-methylcholanthrene-treated cardiogenic mesoderm of the Japanese quail. QCE-6 cells which have been stably maintained for over 4 years in vitro display positive staining with antibodies to cytokeratin, vimentin, cingulin, and N-cadherin but were negative for markers of endothelial, fibroblastic, smooth, and skeletal muscle cell lineages. In the present study, we show that addition of retinoic acid and growth factors initiated cardiomyogenic differentiation in approximately 50% of QCE-6 cells as indicated by the expression of muscle- and cardiac-specific proteins. The distribution of these proteins in induced cells was similar to precontractile cardiac myocytes. In addition to these myogenic cells, cultures of induced QCE-6 cells contained endothelial cells as visualized by the presence of QH1 antigen and extracellular matrix molecules associated with endothelial cells. These data demonstrate that the QCE-6 cell is a progenitor of both cardiac myogenic and endothelial cell lineages and along with other recent studies (Linask and Lash, 1993; Garcia Martinez and Schoenwolf, 1993) suggest that these two cell lineages may have a common embryonic origin. PMID- 7875373 TI - Protein kinase M, the cytosolic counterpart of protein kinase C, remodels the internal cytoskeleton of the mammalian egg during activation. AB - We have investigated mechanisms by which intracellular signals act to restructure the spatial organization of the cytoskeleton as the mammalian egg is converted into the zygote. Four distinct approaches (one cytological, two biochemical, and one pharmacological) demonstrate protein kinase C (PKC) and its cytosolic active counterpart, PKM, act in succession at the time of egg activation. PKM serves to remodel the internal cytoskeleton. The cytological approach mapped the distribution of kinase over time using the PKC reporter dye, Rim-1, which demonstrated a temporal shift in kinase distribution from its initial site of activation at the plasma membrane to its subsequent association with a cross linked network of intermediate filaments referred to as sheets. The first of two biochemical analyses, Western blot analysis, demonstrated that eggs activated with calcium ionophore contained PKC in the detergent-soluble fraction and PKM in the sheet enriched fraction. Prior to egg activation, PKM is not detected in the sheet-enriched fraction; only PKC is detected in the detergent-soluble fraction of these eggs. The second biochemical analysis demonstrated, via [32P]ATP labeling of a known PKC substrate, that the PKM generated from activation of PKC in response to activation of eggs with calcium ionophore is an active kinase and is located in the sheet-enriched fraction. In addition, purified forms of PKM, but not PKC, could be shown to act on the internal cytoskeleton when perfused into a permeabilized egg system. Pharmacological treatments demonstrate that elevation of [Ca2+]i does not act directly to alter the internal cytoskeleton of the egg. Our results suggest that this kinase is employed at the time of fertilization to provide an internal chronometer acting first at the cell periphery as PKC and subsequently in the cell interior as PKM. PMID- 7875374 TI - The influence of glucose, cumulus cells, and metabolic coupling on ATP levels and meiotic control in the isolated mouse oocyte. AB - The effects of glucose and cumulus cells on oocyte ATP levels and germinal vesicle breakdown (GVB) in isolated mouse oocytes have been examined. Oocyte cumulus cell complexes or denuded oocytes (DO) from pregnant mare serum gonadotropin-primed immature mice were cultured in minimum essential medium containing 4 mM hypoxanthine and 1 mM pyruvate, in the absence or presence of 0.55 mM glucose. After 17-18 hr in the presence of glucose, ATP in both the oocyte-cumulus cell complexes and oocytes derived from such complexes (cumulus cell-enclosed oocytes; CEO) was elevated, and less than one-half of the oocytes had resumed maturation (48% GVB). Removal of glucose caused a decrease in ATP levels in complexes and CEO and reversed the meiotic arrest in CEO (98% GVB), and these effects were mimicked by iodoacetate treatment. Higher frequencies of GVB were observed in glucose-free medium after more than 6 hr of culture, while ATP levels were reduced within 3 hr. Glucose had no effect on ATP levels or the meiotic state of denuded oocytes. Interestingly, iodoacetate had a stimulatory effect on GVB in DO (86% GVB compared to 57% in controls), but did not effect ATP levels. Glycerrhetinic acid, a gap junction uncoupler, completely suppressed oocyte-cumulus cell coupling in cultured complexes (0.15% coupling compared to 16.6% in controls) and reversed the inhibitory effect of glucose on oocyte maturation (91 and 95% GVB at 10 and 25 microM compared to 42% GVB in controls). This agent also prevented follicle-stimulating hormone-induced meiotic maturation in dibutyryl cAMP-arrested CEO. These results thus implicate mediation by gap junctions of both inhibitory and stimulatory signals from the cumulus cells. Comparison of ATP levels in spontaneously maturing CEO in vitro with those from oocytes maturing in vivo in response to human chorionic gonadotropin revealed that a decrease in oocyte ATP preceded or accompanied GVB in spontaneously maturing oocytes but not in those maturing in vivo. The results of this study indicate that glucose-derived elevation of oocyte ATP contributes to meiotic arrest in cumulus cell-enclosed oocytes that is dependent on patient gap junctions. Furthermore, a model for reinitiation of oocyte maturation is supported in which spontaneous GVB results from cessation or interruption of inhibitory influences, while ligand-provoked GVB is brought about by the generation of stimulatory signals that override inhibitory input. PMID- 7875375 TI - Isolation and characterization of ovochymase, a chymotrypsin-like protease released during Xenopus laevis egg activation. AB - A chymotrypsin-like protease contained in the perivitelline space of unactivated Xenopus eggs is released during egg activation and appears to participate in vitelline envelope conversion. This 30-kDa protease, which we have termed ovochymase, was isolated from the exudate of activated eggs using a soy bean trypsin inhibitor-agarose affinity column. The column eluant contained only two proteins, the 30-kDa ovochymase plus a 78-kDa chymotrypsin-like proteolytic activity. The 78-kDa protease was not usually observed in fresh egg exudate samples and thus was activated during the purification process and may represent the proposed precursor of the 30-kDa protease. The 30- and 78-kDa proteases were separated by gel filtration HPLC or by SDS-PAGE. The N-terminal amino acid sequence of SDS-PAGE-isolated ovochymase was determined to be VVGGQQAAPR. This conserved amino acid sequence, plus active site specific inhibition and substrate specificity studies, places ovochymase in the serine protease I family of enzymes. A two-dimensional protease activity gel revealed that ovochymase is present as several isozymes with a wide range of pI's. PMID- 7875376 TI - An orthodenticle-related protein from Strongylocentrotus purpuratus. AB - Orthodenticle-related proteins function as regulators of head formation and other developmental events in flies and mice. Here, we characterize a cDNA clone encoding an orthodenticle-related protein from the sea urchin Strongylocentrotus purpuratus. The cDNA, termed SpOtx, has a highly conserved orthodenticle homeobox but otherwise diverges in sequence from its fly and mouse counterparts. Orthodenticle-related proteins bind with high affinity to DNA containing the sequence motif TAATCC/T. The S. purpuratus aboral ectoderm-specific Spec2a gene has several TAATCC/T sites in its control region, and we provide evidence, using bandshift analysis, that Spec2a may be target gene for SpOtx. Two SpOtx transcripts accumulate during embryogenesis, an early transcript whose level peaks at blastula stage and a late transcript accumulating to highest concentrations at gastrula stage. SpOtx transcripts were found initially in all cells of the cleaving embryo, but they gradually became restricted to oral ectoderm and endoderm cells. In contrast, SpOtx protein was found in nuclei of all cells at both blastula and pluteus stages. Our results suggest that SpOtx plays a role in the activation of the Spec2a gene and most likely has additional functions in the developing sea urchin embryo. PMID- 7875377 TI - undulated phenotypes suggest a role of Pax-1 for the development of vertebral and extravertebral structures. AB - undulated extensive mice carry a deletion of at least 28.2 kb, removing the terminal Pax-1 exon including the poly(A) signal. This mutation leads to a drastically reduced amount of Pax-1 transcript. The similarity in phenotype between unex and the point mutation un suggests both to be functionally equivalent. A third mutant, Undulated short tail, harbors a deletion of at least 48.3 kb, eliminating the Pax-1 locus as well as 38 kb of flanking sequences. Phenotypically, this mutant differs from un and unex. The comparative phenotype analysis of all undulated alleles revealed morphological alterations in the vertebral column, the sternum, the scapula, the facial skeleton, and the thymus that correspond to Pax-1 expression domains. The vertebral column phenotype is characterized by the reduction of vertebral components. These reductions can be traced back to the delayed cell accumulation in the embryonic sclerotome while the principal organization of this tissue is maintained. The morphological alterations outside the vertebral column are likewise confined to size reductions. Therefore, Pax-1 may exert similar functions in all of its expression domains. PMID- 7875378 TI - The effects of target tissues on the outgrowth of chick cutaneous and muscle sensory neurons. AB - In some developing systems, growing axons are attracted to their target site by a diffusible molecule released by the target tissue. In the chick hindlimb, this mechanism could explain how axons, after having reached the plexus region, grow to muscle or to skin. To begin to test this possibility for limb-innervating sensory neurons, we cocultured dorsal root ganglion explants and potential target tissues in three-dimensional collagen gels. In particular, we wanted to know if target tissues, at early stages of development, specifically attract axons of only the appropriate type of sensory neuron. To identify each type of sensory neuron, we used DiI to retrogradely label either cutaneous or muscle sensory neurons in the embryo, prior to culturing. The results showed that dermal and muscle explants could each enhance the outgrowth of both cutaneous and muscle sensory axons. In contrast, the epidermis and the connective tissue associated with developing muscle appeared to inhibit the outgrowth of both cutaneous and muscle sensory axons. These results suggest that, in the embryo, the dermis and muscle cells both release diffusible factors that cause sensory axons to diverge from the plexus, extend toward the sources of these factors, and thereby form discrete peripheral nerves. The inhibitory effects of epidermis and muscle associated connective tissue may serve to limit the growth of sensory axons to the structures, i.e., dermis and muscle cells, that ultimately receive sensory innervation. However, since for each of the difference types of limb tissue, the responses of cutaneous and muscle sensory neurons were always similar to one another, sensory axons must not be responding to target-derived factors when they decide whether to grow to skin or to muscle. PMID- 7875379 TI - The expression of cell adhesion molecules on the growth cones of chick cutaneous and muscle sensory neurons. AB - In the developing chick hindlimb, axons that will project along a given peripheral nerve sort out together, as they traverse the plexus region at the base of the limb, and become segregated from axons that will project along other peripheral nerves. This sorting out may involve, at least in part, the differential expression of various cell adhesion molecules (CAMs). To begin to explore this possibility, we have compared the relative levels of immunofluorescent labeling on the growth cones of two populations of sensory neurons whose axons become segregated from one another: cutaneous and muscle sensory neurons. We took a tissue culture approach, since this allowed us to readily visualize the immunofluorescent labeling of individual growth cones, and identified the two cell types by previous retrograde labeling with DiI. Two dorsal root ganglion explants, one containing DiI-labeled cutaneous neurons and the other containing DiI-labeled muscle sensory neurons, from opposite sides of the same embryo, were plated together in each culture dish. For all the CAMs were studied (NCAM, polysialylated NCAM, G4/L1, axonin-1, SC1/DM-GRASP/BEN, and N cadherin), the intensity of immunofluorescent labeling typically was fairly uniform on the growth cone, it filopodia, and the portion of the neurite just proximal to the growth cone. Only one CAM, axonin-1, exhibited labeling that was especially intense at sites of interneuronal contact. Quantification of labeling intensities using image analysis showed that cutaneous and muscle sensory growth cones did not consistently differ from one another in their levels of expression of G4/L1 or of axonin-1. The latter finding stands in contrast to recent reports claiming that axonin-1 is not expressed on muscle sensory neurons. Each of the other CAMs (NCAM, polysialylated NCAM, SC1/DM-GRASP/BEN, and N-cadherin) also showed considerable overlap in the distribution of labeling intensities between the two populations, but overall, expression levels on muscle sensory growth cones were greater than on cutaneous growth cones. How the differential expression of some CAMs could potentially contribute to the way that cutaneous and muscle sensory growth cones become segregated from one another and the implications of these results for sensory neuron specification are discussed. PMID- 7875380 TI - Rat sperm plasma membrane mannosidase: localization and evidence for proteolytic processing during epididymal maturation. AB - Previous studies from this laboratory have identified a novel alpha-D-mannosidase on the sperm plasma membranes of several species, including man, which may have a role in fertilization. The polyclonal antibody raised against an isoform of the enzyme purified from rat epididymal fluid was found to cross-react with the alpha D-mannosidase activity present in the detergent-solubilized spermatozoa and sperm plasma membranes. In the present study, we have used affinity-purified as well as monospecific anti-mannosidase IgG to demonstrate that the sperm mannosidase is an integral plasma membrane component of the rat sperm and is localized on the periacrosomal region of the sperm head. In addition, we demonstrate proteolytic processing of the membrane-bound alpha-D-mannosidase during maturation of spermatozoa. The membrane fractions prepared from testis, and spermatozoa from the caput, corpus, and cauda regions of the epididymis, were solubilized in SDS and resolved by SDS-PAGE. The resolved polypeptides, when subjected to Western blot analysis using affinity-purified anti-mannosidase IgG as the primary antibody, revealed the presence of three specific immunoreactive bands (apparent M(r), 135, 125, and 115 kDa) in the membranes from testis, caput, and corpus spermatozoa. However, the cauda sperm plasma membranes showed only one immunoreactive band of apparent M(r) 115 kDa. The disappearance of the 135-and 125-kDa forms and the appearance of a sharp 115-kDa band on cauda spermatozoa suggests a precursor-product relationship between various molecular forms of the enzyme. Trypsin treatment of testicular and caput sperm membranes largely converted the precursor forms to the mature (115-kDa) form. The in vitro proteolysis resulted in an elevated level of the alpha-D-mannosidase activity in the caput (but not cauda) sperm plasma membrane. Inclusion of trypsin inhibitors (benzamidine and aprotinin) largely prevented the conversion of precursor form to the mature form. These data are consistent with the observed increase in the levels of sperm enzyme activity as spermatozoa move from the caput to the cauda region and suggest that the increase is due to the conversion of enzymatically inactive/less active high molecular weight precursor forms (135 and 125 kDa) into enzymatically active mature form (115 kDa) during sperm maturation. PMID- 7875381 TI - Oligodendroblasts distinguished from O-2A glial progenitors by surface phenotype (O4+GalC-) and response to cytokines using signal transducer LIFR beta. AB - The developmental potential of progenitors at two final stages of the macroglial lineage giving rise to oligodendrocytes in postnatal rat brain was studied in response to defined and serum inducers of astrocyte gene expression. Cell immunoselection [with Gd3 ganglioside, O4 and galactocerebroside (GalC) antibodies] was used to isolate G+D3O4- and O4+GalC- phenotypes directly from premyelinating cerebrum. In a basal defined culture medium, G+D3O4- progenitors differentiated infrequently into oligodendrocytes on a growth substratum comprised of meningeal cell-derived extracellular matrix. Their conversion into astrocytes, as determined by immunofluorescence analysis of glial fibrillary acidic protein expression, was induced by oncostatin-M as well as leukemia inhibitory factor (LIF) and ciliary neurotrophic factor, but not interleukin-6, and required extracellular matrix. By comparison, O4+GalC- progenitors were refractory to astrocyte induction under these conditions, as in short-term cultures of optic nerve, and differentiated into myelinogenic oligodendrocytes instead. Only in response to an overriding stimulus in fetal bovine serum did O4+GalC- progenitors, like their immediate precursors, become astrocytic. These data functionally distinguish two classes of astrocyte-inducing agents to provide clear evidence of an oligodendroblast, a progenitor defined by surface phenotype (O4+GalC-) and an altered response of the oligodendrocyte lineage to cytokines using signal transducer LIFR beta. PMID- 7875382 TI - Gated migration: neurons migrate on but not onto substrates containing S-laminin. AB - Components of the extracellular matrix influence migration of diverse cell types. Some, such as laminin, promote neuronal migration, whereas others are nonpermissive or inhibitory. Here, we demonstrate that a recombinant fragment of s-laminin, a homologue of the laminin B1 chain, is a barrier to neuronal migration. NSC-34 (motoneuron-like) and ciliary ganglion cells were plated on substrates coated with alternating stripes of laminin and a mixture of laminin plus s-laminin. On these patterned substrates, cells seldom crossed from s laminin-free to s-laminin-containing regions. Mutation of the tripeptide LRE, an adhesive site in s-laminin, abolished s-laminin's ability to block border crossing. However, overall rates of migration were similar on the two substrates. This behavior contrasts with that of previously reported barrier molecules, which decreases rates of cell migration when mixed with permissive substrates. Instead, s-laminin appears to block cell migration through a "gating" mechanism that acts primarily at borders. PMID- 7875383 TI - FGF can induce outgrowth of somatic mesoderm both inside and outside of limb forming regions. AB - In the vertebrate embryo, only somatopleural cells in the limb-forming region are released from the mesodermal layer and undergo outgrowth from the embryonic body to form the limb bud. Molecular signals which regulate limb bud induction are unknown to date. In the present study we examined the ability of fibroblast growth factor (FGF) to induce limb bud formation in chicken embryos. A replication-defective retrovirus encoding FGF type 4 with a reporter, bacterial beta-galactosidase, was microinjected into lateral plate mesoderm inside and outside limb-forming regions. Effects of the ectopic and precocious expression of FGF were assessed at various stages after infection. Here we report that somatic mesodermal cells in both flanks and limb-forming regions can respond to FGF and induce limb bud-like outgrowth. The supernumerary limb bud induced within a limb forming region differentiated into extralimb structures. These results strongly suggest potential roles of FGF signaling for induction of limb bud formation. PMID- 7875384 TI - Experimental Biology 95th. Atlanta, Georgia, April 9-13, 1995. Abstracts, Part I. PMID- 7875385 TI - Experimental Biology 95th. Atlanta, Georgia, April 9-13, 1995. Abstracts, Part II. PMID- 7875386 TI - [Hepatitis C virus and autoimmunity: a relationship that remains to be established]. PMID- 7875387 TI - [Prevalence and significance of non-specific anti-organelle antibodies of the liver in chronic viral hepatitis C]. AB - OBJECTIVES: The aim of this study was to evaluate the prevalence and the clinical signification of non organ specific autoantibodies in chronic hepatitis C. METHODS: We studied retrospectively 158 consecutive patients (97 with chronic hepatitis C, 24 with chronic hepatitis B, 67 with alcoholic cirrhosis) and 100 blood-donors. RESULTS: The prevalence of anti-nuclear and anti-smooth muscle antibodies was lower in blood donors than in patients (P < 0.001), but was comparable among the 3 groups of patients. The anti-liver-kidney microsome type 1 antibodies were detected only in patients with chronic hepatitis C (6%). The serum gammaglobulin level was significantly higher in patients with hepatitis C and anti-nuclear antibody titers > or = 1/50. The anti-smooth muscle antibodies detected in patients with hepatitis C had no anti-actin specificity. The response to interferon was not related to the detection of non organ specific autoantibodies before treatment. CONCLUSION: Anti-nuclear or anti-smooth muscle antibodies are not characteristic of hepatitis C virus infection. PMID- 7875388 TI - [Prevalence and characteristics of anti-tissue antibodies in chronic hepatitis caused by hepatitis C virus]. AB - OBJECTIVES: The prevalence and significance of antiorganelle antibodies in the serum of patients with chronic hepatitis C is a subject of controversy. We studied prospectively these characteristics in patients with chronic hepatitis C. METHODS AND RESULTS: Among 156 patients (age: 55 +/- 14 years; 83 females), 30 (19%) had significant titers of antiorganelle antibodies: anti-nuclear antibodies in 18, anti-smooth muscle antibodies in 8 (no anti-actin or anti-vimentine subtypes), anti-LKM1 in 2, type 2 anti-mitochondrial antibodies in 2 patients. Anti-organelle antibodies were not detected in 126 patients. Patients with anti organelle antibodies were significantly older but no difference was found between the two groups for sex ratio, serum amino-transferases or gammaglobulins, histopathological liver activity or prevalence of lymphocytic sialadenitis. The presence of anti-organelle antibodies was not related to HLA phenotype, especially B8 DR3, or DR4. Response to alpha interferon, estimated by serum aminotransferase levels after six months of treatment, was the same in both groups. CONCLUSIONS: These results suggest that serum anti-organelle antibodies are prevalent in during chronic hepatitis C but do not indicate a distinct autoimmune mechanism. Furthermore, the typing of anti-smooth muscle antibodies might help distinguish chronic hepatitis C from type 1 autoimmune chronic hepatitis. PMID- 7875389 TI - [Pulmonary vascular disorders in chronic diseases of the liver]. PMID- 7875390 TI - [Hepatitis C and immunologic anomalies]. PMID- 7875391 TI - [Hepatobiliary complications induced by cephalosporins]. PMID- 7875392 TI - Detection of bile acid malabsorption by the SeHCAT test. PMID- 7875393 TI - [Rate of alcohol abstinence in patients with chronic alcoholic pancreatitis]. AB - OBJECTIVES AND METHODS: The influence of clinical manifestations of alcoholic chronic pancreatitis on the continuation of alcohol intake is still poorly known. The aim was to study the number of patients who stop drinking alcohol and the factors favouring abstinence in 87 patients with alcoholic chronic pancreatitis and to compare them to 59 patients with alcoholic liver disease. Alcoholic abstinence was assessed by patient and relative questionnaire and by blood GGT dosage. RESULTS: The proportion of patients who became abstinent was higher in patients followed at least one year with alcoholic chronic pancreatitis (64%) than in patients with alcoholic liver disease (32%, P < 0.005). Patients mainly withdraw from alcohol in the first year after clinical onset of pancreatitis. The rate of abstinent patients was higher in patients who had presented an acute bout of alcoholic pancreatitis, in patients operated on and in patients with good social status. CONCLUSIONS: Patients with alcoholic chronic pancreatitis frequently withdraw from alcohol, mainly soon after clinical onset of the pancreatitis. This seems to be due to clinical manifestations of the pancreatitis. PMID- 7875394 TI - Combined magnetic resonance imaging and spectrometry for characterization of human pancreatic adenocarcinoma (Capan-1) heterotransplanted in nude mice. AB - Human pancreatic cancer cells (Capan-1 cell line) were heterotransplanted subcutaneously into nude mice. The resulting macroscopically visible tumours were analyzed by proton nuclear magnetic resonance spectrometry in a search for characteristic parameters. The Capan-1 xenografts were visualized by nuclear magnetic resonance imaging and were characterized by a significantly increased transverse relaxation time T2 (125 +/- 32 ms) compared with that recorded from ex vivo healthy human pancreatic tissue (60 +/- 11 ms). Three characteristic signals at 2.73, 3.23 and 3.5 ppm were observed by nuclear magnetic resonance spectrometry. They corresponded to unsaturated fatty acids, phosphatidylcholine, glycerophosphorylcholine and/or taurine respectively. These peaks were not observed in the spectra recorded from healthy human or mouse pancreas. On the basis of these parameters, small intraperitoneal Capan-1 xenografts (less than 0.5 cm diam), which were only visible at the macroscopic level after opening the abdominal cavity, were accurately localized by magnetic resonance imaging and spectrometry. PMID- 7875395 TI - [Measurement of ileal absorption of bile salts with the selenium 75 labelled homotaurocholic acid test. Validation and clinical significance]. AB - OBJECTIVES AND METHODS: The performances and the clinical significance of a simplified version of the 75SeHCAT test which measures ileal absorption of bile salts were assessed in 23 healthy subjects and 106 patients. Corporeal retention of the marker was measured using an uncollimated gamma-camera. RESULTS: In healthy subjects, the 75SeHCAT retention was lower in the group of 9 with an osmotic diarrhoea induced by a PEG solution than in the group of 14 tested in normal conditions (22 +/- 4% vs 44 +/- 4%; P < 0.01). The reproducibility of the measure was good (r = 0.93; P < 0.001). The sensibility and specificity of the test for the diagnosis of ileal involvement were 79% and 90% respectively. Bile acid malabsorption was evidenced in 38% of patients with functional diarrhoea (59% and 28% in patients with and without previous cholecystectomy respectively; P < 0.02). In patients with fonctional diarrhoea, a correlation was evidenced between the orofaecal transit time and the 75SeHCAT retention (r = 0.66; P < 0.001) and cholestyramine improved diarrhoea in 8 out of 11 patients with 75SeHCAT malabsorption and in 2 out of 5 patients with normal test. These results show that the 75SeHCAT test is accurate and that bile acid malabsorption, frequently evidenced in functional diarrhoea, is correlated with an acceleration of intestinal transit. PMID- 7875396 TI - [Entero-enteral fistulas in Crohn disease: radical or conservative surgical treatment of the "victim" segment?]. AB - OBJECTIVES AND METHODS: Entero-enteral fistulas join a segment affected by Crohn's disease to another which becomes a drainage route and a "victim" of the process. Surgical treatment can be radical (extensive resection of both segments) or conservative (resection of involved bowel and conservation of the "victim"). Fifty-nine patients operated on for Crohn's disease and having 80 entero-enteral fistulas were retrospectively studied. RESULTS: Main surgical indications were symptomatic intestinal stenosis (56%) or abdominal mass (20%) unresponsive to medical treatment. Fistula was discovered during operation in 33 patients (56%). Conservative treatment was performed in 39 fistulas (49%). In 41 fistulas (51%), proximity of fistulous ends, or Crohn's disease's extension, led to radical treatment. In 66 fistulas (82.5%), histologic examination revealed that Crohn's disease affected only one bowel segment, the other demonstrating only non specific features; in the 14 remaining fistulas (17.5%), Crohn's disease affected both segments. CONCLUSIONS: The clinical presentation of entero-enteral fistulas (non-specific symptoms, frequent peroperative diagnosis), their pathological features (victim segment often free of Crohn's disease) plead for a conservative surgical approach, i.e. adapted to real bowel involvement by Crohn's disease. PMID- 7875397 TI - [Pseudocysts of the pancreas. Natural history and therapeutic indications]. PMID- 7875398 TI - [Absence of subrenal inferior vena cava revealed by rupture of duodenal varices in an adult]. AB - This report concerns a case of absence of caudal inferior vena cava revealed by gastrointestinal bleeding from isolated duodenal varices by an adult. The diagnosis of duodenal varices was performed by ultrasonographic endoscopy. Development of duodenal varices in absence of portal hypertension is uncommon. Involvement of cavo-portal collateral circulation in case of inferior vena cava obstruction is unusual and duodenal varices are still more rarely encountered. Diagnosis was ultimately supported by femoral venous angiography showing the absence of inferior vena cava and a venous return from the right lumbar vein into the portal vein via the duodenal varices. The absence of caudal portion of inferior vena cava is more probably related to neo-natal thrombosis than to a true atresia. PMID- 7875399 TI - [Acute relapsing pancreatitis, revealing Crohn disease, and regressing under corticotherapy]. AB - A case of acute relapsing pancreatitis revealing Crohn's disease is reported. The diagnosis of chronic pancreatitis was highly suspected because of characteristic pain, repeated serum pancreatic enzyme elevation and ultrasound, CT-scan, pancreatography, and endosonography data. None of the classical aetiologies for chronic or acute pancreatitis were found. This observation presents some outstanding particularities: a) pancreatitis revealed Crohn's disease; b) there was no duodenal involvement by Crohn's disease; c) the diagnosis of chronic pancreatitis was highly suspected; d) corticoids induced dramatic improvement of intestinal and pancreatic manifestations, and the patient remained asymptomatic during a two-year follow-up. The efficacy of corticotherapy on pancreatic disorders suggests a common mechanism explaining the two diseases. PMID- 7875400 TI - [Acute toxoplasmic pancreatitis. An unusual cause of death in AIDS]. AB - We report a case of an acute toxoplasmic pancreatitis that led to the death of an AIDS patient. Aetiological diagnosis was performed by the post mortem histological examination. On haematein-eosin staining, toxoplasmic cysts and pseudocysts were noted in the pancreatic acini. Immunohistochemical study using anti-Toxoplasma gondii polyclonal antibodies showed free parasitic forms or tachyzoites in the necrotic areas. Toxoplasmic cysts without any inflammatory reaction were observed in the lungs. In the acquired immunodeficiency syndrome, involvement of the pancreas by toxoplasmosis is very rare and associated with a multivisceral dissemination. Even if this diagnosis is exceptional, acute toxoplasmic pancreatitis must be considered in an AIDS patient when the other causes of pancreatitis, as drugs or infectious diseases, have been eliminated. PMID- 7875401 TI - [Nodular regenerative hyperplasia of the liver and Turner syndrome]. PMID- 7875402 TI - [Decrease of cholesterolemia and apolipoprotein B in chronic viral hepatitis C with massive steatosis]. PMID- 7875403 TI - [Hemobilia revealing calculosis and cancer of the gallbladder. Value of retrograde choledocoscopy]. PMID- 7875404 TI - [Hepatocellular adenoma in a woman following administration of danazol]. PMID- 7875405 TI - [A new case of hepatitis after alpidem monotherapy]. PMID- 7875407 TI - [Subacute De Quervain's thyroiditis revealing viral hepatitis A]. PMID- 7875408 TI - [Muscular metastasis from a gastric adenocarcinoma]. PMID- 7875406 TI - [Severe hepatitis caused by phenobarbital]. PMID- 7875409 TI - [Non-alcoholic chronic pancreatitis: should the mutation delta F508 of the CFTR gene be considered as a risk factor?]. PMID- 7875410 TI - [Chronic pancreatitis associated with pancreas divisum in a patient on imcomplete abdominal situs inversus]. PMID- 7875411 TI - [Acute pancreatitis induced by valproic acid]. PMID- 7875413 TI - [Liver fibrosis. Current concepts]. PMID- 7875412 TI - [Eosinophil pleurisy revealing carcinoid tumor (2 cases)]. PMID- 7875414 TI - Limy bile. A surgical experience in 16 patients. AB - OBJECTIVES: This study is a retrospective analysis of clinical symptoms and operative findings in 16 patients with limy bile (mean age: 47.3 years, M/F ratio: 1/7) operated on over a 25-year period. METHODS: The patients were separated into two groups: patients with limy bile limited to the gallbladder and those with limy bile extending to the common bile duct. RESULTS: In the group of patients with limy bile in the gallbladder (n = 11), previous attacks of biliary pain were present in 9 and the gallbladder was entirely inactive in 9; an elective cholecystectomy was performed; an impacted stone was found in the neck of the gallbladder (n = 5) or in the cystic duct (n = 6), and the intraoperative cholangiogram was normal. The material deposited in the gallbladder was characteristically creamy or dense, white or yellow-brown, and consisted of calcium carbonate. The patients with limy bile extending to the common duct (n = 5) were admitted with acute pain and jaundice, and operated on a few days later. In the common bile duct, limy bile was associated with small stones (n = 4). CONCLUSION: Abdominal radiographs are sufficient to identify limy bile. The presence of this condition in the gallbladder is always associated with biliary lithiasis and the obstruction of the cystic duct. The presence of limy bile in the common bile duct is due to the migration of impacted stone and calcareous material deposited in from the gallbladder. Surgical treatment is only necessary in patients with specific biliary symptoms. PMID- 7875415 TI - [Extracellular matrix of the liver: structure and regulation]. PMID- 7875417 TI - [Hepatotoxicity of drugs. Seventh update of the bibliographic database of liver lesions and related drugs]. PMID- 7875416 TI - [Effects of atrial natriuretic factor on renal excretion of sodium in patients with liver cirrhosis]. PMID- 7875418 TI - [Cytoprotection in 1994: twenty years later]. PMID- 7875419 TI - [Effect of enprostil on the healing and the recurrence of duodenal ulcer. Comparison with ranitidine]. AB - Enprostil, a synthetic prostaglandin E2, has been shown to exert both antisecretory and mucoprotective activity. It is effective in duodenal ulcer healing. OBJECTIVE--This study was performed to compare the frequency and the delay of spontaneous duodenal ulcer relapse during a two-year follow up period after initial healing by enprostil (35 micrograms, twice a day) or ranitidine (300 mg per day). METHODS--This multicentric, double-blind, randomized study included 642 patients (324 in the enprostil group and 318 in the ranitidine group). Patients included in the follow up period were evaluated by an endoscopy at 6 months, one and two years after healing. RESULTS--After a 6 weeks treatment period, healing rate was 85% for ranitidine and 70% for enprostil, respectively (P < 0.001). Adverse effects, especially digestive ones, occurred more often with enprostil than with ranitidine (P < 0.001). After initial healing, there was no significant difference between the 2 groups concerning the cumulative rate of relapse, despite a non significant trend for a milder rate of relapse in the enprostil group (P = 0.08). Twenty-seven % of the patients randomized to treatment (intend-to-treat analysis) in the enprostil group and 29% in the ranitidine group had no ulcer recurrence 6 months after ulcer healing, and respectively 12% and 13% at 2 years (difference not statistically significant). CONCLUSIONS--It is concluded that a) ranitidine is more effective and has less adverse effects than enprostil for duodenal ulcer healing, b) after duodenal ulcer healing by enprostil, there is a non significant trend for a lower rate of relapse than after healing with ranitidine, c) there is the same proportion of patients without ulcer in the 2 groups after 6 months and 2 years. PMID- 7875420 TI - [Variations of plasma gastrin (basal and postprandial) in ththtreatmentof duodenal ulcer with either enprostil or ranitidine. Correlations with rates of relapse]. AB - Enprostil, a synthetic E2-prostaglandin efficacious for duodenal ulcer healing, presents both antisecretory and antigastrinic effects. This is at variance with the elevation of plasma gastrin observed with ranitidine. OBJECTIVE--This leads us to compare enprostil and ranitidine on the following points: a) variations of plasma gastrin (basal and postprandial) parameters over a 6-week conventional treatment; b) correlation studies between ulcer relapses (frequency and temporal evolution) after treatment discontinuation and various gastrinic criteria. METHODS--Among a group of 642 patients followed for ulcer relapse, 165 were considered for gastrin (78 of the "Enprostil" group and 87 of the "Ranitidine" group). RESULTS--Initially, both populations were comparable for clinical and plasma gastrin parameters. After 6 weeks of treatment, the increases in the various gastrin parameters (basal, postprandial, peak, integraded) were significantly greater and the absolute values higher (Wilcoxon, P < 0.001) with ranitidine than with enprostil. No correlation was found between relapse occurrence after drug discontinuation and these gastrin parameters. CONCLUSIONS- Ranitidine hypergastrinemia seems directly related to gastric hyposecretion whereas its absence with enprostil is likely more dependent upon a specific antigastrinic activity than on a reduced antisecretory activity. Those differences in mechanism of action have no consequence on the stability of ulcer obtained by either drug. PMID- 7875421 TI - [Expression of laminin is correlated to the differentiation of human colonic cancer cells]. AB - The level and molecular composition of laminin, a major basement membrane glycoprotein formed of three chains (A, B1 and B2) have been analyzed in various human colonic cancer cells (Caco-2 and HT29). The synthesis of laminin over a 24 h period, corresponding to cellular and secreted molecules purified by affinity chromatography, was the highest in the more differentiated cells. Immunocytochemical detection of the constituent chains of laminin in permeabilized cells as well as after separation on polyacrylamide gels showed that A, B1 and B2 chains were expressed in Caco-2 cells, whereas A chain was not detected in HT29 cells. When cancer cells were cultured on a monolayer of confluent fibroblastic cells, laminin was deposited at the basement membrane level only in the case of the most differentiated cells. In an attempt to define the role of laminin-A chain, transfection of Caco-2 cells with A chain antisense cDNA was performed; among the clones obtained, 3 were deficient for the target polypeptide. The consequences of the absence of laminin-A chain on basement membrane formation, cellular differentiation and tumor invasion will be currently determined. PMID- 7875422 TI - [Study of intestinal permeability in man]. PMID- 7875423 TI - [Vascular gastric anomalies, CREST syndrome and primary biliary cirrhosis: efficacy of ethinyl estradiol-norethisterone combination]. AB - Vascular gastric lesions are a rare cause of chronic gastric bleeding. We report the case of a 70-year old woman with primary biliary cirrhosis, CREST syndrome and vascular gastric lesions corresponding to watermelon stomach. Oestrogen progesterone treatment successfully controlled recurrent blood loss. PMID- 7875424 TI - [Subcutaneous seeding on the tract of percutaneous cytologic puncture with a fine needle of a hepatic metastasis from colonic adenocarcinoma]. AB - Subcutaneous seeding after percutaneous ultrasonically guided fine needle aspiration of liver tumours is a rare complication and only a few cases have been reported. We report a new case of cutaneous implantation following a fine needle (21.5 gauge of external diameter) aspiration biopsy of a superficial colonic liver metastasis, as shown by a subcutaneous nodule and increased serum carcinoembryonnary-antigen. We discuss the risk factors of this rare complication, especially the thickness of the liver parenchyma along the needle tract and precautions which can be taken for prevention. PMID- 7875425 TI - [Necrotizing amebic colitis]. AB - We report a case of necrotizing amebic colitis in a 43 year-old patient, 10 years after a stay in Senegal, successfully treated by right hemicolectomy. Entamoeba histolytica were found in colon necrosis and amoebiasis serology was positive, leading to the diagnosis. The epidemiologic, physiopathologic, clinical and therapeutic features of this exceptional affection are described. A few cases have been previously reported in non endemic areas where pre-operative diagnosis is rarely made. In endemic areas, a conservative treatment by ileostomy and colonic lavage seems to reduce the death rate. PMID- 7875426 TI - [Porphyria cutanea tarda appearing during prolonged viral hepatitis A]. PMID- 7875427 TI - [Nasobiliary aspiration in the treatment of postoperative biliary fistula]. PMID- 7875428 TI - [Endoscopic intubation of esophageal tumoral stenoses with a metallic self expanding stent. Clinical study of 22 patients]. PMID- 7875429 TI - [Treatment of severe gastroduodenal hemorrhages with the analog of somatostatin (octreotide: SMS 201-995)]. PMID- 7875430 TI - [Cystic tumors and an endocrine tumor of the pancreas: an unusual association]. PMID- 7875431 TI - [Isolated peritonitis: a rare form of eosinophilic gastroenteritis]. PMID- 7875432 TI - [Endoscopic ligation or endoscopic sclerotherapy in the treatment of hemorrhages caused by rupture of esophageal varices?]. PMID- 7875433 TI - [Acid secretory rebound after gastric antisecretory treatment. Above all, a problem for the physiologists!]. PMID- 7875434 TI - [Treatment of caustic burns of the esophagus with interferon gamma. Comparison with epidermal growth factor. Experimental study in rats]. AB - OBJECTIVES: Effects of sequential use of epidermal growth factor followed by interferon gamma on healing response after severe oesophageal corrosive burns has been demonstrated. This sequential treatment improves the inflammatory response of the initial phase and prevents residual stenosis. The aim of this study was to evaluate the use of interferon gamma alone in the same condition. METHODS: The study was performed in 5 groups (n = 15) of Wistar rats: control, placebo, epidermal growth factor alone, interferon gamma alone and epidermal growth factor for 5 days followed by interferon gamma from the 6th to 20th day. The last 4 groups had an oesophageal injury caused by a solution of 2.5 N NaOH. The efficacy of treatment was assessed on days 2, 5 and 20 on: weight gain, oesophageal internal lumen, stenosis index: wall thickness/lumen diameter, collagen production. RESULTS: Interferon gamma significantly reduced residual stenosis frequency while it did not improves the initial healing process. A complete effect on the two healing phases was only observed in animals having the sequential treatment. CONCLUSIONS: These results could lead to clinical trial in man to evaluate efficacy of sequential treatment with epidermal growth factor interferon gamma in oesophageal corrosive burns. PMID- 7875435 TI - [Sensitivity of gastric parietal cells to histamine after administration of enprostil and ranitidine during 4 weeks in healthy subjects]. AB - Parietal cell sensitivity is increased in patients with active duodenal ulcer. It has been shown to increase in healthy volunteers after a 4-week treatment with H2 receptor blockers. Metaanalyses of therapeutic trials have indicated that time to first relapse was longer after ulcer healing with prostaglandins (PG) than after healing with H2-receptor blockers, which might be due to a different effect of the two treatments on parietal cell sensitivity. OBJECTIVES--To study, in healthy volunteers, basal gastric acid secretion, acid secretory responses and parietal cell sensitivity to histamine before and after a 4-week treatment with enprostil (E) and ranitidine (R). METHODS--This was a randomized double-blind double-dummy crossover study. Twelve male healthy volunteers (22-44 years) were randomly assigned to receive a 4-week treatment with either E (35 micrograms bid) or R (150 mg bid). After a 2-month washout period, they were crossed to the alternate treatment. Basal acid output (BAO), acid secretory responses to low-dose histamine infusion (histamine dihydrochloride 2.5 micrograms/kg/h) (LDAO), to a high-dose histamine infusion (25 micrograms/kg/h) (HDAO) and parietal cell sensitivity (PCS = LDAO/HDAO x 100) were measured 24 hours before the first administration and 72 hours after the last administration of each medication. RESULTS--All secretory parameters were similar before treatment with E and R. As compared to pretreatment values: a) HDAO tended to increase after both treatments (NS); b) LDAO (m +/- sem) slightly increased after R (18.4 +/- 2.6 vs 13.9 +/- 3.3 mEq) (NS) but not after E (12.5 +/- 1.8 vs 13.2 +/- 1.9 mEq); c) PCS (m +/- sem) was unchanged after R (36 +/- 4 vs 33 +/- 6) but decreased after R (30 +/- 6 vs 36 +/- 0.5; P < 0.02). When secretory parameters after treatment with R and treatment with E were compared, the difference was significant for LDAO (P < 0.02) and PCS (P < 0.05). CONCLUSIONS--If also found in patients with duodenal ulcer disease, these results might, at least partly, explain the lesser propensity of the ulcers to relapse early after healing with PG than after healing with H2-receptor blockers. However enprostil has been with-drawn from the market and it is now well established that one factor influencing the relapse rate is the efficiency of the treatment given to achieve ulcer healing in eradicating Helicobacter pylori. Consequently, the interest of our results is presently mostly physiological. PMID- 7875436 TI - [Comparative efficacy of lansoprazole and omeprazole on the intragastric pH measured over a period of 24 hours and on the basal]. AB - OBJECTIVES: This paper aimed at evaluating the comparative efficacy of lansoprazole and omeprazole in reducing gastric acid secretion in patients suffering from Zollinger-Ellison syndrome. METHODS: Nine patients with non resected gastrinoma(s) an previously well controlled by omeprazole (mean dosage 75 +/- 12.4 (SEM) mg/day; extremes: 20-160 mg/day) underwent 24-hour intragastric pH-metry, baseline acid output before next dosing and serum gastrin dosages, receiving their usual therapy and thereafter lansoprazole at a weight equivalent posology (mean dosage 81.6 +/- 12.5 (SEM) mg/day; extremes: 30-165 mg/day). RESULTS: Lansoprazole maintained intragastric pH and basal acid output at therapeutic levels, but a discrete reacidification, that deserves confirmation on a larger group of patients, was observed between the meals. CONCLUSIONS: The possible long-term benefit of this phenomenon, especially on gastrinemia and the fundic ECL-cells density and gastric bacterial content, remains to be evaluated. PMID- 7875437 TI - [Effect of C-terminal derivatives of sorbin on ileal ion transport stimulated by VIP in rats]. AB - OBJECTIVES AND METHODS: Sorbin, a peptide isolated from porcine intestine and composed of 153 aminoacids, has been purified because its specific action is to increase water and ion absorption in the intestine and the gall bladder. We showed that synthetic peptides containing the amidated C-terminal part of sorbin had the same activity as the natural molecule in increasing duodenal absorption. In order to characterize the site of action of sorbin, the effect of two C terminal derivatives were determined in ileal ligated loops in situ in anaesthetised rats, following VIP-induced water and electrolyte secretions. Their effect was compared to those of metenkephalinamide, NPY and somatostatin. Unidirectional fluxes were studied to analyze the mechanism of action of sorbin, by means of 22Na, administered into the intestinal loop, and 36Cl, injected into blood. RESULTS: Results show that C20-sorbin and C7-sorbin decreased the VIP stimulated net flux of water (inhibition of 40 and 37%, respectively), Na (inhibition of 31 and 30%), C1 (inhibition of 80 and 63%) and HCO3 (inhibition of 15 and 25%). These effects are evidently greater than those produced by equimolar doses of NPY, somatostatin, and 32 times higher dose of metenkephalinamide. Sorbin acts as a potent anti-secretor, anti-VIP, in rat ileum. PMID- 7875439 TI - [Adjuvant treatment of cancers of the esophagus]. PMID- 7875438 TI - [Adjuvant treatments in digestive cancers. General principles]. PMID- 7875440 TI - [Adjuvant treatment of colorectal cancers]. PMID- 7875441 TI - [Modifiers of the biological response in the adjuvant treatment of digestive cancers]. PMID- 7875442 TI - [Adjuvant treatment of cancers of the stomach]. PMID- 7875443 TI - [Adjuvant treatment of endocrine digestive tumors]. PMID- 7875444 TI - [Vasopressin, somatostatin and digestive hemorrhages in portal hypertension: the end of the tunnel?]. PMID- 7875445 TI - [Cholestatic viral hepatitis A in adults. Clinical, biological and histopathological study of 9 cases]. AB - OBJECTIVES: We report here 9 cases of acute viral hepatitis A leading to hospitalization between June 1989 and October 1992. The main feature was a marked and protracted cholestasis. RESULTS: Jaundice lasted an average of 77 +/- 39 days (range: 30-120) and total serum bilirubin concentrations were 265 +/- 184 mumol/L (range: 51-560). IgM anti-HAV was present in the serum for 6.3 +/- 5.5 months (median: 4, range: 2-19). Histopathological examination of the liver was performed in 6 patients and most showed intralobular cholestasis and portal tract inflammation associated with dystrophy and paucity of bile ducts. Acute renal failure was noted in one patient. In three patients, whose pruritus was not relieved by cholestyramine, plasma exchange was an effective therapy. CONCLUSION: These case reports confirm the severity of viral hepatitis A in adults and emphasize the importance of vaccination. PMID- 7875446 TI - [Efficacy and mode of action of vasopressin in the treatment of digestive hemorrhages caused by rupture of esophageal or gastric varices]. PMID- 7875447 TI - [Somatostatin, octreotide and portal hypertension]. PMID- 7875448 TI - [Liver in normal pregnancy]. PMID- 7875449 TI - [Exudative gastropathy associated with cytomegalovirus infection after allogenic bone marrow transplantation]. AB - The authors report a case of protein losing gastropathy associated with cytomegalovirus. This form which is extremely rare in adults occurred alone after allogenic bone marrow transplantation and become apparent by a hypoalbuminaemia causing oedema of the lower limbs. Gastrocopy showed large red folds of approximately a centimetre covered in a whitish hypersecretion coating. Biopsy demonstrated active gastritis which appeared on a hypertrophic and hypersecretive gastritis. Outcome was favourable within 3 months without treatment. PMID- 7875450 TI - [Colonic lymphoma simulating cryptogenetic colitis associated with common variable hypogammaglobulinemia]. AB - We report the case of a 72 year-old woman with late-onset common variable immunoglobulin deficiency who was hospitalized for diarrhoea and fever. Colonoscopy showed aphtoid and deep ulcerations in the rectum, the sigmoid and transverse colon, suggestive of Crohn's disease. Histologic and immunohistochemical study revealed a low grade B cell mucosa-associated lymphoid tissue (MALT) lymphoma. This is an unusual presentation for colonic lymphoma, and the second case of colonic lymphoma associated with late-onset common variable immunoglobulin deficiency. PMID- 7875451 TI - [Pericarditis during inflammatory bowel diseases. Extra-intestinal or iatrogenic complication?]. AB - Acute pericarditis is rarely associated with inflammatory bowel disease. In such cases, when usual aetiologies have been excluded, pericarditis can be considered to be either an extraintestinal manifestation of inflammatory bowel disease or due to an adverse drug effect. We report a case of acute pericarditis in a 17 year old patient with ulcerative colitis treated with mesalazine for 15 days. Mesalazine was discontinued with a prompt and spontaneous resolution of the symptoms. Extensive investigations revealed no known cause for his pericarditis. Eight days and 75 days after the diagnosis, a lymphoblastic transformation test in the presence of mesalazine was performed and was positive for concentration greater than or equal to 10 micrograms/mL; this test was negative in 3 control patients treated with mesalazine without adverse drug effect. This observation together with the rare documented cases allows to consider the possibility that pericarditis may be caused by an adverse drug reaction in these patients. PMID- 7875453 TI - [Scurvy in Paris in 1994 in a drinker of milk with gastroesophageal reflux]. PMID- 7875452 TI - Fatal hemobilia after liver graft biopsy in a transplanted child. AB - Severe hemobilia after liver transplantation is a rare complication. We report one case of fatal hemobilia resulting from arterio-biliary fistula after a liver graft needle biopsy in a 7-year-old girl transplanted with a reduced-size graft. Arterial reconstruction was performed by an iliac conduit implanted in the aorta. The diagnosis of hemobilia was made by angiography but the hemorrhage could not be controlled by selective embolization of the bleeding arterial branch. The patient died from early and massive recurrent bleeding before surgery. The prevention of iatrogenic hemobilia and current therapeutic strategies are discussed. PMID- 7875454 TI - [Intra-endoscopic unshackling of an esophageal self-expanding metal implant]. PMID- 7875455 TI - [Procedures of decontamination used in centers of digestive endoscopy in Gironde: new evaluation at distance]. PMID- 7875456 TI - [A desmoid tumor sensitive to hormonotherapy]. PMID- 7875457 TI - [Proctorrhagia due to portal colonopathy and treated by surgical portacaval anastomosis]. PMID- 7875458 TI - [Advanced liver cirrhosis secondary to heterozygote alpha 1-antitrypsin deficiency in a young woman: treatment by liver transplantation]. PMID- 7875459 TI - [Esophageal candidiasis during interferon therapy for chronic viral hepatitis C]. PMID- 7875460 TI - [Infection of ascitic fluid caused by Campylobacter jejuni in a patient with liver cirrhosis. A new case with an atypical presentation]. PMID- 7875461 TI - [Acute toxoplasmic hepatitis in a non immunosuppressed patient]. PMID- 7875462 TI - [Predictive factors of total destruction of a rectal cancer treated with laser. Contribution of ultrasound endoscopy]. PMID- 7875463 TI - [Localization and physiopathological role of protein-acetaldehyde complexes in hepatocytes]. PMID- 7875464 TI - [Value of intra-endoscopic cytology for the diagnosis of biliopancreatic stenosis]. PMID- 7875465 TI - Inefficacy of intestinal secretory immune response to Cryptosporidium in acquired immunodeficiency syndrome. AB - BACKGROUND/AIMS: An alteration of the secretory immune response has been forwarded to explain frequent and chronic mucosal infections in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to explore the intestinal immunoglobulin (Ig) secretions in patients with AIDS and their relationships to cryptosporidiosis. METHODS: Patients with AIDS and enteric cryptosporidiosis (n = 12), other enteric infections (n = 10), and no identifiable enteric pathogen (n = 10) and human immunodeficiency virus seronegative controls (n = 18) were studied. The number of intestinal IgA and IgM plasma cells of the duodenal lamina propria mucosa and total and anti Cryptosporidium IgA, IgM, and IgG were measured in serum and feces. RESULTS: Although not significantly increased, the number of IgA and IgM plasma cells was greater in patients with AIDS (n = 20) than in controls (n = 5). In feces, total IgA outputs and specific anti-Cryptosporidium IgA levels were significantly higher in patients with AIDS and cryptosporidiosis than in the two other groups of patients with AIDS (P < 0.05 and P < 0.01, respectively) and controls (P < 0.001 and P < 0.01, respectively). Total fecal IgM output and specific anti Cryptosporidium IgM coproantibodies were increased only in the Cryptosporidium infected patients relative to the controls (P < 0.05). CONCLUSIONS: Despite the development of pathogen-specific mucosal antibody responses, patients with AIDS and cryptosporidiosis fail to clear the parasite. PMID- 7875466 TI - Selective dysfunction of mechanosensitive intestinal afferents in irritable bowel syndrome. AB - BACKGROUND/AIMS: Experimental studies have shown gut hypersensitivity in irritable bowel syndrome. The aim of this study was to determine whether heightened perception of gut distention in irritable bowel syndrome is related to either decreased gut compliance, altered mechanosensitive afferents, or nonspecific sensory dysfunction. METHODS: In 17 patients with irritable bowel syndrome and 15 healthy controls, stimulus-related perception of (1) intestinal balloon distentions, (2) transmucosal electrical nerve stimulation (15 Hz, 100 microseconds), and (3) somatic transcutaneous electrical nerve stimulation (100 Hz, 100 microseconds) was measured. Individual stimuli of 1-minute duration were randomly applied at 5-minute intervals. RESULTS: Patients tolerated smaller intestinal volumes than controls (33 +/- 3 mL vs. 43 +/- 4 mL, respectively; mean +/- SE; P < 0.05), whereas both intestinal compliance and perception of transmucosal electrical nerve stimulation were normal (patients tolerated 58 +/- 5 mA and healthy subjects tolerated 69 +/- 5 mA). Interestingly, patients perceived both stimuli more diffusely than controls; 48% +/- 9% distentions and 52% +/- 9% electrical stimuli were perceived over more than one abdominal region vs. 21% +/- 9% and 18% +/- 6%, respectively, in controls (P < 0.05 for both). In contrast to gut distentions, patients showed higher tolerance of somatic stimuli than controls (68 +/- 7 mA vs. 42 +/- 6 mA, respectively; P < 0.05). CONCLUSIONS: Patients with irritable bowel syndrome show selective hypersensitivity of intestinal mechanosensitive pathways associated with a nonspecific, probably central dysfunction of viscerosomatic referral. PMID- 7875467 TI - Regulation of interleukin-8 production in a human colon epithelial cell line (HT 29). AB - BACKGROUND/AIMS: Interleukin (IL) 8 is a major neutrophil-activating cytokine synthesized by intestinal epithelial cell lines. The aim of this study was to improve the understanding of the regulation of IL-8 synthesis by investigating the roles of protein kinase C (PKC), protein kinase A (PKA), and protein tyrosine kinase (PTK) in the induction of IL-8. METHODS: HT-29 cells were stimulated with IL-1 beta or tumor necrosis factor alpha (TNF-alpha) together with activators or inhibitors of PKC and PKA or with inhibitors of PTK. The presence of IL-8 protein was detected by enzyme-linked immunosorbent assay and that of IL-8 messenger RNA by Northern blotting and in situ hybridization. RESULTS: TNF-alpha and IL-1 beta dose-dependently induced IL-8 production in HT-29 cells. Activation of PKC by phorbol myristate acetate also stimulated IL-8 production; however, the effects of IL-1 beta or TNF-alpha did not require PKC, as shown by the PKC inhibitor staurosporin or PKC depletion. Stimulation of PKA by forskolin or inhibition by H89 or H7 had no influence on the synthesis of IL-8. However, induction of IL-8 by IL-1 beta or TNF-alpha was reduced by the PTK inhibitors herbimycin (by 79% or 89%, respectively) and genistein (by > 95%). CONCLUSIONS: The synthesis of IL-8 is stimulated in HT-29 cells by IL-1 beta or TNF-alpha. This stimulation is independent from PKC or PKA but depends on protein tyrosine phosphorylation. PMID- 7875468 TI - Effect of HCl on transmembrane potentials and intracellular pH in rabbit esophageal epithelium. AB - BACKGROUND/AIMS: Acidification of the basolateral membrane by adding HCl to the serosal solution of esophageal epithelium leads to more necrosis than acidification of the apical membrane by adding HCl to the luminal solution. The aim of this study was to examine the mechanism for this difference. METHODS: The effect of low extracellular pH (pHo) (HCl) on intracellular pH (pHi) and transmembrane potentials was examined in rabbit esophageal cells by impalement with intracellular microelectrodes. RESULTS: Lowering luminal pH to 3.0 had no effect on membrane voltage and/or pHi in either luminally or serosally impaled cells, although a decline in both parameters occurred at pH 1.5 in luminally impaled cells. In contrast, lowering serosal pH from 7.4 to 3.0 progressively reduced membrane voltage and/or pHi. Membrane depolarization at low pHo was inhibited by a high-potassium solution or barium and mimicked by lowering pHi (gassing with CO2) at neutral pHo. CONCLUSIONS: Basolateral, but not apical, membranes of esophageal epithelial cells are highly permeable to H+, accounting for the greater susceptibility to damage from exposure to serosal than luminal acid. Membrane depolarization at low pHo is mediated by low pHi through inhibition of basolateral membrane K+ conductance. PMID- 7875469 TI - Mercaptopropionate inhibits butyrate uptake in isolated apical membrane vesicles of the rat distal colon. AB - BACKGROUND/AIMS: Previous observations have shown that mercapto- and bromo- short chain fatty acids diminish fatty acid use in colonic epithelium. The aim of this study was to investigate whether this effect is attributable to the inhibition of short-chain fatty acid uptake. METHODS: Apical membrane vesicles of rat colonocytes were prepared by a discontinuous sucrose gradient after isolation of membrane caps. [14C]butyrate uptake was measured by rapid filtration technique. RESULTS: Preloading of isolated apical membrane vesicles with bicarbonate or butyrate stimulated [14C]butyrate uptake and resulted in up to fivefold overshoots. Increasing extravesicular butyrate concentrations saturated the bicarbonate-stimulated butyrate uptake with a binding constant of 44.7 +/- 5.9 mmol/L and a maximum velocity of 33.2 +/- 2.7 nmol.mg protein-1.3 s-1. Intravesicular butyrate uptake was inhibited by addition of 20 mmol/L 3 mercaptopropionate (43.0% +/- 5.6%), whereas 2-bromo-propionate (13.9% +/- 4.1%) and 4-bromobutyrate (22.6% +/- 5.3%) did not significantly alter butyrate uptake. Increasing concentrations of 3-mercaptopropionate had a competitive inhibitory effect on butyrate uptake with a binding constant following inhibition of 6.25 +/ 0.87 mmol/L and a maximum velocity of 5.82 +/- 1.01 nmol.mg protein-1.3 s-1. CONCLUSIONS: Butyrate uptake in apical membrane vesicles of rat distal colon is mediated by a low-affinity anion transport system, which can be competitively inhibited by 3-mercaptopropionate but not by 2-bromopropionate and 4 bromobutyrate. PMID- 7875470 TI - The sympathetic nervous system modulates perception and reflex responses to gut distention in humans. AB - BACKGROUND/AIMS: Intestinal distention induces perception and gut reflexes via sympathetic and vagal pathways, but the modulatory mechanisms of such responses remain obscure. The aim of this study was to determine the effects of sympathetic nervous activity on sympathetic and vagal reflexes as well as on intestinal and somatic perception. METHODS: In 9 healthy volunteers, proximal duodenal distentions were produced in 4-mL increments and hand transcutaneous electrical nerve stimulation was produced in 3-mA increments. Increasing stimuli of 1-minute duration were randomly performed at 10-minute intervals both with and without sympathetic activation (induced by means of lower body negative pressure). Intestinal and somatic perception was scored by specific questionnaires; vagal enterogastric and sympathetic intestinointestinal relaxatory reflexes were simultaneously measured by gastric and distal duodenal barostats. RESULTS: Sympathetic activation significantly heightened perception of intestinal distention without modifying perception of somatic stimuli (perception scores increased by 41% and -2%, respectively). The reflex responses to duodenal distention significantly increased during sympathetic activation both in the stomach and in the intestine (relaxation increased by 91% and 69%, respectively; P < 0.05 for both). CONCLUSIONS: Activation of the sympathetic nervous system selectively increases visceral but not somatic sensitivity and enhances both vagally and sympathetically driven reflexes in the gut. PMID- 7875471 TI - Differential in vivo and in vitro intestinal permeability to lactulose and mannitol in animals and humans: a hypothesis. AB - BACKGROUND/AIMS: Clinical interpretation of urinary recovery ratios of lactulose and mannitol is hampered by incomplete understanding of the mechanisms of transmucosal passage. The aim of this study was to compare in vivo and in vitro probe permeability. METHODS: Stripped sheets of small intestine from rodents and human biopsy specimens were mounted in Ussing chambers, and mucosa-to-serosa fluxes of lactulose and mannitol were determined. Urinary recovery of orally applied probes was measured in rodents, cats, and humans. RESULTS: In vitro lactulose/mannitol flux ratios were close to 0.8 in all species. Urinary recovery ratios differed between rodents and cats or humans; low ratios in cats and humans were due to high mannitol recovery. CONCLUSIONS: Interspecies variation in urinary recovery of mannitol is caused by differences specific for the intact small intestines in vivo. Because hyperosmolality of villus tips in vivo varies, being highest in humans and cats as a result of vascular countercurrent multiplication, it is hypothesized that the high urinary recovery of mannitol in these species is caused by solvent drag through pores that allow the passage of mannitol but not of lactulose. Therefore, the lactulose/mannitol ratio is primarily a standard for the normal functioning of villus epithelial cells in metabolite absorption and for normal villus blood flow. PMID- 7875472 TI - Conscious sedation for gastroscopy: patient tolerance and cardiorespiratory parameters. AB - BACKGROUND/AIMS: Most patients receive conscious sedation for gastroscopy. However, the benefit of the most often used combination of low-dose intravenous midazolam and topical lidocaine on patient tolerance remains poorly defined and has not been shown to outweigh cardiorespiratory risks. To respond to these issues, a randomized, double-blind, placebo-controlled prospective study was performed. METHODS: Two hundred outpatients undergoing diagnostic gastroscopy were assigned to receive either (1) midazolam (35 micrograms/kg) and lidocaine spray (100 mg), (2) midazolam and placebo lidocaine, (3) placebo midazolam and lidocaine, or (4) placebo midazolam and placebo lidocaine. RESULTS: Tolerance (visual analogue scale, 0-100 points; 0, excellent; 100, unbearable) improved as compared with placebo midazolam and placebo lidocaine by 23 points (95% confidence interval, 15-32) in group 1, 15 points (95% confidence interval, 7-24) in group 2, and 10 points (95% confidence interval, 2-18) in group 3. Increasing age (P < 0.001), low anxiety (P < 0.001), and male sex (P < 0.03), but not amnesia, were associated with better patient tolerance. Oxygen desaturation (< 1 minute) occurred in 8.2% and was not more frequent after midazolam treatment. Hypotension was rare (2.1%), and no adverse outcome occurred. CONCLUSIONS: Both low-dose midazolam (35 micrograms/kg) and lidocaine spray have an additive beneficial effect on patients tolerance and rarely induce significant alterations in cardiorespiratory monitoring parameters, thus supporting the widespread use of conscious sedation. PMID- 7875473 TI - Histamine H1 and H3 vasodilator mechanisms in the guinea pig ileum. AB - BACKGROUND/AIMS: Histamine dilates gastrointestinal blood vessels. Whether this is caused by direct activation of vascular histamine receptors or by activation of enteric neurons is not known. The aim of this study was to determine which of these pathways is activated by histamine and to examine the cellular mechanisms involved. METHODS: The effects of histamine were studied in in vitro submucosal preparations from the guinea pig ileum using videomicroscopy to monitor changes in submucosal arteriolar diameter. RESULTS: Histamine caused a tetrodotoxin insensitive dose-dependent dilation (median effective concentration [EC50], 1 mumol/L), showing direct activation of vascular histamine receptors. The H1 antagonist pyrilamine, but not the H2 blocker ranitidine, competitively inhibited the histamine dilatation. The nitric oxide synthase inhibitor NG-monomethyl-L arginine (L-NMMA) inhibited histamine vasodilations by 66%. Indomethacin alone did not alter histamine vasodilations but, when combined with L-NMMA, caused a significantly greater inhibition of the histamine response compared with L-NMMA alone. L-Arginine prevented the actions of L-NMMA. In the presence of both H1 and H2 antagonists, periarteriolar stimulation of sympathetic nerves evoked a tetrodotoxin-sensitive vasoconstriction, which was inhibited by histamine (EC50, 0.8 mumol/L). This histamine action was blocked by the H3 antagonist thioperamide. CONCLUSIONS: Histamine can produce vasodilation of submucosal arterioles by two distinct mechanisms: activation of vascular H1 receptors resulting in release of nitric oxide from endothelium and activation of H3 receptors on sympathetic nerve terminals resulting in presynaptic inhibition of vasoconstrictor tone. PMID- 7875474 TI - Vitamin E enhances the lymphatic transport of beta-carotene and its conversion to vitamin A in the ferret. AB - BACKGROUND/AIMS: beta-Carotene and alpha-tocopherol may have either antagonistic or synergistic effects on each other's absorption and metabolism. The effects of both physiological and pharmacological concentrations of alpha-tocopherol on the absorption and metabolism of beta-carotene in ferret intestine were determined. METHODS: A high concentration of beta-carotene was perfused through the upper portion of the small intestine of ferrets in vivo with varying levels of alpha tocopherol. The effluent of a mesenteric lymph duct cannulation, the intestinal mucosal scraping, and portal vein blood were sampled and analyzed by high performance liquid chromatography. RESULTS: The lymphatic transport of beta carotene was enhanced 4-fold by alpha-tocopherol at a physiological dose and 12 21-fold at a pharmacological dose. The lymphatic transport of alpha-tocopherol was linearly (r = 0.8; P < 0.05) related to the luminal alpha-tocopherol concentration even in the presence of a high concentration of beta-carotene. Furthermore, alpha-tocopherol increased the conversion of beta-carotene into retinol in the intestine in a dose-dependent manner. CONCLUSIONS: alpha Tocopherol has a positive effect on the intestinal absorption of intact beta carotene and may modulate the metabolic conversion of beta-carotene into retinoids. PMID- 7875475 TI - Mediation of hyperglycemia-evoked gastric slow-wave dysrhythmias by endogenous prostaglandins. AB - BACKGROUND/AIMS: Antral hypomotility and gastric dysrhythmias occur in diabetic gastroparesis. This study tested the hypothesis that acute hyperglycemia suppresses fed antral contractions and disrupts slow-wave rhythmicity via prostaglandin pathways. METHODS: Six normal volunteers underwent electrogastrography and antroduodenal manometry under control, hyperglycemic clamp, and euglycemic, hyperinsulinemic clamp conditions before and after administration of indomethacin (50 mg orally three times daily for 3 days). RESULTS: Hyperglycemic clamping to 230 mg/dL evoked a 4-fold increase in tachygastric activity and a 2.6-fold increase in arrhythmic activity (P < 0.05), whereas 140 and 175 mg/dL did not induce dysrhythmias. Antral motility indexes were reduced by 58% +/- 14% at 175 mg/dL and 70% +/- 8% at 230 mg/dL after a 750 kcal meal. Euglycemic, hyperinsulinemic clamping to insulin levels observed with the highest glucose infusions did not produce tachyarrhythmias or hypomotility. After indomethacin, hyperglycemic clamping to 230 mg/dL did not induce tachyarrhythmias. In contrast, indomethacin did not prevent the reduction in motility evoked by hyperglycemic clamping. CONCLUSIONS: Acute hyperglycemia, but not hyperinsulinemia, inhibits fed antral motility and induces gastric dysrhythmias at higher plasma glucose levels. Induction of dysrhythmias, but not hypomotility, is dependent on endogenous prostaglandin synthesis. These findings offer insight into the myoelectric disturbances of diabetic gastroparesis and suggest a possible therapeutic role for prostaglandin synthesis inhibitors for gastric dysrhythmias in this condition. PMID- 7875476 TI - Metabolism of ethanol in rat gastric cells and its inhibition by cimetidine. AB - BACKGROUND/AIMS: Several studies have shown that the stomach has sufficient alcohol dehydrogenase activity to metabolize a significant amount of alcohol and that cimetidine depresses this alcohol dehydrogenase activity. However, both gastric metabolism of ethanol and its inhibition by cimetidine remain controversial. Given the difficulty in assessing gastric metabolism of ethanol in vivo, this subject was investigated in vitro. METHODS: Cultured rat gastric epithelial cells were incubated with 200 mmol/L [1-14C]ethanol for 90 minutes with and without cimetidine (0.1-1 mmol/L) or omeprazole (1 mmol/L). The quantity of ethanol oxidized by gastric cells was measured by the amount of acetate produced using ion exchange chromatography. RESULTS: The majority of cells at confluency had typical features of mucous cells. The gastric cells metabolized significant amounts of ethanol, sufficient to account for in vivo first-pass metabolism of ethanol in rats. Cimetidine, but not omeprazole, reduced ethanol metabolism by 39.9% +/- 4.9% (P < 0.01), an inhibition comparable with that previously reported for first-pass metabolism in vivo. CONCLUSIONS: Gastric cells in tissue culture are capable of significant ethanol oxidation, the in vitro rates are sufficient to account for first-pass metabolism of ethanol in vivo, and cimetidine inhibits ethanol metabolism in tissue culture, an effect that parallels its decrease of first-pass metabolism in vivo. PMID- 7875477 TI - Effect of three laxatives and a cation exchange resin on fecal sodium and potassium excretion. AB - BACKGROUND/AIMS: The treatment of hyperkalemia in patients with renal insufficiency often includes the ingestion of sorbitol and a cation exchange resin. Sorbitol alone may be used to remove sodium and water from overloaded patients. The efficacy of these regimens has never been compared with other laxative or laxative-resin combinations. The aim of the study was to compare the relative effect of three laxatives with different mechanisms of action, alone and in combination with resin, on fecal sodium and potassium excretion. METHODS: Sodium, potassium, and water excretion in 12-hour stool collections were analyzed after various laxative-resin combinations in normal subjects. RESULTS: Correctol (yellow phenolphthalein) (Schering Plough Health Care Products, Memphis, TN) was more effective than sorbitol or sodium sulfate in causing fecal sodium and potassium loss. Resin recovery in stool was much greater with phenolphthalein than with other laxatives, and more potassium was excreted in stool with phenolphthalein-resin than with phenolphthalein alone or other laxative-resin combinations. Sorbitol caused more undesirable gastrointestinal symptoms than did sodium sulfate or phenolphthalein. CONCLUSIONS: In normal people, phenolphthalein (1) is preferable to other laxatives in causing fecal sodium and potassium excretion, (2) hastens resin transit through the intestine compared with other laxatives, and (3) produces greater fecal potassium excretion when combined with resin than phenolphthalein alone or other laxative-resin combinations. PMID- 7875478 TI - Tumor necrosis factor alpha: a major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats. AB - BACKGROUND/AIMS: Portal hypertension is often accompanied by a hyperdynamic circulatory syndrome. Tumor necrosis factor (TNF) alpha causes vasodilatation and a hyperdynamic state in mammals by activating nitric oxide synthesis. The aim of this study was to investigate whether TNF-alpha plays a role in developing the hyperdynamic syndrome in portal hypertension. METHODS: Portal-hypertensive rats, induced by partial ligation of the portal vein (PVL), were used. In experiment 1, rats that underwent PVL were treated with polyclonal anti-mouse TNF-alpha or placebo intravenously the same day of the PVL operation and 24 hours before hemodynamic studies. Hemodynamic studies were performed 5 days after PVL. In experiment 2, rats that underwent PVL received anti-TNF-alpha or placebo intravenously 3 days and 24 hours before hemodynamics as in experiment 1. Hemodynamics were performed 14 days after the PVL operation. TNF-alpha blood levels were measured using a bioassay. RESULTS: Anti-TNF-alpha treatment induced a significant increase in mean arterial pressure, heart rate, and systemic vascular resistance and a significant decrease in cardiac index, portal pressure, and TNF-alpha levels in comparison with placebo animals. No significant effects were observed in sham rats. CONCLUSIONS: Anti-TNF-alpha treatment in rats that underwent PVL significantly blunts the development of the hyperdynamic circulation and reduces portal pressure. TNF-alpha may play a role in the hemodynamic abnormalities of portal hypertension. PMID- 7875479 TI - Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma. AB - BACKGROUND/AIMS: Postoperative intrahepatic recurrence of human hepatocellular carcinoma is high. Recently, the relationship between proliferating cell activity in the cirrhotic liver and occurrence or recurrence of hepatocellular carcinoma has been reported. METHODS: One hundred two resected cases of small hepatocellular carcinoma of < 3 cm in diameter without venous invasion or intrahepatic metastasis were examined to ascertain the factors affecting postoperative intrahepatic recurrence. RESULTS: Cumulative intrahepatic recurrence rates at 1, 3, and 5 years after surgery were 12.0%, 57.2%, and 67.6%, respectively. The log-rank test indicated that serum albumin levels of < 3.7 g/dL, alanine aminotransferase levels of more than 54 IU/L, active inflammation in the nontumorous portion, and high proliferating cell nuclear antigen labeling index in the nontumorous portion (> 23.2%) were significant risk factors for recurrence. Tumor factors, including tumor size, histological grade, or alpha fetoprotein level, were not significant risk factors. Cox's proportional hazard model identified that serum albumin level and alanine aminotransferase level were independently associated with intrahepatic recurrence after hepatectomy. CONCLUSIONS: This study suggests that the principal cause linked to either a recurrence or a second new growth of hepatocellular carcinoma in the remnant liver after hepatectomy was the state of the underlying liver parenchyma as well as other tumor factors per se. PMID- 7875480 TI - In vivo hepatic 31P magnetic resonance spectroscopy in chronic alcohol abusers. AB - BACKGROUND/AIMS: In vivo hepatic 31P magnetic resonance spectroscopy (MRS) can provide information on hepatic energy metabolism, phospholipid substrates, and hepatocyte lipid bilayers. The aim of this study was to ascertain the effects of alcohol ingestion on hepatic 31P spectral variables. METHODS: Twenty-six chronic alcohol abusers underwent hepatic 31P MRS 6-12 hours after their last alcoholic drink; studies were repeated in 17 individuals following abstinence from alcohol. The reference population comprised 16 healthy volunteers. Ratios of phosphomonoesters (PME), inorganic phosphate, and phosphodiesters (PDE) relative to beta-adenosine triphosphate (ATP) were measured. RESULTS: In patients with minimal liver injury, recent drinking was associated with a significant elevation in the mean PDE/ATP ratio (P < 0.0001) and an increase in mean PME/ATP, which was not significant; abstinence was associated with reductions in both metabolite ratios. In patients with alcoholic cirrhosis, recent drinking was associated with an elevation in mean PME/ATP (P < 0.05) and an increase in mean PDE/ATP, which was not significant; abstinence was associated with no significant change in PME/ATP but with a reduction in PDE/ATP. CONCLUSIONS: In the absence of significant liver injury, chronic alcohol abuse is associated with the elevation of PME/ATP, possibly reflecting changes in hepatic redox potential, and of PDE/ATP, most likely reflecting the induction of hepatocyte endoplasmic reticulum. In the presence of cirrhosis, these changes are attenuated and modified. PMID- 7875481 TI - Natural history of hepatitis D viral superinfection: significance of viremia detected by polymerase chain reaction. AB - BACKGROUND/AIMS: Polymerase chain reaction (PCR) is very sensitive. The aim of the study was to reevaluate viral replication in hepatitis D virus (HDV) superinfection by PCR. METHODS: HDV and hepatitis B virus (HBV) were detected by PCR in 185 patients. RESULTS: The acute hepatitis group had the highest detection rate of HDV RNA compared with chronic hepatitis, cirrhosis, hepatocellular carcinoma, and remission groups (63 of 64 vs. 35 of 47, 17 of 23, 19 of 30, and 7 of 21) and the highest alanine aminotransferase (ALT) levels (mean, 1741 U/L vs. 266 to 27 U/L; P < 0.05). The detection rate of HBV DNA was the lowest in the acute group (41%) compared with 66%, 70%, 80%, and 57% in the remaining groups (P < 0.02). At the chronic stage, 13%-25% of cases had HDV RNA, and 30%-48% of cases had HBV DNA detected by PCR but not by traditional method. HDV RNA was associated with ALT levels in horizontal and longitudinal analyses. CONCLUSIONS: HDV superinfection may be divided into the following three phases: acute phase, active HDV replication and suppression of HBV with high ALT levels; chronic phase, decreasing HDV and reactivating HBV with moderate ALT levels; and late phase, development of cirrhosis and hepatocellular carcinoma caused by replication of either virus or remission resulting from marked reduction of both viruses. PMID- 7875482 TI - Prolonged antagonism of alpha 1-adrenergic vasoconstriction in the rat liver by atrial natriuretic peptide. AB - BACKGROUND/AIMS: Vasodilator hormones that regulate hepatic circulation at physiological concentrations have not been sufficiently identified. The presence of atrial natriuretic peptide (ANP) and its receptors in the hepatic vascular bed suggest such vasorelaxing potential. METHODS: Livers of male Sprague-Dawley rats were perfused in a flow-constant fashion. The selective alpha 1-adrenergic agonist phenylephrine (PE) (1.5 mumol/L) was infused from 30 to 36 minutes and again from 70 to 76 minutes after starting perfusion (n = 5). ANP (0.1 pmol/L to 200 nmol/L), des-(Gln18, Ser19, Gly20, Leu21, Gly22)-ANP fragment (C-ANP) (20 nmol/L), or 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) (50 mumol/L) (each n = 4) were added from 20 to 40 minutes. RESULTS: During the first infusion of PE, portal pressure increased from 3.7 +/- 0.5 to 12.1 +/- 0.8 cm H2O maximally (mean +/- SD) and increased again to 11.5 +/- 2.0 during the second PE infusion. ANP at physiological concentrations reduced both PE-induced increases of portal pressure in a dose-dependent fashion, reaching half-maximal effects around 20 pmol/L and maximal effects (about 50% inhibition of PE-induced vasoconstriction) at 40 pmol/L. The cGMP analogue 8-Br-cGMP showed the same long lasting vasodilating effect as ANP. In contrast, C-ANP, which binds only to the ANP C-receptor, had no effects. CONCLUSIONS: Physiological concentrations of ANP antagonize alpha 1-adrenergic vasoconstriction in the liver, suggesting an important function in the humoral regulation of hepatic circulation. The prolonged hemodynamic effect of ANP seems to be ANP A-receptor/guanylyl cyclase/cGMP-mediated. PMID- 7875483 TI - Liver cell dysplasia is a major risk factor for hepatocellular carcinoma in cirrhosis: a prospective study. AB - BACKGROUND/AIMS: In humans, the role of liver cell dysplasia as a preneoplastic lesion is still debated. A prospective, long-term, multicenter study was performed to establish whether liver cell dysplasia in cirrhosis is associated with an increased risk for hepatocellular carcinoma (HCC). METHODS: A cohort of 307 consecutive patients in whom liver cirrhosis was diagnosed by histology was investigated for development of HCC at 6-month intervals by ultrasonography and determination of alpha-fetoprotein levels. RESULTS: At enrollment, liver cell dysplasia was found in 75 patients (24%) and in 53% (P < 0.01) of those positive for hepatitis B surface antigen (HBsAg). After a mean follow-up of 46 months, HCC was detected in 45 cases, and it was significantly more frequent in patients with liver cell dysplasia (P < 0.01) and HBsAg-serum positivity (P < 0.01). Multivariate analysis showed that liver cell dysplasia was the most important risk factor correlated with HCC development. HBsAg positivity and age over 60 years were also independent risk factors for HCC. CONCLUSIONS: These results indicate that liver cell dysplasia is a major risk factor for HCC, and it should be looked for carefully by pathologists in liver biopsy specimens to identify patients requiring more intensive observation. PMID- 7875484 TI - The relationship between plasma and brain quinolinic acid levels and the severity of hepatic encephalopathy. AB - BACKGROUND/AIMS: Quinolinic acid is an endogenous neuroexcitant derived from tryptophan. Brain quinolinic acid concentrations are reportedly elevated in chronic liver failure. The aim of this study was to determine if brain quinolinic acid levels correlate with the severity of hepatic encephalopathy. METHODS: Postmortem samples of selected brain regions and plasma samples taken at several stages of encephalopathy were obtained from patients with acute and chronic liver failure. Quinolinic acid levels were measured by mass spectroscopy using [18O]quinolinic acid. RESULTS: Plasma quinolinic acid levels were significantly increased by stage I encephalopathy in patients with acute liver failure and by stages II and III in patients with chronic liver failure. Brain quinolinic acid levels were elevated only in patients with acute liver failure and were uniformly distributed at concentrations below those observed in plasma. CONCLUSIONS: The uniform distribution of quinolinic acid at subplasma concentrations in the brains of patients with acute liver failure suggests that it is synthesized peripherally and enters the brain across a permeabilized blood-brain barrier. Whereas the elevation of brain quinolinic acid levels in patients who died of acute but not chronic liver failure suggests that the involvement of quinolinic acid in the pathogenesis of hepatic encephalopathy is minimal, it could predispose these patients to seizures. PMID- 7875485 TI - Isolation of the microtubule-vesicle motor kinesin from rat liver: selective inhibition by cholestatic bile acids. AB - BACKGROUND/AIMS: Vesicular transport is supported by microtubule-based, force transducing adenosine triphosphatases (ATPases), such as kinesin, a ubiquitous motor enzyme that has been well studied in neuronal tissues. Although vesicular transport is important for hepatocellular secretory and clearance activities, the role of kinesin in liver function is poorly understood. Furthermore, the effects of bile acids on kinesin are unknown. METHODS: Kinesin was purified from rat liver cytosol by conventional chromatography and microtubule affinity binding and was characterized by immunoblotting with domain-specific kinesin antibodies and amino acid sequencing of tryptic fragments. Kinesin activity was measured with and without bile acids using an in vitro motility assay and ATPase assays. RESULTS: Immunoblot analysis and partial amino acid sequencing of purified kinesin showed that the sequence at the heavy chain of hepatic kinesin is nearly identical to that of brain kinesin. Purified kinesin transported microtubules in vitro with a velocity of approximately 0.5 microns/s; this activity was significantly inhibited by 0.5-1 mmol/L taurochenodeoxycholate but not by tauroursodeoxycholate. At a dose of 1 mmol/L, chenodeoxycholate conjugates, but not ursodeoxycholate or cholate conjugates, directly inhibited the ATPase activities of kinesin and another microtubule motor, cytoplasmic dynein. CONCLUSIONS: Cholestatic concentrations of chenodeoxycholate conjugates directly inhibit the activity of microtubule motors, suggesting a possible mechanism for impairment of vesicular transport in cholestasis. PMID- 7875486 TI - Derangements in the activin-follistatin system in hepatoma cells. AB - BACKGROUND/AIMS: The growth of normal hepatocytes is regulated by the activin follistatin system. The aim of this study was to investigate the activin follistatin system in hepatoma cells. METHODS: The production and action of activin and follistatin in human hepatoma cell lines were examined. Activin A and follistatin were measured by bioassay and protein-binding assay, respectively. RESULTS: Activin A inhibited cell growth in HepG2 cells but not in either PLC/PRF/5 or HLE cells. However, the effect of activin A in HepG2 cells was attenuated at high cell density. In HepG2 cells, two classes of activin-binding sites were expressed, and affinity cross-linking showed that 125I-activin A bound specifically to three proteins with molecular weights of 48, 67, and 94 kilodaltons. In PLC/PRF/5 cells, a single class of binding site was observed, and the binding capacity was approximately 60% of the capacity in HepG2 cells. Virtually no 125I-activin A binding was detected in HLE cells. Bioactivity and messenger RNA for activin A were undetectable in three cell lines. In contrast, follistatin was released from three cell lines. CONCLUSIONS: Multiple alterations in the activin-follistatin system were found in three hepatoma cell lines. The accelerated growth observed in hepatoma cells may be caused, at least partly, by the attenuation of the action of activin A. PMID- 7875487 TI - Nitric oxide blocks bile canalicular contraction by inhibiting inositol trisphosphate-dependent calcium mobilization. AB - BACKGROUND/AIMS: The biochemical mechanism of bile canalicular contraction is similar to that of smooth muscle contraction. Contraction follows inositol-1,4,5 trisphosphate (InsP3)-dependent Ca2+ release, which activates actin-myosin interactions. Nitric oxide is a myorelaxant through the actions of 5'-cyclic guanosine monophosphate (cGMP) and is produced in hepatocytes exposed to endotoxin and cytokines. The aim of this study was to investigate the effect of nitric oxide on canalicular contraction and to determine the mechanism by which cGMP interferes with the contractile signal. METHODS: The canalicular motility in rat hepatocyte doublets was measured by microscopic image analysis, and intracellular Ca2+ was measured by fluorescence microscopy. cGMP and InsP3 were determined by radio-immunoassay and high-pressure liquid chromatography. Ca2+ release from liver homogenate was measured by filtration and superfusion assays. RESULTS: Compounds that release nitric oxide stimulated hepatocellular production of cGMP and prevented agonist-induced contraction by inhibiting the increase in intracellular Ca2+. The cGMP analogue bromo-cGMP prevented contraction and the increase in Ca2+. Bromo-cGMP marginally decreased InsP3 production. cGMP blocked InsP3-dependent Ca2+ release from internal stores. CONCLUSIONS: These findings suggest that nitric oxide interferes with Ca2+ signals by cGMP-mediated inhibition of the InsP3 receptor/Ca2+ channel and that hepatocellular production of nitric oxide may be cholestatic by impairing canalicular motility. PMID- 7875488 TI - Secretin causes H+/HCO3- secretion from pig pancreatic ductules by vacuolar-type H(+)-adenosine triphosphatase. AB - BACKGROUND/AIMS: Secretin stimulates pancreatic ductules to secrete HCO3- into pancreatic juice and H+ into interstitial fluid. The aim of the present study was first to examine whether ductular H+ secretion is inhibited by micromolar concentrations of bafilomycin A1, which blocks vacuolar H(+)-adenosine triphosphatase by specific action, and secondly to test for evidence of ductular Na+/HCO3- cotransport. METHODS: Ductular H+ secretion was estimated from the rate of intracellular pH recovery after acid-loading (24 mmol/L NH4Cl) microdissected pancreatic ductules from pig, mounted in a flow-through perfusion chamber on the stage of a fluorescent microscope. Intracellular pH was measured using the fluorescent pH indicator 2'7'-bis (carboxyethyl)-5,6-carboxyfluorescein and dual wave-length excitation of fluorescence. The ducts were superfused perfused with either HCO3(-)-free HEPES-containing buffers or HCO3(-)-containing buffers. RESULTS: Secretin (10(-8) mol/L) induced a net H+ secretion of 1.87 +/- 0.23 mumol.mL cell vol-1.min-1 that was blocked by 10(-6) mol/L bafilomycin A1 and was unaffected by Na+ substitution with choline using HEPES superfusion buffers. Secretin-stimulated ductules superfused with bicarbonate-containing, Cl(-)-free buffers showed Na(+)-dependent and 4,4'-diisothiocyanostilbene-2, 2'-disulfonic acid-inhibitable alkalinization of intracellular pH. CONCLUSIONS: Secretin causes H+/HCO3- secretion from pancreatic ductules by a mechanism involving vacuolar type H(+)-adenosine phosphatase. Pancreatic ductules also show Na+/HCO3- cotransport, which may account for a small fraction of secreted bicarbonate. PMID- 7875489 TI - Molecular genetic evidence of bacterial colonization of cholesterol gallstones. AB - BACKGROUND/AIMS: Cholesterol gallstone formation is believed to be unrelated to the presence of bacteria because attempts to culture potentially causative bacteria from surgically removed cholesterol stones have failed. However, the formation of gallbladder gallstones takes years. Embedded bacteria may be damaged or killed. The aim of this study was to search for bacterial DNA sequences in cholesterol stones with negative bacterial culture. METHODS: Bacterial gene fragments were amplified in vitro from DNA extracted from cholesterol gallbladder stones. Comparative 16S ribosomal RNA sequence analysis was used for identification. RESULTS: Gallstones with cholesterol content between 70% to 90% harbored bacterial DNA (16 of 17 patients). No bacterial DNA was found in the gallstones with cholesterol content of > 90% (3 patients). Three bacterial groups typical for gallstone colonization were identified. Propionibacteria-related DNA was found in the stones of 9 patients (45%). Enterobacterial type sequences were obtained in 5 patients (25%). A more heterogenous sequence collection was retrieved from 7 patients (35%) and could be assigned to the major bacterial line of gram-positive bacteria with a low DNA guanine and cytosine content. CONCLUSIONS: Most cholesterol gallstones harbor bacterial DNA. It is important to determine the actual role of these microorganisms in gallstone formation. PMID- 7875490 TI - Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. AB - BACKGROUND/AIMS: The diagnosis of cholangiocarcinoma in primary sclerosing cholangitis (PSC), even with the use of current imaging techniques and brush cytology, is difficult and particularly important in patients being assessed for liver transplantation. This study investigated the accuracy of serum levels of a combination of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in the diagnosis of cholangiocarcinoma in patients with PSC. METHODS: Seventy-four patients with PSC were studied. Fifteen patients had tumors (11 occult on imaging), 22 had severe PSC that necessitated transplantation (with explanted liver known to be free of tumor), and 37 patients had stable PSC. RESULTS: An index of the two serum tumor markers [using the formula CA19-9 + (CEA x 40)] gave an accuracy of 86% in diagnosis of cholangiocarcinoma, with 10 of the 15 cases of cholangiocarcinoma having an increased value compared with none in a group of 22 comparable cases with no tumor. In addition, 6 of the 11 patients with occult tumors had abnormal values. Ultrasonography, computerized tomographic scanning, and endoscopic retrograde cholangiopancreatography were poor predictors of the presence of tumor. CONCLUSIONS: A combination of serum tumor markers will identify most occult tumors and will improve selection of appropriate cases for orthotopic liver transplantation. PMID- 7875491 TI - HLA-DR and HLA-DQ are not markers for rapid disease progression in primary sclerosing cholangitis. AB - BACKGROUND/AIMS: The association between primary sclerosing cholangitis (PSC) and the HLA haplotype A1, B8, DR3, DQ2 is well established. During the last few years, several additional HLA associations have been suggested in PSC. Furthermore, two different HLA-DR specificities have been reported to be markers for rapid disease progression. Our aim was to critically evaluate all of the current and as yet mostly unconfirmed HLA class II issues in PSC. METHODS: Seventy-five Swedish patients with PSC were HLA-DR and HLA-DQ genotyped. RESULTS: Of the recently described HLA associations in PSC, the association with the DRB1*1301, DQA1*0103, DQB1*0603 haplotype was decisively confirmed, whereas the DRB1*04 specificity was only slightly under-represented and the frequency of DR2 was neutral. The association with codon 38 of DRB genes was secondary to the DRB3*0101 association. HLA-DR and HLA-DQ alleles were not found to be markers of disease progression. CONCLUSIONS: The HLA-associated genetic susceptibility to PSC cannot be attributed to specific amino acid positions of the DR beta chains. The highly discrepant results obtained in two previously reported studies and the present investigation indicate that HLA class II alleles are not markers for a more aggressive clinical course in PSC. PMID- 7875492 TI - Orthotopic liver transplantation for chronic hepatitis in two patients with common variable immunodeficiency. AB - Two patients with common variable immunodeficiency underwent orthotopic liver transplantation for chronic hepatitis, unequivocally caused by hepatitis C virus in one case. Although one patient had pneumonia 8 days after surgery and the other developed hepatic venular stenosis in the transplanted liver, both had a reasonably good quality of life for at least 15 months. However, both subsequently died of recurrent hepatitis C virus hepatitis or hemorrhage after splenectomy for hypersplenism. This shows that severe infection is not a major problem in patients with common variable immunodeficiency after liver transplantation provided they undergo prophylactic antimicrobial and immunoglobulin therapy. The longer term prognosis must be regarded as poor until more data are available following transplantation in similar patients. PMID- 7875493 TI - Copper-induced acute rhabdomyolysis in Wilson's disease. AB - Wilson's disease is a lethal defect in copper metabolism causing a continual increase in tissue copper concentrations that become toxic to the liver, brain, kidney, eye, skeletal system, and several other tissues and organs. The liver is unique among these in being both the site of the etiologic biochemical abnormality and the organ that is always affected by copper toxicosis. Although myocardial muscle involvement has been reported in association with Wilson's disease, copper deposits in peripheral muscle tissue have not yet been described. A case of a young patient with Wilson's disease who developed recurrent episodes of acute rhabdomyolysis is presented, and the accumulation of copper in muscle tissue as a possible complication is discussed. PMID- 7875494 TI - Amino acid transport by small intestinal, hepatic, and pancreatic epithelia. PMID- 7875495 TI - Crohn's disease: pathogenesis and persistent measles virus infection. AB - The Inflammatory Bowel Disease Study Group at the Royal Free Hospital School of Medicine has tested the hypothesis that the primary pathological abnormality in Crohn's disease is in the mesenteric blood supply. Early morphological studies involved arterial perfusion-fixation and either resin casting and scanning electron microscopy or vascular immunostaining of resected intestine affected by Crohn's disease. Granulomatous and lymphocytic damage to intramural blood vessels, even in macroscopically normal areas, was observed. We put forward possible mechanisms by which a chronic ischemic process might account for many of the idiosyncracies of Crohn's disease. It was proposed that persistent viral infection of the mesenteric microvascular endothelium might underly this vasculitic process; based on certain behavioral characteristics of measles virus, including its tropism for the submucosal endothelium of the intestine, this agent was investigated further. This report reviews the preliminary evidence from both epidemiological and basic scientific data for persistent measles virus in the intestine of patients with Crohn's disease. Possible mechanisms for virus persistence and subsequent reactivation are discussed. In conclusion, we believe that Crohn's disease may be a chronic granulomatous vasculitis in reaction to a persistent infection with measles virus within the vascular endothelium. This granulomatous inflammation, perhaps aggravated by either a hypercoagulable state or mechanical stress, results in the clinical features of Crohn's disease. PMID- 7875496 TI - Gastroscopy is incomplete without biopsy: clinical relevance of distinguishing gastropathy from gastritis. PMID- 7875497 TI - American Gastroenterological Association policy statement on the use of medical practice guidelines by managed care organizations and insurance carriers. PMID- 7875498 TI - Gut feelings: what turns them on? PMID- 7875499 TI - Sedation and analgesia for endoscopy. PMID- 7875500 TI - Bacteria and cholesterol gallstones: molecular biology comes to gallstone pathogenesis. PMID- 7875502 TI - Accuracy of endoscopic measurements: sizing up the problem. PMID- 7875501 TI - Does HLA status influence prognosis in primary sclerosing cholangitis? PMID- 7875503 TI - Cyclosporine and inflammatory bowel disease: still more questions. PMID- 7875504 TI - Mapping a strategy for curing hepatitis C. PMID- 7875505 TI - Duplicate publication: additional comments. PMID- 7875506 TI - Acute antroduodenal dysautonomia with hyperglycemia. PMID- 7875507 TI - Interventional radiology at the crossroads. PMID- 7875508 TI - Tempest about T-lymphocyte apheresis in Crohn's disease. PMID- 7875509 TI - Prospective studies of the mucosa of the ileoanal pouch. PMID- 7875510 TI - Use of TIPS for refractory, not routine, variceal hemorrhage. PMID- 7875511 TI - [Clinico-morphologic comparison of pulmonary lesions in acute leukemia]. AB - The authors provide x-ray and postmortem examination data on pulmonary lesions in 36 patients with acute leukemia. Morphological lesions revealed in 80% of the examinees were as follows: hemorrhage, leukemic pneumonitis, secondary pneumonia (64%, 25% and 17% of case, respectively). The risk factors comprise severe and long-term thrombocytopenia, leukocytosis, long-term post-cytostatic agranulocytosis. It is stated that frequent pulmonary involvement in acute leukemia and the absence of specific clinicoroentgenological picture of pneumopathy often result in misdiagnosis. Wider use of fibrobronchoscopy with bronchoalveolar lavage examination and transbronchial pulmonary biopsy is recommended to advance the diagnosis and treatment of pulmonary lesions in acute leukemia. PMID- 7875512 TI - [Activity of nucleolar organizers in megakaryocytes from patients with leukemia]. AB - The activity of nucleolar organizer regions (NOR) in megakaryocytes (MK) from 21 patients with acute lymphoblastic leukemia (ALL), 35 patients with acute nonlymphoblastic leukemia (ANLL) and 12 patients with blast crisis of chronic myeloid leukemia (BC CML) were studied by silver staining. The control group consisted of 12 donors. The activity of NOR in the whole population of MK and in groups of MK with 1-3, 4-6, 7 and over lobules per nucleus (MK 1, 2 and 3 class, respectively) were taken into account. The activity of NOR in the group of first class MK from patients with acute leukemia (ALL and ANLL) was detected low. On the contrary, it was high in the group of third-class MK of those patients, as compared to the control. The activity of NOR in MK of BC CML patients was significantly lower as compared both to the control and to patients with acute leukemia. The cause of changing the functional state of MK in varying hematology disease has been discussed. PMID- 7875514 TI - [Pathogenetic mechanisms of the so-called astronauts' anemia]. AB - The authors analyze the literature data published in the last 20 years on clinical, laboratory, physiological, hematological and biochemical evidence obtained at preflight and postflight examinations of astronauts and experimental animals who spent 5-12 months in space. After space flights the astronauts exhibited a noticeable decrease in red cell mass, in reticulocyte count, hemoglobin and erythropoietin levels (associated with hypochromia and hyposideremia). This condition of erythron in microgravity is termed astronauts' anemia. The authors consider such anemia as an adaptive erythrocytopenic microgravity syndrome with complicated pathogenesis and suggest its model in the form of acquired transitory thalassemia. PMID- 7875513 TI - [Morphometric analysis of lymphocyte nuclei in chronic lymphocytic leukemia]. AB - This work is dedicated to the study of use of quantitative analysis of cell nucleus structure for the analysis of peripheral blood lymphocytes in patients with chronic lymphocytic leukaemia. The structure of lymphocytic nuclei of healthy donors was evaluated by means of staining by toluidine blue purified cell suspensions smears. The preparations were analysed on the television measuring system "omnicon" with measurements of the following parameters: square of the nucleus, euchromatin, heterochromatin, and the ratio of heterochromatin and euchromatin squares. Actuarial analysis and nuclei classification of the previously mentioned parameters showed, that in peripheral blood of patients with chronic lymphocytic leukemia a large amount of atypical lymphocytes is present with reduced nucleus sizes. Atypical cells retain the ratio of structural components of chromatine, characteristic to normal cells, which show their low proliferative activity. PMID- 7875515 TI - [Prevention of new cases of the disease in families of hemophilia patients in Moscow using a genetic register]. AB - The genetic familial register in question contains information on 441 hemophilia patients. Two-thirds of the patients suffered from moderate or severe hemophilia, 81.3% had hemophilia A. Fifty-two families with the latter disease were examined with molecular methods which confirmed heterozygous carriage in 40% of the female examinees. The prenatal diagnosis in two families led to delivery of healthy boys. The genetic register provides effective protection for hemophiliac families. PMID- 7875516 TI - [Leukemia, lymphogranulomatosis and histiocytosis of Langerhans in children with a history of enlarged thymus gland]. AB - The group consisted of 1056 children with enlarged thymus and a monitored catamnesis in 317 of 0.5-23 years. In 5 examinations in different periods after the diagnosis of enlarged thymus, haematological malignancies were diagnosed: acute lymphoblastic leukaemia (2 children), lymphogranulomatosis (1 child), chronic myeloid leukaemia (monocytic variant) and histiocytosis of Langerhans (1 child). The comparison of these data with other publications on the prevalence of these diseases in the population and the rate of mortality in Moscow place the children with enlarged thymus to high-risk group for haematological malignancies. PMID- 7875518 TI - [Change in functional and metabolic activity of leukocytes and content of serum immunoglobulins of donor blood exposed to gamma radiation]. AB - Changes in functional-metabolic activity of leukocytes and in donor serum immunoglobulin level in exposure to gamma radiation. B.S. Nagoev. Kabardin-Balkar University, Nalchik. The study of 40 samples of blood after 1-4 days of storage revealed a moderate significant reduction in concentrations of cation protein, in myeloperoxidase activity. In exposure to gamma radiation, there appeared dose- and intensity-related shifts in the blood elements morphology, inhibition of myeloperoxidase, in the content of leukocyte cation protein, serum immunoglobulins. These alterations in white blood morphological picture, inhibition of functional-metabolic activity of leukocytes and immunoglobulin unbalance during gamma radiation of isolated blood explain depression of immunobiological characteristics of the body in extreme conditions, particularly, the lack of antibacterial defense as a result of ionizing radiation. PMID- 7875517 TI - [Effect of media conditioned with bone marrow fibroblasts on proliferation of leukemic blast cell lines]. AB - The influence of condition media of bone marrow fibroblasts (BMF) from patients with acute and chronic leukemia (myeloid and lymphoid forms) on the proliferation of K-562, HL-60 and HL-60 leukemic cells treated with tetraphorbol ester inducing macrophage-like differentiation of these cells has been studied. It is shown that BMF inhibit proliferation of leukemic cells, the effect being both direct and mediated by autocrine secretion. BMF effect depends both on the disease specificity and the type of cell line tested. The inhibition effect of BMF on HL 60 also depends on the quantity of megakaryocytes in the primary bone marrow. The role of cell-cell interaction in the ability of bone marrow to influence leukemic blast cells is discussed. PMID- 7875519 TI - [Monoclonal anti-D immunoglobulin for prevention of hemolytic disease of the newborn]. AB - Stable human-mouse heterohybridoma producing human monoclonal anti-D IgG1 has been derived by fusing Epstein-Barr virus (EBV) transformed human immune lymphocytes with mouse myeloma. The absence of EBV DNA in heterohybridoma was demonstrated by the polymerase chain reaction. The antibody was purified by affinity chromatography on protein A Sepharose and tested for sterility, pyrogenicity and toxicity according to the Pharmacopoeia XI and the ability to clear from circulation RhoD-positive red cells. The time of clearance of sensitized RBC was about 3 hrs. Since it is believed to be an association between the rate of RBC clearance by anti-D and the ability of the antibody to suppress the immunization, the monoclonal immunoglobulin may prove suitable for immunoprophylaxis of RhD hemolytic disease. PMID- 7875520 TI - [Epidemiologic registry of leukemia and other hemoblastoses in Briansk region as an instrument of investigation of consequences of the accident at the Chernobyl nuclear power plant]. AB - Beginning from 1986, at Hematological Research Centre (HRC) epidemiological monitoring has been performed on hemoblastoses in Bryansky district, which suffered from the Chernobyl accident more than any other area of Russia. The collection of personal information is organized about each case of disease from all possible sources, diagnosis verification, computer control, storage and analysis of materials. A specialized Register of Blood diseases is created, including demographical and ecological files. Retrospective period of monitoring 1979-1985, afteraccident period-from 1986. In the register 2832 cases were accumulated of hemoblastoses up to 1993. Regions are selected for monitoring with high levels of contamination by 137Cs (15 Ci/sq.km and more), and area for comparison--the other 21 regions of the district. The comparison did not reveal substantial differences. Further epidemiological analysis must be performed. Taking into account dose loads, special studies are initiated. PMID- 7875521 TI - [Role of hematopoietic growth factors and lymphokines in the pathogenesis and treatment of leukemia]. PMID- 7875522 TI - [Gene therapy. Potential for its use]. PMID- 7875523 TI - [Specific immunoglobulin against hepatitis B, producible under conditions of a blood transfusion station]. PMID- 7875524 TI - [Therapeutic plasmapheresis in acute purulent pyelonephritis of pregnancy]. PMID- 7875525 TI - [Immunologic prognostication of development of recurrences in patients with acute myeloid leukemia]. AB - Morphological study of the bone marrow and blood, cytochemical examination with evaluation of lysosomal enzymes activity, concentrations of glycogen and acid sulfated mucopolysaccharides, and immunophenotyping were conducted to develop immunomorphological criteria early detecting leukemic clone in patients with acute nonlymphoblastic leukemia (ANLL) in remission based on dynamic immunological monitoring of peripheral blood lymphocytes for recurrence prognostication. Immunological monitoring of lymphoid population of ANLL patients' peripheral blood allowed to predict recurrence in remission, several months before its morphological identification in all the patients. This was accomplished by a significant increase in the levels of (M + 3 sigma) lymphocytes with antigens of early differentiation stages atypical for mature lymphocytes. Practical value of the method is not only in providing immunophenotypical appearance of the blast cells in various ANLL variants, but also in the control by the detected antigens over the residual leukemic population during treatment, and in prediction of the disease recurrence by reversion in the spectrum of differential antigens on the lymphocytes in remission. The latter indicates the increase of the leukemic clone and may be recognized several months before evident clinicomorphological signs of the aggravation. PMID- 7875526 TI - Propentofylline: a nucleoside transport inhibitor with neuroprotective effects in cerebral ischemia. AB - 1. Adenosine is an endogenous neuroprotective agent; stimulation of A1 receptors decreases excitatory amino acid neurotransmission and stimulation of A2 receptors inhibits platelet and neutrophil activation and promotes vasodilation. 2. Post ischemic administration of propentofylline (HWA 285) reduces neuronal damage in gerbils and improves glucose metabolism in all regions of brain in acute stroke patients. 3. Propentofylline inhibits the transport of adenosine into cultured cells and increases extracellular adenosine concentrations in ischemic brain. Thus, enhanced stimulation of adenosine receptors may account for some of the neuroprotective effects of this compound. 4. Propentofylline inhibits free radical production by cultivated microglia cells, stimulates nerve growth factor production and inhibits cAMP-phosphodiesterase activity. These effects may also be important for neuroprotection. PMID- 7875527 TI - The control of endothelin-1 secretion. AB - 1. The human endothelin-1 (ET-1) gene, which is located on chromosome 6, contains cis-regulatory elements in the 5'-flanking region including the TPA-responsive element, nuclear factor 1 binding element and GATA motif. 2. The expression of preproendothelin-1 (PPET-1) mRNA is regulated by a mechanism involving receptor mediated mobilization of intracellular Ca2+ and activation of protein kinase C in endothelial cells. 3. Activation of protein kinase C results in the synthesis of c-Jun protein and the rapid dephosphorylation of c-Jun protein. Consequently, the binding activity of c-Jun protein to the TPA-responsive element increases, and this causes the induction of PPET-1 mRNA. 4. The microtubular system seems to play some important roles in ET-1 secretion, especially in the process of transferring the synthesized ET-1 to the cell surface of the endothelial cells. 5. The secretion of ET-1 from endothelial cells is also regulated by intracellular Ca2+ released from the Ca2+ store and by Ca2+-calmodulin complex. The phosphorylation of the myosin light chain, elicited by myosin light chain kinase and activated by Ca2+-calmodulin complex, facilitates the formation of filamentous myosin and actin which probably participate in ET-1 secretion especially in transporting the ET-1-containing vesicles towards the cell membrane in the stimulated endothelial cells. 6. Many cultured cells, other than endothelial cells, also secret ET-1 into the culture medium and this secretion can be stimulated by a variety of agents. PMID- 7875528 TI - Ginsenosides evoke endothelium-dependent vascular relaxation in rat aorta. AB - 1. Ginsenoside (10-100 mg/kg, i.v.) lowered blood pressure in a dose-dependent manner in rats. 2. Ginsenoside (10(-5)-3 x 10(-4) g/ml) relaxed the aorta after contractions were induced by 10(-6) M phenylephrine in the aorta with endothelium but not in that without endothelium. 3. The relaxation induced by ginsenoside was attenuated by 3 x 10(-7) M methylene blue (MB) and 10(-4) M NG-monomethyl-L arginine (L-NMMA) but not inhibited by 10(-5) M indomethacin. 4. Ginsenoside (10( 4) g/ml for 2 min) increased the accumulation of cGMP in rings with endothelium. L-NMMA and MB inhibited the accumulation of cGMP induced by ginsenoside. 5. These data suggest that vascular relaxations induced by ginsenoside are mediated by release of endothelium-drived nitric oxide which enhances the accumulation of cGMP. PMID- 7875529 TI - 5-HT receptors on identified Lymnaea neurones in culture: pharmacological characterization of 5-HT2 receptors. AB - 1. Pressure ejection techniques were used to investigate the identify of receptors mediating 5-HT (5-Hydroxytryptamine) effects on the serotonin containing cerebral giant cells (CGCs) of the cerebral ganglia and some of their follower motorneurones from the buccal ganglia of Lymnaea stagnalis in culture. 2. The vertebrate 5-HT2 receptor agonist alpha-methylserotonin maleate (10(-4) M), inhibited most of the neurones inhibited by 5-HT (10(-3) M). Others were excited by both agonists. In cells where 5-HT failed to evoke any effects, the 5 HT2 agonist also lacked an effect. 3. Bath application of the 5-HT2 receptor antagonists ketanserin and methysergide (10(-4) M), not only blocked spike generation, but also reduced both the excitatory and inhibitory responses to both 5-HT and alpha-methylserotonin maleate, while the 5-HT3 antagonist MDL 72222 (10( 4) M) failed to block alpha-methylserotonin maleate effects. 4. At 10(-3) M, alpha-methylserotonin maleate increased the amplitudes of the hyperpolarizing responses in a dose-dependent manner. These responses were blocked by ketanserin (10(-4) M). 5. The above results suggest that 5-HT2 receptors are involved in the responses of the CGCs and the buccal motorneurones to 5-HT in Lymnaea stagnalis. The pharmacological characterization of these receptors indicates that the compounds that interact with the 5-HT2 receptors in mammals also interact with the 5-HT2 receptors in molluscs. PMID- 7875530 TI - Effects of forskolin and organic nitrate on aggregation and intracellular cyclic nucleotide content in human platelets. AB - 1. The present study investigated the effect of a combination between forskolin, a naturally occurring diterpene which directly activates adenylyl cyclase, and glyceryl trinitrate (GTN), which enhances intraplatelet cyclic guanosine monophosphate levels, on human platelet aggregation and intracellular content of cyclic nucleotides 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP). 2. Forskolin inhibited, in a dose-dependent way, platelet aggregation in response to collagen and adrenaline in platelet-rich plasma. In whole blood samples, forskolin inhibited collagen-stimulated aggregation. In presence of forskolin the intraplatelet cAMP levels were significantly increased. 3. GTN directly decreased the platelet response to collagen in whole blood samples (IC50 = 122 mumol/l) and it increased the intraplatelet levels of both cGMP and cAMP. 4. GTN at 20 and 40 mumol potentiated the inhibitory effects of forskolin on platelet aggregation in both platelet-rich plasma and whole blood. 5. Our results suggest a synergistic effect of the simultaneous increase of both cAMP and cGMP on the biochemical steps involved in the inhibition of the platelet response. PMID- 7875531 TI - Biphasic response of the rabbit detrusor muscle to changing the extracellular concentrations of potassium and calcium. AB - 1. In the presence of 1.8 mM calcium (normal Tyrode's solution) increasing the potassium concentration significantly enhanced the phasic response of the rabbit detrusor muscle to 1 Hz field stimulation but did not affect either the tonic tension or the maximal rate of contraction. 2. At low calcium (0.6 mM) increasing the potassium concentration enhanced the phasic response to 1 and 4 Hz and significantly increased the tonic tension and the rate of tension generation. 3. Increasing the extracellular calcium concentration enhanced all parameters in a dose-dependent manner at all frequencies. The effect of increasing calcium was significantly greater at 1 and 4 Hz than at 32 Hz. Surface spectrofluorometry demonstrated that the increase in intracellular calcium stimulated by field stimulation paralleled the phasic contractile responses. 4. These results can be explained by potassium-induced increases in the intracellular bound calcium. PMID- 7875532 TI - Vanadate treatment reverses gastrointestinal complications in the streptozotocin diabetic rats. AB - 1. Insulin-like effects of vanadium compounds have been reported in various experimental conditions. Effects of vanadate on the decreased beta-adrenergic responsiveness of the rat duodenum due to streptozotocin diabetes were investigated to determine its influence on diabetic gastro-intestinal complications as well as its effects on the carbohydrate metabolism. 2. Administration of sodium orthovanadate to streptozoticin-diabetic rats in drinking water (0.7 mg/ml) for 4 weeks resulted in an improvement of carbohydrate metabolism noticed by increased serum levels of insulin and decreased blood levels of glucose as reported in previous studies. 3. Vanadate treatment of streptozotocin-diabetic rats also corrected the diabetic changes in the beta adrenergic responsiveness of the rat duodenum to salbutamol suggesting a beneficial effect on the diabetic complications of rat gastro-intestinal tract. The same treatment with vanadate did not cause any alteration in the beta adrenergic responsiveness of isolated duodenum from non-diabetic rats. 4. From the findings obtained, it is concluded that vanadate possesses an insulin-like effect on the beta-adrenergic responsiveness of the rat gastro-intestinal tract. Since vanadate treatment did not alter the beta-adrenergic responses of isolated duodenum from non-diabetic rats it seems likely that the insulin-like effect of vanadate is dependent on increased responsiveness of the gastrointestinal tract to circulating insulin. PMID- 7875533 TI - Inhibition of IL-1 release from human monocytes and suppression of streptococcal cell wall and adjuvant-induced arthritis in rats by an extract of Tripterygium wilfordii Hook. AB - 1. It was investigated whether an extract of Tripterygium wilfordii Hook f (TW) inhibits IL-1 production by monocytes and suppresses the development of IL-1 dependent arthritis induced in rats with streptococcal cell wall and adjuvant. 2. TW preferentially inhibited IL-1 alpha and IL-1 beta production by bacterial lipopolysaccharide (LPS)-stimulated human monocytes with IC50 of approximately 1 microgram/ml. 3. Oral administration of TW dose-dependently suppressed joint swelling and structural damage in streptococcal cell wall-induced arthritis (ED50 = 20 mg/kg/day) and in adjuvant-induced arthritis (ED50 = 46 mg/kg/day for developing and 8 mg/kg/day for established arthritis). PMID- 7875534 TI - Role of GABAA and GABAB receptors and peripheral cholinergic mechanisms in the antinociceptive action of taurine. AB - 1. Gabaergic and cholinergic mediation in the antinociceptive effect of taurine has been investigated in mice (acetic acid test) and rats (tail-flick test). 2. Scopolamine sulfate and methylnitrate exhibit intrinsic antinociceptive activity and increase the effect of taurine in mice. 3. Baclofen also increases the antinociceptive effect of taurine in mice. 4. Anticholinergic agents and bicuculline but not CGP 35348 antagonize the effect of taurine in rats. 5. These results suggest that the antinociceptive effect of taurine may be partly mediated by spinal GABAA receptors and peripheral cholinergic mechanisms. PMID- 7875535 TI - Modulation of substance P/neurokinin-1 receptor in human astrocytoma cells by antisense oligodeoxynucleotides. AB - 1. An antisense oligodeoxynucleotide corresponding to the NH2-terminus of the substance P (SP)/neurokinin-1 (SP/NK1) receptor was constructed and added to cultures of human astrocytoma U-87 MG cells in vitro and rats in vivo. 2. Antisense oligodeoxynucleotide at a concentration of 30 microM progressively reduced the specific binding [3H][Sar9, Met(O2)11]-SP, selective SP/NK1 receptor agonist, in the U-87 MG astrocytoma cells by approx. 31% on the second day after treatment (control: 26.1 +/- 2.4 fmol/mg protein vs antisense oligodeoxynucleotide: 18.0 +/- 1.4 fmol/mg protein, P < 0.001). 3. Treatment with 30 microM antisense oligodeoxynucleotide for 2 days inhibited the SP/MK1 receptor induced influx of 45Ca2+ into the U-87 MG cells by approx. 35%. 4. When the same antisense oligodeoxynucleotides were encapsulated in liposomes and injected into the lateral cerebral ventricle of rats, functional SP receptor was blocked. PMID- 7875536 TI - Functional and antiischemic effects of luteolin-7-glucoside in isolated rabbit hearts. AB - 1. The functional effects of the flavonoid luteolin-7-glucoside (LUT) were investigated in Langendorff-rabbit hearts perfused at constant pressure. Repetitive myocardial ischemia was induced by coronary artery ligature and quantified from NADH-fluorescence photography. 2. LUT significantly enhanced left ventricular pressure and the global and relative coronary flow (= global coronary flow/pressure-rate product). 3. LUT significantly diminished epicardial NADH fluorescence area and intensity. 4. LUT is an inodilator possessing cardioprotective properties. These might be related to an improvement of myocardial perfusion and/or to free radical scavenging properties. PMID- 7875537 TI - 5-HT4 receptors in rat but not guinea pig, rabbit or dog esophageal smooth muscle. AB - 1. Marked heterogeneity among species exists in the esophageal response to pharmacological agents. The present study compared the response to serotonin in esophagus from the rat, guinea pig, rabbit and dog. 2. The esophagus from all four species contracted to carbamylcholine and to PGF2 alpha; responses to serotonin were the most variable among species. 3. Serotonin contracted the guinea pig and rabbit esophagus; an effect blocked by LY53857 (10(-7 M) and ketanserin (10(-7) M), consistent with 5-HT2 receptor activation mediating this contraction. 4. Serotonin neither contracted nor relaxed the canine esophagus and relaxed the rat esophagus via 5-HT4 receptor activation as determined by antagonism with ICS 205-930 (-log KB = 6.4), metoclopramide (-log KB = 6.7) and its ester congener SDZ 205-557 (-log KB = 7.9). Two methylene homologs of SDZ 205 557 also had high 5-HT4 receptor affinity (-log KB = 7.7). 5. Thus, in guinea pig and rabbit esophagus, serotonin induced a contraction mediated by 5-HT2 receptors; and serotonin neither contracted nor relaxed the canine esophagus. In rat esophagus, serotonin induced a relaxation mediated by activation of 5-HT4 receptors. PMID- 7875538 TI - Vasoinhibitory effects of NC 1005 and NC 1006, new synthesized antiarrhythmic agents, in isolated rat aorta. AB - 1. NC 1005 and NC 1006 (3 x 10(-6) M-10(-4) M) inhibited the contractions induced by phenylephrine (PE) and KCl in isolated rat aortas with or without endothelium. 2. In a Ca(2+)-free medium containing EGTA and nifedipine, NC 1005 and NC 1006 inhibited PE-response and a subsequent response to Ca2+ in the presence of PE. 3. NC 1005 and NC 1006 also caused relaxations of endothelium-removed aortas precontracted with PE. 4. The relaxations induced by NC 1005 and NC 1006 were potentiated by amiloride, zaprinast and theophylline but not by increasing the external Na+ concentration. 5. Methylene blue and ouabain slightly potentiated NC 1005-relaxation, but not NC 1006-relaxation. 6. Glyburide, apamine and nifedipine had no effect on the relaxations. 7. NC 1005 and NC 1006 potentiated the relaxation induced by nitroglycerin (NG) without affecting isoproterenol relaxation. 8. In the presence of forskolin, NC 1005 and NC 1006 failed to potentiate NG-relaxation. 9. These results suggest that the vasoinhibitory effects of NC 1005 and NC 1006 may be due to an increase in the level of cAMP. PMID- 7875539 TI - Effects of human epidermal growth factor on passive avoidance and habituation learning in mice. AB - 1. Human epidermal growth factor (hEGF:0.02-2.0 micrograms) did not affect passive avoidance response or habituation learning when given before or immediately after training, or before retention. 2. hEGF (0.02-2.0 micrograms) failed to influence the scopolamine- or electroconvulsive shock-induced shortening of step-down latency in passive avoidance response when given before or immediately after training, or before retention. 3. These results suggest that the acute administration of hEGF does not affect memory processes as indexed by passive avoidance or habituation learning in normal or amnesic mice. PMID- 7875540 TI - Functional vascular renin-angiotensin system in hypertensive transgenic rats for the mouse renin gene Ren-2. AB - 1. Isolated aortic segments from transgenic rats for the mouse renin gene Ren-2 were more sensitive than those from control Sprague-Dawley ones to the vasoconstrictions induced by angiotensin II and to the potentiation of norepinephrine contractions by this peptide. 2. In transgenic, but not in control aorta, pretreatment with angiotensinogen potentiated norepinephrine-induced vasoconstrictions, this effect being abolished by captopril. 3. These results suggest that in the aorta of transgenic rats there is a higher functional tissue renin-angiotensin system that potentiates the vascular reactivity to norepinephrine. PMID- 7875541 TI - Vasospasmolytic effect of KRN2391 on 3,4-diaminopyridine-induced rhythmic contraction of porcine coronary artery. AB - 1. In the present study, we examined the vasospasmolytic effect of KRN2391 on rhythmic contractions of porcine coronary artery caused by 3,4-diaminopyridine (3,4-DAP) compared with cromakalim and nitroglycerin. 2. KRN2391 at 10(-7) showed a tendency to prolong the cycle length and at 10(-6) M completely eliminated rhythmic contractions in all preparations. The elimination by 10(-6) M KRN2391 was antagonized by either oxyhemoglobin (10(-5) M) or glibenclamide (3 x 10(-6)) although not completely. 3. Cromakalim at 10(-5) M and nitroglycerin at 10(-7) M completely eliminated 3,4-DAP-induced rythmic contractions in all preparations. The elimination by cromakalim and nitroglycerin was completely antagonized by glibenclamide and oxyhemoglobin, respectively. 4. The present study suggests that the vasospasmolytic effect of KRN2391 on 3,4-DAP-induced rhythmic contractions is based on its nitrate action and K channel opening action. PMID- 7875542 TI - Effect of multiple doses of volatile anesthetics on heme enzymes. AB - 1. The effect of the administration of several doses of Enflurane and Isoflurane (2 ml/kg, i.p., daily) on heme metabolism and glucose levels was studied. 2. Liver and kidney delta-Aminolevulinic acid synthetase (ALA-S) activities were 85% (P < 0.01) induced after the third dose of Enflurane, instead induction of this enzyme was only detected, in animals receiving one dose of Isoflurane. 3. Blood Porphobilinogenase and deaminase (50%, P < 0.01) inhibition was produced only when animals received a single dose of the anesthetics. 5. ALA-S induction observed after the third dose of anesthetics could be a consequence of long lasting depletion in heme synthesis produced by blocking at uroporphyrinogen level. PMID- 7875543 TI - Nephrotoxicity of gentamicin and co-trimoxazole combination in rats. AB - 1. The nephrotoxicity of gentamicin is well known. However, little information is available regarding the combined effects of gentamicin plus co-trimoxazole (sulfamethoxazole-trimethoprim). Therefore, Wistar rats were treated daily with 100 mg/kg gentamicin or 100 mg/kg gentamicin plus 30 mg/kg trimethoprim-150 mg/kg sulfamethoxazole for 14 days. 2. Serum biochemical parameters were measured on days 0, 8 and 15, and histopathological examinations of kidneys were performed on day 15, one day following end of treatment. Gentamicin treated rats exhibited a 63% increase in blood urea nitrogen (BUN), a 124% increase in uric acid, and a 63% decrease in serum potassium levels on day 15. 3. The combination of gentamicin plus co-trimoxazole partially ameliorated these effects. With the three drug combination no change occurred in BUN, and only a 30% decrease occurred in serum potassium levels. 4. While serum creatinine levels significantly increased following gentamicin, the co-administration of co trimoxazole resulted in a significant decrease (30%) in creatinine. Histopathological examinations of kidneys suggested a lower degree of nephrotoxicity in rats treated with gentamicin plus co-trimoxazole as compared to animals treated with gentamicin alone. 5. The results support the importance of monitoring serum biochemical parameters when treating with gentamicin or gentamicin plus co-trimoxazole. PMID- 7875544 TI - Direct inotropic action of WB-4101 and prazosin in the guinea pig papillary muscle. Comparison with HOE-234, the new activator of ATP-sensitive K+ channels. AB - 1. The alpha-1a adrenoceptor antagonist WB-4101, the alpha-1 adrenoceptor antagonist prazosin and the new activator of ATP-sensitive K+ channels HOE-234 were examined. The force of contraction and the rate of rise of contraction force were measured. 2. WB-4101 and HOE-234 were found to produce negative inotropic action in a dose dependent manner. This effect was attenuated by glibenclamide. On the other hand prazosin increased slightly the force of contraction and the rate of rise of contraction force in the same tissue. 3. The direct inotropic effects of above mentioned substances are compared and discussed. PMID- 7875545 TI - Different influence of superoxide anions and hydrogen peroxide on endothelial function of isolated cat cerebral and pulmonary arteries. AB - 1. Exogenous superoxide dismutase (SOD) or catalase did not modify isolated cat middle cerebral arterial basal tone. Catalase but not SOD reduced ACh relaxation. 2. H2O2 induced endothelium-independent relaxation which was abolished by catalase. 3. 3-Amino-1,2,4-triazole (AT) evoked endothelium-dependent contractions and diminished ACh relaxation. 4. Diethyldithio carbamic acid (DETC) induced endothelium-independent relaxation and did not modify ACh vasodilatation. 5. ACh relaxation of cat isolated pulmonary arteries was unaffected by SOD, catalase or AT, and diminished by DETC. 6. Endothelial catalase but neither SOD nor superoxide anions is involved in EDRF cerebral vasodilatation and H2O2 participates in ACh relaxation. In pulmonary arteries, only endothelial SOD activity plays a role. PMID- 7875546 TI - Salt preference elicited by chronic intracerebroventricular angiotensin II. AB - 1. Much more water was consumed than either 0.9% or 2.7% saline in response to various dipsogenic stimuli in untreated normal replete rats when they had free access to water, 0.9% and 2.7% saline. On the other hand, the rats drank more 0.9% saline than water and 2.7% saline when each solution is the sole drinking fluid offered. 2. A marked increase in preference for 0.9% saline was observed during the chronic i.c.v. injection of angiotensin II at a dose of 25 ng/hr for 7 consecutive days in the three bottle choice test. After the cessation of angiotensin II infusion, most rats (45 out of 50 rats) returned to drink much more water than 0.9% and 2.7% saline, similar to the drinking pattern of the 0.9% saline-treated control rats. However, some rats (5 out of 50 rats) still preferred 0.9% saline and this persisted for up to 3 months although these rats did not show a hypertensive state and an increase of plasma renin activity. PMID- 7875547 TI - Antisecretory and gastroprotective effects of aescine in rats. AB - 1. This study was designed to determine the antisecretory effects of aescine in the perfused stomach of the anaesthetized rat. In addition, the effects of aescine on mucosal lesions produced by intragastric instillation of 1 ml of absolute ethanol, its action on the production of mucus and the possible role of PGs in aescine induced gastroprotection were also studied. 2. Pretreatment of aescine (10 and 50 mg/kg) inhibited the increases in acid secretion induced by histamine (5 mg/kg) and carbachol (10 micrograms/kg). At the highest dose used abolished nearly the increase induced by carbachol (P < 0.001). 3. Aescine (10, 25 and 50 mg/kg) was found to be effective in the prevention of gastric ulceration induced by absolute ethanol in rats. The degree of gastroprotection decreased with time, the optime effects occurring 60-120 min after oral administration. Pretreatment with indomethacin (10 mg/kg) partially inhibited the gastric protection but the PGE2 determination did not show an increase in prostanoid levels. Furthermore, the protective effect was not associated with an increase in the amount of gastric mucus and glycoprotein content. 4. These results indicate that aescine exerts an antisecretory action which could play a possible role in its antiulcerogentic activity. Also it shows a marked protective mucosal activity which could be partly explained through non-prostaglandin dependent mechanisms involving its antiinflammatory and vasoactive properties. PMID- 7875548 TI - Effects of chronic diabetes on the responsiveness to endothelin-1 and other agents of rat atria and thoracic aorta. AB - 1. Plasma endothelin-1 level as well as plasma lipid and glucose levels was markedly elevated in the rats treated with streptozotocin 8 weeks earlier. 2. Positive inotropic response, which was significantly greater than that in the age matched control, was produced by endothelin-1 in the left atria isolated from diabetic rats. On the other hand, the contractile response of thoracic aorta to endothelin-1 was conversely attenuated in the diabetic rats. Such contrasting effects of diabetes between the atrial and aortic muscles were observed in the responsiveness to other contractile drugs. Endothelium-dependent relaxation in the thoracic aorta was also significantly attenuated in diabetic rats. However, the basal twitch contraction of left atria, the chronotropic responses to endothelin-1, isoproterenol and carbachol and the relaxation of the aorta by papaverine were not affected by diabetes. 3. These results suggest that the contractile responsiveness of atrial and aortic muscles and the endothelial functions significantly alter during diabetes for 8 weeks. PMID- 7875549 TI - Identification of factors mediating the decrease of alkaline phosphatase activity caused by tension-force in periodontal ligament cells. AB - 1. We examined the factors which mediate the decrease of alkaline phosphatase (ALP) activity in human peridontal ligament (PDL) cells in response to cyclic tension-force. 2. ALP activity in human PDL cells obtained from three donors in response to cyclic tension-force (24% elongation) was 43% lower than that of the corresponding control. 3. ALP activity was decreased by the addition of conditioned medium obtained from the culture of the cells exposed to tension force. 4. The inhibitory effect of the conditioned medium on ALP activity was partially abolished in the presence of indomethacin (10(-6) M) and IL-1 beta antibody (10 ng/well). Moreover it was almost completely abolished in the presence of both indomethacin and IL-1 beta antibody. 5. Treatment of PDL cells with exogenous PGE2 or IL-1 beta for 24 hr caused a dose-dependent decrease in ALP activity. Treatment with both PGE2 (10(-8) M) and IL-1 beta (1.25 x 10(-10) M) together decreased ALP activity by 47% compared with the non-treated control. 6. These findings suggest that ALP activity in PDL cells was decreased in response to the cyclic tension-force and that the decrease in ALP activity was mainly mediated by PGE2 and IL-1 beta produced by PDL cells in response to cyclic tension-force. PMID- 7875550 TI - Oral administration of quercitrin modifies intestinal oxidative status in rats. AB - 1. Oral administration of quercitrin to rats for 3 days increases the mucosal glutathione contents in ileum and colon as well as inhibits non-enzymatic lipid peroxidation induced in membrane fractions from jejunal and colonic mucosa. 2. After 7 days of treatment with quercitrin, rat intestinal oxidative status trends to normalize to control rats. PMID- 7875551 TI - Effect of the sulfonylurea glyburide on glycogen synthase activity in alloxan induced diabetic rat adipocytes. AB - 1. The effect of glyburide (glibenclamide) treatment in vivo on the adipose tissue glycogen synthase activity of type II diabetic rats has been studied. 2. Three week treatment of diabetic animals with glyburide (5 mg/kg orally, in saline) increased adipose glycogen synthase activity and decreased blood glucose levels. 3. These results demonstrate that the sulfonylurea glyburide is capable of exerting direct insulin-like effect on adipose glycogen-synthase activity of type II diabetic rats in vivo. PMID- 7875552 TI - Influence of iron, deferoxamine and ascorbic acid on gentamicin-induced nephrotoxicity in rats. AB - 1. Nephrotoxicity was induced in rats by injecting gentamicin intramuscularly (i.m.) at a dose of 80 mg/kg for 6 days. Treated animals demonstrated a typical pattern of nephrotoxicity characterized by increased serum creatinine and urea concentrations, and by necrosis of proximal tubular epithelium. 2. Pretreatment of rats with iron (Fe3+) at daily i.m. doses of 2, 4 and 8 mg/kg for 14 days, with gentamicin given during the last 6 days of treatment, significantly potentiated the gentamicin-induced increases in creatinine and urea concentrations and exacerbated renal histological damage. 3. Gentamicin significantly increased serum Fe3+ concentration in rats treated with Fe3+ and gentamicin, compared to Fe(3+)-treated rats. 4. The Fe3+ antidote deferoxamine (100 mg/kg, i.m.) given with gentamicin was ineffective in antagonizing the potentiating effect of Fe3+ on gentamicin-induced nephrotoxicity. 5. Ascorbic acid (50 mg/kg, i.m. for 14 days) was ineffective in altering the nephrotoxicity of gentamicin (80 mg/kg) given during the last 6 days of treatment. At a dose of 100 mg/kg for 14 days, ascorbic acid significantly reduced gentamicin-induced increases in creatinine and urea levels, and ameliorated proximal tubular damage. However, at a dose of 200 mg/kg, ascorbic acid exacerbated gentamicin-induced increases in creatinine and urea levels and increased the severity of the histological damage. PMID- 7875553 TI - The hypotensive effect of cisapride in rat. AB - 1. Cisapride is a prokinetic agent believed to facilitate acetylcholine release from the myenteric plexus of the gut. The aim of the present study was to investigate the effect of cisapride on blood pressure and the effects of muscarinic receptor antagonists on the cisapride-induced blood pressure changes. 2. Cisapride was given i.v. alone or 10 min after muscarinic receptor antagonists. Cisapride given i.v. produced a significant decrease in blood pressure in a dose-related manner. Atropine, AF-DX 116 and 4-DAMP given 10 min before cisapride injection, partially inhibited the hypotensive response to cisapride. In pithed rat, the effect of cisapride on blood pressure remained unaltered. 3. This study indicates that the action of cisapride is not through central mechanisms and part of cisapride's effect is through the cholinergic system. PMID- 7875554 TI - Serotonin-induced decrease in brain ATP, stimulation of brain anaerobic glycolysis and elevation of plasma hemoglobin; the protective action of calmodulin antagonists. AB - 1. Injection of serotonin (5-hydroxytryptamine) to rats, induced a dramatic fall in brain ATP level, accompanied by an increase in P(i). Concomitant to these changes, the activity of cytosolic phosphofructokinase, the rate-limiting enzyme of glycolysis, was significantly enhanced. Stimulation of anaerobic glycolysis was also reflected by a marked increase in lactate content in brain. 2. Brain glucose 1,6-bisphosphate level was decreased, whereas fructose 2,6-bisphosphate was unaffected by serotonin. 3. All these serotonin-induced changes in brain, which are characteristic for cerebral ischemia, were prevented by treatment with the calmodulin (CaM) antagonists, trifluoperazine or thioridazine. 4. Injection of serotonin also induced a marked elevation of plasma hemoglobin, reflecting lysed erythrocytes, which was also prevented by treatment with the CaM antagonists. 5. The present results suggest that CaM antagonists may be effective drugs in treatment of many pathological conditions and diseases in which plasma serotonin levels are known to increase. PMID- 7875555 TI - Effects of carbaryl on some dopaminergic behaviors in rats. AB - 1. The effects of acute oral administration of carbaryl (10-80 mg/kg), a carbamate insecticide, on some experimental models for detecting dopaminergic activity were examined in rats. Also, serum biochemical variables following carbaryl treatments were determined. 2. Carbaryl (20 and 40 mg/kg) significantly increased the number of apomorphine-induced yawns and at dose of 80 mg/kg it prolonged the duration time of haloperidol-induced catalepsy. Pretreatment with carbaryl failed to affect apomorphine-induced stereotypes. 3. Carbaryl significantly reduced blood cholinesterase activity and elevated blood glucose levels and SGOT and SGPT activities. 4. These results indicate that low oral doses of carbaryl can cause behavioral and toxicological effects in rats. PMID- 7875556 TI - GABAergic and dopaminergic systems may be involved in seizures induced by pyrimethamine in mice. AB - 1. The effects of some GABAergic and dopaminergic agents on pyrimethamine-induced tonic seizures were investigated in mice. 2. Pyrimethamine dose dependently induced seizures in mice. 3. Muscimol, AOAA and DABA significantly protected mice against pyrimethamine-induced seizures. 4. Bicuculline and picrotoxin effectively potentiated seizures elicited by pyrimethamine and significantly antagonized the protective effect of muscimol against the seizures. 5. Diazepam and phenobarbitone effectively protected mice against seizures elicited by pyrimethamine. 6. L-Dopa significantly potentiated pyrimethamine-induced seizures. 7. Apomorphine and pargyline significantly reduced the latency of seizures induced by pyrimethamine. 8. Haloperidol and pimozide effectively protected mice against pyrimethamine-elicited seizures and also significantly antagonized the potentiating effects of apomorphine and L-dopa on the seizures. 9. Disulfiram significantly potentiated seizures induced by pyrimethamine and also significantly enhanced the seizure-potentiating effect of L-dopa. 10. alpha Methyl-p-tyrosine effectively protected against seizures induced by pyrimethamine. However, L-dopa significantly potentiated the seizures in alpha methyl-p-tyrosine-pretreated animals. 11. Muscimol significantly attenuated the potentiating effect of L-dopa on pyrimethamine-induced seizures while bicuculline significantly enhanced the effect of L-dopa. Furthermore, haloperidol significantly potentiated the protective effect of muscimol against pyrimethamine induced seizures. 12. These results suggest that both GABA and dopamine might be involved in the mechanism(s) of pyrimethamine seizures in mice. PMID- 7875557 TI - Modulation of brainstem 5-HT1C receptors by serotonergic drugs in the rat. AB - 1. The sparse population of brainstem 5-hydroxytryptamine1C (5-HT1C) (also called 5-HT2C) receptors has received little attention despite its possible role in the serotonin syndrome and 5-HT-mediated shaking behavior. We characterized [3H]mesulergine binding in rat brainstem and, to determine if brainstem 5-HT1C sites respond to serotonergic manipulations, performed saturation studies of [3H]mesulergine binding in brainstem from rats treated chronically with 11 different 5-HT1C/2 agonists and antagonists. 2. In competition studies in vitro, the rank order of drug potency was most compatible with a 5-HT1C receptor binding site: mianserin, 5-HT, cinanserin, 1-(3-chlorophenyl)piperazine (m-CPP), 1-(2-5 dimethoxy-4-iodophenyl)-2-aminopropane (DOI), MDL 100,907, RU 24969, 5 carboxamidotryptamine (5-CT), 8-OH-DPAT, MDL 72,222. 3. Chronic treatment with the agonists quipazine and trifluoromethylphenylpiperazine (TFMPP) and the antagonists ritanserin and methiothepin significantly down-regulated brainstem 5 HT1C sites, which were 65% of [3H]mesulergine-labeled sites in brainstem. Only metergoline and ritanserin significantly increased pKD. 4. Chronic treatment in vivo with DOI, m-CPP, mianserin, methysergide, spiperone, cyproheptadine, and metergoline had no significant effect on BMAX at the dose studied. 5. These data suggest similarities in the regulation of 5-HT1C and 5-HT2 sites at which both 5 HT1C 2 agonists and antagonists also induce receptor down-regulation. 6. 5-HT1C/2 agonists and antagonists that did not down-regulate brainstem 5-HT1C sites may be more active in vivo at 5-HT2 sites, at 5-HT1C sites in other brain regions, have effects on 5-HT1C receptors not detectable at the recognition site, or differ for pharmacokinetic reasons. PMID- 7875558 TI - Molecular biology of yeast exoglucanases. AB - Three exoglucanase (Exg) genes have been reported in Saccharomyces cerevisiae. Gene EXG1 encodes the major isoenzyme (ExgI). Differential glycosylation of the primary translation product throughout the secretory pathway results in the secretion of several glycoforms. The major glycoform (ExgIb) contains two short carboxypeptidase Y-like oligosaccharides attached to both potential glycosylation sites present in the molecule. A minor glycoform (ExgIa) arises from the former by elongation of the second oligosaccharide. The protein portion is processed in the secretory pathway by the Kex2 protease. Gene EXG2 encodes a 63 kDa polypeptide with 12 potential glycosylation sites. The predicted protein, ExgII, carries a signal peptide at the amino terminus and a glycosyl-phosphatidyl inositol anchoring motif at the carboxyl end. The latter appears responsible for the particulate nature of this isoenzyme, since its elimination results in the secretion of this activity into the culture medium. Gene SSG1 encodes a 52 kDa polypeptide which is specifically synthesized during sporulation of diploids. SSG1 expression is under control of both sexual (a1-alpha 2 element) and nutritional control. Although homozygous ssg1/ssg1 diploid strains are still able to complete sporulation, they exhibited a delay in the appearance of mature asci. Single or double disruption of EXG1 and EXG2 did not result in any relevant phenotype and the triple mutant behaved as ssg1/ssg1. A ExgI-related enzyme is secreted by Candida albicans. All these four enzymes share 8 highly conserved regions in the same relative positions, indicating that they derived from a common ancestor. However, no clear function has so far been demonstrated for them. PMID- 7875559 TI - Differential synthesis of glyceraldehyde-3-phosphate dehydrogenase polypeptides in stressed yeast cells. AB - Three unlinked genes, TDH1, TDH2 and TDH3, encode the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (triose-phosphate dehydrogenase; TDH) in the yeast Saccharomyces cerevisiae. We demonstrate that the synthesis of the three encoded TDH polypeptides (TDHa, TDHb and TDHc, respectively) is not co ordinately regulated and that TDHa is only synthesised as cells enter stationary phase, due to glucose starvation, or in heat-shocked cells. Furthermore, the synthesis of TDHb, but not TDHc, is strongly repressed by a heat shock. Hence, the TDHa enzyme may play a cellular role, distinct from glycolysis, that is required by stressed cells. PMID- 7875560 TI - Isolation of genes encoding beta-D-xylanase, beta-D-xylosidase and alpha-L arabinofuranosidase activities from the rumen bacterium Prevotella ruminicola B1(4). AB - Prevotella ruminicola B1(4) is a strictly anaerobic, Gram-negative, polysaccharide-degrading rumen bacterium. Xylanase activity in this strain was found to be inducible, the specific activity of cells grown on xylan being increased at least 20-fold by comparison with cells grown on glucose. Ten bacteriophage clones expressing xylanase activity were isolated from a lambda EMBL3 genomic DNA library of P. ruminicola B1(4). These clones were shown to represent four distinct chromosomal regions, based on restriction enzyme analysis and DNA hybridisation. Three groups of clones encoded activity against oat spelt xylan but not carboxymethylcellulose (CMC). In one of these groups, represented by clone 5, activities against pNP-arabinofuranoside and pNP-xyloside were found to be encoded separately from endoxylanase activity. The fourth region encoded activity against CM cellulose and lichen, in addition to xylan, and contains an endoglucanase/xylanase gene isolated previously. PMID- 7875561 TI - Cell wall anchoring to cytoplasmic membrane of Candida albicans. AB - Cell wall ultrastructure of the opportunistic pathogenic yeast Candida albicans was investigated by stereoscopic freeze-etching technique. Three wall layers were distinguishable by this technique. No clear periplasmic space was evident. Bilayer membrane invaginations were extensive. The outermost regions of the membrane invaginations were lined with thin, spine-like fibrils, which extended into the cell wall. We suggest that the fibrils along the invaginations are involved in anchoring the cell wall to the membrane. PMID- 7875562 TI - rRNA operon restriction derived taxa for Streptomyces (RiDiTS). AB - A method for grouping Streptomyces strains by fingerprints of their rRNA operons is described. In polyacrylamide gels, multicopy rRNA operon fragments in Streptomyces genomic MseI fingerprints produced intense bands which are well resolved from the less conspicuous low copy fragments interspersed between them. The high intensity multicopy rRNA bands are easily distinguished from the low intensity bands, eliminating the need for Southern blot hybridization to visualize the rRNA fragments. Direct evidence that the high-intensity bands in these polyacrylamide gels originated from rRNA operons was provided by a 'differential' Southern blot technique. We have used this method to assign 98 strains to 11 rRNA fingerprint type groups. This clustering method may be applicable to any prokaryote with a high G+C content genome. PMID- 7875563 TI - Isolation from recombinant Escherichia coli and characterization of CMP-Kdo synthetase, involved in the expression of the capsular K5 polysaccharide (K-CKS). AB - In Escherichia coli with group II capsules, the synthesis of capsular polysaccharide and its cellular expression are encoded by the kps gene cluster, which is composed of three regions. The central region 2 encodes proteins involved in polysaccharide synthesis, and the flanking regions 1 and 3 direct the translocation of the finished polysaccharide across the cytoplasmic membrane and its surface expression. The kps genes of E. coli with the group II capsular K5 polysaccharide, have been cloned and sequenced. Region 1 contains the kpsE, D, U, C and S genes. In this communication we describe the overexpression of the kpsD and kpsU genes as well as the isolation of the KpsU protein from the recombinant bacteria by chloroform treatment. The purified KpsU protein exhibited CMP-Kdo synthetase activity. The N-terminal sequence and two internal peptide sequences of the isolated protein are in agreement with that previously predicted from the DNA sequence of the kpsU gene. The kinetic data of the CMP-Kdo-synthetase participating in K5 capsule expression (K-CMP-Kdo-synthetase) differ from those described for the CMP-Kdo-synthetase, participating in lipopolysaccharide synthesis (L-CMP-Kdo-synthetase). PMID- 7875564 TI - vanA-mediated high-level glycopeptide resistance in Enterococcus faecium from animal husbandry. AB - Glycopeptide-resistant Enterococcus faecium strains were isolated from a pig farm and a poultry farm both using avoparcin as a food additive. Such organisms were not isolated in a hen's eggs-producing farm not using avoparcin. Glycopeptide resistant enterococci were also detected in broiler chicken carcasses that were delivered to a hospital's kitchen. The resistance was determined by the vanA gene as indicated by the detection of the inducible 39-kDa cytoplasmic membrane protein and of a vanA-specific DNA sequence amplified by polymerase chain reaction. Genomic DNA fragment patterns of strains from animal sources were different from each other and also from those of strains isolated in hospitals and from sewage treatment plants. This findings suggest the dissemination of the vanA determinant among different enterococcal strains of distinct ecological origin. PMID- 7875565 TI - Role of DegP protease on levels of various forms of colicin A lysis protein. AB - The total amount of the colicin A lysis protein produced by cells grown in rich medium was analysed by immunoblotting. The intermediate forms of synthesis of this small lipoprotein were present in the cells at any time of induction, confirming that processing and maturation of colicin A lysis protein are slow and incomplete processes. The level of these various forms varied according to the time of induction, the growth conditions, the producing strain and the plasmid carrying the cal gene. It depended mainly on the presence in the producing strain of a degP gene which encodes the DegP protease. According to growth conditions, the DegP protease hydrolysed either a part or the total amount of the acylated precursor form. In some cases, a protease(s) other than DegP seemed to act on either form(s) of the colicin A lysis protein. PMID- 7875566 TI - Structure and transcription of genes within the beta-hbd-adh1 region of Clostridium acetobutylicum P262. AB - The 1.2-kb DNA fragment upstream of the linked beta-hbd (3-hydroxybutyryl-CoA dehydrogenase) and adh1 (NADPH-dependent alcohol dehydrogenase) genes from Clostridium acetobutylicum P262 was sequenced. The upstream region contained an open reading frame (ORFB) which was found to have 44% amino acid identity to the fixB gene products of Rhizobium and Azorhizobium. The beta-hbd and ORFB genes were expressed during the acidogenic and solventogenic phases. The beta-hbd gene was transcribed on a single mRNA species of 2.0 kb, whereas the ORFB gene was transcribed on two species of mRNA of 2.0 and 3.5 kb, respectively. The adh1 gene was induced or derepressed at the pH breakpoint before the onset of solventogenesis and was transcribed on a single species of mRNA of 2.4 kb. PMID- 7875567 TI - Detection and differentiation of the gene for toxin co-regulated pili (tcpA) in Vibrio cholerae non-O1 using the polymerase chain reaction. AB - The polymerase chain reaction has been used to differentiate the gene which encodes the toxin co-regulated pili (tcpA) of the El Tor and classical biotypes of Vibrio cholerae O1. The same PCR primers were applied to strains belonging to non-O1 serogroups that produced cholera toxin. The size of fragment amplified was either identical to the tcpA of biotype El Tor (471 bp) or to the tcpA of biotype classical (617 bp). All strains belonging to the novel epidemic serogroup O139 generated a 471-bp fragment identical to El Tor tcpA. The present study suggests that there may be an association between non-O1 serogroup and tcpA type. PMID- 7875568 TI - Cloning of a cuticle-degrading protease from the entomopathogenic fungus, Beauveria bassiana. AB - A Beauveria bassiana extracellular subtilisin-like serine endoprotease is a potential virulence factor by virtue of its activity against insect cuticles. A cDNA clone of the protease was isolated from mycelia of B. bassiana grown on cuticle/chitin cultures. The amino acid sequence of this gene was compared to that of Metarhizium anisopliae Pr1, the only pathogenicity determinant so far described from an entomopathogenic fungus, and proteinase K, isolated from Tritirachium album, a saprophytic fungus. The cDNA sequence revealed that B. bassiana Pr1 is synthesized as a large precursor (M(r) 37,460) containing a signal peptide, a propeptide and the mature protein predicted to have an M(r) of 26,832. PMID- 7875569 TI - Distribution of the flavohaemoglobin, HMP, between periplasm and cytoplasm in Escherichia coli. AB - The subcellular distribution of the soluble flavohaemoglobin (HMP) of Escherichia coli has been determined. Cells over-expressing HMP from the cloned hmp gene on a multicopy plasmid were fractionated by osmotic shock and lysozyme treatment. Spectral analysis of subcellular fractions showed the CO-binding haemoprotein to be cytoplasmic. However, Western blotting using antibody raised to purified HMP revealed approximately 30% of the protein to be periplasmic in the over expressing strain. Western analysis also revealed substantial levels of periplasmic HMP in a strain expressing only chromosomally encoded protein but none in an hmp mutant. The results are discussed in relation to protein function and the similar distribution reported for Vitreoscilla globin. PMID- 7875570 TI - Polymerase chain reaction for identification of human and porcine spirochaetes recovered from cases of intestinal spirochaetosis. AB - A polymerase chain reaction (PCR) amplification of 16S rDNA was developed to identify spirochaetes recovered from cases of intestinal spirochaetosis in humans and pigs; these bacteria belong to a distinct genetic group of spirochaetes, with the proposed name 'Anguillina coli'. The PCR incorporated a universal eubacterial 16S rDNA sequencing primer (1492r), and a 21-base forward primer designed to include a nucleotide sequence specific for 'A. coli'. The PCR was used to correctly identify DNA extracted from 43 isolates of 'A. coli' from humans and pigs, whilst no product was produced from Escherichia coli, or from other intestinal spirochaetes, including 38 isolates of Serpulina spp., and one each of Treponema succinifaciens and Brachyspira aalborgi. The amplification provided a rapid and simple means of identifying DNA from isolates of 'A. coli', and could be used on boiled whole 'A. coli' cells, with a detection limit equivalent to 2.5 x 10(2) cells. The reaction was used to detect and identify these spirochaetes from selective agar plates inoculated with stool specimens from infected pigs. PMID- 7875571 TI - Specificity and effectivity in nodulation by Frankia on southern hemisphere actinorhiza. AB - Nodulation ability was tested for Frankia strains HFPCcI3 and EL1, and Frankia sources A.t. and G.a. from Allocasaurina torulosa and Gymnostoma australianum, respectively, on A. torulosa Miq., Casuarina cunninghamiana Miq., G. australianum L. Johnson and Elaeagnus triflora Roxb. It was shown that A. torulosa and C. cunninghamiana formed nodules only with the Frankia sources obtained from their own host plant, while E. triflora formed nodules with three of the four Frankia sources tested. All nodules formed were effectively fixing nitrogen. Specific nitrogenase activity was highest in E. triflora inoculated with the Frankia strain isolated from nodules of the same species. Identification of Frankia sources in the nodules was performed by use of PCR amplification of DNA with a random primer. PCR amplification of DNA isolated from nodules of G. australianum and E. triflora inoculated with Frankia strain EL1 revealed, when compared with DNA amplified from free living Frankia strain EL1, that there was only one Frankia strain causing the observed nodules. PMID- 7875572 TI - Cloning, sequencing and characterization of the alkaline phosphatase gene (phoD) from Zymomonas mobilis. AB - The phoD gene encoding the membrane-bound alkaline phosphatase (ALPI) from Zymomonas mobilis CP4 was cloned and sequenced. Both the translated sequence and the properties of the recombinant enzyme were unusual. Z. mobilis ALPI was monomeric (M(r) 62,926) and hydrolysed nucleotides more effectively than sugar phosphates. The translated sequence contained a single hydrophobic segment near the N-terminus which may serve as a membrane-anchor in Z. mobilis, although the recombinant enzyme was recovered in the cytoplasmic fraction of Escherichia coli. The predicted amino acid sequence for ALPI did not align well with other ALPs or other known genes. However, some similarity to E. coli ALP was noted in the metal binding and phosphate-binding regions. Two other regions were identified with similarity to the active sites of pyruvate kinase and mammalian 5'-nucleotide phosphodiesterase (also membrane-bound), respectively. It is likely that Z. mobilis phoD represents a new class of alkaline phosphatase genes which has not been described previously. PMID- 7875573 TI - Identification and characterization of specific sequences encoding pathogenicity associated proteins in the genome of commensal Neisseria species. AB - The distribution of distinct sequences in pathogenic and commensal Neisseria species was investigated systematically by dot blot analysis. Probes representing the genes of Rmp, pilin and IgA1 protease were found to hybridize exclusively to the chromosomal DNA of the pathogenic species, Neisseria gonorrhoeae and/or Neisseria meningitidis. In contrast, specific sequences for the genes of the porin protein Por and the opacity protein (Opa) were also detected in a panel of commensal Neisseria species such as N. lactamica, N. subflava, N. flava, N. mucosa and N. sicca. Using opa-specific oligonucleotides as probes in chromosomal blots, the genomes of the commensal Neisseria species show a totally reduced repertoire of cross-hybridizing loci compared to the complex opa gene family of N. gonorrhoeae. DNA sequence analysis of one opa-related gene derived from N. flava and N. sicca, respectively, revealed a large degree of homology with previously described gonococcal and meningococcal genes, e.g., a typical repetitive sequence in the leader peptide and the distribution of the hypervariable and conserved regions. This observation, together with the finding, that the gene is constitutively transcribed, leads to the assumption that some of the commensal Neisseria species may have the potential for the expression of a protein harboring similar functions as the Opa proteins in pathogenic Neisseriae. PMID- 7875574 TI - Comparison of type IV-pilin genes of Pseudomonas aeruginosa of various habitats has uncovered a novel unusual sequence. AB - All known pilin sequences in Pseudomonas aeruginosa were amplified by a set of consensus primers located in the 5"-conserved region of pilA and the threonine specific t-RNA following pilA. This also enabled the discovery of a novel pilin gene in a strain pair of clonal variants, which differs from known pilin genes in its increased GC-content. The mature protein has 173 amino acids making it the longest pilin known to date in P. aeruginosa. Different inserted sequences detected between the 3"-end of the pilin gene and the t-RNA in this strain and in strains with group I pilin genes seemed to be specific for each pilin group indicating a horizontal cotransfer of sequences. PMID- 7875575 TI - A new plasmid (QpDV) common to Coxiella burnetii isolates associated with acute and chronic Q fever. AB - Genetic studies of Coxiella burnetii strains suggested the possibility of differentiating new isolates according to their plasmid DNA content. Virulence and/or clinical manifestations ('chronic' and 'acute' Q fever) had been claimed to correlate with this plasmid typing. A new plasmid, named QpDV, was found to be common to C. burnetii isolates obtained from acute and chronic Q fever. According to the results obtained, plasmid usage for detection and differentiation of respective pathovars of C. burnetii and the correlation between gene specificity and pathovar has to be revised. Closer studies suggested a common origin of C. burnetii plasmids, but also showed some differences characteristic for each plasmid, probably reflecting divergent evolution. PMID- 7875577 TI - Transformation of Aspergillus nidulans by microprojectile bombardment on intact conidia. AB - This paper describes transformation of intact conidia of Aspergillus nidulans, auxotrophic for arginine, by using the biolistic process. The plasmid employed was pFB39, carrying the argB gene. The transformation frequency obtained was 81 transformants/microgram of DNA. Classical genetics and molecular analysis were conducted to analyse transformants and to determine in which chromosome integration took place. PMID- 7875576 TI - Cloning and sequencing of the pac gene encoding the penicillin G acylase of Bacillus megaterium ATCC 14945. AB - The pac gene encoding the penicillin G acylase (PGA) of Bacillus megaterium ATCC 14945 has been cloned in Escherichia coli HB101 (proA, leuB) using a selective minimal medium containing phenylacetyl-L-leucine instead of L-leucine. The nucleotide sequence of this gene has been determined and contains an open reading frame of 2406 nucleotides. The deduced amino acid sequence shows significant similarity with other beta-lactam acylases. Although the PGA of B. megaterium is extracellular, the enzyme produced in E. coli appears to have a cytoplasmic localization. PMID- 7875578 TI - Phylogenetic position of Rickettsia tsutsugamushi and the relationship among its antigenic variants by analyses of 16S rRNA gene sequences. AB - The 16S rRNA gene sequences of Rickettsia tsutsugamushi and Rickettsia sibirica were determined by PCR and DNA sequencing. Phylogenetic analysis revealed that R. sibirica is positioned in a cluster of the genus Rickettsia with a similarity value of 98.1-99.6%, whereas R. tsutsugamushi is located apart from the cluster with a similarity value of 90.2-90.6%. This evidence suggests that R. tsutsugamushi should be excluded taxonomically from the genus Rickettsia. The phylogenetic classification of six antigenic variants in R. tsutsugamushi moderately reflected their antigenic relationship known in closely and distantly related strains. PMID- 7875579 TI - The effect of carbohydrates on the expression of the Prevotella ruminicola 1,4 beta-D-endoglucanase. AB - The beta-1,4-endoglucanase of the ruminal bacterium, Prevotella ruminicola B14, hydrolysed carboxymethylcellulose and barley glucan but not xylan or mannan. Endoglucanase activity was present in 88- and 82-kDa proteins, and there was at least a 20-fold variation in endoglucanase activity when P. ruminicola B14 was grown on different sugars. The highest activities were observed with mannose, cellobiose or xylose and little activity was observed with sucrose, arabinose or rhamnose, P. ruminicola B14 also had significant xylanase and mannanase activities, but these activities were present in proteins that had lower molecular masses than the endoglucanase and these proteins did not cross-react with antibody made against the endoglucanase. Mannanase activity has a similar pattern of expression to the endoglucanase, while the xylanase was not induced or repressed by the same sugars or combinations of sugars. The xylanase activity was greatest when xylan was the energy source for growth, but xylose was a very poor inducer of xylanase activity. PMID- 7875580 TI - Novel helper phage design: intergenic region affects the assembly of bacteriophages and the size of antibody libraries. AB - Phagemid vectors for display of protein/peptides on the surface of filamentous phage utilize a plasmid genome carrying the phage origin of replication, along with the gene fused to a fragment of gene III. Generation of phage particles displaying the fusion protein also requires superinfection of the host bacterium with a helper virus. We describe here the construction of a new gene III mutant of M13 KO7 bacteriophage and compare its ability to act as helper phage with two mutants derived from Fd tet (fKN 16 and fCA 55). Furthermore, we investigate their capability to act as helper phages in SAP selection, where non-infectious helper phage, expressing antibody fragments but not protein 3, can still infect by first reacting with a soluble antigen-protein 3 fusion protein. Gene III mutants were found to be non-infectious, and high titers of infective particles were obtained only when the helper phage was grown in cells harbouring a gene III containing plasmid. An amplification of the phage titer of 10(6) x was achieved in M13-derived phages, when used for the selection of specific antibody fragments. PMID- 7875581 TI - An abundantly secreted glycoprotein from Drosophila melanogaster is related to mammalian secretory proteins produced in rheumatoid tissues and by activated macrophages. AB - An abundantly secreted 47-kDa glycoprotein, DS47, was purified from Drosophila melanogaster (Dm) Schneider line-2 cells, a line exhibiting macrophage-like properties. DS47 is also secreted from several Dm cell lines resembling S2 but not from lines that are morphologically distinct. A cDNA cline was isolated from an S2 cell cDNA library using oligodeoxyribonucleotide probes based on the DS47 amino acid (aa) sequence and found to encode a novel secretory glycoprotein of 452 aa. Analysis of DS47 protein production and mRNA expression during fly development indicates that both are present throughout the entire Dm life cycle, suggesting that DS47 may be important at all developmental stages. In larvae, the DS47 message is made in the fat body and by hemocytes, and secreted into the hemolymph. DS47 is related to a human cartilage glycoprotein, HC gp-39, that is secreted from cell types associated with the arthritic joint, such as synovial cells and activated macrophages. Interestingly, the HC gp-39 message is most readily detected in the human liver, an organ that is somewhat analogous to the Dm fat body. DS47 also shares homology to a mouse secretory glycoprotein, YM-1, identified in activated macrophages. These homologies extend to the chitinase gene family and include a conserved cysteine aa motif, as well as two blocks of aa within the enzymatic active site, although neither DS-47 nor HC gp-39 exhibit chitinase activity. Potential functions of this conserved protein family are discussed. PMID- 7875582 TI - Cloning and characterization of the murine manganous superoxide dismutase encoding gene. AB - The murine manganous superoxide dismutase-encoding gene (MnSOD) is highly homologous in both sequence and organization to its rat homolog. MnSOD is encoded by five exons spanning approx. 7 kb of DNA. RNA blot analysis indicated multiple RNA species, with the major RNA corresponding to a 960-bp message. This major transcript is highly inducible by tumor necrosis factor (TNF) in murine fibroblasts. Analysis of other murine tissues demonstrated ubiquitous expression. RNase protection and primer extension assays used to map the 5' end of the gene revealed a series of closely spaced multiple transcription start points. Sequence analysis of the 1.7 kb of 5' flanking DNA showed high homology to the 5' proximal 950 bp of the rat homolog. Within this region, multiple potential regulatory elements are present, including several SP1 sites, two NF kappa B sites and an antioxidant-response element. However, no TATA box was identified, placing MnSOD in the family of inducible genes that lack consensus TATA-box elements and contain G+C-rich promoter regions. PMID- 7875583 TI - Detection of a functional promoter/enhancer in an intron-less human gene encoding a glutamine synthetase-like enzyme. AB - A human genomic clone, psi GS, containing an intron-less glutamine synthetase (GS)-encoding pseudogene, was isolated by screening a human library. A sequence of 3004 bp, containing the GS coding region and both the 5' and 3' flanking sequences, was identified that exhibits all the characteristics of a processed pseudogene. The coding region shows 93% identity with the human GS cDNA (hGS) sequence and contains two frame-shifts and two termination codons. The coding sequence is flanked by a 9-bp AT repeat and a putative polyadenylation site, AATAAA, at the 3' end. Primer extension analysis and S1 nuclease mapping showed a transcription start point (tsp) 62 bp upstream from the start codon indicating a shorter untranslated region than hGS. Transfection of HeLa cells with cat constructs containing portions of the 5' flanking sequence showed the presence of a functional promoter/enhancer within 200 bp of the tsp, independent of its orientation. PMID- 7875584 TI - A cDNA encoding Arabidopsis thaliana cytoplasmic ribosomal protein L18. AB - A cDNA encoding ribosomal (r) protein L18 of Arabidopsis thaliana (At) was isolated and characterized. The nucleotide sequence contains a 563-bp open reading frame that encodes a 20.9-kDa basic protein. Amino-acid comparison indicated that the predicted L18 r-protein of At has a high degree of homology with L18 of distantly related organisms such as yeast, Xenopus laevis and rat. Genomic DNA analysis suggested that L18 is encoded by a single locus in At. An mRNA of approx. 0.9 kb is detected in all the tissues and developmental stages analyzed. PMID- 7875585 TI - Expression of the Arabidopsis thaliana 2S albumin gene 3 in Saccharomyces cerevisiae. AB - The Arabidopsis thaliana (At) 2S albumin gene 3 (At2S3) has been cloned in YEp13 as a 3.5-kb genomic fragment. To study its expression in Saccharomyces cerevisiae, the accumulation in saturated cultures reached about 0.032% of the yeast total protein, and the product was localized in vacuolar bodies within the cell. The 13-kDa protein was processed to 9- and 4-kDa proteins, as obtained in transgenic tobacco plants. PMID- 7875586 TI - Characterization of a DNA sequence that detects repetitive DNA elements in the Asian rice gall midge (Orseolia oryzae) genome: potential use in DNA fingerprinting of biotypes. AB - We have isolated based on reverse genome hybridization, and sequenced a DNA clone, pNZE25, from a partial genomic library of the Asian rice gall midge Orseolia oryzae (Wood-Mason) (O.o.). Clone pNZE25 is highly A+T rich (67%), lacks any open reading frame and does not display homology to sequences in GenBank. Clone pNZE25 detects a 120-bp repeat in the O.o. genome, as seen from the generation of a 120-bp ladder after Southern analysis of HinfI-digested genomic DNA. When used to probe O.o. genomic DNA digested with DraI, HaeIII or AluI, pNZE25 generates individual specific DNA fingerprints on target DNA isolated from gall midge biotypes collected from different parts of India. PMID- 7875587 TI - Genetic heterogeneity within the coding regions of E2 and NS3 in strains of bovine viral diarrhea virus. AB - We have amplified and sequenced parts of the genomes of eleven laboratory strains of bovine viral diarrhea (BVD) virus originating from North America, New Zealand and Europe. The cumulative nucleotide (nt) sequence heterogeneity of the amplified fragments located in the analysed region of the gene encoding the nonstructural protein NS3 (P80) was 24% as compared to 47% for E2 (Gp53). The nt substitutions in the E2 region resulted in replacements in 42% of amino acid (aa) positions, while the deduced aa sequence of all BVD virus strains remained identical in NS3 and differed from the corresponding region of classical swine fever viruses. This makes possible the differentiation of bovine and porcine pestiviruses. It is suggested that genetic heterogeneity results from passage in transiently infected animals. PMID- 7875588 TI - Mammalian cell/vaccinia virus expression vectors with increased stability of retroviral sequences in Escherichia coli: production of feline immunodeficiency virus envelope protein. AB - Many eukaryotic DNA sequences, especially lenti-retrovirus proviral genomes and their env genes, are unstable when cloned in high-copy-number plasmids in Escherichia coli. Stability can be increased by the use of low-copy-number vectors, although plasmid yields are low. Vectors are described here that contain the intermediate-copy-number P15A ori for cloning, stable propagation and higher yield production of plasmid DNA in E. coli, and the f1 ori for propagation as single-stranded phage. These vectors also have the capacity to direct high-yield production of protein in mammalian cells, and the option of incorporation into and expression via a T7 promoter in vaccinia virus. The SR alpha promoter, encephalomyocarditis (EMC) virus untranslated leader sequence, and poly(A) signal sequence serve as a high-yield mammalian cell expression cassette without the requirement for mRNA capping. A polyhistidine sequence is available at the 3' end of the cassette to facilitate chromatographic purification of protein. neo and gpt genes were included in some vectors to serve as selectable markers, and the dhfr gene was included in one to achieve gene amplification in mammalian cells. Dicistronic mRNAs can be generated by insertion of coding sequences up and downstream from the EMC leader. The utility of these vectors was shown through expression of feline immunodeficiency virus (FIV) Env protein, in conjunction with the tissue plasminogen activator (tPA) leader sequence. PMID- 7875589 TI - Structure of the genes encoding transcription factor IIB and TATA box-binding protein from Drosophila melanogaster. AB - To investigate the structure and regulation of the genes encoding components of the basal RNA polymerase II transcriptional machinery, the Drosophila melanogaster genes encoding transcription factor IIB (TFIIB) and the TATA-box binding protein (TBP) were isolated and characterized. In the TBP gene, a single intron bisects the sequences that encode the two repeated DNA-binding domains of TBP, which supports the notion that TBP evolved from an earlier form that possessed only a single domain. The transcription start points (tsp) were determined, and there was a good correlation between the tsp that were used in vivo and transcription reactions in vitro. The TFIIB and TBP genes have several similar features, which include high A + T content (68 to 74%) upstream from the tsp, multiple copies of an ATTATTATT sequence motif in the proximal promoter region, the absence of a consensus TATA-box element, and small introns (55 to 64 nucleotides). These genes should be useful in the combined genetic and biochemical analysis of TFIIB and TBP in D. melanogaster. PMID- 7875590 TI - Sequences of globin 6 gene alleles and linkage of globin 6 and 7B genes in the insect Chironomus thummi thummi. AB - The purpose of this study was to isolate the stage-specifically expressed Chironomus thummi thummi globin-encoding gene (Gb) 6 (ctt-6). The final product of this gene is hemoglobin (Hb) CTT-VI, a protein that is phylogenetically most closely related to Hb CTT-VIIB. In the absence of chromosomal rearrangement, genes of immediate common ancestry should be closely linked. This was shown for a genomic clone containing the Gb ctt-3 and ctt-4 genes (encoding Hb CTT-III and CTT-IV, respectively), and another clone containing the Gb ctt-2 beta and ctt-9a genes (encoding Hb CTT-II beta and CTT-IXa, respectively). We report the isolation and sequence of two alleles of Gb ctt-6 found on independent genomic clones screened with a ctt-6 cDNA, and the predicted linkage of Gb ctt-6 and a ctt-7B gene. The latter, designated Gb ctt-7B9/5, is unusual in being a chimera of two previously reported Gb ctt-7B genes. The result of a partial gene conversion or an unequal crossover between oppositely oriented genes, the chimeric ctt-7B9/5 represents either an additional ctt-7B locus or a 7B haplotype. PMID- 7875591 TI - Expression of larval-type muscle actin-encoding genes in the ascidian Halocynthia roretzi. AB - Temporal and spatial expression of muscle actin (MA)-encoding genes in the Halocynthia roretzi MA (HrMA) cluster was examined by whole-mount in situ hybridization and Northern blot analyses. Expression of these MA was restricted to larval muscle cells. None of the MA from the cluster was expressed in any adult tissues examined, including two different types of adult muscle tissue, body-wall muscle and heart muscle. When Northern hybridization was performed using an HrMA coding region probe under low-stringency conditions, transcripts were detected in body-wall muscle and heart muscle, but not in other adult tissues. In addition, transcripts of different lengths were detected in body-wall muscle and heart muscle. The comparison of amino-acid sequences among ascidian MA indicates that they possess at least two distinct MA isoforms, found in larval muscle and adult body-wall. These suggest that different MA are expressed in each type of ascidian muscle. PMID- 7875592 TI - Structure and evolution of CyI cytoplasmic actin-encoding genes in the indirect- and direct-developing sea urchins Heliocidaris tuberculata and Heliocidaris erythrogramma. AB - The CyI cytoplasmic actin-encoding genes of Heliocidaris erythrogramma (He), a direct-developing sea urchin, and H. tuberculata, an indirect developer, were isolated and compared to the homologous CyI gene of another indirect developer, Strongylocentrotus purpuratus. Comparisons show that despite the differences in development, the actin gene structures and sequences are highly similar. The coding and 3' untranslated regions are conserved. The 5' He regulatory region has an inserted repeat element, but is otherwise similar to its homologues in the arrangement of presumptive transcription control elements. PMID- 7875594 TI - Two c-myc genes from a tetraploid fish, the common carp (Cyprinus carpio). AB - Two c-myc genes have been isolated from a tetraploid fish, the common carp (Cyprinus carpio). The nucleotide (nt) sequences of the two genes and their flanking regions (CAM1, 8675 bp and CAM2, 5784 bp) have been determined. Both genes contain two coding exons which are homologs of c-myc exons 2 and 3 in higher vertebrates. The nt sequence homologous to c-myc exon 1 of higher vertebrates has not been found. Carp CAM1 and CAM2 presumably encode peptides of 394 and 401 amino acids (aa), respectively. These two peptides share 55-91% aa identity with those of humans, chickens, frog, rainbow trout and zebra fish. The two carp c-Myc have a Glu stretch at the beginning region of exon 3. This Glu stretch is also present in zebra fish, suggesting that it may be characteristic to c-myc genes of cyprinid fishes. The existence of two c-myc in carp is attributed to the tetraploid nature of carp. These two genes share 92.4% nt identity in the coding region and 84.2% in the intron. The two deduced peptides share 94.2% aa identity, suggesting that the tetraploid event probably occurred 58 million years ago. Both of the genes' cDNA clones were obtained from a cDNA library of carp peripheral blood leukocytes, implying that both of the genes are expressed. PMID- 7875593 TI - Analysis of ATF2 gene expression during early Xenopus laevis development. AB - Activating transcription factor 2 (ATF2) is a cellular sequence-specific DNA binding protein that mediates transcriptional activation by the adenovirus (Ad) E1A protein. In injected Xenopus laevis oocytes, E1A-induced transactivation requires an ATF2 recognition sequence within the responding promoters, thereby suggesting that ATF2 is present in oocytes and perhaps has a developmentally important function. As a first step in assessing this, an ATF2 cDNA was cloned and sequenced. The protein encoded by this cDNA contains 486 amino acids and is 92% identical to mammalian ATF2. ATF2 RNA and protein levels are very low in oocytes, but rise dramatically during blastulation. These high levels are maintained through gastrulation, but return to low levels during neurulation. In the blastula, ATF2 RNA and protein are virtually completely confined to cells of the animal pole. The temporal and spatial regulation of ATF2 suggests that it has an important function in early development. PMID- 7875595 TI - Structure and expression of chicken protein kinase PITSLRE-encoding genes. AB - The human PITSLRE protein kinases (PK), members of the p34cdc2 kinase family named according to the single amino acid (aa) code of an important (PSTAIRE) regulatory region [Meyerson et al., EMBO J. 11 (1992) 2909-2917], are candidate tumor suppressor gene(s) localized to human chromosome 1p36.2 and a syntenic region of mouse chromosome 4 [Lahti et al., Nature Genet. 7 (1994) 370-375; Mock et al., Mammal. Genome 5 (1994) 191-192]. At least ten isoforms of this PK family are expressed from three duplicated and tandemly linked genes in humans [Xiang et al., J. Biol. Chem. 269 (1994) 15786-15794]. We have now isolated two different species of PITSLRE PK cDNAs from chicken that encode identical polypeptides, but are clearly expressed from different genes, based on nucleotide (nt) differences. Isolation of one of the corresponding chicken PITSLRE PK genes confirms that only one of the two species of PITSLRE mRNA is expressed from this gene. Comparison of the predicted avian PITSLRE PK aa sequence to human and mouse sequences shows a high degree of sequence identity (> 91%). Like humans, the PITSLRE PK genes in chickens must be closely linked, based on fluorescent in situ hybridization (FISH) localization of these genes to a single chicken microchromosome. PITSLRE PK mRNAs are expressed in two avian B- and T-cell lines. These results suggest that the PITSLRE PK gene family has been well conserved evolutionarily, that the gene duplication observed in humans is not a recent event, and that expression of redundant PITSLRE mRNAs is observed in different vertebrate species. PMID- 7875596 TI - Isolation and sequence analysis of the chicken GABAA receptor alpha 1-subunit gene promoter. AB - A genomic clone containing the 5'-flanking sequence of the chicken GABAA receptor alpha 1-subunit-encoding gene (GabR alpha 1) was isolated and characterized. An intron was found to interrupt the 5'-untranslated region. The transcription start point (tsp) was determined by primer extension, RNase protection and the amplification of chick brain first-strand cDNA. DNA sequence analysis revealed a number of putative transcriptional regulatory motifs, including a TATA box 30 nucleotides upstream from the tsp, and that this region is a CpG island. While there is conservation between the chicken and human GabR alpha 1 sequences, the chicken GabR alpha 1 promoter has a different structure to those reported for the GABAA receptor beta 3- and delta-subunit-encoding genes. PMID- 7875597 TI - Isolation of a mouse cDNA encoding MTJ1, a new murine member of the DnaJ family of proteins. AB - We report the isolation and sequencing of MTJ1, a 1792-bp cDNA from an M27 murine lung carcinoma cell line. The largest ORF within MTJ1 encodes a 63,869-Da protein, containing a 73-amino-acid (aa) sequence (the J domain) that is conserved in proteins of the DnaJ family of chaperonins. The J domain of MTJ1 is bracketed by potential transmembrane domains in a similar configuration to the J domain of the yeast DnaJ-like protein, SEC63. Polyclonal antibodies raised against deduced aa sequences within MTJ1 recognized antigens of 62, 42 and 41 kDa that were enriched in the nuclear and heavy microsome subcellular fractions of murine tumor cells. Northern analysis detected a major 3.2-kb transcript that was present in all murine organs examined, but was relatively underexpressed in brain and heart. PMID- 7875598 TI - Ubiquitous, but variable, expression of two alternatively spliced mRNAs encoding mouse homologues of transcription factors E47 and E12. AB - Two basic helix-loop-helix (bHLH) transcription factors, E47 and E12, are involved in cell-specific gene expression as part of dimeric complexes which interact with the cis-acting motif E-box. Although both generated from a single gene (E2A) by means of alternative splicing, the structural difference in these bHLH regions between the two suggests that the two bHLH proteins may differ in some of their functions. As a step toward elucidating the individual implications of E47 and E12, we investigated the mRNA expression ratios of their homologues (A1 and kA1, respectively) in mouse tissues and cell lines. Both the A1 and kA1 mRNAs were ubiquitously expressed in all tissues examined. However, their ratios varied: e.g., skeletal muscle, 2.2 +/- 0.3 (mean +/- SE); spleen, 2.0 +/- 0.2; pancreatic islet cells, 1.2 +/- 0.2. The A1/kA1 ratios in the cell lines investigated were similar to those of their original tissues. In conclusion, the ubiquity in mRNA expression observed for both the E47 and E12 homologues in mouse provides support for their involvement in a broad range of transcriptional regulation. The variation in the A1/kA1 expression ratios, on the other hand, supports the idea that A1 (E47) and kA1 (E12) each have some unique roles in the functions of these E2A gene-encoded bHLH proteins. PMID- 7875599 TI - The regulatory region and transcription factor required for the expression of rat and salmon pituitary hormone-encoding genes show cell-type and species specificity. AB - The promoter regions of the genes encoding the rat and chum salmon growth hormones (GH) and rat prolactin (PRL) were combined with a reporter gene and introduced into GH- and/or PRL-producing cells from rat. The rat GH and PRL promoters (pGH and pPRL, respectively) were most active in cells producing GH and PRL, respectively. The activity of the salmon pGH was much less than that of the rat pGH in rat GH-producing cells. The regulatory region required for cell-type specific gene expression of pituitary hormones thus contains information, not only for cell-type specificity, but possibly for species specificity as well. A reporter plasmid containing the GH or somatolactin (SL) promoter and an effector plasmid having a gene encoding transcription factor Pit-1 (rat or salmon) were cotransfected into HeLa (human) or EPC (carp) cells. Rat and salmon Pit-1 were more active in HeLa and EPC cells, respectively, indicating that Pit-1 appears to interact species specifically with the transcription machinery. PMID- 7875600 TI - Sequence of the cDNA encoding the Ca(2+)-activated photoprotein obelin from the hydroid polyp Obelia longissima. AB - A cDNA clone encoding the Ca(2+)-activated photoprotein, obelin (Obl), from Obelia longissima was sequenced. The nucleotide (nt) sequence contained two long overlapping open reading frames (ORFs), one of which encoded apoobelin (apoObl). The deduced amino acid (aa) sequence of apoObl revealed that this 195-aa protein has three EF-hand structures that are characteristic for Ca(2+)-binding domains. Strong aa homology was shown among apoObl, apoaequorin and apoclytin. The second ORF present in the obl cDNA consists of 139 codons and encodes a very basic protein with a calculated pI of 10.56 and a molecular mass of 16,153 Da. PMID- 7875601 TI - The zebrafish Zf-Sox 19 protein: a novel member of the Sox family which reveals highly conserved motifs outside of the DNA-binding domain. AB - A cDNA encoding a zebrafish Sox protein (Sry-type high-mobility-group box) was isolated and sequenced. The sequence within the HMG box is close to those of the B subfamily comprising mouse Sox-1, Sox-2, Sox-3 and Sox-14. While much of the rest of the zebrafish protein is unique, there are blocks of amino acids showing considerable identity with regions of Sox-1, -2 and -3. These domains may represent conserved parts of the protein, required for interaction with other proteins, and strengthen the assignment of the zebrafish gene, termed Zf-sox 19, to the B subfamily. PMID- 7875603 TI - Cloning of a mouse adrenocorticotropin receptor-encoding gene. AB - A genomic DNA encoding a mouse adrenocorticotropin (ACTH) receptor was isolated. The predicted 296-amino-acid sequence showed 88.9 and 78.7% identities to the human and bovine homologues, respectively. PMID- 7875602 TI - A murine Thy-1.2 reporter vector containing a SV40 origin for rapid cloning and analysis of eukaryotic promoters. AB - A new vector, pATO, was constructed for rapid cloning and analysis of eukaryotic promoters. When a recombinant pATO, carrying a promoter sequence in its multiple cloning site, was introduced into COS cells, Thy-1.2 protein was produced on the cell surface, and was easily identified by an fluorescein-conjugated anti-Thy-1.2 antibody. The intensity of the fluorescence reflected the strength of the inserted promoter. Since pATO could replicate efficiently in COS cells, the recombinant plasmids recovered from a single COS cell were sufficient to transform Escherichia coli cells. This plasmid is applicable for the rapid and labor saving cloning of promoter elements. PMID- 7875604 TI - Polymorphism of the murine inhibitor of differentiation-controlling gene, Id. AB - The structure of Id was examined by Southern analysis in inbred mouse lines which included five subspecies of Mus musculus. No variation was detected within this species. The species Mus cookii shares the same form found in mice of M. musculus derivation, indicative of a long evolutionary history and a common origin. However, five TaqI polymorphisms were found among several Mus species, suggesting that Id has been modified throughout species diversification. Whether these variants impart functional changes is yet to be determined. PMID- 7875605 TI - Sequence analysis of the rat jun-D gene. AB - A rat jun-D genomic clone was isolated from a rat liver lambda EMBL3 library. Sequence analysis revealed a high sequence similarity with mouse jun-D, and relatively low similarity with human and chicken jun-D. In both the trans activation and DNA-binding domains, however, the amino-acid sequences were well conserved among rat, mouse, human and chicken. PMID- 7875606 TI - Identification of rat alpha-albumin and cDNA cloning of its human ortholog. AB - A rat alpha-albumin mRNA encodes an 80-kDa plasma protein (approx. 20 micrograms/ml in adult rat serum). Its 2-kb human ortholog displays extensive ligand-binding core sequence homology, but striking divergence in the C-terminal domain. PMID- 7875607 TI - The immediate 5'-flanking region of the rat phenylalanine hydroxylase-encoding gene. AB - We have characterized the immediate (465 bp) 5'-flanking region of the rat phenylalanine hydroxylase (PAH)-encoding gene. This sequence shows considerable similarity to the 5'-flanking region of the human PAH gene [Konecki et al., Biochemistry 31 (1992) 8363-8368]. Both sequences lack obvious TATA elements; however, putative regulatory sites, including a potential cyclic AMP-response element and glucocorticoid response elements, are present. PMID- 7875608 TI - The monkey ESP14.6 mRNA, a novel transcript expressed at high levels in the epididymis. AB - A screening strategy designed to identify cloned cDNAs encoding abundant Macaca fascicularis epididymal transcripts has yielded a clone corresponding to a 1.03 kb transcript present at high levels in the epididymis. Following library rescreening, DNA sequence analysis of several near full-length clones predicts a novel, 151-amino-acid protein, epididymal secretory protein 14.6 (ESP14.6), which contains a strong candidate signal peptide characteristic of secretory proteins. PMID- 7875609 TI - A human descendant of the chicken cardiac morphogenic protein ES/130. AB - We report a striking amino-acid sequence similarity between a chicken extracellular matrix protein termed ES/130, involved in early cardiac morphogenesis [Rezaee et al., J. Biol. Chem. 268 (1993) 14404-14411], and a novel human protein termed CG-1, isolated from the glycoprotein fraction of peripheral blood leukocytes [Print et al., Gene 144 (1994) 221-228]. These two proteins may be homologues which have evolved over a period of 270 x 10(6) years. PMID- 7875610 TI - The human serotonin 5-hydroxytryptamine1D receptor pseudogene is transcribed. AB - An examination of mRNA expression of the serotonin genes encoding both psi 5HT1D alpha and the related 5HT1D alpha, demonstrated that the pseudogene is transcribed, and has a tissue distribution similar to the 5HT1D alpha receptor encoding gene. This psi 5HT1D alpha transcript is capable of being translated into a polypeptide of only 28 amino acids in length, and the psi 5HT1D alpha pseudogene most likely arose from a gene duplication or transposition event. PMID- 7875611 TI - The human mdr1 (multidrug-resistance) gene harbours a long homopyrimidine.homopurine sequence next to a cluster of Alu repeated sequences in intron 14. AB - In order to identify specific DNA sequences useful as 'genetic landmarks' in the construction of a complete map of the human mdr1 (multidrug-resistance) gene, we investigated the introns in the central region. In intron 14, we identified a long stretch of a homopyrimidine.homopurine sequence most probably adopting an unconventional DNA conformation, followed by a cluster of three Alu repeated sequences in an inverted orientation. Here, we describe the structure, formation and nucleotide sequence of these DNA elements. PMID- 7875612 TI - An additional 5'-upstream exon exists in the human pleiotrophin-encoding gene. AB - A 2-kb 5' fragment of hPTN (human pleiotrophin-encoding) genomic DNA was sequenced. Within this region we identified a new, upstream exon (U2). Cloning and sequencing of the PCR products of cDNAs from a human melanoma cell line revealed that a 401-bp intron was spliced out between exon U2 and a previously described untranslated exon U1. Our analysis also revealed that previously reported transcription start points (tsp) of PTN are located within exon U1. PMID- 7875613 TI - The role of trauma in postmortem blood alcohol determination. AB - In postmortem cases, a blood sample is frequently obtained by transthoracic (TT) puncture. The purpose of this study was to determine if, in traumatic death, blood samples collected by TT provided a valid sample for blood alcohol analysis. A retrospective study (1980-1986) was conducted to evaluate possible contamination of blood by GI alcohol in traumatic death cases. Out of 6000 cases reviewed, 19 cses with BACs > 500 mg/dl were found and 8 of these cases involved traumatic death with GI laceration and/or transection. The results of this study support the hypothesis that blood samples from the 8 cases had been contaminated, resulting in a falsely elevated BAC. A transthoracic study (1987-1989) was conducted under controlled conditions, where blood alcohol content of TT blood samples was compared with samples collected from the intact heart chamber. Seven out of 28 cases of traumatic injury revealed trauma to the GI tract. The results showed that when GI traumatic injury occurs and unabsorbed ethanol is present in the stomach, contamination of TT blood samples occurs and artificially elevated BACs are obtained. It is recommended that, in cases of traumatic injury, heart blood samples from the intact heart chamber, as well as samples of additional biological fluids, be collected to rule out the possibility of contamination and to ensure that the BAC used for forensic interpretation is accurate. PMID- 7875614 TI - Non-genetic group specific component (GC) observed in a patient with acute non lymphocytic leukemia. AB - This is the case of a male non-lymphocytic leukemia patient who continuously exhibited non-genetic group specific component (GC). The patient was hospitalized 10 months for treatment. The patient's GC type was GC 2-1A2 upon his admission to the hospital, which was consistent with his parents' type. The additional GC protein isoform appeared during treatment and was detected by polyacrylamide gel isoelectric focusing (PAGIEF). This acquired GC component corresponded to GC 1F in PAGIEF and was thought to have originated from GC 1A2 protein. This phenomenon most probably occurred due to a metabolic abnormality or modification of the GC molecule caused by the disease itself, or by chemotherapy. PMID- 7875615 TI - Gunshot suicide with nasal entry. AB - A man with a long history of depression had recently borrowed a rifle. His body was found on its back in bed in his caravan. A rifle lay over the body with the muzzle pointing towards the head. A suicide note was found at the scene. Autopsy revealed entry via the nose with the track passing through the base of the skull to the right parietal region where the main bullet fragments were located beneath the scalp. The history, scene and autopsy findings were consistent with the gunshot wound being suicidal. We can find only one mention of a suicidal gunshot wound with nasal entry in the English-language literature, although a personal communication informed us of a similar case in the Republic of Ireland within the past two years. We report this case because of its unusual nature. PMID- 7875616 TI - Trends in occurrence of drugs of abuse in blood and urine of arrested drivers and drug traffickers in the border region of Aachen. AB - The region of Aachen is located in a triangle on the German, Dutch and Belgian borders and is heavily exposed to drug traffic, due to the differences in national drug policies. The analysis of toxicological casework in the Institute of Forensic Medicine in Aachen was undertaken for the period 1987-1993, i.e. 6 years before and 1 year after the partial suspension of the border control due to the Maastricht Treaty; 2653 cases were registered, among them 988 automobile drivers. The profile of the casework has changed after the opening of the border: up to 1992 most cases were obtained from the customs. In 1993 the prevalence of police samples was noticed. In the population of drivers, blood samples were only taken in 30% of all the cases. In other cases, concerning mainly motorized drug smugglers, only urine samples or seized drugs have been sent for examination. The urine samples in this group were mostly drug-positive. Drug-smuggling drivers appeared to be a risk-generating group for road traffic safety. The analyses of blood and urine samples revealed multiple drug use in most of the cases. Since 1992, a steep increase in the frequency of cocaine-positive blood samples among drivers was noticed. The results of the study indicate that the abolition of the border control affected the road traffic safety in the region of Aachen. PMID- 7875617 TI - A fatal case of buflomedil self-poisoning: toxicological data and literature review. AB - A fatal case of buflomedil (Fonzylane) self-poisoning is presented. Drug identification and quantification in postmortem blood, urine and gastric contents was achieved by means of high pressure liquid chromatography with diode-array detection (HPLC/DAD). Blood concentration was 275 micrograms/ml, > 70 times the usual therapeutic values. Toxicological results are discussed in the light of the existing literature. PMID- 7875618 TI - ABH and Lewis immunohistochemistry of the human eye. AB - ABH and Lewis antigens are detected by immunohistochemistry exclusively in the anterior cornea epithelium and in the conjunctiva bulbi, but not in the ciliary body, in the retina, or in the vitreous body of the eye. The ABH antigens found in the vitreous humor by the absorption elution technique (Rordorf et al., Forensic Sci. Int. 41, 1989, 111-116) are probably glycosphingolipids, which are not detected by immunohistochemistry. They may come from the plasma of uveal blood vessels, or be produced by local cells. PMID- 7875619 TI - Protective effect of peptide leukotriene antagonist on renal failure induced by a tourniquet in rabbits. AB - We studied the effects of a selective antagonist of peptide leukotriene D4/E4 (LY 171883) and 5-lipoxygenase inhibitor diethylcarbamazine (DEC) in renal failure induced by a tourniquet, because peptide leukotrienes (LTs) were suggested to play a key role in our previous study. The hind limbs of anesthetized rabbits were fastened for 5 h and then released for 6 h. LY171883 (4 mg/kg/h) and DEC (40 mg/kg/h) were administered via the aural vein from 30 min before the tourniquet and during the experiment in each tourniquet group. The tourniquet induced renal injuries represented by increases in serum BUN and creatinine, and the injuries in the fastened muscles represented increases in serum CPK and edema index of the fastened site. LY171883 and DEC significantly attenuated the aggravation of the renal functions induced by a tourniquet when compared with the vehicle-treated group. LY171883 did not affect the injuries in the fastened muscles, but DEC attenuated it significantly when compared with the vehicle-treated group. The protection of peptide LT antagonist and 5-lipoxygenase inhibitor in the tourniquet-induced renal failure elucidate that peptide LTs trigger renal failure induced by a tourniquet. PMID- 7875621 TI - The gas (flute) marks on cartridge cases. PMID- 7875620 TI - External appearance of forensic autopsy material of alcoholics. AB - Forensic material of alcoholics was compared with controls with regard to the height, weight, state of nutrition, stature, the ageing process and the presence of traumatic lesions. Surprisingly, it was found that alcoholic women were taller than controls. Alcoholics were significantly more often slightly undernourished, while the extremes, severe obesity or severe undernourishment, did not show any differences. Alcoholics looked older than their age more often than controls. Not unexpectedly, traumatic lesions were more frequent in alcoholics. The lesions were, however, only rarely the result of deliberate violence, but were usually suffered when the alcoholic fell whilst under the influence of alcohol. PMID- 7875622 TI - The inadequacy of death certificates claiming myocardial infarction without autopsy verification. PMID- 7875623 TI - Death due to benzhexol toxicity. AB - A rare case of death due to benzhexol toxicity is reported in a 48-year-old schizophrenic male with a resolving empyema and underlying patchy, mild bronchopneumonia. Toxicological analysis revealed the benzhexol blood and liver concentrations to be 0.12 mg/l and 0.5 mg/kg, respectively. Gastric contents contained 0.4 mg of benzhexol. Other drugs were not detected. It is suggested that for fatalities to occur following benzhexol intoxication, secondary contributory factors, which probably further alter the patient's conscious state, are necessary. PMID- 7875624 TI - [The language and speech skills in 417 children with cleft formations]. AB - Children with cleft palate often suffer from hearing, speech, and language articulation disorders. In order to design an efficient rehabilitation program for children thus affected, it is mandatory to acquire knowledge of the long term results achieved by the various therapeutical strategies including velopharyngoplasty and speech therapy. In this follow-up study 417 children with cleft palate (excluding isolated cleft lip) were examined in an interdisciplinary approach by maxillofacial surgeons, orthodontists, otolaryngologists, audiologists, and speech and language pathologists. The examinations determined that 93% of the children had speech or language disorders and 80% of these children suffered from mild to severe conductive hearing loss with or without clinical signs of otitis media with effusion. In 58 children (14%) with rhinolalia aperta, which had not been improved after one year of speech therapy, velopharyngoplasty with a cranial based pharyngeal flap was performed. The study showed that language skills do not correlate to the type of cleft palate, but rather to the frequency and degree of hearing loss. Using an interdisciplinary approach in early detection and the prompt clinical correction of cleft palate disorders resulted in only 49% of the affected children having to undergo speech and language therapy. In 51% of the affected children no speech therapy was necessary at all. The results presented in this study lead to the conclusion that our program for managing the rehabilitation of children with cleft palate is efficient. PMID- 7875625 TI - [Incisor roots in the mandibular symphysis in the computed tomogram and in the lateral teleradiogram]. AB - On the basis of lateral cephalograms and computer tomograms (CT) the position of the incisor roots and the bone structure surrounding them were studied. Nine patients each had an axial CT of the mandibular symphysis area and, in addition, 6 of these patients had lateral cephalograms. In order to compare both images, we defined a classification scheme as follows: Class 1 = the incisor roots are projected into the midst of the oral corticalis of the symphysis; class 2 = the roots are in contact with the oral corticalis; class 3 = the incisor roots are at a distance to the oral corticalis. The results from the 2 types of visualization were then compared. When looking at the bone structures surrounding the incisor roots, the lateral cephalograms failed to yield an exact differentiation. Such details can be best examined in the axial CT layers, because in the lateral cephalogram the 4 incisor roots are over projected to 1 root. The space for movement of the incisors is narrow. The root of each and every patient showed a different position in oro-buccal direction. This fact must be taken into consideration in clinical practice, especially when employing fixed appliances with 3-dimensional root control. PMID- 7875626 TI - [The mobility of the anterior teeth after the direct bonding of lingual retainers. A comparison of in-vitro and in-vivo measurements]. AB - Lingual retainers are today widely used in the long-term stabilization of incisors. In that they are left in place for a period of years, the question arises to what extent lingual retainers allow sufficient physiological movement. To answer this question first an in-vitro study of the inflexibility of various retainers under horizontal and vertical load was carried out. Next the retainer which limited physiological movement to the least degree was studied in-vivo. Both dynamic and static mobility measurements of the lower jaw front teeth were carried out on 5 patients before and after bonding the retainers. A self developed measuring instrument was used to make the static measurements and a periotest device was employed in the dynamic measurements. The in-vitro tests indicated that, with the exception of the retainer made of multistranded 0.0155" wire or glass fiber, a significant reduction in tooth mobility can be expected with all the retainers. However, the static in-vivo measurement carried out with the 0.0155" wire resulted in a distinct reduction in tooth movement. The dynamic measurements using the periotest device confirmed this finding. With regard to clinical practice within the framework of long-term retention, highly flexible retainers appear to be the most suitable and are to be recommended. PMID- 7875627 TI - [The force level of pseudoelastic leveling wires in relation to interbracket distance]. AB - One of the arguments for the introduction of pseudo-elastic wire materials was "the way they work biologically", that is to say, on the one hand small and uniform force over an extended period of time and on the other the avoidance of excessive forces during the leveling phase. Since an evaluation of the operative force of such an arch wire is dependent on temperature, stress-strain curve, and method of activation, and because the extent of the activation is no longer directly proportional to the operative force, the result is that it is often difficult to determine clinically, whether a safe maximum force is not being exceeded. To clarify this issue arch wires were tested in a three bracket test simulating to the greatest degree possible a clinical situation. The inter bracket distance was selected in accordance with the situation in the upper and lower incisor region independent of the width of the bracket. The results showed rather high forces for some of the wires. Often these forces were higher in the mandibular situation due to non-ideal force deflection curves than in the supramaxilla. One of the tested materials did, however, effectively limit the operative force in the upper and lower jaw. Especially significant is that the differing characteristics of the tested wire materials result in a completely different action in relation to force development. PMID- 7875628 TI - [Neon-colored plastics for orthodontic appliances. Biocompatibility studies]. AB - Public concern and issues of liability have made product safety a major concern throughout the medical field including orthodontics. The purpose of this study was to test the biocompatibility of the new neon colored plastic materials to be used for removable orthodontic appliances before they reach the market and are used in patient treatment. In addition, eight modifications of this synthetic material, which has been used in appliances for many years, were examined without neon color. The procedures established tested for: 1. mutagenicity, 2. toxicity, and 3. irritation of the mucous membrane. As alternatives to using animals the Ames Test, the Agar Overlay Assay, and the HET-CAM Test were employed to test for these properties. The tests revealed that, when the manufacturer's instructions are followed, neither the polymerized materials as used in patient appliances nor the shavings resulting from the orthodontist or the technician grinding the appliance exhibit mutagenic, toxic, or irritating properties. PMID- 7875629 TI - [The shearing strength of titanium brackets depending on the coating procedure]. AB - It has long been recognized that corrosion of the metal alloys used in the different fields of dentistry can cause intra-oral problems such as allergic reactions. Titanium, a metal all but impervious to corrosion, presents an alternative to the metal alloys used in the fabrication of orthodontic brackets. The purpose of this study was to test the bonding strength between titanium brackets treated with 5 different opaque and non-opaque coatings and a 2-phase adhesive. Five coating methods were tested: N1 (Dentaurum), N2 (Dentaurum), Rocatec (Espe), Sebond (Schutze), Silicoater Standard (Kulzer). After bonding the brackets with a mix adhesive, they were thermocycled and then the shear bonding strength established. Silicoated titanium bracket bases showed clinically acceptable bonding values with the exception of those coated with Sebond without opaquer layer. While the silicoating methods N1, N2, and Rocatec demonstrated minimum bonding strength using the opaquer Visio-Gem, the bonding strength of the bracket bases coated with Sebond MKV, Silicoater Standard and the opaquer appropriate to each was significant increased. Among all the coated surfaces, methods N1, N2, and Rocatec appear to establish the optimum bonding strength values. In addition, the thin opaquer layer (Visio-Gem) used together with these methods offers a good surface adaptation of the bracket to the tooth surface. PMID- 7875630 TI - [The radiological-histological interpretation of artificial bone defects of the basal maxillary sinus cortical bone]. AB - Twenty-one lateral maxilla specimens were taken from human autopsy specimens and after removing soft tissue 40 differing tooth roots of 23 molars and premolars were ground to create large artificial bone defects in the supporting cortical bone of the basal maxillary sinus. Conventional dental radiographs and axial CT scans were then compared with the macroscopic findings in relation to the identification of the artificial bone defects. Next the jaw segments were dissected analogous to the axial CT scan and corresponding histological microsections were prepared for a radiological-histological comparison. None of the artificial bone defects were identifiable on the dental radiographs. In comparison to this, however, cortical bone defects were identifiable on 25 tooth roots (62.5%) on the CT scans. The lateral demarcation of the antral defects on the CT scans depends on the setting of the tooth root, on the adjacent bone morphology, and on the visualization of the periodontal ligament space. If the periodontal space shows up on the CT images, it becomes possible to demarcate of a thin, 0.2 to 0.5 mm, cortical bone layer of the basal maxillary sinus. PMID- 7875631 TI - [The influence of information and communication in the orthodontic consultation and treatment visit. II. The communication style and compliance]. AB - The establishment of a good rapport between dentist and patient is together with providing information a basic prerequisite for successfully motivating the patient to comply with the guidance the dentist provides. Both the style adopted in verbally communicating with the patient and also nonverbal communication play a decisive role in the establishment and maintenance of such a relationship. In the pilot study presented here, which draws on psychological interaction analysis of video recordings taken of the initial consultation with 27 patients and of 28 routine treatment sessions with different patients, the typical interaction patterns between the orthodontist and the patient are objectively assessed and compared. The most important findings of the study were: (1) The mean duration of the chairside sessions was lowest during routine encounters with cooperative patients. (2) During consultations approximately 2/3 of the time was taken up talking to each other. On the other hand, in treatment sessions with uncooperative patients only 1/4 of the time was devoted to verbal communication. (3) The orthodontist dominated the conversation in all groups and especially in conversing with the uncooperative patients. (4) In the consultation sessions the dentist and the patient related relatively strongly to each other. (5) Providing mere information significantly predominated over any discussion of the professional aspects of the treatment. (6) During the consultations eye contact was maintained over almost all of the sessions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875632 TI - Classification and mechanism of action of antiarrhythmic drugs. AB - The present paper reviews classification and mode of action of agents that suppress extrasystoles and tachyarrhythmias. These are classified according to their electrophysiological effects observed in isolated cardiac tissues in vitro (Vaughan Williams, 1989). Fast sodium channel blockers (class I) which reduce the upstroke velocity of the action potential are usually subclassified into three groups, class I A-C, according to their effect on the action potential duration. Beta-adrenergic antagonists (class II) exert their effects by antagonizing the electrophysiological effects of beta-adrenergic catecholamines. Class III antiarrhythmic agents (eg amiodarone) prolong the action potential and slow calcium channel blockers (class IV) suppress the calcium inward current and calcium-dependent action potentials. The classification of antiarrhythmic drugs is still under debate. This particularly applies to agents of class I and III. The effect of class I agents is frequency-dependent because the binding affinity of these drugs to the sodium channel is modulated by the state of the channel (modulated receptor hypothesis). Class I agents bind to the channel in the activated and inactivated state and dissociate from the channel in the rested state. This occurs at a drug-specific rate so that class I agents can be subclassified into only two groups, namely in those of the slow- and fast recovery type respectively (time constant of reactivation greater or smaller than 1 s). Slow-recovery class I agents affect regular action potentials at normal heart rates which can more easily lead to a lengthening of the QRS duration in the ECG, to conduction disturbances and hence to pro-arrhythmic effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875633 TI - In vitro electrophysiological detection of iatrogenic arrhythmogenicity. AB - Cardiac arrhythmias and sudden death have been associated with both therapeutic and toxic doses of a number of cardiotropic and non-cardiac drugs. Generally the drug-induced electrocardiographic (ECG) alterations have been well described, whereas corresponding cellular electrophysiological effects are poorly documented or lacking. Taking into account the recent advances in the understanding of the mechanisms underlying arrhythmias and antiarrhythmic effects, suitable relationships can be established between ECG alterations and drug effects on cardiac action potential. Thus, a decrease in maximal upstroke velocity (Vmax) and membrane depolarisation leading to cellular inexcitability may slow conduction, prolong QRS interval duration and result in incessant wide QRS ventricular tachycardia. On the other hand, lengthening of the repolarisation phase and early afterdepolarisations (EADs) have been proposed as a mechanism for prolonged QT interval and subsequent Torsades de Pointes. A representative study aimed at detecting the arrthymogenic potentiality of a drug is given, by examining carefully the concentration- and frequency-dependent effects of four neuroleptics (sultopride, droperidol, thioridazine and clozapine) on Purkinje fibers and comparing them with the reported iatrogenic arrhythmias. The results showed that 10 to 100 microM sultopride and 0.01 to 1 microM droperidol exerted "pure" class III effects. In addition, higher concentrations (3 to 30 microM) of droperidol reversed the prolonging effect on repolarisation concomitantly with a dose- and frequency-dependent decrease in Vmax, action potential amplitude and resting membrane potential (class I effects) resulting in cellular inexcitability at 30 microM. Similar class I effects were induced by thioridazine and clozapine concomitantly with a slight prolonging effect on final repolarisation (class Ia effects). In the presence of sultopride (30 and 100 microM) and droperidol (0.3 to 3 microM), EADs developed at plateau level. Their incidence, amplitude and number were influenced by extracellular K or Mg concentration, stimulation frequency, modification of Ca entry (by nifedipine or isoproterenol). These experimental results fit well with clinical data although they need further development to precise underlying ionic mechanisms. Therefore, in vitro studies should be considered before clinical prospects for future drug development. PMID- 7875634 TI - Influence of ischaemia and reperfusion on cardiac signal transduction. G protein content, adenylyl cyclase activity, cyclic AMP content, and forskolin and dibutyryl cyclic AMP-induced inotropy in the rat Langendorff heart. AB - We investigated whether post-receptor alterations contribute to the diminished beta-adrenergic inotropic effects in the rat Langendorff heart following ischaemia (I) and reperfusion (R). We quantitated immunodetectable Gs and Gi protein alpha-subunit content, basal and stimulated adenylyl cyclase activity and cyclic AMP (cAMP) content in normoxic, ischaemic (30 min) and ischaemic reperfused (30 min) hearts. In addition, we measured the inotropic response of normoxic and reperfused Langendorff hearts to forskolin and dibutyryl cAMP (db cAMP). Immunodetectable Gs and Gi alpha-subunits were unaltered by I or R. Basal adenylyl cyclase activity was decreased during I, but recovered during R. In membranes from normoxic hearts, isoprenaline, GTP, Gpp(NH)p, NaF, forskolin or Mn2+ enhanced adenylyl cyclase activity. This increase in activity was diminished in ischaemic hearts, but could be restored by R. cAMP content decreased time dependently during I and did not recover by R, indicating ATP depletion. Forskolin and db-cAMP induced an inotropic response in normoxic hearts, which was virtually abolished after I and R. We conclude that adenylyl cyclase responsiveness is impaired during I. Since adenylyl cyclase responsiveness recovers during R, whereas inotropic responses to forskolin and db-cAMP are virtually absent in reperfused hearts, an additional mechanism downstream of cAMP formation appears to be defective during R, which prevents recovery of inotropic responses to hormonal stimulation. PMID- 7875635 TI - Effects of salbutamol and BRL 37344 on diastolic arterial blood pressure, plasma glucose and plasma lactate in rabbits. AB - The aim of this study was to investigate in rabbits the diastolic arterial blood pressure, plasma glucose and plasma lactate responses to salbutamol (a selective beta-2 adrenoceptor agonist) and BRL 37344 (a selective beta-3 adrenoceptor agonist) in comparison with CGP 12177 (a potent beta-1 and beta-2 adrenoceptor antagonist which also acts as a partial beta-3 agonist), isoprenaline (a non selective beta-1, beta-2 and beta-3 adrenoceptor agonist) and adrenaline (a non selective beta and alpha adrenoceptor agonist). All drugs were iv infused at the same dose: 0.3 microgram/kg/min (30 min). In sodium pentobarbitone (40 mg/kg) anasthetized animals none of these compounds altered diastolic arterial blood pressure. BRL 37344 (0.1, 0.3, 1 microgram/kg/min) did not modify this parameter either. In conscious 24-h fasted rabbits, only adrenaline was able to increase plasma glucose levels. By contrast, under the same experimental conditions, salbutamol, isoprenaline and adrenaline, but not BRL 37344 or CGP 12177, induced a significant increase in plasma lactate levels. Finally, the salbutamol-mediated plasma lactate response was inhibited in the presence of clonidine (2 micrograms/kg/min, an alpha-2 adrenoceptor agonist), a drug considered to have opposite effects (stimulatory and inhibitory) on the adenylate cyclase system. In conclusion, these data suggest that only beta-2 adrenoceptor stimulation is able to increase plasma lactate levels, a response which is inhibited by alpha-2 adrenoceptor stimulation. PMID- 7875636 TI - Inhibition of Na/Ca exchange stimulates insulin release from isolated rat pancreatic islets. AB - Na/Ca exchange was recently shown to regulate cytosolic free Ca2+ concentration ([Ca2+]i) in the pancreatic B-cell. The aim of the present study was to provide direct evidence that inhibition of the activity of the exchange may also increase insulin release. In the presence of extracellular Na+, caffeine stimulated 45Ca outflow but did not increase insulin release from islets perifused in the presence of 2.8 mM glucose. By contrast, in the absence of extracellular Na+, caffeine almost failed to increase 45Ca outflow and reversibly stimulated insulin release despite the fact that the absence of extracellular Na+ per se reduced basal insulin release. Similar findings were observed in islets perifused at a higher glucose concentration (8.3 mM) except that, in the presence of extracellular Na+, caffeine more markedly increased 45Ca outflow and stimulated insulin release. Our data provide direct evidence that inhibition of Na/Ca exchange with resulting blockade of Ca2+ outflow may increase insulin release from the pancreatic B-cell under suitable experimental conditions. PMID- 7875637 TI - Comparative pharmacokinetics of two diastereoisomers dexamethasone and betamethasone in plasma and cerebrospinal fluid in rabbits. AB - The two diastereoisomers dexamethasone (DXM) and betamethasone (BTM) were infused at two different doses (2, 10 mg.kg-1) in anesthetized rabbits. Samples of plasma and cerebrospinal fluid were collected over a 180-min period. Steroid concentrations were measured by high performance liquid chromatography. The terminal half life (85.7 +/- 20.8 min and 102.2 +/- 29.6 min for DXM; 117.6 +/- 19.8 min and 118.5 +/- 15.8 min for BTM) and the mean residence time (121.4 +/- 27.7 min and 146.1 +/- 41.3 min for DXM; 168.6 +/- 28.1 min and 172.2 +/- 20.6 min for BTM) were unchanged between the doses. Dose-dependent changes in the area under the curve normalized by the dose, then volume distribution and clearance were observed. The average percentage of DXM and BTM bound to plasma proteins were 78.1 +/- 11.5% and 88.3 +/- 5.1% respectively at the lower dose, and decreased significantly with 10 mg.kg-1. DXM appeared more rapidly in the CSF, the highest concentrations of DXM were obtained within 15 min after the end of the injection. The CSF levels were lower than that of plasma unbound and the passage through the blood-brain barrier was saturable. These results will complicate pharmacokinetic and pharmacodynamic analysis. PMID- 7875638 TI - Pharmacokinetic-pharmacodynamic modeling between pinacidil or pinacidil-N-oxide plasma levels and systemic and regional hemodynamic effects in healthy volunteers. AB - Pinacidil (P) lowers blood pressure through peripheral vasodilation, but also induces dose-dependent side-effects. In a previous placebo-controlled, randomized, double-blind and crossover study, performed in six healthy male volunteers, we investigated the systemic and regional hemodynamic effects of a single oral administration of 25 mg of P (sustained-release form) and measured the plasma concentrations of P and of its active metabolite, pinacidil-N-oxide (PO). In the present study, our goal has been to investigate the relationships between P and/or PO plasma concentrations and P administration effects on systolic, diastolic and mean arterial pressures (SAP, DAP, MAP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), brachial and carotid arteries' diameters (BAD, CAD), flows (BAF, CAF) and vascular resistances (BVR, CVR) which were assessed before and at different time intervals after drug intake. Concentration-effect relationships were investigated using both linear and log-linear multiple regression models with P, PO or both P and PO as independent variables (six models). Significant linear relationships were observed between P and/or PO and SAP, DAP, MAP, TPR, BAD, BAF, BVR, CAD and CVR. For example, TPR (dynes.s/cm5) = 1308-3.031 x P (ng/ml), R = 0.57, P = 0.0037; BVR (mmHg.s/ml) = 58-0.261 x P (ng/ml), R = 0.56, P = 0.0042. Almost similar R values were obtained using P, PO, or both P and PO. The use of log-linear models did not improve the fittings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875639 TI - Effects of dipyridamole, soluflazine and related molecules on adenosine uptake and metabolism by isolated human red blood cells. AB - The suggestion that adenosine may have beneficial effects on post reperfusion survival following cardiac ischaemia has led to the search for agents which increase the concentration of this substance in the ischemic region as a possible therapeutic approach to the treatment of angina and myocardial infarction. In the present study, dipyridamole, soluflazine and lidoflazine, known inhibitors of the nucleotide exchange system, have been shown using an HPLC method to prevent the decrease in the concentration od added adenosine outside human red blood cells in vitro. However, the results suggest that this effect was due to inhibition of adenosine deaminase rather than inhibition of nucleotide exchange as had previously been suggested. The selective inhibitor of adenosine deaminase erythro 9-(2-hydroxy-3-nonyl adenosine) exhibited the same profile of activity in the human red blood cell assay. pIC50 values for the four compounds named above were found to be 6.80 +/- 0.09, 6.95 +/- .03, 6.10 +/- 0.14 and 7.39 +/- 0.05 vs adenosine disapearance observed in the extracellular incubation medium respectively. Thus, as the disappearance of adenosine outside the cells was not due to its uptake but to its catabolism, this in vitro method does not appear to be predictive for the ability of compounds to act on adenosine uptake into cardiac myocytes. Any antiischemic action of these agents is more readily explained by an inhibition of the catabolism of adenosine and not by the inhibition of its transport across the membrane of cardiac myocytes. PMID- 7875640 TI - Influence of food and body weight on the pharmacokinetics of penticainide. AB - The pharmacokinetics of penticainide, a class Ic antiarrhythmic drug, was studied in 16 healthy adults (eight males and eight females) after a single 300-mg oral dose in fasting conditions and with a standard meal. Penticainide concentrations in plasma and urine were measured by hplc. The pharmacokinetic parameters of penticainide including Cmax, tmax, AUC and t1/2 were not significantly altered in the presence of food. AUC values (mean +/- sd) were 50.68 +/- 10.8 mg.h.l-1 and 49.52 +/- 9.87 mg.h.l-1 in the absence and presence of food, respectively. However, a significant difference was observed between males and females in both fasting and fed conditions with a higher value of the apparent oral clearance in the second group. The values of apparent oral clearance, expressed in weight normalized units were 1.33 +/- 0.35 ml.mn-1.kg-1 (male) and 1.93 +/- 0.34 ml.mn 1.kg-1 (female) in fast conditions (P < 0.01) and 1.38 +/- 0.28 ml.mn-1.kg-1 (male) and 1.93 +/- 0.49 ml.mn-1.kg-1 (female) in fed conditions (P < 0.02), respectively. The pharmacokinetics of penticainide is not modified by the presence of food, but an influence of body weight may be considered. PMID- 7875641 TI - Pharmacokinetics of cyclophosphamide in patients with systemic necrotizing angiitis. AB - Cyclophosphamide pharmacokinetics were investigated following administration to patients with systemic necrotizing angiitis. Ten patients (eight women and two men) received cyclophosphamide as a 1-h-rate-constant intravenous infusion at doses ranging from 600 to 1200 mg. All patients received concomitant oral prednisone (1 mg/kg/d). Blood samples were collected at the end of drug infusion and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h later. Serum cyclophosphamide concentrations were assayed by high pressure liquid chromatography. The peak serum cyclophosphamide levels ranged from 15.7 to 29.4 mg/L. The mean cyclophosphamide elimination half-life was 6.2 +/- 1.3 h (mean +/- SD). The mean apparent volume of distribution and mean total plasma clearance were, respectively, 0.75 +/- 0.22 L/kg (mean +/- SD) and 83 +/- 22 mL/min (mean +/- SD). These results obtained in systemic vasculitic diseases were consistent with those observed in other studies with cancer patients receiving comparable doses of cyclophosphamide. PMID- 7875642 TI - Influence of hepatic impairment on the pharmacokinetics of nefazodone and two of its metabolites after single and multiple oral doses. AB - The pharmacokinetics of nefazodone, a new antidepressant, and two of its active metabolites, hydroxy-nefazodone and m-chlorophenylpiperazine, were determined after single and repeated oral escalating doses of 50, 100 and 200 mg, in healthy volunteers (n = 13) and patients with mild (n = 13) or severe (n = 6) hepatic impairment. All subjects were classified according to their dextromethorphan oxidation capacity. In healthy volunteers, nefazodone was rapidly absorbed after which the plasma concentrations declined with an apparent elimination half-life ranging from 2.7 +/- 1.7 h to 10.2 +/- 4.4 h according to the dosage. Hydroxy nefazodone appeared rapidly in plasma and its time-course (half-life ranging 1.4 +/- 0.9 h to 6.5 +/- 1.6 h) paralleled that of nefazodone, while mCPP showed low and variable concentrations. The disproportionately longer half-life and more markedly increased Cmax and AUC0-48 which was observed with dosage and treatment duration, and moreover AUC0-12 at steady state significantly higher (P < 0.05) than AUC0-infinity after single dose demonstrated the non-linearity of the pharmacokinetics of nefazodone and hydroxy-nefazodone. The constant molar AUC0-48 hydroxy-nefazodone/nefazodone ratio (0.32 +/- 0.04) and the close correlation (r2 = 0.95) between kinetic parameters of nefazodone and hydroxy-nefazodone suggest that nefazodone hydroxylation is not a saturable process. The kinetics of nefazodone and metabolites were significantly affected by severe but not by mild liver insufficiency. As a consequence, on a pharmacokinetic basis nefazodone should be used with caution in severely hepatic impaired patients. PMID- 7875643 TI - Effect of muscular exercise by bicycle ergometer on erythrocyte purine nucleotides. AB - The effect of muscular exercise by bicycle ergometer on erythrocyte purine nucleotides was investigated in 6 athletes. Muscular exercise increased the concentration of inosine monophosphate from 5.9 +/- 1.1 to 7.3 +/- 1.3 nmol/ml in venous erythrocytes and from 5.7 +/- 1.0 to 6.8 +/- 1.4 nmol/ml in arterial erythrocytes, respectively, while it decreased the concentrations of adenosine diphosphate and adenosine monophosphate from 189.3 +/- 42.7 to 141.2 +/- 26.9 and from 26.0 +/- 7.8 to 15.7 +/- 4.3 nmol/ml in venous erythrocytes and also decreased their concentrations from 195.1 +/- 51.0 to 141 +/- 29.2 and from 26.5 +/- 9.6 to 14.8 +/- 3.0 nmol/ml in arterial erythrocytes, respectively. The muscular exercise also increased the concentration of inorganic phosphate in venous plasma from 1.12 +/- 0.12 to 1.46 +/- 0.22 mmol/l, that of NH3 in blood from 41.90 +/- 6.91 to 150.22 +/- 50.80 mumol/l, that of lactic acid in blood from 7.90 +/- 1.71 to 61.03 +/- 18.43 mg/dl and that of hypoxanthine in venous plasma from 1.32 +/- 0.36 to 18.14 +/- 4.87 mumol/l, respectively. Therefore, in vitro study was performed to investigate whether inorganic phosphate, NH4Cl, lactic acid or hypoxanthine affects nucleotides in erythrocytes. After 2 hour incubation, 2 mM inorganic phosphate increased the erythrocyte concentration of inosine monophosphate 1.6 fold but decreased the erythrocyte concentrations of adenosine monophosphate and adenosine diphosphate 0.72 and 0.89 fold, respectively, in the suspension (pH 7.35), as compared with 1 mM inorganic phosphate. However NH4Cl, lactic acid or hypoxanthine did not affect erythrocyte purine nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875644 TI - the "Ulm Zucker Uhr System" and its consequences. AB - The "Ulm Zucker Uhr System" comprises a microdialysis probe, a biosensor (Glucosensor Unitec Ulm s.c.), a sender transferring telemetrically the glucose concentrations, and a receiving indicator. The "Zucker Uhr" or "Sugar Watch" looks and operates like a normal wrist watch. We now present the functioning pre prototype of the first portable system, which 1) is continuously measuring in s.c. tissue the Tissue Glucose (T.G.) concentration in the intercellular fluid on line enzymatically by combining an enzymatic and an electrochemical (amperometric) technique. 2) is transferring in the patient via the "Zucker Uhr" once per minute the actual tissue glucose concentration, i.e. 1,440 values/24 hours or even 2880 values/48 hours, 3) is actually alarming the patient by optical and acoustic means, when the tissue glucose is too high (hyperglycemia) or too low (hypoglycemia), 4) is storing digitally all values and, therefore, permitting the dialogue between doctor and patient as to his diabetes control in view of his 24 h glucose profile, which is visual on a computer screen. The advantage for the patient is on the one hand the elimination of the multiple pricking in the finger tips for providing capillary blood, and on the other hand, permitting the preview of the limitation and perhaps the complete elimination of the microangiopathy of the retina, kidneys and nervous system. The trend of the T.G. decreases is readily recognizable, which indicates immediately the dangerous hypoglycemia. Likewise, over 48 hours, the hyperglycemic periods are transmitted and recorded which are not measured and reflected by the HbA1 and HbA1c conventional measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875645 TI - Clinical usefulness of the glucose concentration in the subcutaneous tissue- properties and pitfalls of electrochemical biosensors. AB - Biosensors are miniaturized analytical tools which comprise a biological detection element providing specificity to the analyte, and a physical transducer which guarantees an output signal, e.g. an electric current the size of which is proportional to the concentration of the analyte. They provide the unique possibility of continuous in vivo monitoring. Glucosensors were in fact the first biosensors under study. Among them, the most advanced devices are measuring amperometrically the hydrogen peroxide generated in a stoichiometric relation to the prevailing glucose concentration during glucose oxidase-mediated glucose oxidation. They proved useful in commercially available glucose analyzers and in experimental subcutaneous monitoring. Here it is shown (a) that under steady state conditions the s.c. glucose concentration is nearly identical to that in blood, (b) that s.c. inserted glucose electrodes do mirror the intracorporal glucose concentration both under hypo-, normo-, and hyperglycaemic conditions with a clinically relevant accuracy, (c) that even stable feedback control of intracorporal glucose concentration is possible employing s.c. glucosensor signal as an input to automated insulin pump controller, and (d) that stable function of s.c. sensor is usually accomplished over intervals up to one day but in some cases applications over up to ten days could be realized. The underlying problem consists in an insufficient functional biostability which is a function of biocompatibility and size of the sensor, of its sterility, and of the permanent skin penetration. The latter is still required to get the device in place, to keep it in function, and to make use of the data under any condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875646 TI - Calibration problems of subcutaneous glucosensors when applied "in-situ" in man. AB - Continuous glucose monitoring is the conditio sine qua non to achieve total automation in glucose-controlled insulin-delivery. Several types of glucosensors have been designed according to the enzyme-amperometric method to measure the glucose in different human compartments. However, problems such as long-term stability and calibration prevent this technique being put into practice. A feasible method is needed to calibrate the glucosensor and at the same time should be accepted by the patients. To achieve calibration we determined the absolute tissue glucose, as well as the microdialysis recovery in-vivo, in healthy subjects under normal conditions and during a hyperglycaemic clamp by applying a device based on the recirculation of phosphate buffer saline in a microdialysis probe implanted in the s.c. adipose tissue. The first experiments carried out were promising and encouraging, but further investigations are still needed to favour an ideal "before implantation, all in-vitro" method to calibrate a s.c. glucosensor. PMID- 7875647 TI - Implantable electrocatalytic glucose sensor. AB - An electrocatalytic glucose sensor for in vivo application has been developed to determine the glucose level in blood and further to control the insulin dosage in a closed loop system for diabetes therapy. The principle of the electrocatalytic glucose sensor is based on the direct electrochemical oxidation of glucose at a membrane-covered platinum electrode. For a possible clinical application the sensor was built as a catheter. A set of implantations in the vena cava of sheep demonstrated the potential feasibility of the sensor. The sensor values were simultaneously checked by the enzymatic analysis of glucose in blood samples drawn separately from a femoral vein. It was possible to determine the glucose concentration in sheep for more than 130 days with tolerable deviations from glucose reference measurements. The mean error was 2.5 mmol/l. One of the catheters was explanted after 211 days and the histological examination revealed a good biocompatibility of all materials used. In additional experiments, the differences of the glucose concentration in vena cava as well as in the anterior and posterior femoral veins of a sheep were examined during glucose tolerance tests. These experiments verified our method of in vivo calibration of the long term implantable glucose sensor. PMID- 7875648 TI - Glucose sensor in containment technology. AB - A new transducer concept for miniaturized immobilized enzyme glucose sensors is presented. The enzyme containing membrane is anchored inside the microcontainment of a silicon chip together with the metal electrode. Containment based sensors are ideally suited for integration into microsystems. The fabrication process is planned as a full wafer process allowing transfer to low-cost mass-production with a narrow variability. The functionality of the containment concept is demonstrated by the fabrication of chips with single GOD-based amperometric glucose sensors which have been tested in glucose solution. The advantages of the containment technology are discussed. PMID- 7875649 TI - Implantation of non-toxic materials from glucose sensors: evidence for specific antibodies detected by ELISA. AB - After subcutaneous implantation of glucose sensors into LEW.1A rats, antibodies could be detected by means of enzyme-linked immunosorbent assay against the outer membrane (cellulose acetate) but not against either the inner membrane (polyethylene) or glucose oxidase (GOD). The kinetics of humoral immune response were investigated implanting different polymeric membranes such as polyurethane, cellulose acetate, regenerated cellulose. The highest antibody titer was detected against regenerated cellulose. There was no cytotoxic effect in vitro by any of the tested materials as examined on monolayer cultures of the mouse fibroblast cell line L-929. Thus immunogenicity is suggested to be considered as a parameter in biocompatibility testing of implantable medical devices. PMID- 7875650 TI - Combination of microdialysis and glucose sensor for continuous on line measurement of the subcutaneous glucose concentration: theory and practical application. AB - The microdialysis technique can be used to get dialysates of the subcutaneous tissue, which can be continuously measured by an amperometric glucose sensor. In order to get further insight into the microdialysis procedure, we used a steady state theory for microdialysis to predict the recovery of glucose in the dialysate and compared the results to experimental data obtained by a combination of the microdialysis technique with continuous amperometric glucose sensing. The recovery of glucose obtained in vitro for two different microdialysis probes was close to the theoretical predictions. When quantifying the predictions of the model with regard to the spatial concentration profile in the subcutaneous tissue, it appeared, that the presence of the microdialysis probe depressed the concentration of glucose for 0.2 mm from the probe surface. In a 24 hour in vivo experiment, there were less fluctuations in the sensor signal when the patient was lying in bed compared to the time, when the patient could move freely. In conclusion, the combination of microdialysis and glucose sensor seems to be a promising approach to a continuously functioning glucose sensing system. However, the microdialysis procedure itself disturbs the surrounding of the probe leading to a concentration gradient of glucose. This might explain some differences between the course of blood glucose and the course of subcutaneous glucose, measured by the combination of microdialysis and an amperometric glucose sensor. Further developments of such systems should aim at implanting microdialysis devices which have a minimal influence upon the tissue metabolism. PMID- 7875651 TI - Cellular Ca2+ ATPase activity in diabetes mellitus. AB - Basal and maximal Ca2+ ATPase activity was studied in erythrocytes of 29 healthy controls, 15 patients with insulin-dependent diabetes mellitus (IDDM) and 22 patients with non-insulin-dependent diabetes mellitus (NIDDM). Basal and maximal Ca2+ ATPase activity was significantly decreased in insulin-dependent diabetes mellitus (8.4 +/- 0.5 and 22.5 +/- 1.1 pmol/10(6) RBC/min) and non-insulin dependent diabetes mellitus (7.3 +/- 1.0 and 18.6 +/- 1.8 pmol/10(6) RBC/min) compared to healthy controls (9.3 +/- 1.0 and 24.6 +/- 1.1 pmol/10(6) RBC/min). Maximal Ca2+ ATPase activity showed a significant correlation to systolic blood pressure in both insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus. There was no significant correlation of maximal Ca2+ ATPase activity to fasting serum glucose concentration and to HbA1 levels. Maximal Ca2+ ATPase activity was significantly correlated to creatinine clearance in non insulin-dependent diabetes mellitus, but not in insulin-dependent diabetes mellitus. It is concluded that a decreased cellular Ca2+ ATPase activity may predispose to the development of hypertension in diabetes mellitus. PMID- 7875652 TI - Circulating soluble IL-2 receptor levels are low in patients with hypothyroid autoimmune thyroiditis. AB - In hypothyroid patients serum soluble IL-2 receptor levels showed scattered and conflicting results. In our report we studied circulating soluble interleukin 2 receptors in 22 patients with hypothyroid autoimmune thyroiditis before L thyroxine treatment and when the patients became euthyroid. The mean of soluble Interleukin 2 receptor levels in the hypothyroid state was 48.6 pmol/l (95% confidence interval, 45.6-51.5) statistically lower than in the controls (95% confidence interval, 86.4 pmol/l, 83.3-89.4) (p < 0.0001). When the patients became euthyroid during L-thyroxine treatment, soluble Interleukin 2 receptor levels increased, showing mean values comparable to the controls. A positive high correlation (p < 0.001) was observed between soluble Interleukin 2 receptor levels and thyroxine free levels in the hypothyroid as well as in the euthyroid state and between soluble Interleukin 2 receptors and the mean weekly L-thyroxine dose. Our study confirmed that in the hypothyroid state, the behaviour of soluble Interleukin 2 receptors is anomalous as compared to other autoimmune diseases. In fact a strict relationship exists between the levels of thyroid hormones and soluble Interleukin 2 receptors but not between the latter and antithyroid antibodies. These results agree with those supporting a role for thyroid hormones in the regulation of the immune system. They also suggest that the measurement of soluble Interleukin 2 receptors could be used as a marker of the peripheral action of thyroid hormones. PMID- 7875653 TI - Androgen-related effects on peripheral glucose metabolism in women with congenital adrenal hyperplasia. AB - The study was designed to investigate the influence of androgens on peripheral glucose metabolism in women with congenital adrenal hyperplasia (CAH). Nine normal women and seven women with CAH were studied (4 with the classical form of 21-hydroxylase deficiency [C 21-OH] and 3 with nonclassical 21-hydroxylase deficiency [NC 21-OH]). The study was performed using the forearm model combined with local indirect calorimetry. The insulin level reached 30 minutes after glucose ingestion was significantly greater (p < .05) in patients with CAH. The patients with C 21-OH had elevated androstenedione (A) and testosterone (T) and low DHEA-S and presented a 35% greater insulin response to a glucose stimulus than the control group, area under the curve (AUC) of 9457 +/- 887 vs 6989 +/- 833 microU/ml.3 hours. Patients with NC 21-OH had slightly elevated T, A and DHEA S and presented an insulin response that was similar to the control group, AUC = 7208 +/- 1935 microU/ml.3 hours. Despite the greater muscle mass of the patients with CAH the forearm glucose uptake during the three hours of the study was lower in these patients than in normal women (CAH = 100.9 +/- 10.0 vs control group = 132.5 +/- 21.2 mg/100 ml forearm). The ratio of insulin response to the increment of forearm glucose uptake over a period of 3 h was significantly higher in patients with CAH (control group = 59.6 +/- 6.5 vs CAH = 98.6 +/- 19.4 microU.ml 1/mg.100 ml forearm-1, p < 0.05). These results suggest that insulin sensitivity is decreased in patients with CAH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875654 TI - Effects of nocturnal and diurnal food deprivation on pancreas weight, pancreas insulin content and serum glucose and insulin levels in young weaned rats. PMID- 7875655 TI - Seasonal variations in corticosteroid-binding globulin levels in white laboratory and Norway rats. PMID- 7875656 TI - Response of cytosolic free calcium to angiotensin II in individual rat mesangial cells cultured in a medium high in glucose. PMID- 7875657 TI - Fructose 3-phosphate content of erythrocytes from patients with diabetes. PMID- 7875658 TI - Strong, sustained hepatocellular proliferation precedes hepatocarcinogenesis in hepatitis B surface antigen transgenic mice. AB - Hepatocyte turnover rates were studied in two lineages of transgenic mice that overproduce the hepatitis B virus (HBV) large envelope protein and retain filamentous hepatitis B surface antigen (HBsAg) particles in the endoplasmic reticulum, resulting in the formation of ground glass hepatocytes. The high producer lineage (50-4) develops a necroinflammatory liver disease that progresses to hepatocellular carcinoma (HCC), whereas the low producer lineage (107-5) displays no histopathologic changes other than ground glass hepatocytes. Bromodeoxyuridine (BrdU)-labeling studies of S-phase hepatocytes provide quantitative evidence for a strong, sustained proliferative response in the hepatocytes in lineage 50-4 that occurs after the onset of hepatocellular injury but long before the development of liver cell tumors. In contrast, the level of hepatocellular proliferation in lineage 107-5 is the same as nontransgenic controls. The findings support the concept that sustained hepatocellular proliferation plays an important role in the development of hepatocellular carcinoma (HCC). PMID- 7875659 TI - Low frequency of precore hepatitis B virus mutants in anti-hepatitis B e-positive reactivation after loss of hepatitis B e antigen in patients with chronic hepatitis B. AB - The objective of this study was to evaluate the role of hepatitis B virus (HBV) precore mutations in patients with anti-HBe-positive chronic hepatitis B with or without previous known HBe antigen (HBeAg) viremic phase, and to assess the potential implication of precore mutants in HBeAg-negative reactivation after loss of HBeAg. Nineteen patients were studied: 7 had a previous HBeAg-positive phase and had spontaneous or therapeutically induced loss of HBeAg (group A); 12 had no previous HBeAg-positive phase (group B). Direct sequencing of PCR products was performed on serum collected during the anti-HBe-positive phase in the two groups. In group A, precore sequencing showed that 5 patients were infected by wild-type virus, 1 patient was infected with a precore mutant, and 1 patient was found to be infected by a mixture of wild-type and precore mutant viruses. In group B, precore sequencing showed that only 1 patient was infected with wild type virus and that 11 were infected with precore mutants. In a few patients, the presence of HBeAg within immune complexes may explain HBeAg negativity. In conclusion, our results show that, in patients with anti-HBe-positive chronic hepatitis B: (1) precore mutations creating a stop codon are more frequently found in those without known previous HBeAg positivity; (2) after loss of HBeAg, the patients who have anti-HBe-positive reactivation are infected by wild-type virus, which suggests that reactivation is not related to precore mutations; (3) HBeAg negativity may be caused by immune complexes formation. PMID- 7875660 TI - Mapping of immunodominant CD4+ T lymphocyte epitopes of hepatitis C virus antigens and their relevance during the course of chronic infection. AB - In acute and chronic viral disease the specific response of CD4+ T lymphocytes to certain viral proteins is an essential part of antiviral effector mechanisms. In hepatitis C virus infection, the contribution of the immune system and particularly of CD4+ T lymphocytes to the pathogenesis of disease is unknown. We serially determined the peripheral blood CD4+ T lymphocyte response to several recombinant hepatitis C virus proteins (core, NS3, NS4, NS5) and 17 overlapping synthetic peptides derived from the core sequence over up to 48 months in 43 patients with chronic hepatitis C; of these, 16 had been treated with interferon alfa (IFN). Twelve of 27 untreated patients, 4 of 4 sustained responders to IFN, 7 of 8 patients with a transient response, and 1 of 4 nonresponders showed a proliferative response to hepatitis C virus proteins. The hepatitis C virus core protein was the most immunogenic protein, and fine analysis with peptides indicated amino acids 23 to 42, 66 to 85, and 131 to 150 as immunodominant regions. In a subgroup of nine patients, proliferation assays were performed before or during IFN. In this subgroup, sustained responders but not those with a transient or no response to IFN showed a specific CD4+ immune reaction to hepatitis C viral antigens (P < .05). Infection with hepatitis C virus genotype 3a was significantly associated with a sustained response to IFN (P < .05). In general, a CD4+ T lymphocyte response was more common in patients with chronic hepatitis C who responded to interferon-alpha as compared with nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875661 TI - Breakthrough during recombinant interferon alfa therapy in patients with chronic hepatitis C virus infection: prevalence, etiology, and management. AB - Recombinant interferon alfa (r-IFN alpha 2) has been shown to normalize the aminotransferase levels in approximately 50% of patients with chronic hepatitis C virus (HCV). Few patients experience a relapse during the treatment, in spite of a complete initial response (breakthrough). We studied 191 HCV Ab-positive patients with histologically proven chronic hepatitis. All of them were treated with r-IFN alpha 2 (3 MU three times a week). A complete response was seen in 54.4%. However, 12 of 104 responders experienced a breakthrough. At the time of breakthrough, neutralizing IFN antibodies were positive in 6 of 12 patients. Binding IFN antibodies were positive in all of these 12 patients. Continued treatment with r-IFN alpha 2, even at higher doses, did not restore the previous response in any patient. All of them were then switched to natural lymphoblastoid IFN, and this rapidly restored a complete response in all of the patients. PMID- 7875662 TI - Incidence of hepatocellular carcinoma in chronic hepatitis B and C: a prospective study of 251 patients. AB - The incidence of hepatocellular carcinoma (HCC) was prospectively studied in 251 chronic hepatitis patients, and was compared between the 127 cases of hepatitis B and 124 cases of hepatitis C. All patients were diagnosed by needle biopsy on entering the study, and the cases consisted of chronic persistent hepatitis (CPH), chronic active hepatitis (CAH)2a, and CAH2b (cirrhosis was not included). Of the cases of chronic hepatitis B, 5 cases of HCC (3.9%) were detected; among the chronic hepatitis C cases, 13 cases (10.4%) were detected. Thus, although the mean follow-up periods were in the same range, the incidence of hepatocellular carcinoma was 2.7 times higher in hepatitis C than in hepatitis B (chi 2 = 3.116, P < .05). Using the Kaplan-Meier method, the incidence of HCC was significantly higher in chronic hepatitis C (P = .0194, generalized Wilcoxon test). In hepatitis C, the incubation period until HCC was detected was shorter when the liver disease was more advanced. Such a tendency was not observed in hepatitis B. In the 13 cases of HCC occurring in chronic hepatitis C, noncirrhotic liver was seen in only 1 case (7.7%), whereas 2 of the 5 cases of HCC (40%) in chronic hepatitis B were noncirrhotic. The prevalence of hepatitis C virus (HCV) genotypes II and III was the same in the total followed cases and HCC cases. PMID- 7875663 TI - The natural history of gallstones: the GREPCO experience. The GREPCO Group. AB - During the cross-sectional studies (February 1981 to July 1984) performed by the Group for Epidemiology and Prevention of Cholelithiasis (GREPCO) in Rome, Italy, 161 subjects were identified as having gallstones. Ten subjects did not participate in the prospective follow-up. At entry, 33 of the 151 remaining subjects were symptomatic, and 118 were asymptomatic. Data on incidence of biliary colics, complications, cholecystectomy, and death were collected at least every 2 years. In the initially asymptomatic group, the cumulative probability (% +/- SE) of developing biliary colic was 11.9 +/- 3.0 at 2 years, 16.5 +/- 3.5 at 4 years, and 25.8 +/- 4.6 at 10 years. None of the variables considered as possible modifiers of the natural history were found to be associated with an increased risk of developing biliary colic. The cumulative probability (% +/- SE) of developing complications after 10 years was 3.0 +/- 1.8 in the initially asymptomatic group and 6.5 +/- 4.4 in the symptomatic group (P = NS). Incidence of cholecystectomy was higher in the initially symptomatic than in the asymptomatic group (log-rank test = 2.27; P = .02). Fifteen (53.6%) of the 28 operated in the initially asymptomatic group were submitted to cholecystectomy, although specific symptoms did not occur. Twelve (10.2%) and 2 (6.1%) of the initially asymptomatic and symptomatic subjects died during the follow-up. One patient in the former group died at age 64 of a histologically proven adenocarcinoma of the gallbladder. In conclusion, this study demonstrates that the natural history of gallstones is less benign than is generally considered. PMID- 7875664 TI - Endoscopic therapy of sclerosing cholangitis. AB - The efficacy of endoscopic treatment in primary sclerosing cholangitis has not been clearly established. This report presents endoscopic intervention in 53 consecutive patients with this disorder. Pertinent data were abstracted from the GI-TRAC database, medical records, and cholangiograms, and clinical follow-up was obtained by telephone interview of the subjects. Assessed treatment outcomes were clinical symptom, liver function test, and cholangiographic appearance. Between 1986 and 1993, 85 patients with primary sclerosing cholangitis underwent successful ERCP, of which 36 men and 17 women underwent 100 therapeutic endoscopic procedures. Forty-three of 50 dilations, 37 of 38 stentings, 8 of 8 nasobiliary tube placements, and 11 of 17 stone extractions were technically successful. These treatments were complicated by cholangitis or pancreatitis in 15 patients. Clinical follow-up was obtained in 50 of 53 patients who had undergone 85 procedures (median follow-up of 31 months): 28 patients felt better, 21 felt the same, and 1 felt worse. Liver function tests obtained within 3 months of the endoscopic treatment were significantly improved compared with pretreatment values (P < .001). Cholangiograms showed improvement in 36% of the patients, no change in 51%, and the effect of therapy could not be assessed in 13%. Overall, 41 of 53 patients (77%) had improvements of their clinical symptoms, liver function tests, or cholangiograms. PMID- 7875665 TI - Escherichia coli capsular polysaccharide and spontaneous bacterial peritonitis in cirrhosis. AB - Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication of cirrhosis. Escherichia coli is the most frequent bacterium isolated in this condition. The presence of capsular antigens, mainly the K1 capsular polysaccharide, has been associated with invasiveness in E coli infections. Capsular serotypes of E coli causing SBP were determined in 37 cirrhotic patients. Twenty-seven strains were encapsulated (72.9%), 9 of them (24.3%) with K1 capsular polysaccharide, and 10 were nonencapsulated. Patients with encapsulated E coli showed a significantly higher incidence (92.5% vs. 50%; P < .01) and number of complications per patient (1.9 +/- 1.1 vs. 0.8 +/- 1.0; P < .01) than patients with nonencapsulated strains. Although mortality was higher in patients with encapsulated strains (44.4% vs. 20%), the difference did not reach statistical significance. Considering patients infected by encapsulated strains, the incidence of complications and mortality were similar in patients with or without K1 strains. These data suggest that the presence of encapsulated strains could have a prognostic significance in SBP caused by E coli in cirrhotic patients. PMID- 7875666 TI - Two different dosages of cefotaxime in the treatment of spontaneous bacterial peritonitis in cirrhosis: results of a prospective, randomized, multicenter study. AB - Cefotaxime (CTX) is considered one of the first-choice antibiotics in the therapy of spontaneous bacterial peritonitis (SBP) in cirrhosis. Because CTX is largely metabolized in the liver, this drug may also be effective in SBP by administering lower doses than those habitually used. To investigate this possibility, a prospective, randomized, multicenter study was performed to compare the therapeutic efficacy of two different dosages of CTX in 143 patients with SBP: 71 (group I) were allocated to receive a high dose (2 g every 6 hours, which is one of the most frequently recommended doses in this infection), and 72 (group II) were allocated to receive a low dose (2 g every 12 hours). At inclusion, both groups were similar in relation to clinical and laboratory data, with the exception of a higher incidence of positive ascitic fluid culture in group I than in group II (59% vs. 40%; P = .029). The rate of infection resolution was similar for both groups (77% vs. 79%). Hospital survival was also similar in both groups (69% vs. 79%). No difference was observed between patients with positive or negative ascitic fluid cultures with regard to infection resolution and patient survival. The duration of antibiotic therapy was similar in both groups (9.0 +/- 3.3 days in group I vs. 8.8 +/- 3.1 days in group II). In a subset of 13 patients from group I and 11 patients from group II CTX levels were determined in serum (peak and trough) and ascitic fluid (concomitantly with trough serum). Peak serum levels were similar in patients from both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875667 TI - Macroregenerative nodules in a series of adult cirrhotic liver explants: issues of classification and nomenclature. AB - Macroregenerative nodules (MRNs), probably representing a pathway for human hepatocarcinogenesis, are generally classified into type I MRNs (or ordinary adenomatous hyperplasia) and type II MRNs (or atypical adenomatous hyperplasia), on the basis of imprecise definitions of cytological and architectural atypia. It is currently believed that type II MRNs are probably true precursors of hepatocellular carcinoma (HCC), whereas type I lesions may simply represent large regenerative nodules. A series of 155 consecutive adult cirrhotic liver explants were examined for evidence of MRNs, HCC, and liver cell dysplasia (LCD) of large and small cell types, and their appearance, in terms of proposed classification schemes, was reviewed. There was evidence indicating that the presence of either type of MRN was associated with an increased incidence of HCC (all MRNs, P < .00019; type I MRNs, P < .067; type II MRNs, P < .012) compared with cirrhotic livers without MRNs. A subset of younger patients with a large (uncountable) number of MRNs in their livers, who did not show any increased incidence of carcinoma, was identified. Excluding these cases from statistical analysis, all associations were strengthened, implying either that malignant progression had not had time to occur in this younger population or that these nodules were simply large regenerative nodules without malignant potential. MRNs from these livers were histologically indistinguishable from MRNs occurring in more limited numbers, although atypical changes other than large cell type LCD were less frequent. No independent association between LCD of large cell type and HCC was found in the entire series.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875668 TI - Transjugular intrahepatic portosystemic shunts for refractory ascites: assessment of clinical and hormonal response and renal function. AB - Cirrhosis is frequently complicated by ascites that may become resistant to diuretic therapy. Transjugular intrahepatic portosystemic shunts (TIPS) represent a new treatment for this debilitating condition. The aim of this study was to ascertain the clinical efficacy of TIPS, as well as its impact on renal function and on hormonal parameters. Five inpatients with refractory ascites were studied prospectively before TIPS, and 3 and 14 days after TIPS. After TIPS, ascites completely resolved or was minimal in all patients. Diuretics were discontinued in three subjects and decreased by at least 50% in two. One patient developed liver failure after TIPS and required liver transplantation; the others remained stable after a mean follow-up of 14 months. Mean urinary sodium excretion increased from 2.1 +/- 0.6 mEq/24 hr before TIPS to 13.0 +/- 4.3 mEq/24 hr 14 days after TIPS. Mean serum creatinine and glomerular filtration rate also tended to improve during the study period. With the exception of the patient who developed liver failure, plasma aldosterone concentration decreased from a mean of 126.0 +/- 29.9 ng/dL to 22.8 +/- 6.8 ng/dL (P = .04), and plasma renin activity decreased from a mean of 9.0 +/- 3.0 micrograms/L/h to 0.9 +/- 0.1 microgram/L/h (P = .08). Additionally, 19 patients who underwent TIPS for refractory ascites outside of this protocol were followed prospectively for a mean of 282 days. Clinical improvement in ascites control was noted in 74%, and the mean dose of diuretics was decreased by more than 50%. Nonresponders more often had underlying renal disease. In conclusion, TIPS is an effective therapy for refractory ascites in most patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875669 TI - Systemic hemodynamic, forearm vascular, renal, and humoral responses to sustained cardiopulmonary baroreceptor deactivation in well-compensated cirrhosis. AB - The aim of this study was to assess baroreceptor function in well-compensated cirrhosis by determining the forearm vascular, renal, and humoral responses to sustained baroreceptor deactivation. The effect of sodium status on baroreceptor function was also assessed. Eight cirrhotic patients and 10 age- and sex-matched controls were studied twice after a 20 mmol and 200 mmol of sodium/d diet for 7 days. Systemic and renal hemodynamics, renal sodium handling, forearm blood flow, and neurohumoral factors were assessed before, during, and after the application of lower body negative pressure (LBNP) for 1 hour. Controls and cirrhotic patients had similar baseline mean arterial pressure, heart rate, forearm and renal hemodynamics. High-sodium intake resulted in suppression of sympathetic nervous activity in the controls (plasma norepinephrine, 1.06 +/- 0.11 nmol/L on low vs. 0.76 +/- 0.08 nmol/L on high sodium; P = 0.01) but not in the cirrhotic patients (1.35 +/- 0.22 nmol/L on low vs. 1.26 +/- 0.11 nmol/L on high sodium; P > 0.05). Both groups responded to LBNP with significant further increases in plasma norepinephrine, resulting in significant decreases in forearm blood flow on both sodium diets. Controls also responded with a significant worsening of renal hemodynamics on low-sodium diet only, but this was not observed in the cirrhotic patients on either diet. Therefore, in well-compensated cirrhotic patients: (1) sympathetic activation occurs despite an adequate, effective arterial filling, and this may contribute to sodium retention; and (2) baroreceptor function is normal. Apparent end organ unresponsiveness within the renal circulation may account for the lack of renal hemodynamic changes to reflex sympathetic stimulation. PMID- 7875670 TI - Prevalence, severity, and risk factors of liver disease in blood donors positive in a second-generation anti-hepatitis C virus screening test. AB - In a cohort of 483 blood donors positive for antibody to hepatitis C virus on second-generation enzyme-linked immunosorbent, the confirmatory second-generation recombinant immunoblot assay (Ortho Diagnostic Systems) was positive in 172 cases (36%), indeterminate in 113 (23%), and negative in 198 (41%). We further studied 94 of the donors (recombinant immunoblot assay positive in 85, indeterminate in 6, and negative in 3). Alanine transaminase (ALT) activity, assayed on three occasions, was elevated in at least one assay in 85% of the 85 recombinant immunoblot assay-positive donors. Liver disease was present in 95% of these patients (chronic persistent hepatitis, 35%; chronic active hepatitis, 53%; cirrhosis, 7%). Ten of the 13 recombinant immunoblot assay-positive donors with normal ALT activity had liver disease; polymerase chain reaction testing for viral RNA was predictive of liver disease in most cases. Donors with cirrhosis differed significantly from cirrhosis-free donors in terms of age, sex ratio, ALT activity, and excessive alcohol consumption. Three of the 6 recombinant immunoblot assay-indeterminate donors (isolated C 22) who underwent histological examination had elevated ALT activity and liver disease. The 3 recombinant immunoblot assay-negative donors evaluated were free of liver disease. This study shows that anti-HCV second-generation enzyme-linked immunosorbent positivity is confirmed in fewer than 40% of blood donors by the second-generation recombinant immunoblot assay, and that liver disease is present in 95% of recombinant immunoblot assay-positive donors. Recombinant immunoblot assay positivity combined with viremia is frequently associated with the existence of liver disease, regardless of transaminase activity. Excessive alcohol consumption may be an important factor in the onset of cirrhosis in anti-HCV-positive blood donors. PMID- 7875671 TI - Endothelin-1 and -3 plasma concentrations in patients with cirrhosis: role of splanchnic and renal passage and liver function. AB - Increased as well as decreased plasma concentrations of the endothelins, endogenous vasoactive peptides, have been reported in cirrhosis. This might be caused by alterations of hepatic or renal clearance or release. Therefore, the aim of the current study was to investigate the influence of splanchnic and renal passage and of liver function on plasma concentrations of endothelin-1 (ET-1) and endothelin-3 (ET-3) in patients with cirrhosis compared with controls. Eighteen patients with cirrhosis and 8 normotensive controls of similar age were investigated. Arterial and venous plasma samples were obtained simultaneously, and ET-1 and ET-3 concentrations were determined in extracted plasma by two separate radioimmunoassays. Arterial as well as hepatic and renal venous concentrations of ET-1 in cirrhosis (17.8 +/- 0.8 pg/mL, 19.1 +/- 0.9 pg/mL, and 16.8 +/- 0.8 pg/mL) were significantly (P < .001) higher than in controls (9.2 +/ 1.7 pg/mL, 9.0 +/- 2.0 pg/mL, and 8.4 +/- 1.9 pg/mL, respectively). The same held true for the corresponding ET-3 plasma concentrations in cirrhosis (19.3 +/- 1.6 pg/mL, 20.5 +/- 1.5 pg/mL, and 18.4 +/- 1.5 pg/mL, respectively) compared with controls (11.1 +/- 1.8 pg/mL, 11.3 +/- 1.5 pg/mL, and 10.1 +/- 1.7 pg/mL, respectively; P < .01). There was a significant (P < .05) renal net extraction of ET-1 and ET-3 in cirrhosis. In contrast, a significant (P < .05) net release of ET-1 and ET-3 (2.40 +/- 0.80 ng/min and 1.75 +/- 1.16 ng/min) during splanchnic passage was observed in cirrhosis, but not in controls (-0.24 +/- 0.51 ng/min, and -0.46 +/- 0.64 ng/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875672 TI - Isolation and purification of large quantities of fresh human Kupffer cells, which are cytotoxic against colon carcinoma. AB - A new rapid method is described for the isolation and purification of functional active human Kupffer cells without the need of in situ perfusion techniques. Liver wedge biopsies (3 to 5 g), obtained after laparotomy, were incubated with pronase under continuous pH registration. Human Kupffer cells were subsequently separated from other nonparenchymal cells by Nycodenz gradient centrifugation and purified by counterflow centrifugal elutriation. Kupffer cells, 1.7 +/- 0.4 x 10(6) per gram liver, were isolated with a purity of 95% +/- 3%. Cell-mediated cytotoxicity of Kupffer cells was assayed against a human colon carcinoma cell line (SW948). Kupffer cell cytotoxicity was 42% +/- 9% (mean +/- SD) at an effector-to-target cell ratio of 10 and significantly increased to 73 +/- 17% (P < .05) after activation of Kupffer cells with interferon-gamma. In conclusion, a reliable and relatively simple method is provided to isolate and purify fresh human Kupffer cells in large yields, which show spontaneous as well as gamma interferon-induced cytotoxicity against a human colon carcinoma cell line. PMID- 7875673 TI - Expression of the hepatitis C virus genome in rat liver after cationic liposome mediated in vivo gene transfer. AB - The lack of a small animal model of hepatitis C virus (HCV) infection has impeded elucidation of the pathogenesis of HCV. The aim of this study was to develop an HCV-expressing animal model by means of cationic liposome-mediated in vivo gene transfer. To examine the feasibility of this strategy, pActLacZ, an expression vector composed of the LacZ gene driven by the beta-actin promoter, complexed with lipofectin, was injected retrogradely into the common bile ducts of adult rats. X-Gal histochemical staining clearly showed that the LacZ gene was expressed in hepatocytes, but not in biliary epithelial cells. Maximal expression was observed at a DNA to lipofectin ratio of 1:4. Based on this observation, pAGS3M091, an expression vector containing the full length of HCV complementary DNA (cDNA) preceded by the beta-actin promoter, was evaluated. Two days after in vivo intrabiliary administration of pAGS3M091 complexed with lipofectin, polymerase chain reaction (PCR) amplification of reverse-transcribed liver RNA demonstrated the 5' and 3' portions of HCV transcripts derived from pAGS3M091. Immunohistochemical analysis showed the HCV core protein in a small number of hepatocytes scattered in the hepatic lobules. We conclude that the full-length HCV genome was successfully expressed in adult rat liver by means of cationic liposome-mediated in vivo gene transfer. This model will be useful for determining the immunopathological role of HCV in vivo. PMID- 7875674 TI - Ex vivo hepatic gene transfer in mouse using a defective herpes simplex virus-1 vector. AB - A defective amplicon herpes simplex virus-1 (HSV-1) vector, HSVlac, was used to transfer an E. coli lacZ reporter gene into primary hepatocytes. The lacZ gene was driven by the HSV immediate early (IE) 4/5 promoter. Use of the HSVlac vector resulted in highly efficient gene transfer. Because difficulties in culturing primary hepatocytes impose limitations in ex vivo gene therapy, we sought to determine whether use of the HSVlac vector could simplify gene transfer. Therefore, we incubated HSVlac with primary hepatocytes in suspension and found that the lacZ gene was still transferred with great rapidity and efficiency. To examine lacZ expression in transduced hepatocytes in vivo, we used a mouse hepatocyte transplantation system. In congeneic recipients of primary hepatocytes transduced with HSVlac in suspension, the lacZ gene was expressed in liver and spleen up to 2 weeks. However, survival of transplanted hepatocytes, as well as persistence of HSVlac genome in recipient organs, was demonstrated for up to an 11-week duration of the experiment. These findings suggest that in vivo regulation of the HSV IE4/5 promoter was responsible for the short-term expression of lacZ, which should be overcome by the use of liver-specific promoters. Therefore, our results indicate the feasibility of hepatic gene transfer with a defective HSV-1 vector. PMID- 7875675 TI - Transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta 1 receptors in normal, cirrhotic, and neoplastic human livers. AB - Transforming growth factor-Beta 1 (TGF-beta 1) is an important mediator of control of liver cell proliferation and replication. The aim of the current study was to compare TGF-beta 1 gene expression, protein synthesis, and cell membrane receptors in normal liver, cirrhotic nodules, and neoplastic human livers. Five surgical resections for metastasis in an otherwise normal liver and 25 resections for hepatocellular carcinoma with cirrhosis were included in this study. Messenger RNA (mRNA) and TGF-beta 1 protein were detected on serial tissue sections of normal, cirrhotic, and tumoral livers using in situ hybridization and immunohistochemistry. TGF-beta 1 type II receptors were detected on tissue sections using immunohistochemistry. In normal livers, TGF-beta 1 mRNA and protein were not significantly expressed. In cirrhotic nodules, a few sinusoidal cells and mesenchymal cells of fibrous septa displayed TGF-beta 1 mRNA. By immunohistochemistry, protein was detected in the extracellular matrix along the fibrous septa. Hepatocytes from normal and cirrhotic livers did not express TGF beta 1. In contrast, the cytoplasm of hepatocytes in neoplastic nodules showed intense staining for TGF-beta 1 mRNA and protein. Although TGF-beta 1 receptor II was expressed on the plasma membrane of normal liver cells, tumoral hepatocytes no longer displayed membrane labeling but rather diffuse intracytoplasmic staining with perinuclear accumulation. This study suggests that the escape of tumoral hepatocytes from control of cell proliferation by TGF-beta 1, despite its overexpression by these cells, might be related to a defect in TGF-beta 1 receptor II processing on the liver cell membrane. PMID- 7875676 TI - Spontaneous acceptance of rat liver allografts is associated with an early downregulation of intragraft interleukin-4 messenger RNA expression. AB - Liver allografts are not rejected in the fully incompatible Lewis-RT1(1) (LEW) to blood group D Agouti-RT1a (DA) rat strain combination despite an early infiltration by recipient mononucleated cells that initially display a phenotype, an ability to respond to interleukin-2 (IL-2) and donor-specific cytotoxicity indistinguishable from that observed in the rejected, DA to LEW combination. To further analyze the mechanism of this tolerance, we have compared in these two combinations, as well as in syngeneic grafts and in normal livers, the presence of intrahepatic cytokine transcripts (IL-1 alpha, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor [TNF]-alpha, TNF-beta, and transforming growth factor [TGF]-beta) by a semiquantitative polymerase chain reaction (PCR) or by northern-blotting. In normal livers or syngeneic grafts, IL-1 alpha, TNF-beta, and TGF-beta were the only cytokines detected by these methods. The levels of all cytokine transcripts were increased in allogeneic grafts. Expression of cytokine transcripts was very similar in the two allogeneic strain combinations except IL-4, which was expressed at a much lower level in the nonrejected strain than in the rejected strain from day 2 onward. We conclude that selective downregulation of IL-4 gene expression is associated with, and a potential mediator of, the induction of tolerance in this model. PMID- 7875677 TI - Increased expression of matrix metalloproteinase-II in experimental liver fibrosis in rats. AB - Matrix metalloproteinase-II (MMP-II, 72-kd type IV collagenase, or gelatinase) is one of the gene families of zinc enzymes capable of degrading extracellular matrix molecules, and specifically of degrading type IV and V collagens, gelatin, fibronectin, and elastin. In this study, we used both the liver fibrosis model and the reversibility model of experimental cirrhosis to clarify how MMP-II participates in liver fibrosis of rats. To produce fibrosis model, rats received subcutaneous injections of CCl4 twice weekly for 7, 9, or 14 weeks. For the reversibility model, rats were treated with CCl4 three times a week for 8 weeks and killed at 3, 7, 14, 28, or 42 days after discontinuation of treatment. MMP-II gene expression was studied by Northern hybridization technique, and gelatinase activity of MMP-II was examined by zymography using gelatin substrate. At the same time, an immunohistochemical study using anti-type IV collagen antibody was carried out. In liver fibrosis model, nodule formation was established at 14 weeks. Immunodeposit of type IV collagen was increased in wide fibrous septa and was clearly observed along sinusoidal wall. Gene expression of MMP-II increased up to 7 to 12 times compared with that of controls, with the expression rate being maximum at an intermediate stage of fibrosis. Zymography showed the expressions of both 65-kd latent MMP-II, which is confirmed to be activated by adding p-aminophenylmercuric acetate, and 62-kd active MMP-II during fibrosis. The expression of both forms increased 13 to 28 times as the fibrosis progressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875678 TI - An anesthetized model of lethal canine galactosamine fulminant hepatic failure. AB - A reproducible large animal model of fulminant hepatic failure was developed in the anesthetized dog by the administration of the amino sugar D-galactosamine. Galactosamine in 5% dextrose in water (D5W), was given as an intravenous bolus to 10 young male dogs weighing 27 to 30 kg. Three dogs that received an equal volume of D5W alone served as controls. Galactosamine at 0.5 g/kg (n = 5) produced significant biochemical evidence of liver injury with 100% survival at 48 hours. Galactosamine 1.0 g/kg (n = 5) yielded in 100% 48-hour mortality resulting from fulminant liver failure characterized by a progressive increase in liver enzymes, total bilirubin, ammonia, and lactate and associated coagulopathy, hypoglycemia, coma, and increased intracranial pressure. Necropsy showed liver pallor, ascites, and brain swelling. Liver histology showed significant hepatocellular necrosis. This clinically relevant large animal model will enable the quantitative evaluation of new technologies, such as the bioartificial liver, for the support of hepatic failure in humans. PMID- 7875679 TI - Transformation of sinusoids into capillaries in a rat model of selenium-induced nodular regenerative hyperplasia: an immunolight and immunoelectron microscopic study. AB - The oral administration of selenium (Se) to young rats induces, over a 2-month period, the formation of nodular regenerative hyperplasia with sinusoidal damage around nodules. Perinodular areas located in zone 1 comprise atrophic hepatocytes and capillarized sinusoids without fibrosis. We used this unique model of capillarization without fibrosis to investigate the temporal relationship between the process of capillarization and changes occurring in the deposition of components of the extracellular matrix. After 2 weeks of intoxication, type III collagen and fibronectin were stable, but laminin and type IV collagen had increased in zone 1, resulting in the formation of septae between portal tracts. Even at 8 weeks, these two components still formed the principal deposits in perinodular zones. Electron microscopy showed already at 1 week in zone 1 that part of the endothelial wall had detached from hepatocytes. Sinusoidal endothelial cells progressively acquired certain of the characteristics of a vascular endothelium, some proliferated, and perisinusoidal cells transformed into myofibroblasts, surrounded by deposits of laminin and type IV collagen. These results indicate that both laminin and type IV collagen are involved in capillarization without fibrosis and in angiogenesis; fibronectin would not seem to play a role. PMID- 7875680 TI - Therapeutic serum concentrations of human alpha-1-antitrypsin after adenoviral mediated gene transfer into mouse hepatocytes. AB - Alpha-1-antitrypsin is a relatively common genetic deficiency that results in early emphysema. The liver as the natural source of most alpha-1-antitrypsin synthesis was the target organ selected for gene replacement therapy studies. Previous work used recombinant retroviral vectors that encode the human alpha-1 antitrypsin cDNA for ex vivo and direct in vivo transduction of hepatocytes in dogs and rodents. This approach led to low levels of human protein in the serum of recipients. In this study, recombinant adenoviral vectors that express the human alpha-1-antitrypsin cDNA under the transcriptional control of the phosphoglycerate kinase (PGK) or RSV-LTR promoters have been constructed and used for the direct transduction of mouse hepatocytes in vivo. The animals transduced with the recombinant adenoviral vectors had therapeutic serum levels of human alpha-1-antitrypsin of up to 700 micrograms/mL. Thus, adenovirus-mediated gene transfer of the hAAT cDNA into the liver was able to produce therapeutic serum concentrations of protein. PMID- 7875681 TI - Extracorporeal high-intensity focused ultrasound for VX2 liver tumors in the rabbit. AB - High-Intensity Focused Ultrasound (HIFU) can produce radical tissue necrosis. We wanted to assess tumor destruction, proliferation, and tumorigenesis after HIFU, in an animal model of hepatic tumor. New Zealand rabbits bearing VX-2 solitary liver tumors were treated with extracorporeal HIFU under ultrasound (US) guidance and standardized conditions. Groups differed only for the administration of either one or two consecutive HIFU procedures. Tissue destruction was assessed by stereomicroscopy and planimetry, cell proliferation was estimated by in vivo intra-arterial injection of 1200 muCi [3H]thymidine, and tumorigenesis was tested by reimplantation of treated or untreated pieces of liver tumors into the thighs of nontumor-bearing animals. Mortality was 0. Tumor destruction rates were 76.3% +/- 16% after one procedure and 94.2% +/- 7.3% after two procedures. Nuclear staining was heavy in control tumors and was absent in treated tumors. Untreated hepatic tumors induced measurable tumors at 3 weeks in thighs of all recipients, 7.8 +/- 2.4 cm3 in volume. Hepatic tumors treated with one HIFU procedure induced tumors in the thigh of recipients in 31.3% of cases (0.47 +/- 0.06 cm3), and those treated with two HIFU procedures induced tumors in 0% even after 8 weeks of follow-up. In conclusion, HIFU allows a noninvasive approach to the destruction of liver tumors in this model, with little toxicity but significant effects on proliferation and tumorigenesis. The repetition of HIFU procedures may improve results. PMID- 7875682 TI - Conditional immortalization of Gunn rat hepatocytes: an ex vivo model for evaluating methods for bilirubin-UDP-glucuronosyltransferase gene transfer. AB - Viral vectors and protein carriers utilizing asialoglycoprotein receptor (ASGR) mediated endocytosis are being developed to transfer genes for the correction of bilirubin-UDP-glucuronosyltransferase (bilirubin-UGT) deficiency. Ex vivo evaluation of these gene transfer vectors would be facilitated by a cell system that lacks bilirubin-UGT, but expresses differentiated liver functions, including ASGR. We immortalized primary Gunn rat hepatocytes by transduction with a recombinant Moloney murine leukemia virus expressing a thermolabile mutant SV40 large T antigen (tsA58). At 33 degrees C, the immortalized hepatocyte clones expressed SV40 large T antigen, synthesized DNA, and doubled in number every 2 to 3 days. At this temperature, differentiated hepatocyte markers, e.g., albumin, ASGR, and androsterone-UGT, were expressed at 5% to 10% of the levels found in primary hepatocytes maintained in culture for 24 hours. Glutathione-S-transferase Yp (GST-Yp), an oncofetal protein, was expressed in these cells at 33 degrees C, but was undetectable in primary hepatocytes. In contrast, when the cells were cultured at 39 degrees C or 37 degrees C, the large T antigen was degraded, DNA synthesis and cell growth stopped, and morphologic characteristics of differentiated hepatocytes were observed. The expression of albumin, ASGR, and androsterone-UGT, and their corresponding mRNAs, increased to 25% to 40% of the level in primary hepatocytes, whereas GST-Yp expression decreased. Functionality of ASGR was demonstrated by internalization of Texas red-labeled asialoorosomucoid, and binding and degradation of 125I-asialoorosomucoid. After liposome-mediated transfer of a plasmid containing the coding region of human bilirubin-UGT1, driven by the SV40 large T promoter, active human bilirubin-UGT1 was expressed in these cells. The immortalized cells were not tumorigenic after transplantation into severe combined immunodeficiency mice. These conditionally immortalized cells will be useful for ex vivo evaluation of bilirubin-UGT gene transfer vectors. PMID- 7875683 TI - Expression of SPARC in normal and fibrotic livers. AB - SPARC (secreted protein, acidic and rich in cysteine)--also known as osteonectin, BM-40, and 43K glycoprotein--is secreted by endothelial cells and fibroblasts in response to culture shock. SPARC has been found in association with tissues undergoing cell proliferation, migration, and extracellular matrix remodeling. We demonstrate that normal livers from humans, rats, and mice express substantial levels of SPARC messenger RNA (mRNA). Moreover, when compared with control specimens, significantly increased levels of SPARC mRNA were found in fibrotic livers from two animal models of liver disease: murine schistosomiasis and carbon tetrachloride-induced fibrosis in rats. Fibrotic human livers also had markedly increased levels of SPARC mRNA in comparison with normal livers. We also detected an increased production of SPARC protein in the liver of animals treated with carbon tetrachloride. By immunocytochemical analysis, SPARC protein was apparent in freshly isolated Ito cells. Hybridization studies showed Ito cells to be the main source of SPARC mRNA. Extracts from a Kupffer-endothelial cell fraction exhibited traces of SPARC transcript, but expression of SPARC mRNA was absent in extracts from freshly isolated hepatocytes. These studies demonstrate the increased expression of SPARC--a protein that modulates cell shape and disrupts cell-matrix interactions--during the initial stages of hepatic fibrosis. PMID- 7875684 TI - Acute endotoxin tolerance downregulates superoxide anion release by the perfused liver and isolated hepatic nonparenchymal cells. AB - This work is based on the hypothesis that low-dose lipopolysaccharide (LPS) suppresses the stimulatory and priming effects of a subsequent high-dose endotoxin on the formation of toxic oxygen-derived radicals by the perfused liver and isolated hepatic nonparenchymal cells. Such effects may in turn contribute to hyposensitivity to the lethal effect of large doses of endotoxin. Male Sprague Dawley rats received a nonlethal ("low-dose") intravenous injection of Escherichia coli LPS (0.5 mg/kg body weight) 12 to 120 hours before they were challenged by a "large dose" of endotoxin (10 mg/kg). Three hours after LPS challenge, the livers were perfused, and superoxide release was determined. Nonparenchymal cells were also isolated for the determination of superoxide anion formation in vitro. There was a low rate (0.14 +/- 0.1 nmol/min/g liver weight) of superoxide generated by the perfused livers from rats that received the low dose LPS 1 to 5 days previously. Control livers generated less than 0.08 nmol superoxide. A high rate (1.3 +/- 0.1 nmol/min/g) of superoxide release was measured in the perfused liver 4 hours after treatment of previously untreated control rats with large-dose LPS. This was attenuated to 0.7 +/- 0.04 nmol/min/g by an injection of low-dose LPS before challenge. This attenuation was time dependent; it failed to manifest at 12, 24, or 120 hours after low-dose LPS. Isolated endothelial cells, Kupffer cells, and sequestered hepatic neutrophils from rats given a high-dose LPS also generated significant amounts of superoxide both in the presence or absence of agonists, i.e., phorbol myristate acetate or opsonized zymosan.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875686 TI - Hepatology and hepatology: the trends continue. PMID- 7875685 TI - Lipoproteins and the liver sieve: the role of the fenestrated sinusoidal endothelium in lipoprotein metabolism, atherosclerosis, and cirrhosis. AB - The liver sieve, formed by the fenestrated hepatic sinusoidal endothelium, is a dynamic biofilter separating the hepatic blood from the plasma within the space of Disse. It filters macromolecules of differing sizes, especially lipoproteins. More specifically, it acts as a barrier to the large triglyceride-rich parent chylomicrons, while permitting the smaller triglyceride-depleted but cholesterol- and retinol-rich remnants to enter the space of Disse. There the remnants contact specific receptor sites on the hepatocyte microvilli. Thus, the liver sieve is the first site of hepatic selection and consequent metabolism of dietary cholesterol and fat-soluble vitamins, as well as rejection of dietary triglycerides. Therefore, perturbations of the porosity of the sieve, whether from changes in size, number of fenestrae, or composition of the underlying extracellular matrix within the space of Disse, will have a profound influence on the metabolism of lipoproteins. This disturbance of the homeostasis of lipids, including fat-soluble vitamins and cholesterol, as well as other macromolecules, may tilt the balance between health and disease in a variety of organs and tissues, such as the liver, kidney and arteries. PMID- 7875687 TI - Determining prognosis in patients with fulminant hepatic failure: when you absolutely, positively have to know the answer. PMID- 7875689 TI - The development of anti-hepatitis C virus agents. PMID- 7875688 TI - Hepatitis B virus escape mutants: "pushing the envelope" of chronic hepatitis B virus infection. PMID- 7875690 TI - Shifting visual attention in stereographic displays: a time course analysis. AB - According to a growing number of studies, the stereographic presentation of three dimensional information improves overall performance relative to displays with only monocular depth cues. Based on studies using real-world, three-dimensional stimuli, however, the efficiency (i.e., speed) of shifting attention between objects located at different depths is impaired relative to that of attention shifts between objects located at the same depth. In the present study we tested whether similar impairments occur when attention is shifted in stereographic space. We compared the time course of attention shifts across and within depth planes using a spatial cuing task. Contrary to the results from studies of real world stimuli, we found no difference between the time course of within-plane and across-plane attention shifts. PMID- 7875691 TI - Holistic peripheral processing of a polygon display. AB - Polygon displays compress information that would otherwise be conveyed by separate indicators into a single display in which each reading is represented by the distance of a polygon vertex from its center. The effect on detection of fault states of varying the number of polygon vertices from 4 to 20 in a display presented peripherally around a dynamic, simulated flight display was studied. Presence of the dynamic task reduced both speed and accuracy of response to the polygon display but did not significantly affect the pattern of response to differing numbers of vertices. All measures of performance were better with larger numbers of vertices. If the vertices are processed serially, more vertices require more processing time. Therefore, the result argues for holistic processing and implies that such information integration is beneficial to human performance in fault detection. PMID- 7875692 TI - Influence of extended wakefulness on automatic and nonautomatic processing. AB - We investigated the influence of extended wakefulness on automatic and nonautomatic processes in memory and visual search tasks. Subjects were trained in consistently mapped and variably mapped versions of each task, attaining automatic performance in the consistently mapped versions. We then recorded performance measures and event-related brain potentials for a 14-h period that began during the evening of the last day of training. Overall performance declined with extended wakefulness, but the benefits of consistently mapped training were retained throughout the night. Performance decrements consisted of an increase in nonresponses, increased response latencies, and decreased accuracies. P300 latencies increased, and P300 amplitudes decreased with extended wakefulness. When viewed together, reaction time and event-related brain potentials measures suggest that the locus of extended wakefulness effects was during early perceptual processes. PMID- 7875694 TI - Emerging from the last recession: dental economics. PMID- 7875693 TI - Young children's ability to climb fences. AB - Three studies were performed to evaluate the fence-climbing abilities of children who are in the high-risk age group for drowning in residential pools. Study 1 examined the ability of children in the age range of 24 to 54 months to climb commonly used fences (common chain link, small chain link, picket, iron, and stockade) at a 4-ft (1.22-m) height. Study 2 examined children's abilities to climb fences retrofitted with features that would potentially make them more difficult to climb. Study 3 examined children's abilities to climb 5-ft (1.52-m) fences. Results of the three studies show that the common chain-link fence is easy to climb even by two-year-old toddlers. Other fence types offered more effective barriers, especially for younger children. PMID- 7875695 TI - Invisible remodeling--the new way to improve dental office operations. PMID- 7875696 TI - Regional changes in the economics of dentistry. PMID- 7875697 TI - Heart rate variability. PMID- 7875698 TI - Angiotensin converting enzyme inhibitors in acute myocardial infarction. PMID- 7875699 TI - Left ventricular volume overload in isolated rheumatic mitral stenosis. AB - Having shown the absence of chronic preload insufficiency as the mechanism of modestly depressed left ventricular ejection performance in patients with rheumatic mitral stenosis in our previous work, we sought to characterise a subset of patients with left ventricular volume overload. Echocardiographically determined ventricular load, ejection and contractile performance and left ventricular geometry were studied in 19 patients with mitral stenosis having left ventricular volume overload (end-diastolic volume > 90 ml/m2, Group I) and in 83 patients with normal volume (end-diastolic volume < 90 ml/m2, Group II). The two groups were well matched for age, gender, body size and mitral valve area. Left ventricular ejection fraction was similar in the two groups; however, the patients in Group I had higher end-diastolic volume (101 +/- 15 vs 58 +/- 18 ml/m2, p < 0.0001), end-systolic wall stress (81.7 +/- 17 vs 64 +/- 22 Kdynes/cm2, p < 0.0001), left ventricular mass (109 +/- 20 vs 82 +/- 19 gm/m2, p < 0.001) but lower relative wall thickness (26 +/- 6 vs 34 +/- 9%, p = 0.007), mass/volume ratio (1.1 +/- 0.23 vs 1.49 +/- 0.46 gm/ml, p < 0.001) and wall stress/end-systolic volume ratio (2.07 +/- 0.58 vs 2.65 +/- 0.92, p = 0.016). Of these 19 patients in Group I, seven had isolated volume overload while 12 had associated eccentric hypertrophy. Wall stress correlated well with fractional shortening in Group II (r = 0.75, p < 0.001) but not in Group I (r = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875700 TI - Correlation of waist-hip ratio with coronary heart disease and risk factor prevalence in a rural male population. AB - Truncal obesity has been identified as a risk factor for coronary heart disease (CHD). We studied 399 males for waist hip ratio (WHR) measurement during a comprehensive cardiovascular survey in a rural population of Rajasthan. The WHR measurements were correlated with coronary risk factors and CHD prevalence. The mean WHR in the study population was 0.88 +/- 0.11. The median value was 0.88 with a range of 0.49 to 1.59. Multiple regression analysis showed a significant positive relationship of WHR with height (b = 0.77, p = 0.02), weight (b = 1.48, p = 0.02), body mass index (b = 1.44, p = 0.01) and systolic (b = 0.12, p = 0.05) and diastolic blood pressure (b = 0.13, p = 0.03) but not with age, educational level, total LDL- or HDL- cholesterol and triglycerides. The median value of 0.88 was taken to classify the study population for risk factor analysis. There were 200 males with WHR < or = 0.88 (Group A) and 199 males with WHR > or = 0.88 (Group B). Group B men had significantly higher body-weight and body-mass index and there was a trend towards lower serum HDL cholesterol and higher triglyceride levels in this group which was not statistically significant. The prevalence of hypertension was similar in the two groups. The prevalence of coronary heart disease was significantly higher in Group B. PMID- 7875701 TI - A study of platelet aggregation, thromboxane A2 and prostacyclin in central aortic and coronary sinus blood in ischemic heart disease. AB - Aortic and coronary sinus platelet aggregation, thromboxane A2 (TXA2) and prostacyclin (PG12) levels were studied in fourteen patients of stable angina (SA), six of vasopastic angina (VA) and six control subjects (C). Patients of SA were studied at rest and during incremental atrial pacing and patients with VA were studied at rest and during various stages of vasospasm. Platelet aggregation was studied with different working concentrations of ADP, epinephrine and collagen. TX A2 and PGI2 concentrations were estimated by measuring levels of their stable metabolites viz. thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (PGF1 alpha) respectively. Platelet aggregation was increased in SA and VA patients (p < 0.01) and further increase was seen during vasospasm (p < 0.001). However, it failed to increase on incremental atrial pacing. Similarly, TXB2 and PGF1 alpha levels were raised in SA and VA patients. While TXB2 further increased during vasospasm but not during atrial pacing. PGF1 infinity failed to rise with either. Thus platelets are in an activated state in SA and VA. This activated state is a cause and not an effect in SA and VA. An imbalance in the levels of TXA2 and PG12 could account for the vasospasm. PMID- 7875702 TI - Serotonergic mechanisms in heart failure. AB - A total of 29 subjects were studied which included 18 heart failure and 11 matched control cases. The underlying heart disease in heart failure cases was mostly chronic rheumatic valvular disease. The diagnosis of heart disease and heart failure was made on the basis of clinical examination, supplemented by electrocardiography, chest skiagram and echo cardiography. The serotonin status was assessed by measuring platelet serotonin uptake, intraplatelet serotonin content and whole blood 5-hydroxytryptamine (5-HT) levels. Blood platelet count was also done. In heart failure cases, platelet count were significantly less, the platelet 5-HT uptake and blood 5-HT levels remain unaltered. These findings indicate that platelet pool of serotonin does not contribute to raised serotonin blood levels in heart failure. The high blood serotonin levels may be due to either clearance defect or enhanced secretion from the gut or both. The altered serotonin kinetics in platelets also indicate a state of platelet activation in heart failure. PMID- 7875703 TI - Discrete subaortic stenosis: a study of 20 cases. AB - Twenty patients with discrete subaortic stenosis were studied during last 11 years. Cross sectional echocardiography and angiography demonstrated a membrane in 17 (85%), fibromuscullar collar in 2 (10%), and diffuse tunnel type of obstruction in 1 (5%) patient. Eighty five percent of patients had severe obstruction with average peak systolic gradients being 96.5 +/- 36.3 mm of Hg. Eight patients with membranous obstruction seen during the last 5 years underwent successful balloon dilatation with decrease in peak systolic gradient from 107.1 +/- 24.2 to 32.3 +/- 14.2. The haemodynamic benefits were sustained during 4 to 24 (mean 9.6) months followup. The results indicate that balloon dilatation can be a safe and effective treatment for thin subaortic membrane. Surgical resection is needed in patients with collar or tunnel type of obstruction. PMID- 7875704 TI - Blade and balloon atrial septostomy for creation of an adequate interatrial communication. AB - During a 7 year period from 1984 to 1991, 100 infants underwent either balloon atrial septostomy (BAS) (n = 92) or blade septostomy (BLS) (n = 8). The indication was complete transposition of the great arteries in all the patients. The mean age in the BAS group was 1.8 +/- 1.5 months while that in the infants requiring BLS due to a thick septum was 3.03 +/- 2.29 months. The degree of improvement in arterial oxygen saturation in both groups was satisfactory -27.16 +/- 14.06% in the BAS group vs 23.5 +/- 12.18% in the BLS group. There were no procedure related deaths in the BLS group, through only monoplane fluoroscopy was used in 6/8 patients. Three patients however died following balloon septostomy. We conclude that BLS is a safe and effective alternative to surgical septostomy when performed with due care. Two dimensional echocardiography during BAS enhances the speed and safety of the procedure and helps to identify patients who may require BLS due to a thick interatrial septum. PMID- 7875705 TI - Left main coronary artery compression by dilated main pulmonary artery in atrial septal defect. AB - Left main coronary artery compression by dilated pulmonary artery in patients with atrial septal defect has previously been reported, but not well characterized. Accordingly, we review retrospectively data of patients with atrial septal defect in whom selective coronary angiograms were done. 41 patients (26 females), aged 47.3 +/- 7.4 years were studied. The pulmonary artery mean pressure was 22.7 +/- 8.3 mm Hg and all patients had left to right shunt ratio of 2:1 or more (mean ratio: 3.9 +/- 1.7). Two patients (4.8%) had left coronary ostial stenosis. There were no clinical or haemodynamic parameters to differentiate the patients with or without these changes. Two patients (4.8%) had coexistent atherosclerotic coronary artery disease. In conclusion, left main coronary trunk compression rarely occurs in patients with atrial septal defect. This information may be relevant in evaluating patients with atrial septal defect. PMID- 7875706 TI - From coronary care to focussed care. PMID- 7875707 TI - Partial anomalous pulmonary venous drainage to coronary sinus with intact interatrial septum. PMID- 7875708 TI - Right lung agenesis with total anomalous pulmonary venous drainage. PMID- 7875709 TI - Left main coronary artery aneurysm. PMID- 7875710 TI - Recurrent neurocardiogenic syncope in a patient with sick sinus syndrome. PMID- 7875711 TI - Cholera vaccine: developmental strategies and problems. AB - Over a hundred years have elapsed since Vibrio cholerae, the etiological agent for the disease cholera, was discovered by Robert Koch. Ever since then serious efforts have been made to develop prophylactic measures to combat the disease without much success. Seven pandemics have so far been reported and cholera still remains a public health problem in developing countries. Several strategies have been adopted to develop vaccines against the disease and many of these vaccines have undergone field trials. During the last two decades, an enormous amount of information has accumulated regarding the organism V. cholerae, its virulence factors, including cholera toxin, and the molecular basis of its pathogenicity. In recent years, with the advent of recombinant DNA technology and major breakthroughs in molecular biology and immunology, a new dimension has been given to the design of vaccine strains. The second generation live oral vaccines will perhaps soon replace the long-used first generation parenterally administered killed whole cell vaccines which offered protection for not more than three months. All the recombinant vaccines tested so far produced adverse reactions in volunteers, although they provided varying degrees of protection upto about one year of surveillance. Parallel to the trials of live oral vaccines, combination vaccines comprising killed whole cells and purified B subunit of cholera toxin was also tried. These vaccines had minimal side-effects but the efficacy was not upto expectations. From the failure of each vaccine strain, new information had emerged and improved strategies were adopted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875712 TI - Effect of nuclear localization signal-receptor interaction on nuclear envelope associated ATPase activity. AB - The possibility that interaction of the nuclear localization signal (NLS) with its pore receptor may directly stimulate nuclear envelope-associated ATPase activity and consequently provide energy for protein translocation across the pore has been studied. ATPase activity was assayed after cross-linking of the prototype NLS peptide with its pore receptor, or after preincubation of envelopes with NLS-albumin conjugates. Neither treatment enhanced enzyme activity. A more complex series of events may be required for energy-generation at the nuclear pore. PMID- 7875713 TI - Differences in the levels of aminoacylation and contents of modified nucleotides between total tRNAs from N2- and NH4(+)-grown Azospirillum lipoferum cells. AB - Total tRNAs isolated from N2- and NH4(+)-grown Azospirillum lipoferum cells were compared with respect to amino acid acceptance, isoacceptor tRNA species levels and extent of nucleotide modifications. Amino-acylation of these two tRNA preparations with ten different amino acids indicated differences in the relative acceptor activities. Comparison of aminoacyl-tRNA patterns by RPC-5 column chromatography revealed no qualitative differences in the elution profiles. However, quantitative differences in the relative amounts of some isoacceptors were observed. These results indicate that alterations of relative amounts of functional tRNA species occur to match cellular requirements of the bacterial cells using N2 or NH4+ as nitrogen source. In addition, the content of modified nucleotides in total tRNAs of N2- and NH4(+)-grown cells was determined. In the NH4(+)-grown cells, content of most of the modified nucleotides decreased significantly. Based upon these results, the relationship of chargeability of tRNAs to base modifications is discussed. PMID- 7875714 TI - Different sites of photodamage in chilling-sensitive (sorghum) and chilling resistant (barley and wheat) plants. AB - The electron transport chain was affected to varying degrees by high light intensity at low temperature in different crop plants. The PS II was found to be the sensitive site while PS I showed very little change in its activity. Photoinhibition affected the oxidizing side of PS II in all three plants. However, the site of inhibition was different in chilling-sensitive and chilling resistant plants. In sorghum, the water splitting reaction was damaged while in barley and wheat the damage occurred in the reaction centre itself. It appears that photoinhibition may affect different sites within the PS II in chilling resistant and sensitive plants. PMID- 7875715 TI - Inhibition of two HMP shunt pathway enzymes by fatty acids and their CoA esters in developing human brain: role of fatty acid binding protein. AB - Inhibitory effects of fatty acids and their CoA esters on glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities of human fetal brain cytosol have been studied. Purified human fetal brain fatty acid binding protein reverses the inhibitory effects of palmitoyl-CoA and oleic acid on glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities in human fetal brain cytosol. This protein, when added alone, activates the enzymes. Levels of fatty acid binding proteins as well as the activities of these two HMP shunt pathway enzymes, which provide cofactors like NADPH for reductive biosynthesis, increase with gestation. These results indicate that a relationship exists between the high demand for fatty acids and synthesis of cofactors for lipid biosynthesis in developing brain. PMID- 7875716 TI - Folylpolyglutamate synthetase in Lactobacillus leichmannii: in vitro synthesis and characterization of polyglutamylfolates. AB - In vitro synthesis of folylpolyglutamates by folylpolyglutamate synthetase from Lactobacillus leichmannii has been studied and optimal conditions for enzyme activity determined. It is found that while ATP (5 mM) is essential for the synthesis of folylpolyglutamates homocysteine augments the same. Replacement of vitamin B12 (2 ng/ml) with deoxyuridine (20 micrograms/ml) in growth medium does not alter the enzymatic parameters studied. DEAE-cellulose column chromatography of in vitro synthesised folylpolyglutamates indicates that folylpolyglutamate synthetase of L. leichmannii can synthesize polyglutamates up to a chain length of four glutamate residues. PMID- 7875717 TI - Correlation between phospholipid biosynthesis and intracellular levels of cyclic adenosine monophosphate in Mycobacterium smegmatis. AB - The influence of intracellular levels of cAMP on phospholipid synthesis in Mycobacterium smegmatis has been examined under conditions of varying carbon source. A decreased phospholipid content was observed in glucose-grown cells, possibly due to decrease in intracellular cAMP levels caused by decreased/increased activity of adenylate cyclase and phosphodiesterase, respectively. The lowered phospholipid content was supported by decrease both in [14C]acetate incorporation and activities of key enzymes of phospholipid biosynthesis. These results in the light of our earlier observation of enhanced phospholipid synthesis in presence of increased levels of cAMP suggest a direct correlation between phospholipid biosynthesis and intracellular levels of cAMP in M. smegmatis. PMID- 7875718 TI - Increased glutathione cycling and vitamin E of P. falciparum infected erythrocytes fail to prevent spontaneous haemolysis. AB - In an attempt to understand the pathogenesis of anaemia in Plasmodium falciparum infection, the status of erythrocyte glutathione and vitamin E content in relation to the susceptibility of infected red cells to peroxide haemolysis was examined. Synchronized cultures of the parasite with either ring-, trophozoite or schizont-infected red cells showed a gradual increase in the reduced glutathione content which was significantly higher (p < 0.05) in schizont-infected cells. Trophozoite-infected cells revealed significant increase in oxidized glutathione (p < 0.01) suggesting an increase in glutathione utilization during active erythrocytic schizogony of the parasites. The membrane antioxidant vitamin E also showed an increased accumulation in trophozoite- and schizont-infected red cells (p < 0.05) but not in the uninfected or ring-infected erythrocytes. Despite a favourable change in these antioxidants, the infected as well as uninfected red cells from parasite cultures showed enhanced peroxide haemolysis (uninfected, p < 0.05; ring-rich, p < 0.05, trophozoite- and schizont-rich, p < 0.001). The study provided direct evidence for enhanced susceptibility of red cells to lysis, including those of uninfected cells exposed to parasite products. This might explain the cause for much higher red cell loss and anaemia during P. falciparum infection than all the infected cells put together. PMID- 7875719 TI - Autoimmune-like activity of sperm specific LDH: a pathophysiological and electron microscopic study of atrophied testis and epididymis. AB - Hyper-immunization of male mice with human LDH-C4 evoked autoimmune reactions illustrated by the loss of LDH activity, associated histopathological changes in testes and epididymis and induction of sterility in mice. This was substantiated by the altered morphology of sperm mitochondria and plasma membrane, and by reduced number of cytoplasmic droplets as observed by electron microscopy. However, the presence of lymphoblasts and other lymphoid cells in testes indicated that the testicular damage is accentuated by activated T lymphocytes. It is concluded that immunization with human LDH-C4 produces lesions in mouse testis and epididymis, which are similar to experimentally induced autoimmune orchitis. PMID- 7875720 TI - Kinetics of hydrolysis of sucrose catalyzed by invertase immobilized on egg shells and on zeolites. AB - A simple, inexpensive and reliable method for immobilizing yeast invertase on egg shells and on zeolites was developed. The activity of the immobilized preparations when compared with that of native enzyme at varying pH, temperature and substrate concentrations, showed improved stability and sigmoidal kinetic behaviour. The immobilized enzyme could be easily removed from the reaction mixture at any specified time. PMID- 7875721 TI - A simple in vitro method to detect singlet oxygen and to compare photodynamic activity using alkaline phosphatase. AB - A simple, sensitive and reliable in vitro method based on photodynamic inactivation of alkaline phosphatase to detect singlet oxygen and for evaluating relative photosensitizing efficiencies of photosensitizers such as hematoporphyrin (Hp) and phthalocyanines has been developed and compared with photobleaching of p-nitroso dimethyl aniline (RNO) and photooxidation of L tryptophan. Inactivation of alkaline phosphatase is dependent both on light fluence and sensitizer concentration. Scavengers like mannitol and azide anion indicated the involvement of singlet oxygen in the deactivation of alkaline phosphatase, since azide anion provided concentration dependent protection whereas mannitol had no effect and that compared to ordinary water, photoinactivation of alkaline phosphatase was three times higher in 65% D2O. Alkaline phosphatase appears to be resistant to free radical attack (particularly to OH radicals) since hydrogen peroxide alone or in presence of ferrous ions did not reduce the enzyme activity and mannitol or azide anion gave no significant protection when alkaline phosphatase was irradiated with Co-60 gamma rays up to 2 K Gy. With the present method using red light, the chloroaluminium phthalocyanine sulphonates prepared by sulphonation showed higher and the corresponding condensation product lower photodynamic activity; Hp being intermediate and Mn- and Gd-phthalocyanines had no photodynamic activity. PMID- 7875722 TI - Study of structure-activity relationships for neurotransmitters using molecular electric field mapping: histamine and some of its H2-receptor agonists. AB - Molecular electric field mapping has been carried out to study structure-activity relationships for neutral and cationic forms of histamine and some of its agonists which are thiazole derivatives. Optimised geometries and Mulliken charges at the atomic sites were obtained using the PM3 method. Electric field values near the N3-H bond in histamine and those near substituents at the C2 position in the agonists have been found to correlate reasonably well with observed activities. Electric fields near the sulphur atom in thiazoles indicate that involvement of this site in hydrogen bonding with the H2-receptor is unlikely. PMID- 7875723 TI - Nutrition, dietary fat and breast cancer--a review. PMID- 7875724 TI - Marginal resection of the mandible in oral cancer. AB - Preservation of mandible in selected cases of oral cancer provides good quality of life following surgery. The present paper based on 37 cases discusses the indications, surgical techniques and results of marginal resection of mandible. It was feasible to carry out conservation surgery even in advanced lesions (31 of 37 had stage III and IV lesion). It could be carried out in lesions close to or those clinically seem to involve the bone provided there was negative radiology. Marginal mandibulectomy could be combined with mandibulotomy in selected cases to achieve additional soft tissue clearance and better exposure. Twenty two (59%) patients were surviving disease free after such surgery for follow ups ranging 2 5 years. PMID- 7875725 TI - Nd-YAG laser therapy for palliation of obstructed colorectal carcinomas. AB - Twenty three cases of colorectal carcinoma with partial or complete obstruction were managed by laser ablation of tumour tissue. There were 14 males and 9 females with a mean age of 63 years (30-87). Nineteen cases (82.6%) were in the rectosigmoid while two cases each were in the anal canal and descending colon. Fifteen (65.2%) were proliferative growths and the remaining (8, 34.7%) were circumferential growths. Prior dilatation under fluoroscopic control was done where required. Lumen was achieved in a single sitting in 14 (60.8%) cases, while in the others two to five sittings were required. None of the patients required colostomy. Thirteen (56.5%) of these patients have died during the follow up period, lasting from 4 to 27 months (mean 10.4 months). There were no major complications related to the procedure. PMID- 7875726 TI - Speech evaluation after near total laryngectomy and total laryngectomy--a comparative acoustic analysis. AB - The practice of Pearson's (1981) technique of near total laryngectomy with speech shunt is evaluated acoustically in 11 subjects using matched esophageal speakers. Not only do these patients vocalize earlier with effortless cease, analysis of their speech both subjectively & by acoustic analysis of the parameters seems definitely to be of superior quality. The functional utility of this technique is addressed in this study justifying its more frequent practice in unilateral lesions of larynx and hypopharynx which defy satisfactory control by conventional conservation laryngeal surgery or radiation therapy. The Oncological outcome will be taken up as a part of a future report when follow up of adequate duration occurs in sufficient number of cases. PMID- 7875727 TI - Primary germ cell tumours of the mediastinum. AB - Twenty nine cases of primary mediastinal germ cell tumours (MGCT) were seen at the Tata Memorial Hospital over a 16--year period (1974-1989). There were 5 benign MGCT occurring predominantly in females (80%), with these patients having an excellent result after surgery with all patients disease free at an median follow-up of 27 months. Malignant MGCT occurred only in males and demonstrated wide variation in response to treatment depending upon whether the tumour was seminomatous or non-seminomatous. There were 11 Seminomas, 5 Embryonal carcinomas, 5 Endodermal sinus tumours and 3 Teratocarcinomas. The diagnosis was established by surgical exploration or by biopsy of a lymph node or chest wall nodule in 20 patients. Four patients had needle biopsy. Seminomatous MGCT received radiotherapy as their main treatment modality and did well with 75% of the patients alive without disease at an average follow up of 33 months. The non seminomatous MGCT could be divided into two groups. The mean survival for patients receiving cisplatinum based chemotherapy was 14 months as compared to the group not receiving such therapy where the survival was only 5.3 months. However, because of the advanced disease at presentation even in the group receiving cisplatinum chemotherapy, a long term complete response rate of only 20% could be achieved. PMID- 7875728 TI - Secondary involvement of femur in carcinoma of gall bladder. AB - A case with bony metastasis to right femur from a primary carcinoma of gall bladder is described. This is probably one of the most rare presentation of the disease without producing any signs or symptoms suggestive of a primary pathology in gall bladder. PMID- 7875729 TI - Papillary cystic neoplasm of the pancreas, diagnosed by fine needle aspiration cytology--a case report. AB - A case of papillary cystic neoplasm of the pancreas diagnosed by fine needle aspiration cytology is presented surgical removal of the pancreatic tumour and histological study confirmed the cytologic diagnosis. A brief review of the literature and emphasis on cytological and histological features are discussed. PMID- 7875730 TI - A case of spindle cell haemangioendothelioma. AB - Spindle cell haemangioendothelioma (SCH) is a low grade, slowly progressive angiosarcoma of multifocal nature with local recurrences being common. It is histologically marked by cavernous blood spaces and a spindle cell stroma. Its importance lies in recognising its relatively benign nature and differentiating it from the ominous Kaposi's sarcoma. Our case reiterates the characteristics of this recently described disease, probably the first reported from India. PMID- 7875731 TI - Murine B-cell activation via CD38 and protein tyrosine phosphorylation. AB - CD38 has been implicated in the regulation of both proliferation and rescue from apoptosis of B cells. The signalling events associated with CD38-mediated activation of murine B cells are, as yet, not well defined but it is clear that ligation of CD38 by a mitogenic antibody, NIMR-5, induces a calcium influx in resting B cells. Interestingly, however, cross-linking of CD38 does not mobilize intracellular stores of calcium. We now provide a rationale for these findings by demonstrating that CD38 is not coupled to the generation of inositol phosphates in resting B cells. We do, however, show that CD38 ligation stimulates one, or more, protein tyrosine kinase activities which may play a central role in the transduction of CD38-mediated signals leading to B-cell activation. PMID- 7875732 TI - A novel multi-gene family of sheep gamma delta T cells. AB - The WC1 protein is a cell surface constituent of bovine gamma delta T cells and is absent from most or all CD4+, CD8+ T cells and from B cells. It is a single polypeptide chain of 1413 amino acids consisting of 11 non-identical repeats of a 110 amino acid consensus sequence, homologous to the macrophage scavenger receptor cysteine rich (SRCR) domain. A 1059 nucleotide segment of the bovine WC1 cDNA sequence was used as a probe to molecularly clone homologous DNA segments from a sheep genomic library in which the presence of numerous positive plaques was documented. The high representation of such recombinants (1-2/1000 clones) within the library suggested the existence of multiple genes for WC1 (called T19 in sheep) and supported Southern blotting data which revealed an unexpectedly high number of WC1/T19 restriction fragments in sheep genomic DNA. Restriction digests of 27 samples of T19 genomic recombinants were examined by electrophoresis and Southern blotting. All but two pairs of recombinants exhibited non-overlapping restriction digest patterns. Four recombinant DNA samples were partially sequenced and in all cases putative exons were identified and exhibited high homology to appropriate segments of the WC1 cDNA at the levels of both nucleotide and amino acid sequence. Furthermore, multiple nucleotide and amino acid differences occurred between all sequences compared, establishing the existence of a repertoire of non-identical T19 genes, each with the potential to encode a different protein. PMID- 7875733 TI - Evidence that gamma delta T cells play a limited role in resistance to murine listeriosis. AB - A role for alpha beta and gamma delta T cells in protection against primary and secondary infection with Listeria monocytogenes was studied. The results show that mice depleted of either gamma delta T cells with 3A10 monoclonal antibody (mAb), or alpha beta T cells with anti-CD4 plus anti-CD8 mAb, or both types of T cells, remained capable of controlling Listeria multiplication during the first 4 days of primary sublethal infection. Moreover, mice depleted of either or both types of T cells also remained capable of resolving primary infection, although the absence of alpha beta T cells, but not gamma delta T cells, caused resolution to be slower. Likewise, Listeria-immune mice depleted of either alpha beta or gamma delta T cells remained capable of resolving secondary infection with a large inoculum of L. monocytogenes, although depletion of alpha beta T cells, and to a much lesser extent gamma delta T cells, resulted in early exacerbation of infection. However, immune mice depleted of both types of T cells lost their ability to resist a lethal Listeria challenge. Taken together, the results show that whereas neither type of T cell is needed for resistance to sublethal primary listeriosis, alpha beta T cells may act in concert with gamma delta T cells in protecting mice against lethal secondary infection. In addition, the results indicate that the role of gamma delta T cells in anti-Listeria resistance is much less important than the role of alpha beta T cells, and can be demonstrated mainly in the absence of alpha beta T cells. PMID- 7875735 TI - Influence of the lpr environment on the lymph node cell phenotypes in C57BL/6 nubg and nulpr chimeras. AB - Mice homozygous for the lpr gene show a marked lymphoproliferative syndrome. Most T cells which accumulate in their lymphoid organs belong to a fairly unusual subpopulation. Although being CD44+ T cells expressing neither CD4 nor CD8, they are CD3 T-cell receptor (TCR) alpha beta positive and express both Thy-1 and B220, the B-cell form of the CD45 marker. To support engraftment and development of transferred lpr lymphomyeloid cells, athymic recipients must be genetically lpr. While nude/beige (nubg) recipients do not allow the development of any lymphoproliferative syndrome, this is variable in nude/lpr (nulpr) recipients, and the genotypic origin of the proliferating lymphocytes in nulpr recipients is unclear. In this study, the surface phenotype of lymph node cells from nulpr recipients of lpr grafts ([lpr-->nulpr] chimeras) was analysed by flow cytometry, and compared with various chimeras and parental (donor and recipient) strains as controls. Abnormal cells of the lpr type were not detectable either in [lpr- >nubg] chimeras or in [wild-->nubg] controls. Absence of lpr cells was also seen in neonatal lpr thymus-grafted nubg mice engrafted previously with lpr haematopoietic cells. In contrast, a substantial emergence of double-positive B220+ Thy-1+ cells occurred in [lpr-->nulpr] chimeras, together with high levels of CD4+ cells, a substantial fraction of which might express B220. Finally, in thymus-grafted nulpr mice, the levels of B220+ Thy-1+ cells were as high as in lpr mice and there was again an expansion of CD4+ (potentially B220+) cells. Abnormality of the nulpr haemopoietic environment was also shown by the low percentages of T cells, particularly CD8+ cells, in short-lived [wild-->nulpr] chimeras. Taken together, our results underline the differences between the nubg and nulpr environments. PMID- 7875734 TI - T-cell receptor V beta repertoire of L3T4+ regulatory T cells in anti-L3T4 antibody-induced tolerant NOD mice. AB - In ongoing studies, we have found that short-term administration of anti-L3T4 monoclonal antibodies (mAb) prevents the development of overt diabetes in non obese diabetic (NOD) mice. In the present work, we asked whether L3T4+ T cells or Lyt-2+ T cells can suppress the diabetes in these mice. L3T4+ T cells or Lyt-2+ T cells were sorted using a magnetic cell sorter, then were transferred into cyclophosphamide-induced male NOD mice. We obtained evidence that the L3T4+ but not Lyt-2+ T cells did inhibit the diabetes, thereby indicating that the former can regulate diabetes in anti-L3T4 mAb-induced tolerant NOD mice. Further analysis on T-cell receptor (TCR) V beta genes on splenic T cells from anti-L3T4 mAb-treated NOD mice revealed that V beta 4-positive T cells expanded predominantly, while L3T4+ T cells represented heterogeneity of the TCR V beta gene, hence, V beta 4-positive Lyt-2+ T cells generate predominantly. Our findings suggest that both L3T4+ and Lyt-2+ T cells renew and function as regulatory cells, through clonotypic interaction in tolerant NOD mice. PMID- 7875736 TI - Failure of SCID mice to generate an oral tolerogen after a feed of ovalbumin: a role for a functioning gut-associated lymphoid system. AB - The role of the mucosal immune system in the generation of circulating tolerogenic ovalbumin (OVA) moieties has been investigated after a single feed of the protein. Serum collected from SCID mice 1 hr after a 25-mg feed of OVA was unable to transfer tolerance of delayed-type hypersensitivity (DTH) into naive BALB/c recipients. This is in contrast to serum collected from BALB/c mice which was able to transfer DTH tolerance to naive BALB/c recipients. The levels of circulating OVA detected in the serum of SCID mice 60 min after feeding OVA were approximately half those detected in the serum of BALB/c mice at the same time point. However even dose adjustment of SCID mouse serum to a level of immunoreactive OVA equivalent to that found in BALB/c serum was unable to induce DTH tolerance in BALB/c recipients. This failure of SCID serum to transfer tolerance was shown to be unrelated to the germ-free conditions under which SCID mice are kept. Serum from OVA-fed germ-free BALB/c mice transferred DTH tolerance at equivalent levels to serum from conventionally reared BALB/c mice. When the intestinal morphology and intraepithelial lymphocyte (IEL) numbers in the duodenum of SCID mice were compared to conventionally reared and germ-free BALB/c controls, SCID mice were characterized by a lower number of IEL with a different morphology from the majority of IEL found in BALB/c mice. PMID- 7875737 TI - Langerhans' cell depletion by staphylococcal superantigens. AB - Superantigens were examined for effects on the distribution of Langerhans' cells (LC) in mouse skin. This was accomplished by analysing the expression of LC specific markers, ATPase and IA among the epidermal portion of cultured sections of mouse skin following treatment with staphylococcal enterotoxins. In this study, treatment of skin sections with staphylococcal enterotoxin A or exfoliative toxin but not toxic shock syndrome toxin led to significant depletion of LC. This depletion was inhibited by agents which specifically block the action of GTP binding proteins or their associated kinases (cholera and pertussis toxins and H-8) as well as those which block protein or RNA synthesis. Therefore, signals which lead to LC depletion in response to staphylococcal enterotoxins appear to involve a cholera and pertussis toxin-sensitive GTP-binding protein and protein synthesis. These requirements are identical to those observed previously for LC depletion following exposure of skin to ultraviolet radiation. PMID- 7875739 TI - Inhibition of expression of delayed hypersensitivity by neutralizing monoclonal anti-T-cell fibronectin antibody. AB - T-cell fibronectin (FN) is a unique cellular FN that is rapidly synthesized by memory T cells in response to antigen. Monoclonal anti-T-cell FN antibodies have been used to clarify the role of T-cell FN in the in vivo expression of delayed hypersensitivity. IgGl(kappa) mouse anti-human T-cell FN monoclonal antibodies 231 and 248 recognized epitopes on the FN cell-binding domain, were cross reactive with plasma FN, and neutralized human and guinea-pig T-cell FN monocyte agglutinating activity. When injected intradermally together with tuberculin or 30 min before topical application of reactive sensitizer, antibody 231 significantly decreased macroscopic expression of guinea-pig delayed hypersensitivity at 24 hr in a dose-dependent manner. Similar doses of antibody 248 caused a slight statistically non-significant enhancement of delayed-type hypersensitivity (DTH) expression. Inhibition of visible skin responses was not associated with qualitative or quantitative changes in cellular infiltrates at the reaction site. Antibody 231 modulated expression of delayed hypersensitivity in a qualitatively and quantitatively similar manner to the FN-binding mycobacterial antigen 85 proteins. This is consistent with anti-T-cell FN and antigen 85 acting on the same molecule in vivo. PMID- 7875738 TI - Characterization of CMRF-44, a novel monoclonal antibody to an activation antigen expressed by the allostimulatory cells within peripheral blood, including dendritic cells. AB - Dendritic cells (DC) are the most potent antigen-presenting cells (APC) involved in the initiation of primary T-lymphocyte responses. However, despite their importance, no DC-specific surface marker has been identified in humans and many aspects of their ontogeny and the mechanisms underlying their potent functional activity remain unknown. In this report we describe a novel monoclonal antibody (mAb), CMRF-44, which recognizes an early activation antigen expressed by human DC and acts as a marker of allostimulatory activity within preparations of peripheral blood mononuclear cells (PBMC). The CMRF-44 antigen was expressed strongly on DC isolated from blood and tonsil by standard techniques, but was not detectable on Langerhans' cells within skin or on DC isolated directly from blood using a cell-sorting method which involves minimal DC manipulation/activation. Normal resting peripheral blood leucocytes did not label with CMRF-44, although weak staining of a small subpopulation (15%) of blood B lymphocytes was identified by double labelling. However, following overnight culture at 37 degrees, moderate staining of a subpopulation of PBMC was detected. Confirmation that CMRF-44 recognized an early marker of activated DC and hence allostimulatory activity was obtained by sorting cultured cell preparations on the basis of CMRF 44 reactivity. A marked enrichment of allostimulatory activity was observed in the CMRF-44-positive cellular population, whereas the CMRF-44-negative cells showed only minimal stimulatory activity. Activation studies established that the CMRF-44 antigen was an early activation marker, expressed constitutively on the majority of tonsil B lymphocytes, which can be induced on peripheral blood B lymphocytes and subpopulations of monocytes. Expression of the CMRF-44 antigen on cell lines was similarly restricted, CMRF-44 antigen being detected only on Hodgkin's disease-derived and B-lymphoid lines. The cellular distribution, expression kinetics and biochemical characteristics of the CMRF-44 antigen identify it as a new early marker of activated allostimulatory (DC) populations. PMID- 7875740 TI - Identification of three distinct allelic forms of bovine CD4. AB - The CD4-specific monoclonal antibody (mAb) CC26, when tested on a total of 143 cattle, failed to react with T cells from 16% of animals and gave reduced intensity staining in a further 35% of animals. The results of family studies with groups of half- and full-siblings indicated that CC26 recognizes an allele of CD4 which is co-dominantly expressed in heterozygous animals. This was confirmed by sequential immunoprecipitation and by selecting transfectants expressing the CC26+ and CC26- allelic forms of CD4 following transfection of genomic DNA from a heterozygous animal. Biochemical studies also revealed an allelic difference in the relative molecular weight (M(r)) of the CD4 molecule, one allele giving 49,000/52,000 MW bands and the other 52,000/57,000 MW bands in sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Treatment of CD4+ cell lines with tunicamycin resulted in the appearance of a 47,000 MW band for both allelic forms indicating that the difference in M(r) is due to glycosylation. All of the CC26+ alleles examined were of the low molecular weight form (M(r)low) whereas both M(r)low and M(r)high alleles were represented in CC26 animals. Thus, on the basis of M(r) and reactivity with mAb CC26, three allelic forms of bovine CD4 can be identified, namely CC26+ M(r)low, CC26- M(r)low and CC26- M(r)high; it is proposed that these alleles are designated CD4.1, CD4.2 and CD4.3, respectively. The allelic difference detected by CC26 was present in both Bos taurus and B. indicus cattle indicating that it had arisen prior to divergence of these subspecies. The M(r)high allele (CD4.3) was detected only in B. indicus animals. PMID- 7875741 TI - Differential effects of chlorination of bacteria on their capacity to generate NO, TNF-alpha and IL-6 in macrophages. AB - Activated rodent macrophages produce high amounts of nitric oxide (NO). NO as a tumoricidal and defence molecule against intracellular parasites is commonly accepted. However, its role as an obligatory killing factor for extracellular bacteria is controversial. In the present study we stimulated murine peritoneal macrophages by heat-killed bacteria (Staphylococcus aureus, S. epidermidis and Escherichia coli). In some groups bacteria were pretreated with HOCl, to replace the chlorinating system in activated neutrophils that operates as a bactericidal system in vivo. High levels of NO, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were detected after stimulation by all non-chlorinated bacteria strains tested. However, after chlorination Gram-positive bacteria lost their ability to induce NO and TNF-alpha, whereas phagocytosis and IL-6 production were not affected by chlorination. PMID- 7875742 TI - Role of neutrophil Fc gamma RIIa (CD32) and Fc gamma RIIIb (CD16) polymorphic forms in phagocytosis of human IgG1- and IgG3-opsonized bacteria and erythrocytes. AB - The four subclasses of IgG have different biological activities associated with their Fc regions. Fc gamma receptors on leucocytes (Fc gamma R) mediate binding and phagocytosis of opsonized particles. Two structurally and functionally distinct allelic polymorphisms of the Fc gamma R have been defined: the H/R131 forms of Fc gamma RIIa (CD32), and the neutrophil antigen 1 (NA1)/NA2 forms of Fc gamma RIIIb (CD16). In this study the activities of allotypes of CD16 are analysed with antibacterial IgG subclass antibodies and with IgG1 and IgG3 anti Rhesus D, and the activities of CD32 with IgG1 and IgG3 anti-Rhesus D. With respect to the allotypes of CD16, polymorphonuclear leucocytes (PMN) homozygous for Fc gamma RIIb-NA2 exhibited a lower (21-25%) IgG1-mediated phagocytosis of Staphylococcus aureus strain Wood (STAW), Haemophilus influenzae type b (Hib), and Neisseria meningitidis group B (NMen) than IIIb-NA1 PMN. The difference was apparent only when the micro-organisms were opsonized in the absence of complement, and was furthermore enhanced (34-52%) upon blockade of Fc gamma RIIa. In addition, monoclonal IgG3 anti-D-mediated rosette formation and phagocytosis was consistently found to be lower (16%) with Fc gamma RIIIb-NA2 than with IIIb NA1 PMN. For the allotypes of CD32 we now show that IgG3 anti-D sensitized erythrocytes formed more (50%) rosettes and were phagocytosed at a higher rate with PMN carrying Fc gamma RIIa-H131 than with PMN carrying IIa-R131. Heterozygous Fc gamma RIIa-H/R131 PMN exhibited intermediate phagocytic activity in this respect. This study illustrates a critical role of Fc gamma R allotypes in functional interactions with biologically relevant IgG subclass antibodies. PMID- 7875743 TI - Studies of protein A and herpes simplex virus-1 induced Fc gamma-binding specificities. Different binding patterns for IgG3 from Caucasian and Oriental subjects. AB - Herpes simplex virus type 1 (HSV-1) expresses a receptor that binds the Fc portion of IgG. This HSV-1 Fc gamma-binding protein is, like protein A of Staphylococcus aureus, known to bind human IgG1, IgG2 and IgG4 but not IgG3 subclasses. However, IgG3 with the allotype Gm(s+)(t+), prominent in the Oriental population, reacts with protein A. This prompted us to investigate the reactivity of Oriental IgG3 monoclonal myeloma proteins of various allotypes with the HSV-1 Fc gamma-binding protein. Of seven Oriental IgG3 myeloma proteins with allotypes Gm(s+)(t+)(u-)(b+)(g-), Gm(s-)(t-)(u+)(b+)(g-) and Gm(s-)(t-)(u+)(b-)(g+), all reacted with the HSV-1 Fc gamma-binding protein. This was in contrast to negative reactions obtained with three IgG3 myeloma proteins of Caucasian origin with Gm(b+)(g-) or Gm(b-)(g+) phenotypes. The same binding pattern, i.e. binding of IgG3 of Oriental but not of Caucasian origin, was found with protein A. The binding of the monoclonal Oriental IgG3 proteins was again independent of the G3m phenotype. These findings support the concept that the HSV-1 Fc gamma-binding protein A have a similar binding site on the IgG molecule. All monoclonal IgG3 proteins derived from Oriental subjects with or without histidine at position 435 bound to HSV Fc gamma-binding protein. This suggests that Oriental IgG3 myeloma proteins with Gm(s-)(t-) phenotypes have additional critical amino acid residue substitutions important for HSV Fc gamma binding different from those already known. PMID- 7875744 TI - Regulation of DTH and IgE responses by IL-4 and IFN-gamma in immunized mice given pertussis toxin. AB - Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) are cytokines with important functions in regulating immune responses. IFN-gamma may be produced by cells responsible for delayed-type hypersensitivity (DTH), whereas IL-4 is essential for IgE production. Pertussis toxin (PT) from Bordetella pertussis enhances both DTH and IgE responses, and causes enhancement of both IFN-gamma and IL-4 secretion in immunized mice. In the present study, the effects of neutralizing monoclonal antibodies against IFN-gamma or IL-4 on DTH, serum IgE and cytokine production were assessed. Treatment with a monoclonal anti-IL-4 antibody at the time of immunization caused a striking increase in DTH responses, and elicited enhanced IFN-gamma expression, while inhibition of the production of IL-4 and IgE was observed. By contrast, injection of a monoclonal anti-IFN-gamma antibody was followed by significant but not complete suppression of DTH reactions. IFN-gamma secretion was also inhibited, whereas IL-4 production and serum IgE were increased. Thus antibodies to IL-4 and IFN-gamma, given at the time of immunization, can profoundly influence the nature of short-term immune responses elicited by PT in immunized mice. PMID- 7875745 TI - Effect of IFN-gamma on the proliferation of Toxoplasma gondii in monocytes and monocyte-derived macrophages from AIDS patients. AB - This study was undertaken to determine whether the activity of monocytes and monocyte-derived macrophages (MDM) from acquired immune deficiency syndrome (AIDS) patients against Toxoplasma gondii is altered and whether this activity can be modulated by recombinant interferon-gamma (rIFN-gamma). Untreated and rIFN gamma-treated monocytes or MDM from AIDS patients and from healthy controls were infected with T. gondii and the proliferation of these protozoa was determined. The H2O2 release by monocytes from AIDS patients and healthy controls was measured upon stimulation with phorbol myristate acetate (PMA) and formyl methionyl leucyl phenylalanine (FMLP). Monocytes from AIDS patients exhibited significantly lower toxoplasmastic activity compared to monocytes from healthy controls. The H2O2 release by monocytes from AIDS patients was also diminished. Incubation of monocytes from AIDS patients with rIFN-gamma for 2 days, but not 1 day, restored their toxoplasmastatic activity. The rate of proliferation of T. gondii was higher in MDM from AIDS patients than in MDM from healthy controls. Treatment of MDM from AIDS patients with rIFN-gamma for 1, 2 or 3 days resulted in partial inhibition of the proliferation of T. gondii. Collectively, these results demonstrate that the reduced toxoplasmastatic activity of monocytes and MDM from AIDS patients can be enhanced by in vitro treatment with rIFN-gamma, which supports the clinical use of rIFN-gamma for the treatment of opportunistic infections in these patients. PMID- 7875746 TI - Recombinant L7/L12 ribosomal protein and gamma-irradiated Brucella abortus induce a T-helper 1 subset response from murine CD4+ T cells. AB - Immunity to Brucella abortus crucially depends on antigen (Ag)-specific T-cell mediated activation of macrophages, which are the major effectors of cell mediated killing of this organism. Ribosomal preparations have been used as vaccines against several pathogens, including B. abortus, conferring a high degree of protection. In the present study, we have examined the pattern of T helper (Th) cell response from infected BALB/c mice after in vitro stimulation with recombinant (r) L7/L12 ribosomal protein or gamma-irradiated B. abortus. In addition to Ag-specific proliferation, CD4+ T cells were tested for interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma) mRNA expression and secretion. Detection of cytokine transcripts and secreted cytokines was performed using reverse transcriptase (RT)-polymerase chain reaction (PCR) and specific ELISA assays. Primed CD4+ T cells proliferated to the recombinant protein or whole B. abortus. The functional cytokine profile of the proliferating cells was typical of a Th1 cell phenotype, as we detected transcripts for IL-2 and IFN-gamma but not IL-4. Among the cytokines analysed, only IFN-gamma produced in the Th cell culture supernatants was detected by ELISA when bacteria or recombinant protein were used. Thus, rL7/L12 ribosomal protein and gamma-irradiated B. abortus preferentially stimulated IFN-gamma-producing Th1 cells after in vitro stimulation. The results of this study provide for the first time an explanation of why ribosomal vaccines may protect against intracellular infections, and an experimental basis for identifying polypeptides from a pathogen which stimulates the desired cytokine profile and Th cell response crucial for the design of genetically engineered candidate vaccines. PMID- 7875747 TI - Antigen expressed by Salmonella typhimurium is processed for class I major histocompatibility complex presentation by macrophages but not infected epithelial cells. AB - Macrophages were shown to mediate class I major histocompatibility complex (MHC 1) presentation of a fusion protein (Crl-OVA) expressed in Salmonella typhimurium, a bacterium which fails to escape from vacuolar compartments after phagocytosis or penetration into host cells. Salmonella typhimurium also penetrates into non-phagocytic intestinal epithelial cells, a portal of entry for systemic infection. We tested the ability of infected epithelial cells to process antigen expressed by S. typhimurium for presentation by MHC-I molecules to CD8+ T cells. CMT-93 murine adenocarcinoma cells expressed Kb and effectively presented the OVA 257-264 peptide to CD8 OVA T-hybridoma cells, but infected CMT-93 cells failed to process Crl-OVA expressed in S. typhimurium. Therapeutically useful MHC I-restricted cytotoxic T-lymphocyte (CTL) responses may be generated by macrophage presentation of Salmonella antigens or recombinant antigens expressed in Salmonella vaccine vectors. Our data suggest that an inability of epithelial cells to present these antigens may limit the utility of CTL in epithelial immunity in salmonellosis, but studies of additional epithelial cell systems are needed. PMID- 7875749 TI - Evaluation of diclofenac sodium as a perioperative analgesic. AB - 1. This study was undertaken to assess whether the analgesia conferred by Diclofenac sodium in the post operative period following general surgery is enhanced by preoperative administration of the drug. 2. Two groups of patients were studied. Group I patients received narcotic premedication and Group II patients received Diclofenac sodium as premedication. Post operatively both groups were administered intramuscular Diclofenac sodium 8 hourly for 48 hours. 3. Pain scoring using visual analogue scale indicated a better pain relief in Group II patients. In Group I, 75% patients had a pain score less than 3 whereas 85% in Group II had a pain score less than 3 (Figure 1). 4. Pulmonary function tests were done 24 hours after surgery and revealed improved values of all parameters in Group II patients. This indicates a greater degree of analgesia in Group II patients. 5. Preoperative administration of the drug reduces the initiation of pain in the periphery and decreases the inflammatory response after surgery. 6. NSAIDS do not have any central effect or any respiratory depression. Patients in our study were found to be awake, cooperative and pain free. The additional analgesia conferred by preoperative administration in conjunction with adequate postoperative therapy allows us to recommend Diclofenac sodium as a sole analgesic for perioperative pain relief except in those patients with a bleeding diathesis. PMID- 7875750 TI - Teacher's knowledge and practice of breast self examination. AB - Data collected by interview of 100 teachers of schools and colleges regarding knowledge and practice of self examination of breast is analysed. Results showed that although the fear of breast cancer is common, the knowledge and practice of self examination was deficient and not regularly followed. A plea is made to publicise this in health education programmes and in media as a measure for early detection of breast cancer. PMID- 7875751 TI - Atypical case of cystic fibrosis. AB - A patient of cystic fibrosis is hereby reported. He had no family history and presented with chest symptoms, only. There was no evidence of hepatic or pancreatic involvement. To our knowledge this represents the first case of its kind from this part of country. PMID- 7875748 TI - Physical biochemical properties of IgM from a teleost fish. AB - Teleost fish are able to produce IgM class antibody, as are other vertebrates. When the teleost fish Oreochromis niloticus was immunized with bovine serum albumin (BSA), it produced antibody to BSA with an average avidity of 7.4 x 10(8)/M. Thus, dissociation of antigen-antibody complexes only occurred at conditions of < pH 2.5, > pH 11, > 4M NaI or > 4M urea, demonstrating high stability of the complex. Western blot analyses further showed the high specificity of the antibody to BSA. In contrast to mammals, when the fish was challenged with multiple protein antigens, it produced antibody only to the major component but not to others. The antibody generated to a specific antigen accounted for up to 1.1% of whole serum protein or 7.0% of whole immunoglobulin. We conclude (1) the systemic antibody response in teleost fish may be an 'all or nothing' response, which is different from that in mammals; (2) the quality (specificity and affinity) of the antibody produced is similar to that of mammals. The findings not only reveal a quite different strategy of immune response in fish, but also raise the possibility of technical application. PMID- 7875752 TI - Fagan returns NIH grant. PMID- 7875753 TI - There's good news and not so good news. PMID- 7875754 TI - Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988-1991. AB - The purpose of this study was to estimate the current prevalence and distribution of hypertension and to determine the status of hypertension awareness, treatment, and control in the US adult population. The study used a cross-sectional survey of the civilian, noninstitutionalized population of the United States, including an in-home interview and a clinic examination, each of which included measurement of blood pressure. Data for 9901 participants 18 years of age and older from phase 1 of the third National Health and Nutrition Examination Survey, collected from 1988 through 1991, were used. Twenty-four percent of the US adult population representing 43,186,000 persons had hypertension. The age-adjusted prevalence in the non-Hispanic black, non-Hispanic white, and Mexican American populations was 32.4%, 23.3%, and 22.6%, respectively. Overall, two thirds of the population with hypertension were aware of their diagnosis (69%), and a majority were taking prescribed medication (53%). Only one third of Mexican Americans with hypertension were being treated (35%), and only 14% achieved control in contrast to 25% and 24% of the non-Hispanic black and non-Hispanic white populations with hypertension, respectively. Almost 13 million adults classified as being normotensive reported being told on one or more occasions that they had hypertension; 51% of this group reported current adherence to lifestyle changes to control their hypertension. Hypertension continues to be a common finding in the general population. Awareness, treatment, and control of hypertension have improved substantially since the 1976-1980 National Health and Nutrition Examination Survey but continue to be suboptimal, especially in Mexican Americans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875755 TI - Antisense inhibition of hypertension in the spontaneously hypertensive rat. AB - Phosphorothioated antisense oligodeoxynucleotide (ASODN) targeted to angiotensinogen mRNA was administered intracerebroventricularly in spontaneously hypertensive rats to test whether angiotensinogen reduction would lower their hypertensive blood pressures. The ASODN lowers hypertensive blood pressures to normotensive levels in spontaneously hypertensive rats; sense oligodeoxynucleotide had no effect. Administration of phosphorothioated ASODN produced a prolonged duration of lowered blood pressure. Injections of ASODN at the same dose that decreased hypertension when administered centrally did not result in blood pressure decreases when administered intra-arterially. Furthermore, angiotensinogen production was decreased in the brain stem and significantly decreased in the hypothalamus of the ASODN-treated rats (P < .05), supporting the concept of centrally mediated regulation of hypertension by an overactive brain angiotensin system. To determine the distribution of centrally administered oligodeoxynucleotides, fluorescein isothiocyanate-conjugated oligodeoxynucleotides were injected directly into the lateral ventricles. One hour later, oligodeoxynucleotides were distributed throughout the lateral and third ventricles, with tissue and cellular uptake observed in discrete cells at the injection site. This indicates that the oligodeoxynucleotides are taken up rapidly by brain cells and that they permeate the areas surrounding brain nuclei involved in central blood pressure regulation and volume homeostasis. The results confirm and extend our previous study with phosphodiester ASODN and show that phosphorothioation modification increases the duration of the response and is taken up in vivo. We conclude that with modification, ASODN inhibition of angiotensinogen mRNA translation can be used for a prolonged, profound decrease in mean arterial pressure in the spontaneously hypertensive rat through a central mechanism. PMID- 7875756 TI - Association of the alpha-adducin locus with essential hypertension. AB - Previous studies on genetic rat hypertension have shown that polymorphism within the alpha-adducin gene may regulate blood pressure. Adducin is a cytoskeletal protein that may be involved in cellular signal transduction and interacts with other membrane-skeleton proteins that affect ion transport across the cell membrane. There is a high homology between rat and human adducin and pathophysiological similarities between the Milan hypertensive rat strain and a subgroup of patients with essential hypertension. Thus, we designed a case control study to test the possible association between the alpha-adducin locus and hypertension. One hundred ninety primary hypertensive patients were compared with 126 control subjects. All subjects were white and unrelated. Four multiallelic markers surrounding the alpha-adducin locus located in 4p16.3 were selected: D4S125 and D4S95 mapping at 680 and 20 kb centromeric, and D4S43 and D4S228/E24 mapping at 660 and 2500 kb telomeric. Alleles for each marker were pooled into groups. Comparisons between control subjects and hypertensive patients were carried out by testing the allele-disease association relative to the marker genotype. The maximal association occurred for D4S95 (chi 2(1) 13.33), which maps closest to alpha-adducin. These data suggest that a polymorphism within the alpha-adducin gene may affect blood pressure in humans. PMID- 7875757 TI - Lisinopril improves aortic compliance and renal flow. Comparison with nifedipine. AB - We compared the systemic and regional hemodynamic effects of nifedipine and lisinopril in 26 elderly hypertensive patients with the use of the pulsed Doppler ultrasound technique. Nifedipine is a dihydropyridine calcium antagonist, and lisinopril is an angiotensin-converting enzyme inhibitor. The study had a single blind crossover design: nifedipine and lisinopril were given for 8 weeks each after washout periods of 4 weeks. Both nifedipine and lisinopril significantly reduced mean arterial pressure to the same extent (P < .01); cardiac output remained unchanged in both nifedipine- and lisinopril-treated groups. Lisinopril increased renal flow significantly (P < .01), but nifedipine did not. Common carotid, vertebral, celiac, and superior mesenteric arterial and diaphragmatic and terminal aortic flows did not show a significant change with either nifedipine or lisinopril. The specific action of lisinopril on the thoracic aorta was a marked improvement of aortic compliance compared with nifedipine, which might be partly responsible for an increase in renal flow. Lisinopril may provide more desirable regional hemodynamic effects and additional benefits for elderly hypertensive patients. PMID- 7875758 TI - Enalapril does not prevent renal arterial hypertrophy in spontaneously hypertensive rats. AB - Angiotensin-converting enzyme inhibitors prevent the development of vessel wall hypertrophy in some vascular beds in spontaneously hypertensive rats (SHR), but their effects on hypertrophy of renal arterial vessels have not been studied. We therefore used stereological techniques to study wall and lumen dimensions of the interlobular (cortical radial) and arcuate arteries in the kidneys of SHR (n = 7), SHR treated from 4 to 10 weeks of age with enalapril (25 to 30 mg/kg per day; SHR-E, n = 7), and Wistar-Kyoto rats (WKY, n = 7). All kidneys were perfusion fixed at 10 weeks. Systolic blood pressure was 199 +/- 9, 139 +/- 11, and 156 +/- 8 mm Hg in the SHR, SHR-E, and WKY groups, respectively. For the interlobular arteries, the volume density of artery wall, wall-to-lumen ratio, and wall thickness in the untreated SHR were significantly greater than in the WKY (0.84 +/- 0.09 versus 0.69 +/- 0.07 x 10(-3), 0.75 +/- 0.20 versus 0.53 +/- 0.08, and 13.6 +/- 3.3 versus 10.6 +/- 0.8 microns, respectively), but values in the SHR-E were similar to those in the untreated SHR (1.10 +/- 0.20 x 10(-3), 0.88 +/- 0.22, and 14.0 +/- 2.6 microns, respectively). For the arcuate arteries, wall thickness and volume density were significantly greater in SHR than WKY (17.3 +/- 3.0 versus 13.9 +/- 1.7 microns and 1.63 +/- 0.51 versus 1.14 +/- 0.27 x 10(-3), respectively), and values in the SHR-E (15.7 +/- 1.7 microns and 1.69 +/- 0.50 x 10(-3), respectively) were not significantly different from those in SHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875759 TI - Glucocorticoids induce angiotensin-converting enzyme expression in vascular smooth muscle. AB - Angiotensin-converting enzyme (ACE) activity plays a central role in vessel growth and remodeling as shown by the fact that ACE inhibitors reduce neointimal proliferation after rat carotid injury. To investigate the mechanisms that regulate smooth muscle cell ACE expression, we studied the effects of steroids on ACE activity and mRNA in cultured rat aortic smooth muscle cells. ACE activity was present at low levels independent of growth state. In response to the glucocorticoid dexamethasone (100 nmol/L for 72 hours), ACE activity (hydrolysis of [3H]benzoyl-Phe-Ala-Pro) increased 10.1 +/- 3.1-fold. The increase in activity occurred within 12 hours and peaked after 72 hours of treatment. The increase in ACE activity was specific for glucocorticoids and paralleled their potency (dexamethasone > hydrocortisone = prednisolone). Dexamethasone increased the steady-state level of ACE mRNA in a concentration-dependent manner (21.4 +/- 0.4 fold at 100 nmol/L for 72 hours). Dexamethasone stimulation of ACE expression appeared to be due to both increased transcription and stabilization of ACE enzyme mRNA. This was suggested by the finding that dexamethasone stimulated nuclear run-on expression of ACE mRNA by only threefold, in contrast to the 21 fold increase in steady-state mRNA. These findings establish that ACE is a dynamically regulated enzyme in rat aortic smooth muscle cells. In addition, the present findings suggest an important role for stress steroids in the vascular response to injury in vivo. PMID- 7875760 TI - Enhanced Na(+)-H+ exchanger activity and NHE-1 mRNA expression in lymphocytes from patients with essential hypertension. AB - It has been demonstrated that the activity of the sodium-proton exchanger (NHE-1 isoform) is increased in lymphocytes and other blood cells from patients with essential hypertension. In the present study, we investigated whether an increased level of NHE-1-specific mRNA in lymphocytes from patients with essential hypertension would explain the enhanced transport activity. Twenty-two hypertensive patients and 21 normotensive subjects were studied. Basal cytosolic pH was measured by the pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl) 5(6)-carboxyfluorescein. Maximal sodium-proton exchange activity was determined by acidifying cell pH and measuring the initial rate of the net sodium-dependent proton efflux driven by an outward proton gradient. The transcript level of NHE-1 was measured by reverse transcription-polymerase chain reaction in comparison with a constitutively expressed reference gene (beta-actin). Intracellular pH was lower in hypertensive patients than normotensive subjects (7.34 +/- 0.01 versus 7.39 +/- 0.01, mean +/- SEM, P < .001). The maximal activity of the sodium-proton exchanger was higher in hypertensive patients than in normotensive subjects (1262 +/- 100 versus 881 +/- 56 mmol/L cells per hour, P < .01). NHE-1 mRNA was increased in hypertensive patients compared with normotensive subjects (ratio of NHE-1 mRNA to beta-actin mRNA, 0.16 +/- 0.01 versus 0.12 +/- 0.02, P < .05). These data suggest that the increased sodium-proton exchange activity in essential hypertension may be related to the de novo synthesis of exchanger protein. PMID- 7875761 TI - Modulation of the Ca2+ pump by the hypothalamic-hypophysary inhibitory factor. AB - We previously purified to homogeneity an endogenous sodium pump inhibitor from bovine hypothalamus and hypophysis that is different from digoxin or ouabain and studied the effects of this factor on the total Ca2+,Mg(2+)-ATPase activity of plasma membrane of synaptosomes. This factor inhibits the calcium pump and the total Mg(2+)-ATPase activity of these membranes with approximately the same K0.5 values of inhibition. The potency of this factor as an inhibitor depends on the membrane concentration in the assay medium. The inhibition of the magnesium dependent ATPase activities of these membranes was of a noncompetitive type with respect to the substrate Mg(2+)-ATP and did not significantly shift the calcium dependence of the Ca2+,Mg(2+)-ATPase activity. We suggest that the calcium pump of the synaptosomal plasma membrane is inhibited by this factor through disruption of the lipid annulus; this inhibition could play a role in the control of calcium homeostasis by increasing the cytosolic free calcium concentration. PMID- 7875762 TI - Brain 'ouabain' and desensitization of arterial baroreflex by high sodium in Dahl salt-sensitive rats. AB - In Dahl salt-sensitive (S) rats, high sodium intake further desensitizes arterial baroreflex function. To assess the possible involvement of brain "oubain," we gave Dahl S rats a regular or high sodium diet from 4 to 7 weeks of age and administered intracerebroventricular antibody Fab fragments, which bind ouabain with high affinity, or gamma-globulins as control (200 micrograms/12 microL per day for both) using osmotic minipumps. We assessed arterial baroreflex function by plotting changes in renal sympathetic nerve activity or heart rate against changes in mean arterial pressure of conscious rats elicited by intravenous phenylephrine and nitroprusside. Dahl S rats on high sodium treated with gamma globulins showed a significantly higher resting mean arterial pressure versus other rats (130 to 140 versus 95 to 105 mm Hg). In rats treated with gamma globulins, high sodium desensitized baroreflex control of renal sympathetic nerve activity compared with rats on regular sodium (average gain: -1.88 +/- 0.12 versus -2.73 +/- 0.13, P < .05). In contrast, in rats treated with Fab fragments, high sodium did not increase blood pressure and did not desensitize but slightly sensitized reflex control of renal sympathetic nerve activity. Changes in reflex control of heart rate were similar to those of renal sympathetic nerve activity. These data indicate that blockade of brain "oubain" prevents sodium-induced hypertension as well as the desensitization of the arterial baroreflex in Dahl S rats. Increased brain "oubain" may desensitize the arterial baroreflex and thereby facilitate the hypertension in Dahl S rats on high sodium. PMID- 7875763 TI - Increased calcium stores in platelets from African Americans. AB - Differences in cation transport have been observed between African Americans and whites. These differences may underlie the increased predisposition of African Americans to essential hypertension. To further explore these racial differences, we used platelets as a cellular model for calcium regulation. We measured 45Ca fluxes in platelets from 21 African American and 25 white men. Additionally, using fura 2, we measured cytosolic free calcium levels in resting platelets and platelets treated with ouabain and thrombin. Platelet 45Ca uptake was described by two exchangeable pools: a small, rapidly exchangeable pool and a larger, slowly exchangeable pool. Both pools were larger in platelets from African Americans than from whites (263 versus 185 pmol per 1 x 10(8) platelets for the rapidly exchangeable pool, P < .05; 744 versus 532 pmol per 1 x 10(8) platelets for the slowly exchangeable pool, P < .01). 45Ca washout was described by a rapidly exchangeable pool and a static pool. The former was also higher in platelets from African Americans than from whites (246 versus 202 pmol per 1 x 10(8) platelets, P < .01). The cytosolic free calcium concentrations in resting platelets were lower in African Americans than in whites. After treatment with ouabain and thrombin, the sustained posttransient levels of cytosolic free calcium increased to a greater extent in platelets from African Americans (46.7 nmol/L) than from whites (34.5 nmol/L, P = .033). Platelets from African Americans demonstrate higher intracellular calcium stores than platelets from whites. This racial difference could explain the sensitivity of African Americans to vasoactive agents acting through calcium mobilization from intracellular stores and cytosolic calcium. PMID- 7875765 TI - Effects of different training intensities on the cardiopulmonary baroreflex control of forearm vascular resistance in hypertensive subjects. AB - We recently reported that ambulatory blood pressure decreased during the awake period after training at low intensity but not after training at moderate intensity in subjects with mild to moderate hypertension. The reasons for the failure of moderate-intensity training to reduce blood pressure are not clear. In the present article, we report the effects of different training intensities on cardiopulmonary baroreflex control of forearm vascular resistance, left ventricular function, vascular reactivity, and resistive vessel structure. After moderate-intensity training, the cardiopulmonary baroreflex control of forearm vascular resistance was significantly attenuated, left ventricular performance was enhanced, and vascular reactivity and resistive vessel wall thickness in the calf were reduced compared with values after the control sedentary period. No significant changes in these indexes were found after low-intensity training compared with sedentary values. These results indicate that attenuation of the cardiopulmonary baroreflex control of skeletal muscle vascular resistance after training at moderate intensity may contribute to the lack of antihypertensive effects, as seen from unchanged ambulatory blood pressure levels during the awake period, after training at this intensity. A decreased vascular smooth muscle response to sympathetic nervous stimulation appears to be partly involved in the alteration in the baroreflex control of forearm vascular resistance after moderate-intensity training. Although these findings should be confirmed in a greater number of subjects, the present results point to a key mechanism that might explain why moderate endurance exercise training fails to lower arterial blood pressure in hypertensive subjects. PMID- 7875764 TI - Physiological determinants of hyperreactivity to stress in borderline hypertension. AB - Blood pressure hyperreactivity during stress is characteristic of borderline hypertension in white men. The present study evaluated the hemodynamic basis of this hyperreactivity and assessed its physiological basis in terms of sympathetic nervous system function. Cardiovascular adjustments to an aversive reaction time test were compared with those of the forehead cold pressor test, representing stressors that elicit active behavioral responses in contrast to passive tolerance of aversive stimulation. As anticipated, blood pressure increases were greater in 12 borderline hypertensive men compared with 21 age-matched normotensive men during the active reaction time stressor but not during the passive cold pressor test. The pressor hyperreactivity in borderline hypertensives was associated with excessive rises in plasma epinephrine and norepinephrine, leading to greater increases in cardiac output, despite evidence that the cardiac beta-adrenergic receptors in these subjects were downregulated compared with those of normotensive subjects. During the cold pressor test, borderline hypertension was associated with greater increases in systemic vascular resistance, which, in the presence of normal baroreceptor reflex function, led to an attenuation of cardiac output, thus producing no greater net effect on blood pressure than seen in normotensive subjects. Evidence of vascular hypertrophy in the borderline hypertensive subjects was considered to account for their vascular hyperreactivity to cold pressor stimulation. Collectively, the observations in this study further support the view that the early stages of hypertension in white men are characterized by sympathetic nervous system hyperreactivity, but only in association with tasks that elicit active behavioral coping responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875766 TI - Decreased glomerular basement membrane heparan sulfate proteoglycan in essential hypertension. AB - Heparan sulfate proteoglycans are major components of the glomerular basement membrane and play a key role in the molecular organization and function of the basement membrane. Moreover, their presence is essential for maintenance of the selective permeability of the glomerular basement membrane. Recently, we isolated and characterized a novel small basement membrane-associated heparan sulfate proteoglycan from human aorta and kidney. Partial amino acid sequence data clearly show that this heparan sulfate proteoglycan is distinct from the large basement membrane-associated heparan sulfate proteoglycan (perlecan). Using specific monoclonal antibodies, we have shown that the novel heparan sulfate proteoglycan is located predominantly in the glomerular basement membrane and, to a lesser extent, in the basement membrane of tubuli. Turnover or, in the course of kidney diseases, degradation of heparan sulfate proteoglycan from glomerular basement membranes may lead to urinary excretion of heparan sulfate proteoglycan, which can be measured by a sensitive enzyme immunoassay. The aim of the present study was to analyze whether changes in the structure and function of glomerular basement membranes can be directly detected by measurement of the excretion of a component of this basement membrane, eg, heparan sulfate proteoglycan into urine. The excretion of this small heparan sulfate proteoglycan was compared after physical exercise in normotensive and hypertensive subjects. Normotensive subjects and treated, essential hypertensive patients underwent a standardized workload on a bicycle ergometer. Biochemical characterization of the urinary proteins and heparan sulfate proteoglycan was performed before and 15 and 45 minutes after exercises.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875767 TI - Role of nitric oxide on papillary blood flow and pressure natriuresis. AB - This study examined whether nitric oxide synthesis blockade or potentiation (with N omega-nitro-L-arginine methyl ester [L-NAME] or N-acetylcysteine, respectively) can shift the relations between sodium excretion, papillary blood flow, and renal perfusion pressure. Papillary blood flow was measured by laser Doppler flowmetry. A low dose of L-NAME (3.7 nmol/kg per minute) reduced papillary blood flow only at high arterial pressure (140 mm Hg), but it had no effect on pressure natriuresis. Infusion of 37 nmol/kg per minute L-NAME reduced cortical blood flow by 9% at all perfusion pressures studied, lowered papillary blood flow by 8% and 19% at 120 and 140 mm Hg, respectively, and blunted the pressure-natriuresis response. The administration of 185 nmol/kg per minute L-NAME reduced cortical blood flow by 30% and decreased papillary blood flow by 25% in the range of 100 to 140 mm Hg of arterial pressure. Blockade of nitric oxide synthesis with L-NAME at all doses studied reduced papillary blood flow only at high renal perfusion pressures, but papillary blood flow remained essentially unchanged at low perfusion pressures, thus restoring papillary blood flow autoregulation. N-Acetyl cysteine (1.8 mmol/kg) increased papillary blood flow by 9% and shifted the relations between papillary blood flow, sodium excretion, and renal perfusion pressure toward lower pressures. This effect of N-acetylcysteine on papillary blood flow was blocked by subsequent L-NAME administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875768 TI - Effects of interleukin-1 beta and nitric oxide on cardiac myocytes. AB - Using cultured neonatal ventricular myocytes, we investigated whether nitric oxide (NO) directly influences myocyte growth. Treatment of myocytes with phenylephrine stimulated growth, as indicated by increases in atrial natriuretic factor, brain natriuretic peptide (BNP) mRNA and BNP secretion, activator protein 1 activity (activation of early-response genes), and total cellular protein content. NO was stimulated by treatment of myocytes with interleukin-1 beta (IL-1 beta) or was generated by the NO donor nitroglycerin, and its effects on total protein content and BNP secretion were measured. Treatment of cardiocytes with 3.4 nmol/L IL-1 beta for 24 hours stimulated NO (nitrite) production by threefold, which resulted from an increase in the inducible isoform of NO synthase mRNA. Dexamethasone inhibited IL-1 beta induction of nitrite production, whereas the protein kinase C inhibitor staurosporine had no effect. IL-1 beta had no effect on either basal or phenylephrine-stimulated protein content but inhibited phenylephrine-stimulated BNP secretion. Nitroglycerin (10(-7) to 10(-3) mol/L) dose-dependently increased NO production; however, only the highest dose (10(-3) mol/L) reduced basal and phenylephrine-stimulated total protein content and BNP secretion. cGMP, a second messenger of NO, had no effect on either basal or phenylephrine-stimulated BNP secretion or total protein content. In conclusion, our data indicate that BNP mRNA is stimulated by phenylephrine as shown previously for atrial natriuretic factor. Although both BNP and total protein content are increased by phenylephrine, these effects are not inhibited by NO. However, IL-1 beta inhibits phenylephrine-stimulated BNP secretion but not total protein content, suggesting that regulation of BNP secretion can be dissociated from total protein synthesis during myocyte growth. PMID- 7875769 TI - Cardiovascular changes by long-term inhibition of the renin-angiotensin system in aging. AB - We studied four groups of 20 female mice to evaluate the long-term effect of an angiotensin-converting enzyme on myocardium and vessels during the natural process of aging. Three groups received enalapril in water from weaning to 24 months of age (group A, 20 mg/L; group B, 10 mg/L; group C, 5 mg/L); group D served as a control. Animals surviving after 24 months were killed, and morphometric studies were performed. Total corporal weight was higher in animals receiving enalapril. Cardiac weight relative to total body weight was lower in the treated groups than in the control group. Cardiac morphometric studies showed lower myocardiosclerosis in animals receiving angiotensin-converting enzyme inhibitor (groups A through D, respectively, 0.9 +/- 0.6%, 1.1 +/- 0.2%, 1.03 +/- 0.1%, and 9.5 +/- 4.3%; P < .01, groups A, B, and C versus D). The number of mitochondria per myocardiocyte was higher in the groups receiving enalapril (A through D, respectively, 85 +/- 7, 85 +/- 6, 83 +/- 8, and 58 +/- 8; P < .01, groups A, B, and C versus D). At the vascular level, vessel diameters were not significantly different between the groups receiving angiotensin-converting enzyme inhibitor and the control group, whereas differences were seen in arterial tunica media thickness (wall-lumen ratio) (groups A through D, respectively, aorta: 0.13 +/- 0.02, 0.11 +/- 0.02, 0.12 +/- 0.01, 2.81 +/- 0.35; intrapulmonary: 0.9 +/- 0.43, 0.6 +/- 0.41, 0.8 +/- 0.46, 1.9 +/- 0.51; intracerebral: 2.18 +/- 0.46, 2.29 +/- 0.45, 2.46 +/- 0.43, 3.30 +/- 0.41; intrarenal: 2.28 +/- 0.46, 2.73 +/- 0.48, 2.70 +/- 0.51, 3.23 +/- 0.41; intracariaciac: 2.27 +/- 0.44, 2.59 +/- 0.41, 2.80 +/- 0.43, 3.68 +/- 0.47; P < .001, groups A, B, and C versus D).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875770 TI - Locally generated angiotensin II in the adrenal gland regulates basal, corticotropin-, and potassium-stimulated aldosterone secretion. AB - The zona glomerulosa cells of the adrenal gland have an intrinsic renin angiotensin system that appears to modulate the aldosterone response to potassium and corticotropin. The actions of circulating angiotensin II (Ang II) are mediated by the activation of the Ang II type 1 (AT1) receptor on the adrenal cortex. In this study we examined the effects of the AT1 receptor antagonist DuP 753 and other antagonists on aldosterone secretion in cultured bovine zona glomerulosa cells. Zona glomerulosa cells were cultured in PFMR-4 medium containing 10% fetal calf serum for 72 hours, and the medium was replaced with serum-free medium for the next 24-hour experimental period. DuP 753 (10 mumol/L) inhibited basal aldosterone secretion (from 88.6 +/- 7.1 to 54.8 +/- 9.6 pg/10(6) cells per hour; 38% inhibition). EXP 3174, an active metabolite of DuP 753, also inhibited aldosterone dose dependently (from 88.6 +/- 7.1 to 55.9 +/- 8.4 at 1 mumol/L and 88.6 +/- 7.1 to 21.7 +/- 3.3 at 100 mumol/L; 37% and 75% inhibition, respectively). Another and more potent AT1 receptor antagonist, L158,809, showed significant inhibition at 100 nmol/L, and at 10 mumol/L it inhibited basal aldosterone secretion (from 144.7 +/- 18.2 to 83.4 +/- 17.1 pg/10(6) cells per hour; 42% inhibition). DuP 753 inhibited Ang II (100 nmol/L)-stimulated aldosterone production in a dose-dependent fashion, with a 30% reduction at 100 nmol/L and complete inhibition at 100 mumol/L. DuP 753 also inhibited potassium (12 nmol/L) and corticotropin (1 nmol/L) stimulation of aldosterone in a dose dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875771 TI - Pressure enhances endothelin-1 release from cultured human endothelial cells. AB - The effect of pure pressure without shear stress or stretch on the release of endothelin-1 was investigated. Elevation of pressure significantly enhanced endothelin-1 release from cultured human umbilical vein endothelial cells. A calcium channel blocker, nifedipine, and a putative stretch-activated channel blocker, gadolinium, did not affect the pressure-induced endothelin-1 increase. On the other hand, a phospholipase C inhibitor, 2-nitro-4-carboxyphenyl-N,N diphenylcarbamate, and protein kinase C inhibitors, 1-5-(isoquinolinylsulfonyl)-2 methylpiperazine and chelerythrine, significantly inhibited the pressure-induced endothelin-1 increase. Moreover, pure pressure reduced basal nitric oxide release, while pretreatment with a nitric oxide synthase inhibitor, NG-monomethyl L-arginine, had no effect on the pressure-induced endothelin-1 increase. In conclusion, our results show for the first time that pressure enhances endothelin 1 release partially through activation of phospholipase C and protein kinase. PMID- 7875772 TI - Early blockade of bradykinin B2-receptors alters the adult cardiovascular phenotype in rats. AB - We evaluated whether long-term inhibition of bradykinin B2-receptors by the long acting antagonist Hoe 140 (D-Arg,[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin) affects the blood pressure of normotensive rats. Neither Hoe 140 (at 75 nmol/d for 8 weeks) nor its vehicle altered systolic pressure of adult rats on a normal or high sodium intake. In further experiments, pairs of Hoe 140-treated rats were mated and their offspring maintained on Hoe 140 and a normal sodium diet. Controls were given vehicle instead of Hoe 140. At 9 weeks of age, rats given Hoe 140 during prenatal and postnatal phases of life showed greater systolic pressures, heart rates, and body weights than controls (122 +/- 1 versus 113 +/- 1 mm Hg, 444 +/- 6 versus 395 +/- 8 beats per minute, 258 +/- 7 versus 213 +/- 3 g, respectively, P < .01), whereas urinary creatinine excretion was reduced (1.13 +/- 0.05 versus 1.36 +/- 0.04 mumol/100 g body wt in controls, P < .05). The difference in blood pressure (confirmed by direct intra-arterial measurement) persisted after 20 days of dietary sodium loading, whereas it was nullified by sodium restriction. In additional experiments, the offspring of untreated rats received Hoe 140 or vehicle from 2 days to 11 weeks of age. At this stage, systolic pressure and body weight were significantly greater in Hoe 140-treated rats compared with controls, and heart rate was similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875774 TI - Ambulatory blood pressure measurement and insulin resistance. PMID- 7875773 TI - Poisons and regulators of the sodium pump. PMID- 7875775 TI - Diagnosis and management of perinatal asphyxia: current concepts. PMID- 7875776 TI - Delivery room management of infants born through thin meconium stained liquor. AB - A total of 3472 deliveries were studied over a year to evaluate (i) the importance of thin meconium stained liquor (MSL) in the causation of meconium aspiration syndrome (MAS), and (ii) the efficacy of intrapartum plus endotracheal suction at birth in the prevention of MAS due to thin meconium. Two hundred and ninety four (8.5%) of deliveries had meconium stained liquor of which thin MSL was present in 101. MAS occurred in 98 babies. Thin MSL was responsible for 19.4% of cases of MAS. Inspite of intrapartum suction, a high proportion (55-78%) of infants had meconium in the trachea, though thin meconium was found in the trachea significantly less often than thick meconium. Combined intrapartum and endotracheal suction reduced the incidence of MAS due to thin meconium from 26% to 16%. MAS due to thin meconium occurred in asphyxiated as well as vigorous babies inspite of combined suction. Thin meconium accounts for a significant proportion of deliveries with MSL and causes a considerable number of cases of MAS. To prevent meconium aspiration syndrome caused by thin meconium, all neonates born through thin MSL, whether they are asphyxiated or not should undergo intrapartum suction followed by immediate endotracheal suction at birth. PMID- 7875777 TI - Refractive errors in preterm babies. AB - Fifty preterm neonates were followed up at the age of 6 months and 1 year. In addition to developmental assessment, a complete ophthalmological examination was done on both visits. The largest (62%) gestational age group was of 34-36 weeks. At 6 months, none of the infants had normal vision. At 1 year of age, 64% of the babies had normal vision while incidence of myopia and hypermetropia was 16% and 20%, respectively. There was an inverse relationship noted between gestation and incidence of refractive errors. It was also noted that with decreasing weight, the incidence of myopia increased. Myopia was seen exclusively among infants of birth weight of 2000 g or less. Birth weight had a significant positive correlation with astigmatism. No correlation of asphyxia with refractive errors was observed. It is recommended that all preterm babies should have an ophthalmological examination at one year of age with follow up later on. PMID- 7875778 TI - Congenital malformations at birth. AB - Three thousand nine hundred and thirty-two consecutive newborns were examined at birth for the presence of congenital malformations. The overall incidence of malformations was 1.2%. Congenital malformations accounted for 9.2% of perinatal and 12.8% of neonatal deaths. The central nervous system (39.5%) was most commonly involved followed by musculoskeletal system (14.5%). Involvement of more than one system was observed in 18.8% cases. Though there was higher incidence of malformations in babies born to mothers of more than 35 years the difference was not statistically significant. However, the babies born to mothers of gravidity 4 or more had significantly higher incidence of malformation when compared to mothers of lower gravidity (chi1(2) = 4.67, p < 0.05). The incidence of congenital malformations at birth was higher in stillborn and low birthweight babies. PMID- 7875779 TI - Evaluation of short neck: new neck length percentiles and linear correlations with height and sitting height. AB - Qualitative impressions of neck length are often used as aids to dysmorphology in syndromes like Turner, Noonan, Klippel-Feil and in craniovertebral anomalies, some of which have serious neurological implications. There are no national or international standards for neck length. The present study attempted to create standards and percentile charts for Indian children and compute age-independent correlations of neck length with linear measurements such as standing and sitting height. A total of 2724 children of both sexes between 3 and 15 years, whose heights and weights conformed to ICMR standards were inducted. Neck length was measured by a modified two-point discriminator between two fixed bony points inion and spinous process of C7 with the head held in neutral position. Percentiles (5th-95th) were constructed for both sexes. Growth was rapid from 3 to 6 years. Neck length formed a mean of 12.7 +/- 4.58% of height and 20.1 +/- 6.73% of sitting height. Age independent linear regression equations: Neck length = 10 + (0.035 x height) and Neck length = 9.65 + (0.07 x sitting height) were highly significant (p < 0.001). Neck length relationships of 30 randomly selected normal children clustered around the regression lines and 16 with genetic syndromes fell below the regression lines. PMID- 7875780 TI - Maternal weight, height and risk of poor pregnancy outcome in Ahmedabad, India. AB - This paper explores the relationships between maternal weight, height and poor pregnancy outcome using a data set from a case-control study of low birth weight (LBW) and perinatal mortality in Ahmedabad, India. Maternal height and weights were compared between mothers of 611 perinatal deaths, 644 preterm-LBW, and 1465 normal birth weight controls as well as 617 small-for-gestational age (SGA) and 1851 appropriate-for-gestational-age (AGA) births. Weight and height were much lower in this population compared to western standards. Low weight and height were associated with increased risk of perinatal death, prematurity and SGA. After adjusting for confounders, maternal weight remained significantly associated with poor pregnancy outcomes, whereas height was only weakly associated. Attributable risk estimates show that low weight is a much more important contributor to poor outcome than low height. Improvement in maternal nutritional status could lead to substantial improvement in birth outcome in this population. PMID- 7875781 TI - Outcome in relation to Apgar score in term neonates. AB - Sixty four asphyxiated term babies (Apgar score of 6 or less at 5 minutes) and 90 non-asphyxiated term babies (controls) were studied. Of these, 40 cases and 48 controls could be followed up. Mortality and neurodevelopmental outcome were studied in both the cases and controls. Mortality and poor neurodevelopmental outcome correlated inversely with the Apgar scores at 5 and 10 minutes. The outcome of babies with low 5 minute Apgar scores was significantly better than those with the same scores at 10 minutes. Symptomatic neonates when compared to asymptomatic neonates with same Apgar score showed significantly poorer outcome. Babies with Apgar scores of 6 at 5 or 10 minutes behaved like the controls both in terms of mortality and neurodevelopmental outcome. PMID- 7875782 TI - Determinants of low birth weight: a community based prospective cohort study. AB - The study aimed at identifying and quantifying determinants of low birth weight (LBW) by following a community based prospective cohort of pregnant women in 45 villages in Pune district. In the 1922 live births born to mothers without a chronic illness, in whom birth weight was available within 24 hours, the cumulative incidence of LBW (< 2500 g) was 29%. The unadjusted relative risks for LBW were significantly higher for lower socio-economic status (RR = 1.71), maternal age less than 20 years (RR = 1.27), primiparity (RR = 1.32), last pregnancy interval less than 6 months (RR = 1.48), non-pregnant weight less than 40 kg (RR = 1.3), height below 145 cm (RR = 1.51), hemoglobin less than 9 g/dl (RR = 1.53) and third trimester bleeding (RR = 1.87). Multivariate logistic regression analysis showed that the adjusted odds ratio for LBW decreased with increasing gestational duration, non-pregnant weight, parity and rising education level of the mother. Socio-economic status, non-pregnant weight, maternal height, and severe anemia in pregnancy had substantial attributable risk per cent for LBW (41.4%, 22.9%, 29.5% and 34.5%, respectively). The findings suggest that selectively targetted interventions such as improving maternal education and nutrition, specifically anemia, wider availability of contraception to delay the first pregnancy and to increase pregnancy intervals may help in identifying and ensuring adequate care for those women at greatest risk of LBW. PMID- 7875784 TI - Evaluation of thyroid functions in critically ill infants. AB - The degree to which thyroid functions are affected by non-thyroid illness and an assessment of its correlation with mortality was evaluated. Thirty infants (20 M, 10 F) with a mean age of 433 +/- 3.28 months (+/- 1 SD), with severe acute systemic illness and 30 healthy controls, age and sex matched, were studied for total serum T3, T4 and TSH levels at admission and recovery or before death. Serum thyroid hormones were measured using standard techniques. There was no significant change in thyroid indices with age, sex, nutritional status, serum protein and C-reactive protein. Serum T3 levels in infants were significantly lower (0.62 +/- 0.63 ng/ml) than the controls (1.90 +/- 0.62) (p < 0.001), with normal T4 and TSH levels at admission. Both serum T3 and T4 levels increased with recovery. Out of 30 infants studied, 14 died whereas 16 were discharged. It was noticed that T3 and T4 values were significantly reduced at or near death when compared with the admission levels (p < 0.001). Prognosis could not be determined at the time of admission, as thyroid indices at admission of patients who died, when compared to infants who were discharged, showed no significant difference in T3, T4 or TSH levels. The above mentioned changes in thyroid indices probably occur as a temporary adaptive mechanism to limit catabolism in states of stress such as infection. Hence, it is suggested that thyroid function tests be interpreted with caution in patients with non-thyroid illness. PMID- 7875783 TI - Breast-feeding practices in Schedule Caste communities in Haryana state. AB - A study was conducted to assess exclusive breast-feeding, continued breast feeding, bottle-feeding, predominant breast-feeding, timely complementary feeding and other breast-feeding practices in 818 children in the age group of 0-3 years belonging to the Schedule Caste communities of Haryana. The exclusive breast feeding rate was 0.15 and the predominant breast-feeding rate 0.75 in children < 4 months. Timely complementary feeding rate was 0.42. The continued breast feeding rate at 1 year and 2 years was 0.84 and 0.58, respectively. The bottle feeding rate, ever breast-fed rate, timely first-suckling rate and exclusive breast-feeding rate by mother were 0.09, 1.0, 0.0 and 0.15, respectively. The median duration of breast-feeding was 16 months. PMID- 7875785 TI - Snake venom poisoning: experience with 633 cases. AB - Snake venom poisoning is a common medical emergency and the epidemiological features vary from region to region. We conducted a prospective study to review the epidemiology, treatment and outcome of snake venom poisoning in central Karnataka. Six hundred and thirty three cases of snake bite, seen in a teaching hospital, upto the age of 18 years, over a period of 8 years from 1985 to 1992 constituted the material for the study. Detailed history with special reference to the type of snake, circumstances leading to the bite and clinical consequences were studied and final outcome was noted. Males (n = 433) were bitten more often than females (n = 200). Two hundred and fifty six (40.4%) cases were in the age range of 11-15 years. The cases were seen during two periods, i.e., Oct, Nov, Dec (n = 210) and Apr, May, June (n = 199). Most (n = 506) were encountered in the lower limbs. Viper was the most common poisonous snake. Five hundred and seventy (90%) cases were from rural area. Coagulation time was prolonged in 371 (58.6%) cases, hemorrhagic syndrome was noticed in 354 (55.9%) cases, neurological involvement in 79 (12.5%) cases. Polyvalent anti snake venom (ASV) was given to 479 cases. Hypersensitivity to ASV was noted in 8 cases. Blood transfusion was given to 33 cases for the management of excessive bleeding. The death rate among snake victims was 5.2% (33 cases). The morbidity and mortality can be reduced substantially by increasing and maintaining confidence in good medical care and providing health education. PMID- 7875786 TI - Tuberculous disease in a pediatric referral centre: 16 years experience. AB - Children with evidence of tuberculous disease registered at the TB Clinic, Institute of Child Health, Madras during the years 1977 to 1992 were analyzed. Progressive primary complex, is the commonest thoracic form of tuberculosis while tuberculous meningitis is the commonest extra thoracic form. The overall prevalence of various clinical forms of tuberculosis has decreased over the last 16 years. There is an increasing trend in the prevalence of progressive primary complex among the BCG vaccinated group. The prevalence of pleural effusion, bone tuberculosis and abdominal tuberculosis is almost same over the last 16 years and is more in the BCG non vaccinated children. In tuberculous adenitis there is no significant variation between the two groups. The occurrence of tuberculous meningitis is in the ratio of 1:3 among BCG vaccinated and non-BCG vaccinated children. Though the prevalence of miliary tuberculosis is negligible, it is significantly more in BCG non-vaccinated children. There is a tendency for slight decrease in overall mortality due to tuberculosis in the last 10 years but the mortality due to tuberculous meningitis continues to be the same over the past 16 years. PMID- 7875787 TI - Simple predictors to differentiate acute asthma from ARI in children: implications for refining case management in the ARI Control Programme. AB - There is a considerable overlap in the clinical presentation of acute asthma and ARI. According to the current ARI Control Programme recommendations, a child with cough and rapid breathing is overtreated for ARI (pneumonia) with antibiotics and undertreated for asthma with bronchodilators. The present study, therefore, evaluated simple predictors to differentiate these two conditions to refine the recommended case management. In a case control comparison, children between 6 to 60 months age who presented with cough and rapid breathing due to acute asthma (n = 100) and ARI (n = 100) were evaluated. Only 34% of asthmatics had an audible wheeze. Significant independent predictors on multiple logistic regression analysis were number of earlier similar attacks and fever (or temperature). The best predictor for asthma was two or more earlier similar episodes (sensitivity 84%, specificity 84%) followed by temperature < 37.6 degrees C (sensitivity 73% and specificity 84%). Absence of fever, audible wheeze and a family history of asthma had excellent specificities (98-100%) but low sensitivities (20-34%). It is concluded that simple clinical predictors can differentiate acute asthma and ARI. The recommended case management can, therefore, be refined by either: (i) Prescribing bronchodilators and no antibiotics with two or more earlier similar episodes of cough and rapid breathing; or (ii) To further minimize undertreatment for pneumonia, prescribing bronchodilators as above, but denying antibiotics in such cases only if there is audible wheeze or family history of asthma or no fever. PMID- 7875788 TI - Prenatal diagnosis of Roberts syndrome. PMID- 7875789 TI - Congenital pneumonia caused by Klebsiella pneumoniae. PMID- 7875790 TI - Artery to artery twin disruption sequence. PMID- 7875791 TI - Intravenous immunoglobulin therapy for hyperbilirubinemia caused by Rhesus hemolytic disease. PMID- 7875792 TI - Toxic synovitis of the hip an unusual complication of neonatal salmonellosis. PMID- 7875793 TI - Late sepsis in a G-6-PD deficient newborn. PMID- 7875794 TI - Etiology of neonatal jaundice at Shimla. PMID- 7875796 TI - Profile of malignant lesions amongst children in North Bengal. PMID- 7875795 TI - Cord blood cholesterol in term and preterm newborns. PMID- 7875797 TI - Isolation rate of enteroviruses vis-a-vis number of samples and mode of collection. PMID- 7875798 TI - Glycogen storage disease type III. PMID- 7875799 TI - Impact of television on children. PMID- 7875800 TI - Cyclic neutropenia in common variable immunodeficiency. PMID- 7875801 TI - Hypokalemic muscle paralysis. PMID- 7875802 TI - Gastric outlet obstruction due to solitary gastric polyp in a neonate. PMID- 7875803 TI - Post-operative mental development in patients with hydrocephalus and craniosynostosis. PMID- 7875804 TI - Choroid plexus papilloma. PMID- 7875805 TI - Snake envenomation. PMID- 7875806 TI - Learning problems in children who were "high risk" at birth. PMID- 7875807 TI - Development of mother-infant attachment scale. AB - A 15 item mother-infant attachment scale was developed. It is a simple, brief and easy to comprehend even by the illiterate rural woman. The split half reliability was found to be 0.83 and there was high internal consistency. It has high face and construct validity. The babies separated for longer period had shown lesser attachment subsequently, compared to those who had no separation. PMID- 7875808 TI - Catch up growth and its determinants in low birth weight babies: a study using Z scores. AB - Two hundred and forty seven low birthweight (LBW) survivors of our Neonatal Intensive Care Unit and 164 normal birthweight controls were followed up longitudinally from birth to 4 years and their growth trends (weight, height, head circumference) were expressed as mean Z scores in 500 g birthweight categories. Whereas LBW's demonstrated rapid growth in the first 6 months of life, followed by generally parallel trends with some tendency to rise, controls showed distinct growth faltering especially after one year. Only 30.8% of LBWs (and 49% of controls) were within the designated catch up levels for weight by age 4 years. The corresponding number for catch up of height and head circumference in LBW's was 22.8% and 26.5%, respectively. On multiple regression analysis, the most important determinants of catch up (at 4 years) in LBW's were weight at 1 year (beta = 0.51), height at 1 year (beta = 0.31) and mother's weight (beta = 0.04). Thus, Z scores enabled the demonstration of changing growth trends, simultaneous comparisons with local controls and international standards and comparison within indices. Growth charts incorporating Z score should be made available in a simplified manner for use in the community. PMID- 7875809 TI - Salmonella senftenberg: epidemics in India and present status. PMID- 7875810 TI - Optimum age of a child for BCG vaccination. AB - The objectives of this study were to evaluate whether a newborn or a neonate is capable of responding immunologically after BCG vaccination and to find out if this immunity persists for one year. Normal infants aged between 0 days-3 months brought to immunization centre were included in the study. In vitro leukocyte migration inhibition test was performed in these children using Phytohemagglutinin and purified protein derivative (PPD). They were grouped based on their age at vaccination, their LMI values and on the time interval after vaccination. The mean values of % LMI (PPD) in all the age groups were positive and there were no significant differences between the newborns, the neonates and other groups. The values were positive and comparable even after 12 months in all the groups. The percentage of infants with positive or negative values to LMI (PHA) and negative values to LMI (PPD) were also comparable at different time intervals in different age groups. The results suggest that newborns or neonates are as capable of eliciting a positive immune response after BCG vaccination, as older infants and the practise of vaccinating a child at birth could be continued. PMID- 7875811 TI - The intraosseous route is a suitable alternative to intravenous route for fluid resuscitation in severely dehydrated children. AB - It is sometimes difficult to gain a rapid intravenous access in hypovolemic states. The suitability of intraosseous (IO) route for fluid infusion as an effective, safe and reliable alternative to intravenous (IV) route was explored. Sixty children (age range 3 months to 2 years) with severe dehydration were assigned alternately to receive resuscitating fluid through either IO or IV routes. The IO route was successfully secured in all cases within the first 5 minutes of attempt. On the other hand, the IV line could not be secured in 33% (10 out of 30) patients within 5 minutes. The time taken for IV cannulation when it was successful (129 +/- 13 seconds, 95% confidence interval 103-156 seconds) was significantly longer than the time taken for IO cannulation (67 +/- 7 seconds, 95% confidence interval 55-80 seconds). Fluid infusion through either routes was equally effective in stabilizing vital signs and normalizing laboratory abnormalities. No significant complication of IO route was noted on short term follow-up. We conclude that IO route is a safe, effective alternative for emergency fluid administration in severe dehydration when intravenous line cannot be secured rapidly. PMID- 7875812 TI - Diagnostic value of gene probes and its correlation with clinical profile of leprosy in children. AB - Clinico-bacteriological profile of 73 leprosy patients below 16 years of age was studied. Majority of the patients were males and fell in 11-16 years age group (p < 0.05). Skin lesions were present in all cases on both exposed as well as unexposed areas and their number increased with advancing age. Cutaneous sensations were affected in most of the patients while nerve thickening was observed in 41. As age increased, the disease moved from the tuberculoid end of spectrum towards the lepromatous end (p < 0.05) and the positivity of the skin smears increased (p < 0.05). Majority of the paucibacillary cases were lepromin positive while most multibacillary cases were lepromin negative (p < 0.01). Two M. leprae specific gene probes were applied in 42 cases to assess their diagnostic value. Eighty one per cent cases were picked up by the probes indicating presence of active bacilli. These included all lepromin positive cases, all smear positive cases, and most of smear negative cases (p < 0.05). Seven children with inconclusive histology were also positive. Drug treatment and inadequate size of biopsy sample could explain the negative probe results in 19% cases. This study highlights the immense potential of gene probes in diagnosing leprosy in children. PMID- 7875813 TI - Waning of post vaccinial allergy after neonatal BCG vaccination. AB - Tuberculin sensitivity or post vaccinial allergy (PVA) is widely used as an indicator of successful BCG vaccination. The protection conferred by BCG vaccination, the duration of post-vaccinial allergy and the relationship between the two remain a subject of controversy. The present study was conducted with the aim of finding the duration of PVA and evaluate the need for revaccination. One thousand newborns were given BCG under controlled conditions and followed up for PVA by serial PPD (5TU) injection at 3, 6, 12, 24, 30 and 36 months. An induration of 5 mm or less was recorded as negative and no subsequent testing was done. At 3 month, all the infants were given PPD and 95.3% showed a positive response. The positivity rate declined significantly (p < 0.01) to 19% by 3 years of age. A statistically significant (p < 0.01) fall in the mean PPD induration size was also noted. At 3 months, the mean induration size was 10.68 mm but by 3 years it had decreased to 3.86 mm. The distribution of PPD size also showed that with the increase in age, there was a shift towards the smaller size. At 3 years of age, none of the children had an induration of more than 10 mm. The booster effect due to repeated PPD testing was seen in a small percentage and only at 6 and 12 months test. Subsequently no increase in PPD induration was noted. Sex of the child did not influence the PPD induration size significantly (p > 0.05). At 3, 6 and 12 months of age, significant correlation between BCG lesion and PVA was noted, the co-efficient of correlation being 6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875814 TI - Practices of chemists regarding diarrhea management. PMID- 7875815 TI - Prevalence of 'at risk' factors in under five children. PMID- 7875816 TI - Reactive monoarthritis. PMID- 7875817 TI - Massive osteolysis--Gorham's syndrome. PMID- 7875818 TI - Profile of childhood disability. PMID- 7875819 TI - Langerhans cell histiocytosis with characteristic skin involvement. PMID- 7875820 TI - Chloroquine resistance in malaria. PMID- 7875821 TI - Solitary rectal ulcer in a child treated with local sulfasalazine. PMID- 7875822 TI - Accidental poisoning. PMID- 7875823 TI - Factors influencing initiation of breastfeeding in an urban set up. PMID- 7875824 TI - Jaundice--a rare presentation of tuberculosis. PMID- 7875825 TI - Supernumerary teeth presenting as nasal teeth. PMID- 7875826 TI - Spoon feeds--an alternative to bottle feeding. PMID- 7875827 TI - Tuberculous meningitis in early infancy. PMID- 7875828 TI - Retroperitoneal lymphangioma presenting as an inguinal hernia. PMID- 7875829 TI - Familial glioma. PMID- 7875830 TI - Familial adenomatous polyposis coli. PMID- 7875832 TI - Pediatric laparoscopy current state and future. PMID- 7875831 TI - BCG revisited. PMID- 7875833 TI - Clostridium difficile in antibiotic associated pediatric diarrhea. AB - A case control study was carried out at the medical wards of Dr. B.C. Roy Memorial Hospital for Children, Calcutta, between January and September 1989. One hundred eleven hospitalized children up to the age of 5 years, receiving antibiotics for different medical problems, developed antibiotic associated diarrhea. Isolation of Clostridium difficile as sole pathogen was very low (3.6%) from these patients. Fecal samples of 111 case matched control children were also screened for C.difficile. Only 2.7% fecal samples of control children were positive for C.difficile. All the strains of C.difficile isolated from antibiotic associated diarrhea cases showed neutralisable cytotoxin in in vitro test. In contrast none of the strains isolated from control children showed cytotoxicity. This study suggests that C.difficile is not an important pathogen related to antibiotic associated diarrhea in children at this hospital. PMID- 7875834 TI - Iron nutritional status of adolescent girls from rural area and urban slum. AB - Iron nutritional status of adolescent girls belonging to an urban slum and rural areas was assessed by measuring serum ferritin levels. Overall anemia was observed in 25% of the girls irrespective of their urban rural residence. A higher percentage of rural girls (37.5%) especially below the age of 12 years showed evidence of anemia. Thereafter, the prevalence was similar in both urban and rural girls who had not attained menarche. With increasing age, urban girls who had attained menarche showed an increase in the prevalence of anemia. The prevalence of iron deficiency (serum ferritin < 12 micrograms/dl) showed a progressive increase from 60% at < 12 to 28% at > 14 yrs especially in the girls not attained menarche in the girls not attained menarche in the rural area. Overall iron deficiency was of much higher order in the rural girls irrespective of the menarcheal status. Distribution of iron/folate tablets to cover girl population may go a long way to correct the anemia and iron deficiency in the vulnerable groups. PMID- 7875835 TI - Immunogenicity and feasibility of purified chick embryo cell vaccine. AB - Two hundred seventy-one children reported at the WHO Collaborative Centre for Rabies Epidemiology for South-East Asia at National Institute of Communicable Diseases, Delhi, for advice and antirabies antibody assessment after post exposure prophylaxis with purified chick embryo cell (PCEC) antirabies vaccine from January 1986 to October 1992. Vaccine was very well tolerated by these children and only 7% complained about mild to moderate side reactions like pain, induration, fever or rash. On an average, every year 50-55 children had reported at this Centre after post-exposure vaccination with PCEC vaccine excepting years 1986 and 1987. One hundred and forty-four children underwent complete course of post-exposure prophylaxis, i.e., 5 or 6 doses on day 0, 3, 7, 14, 30 and 90 (optional) of PCEC vaccine were administered, forty-three (43) children received 4 doses on day 0, 7, 14 and 30 (day 3 dose was omitted) and eighty-four (84) children received 2 to 3 doses as the biting animals were alive for 10 days in these cases. Two hundred and twenty-nine children (84.5%) were bitten by dogs and in 10%, the dog was proven rabid by laboratory examination of dog brain. One hundred and forty-nine (55%) had Class III bite. Serological response, i.e., antirabies antibody titre in all these children were satisfactory (> 0.5 IU/ml) with mean titre of 1.98 IU/ml irrespective of doses of PCEC vaccine administered. No vaccine failure was observed in this study. PMID- 7875836 TI - Immunization coverage of infants--rural-urban difference in Kerala. AB - A study on the Immunization Coverage relating to the six vaccine preventable diseases was carried out in an urban, semi urban and rural area in Kerala and the results from the three areas were compared and discussed. The percentage of fully immunized children was similar in all the three areas and it was quite high. Coverage of measles vaccine was high in the Health Unit, Pangappara where health education activities were carried out by the interns. The awareness about vaccine preventable diseases was more in the urban and semiurban areas. The drop out rate for DPT and OPV was also less in urban and semiurban than in the rural areas. More than 50% of the households in urban, semiurban and rural areas were unaware of the diseases prevented by DPT vaccine. Intense Health Education Campaign can definitely improve the immunization coverage further in a state which has already attained total literacy. PMID- 7875837 TI - High and low dose clonidine tests for the diagnosis of growth hormone deficiency. AB - The growth hormone (GH) response to three provocative stimuli was assessed in 15 short normal children (ISS) and 5 children with GH deficiency (GHD). The pharmacologic agents used were insulin 0.1 unit/kg IV (IHT), oral clonidine 0.15 mg/m2 (HDCT) and 25 micrograms irrespective of age and weight (LDCT). Blood glucose and GH were measured at 0, 30, 60, 75, 90 and 120 minutes; and BP and serum cortisol levels were measured during clonidine tests. A steep rise in GH levels were found between 60 and 90 minutes during HDCT and LDCT. The peak GH levels were 29.5 +/- 5.7 ng/ml in HDCT compared to 17.9 +/- 5.7 ng/ml during IHT and 6.7 +/- 2.9 ng/ml during LDCT (p < 0.01). The peak GH levels above 7 ng/ml were seen in 60% children with ISS during LDCT. No significant adverse effects were noticed during HDCT and LDCT except transient drowsiness. The peak GH levels were not related to the fall in BP or cortisol levels. LDCT appears to be a reasonably effective stimulator of GH release. It can be used for screening children with reduced growth velocity as an outpatient procedure. Those with an abnormal response will need a more definite testing such as HDCT. PMID- 7875838 TI - Psychosocial development of urban children (below 2 years) using culture appropriate indicators of development. AB - Six hundred essentially normal children 15 days-2 years were randomly assessed for their nutritional and developmental status. Measurement of the mid-upper-arm circumference using the Jellife's technique was employed for a quick nutritional survey. For developmental assessment, the WHO suggested culture appropriate psychosocial Basic Test Battery was used. Shakir's classification of the results did not reveal any malnutrition. Analysis of the data revealed 'at par' performances in Gross Motor, Hearing and Self Help skills and delays in Vision and Fine Motor, Language and Concept Skills. Social skills were particularly advanced. PMID- 7875839 TI - Anterior fontanel size. AB - Anterior fontanel size was determined in a cross-sectional study of 445 infants ranging in age from newborn period to 2 years. The mean anterior fontanel size in neonates was 3.37 +/- 0.61 cm which decreased to 0.37 +/- 0.06 cm in 24 months age group. The age of closure of anterior fontanel was 12, 18 and 24 months in 40%, 70.4% and 91.3%, respectively. PMID- 7875840 TI - Treatment of nephrotic syndrome. AB - There are well defined therapeutic protocols for childhood nephrotic syndrome. Appropriate therapy helps in minimizing side effects besides decreasing referrals to tertiary care centres. We have analysed the appropriateness of therapy of primary care physicians in 111 children with nephrotic syndrome referred to our Institute from January 1989 to December 1991. Prednisone was administered in adequate doses in 51 (52.6%), and for adequate duration in 41 children (42.2%). Adjunctive cyclophosphamide therapy was administered in the recommended doses and duration in 33% of the cases. On evaluation of the therapy it was observed that inappropriate treatment had been administered by 39.4% of the pediatricians, 59% of internists and 80% of general practitioners. This study highlights the lacunae in the current state of knowledge amongst the primary physicians and highlights the need for creating greater awareness regarding the therapy of children with nephrotic syndrome. PMID- 7875841 TI - Predictors of serious bacterial infection in infants up to 8 weeks of age. AB - During a period of 2 years we prospectively studied 116 infants up to 8 weeks of age with suspected sepsis. Each infant was assessed clinically before laboratory evaluation for sepsis. Depending upon impression of sepsis, temperature abnormality, micro ESR (mESR), WBC counts and toxic granulations infants were assigned to either high (n = 74) or low (n = 31) risk group for serious bacterial infection (SBI). All infants were kept under observation till the final decision for hospitalization was made. Eighty six per cent of cases in high risk group and 26% of cases in low risk group were hospitalized and treated with antibiotics. SBI was present in 55% of the high risk group infants compared to one (3%) in the low risk group. Culture for bacterial infections were positive in 22 (19%) cases; bacteremia was found in 15 (13%) infants. None of the variables individually predicted the presence of bacteremia or SBI satisfactorily. Presence of two or more criteria out of the three criteria namely impression of sepsis, raised mESR and toxic granulation could identify 93% of infants with bacteremia and 95% of those with SBI and excluded 89% of cases without SBI. PMID- 7875843 TI - Clinical profile of multi drug resistant typhoid fever in Jaipur City. PMID- 7875842 TI - Cavitating pulmonary tuberculosis below age of 2 years. AB - A prospective study was conducted on 75 consecutive cases of primary cavitary pulmonary tuberculosis in hospitalized children below 2 years to determine the spectrum of the disease. Diagnosis was based on clinical, radiological, tuberculin test and histopathological findings and not on isolation of tubercle bacilli. Peak age was 7-12 months. Ten mothers suffered from pulmonary fibrocavitary disease and 73% of cases were severely malnourished. Presenting symptoms were fever and cough, at times dyspnea and often followed measles. Unlike adults, hemoptysis was seldom encountered. Cavitary lesions were characterized by protean radiological manifestations and varied in size and appearance. They were more often multiple than solitary, bilateral or distributed in one or more lobes, usually in the right lung. Location within consolidation and other associated pulmonary pathology was frequent with miliary nodules in 45.3%. Widespread hematogenous infection was common with tuberculous meningitis in 28%. The accepted diagnostic features of tuberculosis, viz., hilar and mediastinal lymhadenopathy and positive tuberculin test were often absent. Mortality was 34.7% and in inverse proportion to age. The observations stress the difficulties in diagnosis [corrected]. PMID- 7875844 TI - Cefotaxime in multi drug resistant typhoid fever. PMID- 7875845 TI - Clinical profile and therapy in enteric fever. PMID- 7875846 TI - Comparison of ciprofloxacin versus cephelexin and gentamicin in the treatment of multi-drug resistant typhoid fever. PMID- 7875847 TI - Diazo test in typhoid fever. PMID- 7875848 TI - HIV related immune thrombocytopenia. PMID- 7875849 TI - Fatal fulminant hepatic failure due to sodium valproate in an adolescent. PMID- 7875850 TI - Spread of scabies and pediculus humanus among the children at Sivas orphanage. PMID- 7875851 TI - Giant choledochal cyst. PMID- 7875852 TI - Management of urinary tract calculi by extracorporeal shock wave lithotripsy. AB - From July 1989 to April 1993, Extracorporeal Shockwave Lithotripsy (ESWL) was performed on 642 patients, of which 21 were from the pediatric age group. All treatments were done on a second generation lithotriptor-Siemens Lithostar, which does not require any modification for positioning of children. Fragmentation was achieved in all the patients (100%). A complete stone free rate was achieved in 17/21 patients (80.9%). Three (14.3%) patients had insignificant residual fragments whereas 1 (4.8%) had a residual fragment approximately 4 mm in size. 5640 shocks were required on an average. We have used low energy shockwaves with good results. General anesthesia was required for lithotripsy in only one child. The average fluoro exposure time was 1.6 minutes. We conclude that ESWL is a safe and effective method for treating urinary tract calculi in children. PMID- 7875853 TI - Balloon valvotomy for severe aortic stenosis in an infant. PMID- 7875854 TI - Enterogenous intramedullary cyst. PMID- 7875855 TI - Use of ciprofloxacin and its resistance in typhoid fever. PMID- 7875856 TI - Venous thrombosis in enteric fever. PMID- 7875857 TI - Rational drug therapy an alternative approach. PMID- 7875858 TI - Glycogen storage disease. PMID- 7875859 TI - Communication skills in clinical practice fad or necessity? AB - Communication skills of 40 final year medical students were assessed using Objective Structured Clinical Examination. The scores obtained were significantly less than those obtained in clinical skills. There was no significant correlation between the two sets of scores. It is suggested that emphasis should be placed on developing and evaluating communication skills during undergraduate medical curriculum. PMID- 7875860 TI - Utility of growth monitoring: its relevance in the promotion of child health. PMID- 7875861 TI - Present day concepts on promotion of breastfeeding in India. PMID- 7875862 TI - Physical growth in Indian affluent children (birth-6 years). AB - Growth characteristics, viz, height, weight and circumferences of head, chest and mid-arm were measured on urban affluent children from seven centres (Bangalore, Calcutta, Delhi, Kota, Ludhiana and Varanasi--Nutrition Foundation of India study). On each age and sex point there were 200 observations except at 18 and 72 months. The percentiles on pooled data were calculated by smoothed cubic spline least square method. This pooled data showed values lower than European and NCHS (American) standards. Centrewise comparison showed that Ludhiana children approached the latter. The differences in growth seem to be possibly due to lower velocity in Indian children of present study in the first 18 months as compared to American children. PMID- 7875863 TI - Clinical predictors of hospitalization in an acute attack of bronchial asthma. AB - The present study was undertaken to identify the clinical predictors of hospitalization in an acute attack of bronchial asthma in subjects aged 2-12 years. Seventy five children with an acute attack of bronchial asthma were evaluated. A detailed clinical history and examination was recorded and baseline investigations sent before starting therapy. All subjects were treated with injection adrenaline (two doses) and those who did not respond were hospitalized. Twenty subjects who were hospitalized were compared with 32 cases who were discharged and did not have a relapse on follow up. After multivariate analysis, the factors independently predictive of hospitalization were, pulsus paradoxus (> 10 mm Hg; OR = 1.02), younger age (below 5 years, OR = 0.98) and severe accessory muscle use (OR = 89.6). Presence of any 2 of these 3 clinical predictors has a high sensitivity (90%) and specificity (96%). The investigative variables significant after multivariate analysis were low pH (OR = 0.00) and polymorphonuclear leucocytosis (> 70%) on peripheral smear (OR = 1.12). The sensitivity of this model was similar (90%) but specificity was lower (90.6%). The addition of investigative variables to clinical model did not improve the predictability. It is concluded that it is possible to identify at presentation, children with acute bronchial asthma who require hospitalization and clinical variables are sufficient for this purpose. PMID- 7875864 TI - Socio-economic burden of childhood asthma. AB - The socio-economic burden of childhood asthma has not been assessed in India. We interviewed parents of asthmatic 85 children in the age group of 6-17 years who were suffering from asthma. Socio-economic burden of asthma was assessed by using Pai and Kapur's interview schedule and the results were analyzed by using Chi square, Student's 't' test and Pearson's product movement correlation coefficient. Severe burden was experienced by the family in 25.9% cases. Total burden score was significantly associated with severity of asthma (p < 0.001) and socio economic status of the family (p < 0.01). These results indicate that there is need for health professionals and social support organizations to chalk out programmes to provide support at least to families of children with chronic/recurrent illness like bronchial asthma in order to reduce the anxiety and other hardships suffered by the families. PMID- 7875865 TI - Variable expression of clinical features of Martin Bell syndrome in younger patients. AB - The clinical features of 20 patients of Martin Bell syndrome were analyzed in order to derive diagnostic features in younger patients. The characteristic clinical features comprising long face, large ears and macro-orchidism were commoner in children more than 10 years old than in prepubertal children. This study shows that younger the patient, fewer the classical features exhibited. Hyperactivity was the most useful feature for diagnosis of the younger patient with Martin Bell syndrome. PMID- 7875866 TI - Reversal of clinical and dental fluorosis. AB - A large number of Indians are forced to consume fluoride contaminated water. Toxic effects of chronic fluoride ingestion are hitherto considered irreversible. In this study 20 children were selected from an area consuming water containing 4.5 ppm of fluoride (Group A) and a second sample of 20 children from another area consuming water containing 8.5 ppm of fluoride (Group B). All the children were in an age group of 3 to 12 years and weighed 12 to 25 kg. Both samples were graded for clinical, radiological and dental fluorosis. All grades of manifestations were observed. These children were given ascorbic acid (500 mg), calcium (250 mg) and vitamin D3 (800 IU) daily. Follow up revealed reversal of clinical and dental fluorosis after 44 days. Improvement in the Group B sample was slower than Group A. Dosage of ascorbic acid was increased to 750 mg per day, keeping the dosages of other drugs unchanged to Group B children. After 15 days of the revised therapy a marked improvement was noticed in clinical and dental fluorosis in this sample also. PMID- 7875867 TI - Chediak-Higashi syndrome--accelerated phase. PMID- 7875868 TI - Familial testotoxicosis. PMID- 7875869 TI - Filarial chyluria. PMID- 7875870 TI - Knowledge, attitude and practice of maintenance of cold chain in immunization. PMID- 7875871 TI - Klebsiella pneumoniae osteomyelitis in sickle cell anemia. PMID- 7875872 TI - Frequency and significance of potassium disturbances in sick children. PMID- 7875873 TI - Defective opsonophagocyte function in newborns studied by luminol dependent chemiluminescence. PMID- 7875874 TI - Anthropometric data in term newborns. PMID- 7875875 TI - Colloid cyst of the third ventricle. PMID- 7875876 TI - Giant perirenal lipoma masquerading as Wilms' tumor. PMID- 7875877 TI - Methods for assessment of dietary intake. PMID- 7875878 TI - 'M' pattern temperature in resistant typhoid fever. PMID- 7875879 TI - Biochemical basis of inflammation with special reference to acute bacterial meningitis. PMID- 7875880 TI - Adolescent health care: international initiatives. PMID- 7875881 TI - Color Doppler evaluation of uteroplacentofetal circulation in management of high risk pregnancies. AB - The study group consisted of 75 high risk singleton pregnancies in whom color duplex Doppler evaluation of the uteroplacental circulation was determined and correlated with perinatal outcome. Uterine, umbilical and middle cerebral artery flow velocity waveforms (FVW) were analysed and the resistance index (RI), pulsatility index (PI) and the systolic/diastolic (S/D) ratios measured. On the basis of the FVW the uteroplacentofetal blood flow was classified as normal, increased resistance to flow, absent end diastolic flow (AEDF), and reversed end diastolic flow (REDF). Ultrasound biometry was simultaneously performed for all fetuses, while non stress testing was performed as and when indicated. Of the 75 fetuses studied 33 (44%) had abnormal FVWs and only 30.3% of these had an uncomplicated outcome as compared to 81% of those with normal flows. The mortality in cases with abnormal flows was 43% as compared to 7% in those with normal flows. There were 40 growth retarded fetuses in the study group of which 30 (75%) had abnormal umbilical artery FVWs. Of the 18 fetuses with AEDF or REDF, all (n = 7) in whom timely obstetric intervention was not done died in utero, irrespective of fetal weight and gestational age, however 75% of these with weight > 1000 g survived when delivered by cesarean section. PMID- 7875882 TI - Incidence of congenital heart disease among hospital live births in India. AB - Ten thousand nine hundred and sixty four consecutive live births weighing more than 500 g and more than 28 weeks of gestation were subjected to a thorough clinical examination within 24 h of birth. Those suspected of having congenital heart disease (CHD) were followed up every 4-6 weeks for a period of 6 to 18 months (mean 9.75 months). Forty three of 10,964 infants had CHD, i.e., 3.9/1000 live births. Incidence of CHD was higher in pre-terms as compared to full term live births (22.69 vs 2.36/1000 live births). Diagnosis was confirmed by echocardiography including 2D, Doppler and color flow imaging. Twenty eight per cent of the infants with CHD had other associated somatic anomalies, Down's syndrome being the commonest (9.3%). Patent ductus arteriosus (41.9%) and ventricular septal defects (VSD) (34.9%), were the commonest lesions with an incidence of 1.6 and 1.4/1000 live births, respectively. Incidence of PDA was higher probably because of larger number of pre-term deliveries. During follow up of 6-18 months, 34.9% of the infants with CHD died. The diagnosis of CHD was confirmed at autopsy in 20% of the deaths. PMID- 7875883 TI - Intramuscular injection as a provocative factor in paralytic poliomyelitis. PMID- 7875884 TI - An outbreak of poliomyelitis in Andhra Pradesh (South India). AB - An outbreak of poliomyelitis that occurred in the year 1992 in Telangana region of Andhra Pradesh, South India was investigated to understand the reasons for persistence of poliomyelitis in the general population and for the outbreak in Andhra Pradesh in particular. The study comprised of a detailed investigation of epidemiological and clinical features, serology and vaccination status and a case control study to calculate vaccine efficacy by matched pair analysis. The outbreak occurred after a relative quiescence of 3 years. The age group of the patients ranged from 2 months to 5 years, 26.5% being infants and 70.2% being children between 1 and 5 years. The outbreak was mainly caused by Type 1 poliovirus. Vaccine efficacy was found to be 70%. Antibody response was not high in cases. Seventy six per cent of the children with poliomyelitis were unvaccinated. Ignorance of the mothers and family interference were the main causes for not vaccinating the children. The study indicates the need to increase the vaccination coverage and inclusion of children upto 5 years in the programme. Absence of vaccination is the major risk factor for the outbreak. The persistence of poliomyelitis in older children, low antibody response and suboptimal vaccine efficacy point out the problem of achieving control with OPV in tropical countries and suggest the need for alternate strategies. Better health education strategies need to be developed. PMID- 7875885 TI - Measles outbreak in a tribal population of Thane district, Maharashtra. AB - In March 1992, an outbreak of measles, in the tribal population of Vavar village, Mokhada Taluk, Thane district, Maharashtra, was investigated. Two hamlets of Vavar village namely Sagpanipada (epidemic in October, November 1991) and Behedpada (epidemic in January, February 1992) were affected. In both hamlets, measles cases were confined to children below 10 yrs and 96% of the cases occurred in children below 6 yrs. Attack rates were 52.7% and 51.4% and case fatality rates were 31.2% and 15.6% at Sagpanipada and Behedpada, respectively. All the convalescent patients' sera possessed IgM antibodies against measles. A clear drop in IgM and a rise in IgG antibodies against measles was observed in 35 paired samples from convalescent patients. Fifty four per cent of sera from controls, possessed IgM antibodies. Migrating population appeared to have imported measles which flared up in an epidemic among the susceptibles. Priority immunization of the children of remote isolated populations may prevent such epidemics. PMID- 7875886 TI - Evaluation of an innovative school eye health educational mode. AB - An innovative mode of using school children as health educators for transmitting messages on eye health care in the school environment was evaluated. Fifty children were evaluated at baseline and immediately after the educational session. A significant change in cognitive aspects of eye care was demonstrated (p < 0.001). Knowledge on vitamin A related aspects and childhood ocular trauma improved substantially compared to all other aspects of eye care. PMID- 7875887 TI - Co-existence of oblique pinnae and congenital heart disease. AB - The paper reports a syndrome in which oblique placement of one or both the pinnae on face was found to co-exist with congenital anomalies of heart like VSD, PDA and Tetralogy of Fallot, etc. Although clinically discernible in 90% of the subjects, objective evidence of obliquity of pinna was documented by photogrammetry. The values for the ear inclination in subjects categorized clinically as normally placed pinna were 7.9 degrees +/- 3.39 degrees with range 2 degrees-17 degrees. In contrast, subject where the pinna was clinically categorized as oblique had mean AEI 16.5 degrees +/- 5.81 degrees with a range 5 degrees-33 degrees. Eighteen of the 20 subjects with oblique pinna were demonstrated to have some congenital anomaly of heart as indicated by clinical and echocardiographic examination. In contrast, in subjects with normally placed pinna only 3 out of 34 possessed clinical heart defects. Presence of oblique pinna indicates a thorough search for undetected heart defects. PMID- 7875888 TI - Safety and efficacy of a concentrated potassium chloride solution infusion for rapid correction of hypokalemia. AB - Twenty children with hypokalemia (plasma potassium concentration < or = 3.5 mmol/L) with electrocardiographic (ECG) changes were given an infusion of concentrated solution of potassium chloride (200 mmol/L) at a rate of 0.25 mmol per kg per hour till ECG changes reverted to normal, under close monitoring of vital signs and ECG. The regimen effectively corrected the ECG changes in 1 to 6 hours with a mean increase in serum potassium by 0.75 +/- 0.49 mmol/L. No complications occurred. Controlled infusion of a concentrated solution of potassium chloride at a rate of 0.25 mmol/kg/hour is a safe and effective way to achieve rapid correction of hypokalemia with ECG changes, using minimal fluid volumes. PMID- 7875889 TI - Health status of carpet weaving children. AB - A cross-sectional study was undertaken to determine the health status of children engaged in carpet weaving factories of Jaipur City. Two hundred and ninety school going boys of similar socio-economic status served as controls. A higher prevalence of signs of nutritional deficiencies was observed in carpet weaving children. Analysis of the presenting complaints and the illness suffered in the past six months also revealed a significantly higher morbidity in these children. A statistically significant difference was also observed in anthropometric measurements of the two groups. PMID- 7875890 TI - Ketorolac. PMID- 7875891 TI - Isolated vertebral body relapse of acute lymphoblastic leukemia. PMID- 7875892 TI - Relationship between prepucial Epstein pearls with gestational age, birth weight and birth order. PMID- 7875893 TI - Management of supraventricular tachycardia in infancy and childhood. PMID- 7875894 TI - Truncus arteriosus and depressor anguli oris muscle deficiency. PMID- 7875895 TI - Alkaptonuria: early detection. PMID- 7875896 TI - Efficacy of halofantrine in malaria. PMID- 7875897 TI - Aerococcus viridans endocarditis. Case report. PMID- 7875898 TI - Sacral agenesis. PMID- 7875899 TI - Superior sternal cleft. PMID- 7875900 TI - Unusual polydactyly foot. PMID- 7875901 TI - ESR estimation in fasting and post prandial state. PMID- 7875902 TI - Extrapyramidal syndrome following ciprofloxacin treatment. PMID- 7875903 TI - Post-polio residual paralysis in rural areas--place of physical therapy. PMID- 7875904 TI - Enuresis updated. PMID- 7875905 TI - Airway management: a perspective. PMID- 7875906 TI - The laryngeal mask airway--role in managing the difficult airway. PMID- 7875907 TI - Practical aspects of fiberoptic laryngobronchoscopy. PMID- 7875908 TI - Models to facilitate the learning of fiberoptic technique. PMID- 7875909 TI - Performing fiberoptic endotracheal intubation: clinical aspects. PMID- 7875911 TI - Transtracheal oxygenation and ventilation. PMID- 7875910 TI - Fiberoptic-aided endobronchial intubation. PMID- 7875912 TI - Cricothyrotomy. PMID- 7875913 TI - Transition to retirement: gender differences. AB - The present investigation consisted of two studies which attempted: 1) to assess the replicability of the investigation by Wapner and Hornstein [1] and Hornstein and Wapner [2,3] that uncovered four distinct modes of experiencing the transition to retirement, and 2) to advance that work by focusing on gender differences. The preliminary study, based on analyses of twenty-four case studies reported by Wapner and Hornstein suggested it would be profitable to study gender differences in a more systematic manner [1]. Toward this end, the major study involved construction of four appropriate instruments which were administered to ninety-four (48 women, 46 men) recent retirees. The four retirement categories (I. Transition to Old Age; II. New Beginning; III. Continuation; IV. Imposed Disruption) described in those investigations was replicated. Moreover, striking gender differences emerged. Theoretical and practical implications of the study were explored. PMID- 7875914 TI - Attitudes toward mandatory retirement: an international comparison. AB - Over recent decades, whether legislation supporting mandatory retirement should exist has been debated frequently. The issue has been exacerbated by the growing number of elderly people within western societies. Using nationally representative data from the United States of America, West Germany, Great Britain, and Australia, this article provides an international comparison of individual's attitudes toward mandatory retirement. These attitudes are found to differ sharply according to country, with the Americans most strongly opposed and the Britons most accepting. Multiple regression techniques are used to address the relative importance of socio-demographic and political ideological factors in predicting attitudes toward compulsory retirement. The strongest socio demographic predictor is education. Measures of political ideology are also significant predictors; that is, acceptance of government intervention in various areas of the labor market is positively related to the acceptance of government regulation of retirement age. PMID- 7875915 TI - Education, gender, and the compression of morbidity. AB - According to the Compression of Morbidity (CM) hypothesis, people who exercise, eat nutritiously, do not smoke, and maintain good weight, i.e., people who practice healthy habits, will be more likely to live free of disabling diseases and injuries up until the last few months or years of life. The Increasing Misery (IM) hypothesis, on the other hand, holds that preventive health measures will extend life expectancy but will also increase the number of infirm years. The CM theory implies that curves of morbidity or disability with age should become increasingly "rectangular" for groups who practice healthy habits in the broadest sense. The IM theory does not. This Rectangularization hypothesis is examined with cross-sectional data measuring disability from the Epidemiological Follow-up to the National Health and Nutrition Examination Survey, I (NHEFS), using years of schooling as the independent variable proxy representing favored health status, and examining interactions with age. A modified version of the Disability Index (DI) from the Stanford Health Assessment Questionnaire (HAQ) is used to measure disability. In some analyses, deceased subjects were assigned the worst disability score. Four subsamples of women and men, fifty years old and over, alive and deceased in 1982-84, were analyzed. Female, and especially male, subsamples which included the deceased provided evidence for the CM hypothesis. Results for the subsamples of those remaining alive in 1982-84 were ambiguous. However, lifetime (over age 50) cumulative disability was 21 to 60 percent less for the more educated than the less educated, depending upon whether deceased were included or excluded. If higher education level is an appropriate surrogate for the effect of good health practices, then extending such practices will result in less, rather than more, lifetime disability. PMID- 7875916 TI - A study of stairs in the housing of independently-living elderly people. AB - This survey study focuses on stairs in the homes of a substantial number of independently living elderly (60+) residents of a community in which there are mostly multistory houses and apartment buildings with stairs. While the majority could climb their stairs without problems, a substantial minority lived with stairs despite difficulty and even inability in climbing them. Most people were satisfied with their homes, and many were unwilling to admit that stairs were a present or potential problem. Most people, including most with stair problems, had no plans to move from their homes, however, a majority was willing to concede under questioning that stair-free living in a presently unplanned next home would be desirable. There is a plea that stairs be of increased concern in the housing of elderly people, and that there be increased planning for stair-free homes. PMID- 7875917 TI - Personality traits as determinants of burden and health complaints in caregiving. AB - This study tested predictions specifying the influence of caregiver personality traits on negative outcomes of caregiving, health complaints and burden. Two hundred and thirteen caregivers, who were caring for family members with dementia, were interviewed and their relatives were assessed on cognitive status and aggression. At follow-up conducted twenty-four months later, forty-five caregivers were still continuing to provide home care for their dependents. Caregivers who scored higher on a measure of neuroticism experienced higher levels of burden and health complaints both at initial and follow-up assessment. Caregiver extraversion-introversion did not influence the experience of caregiving. At both initial and final assessment, the ability to enjoy some aspects of caregiving, recreational activities, and satisfaction with social support from family and friends mitigated negative outcomes of caregiving, while appraising the dependent as more troublesome increased negative outcomes. Caring for more cognitively impaired and more aggressive dependents and being female increased negative outcomes initially. Personality traits and most other study variables demonstrated significant continuity across time for caregivers continuing home care. PMID- 7875918 TI - Fluctuations in hypnotic susceptibility and imaging ability over a 16-hour period. AB - Within-subject variability for hypnotic susceptibility as measured by the Harvard Group Scale of Hypnotic Susceptibility, Form A and for imaging ability as measured by the Vividness of Visual Imagery Questionnaire was determined over a 16-hour period. Half of the subjects were day persons, those most alert during daytime hours (as determined by the Alertness Questionnaire); the remaining subjects were night persons. For day persons, hypnotic susceptibility was greatest at 10:00 a.m. and 2:00 p.m.; for night persons, susceptibility was greatest at 1:00 p.m. and between 6:00 p.m. and 9:00 p.m. Imaging ability also varied as a function of time of administration. However, these peak periods occurred before and after hypnotic susceptibility peaks. Such a pattern was interpreted as indicating the possible existence of an ultradian cycle for imaging ability. PMID- 7875919 TI - Hypnotizability and mental imagery. AB - Two studies investigated the relationship between mental imagery and hypnotizability, with the imagery measures administered in a hypnotic context. The correlation of hypnotizability with vividness of imagery was significant in one study, but not in the other; both correlations were significantly lower than that obtained between hypnotizability and absorption, assessed in the same samples. The correlations with control of visual imagery, and with various measures of the vividness of motor imagery, were even lower and rarely significant. Except for an aggregate index of motor imagery, a search for significant nonlinear relationships with hypnotizability yielded nothing that was consistent across studies. Future studies of imagery and hypnotizability should make use of better measures of vividness of mental imagery and consider the relevance of aspects of imagery other than vividness. PMID- 7875920 TI - Hypnotic analgesia, expectancy effects, and choice of design: a reexamination. AB - Previous research by Stam and Spanos suggests that if waking analgesia is followed by hypnotic analgesia, subjects refrain from maximally responding during the waking trial so they report less pain under hypnosis (i.e., a "holdback effect"). This hypothesis was re-examined using more stringent controls. Thirty six highly susceptible subjects chosen by a combination of the Harvard Group Scale of Hypnotic Susceptibility, Form A and the Stanford Hypnotic Susceptibility Scale, Form C were randomly assigned to one of three treatment groups (waking analgesia followed by hypnotic analgesia, waking analgesia followed by waking analgesia, or hypnotic analgesia followed by waking analgesia). Each group received three 60-second immersions of cold pressor pain stimulation (baseline, Immersion 1, Immersion 2) and rated pain using a magnitude estimation and a category rating scale. The obtained results failed to support the hypotheses of a holdback effect or a "reverse-order holdback effect." Properties of within subjects and between-subjects designs were considered in explaining the superiority of hypnotic analgesia over waking analgesia typically found in within subjects models. PMID- 7875921 TI - Emotional self-regulation therapy for smoking reduction: description and initial empirical data. AB - Self-regulation therapy (Amigo, 1992) is a set of procedures derived from cognitive skill training programs for increasing hypnotizability. First, experiences are generated by actual stimuli. Clients are then asked to associate those experiences with various cues. They are then requested to generate the experiences in response to the cues, but without the actual stimuli. When they are able to do so quickly and easily, therapeutic suggestions are given. Studies of self-regulation therapy indicate that it can be used successfully to treat smoking. PMID- 7875922 TI - Modifying hypnotizability: a new component analysis. AB - The effects of the Carleton Skills Training Program (CSTP) on hypnotizability were compared to those of a modified training program in which instructions for physical enactment of the response were omitted. After training, subjects in the original CSTP reported an increase in the extent to which they intentionally enacted suggested behaviors. In contrast, subjects in the modified training program reported increased fantasy without voluntary physical enactment. Nevertheless, both training programs increased behavioral and subjective responsiveness to suggestion, and there were no significant differences in response enhancement between the two programs. Across conditions, increases in behavioral and subjective responses to suggestion were correlated with increased use of fantasy. In contrast, increases in enactment were correlated only with compliance. The modified training program is recommended as a means of enhancing suggestibility with less likelihood than the original CSTP of engendering compliance. PMID- 7875923 TI - Will robots ever replace attendants? Exploring the current capabilities and future potential of robots in education and rehabilitation. AB - This article describes the current capabilities and future potential of robots designed as supplements or replacements for human assistants or as tools for education and rehabilitation. A number of researchers have developed and tested a variety of robot assistants for individuals with disabilities. These robots can usually be classified as educational, vocational or independent-living assistants. Robots in all three categories are reviewed. A brief summary of the critical characteristics of human service robots is also presented and the limitations of current technology are discussed. Finally, current research aimed at addressing these limitations is described. White robots of all kinds have proven much more difficult to develop than people had expected, we conclude that it will eventually be possible to create an effective, reliable robot for human service tasks, but not as quickly as was predicted in the early 1980s. PMID- 7875924 TI - Coping with illness and coping with handicap during the vocational rehabilitation of physically handicapped adolescents and young adults. AB - Coping with illness and coping with handicap during the vocational rehabilitation of physically handicapped adolescents and young adults are given great consideration in rehabilitation centres. The mutual dependence of defence styles and ways of coping with serious illnesses are demonstrated in case vignettes 1 and 2. Defence processes can block coping with illness. In adolescents who are physically handicapped since birth, other body and self-representations are developed according to the form of handicap. After an accident or illness in later childhood or adolescence, new body and self-representations have to be built up in a way that corresponds to the changed physical circumstances (case vignette 3). This is often a lengthy and painful process of mourning. The extent to which the adolescent patient will be granted independence and autonomy from the family will influence the course of the illness itself. The dangers and prospects of lengthy rehabilitation processes are discussed. The necessary adjustments that physically handicapped adolescents have to make when they are admitted into a residential facility for the physically handicapped are described. PMID- 7875925 TI - Psychosocial outcome following severe closed head injury. AB - A comprehensive study of outcomes following severe head injury must clearly include an indicator of psychosocial outcome. Several studies have identified the chronic social isolation which is commonly experienced among this group of people. The present study sought to explore the availability and adequacy of social support following traumatic injury and the relationship between this and emotional distress. In an attempt to identify those sequelae which may be specific to brain trauma, the study compared a group of men with severe head injuries, and their partners, with a group of men with spinal cord injuries, and their partners (n = 60). Time since discharge ranged from 4 months to several years. All four groups reported low availability and adequacy of social integration and exhibited high levels of depression, with no relationship between depression and the length of time since discharge. No statistically significant differences were found between the groups, indicating that the social isolation which has previously been identified amongst people with head injuries may not be attributable solely to brain damage. It would also appear that the repercussions of a traumatic injury extend long after discharge from hospital and this may demonstrate a need to re-examine the provision of service to these client groups. PMID- 7875926 TI - Determinants of time lost from workplace injuries: the impact of the injury, the injured, the industry, the intervention and the insurer. AB - Data from the WorkCover Authority of New South Wales (NSW), Australia pertaining to all injured workers who had at least 1 week time lost from work due to a workplace injury or illness from the health, manufacturing and retail industries in the Newcastle and Hunter regions of New South Wales, Australia, between 1 July and 31 December 1992, were analysed via a series of multiple regression analyses, to determine the relative impacts of injury, worker and organizational factors on the amount of time lost from a workplace injury or illness. The results indicated that the injury variables accounted for 28% of the variance in amount of time lost, and worker variables contributed a further 34% bringing the total explained variance to 62%. Insurer type, employer size and referral to an accredited rehabilitation provider also contributed to the amount of time lost after controlling for both injury and worker characteristics. The roles of worker characteristics, insurer type and accredited rehabilitation providers in time lost need further investigation. PMID- 7875927 TI - The demand, supply and provision system of the rehabilitation technology market in Europe: a modelling perspective. AB - Modelling of the rehabilitation (assistive) technology (RT) market, as introduced in this paper, facilitates a multi-disciplinary and formal analysis of the RT domain, by identifying and interrelating the appropriate abstract entities whose value and relevance are widely appreciated. In particular, three notions are explored, namely, the demand for RT goods, the provision system and the supply of RT goods. Demand and supply are modelled in terms of the key elements which can be extracted from the environment of a demand-related or a supply-related actor respectively. The provision system, on the other hand, is analysed adopting a systems approach, being considered as a complex 'human activity system' whose functional purpose can be described in terms of a dynamic interaction between the field actors, the activities they engage in and the relevant set of factors which affect the system's behaviour. PMID- 7875928 TI - Videotelephony for two persons with moderate mental retardation. PMID- 7875929 TI - A multi-dimensional communication programme for a residential group of severely mentally handicapped women. PMID- 7875930 TI - Employment measures for persons with disabilities in Japan: recent developments. PMID- 7875931 TI - Further studies into the Boc/solid-phase synthesis of Ser(P)- and Thr(P) containing peptides. AB - The Ser(P)-containing peptide corresponding to phospholamban 11-19, Ac-Ala-Ile Arg-Arg-Ala-Ser(P)-Thr-Ile-Glu-NH2, was prepared by the use of Boc-Ser(PO3Ph2)-OH in Boc/solid-phase peptide synthesis followed by HF cleavage of the peptide from the polystyrene resin and subsequent platinum-mediated hydrogenolytic cleavage of the phenyl phosphate groups. A study of the HF deprotection step showed that extensive dephosphorylation of the Ser(PO3Ph2)-residue occurred using three commonly used HF conditions and gave rise to large quantities of the Ser containing peptide. The subsequent study of model peptide systems under standard HF conditions established firstly that the extent of dephosphorylation was dependent on the HF-contact time, and secondly that the Ser(PO3Ph2) residue underwent dephosphorylation at a slightly higher rate than the Thr(PO3Ph2) residue. PMID- 7875932 TI - Conformational investigation of alpha, beta-dehydropeptides. Part VI. Molecular and crystal structure of benzyloxycarbonylglycyl-(Z)-dehydrophenylalanine. AB - The structure of a peptide containing C-terminal dehydrophenylalanine, Z-Gly-(Z) delta Phe (C19H18N2O5, MW = 354) was determined from single-crystal X-ray diffraction data. Needle-shaped crystals were grown from a 1:1 mixture of methanol-acetone in the monoclinic space group P2(1) with a = 14.717(4), b = 4.941(2), c = 12.073(4) A, beta = 103.72(4) degrees; V = 852.86(8) A3, Z = 2 and Dc = 1.32 g cm-3. The structure was solved by direct methods using SHELXS-86 and refined to a final R-index of 0.032 for 1714 observed reflections. The peptide adopts a conformation folded at the glycine residue, and principal torsion angles are omega 0 = -167.6(2) degrees, phi 1 = -71.8(3) degrees, psi 1 = -31.6(4) degrees, omega 1 = -165.7(3) degrees, phi 2 = 65.6(4) degrees, psi 1(2) = 174.4(3) degrees and psi 2(2) = 5.2(4) degrees. Two intermolecular hydrogen bonds, N1-H...O0' and O2-H...O1', join the folded molecules into columns and link columns to each other, respectively. FTIR spectroscopy shows the presence of three hydrogen bonds. This third one has been interpreted as an intramolecular hydrogen bond of the N2-H...N1 type. PMID- 7875933 TI - Methylation in positions 1 and 7 of angiotensin II. A structure-activity relationship study. AB - Six analogues of angiotensin II (Ang) were synthesized with modifications in positions 1 and 7. The study was undertaken in order to learn more about the influence of alkylations in positions 1 and 7 and their interdependence. Previous studies have shown that alpha, alpha-dimethylation of Gly (aminoisobutyric acid, Aib) in position 1 produces quite potent analogues, as does N-methylation of Gly (sarcosine). Combination of both C alpha- and N alpha-methylations to N-Me-Aib1, however, did not produce an affinity increase. Decyclisation of the Pro7-residue produced moderately active analogues with position 7 N-methylation and inactive analogues if the N-alkylation was suppressed. In order to investigate a possible stereochemical interdependence of positions 1 and 7, a group of peptides with combinations of position 1 and 7 alkylations were investigated. The following analogues were prepared: [Sar1,Aib7]Ang, [Sar1,Aib,Leu8]Ang, [Aib1,7,Leu8]Ang, [Aib1,7,Leu8]Ang, [N-Me-Aib1,Aib7]Ang, [N-Me-Aib1,Aib7,Leu8]Ang. They were synthesized by classical solid phase synthesis using the BOC-TFA-HF scheme. The biological properties of these peptides were assessed on the rabbit aorta preparation and their binding potencies were measured on bovine adrenal membranes. Both on agonistic and antagonistic [Leu8]Ang analogues single Aib substitutions in position 1 or 7 induced affinity reduction in both bioassays. Simultaneous Aib modifications in positions 1 and 7 induced more important affinity loss in a synergic manner in both bioassays and as well for agonists and antagonists. The N-Me-Aib1 modifications induce similar affinity loss with or without concomitant Aib7 modification.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875934 TI - Coupling constants and hydrogen bonds as experimental restraints in a distance geometry refinement protocol. AB - A refinement procedure commonly used after distance geometry calculations has been modified to include the use of experimental restraints from coupling constants and hydrogen bonds. Fewer experimental distance constrains (NOEs) are available for peptides as compared to proteins; therefore it is important to incorporate other conformational restraints into refinement methods. The procedure was applied to a cyclic hexapeptide containing two thioamide substitutions, cyclo(-Gly1-Pro2-Phe3 psi [CS-NH]Val4-D-Phe5-Phe6 psi [CS-NH]-). Distance geometry was used to study this peptide, since no potential energy parameters, required in molecular mechanics or dynamics calculations, are available for the thioamide. This is a general problem in the study of peptidomimetics; physiochemical properties of heteroatoms are required within a self-consistent force field. Here, we illustrate the use of metric matrix distance geometry followed by refinement with distance and angle driven dynamics (DADD). We also introduce a new way to handle intramolecular hydrogen bonds by an additional very small and flexible restraint. This method is a viable alternative for the conformational examination of peptides and peptidomimetics. The modifications described here should also find use in the conformational determination of flexible regions of proteins, where the number of NOEs are limited. PMID- 7875935 TI - Migration of monocytes in the presence of elastolytic fragments of elastin and in synthetic derivates. Structure-activity relationships. AB - YGVG and GLVPG, two new chemokinetic peptides, were identified in elastolytic digests of elastin, besides the known chemoattractant hexapeptide VGVAPG. In order to identify possible sequences responsible for the chemotactic and chemokinetic activities and to obtain structure-activity relationships we synthesized some analogues of these peptides: FGVG (an analogue of YGVG), GVAPG and VGAPG (derived from the hexapeptide by deletion of Val1 or Val3). FGVG has a higher chemotactic activity than YGVG (chemotactic indices of 0.62 and 0.49, respectively, at 10(-11) M) and is both chemotactic and chemokinetic. Checkerboard analysis demonstrated that both peptides derived from the hexapeptide present, in addition to the chemotactic activity, a chemokinetic activity. The chemotactic index of GVAPG is 0.66 at 10(-10) M, while for VGAPG it is 0.86 at 10(-9) M. These results indicate that the deletion of the N-terminal residue of the elastin chemotactic peptides, VGVAPG and GFGVG, gives rise to chemokinetic activity. CD and NMR studies showed that all peptides are largely unordered in aqueous solution. PMID- 7875936 TI - In vitro cross-linking of calf lens alpha-crystallin by malondialdehyde. AB - The effect of malondialdehyde on structural features of bovine alpha-crystallin has been investigated by absorption and fluorescence spectroscopy as well as by far-UV circular dichroism. Experimental evidence suggests the occurrence of intermolecular cross-linking induced by malondialdehyde. This cross-linking does not seem to affect the tryptophan environment, as suggested by intrinsic protein fluorescence. On the contrary, the time dependence of far-UV dichroic activity indicates that the cross-linking is accompanied by a secondary structure change. The formation of high molecular mass aggregates, evidence by electrophoresis in denaturing conditions, leads to irreversible alpha-crystallin aggregation due to extensive intermolecular cross-linking. Since malondialdehyde is produced in vivo as a breakdown product of lipid peroxidation the possible involvement of this molecule in the pathological mechanism of cataract formation has been briefly discussed. PMID- 7875937 TI - Synthesis and characterization of a new labeled gastrin ligand, 125-I-BH-[Leu15] gastrin-(5-17), on binding to canine fundic mucosal cells and Jurkat cells. AB - In the course of our study concerning gastrin and cholecystokinin (CCK) receptors, we have synthesized and characterized a new labeled gastrin ligand, 125I-BH-[Leu15]-gastrin-(5-17) [(3-[125I]iodo-4-hydroxyphenyl)-propionyl-[Leu15] gastrin-(5-17)]. Binding of 125I-BH-[Leu15]-gastrin-(5-17) to isolated canine fundic mucosal cells was specific, saturable and of high affinity. 125I-BH [Leu15]-gastrin- (5-17) and 125I-BH-CCK-8[(3-[125I]iodo-4-hydroxyphenyl) propionyl-CCK-8] interact with isolated canine fundic mucosal cells with small differences in maximal binding capacities and affinities, 3800 +/- 900 binding sites/cell (Kd = 0.52 +/- 0.23 nM) and 6200 +/- 1100 binding sites/cell (Kd = 0.31 +/- 0.18 nM), respectively. The relative order of potencies for gastrin and CCK analogs in displacing 125I-BH-[Leu15]-gastrin-(5-17) binding correlated well with those obtained using 125I-BH-CCK-8. Selective CCK/gastrin antagonists L 364,718 (MK-329) and L-365,260 also inhibited 125I-BH-[Leu15]-gastrin-(5-17) binding. These results indicate that 125I-BH-[Leu15]-gastrin-(5-17) binds to gastrin receptors in isolated canine fundic mucosal cells. We have also characterized 125I-BH-[Leu15]-gastrin-(5-17) binding to the human Jurkat lymphoblastic cell line (Jurkat cells) known to express the CCK-B/gastrin receptor. Saturation experiments have shown that both 125I-BH-[Leu15]-gastrin-(5 17) and 125I-BH-CCK-8 interact with a single class of high-affinity binding sites in the Jurkat cell line.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875938 TI - The conformational stability of a non-covalent dimer of a platelet-derived growth factor-B mutant lacking the two cysteines involved in interchain disulfide bonds. AB - Native platelet-derived growth factor-B (PDGF-B) forms a covalent dimer through interchain disulfide bonds. In a previous study, an analog of PDGF-B was produced by replacing cysteine 43 and 52, which are involved in the interchain disulfide bonds, with serine. It was revealed that this analog protein has the dimeric molecule weight at pH 4 to 7, forming a non-covalent dimer in solution, and its mitogenic activity is similar to the native covalent dimer. However, the analog protein was more labile to pepsin digestion and low pH treatment, indicating that the interchain disulfides contribute to the stability of the protein. It is interesting to see if the conformation of the protein is affected by elimination of the interchain disulfide bonds, and if the interchain disulfides play any role in the stability of the protein. Circular dichroism and Fourier transform infrared spectroscopic analyses of the analog showed that it has a conformation similar to the wild type at pH 7.5, but is unfolded at pH 2.5, while the native PDGF-B disulfide-linked dimer shows an apparently unaltered conformation at pH 2.5. The analog is also less stable to sodium dodecylsulfate and guanidine HCl induced denaturation at neutral pH. These results indicate that the non-covalent interactions are sufficient for proper folding and dimer formation at neutral pH, but that the interchain disulfide bonds greatly stabilize the native conformation of PDGF-B. PMID- 7875939 TI - Conformational study of cyclosporin A in acetone at low temperature. AB - The conformation of cyclosporin A (CsA), an undecapeptide with seven N-methylated amino acids, was studied in acetone at 193 K. Previous studies of the conformation of CsA in different solvents, in the cyclosporin-cyclophilin complex and in complexes with LiCl showed that the conformation of the free and the bound CsA are different. Differences were observed at the conformation of the MeLeu9 MeLeu10 peptide bond, which is cis in solution and trans in the complex, and in the orientation of the amide protons and the N-Me groups. By using acetone, which is a proton acceptor, we wanted to influence the orientation of the amide protons. In the conditions used in this study a new conformation is found, which differs as well from the one previously observed in solution as from the conformation observed in the complex. This conformation has a cis peptide bond between MeLeu9 and MeLeu10. The trans conformation of the peptide bond MeLeu9 MeLeu10, which is necessary for biological activity, was not induced. One of the amide protons is involved in an intramolecular H-bridge stabilising a beta-turn around Sar3MeLeu4, and three of the seven NMe groups are oriented to the centre of the molecule. PMID- 7875940 TI - Conformational stability of the endothelin/sarafotoxin family of peptides. AB - There are significant differences between the structures reported for members of the endothelin/sarafotoxin family of peptides, but also for the same peptides studied by different groups, raising the possibility that some of the differences are attributable to variation in solution conditions rather than intrinsic structural heterogeneity. We have shown, using circular dichroism spectroscopy and equilibrium sedimentation, that the secondary structures of these peptides are little affected by wide variations in pH, or by self-association. Although acetonitrile has a pronounced effect on the extent of peptide self-association it does not appear to alter the backbone structure of sarafotoxin SRTb, and has only minor effects on endothelin-1 and endothelin-3. The observed conformational variation thus appears largely to reflect sequence-dependent differences. PMID- 7875941 TI - Turn induction by N-aminoproline. Comparison of the Gly-Pro-Gly and Gly psi [CO NH-N]Pro-Gly sequences. AB - The folded structure induced by the N-aminoproline residue (the hydrazino analogue of proline, denoted hPro) in the Boc-Gly1-hPro2-Gly3-NHiPr hydrazino tripeptide has been characterized in the solid state by X-ray diffraction, and compared to the usual beta II-turn structure in the Boc-Gly1-Pro2-Gly36-NHiPr cognate tripeptide. It is stabilized by a bifurcated hydrogen bond in which (Gly3)NH interacts with both (Gly1)CO and (hPro2)N alpha. This conformation is retained in CH2Cl2 and CHCl3 solutions, and allows an overall folded conformation of the hydrazino tripeptide in which (iPr)NH is hydrogen-bonded to (Boc)CO. The hPro alpha-hydrazino acid residue appears to promote a local folded structure, and might behave as a beta-turn mimic. PMID- 7875942 TI - 1H NMR analysis of fibril-forming peptide fragments of transthyretin. AB - Peptide fragments of the protein transthyretin, previously shown to form cross beta-sheet amyloid-like fibrils in vitro, were investigated using 1H 1D and 2D NMR techniques. TTR 10-20, TTR 105-115 as well as a substituted analogue, (TTR 105-115Met111) all formed amyloid-like fibrils readily in 20-30% acetonitrile/water at room temperature. It was found that the presence of fibrils in the peptide solutions did not affect the observable NMR spectra, which may have been due to the line-broadening that would be associated with these macromolecular species. 1H NMR spectra were thus representative of the monomeric form of the peptide in solution. Information from D2O exchange, 3JNH-alpha H coupling measurements, temperature coefficients and NOESY experiments suggested that these peptides have some propensity for turn or helix but were predominantly unstructured. There was no indication of the monomeric species existing predominantly in an extended form, suggesting that the formation of beta-sheet based fibrils does not require preformed extended structures. TTR 105-115Met111 displayed slight structural differences from TTR 105-115 which may be related to the fibril-forming propensity of the corresponding mutant TTR. PMID- 7875944 TI - Investigative Ophthalmology and Visual Science, annual meeting. Fort Lauderdale, Florida, May 14-19, 1995. Abstracts. PMID- 7875943 TI - Sometimes it is neither a racemisation nor an epimerisation but an enantiomerisation. A plea for preciseness in the use of terms describing stereomutations that occur in peptide synthesis. PMID- 7875946 TI - Perceptions on occupational satisfaction among Iowa dentists. PMID- 7875945 TI - Infant dental health--the first visit. PMID- 7875947 TI - The role of mental health professionals in mass casualty events. PMID- 7875948 TI - Psychological aspects of developmental endocrinopathies in adolescence. AB - Ninety-six adolescents referred to a pediatric endocrinology clinic were divided into eight groups according to degree of sexual maturity and height. Each adolescent was assessed by a psychiatric interview, a self-concept questionnaire, a human figure drawing test and a cognitive screening battery. The results showed a definite deleterious effect of growth retardation, but not sexual maturity, on self-concept. Sex of the adolescent did not affect the results. Cognitively there was no difference between groups. The psychological impact of short stature should be taken into consideration in the decision to utilize pharmacological or delay of puberty. PMID- 7875949 TI - Involuntary hospitalization--medical or judicial authority. AB - The case described in this paper is the basis of two verdicts, which are very important case law precedents. These verdicts, given in connection with the new law for the treatment of the mentally ill, clarify the framework in which involuntary hospitalization in Israel is implemented. These verdicts exemplify the shifting of authority, on the issue of commitment, from the medical model to a more judicial one. Although the first step in the commitment system is still performed by a physician (the district psychiatrist), the entire system is now under strict judicial supervision, and the legal procedure is of utmost importance. PMID- 7875950 TI - Jews and their intraethnic differential vulnerability to affective disorders, fact or artifact? I: An overview of the literature. AB - The observation that Ashkenazim have higher rates of affective disorders than either Sephardi or Oriental Jews was reanalyzed from the available literature. Statistical reanalysis of these studies was consistent with rates being elevated for Ashkenazim. The results of these treatment-based studies, however, suffer from biases due to differential help-seeking patterns, lack of accounting for readmission rates, diagnostic unreliability, misuse of frequency ratios relative to other disorders and failure to control for confounding variables. As a result of these causes for biases and in the absence of a true incidence or prevalence study serving as a basis for these observations, the assumption that Ashkenazim are at an increased risk for affective disorders is questionable and may be a mere result of methodological artifacts. PMID- 7875951 TI - Serotonin and suicidality: the impact of acute fluoxetine administration. I: Serotonin and suicide. AB - The general enhancement of central serotonin (5-HT) neurotransmission following long-term administration of serotonin-selective reuptake inhibitors (SSRIs) appears to play an important role in these drugs' anti-depressant efficacy. Because suicide and/or aggression appear linked to diminished levels of brain 5 HT and its metabolites, it has been suggested that SSRIs may be particularly effective in reducing suicidality. Case reports of increased or new suicidal ideation following administration of fluoxetine and other SSRIs, however, raise questions about how these potential side effects may relate to the SSRI's acute effects on 5-HT transmission. Part I of this review examines fluoxetine's effects on suicidality and related behaviors and reviews the relationship of suicidality to serotonergic dysregulation. PMID- 7875952 TI - Developing psychosocial mindedness and sensitivity to mental health issues among primary care nurses using the Balint group method. AB - This study empirically evaluated the impact of a Balint group for primary care nurses on awareness of mental health and psychosocial issues and professional psychosocial efficacy. Thirteen female primary care nurses working in community clinics participated in a year-long fortnightly Balint group led by two psychologists at a regional school of nursing. Cases were presented and analyzed to highlight emotional and cognitive components and processes. Changes in professional psychosocial efficacy were assessed with the Psychological Medical Inventory (PMI). Efficacy components were (a) psychosocial abilities, (b) psychosocial sensitivity. Changes in these components and in perceived mental health topics were assessed over three time points: at initial interview, midway through group and at the end. Significant positive changes were found on both efficacy components at the final measure compared to baseline. This study indicates the beneficial effects of this method in training primary care nurses in psychosocial efficacy. It also highlights the importance of ongoing long-term training programs for mental health and psychosocial efficacy in this professional group. PMID- 7875953 TI - A psychopharmacology education program for psychiatry residents--the role of a clinical pharmacist. AB - The author describes a psychopharmacology education program administered by a psychiatric clinical pharmacist. The program included biweekly lectures and psychopharmacology review rounds for junior psychiatry residents. This teaching program suggests that a psychiatric clinical pharmacist may favorably contribute to the optimum usage of psychotropic drugs, especially in those residency years when prescribing habits are being formed. PMID- 7875954 TI - Body esteem in Israeli university students. AB - Body-esteem is an important dimension in the general concept of body-image. The Body Esteem Scale (BES) was developed and tested in the USA. We tested young men and women in Israel all of whom were university students after their army service. Our results show that Israeli men score lower (feel more negative) on the virility reflecting subscale while Israeli women score higher (feel more positive) in the weight concern subscale--compared to their American counterparts. We discuss the possible explanations of this difference, focusing mainly on the impact of army discharge and the move to the academic field. PMID- 7875955 TI - Reverse intermetamorphosis--a rare misidentification phenomenon. AB - The authors present a case including two variants of delusional misidentification: Fregoli variant and intermetamorphosis. The present case has two interesting aspects: a) intermetamorphosis occurred in the patient himself, rather than in another person; b) the intermetamorphosis was only psychological and not physical. PMID- 7875956 TI - Treatment of the religious patient. PMID- 7875958 TI - Differing patterns of psychiatric impairment in Alzheimer and demented parkinsonian patients. AB - Psychiatric symptoms were investigated and compared in 95 patients with Alzheimer type dementia (DAT) and in 39 patients with Parkinson's disease with dementia (PD D). The diagnosis of the dementia and psychiatric disorders was based on DSM III R criteria; dementia stage was assessed using the Clinical Dementia Rating Scale (CDR). PD-D were significantly older than DAT patients. Delirium was more frequent in the advanced stages of both PD-D and DAT, being mainly of the hypoactive type in PD-D and the hyperactive type in DAT. Delusions and hallucinations predominated in the early CDR stages of both illnesses and did not differ between groups; the same was true for depression. The results revealed different psychopathological profiles in DAT and PD-D patients. PMID- 7875957 TI - Protirelin tartrate (TRH-T) in upper motoneuron syndrome: a controlled neurophysiological and clinical study. AB - This randomised, single-blind, placebo-controlled study involved 20 patients with chronic upper motoneuron syndrome due to ischemic cerebrovascular lesions, selected in order to ensure the greatest possible homogeneity in terms of the severity of the syndrome. All of them were treated with protirelin tartrate 4 mg/die i.m. The study included semiquantitative clinical evaluations of neurological examinations, with particular attention being paid to weakness and spasticity. These were accompanied by neurophysiological evaluations (F-waves, magnetic motor evoked potentials). Extended biohumoral investigations of possible side effects were also carried out. The results indicate a slight but statistically significant absolute improvement in spasticity and muscular strength following protirelin tartrate, especially in the lower limbs; at the same time, the drug also proved to be capable as favourably modifying the response of the biceps femoris muscle to transcranial magnetic stimulation (reappearance, increased amplitude and a reduction in the threshold of motor evoked potentials). The drug was generally well tolerated. PMID- 7875959 TI - Proton magnetic resonance spectroscopy in patients with ischemic stroke. AB - Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive technique which has proved to be useful for monitoring various brain metabolites (N-acetyl aspartate, choline, creatine-phosphocreatine, lactate). A total of 18 patients underwent a combined magnetic resonance imaging (MRI)/1H-MRS protocol in order to evaluate the distribution of the metabolites in the various stages of cerebral ischemia. Our results show a marked decrease of N-acetyl-aspartate and a large content of Lactate during the early phases, and a decrease in N-acetyl-aspartate, choline and creatine-phosphocreatine (Cr-PCr) during the chronic phase. PMID- 7875960 TI - Balloon occlusion of the carotid artery in the treatment of cavernous giant aneurysms: two cases. AB - Over recent years, endovascular occlusion of the carotid artery has become a valid alternative to its more traditional surgical ligation in the treatment of cavernous giant aneurysms. The authors report two cases treated with balloon occlusion in two patients with clinical signs of cavernous sinus syndrome. The procedure consisted of occluding the aneurysm and the carotid by means of detachable balloons. This was preceded by a 30-minute clinically monitored occlusion test aimed at evaluating the functioning of Willis' circle. The treatment was carried out under neuroleptoanalgesia, so optimal control of the neurological condition of the patient was possible. Partial symptom regression was obtained in both cases. PMID- 7875961 TI - Dumbbell-shaped spinal epidural cavernous angioma. Case report. AB - Cavernous angiomas are common lesions of the CNS characterized by abnormally dilated blood vessels lined by a thin endothelium, closely clustered together and not separated by normal neural tissue. They are more frequently found intracranially. In the spine, a common location is the vertebral bodies. Intradural extramedullary and intramedullary cavernous angiomas are less frequent lesions, while purely epidural locations are uncommon. Spinal dumbbell-shaped epidural cavernous angiomas are exceedingly rare, and only six cases have been reported in the literature. We describe one additional case whose MRI appearance was indistinguishable from that of a neurinoma, which is a much more common lesion. Surgical treatment is advised and complete radiological evaluation is necessary to rule out concomitant localizations in other organs. PMID- 7875962 TI - Migrant sensory neuritis associated with AIDS: case report. AB - We studied an AIDS patient who suffered from numbness, paresthesias and pain in the territories of different non-contiguous cutaneous nerves at different times. A transitory partial loss of touch and pinprick sensibility was also present in the same cutaneous areas. Sensory conduction velocities and SAP amplitudes were normal. The clinical picture was consistent with the Migrant Sensory Neuritis of Wartenberg. This rare neuropathy has never previously been described in patients affected by AIDS. PMID- 7875963 TI - Possible predictive parameters for the outcome of bacterial meningitis. PMID- 7875964 TI - [Author, authors, many authors]. PMID- 7875965 TI - [Complications of synthetic hair implantation]. AB - Five men (average age 35 years) suffering from the sequelae of hair implants were examined in the course of claims for legal compensation. Polyether amide hair fibres had been implanted, 1000 per patient and session. In all cases the improved implantation technique with a fine needle and subcutaneous knotting had been used in a total of three institutions. Three patients developed bacterial folliculitis after 4-8 weeks; in the other two patients this developed later, after 3-6 months. In two patients the possible triggering event was the wearing of a motorcycle helmet and a vacation in a tropical climate respectively. In another patient the artificial hair curled considerably after he visited a sauna. The implanted hair had fallen out almost completely in all cases (100% in two patients after 9-12 months, 50-75% in three patients after 7 months to 2 years). All patients showed cosmetically disturbing small scars and pigmentary changes. Despite an apparently improved complication rate, the new technique of hair fibre implantation remains a doubtful procedure and cannot be recommended in view of possible permanent sequelae. PMID- 7875966 TI - [Incidence and increase in type I allergies to rubber gloves in dental medicine students]. AB - The prevalence of type I allergy against latex was investigated in dental students by questionnaire, prick tests and the determination of specific IgE antibodies. Positive prick tests against different latex fluids were found in 18 (8.7%) of 206 students, with clinical relevance in 11 cases. When the total number of students in each semester was taken into account an increase in the minimal prevalence of clinically relevant latex allergy from 2% in the second semester to 10.4% in the tenth semester was seen. A history of glove intolerance presenting as a wheal-and-flare reaction was associated with a type I allergy against latex in only 50% of the affected subjects. Atopic diseases and hand eczema of different causes proved to be risk factors in 16 and 5 of 18 students with latex allergy, respectively. A high-ammonia accelerator-free latex fluid proved to be a very reliable test medium compared to the less sensitive determination of specific IgE antibodies to latex. PMID- 7875967 TI - [Follow-up of cutaneous paradoxical vascular reactions in atopic patients during and after eczema manifestations]. AB - In atopic eczema patients the well-known abnormal cutaneous reactivity of the blood vessels (white dermographism, delayed blanch after acetylcholine, paradoxical blanching after nicotinic acid application and diminished erythema after histamine injection) were observed during acute eczematous episodes and later in an exzema-free state in comparison with controls. In this follow-up study the use of different stimuli allowed us to demonstrate abnormal cutaneous vascular reactions in the patients depending on the severity of their atopic eczema. Severely affected patients showed persistence of the paradoxical vascular reactions even in an eczema-free cutaneous state. PMID- 7875968 TI - [Large cell anaplastic Ki-1 positive lymphoma of the skin. 5 personal cases and review of the literature]. AB - Primary cutaneous large cell anaplastic non-Hodgkin lymphomas positive for Ki-1 antigen are rarely described. There are 100 published cases worldwide. Typically large cell anaplastic lymphomas have an inflammatory appearance, which often leads to false diagnosis and unsuccessful treatment with antibiotics. Histological examination reveals a highly malignant non-Hodgkin lymphoma. The tumour is composed of large pleomorphic lymphoid cells composed of T-cells in 80% of the cases and of B-cells in 10%. The immunological phenotype in the remaining 10% remains unclear. Crucial for the diagnosis is the expression of CD30 antigen in > 70% of the tumour cells. This article presents 5 cases of cutaneous Ki-1 positive lymphoma seen in our Berlin department during the last 10 years. In 4 patients the diagnosis was established in clinical stage I of cutaneous lymphoma without further manifestation; 1 patient had lymph node involvement and was in stage II. Total excision of the primary tumour in stage I with adjuvant polychemotherapy in stages II-IV led to complete remission in all cases. Long term remissions were seen in case 1 (2 years) and in case 5 (1 year), whilst 2 patients showed local relapse, and 1 patient showed generalized lymphogenic and hematogenic metastasis. After repeated surgical removal or irradiation of the tumour and adjuvant polychemotherapy, further complete remission was achieved in 2 patients (up to now lasting 1 and 4 years). another patient has been in partial remission for the last 2 years. Our observations underline the high relapse rate of large cell anaplastic lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875969 TI - [Arterial occlusion in cutis marmorata teleangiectatica congenita]. AB - Cutis marmorata teleangiectatica congenita (CMTC) is a rare congenital vascular disorder of the venous system. In 50% of cases there are associated anomalies of other organ systems. Clinical improvement of the cutaneous manifestations is noted in most cases and usually occurs during the first year of life. We present a patient with CMTC with a band-like pattern following the L3 dermatome. At the age of 13 years, the skin manifestations worsened, with ulcerations and intermittent claudication. Angiographic imaging revealed stenosis of the deep femoral artery, and the circumflex femoral artery and the first perforating arteries were not visualized. To our knowledge, this is the first reported case of CMTC with anomalies of the large arteries. PMID- 7875970 TI - [Modern molecular biology diagnosis of malignant cutaneous lymphomas]. AB - The diagnosis of cutaneous malignant lymphoma is based on clinical, histo morphological and immunochemical findings and, now a days, on molecular biology analyses of the genotype in the lymphocytic infiltrate. By using the polymerase chain reaction (PCR) with specific primers for the Ig heavy chain gene and the T cell receptor gamma chain gene, the detection of monoclonal cell populations in the skin infiltrate is possible. Since this method produces results within 3 days, since paraffin-embedded skin and lymph node biopsies and heparinized peripheral blood can be used and since no radioactivity is necessary, this technique has important advantages over traditional techniques such as Southern blot analyses. In addition, specific PCR analyses may allow a patient-specific monitoring during therapy and also may detect early relapses of the lymphoproliferative malignant disease. PMID- 7875971 TI - [Anaphylaxis caused by latex contamination from the wrapper of the cannula plaster]. AB - A patient with pronounced latex allergy was admitted to hospital because of suspected drug allergy. He developed an anaphylactic reaction manifesting with skin reactions and difficulties in breathing immediately after an intravenous cannula was applied, although the doctor was wearing latex-free gloves. The envelope of the plaster with which the cannula was fixed was found to be the source of the latex responsible for the anaphylactic reaction. Latex contact with the skin was due either to latex contamination of the doctor's hands when opening the envelope or to the plaster itself. The case report demonstrates the difficulties arising both from the clinical reaction pattern of type I reactions to latex and from strict avoidance of latex-containing products and points out the necessity of latex declaration. PMID- 7875972 TI - [Pre-myopathic versus amyopathic dermatomyositis. 2 personal cases and review of the literature]. AB - The so-called amyopathic dermatomyositis is a rare variant of dermatomyositis which has attracted increasing interest during the last years. One finds the classical signs of dermatomyositis such as periorbital edema and erythema, erythematous macular and papular lesions localized at bony prominences (so-called Gottron's papules), generalized pruritus, photosensitivity, and a cutaneous histopathologic picture compatible with skin lesions of dermatomyositis. Crucial for the diagnosis is the exclusion of myositis by clinical examination, EMG and histology. Furthermore, longterm supervision of patients is advisable in order not to miss the appearance of early signs of myositis. The longest reported follow-up of amyopathic dermatomyositis patient is 4 years; however, it cannot be excluded that these cases will eventually culminate in classical dermatomyositis. In this paper we describe two cases and discuss the differential diagnosis and therapy; also, the term "Premyopathic dermatomyositis" is proposed, to indicate that the full picture is to be expected in most cases. PMID- 7875973 TI - [Congenital onychodysplasia (Iso-Kikuchi syndrome)]. AB - A 1-year-old girl shows changes of the toenails since birth. There are no associated anomalies typical for genodermatoses, nor is there a family history of this disorder. Physical examination shows missing or incomplete toenails. In addition a shortening of the second toe on both sides and the third toe on the left side is found. The second and third toe on the left side shows incomplete syndactylia. The fingers and fingernails are all normal. Isolated congenital onychodysplasia of the toenails has not been previously reported. PMID- 7875974 TI - [Workshop of the Flow Cytometry Study Group of the Society of Dermatologic Research 08 September 1993 in Bonn. Protocol and author index]. PMID- 7875975 TI - [Laparoscopic Y-Roux anastomosis]. AB - In order to circumvent laparotomy in patients with biliary obstruction due to inoperable carcinoma of the pancreatic head, we evaluated the feasibility of a bypass operation using minimal invasive measures. A technique of laparoscopic cholecystojejunostomy was developed in adult pigs with a previous clip occlusion of the distal common bile duct to imitate choledochal obstruction. Complete biliary bypass was restored with a cholecystojejunostomy via a Roux-en-Y loop using two circular staplers (21, 25 or 29 mm diameter), introduced through a 33 mm-diameter trocar, to perform the proximal and distal anastomoses. 12 pigs operated in this way, recovered easily with normal weight gain and without technical complications. Contrast radiography of the biliary bypass at autopsy on day 28 demonstrated patent and leak-free anastomoses and functional bypass. We conclude that laparoscopic cholecystojejunostomy with Roux-en-Y loop is a feasible technique resulting in an uncomplicated postoperative course and a biliary bypass with optimal function. Endoscopic application of circular staplers to perform laparoscopic entero-biliary and entero-enteral anastomosis is practical and safe. PMID- 7875976 TI - [Lymphocele after kidney transplantation: drainage by laparoscopy]. AB - Our video shows the laparoscopic drainage of a big lymphocele responsible of kidney graft obstructive failure. Apart from the laparoscopic access, the technique is similar to open surgery. An ellipsoid peritoneal window (approximately 6 x 3 cm) is created with scissors and electrocautery. The lymphocele is entered and completely drained. A few adhesions are divided. To keep the window open, we secured its anterior margin with clips. Postoperative period was uneventful, with immediate improvement of the kidney graft function. After 4 months, there was no lymphocele seen on computerized tomography. PMID- 7875977 TI - [Video-endoscopic surgical technique in established thoracoscopic interventions]. AB - The video shows six different established thoracoscopic interventions besides the treatment of spontaneous pneumothorax. Adhesiolysis (1) is demonstrated in a patient with malignant pleural effusion, followed by palliative pleurodesis by talkage (2). Resections of benign extra- (3) and intrapulmonary (4) tumors are shown as well as endoscopic pericardial fenestration (5) and thoracic sympathectomy (6). PMID- 7875978 TI - [Surgical technique in vascularized auto- and allotransplantation of the knee joint in a dog model]. AB - Experimental transplantation of vascularized canine knee joints has so far been associated with high complication rates in both auto- and allografts. We have now compared 4 autografts and 4 allografts that were successfully performed at our institution. This report details our surgical technique. Stable internal fixation enabling immediate postoperative weight bearing, microsurgical end-to-end anastomoses of popliteal artery and vein and postoperative control of immunosuppression in transplanted animals are crucial. Thus, an interdisciplinary approach of experts in microsurgery, orthopedic and trauma surgery and immunologists appears to be a prerequisite for successful joint transplantation. PMID- 7875979 TI - [Risk and prevention of HIV infection in the operating room]. PMID- 7875980 TI - The management of intestinal fistulae. PMID- 7875981 TI - [Role of the surgeon in the team and in hospital administration]. PMID- 7875982 TI - [The clinic as profit center and management with reference figures]. AB - Financial responsibility is one of the important aspects of hospital management. At the hospital of Uster a trial with a profit center concept was started in October 1991. This concept included development of management tools such as reference figures to check costs, returns and performance. Thus it was possible to obtain an equilibrium between personnel costs and performance within 6 months. In the first half of 1993 the budgeted performance figures for 1993 have so far been reached. Although a complete implementation of a profit center concept in a public hospital does not seem possible, a profit center-like structure helps to obtain financial control and enables the hospital management to readily adapt to changing conditions. PMID- 7875983 TI - [Vascular injuries. Diagnosis and technical procedure]. AB - Fractures complicated by vascular trauma are rare but very complicated injuries. Clinical diagnosis is confirmed by Doppler sonography and/or arteriography. Time effectiveness in investigation and therapy is most important, cooperation between orthopedic and vascular surgeons is crucial. If indication is correct, arterial reconstruction has excellent results in these severe injuries. PMID- 7875984 TI - [Integration and resorption of calcium phosphate ceramics in defect filling of fractures of the tibial head. Radiologic long-term results]. AB - Calciumphosphate ceramics are considered as a substitute for cancellous bone grafts. 16 patients with traumatic impressions of the tibial plateau were treated according to the AO-principles and subchondral bone defects were filled with hydroxyapatite (10x) or tricalciumphosphate (6x). Clinical and radiological follow-up after 3 to 10 1/2 years was uneventful with primary bone healing and excellent results in all cases. No adverse reactions of the completely integrated ceramics have been observed. Hydroxyapatite, even after 10 years, showed no proof of biodegradation, whereas tricalciumphosphate showed slow dissolution and replacement by new host bone formations in the later follow-up after 2 to 6 years. PMID- 7875985 TI - [Principles for treatment of open fractures]. AB - Fractures with soft-tissue injury are urgent surgical emergencies. Fracture care in the first few hours after the injury crucially determines the course of healing. In open fractures aggressive debridement of all necrotic tissues is mandatory as well as stable external or internal fracture fixation. Secondary wound closure must be performed liberally and prophylactic antibiotics should be administered. Closely observing such a stringent regimen, the rate of posttraumatic osteitis in open fractures can be reduced significantly. PMID- 7875986 TI - [External fixator: surgical technique, pinless fixator, change in procedure]. AB - External Fixation-Technique: The advantages of external over internal fixation are as follows: a) endosteal and periosteal blood supply is undisturbed, b) "low tech" equipment may be used, c) secondary adjustments are possible and d) easy implant removal. These benefits however are outweighed by the main disadvantages of long term external fixation i.e. pin complications and delayed union of fractures. Better understanding of postoperative management and careful application of screws of improved design will lead to better results. Today's standard applications of external fixation for tibial fractures is a unilateral fixator, using Schanz screws. The pin-bone interface is the most critical site of all external fixation. By avoiding heat necrosis (low temperature drilling) and preventing micro motion at the pin-bone interface (by applying bending- or more recently radial-preload), pin complications such as infection and loosening can be reduced. Two Schanz screws are inserted into each main fragment and are connected with one short tube per fragment. The fracture is then reduced by using these tubes as handles. After reduction a third tube connects the first two by means of two tube-to-tube clamps. This type of fixation will easily allow for three dimensional secondary corrections of alignment. Approximately three weeks following the injury some motion at the fracture site will stimulate callus formation. This can be achieved by destabilisation, dynamisation or "active stimulation" of the fracture site [2]. Pinless fixator: The pinless external fixator holds the fragments firmly with pointed clamps that penetrate about one millimeter into cortical bone without entering and contaminating the medullary canal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875987 TI - [Effects on the superior urinary tract caused by urinary diversion]. PMID- 7875988 TI - [Rhabdomyosarcoma of the prostate and bladder in a child: radical or conservative surgery?]. AB - Rhabdomyosarcoma is the most common soft-tissue tumor in childhood. In infants it is frequently localized in the pelvis and in the prostata or bladder region. The aim of treatment should be to eradicate the tumor and yet maintain as normal function as possible. Effective preoperative chemotherapy has enabled one to frequently achieve this aim. We report on two patients both with a rhabdomyosarcoma of the bladder-prostata. One of them in 1983 was operated and treated with chemotherapy and cysto-prostatectomy and the other in 1991 with chemotherapy and eradication of the tumor without cystectomy. Both children are now tumor-free after 10 years/2 years resp. Both approaches are discussed. PMID- 7875989 TI - [Endoscopic lithotripsy with the Swiss lithoclast. Apropos of 168 cases]. PMID- 7875990 TI - [Retrograde ureteroscopy and treatment of ureteral lithiasis with the lithoclast]. PMID- 7875991 TI - [Tumor induction in intestinal urinary reservoirs]. PMID- 7875992 TI - [Squamous epithelial carcinoma of the kidney pelvis--a rare tumor]. PMID- 7875993 TI - [Primary detection of malignant mesothelioma of the tunica vaginalis testis using the BMA-120 monoclonal antibody]. AB - Malignant mesothelioma of the tunica vaginalis testis is an extremely rare tumor, with only 40 cases previously described in the literature. Treatment consists of inguinal orchiectomy with close-follow up [1]. Asbestose exposure, trauma and hydrocele have been implicated as risk factors. We describe a histopathological examination with the BMA antibody (Behring, Marburg, Germany) and the Lu-5 antibody (Hoffmann-La Roche, Basel, Switzerland). Furthermore, we describe the patient's history and the management according to preceding reports in the literature. PMID- 7875994 TI - [Bile duct carcinoma after abdominal irradiation for urologic malignancies]. AB - Malignancies of the biliary tract are rare diseases. Tumor inductions after radiotherapy are reported in several papers. We report about 3 cases with consecutive biliary tract carcinoma 18-32 years after manifestation of an urogenital carcinoma. All 3 patients (52-63 years) were treated with additive radiotherapy after surgical-urological therapy. Icterus was the top-ranging symptom of this secondary carcinoma. In 2 of the 3 cases surgical tumor resection was performed (biliary duct resection with central liver resection; pancreatico duodenectomy). Because of the bad general condition of health the third patient got only a biopsy of the tumor. All patients died within 2 years after diagnosis. The accidental accumulation of the rare biliary tract carcinoma after urogenital malignancies in our collection of clinical cases (2 seminoma; 1 bladder tumor) give rise the question about the causal association between primary carcinoma, additive therapy and the development of secondary carcinoma. PMID- 7875995 TI - [Emergency bypass operation after failed elective percutaneous transluminal coronary angioplasty]. AB - This retrospective study was performed to evaluate the clinical and angiographic characteristics and the in-hospital complications after failed percutaneous coronary angioplasty (PTCA) that necessitates coronary artery bypass graft surgery (CABG). The study population consisted of 123 patients from January 1990 to December 1992. The failed PTCA was secondary to an acute occlusion of the dilated but dissected vessel in 36.5% of the study population. 43 patients (35%) had an emergency CABG due to hemodynamic instability and a large area of myocardium at risk for infarction. 93% of these patients had an acute closure of the dissected vessel. 19 patients (15%) were operated 24 hours after failed PTCA and 61 patients (49.5%) electively 3.8 +/- 1.1 months after PTCA. Mean time interval from the acute occlusion up to the establishment of the extracorporeal circulation (ischemic interval) was 70 +/- 9 min. in patients from our cardiological department and 136 +/- 14 min. in patients from external departments. Analysis of the surgical data revealed that neither a patient of the emergency group nor of the elective group needed the intra-aortic balloon pump. Overall 2.3 +/- 0.8 bypass grafts were placed, with increased use of the internal mammarian artery in the elective (57%) versus the emergency group (17%). Postoperative peak values of CK and CK-MB were significantly higher in the emergency group as compared to the patients operated 24 hours and electively after failed PTCA. Patients with an ischemic interval up to 70 min. had considerably lower CK and CK-MB values compared to patients with longer ischemic intervals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7875996 TI - [The value of myocardia protection in chronic hypoxic immature rat hearts]. AB - This study examines the efficacy of three methods for myocardial protection during 8 hours of global ischema at 10 degrees C in immature (28 days) rat hearts subjected to lifelong hypoxia afforded by exposure to simulated high altitude. Hearts in group 1 were protected by rapid topical cooling alone, in group 2 by slow pre-arrest cooling with Krebs-Henseleit solution plus topical cooling and in group 3 by coronary perfusion with St. Thomas' Hospital cardioplegia No 2 (STS 2) plus topical cooling. Hearts in groups 4-6 served as controls without hypoxia and were protected accordingly. Parameters of myocardial function (left ventricular pressure, LVP), the metabolic status (myocardial concentration of ATP and creatine phosphate) and endothelial function (response to the vasodilator acetylcholine) were measured. Myocardial protection by rapid topical cooling alone resulted in equal--or significantly improved--postischemic recovery of LVP and endothelial function compared with slow pre-arrest cooling or additional protection with STS 2. The data advocate topical cooling for myocardial protection during surgical correction of cyanotic congenital cardiac disease in early infancy. In this age group, coronary perfusion with cold crystalloid solutions appears to aggravate ischemic endothelial injury. PMID- 7875997 TI - [Type B aortic dissections: surgical technique and results]. AB - Between 1978 and 1992, 70 patients were operated for type B aortic dissection (tear in the descending aorta without involvement of the ascending aorta). 15/70 (21%) patients had an acute dissection (onset of symptoms < 24 h), 19/70 (27%) a subacute dissection (onset of symptoms < 14 days), and 36/70 (51) a chronic dissection (onset of symptoms > 14 days). The indications for surgery in cases of acute dissection were: hematothorax, oliguria, leg ischemia and persistent pain. Persistent hypertension was an additional indication in cases of subacute dissection. In large majority (93%) of chronic dissections the indication for surgery was enlarged aortic diameter. In 86% (60/70) graft replacement of the aorta was performed, in 6% (4/70) extra-anatomic bypass, in 3% (2/70) fenestration, in 3% (2/70) thrombendarterectomy, in 3% (2/70). The overall mortality was 17% (12/70); 27% of acute dissection, 26% for subacute dissection, and 8% for chronic dissection. The morbidity for acute dissection was 73%, of subacute dissection 43%, and of chronic dissection 12%. The most frequent complications were: leg ischemia (8 patients), renal failure (4 patients), paraparesis (4 patients) and sepsis (2 patients). No paraparesis was encountered in surgery of the chronic dissection. Conservative treatment was tried in all acute B-dissections, with surgical therapy being reserved for complications of the dissection, such as rupture, such as rupture, risk of rupture (hematothorax, large aortic diameter resp. expansion, persistent hypertension, persistent pain) or ischemia of distal vascular beds. Long-term survival for chronic type B dissections is good. Strong control of risk factors (hypertension) is essential. PMID- 7875998 TI - [Hemodynamic properties of the hemopump]. AB - The hemopump HP 31 is an improved version of a catheter-mounted, transvalvular, left ventricular assist device, which can be placed into the left ventricle through the ascending aorta. The purpose of this study was to examine the influence of hematocrit and afterload on the pump flow. The hemopump was tested using a flow bench model filled with heparinized bovine blood. The measurements were performed at four various hematocrit values: 16%, 24%, 32%, and 40%. The pump flow was measured at each hematocrit value under increasing afterload pressures (40-120 mm Hg), by all pump speed levels (n = 7). The average pump flow at highest pump speed and lowest afterload was 5.1 +/- 0.3 l/min (mean +/- standard deviation). The influence of afterload on the pump flow was statistically significant (p < 0.001). The highest afterload pressure of 120 mm Hg caused a reduction in pump flow of 24 +/- 5%. The alterations of hematocrit values caused no statistically significant influence on the pump flow (p = 0.72). The results of our study enabled the construction of the nomogram for the in vivo determination of the pump flow. The in vivo performances of the hemopump can be improved through the afterload reduction, especially in the weaning phase of treatment. The oxygen delivery can be improved through the increase in hematocrit values without significant impairment of the pump flow. PMID- 7875999 TI - [Can hyperlipidemia after heart transplantation be optimally and safely treated?]. AB - "Is there any safe and optimal treatment of hyperlipidemia following heart transplantation?" The problem of hypercholesterolemia following heart transplantation if often underestimated. Up to now there is no concept of therapy allowing an optimal adjustment of lipid parameters. Therapeutical trials using ion exchange resins, derivatives of nicotinic acids and fibrates were not successful due to cyclosporine A interaction, hepatotoxicity and limited efficacy of the applied substances. In a prospective, randomized and controlled trial we investigated the effects of the HMG-CoA-reductase inhibitor simvastatin in heart transplant recipients. The study included 70 patients (simvastatin n = 37, control group n = 33). 8 patients died within the first three months following heart transplantation. Purpose of the study was the adjustment of the LDL cholesterol values in the simvastatin treated group to < or = 110 mg/dl. Following 24 months of treatment a mean LDL-cholesterol plasma level of 110 mg/dl was obtained. The corresponding mean value of the control group was 150 mg/dl. The difference between both groups was significant (p < 0.001). In the same period the mean HDL-cholesterol values increased by approx. 15% in both groups (no significant difference [p > 0.05]). The ratio of LDL/HDL-cholesterol was significant lower in the simvastatin treated group (2.28) than in the control group (2.94) (p < 0.05). There was no significant difference in Lp(a) values. No adverse side effects were observed within the observation period of 24 months, particularly no increase in the frequency of rejection episodes. Summarizing the above, we recommend low-dose simvastatin therapy as a safe and optimal treatment of hypercholesterolemia following heart transplantation. PMID- 7876000 TI - [Complex distal radius fracture: value of spongiosa-plasty in combination with external fixator treatment]. AB - 22 Patients with complex fracture of the distal radius (Fernandez III/Frykman VII VIII/AO 23.C) underwent treatment with external fixation and auxiliary autologous bone grafting in purpose to reconstruct and stabilize the radiocarpal articular surface, reset the radius length, obtain a quicker bone healing and avoid secondary radius shortening after removing of the external fixation. In spite of reassessment of radius length in 80% and reconstruction of the radiocarpal articular surface in 75%, late control showed the development of radiological signs of radiocarpal arthritis. 50% of the patients have a moderate loss of strength and motility in the wrist; this seems to be a good result for a very negative selection of complex fractures of distal radius. We recommend autologous bone grafting in treatment of complex fractures of the distal radius with external fixation. PMID- 7876001 TI - [Osseous extensor tendon rupture of the finger joint: surgical technique and results]. AB - Mostly mallet finger can be treated conservatively. In cases of fracture of the distal phalanx open reduction and fixation is recommended. We favour the well established cerclage, yet perform it in a more comfortable way with the use of cannulated drilling. This technique was applied on 13 patients even with lesions several weeks old. The evaluation 5-16 months postoperatively based on radiological, clinical and subjective criteria. We present the technique and the results followed by the discussion of the advantages over conservative and other operative managements. PMID- 7876002 TI - [Arthroscopic intra-articular drainage as the therapy of choice in meniscus ganglia of the knee joint]. AB - The meniscusganglion of the knee is rare but it's an indication for the operation, because it is painful and in the most cases it is connected with an injury of the meniscus. Between 1987 and 1992, 23 patients with meniscusganglion were operated only with the method of the inner drainage. There was no recurrence. We have seen that the concept of the arthroscopy of the knee with the inner drainage of the meniscusganglion is an easy and effective treatment with all the advantages of the arthroscopy. PMID- 7876003 TI - [Clinical aspects and diagnosis of arterial embolism of the upper extremity]. AB - The upper limb embolus is rarely encountered (upper limb:lower limb emboli 1:4 5). Our problem was to determine in which way the paraclinical investigations influence the operation indication. In 1992, we have seen 10 consecutive patients with an upper limb embolus. The characteristics of our patient group are the advanced age and the cardiovascular morbidity. It was always possible to diagnose the emboli clinically. 7 duplex, 6 Dopplers and 2 angiographies were performed and have confirmed the clinical diagnosis and the clinically suspected localisation of the emboli. All the patients were operated in local anesthesy. An embolectomy with Fogarty catheter was done. After the operation, all our patients were asymptomatic. No amputation was done. We do think that when the clinic is clear enough to diagnose an embolus, no other investigations are necessary to the operation indication. PMID- 7876004 TI - [Differential surgical therapy of popliteal entrapment syndrome 1967 to 1992]. AB - From 1967 to 1992 at the University Hospital of Zurich 16 patients (14 male, 2 female) with 22 popliteal artery entrapment syndromes underwent a surgical treatment. In this period several different operation procedures were used. The modern operative procedure depends on the degree of the arteries wall compression. The procedure of choice for minimal compression of arterial wall is a musculo-tendinous decompression with a medial replacement of the popliteal artery. In the cases of severe compression we used autologous venous bypass from femoropopliteal I to popliteal III. PMID- 7876005 TI - [Adventitia resection in cystic degeneration of the popliteal artery]. AB - Adventitial cystic disease is a rare form of non-atherosclerotic stenosis of the popliteal artery. It is caused by synovial-like cysts in the subadventitial tissue layer of the arterial wall causing compression of the lumen. The cysts contain mucinous material similar to that found in joint-ganglia. Popliteal artery stenoses causing claudication in young patients is the leading symptom of this disease. The classical therapy is the surgical excision of the diseased artery and interposition grafting with saphenous vein. As an alternative method we present the technique of complete circumferential resection of the diseased adventitia to decompress the lumen of the artery by removing the cysts completely. This technique is called exarterectomy and has been applied in 2 patients. In both cases we could remove the cysts completely without opening the arterial lumen. Intraoperative arteriography documented complete decompression of the arterial lumen. Both patients presented with excellent results 6 months postoperatively without any symptoms or signs of recurrence. Late results of exarterectomy ar not yet available. PMID- 7876006 TI - [Acute Leriche syndrome in a previously healthy woman: differential diagnosis of embolic occlusion]. AB - The case report describes an acute total ischemia of both legs in a young otherwise healthy woman. Based on the patient's history, the physical findings and further investigations, the differential diagnosis is discussed. The emergency procedure with a successful desobliteration of a strictly localized arteriosclerotic plaque by Fogarty catheter was followed by open thrombendarterectomy 10 days later because of a persistent stenosis. Finally the clinical manifestations of such rare occlusive disease of the aorta are discussed as well as the bilateral ischemic syndrome of the lower extremities originally described by Leriche in 1940. PMID- 7876008 TI - ["Standing waves": differential diagnosis of fibromuscular dysplasia]. AB - We report two recent observations of an angiographic artefact called "standing waves". It results in the same characteristic beaded pictures than fibromuscular dysplasia. It is induced by the angiography catheter and is related to the speed of injection. The possible occurrence of this artefact should be borne in mind whenever the films show dysplastic lesions in more than one artery. PMID- 7876007 TI - [Graft patency and saving the extremity as a function of asymptomatic/symptomatic aneurysm of the popliteal artery and the graft material used]. AB - A 27-year experience with 252 popliteal artery aneurysms in 167 patients is reviewed. Long-term results with respect to graft patency and limb salvage rates are analyzed. The results emphasize the importance of early surgical intervention and demonstrate the superiority of autologous saphenous vein over other graft materials. PMID- 7876009 TI - [Do resorbable suture materials permit safe vascular anastomoses?]. AB - Vascular surgery in growing organisms is still problematic. Especially in surgical therapy of coarctation of the aorta, high restenose rates are documented if non-absorbable polypropylene and running suture technique ist used. Theoretically, absorbable suture material allows a running suture technique with less restenose rates. Our study compares absorbable (polyglyconat and polydioxanon) with non-absorbable (polypropylene) suture material for repair of aorta in growing dogs. Anastomoses performed with absorbable suture material show after one year very good functional results without any local complications. In conclusion we can say that absorbable suture material allows formation of safety vascular anastomoses and doesn't impair growth of anastomoses. PMID- 7876010 TI - [Symptomatic enterothorax in right-sided dorsal rupture of the diaphragm]. AB - Traumatic avulsion of the right diaphragm from the lumbocostal arch is a very rare lesion. The authours report the case of a 27-year-old man who had suffered a severe polytrauma with blunt thoracic injury, fracture of the lumbar spine, Malgaigne-type fracture of the pelvis and fracture of the femoral shaft on the right side, 10 years before. At the time of injury the lesion of the diaphragm went unnoticed. The diagnosis was made 10 years later when the patient was referred for chronic right thoracic pain combined with postprandial abdominal distension and crampy pain in the abdomen. The chest radiogram and CT-scan showed displacement of the right kidney and most of the right colon into the thorax due to avulsion of the diaphragm from its dorsal insertion on the lumbocostal arch. Surgical repair was necessary to obtain relief from pain and to prevent intestinal obstruction. Reduction of the hernia, reinsertion of the diaphragm to the lumbocostal arch and reinforcement of the repair with a prolene mesh prosthesis was performed through a right thoracophrenolumbotomy incision. PMID- 7876011 TI - [Preventive digitalis therapy in open thoracotomy]. AB - Prophylactic digitalization is still recommended after open lung surgery in order to prevent cardiac arrhythmias in the postoperative period. Since a beneficial effect of this potentially harmful medication is only poorly documented, we conducted a prospective randomized trial. Patients undergoing elective open lung surgery were divided into two groups one of which received digoxin postoperatively, the other not. Randomization was performed independently in three groups with regard to the extent of surgery, i.e. pneumonectomies in patients of any age, (bi-)lobectomies in patients > 50 and other (less extended) operations in patients > 60. Patients who were either too young for either group or who had already taken digoxin before surgery were followed separately. Monitoring was performed continuously in the ICU and conventional ECG was registered after 24, 48 and 72 hours and weekly until dismission.--Cardiac arrhythmias are very frequent in the early postoperative period with a maximum between the third and the fifth postoperative day. Any kind of arrhythmias were present in 19 of 30 patients (63%) compared to 14 of 35 patients (40%) in the control group. Symptomatic arrhythmias that needed treatment occurred in 11.4% of the control group, but in 33.3% of the patients with prophylactic digitalization. We therefore conclude that a general prophylactic digitalization after open lung surgery is not indicated, but that arrhythmias should be treated individually. PMID- 7876012 TI - [Sacral chordoma: a consideration in low back pain]. AB - We present the case of a sacral chordoma (S3-S5). Its diagnostic problems as well as its pathological properties and the epidemiologic situation are discussed. The therapy and the surgical procedure are outlined. PMID- 7876013 TI - [Diarrhea and peritonitis in infection caused by type A beta hemolytic streptococcus]. AB - During the last years the cases of severe group A streptococcus infection have increased. The clinical manifestation of this streptococcal toxic shock syndrome is similar to the better known toxic shock syndrome (TSS) provocated by staphylococcus. Shock, bacteremia and acute respiratory distress syndrome are common features, and death has been associated with this infection in 30% of patients. We present the case of a 46-year-old man who fell gravely ill with sepsis, diarrhoe, scarlatina rash, desquamation of hands and feet and acute abdomen caused by group A streptococcus infection. Finally we discussed the possible port of entry of this infection, the different clinical manifestation and the concepts of treatment. PMID- 7876014 TI - [Intestinal drug transport: a surgical problem?]. AB - The case of a 35-year-old man is reported, who presented himself in the emergency room with anxiety and hallucinations. He then passed a small oval pack consisting of a dark paste wrapped in cellophane with his stool. This led to the suspicion of a "body packer syndrome" with cocaine intoxication. The plain abdominal X-ray revealed multiple oval structure scattered over the entire gastrointestinal tract. Cocaine metabolites in the urine confirmed the diagnosis. During the following whole-bowel irrigation the patient had a grand mal seizure. In order to accelerate the retrieval of this threatening load, surgical evacuation was immediately executed. 78 packs containing 650 grams cocaine were removed through a gastrotomy and a coecotomy, respectively. Two of these packs were leaking. Following an uneventful postoperative course the patient was discharged from the hospital 11 days later. According to the literature the recommended treatment for cocaine body packers is whole bowel irrigation. Operative treatment is mandatory in cases of small bowel obstruction or drug intoxication due to leaking packs. PMID- 7876015 TI - [Quality assurance in surgery]. AB - Since 1990 the Surgical Department of the Kantonsspital Schaffhausen has been taking part in a quality assurance program organized by the "Bundesland Baden Wurttemberg". The traceroperation "appendectomy" will be used to demonstrate the principle of quality assurance and our results for the years 1991 and 1992 will be presented. PMID- 7876016 TI - [Perityphlitic abscess after perforated appendicitis with carcinoid of the appendix]. AB - Appendix carcinoid in children is a rare condition which is found by accident at the histological examination of the appendix. We report on a rare case in which a covered perforation of a diverticulum had occurred. First of all the patient was treated conservatively with antibiotics and 2 months later the appendectomy a froid was performed. The annual follow-up of these patients is certainly indicated. PMID- 7876017 TI - [Volvulus of the small intestine as a cause of primary acute abdomen]. AB - As a cause of small intestine occlusion, volvulus is often a consequence of a band or adhesions. Except in infants, it is rarely the primary cause of symptomatology. Between January 1976 and December 1992, 13 patients (7 women and 6 men, mean age of 56.8 years) were admitted in our department for an acute abdomen due to a spontaneous primary volvulus of the small bowel. Clinical examination and laboratory tests did not help in preoperative diagnosis. All patients underwent an explorative laparotomy. Six patients had had prior abdominal surgery but none of them presented adhesion or band. In 8 patients (62%), detorsion was sufficient. Resection of a segment of small bowel was necessary in 4 patients. Gangrenous of the entire bowel was observed in one patient who rapidly died. Two patients presented minor complications. One patient with Down syndrome died of bronchoaspiration. One patient has been reoperated on one year later for recurrence of the volvulus, and underwent a Noble procedure. We conclude that volvulus of the small bowel is a rare cause of acute abdomen that must be remembered. Early surgery is mandatory to reduce the risk of gangrene, which is known to double the mortality. Laparoscopy will be helpful in early diagnosis and therapy. PMID- 7876018 TI - [Pneumatosis intestinalis: a rare and difficult problem]. AB - We present a case of a 74-year-old-woman who developed 3 episodes of intestinal pneumatosis, 2 times complicated by pneumoperitoneum, with consequent lethal outcome after 4 months. Intestinal pneumatosis, according to the literature, is a difficult and rare problem, associated with a large number of current diseases, can be complicated by pneumoperitoneum, mostly without clear etiology, whose treatment remains empirical (antibiotics, O2-therapy), not excluded laparotomy, if the clinical situation requires it. PMID- 7876019 TI - [Mesenteric infarct in acute mesenteric vein thrombosis]. AB - Mesenteric venous thrombosis is an infrequent but distinct form of intestinal ischemia. We report 2 cases of acute mesenteric venous thrombosis, treated successfully by carrying out intestinal resection and postoperative anti coagulation (Heparin, Sintrom). Both patients were diagnosed in the operating room. Improvements in computed tomography may identify patients earlier in their clinical course, heparin has both a primary therapeutic role in early disease and a postoperative adjunctive role in advanced disease. With such care, these patients can expect an acceptable prognosis. PMID- 7876020 TI - [Panniculitis mesenterialis, a rare disease]. AB - Panniculitis mesenterialis is an illness of the mesenterium of the small intestine and is not familiar to all clinical physicians. The rare reports in the literature mostly describe a good outcome with a few cases ending lethal. Pathologists paying attention to detect panniculitis during postmortem examination report about an incidence of about 1%. This discrepancy may be based on the fact that only extended changes of the mesenterial fat tissue cause symptoms. The pathological base consists in extensive necrosis of fat tissue with fibrosis of the mesenterium. Aetiology is unknown, diagnosis is usually made during laparotomy. There is no specific treatment, prognosis is generally good. PMID- 7876021 TI - [Laparoscopic cholecystectomy: heat damage to the liver caused by hooked electrode and laser]. AB - To control heat damage in the liver after cholecystectomy caused by electrosurgery or Laser, gallbladders were resected at autopsy partly by the Holmium:YAG-Laser and Nd:YAG-Laser and partly by electrosurgery. Heat damage was documented by histological examinations of the liver-bed of the gallbladder. Microscopical evaluation showed that electrocautery tends to produce deeper heat damage in the liver-tissue than the Holmium:YAG-Laser. PMID- 7876022 TI - [Laparoscopically assisted formation of end stage and loop ileostomies and colostomies]. AB - Especially in obese or severely ill patients, forming of an ileostomy or colostomy can be very difficult and laparotomy itself can lead to many complications. The intraabdominal part of this operations can easily be performed laparoscopically. The method is quick and simple and many complications can be avoided. PMID- 7876023 TI - [Continuous distance suture of the colon--an alternative to the stapler]. PMID- 7876024 TI - [Therapeutic approach to para-esophageal hernia]. AB - The charts of all the patients operated upon for paraesophageal hernia (HPO) were reviewed. 24 patients could be found between 1976 and 1992. The mean age was 64 years, with 15 men and 9 women. 15 patients had a pure HPO, whereas 9 had a mixed hernia (HPO and laxial hiatal hernia). 3 patients presented with acute symptoms, and 2 of them were operated on emergently. The remaining patients had elective surgery, consisting of reduction of the stomach (all cases), excision of the hernia sac (12), closure of the diaphragm (17) and gastropexy (8). There was no mortality. Due to the fact that acute complications occur in as much as 30-40% of the cases, elective surgery should be proposed to any patient with a known paraesophageal hernia if the operative risks are not prohibitive. A careful preoperative assessment including endoscopy and pH-manometry of the esophagus will provide arguments to add a antireflux procedure to the standard operation, which should include reduction of the stomach, resection of the sac, closure of the hiatal defect and gastropexy. PMID- 7876025 TI - [Herniation of the cecum and ascending colon through the Winslowi foramen in the bursa omentalis]. AB - Herniation through the foramen of Winslow (HFW) is exceedingly rare, the ileum, coecum or ascending colon is involved mostly. One new case is presented here to illustrate the clinical findings, which are often discreet, and the characteristical radiographic features, which can lead to definitive preoperative diagnosis. Treatment is by surgical reduction of the hernia, resection of non viable bowel or fixation of coecum and ascending colon. Closure of the foramen is generally considered unnecessary. Without delay in diagnosis and treatment, the former high letality rate of the condition is now nearly zero. PMID- 7876027 TI - [Signet ring cell carcinoma of Vater's papilla: a very rare malignancy]. AB - We describe a rare variant of carcinoma of the ampulla of Vater. A 70-year-old man with several illnesses and a newly appeared jaundice was investigated and a signet-ring cell carcinoma of the ampulla of Vater diagnosed. We performed a local transduodenal excision. One year after operation the patient is asymptomatic. This is the second case report in the literature. PMID- 7876026 TI - [Lichtenstein alloplastic repair of inguinal hernia]. AB - Tension-free repair, a prerequisite for long-term stability, cannot always be achieved with conventional techniques established for groin reconstruction. Lichtenstein gathered substantial experience simply by closing the hernia in a tension-free fashion using prosthetic material. However, most surgeons fearing graft infection are reluctant to further evaluate this technique. In a feasibility study we entered 70 patients (29 patients with recurrent hernia) receiving a polypropylene mesh (Marlex) to bridge the defect from the inguinal ligament to the internal oblique muscle. Only 1 wound infection and 1 local hematoma requiring reoperation were observed. Nearly 2 years follow-up data revealed no case of recurrence. The Lichtenstein procedure deserves more attention from surgical community and might be a reliable technique esp. in large hernias and redos. PMID- 7876028 TI - [Surgical therapeutic possibilities in pediatric shaft fractures using intramedullary nailing]. AB - We can report our experience of this operative method by internal rush pin fixation of shaft fractures in childhood. Our results are very convincing and we can say that this method is successful and a good alternative in future by the possibility of a functional treatment. PMID- 7876029 TI - [Technique of laparoscopic descendo-rectostomy for reconstruction of intestinal continuity after Hartmann operation]. AB - Reestablishing bowel continuity subsequent to sigma resection with terminal descendostomy and blind closure of the rectum (Hartmann procedure) by a descendo rectostomy (DR) is well suited for a laparoscopic approach. One part of the operation is performed extracorporally, and with the laparoscopic operation there is no need to consider radical tumor surgery or staging rules. We demonstrate our techniques for laparoscopic DR. - Operational steps. - A. conventionally: complete dissection of the descendo-stoma, insertion of a 29 or 31 mm circular stapler head secured by a purse string suture and repositioning of the colon into the abdomen; blunt dissection of reachable intra-abdominal adhesions with a finger, and placement of a 10-mm umbilical trocar using palpation; air tight closure of the abdominal wall at the original stoma site. B. laparoscopically: upon creation of a CO2 pneumoperitoneum, placement of two additional 10 mm trocars; adhesiolysis of the pelvis; preparation of the blind rectal stump; transanal insertion of the circular stapler and perforation of the rectal stump; bringing down the proximal colon into the pelvis (possible need to mobilise the splenic flexure); reconnecting the stapler head with the instrument and firing the stapled anastomosis. - The postoperative period was uneventful. Using a laparascopic approach for a DR following Hartmann's procedure is an attractive and viable method to reestablish bowel continuity. PMID- 7876030 TI - Evaluation of the relative sensitivity of chromosome painting (FISH) as an indicator of radiation-induced damage in human lymphocytes. AB - Fluorescence in situ hybridization with whole chromosome libraries, also known as chromosome "painting", is an easy and rapid method for detection of chromosome aberrations. To evaluate the sensitivity of this in radiation dosimetry we have made comparisons with G-banding analysis and also with physicochemical measurements of radiation induced DNA damage (DNA strand breaks and 8 hydroxydeoxyguanosine formation). Heparinised human blood was irradiated at room temperature with a range (0-10 Gy) of gamma irradiation from a cobalt 60 source. Chromosome spreads prepared from phytohaemagglutinin stimulated "whole blood" lymphocyte cultures were hybridized in situ with the whole chromosome 1 library, coded, and scored for aberrant cells. Dose response curves plotted as percent abnormal cells obtained by the two cytogenetic methods were similar and it would appear that chromosome "painting" compared favourably with G-banding for the detection of aberrations. The measurement of DNA strand breaks by a fluorimetric alkaline unwinding assay showed similar sensitivity to chromosome "painting" whereas the formation of 8-hydroxydeoxyguanosine did not correlate with aberration frequencies. PMID- 7876032 TI - Synaptonemal complex analysis of hybrid and purebred water buffaloes (Bubalus bubalis). AB - The morphology of the synaptonemal complex (SC) in river (2n = 50) and swamp (2n = 48) water buffaloes and their hybrids, was studied by electron microscopic analysis. In 2n = 49 hybrids, F2 and backcrosses the formation and pairing behaviour of a trivalent at zygotene-pachytene confirmed that river and swamp buffaloes differ by a centromere-to-telomere (C-T) tandem fusion. While 29% of spermatocytes from a purebred river buffalo and 16% from a purebred swamp buffalo had pairing abnormalities, a significantly higher frequency of abnormalities (48 72%) was recorded in F1, F2, and backcrosses with 2n = 48, 49 or 50. Highest abnormality frequencies occurred in 2n = 49 bulls. Abnormal pairing configurations often resulted from interactions between unpaired chromosome axes or segments. Zygotene-pachytene meiotic progress appeared delayed in hybrid bulls, and the frequency of SC abnormalities decreased from XY type I substage to type V substage. The variation in SC abnormality data from hybrids was consistent with the levels of sperm abnormality previously reported. PMID- 7876031 TI - Genetic variation in the hooded seal, Cystophora cristata, based on enzyme polymorphism and multi-locus DNA fingerprinting. AB - The genetic population structure of hooded seal, Cystophora cristata, was examined by electrophoretic analysis of allozymes and with multilocus DNA fingerprinting. Samples were collected in the Jan Mayen area and off Newfoundland. Allele products were resolved by isoelectric focusing. Only five of 32 protein-coding loci investigated were polymorphic at the 95% level. The proportion of polymorphic loci was estimated to P = 0.233, and average heterozygosity to H = 0.047. Tissue distribution, genotype distribution, and approximate pI (4 degrees C) of the proteins are reported. The allele frequencies of the AAT-2, GPD-2, and GPI-1 loci, were used in genetic comparisons of samples from the two stocks. Chi-square and G-tests showed no significant difference among the samples from the two groups. Highly variable profiles of HaeIII, HinfI and MboI digested genomic DNA were revealed using the human minisatellites 33.15 and 33.6 (HinfI digests only) as hybridization probes. Comparisons of band sharing coefficients from HinfI and MboI digest were carried out. We were unable to detect significant differences in band-sharing between Newfoundland and the Jan Mayen area. The hypothesis that there is a considerable degree of intermixing between the stocks cannot be rejected. PMID- 7876033 TI - Assignment of GRP78 gene to swine chromosome 1q2.12-->q2.13 by fluorescent in situ hybridization. PMID- 7876034 TI - Sensory gating deviance in schizophrenia in the context of task related effects. AB - To replicate the findings of a sensory gating deficit in schizophrenia, and to determine if normals and schizophrenics are equally affected by cognitively mediated task-relevant factors, 10 healthy and 10 schizophrenic young adults were tested in two experimental conditions. In the first condition a pair of identical auditory clicks (conditioning stimulus and testing stimulus) was administered at an inter-stimulus interval fixed at 500 msec. In the second condition, the second stimulus could have one of two possible frequencies, and subjects were required to count the presentations of one and ignore the other. Subjects also completed two matched blocks of single stimulus (i.e. testing only) presentations to provide a baseline for assessing the effect of the warning stimulus on the evoked response. We found, in disagreement with previous results, that in schizophrenics, passive exposure to the paired stimuli produced a suppression of P50 amplitude to the second stimulus, that did not differ from that found in normals. However, under paired presentation conditions, testing P50 amplitude in normals, but not in schizophrenics, was enhanced by the count/no-count task introduction. We suggest that both groups are equally susceptible to the task independent (possibly "hard-wired") suppressing effect of a conditioning stimulus presentation. However, only normals seem to exhibit a task-dependent effect, whose action at the P50 range demands the presence of a warning (conditioning) stimulus. Inspection of the full epoch data showed an apparently lesser task related, warning dependent modulation of early ERP activity in schizophrenics, and a normal (or even supernormal) modulation of late activity. We consider this to support a notion of an early processing deficit in schizophrenia. PMID- 7876035 TI - Electrodermal differentiation of deception: the effect of choice versus no choice of deceptive items. AB - In the differentiation-of-deception paradigm (DDP), the experimental and control conditions, respectively, consist of questions answered deceptively (D) and honestly (H). Previous DDP studies with the electrodermal SCR as the dependent variable have yielded the basic increase in responding to D relative to H questions (D > H), and have indicated that this effect is probably not due to cognitive factors such as differential retrieval difficulty, and is also relatively unaffected by motivational factors. To test the notion that the D > H effect does not represent genuine deception because of the elimination of the element of choice in the DDP, the present study varied, between two groups of 16 subjects, the degree to which subjects could choose which questions they would answer deceptively. If choice were necessary, or even important, for the differentiation-of-deception phenomenon, the D > H effect should have been greater in the free-choice condition, but the (nonsignificant) trend was in a direction opposite to this prediction. Another orthogonally-varied, between subject manipulation, was the relative frequency of D and H items. The basic electrodermal D > H phenomenon, including the curious lack of response habituation during the session, has now been duplicated over a variety of conditions, but the mechanisms underlying the phenomenon are far from being well understood. PMID- 7876036 TI - Effects of vocalization on cardiovascular and electrodermal responses during mental arithmetic. AB - This study assessed the contribution of vocalization to autonomic responses during mental arithmetic. Specifically this study compared the autonomic responses of subjects during aloud and silent phases of repeated mental arithmetic tasks. The results were consistent for both tasks. As expected, heart rate and skin conductance responses were elevated during the aloud phases. Preejection period and cardiac output reactions, however, were greater during the silent phases. Furthermore, stroke volume declined during the aloud phases, but was maintained near resting levels during the silent phases. There were no phase effects for systolic pressure, diastolic pressure, or total peripheral resistance. The pattern of autonomic responses between aloud and silent phases of mental arithmetic suggest that the relationship between vocalization and autonomic response is not unidirectional but varies depending on the physiological parameter under investigation. PMID- 7876037 TI - Event-related theta rhythms in cat hippocampus and prefrontal cortex during an omitted stimulus paradigm. AB - In a recent study on human subjects which performed a time prediction task in an omitted stimulus paradigm we found an increase in the amplitudes of evoked potentials (EPs) for the stimulus preceding the omitted stimuli, probably due to expectancy and focused attention. The amplitude increases were dominant over frontal and parietal association areas and were mainly reflected in enhancements of the theta (3-6 Hz) components. In the present study we analyse the responses of the auditory cortex (GEA, gyrus ectosylvianus anterior), different parts of hippocampus (CA1, CA3), reticular formation (RF), and motor cortex (MC) of the cat brain using a similar paradigm. Similar theta component increases of the EPs were obtained in various parts of the hippocampus, which were dominant in pyramidal cell layers (CA3, CA4), and in motor cortex. The results are interpreted as signs of a diffuse theta response system in the brain including mainly the hippocampus and frontal and parietal association areas. The diffuse theta system is probably involved in general attention and expectancy processes. PMID- 7876038 TI - Low resolution electromagnetic tomography: a new method for localizing electrical activity in the brain. AB - This paper presents a new method for localizing the electric activity in the brain based on multichannel surface EEG recordings. In contrast to the models presented up to now the new method does not assume a limited number of dipolar point sources nor a distribution on a given known surface, but directly computes a current distribution throughout the full brain volume. In order to find a unique solution for the 3-dimensional distribution among the infinite set of different possible solutions, the method assumes that neighboring neurons are simultaneously and synchronously activated. The basic assumption rests on evidence from single cell recordings in the brain that demonstrates strong synchronization of adjacent neurons. In view of this physiological consideration the computational task is to select the smoothest of all possible 3-dimensional current distributions, a task that is a common procedure in generalized signal processing. The result is a true 3-dimensional tomography with the characteristic that localization is preserved with a certain amount of dispersion, i.e., it has a relatively low spatial resolution. The new method, which we call Low Resolution Electromagnetic Tomography (LORETA) is illustrated with two different sets of evoked potential data, the first showing the tomography of the P100 component to checkerboard stimulation of the left, right, upper and lower hemiretina, and the second showing the results for the auditory N100 component and the two cognitive components CNV and P300. A direct comparison of the tomography results with those obtained from fitting one and two dipoles illustrates that the new method provides physiologically meaningful results while dipolar solutions fail in many situations. In the case of the cognitive components, the method offers new hypotheses on the location of higher cognitive functions in the brain. PMID- 7876039 TI - Dimensional analysis of human EEG during experimental affective experience. AB - The present investigation was designed to study whether dimensional complexity of EEG discriminates between internal and external attentional demands during affective experience. In the first task Ss were waiting for a slight electric shock (affective intake condition). In the second task Ss were engaged in the controlled imagery involving the emotional experience 'programmed' during intake task (affective rejection condition). Both affective tasks were compared to the controlled rest condition. The results of imagery trial replicated previous demonstration of the increased dimension of EEG during imagery in comparison to perceptual processing, with differences, confined to frontal and partly to central sites. Affective intake trial in comparison to rest condition was characterized by significantly higher dimensional estimates over the central and more posterior (parietal and occipital) areas. PMID- 7876040 TI - Synchronous changes of psychophysiological responses and tone pressure: effect of musical training. AB - This study was designed to examine the relationship between psychophysiological responses and tone pressure during music. The main findings were as follows: (1) Mean increments of heart rate (HR) and respiration rate (RR) did not correlate with mean increments of tone pressure. (2) Musical individuals showed consistent changes between HR and tone pressure. (3) Non-musical person showed a high correlation between changes of HR and tone pressure in only a rhythmic and dynamic musical piece. These results showed that trained musicians respond differently from individuals having no musical training. PMID- 7876041 TI - EEG changes during forced alternate nostril breathing. AB - The effects of 10 min forced alternate nostril breathing (FANB) on EEG topography were studied in 18 trained subjects. One type of FANB consisted in left nostril inspiration and right nostril expiration and the other type in right nostril inspiration and left nostril expiration. Mean power in the beta bands and partially in the alpha band increased during FANB irrespective of the type of nostril breathing. In addition, hemisphere asymmetry in the beta 1 band decreased in the second half of FANB suggesting that FANB has a balancing effect on the functional activity of the left and right hemisphere. PMID- 7876042 TI - Microalbuminuria and its clinical significance. PMID- 7876043 TI - Malondialadehyde: a marker of lipid peroxidation. PMID- 7876044 TI - Microalbuminuria in non insulin dependent diabetes and essential hypertension: a marker of severe disease. AB - Sixty five (65) hypertensive, 91 non-insulin dependent diabetes and 50 matched, healthy controls were examined for the presence of microalbuminuria, using the Micral strip test. Microalbuminuria was observed in 25 per cent of diabetics and 21.54 per cent of hypertensive subjects. None of the controls demonstrated microalbuminuria. Diabetics with microalbuminuria were poorly controlled and demonstrated significantly higher systolic pressure. In hypertensive subjects, microalbuminuria was seen more in patients with severe disease. In both diabetics and hypertensives, presence of microalbuminuria was significantly influenced by the disease duration. PMID- 7876045 TI - Malondialdehyde as a sensitive marker of inflammation in patients with rheumatoid arthritis. AB - Malondialdehyde (MDA) levels in the serum were estimated by MDA-TBA (Thiobarbituric Acid) spectro colorimetric assay method in 23 rheumatoid arthritis (RA) patients and were compared with those in 18 healthy subjects. It was found that the mean levels of MDA (265.15 +/- 68.8 n moles/100 ml) in patients with RA were found to be significantly elevated when compared to the mean of that of controls (128.76 +/- 37.8 n moles/100 ml). This study reveals that MDA assessment appears to be a sensitive marker of inflammation in this chronic auto immune disorder and would help in understanding the nature of inflammatory damage at a cellular level. PMID- 7876046 TI - Prognostic factors in Guillain-Barre' syndrome. AB - Prospective prognostic evaluation of various clinical and investigative parameters in 24 patients of Guillain-Barre' syndrome revealed poor prognosis in patients having rapid onset of illness, severe degree of paralysis and muscle wasting, prolonged period of peak paralysis lasting for more than 2 weeks and delayed onset of recovery not commencing within 3 weeks from the onset of weakness. Bulbar paralysis and respiratory involvement adversely affected the outcome. Electrodiagnostic evidence of fibrillation, polyphasic action potentials and markedly reduced amplitude of motor action potentials were indicative of poor prognosis. However, age and sex of the patients, severity of sensory loss, sphincteric disturbances, CSF findings and nerve conduction velocities did not significantly affect the outcome. Autonomic dysfunctions were noticed in 66.6% cases but were mostly mild and transient, and did not affect the long-term results. PMID- 7876047 TI - Effect of intravenous streptokinase on left ventricular function following acute myocardial infarction--an echocardiographic study. AB - 160 patients with first attack of acute myocardial infarction (AMI), admitted within 6 hours after onset of chest pain, were divided into two groups--80 receiving intravenous streptokinase (IVSK, Gr. I) an 80 being treated without IVSK (GR. II). They were studied for pre-discharge (12.5 +/- 2.5 days-post admission) echocardiographic LV function. Gr. I pts received 1.5 million units of IVSK within 6 hrs of onset of chest pain, alongwith beta-blockers, aspirin and heparin unless contraindicated. Gr. II received all these except IVSK alongwith conventional therapy. Highly significant (P < 0.001) improvement was noted in the end-diastolic volume (EDV), end-systolic volume (ESV), Ejection fraction (EF) and regional wall motion score (RWMS) in the anterior wall (AW) AMI group when treated early with IVSK. In the inferior wall (IW) AMI group significant decrease was observed in the EDV and ESV (P < 0.001) and RWMS (P < 0.05), but the difference was not statistically significant for EF. Early high-dose short term IVSK infusion is thus associated with highly significant improvement in LV functions--regional as well as global--especially in AW AMI; in IWAMI the improvement is less marked. PMID- 7876048 TI - Emerging facets of diastolic heart failure. AB - One hundred patients with congestive cardiac failure (52 males and 48 females) with age ranging from 16 to 56 yrs (mean age 42 +/- 6) were studied to determine the relative prevalence of systolic and diastolic failures, their clinical profiles and common aetiologies. Age matched 25 control subjects were also studied to established a normal range of echocardiographic values for LV diastolic function. Thirty eight patients (38%) were found to have pure diastolic heart failure and another 5 (5%) and 57 (57%) were detected to have mixed and systolic failures respectively. An attempt to correlate the clinical assessment of diastolic failure with echo doppler study showed the sensitivity and specificity of the clinical criteria for diagnosis of diastolic heart failure to be 100% and 91.94% respectively. Of the 38 cases of diastolic failure detected 39.5% had hypertension, 31.6% ischaemic heart disease and 13.16% hypertrophic cardiomyopathy. PMID- 7876049 TI - Prevalence of proteinuria in non-insulin dependent diabetes. AB - Proteinuria was estimated in 600 non-insulin dependent diabetes mellitus (NIDDM) patients in 24 hrs collection of urine. The test was repeated at least twice in a year to confirm the persistence of proteinuria. Mild proteinuria (200-500 mg/d) occurred in 94 (15.7%) and nephropathy (> 500 mg/d) in 112 (18.7%) patients. Nephropathy commonly occurred with long-standing diabetes (> 10 years). Development of proteinuria correlated directly with the duration of diabetes, diastolic and systolic blood pressure, age of the patients, serum creatinine and inversely with creatinine clearance. Retinopathy was seen in 75% of those with nephropathy. It is concluded that proteinuria occurs in one third of NIDDM patients and the risk of nephropathy increases with duration of disease. PMID- 7876050 TI - Drug induced endocrine problems. AB - Drug induced effects on the various endocrine and metabolic processes constitute a very common differential diagnostic possibility in investigating endocrine disorders. Knowledge of drug-effect is of paramount importance to avoid unnecessary and expensive investigations and treatment. Since most of the effects are type A effects and hence predictable, reduction of dose or modification of therapy is sufficient to reverse the adverse effects. PMID- 7876051 TI - Strategies for prevention of thalassemia and hemoglobinopathies. PMID- 7876052 TI - Hypersensitive reactions on readministration of streptokinase following acute myocardial infarction. PMID- 7876054 TI - Rheumatic fever--decline and resurgence. PMID- 7876053 TI - Epilepsy: a common manifestation of neurocysticercosis--its diagnosis and management. PMID- 7876055 TI - Pseudotumour and factor X deficiency--a rare presentation. PMID- 7876056 TI - Plasma cell leukemia--report on two cases. PMID- 7876057 TI - Antiphospholipid syndrome--a case report. PMID- 7876058 TI - Successful use of CAPD as ESRD therapy in a HIV positive patient. PMID- 7876059 TI - Change in the ABO blood group phenotype. PMID- 7876060 TI - Wolfram (DIDMOAD) syndrome with diabetic retinopathy. PMID- 7876061 TI - Malignant melanoma presenting as compressive myelopathy. PMID- 7876062 TI - Ankylosing spondylitis with lung involvement mimicking pulmonary tuberculosis and rapidly progressing chronic renal failure. PMID- 7876063 TI - Cervical syringomyelia in a case of brainstem tumour. PMID- 7876064 TI - Zollinger Ellison syndrome. PMID- 7876065 TI - Granuloma pyogenicum. PMID- 7876066 TI - Acquired deficiency of factor XIII. PMID- 7876067 TI - Acute psychosis with Norfloxacin. PMID- 7876068 TI - Incidence of coronary artery disease in asymptomatic uncomplicated essential hypertension patients. PMID- 7876069 TI - Incidence of coronary artery disease in asymptomatic uncomplicated essential hypertension patients. PMID- 7876070 TI - Incidence of coronary artery disease in asymptomatic uncomplicated essential hypertension patients. PMID- 7876071 TI - Incidence of coronary artery disease in asymptomatic uncomplicated essential hypertension patients. PMID- 7876072 TI - Diagnosis of gastroenteritis is a misnomer. PMID- 7876073 TI - Aetiology and management of hepatic venous outflow obstruction. PMID- 7876074 TI - LGB syndrome: is albuminocytological dissociation essential for the diagnosis? PMID- 7876075 TI - Swinholide A is a microfilament disrupting marine toxin that stabilizes actin dimers and severs actin filaments. AB - Swinholide A, isolated from the marien sponge Theonella swinhoei, is a 44-carbon ring dimeric dilactone macrolide with a 2-fold axis of symmetry. Recent studies have elucidated its unusual structure and shown that it has potent cytotoxic activity. We now report that swinholide A disrupts the actin cytoskeleton of cells grown in culture, sequesters actin dimers in vitro in both polymerizing and non-polymerizing buffers with a binding stoichiometry of one swinholide A molecule per actin dimer, and rapidly severs F-actin in vitro with high cooperativity. These unique properties are sufficient to explain the cytotoxicity of swinholide A. They also suggest that swinholide A might be a model for studies of the mechanism of action of F-actin severing proteins and be therapeutically useful in conditions where filamentous actin contributes to pathologically high viscosities. PMID- 7876076 TI - cDNA cloning and characterization of a Cek7 receptor protein-tyrosine kinase ligand that is identical to the ligand (ELF-1) for the Mek-4 and Sek receptor protein-tyrosine kinases. AB - We have isolated a murine cDNA encoding a ligand for the Cek7 receptor protein tyrosine kinase (RPTK), a member of the Eph/Eck RPTK subfamily. Sequence analysis predicts an open reading frame of 209 amino acids with a predicted molecular mass of 24 kDa. The Cek7 ligand shows a 48% sequence identity at the protein level to B61, a ligand for the related Eck RPTK, 30% to the Cek5 ligand, 59% to the recently cloned Ehk1-L, and identity to ELF-1, a recently described ligand for the Mek4 and Sek RPTKs. The expressed Cek7 ligand is functionally active as it induces autophosphorylation of the Cek7 RPTK. PMID- 7876077 TI - Growth hormone stimulates the tyrosine phosphorylation of the insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase in primary adipocytes. AB - Insulin receptor substrate-1 (IRS-1) is tyrosine-phosphorylated in response to insulin resulting in association with and activation of phosphatidylinositol 3 kinase (PI 3-kinase), thereby initiating some of the effects of insulin. We have recently shown that the insulin-like effects of growth hormone (GH) in adipocytes can be inhibited by the selective PI 3-kinase inhibitor wortmannin (Ridderstrale, M., and Tornqvist, H. (1994) Biochem. Biophys. Res. Commun. 203, 306-310), suggesting a similar role for PI 3-kinase in GH action. Here we show that IRS-1 is tyrosine-phosphorylated in a time- and dose-dependent manner in response to GH in primary rat adipocytes. This phosphorylation coincided with the extent of interaction between IRS-1 and the 85-kDa subunit of PI 3-kinase as evidenced by coimmunoprecipitation. Stimulation with 23 nM GH increased the PI 3-kinase activity associated with IRS1 4-fold. Our data suggest that GH-induced tyrosine phosphorylation of IRS-1 and the subsequent docking of PI 3-kinase are important postreceptor events in GH action. The mechanism for the phosphorylation of IRS-1 induced by GH is unknown, but involvement of JAK2, the only known GH receptor associated tyrosine kinase, seems possible. PMID- 7876078 TI - Oxidized low density lipoprotein suppresses activation of NF kappa B in macrophages via a pertussis toxin-sensitive signaling mechanism. AB - The interaction of oxidized low density lipoprotein (ox-LDL) and macrophages is generally believed to be a significant inductive step in atherogenesis. Endocytosis of ox-LDL by scavenger receptors (SR) on macrophages is one result of this interaction, as is suppressed expression of several lipopolysaccharide (LPS) stimulated, inflammatory genes such as tumor necrosis factor-alpha (TNF-alpha). Events subsequent to SR ligation, including intracellular signaling events if any, have not been established. We report here that ox-LDL initiates rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate 2 (PIP2) and intracellular fluxes of Ca2+ in macrophages, both of which are sensitive to pertussis toxin. ox LDL also suppresses the LPS-induced binding of macrophage extracts to an NF kappa B sequence oligonucleotide and the LPS-initiated accumulation of RNA specific for TNF-alpha. These latter two effects are pertussis toxin-sensitive. Ligation of SR by ox-LDL thus initiates a pertussis toxin-sensitive signaling pathway in macrophages, which involves hydrolysis of PIP2 and which can suppress expression of the TNF-alpha gene by modulating activation of NF kappa B. PMID- 7876079 TI - 1-Chloro-2,4-dinitrobenzene is an irreversible inhibitor of human thioredoxin reductase. Loss of thioredoxin disulfide reductase activity is accompanied by a large increase in NADPH oxidase activity. AB - Human thioredoxin reductase is a dimeric enzyme that catalyzes reduction of the disulfide in oxidized thioredoxin by a mechanism involving transfer of electrons from NADPH via FAD to a redox-active disulfide. 1-Chloro-2,4-dinitrobenzene (DNCB) is an alkylating agent used for depleting intracellular GSH and also showing distinct immunomodulatory properties. We have discovered that low concentrations of DNCB completely inactivated human or bovine thioredoxin reductase, with a second order rate constant in excess of 200 M-1 s-1, which is almost 10,000-fold faster than alkylation of GSH. Total inactivation of 50 nM reduced thioredoxin reductase was obtained by 100 microM DNCB after 5 reductase was obtained by 100 microM DNCB after 5 min of incubation at 20 degrees C also in the presence of 1 mM GSH. The inhibition occurred with enzyme only in the presence of NADPH and persisted after removal of DNCB, suggesting alkylation of the active site nascent thiols as the mechanism of inactivation. Thioredoxin reductase modified by DNCB lacked reducing activity with oxidized thioredoxin, 5,5'-dithiobis-(2-nitrobenzoic acid), or sodium selenite. However, the DNCB modified enzyme oxidized NADPH at a rate of 4.7 nmol/min/nmol of enzyme in the presence of atmospheric oxygen. This activity was not dependent on the presence of DNCB in solution and constituted a 34-fold increase of the inherent low NADPH oxidase activity of the native enzyme. DNCB is a specific inhibitor of mammalian thioredoxin reductase, which reacted 100-fold faster than glutathione reductase. The inactivation of the disulfide reducing activity of thioredoxin reductase and thioredoxin with a concomitant large increase of the NADPH oxidase activity producing reactive oxygen intermediates may mediate effects of DNCB on cells in vivo. PMID- 7876081 TI - Alpha 2 adrenergic receptor subtypes expressed in Chinese hamster ovary cells activate differentially mitogen-activated protein kinase by a p21ras independent pathway. AB - Epinephrine stimulation of rat alpha 2D, alpha 2B, and alpha 2C adrenergic receptor subtypes, expressed stably in Chinese hamster ovary (CHO) cells, caused a rapid, transient activation of mitogen-activated protein kinase (MAPK), with subtype-specific different efficiencies. The order of activation was CHO-2B approximately CHO-2D much greater than CHO-2C. Pertussis toxin blocked the stimulation of MAPK enzymatic activity and the parallel MAPK phosphorylation, demonstrating that these responses are mediated by pertussis toxin-sensitive Gi proteins. Contrary to what has been reported for the alpha 2A subtype expressed in rat-1 fibroblasts, epinephrine did not cause any detectable activation of p21ras in the CHO transfectants. Furthermore, combined application of epinephrine and phorbol myristate acetate had a potent cooperative but not additive effect in clones CHO-2D and CHO-2B but not in CHO-2C, suggesting that protein kinase C is probably differently involved in the signaling by the three alpha 2 receptor subtypes. These results show that in CHO cells, the different alpha 2 adrenergic receptor subtypes utilize differential pathways to activate MAPK in a p21ras independent way. PMID- 7876080 TI - The Bcl-2 oncoprotein functions as a pro-oxidant. AB - The mechanism by which the bcl-2 oncogene exerts its anti-apoptotic and antioxidant action is unknown. We found that expression of bcl-2 in superoxide dismutase-deficient (SOD-) Escherichia coli resulted in increased transcription of the KatG catalase-peroxidase, a 13-fold increase in KatG activity and a 100 fold increase in resistance to hydrogen peroxide. In addition, mutation rate was increased 3-fold, and katG and oxyR, a transcriptional regulator of katG induction, were required for aerobic survival. These data indicate that Bcl-2 acts as a pro-oxidant in E. coli, i.e. Bcl-2 generates reactive oxygen intermediates. In support of a pro-oxidant mechanism in eukaryotic cells, we found a 73% increase in superoxide dismutase activity in a murine B-cell line overexpressing Bcl-2. Increases in reduced glutathione and in oxyradical damage to DNA, previously observed in other overexpressing cell lines, are additional evidence for a pro-oxidant mechanism. Thus, Bcl-2 does not appear to be an antioxidant. Instead, Bcl-2 appears to influence levels of reactive oxygen intermediates that induce endogenous cellular antioxidants. This activity of Bcl 2 may control entry into apoptosis. PMID- 7876082 TI - A DNA polymerase beta in the mitochondrion of the trypanosomatid Crithidia fasciculata. AB - We previously purified a Crithidia fasciculata mitochondrial DNA polymerase that has unusual properties. Unlike a conventional mitochondrial DNA polymerase gamma, this enzyme is small, non-processive, deficient in 3'-exonuclease activity, and error prone (Torri, A. F., Kunkel, T. A., and Englund, P. T. (1994) J. Biol. Chem. 269, 8165-8171). In all of these characteristics, the enzyme resembles DNA polymerase beta, a nuclear enzyme thought to be involved in DNA repair. We have now cloned and sequenced the gene for this enzyme. The mitochondrial polymerase has significant homology, about 33% identity at the amino acid level, with human DNA polymerase beta. However, sequence analysis of the clone revealed the presence of a cleaved N-terminal presequence, presumably a mitochondrial import signal, which resembles presequences on other C. fasciculata mitochondrial proteins. The polymerase's function may be to repair the many gaps in newly replicated kinetoplast (mitochondrial) DNA minicircles in this parasite. This enzyme is the first example of a mitochondrial DNA polymerase beta. PMID- 7876083 TI - Action potential-induced quantal secretion of catecholamines from rat adrenal chromaffin cells. AB - Using single rat adrenal chromaffin cells, we examined the coupling of action potential activity to quantal release of catecholamines by combining perforated patch current-clamp recording with electrochemical microcarbon fiber amperometry. Chromaffin cells display steeper dependence of quantal release on action potential frequency than many nerve terminals, as well as more desynchronized release following an action potential. Also in contrast to neurons, in chromaffin cells, a major chemical secretagogue (acetylcholine) triggers potent quantal release even in the absence of electrical activity. These findings are consistent with an hypothesis that a major component of exocytosis from chromaffin cells involves diffusion of Ca2+ to secretion sites which are less well co-localized with Ca2+ channels than those in nerve terminals. PMID- 7876084 TI - Cytochrome P-450TYR is a multifunctional heme-thiolate enzyme catalyzing the conversion of L-tyrosine to p-hydroxyphenylacetaldehyde oxime in the biosynthesis of the cyanogenic glucoside dhurrin in Sorghum bicolor (L.) Moench. AB - Cytochrome P-450TYR, which catalyzes the N-hydroxylation of L-tyrosine in the biosynthesis of the cyanogenic glucoside dhurrin in Sorghum bicolor (L.) Moench has recently been isolated (Sibbesen, O., Koch, B., Halkier, B. A., and Moller, B. L. (1994) Proc. Natl. Acad. Sci. U.S.A. 92, 9740-9744). Reconstitution of the enzyme activity in lipid micelles containing cytochrome P-450TYR and NADPH cytochrome P-450 oxidoreductase demonstrates that cytochrome P-450TYR catalyzes the conversion of L-tyrosine into p-hydroxyphenylacetaldehyde oxime. Earlier studies with microsomes have demonstrated that this conversion involves two N hydroxylation reactions of which the first produces N-hydroxytyrosine. We propose that the product of the second N-hydroxylation reaction is N,N-dihydroxytyrosine. N,N-dihydroxytyrosine is dehydrated to 2-nitroso-3-(p-hydroxyphenyl) propionic acid which decarboxylates to p-hydroxyphenylacetaldehyde oxime. The dehydration and decarboxylation reactions may proceed non-enzymatically. The E/Z ratio of the p-hydroxyphenylacetaldehyde oxime produced by reconstituted cytochrome P-450TYR is 69:31. Lipid micelles made from L-alpha-dilauroyl phosphatidylcholine are more than twice as effective in reconstituting cytochrome P-450TYR activity as compared to other lipids. The Km and turnover number of the enzyme is 0.14 mM and 200 min-1, respectively, when assayed in the presence of 15 mM NaCl whereas the values are 0.21 mM and 230 min-1 when assayed in the absence of added salt. The multifunctional nature cytochrome P-450TYR is confirmed by demonstrating that binding of L-tyrosine or N-hydroxytyrosine mutually excludes binding of the other substrate. These results explain why the conversion of tyrosine to p hydroxyphenylacetaldehyde oxime as earlier reported (Moller, B. L., and Conn, E. E. (1980) J. Biol. Chem. 255, 3049-3056) shows the phenomenon of catalytic facilitation ("channeling"). Cytochrome P-450TYR is the first isolated multifunctional heme-thiolate enzyme from plants. N-Hydroxylases of the cytochrome P-450 type with high substrate specificity have not previously been reported. PMID- 7876085 TI - Characterization and comparison of the interleukin 13 receptor with the interleukin 4 receptor on several cell types. AB - We describe here the characterization of the interleukin (IL) 13 receptor and a comparison with the IL-4 receptor on different cell types. Several, but not all, of the IL-4 receptor-positive cells showed specific IL-13 binding, which was always completely displaced by IL-4. In the IL-13 receptor-positive cells, the IL 13 either completely or partially displaced the labeled IL-4. Further characterization of the IL-13 receptor in two cell lines, COS-3 and A431, representative of the groups of complete and partial displacement of IL-4 by IL 13, respectively, showed that the IL-13 binds with high affinity (Kd approximately 300 pM) to both cells and that the number of binding sites is, in COS-3 cells, equivalent to that for IL-4 and, in A431 cells, is smaller than that for IL-4. Cross-linking of labeled IL-13 yielded, on COS-3 cells, two affinity labeled complexes of 220 and 70 kDa, and on A431 cells, one complex of 70 kDa; labeled IL-4 yielded on both cells the same pattern of three complexes of 220, 145, and 70 kDa. Altogether, these results suggest that the IL-13 receptor may be constituted by a subset of the IL-4 receptor complex associated with at least one additional protein. PMID- 7876086 TI - Conodipine-M, a novel phospholipase A2 isolated from the venom of the marine snail Conus magus. AB - We describe the purification and first biochemical characterization of an enzymatic activity in venom from the marine snail Conus magus. This enzyme, named conodipine-M, is a novel phospholipase A2 with a molecular mass of 13.6 kDa and is comprised of two polypeptide chains linked by one or more disulfide bonds. The amino acid sequence of conodipine-M shows little if any homology to other previously sequenced phospholipase A2 enzymes (PLA2s). Conodipine-M thus represents a new group of PLA2s. This is remarkable, since conodipine-M displays a number of properties that are similar to those of previously characterized 14 kDa PLA2s. The enzyme shows little, if any, phospholipase A1, diacyglycerol lipase, triacylglycerol lipase, or lysophospholipase activities. Conodipine-M hydrolyzes the sn-2 ester of various preparations of phospholipid only in the presence of calcium and with specific activities that are comparable to those of well known 14-kDa snake venom and pancreatic PLA2s. The Conus enzyme binds tightly to vesicles of the negatively charged phospholipid 1,2-dimyristoyl-sn glycero-3-phosphomethanol and catalyzes the hydrolysis of this substrate in a processive fashion. Conodipine-M does not significantly discriminate against phospholipids with unsaturated versus saturated fatty acids at the sn-2 position or with different polar head groups. Linoleoyl amide and a phospholipid analog containing an alkylphosphono group at the sn-2 position are potent inhibitors of conodipine-M. We suggest that the functional resemblance of conodipine-M to other PLA2s might be explained by the utilization of similar catalytic residues. PMID- 7876087 TI - The transcriptional regulatory protein, YB-1, promotes single-stranded regions in the DRA promoter. AB - YB-1 is a member of a newly defined family of DNA- and RNA-binding proteins, the Y box factors. These proteins have been shown to affect gene expression at both the transcriptional and translational levels. Recently, we showed that YB-1 represses interferon-gamma-induced transcription of class II human major histocompatibility (MHC) genes (1). Studies in this report characterize the DNA binding properties of purified, recombinant YB-1 on the MHC class II DRA promoter. The generation of YB-1-specific antibodies further permitted an analysis of the DNA binding properties of endogenous YB-1. YB-1 specifically binds single-stranded templates of the DRA promoter with greater affinity than double-stranded templates. The single-stranded DNA binding sites of YB-1 were mapped to the X box, whereas the double-stranded binding sites were mapped to the Y box of the DRA promoter, by methylation interference analysis. Most significantly, YB-1 can induce or stabilize single-stranded regions in the X and Y elements of the DRA promoter, as revealed by mung bean nuclease analysis. In concert with the findings that YB-1 represses DRA transcription, this study of YB 1 binding properties suggests a model of repression in which YB-1 binding results in single-stranded regions within the promoter, thus preventing loading and/or function of other DRA-specific transactivating factors. PMID- 7876088 TI - Cloning and molecular characterization of hxA, the gene coding for the xanthine dehydrogenase (purine hydroxylase I) of Aspergillus nidulans. AB - We have cloned and sequenced the hxA gene coding for the xanthine dehydrogenase (purine hydroxylase I) of Aspergillus nidulans. The gene codes for a polypeptide of 1363 amino acids. The sequencing of a nonsense mutation, hxA5, proves formally that the clones isolated correspond to the hxA gene. The gene sequence is interrupted by three introns. Similarity searches reveal two iron-sulfur centers and a NAD/FAD-binding domain and have enabled a consensus sequence to be determined for the molybdenum cofactor-binding domain. The A. nidulans sequence is a useful outclass for the other known sequences, which are all from metazoans. In particular, it gives added significance to the missense mutations sequenced in Drosophila melanogaster and leads to the conclusion that while one of the recently sequenced human genes codes for a xanthine dehydrogenase, the other one must code for a different molybdenum-containing hydroxylase, possibly an aldehyde oxidase. The transcription of the hxA gene is induced by the uric acid analogue 2 thiouric acid and repressed by ammonium. Induction necessitates the product of the uaY regulatory gene. PMID- 7876089 TI - ERGIC-53, a membrane protein of the endoplasmic reticulum-Golgi intermediate compartment, is identical to MR60, an intracellular mannose-specific lectin of myelomonocytic cells. AB - A mannose-specific membrane lectin (MR60) isolated from human myelomonocytic HL60 cells by affinity chromatography is expressed in intracellular organelles of immature monocytes (Pimpaneau, V., Midoux, P., Monsigny, M., and Roche, A. C. (1991) Carbohydr. Res. 213, 95-108). It is not present at the cell surface and is immunochemically and structurally distinct from the M(r) 175,000 mannose receptor of mature macrophages. MR60 cDNA was isolated and characterized; on the basis of its sequence, MR60 is not related to any known mammalian lectins. Surprisingly, MR60 was found to be identical to ERGIC-53 (Schindler, R., Itin, C., Zerial, M., Lottspeich, F., and Hauri, H.P. (1993) Eur. J. Cell Biol. 61, 1-9), a type I integral membrane protein, defined as a marker of the intermediate compartment that recycles between the Golgi apparatus and endoplasmic reticulum; MR60/ERGIC 53 shares with VIP-36 significant homologies with leguminous plant lectins (Fiedler, K., and Simmons, K. (1994) Cell 77, 625-626). We extend these findings in evidencing a structural homology between MR60/ERGIC-53 and mammalian galectins (soluble beta galactose binding proteins). MR60/ERGIC-53 is the first lectin characterized as an endoplasmic reticulum-Golgi protein. Accordingly, this intracellular mannose binding protein could be involved in the traffic of glycoproteins between endoplasmic reticulum and the Golgi apparatus. PMID- 7876090 TI - Gs couples thyrotropin-releasing hormone receptors expressed in Xenopus oocytes to phospholipase C. AB - Coupling of thyrotropin-releasing hormone (TRH) receptors to individual G proteins has been studied in Xenopus oocytes injected with receptor cRNA and antisense oligonucleotides to mRNA encoding different G-protein alpha- and beta subunits. Injection of antisenses which target mRNA sequences shared by several G protein alpha or beta gamma polypeptides effectively blocked Ca(2+)-dependent Cl- currents induced by TRH through activation of phospholipase C. Three different alpha s-specific antisense oligonucleotides complementary to sequences located in different positions along the coding region of the alpha s protein mRNA were highly effective in inhibiting TRH-induced responses. Anti-alpha o, -alpha q, alpha i, or -alpha z oligonucleotides were not able to modify the TRH-evoked response. In contrast, anti-alpha o, but not anti-alpha s, oligonucleotides blocked the response to serotonin in oocytes injected with serotonin 5-HT1c receptor cRNA. Cholera toxin catalyzed the [32P]ADP-ribosylation of 40-42- and 50 52-kDa proteins in GH3 cell plasma membranes. [32P]ADP-ribosylation of oocyte membranes with the toxin labeled several proteins. These include a single 50-55 kDa substrate, which is clearly diminished in membranes from anti-alpha s injected oocytes. Amplification of oocyte RNA in a polymerase chain reaction system and sequencing of the amplified products demonstrated that anti-alpha s oligonucleotides selectively recognize the message for the Xenopus alpha s polypeptide. It is concluded that Gs, but not Go, Gq, Gi, or Gz, couples TRH receptors expressed in oocytes to activation of phospholipase C and subsequent inositol 1,4,5-trisphosphate-dependent stimulation of Ca(2+)-dependent Cl- currents. PMID- 7876091 TI - Interaction of the hemolytic lectin CEL-III from the marine invertebrate Cucumaria echinata with the erythrocyte membrane. AB - CEL-III is one of four Ca(2+)-dependent galactose/N-acetylgalactosamine (GalNAc) binding lectins from the marine invertebrate Cucumaria echinata which exhibits hemolytic activity, especially toward rabbit and human erythrocytes. The hemolytic activity of CEL-III was also Ca(2+)-dependent and was found to be inhibited by galactose or GalNAc-containing carbohydrates, suggesting that the hemolysis was caused by CEL-III binding to specific carbohydrates on the erythrocyte membrane by Ca(2+)-dependent lectin activity, followed by partial destruction of the membrane. The activity of CEL-III was highest at 10 degrees C and decreased markedly with increasing temperature, unlike usual enzymatic reactions. The hemolytic activity of CEL-III increased with increasing pH from neutral to 10, but almost no hemolysis was observed below pH 6.5. Immunoblotting analysis of proteins from the erythrocyte membrane after treatment with CEL-III indicated that CEL-III aggregates were irreversibly bound to the membrane. When erythrocytes were incubated with CEL-III in the presence of dextran with molecular masses greater than 4 kDa, lysis was impeded considerably, while a concomitant release of ATP was detected from these osmotically protected cells. It was found that CEL-III released carboxyfluorescein from artificial globoside containing lipid vesicles, and it is suggested that CEL-III is a novel pore forming protein with the characteristics of a Ca(2+)-dependent lectin, which may act as a toxic protein to foreign microorganisms. PMID- 7876092 TI - Characterization of sorting signals in the beta-amyloid precursor protein cytoplasmic domain. AB - The beta-amyloid precursor protein (APP) is proteolytically processed to generate beta-amyloid protein, the principal protein component of neuropathological lesions characteristic of Alzheimer's disease. To investigate potential sorting signals in the cytoplasmic tail of APP, we transplanted APP cytoplasmic tail sequences into the cytoplasmic tail of the human transferrin receptor (TR) and showed that two sequence motifs from the APP cytoplasmic tail promote TR internalization. One sequence, GYENPTY, is related to the low density lipoprotein receptor internalization signal, FDNPVY, but also involves a critical glycine residue; the other, YTSI, conforms to the 4-residue tyrosine-based internalization signal consensus sequence. Furthermore, a chimeric molecule (APP TR) consisting of the cytoplasmic domain of APP and the transmembrane and external domains of TR was rapidly internalized enabling the transport of iron into the cell at approximately 50% the rate of wild-type TR. Alanine scanning mutations indicated that the two sequences identified in transplantation experiments were required for internalization of the chimera. Metabolic pulse chase experiments showed that the APP-TR chimeras were degraded in a post-Golgi membrane compartment within 2-4 h following normal glycosylation. Degradation was partially dependent upon the two internalization signals and was inhibited by ammonium chloride. A fraction of APP-TR chimeras traffic to a degradative endocytic compartment after appearing on the cell surface. Comparison of soluble APP released from cells expressing either full-length human APP or mutant APP with the sequence YENPTY deleted indicated that this sequence is required for sorting of full-length APP along similar trafficking pathways as the APP-TR chimera. PMID- 7876093 TI - Identification of a protein with homology to hsp90 that binds the type 1 tumor necrosis factor receptor. AB - The yeast-based two hybrid has been used to identify a novel protein that binds to the intracellular domain of the type 1 receptor for tumor necrosis factor (TNFR-1IC). The TNF receptor-associated protein, TRAP-1, shows strong homology to members of the 90-kDa family of heat shock proteins. After in vitro transcription/translation and 35S labeling, TRAP-1 was precipitated using a fusion protein consisting of glutathione S-transferase and TNFR-1IC, showing that the two proteins directly interact. The ability of deletion mutants of TNFR-1 to interact with TRAP-1 was tested using the two hybrid system. This showed that the amino acid sequences that mediate binding are diffusely distributed outside of the domain in the C terminus of TNFR-1IC that signals cytotoxicity. The 2.4 kilobase TRAP-1 mRNA was variably expressed in skeletal muscle, liver, heart, brain, kidney, pancreas, lung, and placenta. TRAP-1 mRNA was also detected in each of eight different transformed cell lines. Identification of TRAP-1 may be an important step toward defining how TNFR-1, which does not contain protein tyrosine kinase activity, transmits its message to signal transduction pathways. PMID- 7876094 TI - Differentiation- and protein kinase C-dependent regulation of alanine transport via system B. AB - The regulation of sodium-dependent L-alanine transport is described for the first time in intestinal cells. Substrate analogue inhibition patterns and Dixon analyses indicated that uptake occurred via transport system B, an epithelial cell variant of systems B0,+ and ASC. System B served > 95% of the Na(+) dependent alanine uptake in both undifferentiated (2 days postpassaging) and differentiated (> 9 days postpassaging) states of the human Caco-2 cultured intestinal cell line. (Methylamino)isobutyric acid-inhibitable system A transport accounted for < 5% of total alanine uptake. System B activity was greater in undifferentiated cells compared with the differentiated state, and activity at any differentiation state was stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA). The maximal stimulation, determined by TPA dose-response/exposure time data, was attributable to a change in cell transport capacity (Vmax), with Km unaffected. The Vmax of system B was greater in 2-day-old cells (2.79 +/- 0.21 nmol min-1 mg of protein-1; Km = 164 +/- 26 microM alanine), decreasing to Vmax = 0.51 +/- 0.03 nmol min-1 mg of protein-1 (Km = 159 +/- 14 microM) in 9-day-old cells. Regardless of differentiation status, the sodium-activation Hill coefficient was 1.06 +/- 0.10, and the alanine passive diffusion permeability coefficient was 0.53 +/- 0.08 microliter min-1 mg of protein-1. Phorbol ester up regulated the Vmax of system B in 2-day-old cells to Vmax = 6.32 +/- 0.37 nmol min-1 mg of protein-1 (Km = 169 +/- 18 microM), and in 9-day-old cells to Vmax = 1.42 +/- 0.05 nmole min-1 mg of protein-1 (Km = 180 +/- 10 microM). Phorbol ester stimulation of transport occurred after at least 6 h of continual exposure, and was blocked by the protein kinase C inhibitors chelerythrine or photoactivated calphostin C. Protein synthesis inhibitors cycloheximide and actinomycin D each blocked the phorbol ester up-regulation of system B activity. It is concluded that Caco-2 cells regulate carrier-mediated sodium-dependent transport of L alanine by changing the membrane capacity to transport alanine via system B and that this regulation involves de novo protein synthesis under the control of protein kinase C. PMID- 7876095 TI - Multiple canalicular transport mechanisms for glutathione S-conjugates. Transport on both ATP- and voltage-dependent carriers. AB - A large number of structurally distinct electrophiles are conjugated to glutathione within hepatocytes, and the resulting glutathione S-conjugates are selectively transported across the canalicular membrane into bile. To test the hypothesis that a single multi-specific, ATP-dependent carrier mediates biliary secretion of glutathione S-conjugates, the present study compared the driving forces and substrate specificity for canalicular transport of S-ethylglutathione (ethyl-SG), a low molecular weight and relatively hydrophilic thioether, and S (2,4-dinitrophenyl)-glutathione (DNP-SG), a larger and more hydrophobic anion, using isolated rat liver canalicular membrane vesicles. In agreement with previous findings, DNP-SG transport was stimulated by ATP, although there was considerable transport in the absence of ATP. ATP-independent DNP-SG transport was unaffected by a Na+ gradient, was enhanced by a valinomycin-induced K+ diffusion potential, and was saturable, with both high affinity (Km = 8 +/- 2 microM) and low affinity (Km = 0.5 +/- 0.1 mM) components. High affinity ATP independent DNP-SG uptake was cis-inhibited by GSH, GSH monoethyl ester, glutathione S-conjugates, other gamma-glutamyl compounds, sulfobromophthalein, and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). In contrast, ATP dependent DNP-SG uptake was unaffected by GSH, GSH ester, S-methyl glutathione, or S-carbamidomethyl glutathione, but was strongly inhibited by sulfobromophthalein, DIDS, and by high molecular weight and relatively hydrophobic glutathione S-conjugates. Transport of the low molecular weight ethyl SG conjugate was only minimally stimulated by ATP (10-20%). ATP-independent ethyl SG uptake was electrogenic, saturable (Km = 10 +/- 1 microM) and was inhibited by GSH and all glutathione S-conjugates tested. These findings indicate the presence of multiple canalicular transport mechanisms for glutathione S-conjugates and demonstrate that the physicochemical properties of the S moiety are major determinants of transport. Relatively high molecular weight hydrophobic conjugates are substrates for both ATP-dependent and -independent mechanisms, whereas low molecular weight glutathione S-conjugates are transported largely by electrogenic carriers. PMID- 7876096 TI - Transcriptional regulation of the carcinoembryonic antigen gene. Identification of regulatory elements and multiple nuclear factors. AB - Human carcinoembryonic antigen (CEA) belongs to a family of membrane glycoproteins that are overexpressed in many carcinomas; CEA functions in vitro as a homotypic intercellular adhesion molecule and can inhibit differentiation when expressed ectopically in myoblasts. The regulation of expression of CEA is therefore of considerable interest. The CEA gene promoter region between -403 and -124 base pairs upstream of the translation initiation site directed high levels of expression in CEA-expression SW403 cells and was 3 times more active in differentiated than in undifferentiated Caco-2 cells, correlating exactly with the 3-fold increase in CEA mRNA seen in differentiated Caco-2 cells. Inclusion of additional upstream sequences between -1098 and -403 base pairs repressed all activity. By in vitro footprinting and deletion analyses, four cis-acting elements were mapped within the positive regulatory region, and one element within the silencing region. Several nuclear factors binding to these domains were identified: USF, Sp1, and an Sp1-like factor. By co-transfection, USF directly activated the CEA gene promoter in vivo in both SW403 and Caco-2 cells. In addition, the levels of factors binding to each positively acting element increased dramatically with differentiation in Caco-2 cells. Thus the transcriptional control of the CEA gene depends on the interaction of several regulatory elements that bind multiple specific factors. PMID- 7876097 TI - Identification of the potential active site of the signal peptidase SipS of Bacillus subtilis. Structural and functional similarities with LexA-like proteases. AB - Signal peptidases remove signal peptides from secretory proteins. By comparing the type I signal peptidase, SipS, of Bacillus subtilis with signal peptidases from prokaryotes, mitochondria, and the endoplasmic reticular membrane, patterns of conserved amino acids were discovered. The conserved residues of SipS were altered by site-directed mutagenesis. Replacement of methionine 44 by alanine yielded an enzyme with increased activity. Two residues (aspartic acid 146 and arginine 84) appeared to be conformational determinants; three other residues (serine 43, lysine 83, and aspartic acid 153) were critical for activity. Comparison of SipS with other proteases requiring serine, lysine, or aspartic acid residues in catalysis revealed sequence similarity between the region of SipS around serine 43 and lysine 83 and the active-site region of LexA-like proteases. Furthermore, self-cleavage sites of LexA-like proteases closely resembled signal peptidase cleavage sites. Together with the finding that serine and lysine residues are critical for activity of the signal peptidase of Escherichia coli (Tschantz, W.R., Sung, M., Delgado-Partin, V.M., and Dalbey, R.E. (1993) J. Biol. Chem. 268, 27349-27354), our data indicate that type I signal peptidases and LexA-like proteases are structurally and functionally related serine proteases. A model envisaging a catalytic serine-lysine dyad in prokaryotic type I signal peptidases is proposed to accommodate our observations. PMID- 7876098 TI - Nuclear export pathways of tRNA and 40 S ribosomes include both common and specific intermediates. AB - Different classes of RNAs are exported from Xenopus laevis oocyte nuclei by facilitated pathways. We have performed kinetic competition analyses to investigate the relationship between the export pathways of microinjected tRNA and ribosomal subunits. Saturating concentrations of ribosomal subunits do not compete tRNA export. Thus, the saturable factor in the ribosomal subunit export pathway is not limiting for tRNA export. The co-microinjection of ribosomal subunits did, however, stimulate the rate of tRNA export. Co-injected mRNA also stimulated tRNA export. tRNA export itself displays positive cooperative export kinetics that are abrogated by saturating concentrations of rRNA. These results are consistent with the existence of common high affinity RNA-binding sites that can be titrated with tRNA, rRNA or ribosomal subunits, and mRNA. Furthermore, high concentrations of tRNA are also shown to have moderate inhibitory effects on 40 S subunit export, indicating a lower affinity common intermediate also shared by mRNA. PMID- 7876100 TI - Characterization of a HeLa cell factor which negatively regulates transcriptional activation in vitro by transcriptional enhancer factor-1 (TEF-1). AB - A novel negatively acting factor has been identified and partially purified from HeLa and BJA-B cell extracts by chromatographic fractionation. Addition of this factor to HeLa cell extracts or to a reconstituted HeLa cell transcription system repressed transcriptional activation by a chimeric activator, GAL-TEF-1, containing the activation function of transcriptional enhancer factor-1 (TEF-1). In contrast, this factor did not repress transactivation by the chimeric GAL-VP16 activator. Repression of transactivation by GAL-TEF-1 could be alleviated by the addition of immunopurified HeLa cell TFIID, but not by increased quantities of GAL-TEF-1. These observations suggest that this negatively acting factor represses transactivation by interfering with the function of, or competing for, the TATA-binding protein-associated coactivators which mediate the activity TEF 1. PMID- 7876099 TI - Expression and kinetic characterization of recombinant human stomach alcohol dehydrogenase. Active-site amino acid sequence explains substrate specificity compared with liver isozymes. AB - A full-length 1966-base pair clone of the human class IV alcohol dehydrogenase (sigma-ADH) was isolated from a human stomach cDNA library. The 373-amino acid sigma-ADH encoded by this cDNA was expressed in Escherichia coli. The specific activity of the recombinant enzyme for ethanol oxidation at pH 7.5 and 25 degrees C, calculated from active-site titration of NADH binding, was 92 +/- 9 units/mg. Kinetic analysis of the catalytic efficiency (kcat/KM) of recombinant sigma-ADH for oxidation of primary alcohols indicated broad substrate specificity. Recombinant human sigma-ADH exhibited high catalytic efficiency for oxidation of all-trans-retinol to all-trans-retinal. This pathway is important in the synthesis of the transcriptional regulator all-trans-retinoic acid. Secondary alcohols and 3 beta-hydroxysteroids were inactive with sigma-ADH or were oxidized with very low efficiency. The KM of sigma-ADH for ethanol was 25 mM, and the KM for primary straight chain alcohols decreased substantially as chain length increased. There are important amino acid differences in the alcohol-binding site between the human class IV (sigma) and human class I (beta) alcohol dehydrogenases that appear to explain the high catalytic efficiency for all-trans retinol, the high kcat for ethanol, and the low catalytic efficiency for secondary alcohols of sigma-ADH relative to beta 1-ADH. For example, modeling the binding of all-trans-retinol in the human beta 1-ADH structure suggested that coordination of retinol to the active-site zinc is hindered by a loop from residues 114 to 120 that is at the entrance to the alcohol-binding site. The deletion of Gly-117 in human sigma-ADH and a substitution of Leu for the bulky Tyr-110 appear to facilitate retinol access to the active-site zinc. PMID- 7876101 TI - Molecular basis of IsK protein regulation by oxidation or chelation. AB - Slowly activating IsK channels were expressed in Xenopus oocytes and exposed to oxidative agents. Oxidative treatment reduced the resulting current IsK, while no inhibition was observed for IsK protein mutants carrying a Ser mutation instead of a highly conserved Cys residue in the intracellular domain. In contrast, Hg2+, which may not only oxidize thiol groups but also form chelates with dibasic amino acids, caused a use-dependent, positive regulation of IsK. This effect was reversed in an IsK protein mutant with a deletion in the extracellular domain. These data suggest opposite effects of peroxides and Hg2+ on IsK, a peroxide mediated IsK inhibition by intracellular oxidation and a Hg(2+)-mediated IsK increase, caused by extracellular Hg2+ chelation of the IsK protein. PMID- 7876102 TI - Protein kinase C and mitogen-activated protein kinase are required for 1,25 dihydroxyvitamin D3-stimulated Egr induction. AB - Recent studies have demonstrated that 1,25-dihydroxyvitamin D3 (D3) can activate Raf kinase and induce Egr expression in cultured rat hepatic Ito cells (Lissoos, T. W., Beno, D. W. A., and Davis, B. H. (1993) J. Biol. Chem. 268, 25132-25138). Since Raf is an upstream activator of mitogen-activated protein kinase (MAPK), the current study evaluated the ability of D3 to activate MAPK. D3-activated MAPK and induced its cytoplasmic to perinuclear translocation in Ito cells. MAPK activation was found to be protein kinase C-dependent, which was analogous to previous studies of D3 and Raf activation. To further explore the D3 cascade, a series of transient transfections were performed using dominant negative raf and MAPK mutant plasmids which effectively block Ras-induced Raf and MAPK activity, respectively. D3 induced a marked increase in the expression of a chloramphenicol acetyltransferase reporter gene linked to the Egr promoter (egr-CAT). When the dominant negative Raf plasmid was co-transfected, there was no significant reduction in egr-CAT. In contrast, when the dominant negative MAPK plasmid was co transfected, egr-CAT induction was completely abolished. These results suggest that 1) D3 stimulates MAPK via a protein kinase C-dependent pathway, 2) D3 induced Egr expression can occur via a pathway independent of Ras-induced Raf, and 3) D3 absolutely requires MAPK activity for Egr expression. PMID- 7876103 TI - The role of cleavage of the light chain at positions Arg1689 or Arg1721 in subunit interaction and activation of human blood coagulation factor VIII. AB - The role of Factor VIII light chain cleavage in Factor VIII activation and subunit interaction was investigated. Purified Factor VIII was dissociated into its separate subunits, and the isolated light chain was cleaved by thrombin at position Arg1689 or by Factor Xa at position Arg1721. These Factor VIII light chain derivatives then were used for reconstitution with purified Factor VIII heavy chain to obtain heterodimers that were exclusively cleaved within the light chain. Intact and cleaved light chain could effectively be reassociated with heavy chain, with concomitant regain of Factor VIII cofactor function. The association rate constant of Factor Xa-cleaved light chain was found to be 3-fold lower than that of thrombin-cleaved or intact light chain, suggesting a role of the region Ser1690-Arg1721 in subunit assembly. Dissociation rate constants, however, were independent of Factor VIII light chain cleavage. Low ionic strength was observed to promote association but to destabilize the Factor VIII heterodimer. At high ionic strength, Factor VIII dissociation was extremely slow (kappa off approximately 10(-5) s-1) for all Factor VIII light chain derivatives, indicating that Factor VIII light chain cleavage is not related to Factor VIII dissociation. Furthermore, Factor VIII light chain cleavage does not affect enzyme-cofactor assembly, since the various light chain derivatives proved equally efficient in binding to Factor IXa (Kd approximately 15 nM). Studies in a purified Factor X-activating system demonstrated that thrombin and Factor Xa activate Factor VIII to the same extent. However, Factor Xa differed from thrombin in that it cleaved at Arg1721 rather than at Arg1689. Reassociated heterodimers of Factor VIII heavy chain and intact light chain did not promote Factor X activation. In contrast, heterodimers that contained cleaved light chain exhibited substantial Factor VIIIa activity. These data demonstrate that a single cleavage at either Arg1689 or Arg1721 converts the inactive Factor VIII heterodimer into an active cofactor of Factor IXa. PMID- 7876104 TI - The hemoregulatory peptide N-acetyl-Ser-Asp-Lys-Pro is a natural and specific substrate of the N-terminal active site of human angiotensin-converting enzyme. AB - Angiotensin I-converting enzyme (ACE) is a zinc-dipeptidyl carboxypeptidase, which contains two similar domains, each possessing a functional active site. Respective involvement of each active site in the degradation of the circulating peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), a negative regulator of hematopoietic stem cell proliferation, was studied by using wild-type recombinant ACE and two full-length mutants containing a single functional site. Both the N- and C-active sites of ACE exhibit dipeptidyl activity toward AcSDKP, with Km values of 31 and 39 microM, respectively. However, the N-active site hydrolyzes the peptide 50 times faster compared with the C-active site, with kcat/Km values of 0.5 and 0.01 microM-1.s-1, respectively. The predominant role of the N-active site in AcSDKP hydrolysis was confirmed by the inhibition of hydrolysis using a monoclonal antibody specifically directed against the N-active site. The N-domain specificity for AcSDKP will aid the identification of specific inhibitors for this domain. This is the first report of a highly specific substrate for the N active site of ACE, with kinetic constants in the range of physiological substrates, suggesting that ACE might be involved via its N-terminal active site in the in vivo regulation of the local concentration of this hemoregulatory peptide. PMID- 7876105 TI - Regulation of phosphatidylinositol 3'-kinase by tyrosyl phosphoproteins. Full activation requires occupancy of both SH2 domains in the 85-kDa regulatory subunit. AB - Phosphatidylinositol 3'-kinase (PI 3'-kinase) is activated in insulin-stimulated cells by the binding of the SH2 domains in its 85-kDa regulatory subunit to insulin receptor substrate-1 (IRS-1). We have previously shown that both tyrosyl phosphorylated IRS-1 and mono-phosphopeptides containing a single YXXM motif activate PI 3'-kinase in vitro. However, activation by the monophosphopeptides was significantly less potent than activation by the multiply phosphorylated IRS 1. We now show that the increased potency of PI 3'-kinase activation by IRS-1 relative to phosphopeptide is not due to tertiary structural features IRS-1, as PI 3'-kinase is activated normally by denatured, reduced, and carboxymethylated IRS-1. Furthermore, activation of PI 3'-kinase by bis-phosphorylated peptides containing two YXXM motifs is 100-fold more potent than the corresponding mono phosphopeptides and similar to activation by IRS-1. These data suggest that tyrosyl-phosphorylated IRS-1 or bis-phosphorylated peptides bind simultaneously to both SH2 domains of p85. However, these data cannot differentiate between an activation mechanism that requires two-site occupancy for maximal activity as opposed to one in which bivalent binding enhances the occupancy of a single activating site. To distinguish between these possibilities, we produced recombinant PI 3'-kinase containing either wild-type p85 or p85 mutated in its N terminal, C-terminal, or both SH2 domains. We find that mutation of either SH2 domains significantly reduced phosphopeptide binding and decreased PI 3'-kinase activation by 50%, whereas mutation of both SH2 domains completely blocked binding and activation. These data provide the first direct evidence that full activation of PI 3'-kinase by tyrosylphosphorylated proteins requires occupancy of both SH2 domains in p85. PMID- 7876106 TI - Activation of the TSG-6 gene by NF-IL6 requires two adjacent NF-IL6 binding sites. AB - Tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6) encodes a protein expressed during inflammation. We have previously shown that transcription factors of the NF-IL6 and AP-1 families cooperatively modulate activation of the TSG-6 gene by TNF or interleukin 1 (IL-1) through a promoter region that contains an NF-IL6 site (-106 to -114) and an AP-1 element (-126 to -119). In this study we report the identification of an additional NF-IL6 site (NF-IL6*) located at positions 92 to -83. Footprinting and electrophoretic mobility shift assay suggested that NF-IL6 binds with higher affinity to the newly identified NF-IL6* site than to the earlier identified promoter-distal NF-IL6 site and that the two sites cooperate in binding NF-IL6. TNF and IL-1 stimulate specific binding of nuclear proteins to the NF-IL6* site more efficiently than to the promoter-distal NF-IL6 site. Moreover, a mutation in the NF-IL6* site abolished transactivation of the TSG-6 promoter by NF-IL6 despite the presence of the intact promoter-distal NF IL6 site. A mutation in the promoter-distal NF-IL6 site also greatly decreased activation of the TSG-6 promoter by NF-IL6. We conclude that the two NF-IL6 sites are functionally interdependent in the activation of the TSG-6 gene. PMID- 7876107 TI - An initiator element is required for maximal human chorionic somatomammotropin gene promoter and enhancer function. AB - Previous studies have indicated that cell-specific expression of the human chorionic somatomammotropin (hCS) gene may be mediated by a placental-specific enhancer (CSEn). In the current studies, we have analyzed the promoter elements that are required for enhancer and promoter function in choriocarcinoma cells (BeWo). Mutation of both hCS GHF1 sites had no effect on promoter or enhancer activity. In contrast, mutation of the Sp1 site diminished basal and CSEn stimulated transcription by approximately 75% and approximately 56%, respectively, indicating that Sp1 was necessary but not sufficient for maximal basal and enhancer-mediated transcription. Deletion and site-specific mutation of the proximal promoter region indicated that the TATA box and an initiator site (InrE) located between nucleotides -15/+1 of the hCS promoter were required for maximal promoter and enhancer function. Mutations of the InrE were associated with reduced basal and enhancer-stimulated activities and altered transcription initiation sites. A protein of 70-kDa mass, that was preferentially expressed in human choriocarcinoma cells (BeWo and JEG-3), bound specifically to the InrE. The data suggest that an initiator present in high concentrations in placental cells contributes to the control of cell-specific hCS gene expression at the promoter level and is required for maximal enhancer function. PMID- 7876108 TI - Stimulation of mitogen-activated protein kinase by thyrotropin in primary cultured human thyroid follicles. AB - In the thyroid, thyrotropin (TSH) stimulates both growth and function, and stimulates the production of cAMP which reproduces most of the effects of TSH. Here, we report evidence that TSH stimulates the mitogen-activated protein (MAP) kinase cascade through a cAMP-independent pathway, in human thyroid. TSH stimulated MAP kinase activity (4-9-fold the basal level) measured in the cytosolic fractions of primary cultured thyroid follicles. Maximal activity was reached after 20 min and remained sustained for 1-3 h, TSH being as potent as EGF; EC50 was 1.5 nM TSH. Only a single isoform of MAP kinase (p42) was detected in the follicles. p42 was phosphorylated on tyrosine residues and showed a reduced electrophoretic mobility in follicles stimulated by TSH. All these effects on MAP kinase were decreased by preincubation of the follicles with human anti-TSH receptor antibodies. The stimulation of MAP kinase by TSH was neither blocked by pertussis toxin nor reproduced by forskolin, cholera toxin, or 8-bromo cAMP. In conclusion, in human thyroid cells, in contrast with previous observations on dog thyroid cells, TSH stimulates strongly MAP kinase through a pertussis toxin-insensitive and cAMP-independent pathway. PMID- 7876109 TI - Mechanism of transferrin receptor down-regulation in K562 cells in response to protein kinase C activation. AB - Treatment with phorbol esters increases endocytosis of the transferrin receptor in K562 cells (Klausner, R. D., Harford, J., and van Renswoude, J. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 3005-3009). In this report, we demonstrate that this effect is reversible within early times of protein kinase C activation (< 2 h) but that prolonged exposure to phorbol esters results in a net loss of receptors. These effects are not due to the differentiation response of K562 cells to phorbol esters since bryostatin-1 also down-regulates the endocytosis of the transferrin receptor and shut downs receptor synthesis, but does not induce differentiation (Hocevar, B. A., Morrow, D. M., Tykocinski, M. L., and Fields, A. P. (1992) J. Cell Sci. 101, 671-679). We have characterized the early stages of receptor down-regulation which occur due to stimulation of receptor internalization from the cell surface. The fact that fluid-phase pinocytosis is also enhanced upon protein kinase C activation indicates that this effect is not specific for the transferrin receptor itself, but is a rather general cellular response to tumor-promoting phorbol esters. The fate of down-regulated transferrin receptors was followed in morphological and subcellular fractionation studies that demonstrate localization of this pool of receptors in early endocytic and recycling compartments. Our results exclude the possibility that transferrin receptor down-regulation results in trafficking of the receptor to lysosomal compartments for degradation. This idea is consistent with the observations that the time course of transferrin receptor degradation is not enhanced in stimulated K562 cells, while transferrin receptor synthesis is shut down. Our results rigorously demonstrate that activation of protein kinase C down regulates the K562 cell transferrin receptor in two stages: acute regulation of early steps in endocytosis that results in an immediate reduction of approximately 40% in cell surface number of receptors and a more chronic reduction in transferrin receptor synthesis upon prolonged exposure to phorbol esters (> 15 h). PMID- 7876110 TI - Lanterns of the firefly Photinus pyralis contain abundant diadenosine 5',5"' P1,P4-tetraphosphate pyrophosphohydrolase activity. AB - The enzyme diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) pyrophosphohydrolase has been purified to homogeneity from firefly lanterns. It is a single polypeptide of M(r) 16,000 with a Km for Ap4A of 1.9 microM and kcat = 3.6 s-1. It is inhibited competitively by adenosine 5'-tetraphosphate (Ki = 7.5 nM) and non-competitively by fluoride ions (Ki = 50 microM). The specific activity of the enzyme in crude extracts of at least 20 milliunits/mg protein is 10-100 times higher than in any other eukaryote so far examined. Interestingly, firefly luciferase is known to synthesize Ap4A and related adenine-containing dinucleoside tetraphosphates in vitro. The high activity of Ap4A hydrolase in lanterns may be related to this ability and could be relevant to the use of the luciferase gene as a reporter gene. PMID- 7876111 TI - Ubiquitin in the prokaryote Anabaena variabilis. AB - The ubiquitin-dependent pathway for protein degradation has been found to play a major role in controlling protein turnover in the cell. Ubiquitin is one of the most conserved proteins yet identified, and up until now it has been thought to be present only in eukaryotes and archaebacteria. This is the first report on the detection and purification of ubiquitin from a eubacterium, the cyanobacterium Anabaena variabilis. The purification procedure included a heat denaturing step, fractionated ammonium sulfate precipitation, two gel filtration runs (Sephadex G 50 and Superose 12), and a final hydroxylapatite chromatography. Comparisons with bovine ubiquitin showed a high similarity with respect to antigenicity to anti ubiquitin (bovine), molecular mass (M(r) = 6,000), isoelectric point (pI 6.5), and NH2-terminal sequence. The existence of ubiquitin in A. variabilis was confirmed by Southern hybridization. In in vitro experiments both cyanobacterial and bovine ubiquitin were covalently attached to several target proteins from A. variabilis, respectively. Data are presented which suggest ubiquitination of dinitrogenase reductase, the Fe-protein subunit of nitrogenase. Our findings imply that ubiquitination equivalent to the eukaryotic system is instrumental in this organism. PMID- 7876112 TI - An amino-terminal variant of the central cannabinoid receptor resulting from alternative splicing. AB - The cDNA sequences encoding the central cannabinoid receptor, CB1, are known for two species, rat and human. However, little information concerning the flanking, noncoding regions is presently available. We have isolated two overlapping clones from a human lung cDNA library with CB1 cDNA inserts. One of these, cann7, contains a short stretch of the CB1 coding region and 4 kilobase pairs (kb) of the 3'-untranslated region (UTR), including two polyadenylation signals. The other, cann6, is identical to cann7 upstream from the first polyadenylation signal, and in addition, it contains the whole coding region and extends for 1.8 kb into the 5'-UTR. Comparison of cann6 with the published sequence (Gerard, C. M., Mollereau, C., Vassart, G., and Parmentier, M. (1991) Biochem. J. 279, 129 134) shows the coding regions to be identical, but reveals important differences in the flanking regions. Notably, the cann6 sequence appears to be that of an immature transcript, containing 1.8 kb of an intronic sequence in the 5'-UTR. In addition, polymerase chain reaction amplification of the CB1 coding region in the IM-9 cell line cDNA resulted in two fragments, one containing the whole CB1 coding region and the second lacking a 167-base pair intron within the sequence encoding the amino-terminal tail of the receptor. This alternatively spliced form would translate to an NH2-terminal modified isoform (CB1A) of the receptor, shorter than CB1 by 61 amino acids. In addition, the first 28 amino acids of the putative truncated receptor are completely different from those of CB1, containing more hydrophobic residues. Rat CB1 mRNA is similarly alternatively spliced. A study of the distribution of the human CB1 and CB1A mRNAs by reverse transcription-polymerase chain reaction analysis showed the presence of both CB1 and CB1A throughout the brain and in all the peripheral tissues examined, with CB1A being present in amounts of up to 20% of CB1. PMID- 7876113 TI - Altered monovinyl and divinyl protochlorophyllide pools in bchJ mutants of Rhodobacter capsulatus. Possible monovinyl substrate discrimination of light independent protochlorophyllide reductase. AB - In land plants in particular, it has been well established that chlorophyll intermediates, Mg-protoporphyrin, Mg-protoporphyrin monomethylester, protochlorophyllide, and chlorophyllide occur as monovinyl and divinyl forms. The pool of monovinyl and divinyl intermediates differ according to species, age of tissue, and light regime. In this study, we investigated the monovinyl and divinyl characteristics of protochlorophyllide and chlorophyllide in the purple non-sulfur photosynthetic eubacterium Rhodobacter capsulatus. Our results indicate that mutations in genes known to completely block the reduction of protochlorophyllide to chlorophyllide (such as bchN, bchB, and bchL mutants), accumulate a pool of monovinyl and divinyl forms of protochlorophyllide just as observed in plants. However, we also observed that directed insertion and deletion mutations in bchJ, a gene located in the photosynthesis gene cluster, affected the ratio of monovinyl and divinyl protochlorophyllide. Specifically, bchJ-disrupted strains accumulate reduced levels of bacteriochlorophyll concomitant with the accumulation of divinyl protochlorophyllide. Mutants of bchJ in combination with a second mutation in bchL still produce a mixed pool of monovinyl and divinyl protochlorophyllide; however, the ratio of monovinyl to divinyl protochlorophyllide is skewed in favor of divinyl protochlorophyllide. These results thus identify bchJ as the first sequenced gene that affects the divinyl to monovinyl ratio of photopigment intermediates in any photosynthetic organism. In addition, the results of our study also suggest that light independent protochlorophyllide reductase is discriminatory for a monovinyl substrate. PMID- 7876114 TI - Enzymic reconstruction of glycosaminoglycan oligosaccharide chains using the transglycosylation reaction of bovine testicular hyaluronidase. AB - The reconstruction of glycosaminoglycan chains using the transglycosylation reaction of testicular hyaluronidase was investigated. First, the optimal conditions for the transglycosylation reaction catalyzed by the enzyme were determined by incubation with the enzyme, using hyaluronic acid (M(r) = 800,000) as a donor and pyridylaminated hyaluronic acid hexasaccharide having glucuronic acid at the nonreducing terminal as an acceptor. The carbohydrate chains as reaction products were determined by high performance liquid chromatography and mass spectrometry. The optimal pH for hydrolysis by the enzyme was found to be about 5.0, whereas that for the transglycosylation reaction was about 7.0. Sodium chloride in the reaction medium inhibited the transglycosylation reaction. Under the optimal conditions, the carbohydrate chains were sequentially transferred along with disaccharide units to the nonreducing terminal of the acceptor and elongated up to docosasaccharide from the acceptor, pyridylaminated hexasaccharide. Using a combination of hyaluronic acid, chondroitin, and chondroitin 4- and 6-sulfate as an acceptor and a donor, it was possible to reconstruct hybrid chains, which were natural or unnatural types of glycosaminoglycan chains. Therefore, it is highly likely that application of the transglycosylation reaction using testicular hyaluronidase would facilitate artificial reconstruction of glycosaminoglycans having some physiological functions. PMID- 7876115 TI - The human tryptophan hydroxylase gene. An unusual splicing complexity in the 5' untranslated region. AB - We report the isolation and the organization of the gene encoding human tryptophan hydroxylase (TPH) and an analysis of the corresponding mRNAs. The gene spans a region of 29 kilobases, which contains at least 11 exons and a variably spliced 5'-untranslated region (5'-UTR). The sequence of the coding region and the majority of the positions of the intron-exon boundaries of human TPH gene are very similar to those encoding human tyrosine hydroxylase and phenylalanine hydroxylase, the other members of the aromatic amino acid hydroxylase family. Phylogenetic analysis evidences the early divergence and the independent evolution of the three hydroxylase types. TPH cDNA cloning and anchored polymerase chain reaction revealed a diversity of the TPH mRNA, which is restricted to the 5'-UTR. Four TPH mRNA species were detected by Northern blot with pineal gland and carcinoid tumor RNAs. These messengers are transcribed from a single transcriptional initiation site, and their diversity results from differential splicing of three intron-like regions and of three exons located in the 5'-UTR. Analysis by S1 nuclease protection revealed that the intron-like regions in the 5'-UTR are mostly unspliced and that TPH mRNA species where the three intron-like regions are eliminated are present at low level in pineal gland and not detectable in carcinoid tumors. PMID- 7876116 TI - Characterization of the human tryptophan hydroxylase gene promoter. Transcriptional regulation by cAMP requires a new motif distinct from the cAMP responsive element. AB - We isolated and sequenced 2,117 nucleotides of the promoter region of the human tryptophan hydroxylase (TPH) gene. Transient transfection in pinealocyte cultures and PC12 cells was used to investigate the human TPH (hTPH) gene promoter activity and its regulation by the cAMP signaling pathway. A region of 2,117 base pairs upstream of the transcription initiation site of the hTPH gene efficiently directed the transcription of a luciferase reporter gene but not in a cell specific manner. The hTPH promoter activity was significantly enhanced by a cyclic AMP analog in the two cell types. Deletion analysis showed that the promoter region from -73 to +2 is sufficient to direct cAMP-dependent transcription, although it does not contain a motif exhibiting a significant identity to the cAMP-responsive element (CRE) or AP-2 binding site. Following site-directed mutagenesis of the region between -73 and -51, an inverted CCAAT box motif was identified as essential for cAMP inducibility of the hTPH promoter. This sequence between -73 and -51 alone allowed cAMP enhancement of transcription when fused to a heterologous promoter. Additionally, electrophoretic mobility shift assays showed that a specific protein-DNA complex is formed between an oligonucleotide corresponding to the inverted CCAAT box motif and nuclear proteins from pinealocytes treated or not treated with cAMP. Thus cAMP responsiveness of hTPH gene expression is mediated by a cis-acting element, which shares strong identity with an inverted CCAAT box and which binds to a constitutively produced nuclear factor. PMID- 7876117 TI - T4 endonuclease V protects the DNA strand opposite a thymine dimer from cleavage by the footprinting reagents DNase I and 1,10-phenanthroline-copper. AB - The glycosylase/abasic lyase T4 endonuclease V initiates the repair of ultraviolet light-induced pyrimidine dimers. This enzyme forms an imino intermediate between its N-terminal alpha-NH2 group and C-1' of the 5'-residue within the dimer. Sodium borohydride was used to covalently trap endonuclease V to a 49-base pair oligodeoxynucleotide containing a site-specific cyclobutane thymine dimer. The bound and free oligonucleotides were then subjected to nuclease protection assays using DNase I and a complex of 1,10-phenanthroline copper. There was a large region of protection from both nucleases produced by endonuclease V evident on the strand opposite and asymmetrically opposed to the dimer. Little protection was seen on the dimer-containing strand. The existence of a footprint with the 1,10-phenanthroline-copper cleavage agent indicated that endonuclease V was interacting with the DNA predominantly via the minor groove. Methylation by dimethyl sulfate yielded no areas of protection when endonuclease V was covalently attached to the DNA, indicating that the protein may closely approach the DNA without direct contact with the bases near the thymine dimer. The Escherichia coli proteins Fpg and photolyase display a very different pattern of nuclease protection on their respective substrates, implying that endonuclease V recognizes pyrimidine dimers by a novel mechanism. PMID- 7876118 TI - Specific nicking-closing activity of the initiator of replication protein RepB of plasmid pMV158 on supercoiled or single-stranded DNA. AB - Asymmetric rolling circle replication of the promiscuous replicon pMV158 is initiated by the plasmid-encoded RepB protein. In vitro, purified RepB protein introduces a nick within the leading strand origin of replication by a nucleophylic attack on the phosphodiester bond at the dinucleotide GpA. Some changes within and around this dinucleotide were recognized by the protein. RepB nicked and closed supercoiled pMV158 DNA, having an optimum activity at 60 degrees C. We have imitated, in vitro, a process of rolling circle replication, since RepB was able to nick (initiation) and to covalently close (termination) single-stranded oligonucleotides containing the protein cleavage sequence. Covalent DNA-protein complexes were not found, indicating that RepB has unique features among plasmid-encoded proteins involved in rolling-circle replication or conjugative mobilization. PMID- 7876119 TI - Identification and characterization of carboxyl ester hydrolase as a phospholipid hydrolyzing enzyme of zymogen granule membranes from rat exocrine pancreas. AB - Salt-washed (0.6 m NaCl) zymogen granule membranes (ZGM) of rat pancreatic acinar cells were utilized to identify and characterize membrane protein(s) responsible for phospholipase and lysophospholipase activities. Five major bands were identified in salt-washed ZGM by Coomassie Brilliant Blue. A 70-kDa protein with enzymatic activity was retained in significant quantities after several washes with 0.6 M NaCl but could be displaced from ZGM by 2 m NaCl or by 100 mg/ml heparin. By contrast, GP2, an integral membrane protein, was not displaced under these conditions. These findings suggest that the enzyme is a peripheral membrane protein of ZGM. Renaturation of ZGM proteins following electrophoresis revealed that the 70-kDa protein possessed phospholipase activity. Identification of the 70-kDa protein as a membrane-associated carboxyl ester hydrolase was based upon: (a) the use of a specific polyclonal antiserum, (b) N-terminal sequence, (c) two dimensional gel analysis, (d) enzymatic characterization, and (e) co-localization to an area of a non-reducing gel containing significant phospholipase activity. Other ZGM proteins, namely GP2 and GP3, could not be demonstrated to possess phospholipase activity under the experimental conditions employed. Our finding that carboxyl ester hydrolase from ZGM exhibits PLA1 and lysophospholipase activities represents the first identification and characterization of a protein responsible for phospholipase activity in secretory granule membranes. PMID- 7876120 TI - Mitochondrial import of subunit Va of cytochrome c oxidase characterized with yeast mutants. AB - We have investigated the unusual import pathway of cytochrome c oxidase subunit Va (COXVa) into the yeast mitochondrial inner membrane by use of mutants that lack import receptors or are defective in matrix hsp70. (i) Mitochondria lacking the receptor MOM72 are not impaired in import of COXVa. Mitochondria lacking the main receptor MOM19 are moderately reduced in import of COXVa; this, however, is caused by a reduction of the inner membrane potential and not by a lack of specific receptor functions. (ii) Mitochondria defective in the unfoldase function of matrix hsp70 efficiently import COXVa, whereas mitochondria defective in the translocase function of the hsp70 are blocked in import of COXVA. A COXVa construct where the internal hydrophobic sorting signal is placed close to the presequence does not require either hsp70 function. These results demonstrate that import of COXVa does not require MOM19 or MOM72, but they unexpectedly reveal a strong dependence on the translocase function of matrix hsp70. Two important implications about the characterization of mitochondrial protein import in general are obtained. First, the interpretation of import results with mutants lacking MOM19 have to consider effects on the membrane potential. Second, the distance between a matrix targeting sequence and a hydrophobic sorting sequence within a precursor appears to determine if the inner membrane sorting machinery can substitute for the translocase function of hsp70 or not. PMID- 7876121 TI - The purification and characterization of a human dual-specific protein tyrosine phosphatase. AB - An expression and purification method was developed to obtain the recombinant human dual-specific protein tyrosine phosphatase (PTPase) VHR in quantities suitable for both kinetic studies and crystallization. Physical characterization of the homogeneous recombinant protein verified the mass to be 20,500 +/- 100 by matrix-assisted laser desorption mass spectrometry, confirmed the anticipated NH2 terminal amino acid sequence and demonstrated that the protein exists as a monomer. Conditions were developed to obtain crystals which were suitable for x ray structure determination. Using synthetic diphosphorylated peptides corresponding to MAP177-189 (mitogen-activated protein) kinase (DHTG FLpTEpYVATR), an assay was devised which permitted the determination of the rate constants for dephosphorylation of the diphosphorylated peptide on threonine and tyrosine residues. The diphosphorylated peptides are preferred over the singly phosphorylated on tyrosine by 3-8-fold. The apparent second-order rate constant kcat/Km for dephosphorylation of phosphotyrosine on DHTGFLpTEpYVATR was 32,000 M 1 S-1 while dephosphorylation of phosphothreonine was 14 M-1 S-1 (pH 6). The reaction of DHTGFLpTEpYVATR with VHR is ordered, with rapid dephosphorylation on tyrosine occurring first followed by slow dephosphorylation on threonine. Similar results were obtained with F(NLe)(N-Le)pTPpYVVTR, a peptide corresponding to a MAP kinase-like protein (JNK1(180-189)) which is involved in the stress response signaling pathway. PMID- 7876122 TI - Stage-dependent and temperature-controlled expression of the gene encoding the precursor protein of diapause hormone and pheromone biosynthesis activating neuropeptide in the silkworm, Bombyx mori. AB - Embryonic diapause and sex pheromone biosynthesis in the silkworm, Bombyx mori, are, respectively, induced by diapause hormone (DH) and pheromone biosynthesis activating neuropeptide (PBAN), which are produced in the subesophageal ganglion from a common polyprotein precursor (DH-PBAN precursor) encoded by a single gene (DH-PBAN gene). Using DH-PBAN cDNA as a probe, we quantitatively measured DH-PBAN mRNA content throughout embryonic and postembryonic development and observed the effects of incubation temperature, which is a key factor for determination of diapause, on DH-PBAN gene expression. The silkworm, which is programmed to lay diapause eggs by being incubated at 25 degrees C, showed peaks of DH-PBAN mRNA content at five different stages throughout the life cycle: at the late embryonic stage, at the middle of the fourth and the fifth larval instars, and at early and late stages of pupal-adult development. In the non-diapause type silkworms programmed by a 15 degrees C incubation, only the last peak of DH-PBAN mRNA in pupal-adult development was found, and the other peaks were absent. Furthermore, interruption of the incubation period at 25 degrees C by incubation at 15 degrees C decreased both DH-PBAN mRNA content in mature embryos and in subesophageal ganglia of day 3 pupae and the incidence of diapause eggs. Thus, there were two types of regulatory mechanisms for DH-PBAN gene expression. One is a temperature controlled expression that is responsible for diapause induction, and the other is a temperature-independent, stage-dependent expression related to pheromone production. PMID- 7876123 TI - Fluorescence resolution of the intrinsic tryptophan residues of bovine protein tyrosyl phosphatase. AB - Fluorescence steady-state and lifetime measurements have been performed that permit the differentiation of the 2 intrinsic tryptophan residues in bovine low molecular weight phosphotyrosyl protein phosphatase (BPTP). Spectral information was obtained by use of two single-tryptophan mutant proteins, W39F and W49F, and the double mutant protein W39,49F. Fluorescence measurements show that Trp39 is characterized by a large blue shift, a low quantum yield, and a shorter mean lifetime compared to Trp49. Solute fluorescence quenching studies of W39F reveal that Trp49 is highly exposed to the aqueous environment. In contrast, Trp39 is situated within a hydrophobic core and is only partially accessible to quenching agents such as acrylamide, iodide ion, and cesium ion. The fluorescence contributions of Trp39 and Trp49 are additive, and their sum is equivalent to that observed for wild type BPTP. Calculated intramolecular distances between Trp39 or Trp49 and a 5-[[(acetylamino)-ethyl]amino]naphthalene-1- sulfonate group covalently bound at Cys12 or Cys17 of the respective protein mutants, place Trp49 within 10 A and Trp39 at least 20 A from the active site. The fluorescence decay of the single tryptophan mutants and, surprisingly, wild type BPTP were each adequately fitted as biexponentials. The latter is a consequence of the imprecision involved in determining actual minima in a three- and four exponential fitting. Comparison of quenching results of wild type BPTP with those of the single tryptophan mutant proteins indicates that minor fluorescence components, easily resolved using a biexponential fitting for the mutant proteins, are unresolvable for wild type BPTP. These minor components skewed the weighted magnitudes and induced perturbations in lifetimes for the tryptophan fluorescence of wild type BPTP, which directly influenced the calculated values of Ksv and kq. PMID- 7876124 TI - MH1, a second-site revertant of an Escherichia coli mutant lacking Na+/H+ antiporters (delta nhaA delta nhaB), regains Na+ resistance and a capacity to excrete Na+ in a delta microH(+)-independent fashion. AB - The Escherichia coli mutant delta nhaA delta nhaB (EP432), which lacks the two specific Na+/H+ antiporter genes, is incapable of efficiently excreting Na+. Accordingly at low K+ (6 mM) medium, its intracellular Na+ concentration is only slightly lower (1.5-2x) than the extracellular concentration (50 mM), explaining the high sensitivity to Na+ (> or = 30 mM) of the mutant. This Na+ sensitivity is shown to be a powerful selection for spontaneous second-site suppressor mutations that allow growth on high Na+ (< or = 0.6 M) with a rate similar to that of the wild type. One such mutation, MH1, maps at 25.7 min on the E. coli chromosome. It confers Na+ but not Li+ resistance upon delta nhaA delta nhaB cells and exposes a Na(+)-excreting capacity, maintaining a Na+ gradient of about 8-10 (at 50 mM extracellular Na+), which is similar to that of the wild type. Although lower, Na+ excretion capacity is also observed in the delta nhaA delta nhaB mutant when grown in medium containing higher K+ (70 mM). This capacity is accompanied with a shift in the sensitivity of the mutant to higher Na+ concentrations (> or = 300 mM). Whereas Na+ excretion by a wild type carrying delta unc is uncoupler sensitive, that of MH1 delta unc is dependent on respiration in an uncoupler insensitive fashion. It is concluded that under some conditions (high K+ in the medium or in MH1-like mutants), a primary pump driven by respiration is responsible for Na+ extrusion when the Na+/H+ antiporters are not active. PMID- 7876125 TI - Veratryl alcohol oxidase from Pleurotus ostreatus participates in lignin biodegradation and prevents polymerization of laccase-oxidized substrates. AB - Oxidative enzymes (laccases and peroxidases) isolated from the culture media of different fungi are involved in the basic mechanism of ligninolysis via radical intermediates. However, experiments aimed at reproducing natural biodegradation in vitro have been unsuccessful so far since the single biocatalysts alone are not able to solubilize lignins because of the simultaneous recondensation of these intermediates. FAD oxidases can prevent this side reaction in lignin depolymerization by reducing quinonoids and radical compounds. This study investigates the possible role of a laccase and a FAD-dependent aryl alcohol oxidase (veratryl alcohol oxidase, VAO) excreted by the basidiomycete Pleurotus ostreatus. In fact, we found that VAO is able to reduce synthetic quinones, laccase-generated quinonoids, and phenoxy radicals with concomitant oxidation of veratryl alcohol to veratryl aldehyde. This cooperative action of laccase and VAO also prevented the polymerization of phenolic compounds and reduced the molecular weight of soluble lignosulfonates to a significant extent. PMID- 7876127 TI - The human peroxisome proliferator-activated receptor (PPAR) subtype NUC1 represses the activation of hPPAR alpha and thyroid hormone receptors. AB - We have cloned two human peroxisome proliferator-activated receptor (PPAR) subtypes, hPPAR alpha and hNUC1. hPPAR alpha is activated by clofibric acid and other PPAR activators. hNUC1 is not activated by these compounds acting instead as a repressor of hPPAR alpha and human thyroid hormone receptor transcriptional activation. Repression is specific since hNUC1 does not significantly repress activation by the progesterone or retinoic acid receptors. We demonstrate co operative binding of hNUC1 and hRXR alpha to a PPAR-responsive element and show that in the presence of hRXR alpha, the affinity of hNUC1 for the peroxisome proliferator is comparable to that of hPPAR alpha. Furthermore, repression of hPPAR alpha can be overcome by transfecting excess hPPAR alpha. We propose that hNUC1 represses the activity of hPPAR alpha by titrating out a factor required for activation. Our data further suggests convergence of thyroid hormone- and peroxisome-mediated fatty acid metabolism pathways. Overcoming hNUC1 repression could be a means of increasing the activity of these receptors. PMID- 7876126 TI - A chimeric bacterial phosphofructokinase exhibits cooperativity in the absence of heterotropic regulation. AB - The phosphofructokinases (PFKs) from the bacteria Escherichia coli and Bacillus stearothermophilus differ markedly in their regulation by ATP. Whereas E. coli PFK (EcPFK) is profoundly inhibited by ATP, B. stearothermophilus PFK (BsPFK) is only slightly inhibited. The structural basis for this difference could be closure of the active site via a conformational transition that occurs in the ATP binding domain of EcPFK, but is absent in BsPFK. To investigate the role of this transition in ATP inhibition of EcPFK, we have constructed a chimeric enzyme that contains the "rigid" ATP-binding domain of BsPFK grafted onto the remainder of the EcPFK subunit. The chimeric PFK has the following characteristics: (i) tetrameric structure and kinetic parameters similar to those of the native enzymes, (ii) insensitivity to regulation by the effector phosphoenolpyruvate despite its ability to bind to the enzyme, and (iii) a sigmoidal (nH around 2) fructose 6-phosphate saturation curve. From the results, it is concluded that the active site regions of the two native enzymes are remarkably similar, but their effector sites and their mechanisms of heterotropic regulation are different. The chimeric subunit is locked in a structure resembling that of activated E. coli PFK, yet the enzyme can exist in two different conformational states. Mechanisms for its sigmoidal kinetics are discussed. PMID- 7876128 TI - Molecular cloning and characterization of bovine beta-mannosidase. AB - Deficiency of lysosomal beta-mannosidase activity results in a severe neurodegenerative disease in goats and cattle and a relatively milder phenotype in humans. A cDNA coding for the entire beta-mannosidase protein is described. Mixed oligonucleotides derived from bovine beta-mannosidase peptide sequences were used to screen a bovine thyroid cDNA library. Clones covering about 80% of the C-terminal region were recovered. The missing 5'-region was obtained using the technique of 5'-rapid amplification of cDNA ends. The composite cDNA contains 3852 nucleotides, encoding 879 amino acids. The N-terminal methionine is followed by 16 amino acids displaying the characteristics of a typical signal peptide sequence. The deduced amino acid sequence is colinear with all peptide sequences determined by protein microsequencing. Northern blot analysis demonstrates a single 4.2-kilobase transcript in various tissues from both normal and affected goats and calves. The mRNA level is decreased in tissues of affected beta mannosidosis animals. The gene encoding beta-mannosidase is localized to human chromosome 4 as shown by Southern analysis of rodent/human somatic cell hybrids. This is the first report of cloning of lysosomal beta-mannosidase. PMID- 7876130 TI - Construction of an SH2 domain-binding site with mixed specificity. AB - SH2 domains bind to specific phosphotyrosine-containing sites in a fashion dictated by the amino acids flanking the phosphotyrosine. Attention has focused on the role of the three COOH-terminal positions (+1 to +3) in generating specificity. Autophosphorylation of Tyr1021 in the tail of the beta-receptor for platelet-derived growth factor creates a specific binding site for the COOH terminal SH2 domain of phospholipase C (PLC)-gamma 1. We show that the residues 4 and 5 amino acids COOH-terminal to Tyr1021 (+4 Leu and +5 Pro) are required for efficient PLC-gamma 1 binding, and that their replacement with the corresponding residues from a phosphatidylinositol 3'-kinase binding site abrogates stable association with PLC-gamma 1. In contrast, replacement of the +3 Pro with Met produces a Tyr1021 site with mixed specificity that binds both PLC-gamma 1 and phosphatidylinositol 3'-kinase. This motif is rendered specific for phosphatidylinositol 3'-kinase by further substitution of the +4 Leu. These results indicate that the +4 and +5 residues are important for the selective binding of specific SH2 domains. This study suggests that phosphotyrosine sites can be tailored to bind one or more SH2 domains with high affinity, depending on the combination of residues in the +1 to +5 positions. PMID- 7876129 TI - Regulation of the tissue factor promoter in endothelial cells. Binding of NF kappa B-, AP-1-, and Sp1-like transcription factors. AB - Tissue factor is up-regulated on endothelial cells and monocytes in response to cytokines and endotoxin and is the main trigger of the extrinsic pathway of the coagulation cascade. We have isolated the porcine tissue factor gene and studied the regulation of the promoter, which has not been investigated previously in endothelial cells. Comparison of the promoter sequences with the respective human and murine genes reveals short stretches of homology, which encompass potential binding sites for AP-1, NF kappa B, and Sp1 transcription factors. Using DNase I footprinting, we detect binding of nuclear factors to these promoter elements. Transfection experiments demonstrate that a 300-base pair fragment containing the conserved elements can mediate induced transcription and that the NF kappa B-like element is essential. In accordance, electrophoretic mobility shift assays show a strong increase in the binding of factors to the NF kappa B-like site following induction. We further provide evidence that RelA (p65), c-Rel, and possibly novel polypeptides bind to the tissue factor NF kappa B element. In addition, we show constitutive binding of members of the Fos/Jun and Sp1 families to the AP-1 and Sp1 sites, respectively. We propose a concerted action of AP-1-, NF kappa B-, and Sp1-like factors in transcription from the tissue factor promoter in endothelial cells. PMID- 7876131 TI - Identification of two regulatory elements within the promoter region of the mouse connexin 43 gene. AB - To define the minimal sequences required for expression of the connexin 43 gene (cx43) in myometrial cells, we generated 5' deletion constructs of a fragment extending 1686 base pairs upstream and 162 base pairs downstream of the transcription start site and determined their ability to drive expression of the chloramphenicol acetyltransferase reporter gene in transfected myometrial cell lines. Our investigation revealed two cis-acting regulatory elements within this fragment. Deletion of a region extending from -102 to -92 led to an increase of the promoter activity by greater than 10-fold, indicating a presence of a repressor element. Deletion of a region extending from -72 to -62 caused a decrease of the promoter activity of a similar extent, implying the existence of a positive element. Electrophoretic mobility shift assays demonstrated that synthetic oligonucleotides derived from these two small regions can each bind with a nuclear protein(s) prepared from myometrial cells, and an introduction of three and two base substitutions into each of these oligomers was sufficient to abolish their protein binding capability. These same mutations, when incorporated in the chloramphenicol acetyltransferase constructs, diminished regulatory functions of the negative and positive elements, and the protein(s) that bind to these functional elements was found in several tissues known to express cx43 gene. PMID- 7876132 TI - Sequence, genomic organization, and expression of the novel homeobox gene Hesx1. AB - Extensive analyses of homeobox gene expression and function during murine embryogenesis have demonstrated that homeobox gene products are key components in the establishment of pattern formation and regional identity during development. In this paper we report the molecular characterization and expression of a novel murine homeobox sequence, Hesx1, isolated from pluripotent embryonic stem cells. Hesx1 is expressed as two transcripts of 1.0 and 1.2 kilobases which encode an identical 185 amino acid open reading frame. The transcripts differ in the 3' untranslated region due to the differential utilization of a weak splice donor site located immediately downstream of the translation termination codon. The Hesx1 homeodomain shared 80% identity with the Xenopus homeoprotein XANF-1 and was less than 50% related to other homeodomain sequences. Hesx1 and XANF-1 therefore constitute the founder members of a new homeodomain class. Hesx1 expression was down-regulated during embryonic stem cell differentiation and was detected in tissue-specific RNA samples derived from the embryonic liver, and at lower levels in viscera, amnion, and yolk sac. Expression in adult mice was not detected. These sites of expression are consistent with a role for Hesx1 in the regulation of developmental decisions in the early mouse embryo and during fetal hematopoiesis. PMID- 7876133 TI - Functional domains of the ferredoxin transit sequence involved in chloroplast import. AB - In order to analyze the information content of a chloroplast transit sequence, we have constructed and analyzed by in vitro assays seven substitution and 20 deletion mutants of the ferredoxin transit sequence. The N-terminal part and the C-terminal part are important for targeting, and in addition the C-terminal region is required for processing. A third region is important for translocation but not for the initial interaction with the envelope. A fourth region is less essential for in vitro import. Purified precursors were tested for their ability to compete for the in vitro import of radiolabeled wild-type precursor, which confirmed the important role in chloroplast recognition of both the N- and the C terminal domain of the transit sequence. Monolayer experiments showed that the N terminus was mainly involved in the insertion into mono-galactolipid-containing lipid surfaces whereas the C terminus mediates the recognition of negatively charged lipids. A sequence comparison to other transit sequences suggests that the domain structure of the ferredoxin transit sequence can be extended to these sequences and thus reveals a general structural design of transit sequences. PMID- 7876134 TI - AFAP-120. A variant form of the Src SH2/SH3-binding partner AFAP-110 is detected in brain and contains a novel internal sequence which binds to a 67-kDa protein. AB - SH2 and SH3 domains have been characterized as functional domains that mediate protein-protein interactions in signal transduction. Recently, the cDNA sequence of a novel Src- and Fyn-binding protein called AFAP-110, for Actin-Filament Associated Protein-110 kDa, was reported. This protein was distinctive in that it is both an SH2 and SH3 binding partner for the non-receptor tyrosine kinases Src and Fyn. Here, we report the characterization of an alternatively processed form of AFAP-110 that encodes an additional 258 base pair (bp) of open reading frame. Transient expression of this full-length clone reveals a molecular mass of 120 kDa. Western blot analysis indicate that a larger 120-kDa variant of AFAP-110 can be detected in brain and is not detectable in any other tissues examined. Northern blot analysis indicate that the novel 258-bp insert can be detected in brain RNA but not chick embryo fibroblast RNA. We propose the name AFAP-120, for Actin Filament-Associated Protein-120 kDa. Expression of the 258-bp novel insert (NINS) as a glutathione S-transferase-encoded fusion protein permits adsorption of a 67-kDa protein from tissue lysates. Deletion analysis of the NINS indicates that the interaction with p67 can be attributed to a proline-rich motif that resembles an SH3-binding motif. We hypothesize that AFAP-120 facilitates interactions in brain between SH2/SH3 signaling proteins and actin filaments and that a proline-rich motif in the NINS may exist to facilitate additional interactions between cellular proteins in brain and actin filaments. PMID- 7876135 TI - Cloning of a cDNA for liver microsomal retinol dehydrogenase. A tissue-specific, short-chain alcohol dehydrogenase. AB - Retinoic acid, a hormone biosynthesized from retinol, controls numerous biological systems by regulating eukaryotic gene expression from conception through death. This work reports the cloning and expression of a liver cDNA encoding a microsomal retinol dehydrogenase (RoDH), which catalyzes the primary and rate-limiting step in retinoic acid synthesis. The predicted amino acid sequence and biochemical data obtained from the recombinant enzyme verify it as a short-chain alcohol dehydrogenase. Like microsomal RoDH, the recombinant enzyme recognized as substrate retinol bound to cellular retinol-binding protein, had higher activity with NADP rather than NAD, was stimulated by ethanol or phosphatidylcholine, was not inhibited by 4-methylpyrazole, was inhibited by phenylarsine oxide and carbenoxolone and localized to microsomes. RoDH recognized the physiological form of retinol, holocellular retinol-binding protein, with a Km of 0.9 microM, a value lower than the approximately 5 microM concentration of holocellular retinol binding protein in liver. Northern and Western blot analyses revealed RoDH expression only in rat liver, despite enzymatic activity in liver, brain, kidney, lung, and testes. These data suggest that tissue-specific isozyme(s) of short chain alcohol dehydrogenases catalyze the first step in retinoic acid biogenesis and further strengthen the evidence that the "cassette" of retinol bound to cellular retinol-binding protein serves as a physiological substrate. PMID- 7876136 TI - Active site mapping of the catalytic mouse primase subunit by alanine scanning mutagenesis. AB - In the eukaryotic cell, DNA synthesis is initiated by DNA primase associated with DNA polymerase alpha. The eukaryotic primase is composed of two subunits, p49 and p58, where the p49 subunit contains the catalytic active site. Mutagenesis of the cDNA for the p49 subunit was initiated to demonstrate a functional correlation of conserved residues among the eukaryotic primases and DNA polymerases. Fourteen invariant charged residues in the smaller catalytic mouse primase subunit, p49, were changed to alanine. These mutant proteins were expressed, purified, and enzymatically characterized for primer synthesis. Analyses of the mutant proteins indicate that residues 104-111 are most critical for primer synthesis and form part of the active site. Alanine substitution in residues Glu105, Asp109, and Asp111 produced protein with no detectable activity in direct primase assays, indicating that these residues may form part of a conserved carboxylic triad also observed in the active sites of DNA polymerases and reverse transcriptases. All other mutant proteins showed a dramatic decrease in catalysis, while mutation of two residues, Arg162 and Arg163, caused an increase in Km(NTP). Analysis of these mutant proteins in specific assays designed to separately investigate dinucleotide formation (initiation) and elongation of primer indicates that these two activities utilize the same active site within the p49 subunit. Finally, mutations in three active site codons produced protein with reduced affinity with the p58 subunit, suggesting that p58 may interact directly with active site residues. PMID- 7876137 TI - Expression of PG-M(V3), an alternatively spliced form of PG-M without a chondroitin sulfate attachment in region in mouse and human tissues. AB - We showed previously that the alternative splicing of chondroitin sulfate attachment domains (CS alpha and CS beta) yielded multiforms of the PG-M core protein in mouse. A transcript encoding a new short form of the core protein PG M(V3) was found in various mouse tissues using polymerase chain reaction. DNA sequences of the polymerase chain reaction products suggested that PG-M(V3) had no chondroitin sulfate attachment domain. PG-M(V3) was also detected in various human tissues. The presence of a transcript for PG-M(V3) was further supported by Northern blot analysis. Southern blot analysis confirmed that multiforms of the PG-M core protein, including PG-M(V3), were derived from a single genomic locus by an alternative splicing mechanism. Because PG-M(V3) has no chondroitin sulfate attachment region, which is the most distinctive portion of a proteoglycan molecule, this form may have a unique function. PMID- 7876138 TI - Effect of caldesmon on the assembly of smooth muscle myosin. AB - Smooth muscle myosin filaments are much less stable than the skeletal muscle counterpart. Smooth myosin requires higher concentration of Mg2+ than skeletal myosin to form thick filaments and addition of ATP disassembles the dephosphorylated smooth muscle myosin filaments into monomers but not phosphorylated ones. We found that the addition of caldesmon to dephosphorylated myosin induced the formation of the filaments under the conditions where myosin by itself is soluble or disassembled. Although the induced filaments were short at 1 mM Mg2+, they became medium sized and seemed like side polar filaments with prominent 14 nm periodicity at higher Mg2+ conditions (8 mM). In the presence of F-actin, myosin filaments induced by caldesmon were associated along actin filaments to form large structures. The association of actin and myosin filaments was observed only in the presence of caldesmon, suggesting that caldesmon cross linked actin and myosin filaments. This cross-linking was disrupted by the addition of calmodulin. Caldesmon-induced filament formation of dephosphorylated myosin in the presence of Mg(2+)-ATP may explain the existence of myosin filaments in relaxed smooth muscle fibers. A similar effect of telokin on myosin filament assembly was also examined and is discussed. PMID- 7876139 TI - Subunit interactions in dimeric kinesin heavy chain derivatives that lack the kinesin rod. AB - The N-terminal residues of the two heavy chains of the motor enzyme kinesin form two globular "heads"; the heads are attached to a "rod" domain which is a two stranded alpha-helical coiled-coil. Interaction between the heads is thought to be important to kinesin function. The rod may not be necessary for head-head interactions because a heavy chain N-terminal fragment containing only residues from the head and adjacent region forms dimers (Huang, T.-G., Suhan, J., and Hackney, D. D. (1994) J. Biol. Chem. 269, 16502-16507). However, the nature and stability of the subunit-subunit interactions in such derivatives are unclear. To examine the physical properties of heavy chain interaction in and near the head domains, we characterized the self-association behavior of two dimeric kinesin derivatives predicted (Lupas, A., van Dyke, M., and Stock, J. (1991) Science 252, 1162-1164) to lack the rod. Derivative K448-BIO contains the 448 N-terminal residues of Drosophila kinesin heavy chain fused at the C terminus to a 2-residue linker and a C-terminal fragment from Escherichia coli biotin carboxyl carrier protein; derivative K448-L is the same except that it lacks the biotin carboxyl carrier protein fragment. Both derivatives expressed in insect cells display microtubule-stimulated ATPase activity; K448-BIO also displays microtubule motility. Equilibrium sedimentation and gel filtration indicate that purified K448-BIO and K448-L at 0.02-0.4 mg/ml form homogeneous solutions of homodimers with no detectable formation of monomers or higher order oligomers. Derivative self-association is non-covalent but extremely stable with an association constant > or = 2 x 10(8) M-1. Stable subunit-subunit association induced by structures in and near the kinesin heads may be necessary for full mechanochemical function. PMID- 7876141 TI - Calnexin recognizes carbohydrate and protein determinants of class I major histocompatibility complex molecules. AB - Proper folding of nascent polypeptides is essential for their function and is monitored by intracellular "quality control" elements. The molecular chaperone calnexin participates in this process by retaining in the endoplasmic reticulum a variety of unfolded proteins, including class I major histocompatibility complex molecules. We transfected human B cell lines with genes encoding either wild-type HLA-A2 heavy chains or mutant heavy chains lacking sites for glycosylation or deficient in binding to beta 2-microglobulin (beta 2m). In CIR cells, calnexin did not associate detectably with wild-type heavy chains but bound strongly to mutant heavy chains unable to bind beta 2m. Removal of the glycosylation addition site by further mutagenesis prevented binding of mutant heavy chains to calnexin. In Daudi cells, deficient in synthesis of beta 2m, wild-type HLA-A2 heavy chains, but not a non-glycosylated mutant, bound calnexin. Castanospermine, which blocks trimming of glucose residues from asparagine-linked glycans, inhibited association of calnexin with heavy chains encoded by a second class I gene, HLA B*0702. Although initiation of calnexin binding appears to depend on the presence of oligosaccharide on the substrate, removal of the glycan from calnexin associated heavy chains by digestion with endoglycosidase H did not disrupt the interaction. These results suggest that calnexin first recognizes carbohydrate on substrate proteins and then binds more stably to peptide determinants, which disappear upon folding. PMID- 7876140 TI - Okadaic acid stimulates glucose transport in rat adipocytes by increasing the externalization rate constant of GLUT4 recycling. AB - GLUT4, the major insulin-responsive glucose transporter isoform in rat adipocytes, rapidly recycles between the cell surface and an intracellular pool with two first order rate constants, one for internalization (kin) and the other for externalization (kex). Insulin decreases kin by 2.8-fold and increases kex by 3.3-fold, thus increasing the steady-state cell surface GLUT4 level by approximately 8-fold (Jhun, B. H., Rampal, A. L., Liu, H., Lachaal, M., and Jung, C. (1992) J. Biol. Chem. 267, 17710-17715). To gain an insight into the biochemical mechanisms that modulate these rate constants, we studied the effects upon them of okadaic acid (OKA), a phosphatase inhibitor that exerts a insulin like effect on glucose transport in adipocytes. OKA stimulated 3-O-methylglucose transport maximally 3.1-fold and increased the cell surface GLUT4 level 3.4-fold. When adipocytes were pulse-labeled with an impermeant, covalently reactive glucose analog, [3H]1,3-bis-(3-deoxy-D-glucopyranose-3-yloxy)-2-propyl 4 benzoylbenzoate, and the time course of labeled GLUT4 recycling was followed, the kex was found to increase 2.8-fold upon maximal stimulation by OKA, whereas the kin remained unchanged within experimental error. These findings demonstrate that OKA mimics the insulin effect on only GLUT4 externalization and suggest that insulin stimulates GLUT4 externalization by increasing the phosphorylation state of a serine/threonine phosphoprotein, probably by inhibiting protein phosphatase 1 or 2A. PMID- 7876142 TI - Variations in transcription-repair coupling in mouse cells. AB - Formation and repair of UV-induced cyclobutane pyrimidine dimers (CPDs) was examined in three different genes in mouse L cells: 1) a stably integrated insert (called LTL), consisting of a herpes simplex virus thymidine kinase gene (tk) fused to a hormone inducible promotor (LTR); 2) the constitutively expressed proto-oncogene c-abl; and 3) the inactive immunoglobulin J chain gene. Transcription of the tk gene is induced > 50-fold by dexamethasone. There is a nonuniform distribution of CPDs in LTL DNA irradiated in vitro, being 4-fold higher in the LTR than in the tk gene, indicating the LTR may be damaged preferentially in irradiated cells. Repair of CPDs occurs efficiently in both strands of LTL and is unaffected by hormone induction of tk gene transcription. Transcription of tk mRNA is very sensitive to UV damage and follows single hit kinetics with UV dose. Furthermore, tk mRNA expression rapidly recovers during repair incubation. Transcription-coupled repair occurs in these cells, however, since only the transcribed strand of c-abl is efficiently repaired of CPDs; the non-transcribed strand as well as both strands of the J chain gene are inefficiently repaired. Thus, repair in the LTL construct may reflect a lack of transcription-coupled repair in either the LTR promotor or the LTL insertion region of chromatin. PMID- 7876143 TI - Interferon gamma receptor extracellular domain expressed as IgG fusion protein in Chinese hamster ovary cells. Purification, biochemical characterization, and stoichiometry of binding. AB - Agents that antagonize the functions of interferon gamma (IFN gamma) are potential pharmaceuticals against several immunological and inflammatory disorders. IFN gamma receptor-immunoglobulin G fusion proteins (IFN gamma R-IgG) function as antagonists of endogenous IFN gamma and have longer half-lives in vivo in comparison with soluble IFN gamma receptors (sIFN gamma R), consisting of the extracellular region of the native sequence. A fusion protein comprising the extracellular domain of the human IFN gamma receptor and the hinge, CH2 and CH3 domains of the human IgG3 constant region, was expressed in Chinese hamster ovary cells. The IFN gamma R-IgG3 fusion protein was secreted into the culture medium as a 175-kDa glycoprotein and was purified over Protein G-Sepharose, DEAE Sepharose, and size exclusion chromatography. IFN gamma R-IgG3 bound IFN gamma in solid phase assays and ligand blots, competed for the binding of radiolabeled IFN gamma to the cell surface receptor of Raji cells, and inhibited the IFN gamma mediated antiviral activity with an efficiency at least one order of magnitude higher than that of the soluble receptor produced in the same expression system. Two IFN gamma R-IgG3 fusion proteins bound two IFN gamma dimers forming a complex of approximately 380 kDa. In immunodiffusion assays, the IFN gamma R-IgG3 fusion protein did not precipitate IFN gamma. Dissociation of bound IFN gamma from IFN gamma R-IgG3 was 2-fold slower than from the sIFN gamma R produced in insect cells. PMID- 7876144 TI - Activation of acute phase response factor (APRF)/Stat3 transcription factor by growth hormone. AB - The mechanism by which the binding of growth hormone (GH) to its cell surface receptor elicits changes in gene transcription are largely unknown. The transcription factor Stat1/p91 has been shown to be activated by GH. Here we show that acute phase response factor or Stat3 f1p4an antigenically related protein), is also activated by GH. Stat3 has been implicated in the interleukin-6-dependent induction of acute phase response genes. GH promotes in 3T3-F442A fibroblasts the tyrosyl phosphorylation of a protein immunoprecipitated by antibodies to Stat3. This protein co-migrates with a tyrosyl phosphorylated protein from cells treated with leukemia inhibitory factor, a cytokine known to activate Stat3. Tyrosyl phosphorylated Stat3 is also observed in response to interferon-gamma. Stat3 is present in GH-inducible DNA-binding complexes that bind the sis-inducible element in the c-fos promoter and the acute phase response element in the alpha 2 macroglobulin promoter. The ability of GH to activate both Stat1 and Stat3 (i.e. increase their tyrosyl phosphorylation and ability to bind to DNA) suggests that gene regulation by GH involves multiple Stat proteins. Shared transcription factors among hormones and cytokines that activate JAK kinases provide an explanation for shared responses, while the ability of the different ligands to differentially recruit various Stat family members suggests mechanisms by which specificity in gene regulation could be achieved. PMID- 7876145 TI - Stimulation of phospholipase D by epidermal growth factor requires protein kinase C activation in Swiss 3T3 cells. AB - The proposal that epidermal growth factor (EGF) activates phospholipase D (PLD) by a mechanism(s) not involving phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) hydrolysis was examined in Swiss 3T3 fibroblasts. EGF, basic fibroblast growth factor (bFGF), bombesin, and platelet-derived growth factor (PDGF) activated PLD as measured by transphosphatidylation of butanol to phosphatidylbutanol. The increase in inositol phosphates induced by bFGF, EGF, or bombesin was significantly enhanced by Ro-31-8220, an inhibitor of protein kinase C (PKC), suggesting that PtdIns(4,5)P2-hydrolyzing phospholipase is coupled to the receptors for these agonists but that the response is down-regulated by PKC. Activation of PLD by EGF was inhibited dose dependently by the PKC inhibitors bis indolylmaleimide and Ro-31-8220, which also inhibited the effects of bFGF, bombesin, and PDGF. Down-regulation of PKC by prolonged treatment with 4 beta phorbol 12-myristate 13-acetate also abolished EGF- and PDGF-stimulated phosphatidylbutanol formation. EGF and bombesin induced biphasic translocations of PKC delta and epsilon to the membrane that were detectable at 15 s. In the presence of Ro-31-8220, translocation of PKC alpha became evident, and membrane association of the delta- and epsilon-isozymes was enhanced and/or sustained in response to the two agonists. The inhibitor also enhanced EGF-stimulated [3H]diacylglycerol formation in cells preincubated with [3H]arachidonic acid, which labeled predominantly phosphatidylinositol, but inhibited [3H]diacylglycerol production in cells preincubated with [3H]myristic acid, which labeled mainly phosphatidylcholine. These data support the conclusion that EGF can stimulate diacylglycerol formation from PtdIns(4,5)P2 and that PKC performs the dual role of down-regulating this response as well as mediating phosphatidylcholine hydrolysis. In summary, all of the results of the study indicate that PLD activation by EGF is downstream of PtdIns(4,5)P2-hydrolyzing phospholipase and is dependent upon subsequent PKC activation. PMID- 7876146 TI - Functional coupling of phosphorylation and nucleotide binding sites in the proteolytic fragments of Na+/K(+)-ATPase. AB - Cleavage of the alpha-subunit of Na+/K(+)-ATPase by trypsin at Arg438-Ala439 causes enzyme inhibition which has been suggested to be due to altered alignment of phosphorylation site on the 48-kDa N-terminal fragment with nucleotide binding site on the 64-kDa C-terminal fragment. Our aims were to test this hypothesis and to assess the effect of the cleavage on the enzyme's two ATP sites. Na(+) dependent phosphorylation of the partially cleaved enzyme by ATP showed that K0.5 values of ATP for phosphorylations of intact alpha and 48-kDa peptide were the same (0.4 microM). Unchanged interactions among the residues across the cleavage site were also indicated by data showing that reaction of fluorescein isothiocyanate with the 64-kDa peptide blocked phosphorylation of the 48-kDa peptide by ATP. ATP is known to block the reaction of fluorescein isothiocyanate with the enzyme. Experiments on the partially cleaved enzyme showed that K0.5 of ATP for protection of alpha was 30-60 microM, and the value for the protection of interacting 48-kDa and 64-kDa peptides was 1-3 mM. Evidently, while the cleavage does not affect the high affinity catalytic site, it disrupts the allosteric low affinity ATP site. Experiments on reconstituted preparations showed that the cleavage abolished ATP-dependent Na+/K+ exchange, Pi+ATP-dependent Rb+/Rb+ exchange, ATP-dependent Na+/Na+ exchange, and ADP+ATP-dependent Na+/Na+ exchange activities. Selective disruption of the low affinity ATP site accounts for the inhibitions of all functions involving K+(Rb+), based on the established role of this site in the control of K+ access channels. Cleavage-induced inhibitions of other activities, however, suggest additional roles of the low affinity ATP site in the reaction cycle. PMID- 7876147 TI - Thyroid hormone influences the maturation of apolipoprotein A-I messenger RNA in rat liver. AB - Chronic administration of thyroid hormone (T3) increases apolipoprotein (apo) A-I gene expression in rat liver. That transcriptional activity of the apoA-I gene is reduced to 50% of control, whereas abundance levels of nuclear and total cellular apoA-I mRNA are increased 3-fold, implies more effective apoA-I mRNA maturation. To study hormonal effects on apoA-I RNA processing, we quantified mRNA precursors in control and T3-treated rats (50 micrograms/100 g body weight for 7 days). Northern blotting, amplification of reverse-transcribed RNA, and ribonuclease protection assays showed that the splicing pathway is branched, in that either intron 1 or intron 2 is removed first from the primary transcript, whereas intron 3 is removed last. In T3-treated rats, abundance levels of the primary transcript, the intron 1-containing precursor devoid of intron 2, the intron 2 containing precursor devoid of intron 1, the intron 3-containing precursor lacking both introns 1 and 2, and nuclear mRNA were 65, 183, 78, 195, and 268% of controls. Compared with control rats, the half-life of the intron 1-containing precursor, measured after injection of actinomycin D, was increased 2-fold in T3 treated rats. In contrast, half-lives of the primary transcript and the intron 2 containing precursor were similar in control and T3-treated rats. Ribonuclease protection assays revealed an RNA species extending from the transcription start site close to the 3' end of intron 1. The abundance of this RNA fragment, probably representing a degradation product, was 2.5-fold higher in control than in T3-treated animals (p < 0.001). Sequences of apoA-I mRNA precursors were identical in control and T3-treated rats which excluded hormonal effects on splice-site selection or post-transcriptional editing of apoA-I transcripts. Compartmental modeling of apoA-I mRNA processing suggested that chronic thyroid hormone administration enhances apoA-I mRNA maturation more than 7-fold by protecting the intron 1-containing precursor devoid of intron 2 from degradation and by facilitating the splicing of intron 1 from this precursor. PMID- 7876148 TI - The dopamine D1D receptor. Cloning and characterization of three pharmacologically distinct D1-like receptors from Gallus domesticus. AB - Three genomic clones encoding dopamine D1-like receptors were isolated from the avian species Gallus domesticus. Two of these genes encode proteins of 451 and 488 amino acids, which, based on deduced amino acid sequence identity and homology of exhibited pharmacological profiles, appear to be species homologs of mammalian and vertebrate D1/D1A and D5/D1B receptors, respectively. The third genomic clone, termed D1D, encodes a protein of 445 amino acids displaying a deduced amino acid sequence identity within putative transmembrane domains of 75% to mammalian D1/D1A and 77% to D5/D1B receptors with overall sequence homologies of only 49% and 46%, respectively. Membranes from COS-7 cells transfected with D1D DNA bound [3H]SCH-23390 in a saturable manner with high affinity (approximately 300 pM) and with a pharmacological profile clearly indicative of a dopamine D1-like receptor. The D1D receptor exhibited affinities for 6,7 dihydroxy-2-aminotetralin and dopamine 10-fold higher than D1/D1A receptors, characteristic of the D5/D1B receptor subfamily. In contrast, the D1D receptor bound dopaminergic agents, such as SKF-38393, apomorphine, pergolide, and lisuride, with affinities 10-fold higher than other cloned mammalian or vertebrate D1A/D1B receptor subtypes, while both clozapine and haloperidol displayed considerably lower affinity for the D1D receptor. Based on the low overall amino acid sequence identity (54%) and unique pharmacological profile, the avian dopamine D1D receptor does not appear to be a species homolog of the recently cloned vertebrate D1C receptor (Sugamori, K.S., Demchyshyn, L. L., Chung, M., and Niznik, H. B. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 10536 10540). As with all cloned mammalian and vertebrate D1-like receptors, the D1D receptor stimulates adenylate cyclase activity in the presence of dopamine or SKF 82526. Northern blot analysis reveals the selective expression of both avian D1D and D1A receptor mRNAs only in brain with the D1B receptor more widely distributed and localized in tissues such as brain, kidney, and spleen. The isolation of four distinct vertebrate dopamine D1 receptor subtypes suggests the existence of additional mammalian D1 like receptor genes that may account for the observed pharmacological and biochemical multiplicity of dopamine D1-like receptor mediated events. PMID- 7876149 TI - Distinct functions of the Fc epsilon R1 gamma and beta subunits in the control of Fc epsilon R1-mediated tyrosine kinase activation and signaling responses in RBL 2H3 mast cells. AB - In RBL-2H3 rat tumor mast cells, cross-linking the high affinity IgE receptor, Fc epsilon R1, activates the protein-tyrosine kinases Lyn and Syk and initiates a series of responses including protein-tyrosine phosphorylation, inositol 1,4,5 trisphosphate synthesis, Ca2+ mobilization, secretion, membrane ruffling, and actin plaque assembly. The development of chimeric receptors containing cytoplasmic domains of individual subunits of the heterotrimeric (alpha beta gamma 2) Fc epsilon R1 has simplified analyses of early signaling events in RBL 2H3 cells. Here, RBL-2H3 cells were transfected with cDNAs encoding the extracellular and transmembrane domains of the interleukin-2 receptor alpha subunit (the Tac antigen) joined to the C-terminal cytoplasmic domains of the Fc epsilon R1 gamma and beta subunits (TT gamma and TT beta). Both sequences contain tyrosine activation motifs implicated in antigen receptor signal transduction. TT gamma and TT beta are expressed independently of the native Fc epsilon R1, as demonstrated by the ability of Tac cross-linking agents to trigger the clustering and internalization through coated pits of both chimeric receptors without co clustering the Fc epsilon R1. A full range of signaling activities is induced by TT gamma cross-linking; the TT gamma-induced responses are slower and, except for Lyn activation, smaller than the Fc epsilon R1-induced responses. In striking contrast, TT beta cross-linking elicits no tyrosine phosphorylation or signaling responses, it impairs basal activities measured in secretion and anti-PY (anti phosphotyrosine antibody) immune complex kinase assays, and it antagonizes Fc epsilon R1-induced Lyn and Syk activation, protein-tyrosine phosphorylation, and signaling responses. We hypothesize that the isolated beta subunit binds a specific kinase or coupling protein(s) required for signaling activity, sequestering it from the signal-transducing gamma subunit. Binding the same kinase or coupling protein to the beta subunit of the intact Fc epsilon R1 may serve instead to present it to the adjacent gamma subunit, resulting in enhanced kinase activation and signaling responses. PMID- 7876150 TI - Characterization of the COOH terminus of non-muscle caldesmon mutants lacking mitosis-specific phosphorylation sites. AB - Phosphorylation of rat non-muscle caldesmon by cdc2 kinase causes reduction in most of caldesmon's properties, including caldesmon's binding to actin, myosin, and calmodulin, as well as its inhibition of actomyosin ATPase. We have generated and characterized the COOH terminus of caldesmon mutants lacking mitosis-specific phosphorylation sites, because the COOH-terminal half of caldesmon contains all 7 putative Ser or Thr sites for cdc2 kinase. Codons for the 7 putative Ser or Thr residues have been mutated to Ala, and resultant mutants were bacterially expressed. Analyses of the phosphopeptide maps of these mutants have identified 6 sites, including Ser-249, Ser-462, Thr-468, Ser-491, Ser-497, and Ser-527 as the mitosis-specific phosphorylation sites, whereas the phosphorylation of the remaining site, Thr-377, is not detected by this assay method. Actin binding experiments have suggested that 5 sites including Ser-249, Ser-462, Thr-468, Ser 491, and Ser-497 are important for the phosphorylation-dependent reduction in actin binding. Characterization of a mutant lacking all 7 Ser or Thr sites (7 fold mutant) has revealed that 7-fold mutation eliminates all phosphorylation sites by cdc2 kinase. While the in vitro properties of the 7-fold mutant, including actin, myosin, and calmodulin binding and inhibition of actomyosin ATPase, are very similar to those of nonmutated protein, such properties are not affected by the treatment with cdc2 kinase in contrast to nonmutated protein. This mutant should thus be useful to explore the functions of the mitosis specific phosphorylation of caldesmon. PMID- 7876151 TI - The U1 small nuclear ribonucleoprotein/5' splice site interaction affects U2AF65 binding to the downstream 3' splice site. AB - In the gene of the neural cell adhesion molecule, the 5' splice site of the alternate exon 18 plays an important role in establishing regulated splicing profiles. To understand how the 5' splice site of exon 18 contributes to splicing regulation, we have investigated the interaction of the U2AF65 splicing factor to pre-mRNAs that contained portions of the constitutive exon 17 or the alternate exon 18 fused to exon 19 and separated by a shortened intron. Despite sharing an identical 3' splice site, only the pre-mRNA that contained a portion of exon 17 and its associated 5' splice site displayed efficient U2AF65 cross-linking. Strikingly, a G-->U mutation at position +6 of the intron, converting the 5' splice site of exon 18 into that of exon 17, stimulated U2AF65 crosslinking. The improved cross-linking efficiency of U2AF65 to a pre-mRNA carrying the 5' splice site of exon 17 required the integrity of the 5' end of U1 but not of U2 small nuclear RNA. Our results indicate that neural cell adhesion molecule 5' splice site sequences influence U2AF65 binding through a U1 small nuclear ribonucleoprotein/U2AF interaction that occurs at the commitment stage of spliceosome assembly, before stable binding of the U2 small nuclear ribonucleoprotein. Thus, the 5' splice sites of exons 17 and 18 differentially affect U2AF65 binding to the 3' splice site of exon 19. Factors that modulate U1 small nuclear ribonucleoprotein binding to these 5' splice sites may play a critical role in regulating exon 18 skipping. PMID- 7876152 TI - Functional analysis of a dominant negative mutant of G alpha i2. AB - The key event in receptor-catalyzed activation of heterotrimer G proteins is binding of GTP, which leads to subunit dissociation generating GTP-bound alpha subunits and free beta gamma complexes. We have previously identified a mutation that abolished GTP binding in G alpha o (S47C) and demonstrated that the mutant retained the ability to bind beta gamma and could act in a dominant negative fashion when expressed in Xenopus oocytes (Slepak, V.Z., Quick, M.W., Aragay, A.M., Davidson, N., Lester, H.A., and Simon, M.I. (1993) J. Biol. Chem. 268, 21889-21894). In the current work, we investigated the effects of the homologous mutant of G alpha i2 (S48C) upon signaling pathways reconstituted in transiently transfected COS-7 cells. We found that expression of the G alpha i2 S48C mutant prevented stimulation of phospholipase C (PLC) beta 2 by free beta gamma subunit complexes. This effect of G alpha i S48C was not readily reversible in contrast to the inhibitory effect of wild-type G alpha i2, which could be reversed upon activation of the cotransfected muscarinic M2 receptor, presumably by release of beta gamma from the G protein heterotrimer. Coexpression of G alpha i S48C or the wild-type G alpha i2 also dramatically decreased G16-mediated stimulation of PLC by C5a in the cells transfected with cDNAs encoding C5a receptor and G alpha 16. Activation of PLC via endogenous Gq or G11 in the presence of alpha 1C adrenergic receptors was similarly attenuated by coexpression of G alpha i or G alpha i S48C. Pertussis toxin treatment of the transfected cells enhanced the inhibition of the receptor-stimulated PLC by wild-type G alpha i subunits but did not influence the effects of the dominant negative mutant. The enhancement of the wild-type G alpha i inhibitory effect by pertussis toxin can be explained by stabilization of G alpha i binding to beta gamma as a result of ADP-ribosylation, while G alpha i S48C mutant binds beta gamma irreversibly even without pertussis toxin treatment. Therefore, a feasible mechanism to rationalize the attenuation of the G alpha 16 and Gq/11-mediated activation of PLC by cotransfected G alpha i is the competition between G alpha i and G alpha 16 or Gq/11 for the beta gamma complexes, which are necessary for the G protein coupling with receptors. These experiments provide new evidence for the role of beta gamma in the integration of signals controlling phosphoinositide release through different G alpha families. PMID- 7876153 TI - Role of partner homology in DNA recombination. Complementary base pairing orients the 5'-hydroxyl for strand joining during Flp site-specific recombination. AB - Absolute homology between partner substrates within the strand exchange region is an essential requirement for recombination mediated by the yeast site-specific recombinase Flp. Using combinations of specially designed half- and full-site Flp substrates, we demonstrate that the strand joining step of recombination is exquisitely sensitive to spacer homology. At each exchange point, 2-3 spacer nucleotides adjacent to the nick within the cleaved strand of one substrate must base pair with the corresponding segment of the un-nicked strand from the second substrate for efficient strand joining in the recombinant mode. In accordance with the "cis-activation/trans-nucleophilic attack" model for each of the two transesterification steps of Flp recombination (strand cleavage and strand joining), we propose that the limited strand pairing orients the DNA-nucleophile (5'-hydroxyl) for attack on its target diester (3'-phosphotyrosyl-Flp). During one round of recombination, 4-6 terminal base pairs of the spacer (2-3 base pairs at each spacer end) must unpair, following strand cleavage, within a DNA substrate and pair with the partner substrate prior to strand union. In this model, the extent of branch migration of the covalently closed Holliday intermediate is limited to the central core of the spacer. The templated positioning of reactive nucleic acid groups (which is central to the model) may be utilized by other recombination systems and by RNA splicing reactions. PMID- 7876154 TI - Characterization of the molecular defect in factor VR506Q. AB - A poor anticoagulant response of plasma to activated protein C is correlated with a single mutation in the factor V molecule (Arg506-->Gln). Factor V was purified to homogeneity from plasma of two unrelated patients (patient I, factor VI, and patient II, factor VII), who are homozygous for this mutation. The factor V molecule from both patients has normal procoagulant activity when compared with factor V isolated from normal plasma in both a clotting time-based assay and in an assay measuring alpha-thrombin formation. The cleavage and subsequent inactivation by activated protein C (APC) of the alpha-thrombin-activated membrane-bound cofactor (factor Va) from both patients were analyzed and compared with the cleavage and inactivation of normal human factor Va. In normal factor Va, cleavage at Arg506 generates a M(r) = 75,000 fragment and a M(r) = 28,000/26,000 doublet and is necessary for the optimum exposure of the sites for subsequent cleavage at Arg306 and Arg679. Proteolysis at these sites leads to the appearance of M(r) - 45,000 and 30,000 fragments and a M(r) = 22,000/20,000 doublet. Cleavage at Arg306 is membrane-dependent and is required for complete inactivation. Following 5 min of incubation with APC (5.4 nM) membrane-bound normal factor Va (280 nM) has virtually no cofactor activity whereas under similar experimental conditions factor VaI and factor VaII retain approximately 50% of their initial activity. After 1 h of incubation with APC, factor VaI retains 20% of its initial cofactor activity whereas factor VaII has 10% remaining cofactor activity. The initial loss in cofactor activity (approximately 70%) of membrane-bound factor VaI and factor VaII during the first 10 min of the inactivation reaction is correlated with cleavage at Arg306 and appearance of a M(r) = 45,000 fragment and a M(r) = 62,000/60,000 doublet. Subsequently, the M(r) = 62,000/60,000 doublet is cleaved at Arg679 to generate a M(r) = 56,000/54,000 doublet resulting in complete loss of cofactor activity. Both procofactors, factor VI and factor VII, were inactivated following cleavage at Arg306 and Arg679, with APC inactivation rates equivalent to those observed for normal factor V. Our data demonstrate that: 1) cleavage at Arg506 is required for optimum exposure of the cleavage sites at Arg306 and Arg679 and rapid inactivation of membrane-bound factor Va; and 2) cleavage at Arg306 by APC on membrane-bound factor V occurs at the same rate in both normal and APC-resistant individuals. Thus cleavage at Arg306 and Arg679 and subsequent inactivation of the membrane-bound procofactor, factor V, does not require prior cleavage at Arg506 for optimum exposure. PMID- 7876155 TI - Basolateral secretion of amyloid precursor protein in Madin-Darby canine kidney cells is disturbed by alterations of intracellular pH and by introducing a mutation associated with familial Alzheimer's disease. AB - The analysis of potential sorting signals in amyloid precursor protein (APP) by site-directed mutagenesis and the disturbance of metabolic pathways by drugs is used here to define the parameters that determine polarized secretion of APP in Madin-Darby canine kidney cells. Endogenously produced APP751/770 and APP695 produced from transfected constructs are secreted almost exclusively into the basolateral compartment. The sorting mechanism is highly dependent on intracellular pH as demonstrated by its sensitivity to primary amines and inhibitors of the acidifying vacuolar protein ATPase. The role of potential basolateral sorting signals in the cytoplasmic, transmembrane, and beta A4 amyloid region of APP was investigated. Neither deletion of the endocytosis and putative basolateral sorting signal GY.NPTY nor complete deletion of the cytoplasmic domain causes apical secretion of soluble APP. Further deletion of the transmembrane domain and of the beta A4 amyloid region confirmed that the major basolateral sorting determinant resides in the extracellular domain of APP. Increased beta-secretase cleavage of APP after introduction of the "swedish" double mutation causes apical missorting of about 20% of beta-secretase-cleaved APP. The data underline the complexity of processing and sorting APP in polarized cells and suggest a possible problem of protein sorting in Alzheimer's Disease. PMID- 7876156 TI - Developmental regulation of expression and activity of multiple forms of the Drosophila RAC protein kinase. AB - We have characterized the Drosophila homologue of the proto-oncogenic RAC protein kinase (DRAC-PK). The DRAC-PK gene gives rise to two transcripts with the same coding potential, generated by the use of two different polyadenylation signals. Each transcript encodes two polypeptides because of the presence of a weaker initiator ACG codon, upstream from the major AUG, such that the larger protein contains an N-terminal extension. Like the human isoforms, DRAC-PKs possess a novel signaling region, the pleckstrin homology domain. DRAC-PK proteins have a similar expression pattern, being regulated both maternally and zygotically, and are expressed throughout Drosophila development. Antisera specific for recombinant DRAC-PK and for its C terminus detected two polypeptides of 66 and 85 kDa in Drosophila extracts. The antirecombinant antisera also recognized a polypeptide of 120 kDa from Drosophila, which apparently shared an epitope related to DRAC-PK sequences. The role of p120 appears to be restricted compared with that of DRAC-PK, since it was not detected in larvae or adult flies. There was no spatial restriction of DRAC-PK expression during embryogenesis, suggesting that localized activation might be a regulatory mechanism for its function. DRAC PK possesses an intrinsic kinase activity that is approximately 8-fold higher in adult flies than in 0-3-h embryos undergoing rapid mitotic cycles. PMID- 7876157 TI - Purification and characterization of an isoaspartyl dipeptidase from Escherichia coli. AB - We have identified a gene (iadA) in Escherichia coli encoding a 41-kDa polypeptide that catalyzes the hydrolytic cleavage of L-isoaspartyl, or L-beta aspartyl, dipeptides. We demonstrate at least a 3000-fold purification of the enzyme to homogeneity from crude cytosol. From the amino-terminal amino acid sequence obtained from this preparation, we designed an oligonucleotide that allowed us to map the gene to the 98-min region of the chromosome and to clone and obtain the DNA sequence of the gene. Examination of the deduced amino acid sequence revealed no similarities to other peptidases or proteases, while a marked similarity was found with several dihydroorotases and imidases, reflecting the similarity in the structures of the substrates for these enzymes. Using an E. coli strain containing a plasmid overexpressing this gene, we were able to purify sufficient amounts of the dipeptidase to characterize its substrate specificity. We also examined the phenotype of two E. coli strains where this isoaspartyl dipeptidase gene was deleted. We inserted a chloramphenicol cassette into the disrupted coding region of iadA in both a parent strain (MC1000) and a derivative strain (CL1010) lacking pcm, the gene encoding the L-isoaspartyl methyltransferase involved in the repair of isomerized proteins. We found that the iadA deletion does not result in reduced stationary phase or heat shock survival. Analysis of isoaspartyl dipeptidase activity in the deletion strain revealed a second activity of lower native molecular weight that accounts for approximately 31% of the total activity in the parent strain MC1000. The presence of this second activity may account for the absence of an observable phenotype in the iadA mutant cells. PMID- 7876159 TI - Positive and negative regulation of D-type cyclin expression in skeletal myoblasts by basic fibroblast growth factor and transforming growth factor beta. A role for cyclin D1 in control of myoblast differentiation. AB - Differentiation of skeletal myoblasts in culture is negatively regulated by certain growth factors, including basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF beta). We investigated the effects of bFGF and TGF beta on D-type cyclin expression in skeletal myoblasts. When myoblasts were induced to differentiate in low mitogen medium, expression of cyclin D1 rapidly fell below detectable levels. In contrast, expression of cyclin D3 increased to levels exceeding those present in myoblasts. Expression of cyclin D1 was induced in myoblasts by bFGF and TGF beta (albeit with different kinetics for each factor), while induction of cyclin D3 expression was inhibited by these growth factors. Although these results are consistent with other reports showing induction of cyclin D1 by growth factors, induction of cyclin D3 expression during terminal differentiation of myoblasts and inhibition of this induction by growth factors is surprising. These results suggest that cyclin D3, previously thought to be only a positive regulator of cell cycle progression, may also function in the cellular context of terminal differentiated muscle. Stable expression of cyclin D1 from an ectopic viral promoter inhibits C2C12 myoblast differentiation, but only in those clones where the level of cyclin D1 expression does not significantly exceed that present in control myoblasts stimulated by bFGF. Together, these result suggest that cyclin D1 expression functions in the inhibition of myoblast differentiation by certain growth factors. PMID- 7876158 TI - Ceramide reverses brefeldin A (BFA) resistance in BFA-resistant cell lines. AB - We have found that C6 ceramide, a cell-permeable ceramide analog, partially restored the brefeldin A (BFA) sensitivity in a BFA-resistant mutant of Vero cells (BER-40) and in the naturally BFA-resistant Madin-Darby canine kidney (MDCK) cells. Incubation of BER-40 and MDCK cells with low concentrations of C6 ceramide resulted in (i) a pronounced increase in BFA cytotoxicity as measured by the inhibition of [3H]thymidine incorporation and the inhibition of colony formation by BFA, (ii) a significant protection by BFA against ricin cytotoxicity, and (iii) an inhibition of bulk protein secretion by BFA in BER-40 and MDCK cells. Related sphingolipids including sphingosine, sphingomyelin, and lactosylceramide and other unrelated lipid second messengers such as arachidonic acid and 1,2-diacylglycerol did not elicit the protection of BER-40 and MDCK cells against ricin cytotoxicity by BFA. C6 ceramide was the most effective among the ceramides with different acyl chain lengths. Interestingly, dihydro-C6 ceramide, which lacks the trans double bond in the sphingoid base, had no effect. On the other hand, C6 ceramide did not enhance BFA sensitivity in BFA-sensitive Vero cells. The LD50 of C6 ceramide were similar in Vero and BER-40 cells. Fluorescence microscopic studies revealed that C6 ceramide induced the redistribution of beta-COP from the Golgi membranes to a more dispersed localization in both BFA-sensitive and BFA-resistant cell lines, mimicking the effect of BFA. Suboptimal concentration of C6 ceramide also restored the effect of BFA on the beta-COP distribution in BER-40 and MDCK cells. These results indicate that C6 ceramide restores the BFA sensitivity in BFA-resistant BER-40 and MDCK cells. PMID- 7876160 TI - Regulation of GATA-2 phosphorylation by mitogen-activated protein kinase and interleukin-3. AB - GATA-2 is a member of a family of transcription factors which bind a common DNA sequence motif (WGA-TAR) through an evolutionarily conserved zinc finger domain. An essential role for GATA-2 in the development of hematopoietic stem cells has recently been shown in gene targeting experiments in mice. Here we show that GATA 2 exists in hematopoietic progenitor cells as a phosphoprotein. Stimulation of progenitors with interleukin-3 (IL-3) results in enhanced phosphorylation of GATA 2 which occurs within 5 min. IL-3 is known to signal in part through mitogen activated protein (MAP) kinase, and evidence for MAP kinase signaling in the control of GATA-2 phosphorylation was obtained by genetically manipulating the MAP kinase pathway in COS cells using either constitutively activating or interfering mutants of MAP kinase kinase. Furthermore, using an interfering mutant of MAP kinase kinase, we directly demonstrated a critical role for the MAP kinase pathway in the IL-3-dependent phosphorylation of GATA-2 in hematopoietic progenitor cells. Finally, in vitro phosphorylation experiments using recombinant GATA-2 raise the possibility that MAP kinase itself may phosphorylate GATA-2. Our results provide evidence for phosphorylation via the MAP kinase pathway constituting a cytoplasmic link between GATA-2 and growth factor receptors and are consistent with the hypothesis that GATA-2 is involved in the growth factor responsiveness and proliferation control of hematopoietic progenitor cells. PMID- 7876161 TI - High level expression and characterization of the mitochondrial citrate transport protein from the yeast Saccharomyces cerevisiae. AB - The gene encoding the mitochondrial citrate transport protein (CTP) in the yeast Saccharomyces cerevisiae has been identified, and its protein product has been overexpressed in Escherichia coli. The expressed CTP accumulates in inclusion bodies and can be solubilized with sarkosyl. Approximately 25 mg of solubilized CTP at a purity of 75% is obtained per liter of E. coli culture. The function of the solubilized CTP has been reconstituted in a liposomal system where both its kinetic parameters (i.e. Km = 0.36 mM and Vmax = 2.5 mumol/min/mg protein) and its substrate specificity have been determined. Notably, the yeast CTP displays a stricter specificity for tricarboxylates than do CTPs from higher eukaryotic organisms. Dot matrix analysis of the yeast CTP sequence indicates the presence of three homologous sequence domains (each approximately 100 residues in length), which are also related to domains in other CTPs. Thus, the yeast CTP displays the tripartite structure characteristic of other mitochondrial transporters. Alignment of the yeast CTP sequence with CTPs from other sources defines a consensus sequence that displays 89 positions of amino acid identity, as well as the more generalized mitochondrial transporter-associated sequence motif. Based on hydropathy analysis, the yeast CTP contains six putative membrane-spanning alpha-helices. Finally, Southern blot analysis indicates that the yeast genome contains a single gene encoding the mitochondrial CTP. Our data indicate that, based on both its structural and functional properties, the expressed yeast CTP can be assigned membership in the mitochondrial carrier family. The identification of the yeast CTP gene, and the expression and purification of large quantities of its protein product, pave the way for investigations into the roles of specific amino acids in the CTP translocation mechanism, as well as for the initiation of crystallization trials. PMID- 7876162 TI - The serine-rich Entamoeba histolytica protein is a phosphorylated membrane protein containing O-linked terminal N-acetylglucosamine residues. AB - Previously, we described the isolation of a cDNA clone and the gene encoding a protective antigen of the protozoan parasite Entamoeba histolytica, the serine rich Entamoeba histolytica protein (SREHP). The derived amino acid sequence of the SREHP cDNA clone was remarkable for a high serine content (52/233 amino acids), a putative signal sequence, multiple hydrophilic dodecapeptide and octapeptide tandem repeats, and a hydrophobic C-terminal putative membrane spanning region. Here, we show that SREHP is modified by the addition of phosphate at serine residues, O-linked terminal N-acetylglucosamine residues, and by acylation. When the SREHP gene is expressed in baculovirus transformed Sf-9 cells, the product is also phosphorylated and glycosylated and is localized to the plasma membrane of the insect cells. The native SREHP molecule also serves as a potent chemoattractant for amebic trophozoites. The data presented here suggest that SREHP is a unique membrane protein with phosphorylation and glycosylation patterns usually associated with nuclear or cytoplasmic proteins. PMID- 7876163 TI - Independent signaling of grp78 gene transcription and phosphorylation of eukaryotic initiator factor 2 alpha by the stressed endoplasmic reticulum. AB - Perturbation of endoplasmic reticular (ER) function signals increased expression of the gene encoding the ER resident chaperone Grp78/BiP and rapid suppression of translational initiation accompanied by phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF-2). eIF-2 alpha phosphorylation and grp78 mRNA induction were measured in GH3 pituitary cells subjected to varied degrees of ER stress to ascertain whether activation of an eIF-2 alpha kinase is involved in both events. grp78 mRNA was induced at low concentrations of ionomycin and dithiothreitol that did not provoke eIF-2 alpha phosphorylation or inhibition of amino acid incorporation. Mobilization of the bulk of cell-associated Ca2+ and the induction of grp78 mRNA occurred at comparable low concentrations of ionomycin, whereas phosphorylation of eIF-2 alpha and inhibition of protein synthesis required higher ionophore concentrations. Pretreatment for 1 h with cycloheximide suppressed grp78 mRNA induction and eIF-2 alpha phosphorylation in response to either stressor. Prolonged (17 h) cycloheximide blockade increased eIF-2 alpha phosphorylation without inducing grp78 mRNA. Upon release from the blockade, grp78 mRNA was induced and eIF-2 alpha was dephosphorylated. Translational tolerance to ionomycin or dithiothreitol, accompanied by dephosphorylation of eIF-2 alpha, was observed whenever grp78 mRNA was induced. Induction of grp78 mRNA preceded significant eIF-2 alpha phosphorylation during treatment with brefeldin A. It is concluded that signaling of grp78 gene transcription can occur independently of eIF-2 alpha phosphorylation or translational repression and that greater degrees of ER stress are required for eIF-2 alpha phosphorylation than for grp78 mRNA induction. PMID- 7876164 TI - 2-5A-dependent RNase molecules dimerize during activation by 2-5A. AB - 2-5A-dependent RNase is an interferon-inducible enzyme that requires 5' phosphorylated, 2',5'-linked oligoadenylates (2-5A) for its endoribonuclease activity against single-stranded RNAs. We demonstrate here that recombinant, human 2-5A-dependent RNase forms stable homodimers during its stimulation by 2 5A. The protein dimers were observed to form only upon binding to 2-5A, as shown using gel filtration chromatography and chemical cross-linking and after centrifugation in glycerol gradients. A monoclonal antibody to 2-5A-dependent RNase was prepared and used to probe the subunit structure of the enzyme in the presence or absence of 2-5A. Using oligoadenylates of different length, structure, and 5'-phosphorylation states we determined that conversion of 2-5A dependent RNase from its monomeric, inactive form to its homodimeric, active form required the presence of functional 2-5A. These results demonstrate that the catalytically active form of 2-5A-dependent RNase is a homodimer. PMID- 7876165 TI - A similar DNA-binding motif in NFAT family proteins and the Rel homology region. AB - The cyclosporin-sensitive factor NFATp cooperates with Fos and Jun family proteins to regulate transcription of the interleukin 2 gene in activated T cells. We have defined a 187-amino-acid fragment of NFATp, located centrally within the protein sequence, as the minimal region required for DNA binding and for complex formation with Fos and Jun. The sequence of this region of NFATp shows a low degree of similarity to the Rel homology region. One specific short sequence in NFATp (RAHYETEG), located near the NH2 terminus of the DNA-binding domain, resembles a highly conserved sequence (RFRYxCEG) that is located near the NH2 terminus of the Rel homology region and that has been implicated in DNA binding by Rel family proteins. Mutational analysis demonstrates that the residues in this sequence that are identical in NFATp and Rel family proteins contribute to DNA binding by NFATp. Further, mutation of the threonine residue in this sequence to cysteine, as in Rel proteins, confers on NFATp a sensitivity to sulfhydryl modification similar to that of Rel family proteins. The results suggest that NFATp and Rel family proteins bind to DNA using similar structural motifs. PMID- 7876166 TI - The copper-containing dissimilatory nitrite reductase involved in the denitrifying system of the fungus Fusarium oxysporum. AB - A copper-containing nitrite reductase (Cu-NiR) was purified to homogeneity from the denitrifying fungus Fusarium oxysporum. The enzyme seemed to consist of two subunits with almost the same M(r) value of 41,800 and contains two atoms of copper per subunit. The electron paramagnetic resonance spectrum showed that both type 1 and type 2 copper centers are present in the protein, whereas the visible absorption spectrum exhibited a sole and strong absorption maximum at 595 nm, causing a blue but not green color. The reaction product due to the Cu-NiR was mainly nitric oxide (NO), whereas a stoichiometric amount of nitrous oxide (N2O) was formed when cytochrome P-450nor was further added to the assay system. Therefore, the denitrifying (N2O forming) nitrite reductase activity that we had detected in the cell-free extract of the denitrifying cells (Shoun, H., and Tanimoto, T. (1991) J. Biol. Chem. 266, 11078-11082) could be reconstituted upon combination of the purified Cu-NiR and P-450nor. The Km for nitrite and specific activity at pH 7.0 were estimated as 49 microM and 447 mumol NO.min-1.mg protein 1, respectively. Its activity was strongly inhibited by cyanide, carbon monoxide, and diethyldithiocarbamate, whereas enormously restored by the addition of cupric ions. An azurin-like blue copper protein (M(r) = 15,000) and a cytochrome c were also isolated from the same fungus, both of which together with cytochrome c of the yeast Saccharomyces cerevisiae were effective in donating electrons to the fungal Cu-NiR. The result suggested that the physiological electron donor of the Cu-NiR is the respiratory electron transport system. The intracellular localization of Cu-NiR was investigated, and it was suggested that the Cu-NiR localizes in an organelle such as mitochondrion. These findings showed the identity in many aspects between the fungal nitrite reductase and bacterial dissimilatory Cu-NiRs. This is the first isolation of dissimilatory NiR from a eukaryote. PMID- 7876167 TI - DNA repair protein XPA binds replication protein A (RPA). AB - XPA is a zinc finger DNA-binding protein, which is missing or altered in group A xeroderma pigmentosum cells and known to be involved in the damage-recognition step of the nucleotide excision repair (NER) processes. Using the yeast two hybrid system to search for proteins that interact with XPA, we obtained the 34 kDa subunit of replication protein A (RPA, also known as HSSB and RFA). RPA is a stable complex of three polypeptides of 70, 34, 11 kDa and has been shown to be essential in the early steps of NER as well as in replication and recombination. We also demonstrate here that the RPA complex associates with XPA. These results suggest that RPA may cooperate with XPA in the early steps of the NER processes. PMID- 7876168 TI - Establishment of lipopolysaccharide-dependent nuclear factor kappa B activation in a cell-free system. AB - Nuclear factor kappa B (NF-kappa B), consisting of p50 and p65, is bound to a cytoplasmic retention protein, I kappa B, in a resting state, and the stimulation of cells with a variety of inflammatory stimuli induces the dissociation of NF kappa B from I kappa B and the nuclear translocation of NF-kappa B, thereby activating several genes involved in inflammatory responses, such as interleukin (IL)-6, IL-8, and tumor necrosis factor alpha. In order to elucidate the precise mechanism of NF-kappa B activation, we have established lipopolysaccharide (LPS) dependent NF-kappa B activation in a cell-free system using plasma membrane enriched, cytosol, and nuclear fractions extracted from a human monocytic cell line, THP-1, by disruption with sonication followed by a differential centrifugation. The combination of plasma membrane-enriched fraction and cytosol was sufficient to activate NF-kappa B in a LPS/CD14-dependent manner only in the presence of ATP as judged by the binding of NF-kappa B to the IL-8 gene kappa B site on an electrophoretic mobility shift assay. LPS-dependent NF-kappa B activation was inhibited by protein kinase inhibitors, such as staurosporine, herbimycin A, tyrphostin, and genistein, but not mitogen-activated protein kinase substrate, cGMP-dependent protein kinase, cAMP-dependent protein kinase, protein kinase C, and calmodulin-dependent protein kinase II inhibitory peptides, suggesting that staurosporine-sensitive kinase(s) as well as tyrosine kinase(s) are involved in LPS-mediated NF-kappa B activation. In addition, LPS induced the phosphorylation of I kappa B-alpha, starting at 5 min after the stimulation in a cell-free system. Moreover, the phosphorylation was inhibited by herbimycin A and tyrphostin, but not staurosporine, suggesting that these protein kinase inhibitors act at distinct steps of signal transmission. Establishment of ligand dependent activation of NF-kappa B in a cell-free system will facilitate identification of protein kinase(s) and its substrate(s) involved in LPS-mediated NF-kappa B activation. PMID- 7876169 TI - Molecular determinants conferring alpha-toxin resistance in recombinant DNA derived acetylcholine receptors. AB - Sequences of the alpha-subunits of the nicotinic acetylcholine receptor from the snake and mongoose contain several differences in the region between amino acids 183 and 200. Receptors from both of these species reveal resistance to the snake alpha-toxins presumably arising as a protective evolutionary mechanism. Sequence differences include the added glycosylation signals at residue 187 in the mongoose and at residues 189 and 111 in snake. Although previous observations with peptides and fusion proteins either synthesized chemically or in a bacterial expression system indicate that certain amino acid residues may contribute to the resistance, our findings with the intact receptor in an eukaryotic expression system indicate the major role for glycosylation. In this study, we show that addition of glycosylation signals gives rise to virtually complete glycosylation at the added sites, although heterogeneity of oligosaccharide processing is evident. By analysis of combinations of mutants, we document that glycosylation exerts the predominant influence on alpha-toxin binding. Substitutions at other residues are largely without influence as single mutations but appear to decrease affinity further in multiple mutants, particularly where the receptor is glycosylated at the 187 and 189 positions. Glycosylation exerts a major influence on the dissociation as well as the association rates of the alpha-toxin-receptor complex, suggesting that the decrease for alpha-toxin affinity is not simply a consequence of restricted diffusional access, rather glycosylation affects the conformation and stability of the bound complex. PMID- 7876170 TI - Purification and characterization of heparan sulfate 6-sulfotransferase from the culture medium of Chinese hamster ovary cells. AB - Heparan sulfate 6-sulfotransferase, which catalyzes the transfer of sulfate from 3'-phosphoadenylyl sulfate to position 6 of N-sulfoglucosamine in heparan sulfate, was purified 10,700-fold to apparent homogeneity with a 40% yield from the serum-free culture medium of Chinese hamster ovary cells. The isolation procedure included affinity chromatography of the first heparin-Sepharose CL-6B column (stepwise elution), 3',5'-ADP-agarose, and the second heparin-Sepharose CL 6B column (gradient elution). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme showed two protein bands with molecular masses of 52 and 45 kDa. Both proteins appeared to be glycoproteins, because their molecular masses decreased after N-glycanase digestion. When completely desulfated and N-resulfated heparin was used as acceptor, the purified enzyme transferred sulfate to position 6 of N-sulfoglucosamine residue but did not transfer sulfate to the amino group of glucosamine residue or to position 2 of the iduronic acid residue. Heparan sulfate was also sulfated by the purified enzyme at position 6 of N-sulfoglucosamine residue. Chondroitin and chondroitin sulfate did not serve as acceptors. The optimal pH for enzyme activity was around 6.3. The enzyme activity was inhibited by dithiothreitol and was stimulated strongly by protamine. The Km value for adenosine 3'-phosphate 5'-phosphosulfate was 0.44 microM. PMID- 7876171 TI - What reassorts when reovirus genome segments reassort? PMID- 7876172 TI - Site-directed mutagenesis of P2U purinoceptors. Positively charged amino acids in transmembrane helices 6 and 7 affect agonist potency and specificity. AB - Two subtypes of G protein-coupled receptors for nucleotides (P2U and P2Y purinoreceptors) contain several conserved positively charged amino acids in the third, sixth, and seventh putative transmembrane helices (TMHs). Since the fully ionized form of nucleotides has been shown to be an activating ligand for both P2U and P2Y purinoceptors (P2UR and P2YR), we postulated that some of these positively charged amino acids are involved in binding of the negatively charged phosphate groups of nucleotides. To investigate the role of the conserved positively charged amino acids in purinoceptor function, a series of mutant P2UR cDNAs were constructed so that lysine 107 and arginine 110 in TMH 3, histidine 262 and arginine 265 in TMH 6, and arginine 292 in TMH 7 were changed to the neutral amino acid leucine or isoleucine. The mutated P2UR cDNAs were stably expressed in 1321N1 astrocytoma cells and receptor activity was monitored by quantitating changes in the concentration of intracellular Ca2+ upon stimulation with full (ATP, UTP) or partial (ADP, UDP) P2UR agonists. Neutralization of His262, Arg265, or Arg292 caused a 100-850-fold decrease in the potency of ATP and UTP relative to the unmutated P2UR and rendered ADP and UDP ineffective. In contrast, neutralization of Lys107 or Arg110 did not alter the agonist potency or specificity of the P2UR. Neutralization of Lys289 in the P2UR, which is expressed as a glutamine residue in the P2Y subtype, did not alter receptor activity; however, a conservative change from lysine to arginine at this position altered the rank order of agonist potency so that ADP and UDP were approximately 100-fold more potent than ATP and UTP. A three-dimensional model of the P2UR indicates the feasibility of His262, Arg265, and Arg292 interactions with the phosphate groups of nucleotides. PMID- 7876173 TI - Bovine brain GO isoforms have distinct gamma subunit compositions. AB - The gamma subunit composition of the major bovine brain Go and Gi proteins (GOA, GOB, GOC, Gi1, and Gi2) was characterized using antibodies against specific gamma isoforms. Each of the purified G protein heterotrimers contained a heterogeneous population of gamma subunits, and the profiles of the gamma subunits found with Gi1, Gi2, and GOA were similar. In contrast, each GO isoform had a distinct pattern of associated gamma subunits. These differences were surprising given that all three alpha O isoforms are thought to share a common amino-terminal sequence important for the binding of beta gamma dimers and that the alpha OA and alpha OC proteins may come from the same alpha O1 mRNA. The free alpha OA and alpha OC subunits had unique elution behaviors during MonoQ chromatography, compatible with differences in their post-translational processing. These results indicate that both the alpha and gamma subunit compositions of heterotrimers define the structure of an intact G protein. Furthermore, the exact subunit composition of G protein heterotrimers may depend upon regulated expression of different subunit isoforms or upon cellular processing of alpha subunits. PMID- 7876174 TI - Conditional lethality of null mutations in RTH1 that encodes the yeast counterpart of a mammalian 5'- to 3'-exonuclease required for lagging strand DNA synthesis in reconstituted systems. AB - A 5'- to 3'-exonuclease of about 45 kDa has been purified from various mammalian sources and shown to be required for the completion of lagging strand synthesis in reconstituted DNA replication systems. RTH1 encodes the yeast Saccharomyces cerevisiae counterpart of the mammalian enzyme. To determine the in vivo biological role of RTH1-encoded 5'- to 3'-exonuclease, we have examined the effects of an rth1 delta mutation on various cellular processes. rth1 delta mutants grow poorly at 30 degrees C, and a cessation in growth occurs upon transfer of the mutant to 37 degrees C. At the restrictive temperature, the rth1 delta mutant exhibits a terminal cell cycle morphology similar to that of mutants defective in DNA replication, and levels of spontaneous mitotic recombination are elevated in the rth1 delta mutant even at the permissive temperature. The rth1 delta mutation does not affect UV or gamma-ray sensitivity but enhances sensitivity to the alkylating agent methyl methanesulfonate. The role of RTH1 in DNA replication and in repair of alkylation damage is discussed. PMID- 7876175 TI - Methylation at CpG sequences does not influence histone H1 binding to a nucleosome including a Xenopus borealis 5 S rRNA gene. AB - We demonstrate that methylation of the 12 dinucleotide CpGs within a GC-rich DNA fragment containing a Xenopus borealis 5 S rRNA gene does not influence histone H1 binding to naked or nucleosomal 5 S DNA. Thus a simple mechanism in which histone H1 selectively associates with nucleosomes containing methylated CpG cannot explain the repressive effects of methylation on gene activity. PMID- 7876176 TI - Activation of mitogen-activated protein kinase by arachidonic acid in rat liver epithelial WB cells by a protein kinase C-dependent mechanism. AB - Arachidonic acid (20:4(n-6)), which is released by cells responding to a wide range of stimuli, may play an important role in intracellular signaling. We now report that incubation of WB cells with 20:4(n-6) resulted in the appearance of several tyrosine-phosphorylated cytosolic proteins. Two of the phosphotyrosine containing proteins, migrating in SDS-polyacrylamide gels of approximately 43 and 45 kDa, corresponded in mobility to phosphorylated species of the 42- and 44-kDa mitogen-activated protein kinase (MAPK) isoforms. Immunoblots of soluble fractions from unstimulated WB cells with anti-MAPK antibodies revealed the presence of the 42- and 44-kDa isoforms of MAPK. Upon incubation with 20:4(n-6), the mobility of both isoforms was retarded, consistent with their activation by phosphorylation. Chromatography of soluble fractions from these cells on Mono Q columns revealed early and late eluting peaks of myelin basic protein kinase activity, which contained the 42- and 44-kDa MAPK isoforms, respectively. Activation of MAPK was transient, peaking at 5 min, and was detectable at 5 microM 20:4(n-6). Further studies into the mechanisms by which MAPK was activated by 20:4(n-6) strongly suggested the involvement of protein kinase C (PKC). Not only did incubation of WB cells with 20:4(n-6) result in the translocation of PKC alpha, delta, and epsilon to a particulate fraction, it was found that the fatty acid failed to activate MAPK in cells pretreated for 26 h with phorbol 12 myristate 13-acetate, which depleted WB cells of PKC alpha, delta and epsilon. In addition, fatty acids of the n-3 series were effective activators of MAPK. The present study, to our knowledge, is the first to report that polyunsaturated fatty acids can cause the activation of MAPK. PMID- 7876177 TI - Ligand-dependent G protein coupling function of amyloid transmembrane precursor. AB - Amyloid precursor protein (APP), a transmembrane precursor of beta-amyloid, possesses a function whereby it associates with G(o) through its cytoplasmic His657-Lys676. Here we demonstrate that APP has a receptor function. In phospholipid vesicles consisting of baculovirally made APP695 and brain trimeric G(o), 22C11, a monoclonal antibody against the extracellular domain of APP, increased GTP gamma S binding and the turnover number of GTPase of G(o) without affecting its intrinsic GTPase activity. This effect of 22C11 was specific among various antibodies and was observed neither in G(o) vesicles nor in APP695/Gi2 vesicles. In APP695/G(o) vesicles, synthetic APP66-81, the epitope of 22C11, competitively antagonized the action of 22C11. Monoclonal antibody against APP657 676, the G(o) binding domain of APP695, specifically blocked 22C11-dependent activation of G(o). Therefore, APP has a potential receptor function whereby it specifically activates G(o) in a ligand-dependent and ligand-specific manner. PMID- 7876178 TI - The RNA polymerase I transcription factor UBF is the product of a primary response gene. AB - Transcription of the ribosomal RNA genes by RNA polymerase I is tightly coordinated with the rate of cell growth. The RNA polymerase I transcription factor, UBF, activates transcription by binding to elements within the promoter and enhancer elements within the intergenic spacer but is not required for basal transcription. To assess the role of UBF in modulating ribosomal DNA transcription, we studied its expression in NIH3T6 fibroblasts when transcription was repressed in response to serum starvation and stimulated following refeeding. Our results demonstrate a correlation between the amounts of UBF protein and the rates of ribosomal DNA transcription in quiescent and serum-stimulated cells. Nuclear run-on assays and Northern blot analyses demonstrated that the UBF gene was a primary response gene, exhibiting characteristics similar to those of c-myc and SRF. These results suggest that the regulation of transcription of the UBF gene by polymerase II represents a pathway by which cells modulate transcription by RNA polymerase I. PMID- 7876179 TI - Lysosomal hydrolases are present in melanosomes and are elevated in melanizing cells. AB - Melanosomes, the subcellular site of melanin synthesis and deposition, may be related to the endolysosomal lineage of organelles. To determine if melanosomes contain lysosomal hydrolases, we examined the subcellular distribution of five of these enzymes in melanocytes cultured from C57BL/6J mice. Analyses of Percoll gradient density centrifugations demonstrated that beta-hexosaminidase, beta galactosidase, beta-glucuronidase, and cathepsins B and L all co-sedimented with tyrosinase-rich densely sedimenting melanosomes. The melanosomal distribution of these enzymes was confirmed in studies of melanocytes cultured from albino mice and of melanocytes rendered amelanotic by transfection with the v-rasHa oncogene (which lack dense, melanized melanosomes). In these cells, only a less dense peak of activity for each hydrolase was present. The level of each hydrolase was elevated in black cells when compared with albino cells. Metabolic labeling studies confirmed that the increase in beta-glucuronidase in black versus albino cells resulted mainly from increased synthesis of this enzyme. The data suggest that melanosomes represent specialized lysosomes present within melanocytes, that they contain a broad array of lysosomal hydrolases, and that the levels of these hydrolases are elevated in cells actively engaged in pigment production. PMID- 7876180 TI - Defective export of a periplasmic enzyme disrupts regulation of fatty acid synthesis. AB - Escherichia coli thioesterase I (TesA) encoded by the tesA gene is located in the cellular periplasm. The tesA gene was modified by deletion of the leader sequence such that the mature enzyme was instead localized to the cellular cytosol. Production of thioesterase I in the cytosol results in striking changes in the pattern of E. coli lipid synthesis. In contrast to normal E. coli cells, cells producing cytosolic TesA synthesize large amounts of free fatty acid at all stages of growth. Moreover, cultures of the cytosolic TesA-producing strain continue lipid synthesis (as free fatty acid) in stationary phase whereas lipid synthesis is normally strongly inhibited in such cultures. Surprisingly, production of cytosolic thioesterase I gave only modest inhibition of membrane phospholipid synthesis. These results demonstrate that internalization of a normally secreted enzyme can disrupt normal cellular regulatory mechanisms. PMID- 7876181 TI - Embryonic chicken skeletal muscle cells fail to develop normal excitation contraction coupling in the absence of the alpha ryanodine receptor. Implications for a two-ryanodine receptor system. AB - Two ryanodine receptor (RyR), sarcoplasmic reticulum Ca2+ release channels, alpha and beta, co-exist in chicken skeletal muscles. To investigate a two-RyR Ca2+ release system, we compared electrically evoked Ca2+ transients in Crooked Neck Dwarf (cn/cn) cultured muscle cells, which do not make alpha RyR, and normal (+/?) cells. At day 3 in culture, Ca2+ release in +/? cells required extracellular Ca2+ (Ca2+o), and Ca2+ transients had slow kinetics. At day 5, Ca2+ release was Ca2+o-independent in 40% of the cells, and transients were more rapid. By day 7, all +/? cells had Ca2+o-independent Ca2+ release. Contractions were observed in +/? cells on all days. Ca2+ transients were observed in cn/cn cells on days 3, 5, and 7, but in each case they were Ca2+o-dependent and exhibited slow kinetics. Localized vesiculations, not contractions, occurred in cn/cn cells. By day 10, Ca2+ transients were no longer observed in cn/cn cells even in Ca2+o. Sarcoplasmic reticulum Ca2+ was not depleted, as caffeine induced Ca2+ transients. Thus, in the absence of alpha RyR there is a failure to develop Ca2+o-independent Ca2+ release and contractions and to sustain Ca2+o-dependent release. Moreover, contributions by the alpha RyR cannot be duplicated by the beta RyR alone. PMID- 7876182 TI - L-type voltage-sensitive Ca2+ channel activation regulates c-fos transcription at multiple levels. AB - A mechanism by which voltage-sensitive Ca2+ channel (VSCC) activation triggers c fos transcription has been characterized. Ca2+ influx through VSCCs stimulates phosphorylation of the transcription factor cAMP response element-binding protein (CREB) on serine 133 leading to an increase in the formation of transcription complexes that can elongate through a transcription pause site within the c-fos gene. Ca(2+)-stimulated CREB serine 133 phosphorylation is mediated by a Ca(2+) activated kinase and is not dependent on the cAMP-dependent protein kinase (PKA). While necessary for c-fos transcriptional induction following VSCC opening, CREB serine 133 phosphorylation is not sufficient for transcriptional activation. A second, PKA-dependent event is required. Following induction, c-fos transcription is rapidly down-regulated. Dephosphorylation of CREB serine 133 parallels and likely mediates the transcriptional shut-off event. These results suggest that the phosphorylation and dephosphorylation of CREB controls its ability to regulate transcription in membrane-depolarized cells and that multiple pathways contribute to Ca(2+)-activated gene expression. PMID- 7876183 TI - The Drosophila insulin receptor contains a novel carboxyl-terminal extension likely to play an important role in signal transduction. AB - The nucleic acid and deduced amino acid sequence of the Drosophila insulin receptor homologue (dir) has been determined. The coding sequence of dir is contained within 10 exons spanning less than 8 kilobase pairs of genomic DNA. The deduced amino acid sequence of the dir encodes a protein of 2148 amino acids, larger than the human insulin receptor due to amino- and carboxyl-terminal extensions. The overall level of amino acid identity between the DIR and human insulin and insulin-like growth factor-I receptors is 32.5 and 33.3%, respectively. Higher levels of identity are found in exon 2 (45 and 43%, respectively) and in the beta subunit (50 and 48%, respectively), and the positions of most cysteine residues in the alpha subunit cysteine-rich domain are conserved. A novel, 400-amino acid, carboxyl-terminal extension contains 9 tyrosine residues, four of which are present in YXXM or YXXL motifs, suggesting that they function as binding sites for SH2 domain-containing signaling proteins. The presence of multiple putative SH2 domain binding sites in the DIR represents a significant difference from its mammalian homologues and suggests that, unlike the human insulin and insulin-like growth factor-I receptors, the DIR forms stable complexes with signaling molecules as part of its signal transduction mechanism. PMID- 7876184 TI - Influence of intramembrane electric charge on Na,K-ATPase. AB - Effects of lipophilic ions, tetraphenylphosphonium (TPP+) and tetraphenylboron (TPB-), on interactions of Na+ and K+ with Na,K-ATPase were studied with membrane bound enzyme from bovine brain, pig kidney, and shark rectal gland. Na+ and K+ interactions with the inward-facing binding sites, monitored by eosin fluorescence and phosphorylation, were not influenced by lipophilic ions. Phosphoenzyme interactions with extracellular cations were evaluated through K(+) , ADP-, and Na(+)-dependent dephosphorylation. TPP+ decreased: 1) the rate of transition of ADP-insensitive to ADP-sensitive phosphoenzyme, 2) the K+ affinity and the rate coefficient for dephosphorylation of the K-sensitive phosphoenzyme, 3) the Na+ affinity and the rate coefficient for Na(+)-dependent dephosphorylation. Pre-steady state phosphorylation experiments indicate that the subsequent occlusion of extracellular cations was prevented by TPP+. TPB- had opposite effects. Effects of lipophilic ions on the transition between phosphoenzymes were significantly diminished when Na+ was replaced by N-methyl-D glucamine or Tris+, but were unaffected by the replacement of Cl- by other anions. Lipophilic ions affected Na-ATPase, Na,K-ATPase, and p nitrophenylphosphatase activities in accordance with their effects on the partial reactions. Effects of lipophilic ions appear to be due to their charge indicating that Na+ and K+ access to their extracellular binding sites is modified by the intramembrane electric field. PMID- 7876185 TI - Expression and purification of two isozymes of clavaminate synthase and initial characterization of the iron binding site. General error analysis in polymerase chain reaction amplification. AB - Clavaminate synthase is an Fe(2+)-, O2-, and alpha-ketoglutarate-dependent oxygenase that catalyzes three transformations in the biosynthesis of the important beta-lactamase inhibitor clavulanic acid. The genes from Streptomyces clavuligerus encoding two isoenzymes of clavaminate synthase have been over expressed in Escherichia coli to give soluble proteins whose reactions, kinetic properties, and molecular masses are in excellent agreement with the wild-type isozymes. Preliminary investigation of the active site of clavaminate synthase was undertaken using diethyl pyrocarbonate and N-ethylmaleimide. Each was inhibitory to catalytic activity. Protection from inactivation in the presence of these reagents by Fe2+, O2, and alpha-ketoglutaric acid was thwarted by the rapid self-inactivation of the enzyme in the absence of substrate. However, protection was achieved when Co2+, a potent competitive inhibitor of clavaminate synthase 2 with respect to Fe2+, was substituted. This is consistent with the presence of histidine and cysteine, respectively, at or near the active site and possibly involved in iron binding. In the course of constructing the expression vector, a simply applied general error analysis of the polymerase chain reaction was formulated to calculate the proportion of correctly replicated DNA and guide the design of experiments using this method. PMID- 7876186 TI - Effects of overall oxidation state on infrared spectra of heme a3 cyanide in bovine heart cytochrome c oxidase. Evidence of novel mechanistic roles for CuB. AB - Effects of changes in oxidation state at the other metal centers on oxidized heme a3 cyanide of bovine heart cytochrome c oxidase have been investigated. Only one CN- binds, giving Fe3+a3CN, in fully-oxidized cytochrome c oxidase and its 1-, 2 , and 3-electron reduction products. Soret/visible spectra for the heme a3 cyanide are independent of overall redox level, whereas distinct shifts in C-N infrared stretch band frequency occur upon reduction, reflecting changes in the polarity of the ligand (CN-) environment. Catalysis of O2 reduction can be critically dependent upon such changes in polarity at the reduction site. These findings indicate that CuB, when reduced, exists in two forms whose relative stabilities are independent of Fea and CuA oxidation states and, when oxidized, is in only one stable form. These results are consistent with the oxidation of Cu+B triggering proton pumping and with the involvement of a CuB ligand in respiratory control. Electron equivalents introduced into the enzyme are distributed equally among Fea, CuA, and CuB, which raises the possibility that all four electrons used in O2 reduction are donated via Cu+B, which is favorably positioned with respect to Fea3 (the O2 binding site) in order to carry out this role in electron transfers. PMID- 7876187 TI - Effect of LpA-I composition and structure on cholesterol transfer between lipoproteins. AB - The effect of high density lipoprotein composition on the rates of unesterified cholesterol exchange between low density lipoproteins (LDL) and well-defined homogeneous discoidal lipoproteins (LpA-I) reconstituted with phosphatidylcholine, cholesterol, and apolipoprotein A-I (apoA-I) has been investigated. LpA-I containing cholesterol and 2, 3, and 4 apoA-I molecules per particle differed in their ability to accept or donate cholesterol. A significant cholesterol exchange occurs between LDL and Lp2A-I (7.8 and 9.6 nm), while there is little or no cholesterol exchange detectable between LDL and Lp3A-I (10.8 and 13.4 nm) and Lp4A-I (17.0 nm) complexes. The cholesterol transfer from LDL to the cholesterol-free Lp2A-I (9.6 nm), Lp3A-I (13.4 nm), and Lp4A-I (17.0 nm) particles also shows significant cholesterol transfer to Lp2A-I, while there is no detectable transfer to Lp3- and 4A-I particles. The rates of cholesterol transfer to cholesterol-free and cholesterol-containing Lp2A-I appear to differ significantly. Cholesterol transfer from LDL to cholesterol-free Lp2A-I is zero order with respect to acceptor concentrations when the Lp2A-I/LDL ratio is above 10. Transfer rates from LDL to cholesterol-free Lp2A-I are faster for the smaller Lp2A-I (8.5 nm) than to the larger Lp2A-I (9.7 nm) and exhibit half-times (t1/2) at 25 degrees C of 4.0 and 5.3 h, respectively. In contrast, cholesterol transfer from LDL to cholesterol-containing Lp2A-I remains dependent upon acceptor concentrations to an acceptor/donor particle ratio of 80. In addition, transfer from LDL to cholesterol-containing Lp2A-I is faster to the 9.6 nm than to 7.8 nm particles, with t1/2 of 1.4 and 2.3 h, respectively. The rates of cholesterol transfer from Lp2A-I to LDL are higher than in the opposite direction, in particular for the small Lp2A-I (7.8 nm), which has a t1/2 of approximately 50 min. The results show that changes in the composition and structure of apoA-I containing particles have a significant effect on inter-lipoprotein exchange of cholesterol. This suggests that the kinetics of cholesterol transfer to and from reconstituted discoidal LpA-I particles cannot be fully explained by passive aqueous diffusion. PMID- 7876188 TI - Isolation of a protein complex containing translation initiation factor Prt1 from Saccharomyces cerevisiae. AB - Translation initiation factor Prt1 was purified from a ribosomal salt wash fraction of Saccharomyces cerevisiae cells by ammonium sulfate precipitation, DEAE chromatography, phosphocellulose chromatography, sucrose density gradient centrifugation, and non-denaturing polyacrylamide gel electrophoresis. Prt1 protein cofractionates with four other polypeptides during all steps of purification suggesting that it is part of a protein complex containing polypeptide subunits with apparent molecular masses of 130, 80, 75 (Prt1), 40, and 32 kDa. Deletion of the first AUG codon in the published sequence of the PRT1 gene results in the synthesis of functional Prt1 protein indicating that the actual molecular mass of the Prt1 subunit is 82.7 kDa. This is in agreement with results from primer extension experiments reported earlier by Keierleber et al. (Keierleber, C., Wittekind, M., Qin, S., and McLaughlin, C. S. (1986) Mol. Cell. Biol. 6, 4419-4424). The Prt1-containing protein complex is an active translation factor as shown by its ability to restore translation in a cell-free system derived from a temperature-sensitive prt1 mutant strain in which endogenous Prt1 activity is inactivated by heating the extract to 37 degrees C. The question of whether the Prt1-containing protein complex represents the yeast homologue of mammalian translation initiation factor eIF-3 is discussed. PMID- 7876189 TI - Spectroscopic evidence for a common electron transfer pathway for two tryptophan tryptophylquinone enzymes. AB - Aromatic amine dehydrogenase (AADH) and methylamine dehydrogenase (MADH) are the only two enzymes known to use the cofactor tryptophan tryptophylquinone (TTQ). Each catalyzes oxidative deamination of a distinct class of primary amines. A detailed comparison of their circular dichroic spectra indicates that both proteins share a similar fold with their TTQ cofactors residing in similar environments and that this may be a useful diagnostic probe for TTQ enzymes. Alcaligenes faecalis cells induced to express AADH also express a large amount of the blue copper protein, azurin. Oxidized azurin is rapidly reduced by a catalytic amount of AADH in the presence of the substrate, tyramine. Three A. faecalis cytochromes-c and three other cytochromes-c were tested for electron transfer activity with AADH. Azurin markedly facilitated electron transfer from AADH to each cytochrome. This suggests that AADH and azurin may form an electron transfer complex with a c-type cytochrome, analogous to the crystallographically determined MADH-amicyanin-cytochrome c-551i complex (Chen, L., Durley, R. C. E., Matthews, F. S., and Davidson, V. L. (1994) Science 264, 86-90). The similarities of MADH and AADH plus the demonstration of azurin and multiple cytochromes as functional electron-transfer partners suggest that both TTQ-bearing enzymes share common mechanisms for oxidative deamination and subsequent electron transfer. PMID- 7876190 TI - Characterization of a GC-rich region containing Sp1 binding site(s) as a constitutive responsive element of the alpha 2(I) collagen gene in human fibroblasts. AB - To analyze regulatory elements in the human alpha 2(I) collagen gene (COL1A2) promoter, a series of deletion mutants from -323 to -186 base pairs was tested in transient transfection assays in human fibroblasts. A strong positive responsive element was mapped to a GC-rich region located between base pairs -303 and -271. This region contains three binding sites (GC-boxes) resembling recognition sites for the transcription factor Sp1. Substitution mutations in the GC-boxes abolished binding to the GC-rich region in gel shift analyses and resulted in 90% reduction of promoter activity in transient transfection assays. We demonstrated that transcription factor Sp1 is essential for binding based on the following observations. 1) Sp1 consensus binding site alone competes by binding to the GC rich region in the DNase I protection assay; 2) both Sp1 consensus binding site and Sp1 antibodies prevent the formation of a DNA-protein complex in the mobility shift assay; 3) anti-Sp1 antibodies recognize a component of the complex competed for by Sp1 consensus binding site. PMID- 7876191 TI - Genomic structure and expression of the ADH7 gene encoding human class IV alcohol dehydrogenase, the form most efficient for retinol metabolism in vitro. AB - Human alcohol dehydrogenase (ADH) consists of a family of five evolutionarily related classes of enzymes that collectively function in the metabolism of a wide variety of alcohols including ethanol and retinol. Class IV ADH has been found to be the most active as a retinol dehydrogenase, thus it may participate in retinoic acid synthesis. The gene encoding class IV ADH (ADH7) has now been cloned and subjected to molecular examination. Southern blot analysis indicated that class IV ADH is encoded by a single unique gene and has no related pseudogenes. The class IV ADH gene is divided into nine exons, consistent with the highly conserved intron/exon structure of other mammalian ADH genes. The predicted amino acid sequence of the exon coding regions indicates that a protein of 373 amino acids, excluding the amino-terminal methionine, would be translated, sharing greater sequence identity with class I ADH (69%) than with classes II, III or V (59-61%). Expression of class IV ADH mRNA was detected in human stomach but not liver. This correlates with previous protein studies, which have indicated that class IV ADH is the major stomach ADH but unlike other ADHs is absent from liver. Primer extension studies using human stomach RNA were performed to identify the transcription initiation site lying 100 base pairs upstream of the ATG translation start codon. Nucleotide sequence analysis of the promoter region indicated the absence of a TATA box sequence often located about 25 base pairs upstream of the start site as well as the absence of GC boxes, which are quite often seen in promoters lacking a TATA box. The class IV ADH promoter thus differs from the other ADH promoters, which contain either a TATA box (classes I and II) or GC-boxes (class III), suggesting a fundamentally different form of transcriptional regulation. PMID- 7876192 TI - Cloning and expression of four novel isoforms of human interleukin-1 beta converting enzyme with different apoptotic activities. AB - To understand the mechanism of interleukin-1 beta converting enzyme (ICE) activation in apoptosis, we analyzed the expression of ICE mRNA in two human cell lines by reverse transcription-polymerase chain reaction technique. This resulted in the identification and cloning of four alternatively spliced ICE mRNA isoforms. Although all the alternative splicing events were within the coding sequence of ICE, the four ICE isoforms maintained open reading frames and were designated as ICE beta, gamma, delta, and epsilon. In ICE gamma, most of the propeptide (amino acids 20-112) is deleted, which suggests that it may function as a catalyst for ICE autoprocessing in vivo. In ICE delta, amino acids 288-335, which contain the cleavage sites between the p20 and p10 subunits of ICE, are deleted thus resulting in its inactivation. Intriguingly, in ICE epsilon amino acids 20-335, which encompass most of the propeptide and the p20 subunit, are deleted resulting in the formation of a molecule that is homologous to the p10 subunit. Examination of the ability of these four ICE isoforms to cause apoptosis revealed that only the parental ICE alpha and isoforms beta and gamma, but not isoforms delta and epsilon, can induce apoptosis when overexpressed in Sf9 insect cells. In addition, coexpression of the p20 and p10 but not the p20 and ICE epsilon in Sf9 cells results in apoptosis. Interestingly, expression of ICE epsilon and to a lesser degree ICE delta resulted in extension of the survival of baculovirus-infected cells in a manner similar to expression of BCL2. The ability of ICE epsilon to extend the survival of Sf9 cells suggests that baculovirus induced apoptosis in these cells is mediated by an ICE-like protease. We show that ICE epsilon can bind to the p20 subunit of ICE and potentially may compete with the p10 subunit to form an inactive ICE complex. Therefore, by acting as a dominant inhibitor of ICE activity, ICE epsilon may regulate ICE activation in vivo. PMID- 7876193 TI - Endogenous cleavage of phospholipase C-beta 3 by agonist-induced activation of calpain in human platelets. AB - Two membrane-associated phosphoinositide-specific phospholipase Cs (mPI-PLC-1 and mPI-PLC-2) and a cytosolic enzyme (cPI-PLC) that were activated by brain G protein beta gamma subunits have been isolated from human platelets. The truncation of mPI-PLC-1 that was mediated by mu-calpain induced much higher activation by beta gamma subunits (Banno, Y., Asano, T., and Nozawa, Y. (1994) FEBS Lett. 340, 185-188). On the basis of size and immunological cross reactivity, mPI-PLC-1 (155 kDa) was PLC-beta 3, and mPI-PLC-2 (100 kDa) was its truncated form. The cPI-PLC (140 kDa) was recognized by the antibody selective for internal sequences of PLC-beta 3 but not by the antibody raised against its carboxyl terminus, indicating that it may be related to PLC-beta 3. Treatment of human platelets with A23187 and dibucaine, activators of calpain, caused cleavage of actin-binding protein and talin in a time-dependent manner. At the same time, decrease of PLC-beta 3 (155 and 140 kDa) and concomitant increase of the 100-kDa product of cleavage were observed on immunoblots with the antibody to internal sequences of PLC-beta 3. Furthermore, stimulation of platelets by natural agonists, thrombin and collagen, caused the cleavage of PLC-beta 3 (155 and 140 kDa) and an increase of 100 kDa PLC-beta 3 in a time- and dose-dependent manner. The cleavage of these PLC-beta 3 enzymes was completely blocked by calpain inhibitor, calpeptin, indicating that the PLC-beta 3 modification may be a consequence of platelet activation leading to activation of calpain. This is the first demonstration that PLC-beta 3 is indeed cleaved by calpain upon platelet activation by physiological agonists. The cleavage of PLC-beta 3 evoked by thrombin and collagen but not ADP was correlated with irreversible aggregation, suggesting that the PLC-beta 3 modification may play a role in secondary irreversible aggregation in agonist-stimulated human platelets. PMID- 7876194 TI - Endocytosis and lysosomal targeting of epidermal growth factor receptors are mediated by distinct sequences independent of the tyrosine kinase domain. AB - Ligand-induced internalization of the epidermal growth factor receptor (EGFR) leads to accelerated receptor degradation. Two models have been proposed to explain this. In the first model, induced internalization expands the intracellular pool of receptors, leading to enhanced lysosomal targeting. The second model proposes that activation of intrinsic receptor kinase activity induces inward vesiculation of endosomes, thus interrupting receptor recycling. To test these models, we created EGFR mutants that lack the conserved tyrosine kinase domain, but retain different parts of the distal carboxyl terminus regulatory region. Mutants lacking all distal regulatory sequences underwent slow internalization (0.02 min-1) and turnover (t1/2 approximately 24 h), similar to unoccupied, holo-EGFR. Mutant receptors that lacked the kinase domain, but retained the entire distal regulatory domain, were constitutively internalized and targeted to lysosomes, even in the absence of EGF. The turnover of these receptors (t1/2 approximately 11 h) was similar to that of occupied, kinase active holo-EGFR (t1/2 approximately 9.5 h). These results show that receptor tyrosine kinase activity is not required for the targeting of EGFR to lysosomes. Receptor mutants which expressed previously identified endocytic sequences underwent rapid internalization. Unexpectedly, enhanced turnover of EGFR mutants required additional sequences located between residues 945 and 991 in the holo EGFR. Thus, internalization and lysosomal targeting of EGFR are separate processes mediated by distinct sequences. Our results indicate that induced internalization is necessary, but not sufficient, for enhanced EGFR degradation. Instead, down-regulation requires exposure of previously cryptic internalization and lysosomal targeting sequences. Occupied EGFR thus appear to be handled by the endocytic machinery in the same fashion as other constitutively internalized or lysosomally targeted receptors. PMID- 7876195 TI - Intracellular trafficking of epidermal growth factor family ligands is directly influenced by the pH sensitivity of the receptor/ligand interaction. AB - Using members of the epidermal growth factor (EGF) family as well as site directed recombinant human EGF mutants, we investigated how ligand binding properties influence endosomal sorting. Mouse EGF (mEGF), human EGF (hEGF), and transforming growth factor alpha (TGF alpha) bind to the human EGF receptor (EGFR) with similar affinities at pH 7.4. However, the binding properties of these ligands have substantially different pH sensitivities resulting in varying degrees of dissociation from the receptors at lower pH levels characteristic of endosomes. We employed a steady-state sorting assay to determine the fraction of ligand sorted to recycling versus degradation as a function of the number of intracellular ligand molecules in mouse B82 fibroblasts. mEGF, hEGF, and TGF alpha display significantly different steady-state endosomal sorting patterns which correspond to the extent of their dissociation at endosomal pH. Moreover, several recombinant hEGF mutants with differing affinities exhibit altered endosomal sorting compared to hEGF, demonstrating a similar direct relationship between ligand binding properties and endosomal sorting outcomes. Intracellular trafficking of the EGF ligands was also monitored by measuring the observed degradation rate constants. These likewise show marked differences that correlate with the differing pH sensitivities of the ligands' binding properties. PMID- 7876196 TI - Regulation of rat ornithine decarboxylase promoter activity by binding of transcription factor Sp1. AB - Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine biosynthesis. We investigated the transcriptional regulation of the rat ODC gene using transient expression assays. The 5'-flanking region (-1156 to +13) of the ODC gene was sufficient to mediate strong basal expression of a luciferase reporter. Sequences between -345 and -93 contributed to basal promoter activity. This region, containing five potential Sp1 binding sites, was analyzed by electrophoretic mobility shift assays. Three specific DNA-protein complexes were identified using H35 nuclear extracts and the -345/-93 ODC probe. Binding to all three was eliminated by competition with an oligonucleotide containing an Sp1 binding site, but not by a mutant Sp1 oligonucleotide. Preincubation with an antibody against Sp1 supershifted complexes associated with one or more of Sp1 binding sites 1-4 as well as with site 5. DNase I footprinting revealed two protected regions: PR-I (-92 to -130) and PR-II (-304 to -332). PR-I contains a putative binding site for Sp1 that was protected by recombinant Sp1 protein. Transfection studies in Schneider SL2 cells demonstrated that the ODC promoter is transactivated up to 350-fold by Sp1 and that this transactivation is dependent on the presence of Sp1 binding sites 1-4. Thus, although the ODC promoter binds multiple nuclear proteins, Sp1 or a related protein appears to be a critical determinant of ODC transcription, possibly through cooperative interactions between Sp1 and additional transcription factors. PMID- 7876197 TI - Two trans-acting metalloregulatory proteins controlling expression of the copper ATPases of Enterococcus hirae. AB - Enterococcus hirae possesses two P-type ATPases, CopA and CopB, that are involved in copper homeostasis. These enzymes are induced by extracellular copper concentrations that are either too low or too high for optimal growth. To identify the regulatory proteins involved in induction, the DNA upstream of copA was cloned and sequenced. Following a putative promoter region, it contains two genes, copY and copZ, that encode proteins of 145 and 69 amino acids, respectively. Both proteins contain metal binding motifs and exhibit significant sequence similarity to known regulatory proteins. Gene disruption of copY by reverse genetics caused constitutive overexpression of CopA and CopB, generating a copper-dependent phenotype. In contrast, disruption of copZ suppressed the expression of the two copper-ATPases, rendering the cells copper-sensitive. Both null mutations could be complemented in trans with plasmids bearing copY or copZ. Thus, copY and copZ encode trans-acting metalloregulatory proteins that are required for induction of the cop operon by copper. In this mechanism, CopY apparently acts as a metal-fist type repressor and CopZ as an activator. PMID- 7876198 TI - Changes in superhelicity are introduced into closed circular DNA by binding of high mobility group protein I/Y. AB - Mammalian high mobility group HMG-I/Y chromatin proteins bind to the minor groove of A.T-rich DNA sequences with high affinity both in vivo and in vitro. Topoisomerase I-mediated relaxation assays, analyzed by one- and two-dimensional agarose gel electrophoresis, indicate that binding of recombinant human HMG-I/Y to closed circular DNA introduces positive supercoils at low protein to nucleotide molar ratios and negative supercoils at higher ratios. This is interpreted to mean that HMG-I/Y binding initially causes bending of the DNA helix followed by unwinding of the helix. In contrast, binding of another minor groove binding ligand, netropsin, introduces positive supercoils only. An in vitro produced mutant HMG-I/Y protein lacking the negatively charged carboxyl terminal domain binds A.T-rich DNA approximately 1.4-fold better than the native protein, yet it is estimated to be 8-10-fold more effective at introducing negative supercoils. This finding suggests that the highly acidic C-terminal region of the HMG-I/Y protein may function as a regulatory domain influencing the amount of topological change induced in DNA substrates by binding of the protein. Footprinting of HMG-I/Y on negatively supercoiled A.T-rich DNA using diethylpyrocarbonate suggests that the protein is able to recognize, bind to, and alter the conformation of non-B-form DNA. PMID- 7876199 TI - Variable stoichiometric efficiency of Ca2+ and Sr2+ transport by the sarcoplasmic reticulum ATPase. AB - In comparative experiments with Ca2+ ATPase in native sarcoplasmic reticulum vesicles and reconstituted proteoliposomes, we find that a variable stoichiometry of Ca2+ or Sr2+ transport per ATPase cycle is observed in the absence of passive leak through independent channels. The observed ratio is commonly lower than the optimal value of 2 and depends on the composition of the reaction mixture. In all cases, a progressive rise in the lumenal concentration of Ca2+ and Sr2+ is accompanied by a parallel reduction of coupling ratios. Significant ATPase activity remains even after asymptotic levels of Ca2+ accumulation are reached. This residual activity subsides if the Ca2+ concentration in the outer medium is reduced below activating levels (as it would following Ca2+ transients in muscle fibers). The reduction of stoichiometric coupling is explained with a reaction scheme, including a branched pathway for hydrolytic cleavage of phosphorylated intermediate before release of Ca2+ into the lumen of the vesicles. Flux through this pathway is favored when net lumenal Ca2+ dissociation from the phosphoenzyme is impeded and results in P(i) production accompanied by lumenal and medium Ca2+ exchange. Occurrence of reactions through branched pathways may have general implications for the stoichiometric efficiency of energy-transducing enzymes. PMID- 7876200 TI - The plant inorganic pyrophosphatase does not transport K+ in vacuole membrane vesicles multilabeled with fluorescent probes for H+, K+, and membrane potential. AB - It has been claimed that the inorganic pyrophosphatase (PPase) of the plant vacuolar membrane transports K+ in addition to H+ in intact vacuoles (Davies, J. M., Poole, R. J., Rea, P. A., and Sanders, D. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 11701-11705). Since this was not confirmed using the purified and reconstituted PPase consisting of a 75-kDa polypeptide (Sato, M.H., Kasahara, M., Ishii, N., Homareda, H., Matsui, H., and Yoshida, M. (1994) J. Biol. Chem. 269, 6725-6728), these authors proposed that K+ transport by the PPase is dependent on its association with other membrane components lost during purification. We have examined the hypothesis of K+ translocation by the PPase using native vacuolar membrane vesicles from Vitis vinifera suspension cells, multilabeled with fluorescent probes for K+, H+, and membrane potential. This material contained a high proportion of right-side-out, tightly sealed vesicles, exhibiting high PPase activity which was strongly stimulated by uncouplers and K+. Proton pumping occurred in response to pyrophosphate addition in the absence of K+. No K+ incorporation into the vesicles could be observed after PPase energization in the presence of K+, although H+ transport was highly stimulated. The hydrolytic activity was stimulated by a protonophore and by a H+/K+ exchanger but not by the K+ ionophore valinomycin. No evidence could be obtained supporting the operation of an endogenous K+/H+ exchanger capable to dissipate the putative active K+ flux generated by the PPase. We conclude that PPase in native vacuolar membrane vesicles does not transport K+. PMID- 7876201 TI - Analysis of the paramyosin/miniparamyosin gene. Miniparamyosin is an independently transcribed, distinct paramyosin isoform, widely distributed in invertebrates. AB - Miniparamyosin, a distinct Drosophila melanogaster paramyosin isoform of 60 kDa, is shown here to be encoded by the same gene as paramyosin. The gene, located at 66D14, spans over 12.8 kilobases (kb) and is organized into 10 exons, 9 of which code for the paramyosin transcripts. An exon, located between exons 7 and 8, codes for the 5'-end of the miniparamyosin, and the two proteins share the two last exons of the gene. Mapping of the 5'-ends of these transcripts indicates that the paramyosin and miniparamyosin mRNAs arise from two overlapping transcriptional units; the miniparamyosin transcription initiation site is located inside a paramyosin intron, 8 kb downstream of the one used for paramyosin transcription. The existence of two different promoters and the conserved and nonconserved features of their sequences suggest a very complex regulation of these two muscle proteins. In fact, while paramyosin is expressed at two distinct stages of development as most other Drosophila muscle proteins, miniparamyosin appears late in development, being present only in the adult musculature. The absence of exon 1B, the specific exon of miniparamyosin, in the nematode Caenorhabditis elegans, as well as additional lines of evidence support the lack of miniparamyosin in this particular organism. However, it is present in most invertebrate species examined, including different arthropod, annelid, mollusc, and echinoderm species. PMID- 7876202 TI - Enhancement of the endo-beta-1,4-glucanase activity of an exocellobiohydrolase by deletion of a surface loop. AB - In the commonly accepted mechanism for enzymatic hydrolysis of cellulose, endo beta-1,4-glucanases randomly cleave glucosidic bonds within glucan polymers, providing sites for attack by exo-cellobiohydrolases (EC 3.2.1.91). It has been proposed that hydrolysis by Trichoderma reesei cellobiohydrolase II is restricted to the ends of cellulose polymers because two surface loops cover its active site to form a tunnel. In a closely related endoglucanase, E2 from Thermomonospora fusca, access to the substrate appears to be relatively unhindered because the carboxyl-proximal loop is shortened, and the amino-proximal loop is displaced. The hypothesis was examined by deletion of a region in Cellulomonas fimi cellobiohydrolase A corresponding to part of the carboxyl-proximal loop of T. reesei cellobiohydrolase II. The mutation enhanced the endoglucanase activity of the enzyme on soluble O-(carboxymethyl)cellulose and altered its activities on 2',4'-dinitrophenyl-beta-D-cellobioside, insoluble cellulose, and cellotetraose. PMID- 7876204 TI - Angiotensin II stimulates tyrosine phosphorylation of the focal adhesion associated protein paxillin in aortic smooth muscle cells. AB - Treatment of vascular smooth muscle cells (SMC) with angiotensin II (AII) leads to an increase in the tyrosine phosphorylation of multiple cellular substrates. Here, we have demonstrated that AII stimulates tyrosine phosphorylation of the focal adhesion-associated protein paxillin in rat aortic SMC. AII-induced phosphorylation of paxillin was detectable within 1 min and was sustained up to 60 min. Preincubation with the AT1-selective antagonist losartan abolished this response. The stimulatory effect of AII on paxillin tyrosine phosphorylation was observed only in aortic SMC and not in other target cells such as adrenal zona glomerulosa cells, chromaffin cells, or hepatocytes. The effect of AII was dependent on the activation of phospholipase C. Chelation of intracellular calcium completely inhibited the ability of AII to stimulate paxillin tyrosine phosphorylation, while selective inhibition of protein kinase C partially attenuated the response. In contrast, treatment of the cells with pertussis toxin had no effect on AII-induced paxillin tyrosine phosphorylation. These findings identify paxillin as a new substrate for AII-stimulated tyrosine phosphorylation and suggest a role for cytoskeleton-associated proteins in the growth response of aortic SMC. PMID- 7876203 TI - The cellular C1 factor of the herpes simplex virus enhancer complex is a family of polypeptides. AB - The alpha/immediate early genes of herpes simplex virus are regulated by the specific assembly of a multiprotein enhancer complex containing the Oct-1 POU domain protein, the viral alpha-transinduction factor alpha TIF, (VP16, ICP25), and the C1 cellular factor. The C1 factor from mammalian cells is a heterogeneous but related set of polypeptides that interact directly with the alpha transinduction factor to form a heteromeric protein complex. The isolation of cDNAs encoding the polypeptides of the C1 factor suggests that these proteins are proteolytic products of a novel precursor. The sequence of the amino termini of these polypeptide products indicate that the proteins are generated by site specific cleavages within a reiterated 20-amino acid sequence. Although the C1 factor appears to be ubiquitously expressed, it is localized to subnuclear structures in specific cell types. PMID- 7876205 TI - The 30-kDa protein binding to the "initiator" of the baculovirus polyhedrin promoter also binds specifically to the coding strand. AB - We previously reported the purification and characterization of the polyhedrin promoter-binding protein (PPBP), an unusual DNA-binding protein that interacts with transcriptionally important motifs of the baculovirus polyhedrin gene promoter (S. Burma, B. Mukherjee, A. Jain, S. Habib, and S.E. Hasnain, J. Biol. Chem. (1994) 269, 2750-2757. PPBP also exhibits a sequence-specific single stranded DNA-binding activity. Gel retardations and competition analyses with double- and single-stranded oligonucleotides indicated that PPBP binds the coding strand and not the noncoding strand of the promoter. This was further confirmed by UV cross-linking and Southwestern blotting experiments. Gel retardations with mutated oligonucleotides indicated that both dsDNA and ssDNA binding involve common AATA-AATAAGTATT motifs. However, ssDNA binding is dependent upon ionic interactions unlike dsDNA binding, which is mainly through nonionic interactions. The affinity of PPBP for the coding strand appears to be higher than that for duplex promoter DNA. Interestingly, the PPBP-coding strand complex has a longer half-life (approximately 60 min) than the PPBP-duplex promoter complex (approximately 15 min). PPBP represents a unique example of an "initiator" promoter-binding protein with dual dsDNA and ssDNA binding activities, and this reconciles very well with the unusual binding characteristics displayed by it. The formation of the PPBP-coding strand complex in vivo may be a crucial step for the exceptionally high and repeated rounds of transcriptional activity of the baculovirus polyhedrin gene promoter. PMID- 7876207 TI - Occupancy of the Dictyostelium cAMP receptor, cAR1, induces a reduction in affinity which depends upon COOH-terminal serine residues. AB - Many G-protein-coupled receptors display a rapid decrease in ligand binding following pretreatment with agonist. cAR1, a cAMP receptor expressed early in the developmental program of Dictyostelium, mediates chemotaxis, activation of adenylyl cyclase, and gene expression changes that bring about the aggregation of 10(5) amoebae to form a multicellular structure. Occupancy of cAR1 by cAMP initiates multiple desensitization processes, one of which is an apparent reduction in binding sites. In transformed cells expressing cAR1 constitutively, Scatchard analyses revealed that this apparent loss of ligand binding is largely due to a significant reduction in the affinity of cAR1 for cAMP. A parallel increase in the dose dependence of cAR1-mediated cAMP uptake was observed. Consistent with these findings, proteolysis of intact cells and immunofluorescence suggested that cAR1 remains on the cell-surface following cAMP treatment. Finally, agonist-induced loss of ligand binding is impaired in cAR1 mutants lacking a cluster of cytoplasmic serine residues, which are targets of cAMP-induced phosphorylation. PMID- 7876206 TI - Adrenomedullin stimulates two signal transduction pathways, cAMP accumulation and Ca2+ mobilization, in bovine aortic endothelial cells. AB - The biological action of adrenomedullin, a novel hypotensive peptide, on bovine aortic endothelial cells, was examined. The specific binding of adrenomedullin to these cells was observed, and adrenomedullin was found to induce intracellular cAMP accumulation in a dose-dependent manner. EC50 for the cAMP accumulation was about 100 times lower than the apparent IC50 for the binding assay. Adrenomedullin also induced increase of intracellular free Ca2+ in endothelial cells in a dose-dependent manner. The Ca2+ response to adrenomedullin was biphasic with an initial transient increase due to the release from thapsigargin sensitive intracellular Ca2+ storage and a prolonged increase by influx through the ion channel on the plasma membrane. This intracellular free Ca2+ increase resulted from phospholipase C activation and inositol 1,4,5-trisphosphate formation, and seemed to cause nitric oxide synthase activation by monitoring intracellular cGMP accumulation. Both cAMP accumulation and Ca2+ increased responses to adrenomedullin were mediated by cholera toxin-sensitive G protein, but the two signal transduction pathways were independent. Thus, the results suggest that adrenomedullin elicits the hypotensive effect through at least two mechanisms, a direct action on vascular smooth muscle cells to increase intracellular cAMP and an action on endothelial cells to stimulate nitric oxide release, with both leading to vascular relaxation. PMID- 7876208 TI - Neurons can maintain multiple classes of nicotinic acetylcholine receptors distinguished by different subunit compositions. AB - Although 10 genes have been cloned encoding putative subunits of neuronal nicotinic acetylcholine receptors, little is known about the variety or subunit composition of such receptors expressed by individual neurons. Chick ciliary ganglion neurons express five of the known genes and assemble a class of synaptic type receptors collectively containing gene products from three of them: alpha 3, beta 4, and alpha 5. Using subunit-specific monoclonal antibodies, we show here that all of the synaptic-type acetylcholine receptors having alpha 3 also have beta 4 subunits and vice versa. In addition, most, if not all, of the alpha 5 gene product present in fully assembled receptors is associated with both alpha 3 and beta 4 subunits. Although the receptors may be homogeneous in these respects, only about 20% of them also contain the fourth gene product, beta 2, newly identified in the ganglion; essentially all of the neurons express the beta 2 gene. No beta 2 subunits are found coassembled with the fifth acetylcholine receptor gene product expressed by the neurons, alpha 7, which has been shown previously to comprise a class of abundant, nonsynaptic receptors on the cells. The identification of three acetylcholine receptor subtypes distinguished by subunit composition on the same neurons provokes questions about their individual physiological roles. PMID- 7876209 TI - Characteristics of NIFNE in Azotobacter vinelandii strains. Implications for the synthesis of the iron-molybdenum cofactor of dinitrogenase. AB - The products of the nifN and nifE genes of Azotobacter vinelandii function as a 200-kDa alpha 2 beta 2 tetramer (NIFNE) in the synthesis of the iron-molybdenum cofactor (FeMo-co) of nitrogenase, the enzyme system required for biological nitrogen fixation. NIFNE was purified using a modification of the published protocol. Immunoblot analysis of anoxic native gels indicated that distinct forms of NIFNE accumulate in strains deficient in either NIFB (delta nifB::kan delta nifDK) or NIFH (delta nifHDK). During the purification of NIFNE from the delta nifHDK mutant, its mobility in these gels changed, becoming similar to that of NIFNE from the delta nifB::kan delta nifDK mutant. While NIFB activity initially co-purified with the NIFNE activity from the delta nifHDK mutant, further purification of NIFNE activity resulted in the loss of the co-purifying NIFB activity; this loss correlated with the change in NIFNE mobility on native gels. These results suggest that the form of NIFNE accumulated in the delta nifHDK mutant is associated with NIFB activity in crude extract but loses this association during NIFNE purification. Addition of the purified metabolic product of NIFB, termed NifB-co, to either NIFNE purified from the delta nifHDK strain or to the NIFNE in crude extract of the delta nifB::kan delta nifDK strain caused a change in the mobility of NIFNE on anoxic native gels to that of the form accumulated in a delta nifHDK mutant. These results support a model where both NifB-co and dinitrogenase reductase participate in FeMo-co synthesis through NIFNE, which serves as a scaffold for this process. PMID- 7876210 TI - The role of Barbie box sequences as cis-acting elements involved in the barbiturate-mediated induction of cytochromes P450BM-1 and P450BM-3 in Bacillus megaterium. AB - In a previous publication (He, J.-S., and Fulco, A. J. (1991) J. Biol. Chem. 266, 7864-7869), we reported that a 15-17-base pair DNA sequence (designated a Barbie box element) in the 5'-regulatory regions of cytochrome P450BM-1 and P450BM-3 genes from Bacillus megaterium was recognized by a barbiturate-regulated protein. It is now recognized that essentially all eukaryotic and prokaryotic genes whose 5'-flanking regions are known and that encode barbiturate-inducible proteins contain the Barbie box element. A 4-base pair sequence (AAAG) is found in the same relative position in all Barbie box elements. In B. megaterium, mutation of the Barbie box located in the P450BM-1 gene leads to the constitutive synthesis of cytochrome P450BM-1 and a 10-fold increase of expression of Bm1P1, a small gene located upstream of the P450BM-1 gene, that encodes a putative regulatory protein. Mutation of the P450BM-3 Barbie box significantly increased the expression of both P450BM-3 and Bm3P1 (another small gene located upstream of the P450BM-3 gene that encodes a second putative regulatory protein) in response to pentobarbital induction but left the basal levels unaffected. In gel mobility shift assays, Bm3R1, a repressor of the P450BM-3 gene, was found to specifically interact with the Barbie box sequences of the B. megaterium P450 genes. Mutated Barbie boxes showed a decreased binding affinity for Bm3R1 compared to their wild type (unmutated) counterparts. Barbie box sequences were also shown to specifically interact with putative positive regulatory factors of B. megaterium cells. These putative positive factors were induced by pentobarbital and were also present at high levels during late stationary phase of B. megaterium cell cultures grown in the absence of barbiturates. The mutated Barbie box sequences had greater binding affinity for these positive factors than did unmutated Barbie box sequences. DNase I footprinting analysis of the 5'-flanking region of the P450BM-1 gene revealed that these positive factors protected a segment of DNA covering a portion of the Barbie box sequence and a small flanking region. Similar footprinting experiments with the 5'-flanking region of the P450BM-3 gene failed, however, to unambiguously reveal protected sequences in the Barbie box region. The evidence suggests that the positive factors and Bm3R1 compete with each other for binding to the Barbie box region, especially in the 5'-flanking region of the P450BM-1 gene, and for putative roles in the regulation of transcription from the B. megaterium P450 genes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7876211 TI - Shear stress-induced [Ca2+]i transients and oscillations in mouse fibroblasts are mediated by endogenously released ATP. AB - The effects of ATP, U-73122, apyrase, and saline shear stress on [Ca2+]i homeostasis were studied in fura-2 loaded, mouse fibroblast cells (L929), both in suspension and plated on glass. Release of internal Ca2+ was induced by ATP, via a receptor identified pharmacologically as a P2U type. In single cells, low concentrations of ATP evoked [Ca2+]i oscillations. These events were blocked by the putative phospholipase C inhibitor, U-73122 (but not by the inactive analog U 73343) and by the ATP/ADPase, apyrase. In addition, both these agents reduced the [Ca2+]i of unstimulated cells, especially after stirring, and blocked spontaneously occurring [Ca2+]i oscillations, which suggested an already activated state of the ATP receptor, independent from exogenous stimulations. Moreover, it was found that stirring of the cells was correlated with a steady accumulation of inositol phosphates, also blockable by apyrase, and that [Ca2+]i mobilization could be induced by puffs of saline in single cells. The transition to a Ca(2+)-free environment also provoked [Ca2+]i oscillations, most likely via the increase in ATP4- concentration. This evidence suggests that endogenous ATP is released from L fibroblasts in response to fluid shear stress, and this results in an autocrine, tonic up-regulation of the phosphoinositide signaling system and an ensuing alteration in Ca2+ homeostasis. Up until now, such a response to shear stress was believed to be unique to endothelial cells. PMID- 7876212 TI - Sequence identity and antigenic cross-reactivity of white face hornet venom allergen, also a hyaluronidase, with other proteins. AB - White face hornet (Dolichovespula maculata) venom has three known protein allergens which induce IgE response in susceptible people. They are antigen 5, phospholipase A1, and hyaluronidase, also known as Dol m 5, 1, and 2, respectively. We have cloned Dol m 2, a protein of 331 residues. When expressed in bacteria, a mixture of recombinant Dol m 2 and its fragments was obtained. The fragments were apparently generated by proteolysis of a Met-Met bond at residue 122, as they were not observed for a Dol m 2 mutant with a Leu-Met bond. Dol m 2 has 56% sequence identity with the honey bee venom allergen hyaluronidase and 27% identity with PH-20, a human sperm protein with hyaluronidase activity. A common feature of hornet venom allergens is their sequence identity with other proteins in our environment. We showed previously the sequence identity of Dol m 5 with a plant protein and a mammalian testis protein and of Dol m 1 with mammalian lipases. In BALB/c mice, Dol m 2 and bee hyaluronidase showed cross-reactivity at both antibody and T cell levels. These findings are relevant to some patients' multiple sensitivity to hornet and bee stings. PMID- 7876213 TI - The activity of an endoplasmic reticulum-localized pool of acetylcholinesterase is modulated by heat shock. AB - Primary cultures prepared from embryonic chick pectoral muscle were subjected to heat shock, and the effect on acetylcholinesterase activity in the cultures was examined. A rapid recovery in enzyme activity was observed soon after an initial heat shock-induced drop and was shown to be independent of de novo synthesis of protein, since it could occur in the presence of an inhibitor of protein synthesis. Lectin binding and sucrose gradient centrifugation studies suggested that molecular monomers and dimers found in the endoplasmic reticulum are involved in the observed recovery of acetylcholinesterase activity. Enhanced activation of a pre-existing pool of inactive enzyme was clearly not the main agent of the recovery in enzymic activity. Recovery relied principally on restoration of the activity of previously active, heat-denatured acetylcholinesterase molecules found in the endoplasmic reticulum. Possible agents involved in the recovery of enzymatic activity might be heat shock proteins acting as molecular chaperones. PMID- 7876214 TI - Requirements for transforming growth factor-beta regulation of the pro-alpha 2(I) collagen and plasminogen activator inhibitor-1 promoters. AB - Experiments were designed to clarify the role of several proteins, junB, retinoblastoma protein (RB), and the transforming growth factor-beta (TGF-beta) receptors that are potential intermediates in TGF-beta activation of the alpha 2(I) collagen promoter. Treatment of NIH-3T3 cells with TGF-beta increased the activity of a transiently transfected murine alpha 2(I) collagen promoter (nucleotides -350 to +54) fused to a luciferase reporter gene 9-fold. Cotransfection of a junB stimulated the basal activity of the alpha 2(I) collagen promoter 93-fold, respectively. Expression of antisense junB RNA attenuated the effect of TGF-beta. Simian virus 40 large T antigen, an inhibitor RB function, did not prevent TGF-beta effects on the alpha 2(I) collagen promoter. A chimeric receptor containing the extracellular domain of the colony-stimulating factor-1 receptor and the intracellular domain of the type I TGF-beta receptor enhanced alpha 2(I) collagen promoter activity 4.8-fold, whereas a similar chimera containing the type II receptor intracellular domain had much weaker effects. Similar results were obtained with a plasminogen activator inhibitor-1 promoter, previously shown to be activated by TGF-beta through AP-1 elements. We conclude that TGF-beta activates the alpha 2(I) collagen and plasminogen activator inhibitor-1 promoters in NIH-3T3 cells through junB and the type I TGF-beta receptor kinase domain. PMID- 7876215 TI - Pit-1 exhibits a unique promoter spacing requirement for activation and synergism. AB - The developmentally regulated Pit-1 transcription factor is involved in the activation of prolactin, growth hormone, and TSH beta expression. Using templates with spacing mutations to program an in vitro transcription system, the activity of a single Pit-1 proximal binding site within the rat prolactin promoter was shown to have a unique bimodal distance requirement. Transcription activity rapidly decreased with each 5-base pair (bp) addition to the spacing between the binding site and the TATA box. When positioned 20 bp upstream from its normal -36 position in the prolactin promoter, the activity of the Pit-1 binding site is reduced to basal levels. Placement of the site at a position 30 bp upstream resulted in a return of Pit-1-mediated activation. Using transient transfection assays in GH3 cells, the prime bimodal sites are also a requirement for optimum expression of chimeric prolactin-luciferase reporter constructs. Interestingly, optimal synergism of transcription in vivo by the prolactin distal enhancer, containing four Pit-1 binding sites and an estrogen-responsive element, is also sensitive to the placement of the proximal Pit-1 binding site. These data have important implications for Pit-1 activator function in pituitary cells and for general models of transcription synergism. PMID- 7876216 TI - Microtubule-independent phospholipid stimulation of cytoplasmic dynein ATPase activity. AB - In this study we report that phospholipid vesicles activate ATP hydrolysis by cytoplasmic dynein but not kinesin, consistent with reported differences in the organelle/vesicle binding of these motor proteins. Dynein activation by phospholipids was comparable with that seen in the presence of microtubules but was not sensitive to moderate salt concentrations and was independent of the net charge of the phospholipid, suggesting that the means of interaction between dynein and the lipid vesicle was not strictly ionic in nature. Based on this result, previous data that show that the interaction between dynein and vesicles is not ATP sensitive, and the concentration dependence observed for lipid activation of cytoplasmic dynein, it is likely that the binding interaction between dynein and liposomes is a stable one. In contrast to a previous report, microtubules increased the hydrolysis rate of all naturally occurring nucleotides tested, whereas only ATPase activity was stimulated by phospholipids. As ATP is the physiologically relevant substrate and is the only nucleotide to promote motility, the activation of only the ATPase by phospholipids may represent a means of discriminating between coupled and uncoupled nucleotide hydrolysis in vitro. PMID- 7876217 TI - A novel regulatory element of a nicotinic acetylcholine receptor gene interacts with a DNA binding activity enriched in rat brain. AB - Nicotinic acetylcholine receptors are ligand-gated ion channels that play a critical role in signal transmission in the nervous system. The genes encoding the various subunits that comprise functional acetylcholine receptors are expressed in distinct temporal and spatial patterns. Studies to understand the molecular mechanisms underlying the differential expression of the receptor subunit genes have led to the identification, in this report, of a 19-base pair cis-acting element that is required for transcriptional activation of the rat beta 4 subunit gene. Screening of computer data bases with the 19-base pair element revealed the sequence to be unique among known transcriptional regulatory elements. Loss of this element resulted in drastically reduced beta 4 promoter activity in transfected cholinergic SN17 cells. Furthermore, this element specifically interacts with nuclear proteins prepared from both SN17 cells and adult rat brain. UV cross-linking experiments indicated the presence, in SN17 nuclear extracts, of a prominent protein species (approximately 50 kDa) that interacts specifically with the 19-base pair element. These results lead us to hypothesize that interactions between the 50-kDa protein and the novel 19-base pair element are necessary for transcriptional activation of the beta 4 subunit gene. PMID- 7876218 TI - DNA structural elements required for FEN-1 binding. AB - In eukaryotic cells, a 5'-flap DNA endonuclease and a double-stranded DNA 5' exonuclease activity reside within a 42-kDa enzyme called FEN-1 (flap endonuclease-1 and 5(five)'-exonuclease). This endo/exonuclease has been shown to be highly homologous to human XP-G, Saccharomyces cerevisiae RAD2, and S. cerevisiae YKL510. Like FEN-1, these related structure-specific nucleases recognize and cleave a branched DNA structure called a DNA flap and its derivative, called a pseudo Y-structure. To dissect the important structural components of the DNA flap structure, we have developed a mobility shift assay. We find that the Fadj strand (located adjacent to the displaced flap strand) is necessary for efficient binding and cleavage of flap structures by FEN-1. When this strand is absent or when it is present, but recessed from the elbow of the flap strand, binding efficiency drops. Further investigation of the role of the Fadj strand using double flap structures reveals that the Fadj strand is necessary to provide a double-stranded template upon which FEN-1 can bind near the elbow of the flap strand. These results provide a basis for understanding how this structure-specific nuclease recognizes a variety of DNA substrates. PMID- 7876219 TI - Parameters that influence the extent of site occupancy by a candidate telomere end-binding protein. AB - The MF3 protein specifically recognizes telomeric and non-telomeric DNA probes that can form G.G base-paired structures (Gualberto, A., Patrick, R. M., and Walsh, K. (1992) Genes & Dev. 6, 815-824). Here we further characterize the nucleic acid recognition properties of MF3 and present a mathematical analysis that evaluates the potential extent of telomere site occupancy by this factor. The substitution of dI at dG positions in telomeric DNA probes revealed that a single dG at any position within the internal repeat was sufficient for high affinity binding to MF3. The RNA analogs of high affinity DNA sites were not bound specifically by MF3, but the substitution of dU for dT in a DNA probe had little or no effect on binding. These data demonstrate that ribose ring structure is a critical feature of nucleoprotein complex formation, and this ribose specificity may enable MF3 to occupy sites of unusual DNA structure while minimizing interactions with cellular RNAs. Collectively, the nucleic acid binding properties of MF3 suggest that it may occupy a significant fraction of sites at telomere ends or other G-rich regions of altered DNA structure in vivo. PMID- 7876220 TI - Arginine 132 of cellular retinoic acid-binding protein (type II) is important for binding of retinoic acid. AB - Cellular retinoic acid-binding protein type II (CRABP-II) is one of two small molecular weight, cytosolic proteins which specifically bind retinoic acid (RA). Crystallographic and site-directed mutagenesis studies of several related proteins have indicated that either one or two conserved amino acid residues, homologous to positions Arg111 and Arg132 of CRABP-II, are important for the binding of the hydrophobic ligand. In this report we have prepared site-directed mutations of these two positions of CRABP-II, Arg111 and Arg132, as well as Lys82 to determine the role of these residues in the binding of RA. Recombinant wild type and mutant CRABP-II proteins were expressed and purified, and the affinity for retinoids was determined by fluorometric titration and binding of 3H-labeled compounds. K82A displayed an identical Kd for all-trans-RA as wild type CRABP-II and the Kd for all-trans-RA of R111A was only slightly higher. On the other hand, the two Arg132 mutants, R132A and R132Q, of CRABP-II demonstrated undetectable binding of all-trans-RA. Taken together these data demonstrate that Arg132 is a critical amino acid residue for the binding of RA by CRABP-II. PMID- 7876221 TI - Amino-terminal myristoylation induces cooperative calcium binding to recoverin. AB - Recoverin, a new member of the EF-hand protein superfamily, serves as a Ca2+ sensor in vision. A myristoyl or related N-acyl group covalently attached to the amino terminus of recoverin enables it to bind to disc membranes when the Ca2+ level is elevated. Ca(2+)-bound recoverin prolongs the lifetime of photoexcited rhodopsin, most likely by blocking its phosphorylation. We report here Ca2+ binding studies of myristoylated and unmyristoylated recombinant recoverin using flow dialysis, fluorescence, and NMR spectroscopy. Unmyristoylated recoverin exhibits heterogeneous and uncooperative binding of two Ca2+ with dissociation constants of 0.11 and 6.9 microM. In contrast, two Ca2+ bind cooperatively to myristoylated recoverin with a Hill coefficient of 1.75 and an apparent dissociation constant of 17 microM. Thus, the attached myristoyl group lowers the calcium affinity of the protein and induces cooperativity in Ca2+ binding. One dimensional 1H and two-dimensional 15N-1H shift correlation NMR spectra of myristoylated recoverin measured as a function of Ca2+ concentration show that a concerted conformational change occurs when two Ca2+ are bound. The Ca2+ binding and NMR data can be fit to a concerted allosteric model in which the two Ca2+ binding sites have different affinities in both the T and R states. The T and R conformational states are defined in terms of the Ca(2+)-myristoyl switch; in the T state, the myristoyl group is sequestered inside the protein, whereas in the R state, the myristoyl group is extruded. Ca2+ binds to the R state at least 10,000 fold more tightly than to T. In this model, the dissociation constants of the two sites in the R state of the myristoylated protein are 0.11 and 6.9 microM, as in unmyristoylated recoverin. The ratio of the unliganded form of T to that of R is estimated to be 400 for myristoylated and < 0.05 for unmyristoylated recoverin. Thus, the attached myristoyl group has two related roles: it shifts the T/R ratio of the unliganded protein more than 8000-fold, and serves as a membrane anchor for the fully liganded protein. PMID- 7876222 TI - Structural analysis of human replication protein A. Mapping functional domains of the 70-kDa subunit. AB - Replication protein A (RPA) is a heterotrimeric single-stranded DNA-binding protein that is essential for DNA metabolism. Human RPA is composed of subunits of 70, 32, and 14 kDa with intrinsic DNA-binding activity localized to the 616 amino acid, 70-kDa subunit (RPA70). We have made a series of C-terminal deletions to map the functional domains of RPA70. Deletion of the C terminus resulted in polypeptides that were significantly more soluble than RPA70 but were unable to form stable complexes with the other two subunits of RPA. These data suggest that the C-terminal region of RPA70 may be important for complex formation. The DNA binding domain was localized to a region of RPA70 between residues 1 and 441. A mutant containing residues 1-441 bound oligonucleotides with an intrinsic affinity close to wild-type RPA complex. This mutant also appeared to bind with reduced cooperativity. We conclude that the C terminus of RPA70 and the 32- and 14-kDa subunits are not involved directly with interactions with DNA but may have a role in cooperativity of RPA binding. RPA70 deletion mutants were not able to support DNA replication even in the presence of a complex of the 32- and 14-kDa subunits, suggesting that the heterotrimeric complex is essential for DNA replication. The putative zinc finger in the C terminus of RPA70 is not required for single-stranded DNA-binding activity. PMID- 7876223 TI - Transcription factor GATA-1 regulates human HOXB2 gene expression in erythroid cells. AB - The human HOXB2 gene is a member of the vertebrate Hox gene family that contains genes coding for specific developmental stage DNA-binding proteins. Remarkably, within the hematopoietic compartment, genes of the HOXB complex are expressed specifically in erythromegakaryocytic cell lines and, for some of them, in hematopoietic progenitors. Here, we report the study of HOXB2 gene transcriptional regulation in hematopoietic cells, an initial step in understanding the lineage-specific expression of the whole HOXB complex in these cells. We have isolated the HOXB2 5'-flanking sequence and have characterized a promoter fragment extending 323 base pairs upstream from the transcriptional start site, which, in transfection experiments, was sufficient to direct the tissue-specific expression of HOXB2 in the erythroid cell line K562. In this fragment, we have identified a potential GATA-binding site that is essential to the promoter activity as demonstrated by point mutation experiments. Gel shift analysis revealed the formation of a specific complex in both erythroleukemic lines K562 and HEL that could be prevented by the addition of a specific antiserum raised against GATA-1 protein. These findings suggest a regulatory hierarchy in which GATA-1 is upstream of the HOXB2 gene in erythroid cells. PMID- 7876224 TI - The second kringle domain of prothrombin promotes factor Va-mediated prothrombin activation by prothrombinase. AB - The incorporation of factor Xa into the prothrombinase complex, factor Xa-factor Va-phospholipid-Ca(II), results in an approximately 10(5)-fold higher rate of substrate activation than that of the enzyme alone. To examine the role of the prothrombin kringle domains in the interaction with prothrombinase we have employed site-directed mutagenesis to produce prothrombin species that lack either the first kringle domain, PT/delta K1, or the second kringle domain, PT/delta K2. Previously, we have shown that these proteins are fully carboxylated and that they bind to phospholipid vesicles. In this investigation we demonstrate that cleavage at Arg271-Thr272 and Arg320-Ile321 peptide bonds occurs upon activation with prothrombinase to yield normal thrombin from both PT/delta K1 and PT/delta K2. In the absence of factor Va, the Km(app) for the activation of PT/delta K1, PT/delta K2, or plasma-derived prothrombin by factor Xa-phospholipid Ca(II) are equivalent. The Km(app) for the activation of PT/delta K2 by prothrombinase is approximately 4-5-fold higher than that obtained for plasma derived prothrombin or PT/delta K1. These data demonstrate that the prothrombin kringle domains do not contribute significantly to the binding affinity of the substrate-enzyme interaction. In the absence of factor Va, equivalent kcat values were obtained for all of the prothrombin species when they were activated by factor Xa-Ca(II)-phospholipid. In contrast, a 7-fold lower kcat value was obtained for the activation of PT/delta K2 by prothrombinase as compared with that obtained for plasma prothrombin or PT/delta K1. Collectively, these data suggest that determinants within the second prothrombin kringle domain interact with factor Va to elicit a significant acceleration in the catalytic rate of substrate turnover. Indeed, in contrast to plasma-derived prothrombin, no direct binding of PT/delta K2 to factor Va to form the PT/delta K2-factor Va complex could be demonstrated by 90 degrees light scattering. PMID- 7876225 TI - Type X collagen multimer assembly in vitro is prevented by a Gly618 to Val mutation in the alpha 1(X) NC1 domain resulting in Schmid metaphyseal chondrodysplasia. AB - Type X collagen is a homotrimer of alpha 1(X) chains encoded by the COL10A1 gene. It is a highly specialized extracellular matrix component, and its synthesis is restricted to hypertrophic chondrocytes in the calcifying cartilage of the growth plate and in zones of secondary ossification. Our studies on a family with Schmid metaphyseal chondrodysplasia demonstrated that the affected individuals were heterozygous for a single base substitution in the COL10A1 gene, which changed the codon GGC for glycine 618 to GTC for valine in the highly conserved region of the carboxyl-terminal NC1 domain and altered the amino acid sequence in the putative oligosaccharide attachment site. Since hypertrophic cartilage tissues or cell cultures were not available to assess the effect of the mutation, an in vitro cDNA expression system was used to study normal and mutant type X collagen biosynthesis and assembly. Full-length cDNA constructs of the normal type X collagen sequence and also cDNA containing the specific Gly to Val NC1 mutation found in the patient were produced and expressed by in vitro transcription and translation. While the control construct produced type X collagen, which formed trimeric collagen monomers and assembled into larger multimeric assemblies, the mutant collagen was unable to form these larger aggregates. These experiments demonstrated that the mutation disturbed type X collagen NC1 domain interaction and assembly, a finding consistent with the abnormal disorganized cartilage growth plate seen in the patient. These studies provide the first evidence of the effect of a type X collagen mutation on protein structure and function and directly demonstrate the critical role of interactions between NC1 domains in the formation of type X collagen multimeric structures in vitro. PMID- 7876226 TI - Modulation of the ATPase activity of the molecular chaperone DnaK by peptides and the DnaJ and GrpE heat shock proteins. AB - Previous studies have demonstrated that the Escherichia coli DnaK, DnaJ, and GrpE heat shock proteins participate in the initiation of bacteriophage lambda DNA replication by mediating the required disassembly of a preinitiation nucleoprotein structure that is formed at the phage replication origin. To gain some understanding in a simpler system of how the DnaJ and GrpE cochaperonins influence the activity of DnaK, we have examined the effect of the cochaperonins on the weak intrinsic ATPase activity of the molecular chaperone DnaK in the presence and absence of peptide effectors. We have found that random sequence peptide chains of 8 or 9 amino acid residues in length yield optimal (10-fold) activation of the DnaK ATPase, whereas peptides with 5 or fewer residues fail to stimulate the ATPase of this bacterial hsp70 homologue. Furthermore, we have discovered that those peptides that interact best with DnaK, as judged by their KA as activators of ATP hydrolysis by DnaK, also act as strong inhibitors of lambda DNA replication in vitro. The inhibitory effect of peptides on lambda DNA replication was overcome by increasing the concentration of DnaK in the replication system. Diminished inhibition was also found when the replication system was supplemented with GrpE cochaperonin, a protein known to increase the effectiveness of DnaK action in lambda DNA replication. These and other results suggest that the peptide-binding site of DnaK is required for its function in lambda DNA replication. Apparently, peptides sequester free DnaK protein and block lambda DNA replication by reducing the amount of DnaK that is free to mediate disassembly of nucleoprotein preinitiation structures. In related studies, we have found that DnaJ, like short peptides, activates the intrinsic ATPase activity of DnaK. DnaJ, however, is substantially more potent in this regard, since it activates DnaK at concentrations 1000-fold below those required for a peptide of random sequence. By itself, the GrpE cochaperonin has no effect on the peptide-independent ATPase activity of DnaK, but GrpE does vigorously stimulate the peptide-dependent ATPase of the DnaK chaperone. Under steady-state conditions, the Vmax of ATP hydrolysis by DnaK was elevated approximately 40-fold by the presence of GrpE and saturating levels of peptides. PMID- 7876227 TI - Identification of the tryptophan residue in the thiamin pyrophosphate binding site of mammalian pyruvate dehydrogenase. AB - The pyruvate dehydrogenase (E1) component of the mammalian pyruvate dehydrogenase complex catalyzes the oxidative decarboxylation of pyruvate with the formation of an acetyl residue and reducing equivalents, which are transferred sequentially to the dihydrolipoyl acetyltransferase and dihydrolipoamide dehydrogenase components. To examine the role of tryptophanyl residue(s) in the active site of E1, the enzyme was modified with the tryptophan-specific reagent N bromosuccinimide. Modification of 2 tryptophan residues/mol of bovine E1 (out of 12 in a tetramer alpha 2 beta 2) resulted in complete inactivation of the enzyme. The inactivation was prevented by preincubation with thiamin pyrophosphate (TPP), indicating that the modified tryptophan residue(s) is part of the active site of this enzyme. Fluorescence studies showed that thiamin pyrophosphate interacts with tryptophan residue(s) of E1. The magnetic circular dichroism (MCD) spectral intensity at approximately 292 nm was decreased by approximately 15% for E1 + TPP relative to the intensity for E1 alone. Because this MCD band is uniquely sensitive to and quantitative for tryptophan, the simplest interpretation is that 1 out of 6 tryptophan residues present in E1 (alpha beta dimer) interacts with TPP. The natural circular dichroism (CD) spectrum of E1 is dramatically altered upon binding TPP, with concomitant induction of optical activity at approximately 263 nm for the nonchiral TPP macrocycle. From CD studies, it is also inferred that loss of activity following N-bromosuccinimide treatment occurred without significant changes in the overall secondary structure of the protein. A single peptide was isolated by differential peptide mapping in the presence and absence of thiamin pyrophosphate following modification with N-bromosuccinimide. This peptide generated from human E1 was found to correspond to amino acid residues 116-143 in the deduced sequence of human E1 beta, suggesting that the tryptophan residue 135 in the beta subunit of human E1 functions in the active site of E1. The amino acid sequence surrounding this tryptophan residue are conserved in E1 beta from several species, suggesting that this region may constitute a structurally and/or functionally essential part of the enzyme. PMID- 7876228 TI - Cloning of an SNF2/SWI2-related protein that binds specifically to the SPH motifs of the SV40 enhancer and to the HIV-1 promoter. AB - We have isolated a human cDNA clone encoding HIP116, a protein that binds to the SPH repeats of the SV40 enhancer and to the TATA/inhibitor region of the human immunodeficiency virus (HIV)-1 promoter. The predicted HIP116 protein is related to the yeast SNF2/SWI2 transcription factor and to other members of this extended family and contains seven domains similar to those found in the vaccinia NTP1 ATPase. Interestingly, HIP116 also contains a C3HC4 zinc-binding motif (RING finger) interspersed between the ATPase motifs in an arrangement similar to that found in the yeast RAD5 and RAD16 proteins. The HIP116 amino terminus is unique among the members of this family, and houses a specific DNA-binding domain. Antiserum raised against HIP116 recognizes a 116-kDa nuclear protein in Western blots and specifically supershifts SV40 and HIV-1 protein-DNA complexes in gel shift experiments. The binding site for HIP116 on the SV40 enhancer directly overlaps the site for TEF-1, and like TEF-1, binding of HIP116 to the SV40 enhancer is destroyed by mutations that inhibit SPH enhancer activity in vivo. Purified fractions of HIP116 display strong ATPase activity that is preferentially stimulated by SPH DNA and can be inhibited specifically by antibodies to HIP116. These findings suggest that HIP116 might affect transcription, directly or indirectly, by acting as a DNA binding site-specific ATPase. PMID- 7876229 TI - An extracellular proteasome-like structure from C6 astrocytoma cells with serine collagenase IV activity and metallo-dependent activity on alpha-casein and beta insulin. AB - An extracellular proteasome-like (EP) structure has been isolated from serum-free media conditioned by C6 astrocytoma cells. EP has a native molecular mass of 1000 kDa and is composed of three subunits, two isoelectric variants at 70 kDa and one at 65 kDa. The extracellular proteasome degraded collagen IV, alpha-casein, beta insulin, and certain synthetic peptide substrates. A 68-kDa type IV collagenase, identified as the activated form of gelatinase A, was also isolated from this medium. The type IV collagenase activity of the proteasome was sensitive to serine protease inhibitors, while the 68-kDa collagenase IV represented the matrix metalloprotease gelatinase A. The general protease activity of the proteasome was sensitive to metalloprotease inhibitors. Western blot analysis indicates a sequence relationship between the 68-kDa type IV collagenase and either one or both of the 70-kDa isoelectric variants of the proteasome; however, the two enzymes appear to be distinct functionally. Comparison with known proteasomes indicates that EP represents a novel proteasome. The complexity of degradative enzymes in the extracellular microenvironment implies that complete inhibition of tumor growth requires at least a combination of serine and metalloprotease inhibitors. PMID- 7876230 TI - Zone mapping of the binding domain of the rat low affinity nerve growth factor receptor by the introduction of novel N-glycosylation sites. AB - The binding of NGF (nerve growth factor) to the rat low affinity nerve growth factor receptor (p75NGFR) has been studied by site-directed mutagenesis of the receptor. Introduction of non-native N-glycosylation sites within the binding domain indicates that the second of the characteristic cysteine-rich repeats may be particularly important to NGF binding. Two mutants of the second repeat, S42N and S66N, are glycosylated and bind NGF at a drastically reduced level, while still maintaining a conformation recognized by the monoclonal antibody against p75, MC192. Alanine substitution at these sites does not affect NGF binding. Two other mutations that result in local structural changes in the second repeat also greatly decrease binding. One of these altered residues, Ser50, appears to play an essential structural role, since it cannot be replaced by Asn, Ala, or Thr without loss of both NGF binding and MC192 recognition on a Western. Glycosylation of selected sites in the other repeats has little effect on NGF binding or antibody recognition. The introduction of non-native N-glycosylation sites may provide a generally useful scanning technique for the study of protein protein interactions. PMID- 7876231 TI - Direct observation of endocytosis of gastrin releasing peptide and its receptor. AB - Endocytosis of the gastrin releasing peptide receptor (GRP-R) may regulate cellular responses to GRP. We observed endocytosis in transfected epithelial cells by confocal microscopy using cyanine 3-GRP (cyanine 3.18-labeled gastrin releasing peptide) and GRP-R antibodies. At 4 degrees C, cy3-GRP and GRP-R were confined to the plasma membrane. After 5 min at 37 degrees C, ligand and receptor were internalized into early endosomes with fluorescein isothiocyanate transferrin. After 10 min, cy3-GRP and GRP-R were in perinuclear vesicles, and at 60 min cy3-GRP was in large, central vesicles, while GRP-R was at the cell surface. We quantified surface GRP-R using an antibody to an extracellular epitope and an 125I-labeled secondary antibody. After exposure to GRP, there was a loss and subsequent recovery of surface GRP-R. Recovery was unaffected by cycloheximide, and thus independent of new protein synthesis, but was attenuated by acidotropic agents, and therefore required endosomal acidification. Internalization of 125I-GRP, assessed using an acid wash, was maximal after 10-20 min, and was clathrin-mediated since it was inhibited by hyperosmolar sucrose and phenylarsine oxide. Thus, GRP and its receptor are rapidly internalized into early endosomes and then dissociate in an acidified compartment. GRP is probably degraded whereas the GRP-R recycles. PMID- 7876233 TI - Molecular cloning and sequencing of arylphorin-binding protein in protein granules of the Sarcophaga fat body. Implications of a post-translational processing mechanism. AB - Previously, we identified an arylphorin-binding protein of Sarcophaga peregrina (flesh fly) with a molecular mass of 120 kDa and suggested its participation in the selective uptake of arylphorin from the hemolymph into the pupal fat body at metamorphosis (Ueno, K., and Natori, S. (1984) J. Biol. Chem. 259, 12107-12111). This paper reports the isolation and sequencing of cDNA for the 120-kDa protein. This protein consists of 1146 amino acid residues. Immunoblotting and RNA blotting experiments revealed that this protein is present as two fragments of 76 kDa (695 residues) and 53 kDa (451 residues) in the larval fat body. When larvae pupate, the 120-kDa protein gene is further activated and the complete 120-kDa protein is synthesized without fragmentation. This suggests a novel mechanism for the production of the 120-kDa protein regulated by a proteinase depending upon the stage of development of Sarcophaga. All of these proteins were found to be localized in protein granules in the adipocytes. PMID- 7876232 TI - Developmental induction of Golgi structure and function in the primitive eukaryote Giardia lamblia. AB - A fundamental characteristic of eukaryotic cells is the presence of membrane bound compartments and membrane transport pathways in which the Golgi complex plays a central role in the selective processing, sorting, and secretion of proteins. The parasitic protozoan Giardia lamblia belongs to the earliest identified lineage among eukaryotes and therefore offers unique insight into the progression from primitive to more complex eukaryotic cells. Here, we report that Giardia trophozoites undergo a developmental induction of Golgi enzyme activities, which correlates with the appearance of a morphologically identifiable Golgi complex, as they differentiate to cysts. Prior to this induction, no morphologically or biochemically identifiable Golgi complex exists within nonencysting cells. Remarkably, protein secretion in both nonencysting and encysting trophozoites is inhibited by brefeldin A, and brefeldin A-sensitive membrane association of ADP-ribosylation factor and beta-COP is observed. These results suggest that the secretory machinery of Giardia resembles that of higher eukaryotes despite the absence of a Golgi complex in nonencysting trophozoites. These findings have implications both for defining the minimal machinery for protein secretion in eukaryotes and for examining the biogenesis of Golgi structure and function. PMID- 7876234 TI - Molecular cloning of a human genomic region containing the H blood group alpha(1,2)fucosyltransferase gene and two H locus-related DNA restriction fragments. Isolation of a candidate for the human Secretor blood group locus. AB - We have used the human H blood group alpha(1,2)fucosyltransferase (FUT1) cDNA to screen chromosome 19 cosmid libraries in a search for the human Secretor (Se) blood group gene (FUT2). One cosmid has been isolated that contains two distinct segments that cross-hybridize with FUT1. We have assembled a 100-kilobase (kb) cosmid contig, localized to 19q13.3, encompassing FUT1 and the two FUT1-related sequences, termed Sec1 and Sec2, for Secretor candidate 1 and 2. Sec1 and Sec2 are separated by 12 kb and are 65.5 kb and 35 kb apart, respectively, from the FUT1 gene. We used a cosmid-dependent direct cDNA selection method to clone a cDNA corresponding to a transcript that emanates from Sec2. This cDNA detects a 3.35-kb transcript in human tissues known to express the Se locus. Together with sequence and expression data reported in the accompanying article (Kelly, R. J., Rouquier, S., Giorgi, D., Lennon, G. G., and Lowe, J. B. (1995) J. Biol. Chem. 270, 4640-4649), these data demonstrate that Sec2 corresponds to the human Se blood group locus (FUT2). Our results furthermore define the physical relationship between the H and Se loci and confirm a hypothesis that these two loci represent distinct but closely linked alpha(1,2)fucosyltransferase genes. PMID- 7876236 TI - Binding of human factor VIIa to tissue factor induces cytosolic Ca2+ signals in J82 cells, transfected COS-1 cells, Madin-Darby canine kidney cells and in human endothelial cells induced to synthesize tissue factor. AB - Tissue factor (TF) is the most potent trigger of blood clotting known. It activates factor VII (FVII) thereby initiating a cascade of proteolytic reactions resulting in thrombin production. The cloning of TF revealed its structural characteristics to be those of a receptor related to the class 2 cytokine receptor superfamily, but until now no intracellular signal has been discovered related to binding of the ligand (FVIIa) to the putative receptor. We have studied possible intracellular signaling effects of the FVIIa-TF interaction by measuring cytosolic free Ca2+ in single fura-2-loaded cells and found that 200 nM FVIIa caused Ca2+ transients in about 30% of human umbilical vein endothelial cells treated with interleukin-1 beta to express TF, compared to below 5% in uninduced cells. A gradual increase of the basal Ca2+ level was also caused by binding of FVIIa. In the human bladder carcinoma cell line J82, which has a high constitutive TF activity, similar results were found. An antibody neutralizing TF activity decreased the response rate to control levels. COS-1 cells which do not make TF did not respond to FVIIa as opposed to COS-1 cells expressing TF after transfection with a human TF cDNA construct. The canine kidney cell line MDCK, a constitutive TF producer, responded especially well; up to 100% of the cells examined showed Ca2+ oscillations which were dose dependent with regard to frequency, latency, maximal amplitude, and recruitment of responding cells. The frequency was reduced by inhibition of Ca2+ influx with 100 microM LaCl3. In confluent MDCK cells the Ca2+ oscillations were synchronous, constituting the first evidence of a synchronous cytosolic Ca2+ oscillator generated by global application of agonist. Thus, TF mediates a cytosolic Ca2+ signal upon interaction with its ligand FVIIa, thereby suggesting a more complex biological role for TF. PMID- 7876235 TI - Sequence and expression of a candidate for the human Secretor blood group alpha(1,2)fucosyltransferase gene (FUT2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. AB - Synthesis of soluble A, B, H, and Lewis b blood group antigens in humans is determined by the Secretor (Se) (FUT2) blood group locus. Genetic, biochemical, and molecular analyses indicate that this locus corresponds to an alpha(1,2)fucosyltransferase gene distinct from the genetically-linked H blood group alpha(1,2)fucosyltransferase locus. The accompanying paper (Rouquier, S., Lowe, J. B., Kelly, R. J., Fertitta, A. L., Lennon, G. G., and Giorgi, D. (1995) J. Biol. Chem. 270, 4632-4639) describes the molecular cloning and mapping of two human DNA segments that are physically linked to, and cross-hybridize with, the H locus. We present here an analysis of these two new DNA segments. One of these, termed Sec1, is a pseudogene, because translational frameshifts and termination codons interrupt potential open reading frames that would otherwise share primary sequence similarity with the H alpha(1,2)fucosyltransferase. The other DNA segment, termed Sec2, predicts a 332-amino acid-long polypeptide, and a longer isoform, that share 68% sequence identity with the COOH-terminal 292 residues of the human H blood group alpha(1,2)fucosyltransferase. Sec2 encodes an alpha(1,2)fucosyltransferase with catalytic properties that mirror those ascribed to the Secretor locus-encoded alpha(1,2)fucosyltransferase. Approximately 20% of randomly-selected individuals were found to be apparently homozygous for an enzyme-inactivating nonsense allele (Trp143-->ter) at this locus, in correspondence to the frequency of the non-secretor phenotype in most human populations. Furthermore, each of six unrelated non-secretor individuals are also apparently homozygous for this null allele. These results indicate that Sec2 corresponds to the human Secretor blood group locus (FUT2) and indicate that homozygosity for a common nonsense allele is responsible for the nonsecretor phenotype in many non-secretor individuals. PMID- 7876237 TI - A constitutive effector region on the C-terminal side of switch I of the Ras protein. AB - The "switch I" region (Asp30-Asp38) of the Ras protein takes remarkably different conformations between the GDP- and GTP-bound forms and coincides with the so called "effector region." As for a region on the C-terminal side of switch I, the V45E and G48C mutants of Ras failed to promote neurite outgrowth of PC12 cells (Fujita-Yoshigaki, J., Shirouzu, M., Koide, H., Nishimura, S., and Yokoyama, S. (1991) FEBS Lett. 294, 187-190). In the present study, we performed alanine scanning mutagenesis within the region Lys42-Ile55 of Ras and found that the K42A, I46A, G48A, E49A, and L53A mutations significantly reduced the neurite inducing activity. This is an effector region by definition, but its conformation is known to be unaffected by GDP-->GTP exchange. So, this region is referred to as a "constitutive" effector (Ec) region, distinguished from switch I, a "switch" effector (Es) region. The Ec region mutants exhibiting no neurite-inducing activity were found to be correlatably unable to activate mitogen-activated protein (MAP) kinase in PC12 cells. Therefore, the Ec region is essential for the MAP kinase activation in PC12 cells, whereas mutations in this region only negligibly affect the binding of Ras to Raf-1 (Shirouzu, M., Koide, H., Fujita Yoshigaki, J., Oshio, H., Toyama, Y., Yamasaki, K., Fuhrman, S. A., Villafranca, E., Kaziro, Y., and Yokoyama, S. (1994) Oncogene 9, 2153-2157). PMID- 7876238 TI - Natriuretic peptide receptor-B (guanylyl cyclase-B) mediates C-type natriuretic peptide relaxation of precontracted rat aorta. AB - The most potent known agonist for the natriuretic peptide receptor-B (NPR B)/guanylyl cyclase-B is C-type natriuretic peptide (CNP). A homologous ligand receptor system consists of atrial natriuretic peptide (ANP) and NPR-A/guanylyl cyclase-A. A third member of this family is NPR-C, a non-guanylyl cyclase receptor. Monoclonal antibodies were raised against NPR-B by immunizing mice with a purified receptor-IgG fusion protein consisting of the extracellular domain of NPR-B and the Fc portion of human IgG-gamma 1. One monoclonal antibody, 3G12, did not recognize NPR-A or NPR-C and bound to human and rat NPR-B. CNP binding to NPR B and stimulation of cGMP synthesis were inhibited by 3G12. With cells isolated from either the media or adventitia layers of rat thoracic aorta, 3G12 did not interfere with ANP-stimulated cGMP synthesis, but it inhibited CNP-stimulated cGMP levels in cells from both layers. CNP (IC50 = 10 nM) and ANP (IC50 = 1 nM) caused relaxation of phenylephrine-contracted rat aortic rings. 3G12 caused a marked increase in the IC50 for CNP, from 10 nM to 140 nM, but failed to affect ANP-mediated relaxation. Therefore, our results for the first time demonstrate that CNP relaxes vascular smooth muscle by virtue of its binding to NPR-B. PMID- 7876239 TI - Four consecutive serines in the third intracellular loop are the sites for beta adrenergic receptor kinase-mediated phosphorylation and desensitization of the alpha 2A-adrenergic receptor. AB - During short term agonist exposure, the alpha 2A-adrenergic receptor (alpha 2AAR) undergoes rapid functional desensitization caused by phosphorylation of the receptor by the beta-adrenergic receptor kinase (beta ARK). This signal quenching is similar in nature to that found with a number of G-protein coupled receptors in which agonist-promoted desensitization is due to beta ARK phosphorylation; like these other receptors, the precise molecular determinants of the receptor required for beta ARK phosphorylation are not known. To delineate such a motif in the human alpha 2AAR (alpha 2C10), we constructed six mutated receptors consisting of deletions or substitutions of Ser-296-299 in the EESSSS sequence of the third intracellular loop of the receptor. These were expressed in Chinese hamster ovary and COS-7 cells, and agonist-promoted desensitization and receptor phosphorylation were assessed. Deletion of the EESSSS sequence and substitution of alanine for all four serines resulted in a total loss of phosphorylation and desensitization. Mutant receptors that retained two of the original serines (AASS and SSAA) underwent agonist-promoted phosphorylation of 55 +/- 7% and 57 +/- 8% of the phosphorylation found for wild type alpha 2C10. Additional substitution mutants (SSSA and SAAA) underwent 77 +/- 1% and 27 +/- 4% of wild type phosphorylation, respectively. Thus, substitution of alanine for each additional serine decreased overall phosphorylation as compared with wild type alpha 2C10 by approximately 25%, which is consistent with all 4 serines being phosphorylated. Mutated receptors that only partially phosphorylated (as compared with wild type) failed to undergo agonist-promoted desensitization. Thus, beta ARK-mediated phosphorylation of alpha 2C10 occurs at Ser-296-299 in the third intracellular loop, and this represents the critical step in rapid agonist-promoted desensitization. A number of other G-protein coupled receptors that undergo desensitization have a sequence motif similar to that which we have found for beta ARK-mediated phosphorylation of alpha 2C10, suggesting that these receptors may also be substrates for beta ARK. PMID- 7876240 TI - Human mast cell chymase and leukocyte elastase release latent transforming growth factor-beta 1 from the extracellular matrix of cultured human epithelial and endothelial cells. AB - Monolayer cultures of human epithelial and endothelial cells were used to study the association of latent transforming growth factor-beta 1 (TGF-beta 1) to extracellular matrices and its release and activation during matrix degradation. Human umbilical vein endothelial cells and embryonic lung fibroblasts produced relatively high levels of TGF-beta 1, its propeptide (beta 1-latency-associated protein), and latent TGF-beta-binding protein and incorporated latent TGF-beta 1 into their matrices as shown by immunoblotting. Amnion epithelial cells produced lower levels of these proteins. Confluent cultures of epithelial cells were exposed to matrix-degrading proteases and glycosidases. Mast cell chymase, leukocyte elastase, and plasmin efficiently released matrix-bound latent TGF-beta 1 complexes, while chondroitinase ABC and heparitinases were ineffective. The ability of the proteases to activate recombinant latent TGF-beta 1 was tested using growth inhibition assays and a novel sodium deoxycholate-polyacrylamide gel electrophoresis followed by immunoblotting. Sodium deoxycholate solubilized M(r) 25,000 TGF-beta 1 but did not dissociate high M(r) latent TGF-beta 1 complexes, allowing separation of these forms by polyacrylamide gel electrophoresis. Mast cell chymase and leukocyte elastase did not activate latent TGF-beta 1, suggesting that its release from matrix and activation are controlled by different mechanisms. The release of TGF-beta from the matrix by leukocyte and mast cell enzymes may contribute to the accumulation of connective tissue in inflammation. PMID- 7876241 TI - The molecular chaperone calnexin binds Glc1Man9GlcNAc2 oligosaccharide as an initial step in recognizing unfolded glycoproteins. AB - Calnexin is a molecular chaperone that resides in the membrane of the endoplasmic reticulum. Most proteins that calnexin binds are N-glycosylated, and treatment of cells with tunicamycin or inhibitors of initial glucose trimming steps interferes with calnexin binding. To test if calnexin is a lectin that binds early oligosaccharide processing intermediates, a recombinant soluble calnexin was created. Incubation of soluble calnexin with a mixture of Glc0-3Man9GlcNAc2 oligosaccharides resulted in specific binding of the Glc1Man9GlcNAc2 species. Furthermore, Glc1Man5-7GlcNAc2 oligosaccharides bound relatively poorly, suggesting that, in addition to a requirement for the single terminal glucose residue, at least one of the terminal mannose residues was important for binding. To assess the involvement of oligosaccharide-protein interactions in complexes of calnexin and newly synthesized glycoproteins, alpha 1-antitrypsin or the heavy chain of the class I histocompatibility molecule were purified as complexes with calnexin and digested with endoglycosidase H. All oligosaccharides on either glycoprotein were accessible to this probe and could be removed without disrupting the association with calnexin. Furthermore, the addition of 1 M alpha methyl glucoside or alpha-methyl mannoside had no effect on complex stability. These findings suggest that once complexes between calnexin and glycoproteins are formed, oligosaccharide binding does not contribute significantly to the overall interaction. However, it is likely that the binding of Glc1Man9GlcNAc2 oligosaccharides is a crucial event during the initial recognition of newly synthesized glycoproteins by calnexin. PMID- 7876242 TI - Identification of three N-terminal ends of type XVIII collagen chains and tissue specific differences in the expression of the corresponding transcripts. The longest form contains a novel motif homologous to rat and Drosophila frizzled proteins. AB - Transcripts for the alpha 1 chain of mouse type XVIII collagen were found to be heterogeneous at their 5'-ends and to encode three variant N-terminal sequences of the ensuing 1315-, 1527-, or 1774-residue collagen chains. The variant mRNAs appeared to originate from the use of two alternate promoters of the alpha 1(XVIII) chain gene, resulting in the synthesis of either short or long N terminal non-collagenous NC1 domains, the latter being further subject to modification due to alternative splicing of the transcripts. As a result, the 1527- and 1774-residue polypeptides share the same signal peptide, and the lengths of their NC1 domains are 517 or 764 amino acid residues, respectively, while the 1315-residue polypeptide has a different signal peptide and a 301 residue NC1 domain. The longest NC1 domain was strikingly characterized by a 110 residue sequence with 10 cysteines, which was found to be homologous with the previously identified frizzled proteins belonging to the family of G-protein coupled membrane receptors. Thus, it is proposed that the cysteine-rich motif, termed fz, represents a new sequence motif that can be found in otherwise unrelated proteins. Tissues containing mainly one or two NC1 domain mRNA variants or all three NC1 domains were identified, indicating that there is tissue specific utilization of two alternate promoters and alternative splicing of alpha 1(XVIII) transcripts. PMID- 7876243 TI - Copper/topa quinone-containing histamine oxidase from Arthrobacter globiformis. Molecular cloning and sequencing, overproduction of precursor enzyme, and generation of topa quinone cofactor. AB - The gene coding for histamine oxidase has been cloned and sequenced from a Coryneform bacterium Arthrobacter globiformis. The deduced amino acid sequence consists of 684 residues with a calculated molecular mass of 75,109 daltons and shows a high overall identity (58%) with that of phenethylamine oxidase derived from the same bacterial strain. Although the sequence similarities are rather low when compared with copper amine oxidases from other organisms, the consensus Asn Tyr-Asp/Glu sequence, in which the middle Tyr is the precursor to the quinone cofactor (the quinone of 2,4,5-trihydroxyphenylalanine, topa) covalently bound to this class of enzymes, is also conserved in the histamine oxidase sequence. To identify the quinone cofactor, an overexpression plasmid has been constructed for the recombinant histamine oxidase. The inactive enzyme purified from the transformed Escherichia coli cells grown in a copper-depleted medium gained maximal activity upon stoichiometric binding of cupric ions. Concomitantly with the enzyme activation by copper, a brownish pink compound was generated in the enzyme, which was identified as the quinone of topa by absorption and resonance Raman spectroscopies of the p-nitrophenylhydrazine-derivatized enzyme and found at the position corresponding to the precursor Tyr (Tyr-402). Therefore, the copper-dependent autoxidation of a specific tyrosyl residue operates on the formation of the topa quinone cofactor in this enzyme, as recently demonstrated with the precursor form of phenethylamine oxidase (Matsuzaki, R., Fukui, T., Sato, H., Ozaki, Y., and Tanizawa, K. (1994) FEBS Lett. 351, 360-364). PMID- 7876244 TI - Transport of metal-binding peptides by HMT1, a fission yeast ABC-type vacuolar membrane protein. AB - The Schizosaccharomyces pombe hmt1 gene encodes an ABC (ATP-binding cassette) type protein essential for Cd2+ tolerance. Immunoblot analysis of subcellular fractions indicates that the native HMT1 polypeptide is associated with the vacuolar membrane. Vacuolar membrane vesicles were purified from strains that hyperproduce, or are deficient in, the HMT1 protein. In vitro transport of radiolabeled substrates by these vesicles indicates that HMT1 is an ATP-dependent transporter of phytochelatins, the metal-chelating peptides involved in heavy metal tolerance of plants and certain fungi. Vacuolar vesicles containing HMT1 are capable of taking up both apo-phytochelatins and phytochelatin-Cd2+ complexes. HMT1 activity is sensitive to antibodies directed against this protein and to vanadate, but not to inhibitors affecting the vacuolar proton ATPase or ionophores that abolish the pH gradient across the vacuolar membrane. Vacuolar uptake of Cd2+ and of a glutathione conjugate were also observed, but are not attributable to HMT1. These studies highlight the importance of the yeast vacuole in detoxification of xenobiotics. PMID- 7876245 TI - The product of the Herpesvirus saimiri open reading frame 1 (tip) interacts with T cell-specific kinase p56lck in transformed cells. AB - Subgroup C strains of Herpesvirus saimiri, a leukemogenic virus of non-human primates, transform human T cells to permanent growth in culture. These cell retain their antigen specificity, and they are becoming widely used as a model for activated human T cells. Though a variety of human cell types can be infected by H. saimiri, transformation appears to be specific for CD4+ and CD8+ T cells. Our investigation of early signaling events in H. saimiri-transformed T cells revealed a novel 40-kDa phosphoprotein complexed with the T cell-specific tyrosine protein kinase p56lck. This protein, termed Tip (tyrosine kinase interacting protein), is identified as a viral protein encoded by the open reading frame 1 (ORF1). In the transformed cells Tip is expressed together with the gene product of ORF2, the viral oncoprotein StpC, which acts on epithelial cells. The H. saimiri genome has 75 ORFs, but only ORF1 and ORF2 are transcribed in transformed human cells. Tip is phosphorylated on tyrosine in cell-free systems containing Lck, indicating that the viral protein is a substrate for this T cell-specific kinase. Alteration of T cell signaling pathways by Tip may be the second event complementing the action of StpC in a new mechanism of T cell transformation. PMID- 7876246 TI - Calreticulin functions as a molecular chaperone in the biosynthesis of myeloperoxidase. AB - Myeloperoxidase (MPO), a lysosomal heme protein found exclusively in neutrophils and monocytes, is necessary for efficient oxygen-dependent microbicidal activity. Acquisition of heme by the heme-free MPO precursor apopro-MPO appears to be a prerequisite for its subsequent proteolytic processing and advancement along the biosynthetic pathway to mature MPO. We present data indicating that calreticulin (CRT), a high capacity calcium-binding protein residing in the lumen of the endoplasmic reticulum of a wide variety of cells, interacts specifically with fully glycosylated apopro-MPO. Biosynthetically radiolabeled CRT (60 kDa) and apopro-MPO (90 kDa) were coprecipitated from PLB 985 cells by monospecific antiserum against CRT when the immunoprecipitations were performed either under nondenaturing conditions or following reversible crosslinking. Nonglycosylated MPO precursors synthesized in the presence of tunicamycin did not interact with CRT. The CRT-apopro-MPO interaction was restricted to an early phase of MPO biosynthesis, and CRT did not interact with the later appearing, heme-containing species of MPO, i.e. pro-MPO or the heavy subunit of mature MPO. These data show that CRT participates in the post-translational processing of MPO, perhaps by maintaining apopro-MPO in a conformation competent to accommodate insertion of the heme group. In this general way, CRT shares certain functional properties with the structurally homologous transmembrane calcium-binding endoplasmic reticulum protein calnexin. Both interact with glycosylated biosynthetic precursors of proteins selectively expressed in specialized cells. PMID- 7876247 TI - The vitamin D receptor interacts with general transcription factor IIB. AB - The vitamin D receptor (VDR) heterodimerizes with retinoid X receptors (RXR) on many vitamin D-responsive promoter elements, suggesting that this complex is the active factor in vitamin D-mediated transcription. However, the mechanism of transcriptional regulation following VDR-RXR binding to DNA is not well characterized. Using a yeast two-hybrid protein interaction assay, we demonstrate that VDR forms specific protein: protein contacts with the basal transcription factor TFIIB. Deletion analysis indicated that the carboxyl-terminal ligand binding domain of VDR interacted with a 43-residue amino-terminal domain in TFIIB. The interaction with TFIIB showed selectivity for the ligand binding domain of VDR as similar regions of RXR alpha or of retinoic acid receptor alpha did not couple with TFIIB. Binding assays with purified proteins showed a direct interaction between VDR and TFIIB in vitro. These data suggest a mechanism for VDR-dependent transcription in which protein contacts between VDR and TFIIB may impart regulatory information to the transcription preinitiation complex. PMID- 7876248 TI - The effect of internal autocleavage on kinetic properties of the human cytomegalovirus protease catalytic domain. AB - The 28-kilodalton (kDa) catalytic domain of the human cytomegalovirus (HCMV) protease undergoes autoproteolytic cleavage at an internal site (I site), yielding amino-terminal 15-kDa (N15) and carboxyl-terminal 13-kDa (C13) fragments. I site autocleavage has been postulated to inactivate the protease and provide a mechanism for the negative regulation of enzyme activity during viral infection. We purified recombinant enzymes to demonstrate I site autocleavage in vitro and used site-directed mutagenesis of the I site to stabilize the protease. No difference in the kinetic properties of wild type and stabilized mutant proteases were observed in an in vitro peptide cleavage assay. The consequences of I site cleavage on enzyme activity were investigated two ways. First, autodigestion of the wild type enzyme converted the intact protease to N15 and C13 autocleavage products without a corresponding loss in enzyme activity. Second, genetic constructs encoding the N15 and C13 autocleavage products were generated and expressed separately in Escherichia coli, and each fragment was purified. An active enzyme was reconstituted by refolding a mixture of the purified fragments in vitro to form a noncovalent complex. The kinetic properties of this complex were very similar to the wild type and stabilized enzymes under optimal reaction conditions. We concluded from these studies that I site cleavage does not inactivate the HCMV protease, in the absence of other virally induced factors, and that limited potential exists for the regulation of catalytic activity by I site cleavage. PMID- 7876249 TI - Gel kinetic analysis of DNA polymerase fidelity in the presence of proofreading using bacteriophage T4 DNA polymerase. AB - A gel fidelity assay, previously used in the analysis of DNA polymerases having no associated 3' to 5' exonuclease activity, has been generalized for use with polymerases that contain exonucleolytic proofreading. The main purpose of this study was the development of a general analysis, using a standard Markov model, to convert experimentally observed DNA primer gel bands arising from insertion and proofreading of right and wrong deoxyribonucleotides, into nucleotide incorporation velocities and, most importantly, fidelities. The model has been applied primarily to an analysis of polymerase kinetics and fidelity in the presence of a next correct rescue dNTP, but the model can be conveniently modified to investigate other experimental designs. In the presence of rescue dNTP, direct competition occurs between excision or extension of a mismatch. At concentrations of rescue dNTP sufficient to suppress the gel band intensity at the mismatch target site, nucleotide incorporation and misincorporation rates can be obtained from the ratios of gel band intensities 3' (downstream) and 5' (upstream) to the target site, measured as a function dNTP concentration for "wrong" and "right" dNTP substrates. The polymerase misincorporation efficiency, in the presence of proofreading, is given by the ratio of wrong to right incorporation efficiencies, Vmax/Km, obtained from the gel band ratios. The bacteriophage T4 polymerase with a highly active 3'-exonuclease activity was used to illustrate the assay. Nucleotide misincorporation efficiencies measured at several template sites were dCMP.A approximately equal to 10(-6), dGMP.A approximately equal to 10(-5), dTMP.T approximately equal to 2 x 10(-4), and dAMP.A < 10(-7). Proofreading of the dGMP.A mispair was suppressed by about 3 fold in the presence of high concentrations of next correct "rescue" dNTP causing a concomitant reduction in the fidelity of dGMP.A to about 3 x 10(-5). PMID- 7876250 TI - Post-translational processing of membrane-associated neu differentiation factor proisoforms expressed in mammalian cells. AB - Expression vectors constructed from human and rat pro-neu differentiation factor (NDF) cDNAs were transfected in Chinese hamster ovary cells for expression of recombinant NDF molecules. Soluble NDF forms were released into culture medium after post-translational processing of the membrane-bound pro-NDF forms. Different human and rat NDF isoforms, after being purified from the culture medium, were subjected to structural and biochemical characterizations. The isolated human and rat NDF isoforms have been proteolytically processed at a specific site at the N terminus, which is different from that observed for the processing of rat or human NDF molecule prepared from natural origins. The processing of each recombinant NDF isoform at its C terminus was heterogeneous but consistently occurred at nearby peptide bonds. Specific N- and C-terminal processing by Chinese hamster ovary cells has resulted in the production of two types (alpha and beta) of recombinant NDFs containing 222-225 amino acid residues. Both human and rat NDF molecules are heavily glycosylated at two of the three potential Asn-linked glycosylation sites and contain O-linked sugars at 11 of the Thr/Ser sites. Glycosylation occurs at a short, Ser/Thr-rich spacer region that connects the N-terminal immunoglobulin homology unit to the epidermal growth factor domain. Cellular phosphorylation assay indicated that these secreted forms contain similar biological activity in receptor tyrosine autophosphorylation of mammary tumor cells. PMID- 7876251 TI - Studies on the structure and function of glycosylated and nonglycosylated neu differentiation factors. Similarities and differences of the alpha and beta isoforms. AB - Comparative analyses of both glycosylated and nonglycosylated neu differentiation factor (NDF) isoforms revealed significant similarities and differences of their overall structures and functions. Biophysical analyses confirmed that all NDF isoforms are monomeric, but have an extended ellipsoidal shape in solution. All full-length NDFs are similar in secondary and tertiary structures and they contain no alpha-helix but are abundant in beta-strand structures. A small NDF fragment containing only the epidermal growth factor domain is also rich in beta strand structures, but exhibits tertiary structure different from the long NDF forms. Monoclonal antibodies that selectively recognize epidermal growth factor domains of human NDF-alpha and -beta can specifically bind the respective NDF alpha and -beta isoforms independent of NDF origins. Western blot analysis and quantitative binding assays further identify that an NDF preparation produced naturally from Rat1-EJ cells contains both alpha and beta isoforms in a 3 to 2 ratio. In receptor-binding competition experiments, human and rat NDF-beta isoforms have higher affinity than NDF-alpha isoforms. NDF-beta isoforms can dramatically enhance the stimulation of DNA synthesis for transfected NIH3T3 cells that overexpress HER-3 and HER-4 receptors, while NDF-alpha isoforms can only stimulate proliferation of HER-4-transfected cells with lower activity. Taken together, NDF-alpha and -beta isoforms share similar gross protein conformations but are biologically distinct. PMID- 7876252 TI - Regulation of HIV-1 gag protein subcellular targeting by protein kinase C. AB - The human immunodeficiency virus type 1 internal structural protein precursor, p55, and its corresponding matrix proteolytic fragment, p17, are phosphorylated at Ser111 by protein kinase C. COS-7 cells transfected with plasmids encoding either the wild-type or Ser111-->Ala mutated human immunodeficiency virus type 1 gag gene matrix domain proteins were treated with phorbol 12-myristate 13-acetate (PMA), and the phosphorylation of the expressed p17 proteins was examined by radioimmunoprecipitation, SDS-polyacrylamide gel electrophoresis, and autoradiography. PMA treatment of transfected cells resulted in a 4-5-fold increase in wild-type p17 (but not mutated p17) phosphorylation; however, mutated p17 exhibited a low basal level of phosphorylation that was not affected by PMA, suggesting that additional sites were phosphorylated. PMA treatment of cells expressing wild-type p17 produced a dramatic shift in the localization of p17 from the cytosol to the membrane fraction within 8-15 min, followed by a slow quantitative dissociation of p17 back into the cytosol by 90 min. The cytosol-to membrane translocation was dependent on N-myristoylated p17 since cells expressing p17 with a Gly2-->Ala mutation did not localize to the membrane. PMA also failed to induce the translocation of fully N-myristoylated Ser111-->Ala p17, suggesting that p17 phosphorylation at Ser111 was responsible for membrane association. This conclusion was confirmed by the finding of phosphorylated wild type p17 in the membrane fraction only after PMA treatment. These results suggest that a "myristoyl-protein switch" regulates the reversible membrane targeting of p17 by protein kinase C-mediated phosphorylation. This signal may provide a mechanism for the cellular regulation of virus development through modulation of gag protein-related developmental steps such as capsid targeting, assembly, encapsidation, budding, and maturation. PMID- 7876253 TI - Intracellular folding of tissue-type plasminogen activator. Effects of disulfide bond formation on N-linked glycosylation and secretion. AB - The addition of N-linked core oligosaccharides to membrane and secretory glycoproteins occurs co-translationally at asparagine residues in the tripeptide sequon Asn-Xaa-Ser/Thr soon after translocation of the nascent polypeptide into the lumen of the endoplasmic reticulum. However, the presence of the sequon does not automatically ensure core glycosylation, as many proteins contain sequons that remain either unglycosylated or glycosylated to a variable extent. To investigate whether intracellular protein folding can influence sequon utilization, we have expressed tissue-type plasminogen activator (t-PA) in cell culture in the presence of mild concentrations of the reducing agent dithiothreitol to prevent co-translational disulfide bond formation in the endoplasmic reticulum. We show that conditions that prevent disulfide bond formation lead to complete glycosylation of a sequon that otherwise undergoes variable glycosylation in untreated cells. This demonstrated that folding and disulfide bond formation of t-PA determines its extent of core N-linked glycosylation. When dithiothreitol was removed from the cells, the reduced and overglycosylated t-PA formed disulfide bonds, folded, and was secreted. We also show t-PA present within cells is more susceptible to reduction with low concentrations of dithiothreitol than secreted t-PA. PMID- 7876254 TI - Characterization of Rad, a new member of Ras/GTPase superfamily, and its regulation by a unique GTPase-activating protein (GAP)-like activity. AB - We have recently identified a new member of the Ras/GTPase superfamily termed Rad which has unique sequence features and is overexpressed in the skeletal muscle of humans with type II diabetes (Reynet, C., and Kahn, C. R. (1993) Science, 262, 1441-1444). When expressed in bacteria as a glutathione S-transferase fusion protein, Rad bound [alpha-32P]GTP quickly and saturably. Binding was specific for guanine nucleotides and displayed unique magnesium dependence such that both GTP and GDP binding were optimal at relatively high Mg2+ concentrations (1-10 mM). Rad had low intrinsic GTPase activity which was greatly enhanced by a GTPase activating protein (GAP) activity present in various tissues and cell lines. Several known GAPs had no stimulatory effect toward Rad. Conversion of Ser to Asn at position 66 in Rad (equivalent to position 12 in Ras) resulted in a total loss of GTP binding. Mutation of Pro61 (equivalent to Gly12 in Ras) or Gln109 (equivalent to Gln61 in Ras) had no effect on Rad GTPase activity, whereas creation of a double mutation at these positions resulted in exceptionally high intrinsic GTPase activity. In vitro, Rad was phosphorylated by the catalytic subunit of cAMP-dependent protein kinase (PK). Phosphopeptide mapping indicated two PKA phosphorylation sites near the COOH terminus. Rad also co-precipitated a serine/threonine kinase activity from extracts of various tissues and cell lines which catalyzed phosphorylation on Rad but was not inhibited by PKA inhibitor. Thus, Rad is a GTP-binding protein and a GTPase which has some structure/function similarities to Ras, but displays unique features. Rad may also be phosphorylated on serine/threonine residues by PKA and other kinases, as well as regulated by its own GAP which is present in many tissues and cell types. PMID- 7876255 TI - Novel proteins of the phosphotransferase system encoded within the rpoN operon of Escherichia coli. Enzyme IIANtr affects growth on organic nitrogen and the conditional lethality of an erats mutant. AB - Two rpoN-linked delta Tn10-kan insertions suppress the conditionally lethal erats allele. One truncates rpoN while the second disrupts another gene (ptsN) in the rpoN operon and does not affect classical nitrogen regulation. Neither alter expression of era indicating that suppression is post-translational. Plasmid clones of ptsN prevent suppression by either disruption mutation indicating that this gene is important for lethality caused by erats. rpoN and six neighboring genes were sequenced and compared with sequences in the database. Two of these genes encode proteins homologous to Enzyme IIAFru and HPr of the phosphoenolpyruvate:sugar phosphotransferase system. We designate these proteins IIANtr (ptsN) and NPr (npr). Purified IIANtr and NPr exchange phosphate appropriately with Enzyme I, HPr, and Enzyme IIA proteins of the phosphoenolpyruvate: sugar phosphotransferase system. Several sugars and tricarboxylic acid cycle intermediates inhibited growth of the ptsN disruption mutant on medium containing an amino acid or nucleoside base as a combined source of nitrogen, carbon, and energy. This growth inhibition was relieved by supplying the ptsN gene or ammonium salts but was not aleviated by altering levels of exogenously supplied cAMP. These results support our previous proposal of a novel mechanism linking carbon and nitrogen assimilation and relates IIANtr to the unknown process regulated by the essential GTPase Era. PMID- 7876256 TI - Gq pathway desensitizes chemotactic receptor-induced calcium signaling via inositol trisphosphate receptor down-regulation. AB - Desensitization of a chemotactic receptor is an adaptive process that terminates inflammation. Although homologous desensitization can be well explained by the action of specific receptor kinases, the mechanisms of heterologous desensitization remain elusive. As an approach to evaluate the roles of Gq pathway in desensitization of calcium signaling, we expressed a constitutively active Gq alpha mutant (Gq alpha Q-L) together with platelet-activating factor (PAF) receptor in Xenopus laevis oocytes. Gq alpha Q-L expression completely attenuated the calcium-sensitive chloride current and the 45Ca release elicited by PAF. The Gq-mediated desensitization could not be ascribed to G protein/receptor uncoupling via receptor phosphorylation, because (i) PAF-induced inositol 1,4,5-trisphosphate (IP3) synthesis was only partially suppressed and (ii) a mutated PAF receptor devoid of all Ser and Thr in the third cytoplasmic loop and in the C-terminal tail was also completely desensitized by Gq alpha Q-L. In Gq alpha Q-L expressing oocytes, microinjection of IP3 failed to elicit the calcium response, and the IP3 receptor, detected by a specific antibody, disappeared. Thus, the Gq-mediated desensitization can be most likely explained by IP3 receptor down-regulation. These novel mechanisms may explain in part heterologous desensitization in chemotactic factor-stimulated inflammatory cells. PMID- 7876257 TI - The Schizosaccharomyces pombe homologue of the chaperone calnexin is essential for viability. AB - We have cloned a Schizosaccharomyces pombe gene, here designated cnx1, encoding the homologue of the endoplasmic reticulum molecular chaperone calnexin. Disruption of the cnx1 gene was lethal, demonstrating that it has an essential cellular function. Transcription of cnx1 mRNA is initiated at multiple sites, and it can be induced by various stress treatments that lead to the accumulation of unfolded and/or misfolded proteins in the endoplasmic reticulum. The encoded Cnx1p protein more closely resembles its plant and animal calnexin homologues than that of Saccharomyces cerevisiae. Cnx1p is acidic and migrates aberrantly on SDS-polyacrylamide gel electrophoresis, similar to its mammalian counterparts. Cnx1p contains the hallmark KPEDWD motifs that are found in all members of the calnexin/calreticulin family of proteins. Using an in vitro translation processing system, we have shown that Cnx1p has the characteristic type I topology of calnexin proteins. Unlike its higher eukaryotic homologues, Cnx1p has a site for N-glycosylation that was modified in an in vitro translation processing assay. PMID- 7876258 TI - Dephosphorylation of Alzheimer paired helical filaments by protein phosphatase-2A and -2B. AB - Microtubule-associated protein tau is abnormally hyperphosphorylated in the brain of patients with Alzheimer disease and in this form is the major protein subunit of the paired helical filaments (PHF), the most prominent lesion of the disease. In this study the dephosphorylation of sparingly soluble PHF, PHF II-tau by brain protein phosphatase (PP)-2A1 and PP-2B, and the resulting biochemical, biological, and structural alterations were investigated. Both of the phosphatases dephosphorylated PHF II-tau at the sites of Ser-199/Ser-202 and partially dephosphorylated it at Ser-396/Ser-404; in addition, PHF II-tau was dephosphorylated at Ser-46 by PP-2A1 and Ser-235 by PP-2B. The relative electrophoretic mobility of PHF II-tau increased after dephosphorylation by either enzyme. Divalent cations, manganese, and magnesium increased the activities of PP-2A1 and PP-2B toward PHF II-tau. Dephosphorylation both by PP-2B and PP-2A1 decreased the resistance of PHF II-tau to proteolysis by the brain calcium-activated neutral proteases (CANP). The ability of PHF II-tau to promote the in vitro microtubule assembly was restored after dephosphorylation by PP-2A1 and PP-2B. Microtubules assembled by the dephosphorylated PHF II-tau were structurally identical to those assembled by bovine tau used as a control. The dephosphorylation both by PP-2A1 and PP-2B caused dissociation of the tangles and the PHF; some of the PHF dissociated into straight protofilaments/subfilaments. Approximately 25% of the total tau was released from PHF on dephosphorylation by PP-2A1. These observations demonstrate that PHF II-tau is accessible to dephosphorylation by PP-2A1 and PP-2B, and dephosphorylation makes PHF dissociate, accessible to proteolysis by CANP, and biologically active in promoting the assembly of tubulin into microtubules. PMID- 7876259 TI - Recombinant human insulin receptor substrate-1 protein. Tyrosine phosphorylation and in vitro binding of insulin receptor kinase. AB - Insulin receptor substrate-1 (IRS-1) is a major endogenous substrate of the insulin receptor. To study the interaction of the insulin receptor with IRS-1 in vitro, we expressed in Escherichia coli the amino acids 516-777 of human IRS-1 (hIRS-p30) covering five potential tyrosine phosphorylation sites within YXXM motifs. Kinetic data for tyrosine phosphorylation of hIRS-p30 by partially purified insulin receptor and insulin-like growth factor I receptor and by baculovirus-expressed insulin receptor kinase domain were determined. Native insulin receptor demonstrated the highest affinity to hIRS-p30 (Km = 6.8 +/- 0.6 microM), followed by the insulin-like growth factor I receptor (Km = 9.9 +/- 1.0 microM). We used the soluble recombinant insulin receptor kinase domain, which phosphorylated hIRS-p30 with high affinity (Km = 11.9 +/- 0.8 microM), and affinity columns prepared by coupling hIRS-p30 to NHS-activated Sepharose for binding assays. The insulin receptor kinase domain phosphorylated the hIRS-p30 on the column, was bound by the immobilized hIRS-p30, and was eluted with high salt buffer. Autophosphorylated and EDTA-inactivated insulin receptor kinase domain was bound only by immobilized hIRS-p30 protein that has been prephosphorylated. Our results indicate that the recombinant hIRS-p30 protein is a high affinity substrate for insulin receptor and insulin-like growth factor I receptor in vitro. Moreover, we show that only tyrosine-phosphorylated hIRS-p30 is able to bind to the insulin receptor. PMID- 7876260 TI - Heterogeneous nuclear ribonucleoprotein K is a DNA-binding transactivator. AB - We have previously reported that heterogeneous nuclear ribonucleoprotein K (hnRNP K) binds to the pyrimidine-rich strand of the CT element found in the human c-myc gene and activates CT reporter-driven gene expression in vivo. We now characterize the DNA and protein requirements for the interaction of hnRNP K with the CT element. First, hnRNP K is shown to preferentially bind single-stranded DNA over RNA or native double-stranded DNA. Using specific oligoribonucleotide or deoxyribonucleotide probes with specific or nonspecific RNA or DNA competitors, electrophoretic mobility shift assay revealed hnRNP K to be a DNA-binding protein. Specific binding was not simply a reflection of binding to pyrimidine rich sequences as the number and arrangement of individual CT elements governed interactions with hnRNP K; at least two CT repeats separated by at least three nucleotides are required for binding, indicating the existence of particular stereochemical constraints regulating CT-hnRNP K complex formation. Deletion analysis showed that hnRNP K possesses several nonoverlapping, DNA binding domains, each capable of specific binding with the CT element and preferring DNA over RNA. Each sequence recognition domain is composed of at least one K homology motif, while a larger portion of hnRNP K may be required for stable RNA binding. Additional experiments indicate that the N-terminal 35 residues of hnRNP K are necessary for transactivating the CT element. These results indicate that hnRNP K is a DNA-binding protein and transcriptional activator. PMID- 7876261 TI - Structure and function of transcription-repair coupling factor. I. Structural domains and binding properties. AB - The 130-kDa mfd gene product is required for coupling transcription to repair in Escherichia coli. Mfd displaces E. coli RNA polymerase (Pol) stalled at a lesion, binds to the damage recognition protein UvrA, and increases the template strand repair rate during transcription. Here, the interactions of Mfd (transcription repair coupling factor, TRCF) with DNA, RNA Pol, and UvrA were investigated. TRCF bound nonspecifically to double stranded DNA; binding to DNA produced alternating DNase I-protected and -hypersensitive regions, suggesting possible wrapping of the DNA around the enzyme. Weaker binding to single stranded DNA and no binding to single stranded RNA were observed. DNA binding required ATP, and hydrolysis of ATP promoted dissociation. Removal of a stalled RNA Pol also requires ATP hydrolysis. Apparently, TRCF recognizes a stalled elongation complex by directly interacting with RNA Pol, since binding to a synthetic transcription bubble was no stronger than binding to double stranded DNA, and binding to free RNA Pol holoenzyme and to initiation and elongation complexes in the absence of adenosine 5'-O-(thiotriphosphate) were observed. Structure-function analysis showed that residues 379-571 are involved in binding to a stalled RNAP. The helicase motifs region, residues 571-931, binds to ATP and duplex polynucleotide (DNA:DNA or DNA:RNA). Dissociation of the ternary complex upon hydrolysis of ATP also requires the carboxyl terminus of TRCF. Finally, residues 1-378 bind to UvrA and deliver the damage recognition component of the excision nuclease to the lesion. PMID- 7876262 TI - Structure and function of transcription-repair coupling factor. II. Catalytic properties. AB - The transcription repair coupling factor (TRCF) of Escherichia coli has the so called helicase motifs, is a DNA-, RNA Pol-, and UvrA-binding protein, and is required for the coupling of repair to transcription. We investigated the potential helicase, transcription termination, and transcription-repair coupling activities of TRCF on various substrates. We found that TRCF does not have a helicase activity on any of the substrates tested. However, the TRCF releases both RNA Pol and the truncated transcript from a transcriptional road block caused by a lesion, a "missing base," or a DNA-bound protein. It does not have any effect on rho-dependent or rho-independent transcriptional termination. However, some premature terminations were induced by TRCF at other sites. The coupling of transcription to repair occurs with supercoiled and relaxed circular DNA and with linear DNA. However, the coupling with linear DNA is strongly affected by the length of the DNA and does not occur with fragments in which the lesion is closer than 90 nucleotides to the 5' terminus of the template strand. Under transcription conditions the repair of lesions in the promoter region and up to the eleventh transcribed base is inhibited even in the presence of TRCF. Stimulation of repair in the transcribed strand starts at lesions at +15 nucleotides. Stimulation of repair occurs via facilitating the delivery of the A2B1 complex to the lesion site by the TCRF and can be inhibited by excess UvrA which binds to the TRCF off DNA. In vitro, strand-specific repair is not dependent on the MutL and MutS proteins which have recently been implicated in preferential repair in vivo. PMID- 7876263 TI - The general transcription-repair factor TFIIH is recruited to the excision repair complex by the XPA protein independent of the TFIIE transcription factor. AB - Recent studies have revealed that the general transcription factor TFIIH is also a general excision repair factor which, along with several other proteins, is required for transcription-independent excision reaction. As a general transcription factor, TFIIH is recruited to RNA polymerase II-promoter complex by another general transcription factor called TFIIE. We were interested in knowing whether TFIIE is also involved in recruiting TFIIH to the excision repair complex. We found that cell-free extract depleted of TFIIE carried out excision repair at a normal rate, leading us to conclude that TFIIE is not involved in recruiting TFIIH to the damage site and has no role in general excision repair. In contrast, the human damage recognition protein XPA specifically binds to TFIIH and apparently recruits it to the damage site. The carboxyl-terminal half of XPA is responsible for specific interaction with TFIIH. The C261S/C264S mutant of XPA bound the ERCC1-XPF complex normally, but failed to bind TFIIH and failed to complement an XP-A mutant cell-free extract indicating that the XPA-TFIIH interaction is essential to effecting the excision reaction. Interestingly, XPA also binds to the p34 subunit of TFIIE specifically and in competition with the p56 subunit of TFIIE. This latter interaction has no apparent role in general excision repair but may be relevant in the transcription-coupled repair reaction. PMID- 7876264 TI - Immediate interaction between the nascent subunits and two conserved amino acids Trp34 and Thr206 are needed for the catalytic activity of aspartylglucosaminidase. AB - Aspartylglucosaminidase (AGA, EC 3.5.1.26) is a dimeric lysosomal hydrolase involved in the degradation of glycoproteins. The synthesized precursor polypeptide of AGA is rapidly activated in the endoplasmic reticulum by proteolysis into two subunits. Expression of the alpha- and beta-subunits of AGA in separate cDNA constructs showed that independently folded subunits totally lack enzyme activity, and even when co-expressed in vitro they fail to produce an active heterodimer of the enzyme. Both of the subunits are required for the enzyme activity, and the immediate interaction of the subunits in the endoplasmic reticulum is necessary for the correct folding of the dimeric enzyme molecule. The specific amino acid residues essential for the active site of the AGA enzyme were further analyzed by site-directed mutagenesis and in vitro expression of mutagenized constructs. Replacement of Thr206, the most amino-terminal residue of the beta-subunit, with Ser resulted in a complete loss of enzyme activity without influencing intracellular processing or transport of the mutant polypeptide to the lysosomes. Analogously, replacement of the most amino-terminal tryptophan, Trp34 with Phe or Ser in the alpha-subunit, resulted in a totally inactive enzyme without influencing the intracellular processing or stability of the polypeptide. These results suggest that the catalytic center of this amidase is formed by the interaction of the amino-terminal parts of two subunits and requires both Trp34 in the alpha-subunit and Thr206 in the beta-subunit. PMID- 7876265 TI - Overexpression and characterization of the human peroxisomal acyl-CoA oxidase in insect cells. AB - Human liver peroxisomes contain two acyl-CoA oxidases, namely, palmitoyl-CoA oxidase and a branched chain acyl-CoA oxidase. The palmitoyl-CoA oxidase (ACOX) oxidizes the CoA esters of straight chain fatty acids and prostaglandins and donates electrons directly to molecular oxygen, thereby producing H2O2. The inducibility of this H2O2-generating ACOX in rat and mouse liver by peroxisome proliferators and the postulated role of the resulting oxidative stress in hepatocarcinogenesis generated interest in characterizing the structure and function of human ACOX. We have constructed a full-length cDNA encoding a 660 amino acid residue human ACOX and produced a catalytically active human ACOX protein at high levels in Spodoptera frugiperda (Sf9) insect cells using the baculovirus vector. Immunoblot analysis demonstrated that the full-length 72-kDa polypeptide (component A) was partially processed into its constituent 51-kDa (component B) and 21-kDa (component C) products, respectively. Recombinant protein (approximately 20 mg/l x 10(9) cells) was purified to homogeneity by a single-step procedure on a nickel-nitrilo-triacetic acid affinity column. Using the purified enzyme, Km and Vmax values for palmitoyl-CoA were found to be 10 microM and 1.4 units/mg of protein, respectively. The maximal activities for saturated fatty acids were observed with C12-18 substrates. The overexpressed human ACOX protein was identified in the cytoplasm of the insect cells by immunocytochemical staining. Individual expression of either the truncated ACOX 51-kDa (component B) or the 21-kDa (component C) revealed lack of enzyme activity, but co-infection of the insect cells with recombinant viruses expressing components B and C resulted in the formation of an enzymatically active heterodimeric B+C complex which could subsequently be inactivated by dissociating with detergent. PMID- 7876266 TI - Muscarinic regulation of Alzheimer's disease amyloid precursor protein secretion and amyloid beta-protein production in human neuronal NT2N cells. AB - The Alzheimer amyloid precursor protein (APP) undergoes complex processing resulting in the production of a 4-kDa amyloid peptide (A beta) which has been implicated in the pathogenesis of Alzheimer's disease. Recent studies have shown that cells can secrete carboxyl terminus truncated APP derivatives (APP-S) in response to physiological stimulus. We have used human central nervous system neurons (NT2N) derived from a teratocarcinoma cell line (NT2) to study the signal transduction pathways involved in APP-S secretion and A beta production. Muscarinic receptors (m2 and m3) as well as the heterotrimeric GTP-binding protein Gq and the beta 1 isoform of phospholipase C were present in NT2N neurons. Stimulation of the muscarinic receptor with carbachol resulted in phospholipase C activation as shown by a transient increase in the second messengers 1,2-diacyl-sn-glycerol and inositol 1,4,5-trisphosphate. Carbachol also caused an increase in intracellular Ca2+ levels measured in single NT2N neurons. Under these conditions, carbachol caused a time-dependent 2-fold increase in APP-S secretion into the medium. In contrast, prolonged treatment with carbachol caused a decrease in A beta production into the medium. These results suggest that APP-S secretion and A beta production in NT2N neurons are regulated by the muscarinic/phospholipase C signal transduction pathway. Furthermore, activation of this pathway results in dissociation of APP-S secretion and A beta production. PMID- 7876267 TI - The peptide mastoparan is a potent facilitator of the mitochondrial permeability transition. AB - Mastoparan facilitates opening of the mitochondrial permeability transition pore through an apparent bimodal mechanism of action. In the submicromolar concentration range, the action of mastoparan is dependent upon the medium Ca2+ and phosphate concentration and is subject to inhibition by cyclosporin A. At concentrations above 1 microM, pore induction by mastoparan occurs without an apparent Ca2+ requirement and in a cyclosporin A insensitive manner. Studies utilizing phospholipid vesicles show that mastoparan perturbs bilayer membranes across both concentration ranges, through a mechanism which is strongly dependent upon transmembrane potential. However, solute size exclusion studies suggest that the pores formed in mitochondria in response to both low and high concentrations of mastoparan are the permeability transition pore. It is proposed that low concentrations of mastoparan influence the pore per se, with higher concentrations having the additional effect of depolarizing the mitochondrial inner membrane through an action exerted upon the lipid phase. It may be the combination of these effects which allow pore opening in the absence of Ca2+ and in the presence of cyclosporin A, although other interpretations remain viable. A comparison of the activities of mastoparan and its analog, MP14, on mitochondria and phospholipid vesicles provides an initial indication that a G-protein may participate in regulation of the permeability transition pore. These studies draw attention to peptides, in a broad sense, as potential pore regulators in cells, under both physiological and pathological conditions. PMID- 7876268 TI - Different domains of the AP-1 adaptor complex are required for Golgi membrane binding and clathrin recruitment. AB - The assembly of clathrin-coated buds on the Golgi requires the recruitment of the heterotetrameric AP-1 adaptor complex, which is dependent on both guanine nucleotides and the small GTP-binding protein ADP-ribosylation factor (ARF). Here, we have investigated the structural domains of the AP-1 complex necessary for ARF-mediated translocation of the adaptor complex onto Golgi membranes and the subsequent recruitment of clathrin onto the membrane. Controlled proteolysis of purified AP-1, derived from bovine adrenal coated vesicles, was used to generate AP-1 core fragments composed of the amino-terminal trunk regions of the beta 1 and gamma subunits and associated mu 1 and sigma 1 subunits, and lacking either the beta 1 subunit carboxyl-terminal appendage or both beta 1 and gamma subunit appendages. On addition of these truncated fragments to AP-1-depleted adrenal cytosol, both types of core fragments were efficiently recruited onto Golgi membranes in the presence of GTP gamma S. Recruitment of both core fragments was inhibited by the fungal metabolite brefeldin A, indicative of an ARF-dependent process. Limited tryptic digestion of recruited, intact cytosolic AP-1 resulted in the quantitative release of the globular carboxyl-terminal appendage domains of the beta 1 and gamma subunits. The adaptor core complex remained associated with the Golgi membranes. Recruitment of cytosolic clathrin onto the Golgi membranes was strictly dependent on the presence of intact AP-1. Tryptic removal of the beta 1 subunit appendage prevented subsequent clathrin recruitment. We conclude that the structural determinants required for the ARF mediated binding of cytosolic AP-1 onto Golgi membranes are contained within the adaptor core, and that the carboxyl-terminal appendage domains of the beta 1 and gamma subunits do not play any role in this process. Subsequent recruitment of cytosolic clathrin, however, requires an intact beta 1 subunit. PMID- 7876269 TI - Occurrence of three-stranded DNA within a RecA protein filament. AB - A RecA protein-generated triple-stranded DNA species can be observed by electron microscopy, within narrowly defined conditions. Three-stranded DNA is detected only when initiation of normal DNA strand exchange is precluded by heterologous sequences within the duplex DNA substrate, when ATP is hydrolyzed, and when the DNA is cross-linked with a psoralen derivative prior to removal of RecA filaments. When adenosine 5'-O-(thiotriphosphate) is used, only the product hybrid duplex DNA can be cross-linked within the RecA filament. The third strand is either displaced or interwound in a conformation that does not permit cross linking. When ATP is hydrolyzed by RecA, all three strands are cross-linked within the filament in a complex pattern that suggests a dynamic structure. This structure is altered when RecA protein is removed before cross-linking. Hsieh et al. (1990) and Rao et al. (1991, 1993) have proposed, on the basis of nuclease protection and chemical modification studies, that a stable triple-stranded DNA species can persist after removal of RecA protein. We have been unable to visualize these triple-stranded structures by the methods used in the present investigation. When RecA removal was followed immediately by interstrand cross linking, only the two strands of the hybrid duplex DNA were cross-linked. PMID- 7876270 TI - Phosphorylation of a Fes-related protein in response to granulocyte-macrophage colony stimulating factor. AB - Previous work has suggested that a 97-kDa protein (p97) is involved in the signal transduction pathway of granulocyte-macrophage colony stimulating factor (GM-CSF) as well as interleukin 3, erythropoietin, and interleukin 2. We have examined the relationship of p97 to the protein tyrosine kinase Fes in the GM-CSF signal transduction pathway in erythroid and myeloid cell lines. GM-CSF stimulation of three different cell lines induced tyrosine phosphorylation of p97 as well as a number of other phosphotyrosylproteins. Although each cell line expressed the proto-oncogene product Fes, antisera specific for Fes did not recognize p97 in immunoblotting experiments. Furthermore, immunodepletion of Fes did not reduce the amount of p97 in GM-CSF-treated cells. Two-dimensional gel electrophoresis demonstrated that p97 and Fes have similar charge to mass ratios, and limited proteolytic mapping of p97 and Fes suggested that these proteins may be related but are not identical. Our studies demonstrate that p97 is not Fes but is probably a Fes-related protein. PMID- 7876271 TI - Alpha 1A-adrenoceptor subtype mediates contraction of the rat urethra. AB - 1. The alpha 1-adrenoceptor-mediated responses of the rat urethra to phenylephrine have been examined in vitro. Phenylephrine caused concentration dependent contractions of the isolated urethra which were antagonized by WB4101 (3-30 nM) and prazosin (10-100 nM) but not idazoxan (1.5 microM). Schild plot analysis of the antagonism by prazosin and WB4101 yielded straight lines with slopes not significantly different from unity. The pA2 value of 9.0 for WB4101 was significantly greater than the value previously obtained at the alpha 1B adrenoceptor of the rat spleen. 2. 5-Methylurapidil (30 nM) and abanoquil (1 nM) caused dextral shifts of concentration-response curves yielding pKB values of 8.3 and 9.4 respectively. Maximal responses to phenylephrine were also reduced by this concentration of abanoquil. 3. Preincubation with chloroethylclonidine (25 microM for 40 min) failed to alter responses, but removing extracellular calcium or the presence of nifedipine (1 microM) almost abolished contractions to phenylephrine. 4. These results indicate that the responses of the rat urethra to phenylephrine are mediated via the alpha 1A-adrenoceptor subtype and are dependent on the influx of extracellular calcium. PMID- 7876272 TI - Pharmacological characterization of the inhibitory effect of (R)-alpha methylhistamine on sympathetic cardiopressor responses in the pithed guinea-pig. AB - 1. The effect of (R)-alpha-methylhistamine (R-alpha-mHA), a selective histamine H3-receptor agonist, on increases in blood pressure and heart rate mediated by activation of the sympathetic nervous system induced by electrical stimulation of the spinal cord, was characterized in the vagotomized, pithed guinea-pig. 2. The frequency-dependent nature of (R)-alpha-mHA's effect on sympathetic cardiopressor responses was studied at frequencies between 1 and 20 Hz. (R)-alpha-mHA (10-100 micrograms kg-1, i.v.) produced a dose-dependent inhibition of the stimulated increase in both blood pressure (BP) and heart rate (HR). The inhibition was inversely related to frequency and maximum inhibition (BP, 61% at 1 Hz; HR, 50% at 1 Hz) was seen with 100 micrograms kg-1 of (R)-alpha-mHA. Treatment with the H3 receptor inactive stereoisomer, (S)-alpha-methylhistamine (300 micrograms kg 1, i.v.) did not inhibit the neurogenic sympathetic cardiopressor responses. 3. Pretreatment with thioperamide (1 mg kg-1, i.v.), a histamine H3 receptor antagonist, blocked (R)-alpha-mHA's inhibitory effect on stimulation-induced sympathetic cardiopressor responses. 4. Combined pretreatment with the H2 receptor antagonist cimetidine (3 mg kg-1, i.v.) and the H1-receptor antagonist chlorpheniramine (0.3 mg kg-1, i.v.) did not attenuate (R)-alpha-mHA's inhibitory effects. 5. (R)-alpha-mHA (100 micrograms kg-1) had no effect on the hypertensive or tachycardia effects induced by adrenaline (1 and 3 micrograms kg-1, i.v.). 6. Treatment with a combination of prazosin (1 mg kg-1, i.v.) and yohimbine (1.5 mg kg-1, i.v.) to block alpha 1- and alpha 2-adrenoceptors, abolished the sympathetic hypertension without affecting the inhibition of sympathetic tachycardia induced by (R)-alpha-mHA. Conversely, pretreatment with the beta adrenoceptor antagonist propranolol (1 mg kg-1, i.v.), which blocked the sympathetic tachycardia, did not block (R)-alpha-mHA's inhibition of sympathetic hypertensive responses. 7. In adrenalectomized guinea-pigs, (R)-alpha-mHA (100 micrograms kg-1, i.v.) also produced a frequency-dependent inhibition of sympathetic hypertensive cardiopressor responses that was not significantly different from intact animals. 8. These results demonstrate that (R)-alpha-mHA produces a frequency-dependent inhibition of the cardiopressor responses due to activation of the sympathetic innervation to the resistance vessels and the heart.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7876273 TI - Influence of the baroreceptor reflex on the modulation of noradrenaline overflow through prejunctional receptors in the portal vein of freely moving rats. AB - 1. The effects of alterations in mean arterial blood pressure (MAP), as induced by vasoactive drugs, on heart rate (HR), basal noradrenaline concentration and electrically evoked noradrenaline overflow and on blood flow in the portal vein of freely moving rats, were investigated. 2. By infusion of sodium nitroprusside or phenylephrine (0.5, 1.0 and 2.5 micrograms kg-1 min-1), MAP was altered over a range of 50 to 150 mmHg. The resulting changes in HR showed a sigmoidal relationship with MAP. Noradrenaline overflow increased linearly when MAP was decreased; when MAP was increased, however, noradrenaline levels only decreased to 70% and reached a plateau from 125 mmHg onwards. 3. Nitroprusside (2.5 micrograms kg-1 min-1) and fenoterol (0.25 mg kg-1) decreased MAP to the same extent (-46 mmHg). HR and basal noradrenaline concentration, however, were increased to a higher extent by fenoterol (+192 beats min-1; +373 pg ml-1, respectively) than by nitroprusside (+78 beats min-1; +206 pg ml-1, respectively). Electrically evoked overflow was not changed at all after nitroprusside, whereas fenoterol induced an increase to 206% of control. 4. Phenylephrine (2.5 micrograms kg-1 min-1) and angiotensin II (1 microgram kg-1 min-1) increased MAP to the same extent (to 155 and 161 mmHg, respectively). Basal noradrenaline concentration decreased by 30% after phenylephrine, whereas angiotensin II increased noradrenaline levels to 226% of control. Evoked noradrenaline overflow was not changed after phenylephrine but was increased to 204% of control after angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876274 TI - Effect of chemical sympathectomy on (-)-isoprenaline-induced changes in cardiac beta-adrenoceptor subtypes in the guinea-pig and rat. AB - 1. Quantitative autoradiography was used to determine beta-adrenoceptor densities in cardiac regions of guinea-pigs and rats after chemical sympathectomy with 6 hydroxydopamine, and to examine how chemical sympathectomy affected beta adrenoceptor changes following infusion of (-)-isoprenaline (400 micrograms kg-1 hr-1, 7 days). 2. Seven days after 6-hydroxydopamine (100 mg kg-1, i.v.), cardiac tissue levels of noradrenaline were reduced by 94.0 +/- 3.5% (guinea-pig) and 86.0 +/- 7.0% (rat). The blood pressure increase in rats to tyramine (0.5 mg, i.v.) was reduced from 118 mmHg in controls to 4.4 mmHg in 6-hydroxydopamine treated animals. 3. There were no changes 7 and 14 days after 6-hydroxydopamine treatment in total, beta 1-and beta 2-adrenoceptor density in the atrioventricular conducting system and atrial and ventricular myocardium in both species. 4. In control animals, (-)-isoprenaline infusion produced selective reductions in beta 2-adrenoceptor density, whilst beta 1-adrenoceptor density remained unchanged. 5. In 6-hydroxydopamine treated guinea-pigs or rats, (-) isoprenaline infusion caused no change in beta 1-adrenoceptors except in the right bundle branch whilst beta 2-adrenoceptors were reduced in the atrioventricular conducting system (atrioventricular node, bundle of His, right and left bundle branches) and myocardium (interventricular septum and atria). 6. The differential effect of (-)-isoprenaline on beta 1- and beta 2-adrenoceptors is not therefore due to the occupation of beta 1-adrenoceptors by noradrenaline or to prior down-regulation of beta 1-adrenoceptors by noradrenaline, since it persists after depletion of noradrenaline. PMID- 7876275 TI - Functional beta-adrenoceptors in the left atrium of normotensive and hypertensive rats. AB - 1. The aim of the study was to characterize the functional beta 1-and beta 2 adrenoceptors of the rat left atrium and to investigate how these functional beta adrenoceptor responses were altered in hypertension. The contractile responses of the left atrium from Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats to isoprenaline, T-0509 and procaterol were characterized. Subsequently, the effects of selective beta 1-(bisoprolol) and beta 2 (ICI 118,551)-adrenoceptor antagonists were investigated on these responses. 2. The maximal combined contractile responses of the rat left atrium to cardiac stimulation and CaCl2, isoprenaline, T-0509 or procaterol were not altered by hypertension. 3. The sensitivities to CaCl2 (pD2 on WKY left atrium = 2.99), isoprenaline (8.82) and T 0509 (8.84) were not altered by hypertension. There was an increase in sensitivity to procaterol from a pD2 value of 7.21 to 7.61 in the left atrium of the SH rat. 4. The basal tension induced by cardiac stimulation alone was inhibited by bisoprolol at > or = 10(-8) M and by ICI 118,551 at > or = 10(-7) M and this inhibitory effect is probably due to membrane stabilizing activity. 5. The pKB values for bisoprolol against isoprenaline, T-0509 and procaterol on the WKY were 8.43, 8.68 and 8.18, respectively, and were not different from SH rat left atrium. 6. The pKB value for ICI 118,551 against isoprenaline was increased from 7.06 on the WKY to 7.44 on the SH rat left atrium. The pKB values for ICI 118,551 against T-0509 and procaterol on the WKY were 7.18 and 8.14, respectively and were not significantly different from the SH rat left atrium values. 7. These results suggest that: (a) procaterol stimulates the beta 1-, in addition to, the beta 2-adrenoceptors of the rat left atrium; (b) functional beta 1-adrenoceptors are not altered in hypertension, and (c) there is probably an increase in the affinity of procaterol and isoprenaline for the beta 2-adrenoceptors which underlies the small increase in the functional beta 2-adrenoceptor response in hypertension. PMID- 7876276 TI - Endothelial injury during extracorporeal circulation: neutrophil-endothelium interaction induced by complement activation. AB - This study was designed to understand the physiologic intravascular and intradevice events at the cellular level following complement system activation during extracorporeal circulation. The addition of anaphylatoxin C5a or complement-activated serum into neutrophil- or endothelial cell-suspensions resulted in a dose-dependent transmembrane stimulation that was assessed by an intracellular free calcium ion mobilization technique using a calcium-sensitive photoprotein, aequorin. The adhesion and ruffle formation of neutrophils on endothelial cell monolayers were markedly enhanced when both cell types were treated with C5a or activated serum. The significance of complement activation on intravascular events during extracorporeal circulation is emphasized and discussed from the viewpoint of surface-expressed adhesion molecules. PMID- 7876277 TI - In vitro flexural fatigue limits of dental composites. AB - The flexural fatigue test equipment developed was used to study the fatigue behavior of dental restorative composites, using a "staircase" approach. Three commercial composites were tested after dry and wet storage conditions. The findings indicate that the method is accurate and reliable, and that changes due to water sorption are clearly reflected: The flexural fatigue limit decreases after water sorption. From the present results it seems that under environmentally controlled conditions, the fatigue behavior is characterized by a well-defined fatigue stress level above which the composites tested fail rapidly, and below which they survive. PMID- 7876278 TI - Studies on calcium phosphate precipitation: effects of metal ions used in dental materials. AB - The effects of 26 metal ions, of which 23 are used in dental materials, on the conversion of amorphous calcium phosphate (ACP) to hydroxyapatite (HAP) in vitro were studied. From the effects on both the rate of HAP transformation and induction time, effects of metal ions were classified into three types; inhibitory (in the order: nickel, tin, cobalt, manganese, copper, zinc, gallium, thallium, molybdenum, cadmium, antimony, magnesium, and mercury); ineffective (cesium, titanium, chromium, iron [ferrous], iridium, palladium, platinum, silver, gold, aluminum, and lead); and stimulatory (iron [ferric] and indium). These results suggest that metal ions used in dental materials may modify the precipitation of oral calcium phosphate. PMID- 7876279 TI - Dual constant composition kinetics characterization of apatitic surfaces. AB - The use of calcium phosphate phases as implant materials in forms such as ceramic hydroxyapatite (CHAP) and hydroxyapatite plasma-coated implants (HPCTI) as well as the synthetic phases is now quite well established. Although conventional physical chemical characterization methods such as X-ray diffraction may indicate the exclusive presence of hydroxyapatite (HAP), there is little doubt that other calcium-containing surface impurities play important roles in the initial reactions that take place when such materials are brought into contact with aqueous phases. These surface impurities usually dissolve rapidly with the release of excess calcium and hydroxide ions. Based on the constant composition (CC) method, the dual constant composition (DCC) approach has been developed for investigating the dissolution kinetics behavior of these apatitic materials in an attempt to characterize and modify the surfaces, and possibly to predict their behavior when placed in vivo. The results of this study confirm the presence of highly reactive heterogeneous calcium-containing phases on the surface of materials such as CHAP and HPCTI, as evidenced by the release of appreciable amounts of calcium and hydroxyl ions upon introduction of these surfaces in saline solutions. Furthermore, these calcium phosphate phases exhibited a unique dissolution behavior when compared with synthetically prepared phases such as HAP and beta-tricalcium phosphate (beta-TCP), as suggested by the observation that they dissolve in solutions supersaturated with respect to HAP. PMID- 7876280 TI - Surface energy characterization of unalloyed titanium implants. AB - Osteointegration is dependent on a variety of biomechanical and biochemical factors. One factor is the wettability of an implant surface that is directly influenced by its surface energy. This investigation used the Zisman plot to determine critical surface tension as one representative measurement of surface energy. The effects of surface treatment, bulk grain size, and surface roughness on the critical surface tension of unalloyed titanium (Ti) were examined. Radio frequency glow discharge-treated Ti had the highest critical surface tension, followed by the passivated and heat-sterilized conditions. Titanium with no surface treatment had the lowest critical surface tension. The surface energy of Ti with an average grain size of 23 microns was not significantly different from that with a grain size of 70 microns. Surface roughness was shown to cause significant difference in measurements and definitely should be considered in studies of this kind. PMID- 7876281 TI - Atomic force microscopy studies of the interaction of a dentin adhesive with tooth hard tissue. AB - The usefulness of atomic force microscopy (AFM) in the study of dental biomaterials was investigated. Two basic points were addressed: the first is the use of an atomic force microscope for the imaging of tooth hard tissue; the second is a study by AFM of the interaction of a liquid adhesive (Gluma) with dentin. Results show that dental tissues are readily imaged by AFM and that high resolution images of the dentin ultrastructure can be obtained. As to the dentin adhesive, it was possible to elucidate the mechanism of action of Gluma. In particular, polymerization of the hydroxyethylmethacrylate present in the Gluma mixture was observed to occur in < 30 seconds. PMID- 7876282 TI - Splenic response to silicon drain material following intraperitoneal implantation. AB - To study the splenic response to intraperitoneal biomaterials, 100% silicon rubber drain fragments were intraperitoneally implanted in the rat. Four days after implantation, specimens of the spleen and implanted rubber fragment were retrieved and subjected to scanning electron microscopy (SEM) and energy dispersive X-ray microanalysis (EDX). In SEM, macrophages with membrane fusion and cytoplasmic spreading were noted on the surfaces of implanted rubber fragments. Specimens of the spleen from animals with implants showed light 3-10 microns structures that were not observed in those without implants. EDX revealed the presence of silicon both in the rubber fragment and in the spleen of the implanted animals. Both light microscopy and transmission electron microscopy showed a large number of particles inside giant cells of the spleen. The present study demonstrated an active transport of rubber fragments containing silicon from the peritoneal cavity to the spleen by adherent macrophages, reflecting a splenic response to intraperitoneal implantation of biomaterials. The modes of silicon rubber degradation and transportation remain to be elucidated. PMID- 7876283 TI - Mineralization and pH relationships in healing skeletal defects grafted with demineralized bone matrix. AB - Early studies had indicated that tissue repair is initially associated with a lower than normal serum pH that later becomes more alkaline. To determine how tissue pH may affect skeletal healing and mineralization, we used a rat skeletal repair model consisting of a long bone segmental defect grafted with acid demineralized bone matrix (DBM), a biomaterial possessing both osteoinductive and osteoconductive repair properties. In this study, femoral and tibial diaphyses from young adult Sprague Dawley rats were cut into cylinders approximately 0.5 cm in length, demineralized in acid, perforated to accommodate a needle-type combination pH microelectrode, and grafted around a 0.3-cm-long diaphyseal fibula defect. The pH of repair tissues was recorded at various time intervals up to 28 days postgrafting. Healing and mineralization were monitored histologically and by the ash and calcium content of repair tissues. During the early healing phase, tissue pH was lower than normal serum pH, presumably because of an accumulation of acidic metabolites in tissue fluids. Subsequent pH increases to more alkaline values were accompanied by a rapid mineral deposition phase and a later phase characterized by a slow, gradual increase in tissue calcium content. The results of this study support previous observations suggesting that the pH of repair tissue fluids may play a regulatory role in the healing and mineralization of bone. PMID- 7876284 TI - Osteoblast function on synthetic biodegradable polymers. AB - Rat osteoblasts were cultured on films of biodegradable poly(L-lactic acid) (PLLA), 75:25 poly(DL-lactic-co-glycolic acid) (PLGA), 50:50 PLGA, and poly(glycolic acid) (PGA) for up to 14 days. Osteoblasts attached equally well to all the polymer substrates after 8 h in culture. By day 4 in culture, osteoblasts had exceeded confluency numbers, and their proliferation leveled off by day 7. An increase in alkaline phosphatase (ALP) activity from 1.92 (+/- 0.47) x 10(-7) for day 7 to 5.75 (+/- 0.12) x 10(-7) mumol/cell per min for day 14 was reported for osteoblasts cultured on 75:25 PLGA, which was comparable to that observed for tissue culture polystyrene (TCPS) controls. The ALP activities expressed by osteoblasts cultured on PLLA, 50:50 PLGA, and PGA films did not significantly increase over time. Collagen synthesis for osteoblasts cultured on all polymer substrates was similar to that of TCPS and did not vary with time. The morphology of cultured osteoblasts was not affected by the continuous degradation of the polymer substrates. These results demonstrate that poly(alpha-hydroxy esters) can provide a suitable substrate for osteoblast culture and hold promise in bone regeneration by osteoblast transplantation. PMID- 7876285 TI - Inflammatory response and degradation of three types of calcium phosphate ceramic in a non-osseous environment. AB - The cellular response and inflammatory reaction to three types of calcium phosphate ceramic spheres, namely fluorapatite (FA), hydroxyapatite (HA), and beta-tricalcium phosphate (TCP), were investigated. The degradation at ultrastructural level of these ceramics was also studied. The mouse peritoneal cavity was used as a model compartment for this study. To minimize the influence of a wound reaction, the spheres were implanted by injection. Intraperitoneal injection of latex beads of 6.4 and 25.7 microns showed that an inflammatory reaction is influenced by the size of injected particles; therefore, ceramic spheres with the same average diameter (11.3 microns) were used. After 2 and 4 days and 1, 2, 4, 8, 12, and 24 weeks, the spheres were harvested. All materials gave rise to a short, mild inflammatory reaction. The ceramic spheres aggregated rapidly, and foreign body granulomas were formed within 2 weeks. Degradation of all materials was observed in this study, and degradation products were frequently seen both intracellularly and extracellularly. After 2 weeks TCP and HA showed the formation of crystals at their surface and between individual grains of the spheres. This was most prominently seen with TCP. At 4 weeks, HA and TCP granulomas showed the formation of extracellular, globular deposits between macrophages or multinucleated giant cells and fragments of the ceramic. They consisted of an organic matrix containing apatite-like crystals and iron, and had an average diameter of 10 microns. The number of deposits was the highest for TCP. For FA, calcium phosphate precipitation and the formation of deposits was not observed before the 8-week interval and remained at a low level. PMID- 7876286 TI - Erosion of a new family of biodegradable polyanhydrides. AB - Studies investigating the erosion mechanism of the newly developed poly (fatty acid dimer: sebacic acid) polyanhydride (p:[FAD:SA]) are described. The overall erosion of different monomer compositions of p(FAD:SA) copolymers was examined to determine whether and to what extent copolymer properties affected polymer erosion. Increasing the hydrophobic monomer (FAD) content up to 50 wt% in the copolymer resulted in longer erosion, whereas further increases up to 70 wt% decreased the erosion period. Polymer crystallinity depended on copolymer FAD content. Copolymer degradation was studied by examining anhydride bond hydrolysis using infrared spectroscopy. Much faster hydrolysis was found in p(FAD:SA) 70:30 compared with more crystalline copolymers of higher SA content. Light microscopy indicates the presence of an erosion zone, a distinct area where mass loss occurs. This erosion zone moves from the outside toward the interior of the polymer matrix. It plays an important role in erosion because any water or monomer must diffuse through this eroded layer. PMID- 7876287 TI - Study of the surface characteristics of magnetron-sputter calcium phosphate coatings. AB - Plasma-sprayed hydroxylapatite coatings on metals such as titanium have been investigated for many years and have shown a good biocompatibility when implanted in bony tissues. Radiofrequency magnetron sputtering was used as an alternative method to deposit thin films of hydroxylapatite on titanium substrates. X-ray diffraction demonstrated that the sputtered layer was crystalline with a preferred (001) crystallographic orientation with the C-axis perpendicular to the substrate surface. Scanning electron microscopy showed that the deposited films had a uniform and dense structure. The calcium phosphate ratio varied between 1.5 and 2.0, as determined by energy-dispersive X-ray analysis. The in vitro dissolution appeared to be determined by the degree of the coating's crystallinity. PMID- 7876288 TI - Effect of 2-amino oleic acid exposure conditions on the inhibition of calcification of glutaraldehyde cross-linked porcine aortic valves. AB - Postimplant calcific degeneration is a frequent cause of clinical failures of glutaraldehyde cross-linked porcine bioprosthetic heart valves (BPHV). It was demonstrated previously that 2-amino oleic acid (AOA) used as a bioprosthesis treatment was highly effective in mitigating aortic valve cusp but not aortic wall calcification. Our main objective was to study the efficacy of various AOA exposure conditions for inhibiting calcification of both cusps and aortic wall tissues using rat subdermal implants. BPHV tissues were treated with a saturated AOA solution for different time intervals before experimental. Aortic wall AOA levels were consistently lower than that of the cusps after the same exposure times. The diffusion of calcium ion across both cusp and aortic wall tissues was evaluated, and the results demonstrated that there was an AOA exposure time dependent retardation of calcium ion penetration for cusp but not aortic wall. An 8-month extraction study was performed to determine the stability of AOA binding. When Tween 80 was used as an extraction medium, cusp and aortic wall retained 12.9 and 48.7%, respectively, of their initial AOA levels. AOA inhibition of calcification in rat subdermal implants (60 days) was found to be exposure time dependent with maximum treatment time (120 h), resulting in the lowest calcium levels (20.1 +/- 10.3 and 71.4 +/- 5.4 micrograms/mg of cusp and aortic wall, respectively) as compared with controls (219.1 +/- 6.8 and 104.9 +/- 8.5 micrograms/mg of cusp and aortic wall, respectively). The significance of AOA binding on BPHV tissue was determined by either blocking or reducing BPHV's (cusp and aortic wall) free aldehyde residues with lysine or NaBH4, respectively, before AOA treatment. For aortic cusps, the AOA contents after 72 h were 98.3 +/- 2.7, 34.2 +/- 3.6, and 54.1 +/- 3.0 nM/mg of tissue for AOA (control), lysine pretreated (plus AOA) and NaBH4-pretreated (plus AOA) tissues, respectively. However, their calcium levels after 60 days of rat subdermal implant were all comparable (i.e., 48.1 +/- 6.2, 38.2 +/- 9.1, and 47.0 +/- 15.0 micrograms calcium per mg of tissue). Similar results were observed on BPHV aortic wall. It can thus be concluded that AOA inhibition of BPHV calcification is exposure time dependent, but the efficacy of AOA for aortic wall is less than that noted for aortic cusps, perhaps because of lower AOA binding and differences in calcium diffusion kinetics. PMID- 7876289 TI - Pre-marital fertility in Liberia. AB - This analysis of the 1986 Liberia Demographic and Health Survey data finds remarkably high fertility levels among women who have never married or lived with a man, reflecting widespread pre-marital sex and a lack of use of contraception. It is found that single Liberian women are more likely to foster out children than married Liberian women of the same age. PMID- 7876291 TI - A survey of Papua New Guinean parturients at the Port Moresby General Hospital: family planning. AB - A survey of 673 consecutive Papua New Guinean parturients at the Port Moresby General Hospital, in May and June 1990, showed that 28% had ever used a family planning (FP) method, chiefly a hormonal method (93% of ever-users). Only seventeen of 239 (7.1%) nulliparae had ever used an FP method, compared with 170 of 434 (39.2%) parous subjects. Education of mother and of husband were independently and significantly associated with FP ever-use. Seventeen (4.9%) of 347 women who had a surviving child, had not breast-fed the child. The interval between the birth of the surviving child and the start of the index pregnancy was significantly associated with the duration of breast-feeding; the longer the duration of breast-feeding, the longer the inter birth interval. PMID- 7876290 TI - Patterns of cortisol and adrenaline variation in Australian aboriginal communities of the Kimberley region. AB - Urinary cortisol and adrenaline excretion rates were measured in three Australian Aboriginal communities in the Kimberley region in the north-west of the country. The three communities, Derby, Kalumburu and Kupungarri, differ in size and remoteness and some lifestyle parameters. Cortisol excretion rate is associated with age and urine flow rate, but there is no association with smoking or the consumption of alcohol. All three communities show very high cortisol excretion rates compared to a sample of UK (Oxford) residents and there are also differences between the three communities. Adrenaline excretion rate also shows associations with age and urine flow rate, but not with smoking. Aboriginal people in the Kimberley region excrete adrenaline at a slightly higher rate than that found in Oxford, which itself is high by world standards. There are no marked differences between communities in their adrenaline excretion rates. Alcohol drinkers in Derby, where alcohol is freely available, have higher adrenaline output than non-drinkers. PMID- 7876292 TI - A triplet maternity in a reduced population with excessive twinning. AB - In 1991 a triplet maternity of same-sex (FFF) occurred in a depopulated community of Argyll, Scotland, with a history of excessive, same-sex twinning. Due to a stillbirth and its confidentiality, the maternity was recorded as a twin birth. Using public registers may result in underestimation of rates for higher multiple conceptions and births in local districts. PMID- 7876293 TI - Age variations in the proximate determinants of child mortality in south-west Nigeria. AB - Age variations in the influences of three sets of proximate factors on child survival in Ondo State, Nigeria, during 1981-86 are described. Biodemographic factors covary very strongly with mortality risks during the first month of life, weakly during months 1-11, and imperceptibly beyond infancy. Microenvironmental factors progressively strongly covary with mortality after the neonatal period, while health services accessibility and care factors broadly covary strongly with mortality throughout early childhood. Patterns in the size of the hypothetical population-level impacts of these factors suggest that promoting assisted use of toilet facilities within households by under-5s and wider provision of dispensaries and hospitals would yield cost-effective and notable reductions in overall childhood mortality levels in the study setting. PMID- 7876294 TI - Sterilisation as a method of contraception: recent trends in Great Britain and their implications. AB - Data on patterns and trends in sterilisation in Britain among women, men and couples are presented using life table approaches with data from a national survey, the General Household Survey. Among couples under age 50, sterilisation is the main method of contraception used, with slightly more women than men being sterilised, although this is reversed if only contraceptive sterilisation is considered. Trends in contraception have remained relatively constant in recent decades. Patterns of sterilisation differ following births of different orders. For example, the resort to sterilisation is much quicker after a third birth than after a second. The proportions of men and women who have been sterilised and then formed a subsequent partnership are very small, so the effect of sterilisation in preventing births in such unions is negligible. PMID- 7876295 TI - Demographic and sociocultural factors influencing contraceptive use in Uganda. AB - Bivariate and multivariate analyses of the influence of demographic and sociocultural factors on contraceptive knowledge, attitudes and practice among currently married respondents in Uganda show that: (1) contraceptive knowledge is widespread, even among women with no education; (ii) the majority of the respondents have favourable attitudes towards contraceptive use; (iii) the level of contraceptive use is low in comparison with knowledge and attitudes. Post primary education, ethnicity, residence, the presence of the spouse in the household and discussion of family planning with spouse were strong predictors of knowledge and favourable attitudes towards contraception. Secondary or higher education, discussion of family planning with spouse and urban residence strongly influenced contraceptive use, but child mortality did not. The use of condoms as a behavioural change to avoid contracting HIV/AIDS was low. The results suggest that, particularly in rural areas, family planning services are not meeting the needs of potential clients. PMID- 7876296 TI - Biodemographic alterations derived from reservoir building in a rural settlement in Spain. AB - The building of dams to collect water for hydroelectricity and irrigation brings about environmental alterations and hence the appearance of a new ecosystem. These changes affect the human environment and result in demographic, social and economic alterations of the original settlements. In the mountainous regions of Palencia in the north of Spain, three dams have been built this century. This paper analyses the biodemographic modifications in the settlement directly affected by the construction of these dams, and compares it with nearby control settlements with similar demographic and social structure, in order to establish the effects of the flooding of extensive areas. PMID- 7876297 TI - Old age security and inheritance in Nepal: motives versus means. AB - This paper documents expectations of old age support in rural Nepal. Current living arrangements of the elderly have been analysed with a focus on the ownership of land holdings. It is argued that the intergenerational transfer of property through inheritance from the older to the younger generation, especially among sons, together with the Nepali normative prescription that sons care for their aged parents, provides a mechanism for old age support. However, land is becoming a scarce resource, cultural traditions are breaking down through modernisation and the living conditions of the elderly are likely to deteriorate as this process continues. PMID- 7876298 TI - Religion and fertility in the Outer Hebrides. AB - Estimates of fertility in Protestant Barra and Catholic Harris, islands in the Outer Hebrides, over the period 1856-1985, show that in both islands fertility declined, although marital fertility was generally greater than in Scotland as a whole, and illegitimate fertility was less. However, in Barra during 1966-75 there were pronounced rises in all the indices; illegitimate fertility showed the smallest rise. The publication of the papal encyclical Humanae Vitae may have played a part in this change in fertility, although other, probably local, factors must have been acting, as the first rise in numbers of births occurred before the publication of the encyclical. Other than this transient rise, the religious difference between Harris and Barra had little effect on changes in fertility over the whole period. Indices of proportions married showed declines until after World War 2, followed by steep increases. The marked decline in fertility in both islands may be due in part to this low nuptiality. In addition, a trend of occupation away from traditional crofting and fishing towards more skilled mercantile and professional employment may have played a role. PMID- 7876299 TI - Determinants of infant mortality in Malawi: an analysis to control for death clustering within families. AB - The 1988 Malawi Traditional and Modern Methods of Child Spacing Survey data are used to identify determinants of infant mortality in Malawi. The logistic binomial analysis shows that socioeconomic factors are significant even during the neonatal period while the length of the preceding birth interval is significant in the post-neonatal period only. There is a strong familial correlation of mortality risks during both the neonatal and post-neonatal periods but the effect of geographical area of residence is stronger in the post-neonatal period. PMID- 7876300 TI - Reconstituted nuclei depleted of a vertebrate GLFG nuclear pore protein, p97, import but are defective in nuclear growth and replication. AB - Xenopus egg extracts provide a powerful system for in vitro reconstitution of nuclei and analysis of nuclear transport. Such cell-free extracts contain three major N-acetylglucosaminylated proteins: p200, p97, and p60. Both p200 and p60 have been found to be components of the nuclear pore. Here, the role of p97 has been investigated. Xenopus p97 was isolated and antisera were raised and affinity purified. Immunolocalization experiments indicate that p97 is present in a punctate pattern on the nuclear envelope and also in the nuclear interior. Peptide sequence analysis reveals that p97 contains a GLFG motif which defines a family of yeast nuclear pore proteins, as well as a peptide that is identical at 11/15 amino acids to a specific member of the GLFG family, NUP116. An additional peptide is highly homologous to a second sequence found in NUP116 and other members of the yeast GLFG family. A monoclonal antibody to the GLFG domain cross reacts with a major Xenopus protein of 97 kD and polyclonal antiserum to p97 recognizes the yeast GLFG nucleoporin family. The p97 antiserum was used to immunodeplete Xenopus egg cytosol and p97-deficient nuclei were reconstituted. The p97-depleted nuclei remained largely competent for nuclear protein import. However, in contrast to control nuclei, nuclei deficient in p97 fail to grow in size over time and do not replicate their chromosomal DNA. ssDNA replication in such extracts remains unaffected. Addition of the N-acetylglucosaminylated nuclear proteins of Xenopus or rat reverses these replication and growth defects. The possible role(s) of p97 in these nuclear functions is discussed. PMID- 7876301 TI - Nuclear localization of the testis determining gene product SRY. AB - We have studied the expression of the human SRY protein (termed p27SRY) in two different cell lines by using specific antibodies. Confocal microscopy enabled us to localize p27SRY precisely in the nucleus in a discrete punctuate pattern. Furthermore, through microinjection experiments, we have demonstrated that the localization of the p27SRY protein into the nucleus was an event involving the NH2-terminal part of the high mobility group (HMG) domain. With the help of several synthetic peptides and various p27SRY mutants, we have characterized a bipartite basic motif in this part of the protein corresponding to a nuclear localization signal. This nuclear localization signal appears to be highly conserved in SRY box- and HMB box-containing proteins, suggesting common properties of nuclear targeting within the HMG box protein family. PMID- 7876302 TI - CEP3 encodes a centromere protein of Saccharomyces cerevisiae. AB - We have designed a screen to identify mutants specifically affecting kinetochore function in the yeast Saccharomyces cerevisiae. The selection procedure was based on the generation of "synthetic acentric" minichromosomes. "Synthetic acentric" minichromosomes contain a centromere locus, but lack centromere activity due to combination of mutations in centromere DNA and in a chromosomal gene (CEP) encoding a putative centromere protein. Ten conditional lethal cep mutants were isolated, seven were found to be alleles of NDC10 (CEP2) encoding the 110-kD protein of yeast kinetochore. Three mutants defined a novel essential gene CEP3. The CEP3 product (Cep3p) is a 71-kD protein with a potential DNA-binding domain (binuclear Zn-cluster). At nonpermissive temperature the cep3 cells arrest with an undivided nucleus and a short mitotic spindle. At permissive temperature the cep3 cells are unable to support segregation of minichromosomes with mutations in the central part of element III of yeast centromere DNA. These minichromosomes, when isolated from cep3 cultures, fail to bind bovine microtubules in vitro. The sum of genetic, cytological and biochemical data lead us to suggest that the Cep3 protein is a DNA-binding component of yeast centromere. Molecular mass and sequence comparison confirm that Cep3p is the p64 component of centromere DNA binding complex Cbf3 (Lechner, 1994). PMID- 7876304 TI - Human SEC13Rp functions in yeast and is located on transport vesicles budding from the endoplasmic reticulum. AB - In the yeast Saccharomyces cerevisiae, Sec13p is required for intracellular protein transport from the ER to the Golgi apparatus, and has also been identified as a component of the COPII vesicle coat structure. Recently, a human cDNA encoding a protein 53% identical to yeast Sec13p has been isolated. In this report, we apply the genetic assays of complementation and synthetic lethality to demonstrate the conservation of function between this human protein, designated SEC13Rp, and yeast Sec13p. We show that two reciprocal human/yeast fusion constructs, encoding the NH2-terminal half of one protein and the COOH-terminal half of the other, can each complement the secretion defect of a sec13-1 mutant at 36 degrees C. The chimera encoding the NH2-terminal half of the yeast protein and the COOH-terminal half of the human protein is also able to complement a SEC13 deletion. Overexpression of either the entire human SEC13Rp protein or the chimera encoding the NH2-terminal half of the human protein and the COOH-terminal half of the yeast protein inhibits the growth of a sec13-1 mutant at 24 degrees C; this growth inhibition is not seen in a wild-type strain nor in other sec mutants, suggesting that the NH2-terminal half of SEC13Rp may compete with Sec13 1p for a common target. We show by immunoelectronmicroscopy of mammalian cells that SEC13Rp (like the putative mammalian homologues of the COPII subunits Sar1p and Sec23p) resides in the region of the transitional ER. We also show that the distribution of SEC13Rp is not affected by brefeldin A treatment. This report presents the first demonstration of a putative mammalian COPII component functioning in yeast, and highlights a potentially useful approach for the study of conserved mammalian proteins in a genetically tractable system. PMID- 7876303 TI - Chromokinesin: a DNA-binding, kinesin-like nuclear protein. AB - Microtubule-associated mechanoenzymes have been proposed to play a fundamental role in chromosome movement. We have cloned and characterized the cDNA for a novel protein, named Chromokinesin, that fulfills several of the criteria expected of a mitotic motor. Chromokinesin contains both a kinesin motor-like domain and an unusual basic-leucine zipper DNA-binding domain. Its mRNA is readily detectable in proliferating cells, but not in postmitotic cells. Immunocytochemical analysis with antibodies directed against the nonconserved COOH-terminal region of Chromokinesin indicates that the protein is localized in the nucleus, and primarily associated with chromosome arms in mitotic cells. These data suggest that Chromokinesin is likely to function as a microtubule based mitotic motor with DNA as its cargo. PMID- 7876305 TI - A Chinese hamster ovary cell mutant defective in the non-endocytic uptake of fluorescent analogs of phosphatidylserine: isolation using a cytosol acidification protocol. AB - Transmembrane movement of phosphatidylserine (PS) and various PS analogs at the plasma membrane is thought to occur by an ATP-dependent, protein-mediated process. To isolate mutant CHO cells defective in this activity, we first obtained conditions which inhibited the endocytic, but not the non-endocytic pathway of lipid internalization since PS may enter cells by a combination of these two pathways. We found that acidic treatment of cells, which blocks clathrin-dependent endocytosis, enhanced the energy-dependent uptake of 1 palmitoyl-2-(6-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]caproyl -sn- glycero-3 phosphoserine (C6-NBD-PS) in CHO cells from donor vesicles (liposomes) by about twofold. Control experiments demonstrated that the enhanced uptake of C6-NBD-PS at acidic pH was not due to: (a) an increase in the capacity of the plasma membrane to incorporate C6-NBD-PS from the donor vesicles; (b) a decrease in the rate of loss of C6-NBD-PS from the cells; or (c) fusion or engulfment of the donor vesicles. When cytosolic acidification (to pH 6.3) was imposed without acidification of the extracellular medium, C6-NBD-PS uptake by intact cells was increased by about 50% compared to control values determined in the absence of acidification. These results suggested that a protein and energy dependent system(s) for transbilayer movement of the fluorescent PS was stimulated by cytosolic acidification. A screening method for mutant cells defective in the non endocytic uptake of fluorescent PS analogs with replica cell colonies at acidic pH was then devised. After selection of mutagenized CHO-K1 cells by in situ screening, we obtained a mutant cell line in which uptake of fluorescent PS analogs was reduced to about 25% of the wild type level at either pH 6.0 or 7.4. Control experiments demonstrated that the reduced uptake of fluorescent PS analogs in the mutant cells was unrelated to multidrug resistance, and that endocytosis of another plasma membrane lipid marker occurred normally in the mutant cells. These results suggested that a non-endocytic pathway responsible for uptake of fluorescent PS analogs was specifically affected in the mutant cells. PMID- 7876306 TI - A posttranslational modification of beta-actin contributes to the slow dissociation of the spectrin-protein 4.1-actin complex of irreversibly sickled cells. AB - Irreversibly sickled cells (ISCs) remain sickled even under conditions where they are well oxygenated and hemoglobin is depolymerized. In our studies we demonstrate that triton extracted ISC core skeletons containing only spectrin, protein 4.1, and actin also retain their sickled shape; while reversibly sickled cell (RSC) skeletons remodel to a round or biconcave shape. We also demonstrate that these triton extracted ISC core skeletons dissociate more slowly upon incubation at 37 degrees C than do RSC or control (AA) core skeletons. This observation may supply the basis for the inability of the ISC core skeleton to remodel its shape. Using an in vitro ternary complex dissociation assay, we demonstrate that a modification in beta-actin is the major determinant of the slow dissociation of the spectrin-protein 4.1-actin complex isolated from the ISC core skeleton. We demonstrate that the difference between ISC and control beta actin is the inaccessibility of two cysteine residues in ISC beta-actin to labeling by thiol reactive reagents; due to the formation of a disulfide bridge between cysteine284 and cysteine373 in ISC beta-actin, or alternatively another modification of cysteine284 and cysteine373 which is reversible with DTT and adds less than 100 D to the molecular weight of beta-actin. PMID- 7876307 TI - Genetic deletion of ABP-120 alters the three-dimensional organization of actin filaments in Dictyostelium pseudopods. AB - This study extends the observations on the defects in pseudopod formation of ABP 120+ and ABP-120- cells by a detailed morphological and biochemical analysis of the actin based cytoskeleton. Both ABP-120+ and ABP-120- cells polymerize the same amount of F-actin in response to stimulation with cAMP. However, unlike ABP 120+ cells, ABP-120- cells do not incorporate actin into the Triton X-100 insoluble cytoskeleton at 30-50 s, the time when ABP-120 is incorporated into the cytoskeleton and when pseudopods are extended after cAMP stimulation in wild-type cells. By confocal and electron microscopy, pseudopods extended by ABP-120- cells are not as large or thick as those produced by ABP-120+ cells and in the electron microscope, an altered filament network is found in pseudopods of ABP-120- cells when compared to pseudopods of ABP-120+ cells. The actin filaments found in areas of pseudopods in ABP-120+ cells either before or after stimulation were long, straight, and arranged into space filling orthogonal networks. Protrusions of ABP 120- cells are less three-dimensional, denser, and filled with multiple foci of aggregated filaments consistent with collapse of the filament network due to the absence of ABP-120-mediated cross-linking activity. The different organization of actin filaments may account for the diminished size of protrusions observed in living and fixed ABP-120- cells compared to ABP-120+ cells and is consistent with the role of ABP-120 in regulating pseudopod extension through its cross-linking of actin filaments. PMID- 7876308 TI - Indirect association of ezrin with F-actin: isoform specificity and calcium sensitivity. AB - Whereas it has been demonstrated that muscle and nonmuscle isoactins are segregated into distinct cytoplasmic domains, the mechanism regulating subcellular sorting is unknown (Herman, 1993a). To reveal whether isoform specific actin-binding proteins function to coordinate these events, cell extracts derived from motile (Em) versus stationary (Es) cytoplasm were selectively and sequentially fractionated over filamentous isoactin affinity columns prior to elution with a KCl step gradient. A polypeptide of interest, which binds specifically to beta-actin filament columns, but not to muscle actin columns has been conclusively identified as the ERM family member, ezrin. We studied ezrin-beta interactions in vitro by passing extracts (Em) over isoactin affinity matrices in the presence of Ca(2+)-containing versus Ca(2+)-free buffers, with or without cytochalasin D. Ezrin binds and can be released from beta-actin Sepharose-4B in the presence of Mg2+/EGTA and 100 mM NaCl (at 4 degrees C and room temperature), but not when affinity fractionation of Em is carried out in the presence of 0.2 mM CaCl2 or 2 microM cytochalasin D. N-acetyl (leucyl)2-norleucinal and E64, two specific inhibitors of the calcium-activated protease, calpain I, protect ezrin binding to beta actin in the presence of calcium. Moreover, biochemical analysis of endothelial lysates reveals that a calpain I cleavage product of ezrin emerges when cell locomotion is stimulated in response to monolayer injury. Immunofluorescence analysis of leading lamellae reveals that anti-ezrin and anti-beta-actin IgGs can be simultaneously co localized, extending the results of isoactin affinity fractionation of Em-derived extracts and suggesting that ezrin and beta-actin interact in vivo. To test the hypothesis that ezrin binds directly to beta-actin, we performed three sets of studies under a wide range of physiological conditions (pH 7.0-8.5) using purified pericyte ezrin and either alpha- or beta-actin. These included co sedimentation, isoactin affinity fractionation, and co-immunoprecipitation. Results of these experiments reveal that purified ezrin does not directly bind to beta-actin filaments, either in solution or while isoactins are covalently cross linked to Sepharose-4B. This is in contrast to our finding that ezrin and beta actin could be co-immunoprecipitated or co-sedimented from Em-derived cell lysates. To explore whether calcium transients occur in cellular domains enriched in ezrin and beta-actin, we mapped cellular free calcium in endothelial monolayers crawling in response to injury.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7876309 TI - Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets p34cdc2 kinase to microtubules and is a potential regulator of M-phase microtubule dynamics. AB - We previously demonstrated (Ookata et al., 1992, 1993) that the p34cdc2/cyclin B complex associates with microtubules in the mitotic spindle and premeiotic aster in starfish oocytes, and that microtubule-associated proteins (MAPs) might be responsible for this interaction. In this study, we have investigated the mechanism by which p34cdc2 kinase associates with the microtubule cytoskeleton in primate tissue culture cells whose major MAP is known to be MAP4. Double staining of primate cells with anti-cyclin B and anti-MAP4 antibodies demonstrated these two antigens were colocalized on microtubules and copartitioned following two treatments that altered MAP4 distribution. Detergent extraction before fixation removed cyclin B as well as MAP4 from the microtubules. Depolymerization of some of the cellular microtubules with nocodazole preferentially retained the microtubule localization of both cyclin B and MAP4. The association of p34cdc2/cyclin B kinase with microtubules was also shown biochemically to be mediated by MAP4. Cosedimentation of purified p34cdc2/cyclin B with purified microtubule proteins containing MAP4, but not with MAP-free microtubules, as well as binding of MAP4 to GST-cyclin B fusion proteins, demonstrated an interaction between cyclin B and MAP4. Using recombinant MAP4 fragments, we demonstrated that the Pro-rich C-terminal region of MAP4 is sufficient to mediate the cyclin B-MAP4 interaction. Since p34cdc2/cyclin B physically associated with MAP4, we examined the ability of the kinase complex to phosphorylate MAP4. Incubation of a ternary complex of p34cdc2, cyclin B, and the COOH-terminal domain of MAP4, PA4, with ATP resulted in intracomplex phosphorylation of PA4. Finally, we tested the effects of MAP4 phosphorylation on microtubule dynamics. Phosphorylation of MAP4 by p34cdc2 kinase did not prevent its binding to microtubules, but abolished its microtubule stabilizing activity. Thus, the cyclin B/MAP4 interaction we have described may be important in targeting the mitotic kinase to appropriate cytoskeletal substrates, for the regulation of spindle assembly and dynamics. PMID- 7876310 TI - The Cdc31p-binding protein Kar1p is a component of the half bridge of the yeast spindle pole body. AB - KAR1 has been identified as an essential gene which is involved in karyogamy of mating yeast cells and in spindle pole body duplication of mitotic cells (Rose, M. D., and G. R. Fink. 1987. Cell. 48:1047-1060). We investigated the cell cycle dependent localization of the Kar1 protein (Kar1p) and its interaction with other SPB components. Kar1p is associated with the spindle pole body during the entire cell cycle of yeast. Immunoelectron microscopic studies with anti-Kar1p antibodies or with the monoclonal antibody 12CA5 using an epitope-tagged, functional Kar1p revealed that Kar1p is associated with the half bridge or the bridge of the spindle pole body. Cdc31p, a Ca(2+)-binding protein, was previously identified as the first component of the half bridge of the spindle pole body (Spang, A., I. Courtney, U. Fackler, M. Matzner, and E. Schiebel. 1993. J. Cell Biol. 123:405-416). Using an in vitro assay we demonstrate that Cdc31p specifically interacts with a short sequence within the carboxyl terminal half of Kar1p. The potential Cdc31p-binding sequence of Kar1p contains three acidic amino acids which are not found in calmodulin-binding peptides, explaining the different substrate specificities of Cdc31p and calmodulin. Cdc31p was also able to bind to the carboxy terminus of Nuflp/Spc110p, another component of the SPB (Kilmartin, J. V., S. L. Dyos, D. Kershaw, and J. T. Finch. 1993. J. Cell Biol. 123:1175-1184). The association of Kar1p with the spindle pole body was independent of Cdc31p. Cdc31p, on the other hand, was not associated with SPBs of kar1 cells. PMID- 7876311 TI - Protein phosphatase 1 regulates the cytoplasmic dynein-driven formation of endoplasmic reticulum networks in vitro. AB - Interphase Xenopus egg extracts form extensive tubular membrane networks in vitro. These networks are identified here as endoplasmic reticulum by the presence of ER resident proteins, as shown by immunofluorescence, and by the presence of single ribosomes and polysomes, as shown by electron microscopy. The effect of phosphorylation on ER movement in interphase was tested using the phosphatase inhibitor, okadaic acid. Okadaic acid treatment resulted in an increase of up to 27-fold in the number of ER tubules moving and in the extent of ER networks formed compared to control extracts. This activation was blocked by the broad-specificity kinase inhibitor 6-dimethylaminopurine. Okadaic acid had no effect, however, on the direction of ER tubule movement, which occurred towards the minus end of microtubules, and was sensitive to low concentrations of vanadate. Inhibition of phosphatases also had no effect on the speed or duration of ER tubule extensions, and did not stimulate the activity of soluble cytoplasmic dynein. The sensitivity of ER movement to okadaic acid closely matched that of protein phosphatase 1. Although the amount of ER motility was greatly increased by inhibiting protein phosphatase 1 (PP1), the amount of cytoplasmic dynein associated with the membrane was not altered. The data support a model in which phosphorylation regulates ER movement by controlling the activity of cytoplasmic dynein bound to the ER membrane. PMID- 7876313 TI - Dephosphorylated synapsin I anchors synaptic vesicles to actin cytoskeleton: an analysis by videomicroscopy. AB - Synapsin I is a synaptic vesicle-associated protein which inhibits neurotransmitter release, an effect which is abolished upon its phosphorylation by Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). Based on indirect evidence, it was suggested that this effect on neurotransmitter release may be achieved by the reversible anchoring of synaptic vesicles to the actin cytoskeleton of the nerve terminal. Using video-enhanced microscopy, we have now obtained experimental evidence in support of this model: the presence of dephosphorylated synapsin I is necessary for synaptic vesicles to bind actin; synapsin I is able to promote actin polymerization and bundling of actin filaments in the presence of synaptic vesicles; the ability to cross-link synaptic vesicles and actin is specific for synapsin I and is not shared by other basic proteins; the cross-linking between synaptic vesicles and actin is specific for the membrane of synaptic vesicles and does not reflect either a non-specific binding of membranes to the highly surface active synapsin I molecule or trapping of vesicles within the thick bundles of actin filaments; the formation of the ternary complex is virtually abolished when synapsin I is phosphorylated by CaM kinase II. The data indicate that synapsin I markedly affects synaptic vesicle traffic and cytoskeleton assembly in the nerve terminal and provide a molecular basis for the ability of synapsin I to regulate the availability of synaptic vesicles for exocytosis and thereby the efficiency of neurotransmitter release. PMID- 7876312 TI - The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues. AB - Ryanodine receptors (RyRs) are intracellular calcium release channels that participate in controlling cytosolic calcium levels. At variance with the probably ubiquitous inositol 1,4,5-trisphosphate-operated calcium channels (1,4,5 trisphosphate receptors), RyRs have been mainly regarded as the calcium release channels controlling skeletal and cardiac muscle contraction. Increasing evidence has recently suggested that RyRs may be more widely expressed, but this has never been extensively examined. Therefore, we cloned three cDNAs corresponding to murine RyR homologues to carry a comprehensive analysis of their expression in murine tissues. Here, we report that the three genes are expressed in almost all tissues analyzed, where tissue-specific patterns of expression were observed. In the uterus and vas deferens, expression of RyR3 was localized to the smooth muscle component of these organs. In the testis, expression of RyR1 and RyR3 was detected in germ cells. RyR mRNAs were also detected in in vitro-cultured cell lines. RyR1, RyR2, and RyR3 mRNA were detected in the cerebrum and in the cerebellum. In situ analysis revealed a cell type-specific pattern of expression in the different regions of the central nervous system. The differential expression of the three ryanodine receptor genes in the central nervous system was also confirmed using specific antibodies against the respective proteins. This widespread pattern of expression suggests that RyRs may participate in the regulation of intracellular calcium homeostasis in a range of cells wider than previously recognized. PMID- 7876314 TI - Axonal synthesis of phosphatidylcholine is required for normal axonal growth in rat sympathetic neurons. AB - The goal of this study was to assess the relative importance of the axonal synthesis of phosphatidylcholine for neurite growth using rat sympathetic neurons maintained in compartmented culture dishes. In a double-labeling experiment [14C]choline was added to compartments that contained only distal axons and [3H]choline was added to compartments that contained cell bodies and proximal axons. The specific radioactivity of labeled choline was equalized in all compartments. The results show that approximately 50% of phosphatidylcholine in distal axons is locally synthesized by axons. The requirement of axonal phosphatidylcholine synthesis for neurite growth was investigated. The neurons were supplied with medium lacking choline, an essential substrate for phosphatidylcholine synthesis. In the cells grown in choline-deficient medium for 5 d, the incorporation of [3H]palmitate into phosphatidylcholine was reduced by 54% compared to that in cells cultured in choline-containing medium. When phosphatidylcholine synthesis was reduced in this manner in distal axons alone, growth of distal neurites was inhibited by approximately 50%. In contrast, when phosphatidylcholine synthesis was inhibited only in the compartment containing cell bodies with proximal axons, growth of distal neurites continued normally. These experiments imply that the synthesis of phosphatidylcholine in cell bodies is neither necessary nor sufficient for growth of distal neurites. Rather, the local synthesis of phosphatidylcholine in distal axons is required for normal growth. PMID- 7876315 TI - Downregulation of amyloid precursor protein inhibits neurite outgrowth in vitro. AB - The amyloid precursor protein (APP) is a transmembrane protein expressed in several cell types. In the nervous system, APP is expressed by glial and neuronal cells, and several lines of evidence suggest that it plays a role in normal and pathological phenomena. To address the question of the actual function of APP in normal developing neurons, we undertook a study aimed at blocking APP expression using antisense oligonucleotides. Oligonucleotide internalization was achieved by linking them to a vector peptide that translocates through biological membranes. This original technique, which is very efficient and gives direct access to the cell cytosol and nucleus, allowed us to work with extracellular oligonucleotide concentrations between 40 and 200 nM. Internalization of antisense oligonucleotides overlapping the origin of translation resulted in a marked but transient decrease in APP neosynthesis that was not observed with the vector peptide alone, or with sense oligonucleotides. Although transient, the decrease in APP neosynthesis was sufficient to provoke a distinct decrease in axon and dendrite outgrowth by embryonic cortical neurons developing in vitro. The latter decrease was not accompanied by changes in the spreading of the cell bodies. A single exposure to coupled antisense oligonucleotides at the onset of the culture was sufficient to produce significant morphological effects 6, 18, and 24 h later, but by 42 h, there were no remaining significant morphologic changes. This report thus demonstrates that amyloid precursor protein plays an important function in the morphological differentiation of cortical neurons in primary culture. PMID- 7876316 TI - The membrane protein CD9/DRAP 27 potentiates the juxtacrine growth factor activity of the membrane-anchored heparin-binding EGF-like growth factor. AB - The membrane-anchored heparin-binding EGF-like growth factor precursor (proHB EGF)/diphtheria toxin receptor (DTR) belongs to a class of transmembrane growth factors and physically associates with CD9/DRAP27 which is also a transmembrane protein. To evaluate the biological activities of proHB-EGF/DTR as a juxtacrine growth factor and the biological significance of its association with CD9/DRAP27, the mitogenic activity of proHB-EGF/DTR was analyzed using stable transfectants of mouse L cells expressing both human proHB-EGF/DTR and monkey CD9/DRAP27, or either one alone. Juxtacrine activity was assayed by measuring the ability of cells in co-culture to stimulate DNA synthesis in an EGF receptor ligand dependent cell line, EP170.7. LH-2 cells expressing human proHB-EGF/DTR stimulated EP170.7 cell growth moderately. However, LCH-1 cells, a stable co transfectant expressing both human proHB-EGF/DTR and monkey CD9/DRAP27 cDNAs, dramatically unregulated the juxtacrine growth factor activity of proHB-EGF/DTR approximately 25 times over that of LH-2 cells even though both cell types expressed similar levels of proHB-EGF/DTR on the cell surface. Anti-CD9/DRAP27 antibodies which were not able to neutralize the mitogenic activity of soluble HB EGF suppressed LCH-1 cell juxtacrine growth activity to the same extent as did anti-HB-EGF neutralizing antibodies and CRM 197, specific inhibitors of human HG EGF. These findings suggest that optimal expression of the juxtacrine growth activity of proHB-EGF/DTR requires co-expression of CD9/DRAP27. These studies also indicate that growth factor potentiation effects which have been observed previously for soluble growth factors also occurs at the level of cell surface associated growth factors. PMID- 7876317 TI - Intracellular domain of desmoglein 3 (pemphigus vulgaris antigen) confers adhesive function on the extracellular domain of E-cadherin without binding catenins. AB - For the extracellular (EC) domain of E-cadherin to function in homophilic adhesion it is thought that its intracytoplasmic (IC) domain must bind alpha- and beta-catenins, which link it to the actin cytoskeleton. However, the IC domain of pemphigus vulgaris antigen (PVA or Dsg3), which is in the desmoglein subfamily of the cadherin gene superfamily, does not bind alpha- or beta-catenins. Because desmogleins have also been predicted to function in the cell adhesion of desmosomes, we speculated that the PVA IC domain might be able to act in a novel way in conferring adhesive function on the EC domain of cadherins. To test this hypothesis we studied aggregation of mouse fibroblast L cell clones that expressed chimeric cDNAs encoding the EC domain of E-cadherin with various IC domains. We show here that the full IC domain of PVA as well as an IC subdomain containing only 40 amino acids of the PVA intracellular anchor (IA) region confer adhesive function on the E-cadherin EC domain without catenin-like associations with cytoplasmic molecules or fractionation with the cell cytoskeleton. This IA region subdomain is evolutionarily conserved in desmogleins, but not classical cadherins. These findings suggest an important cell biologic function for the IA region of desmogleins and demonstrate that strong cytoplasmic interactions are not absolutely necessary for E-cadherin-mediated adhesion. PMID- 7876318 TI - Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes. AB - p120 was originally identified as a substrate of pp60src and several receptor tyrosine kinases, but its function is not known. Recent studies revealed that this protein shows homology to a group of proteins, beta-catenin/Armadillo and plakoglobin (gamma-catenin), which are associated with the cell adhesion molecules cadherins. In this study, we examined whether p120 is associated with E cadherin using the human carcinoma cell line HT29, as well as other cell lines, which express both of these proteins. When proteins that copurified with E cadherin were analyzed, not only alpha-catenin, beta-catenin, and plakoglobin but also p120 were detected. Conversely, immunoprecipitates of p120 contained E cadherin and all the catenins, although a large subpopulation of p120 was not associated with E-cadherin. Analysis of these immunoprecipitates suggests that 20% or less of the extractable E-cadherin is associated with p120. When p120 immunoprecipitation was performed with cell lysates depleted of E-cadherin, beta catenin was no longer coprecipitated, and the amount of plakoglobin copurified was greatly reduced. This finding suggests that there are various forms of p120 complexes, including p120/E-cadherin/beta-catenin and p120/E-cadherin/plakoglobin complexes; this association profile contrasts with the mutually exclusive association of beta-catenin and plakoglobin with cadherins. When the COOH terminal catenin binding site was truncated from E-cadherin, not only beta catenin but also p120 did not coprecipitate with this mutated E-cadherin. Immunocytological studies showed that p120 colocalized with E-cadherin at cell cell contact sites, even after non-ionic detergent extraction. Treatment of cells with hepatocyte growth factor/scatter factor altered the level of tyrosine phosphorylation of p120 as well as of beta-catenin and plakoglobin. These results suggest that p120 associates with E-cadherin at its COOH-terminal region, but the mechanism for this association differs from that for the association of beta catenin and plakoglobin with E-cadherin, and thus, that p120, whose function could be modulated by growth factors, may play a unique role in regulation of the cadherin-catenin adhesion system. PMID- 7876320 TI - Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. AB - Bone formation in the embryo, and during adult fracture repair and remodeling, involves the progeny of a small number of cells called mesenchymal stem cells (MSCs). These cells continuously replicate themselves, while a portion become committed to mesenchymal cell lineages such as bone, cartilage, tendon, ligament, and muscle. The differentiation of these cells, within each lineage, is a complex multistep pathway involving discrete cellular transitions much like that which occurs during hematopoiesis. Progression from one stage to the next depends on the presence of specific bioactive factors, nutrients, and other environmental cues whose exquisitely controlled contributions orchestrate the entire differentiation phenomenon. An understanding of the cellular and molecular events of osteogenic differentiation of MSCs provides the foundation for the emergence of a new therapeutic technology for cell therapy. The isolation and in vitro mitotic expansion of autologous human MSCs will support the development of novel protocols for the treatment of many clinically challenging conditions. For example, local bone defects can be repaired through site-directed delivery of MSCs in an appropriate carrier vehicle. Generalized conditions, such as osteoporosis, may be treatable by systemic administration of culture-expanded autologous MSCs or through biopharmaceutical regimens based on the discovery of critical regulatory molecules in the differentiation process. With this in mind, we can begin to explore therapeutic options that have never before been available. PMID- 7876319 TI - Embryonic axis induction by the armadillo repeat domain of beta-catenin: evidence for intracellular signaling. AB - beta-catenin was identified as a cytoplasmic cadherin-associated protein required for cadherin adhesive function (Nagafuchi, A., and M. Takeichi. 1989. Cell Regul. 1:37-44; Ozawa, M., H. Baribault, and R. Kemler. 1989. EMBO [Eur. Mol. Biol. Organ.] J. 8:1711-1717). Subsequently, it was found to be the vertebrate homologue of the Drosophila segment polarity gene product Armadillo (McCrea, P. D., C. W. Turck, and B. Gumbiner. 1991. Science [Wash. DC]. 254:1359-1361; Peifer, M., and E. Wieschaus. 1990. Cell. 63:1167-1178). Also, antibody perturbation experiments implicated beta-catenin in axial patterning of the early Xenopus embryo (McCrea, P. D., W. M. Brieher, and B. M. Gumbiner. 1993. J. Cell Biol. 123:477-484). Here we report that overexpression of beta-catenin in the ventral side of the early Xenopus embryo, by injection of synthetic beta-catenin mRNA, induces the formation of a complete secondary body axis. Furthermore, an analysis of beta-catenin deletion constructs demonstrates that the internal armadillo repeat region is both necessary and sufficient to induce axis duplication. This region interacts with C-cadherin and with the APC tumor suppressor protein, but not with alpha-catenin, that requires the amino-terminal region of beta-catenin to bind to the complex. Since alpha-catenin is required for cadherin-mediated adhesion, the armadillo repeat region alone probably cannot promote cell adhesion, making it unlikely that beta-catenin induces axis duplication by increasing cell adhesion. We propose, rather, that beta-catenin acts in this circumstance as an intracellular signaling molecule. Subcellular fractionation demonstrated that all of the beta-catenin constructs that contain the armadillo repeat domain were present in both the soluble cytosolic and the membrane fraction. Immunofluorescence staining confirmed the plasma membrane and cytoplasmic localization of the constructs containing the armadillo repeat region, but revealed that they also accumulate in the nucleus, especially the construct containing only the armadillo repeat domain. These findings and the beta-catenin protein interaction data offer several intriguing possibilities for the site of action or the protein targets of beta-catenin signaling activity. PMID- 7876321 TI - Mechanisms of glucocorticoid action in bone cells. AB - Glucocorticoids play an important role in the normal regulation of bone remodeling; however continued exposure of bone to glucocorticoid excess results in osteoporosis. In vivo, glucocorticoids stimulate bone resorption and decrease bone formation, and in vitro studies have shown that while glucocorticoids stimulate osteoblastic differentiation, they have important inhibitory actions on bone formation. Glucocorticoids have many effects on osteoblast gene expression, including down-regulation of type I collagen and osteocalcin, and up-regulation of interstitial collagenase. The synthesis and activity of osteoblast growth factors can be modulated by glucocorticoids as well. For example, insulin-like growth factor I (IGF-I) is an important stimulator of osteoblast function, and expression of IGF-I is decreased by glucocorticoids. The activity of IGF I can be modified by IGF binding proteins (IGFBPs), and their synthesis is also regulated by glucocorticoids. Thus, glucocorticoid action on osteoblasts can be direct, by activating or repressing osteoblast gene expression, or indirect by altering the expression or activity of osteoblast growth factors. Further investigation of the mechanisms by which glucocorticoids modulate gene expression in bone cells will contribute to our understanding of steroid hormone biology and will provide a basis for the design of effective treatments for glucocorticoid-induced osteoporosis. PMID- 7876322 TI - Nongenomic actions of the steroid hormone 1 alpha,25-dihydroxyvitamin D3. AB - Recent studies indicate that the vitamin D hormone, 1 alpha,25-dihydroxyvitamin D3 exerts rapid effects (seconds to minutes) in a variety of cell types. These rapid nongenomic actions in osteoblasts include effects on membrane voltage-gated calcium channels, phospholipase C activity, and the sodium/hydrogen antiport. Since the rapid effects occur in osteoblasts that lack the nuclear vitamin D receptor, it is postulated that the nongenomic responses to the hormone reflect interaction with a separate, membrane localized signalling system. Preliminary studies demonstrate the presence of a receptor on the membranes of osteoblasts that lack the nuclear vitamin D receptor. This membrane receptor recognizes 1 alpha,25-dihydroxyvitamin D3 and its inaction 1 beta epimer, but not 25 hydroxyvitamin D3. These rapid nongenomic actions generated by interaction with the membrane receptor modulate the effects of the hormone on gene transcription. Thus, the rapid nongenomic pathway may play a regulatory function in modulating the genomic pathways affected by 1 alpha,25-dihydroxyvitamin D3. PMID- 7876323 TI - Vitamin D receptor alleles and bone physiology. AB - The vitamin D endocrine system is central to the control of bone and calcium homeostasis. The active hormonal form of vitamin D, 1,25 dihydroxyvitamin D (calcitriol), the circulating level of which is tightly regulated, acts through a specific receptor to mediate its genomic actions on almost every aspect of calcium homeostasis. Because of its transactivation function, it is possible that a small difference in vitamin D receptor level could be amplified into a biologically significant alteration in physiological setpoint. The recent finding that polymorphisms in the vitamin D receptor gene are predictive of bone density (Morrison et al., Nature 367:284-287, 1994) is the first example of an allelic effect in such a homeostatically controlled system. This raises the possibility that such central operators may exist in other regulatory pathways, and could explain a large part of the observed "normal" population distribution that exists for all physiological parameters. PMID- 7876324 TI - Understanding bone cell biology requires an integrated approach: reliable opportunities to study osteoclast biology in vivo. AB - The relative simplicity of all in vitro methods to study bone cell biology will at best result in oversimplification of the development and functional capacity of the skeleton in vivo. We have shown this to be true for selected aspects of bone cell biology, but numerous other examples are available. One alternative is to undertake skeletal research in vivo. It is important that those in bone research be willing to move increasingly in this direction not only to understand the true complexities of skeletal versatility, but also to avoid repetition and perpetuation of erroneous or irrelevant conclusions which waste resources. Toward this end we have described two situations, osteopetrosis and tooth eruption, in which reproducible abrogations or local activations of bone resorption can be examined in vivo. The application of emerging molecular and morphological techniques that permit the subcellular dissection of metabolic pathways and their precise cellular localization, such as a combination of the variety of in situ hybridization technologies with PCR, antisense probes, and antibody blockase, will allow the investigator greater control of variables in vivo. We expect that these technologies, largely worked out in vitro, combined with highly selected, appropriate models, as we have ourlined here for osteoclast biology, will make research in vivo less intimidating and increase the frequency with which the real biology is studied directly. PMID- 7876325 TI - Blockade of osteoclast-mediated bone resorption through occupancy of the integrin receptor: a potential approach to the therapy of osteoporosis. AB - Bone resorption requires the tight attachment of the bone-resorbing cells, the osteoclasts, to the bone mineralized matrix. Integrins, a class of cell surface adhesion glycoproteins, play a key role in the attachment process. Most integrins bind to their ligands via the arginyl-glycyl-aspartyl (R-G-D) tripeptide present within the ligand sequence. The interaction between integrins and ligands results in bidirectional transfer of signals across the plasma membrane. Tyrosine phosphorylation occurs within cells as a result of integrin binding to ligands and probably plays a role in the formation of the osteoclast clear zone, a specialized region of the osteoclast membrane maintained by cytoskeletal structure and involved in bone resorption. Human osteoclasts express alpha 2 beta 1 and alpha v beta 3 integrins on their surface. Such signaling may also lead to "inside-out" effects, like increased expression of integrin receptors on the cell surface, or increased affinity of the integrin to its ligand. The alpha v beta 3 integrin, a vitronectin receptor, plays an essential role in bone resorption. Antibodies to this integrin and short synthetic RGD-containing peptides are able to block bone resorption in vitro. Echistatin, an RGD-containing protein from a snake venom, binds to the alpha v beta 3 integrin and blocks bone resorption both in vitro and in vivo. Peptides containing the RGD motif are potential competitive "antagonists" of the osteoclast integrins and may have utility in the blockade of bone resorption. Agonists may be identified by stimulation of intracellular signaling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876326 TI - Nongenomic regulation of extracellular matrix events by vitamin D metabolites. AB - Vitamin D metabolites appear to regulate chondrocytes and osteoblasts via a combination of genomic and nongenomic mechanisms. Specificity of the nongenomic response to either 1,25-(OH)2D3 or 24,25-(OH)2D3 may be conferred by the chemical composition of the target membrane and its fluid mosaic structure, by the presence of specific membrane receptors, or by the interaction with classic vitamin D receptors. Nongenomic effects have been shown to include changes in membrane fluidity, fatty acid acylation and reacylation, arachidonic acid metabolism and prostaglandin production, calcium ion flux, and protein kinase C activity. Chondrocytes metabolize 25-(OH)D3 to 1,25-(OH)2D3 and 24,25-(OH)2D3; production of these metabolites is regulated by both growth factors and hormones and is dependent on the state of cell maturation. 1,25-(OH)2D3 and 24,25-(OH)2D3 may interact directly with extracellular matrix vesicles to regulate their function in the matrix, including protease activity, resulting in matrix modification and calcification. Isolated matrix vesicles, produced by growth zone chondrocytes, can activate latent transforming growth factor-beta when incubated with exogenous 1,25-(OH)2D3. These observations suggest that nongenomic regulation of matrix vesicle structure and function may be a mechanism by which mesenchymal cells, like osteoblasts and chondrocytes, may modulate events in the extracellular matrix at sites distant from the cell surface. PMID- 7876327 TI - Underlying mechanisms at the bone-biomaterial interface. AB - In order to understand how biomaterials influence bone formation in vivo, it is necessary to examine cellular response to materials in the context of wound healing. Four interrelated properties of biomaterials (chemical composition, surface energy, surface roughness, and surface topography) affect mesenchymal cells in vitro. Attachment, proliferation, metabolism, matrix synthesis, and differentiation of osteoblast-like cell lines and primary chondrocytes are sensitive to one or more of these properties. The nature of the response depends on cell maturation state. Rarely do differentiated osteoblasts or chondrocytes see a material prior to its modification by biological fluids, immune cells and less differentiated mesenchymal cells in vivo. Studies using the rat marrow ablation model of endosteal wound healing indicate that ability of osteoblasts to synthesize and calcify their extracellular matrix is affected by the local presence of the material. Changes in the morphology and biochemistry of matrix vesicles, extracellular organelles associated with matrix maturation and calcification, seen in normal endosteal healing, are altered by implants. Moreover, the material exerts a systemic effect on endosteal healing as well. This may be due to local effects on growth factor production and secretion into the circulation, as well as to the fact that the implant may serve as a bioreactor. PMID- 7876328 TI - Growth hormone, insulin-like growth factors, and the senescent skeleton: Ponce de Leon's Fountain revisited? AB - As the population ages, the prevalence of osteoporosis will continue to rise. Yet, the mechanisms leading to age-related bone loss remain poorly defined. Furthermore, extensive longitudinal studies of bone mass, especially in the three decades beyond menopause, have not been completed. Although calciotropic hormones, growth hormone (GH), and insulin-like growth factor-I (IGF-I) change with age, it is not certain if these changes are responsible for age-related bone loss. Nor is it clear if the "senescent" osteoblast is fully responsive to growth factor stimulation. To complicate matters further, both circulatory and skeletal IGF regulatory systems are extremely redundant. Changes in serum IGFs may lead to compensatory alterations in IGF receptor number, IGF binding protein (IGFBP) synthesis, or IGFBP catabolism. What is measured in serum, may, in the end, be either a mirror or a mirage of skeletal IGF action! Clinical trials with "replacement" doses of GH or IGF-I are underway. But, critical evidence does not yet support the concept that a true "sommatopause" alters bone remodeling. Moreover, only scarce data exist that GH augments bone formation or prevents bone loss in the elderly. As clinicians expand the use of recombinant growth factors to elders, ethical and clinical issues surrounding administration of the new "fountain of youth" will be revisited. For basic scientists studying skeletal growth factors and their relationship to senescence, significant questions remain unanswered. New technological advances will provide clues about the basic mechanisms of skeletal aging.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876329 TI - Mechanisms by which cells of the osteoblast lineage control osteoclast formation and activity. AB - The cells of bone are of two lineages, the osteoblasts arising from pluripotential mesenchymal cells and osteoclasts from hemopoietic precursors of the monocyte-macrophage series. Resorption of bone by the multinucleate osteoclast requires the generation of new osteoclasts and their activation. Many hormones and cytokines are able to promote bone resorption by influencing these processes, but they achieve this without acting directly on osteoclasts. Most evidence indicates that their actions are mediated by cells of the osteoblast lineage. Evidence for hormone- and cytokine-induced activation of osteoclasts requiring the mediation of osteoblasts comes from studies of resorption by isolated osteoclasts. However, consistent evidence for a specific "activating factor" is lacking, and the argument is presented that the isolated osteoclast resorption assays have not been shown convincingly to be assays of osteoclast activation. The view is presented that osteoblast-mediated osteoclast activation is the result of several events in the microenvironment without necessarily requiring the existence of a specific, essential osteoclast activator. On the other hand, a specific promoter of osteoclast differentiation does seem likely to be a product of cells of the stromal/osteoblast series. Evidence in favour of this comes from studies of osteoclast generation in co-cultures of osteoblast/stromal cells with hemopoietic cells. Conflicting views, maintaining that osteoclasts can develop from hemopoietic cells without stromal intervention, might be explained by varying criteria used in identification of osteoclasts. Osteoblastic and osteoclastic renewal, and the interactions of these lineages, are central to the process of bone remodeling. PMID- 7876330 TI - Osteoclast radicals. AB - In biological research, new ideas arise and quickly spread to encompass the entire field. Thus, the evolution of molecular biology has significantly changed our methods of approaching our research. A similar far-reaching finding has been the advent of radical reactions into biology. Although radical chemistry has been utilized for many technological advances that affect our daily lives, the appreciation of this same process within our cells has opened an unexplored arena for research enquiry. As cellular messengers, radical molecules seem whimsically designed: they are evanescent, rapidly and apparently indiscriminately reactive, and barely detectable by most biological methods. Yet, our initial probing of these reactive agents in cells and organisms has led us to postulate a virtually undescribed system of communication within and among cells which may have significant effects in multiple organs. In bone, radical reactants have been attributed with an important role in the control of bone resorption. PMID- 7876331 TI - Myeloblastic cell line expresses osteoclastic properties following coculture with marrow stromal adipocytes. AB - Osteoclasts are derived from hemopoietic precursors in the marrow. Their differentiation pathway is still undefined, but an important role was observed for the marrow microenvironment in the regulation of osteoclastogenesis. Various marrow stromal cell subtypes were used to study their possible role in the formation of osteoclasts from myeloblast (M1) cells. Interactions between M1 cells and the 14F1.1 endothelial-adipocyte stromal cell line were demonstrated in a coculture model. M1 cells attached to the adherent layer of 14F1.1 cells and formed distinct foci reminiscente of "cobblestone areas." Following these interactions, M1 cells developed specific enzymatic activities and became multinucleated. Both mononuclear and multinuclear M1 cells became positive to tartrate-resistant acid phosphatase (TRaP) and ATPase, a feature characteristic of osteoclasts, and were also responsive to calcitonin. Furthermore, they attached to mineralized bone particles and their membrane changed into a ruffled border at the zone of interaction with the bone matrix. We thus demonstrated that marrow endothelial-adipocytes may play a role in regulating the differentiation of myeloblasts into osteoclasts. PMID- 7876332 TI - Characterization of the major sulfated protein of mouse pancreatic acinar cells: a high molecular weight peripheral membrane glycoprotein of zymogen granules. AB - The major sulfated protein of the mouse pancreatic acinar cell, gp300, has been identified and characterized with monoclonal and polyclonal antibodies. gp300 is a glycoprotein of M(r) = 300,000 which contains approximately 40% of metabolically incorporated [35S]sulfate in the acinar cell. Sulfate on gp300 is resistant to hot 1N HCl, but sensitive to alkaline hydrolysis, demonstrating that the sulfate is carbohydrate-linked rather than tyrosine-linked. gp300 metabolically labeled with [3H]glucosamine and [35S]sulfate was chemically and enzymatically treated followed by Bio-Gel P-10 gel filtration. Both labels were resistant to treatments which degrade glycosaminoglycans. Treatment of dual labeled gp300 with PNGase F to cleave N-linked oligosaccharides released approximately 17% of [3H] and little [35S]. Mild alkaline borohydride treatment after removal of N-linked sugar released the remainder of both labels, indicating the presence of sulfated O-linked oligosaccharides. Biosynthesis studies and PNGase F digestion indicate that the core protein is approximately 210 kDa, with apparent contributions of approximately 35 kDa N-linked sugar, and approximately 55 kDa O-linked sugar. Lectin blotting and glycosidase digestion demonstrated the presence of Gal beta(1-3)GalNAc and sialic acid alpha(2-3)Gal in O-linked oligosaccharide, and Gal beta(1-4)GlcNAc in N-linked oligosaccharide. Immunolocalization and subcellular fractionation showed that gp300 is a peripheral membrane protein localized to the lumenal face of the zymogen granule membrane. gp300 was not secreted in response to hormone stimulation of acini, so it is not a secretory product. Immunoblot analysis showed that gp300 is present in other gastrointestinal tissues and parotid glands. Localization of this nonsecreted sulfated glycoprotein to exocrine secretory granule membranes suggests that gp300 may have a role in granule biogenesis. PMID- 7876333 TI - Cytosolic phospholipase C activity: I. Evidence for coupling with cytosolic guanine nucleotide-binding protein, Gi alpha. AB - In a previous report we showed that glucocorticoid inhibition of cytosolic PLC activity correlated with a reduction in cytosolic Gi alpha levels, suggesting that there may be a functional relationship between cytosolic PLC and cytosolic Gi alpha. In order to establish the nature of the coupling between cytosolic Gi alpha and cytosolic PLC we examined the effects of G-protein activators, and inhibitors on cytosolic PLC activity from rat splenocytes and the rat lymphoma cell line Nb 2, with [3H] PI and [3H]PIP2 as substrates. 1) Neither GTP nor its nonhydrolyzable analogue, GTP gamma S, at 100 microM had any effect on the calcium stimulated as well as the basal PLC activity. 2) However, affinity purified antibodies to Gi alpha 1 and Gi alpha 2 inhibited soluble PLC activity, by 85% and 55%, respectively, with PI as substrate; with PIP2 as substrate, soluble PLC activity was inhibited 50-70% by antibodies to Gi1, whereas antibodies to Gi2 had little effect. 3) Administration of Gi alpha 1 antisense oligonucleotides to splenocytes for 48 h produced 25-40% decrease in cytosolic Gi alpha 1 levels compared to control. The soluble PLC activity with both PI and PIP2 as substrates was also reduced by 25-50% compared to control conditions. This suggest that cytosolic Gi alpha is associated with the activation of splenocyte soluble PLC. 4) Pertussis toxin administered in vivo significantly reduced cytosolic Gi alpha immunoreactivity and soluble PLC activity when PI was used as substrate, providing additional evidence that cytosolic Gi alpha is associated with the activation of soluble PLC. 5) Another agent that has been used extensively to define G-protein coupled processes is NaF/AlCl3. NaF (5 mM; with or without AlCl3) inhibited soluble PLC activity with PIP2 as substrate, in contrast to the stimulatory effect that has been reported in the activation of membrane PLC. 6) Because NaF can act as a protein phosphatase inhibitor, we also tested the effects of trifluoperizine (50 microM, TFP), an inhibitor of protein phosphatase 2B; TFP (50 microM) significantly inhibited soluble PLC activity when PI was used as substrate. These results suggest a direct involvement of cytosolic Gi alpha in the activation of soluble PLC from splenocytes. Other questions pertaining to the functional significance, the nature, and possible substrate preference of the splenocyte Gi alpha coupled PLC is addressed in the second paper. PMID- 7876334 TI - Cytosolic phospholipase C activity: II. Relationship to concanavalin A-induced phosphatidylinositol-turnover in splenocytes. AB - We have described in the first paper the coupling between cytosolic Gi alpha and cytosolic PLC activity in a cell free preparation. In order to establish the functional significance of the cytosolic Gi alpha coupled soluble PLC, we examined the effects of DEX, NaF, and trifluoperizine (TFP) on concanavalin A (Con A)-induced PI-turnover in intact splenocytes and, in parallel, on soluble PLC activity in cytosol preparations. Cytosolic PLC activity was measured with [3H]PI and [3H]PIP2 as substrates. 1) The Con A-induced increase (2-4 fold) in PI turnover in intact splenocytes was paralleled by an 1.2-5-fold increase in soluble PLC activity in vitro. Con A administration also increased cytosolic Gi alpha immunoreactivity 3-6-fold as expected if cytosolic Gi alpha was coupled to soluble PLC activation. 2) DEX (10(-7) M), administered 6 h prior to Con A administration, inhibited the Con A-induced increase in PI-turnover in intact splenocytes. This was paralleled by DEX inhibition of the Con A-induced increase in soluble PLC activity measured in vitro and cytosolic Gi alpha immunoreactivity. 3) We have demonstrated in the first paper that NaF and TFP inhibited soluble PLC activity. Here we show that NaF and TFP inhibited the Con A induced increase in PI-turnover extending the similarities between soluble PLC activity and Con A-stimulated PLC activity in intact splenocytes. 4) In order to examine whether or not the Con A-induced PLC was similar to PLC gamma, we measured PI-turnover induced by Con A or NaVO3 in combination with DEX and PMA. Whereas the Con A-induced PI-turnover was significantly inhibited (40-60%) by DEX, the NaVO3-induced PI-turnover was not affected by DEX. The Con A-induced PI turnover was not affected by PMA (50 nM), but the NaVO3-induced PI-turnover was increased over 2-fold by PMA (50 nM), suggesting that the Con A-induced PLC in intact splenocytes is different from NaVO3-induced PLC. Based on these results a model for the sequential activation of substrate-specific PLCs in splenocyte by mitogen is presented. PMID- 7876335 TI - Inhibition of G1 phase cyclin dependent kinases by transforming growth factor beta 1. AB - Transforming growth factor beta 1 (TGF beta 1) inhibits epithelial cell proliferation late in the G1 phase of the cell cycle. We examined the effect of TGF beta 1 on known late G1 cell cycle regulators in an attempt to determine the molecular mechanism of growth inhibition by this physiological inhibitor. The results demonstrate that TGF beta 1 inhibits the late G1 and S phase specific histone H1 kinase activity of p33cdk2. This inhibition is not due to TGF beta 1's effect on p33cdk2 synthesis, but rather due to its negative effects on the late G1 phosphorylation of p33cdk2. It is also shown that TGF beta inhibits both late G1 cyclin A and cyclin E associated histone H1 kinase activities. The inhibitor has no effects on the synthesis of cyclin E but is shown to inhibit the synthesis of cyclin A protein in a cell cycle dependent manner. If TGF beta 1 is added to cells which have progressed further than 8 hours into G1, then it is without inhibitory effect on cyclin A synthesis. These effects of TGF beta 1 on late G1 cell cycle regulators correlate well with its inhibitory effects on cellular growth and suggest that these G1 cyclin dependent kinases might serve as targets for TGF beta 1-mediated growth arrest. PMID- 7876336 TI - Molecular mechanisms of cellular determination: their relation to chromatin structure and parental imprinting. PMID- 7876337 TI - GPI membrane anchor is determinant in intracellular accumulation of apical plasma membrane proteins in the non-polarized human colon cancer cell line HT-29 18. AB - We have compared the intracellular localization of plasma membrane proteins anchored either with a transmembrane segment or with a glycosylphosphatidylinositol moiety to estimate the effects of membrane anchor on protein segregation in the non-polarized form of the human colon cancer cell line HT-29 18. We have monitored two endogenous proteins: the carcinoembryonic antigen, a glycosylphosphatidylinositol protein and the transmembrane protein dipeptidyl peptidase IV, and two transfected proteins: the glycosylphosphatidylinositol protein Thy-1 and an engineered transmembrane form of Thy-1. Using immunocytochemistry on ultra-thin cryosections and confocal microscopy, we detected a carcinoembryonic antigen-rich vesicular compartment, excluding classical pre-lysosomal and lysosomal markers such as mannose 6 phosphate receptor, lamp-1 and cathepsin D. This compartment, where carcinoembryonic antigen accumulated, excluded the transmembrane protein dipeptidyl peptidase IV and was reduced during the polarization of the cells. Moreover, the glycosylphosphatidylinositol form of Thy-1 also accumulated in the carcinoembryonic antigen-rich compartment whereas the transmembrane form of Thy-1 was excluded. We proposed that, in the non-polarized HT-29 18 cells, accumulation of glycosylphosphatidylinositol proteins independently of transmembrane proteins reveals different intracellular fates for proteins according to their anchor in the plasma membrane. PMID- 7876338 TI - Programmed cell death in Dictyostelium. AB - Programmed cell death (PCD) of Dictyostelium discoideum cells was triggered precisely and studied quantitatively in an in vitro system involving differentiation without morphogenesis. In temporal succession after the triggering of differentiation, PCD included first an irreversible step leading to the inability to regrow at 8 hours. At 12 hours, massive vacuolisation was best evidenced by confocal microscopy, and prominent cytoplasmic condensation and focal chromatin condensation could be observed by electron microscopy. Membrane permeabilization occurred only very late (at 40-60 hours) as judged by propidium iodide staining. No early DNA fragmentation could be detected by standard or pulsed field gel electrophoresis. These traits exhibit some similarity to those of previously described non-apoptotic and apoptotic PCD, suggesting the hypothesis of a single core molecular mechanism of PCD emerging in evolution before the postulated multiple emergences of multicellularity. A single core mechanism would underly phenotypic variations of PCD resulting in various cells from differences in enzymatic equipment and mechanical constraints. A prediction is that some of the molecules involved in the core PCD mechanism of even phylogenetically very distant organisms, e.g. Dictyostelium and vertebrates, should be related. PMID- 7876339 TI - Retention and retrieval: both mechanisms cooperate to maintain calreticulin in the endoplasmic reticulum. AB - Many soluble resident proteins of the endoplasmic reticulum share a COOH-terminal Lys-Asp-Glu-Leu (KDEL) sequence. Current opinion favours a model in which these proteins can escape from the endoplasmic reticulum (ER) by bulk flow and are recognized and sorted in the Golgi apparatus by binding to a specific KDEL receptor, which returns them to the ER. Through biochemical, morphological and mutational analysis we have studied the mechanisms that determine the localization of calreticulin, a soluble 60 kDa KDEL-protein of the ER. Immunogold labelling established the ER localization of calreticulin in transfected and nontransfected COS cells. Although the ER cisternae in transfected cells were enormously dilated and heavily labelled by gold particles we found no significant label in any other compartment. In vivo pulse chase experiments with [35S]methionine followed by biochemical fractionation of calreticulin overexpressing COS cells (50- to 100-fold) revealed that only a minor part of labelled calreticulin leaves the ER. Retrieval from the Golgi was confirmed by a partial redistribution of the endogenous KDEL-receptor as shown by double immunofluorescence. These data suggest a KDEL-independent retention of calreticulin in the ER. Further supporting evidence has come from morphological in vivo studies using calreticulin-transfected and vesicular stomatitis virus (ts045)-infected COS cells. Stimulation of vesicular transport from the ER by releasing the temperature-dependent transport block for the viral G-protein resulted in a small but significant appearance of calreticulin in a post-ER compartment. In contrast a calreticulin mutant, which lacked the Ca(2+)-binding domain but included the KDEL sequence, could escape from the ER to a much higher extent. Secretion of the nonmutated calreticulin was very low (1-2% of total calreticulin in 3 hours) compared to the mutated form (18% in 3 hours). Deletion of the KDEL sequence led to an increase in secretion to 29% over a 3 hour period, which is much less than expected for a secretory protein. Taken together these results strongly support the hypothesis of two independently operating retention/retrieval mechanisms for calreticulin: one providing for direct retention in the ER with a very high capacity and having Ca(2+)-dependent properties; the other a KDEL-based retrieval system for escaped calreticulin present in the Golgi apparatus. PMID- 7876340 TI - CaBP1, a calcium binding protein of the thioredoxin family, is a resident KDEL protein of the ER and not of the intermediate compartment. AB - A cDNA encoding rat CaBP1 has been isolated and sequenced. The deduced polypeptide chain consists of 440 amino acids including two internal thioredoxin like domains and a C-terminal KDEL retention/retrieval signal. Regarding the high degree of identity to the hamster protein P5, CaBP1 is considered to be the homologous rat protein. Previous work has suggested that CaBP1 is a resident luminal protein of the intermediate compartment (Schweizer, A., Peter, F., Nguyen Van, P., Soling, H.D. and Hauri, H.P. (1993) Eur. J. Cell Biol. 60, 366-370). Our conclusion that CaBP1 is a resident protein of the endoplasmic reticulum and not of the intermediate compartment is based on three different approaches: subcellular fractionation, indirect immunofluorescence and overexpression of CaBP1. Subcellular fractionation of Vero cells in a velocity controlled step gradient led to copurification of CaBP1-containing vesicles and several marker proteins for the ER including calreticulin and alpha-SSRP. The intermediate compartment, as defined by a monoclonal antibody against the marker protein p53 (ERGIC-53), could be separated from these ER markers. Double immunofluorescence analysed by laser scanning microscopy showed no significant colocalization between CaBP1 and p53, but between CaBP1 and calreticulin. In addition experiments, Vero cells were infected with VSV tsO45. At 15 degrees C the VSV-G protein accumulated in punctuate structures representing the intermediate compartment, while CaBP1 maintained its original reticular localization. Even after high-level overexpression in COS cells, CaBP1 was not detected in the intermediate compartment, but was efficiently retained in the ER as judged by light microscopy. PMID- 7876341 TI - Expression of N-terminally truncated cyclin B in the Drosophila larval brain leads to mitotic delay at late anaphase. AB - We have introduced an N-terminally truncated form of cyclin B into the Drosophila germ-line downstream of the yeast upstream activator that responds to GAL4. When such lines of flies are crossed to lines in which GAL4 is expressed in imaginal discs and larval brain, the majority of the resulting progeny die at the late pupal stage of development. Very rarely (< 0.1% of progeny) adults emerge that have a mutant phenotype typical of flies with mutations in genes required for the cell cycle; they have rough eyes, deformed wings, abnormal bristles, and die within hours of emergence. The brains of third instar larval progeny show an abnormally high proportion of mitotic cells containing overcondensed chromatids that have undergone anaphase separation, together with cells that cannot be assigned to a particular mitotic stage. Immunostaining indicates that these anaphase cells contain moderate levels of cyclin B, suggesting that persistent p34cdc2 kinase activity can prevent progression from anaphase into telophase. PMID- 7876342 TI - Role of integrins in melanocyte attachment and dendricity. AB - Integrins are a family of proteins known to mediate attachment of cells to extracellular matrix materials. The substratum specificity and cation dependence of specific integrin heterodimers have been extensively characterized, and to a lesser degree specialized roles in cell attachment versus dendricity have been defined in some cell types. In the past decade, melanocyte attachment rate and morphology have been found to have strong substratum dependence, suggesting a major role for integrins in these processes. In order to investigate this aspect of pigment cell biology, human newborn melanocytes were subjected to flow cytometry analysis and plated on a variety of substrata under conditions known to promote or block the binding of specific integrin pairs. Melanocyte attachment to laminin and type IV collagen was promoted by Mg2+ and Mn2+ but not by Ca2+, in the range of concentrations examined. However, dendrite outgrowth from melanocytes already attached on laminin or type IV collagen was promoted by Ca2+ to a far greater degree than by Mg2+, and Mn2+ had no effect on dendrite outgrowth. Flow cytometry analysis revealed that melanocytes expressed beta 1, alpha 2, alpha 3, alpha 5, alpha 6 and alpha v integrin subunits as well as the alpha v beta 3 heterodimer. The influence of substratum on the profile of integrin expression was minimal, but alpha 6 and beta 1 integrins were observed by confocal microscopy to be expressed over the entire cell surface, while alpha 2, alpha 5 and alpha v beta 3 integrins localized along dendritic processes or at their tips. In accordance with the implications of these distribution patterns, anti-beta 1 and anti-alpha 6 integrin monoclonal antibodies blocked melanocyte attachment to laminin, while anti-alpha 2, anti-alpha 5 and anti-alpha v beta 3 inhibited dendrite outgrowth but did not block substratum attachment on either laminin or type IV collagen. On the basis of these data and the known characteristics of integrin molecules, we conclude that melanocyte attachment to laminin is mediated primarily by alpha 6 beta 1 integrin in a Ca(2+)-independent, Mg(2+)- and/or Mn(2+)-dependent manner, while dendrite outgrowth on laminin and type IV collagen requires extracellular Ca2+ and is mediated by alpha v beta 3 as well as alpha 2 and alpha 5 integrins. PMID- 7876343 TI - Synaptonemal complex proteins: occurrence, epitope mapping and chromosome disjunction. AB - We have used polyclonal antibodies against fusion proteins produced from cDNA fragments of a meiotic chromosome core protein, Cor1, and a protein present only in the synapsed portions of the cores, Syn1, to detect the occurrence and the locations of these proteins in rodent meiotic prophase chromosomes. The 234 amino acid Cor1 protein is present in early unpaired cores, in the lateral domains of the synaptonemal complex and in the chromosome cores when they separate at diplotene. A novel observation showed the presence of Cor1 axial to the metaphase I chromosomes and substantial amounts of Cor1 in association with pairs of sister centromeres. The centromere-associated Cor1 protein becomes dissociated from the centromeres at anaphase II and it is not found in mitotic metaphase centromeres. The extended presence of Cor1 suggests that it may have a role in chromosome disjunction by fastening chiasmata at metaphase I and by joining sister kinetochores, which ensures co-segregation at anaphase I. Two-colour immunofluorescence of Cor1 and Syn1 demonstrates that synapsis between homologous cores is initiated at few sites but advances rapidly relative to the establishment of new initiation sites. If the rapid advance of synapsis deters additional initiation sites between pairs of homologues, it may provide a mechanism for positive recombination interference. Immunogold epitope mapping of antibodies to four Syn1 fusion proteins places the amino terminus of Syn1 towards the centre of the synaptonemal complex while the carboxyl terminus extends well into the lateral domain of the synaptonemal complex. The Syn1 fusion proteins have a non-specific DNA binding capacity. Immunogold labelling of Cor1 antigens indicates that the lateral domain of the synaptonemal complex is about twice as wide as the apparent width of lateral elements when stained with electron-dense metal ions. Electron microscopy of shadow-cast surface-spread SCs confirms the greater width of the lateral domain. The implication of these dimensions is that the proteins that comprise the synaptic domain overlap with the protein constituents of the lateral domains of the synaptonemal complex more than was apparent from earlier observations. This arrangement suggests that direct interactions might be expected between some of the synaptonemal complex proteins. PMID- 7876344 TI - The role of duplication of tumour-derived chromosome 15 carrying the rearranged pvt-1 gene in the transformed phenotype of YACUT T-cell lymphoma x G4 T-cell line somatic cell hybrids in dictating the terminal differentiation program of the parental G4 cell. AB - Fusion of the YACUT T-cell lymphoma with the Mls-1a-antigen-specific non tumorigenic T-cell line G4 was previously reported to produce growth-arrested hybrids that could be induced to proliferate in the presence of Mls-1a antigen. The proliferation-suppressed hybrid lines exhibited phenotypic changes as follows: the usually high levels in YACUT of J11d antigen, IL-2 receptor, and c myb expression, which are markers of immature T cells, were all down-regulated; the G4 T-cell function, i.e., contact helper activity for B-cell proliferation in T/B cell collaboration, was retained. Furthermore, fusion of the YACUT lymphoma with a killer T-cell line produced growth-arrested and tetraploid somatic cell hybrids having killer activity. Thus, in addition to the transformed phenotype (autonomous proliferation in vitro), the antigen-specific non-tumorigenic T-cell line genomes introduced into the YACUT lymphoma suppressed the immature phenotypes of YACUT and imposed their own programming of terminally differentiated traits on the hybrids. Prolonged growth of the proliferation suppressed hybrid lines by repeated antigenic stimulation was previously reported to result in the appearance of transformed hybrids, which was accompanied by both a reversion of c-myc expression to the levels of YACUT and an increase in the number of chromosome 15. The present study revealed that the amplification of chromosome 15 resulted from the duplication of the tumour-derived chromosome 15 carrying the rearranged pvt-1 gene. However, the differentiated phenotypes of the hybrids remained mostly unchanged upon cell transformation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876345 TI - Ultrastructure of the proteoliaisin-ovoperoxidase complex and its spatial organization within the Strongylocentrotus purpuratus fertilization envelope. AB - Ovoperoxidase is a cortical granule-derived enzyme that hardens the sea urchin fertilization envelope by catalyzing the formation of dityrosine residues. Ovoperoxidase works in concert with a second protein, proteoliaisin, which anchors ovoperoxidase to the nascent fertilization envelope in a divalent cation dependent manner. In this study, we examined the Ca(2+)-dependent interaction of proteoliaisin with ovoperoxidase in rotary-shadowed Pt replicas. Ovoperoxidase, a uniformly sized globular molecule, binds to a distal portion of rod-shaped proteoliaisin when low concentrations of Ca2+ are present. Higher Ca2+ concentrations lead to the formation of extended proteoliaisin strands that are decorated along their lengths with ovoperoxidase. Using immunogold labeling, we also examined the assimilation of these two proteins into the fertilization envelope in quick-frozen, deeply etched samples. Both proteins are abundant in the fertilization envelope as early as one minute after fertilization. Coincident with paracrystalline coating of the envelope, the labeling density is markedly reduced, suggesting that antigenic sites may be masked by the paracrystalline coat. This suggests that the ovoperoxidase-proteoliaisin complex resides within the central portion of the fertilization envelope, rather than in the paracrystalline coat. PMID- 7876346 TI - The fission yeast cdc19+ gene encodes a member of the MCM family of replication proteins. AB - We have cloned and characterized the fission yeast cdc19+ gene. We demonstrate that it encodes a structural homologue of the budding yeast MCM2 protein. In fission yeast, the cdc19+ gene is constitutively expressed, and essential for viability. Deletion delays progression through S phase, and cells arrest in the first cycle with an apparent 2C DNA content, with their checkpoint control intact. The temperature-sensitive cdc19-P1 mutation is synthetically lethal with cdc21-M68. In addition, we show by classical and molecular genetics that cdc19+ is allelic to the nda1+ locus. We conclude that cdc19p plays a potentially conserved role in S phase. PMID- 7876347 TI - Cell cycle regulation of the p34cdc2/p33cdk2-activating kinase p40MO15. AB - A key component of Cdc2/Cdk2-activating kinase (CAK) is p40MO15, a protein kinase subunit that phosphorylates the T161/T160 residues of p34cdc2/p33cdk2. The level and activity of p40MO15 were essentially constant during cleavage of fertilised Xenopus eggs and in growing mouse 3T3 cells, but serum starvation of these cells reduced both the level and activity of p40MO15. Although the level and activity of endogenous p40MO15 did not vary in the cell cycle, we found that bacterially expressed p40MO15 was activated more rapidly by M-phase cell extracts than by interphase cell extracts. Bacterially expressed p40MO15 was phosphorylated mainly on serine 170 (a p34cdc2 phosphorylation site) by mitotic cell extracts, but mutation of S170 to alanine did not affect the activation of p40MO15, whereas mutation of T176 (the equivalent site to T161/T160 in p34cdc2/p33cdk2) abolished the activation of P40MO15. These studies suggest that the level and activity of p40MO15 is probably not a major determinant of p34cdc2/p33cdk2 activity in the cell cycle, and that the activation of p40MO15 may require phosphorylation on T176. PMID- 7876348 TI - A Rab4-like GTPase in Dictyostelium discoideum colocalizes with V-H(+)-ATPases in reticular membranes of the contractile vacuole complex and in lysosomes. AB - In the course of screening a cDNA library for ras-related Dictyostelium discoideum genes, we cloned a 0.7 kb cDNA (rabD) encoding a putative protein that was 70% identical at the amino acid level to human Rab4. Rab4 is a small M(r) GTPase, which belongs to the Ras superfamily and functions to regulate endocytosis in mammalian cells. Southern blot analysis indicated that the rabD cDNA was encoded by a single copy gene while Northern blot analysis revealed that the rabD gene was expressed at relatively constant levels during growth and differentiation. Affinity-purified antibodies were prepared against a RabD fusion protein expressed in bacteria; the antibodies recognized a single 23 kDa polypeptide on western blots of cell extracts. Density gradient fractionation revealed that the RabD antigen co-distributed primarily with buoyant membranes rich in vacuolar protons pumps (V-H(+)-ATPases) and, to a lesser extent, with lysosomes. This result was confirmed by examining cell lines expressing an epitope-tagged version of RabD. Magnetically purified early endocytic vesicles and post-lysosomal vacuoles reacted more weakly with anti-RabD antibodies than did lysosomes. Other organelles were negative for RabD. Double-label indirect immunofluorescence microscopy revealed that RabD and the 100 kDa V-H(+)-ATPase subunit colocalized in a fine reticular network throughout the cytoplasm. This network was reminiscent of spongiomes, the tubular elements of the contractile vacuole system. Immunoelectron microscopy confirmed the presence of RabD in lysosome fractions and in the membranes rich in V-H(+)-ATPase. We conclude that a Rab4-like GTPase in D. discoideum is principally associated with the spongiomes of contractile vacuole complex. PMID- 7876349 TI - Differential effects of compartment deacidification on the targeting of membrane and soluble proteins to the vacuole in yeast. AB - Lysosomal/vacuolar protein targeting is dependent on compartment acidification. In yeast, sorting of soluble vacuolar proteins such as carboxypeptidase Y is sensitive to acute changes in vacuolar pH. In contrast, the vacuolar membrane protein alkaline phosphatase is missorted only under conditions of chronic deacidification. We have undertaken a temporal analysis to define further the relationship between compartment acidification and sorting of soluble and membrane vacuolar proteins. Depletion of either the Vma3p or Vma4p subunits of the yeast vacuolar ATPase over time resulted in loss of vacuolar ATPase activity and vacuolar acidification. A kinetic delay in processing of carboxypeptidase Y occurred concomitant with these physiological changes while transport of alkaline phosphatase remained unaffected. Carboxypeptidase S, another vacuolar hydrolase that transits through the secretory pathway as an integral membrane protein, displayed a pH sensitivity similar to that of soluble vacuolar proteins. These results indicate that compartment acidification is tightly coupled to efficient targeting of proteins to the vacuole and that there may be multiple distinct mechanisms for targeting of vacuolar membrane proteins. PMID- 7876350 TI - Recruitment of antigenic gamma-tubulin during mitosis in animal cells: presence of gamma-tubulin in the mitotic spindle. AB - It has been claimed repeatedly that gamma-tubulin is exclusively localized at the spindle poles in mitotic animal cells, where it plays a role in microtubule nucleation. In addition to this localization, we have observed a gamma-tubulin specific staining of the mitotic spindle in several animal cells (human, kangaroo rat, mouse, Chinese hamster, Xenopus and Drosophila) using five polyclonal antibodies raised against unique gamma-tubulin sequences and four different fixation protocols. In HeLa and PtK2 cells, gamma-tubulin was detected in the mitotic spindle from late prometaphase to telophase. In contrast, in other cell types, it was detected in metaphase only. In all cases we failed to detect gamma tubulin in the short aster microtubules at the spindle poles. Electron microscopic observation revealed that at least part of the gamma-tubulin localized on the surface of spindle microtubules with a preferential distribution along kinetochore microtubules. In HeLa cells, the amount of antigenic gamma tubulin was fairly constant in the spindle poles during mitosis from prometaphase to telophase. In contrast, gamma-tubulin appeared in the mitotic spindles in prometaphase. The amount of gamma-tubulin decreased in telophase, where it relocalized in the interzone. In metaphase cells about 15-25% of the total fluorescence was localized at the spindle poles, while 75-85% of the fluorescence was distributed over the rest of the spindle. These results suggest that the localization and timing of gamma-tubulin during the cell cycle is highly regulated and that is physiological role could be more complex and diverse than initially assumed. PMID- 7876351 TI - Purification and characterization of ensconsin, a novel microtubule stabilizing protein. AB - In previous studies (Bulinski and Borisy (1979). Proc. Nat. Acad. Sci. 76, 293 297; Weatherbee et al. (1980). Biochemistry 19, 4116-4123) a microtubule associated protein (MAP) of M(r) approximately 125,000 was identified as a prominent MAP in HeLa cells. We set out to perform a biochemical characterization of this protein, and to determine its in vitro functions and in vivo distribution. We determined that, like the assembly-promoting MAPs, tau, MAP2 and MAP4, the 125 kDa MAP was both proteolytically sensitive and thermostable. An additional property of this MAP; namely, its unusually tight association with a calcium-insensitive population of MTs in the presence of taxol, was exploited in devising an efficient purification strategy. Because of the MAP's tenacious association with a stable population of MTs, and because it appeared to contribute to the stability of this population of MTs in vitro, we have named this protein ensconsin. We examined the binding of purified ensconsin to MTs; ensconsin exhibited binding that saturated its MT binding sites at an approximate molar ratio of 1:6 (ensconsin:tubulin). Unlike other MAPs characterized to date, ensconsin's binding to MTs was insensitive to moderate salt concentrations (< or = 0.6 M). We further characterized ensconsin in immunoblotting experiments using mouse polyclonal anti-ensconsin antibodies and antibodies reactive with previously described MAPs, such as high molecular mass tau isoforms, dynamin, STOP, CLIP-170 and kinesin. These experiments demonstrated that ensconsin is distinct from other proteins of similar M(r) that may be present in association with MTs. Immunofluorescence with anti-ensconsin antibodies demonstrated that ensconsin was detectable in association with most or all of the MTs of several lines of human epithelial, fibroblastic and muscle cells; its in vivo properties and distribution, especially in response to drug or other treatments of cells, were found to be different from those of MAP4, the predominant MAP found in these cell types. We conclude that ensconsin, a MAP found in a variety of human cells, is biochemically - and perhaps functionally - distinct from other MAPs present in non-neuronal cells. PMID- 7876352 TI - TRiC-P5, a novel TCP1-related protein, is localized in the cytoplasm and in the nuclear matrix. AB - We have recently reported the cloning of a novel protein, TRiC-P5, with significant homology with protein 1 of the t-complex (TCP1). In the present study, the cellular localization of TRiC-P5 in Raji cells has been determined using an antiserum raised against a 18.5 kDa fusion protein. Results from cell fractionation and immunoblot studies indicate that TRiC-P5 is mainly localized in the cytoplasm. In addition, a significant part of TRiC-P5 is also found in the nucleus where it is attached to the nuclear matrix, a complex filament network involved in essential cellular functions such as DNA replication, and RNA transcription and maturation. Immunofluorescence experiments using the anti-TRiC P5 antibodies confirm these results. We also provide evidence that, in the cytoplasm, TRiC-P5 is part of a large protein complex, most probably the TCP1 ring complex (TRiC), a hetero-oligomeric ring complex that plays a role of molecular chaperone in the folding of actin and tubulin. PMID- 7876353 TI - Dinoflagellates have a eukaryotic nuclear matrix with lamin-like proteins and topoisomerase II. AB - Unicellular Dinoflagellates represent the only eukaryotic Phylum lacking histones and nucleosomes. To investigate whether Dinoflagellates do have a nuclear matrix that would modulate the supramolecular organization of their non-nucleosomal DNA and chromosomes, cells of the free-living unarmored Dinoflagellate Amphidinium carterae were encapsulated in agarose microbeads and submitted to sequential extraction with non-ionic detergents, nucleases and 2 M NaCl. Our results demonstrate that this species has a residual nuclear matrix similar to that of vertebrates and higher plants. The cytoskeleton-nuclear matrix complex of A. carterae shows a relatively intricate polypeptide pattern. Immunoblots with different antibodies reveal several intermediate filament types of proteins, one of which is immunologically related to vertebrate lamins, confirming that these proteins are ancestral members of the IF family, which is highly conserved in eukaryotes. A topoisomerase II homologue has also been identified in the nuclear matrix, suggesting that these structures could play a role in organizing the Dinoflagellate DNA in loop domains. Taken together our results demonstrate that the nuclear matrix is an early acquisition of the eukaryotic nucleus, independent of histones and nucleosomes in such a way that the mechanisms controlling the two levels of organization in eukaryotic chromatin would be molecularly and evolutionarily independent. PMID- 7876354 TI - Molecular genetic truncation analysis of filament assembly and phosphorylation domains of Dictyostelium myosin heavy chain. AB - Conventional myosin ('myosin II') is a major component of the cytoskeleton in a wide variety of eukaryotic cells, ranging from lower amoebae to mammalian fibroblasts and neutrophils. Gene targeting technologies available in the Dictyostelium discoideum system have provided the first genetic proof that this molecular motor protein is essential for normal cytokinesis, capping of cell surface receptors, normal chemotactic cell locomotion and morphogenetic shape changes during development. Although the roles of myosin in a variety of cell functions are becoming clear, the mechanisms that regulate myosin assembly into functional bipolar filaments within cells are poorly understood. Dictyostelium is currently the only system where mutant forms of myosin can be engineered in vitro, then expressed in their native context in cells that are devoid of the wild-type isoform. We have utilized this technology in combination with nested truncation and deletion analysis to map domains of the myosin tail necessary for in vivo and in vitro filament assembly, and for normal myosin heavy chain (MHC) phosphorylation. This analysis defines a region of 35 amino acids within the tail that is critical for filament formation both for purified myosin molecules and for myosin within the in vivo setting. Phosphorylation analysis of these mutants in intact cytoskeletons demonstrates that the carboxy-terminal tip of the myosin heavy chain is required for complete phosphorylation of the myosin tail. PMID- 7876355 TI - Topoisomerase II expression and VM-26 induction of DNA breaks during spermatogenesis in Xenopus laevis. AB - The relative content of topoisomerase II (topo II) and the induction of topo-II mediated DNA damage and cellular abnormalities have been characterized in developing spermatogenic cells of Xenopus laevis to gain an insight into the role of topo II during spermatogenesis. Decatenation assays identified topo II activity in nuclear extracts from spermatocytes and pre-elongate spermatids, but not in extracts from elongate spermatids or sperm. Extracts from early-mid spermatids contained 14% (per cell) of the decatenation activity found in spermatocyte extracts. Immunoblots of SDS extracts from whole cells and nuclei from both spermatocytes and pre-elongate spermatids, but not elongate spermatids or sperm, resolved a 180 kDa polypeptide that reacts with polyclonal antisera to Xenopus oocyte topo II, an antipeptide antibody (FHD29) to human topo II alpha and beta, and an antipeptide antibody to human topo II alpha, suggesting homology between Xenopus spermatogenic cell topo II and mammalian topo II alpha. Immunofluorescence microscopy of topo II in testis cryosections revealed the presence of topo II in nuclei of all spermatogenic stages, but not in sperm. The relative levels of topo II estimated from fluorescence intensity were highest in spermatogonia and spermatocytes, then early-mid spermatids, followed by elongate spermatids and somatic cells. Incubation of isolated spermatogenic cells with teniposide (VM-26), a topo II-targetted drug, resulted in a dose-dependent induction of DNA breaks in all spermatocytes and spermatid stages to nuclear elongation stages, as analyzed by alkaline single cell gel electrophoresis. Addition of 0.5-50 microM VM-26 to spermatogenic cell cultures for 27 hours resulted in stage-dependent abnormalities. Mid-late spermatid stages were relatively resistant to VM-26-induced damage. In contrast, meiotic division stages were arrested and spermatogonia B were killed by VM-26, and VM-26 induced abnormal chromosome condensation in pachytene spermatocytes. The results of these studies show that cellular levels of topo II are stage-dependent during spermatogenesis, that most spermatogenic stages are sensitive to topo II-mediated DNA damage, and that spermatogonia B, meiotic divisions and pachytene spermatocytes are particularly sensitive to induction of morphological abnormalities and cell death during acute exposure to topo II-targetted drugs. PMID- 7876356 TI - cAMP does not regulate [Ca2+]i in human tracheal epithelial cells in primary culture. AB - Human tracheal epithelial cells in primary culture respond to different receptor agonists with different peak intracellular calcium concentrations. From resting concentration 138 +/- 13 nM, bradykinin (0.1 microM) produces an increase to a maximum of 835 +/- 195 nM, histamine (10 microM) to 352 +/- 51 nM, and ATP (5-500 microM) to more than 1500 nM. Nine of 14 cultures also responded to isoproterenol (10 microM), though with a smaller increase, to 210 +/- 29 nM. A response was observed with isoproterenol, and epinephrine, but not norepinephrine, phenylephrine or methoxamine, was inhibited by propranolol but not phentolamine, and so this appeared to be a beta-adrenergic response. However, no response could be detected to adenosine, prostaglandin E2 or forskolin, agents that activate adenylate cyclase, or to permeant analogs of cAMP (CPT-cAMP or db-cAMP). The intracellular calcium response to isoproterenol did not follow either the time course or the desensitization pattern of the cAMP response. Thus, this response to isoproterenol is not mediated by cAMP. No relation was demonstrated between cAMP production by other agonists and the response of intracellular calcium. Pretreatment with agents that increase cAMP did not affect the calcium responses to ATP or bradykinin. Thus, cAMP does not regulate intracellular calcium concentration in human tracheal epithelial cells. The variation in peak intracellular calcium responses to various agonists may be explained by the presence of multiple second messengers (other than cAMP), multiple intracellular pools of calcium, or cell heterogeneity. The agonists tested had the same relative potency in cells from patients with cystic fibrosis as in non-cystic fibrosis cells. PMID- 7876357 TI - The effects of the neuN and neuT genes on differentiation and transformation of mammary epithelial cells. AB - Overexpression of the proto-oncogene product, p185neuN, in a non-tumorigenic mammary epithelial line (31E) facilitates aspects of lactogenic differentiation. Formation of branching cords and induction of beta-casein synthesis by 31E cells normally require co-culture of these cells with fibroblasts, or the presence of collagen or fibronectin. In contrast, 31E cells expressing p185neuN spontaneously form branching cords when grown on tissue culture plastic and can synthesize beta casein in the absence of exogenous substrates or feeder layers. Under these conditions, the cells deposit laminin and fibronectin, indicating a possible role for p185neuN in the deposition of extracellular matrix proteins. Overexpression of the corresponding oncogene product, p185neuT, has markedly different effects. Expression of p185neuT does not facilitate the formation of branching cords or the synthesis of beta-casein when grown on tissue culture plastic, although these cells do deposit laminin and fibronectin. Confocal microscopy indicates a significant difference in the distribution of laminin and fibronectin in 31E cells expressing p185neuT compared to those expressing p185neuN. The effects of p185neuN and p185neuT expression on cell transformation depend on cell type. Expression of both p185neuN and p185neuT increases anchorage-independent growth of 31E cells, but only p185neuT induces anchorage-independent growth of NIH 3T3 fibroblasts. This lineage specificity in the action of p185neuN may be related to observations that overexpression of p185c-erbB-2 (the human homologue of p185neuN) is only associated with the development of human epithelial cancers. The effects of p185neuN on laminin deposition by 31E cells may be relevant to the transforming ability of p185neuN, since laminin can induce anchorage-independent growth of mouse mammary cells. These results suggest that p185neuN and p185neuT could exert their effects on differentiation and transformation of mammary epithelial cells in part by promoting the deposition of extracellular matrix proteins. PMID- 7876358 TI - Ectoenzyme regulation by phenotypically distinct fibroblast sub-populations isolated from the human mammary gland. AB - Inter- and intralobular mammary fibroblasts have been separated from normal human breast tissue and cultured to study the differential expression of ectoenzymes present within the stroma of the normal gland and associated with breast cancers. Specific ectoenzymes were identified by indirect immunofluorescence and quantified by flow cytometry and semi-quantitative PCR. A consistent difference was noted between the two fibroblast sub-populations at early passage in respect of dipeptidyl peptidase IV (DPP IV) and aminopeptidase N (APN) expression. Early passage intralobular fibroblasts were positive for APN but negative for DPP IV, as seen in the intact tissue. However, with continued sub-culture they gradually began to express DPP IV, until at later passages they became indistinguishable from the interlobular fibroblasts, which were APN and DPP IV-positive at all stages in culture, as they are in intact tissue. Neutral endopeptidase (NEP/CALLA/CD10) is not expressed by normal adult breast fibroblasts but is found in the stroma associated with over 60% of breast cancers. It was up-regulated in vitro on both inter- and intralobular fibroblasts, with final levels that were significantly (< 14 times) higher on the former in all pairs of preparations from individual donors analysed. This difference persisted with continued passage, and levels of the ectoenzyme and its messenger RNA were further up-regulated by hydrocortisone in both populations. These results demonstrate that phenotypically distinct cultures of human mammary fibroblast sub-populations can be used to study the regulation of these stromal ectoenzymes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876359 TI - Supramolecular assemblies of the Ascaris suum major sperm protein (MSP) associated with amoeboid cell motility. AB - Sperm of the nematode, Ascaris suum, are amoeboid cells that do not require actin or myosin to crawl over solid substrata. In these cells, the role usually played by actin has been taken over by major sperm protein (MSP), which assembles into filaments that pack the sperm pseudopod. These MSP filaments are organized into multi-filament arrays called fiber complexes that flow centripetally from the leading edge of the pseudopod to the cell body in a pattern that is intimately associated with motility. We have characterized structurally a hierarchy of helical assemblies formed by MSP. The basic unit of the MSP cytoskeleton is a filament formed by two subfilaments coiled around one another along right-handed helical tracks. In vitro, higher-order assemblies (macrofibers) are formed by MSP filaments that coil around one another in a left-handed helical sense. The multi filament assemblies formed by MSP in vitro are strikingly similar to the fiber complexes that characterize the sperm cytoskeleton. Thus, self-association is an intrinsic property of MSP filaments that distinguishes these fibers from actin filaments. The results obtained with MSP help clarify the roles of different aspects of the actin cytoskeleton in the generation of locomotion and, in particular, emphasize the contributions made by vectorial assembly and filament bundling. PMID- 7876360 TI - Exploitation of microfilament proteins by Listeria monocytogenes: microvillus like composition of the comet tails and vectorial spreading in polarized epithelial sheets. AB - Effective cell-to-cell spreading of the facultative intracellular pathogen Listeria monocytogenes requires the interaction between bacteria and the microfilament system of the host cell. By recruiting actin filaments into a 'comet tail' localized at one pole of the bacterial cell wall, Listeria become mobile and propel themselves through the cytoplasm. They create protrusions at the plasma membrane that can invaginate adjacent cells. In this work, we have analysed the structural composition of Listeria-recruited microfilaments in various epithelial cell lines by immunofluorescence microscopy. The microfilament crosslinking proteins alpha-actinin, fimbrin and villin were localized around bacteria as soon as actin filaments could be detected on the bacterial surface. Surprisingly, the same was found for ezrin/radixin, proteins involved in linking microfilaments to the plasma membrane. We found that in a polarized cell line derived from brush border kidney epithelium (LLC-PK1), the actin filaments surrounding intracytoplasmic motile bacteria show the same immunoreactivity as the brush border-like microvilli, when analysed by a specific actin antibody. The successful invasion of polarized LLC-PK1 islets is vectorial, i.e. it progresses predominantly from the periphery of the islets towards the centre. Infection of the peripheral cells is sufficient for infiltration of the entire cellular islets, without any further contact with the extracellular milieu. This is in contrast to nonpolarized epithelial sheets, which can be invaded from the apical surface of any individual cell. The importance of active bacterial motility in this vectorial spreading is emphasized by our finding that an isogenic Listeria mutant that is unable to recruit actin filaments cannot colonize polarized epithelial layers but accumulates in the peripheral cells of the islets. PMID- 7876362 TI - Medicine as an agency of social control: Part two. PMID- 7876361 TI - Tropomyosin isoforms in rat neurons: the different developmental profiles and distributions of TM-4 and TMBr-3 are consistent with different functions. AB - Antipeptide antisera specific for TM-4 and TMBr-3, the two tropomyosin isoforms in neurons, were used to investigate the concentrations and distributions of these F-actin-binding proteins in neurons in vitro and in vivo. TM-4 and TMBr-3 tropomyosins had different developmental profiles. TM-4 was found mainly in immature stages, while the concentration of TMBr-3 increased with maturation. The two isoforms also had different subcellular distributions. TM-4 was concentrated in the growth cones of cultured neurons and, in vivo, in areas where neurites were growing. Later, when development was complete, TM-4 was restricted to postsynaptic sites in the cerebellar cortex, whereas TMBr-3 was found in the presynaptic terminals. These data suggest that the tropomyosin isoforms have different functions, through their interaction with the actin cytoskeleton. TM-4 may be involved in the motile events of neurite growth and synaptic plasticity, while TMBr-3 could play a role in stabilizing neuronal networks and synaptic functioning. PMID- 7876363 TI - Effect of famotidine on ciprofloxacin pharmacokinetics after single intravenous and oral doses in rats. AB - The effect of intravenous (3.5 mg/kg) and oral (5 mg/kg) famotidine on ciprofloxacin pharmacokinetics after single (i.v.) intravenous (5 mg/kg) and oral (20 mg/kg) doses were examined in the rat. Famotidine co-administration significantly increased the terminal elimination half-life of ciprofloxacin (54% and 29% following i.v. and oral administration, respectively) and tended to reduce the total body clearance by 27% and 34% following i.v. and oral routes, respectively. The area under the plasma concentration-time curve and the mean residence time in the body after i.v. and oral doses were significantly increased following famotidine co-administration. No changes in the steady-state apparent volume of distribution was observed after i.v. administration. The maximum plasma concentration and the time to peak concentration after oral dosing were also unaffected. These results suggest a possible reduction in the total clearance of ciprofloxacin, owing to inhibition of its renal tubular excretion by famotidine. Further studies are warranted to determine whether this interaction occurs in humans. PMID- 7876364 TI - Drug-related admissions to an Australian hospital. AB - This study was conducted to determine the prevalence of drug-related hospital admissions in southern Tasmania, Australia. The causes of consecutive admissions to medical wards of the Royal Hobart Hospital were reviewed. Comprehensive data were collected over a 10-week period on 691 admissions (median age: 67 years and range: 11-97 years; 50.8% males). Sixty-eight (9.8%) of the admissions were classified as being either probably or definitely drug-related. Most of these admissions were attributable to intentional overdose (38.2%) or an adverse drug reaction (30.9%). The overdoses often involved benzodiazepines or antipsychotics. Gastrointestinal bleeding related to the use of nonsteroidal anti-inflammatory drugs was the most common adverse drug reaction (38.1% of all reactions). Other drug-related admission categories were poor compliance (14.7%), dosage decrease or therapy cessation by a doctor producing an exacerbation of symptoms (7.4%), substance abuse (4.4%) and drug interaction (4.4%). Patients with a drug-related admission were, on average, younger than the other medical admissions, with no significant difference in gender. Patients admitted due to an overdose or substance abuse were younger than other drug-related admissions and non-drug related admissions. In conclusion, this study has determined that almost 10% of medical admissions to the hospital are drug-related and it is estimated that 40 to 50 elderly people are admitted each year suffering from gastrointestinal bleeding related to nonsteroidal anti-inflammatory drugs. PMID- 7876365 TI - Stability of dantrolene oral suspension prepared from capsules. AB - The chemical stability of an extemporaneously compounded dantrolene oral suspension (5 mg/ml dantrolene sodium) in Syrup BP containing citric acid with and without methyl hydroxybenzoate preservative was studied on storage at 5, 25 and 40 degrees C for 150 days in high density polyethylene dispensing bottles. The amount of dantrolene free acid in suspension was monitored by a stability indicating HPLC assay. There was no significant decomposition of dantrolene under all storage conditions irrespective of the presence of preservative. The results show that the formulation of dantrolene oral suspension provides a convenient and stable dosage form for use in pediatric patients and in those unable to swallow capsules. It is recommended that the formulation be stored at room temperature and in the absence of microbiological testing a shelf-life of 30 days is proposed for the product prepared with preserved syrup. PMID- 7876366 TI - The extent of sodium and water administration associated with i.v. drug infusions in a surgical unit. AB - OBJECTIVE: To quantify sodium and water administered to surgical patients but not actually prescribed by the physician. METHODS: Computerized medication records of 1208 surgical patients who were operated on in 1992 were analysed retrospectively. Only prescriptions for intravenous (i.v.) drugs and fluids were selected. RESULTS: Thirteen of 143 i.v. drugs made up 68.3% of prescriptions for i.v. drugs. Patients received a median of three i.v. drugs daily. Patients were on i.v. therapy for a mean of 4.6 +/- 6.0 days (range 1-140, median 3 days). On 24% of patient-days, patients received more than 100 mEq of sodium which was not consciously prescribed, and on 20.4% of patient-days they had an extra daily intake of 750 ml of water or more. One fourth of the total sodium and more than 15% of fluid administered to patients was in the form of NaCl 0.9%, used as a vehicle for i.v. drugs. CONCLUSIONS: There is a considerable amount of sodium and water administered to patients without a specific prescription. The promotion of knowledge about the correct administration of i.v. drugs is an important task for the clinical pharmacist. If this is achieved, it will allow for an optimal administration of drugs as well as the prevention of possible side effects from an intended sodium and water administration. PMID- 7876367 TI - Penile self-injection for impotence in patients after radical cystectomy. PMID- 7876368 TI - Shelf-lives and factors affecting the stability of morphine sulphate and meperidine (pethidine) hydrochloride in plastic syringes for use in patient controlled analgesic devices. AB - Published reports regarding the stability of morphine are at variance, especially in syringes used in patient-controlled analgesia (PCA) devices. In addition to the effects of container type and vehicle, reasons for this variation include the effect of excipients temperature and light during storage. Furthermore, the literature varies regarding the mechanisms of decomposition for morphine. To our knowledge, the stability of meperidine (pethidine) stored in plastic syringes has not been reported. The purposes of this study were to investigate the stability of morphine sulphate (1 and 5 mg/ml) and meperidine hydrochloride (5 and 10 mg/ml) in plastic syringes for use in PCA devices for a duration of 12 weeks, and evaluate the influence of light (240 foot-candles), temperature (-20, 4 and 23 degrees C), diluent (5% dextrose or normal saline), and drug concentration on the stability of these narcotic analgesics. Samples were taken bi-weekly for solutions protected from light and weekly for solutions exposed to light. Morphine sulphate and meperidine hydrochloride concentrations were quantified using independent, stability-indicating, high performance liquid chromatographic assays. The within-day and between-day coefficients of variation for these assays were < or = 4% over each of the concentration ranges studied. Under the conditions of this study, it is proposed that although decomposition of morphine to its main product, pseudomorphine, can be interpreted using first-order kinetics, consecutive (to form the N-oxide) and parallel mechanisms (to form apomorphine) exist. Morphine solutions were more stable in normal saline than in 5% dextrose. Shelf-life data indicate that morphine is stable for at least 6 weeks when protected from light.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876369 TI - Preventing potential drug interactions in community pharmacy. AB - With ongoing debate on health care reform including improved pharmaceutical care, there is much current concern about drug interactions and their prevention. Many patients visit more than one doctor for their different diseases and receive more than one drug at a time, and often doctors are unaware of all the medications their patients are taking and the risks to which their patients are exposed when treated with multiple drugs. Pharmacists in the community setting or hospital are the most accessible health care providers able to intervene when faced with potential drug interactions that may occur during patients' multiple drug therapy. A few selected examples of potential drug-drug interactions and interventions instituted are presented in this paper. Possible mechanisms for the drug interactions are also discussed. It is hoped that more documentation of pharmacists' involvement in such interventions will demonstrate the true value of pharmaceutical care. PMID- 7876370 TI - Omission of aspirin in patients following coronary artery bypass graft surgery. AB - Graft patency is a major factor contributing to the long-term results of coronary artery bypass graft (CABG) surgery. The systematic overview of the Antiplatelet Trialists' Collaboration provides unequivocal evidence that antiplatelet therapy reduces by nearly one-half the odds of coronary graft occlusion following CABG. We retrospectively reviewed patients undergoing CABG during 1993 at the Cardiothoracic Unit, Northern General Hospital, to determine the incidence of, and indications for, aspirin omission following CABG: 462 patients with isolated CABG, 75 patients with a combined CABG and a heart valve procedure and 21 patients with a combined CABG and other non-valve procedure. Thirty-six patients (7.5%) with isolated CABG and CABG combined with a non-valve procedure were not prescribed aspirin. The reasons for aspirin omission were categorized into three groups depending on whether omission was fully justified (group 1), possibly justified (group 2) or unjustified (group 3). Twenty-one patients were in groups 2 and 3, nine of whom were started on aspirin 2-6 weeks after discharge without any ill effect. Forty-two patients were discharged from hospital on a three month course of warfarin. Four months later four patients had died, 24 had changed to aspirin, 10 were still on warfarin and four were on neither drug. Aspirin was sometimes omitted without clear indications. Better provisions for supervision should be made by either the General Practitioner or Hospital Practitioner during the change-over period from oral anticoagulation to antiplatelet therapy in patients on a short course of warfarin. PMID- 7876372 TI - Stability of caffeine oral formulations for neonatal use. AB - The stability of an oral formulation of 10 mg/ml caffeine citrate (equivalent to 5.03 mg/ml caffeine free base), which was preserved with potassium sorbate, was assessed at a range of temperatures. There was no appreciable change in pH or caffeine content over 1 year, even at storage temperatures of 32 degrees C and 45 degrees C. A batch-to-batch difference in the stability of potassium sorbate was detected, with losses over 1 year of 2% and 11% for two batches at 25 degrees C and 10% and 30%, respectively, at 45 degrees C. The formulation complied with the Antimicrobial Preservative Efficacy test of the British Pharmacopoeia throughout a period of storage at 25 degrees C for 1 year. There was no detectable benefit to preservative efficacy by adding 20% w/v sorbitol as an osmotic agent. The formula with no sorbitol may be preferable due to the potential for sorbitol to cause gastrointestinal upset. A shelf-life of 1 year at room temperature is feasible. The additional precaution of limiting the in-use storage life to 1 month after opening is recommended to ensure acceptable microbiological quality. PMID- 7876371 TI - Dual bezafibrate-simvastatin therapy for combined hyperlipidaemia. AB - Statins and fibrates are both effective in the treatment of hyperlipidaemias but are not recommended in combination because episodes of rhabdomyolysis have followed combined lovastatin-gemfibrozil therapy. We assessed treatment with dual bezafibrate-simvastatin therapy in routine clinical practice. In 22 patients, total cholesterol, LDL-cholesterol and triglycerides fell by 20.1% (P < 0.0001), 35.1% (P < 0.001) and 31% (P < 0.05) respectively, and HDL-cholesterol rose by 18.4% (P < 0.05) on combination therapy. The reduction in cholesterol followed the introduction of simvastatin, while the decrease in triglycerides followed treatment with bezafibrate. No patient developed myopathy. We conclude that dual simvastatin-bezafibrate therapy is well tolerated and may reduce triglyceride concentrations, but offers no advantage in cholesterol reduction over treatment with simvastatin alone. PMID- 7876373 TI - Stability of piperacillin sodium in the presence of tazobactam sodium in 5% dextrose and normal saline injections. AB - The stability of piperacillin sodium in the presence of tazobactam sodium in 5% dextrose and normal saline i.v. admixtures has been determined using a modified stability-indicating high performance liquid chromatography assay method reported in the literature. The solutions were stored at room and refrigerator temperatures in plastic bags. They remained clear throughout the study although the pH values decreased slightly during storage. The solutions were stable for 2 days at 25 degrees C and for 28 days at 5 degrees C. Tazobactam sodium appears to have a slight adverse effect on the stability of piperacillin sodium. PMID- 7876374 TI - Separation and characterization of 25-hydroxyvitamin D3 3-sulfate in human plasma by high-performance liquid chromatography. AB - The separation and characterization of 25-hydroxyvitamin D3 3-sulfate in human plasma are carried out by high-performance liquid chromatography. The vitamin D sulfate fraction is obtained from a plasma specimen (three volunteers) by the combined use of a Sep-Pak C18 cartridge, for solid-phase extraction, and a lipophilic gel (piperidinohydroxypropyl Sephadex LH-20), for ion-exchange chromatography. 25-Hydroxyvitamin D3 3-sulfate is identified in the examined three specimens in two ways: its chromatographic behavior and that of its fluorescent labeled derivative using 4-[4-(6-methoxy-2-benzoxazolyl)phenyl]-1,2,4 triazoline-3,5- dione; and data obtained from the solvolysis reaction. PMID- 7876375 TI - Non-invasive prenatal diagnosis using fetal cells in maternal blood. PMID- 7876376 TI - Human papillomaviruses and cervical neoplasia. I. Classification, virology, pathology, and epidemiology. PMID- 7876377 TI - p53 immunoreactivity in cervical intraepithelial neoplasia and non-neoplastic cervical squamous epithelium. AB - AIMS: To determine the pattern of p53 immunoreactivity in cervical squamous epithelium and to investigate the relation between p53 immunostaining and human papillomavirus (HPV) infection. METHODS: Immunocytochemistry for p53 was performed in 65 specimens of formalin fixed, paraffin wax embedded cervical tissue using a polyclonal antibody against recombinant p53. Microwave oven heating was used for antigen retrieval. Eight normal biopsy specimens, eight cases with histological features of HPV infection, and 49 cases of cervical intraepithelial neoplasia (CIN) were examined. Thirty one cases of CIN were examined. Thirty one cases of CIN were examined for evidence of HPV infection using in situ hybridisation with probes directed against wide spectrum HPV, HPV 16 and HPV 18. RESULTS: p53 immunoreactivity was seen in seven of eight (87%) of specimens with histological features of HPV infection, five of eight (62%) normal specimens, 13 of 22 (59%) CIN III, three of 14 (21%) CIN II and five of 13 (38%) CIN I specimens. The numbers of positive nuclei were small in cases of CIN and the location of positive nuclei within the epithelium paralleled the degree of dysplasia. Eleven of 15 (73%) CIN specimens which were immunoreactive for p53 yielded a positive signal for HPV by in situ hybridisation. A positive signal for HPV was also seen in 10 of 16 (63%) of CIN specimens in which p53 staining was absent. CONCLUSIONS: p53 immunoreactivity can be demonstrated in a small proportion of cells in the cervical squamous epithelium in a significant proportion of cases of CIN. This immunoreactivity seems to be independent of the presence of HPV, as assessed by in situ hybridisation. p53 immunoreactivity also occurs in non-neoplastic cervical squamous epithelium with a pattern of distribution within the epithelium which differs from that seen in CIN. Antigen retrieval by microwave oven heating enhances p53 immunostaining and may result in visualisation of cellular p53 in the absence of mutation. PMID- 7876378 TI - Role of human papillomavirus in determining the HLA associated risk of cervical carcinogenesis. AB - AIMS: To investigate the role of human papillomavirus (HPV) in the association between HLA DQw3 and squamous cell cancer of the cervix (SCCC). METHODS: Tissue from 194 cervical samples, ranging from normal, through cervical intraepithelial neoplasia, to SCCC, were typed for HPV by amplification of the L1 gene using degenerate consensus primers, followed by oligonucleotide probing. HLA DQw3 typing was undertaken in the same samples using a new PCR amplification system using primers common to all DQ loci, followed by restriction digestion with Mlu 1 to differentiate HLA DQw3 types--null, heterozygous, and homozygous. The data were analysed using chi 2 analysis and by calculating relative risks with the 95% confidence interval. RESULTS: Samples (n = 188) were successfully typed for HPV and 177 were typed for HLA DQw3. There was a nonsignificant rise in the prevalence of HLA DQw3 in SCCC (64.3%) compared with the group with normal histology (53.2%). Analysis of the prevalence of HLA DQw3 on the basis of HPV infection rather than histology showed that 63 of 95 (66.3%) of the HPV positive samples contained HLA DQw3 alleles, compared with 39 of 78 (50.0%) of the HPV negative samples (chi 2 4.06; p < 0.05). CONCLUSIONS: There was a significant association between HLA DQw3 and cervical HPV infection. This may be because people with HLA DQw3 are less able to mount an effective immune response to HPV, which predisposes them to the development of SCCC. PMID- 7876379 TI - Diagnosis of pancreatic lesions using fine needle aspiration cytology: detection of K-ras point mutations using solid phase minisequencing. AB - AIMS: To improve the diagnostic value of fine needle aspiration biopsy of pancreatic lesions using a simple mutation detection method based on the polymerase chain reaction (PCR). METHODS: Fine needle aspirates from 21 suspected pancreatic lesions were analysed for K-ras codon 12 point mutations using solid phase minisequencing. RESULTS: A point mutation in codon 12 of the K-ras gene was detected in 14 of 17 cases of pancreatic carcinoma. No false positive results were recorded. The concordance of the result with routine cytology was 78%. All patients diagnosed as having malignant disease on cytology also had a K-ras point mutation. Additional information on the presence of malignancy was obtained using molecular genetic analysis in two cases. CONCLUSIONS: PCR based minisequencing is a promising method for the analysis of cytological material. K-ras point mutation analysis was modified to enable it to be carried out in a clinical laboratory. Advantages of the method include its simplicity and speed. Adequate sampling guidance is important but analysis can be performed even with small amounts of cellular material. PMID- 7876380 TI - In vitro bromodeoxyuridine labelling of renal biopsy specimens: correlation between labelling indices and tubular damage. AB - AIMS: To examine the correlation between bromodeoxyuridine (BrdU) labelling indices (LI) and tubular damage in renal biopsy specimens; to evaluate the diagnostic and prognostic potential of measuring cell proliferation in a variety of renal lesions. METHODS: In vitro BrdU labelling of renal biopsy specimens was undertaken and labelled cells were detected in routinely fixed, paraffin wax embedded sections by immunohistochemistry. The BrdU LI were calculated as percentages for the three types of tubular cells--proximal and distal convoluted tubules and medulla (LI/PCT, LI/DCT, LI/Med)--and a total tubular BrdU LI (LI/Tub) was also calculated for each biopsy specimen. Histological features indicative of tubular damage were also scored and a total tubular damage score obtained for each biopsy specimen. RESULTS: The one hour labelling process did not affect tissue morphology or impede subsequent diagnosis. Four biopsy specimens were obtained from three renal transplant recipients. Diagnosis of 19 non-transplant biopsy specimens revealed a variety of renal lesions. Total tubular damage scores ranged from 0 to 25 and the LI/Tub ranged from 0 to 3.68% in all 23 biopsy specimens. Analyses of variance showed highly significant correlations between the total tubular damage score and both LI/Tub (p = 0.004) and LI/PCT (p = 0.004); a weaker correlation was found between the total tubular damage score and LI/DCT (p = 0.013). CONCLUSIONS: A correlation was found between tubular damage and BrdU LI. This was most clearly seen in the proximal tubules. However, as the study was limited to a few examples of specific forms of glomerular or interstitial disease, firm conclusions about the value of BrdU labelling in routine diagnosis and prognosis could not be drawn. PMID- 7876381 TI - Electrophoretic study of the physico-chemical characteristics of Bence-Jones proteinuria and its association with kidney damage. AB - AIM: To identify a physico-chemical criterion, or set of criteria, explaining and possibly predicting the nephrotoxic behaviour of Bence-Jones proteins (BJP). METHODS: The electrophoretic mobility and isoelectric point (pI) of 92 BJP isolates were determined using various electrophoresis procedures on polyacrylamide gel. The proportions of monomers and dimers were determined using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE) in 58 cases. PAGE data for 10 BJP isolates were used to construct Ferguson plots and titration curves. RESULTS: The distribution of electrophoretic mobility and pI values was bimodal and showed a positive correlation when the pI was above 6. The values of these two parameters in 22 patients with renal impairment were not significantly different from those in the patients without renal impairment, and the statistical analysis showed no predictive value for the onset of renal impairment. However, patients excreting the lambda light chain isotype had a 2.8 fold higher risk of developing renal impairment compared with the other patients. Studies of the charge variation of the protein with pH indicated three types of behaviour, suggesting that the charge of BJP is highly variable at physiological pH. CONCLUSION: It is important to study not only the positivity or negativity of the BJP charge at a given pH, but also its intensity. The study of the BJP titration curves in patients with renal impairment suggests that a low charge at physiological urinary pH could predict renal impairment. PMID- 7876382 TI - Transforming growth factor beta 1 as a prognostic factor in pulmonary adenocarcinoma. AB - AIMS: To evaluate the efficacy of transforming growth factor beta (TGF-beta) for the prognosis of pulmonary adenocarcinoma. METHODS: TGF-beta was detected immunohistochemically using the avidin-biotin-peroxidase complex technique in resected pulmonary adenocarcinomas from 88 patients. RESULTS: Of the 88 patients, 39 were TGF-beta negative and 45 TGF-beta positive. The five year survival rate was 56% for the TGF-beta negative and 16% for the TGF-beta positive group. CONCLUSIONS: TGF-beta can be used as a prognostic factor in pulmonary adenocarcinoma. PMID- 7876383 TI - Use of three immunological techniques for the detection of Toxoplasma spIgA antibodies in acute toxoplasmosis. AB - AIMS: To assess the performance and efficacy of three immunological techniques for the detection of Toxoplasma specific IgA antibodies in acute toxoplasmosis. METHODS: The following techniques were used to examine 128 serum samples (51 cases of acute toxoplasmosis, 50 cases of heterologous infections, and 27 healthy controls): direct enzyme linked immunosorbent assay (ELISA), antibody capture ELISA, and antibody capture agglutination. RESULTS: Direct ELISA had a sensitivity of 98% and a specificity of 97%, antibody capture ELISA of 100% and 99%, respectively, and antibody capture agglutination had sensitivity and specificity of 100%. CONCLUSIONS: All three immunological techniques performed well with similar efficacy. Detection of Toxoplasma specific IgA antibodies is a useful diagnostic marker for acute toxoplasmosis. PMID- 7876384 TI - Ethnic differences in lipid and lipoprotein metabolism in pregnant women of African and Caucasian origin. AB - AIMS: To investigate differences in serum lipid, lipoprotein and apolipoprotein concentrations in pregnant women of different ethnic origin. METHODS: Serum lipid, lipoprotein and apolipoprotein concentrations were measured in 232 women (114 Caucasians, 118 Africans/Afro-Caribbeans), who presented consecutively for screening for gestational diabetes in the third trimester of pregnancy. RESULTS: African/Afro-Caribbean pregnant women had lower serum concentrations of total cholesterol, low density lipoprotein cholesterol, triglycerides, and apolipoprotein B and higher high density lipoprotein cholesterol and Lp(a) lipoprotein concentrations compared with Caucasian women. Apolipoprotein A1 concentrations were similar in the two groups. The differences were not attributable to differences in weight, age, parity, or postload plasma glucose levels. CONCLUSION: Ethnic origin is an important determinant of serum lipid, lipoprotein and apolipoprotein concentrations during pregnancy. PMID- 7876385 TI - EB9, a new antibody for the detection of trophozoites of Pneumocystis carinii in bronchoalveolar lavage specimens in AIDS. AB - AIM: To prepare a monoclonal antibody (EB9) against the trophozoite form of Pneumocystis carinii and to test its efficacy for detecting infection with this organism. METHOD: The sensitivity and specificity of the EB9 antibody were assessed by comparing it with other conventional stains (Papanicolaou, Giemsa and Grocott) and 3F6 antibody in 33 bronchoalveolar lavage specimens from HIV positive patients suspected of having P carinii pneumonia. RESULTS: P carinii infection was detected in 15 of 33 patients. In 14 cases the organism was detected by two or more of the staining methods used; however, EB9 failed to detect infection in two cases which were positive by other staining techniques. In one case P carinii infection was detected by EB9 only. CONCLUSION: The results of this study suggest that P carinii infection in the lung may occur in two forms: the cyst form and the trophozoite form, which may explain the observed variation in response to treatment. PMID- 7876386 TI - Hepatic expression of tumour necrosis factor-alpha in chronic hepatitis B virus infection. AB - AIM: To determine the hepatic expression of tumour necrosis factor-alpha (TNF alpha) in patients with chronic hepatitis B virus (HBV) infection. METHODS: Frozen liver biopsy sections from 19 patients with chronic HBV infection were studied, 12 of whom were HBeAg positive and 10 serum HBV DNA positive. Hepatic expression of TNF alpha was determined using immunohistochemistry. RESULTS: Only infiltrating mononuclear cells showed immunoreactive staining for TNF alpha (median 2, range 0-3; n = 19) which appeared as diffuse positive staining material in the cytoplasm. Patients with active liver disease, assessed histologically and biochemically, had a higher level of expression, both in the number of TNF alpha positive cells and the proportion of TNF alpha positive infiltrating mononuclear cells. There was no correlation between the expression of TNF alpha and serological parameters of viral infection (HBeAg and HBV DNA status and HBV DNA concentrations). CONCLUSION: Hepatic expression of TNF alpha is increased in chronic HBV infection and is related to the activity of liver disease and not to the level of HBV replication. PMID- 7876388 TI - False positive immunoreaction in products of conception. AB - False positive immunostaining for cytomegalovirus in products of conception was revealed using an avidinbiotinylated peroxidase complex. The cause was shown to be endogenous biotin. The use of a non-avidin-biotin method avoided the problem. PMID- 7876387 TI - Blood stained cerebrospinal fluid responsible for false positive reactions of latex particle agglutination tests. AB - The accuracy of the latex particle agglutination test (LPAT) was assessed in blood stained cerebrospinal fluid (CSF) specimens from 166 paediatric patients, aged from three months to 13 years. A commercial LPAT kit was used to detect Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis A, B, and C soluble antigens. Culture of CSF specimens was used as the standard and all laboratory procedures were performed blind. The mean CSF erythrocyte count was 66,406 cells/mm3 in the cases and 11,560 cells/mm3 in the controls. The sensitivity and the specificity of LPAT were 83.8 and 94.0%, respectively, suggesting that LPAT is a useful diagnostic tool even in blood stained CSF specimens. PMID- 7876389 TI - Comparison of two automated quantitative immunoassays for the determination of C reactive protein concentrations. AB - Two quantitative, automated methods for the determination of C reactive protein (CRP) were compared: turbidimetry (Cobas Fara II, Roche, Welwyn Garden City, UK) and fluorescence polarisation TDx, Abbott, Wokingham, UK). One hundred and twenty routine serum samples submitted for measurement of CRP were tested using both procedures. The results were compared using regression line analysis and showed a high degree of correlation (r2 = 0.99, X coefficient = 1.01, constant = 0.11). C reactive protein can be accurately measured using the automated turbidimetric method which can be recommended as an alternative to fluorescence polarisation. PMID- 7876390 TI - Isolated testicular vasculitis mimicking a testicular neoplasm. AB - A 19 year old man presented with unilateral testicular swelling and pain. An initial diagnosis of epididymo-orchitis was modified to a presumed testicular neoplasm following ultrasonography. The final diagnosis of isolated testicular vasculitis was established following histological examination of the orchidectomy specimen. Staining for antineutrophil cytoplasmic antibodies was negative. Despite immunosuppressive treatment, the patient developed further symptoms affecting the remaining testis one year later. He responded well to an increase in immunosuppressive therapy and has remained asymptomatic 18 months from diagnosis. Symptomatic vasculitis confined to the testis is extremely rare, but must be considered in the differential diagnosis of testicular swelling and may be the presenting feature of a systemic vasculitis such as polyarteritis nodosa. The risk of progression to systemic disease in such cases is unknown. Immunosuppressive therapy must be considered carefully and long term follow up is important. PMID- 7876391 TI - Lymphocytic gastritis, gastric adenocarcinoma, and primary gastric lymphoma. AB - A series of primary gastric lymphomas and adenocarcinomas was reviewed to assess the prevalence of lymphocytic gastritis in these conditions. Lymphocytic gastritis was more prevalent in patients with gastric adenocarcinoma (16 of 130 cases; 12.3%) and primary gastric lymphoma (six of 45 cases; 13.7%) than in unselected patients undergoing endoscopy (0.83-2.5%). This suggests that these two disparate gastric tumours may share an immunological dysfunction or a common pathogenesis, and this is of interest given that Helicobacter pylori is thought to have a role in the evolution of gastric adenocarcinoma and lymphoma. PMID- 7876393 TI - Pediatric medication errors: predicting and preventing tenfold disasters. AB - Tenfold errors in pediatric doses are not uncommon. Because the needed volume of stock solution is generally small, even a tenfold higher volume may still appear deceivingly normal. Such errors are much less likely to occur in adults, because it would result in unacceptably large volumes of stock solution. Other sources of tenfold errors are communication difficulties with parents and illegible writing of orders by physicians. Testing health professionals may identify subgroups of individuals who are prone to commit such errors. Independent double checking of calculations and a mechanism to resolve disagreement is being practiced in most academic institutions. Transition to patient's unit dose is likely to decrease calculation errors, because pharmacists commit fewer errors. Hazardous drugs that are not required on a stat basis should be removed from the wards. PMID- 7876392 TI - Drug chirality: on the mechanism of R-aryl propionic acid class NSAIDs. Epimerization in humans and the clinical implications for the use of racemates. AB - This review summarizes and comments on the current understanding of both the biochemical and clinical implications of the epimerization of R-aryl propionic (APA) class (1) nonsteroidal anti-inflammatory agents (NSAIDs) to S-enantiomers in humans. This article focuses principally on rac-ibuprofen and its enantiomers. In the United States, five commercialized NSAIDs are APAs. Only two of them, rac ibuprofen and rac-fenoprofen, are subject to significant epimerization in humans. The remaining three, rac-flurbiprofen, rac-ketoprofen, and S-naproxen, are not of interest in this context. PMID- 7876394 TI - Estimation of pharmacokinetic parameters for simulations of time courses of drug concentrations after oral administration. AB - Simulations of time courses of drug concentrations after oral administration are frequently hampered by the lack of pharmacokinetic parameters after oral dosing. This article presents methods by which to estimate such parameters from pharmacokinetic parameters after intravenous dosing and knowledge of time of peak concentration and bioavailability after oral dosing. The application of these approaches enables the generation of meaningful graphic simulations of time courses of drug concentrations after oral administration that can have educational and illustrative uses. PMID- 7876395 TI - Phase I study of E1077, a novel parenteral cephem antibiotic. AB - The safety and pharmacokinetics of E1077, a new injectable cephem antibiotic, were evaluated in healthy male adult volunteers. In the single-dose studies, 100, 250, 500, 1,000, and 2,000 mg of E1077 were administered by intravenous infusion at a constant rate for 60 minutes, then 1,000 mg of the drug by intravenous infusion at a constant rate for 5 minutes. The Cmax were 6.4, 15.7 +/- 12.0, 34.7 +/- 4.6, 63.2 +/- 4.6, 142.7 +/- 5.6, and 131.6 +/- 36.0 (means +/- SD) micrograms/mL, respectively, and the Cmax and AUC increased linearly with the dose. Plasma concentration-time curves were well described by a two-compartment open model. The plasma elimination half life of the drug was 1.88 +/- 0.15 hours. The mean urinary recovery within the first 24 hours was 94.1 +/- 5.1% of the dose. In the multiple-dose study, 2,000 mg of E1077 was intravenously administered at a constant rate over 60 minutes every 12 hours for 4.5 days (a total of nine times). The Cmax after the first and ninth doses were 134.0 +/- 17.4 and 135.5 +/- 15.5 micrograms/mL, respectively, and trough levels in day 1 and day 5 (at 12 hours after the first and ninth administration, respectively) were 2.2 +/- 0.8 and 1.9 +/- 0.4 micrograms/mL, respectively. No accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in the urinary recoveries between the single- and multiple-dose regimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876396 TI - Pharmacokinetics of intravaginal metronidazole gel. AB - The pharmacokinetics of a single 500 mg oral dose of metronidazole and 5 g of 0.75% metronidazole intravaginal gel (37.5 mg metronidazole) were compared in 12 adult volunteers in a randomized crossover manner. Serial serum samples were collected over a 48-hour period and analyzed for metronidazole and hydroxymetronidazole. Metronidazole serum concentrations after intravaginal administration were only 2% of concentrations seen with the standard 500-mg oral dose. The dose-adjusted maximum serum concentration (898 +/- 121 ng/mL vs. 237 +/ 69 ng/mL) and area under the serum concentration-time curve (9362 +/- 2873 ng * hr/mL vs. 4977 +/- 2671 ng * hr/mL) were significantly greater for the oral versus intravaginal dose of metronidazole. The time to reach maximum concentration (1.4 +/- 0.6 hr vs. 8.4 +/- 2.2 hr) was significantly shorter for the oral compared with the intravaginal dose. The mean bioavailability for the intravaginal gel was 56%. Our results show that the 0.75% gel formulation may offer the advantage of fewer systemic adverse effects compared with other formulations for the treatment of bacterial vaginosis. PMID- 7876397 TI - Pharmacokinetics of cefodizime in volunteers with normal or impaired renal function. AB - The pharmacokinetics of single, 1- or 2-g intravenous doses of cefodizime were studied in subjects with normal, impaired renal function or requiring chronic hemodialysis. Drug concentrations were measured using high-performance liquid chromatography. Forty-five subjects (20 with creatinine clearance of > or = 90 mL/min, 15 with creatine clearances between 5 and 89 mL/min, and 10 requiring chronic hemodialysis) were studied. The concentration-time curve of cefodizime was best represented by an open two-compartment model. The elimination half-lives in subjects with normal (Group 1) and impaired renal function (Group 2) or requiring chronic hemodialysis (Group 3) were 4.14 +/- 1.55, 5.10 +/- 2.24, and 10.1 +/- 6.01 hours, respectively (Group 3 versus 1 or 2, P < .05; Group 1 versus 2, P > .05). The total body (serum) clearances in the same groups were 3 +/- 0.52, 2.22 +/- 0.61, and 0.99 +/- 0.33 L/hour, respectively (Group 1 versus 2 or 3, P < .05; Group 2 versus 3, P < .05). Although renal function has an effect on the pharmacokinetics of cefodizime, its effect on the elimination half life is marginal in subjects with creatinine clearance of more than 25 mL/min. In individuals with more severe renal impairment or those requiring chronic hemodialysis, dosage adjustment would be required. PMID- 7876398 TI - Pharmacokinetics of sparfloxacin in humans after single oral administration at doses of 200, 400, 600, and 800 mg. AB - The pharmacokinetics of sparfloxacin at oral doses of 200, 400, 600, and 800 mg were studied in 12 healthy volunteers in a randomized double-blind crossover study. Each dose administration was separated by a 1-week washout period. Plasma and urine samples were collected up to 120 hours postdosing, for determination of free and total (free plus glucurono-conjugated) sparfloxacin levels by high performance liquid chromatography assay and ultraviolet detection. Mean Cmax values ranged from 705 +/- 158 to 1966 +/- 620 ng/mL for the 200 to 800 mg doses, at median tmax ranging from 4 to 5 hours. A slight decrease of sparfloxacin bioavailability with increasing dose was observed because AUC was 87% to 88% of the expected area when the dose was doubled. The elimination half-life values were constant over the dose range (with values ranging from 18 to 21 hours) as well as the renal clearance. The metabolic ratio conjugated/free drug was not modified by increasing dose. PMID- 7876399 TI - Concentrated potassium chloride infusions in critically ill patients with hypokalemia. AB - Although concentrated infusions of potassium chloride commonly are used to treat hypokalemia in intensive care unit patients, few studies have examined their effects on plasma potassium levels. Forty patients with hypokalemia were given infusions of 20 mmol of potassium chloride in 100 mL of normal saline over 1 hour; 26 patients received the infusions through the central vein and 14 patients through the peripheral vein. Plasma potassium ([K]p) was measured at 15-minute intervals during and after the infusion in 31 patients. delta K was defined as the difference between each potassium determination and baseline plasma potassium concentration. Continuous electrocardiographic recording was carried out during the infusion and during the 1-hour period immediately preceding the infusion. Mean baseline [K]p was 2.9 mmol/L and all subsequent plasma concentrations significantly increased from baseline. Mean peak [K]p was 3.5 mmol/L, [K]p (1 hour postinfusion) was 3.2 mmol/L, and mean postinfusion delta K was 0.48 mmol/L (range -0.1-1.7 mmol/L). Arrhythmias, changes in cardiac conduction intervals, and other complications did not occur. The frequency of premature ventricular beats decreased significantly during the infusion compared with that of the control period. The high concentration (200 mmol/L) and rate of delivery (20 mmol/hr) of the potassium chloride infusions were well tolerated, decreased the frequency of ventricular arrhythmias, and did not cause transient hyperkalemia. PMID- 7876400 TI - Intravenous torsemide as adjunctive therapy in patients with acute pulmonary edema. AB - The safety and efficacy of intravenous (i.v.) torsemide as adjunctive therapy for acute cardiogenic pulmonary edema was evaluated. Thirteen patients were treated with i.v. torsemide and six patients, with i.v. furosemide, as a positive control. Doses of torsemide, 20 mg or 40 mg, and furosemide, 40 mg or 80 mg, were administered initially. The dose was titrated as necessary over the next 24 hours. In patients who received i.v. torsemide, median fractional sodium excretion significantly increased from 2.88% (0.04-10.1%) at baseline to 6.76% (0.71-11.6%) at peak (P = 0.0342). Hourly urine volume increased from 134 mL (25 400 mL) to 375 mL (145-790 mL) (P = 0.0034). Torsemide administration resulted in a significant improvement in both pulmonary rales and orthopnea. None of the patients experienced serious adverse events or required withdrawal from the study. These results suggest that i.v. torsemide is an effective and well tolerated diuretic in patients with acute cardiogenic pulmonary edema. PMID- 7876401 TI - Hematologic disposition of hydroxychloroquine enantiomers. AB - Hydroxychloroquine (HCQ) is a racemic antiarthritic agent that has a long half life (t1/2) in plasma and accumulates in blood cells. To study the relationships between HCQ concentrations in plasma, serum, and whole blood and to determine the optimal blood fraction to use for therapeutic drug monitoring of the drug, we studied the relative distribution of the HCQ enantiomers in various fractions of human blood under in vivo and in vitro conditions. Substantially greater concentrations of both enantiomers were found in serum as compared with plasma because of release via platelet activation. After in vitro incubations of the separated blood cells with HCQ, high concentrations of both enantiomers were found in leukocytes, and low concentrations in erythrocytes and platelets; the R:S ratio in vitro was near unity in all of the cells examined. Unlike the in vitro cellular uptake, the concentrations of HCQ in vivo were significantly lower and stereoselective (R:S ratio = 2). There was almost no drug in the polymorphonuclear cells (PMN) in vivo, despite a substantial uptake in vitro after incubation of separated cells. The enantiomeric (R:S) ratio in the urinary excretion of the enantiomers was significantly correlated with that in plasma. The plasma-protein binding of the enantiomers was stereoselective and complimented the cellular uptake findings; the unbound fraction was dependent on the plasma concentrations of alpha 1-acid glycoprotein, but not albumin. Although concentrations in whole blood correlated well with those in lymphocytes and monocytes (the proposed site of HCQ action), stronger correlations were found between concentrations in serum and in the mononuclear cells. PMID- 7876402 TI - Comparative effects of nabumetone, sulindac, and indomethacin on urinary prostaglandin excretion and platelet function in volunteers. AB - Nonsteroidal antiinflammatory drugs differ with respect to their effects on prostaglandin metabolism in various tissues, a property that may be partly responsible for some of the differences in the pharmacologic activities and side effect profiles that are associated with their use. The effects of nabumetone on urinary prostaglandin excretion have not been reported. Fourteen healthy females, age 21-43 years, were treated with nabumetone (NAB) 1000 mg daily, sulindac (SUL) 200 mg every 12 hours, and indomethacin (IND) 50 mg every 12 hours for 7 days in a randomized period-balanced crossover study. The effects of drug treatment on urinary prostaglandin excretion (PGE2, 6-keto-PGF1 alpha, PGF2 alpha, thromboxane [TX] B2) and platelet function (collagen-induced whole blood platelet aggregation [CIPA] and template bleeding time) were determined on day 1 and day 7. For each treatment regimen, mean baseline urinary PG excretion values were comparable for each prostanoid, but the pattern of excretion differed in response to each drug. Treatment with NAB significantly increased the urinary excretion rates of PGE2 and PGF2 alpha, but 6-keto-PGF1 alpha and TXB2 excretion were unchanged. IND treatment did not result in a significant change in PGE2 excretion but did significantly reduce urinary 6-keto-PGF1 alpha and TXB2 excretion rates. Reduced excretion of PGF2 alpha was observed on both study days during treatment with IND and SUL. SUL treatment also resulted in increased urinary PGE2 excretion while significantly reducing 6-keto-PGF1 alpha excretion on day 7. Significant differences were observed between the NAB and SUL regimens with respect to PGF2 alpha excretion and between the NAB and SUL regimens for PGE2, PGF2 alpha, 6-keto PGF alpha 1 (on day 1 only) and TXB2 (on day 1 only). Neither NAB nor SUL caused inhibition of CIPA or bleeding time although platelet aggregation was inhibited during IND treatment. That NAB treatment was neither associated with alterations in platelet function nor decreases in the urinary excretion of the vasodilatory prostaglandins, PGE2 and 6-keto-PGF1 alpha, suggests that NAB possesses renal sparing properties. PMID- 7876403 TI - Pilot study of the pharmacokinetics of methylprednisolone after single and multiple intravenous doses of methylprednisolone sodium succinate and methylprednisolone suleptanate to healthy volunteers. AB - The pharmacokinetics of methylprednisolone were evaluated in 29 healthy volunteers after multiple intravenous doses of methylprednisolone sodium succinate or the novel prodrug, methylprednisolone suleptanate. Subjects were assigned randomly to one of four treatment groups (40, 100, 250, or 500 mg) and then randomly assigned to receive either the sodium succinate or suleptanate prodrugs. Doses were administered every 6 hours for 48 hours. Plasma and urine were assayed for methylprednisolone and unchanged prodrug using HPLC methods. Methylprednisolone pharmacokinetics exhibited both a dose and time dependency, which was similar for administration of both prodrugs. After first-dose administration, mean clearance increased from 19.5 L/hr for 40-mg doses to 27.7 L/hr after 500-mg doses of the sodium succinate ester, and from 20.1 to 31.7 L/hr after the suleptanate ester. After multiple dosing, mean clearance values increased from 31.1 to 44.7 L/hr for sodium succinate dosing, and from 31.5 to 46.0 L/hr for suleptanate dosing. Apparent systemic clearance values determined after multiple dosing were 1.5- to 1.8-fold greater than corresponding first-dose values. No dependence on time was apparent for any prodrug pharmacokinetic parameter. These data suggest that the dose dependency of methylprednisolone pharmacokinetics is related to dose-dependent prodrug hydrolysis, whereas the time dependence possibly reflects auto-induction of methylprednisolone metabolism. Based on comparison of methylprednisolone pharmacokinetic parameters derived for each prodrug, methylprednisolone suleptanate resulted in a faster and slightly more efficient conversion to methylprednisolone than methylprednisolone sodium succinate. PMID- 7876404 TI - Angiotensin-converting enzyme inhibitors and cough: a prospective evaluation in hypertension and in congestive heart failure. AB - Angiotensin-converting enzyme inhibitors (ACE-I) have become the mainstem of antihypertensive therapy and first-choice agents for vasodilatation in congestive heart failure (CHF). A typical dry cough is the main cause for discontinuation of ACE-I therapy. Data about the incidence, course, and clinical significance of this side effect are conflicting. This study determined the incidence of cough in ACE-I treated patients with hypertension and with CHF and to appreciate its clinical significance; 268 ACE-I treated patients, 164 with hypertension and 104 with CHF were prospectively followed for at least 1 year and specifically questioned about cough and other side effects. In those in whom cough developed, a second and then a third ACE-I were tried. Cough developed in 50 (18.6%) of the 268 patients; 23 patients with hypertension (14%) had coughs 24.7 +/- 17.1 (SD) weeks after initiation of therapy; 27 patients with CHF (26%) had coughs 12.3 +/- 12 (SD) weeks after the start of ACE-I therapy (P = 0.005). All but three patients had coughs also on the second and third ACE-I. The time from the beginning of therapy to the onset of cough was significantly shorter with the second than the first drug. ACE-I agents had to be discontinued in 50% of the patients in whom coughs developed, most of them in the CHF group. In the others, cough was well tolerated or disappeared during subsequent months. The incidence of cough, which necessitated discontinuation of ACE-I treatment, was 4% among patients with hypertension and 18% among patients with CHF (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876405 TI - Comparison of the inhibition of dietary fat absorption by full versus divided doses of orlistat. AB - Orlistat is a potent and selective inhibitor of gastrointestinal lipases. The drug is designed for the treatment of obesity. The effect on dietary fat absorption of orlistat after administration of divided doses spread over 2 hours from mid-meal, in comparison with that after administration of a full dose mid meal, was investigated in a randomized, single-blind study including 16 hospitalized healthy males. After a 5-day run-in, to accustom the subjects to a diet of 2350 kcal and 76 g fat per day and to establish baseline fecal fat excretion, subjects received, in two parallel groups of eight over 8 days, three times a day 80 mg orlistat at mid-meal, and placebo at mid-meal and 0.5, 1, and 2 hr after mid-meal (group A), or placebo at mid-meal, and 20 mg orlistat at mid meal and 0.5, 1, and 2 hr after mid-meal (group B). Feces were collected to measure total fat excretion. The mean (SD) of fecal fat in percent of dietary fat, after deduction of pretreatment fecal fat, was (%) 36.1 (4.2) and 37.0 (9.3) in groups A and B, respectively. Changing the mode of administration of orlistat, within the dose regimens investigated, does not affect its pharmacologic efficacy. PMID- 7876406 TI - Diuretic effects, pharmacokinetics, and safety of a new centrally acting kappa opioid agonist (CI-977) in humans. AB - The diuretic effects, pharmacokinetics, and safety of CI-977, a new centrally acting selective kappa-opioid agonist, were determined in 16 healthy subjects. Subjects received single intramuscular doses of CI-977 (5, 15, or 25 micrograms) or placebo 1 week apart according to a randomized, double-blind, placebo controlled, four-period, crossover design. Serial blood and urine specimens were collected after each dose. Significant dose-related decreases in negative free water clearance and urine osmolality and increases in urine volume were observed after administration of 15- and 25-micrograms doses of CI-977. CI-977 had no effect on urine electrolyte excretion or serum antidiuretic hormone. Absorption of CI-977 was rapid with individual tmax values ranging from 0.17 to 1.5 hours. Cmax and AUC(0-infinity) increased proportionally with dose. Individual elimination half-life values ranged from 0.6 to 3.3 hours and were independent of dose. Changes in free water clearance were related to CI-977 Cmax (r2 = 0.29, P = 0.0001) and AUC(0-4 hr) (r2 = 0.32, P = 0.0001) values. The most frequently reported adverse events after CI-977 administration were dizziness, fatigue, paresthesia, headache, vasodilatation (facial flushing), emotional lability, high feeling, and abnormal thinking. The frequency and intensity of adverse events increased with increasing CI-977 dose. In conclusion, CI-977 Cmax and AUC(0 infinity) increased in proportion to dose over the range of 5 to 25 micrograms; decreases in negative free water clearance were related to CI-977 dose and Cmax and AUC(0-4 hr) values; and the frequency and intensity of adverse events increased with increasing CI-977 dose. PMID- 7876407 TI - Bound-morpheme skills in the oral language of school-age, language-impaired children. AB - Bound-morphine skills of school-age, language-impaired (LI) children were explored with three tasks designed to assess multiple dimensions of this component of language. Ten English-speaking, school-age LI children (Mean age: 10:3) and ten children with normal language (Mean age: 9:9) served as subjects. A two-way analysis of variance revealed significant group differences. Fisher a priori testing documented significant group differences for a measure of English bound-morpheme skill levels, a measure of ability to generalize English bound morphemes to novel words, and a measure of ability to learn novel bound-morphemes attached to novel words. The findings indicate that core features of developmental language impairment in preschool children--poor ability to learn, to use, and to generalize bound-morphemes--are also present in school-age, LI children. PMID- 7876409 TI - A longitudinal study of the emergence of phonemes in children with Down syndrome. AB - Articulation norms are typically used to measure sound acquisition and mastery in children with Down syndrome. The present longitudinal study examines the clinical records of 60 children with Down syndrome to evaluate phoneme acquisition and emergence. Results document the order of emergence of sounds in children with Down syndrome. Factors affecting emergence of sounds (e.g. oral motor skills) and difficulties in using a mastery model to evaluate speech sound acquisition in children with Down syndrome are explored. Clinical as well as research implications of the data are presented. PMID- 7876408 TI - Beginning signers' self-assessment of sign language skills. AB - Students enrolled in introductory manual communication classes demonstrated limited ability to assess their own communication skills. Questionnaires completed on the third day of class revealed that 70% of the students surveyed would attempt to interpret in a court of law if asked to do so. Although a fifty minute discussion concerning topics such as ASL, sign systems, and interpreter skills and ethics aided some students in putting their skills into perspective, 41% continued to overestimate their abilities at midterm. The reasons for the overestimation are not clear. Avenues for future research are suggested. PMID- 7876410 TI - Connectionist networks and language disorders. AB - Although neuropsychological localization constitutes the principal approach to the study of language disorders, there is reason to think it may not be entirely correct. Recent anatomical studies suggest that cognitive brain functions do not localize to precise anatomical locations. Connectionist (parallel distributed processing) approaches to the study of language, which emphasize the distributed nature of computational processes, may help explain the variability found in these anatomical studies, and provide a new way to approach the neurological study of language. This combined computational and empirical method focuses on the interplay between a computational model and the appropriate neurological, neuropsychological, and speech and language data, the whole couched in connectionist mechanisms that map naturally to what is known of the neurophysiological structure of the brain. This paper introduces the concepts of connectionist modeling, with emphasis on their use in understanding language disorders. PMID- 7876411 TI - Pulpo-dentinal complex revisited. AB - OBJECTIVES AND METHODS: The value of the concept of a pulpo-dentinal complex was assessed on human teeth treated according to the ISO test on biological evaluation. The teeth were extracted after 1 or 3 months and examined histologically. Biochemical and biological data available from the dental literature were also re-examined. RESULTS: During the early development of the tooth, pulp and dentine establish close links and form an undivided organ. However, examination of the tissues at later stages of development casts doubt on the validity of such a concept. Major differences are reviewed in this report between the cells (odontoblasts and heterogeneous pulpal cells) and extracellular matrix (collagens, non-collagenic proteins and phospholipids) located either in the odontoblast-dentine area or in the pulp. It seems also that clear-cut differences are detected during inflammatory and repair processes. CONCLUSION: It is concluded that, although the existence of a dentino-pulpal reaction cannot be denied, the concept of a pulpo-dentinal complex is an oversimplification and should be revisited. This may have implications in the evaluation of restorative treatments and in the design of a tissue repair strategy. PMID- 7876412 TI - Treatment times for three different types of veneer restorations. AB - In a longitudinal clinical trial the treatment times needed for the fabrication of veneer restorations (VRs) were recorded and analysed. Treatment times were determined for: (1) direct resin composite (DC), (2) indirect resin composite (IC) and (3) porcelain (P) veneer restorations and for two preparation designs, with and without incisal coverage. Significant effects on the treatment times were found for the factors: (1) type of VR, (2) operator, (3) number of VRs and (4) 'problems' in try-in phase for indirect VRs (IC- and P-VRs). The mean total time needed to perform one DC-VR was 46 min with a 95% confidence interval (c.i.) of 40-54 min, for one IC-VR 70 min (c.i. 60-82 min) and for one P-VR 62 min (c.i. 53-71 min). In the cases where more than one VRs were placed in one patient the times per VR were respectively: DC, 38 min (c.i. 34-44 min); IC, 59 min (c.i. 52 67 min); P, 49 min (c.i. 44-55 min). The results of this study are considered to be useful in further cost-benefit analyses. PMID- 7876413 TI - Effect of food and oral simulating fluids on structure of adhesive composite systems. AB - This work evaluates the degradation of three adhesive/composite systems (Tenure/Marathon One. Scotchbond Multi-Purpose/Z100 and Optibond/Herculite XRV) upon immersion in 75% ethanol solution and in an artificial saliva (Moi-Stir). Shear bond strength (SBS) and diametral tensile strength (DTS) specimens were employed for this study. For the SBS specimens, the bonded interface and composite were exposed to food and oral simulating fluids at 37 degrees C for up to 30 days. A similar control series was stored in air. DTS specimens were stored in 75% ethanol at 37 degrees C for up to 30 days. The SBS specimens were sheared to failure. Small quantities of bonding resin were removed from the tooth side of the fractured surface and from the non-fractured fractured end of the composite for Fourier transform infrared microscopic evaluation. Similar scrapings were taken from DTS specimen surfaces. The infrared absorbance intensity (AI) of the major peaks was measured as a function of storage time and ratioed against the aromatic C = C (1609.4 cm-1) peak. The data were analysed using ANOVA and the Tukey LSD test. The AI of major peaks was similar for the materials stored either in air or in Moi-Stir for all testing periods. Storage in ethanol caused the AI of aliphatic C = C (1638 cm-1) and of O-H (approximately 3500 cm-1) bonds to significantly decrease (30-50%) for specimens of bonding resin while the AI of C = O bonds (1730 cm-1) increased (60-120%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876414 TI - Effects of a commercial orthodontic debonding agent upon the surface microhardness of two orthodontic bonding resins. AB - The bonding techniques employed in orthodontic practice differ from those used in restorative dentistry for, upon the completion of treatment, the appliance is removed. This necessitates breaking the resin/enamel bond. Ideally a smooth, undamaged enamel surface free from all traces of bonding agent should result. Regrettably, however, this ideal is rarely achieved. This investigation assessed the effects of a commercial debonding agent (P-de-A, Oradent Ltd, Eton, Berks, UK), derived from peppermint oil, upon the surface microhardness of two orthodontic resins (Orthodontic Concise and Transbond, both 3M, St Paul, MN, USA). Twenty discs (10 mm diameter x 1.25 mm deep) of each resin were fabricated and, following 1 week's storage in distilled water at 37 degrees C, were allocated to application groups composed of four specimens. The mean initial surface hardness of each group was then determined prior to the application of P de-A for one of: 30, 60, 90, 120 and 180 s. The hardness was then remeasured. One way analyses of variance were performed upon the mean initial and final hardness data and revealed only a significant (P < 0.05) reduction in surface hardness following the 180 s application of P-de-A to Orthodontic Concise. We were therefore unable to find little evidence to suggest that the agent facilitates debonding by a softening mechanism and further work is required to elucidate the means whereby orthodontic debonding and 'clean-up' of residual composite, as reported by others, is facilitated. PMID- 7876415 TI - Influence of temperature and relative humidity on early bond strengths to dentine. AB - The effect of temperature and relative humidity (RH) on the early tensile bond strengths to bovine dentine of two bonding systems (Liner Bond System, and Scotchbond Multi-purpose), and an experimental system (KB-110) were tested. Two environmental conditions, room temperature (23 degrees C/50% RH) and oral temperature (30 degrees C/80% RH), were used in a controlled temperature and humidity chamber. Bond strengths were recorded immediately after, 10 min and 24 h following light curing. The tensile bond strengths did not vary between the two test conditions, but the mode of fracture was observed to change. The 30 degrees C/80% RH condition exhibited a slightly greater degree of adhesive type failures compared with the 23 degrees C/50% RH group. This was particularly so for the experimental system, indicating that different bonding systems may be more or less sensitive to changes in RH and temperature. Failures occurred partially or totally within the resin composite at the early test times, and it was concluded that the bond strengths of the systems tested tended to exceed the early cohesive strengths of the resin composite. PMID- 7876416 TI - Durability of resin bonds to a cobalt-chromium alloy. AB - Common nickel-chromium-beryllium alloys used for resin-bonded fixed partial dentures have possible health hazards due to leaching of nickel and beryllium. For resin-bonded restorations corrosion resistant cobalt-chromium alloys (CoCr) are a suitable alternative material without sacrificing physical properties. This study evaluated the bond strength and bond durability of new adhesive systems to a CoCr alloy. Plexiglas (acrylic) tubes filled with composite were bonded to CoCr alloy discs. Groups of 24 samples were bonded using six different bonding systems. Subgroups of eight bonded samples were stored in an isotonic artificial saliva solution (37 degrees C) either for 1 day, 30 days or 150 days. In addition the 30- and 150-days samples were subjected to 7500 or 37,500 thermal cycles, respectively. The bond strength of a conventional BisGMA composite (Twinlook) to sandblasted CoCr was significant lower than when using chemomechanical bonding systems and decreased continuously during the storage time of 150 days. The additional use of silane on the sandblasted alloy resulted in an insignificant increase in bond strength. Statistically significant higher and more durable bonds to CoCr alloy were achieved either with the combination of silica coating and use of the conventional BisGMA composite or with the combination of sandblasting and the use of a composite modified with a phosphate monomer (Panavia EX). In the latter systems, the bond strengths were mainly limited by the cohesive strength of the resin composites: partial adhesive failures were only observed for a tribochemical silica coating system. A new composite also containing the active phosphate monomer (Panavia TPN-S) exhibited a significant decrease in cohesive strength over time. PMID- 7876417 TI - Pharmacological control of periodontal disease. II. Antimicrobial agents. AB - Antimicrobial agents are of value in the management of certain types of periodontal disease, notably early onset, juvenile and refractory periodontitis. The diagnosis of these conditions is often made on clinical grounds but microbial sampling of the pocket flora is of value in determining the type of antimicrobial therapy. Routine systemic use of these drugs in the management of chronic adult periodontitis is contraindicated, and is no substitute for root surface debridement and thorough supragingival plaque control. Tetracyclines and metronidazole are the agents most frequently used in the management of periodontal disease. Both drugs can be given systemically or applied topically into the periodontal pocket. The latter route is preferred since the dose is reduced considerably, but the local tissue concentration is increased. The efficacy of local drug delivery is dependent upon the release kinetics of the drug from the delivery vehicle. Although local application can be time consuming, it reduces the risk of adverse reactions and drug interactions. The tetracyclines have the additional advantage of inhibiting collagenases. This property may facilitate repair and new attachment formation. Systemic metronidazole appears to be useful as an adjunct to conventional periodontal therapy. The combination of metronidazole 250 mg and amoxycillin 375 mg has been shown to be effective in the treatment of refractory periodontitis, including cases which are resistant to tetracycline. Clindamycin has also been used in the management of refractory periodontitis, but the unwanted effects of this drug must limit its systemic use for this purpose. PMID- 7876418 TI - A comparative study of three dental adhesives. AB - The shear bond strengths of three dental adhesives to dentine and a NiCrBe alloy were determined. Forty human third permanent molar teeth were ground to expose superficial dentine, to 20 of which P50 composite was bonded, using All-Bond 2 (n = 10) or Scotchbond 2 (n = 10). Alloy discs were bonded to the remaining 20 specimens, using either All-Bond 2 (n = 10) or Panavia Ex (n = 10). All specimens were stored at 37 degrees C. 100% RH, for 24 h. Testing was carried out using a shear jig at a cross-head speed of 1 mm min-1, following which a 0.5 mm increment was removed to expose middle dentine for further bond tests (n = 10 for each adhesive). Removal of a further 0.5 mm increment exposed 'deep' dentine for final dentine bond strength tests. Results were then aggregated for each substrate/adhesive combination (n = 30). Alloy/alloy bond strengths were determined after bonding alloy discs together using Panavia Ex (n = 30) or All Bond 2 (n = 30). Results were analysed using ANOVA and Weibull analysis. All-Bond 2 produced significantly greater and more reliable bond strengths to dentine than did either Scotchbond 2 or Panavia Ex. The bond strength of Scotchbond 2 and Panavia Ex to dentine was dependent upon the dentine depth whereas the bond strength of All-Bond 2 to dentine was independent of dentine depth. Alloy/alloy bond strengths were significantly greater when using Panavia Ex compared with All Bond 2. PMID- 7876419 TI - Tensile peeling failure of resin-bonded Ni/Cr beams: an experimental and finite element study. PMID- 7876420 TI - Implant hardware--science or commodity development? PMID- 7876421 TI - The molecular biology of initiation of tooth eruption. PMID- 7876422 TI - A compilation of partial sequences of randomly selected cDNA clones from the rat incisor. AB - The formation of tooth organs is regulated by a series of developmental programs. We have initiated a genome project with the ultimate goal of identifying novel genes important for tooth development. As an initial approach, we constructed a unidirectional cDNA library from the non-calcified portion of incisors of 3- to 4 week-old rats, sequenced cDNA clones, and classified their sequences by homology search through the GenBank data base and the PIR protein data base. Here, we report partial DNA sequences obtained by automated DNA sequencing on 400 cDNA clones randomly selected from the library. Of the sequences determined, 51% represented sequences of new genes that were not related to any previously reported gene. Twenty-six percent of the clones strongly matched genes and proteins in the data bases, including amelogenin, alpha 1(I) and alpha 2(I) collagen chains, osteonectin, and decorin. Nine percent of clones revealed partial sequence homology to known genes such as transcription factors and cell surface receptors. A significant number of the previously identified genes were expressed redundantly and were found to encode extracellular matrix proteins. Identification and cataloging of cDNA clones in these tissues are the first step toward identification of markers expressed in a tissue- or stage-specific manner, as well as the genetic linkage study of tooth anomalies. Further characterization of the clones described in this paper should lead to the discovery of novel genes important for tooth development. PMID- 7876423 TI - Temporal and spatial expressions of type XII collagen in the remodeling periodontal ligament during experimental tooth movement. AB - This study tested the hypothesis that the remodeling processes of adult periodontal ligament (PDL) reiterate the cellular and molecular events that occur sequentially during development. Type XII collagen has been implicated in the three-dimensional organization of the PDL extracellular matrix, and its expression has been restricted to the terminally differentiated stages. This study focused on the examination of the temporal and spatial expression of type XII collagen during experimental PDL remodeling in the rat. The temporal expressions of types I and XII collagen mRNAs were examined by RNA transfer blot and RNase protection assays, respectively, and were found to be relatively stable in the control group throughout the experimental period. In the tooth movement group, the expression of type I collagen increased at 72 hours and sustained the high level of expression at one week, while an increase in the expression of type XII collagen was first noted at the one-week period. The temporal activation of types I and XII collagen expression in the remodeling occurred in a pattern similar to that found during the development of the PDL. The spatial expression of type XII collagen mRNA was examined by in situ hybridization in the one-week tooth-movement specimens. Labeled cells, which were more evident in the tension side, typically exhibited a spindle shape and were surrounded by the mature PDL matrix. Our data suggest that the type XII collagen expression may be closely associated with the functional regeneration of the PDL. PMID- 7876424 TI - Identification of bone-type alkaline phosphatase mRNA from human periodontal ligament cells. AB - Tissue-nonspecific-type alkaline phosphatase is found in the bone, liver, kidney, and other tissues, and its gene consists of 12 exons with the coding sequence beginning in the second exon. Recently, an alternative noncoding first exon was identified in the liver message which differed from that of the previously known osteoblast-derived cDNA sequence. Although these two mRNAs produce an identical protein, they have different promoter regions. The periodontal ligament tissue expresses a high level of alkaline phosphatase activity. To identify its mRNA type, we isolated a full-length cDNA for alkaline phosphatase from a cultured human periodontal ligament cell expression library, using bone-derived tissue nonspecific alkaline phosphatase cDNA as a hybridization probe. The size of this clone was 2.5 kb, and its 5' and 3' untranslated sequences were identical to those of the human tissue-nonspecific type isolated from osteoblastic cells but not to those of the liver type. In addition, the same fragments as in bone derived tissue-nonspecific-type cDNA were detected by the treatment of the cDNA clone with restriction enzymes Hinc II and Pst I. The results suggest that expression of the same alkaline phosphatase isozyme in human periodontal ligament cells may be regulated by the same transcriptional mechanism as in bone. PMID- 7876425 TI - Reduction of infection-stimulated periapical bone resorption by the biological response modifier PGG glucan. AB - Pulpal and periodontal diseases are bacterial infections which result in local connective tissue and bone destruction. Effective host resistance to these infections is primarily mediated by neutrophils and other phagocytic cells. PGG glucan (poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose glucan) is a biological response modifier which stimulates the production of neutrophils and upregulates their phagocytic and bactericidal activity. In the present studies, the effect of PGG glucan on infection-stimulated alveolar bone resorption was tested in an in vivo model. Periapical bone resorption was induced in Sprague-Dawley rats by surgical pulp exposure and subsequent infection from the oral environment. Animals were administered PGG glucan (0.5 mg/kg) or saline (control) subcutaneously the day before and on days 2, 4, 6, 9, 11, 13, 16, and 18 following the pulp exposure procedure. PGG glucan enhanced the number of circulating neutrophils and monocytes and increased neutrophil phagocytic activity approximately two-fold. PGG glucan-treated animals had significantly less infection-stimulated periapical bone resorption than control animals, as determined radiographically (-48.0%; p < 0.001) and by histomorphometry (-40.8% and -42.4% for first and second molars, respectively; p < 0.001). PGG glucan treated animals also had less soft tissue destruction, as indicated by decreased pulpal necrosis. Only 3.3% of the first molar pulps from PGG glucan-treated animals exhibited complete necrosis, as compared with 40.6% of pulps from controls. Finally, PGG glucan had no effect on either PTH- or IL-1-stimulated bone resorption in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876426 TI - Phenytoin at micromolar concentrations is an osteogenic agent for human-mandible derived bone cells in vitro. AB - The present study sought to test the hypothesis that phenytoin acts on normal human-mandible-derived bone cells to induce osteogenic effects. To test the effects of phenytoin on bone cell proliferation, we measured [3H]-thymidine incorporation into cell DNA during the final four hr of a 24-hour incubation with phenytoin. Phenytoin at micromolar concentrations significantly stimulated the [3H]-thymidine incorporation in a dose-dependent, biphasic, manner with a maximal effect at from 10 to 50 microM. We confirmed the proliferative effect of phenytoin by counting cell number. To evaluate the effects of phenytoin on osteoblastic differentiation, we determined alkaline-phosphatase specific activity and found that phenytoin at micromolar concentrations significantly increased that activity in a dose-dependent manner, with maximal stimulation at approximately 1 microM. To investigate the effects of phenytoin on mature osteoblastic activities, we measured de novo collagen synthesis and osteocalcin secretion. Mitogenic doses of phenytoin significantly increased collagen synthesis and osteocalcin secretion in a dose-dependent, biphasic, manner, with the maximal stimulatory dose at from 5 to 10 microM. In summary, phenytoin at micromolar ranges increased (a) [3H]-thymidine incorporation and cell number, (b) alkaline-phosphatase specific activity, (c) collagen synthesis, and (d) osteocalcin secretion in monolayer cultures of normal human-mandible-derived bone cells. These observations are consistent with the premise that low doses of phenytoin act on human craniofacial bone cells to stimulate cell proliferation, differentiation, and mature osteoblastic activities to stimulate bone formation. PMID- 7876427 TI - Phosphorus magnetic resonance spectroscopy of human masseter muscle. AB - Masseter muscle metabolism is poorly understood. 31P Magnetic Resonance Spectroscopy (MRS) provides an opportunity for non-invasive study of muscle metabolism during rest, exercise, and recovery. The aim of this study was to investigate the changes in high-energy phosphates and pH in human masseter muscle associated with exertional pain. Phosphates and pH were measured with 31P Magnetic Resonance at 2.0 Tesla. The bite force was simultaneously measured with a force transducer. Continuous biting at maximum voluntary bite force (MVBF) and two intermittent biting exercises with different duty cycles were performed to pain intolerance. The light intermittent exercise did not produce pain. Brief MVBF requested at the beginning, during, and end of each exercise showed no decay. Qualitatively, changes in phosphates were similar to those reported from comparable limb muscle exercises: increased inorganic phosphate (Pi), decreased phosphocreatine (PCr), and no changes in ATP level. Quantitatively, however, the Pi/PCr ratio did not reach the levels reported in limb muscles during similar exercises. Also, the pH changed very little. Thus, the lack of fatigue was no surprise, since the level of changes in Pi/PCr and pH, reported to be associated with fatigue in limb muscles, was far less in the masseter. Pain development toward the end of the heavy exercises prevented further depletion of metabolites. Thus, the lack of fatigue generally postulated for the masseter muscle may not be due to resistance to fatigue of these fibers, but rather to the presence of pain preventing the fatigue. However, no specific metabolic changes associated with exertional pain were found. PMID- 7876428 TI - Characterization of low-molecular-weight peptides in human parotid saliva. AB - The low-molecular-weight components of human saliva remain poorly characterized. Therefore, low-molecular-weight peptides (Mr < 3000) have been purified from human parotid saliva and characterized with respect to their amino acid sequence. From the sequences obtained, it is likely that these peptides are derived from proteolysis of the hydroxyapatite-interactive human salivary proteins, histatins, proline-rich proteins, and statherins. Since human parotid saliva is an amicrobial fluid, much of the low-molecular-weight peptide fraction of this secretion appears to be derived from the proteolytic processing of the larger proteins. Because of their small size, these peptides are likely to be in exchange with dental plaque fluid and may therefore help modulate events such as demineralization/remineralization, microbial attachment, and dental plaque metabolism at the tooth-saliva interface. PMID- 7876429 TI - Binding of human high-molecular-weight salivary mucins (MG1) to Hemophilus parainfluenzae. AB - In human saliva, two different mucin populations can be distinguished, viz., high molecular-weight mucins (MG1, mol. wt > 1 x 10(6)) and low-molecular-weight mucins (MG2, mol. wt approximately 125 kD). The carbohydrate moiety of MG1 displays a wide spectrum of oligosaccharide structures, varying in composition, length, branching, and acidity. The biological significance of the heterogeneity in carbohydrate structures of mucins is unclear. The present investigation focused on the question whether MG1, because of its diverse carbohydrate side chain population, can bind to a large variety of oral micro-organisms. A replica plate technique, in combination with immunochemical detection with monoclonal antibodies against MG1, was used to screen in vivo human oral microflora for the presence of micro-organisms which could bind the high-molecular-weight salivary mucin MG1. Binding to purified MG1 was established for Hemophilus (para)influenzae species, whereas other species, including Streptococcus and Staphylococcus, were negative. MG1 binding to Hemophilus parainfluenzae could be abolished by protease treatment of MG1. In contrast, periodate acid treatment, partial deglycosylation, or addition of monosaccharides did not affect MG1 binding to H. parainfluenzae, indicating that MG1 carbohydrate side-chains were not directly involved in the binding. The binding was pH-dependent, showing an increase when the pH was lowered from 8.0 to 4.0. These data indicate that MG1 can be bound in a selective manner by Hemophilus spp. and suggest that the 'naked' unglycosylated polypeptide moiety of MG1 is involved in its binding to Hemophilus parainfluenzae. PMID- 7876430 TI - Effect of aging on animal response to chronic fluoride exposure. AB - This study was conducted to test the hypothesis that physiological changes which occur during aging increase the biological impact of fluoride and reduce the threshold of safe fluoride exposure. Four groups of rats were fed a low-fluoride diet (< 1.2 ppm) ad libitum and received 0, 5, 15, or 50 ppm fluoride in their drinking water. Animals were killed after three, six, 12, or 18 months of treatment. Blood and urine were monitored for biochemical markers of tissue function, and plasma, urine, feces, and representative tissues were analyzed for fluoride. In addition, bone marrow cells from animals killed after 18 months of treatment were examined for frequency of sister chromatid exchange (SCE), a marker of genetic damage. Study results indicated that, within treatment groups, fluoride intake, excretion, and retention did not change significantly between three and 18 months. Fluoride concentration in soft tissues did not change with treatment duration in the fluoride-treated animals. Mineralized tissue fluoride concentration and the total fluoride in the carcasses increased continually as the animals aged. In spite of significant, dose-related differences in tissue fluoride levels which occurred in all age groups in this study, there were no indications that increased fluoride in the tissues caused any adverse physiological or genotoxic effects. None of the monitored clinical "wellness" markers of tissue integrity and function was altered by fluoride in a clinically significant manner. Therefore, there was no evidence from this study that aging reduces the threshold of safe chronic fluoride exposure. PMID- 7876431 TI - Effect of hydrostatic pressure on the diffusion of monomers through dentin in vitro. AB - In previous work, the diffusion of monomers from composite and bonding resins through dentin was demonstrated in vitro. The monomers triethylene glycol dimethacrylate (TEGDMA) and 2-hydroxyethyl methacrylate (HEMA) were identified in samples from the pulp space. In the current study, we examined the effects of two levels of positive hydrostatic pressure on the passage of resin monomers through dentin in vitro from a composite-resin/bonding-resin combination to test the hypothesis that monomer diffusion is prevented by such pressure. An occlusal cavity prepared in the tooth crown was restored with the resins. Distilled water samples from the pulpal space were removed over time and analyzed for monomer content by high-performance liquid chromatography and mass spectrometry. Positive pulpal pressure reduced but did not prevent pulpward movement of diluent monomers that leach from bonding agents and from resin composites through dentin in vitro. The degree of reduction of diffusion was greater with TEGDMA than with the lower molecular-weight monomer HEMA. PMID- 7876432 TI - Tooth color and reflectance as related to light scattering and enamel hardness. AB - Tooth color is determined by the paths of light inside the tooth and absorption along these paths. This paper tests the hypothesis that, since the paths are determined by scattering, a relation between color and scattering coefficients exists. One hundred and two extracted incisors were fixed in formalin, mounted in a standardized position in brass holders, and pumiced. A facet was prepared near the incisal edge on the labial plane to allow for Knoop hardness measurements with a 500-gram load. Light scattering by the enamel was measured in a 45 degrees/0 degrees geometry; light scattering by both enamel and dentin was measured in a 0 degrees/0 degrees geometry. The reflection spectrum of the tooth was measured from the labial plane with a spectroradiometer in a 45 degrees/0 degrees geometry, with standard illuminant A and standard illuminant D65. To include all volume-reflected light, we used entire-tooth illumination and small area measurement. CIELAB color coordinates were calculated from the spectra. Neither spectra nor coordinates showed evidence of a contribution of fluorescence to tooth color. Averaged values and standard deviations for L*,a*,b* were 69.9 (4.1), 1.22 (1.4), and 17.9 (2.9), respectively. Both scattering coefficients averaged to 0.6 (0.4) mm-1; Knoop hardness number was, on average, 271 (39) kg/mm2. L* correlated with a* (r = -0.51), with the enamel scattering coefficient (r = 0.60), and slightly with hardness (r = 0.17, p = 0.03). The colors of 28 teeth from which the enamel was removed correlated strongly with the colors of the complete tooth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876433 TI - Effects of treatment and storage conditions on ceramic/composite bond strength. AB - During the past few years, the interest in using ceramic inlays and veneers has increased. New materials and methods have been introduced to bond these restorations to resinous materials. Since our knowledge of how to optimize such bonding is limited, the objective of this study was to test the hypothesis that various surface treatment variables and combinations of these variables affect the strength of the ceramic/composite interphase of ceramic inlays differently. The influences of material composition, surface-roughening method, silane treatment, silane heat treatment, and storage condition on bond strength were investigated. Three ceramics (Dicor, Mirage, Vitabloc), three surface-roughening methods (etching, sandblasting, grinding), three silane treatments (gamma methacryloxypropyltrimethoxysilane [MPS], MPS+paratoluidine, vinyltrichlorosilane), two heat treatments (20 degrees C for 60 s, 100 degrees C for 60 s), and two storage conditions (24-hour dry, one yr in water at 37 degrees C) were studied. For each of the 108 combinations, five specimens were tested. Ceramic cylinders were treated according to group assignment and bonded to blocks of the same ceramic material with a dual-cured resin. The shear bond strength was determined, and the experimental factors were evaluated by analysis of variance. The results showed that surface-roughening method had the strongest effect on bond strength, while ceramic selection had the least significant effect. Of the surface-roughening methods, etching was associated with higher bond strength values than either sandblasting or grinding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876434 TI - Force threshold for hearing by direct bone conduction. AB - The bone-anchored hearing aid is connected, by means of a skin-penetrating bayonet coupling, to an implanted titanium fixture. Hence, direct bone conduction (dbc) excitation is used. Since no international standard of audiometric zero for dbc force threshold exists, it is of general interest to determine the dbc force threshold for normal hearing subjects. Two different methods have previously been applied to estimate the relation between bone conduction (bc) and dbc thresholds. One preliminary problem was to make a measurement of the output-force level of dbc transducers, which is equivalent to the situation in situ. A skull simulator, TU-1000, has been designed for measuring the output-force level of dbc transducers. The skull simulator does, in an adequate way, reflect the mechanical point impedance of the human skull. This opportunity to determine equivalent dbc force thresholds has motivated the present study in which a linear relation between the dbc force threshold and the bc force threshold was estimated. The estimate found in the present study conforms fairly well with the two previously found estimates. It is suggested that the estimate found in the present study be used as the reference equivalent threshold force level for dbc. PMID- 7876435 TI - Contralateral and ipsilateral suppression of the 2f1-f2 distortion product in human subjects. AB - The amplitude of the 2f1-f2 distortion product was measured under four conditions in human subjects: during simple two-tone stimulation, during stimulation with a third, pure tone in the ipsilateral ear, during contralateral stimulation with broadband noise, and with combined ipsilateral third tone and contralateral noise. The amount of ipsilateral suppression produced varied with suppressor frequency but was maximum close to the f2 primary frequency as previously demonstrated using similar stimulus parameters [A. M. Brown and D. T. Kemp, Hear. Res. 13, 29-37 (1984); F. P. Harris, R. Probst, and L. Xu, ibid. 64, 133-141 (1992)]. Contralateral stimulation also suppressed the level of distortion. During ipsilateral suppression combined with contralateral stimulation, the amount of ipsilateral suppression of the distortion product was reduced. This interaction may indicate a common mechanism for ipsilateral and contralateral suppression. The decrease in ipsilateral suppression under contralateral stimulation was most pronounced at the peak of the ipsilateral suppression tuning curves and this produced some broadening of the function. In the majority of ipsilateral suppression curves, the peak ipsilateral suppression frequency was observed to shift upwards during contralateral stimulation. These results suggest that contralateral stimulation alters the frequency-selective properties of the cochlear response. PMID- 7876436 TI - Intensity discrimination under forward and backward masking: role of referential coding. AB - The present experiments investigated the hypothesis that listeners can code intensity by reference to proximal stimuli in order to improve intensity discrimination performance in conditions of nonsimultaneous masking. The experiments used 30-ms tone bursts as the masker, pedestal, and "proximal burst." The masker level was 80 dB, the pedestal level was 50 dB. In the first experiment the silent interval between the masker and the pedestal was varied. Surprisingly, in both forward and backward masking situations, the Weber fraction decreased as the silent interval was decreased from 100 to 12.5 ms. This is consistent with the referential coding hypothesis: At short intervals performance improves because the level of the pedestal is coded by reference to the proximal masker. In a further set of experiments, the silent interval was 100 ms and an additional proximal burst was presented either 12.5 ms before or 12.5 ms after the pedestal. The proximal burst produced a substantial decrease in the Weber fraction, but only when it was close in frequency to the pedestal, and with a higher intensity. The results are consistent with the auditory system having the ability to produce a robust intensity measure by reference to proximal signals. These findings also provide further evidence that the mid-level elevation in forward masking is not solely the result of processes operating at the level of the auditory nerve. PMID- 7876437 TI - Recovery of thresholds and temporal integration in adult chickens after high level 525-Hz pure-tone exposure. AB - Three adult, female chickens, previously trained to detect pure tones using a positive reinforcement paradigm, were exposed to pure tones at 525 Hz at 120-dB sound-pressure level for 48 h. Immediately after exposure, pure-tone thresholds were elevated between 10 and 56 dB compared to pre-exposure values. The configuration of the initial hearing loss was essentially flat between 500 and 2000 Hz, with slightly less loss at lower and higher frequencies. Over the course of 100 to 600 h, depending on subject and test frequency, thresholds returned to preexposure levels. The slopes of the threshold-duration functions measured shortly after exposure were shallower than normal, but returned to the normal slope of approximately 3 dB per doubling of duration as hearing loss resolved to less than 15 to 20 dB. The cochleas from additional chickens examined by scanning electron microscopy (SEM) and fluorescence microscopy between 0 and 1512 h post exposure showed extensive damage to the tectorial membrane over the middle two thirds of the cochlea, with mild to moderate hair cell loss in the region of the cochlea associated with the exposure frequency. PMID- 7876439 TI - Comparison of auditory filter shapes obtained with notched-noise and noise-tone maskers. AB - The notched-noise method has been widely used to estimate the shape of the auditory filter. Results obtained using this method may be influenced by combination bands produced by the interaction of components within the upper band of noise in the notched-noise masker. To assess the possible effect of such combination bands, results were compared for two types of masker: A notched noise, as used in previous experiments; and a masker in which the upper band of noise was replaced by a sinusoid with a frequency corresponding to the lower edge frequency of that band. This is referred to as the noise-tone masker. The signal frequency was 2 kHz, and measurements were obtained for two different spectrum levels of the noise masker, 30 and 45 dB. Auditory filter shapes derived using the two maskers were similar on their low-frequency sides, as expected. The low frequency sides were less steep at the higher masker level. The high-frequency sides of the auditory filters derived using the noise-tone masker were sometimes slightly steeper than those obtained using the notched-noise masker, but the effect was generally small. Changes with level on the high-frequency sides were not consistent across subjects. An analysis of the notched-noise data taking into account the effects of the combination bands suggests that the maximal spectrum level of the combination bands, in the region just below the lower spectral edge of the primary noise band, is about 20 to 30 dB below the spectrum level of the primary band.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876438 TI - Frequency selectivity and consonant recognition for hearing-impaired and normal hearing listeners with equivalent masked thresholds. AB - Thresholds in notched-noise maskers (NN) and narrow-band maskers (NB) were measured for normal-hearing and hearing-impaired subject pairs who were listening in a background of spectrally shaped broadband noise (SSBB). Consonant recognition was also measured in SSBB. SSBB was adjusted so that thresholds in that noise for each normal-hearing/hearing-impaired subject pair were equal. Threshold and signal-level differences between subject pairs were minimized with the addition of threshold-elevating SSBB, and the presence of a noise background for both groups provided a comparable listening environment for all subjects. At signal frequencies outside masker passbands, thresholds in NN and NB for hearing impaired subjects were higher than for normal-hearing subjects, although threshold differences were much smaller than observed between normal-hearing and hearing-impaired subjects without SSBB. No consistent differences in consonant recognition measured in SSBB were observed between groups. The pattern of results is comparable to that observed in a previous experiment [Dubno and Schaefer, J. Acoust. Soc. Am. 91, 2110-2121 (1992)] in which thresholds in NN and NB, and consonant recognition, for hearing-impaired listeners were compared to results obtained for normal-hearing subjects, but only normal-hearing subjects listened in SSBB. Using a modified power-law model of masking additivity, thresholds in combined-masker conditions were estimated. Masking effects for spectrally overlapping maskers were similar for normal-hearing and hearing-impaired listeners and suggest that residual differences between subject groups are not due to the presence of an additional background noise. PMID- 7876440 TI - Changes in intensity discrimination following monaural long-term use of a hearing aid. AB - Previous work has shown that a normally aided ear tested without the hearing aid is better able to identify speech-in-noise than the unaided ear at high sound levels, while performance for the unaided ear is superior at lower sound levels [S. Gatehouse, J. Acoust. Soc. Am. 86, 2103-6 (1989); J. Acoust. Soc. Am. 92, 1258-68 (1992)]. This effect was further explored using intensity discrimination for complex stimuli. Stimuli were half-octave bandpass-filtered tone complexes centered at 0.25 and 3 kHz. Four bilateral, symmetric hearing-impaired listeners with mean HL of 24 dB at 0.25 kHz, and 58 dB at 3 kHz were tested. Intensity discrimination was performed across the dynamic range of the listeners. At sound pressure levels greater than 85 dB, the normally aided ear tested without the aid was more sensitive to changes in intensity than the unaided ear, whereas at lower levels, the converse occurred. This pattern was observed only for the 3-kHz center frequency, and not for the 0.25-kHz center frequency. Insertion gain measurements using the aids at normal volume showed an average of 20 dB gain at 3 kHz, and -2 dB gain at 0.25 kHz. The changes in intensity discrimination in the normally aided ear are consistent with the frequency-gain characteristics of the hearing aid, and suggest that a change in intensity coding occurred. PMID- 7876441 TI - The effect of multichannel dynamic compression on speech intelligibility. AB - In the recent literature on dynamic compression in hearing aids, a controversial discussion about the benefit of multichannel compression with short time constants has been raised. In this paper, some experimental results are contributed to the discussion: For low signal-to-noise ratios, a detrimental effect of fast multichannel compression on speech intelligibility in normal hearing listeners is found. However, a distinct degradation in speech quality and virtually no decrease in speech intelligibility is observed for comparatively high signal-to-noise ratios and compression ratios of up to 3. Since the predictions of the Speech Transmission Index deviate substantially from these results, its applications as an objective measure of intelligibility may not be extended to compressed speech. PMID- 7876442 TI - Gender differences in a longitudinal study of age-associated hearing loss. AB - Current studies are inconclusive regarding specific patterns of gender differences in age-associated hearing loss. This paper presents results from the largest and longest longitudinal study reported to date of changes in pure-tone hearing thresholds in men and women screened for otological disorders and noise induced hearing loss. Since 1965, the Baltimore Longitudinal Study of Aging has collected hearing thresholds from 500 to 8000 Hz using a pulsed-tone tracking procedure. Mixed-effects regression models were used to estimate longitudinal patterns of change in hearing thresholds in 681 men and 416 women with no evidence of otological disease, unilateral hearing loss, or noise-induced hearing loss. The results show (1) hearing sensitivity declines more than twice as fast in men as in women at most ages and frequencies, (2) longitudinal declines in hearing sensitivity are detectable at all frequencies among men by age 30, but the age of onset of decline is later in women at most frequencies and varies by frequency in women, (3) women have more sensitive hearing than men at frequencies above 1000 Hz but men have more sensitive hearing than women at lower frequencies, (4) learning effects bias cross-sectional and short-term longitudinal studies, and (5) hearing levels and longitudinal patterns of change are highly variable, even in this highly selected group. These longitudinal findings document gender differences in hearing levels and show that age associated hearing loss occurs even in a group with relatively low-noise occupations and with no evidence of noise-induced hearing loss. PMID- 7876443 TI - Multichannel compression hearing aids: effect of number of channels on speech discrimination in noise. AB - Full-range multichannel compression hearing aids (MCCHAs) with 4, 6, 8, 12, and 16 independent frequency channels were used to determine the effect of the number of channels on the speech discrimination of mild to moderately severe hearing impaired subjects. Signal-to-noise ratios (S/Ns) from -5 to 15 dB with speech spectrum noise (70 dB SPL) and two voices (male and female) were used. Average speech discrimination for 16 hearing-impaired subjects increased from 4 to 8 channels but did not change significantly between 8 and 16 channels. The effect of the number of channels did not vary significantly with S/N. Analyses of speech discrimination performance within phonemic categories as well as consonant confusion analyses revealed response shifts with the number of channels that were consistent with increasing transmission of useful high-frequency speech information as the number of channels increased. These results indicate that a MCCHA with at least 8 (and up to 16) channels provides the mild to moderately severe hearing-impaired subjects with acoustic information that facilitates speech discrimination in speech-band noise. PMID- 7876444 TI - Enhanced speech perception at low signal-to-noise ratios with multichannel compression hearing aids. AB - The effect of the signal-to-noise ratio (S/N) on speech discrimination was measured for two types of hearing-aid amplification, (1) full-range multichannel compression with eight independent frequency bands and (2) frequency-equalized linear amplification. Signal-to-noise ratios from -5 to 15 dB with speech spectrum noise (at 70 dB SPL) and two voices (male and female) were used. The effect of S/N differed for the two aid types: As the S/N decreased, speech discrimination became relatively better with the multichannel compression hearing aid (MCCHA) in comparison to the linear amplification hearing aid (LAHA). Furthermore, this shift in MCCHA-LAHA performance occurred for every subject, independent of which aid produced better overall performance. Of 16 hearing impaired subjects, 7 showed significantly better overall speech discrimination with the MCCHA than with the LAHA, 5 showed no difference, and 4 showed significantly better discrimination with the LAHA. Hearing-loss severity and MCCHA performance also were related: Subjects with less severe impairments showed greater improvement with the MCCHA. In a normal-hearing listener, the speech discrimination deficit produced by these MCCHAs was small and not statistically significant in most cases. Taken together, these results indicate that a full range eight-channel MCCHA, for a mild to moderately severe hearing loss, causes little information degradation and can be of great benefit for speech discrimination in noise, particularly at low S/N. PMID- 7876445 TI - Pulsatile airflow during phonation: an excised larynx model. AB - Pulsatile airflow in the excised larynx was investigated with simultaneous recordings of air velocity, subglottal pressure, volume flow, and the electroglottograph signal for various conditions of the larynx. Canine larynges were mounted on a bench with sutures attached to cartilages to mimic the function of laryngeal muscles. Sustained oscillations were established and maintained with the flow of heated and humidified air through the trachea. The instantaneous air velocity above the glottis, which is the summation of a periodic velocity and the turbulent component, was measured with a constant temperature hot-wire probe at various locations. The phase-averaged velocity was used to construct the patterns of jet flow at selected time frames of the oscillation cycle. Results suggest that supraglottal air velocity is highly spatially and temporally dependent. Cycles of local air velocity with double peaks were not uncommon and a case is provided. For one phase-averaged phonatory cycle, a 9 x 13 velocity measurement grid demonstrated strongly nonuniform velocity surfaces for eight phases of the cycle, with greater velocities located anteriorly. PMID- 7876446 TI - Voice simulation with a body-cover model of the vocal folds. AB - A simple, low-dimensional model of the body-cover vocal-fold structure is proposed as a research tool to study both normal and pathological vocal-fold vibration. It maintains the simplicity of a two-mass model but allows for physiologically relevant adjustments and separate vibration of the body and the cover. The classic two-mass model of the vocal folds [K. Ishizaka and J. L. Flanagan, Bell Syst. Tech. J. 51, 1233-1268 (1972)] has been extended to a three mass model in order to more realistically represent the body-cover vocal-fold structure [M. Hirano, Folia Phoniar. 26, 89-94 (1974)]. The model consists of two "cover" masses coupled laterally to a "body" mass by nonlinear springs and viscous damping elements. The body mass, which represents muscle tissue, is further coupled laterally to a rigid wall (assumed to represent the thyroid cartilage) by a nonlinear spring and a damping element. The two cover springs are intended to represent the elastic properties of the epithelium and the lamina propria while the body spring simulates the tension produced by contraction of the thyroarytenoid muscle. Thus contractions of the cricothyroid and thyroarytenoid muscles are incorporated in the values used for the stiffness parameters of the body and cover springs. Additionally, the two cover masses are coupled to each other through a linear spring which can represent vertical mucosal wave propagation. Simulations show reasonable similarity to observed vocal-fold motion, measured vertical phase difference, and mucosal wave velocity, as well as experimentally obtained intraglottal pressure. PMID- 7876447 TI - Integrality of nasalization and F1 in vowels in isolation and before oral and nasal consonants: a detection-theoretic application of the Garner paradigm. AB - In vowel height contrasts, tongue height and soft palate height covary. A series of vowel classification experiments examined the perceptual interactions between F1 and nasalization, the principal acoustic correlates of these articulations. Listeners classified imperfectly discriminable stimuli in the set of tasks that compose the Garner paradigm. Detection-theoretic models applied to the data led to the conclusion that vowels, whether in isolation, before oral consonants, or before nasal consonants, display integrality of F1 and nasalization. The contrary conclusion reached by Krakow et al. [J. Acoust. Soc. Am. 83, 1146-1158 (1988)] on the basis of data from a trading relations experiment reflect a limitation of that design for studying perceptual interaction. A second experiment used an array "rotated" in the stimulus space to determine whether F1 and nasalization are privileged, perceptually primary dimensions. A new method for predicting classification performance for the rotated array without the assumption of primacy showed that they are not. PMID- 7876448 TI - Linguistic influences in adult perception of non-native vowel contrasts. AB - Perception of natural productions of two German vowels contrasts, /y/ vs /u/ and /Y/ vs /U/, was examined in monolingual English-speaking adults. Subjects were tested on multiple exemplars of the contrasting vowels produced in a dVt syllable by a native German speaker. Discrimination accuracy in an AXB discrimination task was well above chance for both contrasts. Most of the English adults failed to attain "nativelike" discrimination accuracy for the lax vowel pair /U/ vs /Y/, whereas all subjects showed nativelike performance in discriminating the tense vowel pair /u/ vs /y/. Results of a keyword identification and rating task provided evidence that English listeners' mapping of the German vowel to English vowel categories can be characterized as a category goodness difference assimilation, and that the difference in category goodness was more pronounced for the tense vowel pair than for the lax vowel pair. The results failed to support the hypothesis that the acoustic structure of vowels consistently favors auditory coding. Overall, the findings are compatible with existing data on discrimination of cross-language consonant contrasts in natural speech and suggest that linguistic experience shapes the discrimination of vowels and consonants as phonetic segmental units in similar ways. PMID- 7876449 TI - Wave collation visual speech display: design and evaluation. AB - The wave collation display is a pitch-synchronous, time-domain visual speech display. Collation processing maps the speech waveform into a planar array, condensing the waveform and making speech information, including pitch contour and formant transitions, salient. Evaluation included both analytic evaluation and training. Analytic evaluation was based on a perceptual sorting task using untrained subjects. Subjects sorted printed speech display tokens by visual similarity in a match-to-exemplar design. Stimuli included vowels, with single speaker, multiple speakers, and multiple phonemic contexts, and voiceless consonants. Results for untrained subjects ranged from 73% correct (consonants) and 71% correct (vowels) for single speaker tokens to 46% correct (multiple speaker vowels). For comparison, analytic evaluation using spectrograms was also performed for vowels with single and multiple speakers. Overall results were statistically equivalent to the collation display, with 76% correct (single speaker vowels) and 44% correct (multiple speakers). In the training component, four subjects were trained on collation display sorting tasks as above; after mastering these tasks, generalization to novel stimuli was tested. The tasks were mastered in a few hours, and generalization to novel tokens from a familiar speaker was nearly perfect; generalization to unfamiliar speakers was imperfect. PMID- 7876450 TI - Comparison of the anisotropy of apparent integrated ultrasonic backscatter from fixed human tendon and fixed human myocardium. AB - The content and organization of collagen in the cardiac interstitium may represent significant determinants of the ultrasonic scattering properties of myocardium. This study was designed to investigate the anisotropic backscattering properties of a fibrous soft tissue exhibiting an ordered arrangement of fibers similar to myocardium, but possessing a substantially greater content of collagen. Human Achilles tendon was chosen for this study because it possesses a simple unidirectional arrangement of fibers and a high content of collagen compared to normal myocardium. Integrated (frequency-averaged) backscatter was measured from ten formalin fixed samples of tendon as a function of insonifying angle relative to the fiber axis of the tissue. The samples were insonified in a water bath using a 5-MHz center frequency piezoelectric transducer. Maximum backscatter occurred for insonification perpendicular to the fibers, and minimum backscatter occurred for insonification parallel to the fibers. The mean peak to nadir variation, or magnitude of anisotropy, of integrated backscatter for the ten formalin fixed samples of tendon was 36.3 dB. This compares to 14.5 dB for formalin fixed human myocardium measured in an earlier study by our laboratory. PMID- 7876451 TI - Proportional duration and proportional variance as factors in auditory pattern discrimination. PMID- 7876452 TI - Further comments on proportional duration and proportional variance as factors in auditory pattern discrimination. PMID- 7876453 TI - A formant bandwidth estimation procedure for vowel synthesis [43.72.Ja]. AB - The specification of vowel formant bandwidths for speech synthesis has been inconsistent in the past, perhaps due to the difficulty of measuring formant bandwidths in natural speech and the possible perceptual insignificance of formant bandwidths on the intelligibility of synthetic speech. Here, regression equations are presented for the estimation of formant bandwidths based on measurements from natural speech which is based only on formant center frequency and independent of other formant values. Current usage, as well as comparison with another well-known estimation algorithm suggests that the new procedure should be quite acceptable for some types of speech synthesis. PMID- 7876454 TI - Gender-related assessment of childhood play. AB - Parent-report based scales for the assessment of sex-dimorphic behavior are an important tool in research on psychosexual differentiation and its disorders. This paper presents the factor analysis and corresponding scale development for the slightly expanded Child Game Participation Questionnaire (Bates & Bentler, 1973), based on the parents of a demographically diverse school sample of 355 girls and 333 boys aged 6 to 10 years. Evidence supporting each of three theoretical positions in gender assessment--unidimensional bipolar, two dimensional unipolar, and multidimensional--was provided. Effect sizes were unusually large for gender, but small for age, socioeconomic level, and race/ethnicity. PMID- 7876455 TI - Children's emotional and physiological responses to interadult angry behavior: the role of history of interparental hostility. AB - Relations between history of marital discord and responses to interadult angry behavior were examined in preschoolers. Children watched/listened to an angry interaction between two adults, while their heart rate (HR) and skin conductance response (SCR) and skin conductance level (SCL) were monitored; then they were interviewed about their emotional responses to the argument. Children were also videotaped during the session and their overt behavioral distress responses were coded. In comparison to children from low-conflict homes, children from high conflict homes (a) exhibited more overt behavioral distress in response to the argument, and (b) perceived the angry interaction as less negative in affect. Children's HR reactivity to the angry interaction was influenced by both marital conflict and the gender of the subject. In comparison to girls from low-conflict homes, those from high-conflict homes exhibited more HR reactivity to the argument. For boys, physical violence in the home was negatively associated with HR reactivity. PMID- 7876456 TI - Interrater reliability of the DSM-III-R with preschool children. AB - Little attention has been paid to evaluating the use of DSM-III-R with preschool children. Children (N = 510) ages 2 to 5 years who were screened at the time of a pediatric visit were selected to participate in an evaluation which included questionnaires, a semistructured interview, developmental testing, and a play observation. Following the evaluation, two clinical child psychologists independently assigned DSM-III-R diagnoses. For each diagnostic category, kappa and Y coefficients were calculated; Y coefficients are less sensitive to base rates of disorders. For overall agreement, the weighted mean kappa (.61), and mean Y (.66) were moderately high. Overall agreement that the child had at least one of the disruptive disorders was substantial (kappa = .64; Y = .65); agreement that there was at least one of the emotional disorders was moderate for kappa (.54), but substantial for Y (.70). Kappa coefficients were higher for major categories of disorder than for specific disorders; however, Y coefficients did not show a decline for specific disorders. Interrater reliability of DSM-III-R appears to be similar for preschoolers and older children. PMID- 7876457 TI - The mediating role of anxiety in self-reported somatic complaints of depressed adolescents. AB - This study examined the mediating role of anxiety in the self-reports of somatic complaints in 96 depressed adolescent inpatients. Sixty-four subjects with major depressive episodes and comorbid anxiety disorders (MDE-A) determined from the Diagnostic Interview for Children and Adolescents--Revised (DICA-R) reported significantly more somatic complaints than 32 adolescents having major depressive episodes without comorbid anxiety (MDE). An analysis of covariance demonstrated that, with anxiety symptoms controlled, MDE and MDE-A groups did not differ significantly in somatic complaints. A hierarchical multiple-regression analysis revealed that, with demographic and anxiety symptoms controlled, depressive symptoms did not contribute to the explanation or prediction of somatic complaints. The results suggest that anxious, but not depressive symptoms, are independently associated with somatic complaints. The results are discussed in light of new affective models of psychopathology. PMID- 7876459 TI - Adolescents', parents', and teachers' distress over adolescents' behavior. AB - This study evaluated adolescents', parents', and teachers' self-reported distress and wishes to change adolescents' emotional/behavioral problems in a sample of clinically referred adolescents. Parents reported being bothered more than adolescents or teachers by adolescents' internalizing behavior. Both parents and teachers rated adolescents' externalizing behavior as more bothersome than did adolescents. Adolescents were significantly less likely to want to change their behavior than were parents or teachers. In addition, adolescents were significantly more likely to want to change their internalizing problems than their externalizing problems. For all three informants, being bothered by adolescents' behaviors was strongly associated with a desire to change the behaviors. Clinical implications of these findings are discussed. PMID- 7876458 TI - Psychometric properties of parents and children as informants in child psychiatry epidemiology with the Spanish Diagnostic Interview Schedule for Children (DISC.2). AB - Parent and child reports were examined to study how epidemiological researchers can best use the information provided to describe childhood psychopathology. As part of a multisite methodologic study of mental disorders in children, a probability sample (N = 248) of children aged 9 to 17 years from the San Juan metropolitan area was selected. This sample was enriched with 74 clinic cases. Both parents and children were administered the DISC.2. Results showed that prevalence estimates were influenced by the informant. The clinicians' diagnosis is more concordant with children's reports of depression and with parents' reports of disruptive disorders. Parents and children provided unique information when interviewed with a structured psychiatric interview about child psychopathology. Their unique perspectives contributed to the observed discordance that emerged when DISC parent and DISC child results are compared. Combining the two perspectives with a simple "OR" rule at the symptom level did not seem to capture the unique perspectives. PMID- 7876460 TI - Silica induced suppression of the production of third and fifth components of the complement system by human lung cells in vitro. AB - Although investigations to date have demonstrated the ability of the monocyte/macrophage to synthesize complement components, only a limited number of studies on complement synthesis by nonhepatic tissue cells have been reported. To begin to fill this gap in our knowledge we have recently evaluated the ability of lung tissue cells to synthesize and secrete various complement components in vitro. Using 35S-methionine incorporation and immunoprecipitation techniques we have previously demonstrated the ability human lung type II pneumocytes (A549) and human lung fibroblasts (WI-38), to synthesize and secrete a variety of both early and terminal complement components, as well as several regulatory proteins including Clr, Cls, C4, C3, C5, C6, C7, C8, C9, Factor B, Factor H, Factor I and Cls inactivator. Our present studies demonstrate the capability of silica to regulate complement component production by A549 cells, but not complement component production by WI-38 cells. Specifically, using sensitive ELISAs we demonstrated that a non-toxic dose of silica had the capability to suppress the production of both C3 and C5 by A549 pneumocytes by 40-50 percent, but had no effect on C3 or C5 synthesis by WI-38 fibroblasts. Additionally, using 35S methionine incorporation and TCA precipitation techniques, we demonstrated that suppression of C3 and C5 production by silica treated A549 pneumocytes was not a result of suppression of total protein synthesis. These studies demonstrate that silica, which has been implicated in pulmonary diseases, has the capability to regulate local complement production by lung tissue cells in vitro. In vivo, this suppression of complement production by the type II pneumocytes could alter the local tissue reservoir of complement components during infection and pulmonary injury, thus resulting in depressed pulmonary host defense. PMID- 7876461 TI - Induction of apoptosis in mouse thymocytes by cyclosporin A: an in vitro study. AB - The effect of cyclosporin A (CsA) on mouse thymocytes was investigated in vitro. Ultrastructural examination and DNA electrophoresis of 24hr-CsA-treated thymocytes showed chromatin condensation, cellular shrinkage and nuclear fragmentation in oligonucleosomal fragments. DNA labeling of CsA-treated thymocytes with propidium iodide (PI) showed an increase in the number of apoptotic nuclei compared to untreated thymocytes. Furthermore, flow cytometric analysis using monoclonal antibodies (mAbs) specific to particular thymocyte subsets showed that CsA induces a decrease in the relative number of immature double positive (DP) CD4+CD8+ thymocytes in direct proportion to the concentration of CsA. No significant changes were observed in mature single positive (SP) CD4+CD8- and CD8+CD4- cells. Moreover, the cell viability of CsA treated thymocytes was decreased. These results suggest that CsA induces the programmed cell death of thymocytes in vitro. Taken together with our previous study on the in vivo effect of CsA on mouse thymus and thymocytes, the present study confirms that, in addition to its effect on the thymic epithelium, CsA acts directly on thymocytes by inducing their programmed cell death. We postulate that immature DP thymocytes are the most likely targets of CsA. PMID- 7876462 TI - The effect of interferon on activated peripheral blood T lymphocytes in patients with chronic active hepatitis B. AB - The effect of interferon-alpha 2b treatment on activated T lymphocytes -T cells expressing interleukin-2 receptors-(IL-2R) was studied in 18 patients with chronic active hepatitis B. Blood samples were taken before, on the 2nd, 4th and 6th month of treatment. Patients were divided in 3 groups according to their response to therapy (complete, partial, no response). At the end of treatment, IL 2R+ cells were decreased in the group of patients with complete response, unchanged in patients with partial response and increased in patients with no response. These results confirm the immunomodulatory effect of interferon and reflect the effect of treatment in the management of the disease. PMID- 7876463 TI - Adjuvant activity of the cell wall of Bifidobacterium infantis for in vivo immune responses in mice. AB - We examined the adjuvant activity of the Bifidobacterial Cell Wall preparation (WPG) for in vivo immune responses in mice. We studied three classical immune responses, which are thought to be T-cell mediated responses, to evaluate the adjuvant activity of WPG. The delayed type hypersensitivity (DTH) responses of sheep blood red cell (SRBC)-sensitized mice were significantly augmented by WPG, although the enhancement varied with the timing, route and dosage of injection. The adjuvant activity of WPG was also confirmed by using a glutaraldehyde treated and Concanavalin A associated- tumor vaccine (G-Con A tumor vaccine) system. BALB/c mice sensitized with G-Con A tumor vaccine and WPG improved synergistically in survival time and cure rate compared with those given G-Con A vaccine alone. Spleen cells of Meth A tumor-bearing mice induced antitumor neutralizing activity with the growth of tumor but the activity declined and disappeared at the late stage of tumor growth (over 28 days after tumor transplantation). On the other hand, antitumor neutralizing immunity was prolonged for as long as 33 days in mice inoculated with Meth A tumor and WPG. The requirement of a T-cell subpopulation in the spleen cells of tumor plus WPG treated mice was confirmed using anti-Thy 1.2 antiserum + complement to deplete them. The adjuvant activities of the Bifidobacterial cell wall demonstrated by the in vivo immune responses predict that Bifidobacteria may play a role as an immunomodulator in human and animal intestines. PMID- 7876464 TI - Profile of chicken macrophage functions after exposure to catecholamines in vitro. AB - The effects of catecholamines (CA) on various chicken macrophage functions were examined. Macrophage monolayers were exposed to .01, .1, .25, 1, 2, and 5 micrograms/mL of dopamine (DA), norepinephrine (NE) and epinephrine (E) for 1 hr. All CA were toxic for macrophages at 1-5 micrograms dose range resulting in 25 50% cell death. All CA at the .1 and .25 micrograms/mL level increased E. coli and sheep red blood cells (SRBC) phagocytosis by macrophages. The percentage of Fc-receptor positive macrophages increased after CA exposure. Prolonged exposure of macrophages (3 hr) reduced SRBC phagocytosis by DA-treated but not in NE- and E-treated macrophages. However, after 1 hr exposure and 3 hr recovery period, CA induced changes were reversed in all but DA-treated cultures. Apomorphine and metoclopromide blocked DA whereas propranolol blocked NE and E effects suggesting specificity of the observed effects via catecholaminergic receptors on chicken macrophages. Dopamine and NE (.25 micrograms/mL) did not affect but E exposure enhanced LPS-induced tumoricidal factor production. These findings suggest that CA modulate chicken macrophage effector functions. PMID- 7876465 TI - The comparative pulmonary toxicity of beryllium metal and beryllium oxide in cynomolgus monkeys. AB - Inhalation of beryllium (Be) may result in an immune-mediated, chronic granulomatous pulmonary disorder known as chronic beryllium disease (CBD). The physicochemical form of Be may affect the incidence and severity of CBD. We exposed cynomolgus monkeys, by bronchoscopic, intrabronchiolar instillation, to either beryllium oxide (BeO; heat-treated at 500 degrees C) or Be metal at concentrations selected to achieve equimolar concentrations of available Be2+ ions dissolving from the particles. Monkeys underwent bronchoalveolar lavage of the right and left diaphragmatic lobes at 14, 30, 60, 90, and 120 days post exposure (dpe). Monkeys were sacrificed at 80 and 180 dpe for evaluation of histopathological pulmonary changes. Numbers of lymphocytes from lung lobes of Be metal-exposed, but not BeO-exposed, monkeys were increased at 14, 30 and 90 dpe. Lung lymphocytes were increased for BeO exposed monkeys only at 60 dpe. In vitro, Be-specific, lung lymphocyte proliferation occurred at 14, 60, and 90 dpe for lymphocytes from Be metal-exposed lung lobes only. At no time were values from BeO-exposed lung lobes different from values from control lobes. Lung lesions in Be metal-exposed monkeys were characterized by focally intense, interstitial fibrosis, marked Type II cell hyperplasia, and variable lymphocyte infiltration. Some Be-metal-exposed monkeys had discrete immune granulomas consisting of tightly organized lymphocytic cuffs surrounding nodular aggregates of epithelioid macrophages. Lesions were rarely present in BeO-exposed monkeys and were much less severe. These data suggest that Be metal produces more severe pulmonary lesions than does BeO and that these lesions are accompanied by Be-specific immune responses. PMID- 7876466 TI - Dibutyltin dilaurate induced thymic atrophy and modulation of phosphoinositide pathway of cell signalling in thymocytes of rats. AB - A marked dose dependent reduction in thymus weight and its nucleated cell counts with histological alterations was observed in rats exposed to oral dibutyltin dilaurate (DBTL) for 2 weeks at 2, 4, 8 or 16 mg/kg body weight. The incorporation of [3H]-inositol into all the three major phosphoinositides was drastically reduced in thymocytes in a dose dependent manner. Furthermore, the basal and the mitogen (Con A) stimulated [3H]-inositol phosphates generation was diminished significantly in 8 mg DBTL group. However, in vitro incubation of DBTL with thymocytes failed to evoke any change in phosphoinositide hydrolysis. Similarly, a time and dose dependent inhibition in phosphoinositide synthesis with as high as 80% by 10 microM DBTL was exhibited under in vitro conditions. A 130% and 600% enhancement of protein kinase C (PKC) activity in thymocytes was seen in 4 mg and 8 mg DBTL group, respectively. Addition of DBTL to the cell free assay system of thymocytes resulted in a concentration dependent activation of the enzyme activity. A dose dependent increase in intracellular calcium was also evident when DBTL was added to thymocytes under in vitro conditions. These results are of significance and may bear close relationship to the observed thymic atrophy by DBTL. PMID- 7876467 TI - Immunotherapy in chronic brucellosis. Effect of levamisole and interferon; mechanisms of action and clinical value. AB - Thirty two anergic patients with chronic brucellosis treated with a) interferon alpha 2b(group 1), b) levamisole (group 2) and c) conventional therapy(group 3) were studied. The effect of treatment on T lymphocyte blast formation in the presence of PHA, specific cell mediated immunity against brucella antigens, titers of brucella antibodies and clinical symptoms were evaluated .T lymphocyte blast formation was shown to range in normal levels in all patients before treatment compared to 10 normal controls suggesting against a generalized impairment of cell mediated immunity. Titers of brucella antibodies were significantly decreased in group 1, almost significantly in group 2 and were significantly increased in group 3 at the end of treatment. A significant improvement of symptoms as well as production of leukocyte migration inhibition against brucella antigens were noted in both groups 1 and 2, in contrast to group 3. This response to treatment was however greater in group 1. These findings demonstrate that immunotherapy resulted in both clinical and immunological improvement and that interferon seems to be a more promising therapeutic approach of chronic brucellosis. PMID- 7876468 TI - In vitro combined effects of a triazene compound and interferon-beta on natural immunity against lymphoblastoid cells: studies at effector and target cell level. AB - It was shown that Dacarbazine and other triazene compounds render murine leukemias highly immunogenic and susceptible to natural immunity (NI). In addition a pilot clinical study revealed that Dacarbazine can be cytotoxic for bone marrow blasts in patients with acute non-lymphoblastic leukemias through a mechanism that could be, at least in part, of immunological origin. However triazenes depress antigen-dependent responses and NI, whereas interferons, including interferon-beta (IFN), antagonize drug-induced impairment of NI. Therefore the complex interaction between triazenes and IFN on NI effector (i.e. NK) lymphocytes and human target lymphoblastoid cells has been investigated. The results show that: (a) IFN increases NK activity and antagonizes the depressive effects of methyl-triazene-benzoic acid (MTBA, an in vitro active triazene compound) on the NK function; (b) a lymphoblastoid cell line exposed to multiple in vitro treatments with MTBA, shows increased growth rate, augmented chemoresistance to MTBA, and higher susceptibility to NI than parental cells; (c) as expected IFN pretreatment down-regulates the susceptibility of lymphoblastoid cells to NK effectors; (d) however a net "therapeutic gain" was found if the overall influence of MTBA+IFN on target and effector cells is considered. PMID- 7876469 TI - Thalidomide does not perturb CD2, CD4, CD5, CD8, HLA-DR, or HLA-A, B, C molecules in vitro on the membranes of cells with immune potential. AB - Thalidomide dramatically relieves the signs and symptoms of erythema nodosum leprosum (ENL). ENL is an acute inflammatory complication of lepromatous leprosy. The cause(s) of ENL as well as the mechanism of action of thalidomide in arresting ENL are unknowns. It has been suggested that ENL is the consequence of a transient activation of a cell-mediated-immune (CMI) response to Mycobacterium leprae. To initiate a CMI response, an interaction between adhesion and/or signal transducing molecules on T-cells and molecules on antigen presenting cells would occur. An alteration, induced by thalidomide, of one or more of the molecules on T-cells or antigen presenting cells that are essential to maintaining the reactive state of ENL, could explain Thalidomide's ability to attenuate ENL. Thalidomide did not modify: (a) adhesion and/or signal transducing molecules such as CD2, CD4, CD5 and CD8, or (b) molecules that facilitate antigen presentation such as HLA-DR, HLA-A, HLA-B, or HLA-C. PMID- 7876470 TI - Giant cell tumor of the scaphoid: a case report and review of the literature. PMID- 7876471 TI - Tourniquet compression of a Norplant device. PMID- 7876472 TI - Raynaud's phenomenon associated with the use of pneumatically powered surgical instruments. AB - Five patients developed symptoms of Raynaud's phenomenon and upper extremity paresthesias after 7-32 months of exposure to air-powered surgical instruments used for the harvest of bone for bone banks. Results of cold challenge plethysmography, nerve conduction studies, vibrotactile thresholds, and quantitative sensory testing were as follows: all patients had significant reproducible vasospasm with nondetectable finger systolic blood pressure (FSBP = 0) after local digital cooling; nerve conduction abnormalities included delayed median nerve sensory conduction (< 48 m/s) across 5 of 10 wrists; and no ulnar nerve abnormalities were detected. Vibrotactile thresholds were only modestly elevated, an unexpected outcome given the frequently recognized association between vibrotactile tests and nerve conduction studies. These abnormalities occurred with exposures to frequencies previously thought to be too high to be harmful to medical personnel. PMID- 7876473 TI - Proximal row carpectomy in advanced Kienbock's disease. AB - Sixteen patients with advanced Kienbock's disease (Lichtman stage IIIa and IIIb) were treated with proximal row carpectomy. Two patients were lost to follow-up study. The remaining 14 patients were followed for 3 years (range, 1 to 8 years) and all experienced less pain. Wrist motion was improved or unchanged in 12. Grip strength averaged 72% of the unaffected side. All patients returned to their previous jobs. Proximal row carpectomy in this group of patients provided satisfactory results. PMID- 7876474 TI - Clinical results of tension band fixation of avulsion fractures of the hand. AB - We report 100 cases in which a tension-band technique was used to secure fixation of avulsion fractures within the digits. Included are 51 bony mallet fractures that were subluxed or irreducible, 38 displaced bony gamekeeper's fractures of the thumb, 8 fractures of the lateral phalangeal base, and 3 avulsion fractures that involved the base of the dorsal aspect of the middle phalanx. We evaluated results on the basis of clinical and x-ray film criteria. Excellent or satisfactory results were found in all 38 bony gamekeeper's injuries. All but one gamekeeper's fracture healed; the one nonunion was asymptomatic. All eight patients with lateral avulsion fractures had an excellent or satisfactory result on clinical examination. Seven of the eight had an excellent result on x-ray film evaluation; the one malnuion was asymptomatic. Two of the three fractures with dorsal avulsions of the base of the middle phalanx had a satisfactory result on clinical and x-ray film examination; the one poor result was due to the severity of the comminution of the fracture. However, 21 of the 51 bony mallet injuries had a poor result both clinically and radiographically. We noted numerous postoperative complications including dorsal skin breakdown, superficial and deep infection, and secondary displacement of the fragment. Tension-band fixation is an excellent method for treating various avulsion fractures of the hand such as bony gamekeeper's thumb, lateral avlusion injuries, and dorsal avulsions of the middle phalanx. However, the treatment of bony mallet fingers with tension band fixation is less predictable and should be used with caution. PMID- 7876475 TI - Tension wire fixation of avulsion fractures at the thumb metacarpophalangeal joint. AB - Avulsion fractures of the thumb metacarpophalangeal joint require adequate treatment to prevent instability or articular incongruity. Open reduction and internal fixation may be difficult because of the small fracture fragment size. Nine patients underwent acute open reduction and tension wire fixation of displaced or rotated avulsion fractures. Follow-up examination was at approximately 26 months. All fractures healed in anatomic alignment without instability or articular incongruity. Pain, stiffness, and loss of pinch, were subjectively rated as none in six patients and mild in three. The injured thumb demonstrated firm stability in extension and 30 degrees flexion in all patients. Metacarpophalangeal and interphalangeal motion averaged 77% and 97% of the opposite hand respectively. Planar and palmar abduction averaged 96%. Pinch strength in apposition averaged 97% and in opposition 99% of the uninvolved hand. Grip strength was 96% of the contralateral extremity. PMID- 7876476 TI - The use of island and free flaps in crush avulsion and degloving hand injuries. AB - Reconstructive options for early microsurgical tissue and island flap transfer are discussed in 23 patients with extensive avulsion and degloving injuries of the hands and fingers. The patients were divided into three groups (1) degloving thumb injuries; (2) crush avulsions with or without degloving of the palm and fingers; (3) complete degloving injuries of the hand and distal forearm. There were 11 free and 12 island flap transfers. There was partial loss in two flaps with satisfactory esthetic and functional results in these patients. The advantages and indications for the use of distally based radial forearm flap for degloving thumb injuries and pedicled ulnar forearm flap for avulsion of the distal part of the hand are discussed. The use of free transfer of greater omentum in the cases of extensive degloving of the hand is shown. PMID- 7876477 TI - Fractures of the supracondylar process of the humerus. AB - The supracondylar process of the humerus is a relatively rare but well-known anatomic variant that can be associated with other anomalies. While it usually remains clinically silent, the spur can be responsible for a wide spectrum of symptoms. We present 3 patients with fractures of the supracondylar process and review 12 other cases in the literature. The supracondylar process has potential for fracture and important neurovascular sequelae. PMID- 7876478 TI - Anterior dislocation of the proximal fragment of a scaphoid fracture: a case report. PMID- 7876479 TI - Painful unfused separate ossification center of the ulnar styloid: a case report. PMID- 7876480 TI - Late presentation of a ligamentous ulnar collateral ligament injury in a child. PMID- 7876481 TI - Lateral stability of proximal interphalangeal joint replacement. AB - The lateral stability of the cadaver proximal interphalangeal joint was studied with an electromagnetic tracking system before and after implant replacement. Ten middle fingers were retrieved and randomly divided into two groups for joint replacement with either a silicone rubber flexible finger joint implant or a custom surface replacement prosthesis. Each finger was mounted on a fixture that allowed loading of the proximal interphalangeal joint with tension through the flexor, extensor, and intrinsic tendons. For the intact proximal interphalangeal joint under lateral stress, lateral angulation averaged 4 degrees in extension and 8 degrees with the joint in 60 degrees of flexion. Although lateral angulation increased after surface replacement prosthesis implantation when the joint was flexed more than 20 degrees, comparison with the intact joint showed no statistical difference. With the silicone implant, lateral angulation became more pronounced even in the extended position and showed a significant difference when the proximal interphalangeal joint was flexed more than 20 degrees. PMID- 7876482 TI - Acknowledgment of previous work. PMID- 7876483 TI - Carpal tunnel syndrome. PMID- 7876484 TI - Negative ulnar variance is not a risk factor for Kienbock's disease. PMID- 7876485 TI - Electrical studies as a prognostic factor in the surgical treatment of carpal tunnel syndrome. AB - We attempted to determine if a prognostic value could be associated with preoperative electrodiagnostic testing in patients with carpal tunnel syndrome. Three groups of patients were included in the study of 151 workers whose symptoms were thought to be causally related to their jobs. A clinical diagnosis was made without electrical testing in 26 of the 151 patients. Normal electrical test values were present in 50 of the 125 patients tested, and abnormal values were noted in 75 patients. Pinch, power, and static grasp function were recorded monthly. Similar recovery patterns after operation were seen between the groups and within each group. Return to work time correlated well with measured functional recovery to preoperative levels, but some workers returned to their jobs before they had regained full function. Electrodiagnostic test results did not provide significant data for prediction of functional recovery or re employment after carpal tunnel release. PMID- 7876486 TI - Median nerve displacement through the carpal canal. AB - We determined the direct relationships between wrist position and displacement of the median nerve during active contraction of the flexor tendons at the wrist with an intact, transected transverse carpal ligament (TCL). Nine fresh cadavers were mounted in an apparatus to allow variable wrist position. Excursions of the tendons and displacement of the median nerve were measured by tracking markers with a video camera. Each limb was tested at 0 degree, 30 degrees, and 60 degrees of wrist extension before and after release of the TCL. Excursion of the flexor tendons required for full finger flexion ranged from 2.3 to 3.1 cm (mean, 3 cm). Median nerve displacement ranged from 0.9 to 1.4 cm (mean, 1 cm). The relationship between median nerve and flexor tendon excursion was consistently linear. Finger motion alone allows for median nerve displacement after surgery in the carpal tunnel. PMID- 7876488 TI - Bilateral carpal tunnel syndrome in a normal child. PMID- 7876487 TI - Double incision open technique for carpal tunnel release: an alternative to endoscopic release. AB - I prospectively evaluated the results of 30 consecutive patients with bilateral carpal tunnel release using two techniques. The first release was performed with a standard incision while the opposite hand underwent release by a double incision open technique. Postoperatively, subjective complaints of pain, grip strength, pinch strength, and pillar tenderness were evaluated at 1, 2, 4, 6, and 10 weeks. All patients expressed complete relief of preoperative numbness in both hands. The improvement in pinch and grip strength and lack of pillar tenderness in the hands that underwent the double incision open technique closely matched the reported results of endoscopic carpal tunnel release. There were no complications with either technique. PMID- 7876489 TI - Intraneural topography of the ulnar nerve in the cubital tunnel facilitates anterior transposition. AB - The surgical management of cubital tunnel syndrome includes anterior transposition of the ulnar nerve. The success of all transposition procedures is dependent on placement of the nerve anterior to the medial epicondyle without tension. Fifteen cadaveric upper extremities underwent anterior transposition followed by anterior transposition with separation of the most proximal motor branches from the main ulnar nerve for a distance of 1, 2, and 3 cm. Proximal dissection of these motor branches achieved an average gain in distance from the epicondyle of 71%, with an average distance from the epicondyle of 3.6 cm. The intraneural topography of the ulnar nerve was studied in five additional cases. Cross-section analysis of the fascicular anatomy at 333 microns intervals along the length of the nerve with longitudinal reconstructions confirmed a safe dissection plane without interfascicular plexus formation. The most proximal motor branch in the forearm could be traced proximally an average of 6.7. cm within the nerve before interfascicular mingling occurred (range 6.0 to 7.5 cm). Thus, 6.0 cm represented the upper limit of safe proximal dissection in these nerves. Proximal separation may be performed without disruption of interfascicular plexus connections and will facilitate anterior transposition. PMID- 7876490 TI - Intraneural ulnar nerve pressure changes related to operative techniques for cubital tunnel decompression. AB - To evaluate the effect of critical anatomic structures on the ulnar nerve after cubital tunnel decompression, we determined the intraneural ulnar nerve pressure in 50 fresh cadavers after the following surgical procedures: simple decompression, medial epicondylectomy, subcutaneous transposition, and submuscular transposition by the Learmonth and by the musculofascial lengthening technique. Intraneural pressure was measured in 0 degrees, 30 degrees, 60 degrees, and 90 degrees elbow flexion at locations that were proximal, within, and distal to the cubital tunnel. Statistical analysis compared the mean change in intraneural pressure between the "postoperative" and the baseline "preoperative" pressure measurements for the different surgical strategies. While both the simple decompression and the medial epicondylectomy had significantly lower intraneural pressures than the Learmonth or the subcutaneous transposition, each of these four techniques resulted in elevated intraneural pressures. The musculofascial lengthening technique for submuscular transposition was the only surgical strategy that reduced intraneural ulnar pressure at each site of measurement and for all degrees of elbow flexion, this reduction of pressure being significant in comparison with the other surgical techniques. PMID- 7876491 TI - Chronic peripheral nerve pain treated with direct electrical nerve stimulation. AB - Chronic somatic peripheral nerve pain was treated prospectively in 24 nonrandomized patients by a program of direct electrical nerve stimulation. Patients qualified for the program if anesthetic (lidocaine) nerve block of the involved cutaneous zone of the peripheral nerve relieved symptoms and transcutaneous electrical nerve stimulation transiently improved and did not exacerbate somatic pain. Results were judged according to a pain score. Patients noted improved sleep and complete absence of the need for narcotic pain medication. On the basis of subjective and objective criteria, 18 patients had good or excellent results and 6 had implant failures. Of the six patients with failures, three failed the trial period and did not have implantation, and three had no significant pain relief and were judged as treatment failures. Three patients had late equipment failure after initial good results. Most patients had some relief of pain, which increased their quality of life and eliminated the need for narcotic analgesia. Direct electrical nerve stimulation should be considered for somatic peripheral nerve pain that has not been ameliorated with other methods. It will reduce, although not necessarily eliminate, pain and pain behavior in most patients. PMID- 7876492 TI - Arthroscopic portals of the wrist: an anatomic study. AB - Wrist arthroscopy has become an accepted diagnostic technique, and it is starting to be a useful therapeutic tool. Extensor tendons, the radial artery, and dorsal sensory nerve branches are at risk of injury during this procedure; however, understanding periportal anatomy should make wrist arthroscopy safer. Wrist arthroscopic portals were established in 19 fresh cadaver wrists, after which the limbs were dissected and periportal anatomy was described and quantified. The 1 2, 6R, and 6U portals were the most perilous, while the midcarpal, 3-4, 4-5, and distal radioulnar joint portals were relatively safe. Even "safe" portals had occasional adjacent sensory nerve branches and tendons. A safe technique of establishing wrist arthroscopy portals is emphasized. PMID- 7876493 TI - The relevance of ligament tears or perforations in the diagnosis of wrist pain: an arthrographic study. AB - This study was designed to assess the clinical significance of arthrographic abnormalities in the ligaments of a painful wrist. This was accomplished by means of comparison arthrography of the asymptomatic wrist. Fifty-six consecutive patients with unilateral wrist pain underwent selective bilateral arthrography to assess interruptions of continuity of the triangular fibrocartilage, lunotriquetral, and scapholunate ligaments. The prevalence of bilaterally symmetric lesions was high. In patients with ligament defects in the symptomatic wrist, 88% of defects near the radial attachment of the triangular fibrocartilage, 59% of lunotriquetral defects, and 57% of scapholunate defects were bilateral. Furthermore, physical examination was not predictive of specific ligament defects. This study raises questions concerning the relevance of interrupted ligaments in the diagnosis of wrist pain. PMID- 7876494 TI - Anterior wrist ganglion. AB - This study examined the treatment of anterior wrist ganglions by aspiration and injection or surgical excision. Eighty-four patients treated for an anterior wrist ganglion were studied, with an average followup period of 5 years. Initial treatment by aspiration and injection with corticosteroid was performed in 24 patients, with recurrence in 20. A second aspiration and injection was associated with recurrence in all. Of the 72 patients who underwent surgical excision 14 experienced a recurrence of the ganglion. Four patients with a recurrence underwent a second surgical procedure with successful excision in two patients. The origin of the majority of surgically treated ganglions was on the scaphotrapeziotrapezoid joint and radiocarpal joint. Because of a large number of recurrences after nonoperative treatment, surgical excision is recommended as the primary definitive treatment for anterior wrist ganglions Aspiration and injection may provide palliative relief of symptoms. PMID- 7876495 TI - Dorsal wrist ganglion presenting as anterior wrist ganglion. PMID- 7876496 TI - Palmar dermatoglyphics in congenital hand anomalies. AB - A palmar dermatoglyphic study of 392 hands of patients with congenital hand anomalies was performed to evaluate the number of digital triradii, the position of an axial triradius, the incidence of hypothenar patterns, the pattern intensity, and the main line index. Remarkable variations, which are rare in normal hands, were frequently observed. The results deviated from the normal range in cases of ectrodactyly and syndactyly, but were within the normal range in cases of polydactyly. The dermatoglyphics associated with each type of hand anomaly was characteristic and discriminative. Dermatoglyphics was also helpful in evaluating the function of the hand, and in estimating the time of the damage to the hand in embryogenesis. PMID- 7876497 TI - Tissue expansion for the treatment of complete syndactyly of the first web. AB - Tissue expansion is a well-established technique for the management of soft tissue deficiencies. In congenital hand surgery the construction of an adequate first web is paramount. We used tissue expansion in four hands in three patients with complete complex syndactyly of the first web space. Two of these patients had Apert's syndrome and the other an isolated mitten hand anomaly. The expander is preferably placed early in life so that first web construction is completed in the first year. Tissue expander ports are left exposed. There have been no infections, flap or expander loss in our series. PMID- 7876498 TI - Thumb duplication, 66 years' experience--a review of surgical complications. AB - Fifty-four supernumerary thumbs excisions were followed for an average of 9 years for results of their surgical management, which consisted of simple excision (16 patients), reconstructive procedures (33 patients), or central wedge resections (5 patients). Half of all simple excisions and reconstructive procedures gave unacceptable results, most were salvaged. These were primarily joint deviations, joint instabilities, and bony prominences. All of our central wedge resections gave unacceptable results that were not salvageable--short, stiff, fat thumbs with nail deformities. We feel this procedure should probably be reserved for cases where both digits of the supernumerary thumbs are severely hypoplastic. PMID- 7876499 TI - Congenital proximal radioulnar synostosis: treatment with the Ilizarov method. PMID- 7876500 TI - A biomechanical comparison of techniques of flexor tendon repair. AB - Achieving satisfactory digital motion after suturing severed flexor tendons remains a challenge. Although a suture technique proposed by Savage is stronger in vitro than a true Kessler repair, the Savage technique has not been previously tested in vivo. We repaired 96 severed canine tendons using either of two modifications of the Kessler technique or the Savage technique. The tensile strength of these repairs were compared at 0, 1, 3, and 6 weeks after suturing. The Savage technique provided a significantly stronger repair than the "suture locking" method in vitro and at 1 and 3 weeks after repair. We found no significant differences between the tensile strengths of the Kessler-Tajima and suture-locking methods at any time. PMID- 7876501 TI - Tendon repair using flexor tendon splints: an experimental study. AB - Mechanical strength of tendon repair using Dacron tendon splints across the laceration site were evaluated in human cadaver profundus tendons; the splints were placed both on the dorsal surface and internally within the tendon substance. Comparison was made to modified Kessler, Becker, and Savage repair techniques. Ultimate tensile strength was 2.55 kgf for the Kessler, 3.00 kgf for the Becker, 8.29 kgf for the Savage, 8.46 kgf for the internal tendon splint, and 8.10 kgf for the dorsal tendon splint; the Savage and both Tendon Splints techniques had significant higher tensile strength than the Kessler and Becker. Gap strength was 1.44 kgf for the Kessler, 2.22 kgf for the Becker, 2.45 kgf for the Savage, 2.05 kgf for internal tendon splint, and 3.15 kgf for the dorsal tendon splint. The dorsal tendon splint technique showed significant greater gap strength than the other four techniques. There was no significant difference in the magnitude of the gap during cyclic testing of these techniques; however, three of seven Kessler repairs failed and one of six Becker repairs failed. The results of these cadaver studies suggest that both tendon splint repair techniques are comparable to the Savage and may have sufficient strength to allow postoperative active motion against minimal resistance. Further in vivo testing is in order. PMID- 7876502 TI - Early active short arc motion for the repaired central slip. AB - This study compared the functional results in patients with open and repaired central slip injuries treated by two different postoperative management methods. The groups were similar in number of patients and amount of complex injuries. The comparisons made were proximal interphalangeal joint extensor lag, flexion at distal interphalangeal and proximal interphalangeal joints, total active motion, and length of treatment required. Patients in group 1 were treated with 3-6 weeks of continuous immobilization followed by a vigorous standard rehabilitation program. Patients in group 2 were treated by early active short arc motion initiated between the second day and the eleventh day after repair. By all criteria evaluated, patients in group 2 demonstrated better results at discharge compared to patients in group 1. PMID- 7876503 TI - A case report and review of mycetoma of the hand: a diagnostic and therapeutic challenge. PMID- 7876504 TI - Fecal occult blood testing in hospitalized patients. AB - We have evaluated the diagnostic value of the fecal occult blood test (FOBT) in hospitalized patients. We reviewed the medical records of patients who had a positive FOBT not associated with a large gastrointestinal bleed, and who had a subsequent complete evaluation of their gastrointestinal (GI) tract. Of the 50 subjects who met the study criteria, 21 had various GI symptoms and 13 reported weight loss. Patients taking medications that may influence the FOBT result were distributed as follows: 15 were taking nonsteroidal antiinflammatory drugs, eight were taking iron supplementation, three were using steroid drugs, and three were taking anticoagulant drugs. Nonneoplastic lesions were found in 47 patients. Neoplastic lesions were discovered in 11 patients: seven had adenomatous polyps, two had colorectal cancer, one had gastric cancer, and one had duodenal cancer. Only two of seven patients with adenomatous polyps had lesions > 1 cm. In the study population, the positive predictive value of FOBT for finding colonic neoplasms was 18% and for any GI neoplasm it was 22%. Our data indicate that in hospitalized patients (a) the yield of colonic neoplasms from FOBT is approximately 50% less than that in healthy outpatients, and (b) a positive FOBT test is unlikely to lead to the detection of GI malignancy in the absence of suggestive clinical findings. PMID- 7876505 TI - A randomized, double-blind, placebo-controlled trial of the oral mesalamine (5 ASA) preparation, Asacol, in the treatment of symptomatic Crohn's colitis and ileocolitis. AB - Oral mesalamine (Asacol) in a dose of 3.2 g/day was administered in a 16-week placebo-controlled trial in 38 patients for the treatment of mildly to moderately active Crohn's colitis or ileocolitis. Eighteen patients continued a stable dose of prednisone of no more than 20 mg/day and 20 patients did not take prednisone. Changes in the Crohn's Disease Activity Index (CDAI) were used as the primary measure of efficacy. Oral mesalamine was effective in achieving partial or complete remission in 60% of patients as compared with 22% of placebo-treated patients. However, only 20 of 38 patients completed the 17-week study. The others withdrew early because of worsening of symptoms or were dropouts counted as failures. The high percentage of early withdrawals prevented comparison of mean 17-week CDAI scores. Although the number of patients in this study was relatively small, Asacol 3.2 g/day appears to be safe and effective treatment for mildly to moderately active Crohn's colitis and ileocolitis as compared with placebo, and this regimen is an option for treatment of patients who fail or are intolerant of sulfasalazine. PMID- 7876506 TI - Major hemorrhage from endoscopic sphincterotomy: risk factor analysis. AB - We carried out a retrospective cohort study on all patients undergoing sphincterotomy at our institution over a 4-year period. Major hemorrhage occurred in 10 of 189 patients (5.3%). Onset was usually delayed (mean, 3.0 days; range, 0 9 days). Six potential risk factors for postsphincterotomy hemorrhage were assessed by univariate and multivariate analysis. Three factors predicted postsphincterotomy hemorrhage: hemodialysis (relative risk, 8.4; 95% confidence interval, CI, 2.7-26.4), a prothrombin time prolonged at least 2 s above control (relative risk, 7.8; 95% CI, 2.4-25.6), and endoscopically observed bleeding at the time of sphincterotomy (relative risk, 5.9; 95% CI, 1.7-20.1). Features not independently associated with hemorrhage were sphincter of Oddi dysfunction, aspirin or nonsteroidal anti-inflammatory drug (NSAID) use within 1 week prior to sphincterotomy, and sphincterotomy length. When differentiated from endoscopically observed bleeding, clinically significant hemorrhage was usually a delayed complication, primarily in patients with hemostatic defects. PMID- 7876507 TI - Cryptosporidium. A cause of gastroenteritis in preschool children in Jordan. AB - In this case-control study, we investigated the role of Cryptosporidium in gastroenteritis in children < 6 years old. Six hundred fresh stool specimens were examined for various pathogenic parasites, bacteria, and rotaviruses. Wet-mount preparations, formaline-ether concentrations, and Sheather's floatation techniques were used to recover the parasite oocysts. Permanent stained slides using acid-fast stain and trichrome stains were prepared. Of 300 children with gastroenteritis symptoms, 20 (6.7%) had Cryptosporidium oocysts; seven of the 20 had concomitant infections so they were excluded from the counts. This infection rate is significantly different (Z = 2; p < 0.05) from that found in the control group (1.7%) of children who reported no symptoms. The most frequent symptoms reported beside diarrhea were abdominal pain, cramps, anorexia, nausea, vomiting, and fatigue. Contaminated drinking water is suspected to be the source of infection; other possible factors are discussed. PMID- 7876508 TI - The gastrointestinal manifestations of gunshot-induced lead poisoning. AB - Lead poisoning associated with gunshot is not unknown but, unless suspected, can be easily missed. We describe a patient with lead intoxication following a gunshot injury, who presented with abdominal colic, anorexia, and weight loss as initial manifestations. He had extremely high blood lead levels and the onset of lead poisoning was comparatively rapid. We review the recent English language literature (1980-1993) related to lead poisoning due to lead projectiles with particular emphasis on mechanisms responsible for its gastrointestinal manifestations. PMID- 7876509 TI - The effect of total parenteral nutrition on serum albumin. AB - Our objective was to assess whether the serum albumin level rises in patients given total parenteral nutrition (TPN). All randomized controlled studies of TPN for at least 7 days versus oral therapy were reviewed. Data on serum albumin had to be available to be acceptable for analysis. Only trials of patients with cancer fulfilled these selection criteria for our analysis. None of the reported studies showed a significant rise in serum albumin with TPN when compared to controls. The mean change in serum albumin levels for all of the studies was -0.3 g/dl in the TPN group and -0.3 g/dl in the control group. In published randomized controlled studies of TPN versus oral diet, there is no significant increase in serum albumin levels in those receiving TPN or decrease in serum albumin in controls. Our study does not support the serum albumin level as a nutritional marker in patients with cancer. PMID- 7876510 TI - Combined duodenal and colonic necrosis. An unusual sequela of caustic ingestion. AB - Two unusual cases of liquid caustic ingestion that resulted in gangrene of the duodenum and adjacent colon, and burns of the esophagus, stomach, and pancreas are presented. The routine evaluation of the oropharynx, esophagus, and stomach after liquid caustic ingestion can seriously underestimate the extent of injury to distal portions of the gastrointestinal (GI) tract, such as the colon and pancreas, that are not usually included in the initial evaluation of ingestion injuries. In stable patients managed nonoperatively, the entire upper GI tract, including the duodenum, must be visualized either by endoscopy or, less preferably, by barium series. Double-contrast computed tomography should be performed when significant duodenal injuries are present in order to inspect the colon, pancreas, and small bowel. With this approach, life-threatening, multi organ, subdiaphragmatic ingestion injuries can be identified and treated early. PMID- 7876511 TI - Cytomegalovirus as an exacerbating factor in ulcerative colitis. AB - Cytomegalovirus (CMV) colitis has been reported infrequently in patients with underlying inflammatory bowel disease, and usually in those who are taking long term corticosteroid drugs and who are potentially immunosuppressed. We report a 39-year-old man with long-standing ulcerative colitis, taking only sulfasalazine, who developed a viral prodrome followed by bloody diarrhea. Severe colitis was noted on endoscopy. He worsened with intravenous steroid and antibiotic drugs. Flexible sigmoidoscopy with biopsy before a contemplated colectomy revealed a moderately active colitis with large cells containing intranuclear inclusions scattered throughout the biopsies, characteristic of CMV colitis. Serologic and immunologic studies suggested recent CMV infection. The patient improved with intravenous ganciclovir and a steroid taper, and colectomy was avoided. CMV colitis is a potentially treatable cause of fulminant colitis. PMID- 7876512 TI - Portal hypertensive gastropathy in splenic vein thrombosis. AB - Portal hypertensive gastropathy has been related to portal hypertension and is a recognized cause of iron deficiency anemia. Although this gastric mucosal lesion has been occasionally described in extrahepatic portal hypertension, its clinical significance and histological features are not well established. We report a case of chronic anemia due to portal hypertensive gastropathy in a patient with splenic vein thrombosis, and suggest that the cure of gastric lesions in this condition may be obtained by splenectomy. PMID- 7876513 TI - Idiopathic chronic active hepatitis: a diagnostic and therapeutic dilemma. AB - A 56-year-old Saudi male was admitted with abnormal liver chemistry values and a > 5-month history of lethargy, malaise, anorexia, and jaundice. Extensive investigations did not establish an etiological diagnosis. Liver histology confirmed the clinically apparent aggressive hepatitis with fibrosis but gave no clue to its etiology. The patient was empirically treated with alpha-interferon for presumed non-A, non-B hepatitis, with clinical and biochemical worsening. Interferon was discontinued and the patient was started on immunosuppression. Dramatic clinical and biochemical improvement occurred, with normalization of the liver chemistry within 4 weeks. The patient has been followed-up for 12 months and has not suffered a relapse. This case highlights the etiological heterogeneity of chronic active hepatitis. The entity of autoimmune chronic active hepatitis is unclear, and perhaps it is better defined as steroid responsive hepatitis. Steroid-responsive hepatitis should always be considered in cases of cryptogenic chronic active hepatitis. PMID- 7876514 TI - Malakoplakia of liver associated with a perforated colonic diverticulum. A case report and review of the literature. AB - Malakoplakia of the liver is rare, only three cases having been documented in the world literature. Described here is the first case of malakoplakia of the liver as a complication of a perforated colonic diverticulum. PMID- 7876515 TI - Gastric heterotopia in the upper esophagus (inlet patch) in endoscopic surveys in northern China. AB - Upper esophageal gastric heterotopia (inlet patch) has not been reported in endoscopic series from China. We describe the occurrence of endoscopically and histologically typical inlet patches in two endoscopic surveys of asymptomatic adults in northern China. Because rapid endoscopic protocols were used, the 0.3 0.4% prevalence of inlet patch in these surveys probably represents a minimum figure for adults in this population. PMID- 7876516 TI - Laparoscopic cholecystectomy: from gimmick to gold standard. AB - Laparoscopic cholecystectomy was first performed in 1987, and within 2 years had become widespread. Its rapid growth was due in part to a perceived reduction in postoperative morbidity and shorter convalescence than with open cholecystectomy. Although these perceptions were shared both by surgeons and the lay public, no controlled study has documented them conclusively, but now, because of its popularity, it is unlikely that such a study will ever be undertaken. Nevertheless, a wealth of information has been accumulated on open cholecystectomy, and a large body of data is being generated regarding laparoscopic cholecystectomy. We examine selected reports of both laparoscopic and open cholecystectomy in terms of incidence and outcome. Our review supports the notion that laparoscopic cholecystectomy is safe and effective, has an acceptable complication rate, and a considerably shorter convalescence. Thus, laparoscopic cholecystectomy is now the treatment of choice for symptomatic cholelithiasis, and is becoming the new gold standard against which other procedures should be judged. PMID- 7876517 TI - Acute abdominal pain in the elderly. AB - In this article, I review the diagnosis and immediate prognosis of acute abdominal pain in elderly patients. I draw on published work and on three major series of patients, one collected since 1976 by the World Organization of Gastroenterology (OMGE) Research Committee, one by the 1986 United Kingdom National Study of Human and Computer-Aided Diagnosis, and one by the European Community 1993 Concerted Action on Acute Abdominal Pain. These series include approximately 42,000 patients. Acute abdominal pain in the elderly patient presents a significant and challenging problem. Diagnostic accuracy is lower, and mortality far higher, than in younger patients. Reasons for these differences are multifactorial: the case mix is different, the evolution and prognosis of specific diseases are different, and the ways in which diseases present are also different in elderly patients. It is not difficult therefore to understand why serious problems in management occur. I conclude by discussing implications of existing studies and the literature that--if implemented--should significantly improve both management resource utilization and patient outcome. PMID- 7876518 TI - Cisapride increases micturition frequency. PMID- 7876519 TI - Carcinoid tumor of the esophagus. PMID- 7876520 TI - Bronchiolitis obliterans in ulcerative colitis. PMID- 7876521 TI - Focal hemorrhagic necrosis of the liver: related to the use of the oral contraceptive pill? PMID- 7876522 TI - Fatal hemorrhage following laser hemorrhoidectomy. PMID- 7876523 TI - Spontaneous peritonitis caused by Streptococcus bovis. PMID- 7876524 TI - Treatment for Helicobacter pylori infection. PMID- 7876526 TI - A rare case of secondary appendicitis. PMID- 7876525 TI - Sulfasalazine, 5-ASA and acute pancreatitis in crohn's disease. PMID- 7876527 TI - Interpreting the history of bloodletting. PMID- 7876528 TI - The life of the corpse: division and dissection in late medieval Europe. PMID- 7876529 TI - Anatomy as rhetoric: Galen on dissection and persuasion. PMID- 7876530 TI - Attitudes toward dissection in medieval Islam. PMID- 7876531 TI - DMA and DMB are the only genes in the class II region of the human MHC needed for class II-associated antigen processing. AB - Previous studies have shown that homozygous mutations between the LMP2 and DNA loci in the human MHC cause class II molecules to be abnormally conformed and unstable in the presence of SDS at low temperature, and impede class II associated Ag processing and presentation. These abnormalities result from impaired ability to form intracellular class II/peptide complexes that predominate in normal cells. We show in this work that this defect results from deficient expression of either the DMA or the DMB gene. Human B-LCL.174 (DR3) cells, which have a deletion of all known expressible genes in the class II region, express transgene-encoded HLA-DR3, but have the abnormalities. Transfer of cosmid HA14, which contains the DMA and DMB genes, into .174 (DR3) cells restored normal DR3 conformation, stability in 0.4% SDS at 0 degree, and ability to process and present tetanus toxoid, but only when both DMA and DMB mRNAs were present. The requirement for both genetic expressions in engendering normal phenotypes was confirmed by transferring the cloned genes into .174 (DR3) cells separately or together. Because normal phenotypes were fully restored in transferent cells expressing DMA plus DMB, other genes in the approximately 1-mb homozygous class II region deletion in .174 (DR3) cells either do not participate in or are dispensable for apparently normal production of intracellular class II/peptide complexes. The properties of DM-deficient EBV-transformed B lymphoblastoid cell lines (LCLs) suggest ways of identifying humans in whom DM deficiency contributes to congenital immunodeficiency and malignancy. PMID- 7876532 TI - Intraembryonic origin of hepatic hematopoiesis in Xenopus laevis. AB - The liver is a major site of hematopoietic stem cell differentiation during vertebrate development. Hepatic hematopoiesis is dependent on colonization of the organ by extrinsically derived stem cells which, in mammals, are thought to originate only in the yolk sac. However, in birds and amphibians two distinct embryonic stem cell sources have been identified. The yolk sac or extraembryonic compartment is associated with the developing vitelline veins, and the para aortic or intraembryonic compartment is associated with the dorsal aortae and postcardinal veins. The homologous compartments in the Xenopus embryo are the ventral blood island (extraembryonic) and dorsal lateral plate (intraembryonic) mesoderms, which contribute to primitive larval erythrocyte and definitive late larval and adult erythroid populations, respectively. The role of these embryonic stem cell sources in hepatic hematopoiesis has not been determined. We have examined the development of hepatic hematopoiesis in Xenopus 2N/3N stem cell chimeras using two-color FACS analysis. DNA content was determined using Hoechst 33342, and subpopulations of hematopoietic cells were identified with specific mAbs. Here we show that hepatic erythrocytes, leukocytes, and B lymphocytes in the liver of Xenopus larvae were derived from stem cells that originated from the intraembryonic mesoderm. PMID- 7876533 TI - Hybrid and allogeneic resistance to T cell grafts mediated by murine NK and CD8+ T cells. AB - Lethally irradiated mice can reject H-2 allogeneic or parental strain stem cells in bone marrow cell (BMC) grafts within 48 h after transplantation. This rapid rejection of BMC grafts occurs without prior sensitization and is mediated by NK1.1+ NK cells. One hypothesis to account for the ability of host NK cells to mediate acute rejection of allogenic and parental stem cells is that these effector cells recognize hemopoietic histocompatibility (Hh-1) Ags on the donor stem cells. T cells present in the donor BMC can prevent NK cell-mediated rejection. However, lethally irradiated mice can also reject T cells present in lymph node cell preparations that respond to alloantigens of the host. T cell grafts from H-2k/Hh-1k, H-2r/Hh-1null, and H-2ia1/Hh-1null donors were rejected by CD8+ NK1.1- T cells. Ags other than Hh-1 Ags appeared to be recognized by these CD8+ T cells. In contrast, host NK cells rejected H-2d/Hh-1d T cell grafts, whereas both NK cells and CD8+ TCR-alpha beta + T cells rejected H-2b/Hh-1b T cell grafts. Therefore, both CD8+ TCR-alpha beta T cells and NK cells mediate allogeneic and hybrid resistance to T cell grafts. PMID- 7876534 TI - IL-12 inhibits IL-4 synthesis in keyhole limpet hemocyanin-primed CD4+ T cells through an effect on antigen-presenting cells. AB - Although IL-12 is known to enhance IFN-gamma synthesis in unprimed CD4+ T cells, the effect of IL-12 on IL-4 synthesis in primed CD4+ T cells, which are thought to have relatively fixed cytokine profiles, has not been clearly examined. We examined the effects of IL-12 on cytokine production by CD4+ keyhole limpet hemocyanin (KLH)-primed memory lymph node T cells and by already established KLH specific CD4+ T cell clones. First, we found that the presence of IL-12 greatly reduced the development of IL-4 synthesis in resting but not activated memory CD4+ T cells. Although IL-12 did not inhibit the production of IL-4 in cloned Th2 effector cells, it greatly inhibited the development of IL-4 synthesis in primed CD4+ T cells taken from the lymph nodes of mice previously immunized with KLH. Secondly, we found that IL-12 inhibited IL-4 synthesis either when directly added to cultures of T cells or when APC were preincubated in IL-12. Inasmuch as the enhancing effect of IL-12 on IFN-gamma synthesis occurred optimally only when the T cells were cultured directly in IL-12, these studies indicate that IL-12 affects IL-4 synthesis via a mechanism that involves APC, a process that differs from that by which it affects IFN-gamma synthesis. These studies also indicate that the administration of IL-12 would be clinically useful in treating patients, for example those with allergic disease or lepromatous leprosy, in whom memory T cells inappropriately overproduce IL-4. PMID- 7876535 TI - Selective expansion followed by profound deletion of mature V beta 8.3+ T cells in vivo after exposure to the superantigenic lectin Urtica dioica agglutinin. AB - Urtica dioica agglutinin (UDA) is a superantigen that, in vitro, binds to specific carbohydrate structures on class II and induces a sixfold enrichment of V beta 8.3+ BALB/c mice splenic T cells. Superantigens have pleiotropic effects in vivo, causing the activation, proliferation, and deletion of specific T cells, but are heterogenous in regard to their effects on T cell tolerization. We, therefore, compared the responses of peripheral T cells from adult BALB/c mice with the i.v. injection of 50 micrograms UDA or the bacterial superantigen staphylococcal enterotoxin B (SEB) that also recognizes the V beta 8.3 gene product. The data presented indicate that activation, clonal expansion, anergy, and death of V beta 8.3+ T cells occur sequentially after UDA administration. Two days after UDA injection, the proportion of V beta 8.3+ T cells in the periphery is elevated to approximately twice that of normal mice. This expansion occurs in both CD4+ and CD8+ subsets. V beta 8.3+ T cells from UDA-primed mice are anergic to UDA restimulation and fail to proliferate or to produce IL-2. Futhermore, the proliferation of V beta 8.3+ T cells is followed by their rapid disappearance concomitant with their specific elimination by apoptosis. In 1 wk, all CD4+ V beta 8.3+ peripheral T cells are deleted. The decline of V beta 8.3+ T cells in the CD4+ subset is more than in the CD8+ subset. This occurs in thymectomized and in thymus-intact animals. Two months after UDA priming, the percentage of V beta 8.3+ T cells is still lower than in control mice. PMID- 7876536 TI - Engagement of CD27 with its ligand CD70 provides a second signal for T cell activation. AB - Molecules of the TNF-R family have been shown to be essential in the regulation of lymphocyte growth and differentiation. The TNF-R family member CD27 binds to a type II transmembrane molecule belonging to the TNF gene family (CD27L) that is identical to the lymphocyte activation Ag CD70. Using transfected mouse fibroblasts expressing human CD70, we demonstrate here that interaction of CD27 with its ligand provides a potent second signal for cytokine production, induction of activation Ags, and proliferation of unprimed CD45RA+, and to a lesser extent, of primed CD45R0+ peripheral blood T cells. In contrast to costimulatory signals delivered via the CD28-ligand B7-1 (CD80), CD70 was found to induce relatively low IL-2, IL-4, and IL-10 but comparable TNF-alpha secretion. Proliferation of CD45RA+, but not of CD45R0+ T cells, was found to be largely resistant to blocking of IL-2/IL-2R interaction. Finally, the finding that CD70 and CD80 cooperate in the induction of T cell proliferation indicates that cooperation of both molecules may be essential for optimal T cell stimulation. The interaction between CD27 and its ligand CD70 might be of particular importance for the recruitment of T cells from the unprimed T cell pool. Moreover, as CD70 expression in vivo is confined to activated B and T lymphocytes, only a limited set of APC are able to generate this specific second signal for T cell expansion. PMID- 7876537 TI - A cascade of cytokines is responsible for IL-9 expression in human T cells. Involvement of IL-2, IL-4, and IL-10. AB - We have previously demonstrated that IL-9 induction in human T cells stimulated with PMA and anti-CD3 Ab is mediated by IL-2, as it was blocked by anti-IL-2R Ab. The experiments reported here indicate that anti-IL-2R Ab also inhibited the expression of IL-4, IL-6, and IL-10, thereby raising the possibility that the blockade of IL-9 production by anti-IL-2R mAb could be secondary to the blockade of these cytokines. We found that the inhibition caused by anti-IL-2R Ab on IL-9 production could be reversed by the addition of a combination of IL-4 and IL-10. Moreover, IL-9 production by T cells stimulated with PMA and anti-CD3 Ab was blocked by the addition of anti-IL-4 and anti-IL-10 Abs. Similar results were obtained with T cells cultured on B7-1/Fc gamma RII-transfected fibroblasts in the presence of anti-CD3 Ab. Analysis of cytokine production by different T cell subsets revealed that IL-4, IL-9, and IL-10 were produced only by CD45 Ro+ T cells. Importantly, CD45 Ra+ T cells were capable of producing IL-9 provided that both IL-4 and IL-10 were added to the cultures. The possible relationship between IL-4 production and IL-10 production was clarified by experiments indicating that IL-10 production was inhibited by anti-IL-4 Ab. However, IL-4 was not sufficient to trigger IL-10 production, which required both IL-2 and IL-4. Taken together, our results demonstrate the existence of a cascade of cytokines responsible for IL-9 expression, with IL-2 being required for IL-4 production, a combination of IL-2 and IL-4 for IL-10 production, and a combination of IL-4 and IL-10 for IL-9 production. Kinetics studies of cytokine gene expression in T cells further validated this model. PMID- 7876538 TI - NK cell recognition of MHC class I. NK cells are sensitive to peptide-binding groove and surface alpha-helical mutations that affect T cells. AB - NK cells directly or indirectly recognize MHC class I molecules, but the exact structures recognized remain poorly defined. We address the hypothesis that NK cells, like T cells, directly contact peptide/MHC class I complexes. This hypothesis predicts that NK-mediated killing is inhibited by amino acid substitutions in the MHC class I peptide-binding groove and in solvent-accessible alpha-helical residues proposed to contact the TCR. In our model system, target cell HLA-B*0702 inhibited killing by unstimulated peripheral blood NK cells. NK mediated killing was increased significantly by 6 of 11 peptide-binding groove mutations and 6 of 12 TCR contact site mutations, but only 1 of 6 mutations outside these sites. Many of the mutations that inhibited NK-mediated killing prohibited killing by 12 alloreactive CTL clones. These data suggest that NK receptors directly contact HLA-B*0702, focusing on the peptide-binding groove and surrounding alpha-helices. NK cell lines exhibited multiple HLA recognition patterns, which is consistent with nonuniform expression of MHC receptors by NK cells. We propose that NK cells, like alpha beta T cells and some anti-MHC Abs, directly or indirectly recognize MHC-bound peptides. PMID- 7876539 TI - Immobilized anti-CD3 antibody activates T cell clones to induce the production of interstitial collagenase, but not tissue inhibitor of metalloproteinases, in monocytic THP-1 cells and dermal fibroblasts. AB - In this study we have investigated whether direct cell to cell contact between activated paraformaldehyde-fixed T cell clones obtained from synovial tissue of patients with osteoarthritis (OA) or rheumatoid arthritis and target monocytic cells or dermal fibroblasts influenced the balance between interstitial collagenase and its specific inhibitor tissue inhibitor of metalloproteinases (TIMP) produced by the latter cell types. PHA/PMA-activated fixed T cell clones or their membranes strongly induced the production of collagenase both in monocytic THP-1 cells and in dermal fibroblasts. In contrast, only low levels of TIMP were induced in THP-1 cells and no change of TIMP expression was observed in fibroblasts as a result of stimulation with PHA/PMA-activated T cells or T cell membranes. Anti-CD3-activated T cell clones stimulated the production of collagenase both in THP-1 cells and fibroblasts, whereas TIMP levels were not influenced. Collagenase production in THP-1 cells induced by anti-CD3-activated T cell clones was 1) dependent on the dose of anti-CD3 used to stimulate the T cells, 2) initiated only when CD3 was cross-linked, and 3) inhibited when cyclosporin A was included during T cell activation. Our data collectively indicate that activated T cells in contact with monocytic cells or fibroblasts may alter the balance between interstitial collagenase and its specific inhibitor TIMP. This selective induction of a mediator profile representative of matrix breakdown as a result of target cell interaction with activated T cells may be an important factor in the local process of tissue destruction that characterizes osteoarthritis and rheumatoid arthritis. PMID- 7876540 TI - Analysis of the intra-epithelial lymphocyte compartment in SCID mice that received co-isogenic CD4+ T cells. Evidence that mature post-thymic CD4+ T cells can be induced to express CD8 alpha in vivo. AB - Severe combined immunodeficient (SCID) mice injected with co-isogenic CD4+/CD45RBhigh lymph node T cells from normal donors develop a wasting disease that is caused by hyperplasia of the intestinal epithelium. SCID mice injected with purified lymph node CD4+ T cells or CD4+/CD45RBlow T cells do not develop the disease. The IEL compartment from SCID mice injected with highly purified CD4+/CD45RBhigh T cells or CD4+ T cells contained significant numbers of T cells that expressed both CD4 and CD8 alpha, but not CD8 beta. The CDr+/CD8 alpha + T cells were unique to the IEL compartment of the small intestine and were not observed in significant numbers in the lamina propria, mesenteric lymph node, nor IEL compartment of the large intestine. By using Ly-5 mismatched donors and recipients, we determined that the CD4+/CD8 alpha + T cells were derived from the donor T cells. The expression of CD8 alpha was stable in vitro, and CD8 alpha mRNA was detected in sorted CD4+/CD8 alpha + T cells by reverse transcriptase-PCR (RT-PCR). Recombinase-activating gene (RAG)-1 and -2 mRNA was not detected in the intra-epithelial lymphocyte CD4+/CD8 alpha + T cell population. Thus, it appears that under conditions unique to the epithelial layer of the small intestine, mature post-thymic CD4+ T cells can be induced to express CD8 alpha. PMID- 7876541 TI - Anti-IL-4 antibody prevents graft-versus-host disease in mice after bone marrow transplantation. The IgE allotype is an important marker of graft-versus-host disease. AB - Induction of a graft-vs-host reaction in irradiated (BALB/c X C57BL/6)F1 mice (CBF1 mice) with bone marrow cells (BMC) plus spleen cells of BALB/c mice leads to bone marrow transplantation--GVHD (BMT-GVHD). BMT-GVHD is characterized by liver disease, splenomegaly, and hypergammopathy. In addition, we found that increased serum IgE and IgG1 levels were correlated with BMT-GVHD such as liver disease and splenomegaly. The allotype of increased IgE levels in BMT-GVHD was IgEa of donor origin, not IgEb of host origin. We also found that in the thymus of murine BMT-GVHD, the CD4+ CD8+ double-positive T cells were decreased, but the CD4+ CD8- or CD4- CD8+ single-positive T cells were increased. Interestingly, double-positive T cells appeared in the spleen, suggesting that abnormal T cell differentiation existed in murine BMT-GVHD. When the recipients were treated with anti-IL-4 Ab (11B11), the increase of IgE and IgG1 was markedly reduced and liver disease and splenomegaly were also prevented. Moreover, abnormal T cell differentiation and maturation were suppressed. These observations suggest that IL-4 plays an important role in immunoregulation or pathogenesis of allogeneic effects, and 11B11 prevents immunodysfunction including T cell differentiation in the thymus or the spleen and autoimmune symptoms in murine BMT-GVHD. PMID- 7876542 TI - Successive generation of antigen-presenting, dendritic cell lines from murine epidermis. AB - Dendritic cells are specialized APCs that exhibit an extraordinary capacity to activate naive T cells. Langerhans cells (LC), as epithelial tissue-specific members of this family, play key roles in the induction of T cell-mediated immunity against environmental, infectious, and tumor-associated Ags in skin. A major limitation in studying the biology of dendritic cells or LC has been the absence of stable, long-term cell lines. To overcome this limitation, we have established a series of APC lines (XS series) from newborn BALB/c mouse epidermis. XS lines, which have grown for more than 12 mo in culture, exhibit high similarity to LC freshly procured from skin in terms of: a) tissue of derivation (epidermis), b) phenotype (lalow/CD45+/E-cadherin+/B7-1-), c) shape (elongated dendrites), and d) Ag-presenting profile (modest ability to activate naive, allogeneic T cells and remarkable ability to present a protein Ag to primed CD4+ T cells). The availability of XS lines as well as the methodologies used for their growth enhance our capability of studying the biology of LC at biochemical and molecular levels. PMID- 7876543 TI - Molecular cloning of a cDNA clone encoding a phosphoprotein component related to the Ig receptor-mediated signal transduction. AB - We have shown previously that a 52-kDa phosphoprotein (p52) co-precipitated with Ig receptor (IgR)-associated MB-1 protein was inducibly phosphorylated by the stimulation with 12-O-tetradecanoyl-phorbol-13-acetate. By immunizing the 52-kDa protein co-precipitated with MB-1, we prepared a mAb (19-14), which can immunoprecipitate the p52 and the associated kinase molecule. Immune complex kinase assay with the 19-14 mAb showed that the p52 is associated with a novel kinase molecule and is involved in IgR-mediated signal transduction. Here we isolated a cDNA clone (alpha 4) from a murine bone marrow cDNA library in lambda gt-11 vector by the 19-14 mAb. The alpha 4 cDNA encodes a novel protein of 340 amino acids with multiple potential phosphorylation sites. The 1.4-kb alpha 4 mRNA is expressed in various cells including cell lines of B lineage, T lineage, monocytic, fibroblast, and normal organs such as liver, spleen, thymus, and brain. To study the molecule encoded by the alpha 4 cDNA, we produced a chimeric protein of the glutathione S transferase (GST)-alpha 4 in pGEX-3X expression vector. The 19-14 mAb binds to the GST-alpha 4 fusion protein. Rabbit anti-alpha 4 Ab prepared by immunizing the GST-alpha 4 fusion protein immunoprecipitated a 52-kDa phosphoprotein from WEHI-231 cells. The 52-kDa phosphoprotein immunoprecipitated by the anti-alpha 4 Ab is tightly associated with kinase activity that is similarly observed with the p52 protein reported previously. Moreover, the 52-kDa phosphoprotein immunoprecipitated with the anti-alpha 4 Ab is identical to the p52 by the protein comparison on non-equilibrium pH gradient gel electrophoresis/SDS-PAGE, isoelectric focusing/SDS-PAGE, and V8 protease mapping. The 52-kDa phosphoprotein is associated with functional components that are inducibly phosphorylated by anti-IgM stimulation. These results suggested that the alpha 4 gene-encoded molecule is functionally involved in the IgR mediated signal transduction in B cells. PMID- 7876544 TI - Role of ETS1 in IL-2 gene expression. AB - The ETS1 gene encodes a sequence-specific transcription factor binding to purine rich DNA sequences (-GGAA-) present in the transcriptional regulatory regions of many cellular and viral promoters/enhancers, including many lymphokine genes. The ETS1 gene is expressed at high levels in resting T cells and at very low levels after T cell activation, suggesting it may suppress the expression of genes induced during T cell activation. To find out if ETS1 regulates expression of the IL-2 gene, we have ectopically expressed antisense (AS) ETS1 in Jurkat T cells to block the formation of ETS1 proteins. AS ETS1 transfectants produce higher levels of IL-2 compared with sense ETS1 transfectants. Expression of ETS1 DNA binding domain in Jurkat T cells also decreased the production of IL-2. In AS ETS1 transfectants, IL-2 formation was completely inhibited by cyclosporin A and FK590. The IL-2 promoter linked to a chloramphenicol acetyl transferase reporter gene has high activity in AS ETS1 transfectants, indicating that increased IL-2 production seems to be a result of transcriptional induction. Taken together, these results suggest the possibility that ETS1 may act as a negative regulator of IL-2 gene transcription and provide a rational approach toward engineering the endogenous expression of IL-2 in T cells. PMID- 7876545 TI - Structure of the mouse CD72 (Lyb-2) gene and its alternatively spliced transcripts. AB - The complete sequence of the CD72 gene from the C57L mouse, including the 5' and 3' flanking sequences, is reported. The gene spans 6830 base pairs and includes nine exons surrounding eight introns. It does not have an obvious TATAA box, so it belongs to a group of genes with TATA-less promoters that are regulated during mammalian immunodifferentiation. cDNA sequence comparisons among CD72a, CD72b, and CD72c alleles have demonstrated two distinct seven amino acid insertion/deletions among these allelic variants. Based on our genomic sequence studies as well as PCR analyses, we found that different strains of mice can alternatively or exclusively use either of two AG sites surrounding the 21-bp insertion/deletions as 3' splice sites in an allele-specific manner. Other alternative splicing events, such as exon skipping, also contribute to CD72 polymorphism. In mouse splenic B cells there are allele-specific distributions of CD72 mRNAs that contain sequences from both exon 3 and exon 4, from either exon 3 or exon 4, or from neither exon 3 nor 4. It is unclear what the in vivo function might be of the proteins encoded by the mRNA forms lacking these exon sequences. PMID- 7876546 TI - Involvement of IFN-gamma in Bacillus Calmette-Guerin-induced but not in tumor induced sensitization to TNF-induced lethality. AB - In healthy mice, murine (m) TNF is fairly lethal, whereas human (h) TNF (a selective murine TNF-R55 agonist) is rather harmless. However, we and others observed that mice suffering from a bacterial infection, such as Bacillus Calmette-Guerin (BCG), or bearing i.m. some types of tumor, develop a hypersensitivity to the IL-6-inducing and lethal properties of hTNF. This is a cardinal problem as it severely limits the potential use of hTNF-R55-specific agonists for systemic treatment of human cancer. Using mice carrying a targeted disruption in the gene encoding the IFN-gamma receptor (IFN-gamma Ro/o), we here report that endogenous IFN-gamma plays a crucial role in the development of TNF hypersensitivity during BCG infection. Indeed, both the lethality and the IL-6 induced by hTNF were drastically reduced in IFN-gamma Ro/o mice as compared with control mice. These results demonstrate that the enhancement of TNF effects is at least an equally important mechanism by which IFN-gamma contributes to BCG induced hypersensitivity as the previously described augmentation of TNF production. Experiments in athymic nude mice, either depleted of NK cells or not, revealed that the latter cell population is an important source of the sensitizing IFN-gamma during BCG infection. In contrast, IFN-gamma Ro/o mice were as susceptible as control mice to the sensitizing effects of tumors. mTNF, which interacts with both mTNF-R55 and mTNF-R75 and causes lethality on its own, is as toxic in IFN-gamma Ro/o mice as in wt control mice; this means that TNF-induced IFN-gamma does not play a role in mTNF-induced lethality. PMID- 7876547 TI - Activation of IFN-alpha, IFN-gamma, MxA, and IFN regulatory factor 1 genes in influenza A virus-infected human peripheral blood mononuclear cells. AB - Mononuclear blood cells have an important role in immunity as they produce different cytokines in response to microbial infections. We infected primary human mononuclear blood cells with a pathogenic influenza A virus (A/Beijing/353/89) and studied the activation of IFN-alpha, IFN-gamma, IRF-1, and MxA genes. IFN-alpha and IFN-gamma steady state mRNA levels peaked at 6 to 9 h after infection and declined rapidly thereafter. Only a modest (twofold) increase in IRF-1 mRNA was seen. MxA gene expression, normally strictly regulated by IFN alpha/beta, had expression kinetics similar to those of IFN mRNA. Infection experiments done in the presence of cycloheximide showed that influenza virus infection could induce all genes studied in the absence of detectable protein synthesis. Pretreatment with IFN-alpha, but not with IFN-gamma, caused a dose dependent inhibition of influenza virus replication in PBMC, and this inhibition correlated with increasing levels of MxA protein. Influenza virus replication was also inhibited in a stably transfected, MxA-expressing promonocytic U937 cell line. The results suggest that MxA protein significantly contributes to IFN mediated host defence mechanisms against influenza A virus. PMID- 7876548 TI - IL-7 in the cell-mediated immune response to a human pathogen. AB - The goal of the present study was to investigate the role of IL-7 in regulating immune responses to infection. Leprosy provides a model for understanding human immune responses to infection; the disease presents as a spectrum in which the clinical manifestations correlate with the levels of cell-mediated immunity to the pathogen, Mycobacterium leprae. To determine whether IL-7 is produced at the site of infection in leprosy, we used the PCR to measure IL-7 and IL-7R mRNA in skin lesions. IL-7 mRNA was more strongly expressed in the tuberculoid form of the disease, in which the infection is limited (mean cpm = 48 +/- 8; n = 11), as compared with the progressive lepromatous form (17 +/- 2; n = 11). IL-7R mRNA, both membrane-bound and soluble forms, were also more strongly expressed in tuberculoid lesions, although these differences were not as striking as those for IL-7. The cellular source of IL-7 included Ag-stimulated monocytes and IFN-gamma induced keratinocytes. M. leprae-induced PBMC responses in tuberculoid patients involved up-regulation of IL-7 and IL-7R mRNA and was IL-7 dependent. In contrast, M. leprae did not induce IL-7 mRNA in lepromatous patients, and their T cell responses were weakly augmented by rIL-7. These data suggest that IL-7, produced at the site of disease, contributes to the cell-mediated immune response to human pathogens. PMID- 7876549 TI - Induction of protective polyclonal antibodies by immunization with a Plasmodium yoelii circumsporozoite protein multiple antigen peptide vaccine. AB - Monoclonal Abs against the repeat region of the circumsporozoite protein (CSP) completely protect mice against Plasmodium yoelii (Py), but synthetic peptide and recombinant protein vaccines designed to produce only Abs to the PyCSP repeat region have never been reported to consistently provide protection. This lack of protection in the rodent model system has predicted the poor protection achieved in humans after immunization with synthetic peptide and recombinant protein P. falciparum CSP vaccines and has raised serious questions regarding the capacity for vaccine-induced polyclonal Abs against the CSP to consistently protect humans. We now report immunization studies with a multiple Ag peptide vaccine designed to rely on "universal" T epitopes from tetanus toxin to produce T cell help for induction of protective Abs against the repeat region of the PyCSP. When delivered with a nonionic block co-polymer adjuvant, the vaccine protected 78 to 100% of three inbred strains of mice, and 100% of outbred mice against P. yoelii sporozoite challenge. Protection was associated with Ab titer, and passive transfer of purified IgG from immune mice protected naive recipients. Similar protection was achieved when the peptide was encapsulated in liposomes with lipid A and mixed with aluminum hydroxide. By demonstrating for the first time solid protection against P. yoelii by polyclonal Abs against the CSP, these data provide the rationale for assessment of a similarly constructed and formulated P. falciparum CSP multiple Ag peptide vaccine in humans. PMID- 7876550 TI - Overexpression of vascular permeability factor (VPF/VEGF) and its endothelial cell receptors in delayed hypersensitivity skin reactions. AB - Delayed hypersensitivity (DH) is a T cell-mediated form of immune response characterized by a predominantly perivascular, mononuclear cell infiltrate. The venules in DH reactions are hyperpermeable to plasma proteins, leading to extravasation of plasma fibrinogen and its extravascular clotting to form a fibrin gel that promotes induration and angiogenesis. The mechanisms responsible for microvascular hyperpermeability in DH are unknown. Recently, a cytokine named vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF) has been implicated in the chronic vascular hyperpermeability and angiogenesis of solid and ascites tumors, healing wounds, rheumatoid arthritis, and psoriasis. These findings suggested that VPF/VEGF might also have a role in the pathogenesis of DH. Two model systems were studied: allergic contact dermatitis to poison ivy in human volunteers and classical tuberculin hypersensitivity in rats. In both, in situ hybridization revealed that the mRNAs encoding VPF/VEGF were strikingly overexpressed in keratinocytes of the epidermis; scattered mononuclear cells infiltrating the dermis also overexpressed VPF/VEGF mRNA, to a greater extent in rat tuberculin than in human contact reactions. In contact reactions, mRNAs for two VPF/VEGF vascular endothelial cell receptors, flt-1 and KDR, were also strikingly overexpressed. Abundant fibrin deposition in both models confirmed that dermal microvessels were indeed hyperpermeable to plasma fibrinogen. These results implicate VPF/VEGF as a potentially important mediator in the pathogenesis of cell-mediated immunity and provide further evidence that products of epithelial cells may regulate the inflammatory response. PMID- 7876551 TI - Evidence for the involvement of arginine 462 and the flanking sequence of human C4 beta-chain in mediating C5 binding to the C4b subcomponent of the classical complement pathway C5 convertase. AB - Replacement of human C4 beta-chain residue arginine 458 by tryptophan, a substitution that occurs naturally in the hemolytically inactive A6 allotype of C4, totally abrogates the molecule's ability to act as a C5 binding subunit of the classical pathway C5 convertase. Hydropathy plots predict R458 to be within a hydrophilic segment extending from residue 455 to 469 and having the sequence SIERPDSRPPRVGDT. To further assess the potential involvement of this segment in the C5 binding function of C4, we have engineered "ala-scan" mutants through this segment, concentrating predominantly on charged residues, and analyzed their functional profiles. C4B isotype mutant proteins S455A (0.7), E457A (1.1), R458A (0.3), D460A (0.2), R462A (0.0), R465A (0.6), and D468A (0.3) displayed the relative to wild-type hemolytic activities indicated in the parentheses. In all cases, the hemolytic defect was accounted for solely at the C5 convertase stage. The total absence of C5 binding activity in the R462A mutant suggests a requirement for the guanidinium group per se, because mutants with a charge conservative lysine or a relatively isosteric methionine at this position were also completely inactive. In contrast, the inactivity of the C4A6-like R458W mutant is probably caused by the intolerance of tryptophan in a hydrophilic segment, as substitution of R458 by alanine or methionine yielded recombinant molecules that retained 30% and 60% of wild-type hemolytic activity, respectively. Taken together, the mutagenesis results strongly imply that residues in the 455-469 segment contribute to the C5 binding site in C4; however, the conformational context of the segment appears to be crucial, as a synthetic peptide corresponding to this segment displayed no ability to inhibit C5 binding to surface-bound C4b. PMID- 7876552 TI - ATP induces the release of IL-1 from LPS-primed cells in vivo. AB - The secretion of IL-1 from murine macrophages in vitro is an inefficient process that is distinct from those of other cytokines such as IL-6. We have therefore studied this process in vivo to see if these differences are maintained. Intraperitoneal injection of LPS in mice induced production and release of IL-6 into the extracellular fluid (peritoneal lavage). Although induction of intracellular IL-1 alpha and IL-1 beta was readily detected, these cytokines were not detected extracellularly. Injection of ATP 2 h after LPS led to the rapid extracellular release of IL-1 beta, IL-1 alpha, lactate dehydrogenase, and beta-N acetylglucosaminidase. Western blot analysis revealed that a large proportion of the IL-1 beta was released as the 17-kDa form, whereas IL-1 alpha was unprocessed. Adenosine 5'-O-(3-thiotriphosphate) was also effective in causing IL 1 release but not UTP or ADP. This suggests that the ATP-mediated release of IL-1 is a receptor-mediated phenomenon that is associated with cell lysis. PMID- 7876553 TI - Identification of complement receptor type 1-related proteins on primate erythrocytes. AB - The purpose of this study was to characterize the structure and function of the immune adherence receptor (CR1, CD35, C3b/C4b receptor) of primates. Western blotting, immunoprecipitation, ELISA, and affinity chromatography with homologous C3b and C4b were utilized. The major cross-reactive E membrane protein of ten species of primates tested was lower in m.w. than was human CR1 and fell into two size groups of 55 to 75 and 130 to 165 kDa. There was 10- to 100-fold more CR1 per primate E than human E. Five species also expressed lesser quantities of a protein similar in m.w. (approximately 200 kDa) to human CR1. In contrast to E, the major cross-reactive protein on PBMC was similar in size to human CR1. Four species also expressed lesser amounts of a lower m.w. protein on their PBMC of the same M(r) as that found on their E. Affinity chromatography demonstrated that the approximately 200-kDa form, if present, was recovered with a similar efficiency to that of human CR1. Three patterns of binding, however, were identified among the lower m.w. proteins: 1) C3b > or = C4b; 2) C4b > C3b; and C3b only or predominantly. The fact that these E proteins cross-react with Ab to human CR1, bind homologous C3b and, in most cases, C4b, and for some species represent the only such protein expressed on their E identifies them as immune adherence receptors. The 70-kDa CR1 of the chimpanzee E seems to arise by alternative splicing of the mRNA encoding the 200-kDa protein. These data raise interesting questions relative to the evolution of CR1 in primates and provide a basis for analysis of structure-function relationships among these size forms of CR1. PMID- 7876554 TI - Class II MHC gene expression in microglia. Regulation by the cytokines IFN-gamma, TNF-alpha, and TGF-beta. AB - The molecular mechanism(s) by which three cytokines (IFN-gamma, TNF-alpha, TGF beta) affect class II MHC gene expression in primary rat microglia was examined. IFN-gamma is a potent inducer of the class II gene, and this induction is unaffected by treatment with either TNF-alpha or TGF-beta. Transient transfection of primary rat microglia with an HLA-DRA promoter linked to the chloramphenicol acetyltransferase reporter gene (DRA-CAT) demonstrated that IFN-gamma acts at the transcriptional level to induce class II MHC gene expression, and that TNF-alpha and TGF-beta have no influence on IFN-gamma-induced promoter activity. Experiments using a series of DRA substitution mutants that individually affect the W, X1, X2, or Y elements, as well as a double mutation in both X1 and X2, indicate that all four of these elements are required for responsiveness of the DRA promoter to IFN-gamma. The effect of IFN-gamma and TNF-alpha on DNA binding proteins by microglia was examined. A constitutive complex with specificity for the X2 box was detected in extracts from unstimulated microglia. IFN-gamma treatment changed this complex to migrate with slower mobility, and TNF-alpha had no effect on either the constitutive or IFN-gamma-induced complexes. These studies provide information on the molecular regulation of the class II MHC gene in microglia, a cell type critically involved in immune regulation within the central nervous system. PMID- 7876555 TI - Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides activate monocytes/macrophages. AB - The observation that the major membrane immunogens of the spirochetal pathogens. Treponema pallidum and Borrelia burgdorferi are lipoproteins prompted studies to investigate macrophage activation by the 47-kDa lipoprotein of T. pallidum and the acylated outer surface protein A (OspA) of B. burgdorferi. Both lipoproteins induced the synthesis of biologically active TNF-alpha and chloramphenicol acetyltransferase in a murine macrophage cell line transfected with a chloramphenicol acetyltransferase reporter gene controlled by a TNF promoter (TB2 cells). Nonacylated forms of these polypeptides did not induce cell activation. Comparison between purified OspA and B. burgdorferi cellular lipids revealed that the former was the more potent inducer of TNF-alpha. Synthetic lipohexapeptides corresponding to the N-termini of the 47-kDa lipoprotein of T. pallidum and OspA also activated TB2 cells in a dose-dependent fashion, whereas the nonlipidated hexapeptides were without effect, further underscoring the importance of protein acylation to cell activation. Among several lines of evidence supporting that macrophage stimulation by LPS and lipopeptides proceeds via different mechanisms, the most notable was that lipopeptides activated peritoneal macrophages from LPS nonresponsive C3H/HeJ mice. The potential for spirochetal lipoproteins to function as general macrophage activators was demonstrated by the ability of the synthetic analogues to induce IL-1 beta, IL-6, and IL-12, in addition to TNF, in murine and/or human macrophages. Our findings indicate that spirochetal lipoproteins may be important immunomodulators in syphilis and Lyme disease and that the synthetic lipopeptides will be useful surrogates for studying immune mechanisms operative in the two spirochetal diseases. PMID- 7876556 TI - Prostaglandin E2 release triggered by phagocytosis of latex particles. A distinct association with prostaglandin synthase isozymes in bone marrow macrophages. AB - Previous studies showed that murine bone marrow-derived macrophages (M phi) induced in vitro by IL-3 express cellular prostaglandin G/H synthase (PGHS)-1 but not PGHS-2. To induce PGHS-2 in this study, the M phi were primed further with IFN-gamma plus LPS. The expression of the PGHS isozymes was determined by cytometric analysis using Abs against PGHS-1 and PGHS-2. The expression of PGHS 2, but not PGHS-1, was dexamethasone-sensitive. To assess PGE2-releasing capacity, the primed M phi were triggered by challenge with calcium ionophore A23187, the protein kinase C (PKC) activator PMA, exogenous arachidonic acid, and 1.1-micron latex bead particles. Our results showed that the primed M phi expressed both isozymes and responded to all challenges used to release a substantial amount of PGE2 (> 10 ng PGE2/10(6) cells/ml), whereas the control unprimed M phi responded to A23187 and arachidonic acid but not to PMA or latex beads to release PGE2. However, the primed M phi did not release PGE2 when triggered with nonphagocytosable particles (> or = 40 microns) or when pretreated with cytochalasin D before they were challenged with 1.1-micron beads. Furthermore, staurosporine, a PKC inhibitor, did not inhibit the PGE2 release triggered by the beads. PMA-triggered PGE2 release by the primed M phi, in sharp contrast, was staurosporine-sensitive but cytochalasin D-resistant. Our data suggest that there are multiple or alternative pathways for triggering PGE2 synthesis and release distinctively associated with two PGH synthase isozymes. It is of special interest that the novel pathway triggered by interiorization of particles is associated with the expression of PGHS-2. PMID- 7876557 TI - CD50 (ICAM-3) is phosphorylated on tyrosine and is associated with tyrosine kinase activity in human neutrophils. AB - CD50 (ICAM-3) is expressed at a high level on resting blood granulocytes, monocytes, and lymphocytes. The constitutive high expression of CD50 on resting leukocytes suggests that it is an important LFA-1 ligand in the initiation of the immune/inflammatory response. Using a radiolabeling technique initially designed to detect ecto-protein kinase activity, we found that CD50 mAbs immunoprecipitated a approximately 125- to 170-kDa phosphoprotein from human neutrophils. Phosphorylation was increased after stimulation with the chemotactic agent FMLP, platelet-activating factor, 12-O-tetradecanoyl-phorbol-13-acetate, and the calcium ionophore A23187. This increase in phosphorylation was transient with the maximal phosphorylation, being observed by 1 min. Phosphoamino acid analysis revealed that CD50 contained predominantly phosphotyrosine. Although this assay system was designed initially to detect ecto-protein kinase activity, subsequent studies have shown that membrane proteins can be phosphorylated on the cytoplasmic domain under these conditions. When CD50 was immunoprecipitated from solubilized neutrophils, protein tyrosine kinase activity associated with CD50 was detected in the immunoprecipitate. The data suggest that phosphorylation of CD50 on tyrosine by an associated tyrosine kinase plays a role in the function of CD50. PMID- 7876558 TI - Both TNF receptors are required for TNF-mediated induction of apoptosis in PC60 cells. AB - A rat/mouse T cell hybridoma (PC60) was transfected either with human (h) TNF-R p55 (TNF-R55), p75 (TNF-R75) or both cDNAs. hTNF-R55 expression was below 50 molecules/cell, whereas the number of hTNF-R75 reached about 4000 molecules/cell. Only cells co-expressing the two types of receptor showed TNF-dependent apoptosis, in contrast to cells expressing similar levels of only one receptor type, indicating that both TNF-R55 and TNF-R75 are required. Stable co transfection of the bcl-2 proto-oncogene largely prevented this TNF-mediated induction of apoptosis. We found that a high level of hTNF-R75 expression was essential for obtaining TNF-dependent apoptosis in PC60 cells in addition to a low number of hTNF-R55. Both receptors are signal transducing because simultaneous triggering of hTNF-R55 and hTNF-R75 by agonistic mAbs or by TNF-R specific TNF muteins induced similar levels of apoptosis as wild-type hTNF. Apoptotic killing of only those lymphocytes expressing a high, induced level of TNF-R75, in addition to TNF-R55, may play a physiologically important role. PMID- 7876559 TI - Expression of TNF receptors by T cells and membrane TNF-alpha by alveolar macrophages suggests a role for TNF-alpha in the regulation of the local immune responses in the lung of HIV-1-infected patients. AB - High amounts of TNF-alpha are released by alveolar macrophages (AMs) in the lungs of patients with HIV-1 infection. To investigate the role of this cytokine in the local immune response, we studied the expression of surface receptors for TNF alpha (TNF-Rs) and the presence of the transmembrane form of TNF-alpha (mTNF alpha) on bronchoalveolar lavage (BAL) cells recovered from 14 patients with HIV 1 infection. The role of TNF-alpha both in the events leading to the T cell alveolitis and as a mediator of cytotoxicity was also evaluated. TNF-R expression was determined by flow cytometry on BAL CD8 lymphocytes and AMs (i.e., the cells that account for the alveolitis in HIV-1 infection). We found that CD8 cells express the 75-kDa (CD120a) but not the 55-kDa (CD120a) TNF-Rs, whereas AMs were devoid of TNF-R expression. More than 90% of BAL T cells efficiently bound TNF alpha; when T cells were tested for their proliferative capacity, an up regulation of the IL-2-mediated proliferation by TNF-alpha was observed, suggesting that this cytokine may drive the in situ proliferation of CD120b+ T cells. As shown by flow cytometry analysis and immunoprecipitation with anti-TNF alpha Ab, mTNF-alpha expression was observed on AMs but not on alveolar T cells. Fixed AMs showed high levels of killing against TNF-sensitive targets. Taken together, our data demonstrate the selective expression of TNF-Rs and mTNF-alpha on cells accumulating within the alveolar spaces of patients with HIV-1 infection, pointing to the compound role of TNF-alpha in the local immune responses. PMID- 7876560 TI - A 12-kDa protein of Mycobacterium tuberculosis protects mice against experimental autoimmune encephalomyelitis. Protection in the absence of shared T cell epitopes with encephalitogenic proteins. AB - Mycobacterium tuberculosis (Mt), routinely used to promote the induction of autoimmune diseases, can also protect against their development. Recently, we demonstrated that purified protein derivative (PPD) is the major fraction of Mt that protects mice against the induction of experimental autoimmune encephalomyelitis (EAE). We have now ascribed the protective activity to a 12-kDa protein purified from PPD. Sequence identity between the first 17 amino acids of the 12-kDa PPD protein and the 10-kDa BCG-a protein of Mt suggested that these proteins are identical or closely related. However, in contrast to the 12-kDa PPD protein, the 10-kDa BCG-a protein did not protect against EAE, nor did it stimulate PPD-specific T cells, suggesting that the 12-kDa PPD protein and the 10 kDa BCG-a protein share some homology but are not identical. The protective activity of the 12-kDa PPD protein correlated with its ability to stimulate PPD specific T cells. The significance of this correlation is not clear and the mechanism of protection was not fully elucidated. However, N-terminal sequence identity between the 12-kDa PPD protein and the 10-kDa BCG-a protein, which shares 43% homology with GroES stress protein, suggested that the 12-kDa PPD protein may also belong to the bacterial heat-shock protein (hsp) family. Thus, by analogy with protection against arthritis or diabetes by hsp65, the mechanism of protection could be based on shared T cell epitopes with the target self Ag. However, the 12-kDa PPD protein did not stimulate encephalitogenic T lymphocytes. Effective protection against EAE by the 12-kDa PPD protein, in the absence of a stimulatory effect on encephalitogenic T lymphocytes, suggests a potential use for this protein in the therapy of autoimmune diseases. PMID- 7876561 TI - Anti-TNF-alpha treatment down-regulates the expression of fibronectin and decreases cellular infiltration of cardiac allografts in rats. AB - Extracellular matrix (ECM) components provide costimulatory signals for T cell activation in vitro, and may be critical for lymphocyte migration and tissue positioning in vivo. We conducted a series of studies in rat recipients of cardiac allografts to evaluate intragraft expression of a prominent ECM protein, fibronectin (FN), and to analyze the effects of infusing a neutralizing anti-TNF alpha serum on FN expression and lymphocyte migration into the transplants. LBNF1 cardiac allografts were rejected within 8 days in control LEW rats. A prominent immunohistochemical feature of this immune response was the dense deposition of FN at the graft site as early as 3 h, which then peaked at 4 to 6 days. The early 3-h FN deposition (likely plasma FN) was noted before cellular infiltration. Northern blot analysis established that a marked induction of FN mRNA expression occurred in rejecting cardiac allografts at day 4 after transplantation. To determine the source of FN mRNA, we conducted a series of in situ hybridization studies with probes for FN and lysozyme, a macrophage-specific marker. Indeed, the majority of graft-infiltrating cells expressed lysozyme mRNA and FN mRNA. Administration of anti-TNF-alpha serum into LEW hosts (0.5 ml i.v. at days 1 and 3 only) abrogated acute rejection and prolonged cardiac allograft survival to approximately 13 days. This was accompanied by depressed circulating and intragraft TNF-alpha levels, and markedly down-regulated FN mRNA/protein expression patterns, as compared with those in recipients given nonimmune rabbit serum. Anti-TNF-alpha treatment also markedly decreased graft infiltration by ED1+ monocytes/macrophages, OX-8+, and VLA-4+ cells, normally peaking at 4 days. Moreover, we found that the migration of 111In-labeled specifically sensitized lymph node lymphocytes to cardiac allografts in secondary rat recipients conditioned with anti-TNF-alpha serum was significantly decreased, as compared with that in controls. Thus, FN expression by intragraft macrophages occurs within the same interval as cellular infiltration, and may act as an ECM component "signal" for selective homing of recirculating lymphocytes in graft recipients. The results of this study support the notion that in vivo interactions between mononuclear cells and ECM may be vital for the ingress of alloreactive lymphocytes at the graft site, and offer potential novel sites for therapeutic intervention in the control of transplant rejection. PMID- 7876562 TI - HIV-1 down-regulates CD4 costimulation of TCR/CD3-directed tyrosine phosphorylation through CD4/p56lck dissociation. AB - One consequence of HIV type 1 (HIV-1) infection is the gradual loss of responsiveness of T lymphocytes to Ags both in vitro and in vivo. It has been suggested that the underlying mechanism that contributes to this T cell dysfunction before CD4+ cell decline involves down-regulation of surface receptors, alterations in intracellular redox status, interference by viral Ags, and later in infection, the absence or alteration of specific cytokine production. In this report, we demonstrate that infection of the T-lymphocytic cell line H9 with the LAI isolate of HIV-1 results in profoundly altered regulation of CD4-induced costimulation of TCR/CD3-directed signaling. TCR/CD3 induced tyrosine phosphorylation of the intracellular enzyme phospholipase-C gamma 1 and the surface receptor/substrates CD5 and CD6 was unaffected by virus infection, whereas augmented responses normally observed after the co-ligation of CD4 with TCR/CD3 on T lymphocytes were absent in HIV-1-infected H9 cells. Costimulation of TCR/CD3-induced signaling via MHC class II molecules was also down-regulated in virally infected cells. TCR/CD3 and HLA-DR receptor expression remained intact in infected cultures for at least 3 wk, whereas CD4 surface expression was gradually lost but maintained for up to 1 wk, suggesting that the absence of costimulation early in infection was not surface receptor density dependent. In HIV-1-infected cells, CD4 was not physically linked with its associated tyrosine kinase p56lck, whereas normal levels of p56lck were readily recovered from the cellular cytoplasm. Similar observations were noted in cultures of H9 cells infected with a field isolate of HIV-1 obtained from cultured PBMC from an infected donor. HIV-1 infection of T lymphocytes thus down regulates potentially critical early signal transduction events by a mechanism that appears to involve interference of CD4 receptor association with p56lck. A potential outcome of these biochemical effects may include the limited responsiveness of infected T cells to antigenic stimulation observed during HIV-1 infection. PMID- 7876563 TI - Correction of proliferative responses in purine nucleoside phosphorylase (PNP) deficient T lymphocytes by retroviral-mediated PNP gene transfer and expression. AB - Purine nucleoside phosphorylase (PNP; EC 2.4.2.1) deficiency is associated with a fatal T cell immunodeficiency in children, a candidate condition for gene therapy by introduction of functional PNP sequences into either T lymphocytes or more primitive progenitor cells in the bone marrow. To test the effectiveness of PNP gene transfer in T lymphocytes, a retroviral vector (LmPSN-2) was designed and constructed to express the murine PNP cDNA under transcriptional regulation of the Moloney murine leukemia virus long terminal repeat. LmPSN-2 was first used to mediate gene transfer and expression of electrophoretically distinct murine PNP in normal (PNP-positive) human PBL. Peripheral blood leukocytes were then obtained from a PNP deficient patient and characterized phenotypically. Despite their paucity and general mitogenic unresponsiveness, T lymphocytes from this patient were successfully grown in culture by using anti-CD3 with rIL-2 and then transduced with LmPSN-2. Elevated PNP enzyme activity was observed in the transduced cell population. Mitogenic and allogeneic responses, normally depressed in PNP-deficient patients' cells, were partially corrected in the transduced cell population relative to nontransduced cells. These results suggest the possibility of effecting improved immunologic function in PNP-deficient T lymphoid cells by retroviral-mediated gene transfer as therapy for PNP deficiency. PMID- 7876564 TI - Existence of a soluble form of CD50 (intercellular adhesion molecule-3) produced upon human lymphocyte activation. Present in normal human serum and levels are increased in the serum of systemic lupus erythematosus patients. AB - CD50 (ICAM-3) is a leukocyte differentiation Ag expressed almost exclusively on hemopoietic cells, with a key role in the first steps of immune response. To develop a specific sandwich ELISA to detect a soluble CD50 form (sCD50), two different mAbs (140-11 and 101-1D2) recognizing non-overlapping epitopes were used. sCD50 was detected in the supernatant of stimulated PBMCs, with the highest levels after CD3 triggering. Simultaneously, the CD50 surface expression diminished during the first 24 h. sCD50 isolated from culture supernatant and analyzed by immunoblotting showed an apparent m.w. of 95 kDa, slightly smaller than the membrane form. These data, together with Northern blot kinetics analysis, suggest that sCD50 is cleaved from cell membrane. Furthermore, we detect sCD50 in normal human sera and higher levels in sera of systemic lupus erythematosus (SLE) patients, especially in those in active phase. The sCD50 levels showed a positive correlation with sCD27 levels (r = 0.4213; p = 0.0026). Detection of sCD50, both after in vitro CD3 triggering of PBMCs and increased in SLE sera, suggests that sCD50 could be used as a marker of lymphocyte stimulation. PMID- 7876565 TI - Purification of immunoglobulin E (IgE) antibodies from sera with high IgE titers. AB - A three stage method for the ultrapurification of polyclonal IgE from human serum is reported using anion exchange chromatography followed by monoclonal antibody based positive and negative affinity chromatography. Following dialysis of 25-100 ml of serum (2.3-14 micrograms IgE/ml, n = 4) against 0.05 M Tris pH 8, each specimen was subjected to diethylaminoethyl (DEAE)-cellulose chromatography (serum/matrix = 1/4). IgE was eluted with 0.05 M Tris, 0.05 M NaCl pH 8, yielding an IgE recovery of 61-93%, with removal of approximately 90% of other serum proteins and an IgE purity ([IgE]/[Igs]) of 0.1-1.1%. After adjusting to 0.1 M NaCl and concentrating approximately 30-fold, the eluted IgE was further purified by affinity chromatography using a panel of IUIS/WHO-documented mouse monoclonal anti-human immunoglobulin antibodies (alpha hIg-MAbs). First, the IgE-enriched DEAE-cellulose chromatography fraction was incubated in a batch mode with two alpha hIgE-Fc MAbs (HP6029, HP6061) coupled to CNBr-Sepharose, CL-4B. IgE was eluted with 0.05 M glycine pH 2.8 and immediately neutralized. The IgE recovery was 32-52% and IgE purity was 72-97%. Silver-stained SDS-PAGE and noncompetitive solid-phase two-site immunoenzymetric assays for total human IgA, IgE, IgG and IgM indicated that IgA, IgG and IgM were the only contaminants. Next, the IgE was concentrated 10-30-fold in the presence of 0.1% HSA. One IgE specimen was ultrapurified in a batch mode by negative selection chromatography using three pairs of alpha hIg-MAbs (alpha hIgA: HP6111 + HP6123; alpha hIgG: HP6017 + HP6046; alpha hIgM: HP6081 + HP6083) coupled to CNBr-Sepharose, CL-4B. IgE purity increased from 91% to > 99.9% with approximately 70% recovery of IgE for this step. The ultrapurified IgE antibody was shown to be functionally reactive for allergen and Fc epsilon RI receptors on human basophils. We conclude that alpha hIg-MAbs are powerful tools to facilitate the affinity purification of functionally active human IgE from serum; however, when the analyte is present in low concentration, a carrier protein needs to be added to minimize non-specific loss of the material during this process. PMID- 7876566 TI - Monoclonal antibodies against a minor and the major coat proteins of filamentous phage M13: their application in phage display. AB - We have produced monoclonal antibodies (MAbs) which react with a minor and the major coat proteins of filamentous phage M13 and have characterised them by combining the techniques of enzyme-linked immunosorbent assay (ELISA) and Western blotting. These coat proteins are the minor coat protein, gIIIp, the product of gene III and the major coat protein, gVIIIp, the product of gene VIII. Both gIIIp and gVIIIp are important in the context of 'phage display' of foreign peptides/proteins as fusions to these proteins. The anti-gIIIp MAbs were able to detect native gIIIp as well as the fusion proteins comprising foreign proteins and gIIIp in ELISA and on Western blot, indicating their utility for studying the expression of foreign proteins in phage display. Similarly anti-gVIIIp MAbs detected gVIIIp both in ELISA and on Western blot. In an 'affinity capture phage ELISA', phages that were captured by virtue of the interaction between the foreign protein (ligand fused to the gIIIp and displayed on the phage surface) and the immobilised counterpart (receptor), could be easily detected using anti gVIIIp MAbs. Considering the potential of 'phage display' technology in protein engineering, these antibodies should find wide applications. PMID- 7876567 TI - Autoantibodies directed against ribosomal P proteins: use of a multiple antigen peptide as the coating agent in ELISA. AB - Autoantibodies directed against the ribosomal proteins P0, P1 and P2 (P proteins) are specific for systemic lupus erythematosus (SLE) and there are some evidences that they could be related to the neuropsychiatric manifestations of the disease. In this study, a multiple antigen peptide (MAP) carrying four copies of the C terminal peptide (13 residues) of the P2 protein, which is a common epitope of the three P proteins, was prepared for use in an ELISA assay. It was employed to detect antibodies directed against the ribosomal P proteins in 102 SLE patients and the results were compared with those obtained using immunoblotting (IB). With this new ELISA, antiribosomal P protein antibodies were found in 15/102 SLE sera. These results correlated well with the results of IB. Furthermore, we confirmed that naturally occurring antiribosomal P protein antibodies are directed mainly against the epitope containing the C-terminal sequence and shared by the three P proteins. MAP appears to be an excellent coating agent for ELISA assays designed to detect anti-P antibodies. Further experiments showed the superiority of MAP, compared to the free peptide, in the detection of weakly positive sera. This ELISA can also be used for the serological follow-up of SLE patients. PMID- 7876568 TI - Amino acid sequence based PCR primers for amplification of rearranged human heavy and light chain immunoglobulin variable region genes. AB - Previously described primers for PCR amplification of variable immunoglobulin (Ig) genes were based on gene sequences. To include the large number of amino acid sequences of antibodies whose DNA has not been sequenced and to ensure a maximal fit to rearranged human Ig variable region genes, we have made a comprehensive comparison of both protein and nucleotide sequences. The resulting set of 15 primers was able to amplify a wide range of rearranged antibody variable region genes. Restriction sites included in the primers facilitate cloning of the PCR products into various expression vectors. Sequence analyses of PCR-amplified cDNA derived from a polyclonal B cell population showed that maximal enrichment is obtained for highly represented variable Ig gene subgroups. Rarely occurring V kappa 4 and V lambda 5 subgroups were not detected. Rearranged Ig variable region genes from each of 19 human B cell lines were also amplified. Comparisons to germline sequences allowed the allocation of rearranged genes to the original Ig genes. This primer set should be very useful for generating large repertoires of rearranged V genes and for amplifying genes of individual B cell clones. PMID- 7876569 TI - A new method for phenotyping proliferating cell nuclear antigen positive cells using flow cytometry: implications for analysis of the immune response in vivo. AB - The incorporation of radioactive nucleotides into newly synthesized DNA has been established as a standard method for the detection of proliferation in eucaryotic cells. Unfortunately the use of this method makes it harder to obtain information on the phenotype of proliferating cells in mixed cell populations. For this reason we established a flow-cytometric approach employing a monoclonal antibody specific for murine as well as human proliferating cell nuclear antigen (PCNA) and a double labeling technique for detection of cell membrane-expressed phenotypic markers. The efficiency of this immunostaining procedure was confirmed by simultaneous and highly specific detection of PCNA in nuclear structures as well as cell membrane-expressed antigens using cytological techniques. In vitro experiments with mitogen- and alloantigen-stimulated murine lymph node cells (LNC) and human peripheral blood mononuclear leukocytes (PBML) revealed a good correlation of total [3H]thymidine incorporation into DNA and expression of PCNA. For the analysis of proliferating cells activated in vivo the method was employed to evaluate the local lymph node assay which assesses the allergenicity of small chemicals. LNC prepared from the cervical lymph nodes of mice treated on 4 consecutive days with sensitizing concentrations of the contact allergens oxazolone, TNCB and DNFB as well as the irritants benzoic acid and SLS in comparison to the solvent control showed a dramatic increase in the total amount of proliferating cells for contact allergen-treated animals in comparison to the solvent control and irritant-treated mice. In addition a detailed phenotyping of the proliferating cell populations was possible. This approach offers an easy to perform, non-radioactive method for the assessment of proliferation of murine as well as human leukocytes in vitro and especially in vivo and will be of great advantage for situations where the phenotype of proliferating cellular subsets in heterogeneous populations is of interest. PMID- 7876570 TI - Fluorescence labelling with europium chelate of beta-diketones and application in time-resolved fluoroimmunoassays (TR-FIA). AB - Five beta-diketone derivatives were studied for multiple labelling of proteins. The labelled proteins were characterized by absorption and fluorescence measurements. It was found that proteins labelled with chlorosulfonyl thenoyltrifluoroacetone (CTTA) were able to form highly fluorescent complexes with Eu3+ which exhibited prolonged fluorescence whereas the Eu3+ complex of hydrolyzed CTTA exhibited almost no fluorescence, and so unreacted ligand gave no background signal in immunoassays even if it was not removed from the labelled reagent. The effect of labelling on the biological activity of albumin and polyclonal antibody was studied and it was also shown that the new probe could be used in time-resolved fluorescence immunoassays. PMID- 7876571 TI - Stabilization of erythrocytes by aldehydes and suitability of chicken IgY for the detection of potato virus X (PVX) in avidin-biotin enhanced reverse passive haemagglutination. AB - Methods are described for the detection of potato virus X (PVX) by reverse passive haemagglutination (RPH) by means of polyclonal antiviral antibodies coupled to sheep red blood cells (sRBC) and the chromic chloride method. The cells were stabilized with pyruvic aldehyde, thus providing a stock suspension for numerous coupling experiments lasting several months. Anti-PVX IgY, which is readily isolated in large amounts from the egg yolk of immunized chickens, was used in an avidin-biotin enhanced RPH assay with stabilized sRBC. With this method the PVX detection rate achieved was comparable to that of RPH assays using fresh non-fixed sRBC. In addition, avidin-coated sRBC could be stored for weeks at 4 degrees C and subsequently used for coupling with biotinylated IgY. PMID- 7876572 TI - Transient transfection of murine B lymphocyte blasts as a method for examining gene regulation in primary B cells. AB - Studies of the biochemical and genetic processes associated with activation of B lymphocytes have contributed much to the understanding of the regulation of the B cell response to antigen. Primary, non-transformed B cells from the spleen in mice and the tonsils or peripheral blood in humans have proven to be informative models for dissection of the biochemical events leading to B cell activation. In contrast, genetic studies of this process have relied on transformed cell lines grown in culture. The influence of the transformed state on the results obtained using these models may limit their physiological relevance. This report describes a method whereby non-transformed B lymphocytes in primary culture can be transfected for use in studies of gene regulation in response to antigen receptor signals. Transfection was accomplished after only a 72 h exposure to LPS. The cells obtained after LPS treatment were greater than 97% pure, and more importantly, remained responsive to antigen-receptor generated signals. Responsiveness was confirmed by demonstrating induction of mRNA for the primary response gene egr-1, as well as induction of specific transcription factor binding activity in nuclear extracts from these cells. DEAE-dextran-mediated transient transfection was utilized to introduce an egr-1 promoter/reporter construct into these cells. This analysis of promoter activity yielded results which were indistinguishable from the pattern of expression of the endogenous egr 1 gene. Potential applications for dissection of transcriptional regulatory pathways in B lymphocytes are discussed. PMID- 7876573 TI - Inverse PCR amplification of rare T cell receptor delta messages from mucosal biopsy specimens. AB - Reverse transcription (RT) PCR is an important tool in studies of the repertoire of T cell antigen receptors (TCR). In combination with inverse PCR, it can be used to amplify TCR transcripts whose V regions are unknown. Little is currently known regarding the delta TCR repertoire in human intestine. Here, RT inverse PCR was adapted to efficiently amplify low abundance delta TCR sequences from human colonic mucosal biopsy specimens. In this protocol, high yields of PCR products were obtained by optimizing the conditions at which cDNA autoligation was performed. PMID- 7876574 TI - In vitro immunization: generation of neutralizing monoclonal antibodies to human interleukin-10. AB - The potential of the in vitro immunization technique to evoke an immune response against an immunomodulatory protein was evaluated using, as antigen, human interleukin-10 (IL-10), a novel cytokine with pleiotropic effects on human and murine lymphocytes and macrophages. After pre-priming the support cells for 48 h and subsequent 3-day stimulation of splenocytes from a non-immune BALB/c mouse with recombinant human IL-10 (rhIL-10; 2 micrograms/ml), significant stimulation of splenocytes was observed. 7 days after fusion with the non-secreting myeloma line X63/Ag8.653, IL-10-specific antibodies were detected by ELISA and dot blot in more than 70% of the hybridoma supernatants. After limiting dilution of the hybridoma cells showing IL-10-neutralizing activity in a bioassay using murine MC/9 mast cells, the isotype of the monoclonal antibodies (mAbs) obtained was 20% IgM, 16% IgG and 6% IgA. All other antibodies elicited IgM as well as IgG isotypes. The neutralizing activity of the specific mAbs tested was dose dependent. Our results show that in vitro immunization can be employed successfully to generate functional mAbs to immunomodulatory proteins, even if these exhibit cross-species activity. PMID- 7876576 TI - Breast feeding with love. PMID- 7876575 TI - ELISA for titration of antibodies to tetanus toxoid in sera of immunized guinea pigs as an alternative to the toxin neutralization test in mice. PMID- 7876578 TI - Prolactin levels in infertility and bromocriptine therapy in hyperprolactinaemia. AB - Serum prolactin levels were estimated in 100 infertile patients along with the other investigations for infertility. Hyperprolactinaemia was noted in 41% of the infertile patients. Prevalence of hyperprolactinaemia was greater in patients with ovulatory cycles ie, 55% compared to 31.66% in patients with anovulatory and oligo-ovulatory cycles. Fifty per cent of the patients with regular menses had hyperprolactinaemia. Conception occurred in 9 out of 18 hyperprolactinaemic infertile patients (a pregnancy rate of 50%) treated with bromocriptine. Eleven patients (group 1) were treated with bromocriptine from day 5 to day 30 throughout the menstrual cycle and 5 conceptions occurred. Six patients (group 2) with ovulatory cycles were treated with bromocriptine during the luteal phase, from the day of ovulation till next menses and 4 conceived. One patient of prolactinoma treated with bromocriptine failed to conceive. Bromocriptine therapy restricted to the luteal phase in ovulatory patients has yielded successful results. Based on these observations it is suggested that all patients of infertility need serum prolactin estimation. PMID- 7876577 TI - Complications of percutaneous renal biopsy. AB - Three hundred twenty renal biopsies were done in 305 patients over a period of 5 years. Adequate tissue for pathologic diagnosis was obtained in about 79% of biopsy attempts. The overall morbidity of procedure was 6.8%. Haematuria in 11.8% cases was the commonest complication. Haematuria resolved spontaneously in 63.8% of patients within 4-12 hours. Hypotension due to blood loss occurred in 3 patients (0.98%) who required blood transfusion. Five patients (1.6%) developed perirenal haematoma. Urinary retention requiring single catheterisation was seen in 12 cases (3.9%). Perirenal abscess occurred in one case. Minor complications improving with symptomatic medication included vomiting, abdominal pain and vasovagal attack in 3.6%, 2.6% and 1.6% cases respectively. PMID- 7876579 TI - Incidence of malignancy in Bankura (a retrospective study). AB - A retrospective study on pattern of malignant lesions in a rural district of West Bengal from 1981-1990 was conducted in the department of pathology, BS Medical College, Bankura, West Bengal. A total number of 17,130 cases were received out of which 1976 were malignant lesions (11.53%). The peak incidence of cancer in both sexes was found between the 4th, 5th and 6th decades, ie, 31-60 years of age. Sex-wise distribution showed more incidence in female (1246-62.17%) than in male (730-37.83%). Cancer of the cervix (35.62%) showed the highest incidence in this series. Cancer of the larynx (11.94%) was the commonest cancer in males. Malignancy of the lymph node was observed in 11.43% cases. Malignancy of the lungs and vagina (< 0.5%) showed very low incidence. PMID- 7876580 TI - Aphthous ulcer. PMID- 7876581 TI - Chronic non-specific sclerosing osteomyelitis of clavicle. PMID- 7876582 TI - Gonadectomy in testicular feminisation syndrome. PMID- 7876583 TI - A case of coarctation of aorta in pregnancy. PMID- 7876584 TI - Symmetrical peripheral gangrene. PMID- 7876585 TI - Foetal dystocia--a clinical enigma. PMID- 7876587 TI - Judgement of Supreme Court regarding admissions to medical and engineering college--its implementation. PMID- 7876586 TI - Doctor-patient relationship in a multicultural society. PMID- 7876588 TI - Judgment of Supreme Court regarding admissions to medical and engineering college -its implementation. PMID- 7876589 TI - Late sequelae of ARV--sterile suppuration. PMID- 7876590 TI - RAPD-PCR for identification of Zoophthora radicans isolates in biological control of the potato leafhopper. AB - Biological control studies require the ability to distinguish released pathogens from locally occurring isolates of the same species. We have developed a technique that differentiates genotypes using random amplified polymorphic DNA (RAPD) for the apomictic species Zoophthora radicans (Zygomycota: Entomophthorales), a pathogen of the potato leafhopper, Empoasca fabae (Homoptera: Cicadellidae). RAPD analysis was performed on Z. radicans isolates released in test plots in 1990 and 1991 for leafhopper control; isolates later recovered from the same plots and diverse other isolates were included in the analysis. RAPD fragment profiles of five recovered isolates proved very similar to those of the released isolates and different from all other isolates tested; they are probable descendants of the released isolates. One of the recovered isolates had RAPD profiles similar to isolates derived from aphids and probably represents a population endemic at the release site. In addition to verifying the successful establishment of our experimental releases, RAPD analysis revealed clear relationships among isolates derived from the same host taxon. We propose that this simple and relatively inexpensive method will be valuable in determining the establishment and spread of organisms released in biological control studies. PMID- 7876591 TI - Purification and partial characterization of an induced antibacterial protein in the silkworm, Bombyx mori. AB - Injection of live Escherichia coli into larvae of the silkworm, Bombyx mori, induces antibacterial activity in the hemolymph. The major induced antibacterial activity was purified in two steps by CM-Sephadex C-50 and Sephadex G-100 column chromatography. After trypsin treatment, the purified antibacterial protein lost its activity and the antibacterial activity was found to be partially heat labile. The purified protein was a single polypeptide chain of molecular weight 16 kDa. The 20 N-terminal amino acid sequence of the protein was determined and this sequence showed homology with the N-terminal amino acid sequence of lysozymes reported in other species. The purified protein was found to have comparable antibacterial activity against both E. coli and Micrococcus luteus. The purification of antibacterial protein and the antibacterial properties of the purified protein are discussed. PMID- 7876592 TI - Interaction of the insecticidal crystal protein CryIA from Bacillus thuringiensis with amino acid transport into brush border membranes from Bombyx mori larval midgut. AB - The activities of three related Bacillus thuringiensis delta-endotoxins, designated CryIA(a), CryIA(b), and CryIA(c), as inhibitors of K(+)-dependent amino acid transport into membrane vesicles prepared from the anterior and posterior portions of Bombyx mori larval midgut were measured. Under experimental conditions similar to those occurring in vivo (membrane potential approximately 100 mV, inside negative; pH 7.2in/8.8out; an inwardly directed K+ gradient) CryIA(a) toxin produced a clear dose-dependent inhibitory effect on leucine uptake by both the anterior and the posterior gut membrane vesicles, giving half maximal inhibition constants (IC50) of 2.6 +/- 0.3 and 2.1 +/- 0.2 microgram toxin/mg membrane protein, respectively. The other two delta-endotoxins were practically inactive. A dose-dependent inhibition of amino acid transport by CryIA(a) toxin was also observed on the carrier-mediated K(+)-independent component, i.e., the leucine-only form. This result strongly indicates that the activity of the K+/amino acid cotransporter is directly affected after binding of delta-endotoxin to the brush border membrane. When the extravesicular pH was lowered to pH 7.2, the interaction of CryIA(a) toxin with the brush border appeared more complex, as suggested by the Hill coefficient of the dose-response curves higher than 1. In conclusion, our data indicate that (i) CryIA(a) toxin specifically inhibited K+/leucine symport along the length of the midgut; (ii) the interaction between cotransporters and toxin is affected by the pH of the medium; and (iii) the K+/leucine cotransporter or a strictly associated protein may serve as membrane receptor for CryIA(a) delta-endotoxin in the B. mori larval midgut. PMID- 7876593 TI - Germination of Bacillus thuringiensis spores in bacteriophagous nematodes (Nematoda: Rhabditida). AB - During screening of Bacillus thuringiensis isolates for nematicidal activity it was observed that spores of B. thuringiensis germinated in the intestine of bacteriophagous nematodes in the presence of antibiotics. This phenomenon was studied more closely by scanning electron microscopy. The nematodes were fed with bacterial spore-crystal mixtures in axenic culture medium supplemented with tetracyclin and chloramphenicol. Germination of spores was rare but was more frequently observed in Panagrellus redivivus than in other nematode species investigated. Germination of spores in the nematode intestine resulted in the colonization of the entire nematode within 24 hr. Crude nematode tissue preparations supported germination and subsequent growth of B. thuringiensis spores and vegetative cells. The mechanism for the loss of antibiotic activity in the nematode intestine is unknown. Since B. thuringiensis requires a nutrient rich environment for reproduction, e.g., a cadaver, bacteriophagous nematodes may serve as suitable hosts for B. thuringiensis. PMID- 7876594 TI - A baculovirus polyhedrin gene introduced into stably transformed cells is not expressed effectively. PMID- 7876595 TI - Determination of PCR conditions for RAPD analysis in entomopathogenic nematodes (Rhabditida: Heterorhabditidae and Steinernematidae). PMID- 7876596 TI - Reducing T cell activation as a therapy for human immunodeficiency virus infection. PMID- 7876597 TI - Sustained increases in CD4 cell counts in asymptomatic human immunodeficiency virus type 1-seropositive patients treated with prednisolone for 1 year. AB - Forty-four asymptomatic patients infected with human immunodeficiency virus type 1 (HIV-1), who had 200-799 CD4 cells/microL, received oral prednisolone (0.5 mg/kg for 6 months; 0.3 mg/kg thereafter). After 1 year of treatment, no major side effect or AIDS events had occurred. The percentage of DR+ and CD25+ phenotypes in CD4 T cells decreased significantly as did levels of serum IgG, IgA, and beta 2-microglobulin. Serum p24 antigen and HIV RNA levels remained stable. CD4 cell counts increased significantly at all time points (median increase at 1 year, 119 cells/microL). Peripheral blood mononuclear cell apoptosis after overnight stimulation with anti-CD3 monoclonal antibodies was strongly inhibited at all times. In asymptomatic seropositive patients, immunotherapy for 1 year with glucocorticoids was safe and led to sustained increases in CD4 cell counts and to improvement or stabilization of other biologic markers of disease activity. PMID- 7876598 TI - T cell function in vitro is an independent progression marker for AIDS in human immunodeficiency virus-infected asymptomatic subjects. AB - The predictive value of low T cell reactivity to CD3 monoclonal antibodies for development of AIDS was evaluated and compared with low CD4+ cell numbers and the presence of syncytium-inducing human immunodeficiency virus (HIV) variants in 122 seropositive asymptomatic homosexual men for 4.5 years. Low T cell reactivity was a strong predictor for progression to AIDS in a multivariate proportional hazards analysis using these markers as covariates at entry and as time-dependent covariates. The combination of the three markers was associated with development of AIDS in 6 of 7 men within 15 months. In contrast, the group that lacked any of these markers had a very low risk (11%) for developing AIDS. In groups with one or two of these three markers, progression rates were 33% and 66%, respectively. These data demonstrate that measurement of T cell function in vitro is of value for staging of HIV infection and may be useful for monitoring therapy. PMID- 7876599 TI - Reduction of the in vitro activity of A77003, an inhibitor of human immunodeficiency virus protease, by human serum alpha 1 acid glycoprotein. AB - Since plasma protein binding of antiinfectives can adversely affect drug activity, the effect of serum proteins on the in vitro antiviral activity of A77003, a human immunodeficiency virus type 1 (HIV) protease inhibitor, was investigated. In vitro, A77003 is effective in both acute and chronic infection in 10% fetal bovine or human serum. As the concentration of human serum was increased to 50%, antiviral efficacy decreased 3- to 6-fold. Purified human alpha 1 acid glycoprotein (alpha 1-AGP) at physiologic concentrations (0.5-2 mg/mL) dose-dependently reduced the antiviral activity of A77003. alpha 1-AGP at 1 mg/mL also antagonized the anti-HIV activity of A77003-zidovudine combinations. Therefore, higher concentrations of HIV protease inhibitors than would be predicted, on the basis of in vitro activity in the absence of physiologic concentrations of binding protein, may be required to effectively limit viral replication in vivo. PMID- 7876600 TI - Chronic bacterial enteropathy in patients with AIDS. AB - Enteric infection with adherent bacteria has been seen in a person with chronic diarrhea who was infected with the human immunodeficiency virus. In this study, adherent bacteria were seen in 17% of all patients with AIDS evaluated during a 1 year period. The infection was centered in the cecum and right colon. Three distinct histopathologic patterns of adherence were observed: attaching and effacing lesions, bacteria intercalated between microvilli, and aggregates of bacteria more loosely attached to the damaged epithelium. The infections were associated with weight loss (P < .005) and peripheral blood CD4+ cell of counts < 100/mm3 (P < .05). Eight of 9 patients treated with antibiotics had symptomatic improvement. Bacterial cultures of rectal biopsies frozen at endoscopy yielded Escherichia coli in 12 of 18 cases; aggregative adherence was seen in 6. Isolates from 2 cases hybridized with a DNA probe encoding aggregative properties. These results suggest that chronic infection with adherent bacteria may produce a syndrome of AIDS-associated diarrhea and wasting. PMID- 7876601 TI - Incidence of human T lymphotropic virus type I seroconversion after age 40 among Japanese residents in an area where the virus is endemic. AB - To clarify how seroconversion after age 40 years contributes to the seroprevalence of human T lymphotropic virus type I (HTLV-I), Japanese residents were studied in an area of Kyushu in which HTLV-I is endemic. Cross-sectional data showed higher seroprevalences among subjects > or = 40 than in those < 40 years old (27.0% vs. 7.9%). The prevalence was also greater in women than men (25.5% vs. 17.6%). Six hundred subjects > or = 40 years old were tested during 1976-1993. Among 8 who seroconverted, 5 had an HTLV-seropositive spouse and 2 seroconverted after blood transfusions. The incidences per 1000 person-years of seroconversion in age groups 40-49, 50-59, and > or = 60 years were, respectively, 0.0, 0.0, and 3.3 (range, 1.38-5.13) in men and 0.0, 5.3 (range, 0.11-7.99), and 1.4 (range, 0.00-1.60) in women. The seroconversion incidence was insufficient to account for the rise of seroprevalence in those > or = 40 years old, especially among women. These results suggest that the high rate and sex discordance in HTLV-I seroprevalence after age 40 may depend mainly on the birth cohort effect for vertical or horizontal transmission. PMID- 7876602 TI - Viral shedding and fecal IgA response after Norwalk virus infection. AB - Protection is not conferred by preexposure to Norwalk virus (NV). By use of an ELISA with baculovirus-expressed recombinant NV (rNV) capsid protein, the pattern of NV fecal shedding and the protective effect of rNV-specific fecal IgA (flgA) were investigated in volunteers who were repeatedly challenged with NV. After the first challenge, ill volunteers were significantly more likely than well volunteers to have NV antigen in their stool (P < .05). After challenge, antigen shedding was detected on days 1-13; ill volunteers shed the antigen longer (P = .02). A higher prechallenge rNV-specific flgA geometric mean titer was found in ill compared with well volunteers (P < .05) and in infected versus noninfected volunteers (P < .05). NV shedding was common after infection and was present up to 2 weeks after challenge. Preexisting rNV-specific flgA, like serum IgG, is not protective and may be a marker for symptomatic disease. PMID- 7876603 TI - Adenovirus-mediated blockade of tumor necrosis factor in mice protects against endotoxic shock yet impairs pulmonary host defense. AB - A replication-deficient recombinant adenovirus encoding a chimeric protein capable of binding tumor necrosis factor (TNF) and lymphotoxin was given to mice. Administration of this virus (10(9) pfu intravenously) yielded high levels of the recombinant protein in plasma and afforded significant protection to a lethal challenge with lipopolysaccharide with or without D-galactosamine. However, this protein inhibitor was readily detectable in the lung and was associated with decreased neutrophil recruitment and bacterial killing after intratracheal LPS or Pseudomonas aeruginosa, respectively. These data reflect the dual role of many proinflammatory cytokines. This model of TNF inhibition is similar to the homozygous 55-kDa TNF receptor deletion; thus, adenovirus-mediated gene transfer of cytokine inhibitors in vivo is a useful tool to abrogate the function of single or multiple cytokines for investigational or therapeutic purposes. PMID- 7876604 TI - Analysis of the UL97 phosphotransferase coding sequence in clinical cytomegalovirus isolates and identification of mutations conferring ganciclovir resistance. AB - The UL97 phosphotransferase coding sequences of clinical cytomegalovirus (CMV) isolates, 10 resistant and 11 sensitive to ganciclovir, were compared to define mutations associated with drug resistance. In each ganciclovir-resistant isolate, a mutation was found that resulted in an amino acid substitution at codon 460 (4 isolates), codon 594 (2 isolates), or codon 595 (4 isolates). No sensitive isolate carried any of these mutations. Marker transfer studies showed that each mutation was capable of conferring ganciclovir resistance to the laboratory CMV strain AD169. Rapid diagnostic tests based on DNA amplification and restriction enzyme analysis were developed for these mutations. Specific mutant DNAs were detected when they constituted at least 10% of the population in the specimen. Several mutations in UL97 appear to be common markers for ganciclovir resistance, and their detection may be a rapid alternative to conventional cell culture susceptibility testing. PMID- 7876605 TI - Nasal cytokine production in viral acute upper respiratory infection of childhood. AB - Children in a day care center underwent serial nasal lavages in order to assess nasal cytokine expression during acute upper respiratory infections (URI). Interleukin (IL)-1 beta, IL-8, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were markedly elevated in nasal lavage fluid during acute URI compared to baseline, and all except TNF-alpha decreased significantly by 2-4 weeks later. Cytokine patterns in respiratory syncytial virus-positive and -negative illnesses did not differ significantly. A subgroup of children also underwent superficial mucosal biopsy under the inferior nasal turbinate. During acute URI, biopsy cells (90%-95% epithelial) showed increased transcripts for IL-1 beta, IL-8, and IL-6 in 7 of 9 subjects, suggesting that epithelial cells may be one source of cytokines during acute URI. The results show that inflammatory cytokines are elevated in nasal secretions during acute URI in preschool children. Thus, cytokines are likely to participate in regulation of respiratory virus-induced inflammation. PMID- 7876606 TI - Group A streptococcus-liposome ELISA antibody titers to group A polysaccharide and opsonophagocytic capabilities of the antibodies. AB - Antibodies reactive with group A streptococci (GAS) carbohydrate were studied by ELISA and in an indirect bactericidal assay. The ELISA used GAS carbohydrate covalently bound to phosphatidylethanolamine incorporated into liposomes so that both precipitating and nonprecipitating antibodies were measured. Sera from children from different geographic areas exhibited marked differences in levels of anti-GAS carbohydrate antibody, which increased with age. The antibodies were predominantly of IgG. In bactericidal assays, most of these sera promoted phagocytosis of several type-specific M-positive strains. Opsonization was also related to serum levels of anti-GAS carbohydrate antibodies. These opsonizing antibodies were depleted from the serum by absorption of the sera on an N-acetyl D-glucosamine affinity column. Antibody eluted from this column could partially restore opsonization of GAS. Anti-GAS carbohydrate antibodies play a major role in these opsonophagocytosis assays. PMID- 7876607 TI - M proteins of group G streptococci: mechanisms of resistance to phagocytosis. AB - Group G streptococci that express M protein and resist phagocytosis in human blood (virulent strains) were compared with strains of groups G and A that are readily phagocytosed (avirulent). Virulent group G streptococci were less effective (P < .05) as activators of the alternative complement pathway (ACP) than were avirulent streptococci. In immunofluorescence studies, C3 bound more avidly to avirulent than to virulent group G streptococci. Resistance of virulent group G strains to ACP opsonization and to phagocytosis was markedly diminished by removal with pepsin of the type-specific portion of the M molecule. Preincubation with fibrinogen did not diminish ACP activation or C3 binding by virulent group G and A streptococci but did exert an antiphagocytic effect. Given the similarity of M proteins of groups G and A in structure and function, other microbial constituents are likely responsible for differences in the spectra of illnesses attributable to the two serogroups. PMID- 7876608 TI - Eradication of endemic methicillin-resistant Staphylococcus aureus infections from a neonatal intensive care unit. AB - To control infections with endemic methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal intensive care unit (NICU), triple dye was applied to the umbilical cords of infants in the intermediate-care but not the intensive-care area. The rate of MRSA infection, adjusted for time and intensity of care, decreased in the intermediate-care area (rate ratio, 0.35; 95% confidence interval [CI], 0.14-0.87; P < .01) but not in the intensive-care area (rate ratio, 0.92; 95% CI, 0.41-2.24; P = .48). After 22 months, the rate increased in both areas (Mantel-Haenszel rate ratio, 1.7; 95% CI, 1.0-2.8; P < .05) after overcrowding and understaffing increased. After temporary reduction of overcrowding and understaffing, extension of triple dye use to the intensive-care area and dedication of an infection control nurse to the NICU, MRSA colonization and infection rates decreased to near zero in both areas (infection rate ratios, 0.09 and 0.11, respectively; P < .005). The endemic MRSA strain, identified by pulsed-field gel electrophoresis, was eradicated. PMID- 7876609 TI - Intestinal carriage of P fimbriated Escherichia coli and the susceptibility to urinary tract infection in young children. AB - This prospective study analyzed the intestinal carriage of P fimbriated Escherichia coli as a host susceptibility factor in urinary tract infection (UTI). P fimbriation was defined by the pap and G adhesin (papG1A2, prsGJ96) genotypes. Children with UTI carried pap+ E. coli in the fecal flora more often than healthy controls both at diagnosis (86% vs. 29%) and during infection-free intervals (approximately 40%; P < .01). P1 blood group-positive children carried pap+ E. coli in the fecal flora more often (88%) than those with P2 blood group (40%; P < .05). A pap+ E. coli strain caused UTI in 53 of 55 patients who carried both pap+ and pap- strains in their fecal flora. These results suggest that persons who develop UTI have an increased tendency to carry pap+ E. coli in the large intestine and that these pap+ E. coli cause UTI more often than pap E. coli strains in the fecal flora of the same host. PMID- 7876610 TI - A trial of a group A plus group C meningococcal polysaccharide-protein conjugate vaccine in African infants. AB - The safety and immunogenicity of a group A plus group C meningococcal polysaccharide-CRM197 conjugate vaccine was evaluated in 304 8- to 10-week-old Gambian infants. Infants were immunized with one, two, or three doses of conjugate vaccine or with two doses of a meningococcal A plus C polysaccharide vaccine. The conjugate vaccine produced few systemic side effects, and local reactions were similar to those produced by the polysaccharide vaccine. Postvaccination group A meningococcal polysaccharide antibody levels, measured by ELISA, increased progressively after one, two, or three doses of conjugate vaccine. However, one dose of conjugate vaccine given at the age of 6 months induced a higher group C meningococcal antibody response than did two doses of conjugate vaccine given at 2 and 6 months. Two doses of conjugate vaccine induced higher levels of antibody than did two doses of polysaccharide vaccine. Thus, this new meningococcal conjugate vaccine proved to be safe and immunogenic. PMID- 7876611 TI - A recombinant cysteine-rich section of the Entamoeba histolytica galactose inhibitable lectin is efficacious as a subunit vaccine in the gerbil model of amebic liver abscess. AB - The 170-kDa subunit of the galactose-inhibitable adherence lectin of Entamoeba histolytica mediates attachment to colonic mucins and host cells. The DNA fragment encoding the 170-kDa subunit was produced by polymerase chain reaction (PCR) and divided into four sections by restriction endonucleases. The third section (designated LC3, base pairs 2273-3397) encodes a cysteine-rich fusion protein that was recognized by adherence-inhibitory anti-lectin monoclonal antibodies and serum antibodies from 95% of subjects with amebic liver abscess. Immunization of gerbils with purified recombinant LC3-encoded protein (10 micrograms) with Titermax adjuvant elicited a high-titer serum anti-LC3 IgG antibody response and protective immunity against intrahepatic challenge with 0.5 x 10(6) virulent axenic trophozoites (strain HM1:IMSS; 71% vaccine efficacy, P < .01). In summary, a recombinant cysteine-rich portion of the 170-kDa lectin subunit was highly antigenic, immunogenic, and effective as a subunit vaccine in an experimental animal model of amebic liver abscess. PMID- 7876612 TI - Immunity to onchocerciasis: putative immune persons produce a Th1-like response to Onchocerca volvulus. AB - Immunity to Onchocerca volvulus (Ov) infection is suggested by the presence of putatively immune (PI) subjects in a region of Ecuador in which Ov is endemic. PI subjects were identified by traditional diagnostic methods combined with a polymerase chain reaction-based assay for Ov DNA in skin snips. Responses of peripheral blood mononuclear cells (PBMC) from the PI group (n = 16) were compared with those of persons with active infection (microfiladermic [MF] subjects; n = 51). PBMC of PI subjects proliferated significantly more to Ov antigen (OvAg; P < .009) than did PBMC of MF persons but less to streptolysin-O (P < .001). Cytokine analysis of PBMC culture supernatants revealed that PI subjects (n = 11) produced significantly more interferon-gamma to OvAg than did those in the MF group (n = 18; P = .018), less interleukin (IL)-5 to nonparasite antigen (P = .003) and mitogen (P = .012), and less IL-10 spontaneously (P = .016). Thus, immunity to Ov may in part be mediated by an antigen-specific Th1 type response. PMID- 7876613 TI - Immune responsiveness and the pathogenesis of human onchocerciasis. AB - Prominent antibody but minimal cellular proliferative responses to parasite antigen typify the systemic immune response of patients with onchocerciasis. While components of this response are proinflammatory (and antiparasitic), the primary force driving the immune system is the need to contain or limit inflammation around microfilariae that die in the skin or elsewhere at rates up to hundreds of thousands per day. These dying parasites initiate local inflammatory reactions, with the result being "bystander" tissue damage, which cumulatively determines host pathology. Local and systemic immune mechanisms to contain inflammation (e.g., blocking antibodies, down-regulating cytokines) are prominent in infected patients, and their delineation is crucial to understanding the pathogenesis of onchocercal disease in the skin, eye, and elsewhere. The degree of pathology appears directly related to both microfilarial numbers and the intensity of proinflammatory responses to them and inversely related to the effectiveness of specific mechanisms to suppress this inflammation. PMID- 7876614 TI - Hepatitis C virus RNA in the bone marrow of patients with mixed cryoglobulinemia and in subjects with noncryoglobulinemic chronic hepatitis type C. AB - Hepatitis C virus (HCV) infection is associated with most mixed cryoglobulinemia (MC) syndromes. In this study, HCV RNA was detected in the peripheral blood mononuclear cells of 11 (73.3%) of 15 patients with MC and in 5 (71.4%) of 7 noncryoglobulinemic patients with chronic hepatitis type C. All patients with cryoglobulinemia and 3 (42.8%) of the 7 without cryoglobulinemia (P < .05) had HCV RNA in bone marrow cells. Subjects in both groups with HCV-positive bone marrow also had HCV RNA in serum. The majority of patients with MC syndromes were infected with HCV subtypes 1b and 2a. Two patients with MC had different genotypes in serum and cells. Further studies are needed to determine which bone marrow cell population is preferentially infected by HCV and to determine if this phenomenon is involved in inducing the production of cryoglobulins. PMID- 7876615 TI - Immunogenicity of an inactivated hepatitis A vaccine in Alaska Native children and Native and non-Native adults. AB - The response to an inactivated hepatitis A vaccine was assessed in 307 persons: 163 Alaska Native children, ages 3-6 years, and 144 Native (84) and non-Native (60) adults. All adults received the same vaccine schedule (0, 1, and 12 months), whereas children were randomized to receive three different schedules (0, 1, and 6; 0, 1, and 2; or 0, 1, and 12 months). After one dose, 141 (96%) of 147 children and 129 (90%) of 143 adults responded with levels of antibody to hepatitis A virus > 20 mIU/mL. After three doses, all participants responded. The geometric mean titer (GMT) 1 month after the third dose was significantly higher in children who received the third dose 12 months after the first dose rather than 2 months after the first dose. While there were differences in the GMT of some blood samples by age, sex, and ethnicity, all participants responded to the vaccine. PMID- 7876616 TI - An outbreak of measles at an international sporting event with airborne transmission in a domed stadium. AB - An outbreak of measles occurred in conjunction with the International Special Olympics Games in the Minneapolis-St. Paul metropolitan area during July 1991. Sixteen outbreak-associated cases of measles were reported among US residents from seven states, with 9 additional cases resulting from subsequent transmission. The primary case was a track and field athlete from Argentina. Transmission occurred in three settings: the opening ceremonies in a domed stadium, track and field events, and first aid stations. Eight secondary cases had their only potential exposure at the opening ceremonies; 2 of these cases were unrelated spectators sitting in the same section of the upper deck > 30.5 m above the athlete's entrance. These findings demonstrate that the risk of indigenous measles transmission associated with international events in the United States must be considered, even in areas without recent measles activity. Moreover, the dynamic airborne transmission of measles illustrates the potential for transmission in the absence of a recognized exposure. PMID- 7876617 TI - Elevated levels of activities of beta-hexosaminidase and alpha-mannosidase in human immunodeficiency virus-infected patients. AB - To determine their value as markers of the clinical stage of human immunodeficiency virus (HIV) disease, plasma activities of lysosomal glycosidases were determined in the plasma of 97 HIV-infected patients: molecular forms of cathepsin D were characterized by Western blot to examine the mode of enzyme release. In patients with Centers for Disease Control and Prevention stage II and III of HIV disease, plasma activity of beta-hexosaminidase was significantly increased. In patients with stage III infection, alpha-mannosidase activity was also significantly increased and cathepsin D was elevated and present only in its premature form. Thus, determination of plasma activities of beta-hexosaminidase and alpha-mannosidase in HIV-positive persons may be useful for distinguishing the clinical stage of disease. The elevation of precursors of cathepsin D in patients with stage III HIV disease indicates that secretion of lysosomal enzymes rather than leakage of enzymes from damaged cells is markedly elevated. PMID- 7876618 TI - Rapid progression to disease in African sex workers with human immunodeficiency virus type 1 infection. AB - From a cohort of female sex workers in Nairobi, Kenya, 163 women were observed to seroconvert to human immunodeficiency virus type 1 (HIV-1) and followed to study progression to HIV-1-related disease. The effect of several covariables on disease progression was studied using a Weibull proportional hazards model. The Weibull survival model was fitted to the observed incubation times. Estimates of the median duration to CDC stage IV-A and IV-C disease were 3.5 and 4.4 years, respectively. Condom use before seroconversion was associated with a reduced risk of CDC stage IV-A disease (relative risk = .64, P < .05). The incubation time of HIV-1-related disease is extremely short in this population. PMID- 7876619 TI - Factors associated with early clinical recognition of children with perinatal human immunodeficiency virus infection. Northern California Pediatric HIV Consortium. AB - Surveillance of children born to women with human immunodeficiency virus (HIV) infection at five pediatric regional centers assessed times and patterns of clinical recognition in these children. Regional HIV seroprevalences among childbearing women were used to assess the proportion of identified children born to HIV-infected women. In total, 415 children with perinatal HIV exposure were identified. Early age at first HIV evaluation was significantly associated with maternal intravenous drug use (3.2 vs. 7.2 months for other or unknown maternal risk, P = .01), birth county with population > 500,000 (3.5 vs. 8.2 months for population < or = 500,000, P = .003), and hospital with routine HIV screening of pregnant women (0.1 vs. 8.8 months for no screening, P = .006). Race did not correlate with age at first evaluation. Using maternal HIV seroprevalence rates for 1988-1991, 34%-50% of the expected number of infants born to HIV-infected women were in clinical care. Perception of increased maternal risk for HIV infection was associated with early clinical recognition of infants of HIV infected women. PMID- 7876620 TI - The risk of human T cell leukemia virus and viral hepatitis infection among US Marines stationed in Okinawa, Japan. AB - The prevalence and incidence of human T cell leukemia virus type I/II (HTLV-I/II) and hepatitis A, B, and C virus infection were determined among US Marines stationed in Okinawa, Japan. Of 2875 personnel, 2 (0.07%) had antibody to HTLV I/II. After 1-3 years, no HTLV seroconversions were observed, although 23% reported sexual contact with Okinawans. Of 1010 hepatitis-tested marines, 121 (12%) had antibody to hepatitis A virus (anti-HAV), 26 (2.6%) had antibody to hepatitis B core antigen (anti-HBc), and 2 (0.2%) had antibody to hepatitis C virus (anti-HCV). On follow-up, 1 subject seroconverted to anti-HAV, 8 to anti HBc, and none to anti-HCV. Most marines with recent hepatitis B infection were young, single, and enlisted and had been on short deployments to other countries in Southeast Asia. Marines stationed in Okinawa are not at high risk for HTLV infection but are at increased risk for hepatitis B infection and should be considered for vaccination. PMID- 7876621 TI - Sequence variation in the extreme 5' end of the human papillomavirus type 6a long control region. AB - A sequence analysis of human papillomavirus (HPV) type 6a isolates from 15 exophytic condylomata acuminata lesions was done to determine the prototype sequence for this region of HPV 6a, which sequences are conserved and which vary, and whether the variability might be useful in epidemiologic studies. The long control region (LCR) was amplified by the polymerase chain reaction and approximately 242 bp were directly sequenced. The data indicate that all isolates contain a 94-bp insertion relative to prototype HPV 6b and confirm that this insertion should be considered a part of the HPV 6 LCR. Seven of the 15 isolates were in 1 group, and the rest were distributed among 4 groups. There was no strong correlation between DNA group and location of lesion, sex of patient, or pregnancy status. In addition, although there was variation among isolates, a region implicated by deletional analysis to have transcriptional silencing activity was conserved. PMID- 7876622 TI - Racial differences in the occurrence of herpes zoster. AB - The purpose of this study was to determine if there are racial differences in the occurrence of herpes zoster (shingles). The study population was the Duke Established Populations for Epidemiologic Studies of the Elderly, a probability sample of community-dwelling persons > 64 years old in North Carolina. Interviewers administered a comprehensive health survey to the participants that included questions about lifetime occurrence of shingles. Of the 3206 subjects, 316 (9.9%) had had zoster: 81 (4.5%) of 1754 blacks and 235 (16.1%) of 1452 whites had had shingles (P < .0001). After controlling for age, cancer, and demographic factors, blacks remained one-fourth as likely as whites (adjusted odds ratio 0.25, 95% confidence interval 0.18-0.35; P = .0001) to have experienced zoster. In summary, blacks had a significantly lower risk of developing herpes zoster than whites, a new finding in herpes zoster epidemiology. PMID- 7876623 TI - Human cytomegalovirus immediate early and late transcripts in peripheral blood leukocytes: diagnostic value in renal transplant recipients. AB - Peripheral blood leukocytes of renal transplant recipients were investigated to compare the following markers of human cytomegalovirus (HCMV) infection: pp65 antigen by indirect immunofluorescence, viral DNA by nested polymerase chain reaction (PCR), and immediate early (IE) and late (pp150) mRNA by nested PCR following reverse transcription. Sixty-five patients were monitored weekly for 20 weeks after transplantation. In 76 samples from 20 patients positive for HCMV DNA by PCR, HCMV mRNA was detected. Detectable amounts of IE and pp150 mRNA were positively correlated with high numbers of pp65 antigen-positive cells and confirmed the significance of pp65 antigen as a marker for active viral replication. However, with respect to the early diagnosis of HCMV-related disease and monitoring of antiviral therapy, the test for viral mRNA was not superior to the pp65 antigen test. PMID- 7876624 TI - Accurate serodiagnosis of B19 parvovirus infections by measurement of IgG avidity. AB - In an attempt to improve diagnosis of illnesses caused by parvovirus B19 and to discriminate primary from secondary infections, a protein-denaturing assay for avidity of parvovirus-specific IgG antibodies was developed. The assay used three types of purified recombinant antigens: a fusion protein containing the unique portion of the structural protein VP1, entire capsids made up of the major structural protein VP2 alone, or VP2 plus VP1. The avidity assays were evaluated by testing sequential acute-phase serum samples from 61 well-characterized patients (34 were followed > or = 6 months), sera from 38 controls with evidence of past infection, and sera from 388 seropositive patients studied for evidence of B19 infection during an epidemic. Parvovirus capsids consisting of VP2 alone yielded unusual IgG avidity and IgG antibody responses. Three different IgG avidity assays based on VP1 protein antigens were highly sensitive and specific and were considered suitable for identification of recent primary infections by human parvovirus B19. PMID- 7876625 TI - Phase-variable expression of the 145-kDa surface protein of Brazilian purpuric fever case-clone strains of Haemophilus influenzae biogroup aegyptius. AB - Clonally related strains of Haemophilus influenzae biogroup aegyptius have recently been associated with Brazilian purpuric fever (BPF). Antibodies to a 145 kDa minor outer membrane protein (P145) are bactericidal and protect against experimental bacteremia. To determine if P145 is conserved among case-clone strains, case-clone strains were screened for P145 expression. Assays of a large number of colonies of each strain using colony immunoblot revealed colonies reactive with anti-P145 sera in all 17 case-clone strains. P145 was expressed at a low frequency (0.08%-2.2% of colonies) in 14 strains and at a high frequency (> 98%) in 3 strains. Expression of P145 by reactive colonies was confirmed by SDS PAGE. Also, anti-P145-nonreactive variant colonies of P145-expressing strains were detected in 0.4%-1.5% of colonies. These findings indicate P145 is conserved among BPF case-clone strains and is subject to phase-variable expression. PMID- 7876626 TI - Effect of secretor status on vaginal and rectal colonization with fimbriated Escherichia coli in women with and without recurrent urinary tract infection. AB - The prevalence and duration of rectal and vaginal colonization with P- and F fimbriated Escherichia coli and the relationship of colonization with these strains to blood group secretor status was investigated. Rectal and vaginal E. coli isolates were prospectively collected twice monthly for 6 months from 20 young women with and 20 without a history of recurrent urinary tract infection (UTI). Rectal and vaginal colonization with P- and/or F-fimbriated E. coli was highly prevalent. Nonsecretors who developed UTI during the study period were significantly more likely to be colonized rectally with F-fimbriated E. coli than were the infected secretors (56% vs. 27%; P = .042) or uninfected nonsecretors (56% vs. 31%; P = .046). Persistent vaginal and rectal E. coli colonization with fimbriated organisms occurred commonly in the study patients but was not often temporally associated with the development of UTI. Results suggest that nonsecretors are more susceptible than secretors to colonization with F adhesin bearing E. coli isolates. PMID- 7876627 TI - Inhibition of Shiga-like toxins by brefeldin A. AB - The effects of Shiga-like toxins on the morphology and protein synthetic capability of HeLa cells in tissue culture could be prevented by brefeldin A, an inhibitor of certain intracellular Golgi functions. Brefeldin A was without effect on the binding of Shiga-like toxin to cells. These results provide evidence that the Shiga-like toxins are first processed by the Golgi before moving to their 60S ribosome target site. PMID- 7876628 TI - Recombinant outer surface protein C ELISA for the diagnosis of early Lyme disease. AB - To compare the sensitivity of a new ELISA for IgM antibodies to Borrelia burgdorferi that uses a recombinant outer surface protein C (rOspC) with those of a whole cell (WC) ELISA and an immunoblot assay for the diagnosis of early Lyme disease, serum specimens from 82 consecutive patients with physician-documented erythema migrans were analyzed. To compare the specificities of the three assays, serum specimens from 50 patients without a history of Lyme disease and from an area in which B. burgdorferi is not endemic were analyzed. The sensitivities of the WC ELISA, immunoblot assay, and IgM rOspC ELISA were 28%, 29%, and 46%, respectively, while the specificities were 100%, 100%, and 98%, respectively. The IgM rOspC ELISA is a convenient, readily automated, easily standardized serologic test that is significantly more sensitive for the diagnosis of early Lyme disease than either WC ELISA or immunoblot assay. PMID- 7876629 TI - Eradication of nasopharyngeal carriage of Neisseria meningitidis in children and adults in rural Africa: a comparison of ciprofloxacin and rifampicin. AB - A randomized comparative study of rifampicin and ciprofloxacin for eradicating nasopharyngeal carriage of meningococci was undertaken in Malawi. Of 1878 contacts of persons with meningococcal meningitis, 1875 were evaluatable for safety and efficacy of the drugs. Rifampicin was given to 836 contacts, ciprofloxacin to 711, and ceftriaxone to 328 (children < 2 years old or pregnant or lactating women). One and 2 weeks after therapy, side effects in those given rifampicin and ciprofloxacin were not significantly different. In the ciprofloxacin group, with 470 subjects < 18 years old, only one event (mild abdominal pain) occurred that was related to the drug. Nasopharyngeal carriage was detected in 88 (10.5%) of those given rifampicin, 79 (11.1%) given ciprofloxacin, and 41 (12.5%) given ceftriaxone. Eradication rates after 1 and 2 weeks of treatment, respectively, were 96.5% and 97.7% for rifampicin, 88.6% and 91.1% for ciprofloxacin, and 95.1% and 97.6% for ceftriaxone. Ciprofloxacin provides a safe and effective alternative to rifampicin for eradication of meningococcal carriage in children 2-18 years old. PMID- 7876630 TI - Congenital syphilis surveillance in upstate New York, 1989-1992: implications for prevention and clinical management. AB - Descriptive characteristics and clinical information from 322 cases of congenital syphilis were reviewed. The births (318 mothers) included 31 (10%) stillborn and 59 (18%) with clinical evidence of congenital syphilis. Only 60 (19%) had a complete laboratory workup, including radiographs of long bones and spinal fluid analysis. For a subset of 244 women with available information, 218 (89%) had > or = 1 risk factors for syphilis; however, residence in an area with high morbidity from syphilis was the only identified risk factor for 83 (34%). Eighty women (25%) were treated for syphilis during pregnancy; only 24 were treated appropriately for their stage of syphilis > 30 days before delivery. Five of these pregnancies resulted in infants with clinical signs of syphilis. These findings emphasize the need for expanded prenatal screening of high-risk women, the necessity of screening at delivery, and the need for complete evaluation of infants at risk for congenital syphilis. Further, the data suggest that in some cases therapy in the last trimester of pregnancy may be insufficient to adequately treat the fetus. PMID- 7876631 TI - Systemic dissemination of Chlamydia pneumoniae following intranasal inoculation in mice. AB - Although Chlamydia pneumoniae is a respiratory pathogen, there is increasing evidence of involvement of the organisms in anatomic sites other than the respiratory tract. A mouse model was used to study dissemination of organisms following intranasal, intravenous, and subcutaneous inoculation with C. pneumoniae. After inoculation by any of the three routes, the organism was isolated consistently from lungs and spleen. It was also detected in peritoneal macrophages after intranasal and intravenous inoculation. The ease with which the organism was disseminated in the mouse model raises the question of whether similar spread from the respiratory tract occurs in human C. pneumoniae infection. PMID- 7876632 TI - Presence of bactericidal/permeability-increasing protein in disease: detection by ELISA. AB - A sandwich ELISA was developed specific for human bactericidal/permeability increasing protein (BPI), using Mg++ ions to abrogate disturbance by lipopolysaccharide of BPI measurement and to prevent aspecific adherence of BPI to solid phase. In fresh EDTA or heparinized plasma of healthy volunteers BPI was not detectable, whereas in serum BPI was present, indicating that coagulation activates polymorphonuclear leukocytes to release BPI. Furthermore, BPI was present in plasma of critically ill intensive care unit (ICU) patients, in bronchoalveolar lavage fluid of patients suspected of having pneumonia, in wound fluid, and in pleural fluid. In sub-groups of samples with culture-proven bacteria, mean BPI levels were increased compared with subgroups without bacteria, although the differences were only significant in EDTA plasma of ICU patients. These findings indicate the presence of BPI during pathologic conditions. The physiologic role of the released BPI has to be further elucidated. PMID- 7876633 TI - Impaired secretion and mRNA expression of monokines by alveolar macrophages from nonsmoking patients with alcoholic liver cirrhosis. AB - Alveolar macrophages (AM) exposed to microorganisms secrete cytokines that are important to lung defense. Since alcoholic liver cirrhosis (ALC) patients are susceptible to lung infections, the ability of AM in such patients to produce the cytokines tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 was evaluated by mRNA expression and protein secretion. Adherent AM from ALC and alcoholic patients and controls were cultured with and without lipopolysaccharide (LPS): Mean cytokine levels in ALC and alcoholic subjects were not significantly different than in controls. However, LPS-stimulated AM from 13 of 29 ALC patients exhibited a reduced ability, compared with that from controls, to secrete the cytokines (P < .05 for all 3). Specific mRNA expression was also impaired in the 13 patients, and their liver diseases were more severe than those of other patients. Impaired cytokine production by AM in ALC patients with severe cirrhosis may account for their increased susceptibility to lung infections. PMID- 7876634 TI - Reduced serum levels of clarithromycin in patients treated with multidrug regimens including rifampin or rifabutin for Mycobacterium avium-M. intracellulare infection. AB - The newer macrolides and rifamycins (rifabutin) are major advances for treatment or prophylaxis of disease due to Mycobacterium avium complex. Although rifampin and rifabutin are known to induce the hepatic cytochrome P-450 system, their impact on the metabolism of clarithromycin is unknown. Clarithromycin and its major metabolite, 14-OH clarithromycin, were measured in the sera of patients receiving 500 mg twice a day before and after the addition of antituberculous drugs, including 600 mg/day of rifampin or rifabutin. Mean serum levels of clarithromycin given as a single agent were 5.4 +/- 2.1 micrograms/mL. These decreased to 0.7 +/- 0.6 micrograms/mL in patients receiving rifampin and 2.0 +/- 1.5 micrograms/mL in those receiving rifabutin. Mean serum levels of 14-OH clarithromycin were similar in the 3 groups (1.8-1.9 micrograms/mL). Rifampin and (to a lesser degree) rifabutin appear to induce the metabolism of clarithromycin. PMID- 7876635 TI - Diagnosis of symptomatic visceral leishmaniasis by use of the polymerase chain reaction on patient blood. AB - To diagnose symptomatic visceral leishmaniasis (kala-azar) using peripheral blood rather than tissue aspirates, a polymerase chain reaction (PCR) technique was developed for which the detection limit is 1 Leishmania-infected macrophage in 8 mL of blood. For Indian, Kenyan, or Brazilian patients with parasitologically confirmed kala-azar, 57 of 63 cases before treatment had blood that was PCR positive (90% sensitivity). None of 40 clinically healthy persons had PCR positive blood (100% specificity). Twelve (92%) of 13 clinically cured Indian patients had negative PCR reactions 1-6 months after treatment. This PCR procedure can provide a parasitologic diagnosis for the vast majority of kala azar cases before therapy, may identify patients who have been successfully treated by chemotherapy, and should substantially reduce the need for invasive tests. PMID- 7876636 TI - Clinical, parasitologic, and immunologic observations of patients with hydrocele and elephantiasis in an area with endemic lymphatic filariasis. AB - Hydrocele and elephantiasis, major clinical manifestations of bancroftian filariasis, are thought to share a common pathogenesis. The characteristics of 121 patients with hydrocele or elephantiasis in Leogane, Haiti, were compared: 39% of 57 men with hydrocele and 3% of 64 persons with lymphedema of the leg were microfilaria-positive (P < .001). Circulating filarial antigen, presumably from the adult worm, was detected in 15 (43%) microfilaria-negative men with hydrocele and 9 (15%) microfilaria-negative persons with leg edema (P = .004). Microfilaria positive men had lower levels of filaria-specific IgG1 and hydroceles of significantly smaller volume and shorter duration than did microfilaria-negative men; hydrocele volume was inversely associated with microfilarial density (P = .001). In contrast, filarial antigen but not microfilariae was associated with filaria-specific IgG4 and decreased lymphocyte proliferation. Antigen status was not associated with severity of leg edema. In this filariasis-endemic area, men with hydrocele are more immunologically and parasitologically heterogeneous than are persons with elephantiasis. PMID- 7876637 TI - The spread of Vibrio cholerae O139 in India. PMID- 7876638 TI - Pneumonia and bacteremia by pneumococcal serotype 16 in a human immunodeficiency virus-infected child with normal serum antibody response to 23-valent pneumovax vaccine. PMID- 7876639 TI - Seroprevalence study of hantavirus antibodies in Pima Indians with renal disease. PMID- 7876640 TI - An overview of the clinical development of hepatitis A vaccine. Proceedings of a meeting. Marco Island, Florida, 3-6 February 1994. PMID- 7876641 TI - Clinical manifestations of hepatitis A: recent experience in a community teaching hospital. AB - A study of the clinical profile of 59 patients who presented with hepatitis A virus infection showed that dark urine, fatigue, gastrointestinal complaints, and fever were the most common presenting symptoms. The most frequent physical findings were hepatomegaly and jaundice. The mean presenting laboratory tests included total bilirubin of 5 mg/dL, alkaline phosphatase of 269 units/L, and serum aspartate aminotransferase and alanine aminotransferase levels of 1442 mIU/mL and 1952 mIU/mL, respectively. Atypical manifestations included relapse, cholestasis, rash, and arthralgia. Two patients presented with hepatitis A and concomitant type I autoimmune chronic hepatitis, and both required immunosuppressive therapy. Five patients who presented with hepatitis A were pregnant, and during follow-up, none of their infants developed elevated serum transaminase values or had detectable IgM anti-HAV antibody. All 59 patients experienced complete clinical and biochemical recovery within 6 months after onset of illness. PMID- 7876642 TI - Seroepidemiology of hepatitis A in the United States. AB - The seroepidemiology of hepatitis A depends on the biologic features of the agent. Hepatitis A virus (HAV) is shed in the stool, and infectivity titers are significantly higher for stool than for other body materials. As a consequence, the predominant mode of spread is through fecal-oral routes. Common-source vectors include contaminated foods, water, and bivalve mollusks. Risk factors include contact with a person with hepatitis A, attendance or employment at a day care center, recent international travel, exposure to infected food or water during an outbreak, homosexual activity, and injecting drug use. No known risk factors are identified in many cases. Almost 40% of individuals in the United States are seropositive for prior HAV infection, and rates increase with age, perhaps reflecting an aging cohort of persons infected in earlier times when the infection was more common. Not unexpectedly, this decrease in current infection rates has increased the number of susceptible persons. PMID- 7876643 TI - History and epidemiology of hepatitis A virus. AB - Hepatitis A was clearly recognized as an entity separate from other types of hepatitis during World War II, but only later did studies provide convincing evidence of the prevalence and transmission of hepatitis A virus (HAV). Disease incidence varies over time and geography, with wide differences from country to country and even within cities. Noted recently is a shift in prevalence in cases from childhood to adulthood. Incidence figures are unreliable. Epidemiology of the disease is best defined by measurement of anti-HAV antibodies. HAV is a very stable virus, frequently found in urban sewage. Infections occur early in life when sanitation is poor and living conditions crowded, but improvements in sanitation and hygiene have delayed infection, resulting in increasing numbers of adults susceptible to HAV. Transmission of HAV by blood is rare. High-risk persons include injection drug users, institutionalized persons and their caretakers, and those who travel from low-prevalence to high-prevalence countries. PMID- 7876644 TI - Hepatitis A in travelers: the European experience. AB - Each year approximately 14 million Europeans travel to developing countries in Africa, Asia, and Latin American as well as to infrequently visited countries in eastern Europe. Without protection, travelers develop symptomatic hepatitis A at the rate of 3 cases per 1000 people per month of stay. Those who eat and drink under poor hygienic conditions have an even higher risk, 20/1000/month. Studies show that hepatitis A is the most frequent vaccine-preventable disease in travelers to developing countries. Immunity to hepatitis A virus is infrequent among northern European travelers, except for those born before 1945, with a history of jaundice, or who lived for > 1 year in a developing country. PMID- 7876645 TI - Hepatitis A and the American traveler. AB - Morbidity from hepatitis A in American travelers may be greater than currently recorded. Risks for acquiring hepatitis A are widespread in developing countries, and a single lapse from appropriate hygiene for food or water is sufficient to cause infection. In Peace Corps personnel, a strictly regulated policy of immune serum globulin (ISG) at 4-month intervals reduced the rate of hepatitis A to 0.1 0.3 cases (from 1.6-2.1 cases)/100 persons/year. Data from United States Foreign Service personnel, for whom there is no mandated ISG policy, show hepatitis A to be the most commonly reported immunization-preventable infection; rates are 0.06 0.16/100 person-years, depending on the area of the world. With the availability of a hepatitis A vaccine, frequent travelers or those who stay long-term in hepatitis-endemic areas can attain higher antibody concentrations and much longer protection than is currently available from ISG. PMID- 7876646 TI - Approaches to a vaccine against hepatitis A: development and manufacture of an inactivated vaccine. AB - The basis for the development of a vaccine against hepatitis A was laid in the 1970s, when virus was replicated in cell culture. Adaptation to growth in cell culture resulted in attenuation and sufficient quantities of virus particles, allowing the development of both live attenuated and inactivated vaccines. Testing of candidate vaccines in volunteers began in the early 1980s. Recently, a formaldehyde-inactivated whole-virion hepatitis A vaccine, the first licensed vaccine against hepatitis A, was introduced in many countries worldwide, and a live attenuated vaccine became available in the People's Republic of China. Other possible avenues for vaccine development include the use of either conventional or recombinant DNA techniques to obtain subunit vaccines, empty capsids, live viral or bacterial vectors, genetic immunization, synthetic peptides, and anti idiotypes. PMID- 7876647 TI - Efficacy of an inactivated hepatitis A vaccine in pre- and postexposure conditions in marmosets. AB - A two-part challenge study was done in marmoset monkeys to confirm the efficacy of an inactivated hepatitis A vaccine. In part 1 (preexposure), 7 marmosets received a single low dose of vaccine (360 ELISA units [EL.U.]) and were challenged orally with wild type hepatitis A virus (HAV) either 1 or 6 months later. In part 2 (postexposure), 8 marmosets were challenged orally with HAV and then half each were inoculated with a single dose of 360 or 1440 EL.U. of vaccine 2 days later. The suboptimal immune response elicited by the low vaccine dose in the preexposure group was sufficient to induce complete protection against oral challenge with heterologous HAV in all marmosets that had responded serologically. In the postexposure group, the 360-EL.U. dose of vaccine resulted in partial protection against hepatitis A disease, whereas the 1440-EL.U. dose of vaccine elicited complete protection against disease and virus excretion. PMID- 7876648 TI - Clinical experience with an inactivated hepatitis A vaccine. AB - Clinical trials of an inactivated hepatitis A vaccine have encompassed 104 studies completed by December 1993 in 27 countries. Studies involved 50,677 subjects and administration of > 120,000 vaccine doses. Results show that the vaccine is safe, clinically well-tolerated, and highly immunogenic in all age groups. A seroconversion rate of 100% is achieved 1 month after primary vaccination. Vaccine-induced antibody titers persist after a primary vaccination course for > or = 1 year with a single dose of 1440 ELISA units (EL.U.) in adults and after two doses of 360 EL.U. in children. A booster dose 6-12 months after the first vaccine dose induces very high antibody titers, which according to a mathematical model, are expected to protect against hepatitis A for > 20 years. The vaccine is equally immunogenic when administered simultaneously with other traveler vaccines, therefore enabling flexible and convenient vaccination against hepatitis A. PMID- 7876649 TI - Inactivated hepatitis A vaccine: a safety and immunogenicity study in health professionals. AB - The safety and immunogenicity of an inactivated hepatitis A vaccine (HM175) were evaluated in 151 seronegative health professionals (age range, 21-65 years; mean, 30). A 720-ELISA unit dose was administered to 78 vaccinees at 0, 1, and 6 months and to 73 vaccinees at 0, 1, and 12 months. Seroconversion rates were 90% in both groups 1 month after the first inoculation and 99% and 100%, respectively, 1 month after the second inoculation. Geometric mean antibody titers (GMTs) 1 month after the third inoculation were highest in the group vaccinated at 0, 1, and 12 months. GMTs were higher in women than in men. The vaccine was well tolerated; the most frequent side effect was transient soreness at the site of inoculation. No serious adverse reactions were observed. Thus, HM175 inactivated hepatitis A vaccine is safe and highly immunogenic. PMID- 7876650 TI - Administration of hepatitis A vaccine to a military population by needle and jet injector and with hepatitis B vaccine. AB - Military personnel are an important target population for hepatitis A immunization. Soldiers are often given vaccines by jet injector and may be required to receive multiple vaccines at one time. Formalin-inactivated hepatitis A vaccine containing 360 ELISA units of antigen was evaluated at Fort Campbell. Volunteers received vaccine at 0, 1, and 6 months as follows: group 1, hepatitis A vaccine by needle; group 2, hepatitis A vaccine by jet injector; group 3, hepatitis B vaccine by needle; and group 4, both hepatitis vaccines by needle in separate arms. Immune response and reactogenicity were evaluated. After two doses, recipients of vaccine administered by jet injector had a higher prevalence of antibody than those who received vaccine by needle (93% vs. 79%). By the 8th month, the vaccine was 100% immunogenic by either route or with hepatitis B vaccine. No interaction between hepatitis A and B vaccines was detected. PMID- 7876652 TI - Safety and immunogenicity of an inactivated hepatitis A vaccine in preschool children. AB - Young children in day care centers are an important source of hepatitis A virus (HAV) infection. The safety and immunogenicity of an inactivated HAV vaccine was evaluated in 57 children in day care centers. Nonimmune healthy children were given 0.5 mL of vaccine with subsequent doses: group A (28 children), second and third doses 1 and 2 months after the first; group B (29 children), second and third doses at 1 and 6 months. Antibody to HAV was measured before each dose and 8 months after the initial dose. All children developed antibody to HAV. Groups A and B had similar levels of antibody at 2 months; levels were lower in group B before the third dose and higher 8 months after the first dose. Local reactions after vaccination were reported in 17 children (29.8%). Minor systemic side effects that cleared spontaneously were observed in 27 children (47%). PMID- 7876651 TI - Immunization of US soldiers with a two-dose primary series of inactivated hepatitis A vaccine: early immune response, persistence of antibody, and response to a third dose at 1 year. AB - To study the feasibility of using inactivated hepatitis A vaccine for rapid immunization of US soldiers, 276 randomized seronegative volunteers received one of four regimens: two injections, on day 0 or one each on day 0 and 14, day 0 and 30, or day 0 and 180. A third dose was given on day 380. Among the 256 recipients of two doses, 99% responded with antibody (by ELISA) with few symptoms. A higher percentage of recipients of both doses on day 0 had antibody at day 14 (68% vs. 52% of all others, P < .03). The highest antibody concentrations (711 mIU/mL on day 240) were observed in subjects given a second dose on day 180. Recipients of the third injection developed a median 15-fold rise in antibody within 2 weeks. Virus-neutralizing antibody was detected in high titers after the third dose and neutralized strains of hepatitis A virus from several countries. Vaccines containing 1440 ELISA units of antigen may be useful for rapid immunization. PMID- 7876653 TI - Discussion: who should receive hepatitis A vaccine? A strategy for controlling hepatitis A in the United States. PMID- 7876654 TI - Host immune response to hepatitis A virus. AB - Hepatitis A virus (HAV) is transmitted by the fecal-oral route. The virus crosses through the gastrointestinal tract by an uncharacterized mechanism and travels to the liver, where it replicates in hepatocytes. It is released into the bloodstream and is simultaneously present in the bile and shed in the feces. Fecal shedding and viremia are maximal at the onset of liver function abnormalities and terminate about the time humoral immunity is detected, approximately 28 days after exposure. IgM, IgA, and IgG anti-HAV antibodies are usually present at onset of symptoms. Although the IgM response becomes undetectable usually within 6 months, IgG responses frequently persist for life, providing protection against reinfection. Pre- and postexposure immunization with pooled human serum immunoglobulin (ISG) is approximately 90% effective in preventing hepatitis A. Recipients of ISG have very low levels of detectable anti HAV antibodies, and vaccines that elicit anti-HAV levels comparable with those produced by ISG should confer similar protection. PMID- 7876655 TI - The cineless catheterization laboratory. PMID- 7876656 TI - Which media are most likely to solve the archival problem? AB - The clinical application of quantitative methods for coronary arteriography remains limited, due in large part to the absence of a suitable replacement for cinefilm as the procedure record. The extension to the clinical environment of the validated objective methods which have found such widespread acceptance in clinical research studies is difficult to implement if the time-consuming and variable process for digitization of selected cinefilm frames is required. In addition, the complete integration of the angiographic procedure record with other patient records and procedures stored in a digital data format requires that the angiographic data eventually be converted to a digital format as well. Replacement of cinefilm requires that the media chosen for the task provide at least the same capabilities and preferably improved functions as those provided by cinefilm as a display, transport, and archival media. The demanding set of requirements imposed on the replacement options include high capacity, high acquisition rate, high transfer rate, application in a distributed environment, portability between institutions, and low expense. A true digital solution should also provide immediate access to the results of the angiographic procedure, transfer of image data over digital networks, multiple-user viewing capability, and quantitative analysis on a routine basis for all patients. In fact, a single media may not provide all the capabilities listed above but, rather, different media may need to be used for specialized tasks, i.e. the solution for archival may not be the same that will be employed as the portable patient record. Separation of the archival function from the acquisition/display and portable transfer functions increases the likelihood that cinefilm can be replaced in the imminent future by reducing the demands on a single media. Among the archival options available today are: (1) magnetic disks; (2) analog laser optical disks; (3) digital laser optical disks; (4) digital file-based magnetic tape; (5) digital video magnetic tape. In evaluating each of these alternatives, an accounting is required of how each meets the archival requirements along with an approximate breakdown of cost and readiness for implementation as a clinical solution today. PMID- 7876657 TI - Correlation between clinical course and quantitative analysis of the ischemia related artery in patients with unstable angina pectoris, refractory to medical treatment. Results of two randomized trials. The European Cooperative Study Group. AB - Patients with unstable angina, refractory to intensive medical therapy, are at high risk for developing thrombotic complications, such as recurrent ischemia, myocardial infarction and coronary occlusion during coronary angioplasty. As both platelet aggregation and/or thrombus formation play an important role in this ongoing ischemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) or thrombolytic therapy (alteplase) might be able to modify the clinical course and underlying coronary lesion morphology. To evaluate whether alteplase or c7E3 could influence the incidence of complications, we randomized 36 and 60 patients, respectively to alteplase or placebo, or c7E3 or placebo. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite maximal tolerated medical therapy. Patients were randomized in both studies after initial angiography had demonstrated a culprit lesion amenable for angioplasty. After study drug infusion quantitative angiography was repeated and angioplasty performed. Recurrent ischemia during study drug infusion occurred in 5, 6, 9 and 16 patients from the alteplase, placebo, c7E3 and placebo group, respectively. Major events defined as death, myocardial infarction or urgent intervention occurred in 7, 3, 1 and 7 patients, respectively. Two patients died: one in the alteplase group and one in the placebo group from the c7E3 study. The first patient due to retroperitoneal hemorrhage, the second as a result of recurrent infarction. Qualitative angiography showed resolution of clots in the c7E3 group only, while the same group of patients showed in 20% an improvement in TIMI flow grade, without deterioration in any patient from this group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876658 TI - Visualization of myocardial infarction six hours after injection of 111 In antimyosin antibodies using an image subtraction technique. AB - 111 In-antimyosin antibodies are capable of visualizing acute myocardial infarction (MI). Because of slow blood clearance, images are usually recorded 24 or 48 h postinjection. This pilot study was aimed at validating a blood pool subtraction technique, which makes it possible to visualize MI 6 h postinjection. Twenty-five patients with proven MI (16 anterior, 9 inferior) were imaged 10 minutes, 6 and 24 h after an injection of 110 MBq 111 In-labelled antimyosin antibodies, with a mean delay of two weeks after infarction. Three planar views were obtained each time. Using software which performs geometric registration, grey level normalization and subtraction of images, the blood pool image (obtained 10 minutes postinjection) was subtracted from the 6 hour image. The resulting image was the blood pool corrected 6 h image. The 24 h images and the blood pool corrected 6 h images were interpreted blindly and the number of correct, incorrect and indeterminate MI localizations were tabulated. The number of correct localizations was 19/25 for the standard 24 h images and 22/25 for the blood pool corrected 6 h images. With this blood pool subtraction method it was possible to visualize MI 6 h postinjection. Theoretically, this method could be applied six hours after myocardial infarction. PMID- 7876659 TI - Contrast echocardiography of the left ventricle an independent predictor of pulmonary artery pressure? AB - To test the hypothesis that left heart opacification is dependent on pulmonary artery pressure, we analyzed consecutively 12 patients with normal and 8 patients with abnormal pulmonary artery pressure with a new lung capillary stable echo contrast agent. Patients underwent contrast echocardiographic examination within 6 hours before right and left heart catheterization with 200 mg/ml and 400 mg/ml SHU 508A intravenously. The mean pulmonary artery pressure was 15.4 mmHg in the patients with normal pulmonary artery pressures and 46.4 mmHg in the patients with pulmonary hypertension (p < 0.000). Echocardiograms were video intensitometrically analyzed for intensity maximum (MAX), half-time of video intensity decay (T1/2), area under the intensity curve (AUC) in the right and left ventricle and transit time from left to right heart (TT). Patients with normal pulmonary artery pressure showed sufficient left heart opacification, in the left ventricle MAX was 37 +/- 15 IU, AUC measured 653 +/- 463 IUxs and T1/2 was 4.4 +/- 2.6 s, while patients with elevated pulmonary artery pressure showed no significant left heart opacification. In the left ventricle MAX was 8 +/- 10 IU (p = 0.006), AUC measured 66 +/- 108 (p = 0.003) and T1/2 was 2.0 +/- 2.0 s (p = 0.041). TT was significantly increased in patients with elevated pulmonary artery pressure (11.8 +/- 4.6 s versus 6.5 +/- 2.8 s in patients with normal pulmonary artery pressure, p = 0.005). Thus, elevated pulmonary pressure has a significant impact on left heart opacification, which may be used for diagnostic purposes. PMID- 7876660 TI - Automated extraction, labelling and analysis of the coronary vasculature from arteriograms. AB - For clinical decision-making and documentation purposes we have developed techniques to extract, label and analyze the coronary vasculature from arteriograms in an automated, quantitative manner. Advanced image processing techniques were applied to extract and analyze the vasculatures from non subtracted arteriograms while artificial intelligence techniques were employed to assign anatomical labels. Lumen diameters of 11 phantom vessels were assessed with an accuracy of 0.27 +/- 0.19 mm (dtrue = 0.45 + 0.92dmeasured; r > 0.99) and 0.21 +/- 0.15 mm (dtrue = 0.42 + 0.91dmeasured; r > 0.99), from cine and digital images, respectively. We collected a total of 15 routinely acquired cine arteriograms showing 74 vessel segments with 18 stenoses (severity larger than 30% assessed quantitatively), and 53 digital arteriograms showing 236 vessel segments with 69 stenoses. From the cine arteriograms we extracted 64 (86%) of the vessel segments without manual correction and 196 (83%) from the digital arteriograms. Repeated analysis (3 times) of the arteriograms by the same operator resulted in a standard deviation of the mean segment diameters (precision) of 0.064 mm for the cine-images and 0.020 mm for the digital images, while the standard deviations in the measurement of the minimal luminal diameter of the observed stenoses were 0.020 mm and 0.019 mm, respectively. The LAD artery, the septal and diagonal branches were correctly identified automatically in 86% of the segments. From these evaluations we conclude that our automated approach provides reliable tools for the assessment of multi-vessel disease, both in an off- and on-line environment. PMID- 7876661 TI - Clinical and angiographic variables affecting the progression of coronary artery disease as determined by quantitative angiography. AB - To assess by serial quantitative angiography, the significance of clinical and angiographic variables that affect the progression of coronary artery disease (CAD). Progression of disease by sequential angiography is unpredictable and the role of clinical risk factors controversial. Various intervention trials have demonstrated less progression and even regression in hyperlipidemic patients. Correlates of progression have included a younger age, unstable angina, and greater involvement of the coronary arteries, with few studies looking at angiographic features of individual lesions. Serial angiograms on 74 patients were analyzed by computer assisted quantitative angiography using absolute measurements. A total of 99 diseased segments were analyzed for progression defined as an absolute reduction of 20% in luminal cross-sectional area. A preliminary correlation coefficient was calculated for each of the clinical and angiographic variables to detect any association with progression, and the odds ratio determined. The presence of any of the clinical risk factors-diabetes, hypertension, serum cholesterol, smoking, and a family history of coronary disease could not predict progression. The use of beta blockers was three times less likely to be associated with progression (odds ratio 0.33). While the presence of distal disease was associated with progression of a more proximal lesion (odds ratio 2.4), eccentricity, branch point location, lesion length, calcification, thrombus, or the presence of collaterals did not influence progression of disease in an individual segment. In conclusion, the presence of any of the clinical risk factors could not predict progression of disease in an individual coronary segment as determined by serial quantitative angiography, and the use of beta blockers and the absence of coexistent distal disease was associated with less progression of disease in an individual coronary segment. This may be related to changes in wall stress, reduced platelet interactions, and the integrity and permeability of the vascular endothelium to lipids. PMID- 7876662 TI - Right atrial spontaneous contrast: echocardiographic and clinical features. AB - We describe the clinical and echocardiographic findings in eight patients with right atrial spontaneous echo contrast who were identified from 648 consecutive patients undergoing transesophageal echocardiography. Common findings in these patients were right atrial enlargement (8 patients), tricuspid regurgitation (7 patients), atrial fibrillation or flutter (6 patients), elevated right ventricular pressure (5 patients), moderate or severe mitral valve disease (5 patients), and right to left interatrial shunts (3 patients). Right heart catheterization in three patients showed markedly elevated right atrial, right ventricular, and pulmonary artery pressures. Two patients had thromboembolic events-one patient had recurrent pulmonary emboli, and another patient with an atrial septal aneurysm had recurrent transient ischemic attacks. Right atrial echo contrast is an uncommon finding at echocardiography that is associated with severe right heart dysfunction. It may also be associated with paradoxical or pulmonary embolism. PMID- 7876663 TI - Magnetic resonance imaging of the heart in a case of hepatocellular carcinoma extending into the right atrium. AB - Hepatocellular carcinoma is the most common primary malignant liver tumor occurring in more than 1 million cases a year all over the world. Vascular invasion is known to occur in 30% of patients at initial presentation [1]. An extension of the tumor into the right atrium is well described in the literature [2], with surgical resection as the only procedure available. But the diagnosis is often difficult before death. We report a case in which magnetic resonance imaging of liver and heart shows the extension of this tumor into the right atrium. PMID- 7876664 TI - Hoogendoorn Prize 1993 for Hans Reiber. PMID- 7876665 TI - [Isolation of Bordetella pertussis from patients with pertussis-like symptoms and estimation of vaccine efficacy]. AB - In order to investigate the distribution of Bordetella pertussis in Nagoya City and estimate efficacy of the vaccine, we tried to isolate B. pertussis from patients with Pertussis-like symptoms who went to the department of pediatric general hospitals in Nagoya City from 1989 to 1992. B. pertussis were isolated from 43 patients among 164 patients with Pertussis-like symptoms. All of these isolates were classified into 1, 3, 6 serotype. It was impossible to isolate any B. pertussis in 1992 because of yearly variations. B. pertussis was only isolated from patients who were not vaccinated. Among the 28 siblings of the patients, 18 were vaccinated and 2 fell ill, but the latter had only mild symptoms. Three did not fall ill although they had an incomplete vaccination. According to these results we suggest that this component vaccine is effective. PMID- 7876666 TI - [Biological characters of enterohemorrhagic Escherichia coli isolates from diarrhea patients in Saitama (1990-1992)]. AB - A total of 16 strains of Enterohemorrhagic Escherichia coli (EHEC) isolated from diarrea patients in Saitama from 1990 to 1992 were tested for their serotype, verotoxin production, biochemical characteristics, antibiotics sensitivity and plasmid profiles. By serotype analysis, 14 strains from two outbreaks and 12 sporadic cases were classified as type O157:H7, one as O111:H-(not motility) and one as O128:H2. Typing of verotoxin by gene analysis using Polymerase Chain Reaction (PCR) showed that 9 of O157:H7 strains including two cases from outbreaks and O128:H2 have VT1 and VT2 genes, other O157:H7 have the VT2 gene and O111:H-has only the VT1 gene. Biochemical characteristic analysis indicated two strains of O157:H7 type from outbreaks were biotype II and the rest of O157:H7 were biotype I. One of the O157:H7 strain from a sporadic case showed positive for urease production. According to sensitivity tests against antibiotics, out of the O157:H7 group, one strain was resistant against ABPC, one against SM and two strains resistant to SM-TC. For plasmid profiles, all strains had 94 Kb plasmids and several smaller sizes of plasmids. But 5 strains of O157:H7 had 94 Kb plasmid only. PMID- 7876667 TI - [An outbreak of enteric adenovirus type 41 endemic in Fjieda, Japan]. AB - To determine the incidence of enteric adenovirus, 447 stool specimens were collected between January 1991 to October 1992 from children with gastroenteritis at a clinic in Fujieda, Japan. Each specimen was tested for adenovirus group antigen and for specific enteric adenovirus types 40 and 41 (Ad40/41) by using monoclonal antibody enzyme immunoassays. Adenovirus was found in 10.7% (48 of 447) cases and 77.1% (37 of 48) of them were Ad40/41. There were two peaks of adenovirus infection May and November 1991. The virus was isolated with 293 cells from 48 of adenovirus positive specimens, and then was typed according to the SmaI cleavage pattern of the viral DNA and by neutralization with specific antisera. Ad41 was predominantly isolated in 64.6% (31 of 48), and Ad40 was in 10.4% (5 of 48). The remaining virus isolates were typed as Ad1, 2, 5, and 6. Ad41 was founded in 89.3% (25 of 28) from October 1991 to March 1992. Though Sma I and Hind III cleavage identified six Ad41 variants in the period, the variants identified from October 1991 to March 1992 were only two. The results indicated two variants of Ad41 strains caused an outbreak during the end of 1991 to early 1992 in Fujieda. PMID- 7876668 TI - [Detection of Candida albicans by nested PCR]. AB - A nested PCR assay was developed for the diagnosis of Candida albicans infection. A segment of the C. albicans beta-tubulin gene was amplified in this assay that was sensitive with the detection limit of 10 fg DNA of C. albicans. This assay was found to be specific by obtaining the negative results with 13 organisms (5 other Candida, 2 Cryptococcus, 3 Aspergillus, Escherichia coli and others). Cerebrospinal fluid of a patient with C. albicans meningitis was analyzed and was found to be positive. These results suggest that this assay can be clinically useful because of its high sensitivity, specificity and rapidity. PMID- 7876669 TI - [A clinical study of respiratory infections due to mucoid Pseudomonas aeruginosa diagnosed by transtracheal aspiration]. AB - We performed a clinical study of 20 cases (33 episodes) of respiratory infections due to mucoid Pseudomonas aeruginosa by transtracheal aspiration (TTA) in the recent 10 years. There was only one pneumonia without underlying chronic lower respiratory infection (CLRTI) case positive for mucoid P. aeruginosa and others were all CLRTI among 33 TTA trials. In contrast, nonmucoid P. aeruginosa was recovered from 9 cases of respiratory infections without underlying CLRTI among 46 TTA trials. Monomicrobial infection of mucoid P. aeruginosa was 69.7%, and polymicrobial infection containing mucoid P. aeruginosa was 30.3%, and Haemophilus influenzae was the most frequent microorganism recovered with mucoid P. aeruginosa. The recovery rate of mucoid P. aeruginosa among P. aeruginosa colonized cases was 56.3% in diffuse panbronchiolitis, and that was 42.9% and 40.0% in bronchiectasis and chronic bronchitis, respectively. Mortality due to pneumonia with nonmucoid P. aeruginosa was 46.1%, but there was no fatal pneumonia case with mucoid P. aeruginosa. In CLRTI, laboratory data were not remarkably different between mucoid and non-mocoid P. aeruginosa-colonized cases. Thus, these results suggest that mucoid P. aeruginosa is a more important organism in persistent infections in the lower respiratory tract compared with nonmucoid P. aeruginosa, and further investigations is required on the mechanism and clinical role of this infection. PMID- 7876670 TI - [The role of viral infection in adults with bronchopulmonary infections]. AB - We isolated the virus from the respiratory specimens of 16 patients (7.9%) when we investigated the bronchopulmonary infections of 203 adult patients by the viral isolation method for the diagnosis of the viral infection and transtracheal aspiration (TTA) for taking directly the specimen from the lower respiratory tract. The bronchopulmonary infections, isolated the virus, consisted of acute bronchitis (3 cases), pneumonia (8 cases) and the acute exacerbation of chronic lower respiratory infection (5 cases). The positive viral isolation consisted of Rhinovirus (11 strains), Herpes simplex virus I (3 strains), Parainfluenza virus III (1 strain) and Respiratory syncytial virus (1 stain). There were 9 transtracheal aspirates, 8 pharyngeal swabs and 5 nasal washings in the positive viral specimens. We experienced 5 cases who had the same virus isolated from both the upper respiratory tract and the lower respiratory tract. H. influenzae, P. aeruginosa and other bacteria were found in 14 of the 16 TTA cultures. These results suggest that the role of the viral infection is important either independently or relating the bacterial infection in the adult bronchopulmonary infections. PMID- 7876671 TI - [Epidemiological study of the prevalence of influenza in Japan--regional differences in terms of three indices (development of epidemic outbreak, viral isolation, peak of prevalence)]. AB - The prevalence of influenza in Japan was studied, dividing the whole country into six sections such as Tohoku, Hokkaido and Kanto, to determine regional differences from the nationwide viewpoint. This study was based on data obtained from a total of 720 prefectures where three of the first index (the time the epidemic outbreak developed), second index (the time the virus was isolated) and third index (the time the prevalence reached its peak) were determined for the 16 prevalence periods of influenza between 1976 and 1993. The mean value (standard deviation) of each index was obtained for each year of prevalence and for each area. The differences obtained were analyzed statistically, and the following results were obtained: 1. There was a marked regional difference in the development of epidemic outbreak of cold; it was earliest in the Kanto and Kinki areas (late November to early December) and latest in the Kyushu area (mid January). 2. Isolation of the virus was earliest in the Kanto and Kinki area (mid January) and latest in the Chugoku and Shikoku areas (late January to early February), showing a regional difference. 3. The peak of prevalence was earliest in the Kanto area (early February) and latest in the Tohoku, Hokkaido, Chugoku and Shinkoku areas (mid February), showing a regional difference. 4. The difference between the earliest and latest areas was 4.2 weeks regarding the first index, while it was decreased to 1.8 weeks for the second index and to 0.8 weeks for the third index.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876672 TI - [Tissue gamma/delta T cells in experimental urinary tract infection relationship between other immuno-competent cells]. AB - We studied the gamma/delta T cells, which are thought to be one of the local immune-defense system, in an experimental ascending urinary tract infection model in mouse. The experimental infection was induced in the BALB/c mouse by transurethral instillation of Escherichia coli. gamma/delta T cells were stained immunohistochemically with ABC method and the localization in the uninfected and infected murine urinary tract was determined. Then, to determine the CD4 or CD8 phenotype of gamma/delta T cells in the infected site, a two-color immunohistological study was done. In the uninfected state, gamma/delta T cells were observed in the bladder epithelium and submucosa, not in the kidney. It is thought that the difference of gamma/delta T cell distribution between kidney and bladder is affected by the bacteriological milieu, because the chance for foreign antigen exposure of bladder may be greater than that of the kidney. Six hours after inoculation of E. coli, the gamma/delta T cells infiltrated in to the bladder and kidney, following a gradual increase in number. Especially at 105 days after inoculation, severe accumulation of gamma/delta T cells in the renal scarring lesion was observed. Two-color immunohistological study revealed that the phenotypes of gamma/delta T cells in the renal scarring lesion were both CD4 CD8- double negative and CD4-CD8+ single positive. The CD4-CD8+ gamma/delta T cells were probably activated by the bacterial antigen. PMID- 7876673 TI - Epidemiology studies of clinical isolates of Cryptococcus neoformans of Japan by restriction fragment length polymorphism. AB - Previous epidemiological studies of Cryptococcus neoformans infection in Japan showed that only C. neoformans var. neoformans is present and serotype A is the most common with frequencies in excess of 95%. A DNA fingerprinting method, using a genomic DNA probe (UT-4p), has become available recently which discriminates between individual isolates in a population that are morphologically and serologically indistinguishable. Fifty-two serotype A isolates of C. neoformans were obtained from three different institutions (in Nagasaki, Chiba, and Tokyo) in Japan. Only two of these strains were isolated from AIDS patients and one from pigeon excreta. Of the nine reported finger-printing patterns in serotype A, only three types (IV, V and VII) were observed in Japanese isolates. Pattern IV was almost exclusively observed in Nagasaki isolates (21/22) with only one of pattern VII. In Chiba, however, patterns VII and IV appeared to be equally distributed. In Tokyo, patterns IV and V (which included two isolates from AIDS patients) were observed at similar frequencies. Restriction fragment length polymorphism analysis of four isolates of serotype AD showed a typical serotype A pattern which also contained a serotype D-specific band. This finding suggests the independence of serotype AD. These data could enhance the survey of the epidemiology of cryptococcosis. PMID- 7876674 TI - Antibacterial activity of epigallocatechin gallate against methicillin-resistant Staphylococcus aureus. AB - The antibacterial activity of epigallocatechin gallate (EGCg), a catechin, against 53 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) was evaluated and expressed as minimal inhibitory concentration (MIC). The MIC50 and MIC90 of the strains were found be 64 and 126 micrograms/ml, respectively by the microdilution method. A time-kill study using an isolate showed that EGCg appeared to be bacteriostatic at 1-2 x MIC and bactericidal at 6 x MIC against MRSA. In addition, the activity of EGCg was stable to various physical conditions including boiling or freezing. These findings suggest that EGCg could be a useful agent for treating MRSA infection. PMID- 7876675 TI - [A case of MRSA sepsis treated by the sequential combination therapy netilmycin and minocycline]. AB - A sixteen year old female was feverish from June 12, 1993. Methicillin-resistant Staphylococcus aureus was isolated from the blood, the diagnosis of MRSA sepsis was established. Vancomycin (2 g/day) was administered for eighteen days, but MRSA was not eradicated in the blood culture. Then she was administered a combination therapy of arbekacin (200 mg/day) and imipenem/cilastain (1 g/day) for seven days, but MRSA in the blood was cultured continuously. The sequential combination therapy of netilmycin (200 mg/day) and minocycline (200 mg/day) was started, MRSA was eradicated from the blood culture after four days. The sequential combination therapy netilmycin and minocycline was seemed to be effective for MRSA infection. PMID- 7876676 TI - [A case of Corynebacterium jeikeium septicemia]. AB - We report a case of Corynebacterium jeikeium septicemia associated with malignant lymphoma. The patient is a 58-year-old male who was diagnosed as malignant lymphoma on August 1992. May 15, 1993, he was admitted to our hospital because of oliguria, abdominal flatulence and vomiting which developed a few days before admission. Anticancer regimen were started. In the middle of July, white blood cell (WBC) count dropped to 100/mm3 and body temperature rose to 39 degrees C. He was been treated with Ceftazidime and Piperacillin. C. jeikeium was recovered from blood culture. Antibiotics were switched to minocycline and vancomycin. He died of septic shock and pneumonia. Autopsy revealed the presence of the colonies of Rods. Which were morphologically compatible with C. jeikeium were observed in lung tissue and in the small pulmonary vessels. PMID- 7876677 TI - [Three interesting pediatric cases with penicillin-resistant Streptococcus pneumoniae infection]. AB - Since penicillin-resistant Streptococcus pneumoniae first recognized in 1967, the rate of penicillin-resistant strains has been increasing worldwide. There have been up to 50% from pediatric specimens in Japan. We reported three pediatric cases with penicillin G resistant Streptococcus pneumoniae infection to show some important clue from these cases for clinical practice against resistant pneumococcal infection. The first case was a typical acute mastoiditis, although we have experienced only masked mastoiditis recently. The second case was meningitis with septicemia, which did not show any abnormality in the first obtained cerebrospinal fluid. The third case was recurrent bronchitis in a child with cerebral palsy. The minimum inhibition concentrations of these isolated strains were 0.25 microgram/ml in the second case an 2.0 microgram/ml in the first and third cases. PMID- 7876678 TI - [A case report of psittacosis and chlamydial isolation from a patient]. AB - A 48-year-old female was seen at our hospital after having a severe fever of nearly 40 degrees C, for a period of 9 days. She complained of pain in the left side of her chest. An X-ray examination revealed a slight infiltration of the upper and middle lung fields. At this time, it was learned that the women's pet bird had recently died. This case was diagnosed as acute pneumonia due to psittacosis. Therefore the administration of Roxithromycin was started. After a few day her condition improved. During the course of treatment, serum was taken and a throat swab was done. A micro-immunofluorescence (MIF) test was performed to check the serum antibody levels against Chlamydia psittaci. The serum titer rose from 1:8 to 1:256 in 15 days after admission. The final diagnosis was made after positive isolation of C. psittaci by means of the cell culture method. PMID- 7876679 TI - [A child with iritis due to Chlamydia pneumoniae infection]. AB - A case of uncommon iritis due to Chlamydia pneumoniae (C. pneumoniae) is reported. The patient was a 9-year-old boy who had suffered from cough, pharyngeal pain, and low grade fever. The symptoms persisted for more than 1 month in spite of an oral cephem antibiotic. Ophthalmalgia, congestion around the iris and cough had lasted with alleviation and exacerbation. A diagnosis of C. pneumoniae infection was made by specific polymerase chain reaction (PCR) method and microimmunofluorescence test (MIF). The symptoms subsided with administration of clarithromycin (CAM: 300 mg/day) for 2 weeks. Because of the simultaneous alleviation of iritis, C. pneumoniae infection was considered to introduce the iritis. Much remains to be clarified about this pathogenesis of iritis and more detailed evaluations are required. PMID- 7876680 TI - [Investigation of (1-->3)-beta-D-glucan in sera with experimental acute pulmonary aspergillosis]. PMID- 7876681 TI - [Changes in the anti-Anisakis antibody titers in paired sera in an early period of illness]. PMID- 7876682 TI - [Bone union after lumbar postero-lateral fusion: comparative evaluation by x-ray and CT]. AB - As yet there has been no report on a uniform and precise method for evaluating bone union after lumbar postero-lateral fusion (PLF). Here we report and compare the roentgenogram (X-P) and computerized tomography (CT) methods to evaluate the union and non-union of PLF. PLF without internal fixation was undertaken in 252 patients between 1978 and 1991. Of these, 125 patients underwent both X-P and CT scanning and were followed up for more than one year (mean 4 years and 2 months, range 1 to 14 years). In the cases of complete union, X-P demonstrated that the solid fusion mass showed a continuous trabecular pattern along the grafted segment, while CT demonstrated that the solid fusion mass appeared as a long bone with the mass incorporated into the transverse process and the superior facet. In such cases, there was no micromotion on stress roentgenograms. In the cases of incomplete union, the status of the non-union was classified into three types as; Type I showing atrophy and resorption of the grafted bone, Type II showing a lack in trabecular continuity of the fusion mass, and Type III showing a gap either cranially or caudally between the fusion mass and lumbar matrix (which includes the transverse process and superior facet). X-P could easily diagnose Type I and Type II, but could not clearly diagnose Type III. CT, however, could easily diagnose Type III. Therefore, the use of only X-P might lead to a misdiagnosis in cases of Type III. The application of CT was more uniform and precise method to evaluate the state of PLF in the lumbosacral spine. PMID- 7876683 TI - Sagittal spinal flexibility in patients with idiopathic scoliosis. AB - To determine whether or not reduced sagittal spinal flexibility is associated with idiopathic scoliosis we measured the sagittal spinal flexibility in 40 normal children and in 93 children with idiopathic scoliosis. Sagittal spinal flexibility, or the range of spinal flexion (RSF), was calculated from lateral radiograms of each spine by measuring the difference in the segmental kyphotic angle between the neutral standing position and the maximally flexed position. The spines of all 40 normal children bent smoothly, but 87 of the 93 scoliosis patients had localized areas of severely decreased RSF. This striking difference in sagittal spinal flexibility between normal children and patients with idiopathic scoliosis suggested that a loss in spinal flexibility in the sagittal plane was associated with idiopathic scoliosis, and may contribute to the pathogenesis and progression of spinal curvature. PMID- 7876684 TI - [Bone mineral measurement of the calcaneus by single X-ray absorptiometry]. AB - The bone mineral content (BMC) of the calcaneus was evaluated using single X-ray absorptiometry (SXA) with respect to reproducibility of bone mineral measurement, age-related bone loss in healthy Japanese, the spine fracture threshold in osteoporotic women, and the effect of non-weight bearing on bone mass in patients after hip arthroplasty. The mean reproducibilities using this method in vitro and in vivo were 0.81% and 0.59%. In 264 healthy men aged between 21 and 79 years and 328 healthy women aged between 20 and 79 years, the calcaneus BMC reached a peak in their twenties and thereafter decreased linearly with age by 0.57% per year in men and 1.32% per year in women. Body height and weight were well correlated with the calcaneus BMC in healthy men and women (p < 0.001). The bone mineral density (BMD) of the lumbar spine was measured using dual X-ray absorptiometry (DXA) and was significantly correlated with the calcaneus BMC in both men (r = 0.727, p < 0.001) and women (r = 0.703, p < 0.001). The fracture threshold, defined as the 90th percentile for calcaneus BMC in a woman with a vertebral fracture, was 313.31 mg/cm2 and 70.2% of the peak bone mass in the calcaneus. In 30 patients with hip implant arthroplasty, the bone mass in the calcaneus, lumbar spine and the distal radius was evaluated longitudinally during a follow-up period of one year. Only the calcaneus BMC in the treated leg changed significantly during this period. In the first four months, the calcaneus BMC in the treated leg diminished by approximately 21%, but had recovered by one year after surgery. We concluded that bone mineral measurement in the calcaneus was useful for evaluating age related bone mass changes in healthy men and women, bone loss in osteoporotic patients, and the effect of non-weight bearing on bone mass in patients after hip arthroplasty. PMID- 7876685 TI - [Influence of foods on the posterior longitudinal ligament of the cervical spine and serum sex hormones]. AB - To investigate the involvement of sex hormones as a potential cause of ossification in the posterior longitudinal ligament (OPLL) of the cervical spine, we experimentally examined the influence of ingested foods on the serum levels of sex hormones and changes in the spinal ligament. Castrated rabbits were administered a sex hormone and raised with special feed. Assay of the serum sex hormone levels, analysis of the carbon and nitrogen isotope ratios in body hairs, and histological studies were carried out. In the group administered soybeans and highly concentrated saline solution, the serum estrogen level was high, the serum testosterone level was low and the delta 15N value of the body hairs was also low. Histologically, a group of newly formed chondroblasts was seen in the posterior longitudinal ligament in the angular region of a narrowed intervertebral disc, and many fibroblasts were detected by assay using a microspectrophotometer (MSP) in this group. These findings suggested that a diet high in vegetable protein, consisting mainly of beans, and foods high in salt may lead to an unbalanced state for sex hormones and cause histological changes in the spinal ligament. This, as well as other general ossifying factors of ligament, may play a role in the etiology of ossification. PMID- 7876686 TI - [Study of the effects of a new vitamin D3 derivative on type II collagen-induced arthritis in an experimental rat model of rheumatoid arthritis]. AB - The effects of a new derivative of vitamin D3, 22-oxa-1 alpha,25-dihydroxyvitamin D3 (OCT), on rheumatoid arthritis was investigated using collagen-induced arthritis in rat, as an experimental model of the disease. Peroral administration of OCT significantly suppressed the incidence of arthritis and inhibited hind-paw swelling. The levels of IgM and IgG antibodies against Type II collagen in sera were found to decrease in the OCT treated-group. The production of immunoglobulin against Type II collagen from rat spleen cells was also decreased in this group. These immunological effects of OCT on collagen-induced arthritis were more remarkable than those of 1 alpha-hydroxyvitamin D3. These findings indicated that OCT may have a therapeutic value as an immunoregulatory agent for patients with rheumatoid arthritis through inhibition of the autoimmune response to Type II collagen. PMID- 7876687 TI - [The telescoping anastomotic technique: experimental efficacy for autogenous microvessel grafting]. AB - An experimental study was performed to investigate the efficacy of the telescoping anastomotic technique for microvessel grafting. The left femoral artery was grafted into a defect in the right femoral artery in 51 rats using the telescoping technique for both the proximal and distal anastomoses. The inferior epigastric vein was grafted in situ in a further 42 rats using the same technique for both the proximal and distal anastomoses as a model of venous grafting for a venous defect. Arterial and venous grafting was performed using the conventional technique in additional rats for control purposes. The time required for anastomosis by the telescoping technique was about half that required by the conventional technique. The patency rate of the 51 arterial grafts was 51/51 (100%), and that of the 42 venous grafts was 40/42 (95.2%). In the histological examinations, the arterial grafts by the telescoping technique showed some stenosis at the site of the anastomosis at 1 week and 3 weeks postoperatively. The venous grafts, however, showed little stenosis at the site of the anastomosis at 1 and 3 weeks postoperatively. The telescoping anastomotic technique was useful for microvessel grafting and effective for saving time. PMID- 7876688 TI - [Progress in knee joint surgery]. PMID- 7876689 TI - [Progress on clinical study of hypothalamic pituitary diseases]. PMID- 7876690 TI - [Regulatory control and physiopathology of the hypothalamic pituitary system]. PMID- 7876691 TI - [Diagnostic test for hypothalamic pituitary diseases]. PMID- 7876692 TI - [Important points in diagnosis and therapy: hypothalamic syndrome]. PMID- 7876693 TI - [Important points in diagnosis and therapy: acromegaly]. PMID- 7876694 TI - [Important points in diagnosis and therapy: Cushing's syndrome]. PMID- 7876696 TI - [Important points in diagnosis and therapy: TSH producing tumor]. PMID- 7876695 TI - [Important points in diagnosis and therapy: prolactinoma]. PMID- 7876697 TI - [Important points in diagnosis and therapy: hypopituitarism]. PMID- 7876698 TI - [Important points in diagnosis and therapy: isolated ACTH deficiency]. PMID- 7876700 TI - [Important points in diagnosis and therapy: multiple endocrine neoplasia]. PMID- 7876699 TI - [Important points in diagnosis and therapy: pituitary dwarfism]. PMID- 7876701 TI - [Important points in diagnosis and therapy: diabetes insipidus]. PMID- 7876702 TI - [Important points in diagnosis and therapy: inappropriate ADH syndrome]. PMID- 7876703 TI - [Progress on diagnostic imaging of hypothalamic pituitary disorders]. PMID- 7876704 TI - [Recent progress on the surgical therapy of hypothalamic pituitary neoplasms]. PMID- 7876705 TI - [Symptoms and early diagnosis of disorders of the hypothalamic pituitary system. Discussion]. PMID- 7876706 TI - [Case of adult-onset Still's disease associated with severe liver disease and disseminated intravascular coagulation]. PMID- 7876707 TI - [Case of clonal proliferation of cells with translocation between chromosome 1 and 7 during progress of polycythemia vera]. PMID- 7876708 TI - [A case of idiopathic renal hypouricemia]. PMID- 7876709 TI - [A case of spontaneous remission in chronic B-cell leukemia with virus infection]. PMID- 7876710 TI - [Case of familial adenomatous polyposis with myelodysplastic syndrome]. PMID- 7876711 TI - [Case of arteritis syndrome with angina pectoris caused by obstructive communication between coronary artery and pulmonary artery]. PMID- 7876712 TI - [A case of lipoatrophic diabetes mellitus]. PMID- 7876713 TI - [Myocardial metabolism and radionuclide imaging]. PMID- 7876714 TI - [Anti-neutrophil cytoplasmic antibody and glomerulonephritis]. PMID- 7876715 TI - Site distribution of colonic adenomas and carcinomas in relation to colonic flexures. AB - To minimize the chance of overlooking colonic tumours, 'short segments' of the colon were defined and examined on barium enema films in relation to the distribution of colonic tumours. Films of 299 histologically proven adenomas and carcinomas from 265 consecutive patients were used. No significant differences in distribution were noted between the adenomas and carcinomas. The distance of tumours from distal minor flexures was within seven centimetres in 80% of lesions in the transverse colon, five centimetres in 80% of lesions in the descending colon, and four and six centimetres respectively for 80 and 95% of sigmoid colon lesions. In the cecum plus ascending colon 75% of the lesions were located within seven centimetres from the cecal pole. PMID- 7876716 TI - The diagnosis of anal ulcers in AIDS patients. AB - Recent reports have suggested that routine microscopic evaluation of anal ulcer tissue from AIDS patients is not the most accurate way to diagnose viral infection. This study was undertaken to determine if either viral culture (VC) or immunohistochemistry (IHC) can improve the diagnostic accuracy as compared with routine hematoxylin and eosin (H&E) staining. Specifically, we sought to identify inclusion bodies of cytomegalovirus (CMV) or herpes simplex virus (HSV) to assist in the diagnosis of CMV or HSV. All patients had clinical evidence of an anal ulcer or a nonhealing anal fissure. Duration of symptoms ranged from 1 week to 3 months with a mean of 6 weeks. All specimens were submitted for viral culture in addition to routine H&E staining; immunohistochemistry was also performed. Twenty five paraffin-embedded anal ulcer biopsies from 23 male patients (age range 27 73; mean 37.4 years) with the diagnosis of AIDS or AIDS-related complex (ARC) were reviewed over a 4 year period (1988-1992). Routine H&E staining revealed 6 (22%) specimens with CMV inclusions. Four of these 6 reacted positively with IHC (67%) and one was positive on viral culture (17%). In the remaining 19 specimens that did not reveal infection with CMV (78%), IHC was positive in 2 patients (10%) and viral culture was positive in 1 patient (5%). Although HSV was not seen in any of the specimens on H&E staining, IHC was positive in one patient (3.5%) and viral culture reacted positively in 8 (29%) specimens. Thus IHC is a good confirmatory test for CMV inclusions and can be used to achieve a definitive diagnosis in equivocal cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876717 TI - Hemorrhoidal bleeding in chronic spinal cord injury: results of multiple banding. AB - Most patients with chronic spinal cord injury (SCI) have hemorrhoidal bleeding. 87 banding procedures were performed for bleeding on 62 men with chronic SCI. Multiple bands per session were routinely necessary. Bleeding sites at or distal to the dentate line were also banded. There were no major complications. An outcome questionnaire was completed by 60 subjects (97%). Mean follow-up was one year, minimum one-half year. 73% of patients reported significant reduction in bleeding post-banding, and 20% reported some reduction. A majority of patients felt the procedure was useful or worthwhile overall. Absent sensation allows banding of external hemorrhoids, although symptoms of autonomic hyper-reflexia may occur in patients with lesions at T6 or above. Multiple banding is a safe and effective treatment for hemorrhoidal bleeding in SCI. PMID- 7876718 TI - Management of Peutz-Jeghers syndrome. Experience with patients from the Danish Polyposis Register. AB - Danish patients with Peutz-Jeghers syndrome are registered in the Danish Polyposis Register. We have initiated a new follow-up programme based on recent literature including our own cases. This has been adjusted to the regrowth rate of the polyps whereby patients with no symptoms and low regrowth rate are followed with few examinations. The programme includes upper and lower gastrointestinal endoscopy, small bowel enema and in cases with large or symptomatic polyps, laparotomy with intraoperative total enteroscopy with polypectomy as required. Pelvic examination, cervical smear, breast and testicular examination are carried out after the age of 30 years. PMID- 7876719 TI - Non-polypoid adenoma of the large intestine. AB - In order to find non-polypoid (flat) adenomas in the large intestine, one hundred and twenty-six consecutively resected large bowels were stained with methylene blue or haematoxylin and examined using a stereoscopic microscope with special attention to pit pattern abnormalities. The primary diseases were classified into familial adenomatous polyposis (FAP) in 9 cases, multiple adenomas in 2 cases, colorectal cancers in 90 cases, Crohn's disease in 5 cases, ulcerative colitis in 2 cases, constipation in 9 cases, diverticular disease in 3 cases and others in 6 cases, respectively. Thirty-five flat adenomas were detected in 14 colons (14/126 = 11%). Twenty-one flat adenomas were found in 9 non-FAP cases (7 colons removed for cancer and 2 for multiple adenomas) and the remaining 14 flat adenomas were found in 5 FAP colons. No flat adenomas were found in any of the 25 colons removed for non-neoplastic disease. Nine flat adenomas (26%) had a depressed shape. The mean age of the non-FAP cases was 57 years and that of the FAP cases was 29 years (P < 0.005). The mean size of non-FAP flat adenomas was 6.1 mm and that of FAP flat adenomas was 3.1 mm (P < 0.005). Non-FAP flat adenomas were more frequently right-sided than those in FAP. Epithelial dysplasia was graded as mild in 31 (89%) and moderate in 4 (11%), respectively. Moderate dysplasia was found in non-FAP cases exclusively. These results suggest that flat adenomas may be heterogeneous. The significance of these lesions is discussed. PMID- 7876720 TI - The electrically stimulated (dynamic) graciloplasty for faecal incontinence- first experiences with a modified muscle sling. AB - Continence following the gracilis stimulated neosphincter reconstruction after total rectal excision is inferior to that obtained in the presence of an intact anal canal. We describe a modification of the alpha loop in which the tendon is brought through the belly of the gracilis muscle. The results in three patients are presented. PMID- 7876721 TI - Secondary surgery after failed postanal or anterior sphincter repair. AB - Secondary surgery after failed postanal repair or anterior sphincter repair was performed in eight female patients. After failed postanal repair in five patients, anterior sphincter plication and levatorplasty was the secondary procedure. In two patients a defect of the anterior external sphincter was corrected and in two patients an extremely thin external sphincter was augmented. This contributed to an excellent result in three and a good result in one patient. No improvement was achieved in one patient without anterior defect. After failed anterior sphincter repair in three patients, postanal repair was the secondary procedure. A good result was obtained in one patient and failure in two. Secondary surgery failed postanal or anterior sphincter repair may have a good result in the majority of patients. PMID- 7876722 TI - The role of congenital hypertrophy of the retinal pigment epithelium in screening for familial adenomatous polyposis. AB - Retinal examination by indirect ophthalmoscopy was performed on seventy members from 20 kindreds demonstrating the clinical manifestations of familial adenomatous polyposis and forty controls. Thirty-four of 43 affected patients manifested CHRPE lesions compared with 2 of 27 at risk and 2 of 40 controls giving a sensitivity of 79% and specificity of 95% based on the control group. The difference between the affected and at risk groups was significant (Chi squared = 34.098, 1 df, P = 0.001). The low sensitivity and variation in incidence of CHRPE in FAP patients and general population documented in the world literature prevent its use as a sole marker for the condition. With advances in knowledge of the disease at a molecular level it is now possible to alter risks for families by DNA analysis. There remain a number of patients in whom such techniques do not significantly alter risks. In these families by combining the results of DNA analysis, sigmoidoscopy and retinal examination it may be possible to alter risks by a significant degree. Retinal examination should be reserved for those families in whom risks cannot be altered sufficiently by DNA analysis alone. PMID- 7876723 TI - Surface versus needle electrodes in determination of motor conduction time to the external anal sphincter. AB - Patients were referred to our neurophysiological department in order to investigate anorectal function. By the means of magnetic stimulation the total motor conduction can be determined. Only patients with normal latency of the pudendal nerve and normal EMG of the external anal sphincter were examined. Stimulation was carried out above the motor cortex with a MO between 80 and 100%. The recording was carried out in 22 patients with concentric needle electrodes and in the other 18 patients with surface electrodes. The mean latency in the group with surface electrodes was 19.4 ms (SD 1.7), and in the group with needle electrodes 23.4 ms (SD 4). Our results suggest, that in magnetic stimulation above the motor cortex and recording with a concentric needle electrode, the range and the mean was higher than with surface electrodes. In our opinion surface electrodes are preferable to needle electrodes in determining motor conduction time to the external anal sphincter. PMID- 7876724 TI - Treatment of pilonidal sinuses by phenol injections. AB - Six female and 39 male outpatients, who suffered from acutely inflamed pilonidal sinus were treated by sclerotherapy between January 1985 and December 1988. Under local anaesthesia, 1-2 ml 80% phenol was injected into the sinus. The phenol, which was allowed to act for a minute, was washed out by irrigating the sinus with physiological common-salt solution. Of the questionnaire sent to all 45 patients, 37 proved suitable for evaluation. Complete healing occurred in 22 cases (59.8%). The healing time was 6.2 weeks on average. Besides a rather frequently observed transient reddening as a result of the local inflammation caused by the phenol, 5 patients developed an abcess which needed operative treatment. This study does not support the encouraging results of previous series. PMID- 7876725 TI - The relationship between tumour volume and the extent of spread in colorectal carcinoma. AB - 115 colorectal carcinomas were measured in three dimensions. To compare the tumour volume, greatest linear dimension and the maximum thickness of colorectal carcinomas with the extent of spread. A formula was devised for estimating tumour volume based on the oval shape of most carcinomas. Dukes staging was performed after xylene/alcohol fat clearance. The mean tumour volume of Dukes B tumours was greater than A tumours. The mean volume of C tumours was greater than that of A tumours. The mean volume of Dukes B tumours was greater than that of C tumours. The greatest linear dimension and the tumour thickness measurements also showed differences but were not as discriminating as the tumour volume. Using the Astler and Coller modification of Dukes staging, the mean tumour volume of C2 tumours was significantly greater than that of C1 tumours. Both C1 and C2 tumour volumes when considered separately were smaller than those of the B tumours. There was a significant positive correlation coefficient between tumour volume and the greatest linear dimension and also between tumour volume and the tumour thickness. There was no significant correlation within the C tumours between tumour volume and the number of lymph nodes with metastatic deposits. Colorectal carcinomas differ from other solid tumours in their growth pattern and metastatic behaviour. There is no direct relationship between increasing tumour size and progression in the Dukes staging. Some tumours appear to metastasize to lymph nodes while still small (C1 tumours); other tumours appear not to metastasize to lymph nodes regardless of size (B tumours).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876726 TI - Alteration of maximum anal resting pressure by digital rectal examination prior to manometry: analysis of agreement between repeat measurements. AB - To study whether digital examination preceding anal manometry causes significant alteration of maximum resting pressure reading and to quantify the discrepancies, 78 individuals (64 incontinent, 14 controls) were investigated. Recordings of maximum resting pressure were taken before and after digital rectal examination. There was a mean discrepancy of only -1.8 cms H2O between the readings and excellent correlation, but analysis of agreement revealed a bias that tended to be greater with smaller measurements and unacceptable variability between test results. Furthermore, the bias was not related to age, gender, the grade of incontinence, maximum voluntary contraction, functional anal canal length and threshold volume. Digital rectal examination prior to manometry causes unpredictable results especially in patients with lower maximum resting pressures and should strictly be avoided. PMID- 7876727 TI - Left-sided colon and colorectal anastomoses: Doppler ultrasound as an aid to assess bowel vascularization. A prospective evaluation of 200 consecutive elective cases. AB - Two hundred non-randomized left-sided colon and colorectal anastomoses were performed on 199 consecutive patients admitted over a 4-year period (107 men and 92 woman with a median age of 66 years). There were 117 high anastomoses (above the peritoneal reflection), 86 (74%) of which were hand sewn, and 83 low anastomoses, 78 (94%) stapled with an EEA instrument. Adequate blood supply was assessed with a Doppler ultrasound in all but 5 cases. In ten patients bowel edges to be anastomosed were recut because of a negative Doppler ultrasound reading. One hundred and eighty-nine anastomoses were radiologically controlled. In-hospital post-operative mortality was 2.5% and morbidity 20%. There were two (1%) clinical anastomotic leaks and three (1.5%) radiological leaks. Use of Doppler ultrasound is simple and safe to assess vascularization of the intestinal edges. It may have contributed to the low anastomotic complication rate observed in this series. PMID- 7876728 TI - An old head on new shoulders. AB - A modified stapling technique for anterior resection is described. A pursestring suture is placed in the proximal colon after resection of the specimen; the head of a stapling gun is detached from the stapler and inserted into the proximal bowel and the pursestring suture is tied. A pursestring suture is placed in the rectal stump. A stapling device head from a previous case is autoclaved and then fitted to the stapling device to allow safe insertion per anum: this head is discarded as soon as the distal pursestring is tied. The anastomosis is then completed in the usual way. This technique has been used successfully in twenty one cases with minimal morbidity and no mortality. PMID- 7876729 TI - The Emperor who smoked a pipe. AB - Since 1946 authoritative reports have identified smoking as a cause of cancer of the lung and a probable cause of cancer of the larynx. Crown Prince Frederick (later Emperor Frederick III of Prussia and the German Kaiser) was a pipe smoker for at least 30 years before he died of cancer of the larynx in 1888 at the age of 57 years. The evidence is so overwhelming that this author proposes that the Emperor's laryngeal cancer was induced by tobacco. PMID- 7876730 TI - Subcutaneous tissue reaction to synthetic auditory ossicle (Apaceram) in rats. AB - A study was carried out in order to obtain further information about the soft tissue response to thin Apaceram discs of dense hydroxyapatite (HA) implanted in rats for various periods of time between one day and 10 months. The Apaceram discs were implanted subcutaneously into the interscapular region of 33 rats. A sham operation was performed on eight rats used as controls. Decalcified histological sections stained with haematoxylin and eosin and Mallory's azan were examined and the different cell types found around the implants were counted. It was found that an acute inflammatory reaction occurred after one day and disappeared at about two weeks after implantation. In the test groups, macrophages and lymphocytes disappeared about one week later, and no inflammatory reaction was observed from one to three months. However, a tissue reaction occurred at six months with the appearance of macrophages and lymphocytes, and decreased gradually at 10 months. Meanwhile, a few foreign body giant cells at the Apaceram-tissue interface and a thick layer of fibrous connective tissue around the Apaceram disc were observed at 10 months. No osteogenesis was observed in any specimen. The results obtained so far suggest that Apaceram is still a useful material for reconstructive surgery, despite the possible appearance of a slight macrophage reaction at six months. PMID- 7876731 TI - The effect of long-term antibiotic therapy upon ciliary beat frequency in chronic rhinosinusitis. AB - The mucociliary escalator is the first line of defence of the upper and lower respiratory tracts (Greenstone and Cole, 1985; Sleigh et al., 1988). Failure of mucociliary clearance is associated with chronic or recurrent respiratory tract infection. Ten patients with chronic rhinosinusitis underwent nasal brushings for the assessment of ciliary beat frequency. In two no beating cilia were seen; in the remainder the mean value was 9.3 Hz +/- 2.3; range 6.1-12.8 Hz (n = 8). Following three months continuous oral antibiotic therapy repeat nasal brushings demonstrated increased ciliary beat frequencies in all patients, mean value 13.7 Hz +/- 1.6; range 11.5-16.3 Hz (n = 10); (p < 0.01; paired t-test). Depression of mucociliary clearance can occur secondarily to chronic infection and is improved by prolonged antibiotics. PMID- 7876732 TI - The diagnosis of inflammatory sinonasal disease. AB - A prospective study was carried out on 25 consecutive patients referred to an outpatient clinic at The Royal National Throat, Nose and Ear Hospital, with a medical letter suggestive of sinusitis, to test the hypothesis that the diagnosis of inflammatory sinus disease could be made simply and accurately by employing systematic nasal endoscopy and a series of plain sinus X-rays. The study compared the diagnostic yields of the history, rigid nasal endoscopy and plain sinus films with computed tomography. All the investigations were performed on the same day. The interobserver variability between consultant ENT surgeon, senior registrar and registrar were compared. With heightened concern over the radiation exposure patients are receiving for medical investigations, the radiation exposure was determined for a selected group of patients. This study demonstrated that in the diagnosis of inflammatory sinonasal disease the clinical assessment correlated with the CT findings in over 90 per cent of cases. This accuracy was dependent on the experience of the clinician in using rigid nasal endoscopy. Interobserver variability ranged from 71 to 90.4 per cent in the correct diagnosis of underlying sinus disease. Close agreement was seen with the interpretation of CT scans. The concordance rate between plain films and CT scans was 87 per cent when reported by a consultant radiologist. This is in close agreement with previously reported studies. The average radiation exposure of coronal CT scanning was 218 times the dose for plain sinus X-rays. PMID- 7876733 TI - Endoscopic fenestration of choanal atresia. AB - We report two cases of unilateral choanal atresia and one of choanal stenosis treated successfully by endoscopic fenestration, with no recurrence at a mean follow-up of 18 months. Rigid endoscopy and axial CT scanning confirm the clinical diagnosis and this technique avoids the need for stenting or prolonged post-operative stay. PMID- 7876734 TI - Efficacy of fine needle aspiration cytology in the diagnosis of tuberculosis of the thyroid gland: a study of 18 cases. AB - Tuberculosis of the thyroid gland is an extremely rare condition. Amongst 1565 cases of thyroid lesions subjected to fine needle aspiration cytology (FNAC) over a period of nine years, 18 cases (1.15 per cent) were found to have cytological features consistent with tuberculosis thyroiditis. Acid-fast bacilli were isolated in all cases. The ages of the patients ranged from 36 to 52 years with a median age of 46 years: there were 12 females and 6 males. All the patients presented with painless solitary nodules of the thyroid. Three patients had concomitant cervical lympadenopathy and four patients were known to have tuberculosis of the lungs which was being treated. Solitary nodules of the thyroid were confirmed by a thyroid scan with radioactive iodine. Fine needle aspirates from thyroid swellings showed epithelioid granulomas with necrosis in all cases. There were no false reports or complications. It is evident from this study that FNAC is an efficient way with which to detect tuberculosis of the thyroid gland. PMID- 7876735 TI - Expression of Fos-protein activated by tactile stimulation on the laryngeal vestibulum in the cat's lower brain stem. AB - To demonstrate morphologically the neurons participating in the laryngeal reflex, Fos-expression, activated with tactile stimulation of the laryngeal vestibulum, was mapped in the cat's lower brain stem utilizing immunohistochemistry. In the stimulation group, many Fos-immunoreactive (ir) neurons were recognized in the nucleus tractus solitarii (NTS) from the level of the most rostral portion of the dorsal motor nucleus of the vagus to the level of the most caudal portion of the inferior olivary nucleus (IO), and in the nucleus ambiguus (NA) from the level of the rostral end of the hypoglossal nucleus to the level of the caudal end of the IO, bilaterally. While some Fos-ir cells were found in the spinal nucleus of the trigeminus, they were also found in the reticular nuclei bilaterally. In the control group, Fos-ir cells were distinctly fewer in number than those in the stimulation group. The results suggested that in the brain stem, the laryngeal reflex pathways have more than two synaptic relays through the interneurons in between the NTS and the NA. PMID- 7876736 TI - Salvage brachytherapy and salvage surgery for recurrent oropharyngeal carcinoma following radiotherapy. AB - We reviewed 21 patients who underwent salvage treatment after a biopsy of proven locally recurrent carcinoma of the oropharynx. Two of these patients underwent a second salvage treatment after failure of the first. Treatment was performed with Ir192 interstitial implant in 17 cases (13 rT1 and 4 rT2); by surgery in five cases (3 rT1, 1 rT2, 1 rTx), including two patients who had relapsed after salvage treatment with Ir192 implant; and by hyperfractionated external beam irradiation plus concomitant Tegafur chemotherapy in one case (rT3). The primary tumour was controlled in four of the 17 cases (23 per cent) treated with Ir192 implant. Of these four patients, two remained disease-free 42 and 59 months after treatment, one died of nodal metastases eight months after treatment and another of distant metastases 19 months after treatment. Four of the five cases (80 per cent) treated with surgery, including two patients who relapsed after salvage brachytherapy, remained free from local, regional and distant relapse 21, 25, 31 and 56 months after treatment. PMID- 7876737 TI - Anterior cervical pain syndromes: hyoid, thyroid and cricoid cartilage syndromes and their treatment with triamcinolone acetonide. AB - Fifty-one patients who presented with anterior cervical or throat pain, without apparent cause, were selected for study at the ENT outpatient department from January 1987 to January 1992. Their clinical symptoms, probable aetiologies and treatment were studied. The most common diagnosis was hyoid syndrome, followed by thyroid cartilage syndrome and cricoid cartilage syndrome. These last two syndromes have not been previously reported because they were coined in Ramathibodi Hospital for patients who had similar clinical patterns localized to the thyroid and cricoid cartilages respectively. Treatment using intralesional triamcinolone acetonide injection was effective in all cases. There was no recurrence after one-five years follow-up. PMID- 7876738 TI - Mycobacterium marches back. AB - The resurgence of tuberculosis world-wide and its association with HIV infection means a greater likelihood of otolaryngologists encountering the disease in one form or another. In this review the features of primary and secondary tuberculosis in various head and neck sites are described, and recent advances in diagnosis are discussed. For the otolaryngologists other important aspects such as infections with atypical mycobacteria, the differential diagnosis of cervical lymphadenopathy in HIV-infected patients, recently recognized problems in drug treatment, and the role of surgery in head and neck tuberculosis are also discussed. PMID- 7876739 TI - Cordectomy: a solution to Teflon granuloma of the vocal fold. AB - Teflon injection has been widely used for the treatment of unilateral vocal fold paralysis. Complications are few and infrequent. Overinjection and Teflon granuloma are the two commonest problems encountered. Treating such complications and restoring vocal quality is widely regarded as difficult. Endoscopic transmucosal excision of the excess Teflon and/or granuloma has not been successful in improving phonatory quality. Cordectomy is proposed as an alternative surgical approach for managing both the convex vocal fold and Teflon granuloma after injection. PMID- 7876740 TI - Delayed extrusion of a cochlear implant: a case report of an implant extruding 21 months after the original operation. AB - We present a case report of a lady who received a Nucleus 22 Channel cochlear implant in July, 1992. She presented again in April, 1994 when the cochlear implant had extruded spontaneously. The possible aetiology of this extrusion, as well as the technique of surgical management, is discussed. PMID- 7876741 TI - Neonatal upper airway obstruction caused by chlamydial rhinitis. PMID- 7876742 TI - Palatal myoclonus affected by neck position. AB - Palatal myoclonus is defined as a continuous, rhythmic contraction of the palatal musculature. Reverberant neuronal activity in a region of the brain stem known as the Guillain-Mollaret triangle is believed to underlie this condition. We present a case of palatal myoclonus which could be abolished by anterior neck flexion. The pathology and management of this condition is briefly discussed. PMID- 7876743 TI - Glomus tumour of the oropharynx. AB - Haemangiopericytoma and glomus tumours are infrequent neoplasms in otorrhinolaryngology. A case of glomus tumour with haemangiopericytomatous features of the left amygdalar fossa is reported. Its clinical, surgical and histological features are described. This case report supports the unitary concept of smooth muscle tumours of the small vascular wall. PMID- 7876744 TI - Submandibular salivary disease: a proposed allergic aetiology. AB - Two cases of submandibular gland swelling are documented. In one patient examination of the excised submandibular gland revealed a dense eosinophilia: the other patient had a peripheral blood eosinophilia. Both patients demonstrated a marked decrease in the swelling of the salivary glands after a course of oral antihistamine. Although allergy has been implicated as a cause of recurrent parotid gland swelling, there are no previous reports of such a phenomenon occurring in the submandibular gland. PMID- 7876746 TI - Mycobacterium avium-intracellulare cervical lymphadenitis in siblings: a case report and review. AB - We report two cases of cervical mycobacterium avium-intracellulare lymphadenitis in siblings which developed within one month of each other. There was no underlying immunodeficiency but the children lived in close proximity to a pigeon loft. PMID- 7876745 TI - Aerodigestive tract obstruction as a late complication of radiotherapy. AB - Oedema, fibrosis, and stenosis of the hypopharynx and the oesophageal inlet are described in a few publications as a complication of post-laryngectomy irradiation treatment. In this paper a case of laryngeal carcinoma, treated exclusively by irradiation, where severe laryngeal and hypopharyngeal stenosis with complete occlusion of the oesophageal inlet were manifested as a late complication is described. We have found no similar case described in the English literature. PMID- 7876748 TI - Smooth muscle tumours of the larynx. AB - Two cases of laryngeal smooth muscle tumours are reported: one a benign leiomyoma, the other a malignant leiomyosarcoma. These tumours may present diagnostic difficulties and immunocytochemistry is helpful in distinguishing smooth muscle tumours from other connective tissue neoplasms and spindle cell squamous carcinoma. Primary treatment in both cases should be surgical resection with small (T1, T2) malignant tumours suitable for partial laryngectomy. Postoperative radiotherapy may have a role in allowing a more limited surgical resection. PMID- 7876747 TI - Amplification of the Int-2 gene in head and neck squamous cell carcinoma. AB - Cellular oncogenes have been implicated in head and neck cancer development since 1986. More recently interest has focused on chromosome 11q13; oncogenes therein undergoing ongoing investigation include Bcl-1/Prad-1, Hst-1 and Int-2. Our laboratory has studied the Int-2 oncogene for several years, primarily in the breast. This paper presents our investigations of Int-2 in the head and neck. Thirty-four paraffin-embedded primary squamous cell carcinomas were studied for Int-2 gene amplification using a carefully controlled method of sequence quantification by DNA dot blots. Amplification, mostly low level, was identified in 62 per cent of samples studied. No clinical correlation to amplification could be found. Further studies are underway looking for evidence of expression of Int 2 in fresh tissues and for amplification and expression of other oncogenes on this amplicon. PMID- 7876749 TI - Post-radiation primary intranodal leiomyosarcoma. AB - An unusual case of post-radiation primary intranodal leiomyosarcoma of the cervical lymph node is presented. The patient was a 32-year-old white man who was treated in 1986 with hemiglossectomy and right neck dissection, followed by radiation therapy, for squamous cell carcinoma of the tongue. Six years later, he presented with an enlarged left cervical lymph node which on biopsy showed a high grade spindle cell malignant neoplasm. Immunohistochemistry and electron microscopic study verified the smooth muscle origin of the tumour. Extensive work up for a second primary lesion was negative. Primary intranodal leiomyosarcoma is extremely rare. We briefly discuss the histological differential diagnosis of spindle cell lesions of lymph nodes, leiomyosarcoma of the vessel wall and radiation-associated sarcoma. PMID- 7876750 TI - Evaluation of a new direct radioimmunoassay for serum thyroid peroxidase and thyroglobulin antibodies. AB - The measurement of serum TPO Ab and Tg Ab by a new direct sensitive RIA in this study are quantitative and provided a convenient system. When compared to the commonly used PH technique for TM Ab and Tg Ab, this RIA determination appears to be more sensitive than by PH, since it enabled detection of TPO Ab and/or Tg Ab in sera that were negative by PH. Thus, this RIA determination should be more widely used in a clinical laboratory. PMID- 7876751 TI - Iliotibial band for anterior cruciate ligament reconstruction: a new technique for graft augmentation, placement and fixation. AB - A simple surgical technique to reconstruct the ACL deficient knee was described. A strip of ITB and fascia lata augmented by degradable suture materials was used as the substitute. The strip was introduced into the isometric area of the original ACL attachment through a drill hole made in the lateral femoral condyle. Drilling was guided by the anatomical landmarks without using special device. The graft was then rigidly fixed to the tibia by intraosseous compression, the method previously described by the author. Clinical results were assessed by both subjective symptoms and physical examinations. In 33 patients followed-up for an average of 34.1 months, thirty of them who were chronic cases had few or no symptoms concerning pain, swelling, laxity and stiffness at the last visit. Lachman test, anterior drawer and Slocum test were negative in 87.92, 81.87 and 100 per cent respectively. This technique requires only basic instruments and skill, and is thus generalizable to institutions having limited surgical facilities. PMID- 7876752 TI - Predictors of bronchodilator responsiveness in infants with wheezing associated respiratory tract infection. AB - The responsiveness to bronchodilator is variable in infants with wheezing associated respiratory illness (WARI). Factors for prediction of the response will lead to more rational use of the bronchodilator in these infants. We examined the possible predictive factors in 44 children under 2 years of age who had their first episode of WARI. All of them were treated with 0.15 mg/kg of nebulized salbutamol. Thirty patients (68%) with decreasing clinical score > or = 3 after treatment were considered as the responders while the remainder (14 infants) were non responders. By using Chi-square test, Fisher exact test and Mann-Whitney U test to compare the data of the 2 groups, the significant factors for the responders were older than 6 months and history of previous LRI (p < 0.01). The significant factors for the non-responders included concurrent diarrhea, patchy pulmonary infiltration and positive RSV in the nasopharyngeal secretion (p < 0.01). These results suggested effective bronchodilator therapy in infants older than 6 months or having a history of previous LRI. Those who had acute RSV infection or patchy infiltration in chest X-ray and associated diarrhea were less likely to respond. PMID- 7876753 TI - Efficacy of common broad spectrum anthelmintics against hook worm, Ascaris and Trichiuris in Hat Yai district, Songkhla Province, Thailand. AB - 1. The third therapeutic scheme should be used in the hospital. 2. The second and third therapeutic scheme may be used in mass treatment. 3. The 4th-6th therapeutic scheme is to be considered, reviewed, and evaluated. 4. Model and technology of permanent worms control is to be studied. 5. The treatment and control of Ascaris were simple. Cure with low reinfection rate and long reinfection period was remarkable. 6. The prevalence rate and reinfection rate of Trichiuris was high, and not so sensitive to any antelmintics. 7. The reinfection rate in the second group was not superior to the first group and the third group. This revealed no effectiveness of ovicidal and larvicidal on the helminthiasis. 8. Reinfection rate in the third therapeutic scheme was the least group. 9. Toxicity and side effect were not found in any anthelmintics. 10. Broad Spectrum Anthelmintics are necessary in mass treatment or blind treatment. PMID- 7876754 TI - Prevalence of drug resistance in Thai human immunodeficiency virus seropositive tuberculosis patients. AB - The emergence of drug resistant tuberculosis has been reported from many countries which have had epidemics of human immunodeficiency virus (HIV) infection. This study was conducted at the Central Chest Hospital, Thailand in order to determine the prevalence of drug resistance before treatment in Thai HIV infected tuberculosis patients. From the Statistics and Registration Unit, pulmonary tuberculosis patients with HIV seropositivity were matched in terms of age and gender with control cases who attended the tuberculosis clinic on the same day. Results of sensitivity test were obtained from record cards in the Microbiology Section. The method for determining the sensitivity test was absolute concentration. During the study period from January 1988 to December 1993, 798 patients were registered as having tuberculosis and HIV infection. Only 406 sensitivity tests were available before treatment and resisted to Isoniazid 56 (13.8%), rifampicin 36 (8.9%), ethambutol 6 (1.5%), streptomycin 64 (15.8%) and Multidrug resistant (MDR)- TB 11 (2.7%). In the control group, 475 tests were available and resisted to isoniazid 61 (12.8%), rifampicin 52 (10.9%), ethambutal 2 (0.4%), streptomycin 46 (9.7%) and MDR-TB 13 (2.7%). The prevalence of resistance to each drug was not significantly different except for streptomycin. We concluded that the prevalence of antituberculous drug resistance among Thai HIV-infected tuberculosis patients was not higher than among general tuberculosis patients. PMID- 7876755 TI - Maternal and umbilical cord blood lead levels in Ramathibodi Hospital, 1993. AB - A prospective cross-sectional study of maternal and umbilical cord blood lead levels was conducted in a total of 500 deliveries at Ramathibodi Hospital. The mean concentrations of lead in maternal and cord blood were 6.2 +/- 2.0, 1.6 +/- 0.5 microgram/dl respectively. There was direct relationship between maternal and umbilical cord blood lead level. Maternal occupation and length of stay in Bangkok were related to maternal blood lead levels. There was no association between adverse pregnancy outcomes and maternal blood lead levels. A large scale study and periodic surveillance of blood lead levels in pregnancy is advocated. PMID- 7876756 TI - Accuracy of ultrasonic fetal weight estimation: a comparison of three equations employed for estimating fetal weight. AB - This study was conducted to compare the accuracy in estimating the fetal weight of three equations with ultrasound in 104 pregnant women. Equation I log 10 (EFW) = 1.85479 + 0.09008 (BPD) + 0.02466 (AC) Equation II log 10 (EFW) = 2.24784 + 0.09122 (FL) + 0.002798 (BPD x AC) -0.0010112 (AC x FL) Equation III log 10 (EFW) = -1.7492 + 0.166 (BPD) + 0.046 (AC) - 2.646 (AC x BPD)/1000 There was no difference in either the overall mean errors of 95 per cent CI among the three equations, except in the least error for equation II in these with birthweight of less than 2,000 grams and for equation III in these with birthweight of more than 3,000 grams. It was concluded, therefore, that predictions based on either equation I or II developed from local Thai population, which have an almost identical overall mean error when compared with one another or with Shepard's (i.e. equation III), can be used in our clinical. PMID- 7876757 TI - Prevalence and connotative meaning of cigarette smoking among Thai adolescents and young adults. AB - Prevalence and evaluative opinions about smoking among 527 adolescents and young adults were quantified in order to assess the efficacy of Thailand's mass media antismoking campaign. The reactions of subjects to the smoking of (a) father, (b) mother, (c) boys, (d) girls, and (e) myself were obtained using a semantic differential measure. Virtually all subjects had seen antismoking adds on television and the overall perception of smoking was highly disapproving with significant gender and age differences being present. Older males were more likely to smoke and had less critical attitudes about this harmful behavior than their younger peers and female participants. Reactions to female smoking (mother and girls) were more derogatory than to the same behavior among males (father and boys). Results suggest that smoking will continue as a serious problem among Thai males and demonstrate the addictive nature of cigarette smoking which persists in spite of the increasingly negative evaluative attitudes of users. PMID- 7876758 TI - Elective hysterectomy--trends at Angthong Hospital. AB - From October 1988 to September 1992, 240 women in Angthong Hospital had elective hysterectomy. Myoma uteri was found as the first leading indication representing 47.9 per cent. Genital prolapse was the second (20.4%), and endometriosis was the third (14.2%). Elective hysterectomy was also performed in benign ovarian tumors (8.3%), dysfunctional uterine bleeding (6.3%) and chronic PID (2.9%). Emergency hysterectomy for obstetrical and gynaecological issues accounted for 2.0 per cent and 1.6 per cent respectively. Most hysterectomies (39.2%) were performed on women aged between 40 and 49 years. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was also the first leading type of surgery (52.5%). No serious intraoperative or postoperative complications were found. The study showed satisfactory results for evaluation of the new trends of hysterectomy and the achievement of the goal in developing the hospital potential to be the best general hospital for tertiary care and as the center for referral patients in Obstetrics and Gynaecology from nearby general and community hospitals. PMID- 7876759 TI - Pseudocyst mass at neck: complication after tracheostomy. AB - Neck mass after the tracheostomy is a rare complication. A case report of pseudocyst at the left paratracheal area was presented and this has not yet been reported in the English literature. We proposed the pathophysiology of this condition and prevention methods. PMID- 7876760 TI - The role of radiation therapy in retinoblastoma. AB - Retinoblastoma is the most common eye malignancy in Southeast Asia. In the early stage of the disease, photocoagulation, cryotherapy combined with chemotherapy and radiation therapy not only preserve vision but also preserve life. In advanced cases, the patient almost always refuses treatment when they are told to have enucleation and this leads them to more severe disease with distant metastasis. Nevertheless, even in such a poor condition, this report has shown several cases with very poor prognostic factors but effective radiation, chemotherapy after surgery still provided a very good outcome. Thus, the public should be educated that this disease can be cured even in the advanced stage. Early detection for the sake of vision and quality of life is the future intent. In the near future, it is hoped that fewer patients will refuse treatment or be lost to follow-up because of their ignorance and poverty. PMID- 7876761 TI - Hormonal and metabolic responses to acute exercise in Thai women. AB - Physiological and hormonal changes after acute exercise of moderate intensity (75% VO2 max) by pedalling bicycle ergometer were studied during follicular and/or luteal phase of menstrual cycle in sixteen healthy Thai women compared to the other sixteen non-exercised women. Physiological recordings and hormonal determinations were performed at corresponding times as follows: before, immediately after and 30 minutes after stopping exercise. Exercise significantly increased lactic acid, pulse rate, respiratory rate, systolic and mean arterial blood pressure and decreased plasma glucose while diastolic blood pressure, hemoglobin and hematocrit were not significantly changed. Plasma LH, FSH and estradiol were unaffected by exercise either in follicular or luteal phase. Plasma progesterone and cortisol rose in response to acute exercise during luteal and follicular phase respectively. Testosterone and prolactin concentrations in blood decreased significantly 30 minutes after exercise during the luteal phase. The effects of acute exercise on studied hormones related to reproductive function in women were discussed. PMID- 7876762 TI - Dengue infection with unusual manifestations. AB - In 1987, 505 serologically confirmed dengue infection patients were admitted to the Department of Pediatrics, Chulalongkorn Hospital, Bangkok, Thailand. Fourteen patients had unusual manifestations which were mostly encephalopathic and hepatopathic. Patients who had unusual manifestations tended to be in the younger age group and had higher mortality. PMID- 7876763 TI - Detection of human cytomegalovirus in urine of infants by polymerase chain reaction. AB - Polymerase chain reaction (PCR), viral isolation and serological methods were used to diagnose HCMV infection in infants. Specimens of urine and clotted blood were collected from suspected cases of congenital or HCMV infection who attended the Pediatric Clinic, Siriraj Hospital. Prevalence of HCMV infection was found in 3 per cent of infants aged under 14 days and increased to 48 per cent in infants aged over 14 days. PCR was the most sensitive technique, it could detect HCMV infection in 29 per cent of the study infants, whereas, detection rate by isolation was 17 per cent and by specific IgM ELISA was 15 per cent. Sensitivity and specificity of PCR compared with isolation and/or serology were 93 per cent and 96 per cent, respectively. Detection of HCMV in urine by PCR can be used as a sensitive and rapid test for diagnosis of HCMV infection in infants. PMID- 7876764 TI - Treatment of hydroceles by aspirations and tetracycline instillations. AB - In conclusion, tetracycline hydrochloride is an effective and safe sclerosant for the treatment of hydrocele with entailing minimal side effects and low recurrence rate. However, it should not be recommended for the treatment of spermatocele in younger men who still wish to have children, because of the danger of drug epididymitis and resulting infertility. Hydrocele treatment can be performed in younger men who still wish to have children. PMID- 7876765 TI - Endometrial feature and uterine blood flow in abnormal uterine bleeding. AB - We used the transvaginal ultrasound examination in women with abnormal uterine bleeding prior to conventional D&C. It is a simple, non-invasive technic, convenient and accepted by all patients. The endometrial thickness of less than 6 mm is compatible with atrophic endometrium, but of more than 17.7 mm will be malignancy. A cut-off value for endometrial abnormality of 17 mm yielded a sensitivity of 100 per cent, specificity of 96.9 per cent and a positive predictive value of 85.7 per cent respectively (Fisher exac test). When endometrial thickness is more than 17 mm, intratumor flow mean resistance indices can be used to reduce false positive rate. PMID- 7876767 TI - The largest ovarian cyst in Songklanagarind Hospital: a case report. AB - Giant ovarian cysts (more than 12 kilogram) are now rarely seen because of the development in health care systems and education. We report a patient with an ovarian cyst weighing 64 kilogram, marked distended abdomen, tachypnea and dyspnea, pitting edema of both legs and inability to walk. The successful management required multidisciplinary team approach. Slow paracentesis of the cyst was done to relieve 20 litres of fluid before surgery to improve the respiratory function. Subtotal hysterectomy with bilateral salpingo-oophorectomy and partial omentectomy was done with about 4 litres of blood loss during operation. We replaced with 9 units of packed red cells and 25 units of fresh frozen plasma and plasma. Postoperative complications were pneumonia, urinary tract and surgical wound infection which were treated by appropriate antibiotics, dressing and physiotherapy until the patient was able to walk. She was discharged home on postoperative day 33. The pathological report of this cyst was mucinous cystadenoma. Only 4 courses of prophylactic chemotherapy were given because she was lost to follow-up. PMID- 7876766 TI - Clinical study of HIV disease in the lower area of northern Thailand in 1994. AB - Seventy-seven HIV-positive patients admitted to Budhachinaraj Hospital between February and July 1994 were studied. The sex ratio between male and female was 4.1:1 The majority of cases were sexually transmitted. There were 25 cases of symptomatic HIV and 52 cases of full-blown AIDS. The treatment in this study was both medical and psychological. Cryptococcal infection is common in the lower area of northern provinces. Zidovudine has not been widely used. The AIDS patients died of P. carinii pneumonia, cryptococcal meningitis, tuberculous meningitis and toxoplasmic encephalitis respectively. PMID- 7876768 TI - The development of selective attention as reflected by event-related brain potentials. AB - The development of auditory selective attention was assessed using event-related brain potentials (ERPs) and behavioral measures, with children (mean age = 8.1), adolescents (14.4), and young adults (23.8) as subjects. During separate blocks, subjects heard two sequences of pure tones (low- and high-pitched) or consonant vowels (CVs; for example, ba vs da). Subjects were required to attend to one of the two stimuli in order to detect a deviant target embedded within the attended sequence, while ignoring the sequence comprised of the other stimulus (which also contained standard and deviant stimuli). The frequent standards were always 100 ms in duration, whereas the infrequent targets were of longer duration. The effect of selective attention was operationalized by computing the Nd difference waveform (ERP elicited by the unattended standard subtracted from that elicited by the attended standard). There was an increase in early Nd amplitude (measured from about 200 to 400 ms) and a decrease in its latency for both pure tones and CVs from childhood through young adulthood. For the amplitude measure, this effect was much more marked for CVs. Additional analyses indicated that the major effect of age involved reduction of negative-going ERP amplitude elicited by stimuli in the unattended channel, suggesting that with age there is an improvement in the narrowing of the attentional focus, with the major change taking the form of greater facility in rejecting stimuli in the unattended channel. Age-related shifts in scalp distribution of both early and late Nd were seen as consistent with, respectively, age-related changes in the way attention was allocated to the two input channels, and in the way in which the attentional trace was maintained by selective rehearsal. PMID- 7876769 TI - Infants' visual preferences in the presence and absence of auditory stimulation. AB - Two experiments were conducted to explore the hypothesis that altering rate of change of an auditory stimulus will affect infants' fixation of changing visual stimuli. Experiment 1 revealed that average percent time that infants preferred looking at the less stimulating of two meaningless visual displays was highest under conditions of auditory stimulation. Experiment 2 demonstrated a significant inverse linear relation between rate of change of loudness in auditory stimulation and attentiveness to rapidly changing visual stimulation, due largely to decreased looking at the most stimulating display under conditions of auditory stimulation. In addition, the heart rates of a significant number of subjects were found to be accelerated in the presence of auditory stimulation. The results are interpreted as indicating that this type of sensory interaction is mediated, at least in part, by a subject's level of arousal. PMID- 7876770 TI - Semantic and phonological coding in poor and normal readers. AB - Three studies were conducted evaluating semantic and phonological coding deficits as alternative explanations of reading disability. In the first study, poor and normal readers in second and sixth grade were compared on various tests evaluating semantic development as well as on tests evaluating rapid naming and pseudoword decoding as independent measures of phonological coding ability. In a second study, the same subjects were given verbal memory and visual-verbal learning tasks using high and low meaning words as verbal stimuli and Chinese ideographs as visual stimuli. On the semantic tasks, poor readers performed below the level of the normal readers only at the sixth grade level, but, on the rapid naming and pseudoword learning tasks, they performed below the normal readers at the second as well as at the sixth grade level. On both the verbal memory and visual-verbal learning tasks, performance in poor readers approximated that of normal readers when the word stimuli were high in meaning but not when they were low in meaning. These patterns were essentially replicated in a third study that used some of the same semantic and phonological measures used in the first experiment, and verbal memory and visual-verbal learning tasks that employed word lists and visual stimuli (novel alphabetic characters) that more closely approximated those used in learning to read. It was concluded that semantic coding deficits are an unlikely cause of reading difficulties in most poor readers at the beginning stages of reading skills acquisition, but accrue as a consequence of prolonged reading difficulties in older readers. It was also concluded that phonological coding deficits are a probable cause of reading difficulties in most poor readers. PMID- 7876771 TI - Encoding processes and memory organization: a model of the von Restorff effect. AB - The mechanisms underlying the improved recall of isolated events (von Restorff effect) were investigated. Participants studied lists of stimuli containing a physical and a semantic isolate while performing a physical task or a lexical decision task. The physical-task group showed a physical but not a semantic isolation effect (IE) in free recall, whereas the lexical-decision group displayed both types of IEs. The recall of the isolates was independent of that of the other words, and isolates were usually reported separately from other words in the list. Event-related potentials recorded at encoding predicted the recall of both types of isolates. In recognition tests, the IE was obtained only when the encoding context was reinstated. These results are consistent with a model of the IE that stresses the role of the encoding processes immediately following the presentation of distinctive events, and that postulates interactions between these processes and subsequent elaboration of the stimuli. PMID- 7876772 TI - Cognitive representation of motion: evidence for friction and gravity analogues. AB - Five experiments examined whether judgments of the locations of horizontally moving targets were influenced by implied friction between the targets and larger stationary surfaces. When targets crashed through a barrier, forward displacement decreased. When targets slid along the upper or lower edge of a single surface, forward displacement decreased. When targets slid along the upper or lower edge of a single surface, forward displacement decreased; when targets slid between the upper and lower edges of different surfaces, forward displacement decreased further. Targets not in contact with a surface exhibited larger forward displacement with greater target velocities, but contact with a surface attenuated or reversed this pattern. When targets slid along the upper edge of a surface, downward displacement increased; when targets slid along the lower edge of a surface, downward displacement reversed. Downward displacements were larger for larger targets, especially after contact with a surface. The data suggest that target representations contain analogues to friction and gravity that influence remembered position. PMID- 7876774 TI - Determinants of parafoveal preview benefit in high and low working memory capacity readers: implications for eye movement control. AB - The experiment in this article extended studies by A. W. Inhoff and K. Rayner (1986) and J. M. Henderson and F. Ferreira (1990) to determine how the printed frequency of two adjacent words influenced the benefit of having parafoveal preview of the 2nd word. High- and low-span participants (assessed by M. Daneman and P. A. Carpenter's, 1980, Reading Span Test) were tested to determine whether working memory capacity influenced parafoveal preview benefit. Parafoveal preview benefit was determined by an interaction of both words' frequencies in first fixation and by the 2nd word's frequency in gaze duration. However, readers were generally fixated closer to the beginning of the 2nd word when the 1st word was low frequency. When the viewing distance confound was minimized, the prior word's frequency did affect parafoveal preview benefit. Parafoveal preview benefit did not vary between reading groups. Group distributions of fixation duration provided no evidence for J. M. Henderson and F. Ferreira's fixation cutoff model. PMID- 7876773 TI - The cocktail party phenomenon revisited: how frequent are attention shifts to one's name in an irrelevant auditory channel? AB - N. Moray's (1959) well-known study of the "cocktail party phenomenon" suggested that participants sometimes notice their name embedded in an ignored auditory channel. However, the empirical finding was preliminary in nature and never has been directly replicated. This was done with improved methodological controls, and the relationship between on-line attention shifts to one's name and subsequent recollection of the name in a sample of 34 undergraduates was examined. Similar to N. Moray, only 34.6% of the participants recalled hearing their name in the channel to be ignored. Only those participants showed on-line evidence of attention shifts, and those shifts occurred only for the two items following the name. The results suggest that participants who detected their name monitored the irrelevant channel for a short time afterward. PMID- 7876775 TI - Grouping in primary memory: the case of the compound suffix. AB - Appending a nominally irrelevant item, or "suffix," to the end of a short list of items impairs recall of the list. Appending a second such item, however, does not increase the impairment. The research reported here shows that the impairment can in fact be increased if the suffix items are physically dissimilar. Thus, Experiments 1-4 show that memory for a sequence of digits is impaired more by the addition of two zeros uttered in different voices than by either a single zero or two zeros uttered in the same voice. Experiment 5 shows a similar pattern of results in the visual modality, with physical similarity defined by typefont. The findings are contrary to at least two theories of the suffix effect but can be accounted for by assuming that physically similar items tend to form a cohesive group. PMID- 7876776 TI - Family practice procedures. PMID- 7876777 TI - Night of the iguana. PMID- 7876778 TI - JFP Journal Club: growing and going online. PMID- 7876779 TI - A comparison of manual and ultrasound measurements of fundal height. AB - BACKGROUND: Uterine fundal height has long been used to assess fetal growth. The common prediction rule states that the distance in centimeters between the pubic symphysis and the top of the fundus equals the gestational age in weeks. The correlation holds best between weeks 18 and 32. This study compares manual and ultrasound measurements of fundal height. METHODS: We compared palpated and ultrasound symphysis-fundal height. We then compared both measurements with gestational age as determined by usual ultrasound measurements. Patients were statistically separated by weight into two groups: normal and obese. We hypothesized that manual measurements of fundal height would be affected by obesity and race. RESULTS: Ultrasound fundal height and manual fundal height were equivalent (P < or = .01, R2 = .92). Regression analysis in normal weight and obese patients showed that both methods have the same predictive power in determining fetal age. CONCLUSION: Manual measurements are still a reliable and inexpensive means of evaluating the course of pregnancy. Ultrasound is needed when there is a size-vs-date discrepancy. Ultrasound is also useful for teaching the measurement of fundal height. PMID- 7876780 TI - Where do panic attack sufferers seek care? AB - BACKGROUND: Although 40% of people with panic attacks never seek care for their attacks, those who do may use medical settings or mental health settings, or both. The purpose of this study was to examine where people seek care for their panic attacks within and outside the health care system, and to determine what variables predict the choice of a given site. METHODS: The Panic Attack Care Seeking Threshold (PACT) study is a community-based survey of 97 subjects meeting the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) criteria for panic attacks. A structured interview was used to collect information about panic attacks, family characteristics, psychiatric comorbidity, health care access and utilization, illness attitudes and behaviors, quality of life, and symptom perceptions. RESULTS: Forty-nine percent of the subjects seeking care for panic attacks presented to medical settings, whereas 26% of subjects used mental health settings. The family physician's office was the most frequent site of presentation (35%), followed by a hospital emergency department (32%). Only 13% of subjects sought care from a site outside the health care system. Variables predicting presentation to specific health care sites varied. Subject demographics, panic characteristics, and symptom perceptions were generally significant factors in care-seeking. Illness behaviors, readiness for sick role, health locus of control, and family measures failed to predict the seeking of care specific to any particular site. CONCLUSIONS: When subjects with panic attacks seek care, they most commonly present to a general or family physician's office or a hospital emergency department. PMID- 7876781 TI - The effect of epidural anesthesia on the length of labor. AB - BACKGROUND: Epidural anesthesia, although effective, has been associated with changing the course of labor. Previous studies have been criticized for not pinpointing the factors determining the use of epidural anesthesia. The purpose of this study was to determine the effect of epidural anesthesia use on the course of labor. METHODS: A retrospective chart review of 224 women who gave birth from July 1, 1993, to June 30, 1994, was completed in a small-town family practice. The time frame included 6 months before and after the initiation of Tenncare, a state-funded health insurance plan designed to serve the uninsured and those previously served by Medicaid in Tennessee. RESULTS: The rate of epidural anesthesia use in this study population fell sharply after January 1, 1994, the start date for Tenncare. Epidural anesthesia by women in this study was found to increase the average length of the second stage of labor by 38 minutes for primiparas and 23 minutes for multiparas. CONCLUSIONS: The average length of the second stage of labor is significantly longer for women who receive epidural anesthesia. The rate of epidural anesthesia use in this study population was strongly influenced by a change in health-care financing. PMID- 7876782 TI - The role of physicians' personal knowledge of the patient in clinical practice. AB - BACKGROUND: Primary care physicians' personal knowledge of their established patients has not been investigated systematically, and its role in clinical practice has not been characterized empirically. METHODS: A qualitative study used an iterative, grounded theory method for thematic analysis of transcribed, semistructured long interviews. Subjects were family physicians in stable employment and in continuous clinical practice for at least 2 years at a staff model health maintenance organization. RESULTS: Personal knowledge of the patient clearly influenced the use of time in the examination room, the recognition of changes in baseline status, and the ability to verbalize medical information in terms that have unique meaning for particular patients. Personal knowledge fostered a sense of predictability in personal interactions; facilitated the creation of trust; served as an organizing scheme for data collection, recall, and interpretation; counterbalanced impersonal professional principles such as compulsiveness, duty, and responsibility; shaped ability to communicate effectively about issues related to quality of life and functional status; influenced choices of consultants; but also had the potential to interfere with diagnosis or with patient presentation of new information. CONCLUSIONS: Personal knowledge of patients was an important influence on physicians' daily clinical practice in this setting. PMID- 7876783 TI - Computer-prompted diagnostic codes. AB - BACKGROUND: The purpose of this study was to develop and evaluate a computer system that would translate patient diagnoses noted by a physician into appropriate International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes and maintain a patient-specific up-to-date problem list. METHODS: The intervention consisted of a computerized list (dictionary) of diagnoses, including practice-specific synonyms and abbreviations, linked to their corresponding ICD-9-CM codes. To record the diagnoses for the office visit before the intervention, physicians used International Classification of Health Problems in Primary Care (ICHPPC-2) codes. After the intervention, physicians used their own words or checked previously identified diagnoses on the computer generated problem list. The computer then identified the correct ICD-9-CM code. Accuracy of coding was compared before and after the new computerized system was implemented. RESULTS: Visits in which all diagnoses matched increased from 58% to 76% (P < .001) with use of the computer system. Visits in which no computer diagnoses matched the chart decreased from 22% to 8% (P < .001). Errors of omission declined from 38% to 18% (P < .001). Errors of commission decreased from 19% to 11% (P = .006). Overall accuracy increased from 62% to 82% (P < .001). CONCLUSIONS: Outpatient medical diagnosis coding can be simplified and accuracy improved by using a computerized dictionary of practice-specific diagnoses and synonyms linked to appropriate ICD-9-CM codes. Such a system provides a computer generated problem list that accurately reflects the chart and assists with prompted coding on subsequent visits. PMID- 7876784 TI - Breast-feeding education and practice in family medicine. AB - BACKGROUND: Physician support has been shown to increase breast-feeding rates, but anecdotal reports suggest that physicians are ill prepared for their role in breast-feeding promotion. Inadequate breast-feeding education during residency training may be a contributing factor. METHODS: A self-administered questionnaire mailed to 1099 family medicine residents and 665 recently board-certified family physicians assessed knowledge, attitudes, education, and activity related to breast-feeding promotion. Response rates were 71% for residents and 58% for physicians. RESULTS: Although residents and physicians were strongly convinced that family physicians should be involved in breast-feeding promotion, both groups demonstrated significant deficits in knowledge about breast-feeding benefits and clinical management strategies. Common errors included inappropriate recommendations for breast-feeding termination or formula supplementation, a proven cause of breast-feeding failure. Personal breast-feeding experience was the only factor consistently associated with more frequent breast-feeding promotion activity among residents and increased self-confidence for both groups. Respondents reported only limited opportunities for developing breast-feeding counseling skills during residency training. CONCLUSIONS: Improved breast-feeding education is needed for family medicine residents and physicians. Residency training and continuing education programs should emphasize the benefits of breast-feeding, clinical management strategies, and development of practical counseling skills. PMID- 7876785 TI - Attention-deficit/hyperactivity disorder: assessment, diagnosis, and management. AB - Children and adolescents with attention-deficit/hyperactivity disorder (AD/HD) frequently present to family physicians for evaluation and treatment. Recently, revised criteria for diagnosis of this condition were presented in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders. Attention deficit/hyperactivity disorder is often difficult to differentiate from other disruptive behavior syndromes, such as oppositional defiant disorder and conduct disorder. Using a systematic process of differential diagnosis and integrating the mental status examination with history and teacher and parent reports, the family physician will be able to diagnose AD/HD with greater accuracy. Treatment with stimulant medication and behavioral strategies yields positive outcomes with these children. PMID- 7876786 TI - The five generations of American medical revolutions. AB - Current medical authors frequently use the term "revolution," yet American medicine is resisting change rather than embracing it. The last completed American medical revolutionary movement was the specialist-technologist movement of the late 19th and early 20th centuries. This paper describes a five generational model of revolution. First-generation persons foment revolution; second-generation persons shape it into workable form and precipitate conflict; third-generation persons join the fight only when it appears to be all but won; fourth-generation persons enjoy the fruits of revolution; and fifth-generation persons, having risen to domination in the mature system, resist all attempts at reform by the next round of revolutionaries. In political revolutions, severe reactionary activity by the ruling party is often an indicator of an imminent overthrow by revolution. In scientific revolutions, the opposition of an established (specialist-technologist) paradigm to an emerging alternative (generalist) paradigm increases in intensity as the old order declines in strength; the opposition becomes most fierce just before the collapse of the old order. American specialist-technologist medicine, declining into its senescent fifth generation, will resist all but incremental change whenever possible, and accept major change only by force. PMID- 7876787 TI - 'Vampire syndrome': serum protein and lipid abnormalities related to frequent sale of plasma. AB - The sale of plasma for profit has become a common occurrence. In the United States, a healthy individual can donate as frequently as six times per month and up to 60 L of plasma per year. Although plasma donors are generally healthy, intervening conditions can increase the catabolism or decrease the synthesis of certain serum constituents and thereby produce a confusing clinical picture. In 1 month, we encountered two patients who presented with hypoalbuminemia and hypocholesterolemia for which there was no obvious cause except a history of frequent plasma sales. PMID- 7876788 TI - Breast-feeding education among family physicians. PMID- 7876789 TI - Efficacy of influenza vaccine in the elderly. PMID- 7876790 TI - Vitreous humor cocaine and metabolite concentrations: do postmortem specimens reflect blood levels at the time of death? AB - The interpretation of postmortem cocaine concentrations is made in an attempt to estimate drug concentrations present at the time of death and thus infer not only drug presence but drug toxicity. Previous data suggest that changes in postmortem blood cocaine concentrations over time are not predictable and interpretation of cocaine levels should be done with caution. However, these data come from autopsy case series where vital information, such as blood cocaine concentration at the time of death, dose and time since last use, and postmortem interval is often not known. The purpose of this study was to characterize postmortem changes in cocaine and metabolite concentrations relative to premortem concentrations over time at two anatomic sites: peripheral blood and vitreous humor, in a controlled, large animal model. Juvenile swine were given cocaine HCl 10 mg/kg as an IV bolus which resulted in seizures and wide complex tachycardia. Five minutes after cocaine administration, animals were euthanized. At time of death and eight hours postmortem, femoral venous blood and vitreous humor (VH) samples were obtained for quantitation of cocaine, benzoyl ecgonine (BE), and ecgonine methyl ester (EME) by GC/MS. There were no significant increases over time in mean femoral vein concentrations of cocaine or BE. However, a large interanimal variability in direction and magnitude of concentration changes was seen. Mean EME concentrations at the femoral site increased significantly over 8 hours (P < 0.03). Mean VH cocaine concentrations at time of death were significantly lower than corresponding blood concentrations (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876791 TI - Evaluation of the Abuscreen ONLINE assay for amphetamines on the Hitachi 737: comparison with EMIT and GC/MS methods. AB - The performance of the ONLINE Assay for Amphetamines on the Hitachi 737 was compared to the Syva Emit d.a.u. Assay and GC/MS. Randomly screened (n = 2964) patient urine samples were assayed using ONLINE and Emit d.a.u. assays concurrently, using d-amphetamine, 1000 ng/mL and d-methamphetamine, 1000 ng/mL as the screening cutoff for ONLINE and Emit d.a.u. assays, respectively. All presumptive positives were confirmed by GC/MS. The specificity was 99% (2937/2964) for ONLINE and 97% (2873/2964) for Emit. Agreement with GC/MS was 80% (110/137) for ONLINE and 55% (110/201) for Emit. PMID- 7876792 TI - Evaluation of a rapid assay system, HIV 1/HIV 2 Testpack, Abbott, to detect human immunodeficiency virus antibodies in postmortem blood. AB - For evaluating the HIV 1/HIV 2 Testpack (Abbott, Chicago, IL) to detect antibodies to human immunodeficiency virus (HIV) in whole postmortem blood 456 samples were collected prior forensic autopsies. All samples were tested using the enzyme-linked immunoassay (ELISA) and the Testpack; positively reactive samples and samples with equivocal results were confirmed by Western blot. Of the 456 samples 21 (4.6 per cent) proved to be reactive in both systems (confirmed by Western blot). In 17 cases (3.7 percent) interpretation of the result was difficult, but no serious misinterpretations occurred. It is concluded that the HIV-Testpack provides accurate results in testing whole postmortem blood for HIV antibodies. PMID- 7876793 TI - An ELISA procedure for the detection of soluble ABH blood group substance in semen, saliva, and vaginal samples. AB - Enzyme linked immunosorbent assay (ELISA) was used for the detection of ABH blood group substances in body fluids. The original procedure was modified to provide maximum sensitivity and reliability. The modified ELISA method proved to be more sensitive and required much less sample than previously described techniques. PMID- 7876794 TI - Identification of an unknown corpse by means of computed tomography (CT) of the lumbar spine. AB - For the first time, a case is described in which an unknown corpse is identified by the comparison of antemortem and postmortem computed tomographic (CT) images. A posterolateral disc herniation at L5-S1 on the right side, Schmorl's nodes and a lucency in the ilium were found in identical locations in each case. Additionally there were characteristic morphological similarities in the vertebral bodies, spinous processes, transverse processes and neural arches. In CT identification, as in conventional radiographic identification, one must try to reproduce comparable scanning conditions and images because apparent differences in the roentgenological morphology can occur as a result of different gantry angles or slice thicknesses. PMID- 7876795 TI - Fatal moclobemide overdose or death caused by serotonin syndrome? AB - A 41-year-old man was found dead in a hotel room. He was previously diagnosed with depression. Multiple containers of medication and paraphenalia were found at the scene. Autopsy findings included fully developed rigor mortis and pulmonary edema with hemorrhage. Toxicologic analysis of different body fluids was performed and the following drugs were identified in the blood (mg/L): moclobemide (59.76), clomipramine (1.69), tramadol (10.89), diazepam (2.08), nordiazepam (0.82) and caffeine (9.64). A fatal serotonin syndrome was presumably developed as a result of moclobemide-clomipramine interaction as has been recently reported. Tramadol could have a synergistic effect on that syndrome. The forensic pathologists ruled that the cause of death was multiple drug intoxication resulting in serotonin syndrome and that the manner of death was suicide. However, an accidental death from drug abuse could be an alternative diagnosis. PMID- 7876796 TI - Fatal intracranial hemorrhage following pediatric oral surgical procedure. AB - Deaths during dental and oral surgical procedures may lead to litigation alleging malpractice. For this reason, and because of their sudden and unexpected nature, they often come to the attention of forensic pathologists. We review the clinical and anatomic findings of a 3-year-old boy who expired following an oral surgical procedure in the temporomandibular region. During the operation, perforation of the base of the skull occurred causing laceration of a branch of the middle meningeal artery and fatal subdural and epidural bleeding. PMID- 7876797 TI - Homicide facilitated by inhalation of chloroform. AB - Three related homicides in which each decedent had significant concentrations of chloroform in blood, fat, brain and/or liver are described. The tissue concentrations of chloroform in one of three decedents were within reported lethal ranges. The concentrations in the remaining two decedents were less than lethal but were well above blood levels in nonoccupationally exposed, healthy subjects. The cause of death in one decedent with sublethal chloroform concentrations was suffocation; the cause of death in the other decedent could not be determined with certainty. The manner of death in each case was homicide. Through a review of the literature the authors discuss the history of chloroform as an inhalation anesthetic and the history of chloroform as an agent of abuse, suicide, assault, and homicide. Blood and/or tissue concentrations of chloroform in nonoccupationally exposed, healthy subjects and victims of suicide or homicide from previous reports are compared and contrasted with the amounts in blood and/or tissue in the three subjects described in this study. The authors conclude that, in addition to a direct lethal effect, chloroform may be used to incapacitate a victim of assault who then dies by another cause. PMID- 7876798 TI - A bloodstain pattern interpretation in a homicide case involving an apparent "stomping". AB - A New York City homicide case was investigated at the request of the District Attorney's office. The deceased had been violently beaten about the face, neck, and chest area. The bludgeoning left the victim unrecognizable, and produced blood-spatter patterns at the scene that attained heights over nine feet. The suspect claimed that he reacted in self-defense to the victim's attack with a table leg at which point he "knocked him down" and possibly "kicked him a few times." Our investigation was intended to determine whether the bloodspatter patterns observed at the crime scene were consistent with the statements made by the defendant. Conclusions were drawn from an analysis of the crime scene, autopsy photos and report, physical evidence submitted to the laboratory, and reconstruction experimentation performed at the Office of Chief Medical Examiner (OCME). The spatter patterns observed at the scene were found to be consistent with those that would be produced from a "stomping" incident. PMID- 7876799 TI - Comprehensive forensic analyses of debris from the fatal explosion of a "cold fusion" electrochemical cell. AB - Selected components of explosion debris from the SRI International incident of January 2, 1992 were subjected to forensic analyses to elucidate potential causes of, or contributing factors to, the explosion. Interrogation of the debris encompassed nuclear, chemical, physical, and materials investigations. Nuclear studies for the determination of tritium and neutron-activation products in stainless steel and brass were conducted. No evidence for signature species indicative of orthodox nuclear events was detected. The inorganic and particulate analyses were likewise negative with respect to residues of unexpected chemical species. Such target compounds included conventional explosives, accelerants, propellants, or any exceptional industrial chemicals. Materials characterization identified the type of stainless steel used in the manufacture of the electrolytic cell as one relatively high in Mo concentration, probably type 316. Metallurgical analyses of the cell vessel wall and its detached base provided no evidence of corrosion or hydrogen embrittlement, leaving only ductile failure of the weld as contributing to the incident. The weld was found to have missed the center-line of the step joint, and the average penetration of the weld was measured to be 54%. The GC-MS analyses of trace organic components in the explosion debris provided a most interesting result. Although no evidence of organic explosives, oxidizers, or other unusual compounds was detected, the presence of an organic oil in the interior of the electrochemical cell was established. It is likely that the source of this oil was lubricating fluid from machining the metal cell components.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876800 TI - D1S80 population data in African Americans, Caucasians, southeastern Hispanics, southwestern Hispanics, and Orientals. AB - Allele frequencies for the locus D1S80 were determined in African American, Caucasian, Southeastern Hispanic, Southwestern Hispanic, and Oriental sample populations using the polymerase chain reaction and subsequent electrophoresis and silver staining of the amplified products. Due to the presence of anodal and cathodal electrophoretic variants (in reference to the steps in an allelic ladder), allele frequencies were established using a classification protocol based on the steps in the allelic ladder. All sample populations met Hardy Weinberg expectations for D1S80. In addition, there was no evidence for association of alleles between the loci D1S80 and D1S7. The product of allele frequencies from the data from the sample populations in this study can be used in forensic analyses and paternity tests to estimate the frequency of a D1S80 DNA genotype. PMID- 7876801 TI - Validation and population studies of the loci LDLR, GYPA, HBGG, D7S8, and Gc (PM loci), and HLA-DQ alpha using a multiplex amplification and typing procedure. AB - Studies were performed to evaluate the forensic applicability of multiplex amplification of the loci low density lipoprotein receptor, glycophorin A, hemoglobin G gammaglobin, D7S8, and group-specific component (PM loci) and simultaneous typing of these loci using a reverse dot blot approach where allele specific oligonucleotide probes are immobilized on a nylon membrane strip. These results were obtained by using the AmpliType PM PCR Amplification and Typing Kit. The experiments included: mixed body fluid studies; chemical contaminant effects on the DNA in body fluid samples; the effect of typing DNA from body fluid samples deposited on various substrates; the effect of microorganism contamination on typing DNA derived from blood and semen; the effect of sunlight and storage conditions on DNA typing; determination of the sensitivity of detection of the PM test kit; determination of cross-reactivity of DNA from species other than human; typing DNA derived from various tissues from an individual; and an evaluation of the hybridization temperature of the assay. The data demonstrate that DNA exposed to a variety of environmental insults yields reliable PM typing results. Allele and genotype frequencies for six loci (PM loci and HLA-DQ alpha) were determined in African Americans. Caucasians, southeastern Hispanics, and southwestern Hispanics. All loci meet Hardy-Weinberg expectations and there is little evidence for association of alleles between the loci. The frequency data can be used in forensic analyses and paternity tests to estimate the frequency of a multiple locus DNA profile in various general United States populations. PMID- 7876802 TI - Medical examiner/death investigator training requirements in state medical examiner systems. AB - Comprehensive and properly performed investigation of suspicious, unusual, unnatural, and various natural deaths is necessary to maintain the health, safety, and well-being of society as a whole. Adequate investigation requires the combined efforts and cooperation of law-enforcement and other public-service agencies, medical professionals, and those within the forensic community. As such, the "death investigator" plays a crucial role in the investigation process. These front-line investigators, whether they be coroners, medical examiners, physicians, other medical professionals, or lay-people, are required to make important decisions which have far-reaching consequences on how death investigation cases proceed. Death investigation practices vary greatly among medico-legal jurisdictions. A recent publication has categorized state death investigation systems by type of system. In an attempt to better delineate death investigation practices with specific regard to investigators' training and continuing education requirements, we surveyed the 20 systems categorized as state medical examiner systems and the five states with combined state medical examiner and county coroner/medical examiner systems. We present our findings and make recommendations which address the attributes and deficiencies of current death investigation practices. PMID- 7876803 TI - Estimation of stature from the length of the cervical, thoracic, and lumbar segments of the spine in American whites and blacks. AB - In order to estimate stature from the length of cervical, thoracic, lumbar, thoraco-lumbar (T-L) and cervico-thoraco-lumbar (C-T-L) segments of the spine, measurements were made on white and black Americans, both male and female, autopsied during 1977-1993. Sample sizes were as follows: white males = 167; white females = 58; black males = 43; black females = 31. Separate measurements were made of the vertebral segments along the anterior surface of the spine. Regression formulae were calculated for each segment in each of the four groups. Standard errors of estimate ranged from 2.60 to 7.11 cm. Comparison was made with previous work published for Japanese. The Japanese formulae could not predict stature of the American populations using our data. The method is useful for estimating the stature of severely burned or mutilated bodies. PMID- 7876805 TI - The current status of research in forensic psychophysiology and its application in the psychophysiological detection of deception. AB - Since 1986 there have been unparalleled advances in the psychophysiological detection of deception (PDD) processes and procedures. This paper traces the emergence of a new emphasis in PDD research; the development of forensic psychophysiology as an academic discipline; provides an overview of computerized polygraphs now in use for collecting physiological data; introduces new sensors and transducers currently under study; and describes a new instrument now under development. PMID- 7876804 TI - Analysis of heroin drug seizures by Micellar Electrokinetic Capillary Chromatography (MECC). AB - A rapid procedure using Micellar Electrokinetic Capillary Chromatography (MECC) is presented for the quantitation of illicit heroin samples. This analytical system resolves heroin from accompanying impurities and adulterants enabling accurate quantitation via the use of an internal standard. An aqueous run buffer consisting of 40 mmol sodium dodecyl sulfate, 8.5 mmol sodium phosphate, 8.5 mmol sodium borate and 15% acetonitrile is used with a 27 cm x 50 microns fused silica capillary column. Linearity, accuracy and reproducibility studies of heroin using this method are established. Comparisons to a commonly used gas chromatographic method show excellent correlation. Due to its high resolution and speed, this MECC system also serves as a screening procedure to detect impurities and adulterants present in heroin samples. Relative migration times of various opiates and adulterants are reported. With minor exceptions, complete separation of numerous compounds is achieved within five minutes, including compounds that are difficult to analyze by gas chromatography such as morphine, O6 acetylmorphine, aspirin and salicylic acid. PMID- 7876806 TI - Mentally abnormal killers in the UK health care system: issues facing the multidisciplinary team. AB - In the UK, mentally ill offenders can be assessed and given treatment and rehabilitation in a secure health care setting rather than in a correctional facility. Beds in such health care facilities are limited and evidence suggests that only the most serious offenders, such as those who have committed a homicide, are given priority. This paper examines the role of the Regional Secure Unit, a National Health Service provision, in the assessment and treatment of these offenders. A number of issues facing the multidisciplinary team are raised. A case study is presented to illustrate some of these points. PMID- 7876807 TI - Determinations of dangerousness in forensic patients: an archival study. AB - The involvement of mental health professionals in determinations of dangerousness is both common and controversial. Among the various contexts for these evaluations, the release of potentially violent forensic patients from maximum security facilities evokes justified concern from involved experts and apprehension to outrage from the immediate community. We sought to examine how conclusions are reached on dangerousness at two sequential stages: clinical recommendations and Manifest Dangerousness Hearings decisions. In an archival study of 245 patients, we found that lack of progress in the institution and physical assaultiveness were the strongest correlates with dangerousness. In contrast, experts and review boards appeared to be relatively less influenced by diagnosis, types of treatment, and sociodemographic variables. PMID- 7876808 TI - Extraction of psychotropic drugs from human scalp hair. AB - A comparison of techniques for the extraction of antidepressant and antipsychotic drugs in human scalp hair is described. Human scalp hair was obtained from cadavers known to be taking psychotropic drugs prior to their death. Following a washing step, hair was either solubilized in sodium hydroxide, or treated with dilute hydrochloric acid, methanol or subtilisin. Digests were treated with a solvent and the extracted drugs quantified by high performance liquid chromatography. The alkaline digestion procedure was found to be significantly more effective (P < 0.01) in recovering a range of antidepressant and antipsychotic drugs from hair than either the acidic, methanolic or enzymatic treatments. PMID- 7876809 TI - Detection of antidepressant and antipsychotic drugs in postmortem human scalp hair. AB - The presence of therapeutic drugs in postmortem human scalp hair was investigated. Hair samples from 21 cadavers known to have taken antidepressant and antipsychotic drugs were solubilized in 1 M sodium hydroxide. Drugs were extracted using solvent extraction procedures and analyzed by gas chromatography mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC). Antidepressant drugs detected were amitriptyline, dothiepin, doxepin, imipramine, trimipramine, and mianserin. Antipsychotic drugs detected were haloperidol, chlorpromazine and thioridazine. Concentrations of these drugs and their metabolites ranged from 1.3 to 242 ng/mg hair. Segmental analysis demonstrated that the drug concentrations detected were either consistent with the known dosing regime of the deceased, or were able to provide an indication of drug use within the last few months prior to death. This study reinforces the potential of hair as a useful tissue in forensic investigations, in establishing a history of past exposures to therapeutic drugs. PMID- 7876810 TI - An evaluation of the reliability of Widmark calculations based on breath alcohol measurements. AB - This study evaluated the reliability of Widmark calculations, based on breath ethanol reading (BrACs), for estimating the amount of alcohol consumed. A standard ethanol dose (males 0.51 g/kg; females 0.43 g/kg) was given to 115 college seniors, and BrACs were measured for two hours. Calculations of ethanol dose were performed using BrACs taken at 60, 75, 105, and 125 minutes after drinking. Mean calculated ethanol doses were lower than actual doses at each time point (P < 0.001). Mean underestimates were 13, 12, 15, and 14 mL of 100 proof vodka at 60, 70, 105, and 125 min after drinking. Calculated doses overestimated actual doses in 11, 10, 3, and 3 subjects at 60, 75, 105, and 125 min after drinking. The maximum overestimates were 13, 11, 6, and 8 mL of vodka at 60, 75, 105, and 125 min after drinking. At the 95% confidence level, the calculated dose at 105 and 125 min did not overestimate the true dose, but could underestimate it by as much as 30 mL vodka. PMID- 7876811 TI - Benzoylecgonine and ecgonine methyl ester concentrations in urine specimens. AB - The two major urinary metabolites of cocaine are benzoylecgonine (BE) and ecgonine methyl ester (EME). The major advantage of BE screening is that many commercial immunoassays are designed to detect BE. On the other hand, EME is more amenable to gas chromatographic screening. To ascertain the merits of screening BE versus EME for identifying cocaine use, 380 consecutive urine specimens presented to the Office of the Chief Medical Examiner-State of Maryland were tested for BE by EMIT (cutoff 0.3 mg/L) and for EME by gas chromatography nitrogen-phosphorus detection (cutoff 0.05 mg/L). Each presumptive positive was confirmed by gas chromatography-mass spectrometry. One hundred four specimens tested positive for BE or EME. Ninety three specimens were positive for both BE and EME, seven were positive for BE (cutoff 0.05 mg/L) only and four were positive for EME only. BE concentrations ranged from 0.08-386 mg/L while EME concentrations ranged from 0.06-72 mg/L. The BE concentration was greater than or equal to the EME concentration in 73% of the cases. Using BE as a sole screen, 96% of the cases of cocaine use were identified while EME screening identified 93% of the cases. PMID- 7876812 TI - Regulatory intrusion into patient pain relief. PMID- 7876813 TI - The nose knows. PMID- 7876814 TI - Latex particle agglutination tests on the cerebrospinal fluid. A reappraisal. AB - Rapid diagnostic tests are often used to identify microbial etiology of infection early. Latex particle agglutination (LPA) tests on the cerebrospinal fluid (CSF) are frequently used for purpose of rapid diagnosis. We evaluated their usefulness in management of patients with suspected meningitis. We also evaluated the cost effectiveness of LPAs during an 11-month period; 1,540 CSF specimens were tested for H. influenzae type b, Group B streptococcal (GBS), N. meningitidis and S. pneumoniae using LPAs. Only 27 were positive. LPAs were useful in management of only the neonates with GBS infection. On the whole, LPAs were very expensive and not cost-effective. PMID- 7876815 TI - Outcome assessment in depressed hospitalized patient. AB - Psychiatric symptoms as well as work, social, and physical functioning were compared in two groups of psychiatric patients (36 depressed only and 34 depressed in conjunction with an eating disorder) and 77 controls. In both groups, Global Assessment of Functioning (GAF) scores significantly improved from hospital admission to discharge and remained improved at 1.5 years postdischarge. As outpatients, the GAF, Zung Depression, and anxiety scores of both groups were significantly lower than for controls. Ratings of social functioning for depressed only outpatients did not differ from controls on five out of six measures. Predictors of posthospital improvement included high satisfaction with hospital treatment, high GAF scores on admission to hospital, perceived effectiveness of outpatient therapy, younger age, and an historical absence of sexual abuse or prior psychiatric hospitalization. PMID- 7876817 TI - A good doctor. PMID- 7876816 TI - Caveat employer. Personal service contracts for physicians. PMID- 7876818 TI - Coup d'etat ... American style. PMID- 7876819 TI - Responses to Kirkpatrick et al article. PMID- 7876820 TI - Responses to Kirkpatrick et al article. PMID- 7876821 TI - Responses to Kirkpatrick et al article. PMID- 7876822 TI - Responses to Kirkpatrick et al article. PMID- 7876823 TI - Responses to Kirkpatrick et al article. PMID- 7876824 TI - Properties of single cardiac Na channels at 35 degrees C. AB - Single Na channel currents were recorded in cell-attached patches of mouse ventricular myocytes with an improved patch clamp technique. Using patch pipettes with a pore diameter in the range of 200 nm, seals with a resistance of up to 4 T omega were obtained. Under those conditions, total noise could be reduced to levels as low as 0.590 pA rms at 20 kHz band width. At this band width, properties of single-channel Na currents were studied at 35 degrees C. Six out of a total of 23 patches with teraohm seals contained channel activity and five of these patches contained one and only one active channel. Amplitude histograms excluding transition points showed heterogenous distributions of levels. In one patch, part of the openings was approximately Gaussian distributed at different potentials yielding a slope conductance of 27 pS. The respective peak open probability at -10 mV was 0.26. The mean open time was determined at voltages between -60 and -10 mV by evaluation of the distribution of the event-related gaps in the center of the baseline noise to be approximately 40 microseconds at 60 mV and 50-74 microseconds between -50 and -10 mV. It is concluded that single cardiac Na channels open at 35 degrees C frequently with multiple levels and with open times in the range of several tens of microseconds. PMID- 7876826 TI - Origins of open-channel noise in the large potassium channel of sarcoplasmic reticulum. AB - Open-channel noise was studied in the large potassium channel of the sarcoplasmic reticulum (SR). Inside-out patches were excised directly from the SR of split skeletal muscle fibers of lobster, with lobster relaxing ringer (LRR) in bath and pipette. The power spectrum of open-channel noise is very low and approximately flat in the 100 Hz-10 kHz frequency range. At 20 degrees C, with an applied voltage of 50 mV, the mean single-channel current (i) is 9 pA (mean single channel conductance = 180 pS) and the mean power spectral density 1.1 x 10(-29) A2/Hz. The latter increases nonlinearly with (i), showing a progressively steeper dependence as (i) increases. At 20 mV, the mean power spectral density is almost independent of (i) and approximately 1.4 times that of the Johnson noise calculated for the equivalent ideal resistor with zero net current; at 70 mV it increases approximately in proportion to (i)2. The mean power spectral density has a weak temperature dependence, very similar to that of (i), and both are well described by a Q10 of 1.3 throughout the range 3-40 degrees C. Discrete ion transport events are thought to account for a significant fraction of the measured open-channel noise, probably approximately 30-50% at 50 mV. Brief interruptions of the single-channel current, due either to blockage of the open channel by an extrinsic aqueous species, or to intrinsic conformational changes in the channel molecule itself, were a possible additional source of open-channel noise. Experiments in modified bathing solutions indicate, however, that open channel noise is not affected by any of the identified aqueous species present in LRR. In particular, magnesium ions, the species thought most likely to cause brief blockages, and calcium and hydrogen ions, have no detectable effect. This channel's openings exhibit many brief closings and substrates, due to intrinsic gating of the channel. Unresolved brief full closings are calculated to make a negligible contribution (< 1%) to the measured power spectral density. The only significant source of noise due to band width-limited missed events is brief, frequent 80% substrates (mean duration 20 microseconds, mean frequency 1,000 s-1) which account for a small part of the measured power spectral density (approximately 14%, at 50 mV, 20 degrees C). We conclude that a large fraction of the measured open-channel noise results from intrinsic conductance fluctuations, with a corner frequency higher than the resolution of our recordings, in the range 10(4)-10(7) Hz.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7876825 TI - Inositol (1,4,5)-trisphosphate (InsP3)-gated Ca channels from cerebellum: conduction properties for divalent cations and regulation by intraluminal calcium. AB - The conduction properties of inositol (1,4,5)-trisphosphate (InsP3)-gated calcium (Ca) channels (InsP3R) from canine cerebellum for divalent cations and the regulation of the channels by intraluminal Ca were studied using channels reconstituted into planar lipid bilayers. Analysis of single-channel recordings performed with different divalent cations present at 55 mM on the trans (intraluminal) side of the membrane revealed that the current amplitude at 0 mV and the single-channel slope conductance fell in the sequence: Ba (2.2 pA, 85 pS) > Sr (2.0 pA, 77 pS) > Ca (1.4 pA, 53 pS) > Mg (1.1 pA, 42 pS). The mean open time of the InsP3R recorded with Ca (2.9 ms) was significantly shorter than with other divalent cations (approximately 5.5 ms). The "anomalous mole fraction effect" was not observed in mixtures of divalent cations (Mg and Ba), suggesting that these channels are single-ion pores. Measurements of InsP3R activity at different intraluminal Ca levels demonstrated that Ca in the submillimolar range did not potentiate channel activity, and that very high levels of intraluminal Ca (> or = 10 mM) decreased channel open probability 5-10-fold. When InsP3R were measured with Ba as a current carrier in the presence of 110 mM cis potassium, a PBa/PK of 6.3 was estimated from the extrapolated value for the reversal potential. When the unitary current through the InsP3R at 0 mV was measured as a function of the permeant ion (Ba) concentration, the half-maximal current occurred at 10 mM trans Ba. The following conclusions are drawn from these data: (a) the conduction properties of InsP3R are similar to the properties of the ryanodine receptor, another intracellular Ca channel, and differ dramatically from the properties of voltage-gated Ca channels of the plasma membrane. (b) The estimated size of the Ca current through the InsP3R under physiological conditions is 0.5 pA, approximately four times less than the Ca current through the ryanodine receptor. (c) The potentiation of InsP3R by intraluminal Ca in the submillimolar range remains controversial. (d) A quantitative model that explains the inhibitory effects of high trans Ca on InsP3R activity was developed and the kinetic parameters of InsP3R gating were determined. PMID- 7876827 TI - Effects of voltage perturbation of the lingual receptive field on chorda tympani responses to Na+ and K+ salts in the rat: implications for gustatory transduction. AB - Taste sensory responses from the chorda tympani nerve of the rat were recorded with the lingual receptive field under current or voltage clamp. Consistent with previous results (Ye, Q., G. L. Heck, and J. A. DeSimone. 1993. Journal of Neurophysiology. 70:167-178), responses to NaCl were highly sensitive to lingual voltage clamp condition. This can be attributed to changes in the electrochemical driving force for Na+ ions through apical membrane transducer channels in taste cells. In contrast, responses to KCl over the concentration range 50-500 mM were insensitive to the voltage clamp condition of the receptive field. These results indicate the absence of K+ conductances comparable to those for Na+ in the apical membranes of taste cells. This was supported by the strong anion dependence of K salt responses. At zero current clamp, the potassium gluconate (KGlu) threshold was > 250 mM, and onset kinetics were slow (12 s to reach half-maximal response). Faster onset kinetics and larger responses to KGlu occurred at negative voltage clamp (-50 mV). This indicates that when K+ ion is transported as a current, and thereby uncoupled from gluconate mobility, its rate of delivery to the K+ taste transducer increases. Analysis of conductances shows that the paracellular pathway in the lingual epithelium is 28 times more permeable to KCl than to KGlu. Responses to KGlu under negative voltage clamp were not affected by agents that are K+ channel blockers in other systems. The results indicate that K salt taste transduction is under paracellular diffusion control, which limits chemoreception efficiency. We conclude that rat K salt taste occurs by means of a subtight junctional transducer for K+ ions with access limited by anion mobility. The data suggest that this transducer is not cation selective which also accounts for the voltage and amiloride insensitive part of the response to NaCl. PMID- 7876828 TI - Differences in calcium homeostasis between retinal rod and cone photoreceptors revealed by the effects of voltage on the cGMP-gated conductance in intact cells. AB - We measured currents under voltage clamp in intact retinal rod photoreceptors with tight seal electrodes in the perforated patch mode. In the dark, membrane depolarization to voltages > or = +20 mV activates a time- and voltage-dependent outward current in the outer segment. This dark voltage-activated current (DVAC) increases in amplitude with a sigmoidal time course that is voltage dependent. DVAC reaches its maximum enhancement of approximately 30% in 4-6 s at +60 mV. DVAC is entirely suppressed by light and its current-voltage curve and reversal potential are the same as those of the photocurrent. Therefore, DVAC arises from the opening in darkness of the cGMP-gated channels of the outer segment. DVAC is blocked by BAPTA loaded into the cell's cytoplasm and is enhanced by lowering extracellular Ca2+ concentration. Because the cGMP-gated channels are not directly gated by voltage and because BAPTA blocks DVAC, we suggest this signal arises from a voltage-dependent decrease in cytoplasmic Ca2+ concentration that, in turn, activates guanylyl cyclase and causes cGMP synthesis. In rods loaded with high cytoplasmic Na+, membrane depolarization in darkness to voltages > or = +20 mV inactivates the outward current in the outer segment with an exponential time course. We call this DVIC (dark, voltage-inactivated current). DVIC reflects voltage-dependent closing of the cGMP-gated channel in the dark. DVIC, too, is blocked by cytoplasmic BAPTA, and it arises from a voltage-dependent rise in cytoplasmic Ca2+ in darkness, which occurs only if cytoplasmic Na is high. We develop a quantitative model to calculate the rate and extent of the voltage dependent change in cytoplasmic Ca2+ concentration in a normal rod. We assume that this concentration is controlled by the balance between Ca2+ influx through the cGMP-gated channels and its efflux through a Na+/Ca2+, K+ exchanger. Lowered cytoplasmic Ca2+ is linked to guanylyl cyclase activation with characteristics determined from biochemical studies. The model considers the cytoplasmic buffering of both Ca2+ and cGMP. Simulated data generated by the model fit well DVAC measured in rods and also DVAC previously measured in cones. DVAC in cones is larger in magnitude and faster in time course than that in rods. The successful fit of DVAC by the model leads us to suggest that the activity and Ca2+ dependence of the enzymes of transduction are not different in rods and cones, but the quantitative features of Ca2+ homeostasis in the outer segment of the two receptor types differ profoundly.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7876829 TI - Differential effects of pertussis toxin on the muscarinic regulation of Ca2+ and K+ currents in frog cardiac myocytes. AB - The ability of acetylcholine (ACh) to inhibit beta-agonist stimulated calcium current was compared to its ability to activate the inwardly rectifying potassium current IK(ACh) in frog atrial myocytes. As suggested by previous studies, ACh inhibited the calcium current at concentrations (EC50 = 8 nM) significantly lower than those required for the activation of IK(ACh) (EC50 = 101 nM). The pharmacological profiles of the two responses suggest that despite the differences in agonist sensitivity, both are mediated by the same (m2) type of muscarinic receptors. Intracellular application of GDP beta S, an inhibitor of G protein function, completely abolished both responses, implying that both actions of ACh are coupled to effectors by G proteins. In contrast, intracellular application of pertussis toxin (PTX) shifted to higher concentrations (EC50 = 170 nM) but did not abolish inhibition of the calcium current by ACh even though the block of the IK(ACh) response was complete. Increasingly large PTX concentrations and/or prolonged PTX treatments revealed a limiting, PTX-resistant inhibitory component that appears to be mediated by a PTX-insensitive G protein distinct from that mediating IK(ACh). For the PTX-sensitive components, the different agonist dependencies of IK(ACh) activation and calcium current inhibition may imply that different G proteins mediate each response although alternate possibilities involving the same G protein either functionally sequestered and/or differentially affected by interactions with effectors, can not be ruled out. PMID- 7876830 TI - Heterologous expression of BI Ca2+ channels in dysgenic skeletal muscle. AB - We have examined the ability of BI (class A) Ca2+ channels, cloned from rabbit brain, to mediate excitation-contraction (E-C) coupling in skeletal muscle. Expression plasmids carrying cDNA encoding BI channels were microinjected into the nuclei of dysgenic mouse myotubes grown in primary culture. Ionic currents and intramembrane charge movements produced by the BI channels were recorded using the whole-cell patch-clamp technique. Injected myotubes expressed high densities of ionic BI Ca2+ channel current (average 31 pA/pF) but did not display spontaneous contractions, and only very rarely displayed evoked contractions. The expressed ionic current was pharmacologically distinguished from the endogenous L type current of dysgenic skeletal muscle (Idys) by its insensitivity to the dihydropyridine antagonist (+)-PN 200-110. Peak BI Ca2+ currents activated with a time constant (tau a) of approximately 2 ms and inactivated with a time constant (tau h) of approximately 260 ms (20-23 degrees C). The time constant of inactivation (tau h) was not increased by substituting Ba2+ for Ca2+ as charge carrier, demonstrating that BI channels expressed in dysgenic myotubes do not undergo Ca(2+)-dependent inactivation. The average maximal Ca2+ conductance (Gmax) produced by the BI channels was quite large (approximately 534 S/F). In contrast, the average maximal charge movement (Qmax) produced in the same myotubes (approximately 2.7 nC/microF) was quite small, being barely larger than Qmax in control dysgenic myotubes (approximately 2.3 nC/microF). Thus, the ratio Gmax/Qmax for the BI channels was considerably higher than previously found for cardiac or skeletal muscle L-type Ca2+ channels expressed in the same system, indicating that neuronal BI Ca2+ channels exhibit a much higher open probability than these L-type Ca2+ channels. PMID- 7876831 TI - Coordination ability of digalactosamine, and di- and trigalacturonic acids. Potentiometric and spectroscopic studies of Cu(II) complexes. AB - Potentiometric and spectroscopic (EPR, CD, and absorption spectra) data obtained for digalactosamine and di- and trigalacturonic acid with Cu(II) have shown that the di-sugar binding is usually less efficient than that of monomeric units while the tri-sugar can probably simultaneously use two terminal subunits to coordinate a metal ion. The latter result may have some relevance for metal binding by polysaccharides. All sugar ligands use amino or carboxylate functions as an anchor site, as in monomeric units. Bulky oligomeric ligands protect formation of the bis complexes. This causes the hydrolysis to be a dominant process at higher pH. PMID- 7876832 TI - Release of iron from C-terminal monoferric transferrin to phosphate and pyrophosphate at pH 5.5 proceeds through two pathways. AB - Iron release fro C-terminal monoferric transferrin at pH 5.5 and 37 degrees C was studied as a function of chloride, phosphate, and pyrophosphate concentration. The rate constant for iron release depends linearly on chloride concentration, confirming that anion binding is mandatory for iron release, not only at pH 7.4 as has been previously reported, but also at pH 5.5. The extent of iron release is relatively small (< 20% for 1.0 M chloride). Concentrations of > 0.2 M phosphate are required for complete iron removal, but millimolar concentrations of pyrophosphate effect complete removal. The observed rate constants for iron release to phosphate and pyrophosphate change from one linear dependence to another less steep linear dependence on the concentration of these ligands, providing quantitative evidence that the two-pathway mechanism that we previously proposed for iron release at pH 7.4 persists at pH 5.5. According to this model, the pathway of iron release is determined by the nature of the anion occupying a kinetically significant anion binding site on the protein. The qualitative similarity of the current data with that recently reported for iron release from the transferrin-transferrin receptor complex provides strong support for the contention that the two-pathway mechanism also persists in this complex at low pH and is hence likely to be operative in vivo. PMID- 7876833 TI - The effect of lithium therapy upon the composition of the human erythrocyte membrane. AB - The membrane phospholipids and membrane proteins from the erythrocytes of manic depressive patients undergoing lithium therapy and of normal controls were examined by high performance TLC and gel electrophoresis, respectively. The phospholipid composition of the erythrocyte membranes of the normal controls was close to that reported previously. The lipid composition of the erythrocyte membranes of the patients was very similar but differed from the normal controls in that the proportion of sphingomyelin and cholesterol appeared to be lower, whereas phosphatidylserine appeared to be higher in the patients by amounts comparable with the sums of the 95% confidence limits on the measurements. No major differences in the protein composition of the erythrocyte membranes were detected. PMID- 7876834 TI - Antimicrobial and genotoxic activity of 2,6-diacetylpyridine bis(acylhydrazones) and their complexes with some first transition series metal ions. X-ray crystal structure of a dinuclear copper(II) complex. AB - The antibacterial and antifungal properties of five 2,6-diacetylpyridine bis(acylhydrazones) (acyl:benzoyl, H2dapb; 2-aminobenzoyl, H2dapab; salicyloyl, H2daps; picolinoyl, H2dappc; 2-thenoyl, H2dapt) and of a series of metal complexes were investigated. The x-ray crystal structure of the [Cu(dapt)]2 complex was also determined. It consists of dimeric units in which both copper atoms have sixfold coordination. The evaluation of in vitro antimicrobial properties showed some compounds to exhibit good activity against Gram positive bacteria. In most cases, complexes showed a similar or reduced activity as compared to the ligand itself. Only the iron complexes were found to be more active than the chelating agent involved. None of the compounds showed any significant antifungal activity. The genotoxicity of the compounds described was studied in vitro with Bacillus subtilis rec-assay and Salmonella-microsome reversion assay. No DNA-damaging activity was detected in the Bacillus subtilis rec-assay. H2dapb, H2dapb, and H2dappc were active in the Salmonella test. In several cases, the genotoxic properties of the ligands disappeared in the complexes. PMID- 7876835 TI - Comment on self-similarity of Mn(II)-induced trypsin activity oscillations. Experimental evidence [1]. PMID- 7876836 TI - Monomeric Pseudomonas aeruginosa nitrite reductase: preparation, characterization, and kinetic properties. AB - Monomeric nitrite reductase in an active form has been prepared by controlled succinylation of the dimeric native enzyme of Pseudomonas aeruginosa and subsequent purification. The monomeric enzyme has an optical spectrum indistinguishable from that of the native enzyme. On the other hand, circular dichroic spectra in the heme and peptide absorption regions show differences with respect to the dimer that indicate that the chemical modification and/or the dissociation into monomers somewhat perturb the chromophores' environment and the secondary structure. The (negatively charged) monomer is unable to oxidize its physiological substrates, azurin and cytochrome c551. This loss of activity is not due to monomerization, but is linked to the total net charge of the succinylated molecule, which interestingly enough acquires the ability to oxidize efficiently eukaryotic cytochrome c (which is not a substrate of the native dimeric enzyme). Stopped-flow studies show that the reduced monomer reacts with oxygen with a kinetic pattern similar to that shown by the dimeric enzyme. However, a higher reaction rate in the bimolecular binding of oxygen and a much higher oxygen affinity than for the native enzyme are observed. The evidence reported in this paper indicates that the dimeric state of Pseudomonas nitrite reductase is not a prerequisite for the ferrocytochrome c-oxygen oxidoreductase activity of this enzyme. PMID- 7876837 TI - Copper(II) interactions with nonsteroidal antiinflammatory agents. I. Salicylic acid and acetylsalicylic acid. AB - Recently a growing body of evidence has accumulated on the beneficial effects of copper compounds toward various models of inflammation, and copper complexes of nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to be more effective in this respect than the parent agents. However, the origin of this activity remains unclear: The ability of NSAIDs to influence copper metabolism is still questionable, and apart from the claimed SOD-like activity of copper salts in vivo, relatively little is known about how copper-NSAID interactions may help regulate the inflammatory process. Before the potential role of copper-NSAID complexes versus inflammation can be elucidated, speciation studies are necessary (i) to analyze the overall influence of these drugs on copper metabolism and (ii) to discriminate the individual complexes likely to represent the active form of the drug in vivo. In this paper, copper(II) complex equilibria with salicylic and acetylsalicylic acids--and benzoic acid used as a reference--as well as the mixed ligand complex equilibria generated by these binary systems and L-histidine [main low-molar-mass ligand of copper(II) in blood plasma] have been investigated under physiological conditions (37 degrees C; 0.15-M NaCl). Confirming previous observations by others, resulting simulated plasma copper distributions virtually rule out any quantitative influence of salicylate on copper tissue diffusion at therapeutic levels. Even though, as is presently shown, both salicylate and acetylsalicylate may favor the gastrointestinal absorption of copper, it seems unlikely that salicylate can exert its antinflammatory activity predominantly through copper complexation. The assertion that copper-NSAID complexes represent the active forms of NSAIDs therefore seems to be of limited significance for salicylate. PMID- 7876838 TI - Unsymmetrical borole complexes as biocides: synthetic, structural and biological aspects. AB - Triisopropoxyborane on treatment with catechol in equimolar ratio in excess of benzene affords the formation of 2-isopropoxybenzo-1,3-dioxa-2-borole [OC6H4OB(OPri)]. The interaction of [OC6H4OB(OPri)] with benzothiazolines, prepared by the condensation of [1-(2-thienyl)ethanone], [1-(2 pyridinyl)ethanone], [1-(2-furanyl)ethanone], and [1-(2-naphthenyl)ethanone] with 2-mercaptoaniline, yields complexes that have B--O, B--S, and B<--N bonds. The unsymmetrical borole complexes were subjected to microestimations and spectral analyses comprised of UV, IR, proton-1, boron-11, and carbon-13 nuclear magnetic resonance studies. The spectral studies point to a tetracoordinated environment around boron because the stereochemically active lone pair is also included in the coordination sphere. X-ray powder diffraction of a representative complex also has been carried out. In the quest for better fungicides and bactericides, studies were conducted to assess the growth-inhibiting potential of the synthesized complexes along with the ligands against various fungal and bacterial strains. The studies demonstrate that the concentrations reach levels that are sufficient to inhibit and kill the pathogens. Furthermore, the results achieved from biological activity also have been compared with the conventional fungicide, Bavistin, and conventional bactericide, Streptomycin. PMID- 7876839 TI - Metal complexes of the carbonic anhydrase inhibitor methazolamide (Hmacm). Crystal structure of the Zn(macm)2(NH3)2. Anticonvulsant properties of the Cu(macm)2(NH3)3(H2O). AB - Complexes of Co(II), Cu(II), and Zn(II) with deprotonated methazolamide and ammonia are synthesized and characterized. The complex Zn(macm)2(NH3)2 crystallizes in the monoclinic C2/c space group with a = 13.468(1), b = 6.759(1), c = 23.014(2) A, beta = 90.27(1), and Z = 4. The structure was refined to R = 0.049 (Rw = 0.053). The Zn(II) ion is coordinated to two deprotonated sulfonamido nitrogen atoms of the macm- ligand and two nitrogen atoms of the ammonia ligands in a distorted tetrahedron. The Zn(macm)2(NH3)2 complex is shown to be a simple model for the methazolamide inhibition of CA. EHMO calculations applied to fractional coordinates of the Zn(macm)2(NH3)2 complex indicate that the atomic orbitals of the Zn do not contribute to HOMO and LUMO of the complex. The characteristics of the Cu(macm)2(NH3)3(H2O) as an anticonvulsant agent are tested. PMID- 7876840 TI - Stroke in pregnancy and the puerperium: what magnitude of risk? PMID- 7876843 TI - Neurological stamp. Humulus lupulus (hop). PMID- 7876842 TI - Cerebral blood flow and metabolism in children with severe head injury. Part 1: Relation to age, Glasgow coma score, outcome, intracranial pressure, and time after injury. AB - Understanding the pathophysiology of paediatric head trauma is essential for rational acute management. It has been proposed that the response to severe head injury in children differs from that in adults, with increased cerebral blood flow (cerebral hyperaemia) representing the most common cause of raised intracranial pressure, but this has recently been disputed. The relation between the pathophysiological response and time after injury has not been defined in children. This paper describes 151 serial measurements of cerebral blood flow, arteriojugular venous oxygen difference (AJVDO2), and cerebral metabolic rate for oxygen (CMRO2) that were performed in 21 children with severe head injury, mean age 8 (range 2-16) years, Glasgow coma score < or = 8. Absolute cerebral hyperaemia was uncommon, only 10 (7%) of the 151 cerebral blood flow values being at or above the upper limit of the range published in normal children. There was an inverse correlation between cerebral blood flow and intracranial pressure. (r = -0.24, p = 0.009). Contrary to the widespread assumption that cerebral metabolic rate in patients with head injury is always low, CMRO2 was initially within the normal range in 17/21 (81%) children. Both CMRO2 and AJVDO2 fell significantly between the first and third days after injury. There was a non significant rise in cerebral blood flow over time. These data represent the first evidence that the temporal change in cerebral metabolic rate reported in experimental models of traumatic brain injury also occurs in patients with head injury. The changes in the pathophysiological response over time suggest that the management may need to be modified accordingly. If cerebral metabolic rate and cerebral oxygen extraction are maximal shortly after injury in children with severe head injury then the children are most likely to sustain secondary damage during this period. PMID- 7876841 TI - Imaging the head: functional imaging. PMID- 7876844 TI - Cerebral blood flow and metabolism in children with severe head injuries. Part 2: Cerebrovascular resistance and its determinants. AB - It has been proposed that in children with severe head injuries the cerebral circulation does not respond appropriately to normal physiological control mechanisms, making children more susceptible than adults to low cerebrovascular resistance, increased cerebral blood flow (cerebral hyperaemia), and raised intracranial pressure. To investigate this issue, 122 serial measurements of cerebrovascular resistance in 17 children with severe head injuries have been performed and related to cerebral perfusion pressure, arterial CO2 (PaCO2), arterial oxygen content (AO2), and the cerebral metabolic rate of oxygen (CMRO2). Cerebrovascular resistance values (mean (SD) 1.54 (0.61) mm Hg.ml-1.100 g.min) were normal or raised in most cases; 71 values (58%) were within the normal range, 39 (32%) above the upper limit, and only 12 (10%) below the lower limit. There was a significant correlation between cerebral perfusion pressure and cerebrovascular resistance (r = 0.32, p = 0.0003), suggesting preservation of pressure autoregulation. This correlation was absent in four of the five children who died or survived with severe handicap. Analysis by multilevel modelling indicated that, as in normal subjects, CMRO2, CPP, AO2, PaCO2, and cerebrovenous pH were important independent determinants of cerebrovascular resistance. The results indicate that normal cerebrovascular reactivity is often preserved in children with severe head injuries but may be impaired in the most severely injured patients. PMID- 7876845 TI - Clinicopathological study of 35 cases of multiple system atrophy. AB - The clinical and pathological features of 35 cases with multiple system atrophy collected in the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) between 1985 and 1992 have been analysed. The median age of onset was 55 (range 33.3-75.8) years and median survival was 7.3 (range 2.1-11.5) years. Parkinsonism, usually asymmetric, occurred in all, and autonomic failure in all but one case. Cerebellar signs were noted in 34% and pyramidal features in 54% of the cases. Glial cytoplasmic inclusions were found in all cases with adequate fixation. Lewy bodies were detected in three cases. The substantia nigra was (usually severely) depleted of cells in all cases. With two exceptions the putamen was atrophic; the caudate and pallidum were less commonly and less severely affected. Overall nigrostriatal cell loss correlated with severity of disease at the time of death. The latest, but not the best, recorded levodopa response tended to be inversely related to the degree of putaminal degeneration. The olivopontocerebellar system was involved in 88% of the cases, the cerebellar vermis usually being more severely affected than the hemispheres. The presence of associated cerebellar pathology was, however, unrelated to the presence of cerebellar signs in life. PMID- 7876846 TI - Progressive supranuclear palsy: neuropathologically based diagnostic clinical criteria. AB - All cases examined postmortem at the Mayo Clinic that met the classic neuropathological criteria for progressive supranuclear palsy (PSP) were identified for retrospective clinical analyses. The necropsy material was re examined by a second neuropathologist to confirm the pathological diagnosis of PSP, yielding 12 cases. A range of clinical signs were documented in these patients, with numerous findings beyond those noted in the original descriptions of this disorder. Atypical clinical findings included absence of supranuclear gaze palsy (two cases), prominent asymmetry (two), arm dystonia (two), upper limb apraxia (two), myoclonus (two), chorea (one), eyelid opening apraxia (one), and respiratory disturbance (one). A definite clinical diagnosis of PSP had been made during life in only eight of the 12 patients. From the retrospective analysis of these 12 cases, a set of clinical criteria were developed for the premortem diagnosis of PSP emphasising differences from other akinetic-rigid disorders. PMID- 7876847 TI - Neuropsychological pattern of striatonigral degeneration: comparison with Parkinson's disease and progressive supranuclear palsy. AB - To study the neuropsychological pattern of striatonigral degeneration (SND), 14 consecutive patients with probable SND were submitted to an extensive battery of neuropsychological tests. Compared with controls the performance of patients with SND was impaired on category and phonemic fluency, frontal behaviours, trail making test A and B, and free recall of the Grober and Buschke test, but normal on the revised WAIS verbal scale, Raven 47 coloured progressive matrices, Wechsler memory scale, California verbal learning test, Wisconsin card sorting test, and the Stroop interference condition. The performance of patients with SND was also compared with that of 14 patients with Parkinson's disease and 14 patients with progressive supranuclear palsy (PSP) matched for age at onset, duration of disease, severity of intellectual deterioration, and depression. The results showed that the dysexecutive syndrome of SND is similar to that of Parkinson's disease and less severe than in PSP. PMID- 7876848 TI - Progressive spinocerebellar degeneration "plus" associated with Langerhans cell histiocytosis: a new paraneoplastic syndrome? AB - Langerhans cell histiocytosis (LCH), formerly known as histiocytosis-X, manifests by granulomatous lesions consisting of mixed histiocytic and eosinophilic cells. The hallmark of LCH invasion into the CNS is diabetes insipidus, reflecting local infiltration of Langerhans cells into the posterior pituitary or hypothalumus. In five patients who had early onset LCH with no evidence of direct invasion into the CNS, slowly progressive spinocerebellar degeneration accompanied in some by pseudobulbar palsy and intellectual decline was seen. Neurological impairment started 2.5 to seven years after the detection of LCH. No correlation was found between the clinical syndrome and location of LCH or its mode of treatment. An extensive search for metabolic, toxic, neoplastic, and hereditary aetiologies for progressive cerebellar degeneration was negative. It seems that the clinical entity described here may be considered a new paraneoplastic syndrome related to LCH. It may be induced by the eosinophil derived neurotoxin, which was shown to cause damage to Purkinje cells and pyramidal neurons. PMID- 7876849 TI - Advance information and movement sequencing in Gilles de la Tourette's syndrome. AB - Tourette's syndrome is a chronic neurological disorder manifested by involuntary motor tics and vocalisations. Because the basal ganglia have been implicated in the pathology underlying Tourette's syndrome, the present two procedures, both involving sequential movements, sought to determine the extent to which patients with Tourette's syndrome were reliant on, and could utilise different levels of advance information. Patients with Tourette's syndrome were found to be more reliant than controls on external visual cues to execute rather than to initiate a motor programme. When there was a high level of reduction in advance information--that is, a visual pathway to be followed was extinguished well in advance of each successive movement--executions progressively slowed as the sequence was traversed. Similarly, if no advance information was provided before each move, movement execution was slower than that of controls. The movement initiation times of patients with Tourette's syndrome were, however, similar to those of controls, as were their movement execution times when advance visual information was available. It seems that patients with Tourette's syndrome, like parkinsonian patients who are known to have a basal ganglia disorder, require external sensory cues to sequence a motor programme effectively. The present study found evidence consistent with the hypothesis that patients with Tourette's syndrome, like patients with Parkinson's disease, may be dysfunctional in internal switching mechanisms. Alternatively, with limited visual guidance, patients with Tourette's syndrome, regardless of medication or depression state, may require more time to plan and programme each next submovement, and under such conditions may require external visual cues to direct attention effectively to given targets. Although the underlying pathogenesis is still speculative, it is concluded that there is much to support the notion that Tourette's syndrome may stem from abnormalities of the major pathways between the basal ganglia and the frontal lobes. PMID- 7876850 TI - Some speech disorders. PMID- 7876851 TI - Impaired prepulse inhibition of acoustic and tactile startle response in patients with Huntington's disease. AB - The corpus striatum serves a critical function in inhibiting involuntary, intrusive movements. Striatal degeneration in Huntington's disease results in a loss of motor inhibition, manifested by abnormal involuntary choreiform movements. Sensorimotor inhibition, or "gating", can be measured in humans using the startle reflex: the startle reflex is normally inhibited when the startling stimulus is preceded 30-500 ms earlier by a weak prepulse. In the present study, prepulse inhibition (PPI) was measured in patients with Huntington's disease to quantify and characterise sensorimotor gating. Compared with age matched controls, patients with Huntington's disease exhibit less PPI. Startle gating deficits are evident in patients with Huntington's disease when startle is elicited by either acoustic or tactile stimuli. Even with stimuli that elicit maximal PPI in normal subjects, patients with Huntington's disease exhibit little or no PPI, and their pattern of startle gating does not show the normal modulatory effects usually elicited by changing the prepulse interval or intensity. Startle amplitude and habituation and latency facilitation are largely intact in these patients, although reflex latency is significantly slowed. In patients with Huntington's disease, startle reflex slowing correlates with cognitive impairment measured by the dementia rating scale, and with the performance disruptive effects of interference measured by the Stroop test. These findings document a profound disruption of sensorimotor gating in patients with Huntington's disease and are consistent with preclinical findings that identify the striatum and striatopallidal GABAergic efferent circuitry as critical substrates for sensorimotor gating of the startle reflex. PMID- 7876852 TI - Continuous response variable trial design in motor neuron disease: long term treatment with a TRH analogue (RX77368). AB - The continuous response variable controlled trial design is developed as a model for the efficient screening of candidate treatments in motor neuron disease. A TRH analogue (RX77368) and placebo were randomly allocated to 15 matched pairs of patients with motor neuron disease. With validated composite interval scores, this trial excluded a 50% or greater improvement with RX77368 at month 12 in scores of respiratory, lower limb, and activities of daily living function with greater than 90% power, and in bulbar function scores with 80% power. For upper limbs, 52% and 75% improvements were excluded at months 9 and 12 respectively with 80% power. Patients who died during the study had faster deterioration rates in bulbar and respiratory scores than their surviving pairs. The feasibility of screening drugs for significant biological effects with small sample sizes and good statistical power is shown. The difficulties of handling deaths and dropouts when using this design are discussed. Comparisons are made with sample sizes required using other scores and rating scales, as well as with those required in hazard and event rate studies. A simple clinical grading scale for motor neuron disease, with its corresponding composite interval scores, is described. PMID- 7876853 TI - Rhabdomyolysis and acute encephalopathy in late onset medium chain acyl-CoA dehydrogenase deficiency. AB - A previously asymptomatic 30 year old man presented with rhabdomyolysis, muscle weakness, and acute encephalopathy after strenuous exertion in the cold without adequate food intake. Serum and muscle carnitine concentrations were decreased. Urinary excretion of carnitine and glycine esters and biochemical examination of skeletal muscle and fibroblasts led to the diagnosis of medium chain acyl-CoA dehydrogenase (MCAD) deficiency. A point mutation at nucleotide position 985 of the coding region of the MCAD gene was found. The MCAD protein was synthesised in the patient's fibroblasts at a normal rate, but was unstable. In general, patients in whom the 985 point mutation has been established show much more severe clinical symptoms and other symptoms than those seen in this patient. The relation of the 985 point mutation and the residual MACD activity to the symptoms is not as straightforward as previously thought. PMID- 7876854 TI - Pholedrine: a substitute for hydroxyamphetamine as a diagnostic eyedrop test in Horner's syndrome. AB - Mydriatic responses to eyedrops containing the indirect acting sympathomimetic amines tyramine, hydroxyamphetamine, and pholedrine have been compared in 10 healthy subjects. Pholedrine, the n-methyl derivative of hydroxyamphetamine, at a concentration of 1% had effects similar to those produced by 0.5% hydroxyamphetamine itself. Pretreatment with topical guanethidine attenuated its responses and in 13 patients with unilateral Horner's syndrome it distinguished clearly those five patients who had preganglionic from the eight with postganglionic lesions. It is concluded that 1% pholedrine may be substituted for 0.5% hydroxyamphetamine, which is no longer available, as a diagnostic agent for use in Horner's syndrome. PMID- 7876855 TI - Loss of heterozygosity for DNA polymorphisms mapping to chromosomes 10 and 17 and prognosis in patients with gliomas. AB - Twenty nine patients with gliomas were investigated for loss of heterozygosity for 40 DNA polymorphisms in tumour DNA, particularly concentrating on those mapping to chromosomes 10 and 17. Eight of 18 grade IV gliomas showed loss of sequences from chromosomes 10, 17, or both. The data suggested total loss of one copy of chromosome 10, but there were interstitial deletions of the short arm of chromosome 17 in three of five tumours. Heterogeneous interstitial deletions of chromosome 17 were also found in two lower grade astrocytomas and one benign oligodendroglioma. The striking finding of this study was that patients with high grade gliomas whose tumours exhibited loss of heterozygosity for chromosomes 10, 17, or both survived significantly longer after surgery (median 17.4 months) than those whose tumours did not show loss of these chromosomes (median 6.7 months). These findings suggest that there is a subset of particularly aggressive high grade gliomas with no currently known molecular genetic abnormalities. PMID- 7876856 TI - Partial restoration of blink reflex function after spinal accessory-facial nerve anastomosis. AB - Functional motor control requires perfect matching of the central connections of motoneurons with their peripheral inputs. It is not known, however, to what extent these central circuits are influenced by target muscles, either during development or after a lesion. Surgical interventions aimed at restoring function after peripheral nerve lesions provide an opportunity for studying this interaction in the mature human nervous system. A patient was studied in whom the spinal accessory nerve was anastomosed into a lesioned facial nerve, allowing voluntary contractions of the previously paralysed muscles. This procedure, in addition to replacing the facial neurons at peripheral synapses, allowed a new short latency trigeminospinal accessory reflex of the R1 blink reflex type to be demonstrated, implying that trigeminal neurons had sprouted towards spinal accessory motoneurons over a distance of at least 1 cm. These results show an unexpected influence of the periphery in remodelling central connectivity in humans. The motoneuronal excitability for this R1 reflex response was therefore studied to compare the convergent properties of facial motoneurons (normal side) with those of the spinal accessory motoneurons (operated side) using a classic double shock technique with variable interstimulus intervals (conditioning test stimulus). On the normal side, conditioning stimuli (to the ipsilateral or contralateral infraliminar supraorbital nerve) produced a clearcut facilitation of the R1 blink reflex when the interstimulus interval was 30-80 ms. By contrast, a similar procedure had no effect on the R1 blink reflex mediated via the trigeminal-spinal accessory reflex arc. These data indicate that despite the heterotopic sprouting of some axons from neurons in the XIth nucleus, motoneurons involved in the newly formed reflex arc remain totally inexcitable by other trigeminal afferents and seem unable to ensure a physiological functioning of the normal blink reflex. Thus the functional relevance of the recovered R1 blink response remains unclear. PMID- 7876857 TI - Thrombolytic treatment for acute occlusion of the basilar artery. AB - Sixteen patients with acute occlusion of the basilar artery were treated with systemic fibrinolysis. Recanalisation was achieved in 10 patients; five patients survived and 11 patients died. Survival was associated with vascular recanalisation in every case. Most of the survivors were younger than 50. An age above 50 and a comatose state on admission seem to indicate a poor clinical outcome. The problem of multimorbidity in the older age group also affects outcome adversely. Haemorrhagic complications were found in two cases (12.5%), with clinical deterioration in one. PMID- 7876858 TI - A missense point mutation (Ser515Phe) in the adrenoleukodystrophy gene in a family with adrenomyeloneuropathy: a clinical, biochemical, and genetic study. AB - A 36 year old male patient with adrenomyeloneuropathy (AMN) developed progressive spastic paraparesis and sensory ataxia from the age of 18. Biochemical studies showed increased plasma concentrations of saturated very long chain fatty acids (VLCFAs), subclinical evidence of adrenal insufficiency, and primary hypogonadism. Three female family members had increased plasma concentrations of VLCFAs, suggesting carrier status of adrenoleukodystrophy (ALD). Molecular genetic analysis detected a missense point mutation (C1930T) in exon 6 within the ALD gene, which predicts substitution of an amino acid (Ser515Phe) that is conserved between the deduced amino acid sequence of the peroxisomal membrane protein PMP70 and ALD protein. Detection of this point mutation allows diagnosis of ALD or AMN, identification of heterozygotes, and prenatal diagnosis of ALD. PMID- 7876859 TI - Treatment of chronic limb spasticity with botulinum toxin A. AB - The purpose of this open study was to find out whether botulinum toxin A (BTX-A) relieves the signs and symptoms of chronic limb spasticity. The study comprised 40 patients, aged 12-82 years, with moderate to severe spasticity of the upper (13) or lower limbs (27) refractory to conventional physical and medical treatments. Outcome measures were clinical and blinded videotape assessments of spasticity and motor function. Electromyography guided BTX-A injections were given in one or two sessions at total doses averaging 175 U in the upper limb (range 70-270 U) and 221 U in the lower limb (range 100-500 U). Thirty four patients (85%) derived worthwhile benefit, with improved limb posture and increased range of passive motion in 31, pain reduction in 28 of 31 with pain, and improved function in 16. Side effects were limited to local and usually mild discomfort from the injections (19), symptomatic local weakness (one), and local infection (one). Preliminary experience indicates that BTX-A is a promising adjunctive treatment for selected patients with spasticity. PMID- 7876860 TI - "Pseudo" hypertrophic neuropathy of childhood. AB - A 9 year old boy had chronic progressive motor-sensory neuropathy that started in early infancy. He had enlarged nerves and pes cavus deformity. Motor conduction studies showed very dispersed, polyphasic compound muscle action potentials with conduction velocities around 2 m/s. A sural nerve biopsy showed severe loss of myelinated fibres. Two months of treatment with corticosteroids restored muscle power. During this time the enlarged nerves became normal and electrophysiological recovery was achieved. Chronically acquired neuropathy in infancy is strikingly similar to genetically determined neuropathy. PMID- 7876862 TI - Miller Fisher-Guillain-Barre overlap syndrome with enhancing lesions in the spinocerebellar tracts. AB - The site of lesions in Miller Fisher syndrome, especially those causing ataxia, has been controversial. A 50 year old man with features of Miller Fisher syndrome in whom MRI showed enhancing lesions in the spinocerebellar tracts at the level of the lower medulla is reported. Peripheral involvement of cranial nerves was also indicated by an abnormal blink reflex and by clinical manifestations: complete external ophthalmoplegia, bilateral peripheral facial weakness, convergence disturbance, absence of Bell's phenomenon, oculocephalic, and oculovestibular reflex. Abnormal lesions on MRI disappeared and the blink reflex became normal with clinical improvement. The case is regarded as Miller Fisher Guillain-Barre overlap syndrome, a postinfectious allergic reaction involving both peripheral nerves in the cranium and neuraxis in the spinocerebellar tract. The lesions in the spinocerebellar tracts are responsible for cerebellar ataxia in this syndrome. PMID- 7876861 TI - Erdheim-Chester disease and slowly progressive cerebellar dysfunction. AB - A 59 year old woman developed pronounced thirst, increased water intake, and increased urinary output followed by slowly progressive cerebellar symptoms. Brain MRI showed abnormal hyperintensity on T2 weighted studies in the region of both dentate nuclei without atrophy of the cerebellum or the brainstem. A 99mTC diphosphonate bone scan showed bone lesions in the distal parts of both femurs as well as distal and proximal parts of both tibias. The diagnosis of Erdheim Chester disease was made by bone biopsy. This is the first case of Erdheim Chester disease presenting as a slowly progressive cerebellar syndrome and diabetes insipidus, and also showing high signal lesions in deep cerebellar nuclei on MRI. Skeletal surveys are indicated for patients with otherwise unexplained slowly progressive cerebellar symptoms. PMID- 7876863 TI - Chronic dacryosialadenitis in HTLV I associated myelopathy. AB - A prospective study was carried out on 48 patients with HTLV I associated myelopathy/tropical spastic paraparesis (HAM/TSP) to assess the association between this entity and Sjogren's syndrome. Fourteen patients (29.1%) had chronic dacryosialadenitis confirmed by a positive Schirmer's test and salivary gland biopsy. None of these patients had evidence of collagen disease and tests for Ro, La, and rheumatoid factor were negative except in one case. Therefore, the dacryosialadenitis could not be classified as either primary or secondary Sjogren's syndrome. Ten of the 14 patients (71.4%) had other systems (haematological, articular, dermatological, or respiratory) involved apart from the neurological and exocrine gland pathology. The findings suggest that the dacryosialadenitis associated with HTLV I is a disease of viral origin distinct from Sjogren's syndrome. PMID- 7876864 TI - Single parenchymal brain cysticercus in the acute encephalitic phase: definition of a distinct form of neurocysticercosis with a benign prognosis. AB - Fifty four patients with a single parenchymal brain cysticercus in the acute encephalitic phase were studied to outline the features of this form of the disease. Seizures were the presenting symptom in all cases. Twenty six patients had a single seizure and 28 had several seizures before admission. Neurological examination was normal in 45 patients and showed focal signs in nine. All patients had a single enhancing CT lesion; all but three lesions were < 20 mm. Anticonvulsants were started in every patient. Forty five patients were followed up for 18 (SD 6) months. Thirty seven of these 45 patients received albendazole. Four weeks after the trial, CT showed resolution of lesions in all cases. The remaining eight patients refused albendazole, and CT showed persistence of lesions by 16 weeks in six cases. At the end of the follow up, all patients who received albendazole were free of seizures as opposed to three of eight patients who did not receive the drug. Focal signs improved in the nine patients with these signs (all received albendazole). Recognition of this form of neurocysticercosis permits early treatment with albendazole that greatly improves the prognosis. PMID- 7876865 TI - The use of PET in evaluating patients with primary brain tumours: is it useful? AB - During an 18 month period 39 patients were evaluated with [18F] fluorodeoxyglucose-PET (FDG-PET) for primary brain tumours. These included patients with suspected newly diagnosed tumours and patients with known tumours who were being evaluated for possible recurrence or increasing tumour grade. Scans were performed on a 951-31 Siemen's PET scanner with 4 mm resolution. Scanning time was about 20 minutes per patient. All patients had undergone recent cerebral MRI. These patients were divided into two groups. In the first group (30) MRI and PET concurred on the diagnosis. The second group (nine) comprised those where the interpretation of MRI and PET was different or there was a question of the diagnosis on MRI. This group comprised three patients in whom MRI suggested recurrent tumour and PET inaccurately suggested radiation necrosis; two patients with newly diagnosed enhancing lesions on MRI in whom PET was useful in distinguishing strokes from tumour; two patients with prior gliomas with new enhancing isolated lesions on MRI in whom PET scan accurately depicted radiation necrosis; and two patients with newly diagnosed enhancing lesions on MRI in whom PET scan was helpful in distinguishing multiple sclerosis from tumour in one but not in the other. Therefore, of the 39 patients, PET was helpful in five in distinguishing tumour from other disease processes; but, in so far as influencing treatment, it seemed helpful in only two. Thus PET seems to be of limited value as an aid to evaluating and treating patients with suspected or known primary brain tumours. PMID- 7876866 TI - Treatment of paroxysmal symptoms in multiple sclerosis with bromocriptine. PMID- 7876867 TI - Onset symptoms of multiple sclerosis. PMID- 7876868 TI - Multiple sclerosis in the Parsis. PMID- 7876869 TI - A new treatment of spasticity with repetitive magnetic stimulation in multiple sclerosis. PMID- 7876870 TI - Patients with clinically definite multiple sclerosis, white matter abnormalities on MRI, and normal CSF: if not multiple sclerosis, what is it? PMID- 7876871 TI - Long term course of change in anti-Yo antibody content in paraneoplastic cerebellar degeneration. PMID- 7876872 TI - Painful paroxysmal dystonia associated with focal epileptic activity. PMID- 7876873 TI - Treatment of spasmodic torticollis with intramuscular phenol injection. PMID- 7876874 TI - Tuberculous myelopathy: a serial MRI study. PMID- 7876875 TI - Bickerstaff's brainstem encephalitis associated with cytomegalovirus infection. PMID- 7876876 TI - Raymond syndrome (alternating abducent hemiplegia) caused by a small haematoma at the medial pontomedullary junction. PMID- 7876877 TI - Pupillary dilatation and arm weakness as negative ictal phenomena. PMID- 7876878 TI - Glial cytoplasmic inclusions are not exclusive to multiple system atrophy. PMID- 7876879 TI - Is visual neglect body-centric? PMID- 7876880 TI - A novel cytochrome P-450IID6 (CYPIID6) mutant gene associated with multiple system atrophy. PMID- 7876881 TI - Complete remission of narcolepsy after surgical treatment of an arachnoid cyst in the cerebellopontine angle. PMID- 7876882 TI - Handicap one year after a stroke: validity of a new scale. PMID- 7876883 TI - Motor neuron disease. PMID- 7876884 TI - Cerebral cortical dysplasia associated with pediatric epilepsy. Review of neuropathologic features and proposal for a grading system. PMID- 7876885 TI - Mucolipidosis IV: morphology and histochemistry of an autopsy case. AB - Mucolipidosis Type IV is a rare, autosomal recessive disorder characterized by corneal opacification, mental retardation, and delayed motor milestones. Whereas lysosomal storage material has been demonstrated in biopsied tissues and leukocytes, the complete autopsy pathology, including neuropathology, is unknown. The metabolic defect remains speculative. We report the general and neuropathologic findings of the only known autopsy. In the central nervous system, neuronal loss in the cerebral cortex, basal ganglia, deep cerebellar nuclei, and brainstem nuclei was marked by astrocytosis; the cytoplasm of residual neurons had brown granules. These granules were positive with periodic acid-Schiff, Concanavalia ensiformis, and Sudan black, but not with Luxol-fast blue. Ultrastructurally, neurons contained lysosomes laden with osmiophilic, amorphous and granular material, and few lamellated membrane structures. Hepatocytes, epithelia, endothelia, chondrocytes, and tissue macrophages also stained positively with Datura stramonium and Ricinus communis-I agglutinins, with renal glomeruli also staining with peanut agglutinin; most non-neural cells contained osmiophilic granules on toluidine blue-stained, plastic embedded sections, corresponding to lamellated membrane structures. These findings complement the previously reported ocular morphology and brain and liver biochemistry performed in the same patient, and suggest that the storage material in neurons differs from that in non-neural cells. Furthermore, the underlying defect is not likely to be a deficiency of a single enzyme (i.e. a lysosomal hydrolase). PMID- 7876886 TI - Retroviral infection (HTLV-I) induces cytokine-regulated immunomodulation and cytotoxicity of medulloblastoma cells. AB - Primitive neuroectodermal tumors are thought to result from disturbed differentiation of neuroepithelial stem cells. These tumor cells retain the capacity to differentiate toward the neuron or glia phenotype under extrinsic stimuli. Previously, we have developed a model for the differentiation of a medulloblastoma cell line (Dev cells) induced by infection with the human retrovirus HTLV-I. This virus delivers signals which trigger the Dev cells to differentiate toward an astrocytic lineage. The aim of this study was to characterize the time course of viral infection, to identify the soluble factors released and to analyze their effects on Dev cells. The early phase of viral replication is followed by latent infection. Viral infection induces glial differentiation in a subpopulation of cells and results in the death of others. The inflammatory cytokines TNF alpha, IL1 alpha and IL6 were detected in medium conditioned by infected Dev cells. TNF alpha was cytotoxic and cytostatic for subpopulations of Dev cells. Furthermore, TNF alpha treatment reproduced the modulation of expression of the major histocompatibility complex antigens (MHC class I) observed in infected Dev cells. These observations support the view that HTLV-I infection, which triggers glial differentiation of medulloblastoma Dev cells, also causes the release of soluble factors capable of downregulating proliferation of dividing tumor cells and of modifying their recognition by cellular immune effectors. PMID- 7876887 TI - Denervated segments of injured skeletal muscle fibers are reinnervated by newly formed neuromuscular junctions. AB - A muscle fiber normally receives its innervation at a single neuromuscular junction (NMJ). Transection of myofiber usually leaves one (abjunctional) stump denervated, while the other (adjunctional) remains innervated. To determine the mechanism of reinnervation of the abjunctional stumps, we transected the rat extensor digitorum muscle (EDL) below the site of the distalmost NMJ. Myofiber regeneration was followed for up to 56 days. Reinnervation began with the appearance of irregular acetylcholinesterase and alpha-bungarotoxin-positive deposits on abjunctional stumps after 10 to 15 days. These deposits later developed into more regular NMJ. The newly formed NMJ were innervated by sprouting axons which penetrated through the connective tissue scar separating the stumps. While denervated, the myofibers of the abjunctional segments underwent marked atrophy, which was reversed when reinnervation had ensued. In conclusion, we demonstrate for the first time that mature myofiber segments devoid of previous NMJ can induce both sprouting from intact axon terminals and formation of new "ectopic" NMJ on their own surface. This type of reinnervation is likely to occur only when myofibers are asymmetrically transected by a trauma. The signaling molecules possibly involved in this phenomenon are discussed. PMID- 7876888 TI - Selective dendritic alterations in the cortex of Rett syndrome. AB - Rett syndrome, the commonest condition associated with severe mental retardation in girls, is diagnosed only by its clinical phenotype, because, to date, there is no consistent characteristic alteration in genetic, biochemical, neurotransmitter or morphologic marker. The clinical features at various ages suggest involvement of most parts of the nervous system, however, the brain in Rett syndrome is reduced in weight, without other obvious morphologic alterations. Because of the relative microcephaly, hypotheses regarding failure of development have been suggested. Supporting such hypotheses are the quantitative studies by Jellinger, Seitelberger and Kitt defining a decrease in the amount of melanin in the substantia nigra and by Bauman defining a global decrease in the size of the neurons. In this study the cerebral cortex has been examined using the rapid Golgi technique with the purpose of investigating dendrites of pyramidal neurons in six cortical regions of Rett girls from ages 2.9-35 years. Camera lucida drawings of apical and basal dendrites of two cortical layers and CA1 were prepared. These were submitted to the Sholl analysis. The Sholl analyses were tested for significance using the repeated measures analysis of covariance, with age as a covariate. The studies demonstrate that from our samples there is no evidence that the pyramidal neurons in Rett syndrome degenerate progressively with increasing age but that the basal dendrites of layers three and five pyramidal neurons in the motor and frontal cortex, the apical dendrites of layer five of the motor cortex, and the basal dendrites of layer four of the subiculum are significantly shorter than in non-Rett brains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876889 TI - Association of Wilms' tumor with primary brain tumor in siblings. AB - The cases of two young male siblings independently developing unilateral Wilms' tumors and brain tumors are reported. The renal tumors were resected; the first child was treated with chemotherapy and the second child was given additional radiotherapy. Five years after treatment, both children developed a second primary neuroectodermal tumor. All four tumors showed a high proliferative activity, and rapidly progressing disease led to the death of the first child. Histopathological and molecular studies were carried out on all four neoplasms. No functionally relevant mutation was found in selected exons of the p53, K-ras and WT1 gene loci of tumor and germ line DNA. Since additional family members had developed brain tumors and carcinomas, this peculiar association of neoplasms may be due to germ line mutation of a hitherto unidentified oncogene acting in a recessive or weakly dominant fashion. PMID- 7876890 TI - Cytogenetic, molecular genetic and pathological analyses in 126 meningiomas. AB - In a series of 126 meningiomas, tumor and patient characteristics were investigated and statistically analyzed. A combined cytogenetic and molecular genetic approach was used to study chromosomal abnormalities and loss of markers on chromosome 22q. This approach was successfully applied to 93 meningiomas. In 66 cases, complete or partial loss of chromosome 22 was observed and in at least 12 of them this chromosome was involved in structural aberrations. In addition to chromosome 22 changes, chromosomes 1, 6, 11, 13, 14, 18, 19, X, and Y were also frequently involved in structural and numerical aberrations. Statistical analysis revealed a significant association between the number of chromosomal abnormalities and tumor grade. Complex karyotypes predominated in the group of grade II/III meningiomas. Furthermore, other variables showed statistically (or marginally statistically) significant differences. Meningiomas from the convexity were more often grade II/III, displayed predominantly (partial) loss of chromosome 22 and had complex karyotypes more often. These features were frequently found in meningiomas from males. Base meningiomas, on the other hand, occurred more often in females; they were usually grade I, showed loss of (parts of) chromosome 22 less often and displayed fewer additional chromosomal abnormalities. PMID- 7876891 TI - Effects of transforming growth factor-beta 1 on collagen synthesis, integrin expression, adhesion and invasion of glioma cells. AB - Transforming growth factor-beta 1 (TGF-beta 1) as a potent modulator of cell extracellular matrix (ECM) interactions may be related to poorly understood ECM associated features of glioblastomas, such as diffuse brain invasion, rarity of extracranial metastasis and marked ECM production in vitro. We therefore studied TGF-beta 1 expression in glioblastoma biopsy specimens and cell lines by using reverse transcription-polymerase chain reaction (RT-PCR). The cell lines were also examined by Western blotting and immunocytochemistry. To determine effects of TGF-beta 1, glioma cell lines U-138MG and U-373MG were incubated for 48 hours with TGF-beta 1 (0.1, 1, 10 ng/ml) or with antisense phosphorothioate oligodeoxynucleotides (APO) designed to specifically inhibit TGF-beta 1 gene expression. Thereafter, collagen synthesis was determined by isotopic labeling with 3H-proline; integrin expression by flow cytometry; adhesion on collagen types I and IV, laminin and fibronectin by adhesion assays; and invasion through reconstituted basement membrane by invasion assays. We found that TGF-beta 1 was expressed by all glioma cell lines at protein and mRNA levels. Pretreatment with TGF-beta 1 increased the amount of collagen synthesis/cell, upregulated the alpha 5 integrin chain of U-138MG cells, and facilitated adhesion on all ECM substrates, while invasion of U-138MG cells, but not that of U-373MG cells, was markedly reduced. Conversely, pretreatment with APO reduced TGF-beta 1 protein expression levels, inhibited adhesion and increased invasion of U-138MG cells, but did not affect collagen synthesis. We conclude that exogenously applied TGF beta 1 exerts marked effects on ECM-related features of glioma cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876892 TI - Glioneuronal malformative lesions and dysembryoplastic neuroepithelial tumors in patients with chronic pharmacoresistant epilepsies. AB - Malformative glioneuronal lesions were examined in surgical specimens from 43 patients with chronic focal epilepsies in order to determine the scope of histopathological changes and to better understand their pathogenesis. The most common lesions were hamartias composed of randomly oriented neurons and astrocytes (24 cases). Most of these lesions also contained clustered oligodendrocyte-like cells which were often strongly immunoreactive for the developmentally regulated embryonal form of the neural cell adhesion molecule (E NCAM). These hamartias were typically minute, multifocal, and arranged in a pattern suggestive of a migration disorder. There were eight cases with aggregates of large disfigured neurons, oversized atypical astrocytes and ballooned multinucleated giant cells reminiscent of tuberous sclerosis-associated changes. Finally, there were 11 dysembryoplastic neuroepithelial tumors (DNT), an entity which has been proposed to be malformative rather than neoplastic. The oligodendroglia-like cells in DNT were negative for E-NCAM. However, strong E NCAM expression was present in many dysplastic neurons of tuberous sclerosis-like lesions, hamartias and DNT and in reactive astrocytes. Significant immunoreactivity for the proliferation associated Ki-67 antigen was not observed. No similar lesions were observed in 500 consecutive autopsies from patients without epilepsy. Malformative glioneuronal lesions appear to be highly epileptogenic and most likely result from a disordered cell migration and differentiation. PMID- 7876893 TI - Excitotoxic cytopathology, progression, and reversibility of thiamine deficiency induced diencephalic lesions. AB - The present study examined the cytopathological changes within diencephalon of a rat model of Wernicke's encephalopathy and determined whether administration of thiamine at various intervals after onset of neurological signs can arrest or reverse the cytopathological process. Electron microscopic examination of the brains from animals sacrificed at four progressively severe stages of pyrithiamine-induced thiamine deficiency (PTD) revealed neurocytopathological changes identical to those that have been described in glutamate-induced excitotoxic lesions. These degenerative changes occurred in gelatinosus (Ge) and anteroventral ventrolateral (AVVL) nuclei at an early symptomatic stage and in the ventroposterolateral (VPL), ventroposteromedial (VPM), and ventrolateral (VL) nuclei at slightly later stages of PTD. Light microscopic evaluation of separate groups of PTD rats administered thiamine at each of the same four neurologic stages and allowed to recover for 1 week demonstrated that thiamine treatment is more effective when administered at earlier stages. However, Ge, AVVL, and VPL nuclei sustain severe damage even when thiamine is administered prior to acute neurologic signs. Furthermore, pathologic changes in the mammillary and several midline intralaminar nuclei begin after thiamine administration and reinstitution of thiamine-replete diet to animals in more severe stages of thiamine deficiency. These and other recent findings suggest that excitotoxic and possibly apoptotic mechanisms may mediate neuronal degeneration in the PTD rat model of Wernicke's encephalopathy, and that multiple factors conducive to excitotoxicity may act in concert to produce this syndrome. PMID- 7876894 TI - Multicystic encephalopathy: review of eight cases with etiologic considerations. AB - Multicystic encephalomalacia (MCE) is a rare lesion that arises during the perinatal period. Although hypoxic-ischemic insults may be responsible for this lesion, recent evidence suggests that herpesviruses may represent another etiologic agent. To elucidate the pathogenesis of MCE, eight cases collected over a 34-year period were evaluated for destructive lesions in gray and white matter. Immunocytochemical methods, in situ hybridization and polymerase chain reaction (PCR) methodology were employed to search for herpes simplex viruses types 1 and 2 (HSV1 and HSV2), cytomegalovirus (CMV), varicella zoster virus (VZV), Epstein Barr virus (EBV) and JC variant of papovavirus (JCV). Review of the clinical histories revealed that there had been a complicated labor and delivery in 6/7 cases. Neuropathological lesions consisted of extensive tissue destruction, neuronal loss and gliosis in hemispheric white matter, cerebral cortex, basal ganglia, thalamus, cerebellum and brainstem tegmentum. Only one case showed evidence of latent HSV infection by PCR. CMV, VZV, JCV and EBV were not detected. Arteriopathy was noted in one case. The widespread nature of the lesions and their association with perinatal ischemia suggest that severe hypoxia may be the more common etiology of MCE. Term infants appear especially susceptible to this type of cerebral damage. PMID- 7876895 TI - Interleukin-1 expression in different plaque types in Alzheimer's disease: significance in plaque evolution. AB - The histologically apparent polymorphism of plaques containing beta-amyloid in Alzheimer's disease is thought to represent different stages in plaque evolution. beta-amyloid-immunopositive plaques were classified according to the pattern of beta-amyloid distribution (diffuse vs dense-core) and the presence or absence of dystrophic beta-amyloid precursor protein-immunopositive (beta-APP+) neurites (neuritic vs non-neuritic). The potential contribution of microglia-derived interleukin-1 (IL-1), an immune response cytokine that induces synthesis and processing of beta-APP, to the possible sequential development of these plaque types was examined through determination of the number of IL-1 alpha+ microglia associated with each of four identified plaque types. Diffuse non-neuritic plaques had the least dense and most widely dispersed beta-amyloid, did not exhibit beta-APP+ dystrophic neurites, but most (78%) contained activated IL-1 alpha+ microglia (2 +/- 0.2/plaque; mean +/- SEM). Diffuse neuritic plaques had more dense, but still widely dispersed beta-amyloid, displayed a profusion of beta-APP+ dystrophic neurites, and had the greatest numbers of associated activated IL-1 alpha+ microglia (7 +/- 0.8/plaque). Dense-core neuritic plaques had both compact and diffuse beta-amyloid and had fewer IL-1 alpha+ microglia (4 +/- 0.4/plaque). Dense-core, non-neuritic plaques had compact beta-amyloid, lacked associated diffuse beta-amyloid, and were devoid of both IL-1 alpha+ microglia and beta-APP+ dystrophic neurites. These results suggest an important immunological component in the evolution of amyloid-containing plaques in Alzheimer's disease and further suggest that IL-1-expressing cells are necessary to initiate dystrophic neurite formation in diffuse beta-amyloid deposits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876896 TI - Rational design of hirulog-type inhibitors of thrombin. AB - The two crystal structures of thrombin complexed with its most potent natural inhibitor hirudin and with the active-site inhibitor D-Phe-Pro-Arg-CH2Cl [Rydel, T.J. et al., J. Mol. Biol., 221 (1991) 583; Bode, W. et al., EMBO J., 8 (1989) 3467] were used as a basis to design a new inhibitor, combining the high specificity of the polypeptide hirudin with the simpler chemistry of an organic compound. In the new inhibitor, the C-terminal amino acid residues 53-65 of hirudin are linked by a spacer peptide of four glycines to the active-site inhibitor NAPAP (N alpha-(2-naphthyl-sulfonyl-glycyl)-DL-p-amidinophenylalanyl piperi dine). Energy minimization techniques served as a tool to determine the preferred configuration at the amidinophenylalanine and the modified piperidine moiety of the inhibitor. The predictions are supported by the interaction energies determined for D- and L-NAPAP in complex with thrombin, which are in good agreement with experimentally determined dissociation constants. The conformational flexibility of the linker peptide in the new inhibitors was investigated with molecular dynamics techniques. A correlation between the Pl' position and the interactions of the linker peptide with the protein is suggested. Modifications of the linker peptide are proposed based on the distribution of its main-chain torsion angles in order to enhance its binding to thrombin. PMID- 7876897 TI - Derivation of a 3D pharmacophore model for the angiotensin-II site one receptor. AB - A systematic search has been used to derive a hypothesis for the receptor-bound conformation of A-II antagonists at the AT1 receptor. The validity of the pharmacophore hypothesis has been tested using CoMFA, which included 50 diverse A II antagonists, spanning four orders of magnitude in activity. The resulting cross-validated R2 of 0.64 (conventional R2 of 0.76) is indicative of a good predictive model of activity, and has been used to estimate potency for a variety of non-peptidyl antagonists. The structural model for the non-peptide has been compared with respect to the natural substrate, A-II, by generating peptide to non-peptide overlays. PMID- 7876898 TI - Electrostatic complementarity between proteins and ligands. 1. Charge disposition, dielectric and interface effects. AB - Electrostatic interactions have always been considered an important factor governing ligand-receptor interactions. Previous work in this field has established the existence of electrostatic complementarity between the ligand and its receptor site. However, this property has not been treated rigorously, and the description remains largely qualitative. In this work, 34 data sets of high quality were chosen from the Brookhaven Protein Databank. The electrostatic complementary has been calculated between the surface potentials; complementarity is absent between adjacent or neighbouring atoms of the ligand and the receptor. There is little difference between complementarities on the total ligand surface and the interfacial region. Altering the homogeneous dielectric to distance dependent dielectrics reduces the complementarity slightly, but does not affect the pattern of complementarity. PMID- 7876899 TI - Electrostatic complementarity between proteins and ligands. 2. Ligand moieties. AB - Drug design strategies consider factors governing intermolecular interactions to build up putative ligands. In many strategies, the ligand is constructed using fragments which are placed in the site sequentially. The optimization is then performed with each fragment. We would like to examine if this optimization strategy could generate ligands with optimal electrostatic interactions. The electrostatic complementarities between constituent moieties and the receptor site have been calculated. The whole-ligand complementarity does not appear to be the mathematical mean of the individual complementarities, nor have we found a simple relationship between the moiety and whole-ligand complementarities. The results demonstrate clearly that, using a simple model, it is very difficult to predict the electrostatic potential complementarity of the whole ligand from the complementarities of its constituent chemical moieties. This means that ligand design strategies must optimize the electrostatic complementarity globally, and not moiety by moiety. PMID- 7876900 TI - Electrostatic complementarity between proteins and ligands. 3. Structural basis. AB - Electrostatic potential complementarity between ligands and their receptor sites is evaluated by the superposition of the electrostatic potential, generated by the receptor, onto the ligand potential over the ligand van der Waals surface. We would like to examine which structural factors generate this pattern of superposition. Example studies suggest that in many ligand-protein pairs, there exist principal formal charges on each molecule, largely responsible for the electrostatic potential complementarity observed. Electrostatic potential complementarity depends on the relative disposition of these principal charges and the ligand van der Waals surface. Simple mathematical models were constructed to predict the complementarity solely from structural considerations. The essential conditions for electrostatic potential complementarity were elucidated. These can be used in ligand design strategies to obtain an electrostatically optimal ligand. PMID- 7876901 TI - Flexibases: a way to enhance the use of molecular docking methods. AB - Specially expanded databases containing three-dimensional structures are created to enhance the utility of docking methods to find new leads, i.e., active compounds of pharmacological interest. The expansion is based on the automatic generation of a set of maximally dissimilar conformations. The ligand receptor system of methotrexate and dihydrofolate reductase is used to demonstrate the feasibility of creating flexibases and their utility in docking studies. PMID- 7876902 TI - A fast and efficient method to generate biologically relevant conformations. AB - Mutual binding between a ligand of low molecular weight and its macromolecular receptor demands structural complementarity of both species at the recognition site. To predict binding properties of new molecules before synthesis, information about possible conformations of drug molecules at the active site is required, especially if the 3D structure of the receptor is not known. The statistical analysis of small-molecule crystal data allows one to elucidate conformational preferences of molecular fragments and accordingly to compile libraries of putative ligand conformations. A comparison of geometries adopted by corresponding fragments in ligands bound to proteins shows similar distributions in conformations space. We have developed an automatic procedure that generates different conformers of a given ligand. The entire molecule is decomposed into its individual ring and open-chain torsional fragments, each used in a variety of favorable conformations. The latter ones are produced according to the library information about conformational preferences. During this building process, an extensive energy ranking is applied. Conformers ranked as energetically favorable are subjected to an optimization in torsion angle space. During minimization, unfavorable van der Waals interactions are removed while keeping the open-chain torsion angles as close as possible to the experimentally most frequently observed values. In order to assess how well the generated conformers map conformation space, a comparison with experimental data has been performed. This comparison gives some confidence in the efficiency and completeness of this approach. For some ligands that had been structurally characterized by protein crystallography the program was used to generate sets of some 10 to 100 conformers. Among these, geometries are found that fall convincingly close to the conformations actually adopted by these ligands at the binding site. PMID- 7876903 TI - An evaluation of molecular models of the cytochrome P450 Streptomyces griseolus enzymes P450SU1 and P450SU2. AB - P450SU1 and P450SU2 are herbicide-inducible bacterial cytochrome P450 enzymes from Streptomyces griseolus. They have two of the highest sequence indentities to camphor hydroxylase (P450cam from Pseudomonas putida), the cytochrome P450 with the first known crystal structure. We have built several models of these two proteins to investigate the variability in the structures that can occur from using different modeling protocols. We looked at variability due to alignment methods, backbone loop conformations and refinement methods. We have constructed two models for each protein using two alignment algorithms, and then an additional model using an identical alignment but different loop conformations for both buried and surface loops. The alignments used to build the models were created using the Needleman-Wunsch method, adapted for multiple sequences, and a manual method that utilized both a dot-matrix search matrix and the Needleman Wunsch method. After constructing the initial models, several energy minimization methods were used to explore the variability in the final models caused by the choice of minimization techniques. Features of cytochrome P450cam and the cytochrome P450 superfamily, such as the ferredoxin binding site, the heme binding site and the substrate binding site were used to evaluate the validity of the models. Although the final structures were very similar between the models with different alignments, active-site residues were found to be dependent on the conformations of buried loops and early stages of energy minimization. We show which regions of the active site are the most dependent on the particular methods used, and which parts of the structures seem to be independent of the methods. PMID- 7876904 TI - On the use of LUDI to search the Fine Chemicals Directory for ligands of proteins of known three-dimensional structure. AB - It is shown that the computer program LUDI can be used to search large database of three-dimensional structures for putative ligands of proteins with known 3D structure. As an example, a subset of approximately 30,000 small molecules (with less than 40 atoms and 0-2 rotatable bonds) from the Fine Chemicals Directory has been used in the search for possible novel ligands for four different proteins (trypsin, streptavidin, purine nucleoside phosphorylase and HIV protease). For trypsin and streptavidin, known ligands or substructures of known ligands are retrieved as top-scoring hits. In addition, a number of new interesting structures are found in all considered cases. Therefore, the method holds promise to retrieve automatically protein ligands from a 3D database if the 3D structure of the target protein is known. PMID- 7876905 TI - Education and practice collaboration: a strategy for curriculum development. AB - Five schools of nursing in British Columbia formed a collaborative partnership in 1989; four represented diploma programs, and one a post-RN program. Their partnership benefited each in the development of a baccalaureate nursing curriculum. Committed to the principle of a curriculum being driven by practice, rather than the reverse, the collaborative partners employed a variety of strategies to include nurses from practice in the development of the curriculum. One strategy used by the partnership was a Delphi survey of nurses in practice. This article describes the results of this survey and their implications for nursing curricula. PMID- 7876906 TI - The relationship between clinical education format and selected student learning outcomes. PMID- 7876907 TI - Attitudes of nurse-faculty toward post-tenure performance evaluations. AB - While non-tenured faculty receive feedback on their work in their annual evaluations for reappointment, many tenured faculty do not receive evaluations and feedback except when seeking merit award or promotion. Recent literature suggests that feedback on work at fixed time intervals, through post-tenure evaluations, can positively enhance faculty productivity. This survey study examined the attitudes of faculty teaching in baccalaureate and higher degree programs in nursing toward post-tenure performance evaluations. A random, nationwide sample of 248 nurse-faculty participated in this study. Data analysis showed that attitude toward post-tenure evaluation was not significantly related to such variables as tenure status, perceived productivity in teaching, service, scholarship, internal motivation, age, teaching experience, sex, educational preparation, or rank. Faculty clearly stated that they desire feedback on their work, an opportunity to define future objectives, and a post-tenure evaluation system in their own schools. PMID- 7876908 TI - JNE's year in review. PMID- 7876909 TI - Education of nursing students with special needs. AB - Recent legislation such as the Americans with Disabilities Act will have a significant impact on higher education in nursing. A survey was conducted to describe the extent to which BSN and ADN nursing programs in the United States admit and graduate special needs and chronically ill students, and to identify the accommodations which have been successful in providing nursing education to these students. Responses received from 86 schools of nursing in 44 states indicated that most schools have had contact with students with special needs such as visual, hearing, or mobility impairments, learning disabilities, and mental or chronic illnesses. Learning disabilities and mental impairment were cited most frequently as having been present among the student population. Few programs have had experience with students with vision problems. While most programs responding had little experience with providing special accommodations to special needs students, most were aware of accessibility on their campuses. Recent legislation aimed at creating opportunities for disabled individuals to successfully enter the work force creates challenges for schools of nursing in education of students with special needs. Issues are raised that must be addressed to meet this important challenge. PMID- 7876910 TI - Selecting clinical learning experiences: an analysis of the factors involved. PMID- 7876911 TI - Ethical problems encountered in the teaching of nursing: student and faculty perceptions. PMID- 7876912 TI - Evaluation of a curriculum for adequacy of AIDS content. PMID- 7876913 TI - The quieting response (QR): a modality for reduction of psychophysiologic stress in nursing students. AB - The purpose of this study was to investigate the effects of a 5-week stress management program for 40 junior baccalaureate nursing students. A quasi experimental pretest-posttest control group design was used. The stress management group included training sessions using cognitive modification techniques and Stroebel's Quieting Response (QR) augmented with biofeedback techniques for self-relaxation. A significant reduction of state anxiety (P < .001) was reported on the State-Trait Anxiety Inventory (STAI) by the experimental groups, while the state anxiety of the control groups remained relatively unchanged. There were no significant changes in trait anxiety scores. Urinary potassium excretion was measured as an index of the adrenal stress response. Findings revealed no statistically significant correlation between potassium excretion and scores on the STAI. These results support the benefits of integrating a stress management program into curricula for nursing students. PMID- 7876914 TI - Activity of cAMP-dependent protein kinase is reduced in protein-energy malnourished rats. AB - Glucagon decreases glutathione synthesis in hepatocytes from well-nourished rats. However, in hepatocytes from malnourished rats, glucagon does not inhibit glutathione synthesis, suggesting a desensitization of cAMP-mediated signal transduction. We investigated the mechanism for this desensitization of cAMP mediated responsiveness in malnourished rats by comparing the signal transduction pathways in rats fed very low protein diets (0.5 g protein/100 g diet) with those of rats fed diets adequate in protein (15 g protein/100 g diet) for 2 wk. Glucagon receptor and forskolin-stimulated cAMP production were greater in hepatocytes from malnourished rats. Stimulation of adenylyl cyclase with forskolin, guanine nucleotides or manganese in hepatic membranes was also enhanced after malnutrition. Moreover, quantity of the stimulatory guanine nucleotide regulatory protein was 70-80% greater in hepatocytes from malnourished rats but the inhibitory guanine nucleotide regulatory protein was not different. These results suggested that desensitization of cAMP-mediated signal transduction after malnutrition occurred at a site distal to cAMP production. Maximal activity of cAMP-dependent protein kinase was 60% lower in liver homogenates from malnourished rats compared with controls. This difference in activity was confined to the cytosolic compartment, with no difference in activity observed in the particulate fraction. Lower activity of cAMP-dependent protein kinase in the cytosol of malnourished rats was associated with a 43% reduction in the quantity of regulatory subunit type I, with no difference in the regulatory subunit type II. These data indicate that desensitization of cAMP signal transduction in rat liver after malnutrition is due to a decrease in the quantity and activity of cAMP-dependent protein kinase. PMID- 7876915 TI - Expression of heat shock genes in hepatocytes is affected by age and food restriction in rats. AB - The objective of this study was to determine how food restriction altered the age related changes in the basal and heat-induced expression of heat shock genes (hsc70, grp78, and ubiquitin) by hepatocytes isolated from young (4 to 6 mo old) and old (26 to 28 mo old) male Fischer 344 rats. The basal levels of the mRNA transcripts for hsc70 and ubiquitin were similar for hepatocytes isolated from young and old rats fed with free access to the diet (control) or from rats fed a restricted diet (40% restriction of food intake). However, the induction of the mRNA transcripts for hsc70 and ubiquitin by a heat shock (42.5 degrees C for 30 min) was significantly higher for hepatocytes isolated from old rats fed the restricted diet compared with old rats fed with free access to the diet. The changes in hsc70 mRNA levels were paralleled by similar changes in hsc70 transcription by isolated nuclei; therefore, the greater induction of hsc70 expression by food restriction results from changes in the transcription of hsc70 gene. In contrast with hsc70 and ubiquitin, the basal levels of grp78 were reduced with age and by food restriction. Therefore, the effect of aging and food restriction on the basal and heat-induced expression of heat shock genes varies considerably from gene to gene. PMID- 7876916 TI - Human milk glycosaminoglycans inhibit HIV glycoprotein gp120 binding to its host cell CD4 receptor. AB - The binding of the HIV envelope glycoprotein, gp120, to its host cell receptor, CD4, is inhibited in a solid phase assay by a glycosaminoglycan of human milk; this binding is the essential first step in HIV infectivity. The human milk glycosaminoglycans were identified in this study. Pooled, fractionated human milk contained dermatan sulfate, heparin, heparan sulfate, and chondroitin sulfate. The ability of this glycosaminoglycan fraction to inhibit binding was unaffected by digestion with lytic enzymes specific for heparin, heparan sulfate and dermatan sulfate, but was lost when the milk fraction was treated with lytic enzymes specific for chondroitin sulfate. Furthermore, a purified milk fraction with high specific inhibitory activity contained chondroitin sulfate but not other glycosaminoglycans. This indicates that the ability of human milk to inhibit gp120 binding to CD4 may be attributed to chondroitin sulfate or to a chondroitin sulfate-like moiety rather than to other components of human milk. We speculate that this human milk glycosaminoglycan could limit the rate of postnatal vertical transmission of HIV in breast-fed infants of HIV-infected mothers. PMID- 7876917 TI - Dietary monounsaturated and polyunsaturated fatty acids are comparable in their effects on hepatic apolipoprotein mRNA abundance and liver lipid concentrations when substituted for saturated fatty acids in cynomolgus monkeys. AB - Although studies have shown that saturated and polyunsaturated fats can mediate plasma lipid and apolipoprotein (apo) concentrations at the mRNA level, there is little data on the role of monounsaturated fats. We determined hepatic lipid and apo mRNA levels in 10 cynomolgus monkeys fed three diets that provided 30% of energy as fat with 0.1% cholesterol by weight and differed solely by the substitution of saturated, mono- and polyunsaturated fats as 60% of total fat energy. Total, LDL, and HDL cholesterol, as well as LDL apo B, HDL apo A-I and HDL total apo C concentrations, were reduced with the mono- and polyunsaturated fat diets relative to the saturated fat diet. Although fat saturation did not significantly affect hepatic apo A-I, B, C-II, or E mRNA abundance, hepatic apo C III mRNA concentrations were uniformly lower (-23%, P < 0.01) with the mono- and polyunsaturated fat diets than with the saturated fat diet. Interestingly, liver triglycerides were significantly elevated with the monounsaturated fat diet relative to the saturated fat diet, but no other differences in hepatic lipids were noted among diets. Hepatic triglyceride composition was shown to reflect dietary fatty acid composition, with liver triglycerides enriched in myristic and palmitic fatty acids during the saturated fat diet, oleic acid during the monounsaturated fat diet and linoleic acid during the polyunsaturated fat diet. We conclude that dietary monounsaturated fats are comparable to polyunsaturated fats in their effects on hepatic lipid and apo mRNA levels in this species, with both unsaturated fats significantly reducing only hepatic apo C-III mRNA abundance relative to saturated fat. PMID- 7876918 TI - Dietary soybean may be antiestrogenic in male mice. AB - We tested whether dietary soybeans alter prostatic growth and development of prostatic dysplasia in mice that were treated with a synthetic nonsteroidal estrogen, diethylstilbestrol during the first 3 d after birth. Soybeans were chosen because they contain substantial amounts of isoflavonic estrogens. The presence of estrogenic isoflavonoids in soybean-containing feed was confirmed by measuring the excretion of seven different plant estrogens in the urine of normal adult male mice. Estrogenicity of dietary soybean was confirmed by the growth response in uteruses of immature mice. In addition to their estrogenic effect, antiestrogenic properties of soybeans on uterine growth were observed in the presence of a more potent estrogenic growth stimulator, diethylstilbestrol in feed. In neonatally estrogenized male mice, soybean feeding reduced the prostatic growth inhibition due to diethylstilbestrol and, in preliminary experiments, delayed the development of dysplastic changes in the prostate. The number of animals showing severe dysplasia in prostatic epithelium was significantly lower in 9-mo-old animals given soybean-containing feed from fertilization onwards, but in 12 mo-old animals the difference was less obvious and was not significant. Our findings suggest an antiestrogenic action for dietary soybean in male mice, which may be important for the hormonal regulation of normal as well as neoplastic prostatic growth. PMID- 7876919 TI - Uptake of dietary coenzyme Q supplement is limited in rats. AB - Coenzyme Q is an important mitochondrial redox component and the only endogenously produced lipid-soluble antioxidant. Its tissue concentration decreases with aging and in a number of diseases; dietary supplementation of this lipid would fulfill important functions by counteracting coenzyme Q depletion. To investigate possible uptake, rats were administered 12 mumol coenzyme Q10/100 g body wt once daily by gastric intubation. The appearance of coenzyme Q10 in various tissues and blood after 6 h, 4 d or 8 d was studied. The control group of rats received rapeseed-soybean oil (the vehicle in the experimental group). Lipids were extracted with petroleum ethermethanol, and the reduced and oxidized forms of coenzyme Q9 and Q10 were separated and quantified by reversed-phase HPLC. In the plasma, the total coenzyme Q concentration was doubled after 4 d of treatment. Coenzyme Q10 was also recovered in liver homogenates, where, as in the plasma, it was largely in the reduced form. Uptake into the spleen could be to a large extent accounted for by the blood content of this organ. No dietary coenzyme Q10 was recovered in the heart or kidney. The uptake in the whole body was 2-3% of the total dose. Coenzyme Q10 found in the liver was located mainly in the lysosomes. Dietary coenzyme Q10 did not influence the endogenous biosynthesis of coenzyme Q9. This is in contrast to dietary cholesterol, which down-regulates cholesterol biosynthesis. The dietary coenzyme Q10 level in the plasma decreased to approximately 50% after 4 d. These results suggest that dietary coenzyme Q10 may play a role primarily in the blood and that no appreciable uptake occurs into tissues. PMID- 7876920 TI - Cholesterol 7 alpha-hydroxylase activity is increased by dietary modification with psyllium hydrocolloid, pectin, cholesterol and cholestyramine in rats. AB - Sources of dietary fiber known to alter cholesterol metabolism and/or bile acid pool size were fed to rats, and activity of the rate-limiting step in bile acid synthesis, cholesterol 7 alpha-hydroxylase, was measured. In the first experiment, semipurified diets containing 5% cellulose, psyllium hydrocolloid, pectin or oat bran as dietary fiber sources or 2% cholestyramine were fed to groups of 10 male Wistar rats for 4 wk. In the second experiment, groups of six rats were fed diets containing 5% cellulose, rice bran, oat bran or psyllium with and without 0.25% cholesterol. In the first experiment, the activity of cholesterol 7 alpha-hydroxylase (pmol.min-1.mg protein-1) was highest in the cholestyramine-treated group (95.6 +/- 3.6), followed by groups fed psyllium (35.5 +/- 3.5) or pectin (36.0 +/- 4.5), which exhibited more than twice the enzyme activity of groups fed cellulose (16.9 +/- 1.9) or oat bran (12.3 +/- 2.0). In the second experiment, feeding cholesterol resulted in significantly higher enzyme activity when cellulose (65%), oat bran (118%) and rice bran (60%) were fed, but no difference in activity was observed when cholesterol was added to the psyllium-containing diet. Higher activity of cholesterol 7 alpha hydroxylase when pectin or psyllium rather than cellulose was fed may explain the almost twofold higher bile acid pool sizes previously reported in response to feeding either of these fibers. These data support the hypothesis that the hypocholesterolemic effect of soluble fibers is modulated through increased synthesis and therefore pool size of bile acids. PMID- 7876921 TI - Arepas made from high amylose corn flour produce favorably low glucose and insulin responses in healthy humans. AB - The importance of the amylose: amylopectin ratio in the postprandial glycemic and insulinemic responses to corn was studied in food products that might realistically be consumed. Healthy subjects were given test meals in the form of arepas made from ordinary (25% amylose) or high amylose (70% amylose) corn flour. The ordinary corn meal contained 45 g of potentially available starch. To exclude the possible influence of a lowered content of potentially available starch due to formation of resistant starch in the high amylose product, this product was evaluated at two levels and included either on the basis of potentially available starch (45 g) or total starch (including resistant starch) (45 g, i.e., 29 g potentially available starch), respectively. The rate of starch hydrolysis, measured in vitro employing a method based on chewing, was studied. In addition, the content of in vitro resistant starch was analyzed in all products. The meals containing high amylose corn flour produced lower areas under the glucose and insulin response curves (57 and 42% lower, respectively) than did the meals containing ordinary cornmeal. This could not be explained by a lower amount of potentially available starch. No differences were noted when subjects consumed the two high amylose meals of arepas, despite 36% lower potentially available starch in one of the meals. The rate of starch hydrolysis measured in vitro was slower in the high amylose corn products than in the ordinary corn product. Resistant starch in the ordinary product was 3 g/100 g dry matter, vs. approximately 20 g/100 g dry matter in the high amylose products. We concluded that high amylose corn products have a potential to promote favorably low metabolic responses and high resistant starch contents. PMID- 7876922 TI - Lauric and palmitic acid-enriched diets have minimal impact on serum lipid and lipoprotein concentrations and glucose metabolism in healthy young women. AB - Fifteen healthy young women were fed diets enriched to 4% of energy with either palmitic acid (as palm oil) or lauric acid (as coconut oil). A randomized crossover study design was used so that subjects followed the two experimental diets for 4 wk, both preceded by consumption of a baseline diet for 2 wk. The experimental diets differed only with respect to the fatty acid composition: there was a substitution of 4% of energy intake with palmitic acid or lauric acid in the experimental diets for 4% of energy as monoenes in the baseline diet. There were no differences in the concentration of serum total or lipoprotein lipids, apolipoproteins A-I and B, and lipoprotein (a) or plasma cholesteryl ester transfer protein activity between the experimental diet periods. The VLDL cholesterol concentration (0.38 +/- 0.05 vs. 0.51 +/- 0.05 mmol/L, means +/- SEM, P = 0.01] and plasma cholesteryl ester transfer protein activity [78 +/- 5 vs. 88 +/- 6 mumol/(h.L), P = 0.007) were greater at the end of the lauric acid diet period than at the end of the preceding baseline diet period. No differences were found in glucose effectiveness, insulin sensitivity index or insulin secretion measured by the intravenous glucose tolerance test (Minimal Model method). In conclusion, in terms of serum lipids, lipoproteins, and glucose metabolism, palmitic acid was equal to lauric acid at 4% of total energy intake exchange, and both of these saturated fatty acids were comparable to a 4% of total energy intake exchange with monoenes in healthy young women. PMID- 7876923 TI - Iron status alters murine systemic lupus erythematosus. AB - The effect of Fe status on murine systemic lupus erythematosus was investigated. Weanling female MRL/MPJ-lpr/lpr mice (systemic lupus erythematosus strain) were fed diets with the following levels (mg Fe/kg diet): 3 (severely deficient), 10 (moderately deficient), 35 (control) and 250 (supplemented). A fifth group was pair fed the control diet in the amounts consumed by the severely deficient group. C3H/Hej mice fed the same diets were used as non-lupus controls. Anemia was more severe in severely deficient mice than in all other MRL groups and C3H severely deficient mice. Incidence of skin lesions was highest in MRL severely and moderately deficient mice compared with pair-fed, control and supplemented mice. By 22 wk of age, mortality was higher in supplemented and severely deficient mice than in moderately deficient, pair-fed and control MRL mice. Anti dsDNA activity in serum was not altered by Fe. In a second experiment, kidney function was examined in mice fed severely deficient, control, supplemented and pair-fed diets. Urine protein concentration was highest in supplemented mice at 14 wk of age. Serum urea nitrogen was significantly higher in MRL severely deficient mice than in pair-fed and control mice at 18 wk of age. Glomerular filtration rate, measured by creatinine clearance, was significantly lower in MRL severely deficient mice than in pair-fed and Fe supplemented mice at 16 wk of age and pair-fed and control mice at 18 wk of age. Renal histopathology was more severe in Fe supplemented mice than in pair-fed and control mice, and more severe in severely deficient and pair-fed mice than in control mice. Fluorescent staining of kidneys with anti-Ig G and anti-C3 fluorescein-conjugated antibodies was most intense in severely deficient mice, and the concentration of circulating immune complexes in serum was significantly higher in severely deficient mice than in all other groups. These data demonstrate that systemic lupus erythematosus in MRL/MPJ-lpr/lpr mice is altered by dietary iron. PMID- 7876924 TI - Non-starch polysaccharide-degrading enzymes increase the performance of broiler chickens fed wheat of low apparent metabolizable energy. AB - The effect of a commercial glycanase product (Avizyme TX) on the performance of 4 wk-old broiler chickens fed wheats with low and normal apparent metabolizable energy values was studied. Controls were fed a corn-based diet. Supplementation with the enzyme product significantly (P < 0.01) increased the apparent metabolizable energy of the low metabolizable energy wheat from 12.02 to 14.94 MJ/kg dry matter. The apparent metabolizable energy value of the normal wheat was increased from 14.52 to 14.83 MJ/kg dry matter; this was, however, not significant. Birds fed the low metabolizable energy wheat diet had significantly (P < 0.01) higher digesta viscosity and lower small intestinal starch and protein digestibilities than birds fed the normal wheat diet. Chickens fed the low metabolizable energy wheat tended to grow less than those fed the normal wheat diet. When the low metabolizable energy wheat+enzyme diet was fed, digesta viscosity was significantly (P < 0.01) lower (20.28 vs. 10.36 mPa.s), and small intestinal digestibility coefficient of starch was significantly (P < 0.01) greater (0.584 vs. 0.861) relative to values in birds fed the low metabolizable energy wheat diet alone. Although the protein digestibility coefficient also increased from 0.689 to 0.745, the difference was not significant. Weight gain and feed efficiency of birds fed the low metabolizable energy wheat+enzyme equaled those of controls. The enzyme product significantly (P < 0.01) increased the solubilization of non-starch polysaccharides within the gastrointestinal tract of birds fed both types of wheat diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876925 TI - Consumption of a glucose diet enhances the sensitivity of pancreatic islets from adrenalectomized genetically obese (ob/ob) mice to glucose-induced insulin secretion. AB - Consumption of a glucose diet for 4 d markedly elevates plasma insulin concentrations in adrenalectomized ob/ob mice. The present study examined regulation of insulin secretion from perifused pancreatic islets of female adrenalectomized genetically obese (ob/ob) and lean mice fed a glucose diet for 4 d. These mice were fed a high carbohydrate commercial diet for 21 d, or the high carbohydrate commercial diet for 17 d and a purified high glucose diet for the last 4 d of the 21-d feeding period. Adrenalectomy equalized plasma insulin concentrations, pancreatic islet size, rates of insulin secretion in response to 20 mmol/L glucose and insulin mRNA relative abundance in ob/ob and lean mice fed the commercial diet, but the threshold for glucose-induced insulin secretion determined by a linear glucose gradient remained lower in islets from adrenalectomized ob/ob mice than in those from lean mice (3.8 +/- 0.1 vs. 4.9 +/- 0.2 mmol/L glucose), and addition of acetylcholine to the perifusate lowered the threshold to only 2.0 +/- 0.1 mmol/L glucose in islets from ob/ob mice vs. 3.3 +/ 0.1 mmol/L glucose in lean mice. Switching from the commercial diet to the glucose diet for 4 d increased plasma insulin concentrations -10-fold in islets from adrenalectomized ob/ob mice without affecting islet size, 20 mmol/L glucose induced insulin secretion or insulin mRNA abundance. Consumption of the glucose diet did, however, markedly lower the threshold for glucose-induced insulin secretion in islets from adrenalectomized ob/ob mice to approximate the abnormally low glucose thresholds in intact ob/ob mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876926 TI - Albumin synthesis rates measured with [2H5ring]phenylalanine are not responsive to short-term intravenous nutrients in healthy humans. AB - The response of albumin synthesis rates to infusion of either an intravenous nutrient mixture containing adequate nitrogen and energy or an isotonic saline infusion was compared in adult men. In a crossover study, nine healthy male subjects received a short-term (13.5-h) infusion of either the nutrient mixture or the saline solution, and albumin synthesis rates were measured by a stable isotope technique employing [2H5ring]phenylalanine. Fractional rates of albumin synthesis did not differ significantly between treatments (saline, 7.3 +/- 1.0%/d; intravenous nutrients, 7.8 +/- 1.0%/d). The secretion time of albumin was significantly lower with intravenous nutrients infusion than with saline infusion. Plasma albumin concentration as well as prealbumin and transferrin concentrations decreased over time when subjects were infused with either saline or the nutrient solution as a result of dilution rather than a change in synthesis. These results suggest that albumin synthesis rate does not respond to short-term intravenous nutrients. PMID- 7876927 TI - Tissue protein turnover is altered during catch-up growth following Escherichia coli infection in weanling rats. AB - Infection in young growing animals is manifested by poor tissue protein accretion; during subsequent catch-up growth this is reversed. To account for these changes, protein synthesis and degradation were measured in vivo in skeletal muscle, skin, liver and small intestine in weanling rats during catch-up growth after Escherichia coli infection. Observations were made at d 4, 6, 8, 11 and 14, when infected rats had elevated nitrogen balance. Liver protein mass and turnover were not affected by treatment. Although protein mass of small intestine fell during infection, catch-up was achieved before d 4, suggesting a high priority for protein repletion in this tissue. On d 4, protein mass was lower (P < 0.05) in muscle (-19%) and skin (-23%) in infected vs. control rats. Thereafter growth rates of skeletal muscle and skin were higher (P < 0.001) in infected rats compared with controls. Catch-up growth was most pronounced early, but continued throughout the study. During catch-up growth, protein synthesis (mg/d) in muscle and skin was not different between control and infected animals. Protein synthesis was maintained in muscle because RNA mass was maintained. During catch up growth in muscle and skin of infected rats, there was lower protein degradation (mg/d) than in controls (P < 0.05). We conclude that alterations in protein turnover during catch-up growth are tissue and time dependent and are different from those described in other hyperanabolic states. PMID- 7876928 TI - Swimming endurance capacity of mice is increased by chronic consumption of medium chain triglycerides. AB - The effect of chronic administration of medium-chain triglycerides (MCT) on swimming endurance (swim capacity) was investigated in male Std ddY mice. The mice were fed a diet containing 80 g MCT + 20 g long-chain triglycerides (LCT)/kg diet for 6 wk; mice fed diet containing 100 g LCT/kg diet were used as controls. After being accustomed to swimming, the mice were subjected to forced swimming every 2 d in the current water pool that we had developed, and the total swimming period until exhaustion was measured. The total swimming period was used as the index of swim capacity. The group fed MCT showed significantly greater swim capacity than the control group (89.5 +/- 2.5 vs. 80.2 +/- 2.0 min). In another experiment, after 4 wk of MCT diet consumption, significantly greater swim capacity was found in untrained mice. The major metabolic consequences of the adaptations of muscle to prolonged MCT administration during endurance training were higher activities of 3-oxo acid CoA-transferase (P < 0.01), citrate synthase (P < 0.1) and malate dehydrogenase (P < 0.1). These findings suggest that increases in the enzyme activities of the tricarboxylic acid cycle and ketone body utilization associated with the chronic administration of an MCT-containing diet enhance swim capacity in mice. PMID- 7876929 TI - A single intracerebroventricular injection of dexamethasone elevates food intake and plasma insulin and depresses metabolic rates in adrenalectomized obese (ob/ob) mice. AB - A single intracerebroventricular (ICV) injection of dexamethasone rapidly (within 30 min to 3 h) increases plasma insulin and suppresses oxygen consumption in adrenalectomized ob/ob mice with minimal effects in lean mice. Food intake of these adrenalectomized ob/ob mice was unaffected by ICV dexamethasone during these short-term studies. However, in a longer-term study with adrenalectomized gold thioglucose-lesioned obese mice, food intake increased fourfold 6-8 d after a single ICV injection of dexamethasone. We have now further examined the time course of dexamethasone actions in adrenalectomized ob/ob and lean mice in the 96 h post-injection period. A single ICV injection of dexamethasone increased food intake 32% and plasma insulin 81%, and depressed oxygen consumption 11%, in adrenalectomized ob/ob mice during the 24-h period after injection, without increasing food intake or plasma insulin in lean mice. Oxygen consumption was 14% lower in lean mice 24 and 48 h after dexamethasone injection relative to saline injected lean mice. Food intake and oxygen consumption in ob/ob mice returned to levels in saline-injected controls at 48 and 72 h after injection, respectively. Oxygen consumption of lean mice also returned to control levels at 72 h post injection. Plasma insulin concentrations were similar in dexamethasone- and saline-treated ob/ob and lean mice at 96 h post-injection (the only time point examined other than 24 h). A single ICV injection of dexamethasone exerts both rapid (within 30 min to 3 h) and sustained (days) metabolic actions in ob/ob mice. PMID- 7876930 TI - Ration size and protein intake affect circulating growth hormone concentration, hepatic growth hormone binding and plasma insulin-like growth factor-I immunoreactivity in a marine teleost, the gilthead sea bream (Sparus aurata). AB - The nutritional regulation of the growth hormone liver axis has been studied in gilthead sea bream (Sparus aurata). In a first study, fingerling fish were fed three experimental diets with varying proportions of protein (34, 45 and 55%). A 60% decrease in plasma growth hormone concentration was observed with the increase of specific growth rates and dietary protein levels. An opposite response was observed in hepatic growth hormone-binding sites and plasma insulin like growth factor-I immunoreactivity that would reflect the insensitivity of liver to growth hormone action during relatively low protein intake. In a second study, fish were fed a commercial diet (55% protein) at different feeding levels (0, 1.2, 2.7 and 5.5 g/(100 g body wt.d). An 84% decrease in plasma growth hormone concentration was observed with the increase of specific growth rates and feeding levels from 0 to 2.7 g/(100 g body wt.d). However, significantly greater growth hormone concentration was found in fish fed 5.5 g/(100 g body wt.d) when compared with fish fed 2.7 g/(100 g body wt.d). Hepatic growth hormone-binding sites and plasma insulin-like growth factor-I immunoreactivity increased with the increase of feeding levels from 0 to 2.7 g/(100 g body wt.d), but these values were lower in fish-fed 5.5 g/(100 g body wt.d) than in those fed 2.7 g/(100 g body wt.d). The physiological importance of these results remains to be clarified, though probably it is a part of the mechanism that diminishes feed utilization for growth at high feeding levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876931 TI - Very long-chain fatty acids change the ethanol tolerance of Drosophila melanogaster larvae. AB - This research tested the hypothesis that long-chain saturated fatty acids increase the order of cell membranes of an organism and minimize the detrimental fluidizing effects of ethanol. Unsaturated fatty acids increase membrane fluidity and are unlikely to increase the ethanol tolerance of the organism. Both a fatty acid-free medium and media supplemented with very long-chain fatty acids (20 or more carbons) were fed to wild-type larvae of Drosophila melanogaster; larvae were then transferred to media with or without ethanol to test for effects of the fatty acids on ethanol tolerance. Ethanol decreased the percent of larvae to pupate, and lengthened larval development time. However, the percentage of pupae to reach the adult stage and the weight of adult males increased when the larvae were fed ethanol. The very long-chain, unsaturated fatty acids, arachidonic acid [20:4(n-6)] and docosatetraenoic acid [22:4(n-6)], were associated with increased larval mortality when administered in a medium supplemented with ethanol. Arachidic acid (20:0) increased the percentage of larvae to pupate under ethanol stress, decreased the development time and increased the adult weight in the presence and absence of ethanol. Behenic acid (22:0) was not effectively incorporated into phospholipids and had little effect on growth traits. Thus, the experimental results were consistent with the hypothesis. PMID- 7876932 TI - We have met the enemy and it is us! PMID- 7876933 TI - Guidelines for management of shoulder dystocia. AB - Shoulder dystocia is an unpredictable obstetric emergency that occurs in approximately 0.5% of all vaginal deliveries. It appears to result from size discrepancy between the shoulder girdle and the maternal pelvis, abnormal labor mechanics, or both. Many maneuvers have been suggested to free the impacted anterior shoulder, but no specific maneuver or sequence of manipulations has been proved superior. This represents a difficult clinical problem for the obstetrician because it occurs without warning and can result in serious consequences for the infant and increased morbidity in the parturient. This report offers a descriptive review of the various maneuvers that can be used to resolve shoulder dystocia and outlines a suggested sequence that has been successful for these manipulations. PMID- 7876934 TI - Paternal involvement after perinatal death. AB - This study describes paternal involvement after perinatal death in a large, mostly minority, lower socioeconomic status sample. Paternal presence at birth, holding the baby, and presence at a follow-up appointment were the indicators of paternal involvement. Perinatal death was defined as miscarriage, stillbirth, or neonatal death within 12 hours of birth. Data were collected from a retrospective chart review under the auspices of the Perinatal Mortality Counseling Program at Shands Hospital at the University of Florida, a tertiary care referral center in north central Florida. The sample included 722 cases of perinatal death between July 1978 and April 1991. The results indicated that many fathers experienced perinatal grief. More than half attended the birth, a quarter chose to hold their baby, and one fifth returned with the mother to follow-up appointments. Paternal maternal cohabitation was the variable most predictive of the fathers' involvement after perinatal death. Race was predictive of the father being present at birth and at the follow-up visit, with white fathers more likely to be present than black fathers. Married fathers and those employed in a professional or manual labor occupation were more likely to be present at the birth than fathers who were unemployed, students, incarcerated, or in the military. Gestational age was predictive of the father holding the baby, with the likelihood increasing 1.04 times for each week of increase in gestational age. This study supports the need to include fathers in grief counseling, and the further investigation of the involvement of fathers when a perinatal death occurs. PMID- 7876935 TI - Sepsis in asymptomatic term newborns delivered of antibiotic-treated mothers. AB - This study was undertaken to assess the incidence of culture-proved sepsis in term infants without symptoms born to mothers receiving intrapartum antibiotics and to determine the usefulness of the immature neutrophil: total neutrophil (I:T) ratio in the initial evaluation of these infants. A retrospective chart review was made of 103 infants born during a 3-year period. There was one positive blood culture and two positive cerebrospinal fluid cultures in three different patients; all three isolates were considered contaminants and all patients remained without symptoms. In spite of the lack of culture-proved sepsis and clinical illness, more than 50% of the initial I:T ratios were greater than the usually accepted upper limit of normal (that is, 0.16). We conclude that the incidence of sepsis in this population is very low and the initial I:T ratio is not useful as a predictive tool in term newborns without symptoms. PMID- 7876936 TI - Focal intestinal perforation in the extremely-low-birth-weight infant. AB - The purposes of this report were to (1) document the clinical and laboratory features of 11 extremely-low-birth-weight (ELBW) infants with focal intestinal perforation and (2) investigate the clinical events possibly associated with these perforations by examining matched pairs of infants with and without focal intestinal perforation. During the study period 173 infants with birth weights between 600 and 1000 gm were admitted to the neonatal intensive care nursery. Eleven of these ELBW infants had focal intestinal perforations and formed the study group. These infants were matched with 11 ELBW infants who did not have intestinal perforations or signs of inflammatory bowel disease. The matched pairs were similar in all respects except for a significantly higher percent increase in blood urea nitrogen level after treatment with indomethacin (Wilcoxon signed rank test, p < 0.02) in infants with intestinal perforation. At laparotomy the perforations were noted to be focal, often multiple, and on the antimesenteric border of the distal ileum. None of the infants showed clinical, radiographic, or intraoperative findings that were consistent with classifications for necrotizing enterocolitis (NEC). The incidence of focal intestinal perforation in ELBW infants was 6% versus 2% for typical NEC. In addition, four of the 11 infants with intestinal perforation had positive cultures for either Staphylococcus epidermidis or Candida albicans, whereas none of the infants without perforation had positive cultures during the study period (Fisher's exact test, p < 0.09). We conclude that the clinical presentation and the characteristic intestinal lesions in this group of ELBW infants are distinct from those in typical cases of NEC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876937 TI - Growth patterns for infants weighing less than 801 grams at birth to 3 years of age. AB - Anthropometric measurements of infants weighing < 801 gm were monitored to evaluate growth patterns from birth to 36 months chronologic age, using both standard growth percentiles and Z score descriptors. Mean gestational age was 25.8 weeks, and birth weight was 708.4 gm. The infants had growth delay at hospital discharge with some catch-up growth occurring in the first year. Discrete changes in body growth using the Z score as a descriptor showed movement from a negative SD at 12 months toward the reference mean of zero at 36 months. However, mean length remained < 5th percentile, and mean weight was at approximately the 10th percentile for chronologic age. At 36 months 45% of infants had a head circumference smaller than the 5th percentile for chronologic age. Birth weight < 701 gm was a significant predictor of smaller occipital frontal circumference at 3 years (p = 0.03). Interruption of intrauterine growth after extremely premature birth appears to have long-term effects on growth outcome much like prenatal growth retardation. PMID- 7876938 TI - Clinical characteristics and outcomes of infants requiring long-term neonatal intensive care. AB - This study seeks to better describe the characteristics and outcomes of infants who stay for prolonged periods in the neonatal intensive care unit (NICU). Of 1174 consecutive admissions to a NICU, 73 (6%) met criteria for long-term neonatal intensive care (LTNIC). NICU care totaled 24,631 days; LTNIC infants needed 9152 days (37%). Average NICU stay for LTNIC infants was 125 days (SD +/- 102 days), compared with 14 days +/- 17 days for non-LTNIC infants. The LTNIC infants < or = 1500 gm accounted for 22% of the NICU days of care. There were no differences in gestational age, birth weight, gender, or race between LTNIC and non-LTNIC infants. Survival at discharge was not different, although when neonatal deaths (< or = 28 days) were excluded, the survival of LTNIC infants was significantly less (p < 0.0001). Of 56 LTNIC infants who survived to NICU discharge, 11 (three < or = 1500 gm) subsequently died before 2 years of age, and 10 (six < or = 1500 gm) were probably developmentally delayed. Infants with the longest NICU stays often have multiple medical and surgical problems and unfavorable outcomes, and they consume a disproportionately large percentage of NICU resources. Efforts to contain NICU costs, increase NICU bed availability, and improve NICU outcomes should not ignore infants who require prolonged NICU stays. PMID- 7876939 TI - Health-care professionals' attitudes toward the current level and need for developmental services in neonatal intensive care units. AB - For this descriptive study a survey was constructed to determine neonatal intensive care unit (NICU) health-care staff's perceptions of the present level of and need for developmental services in NICUs. In 14 level III NICUs throughout the state of Illinois, 530 multidisciplinary team members responded. NICU staff described the current and ideal roles of the developmental specialist (DS) in their NICU. In addition, using a 5-point scale, the staff rated six categories of 46 specific developmental protocols that might be incorporated into their current daily care routine. These categories included individualized supportive care, direct caregiving procedures, parent participation, environmental modification, stimulation, and positioning. Then the value of these same protocols in an ideal NICU program were rated. The results indicate that 86% of the staff perceive a need for a DS. Within each of the six categories significantly more developmental interventions were rated ideal, compared with the number of such interventions currently practiced. Individualized supportive care was rated as the most important category, and stimulation was rated as the least useful. Overall, neonatal health care professionals support the implementation of developmental services in the NICU. PMID- 7876940 TI - Streptococcus mitis infection in newborns. AB - Although neonatal infections caused by Streptococcus viridans have been suggested to be less severe than those caused by classic neonatal pathogens, little is known about neonatal infections caused by specific species within this group of bacteria. We report six infants who had S. mitis isolated from blood culture. All were infected at < or = 3 days of age; five of the mothers had perinatal risk factors for neonatal sepsis. Five infants were preterm and three had birth weights < or = 2500 gm. Hematologic abnormalities were common. Two died as a result of the infection. Antibiotic susceptibility testing of four isolates revealed resistance to penicillin and ampicillin in three and resistance to gentamicin in two. In vivo resistance was not observed. S. mitis is not part of normal skin flora, should not be assumed to be a contaminant, and can cause severe neonatal disease. If S. mitis or S. viridans are recovered from a normally sterile body site and the patient fails to improve with penicillin therapy, it seems prudent to switch to vancomycin until susceptibility results are available. PMID- 7876941 TI - Thigh circumference and thigh-to-head ratio in preterm and term infants. AB - The diagnosis of altered fetal growth requires multiple criteria that include not only weight and length measurements, but also head, abdominal, and thigh circumference measurements. This cross-sectional study presents the normal standards for thigh circumference, thigh-to-head ratio, and Rohrer's ponderal index in newborn infants from 27 to 41 weeks' gestation, in relation to gestational age and birth weight. A thigh-to-head ratio of < 0.38 and a ponderal index < 2.3 in a term infant are important measurements for appropriate diagnosis of impaired fetal growth. These standards may also serve as reference for comparison with fetal ultrasonographic measurements. PMID- 7876942 TI - A neonatal case of hydranencephaly caused by atheromatous plaque obstruction of aortic arch: possible association with a congenital cytomegalovirus infection? AB - A neonate was seen with hydranencephaly and aortic arch obstruction possibly caused by congenital cytomegalovirus infection. At autopsy the aortic arch was occluded by atheromatous plaque between the right brachiocephalic artery and left common carotid artery. Congenital cytomegalovirus infection may have caused cardiovascular disease and hydranencephaly in this case. PMID- 7876943 TI - Congenital chest wall mesenchymal hamartoma. AB - The case of an infant with mesenchymal hamartoma of the chest wall is presented, and the role of conservative diagnostic and therapeutic intervention is emphasized. A large mass that involved the right hemithorax and chest wall was detected in utero on routine ultrasonographic studies and diagnosed as mesenchymal hamartoma by percutaneous fine needle biopsy at 4 days after birth. The mass did not enlarge after birth, but surgical debulking was necessary at 1 month because of progressive respiratory compromise. Tumor regrowth was noted over the ensuing 8 months, and a second debulking at 9 months has been followed by a 6-year interval without evidence of recurrence. PMID- 7876944 TI - Special imaging casebook. Neonatal sacrococcygeal teratoma. PMID- 7876945 TI - Ventilatory management casebook. Bronchopulmonary dysplasias. Response to pressure support ventilation. PMID- 7876946 TI - Surprise--it is not reform; it is not reregulation; it is politics as usual. PMID- 7876947 TI - Correlates of major complications and mortality in patients presenting to the emergency department with chest pain and more than bibasilar rales. AB - OBJECTIVE: To identify correlates of major complications and mortality in patients presenting to the emergency department with chest pain and more than bibasilar rales. DESIGN: Prospective cohort study. SETTING: The emergency departments of three university and four community hospitals. PATIENTS: Five hundred patients more than 30 years of age presenting to the emergency departments between 1984 and 1985 with a chief complaint of chest pain not explained by obvious trauma or chest x-ray abnormalities, and more than bibasilar rales on physical examination. MEASUREMENTS AND MAIN RESULTS: A standard data form was used to collect the history, physical examination, vital sign, and electrocardiographic findings. Chart review was carried out to record complications and mortality. One hundred eleven (22%) of the patients had a major complication (ventricular fibrillation, Mobitz II heart block, complete heart block, atrioventricular dissociation, cardiogenic shock, cardiac arrest, endotracheal intubation, intra-aortic balloon pump) or died, 160 (32%) were diagnosed as having myocardial infarction, and 58 (12%) died. Of those patients who had major complications or who died, the first complication occurred within six hours of hospital admission for 32% of the patients and within 24 hours for 47% of the patients. Univariate correlates (p < 0.10) of a major complication or death were entered into a stepwise logistic regression model. In the multivariate model, ST elevation or Q waves not known to be old [adjusted odds ratio (OR) 5.8, 95% confidence interval (CI) 3.0-11.1], ST-T changes of ischemia not known to be old (OR 2.6, 95% CI 1.5-4.6), systolic blood pressure < or = 120 mm Hg (OR 3.2, 95% CI 1.9-5.6), and age > 70 years (OR 1.8, 95% CI 1.1-3.0) were correlates of a major complication or death. CONCLUSION: For patients presenting to the emergency department with chest pain and more than bibasilar rales, major electrocardiographic changes, systolic blood pressure < or = 120 mm Hg, and age > 70 years were correlated with a higher risk of a major complication or death. PMID- 7876948 TI - Electrocardiographic left ventricular hypertrophy in patients with suspected acute cardiac ischemia--its influence on diagnosis, triage, and short-term prognosis: a multicenter study. AB - OBJECTIVE: To understand the diagnostic and short-term prognostic significance of electrocardiographic left ventricular hypertrophy (ECG-LVH) for patients who present to the emergency department with symptoms suggesting acute cardiac ischemia, defined as new or unstable angina pectoris or acute myocardial infarction. DESIGN: Subgroup analysis of a multicenter, prospective study of coronary care unit admitting practices in the prethrombolytic era. SETTING: The emergency departments of six New England hospitals: two urban medical school teaching hospitals, two medical school-affiliated community hospitals in smaller cities, and two rural non-teaching teaching hospitals. PATIENTS: 5,768 patients presenting with symptoms suggesting possible acute cardiac ischemia, including 413 patients who had ECG-LVH defined by the Romhilt-Estes point score criteria and 5,355 patients who had other electrocardiogram (ECG) findings. MAIN RESULTS: Only 26% of the 413 patients who had ECG-LVH were ultimately judged to have had acute cardiac ischemia, compared with 72% of patients who had primary ST-segment and T-wave abnormalities (p < 0.001) and 36% of those who had other ECG abnormalities (p < 0.001). Overall, the ECG-LVH patients were one-third less likely than the patients who did not have ECG-LVH to have had acute cardiac ischemia, after controlling for other predictors of acute ischemia by logistic regression (relative risk = 0.66, 95% CI 0.46 to 0.94). The patients who had ECG LVH were only one-fourth as likely to have had acute myocardial infarctions as were the patients presenting with primary ST-segment and T-wave changes (12% vs 48%, p < 0.001). Instead, a much larger proportion had had congestive heart failure or hypertension. The admitting physicians had identified ECG-LVH poorly on the admitting ECGs: only 22% of those who had ECG-LVH had been correctly identified, and for more than 70%, the secondary ST-segment and T-wave changes of ECG-LVH had been read as being primary. The short-term mortality for the patients who had ECG-LVH was 7.5%. This was intermediate between the mortality for patients who had primary ST-segment and T-wave abnormalities (10.6%) and those who had other ECG abnormalities (5.1%). Mortality was not affected by whether the admitting physician had recognized ECG-LVH initially. CONCLUSION: ECG-LVH was not a benign ECG finding among the patients who had presented with symptoms suggesting an acute cardiac ischemic syndrome: short-term mortality among the patients who had ECG-LVH (7.5%) approached that for the patients who had primary ST-segment and T-wave abnormalities (10.6%, p = 0.10). However, the patients who had ECG-LVH were one-third less likely to have had any acute cardiac ischemia than were the patients who did not have ECG-LVH, after logistic regression was used to control for other predictors of acute ischemia. Specifically, acute myocardial infarction was only one-fourth as likely when LVH was present on the admitting ECG (12%) as it was when primary ST-segment and T-wave abnormalities were present (48%, p < 0.001). Instead, congestive heart failure and hypertensive heart disease were more common. Thus, routine use of thrombolytic therapy for patients who have ECG-LVH does not seem warranted. ECG-LVH was poorly recognized (in only 22% of cases) by the physicians in the present study. Better recognition of this common ECG finding may lead to more effective patient management. PMID- 7876949 TI - Revascularization after acute myocardial infarction: impact of hospital teaching status and on-site invasive facilities. AB - OBJECTIVE: To investigate the influence of hospital teaching status and service availability on rates of revascularization following myocardial infarction. DESIGN: Retrospective cohort study based on province-wide hospital discharge abstracts. SETTING: All acute care hospitals in Ontario, Canada's most populous province (9.7 million). PATIENTS: Patients admitted to hospital between April 1, 1991, and September 30, 1991, with a principal diagnosis of acute myocardial infarction. MEASUREMENTS: The odds of a patient's having been referred for revascularization (angioplasty or bypass surgery) within six months of a myocardial infarction were calculated based on the type of hospital to which he or she had initially presented, defined as "teaching" or "nonteaching" or as having or not having interventional facilities on-site (cardiac catheterization and/or revascularization). Odds ratios were adjusted for potential confounding variables, and for possible joint effects of teaching status and on-site interventional capabilities. RESULTS: The patients were more likely to have had revascularization (OR 1.79; 95% CI 1.47-2.14, p = 0.0001) when they had been admitted to a teaching hospital, and independently were more likely to have been referred for revascularization (OR 1.34; 95% CI 1.09-1.66, p = 0.0067) when they had been admitted to a hospital with on-site interventional facilities. There was no interaction between teaching status and service availability regarding referral for revascularization. CONCLUSION: Teaching status is an important determinant of revascularization following acute myocardial infarction and is independent of service availability, which also influences revascularization rates. PMID- 7876950 TI - Evaluation of a simple office-based strategy for increasing influenza vaccine administration and the effect of differing reimbursement plans on the patient acceptance rate. AB - OBJECTIVE: To study an office-based strategy for increasing influenza vaccine delivery to high-risk patients at a university hospital general medicine practice. DESIGN: Historically controlled study of physician practices in an outpatient general medicine setting. SETTING: A group practice with two separate offices: a fee-for-service (FFS) office, where the patients pay the cost of immunizations, and a health maintenance organization (HMO)-styled office, where the costs for immunizations are fully covered by the insurer. PATIENTS: All outpatients seen at each practice setting from October to December, 1991. INTERVENTION: For each patient visit, a simple reminder data sheet was completed by the clinician detailing the vaccination eligibility (Centers for Disease Control and Prevention criteria) and status of the patient, the reasons for failure to vaccinate eligible patients, and 1990 vaccination information. RESULTS: During the study period, 511 patients were seen by the practice (353 in the FFS office, 158 in the HMO office). 297 patients (58%) were eligible for vaccination; 219 in the FFS office, 78 in the HMO office (p < 0.01). At the end of the study period, 73% of all the eligible patients were vaccinated: 67% of the FFS patients vs 90% of the HMO patients (p < 0.01). 22% of the eligible patients refused vaccination: 27% in the FFS office vs 9% in the HMO office (p < 0.01). 11% of the eligible FFS patients vs 0% of the eligible HMO patients refused vaccination due to vaccine cost (p < 0.05). Of the eligible patients seen at the two offices in both 1990 and 1991. 50% were vaccinated in 1990 (preintervention) vs 66% in 1991 (postintervention) (p < 0.01). CONCLUSIONS: As shown in this study, a simple, low-cost office-based reminder system can significantly increase the influenza vaccination rate for high-risk outpatients and can help meet national vaccination rate goals. Vaccine cost to patients may be a barrier to vaccine acceptance, in some cases. PMID- 7876951 TI - One-year outcome for patients with a chief complaint of dizziness. AB - OBJECTIVE. To determine the one-year outcome for patients with a chief complaint of dizziness that had persisted at least two weeks. DESIGN: Prospective cohort study. SETTING: Federal teaching hospital. PATIENTS: 100 dizzy patients and 25 control subjects. MEASUREMENTS: The primary outcome was dizziness status (improved or not improved); the secondary outcomes were morbidity and health care utilization. RESULTS: The dizziness resolved for 18 patients, whereas the status improved for 37, stayed the same for 32, and worsened for 11, with two patients lost to follow-up. Thus, 55% of patients whose dizziness had not resolved two weeks after their initial visits improved over the subsequent 12 months. Logistic regression revealed four independent predictors of persistent dizziness at one year follow-up: dizziness due to psychiatric causes, dysequilibrium, vertigo other than benign positional vertigo, vestibular neuronitis, or migraine (odds ratio, 6.3; 95% CI, 2.1-18.6); daily dizziness (odds ratio, 6.4; 95% CI, 2.0 21.0); dizziness worse with walking (odds ratio, 3.0; 95% CI, 1.1-9.0); and patient had initially feared a serious illness (odds ratio, 0.25; 95% CI, 0.10 0.74). These four factors could be used to classify patients as having either a high (82%), medium (47%), or low (0%) likelihood of improvement at one-year follow-up. One patient died from heart failure, and none developed a serious disease for which dizziness had been a harbinger. Dizziness was not associated with an increased number of clinic visits. CONCLUSIONS: Among patients with a chief complaint of dizziness who are still symptomatic at two-week follow-up, more than half improve within a year. Clinical factors identify patients at higher risk for persistent dizziness. PMID- 7876952 TI - Evaluation of a multicenter ethics objective structured clinical examination. AB - The purpose of this study was to evaluate a six-station ethics objective structured clinical examination (OSCE) on a volunteer sample of 66 medical students and 33 residents from three Ontario medical schools. The internal consistency reliability was 0.46 and the median interrater reliability was 0.675 (range 0.30 to 0.89). The residents' scores were higher than those of the medical students (F = 2.24, 0.046). Also, the scores differed among the three schools (F = 3.19, p = 0.0004). The ethics OSCE has adequate interrater reliability and construct validity, but low internal consistency reliability. There are differences among the schools that may assist in ethics curriculum evaluation and development. PMID- 7876953 TI - Performance on the internal medicine second-year residency in-training examination predicts the outcome of the ABIM certifying examination. AB - For 223 residents from eight teaching hospitals, the results of the second-year in-training examination and the first-sitting certifying examination of the American Board of Internal Medicine were highly correlated. The results of the in training examination can serve residents as an important measure of their preparedness for certification and can be useful in identifying the need for more intensive self-study strategies during the subsequent one and a half years. PMID- 7876954 TI - How residents spend their time in clinic and the effects of clerical support. AB - The authors conducted a time study of residents in clinic to determine the effects of providing clerical assistance. The residents recorded their activities at 5-minute intervals at baseline and six months after hiring three clerical assistants. Before and after introduction of the clerical assistants, approximately 40% of the time was devoted to direct interaction with patients. Statistically significant improvements were observed in the availability of medical records (89% vs 100%) and the time spent looking up test results (5% vs 3% of the clinic time). The residents felt the clerical assistants greatly improved their clinic experience and the quality of patient care. PMID- 7876955 TI - The promotion of generalism in medicine: renaissance or recycling? PMID- 7876956 TI - The meaning of life expectancy: what is a clinically significant gain? PMID- 7876957 TI - Rebuilding the wheel: toward a resolution of the generalist-specialist dichotomy. PMID- 7876959 TI - "Iatrogenic polydipsia". PMID- 7876958 TI - Collaboration in education of primary care physicians. PMID- 7876960 TI - Development of Trypanosoma cruzi in Triatoma infestans: influence of temperature and blood consumption. AB - This work had 2 objectives. The first was to quantify Trypanosoma cruzi development within Triatoma infestans maintained at 2 different temperatures, using an experimental design that simulated the natural transmission process and, second, to learn how the vector blood consumption rate modifies the parasite's development. Two hundred and three, fifth-stage nymphs of T. infestans were infected with the X-1 strain of T. cruzi (about 10(4) trypanosomes/ml blood), maintained at 20 and 28 C, and daily offered the opportunity to feed on uninfected laboratory mice. From 24 hr to the 55th day after the infective meal, the total number of epimastigotes and rectal and fecal metacyclic trypomastigotes were counted. Epimastigote multiplication began on the first day after the infective meal at both temperatures. This parasitic stage developed similar population densities within the vector under both temperature regimes. Trypomastigotes appeared in the rectum and feces at 20 C, 32 and 24 days later, respectively, than at 28 C; however, once they became infective, insects developed similar population densities of fecal metacyclic forms. Blood consumption was related to epimastigote and rectal trypomastigote development at 28 C, but not to the number of trypomastigotes in the feces. A minimum of 120 and 180 mg of fresh blood consumed assured that all bugs developed epimastigotes and trypomastigotes. In spite of the delay in producing metacyclic forms at 20 C, the insect's infective capacity was similar at both temperatures. PMID- 7876961 TI - Relevance of a partial immunity-inducing anti-schistosomiasis vaccine in endemic areas. PMID- 7876962 TI - An improved method for isolating RNA from coccidian oocysts. AB - A method, based on the disruption of eimerian oocysts in a French pressure cell in the presence of guanidine isothiocyanate, has been developed to isolate large quantities of high quality total RNA efficiently. This procedure results in a 12.5-fold greater number of oocysts broken, and a 22-fold greater yield of total RNA than from disruption by conventional grinding in liquid N2. In addition, the RNA isolated by the French pressure cell method was of equal or superior quality when compared to RNA isolated by grinding. This procedure provides a significant improvement in RNA extraction from eimerian oocysts and will greatly facilitate the study of gene expression in this important group of parasites. PMID- 7876963 TI - Prevalence of viable Toxoplasma gondii tissue cysts and antibodies to T. gondii by various serologic tests in black bears (Ursus americanus) from Pennsylvania. AB - During the hunting season of 1993, hearts from 28 black bears (Ursus americanus) from Pennsylvania were examined for Toxoplasma gondii infection. Serum samples from heart blood were examined for T. gondii antibodies by the use of the modified agglutination test (MAT), the Sabin-Feldman dye test (DT), the latex agglutination test (LAT), and the indirect hemagglutination test (IHA). One hundred grams of myocardium from each bear were bioassayed in mice. Approximately 500 g of myocardium from 11 bears were fed to 11 cats, and feces from those cats were examined for T. gondii oocysts. Toxoplasma gondii MAT antibodies (> or = 1:40) were found in 22 bears in titers of 1:40 (4 bears), 1:80 (3 bears), 1:160 (7 bears), 1:320 (4 bears), and > or = 1:2,000 (4 bears). Antibodies to T. gondii by DT (> or = 1:10), LAT (> or = 1:32), and IHA (> or = 1:64) tests were found in 21, 9, and 6 bears, respectively. All 6 bears that did not have T. gondii antibodies in MAT were also negative in DT, IHA, and LAT. Viable T. gondii was isolated from 3 bears by bioassays in mice and from an additional 7 bears by bioassays in cats. All 10 bears that had viable T. gondii had MAT and DT antibodies but only 6 and 5 of them had antibodies by LAT and IHA, respectively. PMID- 7876964 TI - Thin-layer chromatographic and histochemical analyses of neutral lipids in the intramolluscan stages of Leucochloridium variae (Digenea, Leucochloridiidae) and the snail host, Succinea ovalis. AB - Thin-layer chromatographic and histochemical analyses were used to analyze neutral lipids in the intramolluscan larval stages of Leucochloridium variae and in tissues of the snail host Succinea ovalis. Thin-layer chromatography showed that the major neutral lipids in uninfected snails were triacylglycerols and free sterols. The major neutral lipids in brood sacs minus their encysted metacercariae and in sporocysts were triacylglycerols and free sterols. Encysted metacercariae showed a significant free fatty acid fraction in addition to triacylglycerols and free sterols. Residual snail tissue (mainly head, foot, and visceral mass) from infected snails from which parasites were removed showed only a free sterol fraction. Histochemical staining of tissues with oil red O (ORO) showed the presence of neutral lipid droplets in the brood sac and sporocyst walls and mainly in the suckers, parenchyma, and excretory system of the encysted metacercariae. The residual snail tissue was ORO negative. PMID- 7876965 TI - Therapeutic efficacy of paromomycin in immunosuppressed adult mice infected with Cryptosporidium parvum. AB - The intent of this study was to evaluate the therapeutic efficacy of paromomycin in immunosuppressed adult C57BL/6N mice infected with Cryptosporidium parvum. Seven groups of 10 mice/group were used. Groups 1, 2, and 7 served as normal, toxicity, and placebo controls, respectively. Groups 2-7 were immunosuppressed with dexamethasone phosphate administered ad libitum in drinking water. Groups 3 7 were infected with C. parvum on day 7 postimmunosuppression. Groups 3-6 were treated by administering paromomycin per os for 10 consecutive days, beginning on day 10 postinfection, at dosage levels of 0.25, 0.5, 1, and 2 g/kg/day, respectively. Paromomycin was judged to be nontoxic at the dosage levels used. Groups 1 and 2 remained uninfected while groups 3-7 began shedding oocysts by day 3 postinfection. Paromomycin was therapeutically effective against C. parvum at 1 and 2 g/kg/day as determined by significant reductions in fecal oocyst shedding (P < 0.01), parasite colonization (P < 0.05), and villus atrophy (P < 0.05) in the ilea and terminal ilea of infected mice. We conclude that paromomycin may be useful in the treatment and palliation of cryptosporidiosis. PMID- 7876966 TI - Efficacy of moxidectin oral gel against Onchocerca cervicalis microfilariae. AB - During a series of dose-titration experiments designed to evaluate the efficacy of moxidectin oral gel against equine gastrointestinal parasites, infection with Onchocerca cervicalis was diagnosed in 25 of 82 ponies prior to treatment. Microfilariae were identified in full-thickness skin biopsies taken from the ventral midline. Treatment with moxidectin in single doses of 300, 400, or 500 micrograms/kg of body weight was 100% effective in eliminating microfilariae from 20 skin biopsies taken 14 days posttreatment, whereas 5 microfilaria-positive ponies in 2 control groups remained positive following placebo treatment. No adverse reaction was seen in any pony following treatment with moxidectin or the vehicle control. PMID- 7876967 TI - Further characterization of the TS-4 temperature-sensitive mutant of Toxoplasma gondii in mice. AB - Maternal transmission of Toxoplasma gondii infection to fetuses is important in human and veterinary medicine. Animals, including mice, have been successfully vaccinated with living tachyzoites of the avirulent, nonpersistent, TS-4 temperature-sensitive mutant of T. gondii and have survived challenge infections. We examined in the murine model the persistence of TS-4 infection, transplacental and transmammary transmission, and virulence in neonates. Bioassays of mouse tissues and histological examination of tissues indicated that no viable organisms were present beyond 14 days after inoculation in adult female mice. The TS-4 mutant was not transmitted transplacentally in mice inoculated at 5, 10, or 15 days of gestation and not transmammarily transmitted in mice inoculated 2 days postpartum. Four groups of mouse pups were inoculated subcutaneously with 2 x 10(4), 2 x 10(5) tachyzoites, or with Hanks' balanced salt solution at 2, 3, or 10 days of age. Severe clinical disease and death were observed in 2- or 3-day old mice and moderate to severe disease was observed in the 10-day-old mice. Results indicate that the TS-4 mutant can cause disease in young nursing mice but is avirulent for pregnant or nonpregnant adult mice. PMID- 7876968 TI - Recruitment-driven, spatially discontinuous communities: a null model for transferred patterns in target communities of intestinal helminths. AB - Populations and therefore communities of intestinal helminths of vertebrates are fueled by recruitment of new individuals from outside the host. The source of new individuals is often an intermediate host that harbors several infective propagules of 1 or more species. Hence these source communities are transmitted in packets of infective propagules to target communities in definitive hosts. Packets not only provide recruits to target communities, but, because a packet of propagules possesses its own structure, it may also transmit structure to the target community. We use this system to examine the contribution that structure in the source pool of propagules makes to the structure of recruitment-driven target populations and communities. By treating the dynamics of such target populations and communities as immigration-death processes, we conclude: (1) Unlike a birth-driven population a recruitment-driven target population will grow to an asymptotic limit even in the absence of density-dependent processes or reaching carrying capacity; (2) the frequency distribution of the number of recruits entering target populations will determine the frequency distribution of adults in target populations; (3) interspecific associations among species in the source community will be transmitted to target communities, but the magnitude of the transmitted associations will depend upon the relative survival rates of the species; and (4) for associations of equal magnitude in a source community, the magnitude of a transferred negative association will be less than the magnitude of a positive association in a target community. Two examples of source communities in salt marsh crabs reveal that source infracommunities exist with the hypothesized structure. Further, the source helminth communities display a greater number of positive than negative interspecific associations. The inequity in transfer and the existence of a greater proportion of positive associations in source communities may explain the widespread occurrence of excess positive associations that has been noted in recruitment-driven communities. PMID- 7876969 TI - Hairworms (Nematomorpha: Gordioidea) infecting New Zealand short-horned grasshoppers (Orthoptera: Acrididae). AB - A total of 282 short-horned grasshoppers (Acrididae) was collected in a mountainous area of New Zealand's South Island and examined for hairworm (Nematomorpha) infections. Thirteen percent of female Sigaus obelisci and 3% of female S. australis harbored hairworms; males of both species, as well as male and female S. campestris, were all uninfected. All hairworms recovered belong to the species Euchordodes nigromaculatus, previously known only from wetas (Orthoptera: Stenopelmatidae). No size differences were observed between infected and uninfected grasshoppers, and there was no relationship between host size and worm length. This is the first substantiated report of nematomorphs in grasshoppers in New Zealand. PMID- 7876970 TI - Infection characteristics of an Ecuadorian Trypanosoma cruzi strain with reduced virulence. AB - A human isolate of Trypanosoma cruzi obtained from Guayaquil, Ecuador (Guayas strain) was examined for its infectivity of the resistant C57Bl/6 (B6) and the susceptible C3H (He) mouse strains and compared to infection with the known virulent Brazil strain. C3H mice were capable of surviving acute Guayas infection, whereas the Brazil infection was fatal for this mouse strain. Both C3H and B6 mice showed a greatly reduced (over 10-fold) parasitemia during Guayas infection compared to Brazil infection. Histologic examination of heart tissue from Guayas-infected B6 and C3H mice indicates little inflammation, unlike what is typically seen in B6 mice chronically infected with the Brazil strain. There appears to be no remarkable difference in the anti-parasite antibody responses (as measured by ELISA and western blot) in mice infected 100 days with Guayas or Brazil parasites. Western blot analysis of the anti-heart response indicates no response during Guayas infection to a 43-kDa heart tissue glycoprotein that is a target of antibodies from B6 mice infected with Brazil strain. The Guayas strain, therefore, provides an infection that generates a low parasitemia and strong anti parasite responses in the absence of specific anti-heart autoimmunity and obvious myocarditis. In vitro infection characteristics of these 2 parasite strains were studied in cultures of macrophages, myocytes, and fibroblasts by microscopic examination of stained slide cultures. In both short-term (24 hr) and long-term (15 day) experiments, Brazil strain infection was shown to have a greater infection rate with a higher number of parasites per cell than Guayas infection for all host cell types.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876971 TI - Toxoplasma gondii antibodies in woodchucks (Marmota monax) from Pennsylvania. AB - Serum samples from 545 woodchucks Marmota monax from 22 counties in Pennsylvania were examined for antibodies to Toxoplasma gondii by the modified direct agglutination test. Fifty-one woodchucks (9.4%) had antibodies to T. gondii, with 10% at dilutions of 1:25, 2% at dilutions of 1:50, and 4% at dilutions of 1:500. This is the first report of T. gondii antibodies in woodchucks. PMID- 7876972 TI - Enzyme-linked immunosorbent assay for detection of serum antibody to Blastocystis hominis in symptomatic infections. AB - An enzyme-linked immunosorbent assay was devised in order to search for antibodies against Blastocystis hominis in infected humans. Reaction proteins were obtained from washed, axenic B. hominis cells, as sonicate. Sonicate was diluted to provide 17 and 34 micrograms of protein per well. Dilutions of patients' sera were applied, followed by phosphatase-conjugated goat anti-human serum and phosphatase substrate. Color was measured at 405 microns wavelength. Immunoglobulin G antibodies to high titers were found. Of 30 sera tested from 28 patients, 3 were negative at the 1/50 threshold dilution, 8 were positive at 1/50, 3 at 1/100, 2 at 1/200, 3 at 1/400, 6 at 1/800, and 5 at 1/1,600. Normal sera (42 blood bank sera) were all negative at 1/50. Each serum was subjected to multiple testing. Duplicate tests were included for each run, and runs were made from 4 to 6 for each serum. Blastocystis hominis is increasingly recognized to be a cause of human enteric disease, with symptoms often like those in giardiasis. Demonstration of strong antibody response is consistent with this view. PMID- 7876973 TI - Cytosystematics of five North American Amblyomma (Acarina: Ixodidae) species. AB - The karyotypes of 5 species of Amblyomma ticks found in North America were examined for the presence and location of constitutive heterochromatin (C-bands). All specimens examined had 20 autosomes and an XX:XO sex-determining system, with the X being the largest element in the karyotype. Except as noted in text, the autosomes of all species were acrocentric and heterochromatin was restricted to the centromeric region. The third largest autosome in 4 of the 5 species displayed a consistent band of heterochromatin just below the centromere; Amblyomma imitator displayed heterochromatin on the third largest pair of autosomes but in the form of an entire heterochromatic short arm. It is hypothesized that the third largest autosome could be the location of the nucleolar organizer region. Unique features of the C-banded karyotype that characterize and differentiate each species are presented. Similarity in the C banding pattern exists between Amblyomma americanum and Amblyomma maculatum (the C-band in the X chromosome) and Amblyomma cajennense and A. imitator (the extreme subacrocentric X chromosome). The placement of Amblyomma inornatum remains difficult and cannot be clearly determined based on the placement of heterochromatin. PMID- 7876975 TI - Infection of Tribolium beetles with a tapeworm: variation in susceptibility within and between beetle species and among genetic strains. AB - Host susceptibility and resistance to parasites are often hypothesized to be genetically variable traits. We tested 2 species of Tribolium flour beetles for among-strain variation in susceptibility to the rat tapeworm Hymenolepis diminuta. Twelve genetic strains of Tribolium confusum and 11 strains of Tribolium castaneum were examined. We found T. castaneum was more susceptible to the tapeworm than T. confusum. There was significant among-strain and between-sex variation for both beetle species in infection intensity and prevalence. Among vial variation was marginally significant. These results add to evidence that host susceptibility to a parasite is a genetically variable trait. We view these results as important findings for understanding natural selection on host parasite interactions. Traits that are genetically variable can respond to natural selection. Thus, if a beetle's susceptibility to the tapeworm is correlated with fitness and heritable, susceptibility can evolve. Susceptibility is likely to be pleiotropic and have important consequences on issues ranging from parasite transmission to host species interactions and community structure. PMID- 7876974 TI - Natural occurrence and characterization of the Lyme disease spirochete, Borrelia burgdorferi, in cotton rats (Sigmodon hispidus) from Georgia and Florida. AB - This is the first report of natural infection by Borrelia burgdorferi in the cotton rat Sigmodon hispidus. Nine B. burgdorferi isolates were obtained from ear tissues, urinary bladders, or both, by culturing tissues in BSKII medium. The rat from which the SI-3 isolate was cultured was from the same site (Sapelo Island, Georgia) as an infected cotton mouse Peromyscus gossypinus and Ixodes scapularis tick reported previously. The 8 B. burgdorferi isolates from rats in Florida included 1 (AI-1) from Amelia Island, 1 (FD-1) from Faver-Dykes State Park, and 6 (MI-3 through MI-8) from Merritt Island. The distance between Sapelo Island and Merritt Island is approximately 400 km. All B. burgdorferi isolates were characterized by indirect immunofluorescence using monoclonal antibodies to OspA (H3TS, H5332) and OspB (H5TS, H6831), polymerase chain reaction detection of specific B. burgdorferi B-31 DNA target sequences (ospA, fla, and a random chromosomal sequence), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of spirochetal proteins. The phenotypic and genotypic characteristics of the isolates are discussed, as well as the probable importance of the cotton rat as a reservoir for B. burgdorferi in the southern United States. PMID- 7876976 TI - Comparison of two strains of Schistosoma mansoni with respect to the sites and kinetics of immune elimination in irradiated cercaria-immunized mice. AB - A comparison was made of the sites of elimination of NMRI and Mill Hill strains of Schistosoma mansoni in C57BL/6J mice previously immunized with 50 krad gamma irradiated cercariae of the homologous strain. In the first experiment, the fate of percutaneous challenge infections with 75Se-labeled cercariae was evaluated by autoradiography of tissue squashes and hepatic portal perfusion. For both strains of parasite, migration from skin to lungs was delayed but not reduced in immunized mice relative to controls, with immune elimination taking place at some point after migration to the lungs. In a second experiment, resistance to the Mill Hill strain of S. mansoni was compared in mice challenged by percutaneous infection with cercariae and by intravenous injection with lung schistosomula. Both types of challenge were shown to be vulnerable to immune elimination. We conclude that under the conditions employed in this study, there is no significant difference between the NMRI and Mill Hill strains of S. mansoni in the patterns of migration and elimination, with most or all elimination in both control and immunized mice taking place after migration from the skin. PMID- 7876977 TI - Toxoplasma gondii in Iowa sows: comparison of antibody titers to isolation of T. gondii by bioassays in mice and cats. AB - Hearts of 1,000 pigs killed at an abattoir in Iowa were bioassayed for the prevalence of tissue cysts of Toxoplasma gondii. One hundred grams of cardiac muscle from each pig was homogenized, digested in pepsin solution, and bioassayed in 10 mice. Five hundred grams of heart tissue from each of a subset of 183 pigs was also bioassayed in cats. Serum collected from the heart from each pig was assayed for anti-T. gondii antibodies in the modified agglutination test using formalin-fixed whole tachyzoites. Anti-T. gondii antibodies were found in 22.2% of pigs. Viable T. gondii was isolated from a total of 170 pigs; from 50 hearts by bioassay in mice, from 58 hearts by bioassay in both mice and cats, and from 62 pigs by bioassay in cats only. The success of isolation in cats (65.6%) was approximately twice that in mice (31.7%). Percentage of isolations of T. gondii with respect to reciprocal antibody titers (in parentheses) in pigs was: 3.7% (< 20), 37.1% (20), 38.1% (40), 60% (80), 75% (200), 77% (400), 83% (800), and 75.8% (> or = 2,000 to 16,000). PMID- 7876978 TI - Protection of calves with a vaccine against Cryptosporidium parvum. AB - Cryptosporidium parvum causes enteric infection and diarrhea in calves, other species of economically important livestock, and humans. There are no effective treatments currently licensed for this parasite, and preventive measures are difficult. In addition to direct economic losses to the cattle industry, infected calves may contaminate water supplies with oocysts and contribute to human cryptosporidiosis. We have developed a vaccine offering partial protection against C. parvum infection in calves. Nine calves received an oral preparation of lyophilized C. parvum oocysts shortly after birth, and 10 calves served as nonvaccinated controls. All calves received colostrum. At 1 wk of age, all calves were administered 10(4) viable C. parvum oocysts orally. Clinical disease and oocyst shedding were monitored daily. Mean duration of diarrhea was 4 days for control calves and 1.7 days for vaccinated calves. Mean duration of oocyst shedding was 5.3 days for control calves and 2 days for vaccinated calves. These differences were statistically significant and suggest that this vaccine has the potential to reduce diarrhea and oocyst shedding caused by C. parvum. PMID- 7876979 TI - Plasmodium berghei: production and quantitation of hepatic stages derived from irradiated sporozoites in rats and mice. AB - Immunization with irradiated-attenuated malaria sporozoites has been shown to protect both rodents and humans against a homologous sporozoite challenge. Irradiated-attenuated sporozoites retain their capacity to invade hepatocytes and transform into trophozoites without undergoing complete schizogony. As a result, the minute size of these trophozoites (4-8 microns) makes their detection by conventional microscopy difficult. An additional problem lies in obtaining sufficient quantities of exoerythrocytic stages of attenuated parasites in vivo to study their antigenic repertoire and the sequence of events that occur after immunization of hosts. We have used a previously described method of inoculating Plasmodium berghei sporozoites directly into specific liver lobes (HPBI = hepatic portal branch inoculation) to improve parasite yields. Comparing HPBI with tail vein inoculation of sporozoites in Brown Norway rats and C57BL/6 mice revealed up to a 6-fold increase in hepatic parasite yields by HPBI method. The inoculation of 3 x 10(6) irradiated sporozoites via HPBI yielded 139 +/- 2 and 69 +/- 2 exoerythrocytic parasites per cm2 of liver in Brown Norway rats and C57BL/6 mice, respectively. The HPBI method therefore not only facilitates visualization of a large number of irradiated hepatic stage parasites within the defined lobes of the liver but also provides ample numbers of parasites for immunization and for immunological analysis. PMID- 7876980 TI - Coccidian parasites (Apicomplexa) from snakes in the southcentral and southwestern United States: new host and geographic records. AB - Four hundred thirty-five leptotyphlopid, colubrid, elapid, and viperid snakes were collected from various localities in Arkansas, New Mexico, Oklahoma, and Texas, and their feces were examined for coccidian parasites. Of these, 131 (30%) were passing oocysts or sporocysts of at least 1 coccidian; 88 (67%) of the infected snakes had only 1 species of coccidian when they were examined. Aquatic and semiaquatic snakes accounted for 48% of the infections, whereas strictly terrestrial snakes comprised the other 52%. There was more than a 2-fold difference in prevalence among these 2 groups as 63 of 129 (49%) of the aquatic and semiaquatic snakes versus 68 of 306 (22%) of the terrestrial snakes harbored coccidia. Most terrestrial snakes were infected by species of Caryospora and Sarcocystis that are either facultatively or obligatorily heteroxenous. The aquatic and semiaquatic species most often harbored eimerians. Attempts to transmit some of the Sarcocystis spp. experimentally from Crotalus atrox to Mus musculus, Peromyscus leucopus, Peromyscus maniculatus, or Microtus ochrogaster were unsuccessful. This report documents 27 new host and several distributional records for coccidians from snakes in the southcentral and southwestern United States. PMID- 7876981 TI - Larval anisakid nematodes of Japanese common squid (Todarodes pacificus) from the Sea of Japan. AB - Two species of third-stage larvae of the family Anisakidae are described from the Japanese common squid (Todarodes pacificus Steenstrup) from the Sea of Japan. The larvae of 1 of them, Anisakis simplex (Rudolphi, 1809), commonly occur encapsulated in the viscera of squid, whereas those of another 1, identified as Lappetascaris sp., are found free in the mantle musculature. The latter, characterized by the presence of a very long ventricular appendix, a conspicuous esophageal gland, and the structure of the cephalic end (presence of sclerotized supports of lip anlagen), previously were reported by various authors as members of the genera Contracaecum, Thynnascaris, or Hysterothylacium. It appears that the larvae form the mantle of squid belong to a hitherto undescribed Lappetascaris species whose adults parasitize an, as yet unknown, predatory marine fish. PMID- 7876982 TI - Taxonomic notes on Polyacanthorhynchus kenyensis (Acanthocephala: Polyacanthorhynchidae) from Lake Naivasha, Kenya. AB - The original description of Polyacanthorhynchus kenyensis Schmidt and Canaris, 1967 from 2 species of fish in Lake Naivasha, Kenya was primarily based on measurements of 2 male cystacanths. That description is herein emended based on the availability of a larger number of immature worms of both sexes obtained from the freshwater teleosts Orechromis leucostictus, Tilapia zillii (new paratenic host records), and Micropterus salmoides. A secretory function for the apical organ is suggested. PMID- 7876983 TI - Worm development in hamsters infected with unisex and cross-mated Schistosoma mansoni and Schistosoma haematobium. AB - Schistosoma mansoni and Schistosoma haematobium coexist in Egypt and in other areas in Africa, and people frequently are infected with parasites of both species. The effects of the interactions between worms of both sexes of the 2 species on development and egg laying were evaluated in vivo by infecting hamsters with cercariae from Biomphalaria alexandrina and Bulinus truncatus snails infected with single miracidia. In hamsters with unisex infections, male worms of both species were small. Schistosoma mansoni females were stunted and partially mature but did not contain eggs. Schistosoma haematobium females, though stunted, sometimes contained and laid small eggs, which were deposited in the liver, but few of which contained motile embryos. This suggests that unisexual infection with S. haematobium female worms produces a risk for liver damage due to egg deposition in tissues. Both S. mansoni and S. haematobium females that mated with males of the heterologous species were significantly larger than females from unisexual infections; they were sexually mature and possessed eggs in the uterus. The eggs in the liver homogenates of cross-specific infected hamsters contained fully developed miracidia that hatched in filtered pond water. PMID- 7876984 TI - Serendip deborahae n. gen. and n. sp. (Eucestoda: Tetraphyllidea: Serendipidae n. fam.) in Rhinoptera steindachneri Evermann and Jenkins, 1891 (Chondrichthyes: Myliobatiformes: Myliobatidae) from southeastern Ecuador. AB - Cestodes collected in spiral valves of Rhinoptera steindachneri from the southern coast of Ecuador represent an undescribed species of Tetraphyllidea. The new species has bothridia possessing septa but lacking apical suckers. It is diagnosably distinct from all other tetraphyllidean genera by possessing a scolex comprising 4 triangular bothridia that are fused together forming a platelike structure, each of which is subdivided by 2 simple and 1 bifurcating septa radiating from its base and ringed by marginal loculi; therefore, a new genus is proposed for it. By exhibiting some degree of bothridial fusion, testes arranged in 2 layers in the proglottis and postovarian testes, the new species appears to be a member of a clade containing Dioecotaenia, Duplicibothrium, and Glyphobothrium. The new species possesses vitelline fields that converge dorsally in each proglottis, except for the ovarian and terminal genitalia areas, a feature that has been reported previously only in Duplicibothrium and Glyphobothrium. Furthermore, Duplicibothrium and Glyphobothrium, like the new species, are markedly protandric. Therefore, we propose that Duplicibothrium, Glyphobothrium, and the new species comprise the sister group of the Dioecotaeniidae, and propose a new family name for the clade. Tritaphros is rejected as a possible sister group for the clade; suggested alternatives include some species of Caulobothrium, Rhodobothrium, or some members of the Phyllobothrium centrurum group. PMID- 7876985 TI - Libyostrongylus dentatus n. sp. (Nematoda: Trichostrongylidae) from ostriches in North America, with comments on the genera Libyostrongylus and Paralibyostrongylus. AB - Libyostrongylus dentatus sp. n. is described from ostriches on farms from North Carolina and Texas. Nematodes were recovered from the posterior proventriculus and under the koilon lining of the gizzard; the parasites occurred in mixed infections with Libyostrongylus douglassii. The species is distinguished from congeners by the presence of a prominent, dorsal, esophageal tooth; in males by the structure of the dorsal ray and spicules; and in females by small eggs (52-62 microns in length), a sublateral vulva situated at 93% of the body length from the anterior, and a strongly curled, digitate, tail with cuticular inflations at the anus. Conflicts in the generic diagnoses of Libyostrongylus and Paralibyostrongylus were apparent, based on the structure of the dorsal ray or position of rays 3-5 of the copulatory bursa. These can only be resolved based on phylogenetic analyses of the 11 nominal species referred to these genera. PMID- 7876986 TI - Angiostoma schizoglossae n. sp. (Nematoda: Angiostomatidae) from the New Zealand endemic slug Schizoglossa novoseelandica (Gastropoda: Rhytididae). AB - Angiostoma schizoglossae n. sp. is described from Schizoglossa novoseelandica Pfeiffer collected from a forest in central North Island, New Zealand. Angiostoma schizoglossae is distinguished from other Angiostoma species with peloderan caudal alae in the Northern Hemisphere, by combined characters of subtriangular mouth, lack of lateral alae, and, in the male, variation in position and number of the pedunculate papillae. Its occurrence among the New Zealand endemic land snail fauna extends the known range of the monogeneric Angiostomatidae to include both the Holarctic and Southwest Pacific regions. This is suggestive of the ancient emergence of the Angiostomatidae and their long association with terrestrial molluscs. A key is provided for identification of all known Angiostoma species. PMID- 7876987 TI - Protection against murine cerebral malaria by dietary-induced oxidative stress. AB - Feeding 20% (w/w) menhaden-fish oil in a standard laboratory chow diet for 4 wk partially protected CBA/CaJ mice from the central nervous system consequences of infection with Plasmodium berghei (ANKA). Full protection (complete survival for 14 days postinfection) could be obtained by feeding a purified pro-oxidant vitamin E-deficient diet containing 4% (w/w) menhaden oil (MO - VE diet). The purified pro-oxidant MO - VE diet also exerted a pronounced suppressive effect against the parasite (depressed 6-day parasitemias). The anitmalarial effect of the MO - VE diet could be prevented by supplementing the diet with vitamin E or with either of 2 synthetic antioxidants, N,N'-diphenyl-p-phenylenediamine or probucol. These results suggest that the fish oil exerts its antimalarial effect by imposing a dietary-induced oxidative stress on the infected host erythrocyte, the parasite, or both. Nutritional manipulation of host oxidative stress status may be a useful adjunct therapy in patients undergoing treatment with pro-oxidant antimalarials such as drugs of the qinghaosu family. PMID- 7876988 TI - The oligosaccharide composition of human milk: temporal and individual variations in monosaccharide components. AB - Oligosaccharides are an important component of human milk, but little is known about variations in their composition. The aim of this study was to determine the temporal and inter-individual variations in carbohydrate composition of human milk during the first 3 months of lactation. Serial milk samples of 10 mothers (eight full-term and two preterm births) were analyzed to determine the concentration of lactose and three monosaccharide components derived from the non lactose carbohydrate: sialic acid, N-acetylglucosamine, and fucose. In full-term milk, sialic acid and N-acetylglucosamine were found to decrease significantly (p < 0.05) from weeks 1 to 13 postnatally. On average (mean +/- SD), sialic acid decreased by 71% (from 879 +/- 157 to 256 +/- 82 mg/L; p < 0.05) and N acetylglucosamine by 56% (from 1,459 +/- 282 to 646 +/- 214 mg/L; p < 0.05), while fucose decreased by only 35% (from 660 +/- 192 to 432 +/- 180 mg/L; p > 0.05). On average, lactose concentration increased by 17% over the same period, from 55.4 +/- 4.2 g/L in week 1 to 64.9 +/- 2.3 g/L at 3 months. Preterm milk contained higher concentrations of each component, but temporal changes were similar to those seen in full-term milk. Apart from temporal changes, there were large inter-individual differences in oligosaccharide composition: fucose varied four-fold, sialic acid threefold, and N-acetylglucosamine two-fold among women at the same stage of lactation. The changes observed may simply reflect the aging of the cells responsible for milk secretion, but they are also consistent with a programmed adaptation of the milk composition to the needs of the infant. PMID- 7876989 TI - Potential aluminium toxicity in infants fed special infant formula. AB - Aluminium was measured in samples of plasma and samples of feed obtained from 74 infants with normal renal function established on various feeds (breast, whey based, fortified whey-based, preterm, soy, and casein hydrolysate). All infants were bolus fed, and blood samples were collected midway between feeds. Aluminium was measured using electrothermal atomization and atomic absorption spectrometry. Mean aluminium concentrations in milks were as follows: breast, 9.2 micrograms/L [95% confidence interval (CI), 5.6-12.7]; whey-based, 165 micrograms/L (95% CI, 151-180); fortified, 161 micrograms/L (95% CI, 143-180); preterm, 300 micrograms/L (95% CI, 272-328); soy, 534 micrograms/L (95% CI, 470-598); casein hydrolysate, 773 micrograms/L (95% CI, 632-914). Mean plasma aluminium concentrations in infants receiving different milks were as follows: breast, 8.6 micrograms/L (95% CI, 5.6-10.6); whey-based, 9.2 micrograms/L (95% CI, 7.4-11.0); fortified, 10.3 micrograms/L (95% CI, 8.3-12.3); preterm, 9.7 micrograms/L (95% CI, 5.3-17.1); soy, 12.5 micrograms/L (95% CI, 5.0-20.0); casein hydrolysate, 15.2 micrograms/L (95% CI, 10.7-19.8). Mean plasma aluminium concentration was significantly different in infants fed casein hydrolysate formulae than in those fed breast milk (difference, 6.7 micrograms/L; 95% CI, 2.8-10.5; p = 0.028). We conclude that infants may be at risk from aluminium toxicity when consuming formula containing > 300 micrograms/L--in particular, casein hydrolysate formulae. We speculate that the aluminium compounds found in breast milk are more bioavailable than those found in other milks and that some constituents of infant formula affect aluminium absorption from the gut lumen. PMID- 7876991 TI - Insulin-like growth factor-I in celiac disease. AB - To contribute to the description of the physiopathological mechanisms of celiac disease, changes in insulin-like growth factor I (IGF-I) were followed-up in 21 children suspected of suffering from celiac disease. Thirteen children were suffering from celiac disease according to the original criteria of the European Society of Paediatric Gastroenterology and Nutrition. Ten celiac children changing from a gluten-containing to a gluten-free diet presented a significant rise in IGF-I (+1.54 mM per month). In a group of eight celiac children challenged with gluten, seven had a significant decrease in IGF-I (-1.11 mM per month), and five celiac children returning to the gluten-free diet after challenge with gluten had a marked but not significant increase in IGF-I (+1.7 mM per month). Eight children not suffering from celiac disease, but challenged with gluten, had a significant increase in IGF-I (+0.29 mM per month), corresponding to the expected age-dependent increase. The significant changes in IGF-I described under the diagnostic dietetic phases of celiac disease reflect the extent of growth retardation caused by the disease. IGF-I may be a supplementary aid in the diagnosis of celiac disease in describing individual changes under the dietetic phases. PMID- 7876990 TI - Effect of orally administered epidermal growth factor on intestinal recovery of neonatal pigs infected with rotavirus. AB - The effect of oral epidermal growth factor (EGF) on histological and biochemical changes in epithelium in the small intestine was studied in colostrum-deprived neonatal pigs. Forty-eight pigs were infected at 4 days of age with 2 x 10(7) plaque-forming units of porcine group A rotavirus and orally fed a simulated sow milk diet supplemented with 0.0, 0.5, or 1.0 mg/L recombinant human EGF. Sixteen noninfected pigs were fed a diet without EGF supplementation. Infected pigs developed severe diarrhea; they also consumed 25% less food and gained 60% less weight than noninfected pigs. Pigs were killed 8 days postinfection to collect samples at seven equidistant points in the small intestine. Rotavirus infection decreased villus height by 37% and reduced specific activity of lactase by 54%, of leucine aminopeptidase by 43%, and of alkaline phosphatase by 54% in the small intestine, compared with noninfected pigs. Only the supraphysiological dose of EGF (1.0 mg/L) consistently increased villus height in the proximal and mid-small intestine and lactase-specific activity in the mid-small intestine of rotavirus infected pigs. However, this dose was only partially effective in restoring intestinal mucosal dimensions and enzyme activities. Supplemental EGF did not hasten the resolution of diarrhea. These data indicate that high physiological levels of EGF are beneficial in stimulating recovery of epithelium in the small intestine following rotavirus infection. PMID- 7876992 TI - Catch-up growth in 60 children with celiac disease. AB - The growth pattern of 28 girls and 32 boys with celiac disease was analyzed up to the ages of 10 and 12 years, respectively. Fifty-four patients (90%) were diagnosed before 4 years of age and six patients (10%) between 5 and 9 years of age. At diagnosis, 18 of 60 patients (30%) had a height SD score below -2.0, and 45 of 59 patients (76%) had a weight-for-height below the median. The mean height SD score showed increasing growth retardation in the year before diagnosis, relatively quick catch-up growth in the year after diagnosis, and complete catch up in 2-3 years. Mean weight-for-height showed a progressive decrease 12-18 months before diagnosis, increased to a maximum at the end of the first year of therapy, and returned to normal 15 months after dietary treatment. Independent of age at diagnosis, initial degree of wasting, diagnostic delay, and strictness of gluten-free diet, catch-up growth was complete in this group of patients who were diagnosed before 9 years of age. PMID- 7876993 TI - Diagnostic accuracy of a new stick micromethod with which to measure antigliadin antibodies. AB - A new, simplified micromethod for semiquantitative determination of the antigliadin antibody (AGA) has been proposed. When the new stick method was used in a population of infants hospitalized for gastrointestinal problems, the results were virtually identical to those of the traditional method. PMID- 7876994 TI - Gastric emptying in children with gastric transposition. AB - Using the noninvasive technique of electrical impedance tomography (EIT), gastric emptying was studied in 12 children, aged 9 months to 17 years, who had undergone gastric transposition (six with pyloroplasty) for oesophageal replacement (seven oesophageal atresia, five severe caustic or peptic damage). In two patients, gastric antral electrical control activity was also studied using surface electrogastrography. Nine patients had problems on oral feeds (respiratory symptoms, feeding difficulties, vomiting, abdominal pain, symptoms suggesting dumping), whilst three were asymptomatic. All 12 patients were tested with a milk meal; in addition four (two with and two without dumping symptoms) were tested with a hypertonic glucose drink; gastric emptying of the milk meal was expressed as the percentage of the meal remaining in the stomach at 60 min (R60). Mean (+/- 2 SD) R60 was 54.6% (+/- 17.4%) in 12 healthy controls and 59.8% (+/- 83.2%) in the 12 patients. Gastric emptying was normal in one patient (R60, 42.6%), delayed in seven (mean R60, 91.2%; range, 74.4-100%), and accelerated in four (R60, 0%). The emptying rate was unrelated to the presence or absence of pyloroplasty. Furthermore, the emptying pattern was extremely irregular, suggesting that gastroesophageal as well as duodenogastric reflux episodes occurred in all patients. The hypertonic glucose drink induced dumping (50% of the meal emptied at 1-3 min) in all four patients, two of whom had delayed emptying of the milk meal, but the gastric antral electrical control activity occurred at the normal frequency of 0.05 Hz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7876995 TI - Oral rehydration solutions: increased water and sodium absorption by addition of a viscosity-enhancing agent in a rat model of chronic osmotic diarrhea. AB - Viscosity-enhancing agents such as carboxymethylcellulose (CMC) can alter absorption of solutes and fluid exchange in the small intestine. We investigated whether the standard World Health Organization oral rehydration solution (WHO ORS) with the addition of CMC would improve net water and sodium absorption in rats using an in vivo intestinal perfusion technique. Four WHO-ORS, containing either 0, 2.5, 5.0, or 10.0 g/L of CMC, were perfused in rats with a well-tested model of cathartic-induced chronic osmotic diarrhea (D) and in normal controls (C). In D rats, the ORSs with CMC improved sodium absorption at the three concentrations used (p < 0.01). The same effect was shown in C rats. Net water absorption was also enhanced in D rats given ORSs with CMC, although the changes in C animals were less marked. The improvement in sodium and water absorption in both C and D rats positively correlated with the log of relative ORS viscosity. Ultrastructural examination of tissues perfused with 10 g/L of CMC showed an extended brush border glycocalyx. This study indicates that CMC added to WHO-ORS in the perfused rat jejunum improves the effectiveness of the solution by increasing sodium and water absorption. PMID- 7876996 TI - The prevalence of Helicobacter pylori positivity in human immunodeficiency virus infected children. AB - To investigate the prevalence of Helicobacter pylori infection in pediatric patients infected with the human immunodeficiency virus, we sought to detect the presence of antibodies against this organism in 23 human immunodeficiency virus infected children of central African ethnic origin by means of a second generation enzyme-linked immunoassay (ELISA) test for the detection of immunoglobulin G (IgG) antibodies to Helicobacter pylori (Malakit Helicobacter pylori, Biolab, Limal, Belgium). They were compared to an asymptomatic control population matched for age and ethnic origin. Blood samples were taken during routine blood analysis before the monthly administration of intravenous gamma globulins in the human immunodeficiency virus-infected patients and during preoperative blood analysis in the control population. Despite the fact that most human immunodeficiency virus-infected patients had IgG antibodies against other frequently encountered pathogens, none of them had a positive serology for Helicobacter pylori, compared to 10 of 52 patients (19.2%) in the control population. This difference is statistically significant (p = 0.01). PMID- 7876997 TI - Plasma carnitine levels in cystic fibrosis. AB - Plasma carnitine concentrations were measured in 43 children and adults with cystic fibrosis (CF), and values were compared with those from normal controls. Clinically significant abnormalities of plasma carnitine concentration were not found in CF patients. The concentration of free carnitine was slightly but significantly elevated in CF patients, and the acylcarnitine concentration and acylcarnitine/free-carnitine ratio were slightly but significantly lower. Total carnitine concentrations were similar to those of controls. The CF patients did not have abnormal urinary acylcarnitines. Altered concentrations of free and esterified carnitine were not associated with nutritional status or with liver or pulmonary function. PMID- 7876998 TI - The renin-angiotensin-aldosterone system and vasopressin in early-stage liver cirrhosis after HBV infection in children. AB - We evaluated the dynamic response of renin, aldosterone, and vasopressin to intravenous water loading (20 ml 5% glucose/kg b.w.) in 12 children (aged 7-18 years) with postinflammatory liver cirrhosis after hepatitis B virus (HBV) infection. All of the patients had early-stage liver cirrhosis; according to Child's classification, nine patients had group A; three, group B cirrhosis. A group of 17 children with chronic persistent hepatitis served as the control. The diagnoses were confirmed in all of the patients by liver biopsy. The patients followed a diet containing 3 mmol NaCl/kg/day, maximum 100 mmol per day for 6 days. Water loading was performed in recumbency over approximately 45 min. Renin, aldosterone, and vasopressin, assayed by radioimmunoassay (RIA), were determined before, 1 h, and 5 h after starting the water load. Prestudy hormone levels were within normal range in both groups. Renin and aldosterone concentration change patterns were similar in both groups and characterized by suppression of hormone activity caused by central volume expansion and recovery to prestudy levels after 5 h. However, the pattern of change of vasopressin concentrations differed in the control and study groups. In contrast to that of the controls, volume expansion did not suppress vasopressin in the group with liver cirrhosis. We conclude that failure to suppress vasopressin activity after central volume expansion may be one of the early mechanisms responsible for water-electrolyte imbalance in liver cirrhosis in children. PMID- 7876999 TI - Chronic active hepatitis B infection in Romanian adoptees. PMID- 7877000 TI - Gastric inflammatory myofibroblastic tumor (inflammatory pseudotumor) in infancy: case report and review of the literature. PMID- 7877001 TI - Gastric xanthomas in a child. PMID- 7877002 TI - Dog hookworm: a cause of eosinophilic enterocolitis in humans. PMID- 7877003 TI - Pitfalls in the diagnosis of autoimmune hepatitis associated with liver and kidney microsomal proteins. PMID- 7877004 TI - Fatal hepatitis C in an infant born to a hepatitis C positive mother. PMID- 7877005 TI - Caroli's disease with congenital hepatic fibrosis and medullary sponge kidney. PMID- 7877006 TI - Fibrolamellar hepatocellular carcinoma: report of a case mimicking a liver abscess. PMID- 7877007 TI - Can we actively treat rotavirus gastroenteritis? PMID- 7877008 TI - Do bacterial cell wall polymers perpetuate chronic intestinal inflammation in the susceptible host?--role of cytokines. PMID- 7877009 TI - Ursodesoxycholic acid: effect on xanthomas in Alagille-Watson syndrome. PMID- 7877010 TI - Gastroesophageal reflux and asthma. PMID- 7877011 TI - Repair of congenital sternal clefts in adolescence and infancy. AB - Two cases of sternal cleft not associated with ectopia cordis are presented. An 11-year-old girl with a superior incomplete sternal cleft underwent reconstruction of the sternum with autologous rib, cartilage, and sternal periosteum. At the 1-year follow-up her sternal appearance was normal. The second patient, a full-term baby girl, had complete sternal cleft diagnosed by ultrasonography at 21 weeks' gestation. She underwent primary repair in the neonatal period and currently is asymptomatic with a normal-appearing sternum (10 months postoperatively). Primary repair in the neonatal period is the best type of management for this rare condition. For older patients, autologous repair is appropriate and avoids problems associated with the use of prosthetic materials. PMID- 7877012 TI - A rare case of truncal duplication. AB - A rare case of truncal duplication is presented in which the infant had an extra truncus with well-formed extremities, a hypoplastic thorax, and a small abdomen. The truncus was attached to the infant from the thorax to the umbilicus. Successful separation of the truncus and reconstruction of the thoracoabdominal wall defect were performed in the neonatal period. PMID- 7877013 TI - Primary antiphospholipid syndrome in a child with lower extremity arterial thrombosis. AB - Primary antiphospholipid syndrome is characterized by venous and arterial thrombosis, fetal loss, or thrombocytopenia in association with antiphospholipid antibodies and no associated disease process. The authors report a case of lower extremity thrombosis in a 12 year old who had primary antiphospholipid syndrome. To our knowledge, this is the first report of peripheral arterial thrombosis in primary antiphospholipid syndrome in the pediatric population. PMID- 7877014 TI - Symptomatic brachial artery aneurysm in a child. AB - The authors present the case of a 3-year-old boy who had transient ischemic symptoms secondary to thromboembolism from a left brachial artery aneurysm not associated with trauma or an autoimmune or connective tissue disorder. He underwent emergency resection of a brachial artery aneurysm and interposition grafting. Two months later he was found to have a right brachial artery aneurysm and underwent elective aneurysm resection and interposition grafting. He was well at the 3-year follow-up and had no other arterial aneurysms. The risk of limb threat or loss can be avoided by prompt diagnosis and early surgery. The authors advocate brachial artery aneurysm resection when it becomes technically feasible and/or when thrombus is present. Patients with upper extremity aneurysms should have continuous follow-up with serial examinations to detect concomitant or subsequent aneurysm formation. PMID- 7877015 TI - Parapharyngeal teratoma in the newborn. AB - A parapharyngeal teratoma in a newborn was the cause of acute respiratory distress, which was relieved by tracheostomy. Subsequent investigations by soft tissue x-rays of the neck, computed tomography, and examination under anesthesia defined the anatomic location of the tumor, its extent, and its likely nature. The tumor was removed completely by the transcervical approach. Mandibulotomy was not required. Histological examination showed the presence of a large amount of mature brain tissue, a moderate amount of collagenous fibers and smooth muscle cells, and a minute amount of cartilage and epithelial structures. The postoperative course was satisfactory. No recurrence was seen 6 years after surgery. The computed tomography scan was found to be the most useful investigative method. To the authors' knowledge, this is the first comprehensive report of a teratoma occupying the parapharyngeal space in a newborn. PMID- 7877016 TI - Parathyroid cysts: report of the sixth and youngest pediatric case. AB - A nonfunctioning parathyroid cyst occurred in an 8-year-old girl, the youngest patient reported to have this diagnosis. Most cysts are asymptomatic; a few are associated with signs and symptoms of hyperparathyroidism. In asymptomatic patients with a lateral neck cyst, aspiration of clear fluid with an elevated parathyroid hormone level is diagnostic of a parathyroid cyst. If this results in disappearance of the cyst, without recurrence, no further treatment is necessary. If the cyst recurs, aspiration may be repeated. However, persistence of the cyst despite aspiration or recurrence after the second aspiration should prompt surgical removal, with intraoperative identification of all parathyroid glands, because functioning parathyroid cysts are associated with a high risk of hyperplasia or adenoma. PMID- 7877018 TI - Surgical repair of an aortic coarctation in a patient after treatment with extracorporeal membrane oxygenation. AB - Extracorporeal membrane oxygenation (ECMO) is a life-saving treatment for neonates who have severe respiratory failure that does not respond to maximal conventional therapy. A consequence of venoarterial ECMO is the sacrifice of the right common carotid artery. Evaluation of the impact of a single carotid artery in babies treated with ECMO concerns mostly long-term neurodevelopmental outcome. The authors encountered a peculiar problem caused by a single carotid artery in a post-ECMO patient during the surgical correction of aortic coarctation with hypoplastic distal aortic arch. For patients with a confirmed cardiac malformation that necessitates future surgical repair and for whom ECMO support is required, reconstruction of the right common carotid artery should be considered. Veno-venous ECMO is an alternative solution if this approach is not contraindicated because of the patient's clinical condition. Patients with congenital diaphragmatic hernia have a higher incidence of cardiac malformations; therefore, careful cardiological attention is required. Anomalies masked by pulmonary hypertension also must be considered. PMID- 7877017 TI - Familial childhood parathyroid adenoma. PMID- 7877019 TI - Postpericardiotomy syndrome and chylopericardium: two unusual complications after aortopexy for tracheomalacia. AB - In two boys (aged 10 years and 7 months), large symptomatic pericardial effusions developed after aortopexy for tracheomalacia. Both patients underwent percutaneous pericardial drainage. The delayed presentation (3 weeks postoperatively) and associated findings in the 10 year old were typical of postpericardiotomy syndrome, and he had an uneventful recovery after a course of aspirin therapy. The 7 month old had chylopericardium and was treated with pericardial drainage and a low-fat, medium-chain triglyceride diet. Both cases represent previously unreported complications of aortopexy. PMID- 7877020 TI - Intraoperative cardiopulmonary resuscitation in the prone position. AB - Cardiopulmonary resuscitation (CPR) occasionally is necessary in the operating room setting. In such instances, it may be difficult to perform CPR if the patient is in the prone position. Although the supine position is optimal for CPR, it may not be feasible because of the risks of damage to craniospinal structures. The authors present the case of a 12-year-old boy who had cardiac arrest during spinal fusion. Successful CPR was performed with the patient in the prone position, with the use of "reversed precordial compressions," and the patient was resuscitated despite 7 minutes of asystole. Effective cardiac output was maintained and was confirmed by systolic blood pressure readings of 80 to 90 mm Hg on both the arterial catheter waveform and the noninvasive blood pressure cuff, by a waveform and the reading on the pulse oximeter, and by the presence of end-tidal carbon dioxide. PMID- 7877021 TI - Intrapleural instillation of urokinase in the treatment of loculated pleural effusions in children. AB - The authors report on the use of intrapleural instillation of urokinase in the treatment of loculated pleural effusions in two pediatric patients. Urokinase helps to lyse fibrin by converting plasminogen to plasmin. The intrapleural instillation of urokinase is safe and effective for promoting drainage of loculated intrapleural effusions, and it proved a useful option in the treatment of persistent loculations. PMID- 7877022 TI - Pancreatic pleural effusion: an indication for emergency distal pancreatectomy and Roux-en-Y pancreatico-jejunostomy. AB - A previously healthy 2-year-old boy was admitted because of shortness of breath, cough, and fever; there was minimal abdominal pain. He had recurrent right, followed by left pleural effusions, which contained markedly elevated amylase levels and high protein content. The pleural fluid amylase levels were disproportionately higher than the serum amylase levels. His abdominal signs were minimal. Surgical exploration showed a disruption of the proximal pancreatic duct. Distal pancreatectomy and Roux-en-Y pancreatico-jejunostomy were performed. After a complicated postoperative course he was discharged well and has remained so for more than 2 years. PMID- 7877023 TI - Selective bronchial occlusion for treatment of bullous interstitial emphysema and bronchopleural fistula. AB - A preterm infant, ventilated for hyaline membrane disease, had severe right-sided pulmonary interstitial emphysema, left-sided compression atelectasis, and bronchopleural fistula. Several modalities of treatment were tried and were unsuccessful. Selective bronchial occlusion with a balloon catheter resulted in dramatic improvement in the patient's clinical and radiographic condition. PMID- 7877024 TI - Traumatic rupture of the tracheobronchial tree in a 2 year old. AB - Tracheobronchial tree injuries occur in a small number of patients after blunt chest trauma, and their occurrence is even more uncommon in the pediatric trauma population. The authors present the case of a 2-year-old boy who presented with rupture of the trachea and disruption of the right upper lobe bronchus and bronchus intermedius. PMID- 7877025 TI - Pleomorphic adenoma of the main bronchus. PMID- 7877026 TI - Pulmonary blastoma in children: report of two cases and review of the literature. AB - Pulmonary blastoma is a rare primary neoplasm of the lung. Approximately 25% of the reported cases have occurred in pediatric patients. The authors found 45 cases of these tumors in children aged < or = 16 years, and report two more cases of pulmonary blastoma--in a 3 1/2-year-old boy and a 22-month-old girl. Because these tumors are considered malignant, surgical excision is recommended. PMID- 7877027 TI - Lobar lung transplantation as a treatment for congenital diaphragmatic hernia. AB - The mortality rate for infants severely affected with congenital diaphragmatic hernia (CDH) remains high despite significant advances in surgical and neonatal intensive care including delayed repair and extracorporeal membrane oxygenation (ECMO). Because of the increasingly successful experience with single-lung transplantation in adults; this approach has been suggested as a potential treatment for CDH infants with unsalvageable pulmonary hypoplasia. The authors report on a newborn female infant who was the product of a pregnancy complicated by polyhydramnios. At birth, she was found to have a right-sided CDH and initially was treated with preoperative ECMO, followed by delayed surgical repair. Despite the CDH repair and apparent resolution of pulmonary hypertension, the infant's condition deteriorated gradually after decannulation, and escalating ventilator settings were required as well as neuromuscular paralysis and pressor support because of progressive hypoxemia and hypercarbia. A lung transplant was performed 8 days after decannulation, using the right lung obtained from a 6-week old donor. The right middle lobe was excised because of the size discrepancy between the donor and recipient. After transplantation, the patient was found to have duodenal stenosis and gastroesophageal reflux, which required duodenoduodenostomy and fundoplication. The patient was discharged from the hospital 90 days posttransplantation, at 3 1/2 months of age. Currently she is 24 months old and doing well except for poor growth. This case shows the feasibility of single-lung transplantation for infants with CDH, and the potential use of ECMO as a temporary bridge to transplantation. Lobar lung transplantation allowed for less stringent size constraints for the donor lung. PMID- 7877028 TI - Massive thymic hyperplasia: characterization of a rare mediastinal mass. AB - Thymic hyperplasia is a rare cause of an anterior mediastinal mass in children. True thymic hyperplasia is characterized by massive thymic hypertrophy with retention of normal thymic architecture, and must be distinguished from more commonly seen tumors of the anterior mediastinum. Previous reports of thymic hyperplasia primarily have been descriptive, with minimal analysis of the cellular characteristics of the tumor. To better describe the cellular characteristics of thymic hyperplasia, the authors report on a 10-year-old boy found to have an asymptomatic left paracardiac mass during cardiac evaluation. The mass enlarged rapidly during the following 2 weeks and filled the entire left side of the chest. An open biopsy specimen showed normal thymic architecture. Because of the size and rapid growth of the mass, the authors decided to resect it. Cellular analysis of the mass did not show differences from normal thymic elements. There was conserved thymic architecture. The expression of cell surface markers and the proliferative response of thymocytes to cytokines appeared to be normal. Similarly, a long-term cell culture of the thymocytes did not result in clonal proliferation. Immunohistologic staining of stromal cells showed no striking differences from normal thymic elements. Moreover, immunologic analysis of the patient by standard hematological parameters, lymphocyte subsets, quantitative immunoglobins, and immunoelectrophoresis showed no abnormalities except for lymphocytosis, which resolved after tumor resection. The authors conclude that thymic hyperplasia occurs in immunologically normal children and may exhibit (1) rapid growth with minimal associated symptoms, (2) normal thymic architecture, (3) normal thymocyte and stromal growth characteristics in vitro, and (4) a normal thymocyte response to cytokine stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877029 TI - Respiratory obstruction caused by lipoma of the esophagus. AB - A four-year-old boy presented with wheezing of 5 months' duration after a cold. During examination, an opacity was noted in the superior mediastinum, causing displacement of the trachea to the right. A barium swallow showed a mass in the wall of the esophagus, occupying the lumen, without causing any obstruction. Through further examination by computed tomography and magnetic resonance imaging, the mass was confirmed to be a lipoma in the wall of esophagus, causing displacement of trachea. The mass was removed via the transcervical approach, and the postoperative course was uneventful. Respiratory obstruction caused by a lipoma of esophagus in childhood had not been reported in the English language literature. PMID- 7877030 TI - Recurrent tracheoesophageal fistula treated with fibrin glue. AB - Recurrent tracheoesophageal fistula (RTF) after repair of esophageal atresia with tracheoesophageal fistula is a serious complication, with the need for a second operation. The mortality rate is high. The authors report on the eradication of RTF using fibrin glue. PMID- 7877031 TI - Conservative surgery for splenic hydatid cyst. AB - Splenectomy has been the treatment of choice for hydatid cyst of the spleen. By successful enucleation of a deep-seated splenic hydatid cyst and preservation of the spleen, the authors show the technical feasibility of such a procedure and recommend it as the treatment of choice. PMID- 7877032 TI - Heterotopic splenic autotransplantation for splenomegaly secondary to Gaucher's disease--a case of siblings. AB - The authors report on siblings with Gaucher's disease who underwent heterotopic splenic autotransplantation for splenomegaly. The efficacy of this treatment is discussed. PMID- 7877033 TI - Management of hemobilia and persistent biliary fistula after blunt liver trauma. AB - A 10-year-old girl had hemobilia and a biliocutaneous fistula after blunt abdominal trauma. Embolization of the right hepatic artery occluded the hepatic artery aneurysm, but the cutaneous biliary fistula persisted despite prolonged (8 months) conservative management including sphincter decompression with an endoscopically placed biliary stent. Roux-en-Y fistuloenterostomy eventually cured the bile leak. PMID- 7877034 TI - Traumatic rupture of the choledochus treated temporarily by Roux-en-Y entero hepato-duodenal ligamentostomy. AB - The authors report on a 3-year-old boy who had traumatic rupture of the choledochus. Temporary internal drainage was achieved by Roux-en-Y end-to-side entero-hepato-duodenal ligamentostomy. Two months later, a standard Roux-en-Y end to-side choledocho-jejunostomy was performed. Five years after the injury, the child is well and has no jaundice. PMID- 7877035 TI - Acute acalculous cholecystitis in an infant after cardiac surgery. AB - Acute acalculous cholecystitis is a virulent disease that occurs most commonly in critically ill patients. Imaging studies may facilitate earlier diagnosis and may decrease the morbidity and mortality rates. The authors report on a 30-month-old child with acute acalculous cholecystitis after surgical repair of tetralogy of Fallot. A review of the clinical pathogenesis, diagnosis, and treatment is included. PMID- 7877036 TI - Obliteration of the distal bile duct in the development of congenital choledochal cyst. AB - The authors report the first case of antenatally diagnosed choledochal cyst having evidence of early fetal bile drainage and complete obliteration of the distal bile duct. This disputes the traditional hypothesis of reflux of pancreatic enzymes and supports the recent theory of primary obstruction as the etiologic cause of choledochal cyst. Coexisting congenital hypothyroidism and pulmonary stenosis had not been reported previously. PMID- 7877037 TI - Common bile duct obstruction related to intestinal polyposis in a child with Peutz-Jeghers syndrome. AB - Peutz-Jeghers syndrome is characterized by hamartomatous polyposis of the small and large bowel and mucocutaneous pigmentation. The authors describe a 9-year-old girl with small bowel obstruction related to duodenal intussusception caused by polyposis in the fourth portion of the duodenum. Operative reduction of the intussusception and excision of the polyps were performed, at which time the pancreas appeared to have mild pancreatitis. A liver biopsy specimen showed mild portal fibrosis and ductal proliferation. The patient did well postoperatively, but later presented with symptoms consistent with biliary obstruction. Percutaneous transhepatic cholangiography showed pancreatic and biliary duct dilatation as well as obstruction of the common bile duct, which extended into the left upper quadrant. Exploration showed ampullary obstruction several centimeters proximal to the line of resection. Sphincteroplasty was performed. The postoperative course was uncomplicated. The authors conclude that Peutz Jeghers syndrome with polyps in the duodenum can markedly distort duodenal and ductal anatomy and can lead to ampullary obstruction. PMID- 7877038 TI - Membranous atresia of the body of the stomach. AB - Pyloric and prepyloric webs and atresias have long been recognized and frequently reported; however, membranous atresia of the body of the stomach has not been reported previously. The authors report such a case. PMID- 7877039 TI - Congenital (prepyloric) antral membrane: prenatal diagnosis and treatment. AB - Congenital antral membrane is a rare cause of gastric outlet obstruction. Symptoms can be seen in any age group, depending on the degree of obstruction caused. Treatment options are pyloroplasty with incision or excision, endoscopic dilatation or resection, and medical management. The diagnosis can be suggested from prenatal examinations, and simple surgical dilatation without pyloroplasty can be successful in managing this condition. PMID- 7877040 TI - Congenital microgastria. AB - Congenital microgastria is an extremely uncommon dysplasic condition of the newborn stomach. With only 26 well-documented accounts of this anomaly reported in the literature, its treatment and long-term outcome have not been well elucidated. Herein, the authors report on a newborn with multiple congenital anomalies who presented with severe reflux and aspiration. The workup showed congenital microgastria. The infant's diagnostic and treatment course is described. PMID- 7877041 TI - Congenital microgastria in a premature infant. AB - The authors report the case of a 1,500-g baby boy with microgastria, vascular ring, tracheoesophageal fistula (TEF), and the VATER association. Despite repair of the TEF and placement of a gastrostomy tube, he failed to thrive and had recurrent bouts of aspiration pneumonia. Gastric augmentation at 8 months of age resolved the feeding problems, and he now has a normal diet. PMID- 7877042 TI - Toothbrush ingestion by bulimics may require laparotomy. AB - Two girls accidentally swallowed their toothbrush while inducing emesis; both had bulimia. Early removal of the brush is advised to prevent complications. Endoscopic removal is the preferred method, but because of the toothbrush's geometric qualities, surgical retrieval is often required. PMID- 7877043 TI - Gastrocolic fistula in a 7 week old: a rare complication after gastric perforation. AB - There are few reports of gastrocolic fistula in infancy. Our observations on the clinical course of this condition are presented. The diagnostic possibilities and surgical procedure are discussed. PMID- 7877044 TI - Duodenal atresia: its occurrence in siblings. AB - The authors describe a case of duodenal atresia occurring in two siblings. It is possible that the third sibling also died after complications of the same malformation. This familial occurrence may support the hypothesis that this anomaly is determined by an autosomal-recessive gene. PMID- 7877045 TI - Duodenal leiomyosarcoma presenting with iron deficiency anemia. AB - Failed iron therapy warrants investigation to rule out disorders of iron absorption or intestinal blood loss. The authors report the third case of duodenal leiomyosarcoma in childhood, which presented with iron deficiency anemia. Endoscopy failed to elicit the cause of this problem. Wide surgical resection, sparing the pancreas, was possible. PMID- 7877046 TI - Management of multiple jejunoileal atresias with an intraluminal SILASTIC stent. AB - Multiple small bowel atresias present a unique challenge because maximum intestinal conservation is mandatory for survival. We recently treated a patient who had multiple atresias using a 7F SILASTIC catheter as an intraluminal stent. The catheter facilitated the completion of multiple primary anastomoses and served as a conduit for radiological evaluation and enteral feeding. The patient was a 1,860-g boy with 23 atresias of the jejunum and ileum. All stenotic segments were resected, and seven primary anastomoses were completed over the catheter. The distal 34 cm of bowel were exteriorized as a mucus fistula, with the catheter extending through to the level of the ileocecal valve. The proximal jejunal limb also was exteriorized. Eleven days later, contrast was instilled through the catheter and showed no leak or stricture. The catheter was then used for enteral nutrition and administration of the proximal jejunal effluent. Bowel continuity was reestablished after a tapering enteroplasty of the proximal jejunal limb. Parenteral nutrition was ultimately discontinued. Thirty-one months later, the patient no longer requires supplemental nutritional support. This case demonstrates the safety of multiple primary anastomoses over an exteriorized intraluminal stent. The catheter was useful in the radiological evaluation of the distal limb before it was used as an access route for enteral nutrition. PMID- 7877047 TI - The proximal mesenteric flap: a method for closing large mesenteric defects in jejunal atresia. AB - In selected patients with jejunal atresia, closure of the associated large mesenteric defect remains a technical problem. A case of jejunal atresia is reported in which a segment of dysfunctional proximal jejunum was resected and its mesentery retained, creating a flap of mesenteric tissue that was used to close a large defect. This technique allowed the closure of the mesenteric defect with a decreased chance of injury or kinking of the tenuous distal mesenteric vessels, improved orientation and stabilization of the distal bowel, and, theoretically, improved blood flow to the distal segment. PMID- 7877049 TI - Adenomyoma of the small intestine in children. AB - Two cases of adenomyoma of the small intestine occurring in two young children are described. One child presented with intussusception. In the other, the lesion was an incidental intraoperative finding. Underreporting is probably a major reason for the apparent rarity of this lesion in the small intestine. The condition should be considered a cause of small bowel intussusception. PMID- 7877048 TI - Retrograde intussusception: a lead-point for prograde intussusception. AB - Retrograde intussusception is an extremely rare entity. The authors report a case of retrograde jejuno-jejunal intussusception in a 12 year old. The features of interest are (1) the retrograde intussusception mass acting as a lead-point for a second prograde jejuno-jejunal intussusception, (2) the anastomotic suture line of a previous resection-anastomosis acting as the lead-point for the retrograde intussusception, and (3) the presence of a "reverse claw sign" (on a barium meal study) caused by the intussusceptum of the retrograde intussusception. PMID- 7877050 TI - Jejunal obstruction as a late result of neonatal jejunal atresia. AB - The authors report on two adults who had jejunal dilatation after having had resection for jejunal atresia in the neonatal period. Both patients presented 20 years after the initial procedure, with severe iron deficiency anemia, marked jejunal dilatation proximal to the old anastomotic site (which was not narrowed), and a bezoar within the dilated segment. Upper gastrointestinal series were used to evaluate both patients before surgical resection of the enlarged intestine, with subsequent correction of the anemia. PMID- 7877051 TI - Peritoneal band containing talc: rare cause of small bowel obstruction in a previously unoperated child. AB - The authors report on a 10-year-old boy who was operated on for small bowel obstruction. The obstruction was caused by a peritoneal band that was found to contain talc of an unknown source. The possible explanation for this rare pathology is discussed. PMID- 7877052 TI - Lead intoxication from a pellet entrapped in the appendix of a child: treatment considerations. AB - A 4-year-old boy with symptoms of lead intoxication and confirmatory serum lead levels was eventually found to have a pellet lodged in his appendix. Because laxatives and cathartics did not dislodge the pellet, appendectomy was performed. Arguments for and against this decision are explored. PMID- 7877053 TI - Yersinia pseudotuberculosis affecting the appendix. AB - Yersinia pseudotuberculosis is an uncommon cause of abdominal pain. It has a much lower incidence than Yersinia enterocolitica, and most reports have emanated from Europe or North America. This report is about a patient with Yersiniosis affecting the appendix alone, in contrast to the usual picture of mesenteric adenitis or septicemia associated with this organism. PMID- 7877054 TI - An unusual complication of appendectomy. AB - Intraabdominal abscess formation is a well-recognized complication of perforated appendicitis. Extraabdominal complications, however, are rare. The authors present the case of an 8-year-old boy who had an acute painful right-sided scrotal mass 2 days after an operation for perforated appendicitis. During exploration, an abscess within a previously undiagnosed patent processus vaginalis was found and successfully managed by drainage. This case demonstrates that a persistent patent processus vaginalis may predispose to scrotal pathology secondary to intraabdominal sepsis and represents a unique complication of perforated appendicitis. PMID- 7877055 TI - Thoracic empyema in a patient with acute appendicitis: a rare association. AB - Thoracic empyema and appendicitis rarely are concomitant. This is the first report of ultrasonography and computed tomography being used preoperatively to establish the diagnosis of ruptured appendicitis in a child with thoracic empyema. The perforated appendicitis was identified after gastrointestinal flora were cultured from the thoracostomy drainage of the empyema. PMID- 7877056 TI - Posterior hepatodiaphragmatic interposition of the colon complicated by appendicitis. AB - Posterior hepatodiaphragmatic interposition is a rare malposition of the cecum that persists over time but is usually of little or no clinical importance. However, when inflammation occurs in the appendix, the symptoms and signs are those of subphrenic disease rather than abdominal disease and may be misleading to the attending physicians. Radiologists should report the presence of anterior and posterior hepatodiaphragmatic interposition and should differentiate between the two. PMID- 7877057 TI - Colonic hyperganglionosis presenting as neonatal enterocolitis and multiple strictures. AB - Neuronal intestinal dysplasia (NID) usually mimics Hirschsprung's disease, but rarely presents as neonatal enterocolitis. The authors report a case of colonic hyperganglionosis, which is a form of NID, presenting with postenterocolitis intestinal strictures. NID should be considered as a possible (although rare) cause of neonatal enterocolitis and may present with intestinal strictures. PMID- 7877058 TI - Primary chemotherapy for children with rhabdomyosarcoma of the "special pelvic" sites: is preservation of the bladder possible? PMID- 7877059 TI - Further evidence for surfactant deficiency in CDH. PMID- 7877060 TI - Case report of a left-sided gastroschisis. PMID- 7877061 TI - A 40-week-gestational-age, 2.5-kg girl with a prenatally diagnosed giant omphalocele was delivered by elective cesarean section. PMID- 7877062 TI - Familial gastroschisis in siblings is rare. PMID- 7877063 TI - Mast cells in the placenta. Is there a relation to the development of atopic disease in infants before 18 months of age? AB - OBJECTIVE: To disclose a relation between the amount of mast cells in placenta and the development of atopic disease in children before 18 months of age. DESIGN: A prospective, descriptive study. SETTING: Two obstetric departments at university hospitals. SUBJECTS: 67 pairs of mothers and their newborn infants. MAIN OUTCOME MEASURES: Family history of atopic disease was taken. The amount of mast cells in placenta was counted. Follow-up questionnaires of the children were evaluated after 18 months. RESULTS: The follow-up rate was 84%. The number of mast cells in placenta did not differ between atopic and non-atopic children. CONCLUSION: A new predictor, the amount of mast cells in placenta was evaluated. In this study the amount of mast cells, in placenta was not predictive of the development of atopic disease before 18 months of age. PMID- 7877064 TI - Fetal anomalies in a controlled one-stage ultrasound screening trial. A report from the Helsinki Ultrasound Trial. AB - The aim of the study was to compare whether systematic strictly timed screening of all pregnancies would improve the detection of major fetal anomalies. All pregnant women (95%) from a certain area were randomly allocated for one ultrasound screening examination between the 16th and 20th weeks of gestation. Otherwise the screening (N = 4691) and control groups (N = 4619) received the same antenatal care. Screening included a systematic search for fetal anomalies. In the screening group, 40% of major fetal anomalies were detected in the screening, and 11 abortions were induced because the malformation was either lethal or severely handicapping. In the control group, 77.0% of participants had ultrasound examination any time during pregnancy. By ultrasound 13 (27%) major fetal anomalies were detected, only two of these before the 21st week of gestation. Screening detected most of the anomalies of the central nervous system and genitourinary system and cases with multiple anomalies, but was less satisfactory in detecting the anomalies of the heart and gastrointestinal tract. The perinatal mortality rate was 4.2 per 1000 in the screening group and 8.4 per 1000 in the control group (p = 0.013). The detection of major fetal anomalies in ultrasound screening can reduce perinatal mortality. A systematic search for fetal anomalies should be included in the ultrasound screening of all pregnancies. PMID- 7877065 TI - Transcranial assessment of maternal cerebral blood flow velocity in normal VS pre eclamptic women (variation with maternal posture). A preliminary study. AB - To compare the effect of a change in maternal posture on maternal cerebral blood flow velocity assessed transcranially in a normal vs a pre-eclamptic group 5 normotensive and 5 pre-eclamptic patients had maternal middle cerebral artery (MCA) blood flow velocity assessed in 2 positions supine and sitting upright using a 2 mHz transcranial doppler ultrasound. Comparison was then made of the effect of a change in posture on cerebral blood flow velocity in both groups using paired student-t test. Normotensive women showed minimal change in MCA blood flow velocity while pre-eclamptic women showed a 20% rise in all aspects of MCA blood flow velocity from supine to sitting. In pre-eclamptic patients MCA blood flow velocity which showed a significant rise with change in posture is not accompanied by significant changes in blood pressure and so is not a secondary response to a change in cardiac output by may be a primary effect related to local circulatory changes. Transcranial assessment of maternal cerebral blood flow velocity performed in normotensive and various hypertensive groups showed significant variation with change in posture in the pre-eclamptic group. PMID- 7877066 TI - Clinical value of antenatal fetal pulse oximetry. AB - The aim of this prospective observational study was to see if high quality fetal pulse oximetry signals can be obtained from the fetus before labour. It was carried out in Labour Ward, Clarendon Wing, Leeds General Infirmary and St. James Hospital, Leeds. We studied Caucasian term fetuses antenatally and 20 fetuses during labour. Antenatal fetal oxygen saturation was measured using a sensor passed through the cervix onto the membranes covering the fetus before the onset of labour. The quality of these signals was compared to data obtained from 20 fetuses monitored during active labour after amniotomy. High quality pulse oximetry signals were obtained for less than 1% of the monitoring time before the onset of labour (95% CI 0-2.5%). High quality data was seen 38.6% of the time once the membranes were ruptured and the head descendend into the pelvis. With present technology fetal pulse oximetry will not contribute to antenatal fetal assessment. PMID- 7877067 TI - Does a paracervical block with bupivacaine change vascular resistance in uterine and umbilical arteries? AB - Paracervical block during labor following normal, uncomplicated pregnancy is occasionally accompanied by fetal bradycardia. To evaluate whether a paracervical block with bupivacaine causes changes in the vascular resistance of uteroplacental and umbilicoplacental blood flow, a total of 12 singleton, uncomplicated pregnancies in active labor at the end of pregnancy were included to this study. By using pulsed color Doppler ultrasound techniques the pulsatility indices were measured from both uterine and umbilical arteries before, one minute and 20 minutes after a paracervical block with bupivacaine. Pulsatility indices of both uterine and umbilical arteries remained unchanged throughout the study period, as did fetal and maternal heart rates. In two cases fetal bradycardia developed, causing a marked increase in the vascular resistance of the umbilical artery one minute after the paracervical block. In the uterine arteries there was only a minor increase. When the fetal bradycardia ceased the pulsatility indices returned to the levels at the beginning of the study. Paracervical block with bupivacaine in normal pregnancies without signs of chronic or acute fetal distress does not change the vascular resistance in the uterine or umbilical arteries. If fetal bradycardia develops, it seems to be due to the direct effect of bupivacaine on the fetus, mainly on the umbilical vessels. PMID- 7877068 TI - Histometric investigations of placental villi in cases of unexpected fetal acidosis. AB - It is not unusual that, after an apparently uneventful pregnancy and birth, postpartal analysis of fetal blood unexpectedly reveals the presence of peripartal acidosis, a finding that is inexplicable on the basis of routine observation of the placenta. Using computer-assisted histometric procedures, it is possible to make a quantitative assessment with respect to the maturity and differentiation of villi, thus casting light on the functional anatomy of these structures. 89 single-birth pregnancies were grouped in accordance to the pH of blood in the umbilical artery (pre-acidosis, acidosis, non acidotic). In acidotic newborns, there is an absolute reduction in the surface area of the placenta available for fetomaternal metabolic exchange as well as a reduced surface/weight ratio largely attributable to the significantly reduced villous density. These changes lead to a compensatory increase of epithelial plates on the surface of villi and also causes a decrease in the fetomaternal diffusion distance. The application of a modern computer-assisted structural analysis helps toward clarifying the diagnosis. PMID- 7877069 TI - Antenatal betamethasone-dose-effects on fetal rat lung morphology and surfactant. AB - Pregnant rats received betamethasone 0.02, 0.05, 0.10, or 0.20 mg/kg body weight/day or saline (controls) for three days before delivery of fetuses at day 19 of gestation. Dose related effects on morphology, dipalmitoyl phosphatidylcholine content, and phosphatidylcholine species composition of the fetal lungs were evaluated. Injection of 0.02 and 0.05 mg/kg body weight betamethasone resulted in cellular differentiation of some cells, but the increase in dipalmitoyl phosphatidylcholine content was not significant. Dosages of either 0.10 or 0.20 mg/kg body weight resulted in markedly accelerated organ differentiation, complete cytodifferentiation of type II cells, and markedly increased numbers of lamellar bodies per alveolar type II cell. Compared to the controls, maternal administration of 0.10 or 0.20 mg/kg betamethasone caused significant increases of both fetal lung dipalmitoyl phosphatidylcholine content, and the fraction of dipalmitoyl phosphatidylcholine of total phosphatidylcholine. None of the parameters differed between the groups that were treated with 0.10 or 0.20 mg/kg body weight betamethasone respectively. Diminution of lung DNA content was significant after treatment with betamethasone in doses of 0.05, 0.10, and 0.20 mg/kg body weight. The results of the present study suggest that maternal treatment with lower doses than those in common usage may be successful in prevention of respiratory distress syndrome, and that higher dosages do not confer any additional advantage. PMID- 7877070 TI - Intrauterine growth retardation: fluctuation of fetal pH measured between beginning and at the completion of labor. AB - The aim of this study was to evaluate the fluctuation of fetal pH in blood samples taken at the beginning of labor and at the moment of birth as related to intrauterine growth retardation syndrome. This is a prospective follow-up of term gestations, of which 41 were diagnosed as intrauterine growth retardation (IUGR) and 61 as normal ones. pH was measured in scalp blood sample at the beginning of the labor and in umbilical artery right after birth in both groups respectively. The rate of decrease of pH value in relation to duration of labor was determined for each case. Our results are: 1) Lower baseline pH were found in the IUGR group (pH 7.32 vs 7.34, p < 0.01), lower arterial blood pH at birth/.23 +/- 0.08 vs 7.27 +/- 0.08, p < 0.05). 2) Faster decrease of the pH during the labor (0.019 unit/hour vs 0.012, p < 0.05) as related to IUGR. CONCLUSION: IUGR fetuses are more acidotic at the beginning of the labor, and the rate of decrease of the fetal pH per unit of time during the labor is faster at least in a theoretical situation nevertheless it will require more studies if any practical applications are thought of. PMID- 7877071 TI - Blue fish intake and percentual levels of polyunsaturated plasmatic fatty acids at labor in the mother and the newborn infant. AB - To assess the relationship between maternal blue fish intake during pregnancy and n-3 and n-6 polyunsaturated fatty acid percentual levels in the mother and the newborn infant. Retrospective dietetic investigation at labor regarding fatty fish intake and blind plasma fatty acid analysis. Patients participants: 35 mothers and their newborn infants were studied in the Academic tertiary hospital. Mothers were classified in "blue fish high intake" group (blue fish intake > 35 g/day), intermediate intake group (12-35 g/day) and low intake group (< 12 g/day). Eleven fatty acids were analysed in plasma by means of gas chromatography. Percentual arachidonic acid levels were lower in "blue fish high intake" group mothers. Regarding the newborn infants, no differences were found concerning maternal intake. In the "intermediate intake" group of mothers, a correlation was found for maternal and fetal levels in the following fatty acids: myristic, linoleic and linolenic acids, as well as in the sum of n-6 fatty acids. Although blue fish intake influences maternal plasma levels of arachidonic acid, it does not play a decisive role in either maternal or fetal eicosapentaenoic or docosahexaenoic acid levels. Other factors need to be considered such as n-6/n-3 metabolic interaction, other nutrient composition and especially the role of placenta and fetal liver in the metabolism of polyunsaturated fatty acids. PMID- 7877072 TI - Preliminary evaluation of an intelligent system for the management of labour. AB - Over the past 10-15 years, workers using conventional computing approaches have attempted to provide an accurate assessment of fetal condition during labour based on the cardiotocogram (CTG) alone. These have not proved successful perhaps because the correct interpretation of fetal condition also requires physiological knowledge, specific patient information, knowledge of events during labour and considerable practical experience. An intelligent system which considers all the relevant information and embodies expertise may better diagnose fetal condition and support decision making. This study reports the preliminary evaluation of such a system and investigates whether this approach can attain a performance comparable with experienced local clinicians. From a database of 200 high risk labour records, 30 cases were selected; the 9 cases which received clinical intervention for 'fetal-distress' and a further 21 cases selected randomly. The management specified by the system, 3 experienced clinicians (A, B and C) and the actual clinical management were compared in a retrospective blinded review. The experts were found to agree well with each other. Expert A reviewed the cases five months later and was found to be entirely consistent in the management of 28 of the 30 cases. The system's actions were indistinguishable from the experts' and in no case did the system recommend an action not also recommended by at least one experienced reviewer. This study demonstrates the potential of an intelligent system to assist in the management of labour. PMID- 7877073 TI - Outcome of pregnancies associated with marked gestational thrombocytopenia. AB - The purpose of this prospective study was to investigate the outcome of pregnancies associated with marked gestational thrombocytopenias (< 100,000/mm3) including postpartum resolution and neonatal influence. Over a period of 18 months, 20 cases of thrombocytopenia were observed; of them 19 were diagnosed as gestational thrombocytopenia with platelet values of < 100,000/mm3. Fifteen women returned to a normal platelet count within two weeks after delivery and four within four weeks. No cases of thrombocytopenia were found among the infants and no cases of coagulation disturbance were observed in the mothers at delivery or in the postpartum period. The findings of the present study indicate that in cases of gestational thrombocytopenia, apart from a careful maternal and fetal surveillance, no intervention is necessary during pregnancy or delivery if there is no obstetrical indication. PMID- 7877074 TI - Evidence for the existence of intraepithelial nerve endings in the junctional epithelium of rat molars: an immunohistochemical study using protein gene product 9.5 (PGP 9.5) antibody. AB - Innervation of the junctional epithelium was investigated in rat molars by means of immunohistochemistry for protein gene product 9.5 (PGP 9.5) at light and electron microscopic levels. In comparison with our previous study on same tissues using neurofilament protein (NFP)-antibody, the PGP 9.5-immunostaining further disclosed numerous nerve fibers in the gingiva of rat molars and revealed the existence of a well-developed plexus of PGP 9.5-positive nerve fibers. The interproximal portion also contained numerous nerve fibers. Observation of horizontal sections revealed a denser innervation toward the inner junctional gingival epithelium than the outer marginal epithelium. The nerve fibers, beaded in appearance and extending from the nerve bundles in the lamina propria, penetrated into the junctional epithelial layer and were distributed throughout the junctional epithelium, with some nerves being located near the epithelial surface. Non-neuronal cells showing PGP 9.5-immunoreactivity were absent in the junctional epithelium. In immunoelectron microscopy, the axoplasm of nerves in the gingiva was filled with electron-dense reaction products of PGP 9.5, except for the cell organellae. The nerve fibers were devoid of Schwann cell investment and terminated among the epithelial cells in the junctional epithelium, frequently beneath the epithelial surface. The intraepithelial nerve endings contained various kinds of vesicles including large-cored ones, supporting the presence of peptidergic innervation shown by previous studies. These findings confirmed the usefulness of PGP 9.5-immunohistochemistry for the identification of delicated nerve fibers in dental tissue, and suggested the dense network of nerve fibers that may serve as sensory receptor and other functions in the junctional epithelium. PMID- 7877075 TI - Effect of long-term methotrexate-induced neutropenia on experimental periodontal lesion in rats. AB - The effects of long-term methotrexate (MTX)-induced neutropenia on the periodontal lesion in rats were investigated histologically, histometrically and bacteriologically. A nylon thread was inserted into the interdental gingiva between the 1st and 2nd right maxillary molars of the animals 3 weeks before an application of MTX. The animals were then divided into Groups A and B. Group B were injected intraperitoneally with 1.0 mg/kg of MTX 3 times per week for 9 weeks. Group A received saline as a control. Five animals were killed at the 1st, 3rd, 5th, 7th, and 9th week. In Group A, the neutrophils did not decrease during these 9 weeks. In Group B, however, the neutrophils decreased during the 3rd to 9th week. Whereas the experimental side of Group A showed only moderate alveolar bone resorption between the 7th and 9th week, [in Group B] a marked alveolar bone resorption occurred in Group B occurred in the same period. Alveolar bone loss in the experimental side of Group B was significantly greater (p < 0.01) than in Group A in the 7th to 9th weeks. The percentage of gram-negative rods increased in both control and experimental sides of Group at the 9th week. The results of the present study indicate that neutropenia is induced by a long-term application of MTX in rats and that alveolar bone destruction increases as time goes by in the area where a nylon thread was inserted. PMID- 7877076 TI - Altered collagen metabolism in nifedipine-induced gingival overgrowth. AB - Fibroblasts from nifedipine-induced fibrotic gingiva (NFG) have been characterized with respect to several cellular functions which could contribute to the characteristic clinical overgrowth of the gingiva: collagen synthesis and breakdown, glycosaminoglycan production, fibronectin synthesis, and proliferation. Histologic examination of NFG tissue revealed a hyperplastic epithelium with elongated, branched rete pegs. The connective tissue consisted of densely-packed collagen fibers and numerous enlarged fibroblasts, as well as regions of thinner, disorganized collagen fibers in the vicinity of scattered inflammatory and mast cells. Results of in vitro experiments showed that the fibroblast strains from the fibrotic gingiva (NFG) produced significantly greater amounts of collagen and lower levels of collagenase activity when compared to age and sex-matched normal human gingival fibroblast strains. The NFG fibroblasts did not produce significantly greater amounts of fibronectin, and their level of glycosaminoglycan production was less than that of the normal fibroblasts. The NFG fibroblasts did not proliferate significantly more rapidly than the normal fibroblast strains. These findings therefore show that there are defects in the regulation of collagen production by NFG fibroblasts in vitro, and suggest that these alterations in collagen metabolism contribute to the over-deposition of collagen in this tissue, rather than hyperproliferation of the fibroblasts or through the production of increased amounts of fibronectin and glycosaminoglycans. PMID- 7877077 TI - Scanning electron microscopy of Eikenella corrodens colony morphology variants. AB - Eikenella corrodens is a gram-negative, human pathogen which exhibits colony morphology variation. Scanning electron microscopy (SEM) was used to examine large (non-corroding) and small (corroding) colony variants from the type strain (ATCC 23834) and two clinical isolates (strains VA1 and CM1). Large colonies were large, flatter, and appeared relatively featureless compared to small colonies and had even, smooth colony margins. Small colonies were more raised from the medium surface, and often had a central raised region surrounded by flatter border. Cells on the surface of large colonies were more regularly arranged at the colony edge, and end-to-end rows of cells around the colony were seen in some strains. Cells in the center of the upper surface of small colonies were usually randomly arranged. Within cross sections of small colonies, cells were arranged randomly or perpendicular to the medium; in large colonies, cells were random or arranged horizontally. Amorphous, "slime" material was often seen covering groups of cells in large and small variants. An unusual variant, possibly a mutant, which combined features of both colony types was isolated. PMID- 7877078 TI - Interleukin-1 beta stimulates collagenase production by cultured human periodontal ligament fibroblasts. AB - To examine the effects of interleukin-1 beta (IL-1 beta) on collagenase production by human periodontal ligament fibroblasts (PLF) and gingival fibroblasts (GF) in culture, collagenase activity in conditioned media was determined using a novel procedure that circumvented interference by enzyme inhibitors. Fibroblasts obtained from five paired periodontal ligament and gingival tissues were cultured for two weeks, and then incubated for a further 72 h in alpha-MEM supplemented with various concentrations of IL-1 beta (0 to 1250 pg/ml). The conditioned media from individual cultures were harvested and treated with dithiothreitol to inactivate TIMPs, and then with APMA, to activate the latent collagenase. Collagenase activity was measured fluorometrically using FITC collagen as a substrate. IL-1 beta induced a approximately 2.4 to 5.2-fold increase in collagenase activity in PLF compared to a approximately 1.4 to 2.2 fold increase in GF. These results are in contrast to previous studies in which collagenase activity was measured in the presence of TIMPs, and indicate that PLF are more sensitive to IL-1 beta than GF. Since both PLF and GF are present in periodontal lesions, it is possible that collagenase secretion stimulated by exposure to inflammatory cell products such as IL-1 beta may participate in the destruction of collagen fibers involved in periodontal attachment. PMID- 7877079 TI - Prostaglandin E2 and interleukin-1 levels in smokeless tobacco-induced oral mucosal lesions. AB - Inflammatory mediators released as a result of smokeless tobacco (ST)-induced irritation may play a role in the development of oral mucosal lesions at habitual tobacco placement sites in ST users. The present study examined levels of interleukin-1 (IL-1) and prostaglandin E2 (PGE2) in ST-induced mucosal lesions and compared these to mediator levels in clinically normal mucosa. Soft tissue biopsies were obtained from white mucosal lesions at habitual placement sites and normal alveolar mucosal tissue at non-placement sites in 18 ST users. Fifteen non tobacco using subjects also provided normal alveolar mucosal biopsies. IL-1 and PGE2 were recovered from the specimens, and mediator levels were determined by enzyme immunoassay. Prostaglandin E2 levels (pg/mg) were lower in both regions in the ST subjects, but values did not vary significantly between the regions with 2.77 +/- 0.72 and 2.86 +/- 0.99 at placement and non-placement sites, respectively, in ST users and 7.31 +/- 3.84 in non-tobacco users. Both IL-1 alpha and IL-1 beta (pg/mg) were significantly (p < 0.01) elevated in ST lesions (IL-1 alpha = 25.56 +/- 4.00; IL-1 beta = 7.76 +/- 1.68) compared to either non placement sites in ST users (IL-1 alpha = 14.64 +/- 2.65; IL-1 beta = 1.63 +/- 0.72) or non-tobacco users (IL-1 alpha = 12.84 +/- 2.60; IL-1 beta = 2.04 +/- 0.75). In view of IL-1's role in keratinocyte proliferation and its inflammatory effects, this cytokine may contribute to mucosal and gingival alterations observed in ST users. PMID- 7877080 TI - Bone morphogenetic proteins induce periodontal regeneration in the baboon (Papio ursinus) PMID- 7877081 TI - In vitro studies on laser scaling of subgingival calculus with an erbium:YAG laser. AB - The effectiveness of a newly-developed Er:YAG laser with a fiber delivery system to remove subgingival calculus was examined in vitro. Fifty-three (53) periodontally-involved human extracted teeth with a band of subgingival calculus were used. Two experiments were conducted: in experiment 1, laser scaling was performed with water irrigation on a straight line and on a broad area, against the subgingival calculus at the energy levels of 10 to 120 mJ/pulse (3.5 to 42.4 J/cm2/pulse) and the pulse repetition rate of 10 pps. The morphological changes of the laser-scaled site were observed by SEM, and the efficiency of laser scaling was determined. In experiment 2, laser scaling was performed with and without water irrigation at 30 mJ/pulse and 10 pps. The morphological changes, the efficiencies, and temperature changes with and without water irrigation were compared. The pulsed Er:YAG laser used with water irrigation was able to remove the subgingival calculus from the tooth root effectively at the energy level of about 30 mJ/pulse (energy density: 10.6 J/cm2/pulse) and 10 pps, under in vitro conditions. Ablation of the tooth substance on laser scaling was generally observed within the cementum. There was little increase in temperature on the root surface during laser scaling. This study suggests the potential for the clinical application of the Er:YAG laser in subgingival scaling. PMID- 7877082 TI - Controlled clinical evaluation of the subpedicle connective tissue graft for the coverage of gingival recession. AB - The purpose of this study was to clinically evaluate the 1-year coverage of gingival recessions by a subpedicle connective tissue graft according to the original technique compared to untreated recessions by measuring probing sulcus depth (PSD), height of keratinized tissue (HKT), and mucogingival junction location changes. Paired gingival recessions were selected in 15 patients. In each patient, one recession was randomly assigned for treatment (test group) and the other recession was left untreated (control group) for 1 year. Surgery consisted of a connective tissue graft covered by a double papilla full thickness flap. Height of recession (HR), PSD, HKT, and cemento-enamel junction to mucogingival junction distance (CEJ-MGJ) were recorded with a calibrated probe before surgery and 1 year postoperatively. The control group showed no statistically significant differences in any of the parameters. In the test group, HR mean decreased significantly (P < 0.0006) from 3.66 mm to 1.09 mm, representing a mean root coverage of 70.5%. HKT mean increased significantly (P < 0.0006) from 1.60 mm to 4.30 mm, and PSD mean showed no statistical difference. CEJ-MGJ remained statistically unchanged. The subpedicle connective tissue graft may provide a good amount of root coverage and a substantial increase of keratinized tissue. Connective tissue grafted beneath the alveolar mucosa does not induce its transformation into keratinized gingival tissue. PMID- 7877083 TI - Prostaglandin E2 inhibits interleukin-6 release but not its transcription in human gingival fibroblasts stimulated with interleukin-1 beta or tumor necrosis factor-alpha. AB - Inflammatory mediators produced by human gingival fibroblasts (HGF) have been implicated in the initiation and progression of periodontal disease. The purpose of this study was to examine whether prostaglandin E2 (PGE2), which is produced in abundance from HGF after stimulation with interleukin (IL)-1 beta or tumor necrosis factor-alpha (TNF-alpha), could regulate IL-6 production by HGF. HGF stimulated with either IL-1 beta or TNF-alpha showed a rapid and dose-dependent increase in IL-6 mRNA accumulation and IL-6 secretion, as demonstrated by reverse transcription-polymerase chain reaction analysis and bioassay. IL-6 secretion from either IL-1 beta- or TNF-alpha-stimulated HGF was enhanced by the inhibition of PGE2 synthesis with indomethacin. Furthermore, the addition of PGE2 inhibited IL-6 secretion from these cells. In contrast, indomethacin or PGE2 did not affect the accumulation of IL-6 mRNA in IL-1 beta-stimulated HGF. These data indicate that IL-6 production by HGF is up-regulated by specific cytokines, IL-1 beta and TNF-alpha, and suggest that this production may be partially down-regulated by endogenous and exogenous PGE2 at the post-transcriptional level. PMID- 7877084 TI - A comparison of demineralized freeze-dried bone and autologous bone to induce bone formation in human extraction sockets. AB - The purpose of this study was to test the bone-forming capacity of demineralized freeze-dried bone (DFDBA) and autologous bone grafts in extraction sockets. Seven paired sites were grafted with either DFDBA or autologous bone. The sites were reentered between 3 and 13 months for the purposes of obtaining biopsies of the grafted sites and to place endosseous implants. Biopsies from 6 of the 7 grafted sites were evaluated for new bone formation. DFDBA sites revealed the presence of dead particles of DFDBA with no evidence of bone formation on the surfaces of the implanted particles and no evidence of osteoclastic resorption of the bone particles. Biopsies from the 6 autologous sites revealed vascular channels with woven and lamellar bone. Some specimens had retained cortical, non-vital bone chips. These bone chips were undergoing active osteoclastic resorption. The results of this study questions the use of DFDBA as a bone inductive graft material. PMID- 7877085 TI - Osteoporosis: a risk factor in periodontal disease. AB - Osteoporosis is suspected as a risk factor in periodontal disease, but previous studies have failed to establish a relationship. Possible explanations for this could be lack of precise methods for assessment of osteoporosis in the jaws and confounding of the result by other factors such as age, gender, or smoking. In the present study 12 female patients with osteoporotic fractures (Group O) and 14 normal women (Group N) were examined clinically for plaque (VPI), gingival bleeding (GBI), and loss of attachment on the 6 Ramfjord index teeth. Bone mineral content (BMC) of the mandible and forearm was determined by dual photon scanning. Results were presented as arithmetic means +/- standard error, and differences between groups were tested by 2-sample t-test. The two groups were comparable with respect to age (O: 68.3 +/- 1.8 years, N: 68.1 +/- 1.5 years), menopausal age (O: 47.5 +/- 1.8 years, N: 47.2 +/- 1.3 years), and smoking habits (O: 4 smokers, N: 3 smokers). The osteoporotic women had significantly lower BMC values than controls in the mandible (O: 0.63 +/- 0.04 in U/cm2; N: 0.78 +/- 0.02 in U/cm2, P < 0.01) and forearm (O: 1.05 +/- 0.05 in U/cm; N: 1.28 +/- 0.05 in U/cm, P < 0.01). No significant differences were found with respect to plaque (O: 46.67 +/- 10.00%, N: 36.67 +/- 6.67%) and gingival bleeding (O: 46.67 +/- 11.67%, N: 43.33 +/- 10.00%), whereas significantly greater loss of attachment was seen in osteoporotic women (O: 3.65 +/- 0.18 mm, N: 2.86 +/- 0.19 mm, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877086 TI - Cystinosis and gingival hyperplasia: demonstration of cystine crystals in gingival tissue and unusual aspects of management. AB - A patient with nephropathic cystinosis developed gingival hyperplasia secondary to cyclosporine-A therapy for his renal allograft. The typical crystals described on electron microscopic examination of other organs of patients with cystinosis were seen in the resected gingiva of this patient. These crystals have not been previously described in this location. Unusual aspects of the management of this patient are discussed. PMID- 7877087 TI - Non-human primate models for testing the efficacy and safety of periodontal regeneration procedures. AB - Experimentally-produced defects in the non-human primate are preferred for testing the efficacy and safety of periodontal regenerative therapies. These animals closely resemble the human in dental anatomy and periodontal wound healing physiology. Defects can be produced which do not display spontaneous regeneration and which are contralaterally identical. Thus, within animals, untreated controls can be obtained to indicate the level of supporting tissues prior to therapy. The use of non-human primate models is recommended for science transfer experiments involving invasive surgery and the testing of potentially harmful new devices and pharmaceuticals. PMID- 7877088 TI - Periodontal repair in dogs: supraalveolar defect models for evaluation of safety and efficacy of periodontal reconstructive therapy. AB - It is increasingly evident that controlled preclinical models with reproducible defect characteristics and biologic reaction are critical for evaluation of safety and efficacy of periodontal reconstructive protocols. Our investigations have characterized a supraalveolar periodontal defect in the mandibular premolar region in the beagle dog. This surgically-created critical size defect heals with almost complete connective tissue attachment following immediate reconstructive surgery. When the defect is exposed to periodontitis-simulating conditions prior to surgery the new connective tissue attachment is reduced. Bone and cementum regeneration is limited for both defect variations. Critical aspects relative to animal selection and management, surgical protocol, histologic and statistical analysis are discussed. This preclinical model has proven effective for evaluation of safety and efficacy of devices and biologics used adjunctive to periodontal reconstructive therapy. PMID- 7877089 TI - Comparison of canine and non-human primate animal models for periodontal regenerative therapy: results following a single administration of PDGF/IGF-I. AB - Two commonly used animal models for evaluating putative periodontal regenerative therapies are the beagle dog model with natural periodontal disease and the non human primate with ligature-induced attachment loss. The host response, microbiology, and skeletal rates of remodeling of these two models are summarized. In addition, the results of experiments comparing the healing response to periodontal surgery with and without concurrent use of the combination of platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) in these models are presented. At 1 month, PDGF/IGF-I administration resulted in a 64.1% and 51.4% increase in new attachment formation in the non-human primate and canine, respectively, while controls (surgery plus placebo) demonstrated 34.1% and 8.6% increases in new attachment formation in the non-human primate and canine models, respectively. Further, application of PDGF/IGF-I stimulated 21.6% and 65% osseous defect fill in the non-human primate and canine, respectively, while controls demonstrated 8.5% and 14.5% osseous defect fill in the non-human primate and canine, respectively. The osseous response in the canine appears greater than that of the non-human primate, and the new attachment formation was more substantial in the non-human primate than the canine. However, in general these data demonstrate a high degree of consistency in the effects of PDGF/IGF-I in promoting periodontal regeneration. Positive results in these two models--the dog with natural periodontal disease and the non-human primate with ligature-induced attachment loss--justify human clinical trial testing of a putative regenerative therapy. PMID- 7877090 TI - Discussion: animal models in reconstructive therapy. AB - Experimentation in animal models has created a basis for highly improved therapeutic procedures in reconstructive periodontal surgery. This symposium has discussed several animal models currently used; additional models have been described in recent literature. The presentations by Drs. Caton, Wikesjo, and Lynch illustrated the need for further discussion of some of the problems inherent in animal experimentation, including: standardization of periodontal defect configuration; adequate recording of preoperative attachment level; minimizing the effect of biological variability; use of surgically-created versus naturally-developed periodontal lesions; choice of observation period; and regenerative potential of the model chosen. PMID- 7877091 TI - Personality Assessment Inventory scale characteristics and factor structure in the assessment of alcohol dependency. AB - Individual scale characteristics and the inventory structure of the Personality Assessment Inventory (PAI; Morey, 1991) were examined by conducting internal consistency and factor analyses of item and scale score data from a large group (N = 301) of alcohol-dependent patients. Alpha coefficients, mean inter-item correlations, and corrected item-total scale correlations for the sample paralleled values reported by Morey for a large clinical sample. Minor differences in the scale factor structure of the inventory from Morey's clinical sample were found. Overall, the findings support the use of the PAI in the assessment of personality and psychopathology of alcohol-dependent patients. PMID- 7877092 TI - Defense mechanisms and personality disorders: an empirical test of Millon's theory. AB - The purpose of this study was to investigate Millon's hypothesized relationships between particular personality disorders and specific defense mechanisms. One hundred thirty psychiatric inpatients and outpatients, all diagnosed with an Axis II personality disorder, completed the Millon Clinical Multiaxial Inventory-II (MCMI-II; Millon, 1987) and the Defense Mechanism Inventory (DMI; Ihilevich & Gleser, 1986). Analyses revealed strong corroborating evidence for a number of the hypothesized relationships, including significant correlations between antisocial traits and acting out, obsessive-compulsive traits and reaction formation, paranoid traits and projection, passive-aggressive traits and displacement, and self-defeating traits and devaluation. There was also a trend suggesting the presence of a relationship between dependent personality traits and introjection. A factor analysis was also performed that suggested that method variance may be responsible for either lowered correlations between the MCMI-II and DMI or lack of significance for some predicted relationships. Results are discussed in terms of existing theory and research, and implications for treatment and future research are briefly addressed. PMID- 7877093 TI - Use of the Rotter Incomplete Sentences Blank with adolescent populations: implications for determining maladjustment. AB - Three hundred sixty-eight high school students and 136 college students were administered the Rotter Incomplete Sentences Blank (RISB; Rotter & Rafferty, 1950) and the Maudsley Personality Inventory (MPI; Eysenck, 1962). Scores on the RISB and MPI were compared to scores for the normative samples published in each test's manual. Using the RISB manual scoring criteria, over half of high school students (55%) and over 40% of college students scored above the RISB cutting score, signifying "maladjustment." Reasons for this high proportion of adolescents scoring in the maladjusted range include the fact that the RISB was normed on a college student sample from the late 1940s and the fact that the manual has never been updated. These results indicate that extreme caution should be exercised when using the RISB with adolescent populations. In addition, suggestions are made for revisions to the RISB and raising of the maladjustment cutting score. PMID- 7877094 TI - Assessing persons with human immunodeficiency virus (HIV) infection using the Beck Depression Inventory: disease processes and other potential confounds. AB - Symptoms of Human Immunodeficiency Virus (HIV) infection and somatic symptoms of depression overlap, confounding clinical assessments of persons with HIV infection. This research examined the extent of this confounding. In Study 1, 71 persons with HIV infection demonstrated high rates of depression on the Beck Depression Inventory (BDI). However, depression scores correlated with symptoms of HIV infection. In Study 2, 63 persons with HIV infection also demonstrated high rates of depression on the BDI, and depression was again related to symptoms of HIV disease; specifically, persistent fatigue, diarrhea, night sweats, and muscle aches. Principal component factor analyses demonstrated that somatic symptoms of depression were closely associated with number of Acquired Immunodeficiency Syndrome diagnoses, number of HIV-related symptoms, and inversely related to number of T-helper cells. In contrast, cognitive-affective depression was most closely related to anxiety, hypochondriasis, and number of months since tested HIV positive. Results support the conclusion that depression scores require differential interpretations at different stages of HIV disease and that persons who have experienced HIV-related symptoms only be assessed for depression using instruments void of somatic symptoms. PMID- 7877095 TI - Implicit gender stereotyping in judgments of fame. AB - Implicit (unconscious) gender stereotyping in fame judgments was tested with an adaptation of a procedure developed by L. L. Jacoby, C. M. Kelley, J. Brown, and J. Jasechko (1989). In Experiments 1-4, participants pronounced 72 names of famous and nonfamous men and women, and 24 or 48 hr later made fame judgments in response to the 72 familiar and 72 unfamiliar famous and nonfamous names. These first experiments, in which signal detection analysis was used to assess implicit stereotypes, demonstrate that the gender bias (greater assignment of fame to male than female names) was located in the use of a lower criterion (beta) for judging fame of familiar male than female names. Experiments 3 and 4 also showed that explicit expressions of sexism or stereotypes were uncorrelated with the observed implicit gender bias in fame judgments. PMID- 7877096 TI - Longitudinal and behavioral analysis of masculinity and femininity in marriage. AB - Spouses' masculinity and femininity were examined in relation to longitudinal change in marital satisfaction and behavior displayed in a problem-solving discussion. Results indicated, first, that wives' satisfaction declined to the extent that their husband endorsed fewer desirable masculine traits (Study 1) and more undesirable masculine traits (Study 2). Second, masculinity and femininity covaried with problem-solving behavior, particularly for behavioral sequences involving husbands' responses to wives' negative behavior. Finally, the relation between husbands' masculinity and change in wives' satisfaction was not mediated by husbands' behavior; instead, sex role and behavioral variables made independent contributions to change in wives' satisfaction. These results are important because they highlight the value of examining intraindividual and interpersonal variables when determining how marriages improve and deteriorate. PMID- 7877097 TI - [Assessment of coronary stenosis severity using a Doppler guide wire in vivo: is the continuity equation applicable to moderate to severe coronary artery stenosis?]. AB - The usefulness of a Doppler guide wire was evaluated in the estimation of coronary stenosis severity in patients with moderate to severe coronary stenosis using the continuity equation. The maximal coronary flow velocities (V) proximal to the stenosis (p), at the stenosis (s), and distal to the stenosis (d) were measured using a Doppler guide wire (12-MHz, 0.018-in) in 12 patients with mild coronary stenosis (less than 50% diameter stenosis: group A) and 12 patients with moderate to severe coronary stenosis (more than 50% diameter stenosis: group B). Percent diameter stenosis (%DS) was calculated from Vp/Vs by: %DS = (1 - square root of Vp/Vs) x 100 (%) (Vp = the maximal velocity proximal to the stenosis; Vs = the peak velocity at the stenotic site) Percent DS was calculated from Vd/Vs by: %DS = (1 - square root of Vd/Vs) x 100 (%) (Vd = the peak velocity distal to the stenosis) Regression of Doppler-derived %DS from Vp/Vs compared to quantitative coronary angiographic % DS were: Group A: y = 0.83x + 3.0 (r = 0.79), Group B: y = 0.63x + 9.4 (r = 0.81), Overall: y = 0.63x + 9.6 (r = 0.91) Regression of Doppler-derived %DS from Vd/Vs compared to quantitative coronary angiographic %DS were: Group A: y = 0.98x - 1.0 (r = 0.81), Group B: y = 0.67x + 14.6 (r = 0.84), Overall: y = 0.79x + 7.6 (r = 0.91) The continuity equation method using a Doppler guide wire underestimates coronary stenosis severity in patients with moderate to severe coronary stenosis, although Doppler-derived %DS is correlated with angiographic %DS. PMID- 7877098 TI - [Preventive effect of pravastatin on restenosis following coronary angioplasty: prospective randomized trial]. AB - This study investigated the preventive effect of pravastatin on restenosis following successful transluminal coronary angiography (PTCA) in 109 consecutive patients. Patients were randomly and prospectively assigned to the pravastatin group (group P, n = 57) or the control group (group C, n = 52). The former received 10 mg/day pravastatin from the day of PTCA for 3 months. Restenosis was defined as a > or = 50% diameter stenosis at follow-up angiography with a > or = 15% reduction in luminal diameter compared to post-PTCA. The effect of pravastatin was analyzed in association with 7 clinical and 15 angiographic factors. Follow-up rate, serum lipid levels (total cholesterol, triglyceride, and HDL-cholesterol), and clinical and angiographic backgrounds except age and angularity of the lesions were not significantly different between the two groups at PTCA. Three months later, total cholesterol decreased from 222.3 +/- 35.1 to 179.2 +/- 31.2 mg/dl in group P, but was unchanged in group C (from 226.0 +/- 33.7 to 211.7 +/- 30.9 mg/dl). The restenosis rate was not different between the two groups (35.6 vs 35.7% per patient, 32.0 vs 33.3% per lesion). Moreover, no relationship between restenosis rate and serum total cholesterol level at follow up angiography was observed. Multivariate analysis, including 7 clinical and 15 angiographic factors, found neither pravastatin administration nor serum lipid levels were significantly correlated with decreased luminal diameter. Pravastatin (10 mg/day) did not reduce the incidence of restenosis after PTCA when administered from the day of PTCA for 3 months. PMID- 7877099 TI - [Pulsed Doppler findings of the pulmonary vein flow in mitral stenosis]. AB - Left atrial function was assessed by transesophageal echocardiography in 8 patients with mitral stenosis and sinus rhythm (MS group), and 16 age-matched normal controls (C group). Pulsed Doppler findings of left upper pulmonary vein flow were classified into first and second forward waves during systole (S1, S2), forward wave during diastole (D), and backward flow during left atrial contraction (PVA). Peak velocity (P) and time-velocity integral (TVI) of each wave and acceleration and deceleration slope of S2 wave (S2-Ac, S2-Dc) were obtained. TVI-S2 and P-D in the MS group were significantly lower than those in the C group (TVI-S2: 4 +/- 2 vs 12 +/- 3 cm, P-D: 27 +/- 13 vs 41 +/- 12 cm/sec). S2-Ac and S2-Dc in the MS group were significantly higher than those in the C group (S2-Ac: 456 +/- 116 vs 323 +/- 118 cm/sec2, S2-Dc: 380 +/- 102 vs 165 +/- 48- cm/sec2). There were no differences in S1 and PVA. Lower TVI-S2 in the MS group suggests decreased reservoir function of the left atrium. Lower TVI-S2 in the MS group was caused by increased S2-Ac and S2-Dc which suggests increased left atrial preload and deterioration of left atrial compliance. Decreased P-D in the MS group reflects dysfunction of mitral valve opening. PMID- 7877100 TI - [Usefulness of intracardiac echocardiography for guidance of transseptal puncture procedure]. AB - The clinical usefulness of intracardiac echocardiography (ICE) for the guidance of transseptal puncture procedure during percutaneous left heart bypass support (PLHBS) and percutaneous transvenous mitral commissurotomy (PTMC) was investigated to replace intraoperative transesophageal echocardiography monitoring which requires mild sedation and causes patient discomfort. The ICE procedure was assessed in 3 patients with PLHBS and 18 with PTMC using a 10 MHz rotating 8 French probe system especially developed for the purpose. Transseptal puncture procedure was observed by intraoperative ICE monitoring in the right atrium. The ICE images showed the transseptal puncture (Brokenbrough) needle as a point casting an acoustic shadow. By moving the ICE probe up and down, the excursion of the needle and its approach to the septal wall could be clearly observed. If the puncture needle is forced into the intra-atrial septum, the septal wall was clearly observed to protrude into the left atrium (tent formation). In a tent-formation the puncture site could be determined by ICE alone. Intracardiac echocardiography guidance was useful and may improve the safety and reliability of the transseptal puncture procedure in PLHBS and PTMC. PMID- 7877101 TI - [Feasibility of the left ventricular volume measurement by acoustic quantification method: comparison with ultrafast computed tomography]. AB - Acoustic quantification (AQ: the real-time automated boundary detection system) allows instantaneous measurement of cardiac chamber volumes. The feasibility of this method was evaluated by comparing the left ventricular (LV) volumes obtained with AQ to those derived from ultrafast computed tomography (UFCT), which enables accurate measurements of LV volumes even in the presence of LV asynergy, in 23 patients (8 with ischemic heart disease, 5 with cardiomyopathy, 3 with valvular heart disease). Both LV end-diastolic and end-systolic volumes obtained with the AQ method were in good agreement with those obtained with UFCT (y = 1.04 x - 16.9, r = 0.95; y = 0.87x + 15.7, r = 0.91; respectively). AQ was reliable even in the presence of LV asynergy. Interobserver variability for the AQ measurement was 10.2%. AQ provides a new, clinically useful method for real-time accurate estimation of the left ventricular volume. PMID- 7877102 TI - [Two cases of peripartum cardiomyopathy]. AB - Two cases of peripartum cardiomyopathy, a rare type of dilated cardiomyopathy, are reported. A 36-year-old woman developed congestive heart failure 1 month after delivering her third child. Cardiac catheterization revealed diffuse hypokinesis of the left ventricle and an ejection fraction of 28%. The second study, 20 months later, demonstrated an ejection fraction of 46%. Endomyocardial biopsy showed mild interstitial edema. A 42-year-old woman developed toxemia during pregnancy. She delivered her second child at 38 weeks of gestation. Two weeks later, she developed congestive heart failure. Cardiac catheterization demonstrated diffuse hypokinesis of left ventricle with an ejection fraction of 40%. Endomyocardial biopsy revealed dense fibrosis. Follow-up angiography performed 8 months later showed similar findings with an ejection fraction of 34%. These two cases suggest the importance of evaluation of endomyocardial biopsy to determine the degree of interstitial fibrosis that may reflect the prognosis for patients with peripartum cardiomyopathy confirmed by measurements of ejection fraction. PMID- 7877103 TI - [Is so-called "apex" really apex?]. PMID- 7877104 TI - [Adenosine triphosphate loading thallium-201 myocardial scintigraphy: optimal dose and diagnostic accuracy]. AB - Adenosine triphosphate (ATP) is an alternative to dipyridamole or adenosine in thallium-201 myocardial scintigraphy. However, the optimal dose of ATP has not been determined. A Doppler guide wire study showed the coronary flow velocity at a dose of 0.15 mg/kg of ATP was equal or higher than that at 0.14 mg/kg of adenosine or 0.56 mg/kg of dipyridamole. ATP was given intravenously to 67 patients with coronary artery disease at 0.15 mg/kg/min for 6 min. Thallium-201 was injected at 3 min, followed by immediate and delayed (3 hrs) tomographic imaging. There was no serious side effect during examination, although chest pain (26%), dyspnea (17%), and flushing (33%) were common. The sensitivity and specificity to detect coronary artery disease were 98 and 100%, respectively. The sensitivity to detect left anterior descending artery, left circumflex artery, and right coronary artery lesions was 94, 59 and 77%, respectively. ATP loading thallium-201 scintigraphy provides an accurate diagnosis of coronary artery disease. The optimal dose of ATP is 0.15 mg/kg/min for 6 min. PMID- 7877105 TI - Heel spur surgery. Another new approach. PMID- 7877106 TI - Candida albicans, the opportunist. A cellular and molecular perspective. AB - Candida albicans causes the majority of opportunistic fungal infections. The yeast's commensualistic relationship with humans enables it, when environmental conditions are favorable, to multiply and replace much of the normal flora. Virulence factors of C. albicans, enabling the organism to adhere to and penetrate host tissues, involve specific molecular interactions between the cells of the fungus and the host. Localized disease, such as oral candidiasis, onychomycosis, and vaginitis, results. These infections are usually limited to surfaces of the host, and can be quickly and successfully controlled by the use of one of the available antifungal agents. Candida albicans infections typically become systemic and life threatening when the host is immunocompromised. Depending on the immune defect in the host, one of the spectrum of Candida diseases can develop. If successful treatment of these patients is to be achieved, modulation of the immune deficit, as well as the use of an appropriate antifungal drug, must become a routine part of therapeutic interventions. PMID- 7877107 TI - Malignant eccrine acrospiroma. A case study. PMID- 7877108 TI - Stiffness of screw fixation and role of cortical hinge in the first metatarsal base osteotomy. AB - The authors investigated various factors that affect stiffness of screw fixation in the oblique first metatarsal osteotomy. One screw versus two screw fixation with intact medial cortical hinge, and two screw fixation without hinge were tested on the same metatarsal specimen. Mechanical properties of the fixation patterns were measured on a materials testing apparatus. Each metatarsal was tested at below failure threshold for stiffness within the elastic range of the specimen. Load versus displacement curves and fixation stiffness values were generated for axial loading, valgus torque, and plantar-to-dorsal cantilever bending. Osteotomies with an intact hinge demonstrated superior stiffness in most parameters as compared to osteotomies without a hinge. Two screw fixation with intact hinge showed significantly increased axial stiffness as compared to one screw fixation. There was no statistical difference between one and two screws in cantilever bending and torsional stiffness with an intact hinge. The major stabilizing factor of the first metatarsal base osteotomy is the medial cortical hinge. PMID- 7877109 TI - Tuberculosis of the foot. A diagnostic challenge. AB - Two cases of tuberculosis of the foot are described. The diagnosis for each was delayed and unexpected. The clinical features of osteoarticular tuberculosis are reviewed along with practical guidelines for diagnosis. PMID- 7877110 TI - Using ulcer surface area and volume to document wound size. AB - The evaluation of ulcer size is normally limited to measuring length, width, and depth, and comparing those figures to previously obtained values. These comparisons are grossly inaccurate, and a more representative technique can be used by treating the ulceration as a three-dimensional object. The author proposes several mathematical formulae that are easily computed on a hand-held calculator. The formulae use the measurements of length, width, and depth, and translate those dimensions into surface area and volume. PMID- 7877111 TI - Calcific leiomyoma. A unique case report. AB - Leiomyomas are benign soft tissue tumors originating in smooth muscle. They present clinically as a soft tissue mass causing a well localized, paroxysmal pain. Treatment of choice for such lesions is total excision. Recurrence or malignant transformation of these tumors is rare. Calcific leiomyomas, as diagnosed in this study, have seldom been reported in the foot. When treating lesions involving atopic calcification, it is important to maintain a high level of understanding of the various etiologies, both metabolic and nonmetabolic, which may lead to calcium deposition in the soft tissues. PMID- 7877112 TI - Fibrosarcoma of the heel. An unusual case report. PMID- 7877113 TI - Laboratory tests in depression: is it worth the effort? PMID- 7877114 TI - The combined dexamethasone/CRH test: a refined laboratory test for psychiatric disorders. AB - This report summarizes our extensive experience with the application of the DEX/CRH test to assess hypothalamic-pituitary-adrenal-system (HPA) alteration in patients with psychiatric disorders. The application of this combined dexamethasone suppression/CRH-challenge (DEX/CRH) test requires individuals to take 1.5 mg dexamethasone (DEX) at 23:00 h orally the previous night. On the day of the test, 100 micrograms human CRH are administered to the subjects under study at 15:00 h intravenously as a bolus, and blood samples for the determination of plasma cortisol and ACTH are drawn every 15 min from 14:00 h to 18:00 h. DEX/CRH-test results from 96 patients with major depression (MDE), 11 with a manic episode (MA), 9 with panic disorder (PD), 24 with a schizophrenic psychosis (SP), and 82 healthy control subjects served as the data base for this report. Three major conclusions can be drawn from statistical analysis of these data: 1. Psychiatric patients (n = 140), regardless of diagnostic classification, release significantly more cortisol and ACTH after DEX and additional CRH in comparison with age-matched controls. This hormonal release pattern (DEX CRH-test phenomenon) supports the assumption that psychiatric patients are prone to an altered glucocorticoid feedback regulation during the acute illness episode. This supports the notion that the DEX/CRH-test phenomenon constitutes a neuroendocrine sign of these various disorders and emphasizes the usefulness of the DEX/CRH test as a laboratory test to monitor the course of these disorders. 2. The sensitivity of the DEX/CRH test for MDE (about 80%) greatly exceeds that of the standard DST (1-2 mg of DEX), which has been reported to average about 44% in a meta-analysis of the literature data; in our sample the sensitivity of the DST was about 25%. 3. The sensitivity of the DEX/CRH test can be further increased to above 90% if subjects are clustered into four different age ranges: age < 35 years, age between 35 and 50 years, age between 50 and 70 years, and age above 70 years. 4. By reducing the time points of blood sampling for ACTH and cortisol to as few as five (15:00, 15:30, 15:45, 16:00, and 16:15 h), the DEX/CRH-test procedure becomes more convenient and more easily applicable without reducing its sensitivity. PMID- 7877115 TI - Adrenomedullary function in depressed patients. AB - In this paper from the Collaborative Depression Study (CDS)--Biological, a set of data analyses are presented which indicate that depressed states and perhaps depressed mood are associated with a greater activation of the adrenomedullary system than the sympathetic nervous system [as measured by norepinephrine (NE) and normetanephrine excretion]. For the most part this finding of predominant activation of the adrenomedullary system is seen in unipolar and not bipolar patients. PMID- 7877116 TI - Risk factors for anabolic-androgenic steroid use in men. AB - The illicit use of anabolic steroids to enhance athletic performance and physical appearance can cause numerous psychiatric and other adverse effects. In order to prevent steroid use and its negative consequences, knowledge of risk factors is needed. We conducted an anonymous survey of 404 male weight lifters from community gymnasiums who completed a 20-min, self-administered questionnaire. The sample for this study included all 35 men who were thinking about using steroids ("high-risk" nonusers), 50 randomly selected nonusers who were not thinking about using steroids ("low-risk" nonusers) and all 49 steroid users. The three groups differed in age, training characteristics, other performance-enhancers tried, body image, acquaintance with steroid users, and perception of negative consequences. When groups were compared along a continuum from low risk to high risk and from high risk to actual use, we found increasing amounts of competitive bodybuilding, performance-enhancers tried, and steroid-using acquaintances. Groups did not differ in their use of addictive substances. Nearly three-fourths of the high-risk group felt "not big enough," compared to 21% of the low-risk group and 38% of the steroid users (p < .001). These data suggest that steroids do work to increase satisfaction with body size, and that dissatisfaction with body size may contribute to the risk of using steroids. PMID- 7877117 TI - Sleep deprivation and bright light as potential augmenters of antidepressant drug treatment--neurobiological and psychometric assessment of course. AB - The present study was designed to investigate the clinical efficacy of trimipramine with adjunct sleep deprivation (SD) or bright light (BL) and to evaluate psychometric and neurobiological variables that might be of predictive value for treatment response. We used (1) the combined dexamethasone corticotropin releasing hormone test (DEX-CRH test) to characterize alterations of the hypothalamic-pituitary-adrenal (HPA) system; (2) polysomnography to evaluate sleep disturbances; and (3) a standardized test battery to assess cognitive psychomotor functions after study initiation and after 5 weeks of treatment. The overall response rate (> or = 50% decrease in score on Hamilton Rating Scale for Depression [HRS]) was 55% (N = 42). The response rate in the group with trimipramine monotherapy (N = 14) was 79%, whereas in the groups with adjunct SD (N = 14) and BL (N = 14), respectively, it was only 43%. All three groups showed significant improvement at the end of the third week of treatment. Neither of the adjunct treatments hastened the onset of antidepressant action as measured by HRS. A significantly higher proportion of nonresponders than responders (p < .05) had HPA dysregulation, disturbed rapid eye movement (REM) sleep (REM latency, REM% first third of night) and decreased non-REM sleep (% stage 2). The non-responders showed significantly more corticotropin (ACTH) secretion after CRH stimulation in the DEX-CRH test than the responders and a less rapid normalization of the neuroendocrine dysregulation (cortisol secretion) (p < .01). In addition, REM latency was significantly shorter in the BL group than in the monotherapy group and estimated duration of illness significantly longer in the SD group than in the monotherapy group. REM latency, percentage of REM sleep during the first third of the total sleep period, percentage of non-REM sleep stage 2 and ACTH release after a DEX-CRH challenge predicted response across all three treatment groups. The neurobiological symptoms were unevenly distributed, among the three groups, thus creating heterogeneity in these measures. This heterogeneity may have contributed to the different treatment response rates as defined by psychopathology (HRS). In contrast, the neuropsychological tests and some of the sleep-EEG investigations revealed different response patterns for different groups: The onset of improvement in simple cognitive functions and in sleep continuity was earlier in the adjunct treatment groups. This study underlines the need for a multidimensional approach including use of neurobiological and neuropsychological measures to identify the therapeutic profiles of different treatment strategies and predictors of outcome. PMID- 7877118 TI - Experimental evidence for two dimensions of cognitive disorders in depressives. AB - Three neuropsychological tests (Rey's auditory verbal learning test, word fluency and signal detection test for words) were administered to 36 depressed patients (medicated and non-medicated) and 26 controls and compared to scale scores for depression severity and psychomotor retardation to examine how retardation was related to cognitive performance. As expected, compared to controls depressives exhibited non-specific "cognitive inefficiency", that is, consistently deficient performance in all cognitive tasks. Results on all three tests were correlated with one other and with depressive severity (measured by the Montgomery & Asberg Depression Rating Scale, MADRS). One notable exception, however, was the score for commission errors ("false alarms") in the signal detection test, which correlated negatively with psychomotor retardation (measured by a subscale of the Salpetriere Retardation Rating Scale, SRRS) but not at all with depressive severity. Lack of commission errors thus seemed to index a dimension of retardation of ideation that seemed distinct from the non-specific cognitive inefficiency dimension. Conversely, omission errors in the same test strongly correlated with the other two cognitive tests and with depressive severity but not with psychomotor retardation. Cognitive performance in depressives might thus be explainable in terms of two overlapping dimensions of depressive pathology (global cognitive impairment vs. specific effect of retardation). Further studies with non-medicated patients are needed to determine to what extent these findings may be due to medication effects. PMID- 7877119 TI - The psychiatric assessment of liver transplant patients with alcoholic liver disease: a review. AB - Patients with severe alcoholic liver disease are receiving liver transplants in increasing numbers. Alcoholic liver transplant patients appear to have a good prognosis, yet alcoholic candidates may be rejected on psychiatric grounds alone. The role of the psychiatrist in the multidisciplinary assessment is discussed and the use of a number of predictors of outcome for alcoholic candidates considered. Studies examining these variables have many methodological limitations and it is therefore very difficult to draw any firm conclusions on their validity or reliability. Long-term prospective studies using appropriate measures of outcome should enable the liaison psychiatrist to provide more useful advice on the psychosocial outcome and treatment requirements of this growing group of patients. PMID- 7877120 TI - Sexual functioning post-myocardial infarction: effects of beta-blockers, psychological status and safety information. AB - Impaired sexual functioning limits the quality of life of 34-75% of post myocardial infarction (MI) patients. This study examined the effects of three factors: (a) beta-blocker intake, (b) psychological distress, and (c) information about safety of sexual activity, on post-MI decreased sexual functioning. Sixty three male post-MI, post-cardiac rehabilitation patients and their spouses participated in the study. Analyses of partial variance were conducted to test for the effect of each factor on sexual functioning. Controlling for age, results revealed that patients' psychological distress explained uniquely 24% of the variance on decreased post-MI sexual activity (p < 0.002). Beta-blocker intake and message received with regard to sexual activity safety were not significant predictors of observed changes. Interdisciplinary assessments and interventions are recommended. PMID- 7877121 TI - Comparative predictive value of attributional style, negative affect, and positive affect in predicting self-reported physical health and psychological health. AB - The main aim of the study was to determine the comparative predictive value of affect and attributions in predicting emotional and physical health. Secondary aims were to determine the comparative value of attributional, affect variables, in predicting health. Two hundred and forty subjects completed scales for the assessment of attributions, and negative and positive affect. Subjects also answered self-report questions on emotional health, physical health, number of visits to doctors for medical advice, illness, and days absent from work. The analysis of relative importance of attributional and affect variables in predicting health revealed that negative affect caused by thoughts was the best predictor of psychological health and physical health; there was some indication that positive affect caused by thoughts was the next best predictor of health. Analysis of the predictive value of attributional variables only, revealed that: (a) attributional style for bad events was a better predictor of health than attributional style for good events; and (b) of all the attributions made for good events and bad events, global attributions for bad events were the best predictor of health. Analysis of the predictive value of affect variables only showed that: (a) negative affect was a better predictor of health than positive affect; and (b) of negative affect and positive affect caused by thoughts and day to-day experiences, negative affect caused by thoughts was the best predictor of health. PMID- 7877122 TI - Alexithymia--state or trait? One-year follow-up study of general hospital psychiatric consultation out-patients. AB - We carried out a 1-year follow-up study on 54 out of 80 general hospital psychiatric consultation out-patients. Alexithymic features were measured by the Toronto Alexithymia Scale (TAS), and self-reported psychological distress with the Brief Symptom Inventory (BSI). Men were more alexithymic and distressed than women both at the baseline and at the follow-up evaluations. The degree of alexithymia in both genders remained consistent, whereas psychological distress decreased significantly in both genders during the follow-up period. Therefore we conclude that alexithymia presents a constant trait in psychiatric consultation out-patients. PMID- 7877123 TI - The integration of alternative treatment modalities in HIV infection--the patient's perspective. AB - The relationship between professionals representing conventional treatment (CT) and professionals representing non-conventional therapies (alternative therapy (AT) and/or psychotherapy (PT)) is usually characterized by mutual scepticism and mistrust, the overriding fear being that either side will evoke unjustified hopes or will provide false treatment. We investigated whether patients with HIV infection had unrealistic hopes in non-conventional treatment (non-CT), to what extent they use non-CT, and whether perceived benefit and harm differ between the two modes of treatment. We examined a sample of 100 patients with documented HIV infection in the out-patient department using a self-developed questionnaire, the Hospital Anxiety and Depression Scale (HAD) and data concerning the HIV status. Fifty-six patients used AT and/or PT. Severity of HIV disease did not differ between users and non-users of non-CT. The most important reasons for the use of AT were 'strengthening the body and resistance; supplementing conventional therapy'. Users of non-CT rated the competence of CT lower than non-users in solving medical problems (VAS-scores 0-100: 65.5 +/- 17.6 vs 76.3 +/- 17.7; p = 0.003) and in solving emotional problems (VAS scores 0-100: 35.8 +/- 21.2 vs 48.2 +/- 28.9; p = 0.02). Users of non-CT were significantly more anxious 8.4 +/- 4.8 vs 5.5 +/- 4.6; p = 0.004) and more depressive (5.7 +/- 4.5 vs 3.7 +/- 4.5; p = 0.03) than non-users. Expectations and hopes did not differ between users of AT and non-users: main hopes were a delay of disease progression (76% vs 71%) and an alleviation of symptoms (78% vs 66%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877124 TI - The applicability of antidepressants in the depressed medically ill: an open clinical trial with fluoxetine. AB - In the literature the side-effects and medical complications of tricyclic antidepressants (TCAs), in the medically ill have been extensively reviewed. This study uses a prospective design to examine these issues' questions in an almost solely in-patient C-L population (N = 37) treated with a serotinergic antidepressant (fluoxetine). A first remarkable finding is the fact that 83% of the patients have complaints comparable with the side-effects of the drug, prior to its administration. Second, although the drop-out rates (DO) are comparable with those in earlier studies, in this study DO do not seem to be related to the seriousness of the side-effects of the drug. The more serious side-effects were hyponatremia (N = 1) and gastrointestinal symptoms (N = 3). In contrast to TCAs no psychiatric side-effects have to be reported. Therefore this study suggests that with good medical supervision fluoxetine can be used in the treatment of seriously medically ill patients with depressive co-morbidity. PMID- 7877125 TI - The role of psychological coronary risk factors in insulin and glucose metabolism. AB - The association between psychological coronary risk factors and serum insulin, and C-peptide and blood glucose concentrations, [the latter measured while fasting and during the oral glucose tolerance test (OGTT)], was examined in healthy middle-aged men (n = 64). The results indicate that among the evaluated psychological risk factors, high levels of hostile paranoia and vital exhaustion were most consistently associated with an enhanced insulin/glucose ratio, and enhanced insulin, C-peptide and glucose responses during OGTT. The associations persisted after controlling for age, smoking, alcohol consumption and visceral fat distribution. Thus, in addition to age, life-style factors and obesity, psychological factors may have an effect on insulin and glucose metabolism. PMID- 7877126 TI - Physical symptoms in post-traumatic stress disorder. AB - Physical complaints are recognised accompaniments of Post-Traumatic Stress Disorder (PTSD). This study investigates the reporting of physical complaints in a treatment-naive sample of fire-fighters with and without PTSD. Statistically higher rates of cardiovascular, respiratory, musculoskeletal and neurological symptoms were reported in the PTSD group. Possible explanations are discussed, with an exploration of the contribution of arousal, disordered information processing, dissociation, comorbid diagnoses and premorbid personality. The role of the original stressor and sociocultural issues are explored. PMID- 7877127 TI - Hostility and myocardial infarction in men. AB - This case-control study examines the association of hostility (as measured by the Cook-Medley Hostility Scale) with myocardial infarction in adult males from The Netherlands. Subjects included patients with first myocardial infarction (MI; N = 81), who were compared with a neighbourhood control (NC) group (N = 168). Cases had somewhat higher scores on the Cook-Medley Hostility Scale, although the differences between cases and controls were not statistically significant. Multivariate analysis revealed the presence of an interaction between hostility and age, suggesting that the association of hostility with MI is age-dependent. The results indicate that hostility only constitutes a risk indicator for first MI in men who are younger than 50 yr of age. PMID- 7877128 TI - Psychotherapy in functional dyspepsia. AB - Patients with functional dyspepsia were assigned at random to cognitive psychotherapy (10 sessions of 50 min duration, n = 50) or to a control group (no treatment, n = 50). Before treatment all patients were assessed on psychological, somatic and lifestyle factors. If allocated to the therapy group all patients were also asked to define the main problems they wanted to discuss in therapy ('target complaints'). The patients were evaluated at the end of therapy (after 4 months) and at 1 yr follow-up. Outcome measures were dyspeptic symptoms, scores on 'target complaints' and psychological parameters. Both groups showed improvement in dyspeptic and psychological parameters after 1 yr. The improvement in the control group was attributed to a non- specific effect of increased interest and attention. The therapy group showed greater reduction than the control group on dyspeptic symptoms [days of epigastric pain (p = 0.050), nausea (p = 0.024), heartburn (p = 0.021), diarrhoea (p = 0.002) and constipation (p = 0.047)]; and on scores on 'target complaints' (p = 0.001). PMID- 7877129 TI - Psychosocial functioning of young adults after surgical correction for congenital heart disease in childhood: a follow-up study. AB - To investigate the long-term psychosocial outcome of congenital heart disease, the emotional, intellectual and social functioning of 288 (young) adult patients was assessed with standardized assessment procedures 9-23 years (mean follow-up interval: 16 years) after surgical correction for congenital heart disease in childhood, and compared with that of reference groups. With respect to emotional functioning, the patients reported significantly fewer feelings of hostility, fewer neurotic complaints and a better self-esteem than reference subjects. Overall, the results concerning social functioning showed favourable outcomes on daily activities (school, employment) and leisure-time activities for (young) adults with congenital heart disease. No significant differences were found between scores of different cardiac diagnostic groups on hostility, neuroticism, self-esteem and leisure-time activities. The possibility whether the 'denial' mechanism might have contributed to the positive outcomes is discussed. PMID- 7877130 TI - Post-vasectomy erectile dysfunction. AB - We investigated two groups of men with regard to vasectomy acceptance, and subsequent erectile dysfunction. Group I was a group of 45 men chosen at random from 254 vasectomized patients. Group II was a group of 18 men who, out of 180 patients treated for erectile dysfunction, attributed their dysfunction to previous vasectomy. We analysed the social background, motivation for vasectomy and postoperative changes of sexual life or behaviour of the partners. The partnership constellation, particularly the role of a predominant female partner seems to be an important feature for vasectomy acceptance. Low acceptance might cause erectile dysfunction. PMID- 7877131 TI - Menstrual-cycle effects on mood and perceptual-motor performance. AB - Fifty-four participants took part in a study to evaluate the effects of the menstrual cycle on mood and the performance of a perceptual-motor task. The task involved tracking a randomly-moving circle on a computer screen with a joystick controlled dot. Women were tested on three occasions, during the premenstrual, menstrual and ovulatory phases. Each testing session involved completing the Menstrual Distress Questionnaire, the monopolar Profile of Mood States questionnaire and performing five, timed trials on the task. A control group of male participants completed the Profile of Mood States questionnaire on three separate occasions over 28 days according to a pseudo-menstrual cycle experimental protocol. Results revealed that females experienced low energy and impaired cognitive function, both premenstrually and during menstruation. Task performance did not vary with menstrual-cycle phase, suggesting that they either tried to compensate for a lack of well being, or that negative mood was of insufficient magnitude to manifest a performance change. The findings suggest that when the purpose of an assessment is disguised, typically-reported menstrual cycle and mood-related effects on performance are not observed reliably. PMID- 7877132 TI - Depression in anorexia nervosa and bulimia nervosa: discriminating depressive symptoms and episodes. AB - In a clinical sample of 198 female patients with anorexia nervosa (N = 83) and bulimia nervosa (N = 115), 43% met criteria for major depression using the Structured Clinical Interview for DSMIII-R. This group had a mean score of 30.9 +/- 8.7 on the Beck Depression Inventory (BDI) which was significantly higher than the BDI mean score of 20.5 +/- 8.9 among the remainder of the sample (p < 0.0001). A score of 26 yielded the highest levels of sensitivity and specificity, while five items from the BDI (loss of satisfaction, discouragement, weight loss, suicidal ideation and decision-making) correctly classified approximately 80% of subjects into "depression-positive" or "depression-negative" categories. Detection of co-morbid depression in patients with eating disorders may have practical implications for treatment. PMID- 7877133 TI - Expression of alpha-bungarotoxin receptor subtypes in chick central nervous system during development. AB - Chick central nervous system (CNS) expresses alpha-bungarotoxin (alpha Bgtx) receptors. We have recently reported the purification and characterization of two alpha Bgtx receptor subtypes, alpha 7 and alpha 7-alpha 8 from chick optic lobe (COL). In order to study whether other alpha Bgtx receptor subtypes are present in other areas of the chick CNS, as well as their developmental expression, we used anti-alpha 7 and anti-alpha 8 subunit-specific antibodies to study alpha Bgtx receptors at different developmental stages in COL, brain and retina. We found that only the alpha 7 and alpha 7-alpha 8 subtypes are present at all developmental stages in chick COL and brain, where they represent 90% of all the alpha Bgtx receptors at embryonic day 19 and 1 day post hatching (D1). In chick retina, an alpha 8 subtype representing 50% of all alpha Bgtx receptors at D1 is present in addition to the alpha 7 and alpha 7-alpha 8 subtypes, and the expression of this alpha 8 subtype increases during neurodevelopment. PMID- 7877134 TI - In situ characterization of renal insulin receptors in the rat. AB - Insulin regulates carbohydrate metabolism, and water, sodium, potassium, and phosphate reabsorption in the kidney by binding to specific receptors. Insulin receptors have been identified in the kidney using membrane preparations obtained from both glomeruli and tubules. In this study, an autoradiographic technique was used to characterize insulin receptors in the rat kidney. Frozen tissue sections were preincubated to remove endogenously bound insulin, incubated in a buffer containing 200 microM 125I-Tyr-insulin, washed, and dried before exposure on Ultrofilm. Binding density was assessed by computerized microdensitometry. In the cortex, binding density was comparable in glomeruli and tubules. In the medulla, bound radioligand was found primarily in longitudinal structures traversing the outer portion, presumably corresponding to vascular bundles, and in the inner portion. Scatchard analysis of competition binding data resulted in curvilinear profiles, indicating either two classes of receptors with different affinity or the presence of a single class of receptors with a negative cooperative hormone receptor interaction. Data analyzed for a two-site model showed one receptor site with Kd of 0.39 +/- 0.14 nmol/l and Bmax of 3.5 +/- 1.0 x 10(10) receptors/mm3 and another site with Kd of 0.30 +/- 1.1 pmol/l and a Bmax of 3.2 x 10(13) receptors/mm3. Thus, in situ autoradiography can be used to determine distribution and binding characteristics of insulin receptors in rat kidney and might be employed in receptor studies on rat models of human disease. PMID- 7877135 TI - Characterization of mammalian Gs-alpha proteins expressed in yeast. AB - The guanine nucleotide regulatory protein, GS, mediates transmembrane signaling by coupling membrane receptors to the stimulation of adenylyl cyclase activity. The full length coding sequences for the M(r) = 42-45,000, short form (S), and M(r) = 46-52,000, long form (L), of the alpha-subunits of rat GS were placed in yeast expression vectors under the regulatory control of the copper-inducible CUP1 promoter and transformed into Saccharomyces cerevisiae. In the presence of 100 microM CuSO4, the transformed yeast expressed GS-alpha mRNAs and proteins. In reconstitution experiments, rat GS-alpha(S and L), solubilized from yeast membranes with 1% cholate, conferred NaF-, (-)isoproterenol-, and guanine nucleotide-dependent sensitivity to adenylyl cyclase catalytic units in S49 lymphoma cyc- cell membranes, which are devoid of endogenous GS-alpha. GS-alpha (S) demonstrated twice the activity of GS-alpha(L) in reconstitution assays of fluoride-stimulated adenylyl cyclase activity. Comparison of GS-alpha (S) expressed in yeast with GS purified from rabbit liver or human erythrocytes showed that the crude recombinant protein was fully competent in reconstituting NaF-stimulated adenylyl cyclase activity, but was only 2-5% as potent as purified GS. Addition of bovine brain beta gamma subunits during reconstitution enhanced all parameters of adenylyl cyclase activity for GS-alpha(S and L) obtained from yeast. In contrast, transducin beta gamma only enhanced agonist-stimulated adenylyl cyclase activity for GS-alpha (S and L) following reconstitution. These results demonstrate that the expression of functional mammalian GS-alpha subunits in yeast may be useful for their biochemical characterization. PMID- 7877136 TI - Antibody binding to the juxtamembrane region of the insulin receptor alters receptor affinity. AB - The effect of three antibodies that interact with distinct regions of the insulin receptor (the alpha subunit (83-7), the juxtamembrane region near tyrosine 960 (960) or the carboxy terminal region of the beta subunit (CT-1) on insulin binding was examined. Detergent-solubilized insulin receptors from IM-9 cells immobilized on Sepharose beads by 960 antisera bound 2-3 times more 125I-insulin tracer (25-60 pM) than receptors immobilized with either 83-7 or CT-1. Pre incubation of solubilized receptors with either 83-7 or 960 resulted in equivalent depletion (90%) of insulin binding activity from solubilized IM-9 cell extracts, suggesting that both antibodies were in excess and capable of binding a similar population of receptors. Antibody 960, but not CT-1 or 83-7, also increased insulin binding 2 fold to solubilized receptors precipitated with polyethylene glycol. To determine whether the altered binding observed with antibody 960 was due to increased affinity of the receptor for insulin or appearance of more insulin binding sites, binding studies were performed over a wide range of insulin concentrations. Analysis of the resulting binding curves indicated that 960 increased the affinity of the receptor for insulin 3 fold over control (kd = 0.3 nM for 960, and 0.9 nM for 83-7, respectively). The antibody 960 also specifically increased insulin binding to intact, saponin-permeabilized IM-9 cell membranes. These results indicate that binding of 960 antibody to the juxtamembrane region of the insulin receptor alters the affinity of the receptor for insulin. Since tyrosine 960 in the juxtamembrane region has been suggested to play a role in receptor signalling, changes in receptor conformation in this region that are likely to account for the change in affinity may play a role in signal transduction. PMID- 7877137 TI - Isolation and characterization of neurokinin A receptor cDNAs from guinea-pig lung and rabbit pulmonary artery. AB - cDNA clones for NK-2 receptors (NK-2R) were isolated from guinea-pig lung (GPl) and rabbit pulmonary artery (Rpa) using a polymerase chain reaction based methodology. The GPl NK-2R consists of 402 amino acids and encodes a protein with a relative molecular mass of 45,097. The Rpa NK-2R consists of 384 amino acids and encodes a protein with a relative molecular mass of 43,169. The GPl and Rpa NK-2Rs share significant amino acid sequence homology amongst themselves (90.1%), as well as with human, bovine, hamster and rat NK-2 receptors. The two receptors were stably transfected into mouse erythroleukemia cells, high-speed membranes were prepared from induced cells and their pharmacological properties examined utilizing [3H]-NKA in a receptor-binding assay. [3H]NKA bound to both NK-2Rs with high affinity (KD = 2-7 nM) and saturable (Bmax = 633-9000 fmol/mg protein) manner which was inhibited by GTP analogs. Competition experiments with agonists demonstrated identical order of potency in both NK-2Rs; NKA > [Nle10]NKA(4-10) > [beta-Ala8]NKA(4-10) > > Substance P > > > Senktide. Similarly, an identical profile for both receptors was observed with selective NK-2 antagonists: SR48,968 > MEN10,376 > > R396. The rank order of antagonist affinity is consistent with that in cloned human NK-2R and the observations of NK-2 receptor pharmacology in native human, guinea pig and rabbit tissues. PMID- 7877138 TI - Sarafotoxin-induced calcium mobilization in cultured dog tracheal smooth muscle cells. AB - Sarafotoxin b (S6b)-induced changes in intracellular Ca2+ concentration ([Ca2+]i) were monitored in cultured canine tracheal smooth muscle cells (TSMCs) by a fluorescent Ca2+ indicator fura-2. S6b elicited an initial transient peak followed by a sustained elevation of [Ca2+]i. BQ-123, an endothelin-A (ETA) receptor antagonist, had a high affinity to block the rise in [Ca2+]i response to S6b. In the absence of external Ca2+, only an initial transient peak of [Ca2+]i was seen, the sustained elevation of [Ca2+]i could then be evoked by addition of 1.8 mM Ca2+. Ca2+ influx was required for the changes of [Ca2+]i, since the Ca(2+)-channel blockers, diltiazem, verapamil, and Ni2+, decreased both the initial and sustained elevation of [Ca2+]i in response to S6b. TSMCs pretreated with phorbol 12-myristate 13-acetate (PMA, 1 microM) for 30 min attenuated Ca2+ mobilization induced by S6b, which was reversed by staurosporine, a protein kinase C (PKC) inhibitor. The change of [Ca2+]i induced by S6b was attenuated by cholera toxin pretreatment, but not by pertussis toxin. These data demonstrate that the initial detectable increase in [Ca2+]i stimulated by S6b is due to the activation of ETA receptors and subsequent release of Ca2+ from internal stores, whereas the contribution of external Ca2+ follows and partially involves a diltiazem- and verapamil-sensitive process. The inhibition of PMA on S6b-induced Ca2+ mobilization was inversely correlated with membraneous PKC activity. PMID- 7877139 TI - Orally bioavailable benzisothiazolone inhibitors of human leukocyte elastase. AB - Human leukocyte elastase (HLE) has been proposed as a primary mediator of pulmonary emphysema and other inflammatory airway diseases. HLE is capable of cleaving many proteins, including elastin, other components of connective tissue, certain complement proteins, and receptors. Under normal conditions an appropriate balance exists in the lung between HLE and endogenous inhibitors, which scavenge the released enzyme before it exerts deleterious effects in the lung. Emphysema is thought to result from an imbalance in the lung between HLE and endogenous inhibitor (elevated elastase or insufficient inhibitor) that leads to the destruction of alveoli. We have identified WIN 64733 (2) and WIN 63759 (3) as potent (Ki* = 14 and 13 pM, respectively), selective, mechanism-based inhibitors of HLE which are orally bioavailable in the dog (absolute bioavailability 46% and 21%, respectively). In this series the in vitro stabilities of the inhibitors in blood, jejunal homogenates, and liver S9 homogenates are useful predictors of oral bioavailability. After being administered orally (30 mg/kg) to dogs, compounds 2 and 3 are found in the lung, being detected in the epithelial lining fluid obtained by bronchoalveolar lavage (Cmax of 2.5 and 0.47 microgram/mL, respectively). PMID- 7877140 TI - 2,4-Diamino-5-substituted-quinazolines as inhibitors of a human dihydrofolate reductase with a site-directed mutation at position 22 and of the dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii. AB - 2,4-Diaminoquinazoline antifolates with a lipophilic side chain at the 5 position, and in one case with a classical (p-aminobenzoyl)-L-glutamate side chain, were synthesized as potentially selective inhibitors of a site-directed mutant of human dihydrofolate reductase (DHFR) containing phenylalanine instead of leucine at position 22. This mutant enzyme is approximately 100-fold more resistant than native enzyme to the classical antifolate methotrexate (MTX), yet shows minimal cross resistance to the nonclassical antifolates piritrexim (PTX) and trimetrexate (TMQ). Although they were much less potent than trimetrexate and piritrexim, the lipophilic 5-substituted analogues were all found to bind approximately 10 times better to the mutant DHFR than to the wild-type enzyme. The potency of the analogue with a classical (p-aminobenzoyl)-L-glutamate side chain was similarly diminished in comparison with MTX, but the difference in its binding affinity to the two DHFR species was only 5-fold. Thus, by making subtle structural changes in the antifolate molecule, it may be possible to attack resistance due to mutational alterations in the active site of the target enzyme. Also, to test the hypothesis that DHFR from Pneumocystis carinii and Toxoplasma gondii may have a less sterically restrictive active site than the enzyme from mammalian cells, inhibition assays using several of the lipophilic analogues in the series were carried out against the P. carinii and T. gondii reductases in comparison with the enzyme from rat liver. In contrast to their preferential binding to mutant versus wild-type human DHFR, binding of these analogues to the P. carinii and T. gondii enzymes was weaker than binding to rat enzyme. It thus appears that, if the active site of the DHFR from these parasites is less sterically restrictive than the active site of the mammalian enzyme, this difference cannot be successfully exploited by moving the side chain from the 6 position to the 5-position. PMID- 7877141 TI - Structure-activity studies of 2,3,4,4a,5,9b-hexahydroindeno[1,2-c]pyridines as antispermatogenic agents for male contraception. AB - Analogs of (4aRS,5SR,9bRS)-2-ethyl-2,3,4,4a,5,9b-hexahydro-7-meth yl-5-p- tolyl 1H-indeno[1,2-c]pyridine (Sandoz 20-438, 10a; R1 = ethyl, R2 = R3 = methyl, R4 = H) have been synthesized and tested in mice for their ability to reduce testes weight and disrupt spermatogenesis. The activity was strongly dependent on stereoisomerism and chirality, consistent with a mechanism of action involving interaction with a specific macromolecule. It was affected by changes in the nitrogen substituent and most strikingly by changes in the p-substituent of the 5 aryl ring. A hydrogen, fluorine, hydroxy, or methoxy substituent led to loss of activity, whereas methyl (Sandoz 20-438, 10a), carboxylate (RTI-4587-054, 10k; R1 = ethyl, R2 = methyl, R3 = COOH, R4 = H), ester (RTI-4587-056, 12b; R1 = ethyl, R2 = methyl, R3 = COOMe, R4 = H), formyl (RTI-4587-030, 12i; R1 = ethyl, R2 = methyl, R3 = CHO, R4 = H), or hydroxymethyl (RTI-4587-055, 12g; R1 = ethyl, R2 = methyl, R3 = CH2OH, R4 = H) groups resulted in antispermatogenic compounds. Methyl ester 12b was an effective antifertility agent, without apparent effects on mating, when given orally to male mice at 7-15 mg/kg daily for 35 days. Further evaluation of these compounds as male contraceptive agents and probes for study of spermatogenesis appears warranted. PMID- 7877142 TI - Antimalarial activity of new dihydroartemisinin derivatives. 6. alpha Alkylbenzylic ethers. AB - A series of diastereomeric dihydroartemisinin alpha-alkylbenzylic ethers was synthesized in search for analogs with higher antimalarial efficacy and longer plasma half-life than the existing artemisinin derivatives. Artelinic acid was used as the model molecule for the design of new analogs. Two approaches were taken in an attempt to (a) increase the lipophilicity of the molecule and (b) decrease the rate of oxidative dealkylation of the target compounds. All compounds in this study showed at least equal or better in vitro antimalarial activity against Plasmodium falciparum than artelinic acid. The most active compounds of this series showed 10-, 20-, and 40-fold better inhibitory activity than artemether, artemisinin, and artelinic acid, respectively. Compounds which have a small methyl group substituted at the alpha-methylene group showed weaker activity than compounds with a larger carbethoxyalkyl substituent, indicating that the lipophilicity and the steric effect of the molecules play important roles in their antimalarial activity. This fact is further substantiated by the significantly weaker antimalarial activity of the carboxylic acids than their corresponding esters. Compounds with electron-withdrawing function (NO2) substantially increase the antimalarial activity. The S-diastereomers, in general, are severalfold more potent than the corresponding R-isomer. PMID- 7877143 TI - Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo [4,5,1 jk][1,4]benzodiazepin-2(1H)-one (TIBO) derivatives. 3. AB - 4,5,6,7-Tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2 (1H)-ones (TIBO), 1, have been shown to significantly inhibit HIV-1 replication in vitro by interfering with the virus's reverse transcriptase enzyme. They have also demonstrated potential clinical efficacy in combating HIV-1, on the basis of a preliminary study. Our prior publications have discussed the discovery of this series of compounds and reported some preliminary chemical and biological studies around N-6 substitutions and 5-membered ring variations of 1. This manuscript describes our synthetic endeavors around 4, 5, and 7 mono- and disubstitutions of 1 and discusses related HIV-1 inhibitory structure-activity relationships. On the basis of inhibition of HIV-1's cytopathic effects in MT-4 cells, we found that 5 mono-Me-substituted analogues, the original substitution in the early lead compounds, and 7-mono-Me-substituted analogues of 1 were comparable as being consistently the most active compounds. Although generally less active, the 4,5,7 unsubstituted, 4-mono-substituted, cis- and trans-5,7-di-Me-substituted, and cis 4,5-di-Me-substituted analogues of 1 also exhibited some significant desired activity. The remaining trans-4,5-di-Me-substituted, cis- and trans-4,7-di-Me substituted, and all 4,5-, 5,6-, 6,7-, and 7,8-fused disubstituted analogues of 1 possessed no noticeable desired activity. PMID- 7877144 TI - Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo-[4,5,1 jk][1,4]benzodiazepin- 2(1H)-one (TlBO) derivatives. 4. AB - In previous papers, we have described the discovery of a new series of compounds, 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1 H)- ones, TlBO (1 and 1a), with potent anti-HIV-1 activity and the synthesis of analogues to better define the structure-activity relationships (SAR) in terms of changes in substituents at the N-6 position and variations of the five-membered urea ring as well as the seven-membered diazepine ring. This paper describes the synthesis of TlBO analogues with various substitutents on the aromatic ring and their SAR in terms of anti-HIV-1 properties. Substituents on the 8-position furnished the most rewarding results and gave a large improvement in potency versus the parent compound. These included halogen, thiomethyl, and methyl. Analogues like 8-cyano, -methoxy, and -acetylene were equipotent, while 8-amino, -acetylamino, dimethylamino, and -nitro were inactive (Table 1). Substituents at the 9-position tended to have little effect on activity, and 10-substituents decreased activity. The 8-chloro compound 6a with IC50 = 0.0043 microM is currently under clinical development. PMID- 7877145 TI - [[[(Thienylcarbonyl)alkyl]oxy]phenyl]- and [[[(pyrrylcarbonyl)alkyl]oxy]phenyl]oxazoline derivatives with potent and selective antihuman rhinovirus activity. AB - As an approach to more extensive structural modifications of [(oxazolylphenoxy)alkyl]isoxazoles, we synthesized new compounds characterized by the replacement of the isoxazole nucleus with furan, pyrrole, and thiophene rings and by the presence of a ketocarbonyl group in the aliphatic chain connecting these pentatomic heterocycles to the 4-(4,5-dihydro-2-oxazolyl)phenoxy, 4 (ethoxycarbonyl)phenoxy, and 4-carboxyphenoxy moieties. Some pentamethylene derivatives were also prepared, and their antirhinovirus activity was compared to that of the corresponding ketomethylene derivatives. Syntheses were carried out by Friedel-Crafts acylation of the above pentatomic heterocycles and subsequent reaction of chloroalkyl ketones with the proper 4-substituted phenol. Reduction of the ketone function afforded the related polymethylene derivatives. The new compounds were tested for antirhinovirus activity and cytotoxicity in comparison with WIN 51711, used as reference drug. Inspection of the structure-activity relationships revealed that the thiophene ring and the carbonyl group are the structural components which to a large extent contribute to the positive biological profile in terms of both wideness of spectrum and low cytotoxicity. Among the various derivatives, compounds 8e,d showed in vitro the same potency of WIN 51711 but a cytotoxicity at least 10 times lower. PMID- 7877147 TI - Synthesis of 11 beta-[18F]fluoro-5 alpha-dihydrotestosterone and 11 beta [18F]fluoro-19-nor-5 alpha-dihydrotestosterone: preparation via halofluorination reduction, receptor binding, and tissue distribution. AB - We have prepared 11 beta-fluoro-5 alpha-dihydrotestosterone (11 beta-F-DHT, 1) and 11 beta-fluoro-19-nor-5 alpha-dihydrotestosterone (11 beta-F-19-nor-DHT, 2) in order to investigate the properties of these new androgens labeled with fluorine-18 as potential androgen receptor (AR)-based imaging agents for prostate cancer. These compounds were synthesized in 6 steps from hydrocortisone and in 13 steps from 1,4-androstadiene-3,11,17-trione, respectively. Relative binding affinities (RBA) of 11 beta-F-DHT and 11 beta-F-19-nor-DHT to AR are 53.1 and 75.3 (R1881 = 100), respectively, the latter being the highest reported among fluorine-substituted androgens. The fluorination step, which involves addition of halogen fluoride across the 9(11)-double bond, followed by reductive dehalogenation at the 9 alpha-position has been adapted to introduce a fluorine 18-label at the 11 beta-position of DHT and 19-nor-DHT. The two high-affinity F 18-labeled ligands [18F]-1 and [18F]-2 were evaluated in vivo, in tissue distribution studies using diethylstilbestrol-pretreated mature male rats. 11 beta-F-DHT shows high prostate uptake and selective prostate to blood and prostate to muscle uptake ratios, the latter two ratios increasing from 5 and 8 at 1 h to 12 and 19 at 4 h postinjection. Moreover, this compound has low uptake in bone, displaying the lowest in vivo defluorination among all androgens labeled with fluorine-18 tested so far. The in vivo properties of 11 beta-F-DHT in rats are thus favorable for imaging of prostate cancer. On the other hand, 11 beta-F 19-nor-DHT shows low prostate uptake with low selectivity and high uptake in liver, kidney, and bladder. Even though this ligand has the highest RBA and undergoes little metabolic defluorination, it appears to suffer from rapid metabolism in vivo. Therefore, it is apparent that the biodistribution properties of androgens are affected by their structure and metabolism as well as by their RBA. PMID- 7877146 TI - Fluorine for hydroxy substitution in biogenic amines: asymmetric synthesis and biological evaluation of fluorine-18-labeled beta-fluorophenylalkylamines as model systems. AB - This work explores the biomimetic potential of [18F]fluorine for hydroxy substitution in beta-phenethanolamines as a possible strategy for developing radiotracers for in vivo imaging. Stereospecific syntheses of the two model compounds (1R,2S)-1-[18F]fluoro-1-deoxyephedrine ([18F]FDE) and (1S,2S)-1 [18F]fluoro-1-deoxypseudoephedrine ([18F]FDP) were achieved in high radiochemical yield (62%, decay corrected) and high specific activity (> 2500 Ci/mmol) by reaction of [18F]fluoride ion with the appropriate chiral cyclic sulfamidate precursor. Both tracers exhibited good stability toward metabolic defluorination in vivo. High, homogeneous brain uptake (approximately 8% of injected dose) was observed after intravenous injection in mice similar to that reported for the structurally related analog [11C]methamphetamine. The 1R,2S isomer (FDE) showed a 3-fold higher concentration of radioactivity in whole brain as compared to the 1S,2S isomer (FDP). These results suggest possible employment of this strategy for chiral radiolabeling of biologically important phenethanolamines and catecholamines. PMID- 7877148 TI - Synthesis, biological evaluation, and structure analysis of a series of new 1,5 anhydrohexitol nucleosides. AB - In view of the selective anti-HSV activity of 1,5-anhydro-2,3-dideoxy-2- (5 iodouracil-1-yl)-D-arabino-hexitol, a series of novel 1,5-anhydrohexitol nucleosides were synthesized and evaluated for their inhibitory activity against several viruses. The 5-iodouracil 3 and the 5-ethyluracil 4 derivatives are highly selective TK-dependent inhibitors of HSV-1 and HSV-2. Broad anti-herpes virus activity was noticed for 5-fluorocytosine 6 and 2,6-diaminopurine 10 analogues. From a transport study of 3, using the thymidine influx competition method, one can conclude that intracellular uptake of this compound most probably occurs by passive diffusion. X-ray analysis of compounds 3 and 9 showed that the heterocyclic base of 1,5-anhydrohexitol pyrimidine and purine is placed in the axial position and that the sugar ring adopts a slightly distorted chair conformation. PMID- 7877149 TI - Structural and conformational requirements for human calcitonin activity: design, synthesis, and study of lactam-bridged analogues. AB - The conformational and pharmacological effects of the introduction of conformational constraints in the form of i-(i + 4) lactam-bridges in the potential amphiphilic alpha-helical region (8-21) of human calcitonin (hCT) were studied. The following three cyclic hCT analogues were synthesized: cyclo17,21 [Lys17,Asp21]hCT (1), cyclo17,21- [Asp17,Lys21]hCT (2) and cyclo10,14-[Lys10, Asp14]hCT (3). For their syntheses, solid-phase methodology was used in combination with either direct side chain to side chain cyclization on the solid support or a segment-condensation strategy. Circular dichroism studies in aqueous buffer, pH 7.0, indicated that the conformational effects were different for each lactam bridge introduced. Significant induction of alpha-helical structure was observed only for peptide 3. In contrast, peptide 1 and hCT had similar CD spectra, indicative of mixed disordered and beta-sheet conformations, and peptide 2 had a weaker spectrum consistent with the formation of a more ordered but nonhelical structure. In rat brain receptor binding assays, peptide 2 showed a nearly 80-fold higher potency than hCT or peptides 1 and 3. All three analogues stimulated adenylyl cyclase in the rat kidney membrane at 5-fold lower concentrations than hCT and with similar maximal effects. In vivo hypocalcemic assays, performed in mice by analysis of serum calcium levels 1 h after sc injection, indicated that peptide 2 had similar maximal effects to hCT and was 10 20 times more potent than hCT at doses giving half-maximal effects. In contrast, peptides 1 and 3 were not significantly more potent than hCT. Our findings indicate compatibility of all three lactam bridges and, most probably, also the amphiphilic alpha-helix, with the pharmacological activities of hCT. However, the properties of peptide 2 also suggest that another conformation, possibly a type I beta-turn involving residues 17-20, may play an important role. A multistep mechanism of receptor recognition by hCT that might account for these results is discussed. PMID- 7877150 TI - Chemically stable N-methyl-4-(alkylthio)cyclophosphamide derivatives as prodrugs of 4-hydroxycyclophosphamide. AB - Two prototype N-methyl-4-thio-substituted cyclophosphamide (CP) derivatives (5 and 6), prodrugs of 4-hydroxycyclophosphamide (4-HO-CP), were designed to undergo oxidative N-demethylation to release the active alkylating agent. These prodrugs were chemically stable until oxidatively N-demethylated in the presence of hepatic microsomal P-450 enzymes. While the metabolism of 5 was enhanced in the presence of phenobarbital-induced microsomes, 6 was unaffected. Compound 6 was more active than 5 against L1210 leukemia cells grown in mice and exhibited statistically significant activity against the small cell lung cancer panel in the National Cancer Institute anticancer drug screen. Compound 5, like CP (1), was inactive in this screen. Thus, placement of a dithioester at the 4-position of N-methyl-HO-CP as in 6 markedly changes its spectrum of activity and has resulted in a new type of CP-based prodrug with antitumor activity against small cell lung cancer as well as leukemia cells in vitro as shown by their ability to inhibit tumor cell growth at concentrations as low as 10(-6) M. PMID- 7877151 TI - Abnormal expression of intercellular adhesion molecule-1 on peripheral blood mononuclear cells from patients with systemic lupus erythematosus. AB - The expression of intercellular adhesion molecule-1 (ICAM-1) on peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus was observed by flow cytometry. ICAM-1 expression on PBMC was increased in the patients with active disease, and was increased especially on CD5- or CD19+ lymphocytes and monocytes. Furthermore, when B cells were fractionated by Percoll density gradients, ICAM-1 was more expressed on the low- and the intermediate density B cells, which are thought to contain activated B cells, than on the high density B cells, which are thought to contain resting B cells. This might be due to the polyclonal B-cell activation occurring in vivo. Together with the function of B cells and monocytes as antigen presenting cells, this enhanced expression of ICAM-1 on these cells might be associated with the mechanism to maintain the pathophysiology of this disease. PMID- 7877152 TI - Anticardiolipin antibodies in autoimmune thyroid disease. AB - IgG and IgM anticardiolipin antibodies were assayed by an ELISA technique in 69 patients with autoimmune thyroid disease (ATD) and compared with 43 patients with thyroid disease of no autoimmune aetiology (non-ATD) and 72 healthy controls. IgG anticardiolipin antibodies were detectable in 3 of 41 patients with Graves' disease, in 4 of 28 patients with Hashimoto's thyroiditis, in 5 of 43 non-ATD patients and in 3 of 72 normal subjects (differences not significant). IgM antibodies were measurable in 3 patients with Graves' disease, in 1 patient with Hashimoto's thyroiditis, in 1 non-ATD patient and in 2 normal subjects (differences not significant). Patients with anticardiolipin antibodies did not exhibit a higher titre of thyroglobulin or thyroid microsomal antibodies than patients without anticardiolipin antibodies. There was no relation between IgG or IgM anticardiolipin antibody levels and the thyroid function status, the serum concentration of thyroid hormones or thyrotrophin levels. Neither was there any correlation between anticardiolipin antibody levels and age, sex, previous treatments or time of disease progress. Our results suggest that there is no association between anticardiolipin antibodies and ATD. PMID- 7877153 TI - A rapid ELISA for measurement of anti-glomerular basement membrane antibodies using microwaves. AB - The presence of anti-glomerular basement membrane antibodies is one of the features of Goodpasture's syndrome. Since the disease has a rapidly progressive course, an early diagnosis is essential. As was already demonstrated in other ELISA methods, 2.45-GHz microwave irradiation can accelerate all kinds of time consuming processes in several laboratory techniques. The application of microwaves in an ELISA for the measurement of anti-GBM antibodies in serum indicated that a considerable time reduction of 75% can be achieved, resulting in a rapid and reliable assay. In addition, microwaves can also have a positive effect on the resolution of that particular ELISA as shown in this study. PMID- 7877154 TI - Strong synergistic effects of multicomponent vaccine for human immunodeficiency virus infection. AB - Several peptides were synthesized, based on sequences of the HTLV-IIIB, HTLV IIRF, and HTLV-IIIMN strains. These corresponded to the V3 region, the killer T cell activating site, the constant region of env, gag region protein and the helper T cell activating site. Some of these peptides were coupled to keyhole limpet hemocyanin (KLH), and some of them were polymerized with m-maleimido benzoyl-N hydroxysuccinimide ester (MBS). These peptides were used to immunize rabbits and mice. Antisera from immunized animals showed good levels of inhibition of CD4-dependent cell fusion by in vitro HIV infection. The antisera also inhibited the production of p24 protein in the HIV-infected culture system. Interestingly, a strong synergistic HIV growth inhibition by antiserum was observed when we immunized animals with multicomponent vaccine. In addition, substantial levels of HIV antigen-specific IL-2 producing and interferon-gamma (IFN-gamma) producing cells were also observed in lymph node cells from vaccinated mice. These results suggest that immunization with multicomponent vaccine can induce high levels of humoral antibodies as well as activate HIV specific cellular immunity. PMID- 7877156 TI - Stress, depression, and anxiety predict average symptom severity and daily symptom fluctuation in systemic lupus erythematosus. AB - Forty-one subjects diagnosed with systemic lupus erythematosus (SLE) were recruited from across the United States. Regressions were conducted to evaluate the relation among stress, depression, anxiety, anger, and SLE symptom complaints. Negative weighting of major life events predicted symptom history. Significant hierarchical regressions using negative weighting of major life events, impact of daily stress, depression, anxiety, and anger were found for severity of joint pain, abdominal distress, and rash. Analyses using 1-day-lagged predictors yielded similar results. Within-subject analyses suggested that there was much individual variability in the strength of the stress-illness relation. Thus, some individuals appeared to be stress responders, while others did not. Findings for impact of minor life events and depression were consistent across the different levels of analyses. It was concluded that stress, depression, anxiety, and anger are associated with, and may exacerbate, self-reported symptomatology of SLE patients. PMID- 7877155 TI - Health locus of control and psychological distress in cancer patients: interactive effects of context. AB - Delineation of the relationship between health locus of control (HLOC) and psychological adjustment in chronic disease has been hampered by the failure to consider the moderating effect of contextual factors. The extent to which HLOC beliefs match the control realities in a situation (Reality Matching hypothesis) as well as the degree of threat (Threat hypothesis) posed by the situation were hypothesized to moderate the HLOC-distress relationship. Distress, disease severity (i.e., threat), and HLOC were assessed in 69 individuals with malignant disease undergoing evaluation for bone marrow transplantation. Hierarchical regression analyses indicated that the HLOC-distress relationship was moderated by disease severity and treatment history (i.e., whether an individual had failed prior cancer therapy). However, in some instances, the specific interaction relationships obtained differed from those evident in previous research with ESRD patients. It was concluded that there is no simple main effect relationship between HLOC beliefs and psychological adjustment. Rather, this relationship is best described by joint consideration of factors descriptive of the context in which the individual is embedded. PMID- 7877157 TI - Masseter muscle hyperactivity and myofascial pain dysfunction syndrome: a relationship under stress. AB - Myofascial pain dysfunction syndrome (MPD) of the temporomandibular joint (TMJ) is a psychophysiological disorder that develops because of hyperactive muscles of mastication. Ten women meeting criteria for MPD and 12 symptom-free women participated in the study. The rationale for this study was to observe cardiovascular and masseter muscle changes during four contiguous experimental periods: baseline/adaptation, reaction time, recovery, and relaxation. MPD patients showed less masseter muscle activity and higher heart rates at baseline than controls. Controls had significantly higher masseter EMG activity during reaction time. Both groups showed significant elevation in masseter muscle activity and heart rate over the 14-min reaction period. MPD patients' recovery from stress was equivalent to controls' for both heart rate and masseter muscle activity. MPD patients exhibited significantly slower reaction times than controls. The results suggest that masseter muscle hyperactivity may not account for the development and maintenance of MPD. PMID- 7877159 TI - The Pain Anxiety Symptoms Scale: psychometric properties in a community sample. AB - This study investigated the factor structure and psychometric properties of the Pain Anxiety Symptoms Scale (PASS). The PASS assesses four components of pain related anxiety: cognitive, fear, escape/avoidance, and physiological. Confirmatory factor analyses provided support for both the one-factor and the four-factor structures reported for samples of clinic-referred pain patients. The alpha coefficients were high for the PASS subscales. Significant gender differences were obtained on the PASS total and subscale scores. Convergent and divergent validity estimates of the PASS were also assessed. Results may be used to evaluate the responses of clinic-referred pain patients. PMID- 7877160 TI - How compliant is compliant? Evaluating adherence with breast self-exam positions. AB - The present study examined compliance with the three recommended breast self examination (BSE) positions over a 6-month follow-up period. An ongoing behavioral measure that provided information about the type of exam performed during each BSE occasion was employed. Results indicated that adherence to all three position types was obtained in only 40% of the exams. Forty-two percent of exams were comprised of only one position, with the supine position being the most frequently practiced exam type. Implications of these results with regard to BSE research and current breast cancer screening recommendations are discussed. PMID- 7877158 TI - When to measure resting values in studies of children's cardiovascular reactivity. AB - Investigations suggesting that the order of obtaining resting and cardiovascular reactivity measurements moderates values have provided inconsistent results and have not analyzed data from children; the generalizability of results is uncertain. In this investigation, all children enrolled in the eighth-grade classrooms of the public schools of an entire county (n = 451) participated in standardized reactivity assessments. The order of resting and reactivity measurements was randomized by examination day (a total of 19 days). Analyses indicated that all comparisons of order effects on mean resting blood pressure and heart rate, as well as reactivity (both change from resting and absolute values and both mean and maximal values), were nonsignificant. Results indicate that measurement order is not always a necessary consideration in studies of reactivity; the conditions under which measurement order is a consideration requires clarification. PMID- 7877161 TI - Expression, purification and crystallisation of phosphorylase kinase catalytic domain. AB - The catalytic subunit of phosphorylase kinase is composed of a kinase catalytic core domain (residues 1 to 298), which has a 33% identity with the kinase core of the cyclic AMP-dependent protein kinase, and a C-terminal calmodulin binding domain. The kinase domain of the catalytic subunit has been expressed in Escherichia coli, purified and crystallised in the presence of ATP and magnesium from 5% (w/v) polyethylene glycol 8000, 10% (v/v) glycerol, 50 mM Hepes/NaOH (pH 6.9). A three-fold excess of magnesium to ATP was used for crystal growth. The inclusion of glycerol in the crystallization medium produced a marked reduction in mosaic spread of the diffraction spots from greater than 1 degree to 0.3 degree. The crystals are orthorhombic, space group P2(1)2(1)2(1) with unit cell dimensions a = 47.1 A, b = 69.1 A, c = 112.9 A and one molecule per asymmetric unit. Data to 3 A resolution have been collected and structure determination is in progress. PMID- 7877162 TI - An equilibrium partially folded state of human lysozyme at low pH. AB - Temperature-induced unfolding of human lysozyme has been monitored by circular dichroism and by nuclear magnetic resonance experiments at a variety of low pH values. The results indicate that, although at pH values above 3 unfolding appears to be consistent with a two-state model, at lower pH values this is not the case. At pH 1.2, for example, unfolding of the tertiary structure occurs at a temperature approximately 10 deg. C lower than that of the secondary structure. At 60 degrees C there is no detectable native tertiary structure remaining for human lysozyme at pH 1.2, although far-UV CD results show preservation of some 40% of the signal attributable to alpha-helical elements in the protein. This indicates the existence of a partially folded state of human lysozyme at low pH that has at least some characteristics of the well-defined molten globule state of the homologous alpha-lactalbumins and of the kinetic intermediates observed in the folding of alpha-lactalbumins and of c-type lysozymes. These results suggest that the absolute distinction between these two groups of proteins in terms of their different unfolding behaviour is not valid, and provide insights into possible features stabilizing such states. PMID- 7877163 TI - Partition functions of mini-F affect plasmid DNA topology in Escherichia coli. AB - Efficient segregation of the low copy number plasmid mini-F is dependent on partition functions encoded by the plasmid sopABC genes. The sop region encodes proteins SopA and SopB and a cis-acting element, sopC, which may function as a centromere analog. The SopC segment contains 12 imperfect 43 bp repeats to which the SopB protein binds. We have found that mutations in the sop genes affect superhelicity of isolated plasmid DNA. Plasmids with mutations in sopB or a deletion of the sopC segment were more highly negatively supercoiled than normal. In contrast, a mutation in the autoregulatory SopA protein resulted in plasmid DNA that was more relaxed. The SopAB proteins provided in trans to a pBR322 plasmid carrying sopC resulted in the relaxation of negative supercoils. We suggest that binding of SopB protein to the cis-acting sopC segment in vivo, alone or in conjunction with other proteins, produced a change in DNA topology in which positive superhelical turns were introduced locally. This higher-order nucleoprotein structure may allow interaction of plasmid mini-F with the partition apparatus. PMID- 7877164 TI - Ancestral, mammalian-wide subfamilies of LINE-1 repetitive sequences. AB - Analysis of the 3'-ends of approximately 900 separate human LINE-1 (L1) elements from primates revealed 47 contiguous but distinct subfamilies with the L1 family. Eight previously described medium reiteration frequency sequences (MERs) were found to be parts of ancient L1 untranslated 3'-regions which show little or no sequence similarity to the presently active L1 3'-end. Some of the major changes in 3'-end sequence can be explained by recombination events between different L1 repeats as well as between L1 and unrelated repetitive sequences. One of these sequences, MER42, is reported in this paper. With the set of consensus sequences for different subfamilies and their diagnostic features, it is possible to estimate the age of individual LINE-1 elements. Contrary to earlier suggestions, the majority of L1 copies in the human genome is very old; more than half of the identifiable elements were inserted into the genome before the mammalian radiation, as evidenced by elements at orthologous sites in human and other mammalian genomes. Multiple distinct L1 source genes seem to have been active simultaneously over long periods of time. PMID- 7877165 TI - In vitro packaging of the single-stranded RNA genomic precursors of the segmented double-stranded RNA bacteriophage phi 6: the three segments modulate each other's packaging efficiency. AB - Bacteriophage phi 6 is a double-stranded RNA (dsRNA) virus that has a genome composed of three linear dsRNA segments (l, m, s). These are encapsidated into a dodecahedral procapsid particle consisting of proteins P1, P2, P4 and P7. Expression of the cDNA copy of the L segment in Escherichia coli leads to the formation of empty procapsid particles. These particles are able to package the plus-sense single-stranded RNA (ssRNA)s of each genome segment in vitro. We have used this in vitro system for a detailed study of phi 6 RNA packaging. The reaction conditions for RNA packaging were optimized using a RNase protection assay. The RNA packaging reaction is dependent on divalent cations (either Mg2+ or Mn2+) and requires a nucleoside triphosphate (NTP) as an energy source. Any one of the rNTPs, dNTPs or ddNTPs can support the RNA packaging. Purine nucleotides support packaging better than pyrimidine nucleotides, GTP being preferred to ATP. The plus-sense ssRNA of each the three genome segments can be packaged independently into the procapsid. However, when two or three segments are packaged simultaneously, regulatory effects modulating the packaging efficiency can be detected between the segments. The packaging of the s and m segments is more efficient when they are packaged alone, compared to a situation in which they are packaged with the other segments. In contrast, the packaging of the l segment is very inefficient alone, but is enhanced when packaged together with the m segment. We propose that each segment has a preferred high-affinity binding site in the procapsid particle and packaging of the m segment creates the high-affinity binding site for the l segment. If any of the segments is missing from the packaging reaction the other segments can occupy its binding site. PMID- 7877166 TI - Crystallographic refinement at 2.3 A resolution and refined model of the photosynthetic reaction centre from Rhodopseudomonas viridis. AB - The atomic model of the photosynthetic reaction centre from the purple bacterium Rhodopseudomonas viridis has been refined to an R-value of 0.193 at 2.3 A resolution. The refined model contains 10,288 non-hydrogen atoms; 10,045 of these have well defined electron density. A Luzzati-plot indicates an average co ordinate error of 0.26 A. During refinement, the positions of a partially ordered carotenoid, a unibiquinone in the partially occupied QB site, a detergent molecule, seven putative sulphate ions, and 201 water molecules were found. More than half of these waters are bound at interfaces between protein subunits and therefore contribute significantly to subunit interactions. Water molecules also play important structural and probably functional roles in the environment of some of the cofactors. Two water molecules form hydrogen bonds to the accessory bacteriochlorophylls and to the protein in the vicinity of the special pair of bacteriophylls, the primary electron donor. A group of about 10 water molecules is bound near the binding site of the secondary quinone QB. These waters are likely to participate in the transfer of protons to the doubly reduced QB. PMID- 7877167 TI - The bacteriophage N4-coded single-stranded DNA-binding protein (N4SSB) is the transcriptional activator of Escherichia coli RNA polymerase at N4 late promoters. AB - Transcription of the 72kb linear double-stranded DNA genome of coliphage N4 is carried out by the sequential activity of three different RNA polymerases. Early and middle viral transcripts are synthesized by two phage-coded RNA polymerases while late transcription is carried out by the Escherichia coli sigma 70-RNA polymerase. We have determined the sequences and sites of initiation of several N4 late transcripts; N4 late promoters share weak homology with the E. coli sigma 70 promoter consensus sequence. Indeed, N4 late promoters are weak templates for the host enzyme. We present evidence that the phage-coded, single-stranded DNA binding protein (N4SSB), a protein that is required for phage DNA replication and recombination and does not bind with sequence specificity to DNA, is the activator of E. coli RNA polymerase at late N4 promoters. Models for the mechanism of action of N4SSB as a transcriptional activator are discussed. PMID- 7877168 TI - A model for copy number control of the plasmid R1. AB - A new model for copy number control of the plasmid R1 has been developed. It takes into account that initiation of replication of R1 requires a large number of cis-acting proteins (RepA). The theory explains how plasmid production rates respond to shifts in external conditions. It predicts the observed "eclipse" times between two plasmid duplications as well as the replication time for "runaway" plasmids lacking the antisense inhibitor CopA. The model also describes how the use of many cis-acting RepAs can lead to a tight coupling between cell and plasmid cycles that minimizes the rate of the plasmid loss. The results may be used as a guideline for construction of low copy number plasmids with high maintenance stability. PMID- 7877169 TI - Visualization of large DNA molecules by electron microscopy with polyamines: application to the analysis of yeast endogenous and artificial chromosomes. AB - Standard visualization of nucleic acids by electron microscopy requires the use of special spreading techniques. The most common method takes advantage of the formation of a complex between negatively charged nucleic acid molecules and a positively charged monolayer film of proteins or cationic agents. Here, we describe an alternative protocol for the rapid visualization of DNA by electron microscopy based on the complexes formed when nucleic acids are exposed to buffers containing polyamines in the presence of sodium chloride. This procedure has been devised for the detection and analysis of large DNA molecules, such as yeast artificial chromosomes, but can be applied to DNA molecules of small size as well. The formation of DNA-polyamine complexes stabilizes large DNA molecules in solution and prevents shearing. This property allows large DNA molecules to remain intact after passage through microcapillaries used in the generation of transgenic mice by microinjection of fertilized eggs. PMID- 7877170 TI - Mechanism of photosensory adaptation in Halobacterium salinarium. AB - Phototaxis in Halobacterium salinarium is the result of an interplay of sensory rhodopsin excitation and adaptation to the stimulus background. Adaptation to orange light, received by sensory rhodopsin I was probed by measuring the behavioral response of cells to a step-like decrease in intensity. Cells were able to adapt to an intensity range of more than four orders of magnitude. The data were analysed on the basis of theoretical fluence rate response relationships calculated from the photocycle kinetics of the complex of sensory rhodopsin I with its transducer HtrI. Independent of the stimulus background, the cellular response was shown to be a function of the absolute number of photoreceptor complex molecules turned over by the light stimulus. Receptor deactivation was identified as the underlying mechanism of adaptation and was sufficient to account for the experimental results. We suggest that reversible methylation of the transducer protein HtrI provides the chemical mechanism of sensory adaptation in H. salinarium and also explains the different sensitivity of the cells to orange and UV light. PMID- 7877171 TI - Beta-tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. AB - Resistance to antimitotic chemotherapeutics in pathogenic nematodes, fungi and mammalian cells is closely associated with structural changes in cytoskeletal beta-tubulin. We investigated the possibility of using the well-characterised free-living nematode Caenorhabditis elegans as a model for studying the mechanism of resistance against benzimidazole (BZ) drugs in the parasitic nematode Haemonchus contortus. Functional analysis of a conserved beta-tubulin isotype (tub-1) mutation near GTP-binding domain II, which is linked to BZ resistance, was carried out in C. elegans by heterologous expression of: (1) parasite BZ sensitive alleles; (2) BZ-resistant alleles; and (3) in vitro mutagenised beta tubulin gene constructs. The injected heterologous gene constructs were not only stably maintained, but also expressed as shown by reverse transcriptase polymerase chain reaction analysis. The degree of BZ drug susceptibility of the transformants was assayed and quantified by incubation with both benomyl and thiabendazol. All H. contortus tub-1 constructs, which encoded Phe at position 200, conferred susceptibility to thiabendazole in BZ-resistant C. elegans ben-1 mutants. In contrast, constructs carrying Tyr200 did not alter the BZ drug phenotype. From these experiments we conclude that: (1) C. elegans can be used as an expression host, since injected parasite genes were biologically active; and (2) the single Phe to Tyr mutation at position 200 in beta-tubulin isotype 1 is the cause of BZ resistance in H. contortus. PMID- 7877172 TI - The crystal structure of holo-glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic bacterium Thermotoga maritima at 2.5 A resolution. AB - The crystal structure of holo-glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophile Thermotoga maritima was determined by Patterson search methods using the known structure of the Bacillus stearothermophilus enzyme. The structure was refined at a resolution of 2.5 A to an R-factor of 16.63% for 26289 reflections between 8.0 A an 2.5 A with F > 2 sigma(F). The crystallographic asymmetric unit contains two monomers related by approximate 2-fold symmetry and a tetramer is built up by crystallographic symmetry. The root-mean-square deviation of Ca positions of glyceraldehyde-3-phosphate dehydrogenase from T. maritima and B. stearothermophilus is 0.83 A in the NAD+ binding domains and smaller close to the cofactor. In contrast, the largest deviations in the catalytic domains are found at residues involved in coordination of sulphate ion SO4 339, which most likely marks the site of the attacking inorganic phosphate ion in catalysis. A large number of extra salt-bridges may be an important factor contributing to the high thermostability of this protein. PMID- 7877173 TI - Substrate specificity and assembly of the catalytic center derived from two structures of ligated uridylate kinase. AB - Two crystal structures of ligated uridylate kinase from Saccharomyces cerevisiae were determined by X-ray analyses. The ligands were ADP and AMP. Cocrystallization with ATP yielded crystals with ADP at the ATP site and a mixture of AMP and ADP at the NMP site. Cocrystallization with ADP gave rise to a distinct crystal type with ADP at the ATP site, but only AMP at the NMP site. In both cases, the substrates are kept in place by favorable crystal contacts. The structures have been refined to R-factors of 17.8% and 19.6% at resolutions of 2.1 A and 1.9 A, respectively. A comparison with the related cytosolic adenylate kinase from pig disclosed large induced-fit movements on substrate binding and the disassembly of the catalytic center in the absence of substrates. The relatively high side-activity of uridylate kinase for AMP is explained by the finding that the binding pocket is sized for an AMP, but constructed to bind UMP together with a water molecule. PMID- 7877174 TI - X-ray structure analysis of the iron-dependent superoxide dismutase from Mycobacterium tuberculosis at 2.0 Angstroms resolution reveals novel dimer-dimer interactions. AB - The X-ray structure of the tetrameric iron-dependent superoxide dismutase from Mycobacterium tuberculosis has been refined to an R-factor of 0.167 and a correlation coefficient of 0.954 at 2.0 A resolution. The crystals are monoclinic P2(1) and have four subunits related by strong non-crystallographic 222 (or D2) symmetry in the asymmetric unit. 198 of the 207 amino acids of each subunit are defined by the electron density which shows that they adopt the conserved fold of other iron- or manganese-dependent SODs. The structure can be divided into two domains, the N-terminal domain involving an extended region followed by two projecting antiparallel alpha-helices, and the C-terminal domain containing four more helical segments with a three-stranded antiparallel beta-sheet inserted sequentially between the fourth and fifth helices. The catalytic iron is co ordinated by five ligands: three histidines (residues 28, 76 and 164), one aspartate (160) and a solvent molecule. The inferred positions of protons at the active site are consistent with the solvent ligand being a hydroxide ion. This ligand interacts with His145 in the Mycobacterium tuberculosis SOD. In the highly homologous Mycobacterium leprae Mn-SOD, the histidine is replaced by glutamine, this being the only significant residue difference within 10 A of the Fe3+. The nature of the amino acid at this position may influence the metal ion specificity of these enzymes. The subunits of the Mycobacterium tuberculosis SOD associate by polar contacts to form dimers, which closely resemble those of other dimeric or tetrameric Fe- or Mn-SODs. However, the dimer-dimer interactions within the tetramer are novel, being dominated by dimerisation of the 144 to 152 loop regions which connect the outer two beta-strands of the three-membered beta sheet. This contrasts strongly with the other tetrameric Fe- or Mn-SODs where the dimer-dimer association is dominated by the projecting alpha alpha-turn in the N terminal domain. PMID- 7877175 TI - Crystal structure of calcium-depleted Bacillus licheniformis alpha-amylase at 2.2 A resolution. AB - The three-dimensional structure of the calcium-free form of Bacillus licheniformis alpha-amylase (BLA) has been determined by multiple isomorphous replacement in a crystal of space group P4(3)2(1)2 (a = b = 119.6 A, c = 85.4 A). The structure was refined using restrained crystallographic refinement to an R factor of 0.177 for 28,147 independent reflections with intensities FObs > 0 at 2.2 A resolution, with root mean square deviations of 0.008 A and 1.4 degrees from ideal bond lengths and bond angles, respectively. The final model contains 469 residue, 237 water molecules, and one chloride ion. The segment between Trp182 and Asn192 could not be located in the electron density, nor could the N and C termini. Cleavage of the calcium-free form of BLA was observed after Glu189, due to a Glu-C endopeptidase present in trace amounts in the preparation. BLA did not crystallize without this cleavage under the conditions applied. BLA exhibits the characteristic overall topological fold observed for other alpha amylases and related amylolytic enzymes: a central domain A containing an alpha/beta-barrel with a large protrusion between beta-strand 3 and alpha-helix 3 (domain B) and a C-terminal greek key motif (domain C). Unlike in the other enzymes, domain B possesses a beta-sheet made up of six loosely connected, twisted beta-strands forming a kind of a barrel with a large hole in the interior. Topological comparisons to TAKA-amylase, pig pancreatic alpha-amylase and cyclodextrin glycosyltransferase reveal a very high structural equivalence for large portions of the proteins and an exceptionally pronounced structural similarity for calcium binding, chloride binding and the active site. None of the theories proposed to explain the enhanced thermostability of BLA showed a satisfactory correlation with the three-dimensional structure. Instead, sequence comparisons to the less thermostable bacterial alpha-amylase from Bacillus amyloliquefaciens (BAA) indicate that some ionic interactions present in BLA, but which cannot be formed in BAA, might be responsible for the enhanced thermostability of BLA. PMID- 7877176 TI - A hybrid sigma subunit directs RNA polymerase to a hybrid promoter in Escherichia coli. AB - Most of the sigma (transcriptional initiation specificity) subunits of RNA polymerase, from a wide range of eubacteria, show strong elements of amino acid sequence similarity. There is evidence that two of the "conserved" regions, 2.4 and 4.2, are involved in recognition of the consensus DNA sequences centred near 10 and -35, respectively, which define promoter sites for the initiation of transcription. Since all the alternative sigma subunits of the above type function by binding to a common core polymerase enzyme in a given bacterium, it can be predicted that a hybrid sigma might be functional, and if so should permit RNA polymerase to initiate only at a correspondingly hybrid promoter. To test these predictions, a hybrid gene encoding the amino-proximal 529 amino acids of the major Escherichia coli sigma protein, sigma 70 (including region 2.4) followed by the last 82 amino acids of the heat-shock sigma protein, sigma 32 (including region 4.2) was constructed and fused to Plac on a plasmid. Major consensus, heat-shock and hybrid promoters were fused to a chloramphenicol acetyl transferase (CAT) reporter gene on a compatible plasmid. CAT assays showed that, as predicted, a promoter with a "heat-shock" -35 consensus and a "major" -10 consensus sequence (PHM) required Plac-dependent production of the hybrid sigma (sigma 70-32) for activity in vivo. PHM then became a strong promoter. The hybrid sigma gene has potential advantages over its parents for structure-function studies. PMID- 7877177 TI - Effects of ethyleneglycol chain length of dodecyl polyethyleneglycol monoether on the crystallization of bovine heart cytochrome c oxidase. AB - Tetragonal crystals that diffracted X-rays up to 5 A resolution were obtained from bovine heart cytochrome c oxidase isolated and solubilized with dodecyl octaethyleneglycol monoether, CH3(CH2)11O(CH2CH2O)8H. Comparison of observed structure factors between data sets each obtained from a different native crystal gave correlation coefficients of 0.92, 0.84 and 0.57 at 10 A, 7 A and 6 A resolution, respectively. The space group and the cell dimensions of the crystal are I4(1) or I4(3) and a = b = 253 A, c = 507 A, respectively. The perfection and stability of the tetragonal crystals are significantly higher than those of the hexagonal crystals of the protein stabilized with Brij-35, CH3(CH2)11O(CH2CH2O)23H (whose details are reported elsewhere). Examination of the effect of ethyleneglycol chain length on the crystallization revealed that only dodecyl polyethyleneglycol monoethers with eight and seven units were appropriate for producing this type of crystal, indicating an optimum size of the detergent for crystallization of the membrane protein. PMID- 7877178 TI - IS10 antisense control in vivo is affected by mutations throughout the region of complementarity between the interacting RNAs. AB - Translation of the IS10 transposase mRNA (RNA-IN) is inhibited by antisense pairing with a small IS10 encoded transcript called RNA-OUT. To further characterize IS10 antisense control, an extensive set of mutations in the region of complementarity between RNA-OUT, and its target RNA-IN have been isolated. These mutations have been characterized for their effects on antisense inhibition of transposase gene translation in vivo. Mutations that confer the strongest defects on translational inhibition are found in the region corresponding to the 5' end of RNA-IN. However, mutations throughout the complementary region affect antisense control regardless of whether mutations are present in RNA-IN alone or as complementary mutations in both RNAs. An analysis of the data presented here suggests that in vivo pairing rates for the wild-type antisense species are very close to being optimal. Some of the motifs found in antisense molecules that may be associated with efficient pairing rates are discussed. PMID- 7877179 TI - Determination of the binding sites of RepA, a replication initiator protein of the basic replicon of the IncN group plasmid pCU1. AB - A 2kb DNA region of the broad-host-range plasmid pCU1 carries all of the information essential for the stable maintenance of the plasmid and to express the same host-range specificity. It was predicted that the protein required to initiate replication from at least one of the three origins of the plasmid is encoded by the longest open-reading frame (ORF239) of the three overlapping in frame ORFs located within the 2 kb region. The product of ORF239 has been named RepA. The initiator protein was overexpressed, purified and used for in vitro binding studies. Gel mobility shift experiments were performed to localize RepA binding sites. The DNA sequence protected by the bound RepA molecule(s) was determined by DNase I footprinting and 19 of a 20 bp long sequence that is part of the protected sequence were located in two clusters flanking the repA gene. A plasmid created by linking a 310 bp fragment (nucleotides 238 to 547) of the 2 kb region to the antibiotic resistance genes carried by the omega fragment, can be maintained stably if the RepA protein is supplied in trans. We conclude that this 310 bp DNA fragment, which consists of a short G+C and a long A+T rich region and the cluster of five RepA binding sites, carries a functional origin of the plasmid-protein dependent replication. The position of this origin indicates that it is oriB, one of the three origins previously identified by electron microscopy. The second cluster of RepA binding sites is downstream of the repA gene and consists of 14 sites that are in inverted orientation compared with the binding sites located in the oriB region. They are part of the region that was shown formerly to be involved in controlling the copy number of the plasmid. In contrast to oriB, binding of RepA to neither the oriS nor oriV region was detected. PMID- 7877180 TI - Solution dynamics of the trp repressor: a study of amide proton exchange by T1 relaxation. AB - The amide proton exchange rates of Escherichia coli trp repressor have been measured through their effects on the longitudinal relaxation rates of the amide protons. Three types of exchange regimes have been observed: (1) slow exchange (on a minute/hour time-scale), measurable by isotope exchange, but not by relaxation techniques in the core of the molecule; (2) relatively rapid exchange, with the rates on a T1 relaxation time-scale (seconds) in the DNA-binding region and (3) very fast exchange at the N and C termini. The results have been analyzed in terms of the two-site exchange model originally proposed by Linderstrom-Lang, and of a three-site extension of the model. The values of the intrinsic exchange rates calculated using the two-state model agree with the values expected from the studies of Englander and co-workers for the very fast case of the chain terminals, but disagree with the literature values by two orders of magnitude in the intermediate case found in the DNA-binding region. The implication of these findings is that the "open" state of the two-state model in the DNA-binding region is not completely open and has an intrinsic exchange rate different from that of a random coil peptide. Alternatively, if the literature values of the intrinsic exchange rates are assumed to apply to the open states in all parts of the repressor molecule, two "closed" helical states have to be postulated, in slow exchange with each other, with only one of them in rapid exchange with the open state and hence with the solvent. Kinetically, the two models are indistinguishable. PMID- 7877181 TI - Beta-tubulin folding is modulated by the isotype-specific carboxy-terminal domain. AB - To investigate the contribution of the carboxy-terminal domain in the process of tubulin folding and dimer formation, we constructed a beta 1-beta 3 tubulin chimaera and two truncated carboxy-terminal beta 3-tubulins. The capacity of these altered polypeptides to incorporate into dimers and into microtubules was tested by non-denaturing electrophoresis and co-assembly experiments. The chimaera and the truncated protein with a deletion encompassing the last 12 amino acid residues (beta 3 delta C12) were incorporated into dimers and microtubules, though the level of incorporation was diminished compared to wild-type beta 3 tubulin. However, the level of incorporation of beta 3 delta C12 into subtilisin digested dimers was similar to the incorporation of wild-type beta 3-tubulin. Since subtilisin deletes the carboxy-terminal region, these results suggest a regulatory role of the carboxy-terminal region in the folding process itself and not in the formation of the dimer. PMID- 7877182 TI - Surface morphology of hamster (Mesocricetus auratus) decidual cells in vitro. AB - Cell surface morphology of hamster decidual cells isolated from day 8 implantation swellings was studied, using both phase-contrast and scanning electron microscopy. Two kinds of cells, fibroblastic and epithelioid, were identified in cultures examined by phase-contrast microscopy. Fibroblastic cells were spindle-shaped, having pointed or blunt terminals on one end and bifid or webbed projections at the other end. Epithelioid cells, on the other hand, were flat and discoid, having a distinctively ruffled plasma membrane. Further, the plasma membrane of epithelioid cells formed rope-like or flange-like processes. The significance of such adaptations is discussed. PMID- 7877183 TI - Ultrastructure of the ventral sucker of Schistosoma mansoni cercaria. AB - The ventral sucker of Schistosoma mansoni cercaria is a cup-shaped structure that is attached to the ventral surface of the organism by a homogeneous connective tissue that surrounds the acetabular glands. The sucker consists of an extensive complex of circular and longitudinal muscles. The longitudinal muscles extend outward in a radial pattern to form the cup of the organ. Intermingled with the muscles are nerve bundles and subtegumental cells (cytons). Dendritic nerve fibers connect to sensory papillae which are found on the surface tegument. Two types of sensory papillae are present: a commonly found unsheathed uniciliated papilla, and a previously unidentified tegumental encapsulated structure. Tegument with spines covers the ventral sucker, although the tegumental encapsulated sensory papilla lacks spines. PMID- 7877184 TI - Anatomy of neurons crossing the tritocerebral commissures of the cockroach Periplaneta americana (Blattaria). AB - The neuronal connections of the tritocerebral commissures of Periplaneta americana were studied in the brain-suboesophageal ganglion complex and the stomatogastric nervous system by means of heavy metal iontophoresis through cut nerve ends followed by silver intensification. The tritocerebral commissure 1 (Tc1) contains mainly the processes of the subpharyngeal nerve (Spn) whose neurons are located in both tritocerebral lobes and in the frontal ganglion. Some neurons of the frontal ganglion project through the Tc1 to the contralateral tritocerebrum. A few fibers in this commissure were observed projecting to the protocerebrum and the suboesophageal ganglion. There are tritocerebral neurons which pass through the Tc1 or the tritocerebral commissure 2 (Tc2) and extend on into the stomatogastric nervous system. One axon of a descending giant neuron appears in the Tc2. This neuron lies in the tritocerebrum and connects the brain to the contralateral side of the ventral nerve cord. In addition, sensory fibers of the labral nerve (Ln) traverse both commissures to the opposite tritocerebrum. The anatomical and physiological relevance of the identified neuronal pathways is discussed. PMID- 7877185 TI - The utero-placental circulation, eugenics and the prevention and treatment of high risk pregnancies. AB - Through systematic experimental and clinical studies, the physiological regulation of utero-placental circulation and the relation of the disturbance in this acirculation to pathogenic mechanisms of high risk pregnancies-Intrauterine Growth Retardation (IUGR) and Pregnancy-induced hypertension (PIH) were explored. The pharmacological effects and mechanism of a Chinese herbal medicine Qingxintong in improving, the utero-placental circulation and the therapeutic efficacy in treatment of IUGR and PIH, both accompanied by disturbance of utero placental circulation, were investigated as well. PMID- 7877186 TI - Experimental study on anti-tumor effect of splenocytes induced by anti-CD3 McAb, PHA and IL-2. AB - The proliferation of splenocytes from healthy adults was induced by anti-CD3 McAb, PHA and IL-2. The proliferative capability and anti-tumor activity as well as phenotypes of the splenocytes cultured in different medium systems were studied. The results showed that anti-CD3 McAb and PHA not only enhanced the proliferation of splenocytes induced by IL-2, but also produced synergism if used simultaneously. The expressions of CD4 and Tac of cellular surface markers were increased after splenocytes were induced by anti-CD3 McAb and PHA. The results of anti-tumor activity of LAK cells suggested that PHA had the capability to promote anti-tumor activity of LAK cells by both direct and indirect pathways, but anti CD3 McAb indirectly promoted anti-tumor activity of LAK cells by enhancing splenocyte proliferation. PMID- 7877187 TI - The production of strains highly expressing human interleukin-2 cDNA. AB - The plasmid pTLIL-2, which only directed a low-level expression of human interleukin 2(IL-2) cDNA in E. coli, was reconstructed: a series of deletions were made in 3' non-coding region of human IL-2 cDNA, and 7 recombinant plasmids with different deletions were selected, on the other hand, a Tac promoter sequence from pDR540 was inserted to upstream of IL-2 cDNA in pTLIL-2 so that pTLIL-2DT, which contains double Tac promoters, was constructed. And then, E. coli JM103 was transformed with the above 8 recombinant plasmids respectively. The expression efficiency of IL-2 cDNA in E. coli transformed with different plasmids was evaluated by means of SDS-PAGE and measuring 3H-TdR incorporation of IL-2-dependent activated T lymphocytes in the presence of bacterial extracts. Three engineering strains with high efficiency of IL-2 expression were selected, and all of these strains could produce recombinant IL-2(rIL-2) 4 times more than E. coil JM103/pTLIL-2. PMID- 7877188 TI - Preliminary study on bcr rearrangement in leukemia. AB - Southern blot analysis was conducted in 15 patients by using a 1.2 Kb Hind III/Bgl II fragment from the 3' end of the bcr region and a 2.0 Kb Bgl II/Hind III fragment from the 5' end of the bcr as probes. Of the 15 patients in our group, 11 with chronic, myelocytic leukemia (CML), 3 with Ph-negative acute lymphocytic leukemia (ALL), one with myelodysplastic syndrome (MDS). Bcr rearrangements were detected in 9 patients with CML and were negative in the rest of the patients. The results showed that the identification of bcr rearrangement was very important in the diagnosis of Ph-positive leukemias. PMID- 7877189 TI - A research on DLA-DRB1 genotyping by PCR-RFLP. I. To select a appropriate oligonucleotide primer pair. AB - In order to study the DLA (Dog Leucocyte Antigen) class II region we utilized the polymerase chain reaction based restriction fragment length polymorphism (PCR RFLP) method, which has been reported previously as an efficient and simple technique for accurate definition of the HLA class II alleles. To search for a appropriate primer pair a series of amplifications with 4 different primer pairs DLA-DR-SP/Stop, DLA-DR-SP/P3, HLA-DRB-GH46/50 and HLA-DRB-AMP-A/B were provided. Only one satisfactory amplification was obtained with the primer pair HLA-DRB-AMP A/B. The analogous sequences of the primer pair are found in the sequence of HLA DRB-cDNA. The amplification region of the primer pair includes also the three hypervariable regions (HVR) in the sequence of DLA-DRB cDNA. Southern blot hybridization analysis confirmed the specificity of the primer pair HLA-DRB-AMP A/B. The results of Hae III and Hinfl digestion show high polymorphism in DLA-D region and allele specific polymorphic patterns. Therefore, it is suggested that the primer pair HLA-DRB-AMP-A/B is at present the only available and usefull primer pair in PCR-RFLP study of DLA-DRB1 gene. PMID- 7877190 TI - Researches on DLA-DRB1 genotyping by PCR-RFLP. II. A study of serology and cellularly defined DLA haplotypes and their segregation. AB - The polymerase chain reaction based restriction fragment length polymorphism (PCR RFLP) method was used to study DLA class II gene in dogs. Genomic DNA from 11 DLA homozygous reference dogs representing 8 different haplotypes and 2 families with a total of 16 animals were amplified by the oligonucleotide primer pair (HLA-DRB AMP-A/B) cross-hybridizing HLA-DRB specific and fit for the amplification of DLA DRB1 gene. The corresponding amplified DNA products were 235 base pairs. Amplified DNA was digested by 32 different restriction endonucleases, which could recognize allelic variations within DLA-DRB. After digesting only with Hae III, Hha I, Hinf I, Rsa I and Sau96 I high polymorphism was revealed respectively and 9 distinct RFLP pattern were shown, which could be correlate to the DLA haplotypes studied. The 8 cellular established DLA-D specificities present in the reference panel were defined unequivocally by PCR-RFLP and correlated with DLA Dw5 and Dw6 two subtypes. The segregation pattern of four different DLA-DRB types could be demonstrated in two families. Based on these data we conclude that PCR RFLP typing utilizing the above mentioned primer pair and endonucleases is a valuable tool to define DLA class II types in the dog. PMID- 7877191 TI - A chromosome study on 97 cases of acute nonlymphocytic leukemia M2. AB - Chromosomal studies were performed in the same laboratory on 97 untreated cases of de novo acute nonlymphocytic leukemia M2. The overall incidence of chromosomal abnormality was 70.1% (68 out of 97 cases), which was higher in children (84.2%) than in adults (61%). The male to female chromosomal abnormality ratio was nearly the same (male 71% and female 68.4%, P > 0.05). Hypodiploidy was the most common numerical abnormality (39%) and t (8; 21) was the most common structural abnormality (48.1%). In the patients with t(8; 21), 64.5% (20 out of 31 cases) male lost chromosome Y (-Y) and 33% (5 out of 15 cases) female lost one chromosome X (-X). PMID- 7877192 TI - The morphological studies on M2/t(8; 21) acute nonlymphocytic leukemia. AB - Bone marrow studies including morphological, morphometrical and ultrastructural aspects were performed in 35 patients with M2/t(8; 21) and 23 patients with M2/NN. It was found that M2/t(8; 21) patients had higher cellularity in bone marrow. Type (II) myeloblast cells were predominant among myeloblasts. Deformation of nuclei, nucleocytoplasmic asynchronism and dysmegakaryocytopoiesis were more evident in M2/t(8; 21) than in M2/NN patients. PMID- 7877193 TI - ATP evokes calcium transients in single pulmonary artery endothelial cell in primary cultures. AB - Effects of ATP on cytosolic free calcium ([Ca2+]i) in single porcine pulmonary artery endothelial cell were studied. Using a dual-wavelength excitation microflurometry, it was found that ATP evoked a rapid transient in [Ca2+]i which was then followed by a maintained elevation of [Ca2+]i. The removal of extracellular Ca2+ abolished the maintained plateform, but exerted no obvious effect on the initial-transient. These results suggest that ATP stimulates both calcium release from intracellular calcium pool(s) and calcium influx across the plasma membrane from extracellular space. PMID- 7877194 TI - Effects of captopril and nadolol on renal hemodynamics in patients with essential hypertension. AB - The randomized single-blind study was designed to compare the effects of captopril (Cap) and nadolol (Nad) on renal hemodynamics in 60 patients with essential hypertension. They were divided into two groups at random. Cap was given in dosage of 37.5-75 mg/d per os and Nad 40-80 mg/d. The results show that both drugs increase the blood volume distributed to the kidneys from cardiac output (renal blood flow/cardiac output), Cap increasing 10% (P < 0.05) and Nad 8% (P < 0.05). Renal vascular resistance (RVR) is lowered by the two drugs, 13% (P < 0.05) by Cap and 11% (P < 0.05) by Nad. These suggest that both drugs facilitate the maintenance of renal blood circulation in patients with essential hypertension, being beneficial for long-term treatment of hypertension. PMID- 7877195 TI - The effect of andrographis paniculata nees (APN) in alleviating the myocardial ischemic reperfusion injury. AB - In experimental dogs, the effect of APN in alleviating the ischemia-reperfusion injury was prominent. Compared with the sustained ischemia group, superoxide dismutase (SOD) in the ischemic region of myocardial tissue in the ischemia reperfusion group was significantly decreased and malondialdehyde (MDA) markedly increased: Ca2+ in myocardial cells was increased; and ultrastructural changes of myocardial tissues were severe. In the APN-pretreated ischemia-reperfusion group, on the contrary, all the above parameters showed reversely, i.e., SOD increased, MDA and intracellular Ca2+ decreased, the ultrastructure changes were less distorted. PMID- 7877196 TI - An experimental study on the disturbance of liver circulation and the change of hemorrheology in dogs with acute liver damage. AB - The changes of hepatic hemodynamics and hemorrheology were investigated in dogs with acute liver damage induced by acetaminophen. There were remarkable disturbance in liver circulation and hemorrheological abnormality occurring in both slight and severe liver damage. The study indicated that the degree of disturbance in liver circulation as well as in hemorheological change is positively correlated with the severity of liver damage. For example, marked increase in blood viscosity linked with elevated fibrinogen level appeared in slight liver damage, whereas reduced blood viscosity associated with decreased plasma fibrinogen level and hematocrit occurred in severe liver damage. This study also revealed that the increase of portal venous resistance (PVR) and the disturbance of liver circulation in slight liver damage were chiefly related to the increase of blood viscosity and the increase of PVR in severe liver damage was mainly associated with the reduction of the radius of portal vein. PMID- 7877197 TI - Multi-variate stepwise discriminant analysis research affecting portal hypertension's grade factors of liver function. AB - The ideal time for selecting portal hypertension operation is the accurate judgement of the grade of liver function, yet the present criterion in grading liver function is controversial. 50 patients with 20 factors related to portal hypertension were undergone stepwise discriminant analysis by using SAS software on the IBM/PC computer (significance level alpha = 0.05). The results show that ascites degree prothrombin time (PT), serum total bilirubin, serum albumin content, main portal vein flow are significant factors. In the light of above variates contributing to grading liver function as to establish a discriminant equation, it was found that the total agreement rate between replaceable discrimination and original Child-Pugh classification is 86%. A test for agreement was performed between discriminant and original classification, showing that the two kinds of classification methods have a good agreement rates (Kappa = 0.7856), indicating the discriminant classification is of practical values. PMID- 7877198 TI - Sonographic diagnosis of acute hematogenous osteomyelitis in the early stage. AB - This article presents sonographic diagnosis of acute hematogenous osteomyelitis in early stage. 24 children with clinically suspected acute hematogenous osteomyelitis were detected to have subperiosteal abscesses by ultrasound during four to fourteen days after onset. The mean length and anteroposterior distance of the subperiosteal abscesses were 86.4 mm and 10.7 mm, respectively. Of 24 cases of subperiosteal abscesses, aspiration performed under ultrasound guidance revealed purulent fluid in all and 23 were verified surgically. The results obtained indicate that ultrasound can be used in diagnosis of acute hematogenous osteomyelitis in the early stage. The earliest case was diagnosed by ultrasound 4 days after onset. By use of ultrasound, differentiation diagnosis of acute hematogenous osteomyelitis from other diseases such as cellulitis, soft tissue abscess, acute septic arthritis and malignant bone tumors is also discussed. PMID- 7877200 TI - Importance of meticulous ultrasonographic investigation of the acardiac twin. PMID- 7877199 TI - An experimental study on membrane malignant phenotype of tumour cells and their reversion. AB - A human promyelocytic leukemic cell line (HL-60 cells) was induced to differentiate along the myeloid pathway in vitro by 1.25% dimethylsulfoxide (DMSO) as an inducer. The membrane fluidity, the quantity of ConA binding sites on the cell membrane surface, and the protein tyrosine kinase (Tyr-PK) activity existing in NP-40 membrane extract and cytoplasma extract were determined respectively. The activity of tumour-derived immunosuppressive factor (TDSF) secreted by HL-60 cells into culture supernatant was also determined. The results demonstrated that: (1) HL-60 cells were capable of undergoing differentiation onto the myeloid pathway in the presence of DMSO. The growth of DMSO-treated HL 60 cells became slow and synthesis rate of DNA decreased by about 50%. (2) Both membrane fluidity and the quantity of ConA binding sites on membrane were obviously lower after induced with DMSO than those before induction. (3) The Tyr PK activity in the NP-40 membrane extract increased during the period of induced differentiation. The phosphorylation level of endogenous protein in cytoplasma extract decreased with the process of induced differentiation. It may be reasoned that the phosphatase activity is much higher than the phosphorylase activity. (4) The secretive level of TDSF by HL-60 cells during the period of induced differentiation revealed no change. The preliminary results showed that the malignant phenotypes of tumour cells we used may undergo reversible changes with induced differentiation of tumour cells except the secretion of TDSF. PMID- 7877201 TI - Enhanced transvaginal sonographic depiction of caput succedaneum prior to labor. PMID- 7877202 TI - Benign cystitis in children mimicking rhabdomyosarcoma. AB - Seventeen (13 male, 4 female) patients, aged 13 months to 13 years, with benign cystitis had imaging findings that mimicked those of rhabdomyosarcoma. Our experience indicates that in the child with hematuria, dysuria, and frequency plus cystographic or sonographic demonstration of a bladder with reduced capacity and circumferential wall thickening or sonographic findings of isoechoic bladder wall thickening (focal, multifocal or circumferential distribution), intact mucosa, and bullous lesions should strongly suggest inflammation and not malignancy. When an inflammatory lesion is suspected, follow-up imaging should be performed in 2 weeks, which if normal will preclude biopsy. PMID- 7877203 TI - Optimizing transperineal sonographic imaging of the cervix: the hip elevation technique. AB - Although transperineal ultrasonography is a valuable technique for imaging the cervix in pregnancy, transperineal imaging can be compromised when bowel gas obscures the external portion of the cervix. To determine if a hip elevation technique could improve visualization of a partially obscured cervix, transperineal scanning was performed with the hips and buttocks elevated on a thick cushion in 23 patients with suboptimal routine transperineal views. The "hips up" maneuver was tolerated by all patients and improved cervical visualization in 19 of 23 cases. We conclude that the simple maneuver of elevating the patient's hips and buttocks on a thick cushion is a useful adjunctive technique to improve transperineal imaging of the cervix when routine transperineal views are compromised by adjacent bowel gas. PMID- 7877204 TI - Significance of orbital measurements in the fetus. AB - Orbital imaging is not performed routinely during obstetrical sonography, but the discovery of abnormal orbital diameters provides evidence of fetal dysgenesis. This study was designed to establish the validity of a previously developed orbital nomogram for a high-risk population and to determine whether proved cases of hypotelorism and hypertelorism fell outside the normal ranges. Inner and outer orbital measurements of 422 fetuses were obtained prospectively during routine obstetrical sonography in a high-risk patient population. Comparison of these measurements to the previously established nomogram demonstrated that the nomogram is still accurate with current equipment and in a population at high risk for anomalies. In addition, sonograms and autopsy and clinical data from six cases of hypotelorism, two of cyclopia, and three of hypertelorism were reviewed retrospectively. Both inner and outer orbital measurements fell clearly below two standard deviations of the mean in all six cases of hypotelorism. The three cases of hypertelorism had inner orbital measurements above the 95th percentile and outer orbital distances within normal limits but near the 95th percentile. All cases with abnormal orbital distances had associated intra- or extracranial abnormalities, including holoprosencephaly, encephalocele, cleft palate, cardiac anomalies, imperforate anus, diaphragmatic hernia, and digit anomalies. PMID- 7877205 TI - Duplex Doppler sonographic evaluation of splanchnic and renal effects of single agent and combined therapy with nadolol and isosorbide-5-mononitrate in cirrhotic patients. AB - Thirty-eight cirrhotic patients with esophageal varices were investigated by duplex Doppler sonography. In every patient, the portal blood flow mean velocity (cm/sec) and portal blood flow volume (ml/min) were measured. In addition, the pulsatility index [(maximum-minimum)/mean velocity] was measured in the superior mesenteric artery, in the hepatic arteries, in an intrasplenic artery, and in intrarenal arteries. These parameters were measured again 120 to 180 minutes after administration of nadolol (80 mg orally) in 22 patients, 90 minutes after administration of isosorbide-5-mononitrate (20 mg orally) in nine patients, and subsequently after administration of isosorbide 5-mononitrate to 10 of the 22 patients treated earlier with nadolol. Duplex Doppler sonographic parameters also were evaluated in seven patients 120 minutes after administration of a placebo. In five of the 22 patients treated acutely with nadolol, the same parameters were measured again after 60 minutes without any additional drug administration. No hemodynamic changes occurred in response to the placebo. Portal blood flow mean velocity and portal blood flow volume decreased after nadolol and isosorbide-5 mononitrate; mesenteric pulsatility index increased after both nadolol and isosorbide-5-mononitrate. After combined therapy, we observed a further reduction in portal blood flow mean velocity and portal blood flow volume and a significant increase in hepatic, splenic, and mesenteric pulsatility indices. The addition of isosorbide-5-mononitrate to nadolol caused a decrease in portal blood flow mean velocity of more than 17% in all patients. Nadolol caused a slight increase in renal pulsatility index, which was amplified by the addition of isosorbide-5 mononitrate, suggesting a decrease in renal blood flow. PMID- 7877206 TI - Doppler sonography of varicocele: long-term follow-up after venography and transcatheter sclerotherapy. AB - Sixty-eight patients with unilateral left-sided idiopathic varicocele who had not been treated previously were examined with Doppler sonography before and 1, 3, and 12 months after selective venography with balloon occlusion and transcatheter sclerotherapy of the internal spermatic vein. Varicocele and its persistence or recurrence was diagnosed by reflux only. Reflux was differentiated into stop-type and shunt-type by Doppler sonography. The resolution of varicocele was defined by absence of any reflux. The rate of resolution was greatest 3 months after sclerotherapy (49 patients, 72%). The diagnosis of persisting or recurring varicocele at this time does not seem to be justified, however, as in our study both further improvement and deterioration were observed up to 12 months after treatment. Twenty patients (29%) had a persisting or recurring varicocele 12 months after sclerotherapy. Reflux is the parameter of significance for diagnosing varicocele and its persistence or recurrence after therapy. Improvement of clinical aspects of varicocele (e.g., sperm count, sperm motility, and conception rates) depends on therapy of even subclinical varicoceles. Therefore, diagnosis and retreatment of persistent or recurrent varicoceles seems essential. The high sensitivity of Doppler sonography permits adequate assessment of the therapeutic result and evaluation of real rates of persistent or recurrent varicoceles after venography with balloon occlusion and transcatheter sclerotherapy. PMID- 7877207 TI - Duplex ultrasonography: a noninvasive technique in monitoring of Le Veen shunt. AB - Monitoring of peritoneovenous Le Veen shunt by duplex ultrasonography was first performed in 1993 in 10 patients. The duplex signal was picked up selectively in the venous tube and the peak velocity was measured at forced inspiration. Thirty two examinations were performed. Of these, 13 had follow-up examinations by other modalities (radionuclide imaging, shuntography, or surgical exploration), all of which confirmed the findings of duplex ultrasonography. Shuntography was avoided in all instances with a patent shunt. Duplex ultrasonography allows noninvasive assessment of Le Veen shunt patency and appears reliable for determining the need for invasive diagnostic modalities or surgical shunt correction. PMID- 7877208 TI - Fetal intraluminal gastric masses after second trimester amniocentesis. AB - Eight instances of homogeneous, well-defined echoes within the fetal stomach were identified on routine second trimester detailed scan over a 7 month period, a prevalence of 1 in 287 or 0.35%. This finding was significantly more frequent in women who had cytogenetic amniocentesis than in those who had not had the procedure (4 in 266 [1.5%] versus 4 in 2031 [0.2%], respectively; P < 0.01). Indirect signs of intra-amniotic bleeding, such as particles in the amniotic fluid, chorioamniotic separation, or hyperechogenic bowel, were present in four cases. The association between echogenic material within the fetal stomach and cytogenetic material within the fetal stomach and cytogenetic amniocentesis is discussed. PMID- 7877209 TI - Prenatal sonographic detection of cardiac aneurysms and diverticula. AB - We describe three cases of isolated ventricular aneurysm or diverticulum detected antenatally, with subsequent prenatal serial study and postnatal follow-up. Two pregnancies with in utero left ventricular aneurysm, both involving the apex, were referred for fetal atrial arrhythmias at 28 and 25 weeks of gestation, respectively. The aneurysms had a saccular appearance and were thin-walled and hypokinetic. In a third pregnancy, referred for an abnormal four-chamber view, the fetus was found to have a right ventricular aneurysm or diverticulum protruding beneath the tricuspid valve annulus. All three continued to term and at no time demonstrated cardiovascular compromise. PMID- 7877210 TI - Corpus luteum blood flow in normal and abnormal early pregnancy: evaluation with transvaginal color and pulsed Doppler sonography. AB - One hundred and thirteen (66.5%) women in this study had a normal intrauterine pregnancy with ages ranging 6 to 12 weeks of gestation. Fifty-seven (33.5%) patients were admitted to the hospital owing to clinically suspected abnormal early pregnancy. Dilatation and curettage were done on all women and tissue sample sent to the pathologist for a final diagnostic. Diagnosis of ectopic pregnancy was made on laparoscopy. Both ovaries were examined carefully by color Doppler in sonography in all patients. Color flow was used as a guide for pulsed Doppler exploration. Corpus luteum blood flow was defined as random, usually semilunar in appearance, dispersed vessels with very low impedance to blood flow. The resistive index and pulsatility index were calculated. Overall detection rate of corpus luteum blood flow in normal pregnancies was higher for the left ovary (62.6%) than for the right ovary (37.4%) (P < 0.01). The mean resistive and pulsatility indices from corpus luteum blood flow were not influenced by gestational age in normal pregnancy. The overall mean value for for resistive index was 0.452 +/- 0.04 and for pulsatility index 0.636 +/- 0.09. The overall detection rate of corpus luteum in abnormal pregnancies also was higher for the left ovary (56.7%) than for the right ovary (43.4%) (P < 0.01). The mean resistive indices from corpus luteum blood flow in patients with missed abortion was higher than in women with normal pregnancy (P < 0.01). Both resistive and pulsatility indices were higher in patients with incomplete or threatened abortion in comparison with normal pregnancy (P < 0.01). No statistically significant difference was seen in the case of anembryonic, molar, or ectopic pregnancy. PMID- 7877211 TI - Fetal biometry of skeletal dysplasias: a multicentric study. AB - Twenty-three diagnostic centers worldwide contributed 127 cases of 17 skeletal dysplasias. Discriminant analysis showed that the femur length was the best biometric parameter to distinguish among the five most common disorders in this series (thanatophoric dysplasia, osteogenesis imperfecta type II, achondrogenesis, achondroplasia and hypochondroplasia). Fifty-four percent of fetuses with femur length below 30% of the mean for gestational age had achondrogenesis. Seventy-eight percent of measurements between 40 and 60% of the mean for gestational age represented either thanatophoric dysplasia or osteogenesis imperfecta type II. Fetuses who had over 80% of the mean for gestational age had predominantly hypochondroplasia, achondroplasia, and osteogenesis imperfecta type III. PMID- 7877212 TI - Endometrial thickness in postmenopausal women. PMID- 7877213 TI - Ultrasonographic diagnosis of perineal hernia. PMID- 7877214 TI - Fetal urinoma: a case report and review of its clinical significance. PMID- 7877216 TI - Prenatal sonographic detection of single and double umbilical artery in the same fetus. PMID- 7877215 TI - Prenatal diagnosis and management of umbilical vein varix of the intra-amniotic portion of the umbilical vein. PMID- 7877217 TI - Detection of complications of cystic fibrosis. PMID- 7877218 TI - The role of cinefluoroscopy and intravascular ultrasonography in evaluating the deployment of experimental endovascular prostheses. AB - PURPOSE: This study compares the utility of cineangiography and real-time intravascular ultrasonography (IVUS) in achieving successful deployment of endovascular prostheses. METHODS: Five types of 5 cm long, 8 mm internal diameter polyester vascular grafts were secured in the infrarenal aorta of mongrel dogs by 18 mm long Palmaz balloon expandable vascular stents sutured to each end of the prostheses. The endovascular prostheses were delivered by crimping the stents at the ends of the grafts onto a 10 mm outside diameter, 8 cm long polyethylene balloon-dilation catheter. Real-time IVUS of the procedure was provided by a 0.035-inch, 20 MHz imaging element passed through the guide wire lumen in the balloon catheter. Two prostheses of each type were implanted, with one removed at 30 days and the other at 60 days for analysis. RESULTS: At implantation, both angiography and IVUS provided information regarding the choice of site for placement of the device and sizing of the aortic lumen. Real-time IVUS enhanced the information obtained by cineangiography by displaying tomographic views of the vessel anatomy, enabling determination of cross-sectional areas, assessing full stent expansion, and providing information regarding surface topography along the length of the prostheses. Several critical observations were apparent only on IVUS, including incomplete initial stent expansion during two procedures evidenced by pulsation of the aortic wall independent of the stent and movement of unstented segments of thin-walled grafts. Some of these observations led to further interventions at the time of deployment. At death, a comparison of cineangiography, IVUS, and ultrafast computed tomography outlined lumenal continuity and areas of irregularity, thrombus, or narrowing, with IVUS being more sensitive than cineangiography or computed tomography for determining most parameters. CONCLUSIONS: We conclude that IVUS is a promising alternative method for precise placement of intravascular grafts. PMID- 7877219 TI - Dorsalis pedis arterial bypass: durable limb salvage for foot ischemia in patients with diabetes mellitus. AB - PURPOSE: Although the technical feasibility of pedal artery bypass for limb salvage is now well established, questions remain about its most appropriate use and its long-term durability. METHODS: We reviewed our experience over an 8-year period in 367 consecutive patients undergoing 384 vein bypass grafts to the dorsalis pedis for limb salvage. RESULTS: Ninety-five percent of the patients had diabetes mellitus. Infection complicated ischemia at initial presentation in 55.2% of patients. The preoperative arteriogram demonstrated a patent dorsalis pedis in 362 extremities (92.8%). Four hundred two patients underwent exploration for bypass, including 29 patients without demonstrated arteries on the arteriogram but audible pedal Doppler signals. Successful bypasses were carried out in 357 of 362 cases, where preoperative arteriography demonstrated a patent dorsalis pedis artery (98.6%), 16 of 28 cases explored on the basis of a Doppler signal alone (57%), and 11 of 12 patients where angiographic status was unknown. All procedures were performed with vein: in situ 38.5%, reversed 29%, nonreversed 18%, arm vein 7%, and composite vein 8%. Inflow was taken from the common femoral artery in 34%, superficial femoral or popliteal arteries in 60%, a previously placed graft in 5%, and a tibial artery in 1%. There were seven perioperative deaths (1.8%) and 21 myocardial infarctions (5.4%). Twenty-nine grafts failed within 30 days (7.5%), but 19 were successfully revised. Eight of the 10 failed grafts resulted in major amputation (80%). Over the remaining study period, there were 39 additional graft failures, of which 17 were successfully revised, and 17 additional major amputations. Actuarial primary and secondary patency and limb salvage rates were 68%, 82%, and 87%, respectively, at 5 years' followup. The actuarial patients survival rate was 57% at 5 years. Patency rates were similar for in situ and translocated saphenous vein grafts. CONCLUSIONS: Dorsalis pedis arterial bypass is an effective limb salvage procedure with long-term durability comparable to distal vein grafts placed into more proximal arteries. PMID- 7877220 TI - Aneurysms of the descending thoracic aorta: three hundred sixty-six consecutive cases resected without paraplegia. AB - PURPOSE: The aim of this study was to present a 20-year experience with a single method of passive distal perfusion during descending thoracic aortic aneurysm resection. METHODS: Aortic repair with a Dacron graft interposition was performed for 366 consecutive aneurysms located between the left subclavian artery and the crux of the diaphragm. The extent of aorta resected in 335 patients (91.5%) represented one third or less of the aortic length. A 9 mm Gott shunt was cannulated proximally into the ascending aorta (235 cases), the aortic arch (60 cases), the descending aorta (68 cases), or the left ventricle (3 cases) and inserted distally into the descending aorta (232 cases), the femoral artery (127 cases), or the abdominal aorta (7 cases). Shunt flows were recorded in 91 cases and varied from 1100 ml to 4900 ml/min, (mean 2526 ml/min). Distal pressure during shunting was measured in 62 patients. It varied from 15 to 120 mm Hg (mean 64.5 mm Hg). The aortic cross-clamp time varied from 8 to 124 minutes (mean 30 minutes). RESULTS: The hospital death rate was 12% overall and 9.9% (35/351) if ruptured aneurysms are excluded. Among 359 operating room survivors, neither immediate nor delayed ischemic spinal cord deficit occurred. Transient renal dysfunction occurred in nine patients (2.4%) and kidney failure in one (0.2%). Five deaths (1.3%) were shunt related. CONCLUSION: Distal perfusion with the 9 mm Gott shunt has proven to be an effective method to preserve spinal cord function. The limited extent of aorta resected and the brief aortic cross-clamp time may also be interactive factors of protection. PMID- 7877221 TI - Hypothermia during elective abdominal aortic aneurysm repair: the high price of avoidable morbidity. AB - PURPOSE: Adverse outcomes apparently associated with hypothermia led us to examine patients undergoing elective abdominal aortic aneurysm (AAA) repairs to test the hypothesis that hypothermia (temperature less than 34.5 degrees C) is associated with increased morbidity and excess mortality rates. METHODS: Two hundred sixty-two elective AAA repairs were retrospectively reviewed for preoperative and intraoperative risk factors. Core temperature, age, Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III scores (raw and temperature-adjusted), fluid resuscitation, and perioperative organ dysfunction were recorded prospectively. Outcome measures included lengths of stay in the intensive care unit and in the hospital, and hospital mortality rates. RESULTS: Except for a higher risk of hypothermia in women (p < 0.05), by univariate analysis, preoperative risk factors were similar in patients in the hypothermic and normothermic groups. After operation, patients with hypothermia had significantly greater APACHE scores (p < 0.0001), and patients in the hypothermic nonsurvivor group took significantly longer to rewarm (p < 0.05), suggesting marked hypoperfusion. Patients with hypothermia had significantly greater fluid (p < 0.05), transfusion (p < 0.01), vasopressor (p < 0.05), and inotrope (p < 0.05) requirements, resulting in significantly higher incidences of organ dysfunction (53.0% vs 28.7%, p < 0.01) and death (12.1% vs 1.5%, p < 0.01) and markedly prolonged lengths of stay in the unit (9.2 +/- 2.0 vs 5.3 +/- 0.6, p < 0.05) and in the hospital (24.3 +/- 2.9 vs 15.0 +/- 0.08, p < 0.01). By multivariate analysis, female gender (p = 0.004) was the only predictor of intraoperative hypothermia, whereas initial hypothermia was significantly predictive of both prolonged hypothermia and development of organ failure (p < 0.05). Organ failure (p < 0.05) and acute myocardial infarction (p < 0.01) were independent predictors of death. CONCLUSIONS: After AAA repair, patients with hypothermia have multiple physiologic derangements associated with adverse outcomes. Although multiple etiologic factors are interacting, body temperature is one variable that should be controlled during aortic surgery. PMID- 7877222 TI - The use of spliced vein bypasses for infrainguinal arterial reconstruction. AB - PURPOSE: The use of autogenous vein, whether in situ or excised, for arterial bypass procedures is well accepted. However, this usually requires the presence of a length of good-quality vein of adequate diameter. In patients lacking sufficient length of vein, two or more pieces of vein may be spliced together to complete the reconstruction. The effect of vein splicing on vein bypass patency is not well studied. METHODS: Over a 14-year period, 1956 lower extremity revascularizations were performed with a single autogenous vein, 1806 in situ and 150 excised veins. During the same time, 184 bypasses required splicing vein segments together, of which 111 were in situ bypass procedures, which required splicing of one or more pieces of excised vein to complete the reconstruction (partial in situ bypass). Seventy-three bypasses were completed with multiple pieces of spliced excised vein. The source for the excised, spliced vein segments was the distal ipsilateral greater saphenous vein (GSV) in 40%, accessory ipsilateral GSV in 8%, contralateral GSV in 13%, lesser saphenous vein in 28%, and arm vein in 11%. RESULTS: The 1- and 4-year primary patency rates for the entire spliced vein group were 72% and 45%, with secondary patency rates of 79% and 61%. The 1- and 4-year secondary patency rates of partial in situ bypasses were 80% and 70%, compared with 91% and 83% for in situ bypasses completed without a spliced segment (p < 0.0001). The 1- and 4-year secondary patency rates were 78% and 67% in the spliced excised vein group and 85% and 75% in the single excised vein group (p = not significant). The 4-year limb salvage rates were as follows: in situ (96%), partial in situ (85%), single excised vein (95%), and spliced excised vein (90%). CONCLUSIONS: We conclude that the use of excised vein segments to complete partial in situ bypasses may be associated with a decrement of bypass patency. Use of spliced excised vein segments of good quality for arterial bypass can produce acceptable patency rates. Such spliced autogenous conduits are clearly preferable to prosthetic bypasses for infrageniculate arterial reconstructions. Meticulous technique is a prerequisite for the successful performance of vein-to-vein anastomoses. PMID- 7877223 TI - Endothelial cell seeding fails to attenuate intimal thickening in balloon-injured rabbit arteries. AB - BACKGROUND: Restenosis of arteries or bypass grafts after vascular reconstruction is a common clinical entity that significantly limits long-term patency. This process, termed intimal hyperplasia (IH), is characterized by smooth muscle cell proliferation in the intima and subsequent accumulation of intercellular matrix. This study was designed to test the hypothesis that endothelial cell (EC) seeding of acutely injured arteries accelerates reendothelialization of the flow surface and limits the development of IH. METHODS: ECs were harvested from jugular veins of New Zealand white rabbits (n = 13) and were amplified in tissue culture. Each animal subsequently underwent bilateral balloon catheter injury of the iliofemoral arteries; one side was immediately seeded with cultured autologous ECs at supraconfluent density, whereas the contralateral vessel served as a nonseeded control. Animals were killed 33 +/- 5 days after balloon injury. Intimal thickening was quantitated on histologic sections of vessels (three sections per vessel, total of 60 sections) and percent endothelialization was assessed by SEM; measurements were obtained by use of computer-aided morphometry performed by a blinded observer. Data were analyzed by use of a paired t test for comparison between seeded and control vessels. RESULTS: Seeded vessels exhibited a greater degree of reendothelialization (93.9% +/- 7.6% of the surface) than their unseeded counterparts (65.1% +/- 22.5%, p < 0.01). Intimal cross-sectional area and the ratio of intimal area to medial area were not significantly different between seeded and control vessels (intima: 0.32 +/- 0.19 vs 0.37 +/- 0.11 mm2, p = 0.28; intimal area to medial area ratio: 0.84 +/- 0.35 vs 1.02 +/- 0.2, p = 0.24). CONCLUSIONS: We conclude that seeding with autologous venous ECs accelerated restoration of the endothelial monolayer but failed to attenuate IH in balloon-injured rabbit arteries. Further studies are necessary to determine the functional properties of seeded endothelium and to examine the effect of EC seeding on intimal thickening in other clinically relevant models. PMID- 7877224 TI - Racial differences in the incidence of femoral bypass and abdominal aortic aneurysmectomy in Massachusetts: relationship to cardiovascular risk factors. AB - PURPOSE: Atherosclerotic disease appears to be more severe in black patients than in white patients, but abdominal aortic aneurysms, which have traditionally been believed to have an atherosclerotic cause, are reported to be less common in black patients than in white patients. Our goals were to compare and contrast factors associated with the development of abdominal aortic aneurysms and clinically significant atherosclerotic occlusive disease (1) to determine whether these diseases share a common cause and (2) to explore their association with race. METHODS: Dual case-control studies were conducted with multivariate analysis to compare cases (patients undergoing aneurysmectomy or patients undergoing femoral bypass) with a comparison group consisting of patients who had undergone appendectomy. Two data sources were used: (1) hospital discharge data for Massachusetts from 1984 through 1988 and (2) medical records at University Hospital of Boston and Boston City Hospital. For both the Massachusetts database and the hospital chart review, records were obtained for all patients discharged between January 1984 and December 1988 with an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) procedure code for abdominal aortic aneurysm resection (38.44) or aneurysmorrhaphy (38.34) or with a procedure code for femoral artery bypass/reconstruction (39.29). To conduct a nested case-control study, records were also obtained for a control group consisting of patients between the ages of 50 and 84 years who had undergone appendectomy during the same 5-year period. RESULTS: Black patients had higher rates of femoral bypass than did white patients after adjustment for age and sex (odds ratio = 1.97; 95% confidence interval: 1.49, 2.61; p < 0.0001). However, femoral bypass was also associated with hypertension, diabetes, and low household income. After adjusting for these additional factors in the statewide data set, the black/white odds ratio for femoral bypass was only 1.44 (95% confidence interval: 1.08, 1.92). The parallel case-control study at University Hospital and Boston City Hospital, which provided information about smoking status and more accurate ascertainment of coexisting hypertension and diabetes, indicated that there was no racial difference in rates of femoral bypass after correcting for these additional risk factors (odds ratio = 0.94; 95% confidence interval: 0.40, 2.22; p = 0.90). In contrast, abdominal aortic aneurysmectomy occurred predominantly in white men. Aneurysmectomy was also associated with smoking and hypertension, but aneurysmectomy was not significantly associated with diabetes mellitus or family income. The black/white odds ratio for aneurysm was 0.29; (95% confidence interval: 0.07, 1.23; p = 0.09 after adjustment for other variables). CONCLUSIONS: Hypertension, smoking, and male sex are risk factors for the development of femoral atherosclerosis and abdominal aortic aneurysm formation. However, abdominal aortic aneurysms occur predominantly in white men and do not appear to be associated with diabetes mellitus or income. In contrast, the higher rate of femoral artery bypass in black patients is probably the result of greater prevalence among black patients of hypertension, diabetes, smoking, and perhaps by other ill-defined factors associated with socioeconomic status. PMID- 7877225 TI - Marfan syndrome: the variability and outcome of operative management. AB - PURPOSE: This study reviews the contemporary surgical outcome of 69 patients with Marfan syndrome who underwent one or more aortic operations between July 18, 1989, and April 14, 1994. METHODS: During this 5-year period, 79 operations were performed including composite valve graft replacement (n = 28) and graft replacement of the thoracoabdominal aorta (n = 29). Fifty-seven additional operations had been performed before referral, for a total of 136 aortic operations in this group. Forty-two patients (60.9%) required multiple operations; 16 patients (23.2%) underwent three or more procedures. RESULTS: Follow-up was complete on all patients. The 30-day and long-term survival rates were 98.7% and 96.2%, respectively. Distal aortic replacement resulted in paraparesis in only one (2.6%) of 38 patients; no patient had development of paraplegia. No patient had a stroke after the use of profound hypothermic circulatory arrest. CONCLUSION: Aortic surgery prolongs survival in patients with Marfan syndrome and currently has low associated morbidity and mortality rates. Treatment often requires multiple staged operations. The variety and multiplicity of aortic manifestations in these patients demonstrate the necessity for lifelong cardiovascular surveillance to detect new or recurrent disease. PMID- 7877226 TI - The effect of peripheral vascular disease on in-hospital mortality rates with coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group. AB - PURPOSE: The purpose of this study was to examine the effect of peripheral vascular disease (PVD) on in-hospital mortality rates after coronary artery bypass grafting (CABG). METHODS: We performed a regional cohort study of 3003 patients undergoing CABG between 1987 and 1989 at five tertiary care centers in Maine, New Hampshire, and Vermont. Data reflecting patient characteristics, severity of heart disease, comorbidity, and in-hospital mortality rates were collected prospectively; the presence of clinical and subclinical indicators of PVD was determined retrospectively. RESULTS: Observed in-hospital mortality rates with CABG were 2.4-fold higher in the 796 patients with indicators of PVD (7.7%) than in the 2207 patients without PVD (3.2%) (crude odds ratio [OR] 2.42 [95% confidence interval (CI) 1.73-3.37]). After adjusting for their higher comorbidity scores, more advanced heart disease, and age, patients with PVD remained 73% more likely to die in hospital after CABG (adjusted OR 1.73 [CI 1.19 2.51]). The excess risk of in-hospital death associated with PVD was attributable largely to lower extremity occlusive disease (adjusted OR 2.03 [CI 1.34-3.07]). Subclinical lower extremity occlusive disease (asymptomatic absence of pedal pulses) had the same effect as clinically overt disease. Cerebrovascular disease had a small and statistically nonsignificant effect on CABG-related deaths (adjusted OR 1.13 [CI 0.73-1.74]). Excess mortality rates in patients with PVD were primarily due to increased risk of death from heart failure and dysrhythmias, but not to cerebrovascular accidents or peripheral arterial complications. CONCLUSIONS: The presence of lower extremity arterial occlusive disease is an important, independent predictor of in-hospital mortality rates for patients undergoing CABG. Controlled studies of the long-term effects of CABG in patients with PVD are needed to determine the optimal role of myocardial revascularization in this population. PMID- 7877227 TI - The value and limitations of L-arginine infusion on glomerular and tubular function in the ischemic/reperfused kidney. AB - PURPOSE: The nitric oxide precursor, L-arginine, has been shown to have a salutary effect on ischemia and reperfusion injury in skeletal muscle, skin, and intestines. Because L-arginine also increases renal blood flow, glomerular filtration, and urine flow in experimental animals with normal renal function, we postulated that L-arginine may also improve renal function after renal ischemic injury. METHODS: Eighteen adult New Zealand white rabbits weighing 3 to 3.5 kg were subjected to bilateral normothermic renal ischemia by clamping both renal pedicles for 1 hour followed by 2 hours of reperfusion. The animals were randomized into three groups: group I (control, n = 6) received no additional treatment; group II (pretreatment, n = 6) received systemic intravenous L arginine at 150 mg/kg over 20 minutes before induction of ischemia; group III (posttreatment, n = 6) received systemic intravenous L-arginine at 150 mg/kg over 20 minutes from the onset of reperfusion. Urine flow, creatinine clearance (CCR), fractional excretion of sodium (FENa), and renal failure index (RFI) were calculated before ischemia and 2 hours after reperfusion, by use of standard formulas. The changes of the various renal parameters were compared among the three groups. RESULTS: Bilateral normothermic renal ischemia for 1 hour produced a significant deterioration of glomerular filtration as evidenced by a CCR decrease from 11.1 +/- 1.8 to 2.49 +/- 0.9 ml/min (p < 0.01), FENa increase from 2.9% +/- 1.0% to 20.8% +/- 1.5% (p < 0.01) and RFI increase from 4.0 +/- 1.3 to 28.8 +/- 2.6 (p < 0.01). Pretreatment with L-arginine (group II) minimized the deleterious effects caused by ischemia on glomerular filtration (CCR of 2.49 +/- 0.9 ml/min in group I vs 4.95 +/- 2.5 ml/min in group II, p < 0.05) and tubular function (FENa of 20.8% +/- 1.5% in group I vs 13.0% +/- 5.6% in group II and RFI of 28.8 +/- 2.6 in group I vs 18.6 +/- 8.0 in group II, p < 0.05). Infusion of L arginine at the onset of reperfusion (group III) produced a significant diuretic effect (urine flow from 32.6 +/- 13.4 ml/hr in group I to 63.3 +/- 18.8 ml/hr in group III, p < 0.05) and also minimized glomerular damage (CCR from 2.49 +/- 0.9 ml/min in group I to 4.80 +/- 1.2 ml/min in group III, p < 0.05); however, no beneficial effect was observed on tubular function. CONCLUSION: Induction of nitric oxide production by systemic L-arginine infusion can best preserve glomerular and tubular function in the ischemic/reperfused kidney when given before the ischemic insult. PMID- 7877228 TI - The anastomosis angle does change the flow fields at vascular end-to-side anastomoses in vivo. AB - PURPOSE: The purpose of this article was to study the influence of the anastomosis angle on the flow fields at end-to-side anastomoses in vivo. METHODS: Polyurethane grafts of similar internal diameter to that of the abdominal aorta (8 mm) were implanted from the suprarenal to the infrarenal level in 10 pigs. Three angles of standardized distal end-to-side anastomoses (90 degrees, 45 degrees, and 15 degrees) were studied. The anatomic position of the anastomoses was constant, the proximal outflow segment was occluded, and the flow rate through the graft was controlled. Flow visualization was accomplished by a color flow Doppler ultrasound system. RESULTS: The angulation was reproduced within 10%. Gross hemodynamic parameters were stable, and the similarity parameters were typical for peripheral bypasses (mean Reynold's number is 424 and Womersley's parameter is 5.9). The flow fields were clearly dependent on the anastomosis angle. A zone of recirculation (approximately 5% of the flow area), extending from the toe to one diameter downstream, was found in the 45-degree and 90-degree anastomoses. No flow disturbances were detected at the toe and one diameter downstream with an anastomosis angle of 15 degrees. At the heel different recirculating flow patterns were found in the different anastomoses. CONCLUSION: The anastomosis angle does change the flow fields at vascular end-to-side anastomoses in vivo. PMID- 7877229 TI - Venous duplex imaging follow-up of acute symptomatic deep vein thrombosis of the leg. AB - PURPOSE: The purpose of this study was to evaluate the rate of resolution of deep vein thrombosis (DVT) in the leg, by means of duplex imaging, in patients with symptoms during a 6-month period after initial diagnosis. METHODS: Seventy-three limbs in 69 patients with acute DVT diagnosed by duplex imaging received conventional heparin and warfarin treatment and underwent subsequent duplex studies 1, 4, 12, and 24 weeks after the initial diagnosis. The objectives of the study were to document (1) the rate or complete resolution of DVT, (2) the proportion of unstable, floating thrombi, and (3) the development of chronic damage as a result of vessel wall scarring. RESULTS: The rate of normalization of DVT 6 months after diagnosis was 78% in the common femoral vein, 70% in the superficial femoral vein, 75% in the popliteal vein, and 70% in the calf veins examined at the scheduled intervals. Twenty-six percent of thrombi were considered unstable on the baseline examination. The average number of days necessary for these thrombi to become stable was 10.7 days. Damage to the vessel wall or valves was documented in 44% of the patients. CONCLUSIONS: Rates of resolution of DVT were similar for the different veins of the leg studied. There was a high proportion of unstable thrombi, which present a high potential risk of embolization. Serial duplex scanning after DVT renders important information with regard to thrombus resolution, propagation, and attachment to the vein wall. PMID- 7877230 TI - Heparinoids with low anticoagulant potency attenuate postischemic endothelial cell dysfunction. AB - PURPOSE: Although standard heparin has been demonstrated to reduce endothelial cell dysfunction in acute ischemia-reperfusion injury, its mechanism of action remains unknown. We hypothesized that heparin's salutary endothelial effects are independent of its conventional anticoagulant activity and are not caused by nonspecific polyanion effects. METHODS: Isolated rat hindlimbs were perfused at constant pressure with an albumin-enriched crystalloid buffer. After 60 minutes of normothermic ischemia, endothelial function was assessed by measurement of endothelial-dependent vasodilation by log increment infusion of acetylcholine. Endothelial-independent vasodilation was measured by exposure to nitroprusside. Some groups were pretreated with heparinoids possessing minimal or intermediate anticoagulant activity. RESULTS: Treatment with heparinoids with low anticoagulant activity significantly increased endothelial-dependent vasodilation when compared with the nontreated ischemic group and were statistically indistinguishable from the nonischemic control. Treatment with dextran sulfate, a randomly sulfated polymer with size and charge characteristics similar to heparin, did not change postischemic vasodilation. Endothelial-independent vasodilation was largely unaffected by ischemia-reperfusion or drug treatment. CONCLUSIONS: A heparinoid with negligible antithrombin-binding activity (Astenose) attenuated postischemic endothelial dysfunction, suggesting that its mechanism of action was independent of anticoagulant activity. Failure of dextran sulfate to be protective implied that the effect was not caused by nonspecific polyanion action. PMID- 7877231 TI - Platelet count and the outcome of operation for ruptured abdominal aortic aneurysm. AB - PURPOSE: The purpose of this study was to determine the relationship between admission and postoperative platelet count (PC) and mortality and morbidity rates after emergency surgery for ruptured abdominal aortic aneurysm (AAA). METHODS: We performed a case record review of 65 consecutive patients admitted with ruptured AAA. RESULTS: Five patients did not undergo operation because of poor clinical condition, 12 patients died at operation, 13 patients died after operation, and 35 patients survived (operative mortality rate of 58%). Fifteen patients had an admission PC of less than 150 x 10(9)/L, of whom 14 (93%) died; 27 patients had an admission PC of 150 to 250 x 10(9)/L, of whom 8 (30%) died; and 18 patients had an admission PC of greater than 250 x 10(9)/L of whom 3 (17%) died. At the end of operation 29 patients had a PC of less than 100 x 10(9)/L, of whom 13 (45%) died, 20 (69%) had development of multiorgan failure (MOF), and 6 (21%) required relaparotomy for bleeding complications. By contrast, all 19 patients having a PC of 100 x 10(9)/L or greater at the end of the operation survived, three (16%) had development of MOF, and none required further surgery for bleeding. There was a significant inverse correlation between PC at the end of the operation and the number of postoperative days spent on a ventilator, in the intensive therapy unit, and in hospital. After operation, 15 patients had development of thrombocytosis (PC > 400 x 10(9)/L), of whom 10 had development of deep venous thrombosis and 8 had development of pulmonary embolism. There were no deep venous thromboses or pulmonary embolisms in patients who did not have development of a postoperative thrombocytosis. CONCLUSIONS: There is a direct correlation between PC on admission to the hospital and death after emergency repair of ruptured AAA. Thrombocytopenia at the end of the operation is associated with a high risk of morbidity from continuing hemorrhage or MOF. The development of postoperative thrombocytosis is associated with a high risk of thromboembolic complications. PC provides a simple marker of outcome in patients diagnosed with and undergoing operation for ruptured AAA. PMID- 7877232 TI - Inhibition of platelet deposition by combined hirulog and aspirin in a rat carotid endarterectomy model. AB - PURPOSE: Hirulog, a thrombin-specific inhibitor, has shown efficacy in reducing arterial thrombosis in patients treated with aspirin who require angioplasty or have unstable angina. In this study, the effect of hirulog on reducing deposition of indium 111-labeled platelets was assessed in a surgical model of aspirin treated rats undergoing carotid endarterectomy. METHODS: Animals were randomly assigned to one of five groups: control (no aspirin or hirulog); aspirin alone (10 mg/kg); aspirin plus low-dose hirulog (0.2 mg/kg bolus followed by 0.5 mg/kg/hr); aspirin plus medium-dose hirulog (0.4 mg/kg bolus followed by 1.0 mg/kg/hr); or aspirin plus high-dose hirulog (0.6 mg/kg bolus followed by 1.5 mg/kg/hr). Hirulog was infused before surgery and continued until termination of the experiment 30 minutes after endarterectomy. RESULTS: Platelet deposition in rats receiving aspirin alone was reduced by 19% +/- 23% SE (p = 0.26) compared with controls. Deposition in aspirin-treated groups receiving low-, medium-, and high-dose hirulog decreased in a dose-dependent manner by 37% +/- 20% (p = 0.048), 44% +/- 19% (p = 0.061), and 56% +/- 13% (p = 0.022), respectively. As the dose of hirulog was increased, the plasma hirulog levels and activated partial thromboplastin time ratios (final:initial) also increased in a dose dependent manner. The mean plasma hirulog levels ranged from 0.74 +/- 0.08 micrograms/ml in the low-dose hirulog group to 2.55 +/- 0.08 micrograms/ml in the high-dose hirulog group, and the corresponding activated partial thromboplastin time ratios were 1.5 +/- 0.12 (p = 0.001) and 3.3 +/- 0.63 (p = 0.001). Bleeding was easily controlled by local hemostatic measures for all experimental groups. CONCLUSION: Hirulog causes significant decrease in 111In-labeled platelet deposition in aspirin-treated rats subjected to microsurgical endarterectomy at doses that allow surgical hemostasis to be easily established. PMID- 7877233 TI - Nitroglycerin decreases medial smooth muscle cell proliferation after arterial balloon injury. AB - PURPOSE: Nitroglycerin and its effector molecules nitric oxide and cyclic guanosine monophosphate decrease smooth muscle cell proliferation in vitro. We examined the in vivo effect of nitroglycerin on intimal hyperplasia. METHODS: We treated rats after carotid artery balloon injury with nitroglycerin delivered paraarterially with a miniosmotic pump for 1 week. RESULTS: High nitroglycerin serum levels were achieved, and the level of cyclic guanosine monophosphate in the carotid artery wall was significantly increased (1.48 +/- 0.37 vs 0.86 +/- 0.39 pmol/mg protein; p < 0.05) in the nitroglycerin-treated group. Cellular proliferation in the arterial wall was assessed by incorporation of 5-bromo-2' deoxyuridine 6 days after the injury and was lower in the nitroglycerin-treated group (15.2 +/- 3.4 vs 36.3 +/- 5.5 positive cells/section; p < 0.005). This was due to a decrease in the number of proliferating cells in the media (6.3 +/- 1.2 vs 21.8 +/- 4.5; p < 0.005), whereas in the budding neointima, the difference in the number of proliferating cells was not significant. Neointimal lesions 21 days after the injury did not differ in cross-sectional intimal area, in intimal/medial area ratio, and in cell density. CONCLUSION: Nitroglycerin decreased medial cellular proliferation after balloon injury and had no significant effect on intimal proliferation. The size of the neointimal lesion was not affected by nitroglycerin therapy. PMID- 7877234 TI - Aneurysm of the superior mediastinal veins. AB - A case of true venous aneurysm with saccular dilation of the proximal half of the superior vena cava, the right innominate vein, and the distal two thirds of the left innominate vein in an 18-year-old white woman is presented. At surgery part of the aneurysmal wall was resected, and subsequently the mediastinal venous system was reconstructed with use of the rest of the aneurysmal wall. The postoperative course was uneventful. Operative treatment of mediastinal venous aneurysms is indicated to prevent possible major complications. We strongly suggest performance of this surgery only by means of a heart-lung machine. PMID- 7877235 TI - Iliac compression syndrome treated with stent placement. AB - Iliac compression syndrome is usually diagnosed during the third and fourth decades of life when the patient has iliofemoral deep vein thrombosis. Catheter directed thrombolytic therapy is an accepted method of treatment for iliofemoral deep vein thrombosis, which has been reported to afford greater success with clot dissolution than with system therapy. Although this method is not new, this is the first case, to our knowledge, reporting successful treatment of computerized tomographically demonstrated iliac compression syndrome with stent placement after lysis and insufficient response to balloon angioplasty. PMID- 7877236 TI - Arterial dissections associated with pregnancy. AB - Two cases of spontaneous arterial dissection occurring in young, multiparous women shortly after delivery of uncomplicated pregnancies are described. Histologic analysis of arterial tissue samples obtained in both cases at points near and remote from the dissection sites shows evidence of significant arterial degeneration and loss of integrity, with changes similar to those observed in pregnant women, women using oral contraceptives, and animals given female sex hormones. The types of arterial lesions associated with pregnancy and their sites of predilection and the etiologic roles of the hemodynamic stresses of pregnancy and hormones are discussed. PMID- 7877237 TI - Atherosclerotic aneurysm of the intrathoracic subclavian artery: a case report and review of the literature. AB - True aneurysm of the subclavian artery is extremely rare. Excluding the more common aneurysms of an aberrant right subclavian artery, those associated with thoracic outlet syndrome, and posttraumatic "aneurysms," atherosclerosis is the most common cause. Syphilis, tuberculosis, and cystic medial necrosis are less often the cause. These aneurysms can rupture, thrombose, embolize, or cause symptoms by local compression. Surgical treatment is generally indicated, and has evolved from ligation procedures to extirpation or endoaneurysmorrhaphy to the present practice of resection with revascularization. A case of a surgically treated, asymptomatic, atherosclerotic aneurysm of the intrathoracic left subclavian artery is presented, with a review of the English-language literature on the subject. PMID- 7877238 TI - Foregut revascularization via retrograde splenic artery perfusion after resection of a juxtaceliac mycotic aneurysm: complicated by pancreatic infarction because of cholesterol emboli. AB - A 66-year-old woman had development of a rapidly enlarging juxtaceliac mycotic aneurysm after therapy for lumbar osteomyelitis and a psoas abscess. The aneurysm was repaired through a thoracoabdominal approach with a Dacron aortic graft sewn end to end to the thoracic aorta and end to side to the infrarenal aorta. Perfusion was restored after oversewing the abdominal aorta above the superior mesenteric artery and oversewing the celiac trunk. After reperfusion the foregut remained critically ischemic despite a patent superior mesenteric artery. Foregut reperfusion was achieved by removing the spleen and anastomosing the distal splenic artery to the aortic graft. Recovery was complicated by infarction of the body of the pancreas because of cholesterol emboli, resulting in a large pleural effusion. After undergoing a subtotal pancreatectomy that preserved the splenic artery, the patient recovered without additional complications. During 8 years of follow-up, the patient has normoglycemia and has had no further infections complications. The distal splenic artery offers an excellent inflow for foregut revascularization; however, the pancreas is intolerant of atheromatous emboli. PMID- 7877239 TI - Abdominal aortic aneurysm repair after pancreaticoduodenectomy. AB - We present two cases of patients with coincidental pancreatic disease and abdominal aortic aneurysm. Initial pancreaticoduodenectomy was followed by staged abdominal aortic aneurysm repair via a retroperitoneal approach in both cases. We recommend the retroperitoneal approach over the transperitoneal approach as an easier and safer method of aortic aneurysmorrhaphy after the Whipple procedure. PMID- 7877240 TI - Re: "Thrombolysis with tissue-plasminogen activator: results with a high-dose transthrombus technique". Thrombolysis Study Group. PMID- 7877241 TI - Regarding "The incidence of deep venous thrombosis in patients undergoing abdominal aortic aneurysm resection". PMID- 7877242 TI - Lipoprotein(a) levels in peripheral atherosclerotic disease. PMID- 7877243 TI - Regarding "Evaluation and performance standards for arterial prostheses". PMID- 7877244 TI - Changes in arterial wall compliance after endovascular stenting. PMID- 7877246 TI - [Revaluation of current antimicrobials. Series 23: aspoxicillin]. PMID- 7877245 TI - [Revaluation of current antimicrobials. Series 22: cefteram pivoxil]. PMID- 7877247 TI - [Revaluation of current antimicrobials. Series 24: imipenem/cilastatin]. PMID- 7877248 TI - [Basic and clinical studies on biapenem (L-627) in obstetrics and gynecology]. AB - We investigated biapenem (BIPM, L-627) a newly carbapenem antibiotic, for its antibacterial activity, tissue penetration, clinical efficacy and bacteriological effect in obstetric and gynecological infections, and obtained the following results. 1. Antibacterial activity: MICs of L-627 against 149 strains isolated from 80 patients in this clinical trial were examined and compared with those of imipenem (IPM) and ceftazidime (CAZ). The MIC50 and MIC90 of L-627 against the isolates were 0.2 and 12.5 micrograms/ml, respectively. Those of IPM were 0.2 and 6.25 micrograms/ml, respectively. The antibacterial activity of L-627 was quite similar to that of IPM, and was superior to that of CAZ. 2. Tissue and retroperitoneal fluid penetration: The peak levels in venous and uterine arterial sera were 24.0 and 26.2 micrograms/ml, respectively, after 300 mg drip infusion. The peak levels in the uterine or adnexal tissues were 2.39-9.60 micrograms/g, and 0.2 microgram/g of L-627 was detected at 275 minutes after administration. Peak levels in retroperitoneal fluid were 8.7 +/- 1.7 micrograms/ml at 1 hour after the completion of 30 minutes drip infusion (300 mg) and 7.9 +/- 0.2 micrograms/ml at 30 minutes after 300 mg 60 minutes drip infusion (300 mg). These levels expected the MICs against main pathogenic organisms. 3. CLINICAL RESULTS: L-627 was given to the following 144 patients (No. of analytical subjects) at a daily dose of 0.3-1.2 g for 2-13 days: intrauterine infections (54), adnexitis (36), parametritis (17), pelvic peritonitis (27), bartholins abscess (6) and other infections (4). The clinical efficacy was 93.1% (134/144) and the eradication rate against isolated organisms was 88.7% (110/124). Side effects were observed in 2 patients: eruption (1) and vomiting with numbness of the tongue (1). Abnormal change in laboratory test results included increase in eosinophils in 1, increase in GOT, GPT and gamma-GTP in 1 and increase in GPT and A1-P in 1, but all of these abnormalities were very mild and withdrawal of the drug was not required. Our results suggest that this drug is useful in the treatment of gynecological infections. PMID- 7877249 TI - [Effect of biapenem (L-627) on fecal flora in gnotobiotic mice and children]. AB - Biapenem (L-627), a novel injectable carbapenem antibiotic, was studied with regard to its effect on mice inoculated with four types of bacteria and on the intestinal flora of pediatric patients. L-627 was given i.m., 40 mg/kg once daily for 5 consecutive days, to mice inoculated enterically with four types of bacteria (Escherichia coli, Enterococcus faecalis, Bacteroides fragilis, and Bifidobacterium breve). Except for a mild decrease in E. coli, there were no major fluctuations in viable bacterial counts in the feces during the treatment. Five children with bacterial infections (3 boys and 2 girls; ages: 1 month to 7 years and 7 months; body weights 4.62-21.8 kg) were given L-627 at 6.0 to 11.7 mg/kg 3 times daily for 7 to 11 days. Among aerobes, although Enterobacteriaceae such as E. coli tended to decrease remarkably in all patients, there was no major change in Enterococcus. Consequently, total aerobe counts did not change significantly in any patient. Among anaerobes, Bifidobacterium, Bacteroides, and Eubacterium, which are the predominant organisms in infants, decreased remarkably in some patients. One of the patients showed a marked decrease in total anaerobe count associated with a change in fecal characteristics (diarrhea). Glucose nonfermenting Gram-negative bacilli or fungi did not become predominant organisms in any patient. Recovery from these changes in the intestinal flora was noted promptly after terminating L-627 treatment. L-627 was detected in the feces of 4 patients during treatment. The fecal concentration ranged from 0.24 to 2.22 micrograms/g. Clostridium difficile was not detected in any patient. Although C. difficile D-1 antigen was observed in 2 patients, it bore no relationship to fecal properties. The results indicated that L-627 had relatively few effects on the intestinal flora compared to other new beta-lactam antibiotics. PMID- 7877250 TI - [Antibacterial activities of a carbapenem antibiotic, biapenem (L-627), against penicillin-resistant Streptococcus pneumoniae]. AB - Antibiotic susceptibilities were evaluated for 48 strains of Streptococcus pneumoniae collected in 1992-1993 at Ichihara City of Chiba Prefecture. Twenty two (46%) of the 48 strains were benzylpenicillin (PCG) insensitive or resistant (PRSP) judged from the MICs of PCG to higher than 0.1 microgram/ml. MICs of piperacillin and cefotaxime increased as the MICs of PCG increased. However, elevations of MICs of imipenem and biapenem (L-627) were small in spite of the increases of MICs of PCG. L-627 was effective in a case of purulent meningitis due to PC-insensitive S. pneumoniae. Thus, L-627 is a candidate to be used in treatment of PRSP infections including purulent meningitis. PMID- 7877251 TI - [Pharmacokinetic and clinical studies on biapenem (L-627) in the pediatric field]. AB - Pharmacokinetic and clinical studies on biapenem (L-627), a newly developed carbapenem, were performed and the following results were obtained. 1. Absorption/excretion: Pharmacokinetics of biapenem was studied in 14 children at doses of 6 mg/kg and 12 mg/kg administered through 30 minutes-drip infusion. Peak plasma levels and plasma half-lives of the 2 doses were 22.5, 29.9 micrograms/ml, and 0.84, 0.85 hours, respectively. Their urinary recovery rates were 54.5 to 76.1% and 37.3 to 59.5%, respectively. Cerebrospinal fluid levels of biapenem in two patients with purulent meningitis were 0.88 and 2.72 micrograms/ml, and the penetration rates were 3.7 to 8.3%. 2. Clinical study: Forty-nine patients were treated with biapenem at doses exceeding 90 to 100 mg/kg/day for purulent meningitis and at doses between 15.0 and 36.0 mg/kg/day for other infections. Biapenem gave "Excellent" or "Good" responses in 48 cases, hence an efficacy rate of 98.0% was obtained. Only one patient with pneumonia showed a fair response. No adverse reactions were observed. Abnormal laboratory test results were noted in 7 patients including elevation of GOT, GPT, and eosinophils. In no cases the treatment had to be discontinued. PMID- 7877252 TI - [Pharmacokinetic, bacteriological and clinical evaluation of biapenem (L-627) in the pediatric field]. AB - Pharmacokinetic, bacteriological and clinical studies on biapenem (L-627), a newly developed carbapenem antibiotic, were performed in the field of pediatrics. 1. Antibacterial activities of biapenem against 54 strains of Streptococcus pneumoniae isolated in 1993 were compared with those of 13 other antibiotics, consisting primarily of beta-lactam compounds. Minimal inhibitory concentrations (MICs) of biapenem were < or = 0.78 micrograms/ml against all strains, and excellent values were obtained even against benzylpenicillin (PCG)-resistant strains. Based on MIC80 values, biapenem, imipenem, and cefuzonam showed highest antibacterial activities, followed by cefotaxime. 2. Blood concentrations and urinary excretion were studied after intravenous drip infusion of 6.0 mg/kg and 6.1 mg/kg of biapenem, given over 30 min., to two children (ages: 4 years and 11 years). Blood drug concentrations were 14.7 and 37.6 micrograms/ml, respectively (mean: 26.2 micrograms/ml), at 30 min. after starting infusion (at completion of infusion). Blood concentrations then declined gradually with half-lives of 0.66 and 1.16 hrs., respectively (mean: 0.91 hrs.). After 5.5 hrs., blood concentrations were no longer measurable in the former and 0.46 micrograms/ml in the latter. Urinary recovery rates of drug in the first 6 hrs. after starting administration were 65.8% and 60.9%, respectively (mean 63.4%). 3. Penetration of the drug to the cerebrospinal fluid (CSF) was studied in 2 patients with purulent meningitis. Biapenem, 31.6 mg/kg, was administered four times daily by 30-min. intravenous drip infusion. CSF concentration 1 hr. after administration was 8.54 micrograms/ml on the day of the start of treatment (day 0), and 3.00, 2.04, 16.1, 4.16, 3.24, and 1.60 micrograms/ml on days 1-7 of treatment, respectively. In a patient similarly administered with the drug at 33.7 mg/kg four times daily, the CSF concentration at 1.5 hrs. after administration was 2.62 micrograms/ml on the next day of the start of treatment. On days 2-7 of treatment, CSF concentrations at 0.5-1 hr. after administration were 4.60, 12.9, 20.6, and 1.32 micrograms/ml, respectively. 4. Clinical efficacy was evaluated in 27 patients with pediatric infections. The dose administered per dosage was 5.2-33.7 mg/kg. Three or four dosages were given daily. The duration of therapy ranged from 3 1/3 to 11 days. Total administered doses were between 0.675 and 20.475 g. Clinical efficacy was evaluated in a total of 24 patients (purulent meningitis 1, acute otitis media 1, acute bronchitis 2, acute pneumonia 19, acute urinary tract infection 1). Responses to treatment were excellent in 14 patients and good in 10 patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7877253 TI - [Studies on the efficacy and safety of biapenem (L-627) against infections in pediatrics]. AB - The efficacy and the safety of biapenem (L-627), a new carbapenem antibiotic, against infections in pediatrics were studied. The obtained results are summarized as follows. 1. L-627 at dose levels of 5.4 mg/kg to 12.4 mg/kg (daily doses of 16.2 mg/kg to 37.2 mg/kg) was administered by intravenous drip infusion 3 times daily for 5 to 7 days to 2 cases of pneumonia, 3 cases of skin and soft tissue infections and 1 case of urinary tract infection for a total of 6 cases. As results, all the cases showed good or better responses including 4 excellent and 2 good results. Bacteriological efficacies in all of the 3 eligible cases were assessed as "eradicated". 2. As for the safety, a decrease in the WBC count and slight elevation of GOT and GPT were observed in 1 case as abnormal changes in the laboratory tests results, only incidence of side effect observed was the eruption in 1 case. 3. The results above indicate that L-627 is useful for the treatment of general infections in pediatrics. PMID- 7877254 TI - [Bacteriological, pharmacokinetic and clinical studies on biapenem (L-627) in the pediatric field]. AB - Antibacterial activities were determined and pharmacokinetics and a clinical studies were performed on biapenem (L-627), a novel parenteral carbapenem antibiotic, in infections in children. The following results were obtained: 1. MICs of L-627 against clinical isolates were as follows: Among Gram-positive bacteria, MICs were 0.78 microgram/ml to > 100 micrograms/ml against 3 strains of methicillin-resistant Staphylococcus aureus (MRSA), and 0.10 microgram/ml to 0.39 microgram/ml against 8 strains of methicillin-sensitive S. aureus (MSSA), MICs against 5 of them were similar to those of imipenem (IPM), and MICs against 3 of them were slightly higher than those of IPM. MICs were < or = 0.025 microgram/ml to 0.39 microgram/ml against 7 strains of Streptococcus pneumoniae, and were similar to those of IPM, and lower than those of ceftazidime (CAZ) and piperacillin (PIPC). Among Gram-negative bacteria, MICs were 0.78 microgram/ml and 3.13 micrograms/ml against 2 strains of Haemophilus influenzae, and were similar to those of IPM. 2. Maximum plasma concentrations determined by the bioassay method after intravenous infusion of L-627 over 30 minutes at doses of 6.0 and 12.0 mg/kg, respectively, in 2 different pairs of 2 children each (total 4 cases) were observed upon completion of the treatment. Maximum concentrations at a dose of 6.0 mg/kg were 28.8 micrograms/ml and 24.6 micrograms/ml, and at a dose of 12.0 mg/kg were 65.4 micrograms/ml and 39.6 micrograms/ml, exhibiting a dose response. Plasma half lives in the beta phase were 0.97 and 1.20 hours at 6.0 mg/kg, and 0.72 and 0.94 hour at 12.0 mg/kg. Plasma concentrations determined by the HPLC method were lower than those determined by the bioassay. 3. Urinary excretion rates in the first 5.5 hours after the 6.0 mg/kg dose were 81.4 and 75.3%, and after the 12.0 mg/kg dose were 91.0 and 73.8%, and these values were higher than those obtained using HPLC. 4. Concentrations of L-627 in cerebrospinal fluid were determined in 2 cases of purulent meningitis. In one case, 30.3 mg/kg of L-627 was infused intravenously over 30 minutes and concentrations on days 1, 3, 7 and 14 observed at 60, 60, 45 and 45 minutes after respective dosages were 7.60, 1.30, 1.42 and 0.38 microgram/ml. Cerebrospinal fluid-plasma concentration ratio was determined on days 7 and 14 to be 5.5 and 1.2% respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7877255 TI - [Antibacterial activities of cefetamet against clinically isolated strains from community acquired respiratory tract infections (II)]. AB - Antibacterial activities of cefetamet (CEMT) against clinically isolated strains from patients with community acquired respiratory tract infections were compared to those of other oral beta-lactam antibiotics in the period from January to March 1994. The following results were obtained. 1. CEMT showed strong antibacterial activities against three major pathogens causing community acquired respiratory tract infections, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae. However, antibacterial activities of CEMT against benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) and PCG-resistant S. pneumoniae (PRSP) were slightly weaker than of those of some the reference antibiotics. 2. No MIC value changes of CEMT were observed from year to year against Moraxella subgenus Branhamella catarrhalis and Klebsiella pneumoniae. PMID- 7877256 TI - [A clinical study on chemotherapies for chorioamnionitis]. AB - Effects of imipenem/cilastatin (IPM/CS) therapy, flomoxef (FMOX) therapy and combined ceftazidime + aspoxicillin (CAZ/ASPC) therapy as initial therapies for chorioamnionitis were assessed clinically. 1. The subjects were 49 women with threatened abortion and 29 with premature rupture of membranes (PROM), complicated in all cases by chorioamnionitis. The inflammation was treated with IPM/CS in 19 patients, FMOX in 39, CAZ in 11, and CAZ/ASPC in 9. 2. The response rate to therapy for chorioamnionitis was 95.9% (47/49) in the threatened abortion group. Of the 49 patients in this group, 16 (32.7%) underwent premature labor. Of the therapies administered, IPM/CS tended to prevent premature labor more frequently than did any other therapy. The latent period (from rupture of membranes to delivery) was equal to or longer than 7 days in the PROM group. The percent prolongation of the latent period in these patients (55.5%) was significantly greater than that previously obtained with penicillin therapy. 3. The bacterial elimination rate was 50.9% (29/57). Of the 36 bacterial isolates, 66.7% were Gram-positive bacteria. The bacteriological efficacy rate was 89.7% (26/29). These results suggest that antibacterial agents effective against Gram positive bacteria should be selected for treatment of chorioamnionitis, and that IPM/CS therapy is particularly useful considering the drug's good transfer into amniotic fluid and its antibacterial spectrum. PMID- 7877257 TI - Analysis of the neurofibromatosis 2 gene in human breast and hepatocellular carcinomas. AB - The neurofibromatosis 2 gene (NF2) mapped to chromosome 22q is a recently isolated tumor suppressor gene that participates in the tumorigenesis of cells of embryonic neural crest origin. The structural similarities between the NF2 product, merlin-schwannomin, and the band 4.1 family raise the possibility that merlin may participate in a wide range of cell activities, in which the cytoskeleton latticework has important roles to play. In order to examine the significance of NF2 in general carcinogenesis, comprehensive analyses of 68 cases of breast carcinoma, which shows frequent loss of heterozygosity at chromosome 22, and 48 hepatocellular carcinomas of different histological grade were performed. No mutation was detected by the polymerase chain reaction-single strand conformation polymorphism method for six exons of NF2 in any of the cases examined, suggesting that NF2 may be less important in the tumorigenesis of breast and liver cancers than in that of cancers originating from the neural crest. PMID- 7877258 TI - Eyelid metastasis from breast cancer showing marked response to chemotherapy. AB - A patient with recurrent breast cancer, who was diagnosed with eyelid metastasis as a part of systemic metastases and in whom systemic chemotherapy was markedly effective, is reported. A 50-year-old woman underwent a radical mastectomy for stage II breast cancer in October, 1988. Histologically, the tumor was invasive lobular carcinoma. In October, 1993, the patient consulted our hospital complaining primarily of swelling of the left eyelid and restriction of movement in the left eye. Metastasis from breast cancer was diagnosed on eyelid biopsy. On further examination, metastases were detected in the liver, bone, orbit, peritoneum and pleura. Systemic combined chemotherapy consisting of cyclophosphamide, adriamycin and 5-fluorouracil was administered intravenously at intervals of three weeks. Complete responses were obtained in the eyelid and peritoneal metastases after three courses, and in the liver metastasis after five courses. Partial responses were also observed in the bone and pleural metastases. The incidence of eyelid metastasis from breast cancer is very low, one case only having been previously reported in Japan and 34 cases abroad. Most of these cases were treated locally by surgical resection or radiotherapy, but the mean survival period was only 14 months, ranging from two months to four years. Eyelid metastasis from breast cancer should be regarded as a manifestation of systemic spread of the tumor and, in principle, treated by systemic therapy. PMID- 7877259 TI - Fibromatosis of the breast: a case report. AB - Fibromatosis of the female breast is rare. We dealt with a recurrent case of fibromatosis four months after a wide excision of the tumor. It was difficult to differentiate the tumor from carcinoma and only a pathological examination could lead to the final diagnosis. Ultrasonographic findings are so characteristic that we would like to emphasize the usefulness of ultrasonography not only in distinguishing between recurrence and operative scar but also in defining the diagnosis as fibromatosis of the breast. PMID- 7877260 TI - Pulmonary metastasis of renal cell carcinoma resected sixteen years after nephrectomy. AB - A 50-year-old man underwent a left nephrectomy for renal cell carcinoma of the clear cell type in February, 1978. He was examined using computed tomography in September, 1993, and was found to have a small coin lesion in his right lung. A fine needle aspiration biopsy failed to disclose any tumor cells. He underwent a video-assisted thoracoscopic biopsy of the right lung in February, 1994, 16 years after his nephrectomy. The resected specimen contained a coin lesion measuring approximately 1 cm in diameter, and the lesion was microscopically diagnosed as a renal cell carcinoma of the clear cell type metastatic to the lung. The patient is doing well with no signs of re-recurrence six months after the resection of the metastatic lesion. To our knowledge, the time interval between his nephrectomy and resection of the metastatic lesion is the longest ever reported in Japan. PMID- 7877261 TI - [Necretomy and prolonged local postoperative lavage in the surgery of necrotic pancreatitis]. AB - Over an 8-year period, sixty-one patients with mean age 52.5 years are operated on for necrotic pancreatitis in the clinic of emergency surgery at the Faculty Hospital "Queen Giovanna"--Sofia. The initial prognosis of the severity of disease scores 4.5 points average according to Ronson's rating system. The indications for operative treatment are clinically determined and further specified by ultrasonographic echo-ranging and computerized axial tomography. Necrectomy associated with prolonged local postoperative lavage are used as a method considered the most adequate from tactical viewpoint. The criteria for this particular therapeutic approach are substantiated. At 19.6 per cent lethality the postoperative results are estimated as satisfactory, and fully consistent with worldwide experience along this line. PMID- 7877262 TI - [Our experience with the diagnosis and treatment of biliary pancreatitis]. AB - The diagnostic and therapeutic problems faced during treatment of thirty-nine patients presenting biliopancreatitis (BP) are discussed. BP diagnosis is made on the ground of clinical picture, laboratory indicators, abdominal ultrasonography, intraoperative cholangio-pancreatography and cholangioscopy. Patients with cholelithiasis (ChL) of long-standing in the previous history are predominant, with the age group exceeding 50 years of age being most numerous, and the female gender prevailing. All patients undergo conservative pre- and postoperative treatment. Operative treatment in BP is performed as an emergency intervention. Cholecystectomy is done in all cases, and in 56.3 per cent of them it proves sufficient to promote a favourable outcome of the pathologic condition. External or internal drainage of the choledochus is necessitated in the presence of definite indications (obstruction of extrahepatic biliary ducts and pancreas documented by operative cholangiography, choledochoscopy and probing). Dilatation of the papillary sphincter is carried out in five patients (12.8 per cent) because of partial papillary stenosis. The destructive forms of pancreatitis are treated by gland draining in conjunction with necrectomy and drainage of the extrahepatic biliary ducts. A correlation is established between the incidence of destructive forms of pancreatitis and therapeutic results, on the one hand, and timing of the operative intervention, on the other. Operative management of BP is a method of choice insofar as it contributes to the complex and thorough treatment of the condition. Preoperative BP diagnosis is still a problem not well enough clarified which leads to delayed operation with an adverse impact on the prognosis of the disease. PMID- 7877263 TI - [The surgical treatment of malignant tumors of the adrenal glands]. AB - Thirty patients presenting malignant adrenal tumors of which 19 women aged 3-70 years, and eleven men with ages ranging from 5 to 70 years, are operated in the clinic of endocrine surgery over the period 1965 through 1992. In 16 cases the neoplasm is located on the right side, and in thirteen--on the left side. In 26 patients it is a matter of primary tumor, and in four--metastasis. Ten patients present the clinical picture of corticosteroma, three--pheochromocytoma, and four -corticoandrosteroma. The neoplastic mass extirpated weighs from 69 to 2050 g, necessitating the performing of nephrectomy in six instances, and splenectomy--in two. The operative technique used, intra- and postoperative complications, and the early and late postoperative survival in the series reviewed are analyzed. PMID- 7877265 TI - [A pathogenetic approach to the surgical treatment of large postoperative hernias]. AB - Intractable intraoperative retraction of the abdominal musculature, associated with large postoperative hernias, give rise to reduced abdominal cavity volume, increase of intra-abdominal pressure and pulling along the suture line. These are factors considered as preconditions of the development of postoperative complications and recurrences. Experience with intraoperative facilitation by the application of relief incisions on the aponeurosis of the external oblique abdominal muscles according to Borodin et al during restoration of the abdominal wall continuity at the site of defect is shared. The procedure described is used in the operative management of ten patients presenting large postoperative hernias following superior median laparotomy, in two of them recurrent, one female patient following Rio Branco's operative access, and two cases with recurrent hernia after appendectomy. A complication--operative wound hematoma--is recorded in a single female patient only. The uneventful postoperative course, and the absence of recurrences over periods ranging from several months to two years, are good reasons to discuss the experience so far accumulated, and recommend the method for the practice. PMID- 7877264 TI - [Radionuclide ventriculography in the diagnosis of a postinfarct aneurysm and the evaluation of its impact on left ventricular function]. AB - This is a report on thirty-four patients subjected to radionuclide ventriculography because of suspected post-infarction aneurysm. To discover eventual kinetic disorders, apart from visual assessment of the wall kinetics, amplitude-phase analysis is also employed. The sensitivity of the method is compared with that of bi-dimensional echocardiography. The assessment of post infarction left ventricular function by either of the methods is also compared. A correlation is established between left ventricular area involved by kinetic disorders, and reduction of the radionuclide total ejection fraction. The values of the latter, estimated echocardiographically, are consistently elevated. PMID- 7877266 TI - [The use of polypropylene sheet in primary hernioplasties in the inguinal area]. AB - In the light of updated discussion of biologic and biochemical aspects in the etiology and pathogenesis of inguinal hernia, its basic subdivision into congenital and acquired forms is considered as the most expedient. Acquired hernias, unlike congenital ones, are produced by collagen metabolism impairment, leading in turn to reduction of its deposition in the connective tissue subsequent to collagenolysis prevailing over collagen forming processes. The early results of the application of polypropylene cloth in thirty primary hernioplastic procedures are analyzed. All patients are followed up over periods ranging from 3 to 36 months. The obtained results are compared with those in another group of thirty patients, subjected to inguinal canal reconstruction after the method of Bassini-Postemsky (a technique most frequently used in this country) performed by the same surgical team. PMID- 7877267 TI - [Diagnostic laparoscopy and laparoscopic surgery--their development and outlook]. AB - Laparoscopy was introduced in the beginning of the 20 century. It is developed as a diagnostic procedure, often combined with biopsy. In the 80 ies the laparoscopy came in surgery, first in appendectomy, later in cholecystectomy, where it achieved exclusive appliance and became an alternative method of conventional surgery. In the beginning of 90-ies the laparoscopic surgery treats more and more of diseases of abdominal surgery. PMID- 7877268 TI - [Acute emphysematous cholecystitis--2 clinical cases]. PMID- 7877269 TI - [A case of multiple echinococcosis with a rare location of clinical and therapeutic interest]. PMID- 7877270 TI - [2 cases of primary carcinoid complicated by ileus]. PMID- 7877271 TI - [Mucormycosis of the orbit and paranasal sinuses]. PMID- 7877272 TI - [A new approach to Cooper's ligament in hernioplasty of the inguinal canal]. PMID- 7877273 TI - [Postoperative choledochoscopy (transparietal, trans-drainage choledochoscopy)]. AB - Residual biliary stones can be treated with: direct dissolution; endoscopic papillotomy and extraction; extracorporeal lithotripsy, repeated operations, removal via T-tube tract. Authors describe the employment in clinical practice (on 3 patients) the original method of extraction of residual common bile duct stones with the help of fiber choledochoscope introduced through the drainage channel in the common bile duct. Pros and coins of this method are discussed in comparison with the routine methods and it is recommended to be used in the early postoperative period in patients with T-tube drainage. PMID- 7877274 TI - [Diagnosis and the therapeutic strategy in gallbladder carcinoma]. AB - Authors analyse the results of the treatment of 39 patients with gallbladder carcinoma for period of 6 years (1987-1992). In relation to all the patients with gallstone disease treated in the clinic for the some period, patients with gallbladder carcinoma were 2.9%, and respectively 4.7% of all biliary operations. Gallstone disease was diagnosed in 28 patients (72%) with gallbladder carcinoma. Important for diagnosis were characteristic clinical signs and symptoms, supplemented by imaging methods (most important ultrasonography--performed in 34 patients). Radical operations were performed in 11 patients (28%), with one year survival rate 82% (9 patients). Authors discuss the relation between the clinical stage of gallbladder carcinoma, performed operation and survival rate in operated patients. PMID- 7877275 TI - A survey of rural parents' attitudes toward sexuality education. AB - Although local attitudes and values influence a community's support for sexuality education, educators rarely assess local views in a systematic way. A survey of community parents provides a simple, relatively inexpensive way to assess support for sexuality education and strengthen the school's leadership in implementing an effective curriculum. This paper describes the use of a parent survey for building a comprehensive sexuality education program in a rural community. Most respondents supported sexuality education even for the elementary grades. Compared to a survey conducted 10 years earlier, respondents were significantly less confident of themselves and other parents as sexuality educators. Attitudes varied by demographic characteristics. Using these findings, the paper illustrates how the strategic use of a parent survey can strengthen school-based sexuality education by minimizing potential controversy and building a broader base of active community support and involvement for sexuality education. PMID- 7877276 TI - Guidelines for school health programs to prevent tobacco use and addiction. Centers for Disease Control and Prevention (U.S.). AB - Tobacco use is the leading cause of preventable death in the U.S. Most daily smokers (82%) began smoking before age 18, and more than 3,000 young persons begin smoking each day. School programs designed to prevent tobacco use could become one of the most effective strategies available to reduce U.S. tobacco use. The following guidelines summarize school-based strategies most likely to be effective in preventing tobacco use among youth. They were developed by CDC in collaboration with experts from 29 national, federal, and voluntary agencies and with other leading tobacco-use prevention authorities to help school personnel implement effective tobacco-use prevention programs. These guidelines are based on an in-depth review of research, theory, and current practice in school-based tobacco-use prevention. The guidelines recommend that all schools: a) develop and enforce a school policy on tobacco use, b) provide instruction about the short term and long-term negative physiologic and social consequences of tobacco use, social influences on tobacco use, peer norms regarding tobacco use, and refusal skills, c) provide K-12 tobacco-use prevention education, d) provide program specific training for teachers, e) involve parents or families in support of school-based programs to prevent tobacco use, f) support cessation efforts among students and all school staff who use tobacco, and g) assess the tobacco-use prevention program at regular intervals. PMID- 7877277 TI - Discriminating suicide ideation among high-risk youth. AB - This study examined the hypothesis that among one group of high-risk youth- potential high school dropouts--key psychosocial factors would distinguish adolescents endorsing high suicide ideation from those who do not. Survey data compared high-risk youth with high suicide ideation (n = 43) with randomly selected samples of high-risk (n = 43) and "typical" youth (n = 42) without high suicide ideation. Repeat sampling of comparison groups verified results. Compared to high-risk and typical youth without suicide ideation, high-risk youth with high suicide ideation reported more psychosocial distress, problems with drug involvement, and disrupted family relations. They also described more unmet school goals and perceived a greater likelihood of dropping out of school. Discriminant analysis revealed that depression and low self-esteem were most effective in distinguishing between high-risk youth with and without high suicide ideation; family strain, anger, stress, and drug involvement also were differentiating factors. Implications for school-based screening and prevention programs are discussed within the context of the findings. PMID- 7877278 TI - A preliminary study of potential dietary risk factors for coronary heart disease among Chinese American adolescents. AB - This study investigated dietary knowledge, attitudes toward diet, behavioral factors affecting diet, and dietary patterns between American Chinese middle school students and Chinese middle school students living in China. Significant differences occurred in these variables between the two groups of students. Chinese students living in China had less knowledge and a less favorable attitude. However, they exhibited more positive behavioral factors affecting diet which include culture, religion, customs, economic factors, beliefs, and values. As for the dietary pattern, Chinese student living in China consumed less meat, dairy products, fat, sweets and snacks, and fast foods, and consumed more fruits, vegetables, and starch. PMID- 7877279 TI - Correlates and consequences of early initiation of sexual intercourse. AB - This cross-sectional analysis of the 1991 CDC Youth Risk Behavior Survey explored factors associated with an early age at first sexual intercourse. Almost 18% of White males, 49% of Black males, 5% of White females and 12% of Black females were sexually active before age 13. Carrying a weapon to school, fighting, and early (< age 13) experimentation with cigarettes and alcohol were associated with early initiation of sexual activity for all four race and gender groupings. Those initiating sexual activity early had greater numbers of partners but were 50% less likely to use condoms regularly and were two-seven times more likely to have been pregnant or caused a pregnancy. Females who initiated sexual activity early were more likely to have had a sexually transmitted disease (STD). Interventions to postpone sexual activity need to be tailored to the ethnic and gender differences observed in these analyses. Interventions must begin before age 13 and should be comprehensive school-based efforts. PMID- 7877280 TI - Telling a coherent story of health and disease. PMID- 7877281 TI - Use of cardiopulmonary resuscitation by North Carolina day care providers. PMID- 7877282 TI - Linguistic performance and regional cerebral blood flow in persons who stutter. AB - In a series of studies regarding CNS dysfunction in stuttering, we have examined linguistic and motoric performance in the context of measures of brain function. Previous studies of adults with developmental stuttering identified alterations in brain function (metabolic and electrophysiologic) in cortical regions implicated in models of speech motor control and language processing. We also identified a sub-group of these subjects who exhibited linguistic performance deficits related to speech performance deficits. The present study examined the hypothesis that adults who stutter and who show linguistic performance deficits will also show metabolic alterations in cortical regions classically related to language processing, whereas adults who stutter but who do not show linguistic performance deficits will not show these cortical metabolic alterations. Significant relative blood flow asymmetry (left < right) was observed in middle temporal and inferior frontal cortical regions only for adults who both stuttered and showed linguistic performance deficits. Results support models that explicitly recognize that efficient integration of linguistic, motoric, and cognitive processes is critical to the production of oral/verbal fluency and to understanding sources of fluency failure. PMID- 7877283 TI - Respiratory and laryngeal measures of children and women with bilateral vocal fold nodules. AB - Simultaneous assessment of laryngeal and respiratory function was completed on 8 children and 10 women with bilateral vocal fold nodules and compared to that of 8 children and 10 women with normal voice production. Laryngeal function for the individuals with bilateral vocal fold nodules was characterized by significantly higher peak, alternating, and minimum glottal airflow. The presence of the high glottal airflow was accompanied by a significantly larger lung volume excursion. Both the children with nodules and those with normal voice showed laryngeal and respiratory function differences when compared to adults. All subject groups demonstrated appropriate laryngeal and respiratory function when increasing intensity from comfortable to loud speech. Simultaneous measurement of laryngeal and respiratory function using a multidimensional analysis of voice production is advocated in the evaluation of voice disorders because it can provide specific information regarding which of the subsystems of voice production are compromised. PMID- 7877284 TI - A control/experimental trial of an operant treatment for early stuttering. AB - A preliminary study (Onslow, Costa, & Rue, 1990) suggested that a parent conducted program of verbal response-contingent stimulation would be an effective treatment for stuttering children younger than 5 years. The present study was designed to expand those preliminary findings by using a larger group of children and by comparing them to a control group of children. Twelve children in the experimental group achieved median percent syllables stuttered (%SS) scores below 1.0 for a 12-month posttreatment period. The children's treatments were completed in a median of 10.5 1-hour clinic sessions and a median of 84.5 days from the start of treatment. The majority of parents of the control children withdrew from the study and elected to have treatment begin for their child. These results suggest that the program may be a cost-effective method for managing a clinical caseload of stuttering children younger than 5 years. It is suggested that controlled clinical trials cannot be used validly or ethically to determine the number of cases of early stuttering who recover without formal intervention. PMID- 7877285 TI - Levator veli palatini muscle activity in relation to intraoral air pressure variation. AB - The purpose of this investigation was to study the operating range of the levator veli palatini muscle for a nonspeech task (blowing) and to determine where in that range levator activity for speech lies. Ten adult subjects without speech or velopharyngeal abnormalities participated. Levator EMG activity for speech occurred in the lower region of the total range for blowing. In two subsequent experiments involving a subset of 4 subjects, it was found that overall effort may have had a small effect on levator activity apart from its role in velopharyngeal closure for aerodynamic purposes. The results of the main experiment are discussed in relation to the concept of threshold of fatigue as it may influence velopharyngeal control mechanisms. PMID- 7877286 TI - Intelligibility and nonspeech orofacial strength and force control following traumatic brain injury. AB - Objective measures of nonspeech orofacial strength and force control were obtained for 20 individuals with traumatic brain injury. The dynamic and static force generating abilities of the upper lip, lower lip, tongue, and jaw were assessed. Based on sentence intelligibility scores, the subjects were divided into two groups, more and less intelligible. Force measures included reaction time, slope, derivative, peak overshoot, and first- and second-half mean hold and standard deviation. Groups differed only in the ability to sustain the 2 N force level with the tongue. Other potential contributors to the differences in intelligibility are discussed. PMID- 7877287 TI - Speech rates and turn-taking behaviors of children who stutter and their fathers. AB - Paralinguistic behaviors, including speech rates and turn-taking behaviors, of boys who stutter and boys who do not stutter and their fathers were investigated. Subjects were 11 boys who stutter (mean age = 5:1) and their fathers and 11 age matched (+/- 3 months) nonstuttering boys (mean age = 5:1) and their fathers. Spontaneous conversational speech was obtained from each father and son during approximately 45 minutes of videotaped free play in a clinic setting. Measures of overall, articulatory, and dyadic speaking rates, interruptions, response time latencies, and disfluency characteristics were derived using the videotapes and computer-assisted analyses of the acoustic signal from each conversational sample. Two-factor repeated measures ANOVAs were performed on each of the paralinguistic variables for the 11 sets of age-matched father-son pairs. Fathers produced faster speaking rates, higher frequencies of interruptions and shorter response time latencies than sons. No significant differences were found in comparisons of the two groups of fathers or of the two groups of children for any of the paralinguistic behaviors. A significant positive correlation was found between the SSI scores of children who stutter and the dyadic speaking rates of these children and their fathers. Results partially extend those of Kelly and Conture (1992) for mothers and children, but some potentially important differences emerge between fathers' and mothers' (para)linguistic behaviors in interaction with their children. PMID- 7877288 TI - Time-interval measurement of stuttering: effects of training with highly agreed or poorly agreed exemplars. AB - This study required six groups of judges, three experimental groups and three control groups (all n = 5), to categorize consecutive 5.0-sec speech intervals as Stuttered or Nonstuttered on four judgment occasions. Between the second and third occasions, each experimental group was trained to categorize correctly one of three sets of speech intervals: agreed intervals, which had been unanimously prejudged to be Stuttered or Nonstuttered; disagreed intervals, which had been prejudged to be Stuttered by approximately half of a large group of judges; or randomly selected intervals, including both agreed and disagreed intervals. Results replicated and extended an earlier finding of improved interjudge agreement for judges trained with highly agreed intervals (Ingham, Cordes, & Gow, 1993): Training with highly agreed intervals was shown to be more effective than equivalent exposure to those intervals without feedback, and training with highly agreed intervals was shown to be more effective than training with, or exposure to, poorly agreed or randomly selected intervals. PMID- 7877289 TI - Perceptual rankings of speech quality produced with one-way tracheostomy speaking valves. AB - Perceptual speech quality rankings, mechanical functioning, and maintenance of respiration as measured by oxygen saturation were determined for four different one-way tracheostomy speaking valves. Results indicated significant differences in speech quality rankings, with the Montgomery and Passy-Muir valves ranked significantly better than the Kistner and Olympic valves, and the Olympic valve ranked significantly better than the Kistner valve. The Passy-Muir valve was identified with the best speech quality most often by both listeners and subjects, and exhibited the fewest clinically relevant mechanical problems. Maintenance of respiration was not affected by use of any of the valves studied. PMID- 7877290 TI - Effect of frequency-altered feedback on stuttering frequency at normal and fast speech rates. AB - The purpose of this study was to determine the effect of the magnitude and direction of the frequency shift of frequency-altered auditory feedback (FAF) on stuttering frequency at both normal and fast speech rates. Twelve adult male and 2 adult female subjects who stutter read 10 different passages at either a normal or fast speech rate under nonaltered auditory feedback (NAF) and each of four FAF conditions in which the feedback signal was shifted: up one-half octave; up one octave; down one-half octave; and down one octave. Mean stuttering frequency for NAF was significantly higher than mean stuttering frequencies for all FAF conditions (p < 0.05). There were no statistically significant differences between the FAF conditions (p > 0.05). Subjects exhibited significantly more disfluencies under the fast speech rate condition relative to the normal speech rate condition. Future research should examine the relationship between frequency shifts of less than one-half octave and stuttering amelioration. PMID- 7877291 TI - Generalized effects of enhanced Milieu teaching. AB - The primary and generalized effects of Enhanced Milieu Teaching were examined with six preschool children with significant language delays. In a multiple baseline design across children, trainers implemented the naturalistic language intervention during play-based interaction sessions in the children's preschool classrooms. Children systematically increased their use of targeted language skills during the intervention sessions, and these changes were maintained when the treatment was discontinued. Generalized changes in children's communication resulting from the intervention were examined with untrained teachers, peers, and parents. Some generalization to untrained partners was observed for all children. Correlational analyses indicated that greater numbers of child utterances and greater diversity in vocabulary were associated with increased talking and mands for verbalization presented by partners. PMID- 7877292 TI - A 28-year follow-up of adults with a history of moderate phonological disorder: educational and occupational results. AB - The present investigation is a follow-up to a longitudinal study involving approximately 400 normally developing children begun in 1960. From this large database, two groups of subjects (now aged 32-34) were asked to participate in the present project: (a) a group of 24 adults with a documented history of a moderate phonological/language disorder that persisted through at least the end of first grade (probands), and (b) a group of 28 adults from the same birth cohort and schools who were known to have had at least average articulation skills over the same period (controls). As part of a larger project, these adults were interviewed about their educational and occupational accomplishments and those of their siblings. Results revealed that, in comparison to control subjects, the proband adults reported that they had received lower grades in high school, required more remedial academic services throughout their school careers, and completed fewer years of formal education. Occupationally, although the groups did not differ in employment status, the proband subjects tended to occupy jobs considered semiskilled or unskilled with a much greater frequency than both the control subjects and their gender-matched siblings. When asked to indicate general satisfaction with educational and occupational outcomes, however, subjects in both groups tended to rate themselves as either "very" or "fairly" satisfied. PMID- 7877293 TI - Storytelling in Chippewa-Cree children. AB - The structure and content of self-generated narratives were compared for 20 traditional and 20 nontraditional Chippewa-Cree children in four age groups (5, 7, 9, and 11 years). A majority of the stories contained temporally and causally related events and goal-based action. MLT-unit of the narratives was longer and highly structured stories were constructed more frequently with increasing age. The two traditionality groups differed developmentally in their use of obstacles and causally connected episodes. The stories of 11-year-old traditional children were significantly more likely to contain these elements than their 5-year-old counterparts, whereas similar comparisons for nontraditional children revealed no such developmental change. In terms of story content, intrapersonal obstacles were found to be employed by the oldest groups only and were used more frequently by these Chippewa-Cree children than had been previously reported (e.g., Stein, 1988). Several later-developing aspects of story content were identified that seemed to reflect a Cree cultural influence. These results provide evidence for the use of episodic structure by Chippewa-Cree children, but suggest that the developmental course for particular story structure and content can vary as a function of culture. PMID- 7877294 TI - Sequential recall in individuals with Down syndrome. AB - This study investigated whether memory for item order is selectively impaired in a group of individuals with Down syndrome. The ability to recall correctly ordered information was examined using two auditory tasks--narrative recall (Time 1) and digit span (Time 2)--and a nonverbal, visual task (Time 2) on which mental age (MA) matching was partially determined. Although subjects with Down syndrome recalled significantly less information than MA-matched controls on both auditory tasks, replicating previous findings of auditory memory span deficits, no differences in the ordering of recalled information were found. Nor did the groups differ in the relative frequency of ordering errors in the visual task. Neither a pervasive deficit in sequential processing nor a specific difficulty in recalling the order of information is supported. Alternative accounts are discussed. PMID- 7877295 TI - Use of phonological information in a word-finding treatment for children. AB - Two children with word-finding deficits characterized largely by semantic substitutions participated in a treatment involving phonological information about target words. The treatment was motivated by models of naming where semantic information and phonological information are stored in independent ordered components. Given such models, it is possible to characterize some semantic word-finding substitutions as well as phonological word-finding substitutions as the result of breakdown at the level of the phonological output representation. The treatment was organized according to a single-subject multiple baseline design across behaviors and subjects. As hypothesized, the phonologically based treatment resulted in reduction not only of occasional phonological word-finding substitutions but also of the large number of semantic word-finding substitutions displayed during baseline and control measures of confrontation naming. In light of these data, the possible source of word-finding breakdowns in these children is explored. PMID- 7877296 TI - Duration of function-word vowels in mothers' speech to young children. AB - The purpose of this investigation was to determine whether function words are lengthened in certain phrase positions in mother-to-child speech. Twenty-two mother-child dyads served as subjects. All children (ages 1:5 to 2:2) had a mean length of utterance between 1.0 and 1.5 morphemes. Each mother was asked to read five experimental stories aloud to her child and to an adult. The durations of seven function-word vowels in these stories were examined. Each word appeared in three phrase positions (phrase-initial, phrase-medial, and two types of phrase final). Function-word vowels in initial and medial positions did not differ significantly in adult-directed and child-directed speech. In contrast, function word vowels in final position were significantly longer in mothers' speech to their children. PMID- 7877297 TI - Learning and generalization components of morphological acquisition by children with specific language impairment: is there a functional relation? AB - Children with specific language impairment (SLI) have particular difficulty acquiring bound morphemes. To determine whether these morphological deficits spring from impairments of rule-induction or memory (storage/access) skills, 25 preschool-age children with normal language (NL) and 25 age-matched children with SLI were presented with a novel vocabulary and novel bound-morpheme learning task. A chi square analysis revealed that the children with SLI had significantly lower vocabulary learning levels than NL children. In addition, there was tentative evidence that a dependency relationship existed in some children between success in vocabulary learning and proficiency in generalizing a trained bound morpheme to untrained vocabulary stems. These findings are predicted by the storage/access but not the rule-induction theory of specific language impairment. They suggest that intervention targeting bound-morpheme skills acquisition in children with SLI might include attention to vocabulary development. PMID- 7877298 TI - Comparison of conversational-recasting and imitative procedures for training grammatical structures in children with specific language impairment. AB - The recent literature on language intervention has become increasingly focused upon developing treatments that more closely parallel normal language acquisition. However, there have been relatively few reports that directly compare imitative procedures to conversational-interactive interventions. The purpose of the present study was to compare the relative effectiveness of imitative intervention and conversational recast language intervention applied to a wide range of grammatical morpheme and complex sentence targets in 21 children with specific language impairment. The results indicated that although both kinds of treatments were effective in triggering acquisition of most targets, consistently fewer presentations to first spontaneous use were required in the conversational procedure. In addition, the transition from elicited production to generalized spontaneous production was more rapid under conversation-interactive treatment. Finally, although imitation treatment was more effective in generating elicited production, a significantly greater number of spontaneous productions occurred under the conversational training procedures. The theoretical and applied ramifications of these findings are discussed. PMID- 7877299 TI - Effect of otitis media with effusion on comodulation masking release in children. AB - This study investigated comodulation masking release (CMR) in a group of children with a history of otitis media with effusion (OME) and a control group of children with no known history of ear disease. CMR was measured both in a monotic condition and in a dichotic condition (where comodulated flanking bands were added to the ear contralateral to the signal). CMR was measured before the insertion of pressure equalization tubes, approximately 1 to 3 months after surgery, and approximately 6 to 8 months after surgery. The results indicated that monotic CMRs were reduced in children who had hearing loss due to OME. Furthermore, the monotic CMR remained abnormally small even when threshold had returned to normal for 1 to 3 months. The monotic CMR was essentially normal 6 to 8 months following surgery. No differences were found between the two groups of children for the dichotic CMR. PMID- 7877300 TI - Prediction of asymptotic threshold shift caused by hearing aid use. AB - This study used a well-verified mathematical model to predict asymptotic temporary threshold shift (ATS) caused by hearing aid use. The model determined the amounts of ATS to be expected if real ear insertion gains (REIGs) recommended by the current National Acoustic Laboratories (NAL) procedure are used. It also determined the consequences of use of excess REIG and of high input levels to hearing aids. If recommended REIGs are used and input levels are normal (average A-weighted input levels of about 61 dB SPL), ATS is unlikely to occur for clients who have typical audiograms with three-frequency average pure-tone thresholds (PTAs) less than 60 dB HL. For people with PTAs greater than 60 dB HL, small amounts of ATS can be expected to occur during hearing aid use, but these amounts of ATS are safe, that is, unlikely to be associated with permanent threshold shift (PTS) for individuals with all PTAs except those greater than about 100 dB HL. If REIGs are 15 dB greater than those recommended, the amounts of ATS will be unsafe for people with PTAs greater than about 80 dB HL. It appears unwise for clients who have this degree of hearing loss to use excess REIG. The use of excess REIG in high ambient levels of sound (average A-weighted input levels of about 75 dB SPL) is likely to cause PTS for hearing aid users with PTAs of about 50 dB HL or greater. Clients who prefer to use excess REIG should therefore avoid high ambient sound levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877301 TI - Hemodynamic and physiologic changes during support with an implantable left ventricular assist device. AB - To evaluate hemodynamic effectiveness and physiologic changes on the HeartMate 1000 IP left ventricular assist device (Thermo Cardiosystems, Inc., Woburn, Mass.), we studied 25 patients undergoing bridge to heart transplantation (35 to 63 years old, mean 50 years). All were receiving inotropic agents before left ventricular assist device implantation, 21 (84%) were supported with a balloon pump, and 7 (28%) were supported by extracorporeal membrane oxygenation. Six patients died, primarily of right ventricular dysfunction and multiple organ failure. Nineteen (76%) were rehabilitated, received a donor heart, and were discharged (100% survival after transplantation). Pretransplantation duration of support averaged 76 days (22 to 153 days). No thromboembolic events occurred in more than 1500 patient-days of support with only antiplatelet medications. Significant hemodynamic improvement was measured (before implantation to before explantation) in cardiac index (1.7 +/- 0.3 to 3.1 +/- 0.8 L/min per square meter; p < 0.001), left atrial pressure (23.7 +/- 7 to 9 +/- 7.5 mm Hg; p < 0.001), pulmonary artery pressure, pulmonary vascular resistance, and right ventricular volumes and ejection fraction. Both creatinine and blood urea nitrogen levels were significantly higher before implantation in patients who died while receiving support. Renal and liver function returned to normal before transplantation. We conclude that support with the HeartMate device improved hemodynamic and subsystem function before transplantation. Long-term support with the HeartMate device has a low risk of thromboemboli and makes a clinical trial of a portable HeartMate device a realistic alternative to medical therapy. PMID- 7877302 TI - Results of extracorporeal membrane oxygenation in neonates with sepsis. The Extracorporeal Life Support Organization experience. AB - Use of extracorporeal membrane oxygenation for treatment of respiratory failure caused by sepsis is controversial because of concerns over survival benefit and hemorrhage-related complications. To evaluate the impact of the primary diagnosis of sepsis on outcome, we reviewed data from 6853 neonates in the Extracorporeal Life Support Organization Registry and defined two groups: group 1 (n = 1060), all patients undergoing extracorporeal membrane oxygenation with a primary diagnosis of sepsis; group 2 (n = 5793), those with any other primary diagnosis. A multivariate logistic regression analysis that considered 15 variables present before extracorporeal membrane oxygenation (including age, sex, birth weight, prior cardiopulmonary arrest, arterial blood gas results, and ventilator settings) was used to compare outcomes between groups. Survival was not different between the two groups (77%, group 1; 82%, group 2; p = 0.2480), although lung recovery was less frequent in the patients with sepsis (p = 0.0185). Group 1 had a higher incidence of complications including seizures (odds ratio 1.446, p = 0.0346), cerebral infarct or hemorrhage (2.310, p = 0.0001), need for dialysis (1.478, p = 0.0131), hypernatremia (2.089, p = 0.0019), hyperbilirubinemia (2.423, p = 0.0001), and dobutamine use (1.918, p = 0.0001). Neonates with sepsis are more likely to have neurologic, renal, and metabolic complications from extracorporeal membrane oxygenation but may still achieve a survival benefit equivalent to those without sepsis. From these data, extracorporeal membrane oxygenation should not be withheld from neonates solely on the basis of sepsis. Rather, management strategies should focus on limiting the incidence or severity of the common complications. PMID- 7877303 TI - A computerized control system for cardiopulmonary bypass. AB - A pump control system using a microcomputer for cardiopulmonary bypass has been developed. The parameters monitored by the computer are central venous pressure, aortic pressure, blood volume in a reservoir, and collapsing of a small vinyl bag in a venous withdrawal tube. Both pumps in the arterial infusion and the venous withdrawal lines are automatically controlled through an interface unit throughout cardiopulmonary bypass. The system regulates central venous pressure with a proportional-integral control algorithm to maintain intravascular volume constant. A screening algorithm is devised to remove artifacts introduced to the pressure measurement. During the weaning period, a perfusionist can select either the central venous pressure control or a reservoir blood volume control. Computerized pump perfusion was applied on 15 children during cardiac operations. Perfusion flow and central venous pressure were controlled satisfactorily with stable operation. Compared with conventional manually controlled pump perfusion, no significant difference was noted in mean aortic pressure, central venous pressure, net fluid balance, total urination, blood chemistry, and urinalysis. This system is useful and is expected to improve the safety of pump perfusion. PMID- 7877304 TI - Risk factors of incomplete distribution of cardioplegic solution during coronary artery grafting. AB - Myocardial distribution of cardioplegic solution infused by combined antegrade/retrograde routes was assessed with myocardial contrast echocardiography in 18 patients with chronic stable angina and three-vessel disease undergoing elective coronary artery bypass grafting. Overall myocardial opacification was significantly greater in retrograde than in antegrade cardioplegia (77.7% +/- 13.4% versus 59.1% +/- 15.7%; p = 0.0009). The difference was affected by collateral circulation, as pointed out by the significant interaction between coronary collateral circulation and percent of myocardial opacification after antegrade and retrograde cardioplegia (p = 0.002). When we performed multiple comparisons, in patients with good collaterals the opacification difference between antegrade and retrograde cardioplegia was not statistically significant (66.4% +/- 10.2% versus 76.0% +/- 15.2%; p = not significant), whereas in patients with poor collaterals myocardial opacification during retrograde cardioplegia was significantly greater (44.3% +/- 15.0% versus 81.2% +/- 9.0%; p < 0.02). During antegrade cardioplegia, patients with poor collaterals showed a lower degree of myocardial opacification than patients with good collaterals (44.3% +/- 15.0% versus 66.4% +/- 10.2%; p < 0.01). Our results show that retrograde cardioplegia in patients undergoing elective coronary artery bypass grafting offers no advantage over antegrade cardioplegia when collateral circulation is well developed. On the other hand, conventional aortic root infusion may not provide adequate myocardial protection in the subset of patients with significantly narrowed or occluded coronary arteries and poor collaterals. PMID- 7877305 TI - Acadesine inhibits neutrophil CD11b up-regulation in vitro and during in vivo cardiopulmonary bypass. AB - Granulocyte adhesion to ischemic tissue, mediated in large part by beta 2 integrin receptors, is important in the pathophysiology of reperfusion injury. Acadesine, a drug that modulates adenosine levels in ischemic tissue, has been shown to reduce reperfusion injury in animal models of ischemia. The purpose of this study was to measure changes in granulocyte CD11b/CD18 in an in vitro assay and in an in vivo trial of acadesine administered during cardiopulmonary bypass to determine whether this agent might modulate up-regulation of this adhesion receptor. In vitro, whole blood was incubated with acadesine or control diluent, stimulated with N-formyl-methionyl-leucyl-phenylalanine, and granulocyte CD11b measured. Acadesine significantly (p < 0.01) inhibited N-formyl-methionyl-leucyl phenylalanine-induced granulocyte CD11b up-regulation by a mean of 61%. In similar experiments, adenosine also inhibited N-formyl-methionyl-leucyl phenylalanine-induced granulocyte CD11b up-regulation (p < 0.01). In vivo, 34 patients at our institution participating in a multicenter trial of acadesine during cardiopulmonary bypass were randomized to placebo, low-dose, or high-dose acadesine infusion perioperatively. Combining low- and high-dose treatment groups, there was significant (p = 0.05) inhibition of granulocyte CD11b up regulation in patients receiving acadesine; granulocyte CD11b expression in the acadesine group peaked at 2.8 times baseline versus 4.3 for placebo. By contrast, monocyte CD11b up-regulation (peaking after cardiopulmonary bypass at 3 times baseline) was not affected by acadesine. Acadesine and adenosine inhibit up regulation of granulocyte CD11b in vitro, and acadesine is capable of a similar inhibition during in vivo cardiopulmonary bypass. This inhibition may contribute to the ability of these agents to decrease in vivo reperfusion injury. PMID- 7877306 TI - Triiodothyronine improves left ventricular function without oxygen wasting effects after global hypothermic ischemia. AB - Cardiopulmonary bypass results in a "euthyroid sick" state. Recently, interest has focused on the relationship between low serum triiodothyronine levels and postoperative cardiovascular hemodynamics. The present study was undertaken to more clearly define the acute effects of triiodothyronine on myocardial mechanics and energetics after hypothermic global ischemia using an ex-vivo canine heart preparation to model the clinical condition. Experiments were performed on isolated hearts subjected to hyperkalemic arrest with 90 minutes of hypothermic (10 degrees C) ischemia. Isolated hearts were cross-perfused by euthyroid support dogs in which triiodothyronine levels spontaneously decreased by 65% to 75% (p < 0.01) after the initiation of cross-perfusion. In nine heart preparations, triiodothyronine (Triostat) was given as a bolus dose (0.2 micrograms/kg) after 1 hour of baseline data collection with a subsequent measurable rise in serum triiodothyronine levels (p < 0.01). In six postischemic hearts, reverse triiodothyronine was given as a 0.2 micrograms/kg bolus. Triiodothyronine was also administered to a group of eight nonischemic, continuously perfused isolated hearts. Intrinsic myocardial contractility was assessed by analysis of the preload recruitable stroke work area, energetic efficiency from the myocardial oxygen consumption-pressure-volume area relationship, and coronary vascular resistance from analysis of coronary flow and perfusion pressure. Acute administration of triiodothyronine to postischemic hearts improved the preload recruitable stroke work area from 9.5 +/- 1.42 to 14.9 +/- 2.03 x 10(7) erg/ml, a 56% increase from baseline (p < 0.001), but had no effect on the preload recruitable stroke work area of the nonischemic hearts. The inotropic response resulting from triiodothyronine treatment did not alter the myocardial oxygen consumption-pressure-volume area relationship. Triiodothyronine treatment was associated with significantly decreased coronary resistance and increased coronary flow through a range of diastolic loading conditions in the postischemic hearts. The biologically inactive thyroid hormone metabolite reverse triiodothyronine was without effect on any of the measured parameters. On the basis of these results, we conclude that the low triiodothyronine state of cardiopulmonary bypass can be reproduced in this isolated heart model and that acute triiodothyronine treatment results in a unique inotropic action manifest only in the postischemic reperfused myocardium and is accomplished without oxygen wasting effects. PMID- 7877307 TI - Coronary flow reserve after ischemia and reperfusion of the isolated heart. Divergent results with crystalloid versus blood perfusion. AB - Mechanical function and coronary hemodynamics were assessed in 73 isolated rabbit hearts randomly subjected to 0, 10, 20, 30, or 45 minutes of 37 degrees C global ischemia and 45 minutes of reperfusion in either a modified Krebs buffer or homologous blood-perfused Langendorff mode (n = 7 to 9 hearts per group). Isovolumic developed pressure, resting coronary flow, and response to endothelium dependent (bradykinin) and -independent (nitroglycerin) agonists were quantitated at defined preload and heart rate. Perfusate did not influence systolic performance, which was impaired after 30 minutes of ischemia and fell to 64% to 72% of preischemic values after 45 minutes of ischemia (p < 0.05). However, basal coronary flow was at least sixfold greater in crystalloid-perfused hearts. Moreover, coronary hyperemia (p < 0.05) persisted for Krebs-perfused hearts subjected to all but the longest ischemic interval. After equilibration, all postischemic blood-perfused hearts had basal flow unchanged from before ischemia. Bradykinin and nitroglycerin induced similar increases in coronary flow for each group before and after each ischemia interval. However, the magnitude of this increase was greater in blood-perfused hearts (p < 0.01) and was not attenuated by the ischemic times encompassed in this protocol. In contrast, endothelium dependent and -independent coronary flow reserve was abolished after 20 minutes of ischemia or longer in Krebs-perfused hearts. These data suggest that the unphysiologic resting flow patterns of crystalloid-perfused isolated hearts obfuscate interpretation of the interaction between coronary flow reserve and ischemic injury. PMID- 7877308 TI - Results of cancer and leukemia group B protocol 8935. A multiinstitutional phase II trimodality trial for stage IIIA (N2) non-small-cell lung cancer. Cancer and Leukemia Group B Thoracic Surgery Group. AB - From October 1989 to February 1992, 74 patients with mediastinoscopically staged IIIA (N2) non-small-cell lung cancer from 30 CALGB-affiliated hospitals received two cycles of preresectional cisplatin and vinblastine chemotherapy. Patients with responsive or stable disease underwent standardized surgical resection and radical lymphadenectomy. Patients who underwent resection received sequential adjuvant therapy with two cycles of cisplatin and vinblastine, followed by thoracic irradiation (54 Gy after complete resection and 59.4 Gy after incomplete resection or no resection at 1.8 Gy per fraction). There were no radiographic complete responses to the neoadjuvant chemotherapy, although 65 (88%) patients had either a response or no disease progression. During induction chemotherapy, disease progressed in seven patients (9%). Sixty-three patients (86%) had exploratory thoracotomy, and 46 of those (75%) had resectable lesions. A complete surgical resection was accomplished in 23 patients, and 23 patients had an incomplete resection with either a diseased margin or diseased highest node resected. Operative mortality was 3.2% (2/63). In 10 patients (22% of the 46 having resection) the disease was pathologically downstaged. There was no correlation between radiographic response to the induction chemotherapy and downstaging at surgical resection. The full protocol was completed by 33 patients (45% of original cohort). Overall survival at 3 years was 23%. Patients undergoing resection had significantly improved survival at 3 years compared with patients not having resection: 46% for complete resection (median 20.9 months), 25% for incomplete resection (median 17.8 months), and 0% for no resection (median 8.5 months). Five deaths occurred during the treatment period. A total of 18 of the 46 (39%) patients who underwent resection are either alive and disease free or have died without recurrence. PMID- 7877309 TI - Postintubation tracheal stenosis. Treatment and results. AB - A total of 503 patients underwent 521 tracheal resections and reconstructions for postintubation stenosis from 1965 through 1992. Fifty-three had had prior attempts at surgical resection, 51 others had undergone various forms of tracheal or laryngeal repair, and 45 had had laser treatment. There were 251 cuff lesions, 178 stomal lesions, 38 at both levels, and 36 of indeterminate origin. Sixty-two patients with major laryngeal injuries required complete resection of anterior cricoid cartilage and anastomosis of trachea to thyroid cartilage, and 117 had tracheal anastomosis to the cricoid. A cervical approach was used in 350, cervicomediastinal in 145, and transthoracic in 8. Length of resection was 1.0 to 7.5 cm. Forty-nine had laryngeal release to reduce anastomotic tension. A total of 471 patients (93.7%) had good (87.5%) or satisfactory (6.2%) results. Eighteen of 37 whose operation failed underwent a second reconstruction. Eighteen required postoperative tracheostomy or T-tube insertion for extensive or multilevel disease. Twelve died (2.4%). The most common complication, suture line granulations (9.7%), has almost vanished with the use of absorbable sutures. Wound infection occurred in 15 (3%) and glottic dysfunction in 11 (2.2%). Five had postoperative innominate artery hemorrhage. Resection and reconstruction offer optimal treatment for postintubation tracheal stenosis. PMID- 7877310 TI - Pathologic comparison of video-assisted thoracic surgical lung biopsy with traditional open lung biopsy. AB - Video-assisted thoracic surgical lung biopsy is an alternative to traditional open lung biopsy for diagnosis in patients with pleuropulmonary diseases. Between January 7, 1991, and August 3, 1993, 71 consecutive patients had video-assisted thoracic surgical lung biopsy and 42 patients had traditional open lung biopsy. A specific histologic diagnosis that correlated with the clinical findings was sought in each case and the yield was compared between the two groups. Procedure related artifactual changes were also evaluated; the extent of traumatic hemorrhage and neutrophil margination as a result of tissue manipulation was significantly greater for patients in the video-assisted thoracic surgical lung biopsy group than for those in the open lung biopsy group, but the changes were generally minor and did not affect diagnostic yield. Complications developed in 11 (15%) of 71 patients in the video-assisted thoracic surgical lung biopsy group including 5 patients with prolonged air leakage (more than 10 days); 2 with pneumonia; and 1 each with bleeding, late pneumothorax necessitating readmission, mucus plug necessitating bronchoscopy, and a hypoxic episode necessitating mechanical ventilation. On the other hand, 7 (17%) of 42 patients in the open lung biopsy group had complications including 4 patients with prolonged air leakage (more than 10 days) and 3 with pneumonia. There were 6 (8%) operative deaths in patients who had video-assisted thoracic surgical lung biopsy and 7 (17%) in the open lung biopsy group; all had preoperative respiratory failure. We conclude that video-assisted thoracic surgical lung biopsy is an acceptable alternative to open lung biopsy for diagnosis of pulmonary infiltrates or indeterminate nodules. PMID- 7877311 TI - Video-assisted thoracoscopic surgery for congenital heart disease. AB - Video-assisted endoscopic techniques have reduced operative trauma in adult thoracic and general surgery, but applications in children with congenital heart disease have been limited. We report the development of video-assisted thoracic surgery procedures for neonates and infants with cardiovascular disease. Endoscopic instruments and techniques for pediatric cardiovascular procedures were designed and tested in the animal laboratory. Forty-eight operations were subsequently performed in 46 pediatric patients ranging in age from 2 hours to 14 years (median 9 months), weighing from 575 grams to 54 kg (median 8.5 kg). Clinical applications included seven different surgical procedures: patent ductus arteriosus interruption in infants (n = 26) and premature neonates (n = 5), vascular ring division (n = 8), pericardial drainage and resection (n = 3), arterial and venous collateral interruption (n = 2), thoracic duct ligation (n = 2), epicardial pacemaker lead insertion (n = 1), and diagnostic thoracoscopy (n = 1). There was no operative mortality. Technical success, defined as a video assisted procedure completed without incising chest wall muscle or spreading the ribs, was achieved in 39 of 48 procedures (82%), with thoracotomy required to complete nine procedures. Most patients (22/25, 88%) undergoing elective ductus ligation were extubated in the operating room and discharged from the hospital within 48 hours of the operation. Eight of the last 10 patients having ductus ligation were discharged on the first postoperative day. Residual ductal flow was assessed by (1) transesophageal echocardiography in the operating room (incidence: 0/25, 0%, 70% CL 0% to 7.3%); (2) discharge auscultation (incidence: 1/30, 3%, 70% CL 0.5% to 10.8%); and (3) follow-up Doppler echocardiography (incidence: 3/25, 12%, 70% CL 5.4% to 22.6%). Video-assisted thoracoscopic techniques can be safely applied to pediatric patients with patent ductus arteriosus and vascular rings and may become an effective addition to the staged management of more complex forms of congenital heart disease. PMID- 7877312 TI - Outcome of pulmonary and aortic homografts for right ventricular outflow tract reconstruction. AB - To determine late patient outcome and homograft durability, we reviewed 326 patients who received aortic (n = 230) or pulmonary (n = 118) cryopreserved homografts for right ventricular outflow reconstruction between January 1985 and October 1993. Patient survival, including operative mortality, 5 years after the operation was similar between the two groups (pulmonary homograft 86%, aortic homograft 80%; p = not significant by log-rank test). However, 5-year freedom from homograft failure was significantly better for pulmonary homografts (94% versus 70%, p < 0.01 by log-rank test). Late calcification was evaluated by chest roentgenography and echocardiography. Overall, 20% of aortic homografts became moderately or severely calcified compared with 4% of pulmonary homografts (p < 0.01). Twenty-six percent of aortic homografts in children 4 years old or younger had moderate or severe obstruction associated with calcification, whereas only 11% of aortic homografts in patients over 4 years of age had calcific obstruction (p < 0.01). No late deaths among patients receiving pulmonary homografts were related to graft failure; two late deaths in the aortic homograft group were homograft related. Risk factors for patient mortality and homograft failure (defined as either need for homograft replacement because of homograft failure or as homograft-related death) were identified by the Cox multivariate analysis. Aortic type of homograft was a significant risk factor for homograft failure (p < 0.0001), but type of homograft was not correlated with patient mortality. Age 4 years or younger was a significant risk factor for both mortality (p < 0.01) and homograft failure (p = 0.03) in aortic homograft recipients but not in pulmonary homograft recipients. These results indicate that both aortic and pulmonary homografts provided excellent intermediate-term patient survival after right ventricular outflow tract reconstruction, but pulmonary homografts are more durable than aortic homografts with less calcification and obstruction, especially among children 4 years old or younger. PMID- 7877313 TI - Aortic implantation of anomalous left coronary artery. An improved surgical approach. AB - Anomalous origin of the left coronary artery from the pulmonary artery may present a technical challenge. Direct implantation of the anomalous left coronary artery into the aorta to provide a two coronary artery system is the preferred surgical approach. We describe a modification of this technique to allow anastomosis of the anomalous left coronary artery with the excised button of pulmonary artery from within the lumen of the aorta. We have used this procedure in six children and one adult with anomalous left coronary artery with favorable outcome. The potential benefits of this modified technique are (1) improved operative exposure, (2) ability to implant the anomalous left coronary artery in the appropriate sinus, (3) avoidance of aortic valve damage or distortion because of improved exposure, and (4) applicability to patients of all ages. PMID- 7877314 TI - Bleeding and use of blood products after heart operations in infants. AB - Recent studies have suggested that postoperative bleeding is decreased in pediatric heart operations if fresh whole blood instead of blood component therapy is used for postoperative transfusions. Because this is in contrast to our practice to use whole blood for only the priming of the cardiopulmonary bypass circuit and then to use blood components for additional transfusion requirements, it was our interest to analyze the bleeding complications and the use of blood products after heart operations in infants. The patient records of the 73 infants operated on in 1992 were reviewed. The chest tube drainage varied from 3 to 51 ml/kg per 6 hours (mean 10 ml/kg) and it did not correlate with any of the tested clinical or laboratory parameters. One infant underwent reoperation because of surgical bleeding. Disseminated intravascular coagulation developed in another patient. Sixty-eight patients (93%) needed red blood cell supplementation. Sixty-eight percent of patients between 1 month and 1 year old could be treated without any other postoperative transfusion except for red blood cell supplementation. In contrast, in the neonates, platelet concentrates or fresh frozen plasma, or both, were used in 61% of the patients. In addition to the known immaturity of the hemostatic system, the increased need for platelet concentrates in the neonates was attributed to longer cardiopulmonary bypass time, deeper hypothermia in association with circulatory arrest, larger dosages of heparin, and more extensive plasma dilution during cardiopulmonary bypass. In conclusion, a low rate of bleeding complications and acceptably low general blood loss can be achieved postoperatively with blood component therapy. PMID- 7877315 TI - Biventricular repair in cardiac isomerism. Report of seventeen cases. AB - Ninety-three patients with cardiac isomerism were treated surgically from July 1985 to June 1991. Among them, three patients with right and 14 with left isomerism underwent biventricular repair. Ages ranged from 4 months to 41 years (mean 4.8 years). Anatomic repair was accomplished in 15 patients and functional repair with the right ventricle used as the systemic ventricle in two patients. Methods of atrial septation to separate pulmonary venous flow from systemic venous flow included atrial partition with a straight patch in seven patients, intraatrial rerouting with a tailored baffle in five, and a Mustard-type atrial switch in five. One hospital death (5.8%) and two late deaths (12%) occurred. Two patients required reoperation (12%), one reconstruction of a stenotic systemic venous connection and one mitral valve replacement because of incompetence. Surgically induced complete atrioventricular block was not observed in any of the patients. Optimal atrial septation offers the possibility of biventricular repair for patients with acceptable intraventricular structure. PMID- 7877316 TI - Aortic root replacement. Risk factor analysis of a seventeen-year experience with 270 patients. AB - Between September 1976 and September 1993, 270 patients underwent aortic root replacement at our institution. Two hundred fifty-two patients underwent a Bentall composite graft repair and 18 patients received a cryopreserved homograft aortic root. One hundred eighty-seven patients had a Marfan aneurysm of the ascending aorta (41 with dissection) and 53 patients had an aneurysm resulting from nonspecific medial degeneration (17 with dissection). These 240 patients were considered to have annuloaortic ectasia. Thirty patients were operated on for miscellaneous lesions of the aortic root. Thirty-day mortality for the overall series of 270 patients was 4.8% (13/270). There was no 30-day mortality among 182 patients undergoing elective root replacement for annuloaortic ectasia without dissection. Thirty-six of the 270 patients having root replacement also had mitral valve operations. There was no hospital mortality for aortic root replacement in these 36 patients, but there were seven late deaths. Twenty-two patients received a cryopreserved homograft aortic root; 18 of these were primary root replacements and four were repeat root replacements for late endocarditis. One early death and two late deaths occurred in this group. Actuarial survival for the overall group of 270 patients was 73% at 10 years. In a multivariate analysis, only poor New Year Heart Association class (III and IV), non-Marfan status, preoperative dissection, and male gender emerged as significant predictors of early or late death. Endocarditis was the most common late complication (14 of 256 hospital survivors) and was optimally treated by root replacement with a cryopreserved aortic homograft. Late problems with the part of the aorta not operated on occur with moderate frequency; careful follow-up of the distal aorta is critical to long-term survival. PMID- 7877317 TI - Subxiphoid pericardial drainage for pericardial tamponade. AB - As a result of recent reports and enthusiasm for video-assisted thorascopic pericardiectomy, we reviewed our experience with subxiphoid pericardial drainage. From August 15, 1988, to June 7, 1993, 155 patients underwent subxiphoid pericardial drainage for pericardial effusion associated with pericardial tamponade. The group comprised 85 female (55%) and 70 male patients whose ages ranged from 5 weeks to 88 years. The procedure was carried out with general anesthesia in 113 patients (72%) and with local anesthesia and sedation in 42 patients. Underlying cancer was present in 82 patients; 73 patients had benign disease. Follow-up is complete in all patients. The overall 30-day mortality was 20%; in patients with cancer it was 32.9% (27/82) versus 5.4% (4/73) for patients with benign disease. No postoperative death was attributed to the surgical procedure. Recurrent pericardial tamponade necessitating further surgical intervention occurred in four patients (2.5%), two with cancer (2.4%) and two with benign disease (2.7%). Median survival after subxiphoid pericardial drainage in patients with benign disease was more than 800 days versus 83 days in patients with cancer (p < 0.01). Median survival after pericardial drainage in patients with cancer who had malignant pericardial effusion was 56 days compared with 105 days for patients with cancer who did not have tumor in the pericardium (p < 0.05). We believe that subxiphoid drainage is the procedure of choice for patients with pericardial tamponade. It is accomplished quickly, is associated with minimal morbidity, and prevents recurrent tamponade in 97.4% (151/155) of patients. PMID- 7877318 TI - Coronary artery bypass grafting with the inferior epigastric artery. Midterm clinical and angiographic results. AB - Between December 1988 and September 1993, 157 patients (141 men, 16 women, average age 60.2 years, range 37 to 78 years) underwent a complete myocardial revascularization with 157 inferior epigastric artery grafts and 285 internal mammary artery grafts (281 in situ, 4 free grafts). A total of 543 distal arterial anastomoses (average 3.4, range two to five per patient) were constructed, 376 with the internal mammary artery and 167 with the inferior epigastric artery. The inferior epigastric artery grafts were anastomosed to two left anterior descending, 5 diagonal, 34 circumflex, and 126 right coronary arteries. The indications for the use of the inferior epigastric artery were the unavailability of conventional conduits in 56 patients and a favorable anatomy or a young age in 101 selected patients. The clinical follow-up averages 31.8 months (range 6 to 62 months). Four patients died early, and there were three perioperative nonfatal myocardial infarctions. Eight patients required early reoperation for thoracic bleeding (2) or drainage of an abdominal parietal collection (6). There were four late deaths (2 sudden deaths, 2 noncardiac causes) and one nonfatal myocardial infarction. Angina recurred in nine patients, of whom one required reoperation and three underwent successful percutaneous balloon angioplasty of a native coronary artery (2) or an old saphenous vein graft (1). An early recatheterization was obtained before discharge (average 11 days) in 135 patients: 132 of 135 inferior epigastric artery grafts were patent. Seventy-seven patients underwent a second angiographic restudy 6 to 43 months after the operation. Forty-four of the 48 inferior epigastric artery grafts restudied within the first postoperative year (average 8.5 months) were patent, but eight showed a diffuse narrowing. Twenty-eight of the 29 inferior epigastric artery grafts examined angiographically between 13 and 43 months (average 25 months) were open, and among those 29, 25 were widely patent, perfectly matching the receiving coronary artery. Most of the occluded or narrowed inferior epigastric artery grafts were grafted onto coronary arteries with mild stenosis at restudy. Five patients underwent a third angiographic reexamination up to 60 months after the operation (average 39 months). All five inferior epigastric artery grafts were widely patent. The early attrition rate of the inferior epigastric artery, as for any free arterial graft, is probably the result of both the loss of a true pedicle and the need for constructing an additional proximal anastomosis. The fact that the patency rate of the inferior epigastric artery graft seems to remain stable beyond 1 year could suggest a good durability in the future. PMID- 7877319 TI - Effect of vancomycin infusion on cardiac function in patients scheduled for cardiac operation. AB - Patients scheduled for cardiac operation often receive vancomycin before the operation to decrease postoperative staphylococcal wound infections. In animal studies, vancomycin depressed cardiac function approximately 15%. Because of the potentially serious consequences of myocardial depression in patients undergoing cardiac operation, we examined the effect of vancomycin infusion on cardiac hemodynamics in patients scheduled for cardiac operation. Patients who were scheduled for cardiac operation and vancomycin prophylaxis were enrolled in our study. After baseline cardiac output, mean arterial pressure, central venous pressure, and pulmonary capillary wedge pressure were measured, 1 gm of vancomycin HCl was infused over 1 hour. Cardiac output, mean arterial pressure, central venous pressure, and pulmonary capillary wedge pressure were measured at 15, 30, 60, 90, and 120 minutes after the start of the infusion. In the 46 patients that completed the study, no significant change was observed in cardiac output or systemic vascular resistance at any time when compared with baseline. Mean arterial pressure increased significantly (p = 0.03) between baseline (90.8 +/- 2.4 standard error of mean) and 90 minutes (94.1 +/- 2.4 standard error of mean). One patient had a transient 30% fall in mean arterial pressure and systemic vascular resistance with facial flushing during the infusion. In conclusion, we found that vancomycin infusion over 1 hour in patients before cardiac operation is safe and not associated with cardiac depression. PMID- 7877320 TI - Implantable cardioverter-defibrillator. Evaluation of clinical neurologic outcome and electroencephalographic changes during implantation. AB - During placement of implantable cardioverter-defibrillators, ventricular arrhythmias are induced to test the function of the devices. Although cerebral hypoperfusion and ischemic electroencephalographic changes occur in patients while implantable cardioverter-defibrillators are being tested, no investigation has assessed neurologic outcome in these patients. Nine patients having either implantation or change of an implantable cardioverter-defibrillator underwent neurologic examination and neuropsychometric tests before and after the operation. After induction of general anesthesia and insertion of implantable cardioverter-defibrillator leads (when needed), ventricular fibrillation, ventricular flutter, or ventricular tachycardia, was induced by means of programmed electrical stimulation. Implantable cardioverter-defibrillator testing continued until satisfactory lead placement was confirmed. The intraoperative electroencephalographic recording was analyzed for evidence of ischemic change. In all, an electroencephalogram was recorded during 50 periods of circulatory arrest. Mean duration of the arrest periods was 13.6 seconds. By means of conventional visual inspection of the raw electroencephalogram, high-amplitude rhythmic delta or theta, voltage attenuation, or loss of fast frequency activity was observed in 30 of the arrests. By means of an automated technique of electroencephalographic interpretation based on power spectral analysis, electroencephalographic changes were correctly identified in 26 of the arrests. The incidence of these electroencephalographic changes was dependent on the arrest duration. The mean interval from arrest onset to electroencephalographic change was 7.5 seconds (standard deviation +/- 1.8 seconds). In patients with electroencephalographic changes during multiple arrests, no downward trend in this interval was detected in later arrests and no evidence of persistent ischemic change was observed in electroencephalograms recorded after the conclusion of implantable cardioverter-defibrillator testing. Postoperative neurologic and neuropsychometric testing was completed in eight patients, none of whom exhibited a new neurologic deficit, exacerbation of a preexisting neurologic condition, or significant deterioration in neuropsychometric performance. We conclude that the brief arrest of cerebral circulation induced during insertion of an implantable cardioverter-defibrillator is not associated with permanent neurologic injury. PMID- 7877323 TI - A communication between the gastroepiploic artery and vein in the pedicle. PMID- 7877322 TI - Comparison of outcomes with three atrial incisions for mitral valve operations. Right lateral, superior septal, and transseptal. AB - We compared the preoperative status, operative factors, and postoperative outcomes among patients having mitral valve operations with three atrial incisions. The incisions were right lateral (n = 66), superior septal (n = 46), and transseptal (n = 37). Differences in patient and operative factors among the groups were not predictors of adverse postoperative outcomes with multiple regression analysis. Postoperative pulmonary failure was less common in the superior septal group. Patients in the superior septal group more commonly required permanent pacemakers than those in the right lateral group. In patients with sinus rhythm before operation, sinus rhythm had returned before hospital discharge more commonly in those in the right lateral group (35 of 44, 80%) than in those in the superior septal group (18 of 28, 46%) or in the transseptal group (9 of 13, 69%). With multiple regression analysis the type of atrial incision was not a predictor of postoperative pulmonary failure or need for permanent pacemaker. Right lateral and transseptal atrial incisions were predictors of retention of sinus rhythm after operation. We conclude that the results of superior septal incision are comparable with those of other incisions except for a slightly greater risk of loss of sinus rhythm. One must weigh the technical advantages of the superior septal incision against the risk of loss of sinus rhythm. PMID- 7877321 TI - Chronic obstructive pulmonary disease in patients undergoing coronary artery bypass grafting. AB - The purpose of this study was to evaluate the effect of chronic obstructive pulmonary disease on patients undergoing coronary artery bypass grafting. Between June 1991 and June 1993, 651 patients underwent coronary artery bypass grafting: 37 patients (group I) had significant chronic obstructive pulmonary disease. These patients were compared with 37 matched control subjects (group II). Comparison of the groups was made with regard to postoperative morbidity and mortality. Quality of life of survivors was compared at the last follow-up. More patients in group I had preoperative arrhythmias (8 versus 1, p = 0.014). Group I patients had lower values of forced expiratory volume in 1 second (1.366 +/- 0.032 L versus 2.335 +/- 0.49 L, p < 0.0001), lower oxygen tension (63.5 +/- 8.2 versus 79.1 +/- 13.4 mm Hg, p = 0.001), and higher carbon dioxide tension (44.8 +/- 6.5 mm Hg versus 39.7 +/- 3.6 mm Hg, p = 0.001). After operation patients in group I had a longer hospital stay (8.1 +/- 3.6 days versus 6.6 +/- 1.7 days, p = 0.0236) and longer intensive care unit stay (2.64 +/- 0.9 days versus 1.23 +/- 0.49 days, p = 0.0001). More patients in group I required prolonged intubation (7 versus 1, p = 0.0278) and reintubation (5 versus 1, p = 0.088). More patients in group I had significant arrhythmias (27 versus 9, p < 0.0001). During a 16-month follow-up period, five patients in group I died, whereas none in group II died (p = 0.0271). Four deaths were related to arrhythmias. More group I patients were not functionally improved by the operation (17 versus 3, p = 0.0056). The results of coronary artery bypass grafting in patients with significant chronic obstructive pulmonary disease were not favorable in midterm follow-up. A major cause for morbidity and mortality was postoperative arrhythmias. PMID- 7877324 TI - Cryopreserved aortic homograft for mycotic aneurysm. PMID- 7877325 TI - Ophthalmoscopic findings demonstrate reduced cerebral blood flow during retrograde cerebral perfusion. PMID- 7877326 TI - Right ventricular rupture after mediastinitis. PMID- 7877327 TI - Myocardial rewarming during normothermic cardiopulmonary bypass. PMID- 7877328 TI - Surgical management for metachronous bronchogenic cancer occurring after pneumonectomy. PMID- 7877329 TI - Ostioplasty for isolated coronary artery ostial stenosis. PMID- 7877330 TI - Radix bupleuri added to the os draconis and concha ostreae decoction in the treatment of neuropsychopathies--a report of 4 cases. PMID- 7877331 TI - Clinical observation on the effects of combined traditional Chinese and Western medicine therapy for excessive suppressive syndrome. AB - Sixty-eight cases of sterility due to excessive suppressive syndrome were treated by differential administration of Chinese drugs combined with clomiphene citrate and progesterone. This combined therapy was found to be significantly superior in therapeutic effect to administration of Western drugs alone or administration of Chinese drugs supplemented by progesterone. Resultant pregnancy rate was 57.4%. PMID- 7877332 TI - Chai ling tang in the treatment of steroid-dependent nephrosis syndrome. PMID- 7877333 TI - Application of biao-ben differentiation in acupuncture therapy. PMID- 7877334 TI - Comparative observation on effect of electric acupuncture of neiguan (P 6) at chen time versus xu time on left ventricular function in patients with coronary heart disease. AB - Paired experimental design was adopted in this experiment for comparative observation on effect of electric acupuncture (EA) of Neiguan (P 6) at Chen Time (7 a.m. to 9 a.m.) versus Xu Time (7 p.m. to 9 p.m.) on left ventricular function in patients with coronary heart disease (CHD). The results show that EA performed at Chen Time could improve the left ventricular function of CHD patients as indicated by shortening of PEPI and decrease of PEPI/LVETI ratio; on the contrary, EA performed at Xu Time prolonged PEPI and raised PEPI/LVETI ratio in CHD patients, suggesting impairment of left ventricular function. PMID- 7877335 TI - Treatment of sciatica by acupuncture at jiaji points--a report of 168 cases. PMID- 7877336 TI - Seventy-five cases of stiff neck treated by acupuncture at acupoint yanglao (SI 6). PMID- 7877337 TI - Acupuncture treatment of headache. PMID- 7877338 TI - 25 cases of cystoparalysis following gynecological surgery treated with herbal drugs and acupuncture. PMID- 7877339 TI - Treating osteoarthritis of the knee joint by traditional Chinese medicine. PMID- 7877340 TI - Treatment of adolescent myopia by pressure plaster of semen impatientis on otoacupoints. AB - 295 cases (424 eyes) of adolescent myopia were treated by pressure plaster of Semen Impatientis on otoacupoints with a cure rate of 44.3% and a total effective rate of 98.5%. 36 random cases (69 eyes) were compared with the same number of similar control cases. Findings were that the therapeutic effects of the pressure plaster group excelled significantly those of the control group. PMID- 7877341 TI - 50 cases of dysfunctional uterine bleeding treated by puncturing the effective points--a new system of acupuncture. PMID- 7877342 TI - The effect of radix salviae miltiorrhizae composita and ligustrazine on lipid peroxidation in low density lipoprotein due to copper dichloride. AB - It is well known that lipid peroxide in low density lipoprotein (LDL) plays an important role in atherosclerosis and atherosclerotic diseases. We used oxidized LDL generated by incubating LDL from healthy persons with copper dichloride as a model to investigate the anti-lipid-peroxide property of Radix Salviae Miltiorrhizae Composita (RSMC) and ligustrazine. The changes in concentrations of lipid peroxide and lipids in LDL due to Cu++ were studied, and the effects of RSMC and ligustrazine on the changes were studied. The results in our study indicate that RSMC has a potential role on anti-lipid-peroxidation, but it was not found that ligustrazine has similar anti-peroxidation action. PMID- 7877343 TI - Effects of liuwei dihuang wan [symbol: see text:bd and some other TCM drugs on bone biomechanics and serum 25 (OH)D3 content in rats. AB - After a relatively long-term injection of hydrocortisone into rats, the strength of bone (anti-stress capacity) reduced evidently, while the rigidity (anti deformity capacity) increased markedly (ie, bone fragility elevated). At the same time, the content of serum 25(OH)D3 decreased remarkably. After oral administration of Liuwei Dihuang Wan ([see symbol: see text]), anti-stress capability of bone increased evidently and its anti-deformity capability returned to normal; however, there was no elevation of serum 25(OH)D3 content. The effect of Longmu Zhuanggu Chongji ([see symbol: see text]) or Jisheng Shenqi Wan (see symbol: see text]) was lower than that of Liuwei Dihuang Wan. The experiments suggests that Liuwei Dihuang Wan is beneficial to preventing and curing osteoporosis, but no correlation between its mechanism and the metabolism of 25(OH)D3 was demonstrated. PMID- 7877344 TI - Comparative observations on the types of atrophic gastritis and biopsy pathology of gastric mucosa. AB - 300 cases of chronic atrophic gastritis were classified into 3 types of qi deficiency of spleen and stomach, yang-deficiency of spleen and stomach, and yin deficiency of spleen and stomach according to syndrome differentiation of traditional Chinese medicine. The biopsy specimens of gastric mucosa were examined histopathologically and for the presence of pyloric spirobacteria. The results showed that the type of yin-deficiency was the most serious in the degree of pathologic changes, or the glandular atrophy and the interstitial inflammatory cellular infiltration, while the rate of pyloric spirobacteria presence was comparable in all types. PMID- 7877345 TI - Studies on reducing and reinforcing manipulation of acupuncture during the past 4 years (continued). PMID- 7877346 TI - [Study of cerebral activity with functional magnetic resonance]. AB - BACKGROUND: Functional magnetic resonance is a new imaging method which allows the incruent observation of human cerebral activity. The authors describe their method of functional magnetic resonance and the results of cerebral activation. METHODS: A total of 364 functional sequences were performed in 52 volunteers with a magnetic resonance system of 1.5 Tesla. A gradient echo sequence with a long echo time sensitive to the changes in oxygenation of venous blood was used. Different cortical areas were stimulated by visual, motor and language maneuvers and by complex mental operations. RESULTS: Different cerebral areas representative of different levels of cerebral functional complexity were consistently activated and reproduced. Experiments of activation of primary cerebral cortex (visual and motor), premotor regions, specific area of language and areas of cortical association for cognitive operations are described. CONCLUSIONS: Functional magnetic resonance imaging is a sensitive method for the observation of cerebral activity and provides functional images with great spatial and temporal resolution. This may be useful in both clinical and basic investigation. PMID- 7877347 TI - [Recurrence of Graves-Basedow disease: the influence of treatment schedule]. AB - BACKGROUND: The aim of the present study was to evaluate the possible influence of 2 different methods of treatment (antithyroid drugs and antithyroid drugs plus levothyroxine) on the number of recurrences in Graves' disease, as well as to study the possible prognostic factors for the evolution of the disease. METHODS: Seventy-six patients allocated in to 2 treatment groups were studied. Group A included those patients treated with decreasing doses of carbimazole and group B included patients treated with high doses of carbimazole plus levothyroxine. The follow-up of these patients was carried out over a minimum of 36 months after discontinuation of treatment. RESULTS: No significant differences were observed in either the clinical characteristics or hormonal or antibody values in both groups on initiation and at the end of treatment. The percentage of recurrence in group A patients during the first 12 months of follow-up was significantly greater (65% vs 23%, p < 0.001) than in group B. The percentage of recurrence equalled (62.8% vs 60.7%, p = NS) on prolongation of follow-up of up to 36 months. Recurrence was not correlated with either the clinical or biochemical parameters evaluated, although it did correlate with goiter size with recurrence observed in 100% of the patients with goiter greater than or equal to II. CONCLUSION: The association of levothyroxine to treatment with carbimazole in Graves' disease delays the appearance of recurrence but does not significantly decrease it in comparison with the treatment with carbimazole in decreasing doses. Only the size of goiter on initiation of treatment may be a prognostic factor for disease evolution. PMID- 7877349 TI - [What can we eat today in order not to get ill tomorrow?]. PMID- 7877348 TI - [Medicina Clinical: towards its definitive international recognition]. PMID- 7877350 TI - [Parvovirus B19]. PMID- 7877352 TI - [Medical-clinical audit (III). Facets]. PMID- 7877351 TI - [Arthropathy associated with infection by parvovirus B19. Description of 4 cases]. AB - Four cases of human parvovirus infection in which the main clinical manifestation was a polyarthritis are described. Four females with ages ranging from 30 to 32 years presented with acute symmetrical polyarthralgias involving hands and knees. In addition, evidence of synovitis in the ankles and tenosynovitis of the fingers was found in two and three cases respectively. Half of the patients noticed an erythematous rash in the preceding days. Laboratory studies were normal in all cases. Antinuclear antibodies and rheumatoid factor were not detected in any case. All patients had significant levels of IgG and IgM antibodies to parvovirus B19 at the time of presentation and a rise in IgG and a fall in IgM levels were seen at two months. All cases cleared up within two weeks without treatment. PMID- 7877353 TI - [Tumor necrosis factor and AIDS]. PMID- 7877354 TI - [Clinical and analytical manifestations of the primary antiphospholipid syndrome]. PMID- 7877355 TI - [The seroprevalence of antibodies against Lyme borreliosis in a healthy population on the Island of Lanzarote, Spain]. PMID- 7877356 TI - [Ambulatory arterial blood pressure in normotensive children]. AB - BACKGROUND: The aim of the present study was to obtain out patient blood pressure values in normotensive children based on age, height, and sex in order to determine reference values. METHODS: Out patient blood pressure monitorization was performed in 248 healthy normotensive children (129 males and 119 females, ages 6 to 16 years) (casual blood pressure < P95 specific for age and sex) over 24 hours by the Spacelabs 90207 oscilometric monitor on a normal schoolday. An appropriately sized armband was chosen for each case with the readings being programmed every 20 minutes between 6:00 a.m. and midnight and every 30 minutes for the remaining readings. The means of 24 hour blood pressure (all the readings obtained), day period (8 to 22 hours) and night period (midnight to 6:00 a.m.) and the circadian variability (difference and the ratio between the mean values of day and night) were calculated. The children were divided into subgroups according to sex, age (6-9, 10-12 and 13-16 years) and height (1.09-1.37; 1.38 1.51, and 1.52-1.75 meters). Monitorizations with a percentage of erroneous readings over 30% were excluded from the study. RESULTS: Only 7 children were excluded due to a high percentage of erroneous readings. The mean of the valid readings made in the remaining 241 cases was 62 +/- 7. A significant increase was observed in the values of out patients systolic blood pressure with age and height. The same was not seen in diastolic blood pressure. Nocturnal blood pressures were lower to the diurnal pressures (11% systolic, 22% diastolic). P95 was considered as the upper limit of normality for the means of each of the periods of systolic and diastolic blood pressure in each subgroup of sex, age and height. CONCLUSIONS: The blood pressure values obtained from a population of normotensive children may be useful to understand the behaviour of out patient blood pressure in children and establish the limit for defining high blood pressure. PMID- 7877357 TI - [How Miguel Choque died]. PMID- 7877358 TI - [Medico-clinical audit (and IV). Perspectives]. PMID- 7877359 TI - [Development of coronary arteriosclerosis and its clinical complications]. PMID- 7877360 TI - [Inguinal hernia and antibiotic prophylaxis]. PMID- 7877361 TI - [Ambulatory study of patients with pleural tuberculosis]. PMID- 7877362 TI - [Tetraplegia caused by intramedullary hemorrhage and chronic hepatopathy]. PMID- 7877363 TI - [Prevalence of diabetes mellitus among Spanish youngsters estimated based on military service exemptions]. PMID- 7877364 TI - [Posterior uveitis associated with acute tubulointerstitial nephritis with favorable response to cyclosporine. Pathogenic implications]. PMID- 7877365 TI - [Thrombocytopenia associated to human immunodeficiency virus infection]. PMID- 7877366 TI - [Early diagnosis of prostatic cancer: current status]. PMID- 7877367 TI - [Thrombocytopenia associated with human immunodeficiency virus infection]. PMID- 7877369 TI - [Resistant tuberculosis in a prison population during 1991-1993]. AB - BACKGROUND: To know the prevalence of resistant tuberculosis and the characteristics of the same in the penitentiary medium in the Madrid area (Spain). METHODS: From March 1, 1991 to August 31, 1993 a prospective study was carried out in patients with isolations of Mycobacterium tuberculosis resistant to some of the common antituberculous drugs within the context of tuberculosis in a penitentiary population attended in the Hospital General Penitenciario (Madrid). Demographic, clinical, analytical, and microbiological data were collected as was that on the antituberculous treatment used. The study of sensitivities was performed by the proportions method. RESULTS: Tuberculosis was diagnosed in 275 patients according to strict microbiological criteria (positive Lowenstein culture). The antibiogram was performed in 218 isolations. Twenty strains resistant to some first line antituberculous drug (9%) (confidence interval [CI] p < 0.05:6-14), 9 of which were found to be multiresistant, were detected in 20 patients. Out of the patients in whom the sensitivity of the isolate was known, 173 had not previously undergone antituberculous treatment. Six of these patients were found to be resistant to isoniazide (3.5%) (CI p < 0.05:1.4-7.7) and 2 patients were resistant to rifampicin (1.2%) (CI p < 0.5:0.2 4.5). The other 45 patients had previously undergone antituberculous drugs with 8 isolates presenting resistance to isoniazide and 11 to rifampicin. Eighty-four percent of the patients with resistant tuberculosis and 90% of the sensitive cases were coinfected with HIV infection with the differences not being statistically significant. The HIV positive patients with resistant tuberculosis showed a mean CD4 positive lymphocytes of 0.76 x 10(9)/l (CI p < 0.5:0.028-0.213) and those with sensitive tuberculosis had 0.165 x 10(9)/l (CI p < 0.05:0.133 0.196) (p < 0.01). CONCLUSIONS: Tuberculosis resistant to common antituberculous drugs was detected in a Spanish penitentiary population. The level of the resistance of the isolations of Mycobacterium tuberculosis should be monitored both inside and outside of the penitentiary medium in an attempt to avoid the progression of resistant tuberculosis within the Community. PMID- 7877368 TI - [Tuberculosis in La Rioja from 1988 to 1993. Clinical course, localization, influence of human immunodeficiency virus infection, and sensitivity of mycobacterial tests]. AB - BACKGROUND: The present study was performed to analyze the evolution of the incidence of tuberculosis in La Rioja (Spain) from January 1988 to March 1993. The influence of factors such as HIV infection and alcoholism was analyzed. The sensitivity of the bacilloscopy in the diagnosis was studied. METHODS: The cases were collected from the Regional Tuberculosis Program of the Public Health Department in La Rioja, with clinical histories being collected from the Internal Medicine Department of the Hospital San Millan in Logrono. Cases of tuberculosis were microbiologically confirmed by cultures of Mycobacterium tuberculosis. RESULTS: The total number of cases studied was 649 with the incidence of tuberculosis in La Rioja being 51 cases/100,000 inhabitants in 1992. The mean age of all the patients was 45 years with 80% of the tuberculosis being pulmonary and 20% extrapulmonary. Twelve percent of the patients were HIV+; 18% being extrapulmonary tuberculosis and 10.8% pulmonary tuberculosis, p < 0.02. Pleural and urogenital tuberculosis were present in fewer HIV+ patients. Bacilloscopy was negative requiring a culture for diagnosis in 28.6% of the cases with this circumstance more frequently occurring in the pleural and urogenital forms of the diseases. Treatment has evolved from the use of ethambutol in the first few years to the present use of pyrazinamide. CONCLUSIONS: No trend towards an increase in the incidence of tuberculosis in the time period studied was observed in La Rioja. Extrapulmonary tuberculosis was the type of tuberculosis most frequently found in HIV positive patients, with pleural and urogenital forms of the disease being less frequently found in these patients. In these case the bacilloscopy was also found to be negative more frequently. PMID- 7877371 TI - [Euthanasia. The right to die with dignity]. PMID- 7877370 TI - [Changes in bone marrow among HIV-positive and HIV-negative parenteral drug addicts]. AB - BACKGROUND: The aim of the present was to study the cytohistology of the bone marrow in intravenous drug addicts (IVDA) and to analyze the possible differences according to the period of drug addiction. METHODS: A prospective study was performed in 60 IVDA patients previously untreated and distributed into three groups: 20 seronegative for the human immunodeficiency virus (HIV), 20 patients in a phase of generalized adenopathic infection (GAI) and 20 patients with AIDS. RESULTS: Cytohistologic examination of the bone marrow aspirates showed plasmocytosis and eosinophilia in all the groups. Selective changes were seen in the red series in 20% of the HIV negative patients and in 25% of the GAI group. The prevalence of cytologic changes was greater in those with AIDS, with hypocellular bone marrow being observed in 65% of the patients with coexistent dismyelopoietic changes in 15%. Pathologic structure showed granulomatous lesions of tuberculous etiology in 30% of the patients with AIDS while in the HIV negative and GAI groups these were found in 10% and 5%, respectively. A greater presence of fibrosis and bone marrow hypoplasia was also found in the group with AIDS, than in the other two groups. CONCLUSIONS: An increased number of bone marrow changes and progressive bone marrow hypocellularity may be observed on advancement of the clinical stages in intravenous drug addict patients. The incidence of tuberculous granulomas is higher in the AIDS group. PMID- 7877372 TI - [Intestinal microsporidiosis in patients with AIDS: study of 3 cases]. AB - Enterocytozoon bieneusi is a protozoa belonging to the Microsporidia family which prevalence has increased in AIDS patients. Although diagnosis is performed by the demonstration of the parasite in the epithelium of the small intestine by light and electron microscopy, techniques allowing diagnosis from stools or duodenal or biliary aspirates have recently been described. Three cases of intestinal microsporidiosis diagnosed by the mentioned method are reported. The patients were 3 males with chronic diarrhea of several months of evolution with an important ponderal loss. All were in advanced stages of HIV infection with CD4 lymphocyte counts lower than 0.1 x 10(9)/l. In all the patients in whom intestinal absorption tests were performed these were found to be altered. One of the patients presented concommitant cholestasis with parasitation by E. bieneusi being demonstrated as by the biliary route in this patient. Confirmation of infection by E. bieneusi was performed in the 3 cases by electron microscopy study of stools. A review of intestinal microsporidiosis in AIDS patients is carried out and the therapeutic possibilities available for this infection are discussed. PMID- 7877373 TI - [Distribution of headache by diagnosis as the reason for neurologic consultation]. AB - BACKGROUND: The aim of this study was to analyze the diagnostic distribution of patients consulting because of headache in a neurology department. METHODS: The clinical records of 3,498 patients who had consulted specifically due to headache between 1978 to 1993 were retrospectively studied. Diagnosis was reclassified according to the criteria of the new headache classification with data concerning the age of onset and sex distribution also being collected. RESULTS: The most frequent diagnoses were migraine (1,802 patients; 52%) tension-type headache (113; 32%), followed in decreasing order by trigeminal neuralgia, post injury headache, cluster headache, subarachnoid hemorrhage, analgesic-ergotamine abuse headache, tumoral headache, cervical disease headache, benign exertional headache, due to paranasal sinusal disorders and benign intracranial hypertension. Female predominance was observed in the whole series (68%) as in the groups with migraine, tension-type headache, neuralgia headache by analgesic ergotamine drugs and benign intracranial hypertension. Cluster, post injury, tumor and provoked headaches (cough, exertional and sexual) were found to be more frequent in men. The age of onset was very specific for each kind of headache. The percentage of symptomatic headaches increased in direct relation to age, being 10 fold higher in patients over the age of 65. CONCLUSIONS: The diagnostic distribution of headache as a cause of medical consultation is very different to the prevalence of different headaches. This distribution by diagnosis largely depends on the age of the patient at the time of headaches onset [corrected]. PMID- 7877374 TI - [10 Year follow up of chemotherapy and surgery on the second laparotomy in advanced ovarian cancer]. AB - BACKGROUND: Advanced ovarian neoplasm has bad prognosis. There is little knowledge as to the effect of surgical and chemotherapy treatments on long-term survival. METHODS: Seventy-two patients with advanced epithelial ovary carcinoma (53 stage III and 19 stage IV) were treated according to a treatment regimen with reduction surgery, five cycles of chemotherapy with cyclophosphamide, adriamycin and cisplatin (CAP) followed by second revision laparotomy. RESULTS: The rate of response for the CAP schedule was 80%, of which 16 patients (23%) showed complete response (CR), 7 (10%) partial microscopic response (PMiR) and 33 (47%) partial macroscopic response (PMR). Complete resection of residual masses was performed on the second laparotomy in 14 of the 33 patients with parital response. The median survival for all the group was 36 months with overall actuarial survival of 27% at 10 years. The survival of the group of patients with CR was significantly longer than that of PMiR and other groups. Significant differences favorable for the group of partial response with second attempt radical surgery were found versus the group in which te second surgical resection was not radical. FIGO III stage and prechemotherapy tumor size less than 5 cm were found to have favorable effect in the rate of response and survival. CONCLUSIONS: The use of CAP chemotherapy achieved complete response in 23% of the patients studied. This group of patients showed to have a greater probability of longer survival. Second attempt surgery on the second laparotomy offers therapeutic benefits when radical. PMID- 7877375 TI - [Errors in bibliographic references: a retrospective study in Medicina Clinica (1962-1992)]. AB - BACKGROUND: Misspellings of transcription or the copy of references of articles published in the literature without verifying the information with the original document may be the cause of incorrect citations. The purpose of this study was to determine the accuracy of citations to journal articles in 1962 to 1992 volumes of Medicina Clinica. METHODS: A method of systematic sampling was used to choose five references for each of the 12 original articles per year selected at 5-year intervals (1962, 1967, 1972, 1977, 1982, 1987, 1992). In the final sample of 420 references, errors in the six standard bibliographic elements--authors' names, article title, journal title, year, volume number, and page numbers--were analyzed. Major errors were defined when inaccuracies prevented identification of the cited article. RESULTS: Of the total 368 references verified, 132 (35.86%) were error free and the remaining 236 (64, 13%) were inaccurate. Multiple errors were found in 45% of cases. The mean number of errors per references was 1.13. Twelve references were incorrect, 221 errors were found in the authors' name, 131 in the title of the article, 14 in the name of the journal, 5 in the year of publication, 12 in the number of the volume, and 22 in the initial or final pages of the article. Major errors were detected in 94 (22.54%) cases and minor errors in 323 (77.45%). There were no statistically significant differences in the variation of the overall percentage of errors throughout the study period. CONCLUSIONS: A high rate of citation errors has been also documented in a Spanish medical journal. The importance of reference verification should be emphasized and authors should exercise more care in preparing bibliographies of their articles. PMID- 7877376 TI - [Cephalgia, a headache for the physician]. PMID- 7877377 TI - [Immunologic dysfunction and HIV]. PMID- 7877378 TI - [Hepatic mesenchymatous hamartoma presenting in an adult patient]. AB - Mesenchymatous hamartoma is a benign liver tumor characteristically found in childhood, particularly during the first two years of life. A case of mesenchymatous hamartoma detected in a 23-year-old female during a study for non specific abdominal disturbances is presented. Imaging techniques showed a large mass in the right hepatic lobe with hypodense areas of cystic appearance. Pathologic study demonstrated the characteristic mixoid mesenchymatous component with areas of cyst formation and rests of liver tissue inside the tumor. Despite its rarity in adults this case demonstrates the need to consider mesenchymatous hamartoma in the differential diagnosis of hepatic masses in adults, particularly when radiologic examination demonstrates cystic components. PMID- 7877379 TI - [The role of zidovudine and cesarean section in the prevention of vertical transmission of HIV]. PMID- 7877380 TI - [A new international classification of lymphoid neoplasms. Farewell to the Working Formulation, Kiel and company?]. PMID- 7877381 TI - [Fever, adenopathies, hepatosplenomegaly and cutaneous lesions in a 31-year-old woman with human immunodeficiency virus infection]. PMID- 7877382 TI - [Primary lateral sclerosis in an AIDS patient. Magnetic resonance imaging]. PMID- 7877383 TI - [Empyema caused by Gemella morbillorum]. PMID- 7877384 TI - [Myocardiopathy, mental retardation and autophagic vacuolar myopathy]. PMID- 7877385 TI - [A new case of idiopathic T CD4+ lymphocytopenia and opportunistic infection without HIV infection]. PMID- 7877386 TI - [Spontaneous bacterial peritonitis due to Listeria monocytogenes]. PMID- 7877387 TI - [Spontaneous spleen rupture and liver cirrhosis]. PMID- 7877388 TI - Low back pain. AB - Low back pain is a common reason for physician visits and is associated with enormous costs to health care and industry. Radiographic abnormalities of the lumbar spine, including disk protrusion, are common in asymptomatic subjects and only loosely associated with symptoms and neurologic examination. Therefore, highly selective evaluation is required to avoid subjecting patients with back pain to unnecessary tests and surgical procedures. Reassurance about the favorable prognosis of low back pain is an important component of therapy. Most patients with simple back pain recover with symptomatic treatment. Plain radiographs are indicated for evaluation of patients with radiculopathy and those with risk factors for underlying medical conditions. The majority of patients with back pain, even those with radiculopathy, improve with conservative management and surgery is unnecessary. Surgical consultation and CT or MR imaging scans are indicated for patients with persistent or progressive neurologic deficits or persistent sciatica with nerve root tension signs. Acute radiculopathy with bilateral neurologic deficits, saddle anesthesia, or urinary symptoms is suggestive of cord compression or cauda equina syndrome and requires urgent surgical referral. PMID- 7877389 TI - Joint pain. AB - This article reviews the approach an internist might take with a patient with joint pain. It emphasizes aspects of the history and physical examination that help yield a diagnosis. The use of simple laboratory tests is reviewed, and common questions are answered. Some general management issues are discussed, although disease-specific therapy is beyond the scope of this article. It is hoped that this article will help an internist successfully diagnose most patients who present with joint pain. PMID- 7877390 TI - Headaches. AB - Headaches are a common problem that can be disabling. The clinical features and treatment of migraine, cluster, and tension headaches are presented in this article. Emphasis is placed on the newer drugs available for acute and prophylactic treatment of these headaches. Features of headaches associated with intracranial aneurysms, temporal arteritis, cerebrovascular accidents, brain tumors, and temporomandibular disorders are also discussed. PMID- 7877391 TI - Noninsulin-dependent diabetes mellitus. The prevention of complications. AB - The microvascular complications of retinopathy, nephropathy, and neuropathy are less prevalent, and not as severe, in NIDDM as compared with IDDM for unknown reasons. Macrovascular disease is the greatest challenge in the management of NIDDM because it is the cause of death in 50% to 60% of this patient population. Control of the hyperglycemia is the most important because the prevention of complications is more effective than the treatment of them. Blood glucose control through diet, exercise, and medication is the key to reducing the previously identified complications. Lifestyle modifications of diet and exercise are the most effective treatment to reduce hyperglycemia. It is important to emphasize during the asymptomatic period the serious consequences of the complications and to set goals using the glycosylated hemoglobin. If these goals are not met, treatment should be intensified by more frequent visits or referral for the team approach. The time for intervention is before the complications are present, not after they occur. It is certainly reasonable to reduce as many risk factors as possible that adversely affect the complications of NIDDM. Hypertension can affect the course of coronary artery disease, retinopathy, nephropathy, and neuropathy and should be treated. The avoidance of tobacco is a must for the prevention of vascular disease and is associated with painful neuropathy. Dyslipidemia is seen frequently in NIDDM and should be assessed by fasting lipid panel and treated to lower the LDL cholesterol below 130 mg/dL. Reduction of individual risk factors is the most effective approach to this complex clinical syndrome until such time as a better understanding of the pathophysiology provides a more specific and effective intervention. PMID- 7877392 TI - Involuntary weight loss. AB - Involuntary weight loss is a common finding and one associated with increased morbidity and mortality, especially in the elderly patient. The precise mechanisms by which weight loss occurs are currently being elucidated and probably involve the actions of classic hormones as well as cytokines, such as TNF (cachectin), adipsin, and interleukin-1 and interleukin-6. The differential diagnosis of involuntary weight loss is extensive, but case studies indicate that cancer, depression, and disorders of the gastrointestinal tract may be the most common causes. In approximately 25% of cases, no cause of weight loss is found despite extensive evaluation and prolonged follow-up. In the majority of cases, history, physical examination, and limited laboratory and radiologic studies reveal the cause of weight loss, when a cause is to be found. If an initial evaluation does not identify a cause, careful follow-up rather than undirected diagnostic testing is recommended. In the treatment of patients with involuntary weight loss, the underlying medical or psychiatric cause of the weight loss should be treated first if possible. Several medications are currently being investigated for treatment of patients with weight loss. PMID- 7877393 TI - The chronically fatigued patient. AB - This article illustrates that the diagnostic evaluation as well as the management of the patient presenting with chronic fatigue can be done in an orderly manner. If a medical illness is the cause of the patient's fatigue, this is usually evident on initial presentation. A thorough history and complete physical examination, in conjunction with some screening laboratory tests, can rule out most medical causes of fatigue, and any remaining cases declare themselves over the next several visits. If a medical cause is not evident, a further "fishing expedition" is fruitless. Psychiatric illness, such as depression or generalized anxiety disorder, accounts for another significant proportion of cases of chronic fatigue. As with medical illness, psychiatric illness should be suspected based on history and is not a diagnosis of exclusion. Some patients presenting with chronic fatigue have a history and symptom pattern consistent with the diagnosis of CFS. The cause of this syndrome is controversial and is still unknown. The clinician, however, can offer the patient care in an environment that is respectful of their physical and psychological discomfort and can provide significant symptomatic improvement to the patient. Lastly, some patients with fatigue do not fit any diagnostic category, including CFS. As with many other common complaints, such as headaches or abdominal pain, although a diagnosis may not be given to the patient, the clinician can do a lot to reassure the patient and assist the patient in living with his or her symptoms. As Solberg eloquently wrote: "[E]valuation of the fatigued patient requires all of a physician's best attributes--a broad view of disease, psychosocial sensitivity, and a good ongoing relationship with the patient." PMID- 7877394 TI - Abnormal uterine bleeding. AB - Concerns about abnormal menstrual bleeding are a common reason for women to consult a primary care physician. The first step in the evaluation is to determine the patient's ovulatory status. Women with heavy bleeding but normal ovulatory cycles should be evaluated for coagulopathies, structural lesions, and hypothyroidism. In the absence of a systemic or structural cause, menorrhagia can be treated with OCPs or NSAIDs. Intermenstrual bleeding in OCP users may be due to noncompliance or the use of low-dose pills. Encouraging patient compliance and adjustment of the estrogen dose can often solve the problem. If the patient is not on OCPs, intermenstrual bleeding is usually due to a structural or inflammatory lesion. The differential diagnosis for anovulatory bleeding is extensive. Pregnancy, systemic illnesses, and structural lesions should be ruled out by history, physical examination, and laboratory evaluation. Endometrial biopsy is indicated in patients over age 35 and younger patients with risk factors for endometrial cancer, such as chronic anovulation and obesity. Dysfunctional uterine bleeding is a nonspecific term for abnormal uterine bleeding in the absence of systemic or structural disease. It is usually associated with anovulation. Adolescents frequently have dysfunctional uterine bleeding owing to immaturity of the hypothalamic-pituitary-ovarian axis. Perimenopausal women have an increased incidence of irregular bleeding secondary to decreased estrogen production by the ovary. Obesity, polycystic ovary syndrome, stress, crash diets, and vigorous exercise can all disrupt normal ovulatory function. Treatment options for dysfunctional uterine bleeding include oral contraceptives, cyclic progesterone, or hormone replacement with estrogen and progesterone. Patients with structural lesions or those who do not resume normal withdrawal bleeding patterns on hormone therapy should be referred to a gynecologist for further evaluation and treatment. PMID- 7877395 TI - Management of the abnormal Papanicolaou smear. AB - Screening for cervical neoplasia has been effective in decreasing invasive cervical cancer. As the understanding of the association of HPV with cervical neoplasia increases, new screening interventions may be developed. Classification of cytologic abnormalities and the management of abnormal smears continue to evolve. Ancillary screening techniques such as HPV typing and cervicography may be useful but need further study. PMID- 7877396 TI - Chronic cough. AB - Chronic cough is a common symptom presenting to all clinicians. Every effort should be made to determine the cause(s) of cough because specific therapy has a higher likelihood of success than empiric therapy. Evaluation begins with a complete history, physical examination, routine health screen laboratory testing, chest film, and pulmonary function testing. Further investigation should be guided by the response to treatment of the most likely diagnostic possibilities: postnasal drip, cough-variant asthma, gastroesophageal reflux, chronic bronchitis, bronchiectasis, and ACE inhibitor induced. The majority of each patient's workup can be performed and ordered by the primary care physician. PMID- 7877397 TI - Irritable bowel syndrome. Managing the patient with abdominal pain and altered bowel habits. AB - Irritable bowel syndrome is a common complex of syndromes thought to be generated by a motility or sensory disturbance of the gastrointestinal tract. It is a frequent cause of chronic abdominal pain and altered bowel habits. Patients who seek medical attention for irritable bowel syndrome often do so because of psychosocial factors. Therapy remains largely empirical, directed toward the relief of symptoms in the context of a supportive physician-patient relationship. PMID- 7877398 TI - Office management of common sleep-wake disorders. AB - The prevalence of sleep disorders manifest as insomnia and fatigue of excessive daytime sleepiness in the general population; office practice is high. Poor quality sleep may pose a significant health risk for not only the patient but society in general. Sensitivity for potentially serious sleep disorders should be coupled with an organized approach to diagnosis and therapy. Differentiation of the principal complaint into insomnia versus hypersomnia and determination of duration are the key elements. Office-based management of the most common sleep wake disorders and current diagnostic testing standards are discussed. PMID- 7877399 TI - Assessment and treatment of impotence. AB - Impotence is a common problem. History is primarily relied on to diagnose psychogenic impotence. Sex therapy is an effective treatment. Antihypertensive and psychiatric medicines often cause impotence, but most medicines should be considered a cause if this is supported by the history. Hormonal causes should be suspected in a patient with decreased libido or decreased testicular size, and testosterone should be measured in these cases. Hormone replacement may restore sexual function in hypogonadal men. Doppler sonogram or arteriography should be used to diagnose vascular impotence for men who would be good surgical candidates. Only young men without other illness are considered. There is little need to test neurologic function because there is no specific treatment for neurogenic impotence. These patients and patients who do not respond to the aforementioned treatments should be offered the vacuum erection device, penile self-injection therapy, or penile prosthesis. Choice depends on comorbid illness as well as patient preference. A basic algorithm for the evaluation and treatment of impotence is given in Figure 2. PMID- 7877400 TI - The outpatient with unilateral leg swelling. AB - Approaching the patient with unilateral leg swelling presents a challenge to the physician in ambulatory practice. Contributing to the difficulty is the lack of studies that have assessed a population of patients presenting with unilateral leg swelling. The purpose of this article is to discuss unilateral leg swelling with respect to the chronicity of the presentation and the most common differential diagnoses based on a review of the current literature and personal clinical experience. PMID- 7877401 TI - Approach to the patient with palpitations. AB - Palpitations are a common complaint present in up to 16% of outpatients. They are nonspecific and in only 15% of patients do they correlate with a cardiac arrhythmia. The significance of palpitations is related to the presence or absence of underlying cardiac disease, the clinical setting in which palpitations occur, and the characteristics and severity of symptoms. This article presents a concise approach to the evaluation of the ambulatory patient with palpitations. PMID- 7877402 TI - The politics and ideology of non-restraint: the case of the Hanwell Asylum. PMID- 7877403 TI - The influence of the Roman Catholic Church on midwifery practice in Malta. PMID- 7877404 TI - Listerism, its decline and its persistence: the introduction of aseptic surgical techniques in three British teaching hospitals, 1890-99. PMID- 7877405 TI - Beriberi, vitamin B1 and world food policy, 1925-1970. PMID- 7877406 TI - The reception of Paracelsianism in early modern Lutheran Denmark: from Peter Severinus, the Dane, to Ole Worm. PMID- 7877407 TI - A triumph of identity politics. PMID- 7877408 TI - Management of the internal carotid artery during carotid body tumor surgery. AB - Patients with carotid body tumors require accurate preoperative assessment of vessel involvement and the probable impact of interrupting blood flow through the internal carotid artery. Recent developments in imaging, methods of measuring cerebral blood flow, balloon occlusion testing, and techniques to maintain vascular flow when a graft is required have improved the surgeon's ability to completely resect these tumors with reduced complications. We discuss these methods with respect to our review of 20 carotid body tumors in 18 patients. Twenty-five percent of patients were misdiagnosed, and in four patients injury to the vessel wall required appropriate surgical intervention. PMID- 7877409 TI - Insulin-dependent diabetic microangiopathy in the inner ear. AB - Thickening of the basement membrane in capillaries is implicated in the microangiopathic complications of diabetes mellitus. This study was designed to evaluate microangiopathic changes of the inner ear associated with insulin dependent diabetes mellitus (IDDM) and concurrent moderate-intensity noise exposure. Male Sprague-Dawley rats were injected with streptozotocin (65 mg/kg) to induce IDDM. Half of the control and diabetic animals were exposed to chronic noise of 95 dB over the 6-month study period. Photomicrographs of the capillaries in the stria vascularis were obtained by transmission electron microscopy, and basement-membrane thickness was measured with an image processing system. This study quantitatively demonstrates basement-membrane thickening consistent with diabetic microangiopathy in the inner ear of IDDM rats. Noise exposure did not significantly change basement-membrane thickness in either diabetic or control animals. PMID- 7877410 TI - Comparison of topical fibrin glue, fibrinogen, and thrombin in preventing seroma formation in a rat model. AB - Fibrin glue has been shown to decrease seroma formation in animal models. To further delineate this mechanism, the efficacy of fibrin glue was compared to topical fibrinogen and thrombin in preventing postoperative seromas. A model consistently producing seromas was developed by bilateral neck dissection, lymphadenectomy, and submandibular sialoadenectomy in the Sprague-Dawley rat. Groups of 20 rats underwent this procedure and were blindly treated with either fibrin glue, fibrinogen, thrombin, or saline control. Necropsy on postoperative day 5 revealed a statistically significant (chi-squared) decrease in seroma incidence using fibrin glue (0%) and fibrinogen (15%), while thrombin (95%) and saline (100%) were ineffective in preventing seromas. The use of fibrin glue and fibrinogen in this role merits further investigation. PMID- 7877411 TI - Prophylactic antibiotic use in clean, uncontaminated neck dissection. AB - A recent report in the literature cites a 10% wound infection rate for clean, uncontaminated neck dissections in patients who did not receive antibiotic prophylaxis as compared with a 3.3% infection rate in patients who received prophylactic antibiotics. Although a trend favoring antibiotic prophylaxis was identified, the duration of therapy was not considered. The present analysis addresses this issue. The authors retrospectively reviewed the records of 120 patients who underwent clean, uncontaminated neck dissections over a 3-year period (July 1989 through May 1992) for variables related to wound infections. Radiation therapy had previously been used in 70% of these patients. Group 1 (31 patients) received 24 hours of perioperative antibiotic prophylaxis, and group 2 (89 patients) received antibiotic prophylaxis until the suction drains were removed (usually 4 or 5 days after surgery). No perioperative wound infections occurred in either group. The authors concluded that perioperative antibiotic prophylaxis for 24 hours is sufficient to prevent wound infections in clean, uncontaminated neck dissections. PMID- 7877412 TI - Detection of metastases from head and neck cancers. AB - Before treatment for head and neck malignancies is begun, a search for distant metastases (DM) is performed. The first objective of this review was to determine the accuracy of liver function tests (LFT), alkaline phosphatase (AP) tests, and chest radiographs (CXR) in detection of DM. Second, an effort was made to identify tumor characteristics which are associated with a higher incidence of DM and therefore justify the use of more precise screening tools. An analysis of 97 patients with noncutaneous squamous cell carcinomas presenting to the Stanford Head and Neck Tumor Board in 1991 revealed 17 DM in 14 patients. There were 10 pulmonary metastases, 5 bone metastases, and 2 hepatic metastases. CXR had a sensitivity of 50% and a specificity of 94% for detection of pulmonary DM. AP tests showed a sensitivity of 20% and a specificity of 98% for detection of bone DM. LFT had a sensitivity of 50% and an 81% specificity for demonstration of hepatic DM. A separate analysis of 79 patients with known DM from two hospitals showed the incidence of DM to be increased in patients who had tumors of advanced stage, advanced T status, and poor histologic differentiation and to also be increased in the presence of local-regional recurrence. There was little association of DM with N status. The sensitivity of CXR and laboratory tests, which are currently used in evaluation for DM at most cancer centers, is disappointing; these tests should be viewed as gross screening examinations. We recommend a chest computed tomography scan in the event of an abnormal CXR, a bone scan in the event of an elevated AP, and either an ultrasound or computed tomography/magnetic resonance imaging scan of the liver when elevated LFT levels are present, depending on tumor stage and differentiation. PMID- 7877413 TI - Quantitative measures of laryngeal function following Teflon injection or thyroplasty type I. AB - Laryngeal/voice function was evaluated in six patients with unilateral true vocal fold paralysis following treatment with Teflon injection (TEF) compared to six patients treated with thyroplasty type I (THY). Auditory perceptual, aerodynamic, and endoscopic assessments were conducted. Three judges rated nine voice characteristics. Aerodynamic measures included estimated subglottal pressure, airflow, and laryngeal resistance. Two judges rated laryngeal characteristics from flexible fiberoptic assessment. The THY group had significantly better voice quality and better quantitative aerodynamic findings compared to the TEF group. The TEF group also was more likely to have an irregular vocal fold edge, an irregular glottal closure pattern, a higher occurrence of hyperfunction and hypertrophy of the false vocal folds, edema, and erythema of the paralyzed folds. Results suggest that THY was associated with more favorable measures of laryngeal/voice function than TEF. It is likely that the poorer perceptual, aerodynamic, and endoscopic findings associated with TEF injection may be due to violation of the true vocal fold cover, particularly increased true vocal fold mass and stiffness. PMID- 7877414 TI - Congenital aural cholesteatoma: results of surgery in 60 cases. AB - From 1978 to 1993, 59 patients (60 ears) with congenital middle ear cholesteatoma were treated at the House Ear Clinic. The median patient age at presentation was 5 years, and the period of postoperative follow-up was 4.8 years. An intact canal wall was maintained in 58 of 60 cases and a closed middle ear space in all cases. In 12 operations, lateral graft tympanoplasty eradicated the cholesteatoma in one stage; 32 patients required a second-stage surgery to rule out recurrence, and the remaining 16 cases required three or more operations to eradicate disease and reconstruct the hearing mechanism. Thirty-five (63%) of 56 patients had a postoperative air-conduction threshold pure-tone average (PTA) within 10 dB of the best bone-conduction PTA; 91% were within 20 dB. Average speech reception threshold improved from 32 dB hearing level (HL) preoperatively to 20 dB HL postoperatively. PMID- 7877415 TI - Posterior semicircular canal occlusion for benign paroxysmal positional vertigo- CO2 laser-assisted technique: preliminary results. AB - Benign paroxysmal positional vertigo (BPPV) is a common vestibular end-organ disorder that in the majority of patients resolves with conservative management. In the occasional patient who has unremitting BPPV despite conservative treatment, posterior semicircular canal occlusion (PCO) may be effective in eliminating symptoms. In an attempt to minimize the risk of hearing loss, a modified procedure was developed that uses the CO2 laser to shrink the membranous vestibular posterior semicircular canal prior to mechanically plugging the canal. Preliminary results of this CO2 laser-assisted occlusion technique used in four patients are presented. PMID- 7877416 TI - Acoustic rhinometry in the evaluation of nasal obstruction. AB - Acoustic rhinometry (AR) is a recently developed objective technique for assessment of geometry of the nasal cavity. The technique is based on the analysis of sound waves reflected from the nasal cavities. It measures cross sectional areas and nasal volume (NV). To obtain dependable assessments of nasal resistance by rhinomanometry or cross-sectional area measurements by AR, it is essential that the structural relations of the compliant vestibular region remain undisturbed by the measuring apparatus. The use of nozzles in making these measurements carries a great risk of direct distortion of the nasal valve. We used a nasal adapter that does not invade the nasal cavity and a chin support that stabilizes the head. In 51 healthy nasal cavities, the average minimum cross sectional area (MCA) was 0.62 cm2 at 2.35 cm from the nostril and 0.67 cm2 at 2 cm from the nostril, respectively, before and after topical decongestion of the nasal mucosa. The MCA and NV findings in this group were significantly higher than MCA and NV (P < 0.001) in people with structural or mucosal abnormalities before mucosal decongestion. After mucosal decongestion, the MCA and NV were significantly higher in healthy nasal cavities than in nasal cavities with structural abnormalities (P < 0.001) but were not higher than nasal cavities with mucosal abnormalities (MCA, P = 0.05; NV, P = 0.06). A nozzle was applied in 20 healthy nasal cavities after mucosal decongestion, and a significantly higher MCA was found compared to measurements made with the nasal adapter (P = 0.02). We conclude that the nasal adapter, which does not invade the nasal cavities, avoids the distortion of the nasal valve and gives more accurate results. PMID- 7877417 TI - Inverted papilloma: a report of 112 cases. AB - Inverted papilloma is a benign sinonasal tumor which is locally aggressive and has a significant malignant potential. This report updates the experience of the two senior authors, who have treated 112 patients with inverted papilloma at the Mount Sinai Medical Center over a 20-year period. As clinical examination often underestimates tumor extent, preoperative radiographic assessment is of paramount importance in guiding selection of surgical therapy. Complete en bloc excision via lateral rhinotomy and medial maxillectomy was the method of treatment in the majority of patients (84%). In selected patients with limited disease, or in patients who refused en bloc excision, conservative therapy employing intranasal or transantral ethmoidectomy was performed. The recurrence rates for the two groups were 14% and 20%, respectively. Recurrent disease developed throughout the paranasal sinuses, with the maxillary antrum and ethmoid labyrinth constituting the major sites. In two patients presenting with anterior skull base erosion, craniofacial resection was undertaken to eradicate disease. The latter cases underscore the aggressive nature of the tumor if left untreated. The overall rate of squamous carcinoma in this series was 5%. Given the predilection for local recurrence, multicentricity, and the possibility of malignancy, the authors continue to recommend lateral rhinotomy and medial maxillectomy as the standard therapy for the majority of cases. Management principles as well as a review of the literature are discussed. PMID- 7877418 TI - Sensorineural hearing loss in patients with large vestibular aqueduct. AB - In examining 181 patients (327 ears) with sensorineural hearing loss of unknown etiology and 25 people (50 ears) with normal hearing by high-resolution computed tomography (CT), the image of the large vestibular aqueduct (VA) was defined as being a visible large aperture (> or = 4 mm), and small distance between vestibule and traceable part of the VA nearest to the vestibule (> or = 1 mm). The large VA was found in 13 patients (23 ears, 7.0%); it was relatively frequent following hypoplastic cochlea (33 ears, 10.1%) in all the inner ear anomalies detected. In patients with large VA, high-frequency hearing was affected more than low frequency, and history of sudden hearing loss was observed frequently (61% of ears with large VA), which was found to be triggered by characteristic episodes such as minor head trauma, etc. Those clinical features were observed more in those without cochlear anomaly than in those accompanying cochlear anomaly. Pathogenesis of sensorineural hearing loss and characteristic fluctuation of hearing in those patients are discussed. PMID- 7877419 TI - Respiratory epithelium exposed to sulfur dioxide--functional and ultrastructural alterations. AB - The value of morphological investigations of airway mucosa should be compared to a functional method when estimating the toxicity of airborne pollutants. In 34 guinea pig tracheas, mucociliary activity was measured using a modified light beam reflex method before and following exposure to sulfur dioxide for 30 minutes in concentrations ranging between 7.5 and 37.5 mg/m3. Exposure to air served as a control. Simultaneously, specimens were taken for light and electron microscopy. Mucociliary activity decreased from 8.4 +/- 2.9 Hz (control exposure) to 4.0 +/- 2.9 Hz following exposure to 7.5 mg/m3, to 3.4 +/- 2.7 Hz at 15 mg/m3 sulfur dioxide, to 1.8 +/- 2.2 Hz at 22.5 mg/m3 sulfur dioxide, to 1.5 +/- 1.8 Hz at 30 mg/m3 sulfur dioxide, and to 2.0 +/- 1.2 Hz at 37.5 mg/m3 sulfur dioxide, respectively (P < .01). Despite a 56% decrease in mucociliary activity, only minor morphological alterations were observed following exposure to 7.5 mg/m3 sulfur dioxide. However, following exposure to 15 mg/m3 sulfur dioxide or higher, structural alterations of respiratory mucosa such as epithelial sloughing, intracellular edema and mitochondrial swelling, widened intercellular space, and ciliary cytoplasmic extrusions were found. Thus measurement of mucociliary activity proved to be a more sensitive indicator of airway toxicity than structural investigations alone. PMID- 7877420 TI - Streptococcus pneumoniae resistant to penicillin: incidence and potential therapeutic options. AB - Streptococcus pneumoniae was recovered from 12 (50%) samples of middle ear fluid of 24 consecutive patients with AOME and in mixed culture of middle ear pathogens from one (4%) additional specimen. Two (15.3%) isolates had intermediate resistance to penicillin (minimal inhibitory concentration (MIC) 0.125 and 1.0 micrograms/mL). The antimicrobial susceptibility to various antimicrobials of 30 S pneumoniae strains recovered from patients seen in the last 12 months was also determined. One of the patients with AOME developed bacteremia that resolved uneventfully, whereas the other developed meningitis. MIC90 was determined from penicillin (2 micrograms/mL), erythromycin (> 32 micrograms/mL), cefaclor (32 micrograms/mL), loracarbef (> or = 64 micrograms/mL), cefixime (16 micrograms/mL), ceftibuten (> 64 micrograms/mL), chloramphenicol (16 micrograms/mL), cefpodoxime (4 micrograms/mL), ciprofloxacin (2 micrograms/mL), cephalexin (> or = micrograms/mL), augmentin (2 micrograms/mL), cefprozil (8 micrograms/mL), clindamycin (64 micrograms/mL), TMP-SXT (> 64 micrograms/mL), clarithromycin (32 micrograms/mL), rifampin (0.06 micrograms/mL), cefuroxime (2 micrograms/mL), cefotaxime (0.25 micrograms/mL), vancomycin (0.25 micrograms/mL), and imipenem (0.5 micrograms/mL). Cefprozil, vancomycin, and rifampin inhibited all strains, whereas cefpodoxime, cefuroxime, clindamycin, and clarithromycin exhibited very good activity. PMID- 7877421 TI - Plasminogen activators in tissue extract of aural cholesteatoma. AB - Using a biochemical technique, the authors characterized and identified the plasminogen activator (PA) derived from tissue extracts of six aural cholesteatomas. The results of fibrin zymography indicated that the tissue extracts of two cholesteatomas demonstrated two lytic zones on fibrin-agarose plates. One of the lytic zones was at about 72 kd, while the other zone was at about 64 kd. Using various goat immunoglobulin G (IgG)-containing antibodies (anti-human uterine tissue type PA (t-PA), anti-human low-molecular-weight (LMW) urokinase, and nonspecific goat IgG) and plasminogen-free fibrin-agarose plates, we confirmed that the cholesteatoma tissue extracts contained 72 kd t-PA and 64 kd urokinase type PA (u-PA). Furthermore, we measured the t-PA and u-PA activities in the tissue extracts selectively by parabolic rate assay. In order to estimate the PA activity, we developed optimal conditions for this assay. The specific t-PA activity ranged from 0.03 to 0.43 mIU/micrograms-protein and the specific u-PA activity ranged from 0 to 0.35 mIU/microgram-protein. The highest percentage of u-PA with respect to the total PA activity was 44.9%. However, in four of the six cases, we failed to detect u-PA activity. In the present study, we thus clarified the presence of PAs in tissue extracts of aural cholesteatomas. Furthermore, we confirmed that measureable u-PA occurred in some tissue extracts. We anticipate that the u-PA in inflammatory tissues plays an important role in the degradation of the extracellular matrix via the formation of plasmin and collagenases. PMID- 7877422 TI - Predictors of outcome for uvulopalatopharyngoplasty. AB - The objective of this study was to assess the value of preoperative fiberoptic nasopharyngoscopy with the Muller maneuver (FNMM) and cephalometric radiography in predicting response to uvulopalatopharyngoplasty (UPPP) in patients with obstructive sleep apnea syndrome. Fifty-three such patients having significant obstruction at the soft palatal level and variable degrees of obstruction at the base-of-tongue level underwent both diagnostic procedures before UPPP. Outcome was assessed by the apnea-plus-hypopnea index (AHI) as determined by polysomnography, which was performed before and after surgery. As a group, patients exhibited a significant 10-point reduction in AHI (46.5 to 36.7). However, 17 (32.1%) were judged to be responders as defined by a reduction of the AHI by an increment of 50% or greater with respect to baseline. Of all the cephalometric variables assessed, soft palate length was the only one that differed between responders and nonresponders (45.5 mm versus 42.6 mm, respectively). However, this difference only approached significance (P = .067). Similarly, FNMM results did not discriminate between responders and nonresponders. These results indicate that preoperative cephalometric radiography and FNMM cannot be reliably used to enhance surgical success. PMID- 7877423 TI - Care of the terminal head and neck cancer patient in the hospice setting. AB - The ratio of incidence to mortality is somewhat less than 3:1 for head and neck cancer, and the 5-year relative survival rate is 50%. Despite the high mortality rate, few reports have focused on patients with terminal head and neck cancer. A growing number of these patients end their lives in a hospice facility. A retrospective analysis was undertaken of 67 patients with terminal head and neck cancer who were admitted to the Tel Hashomer Hospice between 1988 and 1992. Patient data were reviewed and analyzed, and the particular characteristics of this population were defined. This study found that terminal head and neck cancer patients seem to receive better support in a hospice than in a general hospital or some family settings. PMID- 7877424 TI - Nd:YAG laser turbinate surgery animal experimental study: preliminary report. AB - The chronically hypertrophic nasal turbinate is a challenging problem for otolaryngologists. Although some success has been achieved with a number of medical and surgical methods, other forms of treatment are still needed. In this study, encouraging results were achieved using the neodymium:yttrium-aluminum garnet (Nd:YAG) laser on canine turbinates. Clinical and histological results showed that with Nd:YAG laser surgery, coagulation occurs in the deep cavernous vessels and submucosal glands of the turbinate, while the overlying mucosa remains intact. PMID- 7877425 TI - Subperichondrial cricoidectomy: an alternative to laryngectomy for intractable aspiration. PMID- 7877426 TI - Management of posterior tympanic membrane retraction. PMID- 7877427 TI - [Diagnosis of round liver lesions]. AB - Ultrasound and computed tomography are dominant in the diagnosis of liver lesions. Angiography, magnetic resonance imaging, and scintigraphic procedures complete the spectrum. Ultrasound and computed tomography are able to detect focal liver lesions and to distinguish between hypoechoic, anechoic and hyperechoic lesions. We differentiate in addition between liver lesions found accidentally or in patients suffering from a known tumor. For a definite diagnosis of a haemangioma a computerized tomography with rapid contrast bolus or MRI should be performed. If there is suspicion of an adenoma or a focal nodal hyperplasia a hepatobiliary sequence scintigraphy should be performed. In the following the essential procedures for the differential diagnosis of liver lesions based on there sonomorphological appearance is presented. PMID- 7877428 TI - [Bleeding peptic ulcers--how can recurrent bleeding be prevented?]. AB - Bleeding is the most frequent complication of peptic ulcer disease. Patients with a previous ulcer hemorrhage have a high risk for future bleeding episodes. Therefore, treatment aiming at ulcer prophylaxis is mandatory. Helicobacter pylori infection, acid/pepsin and intake of Aspirin or NSAIDs are the main causal factors involved in the pathogenesis of peptic ulcer disease. Ulcers induced by nonsteroidal anti-inflammatory drugs can be cured by gastric acid suppression (e.g. omeprazole) and prevented by withdrawal of the ulcerogenic substances or co medication with omeprazole or misoprostol. Acid and Helicobacter pylori are necessary, albeit by themselves not sufficient factors in the causal web of the formerly idiopathic, gastritis-associated peptic ulcer disease of the stomach and the duodenum. Maintenance therapy with antisecretory drugs results in a marked decrease of ulcer recurrences and probably further ulcer complications after an index bleeding, but a definite cure of the ulcer disease is not feasible in the majority of patients. The proportion of patients remaining in remission is dependent on the degree of gastric acid suppression. Therefore, potent antisecretory drugs such as the proton pump inhibitor omeprazole should be used if a physician decides to initiate a long-term maintenance therapy. Several studies have demonstrated beyond doubt that cure of Helicobacter pylori eradication resulted in a stable remission of gastric and duodenal ulcer disease. In addition, a true reinfection after apparent eradication of the bacteria has been rarely observed in adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877429 TI - [Formation of a liver abscess as the first manifestation of concealed perforated sigmoid diverticulitis]. AB - Normally colonic diverticulitis presents itself clinically with symptoms. In our presentation pyogenic liver abscess was the primary finding of a concealed perforation of sigma colon diverticulitis. Investigations, diagnostic procedures and therapy are presented. PMID- 7877430 TI - ["A defective public health office monitors health"]. PMID- 7877431 TI - [Vision and hearing disorders with omeprazole: the facts]. PMID- 7877432 TI - Kinetics of hepatic amino-nitrogen conversion in ageing man. AB - Previous studies have shown that hepatic function, quantitatively measured by dynamic liver function tests, progressively declines with ageing. Urea synthesis is a specific process taking place in the liver; a reduced urea synthesis in response to a protein-rich metal has previously been demonstrated in the elderly, but the process has never been standardized in relation to amino acid supply. We measured the hepatic conversion of alpha-amino nitrogen into urea nitrogen in response to alanine infusion in 32 subjects, with normal routine liver and renal function tests and without evidence of previous hepatic disorders, belonging to three different age-groups (< or = 55 years, 56-70, > or = 71). The functional hepatic nitrogen clearance was reduced on average by 20% in subjects aged 56-70 years, and by 30% in subjects over 70 years old in comparison to the age-group under 55 years (ANOVA: P = 0.0001), and significantly correlated with age (r = 0.684). No sex differences were observed on the effects of age on hepatic clearance. Also, liver volume, measured by ultrasonography, was reduced with advancing age, but the age-related decrease in hepatic nitrogen conversion was not primarily dependent on decreased liver volume. The measurement of functional hepatic nitrogen clearance has already been validated as a quantitative liver function test in clinical hepatology. In keeping with previous studies, the age related decline in hepatic nitrogen conversion points to a decreased functional capacity of the ageing hepatic parenchyma. PMID- 7877433 TI - Immunohistochemical analysis of retinoblastoma gene product (pRB) expression in malignant and non-malignant liver diseases. AB - The retinoblastoma gene product is a nuclear phosphoprotein that undergoes cell cycle-dependent changes in its phosphorylation status. To analyze the expression of retinoblastoma gene product in the process of liver regeneration and the initiation of hepatocellular carcinoma, we studied immunohistochemically the expression of retinoblastoma gene product and DNA polymerase alpha (DPA) in 33 patients with various liver diseases. Only a few hepatocytes positive for retinoblastoma gene product were found in undamaged, nonregenerating liver tissues, whereas many hepatocytes positive for retinoblastoma gene product were detected in specimens of regenerating liver obtained from patients with acute or chronic liver diseases. Similarities were found between distribution patterns of hepatocytes positive for retinoblastoma gene product and those of hepatocytes positive for DPA, and a highly significant positive correlation was found between the number of hepatocyte nuclei stained for retinoblastoma gene product per 1000 nuclei examined (R-LI) and the number of hepatocyte nuclei stained for DPA per 1000 nuclei examined (D-LI) in tissues obtained from patients with nonmalignant liver disease. Hepatocellular carcinoma cells positive for DPA were detected in the 14 hepatocellular carcinoma specimens tested. In ten of these specimens, hepatocellular carcinoma cells positive for retinoblastoma gene product were found but not in the other four. For all hepatocellular carcinoma specimens, R-LI was proportional to D-LI. Thus in both nonmalignant and malignant liver, retinoblastoma gene product increased in proportion to proliferation of hepatocytes or hepatocellular carcinoma cells. PMID- 7877435 TI - Effects of phalloidin and colchicine on diethylmaleate-induced choleresis and ultrastructural appearance of rat hepatocytes. AB - Diethylmaleate is used as a model compound whose glutathione conjugates are secreted into bile, and which induce choleresis and the formation of Golgi derived vesicles in hepatocytes. This study was performed to test the assumption that these vesicles are involved in the bile canalicular secretion of diethylmaleate. We reasoned that phalloidin and colchicine, two drugs acting on microfilaments and microtubules, respectively, can modify the movements of diethylmaleate-induced vesicles towards the bile canaliculus. Phalloidin induced the formation of a thick microfilamentous network around the bile canalicular plasma membrane domain. A significant decrease in diethylmaleate-stimulated choleresis was observed, associated with a striking accumulation of pericanalicular vesicles, which were confirmed by morphometric analysis. In contrast, in rats pretreated with colchicine, after diethylmaleate administration, only a few vesicles were observed around the bile canaliculus, while diethylmaleate-induced choleresis also decreased. These results suggest that: a) the thick microfilament network induced by phalloidin prevents diethylmaleate-associated vesicles reaching the bile canalicular plasma membrane; and b) colchicine produces a dispersion of these vesicles in the cytoplasm of hepatocytes by inhibiting the polymerization of microtubules. These observations support a role of vesicles in the transport of diethylmaleate by hepatocyte into bile, and are consistent with the existence of a vesicular pathway for the biliary secretion of diethylmaleate and possibly other organic anions. PMID- 7877434 TI - Long-term histologic and viral changes in patients with chronic hepatitis C who responded to alpha interferon. AB - We assessed the long-term outcome in 24 patients with chronic hepatitis C who responded to alpha interferon. All patients were followed up for 12 months, and 16 patients were followed up 41 +/- 9 months. During the follow-up period, 18 of the 24 patients (75%) relapsed (serum ALT levels increased again); 16 had an early relapse within the 6 months and two had a late relapse 21 and 36 months after therapy; one cirrhotic patient with relapse died. Serum HCV RNA remained detectable in the two patients before the late relapse and in three of the six patients with sustained biochemical response. Histologic assessment 13 to 31 months after therapy showed a decrease in activity in most patients, even in some of those with relapse, but the decrease in portal inflammation was more marked (p < 0.05) in patients with sustained biochemical response. Liver HCV RNA was not detectable in the two sustained responders who were negative for serum HCV RNA. Despite biochemical remission induced by interferon therapy, HCV replication persists in many patients with a potential risk of late relapse. In contrast, some patients have no long-term detectable HCV RNA, suggesting clearance of HCV. Long-term histologic improvement of portal inflammation in most patients confirms the beneficial effect of interferon. PMID- 7877436 TI - Human immunodeficiency virus infection and hepatitis C pathology. AB - To investigate the possible influence of human immunodeficiency virus (HIV) infection on hepatitis C virus-related liver disease, liver morphology was evaluated in 160 HBsAg-negative patients with chronic hepatitis C, including 68 HIV-positive and 92 HIV-negative cases. No differences were detected in the severity of necro-inflammatory hepatic lesions between HIV-negative and HIV positive patients when the CD4+ lymphocytes count exceeded 400 cells/mm3. In contrast, HIV-positive patients with CD4+ lymphocytes below 400 cells/mm3 showed a significantly lower grade of portal inflammation and piecemeal necrosis. These results suggest that liver lesions in hepatitis C may largely depend on immunomediated mechanisms. PMID- 7877437 TI - Biliary cystadenoma of the liver with elevated CA 19-9. AB - A case of intrahepatic biliary cystadenoma with mesenchymal stroma is reported. The tumor was associated with strikingly elevated serum and intracystic levels of the tumor-associated antigen CA19-9. Two months after surgical enucleation, serum CA 19-9 levels returned to normal. PMID- 7877438 TI - Liver lesions in cryoglobulinaemia associated with gastric non-Hodgkin lymphoma: a case report. AB - Liver lesions in cryoglobulinaemia, associated with gastric non-Hodgkin lymphoma, are described in a 67-year-old woman. Histological examination showed capillaropoiesis in some portal tracts with vessels containing amorphous, eosinophilic and PAS-positive material, which immunohistochemically was shown to contain IgM and k light-chains. PMID- 7877440 TI - Corticotropin releasing factor mRNA and peptide levels are differentially regulated in the developing ovine brain. AB - The regulation of CRF mRNA and protein in the developing ovine brain has been studied to assess the hypothesis that CRF is differentially regulated in the hypothalamus (Hypo), hippocampal-amygdala complex (H & A), frontal cerebral cortex (FCC) and brainstem (BS). We used a quantitative RNase protection assay and radioimmunoassay to determine mRNA and peptide concentrations, respectively, from the last third of gestation until term (i.e., from 95 to 142 days gestation (dg); term approximately 145 days). The major findings from this study are: (1) Hypothalamic CRF mRNA was increased by 2-fold in 140-142 dg fetuses compared to 128-138 and 95-123 dg fetuses; P = 0.016. (2) In the hypothalamus of 140-142 dg fetuses, there was a 2.5-fold increase in CRF mRNA derived from polyadenylation at poly(A) sites 2, 3 or 4; P = 0.005. (3) In 128-138 dg fetuses, CRF mRNA in the frontal cortex was 2-fold higher than in the other brain regions during this time period; P = 0.008. (4) CRF peptide concentrations in the Hypo were 2.5-fold higher in 140-142 dg fetuses compared to 95-106 and 128-138 dg fetuses; P = 0.007. (5) CRF peptide concentrations in the frontal cortex were 5.5-fold higher in 140-142 dg fetuses compared to fetuses at 95-106 dg; P = 0.004. (6) CRF peptide concentrations in the H & A were 5-fold higher in 140-142 dg fetuses compared to 95-106 dg fetuses; P = 0.029. The results from the present study demonstrate for the first time that CRF mRNA and peptide are differentially regulated in a region-specific manner during development. PMID- 7877439 TI - Cellular influences on RNA sorting in neurons and glia: an in situ hybridization histochemical study. AB - The unique structures of process-bearing cells in the central nervous system (CNS) present an ideal model with which to study the differential distribution of mRNA. We conducted a side-by-side examination of the intracellular distribution of nine neural mRNAs by in situ hybridization histochemistry in mammalian brain and observed four general types of mRNA distributions. (1) Some mRNA species were confined to cell somas and included those encoding the glial proteins, myelin proteolipid protein and 2'3'-cyclic nucleotide-3'-phosphodiesterase and the neuronal enzymes, neuron-specific enolase and glutamate decarboxylase-67. (2) Some mRNAs were found abundantly within the cell soma and were also located throughout cellular processes. These included myelin basic protein (MBP) mRNA, which was localized to the cell soma and myelin sheaths of oligodendrocytes, and glial fibrillary acidic protein (GFAP) mRNA, which was localized to the cell soma and processes of reactive and some non-reactive astrocytes in the adult brain and radial glia in embryonic brain. (3) Some mRNAs were found primarily in perinuclear cytoplasm but in some cells were also observed in cell processes. These included mRNAs encoding the protein kinase C/calmodulin-binding substrates, RC3 (neurogranin) and GAP-43, which were identified in the somas as well as within the proximal dendritic branches of specific forebrain neurons. (4) Some mRNAs were localized primarily within cell processes. These included MAP2 mRNA, which was identified by deep staining within dendritic fields but by only light staining within neuronal cell bodies. The data also indicated that the stage of cellular development and the regional location of a cell within the CNS had a profound influence on translocation events. MAP2 mRNA was found in the dendritic processes of most neurons but was confined to the soma of neurons in specific brainstem nuclei. MBP mRNA was confined to the perinuclear cytoplasm of immature oligodendrocytes and was then transported into the myelin sheath at a developmental stage corresponding to myelination. The distribution patterns of these mRNAs are likely to reflect the mechanism by which the protein products of these molecules are targeted within neurons and glia. In addition, mRNA movement may be influenced by cellular and regional factors not encoded solely within the structure of the translocated mRNA. PMID- 7877441 TI - Molecular diversity at the carboxyl terminus of human and rat tau. AB - Although a long terminal isoform of tau was historically the first identified clone, no such isform has been thus far reported among species other than mouse. We show here that there are homologues of the long terminal isoform in human and rat, but in various forms in contrast to mouse. There are generated by a combination of multiple splice sites, which causes distinct molecular diversity at the carboxyl terminus of human and rat tau. PMID- 7877442 TI - Role of kainate/AMPA receptors in induction of striatal zif/268 and preprodynorphin mRNA by a single injection of amphetamine. AB - The role of kainate/AMPA excitatory amino acid receptors in D-amphetamine (AMPH) induced behavioral changes and the induction of immediate early gene and preprodynorphin (PPD) mRNA in various regions of rat forebrain was investigated with quantitative in situ hybridization histochemistry. Three hours after a single injection of AMPH (5 mg/kg, i.p.), PPD mRNA and mRNA of the transcription factor zif/268, but not c-fos, was increased in dorsal striatum (caudate). Zif/268 mRNA was also increased in the sensorimotor cortex. Pretreatment of rats with DNQX, a kainate/AMPA receptor antagonist, did not affect the behaviors elicited by AMPH. However, the AMPH-stimulated increase in PPD and zif/268 mRNA levels in striatum, but not zif/268 mRNA in cortex, was blocked by DNQX pretreatment. In contrast, DNQX alone attenuated basal (constitutive) levels of zif/268 mRNA expression in sensorimotor cortical, but not in striatal, neurons. These studies indicate that kainate/AMPA receptors mediate the induction of zif/268 and PPD mRNA expression in the caudate nucleus induced by a single injection of AMPH. The fact that DNQX blocked genomic, but not behavioral, responses to acute AMPH suggests that kainate/AMPA receptor mechanisms may be involved in the long-term (possibly sensitizing) effects, rather than the acute effects, of the drug. In addition, tonic kainate/AMPA receptor stimulation may play a key role in maintaining constitutive expression of the zif/268 gene in cortical neurons. PMID- 7877443 TI - Stress elicits trans-synaptic activation of adrenal neuropeptide Y gene expression. AB - Stress triggers responses important to maintain internal homeostasis, and yet when prolonged can cause medical consequences that are most likely mediated by changes in gene expression. In this study we examine the alterations in gene expression of neuropeptide Y (NPY), a potent vasoconstrictor, with stress. Stressors, such as immobilization and cold, were found to increase adrenal NPY gene expression in rats. Adrenal prepro-NPY mRNA levels were elevated by a relatively short period of stress. A single immobilization was sufficient for an increase in prepro-NPY mRNA, that remained elevated for as long as one day later. This rise in adrenal NPY mRNA was abolished by the transcriptional inhibitor actinomycin D. Repeated (2 and 7) daily immobilizations led to a further rise and sustained elevations of prepro-NPY mRNA levels. This increase persisted 2-3 days after the cessation of repeated stress. The stress-elicited increase in NPY gene expression is transsynaptic requiring splanchnic innervation and mediated by nicotinic receptors. Hypophysectomy did not prevent the stress elicited rise in adrenal prepro-NPY mRNA levels. These results suggest that long lasting changes in NPY gene expression might be an important component in the homeostatic mechanisms triggered by chronic stress. PMID- 7877444 TI - GABAA receptor stimulation enhances NMDA-induced Ca2+ influx in mouse cerebral cortical neurons in primary culture. AB - The effect of GABAA receptor stimulation on N-methyl-D-aspartate(NMDA)-induced [45Ca2+]influx has been examined using primary cultured cerebral cortical neurons. NMDA induced a dose-dependent increase in [45Ca2+]influx, which was blocked by MK-801 in a dose-dependent manner. GABAA receptor agonists significantly enhanced the NMDA-induced [45Ca2+]influx, and this enhancement was dose-dependently inhibited by bicuculline, although picrotoxin and tert-butyl bicyclo[2.2.2]phosphoro-thionate (TBPS) exhibited no alterations in this stimulatory action of GABAA receptor agonists. Blockers of L-type voltage dependent calcium channels significantly reduced the NMDA-induced [45Ca2+]influx. The increased [45Ca2+]influx by both NMDA and GABAA receptor agonists was also reduced by verapamil and nifedipine. These results suggest that the enhancement of NMDA-induced [45Ca2+]influx by GABAA receptor stimulation in immature cerebral cortical neurons may be due to the increased opening of voltage-dependent calcium channel by synergestic actions between NMDA and GABAA receptors. PMID- 7877445 TI - Genomic structure and mapping of precerebellin and a precerebellin-related gene. AB - The cerebellum-specific hexadecapeptide, cerebellin, is derived from a larger precursor, precerebellin, that has sequence homology to the complement component C1qB. We report the cloning of the murine homolog of precerebellin, Cbln1, and a closely related gene, Cbln2. Amino acid comparison of Cbln1 with Cbln2 revealed that Cbln2 is 88% identical to the carboxy terminal region of Cbln1. That these are independent genes was confirmed by Southern analysis and genome mapping. Cbln1 was positioned to the central region of mouse chromosome 8, 2.3 cM distal of JunB and 6.0 cM proximal of Mt1, while Cbln2 mapped to the distal end of mouse chromosome 18, 1.7 cM telomeric of Mbp. PMID- 7877446 TI - Peripheral administration of lipopolysaccharide induces the expression of cytokine transcripts in the brain and pituitary of mice. AB - The reverse transcription polymerase chain reaction (RT-PCR) was used to assess the induction of mRNA of the proinflammatory cytokines IL-1 beta, IL-6 and TNF alpha in the spleen, pituitary, hypothalamus and hippocampus of mice after an intraperitoneal injection of lipopolysaccharide (LPS, 10 micrograms/mouse). The kinetics of cytokine gene expression induced by peripheral LPS in the pituitary and brain structures were different from that observed in the spleen. For IL-1 beta the dose-response curve was also measured and also found to be different. These results support the idea that one pathway by which peripheral immune stimuli affect brain functions includes local synthesis of proinflammatory cytokines in certain brain structures. PMID- 7877447 TI - Expression of nicotinic acetylcholine receptors in the rat superior cervical ganglion on mRNA and protein level. AB - The expression of nicotinic acetylcholine receptors (nAChR) in the rat superior cervical ganglion was investigated by Western blotting, immunohistochemistry and non-radioactive in situ hybridization applying probes for the alpha 4-1 and beta 2 subunit mRNA. Immunoblot analysis of homogenized ganglia using the anti-nAChRs antibody WF6 revealed a labeled protein band of apparent molecular weight of 40 kDa which is typical for the alpha subunit of nAChRs. Applying double-labeling immunofluorescence with antibodies against tyrosine hydroxylase, nAChR-like molecules were identified in most postganglionic neurons and in a subpopulation of small intensely fluorescent (SIF) cells. alpha 4-1 and beta 2 subunit mRNAs were detected in all perikarya of postganglionic sympathetic neurons but not in SIF cells. These results suggest that antibodies raised against purified Torpedo AChR bind to nAChR in sympathetic ganglia and indicate that alpha 4-1 and beta 2 subunits are constituents of nAChRs in sympathetic postganglionic neurons but not of SIF cells. PMID- 7877448 TI - Increased glucocorticoid receptor gene expression in the rat hippocampus following combined serotonergic and medial septal cholinergic lesions. AB - Glucocorticoid excess is associated with hippocampal neuronal dysfunction and loss, mainly affecting CA1. Degeneration of both cholinergic and serotonergic (5 HT) hippocampal afferents is prominent in aged rats and Alzheimer's disease. Lesions of these individual pathways alter hippocampal expression of mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNAs; both transcripts are increased by cholinergic lesions, but markedly decreased by serotonergic denervation. In the present study we found that combined medial septal cholinergic and central 5-HT lesions increase hippocampal GR mRNA expression, specifically in CA1 and CA2 subfields, whereas MR mRNA expression was similar to controls. Thus the effects of the cholinergic lesion, at least upon GR gene expression, appear to predominate while the effects of the lesions upon MR gene expression were additive. Increased hippocampal GR gene expression per neuron may increase hippocampal neuronal vulnerability with age or disease. PMID- 7877449 TI - Increased fearfulness of Fyn tyrosine kinase deficient mice. AB - Fyn-deficient mice were produced by inserting the beta-galactosidase gene (lacZ) into the fyn gene locus. The homozygously Fyn kinase-deficient (fynz/fynz) mice exhibited stronger light aversion in the light-dark choice test and higher fear response scores in the novelty preference and passive avoidance tests than did the heterozygously Fyn-deficient (+/fynz) mice. These results indicate that fynz/fynz mice are hyperresponsive to fear-inducing stimuli. PMID- 7877450 TI - Cloning and expression of a human large-conductance calcium-activated potassium channel. AB - A putative BK channel gene was cloned from a human brain (substantia nigra) cDNA library by hybridization screening. The sequence of the full length clone shows high homology with the mSlo gene, suggesting that this cDNA is the human homologue (hSlo). The hSlo clone does not contain either alternative exon A or B at its splice sites; and similar to mSlo, it has a long string of serines at its 5' end. Reverse transcription coupled with the PCR technique demonstrated the differences in expression of the isoforms among the CNS and the periphery. Expression of hSlo in Xenopus oocytes showed a family of outward currents, induced by step depolarizations, that were blocked by iberiotoxin and activated by the compound NS004, a known opener of native and cloned maxi-K channels. Single channel recordings of hSlo channels showed a high degree of voltage- and Ca(2+)-dependence, and an average single channel conductance of 285.9 pS. PMID- 7877451 TI - Localization of type I interleukin-1 receptor mRNA in the rat brain. AB - The distribution of type I interleukin-1 receptor (IL-1R1) mRNA in the rat brain was examined by in situ hybridization technique. IL-1R1 mRNA was expressed in several brain regions including the anterior olfactory nucleus, medial thalamic nucleus, posterior thalamic nucleus, basolateral amygdaloid nucleus, ventromedial hypothalamic nucleus, arcuate nucleus, median eminence, mesencephalic trigeminal nucleus, motor trigeminal nucleus, facial nucleus and Purkinje cells of the cerebellum. Furthermore, we identified neuronal expression of IL-1R1 mRNA using simultaneous detection (double in situ hybridization) of IL-1R1 mRNA with neuron specific enolase mRNA. In addition to the expression in neuronal cells, IL-1R1 mRNA was also expressed on the vascular walls and the epithelial cells of the choroid plexus and the ventricles. These findings suggest the possibility that IL 1 produces its multiple effects on the central nervous system through the actions not only on neuronal cells but also on endothelial and epithelial cells. PMID- 7877452 TI - Isolation of a novel cDNA encoding a putative membrane receptor with high homology to the cloned mu, delta, and kappa opioid receptors. AB - A rat brain cDNA library was screened for clones homologous to the recently cloned mouse delta-opioid receptor (DOR-1). Among the clones isolated was Hyp 8 1, a clone with a unique nucleotide sequence capable of encoding a putative protein which is 57-58% identical to the amino acid sequences of the cloned delta, mu and kappa opioid receptors, indicating a close relationship of Hyp 8-1 with the opioid receptor family. Several cDNAs representing possible splice variants of Hyp 8-1 were also isolated. Binding studies of COS-7 cells transfected with clone Hyp 8-1 failed to demonstrate specific binding with several 3H-opioid ligands. In situ hybridization studies indicate that the mRNA for Hyp 8-1 is distributed discretely throughout the rat brain, in an overall pattern which is different from that of several other G-protein-coupled seven transmembrane receptors. Thus, it is likely that the Hyp 8-1 cDNA encodes a novel peptide receptor. PMID- 7877453 TI - mRNA distribution of two isoforms of somatostatin receptor 2 (mSSTR2A and mSSTR2B) in mouse brain. AB - The primary gene transcript of the mouse somatostatin receptor 2 is alternatively spliced giving rise to two isoforms (mSSTR2A and mSSTR2B) which differ at the C terminus. Using reverse transcription polymerase chain reaction (RT-PCR), both mRNAs were found in the cortex, hippocampus, hypothalamus, striatum, mesencephalon, cerebellum, medulla oblongata, pituitary and in testis, however with different ratios between mSSTR2A and mSSTR2B, implicating a tissue-specific control of transcription and splicing. Among the analyzed tissues, cortex contained the highest amounts of mSSTR2A but only little mSSTR2B, whereas the pons/medulla oblongata expressed both isoforms to an equal extent. Northern blot analysis of these tissues revealed a single mRNA of about 2.4 kb using a mSSTR2A specific hybridization probe. No additional signal was seen using a probe which hybridizes to both mSSTR2A and mSSTR2B, suggesting that the two mRNAs may be nearly identical in length. In addition, in situ hybridization indicated that mSSTR2A is predominantly expressed in mouse brain, and mSSTR2B is never expressed independently from mSSTR2A. PMID- 7877454 TI - Gene expression of GLUT3 and GLUT1 glucose transporters in human brain tumors. AB - GLUT3 glucose transporter gene expression is confined to neurons, while GLUT1 gene expression is limited to endothelial cells in normal brain. Thus far, neither of the GLUT genes has been shown to be consistently expressed in glial cells in adult brain in vivo under normal conditions. However, GLUT gene expression may be aberrant in human brain glial tumors. The present investigation shows that the GLUT1 and GLUT3 transcripts are differentially expressed in a series of 20 human brain tumors. The GLUT1/actin mRNA ratio increased in parallel to the astrocytoma grade, compared to a control human brain cortex, although no change in this ratio was seen in 5 meningiomas. Immunoreactive GLUT1 protein was not detectable in human brain tumors, including high-grade gliomas. Both 4.2 or 2.7 kb GLUT3/actin mRNA ratios showed a linear correlation with the glioma grade (P < 0.025), and the GLUT3-immunoreactive protein was also expressed in high grade gliomas. These studies provide evidence for induction of GLUT1 and GLUT3 gene expression in malignant glial cells, and the mRNA levels correlate with the biologic aggressiveness of the tumor. The detection of immunoreactive GLUT3, but not GLUT1, in the high grade gliomas suggest the GLUT3 isoform may be the predominant glucose transporter in highly malignant glial cells of human brain. PMID- 7877455 TI - Mouse NGF promoter upstream sequences do not affect gene expression in mouse fibroblasts. AB - The expression of nerve growth factor (NGF) is tightly controlled in a tissue specific manner during development and in response to injury. In fibroblasts and in other cell types, expression of NGF is regulated at the transcriptional level. In order to elucidate the mechanism of this regulation, we have undertaken the analysis of the mouse NGF promoter in a mouse fibroblast cell line (LTA), using transient transfection of NGF promoter-human growth hormone (hGH) reporter gene plasmids. We find that sequences between +8bp and +120bp, containing an AP-1 site, confer increased levels of expression from the full length and truncated NGF promoters. When this region is deleted, a significant decrease in expression is observed from both the full length promoter and truncated versions thereof. A gradual increase in expression is observed with successive 5' deletions of both the AP-1 containing and AP-1 deleted promoters; this effect results from the juxtapositioning of adjacent plasmid sequences closer to the transcription initiation site and not from deletion of promoter sequences as was previously reported. When the NGF promoter is analyzed using a luciferase reporter plasmid, these 5' promoter deletions have no significant effect on reporter gene expression in fibroblasts. Thus, sequences downstream of the transcription start site influence NGF promoter activity in fibroblasts, but sequences upstream of the TATA box fail to affect promoter activity in these cells. PMID- 7877456 TI - Expression of type I and type II interleukin-1 receptors in mouse brain. AB - Although binding sites for IL-1 have been identified in the mouse brain, it is still unknown whether these binding sites correspond to the type I or type II IL 1 receptor. Quantitative autoradiography was used to confirm the presence of specific binding sites for radiolabelled recombinant human IL-1 alpha (125I-HuIL 1 alpha) in the brain of DBA/2 mice. IL-1 binding was highest in the dentate gyrus, consisting of a single class of high affinity binding sites with a Kd of 0.1 nM and a Bmax of 57 fmol/mg protein. A similar Kd of 0.2 nM was obtained using isolated membranes from the whole hippocampus, although the number of binding sites was lower (2 fmol/mg protein). Affinity cross-linking of 125I-Hu-IL 1 alpha to hippocampal membranes revealed the existence of two types of IL-1 receptor proteins, consistent with the sizes of the type I (85 kD) and type II (60 kD) IL-1 receptor. Oligonucleotide probes were then synthesized and used in RT-PCR followed by Southern blotting to show that the whole brain expresses transcripts for both the type I and type II IL-1 receptors. The murine neuroblastoma cell line, C1300, expresses type I rather than type II IL-1 receptor mRNA. The type I receptor protein can be identified by flow cytometry on the membrane of the C1300 neuronal cell line using indirect immunofluorescence with a rat anti-mouse type I IL-1 receptor MoAb. These data show that mouse brain expresses both type I and type II IL-1 receptor mRNA and proteins and offer further support to the idea that type I IL-1 receptors are synthesized and expressed by neurons. PMID- 7877457 TI - Differential regional and time course increases in thyrotropin-releasing hormone, neuropeptide Y and enkephalin mRNAs following an amygdala kindled seizure. AB - Previous studies have shown that neuropeptide mRNA expression is altered in the dentate gyrus, and pyriform, entorhinal and perirhinal cortices following amygdala kindling. However, because rats were kindled every day and some mRNA alterations last longer than 24 h, a true measure of the alterations induced by a single seizure was confounded by the previous day's seizure. To circumvent this problem, rats were fully kindled, had six days without stimulation, and then were given one more seizure. Rats were sacrificed either 4 h, 24 h or 4 days after this last seizure. The levels of mRNAs for TRH, NPY and ENK were measured in the dentate gyrus and limbic cortices. Four hours after a seizure, TRH and NPY mRNAs were maximally increased in the dentate gyrus granule layer, but returned to baseline levels by 24 h. In contrast, 4 h after a seizure, TRH and NPY mRNAs were not, or only slightly, increased in the pyriform, entorhinal and perirhinal cortices, but significantly elevated 24 h after a seizure. ENK mRNA was increased both 4 and 24 h after a seizure in the pyriform, entorhinal and perirhinal cortices but showed no increases in the dentate gyrus at any time. By 4 days, peptide mRNA levels returned to baseline, except for ENK mRNA in the pyriform cortex. These results demonstrate a non-uniform and complex pattern of peptide mRNA expression following an amygdala kindled seizure. They further suggest that regional and time course differences in gene transcription and expression may be important factors in understanding both the transient, adaptive anticonvulsant and longer lasting proconvulsant effects of these neuropeptides. PMID- 7877459 TI - Regulation of VIP mRNA expression by thyroid hormone in different brain areas of adult rat. AB - A role of thyroid hormone in the regulation of neuropeptide synthesis has been demonstrated in different tissues. In this paper we investigated the vasoactive intestinal peptide (VIP) mRNA expression by means of in situ hybridization in several brain areas of hypo- and hyperthyroid adult rats. Neither hypo- nor hyperthyroidism modified the VIP mRNA levels in the thalamus and in the hypothalamic suprachiasmatic nucleus. In contrast, in the anterior cingulate and frontoparietal motor cortex of hypothyroid rats there was a marked increase in the signal for VIP mRNA per cell, but the number of VIP expressing neurons did not change. These data indicate that also central VIP synthesis can be influenced by the levels of circulating thyroid hormone, but that this effect is confined to specific areas and cell populations of the brain. PMID- 7877458 TI - Localization of phosphoneuroprotein 14 (PNP 14) and its mRNA expression in rat brain determined by immunocytochemistry and in situ hybridization. AB - Distribution and ultrastructural localization of a novel phosphoneuroprotein with a molecular mass of 14 kDa (PNP 14), and expression of its mRNA were studied in the adult rat central nervous system (CNS) by immunocytochemistry and in situ hybridization histochemistry. PNP 14 immunoreactivity was abundant in the molecular layer, present moderately in the granular layer, and rare in the Purkinje cell layer of the cerebellar cortex. No PNP 14 immunoreactivity was detected in the cerebellar medulla. In the forebrain, immunoreactivity was found in the hippocampus, striatum, and throughout the cerebral cortex, especially in layer V. Electron microscopic immunocytochemical observation in the cerebellar cortex revealed many PNP 14-immunoreactive axon terminals making synaptic contact with dendritic processes in both granular and molecular layers. PNP 14 immunoreactivity was present mainly in the cytoplasmic matrix in the presynaptic axon terminals. PNP 14 mRNA was localized in the granular layer of the cerebellar cortex, in the hippocampus, and in the cerebral cortex, suggesting that PNP 14 is synthesized in neurons of the granular layer and then transported to the molecular layer by axonal transport. These morphological findings suggest that PNP 14 is likely to modulate the function of selected CNS synapses. PMID- 7877460 TI - Ethanol and naloxone differentially upregulate delta opioid receptor gene expression in neuroblastoma hybrid (NG108-15) cells. AB - We have used a sensitive solution hybridization assay with a riboprobe transcribed from the coding sequence of the delta opioid receptor (DOR) to quantitate the changes in DOR mRNA transcript levels following exposure of NG108 15 cells to ethanol and/or the opioid antagonist, naloxone. Incubation of NG108 15 cells with 200 mM ethanol or 1 microM naloxone, treatments that have previously been shown to upregulate DOR binding, increased DOR mRNA transcript levels 2 to 3 fold. DOR mRNA levels peaked at 24 to 48 h after exposure to either ethanol or naloxone. At 168 h, DOR mRNA levels in NG108-15 cells exposed to naloxone had returned to control (untreated) levels while the levels in ethanol treated cells remained nearly equal to peak values. Exposure to a combination of ethanol plus naloxone for 24 h produced an additive effect, so that DOR mRNA transcripts were increased 3 fold. Northern blot analysis identified six DOR transcript bands ranging in size from 8.7 to 2.1 kb. The above treatments increased each of the six bands proportionately, so that no difference was observed in the fraction of the total hybridization signal produced by each band of the Northern blot. These results demonstrate that each of the DOR transcripts in NG108-15 cells are subject to homologous (naloxone) as well as heterologous (ethanol) upregulation. PMID- 7877461 TI - The effect of a racially consonant medical context on adjustment of African American patients to physical disability. AB - The effect of a racially consonant medical context on reaction to physical handicap stemming from disease is explored in a sample of 90 African-American patients with vitiligo, a disfiguring skin disorder. The adjustment of sixty-nine patients in a predominantly black hospital setting is compared to that of twenty one patients in a predominantly white hospital setting. The patients in the predominantly black clinic, where the physicians, staff, and clientele are African-American, show significantly better adjustment than do African-American patients in a medical context that is primarily white. Interviews with a random sample of one-third of the patients in each clinic show that patients are significantly more positive to black physicians and a black hospital setting and that other patients of the same race provide informal networks of support, as does the predominantly African-American community in which the hospital is located. Implications for both medical theory and practice are suggested on the basis of these findings. PMID- 7877462 TI - Attitudes toward HIV testing among impoverished inner-city African-American women. AB - During a study of the perceived benefits of unsafe (condomless) sex, some women's erroneous convictions that they have been tested for HIV seropositivity and most women's reluctance to identify their own sexual behaviors at high-risk when explaining why they had been tested were noted. Many participants assumed that clinicians drawing their blood would check it for HIV when they checked for other matter, and most of those reporting that they have had or would have HIV tests saw the test as part of a routine health check. Factors underlying the women's optimistically biased denial of their own HIV/AIDS risks and their related refiguring of the purposes and conditions of HIV testing are discussed, and the ways in which the women's attitudes critique current policies are described. Because of the culturally promoted strength and importance of women's denial, testing programs that seek to capitalize on an evoked sense of risk cannot succeed; such programs threaten women's faith in their relationships and question women's social and moral standings in a humiliating fashion. Those who promote testing would do better to present HIV screening as routine, because this is how women who accept testing generally portray it. Importantly, clinicians must explain that the test is not automatically administered. Cast as a standard health-related procedure for which permission must be granted, HIV testing will seem more rational, pro-active, and acceptable to the women targeted for testing. PMID- 7877463 TI - Loss and regeneration: influences on the reproductive decisions of HIV positive, drug-using women. AB - Current approaches to the reduction of perinatal transmission of HIV infection among drug-using women focus on the content of counseling sessions which may include suggestions to abstain from sexual intercourse, to use barrier contraceptives, or to terminate pregnancy. The broader social and cultural issues which may influence some HIV positive women's decisions to have children (such as prolonged, unwanted separation from existing children; the need for appropriate drug treatment; empowerment through educational and vocational opportunities; and the meanings associated with motherhood, children, and HIV/AIDS) are not addressed in these efforts. This study of the reproductive decisions and meanings associated with children and motherhood among drug-using, female methadone patients describes some of the social and cultural influences on reproductive decisions. The findings suggest that discontinuous mother-child coresidence; locally produced theories of perinatal transmission; and the culturally constructed meanings associated with motherhood and children influence decisions to bear children among HIV infected, drug-using women. Relevant policy issues are discussed. PMID- 7877464 TI - Negotiating sexual relationships after testing HIV-positive. AB - Drawing on in-depth interviews with 60 people with HIV disease and 40 of their caregivers, this article reports on the effects of HIV seropositivity on sexual interaction and relationship formation. Using a sample representing gay and heterosexual, black and white, and male and female respondents, we focus on how people in the syndrome account for, cope with, and work through problems associated with HIV. While disengagement from sexuality is common, at least initially, many respondents successfully readjusted the mutual understandings of ongoing relationships or went on to develop new ones, often with seronegative people. Further, we compare the experiences of those already in relationships when they test HIV-positive to those seeking new relationships and discuss problems of disclosure and safer sex, with notes on the responses and perceptions of HIV-negative sexual partners. PMID- 7877465 TI - Alcohol consumption and its effect on the dietary patterns of Hualapai Indian women. AB - Studies of Native American diet have ignored the nutritional and dietary effects of alcohol consumption. Studies of Native American alcohol consumption have largely ignored the socioeconomic characteristics and drinking behaviors of women. Seven-day 24-hour dietary recalls collected from 28 Hualapai Indian women revealed that 12 participants (43%) drank alcoholic beverages. Drinkers frequently skipped meals, yet maintained an energy intake higher than non drinkers by consuming high calorie alcoholic and non-alcoholic beverages and by eating large restaurant meals. Despite energy intake differences, drinkers and non-drinkers did not differ in body weight or percent body fat. Drinkers were not at risk for protein malnutrition as reported for other female drinkers, but Hualapais' tendency to fast while drinking may increase their risk of liver disease. In contrast to reports of Native American males, female drinkers in this sample were often high school graduates with full-time jobs. PMID- 7877466 TI - Reaching conclusions in forensic pathology. AB - Conclusions on the results of autopsy examination may be reached on the basis of experience, rather than by a formal process of reasoning. Suggestions are made for developing more precise processes of diagnosis by logical methods. PMID- 7877467 TI - Medical requirements and consequences of sex reassignment surgery. AB - Prior to considering surgical reassignment, the key issue for the surgeon is to establish beyond reasonable doubt that the gender dysphoria or transsexual feeling is genuine and that surgical reassignment will be beneficial. For this he will need the expertise of a reputable behavioural scientist. To determine whether the patient is physically fit for surgery, the surgeon may lean on the expertise of an endocrinologist with substantial personal experience in the field of hormonal treatment of transsexuals. Sex reassignment for M-->F transsexuals may be completed in one operation, leading to acceptable cosmetic and functional results, provided the surgery and postoperative treatment are performed with a high degree of expertise. Present generation operative techniques for phalloplasty in F-->M transsexuals still do not meet all requirements. The term 'one-stage phalloplasty' is deceiving. Genital reassignment surgery in F-->M transsexuals can seldom be achieved in one stage. Prior to any form of this kind of surgery, this should be made clear to the patient. F-->M and M-->F transsexuals will become irreversibly infertile by the orchiectomy and the oophoro-hysterectomy usually performed on them. Diagnosis of, and counselling and treatment for, gender dysphoria should be restricted to reputable gender teams. These teams should exchange information. PMID- 7877468 TI - Clinical language for expert witnesses. PMID- 7877469 TI - Ancillary autopsy--forensic histopathology and toxicology. AB - Under the Coroners Act 1988 and the Coroners Rules 1984, the removal of parts or contents of the body which does not bear directly upon the cause of death is restricted. However, it may not be possible in every forensic necropsy to foretell whether the post-mortem removal of body tissue will fulfil a statutory proviso. To emphasize this medico-legal predicament, some examples in which ancillary histopathological examination or toxicological analysis assisted in ascertaining an accurate cause and manner of death are presented as short cases. PMID- 7877470 TI - The Lund Lecture. PMID- 7877471 TI - Data modelization of individual variation in the calvaria. PMID- 7877472 TI - The use of legislation in cases of squalor. AB - In this paper, some of the legislation that can be used to treat people living in squalor is described. It can be used to enforce cleaning of the squalor for the individual or his/her neighbours' benefit. PMID- 7877473 TI - Medical confidentiality in sport and the public interest. PMID- 7877474 TI - Personality disorder and police section 136 in Westminster: a retrospective analysis of 65 assessments over six months. AB - Section 136 of the 1983 Mental Health Act empowers the police to detain those suspected of being mentally ill in public places. The current study is a retrospective analysis of those occurring within Westminster, London, over a six month period. A high rate of referral was found. In those individuals assessed, schizophrenia was the commonest diagnosis, but personality disorder provided the largest number of assessments. This was due to the propensity of the latter individuals to present on multiple occasions. Those with personality disorders were significantly less likely to be placed under further sections of the Mental Health Act, less likely to be admitted to hospital and more likely to re-present under a further section 136. The inability of the current system to address these individuals' needs is a cause for concern. PMID- 7877475 TI - Psychiatric in-patient violence: issues of English law and discipline within hospitals. AB - There has been a considerable increase in the number of publications about psychiatric patient violence, perhaps indicating an increase in violence or an increase in staff anxiety about assault. Missing from the debate are issues of law and ward discipline and these are discussed here. PMID- 7877476 TI - Sex differences in patients admitted to a regional secure unit. AB - The case notes of all admissions to a Regional Secure Unit over a 12-year period were examined. A higher proportion of females had a diagnosis of personality disorder. Women were less likely to have a prosecuted offence associated with admission but were more likely to be charged with fire-setting. Patients with personality disorder were more likely to be transferred to special hospitals. Women were nearly three times as likely as men to be transferred to maximum security and this was not accounted for by the excess of females with personality disorder. There was net movement of men out of special hospitals whereas the opposite was true for women. Possible explanations for this are discussed. PMID- 7877477 TI - Incidence of persons with a learning disability detained in police custody. A needs assessment for service development. AB - The aim of this prospective study was to identify the number of people with a possible learning disability suspected of having committed a criminal offence who were taken into police custody during a defined period of time. Between 18 January 1993 and 18 March 1993 992 people were taken into custody at Parkside Police Station, Cambridge, of whom 251 (25.3%) were screened by the custody officer using a brief questionnaire to ascertain the presence or absence of reading and writing difficulties and to see if they had received extra help at school or if they had attended a special needs school. Information on age, sex, suspected offence, disposal, if a solicitor assisted and incidence of homelessness was gathered from the custody reports. PMID- 7877478 TI - Laryngeal cyst and sudden death. AB - Laryngeal cysts are relatively uncommon and account for about five per cent of benign laryngeal lesions. The commonest location is the epiglottis. Pathologically these lesions may be divided into epithelial, tonsillar or oncocytic types. The patients may be asymptomatic or present with hoarseness, dysphagia, cough or airway obstruction. Epithelial cysts of the larynx, although histologically benign, may produce sudden and unexpected death from asphyxia. A case is presented of a 32-year-old female who was sexually assaulted and later found dead. Death was most likely due to laryngeal obstruction caused by an epiglottic cyst. Alcohol intoxication (BAC = 0.25g%) is likely to have been a contributory factor. In this case the results of the autopsy helped to exonerate the accused from being charged with murder. Other medico-legal problems that may be encountered with laryngeal cysts are difficulty in intubation and accidental rupture of a cyst during intubation or otolaryngeal examination. PMID- 7877479 TI - Sleeping foetus?--Medicolegal consideration of an incredibly prolonged gestational period. AB - In Libya, sexual intercourse between an unmarried couple is unlawful even if it was consensual. The defendant in this case pleaded not guilty to the charge despite the fact that she delivered a baby 29 months after divorce. She imputed paternity of the child to her ex-husband, who denied the allegation on the grounds of the extremely long gestational period. Her claim was that the baby was conceived three months prior to divorce, but had ceased to grow for some time. Her plea was based on the widely accepted notion amongst lay people, the so called 'sleeping foetus'. Following the medical opinion, the court dismissed the plea and the woman was convicted of unlawful sexual intercourse. PMID- 7877480 TI - Successful suicide by insulin injection in a non-diabetic. AB - We report the death of a young female non-diabetic after self-administration of insulin which led to the trial and conviction of her partner, who was himself an insulin-dependent diabetic. This brings out particular lessons for the pathologist in view of the rarity of such deaths, emphasizes the importance of careful laboratory analysis and illustrates a number of interesting legal points. PMID- 7877481 TI - Decapitation death. PMID- 7877482 TI - The coroner's court, the past, the present and the future. PMID- 7877483 TI - The use of the Appropriate Adult Scheme. PMID- 7877484 TI - Protein-based phylogenies support a chimeric origin for the eukaryotic genome. AB - The phylogenetic position of the archaebacteria and the place of eukaryotes in the history of life remain a question of debate. Recent studies based on some protein-sequence data have obtained unusual phylogenies for these organisms. We therefore collected the protein sequences that were available with representatives from each of the major forms of life: the gram-negative bacteria, gram-positive bacteria, archaebacteria, and eukaryotes. Monophyletic, unrooted phylogenies based on these sequence data show that seven of 24 proteins yield a significant gram-positive-archaebacteria clade/gram-negative-eukaryotic clade. The phylogenies for these seven proteins cannot be explained by the traditional three-way split of the eukaryotes, archaebacteria, and eubacteria. Nine of the 24 proteins yield the traditional gram-positive-gram-negative clade/archaebacteria eukaryotic clade. The remaining eight proteins give phylogenies that cannot be statistically distinguished. These results support the hypothesis of a chimeric origin for the eukaryotic cell nucleus formed from the fusion of an archaebacteria and a gram-negative bacteria. PMID- 7877485 TI - An anchored restriction-mapping approach applied to the genetic analysis of the Anopheles gambiae malaria vector complex 1. AB - We introduce here a simple approach for rapidly determining restriction maps for a number of regions of a genome; this involves "anchoring" a map with a rare restriction site (in this case the seldom-cutting EagI) followed by partial digestion of a frequent-cutting enzyme (e.g., Sau 3A). We applied this technology to five species of the Anopheles gambiae complex. In a single Southern blot we obtained about a 15-kb restriction map each for the mtDNA, rRNA gene, and a scnDNA region for each of five species. Phylogenetic analyses of these regions yield trees at odds with the more traditional chromosome inversion-based trees. The value of the approach for systematic purposes is the ease with which several large, independent regions of the genome can be quickly assayed for molecular variation. PMID- 7877486 TI - Nucleotide variation at the hypervariable esterase 6 isozyme locus of Drosophila simulans. AB - Esterase 6 (Est-6/EST6) is polymorphic in both Drosophila melanogaster and D. simulans for two common allozyme forms, as well as for several other less common variants. Parallel latitudinal clines in the frequencies of the common EST6-F and EST6-S allozymes in these species have previously been interpreted in terms of a shared amino acid polymorphism that distinguishes the two variants and is subject to selection. Here we compare the sequences of four D. simulans Est-6 isolates and show that overall estimates of nucleotide heterozygosity in both coding and 5' flanking regions are more than threefold higher than those obtained previously for this gene in D. melanogaster. Nevertheless, the ratio of replacement to exon silent-site polymorphism in D. simulans is less than the ratio of replacement to silent divergence between D. simulans and D. melanogaster, which could be the result of increased efficiency of selection against replacement polymorphisms in D. simulans or to divergent selection between the two species. We also find that the amino acid polymorphisms separating EST6-F and EST6-S in D. simulans are not the same as those that separate these allozymes in D. melanogaster, implying that the shared clines do not reflect shared molecular targets for selection. All comparisons within and between the two species reveal a remarkable paucity of variation in a stretch of nearly 400 bp immediately 5' of the gene, indicative of strong selective constraint to retain essential aspects of Est-6 promoter function. PMID- 7877487 TI - Functional constraints against variations on molecules from the tissue level: slowly evolving brain-specific genes demonstrated by protein kinase and immunoglobulin supergene families. AB - In the protein kinase family, the basic function of kinase domain is similar among members. According to the standard view of functional constraint, the molecular evolutionary rate depends on functional and structural features characteristic of individual molecules (local constraint). Thus the evolutionary rate of the kinase domain is expected to be similar for different members. Contrary to this expectation, a comparison of the evolutionary rates revealed a wide difference among members; it amounts to about 100 times difference between the maximum and minimum rates. A similar result was also found in members of the immunoglobulin (Ig) family. In addition, significant correlations in evolutionary rate were observed between the kinase domain and the Ig-like domain in the receptor protein tyrosine kinases and between the kinase domain and the SH domain in the nonreceptor-type kinases. Furthermore, the evolutionary rates of family members that are expressed tissue specifically differ widely, depending on their tissue distribution: members expressed in the brain evolve with significantly slower rates than those expressed in the immune system. These results strongly suggest the presence of an alternative constraint (global constraint) against changes on molecules derived from higher levels like tissues or organs. PMID- 7877489 TI - Success of maximum likelihood phylogeny inference in the four-taxon case. AB - We used simulated data to investigate a number of properties of maximum likelihood (ML) phylogenetic tree estimation for the case of four taxa. Simulated data were generated under a broad range of conditions, including wide variation in branch lengths, differences in the ratio of transition and transversion substitutions, and the absence of presence of gamma-distributed site-to-site rate variation. Data were analyzed in the ML framework with two different substitution models, and we compared the ability of the two models to reconstruct the correct topology. Although both models were inconsistent for some branch-length combinations in the presence of site-to-site variation, the models were efficient predictors of topology under most simulation conditions. We also examined the performance of the likelihood ratio (LR) test for significant positive interior branch length. This test was found to be misleading under many simulation conditions, rejecting too often under some simulation conditions. Under the null hypothesis of zero length internal branch, LR statistics are assumed to be asymptotically distributed chi 2(1); with limited data, the distribution of LR statistics under the null hypothesis varies from chi 2(1). PMID- 7877488 TI - Tests of applicability of several substitution models for DNA sequence data. AB - Using linear invariants for various models of nucleotide substitution, we developed test statistics for examining the applicability of a specific model to a given dataset in phylogenetic inference. The models examined are those developed by Jukes and Cantor (1969), Kimura (1980), Tajima and Nei (1984), Hasegawa et al. (1985), Tamura (1992), Tamura and Nei (1993), and a new model called the eight-parameter model. The first six models are special cases of the last model. The test statistics developed are independent of evolutionary time and phylogeny, although the variances of the statistics contain phylogenetic information. Therefore, these statistics can be used before a phylogenetic tree is estimated. Our objective is to find the simplest model that is applicable to a given dataset, keeping in mind that a simple model usually gives an estimate of evolutionary distance (number of nucleotide substitutions per site) with a smaller variance than a complicated model when the simple model is correct. We have also developed a statistical test of the homogeneity of nucleotide frequencies of a sample of several sequences that takes into account possible phylogenetic correlations. This test is used to examine the stationarity in time of the base frequencies in the sample. For Hasegawa et al.'s and the eight parameter models, analytical formulas for estimating evolutionary distances are presented. Application of the above tests to several sets of real data has shown that the assumption of stationarity of base composition is usually acceptable when the sequences studied are closely related but otherwise it is rejected. Similarly, the simple models of nucleotide substitution are almost always rejected when actual genes are distantly related and/or the total number of nucleotides examined is large. PMID- 7877490 TI - Assessing horizontal transfer of nifHDK genes in eubacteria: nucleotide sequence of nifK from Frankia strain HFPCcI3. AB - The structural genes for nitrogenase, nifK, nifD, and nifH, are crucial for nitrogen fixation. Previous phylogenetic analysis of the amino acid sequence of nifH suggested that this gene had been horizontally transferred from a proteobacterium to the gram-positive/cyanobacterial clade, although the confounding effects of paralogous comparisons made interpretation of the data difficult. An additional test of nif gene horizontal transfer using nifD was made, but the NifD phylogeny lacked resolution. Here nif gene phylogeny is addressed with a phylogenetic analysis of a third and longer nif gene, nifK. As part of the study, the nifK gene of the key taxon Frankia was sequenced. Parsimony and some distance analyses of the nifK amino acid sequences provide support for vertical descent of nifK, but other distance trees provide support for the lateral transfer of the gene. Bootstrap support was found for both hypotheses in all trees; the nifK data do not definitively favor one or the other hypothesis. A parsimony analysis of NifH provides support for horizontal transfer in accord with previous reports, although bootstrap analysis also shows some support for vertical descent of the orthologous nifH genes. A wider sampling of taxa and more sophisticated methods of phylogenetic inference are needed to understand the evolution of nif genes. The nif genes may also be powerful phylogenetic tools. If nifK evolved by vertical descent, it provides strong evidence that the cyanobacteria and proteobacteria are sister groups to the exclusion of the firmicutes, whereas 16S rRNA sequences are unable to resolve the relationships of these three major eubacterial lineages. PMID- 7877491 TI - Four-cluster analysis: a simple method to test phylogenetic hypotheses. AB - A simple statistical test for comparing three alternative phylogenetic hypotheses for four monophyletic groups is presented. This test is based on the minimum evolution principle, and it does not require any information regarding the branching order within each monophyletic group. It is computationally efficient and can be easily extended to five or more monophyletic groups. PMID- 7877492 TI - Monophyly of the order Rodentia inferred from mitochondrial DNA sequences of the genes for 12S rRNA, 16S rRNA, and tRNA-valine. AB - A recent analysis of amino acid sequence data (Graur et al.) suggested that the mammalian order Rodentia is polyphyletic, in contrast to most morphological data, which support rodent monophyly. At issue is whether the hystricognath rodents, such as the guinea pig, represent an independent evolutionary lineage within mammals, separate from the sciurognath rodents. To resolve this problem, we sequenced a region (2,645 bp) of the mitochondrial genome of the guinea pig containing the complete 12S ribosomal RNA, 16S ribosomal RNA, and transfer RNA(VAL) genes for comparison with the available sciurognath and other mammalian sequences. Several methods of analysis and statistical tests of the data all show strong support for rodent monophyly (91%-98% bootstrap probability, or BP). Calibration with the mammalian fossil record suggests a Cretaceous date (107 mya) for the divergence of sciurognaths and hystricognaths. An older date (38 mya) for the controversial Mus-Rattus divergence also is supported by these data. Our neighbor-joining analyses of all available sequence data (25 genes) confirm that some individual genes support rodent polyphyly but that tandem analysis of all data does not. We propose that the conflicting results are due to several compounding factors. The unique biochemical properties of some hystricognath metabolic proteins, largely responsible for generating this controversy, may have a single explanation: a cascade effect resulting from inactivation of the zinc binding abilities of insulin. After excluding six genes possibly affected by insulin inactivation, analyses of all available sequence data (7,117 nucleotide sites, 3,099 amino acid sites) resulted in strong support for rodent monophyly (94% BP for DNA sequences, 90% for protein sequences), which lends support to the insulin-cascade hypothesis. PMID- 7877493 TI - Phylogeny of whales: dependence of the inference on species sampling. PMID- 7877494 TI - The genomic rate of transposable element movement in Drosophila melanogaster. PMID- 7877495 TI - Use of spectral analysis to test hypotheses on the origin of pinnipeds. AB - The evolutionary origin of the pinnipeds (seals, sea lions, and walruses) is still uncertain. Most authors support a hypothesis of a monophyletic origin of the pinnipeds from a caniform carnivore. A minority view suggests a diphyletic origin with true seals being related to the mustelids (otters and ferrets). The phylogenetic relationships of the walrus to other pinniped and carnivore families are also still particularly problematic. Here we examined the relative support for mono- and diphyletic hypotheses using DNA sequence data from the mitochondrial small subunit (12S) rRNA and cytochrome b genes. We first analyzed a small group of taxa representing the three pinniped families (Phocidae, Otariidae, and Odobenidae) and caniform carnivore families thought to be related to them. We inferred phylogenetic reconstructions from DNA sequence data using standard parsimony and neighbor-joining algorithms for phylogenetic inference as well as a new method called spectral analysis (Hendy and Penny) in which phylogenetic information is displayed independently of any selected tree. We identified and compensated for potential sources of error known to lead to selection of incorrect phylogenetic trees. These include sampling error, unequal evolutionary rates on lineages, unequal nucleotide composition among lineages, unequal rates of change at different sites, and inappropriate tree selection criteria. To correct for these errors, we performed additional transformations of the observed substitution patterns in the sequence data, applied more stringent structural constraints to the analyses, and included several additional taxa to help resolve long, unbranched lineages in the tree. We find that there is strong support for a monophyletic origin of the pinnipeds from within the caniform carnivores, close to the bear/raccoon/panda radiation. Evidence for a diphyletic origin was very weak and can be partially attributed to unequal nucleotide compositions among the taxa analyzed. Subsequently, there is slightly more evidence for grouping the walrus with the eared seals versus the true seals. A more conservative interpretation, however, is that the walrus is an early, but not the first, independent divergence from the common pinniped ancestor. PMID- 7877496 TI - Amino acid replacements and wavelength absorption of visual pigments in vertebrates. AB - An important unanswered question in phototransduction is how visual pigments (VPs) regulate their wavelength of maximal absorption (lambda max). By constructing the evolutionary tree for 28 opsins with known lambda max values, we can identify the times and directions of lambda max shift of different VPs. A total of 55 amino acid changes are shown to correlate with the directions of lambda max shift and might have been important in determining lambda max of a VP. Among these, three amino acid changes are already proven to be responsible in modifying the green-sensitive VP to the red-sensitive VP. The present evolutionary analysis opens a new direction in understanding the mechanism for the regulation of wavelength absorption by a VP and, more generally, in studying molecular mechanism involved in adaptive evolution. PMID- 7877497 TI - Horizontal transmission, vertical inactivation, and stochastic loss of mariner like transposable elements. AB - Horizontal transmission has been well documented as a major mechanism for the dissemination of mariner-like elements (MLEs) among species. Less well understood are mechanisms that limit vertical transmission of MLEs resulting in the "spotty" or discontinuous distribution observed in closely related species. In this article we present evidence that the genome of the common ancestor of the melanogaster species subgroup of Drosophila contained an MLE related to the mellifera (honey bee) subfamily. Horizontal transmission, approximately 3-10 MYA, is strongly suggested by the observation that the sequence of the MLE in Drosophila erecta is 97% identical in nucleotide sequence with that of an MLE in the cat flea, Ctenocephalides felis. The D. erecta MLE has a spotty distribution among species in the melanogaster subgroup. The element has a high copy number in D. erecta and D. orena, a moderate copy number in D. teissieri and D. yakuba, and was apparently lost ("stochastic loss") in the lineage leading to D. melanogaster, D. simulans, D. mauritiana, and D. sechellia. In D. erecta, most copies are concentrated in the heterochromatin. Two copies from D. erecta, denoted De12 and De19, were cloned and sequenced, and they appear to be nonfunctional ("vertical inactivation"). It therefore appears that the predominant mode of MLE evolution is vertical inactivation and stochastic loss balanced against occasional reinvasion of lineages by horizontal transmission. PMID- 7877498 TI - L1 (LINE-1) retrotransposable elements provide a "fossil" record of the phylogenetic history of murid rodents. AB - The single most difficult problem in phylogenetic analysis is deciding whether a shared taxonomic character is due to common ancestry or one that appeared independently due to convergence, parallelism, or reversion to an ancestral state. Mammalian L1 retrotransposons undergo periodic amplifications in which multiple copies of the elements are interspersed in the genome. Because these elements apparently are transmitted only by inheritance and are retained in the genome, a shared L1 amplification event can only be an inherited ancestral character. We propose that L1 amplification events can be an excellent tool for analyzing mammalian evolution and demonstrate here how we addressed several refractory problems in rodent systematics using L1 DNA as a taxonomic character. PMID- 7877500 TI - Evolution of immunoglobulin VH pseudogenes in chickens. AB - In chickens, there is a single functional gene (VH1) coding for the heavy chain variable region of immunoglobulins, and immunoglobulin diversity is generated by gene conversion of the VH1 gene by many variable region pseudogenes (psi VH's) that exist on the 5' side of the VH1 gene. To understand the evolution of this unique genetic system, we conducted statistical analyses of VH1 and psi VH genes together with functional VH genes from other higher vertebrate species. The results indicate, first, that chicken VH genes are all closely related to one another and were derived relatively recently from an ancestral gene belonging to one of the three major groups of VH genes in higher vertebrates. Second, the rate of nonsynonymous substitution is slightly higher than that of synonymous substitution in the complementarity-determining regions (CDRs), which suggests that diversity-enhancing selection has operated in the CDRs even for pseudogenes. However, both the rates of synonymous and nonsynonymous substitution are higher in the CDRs than in the framework regions (FRs), apparently because of an interaction between positive selection and meiotic gene conversion in the CDRs. Third, a dot matrix analysis of the psi VH genes and genomic diversity (D) genes has indicated that the 3' end of psi VH genes is attached by D-gene-like sequences, and this region of psi VH genes has high similarity with D gene sequences. This suggests that V and D genes were fused at some point of evolutionary time and this fused element multiplied by gene duplication. Finally, two alternative hypotheses of explaining the evolution of the chicken VH gene system are presented. PMID- 7877499 TI - Analysis of copia sequence variation within and between Drosophila species. AB - The sequences of the 5' long-terminal repeat (LTR) and adjacent leader regions of 27 full-length copia elements isolated from natural populations of Drosophila melanogaster, D. simulans, and D. mauritiana are presented. Phylogenetic analyses indicate that although D. melanogaster copia elements are distinct from those of D. simulans and D. mauritiana, the elements of these latter two species are not distinguishable from one another. LTRs and adjacent 5' leader regions of elements isolated from D. simulans and D. mauritiana are structurally similar to one another and carry substantial deletional variation mapping to regions previously identified as being of potential importance for copia expression. PMID- 7877501 TI - Isolation and analysis of somatic cell mutants with defects in endocytic traffic. PMID- 7877502 TI - Rapid determination of cellular resistance-related drug efflux in tumor cells. PMID- 7877503 TI - Interactive data analysis for evaluation of B-cell neoplasia by flow cytometry. PMID- 7877504 TI - Strategies for rare cell detection and isolation. PMID- 7877505 TI - High-speed photodamage cell sorting: an evaluation of the ZAPPER prototype. PMID- 7877506 TI - Contributions of flow cytometry to studies with multicell spheroids. PMID- 7877507 TI - Functional measurements using HL-60 cells. PMID- 7877508 TI - Flow cytometry and sorting of plant protoplasts and cells. PMID- 7877509 TI - Use of fluorescence-activated cell sorting for rapid isolation of insect cells harboring recombinant baculovirus. PMID- 7877510 TI - Flow microsphere immunoassay for the quantitative and simultaneous detection of multiple soluble analytes. PMID- 7877512 TI - Standardization for flow cytometry. PMID- 7877511 TI - Calibration of flow cytometer detector systems. PMID- 7877513 TI - Primed in situ labeling (PRINS) and fluorescence in situ hybridization (FISH). PMID- 7877514 TI - Molecular phenotyping by flow cytometry. PMID- 7877515 TI - Psychological well-being, mid-life and the menopause. AB - Few studies of women's health in the menopausal years have formally assessed well being. The present study aimed to determine whether well-being during mid-life related to menopausal status, social circumstance, health status, interpersonal stress, attitudes and lifestyle behaviours. A random sample of 2000 Melbourne women aged 45-55 years were sought by random digital telephone dialling. A response rate of 70.6% was achieved. Interviews conducted on the telephone included a well-being scale--the Affectometer 2. The final data set, comprising 1503 individuals, was subjected to analyses of variance. Menopausal status did not significantly affect well-being. Well-being was found to be significantly related to current health status variables of general psychosomatic symptoms, general respiratory symptoms, history of premenstrual complaints, overall health assessment and interpersonal stress. Attitudes to ageing and to menopause were also significantly related to well-being scores. Lifestyle behaviors of smoking, exercise and marital status were also significantly related to well-being. Thus well-being of urban Australian-born, mid-aged women was related to current health status, psychosocial and lifestyle variables rather than to endocrine changes of the menopause. PMID- 7877516 TI - Intentions to use hormone replacement therapy in a community sample of 45-year old women. AB - A sample of 45-year-old women from 5 general practices in South London were asked about their intentions to use hormone replacement therapy by postal questionnaire. One hundred and six women (60%) responded. Ninety women who were not taking HRT formed the study sample. Over 80% expressed an opinion when asked about future HRT use. Forty-four percent expressed an intention to use HRT, 42% expressed an intention not to, and 13% expressed a lack of knowledge on which to base a decision. Reasons given by intenders were based on general hopes to 'feel better' among others. Non-intenders gave reasons reflecting disinclination to use drugs and to interfere with a normal process, as well as concerns about side effects. The characteristics of intenders and non-intenders were compared. There were no significant differences between groups in socio-demographic variables, or in general and gynaecological health factors. However, HRT intenders reported significantly lower self-esteem, higher levels of depressed mood, anxiety, and negative attitudes to the menopause. They also expressed stronger beliefs in their doctors' ability-as opposed to their own- to control their menopause experience. These results suggest that some women might be seeking HRT at menopause to help alleviate pre-existing emotional difficulties and this may have important implications for treatment adherence. PMID- 7877517 TI - Treatment of skin ageing symptoms in perimenopausal females with estrogen compounds. A pilot study. AB - A wide range of somatic symptoms of the perimenopausal female is due to the decrease of estrogen at that age. Minor attention has been paid hitherto to the involvement of estrogens in female skin ageing symptoms. In our study, the ageing skin of the face of perimenopausal females was treated with a 0.3% estriol cream (8 patients) or with a 0.01% estradiol cream (10 patients) for 6 months. Dermatologic follow-up was performed monthly. At each follow-up venous blood for radioimmuno assay determination of prolactin (PRL), follicle stimulating hormone (FSH) and estradiol (E2) was sampled. In addition, prior to and after 3 and 6 months of treatment, gynecological examinations for climacteric symptoms, mammary and colposcopic investigations and vaginal smears for cytology were performed. Both treatment groups showed improvement of the various skin ageing symptoms at the end of treatment. The effects of the group treated with topical estriol were slightly superior with regard to their extent and onset. No hormonal side effects were noted either clinically or by hormone monitoring. According to these preliminary results, local estrogen treatment appears to be a promising new approach for the treatment of skin ageing in perimenopausal females. However, for minimizing the risk of systemic hormonal side effects, concentrations and size of application field should be limited. PMID- 7877518 TI - Acceptability and skin reactions to transdermal estrogen replacement therapy in relation to climate. AB - The acceptability and skin reaction of Estraderm Transdermal Therapeutic Systems as a function of climatic variability were examined in various zones which alter considerably in their temperature and humidity. An open, noncomparative prospective study was carried out in four institutional out-patient menopausal clinics in varying climatic areas. Eighty symptomatic postmenopausal patients without previous estrogen replacement were examined. Estraderm T.T.S. 50 was applied twice weekly in four weekly cycles. Norethisterone-acetate tablets (1 mg), were taken orally for 12 consecutive days. Using a questionnaire, the subjects were asked about the efficacy of the treatment on postmenopausal symptoms, the adhesiveness and tolerability. The results were matched with the meteorological conditions. The duration of the study was 6 months. Acceptability of Estraderm T.T.S. is high (78.7%). Discontinuation of treatment was found in 21.3% of the study group. The main reason for discontinuation is due to skin reactions which occurred in 14 of the 80 patients (17.5%). Meteorological conditions in this study did not influence the rate of skin reactions. No difference in acceptability of the treatment was found in relation to the mean temperature and mean humidity as registered in the dry desert and the humid coastal areas. PMID- 7877519 TI - The effect of oestrogen and progestogen replacement therapy on systolic flow velocity in healthy postmenopausal women. AB - The effects on left ventricular systolic outflow velocity of 3 months' treatment with either continuous transdermal oestradiol or cyclical transdermal oestradiol with medroxyprogesterone acetate were assessed in 34 healthy postmenopausal women. Cardiac flow was measured by pulsed wave Doppler echocardiography in 14 of these women and by continuous wave Doppler echocardiography in 20. Control studies were made in ten premenopausal women using pulse wave Doppler and in ten with continuous wave Doppler. The indicators assessed were: ejection fraction (EF), preejection time (PEP), ejection time (ET), peak systolic flow velocity over the aortic valve (PFV), acceleration time (AT), flow velocity integral (FVI) and mean acceleration (MA). Postmenopausal women had significantly lower EF, PFV, FVI, MA but longer AT and ET compared to premenopausal women. After 3 months' transdermal oestradiol significant increases in EF, PFV, FVI and MA were observed whilst AT decreased. The response in all cardiac flow indicators was similar with added progestogen. Blood pressure, however, increased after the addition of progestogen. Nevertheless the addition of progestogen does not attenuate the effect of oestrogen therapy on left ventricular systolic flow velocity. PMID- 7877521 TI - Bioelectric signals in neurons structures and the Josephson effect. AB - In a series of experiments, a zero damped oscillating and rotating pendulum held in a human hand is identified as a source of geomagnetic field modulation. Its rotating periodical movement is believed to result from feedback interaction with sensing systems of the human body. Such a pendulum features extraordinary sensitivity and periodical responses are typical for sensors based on the Josephson effect. Experimentally measured functional relations of signals in neuron structures of living organisms are directly compared with typical signals occurring in superconductive structures with Josephson junctions. Basic properties of Josephson elements (e.g. the quantization of magnetic flux in SQUID sensors) which are directly linked to impulse signals measured in some network structures containing Josephson junctions are then analyzed. Referring to time response measures on neuron cells and comparing it to Josephson element characteristics, its highly analogous behaviour is emphasized and reasons for hysteresis of heat and cold sensors are explained. A complete set of topological parameters needed for establishing conditions that bring about quantum coherence phenomena in biological structures is introduced. Additional studies and trends for future neurophysical research in this field are recommended. PMID- 7877522 TI - Thalamic neuron theory: theoretical basis for the role played by the central nervous system (CNS) in the causes and cures of all diseases. AB - The Thalamic Neuron Theory (TNT) postulates that the central nervous system (CNS) is involved in all disease processes, as the CNS not only processes incoming physical and chemical information from the periphery, it also sends out physiological commands to the periphery in order to maintain homeostasis for the entire body. Inherent in its capacity to learn and adapt (i.e. to habituate) is the CNS' ability to learn to be sick (pathological habituation) by looking in certain deranged central neural circuitries, leading to chronic disease states. These pathologically habituated states can be reversed by dehabituation through manipulation or modulation of the abnormal neural circuits by physical means (physical neuromodulation) like acupuncture, or chemical means (chemoneuromodulation) such as Chinese medicine, homeopathy or other modern medical techniques in a repetitious manner to mimic the habituation process. Chemoneuromodulation can also be achieved by delivery of minute amounts of pharmacological agents to specific sites in the periphery such as the acupuncture loci. It is hypothesized that humoral and neurotrophic factors and cytokines could be highly effective neuromodulating agents. TNT assumes the blue print for embryological development is embodied in the phylogenetically ancient part of the brain. This primordial master plan, organized in the form of a homunculus, possibly encased in a small nucleus, retains control over the subsequently evolved parts of the brain so that the entire CNS functions like a composite homunculus which controls the physiological functions of the entire body. TNT further postulates that the master homunculus takes the shape of a curled up embryo with its large head buried close to its pelvic region, with its large feet and hands crossed over to the contralateral sides. Neuronal clusters along a neuronal chain in the homunculus represent acupuncture points in the periphery. The neuronal chain itself represents a meridian and Chi is nothing more than the phenomenon of neurotransmissions. Certain new theoretical concepts such as the principles of Adynamic Stat and Bilaterality are also presented. Many difficult to explain clinical observations in modern medicine, Chinese herbal medicine, acupuncture and homeopathy can now be adequately explained using TNT. Based on this model, new therapeutic techniques can be launched to combat a whole host of intractable diseases. PMID- 7877520 TI - Pituitary down-regulation with a single depot-dose of a GnRH agonist (triptorelin) in postmenopausal women. AB - Gonadotropin levels were determined in 17 postmenopausal women before and after administering a single depot-dose of the GnRH agonist triptorelin. E2 levels of all samples were in the normal (low) postmenopausal range and no differences were found when the patients were grouped according to chronological age, or time after menopause. Pre-GnRH agonist levels of LH and FSH were in the normal (high) postmenopausal range. Two weeks after medication, LH and FSH had decreased to premenopausal levels (P < 0.0001). Eight weeks after medication, LH levels were still low whereas FSH levels had risen significantly again (P < 0.0001). Both LH and FSH levels, however, were still significantly below the serum concentrations before the administration of triptorelin (P < 0.0001). The pre-GnRH agonist level of FSH was significantly higher in women > 67 years old (P < 0.05), as compared to women < 67 years. Two weeks after medication both LH and FSH levels were significantly higher in women more than 15 years after menopause (P < 0.05), as compared to those < 15 years. The same was found for FSH in women > 67 years old. No further significant differences were noted. This study demonstrates a significant decrease of LH and FSH serum levels in postmenopausal women within two weeks after administration of a single depot-dose of the GnRH agonist triptorelin. After eight weeks, in contrast to premenopausal women, both LH and FSH, although rising, were still significantly suppressed. PMID- 7877523 TI - Radiation-induced malignant melanoma: the dog that did not bark. AB - A history of exposure to ultraviolet rays, such as those in sunlight, has been strongly associated with malignant melanoma. Gamma rays consist of much more energetic photons, but yet they have much more tenuous links to melanoma. A literature review suggests that relatively little evidence has been adduced for gamma radiation as a cause of malignant melanoma. An exploration of the reasons behind the paradoxical lack of melanoma induction by gamma radiation may yield clues to the etiology of melanoma. PMID- 7877524 TI - A hypothetical mechanism for toxic cataract due to oxidative damage to the lens epithelial membrane. AB - Lenticular opacities can be induced by numerous external agents that coincide with those that catalyze oxidative damage to lipids. One of the consequences of lipid peroxidation is that the affected membrane is rendered more permeable to protons. A proton leak in the tight epithelium of lens would uncouple the Na+/K(+)-ATPases that regulate the water and ionic content of the bounded tissue. Once regulatory control of the osmotic pressure is lost, the phase state of the cell's soluble proteins would change, leading to refractive changes or, in extreme cases, precipitation. The same does not occur in cornea because the stroma is an extracellular polymer blend rather than solution of soluble polymers. Polymeric phase transitions in the cornea require that divalent cations pass the epithelial membrane, which can occur only through the action of ionophores. PMID- 7877525 TI - Segmental blood flow through intramyocardial coronary arteries during ventricular systole. AB - The presented hypothesis assumes, in contrast with the currently prevailing view, that blood continues to flow through the coronary vascular bed even during systole. The contraction of differently oriented myocardial layers closes the penetrating branches of the coronary arteries in the interlayer boundaries. Coronary arteries of a different caliber are during systole under equal intramyocardial pressure. In accordance with the theory of elasticity, the action of an equal external pressure decreases with the lumen of the vessel and, thus, the net effect of these forces will push the blood into smaller vessels within the segment in the layer. This hydrodynamic effect empties the larger coronary arteries during systole so that they are ready for the subsequent massive influx of blood during diastole. The possible applications of this hypothesis in various physiological and pathological conditions are compatible with the present knowledge and might contribute to a more precise understanding of implicated pathophysiological mechanisms. PMID- 7877526 TI - The role of cytokines in early detection of preeclampsia. AB - The signs and symptoms of preeclampsia become apparent at a relatively late stage in pregnancy (third trimester). However, the disorder results from abnormal interaction between fetal and maternal tissue much earlier in pregnancy (first trimester). For this reason, numerous methods have been proposed for the early detection of preeclampsia with considerable disagreement regarding their sensitivity and predictive values. Various reports suggest that preeclampsia is caused by an abnormal maternal immune response to antigenic challenge by the fetoplacental allograft. Moreover, since cytokines are involved in the control of immune response and also have a role in fetal development, their release from the placenta as a consequence of the abnormal maternal immune response, may precede the consequential cascade of pathophysiological reactions shown in preeclampsia. These assumptions may suggest that plasma cytokines' measurements may be used for the early detection of preeclampsia. PMID- 7877527 TI - Psychological influences in disease: a decision theory model. AB - The integrity of living organisms depends on analyzing information from an uncertain and hostile world and responding appropriately to it. Statistical decision theory indicates that an optimum decision strategy takes into account information, probability and subjective values ascribed to correct and incorrect responses. It follows that decisions at all levels, including the molecular level, can be strongly influenced by psychological and emotional states which influence subjective evaluation. This concept provides a framework within which psychological influences in disease can be analyzed. PMID- 7877528 TI - Multifactorial interactions in the aetiopathogenesis of EPH-Gestosis--a hypothesis. AB - The aetiopathogenesis of EPH-Gestosis or pre-eclampsia-eclampsia is still not clear. Although many hypotheses implicating environmental, nutritional, immunological, and genetic factors have been put forward, no hypothesis provides the scientific basis for the early spiral arterial degenerative changes, and incomplete physiological trophoblastic invasion of the spiral arteries, leading to a high utero-placental resistance with reduced blood flow remains unexplained. To get an insight into the basic pathogenesis of EPH-Gestosis, the following hypothesis has been proposed. The hypothesis considers an abnormal proliferation of the spiral vessels as the key factor in the pathogenesis of the high uteroplacental resistance and the endothelial dysfunctions in EPH-Gestosis. Further it is proposed that this proliferation is on account of the enhanced polymerization of the deficient DNA triggered by the high steroidal level and relatively low micronutrient level in EPH-Gestosis during the early formative stages of the placental circulation. Steroidal hormone helps in polymerization of the DNA, micronutrients exert a controlling influence through DNA synthesis on cell proliferation. A critical balance of hormone-micronutrients such as vitamin A, B12, folic acid, etc., therefore, seems necessary for normal cellular proliferation. It appears therefore that there probably exists an imbalance with a high estrogen and a relatively low micro-nutrient level in EPH-Gestosis, triggering off a process of abnormal spiral vessel proliferation. These abnormal vessels with a deranged endothelial function may prevent the second wave of normal trophoblastic invasion assumed to be important for the establishment of the low resistance uteroplacental circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877529 TI - 'Oil globules' in Duchenne muscular dystrophy--history, demonstration, and metabolic significance. AB - Duchenne, Meryon, Wernich, Clarke, Down and other dystrophy pioneers recognized, illustrated and/or described Duchenne muscular dystrophy skeletal muscle's 'oil globules'. Rarely mentioned or acknowledged since the introduction in 1869 by Klebs of paraffin embedding and modern histological technique (in which tissue lipids are eliminated) this microscopical marker of metabolic dysfunction is utilized to find its metabolic site of origin in the living cell, to identify the disease's major dysfunctioning metabolic pathway, and finally to determine its dystrophin connection which accounts for the primary metabolic malfunction and the clinical manifestations of disease. This paper presents a working hypothesis developed through a long-term empirical study and suggests a practical method of therapy. PMID- 7877530 TI - Arginine supplementation in the prevention and treatment of osteoporosis. AB - Oral administration of L-arginine in pharmacological doses induces growth hormone and insulin-like growth factor-I responses and stimulates nitric oxide synthesis. Growth hormone and insulin-like growth factor-I are important mediators of bone turnover and osteoblastic bone formation, while nitric oxide is a potent inhibitor of osteoclastic bone resorption. Because of this dual effect on physiological regulators of bone remodeling, L-arginine could potentially increase bone formation over bone resorption, and, consequently, increase bone mass. It is, therefore, hypothesized that oral supplementation of L-arginine may be a novel strategy in the prevention and treatment of osteoporosis. Studies of this simple, safe, and inexpensive therapy seem warranted. PMID- 7877531 TI - The etiology of intimal hyperplasia. AB - Injury of an arterial wall results in the growth of a neointima which can cause significant luminal narrowing. Current theories do not adequately explain the experimental and clinical data. We propose the hypothesis that some substance produced by the media is inhibitory to smooth muscle cell proliferation. This substance cannot cross the normal intima. Following an injury which removes the intima this substance quickly diffuses out of the arterial wall into the blood, its concentration in the arterial wall falls and proliferation of smooth muscle cells begins. Later, as the arterial wall volume increases and the lumen (and, thus, area for diffusion) decreases, the substance returns to inhibitory levels and intimal hyperplasia ceases. PMID- 7877532 TI - Man's emotional capacity--an unexplored and unexploited possibility. AB - Man's mental functions have developed unevenly. Sometime during the last millennium the muscle man was superseded by the intelligent man. The human psyche, besides intellectual capacity, includes a basic function that can be called emotional capacity. This function can be studied using the same approach as in the study of intellectual capacity. The two functions are considered to be partly independent of each other. Emotional capacity depends on the individual's genetic emotional make-up (emotional genotype) and how this inherited set of qualities has been conditioned by environmental factors (emotional phenotype). Man's emotional capacity is very little differentiated: emotionally, modern man still functions almost like Stone Age man. Intellectual capacity, however, has undergone enormous development. As emotional capacity to a large extent governs man's behaviour and intellectual capacity is the instrument he uses to reach his goals, the uneven differentiation of the mental functions may have consequences that are unfavourable to the survival of our species. PMID- 7877533 TI - Role of prolactin in dysmotility-like gastric dyspepsia. AB - The phylogenetic, therapeutic and experimental evidences suggest that the circulating prolactin levels alter the gastric contractility in experimental animals as well as in patients suffering from gastric dyspepsia. The dopamine antagonists are used in the treatment dysmotility-like dyspepsia and could relieve the dyspeptic symptoms. These drugs are potent stimulants for the release of prolactin. Further, in non-ulcer dyspepsia, a primary dysfunction of pituitary lactotrophs has been proposed. Thus, the dysmotility-like gastric dyspepsia is associated with the deficiency of endogenous prolactin levels so as to reduce gastric contractions. This concept brings a new line of thinking in the pathogenesis of dysmotility-like gastric dyspepsia. PMID- 7877534 TI - Detecting and treating early atherosclerosis. PMID- 7877535 TI - When should postmenopausal women start taking oestrogen replacement therapy? PMID- 7877536 TI - Prescription for poisoning. PMID- 7877537 TI - Epidemic gonococcal conjunctivitis in central Australia. AB - OBJECTIVES: To describe an epidemic of gonococcal conjunctivitis in central Australian Aboriginal children, the responsible phenotypes of Neisseria gonorrhoeae, factors facilitating spread and treatment efficacy. DESIGN: Prospective study of patients with laboratory confirmed or clinical gonococcal conjunctivitis diagnosed from January to July 1991. SETTING: The Alice Springs and Barkly Tablelands Health Districts of the Northern Territory, the Anangu Pitjantjatjara Lands of South Australia and the Ngaanyatjarra Homelands of Western Australia. METHODS: Cases were identified from surveillance data and laboratory notifications, and by active case finding. A community survey explored risk factors. MAIN OUTCOME MEASURES: Age-specific attack rates, auxotype/serovar characterisation of isolates, and clinical response to single dose treatment. RESULTS: We identified 432 cases. The highest attack rate was in the 0-4 year age group (86 per 1000), and the risk of conjunctivitis decreased with age. The odds ratio of secondary infection in household compared with community contacts was 14.5 (P < 0.002; 95% CI, 1.8-120.0). Disease was less common in children with clean faces and hands. The outbreak occurred after unseasonable rains and large community gatherings. Isolates were predominantly IA serovars, less common among central Australian serovars. CONCLUSIONS: The trigger for nonsexually transmitted gonococcal conjunctivitis epidemics remains obscure. Age is a significant risk factor and social and ecological factors may also contribute. Active case finding within affected households and treatment with a suitable penicillin is effective in stopping transmission. PMID- 7877538 TI - Invasive pneumococcal disease in central Australia. AB - OBJECTIVES: To document the incidence, case fatality, clinical and demographic features of invasive pneumococcal disease in central Australia. DESIGN: Invasive isolates from the regional central laboratory were prospectively recorded over five years and case notes retrospectively reviewed. Population denominators were calculated from national Census data from 1986 and 1991. RESULTS: The population estimates for the region were 14,568 for Aboriginals and 28,680 for non Aboriginals. There were 185 episodes of invasive pneumococcal disease over the five years, 162 (87.5%) in Aboriginals and 23 (12.5%), in non-Aboriginals. The incidence in Aboriginal children under two years of age was 2052.7 per 100,000 and for those 20-59 years was 178.2 per 100,000. The relative risk in Aboriginals compared with non-Aboriginals was 10.8 (95% CI, 5.6-20.7; P < 0.0001) for those aged 0-4 years and 20.4 (95% CI, 9.7-42.5; P < 0.0001) for those 15-59 years. Forty-one Aboriginal adults aged over 14 (62%) had at least one conventional risk factor for pneumococcal disease; alcohol abuse was present in 27 (41%). There were 13 Aboriginal deaths and the case fatality rose from 2% in those under four years to 40% for those over 59 years. CONCLUSIONS: Central Australian Aboriginals have the highest incidence of invasive pneumococcal disease reported. The rate for children under two years is 59 to 80 times the rates for children in the United States and Sweden. These data have implications for improving vaccine use, health service delivery and environmental health in Aboriginal communities. PMID- 7877539 TI - Maternal and neonatal outcome of patients classified according to the Australasian Society for the Study of Hypertension in Pregnancy Consensus Statement. AB - OBJECTIVE: To outline the maternal and perinatal features and outcome of patients referred to a tertiary referral obstetric hospital for management of their hypertension. SETTING AND PATIENTS: 205 consecutive public patients admitted for assessment of hypertension (either full admission or day-stay) to King George V Hospital's Hypertension in Pregnancy Unit, between February 1993 and January 1994. DESIGN: A prospective study in which patients were classified according to the Australasian Society for the Study of Hypertension in Pregnancy (ASSHP) Consensus Statement classification. RESULTS: Of the 205 patients, 25% did not meet the criteria for pre-eclampsia or chronic hypertension, 33% had mild pre eclampsia, 34% had severe pre-eclampsia and the remainder had chronic hypertension. The mean gestation at delivery for those with mild pre-eclampsia was 38.3 weeks and for severe pre-eclampsia 35.3 weeks. For the mild and severe groups respectively, the rate of elective delivery for raised blood pressure was 56% and 53%; for caesarean section, 17% and 61%; and for perinatal death, 2% and 4%. In the severe group, 49% had fetal problems and 25% required intravenous antihypertensives. CONCLUSIONS: The multisystem nature of pre-eclampsia makes comparison of management protocols difficult. Ongoing audit is needed of maternal and perinatal outcomes and features of disease in patients with hypertension in pregnancy under a universal classification. The ASSHP classification system successfully identifies patients who require more intensive management and intervention. PMID- 7877540 TI - Self-poisoning in Newcastle, 1987-1992. AB - OBJECTIVE: To examine the morbidity and mortality associated with self-poisoning with different drug classes. DESIGN: Prospective cohort study with limited follow up. Retrospective analysis of coronial data. SETTING: Primary and tertiary referral toxicology centre covering Newcastle and Lake Macquarie, Australia, 1987 1992. RESULTS: There were 1969 admissions after ingestion of 3724 substances (2424 prescription drugs and 1300 non-prescription items). The coroner investigated 83 drug-related deaths. Only 12 of these people presented to hospital and, for most of these, death was inevitable at presentation. The most frequently ingested substances were benzodiazepines, alcohol, paracetamol, antidepressants, neuroleptics and anticonvulsants. Since 1980, the percentage of self-poisonings involving benzodiazepines has fallen, while it has risen for those involving antidepressants. Over 50% of deaths were due to tricyclic antidepressants or opioid analgesics. CONCLUSIONS: As death usually occurs out of hospital, interventions to decrease mortality from self-poisoning must focus on prevention, and targeting drugs that are frequently taken or frequently lethal in overdose. Consideration should be given to the use of antidepressants that are safer in overdose. The use of antidepressants, barbiturates or chloral hydrate as sedatives should be discouraged. PMID- 7877542 TI - Systemic bacterial and fungal infections in infants in Australian neonatal units. Australian Study Group for Neonatal Infections. AB - OBJECTIVE: To examine the pattern and incidence of sepsis occurring in neonatal units in Australia. DESIGN: A one-year prospective study of babies with systemic sepsis within 48 hours of birth (early-onset sepsis) or after this time (late onset sepsis) in seven Australian neonatal units. Systemic sepsis was defined as clinical sepsis, plus either positive bacterial or fungal culture of blood and/or cerebrospinal fluid, or group B streptococcal antigen detected in the urine. RESULTS: There were 241 episodes of sepsis, affecting 234 babies. One quarter (61) were early-onset, a rate of 2.2 per 1000 live births. Group B streptococcus (GBS) was the commonest cause of early-onset sepsis, with a rate of 1.3 per 1000 live births. The incidence of early-onset GBS sepsis was lower at a hospital which screened for maternal carriage and used intrapartum antibiotic prophylaxis for all carriers. The rate of late-onset sepsis was 4.4 per 1000 live births and coagulase-negative staphylococci were the commonest cause. Meningitis occurred in 23% of babies with early-onset and in 10% with late-onset sepsis. The mortality from early-onset sepsis was 15%, and from late-onset sepsis was 9%. There were no major regional variations, other than for GBS. CONCLUSIONS: The incidence of and mortality from neonatal sepsis is comparable to other countries, and shows no major regional variation. The use of intrapartum antibiotics may reduce the incidence of neonatal GBS sepsis. There are no previous comparable data on neonatal infections in Australia. PMID- 7877541 TI - Correlations between prescriptions and drugs taken in self-poisoning. Implications for prescribers and drug regulation. AB - OBJECTIVE: To compare prescription data for Australia with drugs ingested in self poisoning and suicide, to determine which drugs are over-represented. DESIGN: Comparison of data on drugs taken in self-poisoning admissions and suicides with Australian prescription drug dispensing data from the Drug Utilization SubCommittee (DUSC). SETTING: Newcastle and Lake Macquarie, Australia, 1989-1992. SUBJECTS: Between July 1989 and June 1992, 1159 prescription drugs were taken in overdose. Eighty-three drug-related deaths were investigated by the coroner between 1987 and 1992. On 48 occasions a prescription drug was the primary cause of death. RESULTS: Drugs over-represented in self-poisoning (relative to Australian prescriptions) included not only those prescribed for psychiatric conditions (antidepressants, neuroleptics and lithium), but also benzodiazepines, barbiturates and other anticonvulsants. The highest odds ratios for death when adjusted for prescription numbers were for short-acting barbiturates (523.7; 95% confidence interval [CI], 207-1322), chloral hydrate (58.1; 95% CI, 18.1-187), colchicine (27.9; 95% CI, 3.8-202), dextropropoxyphene (20.8; 95% CI, 8.8-48.9), tricyclic antidepressants (13.3; 95% CI, 7.2-24.5) and anticonvulsants (11.6; 95% CI, 4.1-32.2). CONCLUSIONS: Short-acting barbiturates, chloral hydrate and dextropropoxyphene have little or no clinical advantage over alternatives and excessive toxicity in overdose. They should be removed from the market. The toxicity of anticonvulsants and colchicine should be considered when they are prescribed, and smaller amounts per prescription may be advisable for high risk patients using these and other toxic drugs. PMID- 7877543 TI - Day stay transcatheter radiofrequency ablation for supraventricular tachyarrhythmias. AB - OBJECTIVE: To describe our initial experience with transcatheter radiofrequency ablation as a day stay procedure for patients with supraventricular tachyarrhythmias resulting from aberrant atrioventricular pathways. DESIGN: Prospective study of the first 50 patients at the Royal Perth Hospital whom we intended to treat and discharge on the same day. Patients underwent a combined electrophysiological study and radiofrequency ablation. RESULTS: Accessory pathways were identified in 32 patients (successfully ablated in 30) and dual atrioventricular nodal pathways in 18 patients (with successful ablation of the slow pathway in 17). Thirty-eight patients were discharged on the same day (24 treated for accessory pathways, and 14 treated for dual atrioventricular nodal pathways). There were no late complications or readmissions in patients discharged on the same day. CONCLUSIONS: In patients with supraventricular tachyarrhythmia, day stay transcatheter ablation can be planned without a definitive prior diagnosis of the physiological cause. Complications or other reasons for overnight admission are apparent at completion of the procedure. PMID- 7877544 TI - Efficacy of pravastatin in combination with captopril in hypertensive patients. AB - OBJECTIVE: To determine the efficacy of pravastatin in the treatment of primary hypercholesterolaemia in patients being treated with captopril for hypertension. DESIGN: A double-blind parallel group study comparing 12 weeks of pravastatin therapy (20-40 mg/day) with placebo. PARTICIPANTS: 25 patients (age, 37-73 years) with mild-to-moderate hypertension and hypercholesterolaemia (total cholesterol level, 5.5-8.8 mmol/L). RESULTS: Pravastatin reduced total cholesterol levels by 22% (from 7.1 +/- 0.29 [SEM] to 5.5 +/- 0.25 mmol/L; P < 0.001) and low-density lipoprotein cholesterol levels by 32% (from 5.0 +/- 0.32 to 3.4 +/- 0.28 mmol/L; P < 0.001) in four weeks and these levels were maintained for the 12 weeks of therapy. Pre-pravastatin values returned three weeks after stopping therapy. Levels of total cholesterol, cholesterol fractions and triglycerides remained constant or deteriorated in the placebo group. Pravastatin therapy was well tolerated. An integrated coronary risk score showed a 40% reduction in risk. CONCLUSION: This study indicates that pravastatin (combined with captopril) is an effective cholesterol-lowering drug, but that treatment needs to be maintained. PMID- 7877545 TI - Infection associated with central venous catheters: a prospective survey. AB - OBJECTIVE: To assess the incidence of local and systemic infection caused by central venous catheters in a general hospital population. SETTING: Concord Repatriation General Hospital, Sydney, April to August 1991 inclusive. DESIGN: A prospective survey of all patients with in situ central venous catheters. Systemic catheter-related infection was detected by blood and routine catheter tip culture, and local infection by clinical observation of the catheter exit site. OUTCOME MEASURES: Local and systemic infection and complications. RESULTS: 479 central venous catheters were surveyed in 311 patients. Local infection developed in association with 54 catheters (11%) and systemic infection with 32 (6.7%). Local infection was predictive of systemic infection, but its absence did not exclude systemic infection. Haemodialysis catheters were responsible for a higher systemic infection rate than other catheter types, the most common organism responsible being methicillin-resistant Staphylococcus aureus. Twenty per cent of all bacteraemias (33/160) detected in the hospital occurred in patients with a central venous catheter and 24 of these (73%) were definitely or probably due to the catheter. Staphylococci were the predominant isolates and 40% of the methicillin-resistant S. aureus bacteraemias detected were due to catheter related infection. Infection complications were few: three patients developed local abscesses; one endocarditis; and two died. CONCLUSIONS: Central venous catheter-related infection is common in general hospital populations. Staphylococcal bacteraemia and local infection in a patient with a central venous catheter are strongly suggestive of catheter-related systemic infection. Empirical antibiotic treatment should include at least antistaphylococcal cover. PMID- 7877546 TI - Guillain-Barre syndrome complicating treatment with streptokinase. PMID- 7877547 TI - Lower gastrointestinal tract. 2. Diarrhoea and diverticular disease. AB - For more than 70% of patients with diarrhoea, investigation can reveal a cause, which should be treated specifically whenever possible. Symptomatic treatment can be a useful adjunct or a mainstay if no cause can be found. Drug selection and doses are similar to those for younger age groups, but drug interactions and side effects, and dose adjustment because of renal failure, are more likely in the elderly. PMID- 7877548 TI - False-negative results for HIV-1. PMID- 7877549 TI - Lipid management after coronary bypass surgery. PMID- 7877551 TI - A lesson in malaria prophylaxis from Cambodia. PMID- 7877550 TI - Mycobacterium ulcerans infection on Phillip Island, Victoria. PMID- 7877552 TI - Malaria acquired in Bali. PMID- 7877553 TI - Rotavirus and seizures. PMID- 7877554 TI - Bronchospasm after scuba diving. PMID- 7877555 TI - Lamotrigine for epilepsy. PMID- 7877556 TI - Pegaspargase for acute lymphoblastic leukemia. PMID- 7877557 TI - Portable prothrombin time monitors. PMID- 7877558 TI - The nature of the bone-implant interface. The lessons learned from implant retrieval and analysis in man and experimental animal. AB - The morphological appearances of the interface between the bone and the components of arthroplasties depend on multiple factors. Present-day biomaterials being biocompatible when in bulk form, a host reaction consequent upon untoward effects of the implants as such is not expected. Thus, osseointegration, i.e., the direct apposition of bone to the surface of a foreign material at the light microscopical level, occurs, under favorable biomechanical circumstances, irrespective of the chemical composition of the implant. Osseointegration is a multifaceted phenomenon. First and foremost, it evolves when an initially rigid fixation of the component is surgically attained. Interfacial motions are associated with resorption of the bony bed, macrophagic activation and production of wear particles, the close bone-implant apposition is lost and the formation of an interfacial membrane (IM) ensues. The histological features of the IM coincide with the context of its formation and evolution. The quiescent IM is composed of a thin layer of fibrous tissue and its occurrence is compatible with the biofunctionality of the implant. The aggressive or lytic IM (LIM) develops when tissue-irritating, small, irregularly shaped and edgy breakdown products are deposited at the interface. The thick LIM consists of an inflamed fibrous tissue, scattered within which are myriad granulomas, and its surface facing the implant displays a synovial-like aspect. The mono- and polykaryonic macrophages, constituting the granulomatous response, ingest and abut on the wear particles. Amongst the intermediary substances of inflammation elaborated by the lymphocytes and macrophages of the LIM, factors which stimulate the osteoclasts play the pivotal role in as much as progressive bone resorption is associated with progressive growth of the IM and, hence, with incremental interfacial motion, interfacial deposition of wear particles and inflammatory-granulomatous response. The ensuing vicious circle culminates in aseptic loosening of the arthroplasty. The morphological features of the LIM, though characterized by a stereotypical reaction pattern, are, in their details, closely linked with the nature of the diverse components of the composite joint replacement. The histological appearances of the bone-implant interface of stable and loose arthroplasties, the tissular reactions to polymethylmethacrylate, polyethylene, polyacetal, metals and hydroxyapatite as well as the characteristics of cemented and cementless porous-coated, press-fit and hydroxyapatite-coated prostheses are described. PMID- 7877559 TI - Retrieval studies on calcium phosphate-coated implants. AB - The search for the improvement of implant fixation in bone resulted several years ago in the introduction of calcium phosphate coatings on orthopaedic (and dental) implants. Since then many animal experiments, especially on hydroxylapatite coatings, have been performed. By now the first promising results from clinical studies are also available. In this review, the plasma-spray process is described and some of the current techniques for the analysis of retrieved implants are discussed. It is now widely understood that the calcium phosphate hydroxylapatite is osteoconductive. Various experimental animal studies revealed the capability of calcium phosphate coatings to enhance implant fixation, especially under specific or less optimal conditions such as a with a porous implant, loose fit, micromotion or experimental arthritis. Clinical studies, including the analysis of retrieved hydroxylapatite coated hip implants, confirmed these promising results and as a consequence, hydroxylapatite coated total joint prostheses are now used on a large scale. Two questions that are closely related with each other are very actual, e.g. the strength of the coating-substrate interface and how stable or crystalline should hydroxylapatite coatings be for a proper clinical function? There does not yet seem to be a consistent answer to these questions. PMID- 7877560 TI - Use of osteoinductive implants in the treatment of bone defects. AB - Osteogenic proteins (OPs) are a family of bone matrix polypeptides isolated from a variety of mammalian species, including mouse, rat, bovine, monkey, and man. OPs initiate chondroblastic differentiation in pluripotent mesenchymal progenitor cells, followed by the synthesis of new bone by endochondral ossification. OPs have the ability to induce healing of osteoperiosteal defects in several animal models, supporting a possible therapeutic role in the reconstruction of bone defects. OPs are responsible for the osteoinductive capacity of demineralized bone matrix (DBM) implants, which may also prove to be clinically useful. Preliminary studies using purified, naturally occurring human osteogenic proteins in the clinical management of non-unions have reported promising results. A prospective, randomized clinical trial is currently underway, comparing recombinant human osteogenic protein-1 (rhOP-1) to autograft in the treatment of tibial non-unions. The use of osteogenic protein implants to augment or replace autogenous and allogenous bone grafts will reduce morbidity, and circumvent the risk of disease transmission associated with transplantation. PMID- 7877561 TI - Fractographic analysis of failed porous and surface-coated cobalt-chromium alloy total joint replacements. AB - Fractographic analyses were performed on retrieved porous and surface-coated cobalt-chromium alloy prostheses which were revised because of metallurgical fracture. Two femoral neck fractures and one fractured post of a femoral component of a total knee replacements were retrieved and analyzed via light, stereo and scanning electron microscopy (SEM). In all cases, fatigue was the mechanism of failure. The life time of these prostheses was 3-5 years. The porous coating; microstructural features, including large grains, carbides, porosity, inclusions and defects; design and manufacturing defects were all likely causative factors in these fatigue failures. In light of these and other reported fractures, further study of fatigue mechanisms and improvement of design and manufacturing processes are warranted. PMID- 7877562 TI - Systemic and local silver accumulation after total hip replacement using silver impregnated bone cement. AB - In a patient, at revisional Christiansen total hip arthroplasty, silver impregnated bone cement was used as prophylaxis against deep infection. Five years later the patient developed serious neurological deficits, and the prosthesis was loose. The loose Christiansen prosthesis and the silver impregnated bone cement were removed and a Charnley prosthesis inserted. Intra operatively the concentration of silver in fluid drawn from the hip joint was assessed to be about 1000 times the normal serum reference value, and tissue samples from the acetabulum were densely impregnated with silver. During the following 2 years the serum concentration of silver decreased from more than 60 times to 20 times the normal; simultaneously the patient partially recovered from her grave muscle paralysis. PMID- 7877563 TI - Metallosis due to abnormal abrasion of the femoral head in bipolar hip prosthesis. Implant retrieval and analysis in six cases. AB - We report on six cases of metallosis which developed in bipolar hip prosthesis due to ceramic screws used for fixation of bone grafts. Two patients experienced severe metallosis due to abnormal abrasion of the femoral head. At the revision surgery, proliferated black synovia was found. Analyses of the retrieved prostheses revealed numerous small particles of alumina ceramic on the inner surface of the bearing insert of UHMWPE. These particles came from the broken ceramic screws, and scraped away the metallic femoral head resulting in severe metallosis. In four patients, the outer head came into direct contact with ceramic screws and mild metallosis was observed at revision surgery. PMID- 7877564 TI - Clinical hemolysis with the St. Jude heart valve without paravalvular leak. AB - In 1990 and 1991 we operated on 2 patients with persistent clinical hemolysis, in the absence of perivalvular leaks, who had had their mitral valves replaced with St. Jude Medical valve (SJMV) prostheses. The valves had been implanted 14 months and 3 months before, respectively. There were no other discernible causes for the hemolysis and when each SJMV was replaced the hemolysis disappeared in that patient. The first valve was not tested in the laboratory owing to its loss, but it looked normal. The second valve was tested and found to have regurgitation well within the usual limits for this valve. Fringe pattern interferometry indicated that the leading edge of each leaflet was flatter and less smooth than that of another SJMV. Reviewing the literature we find that idiopathic, persistent clinical hemolysis in recipients of St. Jude mechanical heart valves is a rare phenomenon, which has appeared in 4 reports totaling 9 cases. We discuss the suggested mechanisms involved, and add the possibility of leading leaflet edge characteristics. PMID- 7877565 TI - An examination of two retrieved long-term human implant Bjork-Shiley valves. AB - Two retrieved long-term human implant Bjork-Shiley valve prostheses were examined for wear. The prostheses were retrieved at necropsy from a double implant patient that had died from causes unrelated to the valves twelve years post implantation. Both prostheses were the Bjork-Shiley conical tilting disc type heart valves with Haynes 25 alloy orifice and a Pyrolite Carbon disc. A size 21 mm valve had been implanted in the aortic position and a size 27 mm valve had been implanted in the mitral position. Wear had occurred on the valves in regions of mutual contact between the disc and orifice struts during valve opening and closing. Wear mark depths and types were consistent with previous observations on Pyrolite Carbon Bjork-Shiley and Lillehi-Kaster prostheses. No evidence of cavitation nor strut fatigue damage was observed on either valve prosthesis. Wear that occurred on the valves was insignificant and of no consequence to valve function. PMID- 7877566 TI - On the durability of pyrolytic carbon in vivo. AB - The durability of pyrolytic carbon heart valve components was examined from the point of view of number implanted, documentation of wear on explanted components, and from the aspect of fatigue. Failures of pyrolytic carbon components were found to be few in number. A model describing the time course of events and successful usage of pyrolytic carbon components in heart valves was developed. The model is based on the yearly shipments of pyrolytic carbon components or valves, starting with 1969. The model indicates that about 2 million components have been successfully implanted, resulting in accumulative experience of over 10 million patient years. The wear of pyrolytic carbon, based on analysis of explanted heart valves, was found to be minimal. Additional wear data obtained on explanted components confirms the earlier observation that wear in vivo in less than that observed in vitro. The recently discovered fatigue behavior of pyrolytic carbon was found to have no demonstrated practical impact on the durability of pyrolytic carbon components used in existing mechanical heart valves. PMID- 7877567 TI - Biomaterial-host interactions: consequences, determined by implant retrieval analysis. AB - Prosthetic biomaterials have had a profound impact on reconstructive surgery but complete biocompatability remains illusive. This review considers the retrieval analysis of four common prosthetic structures: the hip, the knee, heart valves, and blood vessels. We show that despite a fine record of early success, deterioration due to mechanical failure or deleterious host responses to the implant may compromise long term function. The eventual retrieval and detailed analysis of implanted structures provides an invaluable opportunity to determine the characteristics of implant success or failure and to provoke the development of still better materials. PMID- 7877568 TI - Evaluation of the Omniflow collagen-polymer vascular prosthesis. AB - The Omniflow Vascular Prosthesis (OVP) is a truly integrated bio-synthetic composite of polyester mesh and ovine connective tissue components. In animal and human studies, the prosthesis has demonstrated long-term patency rates comparable and often better than alternate surgical replacements, with minimal aneurysmal or thrombotic problems. Immunohistological and TEM analysis of explants of OVP I provide good evidence for the excellent in vivo performance and are reviewed below. In addition, new data from explants of the OVP II, a later version of the Omniflow, are also described. These explant analyses have been enhanced by use of a library of highly specific monoclonal antibodies which can discriminate between collagens from different species. PMID- 7877569 TI - Effectiveness of injectable filler materials for smoothing wrinkle lines and depressed scars. AB - Both synthetic and biological materials have been used for smoothing wrinkle lines and depressed scars. Injectable fillers provide a convenient and easy alternative to surgical methods to treat dermal defects. Optimally, injectable fillers augmenting dermal tissue should exhibit properties similar to the dermal collagen network, providing a stable matrix for long-term correction but also being subject to the dynamic changes that occur to dermal tissue during the aging processes. At present, only biological materials are available on a commercial basis, although a number of synthetic injectables are being evaluated in clinical trials. The long-term effectiveness of most commercial materials has been limited prompting questions about the cost-benefits of such treatment. In this regard, the effectiveness of the injectable fillers, particularly of biological materials, will be discussed as will the difficulties involved in determining the expected result (effectiveness) for specific materials and in providing methods of measuring effectiveness. PMID- 7877570 TI - Silicone breast implant rupture: common/serious complication? AB - Of the potential health risks of silicone breast implants it is the concern about implant durability, life span and the possible association with connective tissue disease which has attracted most attention. A prospective study addressing these factors was therefore undertaken over an 11 month period. 51 patients presenting with significant capsular contracture, suspected prosthesis rupture or unrelieved implant-induced anxiety underwent revisional breast surgery after biochemical, haematological and immunological screening. Of these 51 patients (83 breasts), 14 (19 breasts) had ruptured implants (23% incidence). These were all smooth prostheses belonging to a cohort manufactured more than 10 years ago; their mean in situ duration being 12 years vs. 5.5 years for the intact group (p = 0.0024; Kruskal-Wallis one-way ANOVA). There were no systemic complications from implant rupture and the mean blood silicon level was normal. One patient with pre existing pernicious anaemia had elevated autoantibodies. The mean ESR in the ruptured implant group was 6 mm/hour. It is concluded that rupture of breast implants is not as uncommon as hitherto thought and is strongly correlated with their in situ duration. In this study implant gel leakage was not associated with serious systemic effects. PMID- 7877571 TI - Interactions of enzymes and fungi with crosslinked polyurethanes prepared for biomedical applications. AB - Shelf life and long-term environmental stability of polyurethanes intended for percutaneous applications and various biomedical applications are largely depend on their resistance to fungal attack and growth. Two classes of aliphatic crosslinked polyurethanes based on hexamethylene diisocyanate (HDI) and bicyclo hexyl-methane diisocyanate (SM DI) were subjected to cell-free enzymatic degradation using hydrolytic and oxidative enzymes and to fungal attack and fungal growth using Aspergillus niger and Penicillium Sp. The present crosslinked polyurethanes are not susceptible to degradation by hydrolytic enzymes. The marginal loss of tensile strength in buffered solution of papain is attributed to plasticization by the absorbed components of the enzyme solution. The PEG based crosslinked polyurethanes are marginally susceptible to degradation by lactic dehydrogenase solution. The present polyurethanes are resistant to fungal attack. The fungal growth was not observed with PTMG and PPG based Polyurethanes, however, a marginal growth was observed with PEG based polyurethanes. PMID- 7877572 TI - Modern concepts of packaging surgical needles and suture. AB - A new, innovative packaging system for surgical needles and sutures has been developed that meets the special needs of surgical technologists. This packaging system consists of an overwrap, or breather pouch, as well as an innerwrap containing the suture swaged to a surgical needle. The flaps of the overwrap are offset and serrated to facilitate the opening and sterile transfer of the inner packet to the sterile field. The inner packet contains either a plastic labyrinth, or craft board that maintains the suture as straight as possible until knot construction. The needle swaged to a suture is 'parked' in foam to protect its sharp cutting edges and point. PMID- 7877573 TI - The Minnesota Health Care Quality and Coverage Act. PMID- 7877574 TI - Minnesota care: round 4. PMID- 7877575 TI - Child abuse article missed important resource. PMID- 7877576 TI - Dementia and Alzheimer's disease. Indications, diagnosis, and treatment. AB - At least 6 million Americans suffer from some form of dementia. More than half of those patients are afflicted with Alzheimer's disease, a progressive, degenerative neurological disorder. Reaching the diagnosis of Alzheimer's, however, is often difficult since Alzheimer's can be accurately diagnosed only after all other options are ruled out. The process is painstaking, but it's also the crucial link in ensuring proper diagnosis and treatment. There's no cure yet for Alzheimer's, but researchers are narrowing in on possible causes of the disease and identifying patients who may be predisposed to developing it. Some of the most compelling research focuses on the presence of one or more of the apolipoprotein E4 genes. Researchers also continue to develop new drugs and physical therapies. In the Twin Cities, several drug studies are underway, and community resources are available to provide Alzheimer's patients and their families with information on everything from support groups to assisted-living arrangements. PMID- 7877577 TI - Hospitals can take steps to ease end-of-life decision making. PMID- 7877578 TI - Will Minnesota keep its edge in health care quality? PMID- 7877579 TI - The board of medical practice improves its complaint handling system. PMID- 7877580 TI - Applying the healing arts to health system reform. PMID- 7877581 TI - Critical care for the health system. PMID- 7877582 TI - Recollection. PMID- 7877583 TI - [Clinical and experimental studies of septic DIC in surgical patients, in terms of its characteristic features and pathogenesis]. AB - I have experienced 35 cases of DIC in my department during last 8 years. These cases were divided into a septic and non-septic groups based on their back ground, and compared their clinical symptoms and various laboratory findings. The results showed the septic DIC group could be characterized as follows: (1) impairment of the vital organs was more clearly manifested, while hemorrhagic symptoms were mild, (2) the laboratory tests showed almost no tendency for fibrinogen or alpha 2-PI to be decreased or PIC to be increased, (3) the blood PAF (Platelet Activating Factor) level was clearly higher and showed an inverse relationship with the platelet count. On the basis of these clinical findings, I speculated septic DIC involves suppression of secondary fibrinolysis and participation of PAF. In experiment A, I investigated the effects of endotoxin (Et) on the activity of plasminogen activator (PA) in the rabbit renal cortex. In both in vitro and in vivo systems, I could demonstrate the renal cortex PA activity was significantly suppressed by Et. Then, in experiment B, I could confirm, (1) PAF caused a drop in the blood pressure and a decrease in the platelet count that were similar to those induced by Et, and that Et caused a decrease in the platelet count that was inversely accompanied by an increase in PAF, (2) PAF antagonist showed greater efficacy than a protease inhibitor in suppressing the decrease in the blood platelet count. PMID- 7877585 TI - [Experimental studies on the morphological changes in the endocrine pancreas after gastrectomy]. AB - I report the detailed morphological changes of the endocrine pancreas after gastrectomy, by PAP stain method, using gastrectomized rats. Regarding the number ratio and the occupied area-ratio of the B and A cells in each Langerhans islet, there was no difference in each group. But regarding the D cell in totally gastrectomized rats, especially in EJ group (total gastrectomy, esophagojejunostomy with Braun anastomosis), the most notable morphological changes were recognized, namely the occupied area-ratio and the number-ratio of the D cell in each Langerhans islet increased to 3.57 +/- 1.64% and 11.73 +/- 3.89%. In gastrectomized rats, the structure of the B and A cells in each Langerhans islet was comparatively well-preserved. In totally gastrectomized rats, especially in EJ group, the more remarkable increase of the D cell in each Langerhans islet was recognized. It is though that because of the loss of the stomach, the secretory changes of the gut hormones and the accelerated intestinal transit and etc., the D cell increased compensatorily. PMID- 7877584 TI - [Evaluation of medicinal lymph node dissection in advanced gastric cancer]. AB - In order to improve the results of surgical treatment in advanced gastric cancer, we performed preoperative targeted chemotherapy for metastatic lymph nodes. The solution which contained aclarubicin adsorbed on activated carbon was submucously injected around gastric tumor under endoscopic observation 2-7 days prior to the operation. We termed this method medicinal lymph node dissection (MLD). Our standard surgical treatment (SST) for gastric cancer consists of gastrectomy and extended lymph node dissection (N1 and N2 lymph nodes). Patients of curative resection with histologically positive lymph node metastasis were enrolled, as the subjects. We compared the cumulative survival rate in 47 patients treated with SST+MLD (MLD group) with that in 125 patients treated with SST only (control group). Five year survival rates in the MLD and control groups were 60% and 48%, respectively. The MLD group showed significantly higher survival rate in patients with N3, N4 and infrapyloric lymph node metastasis. A significant difference of the survival rate suggests the efficacy of SST+MLD against micrometastasis in N3 and para-aortic lymph nodes. The SST+MLD therapy is recommended to the advanced gastric cancer, especially in the lower third of the stomach. PMID- 7877586 TI - [Disturbance of sexual function after an operation for rectal cancer and a fundamental study of the relationship between autonomic nerves and arteries in the pelvis of dogs]. AB - Clinical studies of 15 male patients with resected rectal cancer and 30 canine experiments revealed a close relationship between autonomic nerves and arterial flow in the pelvis. In clinical cases transection of the hypogastric nerve (HGN) and the sympathetic trunk did not affect the erectile function in the postoperative course. In animal experiments transection of these nerves did not affect the increase in inner pressure of the penis cavernosum. Internal pudendal arterial (IPA) flow affecting the erectile function was decreased by transection of the bilateral pelvic splanchnic nerve (PSN). Transection of the PSN on one side did not affect the erectile function. In postoperative cases in which only one side of the lower grade branches of the PSN were preserved, the erectile function was preserved. In animal experiments in which the PSN of one side was disturbed, the IPA flow of the same side decreased, while the flow of the other side increased. The effect of norepinephrine hydrochloride on canine vascular smooth muscle was examined in vitro. Vascular smooth muscle strips from the IPA, relaxed longitudinally. This relaxation was suppressed by phentolamine methylate (alpha-blocker). It is also conceivable that the erectile function through the PSN is controlled by the sympathetic nerve, not by the parasympathetic nerve. PMID- 7877587 TI - [Nipple-preserved mastectomy (Glt+Ax) as a standard operation for p-stage I, II breast cancer]. AB - In this paper, surgical results of nipple-preserved mastectomy (Glt+Ax) for breast cancer were compared with those of radical mastectomy. In p-stage I breast cancer cases, survival and loco-regional disease-free rate of the nipple preserved cases were equivalent to those of radical mastectomy group. Although nipple-preserved cases had inferiority to the radical mastectomy cases in the survival rate in p-stage II cases, loco-regional disease-free rate of nipple preserved cases was equal to that of radical mastectomy cases. On the basis of these results, nipple-preserved mastectomy can be a standard operation of p-stage I, II breast cancer in point of the local control at least. PMID- 7877588 TI - [Limulus test (factor G pathway) positive substance during cardiopulmonary bypass]. AB - Limulus cascade reaction is found to be frequently activated by the plasma in the patients undergoing cardiopulmonary bypass (CPB). Recently, it is considered that this phenomenon occurs by factor G pathway reactive activity (GPRA) rather than endotoxin that activates factor C pathway. In the present report, we investigated circulating endotoxin and GPRA in 32 patients undergoing CPB. Plasma was pretreated by the New PCA method, and assay was performed by two limulus tests; Toxicolor (reactive with endotoxin and GPRA) and Endospecy (endotoxin-specific). Thirty-two patients were classified into four groups by clinical diagnosis, Group A; dissecting aneurysm of the aorta (6 patients), Group B; ischemic heart disease (9 patients), Group C; heart valve disease (8 patients), Group D; congenital heart disease and myxoma in left atrium (9 patients). GPRA in Ringer's lactate hardly increased during previous circulation before operation. The highest plasma GPRA concentration in all patients was observed at the end of CPB, 415 +/- 342pg/ml, but plasma endotoxin concentration was within normal range. At the end of CPB, plasma GPRA concentrations were 761 +/- 180pg/ml in Group A, 646 +/- 341pg/ml in Group B, 230 +/- 86pg/ml in Group C, and 113 +/- 65pg/ml in Group D. GPRA increase ratio (GPRA increase value/CPB time) of Groups A and B was significantly higher (p < 0.05) than that of Groups C and D. It was suggested that the origin of plasma GPRA during CPB was not the CPB circuit but the tissue of the patients. PMID- 7877589 TI - [Development of novel elastomeric surgical adhesive: biomechanical and pathohistological heeling process]. AB - A newly developed novel elastometric surgical elastoma based on reactive hydrophylic urethane was tested in vivo experiment of dog models for its anastomotic performances and functions at various periods. The carotid artery as well as the abdominal aorta were completely transected and reanastomosed by applying the adhesive materials. The serial studies on patency rate, tensile strength, elasticity as well as histopathological examinations were undertaken up to the longest period of 180 days after the implantation. The overall patency rate in carotid anastomosis was 93.9%, where in the abdominal aorta, 100% of patency rate was obtained. The tensile strength at the anastomosis surpassed the stress derived from pulsation and internal tension within 7 days of implantation. No significant change in stiffness parameter beta was observed in 180 days of implantation. Histopathological studies at the site of anasotmosis revealed the presence of mild inflammatory reaction in earlier phase and well healing of tissue without foreign body reaction in later period. This material proved to be an effective surgical adhesive in reference to the compliance mateching so as to facilitate to expect for the clinical application in cardiovascular surgical practice. PMID- 7877590 TI - [Penetrating atherosclerotic ulcer of the iliac artery combined with abdominal aortic aneurysm--a case report]. AB - A 76-year-old woman with abdominal aortic aneurysm was referred to our hospital with a complaint of abdominal pulsatile mass. CT and angiogram revealed infrarenal abdominal aortic aneurysm (AAA) with right common iliac aneurysm. AAA was replaced with the bifurcated Dacron graft and iliac aneurysm was resected concomitantly. A focal perforation of intima and medial wall hematoma were found in the iliac aneurysm. These findings corresponded with penetrating atherosclerotic ulcer (PAU). PAU in the abdominal aorta may form the abdominal aortic false aneurysm, and may cause the rupture of aneurysm. It is an critical sign of "aortic catastrophe". PMID- 7877591 TI - [Anti-proteolytic effect of insulin-like growth factor-1 (IGF-1) in C2C12 myotubes and its mechanism: preliminary report]. PMID- 7877592 TI - [Alterations of peripheral insulin sensitivity, energy expenditure, and substrate oxidation in patients with cancer: preliminary report]. PMID- 7877594 TI - Effects of ischaemia, reperfusion and alpha 1-adrenergic receptor stimulation on the inositoltrisphosphate receptor population in rat heart atria and ventricles. AB - Binding sites specific for inositol 1,4,5-trisphosphate (InsP3) have been demonstrated in sarcoplasmic reticulum vesicles isolated from heart muscle. Scatchard analysis of a binding isotherm indicated a high as well as a low affinity binding site [1]. In this study a comparison was made between InsP3, binding to crude microsomal membranes prepared from rat heart atria and ventricles respectively. Results obtained showed a four-fold higher incidence of binding to atrial membranes. Furthermore, the receptor populations of the atria and ventricles behaved differently during conditions causing fluctuations in tissue InsP3, levels, viz. ischaemia, reperfusion and alpha 1-adrenergic stimulation. Reperfusion, as well as phenylephrine stimulation, caused an increase in InsP3 levels associated with down-regulation of the ventricular InsP3 receptor population while binding to atrial binding sites was elevated. In the ventricular population this down-regulation was the result of a reduction in Bmax alone with no changes in the Kd values of the high- or the low-affinity binding sites. The reason(s) for the differential response of the atrial and ventricular InsP3 receptor populations to changes in InsP3 levels, remains to be established. PMID- 7877595 TI - Platelet-derived growth factor B-chain gene expression in mesangial cells: effect of phorbol ester on gene transcription and mRNA stability. AB - We have investigated the effect of phorbol 12-myristate 13-acetate (PMA) on platelet-derived growth factor (PDGF) B-chain gene transcription as well as on mRNA stability in cultured human mesangial cells. Addition of actinomycin to cells stimulated with PMA decreases steady state levels of PDGF-B chain mRNA analysed by solution hybridization assay. PDGF-B chain gene transcription was also assayed directly by measuring elongation of transcripts in isolated nuclei followed by hybridization of labeled RNA transcripts to a cDNA encoding for PDGF B chain. Our data show that PMA induces PDGF-B chain gene transcription by approximately 2-fold. alpha-Amanitin, an RNA polymerase II inhibitor, blocked transcription by more than 70%. In addition, we determined the effect of PMA on the halflife of PDGF-B chain mRNA directly by pulse chase method. In human mesangial cells, the PDGF-B chain mRNA exhibited halflife of approximately 105 min. In the presence of PMA, the halflife of PDGF-B chain mRNA was reduced to approximately 72 min. These studies indicate that regulation of PDGF-B chain gene by PMA in human mesangial cells involves a coordinate effort at the level of transcription and mRNA stability. PMID- 7877593 TI - Physiological concentrations of purines and pyrimidines. AB - The concentrations of bases, nucleosides, and nucleosides mono-, di- and tri phosphate are compared for about 600 published values. The data are predominantly from mammalian cells and fluids. For the most important ribonucleotides, average concentrations +/- SD (microM) are: ATP, 3,152 +/- 1,698; GTP, 468 +/- 224; UTP, 567 +/- 460 and CTP, 278 +/- 242. For deoxynucleosides-triphosphate (dNTP), the concentrations in dividing cells are: dATP, 24 +/- 22; dGTP, 5.2 +/- 4.5; dCTP, 29 +/- 19 and dTTP 37 +/- 30. By comparison, dUTP is usually about 0.2 microM. For the 4 dNTPs, tumor cells have concentrations of 6-11 fold over normal cells, and for the 4 NTPs, tumor cells also have concentrations 1.2-5 fold over the normal cells. By comparison, the concentrations of NTPs are significantly lower in various types of blood cells. The average concentration of bases and nucleosides in plasma and other extracellular fluids is generally in the range of 0.4-6 microM; these values are usually lower than corresponding intracellular concentrations. For phosphate compounds, average cellular concentrations are: Pi, 4400; ribose-1-P, 55; ribose-5-P, 70 and P-ribose-PP, 9.0. The metal ion magnesium, important for coordinating phosphates in nucleotides, has values (mM) of: free Mg2+, 1.1; complexed-Mg, 8.0. Consideration of experiments on the intracellular compartmentation of nucleotides shows support for this process between the cytoplasm and mitochondria, but not between the cytoplasm and the nucleus. PMID- 7877597 TI - Beta-adrenoreceptors of multiple affinities in a clonal capillary endothelial cell line and its functional implication. AB - beta-Adrenoreceptor has been studied in a clonal capillary endothelial cell line established from the vascular bed of the bovine adrenal medulla. [3H]Dihydroalprenolol ([3H]DHA) binding to the isolated plasma membranes from these cells has demonstrated the presence of beta-adrenoreceptors with two different affinities. The dissociation constants (Kd) have been found to be 0.27 +/- 0.09 x 10(-9) M and 2.96 +/- 0.31 x 10(-9) M, respectively with the corresponding Bmax of 5.1 +/- 0.05 and 70.0 +/- 0.2 pmol/mg protein, respectively. Inhibition of [3H]DHA binding to the beta-receptor by atenolol (a beta 1-antagonist) and ICI 118,551 (a beta 2-antagonist) has suggested that the IC50cor (= Ki) for atenolol and ICI 118,551 for high affinity site are 0.08 +/- 0.03 x 10(-12) M and 0.25 +/- 0.08 x 10(-12) M, respectively. This, therefore, indicates that both atenolol and ICI 118,551 are able to displace the bound ligand effectively but the beta 1-selective antagonist atenolol is 3 times more potent than its beta 2 counterpart, ICI 118,551. Displacement of [3H]DHA binding to the endothelial cell plasma membrane by the agonists isoproterenol, epinephrine and norepinephrine has established a relative order of Ki for these agents as isoproterenol (0.56 +/- 0.19 x 10(-9) M) < epinephrine (0.77 +/- 0.26( 9) M) > or = norepinephrine (0.71 +/- 0.24 x 10(-9) M) for the high affinity site. The corresponding values for the low affinity site, however, are 4.62 +/- 0.64 x 10(-9) M, 6.21 +/- 0.86 x 10(-9) M and 5.90 +/- 0.82 x 10(-9) M, respectively for the same agonists. Increased intracellular cAMP accompanied with cellular proliferation in the presence of isoproterenol has suggested not only the coupling of beta-adrenoreceptors to the adenylate cyclase system but also its involvement in endothelial cell proliferation. PMID- 7877596 TI - Membrane associated proteoglycans in rat testicular peritubular cells. AB - Confluent testicular peritubular cells derived from immature rats were used to study membrane associated proteoglycans (PG). Peripheral material (heparin releasable), membrane and intracellular material (Triton X-100 releasable) were collected, purified by anion exchange chromatography then characterized by gel filtration and by hydrophobic interaction chromatography, followed by enzymatic digestion and chemical treatment. The peripheral material was constituted of two populations of PG (Kav = 0 and 0.10 on Superose 6 column), each containing both heparan sulfate proteoglycans (HSPG) and chondroitin proteoglycans (CSPG) and perhaps a hybrid PG (HSCSPG). These PG being not retained on an octyl Sepharose column, they were devoided of hydrophobic properties. The integral membrane proteoglycans isolated on the basis of their hydrophobic properties represented 20% of the Triton X-100 releasable material, and were exclusively constituted of proteoheparan sulfate. There were no relationships between this membrane HSPG and the peripheral HSPG as evidenced by pulse chase experiments. The mode of intercalation of the hydrophobic HSPG in the cell membrane was studied. The majority of these macromolecules (80%) were sensitive to trypsin and only a minor proportion (20%) were sensitive to phosphatidylinositol specific phospholipase C. Thus, about 80% of the hydrophobic HSPG were intercalated in the cell membrane by a hydrophobic segment of the core protein whereas about 20% were associated with the cell membrane via a phosphatidylinositol residue covalently bound to the core protein of the PG. PMID- 7877598 TI - Expression of human aspartyl-tRNA synthetase in COS cells. AB - Mammalian aspartyl-tRNA synthetase (DRS) occurs in a multi-enzyme complex of aminoacyl-tRNA synthetases, while DRS exists as free soluble enzymes in bacteria and yeast. The properties of human DRS transient expressed in COS cells were examined. After transfection of COS cells with the recombinant plasmids pSVL-63 that contained hDRS cDNA coding and non-coding sequences, and pSV-hDRS where the non-coding sequences were deleted, DRS in the transfected COS cells significantly increased compared to mock transfected cells. COS cells transfected with pSV-hDRS delta 32 that contained N-terminal 32 residue-coding sequence deleted hDRS cDNA showed no increase in DRS activity. Northern blot analysis showed that concentrations of corresponding mRNAs of hDRS and hDRS delta 32 were greatly enhanced in transfected cells. The increases in the level of the transcripts were much higher than those of the corresponding proteins. Gel filtration analysis showed that hDRS in pSV-hDRS transfected cells expressed as a low molecular weight form of hDRS and pSV-hDRS delta 32 transfected cells did not. Epitope tagging and indirect immunofluorescence microscopy was used to localize hDRS. Both hDRSmyc and hDRS delta 32myc were localized in the cytoplasm and showed diffused patterns. These results showed that hDRS has little tendency to aggregate in vivo and suggested that the N-terminal extension in hDRS was not involved in the expression and sub-cellular localization of hDRS, but may play a role in the maintenance of enzymatic activity of hDRS in COS cells. PMID- 7877600 TI - Antioxidant properties of dehydrozingerone and curcumin in rat brain homogenates. AB - The present study investigates the inhibition of lipid peroxidation by dehydrozingerone and curcumin in rat brain homogenates. Both the test compounds inhibited the formation of conjugated dienes and spontaneous lipid peroxidation. These compounds also inhibited lipid peroxidation induced by ferrous ions, ferric ascorbate and ferric-ADP-ascorbate. In all these cases, curcumin was more active than dehydrozingerone and dl-alpha-tocopherol. PMID- 7877601 TI - Importance of various types of metabolic inhibition for cell damage caused by direct membrane damage. AB - Cell damage is caused by energy depletion or by direct membrane damage, or a combination when a direct membrane damage affects energy depleted cells. In this report it was investigated whether the extent of direct membrane damage induced by lysophosphatidyl choline (LPC) or phospholipase C (PhC) on quiescent fibroblasts depended on the metabolic state of the cells. When glycolysis was inhibited cell damage was always extensively increased, whereas cell damage was also increased to a minor degree when exposed to PhC during sole inhibition of oxidative phosphorylation. Acceleration of glycolysis in cells with a low rate of glycolysis resulted in a dramatic improvement of the membrane susceptibility within a few minutes. Thus, susceptibility of the cell membrane to direct membrane damage depends on the metabolic state. The results also emphasize previous findings that glycolysis has a special role in maintaining membrane function and integrity. PMID- 7877599 TI - Signal transduction pathways of muscarinic receptors in circular smooth muscle from the rabbit caecum. AB - The effects of muscarinic acetylcholine receptor stimulation on phosphoinositides breakdown and adenylate cyclase activity were examined in the circular smooth muscle of the rabbit caecum. In Myo-[3H]inositol-labeled circular smooth muscle cells, carbachol caused a concentration-dependent increase in [3H]inositol phosphates ([3H]IPs) accumulation (EC50 of 3 +/- 1 microM). The M1-selective antagonist pirenzepine (PRZ), the M2-selective AF-DX 116 (11-2[[2-[(diethyl amino)methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6Hypyrido[2,3 b][1,4]benzodiazepin-6-one) and the M3-selective para-fluoro hexahydrosiladifenidol (p-F-HHSiD) inhibited the carbachol-induced [3H]inositol phosphates accumulation with the following order of potency; p-F-HHSiD > PRZ > AF DX 116. In saponin-permeabilized circular smooth muscle cells, carbachol and GTP gamma [S] elicited a concentration-dependent increase in [3H]inositol phosphates accumulation. The concentration-response curve for GTP gamma [S] was shifted to the left when cells were incubated with 1 microM carbachol. The [3H]inositol phosphates accumulation elicited by simultaneous addition of 0.1 microM GTP gamma [S] and 1 microM carbachol to permeabilized cells was significantly decreased (78.28 +/- 18.23% inhibition) when cells were preincubated for 5 min with 0.1 mM GDP beta [S]. In nonpermeabilized cells, pertussis toxin did not alter the carbachol-induced increase in [3H]inositol phosphates accumulation. On the other hand, the 0.1 mM carbachol-induced inhibition of forskolin-stimulated adenylate cyclase activity in circular smooth muscle homogenates was significantly reversed by atropine and AF-DX 116, whereas PRZ and p-F-HHSiD were ineffective (muscarinic antagonists were used at 1 microM final concentration).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877602 TI - Eicosanoid production in experimental alcoholic liver disease is related to vitamin E levels and lipid peroxidation. AB - We investigated the association between vitamin E, lipid peroxidation and eicosanoid production in experimental alcoholic liver injury. We used the intragastric feeding rat model in which animals were fed corn oil and ethanol (CO+E) and corn oil and dextrose (CO+D) for 2 and 4 week periods. At sacrifice, we measured plasma levels of alpha-tocopherol, 8-isoprostane, thromboxane B2 (TXB2) and 6-ketoprostaglandin F1 alpha (6-KetoPGF1 alpha). Animals fed CO+E had significantly lower concentrations of alpha-tocopherol and higher concentrations of 8 isoprostane at both 2 and 4 weeks. a significant inverse correlation was seen between alpha-tocopherol concentrations and the TXB2: PGF1 alpha ratio (r = 0.72, p < 0.01). A positive correlation was seen between the TXB2: PGF1 alpha ratio and 8 isoprostane levels (r = 0.84, p < 0.001). These results suggest that vitamin E depletion and enhanced lipid peroxidation may affect eicosanoid metabolism in experimental alcoholic liver disease in such a way so as to increase the thromboxane to prostacyclin ration. PMID- 7877604 TI - Expression of hepatic calcium-binding protein regucalcin mRNA is decreased by phenobarbital administration in rats. AB - The effect of phenobarbital on the expression of calcium-binding protein regucalcin mRNA in rat liver was investigated. The change of regucalcin mRNA levels was analyzed by Northern blotting using liver regucalcin cDNA (0.9 kb of open reading frame). Phenobarbital (4, 8 and 12 mg/ 100 g body weight) was intraperitoneally administered to rats 3 times with 24 h intervals, and the animals were sacrificed by bleeding at 24 h after the last administration. The hepatic regucalcin mRNA levels were markedly reduced by phenobarbital administration. This decrease was about 50% of control level with the 12 mg/100 g dose. Moreover, the hepatic regucalcin concentration was significantly decreased by the administration of phenobarbital (12 mg/100 g), although the serum regucalcin concentration was not altered appreciably. Meanwhile, serum transaminases (GOT and GPT) activities were not increased by the administration of phenobarbital (4 and 12 mg/100 g). The present study demonstrates that the expression of hepatic regucalcin mRNA is decreased by phenobarbital administration in rats, suggesting that regucalcin does not have a role in drug metabolism related to phenobarbital. PMID- 7877603 TI - Heterogeneity in rabbit liver cytochrome P-450 LM2 observed by cation exchange HPLC: partial biochemical characterization of the two major LM2 subfractions. AB - Cytochrome P450 LM2 (CYPIIB4) from phenobarbital-induced rabbit liver microsomes, purified to only one band in SDS-PAGE, was further resolved in five peaks by cation exchange HPLC. The two major peaks were partially characterized. Both of them have the amino terminal sequence Met-Glu and the same Cys content. They exhibited the same spectral absorption maximum and similar binding constants for 1-benzylimidazole and imidazole. However, binding of benzphetamine was different. One subfraction presented a Michaelis-Menten type binding curve, but the other presents a non-typical one with an additional high affinity binding site. These subfractions of cytochrome P450 LM2 slightly differed in their catalytic activities with benzyloxy- and pentoxyresorufin substrates. On the contrary, no heterogeneity was observed for P450 LM4. PMID- 7877605 TI - Alterations of mitochondrial oxidative metabolism in rabbit urinary bladder after partial outlet obstruction. AB - Previous studies demonstrated that one of the most significant cellular responses of the rabbit urinary bladder to partial outlet obstruction is a 50% decrease in the activities of the mitochondrial enzymes citrate synthase and malate dehydrogenase, when calculated as either activity per unit mass or activity per mg protein. A major question arose from these studies: Are the mitochondrial enzyme activities per mitochondrion reduced, or is the number of mitochondria per unit tissue mass reduced? The current experiments were designed to study the sequential changes in the activities of mitochondrial oxidative enzymes following partial outlet obstruction. The activities of NADH-cytochrome c reductase (NCCR), cytochrome oxidase (CO), citrate synthase (CS) and malate dehydrogenase (MDH) were measured in whole tissue homogenates and in mitochondrial preparations of separated bladder mucosa and muscle, from normal bladders, and, from hypertrophied bladders at 1, 3, and 7 days following partial outlet obstruction. The results can be summarized as follows: 1) Whole tissue homogenates: Activities of all enzymes were reduced to approximately 50% of control at 1 day following partial outlet obstruction. NCCR and CO activities returned to 75 and 85% of control respectively by 7 days post-obstruction; CS activity did not show any significant recovery over the 7 day period. 2) Mucosal and smooth muscle mitochondrial preparations: Activities of all enzymes were decreased significantly by 50% or greater at 1 day following partial outlet obstruction. The cytochrome (NCCR and CO) enzyme activities returned to control levels by 7 days post-obstruction; CS activity showed only a minor recovery over this time period. These results show that mitochondrial enzyme activity is significantly impaired immediately following partial outlet outlet obstruction, and whereas the activity of the cytochrome enzymes NCCR and CO recover to control levels (in the mitochondrial preparations) within 7 days post obstruction, the Krebs cycle enzymes (CS and MD) show no significant recovery. Thus, the regulatory mechanisms for the cytochromes is significantly different from that for the enzymes of the krebs cycle. PMID- 7877606 TI - Isoproterenol inhibits cyclic AMP-mediated but not insulin-mediated translocation of the GLUT4 glucose transporter isoform. AB - Isoproterenol is a beta adrenergic agonist whose effects have been attributed to the generation of cAMP. Previous studies have shown that it inhibits glucose transport in adipocytes without changing the number of insulin-responsive glucose transporters (GLUT4) on the cell surface. However, we have shown previously that cAMP stimulates translocation of GLUT4 to the cell surface in adipocytes (Kelada et al. J Biol Chem 267, 7021-7025, 1992). We therefore further investigated the mechanisms involved in isoproterenol regulation of glucose transport. Consistent with the effects of dibutyryl cAMP, we found that a low concentration of isoproterenol (10 nM) stimulated glucose transport and the translocation of GLUT4 from the low density microsomal fraction to the plasma membrane. By contrast, a higher concentration of isoproterenol (1 microM) did not stimulate transport or GLUT4 translocation and furthermore inhibited dibutyryl cAMP-stimulated GLUT4 translocation. This inhibitory effect was specific for cAMP since isoproterenol had no effect on insulin-stimulated GLUT4 translocation. We conclude that isoproterenol has a biphasic effect on glucose transport, mediated by acute translocation of GLUT4 at low concentrations and by inhibition of intrinsic activity at high concentration, both of which may be explained by effects of cAMP. It has a further cAMP-independent effect at high concentration to inhibit cAMP-mediated translocation of GLUT4. PMID- 7877607 TI - The salivary gland 42-kDa phosphoprotein is a single-stranded DNA-binding protein with characteristics of the epithelial casein kinase N42 in Chironomus tentans. AB - The DNA-binding and phosphorylation properties of a rapidly phosphorylated nuclear 42-kDa phosphoprotein and of its two structurally related proteins, pp43 and pp44 in Chironomus tentans salivary glands were investigated. pp42, pp43 and pp44 bind promoter probes of the ecdysterone controlled I-18C gene and of the joint histone H2A/H2B genes in a sequence-selective and single-stranded DNA (ssDNA) specific manner. Rapid phosphorylation appears to give pp42 and pp43 uniquely hydrophilic characters making them soluble in the aqueous phase during phenol treatment. Dephosphorylation of the nuclear proteins markedly stimulates the ssDNA-binding activity of pp42 but not of pp43 and pp44. All three phosphoproteins are sensitive to heparin and the transcription inhibitor 5,6 dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) in vitro, but their sensitivity to heparin is more than one order of magnitude lower than that of casein kinase II. The heparin sensitivity of pp42 and pp43 is, however, similar to that described for a previously identified nuclear 42-kDa phosphoprotein in a Chironomus tentans epithelial cell line, casein kinase N42 (CKN42). pp42 and pp43 bind with high affinity to a Phosvitin-Sepharose matrix, like casein kinase I, II and N42, and can be eluted with high salt buffers from the affinity column. In intact salivary gland cells, microinjected (gamma-32P)GTP labels pp42 in a heparin sensitive manner, and this GTP-phosphorylation of pp42 could be competed out by a large excess of phosvitin. (gamma-32P)ATP-based phosphorylation of pp42 was uninfluenced by phosvitin in intact cells. The experimental data suggest that the salivary gland 42-kDa phosphoprotein, pp42, is a ssDNA-binding protein with characteristics of the epithelial CKN42. PMID- 7877608 TI - Partial outlet obstruction of the rabbit bladder results in changes in the mitochondrial genetic system. AB - In the rabbit, partial outlet obstruction of the urinary bladder results in significant changes in the physiology, cellular structure, and cellular metabolism of that organ. One of the most striking changes observed is a 50% decrease in oxidative metabolism. Here we investigate whether the function of the mitochondrial (mt) genetic system is altered in rabbit bladder tissue following partial outlet obstruction. Southern analyses of total DNA prepared from bladder tissue excised as a function of time after initiation of partial outlet obstruction showed that the relative number of copies of the mt genome decreases as much as 10-fold during the first 7 d after obstruction, and that this attenuated mt genome copy number is maintained until at least 14 d post obstruction. Northern analyses, in contrast, showed that mt COII and cytochrome b transcript levels initially decrease but recover to control levels by about 5 d after obstruction; that level is maintained through 14 d post-obstruction. Enzymatic analysis of cytochrome oxidase and NADH cytochrome c reductase activities in obstructed bladder tissue gave results which paralleled the pattern in the mt RNA analyses. Surprisingly, transcript levels for the mt-related nuclear COIV gene rapidly decreased to about 50% of control levels following obstruction and remained there until 14 d post-obstruction. These results indicate that partial outlet obstruction of the rabbit bladder leads to significant changes in the status and expression of the mt genetic system in bladder tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877609 TI - The relationship of hydrophobic tubulin with membranes in neural tissue. AB - Brain membrane preparations contain tubulin that can be extracted with Triton X 114. After the extract is allowed to partition, 8% of the total brain tubulin is isolated as a hydrophobic compound in the detergent-rich phase. Cytosolic tubulin does not show this hydrophobic behaviour since it is recovered in the aqueous phase. Membrane tubulin can be released by 0.1 M Na2 CO3 treatment at pH > or = 11.5 in such a way that the hydrophobic tubulin is converted into the hydrophilic form. These results suggest that tubulin exists associated with some membrane component that confers the hydrophobic behaviour to tubulin. If the tissue is homogenized in microtubule-stabilizing buffer containing Triton X-100, the hydrophobic tubulin is isolated from the microtubule fraction. This result indicates that the hydrophobic tubulin isolated from membrane preparations belongs to microtubules that in vivo are associated to membranes. Therefore, hydrophobic tubulin (tubulin-membrane component complex) can be obtained from membranes or from microtubules depending on the conditions of brain homogenization. PMID- 7877610 TI - Prooxidant and antioxidant effects of Trolox on ferric ion-induced oxidation of erythrocyte membrane lipids. AB - The prooxidant and antioxidant actions of Trolox were examined in an in vitro system measuring ferric ion-induced oxidation of erythrocyte membrane lipids. Trolox was found to produce a concentration-dependent biphasic effect on the ferric ion-stimulated lipid peroxidation, with the mode of action being similar to those produced by reducing-agent antioxidants, such as ascorbic acid and reduced glutathione, and iron chelator, such as desferrioxamine. Phytic acid, a potent iron chelator, could suppress the prooxidant actions of Trolox and desferrioxamine, but not those of ascorbic acid and reduced glutathione. The ability of Trolox to stimulate ferric ion-catalyzed ascorbate oxidation, as similar to the action produced by ethylenediaminetetraacetic acid, indicates the presence of iron-chelating activity. The ensemble of results suggests the possible involvement of iron chelation in the prooxidant action of Trolox in ferric ion-stimulated lipid peroxidation reactions. PMID- 7877611 TI - Changes in UsnRNA biosynthesis during rat liver regeneration. AB - Partial hepatectomy (P.H.) induces a partially synchronized growth response of liver under normal regulation of growth. In this phase changes in cellular morphology, radial distribution pattern of cells and other biological as well as major biochemical changes are well documented. Here, we have shown that the cellular content of UsnRNAs altered during this proliferative phase as well. The level of spliceosomal UsnRNAs (U1, U2, U4-U6) gradually decreased by 30-50% upto 48 hrs of P.H. followed by gradual increase to reach the normal level within one month of P.H. The U3 snRNA level on the other hand, was nearly equal to that in normal liver at 48 hrs of P.H. but in 24 and 72 hrs of P.H. its level was high (4 fold) in contrast to that in other UsnRNAs. Thus, it is clear from our data that the level of all the six UsnRNAs decreased during 48 hrs of P.H. compared to that after first 24 hrs. This has been correlated in the kinetics of UsnRNAs' synthesis (in terms of labelling) in isolated hepatocytes, where the rate of labelling of all the six UsnRNAs increased 20-30% in 24 hrs regenerating hepatocytes (R.H.) followed by sharp decrease by 30-50% within next 24 hrs, compared to that in the normal hepatocytes. But from 72 hrs onwards in R.H. the rate of labelling of all the six UsnRNAs again increased by 30-50% (compared to that in normal hepatocytes) followed by decrease of their labelling-rate to reach the normal level in R.H. within one month of P.H.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877613 TI - INSIGHT: Pit-1/GHF-1: a pituitary-specific transcription factor linking general signaling pathways to cell-specific gene expression. PMID- 7877612 TI - Age-related changes in linoleic acid bioconversion by isolated hepatocytes from spontaneously hypertensive and normotensive rats. AB - This study points out the hepatocyte interconversion of the linoleic acid family during hypertension. Hepatocyte delta 6 desaturase activity was higher in 1 month old spontaneously hypertensive rats than in normotensive controls. A similar tendency was observed in 6 month-old SHR. delta 5 desaturase activity was higher only in 1 month-old spontaneously hypertensive rats as compared to controls. Desaturase activities were particularly high at the age of 6 months. The hepatocyte fatty acid composition showed an impairment of n-6 polyunsaturated fatty acid metabolism in spontaneously hypertensive animals. Changes were greater in the young prehypertensive rats than in adults. A storage of n-3 long chain fatty acids is remarkable in adult hypertensive rats, suggesting an alteration in peroxisomal oxidation. Such modifications may be related to the prostaglandin precursors availability to peripheral tissues such as kidney. PMID- 7877614 TI - Molecular mechanisms of dominant negative activity by nuclear hormone receptors. PMID- 7877615 TI - Reconstitution of thyroid hormone receptor and retinoic acid receptor function in the fission yeast Schizosaccharomyces pombe. AB - We report here a characterization of the thyroid hormone receptors (T3Rs), retinoic acid receptors (RARs), and retinoid X receptors (RXRs) by reconstituting their actions in the fission yeast Schizosaccharomyces pombe. S. pombe provide a well defined and readily manipulated genetic background devoid of known endogenous nuclear hormone receptors. All the receptors tested, when introduced exogenously into S. pombe, induced high levels of reporter gene activation in response to physiological concentrations of hormone ligand. In these properties, the S. pombe system exhibits significant advantages over the previously employed Saccharomyces cerevisiae system. Use of the S. pombe system permitted the elucidation of previously undescribed differences in the DNA sequence recognition properties of different isoforms of the RXR and RARs, and the identification of apparently novel forms of response element for RXRs and RARs. Intriguingly, the v erb A allele of T3R, a transcriptional repressor in vertebrate cells, acts as a transcriptional activator both in S. cerevisiae and in the evolutionarily highly divergent S. pombe, underscoring the importance of cellular factors in the regulation of receptor transcriptional activity. PMID- 7877616 TI - Phosphorylation of Ser530 facilitates hormone-dependent transcriptional activation of the chicken progesterone receptor. AB - Phosphorylation regulates the activities of many proteins, including transcription factors. However, the evidence for the significance of phosphorylation in steroid hormone receptor action is mainly indirect. In this study, one of the hormone-induced phosphorylation sites of chicken progesterone receptor, Ser530, was mutated to alanine, a nonphosphorylatable amino acid, and the transcriptional activity of the mutant receptor was compared with that of wild type in a transient cotransfection assay. The results showed that this mutation resulted in reduced transcriptional activity of chicken progesterone receptor at low hormone concentrations but did not affect the maximal activity of the receptor at saturating levels of hormone, suggesting that the phosphorylation at Ser530 influences the response of the receptor to its ligand. The decreased sensitivity of the mutant receptor is not due to a decrease in hormone-binding affinity, leading to our hypothesis that Ser530 phosphorylation stabilizes the receptor in its active state, perhaps by preventing its reassociation with heat shock proteins or by maintaining a conformation suitable for interaction with other transcription factors. PMID- 7877617 TI - Msx-2/Hox 8.1: a transcriptional regulator of the rat osteocalcin promoter. AB - We recently defined an element (ACTAATTGG) within the rat osteocalcin (OC) promoter at -84 to -92 which provides approximately 70% of basal promoter activity in osteoblastic cell lines and binds a specific nuclear factor found in OC-producing ROS 17/2.8 osteosarcoma cells. Since this element closely resembles the recently described Msx-1 (Hox 7.1) homeodomain DNA binding cognate, we examined rodent osteoblastic cells lines for expression of Msx homeodomain encoding messages. We have found and cloned a cDNA for rat Msx-2 (Hox 8.1) from a ROS 17/2.8 library and detect high levels of expression in various osteoblastic cell lines (ROS 17/2.8, RCT3, RCT1) as well as in culture passage 3 neonatal rat calvarial osteoblastic cells. Little to no expression was detected in phenotypically immature MC3T3E1 osteoblastic cells or in a variety of nonosteoblastic (ROS 25/1, C2C12, TRAB 11) mesenchymal cell lines. Dexamethasone (DEX) down-regulates Msx-2 message levels in both RCT3 and ROS 17/2.8 cells. Recombinant rat Msx-2 homeodomain expressed in Escherichia coli as a glutathione S-transferase fusion protein binds to the rat OC promoter region -74 to -100 as determined by gel shift analysis. Recognition is dependent upon the intact ACTAATTGG motif at -84 to -92. In transient cotransfection assays using MC3T3E1 cells (which expresses very little or no endogenous Msx-2), Msx-2 suppresses the rat OC promoter 2- to 3-fold via the Msx-2 binding motif at -84 to -92. However, in ROS 17/2.8 cells, where a high level of endogenous Msx-2 mRNA is present, expression of exogenous Msx-2 does not suppress the rat OC promoter; surprisingly, Msx-2 further augments basal promoter activity by approximately 50 70%, again dependent upon the ACTAATTGG motif at -84 to -92. These data directly demonstrate that the Msx-2 homeodomain binds the rat OC promoter and that Msx-2 can act as a sequence-specific transcriptional regulator of the rat OC promoter in cultured osteoblastic cell lines. This activity is dependent upon the specific osteoblastic cellular context, similar to previous observations in nonosseous systems with other homeodomain transcription factors. These data suggest that Msx 2 may play a role in the transcriptional regulation of the osteoblast phenotype during development in the morphogenetic fields where it is expressed. PMID- 7877618 TI - Heterodimeric interaction of the retinoic acid and thyroid hormone receptors in transcriptional regulation on the gamma F-crystallin everted retinoic acid response element. AB - Previously, we have identified a hormone response element (gamma F-HRE) composed of an everted repeat of the half-site (A/G)GGTCA motif separated by 8 base pairs that mediates retinoic acid (RA) activation of the gamma F-crystallin promoter. Here, we report that this element is bound by the thyroid hormone (T3) receptor in the form of heterodimers with either the retinoid X receptor (RXR) or the retinoic acid receptor (RAR). The T3R/RXR heterodimer binds to this element with high affinity but the transcriptional activity of the T3 receptor on this element is effectively antagonized by RAR alpha. Thus, RAR alpha exerts a dominant effect on the gamma F-HRE-everted repeat by mediating both RA activation and preventing T3 response. Although RAR/T3R heterodimers bind to the gamma F-HRE, they do not appear to be involved in transcriptional regulation since they bind with low affinity, and their ability to bind DNA is dramatically decreased by T3. Repression requires the DNA- and ligand-binding domains of RAR alpha and is consistent with a competitive DNA binding model of repression. However, in vitro binding studies indicate that RAR/RXR heterodimers form less stable interactions with the gamma F-HRE compared with T3R/RXR heterodimers; this suggests that in vivo the binding affinity of RAR/RXR heterodimers may be enhanced by accessory factors. PMID- 7877619 TI - Characterization of retinoic acid- and cell-dependent sequences which regulate zif268 gene expression in osteoblastic cells. AB - We have previously shown that retinoic acid (RA) induces differentiation in an osteoblastic cell line derived from embryonic rat calvaria and that RA has selective effects on zif268 gene expression in these preosteoblastic cells,distinct from those in more mature osteoblasts. In this study we demonstrate that the RA-dependent transcriptional increase in zif268 gene expression is mediated by the interaction of RA receptors (RARs) with a 17 base pair sequence in the zif268 promoter containing a single half-site motif (GTTCA), identical to each of the direct repeats seen in the RAR beta 2 gene. The sequence appears relatively RA-specific, since the zif268 RA-responsive element is not activated by 1,25-dihydroxyvitamin D3 or thyroid hormone (T3). However, cotransfection of RAR expression vectors and an SV-40 promoter chloramphenicol acetyltransferase (CAT) construct containing the single zif268 RA-responsive motif into CV-1 cells demonstrates that the alpha-, beta-, and gamma-RARs transactivate through this element. Extensive mutagenesis of the zif268 promoter region containing the RA response element (RARE) motif confirms that the transactivation and nuclear protein binding activity of this region requires only the half-site motif. The direct involvement of RAR in this DNA-protein interaction has been demonstrated by competitive gel retardation analysis using consensus RAREs and super-shifting of the DNA-protein complex with mouse alpha- or gamma-RAR monoclonal antibodies. In addition, we found that cell-specific suppression of RA-stimulated zif268 gene expression can be attributed to a 29 base pair nucleotide sequence, located downstream of the RA-responsive region in the zif268 gene. This sequence appears to be bound specifically by nuclear protein(s) from several cell types, including osteoblasts. The presence of this sequence in cis to the zif268 RARE or the consensus beta RARE completely blocks the RA-responsiveness of the zif268 gene in differentiated osteoblasts. These data extend the broad spectrum of RA-responsive sequences necessary for DNA binding and transactivation to include regulation via single RARE half-site motifs and suggest that the lack of RA responsiveness in differentiated osteoblasts may be mediated by cell-specific suppression of gene expression. PMID- 7877620 TI - Transmembrane domain interactions are necessary for negative cooperativity of the insulin receptor. AB - Insulin binding to the human insulin receptor (HIR) is characterized by negatively cooperative site-site interactions that give rise to a curvilinear Scatchard plot. Insulin binding to recombinant secreted HIRs is linear, suggesting that interactions between the transmembrane or cytoplasmic domains of the receptor heterodimers may be responsible for the generation of negative cooperativity. To determine the domains responsible, a series of HIR cDNAs encoding C-terminal deletion mutations was constructed; HIR.delta CT, HIR.delta TK, HIR.delta TMCP-encoded deletions of the tyrosine kinase regulatory, the tyrosine kinase regulatory and catalytic, the cytoplasmic and the transmembrane and cytoplasmic domains, respectively. When expressed in COS cells, all cDNAs were processed to mature alpha- and beta- subunits. The affinity of HIR.delta CT, HIR.delta TK, and HIR.delta CP for insulin were 2- to 3-fold greater than that of wild type HIR (HIR.WT) which was 4- to 5-fold greater than that of HIR.delta TMCP. Scatchard plots of HIR.delta CT, HIR.delta TK, and HIR.delta CP, like that of HIR.WT, were curvilinear. In contrast, that of HIR.delta TMCP was linear. We conclude that constraints imposed on HIR structure by membrane insertion and/or interactions between receptor transmembrane domains are essential for the generation of negative cooperativity. Further, interactions between the C terminal regions of the cytoplasmic domains appear to modulate affinity for insulin. PMID- 7877621 TI - Regulation of the sheep beta-lactoglobulin gene by lactogenic hormones is mediated by a transcription factor that binds an interferon-gamma activation site related element. AB - Polypeptide and steroid hormones regulate the transcription of milk protein genes in the mammary gland. The promoter sequence motifs and factors through which these hormones mediate their effects in vivo are not clearly defined. Milk protein binding factor (MPBF) is a factor that has recognition sites in the promoters of many milk protein genes including three sites in the promoter of the sheep beta-lactoglobulin (BLG) gene. Mutagenesis of these sites reduced expression of the BLG gene in lactating mammary glands of transgenic mice but did not affect the tissue specificity of the transgene. Furthermore, mutation of all three sites abolished the response of the BLG gene to lactogenic hormones in HC11 mammary cells. Together these results indicate that MPBF mediates the effects of lactogenic hormones in the mammary gland but does not play a role in determining mammary specificity. The similarity between the MPBF binding site and the gamma interferon activating site suggests that MPBF is related to the STAT family of cytokine-induced transcription factors. PMID- 7877622 TI - Phosphorylation-independent desensitization of the luteinizing hormone/chorionic gonadotropin receptor in porcine follicular membranes. AB - Phosphorylation of several G protein-coupled receptors mediates desensitization. This study determined whether LH/CG receptor was phosphorylated under conditions that promoted human CG (hCG)-induced desensitization. Cell-free desensitization of LH/CG receptor-mediated adenylylcyclase activity in porcine follicular membranes occurred in the presence of GTP and was time- and hCG dose-dependent, reaching 36-52% upon preincubation at 30 C for 40 min with 1.0 micrograms/ml hCG. However, under conditions that promoted GTP-dependent desensitization, there was no apparent phosphorylation of LH/CG receptor (obtained via immunoprecipitation) by endogenous membrane-associated protein kinases using [gamma-32P]GTP or [gamma 32P]ATP as phosphate donor. On the other hand, LH/CG receptor (88-90 kilodaltons) from both control and hCG-incubated membranes was phosphorylated in vitro by the catalytic subunit of cAMP-dependent protein kinase (protein kinase A). However, protein kinase A (in the absence of exogenous GTP) did not promote LH/CG receptor desensitization. These data demonstrate that, unlike with other G protein-linked receptors, LH/CG receptor phosphorylation by endogenous follicular membrane associated protein kinase(s) does not mediate desensitization. PMID- 7877623 TI - Holoprotein formation of human chorionic gonadotropin: differential trace labeling with acetic anhydride. AB - The effects of holoprotein formation in human CG (hCG) on the reactivities of several of the individual amino groups of each subunit were investigated by differential trace labeling with [3H]acetic anhydride. The alpha- and beta subunits were labeled separately, as was hCG, under conditions chosen to ensure that an average of less than one amino group was modified per molecule. Although the beta-subunit contains fewer amino groups than the alpha-subunit, most of the 3H incorporation occurred in beta at the N-terminal region. Chemical and enzymatic cleavage of the subunits enabled us to identify several individual amino groups and, from measurements of the incorporated radioactivity of the free subunits and intact hormone, determine their protection factor, which is a measure of the reactivity and thus of the local environment and changes thereof upon holoprotein formation. Lys51 and Lys91 of alpha were approximately 2-fold more reactive and less reactive, respectively, in the alpha beta complex than in the free subunit. The alpha-amino group of alpha was characterized by comparable reactivities in the heterodimer and free subunit, as was Lys44/Lys45 when analyzed as a pair; the reactivity of alpha-Lys44 was slightly less in the holoprotein than in the free subunit. The alpha-amino group and Lys2 of beta could not be resolved by available cleavage procedures; consequently they were analyzed as a pair and found to be some 2-fold less reactive in the heterodimer than in the free subunit, as was Lys104 of beta. From these results, we can conclude that subunit assembly produces changes in the microenvironments of several amino groups, attributable to steric effects, specific intermolecular interactions, and localized conformational changes. Analysis of these data with reference to the recently determined crystal structure of hydrogen fluoride treated hCG enabled a distinction to be made of these possibilities for several of the amino groups. PMID- 7877624 TI - Pit-1 binding sites mediate transcriptional responses to cyclic adenosine 3',5' monophosphate through a mechanism that does not require inducible phosphorylation of Pit-1. AB - The ability of Pit-1 to mediate transcriptional responses to cAMP has been explored. To test the ability of Pit-1 to mediate transcriptional responses to cAMP, an expression vector was prepared for a mutant Pit-1 in which the major sites of phosphorylation by the cAMP-dependent protein kinase were eliminated. Before using the mutant Pit-1 to study transcriptional regulation, we first examined the ability of the protein to be phosphorylated in vivo in response to cAMP. Transfection and in vivo labeling experiments confirmed that the mutant Pit 1 did not support cAMP-inducible phosphorylation. The ability of the wild type or mutant Pit-1 to mediate transcriptional responses to cAMP was assessed in cotransfection experiments using reporter genes containing either the proximal region of the rat PRL gene or seven copies of a Pit-1 binding site placed upstream of a minimal promoter. Surprisingly, the wild type and mutant Pit-1 expression vectors supported similar responses to cAMP. To further assess the ability of Pit-1 to mediate responses to cAMP, a GAL4-Pit-1 fusion gene was prepared. Although a GAL4-cAMP response element binding protein fusion gene was found to permit transcriptional responses to cAMP, the GAL4-Pit-1 gene was unresponsive. These findings demonstrate that although Pit-1 can facilitate the ability of the PRL promoter to respond to cAMP, phosphorylation of Pit-1 is not required for this response. It seems likely that additional factors that interact with Pit-1 binding sites are important for mediating transcriptional responses to cAMP. PMID- 7877625 TI - A Pit-1 phosphorylation mutant can mediate both basal and induced prolactin and growth hormone promoter activity. AB - The transcription factor Pit-1 has been shown to be important for both the developmental and homeostatic regulation of expression of the PRL and GH genes in pituitary cells. However, little is known about possible covalent modifications in Pit-1 that might mediate its transactivational properties. Previous studies showing that Pit-1 is a phosphorylation substrate for either protein kinase A or C, or their cellular inducers, led us to investigate whether phosphorylation of Pit-1 is required for its function in either basal or induced cellular activity of either the PRL or GH promoters. The transactivational properties of wild type Pit-1 were compared with those of Pit-1(A3), mutated in the three known phosphorylation sites. At saturating levels of Pit-1 expression vectors, activation of transient basal expression in HeLa cells of constructs (-1957)PRL CAT or (-244)GH-CAT by RSV-Pit-1(A3) was, respectively, about 50% and 65% as strong as by RSV-Pit-1. Hence, phosphorylation at the sites mutated in Pit-1(A3) is not critically required for basal transactivation of either promoter but may modulate this activity. RSV-Pit-1 and RSV-Pit-1(A3) were equally effective in mediating estrogen receptor stimulation of (-1957)PRL-CAT expression in HeLa cells, thus revealing no phosphorylation requirement for the prerequisite for Pit 1 in estrogen receptor action on the PRL estrogen response element.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877626 TI - The combination of Pit-1 and Pit-1T have a synergistic stimulatory effect on the thyrotropin beta-subunit promoter but not the growth hormone or prolactin promoters. AB - Pit-1 is a pituitary-specific transcription factor with protein expression limited to thyrotrope, somatotrope, and lactotrope cells of the anterior pituitary gland. We have recently described a thyrotrope-specific variant isoform of Pit-1, called Pit-1T, which contains an additional 14 amino acids in the activation domain generated by an alternate 3'-splicing choice. Pit-1T, in the presence of Pit-1, stimulates the thyrotropin beta-subunit (TSH beta) promoter in a thyrotrope-derived cell that lacks all Pit-1 isoform proteins. Three laboratories have identified another Pit-1 splice variant, called Pit-1 beta, which contains an additional 26 amino acids in the activation domain that is generated by a similar 3'-alternate splice choice. Pit-1 beta has been shown to stimulate the GH promoter, but not the PRL or TSH beta promoters. In this report, we evaluate the effect of the three Pit-1 isoforms (Pit-1, Pit-1T, and Pit-1 beta) on the GH, PRL, and TSH beta promoters when introduced into different cell types. The combination of Pit-1 and Pit-1T had a synergistic stimulatory effect on the TSH beta promoter, but not on the PRL or GH promoters in a thyrotrope derived cell line that lacks all Pit-1 protein isoforms (alpha TSH cells). When added to GH3 cells, which lack only the Pit-1T isoform, Pit-1T selectively stimulated the TSH beta promoter and not the GH or PRL promoters, suggesting that the thyrotrope-specific Pit-1T exhibits a promoter-specific effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877627 TI - NOT, a human immediate-early response gene closely related to the steroid/thyroid hormone receptor NAK1/TR3. AB - By analyzing the early genetic response of human T cells following mitogenic activation we have identified NOT, a member of the steroid/thyroid hormone family of receptors. NOT has all structural features of steroid/thyroid hormone receptors (C2C2 zinc-finger domain, ligand binding domain), but is rapidly and only very transiently expressed after cell activation, which is clearly at variance with classical steroid receptors such as glucocorticoid or estrogen receptors. NOT gene induction is independent of de novo protein synthesis, defining NOT as an immediate-early response gene. Short-lived NOT mRNA (4.2 kilobases) expression could be observed in vitro in a greater number of tissue types following activation by a variety of distinct stimuli. In vivo, NOT mRNA expression was detected exclusively in the brain, where a very strong signal was observed. By immunoblot analysis of human T cell lysates with NOT specific antisera two activation-dependent protein bands (66 and 59 kilodaltons) could be detected. NOT gene was localized to human chromosome 2q22-q23. Sequence comparison revealed that NOT is the human homolog of the murine NURR1 and rat RNR 1. Moreover NOT is closely related to NAK1/TR3, a previously identified human orphan steroid receptor. Several lines of evidence indicate that NOT and NAK1/TR3 form a distinct and exclusive subgroup of orphan steroid receptors, whose expression characteristics in vitro and in vivo resemble the expression of nonsteroid immediate-early transcription factors such as jun and fos. NOT and NAK1/TR3 thus may function as general coactivators of gene transcription rather than participate in the induction of specific target genes, as is the case with classical steroid receptors. PMID- 7877628 TI - Detection of human papillomavirus by in situ polymerase chain reaction in paraffin-embedded cervical biopsies. AB - The efficiency of the in situ polymerase chain reaction (PCR) for the detection of human papillomavirus (HPV) DNA sequences in 20 cervical biopsies fixed with buffered formalin, paraffin-embedded and revealed negatively by conventional in situ hybridization (ISH) has been investigated. The biopsies were classified histologically into condylomata acuminata without dysplasia, cervical intraepithelial neoplasia and carcinoma in situ. Amplified HPV DNA was performed after an optimal proteolytic digestion using one pair of consensus oligonucleotide primers located in the L1 ORF of HPV 6 and ISH was carried out after the PCR assay with a cocktail of biotinylated HPV probes. Viral DNA was detected in 100% of high grade squamous intraepithelial lesions (SIL) and in 50 to 60% of low grade SIL. The high sensitivity of the in situ PCR applicable to paraffin-embedded archival biopsies facilitated the detection of cells poorly reactive by conventional ISH. In situ PCR appeared clearly an efficient tool to investigate HPV infection in tissue sections. PMID- 7877629 TI - Activated THP-1 cells depress mitochondrial respiration in Hep G2 cells infected with influenza B virus. AB - Influenza B virus has been aetiologically linked to Reye Syndrome (RS), but the mechanism(s) by which this pathogen could disrupt liver metabolism and produce the hepatic mitochondrial injury characteristic of the syndrome are unknown. In this study, two mechanisms by which infection of hepatocytes with influenza B virus could disrupt cellular metabolism were investigated. (1) virus-induced increase in pro-oxidant iron with subsequent iron-induced lipid peroxidation (LP) and (2) increased membrane permeability. Hep G2 cells, a well-differentiated continuous human liver cell line derived from a hepatoblastoma, were infected with allantoic-fluid derived influenza B Lee/40 virus (AFDV) at a multiplicity of infection of 10 for 24 h; productive infection was confirmed by both haemagglutination of chick erythrocytes and by plaque assay. Infection of Hep G2 cells preloaded with 59Fe-transferrin resulted in increased release of 59Fe (153 +/- 17% of controls, P < 0.03). However, the iron released did not result in increased LP (assessed by thiobarituric acid reactive substances; TBARS). To confirm that this lack of of increase in TBARS was not due to insensitivity of the cell line to pro-oxidant iron, cells were exposed to 15 microM iron ascorbate for 60 min. Production of TBARS was increased (122 +/- 4% of controls, P < 0.0003). Release of 51Cr from infected cells was also increased (128 +/- 12% of controls, P < 0.05); thus the infected cells exhibited a generalized increase in membrane permeability. However, infection did not depress mitochondrial respiration (as assessed by the formation of MTT-f3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl-tetrazolium bromide-formazan. To determine if the combination of viral infection and soluble products of activated macrophages would affect mitochondrial respiration, infected hepatocytes were exposed to the supernatant fluid from THP-1 cells which had previously been incubated with lipopolysaccharide at 100 ng ml-1 for 18 h. This supernate did depress the formation of MTT-f (81 +/- 5% of controls, P < 0.03). We conclude that influenza B virus does productively infect Hep G2 cells, and does increase hepatocyte membrane permeability. This effect does not impair mitochondrial respiration directly. However, infection does act in concert with soluble products of activated macrophages to depress hepatic mitochondrial respiration. Whether this interaction can be explained by virus-induced permeability changes and/or other effects of infection deserves further investigation. PMID- 7877630 TI - Differentiation of Sarcocystis neurona from eight related coccidia by random amplified polymorphic DNA assay. AB - Four isolates of Sarcocystis neurona from horses with equine protozoal myeloencephalitis and eight species of coccidia from the genera Sarcocystis, Toxoplasma or Eimeria were differentiated using the random amplified polymorphic DNA assay. A single, common, 550-bp DNA fragment was amplified from the DNA of each S. neurona isolate using a 16-nucleotide primer. Crosshybridization analyses among S. neurona isolates showed that DNA fragments had at least partial sequence homology. The primer generated several DNA fragments, including a 550-bp DNA fragment, from S. cruzi, Eimeria falciformis, E. neischulzi, E. ahsata and E. bovis. DNA hybridization analyses indicated no sequence homology between these fragments and the 550-bp DNA fragment generated from S. neurona. The S. neurona 550-bp DNA fragment also did not hybridize with genomic blots of various other coccidia. These results suggest that the S. neurona DNA fragment may be exploited as a species-specific probe for this parasite. PMID- 7877631 TI - Evaluation of nested polymerase chain methods for the detection of human coronaviruses 229E and OC43. AB - Currently, the diagnosis of human respiratory coronavirus infection is either slow or insensitive. This paper describes nested polymerase chain reaction assays for the detection of human coronaviruses OC43 and 229E. The specificity and sensitivity of the assays have been determined and they have been applied to the detection of the viruses in nasal aspirates. These assays are more rapid and sensitive than cell culture and may replace the latter as the diagnostic method of choice. PMID- 7877632 TI - Detection of Clostridium botulinum type F using the polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used to amplify a portion of the Clostridium botulinum type F toxin gene. An 1137-bp fragment was amplified from 11 different strains of type F C. botulinum with primers derived from the published sequence of type F strain no. 202. This fragment was not amplified from the DNA of C. botulinum types A, B and E, or from other clostridial organisms examined. When used as a hybridization probe, the 1137-bp PCR-generated fragment generated from one of the type F strains (the proteolytic strain type F Langeland) hybridized to the PCR products from all other type F toxin-producing strains tested. Portions of fragments amplified from the type F Langeland strain were sequenced. The sequence of this strain was found to exhibit approximately 3% variation from the published sequence of the non-proteolytic type F strain no. 202. Primers designed to pair with the regions of maximum sequence variation between strain 202 and the Langeland strain gave amplification products only with DNA from type F strains that exhibited the same proteolytic properties as the strain from which the primer sequences were derived. These findings underscore the need to consider variations in sequence when designing oligonucleotide probes and PCR primers in order to avoid false negative results. PMID- 7877633 TI - Nucleotide sequence and strand displacement amplification of the 70K protein gene from mycobacteria. AB - We isolated and determined the nucleotide sequence of the 70K gene from nine mycobacteria and from two related non-mycobacteria with the goal of obtaining a region of requisite specificity to serve as a mycobacterial genus-specific probe. Two different primer sets were then designed to amplify the 70K gene using strand displacement amplification. Using one of the primer sets, 10 different mycobacteria were readily detected with sensitivities of 100 molecules DNA, and with only cross-reactivity to two non-mycobacteria. The other set of primers that were tested amplified the same set of mycobacteria, but exhibited no crossreactivity with non-mycobacterial DNAs. By employing one of the primer sets, we were able to successfully amplify with high sensitivity three different target DNA sequences comprised of the 70K mycobacterial genus target, an IS 6110 (M. tuberculosis complex) target, and an internal amplification control using SDA. These results demonstrate the potential of the 70K gene to serve as a mycobacterial genus-specific probe, and demonstrate the first multiplex amplification by SDA of three DNA targets. PMID- 7877634 TI - Rapid and practical detection of beta-globin mutations causing beta-thalassemia by fluorescence-based PCR-single-stranded conformation polymorphism analysis. AB - We report a useful method for daily clinical examination for the diagnosis of thalassemia. We applied a fluorescence-based image analyser to a non radioisotopic PCR-single-stranded conformation polymorphism (SSCP) analysis to detect mutations in the beta-globin gene. PCR primers were labelled with rhodamine X and the amplified fragments from the beta-globin gene were resolved by non-denaturing polyacrylamide gel electrophoresis. After loading, the glass plate was set in the image analyser and scanned with a green laser. We detected four common mutations in exon I and two major mutations in intron 1 of the beta globin gene isolated from patients with beta-thalassemia. Moreover, to discriminate mutations and natural polymorphisms, we used primers including one base mismatch at the polymorphic site, which can substitute the polymorphic site by a constant base in the PCR amplified fragment. This fluorescence-based system was simple to operate and results were obtained rapidly as clear image data. Therefore, once the optimal conditions of the electrophoresis are determined, this system will be suitable for daily clinical use, especially for screening of molecular defects and for the prenatal diagnosis of genetic disorders. PMID- 7877635 TI - Use of oligonucleotide probes to analyse the homology of the oprF gene among clinical and heterologous immunotype strains of Pseudomonas aeruginosa. AB - The conservation of oprF gene among 25 clinical Pseudomonas aeruginosa strains and a set of 17 serotype-specific representative strains of the international antigen typing scheme (IATS) was analysed by dot-blotting using five specific oligonucleotide probes. The oligo 1, 2, 3, 4, 5 correspond to five different regions of the oprF gene and hybridized strongly with respectively 88%, 88%, 76%, 94% and 71% of the IATS strains and 88%, 96%, 92%, 88% and 92% of the clinical strains. A parallel study performed with the whole oprF gene showed a lack of specificity of this probe: indeed, the probe hybridized not only with the 42 Pseudomonas aeruginosa strains but also with Escherichia coli and Salmonella minnesota. This study suggests that the gene sequence encoding the protein F is not totally conserved among Pseudomonas aeruginosa strains. PMID- 7877636 TI - Chemiluminescent and colorimetric detection of a fluorescein-labelled probe and a digoxigenin-labelled probe after a single hybridization step. AB - The objective of the simple and fast method we describe is the simultaneous hybridization of two non-radioactive probes and their detection from the same blot, using two different systems. These two probes are synthesized by PCR: one is labelled with fluorescein and the other with digoxigenin. The former is detected by chemiluminescence and the latter by colorimetry. We applied this rapid and simple method to the specific detection of multiplex polymerase chain reaction products. We used the human herpes simplex virus HSV1 and HSV2 PCR models studied in our laboratory. PMID- 7877637 TI - Comparison of genus- and species-specific probes for PCR detection of mycobacterial infections. AB - We describe experiments comparing use of different DNA probes to detect mycobacteria in clinical specimens after PCR. The objective was to assess correlation between results using Mycobacterium genus-specific, and species specific M. tuberculosis probes. Given sufficient concordance, sequential use of such probes would provide a useful screening tool. An evaluation of genus specific probes compared use of repetitive sequences in the clone pMAv17 with the 65-kDa sequences. Sensitivity was 100% for pMAv17, 93% using the 65-kDa sequence; specificity was 70% for both. We then compared M. tuberculosis-specific probes developed by us (Tb400) with IS6110 and mpt40. Sensitivity using Tb400 was 100%; using IS6110 was 97%, and using mpt40 was 50%. Specificity using Tb400 and IS6110 was 68%, and was 70% using mpt40. Fourteen specimens which were PCR-positive and culture-negative, were positive using both genus probes, and the M. tuberculosis specific probes Tb400, and IS6110. Ten of these were positive using mpt40. PMID- 7877639 TI - Phenol extraction revisited: a rapid method for the isolation and preservation of human genomic DNA from whole blood. AB - We report a fast and simple DNA isolation method from whole blood. It avoids cell separation and lysis steps and consists of three successive solvent extractions and an ethanol precipitation. All the steps are carried out at room temperature. The main advantage of this method is the immediate sample inactivation achieved by mixing the blood sample with Tris-HCl (pH 8.0) saturated phenol, thus minimizing the biohazard involved in the subsequent manipulation of the samples potentially contaminated with infectious agents (the procedure has been called SP for 'straight phenol'). In addition, extensive field sample collections are facilitated by the fact that the SP procedure can be stopped right after the simple manipulation of mixing the blood sample with the phenol; neither freezing nor refrigeration of the sample proved to be required. At this stage, the nucleases as well as infectious agent are inactivated and the rest of the protocol can wait to be carried out in the laboratory. In fact, the DNA preparation can be resumed after prolonged storage of the blood-phenol mix (up to 72 days has been checked in our laboratory) at room temperature without affecting the yield. The SP protocol may be scaled up, when large quantities of DNA are needed, or scaled down to smaller volumes, such as fingerprick blood samples. PMID- 7877638 TI - Single polymerase chain reaction for the detection of tetracycline-resistant determinants Tet K and Tet L. AB - Oligonucleotide primers were used in polymerase chain reaction assays to detect tetracycline-resistant determinants Tet K and Tet L. Forty-three isolates representing 11 genera carrying Tet K and/or Tet L determinants gave appropriate PCR products. The PCR products hybridized with labelled Tet K or Tet L probes, and differentiated the Tet K from the Tet L PCR products. We confirmed that two Haemophilus aphrophilus carried the Tet K determinant and two Veillonella parvula carried the Tet L determinant. This is the first time that either of these two genes have been found in Gram-negative species. Four vaginal samples, previously positive with the Tet M/O PCR assay, were also positive with the Tet K/L assay. This is the first report of a PCR assay for the detection of Tet K and Tet L determinants in bacteria or clinical specimens. PMID- 7877640 TI - Molecular cloning and nucleic acid sequencing of Chlamydia trachomatis 16S rRNA genes from patient samples lacking the cryptic plasmid. AB - We have examined the relationship between Chlamydia trachomatis found in clinical samples in which the cryptic plasmid was absent and known serovars of C. trachomatis. PCR and RNase protection assays were used to compare 12 C. trachomatis serovars and a plasmidless L2 serovar strain with the reactivity of clinical specimens taken from patients with pelvic inflammatory disease (PID) containing the C. trachomatis 16S rRNA gene and 16S rRNA but lacking plasmid DNA. Serovars D, E, H and I were unreactive in either or both of the PCR and RNase protection assays. The plasmidless L2 strain had reactivities indistinguishable from the nucleic acids found in the PID clinical specimens. Serovar D, the plasmidless L2 strain, and nucleic acids from two of the PID specimens were further compared by amplifying, cloning and sequencing the 16S rRNA genes detected in these samples. The sequences of the 16S rRNA genes detected in the PID clinical samples and the 16S rRNA gene of the plasmidless C. trachomatis variant were indistinguishable from previously reported sequences of the C. trachomatis 16S rRNA. Serovar D showed five base changes over the same region. We conclude that although these clinical samples lack the C. trachomatis cryptic plasmid, they do contain C. trachomatis nucleic acid. PMID- 7877641 TI - Young children's knowledge about thinking. PMID- 7877642 TI - Genetic toxicology of vinyl chloride--a review. AB - Vinyl chloride (VC) is a colorless gas with a mild, sweet odor. It is extensively used in the production of vinyl chloride polymer, copolymer resin, packaging materials, wire and cable coatings as well as in industrial and laboratory intermediates. It is toxic and also carcinogenic in experimental animals. The wide human exposure to this compound in different industries throughout the world causes great concern for human health. In the present review an attempt has been made to evaluate and update the genotoxic effects of vinyl chloride based on the available literature. PMID- 7877643 TI - In vivo short-term assays for tumor initiation and promotion in the glandular stomach of Fischer rats. AB - Here we summarize the data on 55 compounds tested in in vivo short-term assays for tumor-initiating and tumor-promoting activity in the glandular stomach of male Fischer (F344) rats. Most of the data has been previously published. Tumor initiating activity was assayed by measuring the induction of unscheduled DNA synthesis (UDS) and DNA single strand scission; tumor-promoting activity was assayed by measuring the induction of ornithine decarboxylase (ODC) activity, increased replicative DNA synthesis (RDS), and of c-fos and c-myc oncogene expression. The compounds were orally administered. Twenty-nine compounds were tested for UDS. Eight were positive, including 5 glandular stomach carcinogens; 16 were negative, including 5 liver carcinogens; and 5 were equivocal. Twenty compounds were tested for DNA single strand scission. Twelve were positive, including 6 glandular stomach carcinogens; 7 negative, including 2 liver carcinogens; and 1 was equivocal. Thirty-two compounds were tested for RDS. Twenty-six were positive, including 8 glandular stomach carcinogens and 6 glandular stomach tumor-promoters; 4 were negative, including 3 liver carcinogens and a stomach irritant; and 2 were equivocal. Forty-five compounds were tested for ODC. Thirty-seven were positive, including 8 glandular stomach carcinogens and 6 glandular stomach tumor promoters; 7 were negative, including 3 liver carcinogens; and one was equivocal. All glandular stomach carcinogens and tumor promoters examined were positive in both RDS and ODC. Two compounds were tested for c-fos and c-myc expression; one was a glandular stomach carcinogen and one was a glandular stomach tumor promoter, and both were positive. In addition, 2 compounds inhibited the increase in RDS induced by the tumor promoter NaCl, suggesting anti-tumor-promoter activity. Thus these assays are useful for assessing potential tumor-initiating and tumor-promoting activity in the rat glandular stomach. PMID- 7877644 TI - The comet assay: a comprehensive review. AB - The comet assay is a sensitive and rapid method for DNA strand break detection in individual cells. Its use has increased significantly in the past few years. This paper is a review of the studies published to date that have made use of the comet assay. The principles of strand break detection using both the alkaline and neutral versions of the technique are discussed, and a basic methodology with currently used variations is presented. Applications in different fields are reviewed and possible future directions of the technique are briefly explored. PMID- 7877645 TI - Effects of benzofuran and seven benzofuran derivatives including four carbamate insecticides in the in vitro porcine brain tubulin assembly assay and description of a new approach for the evaluation of the test data. AB - The influence of benzofuran and 7 benzofuran derivatives, including the carbamate insecticides benfuracarb, carbofuran, carbosulfan, and furathiocarb, on the in vitro assembly kinetics of porcine brain tubulin was investigated. A new approach to the evaluation of the raw data was made based on polynomial regression and the calculation of a polynomial function of the 11th degree fitting the raw data. By this procedure it is possible to calculate the parameters defining the shape of the absorbance curves and more parameters than those used so far can be included in the analysis of substance effects. In detail, the following curve parameters of the dependence of optical absorption on time were included in the evaluation of the substances of interest: the difference between maximum and minimum absorbance as a measure for the polymerization degree, the coordinates of the turning point of the curve, the slope of the tangent at the turning point which represents the maximum reaction velocity, the mean slope between the points with 10% absorbance increase and 90% absorbance increase and the duration of the lag phase. Out of the eight compounds tested, only the carbamate insecticides had distinct effects on the in vitro polymerization of tubulin, whereas benzofuran and the three 2,3-dihydro-2,2-dimethylbenzofuran derivatives without a carbamate function were inactive. Benfuracarb, carbofuran, carbosulfan, and furathiocarb led to a dose-dependent reduction of the polymerization degree of tubulin as well as to reduction of the maximum and mean reaction velocities. The strongest effects were obtained with furathiocarb and benfuracarb. PMID- 7877646 TI - Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. AB - BACKGROUND: Adjuvant combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil was administered after radical mastectomy for primary breast cancer with histologically positive axillary lymph nodes to assess whether it would improve treatment outcome as compared with surgery alone. Here we report a 20-year follow-up of this investigation. METHODS: In 1973 we began a trial involving 386 women who were randomly assigned to receive either no further treatment after radical mastectomy (179 women) or 12 monthly cycles of adjuvant combination chemotherapy (207 women). All patients were admitted to the Istituto Nazionale Tumori in Milan, Italy. Adjuvant chemotherapy was delivered in the outpatient clinic of the Division of Medical Oncology. RESULTS: After a median follow-up of 19.4 years, the patients given adjuvant combination chemotherapy had significantly better rates of relapse-free survival (unadjusted relative risk of relapse, 0.71; 95 percent confidence interval, 0.56 to 0.90; P = 0.004; adjusted relative risk, 0.65, 95 percent confidence interval, 0.51 to 0.83; P < 0.001) and total survival (unadjusted relative risk of death, 0.78; 95 percent confidence interval, 0.62 to 0.99; P = 0.04; adjusted relative risk, 0.76; 95 percent confidence interval, 0.60 to 0.97; P = 0.03). With the exception of postmenopausal women, a benefit from adjuvant chemotherapy was evident in all subgroups of patients. CONCLUSIONS: The long-term results of this trial of adjuvant combination chemotherapy confirm our preliminary observations of the effectiveness of the treatment in women with node-positive breast cancer. PMID- 7877647 TI - Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer. AB - BACKGROUND: Breast-conservation therapy for early-stage breast cancer is now an accepted treatment, but there is still controversy about its comparability with mastectomy. Between 1979 and 1987, the National Cancer Institute conducted a randomized, single-institution trial comparing lumpectomy, axillary dissection, and radiation with mastectomy and axillary dissection for stage I and II breast cancer. We update the results of that trial after a median potential follow-up of 10.1 years. METHODS: Two hundred forty-seven patients with clinical stage I and II breast cancer were randomly assigned to undergo either modified radical mastectomy or lumpectomy, axillary dissection, and radiation therapy. The 237 patients who actually underwent randomization have been followed for a median of 10.1 years. The primary end points were overall survival and disease-free survival. RESULTS: At 10 years overall survival was 75 percent for the patients assigned to mastectomy and 77 percent for those assigned to lumpectomy plus radiation (P = 0.89). Disease-free survival at 10 years was 69 percent for the patients assigned to mastectomy and 72 percent for those assigned to lumpectomy plus radiation (P = 0.93). The rate of local regional recurrence at 10 years was 10 percent after mastectomy and 5 percent after lumpectomy plus radiation (P = 0.17) after recurrences successfully treated by mastectomy were censored from the analysis. CONCLUSIONS: In the management of stage I and II breast cancer, breast conservation with lumpectomy and radiation offers results at 10 years that are equivalent to those with mastectomy. PMID- 7877648 TI - Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. AB - BACKGROUND: A specific point mutation in the gene coding for coagulation factor V is associated with resistance to degradation by activated protein C, a recently described abnormality of coagulation that may be associated with an increased risk of venous thrombosis. Whether this mutation also predisposes patients to arterial thrombosis is unknown, as is the value of screening for the mutation in order to define the risk of venous thrombosis among unselected healthy people. METHODS: Among 14,916 apparently healthy men in the Physicians' Health Study who provided base-line blood samples, 374 had myocardial infarctions, 209 had strokes, and 121 had deep venous thrombosis, pulmonary embolism, or both, during a mean follow-up of 8.6 years. We determined whether a mutation at nucleotide position 1691 of the factor V gene was present or absent in these 704 men and in an equal number of matched participants who remained free of vascular disease. RESULTS: The prevalence of heterozygosity for the mutation among men who had myocardial infarctions (6.1 percent, P = 0.9) or strokes (4.3 percent, P = 0.4) was similar to that among men who remained free of vascular disease (6.0 percent). However, the prevalence of the mutation was significantly higher among men who had venous thrombosis, pulmonary embolism, or both (11.6 percent, P = 0.02). In adjusted analyses, the relative risk of venous thrombosis among men with the mutation was 2.7 (95 percent confidence interval, 1.3 to 5.6; P = 0.008). This increased risk was seen with primary venous thrombosis (relative risk, 3.5; 95 percent confidence interval, 1.5 to 8.4; P = 0.004) but not with secondary venous thrombosis (relative risk, 1.7; 95 percent confidence interval, 0.6 to 5.3; P = 0.3), and it was most apparent among older men. Specifically, the prevalence of the mutation among men over the age of 60 in whom primary venous thrombosis developed was 25.8 percent (relative risk, 7.0; 95 percent confidence interval, 2.6 to 19.1; P < 0.001). CONCLUSIONS: In a large cohort of apparently healthy men, the presence of a specific point mutation in the factor V gene was associated with an increased risk of venous thrombosis, particularly primary venous thrombosis. The presence of the mutation was not associated with an increased risk of myocardial infarction or stroke. This mutation appears to be the most common inherited factor thus far recognized that predisposes patients to venous thrombosis. PMID- 7877649 TI - Iron-chelation therapy with oral deferiprone in patients with thalassemia major. AB - BACKGROUND: To determine whether the orally active iron chelator deferiprone (1,2 dimethyl-3-hydroxy-pyridin-4-one) is efficacious in the treatment of iron overload in patients with thalassemia major, we conducted a prospective trial of deferiprone in 21 patients unable or unwilling to use standard chelation therapy with parenteral deferoxamine. METHODS: Hepatic iron stores were determined yearly by chemical analysis of liver-biopsy specimens or magnetic-susceptibility measurements. Detailed clinical and laboratory studies were used to monitor safety and compliance. RESULTS: The patients received deferiprone therapy for a mean (+/-SE) of 3.1 +/- 0.3 years. Ten patients in whom previous chelation therapy with deferoxamine had been ineffective had initial hepatic iron concentrations of at least 80 mumol per gram of liver, wet weight -- values associated with complications of iron overload. Hepatic iron concentrations decreased in all 10 patients, from 125.3 +/- 11.5 to 60.3 +/- 9.6 mumol per gram (P < 0.005), with values that were less than 80 mumol per gram in 8 of the 10 patients (P < 0.005). In all 11 patients in whom deferoxamine therapy had previously been effective, deferiprone maintained hepatic iron concentrations below 80 mumol of iron per gram. CONCLUSIONS: Oral deferiprone induces sustained decreases in body iron to concentrations compatible with the avoidance of complications from iron overload. The risk of agranulocytosis associated with deferiprone may restrict its administration to patients who are unable or unwilling to use deferoxamine. PMID- 7877650 TI - Images in clinical medicine. Cerebral arteriovenous malformation. PMID- 7877651 TI - Primary sclerosing cholangitis. PMID- 7877652 TI - Seminars in medicine of the Beth Israel Hospital, Boston. Dementia associated with the acquired immunodeficiency syndrome. PMID- 7877653 TI - Jumping genes. PMID- 7877654 TI - Paradigmatic shifts in the management of breast cancer. PMID- 7877655 TI - An orally active iron chelator. PMID- 7877656 TI - Telomeres, cancer, and immortality. PMID- 7877657 TI - p53 and bladder cancer. PMID- 7877658 TI - p53 and bladder cancer. PMID- 7877659 TI - Severe adverse cutaneous reactions to drugs. PMID- 7877660 TI - Severe adverse cutaneous reactions to drugs. PMID- 7877661 TI - Severe adverse cutaneous reactions to drugs. PMID- 7877662 TI - Fluoxetine. PMID- 7877663 TI - Fluoxetine. PMID- 7877664 TI - Effect of the dialysis membrane in acute renal failure. PMID- 7877665 TI - Photopheresis for chronic rejection of lung allografts. PMID- 7877666 TI - Cost of HIV testing in the U.S. Army. PMID- 7877667 TI - What research results should the public believe? PMID- 7877668 TI - Parse analysis II. A revised model that accounts for phi. PMID- 7877669 TI - Republicans and the new politics of health care. PMID- 7877670 TI - Europe's parliament loses reputation. PMID- 7877671 TI - European Parliament rejects bid to stem confusion over gene patents. PMID- 7877672 TI - Blood warning 'urgent' says Canadian judge. PMID- 7877673 TI - Concern raised over US plan for A-bomb survivor studies. PMID- 7877674 TI - Roche asked for more Taq patent evidence. PMID- 7877675 TI - University blocks efforts to reveal researchers' identity. PMID- 7877676 TI - Impact of behavioural ecology. PMID- 7877677 TI - Retinoblastoma protein. Pol I gets repressed. PMID- 7877678 TI - Endocytosis. Ringing necks with dynamin. PMID- 7877679 TI - Transcriptional regulation. Cyclins in initiation. PMID- 7877680 TI - Ferromagnetism and EMFs. PMID- 7877681 TI - Another obese gene function. PMID- 7877682 TI - Recombination in HIV-1. PMID- 7877683 TI - Altered stress response in testis. PMID- 7877684 TI - Principles of CDK regulation. AB - As key regulators of the cell cycle, the cyclin-dependent kinases must be tightly regulated by extra- and intracellular signals. The activity of cyclin-dependent kinases is controlled by four highly conserved biochemical mechanisms, forming a web of regulatory pathways unmatched in its elegance and intricacy. PMID- 7877685 TI - The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins. AB - Heart rate is slowed in part by acetylcholine-dependent activation of a cardiac potassium (K+) channel, IKACh. Activated muscarinic receptors stimulate IKACh via the G-protein beta gamma-subunits. It has been assumed that the inwardly rectifying K(+)-channel gene, GIRK1, alone encodes IKACh. It is now shown that IKACh is a heteromultimer of two distinct inwardly rectifying K(+)-channel subunits, GIRK1 and a newly cloned member of the family, CIR. PMID- 7877686 TI - Antibody catalysis of a reaction otherwise strongly disfavoured in water. AB - Several examples have been reported recently of antibody catalysis of reactions that are strongly disfavoured because of the high free energy of the transition state. Here we show that catalytic antibodies can be used to promote a particularly useful kind of reaction from a synthetic point of view: one involving an intermediate that is highly unstable in water. We show that an antibody elicited against the quaternary ammonium ion 4a (Fig. 1) catalyses the protonation of the enol ether 1 to form, with complete enantioselectivity, an oxocarbonium intermediate. This species is highly reactive in water, and would normally react with a water molecule to give the corresponding ketone 2. But the antibody provides a hydrophobic environment that allows the oxocarbonium ion instead to undergo an intramolecular reaction to form an enantiomerically pure ketal 3. This result shows that catalytic antibodies can exclude solvent molecules entirely from crucial steps on the reaction pathway. PMID- 7877687 TI - Heritability of a sexually selected character expressed in both sexes. AB - Sexual selection is thought to be responsible for the evolution of exaggerated male characters and of female mate preferences. Evolutionary mechanisms driven by an advantage to the progeny are only effective if the preferred character has a large genetic component of variance; in most systems in which sexual selection operates, little is known of the relevant genetics. We have measured parent offspring correlations, and report here that the preferred character (adult size) in seaweed flies has large additive genetic variance in males, but not in females. Virtually all the variance in male size is attributable to a chromosomal inversion system and, consequently, because this system is also a major determinant of larval viability, male size could be used by females as a reliable indicator of offspring survival. PMID- 7877688 TI - Fasciclin III as a synaptic target recognition molecule in Drosophila. AB - Fasciclin III, a cell adhesion molecule of the immunoglobulin superfamily, is expressed by motor neuron RP3 and its synaptic targets (muscle cells 6 and 7) during embryonic neuromuscular development of Drosophila. We report here that RP3 often incorrectly innervates neighbouring non-target muscle cells when these cells misexpress fasciclin III, but still innervates normal targets in the fasciclin III null mutant. Fasciclin III manipulations do not influence target selections by other motor neurons, including fasciclin III-expressing RP1. We propose that fasciclin III acts as a synaptic target recognition molecule for motor neuron RP3, and also that its absence can be compensated for by other molecule(s). PMID- 7877689 TI - A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks. AB - Immunoglobulin and T-cell receptor (TCR) molecules are central to the adaptive immune system. Sequence conservation, similarities in domain structure, and usage of similar recombination signal sequences and recombination machinery indicate that there was probably a time during evolution when an ancestral receptor diverged to the modern-day immunoglobulin and TCR. Other molecules that undergo rearrangement have not been described in vertebrates, nor have intermediates been identified that have features of both these gene families. We report here the isolation of a new member of the immunoglobulin superfamily from the nurse shark, Ginglymostoma cirratum, which contains one variable and five constant domains and is found as a dimer in serum. PMID- 7877690 TI - ATP-dependent inositide phosphorylation required for Ca(2+)-activated secretion. AB - Regulated fusion of secretory granules with the plasma membrane in secretory cells requires ATP, Ca2+ and cytosolic as well as membrane proteins. ATP dependent steps in Ca(2+)-activated secretion from PC12 cells require three cytosolic PEP proteins (priming in exocytosis proteins, PEP1-3), the identity of which will provide insights into the required ATP-using reactions. PEP3 was recently identified as phosphatidylinositol transfer protein (PtdInsTP), and here we report that PEP1 consists of the type I phosphatidylinositol-4-phosphate 5 kinase (PtdInsP5K). The roles of PEP3/PtdInsTP and PEP1/PtdInsP5K in sequential phosphoinositide recruitment and phosphorylation explains their synergistic activity in ATP-dependent priming. Moreover, inhibition of Ca(2+)-activated secretion by PtdIns(4,5)P2-specific antibodies and phospholipase C implies that 5 phosphorylated inositides play a novel, necessary role in the regulated secretory pathway. The results indicate that lipid kinase-mediated phosphorylation is an important basis for ATP use in the exocytotic pathway. PMID- 7877691 TI - Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product. AB - The protein encoded by the retinoblastoma susceptibility gene (Rb) functions as a tumour suppressor and negative growth regulator. As actively growing cells require the ongoing synthesis of ribosomal RNA, we considered that Rb might interact with the ribosomal DNA transcription apparatus. Here we report that (1) there is an accumulation of Rb protein in the nucleoli of differentiated U937 cells which correlates with inhibition of rDNA transcription; (2) addition of Rb to an in vitro transcription system inhibits transcription by RNA polymerase I; (3) this inhibition requires a functional Rb pocket; and (4) Rb specifically inhibits the activity of the RNA polymerase I transcription factor UBF (upstream binding factor) in vitro. This last observation was confirmed by affinity chromatography and immunoprecipitation, which demonstrated an interaction between Rb and UBF. These results indicate that there is an additional mechanism by which Rb suppresses cell growth, namely that Rb directly represses transcription of the rRNA genes. PMID- 7877692 TI - A structural basis of the interactions between leucine-rich repeats and protein ligands. AB - The leucine-rich repeat is a recently characterized structural motif used in molecular recognition processes as diverse as signal transduction, cell adhesion, cell development, DNA repair and RNA processing. We present here the crystal structure at 2.5 A resolution of the complex between ribonuclease A and ribonuclease inhibitor, a protein built entirely of leucine-rich repeats. The unusual non-globular structure of ribonuclease inhibitor, its solvent-exposed parallel beta-sheet and the conformational flexibility of the structure are used in the interaction; they appear to be the principal reasons for the effectiveness of leucine-rich repeats as protein-binding motifs. The structure can serve as a model for the interactions of other proteins containing leucine-rich repeats with their ligands. PMID- 7877693 TI - Tubular membrane invaginations coated by dynamin rings are induced by GTP-gamma S in nerve terminals. AB - The mechanisms through which synaptic vesicle membranes are reinternalized after exocytosis remain a matter of debate. Because several vesicular transport steps require GTP hydrolysis, GTP-gamma S may help identify intermediates in synaptic vesicle recycling. In GTP-gamma S-treated nerve terminals, we observed tubular invaginations of the plasmalemma that were often, but not always, capped by a clathrin-coated bud. Strikingly, the walls of these tubules were decorated by transverse electron-dense rings that were morphologically similar to structures formed by dynamin around tubular templates. Dynamin is a GTPase implicated in synaptic vesicle endocytosis and here we show that the walls of these membranous tubules, but not their distal ends, were positive for dynamin immunoreactivity. These findings demonstrate that dynamin and clathrin act at different sites in the formation of endocytic vesicles. They strongly support a role for dynamin in the fission reaction and suggest that stabilization of the GTP-bound conformation of dynamin leads to tubule formation by progressive elongation of the vesicle stalk. PMID- 7877694 TI - Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding. AB - DYNAMIN, a 100K member of the GTPase superfamily, is the mammalian homologue of the Drosophila shibire gene product. Mutations in shibire cause a defect in endocytosis leading to accumulation of coated pits and deep invaginations at the plasma membrane of all tissues examined. Similarly, invaginated coated pits accumulate in mammalian cells overexpressing dominant-negative mutants of dynamin, establishing that dynamin is required for the formation of 'constricted' coated pits and for coated vesicle budding. Whether dynamin functions in the classic GTPase mode as a molecular switch to regulate events leading to coated vesicle budding or instead actively participates as a mechanochemical enzyme driving coated vesicle formation is unclear. Here we show that dynamin spontaneously self-assembles into rings and stacks of interconnected rings, comparable in dimension to the 'collars' observed at the necks of invaginated coated pits that accumulate at synaptic terminals in shibire flies. We propose that invaginated coated pits become constricted by the assembly of dynamin into rings around their necks. A concerted conformational change would then close the rings and pinch off the budding coated vesicles. PMID- 7877695 TI - A kinase-cyclin pair in the RNA polymerase II holoenzyme. AB - The RNA polymerase II holoenzyme consists of RNA polymerase II, a subset of general transcription factors, and regulatory proteins known as SRB proteins. The genes encoding SRB proteins were isolated as suppressors of mutations in the RNA polymerase II carboxy-terminal domain (CTD). The CTD and SRB proteins have been implicated in the response to transcriptional regulators. We report here the isolation of two new SRB genes, SRB10 and SRB11, which encode kinase- and cyclin like proteins, respectively. Genetic and biochemical evidence indicates that the SRB10 and SRB11 proteins form a kinase-cyclin pair in the holoenzyme. The SRB10/11 kinase is essential for a normal transcriptional response to galactose induction in vivo. Holoenzymes lacking SRB10/11 kinase function are strikingly deficient in CTD phosphorylation. Although defects in the kinase substantially affect transcription in vivo, purified holoenzymes lacking SRB10/11 kinase function do not show defects in defined in vitro transcription systems, suggesting that the factors necessary to elicit the regulatory role of the SRB10/11 kinase are missing in these systems. These results indicate that the SRB10/11 kinase is involved in CTD phosphorylation and suggest that this modification has a role in the response to transcriptional regulators in vivo. PMID- 7877696 TI - [Bone pain in patients with cancer is not always due to bone metastasis]. PMID- 7877697 TI - [Are supplemental studies always a supplement?]. PMID- 7877698 TI - [Esophageal echocardiography; indications and diagnostic results]. PMID- 7877699 TI - [One antibody preparation is not another: the role of passive immunotherapy in the treatment of HIV infection]. PMID- 7877700 TI - [Entering of patients in clinical-oncological trials: why not exclusive exclusion when inclusion is out of the question?]. PMID- 7877701 TI - [Underestimation of intestinal protozoa as a cause of diarrhea in family practice]. AB - OBJECTIVE: To assess the frequency of intestinal protozoa in stool samples of patients with diarrhoea in general practice. SETTING: General practitioners' laboratory in Haarlem, Netherlands. DESIGN: Descriptive study. METHOD: During one year (1 February 1992 to 31 January 1993) all stool samples from patients with diarrhoea visiting a general practitioner were examined according to a standard protocol consisting of bacterial and protozoal examination. RESULTS: Among 1703 stool examinations requested by general practitioners and performed according to the protocol, pathogenic protozoa were found in 10.8% and pathogenic bacteria in 8.6%. Of the 184 patients who tested positive for pathogenic protozoa 156 harboured Giardia lamblia, 22 Entamoeba histolytica and 6 Cryptosporidium spp. Pathogenic protozoa were predominantly found in patients with diarrhoea persisting for longer than 1 week and in cases with intermittent diarrhoea. In patients with acute diarrhoea (duration < 1 week) we predominantly found pathogenic bacteria (Campylobacyter jejuni). If the search for protozoa in the stool samples would not have been performed routinely, 34% of the pathogenic protozoa (Giardia lamblia) would not have been found. CONCLUSION: Intestinal infections with protozoa are not rare in general practice. It seems worthwhile to perform protozoal examination of the stool samples in case of persistent diarrhoea. PMID- 7877702 TI - [Good results in early mobilization following reconstruction of the anterior cruciate ligament]. PMID- 7877703 TI - [Trans-esophageal contrast echocardiography in suspicion of paradoxal embolism]. AB - In two patients, women of 35 and 74 years old, paradoxical embolism was diagnosed. Patient A presented with multiple pulmonary embolism. Transoesophageal echocardiography demonstrated a thrombus mass which protruded from the right atrium through a patent foramen ovale into the left atrium: explicit proof of the possibility of paradoxical embolism. Patient B presented with systemic arterial embolism. During hospitalisation multiple pulmonary embolism occurred. With the use of transoesophageal contrast echocardiography a patent foramen ovale was observed, the probable cause of paradoxical embolism. Both patients were treated with intravenous heparin and oral anticoagulants. PMID- 7877704 TI - [Atrial septal aneurysm and brain infarct: a causal connection?]. AB - In four patients, 2 women aged 24 and 35 and 2 men aged 37 and 47 years, an ischaemic stroke was observed and an atrial septal aneurysm was found as a possible cardiac source of embolism to the brain. Atrial septal aneurysm is a bulging of the fossa ovalis region, that can be visualised by (preferably transoesophageal) echocardiography. In the four patients there were only few other risk factors for ischaemic stroke (migraine, smoking, oral contraceptives). Cerebral angiography was normal in all cases. Recent literature suggests that a causal relationship exists between atrial septal aneurysm and ischaemic stroke. It is still uncertain what treatment is best. PMID- 7877705 TI - [Supportive care]. PMID- 7877706 TI - [Belt and suspenders. Medical jargon in The Netherlands and Flanders]. PMID- 7877707 TI - Ventilator-associated pneumonia: do the bacteria come from the stomach? PMID- 7877709 TI - Phagocytic plasma cells in a patient with multiple myeloma. AB - Phagocytosis of blood cells by malignant plasma cells in multiple myeloma is an extremely rare condition. Here we present a 39-year-old woman with multiple myeloma. Bone marrow smear showed an extensive phagocytosis of erythrocytes and platelets by myeloma cells. PMID- 7877710 TI - Recurrent hepatic pre-coma resulting from a spontaneous porto-spleno-renal shunt (PSRS). AB - A 64-year-old Turkish male is described with recurrent hepatitic (pre-)coma resulting from a spontaneous porto-spleno-renal shunt, portal hypertension and hepatic insufficiency. In cases of chronic encephalopathy resulting from hepatic insufficiency that may be due to liver cirrhosis, the presence of a spontaneous porto-spleno-renal shunt should be considered as a distinct possibility, not only in the absence of apparent oesophageal varices and splenomegaly, but also when there is hepatopetal flow in the portal vein. PMID- 7877708 TI - Once-daily antihypertensive treatment with calcium antagonists: utopia or reality? AB - Although a large number of antihypertensive drugs have been approved for once- or twice-daily dosing, no standardized set of evidence is required to demonstrate that the blood pressure reduction is sustained for 24 h. The recent literature on calcium antagonists was therefore searched for the arguments usually put forward to objectify a long duration of action. Most studies relied on ambulatory blood pressure monitoring. However, several published reports were difficult to interpret for a variety of reasons, such as: (1) a non-blinded non-randomized study design; (2) a statistical analysis, which was discordant with the study design; (3) analyses confined to the 24 h, day-time and night-time pressure means; (4) the absence of a baseline adjustment and/or formal statistical testing; (5) the "post hoc" subdivision of patients into responders and non responders; and (6) the absence of a well-specified time-frame linking drug intake to the observed antihypertensive effects. According to the authors' interpretation, amlodipine, diltiazem SR (modified release), felodipine SR, isradipine SR, nifedipine SR, nitrendipine and verapamil SR have all been confirmed to reduce both the conventional and the 24 h blood pressure. Some studies went beyond the 24 h blood pressure means and also presented separate results for the day-time (or awake) and night-time (or sleeping) periods, or investigated the blood pressure reduction at the end of the dosing interval, or compared the diurnal blood pressure profiles on different treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877711 TI - Pulmonary infarction caused by giant-cell arteritis of the pulmonary artery. AB - A 79-year-old woman presented with a pulmonary infarction concurrent with a relapse of giant-cell arteritis during tapering off of prednisone. As no origin for thromboembolism could be found, it is very probable that the thrombosis of the branch of the pulmonary artery was superimposed on local giant-cell vasculitis. Rapid clinical and laboratory recovery was achieved with anticoagulant therapy and by increasing the prednisone dosage. The literature on this rare manifestation of giant-cell arteritis is reviewed. PMID- 7877712 TI - Treatment of proliferative lupus nephritis with methylprednisolone pulse therapy and oral azathioprine. AB - OBJECTIVE: To evaluate the treatment of proliferative lupus nephritis with methylprednisolone pulse therapy and oral azathioprine. PATIENTS AND METHODS: Eighteen patients with severe proliferative lupus nephritis (Class III, IV or Vd according to criteria of the World Health Organization) were treated with intravenous methylprednisolone (MP) pulse therapy in combination with a low oral maintenance dose of prednisone (20 mg) and azathioprine (2 mg/kg). Thirteen patients (Group I) had a recent onset of clinical manifestations of nephritis at referral (mean and median 4 months). Five patients (Group II) had clinical signs of nephritis for a long time (median 4 years, mean 5 years) and were referred because of progressive renal failure. The mean plasma creatinine in Group I was 109 mumol/l with a mean GFR of 58 ml/min, the mean plasma creatinine in Group II was 284 mumol/l with a mean GFR of 12 ml/min. Renal histology in Group II was characterized by severe chronic damage (chronicity index 8-10). RESULTS: Short term and long-term effects of treatment were excellent in Group I. The mean plasma creatinine was 68 mumol/l with a mean GFR of 102 ml/min at a mean follow up of 7 years, median 4 years (range 1-15 years). All patients in Group II needed renal replacement therapy after a mean follow-up of 2.6 years, median 2 years (range 0-8 years). Major side-effects of treatment were only seen twice. CONCLUSION: Methylprednisolone pulse therapy in combination with low oral maintenance doses of prednisone and oral azathioprine is an effective and safe treatment for patients with severe active proliferative lupus nephritis. In patients with extensive irreversible lesions, this treatment has no or only a temporary effect. PMID- 7877713 TI - Peritonitis, moderate ascites and hepatitis due to infection with Chlamydia trachomatis and Epstein-Barr virus in a young woman. Diagnosis by polymerase chain reaction from peritoneal tissue. AB - Perihepatitis with ascites is a well-known presentation of pelvic inflammatory disease due to Chlamydia trachomatis. Diagnosis is based on the presence of IgM antibodies or positive culture from cervical samples or ascites. We describe a young woman with a concomitant infection of C. trachomatis and Epstein-Barr virus presenting with fever, hepatitis and ascites. Cultures remained negative and other tests were--at first--inconclusive. Diagnosis was ultimately established by polymerase chain reaction (PCR) and RNA in situ hybridisation of peritoneal tissue obtained at laparoscopy. PMID- 7877714 TI - Plasma lipoprotein abnormalities in type 1 (insulin-dependent) diabetes mellitus. AB - Lipoprotein abnormalities may well contribute to the increased risk of coronary heart disease, cerebrovascular disease and peripheral vascular disease observed in type 1 (insulin-dependent) diabetes mellitus. The spectrum of diabetes associated changes in lipoprotein metabolism is discussed. The plasma levels of lipoprotein cholesterol and triglycerides are largely influenced by the degree of glycaemic control. With poor metabolic control, plasma cholesterol and triglycerides are frequently elevated. In contrast, in well-regulated patients without micro- and macrovascular complications lipid levels are generally normal or even favourable, although lipoprotein composition abnormalities can persist despite intensified insulin treatment. With the development of diabetic nephropathy the cardiovascular risk increases markedly and this complication is associated with increased concentrations of cholesterol and of the atherogenic lipoprotein species, lipoprotein(a), and low levels of high-density lipoprotein cholesterol. The rationale for treatment of lipid disorders in diabetes mellitus is based upon results of trials conducted primarily in non-diabetic populations. It is hoped that with increased recognition of dyslipidaemia and aggressive therapeutic measures the overkill in diabetes mellitus from macrovascular diseases will be reduced. PMID- 7877715 TI - Presynaptic and postsynaptic effects of mercuric ions on guinea-pig ileum longitudinal muscle strip preparation. AB - The toxic effect of mercuric ions on intestinal cholinergic neurotransmission was investigated in vitro. Hg2+ inhibited the evoked release and enhanced the resting release of ACh. Smooth muscle contraction was irreversibly inhibited by Hg2+ in a concentration-dependent manner, and Na2EDTA did not antagonize this effect. We also investigated if Hg2+ enters the nerve terminal through Ca(2+)-channels, or Na(+)-channels, or both. The effects of mercuric ions obtained in our study were completely abolished by the combined administration of TTX and Co2+. It is suggested that the site of the action of mercuric ions is intracellular. We concluded that Hg2+ may interfere with cholinergic transmission by blocking [Ca2+]o-dependent release of ACh and by enhancing [Ca2+]o-independent resting release of ACh. The effect of Hg2+ was not only presynaptic since it also inhibited the effect of ACh on smooth muscle. PMID- 7877716 TI - Liposome-entrapped superoxide dismutase reduces ischemia/reperfusion 'oxidative stress' in gerbil brain. AB - Bilateral common carotid artery occlusion (15 min.) followed by two hours of recirculation reduced mitochondrial superoxide dismutase (SOD) and glutathione reductase (GR) activities, and increased susceptibility of mitochondrial membranes to in vitro lipid peroxidation in brain regions (i.e., cortex, striatum and hippocampus) of Mongolian gerbil. Intraperitoneal bolus injection (2 mg/kg b.w.) of liposome-entrapped CuZn superoxide dismutase (1-SOD) increased the endogenous SOD activity in normal brain tissue and, when given at the end of ischemia, counteracted both the ischemic reduction of endogenous SOD and the increased peroxidation of mitochondrial membranes. 1-SOD treatment was ineffective in reducing brain swelling, suggesting that superoxide radicals are not a main participant in the process of (post)ischemic brain edema formation. PMID- 7877717 TI - Generation of a monoclonal antibody against the myelin protein CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase) suitable for biochemical and for immunohistochemical investigations of CNP. AB - The functional role of CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase), a minor component of central and peripheral myelin is still unclear. Here we describe preparation of a monoclonal antibody directed against CNP. The antibody, of the immunoglobulin IgG1 type, raised with a basic 46 kDa membrane-associated protein solubilized from pig cerebellar membranes, can be used to detect immunoreactivity in solubilized brain homogenates from pig, mouse, rat, sheep, cow and man, in cerebrum and cerebellum, but not in other tissues such as liver, skeletal and heart muscle. The antibody recognizes the CNP doublet band and shows no cross-reactivity with any of the other brain proteins solubilized. In tissue sections from paraformaldehyde-fixed rat brain the antigen was localized in oligodendrocytes. In cultured glial cells from newborn mice the antibody stained cells which were identified as oligodendrocytes by co-localization of myelin basic protein. Even cells from a C6 rat glioma cell line, which contain very little of CNP, were labeled by the monoclonal antibody. Thus the monoclonal antibody recognizing CNP from several species is suitable for immunocytochemical investigations and also for biochemical studies of CNP, since the antibody has been employed for immunoprecipitation and immunopurification of CNP in crude brain homogenates. PMID- 7877718 TI - 3,4-dihydroxyphenylalanine (dopa) metabolism and retinoic acid induced differentiation in human neuroblastoma. AB - In mature cells of the sympathetic nervous system and the adrenal gland, the activity of dihydroxyphenylalanine decarboxylase (DDC) is higher than that of tyrosine hydroxylase and 3,4-dihydroxyphenylalanine (dopa) does not accumulate in the cells. On the other hand, it is known that in some neuroblastoma cells there is a relative deficiency of DDC, resulting in accumulation and secretion of dopa. Such a relative deficiency of DDC is a characteristic of neural cells at an early stage of neural crest development, suggesting the neuroblastoma are cells arrested in early neural crest development. If this were the case, it is possible that agents such as retinoic acid (RA) could induce neuroblastoma to differentiate into mature cells with respect to their metabolism of catecholamines. We have measured the effect of RA on the metabolism of dopa and expression of tyrosine hydroxylase and DDC in human neuroblastoma cell lines, CHP 126, CHP-134, IMR-32, NB-69, and LA-N-5. When the cell cultures were treated with RA, they showed wide variations in response as measured by morphological change, growth inhibition, enzyme activities and enzyme expressions. The RA treatment modulated the activities of tyrosine hydroxylase and DDC, but does not increase DDC relative to tyrosine hydroxylase. It is concluded that RA does not induce biochemical differentiation of the neuroblastoma into mature cells even when there are extensive morphological changes and suppression of growth rate. PMID- 7877720 TI - KB-2796, a calcium channel blocker, ameliorates ischemic spinal cord damage in rabbits. AB - The effect of the calcium channel blocker (KB-2796) on metabolic and functional recovery in rabbit spinal cord after 20, 30, and 40 min ischemia and 4 days of recovery was investigated. The drug was given intraperitoneally in three different doses, 10, 20, or 50 mg/kg pre- or post-ischemia of 20, 30, or 40 min duration. Both higher doses 20 and 30 mg/kg completely recovered energy state and significantly improved neurological functions in the spinal cord following 20 and 30 min ischemia. Partial protection was observed even after 40 min ischemia. The protective effect of KB-2796 exceeds the effect of calcium blockers previously used in experimental spinal cord ischemia. PMID- 7877719 TI - Neuroblast cell death in ovo and in culture: interaction of ethanol and neurotrophic factors. AB - We used two experimental paradigms to examine the influence of the neurotrophins, NGF, EGF, and bFGF on normal neuroblast survival and also after ethanol insult. In the first paradigm, chick embryos received in ovo at embryonic day 1 and 2 (E1 and E2) saline (control) ethanol (10mg/50 microliters/day), NGF (50 ng/50 microliters/day), or EGF (25 ng/50 microliters/day), or ethanol+NGF or EGF. At E3, cultures were prepared from whole embryos separately from each group. At C2, all cultures were labeled with [3H]thymidine and assessed for effects or neuronal survival. In the second paradigm, cultures were prepared from 3-day-old whole embryos and at C0, cultures were treated with either ethanol (50 mM) alone, NGF (50 ng/ml) alone, EGF (25 ng/ml) alone, bFGF (50 ng/ml) alone, or were treated concomitantly with ethanol plus one of the neurotrophins; control had only the culture medium, DMEM + 5% FBS. We obtained the following findings. 1) Cultures derived from embryos treated with either of the three neurotrophins exhibited a higher neuronal survival as compared to controls (1st paradigm). 2) The survival promoting effect was also observed when the neurotrophins were added directly to the cultures (2nd paradigm). 3) As reported previously, cultures derived from ethanol-treated embryos exhibited a marked decline in neuronal survival as compared to controls. 4) All three neurotrophins attenuated the decline in neuronal survival produced by ethanol. The 'rescuing' effects of the neurotrophins support our early hypothesis that ethanol administration during early neurogenesis interferes with microenvironmental trophic signals essential for neuroblast survival and differentiation. PMID- 7877721 TI - Disulfiram lowers Ca2+, Mg(2+)-ATPase activity of rat brain synaptosomes. AB - The chronic administration of disulfiram (DS) to rats resulted in significant decrease of synaptosomal Ca2+, Mg(2+)-ATPase activity. In vitro studies indicated that DS (ID50 = 20 microM) produced a dose-dependent inhibition of Ca2+, Mg(2+) ATPase. However, diethyldithio-carbamate, a metabolite of DS, failed to modify Ca2+, Mg(2+)-ATPase activity, implying that the decrease in ATPase activity in DS administered rats was due to the effect of parent compound. The DS-mediated inhibition (48%) of ATPase activity was comparable with a similar degree of inhibition (49%) achieved by treating the synaptosomal membranes with N ethylmaleimide (ID50 = 20 microM) in vitro. Furthermore, the inhibition by DS was neither altered by washing the membranes with EGTA nor reversed by treatment with sulfhydryl reagents such as GSH or dithiothreitol. About 74% and 68% decrease of synaptosomal Ca2+, Mg(2+)-ATPase specific activity was observed when treated with DS (30 microM) and EGTA (100 microM) respectively. The remaining 25-30% of total activity is suggested to be of Mg(2+)-dependent ATPase activity. This indicates that both these drugs may act on a common target, calmodulin component that represents 70-75% of total Ca2+, Mg(2+)-ATPase activity. Therefore, DS-mediated modulation of synaptosomal Ca2+, Mg(2+)-ATPase activity could affect its function of maintaining intracellular Ca2+ concentration. This could contribute to the deleterious effects on CNS. PMID- 7877722 TI - Volatile anesthetics inhibit NMDA-stimulated 45Ca uptake by rat brain microvesicles. AB - We have previously shown that volatile anesthetics inhibit glutamate-stimulated [3H]MK-801 binding to the ionophore of NMDA receptor complexes in rat brain. In the present study, we examined the influence of enflurane and halothane on NMDA stimulated 45Ca uptake by a microvesicle fraction isolated from rat brain. NMDA stimulated 45Ca uptake (30 sec) by rat brain microvesicles by up to 70% with an EC50 of 1.4 +/- 0.5 microM. The NMDA-stimulated 45Ca uptake was inhibited by MK 801 and D-AP-5 with IC50's of approximately 10 microM. Enflurane and halothane inhibited 45Ca uptake stimulated by 100 microM NMDA by as much as 60-80% with IC50's of 0.2-0.3 mM, concentrations achieved during routine clinical use. Basal 45Ca uptake measured in the absence of agonist was not affected by the anesthetics. Glycine did not affect the level of NMDA-stimulated 45Ca uptake, but markedly reduced the inhibition of uptake caused by enflurane and halothane. Preincubation of microvesicles with NMDA resulted in a desensitization of NMDA stimulated 45Ca uptake, with a t1/2 of approximately 20 sec. Enflurane and halothane diminished both the extent and rate of development of this desensitization, as did glycine. These findings support the idea that volatile anesthetic interference with neurotransmission at NMDA receptor complexes contributes to the development of the anesthetic state. PMID- 7877723 TI - Previous stress increases in vivo biogenic amine response to swim stress. AB - In vivo microdialysis was used to determine biogenic amines in medial prefrontal cortex of rats exposed to eight minutes of swim stress on two consecutive days. On the first day of stress, norepinephrine (NE) efflux increased by 183% over baseline after stress, while dopamine (DA) and serotonin (5-HT) remained stable throughout. On the second day of stress, a robust increase was observed in all 3 neurotransmitters measured, with (NE), (DA), and (5-HT) increasing by 310%, 441% and 496% respectively, and remaining elevated for an hour or more after stress. This suggests that the first exposure to swim stress, while not causing dramatic changes in biogenic amine release, may sensitize biogenic amines in medial prefrontal cortex to subsequent swim stress. Our results also serve as preliminary data concerning the neurochemical changes which might underlie the forced swimming model of "behavioral despair". PMID- 7877724 TI - Repeated electroconvulsive shock selectively increases the expression of the neuron specific enolase in piriform cortex. AB - The effect of repeated electroconvulsive shock (ECS) on the activities of the three enolase isoenzymes present in rat brain: neuron specific enolase (NSE), non neuronal enolase (NNE) and the hybrid enolase was investigated in piriform cortex. The activities were estimated on isoenzymes separated by agarose gel electrophoresis. Whereas the specific activities of NNE and hybrid enolase were unchanged in piriform cortex or ECS-treated rats the specific activity of NSE was increased by 16.3 percent (P < 0.02). The brain enolase isoenzymes are dimers of alpha- and gamma-enolase subunits. The calculated ratio between the gamma-subunit present in both NSE and hybrid enolase and the alpha-subunits present in both NNE and hybrid enolase was increased by 11.7 percent in piriform cortex of ECS treated rats (P < 0.05). Previously, it has been shown that the gamma-subunit is only expressed in neurons whereas the alpha-subunit is expressed in both neurons and glial cells. The selectively increased expression of the enolase gamma subunit in ECS-treated rats might either reflect an increased transcription of a whole group of neuronal genes or rather the trophic role of NSE in ECS-enhanced synaptic remodelling of the rat brain. PMID- 7877725 TI - H1(0) and H3.3B mRNA levels in developing rat brain. AB - Two overlapping rat cDNAs, covering a continuous region of 1107 base pairs, have been isolated and sequenced. The clones contain identical open reading frames, encoding a 136 amino acid long polypeptide which exhibits 100% identity to other mammalian H3.3 histone variants. We show that the inserts derive, in particular, from the H3.3B gene. We used these inserts and an insert from an H1(0) encoding clone, previously described (6), as probes to study the accumulation of mRNAs encoding the corresponding histone replacement variants (namely, H1(0) and H3.3) during rat brain development. We found that the concentration of both H1(0) and H3.3B mRNAs decreases from the embryonal day 18 (E18) to the postnatal day 10 (P10), with inverse correlation to protein accumulation. PMID- 7877726 TI - Decreased hippocampal noradrenaline does not affect corticosterone release following electrical stimulation of CA1 pyramidal cells. AB - Bipolar electrodes were implanted into the CA1 pyramidal cells of the dorsal hippocampus and the effect of electrical stimulation of these cells on corticosterone secretion was investigated in freely moving rats. Histology showed that the electrodes were positioned in close proximity to the CA1 pyramidal cells. Rats that were subjected to high intensity electrical stimulation (1, 10, and 100 microA) behaved differently when compared to their sham stimulated controls. They were more active and displayed wet dog shakes. Plasma corticosterone levels increased dose-dependently in rats subjected to different electrical stimulation intensities. Although prior treatment (24 hours) of rats with DSP4 (60 mg/kg, i.p.) significantly reduced hippocampal noradrenaline content by 46%, it did not bring about any behavioural changes. DSP4 treatment also had no effect on electrically stimulated corticosterone release. These data suggested that stimulation of CA1 pyramidal cells may lead to increased corticosterone release and that a decrease in hippocampal noradrenaline concentration was unable to alter this corticosterone response. PMID- 7877727 TI - Tunicamycin inhibits prostaglandin F2 alpha receptor-mediated phosphoinositide hydrolysis in cultured rat astrocytes. AB - Effect of tunicamycin, an inhibitor of N-linked glycosylation, on prostaglandin (PG) F2 alpha-stimulated phosphoinositide (PI) hydrolysis was examined in cultured rat astrocytes. Pretreatment of cultured astrocytes with tunicamycin (25 250 ng/ml) inhibited subsequent PGF2 alpha (1 microM)-stimulated PI-hydrolysis in concentration- and time-dependent manners. The inhibition completely recovered after removal of tunicamycin and re-incubation for 12 h. Tunicamycin pretreatment (100 ng/ml for 12 h) significantly blocked [35S]methionine incorporation into cultured astrocytes, but cell viability was not affected under the condition. Inhibitors of processing of N-linked sugar chains such as bromoconduritol, 1 deoxymannojirimycin, and swainsonine had no effect on PI response to PGF2 alpha. These observations suggest that PGF2 alpha receptor is N-linked glycosylated. PMID- 7877728 TI - Changes in non-synaptosomal and synaptosomal mitochondrial membrane-linked enzymatic activities after transient cerebral ischemia. AB - Non-synaptosomal and synaptosomal mitochondrial membrane-linked enzymatic activities, NADH-cytochrome c reductase rotenone insensitive (marker of the outer membrane) and cytochrome oxidase (marker of the inner membrane), were measured in rat brain hippocampus and striatum immediately after and 1, 4 and 7 days following the induction of complete transient ischemia (15 min) by the four vessel occlusion method. Furthermore citrate synthetase activity was measured with and without Triton X-100 in order to qualitatively evaluate the membrane permeability. Non-synaptosomal mitochondrial membranes showed reduction of both activities only in the late reperfusion phase: NADH-CCRRi decreased in striatal mitochondria after 4-7 days and only after 7 days in the hippocampus. COX activity decreased only in striatal mitochondria 7 days after ischemia. Non synaptosomal mitochondrial membrane permeability did not show changes. Synaptosomal mitochondria showed a decrease of NADH-CCRRi only at 7 days of reperfusion both in hippocampus and striatum, while COX activity decreased only during ischemia and returned to normal levels in the following days in the two areas considered. In summary, free mitochondria showed insensitiveness to ischemia but they resulted damaged in the late reperfusion phase, while mitochondria from the synaptic terminal showed ischemic damage, partially restored during reperfusion. The striatal mitochondria showed a major susceptibility to ischemia/reperfusion damage, showing changes earlier than the hippocampal ones. PMID- 7877730 TI - [Neuroendoscopic surgery]. PMID- 7877731 TI - [Percutaneous transluminal angioplasty for cervical carotid artery stenosis]. AB - Percutaneous transluminal angioplasty (PTA) was attempted in 16 patients (17 procedures) with cervical internal carotid artery (ICA) stenosis. Among the 16 patients, 14 were male and 2 were female aged from 44 to 76 years (average 63.4 years). One had cerebral infarction on the acute stage, and the other 15 were in the chronic stage. On CT scan and MRI, there were nine multiple lacunar infarctions and seven watershed infarctions. On angiographical findings, 13 had Rt.-ICA stenosis and 4 had Lt. ICA stenosis. Stenotic lesion existed beyond the level of the third cervical vertebral body in eleven cases, and so-called long segmental stenosis ranged from 3 to 5 cervical vertebral bodies in 3 cases. Before PTA, 14 patients underwent a balloon occlusion test for 3 to 20 minutes (average 9 minutes). Neurological symptoms of hemiparesis or sensory disturbance occurred in 3 patients during balloon inflation, but these disappeared completely after balloon deflation. It took from 1.5 to 2 hours (average 1.7 hours) to carry out PTA including the balloon occlusion test. All cases had satisfactory results with no morbidity or mortality. The mean stenosis ratio of pre-PTA, approximately 80% (55-93%), improved to that of 22% (0-50%) after PTA. Bradycardia and hypotension occurred transiently in 9 cases during and after PTA, but no symptoms remained by atropine sulfate and catecholamine infusion intravenously. In the following 1 to 26 months (mean 9.0 months) after PTA, 3 cases restenosed. The restenosis was recognized by MR angiography after 8 to 26 months (average 15.7 months) of PTA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877729 TI - Oxidative mechanisms involved in kainate-induced cytotoxicity in cortical neurons. AB - In our previous experiments, evidence of free radical formation has been demonstrated in gerbil brain after kainic acid (KA) administration. In the present study, the mechanisms involved in KA-induced free radical formation and subsequent cell degeneration were investigated using high density cortical neuron cultures. A free radical trapping agent, alpha-phenyl-N-tert- butyl-nitrone (PBN), as well as the combined action of superoxide dismutase and catalase attenuated KA neurotoxic effect. Calpain-induced xanthine oxidase (XO) activation may play an important role in KA excitotoxicity since calpain inhibitor I as well as allopurinol, a selective XO inhibitor, significantly protected the cortical neurons from KA-induced cell death. However, XO activation may not be the only source producing free radicals, other free radical generating systems such as nitric oxide synthase may also play a role in KA insult. PMID- 7877733 TI - [A clinical study of 21 patients with neurofibromatosis I and II]. AB - Neurofibromatosis (NF) 2, associated with bilateral acoustic neurinomas has been shown to be an entity distinct from NF 1, since their chromosomal abnormalities are completely different. NF 2 has a very low occurrence rate, but would be a terrible disease by its high prevalence of offsprings. In addition, compared to the majority of unilateral, nonfamiliar neurinoma, acoustic neurinomas of NF 2 have been shown to be refractory to treatments. Therefore, it is crucial to know the clinical characteristics of patients with NF 2. In this study, we analyzed 14 cases of NF 2 and 7 cases of NF 1 in whom brain tumors are main symptoms. Brain tumors associated with NF 1 were five neurinomas, two gliomas and a meningioma. The mean age of NF 1 patients accompanied with brain tumors was 37.6 years old, younger than the overall age of NF 1 patients. In patients with NF 2 there was often association with cranial, and spinal neurinomas and meningiomas. NF 2 especially, in younger patients was accompanied with multiple spinal neurinomas. Twenty acoustic neurinomas in 14 NF 2 patients were treated by surgery. Operative results showed that total resection was achieved in only 5 cases, 13 were subtotally and 2 were partially resected. Hearing preservation was attained in only three cases. In addition, all but two patients were complicated with postoperative facial palsy. From this analysis, it is clear that NF 2-associated acoustic neurinomas are not responsive to surgical intervention. We also reviewed genetical problems briefly. PMID- 7877734 TI - [Anterior transcallosal approach for the mass lesions in and around the third ventricle: with particular reference to the method of enlarging the foramen of Monro]. AB - Enlargement of the foramen of Monro is an essential maneuver to obtain an appropriate surgical view when large, solid lesions in and around the third ventricle are to be removed via the anterior transcallosal approach (ATA). For this purpose, three methods, i.e., the subchoroidal, transchororidal, and transfornicial approaches have so far been reported. However, since the locations and the pathological natures of space occupying lesions in this region are widely variable, the indication as well as the feasibility of each approach has remained rather unclear. The present paper deals with our surgical experience with six patients (2 gliomas, 1 angioma, 1 AVM, 1 plexus papilloma, 1 basilar top aneurysm) operated on using the ATA in which variable methods of enlarging the foramen of Monro were employed. Aiming at complete removal or clipping of the lesion, the seemingly best among the above three approaches was determined preoperatively, considering the size, location, and pathological nature of the lesion. The shape of the choroid plexus of the roof of the IIIrd ventricle as revealed by MRI was also taken into account. The subchoroidal, transchoroidal, and the transfornicial approaches were employed in 3, 2, and 1 cases, respectively. Except for one glioma which ended up being removed extensively, all the tumors and AVM were totally removed and the aneurysm successfully clipped. From the above experience, the merits and demerits of each approach for different types of lesions are discussed in view of their suitability for achieving total removal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877732 TI - [Treatment of intractable postherpetic neuralgia and blepharospasm: intraneural injection of adriamycin]. AB - Adriamycin, an anthracycline antineoplastic agent, can swiftly be transported to the sensory or somatic motor neurons by way of axoplasmic transport when injected into the subepineurium of the trigeminal nerve or sciatic nerve in experimental animals, and is consequently able to induce degeneration of the neurons without any systemic side effects. Intraneural injection of this agent was carried out for the treatment of a total of 22 patients presenting with intractable neural dysfunction (12 with neuralgia, including 7 with post-herpetic neuralgia and 10 with facial dystonia). The nerve which innervated the affected site was exposed under local anesthesia and approximately 10-60 microliters of 1-20% adriamycin was injected into the subepineurium. Results of the treatment after average follow-up periods of 21.5 months were as follows: Out of 12 patients with neuralgia, good results were obtained in 2 cases (16.7%), fair results in 6 cases (50.0%) (overall effective rate 67.7%). There were no changes in symptoms in 4 cases (33.3%). Out of 10 patients with facial dystonia, good results were obtained in 2 cases (20.0%), fair in 2 cases (20.0%) (overall effective rate 40.0%), and no changes in symptoms in 6 cases (60.0%). No major complications were encountered during these procedures and, once symptoms had disappeared after the treatment, no recurrence of symptoms was experienced. This method clearly differs from other various kinds of simple peripheral neurotomy, since transection of the peripheral nerve does not cause any, destructive changes in the sensory ganglion or motor nucleus and, hence, symptoms may recur.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877735 TI - [Intra-and extracranial chondrosarcoma]. AB - A 17-year-old female, who had diplopia and progressive gait disturbance, had been diagnosed as having a right parasellar mass lesion in 1986. Initial CT scan failed to show a parasellar space occupying lesion, although it was well demonstrated on MRI. No surgery was carried out at that time. Seven years later, she was hospitalized because of progressive gait disturbance, lower cranial nerves palsy, and cerebellar sign as well as the known right abducence palsy. At this time, CT scan exhibited a huge low density area with a marginal high density area suggesting calcification, which extended from the right parasellar area to the ventral portion of the midbrain. She underwent surgery under the diagnosis of cartilaginous tumor or chordoma. The intracranial lesion was removed via combined translabyrinthine approach and epidural subtemporal approach. The tumor was hitologically diagnosed as well-differentiated chondrosarcoma. Electron microscopy demonstrated tumor cells with features of chondrocytes. Since the original site of the tumor, strategies for treatment and prognosis are different from each other, distinction between chondrosarcoma and chordoma is important. MRI seemed very useful for making this distinction as a first step. PMID- 7877736 TI - [Brain stem glioma induced by radiotherapy: report of a case]. AB - A case of brain stem glioma following radiotherapy for brain tumor is presented. A 44-year-old female was admitted with chief complaints of gait disturbance and disturbed consciousness. She had received radiation therapy with 60Gy following resection of a right temporal astrocytoma 20 years before, but until admission this time follow up CT scan had shown no regrowth. On admission CT scan and MRI showed an enhanced mass (2 x 2.5cm) in the mid-brain. Tumor biopsy was performed using the subtemporal approach. The histological diagnosis showed a fibrillary astrocytoma grade III. The patient received postoperative synchronized chemotherapy but expired 8 months after admission. The growth of glioma appeared in the previous radiation field after a long latent period. This case should be considered not as a case of the regrowth of a tumor but as a case of a radiation induced tumor. Although 77 cases of gliomas following radiation for intracranial tumor have been reported, this case of radiation-induced brain stem glioma is extremely rare. PMID- 7877737 TI - [Successful treatment with administration of systemic high dose methotrexate and intraarterial carboplatin for osteosarcoma of the skull: a case report]. AB - An 11-year-old boy was admitted with a painless lump in the right frontal area as his chief complaint. On admission, physical and neurological examinations were normal except for the localized lump constituting the frontal lesion. Skull roentgenogram showed an osteoblastic and osteolytic mass with radiating bony spicules "sunray appearance" around the coronal suture. CT scans demonstrated it more clearly. The initial surgery was performed in July 1993. Pathological specimen showed osteosarcoma of the skull. The patient was transferred to our hospital for chemotherapy. The regimen consisted of intravenous high dose methotrexate 9,000 mg given for 6 hours with leucovorin rescue in a single course. Following 4 courses of high dose methotrexate, he underwent residual tumor resection. Two courses of intraarterial carboplatin 150 mg and methotrexate 200 mg were also given. Histologically, the lesion showed complete remission of the tumor, and no viable tumor cells were seen. Two additional courses of high dose methotrexate were given. The patient is doing well without evidence of recurrence. This case indicates that the chemotherapy with systemic high dose methotrexate and intraarterial carboplatin and methotrexate is effective for skull osteosarcoma. PMID- 7877738 TI - [Dural AVF of the posterior fossa associated with sinus occlusion presenting as intracerebral hemorrhage: case report]. AB - A 69-year-old man was admitted because of sudden onset of consciousness disturbance. Neurological examination on admission revealed slightly disturbed consciousness, sensory aphasia and right hemiparesis. CT scan disclosed a hematoma in the left posterior temporal lobe. Left carotid angiograms showed dural AVF of the transverse/sigmoid sinus fed mainly by the left occipital and posterior auricular arteries. On the angiograms the left sigmoid sinus was completely occluded. This was associated with retrograde venous flow into the cortical veins, the superior petrosal sinus and the contralateral traverse sinus. After stabilizing the condition, we totally resected the dural AVF including the left transverse sinus. The postoperative course was uneventful. Histopathological examination of the surgically resected specimen revealed that the dural A-V fistula per se existed in the sinus wall. PMID- 7877739 TI - [Pharmacokinetics of intratumoral interferon-gamma activity following subcutaneous administration of recombinant interferon-gamma in a patient with metastatic brain tumor derived from renal cancer]. AB - Pharmacokinetic studies of intratumoral interferon (IFN)-gamma activity were performed 1 week and 1 month after subcutaneous (s.c.) administration of recombinant IFN-gamma (specific activity = 1 x 10(7) units/mg protein) to a patient with metastatic brain tumor in the right occipital lobe derived from primary renal cancer. The patient, a 54-year-old man, underwent total removal of the lesion on April 10, 1991, with placement of an indwelling Ommaya Reservoir in the tumor cavity. The histological diagnosis was clear-cell carcinoma. His postoperative course was uneventful. Due to detection of a new ring-like enhancing mass in the right temporal lobe on serial CT examination on May 27, radiotherapy was discontinued immediately after delivery of a total dose of 30 Gy. Recombinant IFN-gamma was then administered s.c. at a dose of 3 x 10(6) units/day for 6 weeks, and induced a partial response. During IFN-gamma therapy, IFN-gamma activity in intratumoral fluid was measured 0 min, 30 min, 90 min and 6 hours after s.c. injection of IFN-gamma. The level of IFN activity was determined by an enzyme-linked immunosorbent assay. Intra-tumoral IFN-gamma activity gradually increased, and showed the highest of measured values at 6 hours after administration, while serum IFN activity decreased rapidly with a half-life of 30 min. The patient was discharged on July 30, but died from complications of aspiration pneumonia on September 2, 1991. PMID- 7877740 TI - [Orbital varix presenting orbital apex syndrome]. AB - On 7 July 1993, a 61 year-old female presented a seven-day history of double vision and retro-ocular pain. Neurological examination on admission demonstrated right oculomotor palsy and pain in the right frontal nerve. Routine CT scan and MRI disclosed no abnormalities. Her symptoms deteriorated progressively and increased in severity, resulting in complete ptosis and visual disturbance in the right eye, for which she was hospitalized. Angiography also failed to demonstrate any lesion. Herrical CT scan demonstrated a small mass lesion at the right orbital apex. A frontotemporal extradural approach operation was performed on July 6, 1993. The anterior clinoid process and minor wing of the sphenoid were drilled to expose the optic canal and the superior orbital fissure. When the periorbita just beside the optic sheath was opened, a large vein was observed to be impinging on the optic nerve and nerves which pass through the superior orbital fissure. This vein was carefully dissected, coagulated and removed. The postoperative course was uneventful. Her severe retro-ocular pain completely disappeared immediately after the operation. Although complete remission of ptosis and return of eye movements to normal were noted, her visual acuity is at present limited to hand movement. Orbital varix is a common cause of unilateral intermittent proptosis. However, there has been no report in the literature of orbital varix with orbital apex syndrome as the initial clinical appearance. In this type of patient with orbital varix and retrobulbar hemorrhage or impairment of intraorbital nerves, surgical intervention using a transcranial approach to the lesion should be undertaken. PMID- 7877741 TI - [Improvements and problems in the new WHO classification of brain tumors]. PMID- 7877742 TI - The effects of sex steroids, and the X chromosome, on female brain function: a study of the neuropsychology of adult Turner syndrome. AB - Sex steroids and the X chromosome can independently affect cognitive abilities. Because subjects with Turner syndrome (TS) have gonadal aplasia, and various alterations in X chromosome structure and number, they provide a model to study the effects of sex steroids and of the X chromosome on human brain function. We used neuropsychological tests to study the cognitive abilities of 18 TS adults and 19 age/sex matched healthy controls. Nine TS subjects were mosaic for the 45,X karyotype, and 9 were non-mosaic 45,X (full TS). The TS group as a whole, compared to controls, had (i) significantly lower scores in tests of language and visual-spatial function, attention and memory, and (ii) a significantly greater discrepancy between verbal and performance scores. Mosaic TS subjects were intermediate between full TS and controls in some tests of verbal ability, but did not differ significantly from controls in others. Visuospatial ability was significantly lower than controls in both mosaic and full TS. Within the mosaic TS group, there was a significant negative correlation between visuospatial ability and % lymphocytes having a 45,X karyotype. Memory test scores were reduced independently of "X chromosome dosage" in all TS subjects. We conclude that in humans, the X chromosome is involved in development of both cerebral hemispheres, but moreso of the association neocortices. Also, sex steroids may modulate this effect--particularly in hippocampus. PMID- 7877743 TI - Hemispheric differences in global and local processing dependent on exposure duration. AB - The main purpose of the present experiment was to examine hemispheric differences in the analysis of global and local components of verbal hierarchical stimuli, by manipulating the parameters of the procedure, in the form of varying duration exposures (50, 100 and 200 msec). Subjects had to decide whether or not a target letter appeared in the stimuli. The results provide evidence that the cerebral hemispheres may differ in their ability to process global and local information, but only under certain conditions. A RH-LVF advantage in accuracy rate was found in the detection of the target at global level and a LH-RVF advantage in the detection of the target at local level, but only with a presentation of 50 msec. At 100 and 200 msec of exposure duration, differences between the two hemispheres were not found. PMID- 7877744 TI - Axis-based neglect of visual shapes. AB - A new test of "object-centered" visual neglect uses equilateral triangles, with ambiguous principal axes that can be manipulated by context. Three left neglect patients detected gaps in such triangles. The location of the gap relative to the biased principal axis was varied, while maintaining the same egocentric locus. More gaps were missed on the left of the axis. This supports Driver and Halligan's (Cognit. Neuropsychol. 8, 475-496, 1991) claim that neglect can apply to the contralesional side of a shape's principal axis, while avoiding serious flaws in their method. The relation between axis-based neglect and other cases of object-centred neglect is discussed. PMID- 7877746 TI - Parkinsonian patients without dementia or depression do not suffer from bradyphrenia as indexed by performance in mental rotation tasks with and without advance information. AB - A predominant symptom of Parkinson's disease is akinesia and bradykinesia, slowing in the initiation and execution of voluntary movement. There has long been speculation as to whether cognitive processes undergo similar processes, but findings may be confounded by the frequent co-occurrence of dementia and/or depression. Mental rotation provides an internal or cognitive analogue of real movement, and enables us to determine the speed of such mental processes independent of any concurrent motor slowing in response initiation and execution. Medicated patients with Parkinson's disease who were free of dementia and depression were found to be able to mentally rotate alphanumeric or figural stimuli, with and without advance information as to the view (front or back) of a stick figure shortly to be shown, as rapidly as normal healthy controls. We conclude that cognitive processes involved in mental rotation are not necessarily slowed in Parkinson's disease. PMID- 7877745 TI - Parkinson's disease: reorganization of the reach to grasp movement in response to perturbation of the distal motor patterning. AB - This study assessed the kinematic changes to the reach to grasp movement in response to a perturbation of object size in 15 Parkinson's disease (PD) and 15 control subjects. For non-perturbed trials subjects reached 35 cm to grasp and lift either an illuminated small (0.7 cm) or large (8 cm) diameter cylinder. For perturbed trials (20%), illumination shifted unexpectedly from the small to the large or from the large to the small cylinder at the onset of the reach. For Condition One trials subjects were given no instructions as to which grasp to use. With perturbation, they thus naturally changed grasp from precision grip to whole hand prehension or vice versa. The results for the PD subjects indicated a slowness at the transition from one to another grasp. This contrasted to the smooth transitions when perturbation required only a change of grasp aperture (precision grip--Condition Two; whole hand prehension--Condition Three). PD subjects thus showed dysfunction in the suppression/activation of different grasp programs rather than deficits in the on-line modification of an operating program. PMID- 7877748 TI - The stability of tachistoscopic measures of hemispheric specialization. AB - Two-week test-retest reliabilities were determined for two tachistoscopic tasks, consonant-vowel-consonant trigrams and dot location, in 48 right-handed university students. Both visual field and laterality scores were examined. Analysis of variance showed no significant main effects or interactions of session for either task, indicating stability of mean performance and laterality scores. Likewise, grouping subjects as "high" or "low" by median laterality scores showed concordance across sessions for both tasks. Test-retest correlations were moderately high for all verbal task measures and for visual field scores for the dot location test. However, laterality indices for dot location showed low stability despite comparable within-session reliabilities of laterality scores for the two tasks. These findings suggest stability of group means and subgroups for verbal and dot location tachistoscopic measures. However, the degree to which individual scores are predictable from one session to the next differs between the two tasks. PMID- 7877747 TI - Asymmetric performances in binaural localization of sound in space. AB - Twenty right-handers and 20 left-handers were tested on a sound localization task. Broadband noise was presented from either the left or right hemifield. Localization accuracy was significantly greater (P = 0.002) when sounds emanated from the left hemifield thereby suggesting a paramount role played by the right hemisphere. Correcting for front-rear reversals, attributable to impoverished spectral cues and/or faulty processing of such cues, rendered differences in error scores linked to hemifield nonsignificant. The data were interpreted to mean that the special contribution of the right hemisphere to this task was its greater fidelity in processing spectral cues. No differences in localization proficiency between right- and left-handers were observed. PMID- 7877749 TI - Challenging current accounts of unilateral neglect. AB - Two left-neglect patients were asked (i) to bisect a 15 cm line, (ii) to bisect the empty space between the endpoints of a 15 cm virtual line, and (iii) to set the endpoints of a 15 cm virtual line, given its midpoint. With one patient, the subjective midpoint of the virtual line was found to be displaced leftwards with respect to the subjective midpoint of the real line, whereas with the other it was found to be displaced rightwards. However, in condition (iii) both patients significantly underestimated the distance from the centre of the rightmost point of the virtual line while relatively overestimating that from the centre to the left endpoint. This latter result challenges current accounts of unilateral neglect. PMID- 7877750 TI - Production of short timing responses: a comparative study with a deafferented patient. AB - How far can proprioception contribute to time keeping? To answer this question, a deafferented patient and neurologically normal subjects produced 1- or 5-sec durations in a sustained (continuous finger press) or discrete (two successive finger taps) manner, with and without Knowledge of Results. The findings were that: (1) proprioceptive afferents contribute to timing regulation in motor production of short durations; (2) this role can be rapidly compensated by Knowledge of Results; (3) the proprioceptive contribution is more important for sustained than for discrete performances; (4) stable performances are produced even when KR is withdrawn, suggesting familiarization with KR leads to the establishment of a mnemonic trace. PMID- 7877751 TI - Effects of serotonin receptor blockade by methysergide on loaded breathing in the rabbit. AB - Previous works demonstrated that the excitatory role of serotonin (5 hydroxytryptamine, 5-HT) on ventilation is mediated by 5-HT1,2 receptors stimulation. We hypothesized that load-induced hypoventilation could be minimized by a central release of 5-HT. Conversely, blockade of 5-HT receptors should accentuate hypoventilation. We compared the ventilatory effects of methysergide (MS), a 5-HT1,2 receptors antagonist, in 3 groups of anesthetized, spontaneously breathing rabbits: (1) a group of animals breathing for 60 min through a 370 cm H2O.liter-1.s inspiratory resistive load (IRL group), whose paCO2 increased with IRL; (2) a Control group; (3) a Control + CO2 group, made hypercapnic to assess the possible effect of this stimulus on the ventilatory responses to MS. In the 3 groups, i.v. injection of MS induced the same ventilatory changes, characterized by a rapid shallow breathing with a shorter integrated diaphragmatic activity. This confirms the tonic facilitatory effect of 5-HT on ventilation and suggests that IRL would not increase 5-HT release in the sites close to the respiratory nuclei. PMID- 7877752 TI - Proliferative astrocytes may express fibronectin-like protein in the hippocampus of epileptic rats. AB - Kainic acid treatment, a model of temporal lobe epilepsy, induces in CA3-CA4 fields of hippocampal complex a neuronal degeneration associated with glial hypertrophy and proliferation. After treatment with kainate, fibronectin (an extracellular matrix protein) immunoreactivity increases in CA3-CA4. Fibronectin antibodies stain proliferative cells (simultaneously labelled by [3H]thymidin) of astrocytic type (double-immunostained by GFAP antibodies). This result constitutes the first direct demonstration of astroglial fibronectin expression in vivo. In the molecular layer of kainate-treated rats there is an axon-terminal degeneration of association-fibers. This is associated with a transient hypertrophy of resident astrocytes but not with any glial proliferation. Reactive astrocytes do not express (or faintly) fibronectin immunoreactivity in this layer. Since fibronectin is involved in astroglial proliferation in vitro, the present observations suggest that astrocytes contribute in vivo to the astroglial proliferation by an autocrin mechanism. PMID- 7877753 TI - Examination of the natural protein substrates affected by staurosporine in the developing cerebral cortex. AB - The protein substrates affected by staurosporine (SP), the most potent inhibitor of protein kinases yet described, are unknown. In order to approach this problem we incubated cerebral cortex tissue with 0, 20, 50 and 100 nM of SP using [32P]orthophosphate as radioactive precursor. The analysis of the phosphoproteins were made with a modified high resolution two dimensional gel electrophoresis, followed by autoradiography. We detected several proteins affected by SP. Specially noticeable was an approximately 55 kDa protein which strikingly diminished the intensity of phosphorylation. However, the reverse phenomenon was also observed. To the best of our knowledge this is the first examination of protein substrates affected by SP in intact tissue. PMID- 7877754 TI - Ubiquitinated dystrophic neurites suggest corticospinal derangement in patients with amyotrophic lateral sclerosis. AB - Pathologic changes affecting the upper motoneuron (UMN) were studied in 37 cases of amyotrophic lateral sclerosis (ALS) by histology and immunohistochemistry and by electron and immunoelectron microscopy. The most striking finding was represented by ubiquitin-positive dot-like structures related to (1) glial lipofuscin granules, (2) small polyglucosan bodies and (3) dystrophic neurites. Their distribution areas did not overlap. In ALS cases, ubiquitinated dystrophic neurites were twice as frequent as in controls in the arcuate region of motor cortex; moreover, in ALS cases they were twice as frequent in the spinal cord at the end of corticospinal tracts, compared with the motor cortex. These findings may indicate the presence in ALS of a 'dying-back' of the corticospinal motoneuron, independently of its primary or secondary involvement. PMID- 7877755 TI - Choline acetyltransferase activity is reduced in rat nucleus accumbens after unlimited access to self-administration of cocaine. AB - Choline acetyltransferase (ChAT) activity was measured in discrete areas of rat brain after chronic, unlimited access to self-administration of cocaine. Mean activity of ChAT was reduced by approximately 30% in the nucleus accumbens, both on the last day of cocaine access and after 3 weeks cocaine withdrawal. These data suggest that chronic cocaine exposure might inhibit nucleus accumbens cholinergic neurones which could underlie some of the behavioral effects of cocaine. PMID- 7877756 TI - Effect of [dl]-alpha-tocopherol on FeCl2-induced lipid peroxidation in rat amygdala. AB - Peroxidative injury of neural membrane lipids can be initiated by iron-containing blood products, chelated ferrous or ferric ions, and low valence iron in aqueous solution. Lipid peroxidation was measured following focal injection of 3 microliters of 100 mM FeCl2 into rat amygdala. Acute parenteral administration of [dl]-alpha-tocopherol as the alcohol limited the quantity of peroxidation products generated. These data suggest a potential role for alpha-tocopherol administration in limiting brain injury responses. PMID- 7877757 TI - Spared descending pathways mediate locomotor recovery after subtotal spinal cord injury. AB - The location of pathways responsible for locomotor recovery after incomplete spinal cord injury has been studied in adult rats. Animals were allowed to recover from subtotal mid-thoracic cord section which spared left lateral and ventral funiculus fibers. Subsequent lumbar commissurotomy or left thoracic cord hemisection abolished the locomotor recovery. Spared descending fibers passing through the initial incomplete cord lesion appear to mediate locomotor recovery. PMID- 7877758 TI - The silent period after transcranial magnetic stimulation is of exclusive cortical origin: evidence from isolated cortical ischemic lesions in man. AB - In two representative patients suffering from focal isolated ischemic lesions of the arm-associated (patient 1) or leg-associated (patient 2) primary motor cortex excitatory responses (motor evoked potentials, MEPs) and inhibitory phenomena (silent period, SP) following transcranial magnetic motor cortex stimulation (TMS) are demonstrated. Furthermore, supramaximal peripheral nerve stimulations for testing spinal inhibitory actions were performed. Results were compared to a control group of 12 normal subjects. In patient 1, SP induced by TMS in the clinically affected left extensor carpi radialis muscle (ECR) was lacking in the presence of an only marginally reduced MEP and a normal spinal silent period in this muscle. Normal MEPs and SP durations were observed in the right ECR and in the first dorsal interosseus (FDI) and anterior tibial (TA) muscles on both sides. Similarly, in patient 2 a loss of SP induced by TMS in the clinically affected right TA was observed with normal SP durations in the left TA and both FDI muscles and normal MEP amplitudes in all muscles studied. It is concluded that both early and late phases of SP induced by TMS are of cortical origin and generated in the primary motor cortex. PMID- 7877759 TI - A population of cells in the human thalamic principal sensory nucleus respond to painful mechanical stimuli. AB - A population of neurons located in the cutaneous core of the principal sensory nucleus of human thalamus (ventralis caudalis, Vc) has been identified that had their maximal response to mechanical stimuli which were perceived as painful by the patients involved. None of these cells responded to painful thermal stimuli. The graded responses of these cells to mechanical stimuli extending into the painful range suggest they both mediate acute pain in response to mechanical stimuli and participate in mechanical hyperalgesia. PMID- 7877760 TI - Hemeoxygenase expression after reversible ischemia of rat brain. AB - Heme oxygenase (HO-1) gene expression was studied in the brains of rats subjected to 30 min global cerebral ischemia followed by recirculation of up to 24 h. Total RNA was isolated from the cerebral cortex, striatum and hippocampus and reverse transcribed into cDNA. cDNA was taken as template for PCR using HO-1-specific primers. We found that, when PCR reactions were run for 22 cycles, the amount of PCR products correlated closely with the amount of cDNA. HO-1 gene expression was sharply increased after cerebral ischemia in all three brain structures studied. In the cortex and striatum, the HO-1 mRNA content increased constantly after cerebral ischemia up to 24 h of recovery, being 8- and 9-fold over control after 24 h of recirculation in the cortex and striatum, respectively. In the hippocampus, HO-1 mRNA levels peaked at 4 h after ischemia (9-fold over control) and declined thereafter to 4.5-fold over control 24 h after ischemia. Assuming that the observed increase in mRNA levels is paralled by increased HO-1 protein synthesis, formation of the products of HO reaction, biliverdin and carbon monoxide, is activated after ischemia. These products may produce different and divergent effects on the recovery from the metabolic stress produced by cerebral ischemia. PMID- 7877761 TI - Accumbens microinjection of LY 171555 and sulpiride: effects on circling behaviour, in the rat. AB - In rats with unilateral 6-hydroxydopamine lesions of the substantia nigra (pars compacta) and amphetamine i.p. some parameters of the rotational activity, following intra-accumbens microinjection of D2 agonist (LY 171555) and antagonist (sulpiride), have been analyzed. An increase in the number of turns was observed with LY 171555, whereas sulpiride determined a decrease. The type of circling was also analyzed: D2 agonist induced a very close turn around the central axis of the animal and D2 antagonist a close turn in the centre of the cage. Data were compared with control condition, which exhibited a large turn around the walls of the cage. The results show that pharmacological manipulation of nucleus accumbens influences rotational behaviour with a specific role for D2 receptors. PMID- 7877762 TI - Effects of neuroactive compounds, noxious and cardiovascular stimuli on the release of amino acids in the rat locus coeruleus. AB - The release of excitatory amino acids (glutamate, aspartate), inhibitory amino acids (GABA, taurine) and arginine was determined in the locus coeruleus (LC) of anaesthetized rats. The neuronal origin of stimulated amino acid release was verified by superfusion with neuroactive compounds. Electrical stimulation of the sciatic nerve, as well as mechanical footshock, enhanced LC release rates of glutamate and aspartate without influencing those of taurine and arginine. GABA release rate was increased slightly after some delay. Excitatory amino acid release was not influenced by changes in blood pressure. The results provide direct neurochemical evidence that noxious stimuli activate LC neurons via the glutamate and aspartate input into this nucleus. PMID- 7877763 TI - Impairment of place navigation of rats in the Morris water maze by intermittent light is inversely related to the duration of the flash. AB - The relative contribution of allocentric and egocentric orientation to place navigation was studied in Long-Evans rats trained in the Morris water maze in permanent light, permanent darkness or flickering light (1 Hz, flash durations 25, 100, 300, 500 and 800 ms). After 3 days of training (nine blocks of four trials), escape latencies were 38 and 7 s in the dark- and light-trained groups, respectively, and corresponded to the light-dark ratio in the flicker-trained groups. Shorter-than-predicted latencies in the 25- and 100-ms groups reflected visual persistence of approximately 200 ms. The difference between flickering light (100 ms) and permanent light performance during acquisition of place navigation to a new target was significantly smaller in rats previously trained in light than in naive animals. It is concluded that longer flash duration gives the animals more opportunities to locate relevant landmarks and to estimate their distance. PMID- 7877764 TI - Presynaptic alpha 2-adrenoceptors inhibit calcium influx in terminals of chicken sympathetic neurons and noradrenaline release evoked by nicotinic stimulation. AB - The changes of intracellular calcium concentration evoked by stimulation of nicotinic receptors and its modulation by alpha 2-adrenoceptors were investigated in chicken sympathetic neurons grown in culture. Stimulation of nicotinic receptors increased the intracellular calcium both in the area of cell bodies and processes. In normal extracellular calcium (1.3 mmol/l), the specific alpha 2 adrenoreceptor agonist UK 14,304 (10 mumol/l) diminished the response in cell bodies but not in processes. The same treatment in medium with reduced calcium (0.13 mmol/l) resulted in the decrease of the response evoked by nicotinic stimulation in the area of processes but not in the cell bodies. The effect of UK 14,304 on evoked noradrenaline release paralleled its influence on intracellular calcium in processes. These data indicate that nicotine stimulation-induced influx of calcium is inhibited by alpha 2-adrenoceptor stimulation both in cell bodies and in processes. It is concluded that the nicotinic stimulation-evoked release of noradrenaline is triggered by influx of calcium through alpha 2 adrenoreceptor sensitive as well as insensitive pathways. PMID- 7877765 TI - Astrocytes but not microglia express NADPH-diaphorase activity after motor neuron injury in the rat. AB - The purpose of this study was to identify cellular sources of nitric oxide (NO) after injury to rat facial motor neurons using NADPH-diaphorase histochemistry. We employed intraneural injections of either saline or toxic ricin, followed by nerve crush, in order to produce regeneration or degeneration of facial motor neurons (FMNs), respectively. Reactive astrocytes responding to ricin-induced degeneration of FMNs showed increased NADPH-diaphorase activity while reactive astrocytes responding to axotomy (saline injection) did not. Reactive microglial cells were found not to express NADPH-diaphorase in either one of these two paradigms. We conclude that irreversible neuron injury resulting in neurodegeneration causes increased production of NO by reactive astrocytes. PMID- 7877766 TI - Noxious distention of viscera results in differential c-Fos expression in second order sensory neurons receiving 'sympathetic' or 'parasympathetic' input. AB - Visceral organs receive dual innervation from primary afferents commonly referred to as 'sympathetic' and 'parasympathetic' afferents. We have previously reported a significantly greater induction of immediate-early genes in the viscerotopically appropriate spinal cord segments receiving 'parasympathetic' afferent innervation (pelvic nerve) compared with those receiving 'sympathetic' afferent innervation (hypogastric nerve) following noxious colorectal distention. In this study, the nucleus of the solitary tract (NTS) and viscerotopically appropriate spinal cord segments were labeled immunocytochemically for c-Fos following noxious gastric or esophageal distention to determine if the differential labeling following 'sympathetic' (spinal) and 'parasympathetic' (vagal) visceral afferent input is a general phenomenon of the gastrointestinal tract. Gastric distention and esophageal distention induced considerable c-Fos in the NTS and virtually none in the thoracic spinal segments. These data suggest that 'parasympathetic' visceral afferents may be different than 'sympathetic' visceral afferents with respect to their ability to induce c-Fos following noxious visceral distention. PMID- 7877767 TI - REM-sleep propensity accumulates during 2-h REM-sleep deprivation in the rest period in rats. AB - Two-hour, highly-selective, rest-period, rapid-eye-movement (REM)-sleep deprivation (RD) was performed on rats to characterize the time-course of the homeostatic response to REM-sleep loss. RD caused a dramatic and progressive increase in the frequency of attempts to enter REM sleep, suppressed non-REM sleep EEG delta power, and (in late rest period trials) was followed by a rebound increase in REM-sleep expression. PMID- 7877769 TI - Scholarship: three essential processes. PMID- 7877768 TI - Ethanol augments pre-emptive analgesia produced by nitrous oxide in the formalin test in the rat. AB - Experimental evidence suggests that the introduction of analgesia prior to a painful stimulus can reduce the subsequent pain (preemptive analgesia). Using the formalin test model, previous studies have demonstrated that general volatile anesthetics reduce the pre-emptive analgesia produced by nitrous oxide administration in the rat. The present study compared the influence of halothane and ethanol on the response to formalin injection in rats previously exposed or not exposed to nitrous oxide. Nitrous oxide decreased second phase licking behavior by approximately 70% from controls. Halothane decreased second phase licking by 37% from sham animals and, when administered with nitrous oxide, mitigated the suppression of licking seen with nitrous oxide alone. Ethanol reduced the licking response in both early and late phases following formalin injection. In contrast to halothane, ethanol failed to attenuate the analgesia produced by nitrous oxide administration alone. Thus, ethanol provides apparent analgesia following formalin injection and, unlike halothane, augments the preemptive analgesia produced by nitrous oxide. PMID- 7877771 TI - Knowledge of nursing faculties. PMID- 7877770 TI - Nursing theory-guided practice: what it is and what it is not. PMID- 7877772 TI - The threat of verbal technologies. PMID- 7877773 TI - Theory for nursing practice. AB - This article chronicles the development of nursing theory and research over the past 30 years as it parallels the author's own development as a theorist researcher. Dorothy Johnson and Martha Rogers are considered the contemporary forerunners of a shift from an emphasis on medical knowledge to an emphasis on distinctly nursing knowledge. The paradigm shift Rogers called for was largely misunderstood at the time of its inception, resulting in attempts to force holistic thinking into reductionistic methods of research. The epistemology of nursing research lagged behind the ontology of the discipline. Moreover, the absence of an agreed-upon focus of the discipline created a void in the development of theory specific to nursing practice. The author asserts that the focus and paradigm of the discipline of nursing are now clear. The core, purpose, and societal commitment of nursing as a practice discipline are captured in the phrase, caring in the human health experience. Research methods that reflect a unitary, transformative paradigm make it possible to develop theory that structures practice. PMID- 7877774 TI - Aesthetic knowing grounded in an explicit conception of nursing. AB - This article presents an expanded perspective of aesthetic knowing in nursing grounded in the theory of nursing as caring. The authors highlight Carper's contributions to nursing, applauding the value of her work. However, a major limitation of Carper's work on aesthetic knowing is the failure to provide an explicit conception of nursing to guide the search for patterns and structure of nursing knowledge, thus the limited development of the aesthetic pattern of knowing in nursing. The authors propose that aesthetic knowing in nursing is the creating experience in the nursing situation, expression of the experience, and appreciation of it through encounter. PMID- 7877775 TI - No place of their own: an exploratory study. AB - The purpose of the research reported here was to explore with mothers and children the experience of having no place of their own. The researcher used Parse's theory of human becoming as a framework in this exploratory descriptive study. For the participants in this study the experience of living without a place of their own is: a sense of gratitude for protection, mingling with the discomfort of restriction and exposure, giving rise to fears and reassurances as detachment from cherished others surfaces discordance with unfamiliar patterns, while novel engagements bring pleasure as insights and struggles surface new possibles as well as disillusionment. Suggestions for theory expansion and further research are discussed. PMID- 7877777 TI - Hospital payment source and length-of-stay. AB - The primary aim of the research reported here is to examine elements of the theory of social organizations as adaptive systems as derived from Roy's model by investigating the ability of hospital payment source to predict length-of-stay. A retrospective review was conducted of 3,297 records of patients discharged under 1 of 10 frequently occurring diagnosis-related-groups. Two groups were formed to isolate the contextual stimuli-patients whose hospital care was paid for under a diagnosis-related-group payment system and patients whose hospital care was paid for under a per diem payment system. The Tilton 0 statistic indicated a high degree of similarity between the two patient groups. Thus, length-of-stay could not be effectively predicted based on the source of payment to the hospital. PMID- 7877778 TI - Radical health-care reform: the person as case manager. PMID- 7877776 TI - King's theory of goal attainment as a framework for managed care implementation in a hospital setting. AB - Implementation of nursing conceptual frameworks and theories in practice settings is essential to foster the growth and advancement of the discipline of nursing. Over the past several decades nurse educators, administrators, and clinicians have often seemed to function in isolation. Educators developed conceptual models and theories, but these frameworks were infrequently applied in practice settings. In addition, administrators used management theories as a framework for nursing practice in institutional settings, while clinicians were left to utilize the medical model and theories from other disciplines as a base to guide practice. This article focuses on how King's theory of goal attainment can serve as a nursing framework for managed care. PMID- 7877779 TI - The lived experience of staying healthy in rural African American families. AB - Decreased government spending for public health programs and increased government expectations that consumers should take responsibility for self-care and health promotion activities are current trends (Lee & Estes, 1990; Naisbitt, 1984). The purpose of this study was to reveal through phenomenological analysis the meaning of staying healthy for the participants. Staying healthy emerged as a dynamic response to life events that involved activity and relatedness in synchrony with life's rules and emotional tranquility. The findings confirm that phenomenological research can reveal the meaning of health within the context of culture and support the conceptualization of health as a developmental process for African American families. PMID- 7877780 TI - The core of advanced practice nursing. PMID- 7877781 TI - A Rogerian process of inquiry. AB - This article present a Rogerian process of inquiry that is proposed to be a creative and original method commensurate with the epistemological and ontological foundations of the science of unitary human beings and which supports the aim of Rogerian research to understand the nature of human evolution and its multiple, unpredictable potentialities. The development of this research methodology has been guided by Lincoln and Guba's (1985) paradigmatic approach to the identification of original processes of inquiry. PMID- 7877783 TI - Nursing theory-based research for advanced nursing practice. PMID- 7877782 TI - Nursing and the next millennium. AB - On March 19, 1993, in Toronto, Canada, at Discovery International, Inc.'s, Biennnial Nurse Theorist Conference, five theorists participated in a panel discussion on: caring as an essence of nursing; the value of continuing to develop nursing theory; what constitutes nursing research; the role of advanced practice nurses. The theorists were Imogene M. King, Madeleine M. Leininger, Rosemarie Rizzo Parse, Hildegard E. Peplau, and Martha E. Rogers. Marlaine C. Smith was the moderator and presented the questions to the panel. PMID- 7877784 TI - Charley potatoes or mashed potatoes? PMID- 7877785 TI - Charley potatoes or mashed potatoes? PMID- 7877786 TI - Nursing science as a basis for advanced practice. PMID- 7877787 TI - The meaning of retirement for communally-living retired performing artists. AB - The purpose of this qualitative descriptive transcultural study was to explore the meaning of retirement for those older people who have lived as performing artists and who are presently sharing communal living at the Casa Verdi di Riposo, Milan, Italy. Parse's nursing theory was the conceptual framework utilized to structure objectives and interview questions. Findings showed that the meaning of retirement for these communally-living retired performing artists is the emerging of an unburdening lightness as esthetic interconnections surface the was and will-be in the now moment as the diversity of everydayness enlivens through communion-solitude while anticipating the transposing vistas of the inevitable prompts treasuring the now in confirming a perpetual artistic legacy. Findings were congruent with Parse's three major themes (meaning, rhythmicity, and transcendence) and support Parse's theory of human becoming, as well as expanding the body of nursing knowledge on the phenomenon of retirement. PMID- 7877788 TI - Maternal cardiovascular hemodynamic adaptation to pregnancy. AB - Maternal cardiovascular adaptation to pregnancy involves enormous changes. Cardiac output increases in early pregnancy, initially as a result of an increased heart rate, soon followed by an increased stroke volume. Cardiac output continues to increase until midpregnancy, and remains stable afterward, with a possible small decline in the last weeks of pregnancy. Blood pressure decreases in early pregnancy, reaching a minimum in midpregnancy, then returning to baseline levels at term. Consequently, peripheral vascular resistance is reduced throughout pregnancy. Myocardial contractility seems to be increased during all trimesters of pregnancy, thus gradually provoking the development of a mild ventricular hypertrophy. The increase in preload, which develops in concert with the increment in blood volume, leads to an increase in left atrial diameter, which also begins during early pregnancy. During labor, both cardiac output and blood pressure increase. After delivery, cardiac output initially increases, but begins to decrease within the first hour to reach baseline levels 2 weeks postpartum. Most cardiovascular parameters show their greatest changes within 2 weeks postpartum. Five months postnatally, only a mild residual ventricular hypertrophy persists. PMID- 7877789 TI - U.S. Supreme Court decision: six months later. PMID- 7877790 TI - Congestive heart failure: dealing with the number one DRG (continuing education research). PMID- 7877791 TI - Effective inservice education process. PMID- 7877792 TI - Are you a supervisor? PMID- 7877793 TI - Adult day care: long term care "family style". PMID- 7877794 TI - Carefronting: caring enough to confront. PMID- 7877795 TI - No immunoglobulins in cataractous lenses. AB - All 47 human senile cataractous lenses studied by a direct immunohistochemical method for the presence of immunoglobulins yielded negative results. Consequently, cataract cannot be an autoimmune disease as has been suggested by some authors. PMID- 7877796 TI - Phospholipid analysis of mammalian optic nerve tissue: a 31P nuclear magnetic resonance spectroscopic study. AB - Phospholipids of optic nerve (n = 30) from 5.6-kg rabbits were analyzed by 31P nuclear magnetic resonance (NMR) spectroscopy. Phospholipid metabolites detected were as follows (mol %): phosphatidylcholine (PC; 25.82 +/- 0.12), PC plasmalogen/alkylacyl PC (2.07 +/- 0.13), sphingosylphosphorycholine (1.12 +/- 0.20), phosphatidylinositol (PI; 2.17 +/- 0.21), lyso PC (0.85 +/- 0.06), sphingomyelin (12.52 +/- 0.10); phosphatidylserine (PS; 14.38 +/- 0.11), phosphatidylethanolamine (8.98 +/- 0.11), ethanolamine plasmalogen (28.99 +/- 0.30), unidentified phospholipid (1.10 +/- 0.01), phosphatidic acid (PA; 1.72 +/- 0.06), and lyso PS (0.28 +/- 0.10). The bulk of the ethanolamine phosphatide is in the form of its plasmalogen, which is the major phospholipid detected. The choline plasmalogen, or a reduced derivative thereof, also is present; thus, a significant phospholipid biosynthetic pathway for optic nerve tissue involves the plasmalogen route, which is a pathway distinct from the PA route responsible for the synthesis of PS, PI, and PC. This new 31P NMR lipid analytical technique offers potential for studying optic nerve phospholipid metabolism and degenerating optic nerve tissue, since the technique can accurately quantitate (1) both plasmalogen and nonplasmalogen phospholipids, (2) minor phospholipid components, and (3) previously undetected phospholipids. PMID- 7877797 TI - Characterization of glycoconjugates in the human cameral mucous gel by lectins. AB - A cameral mucous gel (CMG) has been described in human eyes lining the anterior and posterior ocular chambers. We assay a battery of 11 lectins to characterize the accessible sugars of the presumed glycoproteins and glycosaminoglycans present in the gel. Results show a predominance of alpha-linked sugars over beta linked ones. There is evidence for the prominence in the gel of alpha-N-acetyl-D galactosamine and/or alpha-D-galactose, together with alpha-N-acetyl-glucosamine. The second most important sugars are beta-N-acetyl-D-glucosamine and the dissacharide beta-D-galactose-N-acetyl-D-galactosamine. beta-N-acetyl galactosamine could possibly be identified in third place. Neither fucose nor mannose are detected. These results point towards heparan and perlecan as possible components of the glycidic fraction of the gel, although a specific proteoglycan adapted to the osmotic role of the CMG is not at all unlikely. PMID- 7877798 TI - The epithelial barrier function in clear corneal grafts. AB - We conducted a corneal epithelial permeability study using a fluorophotometer on 93 eyes of 79 patients with clear corneal grafts. There were 45 males and 34 females, aged 61.6 +/- 10.2 years. All eyes received penetrating keratoplasty at least 1 year (mean 40.4 +/- 31.3 months) before examination. The normal fellow eyes of 65 subjects were examined as controls. The averaged corneal epithelial permeability of grafted corneas was significantly higher than that of controls (p < 0.001). In the 65 individuals having an otherwise healthy fellow eye, the grafted corneas were significantly more permeable than their control fellow eyes verified by paired t test (n = 65, p = 0.006). Concomitant corneal sensitivity test revealed a significantly hypesthetic cornea. These results show that in spite of a clinically normal clear graft, there is usually a subnormal epithelial barrier function and reinnervation, even years after corneal transplantation. PMID- 7877799 TI - Visualization of human choroidal ganglion cells with the supravital fluorescent dye 4-(4-diethylaminostyryl)-N-methylpyridium iodide. AB - The distribution and morphology of ganglion cell bodies and nerve fibers in supravital human choroidea is studied by staining with the fluorescent dye 4-(4 diethylaminostyryl)-N-methylpyridium iodide (4-Di-2-ASP). We have used the choroids from human donor eyes donated for cornea transplantation. The isolated tissues were rinsed in ringer solution and processed within up to 24 h after death with 3 microM of 4-Di-2-ASP in Ringer for 5-60 min at different temperatures (4-37 degrees C). After incubation, choroid whole flat mounts were observed in a fluorescence microscope. A delicate network of nerve fibers could be distinguished as soon as 5 min after immersion in 4-Di-2-ASP. In addition, labelled ganglion cell perikarya could be seen after longer incubation periods. They occurred individually or grouped in small ganglia of up to 8 cells and were linked together by various processes, which could also be traced to blood vessels. The fluorescent dye 4-Di-2-ASP provides a quick and simple method to visualize the innervation of the human choroid, including local ganglion cells. This nontoxic fluorescent technique will permit further manipulation and electrophysiological investigation of choroidal innervation. PMID- 7877800 TI - Clinical, histological and ultrastructural characteristics of a spontaneous corneal opacity in Sprague-Dawley rats. AB - The eyes of 200 rats (Mol:SPRD, Moellegaard Ltd., Skensvet, Denmark), 8 weeks of age and of both sexes, were examined routinely with a photo-slitlamp microscope (Zeiss) and opthalmoscope (Heine) 3-4 times in the course of four different 12 week toxicity studies. The animals were kept under constant lighting conditions at a room temperature of 20 +/- 2 degrees C and 55 +/- 5% humidity on a standard diet. More than 70% of the animals were found to have more or less prominent corneal opacities already at the beginning of the study. These were morphologically characterized as meshwork-like alterations of the deeper corneal epithelium, mostly located in the central and nasal region. The temporal, upper and lower periphery remained always unaffected. Male animals were more frequently and more intensively affected than the females. The occurrence of the opacity was totally independent of the treatment scheme (controls and drug dosages, respectively), showing a slight increase in density in some of the animals of all groups and remaining stable in others. Regression was rarely observed. Light and electron microscopical investigations demonstrated focal degenerations of the basal epithelial cell layer as well as alterations of its basement membrane. The lesion was not associated with inflammation or irritation. Therefore, we considered that a genetically determined metabolic disorder of the basal epithelial cells might have led to the impairment of basement membrane synthesis. Further screenings performed in conjunction with the breeder evidenced that these opacities are probably caused by a spontaneous mutation with a complex, not X linked genetic background. PMID- 7877802 TI - A statistical analysis of Modified Clinical Technique vision screening of preschoolers by optometry students. AB - Fourth year optometry students screened 745 preschoolers using a slightly altered Modified Clinical Technique (MCT) under the supervision of a faculty doctor. Children who failed the MCT were randomly selected and then matched by age, sex, and ethnic origin to children who had passed the screening battery. The 61 screening failures and 45 matched controls were later given full eye examinations with cycloplegia by University of Alabama at Birmingham faculty doctors who were unaware of the screening results. The positive predictive value (PPV) (0.52) and negative predictive value (NPV) (0.78) of the MCT were calculated directly from the 2 x 2 contingency table crossing screening results and a standard diagnosis. Sensitivity [0.50, k(1,0) = 0.29], specificity [0.79, k(0,0) = 0.30], efficiency [0.70, k(0.5,0) = 0.29] of the MCT, and the prevalence (0.30) of children failing the standard diagnosis were estimated using statistics appropriate to the prospective sampling design. The reproducibility of the diagnosis, estimated by analyzing multiple, independent diagnosis of each study child by seven doctors was moderate (kappa D 0.58). Statistics summarizing the agreement between the MCT and the diagnosis by the individual study doctor are similar to those obtained with comparison to the standard diagnosis. The characteristics of the MCT may be generalized only to similar populations that are screened by clinicians with similar experience, using the same tests. PMID- 7877803 TI - Visual recovery in a patient with Leber hereditary optic neuropathy and the 14484 mutation. AB - Leber hereditary optic neuropathy (LHON) is characterized by an acute, painless, sequentially bilateral reduction in vision that usually occurs in young men. It is a maternally inherited mitochondrial genetic disease. This case report details the chronology of the bilateral vision loss of a patient found to have LHON with a mutation at nucleotide site 14484. A spontaneous recovery of visual acuity and decrease in disability occurred without a corresponding improvement in color vision, contrast sensitivity, or pattern visual evoked potential (VEP's) over a period of 6 years. The abnormal pattern VEP's were one of the indicators of the neural damage to the spatial frequency channels of the visual system. The normal flash VEP's, as determined by the critical frequency of photic driving (CFPD), suggested that most of the fibers in the luminance channels were unaffected by LHON. PMID- 7877801 TI - Vitamin E inhibits retinal pigment epithelium cell proliferation in vitro. AB - Retinal pigment epithelium (RPE) cells migrating through the damaged retina play an important role in the pathogenesis of proliferative vitreoretinopathy (PVR). We found that alpha-tocopherol (vitamin E) inhibits proliferation of human RPE in culture without exerting cytotoxic effects. Maximal inhibition was achieved with 100 microM alpha-tocopherol. Our result could explain the observation that vitamin E supplements have an adverse effect on light-damaged retina and on the course of retinitis pigmentosa. Since it has been shown that supplemental oral administrations of vitamin E can raise the RPE concentration of alpha-tocopherol well above 100 microM and supplementation is not associated with any clinical relevant adverse effect, we believe that vitamin E could be beneficial in the treatment of PVR. PMID- 7877804 TI - The design of a zoom stand magnifier--a new low vision device. AB - A new stand magnifier has been designed for low vision patients and developed into a working instrument. This zoom magnifier has two ergonomic advantages over the currently available single lens magnifiers: it stays in focus (zooms) as the power is changed and it has a longer working space to allow both reading and writing with the same magnifier. This two-lens zoom magnifier contains a stationary plus lens and a movable minus lens. Using a symmetry condition, first order equations are presented and solved for the two lens powers. A family of three zoom magnifiers was designed--low, medium, and high power--each with a conveniently positioned sharp image with a 2-fold range of power and magnification. The equivalent viewing powers of the units (for a +2.50 D add) range from 6 to 23 D. The working spaces are approximately double that of comparable power single lens stand magnifiers. PMID- 7877805 TI - Effect of pattern glare and colored overlays on a stimulated-reading task in dyslexics and normal readers. AB - Scotopic sensitivity syndrome or the Irlen syndrome describes symptoms of asthenopia anamolous visual performance experienced while reading that are lessened by colored filters. One putative explantation for this condition relates to pattern glare: a hypersensitivity to repetitive patterns, including lines of print on a page. Experiment 1 used a placebo-controlled paradigm to investigate the effect of pattern glare and colored overlays on performance at a simulated reading visual search task. Despite the fact that the subjects were university students, the results showed a tendency, of border-line significance, to support the conclusion that colored filters seem to improve reading through ameliorating pattern glare. In experiment 2 we compared the prevalence of pattern glare in matched groups of dyslexic children and good readers. The dyslexic group reported more pattern glare, but also reported more glare from a control stimulus. Pattern glare in the dyslexic group was directly correlated with flicker sensitivity. The results are related to recent research on visual processing and ocular-motor function in dyslexia. PMID- 7877806 TI - Compliance: a comparison of three lens care systems. AB - Noncompliance is an important health care issue. This report presents results of assessments of three different lens care systems and directly compares compliance with each and the potential impact on patients' safety and comfort. Methods involved trained interviewers, patient demonstrations, a panel of experts, statistical analyses, and an assessment of the clinical significance of patients' noncompliant behaviors. These methods were able to discriminate among the levels of compliance with the lens care systems assessed. The three regimens were comparable regarding steps significant to lens wearing comfort with approximately one-third of all patients noncompliant with at least one of these steps. The same cannot be said regarding safety, however, with the incidence of noncompliance at 55, 84, and 91% for the three regimens. These findings indicate that simplicity alone cannot overcome noncompliance and the design of the system is an important consideration when making recommendations regarding lens care. PMID- 7877807 TI - Luminance of projection focimeter target with oblique viewing. AB - In order to test the capacity of an optical projection focimeter for simultaneous use by several observers gathered around the instrument, the luminance of the projected target was measured for 3 projection focimeters (model Axil from Essilor, model LP2 from Nikon, and model LM-P5 from Topcon) when the photometer axis was perpendicular to the instrument screen and at oblique angles up to 75 degrees in 5 degrees increments. As expected, the luminance of the target decreased as obliquity of viewing increased; however, the rate of reduction is characteristic of each focimeter model. The repeatability of dioptric measurements with the Axil focimeter was assessed in the usual viewing position when the luminance of the target was reduced by optical filters (neutral density varying from 0.2 to 1 in 0.2 steps). The repeatablity remains within +/- 0.05 D for optical densities < or = 0.8. Our results show that a useful luminance is maintained over an observation angle that extends to 45 degrees. Depending on the model of focimeter, several observers may simultaneously observe and judge the focusing of the instrument. PMID- 7877808 TI - A note on the accuracy of inexpensive light meters for measuring luminous transmittance. PMID- 7877809 TI - [Thrombolysis in acute myocardial infarct]. AB - The indications, method, results and complications of various thrombolytic medical treatment options in acute myocardial infarction is discussed. The thrombolytic treatment decreases the in-hospital and late mortality of patients and prevents the deterioration of left ventricular function. The earlier the treatment is initiated, the better result may be expected. The indication of thrombolysis may be expanded for patient with left bundle branch block, higher age groups, and also for late admissions after the onset of chest pain. PMID- 7877810 TI - [Surgical treatment of pulmonary metastases from colorectal tumors]. AB - Authors analysed 25 colorectal cancer lung metastases. Among them were 13 male 12 female. Ages ranged from 45 to 70 years. The lung nodules were discovered without any symptoms in 19 cases. The disease was localized on the right in 16 patients, in 7 on the left side and 2 others were bilateral. There were 19 solitary and 6 multiple nodules. In two-third of the cases developed metastases within 3 years of colorectal interventions. In 23 cases was performed partial lung resection (wedge or lobectomy) except one pneumonectomy. In one of the patients lung biopsy was just carried out. A case presentation is detailed where the right upper lobe metastasis was resected by videothoracoscopic method. They observed no postoperative mortality. The cumulative five year survival rate is 28% (for solitary lesions 31.6%, for multiple nodules 17%). PMID- 7877811 TI - [Comparative study of antibiotic consumption in Hungarian hospitals during 1989 1991]. AB - The data of case histories of the year of 1989 of seven Hungarian hospitals and also the 1990 and 1991 data of two hospitals were collected and integrated in a database. Consumption of antibiotics were represented in DDD (Defined Daily Dose)/1000 hospital day. These data were compared with the data of the drugs delivered by the hospital pharmacy in one of the mentioned hospitals between 1989 and 1992. It was concluded that data based on case histories represent better the real antibiotic consumption than those of the hospital pharmacy. Reason of this phenomenon is the fact, that considerable amount of drug supply gets out of institutions. Great differences were observed between the seven hospitals in the total amount of antibiotic consumption and between the different antibiotic groups as well. Drugs most frequently used were tetracyclines, broad spectrum penicillins, sulfonamides and aminoglycosides. Consumption of penicillins was decreasing. Regarding new drugs only utilisation of quinolones was increasing. It was concluded, that structure of antibiotic selection did not follow the recommendations of the medical literature. The authors suggest that "antibiotic policy" should be introduced in Hungarian hospitals so as to imporve antibiotic utilisation. PMID- 7877812 TI - [Misunderstandings and pitfalls on the narrow pathway of medical ethics]. AB - Due to the scientific progress and the rapid changes in social circumstances, medical ethics became a complicated and difficult science. On the basis of fundamental and simple principles of medical ethics (salus aegroti suprema lex) the author tries to take standpoint in questions arisen in his practice in which the medical aspect was not necessarily obvious. It can be ethically faulty when more then necessary is provided to the patients (in prescribing medicine, in welfare, in performing examinations). It is necessary that the steadily increasing medical specialization goes together with the better cooperation between the medical disciplines and with wider distribution of special experience. The system of the medical honorarium should be entirely open and publicly regulated. It is a medical ethical obligation to place the organs of brain death cases suitable for transplantation at the disposal of patients requiring it. In the field of reproduction not the suspicion alone but the undoubtebly proven injury of fetus only can be a sufficient medical indication for the termination of pregnancy. The medical person by his attitude in creating optimal conditions for the perinatal care has to do his best in avoiding any heartlessness, contralily, in promoting willingness in the parents to have children. PMID- 7877813 TI - [Personal view on the Index of Hungarian Medical Literature"]. PMID- 7877814 TI - [Primary endoscopy of the stomach]. PMID- 7877815 TI - [Surgical excision of tracheal and bronchial tumors after endobronchial Nd-YAG laser photocoagulation]. PMID- 7877816 TI - [Hormone substitution in menopause]. AB - Menopause and related symptoms are direct consequences of insufficient ovarian oestrogen production. During the last two centuries women life expectancy increased from 48 to 79 in developed countries resulting a 20 years periods without proper hormone support. Extraovarian steroid production and its effects are presented. The role of hormone replacement therapy (HRT) and locally aviable products discussed. PMID- 7877818 TI - [Effect of menopause on carbohydrate metabolism]. AB - Endocrine alterations in menopause produce disadvantageous changes in the carbohydrate and lipid metabolism. The character and tendency of these alterations are very similar to those found in type II diabetes mellitus. The abdominal visceral fat content as well as the blood level of cholesterol, triglyceride, glucose and insulin increase in postmenopause. These changes can be advantageously influenced by hormone replacement therapy. PMID- 7877817 TI - [Cardiovascular diseases and hormone replacement therapy in females]. AB - The effects of hormone replacement therapy are summarized from the point of view of ischaemic heart disease and stroke syndrome. The beneficial effects of oestrogen or combined oestrogen-gestagen therapy on different lipid parameters, some factors of the haemostasis are discussed, as well as the possibilities of a direct effect on blood vessels. Hormone replacement therapy in the menopause significantly decreases cardiovascular and stroke morbidity and mortality. PMID- 7877819 TI - [Survey of the most important facts known about osteoporosis]. PMID- 7877820 TI - [Psychoendocrinology of menopause]. AB - The possible role of of the marked changes in the regulation of female sex hormones has been implicated in the higher prevalence rate of anxiety and affective disorders in women. There is no evidence, however, for a direct relationship between specific hormone alterations and psychiatric, nosologic entities in the critical periods (premenstrual, postpartum, menopausal). The menopausal psychosyndrome can develop as a result of a chain reaction triggered by the fairly universal and specific vasomotor symptoms: hot flushes and night sweats. The hormone substitution therapy of menopause may have a prompt effect both on the somatic and psychic symptoms, by suspending the domino effect. In addition to that oestrogen has some activating and mood elevating effect, while progesteron can reduce anxiety and related symptoms. PMID- 7877821 TI - [Should estrogen replacement therapy be applied in women with genital and breast cancer?]. AB - In this country, hormone replacement therapy (HRT) has been used more extensively in the last few years. The benefits of HRT in cardiovascular diseases, osteoporosis and quality of life has been well established. Breast cancer and endometrial carcinoma have been considered as contraindications for HRT. A reappraisal of this practice is necessary since we have no evidence that HRT may adversely influence the outcome of these tumours. Nevertheless, theoretically this is possible because the effect of estrogens on occult metastases in unknown. The relationship between replacement therapy and the uterine sarcomas is of particular concern. HRT is safe in patients successfully treated for carcinoma of the vulva, vagina, uterine cervix and in those with ovarian cancer. Experience suggests that the estrogen can also be used safely in women treated previously for endometrial cancer. As far as breast cancer is concerned it appears logical to discuss the risk-benefit considerations with our patients before embarking on using HRT. Consultation with a gynaecological oncologist prior to HRT in patients with endometrial and/or breast cancer is strongly recommended. PMID- 7877822 TI - The aging substantia nigra: quantitative histologic study. AB - In this study, we estimated the amount of neuronal neuromelanin in hematoxylin and eosin sections of the pars compacta of the substantia nigra in 69 autopsied subjects, 14 to 100 years old. The mean area of cellular neuromelanin showed a curvilinear increase from 103 microns2 at age 14, to 600 at age 67 before dropping off to 328 at age 100 (R2 = +0.51, p < 0.00001). By contrast, the areal fraction or area of neuromelanin relative to the area of neuronal cell bodies showed a linear increase with age (r = +0.84, p < 0.00001). The latter and an increase in the percent of neuromelanin pigmented neuronal cell bodies from 83% at age 14 to almost 100% at age 65 and older (R2 = +0.61, p < 0.00001) accounted for the increasing mean area of cellular neuromelanin. By contrast, a decrease in the mean area of neuronal cell bodies (r = -0.63, p < 0.00001) and a decrease in the number of profiles of neuronal cell bodies (r = -0.51, p < 0.0001) explained the decrease of mean area of cellular neuromelanin beyond 67. Our findings support the hypothesis that an overload of neuromelanin is neurotoxic and emphasize the importance of using age-matched controls in histopathologic studies of the substantia nigra. PMID- 7877823 TI - Evaluation of left ventricular diastolic function in insulin dependent diabetic children by M-mode and Doppler echocardiography. AB - To evaluate the presence of diabetic cardiomyopathy, we measured various parameters of left ventricular systolic and diastolic function by means of M-mode and Doppler echocardiography in 50 IDDM children (mean age 13 +/- 3 years; mean IDDM duration 5.9 +/- 4.1 years) free of cardiovascular symptoms. As compared to age-matched healthy control subjects, diabetic children evidenced a significant increase in mean values of pressure half time (PHT), an index of the early diastolic phase (53.7 +/- 10.2 msec vs 44.5 +/- 9, p < 0.002). When the patients were subdivided on the basis of IDDM duration, metabolic control and the presence of retinal microangiopathic abnormalities, those with longer IDDM duration and poor glycemic balance had higher PHT values. These data indicate that an early diastolic dysfunction, expressed by reduced left ventricular compliance, can be found in children with Type 1 diabetes mellitus of relatively short duration. Doppler echocardiography is a reliable non-invasive means to assess early impairment of cardiac function in IDDM patients. PMID- 7877824 TI - Esophagocardiomyotomy with Dor gastroplasty in the treatment of esophageal achalasia. AB - Thirteen patients affected by achalasia of the esophagus, undergoing esophagocardiomyotomy with Dor gastroplasty, are reported. No postoperative deaths or complications occurred. Overall long-term results were satisfactory: excellent or good in 92.3% of cases, fair in 7.7%. Manometry after esophagocardiomyotomy as compared to preoperative assessment showed a decreased resting pressure in the esophageal body, in all patients in whom it was elevated, and the appearance of some peristaltic waves in 23.1% of them (3 patients). As for lower esophageal sphincter, some relaxation after deglutition was observed in one patient. The 24h pH monitoring showed signs of gastroesophageal reflux only in one patient. Based on the obtained results which compare well with those of the literature, the authors be believe that the procedure represents an effective treatment of esophageal achalasia. PMID- 7877825 TI - Clinical application of 131I-HIPDM in the patients with chronic obstructive pulmonary disease. AB - N,N,N'-trimethyl-N'-2 hydroxy-3-methyl-5-iodobenzyl-1,3-propanediamine iodine-131 (HIPDM) as a lung imaging and metabolic tracer in patients with chronic obstructive pulmonary disease (COPD) were used. 0.4 mCi 131I-HIPDM was rapidly injected into the antecubital vein. The imaging of 131I-HIPDM in the lung was different in various groups. 131I-HIPDM of the clearance by the lungs was a biphasic curve (rapid phase and slow phase). It was displayed that rapid phase of the clearance curve of 131I-HIPDM in the lungs in subjects with chronic obstructive pulmonary emphysema, especially those of smokers were very slow. The rapid phase of the 131I-HIPDM of the right lung clearance was significantly correlated with Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), Functional Residual Capacity (FRC), Residual Volume (RV), Total Lung Capacity (TLC) p < 0.01; Peak Expiratory Flow Rate (PEFR), Vital Capacity (VC), Maximum Ventilatory Volume (MVV), Arterial oxygen tension (PaO2) p < 0.05. Smoking influence on clearance of 131I-HIPDM of the lung including normal smokers with normal lung function. It was considered that the analysis of the lung release of 131I-HIPDM forms a new lung dysfunction index and it was useful that found early lung damage. PMID- 7877826 TI - Prolonged lung retention of 131I-HIPDM in smokers. AB - Thirty-five subjects were divided into 4 groups; the first group was composed of 8 healthy nonsmoking subjects; the second group included 8 healthy smokers; the third group included 12 nonsmoking patients suffering from chronic obstructive pulmonary emphysema; the fourth group was composed of 7 smokers with chronic obstructive pulmonary emphysema. N,N,N'-trimethyl-N'2-Hydroxy-3-Methyl-5 iodobenzyl-1,3-propanediamine iodine-131(HIPDM) was rapidly injected into the antecubital vein. The influence of 131I-HIPDM by lung clearance was analysed thought imaging of lung and ratio of prolongation of 131I-HIPDM in the lung. Prolongation of 131I-HIPDM in the lung was shown in the smokers with chronic obstructive pulmonary emphysema in 60 minutes, and the healthy smokers, smokers with chronic obstructive pulmonary emphysema in the 24 hours after the injection of 131I-HIPDM. Smoking is an important factor of disturbance of lung clearance. PMID- 7877828 TI - Obesity: internal medicine, obstetric and gynecological problems related to overweight. AB - Obesity is the major nutritional problem affecting industrialised society. According to a recent ISTAT survey, 41% of men and 19% of women in the Italian population suffer from obesity. Obesity is a complex pathological entity with a multiform and often indeterminable etiology. Studies of natural and adopted children and twins suggest that a clear hereditary, constitutional predisposing factor is present in obesity which interacts with environmental conditions. The genetic factor is also suggested by the statistical finding that if neither parent is obese, then only 7-10% of their children will be obese, whereas if one parent is obese, 40-50% of children will probably become obese, and if both parents are obese as many as 70-80% of children will be obese. The risks related to obesity can be broadly categorised as mechanical and metabolic. The former include arthrosis, osteoporosis, degenerative diseases affecting the joints and bone matrix, muscular hypotrophy and respiratory deficits. The major metabolic risks include hypercholesterolemia, altered glycoregulation and hyperuricemia. From an obstetric point of view, apart from the fact that obesity is often associated with sterility, excess weight can often lead to sometimes dramatic complications during pregnancy, involving major risks for both mother and fetus. From a gynecological point of view the links between obesity, tumours and menopause are well known. PMID- 7877827 TI - Sudden death in diabetic subjects: evidence for a peculiar circadian variation in occurrence. AB - Anatomo-physiopathological and chronobiological features of 59 diabetic subjects out of 610 non hospitalized individuals observed for sudden death (SD) in an Emergency Room, over an 8-year period, were studied. Mean age and anatomopathological causes of SD were not different between diabetic (DMs) and non-diabetic subjects (NDs). However the frequency of DMs was higher among subjects who died from circulatory failure death (CFD), rather than from arrhythmic death (AD). Diabetics presented a prevalent peak incidence of SD in the afternoon-late evening; whereas in NDs two peaks were present, respectively in the morning and in the afternoon. According to anatomo-physiopathological causes, DMs presented a higher incidence of acute myocardial infarction (AMI) and CFD between 21:01 and 24:00, whereas in NDs the prevalent peak of AMI was observed in the early afternoon (13:01 to 16:00). Moreover, in DMs SD from acute myocardial failure prevalently occurred in the early afternoon (13:01 to 16:00), whereas in NDs it was uniformly distributed throughout the day. The present study seems to indicate that different anatomo-physiopathological causes of SD may present specific temporal patterns in diabetics. PMID- 7877829 TI - Efficacy of Fat Mobilisation System (FMS) in the treatment of obesity and its utility in the resolution of gynecological problems related to overweight. AB - In industrialised countries the problem of overweight affects more than 50% of the adult population. Knowledge acquired over the past years has replaced the principally esthetic concept of obesity with the notion of a multifactorial pathology, the outcome of an imbalance in the individual's energy balance caused by an excessive food intake as well as an inadequate energy consumption. The Fat Mobilisation System (FMS), which is able to activate a fat clearance process following cold local application, has proved a valuable and well tolerated tool capable of influencing the entire system responsible for obesity. A group of 109 patients of both sexes, aged between 15 and 71 years old, with problems of overweight and/or figure faults linked to the localised accumulation of fat, underwent out-patient treatment in the form of bandaging with elasticated bandages soaked in active solution able to lower body temperature by 2-3 degrees C. The results were satisfactory in all cases. In particular, a group of 24 women (10 of a childbearing age, 7 in premenopause and 7 in menopause), in whom overweight was associated with gynecological problems, were evaluated by Department A of the Department of Gynecology and Obstetrics at the University of Turin. An improvement in gynecological symptoms was achieved in parallel to weight loss in all patients. PMID- 7877830 TI - Postnatal development of intestinal villi in the rat. Determination of villus size gradient. AB - The existence of the so called "Villus Size Gradient" (VSG) which defines the proportional decrease in height of intestinal villi from duodenum to ileum is well documented in adult animals and man. The aim of this study is to define whether the VSG is present since birth or, if not, when and why it appears. We have measured the height of intestinal villi in 25 rats: 5 at 1 day from birth, 5 at 5 days, 5 at 8 days, 5 at 15 days and 5 at 30 days. We have prepared histological slides of a duodenal, jejunal and ileal tract of each animal and measured the height of villi on microphotographs. At day 1 we observed a higher size of duodenal villi statistically significant with respect to jejunum and ileum, while at day 5 no differences were observed between the various intestinal tracts. The VSG become evident 8 days after birth progressively increasing to day 30. The predominance of duodenum present at birth is therefore probably due to the fetal developmental growth which is known to be more precocious in duodenum than in more distal tracts. Five days after birth the intestinal villi are equally developed, while in later ages the VSG appears. So we can conclude that the VSG is a consequence of luminal and humoral factors and not a predetermined event. PMID- 7877831 TI - Is tumour necrosis factor alpha the molecular basis of concomitant immunity in schistosomiasis? AB - Prior to the development of high levels of resistance to infection with schistosomes, some mechanism appears to limit the number of productive worms in individuals, since children do not become superinfected, despite continued exposure to infection. One way in which infection levels might be limited, is through the generation of a concomitant immunity. Concomitant immunity results in the destruction of newly invading schistosomula whilst established adult worms continue to survive. Recent studies have provided evidence that TNF alpha enhances worm fecundity and is essential for granuloma formation. TNF alpha may therefore be important in worm reproduction and transmission, since the granuloma may serve to assist the passage of the eggs out of the tissues. With the additional evidence that the cytotoxic activity of lymphokine-activated macrophages against schistosomula may be, at least in part, due to the action of TNF alpha, we propose that TNF alpha may also be responsible for the phenomenon of concomitant immunity. PMID- 7877832 TI - Immune killing of newborn Trichinella larvae by human leucocytes. AB - The capacity of human leucocytes from normal donors to kill the newborn larvae of the nematode Trichinella spiralis in vitro, in the presence of serum from infected individuals, was studied using newborn larvae (NBL) less than 2 h of age or NBL that had been maintained in culture at 37 degrees C for 20 h. Neutrophils and monocytes attached to newborn Trichinella larvae and killed them, regardless of their age. When eosinophils were used, 20 h old NBL were killed whereas 2 h old NBL were not. Complement was essential in the cytotoxic effect of leucocytes. These results indicate that host defence against T. spiralis in humans may be a complex mechanism in which different cell types can be involved. They also show that the age of maturation of the NBL is of paramount importance in the antibody dependent cellular cytotoxicity reaction. PMID- 7877833 TI - Defective mucosal immunity and normal systemic immunity of Mongolian gerbils, Meriones unguiculatus, to reinfection with Strongyloides venezuelensis. AB - The systemic and local protective activity of Mongolian gerbils was examined after re-infection with Strongyloides venezuelensis. Mongolian gerbils were unable to expel S. venezuelensis adult worms from the intestine for over ten weeks after a primary infection. Therefore, immune animals were prepared by treating with mebendazole four weeks after a primary infection and then they were challenged by different maturation stages of the parasite; subcutaneous inoculation with the infective larvae (L3) obtained by faecal culture, oral administration of L3 obtained from the lungs of rats three days after a primary infection, or oral implantation of adult worms obtained from the intestines of rats seven days after a primary infection. The results show that, although immune animals were highly resistant against challenge infection by subcutaneous inoculation with cultured L3, they were unable to expel orally administered lung recovered L3 nor orally implanted adult worms. Although potentiated mastocytosis was induced by challenge infections with lung-recovered L3 and adult worms, all mast cells were formalin-resistant, heparin-containing cells and never seen in the epithelial layer. In spite of the defective protective capacity at the intestinal mucosa, circulating antibody production specific to S. venezuelensis adult as well as L3 antigen was positive. Therefore, the inability of Mongolian gerbils to expel S. venezuelensis adult worms from the intestine seems to be due to the defects of effector/regulator cells, presumably mast cells, but not due to immune unresponsiveness to parasite antigen. PMID- 7877834 TI - Pulmonary immune responses to Nippostrongylus brasiliensis: isotype-specific antibodies in bronchoalveolar lavage fluids of rats. AB - Larvae of Nippostrongylus brasiliensis have an obligatory migratory phase through the lungs of rats during their development. Since earlier studies have shown that this migration is associated with accumulation of Fc receptor bearing effector cells in the bronchoalveolar spaces, we have analysed antibody reactivity in bronchoalveolar lavage fluids (BALF) during development of immune responses against N. brasiliensis. The development of parasite specific antibodies in bronchoalveolar spaces was similar to that in the serum, but was of a lower titre. A secondary infection resulted in an anamnestic response. Isotype analysis showed that IgG, IgA and IgM antibodies were present in BALF and they recognized several proteins of the parasite ranging from 16-290 kDa. Immunoblot analysis on two-dimensional electrophoretic separated parasitic proteins identified stage specific differences in the BALF antibody responses. IgG was the predominant class of antibody in BALF and when compared with serum, IgM antibody responses were weak. Thus, infection with N. brasiliensis resulted in the appearance of site-, stage- and isotype-specific antibody responses in the lungs of rats. PMID- 7877835 TI - A theoretical framework for immune responses and predisposition to helminth infection. AB - Many field studies of human helminth infections have reported a positive correlation between parasite burdens and the rate of re-establishment of infection following chemotherapy, i.e., predisposition. Some studies have also reported the relationships between re-establishment and exposure and immune responses. The interpretation of these data is made difficult by the complexity of the underlying immunoepidemiological processes. In this paper, simple mathematical models are used to explore expected patterns, especially in relation to host age. These patterns are determined by rates of infection, parasite life expectancy, the level of immunological responsiveness, the duration of immunological memory, and may be greatly affected by the immunogenic roles of different parasite stages. In general, acquired immunity is predicted to reduce the degree of predisposition. This reduction is age-dependent and may generate 'negative predisposition' in some age classes. Age-dependent reductions in the correlation between re-establishment and exposure are also predicted. The correlation between re-establishment and protective immune responses is also predicted to be age-dependent, but may remain positive for all ages despite significant acquired immunity. The results suggest that great care is needed in the interpretation of immunoepidemiological data from treatment-reinfection studies. PMID- 7877836 TI - Correlations between worm burden and markers of Th1 and Th2 cell subset induction in an inbred strain of mouse infected with Trichuris muris. AB - Helper T cell subset induction was examined within a single inbred strain of mouse (B10.D2/n) where individuals varied in their ability to expel the nematode parasite Trichuris muris. In this mouse strain approximately half of infected individuals resist infection whilst half are unable to expel the parasite and harbour chronic mature adult worm infections. We here assess various T cell and serological parameters in individual B10.D2/n mice infected with T. muris in relation to the number of parasites harboured. Worm burdens showed very significant negative correlations with five different parameters indicative of the selective expansion within the host of helper T cells of the Th2 subset. Thus, in vitro IL-5 and IL-9 production by restimulated mesenteric lymph node cells, total IgE levels, the early parasite-specific IgG1 response (all P < 0.01) and intestinal eosinophilia (P < 0.05), were all significantly negatively correlated with worm burden. In addition, levels of IL-3 were significantly greater in mice resistant to infection (P < 0.01). In contrast there was a significant positive correlation between worm burden and parasite-specific IgG2a levels (P < 0.05), IgG2a production being under the tight control of the Th1 specific cytokine IFN-gamma and thus a reliable marker for in vivo Th1 cell activation. The data demonstrates that an individual infected with T. muris is capable of mounting either a protective Th2-type response or an inappropriate Th1 type response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877837 TI - Schistosoma mansoni: genetic non-response to p40, the major protein antigen of the egg, reveals a novel mechanism enhancing IgM production during infection. AB - p40 is the major protein antigen in eggs and miracidia of Schistosoma mansoni. Immunization with recombinant p40 produced in bacteria and with p40 from miracidia reveals a conventional immune response gene effect in which H-2b mice fail to produce antibody against p40. This is true when either denatured recombinant p40 and non-denatured miracidial p40 are used as immunogens. In contrast, during infection all strains of mice produce antibodies to p40. However, non-responder H-2b mice produce only IgM to p40 and never any IgG. Thus, H-2b mice appear to be producing specific IgM to p40 in the absence of MHC restricted T-cell help. The mechanism revealed in these non-responder mice might play an important role in stimulating the production of IgM 'blocking' antibodies to antigens from schistosomula which cross-react with egg antigens. PMID- 7877838 TI - Arginine-dependent generation of reactive nitrogen intermediates is instrumental in the in vitro killing of protoscoleces of Echinococcus multilocularis by activated macrophages. AB - The interaction between protoscoleces of Echinococcus multilocularis and activated murine macrophages was examined in this study. Marked protoscolicidal activity was displayed by peritoneal macrophages (PM) activated with interferon gamma (IFN-gamma), or IFN-gamma plus lipopolysaccharide. Pretreatment of the parasites with heat-inactivated specific murine infection serum, but not with normal serum rendered them more susceptible to PM killing. NG-monomethyl-L arginine, a competitive inhibitor of L-arginine completely inhibited the killing activity of activated PM, while reconstitution of arginine-free medium with L arginine restored the killing properties of the activated PM. The results show that activated PM have the ability to kill E. multilocularis protoscoleces in vitro and suggest that reactive nitrogen intermediates (RNI) play an important role in the mechanism. An oxygen-mediated mechanism did not appear to play a role because scavengers of reactive oxygen species did not reduce the killing activity. The arginine-dependent killing mechanism was enhanced by superoxide dismutase (SOD), probably because SOD might prolong the effect of nitric oxide. Secretion of RNI by activated macrophages may be capable of a significant role in preventing of the dissemination of E. multilocularis infection in vivo. PMID- 7877839 TI - Stage-specific surface antigens of the cattle lungworm Dictyocaulus viviparus. AB - Immunofluorescence on live Dictyocaulus viviparus parasites revealed a significant antibody response by vaccinated and patently infected bovine hosts to the sheath of infective larvae (L3), a structure which is generally thought to be shed from the parasite surface prior to invasion of host tissue. In contrast, surface-exposed antigens of the adult, egg and pulmonary L1 stages were recognized only by serum antibody from calves exposed to a patient lungworm infection. Radioiodination of sheathed L3 identified a restricted set of components while a more complex pattern of labelled material was observed with adult parasites. Many more components of adult worms were labelled by the Bolton Hunter than by the Iodogen reagent, probably reflecting the more penetrative labelling propensities of the former. Stage-specificity of surface-associated antigens of adult parasites was demonstrated by their immunoprecipitation by antibody from patently-infected, but not from vaccinated, calves. There was no in vitro release of the major iodinatable surface-associated antigens of adult parasites not any binding of antibody raised against adult excretory-secretory (ES) products to the surface of living adult worms, suggesting that surface components do not contribute to adult ES products in this species. Antibody responses to the surface of adults, L1 and eggs were specific to patently infected animals and may provide a useful indicator of exposure to patent infection. PMID- 7877840 TI - Murine tumour necrosis factor plays a protective role during the initial phase of the experimental infection with Trypanosoma brucei brucei. AB - Soluble extracts from salivarian trypanosomes (Trypanosoma brucei brucei, T. evansi and T. congolense) were shown to be capable of inducing murine tumour necrosis factor (mTNF) secretion, both in vivo and in vitro, whereas the soluble extract of an intracellular trypanosome (T. cruzi) failed to do so. Furthermore, the role of mTNF during the initial phase of experimental infections with T. brucei was studied by treating infected mice with mTNF-inducing trypanosoma soluble extract and with neutralizing monoclonal anti-mTNF antibodies. Treatment of the infected animals with different doses of T. brucei soluble extract resulted in a lower first parasitaemia peak (low lysate dose) and in a longer survival time or in a nearly total inhibition of parasite development (high lysate dose). Cotreatment of the infected mice with both anti-mTNF antibodies and a high dose of soluble extract completely restored the parasite development in both trypanosusceptible C3H/He mice and trypanosubtolerant CBA Ca mice, indicating a protective role of mTNF during the parasitaemia. Collectively these results suggest a negative influence of mTNF on T. brucei development in vivo. PMID- 7877841 TI - Different susceptibility to the IL-3 induced-protective effects between Strongyloides ratti and Nippostrongylus brasiliensis in C57BL/6 mice. AB - Repetitive administration of recombinant IL-3 induced protection against Strongyloides ratti but not against Nippostrongylus brasiliensis in C57BL/6 mice. Numbers of S. ratti were negligible from day 4 to day 6 post-infection in mice injected with IL-3, whereas N. brasiliensis burdens were almost equal from day 4 to day 6 between mice injected with IL-3 or with medium. Mice treated with IL-3 and then concurrently infected with S. ratti and N. brasiliensis were protected from intestinal S. ratti but not from N. brasiliensis. The numbers of intestinal mucosal mast cells were increased by the repetitive IL-3 treatment on one day after the final injection and was augmented by subsequent infection with both nematodes. PMID- 7877842 TI - Reduced microbicidal and anti-tumour activities of human monocytes after ingestion of Plasmodium falciparum-infected red blood cells. AB - Oxidatively stressed red blood cells (RBC) and Plasmodium falciparum-infected RBC (PRBC) are avidly phagocytosed by human peripheral monocytes. Following the ingestion of PRBC the monocytes' ability to phagocytose PRBC and to generate aggressive oxidative compounds is severely impaired. In the present work the microbicidal and anti-tumour capacities of monocytes fed with diamide-treated RBC and PRBC harbouring mature (trophozoite) parasites have been investigated. The capacity of the latter, but not of the former, to phagocytose Escherichia coli and Staphylococcus aureus and to kill them, as well as ingested Candida albicans cells intracellularly, was found to be markedly impaired. Monocytes that have ingested PRBC had a significantly reduced cytostatic and cytolytic activities against a lymphoblastic tumour cell line. Monocytes fed with oxidatively stressed RBC had normal or sometimes even greater anti-tumour activities. Monocytes that have ingested PRBC showed a reduced capability to produce superoxide following stimulation with phorbol ester. Such impairment in monocyte functions may explain the reduced antibacterial and anti-tumour activities of monocytes in malaria patients, and could be consequential to their ability to resist bacterial infections and to provide means for the control of tumour development in those patients. PMID- 7877843 TI - Comparison of the hepatoprotective effects of immune cells and serum in Schistosoma mansoni-infected immunosuppressed mice. AB - Immunosuppressed mice with heavy Schistosoma mansoni infections suffer from a severe hepatotoxicity reaction soon after the onset of infection patency, and this may be directly consequent upon the failure of the hosts to mount adequate granulomatous responses to embolized parasite eggs. Immune serum or immune peripheral lymphocytes from normal S. mansoni-infected immunologically intact donor mice were transferred to homologously-infected syngeneic T-cell deprived recipients to test the respective capacities of the transferred humoral or cellular immune effector elements to prevent hepatocellular damage and to reconstitute granuloma formation. Transferred immune serum was very effective in preventing liver cell damage, but did not significantly reconstitute the capacity to form granulomas in the recipients. In contrast, mice receiving immune spleen and mesenteric lymph node cells had their capacity to form granulomas around liver-bound eggs reconstituted, but lymphoid cell transfer was less effective in protecting against hepatocyte damage than serum transfer. Protection of host tissues may therefore not be the main role of the T-cell mediated S. mansoni egg granuloma. PMID- 7877844 TI - The role of OX22- helper T cells in protective immunity to reinfection with Taenia taeniaeformis in rats. AB - Spleen cells (SpC) and mesenteric lymph node cells (MLNC) from F344 donor rats actively immunized by oral inoculation with Taenia taeniaeformis eggs were syngeneically transferred into previously uninfected recipient rats by intravenous injection. Recipient rats were challenged with eggs after cell transfer. The degree of immunity was assessed by counting the number of growing metacestodes (MC) in the liver and compared with that in controls. Transfer of 2 x 10(8) SpC, obtained from donors immunized for ten or more (but not for three or five) days before cell transfer inhibited the establishment of most of MC. There were approximately 86-88% reductions in MC recoveries. SpC (2 x 10(8)) obtained from donors immunized for ten days inhibited the establishment of most of MC in recipient rats when transferred nought, two, or 24 h (but not 48 h) before egg challenge. Functional cells in the immune SpC were helper T cells W3/25+, OX8- and OX22-. However, immune MLNC obtained from donors immunized for three to ten days before cell transfer had no effect on transferring immunity. PMID- 7877845 TI - Trypanosoma cruzi upregulates nitric oxide release by IFN-gamma-preactivated macrophages, limiting cell infection independently of the respiratory burst. AB - The relationship between nitric oxide (N = O) produced by mouse peritoneal macrophages (MPM) and Trypanosoma cruzi infection is still poorly understood. The conditions of MPM activation by gamma-interferon (IFN-gamma) to trigger a N = O dependent trypanocidal activity, as well as the effect of parasite infection or of reactive oxygen species (ROS) inhibitors on the N = O release were studied. T. cruzi infection occurring after a previous 24 h MPM activation induced an enhancement of nitrite levels (the stable degradation product of N = O) in cell supernatants; both the percentage of infected MPM and the number of amastigotes per infected cell were decreased in comparison to infected but non-activated MPM. Addition of superoxide dismutase or catalase to non-infected but activated MPM increased the nitrite levels; these were not detectable when L-arginine inhibitors were added together with ROS inhibitors. The latter had no effect on infection nor on nitrite levels when infection occurred after pre-activation, and induced only a weak nitrite release when infection took place before MPM activation. Altogether, these results support the involvement of N = O in the inhibition of T. cruzi infection by IFN-gamma-preactivated macrophages, together with the upregulation of N = O release by T. cruzi infection independently of the respiratory burst. PMID- 7877846 TI - Mechanisms of eosinophilia in Toxocara canis infected mice: in vitro production of interleukin 5 by lung cells of both normal and congenitally athymic nude mice. AB - Mechanisms of eosinophilia were compared between in vitro bone marrow cell cultures of congenitally athymic (nu/nu) mice and their heterozygous littermates (nu/+). Cultures of 5 x 10(4) bone marrow cells using interleukin 3 (IL-3), IL-5 and granulocyte-macrophage colony-stimulating factor showed that nu/nu and nu/+ mice mimicked each other in eosinophil production both before and after infection with Toxocara canis. Eosinophil differentiating activity (EDA) was detected in media conditioned by spleen cells and lungs of T. canis infected nu/+ mice, although nu/nu mice showed EDA only in lung-conditioned medium. EDA, detected both in infected nu/nu and nu/+ mice, was inhibited by an anti-IL-5 monoclonal antibody. These results indicate that IL-5 may be produced by lung cells of both nu/nu and nu/+ mice as well as by spleen cells of nu/+ mice infected with T. canis, which is the reason why nu/nu mice infected with T. canis exhibit blood eosinophilia. PMID- 7877847 TI - Antibody to interleukin 5 prevents blood and tissue eosinophilia but not liver trapping in murine larval toxocariasis. AB - Mice previously sensitized by infective-stage larvae of the canine nematode, Toxocara canis, trap large numbers of challenge larvae within the liver; trapped larvae are found within eosinophilic granulomas. To investigate the role of eosinophils in this phenomenon we examined larval trapping in mice depleted of blood and tissue eosinophils by treatment with a monoclonal antibody (MoAb) (TRFK 5) produced against recombinant murine interleukin 5 (rmIL-5). Control mice received either an isotype-matched control MoAb or PBS. On day 0 test mice were given a sensitization dose of 125 infective T. canis eggs. Test and challenge control mice received 500 infective eggs on day 28. All mice were killed on day 42 and larval numbers within the liver were determined. Liver samples were also collected for histopathological and morphometric examination. When compared to test mice treated with PBS or the isotype control, the level of circulating eosinophils in anti-IL-5-treated test mice was reduced by 94-96% on days 14 and 27, 99% on day 35, and 100% on day 42; the level of tissue eosinophils within liver granulomas on day 42 was reduced by 92-95%. The total area of inflammation within the liver was similar among all test groups. However, the highly eosinophilic infiltrates, present in control sections, were replaced in anti-IL-5 treated mice by lymphocytes, macrophages, and foreign-body giant cells. No difference was found in larval trapping between antibody-treated groups. These findings suggest that the eosinophil is not necessary for liver trapping in murine larval toxocariasis. PMID- 7877848 TI - In vitro secretion of cytokines by human mononuclear cells of individuals during and after cutaneous leishmaniasis infection. AB - Human peripheral blood mononuclear cells were incubated in the presence of Leishmania major promastigotes. The culture supernatants were collected after 24 and 72 h and the cytokine content was measured. It was found that mononuclear cells from cured individuals, in the presence of L. major promastigotes, had increased leishmanicidal activity and secreted increased levels of interferon gamma (IFN gamma), interleukin-2 (IL-2) and tumour necrosis factor alpha (TNF). The levels of IL-6, on the other hand, did not differ from the levels secreted by cells from unexposed individuals. The secretion of cytokines by cells from patients in the course of the disease was sometimes elevated, but the pattern they presented was more heterogeneous than that of cured individuals, and showed less correlation with leishmanicidal effector activity. Addition of IFN and IL-2, but not TNF, to cultures from unexposed individuals caused increased leishmanicidal activity, suggesting that these factors play a role in controlling the parasite infection; the role of TNF is not yet clear, and is probably concentration-dependent. PMID- 7877849 TI - A longitudinal study of naturally acquired cellular and humoral immune responses to a merozoite surface protein (MSP1) of Plasmodium falciparum in an area of seasonal malaria transmission. AB - A longitudinal study of cellular and serological responses to the major merozoite surface protein of Plasmodium falciparum (PfMSP1) has been conducted in a malaria immune population living in The Gambia, where malaria transmission is seasonally endemic. Recombinant or native proteins representing the sequence of PfMSP1 from the Wellcome strain of P. falciparum were used in in vitro lymphocyte proliferation, cytokine and antibody assays. Cellular responses of individual donors fluctuated over time, independent of seasonal changes in malaria transmission whereas anti-PfMSP1 antibody levels were remarkably stable. At a population level, IFN gamma responses were both more prevalent and of greater magnitude at the end of the rainy (malaria transmission) season than during the dry season. Responses of individuals living in a rural village were compared with those of individuals living in an urban area with much lower levels of malaria transmission. Malaria infections were more likely to be symptomatic in urban dwellers than in inhabitants of rural villages but no significant differences in the level or prevalence of cellular or serological responses were seen between the two groups. However, urban dwellers with current symptomatic malaria infections had somewhat lower anti-PfMSP1 antibody levels than their healthy, non parasitaemic neighbours. PMID- 7877850 TI - The inhibitory effect of ovine recombinant interferon-gamma on intracellular replication of Toxoplasma gondii. AB - A model for the in vitro infection of ovine cells with Toxoplasma gondii tachyzoites has been developed and used to investigate the effect of treatment with ovine recombinant interferon-gamma (ov.rIFN gamma) on parasite replication. Treatment of both alveolar macrophages and fibroblast cells either 24 h pre infection or 2 h post-infection with ov.rIFN gamma inhibited replication of T. gondii and was quantified by suppression of 3H uracil uptake by the parasite. Replication of T. gondii in the fibroblast cells was significantly inhibited by treatment with 200-300 U/ml ov.rIFN gamma, whereas concentrations as low as 1 U/ml suppressed parasite replication in the alveolar macrophages. PMID- 7877851 TI - Trypanosoma cruzi infection in mice enhances the membrane expression of low affinity Fc receptors for IgG and the release of their soluble forms. AB - The membrane expression of low-affinity Fc receptors for IgG (Fc gamma RII/III) on cells and the number of Fc gamma RII/III(+) cells were studied by flow cytometry, using the 2.4G2 MoAb, in mice infected by Trypanosoma cruzi. Cells from spleen, mesenteric lymph nodes and peritoneum were collected on days 10, 20, 30 and 40 post infection (p.i.). The in vivo serum level of soluble Fc gamma RII/III, as well as its in vitro release by cells from infected mice were studied. Parasitaemia and IgG1, IgG2a and IgG2b T. cruzi-specific antibody titres were also recorded. Both the expression of Fc gamma R on cell membrane and the absolute number of Fc gamma R(+) cells increased in spleen and in mesenteric lymph nodes, but not in peritoneum. The modifications in spleen occurred in the early and late parasitaemic phase of infection, i.e., before and after detection of T. cruzi-specific antibodies (from day 10 to 40 p.i.). In mesenteric lymph nodes, the variations were observed only in the early acute infection, when antibodies were not yet detectable at significant levels (on days 10 and 20 p.i.). Higher levels of soluble Fc gamma R were detected in sera and in culture supernatants of spleen and lymph node cells from day 20 to 40 p.i. These results show that T. cruzi infection in mice upregulates the expression and the release of Fc gamma RII/III, in the acute phase of infection, before as well as after the rise of antibody response. PMID- 7877852 TI - Immunosuppression in trypanotolerant N'Dama cattle following Trypanosoma congolense infection. AB - Tsetse-transmitted Trypanosoma congolense infection causes an impairment of in vitro T cell proliferative responses in Boran (Bos indicus) cattle. To assess the importance of this phenomenon as it may relate to the ability of trypanotolerant cattle to control infection with trypanosomes, T cell proliferative responses to mitogenic stimulus with Concanavalin A were measured in N'Dama (Bos taurus) cattle throughout infection. The responses of peripheral blood mononuclear cells from Boran and N'Dama cattle were similar. Depressed proliferative responses were observed with cells of both breeds at 12 days post infection, after which the responses returned to levels similar to those recorded pre-infection. Immunosuppression was also studied in the lymph nodes of a major histocompatibility complex (MHC)-matched pair of N'Dama cattle. Lymph node cells from the infected animal failed to respond to mitogenic stimulus. Co-culture experiments in which the cells from this node were mixed with either lymph node cells or peripheral blood mononuclear cells from the non-infected MHC-compatible animal revealed the presence of suppressor cells, acting in a prostaglandin independent manner, capable of arresting mitogen-induced T cell proliferation. PMID- 7877853 TI - [Diagnosis, treatment and prevention of invasive aspergillosis. A priority target in hospital units]. PMID- 7877854 TI - [Tools, progress and questions in the molecular study of Aspergillus fumigatus and invasive aspergillosis]. AB - Development of A. fumigatus in the host tissues is due to the intrinsic biological characteristics of this fungus and to the impairment of the cellular defence reactions of the host. However, even today the understanding of the factors governing the infectivity of A. fumigatus remains very limited. For example, the cellular mechanisms involved in the killing of A. fumigatus are still not elucidated. The cellular site(s) of infection and the role of the different lung epithelia in the establishment of the fungus are unknown. No specific fungal virulence factors have been identified until now. Molecular biology techniques are powerful tools to investigate the pathogenesis of invasive aspergillosis. Recent developments in the study of this mycosis are presented in this review. PMID- 7877855 TI - [Mechanisms and implications of the adhesion phenomenon in Aspergillus fumigatus]. AB - During the last few years, several works have demonstrated the fixation of different host proteins on Aspergillus fumigatus conidia. Thus, after incubation in the presence of normal human plasma, the C3 component of complement is detected at the surface of conidia. In fact, most of the C3 deposited on conidia is converted in C3b or iC3b which would facilitate their phagocytosis by the macrophages. In the non immune host, the activation of the alternative pathway seems to be the main mechanism of the activation of the complement system by the conidia, but the participation of the classical pathway initiated by the fixation of the C-reactive protein has also been suggested. Aspergillus fumigatus conidia interact also with fibrinogen and laminin. These interactions which are mediated by the D domains of fibrinogen and by the fragment P1 of laminin, are specific. The number of fibrinogen binding sites at the surface of conidia has been calculated to be 1200 by cell, and the dissociation constant 2.2 x 10(-7) M. These interactions could determine the adhesion of conidia to the host tissues as suggested by adherence assays of conidia to proteins immobilized onto wells of microtiter plates. Conidia would bind to the fibrin deposits formed on damaged epithelia in response to the inflammatory reaction, or directly to laminin of the subepithelial basement membrane. Finally, different experiments suggested the identity of the binding sites for C3, fibrinogen and laminin at the surface of A. fumigatus conidia. PMID- 7877856 TI - [Aspergillosis in acquired immunodeficiency syndrome]. AB - From 1983 to 1991 only isolated cases of aspergillosis in AIDS patients were reported; since 1991, an increasing number of cases have been reported suggesting a recent emergence of this fungal infection. Aspergillosis occurs about 10 to 25 months after AIDS diagnosis in patients with CD4 below 50/mm3. Neutropenia and/or steroid therapy, which are known as predisposing factors in aspergillosis, are noticed in about one half of the patients. Previous pulmonary infection, especially pneumocystosis, are very common. Clinical signs are typical of an invasive pulmonary aspergillosis: constant fever, cough, dyspnea, frequent thoracic pains and haemoptysis. Radiologic signs frequently indicate an interstitial infiltration. Nodular and cavitating lesions, pleural effusions, thoracic lymph node enlargement are often present. Diagnosis procedures are realised on bronchoalveolar lavage by direct examination, culture and antigen detection. Aspergillus fumigatus is the most usually species detected. Post mortem diagnosis is frequent. Invasive bronchial aspergillosis, localised infections (aspergilloma, otitis, sinusitis) or disseminated infections (nervous system, heart, kidney, lymph nodes, thyroid) are also described. Prognosis is poor even with treatment (amphotericin B or itraconazole). An earlier diagnosis and treatment of the bronchial colonization could probably improve this prognosis. PMID- 7877857 TI - [Invasive aspergillosis and bone marrow allograft]. AB - Invasive aspergillosis is the most frequent cause of infectious death after allogeneic bone marrow transplantation. Risk factors include the patient's condition (granulocytopenia, immunosuppression) and his environment (air spores count). Pulmonary infections are prominent. Other infections usually occur in the setting of disseminated disease via hematogenous spread. Cerebral aspergillosis appears to be especially frequent and of very poor prognosis. Infections of the paranasal sinuses occur less often and are associated or not with pneumonitis. Mycologically confirmed diagnosis is difficult to obtain: treatment will often have to be instored on clinical findings alone or even on an empiric basis. However, the prognosis remains extremely poor explaining the actual physicians' concern in finding a better prophylaxis of this infection. PMID- 7877858 TI - [Aspergillosis and malignant hemopathies]. AB - Infections caused by fungi of the genus Aspergillus have become a major and dangerous problem in the modern treatments of blood diseases using cytotoxic drugs. Invasive pulmonary aspergillosis is the usual clinical manifestation of the disease. The clinical signs, not very suggestive, are those of an infective pneumonia and localized radiological forms are initially more frequent in most cases. The extra pulmonary forms are frequent: nose and sinus, skin, bone, digestive, central nervous system are principal localisations; but all organs may be affected by the processus of dissemination. The proximal tracheobronchial localisations may be seen by fibroscopy in 20% of cases, associated to invasive pulmonary aspergillosis. Diagnosis rests on pathological data, but in many cases the only possible examinations are broncho-alveolar lavage and bronchial brushing. The positive results are a major test of diagnosis. PMID- 7877859 TI - [Aspergillosis and renal, heart and lung transplantation]. AB - The increase of organ transplantations during the last decades conjointly with the prescription of heavy immunosuppressive drugs, has led to an increased incidence of new invasive aspergillosis (IA). This study is a report of the Broussais Hospital experience from 1968 to 1993 on kidney, heart and heart and lungs transplantations. It concerns 21 IA cases. Incidence was 0.5% for kidney, 4.5% for heart and 18% for heart and lungs transplantations. The most important risk factors were the increase of immunosuppressive therapy (66% of the cases), neutropenia (19%), and renovation of the hospital wards (36%). Lung was the most frequent site of infection (95% of the cases), clinical symptoms were no significant. Diagnosis procedures were realised on biopsy (23%) and on bronchoalveolar lavage (66%). Usual amphotericin B treatment was disappointing: mortality rate of 77%, the liposomal preparation of the drug seemed to be more efficient: mortality rate of 50%. Itraconazole appeared to be used in succession with a careful adaptation of posology. Prophylactic amphotericin B in a local way (sprays and aerosols) led to a good efficiency jointly with the patient isolation during constructions in the hospital area. PMID- 7877860 TI - [Radiological aspects of invasive aspergillosis]. AB - Invasive aspergillosis is a life-threatening illness, whose diagnosis is difficult: clinical signs are indeed not specific, and biological and mycological exams are not always conclusive. Radiological exams are essential for the diagnosis of this disease allowing to start an early intensive appropriate therapy. According to the literature and to their own experience the authors report the main radiological patterns with emphasis on the pulmonary and cerebral affections. PMID- 7877861 TI - [Invasive aspergillosis: management of mycological diagnosis]. AB - Establishing the diagnosis of invasive aspergillosis consists primarily in the detection of Aspergillus hyphae, the invading form of the fungus, mainly from respiratory tract specimens and by cultural isolation. In this overview of the topic, we emphasise the major obstacles to the successful diagnosis of this fungal infection. The authors describe then the general procedures for histopathological and mycological diagnosis (samples, choice of method and the interpretation of results). Finally, they summarise, from literature the success rate in detecting Aspergillus, depending on the potentially infected sites and the specimens examined (broncho-pulmonary or extra-pulmonary). PMID- 7877862 TI - [Specific antigens and antibodies in invasive aspergillosis]. AB - Early diagnosis of invasive aspergillosis is of utmost importance but difficult to achieve. Serological methods were developed mainly because all the other diagnostic approaches had major drawbacks. The detection of antibodies against Aspergillus antigens provided little interesting information, since anti Aspergillus antibodies were commonly found in healthy people, while, on the other hand, immunocompromised patients often failed to raise antibodies. Several groups of investigators showed that the detection in serum or urine by RIA or ELISA of Aspergillus antigens, was a highly specific indication of invasive disease. The sensitivities of the techniques, however, were moderate, partially due to the low antigen concentrations and the transient character of antigenemia. The only commercially available test is a latex agglutination test detecting 15 ng/ml galactomannan. It has a high specificity but reported sensitivities varied between 42% and 94.7%. Results with an experimental double-sandwich ELISA detecting about 1 ng/ml galactomannan suggest that the improvement of detection limit also greatly increases the clinical value of the test: patients become and remain positive 2 to 10 weeks earlier. If these results are confirmed, antigen detection could become a essential element in the management of an immunocompromised patient population. PMID- 7877863 TI - [Curative treatment of invasive aspergillosis]. AB - Invasive aspergillosis is an opportunist infection in immunosuppressed hosts among the most difficult to diagnose and to treat. A wide variety of clinical forms exist which may not require the same treatment for each of them. Intravenous amphotericin B and itraconazole are the only available antifungal agents. Amphotericin B is often considered as the gold standard treatment despite its high toxicity particularly with high dosage (1-1.5 mg/kg/day) and its poor results namely in bone marrow transplant recipients. Lipidic amphotericin B is less toxic allowing administration of higher dose however relevant data are limited. Itraconazole is an excellent anti Aspergillus antifungal with low toxicity, however there is a wide intersubject variation in intestinal absorption. It may represent a valuable alternative to amphotericin B in case of intolerance or as a relay treatment and possibly in some cases as a first choice treatment. More studies are necessary particularly in granulopenic patients. Comparative study are urgently needed between both drugs and with new molecules to indicate the best treatment according to the clinical form. The use of hematopoietic growth factors and surgery may improve the outcome. PMID- 7877864 TI - [Role of chemoprophylaxis in the prevention of invasive aspergillosis]. AB - Invasive aspergillosis remains a severe infection, and the mortality is high, specially in some patients such as bone marrow transplants. Prophylaxis may be considered either in patients without previous aspergillosis, or in patients cured from previous aspergillosis and exposed again to immunosuppression. The efficacy of prophylaxis may be difficult to demonstrate, due to the relatively low incidence of aspergillosis and the possible lack of proven mycologic diagnosis. The different possibilities of prophylaxis (systemic antifungal treatment, local therapy) will be discussed. PMID- 7877865 TI - [Drug perspectives in the treatment of invasive aspergillosis]. AB - The frequency of infections caused by Aspergillus sp. is on the rise, and the mortality is high in the disseminated forms of the disease. Amphotericin B is theoretically the gold standard treatment, but remains inefficient in severely immunocompromised patients, particularly bone-marrow transplants. The interest of lipidic formulations of amphotericin B, triazoles, new antifungal drugs targeted on the fungal cell wall and immunomodulators is discussed. PMID- 7877866 TI - [Links between risks of aspergillosis and environmental contamination. Review of the literature]. AB - An increasing number of nosocomial invasive aspergilloses is related with the development of new therapies and to Aspergillus spores in the vicinity of the patient. The infiltration of thermophilic fungal spores in the patients' environment is linked not only with contaminated air systems but also to different other factors among which earth moving, demolition or renovation works adjacent to or inside the hospital. Potted plants and individual sachets of ground pepper distributed to patients are another source of Aspergillus spores. To limit fungal exposure, patients undergoing bone marrow transplant should be isolated under laminar flow while simple procedures such as taping windows and doors, shutting down air systems and mycological environmental control measures should be encouraged to protect immunocompromised patients. PMID- 7877867 TI - [Evaluation and validation of controls of aerobiocontamination in the prevention of nosocomial invasive aspergillosis]. AB - Further to an invasive epidemic pulmonary aspergillosis, occurred in an onco hematologic pediatric unit, an emergency plan has been organised and prophylactic precautions has been taken. The authors have retrospectively analysed the results concerning the aerial contamination. The authors have evaluated the efficacy of these prophylactic precautions. Their good results allow them to validate cleaning, disinfection and surveillance protocols. PMID- 7877868 TI - [Contamination by aspergillosis: evaluation of preventive measures and monitoring of the environment]. AB - Aspergillosis has become a major fungal infection in hospitals since the advent of immunosuppressive therapy in the last fifteen years. Aspergilli are saprophytic and ubiquitous fungi and are associated with pulmonary and disseminated infections in immunodepressed patients with a mortality rate of about 85%. Aspergillosis is an air-borne infection, thus intensive care units should be conceived so as to decrease the outer risk of contamination. In the first part of this chapter the conception of such a unit is presented, taking the bone marrow transplantation unit of St-Louis Hospital as an example. A prospective study of the quality of the environment is a complementary and necessary information. In the second part of this chapter, the methods of airborn control of Aspergillus sp. are investigated. According to the literature, commun concepts can be drawn to evaluate nosocomial risks of aspergillosis. Nevertheless in the absence of a defined and accepted methodology, it is not possible up to that date to propose norms and acceptable norms of levels of contamination adapted to the degree of immunodepression of patients. PMID- 7877869 TI - [Integrated struggle against aspergillosis at the level of a single hospital or a hospital cluster]. AB - Invasive nosocomial aspergillosis (INA) has become an increasing public health problem in hospitals whose inpatients are severely immunocompromised, i.e. in case of aplasia, bone marrow or organ transplants. The hospital's responsibility is engaged, all the more so since numerous INA cases have been reported during hospital construction work. Prevention measures must be implemented at the time of high risk activities (bone marrow graft, transplantation) or as soon as predisposed patients (aplastic) are admitted in hospitals. In case of hospital construction work, those measures must be adapted to the type of work and to the localization of the exposed patients. The first step of an integrated control strategy is to identify the aspergillus risk units in the hospital according to the immunocompromised state of their patients. The second step consists in the implementation, for those units, of effective protection measures concerning the control of hospital contamination sources, the patient's food, the architecture, the air treatment facilities, the staff organization and training. The third step is to apply a triple surveillance: epidemiological for the disease, technical for the air treatment facilities, mycological for the patients environment. In case of construction work, in or near the hospital, an evaluation of the Aspergillus risk level according to the construction work plan must be undertaken for each high risk unit. This risk level conditions the specific measures which have to be implemented. In the network of epidemiological INA surveillance of the Assistance Publique hospitals in Paris, those measures have been published as a recommendation guide. PMID- 7877870 TI - Molecular analysis of the hematopoietic microenvironment. PMID- 7877871 TI - Expression of multiple gap junction proteins in human fetal and infant hearts. AB - Mammalian cardiac myocytes express multiple gap junction channel proteins or connexins. Expression patterns of the avian homologues of the mammalian cardiac connexins change during cardiac morphogenesis in association with changes in the electrophysiologic properties of intercellular junctions in chick cardiac myocytes. To determine whether expression of cardiac connexins is developmentally regulated in humans, we characterized connexin mRNA and protein content and distribution in hearts of 11 human fetuses (74 to 122 d gestational age), seven children (0.5 mo to 3 y of age), and two adults. Northern blot analysis identified transcripts of connexin40 (Cx40), connexin43 (Cx43), and connexin45 (Cx45) genes in all hearts analyzed. Cx40 mRNA was approximately 5-fold more abundant in samples from fetal hearts than in hearts of children or adults. However, fetal samples used for RNA extraction included atrial as well as ventricular myocardium, whereas samples from children and adults were exclusively ventricular. Northern analysis of adult human right atrial appendages revealed abundant Cx40 mRNA, thus suggesting that the greater amount of Cx40 signal seen on Northern blots from fetal hearts could have been attributable to atrial contributions. Neither Cx43 nor Cx45 mRNA varied significantly in amount in samples from the different developmental stages analyzed. Immunofluorescence identified abundant Cx43 in the known distribution of gap junctions in myocytes in sections of all hearts. Cx45 staining was inconspicuous in fetal hearts but was readily apparent in cardiac myocytes in hearts of older subjects. In contrast, Cx40 staining in the ventricle was confined to mural coronary arteries, apparently in endothelial cells, whereas in the atrium Cx40 staining at myocyte junctions was abundant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877872 TI - Search for highly conserved viral and bacterial nucleic acid sequences corresponding to an etiologic agent of Kawasaki disease. AB - The use of conventional methods to detect a possible infectious cause of Kawasaki disease (KD) has been unsuccessful. Using the polymerase chain reaction and DNA hybridization techniques, we have sought evidence that a known or new herpesvirus, parvovirus, or bacterial pathogen is related etiologically to KD. Peripheral blood DNA from acute KD patients was subjected to amplification and dot-blot hybridization to detect the presence of herpesvirus DNA, and acute KD peripheral blood and serum DNA were subjected to dot-blot hybridization for the presence of parvoviral DNA. All samples were negative for both herpesvirus and parvovirus DNA. In addition, we analyzed buffy-coat white blood cell DNA, synovial fluid DNA, and frozen autopsy and formalin-fixed, paraffin-embedded myocardial tissue DNA from KD patients for the presence of highly conserved bacterial 16S ribosomal RNA gene sequences with the polymerase chain reaction, and all were negative. These results argue against a direct pathogenic role for herpesviruses, parvoviruses, and bacteria in KD. This approach to the detection of highly conserved genomic sequences among broad groups of microorganisms can be adapted for the detection of other groups of microorganisms and may yet prove useful in the search for an etiologic agent of KD. PMID- 7877873 TI - Renal function in preterm neonates. AB - The plasma creatinine concentration is elevated at birth and decreases concomitantly with the rapid increase in glomerular filtration rate that occurs in the first postnatal weeks. The velocity of these changes was assessed during the first 3 wk of life of 66 term and preterm infants. The plasma creatinine concentration, creatinine clearance, and sodium fractional excretion were measured serially at weekly intervals, starting 1-4 d after birth [mean = 1.5 +/- 0.8 (SD) d]. Premature infants were separated into three groups according to their birth weight: group 1, 1001 to 1500 g; group 2, 1501 to 2000 g; and group 3, 2001 to 2500 g. Group 4 included 28 term infants (mean birth weight = 3165 +/- 78 g). Mean gestational ages in the preterm groups were 31.3, 32.8, and 34.4 wk in groups 1, 2, and 3, respectively. The plasma creatinine concentration on d 1.5 was significantly higher in preterm (91 +/- 4 mumol/L) compared with term infants (66 +/- 3 mumol/L). The differences in plasma creatinine were still present during the second week of life, with values of 64 +/- 5, 58 +/- 7, 47 +/- 8, and 40 +/- 4 mumol/L in groups 1, 2, 3, and 4, respectively. The difference vanished by d 22-23. On d 1.5, creatinine clearance correlated positively with gestational age, amounting to 0.65 +/- 0.14, 0.92 +/- 0.19, 1.42 +/- 0.31, and 3.36 +/- 0.32 mL/min in groups 1, 2, 3, and 4, respectively. Creatinine clearance increased rapidly with postnatal age, the velocity of the maturation being less marked in the most premature infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877874 TI - Effects of prenatal exposure to betamethasone and indomethacin on the glomerular filtration rate in the preterm infant. AB - The effects of gestational age (GA), body weight, and prenatal exposure to betamethasone and indomethacin on the glomerular filtration rate (GFR) on d 3 of life in preterm infants were studied. GFR measurements were performed in 147 preterm infants with a GA between 23.4 and 37.0 wk by means of the continuous inulin infusion technique. Mean GFR values increased significantly with GA (r = 0.60, p < 0.001) and with body weight (r = 0.44, p < 0.001). Multivariate analysis indicated that GA was the most important determinant for this increase. Prenatal exposure to indomethacin resulted in significantly lower GFR values ( 0.15 +/- 0.03 mL/min, p < 0.001) at d 3 after birth. Prenatal administration of betamethasone and indomethacin significantly (p < 0.001) increased the GFR in comparison with exposure to indomethacin alone to levels not different than those seen in patients who were not prenatally exposed to betamethasone or indomethacin. GFR measurements were repeated in 40 preterm infants on d 10 after birth. During this 7-d period, a significant increase in GFR values (0.17 +/- 0.03 mL/min, p < 0.001) was detected. This postnatal increase in GFR values was independent of GA and was not influenced by prenatal exposure to betamethasone or indomethacin. We conclude that prenatal exposure to betamethasone or indomethacin exerts significant effects on the renal function of preterm infants in the first days of life. PMID- 7877875 TI - Rate-dependent distal renal tubular acidosis and carnitine palmitoyltransferase I deficiency. AB - An infant girl presented with recurrent episodes of Reye-like syndrome associated with hypoketosis and plasma carnitine levels in the high-normal range. A liver biopsy revealed massive macrovesicular steatosis. Ketogenesis was absent after a long-chain triglyceride loading test; in contrast, the medium-chain triglyceride loading test resulted in a brisk rise in plasma ketone concentration. Carnitine palmitoyltransferase I deficiency was demonstrated in cultured skin fibroblasts. Hypoglycemia was only found once in the neonatal period. Renal carnitine handling was normal except for a higher renal threshold for free carnitine. Mild, persistent metabolic acidosis was a constant feature, even during periods between metabolic decompensation. Evaluation of the renal acidification capacity showed a failure to acidify the urine during spontaneous acidosis but increased acid excretion and a normal decrease of urinary pH after acid loading. Also, a small difference between urine and blood PCO2 was found after bicarbonate administration. This acidification defect can best be explained as an abnormality in distal tubular H+ secretion: a rate-dependent distal tubular acidosis.off is speculated that long-chain acylcarnitines, substances that cannot be formed by carnitine palmitoyltransferase I-deficient patients, play an essential role in renal acid-base homeostasis. PMID- 7877876 TI - Subarachnoid hematoma attenuates vasodilation and potentiates vasoconstriction induced by vasoactive agents in newborn pigs. AB - The effects of perivascular blood on pial arteriolar vasoreactivity to selected vasodilators and vasoconstrictors were examined in vivo in a newborn pig model. alpha-Chloralose-anesthetized newborn pigs were fitted with closed cranial windows 4 d after cortical subarachnoid injections of autologous blood. The responsiveness of pial arterioles to topical application of dilator agents [iloprost, prostaglandin E2 (PGE2), histamine, and sodium nitroprusside (SNP)] and vasoconstrictor agents [leukotriene C4 and endothelin-1 (ET-1) in artificial cerebrospinal fluid was studied in control and blood-injected piglets. Pial arterioles dilated dose dependently in response to topical application of iloprost, PGE2, histamine, and SNP in the control group, with increases in diameter of 54, 44, 67, and 50% at 10(-8) M, 10(-5) M, 10(-5) M, and 10(-5) M, respectively. These dilations in response to iloprost, PGE2, and histamine in the blood-injected piglets were significantly attenuated to 23, 18, and 34%, respectively, whereas the dilation in response to SNP was not changed (64%). Constrictions in response to 10(-8) M leukotriene C4 and ET-1 were 16 and 26% and were potentiated by hematoma to 36 and 43%, respectively. The lowest dose of ET-1 (10(-12) M) significantly dilated pial arterioles in the control but not in the blood-treated group. We conclude that prolonged exposure of pial arterioles to perivascular blood attenuates cerebrovascular dilation in response to selected vasoactive agents (iloprost, PGE2, and histamine) but not to SNP, suggesting that blood-induced attenuation of vasodilation and the generalized vasoconstriction may involve inhibiting the prostanoid/cAMP signaling pathway.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877877 TI - Effects of surgery and asphyxia on levels of nucleosides, purine bases, and lactate in cerebrospinal fluid of fetal lambs. AB - During severe oxygen shortage, the fetal brain resorts to anaerobic metabolism and ATP becomes catabolized. High levels of nucleosides, hypoxanthine, and xanthine (ATP catabolites) in cerebrospinal fluid (CSF) may therefore be associated with increased neonatal neurologic morbidity. In 22 fetal lambs (3 to 5 d after surgery, gestational age 123.5 +/- 3.5 d), arterial oxygen content was progressively reduced to 35% of the baseline value with a balloon occluder around the maternal common internal iliac artery. This resulted in a 1-h period of asphyxia, leading to a pH of 7.02 +/- 0.03 and a base excess of -17.0 +/- 1.0 mM. Mortality was 50%. CSF was sampled from the spinal cistern and analyzed using HPLC. During reoxygenation, hypoxanthine and xanthine may serve as substrate for xanthine oxidase with concomitant production of oxygen-derived free radicals, which may aggravate cerebral damage. The main difference between surviving and nonsurviving animals was the speed of increment of ATP catabolites in CSF: in the surviving group levels increased steadily, recovery values being significantly elevated compared with asphyxia values, whereas in the nonsurviving group the rise was rapid and levels during asphyxia did not differ significantly from levels during recovery. We conclude that 1) catheterization of the spinal cistern leads to increased levels of CSF hypoxanthine, xanthine, and inosine, and 2) during fetal asphyxia, levels of these ATP catabolites and lactate in CSF increase. 3) Maximum levels are reached during the recovery period and are similar for surviving and nonsurviving animals, but during asphyxia CSF levels of hypoxanthine and lactate were higher in the nonsurviving fetuses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877878 TI - Simultaneous measurements of cerebral circulation with electromagnetic flowmetry and Doppler ultrasound velocity in the newborn pig. AB - Cerebral blood flow measurement has been an important investigative tool in newborns at risk for perinatal brain damage. The validity of Doppler cerebral blood flow velocity measurements depends on a constant vessel diameter. We have validated Doppler against the electromagnetic flowmeter (EM) using a modified common carotid artery model in the 1-d-old piglet. Two sets of continuous and simultaneous recordings were performed: 1) the Doppler and EM probe on the same common carotid artery (extracerebral branches were ligated), and 2) the EM probe on the common carotid artery and the Doppler probe recording from an intracerebral artery through an artificial fontanel. Arterial partial pressure of carbon dioxide (PaCO2) was manipulated (2.8-7.4 kPa), as was arterial blood pressure (3.7-9.3 kPa). Simultaneous EM flow and estimated Doppler flow were compared. Ninety-three recordings were obtained with both transducers on the modified carotid artery, and 49 were obtained with the Doppler insonicating an intracerebral artery. A multiple regression model was used for statistical analysis. The correlation between EM and both sets of Doppler measurements for individual animals was > 0.95 and was unaffected by changes in arterial blood pressure or PaCO2. Thus, the common carotid and the intracerebral artery investigated did not change their diameter significantly in response to PaCO2 or arterial blood pressure. The relationships between EM and Doppler in the individual animal were all linear but revealed great variability in the slopes due to the unknown vessel diameter and angle of insonication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877879 TI - Infantile onset spinocerebellar ataxia represents an allelic disease distinct from other hereditary ataxias. AB - Hereditary ataxias are a heterogeneous group of progressive neurodegenerative disorders characterized by symptoms and signs originating mainly in the CNS. A new representative of this disease group is infantile onset spinocerebellar ataxia, an autosomal recessively inherited syndrome so far reported only in the genetically isolated Finnish population. The etiology of hereditary ataxias still remains unknown, but the gene loci behind many of them have been mapped to different chromosomal regions. We have carried out linkage analyses with markers on the regions of the previously identified ataxia loci to determine whether the infantile onset spinocerebellar ataxia syndrome represents the same allelic disease as any of the previously identified hereditary ataxias. Here we report that the infantile onset spinocerebellar ataxias syndrome does not segregate with any of the markers closely linked to the other hereditary ataxias. Consequently, it represents a genetically distinct disease, the gene locus of which still has to be identified. PMID- 7877880 TI - Uridine diphosphate hexoses in leukocytes and fibroblasts of classic galactosemics and patients with other metabolic diseases. AB - To examine uridine diphosphate hexose (UDPhexose) content of cells that have more complete metabolic patterns than erythrocytes, which have been commonly used in the study of galactosemia, the concentrations of uridine diphosphate galactose (UDPgalactose) and uridine diphosphate glucose (UDPglucose) were determined in white blood cells (WBC) and fibroblasts cultured from skin biopsies. Leukocyte UDPgalactose and UDPglucose values were determined in 60 normal individuals, 14 classic galactosemics, and 18 patients with other metabolic diseases on protein restricted and low-lactose diets. There was no difference in the average concentration of these compounds between any of these groups. There was no relationship between age and WBC UDPhexose content or correlation of WBC and erythrocyte UDPhexose levels in the same blood specimens. WBC from galactosemic individuals differ from their red blood cells because the former do not show the low average UDPgalactose levels and abnormal UDPglucose to UDPgalactose ratio previously reported for erythrocytes from galactose-1-phosphate uridyltransferase deficient individuals. Fibroblast cell lines from 10 normal and 10 galactosemic individuals, cultured and grown to confluence in glucose medium, also showed no difference in nucleotide sugar concentrations. Thus far, of the cell types easily available, red blood cells appear to be unique in showing an abnormality in nucleotide sugar metabolism. The fact that galactosemic fibroblasts demonstrate no abnormality in the concentration of these compounds suggests that the defective galactosylation that has been observed in galactosemic fibroblasts is not due to unavailability of UDPgalactose. PMID- 7877881 TI - Superoxide anion release by polymorphonuclear leukocytes in whole blood of newborns and mothers during the peripartal period. AB - Superoxide anion (.O2-) production was investigated in whole blood of mothers in the peripartal period and in neonates. Blood samples from 14 mothers undergoing vaginal delivery (VD) were tested at the beginning of labor, during labor, after delivery, and 4 d after delivery. Nine mothers undergoing elective cesarean section (ECS) were tested before anesthesia, after extraction of the fetus, and 4 d later. Seventy-two healthy, full-term newborn infants were examined at birth and on the fourth day of life. Red cell glutathione peroxidase, catalase, glutathione reductase, and superoxide dismutase activities were also measured at birth and on the fourth day of life in 26 of the 72 neonates. Higher .O2- levels were detected in mothers undergoing VD compared with ECS (p < 0.05). A significant decrease was detected in zymosan-stimulated .O2- production between cord and fourth-day blood samples in both VD- and ECS-delivered infants (p < 0.01). Zymosan-stimulated samples showed higher values after VD than ECS, both in cord blood (p < 0.004) and on the fourth day of life (p < 0.006). A positive correlation was found between .O2- release in zymosan-stimulated cord blood and that found in the mothers at the beginning of labor (r = 0.654; p < 0.01), during labor (r = 0.721; p = 0.008), and after delivery (r = 0.832; p = 0.0008). A positive correlation was also found between .O2- release and glutathione peroxidase on the fourth day (r = 0.709, p = 0.014).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877882 TI - The effects of recombinant human granulocyte-macrophage colony stimulating factor on the neutrophil respiratory burst in the term and preterm infant when studied in whole blood. AB - To investigate further the susceptibility to infection of newborn infants, particularly those born prematurely, we have used a "whole blood" flow cytometric assay to compare the respiratory burst activity in recombinant human granulocyte macrophage colony stimulating factor "primed" neutrophils obtained from healthy adults, term infants, and preterm newborn infants. The use of whole blood avoids prior cell separation procedures that may cause artifactual activation or priming. In healthy adults (n = 21), the bacterial cell wall peptide N-formyl methionyl-leucyl-phenylalanine induced little neutrophil respiratory burst activity, suggesting that the circulating cell is relatively quiescent. Prior exposure to recombinant human granulocyte-macrophage colony stimulating factor augmented the median N-formyl-methionyl-leucyl-phenylalanine response by 425%. In cord blood from full-term neonates (n = 9), recombinant human granulocyte macrophage colony stimulating factor produced less enhancement of the N-formyl methionyl-leucyl-phenylalanine response (345%), but the absolute level of respiratory burst activity was at least as great as in adults, suggesting that the neutrophils are fully functional and partially primed after delivery. In preterm infants receiving intensive care (n = 10), the degree of priming was similar to that in neutrophils from term infants (344%), although the absolute level of respiratory burst activity was reduced (p = 0.0003). In response to stimulation with phorbol ester, 73.5% (18-99%) (median and range) of neutrophils obtained from adults and 77.6% (50-92%) from term babies exhibit respiratory burst activity detectable in the whole blood assay. However, in neutrophils obtained from preterm infants, there was a significant reduction in the phorbol ester-induced respiratory burst, with only 32.9% (21-61%) of cells responding (p = 0.0129). PMID- 7877883 TI - Altered leukotriene generation in leukocytes from cystinotic children. AB - Upon in vitro stimulation with 10 microM ionophore A 23187 for 5 min at 37 degrees C, the generation of leukotriene (LT) C4 in polymorphonuclear leukocytes (PMNL) from nine untreated cystinotic children was significantly increased compared with that in eight control children (p < 0.01) and 25 normal adults (p < 0.001) (417.4 +/- 70.0 versus 177.0 +/- 30.9 and 164.9 +/- 19.5 pmol/l x 10(7) cells, respectively). Concomitantly with the increased generation of LTC4, LTB4 production in PMNL from untreated cystinotic children was decreased compared with controls, whereas the total amount of LTA4 derivatives was similar in the three groups. The increase in LTC4 production was not related to the number of eosinophils present in the PMNL preparations from cystinotic children, which was similar to that of control subjects. PMNL from cystinotic children treated with cysteamine, an aminothiol compound that decreases the intracellular cystine content, generated smaller amounts of LTC4 upon ionophore A 23187 stimulation than PMNL from untreated cystinotic children. In addition, abrogation of the cysteamine treatment for 3 or 4 d led to an increase in LTC4 production. These findings suggest that the metabolic abnormalities taking place in infantile cystinosis may favor the biosynthesis of LTC4 from PMNL. PMID- 7877884 TI - Reactivity of gliadin and lectins with celiac intestinal mucosa. AB - The binding patterns of gliadin and selected lectins to jejunal biopsy specimens obtained from children with total villous atrophy during active celiac disease (CD; 19 patients) and in remission (16 patients) were examined by light microscopy. Three categories of carbohydrate-specific lectins were chosen for the study: those recognizing mannose/glucose residues, those recognizing N-acetyl glucosamine/glucose (glcNAc/glc) residues, and those recognizing N acetylgalactosamine/galactose (galNAc/gal) residues. The galNAc/gal lectins, with the exception of phaseolus vulgaris agglutinin variants, presented a typical staining of the luminal surface of the jejunal mucosa obtained from CD patients. However, these lectins displayed no reactivity to jejunal sections of CD patients in remission or control biopsies that included healthy children (25 children) and patients suffering from cow milk protein allergy (10 children). The glcNAc/glc lectin showed a strong preferential recognition of CD jejunal tissue but also bound with less intensity to specimens from patients with cow milk allergies and healthy children. Unlike other galNAc/gal lectins, phaseolus vulgaris agglutinin variants were indistinguishable in their binding patterns to the mucosa of control groups and CD patients in remission and failed to react to CD biopsies. The mannose/glc lectins were not distinctive in their binding patterns. In all cases, lectin binding was specifically inhibited by the lectins' competitive saccharides. Atypical of lectin binding patterns, gliadin reactivity was restricted to intracellular areas of enterocytes and was unique to active CD mucosa. The distinctive binding patterns of lectins and gliadin provide a diagnostic tool to distinguish patients with active CD from those in remission or patients with other intestinal disorders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877886 TI - Activation of the plasma clotting, fibrinolytic, and kinin-kallikrein system in preterm infants with severe idiopathic respiratory distress syndrome. AB - We studied the activation pattern of clotting, fibrinolysis, and kinin-kallikrein during the first 5 d of life in 10 preterm infants with signs of severe idiopathic respiratory distress syndrome (IRDS) after birth (IRDS group) and in 12 healthy preterm infants (reference group). We found systemic activation of clotting, fibrinolysis, and kinin-kallikrein in the IRDS infants within 12 to 24 h of birth, represented by increased median thrombin-antithrombin III complex formation (90 ng/mL versus 10 ng/mL in the reference group, p < 0.05), increased mean tissue-type plasminogen activator plasma concentrations (11.8 ng/mL versus 3.5 ng/mL in the reference group, p < 0.05), and increased mean plasma kallikrein activity (182.6% versus 162.0% of maximal activated human plasma in the reference group, p < 0.05), respectively. Clotting activation was accompanied by a significant decrease of the platelet count. Clotting and fibrinolytic activity decreased in the IRDS group during the first 2 to 3 d of life. Kinin-kallikrein activation was accompanied by decreased plasma kallikrein inhibitor activity values and did not change throughout the study period. Plasma factor XII activity was not significantly increased in the IRDS infants during the first 2 d of life but did significantly increase thereafter. The cause of simultaneous activation of clotting, fibrinolysis, and kinin-kallikrein in our IRDS infants has not yet been clarified. However, this activation process may contribute to lung injury such as that described in the adult respiratory distress syndrome. PMID- 7877885 TI - Developmental changes in gastric fundus smooth muscle contractility and involvement of extracellular calcium in fetal and adult guinea pigs. AB - Delayed gastric emptying is a common problem in preterm infants. The factors underlying this gastroparesis remain unsettled but may involve immaturity of smooth muscle contraction. The present study was designed to test this hypothesis. Muscle strips from the gastric fundus of fetal and adult guinea pigs were studied in vitro for their contractile response to receptor activation (acetylcholine and bethanechol) and membrane depolarization (potassium chloride). The dose-response curves were analyzed for differences in active force development (kg/cm2). The role of extracellular calcium (Ca2+) in the contractile responses was determined by contracting the tissues in a zero-Ca2+ physiologic saline solution and in the presence of nifedipine, a voltage-dependent Ca2+ channel blocker. The results demonstrate the following: 1) tissues from adult animals developed significantly more active force when tested with acetylcholine, bethanechol, and potassium chloride; 2) tissues from the fetal animals were relatively unresponsive to contraction with potassium chloride compared with the adult; and 3) both nifedipine and incubation in a zero-Ca2+ physiologic saline solution had a significantly greater inhibitory effect on the contractions of adult than fetal muscle strips. Our data indicate that smooth muscle in the gastric fundus develops increasing force with maturation. The increased contractility in the adult fundus appears to be due to an increased involvement of extracellular calcium influx, in part through voltage-dependent Ca2+ channels. PMID- 7877887 TI - Isolated growth hormone deficiency type IA associated with a 45-kilobase gene deletion within the human growth hormone gene cluster in an Italian family. AB - An Italian family with three children presenting with isolated growth hormone (GH) deficiency type IA is described. Restriction endonuclease analysis revealed that the cause of hGH deficiency was a 45-kb gene deletion within the hGH chorionic somatomammotropin (CS) gene cluster, encompassing the GH-1, CS-L, CS-A, and GH-2 genes. DNA sequence analysis and polymerase chain reaction amplification between two sequences located on each side of the deletion breakpoint accurately identified the deletion breakpoints and indicated that the regulatory sequences located upstream from the TATA box of the mutant CS-B belong to the GH-2 gene. Two of the affected children developed high-titer anti-hGH antibodies after recombinant hGH treatment with secondary growth arrest, whereas the third one maintained normal growth in the presence of very low-titer antibodies. This is the first report of a large deletional mutation within the hGH-CS gene cluster accompanied by phenotypic heterogeneity in terms of growth response and antibody formation in the different patients. PMID- 7877888 TI - Evidence of a steroidogenic enzyme gene dose effect on adrenal gene expression in hereditary rabbit congenital adrenal hyperplasia. AB - We previously reported the gene deletion encoding cytochrome P-450 cholesterol side-chain cleavage enzyme (P-450SCC, resulting in complete elimination of the adrenal gene expression and causing congenital adrenal hyperplasia in the rabbit. Using the rabbit congenital adrenal hyperplasia model, we investigated the wild type (wt) P-450SCC gene dose effect on gene expression in three P-450SCC genotype animals [wt/wt, wt/mutant (mt), mt/mt] identified by Southern blot analysis. Northern blots using a rabbit P-450SCC cDNA probe revealed no detectable P-450SCC mRNA in individual adrenals of animals with congenital adrenal hyperplasia (mt/mt) and approximately half or slightly less than half the levels of the mRNA in the pooled adrenals of five heterozygous (wt/mt) newborn animals compared with the mRNA levels in the pooled adrenals of five homozygous normal (wt/wt) newborn animals. Identical P-450SCC mRNA levels were found individual adrenals of adult animals with regard to the P-450SCC genotype, although at a higher expression level than in the newborn animals of the same genotype. Control Northern blots using human CPY21-B cDNA and cytoplasmic actin cDNA probes confirmed the accuracy and integrity of RNA. Western immunoblotting using anti-ovine P-450SCC antibody revealed decreased P-450SCC protein in the adrenals of wt/mt animals at approximately half the level of the P-450SCC protein in the adrenals of the wt/wt animals. Baseline and ACTH-stimulated serum corticosterone (B) levels in vivo were similar between the age-matched wt/mt and wt/wt animals, whereas ACTH stimulated B levels in adult animals were higher than those in the newborn animals irrespective of P-450SCC genotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877890 TI - Diet is important in assessing lung cancer risk factors in nonsmokers. PMID- 7877889 TI - Insulin responses to intravenous glucose and the hyperglycemic clamp in cystic fibrosis patients with different degrees of glucose tolerance. AB - The relationship between altered insulin secretion and impaired glucose tolerance was studied in 32 cystic fibrosis patients, 16 men and 16 women, aged 8-26 y, using oral and i.v. glucose tolerance tests and a hyperglycemic glucose clamp (10 mmol/L). Seven of these subjects were already being treated with insulin; seven had fasting blood glucose levels below 7.2 mmol/L but satisfied diabetic criteria at the oral glucose tolerance test; glucose tolerance was impaired in 13 subjects and normal in five. The insulin responses to the two i.v. glucose stimuli were inversely correlated with the plasma glucose levels (60 and 120 min) and the area under the curve of the oral glucose tolerance test. However, the acute insulin response to i.v. glucose was severely altered in patients with impaired glucose tolerance, whereas plasma insulin levels during the hyperglycemic clamp did not differ from those of healthy subjects. The responses to the two stimuli were dramatically low in the diabetic patients. These results suggest that cystic fibrosis patients with normal or impaired glucose tolerance retain their capacity to secrete insulin. Alterations in the acute phase of glucose-stimulated insulin secretion seem to be principally responsible for the early impairment in glucose tolerance. PMID- 7877891 TI - Importance of supplemental vitamin C in determining serum ascorbic acid in controls from a cervical cancer case-control study: implications for epidemiological studies. AB - Classification of individuals by their vitamin C intake was investigated in 493 control subjects from a cervical cancer case-control study. The influence of dietary and supplemental sources of vitamin C, as well as demographic and life style factors, on serum ascorbic acid were examined. Usual dietary intakes of vitamin C were determined from a food frequency questionnaire and recent intakes from a 24-hour recall taken at the time of blood collection. Vitamin supplement information was obtained at both times. In a regression analysis, the factors found to predict serum ascorbic acid were total recent vitamin C intake, an indicator variable for supplement use, body mass index, number of cigarettes smoked per day, race, education, and age. Higher levels of serum ascorbic acid were found among older nonsmoking highly educated leaner white women. Consideration of supplements, in addition to dietary sources of vitamin C, improved correlation coefficients between serum ascorbic acid and usual vitamin C intake from 0.19 to 0.32 and between serum ascorbic acid and recent intake from 0.36 to 0.56. Furthermore, whereas only a twofold difference between the first and fourth quartiles of serum ascorbic acid was observed using recent dietary vitamin C without supplements, this range increased to sixfold with addition of supplement data. Epidemiological studies should consider use of total vitamin C intakes from supplement and food sources to permit accurate classification of individuals. PMID- 7877892 TI - Effects of retinoids, beta-carotene, and canthaxanthin on UV- and X-ray-induced transformation of C3H10T1/2 cells in vitro. AB - We observed that various retinoids (including all-trans-retinoic acid, 13-cis retinoic acid, and the synthetic retinoid Ro-11-1430) have approximately the same ability to suppress ultraviolet light-induced transformation of C3H10T1/2 cells in vitro. Retinoids also suppress X-ray induced transformation in vitro. Ro-11 1430 has no effect when present for only 1 day after the X-ray exposure but does have a suppressive effect on radiation transformation when present for 5 or 10 days after irradiation. Ro-11-1430 has its major suppressive effect on X-ray transformation when present in irradiated cultures in the confluent stationary phase of growth. Natural beta-carotene (type IV) from carrots, but not synthetic beta-carotene, has the ability to suppress radiation (X-ray)-induced transformation when present for the entire transformation assay period. Natural beta-carotene is without effect on the transformation process when present in irradiated cultures only during confluence. For these retinoids, as well as beta carotene and canthaxanthin, there is a highly significant suppressive effect on radiation transformation and radiation transformation enhanced by 12-O tetradecanoylphorbol-13-acetate when the compounds are present at toxic levels; when nontoxic levels are utilized, these compounds have the ability to suppress the yield of transformed cells to approximately one-half of that observed in irradiated cultures in the absence of these compounds. A selective toxicity for transformed cells appeared to exist for the beta-carotene-treated F-17 cells. This apparent selective toxicity was not observed in another line of transformed cells. Cl 16 cells, or in human cells. We observed different uptake patterns of beta-carotene by nontransformed C3H10T1/2 cells, F-17 cells, and Cl 16 cells that may account for the observed apparent selective toxicity of one line of transformed cells (F-17 cells) to beta-carotene. PMID- 7877893 TI - Modification of the effect of tamoxifen, cis-platin, DTIC, and interferon-alpha 2b on human melanoma cells in culture by a mixture of vitamins. AB - The effect of a mixture of vitamins in modifying the efficacy of commonly used drugs in the treatment of human melanoma has not been studied. Vitamin C and d alpha-tocopheryl succinate (alpha-TS) alone reduced the growth of human melanoma (SK-30) cells in culture, whereas beta-carotene (BC), 13-cis-retinoic acid (RA), or sodium selenite alone was ineffective. RA caused morphological changes, as evidenced by flattening of cells and formation of short cytoplasmic processes. A mixture of four vitamins (vitamin C, BC, alpha-TS, and RA) was more effective in reducing growth of human melanoma cells than a mixture of three vitamins. The growth-inhibitory effect of cis-platin, decarbazine, tamoxifen, and recombinant interferon-alpha 2b was enhanced by vitamin C alone, a mixture of three vitamins (BC, alpha-TS, and RA), and a mixture of four vitamins (vitamin C, BC, alpha-TS, and RA) that contained 50 micrograms/ml of vitamin C. These data show that a mixture of three or four vitamins can enhance the growth-inhibitory effect of currently used chemotherapeutic agents on human melanoma cells. PMID- 7877894 TI - Dietary fat affects plasma prolactin in female F344 rats under conditions of ether stress. AB - The influence of amount and type of dietary fat on circulating concentrations of prolactin and estradiol-17 beta in female F344 rats from which blood was sampled by decapitation under ether anesthesia was compared with that in rats from which blood was collected without anesthesia. The animals were fed isonutrient (adjusted for differences in energy density) semipurified diets containing 5% or 20% (by weight) sunflower seed oil or lard. Blood was sampled by decapitation with or without standardized ether anesthesia during the afternoon of proestrus estrus or the morning of metestrus-diestrus, as determined by examination of vaginal smears. Plasma hormone concentrations were measured by radioimmunoassay. Prolactin levels were lower during proestrus-estrus in rats fed a low-fat diet than in animals fed a high-fat diet, statistically independent of the type of dietary fat, but only when blood was sampled by decapitation under ether anesthesia [p = 0.0384, 2-way analysis of variance (ANOVA)]. No such difference was found in rats decapitated without anesthesia. This effect of amount of dietary fat on prolactin in proestrus-estrus animals anesthetized with ether was predominantly present in animals fed polyunsaturated fat (p < 0.05, 1-way ANOVA and Tukey's test) and was statistically not significant in rats fed saturated fat diets. During metestrus-diestrus, prolactin levels were significantly lower in animals fed a high-saturated fat diet than in those fed low-saturated fat, low unsaturated fat, or high-unsaturated fat diets, independent of the blood sampling conditions (p < 0.05, 2-way ANOVA and Tukey's test). No consistent effects on estradiol-17 beta levels were found in type or amount of dietary fat or in presence or absence of ether anesthesia before decapitation. Growth, apparent digestibility of fat, and caloric intake were similar in all four dietary groups, but food consumption was higher and food conversion efficiency was lower in animals fed low-fat diets than in those fed high-fat diets. This study confirms the hypothesis that effects of dietary fat, particularly polyunsaturated fat, on circulating prolactin occur only during (ether) stress. Because stress is a frequent and normal phenomenon, this observation implies that the mammary glands of animals with a high dietary intake of polyunsaturated fat are frequently exposed to higher circulating prolactin concentrations than rats fed a low-fat diet, which may be a major mechanism by which dietary fat enhances rat mammary carcinogenesis. PMID- 7877895 TI - Expression of mRNA for the gap-junctional protein connexin43 in human colonic tissue is variable in response to beta-carotene supplementation. AB - Increased expression of the gap-junctional protein connexin43 (Cx43) is reported to be increased in mouse and human dermal fibroblasts in vitro in response to beta-carotene treatment. In the present study, we determined the level of Cx43 mRNA expression in colonic mucosa from normal subjects and subjects with a prior history of colonic polyps or cancer before and after three months of administration of a placebo or beta-carotene. RNA was reverse transcribed and used in a polymerase chain reaction assay employing primers selected from the human Cx43 gene sequence. Cx43 mRNA expression was normalized on the basis of beta 2-microglobulin mRNA expression. The beta-carotene concentration in colonic mucosa, as well as serum and diet, was also determined to establish a correlation between Cx43 expression and beta-carotene concentration. In an initial analysis of samples collected from 10 subjects before supplementation, the quantity of Cx43 mRNA was variable and did not correlate with beta-carotene intake or the concentration of beta-carotene in tissue or serum. In samples collected at zero and three months from eight subjects who were controls or received a placebo, there was no correlation between Cx43 mRNA level and tissue or serum beta carotene concentration. In samples collected from subjects before and after three months of beta-carotene supplementation, there was a significant increase in tissue and serum beta-carotene concentration in all subjects and an increase in Cx43 mRNA expression after supplementation relative to baseline in four of six samples. The high variability in Cx43 expression indicates that induction of Cx43 mRNA expression is not solely dependent on the concentration of beta-carotene in diet, serum, or tissue. However, the results from subjects supplemented with beta carotene suggest that induced expression may occur in colonic tissue of some individuals. some individuals. PMID- 7877896 TI - Dietary fibers stimulate colonic cell proliferation by different mechanisms at different sites. AB - The effect of dietary fiber type (cellulose, pectin, or oat bran) on colonic short-chain fatty acids (SCFA), luminal pH, and epithelial cell proliferation was examined in 60 male Sprague-Dawley rats. In vivo cell proliferation was measured by [3H]thymidine incorporation into DNA, pH was measured in vivo, and luminal SCFA were determined by gas chromatography. The pectin and oat bran diets produced higher concentrations of all types of SCFA and total SCFA than cellulose at every site. The higher the SCFA concentration, the lower was the pH at each site. In the cecum, the concentration of SCFA was positively associated with the number of cells per crypt column (r = 0.961), total cells per crypt (r = 0.963), and the proliferative zone (r = 0.845). In contrast, in the distal colon, there was no significant correlation between SCFA concentration and measurements of cell proliferation. These data suggest that fiber stimulates cecal cell proliferation through the production of SCFA. The effects of fiber on distal colonic cytokinetics are likely mediated through a different mechanism. PMID- 7877897 TI - Effect of beta-carotene on spontaneous and X-ray-induced chromosomal damage in bone marrow cells of mice. AB - The effect of beta-carotene on spontaneous and X-ray-induced chromosomal damage in bone marrow cells of mice was studied. As a source of beta-carotene, dried Dunaliella bardawil (containing 6% beta-carotene) or oil suspension of Dunaliella beta-carotene was used. In Experiment 1, mice were given a basal diet, a 0.5% Dunaliella diet, or a 4% Dunaliella diet for four weeks. In Experiment 2, mice were given an oil suspension of Dunaliella beta-carotene (300 mg/kg body wt) by gavage for seven days while being fed a fat-rich diet. After beta-carotene treatment for the indicated time, spontaneous and X-ray (0.3 Gy, whole-body) induced chromosomal damage in bone marrow cells was evaluated in terms of the percentages of micronucleated reticulocytes in their peripheral blood. The beta carotene treatment slightly lowered the spontaneous and X-ray-induced chromosomal damage in bone marrow cells. Despite the higher doses of beta-carotene, the concentrations of beta-carotene in bone marrow, liver, and serum were much lower than those of vitamin E. In addition, the beta-carotene treatment markedly lowered the concentration of vitamin E in the tissues. PMID- 7877899 TI - Aggression, trauma, and hatred in the treatment of borderline patients. AB - This article focuses on the etiology of aggressive affect, behavior, and fantasy in the treatment of patients with severe personality disorders in an effort to further our understanding of the psychopathology and treatment of these patients. In the process, the relationship between inborn disposition to aggressive behavior and the effect of severe trauma and psychosocial pathology in early childhood are examined. Various types of transferences marked by aggression and specific approaches to each of these are outlined. Particular reference is given to the management of intense hatred--as a derivative of aggression--in the transference, and of the unconscious identification with both victim and victimizer in patients who have experienced sexual or physical abuse. PMID- 7877898 TI - Effect of iron deficiency on DMH-induced gastrointestinal tract tumors and occurrence of hepatocyte abnormalities in Fischer rats. AB - The relationship between iron deficiency and carcinogenesis was studied using the carcinogen dimethylhydrazine to induce gastrointestinal tumors in Fischer 344 control and iron-deficient rats. Dimethylhydrazine (30 mg/body wt) was administered by gastric intubation 10 times over nine weeks. After 32 weeks, rats were sacrificed, and tumor incidence was assessed. The overall incidence of gastrointestinal tract tumors (colonic and duodenal) was higher in the iron deficient (66%) than in the control group (46%). Whereas the incidence of colonic tumors was identical in control and iron-deficient groups, the duodenal tumor incidence was significantly elevated in iron deficiency. Five of 15 rats, i.e., 33.3%, in the iron-deficient group developed duodenal tumors; in the control group, only 1 of 15 rats developed a tumor (i.e., 6.6%). Also, iron-deficient rats had multiple tumors. Histological examination of the colon and duodenum revealed that the tumors were adenocarcinomatous in nature. Another notable feature in the iron-deficient group was the presence of atypical cells in the livers of carcinogen-treated iron-deficient rats. This study thus suggests that there is a greater incidence of tumors in iron deficiency and that the proximal part of the intestines seems to be the preferred site. The presence of atypical cells in the liver suggests that in iron deficiency, besides gastrointestinal tract tumors, the liver may also be a favored site for abnormalities. PMID- 7877901 TI - Rethinking the comparison of borderline personality disorder and multiple personality disorder. AB - This article has made a number of points that assert what is today a minority position within the fields of MPD/DID and BPD. We hope our views will stimulate attempts by others to rethink their positions and test our assertions, so that issues surrounding these two disorders can be sharpened. For the sake of the clarity of future work, we summarize in outline form the essence of our viewpoint. 1. BPD and MPD/DID have similar appearing symptoms, such as identity problems, unstable affect modulation, self-destructive behaviors, chaotic impulse control, and troubled interpersonal relationships, but they have decisive differences in underlying dynamics, process, and structure. 2. DSM tends to blur these two disorders by its emphasis on phenomenology over inner structure, thus fostering misleading conclusions when DSM criteria are used to test for comorbidity or overlap between BPD and MPD/DID. 3. BPD and MPD/DID are both described dynamically as using the defense of splitting, but we contend that the splitting in each disorder is fundamentally different from the splitting in the other. BPD uses a polarization form of splitting, whereas MPD/DID uses ego splitting or identity division. 4. Both disorders partake in the process of dissociation, but the quality of dissociation in BPD is a "low-tech" spaced out type, whereas that of MPD/DID is a "high-tech" waking dream. 5. BPD structure is also "low tech," with polarization of self, object, and relationship. MPD/DID structure is "high tech," with heavily symbolic, highly nuanced variations of self, object, and relationship. 6. Although both conditions have etiologic elements of trauma, BPD has a larger degree of developmental deficiency, with a failure to complete the task of entering a repression hierarchy of defenses. MPD/DID, by use of primary process-linked symbolic dissociation, is able to continue development to the repression hierarchy, although at a profound cost of simultaneous suspension of reality testing. BPD patients suffer from the rigid use of too few defenses; MPD/DID patients suffer from the obsolete use of too many defenses. 7. BPD patients grow up in homes in which overtly expressed aggression is more tolerated, or at least more openly experienced. MPD/DID patients grow up in homes in which the fact of aggression is kept a secret. This has consequences for the formation of psychic structure in each disorder.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7877900 TI - Splitting as a consequence of severe abuse in childhood. AB - Clinical data suggest that Kernberg's description of splitting as a defense mechanism is useful in conceptualizing the psychological consequences of abuse in childhood in certain patients. The splitting in these patients is similar to his description of splitting in borderline patients in that it compartmentalizes and sequesters certain overwhelming and painful ego states accompanying negative introjects of the betraying primary object and the betrayed self. These sequestered introjects, furthermore, act as automatons, generating behaviors that arbitrarily re-enact their content even though the patient remains consciously unaware of their historical meaning. Another consequence of the sequestration of these traumatic introjects is that their affects retain their initial power and primitive quality, unmodulated by the usual homogenizing process that is a part of the synthesis of part-object introjects into whole-object introjects; the sequestration, therefore, often painful in itself, must nevertheless be rigidly maintained lest traumatic anxiety in the face of overwhelming affects be re experienced. Shengold calls the sequence of events that results in this brittle but stubborn painful constriction of the personality "soul murder." He borrowed the phrase from Freud who used it to refer to what Schreber had suffered at the hands of his sadistic father. That phrase--"soul murder"--may sound melodramatic, but it powerfully conveys what these patients communicate of their experience of themselves. As with Kernberg's patients, the defensive splitting serves to protect the positive introjects. These patients fear their negative introjects, even more than they feel uncomfortable about the split. They fear their desperate rage will destroy their love objects, and leave them feeling abandoned and hating themselves. As one of my patients put it: "I fear that my destructive anger will leave me all alone in a sea of rubble of my own making." In the transference, he feared destroying me and our positive bond. In these cases it would seem that the turning to splitting occurred at a later age than it does with Kernberg's borderline patients. His proposition is that the developmentally normal "splitting," related to the undifferentiation of the infantile ego, persists as a defensive splitting, perhaps as a consequence of a consistently derailed mother child dialogue; whereas in my patients it would seem that the normal developmental splitting had waned as ego differentiation proceeded, but that in the face of overwhelming traumata at perhaps 3 or 4 years of age, the primitive defense was invoked regressively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7877902 TI - Characterologic subtypes of the borderline personality disorder. With a note on prognostic factors. AB - Borderline personality disorder (BPD), as defined by DSM, is heterogeneous with respect to the array of the personality traits patients may exhibit. Thus, the characterology of BPD admits of many subtypes. From the standpoint of DSM-Axis II, BPD is almost always associated with a complex personality pattern that meets criteria for several other Axis II disorders--which may then be viewed as characterologic subtypes. Usually these will be from the same "dramatic cluster" to which BPD itself belongs; namely, histrionic, narcissistic, or antisocial. But any of the Axis II disorders may be found in conjunction with BPD, "schizoid" being the rarest accompaniment. The Kraepelinian temperaments (depressive, manic, irritable, cyclothymic) constitute another set of subtypes. There is prognostic significance to these diagnostic subdivisions. Irritable and antisocial types predict poor outcome. The poorest prognosis results when antisociality is admixed with psychopathy. Obsessive-compulsive traits, especially self-discipline and orderliness, are associated with good outcome. A number of individual personality traits are found with especial frequency in BPD and may be viewed as finer-scale subtypes. Their presence influences the direction in which therapeutic efforts must be directed and also affects long-term outcome. These traits include mercurial, unreasonable, infantile, volatile, demanding, and going-to-extremes. In general, the nature and intensity of all the traits relevant to each BPD patient (especially those that are "offensive" or socially alienating), and the balance between negative and positive traits, account for much of the variance in ultimate response to treatment and in eventual outcome. PMID- 7877903 TI - Shame, compassion, and the "borderline" personality. AB - This article focuses on the emotionality of the individual diagnosed as "borderline." There may be no clinical condition characterized by so wide a range of affective expression. The author points out that both Kernberg and Kohut view this cohort from the standpoint of drive theory, in which all emotion is traced to drive forces gone awry. Viewed from the perspective of affect theory, it becomes possible to explain this otherwise puzzling cluster of symptoms as the expression of and defenses against the painful emotion of shame. The very concept of a "borderline" illness may prove to be a construction made necessary by previous misunderstanding of shame psychology, and the symptoms themselves perhaps an artifact of a wider, societal misunderstanding of shame. PMID- 7877904 TI - Dracula. Disorders of the self and borderline personality organization. AB - It has been proposed that Bram Stoker's novel Dracula can best be understood as a dramatic, hyperbolic, and fantastic expression of themes consistent with contemporary psychoanalytic conceptions of borderline personality disorder organization. Such an understanding may, in turn, shed further light on the nature of the intrapsychic world and experiences of borderline patients. Excerpts from the novel can be used to support the conceptualization of recent contributions to object relations theory and the understanding of borderline personality organization. It is uncanny how consistent Dracula's characteristics are to the generally seen complaints of patients suffering from this disorder. PMID- 7877905 TI - A profile of specific psychotherapeutic actions for borderline psychopathology. Psychotherapeutic psychoanalysis. AB - This article has attempted to catalog additions to the psychotherapeutic armamentarium in the treatment of borderline personality disorder based on their conceptual linkage with new paradigms derived from contemporary developments in psychoanalysis. These new therapeutic actions have broadened and increased our therapeutic skills and are now also viewed as essential for bringing about change in patients with severe developmental arrests. The term psychotherapeutic psychoanalysis is suggested to encompass this unique cluster of intrinsic and extrinsic treatment factors within the framework of psychoanalysis. PMID- 7877906 TI - Treatment of borderline patients in a multiple-treater setting. AB - For all the problems and challenges inherent in a multiple-treater setting, there are great advantages in being part of a treatment team. Colleagues provide a holding and containing function for each other in the treatment of these extraordinarily difficult patients. Marcus observed that "the problem with the sickest patients is that the affects are uncontainable by a single individual. The affects are more easily containable by the group, because at any one moment some members are not under direct threat and, therefore, can maintain an observing ego" (p 251). The different treatment relationships offer the borderline patient numerous opportunities to internalize new modes of object relatedness through the process of reintrojecting what they have projected into others. The cumulative effect of a group of caring professionals who are doing their best to process and understand what is happening can be highly therapeutic. PMID- 7877907 TI - Countertransference in the treatment of the borderline personality. AB - The emotional pressure and transferences of patients to their physicians and other caregivers are natural, inevitable occurrences that are not restricted to therapeutic situations in which one is using a dynamic approach. Transferences are present in all relationships but are scrutinized in intensive dynamic psychotherapy. This article presents clinical examples that illustrate the intense pressures, often near-psychotic, exerted by certain borderline patients, which are unconsciously targeted to force a specific type of response from the therapist. PMID- 7877908 TI - Cytomegalovirus infections. PMID- 7877909 TI - Clinical manifestations of scleroderma. PMID- 7877910 TI - Retinopathy of prematurity. AB - Retinopathy of prematurity is a common disorder among extremely low-birthweight preterm infants and may cause total vision loss in as many as 2% to 4% of those weighing less than 2 pounds at birth. Regular examinations begun in the neonatal intensive care unit permit early detection and treatment of progressive ROP and allow a reduction in visual impairment. Infants whose ROP has regressed should continue to receive regular ophthalmologic follow-up for the detection and treatment of myopia and strabismus and, if they have cicatricial sequelae, late retinal detachments as teens or adults. Early intervention and special education programs are important for the children whose vision loss is significant. PMID- 7877911 TI - Separation anxiety. PMID- 7877912 TI - Proper use of the clinical microbiology laboratory. AB - The interaction between clinicians and microbiology laboratory staff has to be one of mutual benefit. The more the laboratory personnel know about your patients, the more meaningful and thorough will be the results. Communication is the key to success. Visit the microbiology laboratory and get to know the staff. The clinician also needs to be familiar with and use the most commonly used diagnostic tests for individual bacterial pathogens appropriately. PMID- 7877913 TI - Consultation with the specialist. Hoarseness. PMID- 7877914 TI - Chronic cough. PMID- 7877915 TI - Thumbsucking. PMID- 7877916 TI - Medical record review. Staying focused: documenting the management of a child who has an attentional disorder. PMID- 7877917 TI - Chronology of the management of a child who has ADHD. PMID- 7877918 TI - Blindness and visual impairment. PMID- 7877919 TI - Pleural effusions: diagnostic considerations. PMID- 7877920 TI - Reiter's syndrome. A possibility in patients with reactive arthritis. AB - Reiter's syndrome is an often overlooked and misdiagnosed complex of symptoms. Patients may not present with the classic triad of symptoms, or they may forget to mention other pertinent manifestations. How can you make an accurate diagnosis? And what is an effective approach to management? Dr Kirchner reviews studies on the epidemiology, causes, and pathogenesis of the syndrome and discusses key factors in clinical evaluation and treatment. PMID- 7877921 TI - Hantavirus pulmonary syndrome. Outbreak of a new disease caused by a new virus. AB - Only months after the first report of a brief prodromal illness followed by rapidly progressive noncardiogenic pulmonary edema and death, the causative agent was tentatively identified as a previously unknown hantavirus. Although hantaviral infections are well known in Asia, none had ever been reported in the United States. A collaborative effort between local, state, regional, and federal authorities allowed rapid identification of a new set of clinical and laboratory findings, now known as the hantavirus pulmonary syndrome. Inclusion, exclusion, and confirmatory criteria have been established to help identify potential cases. However, tests for the infection are still experimental, so physicians should send samples to the Centers for Disease Control and Prevention for testing in suspected cases. Ribavirin (Virazole) may be beneficial early in the course of hantavirus pulmonary syndrome, and supportive care is essential. Rodents, particularly the deer mouse in the Southwest, are the natural hosts for the hantaviruses. Prevention of this new syndrome centers on avoidance of contact with and inhalation of saliva, urine, and feces of infected rodents. PMID- 7877922 TI - Other people's money. The big problem in healthcare. PMID- 7877923 TI - Menstrual dysfunction in athletes. How to identify and treat patients at risk for skeletal injury. AB - Menstrual dysfunction is a common problem in competitive athletes. Exercise intensity, hypothalamic immaturity, and dietary practices are contributing factors. Although the specific mechanism is unknown, disruption of hypothalamic functioning appears to be involved. Women with menstrual dysfunction are at increased risk for bone mineral loss and musculoskeletal injury. Primary care physicians should routinely screen for these abnormalities and should be alert to the possibility of an eating disorder. Treatment options include a reduction in training intensity, improved nutrition and caloric intake, and hormone therapy to prevent bone loss and allow for safe continuation of training. PMID- 7877924 TI - Eosinophilia of the blood. A search for the cause uncovers squamous cell carcinoma. AB - When laboratory evaluation uncovers eosinophilia of the blood, an extensive investigation is sometimes required to identify the cause. Parasitic infections and neoplastic, idiopathic, and collagen vascular diseases have been linked to abnormally high blood concentration of eosinophils, as have allergic reactions and adrenal insufficiency. Treatment should be directed at the underlying cause once it has been identified. The case discussed here was particularly interesting and unusual because the patient had nonspecific symptoms and marked eosinophilia of the blood, but initial laboratory test results and physical examination findings did not offer any diagnostic clues. PMID- 7877925 TI - Losing our way. PMID- 7877926 TI - How big a role for government in medicine? PMID- 7877927 TI - Diagnostic cardiac catheterization. When is it appropriate? AB - Cardiac catheterization is a low-risk procedure that provides information on cardiac and coronary artery anatomy, hemodynamic parameters, and valvular function. Not all patients with cardiac symptoms need the procedure. Most patients should have noninvasive screening procedures before referral for diagnostic cardiac catheterization. Obviously, not all patients clearly meet strict criteria, and making decisions in "borderline" cases demands clinical judgment. The recommendations given here are a combination of ACC/AHA guidelines and standards defined in current literature. PMID- 7877928 TI - Transesophageal echocardiography. When is it superior to standard imaging in clinical practice? AB - Echocardiography is invaluable in assessing patients with known or suspected cardiac disorders. However, there are often impediments to adequate imaging using the standard transthoracic route (eg, mechanical ventilation, bandages). Transesophageal imaging overcomes many of these technical limitations and, as one researcher notes, provides a "new window to the heart." Drs Peterson and Orsinelli review common clinical applications of the procedure and adjunctive uses. PMID- 7877929 TI - Central venous catheters. Placement and monitoring tips. AB - Placement of a central venous catheter is not without risk. If the tip of the catheter either is inadvertently positioned within the heart or migrates into it, vascular erosions may develop and result in perforation and death. In this article, Dr Kahn gives the advantages and disadvantages of the usual routes of insertion and describes monitoring techniques. He also suggests methods of avoiding initial intracardiac placement. PMID- 7877930 TI - A practical approach to dizziness. Questions to bring vertigo and other causes into focus. AB - Evaluation of a patient presenting with dizziness begins with and largely depends on the patient's history. The diagnosis often can be accurately determined in a primary care setting when a stepwise algorithmic approach is used. The first step is getting a detailed account of precisely what the patient means by "dizziness." This helps determine whether the cause is vertigo or another condition, such as orthostatic hypotension. Establishing whether the vertigo is central or peripheral in origin and, if peripheral, how long episodes last further focuses the investigation. Certain clues on physical examination and appropriate use of diagnostic tests help support the diagnosis. Referral should be contemplated when significant central disease is suspected and when vertigo of peripheral origin is persistent or atypical. PMID- 7877931 TI - Methadone maintenance treatment. When and how to refer patients. AB - Methadone, a long-acting oral narcotic analgesic, prevents withdrawal symptoms and craving over a 24-hour period in patients addicted to narcotics. Methadone maintenance treatment programs have been shown to decrease criminal behavior, improve psychosocial functioning, and decrease injecting narcotic use, thus reducing the spread of AIDS. For primary care physicians, knowing when and how to refer a patient to methadone maintenance treatment, as well as ensuring ongoing liaison with the treatment program, can help improve the quality and continuity of care for addicted patients. PMID- 7877932 TI - Neuromuscular diseases of the gastrointestinal tract. Specific disorders that often get a nonspecific diagnosis. AB - Gastrointestinal motor dysfunction, intestinal pseudo-obstruction syndromes, and hollow visceral neuropathy and myopathy were previously considered functional bowel diseases but are now recognized to be organic disorders. They may alter the muscle of the intestinal wall or the nerves of the myenteric plexus, or both. Their symptoms of chronic unexplained abdominal pain, abdominal distention and bloating, early satiety, nausea, vomiting, and alternating diarrhea and constipation are the most common and perhaps the most difficult problems encountered by gastroenterologists. New intestinal recording devices assess motility and allow objective classification of neuromuscular disease, permitting accurate diagnosis and better treatment. PMID- 7877933 TI - Genotype by environment interactions in laying hens based on relationship between breeding values of sires in temperate and tropical environments. AB - This study was conducted to evaluate the significance of genotype by environment (G x E) interactions for tropical poultry breeding. Three environmental conditions were considered: controlled normal-temperature (20 +/- 2 C, CN) and controlled high-temperature (32 C, CH) housing in Germany as well as natural open tropical housing in Malaysia (22 to 34 C, TO). Eighty-four sires were considered as genotypes. Their 5,352 progeny were tested simultaneously over three environments. For each sire, its part breeding value (BV) was estimated within each environment for each performance trait. Correlations between these BV for a pair of environments were used to estimate the magnitude of G x E interactions and the degree of relationship between them to demonstrate their implications on breeding strategies. Differences between observed and expected genetic correlations of BV for body weight, egg weight, egg number, egg mass, feed intake, and production efficiency as a fraction of the expected correlation were 5.1, 4.0, 36.7, 36.5, 17.7, and 31.6%, respectively, suggesting greater significance of G x E interactions for reproduction and production efficiency. The relationships between BV over the three environments were linear for most of the traits studied, but the coefficients of determination were dependent upon the magnitude of interactions involved. Relative efficiencies of indirect selection in CN or CH for performance in TO were also very low. PMID- 7877934 TI - Growth, livability, and feed conversion of 1957 vs 1991 broilers when fed "typical" 1957 and 1991 broiler diets. AB - The relative contributions of genetic selection and dietary regimen on the performance of broilers was assessed. Body weight, feed consumption, mortality (M), and the degree of tibial dyschondroplasia (TD) were measured in the 1957 Athens-Canadian Randombred Control (ACRBC) strain of broilers and in the 1991 Arbor Acres (AA) feather-sexable strain when fed "typical" 1957 and 1991 diets. Energy and protein levels, vitamin and mineral packs, and the coccidiostats used in the two dietary regimens were chosen to be representative of those in use by the industry for the two time periods. Eight treatment groups, i.e., two strains, two sexes, and two dietary regimens, were assigned into four blocks of eight litter floor pens for grow out. The 1957 diets were fed as mash, and the 1991 starter and grower diets were fed as crumbles and pellets, respectively. Feed consumption and BW were recorded at 21, 42, 56, 70, and 84 d of age, a period covering the normal marketing ages for the two broilers. Mortality and the cause of death was recorded daily. The incidence and severity of TD was assessed using a Lixiscope at 42 d of age. Average BW were 190, 508, 790, 1,087, and 1,400 g for the ACRBC on the 1957 diets vs 700, 2,132, 3,108, 3,812, and 4,498 g for the AA on the 1991 diets at 21, 42, 56, 70, and 84 d of age, respectively. The 1991 diets increased the BW of the AA by an average of 14% (20% at 42 d, but only 8% at 84 d) and of the ACRBC by 22%. The BW advantage for the 1991 diet over the 1957 diet for the AA was less for males than for females after 42 d of age, and the advantage decreased with age, probably due to the increasing incidence of leg problems. The M for AA was 9.1% vs 3.3% for the ACRBC at 42 d. Most of the ACRBC M occurred before 21 d, whereas M occurred throughout for the AA, with most after 21 d due to flip-overs and ascites. The feed conversion at 42 d for the ACRBC on the 1957 diet was 3.00 vs 2.04 for the AA on the 1991 diet. The AA on the 1991 diet had a 48.6% incidence of TD vs 25.6% on the 1957 diet. The ACRBC had approximately 1.2% TD on both diets. The TD was more severe with the 1991 diet. PMID- 7877935 TI - Carcass composition and yield of 1991 vs 1957 broilers when fed "typical" 1957 and 1991 broiler diets. AB - Whole carcass yield and the yield of parts (i.e., wings, saddle and legs, Pectoralis major, Pectoralis minor, breast skin, rack, abdominal fat pad, heart, and lungs), as well as whole carcass analysis for fat, moisture, and ash, were measured in the 1957 Athens-Canadian Randombred Control (ACRBC) and in the 1991 Arbor Acres (AA) feather-sexable strain, when fed "typical" 1957 and 1991 diets. Using the average of both sexes, the carcass weights of the 1991 birds on the 1991 diets were 4.4, 3.9, and 3.5 times heavier than those from the 1957 ACRBC on the 1957 diet at 43, 71, and 84 d of age, respectively. Birds fed the 1991 diets had significantly heavier carcass weights than those fed the 1957 diets. Hot carcass yield of the AA broiler (mean of both sexes) was approximately 6 to 7% higher at the same age than for the ACRBC. Water uptake in the carcass (following a 60-min immersion in ice water) was approximately 2 to 2.5% higher in the ACRBC than in the AA broiler. Yield of saddle and legs as a percentage of live BW was about 4% higher in the AA than in the ACRBC. Dietary regimen did not affect the yield of saddle and legs. Males had 2 to 3% more saddle and legs than the females. The yield of total breast meat for the AA was approximately 3% higher (mean = 16.9%) than for the ACRBC over both sexes and all ages. Breast yield on the 1991 diets was approximately 1.2% higher for the AA than for the ACRBC. Females had slightly higher breast yield (1%) than males. The AA broiler had consistently heavier fat pads and higher percentage carcass fat at the same age and on the same diet than did the ACRBC. The percentage carcass fat was significantly higher on the 1991 vs the 1957 diet and in females vs males. The male-female difference in percentage carcass fat increased with age. Heart and lung size as a percentage of live BW were lower in the AA than in the ACRBC. PMID- 7877936 TI - A comparison of the immune performance of a 1991 commercial broiler with a 1957 randombred strain when fed "typical" 1957 and 1991 broiler diets. AB - The general objective of the present study was to assess the contribution that changes in genetic selection and dietary regimen have made on the immune performance of broilers. Chicks were hatched from 1991 and 1957 strains and placed on diets thought to be typical of those fed during 1957 and 1991. Immune responses were measured as total, IgM, and IgG antibody production, macrophage, and natural killer (NK) cell functions. Significant differences were observed between strains in antibody production. For example, 1957 males fed 1957 diets had the highest total (P < .0001), IgM (P < .0016), and IgG (P < .015) anti-sheep red blood cell antibodies as compared with all other strain-diet-sex groups. Both strains behaved similarly in terms of inflammatory macrophage recruitment, substrate adherence potential, and in the phagocytosis of sheep red blood cells. A greater percentage of the 1991 strain birds exhibited NK cell activity than all other groups. These studies suggest that genetic selection towards enhanced performance traits has negatively influenced the adaptive arm of the immune system (antibody production) with little or no effect on the nonadaptive components (macrophage and NK functions). PMID- 7877937 TI - Production and quality of eggs from sex-linked imperfect albino (sal-s) and nonalbino (s+) hens kept under commercial conditions. AB - The beneficial effects of the gene for imperfect albinism on egg production were investigated under commercial conditions. In one line (Line 8) but not in another (Line 3), hen-day egg production of albinos from 46 to 75 wk of age was higher than that of nonalbinos (76.1 vs 72.6%) resulting in higher overall hen-day (71.1 vs 69.3%, P < .08) and hen-housed (276.3 vs 263.6 eggs) egg production by albino hens. Egg production of Line 8 albinos was not different than that of one of two commercial strains (Strain A) included as a control (76.1 vs 75.6%, P > .05). In data from Lines 3 and 8 combined, sexual maturity of albinos was delayed by 3.0 d. Mortality was higher for albinos than nonalbinos (3.6 vs 1.8%) during the first 2 wk of brooding and lower for albinos (5.8 vs 8.9%) during the laying period. Eggs from albinos weighed less (53.8 vs 55.3 g), had smaller yolks (16.9 vs 17.6 g) and shells (5.16 vs 5.27 g), and firmer albumen (5.9 vs 5.6 mm). The results suggest that the gene produces beneficial effects on egg production under commercial conditions. PMID- 7877938 TI - Animal model analysis of genetic (co)variances for growth traits in Japanese quail. AB - Records of 1,530 Japanese quail were used to estimate heritabilities and genetic correlations based on a derivative-free restricted maximum likelihood (REML) method with an animal model and ANOVA. The animal model included fixed effects of hatch and sex, random effects of additive genetic value of the bird, and common environmental effect of the dam. Heritabilities estimated from REML for body weights at hatch, 7, 14, 21, and 28 d of age were .38, .12, .31, .12, and .44, respectively. Heritabilities estimates from the sire component of variance for the same traits were .57, .08, .28, .15, and .47. These values indicate that genetic progress can be made by selecting for either 14-d or 28-d body weight. Genetic correlation (REML) of .76 between body weights at 14 and 28 d of age indicates the possibility of improving body weight at 28 d of age by selecting for body weight at 14 d of age. PMID- 7877940 TI - Effects of eggshell quality and broiler breeder age on hatchability. AB - The effects of eggshell quality and breeder age were assessed on egg weight loss during incubation, fertility, hatchability, and embryonic mortality. The trials involved hatching eggs from three commercial broiler breeder flocks of the same strain but of different ages. The eggs were divided according to specific gravity into two groups, thin-shelled (< or = 1.080) and thick-shelled (> 1.080). Thin shelled eggs displayed a greater increase in weight with breeder age and greater weight loss during incubation. Thick-shelled eggs showed an increased hatchability as a result of greater fertility and lower intermediate and late embryonic mortalities. Percentage of culls, pips, and rots were not related to shell thickness. Eggs from the younger flock had a higher weight loss during incubation irrespective of shell thickness. Hatchability and viability (hatchability of fertile eggs) were lower in the younger flock due to increased early and late embryonic mortalities. Fertility, culls, and pips were not affected by breeder age. The data may indicate the extent to which recent innovations in breeder management and in incubation technology have changed patterns of fertility and embryonic mortality. PMID- 7877939 TI - Effects of dietary thiouracil on thyroid activity, egg production, and eggshell quality in commercial layers. AB - The effects of thyroid suppression induced during the rearing period by providing various dietary thiouracil (TU) regimens on plasma thyroxine (T4) concentrations, growth, and subsequent egg production (EP) and eggshell quality were determined in Single Comb White Leghorn chickens. Thiouracil was provided in the feed at levels of 0, .1, and .2% from 0 to 6 wk of age in Experiment 1, and at levels of 0, .05, and .1% from 6 to 16 wk of age in Experiment 2. In both experiments, T4 concentrations were reduced during TU treatment. However, T4 later became elevated at 12 and 20 wk in both dosage level groups in Experiment 1. Additionally, BW and egg weights were suppressed by both TU treatments, and EP was reduced up to Week 23 in the .1% TU-treated birds and through Week 25 in the .2% TU-treated birds. No effects on EP were noted in Experiment 2, but feed consumption (FC) was reduced during Week 6 in birds fed .05% TU and during Weeks 6, 10, and 19 in birds fed .1% TU. Both liver and thyroid weights were increased in .1% TU-treated birds relative to controls at Week 16. Eggshell quality was affected only in Experiment 2, in which birds given .05% TU had a higher relative conductance, or maximum rate of water loss, at Week 38 than 0 and .1% TU dosage levels, and .1% TU-treated birds had a higher breaking strength than 0 and .05% TU-treated birds at Week 22.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7877941 TI - The effect of beak trimming on two strains of commercial tom turkeys. 1. Performance traits. AB - Two commercial strains (Strains A and B) of tom turkeys were either beak trimmed or left with intact beaks. These strains responded similarly to beak trimming for performance traits, with the exception of a higher incidence of beak-inflicted injuries among Strain B toms with intact beaks. Turkeys with trimmed beaks had higher body weights at 8, 12, and 16 wk. Feed efficiency was better in beak trimmed birds from 4 to 8 wk, 12 to 16 wk, and 0 to 18 wk. Beak treatment did not effect mortality. Leg abnormalities caused the majority of culling or resulted in death or culling from beak-inflicted injuries. Beak trimming seems to be a beneficial practice in tom turkeys because feed efficiency of beak-trimmed toms was improved and injuries were reduced in a strain that tended to exhibit a high degree of beak-inflicted injuries. The results suggest that the need for beak trimming tom turkeys may be reduced when feed efficiency of toms with intact beaks is improved. PMID- 7877942 TI - Catecholamines modulate chicken immunoglobulin M and immunoglobulin G plaque forming cells. AB - Norepinephrine (NE) and epinephrine (E) function as chemical messengers in the central nervous and the endocrine systems of the chicken. The effects of in vivo and in vitro exposure of NE and E on IgM and IgG splenic plaque-forming cell (pfc) formation were determined to the antigen SRBC. Six-week-old Line UNH 105 New Hampshire chickens were injected i.v. with NE (500 micrograms/kg BW) or E (100 micrograms/kg BW) followed by 1 mL of 5% SRBC 30 min later. Five days after antigen injection, IgM and IgG pfc were assayed. Compared with controls, in vivo NE suppressed (P < .05) IgM and IgG pfc formation. In vitro NE treatment of splenic lymphocytes reduced (P < .05) IgM pfc but did not affect IgG pfc numbers. In vivo treatment with E increased (P < .05) IgM pfc whereas in vitro E exposure increased (P < .05) IgM pfc. Immunoglobulin G pfc were suppressed (P < .05) by both in vivo and in vitro E exposure. The presence of surface receptors for NE and E on splenic lymphocytes was determined using in vitro incubation with antagonists to alpha and beta receptors. These data suggest that there are alpha and beta receptor sites on lymphocytes for NE and E, and that these catecholamines have a regulatory role in plaque cell proliferation. PMID- 7877943 TI - Influence of amino acid supplementation of low-protein diets and metabolizable energy feeding sequence on performance and carcass composition of toms. AB - An experiment was conducted to determine the influence of essential amino acid (EAA) supplementation of low-protein diets and of MEn feeding sequence on performance and selected carcass characteristics of turkey toms. Feeding diets containing 93 or 100% of the protein and 100% of the EAA concentrations recommended by NRC (1984) or a diet containing 93 and 107% of the recommended protein and EAA concentrations, respectively, had no effect on BW or feed efficiency of toms at 104 or 117 d of age. Dietary protein-EAA concentrations also had no effect on carcass and breast meat yields or proximate composition of carcasses at 105, 112, or 118 d of age, irrespective of MEn feeding sequence. Feeding diets supplying 108% of the MEn concentrations (MH) listed by NRC from 41 to 104 d improved BW (P < .02) and feed efficiency (P < .01) as compared with feeding 102% (M) of the MEn listed by NRC, but only the improvement in feed efficiency was evident at 117 d. Feeding diets supplying 108% MEn from 41 to 104 d, followed by the 102% MEn diet from 104 to 117 d (MHM), resulted in the same 117-d BW and feed efficiency as feeding the MH MEn sequence from 41 to 117 d. Metabolizable energy feeding sequence had no consistent effect on carcass or breast meat yields. Feeding the MHM sequence decreased (P < .05) fat pad and carcass fat of toms processed at 105, 112, and 118 d, compared with the MH feeding sequence. However, fat pad and carcass fat of toms fed the MHM MEn sequence generally exceeded those of toms fed M MEn diets from 1 d to time of processing. PMID- 7877945 TI - Limiting order of amino acids in corn and soybean meal for growth of the chick. AB - Several experiments were conducted with crossbred chicks during the period 8 to 22 d posthatching to establish the limiting order of amino acids (AA) in corn and dehulled soybean meal (SBM) and in a corn-SBM mixture. Cecectomized adult cockerels were used to determine true AA digestibilities in both corn and SBM, and AA fortification levels were based upon bringing digestible AA levels to their ideal levels (expressed as a percentage of CP). Ideal ratios (percentage of lysine) used were Lys, 100; sulfur AA (SAA), 72; Arg, 105; Val, 77; Thr, 67; Trp, 16; Ile, 67; His, 37; Phe+Tyr, 105; and Leu, 111. Diets were fed at 10% CP, but they contained corn or SBM in amounts that would just meet the ideal concentration of the AA in greatest excess (Leu for corn; Phe for SBM). Thus, the corn diets contained only 5.6% CP from corn whereas the SBM diets contained only 8.0% CP from SBM. Diets were adjusted to 10% CP from AA additions, with glutamate varying as necessary. The limiting order of AA in corn was 1) Lys, 2) Thr, 3) Trp, 4) Arg, Ile, and Val, 5) Met+cystine, 6) Phe+Tyr, and 7) His. In SBM, the limiting order was 1)Met+cystine, 2) Thr, 3) Lys and Val, 4) nonspecific amino nitrogen, and 5) His. The order of limiting AA in the corn-SBM mixture was 1) Met, 2) Thr, 3) Lys, 4) Val, 5) Arg, and 6) Trp. PMID- 7877944 TI - Digestibility of water-soluble pectin and organic acid losses in intact or cecectomized adult cockerels. AB - Two experimental diets consisting of a basal diet either undiluted or diluted with 1% pectin-based gelling agent were given to intact or cecectomized adult cockerels for a balance experiment. The digestibilities of the water-soluble added pectin were 83.2 and 61.4% in intact and cecectomized birds (P < .05), respectively. Lactic acid excretion varied from 407 to 2,692 mg/kg, acetic acid from 790 to 1,214 mg/kg, propionic acid from 108 to 240 mg/kg, and butyric acid from 50 to 90 mg/kg dry matter intake. Organic acid excretions were the lowest for intact birds fed the basal diet and the highest for cecectomized birds fed the pectin diet. Addition of pectin induced an increase (P < .001) in organic acid excretion, especially for lactic acid in cecectomized birds. Organic acid excretion was greater (P < .001) in cecectomized than in intact cockerels. The increase in organic acid excretion induced by pectin addition amounted to 9 and 62% of the digested fraction of pectin in intact and cecectomized cockerels, respectively. The results showed the water-soluble nonstarch polysaccharides to be digested both in ceca and upper tract. It was also shown that the major part of organic acids produced from fermentation are absorbed in the ceca. PMID- 7877946 TI - Somatic and germline chicken chimeras obtained from brown and white Leghorns by transfer of early blastodermal cells. AB - Stage X blastodermal cells were isolated from freshly laid unincubated Brown Leghorn chicken eggs. Five hundred cells from Stage X Brown Leghorn embryos were injected into the subgerminal cavity of White Leghorn unincubated embryos exposed to 550 rad of gamma irradiation from a cesium-137 source. Of 712 White Leghorn embryos that were irradiated and injected with Brown Leghorn blastodermal cells, 52 (7.3%) survived to hatching. Somatic chimerism was examined in the melanocyte population and erythroid lineage. The presence of brown feathers indicating donor cell contribution to melanocyte pigmentation was observed in 23 (44%) out of the 52 hatched chicks. Analysis of blood DNA was performed using a probe that revealed an endogenous retroviral gag fragment specific for the donor genome. Three out of these 23 chimeric chickens exhibited the gag-specific fragment. To test germline chimerism, chickens that reached sexual maturity were mated with Brown Leghorns. Three somatically chimeric hens produced Brown Leghorn progeny at a rate of 30.7, 9.2, and 2.9% respectively, thus proving donor cell contribution to the germline differentiation. Chimeric chickens obtained after injection of nonirradiated embryos exhibited a lower extent of chimerism at the feather level and did not show any chimerism in the erythroid lineage and the germline, thus demonstrating the value of the use of compromised recipient embryos to produce chimeras in chickens. Nevertheless, the extent of somatic chimerism could not be used to predict the germline chimerism. PMID- 7877947 TI - Critical day lengths for egg production and photorefractoriness in the domestic turkey. AB - Critical day lengths (CDL) for ovarian growth, egg production, and photorefractoriness were estimated in turkey hens during winter and summer seasons. In two experiments, one in each season, fixed day length treatments ranging from 10.5 to 16 h/d were applied to photosensitive hens at 30 wk of age. Daily egg production was used to estimate CDL for the induction of egg production as well as optimal egg production. After 24 wk on light treatments, hens used during the winter season were exposed to 20 h light: 4 h dark and subsequent changes in egg production were used to evaluate photorefractoriness. In two additional experiments, a night-interruption design was used to evaluate CDL and ovarian photoresponsiveness during winter and summer. The CDL for inducing egg production varied by season and was estimated to be 10.5 h or less during winter and about 11 h during summer. Likewise, the CDL for optimal egg production varied by season, being 11 to 11.5 h during winter and > 14 h during summer. The CDL for photorefractoriness in winter photostimulated hens was between 12 and 12.5 h. It was concluded that CDL vary by season and are not fixed, but are dynamic characteristics of photoperiodic processes. Thus, photoresponsiveness of turkey hens changes by season. In addition, CDL for initiating egg production, stimulating egg production, and inducing photorefractoriness are all different, with the CDL for photorefractoriness being longest. PMID- 7877948 TI - Exclusion of chromosomal mosaicism in amniotic fluid cultures: determination of number of colonies needed for accurate analysis. AB - Most laboratories use the in situ or flask culture method and a two-stage approach to mosaicism detection. Determination of the optimum number of metaphases to be counted depends largely on whether or not the colonies that grow from the cells in the amniotic fluid can be considered independent. Previous statistical analysis of data from mixed male and female amniocyte cultures indicated that for mosaicism detection these colonies can be considered independent (Cheung et al., 1990). This analysis was repeated with a set of mosaic cases from two independent prenatal diagnosis programmes. The same degree of colony independence was found with this set of data. This result was used to calculate the level of mosaicism that is excluded at a particular confidence level when set numbers of colonies are analysed at each stage. The tables generated apply directly to the in situ method and with modification they can be used with the flask method. The conclusions are (1) analysis of cells from multiple colonies enhances the likelihood of excluding true mosaicism; (2) analysis of more than one metaphase per colony offers little advantage in excluding mosaicism; and (3) the two-stage approach is the most efficient. These conclusions should be used together with the expected clinical outcome of the actual cytogenetic abnormality, as discussed by Hsu et al. (1992). PMID- 7877949 TI - Swedish survey on extra structurally abnormal chromosomes in 39 105 consecutive prenatal diagnoses: prevalence and characterization by fluorescence in situ hybridization. AB - During 7 years (1985-1992), 39,105 consecutive prenatal diagnoses (34,908 amniocenteses and 4197 chorionic villus samples) were made at the five largest clinical genetic laboratories in Sweden. Thirty-one cases of extra structurally abnormal chromosomes (ESACs) were found, giving a total prevalence of 0.8 per 1000. Twelve ESACs were inherited, 14 were de novo and in five the parental origin was unknown. This gives an estimated prevalence of 0.3-0.4 per 1000 for familial and 0.4-0.5 per 1000 for de novo ESACs. Retrospectively, the ESACs were characterized by fluorescence in situ hybridization (FISH). In nine cases, no material was available for this analysis. In 21 of the remaining 22 cases, the chromosomal origin could be identified by FISH. Seventeen of these (81 per cent) were derived from the acrocentric chromosomes, of which 13 originated from chromosome 15 (62 per cent). The most common ESAC was the inv dup(15) (57 per cent). Two cases were derived from chromosome 22, one from chromosome 14, and one from either chromosome 13 or chromosome 21. The four remaining cases consisted to two i(18p)s and two small ring chromosomes derived from chromosomes 4 and 19, respectively. PMID- 7877950 TI - Prenatal diagnosis of the derivative chromosome 22 associated with cat eye syndrome by fluorescence in situ hybridization. AB - Cytogenetic studies of cultured amniocytes demonstrated a karyotype of 46,XX/47,XX, +mar. A bisatellited, dicentric, distamycin-DAPI negative, NOR positive marker was present in 76 per cent of the metaphases examined. Similar markers have been associated with cat eye syndrome (CES). We report on the utilization of fluorescence in situ hybridization (FISH) with a 14/22 alpha satellite probe and a chromosome 22-specific cosmid for locus D22S9 to determine the origin of the prenatally detected supernumerary marker chromosome. FISH studies demonstrated that the marker is a derivative of chromosome 22 and enabled us to provide the family with additional prognostic information. PMID- 7877951 TI - Prenatal ultrasonic diagnosis of obstructive bowel disease: a retrospective analysis. AB - Fetal obstructive bowel disease was diagnosed in 29 patients at 22-37 weeks (median 32 weeks) of gestation, seven (24 per cent) of whom also displayed other anomalies. Polyhydramnios was present in 20/29 cases (69 per cent). An abnormal karyotype existed in 7/29 cases (24 per cent), of which six were diagnosed prenatally (trisomy 21, n = 5; 69,XXX, n = 1) and one postnatally (trisomy 21). There was always an association with the ultrasonic 'double bubble' sign. Obstructive bowel disease was confirmed postnatally in 20/29 (69 per cent) cases, i.e., oesophageal atresia (n = 1), duodenal obstruction (n = 12), and small bowel obstruction (n = 7). Other anomalies existed in 6/29 (21 per cent) cases, i.e., multicystic kidney (n = 1) and multiple congenital anomalies (n = 5). The perinatal mortality rate was 35 per cent (7/20). PMID- 7877952 TI - Prenatal detection of trisomy 21 in uncultured amniocytes by fluorescence in situ hybridization: a prospective study. AB - A prospective study was undertaken to evaluate the use of fluorescence in situ hybridization (FISH) for the detection of trisomy 21 in interphase nuclei of uncultured amniotic fluid cells. Five hundred cases were analysed in situ and classified as normal or abnormal; the results were subsequently checked against the cytogenetic findings. Four hundred and ninety-three were correctly identified as normal with an 86.6 per cent average frequency of scored nuclei exhibiting two signals; six cases were correctly identified as trisomic for chromosome 21 with 81.7 per cent of scored nuclei exhibiting three signals; and one abnormal case involving an unbalanced chromosome 21:21 translocation was falsely scored as normal due to poor hybridization/detection efficiency. The method has been substantially improved and simplified so that it is suitable for the rapid detection of trisomy 21. As aneuploidy detection in interphase does not identify structural chromosome aberrations, it is not a substitute for fetal chromosome analysis. PMID- 7877953 TI - Accuracy of amniotic fluid testing before 21 weeks' gestation in prenatal diagnosis of congenital cytomegalovirus infection. AB - Cytomegalovirus (CMV) is the most common cause of intrauterine infection. Recent publications show amniocentesis to have an 81-100 per cent sensitivity in antenatal diagnosis after 21 weeks' gestation. Testing before 21 weeks' gestation is less well documented. We performed 36 amniocenteses between 14 and 20 weeks' gestation. The sensitivity was 45 per cent and the specificity 100 per cent. Implications and possible causes of this low sensitivity are discussed. PMID- 7877954 TI - Rapid prenatal diagnosis of aneuploidy from uncultured amniotic fluid cells using five-colour fluorescence in situ hybridization. AB - In this paper we describe the use of five-colour fluorescence in situ hybridization for prenatal diagnosis of aneuploidy using uncultured amniotic fluid cells. The analysis is based on ratio mixing of dual-labelled probes and digital imaging for the detection and visualization of five different probes specific for the five target chromosomes, 13, 18, 21, X, and Y. A retrospective blind analysis of 30 coded uncultured amniotic fluid samples correctly detected fetal sex and five trisomy 21 cases. Multicolour fluorescence in situ hybridization used in this way allows rapid and simultaneous detection of the most frequent aneuploidies. PMID- 7877955 TI - Diagnosis of Bloom's syndrome by sister chromatid exchange evaluation in chorionic villus cultures. AB - Cultures of a chorion biopsy taken from a pregnancy at risk of Bloom's syndrome revealed the high sister chromatid exchange frequency diagnostic of this rare disorder. To obtain the result, cultures were grown under standard conditions, with the addition of 10 microM 5'-bromodeoxyuridine for the final 48 h of incubation. This result demonstrates the feasibility of early prenatal diagnosis of Bloom's syndrome. PMID- 7877956 TI - Prenatal activity of a fetus with early-onset, severe spinal muscular atrophy. AB - A case of early-onset, severe spinal muscular atrophy is reported. Normal fetal breathing movement patterns and heart rate accelerations were observed in spite of the severe hypotonia evident at birth. PMID- 7877957 TI - The amplification refractory mutation system (ARMS): a rapid and direct prenatal diagnostic technique for beta-thalassaemia in Singapore. AB - beta-Thalassaemia major patients have chronic anaemia and since 3-4 per cent of Singaporeans carry the beta-gene, prenatal diagnosis is essential. We evaluated the amplification refractory mutation system (ARMS) technique as a routine test for prenatal diagnosis of beta-major. Six mutations along the beta-gene were studied--41-42 (-TCTT), IVSII #654 (C-T), 17 beta (A-T), -28 TATA (A-G), IVSI #5 (G-C), and IVSI #1 (G-T). Our results indicate that prenatal diagnosis using these mutations can be offered to 90 per cent (35/39) of our Chinese couples and 54.6 per cent (12/22) of our Malay couples at risk. Confirmation of ARMS results was carried out using allele-specific oligonucleotide hybridization. Prenatal diagnosis using ARMS was successfully carried out in nine cases which included a set of triplets and twins. The triplets were diagnosed with the beta-trait carrying the 41-42 mutation. The couple with twins possessed the #654 mutation and one twin was diagnosed with the beta-trait and the other with #654 homozygosity. Genomic sequencing of the undefined mutations in the Chinese couples revealed rarer mutations at -29 and an ATG-AGG base substitution at the initiation codon for translation. In the Malay couples, genomic sequencing detected mutations at codon 15 (TGG-TAG) and codon 26 (GAG-AAG). We conclude that ARMS with its direct detection of amplified products by gel electrophoresis provides an accurate, rapid, and simpler method for our beta-thalassaemia prenatal diagnosis programme in Singapore. PMID- 7877958 TI - Measurement of fetal urine production in mild infantile polycystic kidney disease -a case report. AB - It is generally recognized that the sonographic findings of infantile polycystic kidney disease (IPKD) are bilaterally enlarged kidneys, oligohydramnios, an absent fetal bladder, and the typical kidney texture. Since there is a broad spectrum of renal compromise with IPKD, in utero diagnosis is thought to be limited to the severe forms. This paper reports a mild case of IPKD, where the in utero diagnosis was established by measuring fetal urine production and amniotic fluid volume serially during pregnancy, and by ultrasonographic examination of fetal kidneys. PMID- 7877959 TI - Prenatal diagnosis of renal agenesis in a twin gestation. AB - Bilateral renal agenesis is a lethal congenital anomaly. It appears to be transmitted in a polygenic pattern. The prenatal ultrasound findings consist of severe oligohydramnios, absence of the fetal bladder, and failure to identify fetal kidneys. Twin gestations with renal agenesis have been described in the paediatric literature. We detail a case of a patient with two prior affected pregnancies with bilateral renal agenesis. Her latest pregnancy was diagnosed prenatally, with one fetus with bilateral and the other fetus with unilateral renal agenesis. The ultrasound findings should be differentiated from the stuck twin phenomenon. PMID- 7877960 TI - The 18ph+ chromosome heteromorphism. PMID- 7877961 TI - Prenatal diagnosis of partial 2p trisomy by 'de novo' duplication 2p (13.1-->21). Confirmation by FISH. PMID- 7877962 TI - On the inheritance of Harlequin ichthyosis. PMID- 7877963 TI - Amyotrophic lateral sclerosis: human challenge for neuroscience. PMID- 7877964 TI - Kinetic and affinity limits on antibodies produced during immune responses. PMID- 7877966 TI - Transport of proteins dissolved in organic solvents across biomimetic membranes. AB - Using lipid-impregnated porous cellulose membranes as biomimetic barriers, we tested the hypothesis that to afford effective transmembrane transfer of proteins and nucleic acids, the vehicle solvent should be able to dissolve both the biopolymers and the lipids. While the majority of solvents dissolve one or the other, ethanol and methanol were found to dissolve both, especially if the protein had been lyophilized from an aqueous solution of a pH remote from the protein's isoelectric point. A number of proteins, as well as RNA and DNA, dissolved in these alcohols readily crossed the lipidized membranes, whereas the same biopolymers placed in nondissolving solvents (e.g., hexane and ethyl acetate) or in those unable to dissolve lipids (e.g., water and dimethyl sulfoxide) exhibited little transmembrane transport. The solubility of biopolymers in ethanol and methanol was further enhanced by complexation with detergents and poly(ethylene glycol); significant protein and nucleic acid transport through the lipidized membranes was observed from these solvents but not from water. PMID- 7877965 TI - Early high-affinity neutralizing anti-viral IgG responses without further overall improvements of affinity. AB - Affinity maturation of IgG antibodies in adaptive immune responses is a well accepted mechanism to improve effector functions of IgG within 2 weeks to several months of antigen encounter. This concept has been defined mainly for IgG responses against chemically defined haptens. We have evaluated this concept in a viral system and analyzed neutralizing IgG antibody responses against vesicular stomatitis virus (a close relative of rabies virus) with a panel of monoclonal antibodies obtained early (day 6 or 12) and late (day 150) after hyperimmunization. These neutralizing IgG antibodies recognize a single major antigenic site with high affinities (Ka of 10(8)-10(10) liter.mol-1) and with rapid on-rates already on day 6 of a primary response and with no evidence for further antigen dose- and time-dependent overall improvement of affinity. This type of IgG response is probably representative for viruses or bacterial toxins which are crucially controlled by neutralizing antibodies. PMID- 7877967 TI - Biological and structural characterization of a Ras transforming mutation at the phenylalanine-156 residue, which is conserved in all members of the Ras superfamily. AB - Although Ras residue phenylalanine-156 (F156) is strictly conserved in all members of the Ras superfamily of proteins, it is located outside of the consensus GDP/GTP-binding pocket. Its location within the hydrophobic core of Ras suggests that its strict conservation reflects a crucial role in structural stability. However, mutation of the equivalent residue (F157L) in the Drosophila Ras-related protein Rap results in a gain-of-function phenotype, suggesting an alternative role for this residue. Therefore, we have introduced an F156L mutation into Ras to evaluate the role of this residue in Ras structure and function. Whereas introduction of this mutation activated the transforming potential of wild-type Ras, it did not impair that of oncogenic Ras. Further, Ras (156L) exhibited an extremely rapid off rate for bound GDP/GTP in vitro and showed increased levels of Ras.GTP in vivo. To determine the structural basis for these altered properties, we used high-resolution nuclear magnetic resonance spectroscopy. The F156L mutation caused loss of contact with residues 6, 23, 55, and 79, resulting in disruption of secondary structure in alpha-helix 1 and in beta-sheets 1-5. These major structural changes contrast with the isolated alterations induced by oncogenic mutation (residues 12 or 61) that perturb GTPase activity, and instead, weaken Ras contacts with Mg2+ and its guanine nucleotide substrate and result in increased rates of GDP/GTP dissociation. Altogether, these observations demonstrate the essential role of this conserved residue in Ras structure and its function as a regulated GDP/GTP switch. PMID- 7877968 TI - Evolution-like selection of fast-folding model proteins. AB - We propose an algorithm providing sequences of model proteins with rapid folding into a given target (native) conformation. This algorithm is applied to a chain of 27 residues on a cubic lattice. It generates sequences with folding 2 orders of magnitude faster than that of the practically random starting sequence. Thermodynamic analysis shows that the increase in speed is matched by an increase in stability: the evolved sequences are much more stable in their native conformation than the initial random sequence. The unfolding temperature for evolved sequences is slightly higher than the simulation temperature, bearing direct correspondence to the relatively low stability of real proteins. PMID- 7877969 TI - Yeast glycosylation mutants are sensitive to aminoglycosides. AB - Aminoglycosides are a therapeutically important class of antibiotics that inhibit bacterial protein synthesis and a number of viral and eukaryotic functions by blocking RNA-protein interactions. Vanadate-resistant Saccharomyces cerevisiae mutants with defects in Golgi-specific glycosylation processes exhibit growth sensitivity to hygromycin B, an aminoglycoside [Ballou, L., Hitzeman, R. A., Lewis, M. S. & Ballou, C. E. (1991) Proc. Natl. Acad. Sci. USA 88, 3209-3212]. Here, evidence is presented that glycosylation is, in and of itself, a key factor mediating aminoglycoside sensitivity in yeast. Examination of mutants with a wide range of glycosylation abnormalities reveals that all are sensitive to aminoglycosides. This effect is specific to aminoglycosides and not merely a consequence of increased permeability of the yeast mutants to drugs. Furthermore, inhibition of glycosylation in wild-type cells leads to a marked increase in their sensitivity to aminoglycosides. These results establish that a defect in glycosylation is sufficient to render yeast cells susceptible to these clinically important drugs. Further, they suggest that a molecule which prevents the uptake or mediates removal of aminoglycosides requires glycosylation for its activity. Perhaps more importantly, this finding on drug sensitivity provides the most powerful screen to date to identify mutants and thereby to isolate genes involved in all aspects of N-linked glycosylation. PMID- 7877970 TI - Maintenance of an extrachromosomal plasmid vector in mouse embryonic stem cells. AB - We have constructed and characterized a polyoma virus-based plasmid that is maintained as an autonomously replicating extrachromosomal element (episome) in mouse embryonic stem (ES) cells. Plasmid pMGD20neo contains the polyoma origin of replication harboring a mutated enhancer (PyF101), a modified polyoma early region that encodes the large tumor (T) antigen only, and a gene that confers resistance to G418 (neo). After transfection, the plasmid replicates in ES cells and is maintained as an extrachromosomal element in 15% of G418-resistant clones. Integration of the plasmid DNA is undetectable for at least 28 cell generations. In one clone, the transfected DNA persists unaltered as an episome at 10-30 copies per cell for at least 74 cell generations in the presence of G418. Cells that maintain the autonomously replicating plasmid can efficiently replicate and maintain a second plasmid that carries the polyoma origin of replication. Independent vector-containing ES cell lines showed no significant alteration of the karyotype, and two cell lines yielded several chimeric animals when introduced into blastocysts, suggesting that the presence of an episomal element and expression of polyoma large T do not eliminate the ES cells' ability to populate an embryo. This system offers an efficient means for manipulating and analyzing various aspects of gene expression in ES cells. PMID- 7877971 TI - Xenopus Gq alpha subunit activates the phosphatidylinositol pathway in Xenopus oocytes but does not consistently induce oocyte maturation. AB - We cloned the Xenopus laevis form of Gq alpha subunit to study its effects on oocyte maturation. Injection of Xenopus Gq alpha mRNA into stage 6 oocytes activated the phospholipase C/phosphatidylinositol pathway. The oocyte membrane became permeable to calcium ions and was able to generate transient inward currents (T(in)), due to the opening of Ca(2+)-dependent Cl- channels. The T(in) amplitude developed over several hours and disappeared by 24 hr. Diacylglycerol levels were found to parallel the appearance and disappearance of the T(in). The concurrent decline of T(in) values and diacylglycerol was not due to a failure in the synthesis of Gq alpha protein, which was produced continuously for > 24 hr. After Xenopus Gq alpha mRNA injection, germinal vesicle breakdown (GVBD) was variable (0-100%) in stage 6 oocytes, whereas none of the stage 4 oocytes underwent GVBD. In contrast, stage 6 oocytes injected with mRNA encoding the Go alpha G protein consistently underwent GVBD but did not acquire T(in). Our results show that activation of phospholipase C is not an absolute requisite for the induction of maturation, although in oocytes of some frogs phospholipase C activation can trigger a pathway to GVBD. PMID- 7877972 TI - Sexually dimorphic DNA demethylation in the promoter of the Slp (sex-limited protein) gene in mouse liver. AB - Mouse Slp, a duplicate of the fourth complement component (C4) gene, exhibits EDTA-independent complement activity with a hepatic expression that is male specific. To provide an underlying mechanism for the male-specific expression, we have analyzed the promoter activity of the various 5'-flanking sequences and CpG demethylation of the Slp gene. Transient transfections using HepG2 cells indicate that the element TTCCGGGC (nt -124 to -117) regulates the promoter activity. Moreover, CpG at position -121 of this regulatory element is demethylated to a much higher degree in males than in females. This sexually dimorphic DNA demethylation is consistent with the male-specific expression of the Slp gene in DBA/2 males. The regulatory element binds to the different TTCCGGGC-specific nuclear proteins depending on the methylation of the CpG site. In contrast, the corresponding CpG at position -119 of the C4 gene, which is expressed in both males and females, is demethylated at equal and high levels in both sexes. We therefore propose that the DNA demethylation and methylation-sensitive transcription factors may be a part of the regulatory mechanism for the male specific expression of the Slp gene. PMID- 7877973 TI - Intracellular interleukin 6 mediates platelet-derived growth factor-induced proliferation of nontransformed cells. AB - The functional relevance of interleukin 6 (IL-6) in platelet-derived growth factor (PDGF)-induced cell growth was evaluated in cultures of human fibroblasts, vascular smooth muscle cells, and mesangial cells. The three isoforms of the PDGF -namely, PDGF-AA, -AB, and -BB--induced the expression of the IL-6 gene and proliferation of the nontransformed cells. PDGF-induced transcription, translation, and secretion of IL-6 were diminished in the presence of IL-6 antisense oligonucleotides. While neutralizing anti-IL-6 antibodies failed to affect the growth factor-dependent cell proliferation, IL-6 antisense oligonucleotides inhibited cell division. In addition, IL-6 antisense oligonucleotides abolished PDGF-induced transcription of the genes coding for the cell division cycle 2-related protein (CDC2) and proliferating cell nuclear antigen (PCNA), both of which are regulated in a cell cycle-dependent manner. It is concluded that PDGF-dependent proliferation of nontransformed cells involves the action of intracellular IL-6. PMID- 7877974 TI - Real time imaging of transcriptional activity in live mouse preimplantation embryos using a secreted luciferase. AB - Study of gene expression kinetics during preimplantation mammalian development is difficult because of the limited amount of material and the usually destructive, static nature of molecular analyses. We describe continuous, noninvasive monitoring of gene expression in preimplantation embryos by using a secreted luminescent reporter, Vargula luciferase. Transgene expression profiles were followed by assaying aliquots of culture medium or by direct visualization of Vargula luciferase secretion from living embryos in real time through photon imaging. With this approach, it is possible to observe epigenetic modulations of gene expression and to link this over time to the developmental capacity of individual embryos. In addition, by developing a strategy where expression from integrated transgenes is enhanced relative to that from nonintegrated DNA, we provide evidence that rapid detection of transgene integration prior to the blastocyst stage should be possible. Thus, imaging of Vargula luciferase secretion may also be useful in the early screening of embryos, for example, in the production of transgenic livestock. PMID- 7877975 TI - Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors. AB - Hypersecretion of luteinizing hormone (LH) is implicated in infertility and miscarriages in women. A lack of animal models has limited progress in determining the mechanisms of LH toxicity. We have recently generated transgenic mice expressing a chimeric LH beta subunit (LH beta) in gonadotropes. The LH beta chimera contains the C-terminal peptide of the human chorionic gonadotropin beta subunit. Addition of this peptide to bovine LH beta resulted in a hormone with a longer half-life. Furthermore, targeted expression of the LH beta chimera led to elevated LH levels and infertility in female transgenics. These mice ovulated infrequently, maintained a prolonged luteal phase, and developed pathologic ovarian changes such as cyst formation, marked enlargement of ovaries, and granulosa cell tumors. Testosterone and estradiol levels were increased compared to nontransgenic littermates. An unusual extragonadal phenotype was also observed: transgenic females developed hydronephropathy and pyelonephritis. The pathology observed demonstrates a direct association between abnormal secretion of LH and infertility and underscores the utility of the transgenic model for studying how excess LH leads to cyst formation, ovarian tumorigenesis, and infertility. PMID- 7877976 TI - Development of anti-p185HER2 immunoliposomes for cancer therapy. AB - The product of the HER2 protooncogene, p185HER2, represents an attractive target for cancer immunotherapies. We have prepared anti-p185HER2 immunoliposomes in which Fab' fragments of a humanized anti-p185HER2 monoclonal antibody with antiproliferative properties (rhuMAb-HER2) were conjugated to either conventional or sterically stabilized liposomes. These immunoliposomes bind specifically to p185HER2-overexpressing breast cancer cells (SK-BR-3 and BT-474). High-affinity binding of anti-p185HER2 immunoliposomes is comparable to that of free rhuMAbHER2 Fab' or the intact antibody. Empty immunoliposomes inhibit the culture growth of p185HER2-overexpressing breast cancer cells, and this antiproliferative effect is superior to that of free rhuMAbHER2-Fab', indicating that liposomal anchoring of these anti-p185HER2 Fab' fragments enhances their biological activity. Efficient internalization of anti-p185HER2 immunoliposomes, demonstrated by light and electron microscopy, occurs by receptor-mediated endocytosis via the coated pit pathway and also possibly by membrane fusion. Doxorubicin-loaded anti-p185HER2 immunoliposomes are markedly and specifically cytotoxic against p185HER2 overexpressing tumor cells in vitro. Anti-p185HER2 immunoliposomes administered in vivo in Scid mice bearing human breast tumor (BT-474) xenografts can deliver doxorubicin to tumors. These results indicate that anti-p185HER2 immunoliposomes are a promising therapeutic vehicle for the treatment of p185HER2-overexpressing human cancers. PMID- 7877977 TI - Evidence that carcinogenesis involves an imbalance between epigenetic high frequency initiation and suppression of promotion. AB - Evidence is presented in support of the hypothesis that cancer development depends on an imbalance between highly frequent epigenetic initiation and suppression of promotion of the initiated cells. When irradiated clonogenic mammary epithelial cells are transplanted and hormonally stimulated, they give rise to clonal glandular structures within which carcinomas may arise. In the current study, the cancer incidence in grafts of approximately 13 7-Gy-irradiated clonogens per site indicated that at least 1 of approximately 95 clonogens was radiogenically initiated. A similar initiation frequency had been seen in grafts of approximately 5 methylnitrosourea (MNU)-treated clonogens. Such initiation is thus far more frequent than specific locus mutations. In sites grafted with larger cell inocula, cancer incidences per clonogen were suppressed inversely as the numbers of irradiated or MNU-treated clonogens per graft increased. Addition of unirradiated cells to small irradiated graft inocula also suppressed progression. Radiation and MNU thus produce quantitatively, and perhaps qualitatively, similar carcinogenesis-related sequelae in mammary clonogens. PMID- 7877978 TI - Leukemia inhibitory factor protects against experimental lethal Escherichia coli septic shock in mice. AB - Leukemia inhibitory factor (LIF) has recently been associated with septic shock in humans. In this study we sought to determine, in mice, the role of LIF in septic shock. During sublethal endotoxemia, serum LIF levels, as determined by radio-receptor competition assay, peaked at 2 h and were low (3 ng/ml), whereas in lethal Escherichia coli septic shock serum LIF levels rose progressively (> 30 ng/ml) in the premorbid phase coincident with the development of tissue injury. Single i.v. injections of high doses (up to 50 micrograms per mouse) of recombinant murine LIF had no obvious acute detrimental effects, whereas continued i.p. administration (30 micrograms per mouse per day) for 3-4 days induced a fatal catabolic state without evidence of preceding hemodynamic collapse or shock. Simultaneous or subsequent administration of high doses of LIF had no effect on mortality from sublethal and lethal E. coli septic shock, whereas prior administration conferred significant protection against lethality (P << 0.001 by log-rank test), an effect that was dose and interval dependent. This protective effect resembled endotoxin tolerance and was characterized by suppression of E. coli-induced serum tumor necrosis factor concentration (P < 0.05), reduction in the number of viable bacteria (P < 0.05), and prevention of sepsis-induced tissue injury. These observations suggest that systemic LIF production is part of the host response to both endotoxin and sepsis-induced tissue injury. PMID- 7877979 TI - p53-mediated cellular response to DNA damage in cells with replicative hepatitis B virus. AB - Wild-type p53 acts as a tumor suppressor gene by protecting cells from deleterious effects of genotoxic agents through the induction of a G1/S arrest or apoptosis as a response to DNA damage. Transforming proteins of several oncogenic DNA viruses inactivate tumor suppressor activity of p53 by blocking this cellular response. To test whether hepatitis B virus displays a similar effect, we studied the p53-mediated cellular response to DNA damage in 2215 hepatoma cells with replicative hepatitis B virus. We demonstrate that hepatitis B virus replication does not interfere with known cellular functions of p53 protein. PMID- 7877980 TI - Retinoblastoma gene product as a downstream target for a ceramide-dependent pathway of growth arrest. AB - Ceramide, a lipid mediator, has been most closely associated with antiproliferative activities. In this study, we examine the mechanism by which ceramide induces growth suppression and the role of the retinoblastoma gene product (Rb) in this process. Withdrawal of serum from the serum-dependent MOLT-4 cells resulted in significant dephosphorylation of Rb, correlating with the induction of G0/G1 cell cycle arrest. Serum withdrawal resulted in marked elevation in the levels of endogenous ceramide (3-fold at 24 h and 8-fold at 96 h) with little changes in the endogenous levels of sphingosine. The addition of exogenous C6-ceramide resulted in a concentration- and time-dependent dephosphorylation of Rb. Exogenous ceramide was active at levels comparable to endogenous levels achieved with serum withdrawal. Peak activity of exogenous ceramide (at 6 h) correlated with the uptake of C6-ceramide by MOLT-4 cells. Next, a number of studies were conducted to determine whether Rb plays a role in ceramide-induced growth suppression. (i) C6-Ceramide was poorly active in growth suppression of retinoblastoma cells that lack Rb. (ii) Mink lung epithelial cells in which Rb had been sequestered by overexpression of large tumor antigen were resistant to the action of ceramide compared to cells transfected with large tumor antigen mutated in the Rb-binding pocket. (iii) Overexpression of the EIA adenoviral protein, which binds and sequesters Rb, resulted in protection from growth suppression and cell cycle arrest induced by ceramide. Thus, these studies demonstrate that Rb is a downstream target for ceramide and may function in a growth suppressor pathway resulting in cell cycle arrest. PMID- 7877981 TI - The dif resolvase locus of the Escherichia coli chromosome can be replaced by a 33-bp sequence, but function depends on location. AB - The dif locus (deletion-induced filamentation) of Escherichia coli is a resolvase site, located in the terminus region of the chromosome, that reduces chromosome multimers to monomers. In strains in which this site has been deleted, a fraction of the cells is filamentous, has abnormal nucleoid structure, and exhibits elevated levels of the SOS repair system. We have demonstrated that a 33-bp sequence, which is sufficient for RecA-independent recombination and which shows similarity to the cer site of pColE1, suppresses the Dif phenotype when inserted in the terminus region. Flanking sequences were not required, since suppression occurred in strains in which dif as well as 12 kb or 173 kb of DNA had been deleted. However, location was important, and insertions at a site 118 kb away from the normal site did not suppress the Dif phenotype. These sites were otherwise still functional, and they exhibited wild-type levels of RecA independent recombination with dif-containing plasmids and recombined with other chromosomal dif sites to cause deletions and inversions. It is proposed that the functions expressed by a dif site depend on chromosome location and structure, and analysis of these functions provides a way to examine the structure of the terminus region. PMID- 7877983 TI - The U3 promoter region of the acutely lethal simian immunodeficiency virus clone smmPBj1.9 confers related biological activity on the apathogenic clone agm3mc. AB - Infection with the acutely pathogenic molecular virus clone SIVsmmPBj1.9, cloned from isolate PBj14 of simian immunodeficiency virus (SIV) from sooty mangabey monkeys (Cercocebus atys), leads to acute viral and often lethal disease within days or weeks. SIVsmmPBj1.9 has the unique property of replicating in nonstimulated peripheral blood mononuclear cells from pig-tailed macaques. In contrast, molecular virus clone SIVagm3mc of SIV from African green monkeys (Cercopithecus aethiops), which is apathogenic in its natural host and in pig tailed macaques, is unable to grow in nonstimulated peripheral blood cells. Chimeric proviruses were constructed by exchanging defined regions of SIVagm3mc against comparable regions of SIVsmmPBj1.9. Four of five hybrid viruses generated by transfection into the CD4-positive T-cell line C8166 replicated in T-cell lines permissive for SIVagm3mc replication and in stimulated peripheral blood cells from pig-tailed macaques and from African green monkeys. Three hybrid viruses displayed the distinct biological property of SIVsmmPBj14 to replicate in nonstimulated peripheral blood cells from pig-tailed macaques and from African green monkeys. Replication in nonstimulated peripheral blood cells was dependent on the presence of the U3 promoter region of SIVsmmPBj1.9 within the viral long terminal repeat. PMID- 7877984 TI - Selective boron delivery to murine tumors by lipophilic species incorporated in the membranes of unilamellar liposomes. AB - The nido-carborane species K[nido-7-CH3(CH2)15-7,8-C2B9H11] has been synthesized for use as an addend for the bilayer membrane of liposomes. Small unilamellar vesicles, composed of distearoylphosphatidylcholine/cholesterol, 1:1, and incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer, have been investigated in vivo. The time-course biodistribution of boron delivered by these liposomes was determined by inductively coupled plasma-atomic emission spectroscopy analyses after the injection of liposomal suspensions in BALB/c mice bearing EMT6 mammary adenocarcinomas. At the low injected doses normally used (approximately 5-10 mg of boron per kg of body weight), peak tumor boron concentrations of approximately 35 micrograms of boron per g of tissue and tumor/blood boron ratios of approximately 8 were achieved. These values are sufficiently high for the successful application of boron neutron capture therapy. The bilayer-embedded boron compound may provide the sole boron source or, alternatively, a concentrated aqueous solution of a hydrophilic boron compound may also be encapsulated within the liposomes to provide a dose enhancement. Thus, the incorporation of both K[nido-7-CH3(CH2)15-7,8-C2B9H11] and the hydrophilic species, Na3[1-(2'-B10H9)-2-NH3B10H8], within the same liposomes demonstrated significantly enhanced biodistribution characteristics, exemplified by maximum tumor boron concentrations of approximately 50 micrograms of boron per g of tissue and tumor/blood boron ratios of approximately 6. PMID- 7877982 TI - Multiple members of the E2F transcription factor family are the products of oncogenes. AB - The retinoblastoma gene product (pRB) is a known tumor suppressor, capable of arresting growth in mid-to-late G1. Part of its growth suppression action arises from interaction(s) with one or more members of the E2F family of transcription factors. These proteins most likely contribute to progression from G0 to S phase in mammalian cells, and pRB binding most likely inhibits aspects of their suspected growth-promoting function. Given their growth-stimulating potential, we asked whether one or more E2F alleles can function as oncogenes. Uncloned pools of NIH 3T3 cells producing the pRB binding target E2F-1, E2F-2, or E2F-3 grew in semisolid medium. In addition, they grew to much higher saturation density than controls. From the study of cells producing selected E2F-1 mutant species, it appears that E2F DNA-binding function contributes to, and pRB/E2F binding suppresses, soft-agar growth. Thus, three E2F family members can act as oncogene products, suggesting that part of the normal role of pRB is to down-modulate this potential activity. PMID- 7877985 TI - An early increase in somatostatin mRNA expression in the frontal cortex of rhesus monkeys infected with simian immunodeficiency virus. AB - Motor and cognitive impairment is common in human immunodeficiency virus disease in humans and simian immunodeficiency virus (SIV) disease in rhesus monkeys. We have examined peptide neurotransmitter expression in the frontal cortex of SIV infected rhesus monkeys to identify alterations in cortical neurons that might explain this impairment. A 2-fold higher number of preprosomatostatin (SRIF) mRNA positive interneurons was observed in layer IV of frontal cortex in two separate cohorts of SIV-infected animals compared to uninfected controls. Increased SRIF mRNA expression in layer IV was independent of clinical signs of immunodeficiency disease and was associated with both motor and cognitive impairment. Altered SRIF mRNA expression in deeper cortical layers was associated specifically with motor impairment. Increased SRIF mRNA expression occurred without detectable changes in cortical cell density. These data suggest two mechanisms for cortical dysfunction associated with lentivirus infection. Increased SRIF mRNA expression in layer IV may be due to altered patterns of activity in cortical afferents that project to layer IV, while increased SRIF mRNA expression in deeper cortical layers could reflect susceptibility to locally generated mediators in response to primate lentivirus infection of the brain. Altered function of somatostatinergic interneurons may contribute to primate lentivirus-induced encephalopathy. PMID- 7877987 TI - Reduction of caveolin and caveolae in oncogenically transformed cells. AB - Caveolae are flask-shaped non-clathrin-coated invaginations of the plasma membrane. In addition to the demonstrated roles for caveolae in potocytosis and transcytosis, caveolae may regulate the transduction of signals from the plasma membrane. Transformation of NIH 3T3 cells by various oncogenes leads to reductions in cellular levels of caveolin, a principal component of the protein coat of caveolae. The reduction in caveolin correlates very well with the size of colonies formed by these transformed cells when grown in soft agar. Electron microscopy reveals that caveolae are morphologically absent from these transformed cell lines. These observations suggest that functional alterations in caveolae may play a critical role in oncogenic transformation, perhaps by disrupting contact inhibition in transformed cells. PMID- 7877986 TI - Identification of a Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in non-N-methyl-D-aspartate glutamate receptors. AB - Glutamate receptor ion channels are colocalized in postsynaptic densities with Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II), which can phosphorylate and strongly enhance non-N-methyl-D-aspartate (NMDA) glutamate receptor current. In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. A synthetic peptide corresponding to residues 620-638 in GluR1 was phosphorylated in vitro by CaM kinase II but not by cAMP-dependent protein kinase or protein kinase C. The 32P labeled peptide map of this synthetic peptide appears to be the same as the two dimensional peptide map of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) glutamate receptors phosphorylated in cultured hippocampal neurons by CaM kinase II described elsewhere. This CaM-kinase II regulatory phosphorylation site is conserved in all AMPA/kainate-type glutamate receptors, and its phosphorylation may be important in enhancing postsynaptic responsiveness as occurs during synaptic plasticity. PMID- 7877988 TI - A diabetes-associated T-cell autoantigen maps to a telomeric locus on mouse chromosome 6. AB - Identification of diabetes-associated T-cell autoantigens is important for understanding the immunopathology of diabetes and developing improved therapeutic strategies. We have used a genetic approach to move toward identifying the autoantigen recognized by a diabetogenic islet-specific T-cell clone from a nonobese diabetic (NOD) mouse. The unique antigen recognition pattern of this clone was utilized to map the gene encoding the antigen (or its expression) by genetic linkage analysis. In vitro analysis of T-cell proliferation by this clone showed that the capacity of the islets to stimulate T cells segregates as a single codominant gene in BALB/cByJ x (BALB/cByJ x NOD/Bdc) backcross mice. This phenotype was tightly linked to two microsatellites in the telomeric region of mouse chromosome 6. PMID- 7877989 TI - Recognition of oxidatively damaged and apoptotic cells by an oxidized low density lipoprotein receptor on mouse peritoneal macrophages: role of membrane phosphatidylserine. AB - We recently reported that oxidized low density lipoprotein (OxLDL), but not acetyl LDL (AcLDL), inhibited the binding and phagocytosis of nonopsonized, oxidatively damaged red blood cells (OxRBCs) by mouse peritoneal macrophages, implying the involvement of a "scavenger receptor" other than the AcLDL receptor. Numerous studies establish that loss of plasma membrane phospholipid asymmetry, which increases phosphatidylserine expression on the outer leaflet of the membrane, can play a key role in macrophage recognition of damaged and apoptotic cells. We report here that this recognition is in part attributable to the same mouse macrophage receptor that recognizes OxLDL. As described in an accompanying paper, this is a plasma membrane protein of 94-97 kDa. Phosphatidylserine liposomes show strong ligand binding to the same 94- to 97-kDa protein and this binding is inhibited by OxLDL but not by AcLDL. Inhibition of the RBC membrane phospholipid translocase by incubation with sodium vanadate caused a progressive increase in the appearance of phosphatidylserine on the cell surface and a parallel increase in the binding of these RBCs to macrophages, binding that was inhibited by OxLDL. Finally, OxLDL also inhibited the binding of sickled RBCs and apoptotic thymocytes to mouse macrophages. However, the latter was incomplete (approximately 50%), suggesting that other receptors are also involved. We suggest that the OxLDL receptor plays a significant role in recognition of damaged and apoptotic cells. PMID- 7877990 TI - Cellular and humoral immune responses to adenoviral vectors containing factor IX gene: tolerization of factor IX and vector antigens allows for long-term expression. AB - Recombinant adenoviruses containing the canine factor IX (FIX) cDNA were directly introduced in the hind leg muscle of mice. We show that (i) in nude mice, high expression (1-5 micrograms/ml in plasma) of FIX protein can be detected for > 300 days; (ii) in contrast, expression of FIX protein was transient (7-10 days) in normal mice; (iii) CD8+ lymphocytes could be detected within 3 days in the infected muscle tissue; (iv) use of beta 2-microglobulin and immunoglobulin M heavy chain "knockout" mice showed that lack of sustained expression of FIX protein is due to cell-mediated and humoral immune responses; (v) normal mice, once infected with recombinant adenovirus, could not be reinfected efficiently for at least 30 days due to neutralizing viral antibodies; and, finally, (vi) using immunosuppressive drugs, some normal mice can be tolerized to produce and secrete FIX protein for > 5 months. We conclude that currently available adenoviral vectors have serious limitations for use for long-term gene therapy. PMID- 7877991 TI - Protein kinase C epsilon is localized to the Golgi via its zinc-finger domain and modulates Golgi function. AB - Protein kinase C (PKC) is a multigene family of serine/threonine kinases that are central to many signal transduction pathways. Among the PKC isozymes, only PKC epsilon has been reported to exhibit full oncogenic potential. PKC epsilon also displays unique substrate specificity and intracellular localization. To examine the interrelationship between the biological effects and domain structure of PKC epsilon, NIH 3T3 cells were stably transfected to overexpress different epitope tagged fragments of PKC epsilon. The overexpressed proteins each contain the epsilon-tag peptide at the C terminus to allow ready detection with an antibody specific for the tag. The holo-PKC epsilon was found to localize with the Golgi network and other compartments, whereas the zinc-finger domain localized exclusively at the Golgi. Golgi-specific glycosaminoglycan sulfation was strongly inhibited in cells overexpressing either holo-PKC epsilon or its zinc-finger domain, while the secretion of sulfated glycosaminoglycans into the medium was impaired in cells expressing the PKC epsilon zinc-finger domain. Thus, these results suggest that PKC epsilon may be involved in specifically regulating Golgi related processes. Further, the results indicate that PKC epsilon domains other than the kinase domain may also have biological activity and that the zinc-finger domain may function as a subcellular localization signal. PMID- 7877993 TI - Apoptosis and interleukin 7 gene expression in chronic B-lymphocytic leukemia cells. AB - mRNA for interleukin 7 (IL-7) was readily detected in leukemic cells immediately upon their removal from patients with chronic B-lymphocytic leukemia (B-CLL). IL 7 mRNA expression and IL-7 gene transcription were down regulated, however, when B-CLL cells were placed in culture at 37 degrees C for 4 hr. Down regulation of the IL-7 gene was prevented in cells maintained at 4 degrees C. Continued culture of B-CLL cells at 37 degrees C resulted in programmed cell death, or apoptosis, as evidenced by DNA fragmentation. The coincident kinetics of IL-7 gene down regulation and apoptosis suggested that IL-7 gene expression may be required for maintenance of CLL viability in vivo. Signals for IL-7 gene regulation and apoptosis induction were thus examined. Activation of normal B cells through their immunoglobulin receptors did not result in upregulation of IL-7 gene expression. Reagents required for CLL cell purification and culture also did not contribute to IL-7 gene regulation and apoptosis induction. IL-7 gene expression was retained and apoptosis was prevented, however, in CLL cells cultured on a monolayer of EA.hy926 human umbilical cord endothelial hybrid cells. Signals specifically presented by EA.hy926 cells supported both CLL cell viability and IL 7 gene expression, whereas culture of CLL cells on A549/8 carcinoma cells, the fusion partner used to generate the EA.hy926 cells, did not. Cell-cell contact was required, as culture supernatants did not prevent apoptosis. Specifically, IL 7 mRNA expression was retained and apoptosis was prevented only by contact with the endothelial cell hybrids. Preliminary data indicated that integrins expressed on CLL cells affected modulation of apoptosis and IL-7 gene regulation, suggesting that integrins may play significant roles in regulating viability of CLL cells. PMID- 7877992 TI - Comparison of genetically engineered herpes simplex viruses for the treatment of brain tumors in a scid mouse model of human malignant glioma. AB - Genetically engineered viruses and viral genes inserted into retroviral vectors are increasingly being considered for experimental therapy of brain tumors. A primary target of these viruses and vectors is human gliomas, the most frequently occurring primary human brain tumor. To investigate the potential of genetically engineered herpes simplex viruses (HSVs) in the therapy of these tumors, we compared the attributes of two viruses, a recombinant from which the gamma 1(34.5) gene had been deleted (R3616) and a recombinant in which the gamma 1(34.5) gene had been interrupted by a stop codon (R4009). Previous studies have shown that these recombinants were completely devoid of the ability to multiply in the central nervous system of rodents. To pursue these studies, we developed a scid mouse glioma model. Tumor cell response (survival) for 10(3), 10(4), and 10(5) implanted MT539MG glioma cells was 38, 23, and 15 days, respectively. The results were as follows: (i) both R3616 and R4009 replicate and cause cytolysis in diverse glioma cell lines of murine and human origin in vitro, and (ii) Winn type assays 10(5) MT539MG cells coinoculated with R3616 or R4009 as compared to saline significantly prolonged survival in a dose-dependent fashion. Mice that received only tumor cells or the wild-type parent strain of the recombinants, HSV 1(F), died within 15 days. Survival was greatest with R4009. These experiments define both a model for screening oncolytic viruses and a genetically engineered virus of significant potential use as an oncolytic agent. PMID- 7877994 TI - Direct interaction and N-terminal phosphorylation of c-Jun by c-Mil/Raf. AB - c-Mil is the avian homologue of the mammalian serine/threonine kinase c-Raf-1. c Mil/Raf is a mediator of signal transduction leading to gene expression via the c Jun DNA-binding site, AP-1. Here we show that c-Mil immunopurified from MC29 virus-transformed quail fibroblasts phosphorylates c-Jun in vitro near its N terminus (Ser-63 and -73). Furthermore, the viral oncogene product Gag-Mil of the avian wild-type retrovirus MH2 phosphorylates c-Jun in vitro. A contribution by other known kinases phosphorylating c-Jun, such as the mitogen-activated protein kinases (MAPKs) and the c-Jun N-terminal kinases, was excluded by control reactions. c-Raf-1 and c-Jun directly interact in vitro as shown by various immobilized glutathione S-transferase-Raf fusion proteins which specify the cysteine-rich region of c-Mil/Raf as the major N-terminal binding site. An additional minor binding site is located in the C-terminal region. The biological relevance of these results is demonstrated by coimmunoprecipitation of c-Jun and c-Mil from 32P-labeled MC29- and MH2-transformed fibroblasts as well as normal quail embryo fibroblasts, whereby c-Jun was identified by tryptic phosphopeptide analysis. The complexed c-Jun exhibits a decreased electrophoretic mobility corresponding to a more highly phosphorylated state. Cell fractionation analyses indicate that the c-Mil/c-Jun complex is located in the cytoplasm. The data demonstrate that c-Jun can be a direct target of the protein kinase c-Mil/Raf, suggesting an alternative pathway, which leads to c-Jun phosphorylation independent of the MAPKs and MAPK-related proteins. PMID- 7877995 TI - Plasma albumin is a potent trigger of calcium signals and DNA synthesis in astrocytes. AB - Cells in the central nervous system are normally prevented from coming into contact with albumin and other protein components of blood by the existence of a tight blood-brain barrier. Astrocytes and other glial cells proliferate to form glial scars when the blood-brain barrier is breached. In this report we show that albumin is an important blood component responsible for inducing astrocyte proliferation. Albumin also generates maintained trains of calcium spikes in astrocytes. Neither activity depends on blood coagulation, as albumins from both serum and plasma are approximately equally effective. Methanol extraction of albumin abolishes both actions, and recombination of the methanol-extracted factor with extracted albumin restores full activity indistinguishable from that of native albumin. The factor is sensitive to lipase, and the solvent extraction profile is that of a polar lipid. PMID- 7877996 TI - Axon-induced mitogenesis of human Schwann cells involves heregulin and p185erbB2. AB - The ability of sensory axons to stimulate Schwann cell proliferation by contact was established in the 1970s. Although the mitogen responsible for this proliferation has been localized to the axon surface and biochemically characterized, it has yet to be identified. Recently a family of proteins known as heregulins (HRGs) has been isolated, characterized, and shown to interact with a number of class 1 receptor tyrosine kinases, including the erbB2, erbB3, and erbB4 gene products. These factors include glial growth factor, a Schwann cell mitogen. We have tested the effects of antibodies against components of this system (HRG beta 1 and p185erbB2) in cocultures of rat sensory neurons and human (or rat) Schwann cells to elucidate the role of these proteins in axon-induced Schwann cell proliferation. 2C4, a monoclonal antibody specific for the human p185erbB2 receptor tyrosine kinase, bound to the surface of human Schwann cells and reduced human Schwann cell incorporation of [3H]thymidine by > 90% compared with untreated controls in this coculture system. This antibody had no effect on rat Schwann cell incorporation of [3H]thymidine under similar conditions. A polyclonal antibody raised against HRG beta 1 reduced human and rat Schwann cell incorporation of [3H]thymidine by nearly 80% and up to 49%, respectively, relative to controls. These results imply that a HRG, or a HRG-like molecule, is a component of the axonal mitogen. This mitogen is presented to Schwann cells by axons and induces proliferation through an interaction that involves p185erbB2 on Schwann cells. PMID- 7877997 TI - A mutation in the RCC1-related protein pim1 results in nuclear envelope fragmentation in fission yeast. AB - Members of the RCC1 protein family are chromatin-associated guanine nucleotide exchange factors that have been implicated in diverse cellular processes in various organisms, yet no consensus has been reached as to their primary biological role. The fission yeast Schizosaccharomyces pombe, a single-celled eukaryote, provides an in vivo system in which to study the RCC1/Ran switch by using a temperature-sensitive mutant in the RCC1-related protein pim1. Mitotic entry in the pim1-d1ts mutant is normal, but mitotic exit leads to the accumulation of cells arrested with a medial septum and condensed chromosomes. Although the yeast nuclear envelope normally remains intact throughout the cell cycle, we found a striking fragmentation of the nuclear envelope in the pim1-d1ts mutant following mitosis. This resulted in chromatin that was no longer compartmentalized and an accumulation of pore-containing membranes in the cytoplasm. The development of this terminal phenotype was dependent on the passage of cells through mitosis and was coincident with the loss of viability. We propose that pim1 is required for the reestablishment of nuclear structure following mitosis in fission yeast. PMID- 7877998 TI - Glycinergic synaptic currents in Golgi cells of the rat cerebellum. AB - Recordings were made from Golgi cells in slices from rat cerebellar cortex using whole-cell and outside-out configurations of the patch-clamp technique. Exogenous glycine and gamma-aminobutyric acid (GABA) both activated chloride currents, which could be differentially blocked by strychnine and SR95531, respectively. Inhibitory synaptic currents occurred spontaneously in all Golgi cells. Some were blocked by strychnine while the others were blocked by SR95531. The single channel events occurring during the decay of these two types of inhibitory postsynaptic currents had different amplitudes, which matched the main conductance states of the channels gated by glycine and GABA in outside-out patches. It was concluded that Golgi cells receive both glycinergic and GABAergic synaptic inputs. PMID- 7877999 TI - Bacteriophage T4 MotA and AsiA proteins suffice to direct Escherichia coli RNA polymerase to initiate transcription at T4 middle promoters. AB - Development of bacteriophage T4 in Escherichia coli requires the sequential recognition of three classes of promoters: early, middle, and late. Recognition of middle promoters is known to require the motA gene product, a protein that binds specifically to the "Mot box" located at the -30 region of these promoters. In vivo, the asiA gene product is as critical for middle mode RNA synthesis as is that of the motA gene. In vitro, AsiA protein is known to loosen the sigma 70 core RNA polymerase interactions and to inhibit some sigma 70-dependent transcription, presumably through binding to the sigma 70 subunit. Here we show that, in vitro, purified MotA and AsiA proteins are both necessary and sufficient to activate transcription initiation at T4 middle promoters by the E. coli RNA polymerase in a sigma 70-dependent manner. AsiA is also shown to inhibit recognition of T4 early promoters and may play a pivotal role in the recognition of all three classes of phage promoters. PMID- 7878000 TI - Specific inhibition of herpes simplex virus DNA polymerase by helical peptides corresponding to the subunit interface. AB - The herpes simplex virus DNA polymerase consists of two subunits--a catalytic subunit and an accessory subunit, UL42, that increases processivity. Mutations affecting the extreme C terminus of the catalytic subunit specifically disrupt subunit interactions and ablate virus replication, suggesting that new antiviral drugs could be rationally designed to interfere with polymerase heterodimerization. To aid design, we performed circular dichroism (CD) spectroscopy and analytical ultracentrifugation studies, which revealed that a 36 residue peptide corresponding to the C terminus of the catalytic subunit folds into a monomeric structure with partial alpha-helical character. CD studies of shorter peptides were consistent with a model where two separate regions of alpha helix interact to form a hairpin-like structure. The 36-residue peptide and a shorter peptide corresponding to the C-terminal 18 residues blocked UL42 dependent long-chain DNA synthesis at concentrations that had no effect on synthesis by the catalytic subunit alone or by calf thymus DNA polymerase delta and its processivity factor. These peptides, therefore, represent a class of specific inhibitors of herpes simplex virus DNA polymerase that act by blocking accessory-subunit-dependent synthesis. These peptides or their structures may form the basis for the synthesis of clinically effective drugs. PMID- 7878001 TI - Tension relaxation induced by pulse photolysis of caged ATP in partially crosslinked fibers from rabbit psoas muscle. AB - Muscle contractile force is thought to be generated by ATP-induced conformational changes in myosin crossbridges. In the present study, we investigated the response to ATP binding of force-bearing, attached cross-bridges. For this investigation, skinned fibers, in which myosin heads were in part covalently crosslinked to thin filaments with a zero-length crosslinker, were prepared. Caged ATP [the P3-1-(2-nitro)phenylethyl ester of ATP] was then pulse-photolyzed in these crosslinked fibers, which retained ATP-induced "rigor" tension, and then the subsequent tension changes were followed at 14-16 degrees C and ionic strengths of 0.1-2 M. A rapid tension decrease was observed after the photolysis in the partially crosslinked fibers. The rate of the decrease was not any different from that in the uncrosslinked fibers compared at ionic strength of 0.2 M. This and other results thus indicate a kinetic similarity in the crosslinked and uncrosslinked crossbridges in response to ATP binding. These findings also suggest that ATP-induced structural changes take place in the attached crossbridges at a rate similar to that of the ATP-induced dissociation of crossbridges from thin filaments. PMID- 7878002 TI - Acute hepatitis in rats expressing human hepatitis B virus transgenes. AB - The molecular mechanisms responsible for hepatocyte death and the events leading to viral clearance in hepatitis B virus (HBV) infections are not well understood. Elucidation of the mechanisms involved have been complicated by the difficulty of infecting human hepatocytes with HBV in vitro and the lack of an appropriate animal model. We report an animal model of human HBV infection by in vivo transfection. We have directly introduced a replication-competent, cloned HBV construct into rat liver by using a membrane fusion-promoting cationic lipid. HBV mRNA and 3.2-kb HBV DNA were expressed in the liver by this in vivo transfection method. In the majority of rats, HBV virions and hepatitis B e antigen were found in the blood 3-7 days after transfection, after which antibody to the e antigen appeared. Two to three weeks after the transfection, glutamic-pyruvic transaminase levels were elevated in serum, hepatocyte death and lymphocyte infiltration were observed in the vicinity of the portal vein of liver, and HBV virions were no longer detected in the serum. Thus, transfection of HBV into rats resulted in histological and serological changes comparable to HBV-induced acute hepatitis in humans. In contrast, no hepatocellular injury was observed in T lymphocyte-deficient nude rats transfected with the same HBV construct, and viremia was substantially prolonged, providing direct evidence that T lymphocytes play an essential role in liver cell injury and in the clearance of HBV. This rat hepatitis model will be useful for studying pathogenesis of HBV infection. PMID- 7878003 TI - Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP. AB - Carbon monoxide (CO) is a product of the enzyme heme oxygenase (HO; EC 1.14.99.3). In vascular smooth muscle cells, exogenously administered CO increases cyclic guanosine 3',5'-monophosphate (cGMP), which is an important regulator of vessel tone. We report here that smooth muscle cells produce CO via HO and that it regulates cGMP levels in these cells. Hypoxia, which has profound effects on vessel tone, significantly increased the transcriptional rate of the HO-1 gene resulting in corresponding increases of its mRNA and HO enzymatic activity. In addition, under the same conditions, rat aortic and pulmonary artery smooth muscle cells accumulated high levels of cGMP following a similar time course to that of HO-1 production. The increased accumulation of cGMP in smooth muscle cells required the enzymatic activity of HO, since it was abolished by a specific HO inhibitor, tin protoporphyrin. In contrast, N omega-nitro-L-arginine, a potent inhibitor of nitric oxide (NO) synthesis, had no effect on cGMP produced by smooth muscle cells, indicating that NO is not responsible for the activation of guanylyl cyclase in this setting. Furthermore, conditioned medium from hypoxic smooth muscle cells stimulated cGMP production in recipient cells and this stimulation was completely inhibited by tin protoporphyrin or hemoglobin, an inhibitor of CO production and a scavenger of CO, respectively. This report shows that HO-1 is expressed by vascular smooth muscle cells and that its product, CO, may regulate vascular tone under physiologic and pathophysiologic (such as hypoxic) conditions. PMID- 7878004 TI - Regulation of human retroviral latency by the NF-kappa B/I kappa B family: inhibition of human immunodeficiency virus replication by I kappa B through a Rev dependent mechanism. AB - The cellular transcription factor NF-kappa B stimulates human immunodeficiency virus type 1 (HIV-1) transcriptional initiation, but its role in the retroviral life cycle has not been fully defined. In this report, we show that I kappa B alpha acts as a cellular inhibitor of human retroviral replication through a discrete mechanism, independent of its effect on HIV transcription. I kappa B alpha inhibited HIV replication and gp160 expression by negatively regulating Rev function, most likely acting through a cellular factor involved in Rev transactivation. A similar effect was observed with human T leukemia virus I, in which I kappa B alpha inhibited Rex function. In contrast, no effect was observed on the replication of a DNA virus, adenovirus type 5. The NF-kappa B/I kappa B regulatory pathway therefore modulates human retroviral replication by regulating a program of cellular gene expression required for several steps in the viral life cycle, including not only viral transcription but also RNA export. This interaction between cellular and viral gene products suggests that NF-kappa B plays a broader role in the regulation of human retroviral replication, providing a previously unrecognized link between two important regulators of HIV gene expression and common NF-kappa B-dependent programs of gene expression used by human retroviruses. PMID- 7878005 TI - The Drosophila yolkless gene encodes a vitellogenin receptor belonging to the low density lipoprotein receptor superfamily. AB - Sequence comparisons of vitellogenins from a wide range of organisms have identified regions of similarity not only to each other but also to vertebrate apolipoproteins (e.g. apoB-100 and apoE). Furthermore, the chicken vitellogenin receptor, which also binds apolipoproteins receptor (LDLR) superfamily [Bujo, H., Hermann, M., Kaderli, M. O., Jacobsen, L., Sugawara, S., Nimpf, J., Yamamoto, T. & Schneider, W. J. (1994) EMBO J. 13, 5165-5175]. The yolk proteins of higher dipterans are exceptional, however, and instead show similarity to lipoprotein lipases. The molecular characterization of the putative Drosophila melanogaster vitellogenin receptor gene, yolkless (yl), described in this report reveals that the protein it encodes (Yl), is also a member of the LDLR superfamily. The ovary specific 6.5-kb yl RNA codes for a protein of approximately 210 kDa which contains all three motifs common to the LDLR class of proteins. Within this superfamily, Yl may be related more to the LDLR-related proteins (LRPs), which bind both apolipoproteins and lipoprotein lipases. The similarity of Yl to the other LDLR proteins is restricted to the putative extracellular domain. Most noticeably, the cytoplasmic domain of Yl lacks the typical NPXY sequence which is involved in receptor internalization. PMID- 7878006 TI - A second N-acylhomoserine lactone signal produced by Pseudomonas aeruginosa. AB - Quorum sensing systems are used by a number of Gram-negative bacterial species to regulate specific sets of genes in a cell density-dependent manner. Quorum sensing involves synthesis and detection of extracellular signals termed autoinducers. As shown in recombinant Escherichia coli, the Pseudomonas aeruginosa autoinducer (PAI) N-(3-oxododecanoyl)homoserine lactone, together with the lasR gene product, activate the P. aeruginosa lasB gene. In this study, PAI was shown to activate lasB-lacZ expression in a P. aeruginosa lasR mutant containing a plasmid with lasR under the control of the lac promoter. The concentration of PAI necessary for half-maximal activation of the lasB-lacZ fusion was approximately 1 microM, which is within the range of PAI levels found in P. aeruginosa culture fluids. The effect of PAI on a P. aeruginosa lasR mutant containing a plasmid with lasR under the control of its own promoter and containing the lasB-lacZ fusion was also tested. Although extracts of culture fluid activated the lasB promoter in this construct, concentrations of PAI as high as 10 microM did not. This indicates the presence of a second extracellular factor (factor 2) that is required for lasB activation in P. aeruginosa when lasR is controlled by its own promoter but not when lasR is controlled by a strong foreign promoter. Factor 2 was shown to be N-butyrylhomoserine lactone. Although recombinant E. coli cells containing the PAI synthase gene, lasI, produce PAI, these cells do not produce factor 2. Furthermore, a P. aeruginosa mutant that produced about 0.1% of the wild-type level of PAI made about 5% of the wild-type level of factor 2. This indicates that factor 2 synthesis results from the activity of a gene product other than PAI synthase. The role of factor 2 in virulence gene regulation remains to be determined, but this compound may affect the expression of lasR, which in turn activates transcription of numerous virulence genes in the presence of sufficient PAI. Apparently, multiple quorum sensing systems can occur and interact with each other in a single bacterial species. PMID- 7878007 TI - Expression cloning of the cDNA for a polypeptide associated with rat hepatic sinusoidal reduced glutathione transport: characteristics and comparison with the canalicular transporter. AB - Using the Xenopus oocyte expression system, we previously identified an approximately 4-kb fraction of mRNA from rat liver that expresses sulfobromophthalein reduced glutathione S-conjugate (BSP-GSH)-insensitive and an approximately 2.5-kb fraction expressing BSP-GSH-sensitive reduced glutathione (GSH) transport. From the former, a 4.05-kb cDNA was cloned and characterized as the putative rat canalicular GSH transporter. Starting with a cDNA library constructed from the approximately 2.5-kb fraction, we have now isolated a single clone that leads to expression of a BSP-GSH- and cystathionine-inhibitable GSH transporter activity with Km approximately 3 mM characteristic of the sinusoidal GSH transporter. The cDNA for the rat sinusoidal GSH transporter-associated polypeptide (RsGshT) is 2733 bases with an open reading frame of 1059 nucleotides encoding a polypeptide of 353 amino acids (39,968 Da) with two putative membrane spanning domains. No identifiable homologies were found in searching various data bases. An approximately 40-kDa protein is generated in in vitro translation of cRNA for RsGshT. Northern blot analysis revealed a single approximately 2.8-kb transcript in rat and human liver with negligible hybridization signal in other organs. The abundance of mRNA for RsGshT did not increase with phenobarbital treatment. Cis-inhibition by BSP-GSH and trans-inhibition by cystathionine and lack of induction by phenobarbital are characteristic of sinusoidal GSH secretion and thus indicate that RsGshT either encodes the sinusoidal GSH transporter itself or a regulatory subunit of the transporter that determines its liver specific activity. PMID- 7878008 TI - Functional dissection of circadian clock- and phytochrome-regulated transcription of the Arabidopsis CAB2 gene. AB - Both the circadian clock and phytochrome regulate expression of the Arabidopsis genes encoding the light-harvesting chlorophyll a/b-binding proteins (CAB genes). Phytochrome activates CAB transcription, and it has been proposed that the circadian clock negatively regulates CAB transcription. The tobacco nuclear proteins CUF-1 (CAB upstream factor 1) and CGF-1 (CAB GATA factor 1) bind the Arabidopsis CAB2 promoter, and the CGF-1 binding site is contained within a minimal clock- and phytochrome-regulated region of the promoter. We have used in vivo cab2::luciferase gene bioluminescence markers containing site-directed mutations in the CUF-1 and CGF-1 binding sites to define the role of these proteins in CAB2 regulation and to further delineate the terminal genomic targets of the phytochrome and circadian clock signal transduction pathways. Results from these studies confirm that CUF-1 is not required to generate the circadian clock- or phytochrome-responsive CAB2 expression pattern but rather functions as a positive factor to increase CAB2 expression levels. CGF-1 interaction with the CAB2 promoter mediates the acute increase in CAB2 expression in response to phytochrome activation and contributes to the light-induced high-amplitude circadian oscillation in CAB2 expression. PMID- 7878009 TI - Regulation of leukocyte-endothelium interaction and leukocyte transendothelial migration by intercellular adhesion molecule 1-fibrinogen recognition. AB - Although primarily recognized for its role in hemostasis, fibrinogen is also required for competent inflammatory reactions in vivo. It is now shown that fibrinogen promotes adhesion to and migration across an endothelial monolayer of terminally differentiated myelomonocytic cells. This process does not require chemotactic/haptotactic gradients or cytokine stimulation of the endothelium and is specific for the association of fibrinogen with intercellular adhesion molecule 1 (ICAM-1) on endothelium. Among other adhesive plasma proteins, fibronectin fails to increase the binding of leukocytes to endothelium, or transendothelial migration, whereas vitronectin promotes the binding but not the migration. The fibrinogen-mediated leukocyte adhesion and transendothelial migration could be inhibited by a peptide from the fibrinogen gamma-chain sequence N117NQKIVNL-KEKVAQLEA133, which blocks the binding of fibrinogen to ICAM 1. This interaction could also be inhibited by new anti-ICAM-1 monoclonal antibodies that did not affect the ICAM-1-CD11a/CD18 recognition, thus suggesting that the fibrinogen binding site on ICAM-1 may be structurally distinct from regions previously implicated in leukocyte-endothelium interaction. Therefore, binding of fibrinogen to vascular cell receptors is sufficient to initiate (i) increased leukocyte adhesion to endothelium and (ii) leukocyte transendothelial migration. These two processes are the earliest events of immune inflammatory responses and may also contribute to atherosclerosis. PMID- 7878010 TI - Differential expression of SNAP-25 protein isoforms during divergent vesicle fusion events of neural development. AB - The presynaptic plasma membrane protein SNAP-25 (synaptosome-associated protein of 25 kDa) has been implicated as one of several neural-specific components that direct constitutive fusion mechanisms to the regulated vesicle trafficking and exocytosis of neurotransmitter release. There exist two alternatively spliced isoforms of SNAP-25, a and b, which differ in a putative membrane-interacting domain. We show that these two isoforms have distinct quantitative and anatomical patterns of expression during brain development, in neurons, and in neuroendocrine cells and that the proteins localize differently in neurites of transfected PC12 pheochromocytoma cells. These findings indicate that alternative isoforms of SNAP-25 may play distinct roles in vesicular fusion events required for membrane addition during axonal outgrowth and for release of neuromodulatory peptides and neurotransmitters. PMID- 7878011 TI - Expression of a human alpha-1,3/4-fucosyltransferase in the pit cell lineage of FVB/N mouse stomach results in production of Leb-containing glycoconjugates: a potential transgenic mouse model for studying Helicobacter pylori infection. AB - Helicobacter pylori is a human pathogen associated with the development of gastric and duodenal ulcers and gastric adenocarcinoma. To test the hypothesis that the human Lewis(b) blood group antigen (Le(b)) functions as a receptor for the bacteria's adhesins and mediates its attachment to gastric pit and surface mucous cells, a human alpha-1,3/4-fucosyltransferase was expressed in these cell lineages in FVB/N transgenic mice. The fucosyltransferase directed production of the Leb epitope without any apparent effect on the proliferation and differentiation programs of this lineage. Moreover, clinical isolates of H. pylori bound to these cells in transgenic mice but not in their normal littermates. Binding was blocked by pretreatment of the bacteria with soluble Le(b). This mouse model could be useful for examining the molecular pathogenesis of diseases caused by H. pylori infection. Creating novel pathways for production of specific oligosaccharides in selected cell lineages of transgenic animals represents an approach for examining the role of complex carbohydrates in regulating cellular differentiation and host-microbe interactions. PMID- 7878012 TI - Tightly regulated, developmentally specific expression of the first open reading frame from LINE-1 during mouse embryogenesis. AB - LINE-1 (L1) has achieved its status as a middle repetitive DNA family in mammalian genomes by duplicative transposition. Although transposition may occur in any cell type, expression and transposition of a full-length functional element in the germ line are necessary for evolutionarily significant propagation of L1. An immunohistochemical analysis of adult mouse ovaries and mouse postimplantation embryos revealed expression of L1 open reading frame 1 in the germ line as well as in steroidogenic tissues. These results demonstrate that L1 expression is controlled by a tightly regulated temporal and spatial program of events during development and imply that multiple loci of L1 in the mouse genome are active for expression. PMID- 7878013 TI - Monocytes are required to prime peripheral blood T cells to undergo apoptosis. AB - Freshly isolated, human peripheral blood T (PBT) cells are largely resistant to the apoptotic effects of anti-CD3 monoclonal antibody, ionomycin, or phorbol 12 myristate 13-acetate (PMA). We demonstrate here, however, that PBT cells, including both CD4+ and CD8+ cell populations, can be readily induced to undergo apoptosis when cocultured with either autologous or allogeneic monocytes (Mo) in PMA-containing medium. Incubation of PBT cells with Mo at a ratio of 1:1 for 18 hr resulted in maximal levels (80%) of apoptotic cell death. The mechanism whereby Mo enable PBT cells to undergo apoptosis in PMA-containing medium appeared to depend on cell-cell contact or close proximity between Mo and PBT cells rather than solely via soluble mediators. It was demonstrated that Mo acquire the ability to prime PBT cells for apoptosis after treatment with PMA and that treated Mo maintain this ability even after fixation with formaldehyde. It was also found that once PBT cells became primed for apoptosis by incubation with PMA-pretreated Mo, the primed PBT cells were susceptible to apoptosis triggered not only by PMA but also by either ionomycin or by monoclonal antibody crosslinking of T-cell surface molecules such as CD4 and CD3. Interestingly, the degree of apoptosis of CD4+ T cells by crosslinking of CD4 molecules via a combination of gp120, anti-gp120, and goat anti-mouse IgG was significantly greater for T cells primed with PMA-treated Mo than for unprimed T cells. Together, these findings reveal an important role for accessory cells in priming resting PBT cells for apoptosis and suggest a possible Mo-dependent mechanism by which T cells may become primed for apoptosis in human immunodeficiency virus infected asymptomatic individuals. PMID- 7878014 TI - Protective immunity against tuberculosis induced by vaccination with major extracellular proteins of Mycobacterium tuberculosis. AB - Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, is the world's leading cause of death in humans from a single infectious agent. A safe and effective vaccine against this scourge is urgently needed. This study demonstrates that immunization with the 30-kDa major secretory protein, alone or in combination with other abundant extracellular proteins of M. tuberculosis, induces strong cell-mediated immune responses and substantial protective immunity against aerosol challenge with virulent M. tuberculosis bacilli in the highly susceptible guinea pig model of pulmonary tuberculosis. Protection is manifested by decreased clinical illness including decreased weight loss, reduced mortality, and decreased growth of M. tuberculosis in the lungs and spleens of immunized animals compared with sham-immunized controls. This study demonstrates that purified major extracellular proteins of M. tuberculosis are candidate components of a subunit vaccine against tuberculosis and provides compelling support for the concept that extracellular proteins of intracellular pathogens are key immunoprotective molecules. PMID- 7878015 TI - Transcription factor TFIIB and the vitamin D receptor cooperatively activate ligand-dependent transcription. AB - The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], regulates gene transcription through binding to the vitamin D receptor (VDR), a member of the nuclear hormone receptor superfamily. Sequence-specific transcription factors, including nuclear hormone receptors, are thought to interact with the basal transcription complex to regulate transcription. In glutathione S-transferase fusion-based protein-protein binding assays we found that VDR specifically binds to TFIIB, a component of the basal complex, and that the interaction requires select domains of each protein. To assess the functional significance of this interaction, transfection assays were performed with a 1,25(OH)2D3-responsive reporter construct. In P19 embryonal carcinoma cells cotransfection of VDR and TFIIB cooperatively activated reporter transcription, while each factor alone gave very low to no activation. This activation was dependent on 1,25(OH)2D3 and the dose of TFIIB and VDR transfected, demonstrating that a nuclear hormone receptor functionally interacts with TFIIB in vivo. In contrast, transfection of NIH 3T3 cells generated strong reporter activation by 1,25(OH)2D3 in the presence of VDR alone, and cotransfection of TFIIB led to specific dose-dependent repression of reporter activity. Taken together, these results indicate that TFIIB-nuclear hormone receptor interaction plays a critical role in ligand-dependent transcription, which is apparently modulated by a cell type-specific accessory factor. PMID- 7878016 TI - Segregation of cardiac and skeletal muscle-specific regulatory elements of the beta-myosin heavy chain gene. AB - The beta-myosin heavy chain (beta-MyHC) gene is expressed in cardiac and slow skeletal muscles. To examine the regulatory sequences that are required for the gene's expression in the two compartments in vivo, we analyzed the expression pattern of a transgene consisting of the beta-MyHC gene 5' upstream region linked to the chloramphenicol acetyltransferase reporter gene. By using 5600 bp of 5' upstream region, the transgene was expressed at high levels in the slow skeletal muscles. Decreased levels of thyroid hormone led to the up-regulation of the transgene in both cardiac and skeletal muscles, mimicking the behavior of the endogenous beta-MyHC gene. After deleting the distal 5000 bp, the level of reporter gene expression was strongly reduced. However, decreased levels of thyroid hormone led to an 80-fold skeletal muscle-specific increase in transgene expression, even upon the ablation of a conserved cis-regulatory element termed MCAT, which under normal (euthyroid) conditions abolishes muscle-specific expression. In contrast, cardiac-specific induction was not detected with the deletion construct. These observations indicate that the cardiac and skeletal muscle regulatory elements can be functionally segregated on the beta-MyHC gene promoter. PMID- 7878017 TI - Long-lived testosterone esters in the rat. AB - Over the past decade it has become increasingly clear that steroid hormones are enzymatically esterified with fatty acids. These steroidal esters are the natural analogs of synthetic esters that are used therapeutically. One such family of pharmacological steroids is the synthetic alkyl esters of testosterone, androgens with great hormonal potency. We have investigated whether testosterone esters exist naturally by using the rat as a model. Most tissues of male rats, including blood, have very little if any ester (quantified by immunoassay as a nonpolar saponifiable metabolite), but fat and testes have sizable quantities, approximately 3 ng of testosterone equivalents per g of tissue. Testosterone in fat averages 9 ng/g. The fat from female rats and long-term (> 2 weeks) castrated males has no detectable testosterone ester. The presence of testosterone esters was confirmed by GC/MS, which clearly showed the presence of testosterone in the hydrolyzed ester fraction of fat from intact males but not long-term castrates. Upon castration, testosterone levels in the fat completely disappear within 6 hr. To the contrary, it is not until 48 hr after castration that a measurable fall in the testosterone ester fraction was observed; even after 10 days a small amount of ester is still present in the fat. These experiments demonstrate the existence of a previously unknown androgen with a potentially important physiological impact; testosterone esters, natural analogs of potent therapeutic agents, occur in the fat where they can serve as a reservoir of preformed androgen to stimulate neighboring target tissues. PMID- 7878018 TI - Cleavage without anchor addition accompanies the processing of a nascent protein to its glycosylphosphatidylinositol-anchored form. AB - Rough microsomal membranes from most mammalian cells, in the presence of a translation system, process nascent proteins with appropriate COOH-terminal signal peptides to their mature glycosylphosphatidylinositol (GPI)-linked forms. The present study, using preprominiplacental alkaline phosphatase as substrate, shows that as much as 10% of the mature product is cleaved correctly but is not linked to GPI. Some of the factors that influence the relative proportions of GPI linked to free mini-placental alkaline phosphatase are the amounts of GPI in the cells and the amino acid substituent at the omega site of the nascent protein. A mechanism for explaining cleavage both with and without GPI addition is presented, which supports a transamidase type of enzyme as the catalyst. PMID- 7878019 TI - Identification of a neural-specific cDNA, NPDC-1, able to down-regulate cell proliferation and to suppress transformation. AB - Immortalized neural precursor cell lines carrying the polyoma large tumor (T) gene have been shown previously to retain a clear-cut contact inhibition of growth and to differentiate in vitro. In the present study, we have identified and isolated cDNA clones corresponding to RNA expressed preferentially when these cells reach confluence. One of them, NPDC-1, is expressed specifically in the nervous system. The transfection of dividing cells with a NPDC-1 expression vector results in the inhibition of cell proliferation. In addition, the stable introduction of NPDC-1 into transformed cells, even of nonneural origin, leads to the suppression of transformed characteristics. PMID- 7878020 TI - Biochemical evidence for the autophosphorylation and transphosphorylation of transforming growth factor beta receptor kinases. AB - Transforming growth factor beta (TGF-beta) signals through a receptor complex containing the type I (TGF-beta RI) and type II (TGF-beta RII) receptors. We describe here biochemical studies on early events in the TGF-beta signaling pathways. TGF-beta RII is highly phosphorylated when expressed alone in COS-1 cells; its autophosphorylation occurs via an intramolecular (cis) mechanism that is independent of ligand binding. TGF-beta RI is also highly phosphorylated when expressed alone in COS-1 cells. Both wild-type TGF-beta RI and a kinase-deficient mutant thereof are transphosphorylated by the coexpressed TGF-beta RII kinase in a ligand-independent fashion in these cells. We propose that the association of TGF-beta RI and TGF-beta RII, induced by ligand binding or over-expression, leads to transphosphorylation of the TGF-beta RI by the TGF-beta RII kinase. This represents a mechanism of activation of receptors distinct from that of tyrosine kinase receptors and may apply to other serine/threonine kinase receptors. PMID- 7878021 TI - Delineation of the minimal hepatitis B surface antigen-specific B- and T-cell epitope contained within an anti-idiotype-derived pentadecapeptide. AB - A pentadecapeptide (2F10 peptide) is capable of mimicking the group-specific "a" determinant of human hepatitis B surface antigen (HBsAg) at both the B- and the T cell level. This peptide represents a sequence on the heavy-chain hypervariable region of a monoclonal "internal image" anti-idiotype (anti-id 2F10) that has partial sequence homology to the "a" determinant epitope of HBsAg. To identify the exact location of the B- and T-cell epitopes, four truncated peptides (peptides 1-4) were synthesized. Using these truncated peptides we have identified the minimal sequence (octapeptide 3) that represents a functional B- and T-cell epitope capable of generating HBsAg-specific antibodies and T cells. This to our knowledge represents the first example of a short peptide sequence functioning as both a B- and a T-cell epitope. We have also identified another T cell epitope (2F10 peptide 4), but this peptide fails to elicit HBsAg-specific B cells and T cells. Thus, the 2F10 pentadecapeptide is composed of two nonoverlapping, functional T-cell epitopes only one of which is HBsAg specific. Since peptide 3 represents the complementarity-determining region and peptide 4 represents the framework region of the anti-id 2F10, we conclude that an 8-aa sequence from the complementarity-determining region of anti-id 2F10 is sufficient for the molecular mimicry of HBsAg. Finally, our experiments suggest that sequences flanking the minimal immunodominant epitope exert a considerable influence on the nature of antigenic processing that occurs and the resultant T cell reactivity elicited. PMID- 7878022 TI - Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms. AB - Effects of the stable somatostatin analogue RC-160 on cell proliferation, tyrosine phosphatase activity, and intracellular calcium concentration were investigated in CHO cells expressing the five somatostatin receptor subtypes SSTR1 to -5. Binding experiments were performed on crude membranes by using [125I labeled Tyr11] somatostatin-14; RC-160 exhibited moderate-to-high affinities for SSTR2, -3, and -5 (IC50, 0.17, 0.1 and 21 nM, respectively) and low affinity for SSTR1 and -4 (IC50, 200 and 620 nM, respectively). Cell proliferation was induced in CHO cells by 10% (vol/vol) fetal calf serum, 1 microM insulin, or 0.1 microM cholecystokinin (CCK)-8; RC-160 inhibited serum-induced proliferation of CHO cells expressing SSTR2 and SSTR5 (EC50, 53 and 150 pM, respectively) but had no effect on growth of cells expressing SSTR1, -3, or -4. In SSTR2-expressing cells, orthovanadate suppressed the growth inhibitory effect of RC-160. This analogue inhibited insulin-induced proliferation and rapidly stimulated the activity of a tyrosine phosphatase in only this cellular clone. This latter effect was observed at doses of RC-160 (EC50, 4.6 pM) similar to those required to inhibit growth (EC50, 53 pM) and binding to the receptor (IC50, 170 pM), implicating tyrosine phosphatase as a transducer of the growth inhibition signal in SSTR2-expressing cells. In SSTR5-expressing cells, the phosphatase pathway was not involved in the inhibitory effect of RC-160 on cell growth, since this action was not influenced by tyrosine and serine/threonine phosphatase inhibitors. In addition, in SSTR5 expressing cells, RC-160 inhibited CCK-stimulated intracellular calcium mobilization at doses (EC50, 0.35 nM) similar to those necessary to inhibit somatostatin-14 binding (IC50, 21 nM) and CCK-induced cell proliferation (EC50, 1.1 nM). This suggests that the inositol phospholipid/calcium pathway could be involved in the antiproliferative effect of RC-160 mediated by SSTR5 in these cells. RC-160 had no effect on the basal or carbachol-stimulated calcium concentration in cells expressing SSTR1 to -4. Thus, we conclude that SSTR2 and SSTR5 bind RC-160 with high affinity and mediate the RC-160-induced inhibition of cell growth by distinct mechanisms. PMID- 7878024 TI - A mechanical strain-induced 1-aminocyclopropane-1-carboxylic acid synthase gene. AB - Ethylene production is observed in all higher plants, where it is involved in numerous aspects of growth, development, and senescence. 1-Aminocyclopropane-1 carboxylic acid synthase (ACC synthase; S-adenosyl-L-methionine methylthioadenosine-lyase, EC 4.4.1.14) is the key regulatory enzyme in the ethylene biosynthetic pathway. We are reporting an ACC synthase gene in Vigna radiata (mung bean) that is inducible by mechanical strain. The ACC synthase cDNA AIM-1 was induced by mechanical strain within 10 min, reaching a maximum at 30 min, showing a dramatic reduction after 60 min, and showing no detectable message by 3 hr. The kinetics of induction for AIM-1 was similar to a mechanical strain induced calmodulin (MBCaM-1) in V. radiata, whereas the kinetics of its decline from maximum was different. When plants were subjected to calcium-deficient conditions, supplemental calcium, calcium chelators, calcium storage releasers, calcium ionophore, or calmodulin antagonists, there was no effect on AIM-1, indicating that the mechanical strain-induced AIM-1 expression is a calcium independent process. Induction of MBCaM-1 in all cases behaved in the same way as AIM-1, suggesting that they share similar mechanically activated cis- and/or trans-acting elements in their promoter. PMID- 7878023 TI - Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia. AB - Studies by various investigators have indicated that elevated levels of plasma homocyst(e)ine are strongly associated with the occurrence of occlusive vascular diseases. With the eventual aim of determining whether or not elevated plasma homocyst(e)ine concentrations are directly causative of cardiovascular diseases, we have generated mice that are moderately and severely homocyst(e)inemic. Homologous recombination in mouse embryonic stem cells was used to inactivate the cystathionine beta-synthase [L-serine hydrolyase (adding homocysteine), EC 4.2.1.22] gene. Homozygous mutants completely lacking cystathionine beta-synthase were born at the expected frequency from matings of heterozygotes, but they suffered from severe growth retardation and a majority of them died within 5 weeks after birth. Histological examination showed that the hepatocytes of homozygotes were enlarged, multinucleated, and filled with microvesicular lipid droplets. Plasma homocyst(e)ine levels of the homozygotes were approximately 40 times normal. These mice, therefore, represent a model for severe homocyst(e)inemia resulting from the complete lack of cystathionine beta synthase. Heterozygous mutants have approximately 50% reduction in cystathionine beta-synthase mRNA and enzyme activity in the liver and have twice normal plasma homocyst(e)ine levels. Thus, the heterozygous mutants are promising for studying the in vivo role of elevated levels of homocyst(e)ine in the etiology of cardiovascular diseases. PMID- 7878025 TI - The fungal H(+)-ATPase from Neurospora crassa reconstituted with fusicoccin receptors senses fusicoccin signal. AB - Fusicoccin affects several physiological processes regulated by the plasma membrane H(+)-ATPase in higher plants while other organisms having P-type H(+) ATPases (e.g., fungi) are fusicoccin-insensitive. We have previously shown that fusicoccin binding to its receptor is necessary for H(+)-ATPase stimulation and have achieved the functional reconstitution into liposomes of fusicoccin receptors and the H(+)-ATPase from maize. In this paper we show that fusicoccin sensitivity can be conferred on the H(+)-ATPase from Neurospora crassa, a fungus insensitive to fusicoccin. In fact, H+ pumping by purified H(+)-ATPase from Neurospora crassa reconstituted into liposomes containing crude or partially purified fusicoccin receptors from maize was markedly enhanced by fusicoccin. The stimulation of H+ pumping by fusicoccin is dependent upon pH, fusicoccin, and protein concentration, as was reported for the system reconstituted with both proteins from maize. PMID- 7878027 TI - Display of peptides and proteins on the surface of bacteriophage lambda. AB - The display of peptides or proteins on the surface of viruses is an important technology for studying peptides or proteins and their interaction with other molecules. Here we describe a display vehicle based on bacteriophage lambda that incorporates a number of features distinct from other currently used display systems. Fusions of peptides or protein domains have been made to the amino terminus of the 11-kDa D protein of the lambda capsid. These fusions assemble onto the viral capsid and appear to be accessible to ligand interactions, based on the ability of a monoclonal antibody to recognize an epitope fused to the D protein on phage heads. To produce large D fusion display libraries and yet avoid the cumbersome task of cloning many fragments into lambda DNA, we have used the Cre-loxP site-specific recombination system in vivo to incorporate plasmids encoding the D fusions into the phage genome. Finally, we show that D fusion proteins can be added in vitro to phage lacking D protein and be assembled onto the viral capsid. PMID- 7878026 TI - Possible proton relay pathways in cytochrome c oxidase. AB - As the final electron acceptor in the respiratory chain of eukaryotic and many prokaryotic organisms, cytochrome c oxidase (EC 1.9.3.1) catalyzes the reduction of oxygen to water and generates a proton gradient. To test for proton pathways through the oxidase, site-directed mutagenesis was applied to subunit I of the Rhodobacter sphaeroides enzyme. Mutants were characterized in three highly conserved regions of the peptide, comprising possible proton loading, unloading, and transfer sites: an interior loop between helices II and III (Asp132Asn/Ala), an exterior loop between helices IX and X (His411Ala, Asp412Asn, Thr413Asn, Tyr414Phe), and the predicted transmembrane helix VIII (Thr352Ala, Pro358Ala, Thr359Ala, Lys362Met). Most of the mutants had lower activity than wild type, but only mutants at residue 132 lost proton pumping while retaining electron transfer activity. Although electron transfer was substantially inhibited, no major structural alteration appears to have occurred in D132 mutants, since resonance Raman and visible absorbance spectra were normal. However, lower CO binding (70 85% of wild type) suggests some minor change to the binuclear center. In addition, the activity of the reconstituted Asp132 mutants was inhibited rather than stimulated by ionophores or uncoupler. The inhibition was not observed with the purified enzyme and a direct pH effect was ruled out, suggesting an altered response to the electrical or pH gradient. The results support an important role for the conserved II-III loop in the proton pumping process and are consistent with the possibility of involvement of residues in helix VIII and the IX-X loop. PMID- 7878028 TI - Tumor necrosis factor alpha rapidly activates the mitogen-activated protein kinase (MAPK) cascade in a MAPK kinase kinase-dependent, c-Raf-1-independent fashion in mouse macrophages. AB - Tumor necrosis factor alpha (TNF alpha) is bound by two cell surface receptors, CD120a (p55) and CD120b (p75), that belong to the TNF/nerve growth factor receptor family and whose signaling is initiated by receptor multimerization in the plane of the plasma membrane. The initial signaling events activated by receptor crosslinking are unknown, although activation of the mitogen-activated protein kinase (MAPK) cascade occurs shortly after ligand binding to CD120a. In this study, we investigated the upstream kinases that mediate the activation of the 42-kDa MAPK p42mapk/erk2 following crosslinking of CD120a in mouse macrophages. Exposure of mouse macrophages to TNF alpha stimulated a time dependent increase in the activity of MAPK/ERK kinase (MEK) that temporally preceded peak activation of p42mapk/erk2. MEKs, dual-specificity threonine/tyrosine kinases, act as a convergence point for several signaling pathways including Ras/Raf, MEK kinase (MEKK), and Mos. Incubation of macrophages with TNF alpha was found to transiently stimulate a MEKK that peaked in activity within 30 sec of exposure and progressively declined toward basal levels by 5 min. By contrast, under these conditions, activation of either c-Raf-1 or Raf-B was not detected. These data suggest that the activation of the MAPK cascade in response to TNF alpha is mediated by the sequential activation of a MEKK and a MEK in a c-Raf-1- and Raf-B-independent fashion. PMID- 7878029 TI - Recombinant rat CBF-C, the third subunit of CBF/NFY, allows formation of a protein-DNA complex with CBF-A and CBF-B and with yeast HAP2 and HAP3. AB - The CCAAT binding factor CBF is a heteromeric transcription factor, which binds to functional CCAAT motifs in many eukaryotic promoters. cDNAs for the A and B subunits of CBF (CBF-A and CBF-B) and for their yeast homologues HAP3 and HAP2 have been previously isolated, but the purified recombinant CBF-A and CBF-B together are unable to bind to CCAAT motifs in DNA. Here we report the isolation of a cDNA coding for rat CBF-C, demonstrate that recombinant CBF-C is required together with CBF-A and CBF-B to form a CBF-DNA complex, and show that CBF-C is present in this protein-DNA complex together with the other two subunits. We further show that CBF-C allows formation of a complex between the purified recombinant yeast HAP2 and HAP3 polypeptides and a CCAAT-containing DNA and is present in this complex, implying the existence of a CBF-C homologue in yeast. We show that CBF-A and CBF-C interact with each other to form a CBF-A-CBF-C complex and that CBF-B does not interact with CBF-A or CBF-C individually but that it associates with the CBF-A-CBF-C complex. Our results indicate that CBF is a unique evolutionarily conserved DNA binding protein. PMID- 7878030 TI - The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1). AB - p150Glued was first identified as a polypeptide that copurifies with cytoplasmic dynein, the minus-end-directed microtubule-based motor protein, and has more recently been shown to be present as a member of the oligomeric dynactin complex, which includes the actin-related protein centractin (Arp-1). Dynactin is thought to mediate dynein-driven vesicle motility, as well as nuclear transport, in lower eukaryotes. The mechanism by which dynactin may function in these cellular processes is unknown. To examine the role of the dynactin complex in vivo, we overexpressed the rat cDNA encoding p150Glued in Rat-2 fibroblasts. Overexpression of full-length, as well as C-terminal deletion, constructs resulted in the decoration of microtubules with the p150Glued polypeptides. This cellular evidence for microtubule association was corroborated by in vitro microtubule-binding assays. Amino acids 39-150 of p150Glued were determined to be sufficient for microtubule association. We also tested for a direct interaction between p150Glued and centractin. In vitro translated centractin was specifically retained by a p150Glued affinity column, and this interaction was blocked by a synthetic peptide which corresponds to a highly conserved motif from the C terminus of p150Glued. These results demonstrate that p150Glued, a protein implicated in cytoplasmic dynein-based microtubule motility, is capable of direct binding to both microtubules and centractin. PMID- 7878032 TI - Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants. AB - A nontoxic mutant (LTK7) of the Escherichia coli heat-labile enterotoxin (LT) lacking ADP-ribosylating activity but retaining holotoxin formation was constructed. By using site-directed mutagenesis, the arginine at position 7 of the A subunit was replaced with lysine. This molecule, which was nontoxic in several assays, was able to bind to eukaryotic cells and acted as a mucosal adjuvant for co-administered proteins; BALB/c mice immunized intranasally with LTK7 and ovalbumin developed high levels of serum and local antibodies to ovalbumin and toxin. In addition, mice immunized intranasally with fragment C of tetanus toxin and LTK7 were protected against lethal challenge with tetanus toxin. Thus nontoxic mutants of heat-labile toxin can act as effective intranasal mucosal adjuvants. PMID- 7878031 TI - Two short autoepitopes on the nuclear dot antigen are similar to epitopes encoded by the Epstein-Barr virus. AB - To understand the relationship between antibodies present in patients with anti nuclear dot (ND) autoimmune disease and the proteins they recognize, epitopes that react with the autoantibodies were mapped. A panel of fusion proteins containing different portions of the ND protein were overproduced in Escherichia coli. Immunoblot analysis with anti-ND antibodies revealed that most (10 of 12) sera recognize two major autoepitopes that are each a maximum of 8 amino acids long. The other two sera recognize one of the two epitopes. In addition to the short linear autoepitopes, a conformational epitope appears to be present on the ND antigen. Each of the two linear epitope sequences shares sequence similarities with those of several viral proteins found in the databases. Furthermore, two fusion proteins containing short Epstein-Barr virus (EBV) protein sequences that are similar to the ND epitopes were recognized by the human autoimmune sera, indicating that the autoepitopes are present in EBV protein sequences. Our results are consistent with the hypothesis that ND autoimmune disease might be associated with EBV infections. PMID- 7878033 TI - Altered phenotype and function of natural killer cells expressing the major histocompatibility complex receptor Ly-49 in mice transgenic for its ligand. AB - The Ly-49 molecule has been shown to interact with major histocompatibility complex (MHC) class I molecules, and the lytic function of Ly-49+ natural killer (NK) cells from C57BL/6 (H-2b) mice is inhibited by the recognition of H-2Dd on tumor target cells. Introduction of a Ly-49 ligand, H-2Dd, into C57BL/6 mice did not alter the percentage of Ly-49+ NK cells (13-18%), but it led to three functional effects on this subset. (i) The Ly-49 expression in the positive population was reduced by 30-50% compared to C57BL/6 control mice. (ii) While this Ly-49+ subset (Ly-49lo) in the transgenic mice failed to kill BALB/c concanavalin A (Con A) blasts, which have high H-2Dd expression, it was capable of killing SP2/0 tumor cells, which have low H-2Dd expression. Ly-49+ NK cells (Ly-49hi) from nontransgenic mice failed to kill both of these H-2Dd-expressing target cells. (iii) In the transgenic mice, the Ly-49+ subset acquired the ability to kill C57BL/6 Con A blasts, in contrast to the Ly-49+ NK cells of C57BL/6 mice. We propose a "receptor-calibration" hypothesis, where low receptor density on the effector cells imposed by selection or adaptation to the environment allows higher sensitivity for detection of reduced self-MHC ligands on potential target cells. PMID- 7878034 TI - Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis. AB - In many cervical cancers, human papillomavirus type 16 (HPV-16) DNA genomes are found to be integrated into the host chromosome. In this study, we demonstrate that integration of HPV-16 DNA leads to increased steady-state levels of mRNAs encoding the viral oncogenes E6 and E7. This increase is shown to result, at least in part, from an increased stability of E6 and E7 mRNAs that arise specifically from those integrated viral genomes disrupted in the 3' untranslated region of the viral early region. Further, we demonstrate that the A+U-rich element within this viral early 3' untranslated region confers instability on a heterologous mRNA. We conclude that integration of HPV-16 DNA, as occurs in cervical cancers, can result in the increased expression of the viral E6 and E7 oncogenes through altered mRNA stability. PMID- 7878035 TI - Functional identification of the promoter for the gene encoding the alpha subunit of calcium/calmodulin-dependent protein kinase II. AB - To examine the expression of the alpha subunit of calcium/calmodulin-dependent protein kinase II, various 5' flanking genomic sequences were inserted into a chloramphenicol acetyltransferase (CAT) reporter plasmid and CAT enzyme activities were analyzed in transfected NB2a neuroblastoma cells and mRNA transcription was analyzed by nuclease protection assays. A core promoter was identified which contained an essential TATA element located 162 nt 5' to the transcription start site. Sequences 3' to the transcription start site, as well as 5' to the TATA element, increased levels of CAT activity in transfected cells. The alpha-subunit gene promoter displayed higher CAT activities, relative to a simian virus 40 promoter, in transfected neuronal cell lines than in nonneuronal cell lines. Results also suggested that sequence surrounding the natural alpha gene transcription initiation site may be important for targeting transcription initiation 162 nt downstream of its TATA element. PMID- 7878036 TI - A genetic locus of enterocyte effacement conserved among diverse enterobacterial pathogens. AB - Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli O157:H7 are intestinal pathogens that profoundly damage the microvilli and subapical cytoskeleton of epithelial cells. Here we report finding in EPEC a 35-kbp locus containing several regions implicated in formation of these lesions. DNA probes throughout this locus hybridize to E. coli O157:H7 and other pathogens of three genera that cause similar lesions but do not hybridize to avirulent members of the same species. The EPEC locus and a different virulence locus of uropathogenic E. coli insert into the E. coli chromosome at the identical site and share highly similar sequences near the point of insertion. PMID- 7878037 TI - Dopamine receptors in the substantia nigra are involved in the regulation of muscle tone. AB - The aim of the present study was to localize the dopamine receptors involved in the regulation of muscle tone. A strategy was used whereby the effects on muscle tone of injecting the irreversible dopamine receptor antagonist N-ethoxycarbonyl 2-ethoxy-1,2-dihydroquinoline (EEDQ) in discrete brain regions were assessed. Increases in muscle tone were measured as changes in electromyographic activity of the gastrocnemius and tibialis muscles of conscious, unrestrained rats. No increases in muscle tone were found after injections of EEDQ into the anterior and posterior striatum, which produced marked reductions in dopamine receptor concentration. The effects of muscle tone of injecting EEDQ into the substantia nigra pars reticulata were also assessed. Large increases in muscle tone were observed associated with inactivation of either D1 or D2 dopamine receptors in the substantia nigra. The increased muscle tone was not reduced by subcutaneous administration of apomorphine, despite the presence of a normal population of striatal dopamine receptors. These findings provide evidence that dopamine receptors in the substantia nigra play an important role in the regulation of muscle tone. Further, they challenge the hypothesis that the muscle rigidity of Parkinson disease results primarily from loss of striatal dopamine receptor stimulation. PMID- 7878038 TI - Retroviral-mediated gene transfer corrects very-long-chain fatty acid metabolism in adrenoleukodystrophy fibroblasts. AB - Adrenoleukodystrophy (ALD), a lethal demyelinating disease of the brain, is caused by mutations of a gene encoding an ATP-binding transporter, called ALDP, localized in the peroxisomal membrane. It is associated with a defective oxidation of very-long-chain fatty acids, leading to their accumulation in many tissues. This study reports that the retroviral-mediated transfer of the ALD cDNA restored very-long-chain fatty acid oxidation in ALD fibroblasts in vitro following abundant expression and appropriate targeting of the vector-encoded ALDP in peroxisomes. The same method may be used in hematopoietic cells as a further step of a gene therapy approach of ALD. PMID- 7878039 TI - Cytoplasmic inhibition of carotenoid biosynthesis with virus-derived RNA. AB - The carotenoid biosynthetic pathway in higher plants was manipulated by using an RNA viral vector. A cDNA encoding phytoene synthase and a partial cDNA encoding phytoene desaturase (PDS) were placed under the transcriptional control of a tobamovirus subgenomic promoter. One to two weeks after inoculation, systemically infected Nicotiana benthamiana plants were analyzed for phytoene. Leaves from transfected plants expressing phytoene synthase developed a bright orange phenotype and accumulated high levels of phytoene. Cytoplasmic inhibition of plant gene expression by viral RNA was demonstrated with an antisense RNA transcript to a partial PDS cDNA derived from tomato. The leaves of the plants transfected with the antisense PDS sequence developed a white phenotype and also accumulated high levels of phytoene. A partial cDNA to the corresponding N. benthamiana PDS gene was isolated and found to share significant homology with the tomato antisense PDS transcript. This work demonstrates that an episomal RNA viral vector can be used to deliberately manipulate a major, eukaryotic biosynthetic pathway. In addition, our results indicate that an antisense transcript generated in the cytoplasm of a plant cell can turn off endogenous gene expression. PMID- 7878040 TI - Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes. AB - Comparative vertebrate genome sequencing offers a powerful method for detecting conserved regulatory sequences. We propose that the compact genome of the teleost Fugu rubripes is well suited for this purpose. The evolutionary distance of teleosts from other vertebrates offers the maximum stringency for such evolutionary comparisons. To illustrate the comparative genome approach for F. rubripes, we use sequence comparisons between mouse and Fugu Hoxb-4 noncoding regions to identify conserved sequence blocks. We have used two approaches to test the function of these conserved blocks. In the first, homologous sequences were deleted from a mouse enhancer, resulting in a tissue-specific loss of activity when assayed in transgenic mice. In the second approach, Fugu DNA sequences showing homology to mouse sequences were tested for enhancer activity in transgenic mice. This strategy identified a neural element that mediates a subset of Hoxb-4 expression that is conserved between mammals and teleosts. The comparison of noncoding vertebrate sequences with those of Fugu, coupled to a transgenic bioassay, represents a general approach suitable for many genome projects. PMID- 7878041 TI - Scalp electrical potentials reflect regional cerebral blood flow responses during processing of written words. AB - Functional brain imaging studies with positron emission tomography (PET) have identified blood flow changes in widely separated areas of the brain during the performance of word-related tasks. In the present study, we have utilized event related electrical potentials (ERPs) to investigate the temporal relationships among cortical areas previously identified by PET to be differentially activated when performing a task involving generating the uses of visually presented nouns versus reading aloud. ERPs showed strong task-related differences over left and middle inferior frontal and left parietotemporal regions. Frontal and left parietotemporal channels revealed these differences around 200 and 700 msec, respectively, after word presentation. These results provide the time course for parts of the anatomical circuit involved in generating the meaning of a word. Our results also demonstrate how combining the spatial localization of PET with the temporal resolution of ERPs greatly enhances the capacity to understand the mechanisms involved in human cognition. PMID- 7878042 TI - Mechanistically different catalytic antibodies obtained from immunization with a single transition-state analog. AB - The variable-region peptide sequence and steady-state kinetic behavior are compared for a family of catalytic antibodies that arose from the same immune response to a transition-state analog. The crystal structure of the most catalytically active member of the family (17E8) has been solved to 2.5 A resolution and shows that the antibody active site contains a SerH99-HisH35 (H = heavy chain) catalytic dyad analogous to the Ser-His-Asp catalytic triad of serine proteases. The variable-region peptide sequence of the next most active antibody (29G11) differs from that of 17E8 by nine heavy-chain point mutations, and results from computer modeling suggest that the three-dimensional structure of 29G11 is similar to that of 17E8. In addition, 29G11 is an efficient catalytic antibody; it possesses 26% of the hydrolytic activity of 17E8. There is one active-site mutation in 29G11 compared to 17E8; position 99 of the heavy chain of 29G11 contains a glycine residue in place of the nucleophilic serine at this position in 17E8. Consistent with this mutation, results from pH-rate studies and hydroxylamine partitioning experiments indicate that in contrast to the catalytic mechanism of 17E8, the mechanism of 29G11-catalyzed esterolysis does not feature nucleophilic catalysis. PMID- 7878044 TI - Mutant farnesyltransferase beta subunit of Saccharomyces cerevisiae that can substitute for geranylgeranyltransferase type I beta subunit. AB - The protein farnesyltransferase (PFT) beta-subunit gene of Saccharomyces cerevisiae, DPR1, was randomly mutagenized by PCR to construct a mutant DPR1 gene library on a high-copy plasmid. The library was screened for suppression of the temperature sensitivity conferred by a mutation in the protein geranylgeranyltransferase type I (PGGT-I) beta-subunit gene, CAL1. A mutant DPR1 gene was identified whose product contained a single amino acid change of Ser-159 to Asn. This mutant gene also suppressed a cal1 disruption even on a low-copy plasmid, suggesting that the product (designated S159N) can substitute for PGGT-I beta subunit in vivo. Its ability to act as a PFT is not drastically reduced, since the mutant gene still complemented a dpr1 disruption. Results of in vitro assays demonstrate that the mutant enzyme has increased activity to farnesylate, a substrate for PGGT-I. On the other hand, the ability to farnesylate its own substrate is reduced. The increased ability to utilize the PGGT-I substrate is due to its increased affinity for the protein substrate. In addition, the mutant enzyme shows a severalfold increase in the sensitivity to a peptidomimetic inhibitor that acts as a competitor of the protein substrate. These results point to the importance of the beta subunit of PFT for the binding of a protein substrate and demonstrate that Ser-159 of DPR1 product is critical for its substrate specificity. PMID- 7878045 TI - The murine N-ras gene is not essential for growth and development. AB - The mammalian ras gene family encodes key cell-signaling, cell growth-related proteins that have been highly conserved in species from yeast to man. Specific point mutations in the ras genes are associated with various mammalian tumors. To understand the developmental role of the N-ras protooncogene in the mouse, we have disrupted its gene function by homologous recombination in embryonic stem cells. Mice derived from these cells that are homozygous for the N-ras mutation do not produce any detectable N-Ras protein and are morphologically and histologically indistinguishable from their heterozygous and wild-type siblings. Since N-ras is expressed at high levels in hematopoietic cells, we examined different populations of cells in peripheral blood and found no differences between mutant and normal animals. Our results show that N-ras gene function is dispensable for normal mouse development, growth, and fertility. PMID- 7878043 TI - Structural characterization of a minimal functional transactivation domain from the human glucocorticoid receptor. AB - A 58-amino acid polypeptide containing the functional core region, the tau 1 core, of the major transactivation domain of the human glucocorticoid receptor has been expressed in Escherichia coli and purified to homogeneity. The polypeptide retains 60-70% of the activity of the intact domain when assayed in vivo or in vitro. This report describes a structural characterization of the tau 1 core peptide fragment. Circular dichroism spectroscopy shows that the tau 1 core and a larger fragment encompassing the intact tau 1 domain are largely unstructured in water solution under a variety of pH conditions. The tau 1 core, however, acquires a significant alpha-helical structure when analyzed in the presence of trifluoroethanol, an agent that favors secondary structure formation in regions that have propensity for alpha-helical conformation. Two- and three dimensional NMR spectroscopy of 15N-labeled tau 1 core, in the presence of trifluoroethanol, has allowed sequential assignment of 1H and 15N resonances and identification of three protein segments with alpha-helical character. Potentially helix-breaking proline substitutions, in proposed alpha-helical regions, lead to reduced activity, suggesting that alpha-helices are important for transactivation in vivo. PMID- 7878046 TI - Soluble type II interleukin 1 (IL-1) receptor binds and blocks processing of IL-1 beta precursor and loses affinity for IL-1 receptor antagonist. AB - Two IL-1 receptors have been identified, termed type I and type II. The extracellular domain of the type II IL-1 receptor is released from certain cells and can function as a specific inhibitor of IL-1 beta activity. We assessed the ligand-binding properties of the type II membrane-bound and soluble IL-1 receptor (sIL-1R) from the human B cell line Raji by competition. Upon release, the affinity of sIL-1R for IL-1 alpha and IL-1 beta remained constant, and both soluble and cell surface IL-1 receptors bound to the same regions on the IL-1 beta molecule as defined by binding of a series of IL-1 beta mutant molecules. However, the affinity of sIL-1R for the IL-1 receptor antagonist (IL-1ra) decreased by a factor of 2000 when compared with the cell surface receptor. Type II sIL-1R and IL-1ra had an additive effect in inhibiting the binding of IL-1 beta to cell surface IL-1 receptors. In contrast, the combination of recombinant type 1 sIL-1R with IL-1ra abrogated the inhibition seen with each of the individual agents alone. The type II cell surface IL-1 receptor failed to bind the biologically inactive IL-1 beta precursor molecule, but binding to the IL-1 beta precursor was observed on cellular release of the receptor; this was confirmed with 35S-labeled IL-1 beta. Binding of IL-1 beta precursor by sIL-1R inhibited the precursor's ability to be processed to the mature, biologically active 17-kDa species. These observations suggest that the type II sIL-1R inhibits IL-1 beta at two steps, by preventing processing of propeptide and by blocking the interaction of mature IL-1 beta with type I IL-1 receptor. In addition, type II sIL-1R does not interfere with inhibition mediated by IL-1ra. PMID- 7878048 TI - Transient protein kinase C activation primes long-term depression and suppresses long-term potentiation of synaptic transmission in hippocampus. AB - Activity-dependent long-lasting plasticity in hippocampus and neocortex includes long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength. Recent studies have confirmed theoretical predictions that the sensitivity of LTP and LTD-inducing mechanisms is dynamically regulated by previous synaptic history. In particular, prior induction of either repeated short-term potentiations or LTP lowers the threshold for induction of LTD and raises the threshold for LTP. In the current study, transient activation of protein kinase C with phorbol 12,13-diacetate was able to substitute for synaptic activity in priming synapses to exhibit enhanced homosynaptic LTD and to suppress the induction of LTP at Schaffer collateral synapses in area CA1 of hippocampal slices. This priming lasted 30 min, but not 3 hr, following phorbol 12,13 diacetate bath application. These data suggest that a protein kinase C-sensitive phosphorylation site may be an activity-sensitive target mediating the rapid expression of LTP and LTD. PMID- 7878049 TI - Characterization of two nuclear mammalian homologous DNA-pairing activities that do not require associated exonuclease activity. AB - We have developed an assay to study homologous DNA-pairing activities in mammalian nuclear extracts. This assay is derived from the POM blot assay, described earlier, which was specific for RecA activity in bacterial crude extracts. In the present work, proteins from mammalian nuclear extracts were resolved by electrophoresis on SDS/polyacrylamide gels and then electrotransferred onto a nitrocellulose membrane coated with circular single stranded DNA (ssDNA). The blot obtained was incubated with a labeled homologous double-stranded DNA (dsDNA). Homologous pairing between the ssDNA and the labeled dsDNA was detected by autoradiography as a radioactive spot on the membrane. In nuclear extracts from mammalian cells, we found two major polypeptides of 100 and 75 kDa, able to promote the formation of stable plectonemic joints. Joint molecule formation required at least one homologous end on the dsDNA, but either end of the dsDNA could be recruited to initiate the reaction. For each polypeptide, the reaction required divalent cations such as Mg2+, Ca2+, or Mn2+. Although ATP was not necessary, ADP was inhibitory in each case. Unlike most of the known eukaryotic DNA-pairing proteins, both activities identified here were able to promote the formation of joint molecules without requiring an associated exonuclease activity. In addition, these two proteins were detected in cell lines from different tissues and from different mammalian species (human, mouse, and hamster). PMID- 7878047 TI - A paradoxical regulation of the dopamine D3 receptor expression suggests the involvement of an anterograde factor from dopamine neurons. AB - The effects of interruption of dopaminergic transmission or sustained blockade of dopamine receptors by neuroleptics on the dopamine D3 receptor in the shell of the nucleus accumbens were investigated in rats. In this brain area the D3 receptor is abundant and may mediate antipsychotic drug effects. The D3 receptor density and mRNA abundance were evaluated with 7-[3H]hydroxy-N,N-di-n-propyl-2 aminotetralin and by quantitative PCR or image analysis of in situ hybridization signals, respectively. Unilateral dopamine neuron degeneration by 6 hydroxydopamine or sections triggered, after a few days, a marked decrease (up to 50%) in D3 receptor binding and mRNA in the nucleus accumbens. In contrast, a 2 week treatment with the neuroleptic haloperidol (20 mg/kg) had no effect on D3 receptor density and mRNA but enhanced D2 receptor density and mRNA level by > 50%. In addition, tolerance to the haloperidol-induced change of neurotensin mRNA mediated by the D2 receptor developed, but there was no tolerance to the opposite change mediated by the D3 receptor. Reserpine, a monoamine-depleting drug with antipsychotic activity, did not modify D3 receptor mRNA. These observations reinforce the idea that the D3 receptor may be an important target for neuroleptics whose antipsychotic actions, but not extrapyramidal motor actions, do not display tolerance. The D3 receptor mRNA level was also decreased by a unilateral injection in dopamine cell body areas of colchicine, a drug blocking the anterograde axonal transport, or by baclofen, a type A gamma-aminobutyric acid receptor agonist reducing dopamine neuron activity, but not by sustained blockade of D1-like and D2-like, neurotensin, or cholecystokinin receptors. We therefore propose that an anterograde factor present in mesolimbic dopaminergic neurons, but distinct from dopamine and known peptide cotransmitters, plays a positive role on transcription of the D3 receptor gene. PMID- 7878050 TI - Differential expression of mRNAs for protein kinase inhibitor isoforms in mouse brain. AB - Many neurotransmitters are known to regulate neuronal cell function by means of activation of cAMP-dependent protein kinase (PKA) and phosphorylation of neuronal substrate proteins, including transcription factors and ion channels. Here, we have characterized the gene expression of two isoforms of a protein kinase inhibitor (PKI) specific for PKA in mouse brain by RNase protection and in situ hybridization histochemistry. The studies demonstrate that the PKI alpha isoform is abundant in many regions of the adult mouse brain but particularly in cerebellum, hypothalamus, hippocampus, and cortex. In contrast, PKI beta is present at much lower levels in most brain regions but is found in significant amounts in the cerebellum, as well as in distinct nuclei within the pons, medulla, and hypothalamus. These results are consistent with a regulatory role of endogenous PKI in PKA-mediated signal transduction in brain and suggest differential functions for the two isoforms of PKI within the central nervous system. PMID- 7878051 TI - Translocation of the Escherichia coli transcription complex observed in the registers 11 to 20: "jumping" of RNA polymerase and asymmetric expansion and contraction of the "transcription bubble". AB - Translocation of DNA-dependent RNA polymerase along the DNA template during RNA synthesis encompasses continuous as well as discontinuous steps. This is demonstrated by chemical probing of transcription complexes stalled in consecutive registers of RNA synthesis at base positions +11, +12, +14, +16, +18, and +20. The "transcription bubble" translocates by continuous opening of the downstream edge in tandem with the growing RNA chain and discontinuous closing at the upstream edge after at least nine steps of RNA synthesis. The position of the enzyme remains unchanged during extension of the transcription bubble and "jumps" 10 bp downstream simultaneously with collapse of the transcription bubble. PMID- 7878052 TI - Targeted gene transfer into hepatoma cells with lipopolyamine-condensed DNA particles presenting galactose ligands: a stage toward artificial viruses. AB - Optimal in vitro gene delivery with cationic lipids requires an excess of cationic charges with respect to DNA phosphates. In these conditions, in vivo delivery will be hampered by interference from cationic lipid-binding macromolecules either circulating or in the extracellular matrix. To overcome this problem, we are developing a modular transfection system based on lipid coated DNA particles reminiscent of enveloped viruses. The particle core consists of the lipopolyamine-condensed nucleic acid in an electrically neutral ratio to which other synthetic lipids with key viral properties are hydrophobically adsorbed. As a first result, we have found that a good transfection level can be achieved simply with the neutral core particle, provided a zwitterionic lipid (dioleoyl phosphatidylethanolamine) is added to completely coat the DNA. Addition of lipids bearing a fusogenic or a nuclear localization peptide head group to the particles does not significantly improve an already efficient system, in contrast to polylysine-based gene transfer methods that rely on lysosomotropic or fusogenic agents to be effective. This emphasizes the distinctive properties of the lipopolyamines, including cell membrane destabilization, endosome buffering capacity, and possibly nuclear tropism. Most importantly, addition of lipids with a triantennary galactosyl residue drives the neutral nucleolipidic particles to the asialoglycoprotein receptor of human hepatoma HepG2 cells: Transfection increases approximately 1000-fold with 25% galactolipid. This receptor-mediated process is saturable and slightly less efficient than receptor-independent transfection obtained in vitro with a large excess of cationic lipid alone. Yet, electrically silent particles may provide an attractive solution for gene transfer in vivo where their external saccharide coat should allow them to diffuse within the organism and reach their target cells. PMID- 7878053 TI - Human RanGTPase-activating protein RanGAP1 is a homologue of yeast Rna1p involved in mRNA processing and transport. AB - RanGAP1 is the GTPase activator for the nuclear Ras-related regulatory protein Ran, converting it to the putatively inactive GDP-bound state. Here, we report the amino acid sequence of RanGAP1, derived from cDNA and peptide sequences. We found it to be homologous to murine Fug1, implicated in early embryonic development, and to Rna1p from Saccharomyces cerevisiae and Schizosaccharomyces pombe. Mutations of budding yeast RNA1 are known to result in defects in RNA processing and nucleocytoplasmic mRNA transport. Concurrently, we have isolated Rna1p as the major RanGAP activity from Sc. pombe. Both this protein and recombinant Rna1p were found to stimulate RanGTPase activity to an extent almost identical to that of human RanGAP1, indicating the functional significance of the sequence homology. The Ran-specific guanine nucleotide exchange factor RCC1 and its yeast homologues are restricted to the nucleus, while Rna1p is reported to be localized to the cytoplasm. We suggest a model in which both activities, nuclear GDP-to-GTP exchange on Ran and cytoplasmic hydrolysis of Ran-bound GTP, are essential for shuttling of Ran between the two cellular compartments. Thus, a defect in either of the two antagonistic regulators of Ran would result in a shutdown of Ran-dependent transport processes, in agreement with the almost identical phenotypes described for such defects in budding yeast. PMID- 7878054 TI - Site-directed mutagenesis studies of the high-affinity streptavidin-biotin complex: contributions of tryptophan residues 79, 108, and 120. AB - We report the functional characterization of site-directed biotin binding-site mutants of recombinant core streptavidin. The mutagenesis studies were aimed at characterizing the contributions of Trp residues known to contact biotin that have been postulated to control the exceptional binding affinity observed in this system. The functional properties of single site-directed mutants replacing Trp residues with Phe or Ala at positions 79, 108, and 120 were investigated by quantitating the EC50 binding parameters of these mutants to biotin and 2 iminobiotin in an ELISA format. The biotin EC50 for all mutants was the same as wild-type streptavidin, demonstrating that their delta Ka values relative to wild type were < 10(6). The conservative W79F and W108F mutants displayed only a 2- to 3-fold increase in EC50 for 2-iminobiotin, corresponding to an estimated delta Ka < 10, while the W120F mutant displayed a much greater alteration in 2-iminobiotin EC50, corresponding to an estimated delta Ka of 10(2). These delta Ka values are likely to reflect similar changes for biotin. The 2-iminobiotin EC50 values for the Ala mutants fell outside the accessible concentration range of the ELISA assay, demonstrating that these mutations lowered the Ka by a factor of 10(4) to 10(6). Direct estimation of biotin Ka values for W79A, W120A, and W120F in an ultrafiltration binding assay yielded Ka values of 4.3 x 10(7) M-1, 8.6 x 10(6) M 1, and > 5 x 10(9) M-1, respectively, in excellent agreement with the ELISA estimates of delta Ka with 2-iminobiotin as a reporter ligand. The results of these preliminary functional studies suggest that these aromatic side chains contribute significantly to the streptavidin-biotin binding free energy. PMID- 7878055 TI - Caveolae from luminal plasmalemma of rat lung endothelium: microdomains enriched in caveolin, Ca(2+)-ATPase, and inositol trisphosphate receptor. AB - A distinctive feature of many endothelia is an abundant population of noncoated plasmalemmal vesicles, or caveolae. Caveolae have been implicated in many important cellular processes, including transcytosis, endocytosis, potocytosis, and even signal transduction. Because caveolae have not been purified from endothelial cell surfaces, little is known directly about their structure and function in the endothelium. To delineate the transport role of these caveolae, we purified them from isolated luminal endothelial plasma membranes of rat lung. The rat lung luminal endothelial cell surfaces were isolated after coating them, in situ, with positively charged colloidal silica. The caveolae were then separated from these coated membranes and purified to yield a homogeneous population of morphologically distinct vesicles enriched in the structural protein caveolin. As with caveolae found on the endothelial cell surface in vivo, these highly purified caveolae contained the plasmalemmal Ca(2+)-ATPase and inositol 1,4,5-trisphosphate surface receptors. By contrast, other plasma membrane proteins were excluded from the caveolae, including angiotensin converting enzyme, beta-actin, and band 4.1. The purified caveolae appeared to represent specific microdomains of the cell surface with their own unique molecular topography. PMID- 7878056 TI - Molecular chaperones involved in protein degradation in the endoplasmic reticulum: quantitative interaction of the heat shock cognate protein BiP with partially folded immunoglobulin light chains that are degraded in the endoplasmic reticulum. AB - In the absence of immunoglobulin heavy-chain expression, some immunoglobulin light (L) chains are retained and degraded within the cell. We investigated the fate of two different nonsecreted murine L chains which exhibit different half lives (50 min and 3-4 hr). Our results demonstrate that both nonsecreted L chains are quantitatively bound to BiP as partially oxidized molecules. The kinetics of L-chain degradation coincided with those of L-chain dissociation from BiP, which suggests that these two processes are functionally related. L-chain degradation does not depend on vesicular transport, indicating that these soluble proteins are degraded in the endoplasmic reticulum (ER). In contrast, secreted L chains, which interact only transiently with BiP, are completely oxidized and are not degraded even when they are artificially retained in the ER. Our data support the model that, by means of BiP interaction, the ER degradation mechanism has the potential to discriminate between partially and completely folded molecules. PMID- 7878057 TI - Identification of a protein complex that is required for nuclear protein import and mediates docking of import substrate to distinct nucleoporins. AB - We have identified and characterized a 9S protein complex from a Xenopus ovary cytosolic subfraction (fraction A) that constitutes this fraction's activity in recognizing a model nuclear import substrate and docking it at the nuclear pore complex. Because of its function, the complex is termed karyopherin. The 54- and 56-kDa subunits of the complex are termed alpha 1 and alpha 2, respectively, and the 97-kDa subunit is termed beta. In an alternative approach we have identified karyopherin beta from a rat liver cytosolic subfraction A by using immobilized rat nucleoporin Nup98 in a single, affinity-based enrichment step. We have molecularly cloned and sequenced rat karyopherin beta. Comparison with protein sequence data banks showed no significant similarity to other known proteins. Using nitrocellulose-immobilized rat liver nuclear envelope proteins and nuclear import substrate as a ligand, we found Xenopus fraction A-dependent binding to at least three bona fide nucleoporins (Nup214, Nup153, and Nup98) and to a candidate nucleoporin with an estimated molecular mass of 270 kDa. We propose that these nucleoporins function as docking proteins for karyopherin-mediated binding of substrate in a nuclear import/export pathway across the nuclear pore complex. PMID- 7878058 TI - Knockout of the mouse apolipoprotein B gene results in embryonic lethality in homozygotes and protection against diet-induced hypercholesterolemia in heterozygotes. AB - Apolipoprotein B is synthesized by the intestine and the liver in mammals, where it serves as the main structural component in the formation of chylomicrons and very low density lipoproteins, respectively. Apolipoprotein B is also expressed in mammalian fetal membranes. To examine the consequences of apolipoprotein B deficiency in mice, we used gene targeting in mouse embryonic stem cells to generate mice containing an insertional disruption of the 5' region of the apolipoprotein B gene. Mice that were heterozygous for the disrupted apolipoprotein B allele had an approximately 20% reduction in plasma cholesterol levels, markedly reduced plasma concentrations of the pre-beta and beta-migrating lipoproteins, and an approximately 70% reduction in plasma apolipoprotein B levels. When fed a diet rich in fat and cholesterol, heterozygous mice were protected from diet-induced hypercholesterolemia; these mice, which constitute an animal model for hypobetalipoproteinemia, should be useful for studying the effects of decreased apolipoprotein B expression on atherogenesis. The breeding of heterozygous mice yielded no viable homozygous apolipoprotein B knockout mice. Most homozygous embryos were resorbed by midgestation (before gestational day 11.5); several embryos that survived until later in gestation exhibited exencephalus. The embryonic lethal phenotype was rescued by complementation with a human apolipoprotein B transgene--i.e., human apolipoprotein B transgenic mice that were homozygous for the murine apolipoprotein B knockout mutation were viable. Our findings indicate that apolipoprotein B plays an essential role in mouse embryonic development. PMID- 7878059 TI - Mitogenic and melanogenic stimulation of normal human melanocytes by melanotropic peptides. AB - The significance of melanotropic hormones as physiologic regulators of cutaneous pigmentation in humans is still controversial. Until recently, no direct effect for melanotropins could be demonstrated on human melanocytes. Here we present conclusive evidence that alpha-melanotropin (alpha-melanocyte-stimulating hormone, alpha-MSH) and the related hormone corticotropin (adrenocorticotropic hormone, ACTH) stimulate the proliferation and melanogenesis of human melanocytes maintained in culture in a growth medium lacking any AMP inducer. The minimal effective dose of either hormone is 0.1 nM. In time-course experiments, the increase in cell number and tyrosinase activity became evident after one treatment of the melanocytes with 100 nM alpha-MSH for 48 hr. The mitogenic effect gradually increased to 50-270% above control, depending on the individual melanocyte strain, with continuous treatment with 100 nM alpha-MSH for 8 days, whereas the melanogenic effect became maximal (70-450% increase above control) after 4 days of treatment. Western blot analysis of tyrosinase and the tyrosinase related proteins TRP-1 and TRP-2 revealed that alpha-MSH increased the expression of those three melanogenic proteins. This was not accompanied by any change in their mRNA levels after brief (1.5-24 hr) or prolonged (6 days) treatment with 100 nM alpha-MSH, suggesting that the increased expression of these melanogenic proteins was due to posttranscriptional events. These results demonstrate both mitogenic and melanogenic effects of alpha-MSH and ACTH on human melanocytes. That both hormones are effective at subnanomolar concentrations, combined with the presence of melanotropin receptors on human melanocytes, strongly suggests that these melanotropins play a physiologic role in regulating human cutaneous pigmentation. PMID- 7878060 TI - Biochemical and molecular aspects of mammalian susceptibility to aflatoxin B1 carcinogenicity. AB - Aflatoxin B1 (AFB1) is a fungal toxin that has been implicated as a causative agent in human hepatic and extrahepatic carcinogenesis. In this review, the mechanisms involved in AFB1 toxicity are delineated, in order to describe the features that make a specific cell, tissue, or species susceptible to the mycotoxin. Important considerations include: (i) different mechanisms for bioactivation of AFB1 to its ultimate carcinogenic epoxide metabolite; (ii) the balance between bioactivation to and detoxification of the epoxide; (iii) the interaction of AFB1 epoxide with DNA and the mutational events leading to neoplastic transformation; (iv) the role of cytotoxicity in AFB1 carcinogenesis; (v) the significance of nonepoxide metabolites in toxicity; and (vi) the contribution of mycotoxin-unrelated disease processes. Although considerable controversy remains about the importance of specific events, a great deal has been learned about biochemical and molecular actions of AFB1. PMID- 7878062 TI - The developing role of magnetic resonance contrast media in the detection of ischemic heart disease. AB - Recent developments in magnetic resonance (MR) imaging have opened up new avenues in the investigation of cardiovascular physiology. Inherent signal intensity of any tissue on MR images depends largely on proton concentration as well as longitudinal (T1) and transverse (T2) relaxation times. Myocardial contrast can be manipulated by using specific MR pulse sequences which are selectively sensitive to differences in any one of these parameters. Paramagnetic metal complexes are used as contrast media in MR imaging to enhance the inherent contrast. Contrast media in MR imaging are not directly visible but change the magnetic properties of other nuclei in close proximity, such as those of the water hydrogen. The signal of water can be altered by the contrast medium in different ways, either by changing the relaxation times or through bulb susceptibility effects, or both. The role of MR contrast media for quantitative characterization of ischemic heart disease has advanced considerably in the past 10 years. Conventional MR imaging techniques following the administration of contrast media are useful for identifying and sizing myocardial infarctions and for distinguishing between occlusive and reperfused myocardial infarctions as well as reversible (stunned) and irreversible injuries. Recent results suggest that contrast-enhanced MR imaging can also be used to identify dead cells in reperfused ischemically injured myocardium. The recently developed fast MR imaging techniques, with the aid of MR contrast media as a perfusion indicator, may be useful in estimating regional myocardial perfusion and blood volume. The assessment of capillary circulation or myocardial perfusion may be used for evaluating the extent of hypoperfusion and treatment efficacy. Experimental and clinical perfusion studies indicate that perfusion-sensitive MR imaging detects compromised myocardium (area at risk). Combining myocardial perfusion imaging with the anatomic and functional information provided by other MR imaging sequences could make MR imaging a comprehensive noninvasive technique for the evaluation of ischemic heart disease. PMID- 7878063 TI - Calcium-sensitive chloride channels in vascular smooth muscle cells. AB - Chloride (Cl-) channels were characterized in vascular smooth muscle cells (VSMC) using radioisotope flux and patch-clamp electrophysiological techniques. Transmembrane 125iodine (125I) efflux from subcultured (Passage 1-5) rat aortic VSMCs was used as an indicator of Cl- movements to study the relationship between intracellular calcium concentration ([Ca2+]i) and Cl- channel activity. Angiotensin II (Ang II) (10(-7) M) and adenosine 5'-triphosphate (ATP) (10(-4) M) induced rapid increases (9.7- and 14.9-fold, respectively) in 125I efflux rates. We found that both Ang II- and ATP-stimulated 125I efflux and [Ca2+]i increases were completely abolished after brief incubation (20 microM, 20 min) with the acetoxymethyl ester of 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), a membrane-permeable Ca2+ chelator. However, when external EGTA was used to blunt agonist-stimulated Ca2+ influx, 125I efflux was still increased in response to Ang II and ATP. These data suggest that Ca2+ release from intracellular sites is sufficient to activate Cl- channels in response to Ang II and ATP. Using standard patch-clamp electrophysiological techniques, we found that Ang II, a Ca(2+)-mobilizing agonist, stimulated outward Cl- currents (gCl = 75 pS) in cell-attached (C/A) patches of primary and subcultured VSMCs. Collectively, these data suggest that Ang II and other vasoconstrictor agents stimulate Cl- channel activity via increases in [Ca2+]i. Cl- channel activation may help to depolarize the VSMC membrane leading to increased Ca2+ influx during agonist stimulation. PMID- 7878061 TI - Use of top-down elasticity analysis to identify sites of thyroid hormone-induced thermogenesis. AB - Top-down elasticity analysis is a novel extension of top-down metabolic control analysis. It has provided researchers with a theoretical and practical platform upon which quantitative analyses of the sites of action of hormones and drugs can be based. This approach is easy to apply and involves dividing up the metabolic system in question into two or three blocks of enzyme reactions around an intermediate between the blocks of reactions. The kinetic response of each block to the intermediate is measured in the steady state in situ by determining the flux through the block at different measured intermediate concentrations. The intermediate can be manipulated by titrating the other blocks with suitable inhibitors or activators. Then, to determine which blocks of reactions are quantitatively the most important in terms of any change in the flux rate of the system, a quantitative comparison of the titration curves from the experimental preparations is made with those of the control preparations. In this minireview we will examine, as an example, the use of top-down elasticity analysis for the quantitative identification of the important sites of action of thyroid hormones on oxidative phosphorylation in hepatocytes. The experimental results show that approximately 50% of the change in resting oxygen consumption in hepatocytes from hypothyroid and hyperthyroid rats (compared with euthyroid controls) is attributable to changes in the rate of the mitochondrial proton leak; the remaining 50% is accounted for by changes in nonmitochondrial- and ATP turnover dependent oxygen consumption in hypothyroid and hyperthyroid hepatocytes, respectively. PMID- 7878065 TI - Effects of macrophage supernatants on mesangial cell migration and hillock formation. AB - There is considerable evidence suggesting a role for the macrophage (M phi) in the development of glomerulosclerosis (GS) and atherosclerosis, lesions which appear to be analogous. Migration of mesangial cells (MC), which are modified smooth muscle cells, may play a role in the pathogenesis of glomerular injury, and smooth muscle migration may play a role in the pathogenesis of atherosclerosis as well. We undertook the present study to determine the effects of M phi supernatants (M phi SN) on MC migration and formation of MC hillocks, which are considered an in vitro model of GS. By means of a migration assay using wounded cultures of confluent, growth-arrested MC, MC migration was found to be significantly enhanced by incubation with M phi SN at 24 hr (migration score: M phi SN, 24.3 +/- 1.3; control, 11.6 +/- 1.0, P < 0.001) as well as 48 hr incubation (migration score: M phi SN, 34.0 +/- 1.4; control, 15.4 +/- 1.4, P < 0.001). Enhanced MC migration following prolonged incubation with M phi SN was also shown using phase contrast microscopy and scanning electron microscopy. MC hillock formation was enhanced by M phi SN in a concentration-related manner as was hillock size. These data demonstrate that M phi SN can directly enhance MC migration and hillock formation, processes that may in part account for the observed role for the M phi in the development of mesangial expansion and GS as well as atherosclerosis. PMID- 7878064 TI - Mitochondrial aspartate aminotransferase expressed on the surface of 3T3-L1 adipocytes mediates saturable fatty acid uptake. AB - Physicochemical studies have suggested that the 43-kDa plasma membrane fatty acid binding protein (FABPpm) is closely related to the mitochondrial isoform of aspartate aminotransferase (mAspAT). In the present studies, mAspAT was not detected immunohistochemically or by immunoblotting in plasma membranes of proliferating 3T3-L1 fibroblasts. During controlled differentiation to an adipocyte phenotype, mAspAT became detectable by the second day of confluent growth, prior to accumulation of visible lipid droplets, and was strongly expressed in 8-day differentiated 3T3-L1 adipocytes. The pattern of expression paralleled the previously reported expression both of FABPpm and of the Vmax for saturable uptake of long chain free fatty acids. As with anti-FABPpm, antibodies to mAspAT selectively inhibited the uptake of [3H]-oleate in 3T3-L1 adipocytes but not in fibroblasts, while having no effect on uptake of either 2-deoxyglucose or the medium chain fatty acid octanoate. Preabsorption of anti-FABPpm with mAspAT, or of anti-mAspAT with FABPpm, abolished immunopositivity in immunohistochemical and immunoblotting studies, as well as the ability of either antibody to inhibit [3H]-oleate uptake. These studies provide strong biologic evidence for the identity of FABPpm and mAspAT, and for the hypothesis that FABPpm/mAspAT mediates the uptake of long chain free fatty acids. PMID- 7878066 TI - Genetic variation in plasma androgens and ovarian aromatase activity during mouse pregnancy. AB - Genetic variation in fetal survival, maternal plasma androgen levels, and ovarian aromatase activity was examined mid (Day 9) and late gestation (Day 16) in strains of mice that differ in reproductive performance (A/J, C57BL/6J, C8/JIs, C17/JIs, and S15/JIs). At both gestational stages, females selected for large litter size (S15/JIs) carried more fetuses than any of the other strains examined. Particularly at midpregnancy, S15/JIs females also maintained higher plasma levels of androstenedione and testosterone relative to both control strains, C8/JIs and C17/JIs. Consistent with previously reported changes in peripheral estrogen levels during mouse pregnancy, aromatase activity was higher on Day 16 than on Day 9. This study demonstrates genetic variation in fetal survival that is correlated with increased maternal androgen levels. A stage specific gestational increase in aromatase activity occurs in several strains of mice and is associated with elevated plasma estrogen during the second half of pregnancy. PMID- 7878067 TI - Comparison of the ability of normal mouse mammary tissues and mammary adenocarcinoma to cleave rat prolactin. AB - Previous studies have shown that target tissues cleave rat prolactin (rPRL) to form a two-chain derivative that yields approximately 16- and approximately 6-kDa fragments upon reduction. Both cleaved rPRL and the purified 16-kDa fragment have novel biological activities. Thus, cleavage may be of physiological significance. We determined whether normal mammary tissue or stroma (lacking mammary epithelial cells [MEC]) or mammary tumor tissue could cleave rPRL in vitro. Tumor explants were derived from a transplantable mammary tumor cell line (TPDTMT-4EP). The hormone was incubated with explants of those tissues from female BALB/c or DDD mice. Medium samples were processed by SDS-PAGE, and the relative abundance of intact and cleaved rPRL was determined by densitometric analysis of immunoblots using an antiserum to the 16-kDa fragment of rPRL. After 2-hr of incubation, normal DDD mammary explants cleaved approximately 25% of added rPRL, but tumor explants cleaved none. Explants of intact virgin BALB/c mouse mammary gland and of parenchyma-free "cleared" mammary fat pad cleaved rPRL equally well, but explants of abdominal adipose tissue had low cleaving activity. Homogenates of cleared mammary fat pads that were incubated with rPRL contained a high proportion of the cleaved form but none of the free 16-kDa fragment. These results indicate that cleavage of rPRL is highly specific to mammary stroma. Such cleavage may yield a form of the hormone that has novel activities within the mammary gland or elsewhere in the body. PMID- 7878068 TI - Administration of a perfluorochemical emulsion plus carbogen breathing does not alter radiation pneumonitis. AB - The effects of treatment with a perfluorochemical emulsion plus carbogen on radiation pneumonitis were examined in a rat model system. Rats received thoracic irradiation (15 Gy) and radiation reactions in the lungs were assessed 25 and 35 days later using bronchoalveolar lavage and histologic assessments. The irradiated lungs showed the expected evidence of acute radiation pneumonitis, including protein leaks and also alveolar infiltrates and interstitial infiltrates. Administration of a perfluoro-chemical emulsion (Fluosol; 15 ml/kg) plus carbogen breathing for 30 min before and during irradiation did not enhance the reactions seen in the irradiated lungs. PMID- 7878069 TI - Probable immune system mediation of the antitumor activity of the 2,6 dimethoxybenzo-p-semiquinone radical. AB - We recently reported that the antitumor activity of an immobilized oxidase peroxidase system, which can produce radical species as intermediates, is dependent on the presence of an intact and functioning immune system in the host. A number of recent investigations have indicated that the bioactive form of many quinone-type anticancer agents may be the semiquinone-type radical. To investigate if the antitumor activity of some of the quinone-type anticancer agents may also be dependent on a fully functioning immune system in the host, we used as a simple, well-defined model the 2,6-dimethoxybenzo-p-semiquinone radical. This free radical has a potent antitumor activity against Ehrlich ascites tumors in mice, as first described by Szent-Gyorgyi's group. In the present study, we investigated its antitumor activity in immunocompromised BALB/c mice. We found that the antitumor activity of the semiquinone radical is completely abolished in mice that had previously been subjected to whole body gamma irradiation, indicating a possible involvement of one or more cells of the host's defense system. The antitumor activity was not abolished in mice with dysfunctional macrophages induced by a severe selenium deficiency. However, the radical was inactive in mice whose immune system was suppressed with cyclosporin A and in nude (nu/nu) mice. These results suggest that the dimethoxybenzo semiquinone radical, rather than acting primarily as a cytotoxic agent as previously reported, exerts its antitumor activity mainly via a more complex mechanism in which T lymphocytes appear to play a major role. PMID- 7878070 TI - Effects of streptozotocin-induced diabetes and insulin treatment on blood pressure in the male rat. AB - Hyperinsulinemia may link diabetes to hypertension. We evaluated the effects of insulin on blood glucose and blood pressure in control and streptozotocin (STZ) induced (60 mg/kg, i.v.) diabetes. Insulin was given daily for 10-14 weeks to both diabetic (0, 1, 2, and 3 U) and control (0, 2, and 3 U) male rats (n = 7 8/group). Indirect and direct blood pressures were measured as were blood glucose and several metabolic parameters. All treated rats became hyperinsulinemic. Untreated and 1 U insulin-treated diabetic rats were hyperglycemic. Higher doses of insulin significantly reduced blood glucoses in diabetic animals. Indirect blood pressure measurements were unchanged between groups. However, when measured directly, the untreated diabetic rats had significantly lower pressures that did untreated controls. Insulin treatment at dosages above 1 U normalized blood pressure in diabetic animals. These same doses of insulin also restored to normal all the metabolic parameters associated with diabetes. Insulin treatment did not affect any of the parameters evaluated in nondiabetic rats. Collectively, the results show that STZ-induced diabetes results in a decrease in blood pressure and that insulin treatment can restore blood pressure in diabetic rats. Although the results suggest that insulin may be involved in restoring blood pressure in animals with a carbohydrate imbalance, the precise mechanism for elevating blood pressure is not known with certainty. PMID- 7878071 TI - The effects of phytoestrogens on neonatal rat uterine growth and development. AB - Phytoestrogens found in clover, alfalfa, and soybeans have caused reproductive toxicity in several mammalian species. Other estrogens, such as diethylstilbestrol (DES), are developmental toxicants, reducing uterine estrogen receptor (ER) concentration, altering uterine growth, and eliciting reproductive tract abnormalities in the rat. The present study examines the effects of the phytoestrogens coumestrol and equol on the developing rat uterus. Various doses of these compounds were injected sc on postnatal days (PND) 1-5 or 1-10 to ascertain their effects on uterine weight and ER levels, and on PND 10-14 to determine their effects on uterine weight and gland genesis. Coumestrol (PND 1-5) was about 10(-3) as potent as DES in increasing uterine weight (wet or dry) while equol increased dry weight only, with a potency of 10(-5) that of DES. Although the 10 and 100 micrograms doses of coumestrol (PND 1-5 or 1-10) initially increased uterine wet weight, by PND 20 uterine weights either equaled or fell significantly below controls. The 100-micrograms dose of coumestrol (PND 1-5 or 1 10) reduced ER levels at all ages, while the 10-micrograms dose was not as effective. Equol (PND 1-5 or 1-10) did not affect ER levels. Premature uterine gland genesis occurred by PND 9 for the PND 1-5 100-micrograms coumestrol dose. When given on PND 10-14 (the critical period of gland genesis), 10 micrograms and 100 micrograms of coumestrol and 10 micrograms DES greatly increased uterine weight, while no effect was elicited by equol. Although coumestrol and equol inhibited uterine gland genesis in a dose-dependent manner, neither abolished gland genesis as did 10 micrograms of DES or tamoxifen. These data demonstrate that coumestrol elicits uterine biochemical and morphological toxicity much like DES. Equol decreased uterine gland number without increasing uterine wet weight or luminal epithelial hypertrophy, which is inconsistent with either an estrogenic or antiestrogenic action in the uterus. PMID- 7878072 TI - Cardiac noradrenergic mechanisms mediate GABA-enhanced ouabain cardiotoxicity. AB - Peripherally administered gamma-aminobutyric acid (GABA) alters cardiovascular function and has been reported to enhance ouabain-induced cardiotoxicity in vivo. Control and reserpinized rat hearts were perfused in vitro to determine if GABA directly evokes bradycardia by GABAA receptors, interacts with ouabain, and if noradrenergic mechanisms are required. Also, double-staining immunohistochemistry was employed to determine whether GABA-ergic and noradrenergic synthetic enzymes were juxtaposed within atrial tissue. The main results were as follows. GABA produced a dose-dependent bradycardia (p < 0.05) by stimulating GABAA receptors in Langendorff-perfused hearts. Reserpinized hearts were unresponsive (p < 0.05) to GABA, except at the highest dose (20 mg/ml). Ouabain-induced cardiotoxicity was enhanced (p < 0.05) by GABA in isolated control, but not reserpinized hearts. Lastly, glutamic acid decarboxylase and tyrosine hydroxylase immunoreactivities were in close proximity in atrial slices. Collectively, the results document that GABA causes bradycardia and enhances ouabain cardiotoxicity by modulating noradrenergic mechanisms in the isolated rat heart. Since the synthetic enzymes for GABA and norepinephrine were in close proximity in atrial tissue, these transmitters may interact under physiological conditions. PMID- 7878073 TI - Effect of chronic treatment with prazosin and L-arginine on the elevation of blood pressure during cold exposure. AB - Chronic exposure to cold (5 degrees C) is well known to increase both tyrosine hydroxylase (TH) activity in brown adipose tissue and systemic blood pressure. The effect of chronic dietary administration of the alpha-adrenergic antagonist, prazosin, and the amino acid, L-arginine, on both the elevation of blood pressure during exposure to cold and on TH activity and expression of TH mRNA in the adrenal glands of rats was studied. As observed previously, chronic exposure to cold increased systolic blood pressure significantly and induced cardiac hypertrophy. Chronic dietary treatment with prazosin (8 mg/kg food) and arginine (20 g/kg food) returned blood pressure to control levels, did not affect body weight significantly, but failed to prevent cardiac hypertrophy. Both prazosin and L-arginine reduced the drinking response to administration of angiotensin II. Treatment with arginine and prazosin was accompanied by a significant increase in the urinary outputs of dopamine and L-DOPA. The 3 cold-treated groups (control, L arginine and prazosin) had increases in plasma T3 and decreases in plasma T4 and plasma renin activity. Plasma concentrations of epinephrine and norepinephrine were increased significantly in the L-arginine-treated group. TH mRNA and TH activity in the adrenal glands were increased in the 3 cold-treated groups and these measures were correlated directly and significantly with plasma norepinephrine and epinephrine concentrations. Although both prazosin and arginine prevented the cold-induced elevation of blood pressure, they did not prevent the increase in TH mRNA, TH activity or epinephrine in plasma. The protective effect of arginine and prazosin in cold-induced hypertension may be related both to their reduction in plasma renin activity and to a reduced responsiveness to angiotensin II, as well as to their abilities to increase the secretion of dopamine. PMID- 7878074 TI - Selective in vivo antagonism of pinacidil-induced hypotension by the guanidine U37883A in anesthetized rats. AB - The pyridylcyanoguanidine pinacidil exerts its hypotensive effect by opening ATP sensitive potassium channels (K+ATP) in vascular smooth muscle. Direct glyburide like antagonism of pinacidil-induced vasorelaxation by the guanidine U37883A (4 morpholinecarboximidine-N-1-adamantyl-N'- cyclohexylhydrochloride) has recently been demonstrated in isolated rabbit mesenteric artery. We herein report the first detailed in vivo cardiovascular interaction between U37883A and pinacidil in an anesthetized rat model. U37883A, administered from 0.1 to 3.0 mg/kg i.v. 10 min subsequent to pinacidil, immediately and dose-dependently reversed pinacidil's steady-state hypotensive effects by 29-100% (ED50 = 0.4 mg/kg), while reversal of pinacidil's tachycardiac effects from 10 to 79% was evident with 0.1 1.0 mg/kg i.v. U37883A (ED50 = 0.5 mg/kg). In contrast to these effects, pretreatment with 0.3-3.0 mg/kg i.v. U37883A only moderately inhibited the acute pinacidil-induced hypotension by 6-58%. Because U37883A's separate bradycardiac effects lowered basal heart rate, U37883A pretreatment precipitated a paradoxical 15-51% augmentation of sustained pinacidil-induced tachycardia, although absolute heart rates were below those seen with pinacidil alone. Qualitatively similar K+ATP blocking effects by U37883A were also observed in rats treated with the K+ATP openers (PCOs) cromakalim (BRL 34915), RPS 49365 and minoxidil. However, U37883A-treated rats remained responsive to the hypotensive action of both i.v. sodium nitroprusside and isoproterenol and buccal nifedipine. This study corroborates prior in vitro and in vivo findings and establishes that the guanidine U37883A is an effective and relatively selective blocker of PCO-induced vasodilation in the anesthetized rat. U37883A also appears more effective at closing basally and pinacidil-opened K+ATP than preventing K+ATP opening by pinacidil in vivo. PMID- 7878075 TI - Beneficial effects of BAY u3405, a novel thromboxane A2 receptor antagonist, in splanchnic artery occlusion shock. AB - Splanchnic artery occlusion shock was induced in male anaesthetized rats by clamping the splanchnic artery for 45 min. The arteries were then released and survival rate, mean survival time, mean arterial blood pressure, plasma levels of thromboxane B2 and 6-keto-PGF1 alpha, macrophage phagocytosis activity and plasma levels of myocardial depressant factor were evaluated. In addition, the neutrophilic infiltrate was quantified in the ileum and lung using a myeloperoxidase (MPO) assay. Sham splanchnic-artery-occlusion-shocked rats were used as controls. Splanchnic-artery-occlusion-shocked rats died within 93 +/- 7 min, while all sham-shocked animals survived more than 3 h. Splanchnic artery occlusion shock caused changes in mean arterial blood pressure, significantly increased the plasma levels of thromboxane B2 (7.5 +/- 1.3 ng/ml; p < 0.001 vs. sham), 6-keto-PGF1 alpha (8.9 +/- 1.7 ng/ml; p < 0.001 vs. sham) and myocardial depressant factor (114 +/- 11 U/ml), and reduced macrophage phagocytosis. Furthermore, MPO activity was significantly elevated (0.12 +/- 0.03 x 10(-3) and 1.8 +/- 0.5 x 10(-3) U/g protein in the ileum and lung, respectively) 70 min after starting reperfusion. Administration of BAY u3405, a novel thromboxane A2 receptor antagonist (30 mg/kg i.v., 30 min before occlusion), significantly increased survival time (187 +/- 3.7 min) and survival rate, improved mean arterial blood pressure, reduced the plasma levels of myocardial depressant factor (54 +/- 3 U/ml), partially restored macrophage phagocytosis and lowered MPO activity in both the ileum and the lung. Our data are consistent with an involvement of thromboxane A2 in splanchnic artery occlusion shock and suggest that BAY u3405 might be of benefit in low-flow states such as circulatory shock. PMID- 7878076 TI - Effect of chronic ethanol consumption on the pharmacological response of the rabbit corpus cavernosum. AB - Previous studies demonstrated that acute in vitro exposure of corpus cavernosal tissue to ethanol decreased its response to field stimulation and pharmacological stimulation. In the current study the effects of chronic ethanol consumption on the responses of the rabbit corpus cavernosum to field stimulation and various autonomic agonists were investigated. Five percent (V/V) ethanol in drinking water was given to rabbits for 6 weeks. At the end of this time the in vitro response of the corpus cavernosum to various forms of stimulation was determined. The corporal smooth muscle taken from rabbits subjected to chronic ethanol consumption demonstrated the following characteristics compared to tissue taken from control rabbits. (1) Under basal conditions, both relaxation and contraction induced by field stimulation were significantly increased. (2) Contractions to both phenylephrine and KCl increased significantly. (3) In the tissue preincubated with phenylephrine, relaxations induced by field stimulation, ATP, and bethanechol were significantly enhanced. (4) The relaxation responses to sodium nitroprusside were not changed by chronic exposure to ethanol. These findings suggest that in vivo chronic ethanol administration augmented both stimulated contracation and stimulated relaxation of the corporal smooth muscle. PMID- 7878078 TI - Ethnopharmacology in the Brazilian Amazon. AB - The potential pharmaceutical wealth of the Brazilian Amazon has attracted international attention from the general and scientific community. The role that ethnopharmacology can have in the discovery and development of new drugs from a region hosting such enormous cultural and biological diversity is discussed. A review is given of ethnopharmacological and ethnobotanical studies that have been conducted in the Brazilian Amazon over the past twenty years. PMID- 7878077 TI - Theophylline attenuates circulating vitamin B6 levels in children with asthma. AB - This study was undertaken to investigate the effect of theophylline on circulating vitamin B6 levels in children with asthma. Twenty-six asthmatic children, including 20 patients who were treated with slow-release theophylline and 6 patients not receiving any type of theophylline preparation, were enrolled in this study. Steady state serum theophylline and vitamin B6 [pyridoxal 5' phosphate (PLP) and pyridoxal (PL)] levels were evaluated in these patients. A depression of serum PLP levels existed in asthmatic children treated with theophylline compared to those not receiving theophylline (5.3 +/- 0.5 vs. 9.0 +/ 1.4 ng/ml, mean +/- SEM; p < 0.05). A significant negative correlation between the serum levels of PLP and theophylline was demonstrated in the subjects of this study (rs = -0.609, p < 0.001). Oral administration of 200 mg of theophylline (TheoDur) to 5 children with asthma significantly depressed serum PLP levels 4 h after the drug intake (p < 0.05), whereas theophylline did not affect serum PL levels. From these results, we conclude that theophylline induces a depression of circulating PLP levels in asthmatic children. PMID- 7878080 TI - Kirin International Symposium on Bitter Taste. Tokyo, Japan, October 3-5, 1993. PMID- 7878079 TI - Dopamine receptors: molecular biology, biochemistry and behavioural aspects. AB - The description of new dopamine (DA) receptor subtypes, D1-(D1 and D5) and D2 like (D2A, D2B, D3, D4), has given an impetus to DA research. While selective agonists and antagonists are not generally available yet, the receptor distribution in the brain suggests that they could be new targets for drug development. Binding characteristics and second messenger coupling has been explored in cell lines expressing the new cloned receptors. The absence of selective ligands has meant that in vivo studies have lagged behind. However, progress has been made in understanding the function of DA-containing discrete brain nuclei and the functional consequence of the DA's interaction with other neurotransmitters. This review explores some of the latest advances in these various areas. PMID- 7878081 TI - Receptor mechanisms of bitter substances. AB - The receptor mechanism of bitter substances was discussed from the following points of views. (a) Both electrostatic and hydrophobic interactions of bitter substances with taste receptor membranes contribute to reception of bitter substances having a positive charge. (b) In the frog, the responses to bitter substances are easily adapted. The presence of Ca ion in the medium prolongs the responses. (c) Bitter substances elicit electrical responses in nongustatory cells such as neuroblastoma cells and olfactory cells, suggesting that bitter substances induce the response by nonreceptor-mediated mechanism. (d) There is also a possibility that receptors for some bitter substances are G-protein coupled. We cloned G-protein coupled receptors from bovine taste tissues. (e) A specific inhibitor of bitter taste has been desired in pharmaceutical and food sciences, but it has not been available. We found that a lipoprotein made of phosphatidic acid and beta-lactoglobulin selectively inhibits the responses to bitter substances in the frog and humans. Binding of the lipoprotein to the receptor sites for bitter substances leads to suppression of the response. PMID- 7878082 TI - Receptor potential of the frog taste cell in response to bitter stimuli. AB - Molecular mechanisms of generation of the receptor potential in the bullfrog taste cell for bitter stimuli were investigated with an intracellular recording technique. During generation of the receptor potential in response to bitter stimuli, the input resistance of the taste cell increased slightly. We could not find the reversal potential for the depolarizing receptor potential induced by quinine-HCl(Q-HCl). The Q-HCl-induced response was increased with decreasing Cl- concentration in the superficial fluid. The Q-HCl response was greatly reduced by interstitial furosemide, as a blocker of Na+/Cl- cotransport, indicating that a Na+/Cl- cotransport occurs through the basolateral membrane of Q-HCl sensitive taste cells. Therefore it is concluded that the receptor potential for Q-HCl stimulation is produced by an active secretion of intracellularly accumulated Cl- through Cl- pumps of the apical receptive membrane. PMID- 7878083 TI - Genetics of bitter perception in mice. AB - Inbred and congenic strains exhibited several patterns of relative sensitivity to bitter tastants in 48-h, two-bottle preference tests. With segregation analyses of descendents of crosses between contrasting strains, these patterns suggested at least three genetic loci influencing bitter perception. The extensively characterized Soa (sucrose octaacetate) locus underlies one pattern. Variation at this locus had pleiotropic effects on avoidance of other acetylated sugars, plus such structurally dissimilar bitter tastants as brucine, denatonium benzoate, and quinine sulfate. Unlike SOA, however, sensitivity to quinine sulfate was polygenically determined, and produced a second characteristic pattern. At least one, possibly several, additional unlinked loci contributed to quinine differences. Phenylthiocarbamide (PTC) aversion differences exemplified a third pattern. Segregation consistent with monogenic control of PTC aversion has been reported, and within segregating populations PTC aversion did not covary with SOA or quinine sulfate avoidance. Variants of the three major patterns may be useful for analysis of specific mechanisms. While both showed the SOA pattern, strychnine differences were markedly smaller than brucine (dimethoxystrychnine) differences. Likewise, a hop extract containing primarily iso-alpha acids (e.g., isohumulone) produced an SOA-like pattern, while an extract with nonisomerized alpha-acids (e.g., humulone) did not. PMID- 7878084 TI - Generation of inositol phosphates in bitter taste transduction. AB - It is probable that there is a diversity of mechanisms involved in the transduction of bitter taste. One of these mechanisms uses the second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Partial membrane preparations from circumvallate and foliate taste regions of mice tongues responded to the addition of known bitter taste stimuli by increasing the amount of inositol phosphates produced after 30 s incubation. Addition of both the bitter stimulus, sucrose octaacetate and the G-protein stimulant, GTP gamma S, led to an enhanced production of inositol phosphates compared with either alone. Pretreatment of the tissue samples with pertussis toxin eliminated all response to sucrose octaacetate plus GTP gamma S, whereas pretreatment with cholera toxin was without effect. Western blots of solubilized tissue from circumvallate and foliate regions probed with antibodies to the alpha-subunit of several types of G proteins revealed bands reactive to antibodies against G alpha i1-2 and G alpha o, with no apparent activity to antibodies against G alpha i3. Given the results from the immunoblots and those of the toxin experiments, it is proposed that the transduction of the bitter taste of sucrose octaacetate in mice involves a receptor-mediated activation of a Gi-type protein which activates a phospholipase C to produce the two second messengers, IP3 and DAG. PMID- 7878086 TI - PTC/PROP tasting: anatomy, psychophysics, and sex effects. AB - Taste worlds of humans vary because of taste blindness to phenylthiocarbamide (PTC) and its chemical relative, 6-n-propylthiouracil (PROP). We review early PTC studies and apply modern statistical analyses to show that a higher frequency of women tasted PTC crystals, and were tasters (threshold classification). In our laboratory, scaling of PROP bitterness led to the identification of a subset of tasters (supertasters) who rate PROP as intensely bitter. Supertasters also perceive stronger tastes from a variety of bitter and sweet substances, and perceive more burn from oral irritants (alcohol and capsaicin). The density of taste receptors on the anterior tongue (fungiform papillae, taste buds) correlate significantly with perceived bitterness of PROP and support the supertaster concept. Psychophysical data from studies in our laboratory also show a sex effect; women are supertasters more frequently. The anatomical data also support the sex difference; women have more fungiform papillae and more taste buds. Future investigations of PTC/PROP tasting and food behaviors should include scaling to identify supertasters and separate sex effects. PMID- 7878085 TI - Molecular cloning of G proteins and phosphodiesterases from rat taste cells. AB - To identify and characterize those proteins involved in taste transduction, we cloned G proteins and phosphodiesterases from rat taste tissue. Using degenerate primers corresponding to conserved regions of G protein alpha subunits, the polymerase chain reaction was used to amplify and clone eight distinct cDNAs: alpha i-2, alpha i-3, alpha 12, alpha 14, a(s), alpha t-rod, alpha t-cone and alpha gustducin. alpha i-3, alpha 14, alpha s, and alpha t-rod are more highly expressed in taste tissue than in the surrounding nonsensory tissue. alpha gustducin is only expressed in taste cells. Rod transducin had previously been found only in the rod cells of the retina, where it converts light stimulation of rhodopsin into activation of cGMP phosphodiesterase. The primary sequence of alpha gustducin shows striking similarities to rod transducin in the receptor interaction domain and the phosphodiesterase activation site. We propose that gustducin and transducin regulate phosphodiesterase activity in taste cells and that this may promote bitter transduction and inhibit sweet transduction. Consistent with this proposal, we cloned two types of cAMP PDE from taste tissue: dnc-1 and PDE-3. PMID- 7878087 TI - Denatonium bitter tasting among transgenic mice expressing rat von Ebner's gland protein. AB - Von Ebner's gland protein (VEGP) is a secretory protein, which is abundantly expressed in the small von Ebner's salivary glands of the tongue. VEGP as component of the perireceptor environment around taste papillae might function as transporter of hydrophobic molecules, for example bitter substances. Here we report a new approach to investigate the physiological role of VEGP by expression of the cloned rat VEGP gene in transgenic mice. Taste papillae of mice, in contrast to rats, do not contain VEGP. The founder mouse 4345 and three offspring carry the transgene as shown by PCR analysis and saliva of the transgenic mice contains high amounts of VEGP. In two-bottle preference tests, transgenic and nontransgenic siblings show significantly different capabilities to taste the bitter compound denatonium benzoate at 10 microM. The reduced sensitivity of transgenic mice to denatonium benzoate points to a clearance function of VEGP the specificity of which for taste compounds and other molecules remains to be seen. PMID- 7878088 TI - Glossopharyngeal denervation alters responses to nutrients and toxic substances. AB - Functional roles of the glossopharyngeal (GL) nerve on food and fluid intake were studied by examining effects of the GL denervation on two biologically different activities induced by specific diets using mice and rats. First, we examined whether GL section alters the acceptability of a bitter tasting essential amino acid, L-lysine (Lys), by Lys-deficiency in mice. The aversion threshold for Lys, normally about 3 uM in mice, increased to about 300 uM when mice were fed the Lys deficient diet for 10 days. This increase of the Lys aversion threshold (increase of acceptability for Lys) by Lys-deficiency was also evident in mice with the chorda tympani denervation but was not observed in mice with the GL denervation. Next, we examined whether GL section alters the induction of a salivary protein, cystatin S (a cysteine proteinase inhibitor), by a diet containing papain (a cysteine proteinase) in rats. GL denervation largely inhibited the induction of cystatin S in the rat submandibular glands by papain. These results collectively suggest that chemosensory information conveyed by the GL nerve plays important roles on recognition of both nutrient and toxic compounds in the diet and induction of biological responses that protect the animal from both nutritional deficiency and exogenous toxic compounds. PMID- 7878089 TI - Bitter taste in single chorda tympani taste fibers from chimpanzee. AB - We have found earlier that chimpanzee chorda tympani taste fibers fall into groups that conform with the human taste qualities. This study focuses on bitter taste and its relation to sweet taste. Eight fibers were classified as bitter fibers according to their responses to 31 stimuli. The stimuli included the bitter compounds quinine, denatonium benzoate and caffeine. The results indicate a clear dichotomy between the bitter and sweet fibers. Sweet fibers never responded to the bitter compounds. However, in addition to their responses to the above compounds, some of the bitter fibers were stimulated by other compounds. Most prominent were responses to NaCl-amiloride mixture, KCl and xylitol. In most cases the cause could be assumed to be a bitter taste in the compound. These results suggest that the bitter and sweet tastes are conveyed in specific and separate groups of nerve fibers in the chimpanzee. Because of the closeness between chimpanzee and human, this finding has implications on the question of taste coding in human and the concept of taste qualities. PMID- 7878090 TI - Neural coding of aversive and appetitive gustatory stimuli: interactions in the hamster brain stem. AB - There is increasing evidence, both electrophysiological and behavioral, that bitter and sweet stimuli drive parallel pathways in the gustatory brainstem. Here we report two lines of investigation that suggest significant interactions among these parallel systems. First, responses recorded from single cells in the hamster's parabrachial nuclei (PbN) show that quinine hydrochloride (QHCl) produces a substantial suppression (> 40%) of the responses of PbN cells to sucrose. Sucrose stimulation has a reciprocal suppressive effect on the response to QHCl. These results imply that aversive and appetitive stimuli produce mutual inhibition in the gustatory system; studies of the chorda tympani nerve response suggest that this inhibition likely arises within the brainstem. A second line of investigation, using both an in vitro brainstem slice preparation and in vivo pharmacological manipulations of cells in the hamster NST, has demonstrated an inhibitory network within the rostral NST that plays a role in the modulation of taste activity. Patch-clamp and extracellular recording studies in vitro show that cells within the rostral central subdivision of the NST are inhibited by gamma-aminobutyric acid (GABA); this mediation is largely through the GABAA receptor subtype. Here we show that responses to taste stimulation recorded extracellularly from NST cells in vivo can be inhibited by local microinjections of GABA; this inhibition is blocked by the GABAA receptor antagonist bicuculline methiodide. Responses to sucrose are significantly more inhibited than those to NaCl or KCl. These combined lines of evidence show that appetitive and aversive stimuli activate mutually inhibitory systems within the brainstem and suggest that the basis for this interaction is a GABAergic inhibitory network within the NST.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878091 TI - Representation of hedonics and quality of taste stimuli in the parabrachial nucleus of the rat. AB - The distribution of evoked expression of the proto-oncogene c-fos was immunohistochemically examined in the parabrachial nucleus (PBN) of water deprived rats after free ingestion of palatable liquids, after intra-oral infusion of aversive taste solutions including various bitter substances, and after an intraperitoneal injection of LiCl. C-fos immunoreactive neurons (c-fos neurons) were densely packed in the external lateral subnucleus (els), external medial subnucleus (ems), dorsal lateral subnucleus (dls), central lateral subnucleus (cls), and the central medial subnucleus (cms) depending on the kind of stimulation. The rostral part of the els may be related to general visceral inputs; the caudal part of the els, negative hedonics or aversive behavior; the dls, positive hedonics or ingestive behaviour. Both the ems and the els may be related to taste information for bitter tasting compounds and HCl; the cls, for sucrose and saccharin; and the cms, for NaCl. PMID- 7878092 TI - Structural basis for bitterness based on Rabdosia diterpenes. AB - Bitterness of naturally occurring substances seems to be due to a balance between the "bitter unit" and the hydrophobic portions of the molecule. The study based on the Rabdosia diterpenes indicates that the bitter unit consists of a proton donor DH group and a proton acceptor A group. In addition to this DH-A unit, an A A unit may also be possible. The bitter compounds could enter the molecular structure of the receptor site with the bitter unit oriented into the aqueous phase by hydrogen bonding and the hydrophobic portion aligned into the lipid phase by dispersion forces. PMID- 7878094 TI - Is the bitter rejection response always adaptive? AB - The bitter rejection response consists of a suite of withdrawal reflexes and negative affective responses. It is generally assumed to have evolved as a way to facilitate avoidance of foods that are poisonous because they usually taste bitter to humans. Using previously published studies, the present paper examines the relationship between bitterness and toxicity in mammals, and then assesses the ecological costs and benefits of the bitter rejection response in carnivorous, omnivorous, and herbivorous (grazing and browsing) mammals. If the bitter rejection response accurately predicts the potential toxicity of foods, then one would expect the threshold for the response to be lower for highly toxic compounds than for nontoxic compounds. The data revealed no such relationship. Bitter taste thresholds varied independently of toxicity thresholds, indicating that the bitter rejection response is just as likely to be elicited by a harmless bitter food as it is by a harmful one. Thus, it is not necessarily in an animal's best interest to have an extremely high or low bitter threshold. Based on this observation, it was hypothesized that the adaptiveness of the bitter rejection response depends upon the relative occurrence of bitter and potentially toxic compounds in an animal's diet. Animals with a relatively high occurrence of bitter and potentially toxic compounds in their diet (e.g., browsing herbivores) were predicted to have evolved a high bitter taste threshold and tolerance to dietary poisons. Such an adaptation would be necessary because a browser cannot "afford" to reject all foods that are bitter and potentially toxic without unduly restricting its dietary options. At the other extreme, animals that rarely encounter bitter and potentially toxic compounds in their diet (e.g., carnivores) were predicted to have evolved a low bitter threshold. Carnivores could "afford" to utilize such a stringent rejection mechanism because foods containing bitter and potentially toxic compounds constitute a small portion of their diet. Since the low bitter threshold would reduce substantially the risk of ingesting anything poisonous, carnivores were also expected to have a relatively low tolerance to dietary poisons. This hypothesis was supported by a comparison involving 30 mammal species, in which a suggestive relationship was found between quinine hydrochloride sensitivity and trophic group, with carnivores > omnivores > grazers > browsers. Further support for the hypothesis was provided by a comparison across browsers and grazers in terms of the production of tannin binding salivary proteins, which probably represent an adaptation for reducing the bitterness and astringency of tannins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7878093 TI - Use of Vernonia amygdalina by wild chimpanzee: possible roles of its bitter and related constituents. AB - Bitter principles and related constituents have been isolated from Vernonia amygdalina (Compositae), a plant ingested by wild chimpanzees sometimes suffering from parasite-related diseases in the Mahale Mountains National Park, Tanzania. These isolated constituents were the known sesquiterpene lactones (vernodalin, vernolide, hydroxyvernolide), and new stigmastane-type steroid glucosides (vernonioside A1-A4: for bitter tasting constituents and vernonioside B1-B3; for nonbitter related constituents). Antiparasitic activity tests of these constituents together with quantitative analyses of the major active constituents, vernodalin and vernonioside B1, supported the hypothesis that Mahale chimpanzees control parasite-related diseases by ingesting the pith of this plant, found to contain several steroid-related constituents. While the major active steroid-related constituents (vernonioside B1 and its primary aglycone, vernoniol B1) do not taste bitter themselves, it was hypothesized that the highly bitter constituents including vernodalin may play an important role as signals to the ingester guiding their choice of the appropriate plant, plant part, and possibly also as signals which help to control the amount of intake. PMID- 7878095 TI - Influences on acceptance of bitter foods and beverages. AB - Bitterness is generally viewed as an undesirable attribute of foods and beverages, yet segments of the population regularly ingest items with a prominent bitter taste. The influence of taste sensitivity, exposure, selected personality traits (i.e., neophobia, variety seeking, sensation seeking) and pharmacological reactivity on alcohol and caffeine consumption, two widely consumed bitter substances, was assessed in 20 healthy adults (10 male, 10 female). Self-reported alcohol use was positively correlated with measured ethanol taste detection threshold and pharmacological reactivity (self-reported behavioral effects). The latter accounted for 23% of the variance in alcohol intake. Caffeine intake was significantly associated with personality traits. Sensation seeking status and self-reported reactivity to caffeine accounted for 46% of the variance in caffeine intake. Pleasantness ratings for novel bitter and sour foods were unaffected by 10 exposures whereas increased ratings were given to sweet and salty items. Variation in the influence of these factors between individuals and across products may explain individual differences in the acceptability and use of foods and beverages containing alcohol, caffeine and other bitter compounds. PMID- 7878097 TI - Perceptual interactions in mixtures containing bitter tasting substances. AB - Mixtures of Quinine HCl and NaCl elicit heterogeneous taste percepts. Each such percept consists of a bitter and a salt sensation. Using functional measurement in combination with a two-stimulus procedures, it was found that the NaCl suppresses the QHCl bitterness and that QHCl has almost no suppressive effect on NaCl saltiness. In addition, it was shown that the total intensity of the mixture percept is almost identical to the sum of the intensities of the bitterness and saltiness sensations-within-the-percept. As was found in earlier experiments with mixtures of other tastants, central sensory integration within a heterogeneous percept seems to be a fairly simple additive process. PMID- 7878096 TI - Bitter taste in aging: compound-specific decline in sensitivity. AB - Threshold sensitivity to and the perceived intensity of two bitter compounds, quinine sulfate and urea, were assessed in 52 young adults and 60 elderly adults. Consistent with previous literature, age-related declines in sensitivity to the bitterness of quinine were observed at both threshold and suprathreshold levels. In contrast, the same young and elderly subjects showed comparable sensitivity to the bitterness of urea. These results provide further support for the existence of multiple bitter taste transduction sequences in humans, and indicate that they may be differentially affected by aging. PMID- 7878098 TI - Bitterness in wine. AB - Bitterness in wine is elicited primarily by flavonoid phenols, which are bitter and astringent, and by ethanol. Monomeric flavonoid phenols are primarily bitter but as the molecular weight increases upon polymerization, astringency increases more rapidly than bitterness. The chiral difference between the two wine flavan-3 ol monomers produces a significant difference in temporal perception of bitterness: (-)-epicatechin is significantly more bitter and had significantly longer duration of bitterness than (+)-catechin. Ethanol enhances bitterness intensity and duration, whereas varying wine pH has little or no effect on perceived bitterness. Whereas PROP status had no significant effect on temporal perception of bitterness or astringency, subjects with low salivary flow rates took longer to reach maximum bitterness and astringency intensity and reported longer persistence of both attributes than high-flow subjects. PMID- 7878099 TI - Chemoreception and perception of the bitterness of isohumulones. AB - Psychophysical experiments were conducted to determine whether isohumulones share a common receptor mechanism with other bitter compounds, and whether parotid saliva flow affects perception of their bitterness. Findings from a study of inter-individual differences in sensitivity to 23 sweet and/or bitter compounds among 25 subjects using the time-intensity (TI) method suggest that isohumulone and tetrahydroisohumulone may share a common receptor mechanism with other bitter compounds except those with the thiourea moiety. Isohumulone and tetrahydroisohumulone displayed a unique dome-shaped TI profile. The bitterness of the two compounds took longer to develop, but it lasted as long as for other bitter stimuli. In a study of the relation between perception of bitterness in beer and parotid saliva flow in 20 young adults, no significant difference was found among the mean saliva flows triggered by 0, 15 and 30 mg/L of isohumulones added to beer, and no significant correlation was found between saliva flow and maximum intensity or total duration of bitterness. PMID- 7878100 TI - Maximal exercise and acute mood response in women. AB - The present study was designed to characterize and assess the reliability of acute mood responses to maximal exercise in women. All subjects (N = 22; age = 45 +/- 2.5 yr; BMI = 24.3 +/- 0.9 kg/m2) participated in two maximal walking tests spaced approximately one month apart. The abbreviated Profile of Mood States (POMS) questionnaire was administered immediately prior to and within 5 min following maximal exercise at both occasions. Maximal heart rate, rating of perceived exertion, and functional aerobic capacity responses indicated compliance to maximal exertion at both tests. Using repeated measures ANOVA, no significant (p < .05) differences were noted between the two tests for any of the POMS subscales. Significant pre to postexercise increases were noted for fatigue and self-esteem subscales while the tension and vigor affects significantly decreased. Because no interactions were found, these effects are concluded to be independent of the order in which the tests were performed. Additionally, intraclass correlations computed for each respective POMS subscale, ranged between 0.69 and 0.81 for fatigue, tension, vigor, self-esteem, confusion, and total mood disturbance. The anger and depression subscales were noted to have intraclass correlations of 0.29 and 0.43, respectively, and may have been influenced by a floor effect in this study population. It is concluded that the abbreviated POMS questionnaire may be reliably used to assess acute mood responses to maximal exercise in women and that even maximal exertion has the potential to acutely benefit mood by decreasing tension and increasing self esteem. PMID- 7878101 TI - Symmetrical generalization between the discriminative stimulus effects of gamma hydroxybutyric acid and ethanol: occurrence within narrow dose ranges. AB - Gamma-hydroxybutyric acid (GHB) has been shown to reduce ethanol consumption and suppress ethanol withdrawal syndrome both in laboratory animals and humans. The present study was designed to assess the similarity between the discriminative stimulus effects, or subjective feelings, of GHB and ethanol using a T-maze, food reinforced drug discrimination procedure. Three groups of rats were trained to discriminate ethanol (1.0 or 2.0 g/kg; p.o.) or GHB (300 mg/kg; p.o.) from water. In the 1.0 g/kg ethanol-trained rats, substitution for ethanol was an inverted U shape function of GHB dose, with only 300 mg/kg GHB resulting in complete substitution for ethanol. No dose of GHB elicited selection of ethanol appropriate arm higher than 10% in the 2.0 g/kg ethanol-trained group. In the 300 mg/kg GHB-trained rats, complete substitution for GHB occurred only at the dose of 1.0 g/kg ethanol. Doses of ethanol lower or higher than 1.0 g/kg did not substitute for GHB. The results of the present study indicate that symmetrical generalization between ethanol and GHB occurred within narrow dose ranges. They are discussed in terms of common neurotransmitter systems involved in the mediation of GHB and ethanol effects. PMID- 7878102 TI - Effects of ethanol, caffeine, and clorazepate on hypertonic NaCl solution intake in rats. AB - Previous reports indicate that several anxiolytics enhance the intake of hypertonic saline in rehydrating rats. This experiment was conducted to determine the effects of repeated (5 sessions) injection (i.p.) of ethanol (0.4 or 0.8 g/kg), caffeine (20 or 40 mg/kg) or clorazepate (3 mg/kg) on the ingestion of hypertonic saline (1.8%) in water-deprived rats. Saline intake increased with the acute administration of both clorazepate and ethanol (two doses), but it decreased with caffeine (two doses). It seems that the increase or decrease of hypertonic saline ingestion following acute drug administration continues to correlate well with anxiolytic or anxiogenic actions. However, following repeated administration of caffeine and ethanol, the effects on saline intake were not maintained in a reliable manner. PMID- 7878103 TI - Ontogeny of thermoregulation in the Djungarian hamster (Phodopus campbelli). AB - At birth, altricial Djungarian hamster pups require exogenous heat to grow and gain little benefit from huddling with their littermates. By day 6 huddled pups begin effective thermogenesis although isolated pups do not show spontaneous increases in temperature until day 9. On day 12, isolated pups can resist cooling for short periods of time and huddles do not cool within a 15 min test. By day 15, isolated pups can thermoregulate, although at a lower core body temperature than is typical of adults, and both huddling contact with littermates and direct contact with the dam are reduced. At weaning, pups are effectively thermally independent. This ontogeny is correlated with behavioral, morphological and physiological changes during pup development including brown adipose tissue (BAT) thermogenesis, pelage development and body size. The onset of thermogenesis, and then thermoregulation, causes temporary reductions in pup growth rate on days 6 and 7 and again on days 12 and 13. Body weight, rather than pup age, appears critical for independent thermoregulation. These results are discussed relative to the extent of maternal hyperthermia and the physiological demands of the concurrent gestation characteristic of reproduction in Djungarian hamsters. PMID- 7878106 TI - Juvenile circadian core temperature rhythm in Wistar and lean (Fa/-) Zucker rat pups. AB - We compared the daily rhythms of cold defense in Wistar and lean (Fa/-) Zucker rat pups isolated from maternal care. Pups, born in a colony with lights-on from 7:00 to 19:00, were artificially reared from 10 to 13 days of age in continuous light at moderate cold loads, while we recorded core temperature (Tc) and metabolic rate (MR). Pups of both strains showed daily rhythms distinctly different from those of adult rats: on the first day of artificial rearing Tc steeply decreased shortly before the time of lights-on in the breeding colony and reached a daily minimum of 31.8 +/- 0.4 degree C at 7:17 +/- 17 min in Zucker pups (+/- SE, N = 24) and of 33.4 +/- 0.2 degree C at 8:59 +/- 9 min (N = 25) in Wistar pups. On each day, the average daily minimum Tc was significantly higher in Wistar than in Zucker rats, whereas the daily maximum Tc were close to 36 degrees C in both strains. The daily rhythms of MR resembled those of Tc. We conclude that circadian differences of cold defense, which must be expected to influence a variety of behavioral and physiological parameters, are not a peculiarity of Zucker rat pups but also occur, though with a smaller amplitude, in 10-day-old Wistar pups. PMID- 7878105 TI - A contact eatometer for automated continuous recording of feeding behavior in rats. AB - A new contact eatometer designed and built in our laboratory is described. The system makes possible the reliable continuous recording of feeding behavior in rats from the time of weaning, without significantly affecting food intake- and growth-related variables. Improved time discrimination and reliability of records -along with the small financial outlay necessary to manufacture the device--make the system appropriate for chronobiological studies which involve the simultaneous use of a large number of animals. PMID- 7878104 TI - Ingestive response shows absence of taste aversion after bovine satietin in rats. AB - Six adult male rats (409 +/- 16 g) were equipped with chronically implanted oral catheters. Facial consummatory responses to gustatory stimuli, of 50 microliters 2.0 mol.1-1 banana or coconut flavoring, were recorded on a +4/-4 scale for 30 s. The new flavors were paired with IP injections on three different days. The rats were injected with either saline or 1 mg.kg-1 bovine serum satietin (bs-SAT). Food intake and body weight were reduced (p < 0.005) after satietin but not after saline. Both coconut and banana flavors aroused mild ingestive responses in the naive rats. Five days after the beginning of the pairing with IP injections, the rats' response to coconut and banana remained unchanged. The results show that satietin was able to reduce food intake and body weight but did not arouse taste aversion. PMID- 7878107 TI - Norepinephrine inhibition of water and food intake: comparison with vasopressin effects. AB - In a previous publication we showed that intraperitoneally (IP) injected norepinephrine (NE) induces hypodipsia (hD) in rats by an alpha 1-adrenergic effect which might be due to splanchnic vasoconstriction. In the present work we administered two vasoconstrictive hormones: NE 250 ug/kg and arginine vasopressin (VP) 550 mU/kg either by IP or intramuscular (IM) route to fasted rats in two different thirst-inducing conditions: (a) water-deprivation; or (b) induced hyperosmolarity. IP NE inhibited significantly food and water intake under both conditions. IM NE did not affect food intake and elicited significantly less hD and this only in (a). VP did not affect food intake but induced hD regardless of the route of administration in (a) but not in (b). NE administrated to anesthetized rats after food and water deprivation increased arterial pressure by both routes while VP effect was weaker and more variable. IN CONCLUSION: blood pressure elevation may be implicated in the hD effect but IP NE elicits a specific splanchnic action; splanchnic-induced hypophagia is not necessarily related to water intake inhibition. PMID- 7878108 TI - Exercise in food-restricted rats produces 2DG feeding and metabolic abnormalities similar to anorexia nervosa. AB - Anorexia nervosa (AN) is associated with a paradoxical reduction in hunger ratings following 2-deoxy-D-glucose (2DG) induced glucose insufficiency. Because of the relationship between exercise and AN, there is interest in the weight-loss phenomenon produced by exercise in food restricted rats. This investigation determined if the weight-loss phenomenon is associated with a paradoxical suppression of food intake following 2DG and if the effect is related to reductions in prevailing glucose and insulin levels. Weight-matched, normal weight exercised and normal-weight unexercised rats served as controls. As predicted, 2DG reduced food intake in animals subjected to the phenomenon (1.5 h/day food access and 22.5 h/day running wheel access). This effect was related to reductions in plasma glucose and insulin under the conditions that prevailed at the time of injection. Since these changes also occurred in weight-matched controls, they were attributed to the general effects of weight loss. A situational specificity for the "anorexia" of the weight-loss syndrome was also demonstrated. Finally, the strengths and weaknesses of the phenomenon as a model of AN were considered. PMID- 7878109 TI - Dopamine D1 and D2 effects on fetal mouthing responses to milk. AB - Rat fetuses exhibit prompt responses to an intraoral infusion of milk, including mouthing movements and an increase in motor activity. Two experiments examined the involvement of dopamine D1 and D2 receptors in mediating these fetal responses to milk. The D1 agonist SKF-38393 and the D2 antagonist sulpiride diminished fetal mouthing responses. Mouthing responses appeared normal in fetuses treated with the D2 agonist quinpirole or the D1 antagonist SCH-23390. These findings suggest that activity in the dopamine system may inhibit mouthing within 30 s of milk infusion. PMID- 7878111 TI - Destruction of neurons in the VPM thalamus prevents rabbit heart rate conditioning. AB - The present study examined the role of the ventral posterior medial nucleus of the thalamus (VPM) in classical heart rate (HR) conditioning using an acoustic conditioned stimulus (CS) and a corneal air puff unconditioned stimulus (US). Previous research suggests that VPM neurons are activated during the presentation of a corneal air puff US. Rabbits were given ibotenic acid lesions in the VPM and subjected to one Pavlovian HR conditioning session. The results of the present study demonstrate that destruction of cell bodies in the VPM reduces HR conditioning to the level of a pseudoconditioning control without affecting HR baseline, or orienting responses to the CS. Lesions of the VPM also significantly augment the tachycardiac unconditioned response, suggesting that VPM lesions alter the somatosensory processing of the US. PMID- 7878110 TI - Estradiol interacts with gastric or postgastric food stimuli to decrease sucrose ingestion in ovariectomized rats. AB - The sham feeding preparation was used to determine whether systemic estradiol administration inhibits the intake of 0.8 M sucrose of ovariectomized rats by decreasing the potency of pregastric controls of ingestion. During real feeding, significant reductions in the sucrose intake of estradiol-treated rats appeared within 5-6 min. In contrast, estradiol had no effect on sham feeding at any time. The lack of effect of estradiol on sham feeding indicates that pregastric stimuli are not sufficient to mediate the inhibitory effect of estradiol on feeding in ovariectomized rats. Rather, because estradiol did inhibit real feeding, gastric and/or postgastric food stimuli are necessary for this inhibitory effect. The rapid onset of estradiol's inhibitory effect on real feeding suggests that these postingestive stimuli are selective for controls of the initial phase of the meal. PMID- 7878112 TI - Effects of chronic mild stress on serum complement activity, saccharin preference, and corticosterone levels in Flinders lines of rats. AB - Complement proteins and fragments participate in the induction and modulation of specific and nonspecific immune reactions. We have examined the effect of 4 weeks of chronic mild stress (CMS) on complement sheep red blood cell hemolytic activity measured in CH50 units in two selectively bred lines of rats, the Flinders resistant line (FRL) and the Flinders sensitive line (FSL), that differ in cholinergic sensitivity and behavioral characteristics. Additionally, CMS induced hedonic deficit (decreased preference for 0.02% saccharin over water) and serum corticosterone levels were compared in FRL and FSL rats. CMS caused a significantly (p < 0.01) greater decline in CH50 responses in FSL (-15%) than in FRL (-7%) rats. This was accompanied by a significant (p < 0.01) suppression of saccharin preference over a 24 h period in both FRL and FSL rats. Both lines showed a similar, more than 2-fold (p < 0.01) increase in corticosterone levels following CMS. These results further confirm that CMS induces a depressive-like state in rats as well as the validity of the FSL rat as a genetic model of depression. They also indicate that the effect of stress on the immune system can be monitored by measuring the complement CH50 response. PMID- 7878113 TI - Medial preoptic alpha-2 adrenoceptors in the regulation of sleep-wakefulness. AB - Adrenergic alpha 2 agonist (clonidine) and its antagonist (yohimbine) were locally applied to the medial preoptic area (mPOA), to find out the role of alpha 2 receptors at this brain region in the regulation of sleep-wakefulness. Clonidine produced arousal, whereas yohimbine induced sleep in freely moving animals. Behavioural arousal produced by clonidine administration was accompanied by EEG synchronization. The alpha 2 receptor as the probable site of action of externally applied norepinephrine (NE), is discussed. PMID- 7878114 TI - Effect of delta 9-tetrahydrocannabinol on short-term memory in the rat. AB - We have reported that marihuana and its principal psycoactive compound, delta 9 tetrahydrocannabinol (delta 9-THC) produce alterations in several cerebral areas after acute treatment. Based on the involvement of 5-hydroxytryptamine (5-HT) on memory and learning and the reported effects of delta 9-THC on short-term memory, we designed an experiment to evaluate the memory performance and its possible relationship with serotonergic alterations after delta 9-THC administration. Male Wistar rats received an acute oral dose of THC (5 mg/kg). Short-Term memory was tested on a radial 8-arm maze with a 5 s delay, after 35 days of training. The animals were food deprived and adjusted for growth. 5-HT and its metabolite, 5 HIAA, levels were measured in cerebral cortex, dorsal hippocampus, ventral hippocampus, rostral neoestriatum and amygdala basal nucleus, by HPLC-ED. The experiment indicates an impairment of short-term memory in the radial maze test after delta 9-THC administration. The control group performed the test without errors, while the treated group made a significant number of errors (Z = 0.019, Mann-Whitney test). This behavioral effect did not seem to be related to serotonergic alterations, as the 5-HT turnover rate was not different between treated and control animals. PMID- 7878115 TI - Odor-induced inhibition of intake after pairing of odor and CCK-8 in neonatal rats. AB - This study determined whether an odor that was paired with injections of CCK octapeptide would later come to inhibit independent feeding in neonatal rats. An odor so paired in rats that were not food or maternally deprived later reduced feeding during the infants' first independent feeding experience. Devazepide, the CCKA receptor antagonist, blocked the reduced intake when injected prior to the feeding test. These studies demonstrate that CCK is an effective unconditioned stimulus even when the animal is not eating during the conditioning process. Furthermore, the conditioned stimulus (the odor) causes behavioral change either by sensitizing a system that includes the CCKA receptor, by causing the release of endogenous CCK, or by changing some non-CCK system that enhances the processing of CCKA receptor-mediated information. PMID- 7878116 TI - Sexual play behavior in lambs androgenized in utero. AB - In lambs, play behavior, mainly including male-like sexual behavior patterns, is observed during weeks 4-8 following birth. The higher frequency of this behavior in male lambs has no obvious relationships with secretions of testosterone during infancy. In our experiment, pregnant ewes received subcutaneous implants of testosterone on gestation day 50. The frequency of male-like sexual patterns did not differ reliably between female lambs born to treated ewes and male lambs born to treated or control ewes. However, the frequency was lower for female control lambs. These results suggest that sexually dimorphic social play in lambs is dependent on prenatal exposure, which seems to have a masculinized effect. PMID- 7878117 TI - Attenuating effect of arecoline and physostigmine on an impairment of mealtime associated activity rhythm in old rats. AB - In the present study, we examined whether cholinergic drugs such as arecoline and physostigmine attenuated an impairment of time perception presented by daily scheduled feeding in aged rats. When feeding was restricted to a single meal at a fixed time of day (13:00-17:00) for 6 successive days, young rats exhibited intense locomotor activity from 1-3 h before feeding time. Intense locomotor activity was observed between 12:00-17:00 in young animals even on the fasting day (on day 7) (mealtime-associated activity). However, this mealtime-associated activity was impaired in old rats. Daily injection of arecoline (10 mg/kg) or physostigmine (0.1 and 0.2 mg/kg) at 17:00 for 6 successive days attenuated the impairment of mealtime-associated activity on the fasting day in a dose-dependent manner in old rats, whereas daily treatment with D-glucose (100 or 2000 mg/kg) did not. The results of the present study suggest that cholinergic drugs attenuate the impairment of the manifestation of mealtime-associated anticipatory activity related to 'temporal learning' in old rats. PMID- 7878118 TI - Does a history of convulsions increase the amnestic effect of temporal region brain lesions? AB - Rats with surgical lesions of the hippocampal formation, amygdala, and nearby neocortex and pyriform cortex were impaired on a swim-to-platform test and on a passive avoidance test. These impairments were not increased by presurgical treatment with a series of 21 electroshock convulsions. To the extent that this rat preparation can be compared with human patients, the data suggest that a previous history of epileptic seizures does not increase the amnestic effect of temporal lobe lesions. PMID- 7878119 TI - Telemetered temperature monitoring in preweanling Mongolian gerbils (Meriones unguiculatus). AB - Like most small mammals, Mongolian gerbils (Meriones unguiculatus) are born without the ability to maintain core body temperature (Tb). Breeding adults, juvenile alloparents, nest materials, and other litter mates probably contribute to the maintenance of core body temperature in neonates, but the relative role of each factor is unknown. We developed a procedure allowing biotransmitters to be implanted into 9-day-old pups for use with a radiotelemetry system. Experiment 1 demonstrated the development of thermoregulatory capacity over postpartum days 11, 15, and 19. Pups at 11 days of age lacked thermoregulatory capacity, and maintained Tb only slightly above the ambient temperature (15 degrees C) of the testing environment. The transition from poikilothermy to homeothermy was clearly accomplished by day 19, with pups maintaining Tb of 35.8 +/- 0.2 degrees C for at least 100 min. Experiment 2 measured Tb in 11- and 12-day-old pups during a thermal challenge (15 degrees C) in the presence of nest materials, litter mates, or both. Pups provided with either nest materials, litter mates, or both maintained higher Tb during a 40-min test than those without these resources. Our methodology minimizes disruptions and the thermal consequences associated with other invasive (rectal probe thermistors) and noninvasive (e.g., infrared thermography) procedures. PMID- 7878120 TI - Feeding patterns of rats when food-access cost is alternately low and high. AB - Rats living in a laboratory foraging paradigm began each meal by bar pressing to procure access to food and then could eat any amount. In different conditions the procurement price changed from low (10 bar presses) to high (200 or 400 bar presses) every ten days, five days, or one day, or on schedules of one-day low/two-days-high, or one-day-low/four-days-high. In a final condition, the price alternated at every meal. Meals were less frequent and larger on high-price days. In the ten- and five-day alternations, the rats adjusted meal frequency on the first day of a price, but changed meal size gradually over the first few days; by the fifth day, daily intake was not different on low- and high-price days. In the one-day alternations, the rats ate less food, and in some cases did not eat at all, on high-price days, and lost weight. Intake was greater than normal, and body weight recovered, on low-price days. This pattern saved foraging cost at the expense of greater-than-normal daily fluctuations in food intake and body weight. When two or four days of high price alternated with one day of low price, the rats did eat on the first day of high price, suggesting they may integrate costs over a time window greater than 24 h. PMID- 7878121 TI - Pleasure and excess: liking for and overconsumption of chocolate. AB - Responses to three different presentations of a highly liked food (chocolate) were measured in two groups of female subjects. One group of subjects identified themselves as overeaters of chocolate (overeaters), while the other group of subjects were of a similar age and body mass index, but ate this food in moderation (controls). The three conditions of presentation were (a) a fixed amount of milk chocolate; (b) ad lib access to milk chocolate; and (c) a self selected amount of the individual's most preferred form of chocolate. The main findings were that variables associated with the excitation of appetite (hunger, desire to eat, prospective consumption) were higher in overeaters and variables associated with the inhibition of appetite (fullness, changes in pleasantness and pleasure of eating) were lower in overeaters relative to controls. It is suggested that investigations of individuals who eat certain foods to excess can inform our understanding of normative and aberrant eating behaviour. PMID- 7878122 TI - Compound structure of rodents activity rhythm. AB - In the present study an attempt to determine the fine structure of rodents activity rhythm was carried out. To eliminate masking effects which are produced by the active influence of the monitoring system on the behavior of the animal (e.g., running wheel) we designed a passive infra red detection system. Rats were exposed to light-dark 12:12 [LD(12:12)] cycles and mice to LD(12:12), LD(8:16) and LD(16:8) cycles. Multiwave patterns of activity were observed in both rodents genera which differ from each other in the number of activity bouts and the periods of the activity rhythm components. In LD(12:12), rats exhibited 2 bouts of activity and 1 bout of rest which were attributed to the presence of 24 and 8 h components. Mice, exposed to the three varying ratios of L to D regimens exhibited 3 bouts of activity and one bout of rest which were attributed to the presence of 24 and 6 h components. The relation of the compound structure to the 24 h rhythm is discussed. PMID- 7878123 TI - Alteration in circadian rhythm of plasma corticosterone in rats following sociopsychological stress induced by communication box. AB - The purpose of present study was to investigate the physiological characteristics of sociopsychological stress induced by the communication box method. In this method, the nonfoot shocked rats were used as the psychological stressed experimental group. The stress exposure was loaded for 1 h between 0900 and 1000, daily. The changes in circadian rhythm of plasma corticosterone were studied following the 3-day, 5-day, or 10-day stress exposure, respectively. Plasma corticosterone levels of foot shocked rats and nonfoot shocked rats following the 3-day or 5-day stress exposure were significantly higher than those of control rats. Particularly, the marked elevation of plasma corticosterone was observed at the peak time of circadian rhythm (2100) in the both stress groups. Consequently, the amplitude of 24 h rhythm increased significantly, but the acrophase was not changed. However, the changes of plasma corticosterone levels of both stress groups following the 10-day stress exposure approached those of control group. These results suggest that the repeated exposure of sociopsychological stress can influence the circadian rhythm of plasma corticosterone. The communication box method may be a valuable tool for researching the etiology of human psychiatric disorders with rhythm disturbance. PMID- 7878124 TI - Water deprivation, plasma osmolality, blood volume, and thirst in young pigs. AB - When deprived of both drinking water and food, pigs failed to develop the hyperosmolality usually expected with dehydration. In further studies 12 pigs were deprived of drinking water and food, and the effects were compared with data from nondeprived pigs, pigs water deprived but with food available, and pigs with water but no food. When food was eaten during water deprivation, plasma osmolality rose to levels sufficient to stimulate drinking. During water and food deprivation, plasma osmolality failed to rise, even over 24 h, and usually fell. Blood volume changes were calculated from packed cell volume and plasma protein data, and it was found that blood volume fell significantly when both food and water were withheld, but not when only water was withheld. It appears that the conditions of deprivation determine the proportions of thirst stimulation that can be attributed to plasma hypertonicity and to hypovolemia. PMID- 7878125 TI - Estrus-associated decrements in a water maze task are limited to acquisition. AB - To ascertain whether gonadal hormones have activational influences on spatial ability, the relationship between estrous cycle, sex differences and water maze performance was examined in two studies. In the first study, the performance of females at different cycle phases was compared within females and to that of males. All animals were naive to the task. Similar to other studies, females had longer latencies and distances to reach the water maze platform than males. This sex difference was statistically significant only in comparisons of estrous females and males, not in comparisons of diestrous females and males. To determine whether estrus-associated decrements in acquisition of the water maze task extended to postacquisition performance, a second study assesessed performance of ovariectomized rats--trained to criterion in the task--whose cycle phases were mimicked by exogenous hormones. In the initial trial, "estrous" animals had longer latencies to reach the platform than "diestrous" and ovariectomized animals. In subsequent trials, no hormone-dependent differences in performance were observed. Taken together, the results indicate a modest association between phase of estrous cycle, acquisition, and postacquisition performance when the task is novel. These findings suggest estrus-associated decrements in acquisition may account for previous discrepancies among studies of sex differences in spatial ability. PMID- 7878126 TI - Perseveration without hyperlocomotion in a spontaneous alternation task in rats sensitized to the dopamine agonist quinpirole. AB - Behavioral sensitization induced by intermittent injections of the dopamine agonist quinpirole is characterized by hyperlocomotion and perseveration. This study tested whether in sensitized rats, the expression of perserverative behavior can be independent of hyperlocomotion. Rats received 10 injections of either quinpirole (0.5 mg/kg) or saline in a T-maze apparatus, a procedure that induced locomotor sensitization in the drugged animals. When tested later (under quinpirole) for spontaneous alternation in the same T-maze, in a discrete trial procedure, sensitized rats showed decreased spontaneous alternation, compared either to saline controls or acute quinpirole. The decrease in spontaneous alternation showed a tendency to be lower than chance level of alternation, suggesting perseveration. The possibility is discussed that the sensitization reduced spontaneous alternation may relate to a diminution in the sense of task completion, and the increased perseveration may model a form of compulsive "checking" shown in obsessive-compulsive disorder. PMID- 7878127 TI - Functional association between the medial amygdala and the medial preoptic area in regulation of mating behavior in the male rat. AB - We examined the effects of combined lesions of the medial preoptic area and the medial amygdala on male copulatory behavior to understand a functional relation between these two structures in regulation of the behavior in the rat. Young adult male rats were castrated and received Silastic implants containing testosterone. After baseline copulatory tests, a unilateral medial preoptic lesion (uPOL) was made. Males with uPOL showed less intromission behavior than sham-operated males did, but none of them showed elimination of the behavior. Following the observations after the uPOL, these males were subjected to a unilateral medial amygdala lesion (uMAL) ipsilateral or contralateral to the previous uPOL. The ipsilateral uMAL did not affect copulatory behavior compared to that of sham-operated uPOL males. However, the copulatory behavior in the animals with uPOL was severely disrupted by the contralateral uMAL. These results suggest that the medial preoptic area is closely related to the medial amygdala in regulation of male rat copulatory behavior, and these areas may play a critical role in the behavior as an unitary system. PMID- 7878128 TI - Agonistic profile and metabolism in alevins of the Nile tilapia. AB - Metabolic differences derived from social stress usually show data with high variance that may hinder the finding of important differences. Since such high variance may be caused by agonistic variability occurring during social interactions, this work tested whether metabolism is associated with agonistic profile in the cichlid fish Nile tilapia, Oreochromis niloticus (L.). Metabolism was inferred from oxygen consumption, resistance to progressive hypoxia and ventilatory rate. Fifteen pairs of alevins were used for each metabolic and behavioral series. An ethogram based on 8 types of agonistic interactions was employed. Agonistic profiles were determined and associated with the physiological parameters later on. The test of canonical correlation showed significant association between some agonistic profiles and metabolism. Ventral nipping and lateral fight appeared as the two most important in promoting association with metabolism. PMID- 7878129 TI - Three-factor eating questionnaire and the use and liking of sweet and fat among dieters. AB - The aim of this study was to examine whether the cognitive restraint, disinhibition and hunger factors of the three-factor eating questionnaire (TFEQ) can differentiate between low and high use, desired use and liking of various sugar- and fat-containing foods. A questionnaire with items on 44 foods and the TFEQ was obtained from 253 women taking part in weight reduction program. Principal component analysis was used to divide the foods into ten groups by their reported usage. The cognitive restraint factor was related to the reported use of some food groups such as fruit-based sweet foods, butter, margarine and regular-fat cheese, but not to the desired use or liking. High disinhibition and hunger scores were related to frequency of reported and desired use and to liking of several food groups (e.g., sweets, pastries served with coffee, fruit-based sweet foods, butter and margarine). Those scoring highest on cognitive restraint and lowest on disinhibition and hunger reported using all food groups less frequently than those with the lowest scores on restraint and the highest scores on disinhibition and hunger, except low-fat cheese and yogurt. These groups also differed in the desired use and liking of most sweet foods. PMID- 7878130 TI - Taste performance in Sjogren's syndrome. AB - Sjogren's Syndrome (SS) patients have impaired salivary gland function and an elevated frequency of oral complaints. The taste complaints are thought to be due to sensory deficits that arise in the absence of sufficient saliva to maintain taste receptors. We assessed the subjective complaints, salivary production and taste functioning of SS patients and unaffected individuals. We found the expected decreased salivary gland function and increased frequency of taste complaints. Our taste assessment with weak stimuli confirmed and expanded the previous report of decreased taste threshold sensitivity in SS. However, perception of stronger taste stimuli was not impaired. In contrast with previous reports, patient judgments of intensity were not significantly reduced for any of the four taste qualities. Although the salivary gland function of all patients was markedly impaired relative to that of controls, patients lacking measurable salivary flow were no more likely than patients with residual function to exhibit subjective complaints or taste impairments. Our observations are inconsistent with a simple causal chain running from salivary gland dysfunction to sensory loss to taste complaints. PMID- 7878132 TI - [Ideal of psychiatric care and the development of the medical care delivery system in postwar Japan]. PMID- 7878131 TI - Involvement of the main but not the accessory olfactory system in maternal behavior of primiparous and multiparous ewes. AB - The respective roles of the main and accessory olfactory systems in the development of maternal behavior and selective suckling were investigated in parturient primiparous and multiparous ewes. Vomeronasal nerve section before parturition did not disturb either maternal behavior or maternal selectivity at suckling. By contrast, anosmia induced by zinc sulphate infusion had significant effects on the onset of maternal behavior in primiparous ewes. The onset of licking and of suckling were delayed and licking times and maternal bleats were reduced. Such disturbances were not observed in multiparous anosmic ewes, indicating that experience can compensate for the loss of olfactory information. On the other hand, anosmia prevented selective care regardless of maternal experience. Our results underline the importance of the main olfactory system for the development of adequate maternal behavior in sheep. PMID- 7878133 TI - [Relationship between psychopathology and biological psychiatry]. PMID- 7878134 TI - [The current status of informed consent in psychiatry]. PMID- 7878135 TI - [Incest: murder of the identity]. AB - The author begins by describing incest in the context of a change in attitude toward it and a substantial increase in forensic referral. This is followed by the description of the psychological profile of abusing fathers and how the traumatic experience severly shatters the sense of identity in the victims. Some clinical examples illustrate the role of negative hallucination, basic violence and the phenomenon of the double. The author also approaches the mental functioning of the abusers through the angle of perversion and attempts to define some necessary therapeutic conditions. PMID- 7878136 TI - [Brief analytic essay on unconscious forces facilitating transgenerational repetition of physical or sexual abuse]. AB - Transmission of abusive conduct is mainly determined by unconscious guilt and identification with the aggressor. The abused child is bound to split the parental object. The hostile side is eclipsed due to dependence and regression. Therefore deprived of the hated object, the guilt surges forcefully with the role reversal of the following generation. The former victim, whose identifications with the aggressor are actuated, discharges his guilt by projective identifications with the new victims. The ongoing splitting perpetuates the pathology of the relation. PMID- 7878137 TI - [Credibility of allegations of under age minors regarding sexual abuse]. AB - When a child under age states he/she has been sexually abused, there seldom exists an objective certainty to support the allegation. Whereas clinicians know that a child who speaks spontaneously probably speaks the truth, it is nonetheless difficult to exclude the possibility of fabulating, lying or mistaking. The error probability is sharply increased when abuse is referred by a parent, specially in a context of parental separation. This article thus presents a review of criteria which help to better assess the truth or error of allegations. Criteria include analysis of the child's talk, application of projective techniques, observation of his/her behavior, etc. The author also describes some differential diagnoses based on the behaviors and sexual allegations of children under age. PMID- 7878138 TI - [Nightmares--dreams and thought processes]. AB - After reviewing the literature concerned with the function of dreaming and especially dreaming in the child, the author presents various theories about the role of dream, with special emphasis on S. R. Palombo's theory on the relationships between dream and memory. The proposed hypothesis, which is based on various elements (as study of nightmares in children, oniric life of pregnant or post-partum women, occurrence of nightmares in autistic children and counter transferential drowsiness in the analyst) takes nightmares as a more or less complete failure of the primarization processes of primary significants. The issue of dreams and nightmares is being related here with the now classical distinction of psychic processes in originary, primary and secondary ones. To be sure, this is but a mere metapsychological hypothesis which needs to be developed by further clinical studies. PMID- 7878139 TI - [The Bertrand Cramer and Francisco Palacio-Espasa method of mother-infant psychotherapy]. PMID- 7878140 TI - [Epidemiologic approach to the evolution by age and sex of childhood and adolescent depression]. AB - Review of the literature on the epidemiology of depression in children and young adolescents taking into account the age and sex evolution of 1/its frequency, 2) its symptoms, 3) the risk factors and 4) prognostic factors, shows the following: age evolution of depressive conditions (self-perceived depression and clinical disturbances) is different according to sex and type of disturbances. In early adolescence there is an increase in frequency of depressive feelings, specially in girls. Clinical depression also differs according to sex: boys seem to present more severe depressions and at a younger age, more frequently associated with behavior problems and have a worse prognosis. Symptomatic expression of depressive disturbances: 1) differ with age (somatic complaints and relational isolation in younger children, loss of self-esteem in adolescents) and 2) are different according to sex in adolescents (somatic preoccupations in girls, social problems in boys). PMID- 7878141 TI - [New drug policies: the Geneva example]. AB - As a consequence of the negative medical social effects of illicit drug use a certain number of countries, during the eighties, have chosen to rethink their therapeutical strategies which were mainly aimed at instoring rapid abstinence. Risk-reduction strategies are varied, including distribution of syringes, substitutive strategies and cultural modification of the drug-addicted representations. Such substantial modifications lead to reflections on both national and international legal systems. PMID- 7878142 TI - [Passage into paternity: a clinical approach]. AB - In this paper the authors discuss the problematics of the phenomenon of going into fatherhood within a transient Society, Greece, that was framed in the course of a clinical research. The main goal of this study was to describe the social psychological dynamics and long term dimension of the phenomenon through analysis of interviews with young men becoming fathers for the first time in their lives. The theoretical framework and the social psychological context of the research are presented, together with the analyses of two accounts by fathers interviewed each three times, before and after their child's birth. This clinical material serves as an illustration of the psychodynamic processes of going into fatherhood and points to two dimensions: one is intrapersonal (essentially marked by identifications to parental images) and the other interpersonal (essentially marked by the relationships with the partner). Analysis of the subjects' affects and representations shows that resolution of conscient and unconscious conflicts which takes place during the going into fatherhood are dependent on the process of disengagement from the family of origin and on the ability of both partners to construct a conjugal space. Men (and fathers-to-be) when faced with the situation may either confine themselves to culturally established schemes or/and their own history, or find a new meaning to their personal and relational life. PMID- 7878143 TI - [Some difficulties in the "paternalization" process in medically assisted reproduction]. AB - Based on the observation of a child born by IAD, suffering of depression and presenting a school phobia, the author discusses the feeling of impotency experienced by the legal father. In another case, the grand-father-to-be is ready to donate his sperm so as to avoid issues on genetics: it is doubtful that such birth conditions would permit a healty organization of fatherhood. Included in the article are references on the literature concerning psychopathology of children born by IAD. PMID- 7878144 TI - [Attachment, a theory to rediscover and complete]. AB - Thirty five years after the publication of Bowlby's founding articles (1957 and 1958), what relevance might the theory of attachment still have for the conceptual and methodological apparatus used by the psychologists who study emotional development of the young? That question is addressed throughout this article through a historic-critical review and leads to formulating two tentative responses. In the first part are shortly presented the contributions which have brought precisions, supported and prolonged the leader's propositions. In the second part we attempt to partially reconceptualize the process and behavior of attachment, following the recent suggestions of Bowlby and Ainsworth. Two cases of parent-infant interactions serve as empirical illustrations for this new perspective. PMID- 7878145 TI - [Comparison of psychophysiological states in patients with bipolar affective disorder and healthy subjects]. AB - It has been proposed a method for description of psychophysiological tension by simultaneous evaluation of heart rate, respiration and muscle tonus. Summary index (W) has been elaborated. On the basis of that index subjects with depressions phase of bipolar affective disorder were found to essentially differ from healthy subjects. PMID- 7878146 TI - [Reactivity and the need for stimulation in affective syndromes]. AB - Twelve patients with endogenous depression and 13 health persons were investigated with the questionnaire FCZ KT (for measurement of temperament) and computerized Wiener Testsystem (for the evaluation of cognitive functions). Depressive patients expressed higher level of reactivity and a lower need for stimulation in comparison to a control group. In terms of temperamental characteristics (by FCZ KT test) the depressive group was less alert, more perseverative, less sensitive and more fatigued than the control group. The group with depression scored higher on scales measuring anxiety as a state and as a trait. No significant differences between the groups in physiological parameters measured by Wiener Testsystem were found. PMID- 7878147 TI - [Suicidal attempts among soldiers]. AB - The authors conducted the analysis of 93 case histories of soldiers who were subjected to clinic observation in two four-year periods owing to suicide attempts. It was shown that the most frequent psychiatric diagnoses following observation were disadaptative syndromes (36.6%) and abnormal personality (32.3%). The reason for suicide attempts of the soldiers were mostly adjustment difficulties (45.2%) and conflicts of premature release from army (79%). PMID- 7878148 TI - [Analysis of clinical data on alcoholics: a 3-year follow-up study]. AB - 74 male alcoholics participated in a three year prospective study. Data were collected four times: at admission (for the detoxification) and 1, 2 and 3 years after discharge. Patients were divided into groups according to drinking behaviour. Abstainers and relapsers who had been followed up for three years were compared with treatment variables in an attempt to separate those factors which would be predictors of outcome type. Our results indicate that for alcoholics, having an additional diagnosis of antisocial personality or drug dependence was associated with poor outcome. We failed to find a relationship between the history of alcohol dependence (manner of drinking, age of onset etc.) and clinical course. Our results suggest that symptoms of depression and anxiety, observed during a period of detoxification were gradually lowered according to the time of abstinence. Abstinence-status at a 3 year follow-up was associated with regular out-patients treatment especially during the first year after discharge. PMID- 7878149 TI - [Ethical, legal and medical problems concerning ECT administration]. AB - Electroconvulsive treatment is a serious and effective biological therapy of current psychiatry which is associated with a certain risk. Treatment with ECT creates a series of problems of a ethico-moral nature which may be solved only in part by the gaining of informed consent of the patient for the treatment procedure. The procedure of gaining "informed consent" in relation to ECT ought to find its regulation in specific acts of the law. The problems concerned with ECT as with other problems in psychiatry should be demistified and become an element of general knowledge available to the whole of society. PMID- 7878150 TI - [A new view of the evaluation of alcohol withdrawal and alcohol dependence]. AB - This study was designed to evaluate 21 alcohol dependent male individuals during withdrawal syndrome. The intensity of withdrawal symptoms was measured using Sandowal-Wang scale. The level of blood serum prolactin was measured twice a day (8 a.m. and 8 p.m.) on the lst, 3rd, 7th, 14th, 21st day of the study. Also the depth and the time of the development of dependence were evaluated using DSM-III R criteria, alcohol dependence (WGU) and presence of dependence symptoms scale (WWO). It was establish that WGU, WWO and DSM-III-R criteria, separated similar groups of patients with the same depth of dependence clinical symptoms and prognosis. This study revealed a negative correlation between intensity of withdrawal symptoms and PRL levels in blood serum on the 1st day of abstinence. PRL levels increased from the 3rd to the 21st day of the study. Ethanol withdrawal symptoms intensity index was positively correlated with WGU. PMID- 7878151 TI - [Homicide in affective states and the problem of responsibility]. AB - The penal code dated April 19th 1969 allows for three privileged types of manslaughter: manslaughter under strong emotional disturbance (art. 148 sections 2), infanticide (art. 149) and euthanasia for request (art. 150). The first two types of manslaughter are the discussed the third one is neglected because only the general problems of soundness of mind, non-accountability and greatly diminished accountability (art. 25 penal code) refer to them. In the situation when strong emotional disturbance exists (so called physiologically conditioned emotional disturbance) from art. 148 sections 2 penal code and one of the mentioned states mentioned in art. 25 penal code (mental deficiency, mental disease, other mental disorders) results in greatly diminished accountability and the cumulative qualification from art. 148 sections 2 and art. 25 sections 2 penal code will be admissible. As far as infantcide is concerned, the following opinion has been expressed that physiologically proper childbirth does not cause disconnection or restriction of soundness of mind. But in the case of psychological disorders such possibility cannot be excluded. The author postulates a wide participation of experts in psychology and psychiatry in cases prosecuted under art. 148 sections 2 penal code and art. 149 penal code. PMID- 7878152 TI - [The influence of the type and level of aggression on homicidal behaviour]. AB - A comparative analysis carried out on the type and level of aggressiveness in 105 perpetrators of homicide shows that in those assessed there is a lack of homogeneity in the personality structure, the developmental factors which determine the more stable mechanism of behavior, the course and the level of socialization, and the depth of psychopathological disturbance. Aggression understood as a permanent readiness to react to external stimuli and situations by using open and direct aggression characterizes the perpetrator with a disturbed socialization process. A deep level of hostility of the subjects seems to be associated with a weak influence of the personality structure and mechanisms in their basic regulatory and adaptive functions and an anxious attitude in respect of the social surroundings. Non-aggressive perpetrators of homicide mostly act under the influence of significant stronger psychopathological factors (delusions and hallucinations) or very strong pressure of situational factors not related to their personality. Homicidal behavior is thus an effect of very different internal variables and situational factors. PMID- 7878153 TI - [The importance of examining genetic polymorphism of drug oxidation in psychiatry]. AB - The paper describes: 1. Drug oxidation process. 2. Cytochrome P-450 Isozymes. 3. Genetic polimorphism of drug oxidation. 4. Spartein test. Metabolic ratio, extensive and poor metabolizers. 5. Cytochrom P-450 and drug metabolism. 6. Inhibition of drug oxidation process and inhibitors of CYP450. 7. Influence of CYP450 genetic polimorphism on development of diseases. 8. Clinical value of examining the genetic polimorphism of drug oxidation in psychiatry. PMID- 7878154 TI - [Assessment of threatening behaviors in patients admitted to mental hospital]. AB - Imminent threat presented by patients admitted to mental hospital was studied. The research data came from a questionnaire filled out by psychiatrists on duty at the time of admission. The study was carried out during 3 months in seven mental hospitals. It concerns only 1001 patients assessed by psychiatrists as imminently threatening. These assessments were compared with Lessard's criteria of dangerousness. Two types of assessments were made; type A--consistent with Lessard and type B not-consistent. Results obtained indicate that every third assessment belonged to type B i.e. could be seen as imminently threatening. Our findings show that psychiatrists taking part in the study were inclined to unduly broad or unduly discretional assessment of imminent threat. PMID- 7878155 TI - [Debrisoquine hydroxylation test as an example of new possibilities of research in psychopharmacology]. AB - About 5-10% of European white population has a genetically determinant defect of the CYP2D6, one of the enzymes of cytochrome P-450. This defect leads to the impaired metabolism of many drugs including various psychopharmacological agents. The measurement of the hydroxylation of debrisoquine is a laboratory test which allows to identify such an individual. Patients who show an impaired hydroxylation of debrisoquine usually demonstrate severe side effects and poor outcome of psychopharmacotherapy. This depends on whether the administered drug is metabolized the same way as debrisoquine, i.e. in the presence of CYP2D6. The diagnosis of the phenotype of debrisoquine hydroxylation before treatment may allow to select the group of poor metabolizers. This diagnosis can help to identify the appropriate treatment for those patients, i.e. the selection of either a drug which is not metabolized in the presence of CYP2D6 or an alternative form of therapy. PMID- 7878156 TI - [Agranulocytosis in the course of clozapine treatment]. AB - Clozapine is highly effective for drug resistant schizophrenia, it does not cause any extrapiramidal side effects, but involves a high risk of agranulocytosis with fatal outcome. The pathogenesis of agranulocytosis is not clear but genetic factors, as well as immunological and toxic mechanism may play an important role. Since the introduction of the monitoring system of leucocytosis for every patient an increasing number of agranulocytosis cases are being registered. Owing to the monitoring system, an immediate discontinuation of the drug, and the initiation of appropriate treatment the number of cases with fatal outcome is not growing in spite of the increasing number of patients treated with clozapine. In the described patient with chronic schizophrenia and ulcerative disease, agranulocytosis disappeared within 7 days after discontinuation of the drug. Three months later the patient died because of perforation of a duodenal ulcer. A negative influence of closapine on ulcerative disease should by considered, but the authors have not found any information on this topic in the literature. PMID- 7878157 TI - [Own experiences (1989-1994) in the treatment of adolescent schizophrenic paranoid syndromes with Leponex produced by Sandoz company]. AB - 31 patients with schizophrenic adolescent paranoid syndrome were treated by Leponex-Sandoz after the establishing of the therapeutic indications. We did not observe any considerable side effects. We observed the regression of positive symptoms at 19-day of the treatment and the regression of negative symptoms at 23 day of the therapy. We conclude that Leponex-Sandoz is effective and safe medication in the treatment of adolescent schizophrenic paranoid syndrome. PMID- 7878158 TI - [Factors influencing the clinical picture, course and effectiveness of therapy in patients with manic-depressive psychoses]. AB - The long lasting (5-8 years) clinical observations of 496 patients suffering from manic-depressive psychoses had allowed the authors to distinguish some factors which influence (in a positive and negative way) the clinical features and therapeutic effectiveness as well as to follow the origin of psychoses. The attached specification of these factors is not complete, further tests and investigations are needed. PMID- 7878159 TI - [A case report of cyclic psychosis]. AB - Cycloid psychoses have a special position in psychiatric classification. Usually they are listed among atypical psychoses, located between the group of schizophrenias and affective psychoses. Nevertheless, there are indications for nosological differentiation of cycloid psychoses from other psychotic conditions. The case of cycloid psychosis of a 38 year old woman with two severe psychotic episodes of mixed, paranoid and affective symptomatology is described. Among the characteristic features of psychotic episodes were acute onset, severe but short course of the episodes and the lack of residual/defect symptoms at outcome. On the basis of this case the differential diagnosis of cycloid psychoses is discussed. PMID- 7878160 TI - Preemption effects in visual search: evidence for low-level grouping. AB - Experiments are presented showing that visual search for Mueller-Lyer stimuli is based on complete configurations rather than component segments. Segments easily detected in isolation were difficult to detect when embedded in a configuration, indicating preemption by low-level groups. This preemption--which caused stimulus components to become inaccessible to rapid search--was an all-or-nothing effect and so could serve as a powerful test of grouping. It is shown that these effects are unlikely to be due to blurring by simple spatial filters at early visual levels. It is proposed instead that they are due to more sophisticated processes that rapidly blind contour fragments into spatially extended assemblies. These results support the view that rapid visual search cannot access the primitive elements formed at the earliest stages of visual processing; rather, it can access only higher level, more ecologically relevant structures. PMID- 7878161 TI - Planning reaches by evaluating stored postures. AB - This article describes a theory of the computations underlying the selection of coordinated motion patterns, especially in reaching tasks. The central idea is that when a spatial target is selected as an object to be reached, stored postures are evaluated for the contributions they can make to the task. Weights are assigned to the stored postures, and a single target posture is found by taking a weighted sum of the stored postures. Movement is achieved by reducing the distance between the starting angle and target angle of each joint. The model explains compensation for reduced joint mobility, tool use, practice effects, performance errors, and aspects of movement kinematics. Extensions of the model can account for anticipation and coarticulation effects, movement through via points, and hierarchical control of series of movements. PMID- 7878162 TI - Implicit social cognition: attitudes, self-esteem, and stereotypes. AB - Social behavior is ordinarily treated as being under conscious (if not always thoughtful) control. However, considerable evidence now supports the view that social behavior often operates in an implicit or unconscious fashion. The identifying feature of implicit cognition is that past experience influences judgment in a fashion not introspectively known by the actor. The present conclusion--that attitudes, self-esteem, and stereotypes have important implicit modes of operation--extends both the construct validity and predictive usefulness of these major theoretical constructs of social psychology. Methodologically, this review calls for increased use of indirect measures--which are imperative in studies of implicit cognition. The theorized ordinariness of implicit stereotyping is consistent with recent findings of discrimination by people who explicitly disavow prejudice. The finding that implicit cognitive effects are often reduced by focusing judges' attention on their judgment task provides a basis for evaluating applications (such as affirmative action) aimed at reducing such unintended discrimination. PMID- 7878163 TI - On the status of inhibitory mechanisms in cognition: memory retrieval as a model case. AB - Theories of cognition frequently assume the existence of inhibitory mechanisms that deactivate mental representations. Justifying this assumption is difficult because cognitive effects thought to reflect inhibition can often be explained without recourse to inhibitory processes. This article addresses the uncertain status of cognitive inhibitory mechanisms, focusing on their function in memory retrieval. On the basis of a novel form of forgetting reported herein, it is shown that classical associative theories of interference are insufficient as accounts of forgetting and that inhibitory processes must be at work. It is argued that inhibitory processes are used to resolve computational problems of selection common to memory retrieval and selective attention and that retrieval is best regarded as conceptually focused selective attention. PMID- 7878164 TI - Caffeine and smoking: subjective, performance, and psychophysiological effects. AB - The effects of caffeine and smoking on cognitive performance, subjective variables, heart rate, and EEG were assessed in two sessions. In one session, subjects received caffeine (2.5 mg/kg bodyweight), while in the other they received placebo. In both sessions they smoked a cigarette (8 cued puffs) having a nicotine yield of 1.2 mg. Caffeine produced an increase in self-reported muscular tension and tended to increase anxiety and delta magnitude. Smoking facilitated performance of a paper-and-pencil math task and increased heart rate. Smoking also appeared to produce cortical activation as indexed by decreased right frontal delta, decreased right centro-parietal theta, globally increased alpha, and increased centro-occipital/decreased posterior-temporal beta 1. Smoking also increased central/decreased posterior-temporal beta 2. Smoking and caffeine did not interact for any measure, suggesting that the epidemiological link between smoking and coffee drinking may have a non-pharmacological basis. PMID- 7878165 TI - Cardiovascular reactivity, Type A behavior, and coronary heart disease: comparisons between myocardial infarction patients and controls during laboratory induced stress. AB - Cardiovascular responses to a series of laboratory stressors were examined in middle-aged Type A and Type B men. The subjects were 30 patients with diagnosed myocardial infarction (NYHA Class 1) and 26 age-matched healthy controls. All subjects were nonsmokers in the normotensive range, and none were on medication. Blood pressure, heart rate, forearm blood flow and resistance, and impedance cardiography-determined response variables were obtained during performance and recovery periods of both mental and physical tasks. The patients showed elevated reactivity in systolic blood pressure and cardiac output and prolonged systolic time ratio during mental stress tasks and elevated total peripheral resistance and lower cardiac output and stroke volume during physical tasks, as compared with control subjects. Thus, the difference in blood pressure reactivity between patients and controls appeared to be primarily dependent on the vascular component during physical tasks, whereas the mental tasks promoted a hemodynamic response pattern more consistent with beta adrenergic activation. Type A men, irrespective of coronary status, showed larger systolic and diastolic blood pressure response to both mental and physical stress than did Type B men. PMID- 7878166 TI - Generalization of the orienting response to significant stimuli: the roles of common and distinctive stimulus components. AB - This study focused on the effects of common and distinctive stimulus components on the generalization of the orienting response (OR) to significant stimuli. Compound pictorial stimuli were used as the relevant items memorized by the subjects. Skin conductance responses were measured during the subsequent presentation of a stimulus sequence that included a test stimulus that shared some common components with the relevant one. The two types of stimulus components (common and distinctive) were independently manipulated. As predicted by the feature-matching theory, both types of features affected OR generalization, but the distinctive components effect was due mainly to a large decline in OR with the introduction of the first distinctive component. As hypothesized, no interaction was observed between the effects of common and distinctive components. Contrary to expectations, similar OR generalization was obtained regardless of whether the test stimulus was constructed by deleting stimulus components from the relevant stimulus or by adding components to that stimulus. PMID- 7878167 TI - Neural mechanisms of visual selective attention. AB - Visual selective attention improves our perception and performance by modifying sensory inputs at an early stage of processing. Spatial attention produces the most consistent early modulations of visual processing, which can be observed when attention is voluntarily allocated to locations. These effects of spatial attention are similar when attention is cued in a trial-by-trial, or sustained, fashion and are manifest as changes in the amplitudes, but not the latencies, of evoked neural activity recorded from the intact human scalp. This modulation of sensory processing first occurs within the extrastriate visual cortex and not within the striate or earlier subcortical processing stages. These relatively early spatial filters alter the inputs to higher stages of visual analysis that are responsible for feature extraction and ultimately object perception and recognition, and thus provide physiological evidence for early precategorical selection during visual attention. Moreover, the physiological evidence extends early selection theories by providing neurophysiologically precise information about the stages of visual processing affected by attention. PMID- 7878168 TI - Functional neuroanatomy of visually elicited simple phobic fear: additional data and theoretical analysis. AB - We investigated central nervous system correlates of simple phobic fear. Regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) in eight volunteers with symptomatic spider phobia that were exposed to visual phobogenic and neutral stimuli. Diazepam (0.1 mg/kg body weight i.v.) or placebo was administered under double-blind conditions after initial PET scans. The PET scans were then repeated. The presence of fear was confirmed by rating procedures and increased number of nonspecific electrodermal fluctuations and by higher heart rate during phobic than during neutral stimulation. Phobic as compared to neutral stimulation elevated the regional to whole brain (relative) CBF in the secondary visual cortex but reduced relative rCBF in the hippocampus, prefrontal, orbitofrontal, temporopolar, and posterior cingulate cortex. Diazepam treatment did not affect the relative rCBF or the subjective or physiological fear indices. The observed rCBF pattern replicates our previous findings in snake phobics (M. Fredrikson et al. [1993] Psychophysiology, 30, 127-131; G. Wik et al. [1993] Psychiatry Research (Neuroimaging), 50, 15-24) and indicates that fear and anxiety affect cortical areas outside the classic limbic system areas. PMID- 7878169 TI - The effects of running, environment, and attentional focus on athletes' catecholamine and cortisol levels and mood. AB - This study was designed to examine some of the psychoneuroendocrine effects of exercise-induced emotional experiences and the mediating effects of environmental setting and subjects' attentional focus. Trained runners were tested during an outdoor run and two indoor treadmill running conditions. Excretions of catecholamines and cortisol significantly increased after all running conditions but not after a control condition. Results indicate that patterns of endocrine and concomitant emotional change through exercise differ when environmental setting and attentional focus are altered in such a way that a normally pleasant task such as running becomes tedious and negatively evaluated. These findings support the notion that setting, attention, and cognitive appraisal may alter the emotional experience associated with physical exercise. PMID- 7878170 TI - Processing of auditory deviants with changes in one versus two stimulus dimensions. AB - Auditory event-related potentials (ERPs) in response to 50-ms tones were recorded from the human scalp. A standard stimulus (p = .88) and three different deviants were randomly presented via earphones. There were two one-dimensional deviants (one frequency and one location deviant) and one two-dimensional deviant, with changes in both frequency and location. In one condition, subjects read a book and ignored the auditory stimuli, whereas in another condition they tried to discriminate deviants from standards. In the ignore condition, the two dimensional deviant elicited an enhanced mismatch negativity (MMN) as compared with the MMNs elicited by the one-dimensional deviants. The temporal and the topographic distributions of the two-dimensional MMNs could be modeled by adding the one-dimensional MMNs. This activity of the MMNs probably results from the independent activity of separate neural populations generating the frequency and the location MMN. In the attend condition, the deviance-related ERP effects were not additive in the N2b and P3 range, implicating that the neural processes involved in the conscious detection of changes in location and frequency were not independent. PMID- 7878171 TI - Internal consistency reliability of resting EEG power spectra in schizophrenic and normal subjects. AB - The reliability of resting electroencephalogram (EEG) power spectra was assessed for 49 normal and 44 schizophrenic subjects. We specifically examined internal consistency reliability to determine how much EEG data are necessary to ensure small measurement error. Twenty-one 8-s epochs of resting EEG were collected from each subject from site Cz. Epochs containing artifacts or blinks were eliminated. Power was computed in the bands delta (0.125-3 Hz), theta (3.125-8 Hz), alpha (8.125-13 Hz), beta1 (13.125-20 Hz) beta 2 (20.125-25 Hz) and beta 3 (25.125-30 Hz). Internal consistency was computed using coefficient alpha (Cronbach, 1951). Results for both groups indicated that eight artifact-free epochs of data were sufficient to give a coefficient alpha value of around .9. The schizophrenic and normal groups did not differ with respect to coefficient alpha. The proportion of artifacts in the data from the schizophrenics indicated that to obtain eight artifact-free epochs from members of each group, 40% more data would be required from the schizophrenics. PMID- 7878172 TI - Startle potentiation during anticipation of a noxious stimulus: active versus passive response sets. AB - The startle reflex response increases during aversive stimulus processing. This study examined whether differing response sets affected startle potentiation during anticipation of an aversive event. Two groups received a noxious noise blast following a 6-s warning cue. Subjects in the active group could press a switch to stop the noise; yoked passive subjects received the same noises with no control. Subjects in a yoked control group heard a soft tone following cue offset. Acoustic startle probes were presented during some of the warning periods and during some of the intertrial intervals. The major finding was that the active and passive groups did not differ in startle potentiation. In comparison with controls, startle reactions for both groups were larger and faster during the warning cue than between trials. The results suggest that the startle reflex indexes defensive response mobilization independently of specific task demands. PMID- 7878173 TI - Is elevated blood pressure level associated with higher cardiovascular responsiveness in laboratory tasks and with response specificity? AB - Cardiovascular responsiveness and response specificity were investigated in male students, 48 with moderately elevated blood pressure (systolic blood pressure [SBP] > 140 mmHg and/or diastolic blood pressure [DBP] > 90 mmHg), 31 with mildly elevated blood pressure, and 57 with normal blood pressure. The behavioral tests and physically demanding tasks in the laboratory included mental arithmetic, free speech condition, cold pressor test, upright tilt, and ergometer exercise. Subjects with elevated blood pressure differed in baseline, task, and recovery levels of SBP, DBP, and heart rate. There were no significant effects in task baseline differences or in residualized change scores. However, a positive initial-value dependency (LIV) in blood pressure responses was found: elevated blood pressure is associated with a larger increase under task conditions. Response scaling that employed reliability estimates and true difference scores indicated higher responsiveness in subjects with moderately elevated blood pressure and, thus, are in accordance with the positive LIV as compared with response measures based on task-baseline differences or residualized change scores. Findings from the specificity analysis indicated a higher incidence of SBP responders, that is, subjects with maximum response in SBP, among subjects with elevated blood pressure. Some of the inconsistencies in the literature with respect to blood pressure responsiveness and heart rate level in individuals with borderline hypertension may be attributed to the specific method of response scaling and to insufficient habituation to the setting and measurement. PMID- 7878174 TI - Nightcap: laboratory and home-based evaluation of a portable sleep monitor. AB - In this paper, we describe the first field tests of a home-based sleep monitoring system, the Nightcap, which uses eyelid and body movement sensors to discriminate wake, NREM, and REM sleep automatically. Ten normal young adults were studied in the sleep laboratory and at home to allow comparison of Nightcap-derived measures with those obtained by traditional polysomnography. The agreement between the two techniques was 87% based on 1-min epochs--93% for NREM, 80% for REM, and 72% for wake. When the values for sleep latency, REM latency, wake time, NREM time, and REM time calculated from polysomnograph records were compared with the values calculated from Nightcap data, no significant differences were seen. In cases of extremely poor sleep, objective sleep efficiency estimates correlated well with subjective reports, suggesting that the Nightcap is sensitive to clinically relevant changes in the quality of sleep. This new device should prove useful to researchers wishing to study the psychophysiology and pathophysiology of sleep in more naturalistic and cost-effective paradigms than possible in the traditional sleep laboratory. PMID- 7878175 TI - New directions for ECT research. Introduction. PMID- 7878176 TI - Indications for the use of ECT. PMID- 7878177 TI - Central issues regarding the mechanisms of action of electroconvulsive therapy: directions for future research. AB - Over 100 theories have been offered to account for the therapeutic effects of electroconvulsive therapy (ECT). The findings that technical factors in treatment administration strongly determine the magnitude of antidepressant effects contradict a number of psychological explanations that focus on placebo effects and patient expectations. The independence of therapeutic and adverse cognitive side effects implies an independence of mechanisms. Biological investigation of mechanisms has been impeded by the belief that therapeutic effects are an intrinsic outcome of seizure elicitation. However, recent research has contradicted long-held conceptions of the necessary and sufficient conditions for ECT's antidepressant effects. The recognition that generalized seizures that lack therapeutic properties can be reliably elicited provides new opportunities for examining the neurophysiological and biochemical determinants of efficacy. Neurophysiological and biochemical theories are described and future research directions are outlined. PMID- 7878178 TI - The mode of action of ECT. PMID- 7878179 TI - Treatment optimization with ECT. AB - Although electroconvulsive therapy (ECT) is considered to be an effective and safe treatment, as with any treatment, both therapeutic outcome and adverse effects can be expected to vary considerably across patients. It is incumbent upon the practitioner to be aware of factors that serve to influence the benefits and risks associated with this treatment modality. This article provides a brief, clinically oriented overview of many of these factors, including those that may be useful in response prediction, as well as technical modifications of the ECT procedure itself. In addition, a number of suggestions are made concerning promising future avenues of research in this area. PMID- 7878180 TI - Animal studies of electroconvulsive therapy: foundations for future research. AB - Since the introduction of electroconvulsive therapy (ECT) in 1938, research studies in animals have made significant contributions to the clinical practice of ECT. In our search for the underlying mechanism by which ECT exerts its therapeutic and adverse effects, animal studies have yielded additional clues. This paper reviews existing animal literature on electroconvulsive seizures (ECS). It emphasizes ways in which animal data informs our clinical practice and illuminates possible mechanisms of ECT's actions. Finally, recommendations are made for future studies in ECS. PMID- 7878181 TI - Elucidation of biochemical basis of the antidepressant action of electroconvulsive therapy by human studies. AB - A variety of direct and indirect human studies indicate that electroconvulsive therapy (ECT) enhances transmission in a number of key transmitter systems in the brain. These include the noradrenergic system, the serotonergic system, and the GABAergic and dopaminergic systems. On the other hand, ECT probably reduces cholinergic transmission. The enhanced transmission effects have been related to the antidepressant effect of ECT, whereas the cholinergic effect has been attributed to its effects on memory and cognition as well as depression. This paper will briefly review the research methodologies and results from clinical studies of neurotransmitter effects of ECT. Promising future directions of research will be indicated. PMID- 7878182 TI - ECT methodologic issues. PMID- 7878183 TI - Neuropsychology and ECT: past and future research trends. AB - Past research focused on characterizing the cognitive deficits caused by ECT, understanding their causes, and defining ways of ameliorating the deficits. Future research includes the following recommendations. IN CHARACTERIZING THE DEFICITS: more accurately defining the time course to recovery; finding out whether specific memory tasks and specific patients show long-lasting effects; and defining specific components of memory and non-memory deficits (e.g., associative memory, incidental everyday memory, inattention). IN UNDERSTANDING THE CAUSES: determining whether seizure activity in certain brain structures is associated with specific cognitive deficits; finding out in which ways electric dose, electrode placement, seizure duration, and seizure threshold interact in causing the deficits; evaluating the effects of mediating variables such as blood pressure rise; and assessing the influence of background variables such as age, sex, and brain abnormality. IN AMELIORATING THE DEFICITS: continuing the search for effective medication; defining ways of reducing the number of treatments (twice weekly ECT, caffeine or thyroxine modified treatment); and manipulating dose in relation to electrode placement. PMID- 7878184 TI - Patient attitudes toward electroconvulsive therapy. AB - Electroconvulsive therapy (ECT), a safe and effective treatment for major depression, has been more harshly criticized than any other psychiatric treatment. Despite widespread negative public opinion, clinical impressions that are supported by limited empirical data suggest that patients who benefit from ECT do not share these negative sentiments. This study surveyed attitudes toward ECT in 78 depressed inpatients, twice during hospitalization and at 6 months after discharge, using a semi-structured interview. Significantly more ECT treated patients (n = 56) were favorable about ECT, compared to depressed patients (n = 22) never treated with ECT, both at pretreatment (chi square = 8.4, df = 1, p < .01) and at post-treatment (chi square = 12.5, df = 1, p < .01). Favorable attitudes were maintained after 6 months. ECT-treated patients, initially uncertain or negative about ECT, changed to a favorable attitude after completing treatment. Ninety-eight percent of ECT-treated patients said they would agree to ECT if they became depressed again. PMID- 7878185 TI - The role of structural brain imaging in ECT. PMID- 7878186 TI - The thyroid and electroconvulsive treatment. PMID- 7878187 TI - Effects of electroconvulsive therapy on the CRH-ACTH-cortisol system in melancholic depression: preliminary findings. AB - Hypercortisolism is one of the most consistent biological abnormalities seen in patients with major depression, particularly the melancholic subtype. We present preliminary data regarding the effects of electroconvulsive therapy (ECT) on urinary-free cortisol (UFC) excretion and on the secretion of its principal regulatory hormone, corticotropin-releasing hormone (CRH), into the cerebrospinal fluid (CSF) of patients with major depression. Our preliminary results indicate that, while acute elevations in UFC may occur with the initiation of ECT or other antidepressant treatments, successful treatment with ECT is associated with a reduction in both UFC excretion and the diurnal pattern of CSF immunoreactive CRH levels. These findings are compatible with data in experimental animals that show reductions in hypothalamic CRH expression and pituitary-adrenal function with long-term antidepressant treatments. PMID- 7878188 TI - Electroconvulsive therapy and Parkinson's disease: the case for further study. PMID- 7878189 TI - Continuation therapy following ECT: directions for future research. AB - The use of electroconvulsive therapy (ECT) in major depression typically involves sequential treatment trials. Most patients fail one or more antidepressant medications before receiving ECT, and patients who respond to ECT usually receive continuation pharmacotherapy. Indeed, ECT is the only somatic treatment in psychiatry that is typically discontinued when it is found to be effective. This paper reviews the relations of medication resistance during the acute episode to short-term response to ECT and the use of continuation pharmacotherapy and continuation ECT as methods to prevent relapse. Recent research contradicts the long-held view that failure to respond to adequate trials of anti-depressant medication has no impact on response to ECT. Further, recent research has documented high relapse rates following ECT and has questioned the efficacy of using traditional antidepressant medications for continuation pharmacotheraphy when patients have established resistance to those same agents during treatment of the acute episode. Continuation ECT has strong potential as a method to prevent early relapse, but its efficacy has never been demonstrated in controlled research. In each of these areas, detailed recommendations are given for future research. PMID- 7878190 TI - Comparison of the prostaglandin E (EP) receptor of human neutrophils and HL-60 cells differentiated with DMSO. AB - Human promyelocytic leukaemic HL-60 cells can be differentiated with DMSO to become neutrophil-like. In this study, the prostanoid receptors linked to adenylate cyclase have been compared in human neutrophils and in differentiated HL-60 cells. Both cell types appear to express EP2 receptors as recognised by the ability of EP2 agonists and not EP1 or EP3 agonists to increase cell cyclic AMP levels, and the finding that the increase in cyclic AMP induced by PGE2 was not blocked by the EP4 receptor antagonist AH 23,848 (30 microM). Neither cell type appears to express receptors for PGI2, but human neutrophils and not differentiated HL-60 cells express receptors for PGD2. In addition, human neutrophils may contain EP3 receptors linked to a reduction in cyclic AMP levels. The lack of other prostanoid receptors coupled to adenylate cyclase in HL-60 cells suggests that these cells may provide a useful starting point for the cloning of the EP2 receptor. PMID- 7878191 TI - Effect of alkaline phosphatase on thromboxane mimetic induced platelet activation. AB - Recently it has been reported that alkaline phosphatase selectively inhibited thromboxane mimetic induced platelet aggregation and secretion suggesting that the phosphorylation state on the platelet surface may be important for thromboxane induced platelet activation. We report here studies attempting to elucidate the mechanism of action of alkaline phosphatase. Washed human platelet aggregation induced by the thromboxane mimetic IBOP was completely abolished when incubated with alkaline phosphatase (1 unit/ml) for 5 min. The effect was inhibited by co-incubation with 5mM phosphate. Binding studies using [125I]BOP showed that neither the affinity of IBOP for the receptor (control: 9.2 +/- 2.1 nM, alkaline phosphatase: 7.9 +/- 1.8 nM) nor the Bmax (control: 1780 +/- 320 sites/plt. alkaline phosphatase: 1920 +/- 290 sites/plt) were effected by alkaline phosphatase treatment. GTPase activity was measured in platelet membranes treated with and without alkaline phosphatase as measured by IBOP induced hydrolysis of [gamma-32P]GTP. The EC50 values for IBOP induced GTPase were similar whereas the maximum amount of released Pi in the control membranes was more than two fold greater than in alkaline phosphatase treated membranes. These studies suggest that thromboxane induced platelet activation may be dependent upon the phosphorylation state of the thromboxane receptor and/or closely associated protein. PMID- 7878192 TI - Actions of the E2-isoprostane, 8-ISO-PGE2, on the platelet thromboxane/endoperoxide receptor in humans and rats: additional evidence for the existence of a unique isoprostane receptor. AB - D2/E2-isoprostanes, are a recently discovered series of novel prostaglandin-like compounds that are produced in vivo as products of free radical-catalyzed peroxidation of arachidonic acid independent of the cyclooxygenase enzyme. One of the E-ring compounds expected to be produced in abundance by this mechanism, 8 iso-prostaglandin E2 (8-iso-PGE2), is a potent renal vasoconstrictor in the rat, and this effect can be abrogated by the thromboxane/endoperoxide (TxA2/PGH2) receptor antagonist SQ29548, suggesting that 8-iso-PGE2 exerts these effects by interaction with this receptor in the vasculature. Nonetheless, it has recently been suggested that 8-iso-PGE2 induces vasoconstriction by interaction with a unique receptor similar to, but distinct from, the TxA2/PGH2 receptor. Because this issue has not been resolved, we carried out studies to further examine the interaction of this compound with the TxA2/PGH2 receptor on human and rat platelets. Only at concentrations of 10(-5) M or greater did 8-iso-PGE2 induce human platelet aggregation. The aggregation was unaffected by indomethacin but was inhibited by the TxA2/PGH2 receptor antagonist SQ29548. Conversely, 8-iso PGE2 inhibited the thromboxane receptor agonists U46619 (10(-6) M) and IBOP (3.3 x 10(-7) M) with an IC50 of 5 x 10(-7) M and 5 x 10(-6) M, respectively. 8-iso PGE2 also inhibited platelet aggregation induced by arachidonic acid but not by ADP. Similarly in rat platelets, 8-iso-PGE2 alone. PMID- 7878193 TI - Prostaglandin F2 alpha-induced release of oxytocin from ovine corpora lutea in vitro. AB - Prostaglandin (PG)F2 alpha, in the dose range 1-10(4) nM, failed to elicit oxytocin secretion in vitro from ovine luteal tissue on day 12 of the estrous cycle (estrus = Day 0), during a 60 minute period. Preincubation of luteal slices for 6 hours prior to treatment suggested that tissue desensitization due to the release of endogenous prostaglandins by tissue preparation is not responsible for this lack of response. However, in luteal tissue collected on day 6 of the ovine estrous cycle, PGF2 alpha stimulated oxytocin release in a dose-dependent manner. This apparent change in sensitivity of the ovine corpus luteum in vitro may be due to a combination of a reduction in the luteal oxytocin available for release and saturation of PGF2 alpha receptors in the more mature tissue. PMID- 7878194 TI - Prostaglandins and sex steroids from corpora lutea of pregnant mares. In vitro studies. AB - To delineate endocrine mechanisms regulating equine luteal function and the possible functional differences between one month and three month corpora lutea of pregnancy (CL), the in vitro basal releases of prostaglandin F (PGF), prostaglandin E2 (PGE2), progesterone, and 17 beta-estradiol by one and three month CL of pregnant mares were evaluated. In addition, the in vitro effects of PGF2 alpha PGE2, progesterone and 17 beta-estradiol on synthesis of prostaglandins (PGs) and sex steroids were studied. PGF, PGE2, and 17 beta estradiol secretion was higher in one month than in three month CL, while progesterone was secreted similarly by both types of CL. PGE2 treatment decreased 17 beta-estradiol in one month CL; progesterone increased PGE2 in one and three month CL; 17 beta-estradiol increased PGE2 in one month CL. This study suggests that, in one month CL, PGE2 production could be regulated by progesterone and 17 beta-estradiol, while, in three month CL, this prostaglandin seems to be under the control of progesterone alone. PMID- 7878195 TI - [Morphologic changes of erythrocytes in blood and dysmorphic erythrocyturia]. AB - In chronic glomerulonephritis dysmorphic erythrocytes appear in urine sediment. In the same cases we have found changes in the morphology of erythrocytes of peripheral blood expressed in their size and colouring. In the control group, of non-renal hypertension we didn't notice any dysmorphic erythrocytes in urine as well as any changes in the morphology of erythrocytes in blood. It seems to be possible that there is common mechanism leading to dysmorphic erythrocyturia and to changes in morphology of erythrocytes in peripheral blood in chronic glomerulonephritis. PMID- 7878196 TI - [Surgical treatment of coronary artery disease in the opinion of "first-contact" physicians and their patients]. AB - A group of physicians working at regional dispensaries in Cracow and its surroundings, and their patients were inquired about surgical treatment of coronary artery disease using specially prepared questionnaires. In comparison with a similar study, performed in 1987, a significant improvement of acquirement was stated in both groups. It may be connected with development of coronary surgery during the last years. However, the respondents emphasized a deficiency of easy accessible medical information on this topic. PMID- 7878197 TI - [Hydroxyproline in serum and urine in children with pulmonary hypertension in the course of congenital heart defects]. AB - In accordance to contemporary views on the pathology of biochemical changes in the fibrotic process at pulmonary hypertension, the authors took a trial to investigate the convection of excessive blood flow through lungs and changes of collagen metabolism in lungs. The possibility of following the metabolism of collagen through naming its metabolites (hydroxyproline-Hp) made us to connect the intended surveys with practical trail of its use, and diagnostic methods at children with congenital shunt cardiac defects. The survey was taken up in three groups of children with different levels of pulmonary advancement hypertension process: 39 children with dynamic elevation of pulmonary artery pressure (I st and II nd group age range: 12 months to 2 years), and 17 children with marks of pulmonary vascular obstructive disease. III rd group age range: 12 months to 6 years. It was stated, that between children from the first and second group before operational treatment, clear growth of Hp contents in serum and in urine returned to its correct value within the 1 to 6 months observation period since the cardiac defect has been corrected. In the third group, in spite of surgical treatment, the increased Hp content remained in the post operative period, therefore testifying the non-retreated fibrotic changes. It was stated, that Hp content control in serum and excretion in urine can possess clinical usage as an auxiliary exam estimating the advancement of pulmonary hypertension before surgical treatment and at the post-operative monitoring of the lungs. PMID- 7878198 TI - [Risk factors and surgical tactics in differentiated thyroid cancer]. AB - Differentiated thyroid cancer presents various, frequently astonishing outcomes, not only to the patients but sometimes to physicians as well. The dynamics of progress of the neoplasm is calculating depending on the type of tumor, that is to say microscopic findings, ways of spreading and other prognostic factors, such as: age, sex, grade of histologic malignancy and the advancement of the disease. The authors of this paper try to assess the purposefulness of individual choice of surgical procedure, according to analysis of risk factors (AMES, AGES). Therefore, the surgeon should decide about the extent of the procedure depending on those factors. PMID- 7878199 TI - [Usefulness of imaging methods in the diagnosis of aortic dissecting aneurysms]. AB - Based upon personal experience and literature the authors briefly discuss the usefulness of arteriography, ultrasonography, CT and MR in the diagnosis of aortic dissecting aneurysms. In the diagnostic algorithm concerning aortic dissection type I and II acc. DeBakey, the initial diagnostic method should be echocardiography, followed by CT or MR or eventually aortography. In the case of type III aortic dissection the authors recommend transesophageal echocardiography and CT or MR or eventually aortography as the last examination. PMID- 7878200 TI - [Fungal infection in patients with granulocytopenia. Pathogenetic, diagnostic and therapeutic aspects]. AB - The invasive diagnostic procedures, use of the broad-spectrum antibiotics, adrenal corticoids, immunosuppressive and cytostatic drugs have lead to the increase in the number of fungal infections in granulocytopenic patients. For the most part fungal infections in those patients consist of the opportunistic, systemic infections in granulocytopenic patients is exceptionally frustrating because more often than not, diagnosis is very difficult to establish. The article presents some problems regarding their pathogenesis, classification, diagnosis and management. PMID- 7878201 TI - [A case of Caffey-Silverman's syndrome]. PMID- 7878202 TI - [Notes from a scientific course " How to teach evidence-based medicine"]. PMID- 7878203 TI - [Prof. Jan Glatzel (1888-1954) (40th anniversary of death)]. PMID- 7878204 TI - Radiation-induced apoptosis in a murine lymphoma in vivo. AB - A number of radiobiologic parameters of radiation-induced apoptosis were investigated in a syngeneic murine B-cell lymphoma, designated LY-TH. These included radiation dose effect, kinetics of apoptosis development, the effect of hypoxia and split-dose recovery. Tumors, 8 mm in size, were locally irradiated with graded doses ranging from 1 to 10-Gy gamma rays. Radiation-induced apoptosis was observed as early as 1 h after irradiation, peaked between 4 and 6 h and could no longer be detected 24 h later. The magnitude of the apoptotic response generally increased with radiation dose, but lower doses seemed to be relatively more effective than higher doses. Tumor hypoxia, produced by tumor clamping, inhibited induction of apoptosis by a factor of about 2.5. When two doses of radiation were separated by times of 1-10 days, the proportion of apoptotic cells induced by the second dose was greatly reduced compared to the initial dose. This reduction was the greatest when the second dose was given 2 days after the first dose. The proportion of apoptotic cells induced by the second dose slowly recovered after 2 days but it did not return to the initial levels after as long as 10 days. PMID- 7878205 TI - An equation for the dose response of radiation-induced apoptosis: possible incorporation with the LQ model. AB - Based on in vitro and in vivo data, we proposed an equation to describe the dose response of radiation-induced apoptosis. This equation can be incorporated into the LQ model to account for the contribution of apoptosis-mediated cell death in clonogenic survival curve. The modified LQ equation is a composite of the dose responses of two subpopulations, one susceptible and the other resistant to apoptotic cell death. For the apoptosis-resistant fraction, the size of which varies for different biological systems, the conventional LQ relation applies. For the susceptible subpopulation, the LQ equation is modified by e-zeta D, a functional form consistent with the observed dose-rate independence of this mode of cell death. PMID- 7878206 TI - Synovial sarcoma outcome following conservation surgery and radiotherapy. AB - This retrospective review of 85 patients presents the prognostic factors and disease outcome for localized synovial sarcoma treated with conservation surgery and radiotherapy. Tumors were located in the lower extremity (48), upper extremity (20), trunk (11), and head and neck (6). All patients were treated with limited excision and radiotherapy. Sixty-seven patients had surgery followed by radiation and 18 had preoperative radiation. Postoperative radiation was delivered to a mean dose of 62 Gy, whereas the mean dose for preoperative radiation was 50 Gy. Thirty-five patients, mostly with tumors exceeding 5 cm, received adjuvant adriamycin-based chemotherapy (median adriamycin dose 406 mg/m2). At a median follow-up of 8.4 years the 5-, 10-, and 15-year survival rates were 76%, 63%, and 57%. Mortality was almost entirely due to metastatic relapse. Metastases developed in 36 patients yielding an actuarial 10-year metastatic rate of 48%. In multivariate analysis, tumor size was the dominant determinant of metastases with a lesser contribution due to patient age (those < or = 20 years having fewer metastases). Tumor site and histology were not independently significant. Ten-year metastatic rates according to tumor size, s, were s < or = 2 cm, 0%; 2 < s < or = 5 cm, 35%; 5 < s < or = 10 cm, 59%; 10 cm < s, 100%. Our retrospective data failed to reveal benefits for adjuvant chemotherapy either in univariate or multivariate analysis. Eight patients (9%) had local recurrence as the initial failure and 4 others had local failure after disease appeared elsewhere, yielding a 5-year actuarial local recurrence rate of 14%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878207 TI - Apoptosis and a re-investigation of the biologic basis for cancer therapy. AB - Antitumor therapy has expanded beyond the previous notions of cytotoxic or biologic therapy to now include agents that induce differentiation (e.g. all trans-retinoic acid for induction of complete remission in patients with acute promyelocytic leukemia [23]) or apoptosis [91]. In fact, the phenomenon of apoptosis may be fundamental to the current understanding of carcinogenesis [11] and may also underlie the effectiveness of some forms of chemotherapy [4,5,18,39,56,59,67], radiation therapy [19,44,52,60,64, 77,78,85] and the interferons [73]. The process of apoptosis has been shown to be responsible for the normal elimination of cells with damaged DNA [81] as well as other potentially dangerous cells such as autoreactive T-lymphocytes [14]. Therefore, although much attention has been given to oncogenes that induce cellular proliferation, one can easily see how the same result (i.e. neoplasia) could be obtained when the ability of a cell to undergo apoptosis is lost. PMID- 7878208 TI - Chronic radiation damage in the rat rectum: an analysis of the influences of fractionation, time and volume. AB - PURPOSE: Analysis of four different sets of experiments performed by the G.S.F. group in Munich investigating the late tolerance of the rat rectum to external or intracavitary irradiation. MATERIAL AND METHODS: The endpoint was late rectal stenosis in female Wistar rats. The raw data were fitted to the linear-quadratic model by means of a likelihood maximization method (Direct Analysis). The model was altered to allow for repopulation, incomplete repair, and varying irradiated lengths of the rectum. RESULTS: Fractionation sensitivity was high or intermediate (alpha/beta ratio values [95% confidence limits] ranging from 2.67 [0.86, 4.80] to 6.65 [2.21, 11.73] Gy). Significant repopulation occurred when treatments were longer than 5 days (Dprolif equal to 0.61 [0.20, 1.47] and 1.08 [0.58, 1.90] Gy/day, in fractions of 4 Gy). Another interpretation is that radiosensitivity changed during treatment. Repair half-time estimates ranged between 1.84 [1.52, 2.34] and 5.02 [2.83, 21.7] h. Finally, the present analysis indicated that the smallest surviving compartment capable of tissue rescue was about 1/50 to 1/100 of a 1 cm high cylinder of the rectum wall. CONCLUSIONS: The radiobiological features of late stenosis in the rats are consistent with combined injuries of early and late responding components of the rectal wall. This raises some concerns about the possible danger of hyperfractionated treatments, where the beneficial impact of fraction size reduction may be obviated for interfraction intervals that are too short. Also, accelerated irradiation may result in more late complications because of increased early reactions. PMID- 7878209 TI - Use of a CT simulator in radiotherapy treatment planning for breast conserving therapy. AB - A CT simulator (CT-S) is a real-time, CT-linked, 3-D treatment planning system, which consists of a CT scanner, a multi-image display, a treatment planning device with real-time visual optimization, and a laser beam projector. This system was clinically evaluated in 339 Stage 0, I and II breast cancers in 337 patients who received breast conserving therapy. Following quadrantectomy or wide excision with complete axillary dissection, a total of 50 Gy was delivered to the ipsilateral breast using 60Co gamma-rays. In patients with involved surgical margins, boost electron irradiation was also given. Treatment planning could be accomplished within 40-50 min using the CT-S. The parameters for the tangential portals could be optimized for each patient, and the wedge filters and the electron energy for boost irradiation could be appropriately selected. The incidence of moist desquamation and depigmentation at the areola was slightly decreased with the use of wedge filters. During the follow-up for 2-71 months (median, 22 months), local recurrence and symptomatic radiation pneumonitis occurred in one patient each. The CT-S appears to be useful for the individualized optimization of tangential irradiation fields in breast conserving therapy. PMID- 7878210 TI - Influence of the positioning error on 3D conformal dose distributions during fractionated radiotherapy. AB - The influence of patient immobilization error on 3D planned conformal radiation therapy in tumors of the thorax and pelvis was studied. The mean positioning error in 43 patients with carcinomas of the thorax and pelvis undergoing 3D conformal radiotherapy (laser supported alignment, no immobilization device) was measured. A total of 194 portal films were superposed with the corresponding simulator radiographs according to anatomic landmarks and using a subtrascope. x , y- and z-axis deviation was determined within a coordinate system. Using specialized software including Fourier transformation the mean positioning error was employed to recalculate the dose distributions of all cases under the influence of random (Gaussian) immobilization uncertainty. The mean two dimensional positioning error using the data from all patients was 5.5 (+/- 3.7) mm. The distribution was Gaussian. Dose volume histograms (DVHs) of each patient with and without consideration of positioning uncertainty were compared on the base of tumor control probability estimations (TCP) using published DVH reduction and TCP algorithms. Inclusion of the positioning error resulted in a mean decrease in TCP (given as the difference between the TCP assuming no positioning error and the TCP modified by the positioning error) of 2% in a series of esophagus carcinomas and of 5% in the prostate carcinomas when looking at gross tumor volume (GTV), only. Planning target volume (PTV) exhibited a relative decrease in TCP of 5% and 11%, respectively. PMID- 7878211 TI - Head-scatter factors in blocked photon fields. AB - The behavior of the head-scatter factor in shielded 6 and 25 MV X-ray beams from a Philips SL25 linear accelerator was investigated by measuring incident fluences by direct (in-air) and indirect (in-phantom) methods. It was found that perturbations in head-scatter produced by shielding blocks arranged to define a slit-shaped field are considerably less than 1% in unwedged beams, even when 80% of a 20 x 20 cm2 field is shielded. The results are independent of beam energy and orientation of the slit with respect to the collimator jaws. When a 60 degrees wedge is inserted, the head-scatter factor decreases by up to a few percent, depending on slit direction but not on energy. The contributions to head scatter from the block tray and the shielding blocks are negligible. PMID- 7878212 TI - Patient positioning for fractionated precision radiation treatment of targets in the head using fiducial markers. AB - When irradiating targets in the brain, an accurately localised dose is often needed. One crucial moment to achieve this is the positioning of the patient. We have developed a positioning method where the patient is immobilised with a bite block and a head mould, and where the position of the target is determined by X ray imaging of fiducial markers that are placed in the patient's skull. A method for computing the transformation needed to move the target from the observed to the prescribed position and orientation is described. This method uses the information from two orthogonal X-ray images and takes measurement errors and data from three or more markers into account. Results from using the method clinically in proton beam therapy are given. PMID- 7878213 TI - Improved target volume definition for precision radiotherapy planning of meningiomas by correlation of CT and dynamic, Gd-DTPA-enhanced FLASH MR imaging. AB - In this methodological paper the authors report a fast, T1-weighted gradient-echo sequence (FLASH) for dynamic, Gd-DTPA-enhanced magnetic resonance (MR) imaging of meningiomas and its application in precision radiotherapy planning. Indications for radiotherapy included unresected tumors, tumor remaining after surgery, and recurrences. The patient's head was fixed in a stereotactic localization system which is usable at the CT, MR and the linear accelerator installations. By phantom measurements different materials (steel, aluminum, titanium, plastic, wood, ceramics) used for the stereotactic system were tested for mechanical stability and geometric MR image distortion. All metallic stereotactic rings (closed rings made of massive metal) led to a more or less dramatic geometric distortion and signal cancellation in the MR images. The best properties--nearly no distortion and high mechanic stability--are provided by a ceramic ring. If necessary, the remaining geometric MR image distortion can be 'corrected' (reducing displacements to the size of a pixel) by calculations based on modeling the distortion as a fourth order two-dimensional polynomial. The target volume was defined in dynamic, T1-weighted FLASH MR images, which were measured before, during, and after the controlled intravenous infusion of 0.1 mmol/kg body weight Gd-DTPA. The stereotactic localization technique allows the precise transfer of the target volume information from MR onto CT data to provide a map of the radiation attenuation coefficient for dose calculation. In genera, the superior soft tissue contrast of MR showed an excellent tumor delineation, especially in regions, such as the base of the skull, where the target often was obscured in CT images.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878214 TI - Design of a non-docking intraoperative electron beam applicator system. AB - A development of a non-docking system is described which enables collimation of an electron beam for intraoperative radiation therapy. This system, adapted to a linear accelerator (SATURNE 43-CGR MeV), has been designed to minimize the mechanical, electrical and tumor visualization problems associated with a docking system. A number of dosimetric considerations and technical innovations have been used in the design of this system. Among them are the central axis of the beam alignment with the axis of the cone via a laser system and the clamping method of the intraoperative cone to the treatment couch by a rigid system. This collimation system can be adapted for different makes of linear accelerator. The dose distribution in this new design system shows a better homogeneity in the patient's target volume and small (thus accessable) leakage radiation dose to tissues outside the intraoperative cone. The design concept and dosimetric characteristics of this novel applicator system are presented in this paper. PMID- 7878215 TI - A feasibility study of partially accelerated radiotherapy for invasive bladder cancer. AB - Thirty-nine patients with histologically confirmed invasive bladder carcinoma (T2 3, N0, M0) were treated with a partially accelerated radiotherapy scheme. After 40 Gy/4 weeks of conventional fractionation we have accelerated the treatment in the last week giving two daily fractions of 2 Gy each, 4-6 h apart in the bladder only. Although the follow-up of some of the patients is not very long our results indicate that this relatively short radiotherapeutic scheme is feasible, convenient and probably safe for patients living in remote areas. PMID- 7878216 TI - Combined single course carboplatin with radiotherapy in treatment of stage IIA,B seminoma--a preliminary report. AB - Twenty-one patients with Stage IIA or B seminoma have been treated post orchidectomy by a single course of carboplatin prior to conventional radiotherapy in either the Royal Marsden Hospital or the Norwegian Radium Hospital during 1989 1993. Follow-up ranged from 8 months to 51 months with a mean of 36 months and median 34 months. All patients achieved complete remission and remain disease free. The main side-effects were nausea and vomiting while haematological toxicity was slight. There was no symptomatic peripheral neuropathy, ototoxicity or deterioration of renal function. This combined modality approach is rational, feasible, and effective, although a larger number of patients with longer term follow-up are needed for reasonable comparison with the use of infradiaphragmatic radiotherapy alone. PMID- 7878217 TI - Chronic radiation damage in the rat rectum: an analysis of the influences of fractionation, time and volume. PMID- 7878218 TI - Comparative structure and function of marsupial spermatozoa. AB - Marsupial sperm structure has been the focus of many comparative studies in the last 30 years. Although the basic organization of the marsupial spermatozoon is similar to that of eutherian mammals, spermatozoa from this branch of therian evolution have developed a specific suite of characters which clearly distinguish them from the Eutheria. This review surveys these specializations and examines current knowledge on their respective functions and the forces which shaped their evolution. Nuclear shaping and stability, the asymmetric positioning of the acrosome, and the unusual neck articulation are discussed. Although recent observations have provided evidence of a marsupial equatorial segment and posterior ring, the marsupial equivalent of the eutherian postacrosomal sheath has not been identified. The unusual neck structure of marsupial spermatozoa and the mobile articulation of the connecting piece are discussed in relation to nuclear rotation and the events associated with this process. Increasing flagellar length in some species is associated with extremes in flagellar organization and its effect on sperm motility is discussed. PMID- 7878219 TI - Interactions of sperm and the reproductive ducts of the male tammar wallaby, Macropus eugenii (Macropodidae: Marsupialia). AB - This review compares sperm production in the tammar wallaby and eutherian mammals, particularly the rat. The capacity of sperm to fertilize an ovum when they leave the testis and the changes they undergo in the epididymidis are considered. The structural differentiation and regulation of the extratesticular duct system is assessed and related to the reabsorption and secretion of water, inorganic ions and proteins, and the interaction of sperm and proteins synthesized and secreted by the epididymidis. Adaptations of the cauda epididymidis for storing spermatozoa are also considered. It is suggested that the tammar may be a good animal model to study the suppression of sperm motility and metabolism in the cauda epididymidis as it is possible to collect from them luminal samples of sperm which are initially immotile and then spontaneously activate during incubation in vitro. PMID- 7878220 TI - Male-induced oestrus and ovulation in female brush-tailed bettongs (Bettongia penicillata) suckling a young in the pouch. AB - Female brush-tailed bettongs isolated from males usually do not come into oestrus or ovulate. Individuals isolated during pregnancy and at parturition do not ovulate post partum and are in the unusual condition for a macropodoid of suckling a pouch young but lacking a quiescent corpus luteum or a diapause embryo. Females in this condition were tested for their ability to come into oestrus and to ovulate after re-introduction to the male. When returned to the male on Day 1 of lactation, females generally mated before Day 2 and ovulated; at all later stages of lactation, six or seven days after being returned to the male > or = 50% of females came into oestrus, mated and ovulated. The vaginal smears of most females in isolation were typical of post oestrus on Day 2; after being returned to the male on Day 11, these females came into oestrus in seven days, mated and ovulated. The results show that suckling a young in the pouch does not suppress ovulation in this species provided that an adult male is present. Moreover, the results indicate that the mechanism of male-induced ovulation 24 h post partum differs from that of the remainder of the pouch suckling period. PMID- 7878221 TI - A comparison of sperm and embryo transport in the female reproductive tract of marsupial and eutherian mammals. AB - A review on current knowledge of sperm and embryo transport in the female reproductive tract of marsupials. Some of the unique features of gamete structure function and female genital tract morphology will be described and compared with data available on eutherian mammals. PMID- 7878222 TI - Prefertilization gamete maturation events in marsupials. AB - Despite many fundamental similarities between the gametes of marsupials and placental mammals, the regulation and timing of prefertilization gamete maturation are quite different. The marsupial acrosome is remarkably stable and an acrosome reaction (AR) is not induced by reagent effective for the sperm of placental mammals. The ultrastructure of the marsupial sperm AR is essentially similar to that of placental mammals, however, whether an equatorial segment (ES) persists to serve as the site of sperm-egg membrane fusion is unclear. Diacylglycerol induction of the AR suggests that the sperm of Australian species lack an ES, yet an ES-like region appears to be involved in fertilization in the opossum Monodelphis. The marsupial oocyte, unlike those of placentals, continues to grow throughout follicular life and major cytoplasmic maturation events occur late in oocyte development. Cortical granules only become evident shortly before ovulation and mature dark granules may only appear after ovulation. Further, the zona pellucida (ZP) changes in character and function during the peri-ovulatory period. In vitro fertilization has been achieved for an opossum but not for any Australian marsupial, owing to failure of sperm-ZP binding. Requirement for a sperm maturation process is likely, but capacitation treatments used for placental sperm in vitro have been ineffective. Since it is now feasible to experimentally manipulate marsupial gametes in vitro major advances in our understanding of their function can be expected. PMID- 7878223 TI - How does sperm meet egg?--in a marsupial. AB - Australian marsupials exhibit a wide range of variation in sperm head morphology, and in thickness of the zona pellucida around the oocyte, suggesting interspecfic differences in the processes of sperm-egg interaction. The observations described here are largely based on the dasyurid Sminthopsis crassicaudata. They show that in oestrous females, after mating, a coagulum forms in the lateral vaginae and, within an hour of insemination, numerous spermatozoa congregate in the isthmus of the oviduct in which the vanguard population undergoes transformation with the head rotating on its axis with the tail to form a T-shape. Once oocytes are released, a few spermatozoa migrate to the higher reaches of the oviduct where sperm-zona binding occurs by way of the plasmalemma over the acrosomal region. The acrosome reaction takes place here and, as the egg rotates, the tail of the spermatozoon becomes parallel to the head. A small region of acrosome sometimes appears to remain intact at this time because spermatozoa with partly intact acrosomes have been found within the zona matrix. In some of these, electron dense bridges between part of the inner and outer acrosomal membranes which may act as stabilizing structures, were also seen. The zona matrix is tightly packed around the penetrating spermatozoon, but that close to the acrosomal region becomes less electron-dense and more filamentous. Once incorporated into the egg, the spermatozoon lacks a cell membrane around the tail but vesicles close to the sperm head may, at least in part, be remnants of an inner acrosomal membrane. How generally applicable these observations are to other Australian marsupials remains to be determined. PMID- 7878224 TI - Development of early cell lineages in marsupial embryos: an overview. AB - All major embryonic and extra-embryonic cell lineages are established before implantation in marsupials. In reptiles, birds, monotremes and most marsupials, the zygote is polarized, sometimes markedly so, and the cleavage pattern in relation to the polarized state provides the mechanism for the generation of positional signals. These ensure that the embryonic cell lineages develop in the centre of the developing blastoderm or blastocyst epithelium and the extra embryonic lineages at the periphery. The evolution of the vertebrate yolky egg was accompanied by a decreasing dependence on maternal determinants and increasing dependence on positional signals to determine cell fate. It is proposed that when a less yolky egg evolved, the mechanisms for determination of cell fate in a developing epithelium were retained. It is proposed that in marsupials, positional signals are involved in the determination of cell fate of embryonic and trophectoderm cells but do so in a two-dimensional epithelium not a three-dimensional morula. The next lineage formed is the primary endoderm which separates off from the primitive ectoderm in the embryoblast and eventually lines the blastocyst cavity. Positional signals are responsible for the determination of primary endoderm in eutherian mammals, birds and probably also marsupials. Order of cell division during cleavage provides a mechanism whereby some cells in the embryoblast of marsupials have earlier and greater contact with their neighbouring cells. The mechanism for determination of primary endoderm cells in the blastocyst epithelium is examined in the Virginia opossum and the stripe faced dunnart. PMID- 7878225 TI - HPRT activity in embryos of a South American opossum Monodelphis domestica. AB - Marsupial females show preferential paternal X-inactivation. However, the time at which X-inactivation occurs in early development has not yet been determined. A double microassay which measures the activities of X-linked hypoxanthine phosphoribosyl transferase (HPRT) and the autosomally-coded adenine phosphoribosyl transferase (APRT) from the same sample was performed on a collection of embryos from a South American opossum Monodelphis domestica. The embryos ranged in age from the 2-cell stage to the bilaminar blastocyst stage. The results indicate that their embryonic HPRT and APRT are not expressed until just before the unilaminar blastocyst stage in M. domestica. This is at a later stage of development than that in the mouse where embryonic HPRT and APRT expression first occurs at the 4-8-cell stage. It is concluded that HPRT is an uniformative enzyme for assessing X chromosome activity in cleaving embryos of M. domestica. The widespread distribution of HPRT:APRT ratios after the unilaminar blastocyst stage also makes it difficult to draw conclusions about the state of X chromosome activity in early marsupial development. PMID- 7878226 TI - X-chromosome replication patterns in adult, newborn and prenatal opossums. AB - Somatic cells from the opossums Monodelphis domestica and Didelphis virginiana were labelled with 5-bromodeoxyuridine (BrdU), treated with colchicine, stained with acridine orange and examined using fluorescence microscopy. BrdU incorporated metaphase spreads from females of M. domestica at developmental stages from late bilaminar blastocysts to adults showed replication asynchrony of the two (acrocentric) X chromosomes. The long arm of one X chromosome was the latest replicating region in the entire chromosome complement and is presumed to represent transcriptional inactivation and X dosage compensation. The minute short arm of the same X, which contains a nucleolar organizer region, was earlier replicating and synchronous with the short arm of its homologue and is thus assumed to escape inactivation. BrdU-incorporated spreads from cells of fetuses, neonates and adults of D. virginiana also showed a late replicating (submetacentric) X chromosome. The pattern was different from that of M. domestica because of the different morphology and the presence of large blocks of constitutive heterochromatin in both homologues. The timing and pattern of replication of the single X in males of both species resembled the earlier replicating X in females. The array of molecular techniques now available offers the best means for investigating X-chromosome replication and activity states of X-linked genes in the earliest stages of marsupial embryogenesis. PMID- 7878227 TI - [Modern imaging of maxillofacial deformities]. AB - Facial malformations make a wide chapter of maxillofacial abnormalities whose treatment needs an accurate clinical-instrumental analysis to quantify malformation entity and to agree on precise lesion classification and subsequent management. Maxillofacial abnormalities are classified as congenital, growth related and acquired. Congenital deformities include the alterations present at birth, i.e., craniofacial stenosis, oto-mandibular syndrome. Treacher-Collins and Goldenhar syndrome, facial clefts and lip-palate clefts. Growth-related malformations include the deformities appearing during growth and which are called maxillary dysmorphosis, e.g., hemimandibular hyperplasia, prognathism, maxillary hypoplasia, etc. Acquired malformations are those remaining after trauma or cancer surgery and those which are secondary to fibrous dysplasias of the craniofacial complex. May 1990 through May 1993, forty-two patients with different malformations were examined. The malformations secondary to cancer surgery were not included in our series. A radiologic study including conventional skull radiography, teleradiography and panoramic tomography had been performed for preliminary assessment before axial CT studies and 2D and 3D reconstructions. As for our series, in 20 patients coventional radiology was exhaustive to diagnose the disorder and to supply essential elements for treatment planning while axial CT and 3D reconstructions added no further piece of information. Only in the most complex malformations and in all cases of congenital malformations was axial CT needed to assess the type, extent and entity of the malformations allowing both the diagnosis and adequate surgical planning. PMID- 7878228 TI - [Lesions of the rotatory cuff: diagnostic validity of echography. Surgical findings]. AB - Ultrasonography is the method of choice in the study of rotator cuff tears, a very frequent event especially as the final outcome of the impingement syndrome. The authors investigated US sensitivity with the retrospective review of 20 surgical patients with a chronically painful shoulder. US sensitivity was 85%, with 15% false-negative results. Seventeen true-positive cases were restudied for the three main US signs of cuff tear: marked tendon thinning was observed in 64.7% of cases, cuff disappearance in 23.5% and focal discontinuity in 11.8%. This retrospective study confirms that, whenever US shows a cuff tear, the diagnosis can be made, while when US findings are negative or questionable, but clinics are positive, MRI must be performed. PMID- 7878229 TI - [Static-dynamic computerized tomography in the diagnosis of traumatic lesions of alar ligaments. Preliminary results]. AB - The patients affected with cervical injuries often complain of cervical pain, headache and dizziness even when no bone fractures are detected. Such patients are likely to have a post-traumatic injury of the cervical ligaments. Twenty-five symptomatic patients (19 women and 6 men) were examined with upper spine CT and functional CT scans (right and left rotation) to detect ligament injuries and hypermotility of the craniocervical junction, both related to traumatic events. Eleven patients showed no alterations, while unilateral densitometric alterations of the alar ligaments were observed in 14 cases and thought to be related to trauma. On axial CT scans, the normal alar ligaments were identified as paramedian, quadrangular soft-tissue structures at the apex of the dens epistrophei and right above it. In 14 patients with alar ligament injuries, CT showed incomplete ligament interruption and thinning in 12 cases and its total absence on all images in 2 cases. The laterodental space in the affected side was hypodense due to fat tissue replacement. Of 14 patients with alar ligament injuries, only 14 patients with alar ligament injuries, only 4 exhibited rotatory hypermotility at C0-C1 and C1-C2. The low frequency of rotatory hypermotility is probably due to the high rate of incomplete alar ligament injuries as well as to cervical muscle stiffness, which is marked in some subjects. In conclusion, static and functional CT of the upper spine is not only useful to predict trauma outcome, but also allows the detection of the alar ligaments, of their morphodensitometric changes and of the segmental instability of the craniocervical junction. PMID- 7878230 TI - [Comparison of echography and magnetic resonance in sprains of the external compartment of the ankle]. AB - In most cases ankle sprains involve external compartment ligaments. In particular, the anterior talofibular ligament is involved alone in 70% of cases and together with calcaneofibular and posterior talofibular ligaments in the remaining 30% of cases. To investigate the potentials and the possible limitations of high-frequency US (7.5-13 MHz) for the preliminary assessment of the extent of damage of the capsulo-ligamentous lesions of the external ankle compartment, 25 athletes with clinical diagnosis of sprain trauma were examined with conventional radiology. Morphology and structure were studied from the semiologic point of view. US findings were compared with MR results. In all patients, US showed anterior talofibular ligament lesions alone in 13 patients and associated with calcaneofibular ligament lesions in 12 patients. The posterior talofibular and the interosseous talocalcaneal ligaments were never demonstrated by US. In 4/13 patients diagnosed by US as having isolated anterior talofibular lesions, MRI demonstrated a coexisting calcaneofibular lesion (4/13) and, in one of them, a posterior talofibular and interosseous talocalcaneal ligaments lesion. The comparison of US and MR findings in the patients US had diagnosed as having associated anterior talofibular and calcaneofibular ligaments lesions, showed 100% agreement; MRI allowed the demonstration of the lesions in the posterior talofibular and interosseous talocalcaneal ligaments in 2/12 patients. Considering the statistical prevalence of the anterior peroneal astragalic lesions caused by ankle sprains, the use of high-frequency US as the first diagnostic approach seems justified. Nevertheless, MRI is a fundamental complement for accurately assessing damage extent. PMID- 7878231 TI - [Multiple sclerosis with negative cerebrospinal fluid. Magnetic resonance differential diagnosis]. AB - This study was aimed at investigating the value of MRI in the diagnosis of multiple sclerosis. In the Multiple Sclerosis Center of our University, we sorted out of the patients submitted to CSF and MR examinations, only those with clinically unquestionable multiple sclerosis, white matter abnormalities at MRI and normal CSF examination. These 21 patients were submitted to CSF and MRI examinations which were repeated whenever required if image quality was technically suboptimal; a variety of screening tests for different diseases mimicking multiple sclerosis were also performed. In 4 patients with white matter abnormalities at MRI which were considered atypical for multiple sclerosis, at image rereading and after laboratory tests the diagnosis were: coagulopathy, sarcoidosis, vasculitis and CNS lymphoma. In 2 cases with questionable white matter abnormalities at MRI, the final diagnosis were borreliosis and vasculitis. The remaining 15 patients had a diagnosis of multiple sclerosis in all but 3 cases in which subsequent clinical and laboratory examinations demonstrated the presence of vasculitis, embolism from interatrial septal aneurysm and mitochondrial disease. Our study suggests that in the patients with clinical findings of multiple sclerosis and disseminated MR lesions mimicking multiple sclerosis, but no CSF abnormalities, the classical clinical criteria may not be sufficiently specific and other diagnoses must therefore be excluded before making an "unquestionable" diagnosis of multiple sclerosis. PMID- 7878232 TI - [Cerebral magnetic resonance in Wilson's disease]. AB - The authors describe the typical and atypical MR findings of brain abnormalities in Wilson's disease in three patients affected with severe neurologic disturbances; a low-field MR unit was used. Radiologic findings included atrophic changes and focal lesions. Two patients had basal ganglia, brain stem and dentate alterations; lesions in the corpus callosum (a site not yet described in Wilson's disease) were seen. The third case had putaminal lesions which improved after penicillamine therapy. Cerebral abnormalities were demonstrated as areas of increased signal on T2-weighted images; T1 and T2 shortening due to magnetic susceptibility phenomena was not seen. Two major MR features were observed: high hyperintensity and peripheral location of putaminal lesions and sparing of the medial thalami in diffuse basal ganglia involvement. PMID- 7878233 TI - [Use of computerized tomography in asthmatic patients]. AB - This study was aimed at assessing the role of high resolution Computed Tomography (HRCT) in the asthmatic patient, during disease worsening. Chest radiography plays a major role in the assessment of the most common complications of asthma, such as pneumothorax, pneumomediastinum, or lobar collapse. Conventional CT and HRCT are sometimes used when a complication is suspected, particularly chronic eosinophilic pneumonia and allergic bronchopulmonary aspergillosis. We prospectively examined 31 asthmatic patients with clinical and functional worsening submitting them to chest radiographs and HRCT scans. In 5 of them, radiographic findings were suggestive of a complication: 3 patients presented allergic bronchopulmonary aspergillosis and 2 chronic eosinophilic pneumonia; in these cases HRCT confirmed the diagnosis and yielded other useful pieces of information, but did not change the prognosis or the therapeutic approach. In the remaining 26 patients, HRCT findings were abnormal in 61% of cases, while chest films were abnormal in 26% of cases only. An outstanding diagnostic contribution came from HRCT which demonstrated a high incidence of small airway disease and, above all, cylindrical bronchiectasis (53.8%), especially in the upper lobes. HRCT also demonstrated that asthma does not usually cause emphysematous destruction in the patients that never smoked. Even though our study enrolled only a small number of patients, the results suggest that asthma is a more destructive disease than previously believed and that HRCT could be a useful examination to perform even when chest film findings are normal. PMID- 7878234 TI - [Artifacts in magnetic resonance angiography]. AB - This study was aimed at assessing and classifying the incidence of Magnetic Resonance Angiography (MRA) artifacts using the 2D and 3D time-of-flight (TOF) technique. MATERIALS AND METHODS: from 300 MRA examinations performed January 1991 through April 1993, we selected the first 10 examinations for each vascular region which exhibited an artifact. Many kinds of artifacts were considered, i.e., hardware, sequence, magnetic susceptibility, patient and maximum intensity projection (MIP) artifacts. A superconductive 1.5-T magnet (Magnetom, Siemens) was used, with 2D and 3D TOF acquisitions. RESULTS: the quantitative analysis of artifact frequency showed that in the intracranial vessels (2D and 3D TOF sequences) the most common artifacts are saturation (30%) and magnetic susceptibility (30%) artifacts. As for neck vessels (3D TOF sequences), turbulence (40%) and lack of inclusion (30%) artifacts are the most common ones. In thoracic vessels (2D TOF sequences), MIP (50%) and ghost (30%) artifacts are the most common ones, while in the abdominal aorta (2D TOF sequences) magnetic susceptibility (20%), voluntary movement (20%), peristalsis (20%) and MIP (20%) artifacts occurred most frequently. Saturation (30%) and respiratory movement (30%) artifacts were the most common ones in the study of the renal arteries (3D TOF sequences), while MIP artifacts prevailed (40%) in the inferior vena cava (2D TOF sequences). Finally, MIP (40%) and patient movement (30%) artifacts were the most frequent ones in the study of the lower limbs (2 TOF sequences). CONCLUSIONS: in 2D and 3D TOF studies, being familiar with artifacts and their physical principles helps avoid image misinterpretation so that, if no technical means can prevent an artifact from occurring, at least it will not become a diagnostic pitfall. PMID- 7878235 TI - [Magnetic resonance in postoperative evaluation of aortic dissection]. AB - The value of MRI was investigated in the demonstration of residual alterations and postoperative complications of aortic dissection. October 1988 to December 1992, fifty-nine patients were examined with MRI. The series consisted of 53 patients affected with type A and 6 with type B aortic dissection, all of them surgically treated. The following parameters were studied: 1) aortic dilatation above and 2) below the prosthesis, 3) redissection, 4) persistent intimal flap, 5) origin of abdominal vessels from the false lumen and 6) study of supra-aortic vessels. Twelve of 59 patients were considered normal since all parameters were negative. The aorta was dilated in 19 patients distal to the graft and in 4 proximal to it. Redissection was observed in 33 of 59 patients. Residual intimal flap was clearly demonstrated in 33 of 59 patients; the state of the false lumen was clearly depicted in 12 patients with SE images alone and in 18 of the extant 21 with phase imaging. In 11 of 59 patients abdominal vessels originated from the false lumen. In 53 of 59 patients supra-aortic vessels were clearly demonstrated and appeared to be involved in 10 patients. In 6 cases MRI failed to yield enough information. In our experience MRI is the method of choice for monitoring the aorta after surgical dissection to detect changes and complications and therefore choose the most appropriate treatment. PMID- 7878236 TI - [Ultrasonographic findings and integration with computerized tomography in pathology of the abdominal wall]. AB - Ultrasonography (US) plays a major role in the study of the anterior and lateral abdominal wall. Our experience refers to 150 patients examined over a 5-year period, who were divided into two groups according to disease etiology: 72 patients suffered from iatrogenic and 78 from non-iatrogenic conditions. The first group was mainly composed of alterations caused by anticoagulation therapy, e.g., hematomas, and recent or previous surgery, i.e., 19 incisional hernias and 19 inflammatory-abscess processes. The second group included above all 32 cases of abdominal wall hernia, 18 neoplasms, 13 traumas with abdominal wall involvement only and 12 inflammatory processes. US yielded valuable pieces of information to diagnose iatrogenic conditions, even for small or non-relevant conditions. Moreover, US allowed non-iatrogenic conditions to be located and identified, accurately demonstrating abdominal wall layers involvement. US was also very useful in the patients whose physical examination is of no use or difficult, e.g., in the patients with much pain and trauma or obese patients. CT was used in selected cases only, as a complement to US, when a more detailed spatial assessment of wide or deep lesions was necessary. PMID- 7878237 TI - [Computerized tomography in gaseous hypotonic duodenography in the study of the pancreatico-duodenal area]. AB - This study was aimed at assessing the role of CT-hypotonic gaseous duodenography in the study of the pancreatic-duodenal region. Forty-two patients with malignancies in this region were examined with CT of the upper abdomen followed by CT-hypotonic gaseous duodenography (30 pancreatic head cancers, 7 main bile duct and 5 ampullary lesions). In 20 of 28 cases of pancreatic head carcinoma, CT hypotonic gaseous duodenography yielded more pieces of information than baseline abdominal CT and was also more useful in small pancreatic head cancers, < 4 cm diameter. In 4 of these patients, CT-hypotonic gaseous duodenography better demonstrated the pancreatic lesions which conventional CT had demonstrated poorly. In contrast, CT-hypotonic gaseous duodenography was less useful in main bile duct carcinomas, depicting focal duodenal infiltration in only 1 of 7 cases. In all ampullary tumor patients (5/5), CT-hypotonic gaseous duodenography demonstrated intraduodenal lesions. The authors conclude that CT-hypotonic gaseous duodenography is a useful technique to investigate small pancreatic head cancers and the method of choice to demonstrate ampullary lesions. PMID- 7878238 TI - [Percutaneous gastrostomy. Personal experience in 137 cases]. AB - Percutaneous gastrostomy is reported to be an effective alternative to total parenteral feeding or long-term nasogastric tube in the treatment of mechanical or functional dysphagia. The authors report their personal experience with 137 percutaneous gastrostomies performed on 98 men and 39 women from January 1986 through December 1993. All the maneuvers were performed under fluoroscopic guidance in the patients with head or neck cancer, neoplastic, vascular or post traumatic neuropathy and upper GI tract cancer. To avoid left hepatic lobe trauma, percutaneous gastrostomy needs to be performed under US guidance. A 7F nasogastric tube is used to fill the stomach with air. After distending the gastric cavity, with the Seldinger technique under local anesthesia, fascial dilators of progressively increasing caliber are introduced into the gastric cavity and the final 12F gastrostomy catheter is positioned under fluoroscopic guidance. No major complications, such as hemorrhage or peritonitis, occurred. In one case, during the maneuver, the patient complained of severe epigastric pain which regressed with no further problems two hours later. In three cases the gastrostomy catheter fell out of place and was replaced by running the fistolous tract with a venous cannula and then a guidewire for gastrostomy repositioning. With this type of treatment, the patient can be given enteral feeding the following day. The maneuver requires approximately 10 minutes to perform and is well tolerated by the patient as it requires no general anesthesia. Percutaneous gastrostomy is more cost-effective than surgery or endoscopy and hospitalization is shorter. The only contraindications to this maneuver are hepatomegaly (because of the risk of liver trauma during percutaneous maneuvers), ascites (because of the risk of infection) and finally the complications resulting from gastric resection. PMID- 7878239 TI - [Kohlrausch's plica (plica transversalis recti): localization, morphology, function]. AB - The plica transversalis recti (K Kohlrausch's plica or Houston's valve) shows a preferential double (52%) rather than triple (38%) localization and is absent in as much as 16% of cases. It is alternatively found on the left and right sides, 3 4 and 8-9 cm from the anal margin respectively. Both its detection rate and radiographic features depend on the technique used as follows: (a) 92%, contour indentation and/or linear filling defect, 4 to 5 mm thick at barium enema studies; (b) 67%, the same as in (a) plus 1/3 narrowing of the maximum diameter at defecography; and (c) 90%, two opposite and overlapping folds at coronal CT. Evidence is given that neither organic nor functional anorectal conditions affect the radiographic appearance of the fold, its likely role being to fix the proximal margins during the expulsion of feces. PMID- 7878240 TI - [Digital angiography and lipiodol computerized tomography in the anatomopathological framework of hepatocarcinoma]. AB - The introduction of therapies other than conventional surgery of hepatocellular carcinoma (HCC) requires an accurate pathologic classification, which is important because it is well known that HCC may have multicentric growth. The Liver Cancer Study Group of Japan has proposed a classification dividing HCCs into three macroscopic forms from the pathologic point of view: nodular, massive and infiltrating HCCs. The nodular type is subdivided into four types: single nodular type, single nodular type with surrounding proliferation, multinodular fused type and multinodular type. Forty-six HCC patients were examined with Lipiodol Computed Tomography (LCT) to investigate the agreement between pathologic and imaging findings. LCT proved to be in close agreement with pathologic findings. Sixteen cases were classified as type I (single nodular type), 8 as type II (single nodular type with limited foci), 1 as type III (multinodular fused type), 18 as type IV (multiple nodular type with diffuse foci) and 3 cases as type V (massive form). No cases of infiltrative forms were observed in our series. Based on LCT findings, the capabilities of digital subtraction angiography (DSA) were studied in the pathologic classification of HCCs. DSA exhibited some limitations in the pathologic classification of HCCs in 5 of 16 patients with type I lesions. In these cases DSA suggested false-positive diagnoses because of regenerative nodules in cirrhotic liver in 3 cases and of daughter nodules (not confirmed at LCT) in 2 cases. In 7 of 8 patients with type II HCCs, DSA failed to show the daughter nodules surrounding the main nodule. In the 18 patients with multiple distant nodules (type IV), DSA was less sensitive in defining nodule number and site. In the massive form, the information obtained with LCT and DSA was comparable. In conclusion, LCT should be considered a basic examination in the study of HCC extent. Based on LCT findings, the most appropriate treatment can be selected, be it surgery, alcohol injection, or intraarterial chemoembolization. PMID- 7878241 TI - [Role of magnetic resonance in the follow-up o hepatocarcinoma treated with percutaneous ethanol injection (PEI) or transarterial chemoembolization (TACE)]. AB - The purpose of this study was to assess Magnetic Resonance Imaging (MRI) patterns of hepatocellular carcinoma (HCC) treated with percutaneous ethanol injection (PEI) or Transarterial Chemoembolization (TACE) and, consequently, the potential role of MR Imaging in the follow-up of these lesions. HCC treated with PEI. Thirty-one patients with a single small HCC lesion underwent MR Imaging at 0.5 T before and after PEI. In all cases before and after treatment contrast enhanced Computed Tomography (CT) and US-guided fine-needle biopsy were performed. Twenty seven of 31 HCC lesions in which complete tumor necrosis was obtained with PEI showed homogeneous hypointensity on SE T2-weighted MR images. This feature corresponded to an unenhanced and low-attenuation area on follow-up contrast enhanced CT scans. All these lesions were negative for malignant cells at fine needle biopsy follow-up. In four HCCs, high-signal areas on SE T2-weighted images and high-attenuation areas on contrast-enhanced CT scans were observed, suggesting the presence of residual tumor tissue; these lesions were positive for malignant cells at 6-month fine-needle biopsy. In each case, incomplete tumor necrosis was confirmed at pathologic examination of the surgical specimen. HCC treated with TACE. Twenty-one patients with a total of 36 HCC lesions underwent plain and Gadolinium-enhanced MR Imaging before and after TACE. 10 HCC lesions were later surgically resected; 26/36 lesions underwent MR, CT and angiographic follow-up. At short-term follow-up exams (15-30 days), hypointensity was present on enhanced SE T1 weighted sequences in those lesions (5/10) in which complete tumor necrosis was histologically confirmed. In the remaining 5/10 HCC lesions, persistent viable tumor portions were found at pathology. These areas corresponded to areas on hyperintensity of Gadolinium-enhanced SE T1-weighted images. Hypointensity on both SE T2-weighted and enhanced SE T1-weighted images was a characteristic pattern on long-term follow-up MR images in 21/26 unresected lesions; this finding was correlated with devascularization at angiography; the presence of hyperintense areas on SE T2 weighted and enhanced SE T1-weighted images corresponded to the persistence of hypervascular (viable) areas at angiography. PMID- 7878242 TI - [Treatment of primary hepatocarcinoma with chemoembolization and alcohol injection. Personal experience]. AB - The comparative efficacy of transcatheter arterial chemoembolization and percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC) was investigated in a series of 243 consecutive patients: 146 of them were submitted to 1-6 chemoembolization sessions at 1 and 3 months' intervals and 30 to PEI; the remaining 67 patients refused any treatment. The follow-up ranged 3 to 36 months. Survival rates were statistically analyzed with the life table analysis. Patients' survival was affected by the number of nodules and by Child's and Okuda's classes; no relationship was found between survival rates and histologic grade or nodule vascular feeding. In case of single lesions, chemoembolization was more effective than PEI in Okuda's class I. In case of multifocal HCC, chemoembolization was better than no treatment in Okuda's class I and Child's class A. In conclusion, we suggest chemoembolization as the treatment of choice in Child A or Okuda I patients with multifocal HCCs, while its use seems of little help in Child B-C or Okuda II-III patients. In case of unifocal HCC, PEI or surgical resection should be combined with chemoembolization. PMID- 7878243 TI - [Transjugular intrahepatic portasystemic shunt (TIPS). Role of ultrasonographic methods]. AB - The transjugular intrahepatic portosystemic shunt (TIPS) is a new interventional radiology procedure which may be assisted by modern ultrasound techniques (US). Color-Doppler US can be used for patients selection, during TIPS and in the follow-up. In a 20-month period, 71 patients were examined: 3 of them were excluded because of the absolute contraindications shown by US; in 14 of the remaining 68 patients, US demonstrated relative contraindications, such as hepatocellular carcinoma, partial portal vein thrombosis and right internal jugular vein occlusion. During the maneuver, US helped to select the most adequate veins for shunt creation and was especially useful in guiding portal vein puncture, thus allowing technical success to be achieved in 65/68 patients. The mean number of passes per patient was 2.7 and no procedure-related complications were observed. US was also used to investigate TIPS patency the day after the maneuver and to monitor shunt function during the follow-up. Color Doppler US correctly diagnosed both 3/65 early occlusions and 9/65 late stenoses; in particular, in 18/65 patients US showed gradual flow reduction through TIPS, but clinical and endoscopic findings of malfunction appeared only in 9/65 patients whose mean reduction rates exceeded 50% at Doppler US. PMID- 7878244 TI - [Transcatheter arterial chemoembolization technique in cirrhotic patients with hepatocarcinoma. Considerations on the procedure and evaluation of survival]. AB - Two hundred and eight cirrhotic patients with HCC underwent TACE with a standardized technique. Kaplan-Meier survival rates and 12, 24 at 36 months were 62%, 44% and 25%, respectively. Compared with 407 untreated patients, our series had a longer life expectancy, i.e., from 15 months after treatment on. Life experience was statistically different with the L-R test between the groups selected by Child-Pugh cirrhosis staging (p = 0.00000); all 8 Child-Pugh C patients died within 7 months; a high statistical difference was found between Child-Pugh A and B groups (p = 0.00012). Life experience was statistically different with the L-R test between the four groups selected by tumor size and spread (p = 0.012); statistical significance was not reached between contiguous groups in group vs. group comparisons. The patients with monofocal tumors, regardless of size, survive longer than those with multifocal and infiltrative (p = 0.0010) and those with multifocal (p = 0.0029) lesions. Hazard analysis, according to the stratified Cox model, proved tumor-size and Child-Pugh staging to be prognostic factors (p = 0.00027; p = 0.00000) which exhibit a highly significant correlation with each other (p = 0.00000). With the proportional hazard Cox model, tumor characteristics and Child-Pugh stage resulted to be highly significant independent prognostic factors (p = 0.013 and p = 0.000, respectively). Patient survival rates were graphically plotted against literature rates in 407 untreated patients classified by tumor size and by the Child-Pugh method: the two-year survival rates were higher in the subgroups of patients submitted to TACE. To conclude, TACE is an effective treatment not only for multifocal HCCs, but also for large monofocal and infiltrative HCCs. In contrast, TACE is quite useless in the patients with Child-Pugh C cirrhosis. PMID- 7878246 TI - [A radiological study of the acromial arch in shoulder impingement syndrome. Proposal of a variant in Neer's projection]. PMID- 7878245 TI - [Percutaneous alcohol injection in hyperparathyroidism. Experience in 11 cases with an 18-month follow-up]. AB - The authors report the results of US-guided percutaneous ethanol injection into parathyroid glands of 11 patients with primary (2) and secondary (9) hyperparathyroidism. Selection criteria for choosing ethanol treatment were the patient's refuse of surgery and high surgical risks for age or severe chronic intercurrent conditions. At 18 months' follow-up, PTH serum levels had normalized in 2 primary and 2 secondary hyperparathyroidism patients; in all the others but one, PTH levels markedly decreased--always > 50% relative to pretreatment values. Serum calcium and phosphorus levels also decreased, which was not always the case with alkaline phosphatase. After injection, the glands became progressively hyperechoic, gland volume decreased and calcifications appeared. Parenchymal flow disappeared on color-Doppler US images. This study confirms the capabilities of US-guided ethanol injection in hyperfunctioning parathyroids, even though complications may occur and the condition recur. This method is thus suggested as an effective alternative to surgery. PMID- 7878247 TI - [Anesthesiological problems in magnetic resonance]. AB - A prospective study was carried out on 68 patients examined with Magnetic Resonance Imaging (MRI) under general anesthesia. Mean patients age was 10 years (range: 9 days to 77 years). MRI was performed with a 1.5 T superconductive magnet and different anatomical regions were studied: the brain in 63 cases, the lumbar spine in 3, the cervical spine in 1 and finally the upper abdomen in 1 patient. The patients 0-10 years old were anesthetized with isoflurane, while those 11-77 years old were given i.v. propofol and isoflurane. Severe complications occurred in 2 patients only (3%): a 3-year-old child presented respiratory depression and a 21-year-old man had a bronchospasm. Minor complications occurred in 5 more patients. Image quality was excellent in 75% of cases, while few movement artifacts were observed in the extant 25%. To conclude, isoflurane anesthesia is a safe, effective and efficient type of sedation for the patients to be submitted to MRI which can be used also on an outpatient basis. PMID- 7878248 TI - [Do radiologists develop perceptual learning contrast sensitivity?]. AB - A slight difference in brightness between objects close to each other and with no clear-cut outlines separating them can be recognized by the visual function called contrast sensitivity. This function is particularly developed in the radiologist, whose task is to analyze images in many shades of grey and with no clear-cut outlines, due to kinetic and radiogeometrical shading. Assuming that professional habit might develop this function, the authors compared contrast sensitivity in a group of 26 radiologists with contrast sensitivity in a control group (30 non-radiologists). The Vistech VTCS 6500 test was chosen for the task because of its practicality and reliability. The test consists in the recognition of the orientation of 5 series of alternate bright and dark lines differencing in thickness and contrast. The results obtained in the two groups were studied and compared with the statistical test of the analysis of variance, the T-test by Student and the U-test by Mann-Whitney. Contrast sensitivity was surprisingly higher in the radiologists group, in 4 of 5 series of images with bright and dark lines, than in controls and the difference was statistically significant: p < 0.001 with the test and the U-test. A deviation standard increase in contrast sensitivity was found also in radiologists with short-term professional activity (a few years). To explain these results, two hypotheses one suggested by the authors: radiologists pay greater attention to image details, because of their profession; perceptual learning--that is an improvement in the image-research cortical function--might occur, because of constant training. In the radiologist to conclude repeated stimulation of research capabilities in low-contrast images is thought to improve the efficiency of this cortical function. PMID- 7878249 TI - [Brachytherapy in choroid tumors]. AB - Even though brachytherapy has been used for many years to treat choroidal tumors, it is not a widespread technique because it requires much organization and operators skills. The most common methods use 60Cobalt and 106Rutenium plaques, or custom-made plaques with 125Iodine loaded seeds. Another, less common, technique uses 192Iridium wires loaded on custom-made plaques. The technique we used to treat 4 retinoblastomas and 2 choroidal melanomas uses 192Iridium wires loaded on custom-made plaques. The applicator is made of a quick drying paste poured over a sphere the same size as the eye-ball: plastic tubes are inserted, according to preliminary dosimetric measurements, to house the Iridium wires. The applicator is positioned on the eye-ball corresponding to tumor site by surgery. The Iridium sources are inserted into the plastic tubes at the end of surgical placement: this afterloading technique guarantees maximal staff protection. 192Iridium (320 keV gamma emitter) allows the dose to be transmitted deeper than with 125Iodine (30 keV gamma-emitter) and 106Rutenium (3540 keV beta-emitter). Therefore, with Iridium, the dose delivered is lower on the eye-ball surface for the same tumor dose. On the other hand, the use of 60Cobalt (1250 keV gamma emitter) gives the healthy surrounding tissues higher doses. To conclude, this method allows us to customize the application to every single case, to reach posterior sites, to ensure radioactive protection to staff thanks to afterloading and to obtain a good depth to surface dose ratio. PMID- 7878251 TI - [Progressive diaphyseal dysplasia (Camurati-Engelmann syndrome). Early diagnosis in a 2-year-old child]. PMID- 7878250 TI - [Magnetic resonance diagnosis of Hallervorden-Spatz disease]. PMID- 7878252 TI - [Extralobar pulmonary sequestration. A case report]. PMID- 7878254 TI - [Traumatic rupture of anterior crura of the diaphragm with intrathoracic herniation of omental fat. A case report]. PMID- 7878253 TI - [Carotid glomus tumors. Study of 2 cases using color Doppler ultrasonography]. PMID- 7878255 TI - [Preoperative and postoperative magnetic resonance study in a case of leiomyoma of the renal hilum]. PMID- 7878256 TI - [A rare case of bilateral emphysematous pyelo-uretero-cystitis]. PMID- 7878257 TI - [Use of a Dacron-covered metallic stent (Cragg stent) in percutaneous exclusion of voluminous iliac pseudoaneurysm]. PMID- 7878259 TI - [Ticks: a hundred years as a vector]. PMID- 7878258 TI - [Systemic air embolism following percutaneous lung biopsy. A case report]. PMID- 7878260 TI - [Central nervous system cryptococcosis in 10 patients with systemic lupus erythematosus]. AB - Central nervous system compromise is a major cause of morbidity and mortality in SLE. The clinical picture of cerebral cryptococcosis is non-specific and can be mistaken for lupic activity. A retrospective study was undertaken with 10 patients with SLE and cryptococcal meningitis compiled in a 23-year period. The most common symptoms were fever and headache. Lymphocyte counts ranged from 169 to 912 cells/mm. An average delay of 13.6 days in diagnosis was observed in patients with cryptococcal meningitis with no complications and an average delay of 52.4 days in patients with complications. Low lymphocyte counts, observed in all patients, was considered a possible risk factor for cerebral cryptococcosis. To note the association between the delay in the correct diagnosis and complications derived from cerebral cryptococcosis. PMID- 7878261 TI - [Anti-ribosomal antibodies in systemic lupus erythematosus]. AB - OBJECTIVES: To compare indirect immunofluorescence (IIF) with immunoblotting (IB) in the detection of antiribosomal antibodies (anti-P Ab) in patients with systemic lupus erythematosus (SLE) and to investigate the possible association between anti-P Ab with serological and clinical findings in SLE, particularly with neurological manifestations. METHODS: Serum specimens from 44 SLE patients and 10 healthy subjects were investigated for anti-P Ab using IB and IIF in rat triple substrate and HEp-2 cells. In SLE patients measurements were made of antinuclear Ab, anti-DNA ds Ab, anti-Sm Ab, anti-U1RNP Ab, anti-Ro Ab, and anti La Ab. Clinical manifestations of SLE were collected retrospectively when the serological investigation was made. RESULTS: Of the 44 serum specimens tested, 9 showed a ribosomal pattern with triple rat substrate; 8 of them were IB positive (sensitivity 88%; specificity 97%); 12 serum specimens showed a ribosomal pattern with HEp-2 cells by the IIF technique, 9 were positive by IB (sensitivity 100%; specificity 91%). All ten healthy subjects were negative both with IIF and with IB. The nine patients with anti-P Ab in IB (20.45%) had anti-Ro Ab (55% vs. 37%), Anti-Sm Ab (33% vs. 22%, and U1RNP Ab (33% vs. 20%) more frequently than the 35 negative cases. Central nervous system disease (33 vs. 14%), and particularly seizures (33% vs. 5%) and psychosis (22% vs. 8%) were more common in cases with anti-P Ab, but as with serological associations, none of them reached a statistical signification. CONCLUSIONS: IIF with both rat triple substrate and HEp-2 cells is useful for the presumptive diagnosis of anti-P Ab in patients diagnosed with SLE. No significant serological or clinical association was found in patients with anti-P Ab, although neurological disease was more common in these cases. PMID- 7878262 TI - [Invasive pulmonary aspergillosis. Necropsy series]. AB - Invasive pulmonary aspergillosis (IPA) is a severe infection which is usually diagnosed at postmortem examination. This infection occurs mainly in immunosuppressed patients, although it has also been reported in immunocompetent patients. Clinical records from patients diagnosed with IPA in our institution from 1983 to 1992 were retrospectively studied to analyse clinical and therapeutical characteristics of IPA. Sixteen episodes of IPA were recorded, all of them but one from necrotic specimens. A total of 18.7% of patients were immunocompetent, one patient had the acquired immunodeficiency syndrome (AIDS), and the remaining patients had a classical immunosuppression. Fever and dyspnea were noted in all patients; hemoptysis was recorded in 12.5% of patients. The predominant radiological pattern was a bilateral alveolar infiltrate (75%). Diagnosis was made at postmortem examination in 15 cases (93.7%), and a clinical premortem suspicion was obtained only in 25% of patients. IPA can occur in immunocompetent patients more frequently than considered until now. The suspicion index for IPA is low, even in immunosuppressed patients. PMID- 7878263 TI - [Dermatomyositis and head and neck neoplasia]. AB - The incidence of malignant disease appears to be increased in patients with dermatomyositis, although the relationship between dermatomyositis and cancer is still controversial. The most frequently associated tumors are not different from the tumors observed in the general population. There are very few cases of head and neck cancer associated with myositis reported in the medical literature despite the high incidence of these tumors in western countries. Two new cases are reported and the relationship between myositis and cancer is discussed. PMID- 7878264 TI - [Catastrophic antiphospholipid syndrome. Presentation of a case]. AB - The case of a 35 years old female patient is here reported. Her previous medical records included repeated miscarriages and ischaemic ulcers in the right leg. She developed thrombosis at the left common femoral artery with serum antiphospholipid antibodies. The patient was treated with anticoagulants and two months later developed multiorganic failure. She was successfully managed with plasmapheresis, high dose prednisone, and anticoagulants. The clinical picture was considered to be a catastrophic antiphospholipid syndrome. PMID- 7878265 TI - [Lyme borreliosis: diagnostic criteria. Lyme borreliosis study group]. PMID- 7878266 TI - [Pain and functional impairment in both lower limbs. Unusual findings]. PMID- 7878267 TI - [Multiple verrucous lesions in an elderly patient]. PMID- 7878268 TI - [Biological basis of autoimmunity]. PMID- 7878269 TI - [Current status of Lyme disease in Spain: clinical and epidemiological aspects]. PMID- 7878270 TI - [Hughes syndrome: anticardiolipin or antiphospholipid]. PMID- 7878271 TI - [Treatment of systemic lupus erythematosus]. PMID- 7878272 TI - [Malignant mediterranean boutonneuse fever: persistence of the parasite vector and prognostic implication]. PMID- 7878273 TI - [Paromomycin in the treatment of cryptosporidiosis]. PMID- 7878274 TI - [Laparoscopy and hepatic regenerative nodular hyperplasia]. PMID- 7878275 TI - [Portal thrombosis and primary antiphospholipid syndrome]. PMID- 7878276 TI - [Anticardiolipin antibodies in parenteral drug addicts: relationship with HIV]. AB - The IgG isotype of anticardiolipin antibodies (aCL) and its possible relationship with the immunodeficiency virus (HIV) were studied in 65 parenteral drug addicts (PDA). Thirty-seven patients were infected in the present study. Nineteen (51%) fulfilled diagnostic criteria of AIDS. Thirty-two of these 37 HIV-positive patients (86%) were IgG-aCL positive. Fourteen (50%) of the 28 HIV-negative patients were IgG-aCL positive. Our study reveals a lack of correlation between aCL and thrombocytopenia. None of the patients had thromboembolic complications. In AIDS patients no relationship was found between IgG-aCL levels and the presence of Pneumocystis carinii, other infections by opportunist microorganism, and clinical deterioration. Highly increased levels of IgG-aCL (> 80 GPL) were observed in three patients with AIDS and infectious endocarditis. In conclusion, given the non-specificity of aCL en PDA, it is our opinion that its measurement is of little help in daily clinical praxis. PMID- 7878277 TI - [Complete or incomplete revascularization. The influence of the terminology on clinical practice]. PMID- 7878279 TI - [The therapeutic options in postangioplasty coronary restenosis. The viewpoint of a surgeon]. PMID- 7878278 TI - [The therapeutic options in postangioplasty coronary restenosis. The viewpoint of the intervening cardiologist]. PMID- 7878280 TI - [A quantitative study of the structural anomalies in the pulmonary vessels by pulmonary biopsy in children with an interventricular communication]. AB - INTRODUCTION: Pulmonary vascular disease occurs in patients with cardiac anomalies and left to right shunt as the cases of interventricular heart defects. The hemodynamic study of the structural changes and their relationship with the pathological lesions are useful to know the state of the pulmonary vessels and to establish the postsurgical patients outcome. METHODS: We analyzed the morphologic and morphometric data in 17 lung biopsies from children under three years with ventricular septal defect, focused the histologic study in grading the structural changes of the intima, media and adventitial vascular walls and the morphometric evaluation on the thickening of the media and the number of the intracinar arteries. RESULTS: There are significant statistical correlation among the pulmonary pressure and the age, the vascular resistances and the age, the cocient between the pulmonary arterial pressure and the systemic pressure and the external vascular diameter, the cocient of the pulmonary and systemic fluxes and the thickening of the media and finally between the pulmonary vascular resistances and the external arterial diameter. CONCLUSIONS: Our results suggest that the intracardiac repair is desirable within 6 months of life and lung biopsy should be undertaken because is the only way to determine the medial thickening and his muscular of fibrous proliferation that will clarify the post-surgical patients outcome. PMID- 7878281 TI - [The follow-up of transposition of the great arteries corrected by Senning's technic]. AB - INTRODUCTION AND OBJECTIVES: The incidence of late complications after a physiological correction of the patients with transposition of the great arteries (D-TGA) is very significant, due to the alternative operation of the arterial switch. METHODS: We studied 125 patients with D-TGA, treated with Senning surgical correction between december of 1978 and november of 1990. Surgery was performed at a mean age of 11.7 months (from 7 days to 11.2 years), and the postoperative mean follow-up was 7.3 years (from 1.4 to 14.3 years). We analyzed their evolutive clinical condition, ECG, Holter and echocardiogram-Doppler. Four groups were defined: A) Simple, 48.8%. B) Associated with ventricular septal defect, 22.4%. C) With pulmonary stenosis, 15.2%. D) Both anomalies, 13.6%. RESULTS: Sixteen children died (12.8%), 11 of them on the postoperative period. The remaining 5 patients died, at a mean time of 34.3 months after surgery, because they were in cardiac failure. All of patients had enlargement of right ventricle and tricuspid regurgitation was observed in 39 children. There were 3 reoperations. Atrioventricular block was observed in 5.7% of the patients, 33.3% were not in sinus rhythm, 6.6% had atrial flutter-fibrillation, sinus node dysfunction was observed in 24.7%, and five permanent pacemakers were implanted (4.7%). CONCLUSIONS: The later mortality is not high, and the clinical outcome is good, but the frequent rhythm disturbances and enlargement of the right ventricle could let us conclude the hypothesis that anatomical correction is an optimal alternative procedure. PMID- 7878282 TI - [Prolonged treatment with isosorbide-5-mononitrate in patients with silent ischemia]. AB - INTRODUCTION AND PURPOSES: The purpose of this study was to check the beneficial effect of isosorbide-5-mononitrate (IS-5-MN) in patients with myocardial postinfarction silent ischemia, and to evaluate the possible appearance of tolerance after prolonged treatment. METHODS: We have studied 20 patients, all males, with a history of infarction (11 with inferoposterior infarction and 9 with anterior infarction) and having a positive effort test by electrocardiographic criteria (ischemic S-T depression > 1 mm). The study was designed in two parts, first crossover with placebo, double-blind and then open during 100 days; until day 20, 40 mg/12 hours of IS-5-MN were administered and from then on 40 mg/8 hours of the drug. Effort tests were carried on days, 1, 20, 34 and 100, first basal ones and then at 3 and 6 hours after the administration of the medication. RESULTS: The time of S-T segment depression was prolonged in relation to the tests carried out with placebo and to its basal values (Placebo basal: 235 +/- 97, Placebo-3 hours: 196 +/- 92, Placebo-6 hours: 201 +/- 80, day 1-basal: 197 +/- 84, day 1-3 hours: 420-96, day 1-6 hours: 381 +/- 93, day 20 basal: 221 +/- 81, day 20-3 hours: 384 +/- 121, day 20-6 hours: 389 +/- 112, day 34-basal: 272 +/- 91, day 34-3 hours: 437 +/- 102, day 34-6 hours: 362 +/- 100, day 100-basal: 269 +/- 102, day 100-3 hours: 389 +/- 112, day 100-6 hours 369 +/- 111). The duration of the effort was prolonged in relation to the placebo values (Placebo-basal: 480 +/- 100, Placebo-3 hours: 445 +/- 73, Placebo-6 hours: 430 +/ 79, day 1-basal: 450 +/- 95, day 1-3 hours: 510 +/- 79, day 1-6 hours: 532 +/- 86, day 20-basal: 524 +/- 93, day 20-3 hours: 535 +/- 77, day 20-6 hours: 519 +/- 77, day 34-basal: 517 +/- 85, day 34-3 hours: 567 +/- 87, day 34-6 hours: 558 +/- 94, day 100-basal: 520 +/- 89, day 100-3 hours: 593 +/- 91, day 100-6 hours: 590 +/- 92). This effect lasted throughout the 100 days of the study. CONCLUSIONS: Therefore, in patients with silent ischemia after myocardial infarction, the administration of 40 mg/12 hours as well as of 40 mg/8 hours of IS-5-MN shows an obvious anti-ischemic effect; with long-term treatment, the effect persists without evidence of tolerance phenomenon. PMID- 7878284 TI - [Cardiovascular pharmacology (VIII). The role of HMG CoA reductase inhibitors in the current treatment of hyperlipidemias]. PMID- 7878283 TI - [Adenosine triphosphate in the treatment of supraventricular paroxysmal tachycardia: a comparison with verapamil]. AB - AIMS: There are multiple drugs options in the treatment of Paroxysmal Supraventricular Tachycardia (PST) after inefficacious vagal stimulus. In this study we compare two of these treatments: verapamil versus adenosin triphosphate (ATP). METHODS: Fifty patients with PST were randomly treated with either Verapamil (5 to 10 mg) or ATP (5 to 20 mg). The basal features of each group, and the efficacy and safety of the two drugs were compared. Verapamil failures were treated with ATP and vice versa. RESULTS: The characteristics of both groups of treatment were similar. 86% of PST episodes were resolved with Verapamil use, versus 83% after ATP administration. Finally all patients were successfully treated with these drugs. No adverse effects were observed with Verapamil, whereas these effects were frequent with ATP use, but in any case requiring specific intervention. CONCLUSIONS: Both Verapamil and aTP are an equally safe and effective treatment of PST, but transient and minor side effects are frequent after ATP administration. PMID- 7878285 TI - [Ventricular functional changes following an episode of accidental electrocution]. AB - We present a case of accidental electrocution in a 62-years-old male. After the accident he referred a non-specific thoracic pain that disappeared in a week, remaining asymptomatic since then. On the other hand, he shows a permanent electrocardiographic pattern of anterolateral subepicardial ischaemia. Myocardial function revealed by echocardiography and pertechnectate gammagraphy, showed an early primary damage, with a posterior slow tendency to recovery. Exercise treadmill test and Tallium-Dipyridamole test were normal, so an ischaemic background could be rejected in this case. No other diseases were presented, so the changes observed could be exclusively connected with the electrical accident. PMID- 7878286 TI - [An aneurysm in a balloon-catheter-dilated Blalock-Taussig fistula]. AB - The development of aneurysm at the Blalock-Taussig shunt, dilated two years before is described. It is rounded with a diameter of 19 mm. and located at the junction of the right subclavian artery and the right pulmonary artery, that is, at the site of previous balloon dilatation. We think that the pathogenesis is the same as that of the aortic aneurysms which develop after the balloon catheter dilation at the same level. The actual prognosis is unknown being an undescribed pathology. PMID- 7878287 TI - [Surgical cryoablation in a child with malignant ventricular tachycardia refractory to drugs and radiofrequency ablation]. AB - A ten-months-old child with incessant monomorphic ventricular tachycardia is presented. Tachyarrhythmia is refractory to antiarrhythmic drugs and refractory to endocardial radiofrequency current ablation. Epicardial cryoablation of arrhythmogenic area without artificial circulation resulted in the abrupt termination of tachycardia. No tachyarrhythmias were inducible postoperatively. The reduction of ventricular rate by surgical cryoablation does produces resolution of the arrhythmia-induced cardiomyopathy. PMID- 7878288 TI - [A report on the current status and new directions in cardiac electrostimulation]. PMID- 7878289 TI - Cytokines as mediators of hypercalcemia of malignancy. PMID- 7878290 TI - Clinical picture of humoral hypercalcemia of malignancy. PMID- 7878291 TI - Hypercalcemia associated with hematologic malignancies. PMID- 7878292 TI - Differential diagnosis of hypercalcemia: laboratory assessment. PMID- 7878293 TI - Drug therapy of hypercalcemia due to malignancy. PMID- 7878294 TI - Humoral hypercalcemia of malignancy: role of parathyroid hormone-related protein. PMID- 7878295 TI - In vivo models of hypercalcemia of malignancy. PMID- 7878297 TI - Epidemiological aspects of hypercalcemia of malignancy. PMID- 7878296 TI - Morphological characteristics of tumors with humoral hypercalcemia of malignancy: functional morphology of PTHrP. PMID- 7878298 TI - Building an informatics training program for pathology. PMID- 7878299 TI - Automated Speech-recognition Anatomic Pathology (ASAP) reporting. AB - Artificial intelligence speech-recognizers integrated with Laboratory information and Telefaxcommunication Systems have allowed for totally automated surgical pathology reporting. Automated Speech-Recognition Anatomic Pathology (ASAP) reporting improves the speed, text accuracy, comprehensiveness, and workflow management of diagnostic reports while eliminating support personnel. Healthcare reform goals of increased productivity and economy are furthered. Reports are rendered "as soon as possible" (ASAP) expediting appropriate clinical management and decreased length of stay and hospital costs. PMID- 7878300 TI - Standardization of the surgical pathology report: formats, templates, and synoptic reports. AB - The most important routine vehicle for communication in surgical pathology is the specimen report. Although accuracy, clarity and thoroughness are the main goals, significant variability in format and content exists. In an effort to make reports more consistent, several mechanisms are useful and amenable for use in a computerized environment. These include templates, checklists, and tabular data reporting in the form of so-called synoptic reports. Such mechanisms are designed to ensure that critical information can be obtained consistently and easily from the report regardless of the institution of origin. Standardization is most easily extended to specific types of specimens, such as those resulting from mastectomies or colectomies with malignant neoplasms. The ultimate goal of the mechanisms discussed herein is to attain uniformity and consistency of included data found to be relevant to clinical management of patients. PMID- 7878301 TI - Distribution of surgical pathology reports by a computer-driven telephone facsimile (FAX) device. AB - The current environment of medical economics increasingly mandates that written reports on surgical pathology specimens be distributed as soon as they are verified by responsible staff members and that they find their way infallibly to clinical physicians attending the patients in question. This brief overview describes the institutional experiences of the authors in managing this aspect of data delivery at large teaching hospitals. A system for FAX-transmittal of surgical pathology reports is described, used in conjunction with a commercial computer software package that was designed explicitly for anatomic pathology. PMID- 7878302 TI - A pathologist-designed imaging system for anatomic pathology signout, teaching, and research. AB - Pathology images are derived from gross surgical specimens, light microscopy, immunofluorescence, electron microscopy, molecular diagnostic gels, flow cytometry, image analysis data, and clinical laboratory data in graphic form. We have implemented a network of desktop personal computers (PCs) that allow us to easily capture, store, and retrieve gross and microscopic, anatomic, and research pathology images. System architecture involves multiple image acquisition and retrieval sites and a central file server for storage. The digitized images are conveyed via a local area network to and from image capture or display stations. Acquisition sites consist of a high-resolution camera connected to a frame grabber card in a 486-type personal computer, equipped with 16 MB (Table 1) RAM, a 1.05-gigabyte hard drive, and a 32-bit ethernet card for access to our anatomic pathology reporting system. We have designed a push-button workstation for acquiring and indexing images that does not significantly interfere with surgical pathology sign-out. Advantages of the system include the following: (1) Improving patient care: the availability of gross images at time of microscopic sign-out, verification of recurrence of malignancy from archived images, monitoring of bone marrow engraftment and immunosuppressive intervention after bone marrow/solid organ transplantation on repeat biopsies, and ability to seek instantaneous consultation with any pathologist on the network; (2) enhancing the teaching environment: building a digital surgical pathology atlas, improving the availability of images for conference support, and sharing cases across the network; (3) enhancing research: case study compilation, metastudy analysis, and availability of digitized images for quantitative analysis and permanent/reusable image records for archival study; and (4) other practical and economic considerations: storing case requisition images and hand-drawn diagrams deters the spread of gross room contaminants and results in considerable cost savings in photographic media for conferences, improved quality assurance by porting control stains across the network, and a multiplicity of other advantages that enhance image and information management in pathology. PMID- 7878304 TI - Computer-assisted instruction in pathology residency training: design and implementation of integrated productivity and education workstations. AB - Computer-assisted instruction (CAI) has been significantly advanced by the development of inexpensive multimedia personal computers (PCs). As a part of efforts to integrate PC workstations as the primary interface to the anatomic pathology information system, we undertook an evaluation and implementation of image-based resident workstations drawing on technology and software now available. The goal was to develop an integrated diagnostic and research data center using PC workstations. After considerable analysis we implemented a Resident's Resource Center (RRC) to augment the training environment of the resident pathologist by providing productivity tools for the writing, research, and presentation needs of the trainee. We also provided video- and text-based education applications specifically tailored to the training pathologist. This led to the creation of two types of Windows-based workstations. The Productivity Workstation consists of a flatbed scanner, laser printer, and photorecorder connected to a 486-type PC. The Education Workstation consists of a high resolution monitor and video disc player with bar code scanner connected to a 486 type PC. We briefly review the literature concerning CAI in pathology; outline the hardware, software, personnel and cost concerns that we faced in setting up our RRC; provide a partial list of vendors and programs currently on the market; review the software we have installed; and discuss the results of our efforts. PMID- 7878303 TI - Clinical laboratory automation: concepts and designs. AB - Compared with other industries, automation in the healthcare arena has been slow to evolve. Changes in reimbursement for services provided are forcing hospitals and other healthcare providers to look for more cost effective mechanisms to provide all forms of health related services. Clinical laboratory services are essential to the support of hospital operations and most clinic operations. The current paradigm for clinical laboratory operations is based upon a mix of both batch and random access testing and is highly dependent upon clinical laboratory personnel. Changes in the paradigm for clinical laboratory operations may result in a significant cost savings when fully implemented while maintaining a high level of quality and service for the patients. Several different laboratory organization structures are discussed. The Nebraska automation project is described including the development of a modular conveyor system, the use of automated guided vehicles, software, and network architectures. Future directions for the development of clinical laboratory operations including the creation of a "docking device" to link automation systems to instruments is proposed. PMID- 7878305 TI - E-mail, the Internet, and information access technology in pathology. AB - In the Age of Information, the Internet has become a fast, powerful, international information resource that has forever transformed the way we view and use information. The need to quickly access, search, and manage information has grown into a challenging task as the amount of information that is available has grown exponentially over the past few years. As people venture onto this growing information superhighway, traveling may be fast and easy for the expert user, but for most, the trip can be intimidating. For the pathologist who faces overwhelming amounts of printed information today, there is an increasing need for tools to manage medical informatics. The Internet has become the toolbox for many to efficiently search, find and manage information. However, just as the information itself steadily becomes more and more abundant and complex, the Internet continues to grow more and more sophisticated. This sophistication oftentimes leads to more confusion and may actually limit its potential to users. In an attempt to demystify the Internet, this article will discuss its basic features and functions with a focus on information resources available to the pathologist such as E-mail, Gopher, and the World Wide Web. Knowledgeable use of the Internet and its vast resources will greatly increase the quality of patient care. PMID- 7878306 TI - Transrectal ultrasound and prostate biopsy. PMID- 7878307 TI - Role of ultrasonography in the evaluation of the infertile male. AB - Ultrasonography is an important diagnostic tool in the evaluation of infertile male patients. Used in the appropriate patients, ultrasonography may be helpful in confirming the presence of a clinical varicocele and diagnosing ejaculatory duct obstruction. The accuracy of ultrasonography is operator-dependent and one must be aware of the limitations of this diagnostic modality. It is ideal for the treating urologist to perform his own ultrasonographic studies when possible, particularly TRUS. The interpretation of these studies may be influenced by clinical data not available or familiar to radiologists. However, one should remain cautious about the over interpretation of ultrasonographic studies and refrain from injudicious use of this safe and relatively inexpensive imaging modality. The results of these studies may lead to inappropriate surgical interventions that are expensive and involve significant risk. PMID- 7878308 TI - Role of intraoperative ultrasonography in urology. PMID- 7878309 TI - Pediatric urologic ultrasound. PMID- 7878310 TI - Penile ultrasound. PMID- 7878311 TI - [What is your diagnosis? Seborrheic dermatitis]. PMID- 7878312 TI - [Non-oral administration of progesterone: experiences and possibilities of the transvaginal route]. AB - Recent development of transdermal therapy permits application of estrogen, usually produced in the ovaries, in physiological dosage by means of continuous release from either an epidermal patch or dermal application of a gel. Transdermal therapy with progesterone, however is impossible due to poor dermal absorption and high dose requirements (release from corpora lutea: 25 mg/24 hours). Two other possibilities have been proposed. On one hand it is possible to apply norethisterone-acetate (NETA), another gestagen, epicutaneously. This mode of administration carries the same problems as oral application thus allowing for a dose reduction. On the other hand progesterone can be applied vaginally. This mode leads to significantly higher plasmatic concentrations of progesterone and has effects on the uterine mucosa similar to those in a normal cycle. This modality thus permits application of estradiol and progesterone in a physiological manner by a non oral route. It appears particularly interesting in patients at cardiovascular risk. PMID- 7878313 TI - [The anterior cruciate ligament, an important structure of the knee joint]. AB - The anterior cruciate ligament (ACL) is a crucial structure for a normal kinematic of the knee joint. Its rupture has been thought to present the initiation of a sequel leading to secondary damage of the meniscus and finally to osteoarthritis. Diagnosis of an ACL rupture is based on the history as well as on the physical examination. A positive Lachman-sign is diagnostic for an ACL lesion. The question whether an ACL rupture should be operated or not must be decided individually and is based on the demands of the patient. Conservative treatment includes rigorous physical therapy emphasizing strengthening exercises of the hamstrings and the gastrocnemius muscles as well as prorioceptive training. The indication for reconstruction is given, should instability persist. The timing of the operation is important for the outcome. This paper presents an overview of the literature including the rehabilitation program and a diagnostic concept used by the authors. PMID- 7878314 TI - [Generalized seizure, right hemisyndrome and coma in a 70-year-old alcoholic patient]. PMID- 7878315 TI - [Case from general practice (317). Clinically "silent" abdominal aortic aneurysm]. PMID- 7878316 TI - [C3-C4 propriospinal system: an example of integration in the motor control and a possible pathway for motor recovery]. PMID- 7878317 TI - [Memory and benzodiazepines]. AB - Benzodiazepines (BZs) affect acquisition of new information, while retrieval of already learned information is unimpaired. The variability of this effect is important and depends on the nature of the BZ, its dose, the route of administration and the susceptibility of the subject taking the drug. This last factor depends itself on the anxiety level, the age, and a less known idiosyncratic susceptibility of the patient. Finally, there is probably a partial tolerance for the amnestic action of BZs, which explains the fact that the most dramatic amnesias have been described after administration of a single dose of BZ, taken by a patient unaccustomed to BZs. The value of pharmacocinetic and pharmacodynamic characteristics in predicting cognitive impairment remains misunderstood, even though in clinical practice the greatest amnestic effects have been described with short-acting BZs. The interest of studying BZs induced amnesia rely upon several arguments: first, it can be an harmful side-effect, which could be avoided or at least predicted by a better knowledge of BZs and the synthesis of new and more specific drugs; secondly it is an interesting model of organic amnesia, which could allow a better understanding of normal memory. PMID- 7878318 TI - [Information on the consequences of the discovery of the Huntington disease gene]. PMID- 7878319 TI - [Familial hemiplegic migraine. Localization of a responsible gene on chromosome 19]. AB - Familial hemiplegic migraine is an autosomal dominant disorder of unknown pathogenesis in which the migrainous attacks are marked by the occurrence of a transient hemiplegia during the aura. The aim of our study was the identification of the affected gene. The first step was the chromosomal mapping of the affected gene, for which we used a "candidate gene" strategy. The first candidate gene was the gene responsible for CADASIL. While investigating CADASIL, mapped previously to chromosome 19, we observed that some patients had recurrent attacks of migraine with aura. Although the clinical and neuroimaging features of familial hemiplegic migraine differ markedly from CADASIL, we hypothesized that the same gene could be involved in the pathogenesis of both conditions. We chose two large pedigrees for linkage analysis of familial hemiplegic migraine. A maximum lodsore > 8 was found with two markers that are strongly linked to CADASIL. Multilocus linkage analysis located the affected gene within an interval of about 30 cM on chromosome 19, containing the gene responsible for CADASIL. At this step it's not possible to conclude that CADASIL and familial hemiplegic migraine are due to the same mutated gene. It will be necessary to analyse other familial hemiplegic migraine and CADASIL families in order to reduce the size of their respective interval and ultimately identify the mutated gene(s). PMID- 7878320 TI - [Multimodal or multisensorial agnosia?]. AB - A 75 year-old right handed woman had persistent right homonymous hemianopia and alexia without agraphia caused by a haemorrhagic stroke of the left occipito temporal region. Six months later she suffered sudden onset visual and auditory agnosia, following a second haematoma, contralateral to the first one, in the right occipito-temporal region including the lingual and fusiform gyri. None of the disorders concerned semantic representation, so that an asemantic agnosia was excluded. Her performance in naming and recognition tests, in both visual and auditory modalities, demonstrated a wide range of responses and errors. The pattern of visual symptoms suggested "associative visual agnosia narrow sense" (Farah, 1990); auditory agnosia concerned only the non verbal stimuli. These findings were discussed in terms of anatomical mechanisms subserving perceptual, semantical, visuo and auditory-verbal representation. In this case, visual and auditory, agnosia appears to be independent. PMID- 7878321 TI - [Subcortical dementia of the Neumann type. Contribution of diagnostic imaging]. AB - A 36 year-old patient presented with a dementia of frontal type, gait disturbances, incontinence and a pseudo-bulbar palsy, which caused death at age 40. Brain biopsy of the frontal lobe showed an extensive deep subcortical gliosis. A high level of GFAP was detected by immunoblotting in the biopsy. Clinical and neuropathological observations are similar to cases described as Neumann Progressive Subcortical Gliosis. Single Photon Emission Computer Tomography showed a bilateral frontotemporal hypoperfusion, and Magnetic Resonance Imaging large periventricular and subcortical hyperintensities in both hemispheres, the brainstem and the cerebellum. The hyperintensities on T2 weighted MR images might be related to the intense gliosis. The contribution of such imaging data to diagnosis must be confirmed by other clinico-pathological cases. PMID- 7878322 TI - [Idiopathic putamino-caudal atrophy: a rare cause of hemidystonia]. AB - Hemidystonia, a rare presentation of dystonia, is usually secondary to various insults of the controlateral basal ganglia. The following report describes hemidystonia which occurred at the age of 16 years. Idiopathic atrophy of the controlateral caudate nucleus and putamen seemed to be the only aetiology. PMID- 7878323 TI - [Biopercular polymicrogyria associated with congenital ophthalmoplegia caused by nuclear lesion of the common oculomotor nerve]. AB - Developmental pseudobulbar palsies seem to be different from the adult form described by Foix, Chavany and Marie. They usually include a major speech delay and severe epileptic seizures. In one clinicopathological case, neuroradiological imaging showed a macrogyric aspect of both rolandic operculi and unilateral destruction of pes pedunculari. Microscopic examination showed a four-layered polymicrogyria involving the first temporal gyrus and in the brainstem a selective destruction of the left oculomotor nucleus. Thus, the macrogyric aspect could be related to post migratory disorder occurring late in the cortical development. The brain stem lesion, destroying unilaterally the third cranial nerve nucleus gives a good example of the complex somatotopia of this oculomotor nucleus. PMID- 7878324 TI - [Bacterial abscesses of the spinal cord. Review of the literature (73 cases)]. AB - Intramedullary spinal cord abscesses are an uncommon entity with 73 cases reported in the literature; the first case was reported in 1830. Sixty-seven percent of abscesses occur in the first 4 decades of life. Staphylococcus and Streptococcus are the most common organisms; 25% of patients have negative intraoperative cultures. The primary source of the infection could be found, in only 45% of patients. Most of these infections are secondary to metastatic spread from infections of the lung, endocarditis, genitourinary tract; 10 reports have described an intramedullary abscess secondary to a dermal sinus. The signs and symptoms depend on the location of the lesion; the thoracic spine is the most commonly area involved. Patients are usually divided into three clinical groups; acute onset (symptoms less than 1 wk), subacute onset (symptoms up to 6 wk), and chronic course (symptoms more than 6 wk). Patients with the acute form are more likely to have a fever and an elevated white blood cell count and may show either a partial or complete transverse myelitis picture. The patients with chronic abscesses are less likely to have fever and leukocytosis, and their symptoms often mimic those of an intramedullary spinal tumour. The erythrocyte sedimentation rate tends to be elevated in all patients regardless of their clinical findings. CSF cultures are usually sterile. Plain x-rays of the spine are often normal. A myelogram in conjunction with a computed tomographic scan may show the intramedullary lesion. MRI studies usually demonstrate intramedullary lesions with exceptional clarity; the use of gadolinium with T1-weighted MRI studies enhances the abscess wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878325 TI - [Isolated proximal muscular weakness disclosing myasthenic syndrome]. AB - Three cases of chronic limb-girdle myasthenia gravis (one man and two women) are reported. The duration of the disease was three, five and 20 years respectively. None had oculobulbar weakness during this period nor fluctuating symptoms. The primary diagnosis was myopathy in two cases and myelopathy in the other one. In view of this diagnosis, several features were atypical: absence of marked wasting, preservation of tendon reflexes and normal serum creatine kinase activity. Finally, diagnosis of myasthenia gravis was established by the occurrence of a characteristic decremental muscular response to repetitive stimulation and by positive edrophonium test. It seems that the rate of positivity of acetylcholine receptor antibody is lower than in the common form of the disease. Two patients responded to acetylcholinesterase inhibitors and one to high-doses intravenous human immunoglobulins. These and previous cases described in the literature raise the problem of the definition of an unusual form of myasthenia gravis or of a new type of neuromuscular disease characterized by the presence of distinctive changes on muscular biopsies, specially tubular aggregates as in one of our cases. However, this unusual form of chronic limb girdle weakness has to be recognized because treatments are effective in most cases. PMID- 7878326 TI - [Central pontine myelinolysis disclosed by severe pseudobulbar syndrome without motor involvement of the limbs]. AB - A young alcoholic man, receiving diuretics, developed a marked pseudo bulbar syndrome after rapid correction of hyponatremia. Magnetic resonance imaging demonstrated a central pontine myelinolysis, associated with extra-pontine lesions in both thalami. The patient fully recovered, despite persistent radiologic abnormality. PMID- 7878327 TI - [Hippocampothalamic infarction. A limited form of infarction in the posterior cerebral artery area]. AB - Infarction of the hippocampus and the right ventroposterolateral thalamus was observed. Angiography revealed a posterior cerebral artery occluded near its origin, immediately upstream from the posterior communicating artery. The infarction was limited to the areas irrigated by the branches originating in the proximal part of the artery. More distal branches for the calcarine scissure and the temporooccipital gyruses were not involved. PMID- 7878328 TI - [Visual illusions of obliquity]. AB - Three cases of visual illusion of obliquity were observed. This rare disorder is due to impaired of panorama/vertical orientation. When present, special care must be given during visual correction to spatial orientation of the perceived image in the vertical axis. PMID- 7878329 TI - [Dermatomyositis and Wilson disease]. AB - A 15 year-old girl developed both a dermatomyositis and a Wilson's disease. A clinical remission was obtained with steroids and D-penicillamine. The potential role of cupric intoxication in the pathogeny of the muscular syndrome is discussed. PMID- 7878330 TI - [Lesion of the lingual nerve after tooth extraction]. AB - A case of tongue anesthesia after removal of the lower third molar was observed. This type of lingual nerve injury is often unrecognized by the neurologist. Good knowledge of the anatomy and examination techniques are necessary to help the surgeon in the management of the patient. PMID- 7878331 TI - [New look at problems of assessment and tolerance of certain carcinogens in food in view of the literature]. AB - The present approach to the assessment of carcinogens in food is described in the light of a literature review. In accordance with Delaney clause, these compounds should not be found in food. The advances in analytical methods have shown, however, that it is not possible to avoid the presence of trace amounts of carcinogens, natural as well as synthetic. On the basis of the maximal tolerated dose (MTD) established in animal studies the power of cancerogenic activity of many compounds was determined as expressed by the dose producing cancer development in 50% of the experimental animals. This dose has the symbol TD50, analogously to the LD50 symbol used in toxicology. On the basis of these doses a trial is presented of ranking carcinogenicity++ using a new index HERP which expressed the per cent of the amount of a compound taken with food in relation to TD50. Trials are mentioned also of estimating health risk on the basis of evaluation of the risk of malignancy development due to intake of a compound with food, according to the "de minimis" doctrine. PMID- 7878332 TI - [Contamination of waters by formaldehyde]. AB - The high toxicity of formaldehyde and its relatively high number of release sources called for extensive studies for elucidating its sources and the degree of contamination of waters in Poland with this compound. In the study formaldehyde was determined in community sewage, industrial sewage and precipitations in the street, as well as in surface waters, waters taken for supplying networks and drinking waters. It was tried also to establish the possible influence of meteorological factors on formaldehyde presence in surface waters. Formaldehyde was determined by the colorimetric method with chromotropic acid after previous distillation of the analysed samples of waters and sewage. It was found in these studies that the main source of contamination of surface waters with formaldehyde are community sewage and industrial sewage. In summer the concentration of formaldehyde in these waters was higher than in winter. It is stressed that the maximal values of these concentrations in studied waters were above the acceptable value, even several times. Despite this unfavourable situation it was found that in tap water obtained from rivers this contamination was negligible, and after treatment it contained practically no formaldehyde. Thus formaldehyde in drinking water is not a health risk for the population. PMID- 7878333 TI - [Air pollution by formaldehyde in some Polish cities]. AB - On the basis of won studies and the results reported by selected Sanitary Epidemiological Stations the pollution of atmospheric air with formaldehyde was evaluated. All air samples were obtained by the aspiration method continuously during 24 hours. In the samples formaldehyde was determined by the colorimetric method with chromotropic acid. The obtained results showed that in the highly industrialized parts of the country excessive air contamination was present. The highest proportions of the results exceeding acceptable level were noted in Lodz- 67.8%, and in Silesian cities, such as Dabrowa Gornicza--88.0%, Dzierzoniow- 22.7%, Rybnik--39.0%, Wodzislaw--31.0%, Walbrzych--65%. In urban areas, even with high traffic intensity, no significantly excessive concentrations of formaldehyde in air were found. The proportion of results above the acceptable value was from 0.3 to 9.0%. PMID- 7878334 TI - [Toxic effects of dichlorvos on neutrophils of human peripheral blood in vitro]. AB - The purpose of the study was to assess the phagocytic activity and bactericidal function of human peripheral blood neutrophils exposed to dichlorvos (DDVP) an organic phosphorus pesticide in vitro. It was found that the values of the phagocytosis index in neutrophil cultures incubated with DDVP in doses of 70 microM and 100 microM increased with increasing pesticide concentration and depended on incubation duration (1 h and 2 h). The proportion of non phagocytizing neutrophils remained at a level similar to that in controls. The value of NBT reduction in neutrophils (indicating their bactericidal activity) after 1 hour of incubation with DDVP remained at the level of control values, but after 2 hours it decreased--significantly at DDVP concentration of 70 microM, and at DDVP concentration 100 microM p = 0.05. These results show that DDVP causes in neutrophils a selective stimulation of one step of phagocytosis connected with engulfing of particles, with simultaneous inhibition and/or damage to the mechanisms connected with aerobic killing of microorganisms. PMID- 7878335 TI - Hypocholesterolemic effects of saponins. AB - On the basis of the literature the results of experimental investigations on hypocholesterolemic action of saponins are demonstrated. Also the theories explaining the mechanism of this action are discussed. PMID- 7878336 TI - [Fluorine and lead content in selected vegetables grown within the range of emission of compounds containing these elements by the glass plant"Irena" in Wroclaw]. AB - By means of spectroscopy fluorine and lead were determined in selected vegetables gathered in 1990 from Workers' Gardening Plots "Transportowiec" lying about 500 m from the Irena glass plant and similar plots "Irena" situated about 2600 m from the emitters of the plant. The obtained results were compared with those of similar measurements in the preceding 8 years, and with analogous determinations in the vegetables gathered in 1989 from "Podzamcze" gardening plots in Szczytna in immediate vicinity of the glass plant "Sudety". The study extended over many years showed that in the vicinity of such plants, the soil, the vegetables and fruit are contaminated with fluorine and lead. Moving of "Irena" gardening plots from 50-350 m from the plant to a distance of 1800 m from it caused that only the parts of the vegetables above soil level contained higher amounts of fluorine and lead. Certain above-soil parts of the plants from the "Podzamcze" gardening plots contained fluorine in amounts exceeding the acceptable level. Most vegetables, both roots and higher parts, were contaminated with lead, indicating that the soil was contaminated with lead also. PMID- 7878337 TI - [Estimation of usefulness of selected ion exchangers in elimination of radiocesium from the rat organism]. AB - Cation exchange resins were applied to eliminate radiocesium from rats. The resins were administered intragastrically immediately after contamination 137CsCl and with delay of 1, 2, 6 and 12 hours. Inorganic cation resins applied with a few hours delay after contamination were shown to be highly effective. PMID- 7878338 TI - [Testing effectiveness of selected bio-insecticides for reducing the population of cockroaches (Blattella germanica L.)]. AB - The usefulness was tested of the biological insecticides containing B. thuringiensis available in the market in the eradication of cockroaches. Thuridan was the most effective out of the tested insecticides in reducing the number of the insects. Its higher activity in relation to Thuricide was evident at all tested concentrations. Males were more sensitive than females. On the other hand, no significant response of cockroaches to M-one preparation was noted, since the per cent of dying insects was only slightly higher than in the control group. PMID- 7878339 TI - [Assessment of resistance to permethrin of german cockroaches (Blattella germanica L.) caught in Poland]. AB - Resistance to permethrin was tested in cockroaches caught in health service institutions in various parts of Poland. The tests were carried out by the contact method as recommended by the WHO. The density of the insecticide was 20 mg/m2. The experiment was done only on male insects, calculating the values of LT50 and LT90 in insect groups caught in various localities. These values were compared with LT50 and LT90 values in sensitive insects exposed to the insecticide, and the resistance indices R50 and R90 were calculated. This made possible determination of permethrin resistance of the populations from various areas. The results showed that the sensitivity of the insects varied. Cockroaches caught in Opole, Biala Podlaska, Szczecin, Warsaw were highly resistant to permethrin, while those from Plock, Piotrkow Trybunalski, Chojnow, Nowy Sacz tolerated the insecticide, and those from Jedrzejow were as sensitive as control laboratory insects. PMID- 7878340 TI - [Usefulness of the fruit fly for assessment of mutagenicity of benzene, acetaldehyde and formaldehyde]. AB - Among the contaminants of water, soil and air the number of mutagenic and carcinogenic substances is increasing. For the assessment of health risk connected with the simple and cheap methods are necessary which could detected and measure the mutagenicity of these substances. The widely used tests using prokaryotes give negative results in the tests of certain substances which are carcinogenic in mammals. In the case of benzene and acetaldehyde Ames test gives false negative results, and in the case of formaldehyde the results are equivocal. An advantage of fruit fly Drosophila melanogaster used for this purpose is that its cell structures, enzymes and metabolic processes are similar to those of mammals. For the demonstration of mutagenicity of benzene, acetaldehyde and formaldehyde the test of somatic mutation and recombination SMART was carried out in these flies. The results confirmed the usefulness of the SMART test for the demonstration of the mutagenicity of contaminants in the environment. PMID- 7878341 TI - [Assessment of health conditions in student dormitories in Poland]. AB - The health conditions in all students' hostels in Poland were assessed in 1992 using a standardized set of criteria. The study was carried out by workers from the divisions of children and adolescent hygiene of all sanitary-epidemiological stations in whose areas were the hostels. The data obtained in 1991 were compared with those from the years 1983 and 1977, since the methods, range and organization of these studies were identical in these years. Out of the total number of 388 hostels in the lists supplied by 35 sanitary-epidemiological stations the health conditions were assessed in 382 hostels (98%). The hostels not assessed in this action were those where repair works were conducted. The assessment demonstrated that in the studied period from 1977 to 1991 the health conditions in students' hostels have improved significantly. The observed improvement was due, in a high degree, to reduced number of inhabitants in the hostels, and with modernization of the buildings which had not been built for accomodating students. The shortcomings of the sanitary-hygienic conditions in some hostels suggest the need for undertaking of current and long-term actions for improving artificial as well as natural lighting in dwelling rooms and rooms for reading, providing of optimal conditions for maintenance of personal hygiene, and for conditions of recreation, wherever possible, in the immediate vicinity of hostels. A disquieting tendency is the reduction in the number of students taking meals in students' canteens, with increasing organization of feeding on individual level, which, in view of the present falling economic resources of the population can have serious health consequences. PMID- 7878342 TI - [Value of harmful elements in fruit and vegetables grown in the province of Siedlce]. AB - The content of iron, manganese, nickel, lead, copper, zinc and cadmium was determined by means of atomic absorption spectrometry (ASA) in vegetables and fruit grown in the Province of Siedlce. The studied fruits included tomatoes, cucumbers, cabbages, carrots, parsley, celery, red beets, potatoes garden strawberries, black and red currants, raspberries, apples, plums and cherries. The total number of studied samples of fruits and vegetables was 229. In 49 studied samples cadmium exceeded 0.03 mg/kg and in 4 samples lead was above 0.3 mg/kg. In most studied samples of green parts of parsley and celery (80%) zinc was above 10 mg/kg of fresh mass, that is the level permitted in our country for products containing below 20% of dry mass. PMID- 7878343 TI - [The level of metal impurities in some edible mushrooms growing wild]. AB - The amount of lead, cadmium, copper, zinc and mercury has been determined by atomic absorption spectroscopy in 96 samples of edible mushrooms, growing wild fresh edible fungus and dried (Boletus scaber, ceps) mushrooms, acquired from 6 regions in Poland: Zielonogorskie, Torunskie, Ostroleckie, Radomskie, Warszawskie and Lubelskie in 1990 and 1991. The level was found to be higher than that allowed by the polish standard PN-89/A-78510 Mushroom Processed Foods. Dried mushrooms and other legal acts eg. Instruction of the Ministry of Health section Social Welfare of 12th November 1990, the content of zinc in dried mushrooms (all samples) and in fresh edible fungus from the Zielonogorski and Torunski region. The content of copper in fresh edible fungus did not usually correspond with the requirements, whereas in the dried mushrooms (Boletus scaber, ceps) it exceeded the level only insignificantly in individual samples (average from studied regions was found to be within limits). The content of lead in dried mushrooms complied with the requirements of the standard, except for samples of ceps from Zielonogorski region, where it insignificantly exceeded the allowed level of 2.0 mg/kg. The average content of zinc and copper in dried mushrooms did not exceed the allowed levels. The levels of mercury determined in the studied samples do not cause any excitement in light of the FAO/WHO agreements. A high level of contamination with cadmium was noted in all studied samples, being 2.5 times higher in edible fungus, 6-8 times higher in Boletus scaber and 19-23 times higher in dried ceps.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878344 TI - [Evaluation of cadmium and lead intake from vegetables by the consumer in the province of Katowice]. AB - The amounts of Cd and Pb consumed with vegetables were determined in four groups of households: workmen, workmen-peasants, farmers and pensioned workers and persons receiving disability allowances. The chemical analysis was done, in the first place, of vegetables with edible roots in which Pb and Cd were determined by atomic absorption spectrophotometry. The vegetables were bought in 1986-1987 by the Province Gardeners Cooperative in the Province of Katowice (mining and industrial region) and from the Province of Katowice and Warsaw. The amount of Cd or Pb found in weight unit of a given vegetable multiplied by the amount of this vegetable consumed in a week served as a measure of the amount of these metals taken by the consumer. After comparing of this amount with the acceptable dose the per cent of this dose obtained from vegetables was calculated. The study showed that the vegetables brought from other provinces than Katowice contained several times less Cd and Pb than those grown in the Province of Katowice. The lowest intake of Cd and Pb with vegetables was found in the households of workmen and the highest one in the households of farmers who consumed nearly exclusively vegetables grown on their farms. The vegetables from the Province of Katowice accounted in farmer families for 40% of the acceptable maximal weekly intake of cadmium, and the intake of lead was even above this maximal level. The differences in the weekly intake of these metals between the studied groups of households were due to differences in the amounts of consumed vegetables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878345 TI - [Exposure to lead in selected population groups. IV. Lead exposure among nursery children in Chorzow]. AB - Main goal of this studies was to determine the level of exposure to lead of selected representatives of children's population attended nursery school, aged 2 to 4 years, residing in three different districts of Chorzow as far as the traffic intensity is concerned. It is the most densely populated town in Poland with the high concentration of industry and considerable intensity of traffic. Number of tested samples of children were 41, 43, 40. The tests were made in summer. Lead (Pb-B), zinc protoporphyrin level (ZPP), hemoglobin (Hb), erythrocyte count in blood (E) and delta-aminolevulinic acid (ALA) and creatinine concentration in urine were determined. The highest Pb-B level observed was 300 micrograms/l, the geometric mean of the blood lead concentrations were: 131, 132, and 199 micrograms/l and were not statistically valid in their differences. Median ranges were 118, 133 and 144 micrograms/l. Averages above the level 200 micrograms/l were found in the case of 19.5%, 11.8% and 15% children. Data were estimated in comparison with WHO recommended admissible blood lead level in overall population. The obtained data suggest higher lead absorption in the examined children's population. PMID- 7878346 TI - [Value of calcium and phosphorus in daily food rations of children in two districts of southern Poland]. AB - Calcium and phosphorus content in daily diets for children of the range from 0.5 up to 14.6 years was examined. Children from Bielsko district lived in villages near Zywiec and from Katowice district lived in city Bytom. Results are grouped according to: domicile (city--village), age range (0.5-1.0, 1.0-1.5, 3.5-4.5, 6.5 7.5, 11.4-14.6 years), in the range 11.4-14.6 also according to sex, and according to qualitative evaluation of diet (adequate, poor and inadequate). As can be seen from the presented results amounts of the two elements in the daily diets for children are incompatible with recommended nutritional standards. Discrepancies increase when age of children increases and when qualitative evaluation of the diet decreases. The calcium: phosphorus ration in diets for children is also anomalous with the exception of the age range 1.0-1.5 year. PMID- 7878347 TI - [Comparative analysis of selected nutritional parameters of fat in daily food rations of various population groups. I. General characteristics of fats]. AB - The reported study demonstrated differences of the energy value and fat content between daily food rations. The recommended energy values of daily rations were generally complied with in all groups, but the groups of mental workers and retired workers these values were exceed. The per cent of energy from fat in food rations in all groups was evidently too high exceeding the recommended value by 30%, on average. PMID- 7878348 TI - [Changes in chemical composition of selected food products in the province of Katowice]. AB - The levels of Mg, Fe, Mn, Cu, Pb and Cd were determined in fresh vegetables obtained from central storerooms of the WSO in Katowice which were intended for market in that Province. Vegetable samples were taken from the stores twice in the months from September to March in the years 1986-1987. At the same time similar analyses were done of raw milk and milk for consumption from the market and from certain dairy cooperatives in the Province. Besides the above metals, in the samples dry mass, ash, protein (by Kjeldahl method), calorie values (by burning in calorimetric bomb ZKL-4) were determined. The study included these mineral components which are necessary in human physiological requirements, and those which can be toxic if consumed in excess, and also those which cumulate selectively in plants and in animal and human organisms. The mutual relationships were evaluated of these components in the analysed food products based on calculated correlation coefficients. After the chemical analysis of these products it was found that the levels of Mg, Fe, Cu, Zn, Mn and Cd and Pb varied depending on the product and site of origin of the sample. The levels of heavy metals, such as Cd and Pb, were exceeding the acceptable values in the edible parts of vegetables grown in the Province of Katowice and intended for the market in that Province. The lowest levels of toxic metals and the highest content of mineral components indispensable for physiological functions were found in the vegetables brought from the neighbouring Province of Kielce.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878349 TI - [Content of nitrates and nitrites in early vegetables and potatoes sold in the marketplace of Bialystok in the year 1992]. AB - Nitrate and nitrite were determined in early vegetables and potatoes sold in Bialystok in 1992. The levels of nitrates and nitrites were determined in 248 samples. Nitrate and nitrite were evaluated spectrophotometrically by the method of the Griess reaction, after reduction of the nitrates to nitrites, with cadmium dust. High values of nitrate were found in the early vegetables: lettuce, young red beets, radishes, dills, parsley, carrots, cucumbers and potatoes. The results were higher than the suggested limit in Poland. The nitrite contents, except for carrots, were determined in selected vegetables and potatoes. PMID- 7878350 TI - [Value of nitrates and nitrites in selected vegetables and potatoes sold in the marketplace of Bialystok in the years 1991-1992]. AB - Nitrate and nitrite contents were determined in selected vegetables and potatoes from the market in Bialystok and from ecology cultivation in the years 1991-1992. The modified Griess method was used for determination of nitrate. The results showed that the nitrate contents in red beets, cabbages, parsley, carrots, celery and potatoes, were higher than the suggested limit in Poland. In the group of vegetables from special cultivation plots, the nitrate contents also exceeded the maximal permissible level. Low nitrite concentrations were found in the studied vegetables. PMID- 7878351 TI - [Concentration of selected polycyclic aromatic hydrocarbons and metals in the soil of Krakow]. AB - The concentration of heavy metals and polycyclic aromatic hydrocarbons (PAH) were determined in the soils obtained from various traffic roads in Cracow including surroundings of steel works. The method of atom absorption spectrometry was using to determination of Ca, Mg, Pb, Fe, Zn, Cd, Cu. PAH (fluoranthene, pyrene, benz(a)anthracene + chryzene, benz(a)pyrene, benz(ghi)perylene, fenanthrene and perylene) were determined by gas chromatography. The highest concentration of heavy metals was found in zone of steel works. A steep fall concentration of Fe was observed in the soils with increasing distance from the works. It seems that the variety in concentration of metals don't depend only on vehicular traffic. The highest mean PAH concentration exceeding 800 micrograms/kg of dried soils was found in soil samples taken from roads where the traffic is the highest. PMID- 7878352 TI - [The celioscopic revolution]. PMID- 7878353 TI - [Value of Doppler ultrasonography in the diagnosis of renal artery stenosis]. PMID- 7878354 TI - [Cognitive behavioral therapies]. PMID- 7878355 TI - [Prostatic cancer in the 19th century]. PMID- 7878356 TI - [Epidemiology of colorectal cancer. Prospects of prevention]. AB - Colorectal carcinoma is very common in western countries. It is in the front line of malignant pathology in France. The estimated number of new cases is almost 26,000 per year. The role played by diet in the onset of colorectal carcinomas is well established. The majority of studies indicate the protective role played by green vegetables. The role of other factors remains controversial: protective role of fibres, calcium and vitamins and favourising role of fats, proteins, red meat, alcohol and caloric intake. A number of intervention studies are underway. They should enable the proposal of a primary prevention strategy. The early detection of carcinomas and the secondary prevention of colorectal carcinoma are areas of great interest. Detection of occult blood in stools as a mass screening test is currently being evaluated. It will be necessary to wait for 1 to 4 years before being able to determine the effect on mortality and an even longer period to evaluate the effect on the incidence of colorectal carcinoma. PMID- 7878357 TI - [Colorectal lesions predisposing to cancer]. AB - Precursors of colorectal carcinoma are adenomatous polyps, sporadic or arising in familial adenomatous polyposis and Lynch syndrome and chronic inflammatory lesions related to ulcerative colitis and Crohn's disease. The adenoma-carcinoma sequence is well established and early detection and removal of colorectal adenomas is thought to prevent colorectal cancer in high risk asymptomatic persons, i.e. subjects over 45 years, with personal or familial history of adenomas and colorectal cancers. The precancerous potential of adenomatous polyps varies according to tissue type, with increased risk with the extent of the villous component, high grade of dysplasia, large size greater than 1 cm and multiple adenomas. The development of de novo colorectal cancer from normal mucosa with flat adenomas has been recently emphasized. The risk of colonic cancer in patients with ulcerative colitis and Crohn's disease is controversed. PMID- 7878358 TI - [Genes, heredity and colorectal cancer]. AB - All cancers result from the accumulation of mutations of proto-oncogenes and tumor suppressor genes. Sporadic and familial colorectal cancers result from the accumulation of the following genes, in a relatively stereotyped chronological order: the tumor suppressor gene apc whose mutations are responsible for the familial adenomatous polyposis; the proto-oncogene K-ras which is mutated in 50% of large adenomas (> 1 cm) and adenocarcinomas; the tumor suppressor gene dcc; and the tumor suppressor gene p53 whose inactivation in a factor of bad prognosis. While some of them are induced by mutagens, others result from an instability of the genome. Two types of instability are observed in both sporadic and familial colorectal cancer. The first type, which is found in 25-50% of cases, appears as cytogenetic abnormalities with aneuploidy and allelic losses. The second type of instability is induced by mutations of the hMSH2 or hMLH1 genes which code for proteins involved in the mechanism of DNA repair. PMID- 7878359 TI - [Objectives and means of screening of colorectal cancer]. AB - Despite numerous publications on the subject, the debate over the merits of the various methods available for screening for colorectal cancer is continuing. Choice of the method depends on the patient being treated. In the present state of our knowledge, mass screening by Hemoccult, which is of low cost but of poor sensitivity and only fairly well accepted, cannot be used routinely but must be further evaluated and developed. In persons willing to undergo regular examinations, an annual or biannual Hemoccult examination associated with rectosigmoidoscopy every 5 years appears appropriate. In subjects having a familial history in first-degree relatives, colonoscopic examination every 5 years is adequate. Lastly, in patients with a personal history of cancer or adenoma, screening consists of colonoscopic follow-up adapted to the individual case. PMID- 7878360 TI - [Diagnosis and staging of colorectal cancers]. AB - Early colorectal cancer produces no symptom, thus justifying efforts at detection in screening programs. Symptoms are usually secondary to obstruction, local invasion, perforation or bleeding. Any fecal bleeding must be investigated to rule out a colorectal cancer. The initial imaging study to identify a colorectal cancer is often colonoscopy, which is frequently supplemented with a double contrast barium enema. Once the presence of cancer is histologically proven, the preoperative evaluation includes detection of hepatic and extrahepatic spread, especially with ultrasound and CT scan. Endorectal ultrasonography has been shown to be a significant advance for staging rectal cancer. It provides the best staging in selecting patients for preservation of sphincter function and for adjuvant therapies. The most useful prognostic factors in tumors without distant metastases are the depth of tumor extension, the number of positive lymph nodes and the histologic grade. Preoperative CEA level, vascular invasion and ploidy are also important prognostic factors. PMID- 7878361 TI - [Surgery of cancers of the colon and rectum]. AB - Whatever the technique used for colorectal resection, the carcinologic principles of resection of colorectal cancer must include removal of the cancer with an adequate margin by performing a wide excision of the tumor-bearing area and associated lymphatics. Recent advances in colorectal cancer management concern principally rectal cancer, with new diagnostic tools (i.e. endorectal ultrasound, MRI, CT-scanner), and new surgical procedures (ioff coloanal anastomosis, stapled anastomosis, and local excision) which allow, in most of the cases, a sphincter saving resection to be performed. Indication of laparoscopic surgery in colorectal cancer remains to be determined. Prognosis of colorectal cancer has not improved for recent years and the 5 year survival rate remains close to 50% after surgical excision. However, recently, adjuvant chemo-and radio-therapy have permitted a significant reduction of local recurrences and an improvement of the overall survival. PMID- 7878362 TI - [Adjuvant chemotherapy in cancers of the colon and rectum]. AB - The high incidence of recurrence in patients with resected colorectal cancer at Dukes' stages B2, B3 and C indicates that these patients have micrometastases at the time of surgery and demonstrates the need for adjuvant therapy. Studies using 5-FU alone led to negative results. The combination of 5-FU and levamisole given every week during 1 year was shown to be an effective adjuvant treatment, significantly increasing survival at 5 years from 55% to 71% (p = 0.006). Other treatment modalities are under investigation. Leucovorin increases 5-FU activity in advanced cancers. A combination of the two could thus play an important role in adjuvant treatment. No results are available regarding the compared effects of 5-FU/folinic acid, 5-FU folinic acid/levamisole to 5-FU/levamisole. Portal vein chemotherapy with 5-FU administered during 7 days after surgery has been studies as well, and could also be effective. An association of a short postoperative course of intraportal chemotherapy with intravenous chemotherapy over several months may lead to a further improvement of survival in patients with colorectal cancer. Despite the substantial advances made in the adjuvant treatment of colorectal cancer, progress will be obtained only through continual research. PMID- 7878363 TI - [Radiotherapy of cancer of the rectum]. AB - As soon as there is a tumor extension into the perirectal fibro fatty tissue (T3 stage) the chance to cure the rectal cancer is no more than 65%. The aim of adjuvant treatment is to reduce the risk of local recurrence and metastasis. Postoperative irradiation does not have a definitive effect on local control, and its tolerance is poor; it may not be recommended. The efficacy of combined postoperative irradiation and chemotherapy has not been definitively proved. Moreover, this approach leads to high toxicities and may not be recommended routinely. On the contrary, preoperative irradiation definitely improves the local control, reducing the risk of recurrence up to 50%. It is commonly indicated as soon as the rectal cancer is at the T3 stage. The efficacy of combined preoperative irradiation and chemotherapy is under evaluation. Irradiation is also indicated for patients with rectal cancer at the first stage or as palliative treatment. PMID- 7878365 TI - [Chronic respiratory insufficiency. Etiology, physiopathology, diagnosis, treatment]. PMID- 7878364 TI - [Treatment of metastases of colorectal cancers]. AB - Important advances have been made in the management of advanced colorectal cancers during the past decade, even though prognosis remains poor. Quality of life, and sometimes overall survival have been increased. Surgery is the only potentially curative treatment of liver metastases from colorectal cancer. Radiation therapy is useful as a palliative local treatment for painful bone metastases or compressive nodes. Chemotherapy, still palliative, has been shown to improve the quality of life. Although 5-fluorouracil remains the drug of reference, various routes and schedules of administration (continuous infusion, hepatic artery infusion, chronotherapy) and biomodulation, mainly by folinic acid and methotrexate have led to a significant improvement in response rates. PMID- 7878366 TI - [Diuretics. Principles and rules of use]. PMID- 7878367 TI - [Placement requested by a 3rd party and mandatory placement. Guardianship, trusteeship, legal protection. Principles of application and principles of use]. PMID- 7878368 TI - [Therapeutic trials, informed consent. Methodological bases, legal and ethical aspects]. PMID- 7878369 TI - [Influenza. Epidemiology, etiology, physiopathology, diagnosis, treatment, prevention]. PMID- 7878370 TI - [Smoking. Epidemiology and pathology related to tobacco]. PMID- 7878371 TI - [Transient cerebrovascular accidents. Epidemiology, etiology, physiopathology, diagnosis, course, prognosis, treatment]. PMID- 7878372 TI - Effects of signal-to-noise ratio on the auditory brainstem response to 0.5 and 2 kHz tone bursts in broadband noise and highpass noise or notch noise. AB - This study investigated the effects of signal-to-noise ratio (S/N) on the latency and amplitude of th3 auditory brainstem response (Wave V) using 0.5 and 2 kHz tone bursts in highpass/notch noise and broadband noise. Normal listeners were presented with 40 and 80 dB nHL tone bursts in quiet and in noise at S/Ns of 10, 15, 20, and 25 dB. The latency data suggest that, at moderate and high intensities, highpass/notch noise or broadband noise is preferred to the quiet condition because of the improved frequency specificity provided by the masking. Highpass/notch noise appears preferable to broadband noise when testing at moderate to high levels because the former produced larger Wave V amplitudes to 0.5 and 2 kHz tone bursts at 80 dB nHL. The 80 dB nHL data also suggest that S/Ns of 15-25 dB should be selected when the highpass/notch noise is mixed with moderate to high level 0.5 and 2 kHz tone bursts. In contrast to the 80 dB nHL data, Wave V amplitudes to the 40 dB nHL tone bursts suggest that testing in quiet may be preferred to testing in noise when 0.5 and 2 kHz tone bursts are presented at low levels. This is because of the simplicity of instrumentation and because larger amplitudes were observed in quiet than in noise. PMID- 7878373 TI - Technical aspects of recording evoked otoacoustic emissions using maximum length sequences. AB - Our previous work has demonstrated the feasibility of recording evoked otoacoustic emissions (EOAEs) using maximum length sequence (MLS) techniques. New equipment has been constructed, using standard DSP boards and computers, which permits stimulation at much higher rates. The technical aspects of analogue-to digital converter (ADC) requirements, stimulus problems, artefacts, signal-to noise ratio (SNR) computations and MLS application are considered here and illustrated with data from the new system. PMID- 7878374 TI - Hearing impairment in Oslo born children 1989-91. Incidence, etiology and diagnostic delay. AB - An investigation of incidence, etiology and diagnostic delay was performed in Oslo born children referred to the audiological department of Ulleval Hospital in the period 1989-91; hearing loss in these children required amplification and audiopedagogical training. An increase in incidence compared with 1975-84 was found. No child had a hearing loss caused by rubella. The age at time of diagnosis is increased, with a median age of 28 months. Children with moderate hearing losses are diagnosed at later ages. A considerable delay in the diagnosis of hearing-impaired children is shown. PMID- 7878375 TI - Performance of normally hearing and hearing-impaired listeners using a German version of the SPIN test. AB - Various stages in the development of a German version of the English SPIN (Speech Performance in Noise) test have been reported previously by the authors (Zust & Tschopp, 1993). The test forms consist of 15 sentences each with a length of five to nine syllables. The forms have been constructed with either low predictable (LP) final words or high predictable (HP) final words, based upon the amount of contextual information available in the sentence. The test is performed with a background noise and uses adaptive testing strategies. The proportion of HP to LP responses is compared. Normally, scores of the HP segment are higher than those of the LP segment of the test, because the increased contextual information contributes to a better understanding of the HP final words. The SPIN test results in young normally hearing listeners (n = 12), elderly normally hearing listeners (n = 13), young hearing-impaired subjects (n = 14) and elderly hearing impaired subjects (n = 19) are reported. The most important findings were that the LP-HP difference was not dependent on the degree of peripheral hearing loss, and that no age-related effects could be demonstrated. The SPIN test results were compared with conventional speech audiometric parameters, hearing threshold levels for pure tones and self-reported hearing handicap. Low to moderate correlations were present but were not consistent across comparisons. PMID- 7878376 TI - Behavioral counselling for subjects with acquired hearing loss. A new approach to hearing tactics. AB - Effects of behavioral counselling of subjects with an acquired hearing loss were evaluated in an experimental design. The study included a group of 20 hearing impaired subjects who were assessed and randomly allocated to a treatment or control group. Behavioural counselling, individualized according to the results of functional analysis, was then given to 10 subjects and included the teaching of 'hearing tactics'. The groups were measured three times, pre-counselling and post-counselling and at a 15-month follow-up, after which treatment results were analysed. Significant (time x treatment) interactions were followed by post-hoc testing revealing that the treated group had improved in several areas of functioning while controls had not. These results were in agreement with interview data. The findings indicate that a behavioural counselling approach to hearing tactics is beneficial in the understanding and rehabilitation of hearing loss, especially over time. PMID- 7878377 TI - The effect of pre-fitting counselling on the outcome of hearing aid fittings. AB - The effect of pre-fitting counselling on the outcome of fittings of NHS behind the-ear hearing aids to adult first-time users was investigated. Questionnaires and diaries were sent both before and after fitting to 48 subjects who were given pre-fitting counselling and 47 control subjects, all of whom were fitted with standard NHS hearing aids in Southampton or Bath between September 1989 and July 1991. The test and control groups had similar distributions of age, sex and hearing loss. Analysis of the data showed that the counselling had no significant effect on levels of satisfaction, aid usage or benefit; these outcome measures also showed no significant correlation with any of the personal characteristics or attitude factors which were studied. PMID- 7878379 TI - International Enuresis Research Center (IERC) 1st International workshop. Proceedings. 22-24 October 1993. PMID- 7878378 TI - Comparative study of the usefulness of play-conditioned audiometry with wooden rings and electronic video peep show. Audiometric testing of children at the age of two years. AB - This study was conducted to investigate the effect of new technology in play conditioned audiometry. The aim was to evaluate whether reinforcement equipment consisting of an electronic video peep show is more advantageous than conventional techniques using coloured wooden rings resulting in a lowering of the age for application of audiometry in children. Thirty-one healthy two-year old children (18 boys and 13 girls) were tested at the standard audiometric frequencies from 125 to 8000 Hz using both techniques. Fifteen were tested using the wooden ring methods as the first test, and 16 were examined starting with the video peep show. A median of three thresholds (range 0-11 thresholds) was measured using the conventional technique compared to zero thresholds (range 0 11) with the video peep show. Twenty-seven of the tested children were able to establish reliable thresholds. The study did not demonstrate any advantage for determining thresholds using video peep show in comparison with the traditional wooden ring method in tested group of children at two years of age. PMID- 7878381 TI - Nocturnal enuresis: social aspects and treatment perspectives in Italy--a preliminary report. PMID- 7878382 TI - Nocturnal enuresis: social aspects and treatment perspectives in Japan. PMID- 7878383 TI - Children's notions about enuresis and the implications for treatment. AB - Children with nocturnal enuresis (n = 50) completed a range of measures designed to elicit their attitudes and perceptions regarding the problem prior to any treatment intervention. The measures included belief over aetiology, perceived impact on lifestyle, self image, estimates of parental tolerance and implications of becoming dry. Treatment consisted of the body worn enuresis alarm (9), with children followed up for 16 weeks. Child measures were related to outcome measures and a model linking presence of implications, negative self image and belief in incomplete learning of bladder control emerged as important predictors of treatment outcome. The implications of this result are discussed with reference to the clinical context. PMID- 7878384 TI - Nocturnal enuresis--a burden on family economy? PMID- 7878380 TI - Nocturnal enuresis: social aspects and treatment perspectives in France. PMID- 7878385 TI - Nocturnal enuresis--is there a rationale for treatment? PMID- 7878386 TI - Longitudinal study of urinary symptoms in children. Longitudinal study of urinary symptoms and incontinence in local schoolchildren. PMID- 7878387 TI - Comments on enuresis, particularly the nocturnal type. PMID- 7878388 TI - On the epidemiology of nocturnal enuresis--a critical review of methods used in descriptive epidemiological studies on nocturnal enuresis. PMID- 7878389 TI - On the epidemiology of nocturnal enuresis--a selected bibliography from a social science perspective. PMID- 7878390 TI - Pulsatile release of arginine vasopressin (AVP) and it's effect on response to desmopressin in enuresis. AB - A response to desmopressin spray is only seen in a proportion of children with enuresis. To investigate whether response is related to nocturnal levels of arginine vasopressin (AVP) 35 children with enuresis, aged 8 to 14 years, had plasma AVP measurements overnight before entering a double blind randomised, placebo controlled crossover study to assess their response to evening treatment with desmopressin spray. There was no significant difference seen between nocturnal AVP levels obtained from children who responded to desmopressin and those who did not. Frequent sampling in six children demonstrated a pulsatile pattern of secretion for AVP. This has implications for studies of nocturnal AVP levels, and questions the validity of using infrequent measurements of AVP to assess it's secretion. PMID- 7878391 TI - Mesh-glove. 1. A method for whole-hand electrical stimulation in upper motor neuron dysfunction. AB - A newly devised method for electrical stimulation via a wired mesh-glove is described. The stimulation paradigm is novel in that a whole hand is the target of stimulation. Specific standardized stimulation modalities are reviewed. The protocol for mesh-glove stimulation for patients with and without volitional movements, but increased muscle tone is outlined. A sequenced program based on restoration of motor functions is described. The mesh-glove stimulation is well suited for home use. On the basis of our experience working with 40 patients after stroke, head and spinal cord injuries, we concluded that this procedure is beneficial and safe. PMID- 7878392 TI - Mesh-glove. 2. Modulation of residual upper limb motor control after stroke with whole-hand electric stimulation. AB - The effects of whole-hand electrical stimulation via a wired mesh-glove upon the residual motor control of the upper extremity are described. Clinical observations were made in 2 patients with nonfunctional upper limbs, 4 and 2 years after stroke, who had been enrolled in the home mesh-glove program for 6 and 4 months, respectively. The stimulation paradigm is novel and the target of stimulation is the hand. Preliminary results indicate beneficial effects such as reduction in muscle hypertonia and facilitation of isolated hand movements. PMID- 7878393 TI - Efficacy of botulinum toxin for cervical dystonia. A comparison of methods for evaluation. AB - Twenty patients with cervical dystonia were treated during one year with repeated intramuscular injections of botulinum toxin. The outcome was evaluated comparing subjective global rating with relative changes in degree of pain on the Visual analogue scale (VAS), degree of dysfunction due to dystonia, and quality of life according to the Nottingham health profile (NHP). Objective measurement of dystonic position and movement ability was performed using a goniometer, semiquantitatively noted as scores according to Fahn and Tsui. Before treatment, the degree of impaired life quality on the NHP did not correlate with the Tsui score of dystonic posture, but significantly with the Fahn score (p < 0.01) which also includes data on pain. Significant improvement after treatment was seen for all parameters (p < 0.05). Global subjective rating correlated significantly with improved posture according to the Tsui score (p < 0.05), but not with reduced pain or degree of dysfunction. The results suggest that the efficacy of botulinum toxin in cervical dystonia is best evaluated using a combination of the VAS for pain and the Tsui score for dystonic posture and movement ability. PMID- 7878394 TI - Early modifications of biochemical markers of bone metabolism in spinal cord injury patients. A preliminary study. AB - Spinal cord injury is associated with the development of a rapid and severe osteoporosis which might reflect uncoupling between bone formation and resorption. A prospective study was made in 6 spinal cord injury patients followed up to 2-3 months after onset with various markers of a) bone formation: osteocalcin and C-terminal peptide of type I procollagen, b) bone resorption: pyridinolines and C-terminal telopeptide of type I collagen, c) connective tissue metabolism: amino-terminal propeptide of type III collagen (PIIINP). Preliminary results show that early after onset, bone formation was depressed as compared to dramatically increased bone resorption. Low bone formation rate lasted two weeks before it began to raise, while bone resorption showed a continuous tendency to increase. The dramatic increase in PIIINP levels might represent some attempt of bone to repair. This paper describes the evolution of various biochemical markers of bone and connective tissue metabolism after onset of paralysis and critically reviews the use of those markers in patients with spinal cord injury. PMID- 7878395 TI - Measurement of pain among electricians with neck dysfunction. AB - The aim of the study was to develop a pain measurement instrument in Swedish intended for use in epidemiological surveys, and to report the pain assessments of individuals in a working population. The focus was on somato-sensory description in relation to work performance. The material comprised 22 randomly selected electricians attending health checkups, and reporting neck pain during the past week. The pain estimations were made in oral interviews using a specially developed questionnaire. Neck extension and hands above shoulder height caused increased neck pain in all the subjects. The quantitative assessments of present pain showed a limited intensity. To describe the pain quality a wide spectrum of words was used as pain descriptors, but five adjectives were preferred. The more the pain was spread on the pain drawing, the more differentiated was the assessment of its quality. The results concluded that the pain assessment instrument might be useful in epidemiological investigations of musculoskeletal neck dysfunctions. PMID- 7878396 TI - Non-dynamometric trunk performance tests: reliability and normative data. AB - A sample of 508 male and female white-collar and blue-collar employees aged 35 to 54 years was evaluated clinically to determine the reliability of repetitive sit ups, repetitive arch-ups, repetitive squatting, and static back endurance tests, to determine the normal values of these tests and to detect determinants for trunk muscle performance. All of the given tests had fairly good or even excellent test-retest reliability. Muscular performance capacity decreased with advancing age, particularly among blue-collar workers. Men showed greater muscle endurance in all the muscle tests, and blue-collar workers lower values in all tests. The repetitive tests, in particular, showed reduced values in those with previous low-back pain. Normative values of back endurance, repetitive squatting, sit-up and arch-up tests for different age, sex and occupational groups are presented. PMID- 7878397 TI - The gait of unilateral transfemoral amputees. AB - The aim of this study was to describe the gait of persons with a unilateral transfemoral amputation by means of a questionnaire, gait analysis and measurement of energy expenditure, and to find correlations among the variables studied. The study included 29 transfemoral amputees amputated for other reasons than a chronic vascular disease. The patients were assessed using the following methods: 1) A questionnaire rating the walking distance and walking difficulty in different circumstances. 2) Gait analysis measuring temporal variables and goniometry of hips and knees. 3) Measurement of energy expenditure during sitting and walking. Scores on the questionnaire showed a correlation with socket design, a negative correlation with age and energy expenditure, and a positive correlation with fast speed. The gait of transfemoral amputees was asymmetrical as far as temporal variables were concerned, and for most amputees also for the range of motion of hip and knee. The walking speed of the amputees was lower than that of non-amputees and showed a positive correlation with hip extension-flexion range of motion and a negative correlation with age and stride time. The energy expenditure of the amputees during ambulation was higher than that of non amputees, and seemed to correlate with residual limb length and the hip abduction adduction range of motion. PMID- 7878398 TI - [Ductal carcinoma in situ of the breast]. AB - With the advent of screening mammography, ductal carcinoma in situ (DCIS) is detected with increasing frequency and now accounts for 10-15% of all diagnosed breast cancers. Before 1980, DCIS was usually diagnosed by clinical findings of a breast mass or nipple discharge; today most cases are detected mammographically and nonpalpable. The most common mammographic findings associated with DCIS are a cluster of microcalcifications. The concept that DCIS invariably progresses to invasive breast cancer and requires mastectomy has been challenged. Knowledge of DCIS is limited and primarily based on retrospective data. Further insight will emerge from ongoing randomized prospective studies that are near completion. Currently available data indicate that breast-conserving modalities may offer a valid alternative to mastectomy in selected patients with DCIS. PMID- 7878399 TI - [Megaloblastic anemia: 30 cases in a district hospital]. AB - The high incidence of megaloblastic anemia observed at our institution (2.1% of hospital admissions) prompted us to analyze the causes of cobalamin and/or folate deficiency in 30 patients admitted during the period 1983-1991 to the Medical Department of Locarno District Hospital. The study population includes 19 women and 11 men with a mean age of 69 years (range 28-91 years). All patients had severe macrocytic anemia (mean hemoglobin 74 +/- 23 g/l, MCV 121 +/- 12 fl), striking megaloblastic changes in aspirated marrow, and an elevated serum level of LDH (2170 +/- 2150 U/l). 19 patients had associated thrombocytopenia, 12 leukopenia and 11 both thrombocytopenia and leukopenia. Treatment led to prompt reticulocytosis and correction of megaloblastic changes in all patients, as well as to nearly complete resolution of the neurologic disorder in a patient with severe spastic ataxia. In 15 patients, megaloblastic anemia was caused by folate deficiency related to alcoholism (n = 6, mean age 55 years) and old age or poverty (n = 9, mean age 73 years). Cobalamin deficiency was present in 9 patients (mean age 69 years); it was due to pernicious anemia in 6 patients and to malabsorption in 2, while the cause remained unexplained in 1. The last patients (mean age 76 years) had deficiency of both cobalamin and folate, related to alcoholism (n = 3) or poverty (n = 3). PMID- 7878400 TI - [Diagnostic value of C-reactive protein in comparison with erythrocyte sedimentation as routine admission diagnostic test]. AB - In a prospective study the diagnostic relevance of C-reactive protein (CRP) as a screening parameter for inflammatory diseases was compared to the erythrocyte sedimentation rate (ESR). At time of hospitalization CRP, ESR and other routine laboratory tests were performed. After taking history and clinical examination, the responsible physician had to answer a first questionnaire and a second at the time of patient discharge. At the time of admission, elevation of CRP was expected by the treating physician in 40.3% of patients, and elevation of ESR in 43.2%. An unexpected elevation of CRP or ESR was found in 38/303 cases (12.5%). In 22/38 patients only CRP was elevated, but ESR only was elevated in 13/38 cases. In summary, measurement of CRP and/or ESR was felt by the treating physician to have been helpful in 25.1% of all patients. Due to the fast rise of CRP, all patients with bacterial pneumonia showed increased CRP at the time of hospitalization (23/23), but the ESR was still in normal range in some of these patients (normal ESR in 5/23). Also in patients with COPD or asthma and clinical evidence for infection, or patients with bacterial gastroenteritis, CRP turned out to be the more sensitive parameter. In conclusion, CRP is a valuable screening test in acutely ill patients, has a higher sensitivity and (as shown by other authors) higher specificity than ESR. In addition, the short half-life of CRP makes it a useful parameter for the follow-up of patients with e.g. infections under antibiotic treatment. PMID- 7878401 TI - [Vigabatrin and lamotrigin: experiences with 2 new anticonvulsants in the Swiss epilepsy clinic]. AB - Vigabatrin and lamotrigine are two new antiepileptic drugs which have recently become available. Vigabatrin is a specific and irreversible inhibitor of the enzyme gamma-amino-butyric-acid (GABA) transferase. Its administration leads to a long lasting increase in GABA, the most important inhibitory neurotransmitter. Vigabatrin is effective in both adults and children in the treatment of partial and especially complex-partial seizures. After add-on in vigabatrin to their therapeutic drug regime in 116 of our own patients, 39% of previously therapy resistant patients reported a reduced seizure frequency of at least 50% and 6% of them became seizure free. In secondarily generalized epilepsies the best results were observed in axial (infantile) spasms. In addition there was some improvement in tonic and convulsive seizures. Single patients showed increased myoclonic and clonic seizures. Initial efficacy was not always maintained during follow-up. In the experience of other authors, vigabatrin is also effective in the treatment of infantile spasms. It is not suitable for the treatment of generalized epilepsies with absences and myoclonic seizures. Most patients tolerate vigabatrin very well, although psychotic episodes are sometimes reported. So far there have been no relevant hepatic or hematological side effects. Lamotrigine is also effective in the treatment of partial seizures, for which it is approved. However, uncontrolled studies and our own experience have shown that it is even more effective in generalized seizures. As add-on therapy in absences and tonic or tonic-clonic seizures, a significant reduction in seizure frequency--in individual cases seizure freedom--can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878402 TI - [Heart interventions in Switzerland 1992. PTCA and Fibrinolysis Study Group of the Swiss Society of Cardiology]. PMID- 7878404 TI - Should physicians intervene during childhood to prevent adult hypertension? AB - Hypertension in adulthood is a major health problem, and drug treatment of hypertension is expensive and has adverse side effects. By the time that treatment of hypertension begins during adulthood, considerable damage may have already been done to the arterial system, to the left ventricle, and perhaps to other organs. Thus, from several points of view, prevention would be preferable to treatment. We can consider both the high-risk approach and the population approach during childhood for the prevention of adult hypertension. In the high risk approach, we must first identify individual children who are at high risk and then intervene among them on a one-on-one basis. Identifying the future hypertensive is difficult because of large day-to-day variability in blood pressure during childhood, poor tracking of blood pressure from childhood to adulthood, and the current lack of good gene markers for hypertension. With the population approach, we do not need to identify high-risk children, but take steps among all children that will help prevent the development of hypertension in the entire population. At the present time, our best approach for the prevention of adult hypertension seems to be the population approach. We should make the usual diet, for all children, lower in sodium and fat and higher in potassium and calcium. This is effected by increasing their intake of vegetables, fruits, and whole grains, which should become the basis of the diet, rather than high-fat meat and dairy products. Further, increasing strenuous physical activity in our children may help prevent the development of obesity. Finally, preventing the initiation of cigarette smoking and excess alcohol consumption will help in our efforts to prevent hypertension and its sequelae in the next generation of adults. PMID- 7878406 TI - [Noninvasive assessment of morphology and function of the great vessels]. AB - Hypertension is well recognized as a risk factor that is associated with an increased incidence of stroke and myocardial infarction. The early detection of atherosclerosis is a real challenge and should be carried on at a cost and with a degree of risk and invasiveness that does not preclude its use in subjects with cardiovascular risk factors. For this purpose we have developed a non-invasive approach using a high resolution echotracking device making it possible to measure internal diameter and wall thickness of conduit arteries as well as their biomechanical properties. We present here a methodological overview of the system with a brief clinical study addressing the biomechanical properties of a medium size artery in hypertension as compared with normotension. PMID- 7878403 TI - [Hypercholesterolemia in children and young adults: should screening be done?]. AB - Risk factors such as hypercholesterolemia, hypertension and smoking are already operative in children and during adolescence; it has been demonstrated that they favour the development of early atherosclerosis lesions in young adults. This fact poses the question of diagnosis and treatment of risk factors. There is still controversy whether hypercholesterolemia should be searched for by universal or by selective screening, or by no screening at all. Several professional organizations favour a selective screening strategy, i.e. determination of serum cholesterol if one parent has premature coronary heart disease (before age 55 yr) or if the family has familial hyperlipidemia, in particular familial hypercholesterolemia. This strategy is advocated here: cholesterol should be measured early, i.e. between age 6 and 8 yr. A total serum cholesterol of > 5.2 mmol/l is elevated (approx. 75th percentile) and should be further evaluated and possibly treated. The presence of familial hypercholesterolemia should be looked for in particular: such individuals can now be diagnosed with molecular genetic tools, and they are particularly prone to develop premature coronary heart disease. Treatment of hypercholesterolemia is mainly of a dietary nature, or possible with a bile acid binding resin (cholestyramine). Other drugs have not been sufficiently evaluated for efficacy and safety; they may be indicated in special cases such as patients with a very high risk. Young people with familial hypercholesterolemia should be particularly counselled to avoid other risk factors such as smoking. PMID- 7878405 TI - [Hypertension and vascular diseases: molecular and cellular mechanisms]. AB - Increased blood pressure can be observed in about 15-20% of the Swiss population. Hypertension causes few or no symptoms, but is an important risk factor for myocardial infarction, stroke, renal failure and peripheral vascular disease. All these clinical complications of hypertension are preceded by functional changes of blood vessels and the myocardium (left ventricular hypertrophy). In conduit arteries, hypertension is associated with atherosclerotic changes, while in resistance arteries only increased medial thickness can be observed. In atherosclerosis, functional changes of the endothelium, vascular smooth muscle, platelets and monocytes occur. These changes lead to hypercontractility, increased interaction of circulating blood cells with the blood vessel wall, and to proliferation and migration of vascular smooth muscle cells. These events impair local blood flow and eventually may cause vascular occlusion. The endothelium plays a particularly important role as a regulator of these mechanisms. Accordingly, it is likely that an endothelial dysfunction occurs at the very beginning of the atherosclerotic process. In resistance arteries, remodeling of vascular smooth muscle cells leads to thickening of the media with encroachment on the lumen due to an increased media lumen ratio. These hypertension-induced vascular changes are in part reversible by antihypertensive drugs. Hypertension-induced vascular disease is preceded by numerous alterations in the expression, secretion and action of mediators and receptors of endothelial cells, vascular smooth muscle, platelets and monocytes. It is hoped that increased understanding of the cellular/molecular mechanisms of hypertensive vascular disease will allow more effective therapy (and in the future also gene therapy) as well as better prevention of coronary artery disease in hypertensive patients. PMID- 7878407 TI - [Physiopathology of cardiac insufficiency. Biological factors of adaptation and disadaptation of the heart to chronic mechanical overload]. AB - The advent of molecular biology techniques has profoundly changed pathophysiological concepts of myocardial hypertrophy and overload-induced heart failure. Heart failure is a consequence of the limits and imperfection of biological adaptation to mechanical overload. Factors including fibrosis, senescence, ischemia, inflammation, catabolism and hormonal response may contribute to myocardial dysfunction. In humans changes in the genes coding for myosin are observed only in the atrial myocardium, in association with diastolic left ventricular function. In most animal species, alteration in proteins involved in intracellular calcium movement and autonomic nervous dysfunction are responsible for both reduction of Vmax and arrhythmias associated with myocardial hypertrophy. Moreover, myocardial fibrosis is a major determinant of enhanced left ventricular stiffness and arrhythmogenicity. PMID- 7878408 TI - [Fetal cardiac disorders]. AB - Thanks to recent developments in ultrasonography, morphological and functional studies of the fetal heart have become very reliable. The acquired experience of recent years now allows routine surveillance of the fetal heart in pregnancies at risk, especially when family, fetal or maternal indications exist. The best time for a detailed echocardiographic examination is between the 18th and 22nd week of gestation, which leaves time for a other investigations that may be warranted before critical decisions have to be taken. Fetal cardiology today is not restricted to the diagnosis of structural cardiac malformations only, but allows the identification of arrhythmias and, if necessary, their treatment. Our experience is compared with that of major centres. Ongoing research offers hope that new therapeutic methods will be developed that may prevent or cure fetal cardiac diseases. PMID- 7878409 TI - [Acquired heart diseases and pregnancy]. AB - Understanding of the mechanisms of cardiovascular and hemodynamic adaptation during pregnancy helps to prevent or manage complications in cardiac patients during gestation. Manifestations of coronary heart disease are exceptional during pregnancy and delivery. The same is true of disorders of the pericardium. Peripartal cardiomyopathy is a myocardial disorder of undetermined cause occurring shortly before, during or after delivery, which may take a fatal course. Hypertrophic obstructive or non-obstructive cardiomyopathy is compatible with gestation and delivery without serious complications in most cases. Rheumatic mitral stenosis was the most common cardiac disorder until the 1950s. Nowadays it is rarely seen in this country. Surgical and other interventional therapies have greatly changed the outlook in pregnant women with valvular heart disease. A highly controversial issue is heart valve replacement in young women and management of anticoagulation during pregnancy. Like any other drug therapy, anticoagulation during gestation requires careful weighing of the benefit for the mother against toxic and teratogenic effects for the fetus. In women with heart disease the management of pregnancy should start, if possible, before conception. Thorough counseling and proper planning of pregnancy and of therapeutic measures is essential in order to avoid or manage complications. PMID- 7878410 TI - Pregnancy in patients with congenital heart disease. AB - Pregnancy and delivery in women with congenital heart disease remain inadvisable for patients at high risk due to the following congenital diseases: (1.) Severe left ventricular outflow tract obstruction (increase of pressure gradient); (2.) Eisenmenger syndrome (increase of right to left shunt with worsening of cyanosis and fetal growth retardation); (3.) Marfan syndrome with enlarged aortic root (risk of aortic dissection). In women suffering from cyanotic congenital heart disease the main risk is fetal complications. These are correlated to oxygen saturation and to the type of maternal disease, particularly if a palliative shunt operation has never been performed. Women with left to right shunt, right outflow tract obstruction or previous correction of the disease can go through pregnancy with low risk of mortality. The complications (mainly heart failure and arrhythmias) can be well managed with medical treatment, and the fetal outcome is similar to that in the general population. PMID- 7878411 TI - [Pregnancy and heart disease from the obstetrician's viewpoint]. AB - Successful termination of pregnancy is a major challenge requiring close collaboration between obstetrician, cardiologist, anesthesiologist, intensive care specialist and pediatrician. This article summarizes some aspects from the obstetrician's point of view. PMID- 7878413 TI - [Oral health--affordable for all?]. PMID- 7878412 TI - [Scientific raisins from 125 years of SMW. Transition forms between mental disorders and mental health. Constitutional psychopathies or disorders of character formation, with special reference to perverse inclinations. Laws and measures against such abnormalities of brain function. Paper presented at the 1889 Fall meeting of the Physicians' Association of Canton Zurich. 1889]. PMID- 7878414 TI - [Costly prevention...]. PMID- 7878415 TI - [Subgingival plaque due to gingivitis and inactive periodontitis sites in the adult periodontitis patient]. AB - There are several discrepancies with respect to the composition of subgingival plaque in gingivitis and in inactive adult periodontitis (AP). In this study we compared subgingival plaque samples taken from gingivitis sites to those from inactive periodontitis sites of the same patients. Of 44 patients plaque samples from 86 gingivitis sites and 92 periodontitis sites were analysed. Darkfield microscopy showed a higher proportion of spirochetes and mobile rods in the periodontitis sites. Analysis of cultures revealed a higher and statistically significant number of anaerobes in the periodontitis sites (1.7 x 10(7) vs 3 x 10(6), p = 0.006). The following bacterial species were isolated more frequently from periodontitis sites than from gingivitis sites: Actinobacillus actinomycetemcomitans (18% vs 10%), as well as the black-pigmented Prevotella intermedia (68% vs 48%) and Porphyromonas gingivalis (48% vs 28%). On the one hand, these small differences in the bacteriological parameters can be explained by the fact that both gingivitis and periodontitis plaque samples were taken from the same periodontitis patients. An infection of the gingivitis sites from the parodontitis sites within the same patient could not be excluded. On the other hand, the mean probing depth of the gingivitis sites was relatively high, 3.6 mm (measuring point interdental plus pseudo-pocket) which may favor the growth of anaerobic bacteria. PMID- 7878416 TI - [The resistance spectrum and antibiotic therapy in progressive infections in the mouth, jaw and face areas]. AB - Assessing the surgically treated progressive abscesses of the head and neck from 1991 to 1993 at our clinic of maxillofacial surgery, a surprising percentage of the microbiologically isolated germs showed resistance against the recommended antibiotics of first choice. The location of the abscesses, the microbiological spectrum and the clinical course are analysed and compared with the literature. Preventing possible severe complication of progressive abscesses of the head and the neck an additional parenteral antibiotic therapy in high doses combined with the surgical treatment is recommended. Common dentoalveolar infections without progressive tendency are sufficiently treated surgically without administration of antibiotics. PMID- 7878419 TI - [Dental hygiene in the awareness of the Swiss population. A representative survey of 2400 households with 4537 persons in German- and French-speaking Switzerland]. PMID- 7878418 TI - [The oral health status of emergency dental patients in Austria]. AB - It is often suggested that people who require emergency dental treatment are mainly those who do not care about their teeth and do not have regular visits to their dentist. Little is known about their dental health. Therefore a study was initiated to get more information on the oral health state of these people. The dental care for these patients could be improved selectively in future. 1214 patients using the emergency dental service at the University Clinic for Dentistry in Innsbruck/Austria where examined. More than 40% of these patients had untreated dental caries. Remnants of teeth, as the result of carious destruction, were found in 13.3% of these people. The (dt+DT) value was 2.4 at the age 3-12 years. 6.5 teeth on average were missing at the age 35-44 and about 40% of these patients did not wear a dental appliance for replacement of missing teeth. The emergency dental service was used most frequently by people aged 25 to 35 years. It can be assumed that especially this age-group does not care enough about their teeth. Therefore an effective dental health service including these people as well as some certain profession-groups which were found in this study to stand out by reduced oral health could improve the oral health by economically justifiable costs. PMID- 7878417 TI - Sonic and ultrasonic scalers in a clinical comparison. A study in non-instructed patients with gingivitis or slight adult periodontitis. AB - In the present study, the Cavitron 2002 ultrasonic scaler was compared with the Titan-S air scaler in 20 subjects with gingivitis or slight periodontitis, whereby the majority of the patients suffered from gingivitis. A split mouth experimental design was used. However, patients did not receive any oral hygiene instructions during the study in order to allow the observation of the true effect of instrumentation. The outcome of a one-time treatment was assessed after 4, 14, 28, and 56 days. Gingival crevicular fluid (GCF), papilla bleeding index (PBI), plaque index (Pl-I), probing depth (PD), and relative attachment level (AL) were measured. Both treatments resulted in a statistically significant decrease of clinical signs of inflammation (PBI: p < 0.001). Probing depths decreased (p < 0.001) and a small gain of attachment of 0.11 mm +/- 0.05 mm (p < 0.001) was observed. Following treatment, a statistically significant (p < 0.001) decrease in GCF and Pl-I was observed between baseline and day 4. No statistically significant difference between the instruments' influences on the evaluated clinical parameters could be found. Thus it can be concluded indirectly that the Cavitron 2002 and the Titan-S are both useful instruments for scaling of tooth and root surfaces. PMID- 7878420 TI - [Dental hygiene from the viewpoint of dental hygiene patients. A survey of 1700 patients cared for by dental hygienists for at least 2 years]. PMID- 7878422 TI - [Endodontics and restoration of the severely disordered pediatric dentition. A report on the joint meeting of the Society for Pediatric Dentistry and Primary Prophylaxis in the German Society for Dentistry, Oral Medicine and Orthodontics and the German Society for Pediatric Dentistry, Inc. of 14-15 October 1994 in Gottingen, Germany]. PMID- 7878421 TI - [The ionomer furcation implant. A new approach to the treatment of molar furcation defects]. PMID- 7878423 TI - [The maxillary implant. A report on the 3rd Conference of the Association for Oral Surgery and Implantology of the Austrian Society for Dentistry, Oral Medicine and Orthodontics. This meeting took place in Salzburg from 5 to 8 October 1994]. PMID- 7878424 TI - [Digital imaging. A report on the 3rd Symposium on Digital Imaging in Dental Radiology of 13-15 October 1994 in Noordwijkerhout, the Netherlands]. PMID- 7878425 TI - [The choice of treatment in traumatism of the anterior teeth. A report on the 5th World Congress of the IADT (International Association of Dental Trauma)]. PMID- 7878426 TI - [Prevention--the results and consequences for practice. A report on the continuing education course of the Clinic for Preventive Dentistry, Periodontology and Cariology of the Center for Dentistry, Oral Medicine and Orthodontics of the University of Zurich of 26 November 1994 in Zurich]. PMID- 7878427 TI - [The dental hygienist--a discriminating profession]. PMID- 7878428 TI - [Implant prosthodontics, foil technics, failures and their causes. A report on the 11th Annual Congress of the German Society for Implantology in Dentistry, Oral Medicine and Orthodontics, Inc. (DGI) in Baden-Baden from 16 to 19 November 1994]. PMID- 7878429 TI - [The administration of a dental practice]. PMID- 7878430 TI - [The founding of the Swiss Association for the Career Promotion of Dental Assistants (SVFZA)]. PMID- 7878431 TI - [Prophylaxis personnel: entrepreneurial kamikaze?]. PMID- 7878432 TI - [Some memoirs on study and work]. PMID- 7878433 TI - [Ca2+ and opiates]. PMID- 7878434 TI - [Mechanisms underlying effects of pressor and depressor areas in the brainstem]. PMID- 7878435 TI - [Role of ATP sensitive K(+)-channels in cardiovascular system]. PMID- 7878436 TI - [Membrane fusion and role of lipid polymorphism in it]. PMID- 7878437 TI - [Action of substantia nigra in pain modulation]. PMID- 7878438 TI - [Studies on a novel endogenous blood pressure regulator--antihypertensive factor]. PMID- 7878439 TI - [Modulatory effects of nicotine on muscarinic acetylcholine receptors and its molecular mechanisms]. PMID- 7878440 TI - [Spinal ganglions are true ganglions]. PMID- 7878441 TI - [N-methyl-D-aspartate-sensitive glutamate receptors and seizure]. PMID- 7878442 TI - [Mechanism of pineal transduction]. PMID- 7878443 TI - [Renin binding protein]. PMID- 7878444 TI - [The cytoskeleton absorptions and defences for mucosal epithelium of the small intestines]. PMID- 7878445 TI - Inter-individual variation of selenium in maternal plasma, cord plasma and placenta. AB - Selenium (Se) in high doses has been known to cause injury to the fetus and newborn. The major difficulty in assessing the effects of selenium on human reproduction stems from the need for a suitable means of estimating maternal and fetal exposure. The present investigation, therefore, examines the respective reliability of maternal plasma, cord plasma and placenta as epidemiological indicators as well as inter-individual variation of this trace element. An unselected population of 128 pregnancies was studied. Obstetrical characteristics were noted. Selenium concentrations were determined for maternal plasma, cord plasma, and placental tissue by fluorometric analysis. Maternal plasma selenium concentrations (Se-Bm) were significantly greater than fetal concentrations (Se Bc). Placental selenium (Se-Pl) levels were four times that of fetal levels. Variability of Se-Bc is best explained by placental concentrations. Maternal weight and ethnic origin are significantly correlated with Se-Bc. Female newborn have higher selenium levels than male newborn. The present study demonstrates the significance of the placenta as an indicator of fetal selenium exposure. PMID- 7878446 TI - The use of biomarkers for assessing the effects of organic pollution in mussels. AB - Wild mussels were collected from two stations with different pollution loads. Soft tissues were analyzed for their aromatic hydrocarbon and polychlorinated biphenyl content. Mixed function oxidase (MFO) system components and antioxidant defenses (catalase, superoxide dismutase and glutathione peroxidase) were determined in digestive gland microsomal and cytosolic fractions, respectively, and the magnitude of biochemical responses related with pollutant tissue levels. Results showed that significant differences existed in hydrocarbon content between mussels from the two stations, while a smaller difference in the biological response was detected. PMID- 7878447 TI - The analysis of lead, cadmium, zinc, copper and nickel content in human bones from the upper Silesian industrial district. AB - The concentration of lead, cadmium, zinc, copper and nickel in autopsy samples of bones from adults living in the Upper Silesian industrial district (Poland)--an ecological disaster region--was determined by atomic absorption spectrometry (flame and flameless GF AAS). Lead concentrations ranged from 20 micrograms/g to 200 micrograms/g bone wet weight, cadmium from 0.4 microgram/g to 1.5 micrograms/g bone wet weight. About one-fourth of the bones examined from Silesia, contained lead in the range from 100 micrograms/g to 200 micrograms/g. The were no significant differences in zinc, copper and nickel concentration between the control groups. The samples were mineralized in a microwave digestion system. To avoid anomalous results caused by the influence of the matrix Ca3 (PO4)2--the procedure of lead determination was carried out at a temperature of 2000 degrees C, the cadmium determination at a temperature of about 1200 degrees C. PMID- 7878448 TI - Human occupational radioactive contamination from the use of phosphated fertilizers. AB - 210Po and 210Pb concentrations in urine, hair and skin smear samples from individuals using phosphated fertilizers have been compared with a control group of occupationally unexposed individuals. Urine and hair samples of the test group showed slightly higher concentrations of 210Po and 210Pb than those observed for the control group. These concentrations remained, however, lower than those for uranium mine workers. Skin smear values indicated contamination by direct contact with dust from fertilizers and this may contribute to skin cancer induction in this risk population. PMID- 7878449 TI - Contamination of fish from different areas of the river Seine (France) by organic (PCB and pesticides) and metallic (Cd, Cr, Cu, Fe, Mn, Pb and Zn) micropollutants. AB - Organochlorine and metal pollution were studied in fish from different sites of the river Seine situated upstream and downstream of Paris. The metal content in roach were similar to those usually found in freshwater fish species. The PCB and the Pb pollutant levels in the fish evolved similarly along the river: from 1300 to 16,000 micrograms/kg dry weight for the PCBs and from 0.3 to 9.5 mg/kg for Pb, while the content of other metals did not change. The stations with the highest organochlorine contents are situated downstream from the Parisian discharges where there is a reduction of fish species present from 31 to 18. Fish caught at one station situated downstream from an industrial area (Guernes) contained a higher proportion of tri- and tetrachlorobiphenyls than fish from the other stations. Their muscle contents are above the French Food Standard of 2 ppm for PCB in fresh muscle. PMID- 7878450 TI - Longterm reduction of caesium concentration in milk after nuclear fallout. AB - Time trends in activity concentrations in milk as observed in Austria after the Chernobyl accident are presented. Both the short term decrease immediately after fallout and the medium term decline in the years following the event are very important for estimating the total exposure to be expected from a given deposition. In order to avoid artifacts due to local fallout, plant variations, or differences in the metabolism of single animals, large areas of production were used for the observations. This was achieved by observations of activity concentrations in milk powder, produced in large milk powder plants in Austria. After an initial decay with an approximate half-life of 34 days for the period of May to August 1986, a slower decrease in activity was observed during the following years. Observed half-lives are in the range of 1.5-2.0 a. Differences in the decrease observed between the different producing areas are discussed. The radiocesium contamination of milk and milk products depends directly on its presence in grass or hay and therefore, time trends observed in milk correspond closely to the time trend in these fodders. Other foodstuffs which are also produced on grass and hay, such as beef or lamb, should therefore display similar decay patterns, except for the early period after fallout when the biological half-lives in the animals influences the decrease. PMID- 7878451 TI - AIDS research policy. PMID- 7878452 TI - AIDS research policy. PMID- 7878453 TI - AIDS research policy. PMID- 7878454 TI - Biosphere 2. PMID- 7878455 TI - Oncogenes and cancer. PMID- 7878456 TI - A new phase in the war on cancer. PMID- 7878457 TI - Nobelists make a plea for NIH budget. PMID- 7878458 TI - Russian chaos breeds diphtheria outbreak. PMID- 7878459 TI - European Parliament axes patent policy. PMID- 7878460 TI - Did Darwin get it all right? PMID- 7878461 TI - Floyd Bloom: the next editor-in-chief of Science. PMID- 7878463 TI - Mechanisms and genes of cellular suicide. AB - Apoptosis is a morphologically distinct form of programmed cell death that plays a major role during development, homeostasis, and in many diseases including cancer, acquired immunodeficiency syndrome, and neurodegenerative disorders. Apoptosis occurs through the activation of a cell-intrinsic suicide program. The basic machinery to carry out apoptosis appears to be present in essentially all mammalian cells at all times, but the activation of the suicide program is regulated by many different signals that originate from both the intracellular and the extracellular milieu. Genetic studies in the nematode Caenorhabditis elegans and in the fruit fly Drosophila melanogaster have led to the isolation of genes that are specifically required for the induction of programmed cell death. At least some components of the apoptotic program have been conserved among worms, insects, and vertebrates. PMID- 7878462 TI - Targeting retroviral integration. PMID- 7878464 TI - Apoptosis in the pathogenesis and treatment of disease. AB - In multicellular organisms, homeostasis is maintained through a balance between cell proliferation and cell death. Although much is known about the control of cell proliferation, less is known about the control of cell death. Physiologic cell death occurs primarily through an evolutionarily conserved form of cell suicide termed apoptosis. The decision of a cell to undergo apoptosis can be influenced by a wide variety of regulatory stimuli. Recent evidence suggests that alterations in cell survival contribute to the pathogenesis of a number of human diseases, including cancer, viral infections, autoimmune diseases, neurodegenerative disorders, and AIDS (acquired immunodeficiency syndrome). Treatments designed to specifically alter the apoptotic threshold may have the potential to change the natural progression of some of these diseases. PMID- 7878465 TI - Structure of a hyperthermophilic tungstopterin enzyme, aldehyde ferredoxin oxidoreductase. AB - The crystal structure of the tungsten-containing aldehyde ferredoxin oxidoreductase (AOR) from Pyrococcus furiosus, a hyperthermophilic archaeon (formerly archaebacterium) that grows optimally at 100 degrees C, has been determined at 2.3 angstrom resolution by means of multiple isomorphous replacement and multiple crystal form averaging. AOR consists of two identical subunits, each containing an Fe4S4 cluster and a molybdopterin-based tungsten cofactor that is analogous to the molybdenum cofactor found in a large class of oxotransferases. Whereas the general features of the tungsten coordination in this cofactor were consistent with a previously proposed structure, each AOR subunit unexpectedly contained two molybdopterin molecules that coordinate a tungsten by a total of four sulfur ligands, and the pterin system was modified by an intramolecular cyclization that generated a three-ringed structure. In comparison to other proteins, the hyperthermophilic enzyme AOR has a relatively small solvent-exposed surface area, and a relatively large number of both ion pairs and buried atoms. These properties may contribute to the extreme thermostability of this enzyme. PMID- 7878466 TI - Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation. AB - I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-kappa B correlates with phosphorylation of I kappa B alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal induced phosphorylation or degradation, and NF-kappa B could not be activated. These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B. PMID- 7878467 TI - Requirement of RNA polymerase III transcription factors for in vitro position specific integration of a retroviruslike element. AB - The yeast retroviruslike element Ty3 inserts at the transcription initiation sites of genes transcribed by RNA polymerase III (Pol III). An in vitro integration assay was developed with the use of Ty3 viruslike particles and a modified SUP2 tyrosine transfer RNA (tRNA(Tyr)) gene target. Integration was position-specific and required Ty3 integrase, Pol III transcription factor (TF) IIIB-, TFIIIC-, and Pol III-containing fractions showed that TFIIIB and TFIIIC, together, were sufficient for position-specific Ty3 integration, but not for transcription. This report demonstrates that in vitro integration of a retroelement can be targeted by cellular proteins. PMID- 7878468 TI - Glutamate receptor RNA editing in vitro by enzymatic conversion of adenosine to inosine. AB - RNA encoding the B subunit of the alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptor (GluR-B) undergoes a posttranscriptional modification in which a genomically encoded adenosine is represented as a guanosine in the GluR-B complementary DNA. In vitro editing of GluR-B RNA transcripts with HeLa cell nuclear extracts was found to result from an activity that converts adenosine to inosine in regions of double stranded RNA by enzymatic base modification. This activity is consistent with that of a double-stranded RNA-specific adenosine deaminase previously described in Xenopus oocytes and widely distributed in mammalian tissues. PMID- 7878469 TI - Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 angstroms. AB - The p53 protein is a tetrameric transcription factor that plays a central role in the prevention of neoplastic transformation. Oligomerization appears to be essential for the tumor suppressing activity of p53 because oligomerization deficient p53 mutants cannot suppress the growth of carcinoma cell lines. The crystal structure of the tetramerization domain of p53 (residues 325 to 356) was determined at 1.7 angstrom resolution and refined to a crystallographic R factor of 19.2 percent. The monomer, which consists of a beta strand and an alpha helix, associates with a second monomer across an antiparallel beta sheet and an antiparallel helix-helix interface to form a dimer. Two of these dimers associate across a second and distinct parallel helix-helix interface to form the tetramer. PMID- 7878470 TI - Pineal opsin: a nonvisual opsin expressed in chick pineal. AB - Pineal opsin (P-opsin), an opsin from chick that is highly expressed in pineal but is not detectable in retina, was cloned by the polymerase chain reaction. It is likely that the P-opsin lineage diverged from the retinal opsins early in opsin evolution. The amino acid sequence of P-opsin is 42 to 46 percent identical to that of the retinal opsins. P-opsin is a seven-membrane spanning, G protein linked receptor with a Schiff-base lysine in the seventh membrane span and a Schiff-base counterion in the third membrane span. The primary sequence of P opsin suggests that it will be maximally sensitive to approximately 500-nanometer light and produce a slow and prolonged phototransduction response consistent with the nonvisual function of pineal photoreception. PMID- 7878471 TI - Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. AB - bcl-x is a member of the bcl-2 gene family, which may regulate programmed cell death. Mice were generated that lacked Bcl-x. The Bcl-x-deficient mice died around embryonic day 13. Extensive apoptotic cell death was evident in postmitotic immature neurons of the developing brain, spinal cord, and dorsal root ganglia. Hematopoietic cells in the liver were also apoptotic. Analyses of bcl-x double-knockout chimeric mice showed that the maturation of Bcl-x-deficient lymphocytes was diminished. The life-span of immature lymphocytes, but not mature lymphocytes, was shortened. Thus, Bcl-x functions to support the viability of immature cells during the development of the nervous and hematopoietic systems. PMID- 7878473 TI - Storage of 7 +/- 2 short-term memories in oscillatory subcycles. AB - Psychophysical measurements indicate that human subjects can store approximately seven short-term memories. Physiological studies suggest that short-term memories are stored by patterns of neuronal activity. Here it is shown that activity patterns associated with multiple memories can be stored in a single neural network that exhibits nested oscillations similar to those recorded from the brain. Each memory is stored in a different high-frequency ("40 hertz") subcycle of a low-frequency oscillation. Memory patterns repeat on each low-frequency (5 to 12 hertz) oscillation, a repetition that relies on activity-dependent changes in membrane excitability rather than reverberatory circuits. This work suggests that brain oscillations are a timing mechanism for controlling the serial processing of short-term memories. PMID- 7878472 TI - Synaptic desensitization of NMDA receptors by calcineurin. AB - Desensitization is a phenomenon that is common to many ligand-gated ion channels but has been demonstrated only rarely with physiological stimulation. Numerous studies describe desensitization of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor by exogenous agonists, but whether synaptic stimulation causes desensitization has been unknown. Synaptic stimulation of NMDA receptors on rat hippocampal neurons resulted in desensitization that was prevented by intracellular 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), adenosine-5'-O-(3-thiotriphosphate) (ATP-gamma-S), or inhibitors of phosphatase 2B (calcineurin), but not by inhibitors of phosphatases 1 and 2A or of tyrosine phosphatases. Synaptic NMDA receptors may fluctuate between phosphorylated and dephosphorylated forms, depending on the rate of synaptic stimulation and the magnitude of the associated influx of calcium through NMDA receptors. PMID- 7878474 TI - Interhelical angles in the solution structure of the oligomerization domain of p53: correction. PMID- 7878475 TI - Management of multiple myeloma. PMID- 7878476 TI - Autologous and allogeneic transplants for multiple myeloma. PMID- 7878477 TI - Cytokine, cytokine receptors, transduction signals, and oncogenes in human multiple myeloma. PMID- 7878479 TI - Treatment of primary amyloidosis. PMID- 7878480 TI - [Protective effect of calcitonin gene-related peptide on synaptic function in hippocampal slice during hypoxia]. AB - Rat hippocampal slices placed in two compartments of a dual chamber were immersed in the superfusing artificial cerebrospinal fluid (ACSF) with 95% O2 + 5% CO2. The population spike (PS) and presynaptic fiber volley (PV) were recorded in CA1 pyramidal cells by stimulating Schaffer collateral pathways. Following hypoxia produced by replacing O2 with N2, the PS became gradually diminished and abolished, and in parts of the slices hypoxic injury spikes (HIP) could be observed. When 4 nmol/L beta-calcitonin gene-related peptide (beta-CGRP) containing ACSF was superfused to the slice before and during hypoxia, the time at which PS began to decrease and got in complete abolishment were both postponed, and HIP were delayed or disappeared. After reoxygenation the recovery rate of PS was obviously higher in slices treated with CGRP than the control slices and the protective effect of CGRP was dose-dependent. In addition, superfusion of CGRP after hypoxia also increased the recovery of PS. These results indicate that (1) the time for the appearance of attenuation and disappearance of PS are varied according to the degree of hypoxia; (2) CGRP has a neuronal protective action against hypoxia. PMID- 7878482 TI - [The binding sites of 3H-toosendanin in rat cerebral cortex homogenate]. AB - Since early time the bark and fruit of some species of plants belonging to family melia have been used as ascaris vermifuge in traditional Chinese medicine. In our previous studies it was shown that toosendanin, a triterpenoid derivative extracted from the bark of Meli toosendan Seib et Zucc was a neuromuscular blocker acting selectively and irreversibly on the release of acetylcholine from the nerve terminals. It was thus suggested that toosendanin binding sites should exist in presynaptic nerve terminals. The binding experiments of 3H-toosendanin to the pellet of rat cerebral cortex homogenate demonstrated that the binding site of 3H-toosendanin exists in the cortex homogenate. The equilibrium dissociation constant (KD) of toosendanin-binding site complex is about 2.0 x 10( 7) mol/L. The specific binding activity of the homogenate pellet estimated according to the binding data is about 2.7 x 10(-12) mol per mg protein. The Hill coefficient of this binding site is 0.97. Our data also indicated that the synaptosomes prepared by sucrose density gradient ultracentrifugation are enriched with components of toosendanin binding site. PMID- 7878478 TI - Primary systemic amyloidosis: clinical and laboratory features in 474 cases. PMID- 7878481 TI - [Effects of interleukin-1 and interleukin-2 on electrophysiological characteristics of rat hippocampal neurons in culture]. AB - The effects of recombinant human interleukin-1 beta (rhIL-1 beta) and interleukin 2 (rhIL-2) on the cultured rat hippocampal neurons were investigated with intracellular recording and extracellular micropressure ejection techniques. Experimental results showed that all of the neurons tested with rhIL-1 beta (100 U/ml) exhibited a 4.20 +/- 1.86 mV membrane hyperpolarization. 50% of the neurons treated with rhIL-2 (100 U/ml) showed a depolarization of 11.12 +/- 3.71 mV accompanied by bursting activity, while in a still higher concentration (1,000 U/ml) a 3.25 +/- 0.63 mV hyperpolarization was observed. All the above effects of rhIL-1 beta and rhIL-2 on the hippocampal neurons were completely reversible. The membrane resistance of the neurons was not significantly affected by these cytokines. These results suggest that the effects of cytokines IL-1 and IL-2 on the excitability of hippocampal neurons may be a way by which the immune system exerts a regulatory action on hippocampal function. PMID- 7878483 TI - [Changes of auditory brainstem response and auditory cortex response after exposure to intensive noise]. AB - Auditory brainstem response and auditory cortex response were recorded repeatedly in 35 guinea pigs after exposure to intensive white noise (125 dB, 150 min.) for 62 d. the amplitude of evoked potential of acoustic nerve was decreased by 29% (P < 0.05), of the cochlear nuclei by 28% (P < 0.05). However, the amplitude of response of superior olives nuclei was increased by 21% (P < 0.05), of the inferior colliculi by 37% (P < 0.05), of the cortical evoked response by 131% (P < 0.001). The results indicate that the amplitudes of auditory evoked potential showed a centripital augmentation after exposure to intensive noise. The centripital augmentation was observed not only during the period of the temporary threshold shift (TTS) but also during that of the permanent threshold shift (PTS). PMID- 7878484 TI - [Mismatch negativity (MMN) to very short interval between regular tones]. AB - The Mismatch Negativity (MMN) component of the auditory event-related potential (AERP) is elicited by infrequent, physically "deviant" stimuli in a sequence of frequent homogeneous stimuli ("standard"), for instance, by a change in frequency, intensity or duration etc. When the inter-stimulus interval (ISI) of tone pips was occasionally shortened either to 300, 150, 75, 60 and 52 ms from regular ISI 600 ms, which resulted in the elicitation of MMN. The amplitude of MMN elicited by occasional shorter ISI was not reduced as a function of ISI shortening. This indicates that the MMN is not just due to activation of new afferent elements by deviant stimulus. Thus, by no means the elicitation of the MMN can be explained on the basis of the refractoriness. PMID- 7878485 TI - [Effects of NG-nitro-L-arginine and reduced hemoglobin on endothelium-dependent relaxation of mesenteric artery in SHRsp]. AB - It was verified in our previous study that endothelium-dependent relaxation (EDR) in the mesenteric artery strip of adult spontaneously hypertensive rats (SHR and SHRsp) was decreased upon addition of acetylcholine (ACh). In order to explore further the mechanism of this decrease of EDR, the effects of NG-nitro-L-arginine (L-NNA) (a NO synthase inhibitor) and reduced hemoglobin (RHb) (a scavenger of EDRF) on this ACh EDR were investigated in both stroke-prone SHR (SHRsp) and control WKYs. Our results showed that the difference of EDR (ACh 10(-8)-10(-5) mol/L) between SHRsp and WKY disappeared in the presence of L-NNA (10(-3) mol/L), but addition of RHb (10(-5) mol/L) would abolish such a difference only at ACh 10(-7)-10(-8) mol/L. In comparison to changes of EDR (ACh 10(-8)-10(-5) mol/L) between post L-NNA and post RHb in WKY and in SHRsp, no significant difference was found in WKY, but significant difference was found in SHRsp. And also, it appeared that the sensitivity of intact endothelium mesenteric artery of SHRsp to RHb was similar to WKY, but that to L-NNA is lower than that of WKY. Consequently it is considered that in the attenuation of EDR in hypertensive visceral vessels, the EDRF mechanism and endothelial L-arg-NO pathway are not identical. PMID- 7878486 TI - [Electrophysiological characteristics of morphologically identified chandelier interneurons in rat hippocampal slices]. AB - Using standard intracellular recording and staining techniques, 4 chandelier interneurons were sampled and anatomically confirmed from 39 physiologically identified interneurons in rat hippocampal slices. Compared to pyramidal and granule cells, all 4 chandelier interneurons-(CA1 region, n = 3, dentate gyrus, n = 1) had typical action potentials of interneurons, i. e., a shorter duration of action potential was followed by a deep after hyperpolarization. However, all these 4 cells exhibited a varying degree of spike frequency adaptation in response to depolarizing current injection, which usually do not occur in basket interneurons. Morphologically, axonal terminals of chandelier cells were beaded and exclusively distributed in the stratum oriens of the CA1 and the granule cell layer of the dentate gyrus, where the initial segments of pyramidal and granule cells are located. These results indicate that the chandelier interneurons differ from basket interneurons in the rat hippocampus with in physiology and in morphology. PMID- 7878488 TI - Tuberculosis: pathogenesis and laboratory diagnosis. AB - Emerging molecular biologic technologies hold the promise of more rapid diagnosis of tuberculosis and more definitive epidemiologic linkages of cases of TB. In addition to reviewing the pathogenesis of tuberculosis, this chapter covers a variety of methods for the rapid detection of the disease, including the acid fast smear, conventional culture, the BACTEC system, immunodiagnostic methods, and DNA-based techniques. PMID- 7878487 TI - [Rostral ventrolateral medulla-sympathetic vasoconstrictor nerve system mediated insular cortex-pressor response]. AB - In urethane-anesthetized, tubocurarine-immobilized and artificially ventilated rats, microinjection of L-glutamate (Glu) into the insular cortex (INS) caused a rise in blood pressure and heart rate. Bilateral injection of either phentolamine, propranolol or atropine into the rostral ventrolateral medulla (RVL) all could decrease the INS-pressor response. The latter could also be attenuated by phentolamine (i.v.), but not by propranolol or methyl atropine. These results indicate that the INS-pressor response is mediated by RVL (alpha-, beta- and M-receptors) -sympathetic vasoconstrictor nerve system. PMID- 7878489 TI - The relationship between TB and HIV infections. AB - AIDS is widely believed to be the strongest influence on the spread of tuberculosis, one of the most common opportunistic infections in people infected with the human immunodeficiency virus. In this chapter, the author details the unique interrelationship between these two widespread infections as well as their epidemiology, pathogenesis, clinical manifestations, prevention, and treatment. PMID- 7878490 TI - Epidemiology of tuberculosis among health care workers. AB - The author explores factors such as poor environmental, hygienic, and infection controls for the excessive conversion rates found among health care workers in numerous studies. In his in-depth discussion, Dr. Markowitz reviews the role of outbreak investigations, surveillance studies, and current epidemiologic studies in efforts to control the hazard of airborne tuberculosis in the workplace. PMID- 7878491 TI - Control of tuberculosis in the workplace: engineering controls. AB - In this review of engineering controls that can be used to check the spread of tuberculosis in health care settings, the authors address types of ventilation and supplements to ventilation such as HEPA filtration and ultraviolet germicidal irradiation. They also specifically cover engineering controls for use during medical procedures that pose an increased risk for transmission of TB. PMID- 7878492 TI - The role of respiratory protective devices in the control of tuberculosis. AB - In this comprehensive review, the authors describe various types of respirators and the major issues in their application to TB control, including the degree of protection they offer and cost. Recent recommendations regarding the use of respiratory protective devices also are discussed. PMID- 7878494 TI - Regulatory considerations of occupational tuberculosis control. AB - The authors argue that the classic hierarchy of industrial hygiene controls may be successfully used to control TB. Various elements of hygiene control programs reviewed here include TB exposure control programs, identification and isolation of patients, respiratory isolation, local source capture ventilation, laboratory procedures, employee surveillance programs, reporting of occupational illnesses, labeling requirements, and respiratory protection. PMID- 7878493 TI - Tuberculosis in the workplace: a labor perspective. AB - It was not until several health care unions petitioned OSHA for a bloodborne pathogen standard in 1986 that OSHA began to play a major role in regulating the health care industry. The authors examine the Service Employees International Union's current effort to urge OSHA to develop a standard to protect workers from occupational exposure to TB. They also cover ramifications of the CDC's revised guidelines for preventing the transmission of TB in health care settings. PMID- 7878495 TI - Educating workers about tuberculosis. AB - At a state penitentiary, workers are told that the communicable disease unit is a safe environment in which to work due to the negative air pressure in the isolation rooms and the improved ventilation system. However, nobody is trained to monitor the system or understands the role of negative air pressure, and isolation room doors are occasionally left open. As a result, workers are reluctant to work in the unit. At a soup kitchen, workers refuse to serve people with HIV due to fear of tuberculosis transmission. They have heard that people infected with HIV are likely to have TB and, therefore, to protect themselves, they feel the soup kitchen should not serve people with HIV. In a large, urban social service agency, workers buy masks and begin wearing them to work when they hear a coworker has tuberculosis. Pictures of them in the newspaper instigate a string of similar actions in other agencies. Emergency room workers in a city hospital have been told they are not at increased risk of contracting TB, because they do not have prolonged contact with infectious patients. However, when they discover that several coworkers tested positive on PPD screening tests, they go to their union demanding action. PMID- 7878496 TI - Medical surveillance for workers exposed to tuberculosis. AB - This detailed discussion of medical surveillance techniques addresses such issues as the administration and interpretation of the tuberculin skin test, the importance of BCG vaccine, preventive therapy with isoniazid, the identification of groups at high risk for TB, multidrug-resistant tuberculosis, and regulatory requirements for PPD testing, including CDC guidelines. PMID- 7878497 TI - Control of tuberculosis in the workplace: toward an integration of occupational health and public health. AB - The authors discuss current efforts at and obstacles to forging a link between public health and occupational health in the control of tuberculosis. They trace the historical roots of TB in the workplace as well as the current crisis that has resulted from the emergence of both the AIDS and tuberculosis epidemics. The authors also detail how the CDC's guidelines embody a comprehensive approach to TB control. PMID- 7878498 TI - Future needs: research, education, and service. AB - Sections on research, education, and service summarize efforts that are needed to control the workplace transmission of TB and measures that can be taken while research is being carried out. Topics include ways to identify infectious patients, techniques for measuring the airborne concentration of TB, and the need for surveillance programs. PMID- 7878500 TI - The Gerald Marks Lecture. New technology. Temptations, challenges, and educational implications. PMID- 7878499 TI - Tuberculosis in office settings: the anxiety and the reality. AB - Using three case studies as examples, the director of a major insurance carrier's employee health service shares his perspective on the importance of the early identification of potential exposures, screening for tuberculosis, and communicating to employees. He emphasizes that "an appropriate level of vigilance" can prevent or minimize a significant number of workplace exposures. PMID- 7878501 TI - Response of serum cytokines in patients undergoing laparoscopic cholecystectomy. AB - The clinical observation that a laparoscopic cholecystectomy is a minimally invasive operation has not been demonstrated on a biochemical basis. Interleukin 6, a known endogenous pyrogen and hepatocyte-stimulating protein, correlates with the significance of surgical trauma. Utilizing the IL-6 immunoassay, we studied this biochemical parameter of trauma to compare its response in laparoscopic vs open cholecystectomy. Sixteen patients who underwent only laparoscopic cholecystectomy showed peak IL-6 concentrations of 51 pg/ml (22-86) vs a peak IL 6 concentration of 124 pg/ml (56-225) for open cholecystectomy. Six additional patients who underwent an ERCP followed by laparoscopic cholecystectomy showed a dramatic rise in peak IL-6 concentration to 315 pg/ml (15-634). These results biochemically confirm the true minimal invasiveness of laparoscopic cholecystectomy. The findings in the ERCP-followed-by-laparoscopic cholecystectomy group support the theory that two invasive procedures in close proximity may prime the cytokine system in its response to surgical trauma. PMID- 7878502 TI - Preservation of immune response after laparoscopy. AB - We evaluated the immunologic responses following laparoscopic and open surgery by comparing delayed type hypersensitivity induration size before and after each method of accessing the abdominal cavity. One hundred and thirty-two male Sprague Dawley rats were sensitized with keyhole limpet hemocyanine (KLH). Animals were challenged with KLH and phytohemaglutanin (PHA) 10 days after sensitization. On day 14 after initial sensitization animals were randomly divided into three groups. Group one served as controls and had no procedure performed, group two underwent peritoneal insufflation with carbon dioxide gas to a pressure of 6-8 mm Hg for one half hour, and rats in group three had a midline laparotomy which was closed after one half hour. Each rat was challenged with KLH immediately and at three days postoperatively. The area of induration in response to each of the challenges was measured with calipers 24 and 48 hours after the challenge. Results of this skin testing showed that the group of animals that underwent laparotomy, despite having normal responses preoperatively, had significantly diminished responses to both KLH and PHA when challenged postoperatively. The insufflated group showed no differences from control animals at any time point examined. We conclude that DTH response in this model is better preserved after laparoscopy than laparotomy. We further conclude that the defect in DTH response is in the effector arm. The question of the clinical significance of these findings is addressed. PMID- 7878504 TI - Laparoscopic Billroth II gastrectomy in the canine model. AB - The feasibility and safety of laparoscopic Billroth II gastrectomy were evaluated in an animate model. After developing the technique in acute animal experiments, laparoscopic antrectomy and Billroth II anastomosis was performed in six mongrel dogs. Video laparoscopic access to the peritoneal cavity was accomplished with six ports (five, 10 mm; one, 12-18 mm). The operations were performed without complication in 150-200 min (mean +/- SEM, 171 +/- 10 min). The animals tolerated solid oral meals on the 2nd or 3rd postoperative day. One dog developed frequent diarrheal stools and lost 3.4 kg prior to sacrifice 18 days postoperatively when a gastroileostomy was discovered. The remaining five animals did well and were sacrificed at 49-77 days postoperatively. Adhesions were minimal and the gastrojejunostomy was widely patent in all animals without evidence of leakage or obstruction. Laparoscopic Billroth II gastrectomy in the canine model is thus feasible and safe. Using laparoscopic guidance, it may be more difficult to identify the ligament of Treitz, which must be assured at the time of operation. PMID- 7878507 TI - Development of a new insertion technique and a new device for the placement of bifurcated airway stents. AB - We developed a new insertion technique and designed a forceps device for the placement of bifurcated airway stents; 131 of 142 endoscopically placed tracheobronchial Y-stents were inserted with a forceps and a laryngoscope. For the last 52 stent implantations we used the new stent forceps. It was determined to be a simple and safe method without major complications. In 11 cases alternative techniques had to be used. Technique and device are described in detail. PMID- 7878503 TI - Laparoscopic trans-cystic-duct common-bile-duct exploration. AB - One thousand seventy-one consecutive laparoscopic cholecystectomies were performed. Routine cholangiography was employed with a 99% success rate. One hundred thirty patients were found to have common duct stones (CBDS). In 48 (37%) patients they were unsuspected. One hundred eleven patients underwent attempted trans-cystic-duct extraction techniques (TCD-CBDE). One hundred three (93%) were successful. The following techniques were employed: 101--biliary endoscopy, 23- ampullary balloon dilation, 2--fluoroscopic basket retrieval. The average operative time was 136 min. The average postsurgical stay was 3.7 days. There were 19 (17%) complications--6 (5%) major. There were 4 retained stones (2 intentional) and 1 death. Patients over 65 years of age had more complications and patients with unsuspected CBDS under 65 years of age had the fewest. TCD-CBDE is a safe, effective way to extract common duct calculi. Endoscopy and basket stone retrieval was the primary technique employed. PMID- 7878505 TI - Laparoscopic management of choledocholithiasis. AB - The authors report on a group of 114 patients with common bile duct (CBD) stones who were treated by laparoscopic surgery. Management through the cystic duct was considered the first option. Choledochotomy was used for those patients in which the cystic approach was not possible or was unsuccessful. Transcystic lithotripsy was considered for patients with CBD stones in disproportion with the size of the cystic duct. Laparoscopic antegrade sphincterotomy was indicated as a drainage procedure. The transcystic approach was used in 89.5% of the patients; choledochotomy was used in 6.2%; and both ways were used in 4.3%. Different procedures were used, including mechanical and electrohydraulic lithotripsy, choledochotomy with T-tube or endoprostheses drainage, laparoscopic sphincterotomy, end-to-end common bile duct anastomosis, and choledochoduodenum anastomosis. One of the patients was in the 21st week of pregnancy. The laparoscopic approach to choledocholithiasis was successfully performed in 94.8% of the patients. Mean hospital stay was 1.7 days. There was a 6.2% incidence of complications and the mortality rate was 0.9%. In 84.3% of the patients, the transcystic approach was used successfully, with a complication rate of 4.9% and a mean hospital stay of 1.6 days. Three patients were converted to open surgery early in this series. Thus far, one patients has presented residual CBD stones. The results obtained suggest that laparoscopic common bile duct exploration is a technically feasible procedure, with low complication and mortality rates, although it requires adequate selection of patients and a variety of techniques and types of equipment. PMID- 7878508 TI - DNA analysis with flow cytometry and image cytometry in colorectal polyps. AB - Ploidy was studied with flow and image cytometry in 51 polyps removed endoscopically from 44 patients. Evaluation was carried out on frozen material in 34 cases and on material fixed in formalin and embedded in paraffin in the remaining 17. Data analysis showed a statistically significant correlation between polyp size and aneuploidy frequency (P > 0.05). No statistically significant correlation was found between aneuploidy frequency and histological type. The linear correlation study did, however, show a correlation tendency between histological type and aneuploidy (R = 0.42211). PMID- 7878506 TI - A comparison of laparoscopic and open hernia repair as a day surgical procedure. AB - To evaluate the merits of laparoscopic inguinal hernia repair (LHR) compared to conventional open hernia repair (OHR) a randomized study has been conducted. All patients were day surgical cases, of which 44 were randomized to a standardized OHR under local anesthetic (LA) and 42 to an LHR under general anesthesia (GA). Fifteen LHR patients had bilateral repairs. Operative time for OHR was 30.5 min, for unilateral LHR 35 min, and for bilateral LHR 60 min. OHR patients were discharged after a median of 134.5 min, which was significantly shorter than LHR patients, whose median discharge was 225 min (P < 0.01). Pain scores, activity levels, analgesia requirements, and time taken to return to work were not significantly different following surgery in either group (P < 0.05). There have been two recurrent hernias and one small bowel obstruction in the LHR group. We conclude that both repairs can be successfully performed as day surgical procedures. The added cost of LHR at this stage does not warrant its widespread use in unilateral hernia repairs. Which procedure is adopted should be individualized; however, patients with bilateral hernias on presentation can be successfully managed as day cases, obviating the need for hospitalization or two operations. PMID- 7878510 TI - A pig model for advanced laparoscopic biliary procedures. AB - Advanced laparoscopic biliary procedures can be undertaken in a pig model, but the small size of the normal common bile duct makes learning difficult. We have developed a prepared pig model of common bile duct ligation on which to practice advanced laparoscopic biliary surgery. The pig's distal common bile duct was occluded using several different methods via a minilaparotomy. Laparoscopic biliary procedures were undertaken 6-21 days later. The common bile duct became dilated to between 2 and 3 cm in diameter in all cases, and this was well tolerated by the animals. All advanced laparoscopic biliary procedures were possible, including choledochoscopy, exploration of the bile duct, and cholecystojejunostomy. Short-term common bile duct ligation is well tolerated in pigs and can be used to create a model for practicing advanced laparoscopic biliary procedures. PMID- 7878509 TI - Laparoscopic Rosetti fundoplication. AB - Early experiences with laparoscopic fundoplication using the Rosetti technique are presented and compared with retrospective results from conventional fundoplication procedures. A 360 degrees floppy fundoplication was laparoscopically constructed without division of short gastric vessels. We have performed 60 consecutive procedures. Conversion to open surgery was done in seven cases due to anatomical reasons and in two due to progressive subcutaneous emphysema and CO2-retention. The complication rate was low. The range of postoperative hospital stay is 1-4 days for non-converted patients. Symptomatic follow up has hitherto been performed in 41 patients with a follow-up time of 3-9 months. Regurgitation and heartburn had disappeared in all but one patient. The follow-up results do not differ from those achieved in patients operated upon with the conventional open Nissen (N = 41), Toupet (N = 9) or Rosetti (N = 36) technique. Pre and postoperative control of 24h pH and lower esophageal sphincter pressure (LESP) in 19 laparoscopically treated patients showed normalisation of LESP in all cases and postoperative 24h pH < 4 ranging between 0 and 3%. Assessment of quality of life showed postoperative results in accordance with normal population for all treated groups. PMID- 7878511 TI - Laparoscopic resection of a retroperitoneal cystic lymphangioma. AB - The success of laparoscopic cholecystectomy has expanded the scope of laparoscopic procedures and resection of retroperitoneal organs and selected cystic intraadominal masses have been performed by minimally invasive surgical techniques. We report the case of a 45-year-old that presented a retroperitoneal cystic lymphangioma that was successfully excised by a laparoscopic approach. Laparoscopic surgical techniques should be considered for treatment of selected cystic lesions of intrabdominal or retroperitioneal origin. PMID- 7878512 TI - Laparoscopic treatment of lymphoceles following kidney transplantation by intraperitoneal fenestration and omentoplasty. AB - The recent development of endoscopic surgery and its use in treating several abdominal and thoracic surgical pathologies lead us to suggest its application in the treatment of posttransplant lymphoceles. The authors report two cases treated by the laparoscopic approach. Recurrence occurred in one of them. The technique is described and its place among other therapeutic modalities is discussed. PMID- 7878513 TI - Endoscopic laser pancreatic cystogastrostomy. An alternative for internal drainage of pancreatic pseudocysts. AB - Traditionally the drainage of pancreatic pseudocysts has been carried out operatively, forming a cystenterostomy. A simple endoscopic method of forming a pancreatic cystogastrostomy with laser is presented. This procedure does not require a general anesthetic, is safe, and allows resolution of symptoms. PMID- 7878514 TI - Hepatic metastasis after laparoscopic cholecystectomy for polypoid gallbladder cancer followed by radical surgery. AB - While laparoscopic cholecystectomy is being increasingly performed on patients with gallbladder disease, this approach in cases of polypoid lesions in the gallbladder may not always be justified. We report here a case of early development of intrahepatic metastasis after laparoscopic cholecystectomy for polypoid gallbladder cancer; wedge resection of the gallbladder bed and dissection of regional lymph nodes had to be done. When a malignancy of the gallbladder is suspected during preoperative examinations, open cholecystectomy should be done. PMID- 7878515 TI - Laparoscopic repair of a Morgagni hernia. AB - Laparoscopic repair of a diaphragmatic hernia through the right sternocostal foramen of Morgagni in an obese 42-year-old man is described. The indications for surgery were symptoms of strain-induced dyspnea and tightness in the chest. The technique was carried out by incorporating a marlex mesh into the defect and fixing it in place with hernia staples. The patient had an immediate recovery after repair of the hernia and has remained free of recurrence or complaints 9 months after surgery. PMID- 7878516 TI - Technique and results of routine dynamic cholangiography during 528 consecutive laparoscopic cholecystectomies. AB - With the advent of laparoscopic cholecystectomy a trend toward more extensive preoperative diagnostic study of the biliary tree by intravenous cholangiography or ERCP has been observed. However, both exams have technical limitations and are not without risk. We report our experience with 500 consecutive routine dynamic intraoperative cholangiographies during laparoscopic cholecystectomy, 97% of which were successful. No lesions from cholangiography were observed. In ten patients clips on the cystic artery appeared on intraoperative cholangiogram to be too close to the hepatic duct and were removed. Anomalies of surgical importance were discovered in 11 patients (2.3%). Unsuspected stones were found in 18 cases (3.7%) and suspected stones confirmed in 12 (2.4%). In our experience routine dynamic intraoperative cholangiography provided important information in 51 cases out of 500 (10.2%). We conclude that routine dynamic intraoperative cholangiography is extremely useful for safer laparoscopic cholecystectomy and cost containment. PMID- 7878517 TI - A new 3-D laparoscope in gastrointestinal surgery. AB - This study was set up to compare three-dimensional imaging of a new three dimensional laparoscope with two-dimensional imaging in the inanimate and clinical settings. In the clinical setting the laparoscope was used in a total of 50 different laparoscopic operations. It provided excellent depth perception, definition, and resolution. The relationships of structures were more easily defined, and instrument manipulation was easier, doing away with the need for "touch and feel" to determine instrument position. Three-D imaging made cannulation of the cystic duct for cholangiography or with a flexible choledochoscope easier. In the inanimate setting basic simple tasks took the same time in 2-D as in 3-D, whereas a more complicated procedure of passing a needle and suture through a series of hoops was 25% faster when performed in 3-D compared to 2-D. Three-D imaging may reduce operative time for laparoscopic procedures, particularly the more complicated operations. PMID- 7878519 TI - Guidelines for the clinical application of laparoscopic biliary tract surgery. SAGES. Society of American Gastrointestinal Endoscopic Surgeons. PMID- 7878518 TI - Laparoscopic management of common bile duct stones. PMID- 7878521 TI - Photoreceptor outer segments in aqueous humor: key to understanding a new syndrome. AB - Retinal detachment with oral dialyses and tears of the nonpigmented epithelium of the ciliary body sometimes accompanies aqueous cells and high intraocular pressure with its marked fluctuation. The aqueous cells consist predominantly of photoreceptor outer segments which obstruct aqueous outflow at the trabecular meshwork and induce high intraocular pressure as ghost cells do in ghost cell glaucoma. A new clinical entity with the combination of these signs, namely, rhegmatogenous retinal detachment with "photoreceptor outer segment glaucoma" is designated as Schwartz-Matsuo syndrome in this report. The detection of photoreceptor outer segments in the anterior chamber indicates that a communication between subretinal space and aqueous humor has been established by some mechanism. The new syndrome should be included in differential diagnoses of iritis and glaucoma. PMID- 7878520 TI - Ocular myasthenia: a protean disorder. AB - Ocular myasthenia is a localized form of myasthenia clinically involving only the extraocular, levator palpebrae superioris, and/or orbicularis oculi muscles. Ocular manifestations can masquerade as a variety of ocular motility disorders, including cranial nerve and gaze palsies. A history of variable and fatiguable muscle weakness suggests this diagnosis, which may be confirmed by the edrophonium (Tensilon) test and acetylcholine receptor antibody titer. Anticholinesterases, corticosteroids and other immunosuppressive agents, and other therapeutic modalities, including thymectomy and plasmapheresis, are used in treatment. As the pathophysiology of myasthenia has been elucidated in recent years, newer treatment strategies have evolved, resulting in a much more favorable prognosis than several decades ago. This review provides historical background, pathophysiology, immuno-genetics, diagnostic testing, and treatment options for ocular myasthenia, as well as a discussion of drug-induced myasthenic syndromes. PMID- 7878522 TI - Elevated intraocular pressure secondary to rhegmatogenous retinal detachment. AB - Elevated intraocular pressure secondary to rhegmatogenous retinal detachment was described by Ariah Schwartz in 1972, an entity commonly known as Schwartz's syndrome. Photoreceptor outer segments identified in the aqueous of patients with this syndrome are thought to play a role in the elevation of the intraocular pressure. We present two patients with open angles and elevated intraocular pressure associated with retinal detachment. Retinal reattachment surgery resulted in normalization of the intraocular pressure. Electron microscopic examination of aqueous specimens from our patients demonstrated a predominance of photoreceptor outer segments in varying stages of degeneration. In these specimens, inflammatory cells, fibrin, and pigment granules were rarely observed or were absent. We review the literature regarding the epidemiology, clinical characteristics, and pathogenesis of Schwartz's syndrome. PMID- 7878523 TI - The eye and the eosinophil. AB - Recent work has highlighted the eosinophil's role as an effector cell in a wide array of disease entities, including parasitic infections and allergic and nonallergic diseases. The eosinophil is filled with granules containing toxic cationic proteins, capable of harming tissue when released to the extracellular space. In the eye, toxic eosinophil cationic granule proteins have been encountered in conjunctiva, cornea, tears, and contact lenses of patients suffering from ocular allergy, suggesting an effector role for the eosinophil in the ophthalmic manifestations of atopy. Laboratory investigations indicate that eosinophil granule major basic protein, the principal eosinophil granule protein, may adversely influence corneal epithelium, and promote corneal ulceration in the severest forms of ocular allergy. Further, the eosinophil may play a contributory pathophysiologic role in some nonallergic ophthalmic diseases such as Wegener's granulomatosis, orbital pseudo-tumor, and histiocytosis X. The eosinophil's morphologic, immunologic, and biochemical characteristics will be reviewed and its role in certain ophthalmic diseases thoroughly examined. PMID- 7878525 TI - Visual disturbance of the uncovered eye in patients wearing an eye patch. PMID- 7878526 TI - The Tubingen Study on Optic Neuritis Treatment--a prospective, randomized and controlled trial. PMID- 7878527 TI - Relationship between low estrogen receptor values and other prognostic factors in primary breast tumors. AB - BACKGROUND: The current study compared the immunocytochemical expression of estrogen (ER) and progesterone (PgR) receptors by malignant breast cells to the hormone receptor concentrations reported from radioligand assays. These values were examined in relation to DNA ploidy and the fraction of cells in S phase. METHODS: ER and PgR concentrations, DNA ploidy, and S-phase fractions were measured by standard techniques with 124 samples of invasive ductal carcinoma. Suspensions of tumor cells were examined by immunocytochemical assay (ICA) for the percentages of ER and PgR positive cells. RESULTS: Twenty-six of the 38 tumors from patients 50 years of age or younger were classified as high S-phase fraction, and 28 tumors had aneuploid levels of DNA. The 20 ER positive tumors each contained less than 100 fmol/mg. Thirty-nine of the 86 tumors from patients older than 50 years were classified as high S phase, and 41 were aneuploid. Sixty five samples were considered ER positive by radioligand assay. ICA showed that tumors in either age group with less than 40 fmol/mg did not contain ER positive cells. The proportion of samples with PgR levels between 10 and 100 fmol/mg was small, and fewer PgR positive tumors were categorized as negative when examined by ICA for receptor containing cells. The reclassification of the hormone receptor status of a tumor based on ICA appeared to be independent of S-phase and ploidy values. CONCLUSIONS: Tumors that are classified as ER or PgR positive based on accepted cutoff values for radioligand assays may actually be receptor negative because the tumors do not appear to contain receptor positive cells. PMID- 7878528 TI - Results of pancreaticoduodenectomy for ampullary carcinoma and analysis of prognostic factors for survival. AB - BACKGROUND: Results of pancreaticoduodenectomy for ampullary carcinoma were evaluated, and prognostic factors for survival were analyzed. METHODS: During the period from 1984 to 1992 67 patients underwent subtotal or total pancreaticoduodenectomy for ampullary carcinoma. All clinicopathologic data and their influence on survival were studied. RESULTS: Subtotal pancreaticoduodenectomy was performed in 62 of 67 patients with a mortality of 6% and a morbidity of 65%; the remaining five patients underwent total pancreaticoduodenectomy. Intraabdominal infection was the most important complication. Resection margins were tumor free in 75% of 67 patients. The overall 5-year survival was 50%. Survival was significantly influenced by the involvement of resection margins. After resection with involved margins 5-year survival was 15% and 60% after resection with free margins (p < 0.001). Tumor size, lymph node involvement, and differentiation grade had limited and not significant influence on survival. CONCLUSIONS: Subtotal pancreaticoduodenectomy is the type of resection of first choice for ampullary carcinoma. Involvement of resection margins was the strongest prognostic factor for survival. Patients with a tumor size larger than 2 cm, with lymph node involvement, or with a poorly differentiated tumor still had a 5-year survival rate greater than 40%. Patients with involved margins might be candidates for studies on adjuvant therapy. PMID- 7878529 TI - Pancreas-sparing duodenectomy: indications, surgical technique, and results. AB - BACKGROUND: Pancreatoduodenectomy, originally performed for malignancy of the pancreas and duodenum, is also commonly used for potentially malignant lesions. Because a normal pancreas should be spared, we investigated the concept of duodenectomy alone with the pancreas intact for diseases such as familial adenomatous polyposis syndrome. METHODS: Five patients underwent pancreas-sparing duodenectomy for nonmalignant lesions performed by means of meticulous detachment of the duodenum from the pancreas, transecting the bile and pancreatic ducts outside the duodenum. Reconstruction was accomplished by advancing the jejunum to anastomose end-to-end with the juxtapyloric duodenal cuff, implanting the bile and pancreatic ducts in a location corresponding to the native papilla. The hospital course, complications, and long-term follow-up status of all patients are reviewed in detail. RESULTS: No deaths occurred in this series. Delayed gastric emptying was seen in one patient and transient pancreatic fistula in another. Long-term endoscopic follow-up showed no stenosis of the ductal anastomoses. Endoscopic surveillance, including endoscopic retrograde cholangiopancreatography, was not hampered by this technique of reconstruction. CONCLUSIONS: Pancreas-sparing duodenectomy is a practical operation for nonmalignant duodenal lesions where the pancreas is not involved by the disease process. PMID- 7878530 TI - Effect of growth hormone and protein intake on tumor growth and host cachexia. AB - BACKGROUND: Growth hormone supplementation has been shown to stimulate muscle protein synthesis and to improve nitrogen balance in a variety of catabolic states. The role of growth hormone to support the tumor-bearing host is complicated by the risk that growth hormone or its intermediaries may stimulate tumor growth. The purpose of this study is to examine the effect of growth hormone supplementation in tumor-bearing rats. This is studied in the protein-fed and protein-starved state in an attempt to isolate a selective benefit for the host over the tumor. METHODS: Forty Lewis rats bearing a metastatic mammary adenocarcinoma (MAC-33) were divided into four groups: one receiving a regular diet plus saline solution, one receiving a regular diet plus growth hormone (1 IU/kg/day), one receiving protein-depleted diet plus saline solution, and one receiving a protein-depleted diet plus growth hormone. After 25 days of growth hormone treatment, animals were killed to determine primary tumor size, tumor/carcass ratio, host organ composition, pulmonary metastasis, and serum amino acid levels. RESULTS: The tumor/carcass ratio was decreased as a result of growth hormone treatment in both the protein-fed and protein-starved groups. Growth hormone supplementation resulted in increased carcass weight, muscle weight, and muscle protein content in the protein-fed, tumor-bearing animals (p < 0.05). In the protein-starved, tumor-bearing rats growth hormone supplementation resulted in a significant decrease in tumor volume and tumor protein content. Amino acid analysis suggests that the amino acid tyrosine is a rate-limiting substrate for tumor cell proliferation in this model. CONCLUSIONS: Growth hormone has a differential effect on tumor and host growth in the protein-fed and protein starved state. Growth hormone supplementation inhibited tumor growth in protein deprived animals. This is most likely accomplished indirectly by limiting amino acid substrate availability to the tumor. PMID- 7878531 TI - Surgery for patients with thyroid carcinoma invading the trachea: circumferential sleeve resection followed by end-to-end anastomosis. AB - BACKGROUND: Curative surgery can be accomplished by tracheal resection in patients with thyroid carcinoma invading the trachea; however, there is controversy regarding the extent of the tracheal resection. In this study we investigated by means of histologic examination the mode of tracheal invasion by thyroid carcinoma. METHODS: Twenty-one patients with thyroid carcinoma invading the trachea underwent circumferential sleeve resection of the involved trachea. The extent of invasion of the tracheal wall on the adventitial and mucosal sides was compared on histologic examination. RESULTS: Three to nine tracheal rings were resected. Assessment of longitudinal spread showed that one to six rings (mean; 3.1 rings) were invaded on the adventitial side but only zero to four rings (mean; 1.9 rings) on the mucosal side, with invasion on the mucosal side never exceeding invasion on the adventitial side. In contrast, examination of circumferential spread showed invasion on the mucosal side exceeding invasion on the adventitial side in five cases. CONCLUSIONS: Our results suggest that when the extent of invasion of the adventitia is considered, carcinoma tissue may be left behind on the mucosal side of the trachea when partial wedge resection is performed and that, whenever feasible, circumferential sleeve resection should be performed in patients with thyroid carcinoma invading the trachea. PMID- 7878524 TI - Central American mesencephalopathy. AB - A 31-year-old Hispanic laborer sought medical attention for a four-day history of posterior headaches and double vision. The headache spontaneously resolved, but the patient continued to experience vertical diplopia. The neuro-ophthalmic exam revealed minimal anisocoria and subtle deficits of vertical motion of the left eye. MRI scanning demonstrated a lesion within the midbrain on the left side. Lumbar puncture revealed cells consisting primarily of lymphocytes and eosinophils. Both serum and cerebrospinal fluid revealed glycoproteins indicative of a cysticercosis infection. The patient was treated with Praziquantel and steroids with improvement of his oculomotor function. PMID- 7878533 TI - Platelet attachment stimulates endothelial cell regeneration after arterial injury. AB - BACKGROUND: Arterial injury is associated with endothelial disruption and attachment of platelets to an exposed subintimal layer. A variety of factors released by platelets may affect the ability of endothelial cells bordering an injury to regenerate. In this study an organ culture model of arterial injury was used to investigate the relationship between attachment of platelets to a superficial arterial injury and endothelial regeneration. METHODS: A defined superficial endothelial injury was made in whole vessel wall explants of rabbit thoracic aorta. Injured explants were treated with either fresh whole platelets, the supernatant of platelets aggregated by collagen, or basic fibroblast growth factor. Four days after injury and treatment, the average distance of endothelial regeneration was determined. RESULTS: A dramatic increase in the rate of endothelial cell regeneration was observed when injured vessels were exposed to fresh whole platelets (p = 0.003). This increase in regeneration was comparable to that observed with fibroblast growth factor. No increase in the regenerative rate was found after exposure of explants to the supernatant of aggregated platelets (p = 0.69). CONCLUSIONS: Platelets stimulate endothelial regeneration at a rate equal to that observed with the potent endothelial mitogen basic fibroblast growth factor. Because this effect was not demonstrated with the supernatant of aggregated platelets, endothelial regeneration may be dependent on attachment of the platelets to the area of injury. PMID- 7878535 TI - Laparoscopic drainage of lymphoceles after kidney transplantation: indications and limitations. AB - BACKGROUND: Symptomatic lymphoceles are not uncommon after kidney transplantations. Surgical marsupialization with internal drainage is the treatment of choice. However, laparoscopic drainage is reportedly as effective, with only minimal trauma. METHODS: We attempted 14 laparoscopic lymphocele drainages during a 3-year period and studied the indications and limitations, using intraoperative ultrasonography in all cases. RESULTS: Laparoscopic drainage was successful in only 9 (64%) of 14 patients. A conversion to open laparotomy was necessary in five patients; their lymphoceles were lateral and either posterior or inferior to the kidney. Two patients with initially successful laparoscopic drainage required conversion to open laparotomy 21 and 83 days later; their lymphoceles were inferior to the kidney. Laparoscopic drainage shortened the median hospital stay by 4 days versus open surgical drainage and by 7 days versus conversion. Hospital costs for laparoscopic drainage averaged $7400 less versus open drainage and $10,300 less versus conversion. CONCLUSIONS: In patients with symptomatic lymphoceles medial and either superior or anterior to the kidney, laparoscopic drainage under intraoperative ultrasonographic guidance is easy, safe, and effective. It decreases hospitalization, convalescence, and costs. In patients with symptomatic lymphoceles lateral and either posterior or inferior to the kidney, laparoscopic drainage may fail because of anatomic inaccessibility and technical impracticability. PMID- 7878534 TI - Guided percutaneous drainage for posttraumatic empyema thoracis. AB - BACKGROUND: Guided percutaneous drainage (GPD) is used in the management of posttraumatic empyema thoracis; however, its equivalence to decortication has not been evaluated. METHODS: We retrospectively reviewed the records of 12 patients who underwent GPD and nine who were treated with decortication. RESULTS: No primarily GPD-managed empyemas necessitated a subsequent thoracotomy. The size and number of fibrinopurulent loculations treated by each technique were equivalent. Sterile purulent collections were found in 55.6% of decortication treated patients and in 33% of patients who underwent GPD. Intrapleural analgesia was administered to 71.4% of decortication-treated patients and 28.6% of GPD treated patients. Five patients undergoing decortication required intensive care unit monitoring after operation (average, 2.8 days), compared with no GPD-treated patients. The catheter was left in place at discharge in 41.6% of GPD-treated patients and was removed on an outpatient basis. CONCLUSIONS: The efficacy of GPD in handling loculated pleural space infections equals that of decortication. An intensive care unit stay is avoided. The ability to discharge patients with external drainage catheters and the decreased requirement of pain control should reduce the number of inpatient hospital days. GPD is an effective first-line approach for posttraumatic empyema thoracis. PMID- 7878541 TI - Shear stress-conditioned, endothelial cell-seeded vascular grafts: improved cell adherence in response to in vitro shear stress. AB - BACKGROUND: Prosthetic vascular grafts with adherent endothelial cell monolayers may prove useful for small-caliber vessel bypass. However, endothelial cells adhere poorly to prosthetic graft material, and they are stripped when exposed to in vivo shear stress. This study sought to determine whether in vitro shear stress conditioning improves endothelial cell adhesion and decreases thrombogenicity of endothelial cell-seeded grafts. METHODS: The lumens of 1.5 mm (inside diameter) spun polyurethane polymer vascular grafts were seeded with bovine aortic endothelial cells and cultured in vitro for 6 days with or without continuous laminar shear stress, first at 1 to 2 dynes/cm2 for 3 days, then at approximately 25 dynes/cm2 for 3 days. Grafts preconditioned by shear stress and the static control grafts were then exposed to arterial shear stress at 25 dynes/cm2 for 25 seconds. The number of dislodged cells was counted, and the grafts were examined by light and scanning electron microscopy. Whole blood clotting time in the grafts was also determined. RESULTS: Exposure of grafts to acute shear stress dislodged 1.35 x 10(6) +/- 0.44 x 10(6) cells from static grafts compared with 1.05 x 10(4) +/- 0.16 x 10(4) cells from grafts preconditioned by shear stress. By light and electron microscopy an intact endothelial monolayer was observed to cover the lumen of shear stress-conditioned grafts, whereas few cells remained on the luminal surface of grafts not previously exposed to shear stress. The clotting time in shear stress-conditioned grafts was significantly prolonged in relation to grafts not exposed to shear stress. CONCLUSIONS: These findings show that endothelial cell adhesion and retention on vascular grafts in vitro is markedly enhanced by preconditioning the seeded endothelial cell monolayer with long-term shear stress. Consequently, vascular grafts containing shear stress-conditioned endothelial monolayers are less thrombogenic in vitro than small-caliber vascular grafts without intact endothelial cell monolayers. PMID- 7878536 TI - Repeat liver resections from colorectal metastasis. Repeat Hepatic Metastases Registry. AB - BACKGROUND: A retrospective multiinstitutional study was performed to assess survival benefits of patients undergoing repeat liver resection for colorectal metastasis. An updated report is presented here. METHODS: The series comprised 170 patients from 20 different institutions around the world. Mean age of patients was 58 years (range, 28 to 84 years). The mean and median follow-up were 29 and 25 months, respectively. RESULTS: Three- and 5-year overall survival rates were 45% and 32%, respectively. The Dukes' stage of the primary tumor showed a 34% 5-year survival rate for those patients with negative nodes and 30% if nodes were positive (p = 0.42). The disease-free interval between liver resections showed a better outcome for those who had undergone repeated liver resections less than 1 year from the first liver resection (42% versus 23% 5-year survival rates); the difference was not significant (p = 0.58). The number of metastases found and resected at second procedures did not show significant differences in survival and was probably due to selection criteria. Anatomic resections reached a better 5-year survival rate (39%) than wedge resections (21%). The difference was not statistically significant (p = 0.2). The presence of extrahepatic disease and residual liver tumor left behind when repeat liver resection was performed were the most important prognostic variables in survival. Patients with extrahepatic disease had 19% 5-year survival rate, whereas those without disease outside the liver had 36% 5-year survival rate (p = 0.09). Patients with complete resections and those with residual liver disease after repeat resections had 36% and 17% 5-year survival rates, respectively (p = 0.01). Presence of postoperative morbidity after second liver resections did not show a significant negative impact in survival (p = 0.70). Adjuvant therapies were not widely used after liver resections and did not seem to improve prognosis of patients who were treated (39% versus 29% 5-year survival rates, p = 0.9). CONCLUSIONS: Repeat liver resections for colorectal metastasis is a justified approach because surgery remains the only potentially curative treatment. These procedures are relatively safe with low morbidity and mortality rates. Long-term survival (32%) can only be achieved in selected patients. PMID- 7878542 TI - Latex allergy--report of an anaphylactic reaction. PMID- 7878532 TI - Surgery for adult polycystic liver disease. AB - BACKGROUND: Occasionally patients with adult polycystic liver disease (APLD) have symptoms. For these patients surgery may represent a valuable therapeutic option to relieve symptoms. METHODS: From September 1977 to August 1993 at our institution, 10 women with APLD were examined and surgically treated. They underwent a partial hepatic resection together with cyst fenestration. The surgical outcome and long-term follow-up were retrospectively analyzed. RESULTS: Postoperative morbidity consisted of one case of pneumonia, and one case of acute pancreatitis with deep vein leg thrombosis. One patient died after acute Budd Chiari syndrome developed as a result of liver collapse after fenestration of a posterior cyst. In the long term six of nine patients were symptom free. Late surgical complications included acute cholecystitis (one patient), small bowel obstruction (one), and incisional hernia (two). CONCLUSIONS: A combined surgical approach of hepatic resection and cyst fenestration has proved feasible for patients with highly symptomatic APLD. Extensive fenestration of posterior cysts should be avoided; transverse hepatic resection (frontal hepatectomy) up to the costal margin is proposed. This therapy provides good results at long-term follow up. PMID- 7878543 TI - Pregnancy after total pancreatectomy and autologous islet transplantation. PMID- 7878538 TI - Selective inhibition of cyclic adenosine monophosphate-mediated pulmonary vasodilation by acute hypoxia. AB - BACKGROUND: Adult respiratory distress syndrome is characterized by hypoxia and acute pulmonary hypertension. Therefore we examined the effect of acute hypoxia on the mechanisms of pulmonary vasodilation. METHODS: Isolated rat pulmonary artery rings were suspended on tensiometers in a balanced salt solution. A normoxic gas mixture was bubbled through the solution (21% O2, 5% CO2, 74% N2). Rings were preconstricted with phenylephrine, and the following mechanisms of pulmonary vascular smooth muscle relaxation were studied in a random order: (1) endothelial-dependent cyclic guanosine monophosphate-mediated (acetylcholine, 10( 9) to 10(-6) mol/L), (2) endothelial-independent cyclic guanosine monophosphate mediated (nitroprusside, 10(-9) to 10(-6) mol/L), and (3) beta-adrenergic receptor cyclic adenine monophosphate-mediated (isoproterenol, 10(-9) to 10(-6) mol/L). Separate rings were preconstricted with phenylephrine, and the gas was switched to a hypoxic mixture (0% O2, 5% CO2, 95% N2). After vasoconstriction to hypoxia reached a plateau, the response to the maximal effective dose of the above vasodilators (10(-6) mol/L) was determined in a random order. Statistical analysis was done with one-way analysis of variance with post hoc Bonferroni-Dunn correction. A p value of less than 0.05 was accepted as significant. RESULTS: Endothelial-dependent and -independent cyclic guanosine monophosphate-mediated relaxation was the same in normoxia and hypoxia. On the other hand, hypoxia inhibited beta-adrenergic receptor cyclic adenine monophosphate-mediated pulmonary vasorelaxation (97.5% +/- 2.5% versus 71.5% +/- 2.3% in hypoxia; p < 0.01). CONCLUSIONS: These data suggest that hypoxia selectively inhibits beta adrenergic cyclic adenine monophosphate-mediated pulmonary vasorelaxation. This dysfunction of the normal mechanism of pulmonary vasodilation may contribute to the pulmonary hypertension seen in adult respiratory distress syndrome. PMID- 7878540 TI - Recruitment of host CD8+ T cells by tumor-infiltrating lymphocytes and recombinant interleukin-2 during adoptive immunotherapy of cancer. AB - BACKGROUND: Previously we demonstrated that optimal doses of tumor-infiltrating lymphocytes (TIL) concomitant with recombinant interleukin-2 (rIL-2) effectively mediated complete tumor regression of murine 3-day pulmonary metastases. METHODS: In the present study we have investigated the contribution of the host immune response to the effectiveness of adoptive immunotherapy with TIL in combination with low-dose rIL-2. All experiments were performed in a murine pulmonary metastases model induced by intravenous injection of methylcholanthrene-induced sarcoma (MCA-105) cells into C57BL/6 mice. As a novel approach we used monoclonal antibody specific for CD4+ or CD8+ T cells to deplete the host of its T-cell subpopulations. RESULTS: Depletion of host CD8+ T cells 24 hours after tumor injection and 48 hours before TIL+rIL-2 treatment abrogated all antitumor activity of this type of immunotherapy and resulted in significant metastatic pulmonary disease (p < 0.001). In contrast, depletion of host CD4+ T cells did not alter the efficacy of TIL+rIL-2 treatment in tumor eradication. The loss of tumoricidal activity of TIL+rIL-2 treatment in a CD8+ T cell-depleted host could be overcome by adding back normal uneducated splenocytes 2 hours after TIL therapy (p < 0.001). In contrast, adding back CD8- CD4+ splenocytes to a CD8+ T cell-depleted host 2 hours after TIL+rIL-2 treatment resulted in significant pulmonary disease comparable to untreated animals. CONCLUSIONS: We conclude that the recruitment of host CD8+ T cells by adoptively transferred TIL+rIL-2 appears to be important for effective tumor eradication in this type of immunotherapy. PMID- 7878539 TI - Infrainguinal bypass in patients with end-stage renal disease. AB - BACKGROUND: This study was undertaken to evaluate the outcome of infrainguinal arterial reconstruction in a high-risk subset of patients with end-stage renal disease. METHODS: We reviewed the medical records of 44 patients requiring maintenance dialysis and undergoing 57 infrainguinal bypass procedures for limb salvage from 1986 to 1992. These included 16 (28%) femoropopliteal and 41 (72%) tibial or pedal bypasses with autogenous (82%), prosthetic (12%), or composite (6%) graft materials. The principal indications for operation were ischemic ulceration or gangrene (79%) and rest pain (21%). Angiographic evaluation most frequently showed single-vessel runoff (56%). Risk factors included age (mean, 63 years), diabetes (75%), hypertension (93%), coronary artery disease (52%), smoking (39%), previous myocardial infarction (20%), and contralateral amputation (18%). Infection was present in 22 limbs (39%). RESULTS: Early (30-day) surgical morbidity rate was 39%, including wound breakdown (19%), graft thrombosis (9%), and major amputation (4%). Perioperative mortality rate was 9%. Cumulative primary graft patency rates were 71% and 63%, secondary patency rates were 80% and 66%, and limb salvage rates were 70% and 52% at 1 and 2 years, respectively. Limb loss correlated most highly with the presence of preoperative infection (p = 0.036; log-rank method). Patient survival rate was 52% at 2 years. CONCLUSIONS: Life-table analysis confirms a poor life expectancy for this population but indicates that an acceptable level of limb salvage may be achieved with arterial reconstruction in properly selected patients. PMID- 7878544 TI - Is glutamine required for the trophic effect of epidermal growth factor? PMID- 7878545 TI - Randomized controlled trials in general surgery. PMID- 7878547 TI - Enlargement of splenic implants. PMID- 7878546 TI - Cystic medullary thyroid cancer. PMID- 7878537 TI - Insulin-like growth factor-I and insulin reduce leucine flux and oxidation in conscious tumor necrosis factor-infused dogs. AB - BACKGROUND: We have tested the hypothesis that insulin-like growth factor-I (IGF I) or insulin can prevent the protein catabolic effects of tumor necrosis factor (TNF). METHODS: After a 2-hour basal period TNF was infused (prime, 2.5 micrograms.kg-1; constant, 31.25 ng.kg-1.min-1) for 4 hours into conscious dogs to create the catabolic state. After 2 hours of TNF infusion either recombinant human IGF-I (n = 5) or recombinant human insulin (n = 5) was infused for an additional 2 hours. A third group (n = 5) received TNF alone for 4 hours. RESULTS: TNF infusion caused an increase in both glucose production, reflected by [6,6-d2]glucose tracer data, and net protein catabolism, reflected by both [1 13C]leucine and [15N2]urea tracer methods. IGF-I and insulin both significantly reduced the rates of appearance of leucine and leucine oxidation to a similar extent, resulting in the significant decrease in net protein catabolism. CONCLUSIONS: IGF-I and insulin can ameliorate the catabolic effects of TNF on protein and glucose metabolism equally effectively, although more IGF-I is required on a molar basis. PMID- 7878548 TI - Operative management of bile duct cancers. PMID- 7878549 TI - Inhaled corticosteroid therapy in children: an assessment of the potential for side effects. PMID- 7878551 TI - Control and prevention of tuberculosis in the United Kingdom: Code of Practice 1994. Joint Tuberculosis Committee of the British Thoracic Society. AB - BACKGROUND: The guidelines on control and prevention of tuberculosis in the United Kingdom have been reviewed and updated. METHODS: A subcommittee was appointed by the Joint Tuberculosis Committee (JTC). Each member of this group drafted one or more sections of the guidelines, and drafts were made available to all members of the group. In the course of several meetings drafts were altered and incorporated into a final text. The guidelines were approved by the full JTC and by the Standards of Care Committee of the British Thoracic Society. In revising the guidelines the authors took account of new published evidence and recent concerns about drug resistance and possible effects of HIV on tuberculosis. CONCLUSIONS: (1) All cases of tuberculosis must be notified. (2) A few patients need hospital admission. (3) Patients with positive sputum smears and sensitive organisms should be considered infectious until they have received two weeks' chemotherapy. (4) Treatment of all tuberculosis patients should be supervised by a respiratory physician employing standard medication guidelines and monitoring compliance at least monthly. (5) Health care workers at risk should be protected by BCG vaccination and appropriate infection control measures, and evidence of infectious tuberculosis should be sought among prospective NHS staff, school teachers, and others. (6) Prison staff should be protected. (7) Tuberculosis should be considered in the elderly in long stay care with persistent chest symptoms. (8) Contact tracing should be vigorously pursued with chemoprophylaxis, BCG vaccination, or follow up where applicable. (9) Entrants to the UK from high risk countries (tuberculosis incidence more than 40/100,000 population per year) should be screened. (10) BCG vaccination should be offered where appropriate but not in subjects with known or suspected HIV infection. (11) The local organisation of tuberculosis services should be strengthened and should include adequate nursing and support staff. (12) Contracts between purchasers and providers should specify management of tuberculosis in line with this and other JTC guidelines. PMID- 7878550 TI - Role of viral infections in the inception of asthma and allergies during childhood: could they be protective? PMID- 7878552 TI - Respiratory symptoms of rural Fijian and Indian children in Fiji. AB - BACKGROUND: Significant ethnic differences exist in the respiratory morbidity of children in the Fiji Islands. Indian children have higher national hospital admission rates for asthma whereas Fijian children have higher admission rates for pneumonia. In Suva City the prevalence of wheeze is similar in Fijian and Indian children, productive cough is more common in Fijians, and bronchial hyperresponsiveness is more common in Indians. This study was undertaken to see whether ethnic differences in national hospital admission rates are reflected in the prevalence of respiratory symptoms in rural children. METHODS: A respiratory symptoms questionnaire in three languages with known repeatability was returned by 487 (98.2%) of 496 class 4 primary school children with a mean age of 9.3 years living in Nausori District, an agrarian region with a climate similar to Suva City. RESULTS: The prevalence of one or more episodes of wheezing in the last 12 months was similar in Fijians (19.8%) and Indians (19.4%). However, 8.9% of Indian children had experienced four or more episodes of wheeze in the last 12 months compared with only 2.9% of Fijian children. Productive cough on most mornings occurred more frequently in Fijians (35.8%) than Indians (23.9%), but this difference was not significant after controlling for the presence of a smoker in the home. CONCLUSIONS: This study provides the first evidence that frequent wheeze (four or more episodes in the last 12 months) is more prevalent in Indian than Fijian children. The higher prevalence of productive cough in Fijian children may be related to exposure to smoking in the home. PMID- 7878553 TI - Asthma, allergy, and atopy in three south-east Asian populations. AB - BACKGROUND: Whilst many recent reports have suggested a rise in the prevalence of asthma and allergic disease in Western countries, little is known about the epidemiology of these common conditions in south-east Asia. This study compared the prevalence of asthma and allergic disease amongst secondary school students in three south-east Asian populations--Hong Kong, Kota Kinabalu in Malaysia, and San Bu in China--and investigated the associations with atopy and family history. METHODS: Secondary school students were given standard questionnaires on respiratory and allergic symptoms for completion by parents with response rates of 89.2% in Hong Kong (611 male, 451 female; mean (SD) age = 13.9 (1.8 years), 87.6% in Kota Kinabalu (134 male, 275 female; 15.5 (2.1) years), and 98.6% in San Bu (492 male, 245 female; 16.4 (1.8) years). Skin tests were performed in a subsample of students to determine atopic status. RESULTS: The respective prevalence (and 95% CI) for hayfever, eczema, and wheeze or asthma were 15.7% (13.5, 17.9), 20.1% (17.7, 22.5), 11.6% (9.3, 13.9) in Hong Kong, 11.2% (8.2, 14.3), 7.6% (5.0, 10.1), 8.2% (5.5, 10.9) in Kota Kinabalu, and 2.1% (1.2, 3.1), 7.2% (5.4, 9.1), 1.9% (0.7, 3.1) in San Bu. Atopy was common and was present in 49.0-63.9% of subjects in the three populations. Dust mite and cockroach were the commonest allergens that gave positive reactions in 42.8-60.5% and 25.7-35.9% of students respectively. A higher proportion of students in Hong Kong had severe degree of reactivity on skin test than the other two populations. Family history was associated with asthma and allergic symptoms in the three populations conferring a 3-80-fold increase in risk to family members and was a stronger predictor for asthma and allergy than atopy. CONCLUSIONS: Prevalence of asthma and allergic disease is low compared with Western countries, but considerable differences exist between the three south-east Asian populations despite similar rates of atopy. Asthma and allergic disease are more strongly associated with family history than atopy, which suggests that genetic and environmental factors common to the family, other than aeroallergen sensitisation, are important in the pathogenesis of asthma and allergy in the region. PMID- 7878554 TI - Airways inflammation in subjects with chronic bronchitis who have never smoked. AB - BACKGROUND: Smoking is the single most common cause of chronic bronchitis but the disease can also occur in non-smokers. Alterations in the lung responsible for the disease, such as oxidant/antioxidant and protease/antiprotease imbalance, have been investigated in smokers. The aim of our study was to evaluate local cellular and soluble factors (albumin, immunoglobulins, proteases, alpha 1 antitrypsin, and transferrin) that may be involved in the development of chronic bronchitis in subjects who have never smoked. METHODS: Sixteen clinically stable patients with chronic bronchitis who had never been smokers were studied and 17 healthy non-smokers served as controls. All subjects underwent bronchoalveolar lavage (BAL). Total and differential cell counts and concentrations of the main proteins (albumin, immunoglobulins, complement fractions, alpha 1-antitrypsin, and transferrin) were measured. Elastase-like activity was assessed in cells and supernatants. To estimate the oxidant burden the release of superoxide anion (O2 ) from native cell populations was evaluated. RESULTS: Recovery of BAL fluid was reduced in older individuals in both the chronic bronchitis and control groups. There was no difference in total cell count, but neutrophil percentage count was higher in those with chronic bronchitis (median (range) 3.5 (1.6-14.2)) than in controls (1.3 (0.5-3.7)). These differences were most pronounced in the first recovery, representative of the bronchial lavage. There was no difference in bronchial epithelial cells. Total proteins and albumin levels were comparable and IgG, IgA, IgM, C3, C4, transferrin and alpha 1-antitrypsin values standardised to albumin did not show any significant differences. No differences in elastase-like levels in supernatants were detected. In cell lysates elastase-like activity x 10(7) cells (macrophages+neutrophils) was increased in patients with chronic bronchitis (0.25 (0.06-4.3) compared with controls 0.08 (0.03-0.9) micrograms PPEeq). The release of O2- both at baseline and after opsonised zymosan phagocytosis did not show any differences. Correlation analysis between FEV1 and BAL fluid data showed a negative correlation only with neutrophils/ml. CONCLUSIONS: Clinically stable non-smokers with chronic bronchitis show no alterations of local immune components, oxidant burden, and free elastase-like activity in BAL fluids, while the content of elastase-like activity in phagocytic cells is increased. As in smokers, bronchial neutrophilia is the most significant cellular modification which correlates with the degree of airflow obstruction. PMID- 7878555 TI - Prevalence and risk factors for chronic bronchitis in Pelotas, RS, Brazil: a population-based study. AB - BACKGROUND: Chronic bronchitis causes high morbidity and mortality throughout the world. It is basically a preventable disease. However, few population based studies of chronic bronchitis have been carried out in less developed countries. METHODS: A population based cross sectional survey was conducted to determine the prevalence of chronic bronchitis and associated risk factors in an urban area (Pelotas) of southern Brazil. 1053 subjects aged 40 years and over (90.3% of eligible subjects) were interviewed using the ATS-DLD-78 questionnaire. RESULTS: Of the subjects interviewed 12.7% were classified as having chronic bronchitis. In univariate analyses a significant increase in the relative odds of chronic bronchitis was seen in men (OR = 2.17, 95% CI 1.50 to 3.13), low family income (OR = 2.60, 95% CI 1.47 to 4.47 for lowest quartile), low schooling (OR = 4.65, 95% CI 2.36 to 9.18 for those with no schooling), smoking habits (OR = 6.92, 95% CI 4.22 to 11.36 for smokers of 20 or more cigarettes per day), high occupational exposure to dust (OR = 2.48, 95% CI 1.56 to 3.94), inadequate housing (OR = 2.09, 95% CI 1.22 to 3.58), high level of indoor air pollution (OR = 1.86, 95% CI 1.16 to 2.99), and reported childhood respiratory illnesses (OR = 2.08, 95% CI 1.25 to 3.49). Multiple logistic regression resulted in the identification of the following independent risk factors: family income (OR = 1.99, 95% CI 1.04 to 3.81 for subjects in the lowest quartile compared with those in the highest quartile), schooling (OR = 5.60, 95% CI 2.52 to 12.45 for subjects with no schooling compared with those with nine or more years), smoking (OR = 8.10, 95% CI 4.46 to 14.71 for smokers of 20 or more cigarettes per day compared with non-smokers), and history of major respiratory illnesses in childhood (OR = 2.16, 95% CI 1.20 to 3.85). CONCLUSIONS: Low family income, poor schooling, smoking, and childhood respiratory illnesses were significantly associated with chronic bronchitis. PMID- 7878556 TI - Nasal ventilation in acute exacerbations of chronic obstructive pulmonary disease: effect of ventilator mode on arterial blood gas tensions. AB - BACKGROUND: There are no controlled trials of the use of different modes of nasal intermittent positive pressure ventilation (NIPPV) in patients with exacerbations of chronic obstructive pulmonary disease (COPD). This study describes the effect on blood gas tensions of four different modes of nasal ventilation. METHODS: Twelve patients with acute exacerbations of COPD were studied (mean (SD) FEV1 0.59 (0.13) l, PaO2 (air) 5.10 (1.12) kPa, PaCO2 9.28 (1.97) kPa, pH 7.32 (0.03)). Each patient underwent four one-hour periods of nasal ventilation in randomised order: (a) inspiratory pressure support 18 cm H2O; (b) pressure support 18 cm H2O+positive end expiratory pressure (PEEP) 6 cm H2O (IPAP+EPAP); (c) continuous positive airway pressure (CPAP) 8 cm H2O; and (d) volume cycled NIPPV. Arterial blood samples were obtained before each period of ventilation and at one hour. RESULTS: Pressure support, CPAP, and volume cycled NIPPV all produced significant improvements in PaO2; there was no difference between these three modes. The change in PaO2 with IPAP+EPAP did not reach statistical significance. None of the modes produced significant changes in mean PaCO2; patients with higher baseline levels tended to show a rise in PaCO2 whereas those with lower baseline levels tended to show a fall. CONCLUSIONS: Although PaO2 improved in all patients there are differences in efficacy between the modes, while the changes in PaCO2 were variable. The addition of EPAP conferred no advantage in terms of blood gas tensions. PMID- 7878557 TI - Treatment of nocturnal asthma with nedocromil sodium. AB - BACKGROUND: The association of nocturnal asthma symptoms with a diurnal increase in inflammatory activity suggests a role for anti-inflammatory therapy in nocturnal asthma. METHODS: Fifty patients with asthma with nocturnal symptoms entered a randomised, double blind, placebo controlled, crossover study. After a two week baseline period patients received nedocromil sodium (4 mg) or placebo four times daily. After eight weeks of treatment patients crossed to the alternative treatment for a further eight weeks. Symptom severity was recorded on a scale of 0-4 and inhaled bronchodilator use and peak flow (PEFR) were also recorded daily by the patients. Asthma severity, pulmonary function (FEV1, PEFR, FVC), and adverse events were recorded at clinic visits (baseline and after four and eight weeks of treatment). Global effectiveness was rated by clinician and patient, and treatment preference was recorded. RESULTS: Efficacy was assessed from data from 28 patients. Night-time asthma (mean (SE) difference between nedocromil sodium and placebo: -0.52 (0.13)), total nocturnal symptom severity defined as night-time asthma plus morning tightness (-0.72 (0.20)), and night time bronchodilator use (-0.62 (0.23)) were reduced with nedocromil sodium compared with placebo treatment during the primary efficacy period (weeks 5-8) and during weeks 1-4 (-0.36 (0.12), -0.63 (0.20), and -0.55 (0.28), respectively). Morning and evening PEFR values improved slightly--but not significantly--compared with placebo. Patient and clinician opinions favoured nedocromil sodium treatment. Daytime asthma, daytime cough, and clinic assessment of asthma severity (secondary efficacy variables) were improved with nedocromil sodium treatment; day-time bronchodilator use and clinic pulmonary function were not. CONCLUSIONS: Nedocromil sodium was more effective than placebo in reducing nocturnal symptoms of asthma and bronchodilator use in this group of patients. PMID- 7878558 TI - Comparison of terbutaline and placebo from a pressurised metered dose inhaler and a dry powder inhaler in a subgroup of patients with asthma. AB - BACKGROUND: Reversibility after administration of an inhaled bronchodilator is not always demonstrable in patients with asthma. Bronchodilator aerosol-induced bronchoconstriction has also been reported to occur in some patients. METHODS: Fifteen selected patients showing < 10% improvement in forced expiratory volume in one second (FEV1) when tested with four doses of salbutamol (0.1 mg/dose) or terbutaline (0.25 mg/dose) from a pressurised metered dose inhaler (MDI) participated in two randomised, double blind studies. They received 2.0 mg terbutaline (4 x 2 doses of 0.25 mg) or a corresponding placebo from an MDI connected to a 750 ml spacer, and 1.0 mg (2 x 0.5 mg) terbutaline or placebo from a multidose dry powder inhaler free of additives (Turbohaler). RESULTS: Inhalation of placebo MDI resulted in a mean (SD) decrease in FEV1 of 20.5 (14.1)% (range -42.9% to +2.6%). In 14 patients inhalation of 2.0 mg terbutaline MDI with spacer resulted in < 10% improvement (mean increase 3.1 (6.0)%). One mg of terbutaline via a Turbohaler resulted in improvements in FEV1 of > 15% in eight patients (mean increase 16.0 (9.7)%). The improvement was < 10% in four patients. Use of placebo Turbohaler did not affect airway calibre (mean change 0.2 (2.9)%). CONCLUSIONS: Additives of MDIs may cause bronchoconstriction in some patients with asthma. In these patients inhalation from a pressurised metered dose inhaler is more likely to decrease the bronchodilator response than inhalation from an additive-free inhaler. The frequency of this phenomenon is unknown. PMID- 7878559 TI - Serum interleukin 5 concentrations in atopic and non-atopic patients with glucocorticoid-dependent chronic severe asthma. AB - BACKGROUND: Interleukin (IL)-5 is thought to play a part in asthmatic bronchial mucosal inflammation and is a potential therapeutic target. Detectable serum IL-5 concentrations have been found previously in a proportion of patients with acute severe asthma, but not in the same patients following oral glucocorticoid therapy or in normal controls. A study was undertaken to investigate whether or not IL-5 is detectable in the serum of patients with glucocorticoid-dependent chronic severe asthma. METHODS: Serum concentrations of IL-5 were measured in 29 patients with stable oral glucocorticoid-dependent chronic severe asthma (mean PEFR 59.7% predicted) and seven normal controls using a specific enzyme-linked immunoassay calibrated with recombinant human IL-5 standards (lower limit of sensitivity 40 pg/ml). RESULTS: Interleukin 5 was detectable in the serum of 15 of the 29 patients at a median concentration of 150 pg/ml (range 40-690), but was undetectable in the serum of all the control subjects. The patients with detectable serum IL-5 concentrations did not differ from those with undetectable concentrations in terms of atopic status, disease severity (percentage predicted PEFR or FEV1), prednisolone dosage, serum IgE concentrations, or peripheral eosinophil count. CONCLUSIONS: Interleukin 5 is detectable in the serum of a proportion of both atopic and non-atopic patients with chronic severe asthma, and concentrations in these patients were higher than in normal controls. These observations are compatible with the hypothesis that IL-5 release occurs in these patients during a period of stable asthma despite systemic glucocorticoid therapy. PMID- 7878560 TI - Potentiation of diaphragmatic twitch after voluntary contraction in normal subjects. AB - BACKGROUND: Skeletal muscle twitch responses may be transiently increased by previous contractions, a phenomenon termed twitch potentiation. The aim of this study was to examine the extent and time course of diaphragmatic twitch potentiation and its relationship to both the magnitude and duration of the preceding voluntary diaphragmatic contraction. METHODS: Twitch transdiaphragmatic pressure (PDI) was measured in six normal subjects, before and after voluntary diaphragm contractions of 100%, 75%, 50%, and 25% of maximum PDI (PDImax) sustained for five and 10 seconds. RESULTS: Twitch PDI was significantly increased after 100%, 75%, and 50% contractions. Following maximal contractions sustained for 10 seconds the mean increase in twitch PDI was 52%. Following 50% contractions sustained for five seconds the mean increase in twitch height was 28%. In all runs twitch PDI returned to rested levels within 20 minutes. CONCLUSIONS: Twitch potentiation can be substantial, even following submaximal contractions, and must be taken into account when twitch pressure is used to assess diaphragm contractility. PMID- 7878561 TI - Single lung alveolar volume and gas transfer: effect of expansion of the other lung. AB - BACKGROUND: Temporary occlusion of one mainstem bronchus permits measurement of single lung function. A previous study suggested that the volume at which one lung is occluded may influence the expansion of the other. The effect of ipsilateral occlusion volume on the contralateral effective alveolar volume (VA, EFF,SL), inspired volume (VI,SL), single breath estimated residual volume (RVSB,SL), carbon monoxide (CO) transfer (TLCO,SL) and transfer coefficient (KCO,SL) has been examined. METHODS: Single breath measurements of CO transfer were made in duplicate in 12 healthy subjects aged 19-44 years, without and during occlusion of one mainstem bronchus by a balloon at RV and at total lung capacity (TLC). RESULTS: Mean VA,EFF,SL, VI,SL, and TLCO,SL were lower during occlusion at RV than during occlusion at TLC (2.84 v 3.26 l; 2.18 v 2.54 l; and 4.70 v 5.51 mmol/kPa/min respectively). RVSB,SL was independent of occlusion volume and KCO,SL not different from the KCO of both lungs (KCO,BL). Single lung values during occlusion at TLC were fairly reproducible and were, except for KCO,SL, approximately half the values for both lungs. During occlusion at RV the second TLCO,SL and KCO,SL were lower than the first. CONCLUSIONS: Occlusion of one lung permits reliable determinations of gas transfer indices of the other, provided the lung is occluded at TLC. Occlusion at RV significantly reduces VA,EFF,SL, and hence TLCO,SL, but does not affect KCO,SL of the other lung. PMID- 7878562 TI - C-type natriuretic peptide levels in cor pulmonale and in congestive heart failure. AB - BACKGROUND: C-type natriuretic peptide (CNP) is a recent addition to the family of natriuretic peptides which includes atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Whilst the levels of ANP and BNP are increased in conditions such as congestive heart failure and cor pulmonale, abnormal levels of CNP in these conditions have not been reported. METHODS: Plasma levels of CNP were measured by specific radioimmunoassay in 12 young normal controls, 12 elderly normal controls, 12 patients with NYHA grade III-IV congestive heart failure, and in 16 patients with hypoxaemic cor pulmonale. RESULTS: Mean (SE) plasma levels of CNP were similar in young normal controls (0.46(0.03) pmol/l), elderly normal controls (0.43(0.05) pmol/l), and in patients with congestive heart failure (0.33(0.2) pmol/l). In patients with cor pulmonale, however, plasma levels of CNP were raised (1.39(0.27) pmol/l) 3.2-fold compared with age-matched controls. CONCLUSIONS: In cor pulmonale the increased plasma levels of CNP were not as great as the previously observed increases in levels of ANP (5.6-fold) or BNP (18.5-fold) in comparable patients. CNP may therefore be less important than ANP or BNP as a circulating counter-regulatory peptide in conditions of overactivity of the renin angiotensin system. PMID- 7878563 TI - Effect of exercise on the nasal transmucosal potential difference in patients with cystic fibrosis and normal subjects. AB - BACKGROUND: Normal subjects have a negative nasal transmucosal potential difference (TPD) at rest which becomes more negative with exercise. Patients with cystic fibrosis have a more negative resting nasal TPD than controls. The present study was designed to determine the effects of exercise on the TPD of patients with cystic fibrosis. METHODS: Seven subjects with cystic fibrosis and seven control subjects had their usual TPD measured at rest, and during and after a 12 minute period on an exercise bicycle designed to produce a pulse rate of 80% of their maximum predicted value. RESULTS: The normal subjects developed a more negative nasal TPD during exercise which returned towards normal at the completion of the rest period. The patients with cystic fibrosis had higher resting values which became less negative during exercise. At the end of the exercise period there was no difference between the two groups. At the end of the recovery period the results for the patients with cystic fibrosis had returned to their resting values. CONCLUSIONS: Exercise reduces the abnormally high resting values for nasal TPD in patients with cystic fibrosis. Elucidation of the mechanism for this change may help to produce functional improvement for patients with this disease. PMID- 7878564 TI - Contribution of multiple inert gas elimination technique to pulmonary medicine. 5. Ventilation-perfusion relationships in acute respiratory failure. PMID- 7878566 TI - Lymphangioma of the oesophagus: a case report and review of the literature. AB - Lymphangioma of the oesophagus is exceedingly rare. Seven cases (including our present case) have been reported in the world and are reviewed. PMID- 7878565 TI - Studies using radiolabelled aerosols in children. PMID- 7878568 TI - Respiratory failure with diffuse patchy lung infiltrates: an unusual presentation of squamous cell carcinoma. PMID- 7878567 TI - Pleural mesothelioma associated with non-Hodgkin's lymphoma. AB - Occupational exposure to asbestos has been associated with an increased incidence of lung and gastric cancers, mesotheliomas, and myelolymphoid malignancies. A new observation of a patient with indirect exposure to asbestos who developed mesothelioma and plasmacytoid lymphocytic non-Hodgkin's lymphoma is described. This report and the previously described stimulation of B lymphocytes by asbestos suggests that the association of mesothelioma with lymphoid and plasma cell malignancies is not merely a coincidence. PMID- 7878569 TI - Thoracoscopic treatment of postoperative chylothorax after coronary bypass surgery. AB - Chylothorax after sternotomy for aortocoronary bypass surgery is a rare but serious complication. To avoid lateral thoracotomy a left sided thoracoscopy was performed and the site of the leakage was immediately found and successfully clipped. PMID- 7878570 TI - Massive cerebral infarction after completion pneumonectomy for pulmonary torsion. AB - A case of lower lobe torsion after left upper lobectomy is reported which was complicated by a cerebral infarction after completion pneumonectomy. Results of a small survey in Flanders revealed two additional cases of pulmonary torsion after lobectomy. PMID- 7878571 TI - Lung structure and function in cigarette smokers. PMID- 7878572 TI - Chronic respiratory questionnaire. PMID- 7878573 TI - Bordetella bronchiseptica pneumonia. PMID- 7878574 TI - Impact of HIV on tuberculosis in developing countries. PMID- 7878575 TI - Ultrasound assessment of diaphragmatic movement. PMID- 7878576 TI - [Advantages of meta-analysis of clinical trials]. PMID- 7878577 TI - [Problems raised by the conducting and interpretation of meta-analysis]. PMID- 7878578 TI - [The dilemma of the prescribing physician faced with meta-analyses. Example of presumed digestive toxicity of corticoids]. PMID- 7878579 TI - [Treatment of extra-membranous glomerulonephritis with immunosuppressive agents or difficulties of meta-analysis in nephrology]. PMID- 7878580 TI - [Value and limits of conventional or cumulative meta analysis in obstetrics and gynecology]. AB - The authors describe some situations where meta-analyses would have been of great benefit if they have been done or sufficiently published. They emphasize several problems ensued by this new method: if possible, meta-analyses have to be done each time a new trial is analysed, according to a precise method. Cumulative meta analysis should rely on a regular and prospective registration of clinical trials. In all cases, meta-analyses should be available to a large number of physicians, in the main interest of patients. PMID- 7878581 TI - [Critical examination of scoring systems in therapeutic trials]. AB - Scoring systems give a check-list and methodological informations which have to be found in controlled therapeutic trials reports and papers. These systems try to quantify each item to give a global score. The Chalmer's list is the most wellknown. It allows a balance in scoring taking in account the quality of the endpoints. Other lists are more simple. Many check-lists allow the scoring of the methodological design or the statistical analysis. In all systems the major methodological points are: the randomization, the description of the population, the double blind, the estimation of the sample size, the handling of withdrawal and drop out, the major endpoint, the patients follow-up, the statistical analysis and the data presentation. All these scoring systems have several limits: the quantitative evaluation of each item is subjective and the point scoring has never been validated, some scoring systems are old and don't integrate new methodological methods, the scores never included the clinical interest of the trial, some items are questionable, others are forgotten (intention to treat analysis, steering comity...). Scoring systems allow a control of the methodological quality of clinical trials but don't include the clinical or scientific interest of the study. These systems are a useful methodological tool for publication process in medical journals and for new drugs authorization. The evaluation by authors themselves of the quality of their papers using a standardized scoring system could clarify the reviewers decisions. PMID- 7878582 TI - [Consensus conference: methodology and contribution]. AB - A consensus conference is a method used to evaluate a medical process and to elaborate practice guidelines. The goal of consensus conference is to obtain the best possible outcomes for patients. The guidelines are written by a multidisplinary jury which analyses scientific datas and clinical practices. Consensus conference don't resolve all medical problems. It's a good evaluation method for the topics where there are non medical sides, inappropriate medical options or different clinical practices in spite of sufficient scientific datas. Consensus conference use three distinct groups: organization committee, jury and experts. The lectures of the experts and the guidelines must distinguish and clarify which is scientifically proved. Use of biomedical databases and critical analysis of biomedical articles are useful. Practice guidelines must be clear, precise, explicit and useful for clinical practices. Measurement of the real usefulness of consensus conference is difficult: it's the problem of the impact of guidelines on care. Usually it could be realized by survey of clinical practices or drugs consuming. The impact will be better with a large use of media, dissemination of the guidelines in the medical faculties and during professional workshops. PMID- 7878583 TI - [Limitations of consensus conferences]. PMID- 7878584 TI - [Nursing care evaluation, how to measure it and why?]. AB - Quality of care assessment is based on three main prerequisites: to describe precisely patients or case-mix, to measure the level of care, to evaluate the outcomes and finally to consider the relationships between these parameters. Indicators to measure the level of nurses' workload have been developed from different concepts and methodologies: The range of nurses' activities is very wide, such as cares achieved in the presence of patient, cares achieved after medical prescription or specific nurse cares, administrative tasks, research activities, etc. Indicators may take into account a more or less important part of this field, but most of them are usually focused on patient's care. The value of each parameter may be a calculated coefficient or a time unit. If one considers the time as the best unit to measure the intensity of work, it is also an underlying concept to differentiate the actual time, obtained by timing, from the required time, necessary to achieve correctly the action. In the same way, required cares are also the best to consider. Indeed measuring required time for required cares is necessary to reach quality aim. The nurses' workload may be directly calculated with a specific indicator or indirectly estimated from a severity or disability scoring system. The selection of the indicator depends of the purpose of the evaluation process. If the question is to improve and develop quality of care and professional practices, the indicator has to take into account the required cares. The PRN system (Project de Recherche en Nursing) developed in Canada is probably the reference indicator. However this score is complex and cannot be daily used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878585 TI - [Methods of antiarrhythmic drug evaluation in man]. AB - Antiarrhythmic drugs (AA) are useful in some critical situations but their use remains questionable. Evaluation of their efficacy and possible side effects required accurate knowledge of various methods. ECG gives relevant informations on the conduction intervals alterations caused by AA. Holter monitoring allows evaluation of the efficacy and/or proarrhythmic effects throughout 24-48 hour periods provided that spontaneous variability is taken into account. Ambulatory sequential loop ECG allows a longer monitoring of treatment in patients with symptomatic arrhythmias. Provocative electrophysiological testings give good evaluation of AA efficacy in some supraventricular or ventricular arrhythymias but predictivity of efficacy or proarrhythmic effects is sometimes problematical. Use of effort testing is limited to evaluation of antiarrhythmic effects of drugs in major dysrythmias and in some frequency-dependent dysrythmias, but this technique allows also detection of proarrhythmic incidence in those extremely altered autonomic nervous system tone. Other techniques of evaluation (Signal averaged ECG, automatic implantable cardiovecter defibrillator with holter monitoring, drug plasma concentration monitoring) are still under discussion. PMID- 7878586 TI - [Digoxin and angiotensin-converting enzyme inhibitors in the treatment of chronic congestive heart failure]. AB - Several controlled studies with the best methodology had showed that digoxin improves the symptoms of patients with chronic heart failure and sinus rhythm, whose ventricular systolic function is impaired. The Proved and Radiance studies show that in patients receiving diuretics and digoxin, or angiotensin-converting enzyme (ACE) inhibitors, diuretics and digoxin, the withdrawal of digoxin results in clinical deterioration and worsening of exercise tolerance. In addition to an inotropic action, digitalis exerts effects in the neurocardiovascular axis, produces reduction in plasma norepinephrine, renin, aldosterone, vasopressin activity and restores a more normal sympathetic-parasympathetic autonomic balance and baroreceptor function. ACE inhibitors reduce mortality, improve symptoms and exercise tolerance in patients with chronic heart failure in class IV (Consensus I trial), in class II and III (SOLVD, treatment trial) and prevent the development of heart failure in asymptomatic patients with ejection fraction < 35% (SOLVD, prevention trial). When ACE inhibitors are administered per os, more than 3 days after acute myocardial infarction they reduce mortality, severe heart failure, re-hospitalization, and induce an unexpected reduction of recurrent myocardial infarction (SAVE trial). However, the early administration, within 2 hours after the onset of chest pain, of ACE inhibitors by intravenous infusion, does not improve survival; the hypotension may be responsible of increased mortality (Consensus II trial). PMID- 7878587 TI - [Beta-blockers and heart failure]. AB - Several studies have suggested that beta-blockade could provide functional benefit in heart failure, suggesting a deleterious role for the compensatory sympathetic stimulation. Beta-blockade induced benefit could result from either antagonism of any myocardial beta-adrenergic stimulation or on the opposite a paradoxical cardiac beta-adrenergic responsiveness secondary to beta-adrenergic receptor up-regulation. Two recently completed large scale multicentric placebo controlled studies, the MDC trial with metoprolol and CIBIS with bisoprolol, have confirmed that beta-blockade could functionally improve patients with heart failure. The observed survival improvement in non ischemic patients was observed only in the CIBIS trial. Such a result must be confirmed with additional studies. PMID- 7878588 TI - [Evaluation of therapeutic strategies: apropos of antidepressive agents]. PMID- 7878589 TI - [Analysis and evaluation of strategies of drug treatment of pain]. PMID- 7878590 TI - [The association of two active principles]. PMID- 7878591 TI - [Methods of drug evaluation in chronic bronchitis]. PMID- 7878592 TI - [Long term evaluation of treatments of depressive states and anxiety disorders]. PMID- 7878593 TI - [Methodology and evaluation of blood pressure variability]. PMID- 7878594 TI - Individual differences in the in vitro response to cyclosporin A (CsA): possible heterogeneity in the involvement of the CD28-B7/BB1 pathway. AB - Differences in the response of graft recipients to the immunosuppressive effect of cyclosporin A (CsA) represent a major factor of allograft acceptance. Response to CsA was investigated in vitro in 59 healthy subjects by measuring the inhibition of lymphocyte proliferation and interleukin-2 (IL-2) production. Marked differences were found comparing individuals: 61% of the subjects responded with half inhibitory doses ID50 < 200 ng/ml (responder group), 20% with ID50 within 200-400 ng/ml (intermediate responder) and 19% were non responder with ID50 > 400 ng/ml and sometimes over 1,000 ng/ml. To explain these differences, the CD28-B7, co-stimulatory pathway for T-cell activation was explored since it is the only CsA-resistant pathway known so far. Both responder and non responder individuals showed increased proliferative response and IL-2 secretion by co-stimulation with CD3 and CD28, resulting in increased ID50 by a similar factor. The percentage of CD28+ cells within T-lymphocytes varied markedly among subjects (48.5 +/- 28.9% of the CD8+ cells). However we could not correlate the inter-individual variation of sensitivity to CsA to the size of the CD8+CD28+ T cell subset nor to divergent response to CD3 and CD28 co-stimulation. PMID- 7878595 TI - [Relationship between hepatic cytochrome P-450 3A and acute cyclosporine toxicity in liver transplantation]. AB - Despite the availability of whole blood cyclosporine assays, the different response of individual patients to its administration following transplantation continue to pose clinical problems, particularly in respect of toxicity. The aim of this study was to know if the inter-individual variations in the hepatic concentration of cytochrome P-450 3A, that metabolizes cyclosporine into several metabolites with very limited immunosuppressive activity, could be associated with cyclosporine toxicity. 59 consecutive liver transplant recipients were studied. Immunosuppression was with cyclosporine, azathioprine and methylprednisolone. The relative concentration of P-450 3A was assessed by immunoblot analysis using a specific monoclonal antibody on liver graft biopsy. Twelve patients experienced toxic neurological and renal complications. Six of these patients had cyclosporine levels in the therapeutic range. There was an excellent correlation between the occurrence of complications and cyclosporine whole blood levels (P < 10(-4), the first day post-op after a standard dose of cyclosporine (1 mg/kg). Cytochrome P-450 3A hepatic content assessed in a groups of 34 patients exhibited a 10-fold variation (m = 94 +/- 47 AU (Arbitrary Units)/mg). Eight of these patients who developed cyclosporine toxicity had a lower graft P-450 3A levels (m = 52 +/- 19 AU/mg, P = 3.10(-4), cf. patients with no toxicity). This highlights the importance of the first dose of cyclosporine and indicates that cytochrome P-450 3A can provide information which should allow individualized immunosuppression with cyclosporine maintaining therapeutic levels but avoiding toxicity in susceptible individuals. PMID- 7878596 TI - [Therapeutic information: how to transmit current scientific data. Group VALIDATA]. AB - The information on therapeutics is moving at a high path for various causes. Now, tools for informing correctly the prescriber do exist. However, they require the operation of suitable structures. The mainstem of the system consists of an intermediary which should comply with appropriate rules. It will work from an exhaustive collection of pertinent information. This will allowed by the extensive use of literature data banks and clinical trial registries kept with the help of international collaboration. It will rank the strength of evidence of the collected data according to their internal validity. It will elaborate overviews from validated data obtained from meta-analysis, and messages readily readable by the users, and accessible whenever needed. Overviews will be used to set up guidelines, references, editorials... Data banks will be accessible to researchers, teachers, officers concerned by health care. PMID- 7878597 TI - [Controlled randomized trials of pharmaceutic aids for smoking cessation. Results and perspectives]. AB - In several cases tobacco smoking fulfills criteria for drug dependence. Withdrawal symptoms after smoking cessation are considered the main cause of relapses. We reviewed results of controlled clinical drug trials (testing nicotine patch, nicotine nasal spray, clonidine, buspirone and doxepin) in smoking cessation. End of treatment quit rates at 3 months with nicotine patch vary between 14% and 39% and one year quit rates between 9% et 26%. Studies with nasal nicotine spray give similar results but nicotine spray is less well tolerated than nicotine patch. The therapeutic effectiveness of nicotine patch seems to be insufficient and there is only one report of long term (> 1 year) results which should be the main goal of treatments used in smoking cessation. A therapeutic approach with psychotropic drugs founded on a better characterization of dependent smokers' psychopathology (depression, anxiety...) may be a more promising research field. PMID- 7878598 TI - [Pharmacokinetics of low-dose lithium in healthy volunteers]. AB - The pharmacokinetics of lithium in healthy volunteers receiving low doses of lithium as Lithium Oligosol by sublingual route were investigated in two randomized crossover studies (lithium vs placebo) with a two week wash-out period. In the first study, 8 volunteers received a single dose (1.68 mg) of lithium and in the second 8 another volunteers received repetitive doses of lithium (0.56 mg twice a day) during 11 days. The plasma concentration of lithium was determined by an electrothermal atomic absorption spectrometry. The plasma concentrations of lithium measured during the placebo period were about 1 microgram/L, the peak concentration was 99.4 +/- 22.2 micrograms/L in the single dose study and 49.6 +/- 5.4 micrograms/L in the multiple doses study. In this last one, the residual plasma levels of lithium were between 20 and 25 micrograms/L. The pharmacokinetics parameters measured were: T1/2 = 22.6 +/- 3.1 h; Vd/F = 0.70 +/- 0.09 L/kg and Cl/F = 1.53 +/- 0.12 L/h. The plasma concentrations of lithium are strictly dependent on intake from food or drugs. PMID- 7878599 TI - [Pseudomembranous colitis caused by antibiotic therapy. Results of a survey of the patient material from the praxis of 900 gastroenterologists]. AB - A retrospective study conducted by interviewing French gastroenterologists was performed with the objective of evaluating the incidence and etiology of pseudomembranous colitis in cases where the diagnosis has been confirmed by coloscopy. This study allowed to collect data on 878 pseudomembranous colitis observed by 438 gastroenterologists within 6 months. It shows evidence of the importance of various antibiotics in the etiology of pseudomembranous colitis (89% of the identified cases). The following is the list of antibiotics or antibiotic classes, in increasing order of their association with the development of pseudomembranous colitis: macrolides which are very rarely associated, a group represented by cefaclor, cefuroxime axetil and cyclins, which are rarely associated, a third group constituted by amoxicillin, ofloxacin and trimethoprim sulfamethoxazole which appears to be 2 to 3 times more frequently associated than the previous group, and a fourth group of antibiotics, represented by cefixime and the association amoxicillin-clavulanic acid, which is 7 times more frequently associated than antibiotics of the second group. PMID- 7878600 TI - [Pyridoxine neuropathies. Review of the literature]. AB - Daily needs of vitamin B6 are very low (2 mg per day) and widely covered by normal feeding. Pyridoxine deficiencies are exceptional (congenital metabolic abnormalities, drug or toxic-induced perturbations). First described in animal models, human cases of neuropathy had been encountered in the "megavitamin" syndrome. They are confirmed by rare case-reports of very high doses given in toxic indication. Sensory peripheral neuropathies can also occur with lower doses taken over a long period of time. PMID- 7878601 TI - [Colchicine poisoning apropos of a pediatric case]. AB - Colchicine has been widely used in the treatment of gout and familial mediterranean fever. Overdose is rare mostly in childhood. Colchicine overdose always causes gastrointestinal side effects, bone marrow depression and sometimes neuropathy. The mechanism of colchicine upon the microtubules, provides a better understanding of the pharmacology and also of the multiorgan involvement. We report the case of a ten year old child who ingested 0.6 mg/kg colchicine with a good outcome. PMID- 7878602 TI - [Erythrocyte superoxide dismutase (eSOD) determination in positive moments of psychosis]. AB - Dysregulation of free radical metabolism has been supposed to be involved in schizophrenia etiopathogeny. Recently, Wang et al. showed a red blood cell super oxide dismutase increase in positive schizophrenia (Crow's type I), but neither in negative schizophrenia (Crow's type II) nor in controls. The study included 28 in-patients suffering from acute positive psychosis who were compared with 15 controls. We confirmed the results of Wang. We found a significantly red blood cell Super oxide dismutase increase in positive psychosis, in comparison to negative psychosis and controls (p = 0.0001). This SOD increase was in relationship with the degree of clinical psychomotor excitement. After 21 days of neuroleptic treatment, SOD activity decreased and reached standard values. These results support the hypothesis of striking relationships between catecholaminergic hyper-metabolism and SOD increase, in positive psychosis. These could account for psychotic positive symptoms improvement with neuroleptic treatment, which blocks dopamine pathways. PMID- 7878604 TI - [Thrombosis and carbamazepine: hazard or causality?]. PMID- 7878603 TI - [Demonstration of the fibrillatory effect of class I anti-arrhythmia agents based on the time of fibrillation onset and electrical threshold in myocardial ischemia]. AB - In recent clinical studies, certain class I antiarrhythmic drugs (flecainide, lidocaine) appeared to be responsible for an increase in mortality, when used to treat ventricular arrhythmias occurring after or during infarction. Experimentally, in pigs whose rate of ventricular beats was kept constant by pacing, all the studied class I antiarrhythmic drugs, disopyramide, lidocaine and flecainide, proved to be to a variable degree capable of shortening time to onset of fibrillation (TOF) elicited by controlled myocardial ischemia. Fibrillation occurred at the end of the decline, under the influence of ischemia, of electrical fibrillation threshold (EFT) down to near 0 mA. The fall of EFT to this level was checked by ischemias of increasing duration to be hastened by the cited antiarrhythmic drugs. In other words, these drugs exert a profibrillatory effect in the ischemic heart. PMID- 7878605 TI - [Heparins and transaminases: an enigma without importance in 1994?]. PMID- 7878606 TI - [A new case of neurotoxicity of 5-fluorouracil by short perfusion at high-dose]. PMID- 7878607 TI - [Recurrent pericarditis induced by mesalazine (5-ASA)]. PMID- 7878608 TI - [Impotence and gynecomastia secondary to hyperprolactinemia induced by ranitidine]. PMID- 7878609 TI - [Fulminant hepatitis secondary to alprazolam]. PMID- 7878610 TI - [Transplacental transport and feto-placental metabolism of drugs: study methods, therapeutic contributions and implications]. AB - Pregnancy is a specific dynamic state and the potential usefulness of caring for a fetal and/or adjacent disorder by treating the mother is now well established. Pregnant women being excluded from the investigational field of clinical trials, only few studies exist concerning evaluation of the pregestational metabolism or transplacental transfer (TPT) of drugs. Questions are extensive and complex. Does TPT occur at a given gestational age (GA), in the context of a particular type of pathology, when a drug is administered by a certain dosage regimen? If this is the case, what is the rapidity of penetration of the products of conception by the drug (bearing in mind its physical-chemical characteristics)? Need harmful adverse effects on the child be feared? Is such penetration desirable, of no consequence or dangerous? Does the possibility exist of accumulation in the placenta, fetal tissue or amniotic fluid? Should such findings modify the therapeutic regimens of drugs given to expectant mothers? After dealing with the ethical and physiological context in which such research is undertaken, the authors review methods for the study of TPT developed both in vitro and in vivo. The current review covers the period between 1972 and 1993. Exchange mechanisms are complicated and models developed in vitro only partially reflect the actual equilibria which develop. These include: 1) the perfused cotyledon model, which while simple, elegant and inexpensive, offers only a localized and fixed view of pregnancy; 2) the necessary study, using microsomes, of placental metabolic capacity (enzyme cartography). In vivo study of TPT is based upon various multicompartmental pharmacokinetic models, some of which have been relatively validated in animals. The simplest indicator for the in vivo evaluation of TPT of a drug in the human species is determination of a feto-maternal blood concentrations ratio (usually performed at the time of separation). The usefulness and limitations of this parameter are controversial, and it would seem preferable to associate it with a kinetic profile of variations in blood concentrations established in the mother. Any extrapolation of a single result to fetal and adjacent tissues must be done with the greatest caution. Study of the TPT of therapeutically useful agents is essential to the understanding of their metabolism and is a prerequisite to the use of medications during pregnancy, bearing in mind that any such use must always be with the greatest care and with extremely well-founded indications. PMID- 7878611 TI - [Drug conjugation in the brain]. AB - Several drugs and environmental pollutants can cross the blood-brain barrier and reach the brain. This organ possesses an enzymatic equipment able to metabolize xenobiotics, therefore facilitating their elimination and maintaining brain homeostasis. This metabolism may result in the formation of toxic metabolites, which endanger neuronal integrity and may result in neurological disturbances. The main function of the conjugation enzymes present in the brain parenchyma and blood-brain or blood-cerebrospinal fluid interfaces is the detoxification of these reactive molecules, thus protecting the central nervous system. This review presents the main cerebral conjugating enzymes, and shows the interest for the design of new drugs of the knowledge of their activities. PMID- 7878612 TI - [A case of metabolic interaction: amitriptyline, fluoxetine, antitubercular agents]. AB - Polytherapy is often used in clinical practice. The drug associations may lead to pharmacokinetic and/or pharmacodynamic interactions, with clinical implications. The authors reported a quantified illustration of 2 types of interactions in a depressed patient: between antidepressants, amitriptyline and fluoxetine, between these antidepressants and antituberculosis. Firstly, when fluoxetine was added to amitriptyline, it was observed, as expected, an increase of the tricyclic and its metabolite plasma levels, despite a decrease of its dosage. Secondly, when antituberculosis were added to the 2 antidepressants, it was observed a decrease of the tricyclic drug plasma levels. These levels remained below the therapeutic window even when the tricyclic antidepressant dosage was increased. It seems that the fluoxetine interaction disappeared. The competition between the inhibitory effect of fluoxetine and the induction of rifampicin, on the metabolism of amitriptyline is discussed. PMID- 7878613 TI - [Chorea-athetosis syndrome under the effect of carbamazepine and viloxazine. Consequence of drug interaction?]. PMID- 7878614 TI - [Ventricular tachycardia after levomepromazine overdose]. PMID- 7878615 TI - [Non-thrombopenic purpura induced by amlodipine]. PMID- 7878616 TI - Fluconazole-induced agranulocytosis [. PMID- 7878617 TI - [Hypereosinophilia associated with heparin: a case with a challenge test]. PMID- 7878618 TI - [Erythromelalgia and low molecular weight heparin]. PMID- 7878619 TI - [Rectal stenosis associated with Veganine suppositories. A new case]. PMID- 7878620 TI - [Hyperthermia due to methotrexate in Still's disease]. PMID- 7878621 TI - [Hepatotoxicity caused by dextropropoxyphene. Two cases, one of them with recurrence]. PMID- 7878622 TI - Inherited diseases of platelet glycoproteins: considerations for rapid molecular characterization. AB - The characterization of inherited diseases of platelets has provided valuable information about platelet physiology and platelet protein function. Genetic studies on patients with Glanzmann thrombasthenia, the Bernard-Soulier syndrome, and platelet-type von Willebrand disease have been confined to abnormalities of the GPIIb-IIIa and GPIb-IX receptor complexes. The primary molecular technique used in these analyses has been the polymerase chain reaction (PCR). The amplified PCR products are either directly sequenced, or used to screen for abnormal regions of the genes which are then sequenced. This review examines the known mutations in GPIIb-IIIa and GPIb-IX, focusing on those genetic issues which should dictate decisions regarding the approach to identifying molecular defects. The techniques for characterizing mutant alleles in Glanzmann thrombasthenia and Bernard-Soulier syndrome are described and a general strategy is offered. Because mutations resulting in reduced levels of transcripts can be missed when screening RNA, an argument is made for using genomic DNA as the primary material for mutation detection. PMID- 7878623 TI - Serological and virological markers of human parvovirus B19 infection in sera of hemophiliacs. AB - It is known that parvovirus B19 (B19) is transmitted to hemophiliacs by clotting factors prepared from human plasma. However, it is not clear whether B19 is also transmitted by the more recently used inactivated clotting factor preparations. Therefore, we investigated 69 hemophiliacs, mostly children, receiving only virus inactivated clotting factors. 49 of them (71%) were B19 IgG-positive and 18 of the IgG-positive hemophiliacs (37%) were also B19 IgM-positive. In contrast, out of 73 age-matched controls only 10 (14%) were IgG-positive, two of them being also IgM-positive. In hemophiliacs treated before 1984 with non-inactivated clotting factors, seroprevalence was very similar: 94/136 (69%) presented B19 IgG antibodies as compared to their age-matched controls with 16/50 (32%). Out of the 94 IgG-positive patients 24 (26%) were IgM-positive, whereas IgM antibodies were never found in 16 sera of 16 IgG-positive controls. In 4 out of 24 IgM positive hemophiliacs, B19 DNA was detected in the sera by using the polymerase chain reaction. However, B19 DNA was also found in 3/69 anti-B19 IgM-negative, HIV infected hemophiliacs (all three patients in CDC stage IV). Since it seems unlikely that the results only represent passive acquisition of B19 DNA from blood products and induction of antibodies by immunization with inactivated antigen, the observations rather suggest that infection with B19 is transmitted by clotting factors, including those treated for virus inactivation. PMID- 7878624 TI - Patterns of immunogenicity of an inactivated hepatitis A vaccine in anti-HIV positive and negative hemophilic patients. AB - Hepatitis A vaccination has been recommended to patients with hemophilia since they are exposed to potentially infectious clotting factor concentrates. Aim of this study was to assess the immunogenicity of vaccination in hemophiliacs, infected or not with the human immunodeficiency virus (HIV). A formalin inactivated hepatitis A vaccine was injected subcutaneously to 113 susceptible adults and children and repeated after 1 and 6 months. 47 vaccinees were anti-HIV positive (28 asymptomatic, 15 with CD4 cell counts of less than 200/microliter and 4 with symptomatic disease). The first dose of vaccine induced seroconversion, with antibody titers of at least 20 mIU/ml, in 89% of the 66 anti HIV negative patients, 100% of them responding after the second injection. In anti-HIV positive hemophiliacs seroconversion rates and antibody titers were significantly lower than in non-infected patients. After 12 months, only 76% of anti-HIV positive vaccinees and 40% of those with signs of HIV disease progression maintained the antibody, whereas all anti-HIV negative patients had titers of 20 mIU/ml or more. Our results indicate that there is an association between defective response to hepatitis A vaccine and stage of progression of HIV disease. PMID- 7878626 TI - Homozygous type I protein C deficiency in two unrelated families exhibiting thrombophilia related to Ala136-->Pro or Arg286-->His mutations. AB - Separate single nucleotide mutations have been identified in two unrelated homozygous type I protein C deficient individuals suffering from thrombophilia. Each mutation, initially established by direct DNA sequencing of polymerase chain reaction amplification products, results in an amino acid substitution. The first mutation (PCClamart) results in an Ala136 to Pro substitution in the protein's second epidermal growth factor-like domain. The second mutation (PCMunchen) results in an Arg286 to His substitution in the serine protease domain. Comparison of the location of these two mutations and the relative conservation of the two regions in homologous vitamin K-dependent plasma proteins is consistent with the difference in severity of protein C deficiency and disease in the two individuals. Both mutations result in the abolition of a naturally occurring restriction endonuclease site, thereby allowing independent confirmation of the mutations and rapid and unambiguous genetic analysis of protein C deficiency in family members. In both families, the genetic analysis has proven useful in cases where an assignment of the protein C status based upon clinical laboratory measurements was either ambiguous or incorrect. PMID- 7878625 TI - Effects on thrombin generation of single injections of Hirulog in patients with calf vein thrombosis. AB - STUDY OBJECTIVE: To determine whether single injections of Hirulog, a direct thrombin inhibitor, can inhibit thrombin generation in patients with calf vein thrombosis and, if so, if the inhibition is sustained. DESIGN: Phase II open label cohort study. SETTING: Tertiary-care referral centres, university affiliated hospitals. PATIENTS: 10 patients with venographically-demonstrated calf vein thrombosis. INTERVENTION: Patients received a single injection of Hirulog, either 1.0 mg/kg subcutaneously or 0.6 mg/kg as a 15 min intravenous infusion. Prothrombin fragment (F1++2) levels, as an index of thrombin generation, were measured before as well as 6 h post- and 24 h post-Hirulog administration. Patients were followed with non-invasive tests to detect thrombus extension into the proximal veins. RESULTS: There was a significant reduction in the levels of F1+2 with both regimens, 6 h after Hirulog. The F1+2 levels 24 h post-Hirulog showed a significant increase relative to the 6 h post-Hirulog results. One patient developed thrombus extension into the popliteal vein and was treated with conventional anticoagulants. CONCLUSION: The single injections of Hirulog used in the study produced incomplete and temporary suppression of F1+2. Complete and permanent inhibition of thrombin generation with Hirulog in patients with calf vein thrombosis may require higher doses, multiple subcutaneous injections and/or prolonged intravenous infusion. PMID- 7878627 TI - Molecular basis of antithrombin type I deficiency: the first large in-frame deletion and two novel mutations in exon 6. AB - We report three novel mutations accounting for cases of inherited type I antithrombin (AT) deficiency. Using the polymerase chain reaction (PCR) and direct sequencing of the coding sequences of the AT gene, we found one mutation in exon 4 and two in exon 6. A deletion of 105 bp causing an in-frame deletion of 35 amino acids between Tyr 240 and Gly 276 was found in exon 4. In a second kindred, deletion of two adenines in codon 412-413 introduced a frameshift and a stop codon at position 431. The last mutation was an insertion of ACCG in codon 387, generating a frameshift with a stop codon located at the normal position. The finding of a sequence repeat of nine residues located at the 5' and 3' ends of the deleted fragment might explain the 105 bp deletion by slippage and mispairing at the replication fork during DNA synthesis. The second mutation is the fourth described within a region of six amino acids (between Phe 408 and Arg 413), which seems to be a cluster of mutations. In this case, the presence of a double repeat sequence--TTCCT and AACA--flanking this region could be particularly favorable for slipped mispairing. These results confirm that human gene mutations are not random events but are strongly influenced by DNA flanking sequences. PMID- 7878628 TI - Upper extremity impedance plethysmography in patients with venous access devices. AB - Central venous access devices (VADs) are often associated with thrombotic obstruction of the axillary-subclavian venous system. To explore the accuracy of impedance plethysmography (IPG) in identifying this complication we performed IPG on 35 adult cancer patients before their VADs were placed and approximately 6 weeks later. At the time of the second IPG the patients also underwent contrast venography of the axillary-subclavian system. The venograms revealed partial venous obstruction in 12 patients (34%) and complete obstruction in two (5.7%). Although the IPG results from venographically normal and abnormal patients overlapped extensively, mean measurements of venous outflow were significantly lower in the patient population with abnormal venograms (P = 0.052 for Vo; P = 0.0036 for Vo/Vc). In our hands, therefore, upper extremity IPG cannot be used to make clinical decisions about individual patients with VADs, but it can distinguish venographically normal and abnormal populations. PMID- 7878629 TI - Urokinase versus recombinant tissue plasminogen activator in thrombosed central venous catheters: a double-blinded, randomized trial. AB - Fifty dysfunctional central venous catheters proven radiographically to be occluded by thrombus were blindly randomized to be injected with either 2 mg recombinant tissue plasminogen activator (t-PA) or 10,000 units of urokinase (UK) and allowed to incubate for 2 h. A second dose was allowed if catheter function was not restored with the first injection. Repeat radiograph contrast injection was done when catheter function was restored or after 2 doses of study drug were administered, whichever occurred first. Thirteen of 22 catheters randomized to UK had full function restored compared to 25 of 28 randomized to t-PA (p = 0.013). Radiographic contrast injection showed 7 catheters randomized to UK had complete resolution of the thrombus compared to 17 randomized to t-PA (p = 0.042). Four catheters randomized to UK had complete resolution of the thrombus after a single dose compared to 13 randomized to t-PA (p = 0.036). A novel dose of 2 mg of t-PA restored catheter function more reliably and dissolved thrombi faster than twice the standard, FDA-approved dose of UK. PMID- 7878630 TI - Pulmonary embolism in patients with upper extremity DVT associated to venous central lines--a prospective study. AB - We performed a prospective study in 86 consecutive patients with central vein catheter-related deep venous thrombosis (DVT) of the upper extremity, to evaluate the prevalence of pulmonary embolism (PE), and to identify clinical variables that would increase the likelihood of developing PE in an individual patient. Since upper-extremity DVT was established, all patients received intravenous heparin therapy. Then, a ventilation-perfusion lung scan was obtained within 24 h of DVT diagnosis, whether respiratory symptoms were present or not. Six points of clinical information were recorded on entering in the study, and then compared with the scintigraphic findings: age, sex, the underlying disease, the catheter material, the character of the infusate, and the duration of cannulation. Thirteen patients were considered to have PE. Sixty-six patients were finally classified as having a normal lung scan, and 7 patients were excluded from the study (because of indeterminate lung scan 6; because of femoropopliteal thrombosis simultaneously present 1). Two out of the 13 patients with PE subsequently died because of recurrent, massive embolism, despite adequate heparin therapy. PE was more commonly present in patients with polyvinyle chloride or polyethylene catheters (10/38, 26%) as compared to patients with either polyurethane or siliconized catheters (3/41, 7%; p < 0.05, Chi-Square test; Odds Ratio = 4.52, 95% CI 1.01-23.07). We conclude that PE is not a rare event in these patients, and it may be life-threatening even despite adequate heparin therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878631 TI - Antithrombin III: associations with age, race, sex and cardiovascular disease risk factors. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. AB - Antithrombin III (AT III) is a major inhibitor of blood coagulation, and hereditary deficiency is associated with venous thrombotic disease. The Atherosclerosis Risk in Communities (ARIC) Study, a prospective study of 15,800 middle-aged men and women, measured AT III in its baseline examination. AT III levels were significantly higher in women than men, and in blacks than whites. AT III decreased with age in men but increased with age in women. In age- and race adjusted analyses, AT III was positively associated with smoking, HDL cholesterol, triglycerides (men only), and in women, with diabetes and lipoprotein(a). AT III was negatively associated with educational level, body mass index in men, and use of female hormones in women. Most of these associations were confirmed in multivariate analysis. These correlations between AT III and other risk factors must be considered when evaluating AT III as a risk factor for venous or arterial thrombosis. PMID- 7878632 TI - Both fish oil and olive oil lowered plasma fibrinogen in women with high baseline fibrinogen levels. AB - This double-blind, cross-over study with olive oil as placebo, examined the effect of a daily dosage of 6 g fish oil on cardiovascular risk markers of 20 healthy young volunteers (10 men, 10 women). Serum lipids and lipoproteins, and plasma coagulation and fibrinolytic enzymes, including fibrinogen concentrations and plasminogen activator inhibitor-1 (PAI-1) activity were measured at baseline and after 6-week supplementation of either fish or olive oil. The results showed that fish oil had an independent lowering effect on triglycerides and coagulation factors Vc and VIIc. Both fish and olive oil significantly raised PAI-1 levels and lowered plasma factor Xc and fibrinogen levels in the women, who had higher initial levels than the men. Mean fibrinogen levels of the women were lowered from 3.23 +/- 0.98 to 2.64 +/- 0.55 g/l and from 3.19 +/- 0.72 to 2.66 +/- 0.49 g/l by fish and olive oil respectively. This study raises the question whether a particular fatty acid or group of fatty acids, or another constituent of the oil such as vitamin E may be responsible for the fibrinogen lowering effect. PMID- 7878633 TI - Apolipoprotein(a), fibrinopeptide A and carotid atherosclerosis in middle-aged men. AB - The association between apolipoprotein(a) [apo(a)], fibrinogen, fibrinopeptide A (FPA) and carotid intima-media thickness (IMT) was analyzed in Eastern Finnish men aged 50 to 60 years. Apo(a) correlated directly with carotid bifurcation (r = 0.26, p = 0.001), but not with common carotid IMT. Men in the lowest quartile of apo(a) had thinner (p = 0.013) IMT in bifurcation [1.59 mm (95% CI 1.49; 1.68)] compared to the men in the highest [1.91 mm (95% CI 1.73; 2.09)] apo(a) quartile. The difference remained (p = 0.038) after adjusting for confounders. Plasma fibrinogen was not related to carotid IMT, whereas FPA correlated with common carotid (r = 0.21, p = 0.016) and carotid bifurcation (r = 0.21, p = 0.018) IMT. These associations abolished after adjusting for the confounders. The data suggest that apo(a) associate with carotid atherosclerosis independent of other risk factors for ischemic cardiovascular diseases. PMID- 7878634 TI - Calcium-dependent activation of protein C by thrombin/thrombomudulin: role of negatively charged amino acids within the activation peptide of protein C. AB - In the absence of its cofactor thrombomodulin (TM) thrombin is only a poor activator of the anticoagulant serine protease protein C (PC). The TM-dependence of PC-activation has been restricted to a series of molecular structures of the PC molecule including high-affinity calcium binding sites and single amino acid residues. However, thrombin induced activation of a PC derivative altered in all these critical positions is markedly enhanced by TM indicating that additional structures of the PC molecule are involved in determining the TM specificity. Based on the hypothesis that such an additional regulatory element should be located near the thrombin cleavage site and should include negatively charged amino acids to ascertain calcium binding, we studied whether Glu and Asp in positions P7 and P6 relative to the thrombin cleavage site together with Asp in P3 are involved in formation of such a regulatory element. Three PC derivatives containing the neutral counterpart of the negatively charged amino acids in positions P3; P3 and P6; and P3, P6, and P7, respectively, were generated using site-directed mutagenesis. Compared to rPC-wt the initial rates of PC activation of all three mutants were increased 4.0-fold for thrombin/TM and 4.0-, 5.3-fold for activation by thrombin alone. However, compared to the PC derivative neutralized exclusively in P3, additional changes in P6 and P7 showed no increase in the thrombin activation kinetics and calcium binding properties were identical in all of the three mutants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878635 TI - Thrombomodulin induction by all-trans retinoic acid is independent of HL-60 cells differentiation to neutrophilic cells. AB - The expression of thrombomodulin (TM), an antithrombotic factor, was investigated during neutrophilic differentiation of the HL-60 human myeloblastic cell line treated with all-trans retinoic acid (ATRA) or dimethyl sulfoxide (DMSO). Differentiation of the cells into neutrophilic cells progressed in a time- and dose-dependent fashion with ATRA or DMSO, as confirmed by the characteristic appearance of nitroblue tetrazolium (NBT) reduction and phagocytic activities, without induction of nonspecific esterase activity. TM antigen and cofactor activity for thrombin-dependent protein C activation were not detected in untreated HL-60 cells and the cells cultured with DMSO, but were expressed in a time-dependent manner in the cells cultured with ATRA. The level of TM expression in the HL-60 cells was not dose-dependent on ATRA concentrations, but maximum TM expression was obtained at 10(-7) M ATRA. TM expression levels decreased in cells cultured with greater than 10(-6) M ATRA, although the extent of cell differentiation into neutrophilic cells progressed at the higher ATRA concentrations. Since the TM antigen levels in the ATRA-treated cells also paralleled the TM mRNA levels, the data suggests that TM induction in the HL-60 cells cultured with ATRA reflected the levels of TM biosynthesis and was independent of HL-60 differentiation into neutrophilic cells. It was postulated that the appearance of TM with cofactor activity in neutrophilic cells differentiated from leukemic cells may contribute to prevention of vascular thrombosis in differentiation therapy of patients with acute promyelocytic leukemia by ATRA. PMID- 7878636 TI - The interaction of beta 2 glycoprotein-I and heparin and its effect on beta 2 glycoprotein-I antiphospholipid antibody cofactor function in plasma. AB - beta 2 glycoprotein-I (beta 2GPI), a cofactor for antiphospholipid antibody (aPA) binding, binds to many anionic macromolecules including heparin. The nature of this interaction with heparin is not well understood and its effect on the purported biological functions of beta 2GPI is unknown. We have examined the interactions of dermatan sulphate (DS) and different pharmaceutical preparations of heparin with beta 2GPI by crossed immunoelectrophoresis (CIE) and investigated the effect of these agents on plasma levels of beta 2GPI antigen (beta 2GPI:Ag) by a standardised enzyme linked immunosorbent assay (ELISA). beta 2GPI aPA cofactor activity (beta 2GPI:Cof) was also measured using a modified solid phase anti-phosphatidylserine (aPS) ELISA. CIE results confirmed a heparin-beta 2GPI interaction with unfractionated (UF) heparin. beta 2GPI:Ag levels were unaffected by any of the preparations investigated. There were no significant differences in beta 2GPI:Cof activities of the samples containing LMW heparins or DS but levels of beta 2GPI:Cof were increased in samples containing UF sodium and calcium heparin preparations (0.5 IU/ml Monoparin, p < 0.05, and 10 IU/ml Liquemin and Calciparine, p < 0.05). PMID- 7878637 TI - A chromogenic test to determine the procoagulant phospholipids in platelet-rich plasma and whole blood. AB - We have developed a chromogenic assay to measure the phospholipid-related procoagulant activity (PPA) in whole blood, or platelet-rich plasma. The test is based upon thrombin formation from prothrombin by prothrombinase and is designed in such a way that procoagulant lipids are rate limiting for the prothrombinase activity. In the chromogenic test PPA concentrations equivalent to 0-10 nM phospholipid vesicles containing 75% phosphatidyl choline (PC) and 25% phosphatidyl serine (PS) can be measured. The thrombin, which develops during the test, is measured with a chromogenic substrate. By the action of thrombin on this chromogenic substrate p-nitroaniline is liberated, which causes an increase in absorbance. Thrombin formed in the assay mixture activates the present platelets. This causes a linear increase of the velocity of thrombin generation during the test, i.e. a parabolic increase of product formation. For that reason the thrombin generation in time is characterized by two parameters, the basal PPA (PPA-B) of the original mixture and the increase in PPA due to platelet activation (PPA-A). To determine these figures the absorbency-data were fitted to parabolas. In most cases the contribution of PPA-A to the total amount of formed thrombin becomes considerable already after 30 s. Preliminary tests show that PPA B activity in whole blood or platelet-rich plasma of patients with a thrombotic disorder is significantly higher than the activity of a control group of the same age. PMID- 7878638 TI - Release of tissue-type plasminogen activator in response to muscarinic receptor stimulation in human forearm. AB - We have recently shown that mental stress increases local net release of tissue type plasminogen activator (t-PA) across the forearm vascular bed. However, the mechanisms responsible for the t-PA release in man during stress are undefined. To study the effects of endothelial cell receptor stimulation and fluid shear stress we used the perfused forearm model to characterize the in vivo tissue plasminogen activator (t-PA) response in man to methacholine (Mch) and sodium nitroprusside (SNP), at doses calculated to cause similar degrees of vasodilation. The study was performed in 7 healthy young men (age 22-24 yrs) without hypertension, diabetes mellitus, or hypercholesterolemia. Each subject received double-blind step-wise i. a. infusions of Mch (0.1-0.8-4.0 micrograms/min) and SNP (0.5-2.5-10 micrograms/min) in randomized order. Each dose step was infused for 5 min. Forearm blood flow was assessed by plethysmography. Net release/uptake was expressed as the product of arterio venous concentration gradient and forearm plasma flow. At pre-infusion baseline, there was a significant net release of t-PA antigen of approximately 0.9 ng x min 1 x 100 ml-1 and t-PA activity of 3.5 fmol x min-1 x 100 ml-1 across the forearm. I.a. infusion of Mch and SNP increased forearm blood flow from 1.9 to 14.9 and from 1.8 to 12.1 ml x min-1 x 100 ml-1, respectively (Mch vs SBP N.S.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878639 TI - Characterization of a novel streptokinase produced by Streptococcus equisimilis of non-human origin. AB - Streptokinases are proteins with plasminogen activator activity produced by certain hemolytic streptococci. We previously identified equine streptococcal isolates which produced streptokinases (ESKs) that bound both human and equine plasminogen but only readily activated equine plasminogen (14). This property was exploited to purify a representative ESK produced by Streptococcus equisimilis strain 87-542-W. Affinity chromatography with human plasminogen resulted in the isolation of a M(r) approximately 49,000 molecule with two isoforms. This ESK was subsequently compared to well characterized streptokinases (HSKs) that efficiently activate human plasminogen. Differences in streptokinases were identified in the highly conserved amino-terminal amino acid sequence, peptide maps, and antigenic properties, and these differences were supported by DNA hybridization studies. These results indicate that the family of proteins identified as streptokinases has much greater diversity than previously appreciated. PMID- 7878640 TI - The platelet adhesion capacity to subendothelial matrix and collagen in a flow model during storage of platelet concentrates for 7 days. AB - The influence of storage of platelet concentrates (PC) on the adhesion capacity of platelets was studied. Twenty-four PC, 12 prepared by the buffy coat (BC) method and 12 by the platelet-rich plasma (PRP) method, were stored for 7 days at room temperature. On days 1, 3 and 7 of storage, the platelet adhesion capacity to subendothelial matrix (SEM) and collagen was studied in a rectangular perfusion system under flow conditions in conjunction with the platelet aggregation capacity after stimulation and the adenine nucleotide content. The platelet adhesion capacity to collagen was constant until day 3 of storage and decreased to about 80% of the starting value on day 7 of storage. The adhesion capacity to SEM, however, had already decreased on day 3 to about 75% of the value of day 1 and was even more decreased on day 7 to about 45% of the starting value. On day 1, platelets prepared by the BC method displayed a higher adhesion capacity to collagen and a higher aggregation capacity after stimulation by collagen alone or in combination with ADP, compared to platelets prepared by the PRP method. No other significant differences in adhesion or aggregation capacity were observed between the PC prepared by the two different methods. Both platelet adhesion and aggregation response decreased during storage, as did the total adenine nucleotide content. This study shows that platelet function, as measured by the aggregation and adhesion capacity, of platelets prepared by the PRP method is more severely impaired during the first 3 days of storage as compared to the function of platelets prepared by the BC method. PMID- 7878641 TI - In vivo antithrombotic effect of triflavin, an Arg-Gly-Asp containing peptide on platelet plug formation in mesenteric microvessels of mice. AB - Triflavin, an Arg-Gly-Asp-containing snake venom peptide, inhibits platelet aggregation through the blockade of fibrinogen binding to the activated platelets. In this study, platelet thrombus formation was induced by irradiation of the mesenteric venules with filtered light in mice pretreated intravenously with fluorescein sodium. Electron microscopy reveals moderately damaged endothelial cells, as well as aggregates consisting almost exclusively of platelets with pseudopod formation, and degranulated appearance. Triflavin (10-20 micrograms/g) significantly prolonged the lag period of inducing platelet plug formation in mesenteric venules when it was intravenously infused. Triflavin (20 micrograms/g) prolonged the occlusion time about 2-fold (from control 112 +/- 23 to 240 +/- 47 s). Furthermore, PGE1 briefly prolonged the occlusion time about 1.5-fold (from 105 +/- 21 to 168 +/- 20 s) when it was given by continuous infusion (40 micrograms/kg/min). On the other hand, triflavin was also effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice when administered intravenously at dose of 2-4 micrograms/g. Heparin (1.5 U/g) and indomethacin (200 micrograms/g) had no significant effect in prolonging the occlusion time or in reducing ADP-induced pulmonary embolism in mice. Therefore, triflavin is an effective antithrombotic agent in preventing the thromboembolism in these two in vivo models. PMID- 7878642 TI - Effect of acetylsalicylic acid on inhibition of ex vivo platelet aggregation and secretion by SKF 107260, a novel GPIIb/IIIa receptor antagonist. AB - SKF 107260 is a potent pentapeptide antagonist of the platelet membrane glycoprotein receptor GP IIb/IIIa. The in vitro platelet inhibitory effects of SKF 107260, acetylsalicylic acid (ASA), and their combination, on collagen induced platelet aggregation and secretion (ATP release) were assessed in human whole blood. Additionally, the concentration-response relationships for these inhibitors were compared for males and females in order to explore gender differences in platelet responsiveness. SKF 107260 caused a concentration dependent inhibition of platelet aggregation which was significant at concentrations > or = 30 nM. ASA also caused a concentration-dependent inhibition of platelet aggregation which was significant at concentrations > or = 1 mg/dl. The addition of ASA 1 mg/dl to increasing concentrations of SKF 107260 resulted in a more pronounced inhibition of platelet aggregation than when either agent was used alone. These data suggest a pharmacologic interaction, especially at SKF 107260 concentrations < or = 30 nM. Since ATP release was significantly inhibited at concentrations > or = 1 nM, platelet secretion appears to be more sensitive than aggregation to inhibition by SKF 107260. These data suggest that platelet secretion in response to collagen is dependent on the aggregation response mediated by GP IIb/IIIa. In conclusion, SKF 107260 is a potent inhibitor of both whole blood platelet aggregation and secretion and these anti-aggregatory effects may be augmented by concomitant ASA administration. PMID- 7878643 TI - Species variability in platelet and other cellular responsiveness to thrombin receptor-derived peptides. AB - The aggregation of platelets from a variety of animal species in response to thrombin receptor-derived activating peptides was evaluated. A series of 14 (SFLLRNPNDKYEPF), 7-(SFLLRNP-NH2), 6-(SFLLRN-HN2) or 5-(SFLLR-NH2) residue peptides, the structures of which were based on the deduced amino acid sequence of the human thrombin receptor, promoted full aggregation of platelets in plasma from humans, African Green and Rhesus monkeys, baboons and guinea pigs at 4-50 microM depending on the peptide used. Platelets in plasma from rabbit, dog, pig, and hamster underwent a shape change but failed to aggregate in response to these peptides over 3 log units of peptide up to 800 microM, despite being fully responsive to human thrombin. However, because the receptor peptides induced shape change in the platelets from these non-aggregating species, they apparently can activate some of the intracellular signaling system(s) usually initiated by thrombin in these platelets. In contrast, platelets from rats did not undergo shape change or aggregate in response to the peptides. A 7-residue receptor derived peptide based on the deduced amino acid sequence of the clone of the hamster thrombin receptor (SFFLRNP-N2) was nearly as efficacious as the corresponding human receptor-derived 7-residue peptide to promote aggregation of human platelets. However, the hamster peptide could not promote aggregation of hamster platelets in plasma at up to 800 microM peptide, while a shape change response was elicited. Platelets from rats, rabbits and pigs also did not aggregate in response to this peptide derived from the hamster thrombin receptor, but all species except the rat underwent a shape change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878644 TI - The tyrosine kinase inhibitors, genistein and methyl 2,5-dihydroxycinnamate, inhibit the release of (3H)arachidonate from human platelets stimulated by thrombin or collagen. AB - We have investigated the effects of the tyrosine kinase inhibitors, genistein and methyl 2,5-dihydroxycinnamate, on [3H]arachidonic acid release from human platelets. Both tyrosine kinase inhibitors blocked, in a dose-dependent manner, the release of arachidonic acid stimulated by thrombin or suspensions of collagen fibres. Blockade by the tyrosine kinase inhibitors occurred early in the arachidonate release time course. Both genistein and methyl 2,5 dihydroxycinnamate also inhibited tyrosine phosphorylation in platelets. The inhibitors were specific in that they did not affect protein kinase C activity, ATP levels or mobilization of Ca2+ from internal stores. These findings suggest a role for tyrosine kinase activity in the regulation of phospholipase A2 in platelets stimulated by the physiological ligands, thrombin and collagen. PMID- 7878645 TI - Treatment of acquired von Willebrand syndrome with intravenous immunoglobulin. PMID- 7878646 TI - Crossreactivity studies between sera of patients with heparin associated thrombocytopenia and a new low molecular weight heparin, reviparin. PMID- 7878647 TI - Influence of lupus anticoagulant on a commercially available kit for APC resistance. PMID- 7878648 TI - Plasma resistance to activated protein C in venous and arterial thrombosis. PMID- 7878649 TI - Another protein S functional assay is sensitive to resistance to activated protein C. PMID- 7878650 TI - Viral safety and clotting factor concentrates. PMID- 7878651 TI - Measurement of activated factor VII using soluble mutant tissue factor--proposal for standardization. PMID- 7878652 TI - Why is plasma fibrinogen a cardiovascular risk factor? PMID- 7878653 TI - Selection of unrelated bone marrow donors by PCR-SSP typing and subsequent nonradioactive sequence-based typing for HLA DRB1/3/4/5, DQB1, and DPB1 alleles. AB - HLA incompatibility between bone marrow recipients and unrelated donors is one of the main obstacles in bone marrow transplantation. HLA class I and generic class II DR and DQ typing is generally performed by serology. Precise subtyping of HLA class II genes, however, can only be achieved by molecular genetic methods. Here, the final selection of serologically pretyped unrelated bone marrow donors by confirmatory PCR-SSP (PCR-sequence-specific primers) typing and subsequent nucleic acid sequence analysis of the second exon of DRB1, DRB3, DRB4, DRB5, DQB1, and DPB1 alleles is presented. Serologically identical potential marrow donors and their corresponding recipients were analyzed for HLA-DRB identity by PCR-SSP analysis. After solid-phase single-strand separation, direct sequencing of the allele- or group-specific DRB amplified products was performed by applying fluorophorlabelled sequencing primers. Electrophoretically separated sequencing products were detected by means of an automated DNA sequencer. Group-specific amplification and sequencing of DQB1 alleles was carried out for all potential bone marrow donors and recipients, while only the final donor-recipient pair was analyzed for DPB1 alleles. Thus, the presented amplification strategy in combination with direct sequencing of PCR products allows matching of bone marrow transplant pairs with the highest degree of reliability for the assessment of HLA class II identity. PMID- 7878654 TI - Changes in expression of the cell adhesion molecule PECAM-1 (CD31) during differentiation of human leukemic cell lines. AB - PECAM-1, a member of the immunoglobulin gene superfamily, is widely distributed on cells of the vascular system, and mediates cellular interactions through both homotypic and heterotypic adhesive mechanisms. Previous studies have demonstrated that PECAM-1 is initially expressed at high levels on CD34+ multipotential progenitors in the bone marrow, but is subsequently downregulated in more committed precursors of all lineages. Interestingly, although PECAM-1 expression is high on circulating monocytes and neutrophils, little is known about the upregulation of PECAM-1 expression during terminal myelomonocytic differentiation. We have further characterized this process by examining PECAM-1 expression during chemically-induced differentiation of the U937, HL-60 and HEL cell lines. Quantitative Western blot analysis of cellular lysates indicated that PECAM-1 expression could be upregulated in U937 and HL-60 cells by phorbol esters or dimethyl sulfoxide. Northern blot analysis showed that PECAM-1 mRNA levels appeared to increase in parallel with that of PECAM-1 protein. We also observed a marked difference in the apparent molecular mass of PECAM-1 that was lineage specific, both in differentiated leukemic cell lines and in their corresponding leukocyte population. Immunofluorescence localization indicated that the cellular distribution of PECAM-1 in U937 and HL-60 cells was similar to that of their normal circulating counterparts, and that the pattern of distribution again displayed lineage fidelity. The ability to induce the expression of PECAM-1 molecules having different glycosylation and surface expression patterns may prove useful for further elucidation of the role of PECAM-1 in hematopoiesis, as well as studies of the cell lineage-specific modulation of PECAM-1 function. PMID- 7878655 TI - Striking conservation of three extended HLA-DR13 haplotypes in the Japanese population. AB - HLA class II DNA typing was conducted for 1335 unrelated Japanese individuals. The study on the linkage disequilibrium revealed a striking conservation of HLA DR13 haplotypes. Among these Japanese, 155 were typed for HLA-DR13 serologically, and they were correspondent to three DRB1 alleles, DRB1*1301, 1302 and 1307 defined by using the polymerase-chain reaction and sequence-specific oligonucleotide probe (PCR-SSOP) method. The two alleles, DRB1*1301 and 1307 were exclusively associated with each specific DRB3-DQA1-DQB1 combination which was DRB1*1301-DRB3*0101-DQA1*0103-DQB1*0603, and DRB1*1307-DRB3*0202-DQA1*0501 DQB1*0301, respectively. DRB1*1302, the most common DR13 allele in Japanese, had two significant associations with DRB3*0301-DQA1*0102-DQB1*0604 (DRB1*1302A) and with DRB3*0301-DQA1*0102-DQB1*0605 (DRB1*1302B). In this study, no other DR13 class II combinations were found. Only the DRB1*1302A halotype was associated with the DPB1*0401 allele while the DRB1*1302B haplotype was not. The complete conservation of these DR13 class II haplotypes was found to extend toward the HLA class I region. They were HLA A3-B44-DRB1*1301, A33-B44-DRB1*1302A and A33-B17 DRB1*1302B. Japanese could be characterized with these three extended haplotypes which were remarkably different from those in Caucasian, Black and Asian other than Korean populations. PMID- 7878656 TI - A new simplified method of gene typing. AB - SSP-PCR (sequence-specific primer) DNA typing was performed in Terasaki trays using 1.5 microliters of DNA, and the ethidium-stained PCR product was measured by direct fluorometric reading. Elimination of the gel electrophoresis step greatly simplified the SSP method. 17 serological DR specificities were discriminated for 239 DNA samples utilizing the new method, standard SSP, sequence-specific oligonucleotide probe (SSOP), and restriction fragment length polymorphism (PCR-RFLP). Results showed 98% concordance between the SSP-PCR assay and conventional methods. DRB1 alleles were determined by PCR-RFLP in 59 samples, by SSP in 110 samples, and by consensus (all methods) in the remaining samples. PMID- 7878657 TI - Characterization of natural peptide ligands for HLA-B*4402 and -B*4403: implications for peptide involvement in allorecognition of a single amino acid change in the HLA-B44 heavy chain. AB - This study describes the characterization of endogenous peptides associated with the two major subtypes of HLA-B44. The two subtypes differ for a single amino acid substitution from Asp (HLA-B*4402) to Leu (HLA-B*4403) in position 156 of the alpha 2 domain, causing strong alloreactivity in vivo. In order to study the involvement of peptides in this phenomenon, the peptide motifs of the two subtypes were determined from natural peptide pools using Edman degradation. The motif was found to be essentially identical for HLA-B*4402 and -B*4403, with a strong predominance for Glu at position 2, Tyr or Phe at positions 9 and 10 and hydrophobic residues, especially Met, at position 3. Two individual naturally processed ligands of HLA-B*4403 were sequenced and shown to be derived from intracellularly expressed proteins found in protein sequence databases. The sequence of these natural peptide ligands conform well to the determined motif. These data will allow the prediction of HLA-B44 restricted peptide epitopes from viral and tumor antigens of known amino acid sequences. Moreover, they indicate that the peptide repertoire presented by HLA-B*4402 and -B*4403 is very similar, suggesting that the strong alloresponse between these two subtypes is not due to presentation of a different set of self peptides. PMID- 7878658 TI - Structure of a novel subtype of B7 (B*0705) isolated from a Chinese individual. PMID- 7878659 TI - Distribution of alleles at D6S105 and D6S265 with possible HLA haplotype associations. PMID- 7878660 TI - DRB1*1504 (DR2Dai): a new DR2 allele identified in the Dai minority population of southwest China. PMID- 7878661 TI - Different DRB1*04 alleles predominate in the Finnish random population and in HLA B27-positive subpopulations. PMID- 7878662 TI - Cell surface antigen stability of cultured human umbilical vein vascular endothelial (VEC) cells. PMID- 7878663 TI - HLA DPA1-DPB1 linkage disequilibrium in the British caucasoid population. PMID- 7878664 TI - Evidence for lipoxygenase-catalyzed bioactivation of phenytoin to a teratogenic reactive intermediate: in vitro studies using linoleic acid-dependent soybean lipoxygenase, and in vivo studies using pregnant CD-1 mice. AB - Teratogenicity of the anticonvulsant drug phenytoin and structurally related compounds has been postulated to result in part from its cooxidative bioactivation to an embryotoxic reactive intermediate by the hydroperoxidase component of arachidonic acid-dependent prostaglandin H synthase (PHS). However, lipoxygenases (LPOs) could constitute a competing, arachidonate-dependent bioactivating system. The teratologic importance of LPO alone and together with PHS was evaluated in vitro and in vivo. To evaluate directly the potential role of LPO in phenytoin bioactivation, in vitro incubation conditions measuring the linoleic acid-dependent, soybean LPO-catalyzed covalent binding of phenytoin to protein, believed to constitute teratologic initiation, were optimized for substrate concentration, enzyme activity, incubation time, inhibitor vehicle, and inhibitor concentration. Under optimal conditions, 4.24 nM [3H]phenytoin, 100,000 units of soybean LPO (Type 1B, Sigma Chemical Co.), and 5 mg bovine serum albumin, with or without 5 mM linoleic acid, were adjusted with 100 mM Tris-HCl buffer (pH 9) to a 1-ml final volume and incubated at 37 degrees C for 60 min. Addition of linoleic acid substrate to the incubation medium enhanced the covalent binding of phenytoin by over threefold (p < 0.05). Linoleic acid dependent covalent binding of phenytoin was inhibited in a concentration dependent fashion by the selective and nonselective LPO/PHS inhibitors indomethacin, nordihydroguaiaretic acid, quercetin, BW755C, and 5,8,11,14 eicosatetraynoic acid (ETYA) and by the hydroperoxidase inhibitor methimazole (p < 0.05). In vivo, on Gestational Days 12 and 13, pregnant CD-1 mice were treated with the irreversible dual PHS/LPO inhibitor ETYA (0, 0.5, 5, 50, 100, and 125 mg/kg ip) or its vehicle, 2 hr before a teratogenic dose of phenytoin (65 mg/kg ip). Dams were killed on Day 19 and the fetuses were delivered by Caesarian section. ETYA pretreatment produced a dose-related decrease in phenytoin teratogenicity, with maximal reductions by 50 mg/kg of ETYA in the incidence of phenytoin-induced fetal cleft palates (1.8 +/- 1.8% vs 26.8 +/- 3%) (% +/- SE; p < 0.00001) and resorptions (22.5 +/- 5% vs 60 +/- 2%) (p < 0.05). Higher ETYA doses were embryotoxic. The reduction in phenytoin teratogenicity by the dual PHS/LPO inhibitor ETYA was considerably greater than that previously reported for acetylsalicylic acid, which inhibits only PHS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878665 TI - Exposure to TCDD during development permanently alters reproductive function in male Long Evans rats and hamsters: reduced ejaculated and epididymal sperm numbers and sex accessory gland weights in offspring with normal androgenic status. AB - Prenatal administration of relatively low doses of TCDD alters reproductive development and fertility of the progeny. Fertility was reduced in the progeny of Wistar rats exposed to 0.5 micrograms TCDD/kg/day from Gestational Day (GD) 6 to GD 15. In a three-generation reproduction study, TCDD reduced fertility of Sprague-Dawley rats in the F1 and F2 but not the F0 (no developmental exposure) generation at 0.01 microgram/kg/day in the diet. Furthermore, administration of TCDD on GD 15 (at 0.064 to 1 microgram/kg) both demasculinized and feminized morphology and behavior of Holtzman male rat offspring. Our objectives were to expand the observations of Mably et al. (1992, Toxicol, Appl. Pharmacol. 114, 97 107, 108-117, 118-126) on the effects of gestational administration of a single dose of TCDD to another strain of rat and another species, the hamster. In the first study, Long Evans (LE) hooded rats were dosed by gavage with 1 microgram TCDD/kg on GD 8 (during the period of major organogenesis) or GD 15 (the gestational day used by Mably et al.). In the second study, pregnant Syrian hamsters, a species relatively insensitive to the lethal effects of TCDD, were dosed on GD 11, equivalent to GD 15 in the rat, with TCDD at 2 micrograms/kg. When LE rats were dosed on GD 15, or when hamsters were dosed on GD 11, puberty (preputial separation) was delayed by about 3 days, ejaculated sperm counts were reduced by at least 58%, and epididymal sperm storage was reduced by 38%. Testicular sperm production was less affected. The sex accessory glands were also reduced in size in LE rat offspring treated on GD 15 despite the fact that serum testosterone (T), T production by the testis in vitro, and androgen receptor (AR) levels were not reduced. Some reproductive measures, such as anogenital distance and male sex behavior, were altered by TCDD treatment in rat but not hamster offspring. Since T and AR levels appeared normal in the sex accessory glands and the epididymis following perinatal TCDD exposure, the alterations in these tissues are not likely to have resulted from an alteration of the androgenic status of the male offspring. PMID- 7878667 TI - m-xylene toxicokinetics in phenobarbital-treated rats: comparison among inhalation exposure, oral administration, and intraperitoneal administration. AB - Rats, pretreated with phenobarbital (PB) for 3 days (80 mg/kg/day), were challenged with m-xylene orally or intraperitoneally at a small (0.01 ml/kg or 0.081 mmol/kg) or a large (0.10 ml/kg or 0.814 mmol/kg) dose, or by 6-hr inhalation exposure at a low (40 ppm) or a high (400 ppm) concentration. The concentrations of m-xylene and its major metabolite, m-methyl hippuric acid (m MHA), were measured over time in the blood and urine, respectively. PB treatment, which increased the hepatic metabolism of m-xylene in vitro about sixfold, had a significant effect on the metabolism of inhaled m-xylene (decreased blood m xylene concentration together with increased urinary excretion of m-MHA) only at a high exposure concentration (400 ppm). On the other hand, the enzyme induction had a significant effect on the metabolism of orally administered m-xylene either at a small (0.081 mmol/kg) or a large (0.814 mmol/kg) dose, due to the first-pass metabolism that plays a great role in this route. When m-xylene was administered intraperitoneally, the effect of enzyme induction was shown only at the large dose, a finding which suggests that intraperitoneal administration is more similar to inhalation exposure than oral administration. However, in agreement with oral administration but in contrast to inhalation exposure, PB treatment increased the urinary excretion of m-MHA only shortly after intraperitoneal administration of m-xylene, with no significant increase occurring in the total amount of m-MHA excreted in the urine, despite the great difference in the blood m-xylene concentration between PB-treated and control rats. PMID- 7878666 TI - In vitro acrylamide exposure alters growth cone morphology. AB - Acrylamide intoxication leads to degeneration of the longest axons of the central and peripheral nervous systems in humans and laboratory animals. Axonal derangements resulting from in vivo acrylamide exposure are first noted within synapses of the longest axons before involving more proximally located axonal segments or shorter axons, thus illustrating the specificity of acrylamide for the terminal axonal regions. As a possible model system for investigating the mechanism of toxicity of acrylamide on the distal axon, we exposed neurite extending chick dorsal root ganglion (DRG) cells to acrylamide in vitro and then examined growth cones for alterations in morphology and function. Exposing DRG explants to media containing from 0.125 to 1.0 mM acrylamide for 16 hr leads to specific and dose-responsive alterations of growth cone morphology including: a nearly total loss of filopodial elements, the preservation of highly active but two-dimensional lamellar structures, an inappropriate extension of the axonal cytoskeleton into the forward region of most growth cones, and a frequent breakdown of the central and peripheral growth cone domains. The sulfhydryl alkylating agents ethacrynic acid, iodoacetamide, and iodoacetic acid were tested and none produced acrylamide-like morphological alterations at any dose. DRG cultures were also exposed to the neurotoxic acrylamide analogs glycidamide, N hydroxy-methacrylamide (HM-ACR), and methacrylamide (M-ACR). At concentrations of 0.25 to 1.0 mM, glycidamide exposure resulted in acrylamide-like growth cone alterations. HM-ACR exposure also resulted in growth cones that were acrylamide like but only at concentrations > 1.5 mM. M-ACR did not produce acrylamide-like growth cones at doses of up to 16.6 mM. Thus, in vitro exposure of DRG explants to acrylamide and two neurotoxic acrylamide analogs leads to reproducible and specific morphological alterations that are dose-dependent and separable from the effects of sulfhydryl alkylation. PMID- 7878668 TI - Allometry in the uptake of hydrophobic chemicals determined in vivo and in isolated perfused gills. AB - Uptake rate constants of different classes of hydrophobic organic chemicals have been determined in isolated perfused gills of rainbow trout (Oncorhynchus mykiss) as an alternative for studies in vivo. The uptake rate constants have been compared to those determined in guppy, Poecilia reticulata, in vivo. The organic chemicals which have been used are anthracene, hexabromobenzene, octachloronaphthalene, octachlorodibenzo-p-dioxin, phenol, polychlorinated anisoles, polychlorinated benzenes, polychlorinated biphenyls, and tetrachloroveratrole. Uptake rate constants in guppy are higher than those in rainbow trout gills, and show relatively high variation in both gills and guppy. When uptake rate constants in each study are normalized for that of pentachlorobenzene (pCBz), variation is significantly reduced both in perfused gills and in guppy. All allometric relationship is derived between weight and uptake rate constant. Uptake rate constants determined in one fish can thus be used for prediction of those in other fishes. When a reference chemical, such as pCBz, is included, the gill perfusion experiments can be highly suitable to determine uptake rate constants of organic chemicals, which can be extrapolated to fish of different sizes. PMID- 7878669 TI - Aroclor 1242 stimulates the production of inositol phosphates in polymorphonuclear neutrophils. AB - Exposure in vitro to the mixture of polychlorinated biphenyls (PCBs), Aroclor 1242, stimulates superoxide anion (O2-) production and degranulation in rat polymorphonuclear neutrophils (PMNs). The mechanism by which PCBs activate PMNs is unknown. Phospholipase C-dependent hydrolysis of membrane phosphoinositides is an important early event in PMN activation in response to several agonists including N-formyl-methionyl-leucyl phenylalanine (fMLP); therefore, the present study was undertaken to determine whether Aroclor 1242 stimulates the production of inositol phosphates in isolated rat PMNs. PMNs elicited with glycogen from rat peritoneum were labeled with myo-[2-3H]inositol, and the effect of fMLP and Aroclor 1242 on accumulation of [3H]inositol phosphates was determined. Both fMLP (in the presence of cytochalasin B) and Aroclor 1242 induced rapid breakdown of inositol-containing phospholipids. Peak accumulation of [3H]inositol phosphates occurred within 5 sec in response to Aroclor 1242 and within 15-30 sec in response to fMLP. In cytochalasin B-treated PMNs, significant O2- generation occurred within 5 min of exposure to fMLP or Aroclor 1242. 2,2',4,4' Tetrachlorobiphenyl (TCB), but not 3,3',4,4'-TCB, stimulates O2- production and degranulation in isolated rat PMNs. To determine whether inositol phosphate accumulation parallels PMN activation, [3H]inositol monophosphate (IP) production was measured in response to Aroclor 1242, 2,2'4,4'-TCB, and 3,3'4,4'-TCB in LiCl treated cells. Both Aroclor 1242 and 2,2',4,4'-TCB, but not 3,3',4,4'-TCB, caused significant accumulation of [3H]IP. Previous reports indicate that cytochalasin B enhances PMN activation in response to fMLP by increasing the production of inositol phosphates. Pretreatment of PMNs with cytochalasin B significantly enhanced O2- production in cells exposed to Aroclor 1242 but did not alter [H]IP accumulation. These data suggest that treatment of rat PMNs with Aroclor 1242 stimulates PI turnover and are consistent with the hypothesis that hydrolysis of membrane phospholipids is important in PMN activation by PCBs. The enhancing effect of cytochalasin B on PCB-induced O2- production, however, likely involves other mechanisms. PMID- 7878670 TI - Constitutive expression of metallothionein genes in mouse brain. AB - Metallothioneins (MTs) are ubiquitous low-molecular-weight proteins that are induced by a variety of inducers, including metals, lipopolysaccharides (LPS), cytokines, oxidative stress, etc., and are thought to play a protective role against various toxic insults. The constitutive level of metallothionein is an important determinant of a tissue's susceptibility to toxic insults. In the present study, we report the constitutive expression of MT mRNAs in adult mouse brain. Analysis of total RNA from whole brain by Northern blot and solution hybridization showed that mRNAs for all three MT isoforms (I, II, III) were constitutively expressed in mouse brain, and there was no remarkable difference in their expression. However, in quantitative terms the order of expression was MT-I > MT-III > MT-II. The expression of MT-III and MT-II was about 70 and 50% of that of MT-I, respectively. Examination of their constitutive expression in different brain regions revealed that the three isoforms were expressed in all seven brain regions studied (olfactory bulb, cortex, caudate, hippocampus, thalamus, cerebellum, and brain stem), and there was only about a twofold difference in MT mRNA expression from one region of the brain to another. However, olfactory bulb had the highest mRNA expression for all three isoforms, as revealed by slot blot analysis. Constitutive expression of MT-I and -II mRNA, but not MT-III mRNA, was high in cerebellum. In order to study the cellular localization of MT mRNA, in situ hybridization of MT-I and MT-III mRNA was performed. For comparison, LPS was used to enhance MT-I mRNA signal because LPS is a good inducer of MT-I mRNA expression in mouse brain. In situ hybridization revealed that certain brain regions had distinctly localized high levels of expression of MT mRNAs. In brains of untreated mice, the constitutive expression of MT-I mRNA was high in the ependymal cell layer lining the lateral ventricles and in the Purkinje cell layer of cerebellum. The signal in the Purkinje cell layer was not on the Purkinje cells themselves, but was on locations consistent with that of glial cells. In LPS-treated mice, the signal in cerebellum was higher, and distinct signal appeared in the choroid plexus. However, signal in ependyma was similar to that in untreated mice. Pia mater in LPS-treated, but not in untreated, mouse brain showed enhanced signal for MT-I mRNA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7878671 TI - Correlation between toxicity and effects on intermediary metabolism in 2,3,7,8 tetrachlorodibenzo-p-dioxin-treated male C57BL/6J and DBA/2J mice. AB - Male mice were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by gavage. C57BL/6J (C57) mice received 0.03 to 235 micrograms/kg, DBA/2J (DBA) mice 1 to 3295 micrograms/kg. On Day 8 after dosing blood was collected, and livers and kidneys were removed. Body weights and feed intake were not much affected until Day 8 after exposure. Hepatomegaly developed at doses above 3 and 97.5 micrograms/kg in C57 and DBA mice, respectively. Ethoxyresorufin O-deethylase activity was induced in liver with an ED50 of 1.1 and 16 micrograms/kg and in kidney with an ED50 of 65 and 380 micrograms/kg in C57 and DBA mice, respectively. The activity of phosphoenolpyruvate carboxykinase (PEPCK) in livers of both mouse strains was reduced over the entire dose range, displaying a plateau in the dose response at the onset of acute toxicity of TCDD. This enzyme activity was decreased by as much as 80% at the respective lethal doses. PEPCK activity in kidney was not affected. Glucose-6-phosphatase activity (G-6-Pase) in liver was altered only in the lethal dose range with a maximum reduction of about 50%. Serum glucose concentration was reduced over the entire dose range, but the reduction was significant only at doses in which G-6-Pase activity was affected, reaching levels as low as 3 mmol/liter in DBA mice. Tryptophan 2,3-dioxygenase activity was not lowered at any dose of TCDD in either mouse strain, and no increase in serum tryptophan levels was observed. Serum levels of thyroxine (T4) and triiodothyronine (T3) were dose dependently decreased over most of the dose range administered, with T3 levels exactly paralleling T4 levels in both mouse strains. It is concluded that TCDD causes acute toxicity in male C57 and DBA mice by a severe reduction of gluconeogenesis, but, in contrast to rats, it does not affect tryptophan homeostasis. Following administration of TCDD serum T3 levels in the mouse appear to correlate with T4 levels, whereas in the rat they are independent of each other. PMID- 7878672 TI - In vitro myotoxicity of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, pravastatin, lovastatin, and simvastatin, using neonatal rat skeletal myocytes. AB - Pravastatin, lovastatin, and simvastatin, drugs which lower cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, have been linked to skeletal myopathies in humans and rats. The myotoxicity of these three drugs was compared, after 48 hr exposure, in cultures of primary neonatal rat skeletal myotubes. Measurements included HMG CoA reductase activity ([14C]acetate incorporation into cholesterol), indicators of membrane damage (CPK, LDH, and AST), cell viability (mitochondrial dehydrogenase metabolism of MTT), protein synthesis ([3H]leucine incorporation), and energy status (ATP). All three drugs inhibited cholesterol synthesis to the same extent in rat hepatocytes (IC50s approximately 0.07 microM). Lovastatin- and simvastatin-induced inhibition of cholesterol synthesis in myotubes was unchanged compared to that of hepatocytes, but pravastatin was 85-fold less potent (IC50 = 5.9 microM). Protein synthesis and ATP levels were the most sensitive indicators of toxicity. Pravastatin (IC50 = 759 microM) was > 100-fold less inhibitory of protein synthesis than lovastatin (IC50 = 5.4 microM) or simvastatin (IC50 = 1.9 microM). Addition of mevalonic acid (the immediate product of the HMG CoA reductase reaction), as 100 microM mevalonic acid lactone, reversed the toxicity of all three drugs. Removal of serum for 24-72 hr did not alter the toxicity of any of the drugs compared to cultures containing 10% serum, suggesting that differences in protein binding did not account for the differences in toxicity of the drugs. These results indicate that pravastatin is less myotoxic than lovastatin or simvastatin in this in vitro system using neonatal rat skeletal muscle cells, and this differential toxicity is correlated with the selective decrease in inhibition of HMG CoA reductase by pravastatin in nonhepatic tissues. PMID- 7878673 TI - Fetal, neonatal, and long-term alterations in hepatic retinoid levels following maternal polychlorinated biphenyl exposure in rats. AB - This study was undertaken to investigate the effects of perinatal polychlorinated biphenyl (PCB; Aroclor 1254) exposure on hepatic and plasma retinoid levels in fetal rats, their dams, and neonatal and adult offspring. Pregnant Wistar rats were treated with 0, 5, or 25 mg Aroclor 1254/kg body wt from Days 10 to 16 of gestation. Hepatic retinoid (retinol, retinyl palmitate, and retinyl stearate) levels were determined in fetuses and dams from Day 20 of gestation, in male and female neonates 21 days postpartum, and in young adult offspring 90 days after birth. Retinol levels were determined in fetal and maternal plasma (Gestation Day 20) and plasma from the offspring 21 and 90 days after birth. Maternal and fetal plasma retinol levels were decreased by 35 and 38% on Day 20 of gestation following exposure to the highest dose of Aroclor 1254. Male, but not female, neonatal plasma retinol levels were significantly decreased (23%) in the high dose group. No effects of PCB treatment were seen on plasma retinol levels in the offspring 90 days after birth. Only slight reductions in fetal and maternal hepatic retinol and retinyl palmitate concentrations were observed after prenatal PCB exposure. Male neonatal hepatic retinyl palmitate levels were reduced by 25 and 50% in the 5 and 25-mg Aroclor 1254/kg dose groups, respectively, while female neonatal hepatic retinyl palmitate levels were significantly reduced only in the high-dose group. Ninety days after birth, male hepatic retinyl palmitate levels were only slightly reduced in the highest dose group; however, hepatic retinol concentrations were significantly reduced by 50% in both PCB treatment groups. Female adult offspring exhibited significant reductions in hepatic retinyl palmitate levels (25%) in both PCB treatment groups, while hepatic retinol levels exhibited an unusual increase of more than 100% of controls in the low-dose group, while levels in the high-dose group were similar to controls. This study demonstrates that even a relatively low maternal dose of Aroclor 1254 results in long-term alterations in retinoid status of the offspring in the rat. PMID- 7878674 TI - Induction of newly synthesized proteins in astroglial cells exposed to lead. AB - Although astroglial cells accumulate lead (Pb), they appear to be less sensitive to its overt deleterious effects than are neurons. One possible mechanism in which as rocytes adapt to Pb may be by upregulating the expression of particular genes. This study evaluated the effect of exogenous Pb on proteins synthesized in primary rat astroglial cultures. Following incubations with 0-50 microM Pb acetate cells were radiolabeled with leucine for various time intervals. Proteins were subsequently analyzed using SDS-PAGE followed by fluorography. Changes observed within the first 24 hr resembled a classical stress response and included increased synthesis of proteins with apparent molecular weights of 90, 70, 32-35, and 23 kDa. The most notable change was the enhanced synthesis and abundance of the 23-kDa protein (p23) which persisted throughout a 14-day treatment period, whereas the synthesis of the other proteins declined. This protein did not appear to be induced in rat lung fibroblasts treated with similar concentrations of Pb. Subcellular fractionation indicated that p23 was localized to the cytosol. Treatment with actinomycin D or cycloheximide prior to the addition of Pb precluded induction of p23. Pulse labeling of cells following a 24 hr Pb exposure revealed that p23 continued to be synthesized for 12 but not 24 hr following removal of Pb. Pulse-chase experiments indicated that the protein was stable for at least 18 hr following the removal of Pb. Two-dimensional gel electrophoresis revealed that the 23-kDa Pb-induced protein consisted of multiple charged species with pl values ranging from 4.3 to 7.8. PMID- 7878675 TI - Ozone-induced decrease of mouse tracheal potential is not secondary to cellular inflammation. AB - Acute exposure of C57BL/6J (B6) mice to ozone (O3) causes decreased in vivo tracheal electrical potential difference (PD). To investigate the role of inflammation in this response we measured O3 effects in B6 mice pretreated with indomethacin (5 mg/kg), colchicine (3 mg/kg), or cyclophosphamide (30 mg/kg x 7 days). Mice were exposed to 2 ppm O3 or air for 3 hr and allowed to recover for 0, 3, 6, 9, or 12 hr. Tracheal PD was measured under pentobarbital anesthesia using a capped agar bridge inserted into the upper trachea through a neck incision. After measurement of PD, bronchoalveolar lavage (BAL) was performed and total cells, polymorphonuclear leukocytes (PMNs), and protein were determined. As previously reported, O3 exposure decreased PD and increased BAL total cells, PMNs, and protein. O3-induced changes in PD and PMNs were maximal 6-9 hr after exposure. Indomethacin prevented the O3-induced change in PD but had no effect on BAL total cells or PMNs. Colchicine attenuated O3-induced increases in PMNs and cyclophosphamide decreased O3 effects on both BAL total cells and PMNs but neither drug affected the PD response. None of the drugs significantly altered O3 induced increases in BAL protein. The indomethacin sensitivity of O3-induced changes in PD may reflect a role of cyclooxygenase products in that response. However, drugs known to inhibit PMN function did not affect O3-induced changes in PD. We suggest that cellular inflammation is not required for the tracheal electrophysiological response to acute O3 exposure. PMID- 7878676 TI - Immune effects of hexachlorobenzene in the rat: role of metabolism in a 13-week feeding study. AB - The role of metabolism and porphyria in the immunomodulating effects of hexachlorobenzene (HCB) was investigated. To this end, female Wistar rats received a diet with two different doses of HCB and pentachlorobenzene (PCB), either in combination or not with the cytochrome P450IIIA1 inhibitor, triacetyloleandomycin (TAO). Urinary metabolites and urinary and liver porphyrins were measured at regular intervals and data have been published elsewhere. Skin lesions were scored weekly and after 13 weeks of exposure lymphoid organs were weighed, spleens were examined by morphometry, and serum.(auto)antibody levels were determined by ELISA. The probability of causal relationships between the different parameters was determined by analysis of correlation. HCB caused a dose dependent increase of the incidence, but not the severity, of skin lesions, and dose-dependently increased weights of popliteal lymph nodes and spleen and serum levels of IgM, IgA, and autoantigen-specific IgM. IgG and IgG autoantibody levels were not changed. The splenomegaly could be attributed to an expansion of all splenic compartments. PCB caused no skin lesions and had only minor, predominantly immunosuppressive effects. TAO virtually lacked immunomodulating activity of its own, hardly affected the induction of skin lesions by HCB, did not change the immune effects of HCB, and suppressed IgG levels when combined with PCB. Comparison of the immunological data with those found in the same rats as to induction of porphyria and biotransformation of HCB and PCB, indicates that the HCB-induced porphyria, being markedly reduced by coadministration of TAO, is not involved in the immunomodulating effects of HCB. The same conclusion could be drawn for the oxidative HCB metabolites, since TAO inhibited their formation, while the same metabolites were formed upon administration of PCB that lacked the immunostimulatory effects of HCB. Therefore, HCB itself, its nonoxidative metabolites, or their precursors are likely candidates for inducing the immune effects. Further, an immune component in the HCB-induced skin lesions, usually associated with dermal porphyrin accumulation, is suggested by the observations that TAO profoundly reduced induction of porphyria, but not of skin lesions and immune effects, by HCB. PMID- 7878677 TI - Sulfur mustard-induced increase in intracellular free calcium level and arachidonic acid release from cell membrane. AB - The mechanism of action of the alkylating agent bis-(2-chloroethyl)sulfide (sulfur mustard, SM) was studied using the in vitro mouse neuroblastoma-rat glioma hybrid NG108-15 clonal cell line model. Following 0.3 mM SM exposure, cell viability remained high (> 80% of untreated control) up to 9 hr and then declined steadily to about 40% of control after 20-24 hr. During the early period of SM exposure, when there was no significant cell viability loss, the following effects were observed. The cellular glutathione level decreased 20% after 1 hr and 34% after 6 hr. Between 2 and 6 hr, there was a time-dependent increase (about 10 to 30%) in intracellular free calcium (Ca2+), which was localized to the limiting membrane of swollen endoplasmic reticula and mitochondria, to euchromatin areas of the nucleus, and to areas of the cytosol and plasma membrane. Moreover, there was also a time-dependent increase in the release of isotopically labeled arachidonic acid ([3H]AA) from cellular membranes. Increase in [3H]AA release was 28% at 3 hr and about 60-80% between 6 and 9 hr. This increase in [3H]AA release was inhibited by quinacrine (20 microM), which is a phospholipase (PLA2) inhibitor. At 16 hr after SM exposure, there was a large increase (about 200% of control) in [3H]AA release, which was coincident with a 50% loss of cell viability. These results suggest a Ca(2+)-mediated toxic mechanism of SM via PLA2 activation and arachidonate release. PMID- 7878678 TI - Immunotoxicity of AZT: inhibitory effect on thymocyte differentiation and peripheral T cell responsiveness to gp120 of human immunodeficiency virus. AB - 3'-Azido-2',3'-dideoxythymidine (AZT) is extensively used in the treatment of human immunodeficiency virus (HIV) infection. Currently, it is debated whether AZT should be offered to symptomless HIV-infected individuals in the hope of delaying or even preventing progression to acquired immunodeficiency syndrome (AIDS). However, before the chronic use of AZT, it is essential to establish whether this drug alters the differentiation and functions of T cells particularly because HIV infects CD4+ T cells, as well as investigate whether AZT would alter the T cell response to HIV-encoded antigens. In the current study, therefore, we investigated the effect of administration of AZT into mice for 7-14 days on T cell differentiation in the thymus and the ability of T cells to respond to HIV antigens in the periphery. Our data demonstrated that AZT, when administered orally at 500 mg/kg body wt or higher concentrations for 14 days, caused marked thymic involution with significant decrease in the percentage of CD4+CD8+ T cells and increase in the percentage of CD4-CD8-, CD4+, and CD8+ T cells. AZT treatment did not affect the cellularity of the spleen or the ratios of T cells in the periphery. Also, splenic T cells from AZT-treated mice did not demonstrate marked decrease in their ability to respond to mitogens in vitro. However, when AZT-treated mice were immunized with foreign antigens, such as gp120 of HIV or conalbumin, the T cells demonstrated significant decrease in their ability to respond to these antigens. When AZT was added to cultures, it was found to inhibit the proliferation of T cells to mitogens as well as the differentiation of cytotoxic T lymphocytes (CTL). Interestingly, addition of exogenous IL-2 to CTL cultures reconstituted the decreased CTL response. Furthermore, administration of IL-2 into AZT-treated mice could also reconstitute the decrease in thymic cellularity induced by AZT. These data indicate that AZT, when present at the time of T cell differentiation or responsiveness to antigens in vivo, can mediate significant inhibition of such functions thereby suggesting that AZT may affect the immune response to HIV antigens. PMID- 7878679 TI - Iron-induced lipid peroxidation in rat liver is accompanied by preferential induction of glutathione S-transferase 8-8 isozyme. AB - Since previous studies from this laboratory have suggested that glutathione S transferase (GST) 8-8 of rat belongs to a distinct subgroup of GST isozymes which may be involved in the detoxification of the products of lipid peroxidation (Zimniak et al., J. Biol. Chem. 269, 992-1000, 1994), during the present studies we examined the effect of iron-induced lipid peroxidation on the expression of GST 8-8 in rat liver. Rats treated with 100 mg/kg body wt iron showed a significant increase in lipid peroxidation in liver. This was accompanied by a concomitant increase in the expression of GST 8-8 in liver as observed in isoelectrophoretic analysis of rat liver GSTs, and an increase in GST activity toward 4-HNE, a toxic product of lipid peroxidation toward which GST 8-8 displays high specific activity. Western blot studies using polyclonal antibodies specifically recognizing GST 8-8 also indicated that, among the GST isozymes of rat liver, GST 8-8 was preferentially induced upon iron treatment. These findings were further confirmed by purifying and quantitating GST 8-8 protein from the controls and iron-treated rats. Significant differences in the specific activities of GST 8-8 purified from the controls and iron-treated rats were observed, indicating that more than one GST isozyme related to GST 8-8 may be present in rat liver. This observation is consistent with the observed heterogeneity in mouse mGSTA4-4 which is an ortholog of rat GST 8-8. Iron treatment also caused significant increase in GSH levels probably because of de novo synthesis as indicated by an increase in gamma-glutamyl cysteine synthetase activity. The results of these studies suggest that GST 8-8, and possibly other related GST isozymes, may play an important role in defense mechanisms against lipid peroxidation. PMID- 7878680 TI - Measurement of the hemoglobin N-(2-oxoethyl)valine adduct in ethyl carbamate treated mice. AB - Ethyl carbamate (EC) is bioactivated by CYP2E1 through vinyl carbamate to its epoxide, a reactive electrophile. This carcinogen reacts with macromolecules, including hemoglobin (Hb). This report defines a method to examine levels of N-(2 oxoethyl) adduct on the N-terminal valine of Hb after EC treatment at carcinogenic doses. Concentrations were determined 24 hr following an oral dose of EC (1 mg/g body wt) to strains A/J and C57BL/6 mice. Globin samples were isolated by precipitation in acidified acetone, washed, dried, and stored frozen at -20 degrees C until analyzed. Weighed aliquots were treated with sodium borohydride to reduce the aldehyde of the 2-oxoethyl group to the N-(2 hydroxyethyl) adduct. The adduct valine was cleaved using phenylisothiocyanate to form a substituted phenylthiohydantoin derivative of N-(2-hydroxyethyl)valine in a modified Edman degradation. After reaction with N,O bis(trimethylsilyl)trifluoroacetamide, the resultant product, 1-(2' trimethylsilyloxy)ethyl-5-isopropyl-3-phenyl-2-thiohydantoin , was quantified by GC/MS with selected ion monitoring of the molecular ion using synthetic N-(3 hydroxypropyl)valine as an internal standard. No adducts were detected without NaBH4 reduction. Strain A/J mice treated with EC (1 mg/g, N = 10) yielded mean +/ standard deviation (SD) adduct level values of 13.3 +/- 1.03 nmol/g globin; saline-treated A/J controls (N = 7) gave background levels of 4.43 +/- 0.69 nmol/g globin. Strain C57BL/6 mice treated with EC (1 mg/g, N = 6) exhibited mean +/- SD values of 12.0 +/- 1.92 nmol/g globin, while control mice of this strain (N = 4) had adduct levels of 7.23 +/- 1.19 nmol/g globin. These results are consistent with findings of others that bioactivation of EC produces N-(2 oxoethyl)valine hemoglobin adducts. Although the difference between mouse strains in mean total adduct levels following EC treatment was not significant, the differences evident in comparisons within strains due to treatment, between strains in endogenous background levels, and between strains in estimates of mean increases in adduct concentrations resulting from EC treatment were highly significant (p < 0.01). This assay provides a biomarker system for assessment of production from EC of the electrophilic metabolites which are believed to be genotoxic following metabolic activation in vivo. PMID- 7878681 TI - Effects of supplemental nutrition on lead-induced depression of growth and food consumption in weanling rats. AB - The objective of this study was to determine whether growth-depressant effects of lead (Pb) could be prevented by preventing the accompanying depression of caloric intake from ad libitum food consumption by caloric supplementation. The animal used was the female weanling rat. Three experiments were performed in which progressively increasing levels of caloric supplementation were provided in order to attain a level of nutrition which would totally prevent growth depression from Pb exposure. Nutritional supplementation of Pb-exposed animals almost completely eliminated the Pb-induced depression of weight gains. We conclude that the deficit in growth due to Pb can be adequately explained on the basis of a primary effect on appetite, rather than being secondary to depression of proliferative responses of cells to growth factors, e.g., insulin-like growth factor I. PMID- 7878682 TI - Effects of lead administration on developing rat kidney. I. Glutathione S transferase isoenzymes. AB - The effects of acute and chronic exposure to lead on glutathione S-transferase (GST) isoforms were determined in developing kidney in the rat. The ontogeny of glutathione S-transferase isoforms was characterized as were the effects of depletion of dietary calcium on glutathione S-transferase isoform profiles in control and lead-treated rats. In the acute exposure experiments, rats of 14 and 50 days of age received three daily injections of lead acetate (114 mg/kg) and in the chronic exposure studies, rats received lead acetate at doses ranging from 50 to 500 ppm in their drinking water. Lead acetate administration in these chronic studies began 1 day after conception. Acute and chronic lead exposure had similar effects, causing increases in all but one glutathione S-transferase isoform (Yb3); these increases were markedly exacerbated by dietary calcium depletion. In all lead paradigms, GST subunits Yb1 and Yp showed the largest increases--greater than 25-fold in rats fed a low-calcium diet. GST subunit Yb3 showed small increases in the 14-day acute lead and the 4 week low-calcium animals and did not increase in other groups. Lead-related increases in GSTs were partially reversed by transferring animals previously receiving lead to lead-free water for a 4-week period. Kidneys of rats fed the low-calcium diet did not have detectable GST Yk, but in rats on this low-calcium diet that received 500 ppm lead; this GST isoform was found at levels comparable to those in control rats fed lab chow. PMID- 7878683 TI - Effects of lead administration on developing rat kidney. II. Functional, morphologic, and immunohistochemical studies. AB - The effects of chronic lead administration on renal function and cytoarchitecture and on the immunohistochemical localization of glutathione S-transferase (GST) isoenzymes were determined. Pregnant rats were given 250 ppm lead acetate in drinking water from conception until weaning and mothers and pups received 500 ppm of lead acetate from weaning until termination at either 3 or 7 weeks of age. Light and electron microscopic studies after 3 weeks of lead administration showed tubular injury with frequent mitoses noted in proximal tubular cells and, after 7 weeks of treatment, interstitial fibrosis, characteristic intranuclear inclusions, and tubular injury characterized by both nuclear and cytoplasmic pleomorphism. Rats treated with lead for 7 weeks showed significantly lower body weights and creatinine clearances than age-matched control animals. Immunohistochemical studies of glutathione transferase subunits in control rats showed unique isoform localization in each segment of the nephron; treatment with lead caused large increases in immunoreactive protein of Yc, Yk, Yb1, and Yp GST subunits in proximal tubules. No increases in the antioxidant enzymes copper-zinc superoxide dismutase, catalase, and glutathione peroxidase were found in lead treated rats, but there was a diffuse lead-related increase in immunoreactive protein for manganese superoxide dismutase throughout the renal cortex. Our results demonstrate large lead-induced increases of specific isoforms of glutathione S-transferase in specific kidney cell types and show that these increases preceded irreversible renal damage. PMID- 7878684 TI - Anti-estrogen activity in the yeast transcription system: estrogen receptor mediated agonist response. AB - The mouse estrogen receptor was expressed in yeast cells to study the mechanism of action of anti-estrogens. Tamoxifen and hydroxytamoxifen, estrogen antagonists in mammalian tissues, failed to antagonize estradiol-induced expression of a VitA2-ERE-CTC1-lacZ reporter gene construct and exhibited full agonist activity, while nafoxidine exhibited partial antagonism as well as partial agonism. ICI 164,384 is a potent anti-estrogen in both mouse and human estrogen receptor systems. Our previous studies in the mouse uterus indicated that rapid degradation of the estrogen receptor accounted for the loss of estrogen responsiveness. In yeast however, ICI 164,384 or an isomer ICI 182,780 were unable to antagonize estradiol at concentration of 200 microM. On the contrary, both ICI compounds exhibited partial agonist activity by stimulating beta galactosidase activity to 50% that of estradiol. We examined the level of estrogen receptor in the yeast after treatment with estradiol, ICI 164,384 or vehicle by Western blot and found no ICI-induced reduction of estrogen receptor levels, but observed an increase in estrogen receptor following estradiol treatment. This indicates that the proteolytic activity responsible for degrading estrogen receptor in ICI 164,384-treated uteri or eukaryotic cells is not present in yeast. The agonist activity seen with ICI indicated that ICI-bound estrogen receptor is able to induce expression of an estrogen-responsive reporter gene. In support of this, estrogen receptor from ICI 164,384-treated yeast was able to bind an estrogen-responsive element in a gel-shift assay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878685 TI - A- or B-ring-substituted derivatives of androst-4-ene-3,6,17-trione as aromatase inhibitors. Structure-activity relationships. AB - 2,2-Dimethylandrost-4-ene-3,6,17-trione (5) and its 4-methoxy- (7) and 4-hydroxy- (8) derivatives were synthesized. 7 alpha-Acetoxy-4-ene-3,6-dione steroid 2 was also prepared by the improved method involving the lead tetraacetate oxidation of androst-4-ene-3,6,17-trione (1). These steroids along with the 2-acetoxy-(11 and 12), 2-substituted 1-ene- (9 and 10), and 4-substituted (13-15) derivatives of compound 1 were evaluated as inhibitors of human placental aromatase. All the steroids, except the 2-acetoxy-1-ene 10 and the 2 beta-acetate 11 of which Ki values were not determined because of their poor inhibitory activities, blocked aromatase in a competitive manner. Compounds 5 and 8 as well as the 4-hydroxy steroid 15 were potent inhibitors (Ki: 25-42 nM) whereas the inhibitory activities of steroids 2, 7, 9, 13, and 14 were good to fair, respectively (Ki: 160-810 nM). Inhibitors 2 and 15 inactivated the enzyme in a time-dependent manner in the presence of NADPH but the 2,3-dimethyl derivatives 5 and 8 did not. Androstenedione blocked the inactivation but L-cysteine did not. The results suggest that the 2 beta-methyl group would prevent the aromatase-catalyzed oxygenation at C-19 of the dimethyl steroids 5 and 8 most likely through the steric reasons. PMID- 7878686 TI - Synthesis and radiochemistry of 2,4-disubstituted 17 alpha-iodovinylestradiols. AB - This report details the preparation of three compounds which are structurally designed to have depressed metabolism and/or conjugation: 2,4-dibromo-, 2,4 dichloro-, and 2,4-dimethyl-17 alpha-iodovinylestradiol. Their synthesis includes the use of two novel transformations based upon tin chemistry: preparation of an intermediate 17 alpha-vinylstannanes via stannylcupration of a 17 alpha-ethynyl steroid, and preparation of the 2,4-dimethyl functionality via a palladium catalyzed coupling of 2,4-dibromoestrone acetate with tetramethyltin. The preparative radiochemistry of these three materials is also described. PMID- 7878687 TI - Binding kinetics of fluticasone propionate to the human glucocorticoid receptor. AB - Receptor-ligand interactions of fluticasone propionate (FP), a glucocorticoid used for inhalation therapy, were determined and compared with dexamethasone, budesonide, and beclomethasone-17-monopropionate, the active metabolite of beclomethasone dipropionate. Two approaches, evaluation of binding kinetics and competition assays, were applied to obtain relative receptor affinities (RRAs) with dexamethasone as reference. A higher association rate constant and a distinctly lower dissociation rate constant for FP compared with the other glucocorticoids resulted in an equilibrium dissociation constant (Kd) of 0.49 nmol/l. Kd dexamethasone was 9.36 nmol/l; derived RRA of FP was 1910. The calculated half-time of the FP-receptor complex was 10 h, thus exceeding the half times of all other glucocorticoids as well as their RRAs. Competition assays clearly confirmed the rank order of the tested glucocorticoids, although RRAs were generally lower than those found in kinetic assays and strongly dependent on the assay conditions. The high receptor affinity of FP is reflected by clinical trials demonstrating its superiority to other glucocorticoids. For therapeutic application, the long half-time of the FP-receptor complex should support the practicality of longer dose-intervals. PMID- 7878688 TI - Corticosteroid-binding globulin mRNA levels in human uterine endometrium. AB - Corticosteroid-binding globulin (CBG or transcortin) is a specific plasma glycoprotein, which binds steroid hormones (cortisol, corticosterone, and progesterone), and plays a role in transporting these steroids, altering their concentrations in blood, and influencing their biological actions. CBG has been previously shown to be synthesized in the liver, but recently it has been reported that immunoreactive CBG is localized in target tissues. In the present work, CBG mRNA was detected in normal human endometrial tissues by Northern blot analysis and reverse transcription-polymerase chain reaction. Its level was higher (P < 0.05) in the secretory phase than in the proliferative phase. In the secretory phase, the endometrial CBG mRNA level was negatively correlated with the serum progesterone level (P < 0.01). While there was no positive correlation between the levels of endometrial CBG mRNA and serum estradiol (E2), there was a positive correlation between the endometrial CBG mRNA level and the serum E2/progesterone ratio (P < 0.05). These findings suggest that CBG is synthesized in the uterine endometrium, predominantly in the secretory phase, and that the serum E2/progesterone ratio exerts an influence on the synthesis of intracellular CBG. PMID- 7878689 TI - Hadd reference collection of steroid glucuronides. PMID- 7878690 TI - Carbamazepine and its epoxide: an open study of efficacy and side effects after carbamazepine dose increment in refractory partial epilepsy. AB - We evaluated the efficacy, development of adverse effects, and possible correlation between the plasma concentration of carbamazepine (CBZ) and its major metabolite, carbamazepine-10,11-epoxide (CBZ-E), in a group of epileptic patients in whom selective increases in CBZ doses were made. Eighteen patients with refractory partial epilepsy participated in an open trial. Five were on monotherapy and 13 on polytherapy. All the patients were on CBZ before the trial and had plasma levels within the therapeutic range (17-42 mumol/L). After a baseline period, CBZ doses were progressively increased either to reach a 50% reduction in seizure frequency for 2 months or until side effects appeared. Thirty-nine percent of the patients had a 50% decline in seizure frequency, but only 17% improved for > 6 months. Mild or moderate side effects were observed in 78% of the patients. Side effects were correlated with CBZ plasma levels but not with CBZ-E plasma levels. Correlation between CBZ and CBZ-E plasma levels were found in the monotherapy group, but not in the polytherapy group. Our results confirm that higher doses of CBZ can successfully be used in some patients with refractory partial epilepsy. Furthermore, the plasma level of CBZ-E does not seem to be a useful indicator of toxicity in CBZ-treated ambulatory epileptic patients. PMID- 7878691 TI - Search for a therapeutic range for serum zuclopenthixol concentrations in schizophrenic patients. AB - The aim of our study was to find a therapeutic range for the serum concentration of zuclopenthixol (S-Zu) in chronic schizophrenic patients. S-Zu was measured in 17 patients and dosage reduction was suggested by the laboratory if S-Zu exceeded 15 nmol/L. The clinical symptoms and side effects were evaluated blindly using the Brief Psychiatric Rating Scale (BPRS) and the UKU rating scale, respectively. S-Zu and ratings were repeated 6, 12, and 24 weeks after the final dosage adjustments. In 7 of 10 patients with S-Zu > 15 nmol/L the dosage was reduced by 20-67%. After dosage reduction the S-Zu was below 15 nmol/L in 10 of the 17 patients. The mean BPRS score and the side effects, evaluated by the UKU scale, were reduced in patients in whom the dosage was reduced. It is suggested that S Zu in the range 5-15 nmol/L may serve as a preliminary therapeutic range for S Zu. PMID- 7878692 TI - Lack of interaction of erythromycin with temazepam. AB - Erythromycin is a strong inhibitor of cytochrome P450 [CYP3A4] and has a potentially dangerous interaction with midazolam and triazolam. The possible interaction between erythromycin and a short-acting benzodiazepine, temazepam, was investigated in a double-blind, randomized crossover study. Ten healthy volunteers received 500 mg erythromycin or placebo orally three times a day for 6 days followed by a challenge dose of 20 mg temazepam. Plasma samples were collected for the determination of temazepam, oxazepam, and erythromycin, and psychomotor effects were measured during the 24 h after intake of temazepam. Erythromycin did not change the pharmacokinetics or pharmacodynamics of temazepam to a statistically significant degree. The metabolic fate of temazepam and its almost complete bioavailability explain the lack of interaction. Temazepam, unlike midazolam or triazolam, can thus be prescribed in the usual doses for patients receiving erythromycin. PMID- 7878693 TI - Population pharmacokinetic models: effect of explicit versus assumed constant serum concentration assay error patterns upon parameter values of gentamicin in infants on and off extracorporeal membrane oxygenation. AB - Prior authors had hypothesized (but not clearly found) an increased apparent volume of distribution (Vd) for gentamicin in neonates undergoing extracorporeal membrane oxygenation (ECMO). We chose to study the question in our own clinical setting. To develop population pharmacokinetic models of the drug, we used the nonparametric expectation and maximization population modeling method and data from 11 neonates who received gentamicin on ECMO, including 6 infants who received gentamicin both on and off ECMO for severe respiratory failure. We found an increased Vd for gentamicin on ECMO and attributed much of the difference from prior investigations to our use of an explicitly determined laboratory assay error pattern for the measured serum concentrations rather than using constant weighting of the serum level data points. For six infants, while on ECMO their median Vd was 0.748 L/kg compared with a median Vd of 0.471 L/kg after ECMO was discontinued. The median clearance of gentamicin in the six infants while undergoing ECMO was 0.239 L/h compared with 0.350 L/h after ECMO was discontinued. The median half-time (T1/2) was 9.24 h while on ECMO compared with 3.87 h when off ECMO. We conclude that while undergoing ECMO, neonates have a higher volume of distribution for gentamicin, a lower clearance, and a much longer half-life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7878694 TI - Methotrexate in rheumatoid arthritis--a limited sampling strategy for estimation of the area under the plasma concentration versus time curve. AB - A limited sampling strategy for determination of the area under the plasma concentration versus time curve (AUC) of methotrexate (MTX) in patients with rheumatoid arthritis (RA), treated with weekly oral doses, has been validated. Stepwise linear regression analysis was used for optimal inclusion of data points in mathematical models to estimate AUC. A new plot for evaluation of the accuracy and precision of the estimated AUC values was introduced in the present study. By plotting the ratio of determined/estimated AUC values versus estimated AUC values, the influence of number of sampling points on the precision and accuracy of estimated AUC values was easily validated. Our results show that AUC values of MTX in RA patients can be estimated from a single plasma sample at 3 h or preferably, due to increased precision, by additional samplings at 5 and 1 h. A further increase of the number of sampling points increased the precision of the AUC estimates only to a minor extent. The accuracy of the estimated AUC values was independent of the number of sampling points. A limited sampling procedure can now be used for further studies on the relationship between MTX levels and its effects. PMID- 7878695 TI - Australian cyclosporin therapeutic monitoring method survey: 1993. AB - A detailed questionnaire was distributed to the 30 Australian laboratories known to provide cyclosporin-A (CsA) therapeutic drug monitoring (TDM) services with a view to evaluating the range of approaches to such monitoring. Replies were received from all 30 laboratories. The data suggested there was a wide discordance in approaches to CsA TDM due to the fact that laboratories appeared to have adopted individual approaches to this service, both in method selection(s) and proposed therapeutic range(s). In many cases, patients served were shown to travel to more distant centers for their graft, returning to their home city/town for longer term management. Hence, services of several laboratories were involved during their clinical care. A strong mandate was received from respondents for development of national guidelines for the monitoring of CsA and other immunosuppressant drugs in order to avoid such discrepancies in the future. The approaches to external analytical quality assurance (QA) and, to a lesser extent, internal quality control (QC) were generally inadequate. PMID- 7878696 TI - Cyclosporin A monitoring in Australia: consensus recommendations. AB - Cyclosporin-A (CsA) therapeutic drug monitoring plays an integral role in therapeutic management of immunosuppressed patients, including those with organ transplants. This communication, prepared by an Australian team, presents recommendations for the routine monitoring of CsA, including blood sampling methodological approaches and interpretation of results generated. The consensus approach described is intended to address the diversity of attitudes to CsA monitoring demonstrated in a recent national survey of Australian laboratories that provide CsA analyses. PMID- 7878697 TI - Immunoassay reagents for psychoactive drugs. Part 5. Quantitative determination of imipramine and desipramine by fluorescence polarization immunoassay. AB - Two methods for the quantitative determination of imipramine (IMI) and desipramine (DMI) by fluorescence polarization immunoassay (FPIA) are described. One immunoassay allows for the accurate quantification of imipramine in the presence of desipramine, while the other allows for the accurate quantification of desipramine in the presence of imipramine. PMID- 7878698 TI - Stability of indocyanine green in human serum stored at -20 and -70 degrees C. AB - The stability of indocyanine green (ICG) in human serum after storage at -20 and 70 degrees C for an extended time was studied. Serum samples were fortified with ICG at 6.5, 2.0 and 0.3 microgram ml-1, aliquoted, and frozen at -20 or -70 degrees C. The analytic methodology used an internal standard and separation on a reverse phase liquid chromatographic column with UV detection at 240 nm. Samples were prepared for analysis by protein precipitation with acetonitrile. The assay was stability indicating as shown by the complete loss of the ICG peak upon storage at -20 degrees C for 8 weeks. ICG was not stable, as determine by a t test, for 1 week in human serum when stored at -20 degrees C. Storage at -70 degrees C improved stability but the ICG concentration began to fall steadily after 4 weeks of storage. PMID- 7878699 TI - Rapid simultaneous determination of lidocaine, bupivacaine, and their two main metabolites using capillary gas-liquid chromatography with nitrogen phosphorus detector. AB - A gas-liquid chromatographic method for the simultaneous measurement in serum of bupivacaine, lidocaine, and their main metabolites, 2,6-pipecolylxylidide (PPX) and monoethylglycine xylidide (MEGX), respectively, is described. The procedure involves a one-step extraction and injection of the extract into a gas chromatograph equipped with a capillary column and nitrogen phosphorus detector under constant temperature conditions. Recovery of all components averaged 94%, with the lowest detection limit of 15 ng/ml for the four drugs. The precision within-series coefficients of variation ranged from 7.7% for bupivacaine, 8.6% for lidocaine, 10.2% for MEGX, and 15.8% for PPX. The interday coefficients ranged from 0.7 to 6.5%. Concomitant use of caffeine and carbamazepine may interfere with MEGX and bupivacaine determination, respectively. For this reason, in patients receiving one of these two drugs (or ingesting foods and beverages containing caffeine), the described method is not recommended. PMID- 7878700 TI - Determination of itraconazole and its active metabolite in plasma by column liquid chromatography. AB - Itraconazole is a new triazole antifungal agent. Active orally, this drug is effective against a wide range of fungal pathogens that includes Aspergillus species, and its use in leukemic and AIDS patients is currently on the increase. Oral itraconazole absorption presents up to threefold interindividual variation in man and is reduced in AIDS patients. Consequently an individual itraconazole adjusting dosage is necessary to ensure adequate clinical antifungal activity. Itraconazole undergoes extensive metabolism and the main isolated metabolite, hydroxyitraconazole, is found in plasma at concentrations 2-3-fold higher than parent drug and presents in vitro the same antifungal activity. At present, despite the contribution of this metabolite to the overall activity of the drug, no well-documented assay was reported in the literature for the codetermination of itraconazole and hydroxyitraconazole in plasma. Due to the wide variety of coadministered drugs to patients receiving itraconazole, the purpose of the developed method was to obtain a specific assay sensitive enough for itraconazole therapeutic monitoring. Therefore, a three-step liquid-liquid extraction procedure following by reversed-phase chromatography and spectrofluorimetric detection was performed. This assay allowed determination of 20 ng/ml of both itraconazole and its active metabolite with an acceptable precision using a 0.5 ml plasma sample; no analytic interference was encountered from 45 coadministered drugs tested. PMID- 7878701 TI - Blood distribution of mycophenolic acid. AB - RS-61443 (RS) a morpholinoethyl ester of mycophenolic acid (MPA), can be considered a prodrug, as immunosuppressive activity is expressed only after hydrolysis to MPA upon absorption. Little is known about the blood distribution of MPA; such information would have an impact on the medium used for analysis of the drug in clinical trials. This was investigated by spiking whole blood having an initial temperature of either 4 degrees or 22 degrees C with increasing amounts of MPA ranging from 100 to 10,000 micrograms/L. These drug concentrations span the range seen when immunosuppressive doses of the RS are administered. This was followed by incubation of the blood at 37 degrees C for 0-120 min prior to separation of the cells. The drug concentration was measured in the plasma and whole blood fractions by high-performance liquid chromatography. MPA was almost exclusively found in the plasma fraction and did not exhibit any temperature or concentration dependence. The free or unbound fraction of MPA over the same concentration range was determined by ultracentrifugation and demonstrated a concentration dependence ranging from 7.2 to 16.5% of total drug for a concentration range spanning 500-10,000 micrograms/L. The drug was found to be primarily associated with the non-albumin proteins in the plasma. Less than 10% of the drug was found to be bound to lipoproteins. The data suggest that from an analytical standpoint, plasma, rather than whole blood, would be the most suitable medium for analysis because of the higher concentrations of the drug found in this fraction. PMID- 7878702 TI - Comparison of phenytoin and carbamazepine serum concentrations measured by high performance liquid chromatography, the standard TDx assay, the enzyme multiplied immunoassay technique, and a new patient-side immunoassay cartridge system. AB - Steady-state concentrations of phenytoin (PHT) and carbamazepine (CBZ) were measured by a novel patient-side immunoassay system with a single-use cartridge (Biotrack 516). The Biotrack determinations were performed in whole blood and extrapolated to serum on the basis of the hemoglobin content. The results were compared with serum concentrations measured by high-performance liquid chromatography (HPLC) or the standard TDx and enzyme multiplied immunoassay (EMIT) techniques. A total of 222 samples from epileptic patients on PHT and 322 samples from patients on CBZ were analyzed. In the case of PHT there was a highly linear correlation [r = 0.985, y = 1.113x-0.589; x = HPLC, y = Biotrack] between HPLC and the Biotrack system in the concentration range of 2.5-30 micrograms/ml. In the case of CBZ, the correlation between HPLC and the Biotrack system in the concentration range of 2.0-20 micrograms/ml was somewhat lower [r = 0.931, y = 1.29x-0.136; x = HPLC, y = Biotrack]. Comparable results were also found for the correlation of the Biotrack system with the TDx assay or with the EMIT assay, respectively. Comedication had no influence, or only a minor influence (valproic acid), on the concentration of PHT and CBZ measured by the Biotrack system. Furthermore, the concentration of the metabolite carbamazepine-10, 11-epoxide had no influence on the concentration of CBZ measured by the Biotrack system. Since the automated cartridge system is simple, can be used rapidly, and is performed with only a few drops of blood, this technique offers some advantages for routine clinical use, especially under outpatient conditions. PMID- 7878703 TI - Effect of heating sera under conditions necessary for deactivation of human immunodeficiency virus on commonly monitored therapeutic drugs. AB - Minimizing the risk of infection of laboratory staff from contaminated blood samples is a major safety goal in a clinical laboratory. One dangerous pathogen, the human immunodeficiency virus (HIV) can be deactivated by heating sera at 56 degrees C for 30 min. We studied the effect of such heat treatment on serum concentrations of 11 commonly monitored therapeutic drugs. We used blood specimens collected in serum separator tubes (SSTs), which were routinely submitted for therapeutic drug monitoring in our laboratory for this study. Concentrations of digoxin in sera were measured using a fluorescence polarization immunoassay (FPIA), while concentrations of tobramycin, gentamicin, vancomycin, theophylline, valproic acid, procainamide, N-acetylprocainamide (NAPA), phenytoin, phenobarbital, and carbamazepine were measured by enzyme-multiplied immunoassay technique assays using a Monarch 2000 analyzer. We observed no significant change in the concentration of any drug except phenytoin and carbamazepine following heating at 60 degrees C. The decrease in concentration of phenytoin and carbamazepine after heating was related to absorption of the drug to the gel rather than the instability of the drug under heating conditions. We conclude that blood contaminated with HIV may be deactivated by heating prior to analysis for most of the routinely monitored therapeutic drugs. PMID- 7878704 TI - Therapeutic drug monitoring of phenytoin in patients with the acquired immunodeficiency syndrome. AB - Serum phenytoin concentrations were investigated in 109 serum samples from 21 patients with the acquired immunodeficiency syndrome (AIDS) and in 1,231 serum samples from 557 control subjects during phenytoin therapy. Total phenytoin concentrations were significantly lower in patients with AIDS than in the reference population (8.8 +/- 0.7 mg/L (mean +/- SE) vs. 10.6 +/- 0.2 mg/L), although phenytoin doses were significantly higher in the AIDS patients. Body weight and the use of folic acid were negatively related to phenytoin concentrations, whereas use of clarithromycin resulted in higher phenytoin levels. Zidovudine did not influence phenytoin levels. Calculation of the Michaelis-Menten parameters showed that Vmax values were similar in seven human immunodeficiency virus (HIV)-infected patients as compared with 12 controls, but a nonsignificant trend of lower Km values in the HIV-positive group was observed. Measurement of free phenytoin concentrations demonstrated that the fraction of unbound drug was increased in patients with AIDS. Hypoalbuminemia was common in this population, which may complicate the interpretation of total phenytoin concentrations. PMID- 7878705 TI - Ethosuximide enantiomers in pregnancy and lactation. AB - A gas-chromatographic method was used to determine plasma concentrations of the ethosuximide enantiomers during three pregnancies in two epileptic women, in samples from the umbilical cord in one, and in breast milk in two patients. The ratio of the two enantiomers of ethosuximide ranged from 1.00 to 1.36 and was apparently unaffected by pregnancy, passage into breast milk, and transfer over the placenta. Hence, determination of total ethosuximide concentrations appear to be sufficient for therapeutic drug monitoring during pregnancy and lactation. PMID- 7878706 TI - Phenytoin and plasmapheresis: importance of sampling times and impact of obesity. AB - The effect of plasmapheresis (PP) on total and free phenytoin clearance is reported. An obese patient with the diagnosis of thrombotic thrombocytopenic purpura (TTP) was treated with PP. Twelve episodes of PP, having exchange volumes of 1.5-2.25 times the plasma volume with a mean +/- SD 7.7 +/- 0.8 L of plasma removed, were studied. A significant (p < 0.05) difference was observed with a mean change in plasma phenytoin concentrations from pre- to end-PP of 7.32 +/- 2.5 mg/L compared to 1.98 +/- 0.7 mg/L observed pre-PP to 1 h post-PP. These values corresponded to 48.4 +/- 11.6 and 15.0 +/- 6.7% decreases in phenytoin concentrations at the two aforementioned time periods. To prevent misinterpretation of plasma phenytoin concentrations, samples should not be obtained for at least 2 h after PP. PMID- 7878707 TI - Calibration curves: calculation and evaluation of accuracy. PMID- 7878708 TI - Molecular diagnostics in transfusion medicine: the best is yet to come. PMID- 7878709 TI - Scaling the heights. PMID- 7878710 TI - Cytokine generation in stored, white cell-reduced, and bacterially contaminated units of red cells. AB - BACKGROUND: Proinflammatory cytokines were measured in the supernatant portion of stored, bacterially contaminated, and/or white cell (WBC)-reduced units of red cells (RBCs). Previous studies from this laboratory and others have shown that cytokines are generated in platelet concentrates during storage. This earlier work has been expanded to the study of stored RBCs. STUDY DESIGN AND METHODS: Units of AS-1 RBCs (n = 10 non-WBC-reduced; n = 10 WBC-reduced) were obtained from a regional blood center, and each was split on Day 3 of storage into three equal portions by sterile techniques. One portion was kept sterile (control), and the other two were inoculated with Yersinia enterocolitica and Staphylococcus aureus, respectively, at 1 to 3 colony-forming units per mL. The RBCs were stored at 1 to 6 degrees C for 42 days. Sequential samples were taken during storage and assayed for interleukin 8 (IL-8), interleukin 1 beta (IL-1 beta), interleukin 6, WBC count, and bacteria count. For the WBC-reduced group (n = 10), WBC removal was done by filtration on Day 3 of storage, before bacterial inoculation. RESULTS: IL-8 was detected in the supernatant portion of all 42-day-old, non-WBC reduced (mean WBCs = 4760 +/- 3870/microL) units of AS-1 RBCs at levels ranging from 63 to 1610 pg per mL. By contrast, at 2 to 3 days of storage, lower levels of IL-8 (range, 0-280 pg/mL) were detected in the same units. IL-8 levels increased progressively during storage in most (7/10) units. The highest mean levels of IL-8 were reached by outdate at Day 42. Y. enterocolitica-contaminated units had statistically higher levels of IL-8, with a range of 170 to 2100 pg per mL, by 42 days of storage. S. aureus grew poorly in stored units of RBCs and failed to further stimulate cytokine production. No WBC-reduced unit (mean WBCs = 0.5 +/- 0.6/microL), even when contaminated with bacteria, had more than 260 pg per mL of IL-8. Although IL-1 beta was not detected in any unit of RBCs at 3 days of storage, it increased to low levels (5-13 pg/mL) in all units tested at 42 days. Interleukin 6 was not detected in any unit at any storage time. CONCLUSION: IL-8 and IL-1 beta accumulated in the supernatants of stored RBCs despite cold storage conditions. IL-8 reached levels > 1000 pg per mL in the supernatants of some RBC units. IL-1 beta increased to significant but low levels (< 13 pg/mL). WBC filtration early in storage prevented the accumulation of IL-8. The physiologic significance to transfusion recipients of IL-8 in RBC supernatants is currently unknown and deserves further investigation. PMID- 7878711 TI - Low risk of viral infection after administration of vapor-heated factor VII concentrate or factor IX complex in first-time recipients of blood components. International Factor Safety Study Group. AB - BACKGROUND: Vapor-heated human factor VII concentrate and human factor IX complex are both obtained from prothrombin complex, undergo similar methods of manufacture, and are subjected to an identical two-step vapor-heating process for virus inactivation. STUDY DESIGN AND METHODS: Intermediate-purity vapor-heated human factor VII concentrate and vapor-heated human factor IX complex were monitored for safety with regard to viral infection in the context of an International Factor Safety Study, a prospective study that follows the revised recommendations from the International Congress of Thrombosis and Hemostasis (ICTH). Because the rarity of the respective hereditary deficiencies would have made separate analyses unrealizable, the results were combined for the final analysis. Entry required that patients have no history of transfusion with any blood derivative. After the first infusion of the study drug, patients were monitored for 6 months for the development of non-A, non-B hepatitis (NANBH) and infection with hepatitis B virus (HBV) and for 15 months for infection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). An event was defined as a positive result on any test for any infection. An alanine aminotransferase level more than 2.5 times the upper limit of normal on two consecutive occasions was defined as an event for NANBH. HBV infection was monitored with tests for three different HBV markers: the HBV surface antigen, antibody against the HBV surface antigen, and antibody against HBV core antigen. HCV and HIV infection were monitored with tests for HCV and HIV antibodies. RESULTS: The 25 patients who completed the study (1 has not completed the study and 1 dropped out) received a total of 434 infusions comprising 17 different production lots of the concentrates. Twenty patients were analyzable for NANBH and 25 for HCV and HIV infection. Since most patients had been given HBV vaccination, only 4 patients were analyzable for this end point. None of the patients showed evidence of having developed an event. These data satisfy ICTH criteria when the products are considered together, but vapor-heated factor VII concentrate does not qualify alone because there were only five patients in this group. CONCLUSION: Vapor-heated factor VII concentrate and vapor-heated factor IX complex are associated with a low risk of viral infection. Preliminary results are also presented, indicating that the concentrates are safe with regard to inhibitor development. PMID- 7878712 TI - Reduction in transmission of hepatitis C after the introduction of a heat treatment step in the production of C1-inhibitor concentrate. AB - BACKGROUND: The transmission of viral infections via protein concentrates made from a large pool of plasma depends on the selection of donors, fractionation process, and virucidal methods. To date, no data are available on the infectivity risk of plasma concentrates of the inhibitor of the first component of complement (C1-INH). STUDY DESIGN AND METHODS: The prevalence of blood-borne viral infections and levels of transaminases were evaluated in patients treated with a large-pool plasma concentrate of the inhibitor of C1-INH before and after the introduction of virucidal methods. The study included 85 patients with hereditary angioedema and 4 with acquired angioedema. The patients were divided into three groups: 1) 48 untreated patients; 2) 22 patients treated with non-virus inactivated C1-INH concentrates; and 3) 19 patients treated with virus inactivated concentrates. Serum samples obtained at various times after the infusion of concentrate were assayed for alanine amino-transferase and tested for hepatitis B surface antigen and antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (anti-HIV); anti-HCV-negative subjects exposed to the concentrate were also tested for HCV RNA. RESULTS: Prevalences of HCV infection and elevated alanine aminotransferase are significantly lower in patients treated with virus-inactivated concentrates than in those exposed to non virus-inactivated concentrates. No patients were anti-HIV positive. CONCLUSION: This study suggests that C1-INH concentrates transmitted HCV, but that the virucidal methods adopted are effective in reducing the infectivity. PMID- 7878713 TI - Detection of antibodies to Trypanosoma cruzi among blood donors in the southwestern and western United States. I. Evaluation of the sensitivity and specificity of an enzyme immunoassay for detecting antibodies to T. cruzi. AB - BACKGROUND: Chagas' disease or American trypanosomiasis, caused by infection with Trypanosoma cruzi, is a significant health problem in Latin America. In the United States, transfusions of T. cruzi-contaminated blood from Latin American immigrants may represent the major source of Chagas' disease. STUDY DESIGN AND METHODS: A new enzyme immunoassay (EIA) for the detection of antibody to T. cruzi was evaluated in the sera of blood donors from the southwestern and western regions of the United States. Serum samples had been screened and were negative for all tests required. Specimens that were repeatedly reactive in the Chagas antibody EIA were analyzed for seroreactivity by a confirmatory EIA and by radioimmunoprecipitation assay. RESULTS: Fourteen of the 13,309 donor samples (0.105%) were confirmed as being positive for antibody to T. cruzi. The Chagas antibody EIA showed improved sensitivity over the Chagas IgG enzyme-linked immunosorbent assay and two indirect hemagglutination assays. The Chagas antibody EIA had a specificity of 99.98 percent with negative samples. The sensitivity of the Chagas antibody EIA was 100 percent (80/80) in xenodiagnosed specimens and 100 percent (50/50) in specimens positive by consensus (i.e., reactive in EIA, indirect hemagglutination assay, and immunofluorescence assays). CONCLUSION: This Chagas antibody EIA meets the need for accurate and rapid identification of seroreactive samples in low-prevalence or endemic populations. PMID- 7878714 TI - Detection of antibodies to Trypanosoma cruzi among blood donors in the southwestern and western United States. II. Evaluation of a supplemental enzyme immunoassay and radioimmunoprecipitation assay for confirmation of seroreactivity. AB - BACKGROUND: Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is endemic to Latin America and may be transmitted in the United States via blood donated by infected immigrants. Blood-borne pathogens such as T. cruzi require supplemental testing for confirmation of seroreactivity. STUDY DESIGN AND METHODS: A study was undertaken to determine an optimal scheme for confirmation of seroreactivity in repeatedly reactive samples identified by the Chagas antibody enzyme immunoassay (EIA). The procedure for initial confirmation involves three purified antigens coated onto three separate polystyrene beads and uses an EIA format. If the sample is reactive with two of three or three of three antigens, it is confirmed as seroreactive. If none or one of three beads is reactive, the sample is indeterminate and subjected to a radioimmunoprecipitation assay (RIPA). The RIPA must demonstrate characteristic bands at 32, 34, and 90 kDa. RESULTS: When tested with sera from persons with potentially cross-reactive diseases (n = 39) or against a presumed negative population from southeast Wisconsin (n = 289), the confirmatory EIA had a specificity of 100 percent. Sensitivity was 100 percent (28/28) with xenodiagnosis-positive sera and 97.6 percent (80/82) with chagasic sera from Latin America. The RIPA showed a specificity of 100 percent in EIA-nonreactive samples (n = 100) and a sensitivity of 100 percent with both xenodiagnosis-positive (28/28) and chagasic (82/82) sera. CONCLUSION: The confirmatory EIA and the RIPA together provide a highly specific and sensitive means of confirming seroreactivity for antibodies to T. cruzi. PMID- 7878715 TI - Prevention of transfusion-associated Chagas' disease by sterilization of Trypanosoma cruzi-infected blood with gentian violet, ascorbic acid, and light. AB - BACKGROUND: Allogeneic blood transfusions are the second most frequent route of Chagas' disease transmission in countries where the disease is endemic. The prevention of transfusion-associated Chagas' disease has been attempted through clinical and serologic screening of blood donors and/or by the addition of trypanomicidal substances such as gentian violet (GV) to stored blood for 24 hours. The present study describes an alternative method of chemoprophylaxis of transfusion-associated Chagas' disease that reduces the sterilization time by using a combination of low-concentration GV, ascorbic acid (AA), and photoradiation with visible light. STUDY DESIGN AND METHODS: To better reproduce the conditions of blood transfusion in developing areas, normal human blood was collected in blood collection bags, infected with different concentrations of Trypanosoma cruzi, and treated with GV, AA, and photoradiation. Mice were then inoculated with the T. cruzi-infected human blood that had been stored at different incubation intervals. Active parasites were sought in mouse blood for parasitologic diagnosis and serologic evaluation (mice inoculation, blood culture, and indirect immunofluorescence). RESULTS: The association of GV (250 micrograms/mL), and photoradiation with visible light (75W) sterilized T. cruzi infected blood even after treatment for less than 30 minutes and even when chagasic blood was treated with low-concentration GV (62.5 micrograms/mL for 30 min). Moreover, the trypanomicidal activity of GV associated with AA and photoradiation with visible light was found even when blood was infected with a 10-fold parasite concentration. CONCLUSIONS: The proposed alternative prophylactic method is reproducible, easy to perform, and inexpensive, and it may have practical importance in endemic areas where serologic screening of donor blood is not always available. In addition, the reduction of the GV trypanomicidal concentration might further minimize the potential for GV-related side effects. PMID- 7878716 TI - Determination of ABO glycosyltransferase genotypes by use of polymerase chain reaction and restriction enzymes. AB - BACKGROUND: The molecular basis of red cell ABO group antigens has been determined. The genes encoding the group A and B glycosyltransferases and a nonfunctional group O transferase have been cloned and sequenced. All three genes were similar. When compared to the nucleotide sequence of the A gene, the O gene has a one-base deletion that leads to a frame shift and results in a nonfunctional protein. The B gene differs from the A gene at seven nucleotides. STUDY DESIGN AND METHODS: Techniques using polymerase chain reaction and restriction enzymes to determine ABO transferase genotypes from white cell DNA were modified. Nucleotide sequence differences within the genes were analyzed by the application of selected restriction enzymes. Restriction enzymes Asp718 and BstEII were used to analyze the genes at nucleotide 258, and BssHII and Kas I were used to analyze the genes at nucleotide 523. ABO red cell phenotypes were compared in 60 unrelated individuals with ABO transferase genotypes. The ABO phenotypes and genotypes of individuals from two different families were also analyzed to determine if this method could distinguish individuals who were homozygous for A or B transferase genes from those who were heterozygous. RESULTS: The phenotypes and genotypes were consistent for all unrelated individuals, and within the families, heterozygous individuals could be distinguished from homozygous individuals. Nevertheless, two individuals from one family were found to have a group A red cell phenotype, but when the transferase genes were analyzed at nucleotide 523 with enzymes BssHII and Kas I, both A and B transferase genes were detected. Further analysis of the transferase genes at nucleotide 700 by using restriction enzymes Alu I and Hpa II and those at nucleotide 793 by using enzyme BstNI found that both transferase genes in the two individuals were similar to the A transferase gene. CONCLUSION: An A allele of the group A glycosyltransferase was detected that had the same sequence as the B gene at nucleotide 523 but was identical to the A gene at positions 700 and 793. The identification of this variant gene makes genotyping at nucleotide 523 unreliable. However, analysis of the genes at other sites of nucleotide variation may accurately identify phenotypes. PMID- 7878718 TI - The chemical and immunoglobulin structural features necessary for reactions of quinine-dependent antibodies to neutrophils. AB - BACKGROUND: Previously described were three patients with quinine-dependent antibodies to neutrophils, platelets, and red cells who had episodic pancytopenia and renal failure. The nature of the antibody-drug-neutrophil interactions was investigated with sera from these patients. STUDY DESIGN AND METHODS: Sera from all three patients were tested against neutrophils in flow cytometry in the presence of several compounds related to quinine. IgG and Fab and F(ab')2 fragments were prepared from the serum of one patient and tested against neutrophils in flow cytometry and immunoprecipitation in the presence of quinine and related compounds. RESULTS: In flow cytometry, sera from all three patients plus quinidine reacted with neutrophils. Sera from Patients 1 and 3 reacted with neutrophils in the presence of cinchonidine (desmethoxy-quinine) and serum from Patient 3 also reacted with neutrophils in the presence of cinchonine (desmethoxy quinidine). None of the sera reacted with neutrophils in the presence of chloroquine or primaquine. Serum from Patient 3 plus quinolinic acid, a tryptophan metabolite, reacted with neutrophils, but sera from the other two patients did not. Patient 3 serum plus tryptophan or another tryptophan metabolite, quinalidic acid, did not react with neutrophils. IgG from Patient 3 serum reacted with neutrophils in flow cytometry in the presence of quinine, quinidine, cinchonidine, cinchonine, and quinolinic acid. F(ab')2 fragments plus quinine or cinchonidine also reacted with neutrophils, but Fab fragments plus quinine did not. In the presence of quinine, Patient 3 IgG immunoprecipitated the 85- and 60-kDa molecules and F(ab')2 fragments immunoprecipitated the 85-kDa molecule. Patient 3 serum plus quinidine, cinchonidine, cinchonine, and quinolinic acid immunoprecipitated the 130- and 85-kDa molecules, but not the 60 kDa molecule. CONCLUSION: Quinine-dependent neutrophil antibodies often react with neutrophils in the presence of quinidine and related compounds. These reactions were mediated by the F(ab')2 domain of IgG. PMID- 7878717 TI - The platelet-specific alloantigen PlA1 (HPA-1a): a comparison of flow cytometric immunophenotyping and genotyping using polymerase chain reaction and restriction fragment length polymorphism in a Swedish blood donor population. AB - BACKGROUND: There is an increasing interest in the development of rapid and reliable techniques for platelet alloantigen typing. STUDY DESIGN AND METHODS: By use of standardized flow cytometry and a specific human alloantiserum, 236 Swedish blood donors were immunophenotyped for the platelet-specific alloantigen, PlA1 (HPA-1a). RESULTS: Ten individuals (4.2%) had low fluorescence intensities and were considered PlA1-negative (HPA-1a-negative); all of them also demonstrated a PlA2/PlA2 (HPA-1b/1b) genotype in a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay of the underlying DNA polymorphism. The remaining population had clear positive fluorescence and was regarded as PlA1-positive (HPA-1a-positive). The fluorescence distribution histogram among PlA1-positive (HPA-1a-positive) individuals was dome-shaped, and those individuals who were homozygous for PlA1 (HPA-1a) could not be distinguished from those who were heterozygous. This finding was further substantiated by PCR-RFLP analysis of the PlA1/PlA2 (HPA-1a/1b) genotype; a heterozygous genotype was found among those having a medium fluorescence intensity as well as among those having a strong fluorescence intensity. CONCLUSION: Flow cytometry is a valuable tool for large-scale detection of PlA1 (HPA-1a). However, flow cytometry based on only one antiserum cannot distinguish between homozygous and heterozygous carriers of PlA1 (HPA-1a). For zygosity testing and when platelets are difficult to obtain, the PCR-RFLP technique is the assay of choice. PMID- 7878719 TI - The BEST Working Party of the International Society of Blood Transfusion: an international effort to improve the quality of blood components. AB - BACKGROUND: The Biomedical Excellence for Safer Transfusion (BEST) Working Party of the International Society of Blood Transfusion was formed with the aim of improving the quality and safety of blood components. An outline of the aims, working methodology, and results after the first 4 years of activity of the BEST Working Party is presented. RESULTS: Seven studies have been performed, evaluating techniques for counting residual white cells in white cell-reduced red cells, platelet quality control, and cellular harvests in blood components prepared with different methods. Areas of possible interest in the near future include stem cells, platelet crossmatching, and virus inactivation of blood components. An important BEST feature is the sharing of information gathered through collections of large sets of data from routine settings, so as to produce a reliable picture of the "real world." CONCLUSION: Such information could prove useful to those in charge of developing recommendations and guidelines. PMID- 7878720 TI - Human T-lymphotropic virus type I and type II infections and correlation with risk factors in blood donors from Sao Paulo, Brazil. AB - BACKGROUND: Little is known about the prevalence of and risk factors for human T lymphotropic virus type I and type II (HTLV-I, HTLV-II) infections in Brazil. STUDY DESIGN AND METHODS: Sera from 17,063 healthy Brazilian donors were screened by enzyme-linked immunosorbent assay for antibody to HTLV-I/II between August 1991 and July 1993. Repeatedly reactive samples were confirmed by Western blot, and discrimination between HTLV-I and HTLV-II was made by polymerase chain reaction or synthetic peptide enzyme-linked immunosorbent assay. A univariate analysis was performed on demographic and serologic data. RESULTS: HTLV-I infection was demonstrated in 83 percent of the 30 donors with reactive serologic tests (0.15% of the total tested [17,063]; 95% CI, 0.09-0.20) and HTLV-II infection in 17 percent (0.03% of the total tested [17,063]; 95% CI, 0.01-0.05). HTLV-I-positive donors were more likely than reference groups to be of Asian ethnicity (odds ratio [OR] 15.1; reference group: whites), more than 50 years old (OR 4.2; reference group: 20-29 years old), and positive for antibody to hepatitis C virus (anti-HCV) (OR 21.8) or to hepatitis B core (antigen) (anti HBc) (OR 5.7). HTLV-II showed a significant association with anti-HCV (OR 75.2) and anti-HBc (OR 21.8). Eleven of the 25 HTLV-I-positive donors were counseled. Family origin in endemic areas of Japan (n = 4), prior blood transfusion (n = 3), or sexual contact with prostitutes (n = 1) were the risk factors reported by 8 donors. In 3 white men, no risk factors could be identified. CONCLUSION: Both HTLV-I and HTLV-II occur among Brazilian blood donors. HTLV-I is associated with Asian ethnicity, greater age, and the presence of anti-HCV and anti-HBc. Three HTLV-I-positive donors had a history of blood transfusion, which emphasizes the need for HTLV-I/II screening in Brazil. PMID- 7878721 TI - Infectious disease markers in blood donors in northern Thailand. AB - BACKGROUND: A major epidemic of human immunodeficiency virus type 1 (HIV-1) infections that are primarily due to heterosexual transmission has developed in Thailand since 1988. The epidemic has been most severe in northern Thailand. The blood banks in Chiang Mai began screening donors for HIV-1 antibodies in February 1988 and for p24 antigen in April 1992. STUDY DESIGN AND METHODS: The trends of HIV-1 antibody prevalence were analyzed by type of donor (i.e., paid, replacement, and voluntary) for the period of 1988 through 1993. In addition, the prevalence of HIV-1 p24 antigen and of antibodies to syphilis, hepatitis B surface antigen, and hepatitis C virus was evaluated among blood donors at Chiang Mai University Hospital and the Thai Red Cross blood banks in Chiang Mai. RESULTS: The prevalence of HIV-1 antibodies increased from 0.84 percent in 1988 to 4.04 percent in 1991. Seropositivity was highest in paid professional donors. After discontinuation of the use of paid donors in 1993, HIV-1 antibody prevalence decreased to 3.34 percent. Antibody prevalence in replacement donors increased from 0.56 percent in 1988 to 5.82 percent in 1991. Among 44,446 donors tested, 7 (0.016%) were HIV-1 p24 antigen positive but antibody negative. CONCLUSION: The exclusion of paid donors and the use of p24 antigen testing are justified in northern Thailand. Additional strategies to exclude donors at very high risk and to attract those at low risk for infection should be developed and evaluated to increase blood transfusion safety in this and other, similar populations. PMID- 7878722 TI - Controversies in transfusion medicine. Prewarmed tests: pro-why, when, and how not if. PMID- 7878724 TI - Washed red cells: standard transfusion? PMID- 7878723 TI - Controversies in transfusion medicine. Prewarmed tests: con. PMID- 7878725 TI - Graft-versus-host disease associated with transfusions of HLA-matched, HLA homozygous platelets. PMID- 7878726 TI - Frequencies of the Jk(a-b-) phenotype in Polynesian ethnic groups. PMID- 7878727 TI - Severe hemolysis due to anti-D in a D-negative recipient of an orthotopic liver transplant. PMID- 7878728 TI - Use of external controls in transmissible-disease testing. PMID- 7878729 TI - Making connections: RNA-dependent amino acid recognition. PMID- 7878730 TI - Subclass-specific sequence motifs identified in Rab GTPases. PMID- 7878731 TI - A new family of peptidyl-prolyl isomerases. PMID- 7878732 TI - Conserved sequence motifs in bacterial and bacteriophage chaperonins. PMID- 7878733 TI - Specificity of the Alzheimer's amyloid precursor protein alpha-secretase. PMID- 7878734 TI - Invasion of the cabbage patch. PMID- 7878735 TI - Invasion of the cabbage patch. PMID- 7878736 TI - Invasion of the cabbage patch. PMID- 7878737 TI - Invasion of the cabbage patch. PMID- 7878738 TI - Regulation of Ras-mediated signalling: more than one way to skin a cat. AB - A powerful combination of genetics and biochemistry has provided details of how Ras-directed signalling interacts with and is regulated by other cellular signalling pathways. This might ultimately lead to the control of deregulated signalling by oncogenic Ras. Recently, progress has been made in understanding the regulation of Ras-mediated activation of the Raf-1-ERK2 kinase cascade through crosstalk with protein kinase C and cyclic-AMP-dependent protein kinase. PMID- 7878739 TI - The clot thickens: clues provided by thrombin structure. AB - Thrombin is the primary promoter of blood clotting; it also plays an important role in the regulation of the coagulation cascade and has been implicated in a number of other cellular processes. How can one molecule catalyse such a variety of events? The recent X-ray structure determination of human a-thrombin and related structures shows that the molecule can be divided into several functional regions that recognize different chemical moieties. By using different combinations of these elements, thrombin can interact with a variety of macromolecules with high specificity. PMID- 7878740 TI - Role of the sea urchin egg receptor for sperm in gamete interactions. AB - Embryonic development is initiated by a multi-step fertilization process involving induction of the acrosome reaction in sperm, sperm-egg binding, gamete membrane fusion and egg activation. In sea urchins, acrosome-reacted sperm interact, presumably via the sperm protein bindin, with a highly glycosylated receptor on the egg surface. This article highlights the recent advances in the molecular structure of the sea urchin sperm receptor and discusses its possible role in egg activation. PMID- 7878741 TI - Trehalose synthase: guard to the gate of glycolysis in yeast? AB - The addition of glucose to cells of the yeast Saccharomyces cerevisiae triggers a variety of regulatory phenomena. Initial glucose metabolism is required for the induction of most of them. Mutants deficient in both glucose-induced signalling and the control of initial glucose metabolism have a defect in the trehalose-6 phosphate synthase catalytic subunit of the trehalose synthase complex. This finding has raised novel questions about the control of glucose influx into glycolysis in yeast and its connection to the glucose-sensing mechanism. This dual function of the trehalose-6-phosphate synthase subunit has been found in several yeast species, suggesting that this control system might be widespread in fungi and possibly also in other organisms. PMID- 7878742 TI - Neuronal cdc2-like kinase. AB - Neurofilament proteins and the neuron-specific microtubule-associated protein tau are phosphorylated in vivo at sites conforming to the phosphorylation consensus motif of the cell-cycle-control protein kinase, p34cdc2-cyclin. Abnormalities in the phosphorylation of these proteins are associated with neurodegenerative disorders, such as amylotrophic lateral sclerosis and Alzheimer's disease. A cdc2 like kinase composed of cyclin-dependent kinase 5 (cdk5) and a brain-specific regulatory subunit is proposed to be responsible for the cdc2-like phosphorylation of these neuronal proteins. PMID- 7878743 TI - Calmodulin-binding domains: just two faced or multi-faceted? AB - The Ca(2+)-binding protein calmodulin binds to and activates several cellular enzymes in response to a rise in Ca2+ concentration. It binds certain basic amphiphilic helices within these enzymes, which also act as autoinhibitory domains. The modulation of the binding equilibrium of these helices between intramolecular (inhibition) and intermolecular (activation) sites forms a focal point for crosstalk between various signalling pathways. PMID- 7878744 TI - Wayward PCR primers. 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 the failure of PCR primers that have been kept a long time to amplify DNA. For details on how to partake in the newsgroup, see the accompanying box. PMID- 7878745 TI - Prolongation of skin allograft survival in mice following administration of ALLOTRAP. AB - Recently, Clayberger et al. demonstrated that ALLOTRAP, small synthetic peptides derived from a conserved region of the alpha 1 helix of certain HLA class I molecules, inhibited human CTL responses in vitro. In rats, ALLOTRAP 07 therapy combined with a subtherapeutic dose of cyclosporine led to the permanent acceptance of heart allografts. In the present study, the effect of ALLOTRAP on the survival of skin allografts in mice was studied. The tail skin of male C57B1/6 (H-2b) mice was grafted on the back of male CBA (H-2k) recipients. In untreated animals, the skin graft was rejected after 11.6 +/- 1.13 days (MST +/- SD). Cyclosporine administered orally for 5 days after transplantation prolonged graft survival to 13.1 +/- 2.13 days. ALLOTRAP 2702 prolonged graft survival to 16.57 +/- 2.15 days when administered orally for five days posttransplantation and to 18.86 +/- 0.38 when administered intraperitoneally until rejection. Thus, ALLOTRAP peptides derived from human MHC class I sequences, in addition to inhibiting human T cell responses in vitro, also prolong allograft survival in rats and mice. PMID- 7878746 TI - Effects of RS61443 on functional and morphological changes in chronically rejecting rat kidney allografts. AB - No immunosuppression agent is as yet available that prevents the process of chronic allograft rejection, the most critical cause of late organ allograft loss. RS61443 (mycophenolate mofetil) inhibits de novo DNA synthesis as well as diminishes expression of cell surface molecules and antibody production. As these factors seem important in the pathophysiology of the chronic phenomenon, we investigated the effects of the agent in an established model of chronic rejection of kidney allografts in a F344-to-Lewis rat strain combination. All recipients were treated for the first 10 days after engraftment with low-dose cyclosporine (1.5 mg/kg/day) to reverse an initial acute rejection episode. Since functional and morphological changes do not become manifest in this model until after 12 wk, treatment with RS61443 (15 mg/kg/day, p.o.) was either initiated at the day of grafting (Gp 1) or 8 wks thereafter (Gp 2), and continued throughout the follow-up period. Non-RS61443-treated allografted rats receiving vehicle only (Gp 3) developed progressive proteinuria after 12 wk. Peak cellular infiltration (particularly macrophages in glomeruli and perivascular areas) at 16 wk was associated with densely expressed adhesion molecules (ICAM-1 on endothelium), cytokines and growth factors (TNF-alpha and TGF-beta in glomeruli and PDGF on arterial smooth muscle cells). Interstitial fibrosis, with tubular atrophy, glomerulosclerosis, and varying degrees of intimal proliferation and luminal obliteration of vessels, progressed thereafter. In vitro binding of MNC from naive animals to chronically rejecting allografted kidneys generally confirmed the immunohistological observations, peaking at 12 wk; this binding was significantly inhibited by mAbs against specific adhesion molecules (CD11a, CD18, and ICAM-1). Serum-allospecific IgG and IgM peaked at 1-2 wk after engraftment in the control recipients, decreasing thereafter. Although IgM declined to baseline after 12 wk, low levels of allospecific IgG persisted throughout the follow-up period. In contrast, recipient treatment with RS61443 (both Gp 1 and Gp 2) allowed the allografts to function normally throughout follow-up period. Proteinuria was virtually absent, and morphological and immunohistological manifestations of the chronic process were markedly diminished. In addition, treated recipients developed no significant side effects, including leukopenia, anemia, thrombopenia, nephrotoxicity, and hepatotoxicity. It appears that this agent can safely prevent the changes of chronic rejection of kidney allografts in this rat model. PMID- 7878747 TI - Retransplantation after renal allograft loss due to noncompliance. Indications, outcome, and ethical concerns. AB - Noncompliance is increasingly recognized as a major cause of renal allograft loss, but the results of retransplantation of such patients have never been described. At our center, 52 of 3525 kidney recipients between June 1, 1963 and December 31, 1993 lost their graft due to overt noncompliance. Of these, 14 (27%) underwent retransplantation after thorough interdisciplinary evaluation. All but 1 patient had returned to dialysis before retransplantation. Of the retransplanted grafts, 2 were lost (1 technical failure, 1 chronic rejection in a compliant patient); both recipients were retransplanted once again. Currently, all retransplanted patients are alive and have a functioning graft. We conclude that for selected patients with graft loss due to noncompliance excellent results can be achieved with retransplantation. However, the issue of retransplanting previously noncompliant patients in the face of a significant donor organ shortage requires public debate. PMID- 7878748 TI - Lack of effect of pregnancy on renal allograft survival or function. AB - To determine whether pregnancy had a long-term influence on the survival or function of renal allografts, a case-control study was conducted. Patients were selected from a pool of 915 patients transplanted at the University of Cincinnati from 1967 to 1990. The pregnancy group consisted of 18 women who became pregnant 3 months to 17 years after transplantation and who elected to continue pregnancy. There were 26 nonpregnant female controls, and 23 male control renal transplant recipients. Matching criteria were cause of end-stage renal disease (ESRD), donor source, age at transplantation, calendar year of transplantation, time from transplantation to pregnancy, and serum creatinine concentration at the time corresponding to conception. Matching was performed by one investigator, who had no knowledge of long-term outcome in any of the patients. The three groups were well-matched with regard to these criteria. Male controls had higher baseline creatinine clearances than pregnancy cases or female controls. During pregnancy, serum creatinine levels fell by 20%, and creatinine clearance rose by 53%. Immediately after pregnancy, these values returned to baseline. Graft survival, with a mean posttransplant follow-up of 11-12 years, was 77.8% in the pregnancy cases, 69.2% in the female controls, and 69.6% in the male controls. By life table analysis, none of these differences was significant. Among surviving grafts, serum creatinine levels and creatinine clearances remained stable throughout the follow-up period. In this study, using well-matched male and nonpregnant female cohorts for comparison, pregnancy did not have an adverse long term effect on renal allograft function or survival. PMID- 7878749 TI - Variables affecting birthweight and graft survival in 197 pregnancies in cyclosporine-treated female kidney transplant recipients. AB - Outcomes from 197 pregnancies in 141 female kidney transplant recipients were analyzed from data collected via questionnaires, hospital records, and phone interviews. All recipients were maintained on cyclosporine (CsA) before and during pregnancy. Of the livebirths, 54% were premature (< 37 wk) and 50% were low-birthweight (LBW) (< 2500 g). The incidence of recipient drug-treated hypertension (HTN) was 56%; preeclampsia, 29%; infections and complications 22%; and rejection during pregnancy and up to 3 mo. post delivery (rej.), 11%. Graft loss within 2 years of delivery occurred in 9% of recipients (GrL < 2). No recipients reported a pregnancy after a postpregnancy graft loss. Mean serum creatinine was reported before, during, and after pregnancy. Mean cyclosporine doses were similar in recipients during and after pregnancy. Data were analyzed by logistic regression using SAS. Outcomes included prematurity, LBW, rej., and GrL < 2. In a case-controlled study comparing a recipient group with graft dysfunction during pregnancy vs. a group with good graft function, there was a trend toward lower mean prepregnancy CsA doses (in mg/kg) in the graft dysfunction group. A decline in recipient graft function during pregnancy is associated with lower newborn birthweights and lower maternal graft survival in cyclosporine treated female kidney recipients. Pregnancy-related infections and complications are associated with rejection and graft loss in this population. Close monitoring of CsA dosing and serum creatinine levels during pregnancy and immediately postpartum is recommended as CsA dosage adjustment may be required. PMID- 7878750 TI - Primary kidney tumors before and after renal transplantation. AB - Three groups of patients were reviewed. Primary carcinomas were found in donors kidneys of 47 recipients. In 30 instances a tumor was present at harvesting. When a neoplasm was removed immediately pretransplantation or early posttransplantation there were no recurrences in 14 recipients. In another two instances, a tumor was not removed or was incompletely excised pretransplantation and both recipients died of metastases. Fourteen other patients received kidneys from donors in whom the opposite kidney had a malignancy. Thirteen remained tumor free and one had allograft nephrectomy for rejection 3 months posttransplantation when a carcinoma was found. In 17 recipients an allograft neoplasm was not recognized at harvesting. In 9 it was discovered at graft nephrectomy an average of 3 months posttransplantation. In a tenth patient a hypoechogenic area, found on routine posttransplant ultrasonography, progressively increased in size and proved to be malignant. Another 7 patients developed metastases from renal carcinomas an average of 12 months posttransplantation. Preexisting carcinomas were found in 350 recipients. Seventy-one patients with incidentally discovered tumors had no recurrences no matter when nephrectomy was performed in relationship to transplantation. Of 279 patients with symptomatic renal tumors, 70 (25%) had recurrences, 63% of which occurred in patients treated < or = 2 years pretransplantation. De novo cancers were found posttransplantation in 256 recipients. Renal carcinomas were 4.6% of posttransplant cancers compared with 3% of tumors in the general population. In 222 patients their own diseased kidneys were involved, in 24 tumors occurred in the allograft, and in 10 cases the site was not stated. Development of neoplasia seemed to be related not to the immunosuppressive therapy but to the underlying cause of renal failure, especially analgesic nephropathy. A disproportionate number of carcinomas (15%) involved the renal pelvis, most likely because of prior analgesic abuse. PMID- 7878751 TI - Thromboxane synthase expression in renal transplant patients with rejection. AB - Thromboxane synthase (TS) catalyzes the formation of thromboxane (TxA2) in monocytes/macrophages, platelets, and various tissues. TxA2 is likely to play a role in graft dysfunction due to its vasoconstrictive and platelet aggregatory properties. We studied the expression of TS in 7 normal native kidneys, 29 consecutive renal allograft biopsies (performed for rising serum creatinine, n = 23, and delayed graft function, n = 6), and one transplant nephrectomy specimen with severe acute rejection. TS expression was determined by immunocytochemistry using a monoclonal antibody against human TS, Kon-7. Histologic grading of the transplant biopsy specimens was based on the Banff classification. The degree of TS staining was graded in the glomeruli, interstitium, tubules and vessels from 0 to 3+. Of 29 biopsies, 13 had chronic nephropathy (CN), 6 had acute rejection (AR) with chronic nephropathy (AR/CN), 4 had acute rejection (AR), and 6 had acute tubular necrosis (ATN). TS staining of native kidneys showed sporadic interstitial cells. The biopsy and transplant nephrectomy specimens showed significant staining, predominantly in the glomeruli and interstitium. Positively staining cells appeared to be of macrophage/monocyte lineage by morphology. The mean glomerular staining grade was significantly increased in specimens with AR (2.3 +/- 0.9) and the mean interstitial staining was increased in specimens with AR/CN (2.2 +/- 0.9). Follow-up renal function 6 months post-biopsy showed that patients with higher TS staining grades had a faster decline in graft function. In conclusion, TS expression is increased in patients with acute rejection with or without chronic nephropathy and is associated with more rapid deterioration in function. PMID- 7878752 TI - Urine cytology and urine flow cytometry in renal transplantation--a prospective double blind study. AB - Urine cytology (UC) has proved to correlate well with core and fine-needle aspiration kidney biopsies of renal allograft recipients undergoing acute rejection (AR). This study was undertaken to compare the relative usefulness of urine flow immunocytometry (UFC) (using fluorescinated antibodies anti-HLA-DR, anti-CD3 and antirenal epithelial cells) with UC in its ability to diagnose AR by analyzing 200 urine specimens during a prospective double-blind study of 40 renal transplant recipients. Clinical diagnosis was retrospectively assigned to one of the following categories: group I--AR, 15; group II--ischemic injury period (first 5 days postop.), 12; group III, 173 (including 168 stable grafts, 1 pyelonephritis and 4 cyclosporine toxicity), by investigators blinded to the urine results. Both tests were highly sensitive for the diagnosis of AR (UC = 86.6% vs. UFC = 100%; P = NS) with a specificity after the ischemic injury period of 78% by UC and 87.9% by UFC. Samples obtained during AR revealed higher levels of expression of HLA-DR as well as higher numbers of CD3-positive cells. These tests had specificity values of 95.3% and 97.6%, respectively, for the diagnosis of AR. The degree of immune activation (established by numbers of lymphocytes/lymphoblasts seen by UC) correlated with the severity of biopsy proven ARs and with response to antirejection therapy. In conclusion, both test are highly accurate in diagnosing AR. The highest specificity value was obtained when both UC and UFC were utilized together (93%). We suggest that the routine use of these tests can provide an important adjunct to the evaluation of renal transplant recipients. PMID- 7878753 TI - Analysis of rejection outcomes and implications--a report of the North American Pediatric Renal Transplant Cooperative Study. AB - For this study, we analyzed the role of rejection in graft failure in children. Rejection results were examined after 3004 pediatric renal transplants (1367 living donor, 1637 cadaver source). A total of 3453 (1298 living donor, 2155 cadaver source) rejection episodes have occurred, for rejection ratios of .95 for living donor and 1.32 for cadaver source transplants, with a constant difference of 18% points after four months, in the percentage of patients ever experiencing a rejection. Rejection results were examined by patient age (0-1 vs. 2-5 vs. 6-12 vs. > or = 13). Rejection ratios, annualized rejection frequency, time to first rejection, and mean number of rejections for patients with rejection were not elevated in the younger patients. However, for the initial rejection episode, recipients less than six years of age had significantly (P < .001) poorer outcome from the rejection episode with an increased risk of graft failure in both donor source groups. This age effect on rejection outcome is only seen with the first rejection episode and is not observed with subsequent rejection episodes. PMID- 7878755 TI - Sequential protocol biopsies in renal transplant patients. Clinico-pathological correlations using the Banff schema. AB - Twenty-five renal transplant patients on a triple immunosuppressive regimen of cyclosporine, azathioprine, and prednisone underwent protocol graft biopsies at 1, 2, 3, 6, and 12 months after transplant regardless of renal function. The histological diagnosis was made with the Banff schema. As reported previously, protocol biopsies revealed a high prevalence of subclinical rejection, as well as "borderline" inflammation, despite levels of CsA considered to be in the therapeutic range. Every biopsy was given a score for the severity of the histological changes (the Banff Score for Inflammatory Changes [BSI]), which permitted the generation of a cumulative BSI over the year of follow-up for each patient. At the end of 1 year, normal histology and excellent renal function (mean serum creatinine < 110 mumol/L) were seen only in transplant patients with the lowest cumulative BSI (P < 0.001). These results suggest that repeated inflammation in the renal allograft, even if subclinical, can lead to its dysfunction. Moreover, it would appear that, at least for the present, protocol biopsies may be required to assess adequately the effectiveness of current immunosuppressive therapies in renal transplant patients. PMID- 7878754 TI - Reduced inter- and intrasubject variability in cyclosporine pharmacokinetics in renal transplant recipients treated with a microemulsion formulation in conjunction with fasting, low-fat meals, or high-fat meals. AB - This cross-over study compared the pharmacokinetic parameters obtained from cyclosporine (CsA) concentration-time profiles after administration of the corn oil-based soft gel cap (CsA-GC) with those with the microemulsion (CsA-ME) gel cap. Neither the fasting state nor the coadministration of a low- or high-fat breakfast affected the pharmacokinetics of CsA presented in either formulation. Comparisons of the three sets of pharmacokinetic parameters--namely, after fasting or after low-fat or after high-fat diets--demonstrated the CsA-ME formulation to display greater intraindividual reproducibility of the C0 and C12 trough levels (TLs), Cmax, tmax, and area under the concentration-time curve (AUC) than the CsA-GC formulation. Although the degree of interindividual variation in AUC, Cmax and tmax after CsA-ME administration was slightly, but significantly, less than after CsA-GC administration, there was no difference between the two formulations in terms of the customarily monitored C0 or C12 TL values. CsA-ME showed higher correlation coefficients of drug exposure (AUC) with C12 than CsA-GC (0.910 versus 0.712). However, CsA-ME administration resulted in only modest improvement over CsA-GC administration in the relationships between drug dose and C0, C12, or AUC--namely, 0.645 versus 0.496, 0.611 versus 0.517, and 0.700 versus 0.501, respectively. Correlation analysis between individual timed samples and AUC determinations revealed that CsA-ME requires significantly less frequent blood monitoring for prediction of total drug exposure than does CsA-GC. Although the clinical utility of this reproducible pharmacokinetic behavior remains to be demonstrated in the de novo transplant setting, the markedly reduced intraindividual variation produced by administration of CsA-ME will likely improve the accuracy of pretransplant prediction of, and reduce the frequency of subsequent adjustments in, CsA doses. PMID- 7878756 TI - Quality of life improvements at one, two, and five years after liver transplantation. AB - We prospectively studied adult liver transplant (OLTX) recipients to evaluate the effect of OLTX on quality of life (QOL). Over an 8-year period, all adult patients undergoing OLTX at our institution were asked to complete a psychological questionnaire that probed broad facets of QOL. Patients seen for their 1, 2, and 5 or more-year post-OLTX visits were also asked to complete the form. Questions were then grouped by categories broadly highlighting self-image (SI), health perception (HP), ability to function (F), and ability to work (W). Questions ranged from demographic and occupational topics to symptom distress/frequency, activities of daily living, and the impact of health on daily life. Numerical scores were assigned to each question, and added to derive scores on SI, HP, and F. Higher scores reflect better QOL. Employment data (W) were also compared, though not amenable to scoring. A total of 573 forms were completed (210 pretransplant, 150 at 1 year, 131 at 2 years, 79 at 5 years). All posttransplant scores were significantly higher than pretransplant ones (P < or = .0001, ANOVA). Scores at posttransplant time points were not significantly different from each other. Subscores of SI and HP revealed less symptom frequency and distress following OLTX (P < or = .0003) continuing to beyond 5 years. Health limitations on activities decreased both at 1 year post-OLTX and again at 2 years (P < or = .0001) and were sustained to beyond 5 years. Fewer people were working for pay at 1 year post-compared with pre-OLTX, but pre-OLTX levels of employment had been regained by the second year, continuing to increase to beyond 5 years. OLTX leads to improved QOL by the end of the first posttransplant year, sustained through the 5th posttransplant year and beyond. Self-image, functioning ability, and perception of health status were significantly improved. Ill health interference in daily life continues to decrease as OLTX becomes more remote. Employment suffers early after OLTX, but recovers by the second post-OLTX year and continues to increase long-term. PMID- 7878757 TI - Viral and immunologic aspects of Epstein-Barr virus infection in pediatric liver transplant recipients. AB - Pediatric allograft recipients in particular are at increased risk for Epstein Barr virus (EBV)-associated disorders. Early identification and diagnosis of EBV associated disorders is critical, since disease progression can often be halted by reduction of immunosuppression. In this study we examined viral and immunologic parameters of EBV infection in the circulation of pediatric liver recipients to identify factors associated with disease. Peripheral blood DNA from pediatric liver recipients was analyzed by PCR for the EBV genes coding for the nuclear antigen 1 (EBNA-1) and the viral capsid antigen gp220. Sequences for these viral genes could be readily detected in the circulation of 36.5% of patients. Moreover, identification of the EBV genome was associated with symptomatic infection, suggesting that circulating EBV may be a useful marker of disease. Since EBV-infected B cells release the low-affinity IgE receptor (sCD23), we measured sCD23 in the circulation of pediatric liver recipients and found it to be elevated in patients with detectable virus or symptoms of infection. However, sCD23 was also elevated in cases where no EBV was detectable, suggesting that factors other than viral infection could stimulate release of sCD23. To further characterize the immune response to EBV infection, the peripheral levels of IL-4, IL-5, IL-10, and IFN-gamma were determined in pediatric liver recipients. Each of these cytokines was elevated in patients with symptoms or circulating virus compared with stable, age-matched liver recipients. IL-4, in particular, was significantly increased, indicating an important role for this cytokine in EBV infection. Together, these findings suggest that (1) monitoring circulating levels of EBV may be useful in patients at high risk and (2) cytokines that promote B cell growth and differentiation contribute to EBV associated disorders. PMID- 7878758 TI - An improved glomerular filtration rate in cardiac transplant recipients with once a-day cyclosporine dosing. AB - We tested the hypothesis that there would be a difference in the unwanted side effects of cyclosporine (CsA) when heart transplant patients received CsA once a day versus half the dose twice a day. Eight stable cardiac transplant patients (> 6 months posttransplant) were administered their dose of CsA either as a once-a day dose or half the dose b.i.d. for 21 days in a random fashion. After 21 days the patients were crossed over to the other regimen. Patients underwent inulin and PAH clearances at CsA trough on each arm of the study. Each patient collected several 24-hr urines for determination of creatinine clearance, and had ambulatory blood pressure monitoring done during each arm of the study. Serum chemistries and lipid profiles were performed at the end of each arm of the study. The CsA dose was 1.9-7.2 mg/kg/day. All patients were hypertensive and on calcium channel antagonists. Once-a-day CsA dosing resulted in a 29% decrease in trough CsA levels. A significant increase in glomerular filtration rate, as estimated by the clearance of inulin, (65.16 +/- 24.4 q. day vs. 54.62 +/- 19.0 b.i.d. (ml/min) P < .02) and a significant increase in renal plasma flow, as estimated by the clearance of PAH, occurred with once-a-day dosing when compared with b.i.d. dosing (P = .02). Creatinine clearances were not different between the 2 arms of the study and significantly overestimated glomerular filtration rates (P = .01). CsA dosing b.i.d. resulted in significantly higher nocturnal blood pressures (91.2 +/- 8.3 b.i.d. vs. 86.4 +/- 8.1 q. day, mmHg, P = .015) when compared with once-a-day dosing. A significant increase in LDL cholesterol and a significant decrease in HDL cholesterol were noted during the b.i.d. dosing arm when compared with q. day CsA dosing. We conclude that in stable heart transplant patients once-a-day CsA dosing results in better GFR and renal plasma flow, a lower nocturnal blood pressure, and an improved lipid profile when compared with dosing CsA twice a day. PMID- 7878759 TI - Bone pain that responds to calcium channel blockers. A retrospective and prospective study of transplant recipients. AB - A severe episodic bone pain syndrome of unknown cause was first described in renal transplant recipients in France and associated with the use of cyclosporine. We have retrospectively and prospectively evaluated this pain syndrome in our transplant patients. This pain is bilateral, of acute onset and episodic, primarily involving the knees and/or ankles. It usually occurs at night or with recumbency, and is often relieved with elevation or walking. Physical examination of the affected areas is unrevealing. Kidney, liver, pancreas, heart, lung and combined organ transplant recipients on cyclosporine were available from the University of Washington Transplant Services and were retrospectively evaluated by chart review (n = 351) or prospective clinical evaluation (n = 38) for evidence of this clinical syndrome. In the retrospective chart review, 19.1% of patients had episodes of bone pain. The highest prevalence occurred in renal transplant recipients (27.7%). The bone pain syndrome was documented in the charts of 14 patients who subsequently developed significant osteonecrosis. Prospectively, 21 of 22 patients with the bone pain syndrome experienced complete relief of this pain upon treatment with calcium channel blockers (95.4% response rate). The pathophysiology of this bone pain syndrome is unknown, although its response to the vasodilatory effects of calcium channel blockers suggests a vascular etiology. PMID- 7878761 TI - Increased expression of IL-4 and IL-10 and decreased expression of IL-2 and interferon-gamma in long-surviving mouse heart allografts after brief CD4 monoclonal antibody therapy. AB - In a mouse model for vascularized heart transplantation, CBA recipients of BALB/c hearts were treated with 0.25 mg of anti-CD4 (GK1.5) given intraperitoneally on the day of grafting and on days 1, 2, and 3 thereafter. This reduced splenic CD4+ cells to < 1% and all grafts survived > 100 days, compared with 8-10 days in untreated recipients. Despite recovery of the CD4+ cells after day 21, mice did not reject donor-type skin grafts at > 30 days, but rapidly rejected third-party skin, showing alloantigen-specific tolerance. The surviving heart grafts had significant mononuclear cell infiltration at time points from 7 to 100 days after transplantation. In the normal rejection process, where extensive myocyte necrosis was seen at 7 days, graft-infiltrating T cells produced IL-2 and IFN gamma. These cells responded in vitro to IL-2 and displayed donor-specific CTL activity. In contrast, cells from CD4-mAb-treated hearts did not show significant growth in IL-2 or kill donor cells in CTL assays. In these nonrejecting hearts, immunohistology showed a diffuse infiltrate of T cells and macrophages by day 3. The allograft infiltrate increased rapidly thereafter in both rejecting and nonrejecting grafts, peaking at day 6-7 in rejecting grafts, when CD4+, CD8+, and IL-2R+ cells were present, with expression of IL-2, IFN-gamma, and IL-4, but only trace levels of IL-10. From 14 to 100 days, nonrejecting allografts showed a characteristic cytokine profile of dense IL-4 and IL-10 expression on intragraft leukocytes and endothelial cells, with low levels of IL-2 and IFN-gamma. This cytokine profile, characteristic of Th2 responses, was seen in all nonrejecting grafts and was not present in rejecting grafts. Allograft tolerance can studied by examination of the functions and cytokine profile of the cells within the graft, and tolerance develops in the presence of a Th2 response within the graft. PMID- 7878760 TI - In vitro propagation and homing of liver-derived dendritic cell progenitors to lymphoid tissues of allogeneic recipients. Implications for the establishment and maintenance of donor cell chimerism following liver transplantation. AB - Dendritic cell (DC) progenitors were propagated in liquid culture from nonparenchymal cells resident in normal mouse (B10.BR; H-2k, I-E+) liver in response to granulocyte-macrophage colony stimulating factor (GM-CSF). The liver derived DC progenitors were MHC class II-/dim and did not express counter receptors for CTLA-4, a structural homologue of the T cell activation molecule CD28. Following subcutaneous or intravenous injection, these liver-derived cells migrated to T cell-dependent areas of lymph nodes and spleen of unmodified, allogeneic (B10; H-2b; I-E-) recipients, where they were identified 1-5 days, and 1 and 2 months after injection by their strong surface expression of donor MHC class II (I-Ek) and their dendritic morphology. Maximal numbers of liver-derived DC in the spleen were recorded 5 days after injection. Both clusters of strongly donor MHC class II+ cells--and (more rarely) dividing cells--could also be identified, suggesting cell replication in situ. Using the same techniques employed to generate DC progenitors from normal liver, GM-CSF-stimulated cells were propagated for 10 days from the bone marrow and spleen of nonimmunosuppressed mice sacrificed 14 days after orthotopic liver transplantation (B10;H-2b-->C3H;H-2k). Immunocytochemical staining for recipient and donor MHC class II phenotype revealed the growth both of host cells with DC characteristics, and of cells expressing donor alloantigens (I-Ab). These results are consistent with the growth, in response to GM-CSF, of donor-derived DC from progenitors seeded from the liver allograft to recipient lymphoid tissue. The functional activity of the progenitors of chimeric DC and the possible role of these cells in the establishment and maintenance of donor-specific tolerance following liver transplantation remain to be determined. PMID- 7878762 TI - Ischemic acute tubular necrosis induces an extensive local cytokine response. Evidence for induction of interferon-gamma, transforming growth factor-beta 1, granulocyte-macrophage colony-stimulating factor, interleukin-2, and interleukin 10. AB - We noted previously that ischemic acute tubular necrosis (ATN) induces local expression of MHC products in renal epithelium. The present investigations were conducted to establish the role of IFN-gamma in the regulation of MHC antigen expression in ATN and to explore the changes in cytokine and growth factor expression induced by ischemic renal injury. We produced unilateral ischemic ATN in mice by clamping the left renal pedicle. MHC class I and II steady state mRNA induction was assessed by northern blot analysis, and MHC product was quantified by the extent of binding of radiolabeled monoclonals to tissue homogenates. The steady state mRNA levels for IFN-gamma, IL-2, IL-10, and granulocyte-macrophage CSF were assessed by reverse transcriptase polymerase chain reaction and the levels for transforming growth factor-beta 1 and prepro-epidermal growth factor (ppEGF) were assessed by Northern blot analysis. In the injured kidneys, steady state mRNA levels for IFN-gamma, IL-2, IL-10, granulocyte-macrophage CSF, and transforming growth factor beta-1 were increased, whereas ppEGF mRNA was markedly decreased. The MHC expression was inhibited by treatment of mice with an anti-IFN gamma mAb (R4-6A2). Murine EGF, administered in an attempt to accelerate recovery, did not reduce the cytokine and MHC changes. These data indicate that ischemic injury, and possibly other forms of injury, triggers a complex circuit of proinflammatory cytokines. This "injury response" could be relevant to clinical renal transplants, where ATN is associated with poor graft outcome. PMID- 7878763 TI - The alloantibody network following intrathymic immunomodulation of sensitized rat recipients of cardiac allografts. AB - An intrathymic injection of allogeneic spleen cells (2 x 10(7)) prevents accelerated (< 36 hr) rejection in sensitized LEW rats, and prolongs the survival of LBNF1 cardiac allografts to about 11 days. This effect is donor-specific, x irradiation-sensitive and thymus-dependent, and it does not require adjunctive immunosuppressive therapy. We have recently shown that following intrathymic allo Ag injection, host cell proliferative responses in lymphoid organs are markedly depressed as compared with untreated sensitized recipients. Little is known about how intrathymic immunomodulation may affect host humoral alloreactivity. In this work, we studied the dynamic interplay between the humoral responses, both in the circulation and at the graft site of sensitized hosts. Intrathymic allo-Ag exposure triggered a profound change in the utilization pattern of alloreactive IgM, IgG, and IgG subclasses compared with recipients receiving syngeneic cells. Administration of allo-Ag into the thymus at the time of sensitization resulted in an earlier and significantly increased systemic production of IgM, as shown by flow cytometry. Subsequently, isotype switching to IgG occurred prematurely and resulted in elevated levels of IgG1 and IgG2a. Indeed, the addition of such allo Ab enriched serum suppressed the MLR assay in a dose-dependent manner. The binding of Ig to cardiac allografts was analyzed in eluates by flow cytometry, and by immunohistochemical staining at day 1 after transplantation. Intragraft IgM and IgG levels were consistently higher in well-functioning grafts following administration of allo-Ag, as compared with controls. IgG deposits at the graft site consisted predominantly of IgG1 and IgG2a, while significant amounts of IgG2b could only be detected in control hosts undergoing accelerated graft rejection. These data document that intrathymic injection of donor-specific allo Ag in sensitized recipients leads to profound alterations of the host humoral alloresponses, and that such elevated allo-Ab levels interfere with the Ag reactivity or alloresponsive effector cells in vitro. These results support the notion that the pattern of allo-Ab utilization is indicative of the functional status of the alloimmune response in the transplant recipient. PMID- 7878764 TI - Heat shock protein reactivity of lymphocytes isolated from heterotopic rat cardiac allografts. AB - Although it is well known that cellular rejection is mediated by alloreactive lymphocytes, several investigators, including our group, have shown that such cells are a rather small proportion of the T cell infiltrate of the alolograft. We have therefore postulated that graft-infiltrating lymphocytes must recognize other antigens. Since heat shock protein (hsp)-specific lymphocytes have been shown to participate in several autoimmune diseases and in tumor immunity, we hypothesized that hsp-reactive lymphocytes are involved with allograft rejection. This hypothesis was tested with a rat model of heterotopic MHC-incompatible cardiac allografts (ACI into Lewis), whereby graft-infiltrating lymphocytes and spleen cells were tested in vitro with different recombinant mycobacterial hsp preparations. As expected, allograft lymphocytes showed proliferative responses to irradiated spleen cells from the donor. This proliferation was markedly augmented by hsp65 (3-fold) and hsp70 (5-fold), whereas hsp10 and the protein control ovalbumin had no effect. Proliferation of allograft lymphocytes to hsp in context with syngeneic splenocytes as antigen-presenting cells (APC) was seen primarily if small quantities of IL-2 had been added to the cultures. In contrast, hsp-specific proliferation was never observed with syngraft lymphocytes, even after addition of IL-2. Spleen cells from allograft and syngraft recipients showed hsp augmentation of alloproliferation, but the magnitude was less than that with allograft lymphocytes. Kinetic studies showed that hsp-reactive lymphocytes first appeared in the allograft on day 3 posttransplant. Tacrolimus immunosuppression of transplant rejection prevented the appearance of hsp-reactive lymphocytes in allografts. Culture conditions have been established to generate hsp65- and hsp70-specific T lymphocyte lines and clones from allograft-infiltrating cells. These cultured cells exhibited hsp reactivity only in context with self-APC, and this was augmented by small amounts of IL-2. These data provide strong evidence for the involvement of hsp-reactive lymphocytes in allograft rejection. We propose the concept that during rejection tissue stress induced by alloreactive effector lymphocytes promotes the recruitment and activation of hsp-reactive lymphocytes, especially in the presence of IL-2 released into the allogeneic environment of the transplant. These hsp-reactive T cells may play a role in the immune cascade of the inflammatory process of transplant rejection. PMID- 7878765 TI - Confirmation of alternatively spliced platelet-derived growth factor-A chain and correlation with expression of PDGF receptor-alpha in human cardiac allografts. AB - PDGF is a potent mitogen for vascular smooth muscle cells (SMC) and may play an important role in the pathogenesis of cardiac allograft vasculopathy (CAV). Two isoforms of PDGF-A chain exist as a result of alternative mRNA splicing that either includes (long-form) or excludes (short-form) exon 6. Short-form PDGF-A is expressed in both resting and activated cells, while the long-form is present predominantly in activated cells. Using RT/PCR, we have found previously that long-form PDGF-A chain was expressed in human cardiac allografts but not in normal human hearts. In the experiments reported here, we studied the cellular distribution of PDGF-A chain isoforms and expression of PDGF receptor-alpha in cardiac allografts. In situ hybridization and immunohistochemistry confirmed the PCR data and demonstrated that expression of long-form PDGF-A chain was diffusely increased in cardiac allografts, predominantly in myocytes and vascular structures. Expression of PDGF receptor alpha also was induced in cardiac allografts and was not detected in any of the normal hearts. Induction of PDGF receptor alpha in cardiac allografts was associated with the presence of long form PDGF-A chain. In vitro experiments with human endothelial cells demonstrated that aFGF, IL-6, and TGF-beta, which are produced in cardiac allografts in vivo, induced expression of long-form PDGF-A chain. Expression of long-form PDGF-A chain and its receptor was markedly increased in cardiac allografts, predominantly in vascular structures and myocytes. Alterative splicing of PDGF-A chain variants may be mediated by growth factors and cytokines produced in vivo. PMID- 7878766 TI - The indirect pathway of allorecognition. The occurrence of self-restricted T cell recognition of allo-MHC peptides early in acute renal allograft rejection and its inhibition by conventional immunosuppression. AB - There is evidence that T cells can "directly" recognize intact allo-MHC molecules on the surface of allogeneic stimulator or target cells, and/or "indirectly" recognize processed allo-MHC peptides presented by self antigen-presenting cells (APCs). We and others have recently demonstrated that in vivo-primed rat CD4+ T cells recognize and proliferate to specific polymorphic amino acid sequences when presented as MHC allopeptides by self APCs. Studies on the mechanisms of indirect T cell recognition of alloantigen are now reported. First, we studied the immunogenicity of 4 synthetic polymorphic class II MHC allopeptides representing full-length sequences of the hypervariable domains of RT1.Du beta (DR or I-E like) in several responder strains: LEW (RT1(l)), ACI (RT1a), BUF (RT1b), BN (RT1n), and control syngeneic WF (RT1u) strains. Immunogenicity of the individual 25mer allopeptides varied in the different responder strains, indicating that self-restricted T cell recognition of allo-MHC peptides is determined not only by polymorphisms, but also by the responder MHC genotype. Self-restricted CD4+ T cell recognition of processed allo-MHC peptides has been shown to occur during acute skin and cardiac allograft rejection, and there is evidence that this pathway may play an important role in initiating and amplifying the immune response to allografts. T cells from LEW animals primed in vivo by WF (RT1u) vascularized renal allografts were capable of proliferating to the RT1.Du beta peptides as early as 3 days postengraftment, when presented by self APCs. We then tested the effects of various immunosuppressive drugs on self-restricted primed T cell proliferative response to an immunogenic MHC allopeptide in vitro. Methylprednisolone, cyclosporine, and FK506 inhibited the proliferative response of RT1.Du beta 2-primed LEW T cells in a dose-dependent fashion. In addition, a single injection of cyclosporine (25 mg/kg i.m.) to LEW recipients of WF renal allografts on the day of transplantation completely abolished the proliferative response of in vivo-primed T cells to RT1.Du beta 2, indicating the susceptibility of the indirect pathway of allorecognition to conventional immunosuppressive drugs. PMID- 7878768 TI - Apoptosis as a mechanism of cell death in liver allograft rejection. AB - It is generally recognized that there are two mechanisms of cell death, apoptosis and necrosis. Apoptosis--programmed cell death--is involved in numerous states of physiological cell deletion. Recent studies have demonstrated that hepatocytes, under certain conditions, undergo apoptosis. The purpose of this work was to determine if apoptotic cell death is involved in liver allograft rejection. Groups of Lewis (RT1l) rats underwent orthotopic liver transplantation (OLT) from disparate DA (RT1a) or syngeneic Lewis rats. Liver samples were harvested at 1, 2, 3, 4, and 7 days posttransplant and analyzed for apoptotic cell death. Since the characteristics of apoptosis are difficult to discern using routine hematoxylin and eosin staining, we utilized a novel method that detects the classic indicator of apoptosis, nonrandom DNA degradation. Paraffin-embedded tissue sections were end-labeled with nonradioactive dUTP and detection of apoptotic bodies accomplished by immunoassay. The incidence of apoptotic cells increased steadily over time in allografts, in contrast to syngeneic grafts. In this study apoptotic cell death paralleled standard indicators of liver allograft rejection including pathology, mononuclear cell infiltration, and increases in liver enzymes. Moreover, increased expression of TGF-beta 1 correlated with apoptosis in liver allografts, supporting the previously described role for this cytokine in hepatocyte apoptosis. Our results demonstrate, for the first time, that apoptosis may be a mechanism of cell death in liver allograft rejection. PMID- 7878767 TI - Immune status of recipients following bone marrow-augmented solid organ transplantation. AB - It has been postulated that the resident "passenger" leukocytes of hematolymphoid origin that migrate from whole organ grafts and subsequently establish systemic chimerism are essential for graft acceptance and the induction of donor-specific nonreactivity. This phenomenon was augmented by infusing 3 x 10(8) unmodified donor bone-marrow cells into 40 patients at the time of organ transplantation. Fifteen of the first 18 analyzable patients had sequential immunological evaluation over postoperative intervals of 5 to 17 months, (which included 7 kidney (two with islets), 7 liver (one with islets), and one heart recipient). The evolution of changes was compared with that in 16 kidney and liver nonmarrow controls followed for 4 to 5 months. The generic immune reactivity of peripheral blood mononuclear cells (PBMC) was determined by their proliferative responses to mitogens (PHA, ConA). Alloreactivity was measured by the recipient mixed lymphocyte reaction (MLR) to donor and HLA-mismatched third-party panel cells. Based on all 3 tests, the recipients were classified as donor-specific hyporeactive, intermediate, and responsive; patients who were globally suppressed made up a fourth category. Eight (53%) of the 15 marrow-treated recipients exhibited progressive modulation of donor-specific reactivity (3 hyporeactive and 5 intermediate) while 7 remained antidonor-responsive. In the nonmarrow controls, 2 (12.5%) of the 16 patients showed donor-specific hyporeactivity, 10 (62.5%) were reactive, and 4 (25%) studied during a CMV infection had global suppression of responsiveness to all stimuli. PMID- 7878770 TI - Obesity as a risk factor following renal transplantation. PMID- 7878769 TI - A rapid flow cytometry assay for HLA antibody detection using a pooled cell panel covering 14 serological crossreacting groups. AB - Many studies have demonstrated the usefulness of flow cytometry crossmatching (FC XM) for selection of regraft recipients, and more recently this assay has been shown to correlate with allograft survival in primary cadaveric transplant patients. The need now exists for a practical antibody screening procedure which uses the same methodology. We describe here a simple and sensitive method to screen for HLA antibodies by FC using a pool of 6 cells selected to cover the 14 serological crossreacting groups defined by Rodey. Screenings of 367 sera (255 primary transplant sera, 112 regraft sera) received for monthly antibody testing were performed by both pooled cell FC and complement-dependent cytotoxicity (CDC) assays. Forty of these sera were also FC-screened using a panel of 16 individual cells for comparison with the pooled cell FC screenings. Analysis indicated a strong correlation between the pooled FC-PRA and the individual cell panel FC-PRA (P = .0001) with mean values of 60% and 73%, respectively. Only 2 of the 40 sera screened by both FC methods resulted in PRAs that differed by > 40%. The majority (82%) of the primary patients did not exhibit HLA antibodies by CDC--however, 22% of the CDC negative patients were positive by flow cytometry. Females were more likely to be positive by FC (35%) than males (16%) (P = .0001). Similarly, black patients were more likely to have FC-demonstrable antibodies (28%) than white candidates (14%) (P = .014). The regraft patients who tested positive by either or all methods had a mean PRA for CDC, pooled FC-PRA, and individual cell FC-PRA of 40, 75, and 85, respectively. FC-PRA proved to be a more sensitive technique in both primary and regraft patients. PMID- 7878771 TI - Autonomic cardiac dysfunction in diabetic transplant recipients succumbing to sudden cardiac death. PMID- 7878772 TI - The influence of HLA donor-recipient compatibility on the recurrence of HBV and HCV hepatitis after liver transplantation. PMID- 7878773 TI - The use of spiral computed tomography in the evaluation of living donors for kidney transplantation. PMID- 7878774 TI - The fate of the failed renal transplant. PMID- 7878775 TI - Presentation of Leslie Brent, 1994 Medawar Prize Awardee. PMID- 7878776 TI - Organs should be shared on the basis of matching--con. PMID- 7878777 TI - Determination of the origin of dendritic cells in human renal grafts by demonstration of Y-body in dendritic cells. PMID- 7878778 TI - Evaluation of the Banff criteria for the histological diagnosis of rejection in renal allograft biopsies. PMID- 7878779 TI - Clinical validation and reproducibility of the Banff schema for renal allograft pathology. PMID- 7878781 TI - Clinical and renal histologic predictors of long-term outcome after OKT3 therapy for steroid-resistant rejection. PMID- 7878780 TI - Histopathological classification and clinical effects of kidney transplant rejection treated with 15-deoxyspergualin. PMID- 7878782 TI - Prognostic significance of severe interstitial edema with minimal infiltrate in renal allograft biopsies. PMID- 7878783 TI - Sequential protocol biopsies in renal transplant patients: repeated inflammation is associated with impaired graft function at 1 year. PMID- 7878784 TI - Correlation between Banff classification, acute renal rejection scores, and reversal of rejection. PMID- 7878785 TI - Living donors should be used whenever possible--pro. PMID- 7878786 TI - ABO-incompatible living kidney donor transplantation: results and immunological aspects. PMID- 7878788 TI - Effect of flow cytometry, complement-dependent cytotoxicity, and auto cross match on cadaveric renal transplant outcome. PMID- 7878787 TI - Reversible anuria associated with glomerular fibrin thrombi in ABO-incompatible renal transplants. PMID- 7878789 TI - Use of live organ donation: a necessary evil? PMID- 7878790 TI - Five year experience with protein A immunoadsorption in patients with allo/auto antibodies (anti-HLA antibodies, autoimmune bleeding disorders) and transplant patients with relapsing focal glomerular sclerosis. PMID- 7878791 TI - Primary nonfunction and preformed anti-HLA antibodies. PMID- 7878792 TI - Donor-specific transfusion in living related and unrelated donor kidney transplantation: minimal sensitization and excellent graft outcome. PMID- 7878793 TI - Successful kidney transplantation of immunized patients after desensitization with normal human polyclonal immunoglobulins. PMID- 7878794 TI - Beneficial effects of double-filtration plasmapheresis on living related donor renal transplantation in presensitized recipients. PMID- 7878795 TI - Successful renal transplantation with a positive T-cell cross match caused by IgM antibodies. PMID- 7878796 TI - The diagnostic accuracy of urine cytological analysis in the rapid assessment of acute renal allograft dysfunction. PMID- 7878797 TI - Serum C-reactive protein: a useful, economical marker of immune activation in cadaveric renal transplantation. PMID- 7878798 TI - Epidermal growth factor in urine and serum after living donor kidney transplantation. PMID- 7878800 TI - In vivo pharmacodynamics of Atgam induction immunosuppression in renal transplantation. PMID- 7878799 TI - Mizoribine as an alternative to azathioprine in triple therapy immunosuppressant regimens in cadaveric renal transplantation: two successive studies. PMID- 7878801 TI - Immunosuppressive effects of different calcium channel blockers in human kidney allografts. PMID- 7878802 TI - Treatment of acute rejection in renal graft recipients by thymoglobuline: a retrospective multicenter analysis. PMID- 7878803 TI - Biological reagents for immunosuppressants. PMID- 7878804 TI - Intraoperative high-dose anti-T-lymphocyte globulin bolus in addition to triple drug therapy improves kidney graft survival. PMID- 7878805 TI - Pentoxifylline as an adjunct to cyclosporine-based immunosuppression does not improve the outcome of renal transplantation. AB - The adjunct of PTX to the therapeutic regimen after renal transplantation had no effect on the incidence of ATN, immunologic or infectious complications, or CyA toxicity. Also, patient and graft survival was not affected. The four deaths in the study group can probably not be attributed to PTX therapy. From these data it is concluded that PTX is not able to improve the outcome of renal transplantation. PMID- 7878806 TI - Clinical use of mizoribine (Bredinin) and pharmacologic monitoring assessment in renal transplantation. PMID- 7878807 TI - Elective vs systematic corticosteroid withdrawal in renal transplant recipients receiving triple drug therapy. PMID- 7878808 TI - HLA matching determines susceptibility to harmful effects of delayed graft function in renal transplant recipients. PMID- 7878809 TI - Impact of retransplant status on delayed graft function: an analysis of paired cadaver kidneys. PMID- 7878810 TI - Excellent kidney graft survival in patients with high pretransplant serum IgA concentrations and IgA-anti-Fab autoantibody activity. PMID- 7878811 TI - Cadaver kidney transplantation with minimal delayed function: experience with perioperative strategies to enhance initial renal allograft function. PMID- 7878812 TI - Enhanced fibronectin expression is associated with the development of graft arteriosclerosis in human renal allografts. PMID- 7878813 TI - Influence of donor race on renal allograft outcome. Medical Advisory Committee, Regional Organ Bank of Illinois. PMID- 7878814 TI - Recurrent focal glomerulosclerosis in renal allografts. PMID- 7878815 TI - Parameters governing graft survival in pediatric renal transplant recipients. PMID- 7878816 TI - Outcomes of 500 pregnancies in 335 female kidney, liver, and heart transplant recipients. PMID- 7878817 TI - Urologic complications after renal transplantation: a prospective randomized trial comparing different techniques of ureteric anastomosis and the use of prophylactic ureteric stents. PMID- 7878818 TI - Should patients with renal allograft loss due to noncompliance be retransplanted? PMID- 7878819 TI - D-dimer XDP correlates with fibrinolytic shutdown in renal transplant patients treated with anti-T-cell antibodies. PMID- 7878820 TI - Role of ICAM-1 and LFA-1 in a cardiac xenograft rejection model. PMID- 7878821 TI - Cyclosporine levels in the early posttransplant period: predictive of chronic rejection in liver transplantation? PMID- 7878822 TI - Induction of transplantation tolerance by treatment with ICAM-1 antisense oligonucleotides and anti-LFA-1 monoclonal antibodies. PMID- 7878823 TI - Functional and histopathological cyclosporine A nephrotoxicity in children after organ transplantation. PMID- 7878824 TI - High-dose cyclosporine A induction therapy in liver transplant recipients with normal postoperative renal function: a prospective study. PMID- 7878826 TI - Interleukin-2 receptor antibody vs ATG for induction immunosuppression after liver transplantation: initial results of a prospective randomized trial. PMID- 7878825 TI - Donor-specific transplantation unresponsiveness in sensitized rats following treatment with a nondepleting anti-CD4 MAb is associated with selective intragraft sparing of Th2-like cells. PMID- 7878827 TI - Low incidence of chronic rejection in patients experiencing histological acute rejection without simultaneous impairment in liver function tests. PMID- 7878828 TI - Serum HLA class I soluble antigens: a marker of acute rejection following liver transplantation. PMID- 7878829 TI - Importance of ABO blood group matching in liver transplantation. PMID- 7878830 TI - Variables affecting transplantation across ABO blood groups. PMID- 7878831 TI - Evaluation of circulation status with tissue near-infrared spectroscopy in living related liver transplantation across ABO blood groups. PMID- 7878832 TI - Evaluation and morbidity of the living liver donor in pediatric liver transplantation. PMID- 7878833 TI - Donor safety in living related liver transplantation. PMID- 7878834 TI - Induction of transplantation tolerance using a nondepleting anti-CD4 MAb and donor-specific transfusion before transplantation: evidence that a critical period of time is required for the development of immunological unresponsiveness. PMID- 7878835 TI - Living related liver transplantation: a wider application. PMID- 7878836 TI - Experience from the first 30 living related liver transplant in Hamburg. PMID- 7878837 TI - Evaluation of portal hemodynamics with Doppler ultrasound in living related donor liver transplantation in children: implications for ligation of spontaneous portosystemic collateral pathways. PMID- 7878838 TI - Timing of transplantation and donor selection in living related liver transplantation for fulminant Wilson's disease. PMID- 7878839 TI - Left lateral hepatic segmentectomy in a living related donor for pediatric transplantation: the problem of segment 4. PMID- 7878840 TI - Preoperative evaluation of the living related donor in pediatric living related liver transplantation. PMID- 7878841 TI - Deleterious effect of extended cold ischemia time on the posttransplant outcome of aged livers. PMID- 7878843 TI - Liver allocation for emergency patients in France: needs and limits of a high urgency priority. PMID- 7878842 TI - HLA compatibility and liver transplant outcome: improved patient survival by HLA and crossmatching. PMID- 7878844 TI - Donor-type single MHC locus products combined with anti-CD4 MAb can induce tolerance to cardiac allografts which is dependent on active suppression. PMID- 7878845 TI - Factors relevant to the development of primary dysfunction in liver allografts. PMID- 7878846 TI - Pathologic analysis of recurrent posttransplant lymphoproliferative disorders. PMID- 7878847 TI - Prophylaxis with liposomal amphotericin B (AmBisome) prevents fungal infections in liver transplant recipients: long-term results of a randomized, placebo controlled trial. PMID- 7878848 TI - Relationship between patterns of hepatobiliary vascular supply and biliary complications in liver transplantation: an anatomical and clinical analysis. PMID- 7878849 TI - Medawar Prize Lecture: tolerance and graft-vs-host disease: two sides of the same coin. PMID- 7878850 TI - Use of anti-hepatitis C virus seropositive organs in liver transplantation. PMID- 7878851 TI - Posttransplant B, non-A non-B, and cytomegalovirus hepatitis increase the risk of developing chronic rejection after liver transplantation. PMID- 7878852 TI - Recurrent hepatitis C infection after orthotopic liver transplantation. PMID- 7878853 TI - Role of the spleen in the establishment and maintenance of anti-CD4-induced transplant nonresponsiveness. PMID- 7878854 TI - Effects of fialuridine on hepatitis B immune globulin pharmacokinetics following orthotopic liver transplant for chronic hepatitis B viral-induced cirrhosis. PMID- 7878855 TI - High incidence of posttransplant hepatitis and chronic rejection associated with hepatitis C virus infection in liver transplant recipients. PMID- 7878856 TI - Clinical course of four patients receiving the experimental antiviral agent fialuridine for the treatment of chronic hepatitis B infection. PMID- 7878857 TI - Treatment of osteoporosis after liver transplantation. PMID- 7878858 TI - Biochemical and histologic study of long-term liver transplant survivors. PMID- 7878859 TI - CD4 and CD8 monoclonal antibody therapy in the dog: strategies to induce tolerance to renal allografts. PMID- 7878860 TI - Improvement in quality of life after transplantation for recipients in the NIDDK Liver Transplantation Database. PMID- 7878861 TI - Liver transplantation halts the progress of familial amyloidotic polyneuropathy. PMID- 7878862 TI - European PH1 transplant registry report on the results of combined liver/kidney transplantation for primary hyperoxaluria 1984 to 1992. European PHI Transplantation Study Group. PMID- 7878863 TI - Changing patterns of causes of death after liver transplantation: an analysis of 41 cases in 382 patients. PMID- 7878864 TI - Impact of reduced-size liver transplantation on rejection and liver allograft outcome in the pediatric population. PMID- 7878865 TI - Is orthotopic liver transplantation for end-stage alcoholic cirrhosis justified? PMID- 7878866 TI - Hepatic resection or orthotopic liver transplant in cirrhotic patients with small hepatocellular carcinoma. PMID- 7878867 TI - Malignancy following liver transplantation: a report from the Australian Combined Liver Transplant Registry. PMID- 7878868 TI - Impact of transjugular intrahepatic portosystemic shunts on liver transplantation: a controlled analysis. NIDDK Liver Transplantation Database. PMID- 7878869 TI - A short course of cyclosporin A combined with anti-CD4 and/or anti-TCR MAb treatment induces long-term acceptance of kidney allografts in the rat. PMID- 7878870 TI - Reconstruction of bile duct using the side-to-side anastomosis in 389 orthotopic liver transplantations. PMID- 7878871 TI - TIPS: impact on liver transplantation. PMID- 7878872 TI - Liver transplantation without venovenous bypass. PMID- 7878873 TI - Liver devascularisation improves the hyperkinetic syndrome in patients with fulminant and subfulminant hepatic failure. PMID- 7878875 TI - Perioperative hyaluronic acid levels in orthotopic liver transplant recipient. PMID- 7878874 TI - Endothelin 1/2 and big-endothelin concentration in bile samples during the early postoperative period after liver transplantation. PMID- 7878876 TI - Combined liver and kidney transplantation in nephropathy associated with liver disease. PMID- 7878877 TI - Posttransplant problems requiring regrafting: an analysis of 72 patients with 96 liver retransplants. PMID- 7878878 TI - Effect of simultaneous intrathymic injection of two unrelated cellular alloantigens on rat cardiac allograft survival. PMID- 7878879 TI - Use of polymerase chain reaction to rapidly detect cytomegalovirus DNA in peripheral blood leukocytes of transplant recipients. PMID- 7878880 TI - Orthotopic vs heterotopic heart transplantation in donor/recipient size mismatch. PMID- 7878881 TI - Generation of suppressor cells maintains donor-specific tolerance after intrathymic injection of alloantigen. PMID- 7878882 TI - High-urgent repeat heart transplantation. PMID- 7878883 TI - Effects of inhaled nebulized steroids (budesonide) on acute and chronic lung function in heart-lung transplant patients. PMID- 7878884 TI - Cytokine panel predicts early rejection and therapeutic response after cardiac transplantation. PMID- 7878885 TI - Chronic rejection in heart-lung transplant recipients: the relationship between obliterative bronchiolitis and coronary artery disease. PMID- 7878886 TI - Expression of class II major histocompatibility complex antigens and lymphocyte subset immunotyping in chronic pulmonary transplant rejection. PMID- 7878887 TI - Reduced work of breathing following single lung transplantation for emphysema. PMID- 7878888 TI - The value of flow cytometric crossmatching in lung transplantation: relevance of pretransplant antibodies to lung epithelial cells. PMID- 7878889 TI - Azathioprine myelotoxicity related to elevated 6-thioguanine nucleotides in heart transplantation. PMID- 7878890 TI - Mechanisms of tolerance induction by intrathymic injection of allogeneic cells. PMID- 7878891 TI - Flow cytometry crossmatching: a method for monitoring antidonor antibodies in heart transplant recipients. PMID- 7878892 TI - Marked prolongation of incompatible class I deficient heart allografts: paradoxical effects between primarily and secondarily vascularized allografts. AB - These studies argue strongly against the widespread use of skin grafts for rejection testing. Primarily vascularized grafts of a clinically grafted organ would seem to be much more relevant to future studies. These results suggest that the elimination of either class I or class II antigens in grafts or techniques to modulate these antigens or reduce the degree of incompatibility of these antigens by tissue typing should be actively pursued for solid organ grafting in the future. PMID- 7878893 TI - Heart transplantation for end-stage valvular disease. PMID- 7878894 TI - Invasive aspergillosis after transplantation. PMID- 7878895 TI - Mechanisms of human cardiac allograft rejection: absence of co-stimulatory molecules and cell adhesion molecules on major histocompatibility complex class I/II+ human cardiac myocytes does not induce anergy. PMID- 7878897 TI - Incidence and impact of acute rejection episodes on short- and long-term graft survival in recipients of simultaneous pancreas-kidney transplantation. PMID- 7878896 TI - Triple versus quadruple induction immunosuppression in pancreas transplantation. PMID- 7878898 TI - Evidence for the role of host antigen-presenting cells in the induction of specific unresponsiveness to allografts by intrathymic inoculation of allopeptides. PMID- 7878899 TI - Simultaneous adrenal gland and kidney allotransplantation after synchronous bilateral renal cell carcinoma: a case report. PMID- 7878900 TI - Changes in cardiac function of type I diabetics following pancreas-kidney and kidney-alone transplantation. PMID- 7878901 TI - Cyclosporine blood levels predict the likelihood of rejection and toxicity after simultaneous pancreas-kidney transplantation. PMID- 7878902 TI - Diagnostic utility and correlation of duodenal and pancreas biopsy tissue in pancreaticoduodenal transplants with emphasis on therapeutic use. PMID- 7878903 TI - Impact of vascular reconstruction technique on posttransplant pancreas graft thrombosis incidence after simultaneous pancreas-kidney transplantation. PMID- 7878904 TI - Dose-dependent effect of intrathymically injected 3-mol/L KCl-extracted histocompatibility antigens to prolong heart allograft survival in rats. PMID- 7878905 TI - Early endocrine pancreas graft function and outcome after simultaneous pancreas kidney transplantation. PMID- 7878906 TI - Duct occlusion-induced vascularized islet grafts are not associated with progressive long-term dysfunction. PMID- 7878907 TI - Modification of methodology results in improvement in simultaneous kidney-islet success. PMID- 7878908 TI - Successful long-term pancreatic islet cell xenotransplantation and functional tolerance in NOD mice. AB - These findings raise a high degree of optimism concerning the potential application of this modality in higher animals. Studies are currently in process in our laboratory to apply this immunosuppressive regimen to higher animals using xenogeneic pig islets in a preclinical model that would provide the basis for future clinical trials. PMID- 7878909 TI - Intestinal transplantation: 4-year experience. PMID- 7878910 TI - Cytomegalovirus disease in intestinal transplantation. PMID- 7878911 TI - Importance of lymphoid tissue for survival of small bowel allografts. PMID- 7878912 TI - Duration of donor-specific tolerance after intrathymic administration of alloantigen. PMID- 7878914 TI - Analysis of V beta T-cell receptor repertoire of effector mechanisms in acute and chronic graft versus host disease. PMID- 7878913 TI - Cyclosporine-induced autologous graft versus host disease: assessment of cytolytic effector mechanisms and the V beta T-cell receptor repertoire. PMID- 7878915 TI - Immunological mechanisms governing tolerance to self-major histocompatibility complex antigens after bone marrow transplantation. PMID- 7878916 TI - Probability of finding a matched donor for bone marrow transplantation in a Chinese population: two year experience of an all-Chinese marrow donor registry. PMID- 7878917 TI - Use of solid phase automated sequencing to define HLA disparity between bone marrow donors and recipients. PMID- 7878918 TI - Effects of ultraviolet B irradiation on human natural killer cell and lymphokine activated killer cell activity: therapeutic potential in bone marrow transplantation and tumor immunotherapy. PMID- 7878919 TI - Abrogation of accelerated allograft rejection by intrathymic injection of donor spleen cells is associated with upregulation of donor-reactive IgM, IgG1, and IgG2A, but depression of IgG2B in the circulation and at the graft site. PMID- 7878920 TI - Bone marrow transplantation in 614 patients: twenty year experience of the Nagoya Bone Marrow Transplantation Group (NBMTG). PMID- 7878921 TI - Genotyping analysis of HLA-class II and III genes in unrelated bone marrow transplantation among Japanese. Nagoya Bone Marrow Transplantation Group and Tokai Marrow Donor Bank. PMID- 7878922 TI - Effect of posttransplant cyclosporine treatment on the development of syngeneic GVHD in recipients of UV-B irradiated bone marrow cells. PMID- 7878923 TI - Influence of lens status on graft and visual outcome in a corneal graft register. Australian Corneal Graft Registry (ACGR). PMID- 7878924 TI - Negative effect of HLA-DR matching on corneal transplant rejection. PMID- 7878925 TI - Long-term follow-up in 10 Parkinson's disease patients subjected to fetal brain grafting into a cavity in the caudate nucleus: the Clinica Puerta de Hierro experience. CPH Neural Transplantation Group. PMID- 7878926 TI - Lack of a detectable systemic humoral/cellular allogeneic response in human and nonhuman primate recipients of embryonic mesencephalic allografts for the therapy of Parkinson's disease. PMID- 7878927 TI - Diabetic polyneuropathy outcome after successful pancreas transplantation: 1 to 9 year follow up. PMID- 7878928 TI - Anti-donor antibodies in allogeneic cornea transplantation. PMID- 7878929 TI - Effect of sodium hyaluronate on diffuse epithelial keratitis after penetrating keratoplasty. PMID- 7878930 TI - Current state of composite tissue and limb allo-transplantation: do present data justify clinical application? PMID- 7878931 TI - Improved large burn therapy with reduced mortality following an associated septic challenge by early excision and skin allografting using donor-specific tolerance. AB - These studies demonstrate clearly that the creation of donor-specific tolerance in animals permits the long-term survival of incompatible skin grafts placed following a burn with early eschar excision. Furthermore, the studies demonstrate graphically that such replacement can be done without any increase in the septic mortality in these animals and strongly suggest that such a treatment would be potentially efficacious as a therapy for large body burns that could not be successfully covered with autografts. When animals were observed either in the potentially septic milieu of a large 30% body burn or in a situation of a deliberate attempt to create a septic state using the septic challenge of CLP, the placement of a full-thickness skin graft that survived was clearly beneficial to the animal in reducing mortality. In addition, the donor-specific tolerance technique described permits long-term survival of these skin grafts, which in some of the earlier laboratory studies were able to survive permanently and might well achieve permanent survival in a clinical situation. However, a prolonged graft survival of 90 to 100 days, considering the ability to develop new split thickness skin grafts providing dermal cover at 20- to 25-day intervals, would provide opportunity for a least four "croppings" of the skins. Thus, for example, a small area of remaining autograft skin of 20% in an 80% burn patient could potentially be cropped four times to achieve close to 80% coverage. Coverage would be easier and more successful in the more common burns of less than 70% of TBSA. It is of interest to us that there is virtually no well-developed literature on the use of donor-specific tolerance to aid skin graft survival. There would seem to be a reasonable rationale for considering such therapy since septic problems should not be significantly increased during induction of skin graft tolerance. Once the skin grafting has produced a significant increase in functionally covered skin, the risk of sepsis should decrease markedly. Because sepsis is currently the major factor in 75% of burn deaths, donor-specific tolerance for skins grafts appears to be eminently reasonable for future consideration. Expanded animal studies are probably necessary before clinical trials are undertaken, although skin grafting with immunosuppression has already been tried in patients. PMID- 7878932 TI - Induction of donor-specific unresponsiveness in NIH minipigs following intrathymic islet transplantation. PMID- 7878933 TI - Pilot study of mycophenolate mofetil (RS-61443) in the prevention of acute rejection following renal transplantation in Japanese patients. RS-61443 Investigation Committee--Japan. PMID- 7878934 TI - Induction of T-cell anergy by OKT3 requires cyclosporine-insensitive activation signals. PMID- 7878936 TI - A national minority organ/tissue transplant education program: the first step in the evolution of a national minority strategy and minority transplant equity in the USA. AB - 1. These successful education programs initially aimed at the AA community are being expanded into other minority groups such as Native American (Alaskan and American Indian), Hispanic (Latino), and Asian-Pacific Islander populations; and if the same modus operandus, ie, a minority-targeted message delivered by ethnically and culturally similar and sensitive messengers is used, this will have equal applicability to the majority population. MOTTEP, the first grass roots national transplant education program, while directed first to the minority population, can when presented to the majority population help all groups address the number one problem in transplantation today--the shortage of donors. 2. Active inclusion and involvement of minorities at all levels of problem resolution (resource allocation, research, and education), emphasizing community participation, education, and empowerment are the important next steps to allow for minority transplant equity in America. 3. The emergence of ASMHTP as the responsible brain trust for future minority-related efforts along with MOTTEP, a community based, empowering transplant education program, highlights the importance of a national strategy necessary for the survival of minority communities. This will enhance the interaction between minority transplant health professionals and the minority community and requires minority inclusion at all decision making levels of problem resolution within the transplant community. PMID- 7878935 TI - Sandimmun neoral pharmacokinetics: impact of the new oral formulation. PMID- 7878937 TI - Predialysis living donor renal transplantation: is it still the "gold standard" for cost, convenience, and graft survival? PMID- 7878938 TI - The Black Task Force--a community group empowered to make a difference. PMID- 7878939 TI - Successful intrathymic allografts of porcine pancreatic islets without continuous immunosuppression. PMID- 7878940 TI - Huge discrepancy between declared support of organ donation and actual rate of consent for organ retrieval. PMID- 7878941 TI - The quality of life after kidney transplantation in Japan: results from a nationwide questionnaire. PMID- 7878942 TI - Renal transplantation in Bangladesh. PMID- 7878943 TI - Transplantation in Asia: organ transplantation in Japan. PMID- 7878944 TI - Renal transplantation in Malaysia. PMID- 7878945 TI - Transplantation in Pakistan. PMID- 7878946 TI - Transplantation in Saudi Arabia. PMID- 7878947 TI - Transplantation in Singapore. PMID- 7878948 TI - Transplantation in Taiwan. PMID- 7878949 TI - Microchimerism and heart allograft acceptance. PMID- 7878950 TI - Introduction of Rupert E. Billingham. PMID- 7878951 TI - Donor microchimerism is not responsible for the maintenance of tolerance to donor alloantigens in recipients tolerant of cardiac allografts. PMID- 7878952 TI - Systemic chimerism in cadaveric kidney allograft recipients. PMID- 7878953 TI - Donor-type microchimerism after heart transplantation--a dynamic process. PMID- 7878954 TI - A gene transfer method for the study of chimerism derived from donor bone marrow in organ transplant recipients. AB - Transduction of DBMC with the neo gene did not negatively affect the viability of DBMC or the graft-prolonging effect of DBMC infusion and provided a sensitive method to monitor DBMC-derived chimerism at a microchimeric level for at least 6 months by molecular and immunohistochemical techniques. Selection of neo transduced DBMC with G418 prior to infusion will enable more uniform neo expression and will provide novel opportunities to further investigate chimerism in primates. PMID- 7878955 TI - Assessment of combined thymus and hematopoietic tissue xenografts for the induction of xenogeneic microchimerism in NOD mice. PMID- 7878956 TI - Vascularized bone marrow transplantation in rats: evidence for amplification of hematolymphoid chimerism and freedom from graft-versus-host reaction. PMID- 7878957 TI - Requirement for DR sharing in stable kidney allograft tolerance induced by donor bone marrow in rhesus monkeys. PMID- 7878958 TI - Importance of schedule of administration of adjunctive, short-term immunosuppression in ALS- and bone marrow cell-treated, skin-allografted mice. PMID- 7878959 TI - Transcript of videotape of the Rupert E. Billingham Medawar Prize ceremony. PMID- 7878960 TI - Specificity requirement of donor bone marrow cells that prolong allograft survival: implications for a veto cell mechanism of action. PMID- 7878961 TI - Intrathymic xenogeneic pancreatic islet transplantation--induction of donor specific unresponsiveness by MHC class II peptides. PMID- 7878962 TI - Retroviral vectors for long-term expression of allogeneic major histocompatibility complex transduced into syngeneic bone marrow cells. PMID- 7878963 TI - Medawar Prize Lecture--the early days of the two-way paradigm for allograft reaction. PMID- 7878964 TI - A single retroviral vector for transfer of multiple major histocompatibility complex genes: a genetic tool for transplantation tolerance. PMID- 7878965 TI - A gene transfer method for the study of chimerism derived from donor bone marrow in organ transplant recipients. AB - Transduction of DBMC with the neo gene did not negatively affect the viability of DBMC or the graft-prolonging effect of DBMC infusion and provided a sensitive method to monitor DBMC-derived chimerism at a microchimeric level for at least 6 months by molecular and immunohistochemical techniques. Selection of neo transduced DBMC with G418 prior to infusion will enable more uniform neo expression and will provide novel opportunities to further investigate chimerism in primates. PMID- 7878966 TI - Neonatally induced transplantation tolerance to primarily vascularised cardiac allografts is not donor-specific. PMID- 7878967 TI - Early neutralization of IL-4 but not of IL-10 abrogates neonatal induction of transplantation tolerance in mice. PMID- 7878968 TI - Induction of neonatal transplantation tolerance and lymphoproliferative disorders in mice: the role of F1 donor cells. PMID- 7878970 TI - Liver sinusoidal passenger lymphocytes reveal suppressive properties and prolong allograft survival. AB - Liver sinusoidal washout cells are low responders to mitogens, and suppressive in autologous PBM, and portal blood mononuclear cells, PHA supplemented, and autologous mixed lymphocyte cultures. They are less immunogenic after IV administration into allogeneic recipients than PBM, which could be measured in an in vivo allogeneic lymphocyte elimination test. The level of immunization is strain dependent. In the BN to LEW combination, they are more immunogenic than in the LEW to DA pairs. This parallels heart allograft survival times, which were longer in LEW to DA than BN to LEW combinations. PMID- 7878969 TI - Propagation of cells expressing donor phenotype (MHC class I, II and Y chromosome) from the bone marrow of murine liver allograft recipients in response to GM-CSF in vitro. PMID- 7878971 TI - Detection of blood chimerism after lung transplantation: superiority of nested as compared to standard polymerase chain reaction amplification. PMID- 7878972 TI - Graft function and rejection patterns in heart-transplanted patients with and without systemic microchimerism. PMID- 7878973 TI - Circulating donor antigen and response to donor antigen as predictors of long term lung and kidney transplant success. PMID- 7878974 TI - Weaning of immunosuppression in long-term recipients of living related renal transplants: a preliminary study. PMID- 7878975 TI - Augmentation of chimerism in whole organ recipients by simultaneous infusion of donor bone marrow cells. PMID- 7878976 TI - Long-term chimerism in liver transplantation: no evidence for immunological relevance but requirement for graft persistence. PMID- 7878977 TI - Evidence for migration of lipocytes (ITO cells) in human liver allografts with chronic dysfunction or rejection. PMID- 7878978 TI - Evidence for a possible Th2 bias in human renal transplant tolerance. PMID- 7878979 TI - Tolerance after portal venous immunization is enhanced by anti-IFN-gamma and is maintained only with persistence of antigen. PMID- 7878980 TI - Could analysis of helper T-cell precursor frequencies be used as a predictive parameter in renal transplantation? PMID- 7878981 TI - Lack of preferential Th1/Th2 cytokine gene expression patterns in both alpha/beta T-cell-tolerant and -rejecting rat cardiac allografts. PMID- 7878982 TI - Anergic T cells act as suppressor cells in vitro. PMID- 7878983 TI - Induction of specific unresponsiveness to murine cardiac allografts by intrathymic inoculation of MHC class I allopeptides. PMID- 7878984 TI - Induction of transplantation tolerance by perioperative injection of "quasi-self" chimeric class I MHC antigen combined with a short cyclosporine course. PMID- 7878985 TI - Cell interactions and cytokines in transplantation immunity. AB - Peripheral T cells usually harbor clones that can directly recognize allogeneic HLA molecules in association with hitherto undefined allogeneic peptides. However, recognition does not lead to activation of allograft immunity, unless the allogeneic cells are professional ISCs. In the absence of such cells in the graft, activation of specific alloimmunity might occur indirectly by host ISCs presenting graft-derived allogeneic peptides. Such peptides are thought to often be derived from allogeneic HLA molecules themselves. A local inflammation followed by activation of endothelial cells could facilitate the migration of immunocompetent cells into the graft parenchyma and stimulation by dendritic cells in the graft. A local inflammation is believed to be induced by ischemic damage to cells in the graft, to postoperative aseptic inflammation associated with wound healing and repair, or by ongoing local infection. Naive or virgin T cells primarily migrate to secondary lymphoid organs and specific subsets of T cells traffic selective organs such as the gut or lymph nodes. However, memory T cells extravasate to sites of local inflammation. Therefore, prior T-cell alloimmunity, which might be the result of immunity against cross-reactive self HLA restricted foreign peptides, as well as a local inflammatory reaction in the graft, caused by tissue damage or mediated by preexisting low levels of noncytotoxic antibodies, might facilitate graft rejection. PMID- 7878986 TI - Pig alpha 1, 3galactosyltransferase: sequence of a full-length cDNA clone, chromosomal localisation of the corresponding gene, and inhibition of expression in cultured pig endothelial cells. PMID- 7878987 TI - Comparative studies of the major xenoantigen gal alpha(1,3)gal in pigs and mice. PMID- 7878988 TI - Inhibition of the human antipig xenograft reaction with soluble oligosaccharides. PMID- 7878989 TI - The CD4+ effector cell in islet xenotransplantation is a macrophage and not a T lymphocyte. PMID- 7878990 TI - Macrophages and nitric oxide are involved in primary nonfunction of islet xenografts. PMID- 7878991 TI - Survival of MHC deficient mouse heterotopic cardiac allografts and xenografts. PMID- 7878992 TI - Participation of donor adhesion molecules in islet xenograft rejection. PMID- 7878993 TI - Direct and indirect recognition of pig class II antigens by human T cells. PMID- 7878994 TI - Mechanism of corneal endothelial destruction in rejecting rat corneal allografts and xenografts: a role for CD4+ cells. PMID- 7878995 TI - Role of natural killer and killer cells in concordant xenograft rejection. AB - This study was designed to test the alternative hypothesis to the T-cell cytotoxicity as a primary element in concordant xenograft rejection. Two sets of studies were done with one involving the known NK- and K-cell deficient Be mouse and another in which a normal mouse was induced with high levels (3 to 5 times normal) of LAK cell killing by a constant Osmolar Mini-Pump infusion of rIL-2. In the Be animals the CXR of skin and cardiac CXR grafts was slightly prolonged and the graft survived for a longer time than normal grafts, indicating the NK- and K cell mechanisms are operative in CXR. These studies suggest that the NK and K cells act as ancillary mechanisms in cytotoxicity in CXR. In the second portion of these studies, the increasing of LAK cell activity by infusions of rIL-2 failed to delay rejection beyond that in the Be mouse but did delay rejection beyond controls. These results suggest that the NK- and K-cell killing acts as an ancillary mechanism in CXR. Because these animals had only a slight rise in ADCC shortly after transplantation with maximum titers of 1:256 in this model, it would be presumptive to assume that cell killing was not important in CXR because many xenograft models show extraordinarily high levels of ADCC after transplantation, especially in a late transplant period. As in human allografting, the vasculitis seen with ADCC antibody could be expected to represent a significant pathology long after transplantation and this mechanism of cytotoxicity involving NK and K cells may be important in a later phase after xenografting when chronic vasculitis develops in the long surviving xenografts. Techniques for immunomodulation of the NK and K activity are now being actively pursued in our laboratory. PMID- 7878996 TI - Rejection of rat cardiac xenografts by mouse CD4 or CD8 T cells. PMID- 7878997 TI - The primacy of humoral antibody (complement-dependent cytotoxicity and antibody dependent cellular cytotoxicity) in concordant xenograft rejection. PMID- 7878998 TI - The protection from humoral rejection given by a liver xenograft is species specific and non-MHC restricted. PMID- 7878999 TI - Prevention of hyperacute xenograft rejection by intravenous immunoglobulin. PMID- 7879000 TI - White blood cells and platelets are integral to the hyperacute rejection of the pig heart by human blood. PMID- 7879001 TI - Profound pulmonary hypertension characteristic of pig lung rejection by human blood is mediated by xenoreactive antibody independent of complement. PMID- 7879002 TI - Variation in expression of porcine antigens recognized by human xenoreactive natural antibodies. PMID- 7879003 TI - Immunopathology of porcine livers perfused with blood of humans with fulminant hepatic failure. PMID- 7879004 TI - Characterisation of rat anti-guinea pig circulating xenoreactive natural antibodies and secreting cells. PMID- 7879005 TI - Natural killer cells, antibody-dependent cellular cytotoxicity, and complement synthesis by the xenograft itself play a role in xenograft rejection. PMID- 7879006 TI - High-level expression of functional human thrombomodulin in cultured porcine aortic endothelial cells. PMID- 7879007 TI - Endothelial and host mononuclear cell activation and cytokine expression during rejection of pig-to-baboon discordant xenografts. PMID- 7879008 TI - Significance of low doses of 15-deoxyspergualin in agarose-microencapsulated discordant islet xenotransplantation. PMID- 7879009 TI - Fish-to-mouse islet xenograft survival is markedly prolonged by 15 deoxyspergualin. PMID- 7879010 TI - Prolongation of islet xenograft survival with combined treatment of 15 deoxyspergualin or cyclosporine and anti-CD4 monoclonal antibody. PMID- 7879011 TI - Prolonged survival of guinea pig hearts in rats after combined antibody and complement depletion. PMID- 7879012 TI - Mechanism of leflunomide-induced prevention of xenoantibody formation and xenograft rejection in the hamster to rat heart transplantation model. PMID- 7879013 TI - Prolonged survival of cardiac xenografts between widely divergent species: bird to mammal. PMID- 7879014 TI - Vascularised mouse-to-rat heart grafts: an unexpectedly difficult model of xenotransplantation. PMID- 7879015 TI - Immunosuppressive mechanisms and action of deoxyspergualin in experimental and clinical studies. Japanese Collaborative Transplant Study Group of NKT-01. PMID- 7879016 TI - Characteristic findings of pulmonary arteriography in xenografted lung of the primates. PMID- 7879017 TI - Use of gene therapy to induce antigen-specific immunologic unresponsiveness to class I xenogeneic major histocompatibility complex antigens. PMID- 7879018 TI - Xenogeneic (rat to mouse) skin tolerance induced by monoclonal antibodies, xenogeneic cells, and cyclophosphamide. PMID- 7879019 TI - Concentration-controlled immunosuppressive regimens using cyclosporine with sirolimus or brequinar in human renal transplantation. PMID- 7879020 TI - Adenoviral-mediated gene transfer to liver xenografts results in successful expression and protein production. PMID- 7879021 TI - Simultaneous en bloc transplantation of liver, small bowel and large bowel in pigs--technical aspects. PMID- 7879022 TI - Digital image analysis of major histocompatibility complex class I and class II expression during site-specific immune suppression with topical cyclosporine. PMID- 7879023 TI - Cardiovascular consequences of immunosuppressive drug treatment: a comparative study of cyclosporine A and cyclosporine G. PMID- 7879024 TI - Cytokine expression in cardiac allografts in mice with peripheral tolerance induced by anti-ICAM-1 and anti-LFA-1 monoclonal antibodies. PMID- 7879026 TI - Monoclonal antibodies against ICAM-1 and LFA-1 (CD11A) induce specific tolerance to peripheral nerve allograft in rats. PMID- 7879025 TI - Potent immunosuppressive effect of anti-LFA-1 monoclonal antibody on islet allograft rejection. PMID- 7879027 TI - Emergence of Th2-like cells after anti-CD3 monoclonal antibody administration in mice. PMID- 7879028 TI - T-lymphocyte and cytokine-directed strategies for inhibiting skin allograft rejection in mice. PMID- 7879029 TI - Donor pretreatment with anti-T-cell receptor monoclonal antibodies prevents graft vs-host disease in brequinar-treated small bowel allograft recipients. PMID- 7879030 TI - Anti-CD4 IgG2a monoclonal antibody treatment prevents the expansion of T cells in the spleen during murine graft-vs-host disease. PMID- 7879031 TI - Prevention and reversal of renal allograft rejection by monoclonal antibody to CD45RB in the mouse model. PMID- 7879032 TI - Renal transplant morphology after long-term therapy with cyclosporine. PMID- 7879033 TI - Local immunosuppressive therapy with monoclonal anti-T-cell antibody on renal allograft survival in the rat. II. Phenotypic and functional assessment of spleen cells. PMID- 7879034 TI - Interleukin-10 eliminates anti-CD3 monoclonal antibody-induced mortality and prolongs heart allograft survival in inbred mice. PMID- 7879035 TI - Inhibition of T-cell activation by an anti-human class I MHC reactive monoclonal antibody occurs at a point distal to TCR-CD3 mediated signal transduction. PMID- 7879036 TI - Altered expression of cytokine genes by CD45RB monoclonal antibody in renal allograft rejection. PMID- 7879037 TI - Immunosuppressive 40-kd protein induced by orthotopic liver transplantation in rats. PMID- 7879038 TI - Novel immunosuppressive proteins induced in rats by liver retransplantation. PMID- 7879039 TI - Decamer peptide derived from the alpha 1 helix of the first domain of HLA-B7 01 prolongs allograft survival in rats with an inhibition of graft infiltrating cell cytotoxicity. PMID- 7879040 TI - Soluble CTLA4Ig modifies acute rejection of rat lung allografts without blocking accumulation of key cytokine transcripts. PMID- 7879041 TI - Inhibition of the alloimmune response with synthetic nonpolymorphic class II MHC peptides. PMID- 7879042 TI - Preclinical study of a recombinant soluble tumor necrosis factor receptor: effect on immune response of renal allograft recipients. PMID- 7879043 TI - Role of interferon alpha in allograft rejection. PMID- 7879044 TI - Synergistic effects of 15-deoxyspergualin with cyclosporine and the TCR-targeted monoclonal antibody R73 to induce specific unresponsiveness to skin allografts in rats. PMID- 7879046 TI - Beneficial effect of 15-deoxyspergualin on accelerated rejection in rat heart transplantation. PMID- 7879045 TI - Deoxyspergualin is a unique immunosuppressive agent with selective utility in inducing tolerance to pancreas islet xenografts. AB - Recent studies of DSG have demonstrated that this agent has a unique ability among immunosuppressive drugs to induce long-term survival and functional tolerance of discordant islet xenografts from pig to the Lewis rat. In addition, DSG was found to be nontoxic to islet cells in culture and without any inhibitory effect upon insulin secretion in contrast to azathioprine, FK 506, and CyA. The long-term functional tolerance seen with these islets appears to involve a stable block of antidonor humoral immunity, although more testing is necessary to characterize the precise state producing functional tolerance in this model. Other studies presented at this meeting demonstrate the ability of DSG and RATG immunosuppression to produce long-term discordant islet survival in the NOD mouse, which suffers from a virulent autoimmune condition that destroys transplanted islets in most NOD models shortly after transplantation, even when the islets are microencapsulated. The functional tolerance is especially difficult to achieve with a discordant xenograft and thus the ability of RATG and DSG to achieve this impressive. Long-term studies using DSG and total lymphoid irradiation suggest that RATG is not essential to long-term survival but clearly it is quite synergistic with DSG and also has the advantage of being nontoxic. In fact, all animals receiving the DSG/RATG therapy were essentially free of toxicity and no deaths were observed that could be attributed to the drug therapy. This short-term course of administration of the drugs helped achieve this lack of toxicity. The high levels of synergism of ATG in this model could be related to the numerous monoclonal reactivities seen in polyclonal ATG with demonstrated titers of 1 to 4000 or greater for a number of specificities associated with B cells and macrophages, which could well be contributing to the block of humoral antibody previously demonstrated in DSG/RATG treated animals. The DSG, however, is especially effective in synergizing an antihumoral antibody response and can be shown to result in a striking decrease in early humoral antibody production following transplantation. Overall, these studies demonstrate a high potential of this immunosuppressive therapy to promote long-term discordant islet xenograft survival and functional tolerance without chronic rejection or the islet toxicity common to the currently used immunosuppressive agent. DSG may have a wide potential utility in islet transplantation but it appears to have its strongest effect in islet xenografting. PMID- 7879047 TI - Cytokine and alloantibody networks in long-term cardiac allografts in rapamycin treated sensitized rat recipients. PMID- 7879048 TI - Rapamycin abrogates accelerated rejection in sensitized rats by selectively suppressing intragraft cell activation, adhesion/binding properties, and modulating serum alloantibody responses. PMID- 7879049 TI - Rapamycin (Sirolimus) inhibits vascular smooth muscle DNA synthesis in vitro and suppresses narrowing in arterial allografts and in balloon-injured carotid arteries: evidence that rapamycin antagonizes growth factor action on immune and nonimmune cells. PMID- 7879050 TI - Effect of rapamycin on the in vitro release of soluble interleukin-2 receptor by phytohemagglutinin, phorbol myristate acetate, and ionomycin-activated peripheral blood mononuclear cells. PMID- 7879051 TI - Inhibition of early chronic rejection in rat aortic allografts by mycophenolate mofetil (RS61443). PMID- 7879052 TI - Effect of RS61443 on chronic rejection of rat kidney allografts. PMID- 7879053 TI - Comparison of rapamycin, RS 61443, cyclosporine, and low-dose heparin as treatment for transplant vasculopathy in a rat model of chronic allograft rejection. PMID- 7879054 TI - LF 08-0299 induces tolerance after short-term treatment in a fully major histocompatibility mismatched rat cardiac allograft model. PMID- 7879055 TI - Bryostatin can induce antigen-specific nonresponsiveness in human peripheral blood T cells. PMID- 7879056 TI - Leflunomide (HWA 486) and its analog suppress T- and B-cell proliferation in vitro, acute rejection, ongoing rejection, and antidonor antibody synthesis in mouse, rat, and cynomolgus monkey transplant recipients as well as arterial intimal thickening after balloon catheter injury. PMID- 7879058 TI - New 20-epi-vitamin D3 analogs: immunosuppressive effects on skin allograft survival. PMID- 7879057 TI - Castanospermine downregulates membrane expression of adhesion molecules in heart allograft recipients. PMID- 7879059 TI - Effective suppression of brequinar sodium on accelerated allograft rejection in presensitized recipients. PMID- 7879060 TI - Induction of acute rejection by indirect recognition of donor MHC antigens. PMID- 7879061 TI - Interleukin-12: a possible cytotoxic T-lymphocyte differentiation factor in allograft recipients. PMID- 7879062 TI - HLA DR subtypes induce IL-6 and TNF-alpha production in the primary mixed lymphocyte reaction. PMID- 7879063 TI - TNF-alpha upregulates the expression of fibronectin in acutely rejecting rat cardiac allografts. PMID- 7879064 TI - Apoptosis as a mechanism of cell death in a rat model of liver allograft rejection. PMID- 7879065 TI - Role of heat shock protein immunity in allograft rejection. PMID- 7879066 TI - T-cell oligoclonality in renal allograft-infiltrating lymphocytes demonstrated by restricted T-cell receptor diversity. PMID- 7879067 TI - The use of MHC class I or class II "knock out" mice to investigate the role of these antigens in allosensitization. PMID- 7879068 TI - Restricted V beta usage by alloreactive T cells responding to specific HLA-DR alleles. PMID- 7879069 TI - The effect of antithymocyte globulin therapy on frequency and avidity of allospecific committed CTL in clinical heart transplants. PMID- 7879070 TI - Immunological monitoring in peripheral blood after heart transplantation: frequencies of T-helper cells and precursors of cytotoxic T cells with high avidity for donor antigens correlate with rejection. PMID- 7879071 TI - Concordance of mRNA expression and protein production of IL-2 and IL-4 by human heart graft-infiltrating lymphocytes. PMID- 7879072 TI - Recognition of HLA-derived peptides in transplant patients. PMID- 7879073 TI - Alloresponses in vitro and in vivo show restricted T-cell receptor V beta gene usage. AB - Our studies of V beta restriction in alloresponses have demonstrated that V beta restriction in H-2 + Mls-1a, class I and class II responses in MLC and in H-2 + Mls-1a disparate sponge matrix allografts, supporting the hypothesis that certain alloresponses in vitro and in vivo have more restricted V beta gene usage than previously thought. PMID- 7879074 TI - Allogeneic sensitization alters T-cell reactivity to extracellular matrix proteins in prospective transplant recipients. PMID- 7879076 TI - Pathogenesis and therapy of cytomegalovirus (CMV)-associated lung disease following anti-CD3 monoclonal antibody treatment in mice with persistent murine CMV in the salivary glands. PMID- 7879075 TI - Endothelial cell antigens associated with accelerated cardiac graft rejection in the rat. PMID- 7879077 TI - Facts and fancy. PMID- 7879078 TI - The role of T-helper 2 activation on transplant rejection in "low responder" rats. PMID- 7879079 TI - Characterization of cytokine expression in an animal model of acute liver allograft rejection. PMID- 7879081 TI - Mouse liver transplantation tolerance: the role of hepatocytes and nonparenchymal cells. PMID- 7879080 TI - Protective effect of alanine against graft failure of transplanted livers from fasted donor rats. PMID- 7879083 TI - Origin, occurrence, and function of passenger leukocytes in the liver. PMID- 7879084 TI - Diagnostic value of near-infrared spectroscopy for monitoring the rejection response following rat liver transplantation. PMID- 7879082 TI - The role of antibodies in liver graft-induced tolerance in mice: passive transfer of serum and effect of recipient B-cell depletion. PMID- 7879085 TI - Suppression of alloreactive T-cell activation by murine liver F4/80+ accessory cells and kinetics of intrahepatic F4/80+ cells following liver transplantation. PMID- 7879086 TI - Treatment of preservation/reperfusion injury by platelet-activating factor antagonism in the rat liver graft. PMID- 7879087 TI - Relationship between peri- and postoperative plasma concentration of endothelin-1 and liver dysfunction in rat liver transplantation. PMID- 7879088 TI - Inactivation of Kupffer cells minimizes reperfusion injury in fat-loaded livers from ethanol-treated rats. PMID- 7879089 TI - Effect of intracellular pH on reoxygenation-induced mitochondrial damage. PMID- 7879090 TI - Immunobiology of hepatic nonparenchymal cells and ex vivo perfusion of the livers with anti-class II antibody: a strategy to prevent hepatic rejection in the dog. PMID- 7879091 TI - Effects of class I major histocompatibility complex antigens on hepatic allograft survival in rats: distribution of donor cells which express class I major histocompatibility complex antigens in the recipient. PMID- 7879092 TI - The induction of immediate early genes in transplanted livers from hemorrhagic shock donor rats. PMID- 7879093 TI - Elucidation of key peptide determinants involved in an indirect T-cell allorecognition pathway of rat kidney allograft rejection. PMID- 7879094 TI - Influence of renal mass on chronic kidney allograft rejection in rats. PMID- 7879095 TI - Recombinant human dimeric tumor necrosis factor receptor (TNFR:Fc) as an immunosuppressive agent in renal allograft recipients. PMID- 7879096 TI - Morphometric analysis of rat renal allograft tolerance by computerized digital image processing. PMID- 7879097 TI - DNA nick end labeling of rat renal allografts treated with 15-deoxyspergualin (DSG). PMID- 7879098 TI - Humoral response of miniature swine tolerant to class I mismatched renal allografts. PMID- 7879099 TI - Antigen-independent events mimic characteristic changes of chronic allograft rejection. PMID- 7879100 TI - Prevention of chronic rejection of renal allografts in rats using a synthetic inhibitor of macrophage effector activation. PMID- 7879101 TI - Cytomegalovirus infection accelerates mRNA expression of several smooth muscle cell growth factors in the allograft vascular wall. PMID- 7879103 TI - Donor administration of PAF antagonist (TCV-309) enhances lung preservation. PMID- 7879102 TI - Explanation for loss of the HLA matching effect. PMID- 7879104 TI - Cytomegalovirus infection induces vascular wall inflammation and doubles arteriosclerotic changes in rat cardiac allografts. PMID- 7879105 TI - Evaluation of nitric oxide during acute rejection after heart transplantation in rats. PMID- 7879106 TI - Altered expression of smooth muscle and non-muscle myosin heavy chain isoforms in rejected hearts: a sensitive marker for acute rejection and graft coronary arteriosclerosis. PMID- 7879107 TI - Hyperlipidemia enhances chronic rejection in experimental rat model. PMID- 7879109 TI - Comparison of early postoperative hemodynamics of left and right single lung transplants after contralateral pulmonary artery ligation in the rat. PMID- 7879108 TI - Exercise capacity of rats after left or right lung transplantation followed by contralateral pulmonary artery ligation. PMID- 7879110 TI - Extrinsic nerve preservation technique for intestinal transplantation in rats. PMID- 7879111 TI - Ischemia and reperfusion injury in rat small bowel: evaluation with an ex vivo reperfusion model. PMID- 7879112 TI - Endotoxemia during small bowel transplantation in pigs. PMID- 7879113 TI - Appearance of immunoregulatory RT6+ T cells after successful pancreas transplantation in diabetic BB rats. PMID- 7879114 TI - Interleukin-10 (IL-10) prevents primary nonfunction in allogeneic islet transplantation. PMID- 7879115 TI - Administration of NG-monomethyl-L-arginine in a marginal renal subcapsular mouse islet transplant model. PMID- 7879116 TI - Engraftment and function of intrathymic pancreatic islet autografts in dogs. PMID- 7879117 TI - Proposed HLA matching scheme for improved cadaveric kidney allocation. PMID- 7879118 TI - Immunomodulation of human islets results in prolonged in vivo islet graft survival. PMID- 7879119 TI - Prolongation of islet allograft survival by anti-CD45 antibody pretreatment. PMID- 7879120 TI - Multilayer coating of islets of Langerhans: in vitro studies on a new method for immunoisolation. PMID- 7879121 TI - Protection of intrahepatic islet grafts from hyperglycemic toxicity by nicotinamide treatment. PMID- 7879123 TI - Transplantation of mismatched human fetal liver cells: tolerance induction via clonal deletion and clonal anergy. PMID- 7879122 TI - Comparison of various gels for immobilization of islets in bioartificial pancreas using a mesh-reinforced polyvinyl alcohol hydrogel tube. PMID- 7879124 TI - Purified hepatic parenchymal cells are nonimmunogenic in vitro. PMID- 7879125 TI - Hepatic transport of bile acid conjugate after hepatocyte transplantation in Eizai hyperbilirubinemic rats. PMID- 7879126 TI - Simultaneous transplantation of hepatocytes mitigates rejection of small bowel allografts in the rat. PMID- 7879127 TI - Hepatocyte transplantation in biodegradable polymer scaffolds using the Dalmatian dog model of hyperuricosuria. PMID- 7879128 TI - In vitro generation of allogeneic rather than syngeneic cytotoxic T cells for leukemia therapy. PMID- 7879129 TI - Induction of mixed bone marrow chimerism as potential therapy for autoimmune (type I) diabetes: experience in the NOD model. PMID- 7879130 TI - Genomic HLA-DR compatibility in solid organ transplantation: a retrospective analysis of 1209 cases. PMID- 7879131 TI - HLA matching and short/long-term outcome of cadaveric renal allografts: large single-centre data confirm the multicentre analyses. PMID- 7879132 TI - Impact of allocating cadaveric kidneys solely to "centers of excellence" versus by HLA matching. PMID- 7879133 TI - Impact of HLA matching, type of crossmatch, and immunosuppressive therapy on primary pediatric cadaver renal allograft survival. PMID- 7879134 TI - Repeated HLA mismatches increase the failure rate of second kidney transplants. Collaborative Transplant Study. PMID- 7879135 TI - Renal transplant graft survival results and HLA-A,B, DR mismatching. PMID- 7879136 TI - Successful renal transplantation in the presence of donor specific HLA IgM antibodies. PMID- 7879137 TI - Sensitization to HLA antigens occurs in 95% of primary renal transplant rejections. PMID- 7879138 TI - Pretransplant flow cytometry crossmatch in first cadaveric kidney transplants. PMID- 7879140 TI - DNA conformation analyses for rapid semiautomated matching of HLA class I and class II for transplantation. PMID- 7879139 TI - The liver allograft, chronic (ductopenic) rejection, and microchimerism: what can they teach us? PMID- 7879141 TI - HLA matching for local pools using fewer HLA factors. PMID- 7879142 TI - Genomic HLA-DRB1 matching further improves clinical course after renal transplantation. PMID- 7879143 TI - Polymorphism in transporter associated proteins within an antigen processing (TAP2) gene located in the HLA class II region. PMID- 7879144 TI - Allelic polymorphism in the upstream regulatory region of HLA-DRB genes: functional role of conserved consensus motifs. PMID- 7879145 TI - Analysis of rare HLA-DRB1-DQB1 haplotypes in kidney donors and recipients. PMID- 7879146 TI - Requirement for DR sharing in stable kidney allograft tolerance induced by donor bone marrow in rhesus monkeys. PMID- 7879147 TI - Polymerase chain reaction-based HLA-A genotyping and its application to matching in kidney transplantation. PMID- 7879148 TI - Xeno tissue typing using HLA-DRB1 and SLA-DRB DNA southern hybridization and xenogeneic mixed lymphocyte reactions between swine and humans. PMID- 7879149 TI - HLA DR typing by polymerase chain reaction in Terasaki trays. PMID- 7879150 TI - Importance of HLA-DRB1 amino acid residue matching between recipient and donor in cadaveric renal transplantation. PMID- 7879151 TI - Early prognosis of 263 renal allografts harvested from non-heart-beating cadavers using an in situ cooling technique. PMID- 7879152 TI - Controlled non-heart-beating donors: a potential source of extrarenal organs. PMID- 7879153 TI - Cellular and molecular biology of chronic rejection. PMID- 7879154 TI - Liver and kidney transplantation from non-heart beating donors: the Pittsburgh experience. PMID- 7879155 TI - Deleterious effect of cold preservation of rat liver on the early phase of reperfusion with special reference to tissue circulation and cytokine release. PMID- 7879156 TI - Expression of apolipoproteins A-1 and E in isolated hepatocytes preserved with the University of Wisconsin solution. PMID- 7879157 TI - Evaluation of role of leukocytes in hepatic reperfusion injury using a novel leukocyte removal system and nitro blue tetrazolium perfusion. PMID- 7879158 TI - Comparison of energy metabolism in rat liver grafts during preservation in University of Wisconsin or Euro-Collins solutions. PMID- 7879160 TI - Importance of the first minutes of reperfusion in hepatic preservation injury. PMID- 7879159 TI - Effect of preservation time on early graft function and outcome of orthotopic liver transplants. PMID- 7879161 TI - Do oxygen radicals play a role in primary dysfunction of transplanted livers following preservation in University of Wisconsin solution? PMID- 7879162 TI - Successful 48-hour preservation of the canine liver by modified simple hypothermic storage with University of Wisconsin solution. PMID- 7879164 TI - A simple method for assessment of mitochondrial viability in the liver graft. PMID- 7879163 TI - Immediate early gene expression in postischemic and transplanted livers in rats. PMID- 7879165 TI - QSA 10 (idebenone) or probucol supplementation of organ preservation solutions prevents oxygen radical-mediated injury of hepatic microsomes. PMID- 7879166 TI - Glycine in Carolina rinse solution reduces reperfusion injury, improves graft function, and increases graft survival after rat liver transplantation. PMID- 7879167 TI - Contribution of neutrophils and effect of monoclonal antibodies to adhesion molecules on ischemia and reperfusion injury in rat livers. PMID- 7879168 TI - Enhancement of glycolysis in preserved rat liver: correlation between insulin procurement and phosphofructo-1-kinase activity. PMID- 7879169 TI - Platelet activating factor antagonist has a protective effect on preservation/reperfusion injury of the graft in pig liver transplantation. PMID- 7879170 TI - Prevention of renal ischemic damage by endothelial protecting agents. PMID- 7879171 TI - Risk factors for delayed graft function in University of Wisconsin solution preserved kidneys from multiorgan donors. European Multicenter Study Group on Organ Preservation. PMID- 7879172 TI - The cytoprotective role of nitric oxide in ischemia-reperfusion injury in the rat kidney. PMID- 7879173 TI - Usefulness of continuous hypothermic perfusion preservation for cadaveric renal grafts in poor condition. PMID- 7879174 TI - Involvement of ICAM-1 expression on sinusoidal endothelial cell and neutrophil adherence in the reperfusion injury of cold-preserved livers. PMID- 7879175 TI - Donor treatment with gadolinium chloride improves survival after transplantation of cold-stored livers by reducing Kupffer cell tumor necrosis factor production in rats. PMID- 7879176 TI - Suppression of the reperfusion injury of cold-preserved livers by Kupffer cell blockade. PMID- 7879177 TI - Can anti-Mac-1 and anti-TNF monoclonal antibody protect the liver from warm ischemia-reperfusion injury in mice? PMID- 7879178 TI - Xenotransplantation: endothelial cell activation and beyond. PMID- 7879179 TI - Induction of major histocompatibility complex markers and inflammatory cytokines after ischemic injury to the kidney: lessons from interferon-gamma gene knockout mice. PMID- 7879180 TI - Beneficial effect of platelet-activating factor antagonist TCV-309 on renal ischemia-reperfusion injury. PMID- 7879181 TI - Expression of major histocompatibility complex-linked heat shock and transporter genes in rat liver after preservation. PMID- 7879182 TI - Improved small intestinal preservation with the use of lazaroid U74389G, a new free radical scavenger. PMID- 7879183 TI - Effect of luminal administration of glutamine to suppress preservation graft injury in small bowel transplants. PMID- 7879184 TI - Evaluation of viability of preserved lung by proton magnetic resonance imaging. PMID- 7879185 TI - Nafamostat mesilate rinse solution improves graft survival after rat pancreas and heart preservation. PMID- 7879186 TI - Endothelium-dependent contraction of canine coronary artery is enhanced after 24 hours of preservation with University of Wisconsin solution. PMID- 7879188 TI - The relative impact of legislative incentives on multi-organ donation rates in Europe. PMID- 7879187 TI - Hormone levels, hemodynamics, and metabolism in brain dead organ donors. PMID- 7879189 TI - Remarkable accuracy of a new cadaveric donor evaluation tool. PMID- 7879190 TI - The use of xenografts for acute hepatic failure. PMID- 7879191 TI - Cadaveric kidney allocation in the United States: a critical analysis of the point system. PMID- 7879192 TI - Optimal use for older donor kidneys: older recipients. PMID- 7879193 TI - Living-donor nephrectomy: how safe is it? PMID- 7879194 TI - Influence of HLA matching on kidney allograft survival: UNOS allocation system greatly improves the outcome. PMID- 7879195 TI - Renal transplantation in a new immunosuppressive era. PMID- 7879196 TI - FK 506: long-term study in kidney transplantation. Japanese FK 506 Study Group. PMID- 7879197 TI - Donor difficulties in Japan and Asian countries. PMID- 7879198 TI - Assessment of glomerular filtration rate after multiple administration of a new oral formulation of cyclosporine in clinically stable renal transplant patients. PMID- 7879199 TI - Variations in bioavailability of cyclosporine and relationship to clinical outcome in renal transplant subpopulations. PMID- 7879201 TI - Optimum maintenance dosage of cyclosporine and the impact on the occurrence of chronic rejection: an extensive multivariate analysis. PMID- 7879200 TI - Cyclosporine-treated renal transplant patients have only partial inhibition of calcineurin phosphatase activity. PMID- 7879202 TI - Results of a 1-year randomized controlled trial with omega-3 fatty acid fish oil in renal transplantation under triple immunosuppressive therapy. PMID- 7879203 TI - The therapeutic window of cyclosporine in Chinese recipients of renal transplantation. PMID- 7879204 TI - OKT3 prophylaxis improves long-term renal graft survival in high-risk patients as compared to cyclosporine: combined results from the prospective, randomized Belgian and US studies. PMID- 7879205 TI - Effect of anti-IL-2-receptor monoclonal antibody BT 563 in treatment of acute interstitial renal rejection. PMID- 7879208 TI - Murine OKT4A immunosuppression in cadaver donor renal allograft recipients: a cooperative pilot study (report 1). Cooperative Clinical Trials in Transplantation (CCTT) Research Group. PMID- 7879207 TI - Anti-CD4 monoclonal antibody therapy of late acute rejection in renal allograft recipients--CD4+ T cells play an essential role in the rejection process. PMID- 7879206 TI - Peripheral blood monitoring during and after rejection-prophylaxis with a monoclonal anti-interleukin-2-receptor antibody in kidney and heart transplant recipients. PMID- 7879209 TI - Multicenter comparative study of an anti-LFA-1 adhesion molecule monoclonal antibody and antithymocyte globulin in prophylaxis of acute rejection in kidney transplantation. PMID- 7879210 TI - Anti-LFA-1 adhesion molecule monoclonal antibody in prophylaxis of human kidney allograft rejection. PMID- 7879211 TI - Polymorphism of Fc receptor (Fc gamma RII) is reflected in cytokine release and adverse effects of mIgG1 anti-CD3/TCR antibody during rejection treatment after renal transplantation. PMID- 7879212 TI - Successful treatment of renal allograft rejection with a humanized antilymphocyte monoclonal antibody. PMID- 7879213 TI - Ethics in organ transplantation: the major issues. PMID- 7879214 TI - Mechanism of lymphocytopenia following administration of corticosteroids. PMID- 7879215 TI - OKT3-induced cytokine-release syndrome: occurrence beyond the second dose and association with rejection severity. PMID- 7879216 TI - Acute rejection under triple immunosuppressive therapy does not increase the risk of late first cadaveric renal allograft loss. PMID- 7879217 TI - How valid are risk factors for chronic transplant failure in renal transplant patients found in the literature with regard to our patients: results of a multivariate analysis. PMID- 7879218 TI - Can chronic vascular rejection of a renal transplant be predicted? PMID- 7879219 TI - Cytokine monitoring of infection and rejection in renal transplant recipients. PMID- 7879220 TI - Changes in urinary cytokine mRNA profile after successful therapy for acute cellular renal allograft rejection. PMID- 7879221 TI - Immunoadsorption with protein A in humoral acute rejection of kidney transplants: multicenter experience. PMID- 7879222 TI - CD3+/LFA-1 "bright" T cells represent memory-type effector cells, which, during immune activation in kidney graft recipients, are marked by increased cytokine mRNA levels. PMID- 7879223 TI - Characterization of kidney-specific peptides and their role in renal allograft rejection. PMID- 7879225 TI - Discordant graft loss from rejection of organs from the same donor in simultaneous pancreas-kidney recipients. AB - Either organ (pancreas or kidney) from a single donor in a single recipient can be discordantly lost from rejection. One can be totally rejected with the other totally normal, or the other may function within the context of chronic rejection. The pancreas is more likely to function with the kidney being rejected than vice versa. PMID- 7879224 TI - Rejection-associated abnormalities of T-cell interactions with extracellular matrix. PMID- 7879226 TI - Does suboptimal immunosuppression contribute to chronic rejection? PMID- 7879227 TI - Expression of ICAM-1 protein and ICAM-1 mRNA in human rejecting renal allografts. PMID- 7879228 TI - Th1 and Th2 cytokine gene expression in human renal allografts. PMID- 7879229 TI - Comparative flow cytometric analysis of peripheral blood, graft infiltrating and urinary sediment cells during kidney allograft rejection. PMID- 7879230 TI - The current status of the HLA controversy in clinical transplantation. PMID- 7879232 TI - Expression of the multidrug resistance gene MDR-1 in peripheral blood mononuclear cells from cyclosporine-treated renal transplant recipients rejecting their graft. PMID- 7879231 TI - Transplant glomerulopathy contribution to the decline of renal function in chronic rejection of renal transplants. PMID- 7879233 TI - Chronic renal allograft rejection can be predicted by the surface area under the serum creatinine versus time curve. PMID- 7879235 TI - Cadaveric kidneys should be allocated according to the HLA match. PMID- 7879236 TI - Immunological analysis of kidney allograft infiltrates during rejection: presence of cells coexpressing CD4 and CD8 antigens. PMID- 7879234 TI - Increased expression of growth factors during chronic rejection of human kidney allograft. PMID- 7879237 TI - Intraglomerular cathepsin B and L activity in chronic kidney allograft rejection. PMID- 7879238 TI - Treatment of acute humoral rejection in kidney transplantation with plasmapheresis. PMID- 7879239 TI - Cytomegalovirus infection associated with a decreased proliferative capacity and increased rate of apoptosis of peripheral blood lymphocytes. PMID- 7879240 TI - Circulating cytomegalovirus-infected endothelial cells after renal transplantation: possible clue to pathophysiology? PMID- 7879241 TI - Prospective longitudinal assessment of hepatitis C virus infection after renal transplantation. PMID- 7879242 TI - Treatment of chronic hepatitis C with recombinant alpha 2b interferon in kidney transplant recipients: preliminary results and side effects. PMID- 7879243 TI - Association between CMV-related graft injury and circulating cytokine-producing CD8+ memory cells. PMID- 7879244 TI - Vancomycin-resistant enterococci: an emerging pathogen in immunosuppressed transplant recipients. PMID- 7879245 TI - Renal allograft function in patients with chronic viral hepatitis B and C treated with interferon alpha. PMID- 7879246 TI - Acyclovir/cytomegalovirus immune globulin combination therapy for CMV prophylaxis in high-risk renal allograft recipients. PMID- 7879247 TI - Efficacy of cytomegalovirus prophylaxis in renal retransplantation. PMID- 7879248 TI - Strong enhancement of HLA class 1 surface expression by incomplete cytomegalovirus particles: analysis by dual-color flow cytometry using saponin. PMID- 7879249 TI - Enhanced peripheral renin activity identifies high-renin hypertension in renal transplant patients with native kidneys. PMID- 7879250 TI - Incidence and type of malignancies occurring after renal transplantation in conventionally and cyclosporine-treated recipients: analysis of a 20-year period in 1600 patients. PMID- 7879251 TI - Successful appetite suppression therapy with fenfluramine and phentermine in the obese diabetic transplant patient. PMID- 7879252 TI - Abnormal lipoprotein (a) and lipid profiles in renal allograft recipients: effects of treatment with pravastatin. PMID- 7879253 TI - Cancer risk after renal transplantation in the Norwegian transplant program. PMID- 7879254 TI - Five-year follow-up of 250 recipients of cadaveric kidney allografts from donors older than 55 years of age. PMID- 7879255 TI - Living-related renal transplantation from elderly donors (older than 66 years of age). PMID- 7879256 TI - Kidney transplantation in patients older than 70 years of age. PMID- 7879257 TI - Transplantation of kidneys from hypertensive cadaveric donors. PMID- 7879258 TI - Beneficial effects of donor-specific transfusions on long-term renal allograft function. AB - The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 163 patients by the pretransplant administration of donor specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor-recipient combinations were at least one-haplotype disparate, and 21 were two-haplotype disparate. Transient sensitization occurred in 2% and permanent sensitization in 7%. Over a 10-year period, the DST+Aza allograft survival rate is similar to the HLA-identical sibling transplants. The CMV sepsis rate was only 2%, and there were no lymphoproliferative neoplasms. The low rate of sensitization (7%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of early rejection (3%) argues for a modification of the immunologic response. PMID- 7879259 TI - Selective inactivation of cytotoxic T lymphocytes in long-term renal transplant recipients: clonal anergy as a possible mechanism underlying allograft acceptance. PMID- 7879260 TI - Presence of IgG HLA antibodies in patients with long-surviving renal allografts. PMID- 7879261 TI - Anthony and Maggie Barker. PMID- 7879262 TI - Nqutu 1965 and thereafter. PMID- 7879263 TI - The district health system: a personal perspective from Zululand. PMID- 7879264 TI - Obstetric services in a district health system in Zululand. PMID- 7879266 TI - Surgical techniques and priorities. PMID- 7879265 TI - Training general practitioners in surgical and obstetrical emergencies in Ethiopia. AB - A 6-month course for training general practitioners (GPs) in surgical emergencies was developed and piloted in Ethiopia. The course was designed after an assessment of the surgical manpower needs in Ethiopia. Seven GPs were selected by the Ministry of Health (MOH) from rural hospitals that had no surgical specialists but had operating facilities. The course consisted of 1 week of lectures followed by 11 weeks each in obstetrics/gynaecology and general surgery. The GPs trained in district hospitals under the supervision of surgical specialists. Emphasis was placed on practical experience in managing a limited number of previously identified surgical emergencies. Follow up 9 months after completion of the course showed that five of the seven GPs had completed significant numbers of life saving procedures. Complications occurred largely in advanced disease. Difficulties remain with the recognition of the GPs' training and their supervision. We conclude that GPs can be trained to provide life saving surgery in a short training programme at a modest cost, but mechanisms for ensuring ongoing support need to be established. PMID- 7879267 TI - Obstetric skills at district and sub-district hospitals. AB - A new policy for emergency obstetric care (EOC) which should be provided at district and sub-district hospitals has been adopted in Bangladesh. Therefore a survey of the obstetric skills of doctors at these institutions was performed. The current skills of the doctors was compared with their self-perceived skills when they left their medical college hospitals. Although in many cases self learning had occurred it was shown that, unless a doctor had been competent to perform a skill under indirect supervision, competency was often not reached. PMID- 7879268 TI - A simple, safe and efficient anaesthetic breathing system for universal use in rural environments. AB - A new simple, safe and efficient anaesthetic breathing system, the Humphrey ADE system, is described for universal use on adults and children. Specialist knowledge is not required as it has been designed to be easy to use. Requiring low fresh gas flows of only three to four litres per minute, the system is efficient for spontaneous, manually assisted respiration, and for controlled ventilation with an automatic ventilator. These multiple functions are dependent on only two positions of a single lever. Easy to follow instructions are permanently engraved on the main block. PMID- 7879269 TI - Surgical sets in the tropical setting. PMID- 7879270 TI - The Netherlands Working Party on Tropical Surgery. PMID- 7879271 TI - The place of amputations in the badly mutilated hand. PMID- 7879272 TI - Antipersonnel mine injuries in Somaliland: the pattern of injury. AB - Twenty patients injured by antipersonnel mines are described, with the emphasis on the relationship between the pattern of injuries, type of accident and age of the patients. Particularly severe injuries were seen in patients who travelled in the front seat of cars. Practical advice is given for the treatment. PMID- 7879273 TI - Management of small intestinal volvulus in a district hospital. AB - Primary small intestinal volvulus is one of the common causes of intestinal obstruction in various localities of the developing world. Although the general principles of management of intestinal obstruction apply to it, its diagnosis is dependent on a clinical exclusion of other causes of intestinal obstruction with overt features, and awareness of patterns of obstruction in a given locality. Moreover, in nearly all the cases early operation is recommended for a confirmation of the diagnosis and relief of the obstruction. However, lacking the necessary precautions on operation, sometimes a relief of the obstruction without a diagnostic confirmation may be the result. PMID- 7879274 TI - The management of ankle fractures. PMID- 7879275 TI - Skin cancer in Zaria, Nigeria. AB - Skin cancer from 775 patients in the savannah showed a preponderance of squamous cell carcinoma (SCC) of the leg related to neglected, poorly managed and chronic ulcers or scars from burns or injuries. SCC of the head and neck had no predisposing factor. Malignant melanoma overwhelmingly affected the feet, dermatofibrosarcoma affected the trunk and Kaposi sarcoma affected the limbs. Basal cell carcinoma (BCC) comprised only 2% of all skin cancers. The 18 albino patients had a higher frequency of both SCC and BCC mostly on the head and neck. Excisional surgery was generally effective, the wounds being closed primarily or by means of flaps and skin grafts. However, 98 patients required amputation below the knee for tibial involvement by SCC. The prognosis and health care costs of skin cancer will only be improved if burns and injuries are adequately treated. PMID- 7879276 TI - Lessons from a tropical regional hospital: a personal view of urology at KCMC, Tanzania. PMID- 7879277 TI - Is experience overseas useful for the trainee surgeon? PMID- 7879278 TI - Health care at Nqutu in 1957. PMID- 7879280 TI - [Culturing of animal and human cells, problems of cytotechnology. 4th Pushchino meeting. April 5-7, 1994. Abstracts]. PMID- 7879279 TI - Debate on the methods to improve health care. PMID- 7879282 TI - [The effect of hypothermia on certain biochemical indicators of isolated hepatocytes]. AB - The media containing nonpenetrating components (0.25 M sucrose, BSA) and antioxidant (silibor) are able for a long time to preserve at 4 degrees C a great number of liver cells. Survival of the same hepatocytes after normothermic incubation indicated a good condition of the mitochondrial system both at the stage of isolation and after hypothermic storage. Thus, by inhibiting osmotic impairment, which developed under hypothermic storage, we produced a prolongation of the time of "ageing-death" of an isolated liver cell at 4 degrees C. The addition of a drug possessing antioxidant properties was also beneficial. PMID- 7879281 TI - [Connective tissue proteins from an erosive stomach ulcer]. AB - Complex biochemical study of the connective tissue of the stomach and liver of white rats under experimental gastroduodenal ulcer and of the effect of new high protein vitaminized product "Bioctim" and ethonium has been carried out. The content of noncollagen proteins was determined from tyrosine, that of total glycoproteins from hexosamine, proteoglycans--from hexuronic acids, collagen- from oxyproline. The induced pathology is observed to result in the decrease of the concentration of tyrosine of hexosamines, hexuronic acids and oxyproline. A combined application of the above drugs takes most efficient favourable effect on the biochemical processes in the connective tissue of the stomach under given pathology. PMID- 7879283 TI - [Antioxidant and antiradical activity of various classes of antioxidants]. AB - Antiradical and antioxidative activities of classic phenolic antioxidants and blockers of Ca(2+)-channel have been studied. K2 rate constants and pI50 concentrations of tested physiologically active substances have been determined. Using the model systems of hepatic microsomal membranes lipoperoxidation it is shown that there is no distinct correlation between the antiradical and antioxidative activities of substances under investigation. These results have shown a necessity of complex evaluation of antioxidant properties of pharmacological drugs. PMID- 7879284 TI - [Free radical damage of the nuclear genetic apparatus of cells]. AB - Data which prove the important role of the lipid (as well as chromatin-bound lipids) peroxidation free radical reactions in the mechanisms of nuclear genome components damages are presented. Free radical nature of chromatin damages is proved in case of effects of ionising radiation and heavy metals ions. The role of lipid peroxidation reactions in the effects of the natural aging process, chlor- and phosphororganic chemicals intoxications is less investigated. The importance of the research of this scientific problem is discussed because of the unfavorable chemical and radiation situations. PMID- 7879285 TI - [Status of the antioxidant system at low doses and low intensities of ionizing radiation]. PMID- 7879286 TI - [A conductometric method of measuring enzymatic catalysis]. AB - Theoretical bases of the conductometric method of measurements are considered, respective formulas and equations are presented. The possibilities of application of this method for registration of the enzyme processes are shown, as well as examples of its use in conductometric classic procedure and in conductometric enzyme biosensors. Different methods of immobilization of the biological material on the surface of the transducers, schemes and methods of measurements are presented, the advantages and disadvantages of this method as compared with general biochemical methods are discussed. PMID- 7879287 TI - [Formate metabolism by lactate-producing and lactate-utilizing rumen bacteria]. AB - Physiological concentrations [< 11 mM] of formate do not violate the metabolism of S. bovis and M. elsdenii. A significant inhibition is caused by concentrations of 22 and 44 mM. In this case the process of ammonia formation in S. bovis is inhibited more pronouncedly. Peculiar effects of formate (11 mM) on LDH, FDH, aconitase, isocitrate dehydrogenase, fumarase, L-MDH and malic-enzyme have been stated. The changes show that it enhances assimilation of sugars fermented to lactate in S. bovis, in contrast to M. elsdenii, where it activates the utilization of lactic acid. During the log-phase S. bovis utilized only 11.5% of [14C] H2O2, whereas M. elsdenii uses 33.4% of it. The major amount of the label is transferred from intracellular inclusions to nucleic acids (in S. bovis- 74.7%, in M. elsdenii--87%) and then incorporated into low molecular substances (23.5 and 11.9%, respectively), the rest being incorporated into proteins and lipids. PMID- 7879289 TI - [A comparative study of the interaction between glutathione reductase and 6 phosphogluconate dehydrogenase of rat liver with certain affinity sorbents]. AB - A comparative study of the conditions of interaction of some group-specific ligands with rat hepatic 6-phosphogluconate dehydrogenase and glutathione reductase was accomplished. The influence of ionic strength and coenzyme concentration in buffer solution on the extent of enzymes binding with immobilized 2',5'-ADP and procion red HE-3B was studied according to the residual enzymatic activity after the interaction of enzyme and adsorbent. The optimal conditions have been found for enzymes binding and for their elution resulted in the effective purification of the enzymes mentioned above. Enzymatic preparations were free from the contaminating activity of each other. Dye-ligand chromatography step on red sepharose was introduced into the three step scheme of the purification of 6-phosphogluconate dehydrogenase. The final preparation of 6 phosphogluconate dehydrogenase obtained by gradient salt elution of the enzyme from the red sepharose column (0-0.15 M KCl) has the specific activity of 30-34 E/mg and shows electrophoretical homogeneity. The contribution of ionic strength and biospecific interaction of the nucleotide binding site of the enzymes during chromatography on these adsorbents is discussed. PMID- 7879288 TI - [The effect of antibiotics on staphylococcal respiratory chain enzymes]. AB - Comparative data were presented about the effect of tetracycline, chloramphenicol, erythromycin (antibiotics-inhibitors of protein synthesis) and penicillin (inhibitor of biosynthesis of cell wall components) on the enzymes of staphylococci respiratory chain. It was shown that antibiotics affected energetic metabolism of cells. It was proved by change of activity of electron transport chain enzymes--oxidases, dehydrogenases, and by change of functioning of membrane bonded ATP-ase. This effect is shown both in antibiotics addition to growing staphylococci cells and in their influence in vitro on the membrane apparatus of staphylococci cells. On the basis of these results we can suppose that the mechanism of action of these antibiotics has more complex character and side by side with protein synthesis and synthesis of cell wall it influences the activity of membrane-bonded enzymes. PMID- 7879290 TI - [The role of specific blood serum factors in disrupting insulin binding to erythrocyte cell membrane receptors]. AB - The alteration of indices of 125-I insulin binding to receptors in the reactions with human erythrocytes, with their membranes and with solubilized insulin receptors in the presence of type 2 diabetics' blood serum was demonstrated (decrease of the number of insulin binding sites and increase of the dissociation constant). Treatment of patients' erythrocytes with acetate buffer solution (0.1 M, pH 5, 150 mM sodium chloride) restored the level of specific binding of insulin to normal values. It is supposed that in insulin-independent diabetes mellitus patients' serum there are specific blocking factors which interact immediately with insulin receptors thus preventing them from hormone binding or reducing their affinity. PMID- 7879291 TI - [Features of the effect of ukrinol on the phospholipid spectrum in white rat whole blood and erythrocyte membranes in a chronic experiment]. AB - Qualitative composition and quantitative changes of phospholipids of the whole blood and membranes of white rats erythrocytes have been studied as affected by ukrinol. Regularities in the change of phylogenetically stabilized phospholipid phospholipid relations in the studied biological systems have been found under the long-term effect of ukrinol on the organism. The ways of normalizing of the disturbed phospholipid metabolism under ukrinol intoxication are discussed. PMID- 7879292 TI - [Participation of benzodiazepine receptors in the mechanism of action of nicotinamide in nerve cells]. AB - Bicucculine being introduced to rats has induced an increase of [14C]GABA capture with synaptosomes and simultaneous decrease of GABA and NAD level in the brain. The decrease of the inhibiting effect of GABA is accompanied by the increase of specific binding of [3H]flunitrazepam with benzodiazepine receptors at the expense of the increase of binding capacity from 0.33 to 0.45 g/mol per 100 mg of protein. Under these conditions the dissociation constant remains unchanged. Such an activation of benzodiazepine receptors was observed under the lack of NAD in the organism (model of PP-hypovitaminosis). Introduction of the surplus doses of nicotinamide neutralizes the convulsant effect on benzodiazepine receptors. PMID- 7879293 TI - [Features of the isoelectric distribution of human immunoglobulin G depending on the type of light chains]. AB - Physicochemical properties of immunoglobulin G of human blood serum under different states of the organism have been studied. Certain regularity of pH distribution of IgG molecules which include different kinds of light chains has been first demonstrated using the method of isoelectrical focusing in a horizontal multicell apparatus of own construction in the system of ampholines (LKB, Sweden). This distribution changes directly depend on the peculiarities of the pathological process. The increase of a share of kappa-containing molecules of serum IgG in the alkali (by isopoints) fractions for the acute period of autoimmune thyroiditis, nodular toxic goiter, insulin depending diabetes mellitus, systemic lupus erythematosus is observed. The decrease of this parameter is characteristic under diffuse toxic goiter, gastric and duodenal peptic ulcer. IgG which takes direct part in immunocomplex processes differs from serum one by its physicochemical properties. In particular, this is manifested in the distribution of separate fractions in isospectrum, in the composition with other proteins and correlation of the types of light chains in them depending on concrete pathology. PMID- 7879294 TI - [Antioxidant effect of a phospholipid complex isolated from marine organisms]. AB - Antioxidative effect of phospholipid complex from the sea organisms (preparation "Kalmofil") is observed comparatively with other phospholipid fractions of animal and plant origin. Most antioxidative action of the phospholipid complex from Mollusca (preparation "Kalmofil") on the nonenzymatic LPO reactions in vitro is established. Analogous fractions from different functional animal tissues have not such influence. Application of "Kalmofil" in vivo under experimental rat hepatitis provoked by CCl4 has a corrective effect on both nonenzymatic and Fe(2+)- and NADP.H-depending LPO reactions. This preparation decreases toxic influence of CCl4 and improves antioxidative system of rat hepatocytes. PMID- 7879295 TI - [Determination of the spatial structure of tRNA(Tyr) from bovine liver in solution by chemical modification with nitrosoethylurea]. PMID- 7879296 TI - [Surgical treatment of breast cancer--is there any progress?]. PMID- 7879297 TI - [Primary breast reconstruction after mastectomy for breast cancer]. AB - Primary breast reconstruction in connection with mastectomy is a well-established procedure. The reconstruction may be carried out by the submuscular implantation of a prosthesis, in some cases preceded by tissue expansion. In situations where there is insufficient skin--or muscle-coverage, a musculocutaneous transposition flap may be used. The aim of breast reconstruction is to prevent the psychosocial sequelae of mastectomy. From experiences with secondary reconstruction, it seems that the reconstruction especially helps correct loss of feminine identity and negative body-image. Certain investigations indicate that primary reconstruction results in a clearly reduced postoperative psychological stress, whereas the extent of social and sexual sequelae seems not to vary when compared to results of secondary reconstruction. Conditions for adjuvant treatment as well as for follow-up concerning loco-regional tumour reappearance do not seem to be affected by the reconstruction. In studies published to date, consisting of relatively small patient groups and short observation periods, numbers without relapse and overall survival are found to be equivalent to that following mastectomy without reconstruction. PMID- 7879298 TI - [Information to cancer patients prior to participation in clinical trials. Evaluation of a structured information program]. AB - Informing patients before starting of antineoplastic treatment is important due to the legal aspects of clinical trials and the anxiety and uncertainty felt by the patients. This study evaluates a structured information programme used in a clinical trial. Thirty-four women were interviewed three months after receiving information about trial, using a tape-recorded structured interview. Results showed that the information was well remembered. The patients were glad to have brought a relative to the two consultations, and the time for deliberation in between was well received. The patients viewed written information as an important source of reinformation. The information provided was positively evaluated. Open and detailed information did not undermine the doctor-patient relationship. Instead it allowed patients to understand and participate in treatment decision and helped to reduce their pre-therapy anxiety and uncertainty. The results support expanding structured information programmes to include not only those patients asked to participate in the clinical trial, but all patients beginning longlasting cancer therapy. PMID- 7879299 TI - [Alzheimer-type dementia and Down syndrome]. AB - Dementia is seen earlier and more often in patients with Down syndrome (DS) than in the general population. Patients with DS develop neuropathological changes similar to the changes seen in dementia of Alzheimer's type (DAT). The literature concerning DAT in DS is reviewed. The clinical course and differential diagnoses are discussed. Before the diagnosis of DAT is made, treatable causes of dementia should be excluded. PMID- 7879300 TI - [Active euthanasia]. AB - The growing interest in the subject of active euthanasia in connection with the debate regarding legalization of such practices in Denmark necessitates taking a definite standpoint. The difference in concept between active and passive euthanasia is stressed, and the Dutch guidelines are reviewed. The article discusses how far the patient's autonomy should go, as it regards the consideration of self-determination as being too narrow a criterion in itself. The discussion on the quality of life is included, and the consequences of the process of expulsion as a sociological concept are considered--the risk of a patient feeling guilty for being alive and therefore feeling compelled to request active euthanasia. The changed function of the physician is underlined, and it is discussed whether active euthansia will cause a breach of confidence between the physician and his patient. In connection with the debate the following tendencies in society are emphasized: lack of clarity, increasing medicalization and utilitarian priorities. PMID- 7879301 TI - [Favourable effect of olive oil in patients with non-insulin-dependent diabetes. The effect on blood pressure, blood glucose and lipid levels of a high-fat diet rich in monounsaturated fat compared with a carbohydrate-rich diet]. AB - To compare blood pressure, glucose and fat metabolism after a high-fat diet rich in monounsaturated fat reduced day time systolic (131 +/- 3 vs. 137 +/- 3 mmHg, p < 0.04) and 24-hour systolic blood pressure (126 +/- 8 vs. 130 +/- 10 mmHg, p < 0.03) as well as day time diastolic (78 +/- 2 vs. 84 +/- 52 mmHg, p < 0.02) and diurnal diastolic blood pressure (75 +/- 6 vs. 78 +/- 5 mmHg, p < 0.03) as compared with the high-carbohydrate diet. Evidence of improved glucose tolerance on the high-monounsaturated diet compared with the high-carbohydrate diet were found with lower fasting blood glucose (6.1 +/- 0.3 vs. 6.8 +/- 0.5 mM, p < 0.05), lower average blood glucose levels (7.4 +/- 0.5 vs. 8.2 +/- 0.6 mmol/l, p < 0.01) and peak blood glucose responses (9.9 +/- 0.6 vs. 11.3 +/- 0.7 mmol/l, p < 0.02). Similar levels of fasting triglyceride, total cholesterol, LDL- and HDL cholesterol were found after the two diets. PMID- 7879302 TI - [Ambulatory coronary arteriography]. AB - Based upon hospital files and a questionnaire we assessed the patient safety of and the patient attitude towards outpatient coronary angiography (CAG). A total of 115 consecutive patients were included in the study. Thirty two of the patients (28%) were admitted following the angiography, while 83 (72%) were discharged to the home as planned. Of those de facto ambulatory patients one (1%) was readmitted because of a groin haematoma. Of those who returned the questionnaire, 93% of the patients admitted and 97% of the de facto ambulatory patients were satisfied with the level of information, and 76% and 99%, respectively, would prefer out-patient CAG to CAG during admission. We conclude that out-patient CAG can be performed with a very low risk and is well accepted by the patients. PMID- 7879303 TI - [The clinical consequence of blood culture results]. AB - The effect of blood culture results on patient management in a department of internal medicine was analyzed retrospectively. In a series of 300 patients 538 blood cultures were taken. Fifty-four (10%) of blood cultures from 44 of the 300 patients were positive, but in 16 patients cultures yielded organisms considered to be contaminants. Only 28 (9.3%) patients' cultures showed growth of clinically significant pathogenic bacteria. Antimicrobial chemotherapy was instituted in 234 (78%) patients before culture results were available. For only 21 (7%) patients did the result of the blood culture have any therapeutic consequences. The high frequency and lack of impact of negative blood cultures demands a more appropriate protocol for blood culturing, and guidelines are suggested. PMID- 7879304 TI - [Frequency of self-reported alcohol influence in injured bicycle riders]. AB - The aim of the study was to determine the frequency of self reported alcohol influence in injured bicyclists. The study was based upon a combination of data from a questionnaire and recordings from the emergency room. Eighteen percent of cyclists 15 years of age or older treated at the emergency room reported themselves influenced by alcohol at the time of accident. The highest injury rate in patients riding under influence was found in the age group 20-29 years, and the proportion of injured cyclists riding under influence was four times higher in males than in females. The lesions sustained by alcohol influenced bicyclists were not more severe than those of the not influenced injured bicyclists. PMID- 7879305 TI - [Acute pulmonary edema during general anesthesia in a young woman treated with epirubicin]. AB - The use of the anthracycline doxorubicin is restricted by its cardiac toxicity. Another anthracycline, epirubicin, is probably less cardiotoxic. A case is reported, where a 30 year-old woman with breast cancer, treated with epirubicin, developed pulmonary oedema during surgery and anaesthesia. The patient had no previous cardio-pulmonary disorders, and had only received 10% of the usual maximum dose of epirubicin. The different clinical presentations of anthracycline induced cardiac toxicity are described. PMID- 7879306 TI - [Atlanto-axial rotation-fixation in a child with clavicular fracture]. AB - A case of an eight-year-old boy who had sustained both a fractured clavicle and rotatory atlanto-axial fixation is described. The last diagnosis was missed for four and a half months. The diagnosis was made in combination with cineroentgenography and computed tomography scanning. Conservative treatment with external traction was first attempted, after which the patient was operated twice with posterior fusion between C-1 and C-2. At six month follow-up the child was without pain, had neutral head holding and about two-thirds of normal rotation. PMID- 7879307 TI - [Azoospermia in 2 body-builders after taking anabolic steroids]. AB - During investigations for infertility azoospermia was diagnosed in two men who were concomitantly using anabolic steroids for body-building. Following cessation of anabolic steroid use the semen quality was normalized. Suppression of spermatogenesis during treatment with testosterone and derivatives hereof is wellknown. Usage of anabolic steroids should be remembered as a cause of oligo- and azoospermia and asked about in cases of sperm counts approaching or at zero. PMID- 7879308 TI - [Understanding statistics?]. PMID- 7879309 TI - [Neuromuscular blockade. Dosage of nondepolarizing agents to risk-group patients]. PMID- 7879310 TI - The Sayre equation in electron crystallography. AB - The Sayre equation was evaluated as a technique for phase refinement in electron crystallography. Atomic-resolution electron diffraction data from copper perchlorophthalocyanine were assigned phase values from the Fourier transforms of various experimental electron micrographs, including one at 2.3 A, containing errors due to lens astigmatism. In each case, an atomic-resolution structure could be found after Fourier refinement. In addition, it was possible to begin with a basis set derived from symbolic addition for phase extension. Such a source of phases was also found to be useful for extending zonal electron diffraction sets from six polymer crystals, even though there was considerable overlap of atomic positions in the projection down the chain axes. Other tests of the Sayre equation were made with zonal protein data sets (bacteriorhodopsin, halorhodopsin) to evaluate what difficulties are to be expected when direct phasing techniques are to be used in macromolecular electron crystallography. Comparison to known values indicated that the low-resolution range (e.g. to 6 A) was reasonably stable for phase extension from a 10-15 A resolution image. Only when a minimum in average intensity was approached (near 5 A) did the direct extension encounter serious difficulties. If this minimum was treated as a "phase node" to generate two possible solutions, a model more similar to the true phase set was found. In general, this rather simple convolutional technique for phase extension seems to be particularly suitable for a variety of electron crystallographic applications. PMID- 7879311 TI - Proposal of alignment-independent classification of electron microscopic images with helical symmetry and its application to reconstituted thin filaments os skeletal muscle. AB - A new method to classify noisy images of filaments with helical symmetry was developed and applied to cryo-electron microscopic images of skeletal muscle thin filaments. In this method, images are transformed to minimum data sets which are independent of the relative view parameters, such as rotation of a three dimensional object around the axis of helical symmetry, translation along an axis and operation to make a filament upside down, and classified by a principal component analysis. By this method, atypical data can be identified without aligning procedures, and small structural changes and polymorphic variation are expected to be detected objectively. PMID- 7879312 TI - Renal haemodynamics and prostaglandin synthesis in partial unilateral ureteric obstruction. AB - Haemodynamic changes in partial unilateral ureteric obstruction (PUUO) may be related to altered prostaglandin synthesis. In 12 dogs the left ureter was partially obstructed for 5 weeks. In six dogs the ureter was reimplanted into the bladder and to investigate the effect of this procedure on the contralateral side the other six animals underwent ipsilateral nephroureterectomy. Renal blood flow (RBF) was measured by the distribution of radiolabelled microspheres. Changes in urinary prostaglandin (PG) concentrations were validated by renin activity using angiotensin I. Reduced left RBF during obstruction was associated with increased thromboxane A2 synthesis (P < 0.01). Increased RBF to the non-obstructed side was associated with elevated PGE2 formation (P < 0.05). Elevated angiotensin I levels (P < 0.01) corresponded to maximal increases in PG synthesis. Reimplantation of the obstructed kidney did not exert a direct effect on contralateral RBF or PG concentration. Haemodynamic changes in PUUO in vivo are associated with alterations in renal PGs. PMID- 7879313 TI - Lack of effect of carbon monoxide inhibitor on relaxation induced by electrical field stimulation in corpus cavernosum. AB - Carbon monoxide has been proposed as a possible neurotransmitter because of its ability to bind to the iron atom of the heme of guanylyl cyclase, which is similar to that of nitric oxide. To determine whether carbon monoxide exerts an effect on the penis, strips of rabbit corpus cavernosum were mounted in an organ bath for isometric tension studies and the effect of zinc deuteroporphyrin, an inhibitor of heme oxygenase which metabolizes hemoprotein and releases carbon monoxide, on relaxation induced by electrical field stimulation (neurally mediated) was determined. Also observed was relaxation induced by electrical field stimulation after incubation with atropine and guanethidine to isolate nonadrenergic noncholinergic neurotransmission. Zinc deuteroporphyrin (10(-6) M, 10(-5) M, 10(-4) M and 3 x 10(-4) M) did not affect relaxation induced by electrical field stimulation in the absence or presence of guanethidine and atropine. Therefore, it appears that carbon monoxide does not contribute to neurally mediated relaxation of the rabbit corpus cavernosum. PMID- 7879314 TI - Nitinol urethral stents: long-term results in dogs. AB - No information has been available to date on the long-term behavior of nitinol (nickel-titanium alloy) urethral stents. In the present study, prostheses of this type were implanted in 18 German shepherd dogs in order to evaluate the reaction of the mucosa, muscles and periurethral tissue. Follow-up examinations performed after 1 week, and 1, 3, 6, 12 and 18 months included urine, macroscopic, radiologic, histologic and scanning electron microscopic analyses. Despite the excellent biocompatibility of the material, with no evidence of foreign body reactions or corrosion, there were no complete incorporations of the stent by epithelialization. Clinical application therefore appears to be problematic. PMID- 7879315 TI - Reduction of vitamin D induced stone formation by calcium. AB - Investigations were carried out as to whether cytoprotective agents such as calcium antagonists can influence vitamin D induced nephrolithiasis. Increased vitamin D levels are found in 10-30% of all calcium oxalate stone formers. Male rats were assigned to one of the following groups: (1) 1,25 dihydroxycholecalciferol (DHCC) (n = 8), (2) 1,25-DHCC + calcium antagonist Goe 6070 (a new 1,4-dihydronaphthyridine, Goedecke, Berlin) (n = 8), or (3) control (n = 8). 1,25-DHCC was administered for 6 days (120 pmol/24 h s.c.), Goe 6070 (1 mg/kg/24 h) by gavage. Clearance studies were performed on day 6. Kidneys were taken for histological examination and determination of calcium tissue content. 1,25-DHCC induced substantial concrement formation, which could be significantly limited by Goe 6070. The calcium tissue content was also reduced (0.17 vs. 0.04 mg/100 mg dry weight). 1,25-DHCC induced a dramatic fall in the glomerular filtration rate (GFR) (3.84 ml/min per kilogram). This reduction could be almost completely inhibited by the concomitant application of Goe 6070 (9.4 ml/min per kilogram; control 10.7 ml/min per kilogram). Goe 6070 did not influence the calcium handling. The results demonstrate a protective effect of Goe 6070 on vitamin D induced nephrolithias. The histological pattern (intracellular and membrane-bound concretions) and the fact that biochemical parameters were not influenced significantly by Goe 6070 indicate that cellular proceses are important for 1,25-DHCC-induced nephrolithiasis. PMID- 7879316 TI - Epidermal growth factor receptor gene expression and binding capacity in renal cell carcinoma, in relation to tumor stage, grade and DNA ploidy. AB - Epidermal growth factor receptor (EGFr) was studied in 19 renal cell carcinomas using competitive binding analysis and solution hybridization assay. EGFr binding capacity and EGFr mRNA expression were significantly higher in tumors in comparison with kidney cortex tissues. The EGFr binding capacity was higher in diploid than in aneuploid tumors. No differences in binding capacities or mRNA expression between different tumor grades or stages were demonstrated. It was concluded that EGFr is overexpressed in renal cell carcinoma, although with no relationship to tumor characteristics. PMID- 7879317 TI - Role of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function associated antigen-1 (LFA-1) in peripheral blood mononuclear cell activation by human renal carcinoma cells. AB - We examined the role of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) during the activation of peripheral blood mononuclear cells (PBMCs) by the human renal carcinoma cell line CaKi-1. ICAM-1 antigen expression was induced on CaKi-1 cells by incubation with either phorbol 12-myristate 13 acetate (PMA) or interferon-gamma (IFN-gamma). Following a thorough washout of PMA and IFN-gamma and subsequent paraformaldehyde fixation, CaKi-1 cell monolayers were cocultered with allogenic PBMCs. While PMA-treated CaKi-1 cells induced PBMC proliferation and interleukin-2 receptor antigen expression, this was not the case for control or IFN-gamma-treated CaKi-1 cells. Furthermore, the induced PBMC proliferation was inhibited by specific monoclonal antibodies against ICAM-1 and LFA-1. Finally, although PMA induced human leukocyte antigen (HL)-A, B, C antigen expression on CaKi-1 cells, a monoclonal antibody against this antigen did not inhibit PBMC proliferation. We conclude that PMA can modulate CaKi-1 cells to stimulate allogenic PBMC proliferation in an ICAM-1/LFA-1 dependent, but HLA-A, B, C-independent, fashion. This stimulation might reside in the long-term activation of protein kinase C, induced by PMA. PMID- 7879318 TI - Basement membrane and tumor invasion: ultrastructural observations in the basement membrane of rat bladder with invasive transitional cell carcinoma induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. AB - This study describes ultrastructural alterations in the basement membrane (BM) of rat bladder with invasive transitional cell carcinoma (TCC) induced by N-butyl-N (4-hydroxybutyl)nitrosamine. Various alterations including thickening, degradation and neosynthesis were found in the bladder BM of one rat with invasive TCC. Focal destruction of both the BM lamina zones was found in addition to partially degraded BMs showing focal degradation and loss of only the BM lamina rara. Neosynthesis of complete BM including the lamina rara and lamina densa was observed surrounding the nests of carcinoma cells deep in the stroma, while neosynthesis of incomplete BM including only a lamina densa-like structure was also found around carcinoma cells which had just crossed the BM into the adjacent stroma from the original tumor masses. There was an increased hemidesmosomal frequency in some areas of thickened BM, and focal loss of hemidesmosome in the areas of degraded BM. It is suggested that BM degradation may take place in two steps, and that BM neosynthesis may also be a two-step process in invasive TCC of rat bladder. PMID- 7879319 TI - Immunoscintigraphy with iodine-131-labelled monoclonal antibody AUA1 in patients with transitional cell carcinoma of the bladder. AB - The monoclonal antibody AUA1, labelled with 2 or 3 mCi iodine-131, was administered intravesically to 11 patients with known or suspected bladder carcinoma and was kept in the bladder for 1 h. All patients underwent immunoscintigraphy of the bladder at 2 h and three patients also at 20 h after instillation. Conventional histological and immunohistochemical examinations were performed on tissue samples from tumour and normal areas taken during cystoscopy, carried out 24-h after the instillation. Transitional cell carcinoma of the bladder was present in nine patients whereas dysplastic and normal urothelium was found in the remaining two patients, respectively. Six out of nine tumours were successfully imaged at the 2-h scan. Normal urothelium showed no uptake while dysplastic urothelium was positive on imaging. Successful detection was correlated with size and grade of tumour in almost all cases. Tumors with a diameter of 1 cm or less were not detected. Four out of five grade II tumours and two out of three grade III tumours were detected with this method. The method is a promising one although further studies using more suitable isotopes and/or monoclonal antibodies are required to increase its sensitivity. PMID- 7879320 TI - [Is orthotopic ileal neobladder an acceptable form of urinary diversion from the viewpoint of the patient?]. AB - In 19 patients with bladder cancer who required cystectomy, an orthotopic ileal bladder was created. The patients were followed up for an average of 36 months (12-60 months). In this study we present the early and late postoperative complications, the survival data, quality of life assessment, data from urodynamic investigations, metabolic changes and the situation in the upper tracts. Postoperative complications requiring reoperation occurred in 11% in the early postoperative and in 27.7% in the late postoperative phase. Two of 19 patients died from cancer 18 and 26 months after cystectomy. A further patient had an urethral recurrence and the cancer is progressing further. Questionnaires showed that 80% of our patients were satisfied with their new bladder. Eighty percent were continent during the day and at night. Stress incontinence (II-III) occurred in only 2 patients (12%). All patients were impotent, but in 5 SCAT therapy made intercourse possible. The metabolic acidosis required oral alkalization in 60%. Dilatation of the upper urinary tract was seen in 6% of the renal units. We conclude from our experience that an orthotopic ileal neobladder is an excellent method of urinary diversion after cystectomy. PMID- 7879321 TI - [Treatment of rectal injuries with vesicorectal fistulization in radical prostatectomy]. AB - In the literature many different ways are described of treating rectal injured during radical prostatectomy. Therefore, following this procedure we evaluated our patients with rectal injuries. Rectal injury occurred in 16 of 299 patients with radical prostatectomy for treatment of localized prostate cancer. Seven developed a vesicorectal fistula, 4 of whom needed no further surgical intervention. Only 3 (1%) had to undergo an additional operation. PMID- 7879323 TI - [Effect of extracorporeal shockwave therapy on tendinosis calcarea of the shoulder. A preliminary report]. AB - The aim of a prospective study was to examine the effects of high energetic shock wave treatment on the course of calcareous tendinitis of the shoulder. 20 patients were entered into the study. Shock waves were applied to the calcifications with a Lithotripter MFL 5000 in two sessions of 2000 impulses each. The shock wave producing energy was 18 kV-22 kV. 6 and 12 weeks after treatment subjective and functional condition was checked by means of a 100 points functional score; all patients underwent x-ray control and MRI imaging. RESULTS: After 12 weeks 14 patients showed a marked improvement of symptoms, the average improvement on score measuring 25 points. The x-rays of 7 patients showed a complete resorption of the calcifications, in 5 cases partial disintegration of the calcium deposits was seen. The overall morbidity was low with 14 patients developing transient hematomas; MRI imaging showed no severe damages of bone and soft tissue. PMID- 7879322 TI - [Results of color-coded duplex ultrasound diagnosis (angiodynography) after intraurethral administration of PgE1 in erectile dysfunction]. AB - When the pathomechanism of erectile dysfunction is obscure, intraurethral administration of prostaglandin E1 is followed by a marked increase in blood flow velocity in the penile arteries as measured by color-coded Duplex sonography. This increase compares to that following intracavernous administration of half the dose of prostaglandin E1. The difference in the effects after intraurethral and intracavernous administration is the missing rigidity after intraurethral application; there must be a loss of pharmacological efficacy to the smooth penile muscles. Clinical efficacy is to be expected with higher intraurethral dosage. PMID- 7879324 TI - [Asynchronous bilateral hydronephrosis in retroperitoneal fibrosis with an interval of 44 months]. AB - The case of a man, now aged 53 years, with bilateral, asynchronous (44 months apart) hydronephrosis caused by retroperitoneal fibrosis is reported. A review of the literature with reference to the reported side effects of H2-antagonists (which the patient had taken immediately before developing the hydronephrosis) does not reveal any definite relation between the disease and these drugs. Stenosis and medialization of the middle third of the ureter (mostly bilateral) should suggest retroperitoneal fibrosis to the urologist, as early surgical treatment is mandatory to preserve renal function. Postoperatively, immunosuppression for at least 6 months is highly recommended to prevent recurrence. PMID- 7879325 TI - [Erysipelas and elephantiasis of the scrotum. Surgical and drug therapy]. AB - Elephantiasis is the outcome of persistent lymphedema. It is refractory to different therapy modalities. The social approachability of patients with this disease is impaired by severe functional and cosmetic disturbances. The causal relationship between etiology and recurrent disease is demonstrated by two cases. Treatment options are discussed. Radical surgery is decisive for primary success since chronic inflammation and chronic edema support each other. Metabolic equilibrium, disinfecting skin areas and antibiotic prophylaxis are urgent steps in the successful treatment of Erysipelas disease. PMID- 7879326 TI - [Indications]. PMID- 7879327 TI - [Urine cytology]. PMID- 7879328 TI - Current management of ureteroceles. PMID- 7879329 TI - The case for primary endoscopic management of upper urinary tract calculi: I. A critical review of 121 extracorporeal shock-wave lithotripsy failures. AB - OBJECTIVES: To define those patients with upper urinary tract calculi who are more likely to have an unsuccessful outcome from extracorporeal shock-wave lithotripsy (ESWL). METHODS: A critical prospective analysis of 121 patients, referred to two university centers after ESWL had been exhausted as a treatment modality for upper urinary tract calculi, was performed. Patients were subdivided into the following groups: failure to clear fragments, failure to fragment, difficulty in calculus localization, and failure due to inherent upper urinary tract obstruction. Other important variables include the type of extracorporeal lithotriptor used, number of treatment sittings before referral, calculus location, calculus composition, patient body habitus, and the imaging leading to and associated with extracorporeal therapy. RESULTS: Large renal calculi (mean, 22.2 mm) and those within dependent or obstructed portions of the collecting system were frequently referred for endoscopic management after failed ESWL. Steinstrasse can be an extremely morbid complication from ESWL and in this series was associated with irreversible loss of renal function and ureteral stricture disease. Extracorporeal lithotripsy of infectious calculi can be associated with severe septic complication. Inadequate preoperative and intraoperative imaging and morbid obesity were also associated with failure. Second- and third generation lithotriptors were represented in greater numbers than the Dornier HM 3 in this group of ESWL failures. CONCLUSIONS: ESWL remains the treatment of choice for moderately sized, uncomplicated renal calculi. Large calculi, those within obstructed or dependent portions of the collecting system, and those composed of calcium oxalate monohydrate, frequently fail ESWL. Training in the more technically challenging aspects of endoscopic lithotripsy must be encouraged. PMID- 7879331 TI - Xanthogranulomatous pyelonephritis, the gatekeeper's dilemma: a contemporary look at an old problem. AB - OBJECTIVES: To review 12 patients with a clinicopathogenic diagnosis of xanthogranulomatous pyelonephritis (XGP) and to determine if a computed tomography (CT) scan is the imaging procedure of choice for diagnosis. METHODS: A retrospective review, over the last 12 years, of patients with XGP at our institution. RESULTS: Nine of 10 patients (90%) who were evaluated by CT scan had the correct diagnosis made prior to nephrectomy. The most common presenting symptoms and signs were flank pain (64%), leukocytosis (73%), and anemia (82%). Seventy-five percent of the patients had a ureteropelvic junction stone or a staghorn stone in the affected kidney at the time of clinical presentation. Proteus was the most common organism cultured. CONCLUSIONS: After reviewing the clinical features of these 12 patients, we recommended CT scan to evaluate the patient in whom clinical suspicion of XGP is entertained. CT has proven to be the most accurate imaging study to evaluate this disease. PMID- 7879330 TI - The case for primary endoscopic management of upper urinary tract calculi: II. Cost and outcome assessment of 112 primary ureteral calculi. AB - OBJECTIVES: To compare extracorporeal shock-wave lithotripsy (ESWL) with endoscopic lithotripsy to establish the more efficacious and cost-effective treatment for ureteral calculi. METHODS: The records of 112 patients with primary ureteral calculi treated at one center with either ESWL or endoscopic lithotripsy were retrospectively reviewed. Follow-up data at 1 and 3 months were obtained in all patients. Success was defined as complete clearance of a stone burden in the endoscopy group. In the ESWL group patients with a residual, asymptomatic 2-mm fragment were also considered successful treatments. The number of auxiliary procedures, retreatments, postoperative office visits, and imaging studies required before a patient was considered stone free was defined. The impact of these variables on global costs was carefully reviewed. RESULTS: Patients with ureteral calculi primarily treated with ESWL or ureteroscopic lithotripsy had stone-free rates after a single session of 45% versus 95% at 1-month follow-up, and 62% versus 97% at 3-month follow-up. Retreatment and auxiliary procedure rates were significantly higher in the ESWL group (31% versus 3%). The mean number of postoperative visits and imaging studies until a patient was stone free was also higher in the ESWL group (2.07 versus 1.13). Operative treatment costs were similar for both modalities, but overall costs weighed heavily against ESWL. CONCLUSIONS: ESWL remains the treatment of choice for moderately sized, uncomplicated renal calculi. In skilled hands, ureteroscopic lithotripsy is by far the most expeditious and cost-effective means of clearing a ureteral stone burden. PMID- 7879332 TI - Definitive tumor resection and percutaneous bacille Calmette-Guerin for management of renal pelvic transitional cell carcinoma in solitary kidneys. AB - OBJECTIVES: This study was done to evaluate the safety and initial efficacy of definitive tumor resection combined with percutaneous bacille Calmette-Guerin (BCG) for management of renal pelvic transitional cell carcinoma (TCC) in patients with solitary kidneys. METHODS: Eight patients with anatomically solitary kidneys, all of whom had a prior history of TCC elsewhere in the urinary tract, were treated with either partial nephrectomy (n = 2) or percutaneous resection (n = 6) combined with a 6-week course of topical BCG administered percutaneously. Seven (87.5%) of the 8 patients tolerated the complete BCG course without adverse effects. One patient required cessation of treatment for renal insufficiency, which resolved with discontinuation of therapy. Follow-up nephroscopy was performed 3 months after the initial tumor resection in 6 of the 8 patients, and all patients underwent regular follow-up surveillance at 3- to 6 month intervals thereafter with radiographic, cytologic, and, in some cases, ureteroscopic examinations. RESULTS: With follow-up ranging from 9 to 59 (mean, 22) months, local tumor recurrence has become evident in only 1 patient. Two other patients have developed distant metastatic disease, both of whom had invasive TCC elsewhere in the urinary tract prior to treatment of the upper tract tumor. CONCLUSIONS: Combining a 6-week course of percutaneously administered topical BCG with definitive tumor resection is generally well tolerated, and, ultimately, this protocol may result in a decreased incidence of local tumor recurrence in these high-risk patients. PMID- 7879333 TI - Comparison of bladder cancer outcome in men undergoing hematuria home screening versus those with standard clinical presentations. AB - OBJECTIVES: Because repetitive hematuria home screening with a chemical reagent strip can detect early stage bladder cancer (BC) in asymptomatic middle-aged and elderly men, the ability of this screening to effect earlier detection and reduce BC mortality was investigated. METHODS: Grades, stages, and outcomes of BCs detected by hematuria screening in 1575 men were compared with those of all newly diagnosed BCs in men age 50 years or older reported to the Wisconsin cancer registry in 1988. BC grades and stages were assigned by review of all pathology slides/blocks, and causes of deaths were determined from cancer registry records. As an additional control group, outcomes of BC cases diagnosed in men solicited to take part in screening, who declined, were also determined. RESULTS: The proportions of low-grade (grades 1 and 2) superficial (Stages Ta and T1) versus high-grade (grade 3) or invasive (Stage T2 or higher) cancers in cases detected by hematuria screening (screened cases) and those reported to the tumor registry (unscreened cases) were not significantly different (52.4% versus 47.7% in 21 screened and 56.8% versus 43.3% in 511 unscreened cases) (P > 0.20). Of the high grade or invasive cases, however, the proportion of late stage (T2 or higher) tumors was significantly lower in the screening-detected BCs compared to unscreened ones (P = 0.007). No screened case has died of BC (3- to 9-year follow up), whereas 16.4% of unscreened cases have within 2 years of diagnosis (P = 0.025). Twenty-three of 1940 (1.2%) men who were solicited but chose not to participate in screening were diagnosed with BC within 18 months after what would have been their last home screening date, compared with 1.3% of participants having BC detected by screening. Thus, screening participants and those who were solicited and declined had similar likelihoods of developing BC. CONCLUSIONS: Hematuria home screening detects high-grade cancers before they become muscle invading and significantly reduces BC mortality. PMID- 7879334 TI - Insight into mechanism of neodymium: yttrium-aluminum-garnet laser prostatectomy utilizing the high-power contact-free beam technique. AB - OBJECTIVES: The objective of this study was to define the actual mechanism of neodymium: yttrium-aluminum-garnet (Nd:YAG) laser prostatectomy achieved with the previously described contact-free beam technique using the Ultraline delivery system at high-power settings. METHODS: Transurethral Nd:YAG laser application was performed with the Ultraline side-firing laser fiber in canine and human prostates. Total or radical prostatectomy was performed after laser treatment to examine and measure laser tissue effects produced using the contact-free beam technique. RESULTS: Minimal actual tissue evaporation or vaporization was noted in either the canine or human prostate using this technique. The extent of tissue vaporization achieved was probably insufficient to produce clinically significant voiding outcomes acutely or chronically. However, this technique, using the Nd:YAG laser, produced excellent tissue coagulation and necrosis, similar to other laser delivery systems and reports dealing with laser coagulation prostatectomy. CONCLUSIONS: The primary mechanism accounting for therapeutic efficacy of the contact-free beam technique for Nd:YAG laser prostatectomy utilizing the Ultraline delivery system at high-power settings appears to be tissue coagulation with subsequent necrosis and slough, rather than tissue vaporization. This is consistent with the known tissue effects of the Nd:YAG laser wavelength in other systems. PMID- 7879336 TI - Distribution of intraprostatic hyperchoice lesions in infertile men. AB - OBJECTIVES: To determine whether intraprostatic hyperechogenic lesions seen on transrectal ultrasonography are related to infertility. METHODS: The transrectal ultrasonographic studies of 58 infertile men and 12 fertile controls who all had intraprostatic hyperechoic lesions were reviewed to determine the anatomic distribution of hyperechoic lesions within the prostate and their relationship to the ejaculatory ducts. RESULTS: Hyperechoic lesions were located in the region of the verumontanum in 62% of the fertile control subjects and only 22% of infertile patients (P < 0.05). In contrast, hyperechoic lesions were present in the region of the ejaculatory ducts in 75% of the infertile men and only 39% of the fertile controls (P < 0.05). CONCLUSIONS: Hyperechogenic lesions located within the verumontanum appear to be a normal finding in fertile men, whereas lesions located in the region of the ejaculatory ducts are more likely to be associated with infertility. PMID- 7879335 TI - Effects of nitric oxide on human and canine prostates. AB - OBJECTIVES: To determine whether nitric oxide (NO) is a mediator of prostatic smooth muscle activity. METHODS: Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of human and canine prostate. RESULTS: EFS alone elicited frequency-dependent contractions in preparations of human and canine prostates. The greatest contractile activity was achieved at 30 Hz. In the presence of 10(-5) M guanethidine (GUA) and 2 x 10(-6) M atropine (ATR), EFS elicited relaxation of canine prostate strips relative to baseline tension. A weak biphasic response consisting of initial relaxation and subsequent contraction relative to baseline tension was observed in the human prostate strips exposed to similar conditions. The smooth muscle activity observed in the presence of GUA plus ATR was attributed to nonadrenergic, noncholinergic (NANC) nerve transmission. 10(-4) M L-NG-nitroarginine methylester (NAME) significantly increased EFS-elicited NANC smooth muscle activity both in human and canine prostates. L-arginine, 10(-2) M, reversed the effect of L-NAME in human and canine prostates. Sodium nitroprusside, 10(-4) M, a donor of NO, caused relaxation of both human and canine prostates. The mean magnitude of the relaxant response/cross-sectional area in human prostate (2.64 +/- 0.4 g/cm2) was significantly greater than in the canine prostate (1.09 +/- 0.17 g/cm2) (P < 0.005). CONCLUSIONS: These results provide compelling evidence that NO plays a role in mediating contractile function of human and canine prostates. PMID- 7879337 TI - Frequency and characterization of p53 mutations in clinically localized prostate cancer. AB - OBJECTIVES: To determine the frequency of abnormal p53 expression and to characterize confirmed p53 mutations in tumors from patients with clinically localized adenocarcinoma of the prostate. METHODS: p53 protein nuclear accumulation was determined immunohistochemically in the initial diagnostic tumor specimens from 37 patients with clinically localized prostate carcinoma. Two primary antibodies were used on all specimens. Structural analysis of the p53 gene was performed using the methods of polymerase chain reaction (PCR)/single strand conformation polymorphism (SSCP) and DNA sequencing. RESULTS: In 1 of the 37 (2.7%) tumor specimens, intense p53 nuclear staining was demonstrated using either antibody PAb 1801 or CM-1. The staining in this case was heterogeneous, with approximately 40% of tumor nuclei staining for p53. This tumor specimen was microdissected and DNA was extracted. Following PCR amplification, abnormally migrating bands were noted on SSCP analysis of exon 8. DNA sequencing confirmed the mutation as a C-->A transversion in codon 281 (asp-->glu). PCR/SSCP analysis of exons 5 through 8 was also performed for seven additional tumors that were negative for p53 nuclear accumulation by immunohistochemical (IHC) methods. All of these specimens demonstrated wild-type p53. CONCLUSIONS: The results of this study confirm and extend our previous findings that p53 mutations are rare in clinically localized adenocarcinoma of the prostate. In detecting clonal p53 mutations, standard immunohistochemical technique correlates reliably with structural p53 gene analysis of the evolutionary conserved domains encompassing exons 5-8. Importantly, most reports have demonstrated that p53 mutations detected by IHC are a late step in the progression of prostate cancer and are associated with advanced disease, dedifferentiation, and the acquisition of androgen independence. PMID- 7879338 TI - Accuracy of the initial history and physical examination to establish the etiology of erectile dysfunction. AB - OBJECTIVES: Because of its implications for possible therapy, the ability to establish a diagnosis of erectile dysfunction (ED) solely on the basis of history and physical examination has been a matter of controversy. The determination of the etiology of ED based on history and physical examination is evaluated in this present study. METHODS: Consecutive patients presenting for evaluation of ED were evaluated by careful history, physical examination, psychologic evaluation, and RigiScan monitoring. They were then stratified into either organic or psychogenic groups based on each of these modalities. These diagnoses were then compared to a final diagnosis obtained through additional testing. RESULTS: History and physical examination had a 95% sensitivity but only a 50% specificity in diagnosing organic ED. The accuracy rates of history and physical examination in diagnosing ED were 80% and 60%, respectively. CONCLUSIONS: A multifaceted comprehensive approach is required to evaluate fully and to diagnose ED. PMID- 7879339 TI - Ureteropelvic junction obstruction in upper and lower moiety of duplex renal systems. AB - OBJECTIVES: To review our experience with ureteropelvic junction obstruction in a duplicated renal collecting system. METHODS: The records of 7 patients with ureteropelvic junction obstruction in a duplex collecting system were reviewed. In addition to routine demographics, each case was reviewed for presenting symptoms, site of obstruction, and type of surgical treatment. RESULTS: Three of the 7 cases involved obstruction of the upper pole moiety, and the remaining 4 involved the lower pole segment of a duplex system. Obstruction of the upper and lower pole segments was found in both incomplete and complete duplicated collecting systems. CONCLUSIONS: Careful preoperative evaluation of patients with ureteropelvic junction obstruction will usually identify segmental obstruction in a duplicated system. Treatment should be individualized based on site of obstruction and degree of function remaining in the affected segment. PMID- 7879340 TI - Variable expression of the congenital obstructive posterior urethral membrane. AB - OBJECTIVES: To assess the variability of membranous folds in the posterior urethra and their relationship to urethral obstruction. METHODS: Endoscopic video recordings of 19 boys with a membranous lesion in the posterior urethra were obtained over a 2.5-year period. Six had an endoscopy after a prenatal diagnosis of obstructive uropathy and 13 boys presented with either a urinary tract infection or hematuria. RESULTS: Young's type I and type III appearances were seen in all with an obstructive membrane, and those with a less obstructing membrane probably had incidental pathologic conditions. CONCLUSIONS: These observations support the thesis that the congenital attachment of the verumontanum to the anterior wall of the posterior urethra is the embryologic fore-runner to the congenital obstruction of the posterior urethra, and that there may be a variable degree of persistence of that attachment, which in some boys is not obstructive. PMID- 7879341 TI - Repair of obliterative vesicourethral stricture after radical prostatectomy: a technique for preservation of continence. AB - We present the open surgical repair of complete obstruction of the bladder neck unresponsive to endoscopic management. By combining abdominal and perineal dissection, partial pubectomy, and omental wrapping, repeat anastomosis is possible without the need for bladder tubularization. Two patients have been repaired successfully. Although both men presented with indwelling suprapubic tubes and a defect of greater than 1.5 cm, they are now voiding normally at 18 and 7 months post-operatively without the need for pads, medication, or instrumentation. Complete obliteration of the bladder neck after radical prostatectomy can be functionally reconstructed. Postoperative continence will depend on the function of the membranous urethra. If incontinence occurs, this can be managed in a reconstructed open urethra. PMID- 7879342 TI - T-tube drainage of infected penile corporeal chambers. AB - Insertion of semirigid penile prosthesis is a surgical option to correct male erectile dysfunction. Postoperative infection of penile prosthesis necessitates removal and drainage of corporeal chambers. We describe a technique to drain infected corporeal cavities with T-tubes. PMID- 7879343 TI - Laparoscopic nephrolithotomy: the value of intracorporeal sonography and color Doppler. AB - Laparoscopic nephrolithotomy was used as an alternative to open surgery in a patient who had failed extracorporeal shock-wave lithotripsy and whose anteriorly located stone-bearing calix precluded percutaneous extraction. Endocavitary ultrasonography and color Doppler render the procedure safe and effective; localization of the stone, selection of an optimal nephrotomy site away from large vessels and where cortical thickness is minimal, and control of fragment clearance are greatly facilitated. PMID- 7879344 TI - Bilateral congenital midureteral adynamic segments. AB - Two cases of congenital midureteral adynamic segments are presented. Both children were successfully managed with excision of the lesions and primary reanastomosis. Pathologic examination revealed probe-patent ureters with muscular disarray, suggesting functional obstruction. Appropriate management of the anomaly was dependent on precise radiographic localization of the area of narrowing, and for this retrograde urography was essential. Primary ureteroureterostomy was successful in both cases. In this report we discuss the diagnosis, embryology, radiographic evaluation, and management of this rate situation. PMID- 7879345 TI - Laparoscopic extraperitoneal bladder diverticulectomy: initial experience. PMID- 7879346 TI - Overstaging of transitional cell carcinoma: clinical significance of lamina propria fat within the urinary bladder. AB - Staging of transitional cell carcinoma of the bladder relies on an accurate assessment of the depth of tumor invasion within the bladder wall and surrounding structures. Fat adjacent to muscle invasive carcinoma is often interpreted to represent full-thickness invasion of the bladder wall with extension into the perivesical tissues. We present a case report highlighting our finding of significant regions of fat within the lamina propria of the urinary bladder and its clinical importance with respect to the overstaging of carcinoma of the bladder. PMID- 7879347 TI - Tubular ectasia of the rete testis: an ultrasound diagnosis. AB - Tubular ectasia of the rete testis is a rare benign entity that is often associated with some degree of obstruction at the epididymal level, either post traumatic or postinfectious in nature. Its characteristic ultrasound findings have been well described in the radiologic literature. We report 6 cases of dilated rete testis diagnosed by ultrasound at our hospital over a 2-year period. Recognition of tubular ectasia by ultrasound, in the appropriate clinical setting, may eliminate unnecessary testicular biopsy or orchiectomy. PMID- 7879348 TI - Testicular pseudotumor in the acquired immunodeficiency syndrome. AB - We describe a case of testicular pseudotumor evaluated with both diagnostic ultrasound (US) and magnetic resonance (MR) imaging. The findings were inconclusive and eventually radical orchiectomy and pathologic analysis were required to make the diagnosis. The typical US and MR findings of both inflammatory and neoplastic lesions of the testis are discussed. PMID- 7879349 TI - Subcutaneous urinary diversion utilizing a nephrovesical stent: a superior alternative to long-term external drainage? AB - OBJECTIVES: The use of external percutaneous nephrostomy drainage in patients with end-stage ureteral obstruction in whom ureteral stenting has failed presents significant compromises in the patient's quality of life. Toward this end, we present the initial experience in the United States with an intracorporeal nephrovesical stent. METHODS: We performed successful subcutaneous urinary diversion in 2 patients with malignant, metastatic periureteral obstruction. Both patients had previously been managed with a chronic percutaneous nephrostomy that was both painful and inconvenient. The nephrovesical stent was inserted utilizing percutaneous access to both the kidney and bladder followed by creation of a subcutaneous tunnel between the two sites. RESULTS: The nephrovesical stents are patent at 6 and 9 weeks postoperatively and both patients have had their nephrostomy tubes removed. Both patients have noted a marked improvement in their overall comfort and quality of life since the stent has been in place. CONCLUSIONS: Subcutaneous urinary diversion with a nephrovesical stent provides effective urinary drainage and may improve the quality of life of patients with malignant metastatic ureteral obstruction. Further long-term studies are needed. PMID- 7879351 TI - The economics of health care reform. PMID- 7879350 TI - Interleukin-6: a candidate mediator of human prostate cancer morbidity. AB - OBJECTIVES: Interleukin-6 (IL-6) is evaluated as a candidate mediator of morbidity in patients with metastatic adenocarcinoma of the prostate. METHODS: IL 6 concentration is measured by enzyme-linked immunoadsorbent assay (ELISA) in the ejaculate plasma of healthy men, in primary culture of prostate epithelial cells, in human prostate cancer cell line cultures and SCID mouse xenografts, and in the plasma of 73 men with metastatic adenocarcinoma of the prostate. RESULTS: High levels of IL-6 secretion are found in the normal human ejaculate, in prostate epithelial primary culture, and in three of four anaplastic, androgen-independent human prostate cancer cell lines tested. In contrast, the hormone-responsive and PSA-secreting cell lines and the hormone-independent line PPC-1 do not secrete detectable levels of IL-6 by ELISA: The acquisition of a p53 mutation in LNCaP-GW and PPC-1 is not sufficient to confer the phenotype of high IL-6 secretion. Seventy-three men with well-characterized, advanced, hormone refractory prostate cancer prior to suramin therapy are tested for incidence of abnormal circulating levels of IL-6. Plasma IL-6 levels have a bimodal distribution, with the upper quartile of patients having abnormal levels from 9 to 61 pg/mL. A direct comparison of the high and low serum IL-6 groups show that elevated IL-6 levels are strongly correlated with objective measures of morbidity: decreased hematocrit, hemoglobin, and serum cholesterol, and increased white blood cell count and serum lactate dehydrogenase levels all in the absence of clinical infection. CONCLUSIONS: These data show that IL-6 is a prostate exocrine gene product, a candidate mediator of prostate cancer morbidity, and a candidate marker of disease activity for prospective clinical testing. PMID- 7879352 TI - Hypovolemic shock and resuscitation. AB - Hypovolemic shock is the manifestation of hypoperfusion from inadequate intravascular volume resulting in cellular hypoxia. Early, effective treatment tailored to the individual patient will minimize morbidity and mortality. The causes and end-organ responses can differ with each patient, requiring an understanding of the underlying physiology and pathophysiology. Treatment always consists of oxygen and isotonic crystalloids and may require the use of colloids, corticosteroids, antibiotics, and vasomotor drugs. PMID- 7879353 TI - Acute respiratory distress. AB - The keys to differential diagnoses and anatomical localization for causes of acute respiratory distress are based on history and physical examination findings. The specific factors and therapeutic considerations for conditions associated with acute respiratory distress ranging from laryngeal paralysis to diaphragmatic hernia are examined. Additionally, the general approaches and principles to consider regarding oxygen therapy and ventilatory support are discussed. PMID- 7879354 TI - Management of life-threatening trauma. AB - The response to major traumatic injury is a clinical challenge for even a well trained hospital team. Efficient, effective treatment must be initiated as life threatening problems are identified, often without the benefit of a definitive diagnosis. Therapy focuses on maximizing oxygen delivery and oxygen utilization in a hypermetabolic patient by improving gas exchange and blood flow. An algorithmic approach to patient care during a fast-paced, high-stress resuscitation is known to optimize this therapy and to improve outcome. Even with their proven benefit in facilitating patient care, algorithms have inherent limitations that require attention and common sense on the part of the attending clinician. It is true that "trauma can take you anywhere" and even a minor injury, especially if improperly managed, can lead to life-threatening complications and death. No algorithm can include all of trauma and all the possible sequelae without being too difficult for practical application. The algorithms cannot include basic common sense, which, right or wrong, is assumed to be a part of each doctor's decision-making skills. The algorithms are inherently in series, whereas emergency patient care requires the management of complex problems in parallel. The clinician is required to understand the priorities outlined in the algorithms, to have the skill to identify life threatening problems, to use the appropriate protocol, and to move forward or backward in the protocol when the patient's condition demands a change of focus and priority. The algorithms enhance but are not a substitute for up-to-date medical knowledge, familiarity with anatomy, good clinical skills, and experience. Finally, although these algorithms are based on years of clinical experience, they have not been tested with the appropriate prospective clinical studies needed to generate veterinary outcome statistics. Future modifications in algorithm protocol will be based on such studies. PMID- 7879355 TI - Assessment and management of the hemorrhaging patient. AB - Trauma patients presenting to the veterinarian on an emergency basis commonly have bleeding injuries. Although mild hemorrhage is often self-limiting, severe hemorrhage may be lethal if not surgically controlled. Management of these patients requires rapid assessment and diagnostics so that appropriate treatment is provided in a timely manner. This article describes care of the hemorrhaging patient including assessment, immediate resuscitation, and principles of controlling the hemorrhage. External and surgical methods of treating hemorrhage are discussed, with a concentration on the surgical management of the hemorrhaging patient. PMID- 7879356 TI - Clinical approach to toxicities. AB - Toxicities are a common presenting complaint in the emergency department. This article discusses the clinical approach to the poisoned patient from the initial telephone call by the owner to presentation, management, and monitoring of the patient in the emergency department. Topics discussed include telephone triage, diagnosis, management, and monitoring of the poisoned patient. PMID- 7879357 TI - Hematologic emergencies. AB - The most common life-threatening hematologic emergencies include hemorrhage and severe anemia. Successful treatment of these conditions depends on the emergency veterinarian having a thorough understanding of the possible etiologies of these conditions, and a systematic approach to diagnosis and therapy. Use of blood component therapy can be a life-saving technique in these patients. The goal of this article is to familiarize the emergency veterinarian with a systematic approach to the diagnosis and treatment of hematologic emergencies. PMID- 7879358 TI - Emergencies of the female reproductive tract. AB - Emergencies of the female reproductive tract are common in small animal practice. The veterinarian must be familiar with normal and abnormal reproductive behaviors, as well as medical and surgical options available. Emergencies of the reproductive tract can be life-threatening for both dam and off-spring, requiring rapid diagnosis and assessment as well as aggressive treatment. With effective management, most of these conditions warrant a good prognosis. PMID- 7879359 TI - Acute vomiting. AB - Patients commonly present to the emergency clinician for evaluation of acute vomiting. The causes of vomiting range from trivial to life-threatening. The clinician must use the history, physical examination, emergency data-base, and abdominal radiographs to determine the severity of the underlying problem and the extent of the systemic side-effects of vomition. Based on this information, a plan can be devised for optimal emergency management of these patients. PMID- 7879360 TI - The acute abdomen. AB - Acute abdomen patients present a diagnostic and therapeutic challenge to emergency clinicians. The decision to perform surgery or to treat medically is often difficult to make and requires assimilating patient information, laboratory findings, radiological studies, and DPL. The importance of careful and repetitive PE cannot be overemphasized when managing these patients. If all diagnostics performed are not definitive and the patient continues to exhibit signs of abdominal pain, it is advisable to explore the abdominal cavity while administering supportive measures. Abdominal ultrasonography is emerging as a valuable diagnostic tool for the acute abdomen patient. Laparoscopy, CT, and CAD may also prove useful in certain cases. PMID- 7879361 TI - Systemic inflammatory response syndrome: septic shock. AB - The systemic inflammatory response syndrome (SIRS) is the body's response to a multitude of chemical mediators. Conditions inciting the release of these mediators include bacterial sepsis, viremia, pancreatitis, trauma, neoplasia, heat stroke, and many others. The key to the successful management of SIRS lies in anticipation and not reaction. Resuscitation of the patient to supranormal levels, coupled with aggressive monitoring and support of target organs are essential. PMID- 7879362 TI - The emergency care of traumatic wounds: current recommendations. AB - Emergency management of wounds involves examination and protection of the wound with a wet dressing (when possible) to prevent further contamination and desiccation. Analgesia (or preferably anesthesia) is provided and the patient and the wound are prepared for surgery. Copious amounts of lavage solution are used under moderate pressure. Proper and thorough debridement under irrigation is tedious and time consuming, but is the most important factor that influences subsequent wound healing. Incomplete removal of devitalized or contaminated tissue and debris are a common cause of wound infection, breakdown, and delayed healing. Wound closure is only accomplished when the veterinarian is certain that all devitalized and contaminated tissue has been removed and there is adequate skin. Covering the wound to heal by second intention or delayed closure should be considered more often in veterinary medicine. All too often, the wound is closed prematurely, resulting in dehiscence and infection a few days later. This provides a source of complications to the pet, as well as a source of dissatisfaction for the client. If, after initial debridement and irrigation, there is any doubt about the advisability of surgical closure, the clinician should cover the wound with a proper dressing and continue daily (or more often) dressing changes with local irrigation and debridement as required. Drainage of wound fluid is critical to healing in contaminated wounds. Wound fluids interfere with healing and increase the likelihood of infection. Passive drains (Penrose) are frequently used, often incorrectly. The exposed end of passive drains should be covered with a sterile, absorbent dressing. Active drainage is more efficient than passive drainage and can be accomplished with minimal additional skill and material. Improper use of drains can cause more problems than no drainage at all. Patients suffering painful traumatic (or surgical) wounds should receive analgesic medications. The patient's response to pain may cause immunocompromise, resulting in increased infection rate. It may also induce a hypermetabolic state that may result in impaired wound healing, multiple organ dysfunction, and, possibly, death. Swelling in the area of wounds can create tension on the wound, which compromises the blood supply. Light pressure bandages are recommended to minimize swelling. Nutritional considerations should be given to the wounded patient. Additional protein, vitamins, and minerals may be required for immune function and wound repair.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7879363 TI - First aid, transport, and triage. AB - A favorable outcome for a patient suffering acute trauma or disease is more likely if prehospital first aid can be administered. Veterinary facilities should teach their clients about first aid and transport and be able to give instructions over the telephone. Once a patient arrives at a veterinary facility, the entire staff should be prepared so that triage, the primary survey, resuscitation and stabilization, and the secondary survey may be performed efficiently and effectively. PMID- 7879364 TI - Select committee calls for an end to quarantine for EU cats and dogs. PMID- 7879365 TI - Wooldridge Memorial Lecture--realities of research. PMID- 7879366 TI - Effects of handling and transport on bruising of sheep sent directly from farms to slaughter. AB - The bruising of sheep carcases results in economic losses to the meat industry and is one indicator of welfare problems before slaughter. In this study the numbers of potentially bruising events and the transport conditions of sheep taken directly from farms to a slaughterhouse were related to the occurrence of bruising. Among 2509 sheep in 79 groups the mean number of potentially bruising events was 0.71 per sheep, and they were due mainly to riding behaviour and wool pulls which occurred most commonly while they were being handled before being stunned. The mean proportion of bruised carcases per group was 0.25, and there was a mean of 0.31 bruises per sheep. Most bruises occurred on the back and were bright red and between 2 and 4 cm in diameter. The mean space allowance per animal on the vehicles was 0.29 m2 and the mean journey time was 251 minutes. A logistic model was used to examine the effects of seven variables on the risk of bruising. More space per animal, transport on the lower deck or at the front of the vehicle, and increased handling all increased the risk of bruising. There were some significant correlations between potentially bruising events and bruising on specific parts of the body. PMID- 7879367 TI - The outcome of widespread use of semen from a bull persistently infected with pestivirus. AB - During the certification of the bulls at an artificial breeding centre for freedom from pestivirus infection, a single viraemic bull was identified, and further testing confirmed that it was persistently infected. The two-year-old bull was healthy and of similar bodyweight to its peers. Its semen was of normal quality on the basis of density, motility and morphological criteria. Approximately 600 doses of semen had been distributed for sire evaluation purposes to 97 dairy farms. An examination of the breeding records indicated a first service conception rate of 38 per cent. All but one of the 162 cows inseminated with the bull's semen were seropositive compared with 95 of 143 cows (66.4 per cent) inseminated with semen from other bulls. Virological studies of the 61 calves sired by the persistently infected bull revealed that two were persistently infected, but that the others were healthy and uninfected. It was concluded that the semen from this bull was a potential source of pestivirus infection for 'clean' herds. PMID- 7879368 TI - Sandwich ELISA detection of Mycoplasma bovis in pneumonic calf lungs and nasal swabs. PMID- 7879369 TI - Four functional mammary glands in a goat. PMID- 7879370 TI - Future of the State Veterinary Service. PMID- 7879371 TI - Realities of research. PMID- 7879372 TI - Resistance to levamisole. PMID- 7879373 TI - Canine angiostrongylosis. PMID- 7879374 TI - Favus in an ostrich. PMID- 7879375 TI - Transport of live animals. PMID- 7879376 TI - Patterns of Trypanosoma vivax and T. congolense infection differ in young N'Dama cattle and their dams. AB - Trypanosome infection was detected by the dark ground/phase contrast buffy coat microscopic technique in N'Dama cattle in a high natural tsetse challenge situation in Zaire. The data were used to compare the pattern of infection in very young animals and in their dams, and to evaluate how the pattern evolved in calves from birth to maturity, and thereafter in the different age groups represented by their dams. Five hundred and fourteen calves were evaluated at 3 week intervals for an average of 26 months each, over varying periods between birth and 42 months of age. Two hundred and sixty nine dams had matching records from parturition to calf weaning at 10 months. One month after weaning, animals were equally infected with Trypanosoma vivax and Trypanosoma congolense. From then until 42 months, the proportion of time an animal was infected with T. vivax relative to T. congolense gradually decreased. In the dams this trend continued from 4 years to at least 8 years of age by which time T. vivax infection was only one-third that of T. congolense infection. This finding is regarded as strong evidence of the ability of N'Dama cattle, in this region of Africa, to acquire significant control of the development of parasitaemia following T. vivax infection but apparently not following T. congolense infection. Pre-weaner calves, grazing with their dams, appeared to have considerable protection from, or be more resistant to, both T. vivax and T. congolense infections compared with their dams and to their own immediate post-weaning situations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879377 TI - Quantitative phenotyping of N'Dama cattle for aspects of trypanotolerance under field tsetse challenge. AB - Matching animal health and performance data were recorded over the 2 year period from weaning at 10 months of age on 255 N'Dama cattle in a high natural tsetse challenge situation in Zaire. Four parameters that are regarded as possible indicators of trypanotolerance, species of trypanosomes detected, length of time parasitaemic, intensity of parasitaemia (parasitaemia score), and anaemic condition as estimated by packed cell volume (PCV) values, were measured and the relative effects of changes in these parameters on trypanocidal drug requirements and growth were assessed. The effects of species of trypanosome on drug requirements and growth were directly measurable. In the case of the other three indicators, the effects on drug requirements and growth that would be brought about by a change of one standard deviation in each were calculated. This allowed comparison of similar sized changes in these three indicators that are of necessity recorded in dissimilar units. Trypanosoma vivax and Trypanosoma congolense infections had equal effects on the number of trypanocidal drug treatments required, an average of 0.61 treatments being administered to each infected post-weaner. A reduction of one standard deviation (SD) in length of time infected reduced the number of treatments required by 0.23 or 36% and an increase of 1 SD in PCV reduced the number required by 0.27 or 43%. Changes in parasitaemia score were not important. In the case of growth, a T. congolense infection reduced growth by 12.4 g day-1 or 8% more than a T. vivax infection. A reduction of 1 SD in length of time infected increased growth by 9.8 g day-1 or 6.5%, a reduction of 1 SD in parasitaemia score increased growth by 9.0 g day-1 or 6.0%, and an increase of 1 SD in average PCV increased growth by 8.4 g day-1 or 5.6%. The necessity to simultaneously measure the four criteria is clearly indicated by their approximately equal effects on the final performance trait of daily liveweight gain. Thus, absence of information on any of these criteria would significantly affect the accuracy of the estimate of an animal's overall trypanotolerance phenotype in this central African situation and reduce the progress possible in production projects involving N'Dama cattle. PMID- 7879378 TI - Reduction of Haemonchus contortus infective larvae by three nematophagous fungi in sheep faecal cultures. AB - The reduction of Haemonchus contortus (L3) infective larvae in sheep faecal cultures caused by the action of three nematophagous fungi conidia was evaluated in vitro. Addition of 20,000 conidia of Monacrosporium eudermatum, Arthrobotrys oligospora and Arthrobotrys robusta per gram of faeces caused a reduction of 95.7%, 98.3% and 10.1%, respectively, compared with the control group. A 97.4% reduction was observed when combined conidia of the three fungi were used. Total reduction of the larval population was observed by addition of the three fungi at 100,000 conidia per gram of faeces. PMID- 7879379 TI - Clinical prophylactic activity of melarsomine dihydrochloride (RM 340) against Dirofilaria immitis in heartworm-naive beagles exposed to natural infection in three southeastern states. AB - Melarsomine dihydrochloride (RM 340), a drug being developed as an adulticide for treatment of heartworm (Dirofilaria immitis) infection in dogs, was safe and highly effective as a clinical prophylactic agent against naturally acquired infections using Strategic and Tactical Treatment Programs. The Strategic Program involved treatment every 4 months (three series of treatments per year), disregarding the mosquito season (MS), to clear the existing infection at each treatment. The Tactical Program consisted of two series of treatments per year, 4 months apart, with the first one given about the middle of the MS (August) and the second one given after the end of the MS (December). Melarsomine was administered as two i.m. injections (lumbar muscles) of 2.2 mg kg-1 given 3 h apart. A total of 90 heartworm-naive beagles and a number of microfilaremic 'seed' dogs were used. Three similar experiments (30 beagles per experiment) were conducted at selected areas (Georgia, Florida, Louisiana) known to be enzootic for heartworm. At each site, 30 beagles were allocated to six groups of five dogs each, and four of these groups were placed outdoors in April of 1988. Two groups (control and treated) were exposed for 12 months, and the treated group was given melarsomine at 4, 8, and 12 months after exposure was started (Strategic Program). Another group was exposed for 8 months and treated with melarsomine at 4 and 8 months (Tactical Program). One group of tracer (sentinel) beagles was exposed from April to August 1988, one group from August to December 1988, and another from December 1988 to April 1989. April-August and August-December tracers served as controls for the tactically treated dogs. After exposure, all dogs were held indoors for 5 months before necropsy. Blood was collected at 4-5 month intervals and examined for microfilariae (MF) and adult heartworm antigen (enzyme-linked immunosorbent assay, ELISA). Treatment by the Strategic Program was 99% effective, with only one of the total of 15 treated dogs harboring any worms (a single female) at necropsy. Thirteen of the 14 control dogs (93%) exposed for 12 months became infected, with average worm recoveries of 6.8, 5.4, and 25.2 (range 1-45) for the Georgia, Florida, and Louisiana sites, respectively. All of the 13 heartworm-infected control dogs were antigen positive, and 12 of these were also MF-positive, while none of the strategically treated dogs was either antigen- or MF-positive at necropsy. Tactical treatment of the total of 14 dogs twice per year was 100% effective.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7879380 TI - Use of melarsomine dihydrochloride (RM 340) for adulticidal treatment of dogs with naturally acquired infections of Dirofilaria immitis and for clinical prophylaxis during reexposure for 1 year. AB - Heartworm-infected dogs were treated therapeutically with a new heartworm adulticide (melarsomine dihydrochloride, RM 340) and then put on a Strategic Program with treatment every 4 months for clinical prophylaxis to take advantage of the drug's potent activity against 4-month-old immature as well as adult Dirofilaria immitis. Ten random-source dogs with naturally acquired heartworm infections (microfilariae- and antigen-positive) were given melarsomine (2.2 mg kg-1 twice 3 h apart) by i.m. injection in the lumbar muscles to clear their existing infections. They were then placed outdoors (August 1988) in a high-risk area in Georgia (USA) for heartworm transmission and given melarsomine at the same posology every 4 months (Strategic Program) for 12 months as a clinical prophylactic measure. Five nontreated heartworm-naive beagles placed at this site during the same period served as 'controls' to monitor heartworm transmission. After exposure for 12 months, the ten treated and five 'control' dogs were taken indoors and held for 5 months. Microfilaremia and antigenemia levels were monitored in both groups by testing at 4-5 month intervals throughout the study and the intensity of infection was determined at necropsy. Microfilaremia levels in treated dogs dropped dramatically following the initial therapeutic treatment and remained either negative or low. Only two of the five 'control' dogs became microfilaremic, and this occurred near the end of the study. Nine of the ten treated dogs were antigen-negative 4 months after the initial therapeutic treatment, and all of them were antigen-negative at all bleedings thereafter. Four of the five 'control' dogs were antigen-positive at necropsy, and only one of these was positive 4 months earlier. Based on these antigen data, the initial treatment cleared 90% of the dogs of worms, and no worms were detected in any of the treated dogs thereafter. However, it is possible that undetectable immature heartworms were present. Although all of the treated dogs were antigen-negative at necropsy, three of them had a total of eight heartworms, seven of which were clearly immature, as determined by worm length measurements, and the remaining worm was a young adult female that was probably too young to be detected. All of the five 'control' dogs had heartworms (average 7.4; range 1-16), and about half of these worms were clearly immatures. Therapeutic treatment followed by strategic treatment with melarsomine every 4 months during reexposure was at least 89.2% effective overall.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7879381 TI - Metabolic labelling of wild and laboratory subspecies of the trichostrongyle nematode Heligmosomoides polygyrus. AB - The immunological, biochemical and taxonomic relationship between wild and laboratory subspecies of Heligmosomoides polygyrus was studied by metabolically labelling parasite proteins with [35S]-methionine. Much variability, both in content and synthesis of proteins was observed between the two subspecies. Laboratory female worms had a higher protein content and incorporated more radioactive label into somatic proteins than their wild counterparts. Incorporation of radioactivity into excretory/secretory (ES) proteins, predicted to contain important antigens, demonstrates a major reduction in synthesis of proteins with molecular weights 66, 55, 43, 41, 40, 39, 37, 28 and 16 kDa by laboratory females. These differences in protein synthesis might explain the differing infectivities of the two subspecies when passaged in inbred laboratory (Mus musculus) and wild (Apodemus sylvaticus) mice. PMID- 7879383 TI - Infection pattern of Cryptosporidium and Giardia in calves. AB - Faecal samples were collected weekly over a 3 month period from 0- to 20-week-old calves on an Ohio dairy farm, and examined for Cryptosporidium oocysts and Giardia cysts by a quantitative direct immunofluorescence assay. Oocysts and cysts were detected as early as 4 days of age. Shedding of Cryptosporidium oocysts peaked at 1 week and was low by 3 weeks. Some calves, however, continued to pass low numbers of oocysts. Shedding of Giardia cysts peaked at 2 weeks of age with high levels maintained until 7 weeks of age. Most calves continued to pass low numbers of Giardia cysts after weaning. Cumulative infection rates for both Cryptosporidium parvum and Giardia sp. were 100%. PMID- 7879382 TI - Lymphocyte proliferative responses and the occurrence of dermatophilosis in cattle naturally infested with Amblyomma variegatum. AB - The proliferative response of lymphocytes from tick-infested Zebu type, N'Dama and Friesian cattle and acaricide-treated Zebu types and Friesians in concanavalin A (Con A) stimulated cultures was monitored regularly for periods ranging from 11 to 27 months. The numbers of ticks on the animals and the presence of dermatophilosis were also noted. The Friesian cattle carried most and the N'Dama fewest Amblyomma variegatum ticks. The tick-infested Friesians all developed severe clinical dermatophilosis within 5 months of becoming tick infested. Dermatophilosis lesions on the tick-infested Zebu type and N'Dama cattle were less common and less severe especially in the N'Damas. The proliferative response of lymphocytes from tick-infested Friesians in Con A stimulated cultures fell to almost half that of the acaricide-treated Friesians soon after the former became tick-infested. The tick-infested Zebu types also developed a depressed response compared with the tick-free Zebu group over a 27 month study period. However, the responses of the N'Damas was similar to that of the tick-free Zebu types. The addition of autologous serum to Con A stimulated cultures of lymphocytes derived from the tick-infested Zebu types and N'Damas suppressed their proliferative response compared with that of similar cultures for the tick-free Zebu types. PMID- 7879384 TI - The efficacy of ivermectin (pour-on) against the eyeworms, Thelazia gulosa and Thelazia skrjabini in naturally infected cattle. AB - Sixteen crossbred beef cattle, 6-8 months of age, were used to determine the efficacy of ivermectin in a pour-on formulation against natural infections of Thelazia spp. Cattle were weighed on Day 0, ranked in descending order by bodyweight and sequentially paired. Within each pair, one animal was randomly assigned to an untreated control group, while the other animal was treated with a pour-on formulation of ivermectin applied topically at 1.0 ml per 10 kg bodyweight to achieve a dosage of 500 mg ivermectin kg-1 body weight. On Day 14 all animals in both treatment groups were slaughtered. The eyes and surrounding tissues were removed and examined for eyeworms. A total of 86 adult worms (74 Thelazia skrjabini and 12 Thelazia gulosa) were recovered from the untreated control animals. T. skrjabini was found in seven, and T. gulosa in three, of the eight untreated control animals. Two T. skrjabini, one from each of two animals, were found on the surface of the eyes of cattle that had received ivermectin treatment. The reduction in the geometric mean number for T. gulosa collected from treated animals was 100% (P > 0.1) relative to controls, and 97.02% (P = 0.0025) for T. skrjabini relative to controls. PMID- 7879385 TI - [Cloning of DNA fragments containing promoter activity from Streptomyces mycarofaciens 1748]. AB - A DNA fragment containing promoter activity has been cloned from midecamycin producing strain (S. mycarofaciens 1748)., using promoter-probe plasmid vector pIJ486. The molecular size of this fragment was 2.3kb as shown by restriction analysis. A HindIII-HindIII 2.08KB DNA fragment obtained from the original fragment has been analysed by subcloning it into polylinker of vector pIJ486/7 which have opposite direction. The result showed that HindIII-HindIII 2.08kb DNA fragment has promoter activity in both direction. Transformants of plasmid containing this fragment in vector pIJ487 in S. lividans TK24 were resistant to Km in the level of 20mg/ml, but in vector pIJ 486 were resistant to the level of 3mg/ml. It indicated that a rather strong promoter activity region was in the HindIII/XbaI-HindIII direction. BamHI fragments (A-0.79kg, B-0.67kb, C-0.62kb) in 2.08kb DNA fragment have been studied in regards of their promoter activity. The result suggested that A-0.79kb region has the same promoter activity as in HindIII-HindIII 2.08kb DNA fragment. PMID- 7879386 TI - [Molecular cloning of the adherence gene cluster from uropathogenic Escherichia coli and preparation of its antisera]. AB - A genomic library of the uropathogenic E. coli J96 was constructed by using cosmid pHC79 as cloning vector. Two positive recombination cosmids which could express the adherence characters were acquired. From both cosmids a EcoRI fragment was subcloned into the vector pACYC184 by shot-gun method. Three colonies were found which exhibited MRHA and production of P Pili. One of them, pCT10/E. coli K-12 P678-54, was about 14.6 kb and was used to prepare the antisera. After absorption with pACYC184/E. coli K-12 P678-54 for three times, the antisera were revealed specific against the adherence gene cluster of uropathogenic E. coli by the SDS-PAGE and Western blotting of the P pilus crude extracts and the hemagglutination inhibition test. PMID- 7879387 TI - [Studies on the ecological distribution of Bacillus thuringiensis in forest soils of China]. AB - A total of 384 forest soils samples at 0-5cm depth collected from 8 forest site zones (13 Natural Reserves) in China were examined for the distribution of Bacillus and Bacillus thuringiensis. The 79 cultures (4.21%) in 1873 isolates of Bacillus collected referable to the Bacillus thuringiensis. Soil pH, moisture content and soil nutrient were determined. Rules of the ecological distribution of Bacillus thuringiensis of 8 forest site zones in China were analysed. Toxicities against 6 species of insect were tested. Strain some efficient serains were obtained. It was shown that resource of Bacillus thuringiensis is much fruitful in forest soils of China. PMID- 7879389 TI - [Numerical taxonomy of fifty two strains Streptomyces by whole-cell protein composition]. AB - By using SDS-PAGE, fifty two strains Streptomyces were analysed for whole-cell protein composition. Electrophore pattern was divided into fifty composition for numerical taxonomy. The clustering result indicate that all strain's similarity is over 72 percent and different strains in a species is over 84 percent. The most similar strains is 96 percent. PMID- 7879388 TI - [Subcloning and sequencing of promoter active DNA fragment from Streptomyces lividans]. AB - Random subfragments with strong promoter activities were isolated from 2. 1 kb fragment of pMG50-25 using a promoter-probe vector pIJ4083. One of the promoter active region was narrowed down to a 220bp sequence. Putative promoter regions, SD sequence and start codons were found. PMID- 7879390 TI - [Video-assisted thoracic surgery]. AB - Over the past two to three years video-assisted thoracic surgery has opened up new possibilities in diagnostic and therapeutic procedures. It is viewed as a sparing and quick alternative to thoracotomy and open operation for a number of indications including the treatment of pneumothorax, obtaining biopsies of undiagnosed diffuse or nodulary lung disease, as well as extirpation of peripheral pulmonary lesions. In oncological thoracic surgery it still remains to be verified whether the criteria of radicality are fulfilled by this new technique. Extipation of circumscribed, extrapulmonary benign tumours and cysts within the thoracic cavity will soon be routine procedures. The advantages lie in the minimally traumatizing surgical technique; as a result of avoiding thoracotomy postoperative pulmonary function is less restricted, there is less pain, earlier mobilization is possible and the period of hospitalization is reduced. In the majority of procedures the operative time is reduced as compared with open surgery. Our experiences in this field with 370 patients are briefly reported. Disadvantages are the loss of the possibility to palpate the lung and the thoracic cavity. The costs of employing this technique is discussed. Video assisted thoracic surgery has a promising future; it is estimated that 20% to 30% of all thoracic interventions will be performed by this technique. PMID- 7879391 TI - [Educational opportunities in minimally invasive surgery]. AB - Since minimally invasive surgery makes high demands on the skill, concentration and endurance of the surgeon, requisite training in this operating technique is of overriding importance. Basic training on pelvitrainers serves to enable the participant to become acquainted with the instruments and the video technique and to gain experience in handling the camera. A realistic simulation of intraoperative situations is not possible. With pulsatile organ perfusion (POP) nearly all abdominal, thoracic, vascular, urological and gynecological surgical procedures, as well as the encountered complications, can be imitated, widely replacing the need for animal experiments. Complex operations which are bound to anatomical structures, have to be practised on anaesthetized animals, as before. PMID- 7879392 TI - [The value of laparoscopy in diagnosis and therapy of the traumatized abdomen]. AB - The prognosis of abdominal trauma depends in most cases not only on the extent of existing injuries but also on prompt therapy. Thus, diagnostic measures have to clarify rapidly and accurately whether laparotomy has to be performed or not. Difficulties in decision for the surgeon arise especially in cases of abdominal trauma where diagnostic imaging (ultrasonography, CT scan) does not lead to clearcut results. From 1st June, 91 to 30th November, 93 we performed diagnostic laparoscopy in 18 cases of abdominal trauma. In 4 patients no injuries were discovered and 5 patients had negligible injuries so that no therapy was necessary. In 4 cases the detected injuries were managed laparoscopically, whilst the remaining 5 patients had to be laparotomied. Of the 11 patients who would normally have been laparotomied as a primary measure, laparotomy was avoided in 5 cases by performing a laparoscopy (45%). On the other hand, we detected injuries on laparoscopy in 3 of the 7 patients who would not have been laparotomied on the basis of the results of the prelaparoscopic investigations. In 2 of these patients the additional injuries would have led to later complications, which were avoided by timely laparotomy following laparoscopic diagnosis. In our opinion laparoscopy is not a substitute for proven diagnostic measures such as ultrasonography or CT scan. However, it is valuable extension of diagnostic and therapeutic methods on abdominal trauma. PMID- 7879393 TI - [Minimally invasive surgery--choledocholithiasis: therapeutic splitting]. AB - Patients with cholecysto- and choledocholithiasis may benefit from the advantages of laparoscopic cholecystectomy by intraoperative common bile duct exploration or preoperative endoscopic papillotomy (EPT) with stone removal. We performed therapeutic splitting in 94 patients. Morbidity was 4.2% and mortality was zero. A follow up study of 50 patients shows residual stones in 2% and papillary stenosis in 2%. We believe our results, supported by data on EPT in the literature, show that two-stage endoscopic stone removal prior to laparoscopic cholecystectomy is a safe and effective method for treating cholecystolithiasis combined with choledocholithiasis. PMID- 7879394 TI - [Laparoscopic therapy of choledocholithiasis]. AB - In the period November 1991 to October 1993 altogether 418 patients underwent laparoscopic cholecystectomy in our unit. Routine intraoperative cholangiography, a prerequisite for diagnosing choledocholithiasis, was successful in 99.3% of cases. 38 patients were found to have common bile duct calculi and their management and follow up are reported in this study. In 36 cases stones were successfully eliminated by means of the laparoscopic procedure, via the cystic duct in 22 cases and by choledochotomy in 14 cases. One patient required postoperative endoscopic papillotomy, and in the remaining case surgical management was changed to classical laparotomy and open choledochotomy. Postoperative complications occurred in five cases. One patient suffering from bacterial peritonitis underwent laparotomy on the 9th postoperative day, another with postoperative bleeding from the cystic artery was relaparoscopied on the same day as the minimal invasive procedure. One patient developed a liver abscess three weeks after operation, requiring drainage with the aid of ultrasound. A superficial wound infection in one patient and biliary leakage after removal of the T-tube in another patient both healed spontaneously. Our results are similar to those obtained with other therapeutic concepts. Because the papilla of Vater remains intract in minimal invasive surgery, which causes relatively little stress to the patient, as well as considering the economic advantages of a single step procedure, this management strategy can be recommended as a valuable alternative procedure. PMID- 7879395 TI - [The status of laparoscopic cholecystectomy in Austria. AMIC--Study Group for Minimally Invasive Surgery]. AB - The complete 1992 register of minimal invasive operations at all surgical departments in Austria has been compiled for the third year running, representing questionnaires returned from 107 departments reporting a total of 11,591 laparoscopic cholecystectomies (LC). Evaluation of the data from the 81 departments with a least 2 years' experience showed an increase of 56.60% in the number of LCs and an overall increase in cholecystectomies of 18.50% in comparison with 1991. Sonography and/or intravenous cholangiography remain the standard procedures for the pre-operative diagnosis of bile-duct concrements, undertaken in 98.05% and 71.70%, respectively, of all cases in 1992. Intra operative cholangiography has been implemented with increasing frequency (17.56% of all cases in 1992), especially in those departments with longer experience on LC. The conversion rate to open cholecystectomy was 6.09%, and the incidence of secondary cholecystectomy was 1.26%. The mortality rate was 0.11%. Our register now contains the data on 19,872 LCs. Our evaluation of the multicentric data aims at a complete documentation of the frequency of this surgical procedure and the incidence of complications in Austria with a view to establishing guidelines for the indications for LC and planning of this operation, as well as following up current trends in the regional implementation of LC in Austria. PMID- 7879396 TI - [Laparoscopy-assisted colon surgery--overview and personal experiences with 64 patients]. AB - The number of laparoscopic or laparoscopic-assisted operations in abdominal surgery constantly increases. 64 patients between February 1992 and November 1993 underwent a laparoscopic assisted colorectal procedure. In 5 cases laparotomy was necessary. There were only 4 complications: one subileus treated conservatively and one peritoneal abscess was drained successfully under sonographic guidance; furthermore there were a postoperative pneumonia and a prolapse of the greater omentum in the area pierced by a 10 mm-trocar. The oncologic criteria for the resection of malignant tumours can be fulfilled in laparoscopic surgery. Our first experiences indicate that the advantages for the patient in laparoscopic procedures of the colon/rectum are the same as have been reported in laparoscopic cholecystectomy. PMID- 7879397 TI - [Laparoscopic interventions in urology]. AB - From December 1991 to October 1993, 230 laparoscopic operations were performed for urological indications in 205 patients, including 48 children aged between 6 months and 14 years. The rate of intra-operative complications was 2.5%. Intra operative bleeding (2 patients), cardiovascular insufficiency (1 patient) and pneumothorax (1 patient) necessitated conversion to laparotomy in 4 patients. In another patient intra-operative bleeding occurred, which was successfully managed conservatively by means of blood transfusion. The only serious postoperative complication was a hernia at the entry site of a trocar in a 6-months-old child. A broad spectrum of different operations was performed, including diagnostic and therapeutic laparoscopy for cryptorchism and intersex states, varicocele ligature, pediatric hydrocele (transection of an open processus vaginalis), nephrectomy, ureterectomy, heminephroureterectomy, marsupialization of renal cysts and a lymphocele, pelvic and retroperitoneal lymphadenectomy, adrenalectomy, ureteral re-implantation, pyeloplasty, lumbar sympathectomy and herniotomy. The overall results were very satisfactory. PMID- 7879399 TI - [Preventive aspects of spinal diseases]. PMID- 7879398 TI - [Laparoscopic interventions in gynecology]. AB - Gynecological surgery is performed in a difficult anatomical area of vital organs close to the pelvic wall. It requires precise hemostasis to prevent blood loss and postoperative complications. Both blood loss and complications are reduced by pelviscopic operation techniques. Patients who undergo gynecological pelviscopic operations often experience in comparison to laparotomy less fever, require less postoperative analgesia and are able to tolerate a full diet within 24 hours of surgery. Very often they have a faster recovery and a shorter hospital stay than patients undergoing traditional abdominal or transvaginal operations. The endoscopic operative technique lays the foundation for minimal invasive surgery. The mainly organ-resecting gynecological laparotomy, aiming to avoid recurrence, is increasingly being replaced by pelviscopic organ preservative techniques. Meanwhile we tend to perform many hysterectomies laparoscopically assisted (LAVH). It avoids laparotomy in casesa of adhesions and high uterine tissue mass and seems to lower intraoperative risks such as infection by strong operative restriction of the vaginal approach. CISH (classic intrafascial S*E*M*M* hysterectomy, S*E*M*M denoting "serrated edge macro-morcellated") even leaves the pelvic floor intact. Furthermore, we perform pelviscopic operations in cases of endometriosis, benign tumors of the ovaries, ectopic pregnancies and genital malformations (i.e., Vecchietti genitoplasty in the MRK-syndrome). PMID- 7879400 TI - [Active and passive exercise therapy]. AB - Therapeutic exercise has a central role within physiatry and physiotherapy. Contrary to other forms of treatment, the patient does not passively absorb energy (i. e. electricity or heat) but has to supply the energy him/herself. Exercise therapy is the only causal therapy in physical medicine and it can be dosed such that it is almost always applicable. Particularly about the latter point there is much confusion: Measures of positioning like in Guthrie-Smith's apparatus equally belong to therapeutic exercise as sequential therapy with power machines. Thus many patients are not submitted to physiotherapy and therapeutic exercise in particular, which are admittedly based on empiricism rather than scientific evaluation. This review attempts to provide an overview of the various methods of exercise therapy--incomplete and prone to the authors own preferences. PMID- 7879401 TI - [Mechanotherapy]. PMID- 7879402 TI - [Electrotherapy]. AB - Physical therapy offers various modalities of treating back pain, one of them is electrotherapy. Besides the long known, low-frequency currents (galvanization, iontophoresis, impulse galvanization, diadynamic currents, TENS), medium frequency currents (interference current) are increasingly applied today, as they cause patients to a far lesser degree to experience the often unpleasant "sensation of current". In chronic pain, short and microwave treatment (high frequency), which are to be counted among the thermal therapies, have again and again proved to be beneficial. PMID- 7879403 TI - [Thermo- and hydrotherapy]. AB - Muscle spasm can be reduced by heat as well as by therapeutic cold. However, in upper motor neuron lesions, cold is more effective in reducing the spasticity. This effect lasts long enough to be of therapeutic value. Water immersion supports the reduction of muscle tone. Pain may be reduced by both thermal stimuli. The pain threshold seems to be elevated by the direct effect of both heat and cold on the free nerve endings and the pain-killing fibers. The tendency to bleed is increased with heat application and decreased with cold therapy. Edema resulting from trauma is increased with heat, and decreased in its development by cold application. Joint stiffness is decreased with heat application and increased with cold application. Water immersion removes weight from the joints and facilitates mobility. PMID- 7879404 TI - [Is systemic psychotherapy research possible?]. AB - With the growing importance of systemic therapies the interest in quality evaluation, at the one hand, and in a deeper understanding of therapy processes, at the other, becomes more and more important. Therefore the question is raising how to do psychotherapy research for systemic therapies in an adequate manner. Some possibilities will be discussed. As we will see, the existing field of process research offers a lot of theoretical conceptualizations and methodological tools for the understanding of dynamical patterns in psychotherapy. An example for the single case microanalysis of client-therapist interaction in a solution-oriented brief therapy illustrates one of several different ways in system-oriented psychotherapy research. PMID- 7879405 TI - [Psychological treatment approaches in pain. A comparative study of therapies in patients with chronic polyarthritis]. AB - The efficacy of psychological treatment to reduce pain has recently been shown in a number of studies. They are considered to enhance or even replace medical approaches in pain management, especially in chronic pain-states. The study reported here aimed to test two established (multimodal pain management, relaxation training) and one newly designed approach (visualization techniques) in comparison with a control group (medical treatment alone). The study was conducted with in-patients (N = 46; rheumatoid arthritis). Medical and pain data were gathered before and after treatment. Patients also filled out questionnaires in the beginning and at the end of the study assessing pain-experience, emotional states and capability to cope with pain. Patients participating in the multimodal pain management group and the visualization group profited from participation (especially in pain reduction) only if they gained substantially extents in the capability to cope with pain. Simply taking part in the groups and not reaching acceptable measures to cope with pain had no or negative effects. Both approaches were clearly above the control- and the relaxation-condition (relaxation participants were hardly better than the controls). The range of efficacy was broadest in the multimodal group (in addition to pain-reduction, substantial improvements in emotional states were obtained). However, visualization techniques, which were tested empirically for the first time here, can also be recommended as pain management therapy. PMID- 7879406 TI - [The Repertory Grid as a research instrument in inpatient psychotherapy. Possibilities of semantic construct analysis in patients with psychogenic pain]. AB - The Repertory Grid Technique provides a differential analysis of individual constructs ("hypotheses"), by which we structure the perception of our environment. In our study we investigated 35 psychogenic chronic pain patients at beginning and end of inpatient psychotherapy, whether semantic changes occurred in their construct system. We analysed these semantic changes using a categorial system, which was developed by Landfield (1971). This categorial system consists of 22 different categories, at which a rating system (by use of a manual) evaluates the appropriate semantic attachment of constructs of an individual repertory grid to these categories. Our study shows that contrary to our expectation psychogenic pain patients comparatively often described themselves with constructs, which expressed direct social interactions or emotions. However, this finding must be interpreted with some reservation, as our patient group probably is not representative for most of the chronic pain patients, which usually are hardly to motivate for inpatient (respectively outpatient) psychotherapy. Finally we investigated the semantic changes of the construct system during the course of inpatient psychotherapy--here we assume that the conceptualization of own theory guided categories will provide more clinically relevant or perspective results compared to the original category system of Landfield. PMID- 7879407 TI - [Reducing ambiguity: semantic statistical studies of "normal" probands, neurotic patients, borderline patients and schizophrenic patients]. AB - The present study tries to answer three questions: 1.) Do patients with neurotic disorders differ from normals by a stronger tendency to avoid or reduce ambiguity? 2.) Does the tendency to avoid or reduce ambiguity increase with increasing ambiguity of the stimulus? 3.) Does the avoidance or reduction of ambiguity increase with affects of anxiety and hostility? In order to answer these questions, Ertel's dogmatism-dictionary was applied to the answers of 30 normals, 30 patients with neurotic disorders, 30 borderline-patients, 25 acute and 25 chronic schizophrenics in the Holtzman Inkblot Technique (HIT). According to the results, (1) patients with neurotic disorders do not differ from normals by a stronger tendency to avoid or reduce ambiguity. 2.) The tendency to avoid or reduce ambiguity increases with measures of increasing stimulus ambiguity of the HIT cards in all diagnostic groups studied with the exception of chronic schizophrenics. As far as response ambiguity (variability of interpretation) is concerned, only in chronic schizophrenics the tendency to avoid or reduce ambiguity decreases with increasing response ambiguity. 3.) The avoidance or reduction of ambiguity increases with affects of anxiety and/or aggression assessed by HIT-measures in all diagnostic groups studied with the exception of normals and chronic schizophrenics. In both normals and chronic schizophrenics, the reduction of ambiguity decreases significantly with increasing anxiety, in chronic schizophrenics the reduction of ambiguity decreases significantly with an increase of low levels of aggression. PMID- 7879408 TI - [Age, sex and diagnosis-specific differences in play of preschool children with the Scenotest. A study of the constructive validity of observation systems]. AB - As there are only few observation systems designed for the age group of 4 to 6 year-old children, the scenotest is often used as a diagnostic instrument. Being a projective instrument with a psychoanalytic foundation studies aiming to examine the objectivity, reliability and validity are lacking. In the study presented different observation systems were developed to assess children's behavior while playing with the scenotest material and the construct validity was examined. It could be shown that the instruments are able to differentiate between the behavior of elder and younger children, boys and girls and more or less stressed mother-child-dyads. The results indicate that the construct validity of the three new instruments is good. PMID- 7879409 TI - [Increasing the reliability of anamnestic data by increasing the length of the interview]. AB - In accordance with the theory of mental tests in this study it was tried to improve the reliability of diagnostic interview data by enhancing the number of items concerning the same biographical topic (= homogeneous items). Reliability was defined as stability of the statements in repeated interviews. The reliabilities of three interview items concerning different topics were calculated. The interviews were carried out under two different conditions: Under the experimental condition (30 subjects) the item, of which the stability was calculated, was the last in a series of ten homogeneous items, under the control conditions (30 subjects) the item was the last in a series of ten heterogeneous items. Under the experimental condition the reliabilities of two items, concerning the diseases of children and concerning the school record, were significantly improved. Not improved was the reliability of the appraisal of parent's educational methods. The reliabilities of the interview data not seemed to depend on the age of the subjects. PMID- 7879410 TI - Nucleic Acid Vaccines, WHO, Geneva, 17-18 May 1994. PMID- 7879411 TI - Some general aspects of immunity to viruses. AB - Immunity to viruses reveals strength and limiting aspects of both. The role of viral antigen distribution and persistence in inducing T cell responses, in escaping from them or inducing and exhausting them in cytopathic viruses is compared with that for non-cytopathic viruses. Accordingly, vaccination may be protectively efficient, or not, and can shift the relative kinetics beneficially or, in rare cases, also in a harmful way. PMID- 7879412 TI - Protection of ferrets against influenza challenge with a DNA vaccine to the haemagglutinin. AB - Immunization of ferrets with a plasmid DNA expressing influenza virus haemagglutinin (pCMV/H1 DNA) provided complete protection from challenge with the homologous A/PR/8/34 (H1N1) influenza virus. Delivery of DNA-coated gold beads by gene gun to the epidermis was much more efficient than intramuscular delivery of DNA in aqueous solution. The antibody response induced by DNA delivered by gene gun was more cross-reactive than DNA delivered in aqueous solution or after natural infection. This novel approach to vaccination against influenza may afford broader protection against antigenic drift than that provided by natural infection. PMID- 7879413 TI - Direct gene transfer into muscle. AB - Gene therapy has great promise for the treatment and the prevention of a broad range of inherited and acquired diseases. Gene transfer methods currently explored include the use of viral vectors and physical-chemical methods. Plasmid DNA can be taken up by skeletal muscle cells in vivo without any special delivery mechanism and persist long-term in an extrachromosomal, non-replicative circular form. Thus, foreign genes can be expressed permanently in skeletal muscle. At present the efficiency of gene transfer is not high enough to treat genetic muscle diseases. However, even at the relatively low efficiency of expression we are able to achieve at present, plasmid DNA transfer seems to be a very promising way of programming cells in vivo to secrete proteins for immunization purposes. PMID- 7879414 TI - Direct gene transfer in skeletal muscle: plasmid DNA-based immunization against the hepatitis B virus surface antigen. AB - Direct gene transfer by intramuscular injection of plasmid DNA encoding an antigenic protein may be used for the purpose of immunization. DNA-based immunization may be of value for basic immunological research and vaccine development. Several factors influence the uptake and expression of plasmid DNA in skeletal muscle, which in turn influence the immune response to the expressed protein. Physical barriers and other factors may impede diffusion of the DNA within the muscle tissue or its entry into the muscle fibres. Although the efficiency of gene transfer in normal mouse muscle is low (< 100 fibres per injection site), a humoral response to the hepatitis B surface antigen (HBsAg) is obtained after expression of a transferred gene. Direct gene transfer is ten times more efficient in regenerating than in normal mouse muscle. DNA-based immunization in such regenerating muscles results in an earlier and stronger humoral response to HBsAg than is seen in normal mature muscle. A needleless jet injection system (Biojector) is able to deliver DNA into normal muscle in rats and rabbits such that a substantial immune response is obtained. PMID- 7879415 TI - Self-replicating Semliki Forest virus RNA as recombinant vaccine. AB - Recombinant RNA based on the Semliki Forest virus (SFV) replicon was used to express the nucleoprotein of influenza virus in mice. Two strategies were employed to deliver the RNA. In the first, recombinant RNA was packaged into infectious suicide SFV particles which were used directly for immunization. The second approach involved injection of in vitro-synthesized RNA directly into the quadriceps muscle. Both approaches resulted in the generation of humoral responses with high antibody titres. Immunization with suicide particles showed that a strong, class I-restricted cytotoxic T-cell response can be obtained using only 100 infectious units. We conclude that the self-replicative recombinant SFV RNA may be quite useful as a nucleic acid vaccine. PMID- 7879416 TI - Regulatory considerations for nucleic acid vaccines. AB - For regulatory purposes nucleic acid vaccines are considered biological products and will be regulated by the Center for Biologics Evaluation and Research (CBER). Vaccines derived through the use of this technology may ultimately find broad application as preventive vaccines for infectious disease or as therapeutic vaccines for treatment of disease. The regulations that govern the use of biological products as well as other guidance documents available from CBER are applicable to the regulation of nucleic acid vaccines. The regulatory concerns associated with the manufacture, preclinical evaluation and clinical studies for these vaccines are similar to those for other biological products. The following discussion will provide an overview of the organization of CBER and how nucleic acid vaccines will be reviewed within this organization. This discussion will also describe the regulations encoded in the US Code of Federal Regulations which govern the use of biological products and additional guidance provided in Points to Consider Documents and in specific Guidelines. In addition, this discussion will note specific concerns regarding the manufacture, lot release and preclinical evaluation to assess the safety of polynucleotide vaccines. Finally, the process for submission of an Investigational New Drug application and the design of protocols for clinical studies will be described. PMID- 7879417 TI - Nucleic acid immunization: a prophylactic gene therapy? AB - Nucleic acid (NA) vaccines may offer the safety of subunit or inactivated vaccines and, at the same time, provide the advantages of live recombinant vaccines, such as induction of a protective cellular immune response. In Germany, the so-called 'Gene Law' regulates the genetic modification of organisms such as prokaryotic or eukaryotic cells for the construction of recombinant NAs intended for use as NA vaccines. Neither NAs nor human beings treated with NAs are subject to Gene Law regulations but preclinical laboratory experiments are regulated by the Gene Law. Gene therapy, as defined in a recent draft of a European guideline for the production of gene therapeutics, includes the genetic modification of human somatic cells via transfer of NAs and thus includes NA vaccines. The guideline provides recommendations for the production of NA vaccines for human use and for preclinical safety testing. NA vaccines are products derived by biotechnological processes, as defined in part A of the annex of Council Regulation (EEC) No. 2309/93 of 22 July 1993. Applications for marketing authorization in Member States of the European Union will thus be reviewed by the European Agency for the Evaluation of Medicinal Products starting from 1 January 1995. Inoculation of NAs encompassing a full-length but int/nef-defective simian immunodeficiency provirus allowing limited replication of viruses released is being investigated at the Paul-Ehrlich-Institute as a model for a NA vaccine against AIDS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879418 TI - Safety considerations for nucleic acid vaccines. AB - Whilst it is premature to formulate guidelines for the manufacturing requirements of a nucleic acid vaccine, it can never be too early to discuss and debate the issues surrounding the use of a novel biotherapeutic. The major safety issues posed by nucleic acid vaccination include the possibility of transformation (or tumorigenic) events in recipients of a DNA vaccine, the potential formation of anti-DNA antibodies, and unexpected and untoward effects of long-term expression of a foreign antigen. This paper examines the extent to which these points impinge on the safety of DNA vaccines. PMID- 7879419 TI - Protection against malaria by immunization with a Plasmodium yoelii circumsporozoite protein nucleic acid vaccine. AB - Nucleic acid vaccines provide an exciting new alternative approach to developing the multiantigen vaccines designed to induce protective antibody and T-cell responses against Plasmodium proteins that many experts believe will be required for effective protection against malaria. As a first step in this process, we produced a plasmid DNA vaccine that includes the gene encoding the P. yoelii circumsporozoite protein (PyCSP). This vaccine induced higher levels of antibodies and cytotoxic T lymphocytes against PyCSP than immunization with irradiated sporozoites, and protected 9 of the first 16 mice immunized. Work is now in progress to optimize immunization regimens, establish the mechanisms of protective immunity induced by the vaccine, and to determine whether protective immunity can be increased by vaccinating with multiple nucleic acid vaccines designed to produce immune responses against multiple targets. PMID- 7879420 TI - Genetic vaccination against leishmaniasis. AB - The gene encoding for a major surface glycoprotein, gp63, of Leishmania major was cloned into the eukaryotic expression plasmid pCDNAI with CMV or RSV promoters. The highly susceptible Balb/c mice were injected intramuscularly with 100 micrograms/mouse of the purified plasmid. The plasmids were found to be stable in vivo for at least 40 days after injection and expressed significant levels of gp63, demonstrable by immunohistological staining with specific antibody. The immunized mice developed significant resistance against L. major infection compared to controls similarly immunized with the empty plasmid. Spleen cells from the immunized mice produced significant levels of IL-2 and IFN-gamma but no detectable IL-4 when cultured with leishmanial antigens in vitro. PMID- 7879421 TI - Towards a DNA vaccine against tuberculosis. AB - Expression of the gene for a single mycobacterial antigen (Mycobacterium leprae hsp65) in adult Balb/c mice resulted in substantial cell-mediated protection against challenge with M. tuberculosis. CD4 and CD8 T cells cloned from spleens of such immunized mice passively transferred protection to non-immunized mice, and CD8 cells selectively lysed macrophages infected with M. tuberculosis. Three modes of expressing the gene have been tested: (1) expression from a retroviral vector (pZIPNeoSV) in implanted J774 tumour cells, (2) expression from the same vector via bone marrow cells transfected in vitro and used to reconstitute irradiated mice, and (3) in a preliminary experiment, from CMV immediate-early and hydroxymethylglutaryl Co-A reductase promoters injected as plasmid DNA into muscle. PMID- 7879422 TI - Protective immunity by intramuscular injection of low doses of influenza virus DNA vaccines. AB - Dose-response relationships were investigated between dose of influenza virus haemagglutinin (HA) or nucleoprotein (NP) DNA vaccines, and immunogenicity and protective efficacy based on humoral and cellular immunity. In mice, intramuscular (i.m.) injection of HA or NP DNA, at doses of 100 ng to 1 microgram, was found to generate haemagglutination inhibiting (HI) antibodies and cytotoxic T-lymphocytes, respectively, and provide protection in influenza virus challenge models. A direct correlation between the amount of DNA injected and the level of HI antibody was observed. In non-human primates, high-titre neutralizing antibodies were induced in animals vaccinated with as little as 10 micrograms of HA DNA. These results indicate that low doses of DNA administered by i.m. injection provide protective efficacy against influenza. PMID- 7879423 TI - Facilitated DNA inoculation induces anti-HIV-1 immunity in vivo. AB - Vaccine design against HIV-1 is complicated both by the latent aspects of lentiviral infection and the diversity of the virus. The type of vaccine approach used is therefore likely to be critically important. In general, vaccination strategies have relied on the use of live attenuated material or inactivated/subunit preparations as specific immunogens. Each of these methodologies has advantages and disadvantages in terms of the elicitation of broad cellular and humoral immune responses. Although most success has been achieved with live attenuated vaccines, there is a conceptual safety concern associated with the use of these vaccines for the prevention of human infections. In contrast, subunit or killed vaccine preparations enjoy advantages in preparation and conceptual safety; however, their ability to elicit broad immunity is more limited. In theory, inoculation of a plasmid DNA that supports in vivo expression of proteins, and therefore presentation of the processed protein antigen to the immune system, could be used to combine the features of a subunit vaccine and a live attenuated vaccine. We have designed a strategy for intramuscular DNA inoculation to elicit humoral and cellular immune responses against expressed HIV antigens. Uptake and expression are significantly enhanced if DNA is administered in conjunction with the facilitating agent bupivacaine HCl. Using this technique we have demonstrated functional cellular and humoral immune responses against the majority of HIV-1 encoded antigens in both rodents and non-human primates. PMID- 7879424 TI - [Protein-synthesis blockers reproduce the effect of nociceptive sensitization on the defense and food reactions in the snail]. AB - Effects of translation inhibitors on defence and feeding behaviour and command neurons of defence behaviour (L-RPl1) were studied in Helix lucorum snail. It was found that anisomycin and cycloheximide facilitated defence reactions and neuronal responses evoked by tactile or chemical stimuli 60-80 min after inhibitor application. At the same time feeding behaviour and neuronal responses (L-RMtc1 neurons) evoked by a food stimulus were suppressed. Effects of inhibitors were obtained within 30 min of their application or single injection in intact snail. Effects of inhibitors were absent after continuous application or double injection with 50 min interval. Duration of the inhibitor effects depended on modality of a sensory stimulus. In particular, inhibitor effects on behavioural and neuronal responses evoked by tactile stimuli lasted 1 h., by weak quinine solution--2-3 h., and by a food stimulus--1.5 h. Cycloheximide suppressed only appetitive phase of feeding behaviour but did not affect consummatory phase of feeding behavior. Some parameters of the behavioural and neuronal effects were similar to those obtained during sensitization development. It was suggested that translation inhibitors induced activation of synthesis of protein molecules with a short lifetime, functions of which consisted in selective regulation of synaptic transmission. PMID- 7879425 TI - [The pharmacological testing of intracortical interneuronal connections]. AB - An attempt is made to study the influence of acetylcholine on functional connections of cortical neurons and their frequency characteristics. Multiunit activity was recorded in the sensorimotor cortex of immobilized and freely moving rats. Crosscorrelation analysis was used. Influence of acetylcholine (Ach) and Ca chelator ethyleneglicoltetraacetat (EGTA) on the functional characteristics of the neighbouring neurons was studied in the first series of experiments. The substances were iontophoretically applied to the sensorimotor cortex neurons of the immobilized unanesthetized rats. Application of Ach led to variation in the frequency characteristics of single neurons and in the majority cases did not affect the neuronal interrelations. EGTA application, independently on the background frequency of the neuronal activity, resulted in disappearance of interneuronal connections which recovered after the end of EGTA effect. The second series of experiments was carried out in freely moving rats. System injection of galantamine essentially increased the frequency of activity of the cortical neurons not affecting their network activity. We suppose that intracortical relations can be realized independently on the extracortical influences which are manifested in variations in the background impulsation of the single neurons. Qualitative estimation of Ach influence on the functional characteristics of the cortical neurons do not reveal Ach effects on formation of intracortical connections. The technique used by us may be applied in further studies of intracortical neurons connections. PMID- 7879426 TI - [The modulation by cholinergic substances of the influences of cortical input on hippocampal neurons]. AB - Cholinergic modulation of the single-cell responses and field potentials evoked in the hippocampus by electrical stimulation of its cortical input was investigated in two groups of chronic anaesthetized rabbits--with the intact septum (IS) and basally undercut (BS). In both groups of animals responses to stimulation of the perforant path (PP) or mossy fibers were blocked or significantly suppressed in substantial proportion of the neurons (50% in IS, 69% in BS) by i.v. physostigmine injection; facilitation of responses was observed in minor groups of the neurons (10% and 8%). Scopolamine restored initial responsiveness of the hippocampal neurons and augmented responses to stimulation in some of them (37.5% in IS, 65% in BS). Effect of physostigmine was reproduced by single stimuli applied to the MS--DB. Field potentials evoked by PP stimulation in CA of IS group were equally suppressed (by 43%) by the sensory stimulation evoking natural theta, by physostigmine and MS--DB stimulation. In BS group of animals these influences completely suppressed the focal potentials to PP stimulation. Scopolamine restored the focal potentials. It is concluded that the main function of the septo-hippocampal cholinergic input consists in filtering out the signals appearing at the background of the theta-rhythm triggered by a previous signal thus preventing their interference with its processing and recording. PMID- 7879427 TI - [The phasic relations between the rhythmic activities of the rabbit cortical structures at different frequencies of stimulation of the midbrain reticular formation]. AB - Phase shifts between the rhythmical activity of the hippocampus (CA1), somatosensory, motor and visual areas of the neocortex in the delta-, theta- and alpha-bands were studied during electrostimulation of the mesencephalic reticular formation with different frequencies. It was found that increasing stimulation frequency resulted in nonlinear decrease of the phase shifts in the theta-band between recordings which included the visual cortical area, and increase of the phase shifts between the theta-rhythm, recorded in the hippocampus, somatosensory and motor cortical areas. In the delta-band increase of the phase shifts was observed only in the pairs of recordings from the last-mentioned group of structures at stimulation frequencies more than 200 1/sec. Phase shifts in the alpha-rhythm between the cortical recordings varied at different stimulation frequencies. Reliable changes of the alpha-rhythm phase shifts were observed during stimulation with the frequency 60-200 1/sec between recordings from the hippocampus, motor and somatosensory areas, and at 500-700 1/sec--in the pairs of recordings which included the visual cortical area. PMID- 7879428 TI - [Inhibitory interactions in neuronal networks including cells of the auditory cortex and the medial geniculate body]. AB - Cross-correlation method was used for revealing effective inhibitory interactions in neural networks containing simultaneously recorded neurons from different loci of auditory cortex (A1) and medial geniculate body (MGB). It was shown that (i) inhibitory connections were "divergent", i. e., one neuron in A1 (MGB) depressed activity of neurons in different loci of A1 and MGB simultaneously; (ii) inputs to inhibitory neuron were "convergent", i.e., one neuron in A1 (MGB) was excited by neurons from different loci of A1 and MGB simultaneously. There were inhibitory neurons which selectively depressed activity of only one neighbouring neuron. The results allow to suggest that the same inhibitory neuron may be involved in afferent and feedback inhibition. We supposed that the principles of organization of inhibitory connections in thalamo-cortical networks underlie the observed exceptions to mapping (tonotopic) principle of organization of receptive fields of A1 and MGB. PMID- 7879429 TI - [The perceptive color space in the carp (Carpio cyprinus L.)]. AB - Discrimination of colours was studied using choice conditioning paradigm (one of a pair of colour stimuli) in carps. Matrix of probabilities of instrumental reactions (catching a bead) was constructed by the results of eight experimental sessions with successive reinforcement of one of the eight colours. It was processed by factor analysis. The spherical structure of carp's perceptual colour space revealed by factor analysis was similar to that of monkeys and humans. Four eigenvectors which constituted four-dimensional Euclidean hypersphere corresponded to excitation of four colour-encoding neuronal channels, i.e., red green, blue-yellow, bright and dark. PMID- 7879430 TI - [G-protein activators enhance the plasticity of the cholinoreceptors of snail neurons]. AB - Influence of two G-protein activators 5-guanylylimidodiphosphate (Gpp(NH)p) and guanosine 5'-O-(3-thiotriphosphate (GTP-gamma-S) on extinction of inward current evoked by local acethylcholine application (Ach-current) on the neurons RPa3 and LPa3 of Helix lucorum was studied using two-electrode voltage clamp technique. Non-reversible deepening of Ach-current extinction after intracellular injections (-2 nA, 10 min) of Gpp(NH)p and GTP-gamma-S was shown. A conclusion was made on participation of G-proteins in regulatory molecular mechanism of cholinoreceptor plasticity. Both activators of G-proteins demonstrated a novel unusual action on Ach-current extinction. They disturbed monotonous course of extinction. Oscillations of intracellular concentration of calcium ions are supposed to be the reason of such an effect. PMID- 7879431 TI - [Structural changes and reorganization of the activity of the cortical neurons in the behavior of chronically alcoholized rabbits]. AB - Unit activity in the limbic cortex recorded during food acquisition behaviour was analyzed in the rabbits that were subjected to chronic (2.5-3.0 months) alcohol administration (CA). Morphological changes in the limbic cortex were studied in the same animals. It was shown that after CA the numerical density of cell bodies decreased as compared to that of the healthy animals and the size of cell bodies changed; number of units, activity of which could be detected during microelectrode penetration, decreased as well. All aforementioned changes were more prominent in the upper (II-IV) layers of the cortex as compared to the lower (V-VI) ones. These facts are associated with the decrease of the number of active units belonging to systems formed in the later phases of individual development. There was no decrease of the number of active units following an acute administration of alcohol in the chronic animals unlike the situation observed in the healthy animals. PMID- 7879432 TI - [The brain electrical processes in dominant alcoholic motivation in rats]. AB - Electrical activity of the cerebral cortex and lateral hypothalamus was recorded in 2 groups of alcoholized rats 1) in motivation state induced by one-day alcohol deprivation and 2) after long-lasting free consumption of alcohol. Non alcoholized rats served as the control. Neocortical and hypothalamic EEG in non deprived rats with pronounced attraction to alcohol consumption did not differ from the control. Power spectra of this activity had the peaks in the delta band. The amplitude of the delta rhythm in the cortex was twice as high as that in the hypothalamus. During alcohol deprivation power spectra of the neocortical and hypothalamic EEG were alike, and in most of the cases spectral density in the hypothalamus (with the delta peak) exceeded the cortical one. Termination of the alcohol deprivation by ethanol injection per rectum induced in some animals reversible spectral changes in the hypothalamic EEG and well-pronounced shift of its peak towards the theta rhythm. PMID- 7879433 TI - [The sensorimotor reactivity of rats with an initially high anxiety-phobia level]. AB - Sensorimotor response was measured by acoustic startle reflex in Wistar male rats with innate high and low levels of anxiety. The levels of anxiety were determined using a complex multiparameter method for evaluating anxiety-phobic states in rats by a ranged scale. Amplitude and prepulse inhibition of the acoustic startle response were increased, but latency of the startle reflex was decreased in rats with innate high level of anxiety as compared with those with innate low level. In rats with innate high level of anxiety injection of subconvulsive doses of pentylenetetrazol (10 and 15 mg/kg i.p.) resulted in an increase of the amplitude of the acoustic startle response and, additionally (under the dose 10 mg/kg) in a decrease of its latency. Facilitation of acoustic startle in rats with innate high level of anxiety is suggested to reflect either a deficit of inhibitory, or intensification of excitatory modulating influences on signal transmission in nerve circuit of acoustic startle. Studies of the sensorimotor response by acoustic startle in rats with innate high level of anxiety are believed to be useful for elucidating basic mechanisms of anxiety and phobia. PMID- 7879434 TI - [The correlation of stress and neurosis vulnerability in the structure of nonspecific resistance to extreme factors in intact and pregnant rats]. AB - White male rats, intact and pregnant females were subjected for 3 days to deprivation of paradoxical sleep by the technique of Jouvet. The main resulting vectors of the extreme state outcome, i.e., lethality, susceptibility to stress, and neurotization, made it possible to establish corresponding levels of resistance. A relationship of each of the levels with the ability to form conditioned reflexes, initial functional interhemispheric asymmetry and behavioural status, expression of protective reactions and paradoxical sleep under conditions of an insoluble conflict situation was followed. High resistance of pregnant rats is considered to be associated with the formation of gestational ambilaterality of the brain of intact animals. Such an increase in resistance is selective as far as it concerns the organism of the pregnant and it does not ensure stability of the feto-maternal complex under extreme conditions. It was established that there was an inverse relationship between the expression of neurotic disorders of the higher nervous activity and vegeto-morphological features of acute stress. This gives reason to define more exactly the role of neurotic disorders in the pathogenesis of stress and mechanisms of resistance to extreme factors. PMID- 7879435 TI - [The neurochemical mechanisms of the central amygdaloid nucleus and the anxiolytic action of tranquilizers in different models of anxiety states]. AB - Chemical stimulation of the central nucleus of the amygdalar complex was carried out in rats during performance of tests of avoidance of "lighted square" and "threatening situation". Microinjections of monoamines, GABA, glutamate, some of their receptor agonists and antagonists revealed neurochemical heterogeneity of the structure and functional ambiguity of neurotransmitter systems in genesis of anxiety of different aversive modes. Chlordiazepoxid, phenibut, indoter, campiron, campironin decrease anxiety in the tests of avoidance of "lighted square" and "threatening situation", their effects being similar to those of dopamine, GABA, or serotonin. A conclusion is made that distinctions in spectra of anxiosedative and anxioselective drugs under study may be caused by unequal contribution of monoamine and amino acid transmitter mechanisms of the central region of the amygdalar complex in genesis of heteromodal aversive anxiety. PMID- 7879436 TI - [Lysergic acid diethylamide blockade of the brain serotoninergic receptors prevents the facilitating effect of phenamine on self-stimulation in rats with destruction of the medial prefrontal cortex]. AB - Amphetamine (1 mg/kg) increased the rate of pedal self-stimulation of the lateral hypothalamus of Wistar rats in Skinner box by 37%. Lesion of the medial prefrontal cortex with kainic acid (16 mcg/kg in 8 mcl) 10-14 days prior to the experiment did not prevent facilitating effect of amphetamine on self stimulation. Lysergic acid diethylamid (10 mcg/kg) did not influence self stimulation response in rats with damaged medial prefrontal cortex, but after its preliminary administration prevented the stimulating effect of amphetamine on self-stimulation of the lateral hypothalamus. The findings are discussed from two points of view: 1) the phenomenon observed is associated with the existence of hypothalamic autoregulatory dopaminergic system which provides realization of self-stimulation; 2) modulating influence of the medial prefrontal cortex on the lateral hypothalamus is mediated not only by dopaminergic but also by serotoninergic axons. It is suggested that both mechanisms may underlie the phenomenon under study. PMID- 7879437 TI - [Sex differences in the dynamic interhemispheric asymmetry of the cortical regulation of pain vocalizations in rats]. PMID- 7879438 TI - [Disordered reproductive function in rats genetically selected for their capacity for active avoidance]. PMID- 7879439 TI - [Changes in the cytophotometric and morphometric characteristics of the skin receptors in low- and high-excitable rats after different times following the conclusion of a neurotization exposure]. PMID- 7879440 TI - [The sensitive period of imprinting in wild and domestic goslings]. PMID- 7879441 TI - [Changes in the impulse activity of Retzius' neuron in the leech during synaptic activation at different frequencies]. PMID- 7879442 TI - [The subjective evaluation of time intervals by 3- to 6-year-old children]. AB - The investigation of 3-6 aged children's time perception shows that subjective scaling methods, which except the direct magnitude estimates (cross-modality matching, categorization and duration production) reveal the reliable results. These methods may be used for the age, when the "conceptual time" (the concepts of physical time units) has not be developed yet. PMID- 7879443 TI - [Consciousness: what is it? The plenum of the Scientific Council of the Svetloe Piatno International Research Center on the Neurobiology of Consciousness, Moscow, 24-27 May 1994]. PMID- 7879444 TI - [Pivotal problems in the psychophysiology of consciousness]. AB - The key point in the psychophysiological study of consciousness is the problem of finding out qualitative differences in reactions (event-related potentials) on recognized and unrecognized verbal and nonverbal stimuli. The role of the neural mechanisms of focused attention and the functional hemispheric asymmetry in neurobiology of consciousness is discussed. PMID- 7879445 TI - [Synchronization and cooperative interaction in brain activities]. AB - A review. A concept is suggested according to which synchronization and cooperative interaction of plastic processes, taking place both at the level of a separate cell and at the level of cellular ensembles of different degree of complication form brain principle of integration. The induction and development of plastic processes, in which motivational-emotional structures take part, are realized via the mechanism of cellular excitability change. The influences of these structures are widely spread over the cortex, but are selective in accordance with the current organism need. PMID- 7879446 TI - [The spatial ordering of the brain electrical processes as an index of its functional organization]. AB - Analysis of constraints, which are imposed on correctness of conclusions drawn from the studies of the spectrum-correlation model of cortex electrical activity, and necessity of enlarging interaction forms which have to be studied, brought to development a new index for estimating spatial order of cortex electrical processes. This index and the technique were called "multiple entropy" (ME). The algorithm of calculating ME and its properties are discussed. The results of studying spatial structure of cortex electrical processes by estimating their spatial synchronization and ME were compared. It was shown that these approaches complemented each other. Using both these techniques in combination gives more complete picture of integration of cortex processes. PMID- 7879447 TI - [Heart rhythm indices during human solving of arithmetic tasks]. AB - Heart rate and respiration were recorded in a group of 90 subjects (25 males and 65 females) aged 17-19 during rest and under informational load (arithmetical tasks) lasting 3 min each. Off-line spectral analysis was performed for all the subjects. Anxiety according to Spilberger and strength of excitation-inhibition according to Strelau were also tested. It was shown that heart rate increased significantly in the group as a whole, however, variability of RR-intervals remained unchanged. Then two subgroups of subjects who responded to information load by a decrease and increase of RR-interval variability were distinguished. These subgroups were characterized respectively by the high and low levels of personal anxiety. The decrease of RR-interval variability in the high-anxiety subgroup was associated with a decrease of power in all frequency bands of the rate spectrum. The increase of RR-interval variability in the low-anxiety subground was due to an increase of heart rate modulation in a low-frequency band of the heart rate spectrum. Fatigue is regarded as a cause of such heart rate modulation. PMID- 7879449 TI - [The frontal-motor interneuronal interactions in cats realizing a free choice of reinforcement]. AB - Instrumental delayed reflexes with reinforcement of different quality were elaborated in six cats by the method of "active choice", where the time of delay of the motor reaction served as a signal of quality of the reinforcement. Individually varying ability to choose the quality of the reinforcement was used for classification of typological features of cats (self-control and impulsiveness). Multiunit activity was recorded by nichrome semimicroelectrodes from the frontal and motor cortical areas. Crosscorrelation analysis of interneuronal connections was carried out. The interneuronal frontal-motor relationships with different temporal delays (0-30; 30-60; 60-100 ms) were equally manifested in both groups of cats. We suggested that the organization of the frontal-motor relations did not characterize the individual typological features of the cats. During short-delayed reflexes in cats of both groups the identified functional connections with delays 0-30 ms were more significant. The question is discussed on the role of the frontal-motor coordination in definition of the kind of behaviour of cats to fulfil either short- or long-delayed conditioned reactions. PMID- 7879448 TI - [The characteristics of the memory retention of a tactile-kinesthetic image in preschool children]. AB - Peculiarities of voluntary control of tactile-kinesthetic memorizing were studied in children under school age. No sex differences were revealed in retention of the images in children aged 4-5. Girls at the age of 5-6 showed a remarkable growth of memorizing capacity in comparison with boys of the same age. Thus, the age of 5-6 may be considered as a critical period for developing voluntary memory in girls but not in boys. PMID- 7879450 TI - [The mechanisms of the formation of neuronal reactions in the cat motor cortex related to the initiation of a conditioned reflex of the placing of a limb on a support: hypothesis]. AB - Excitatory reactions of the motor cortex neurons during initiation of the conditioned placing are supposed to be based on NMDA receptor activation. The conditions needed for the NMDA receptor-driven channels to be opened by glutamate (mainly, postsynaptic hyperpolarization neutralization), are provided by the conditioned "arousal reaction" through the augmentation of cholinergic/noradrenergic bombardment of the motor cortex neurons. PMID- 7879451 TI - [The effect of the immunomodulator neurotropin on the learning of active defensive behavior by rats]. AB - Rats were intraperitoneally injected with neurotropin (NSP), a substrate extracted from the inflammatory dermis of rabbits inoculated with Vaccine virus. Active avoidance behaviour of rats was studied. After NSP administration rats demonstrated higher levels of conditioning and true responses compared with control. In NSP-treated rats relationship between the time of beginning of intersignal run during learning and success of the avoidance trial differed from that in the control group. The results suggest that neurotropin administration activates the retrieval processes and leads to stronger consolidation of avoidance behaviour. PMID- 7879452 TI - [The effect of intraspecies isolation in adulthood on the formation of a manipulatory habit in rats]. AB - Dynamics of manipulatory habit formation was examined in white mixed-bred male rats housed in groups or isolated from community at the age of 2 months. A month later all the animals learned to reach food in a horizontal tube using a forepaw. It was shown that the social isolation of adult animals led to slowing the motor habit formation. The effect of isolation depended on paw preference of the animal, i.e., learning was the most difficult for sinistrals and ambidextrals, while the difference between dextral isolants and grouped rats was not significant. The authors consider shown disruptions to be the result of increased negative emotionality of late isolants rather than consequence of their motor disability. PMID- 7879453 TI - [The advanced display of behavioral reactions in sensory deprived rat pups]. AB - Bilateral section of nervus medianus was made in Wistar rat pups on 13, 14, 15 or 16-th days of life. Developmental analysis of motor abilities, locomotor and exploration activities during 10-30 days of life revealed three groups of facts. 1. Partial deafferentation of forelimbs don't influence on some types of behavior. 2. Some motor abilities hindered in rat pups with section of nervus medianus. 3. Partial deafferentation of forelimb gives rise to the faster appearance of the new types of behavior. The developmental analysis allowed to suggest that faster appearance of certain behavior reactions after deafferentation of the forelimbs is a result of actualization of latent sensory inputs including in the organization of these types of behavior but it is not connected with changing of velocity of morphological maturation. PMID- 7879454 TI - [A delay in the development of hearing and a shift in the leading afferentation in the early behavioral ontogeny of birds]. AB - Development of auditory sensitivity was studied by recording microphonic component of cochlear potentials during the period of opening the eyes in 6 species of birds with different types of ontogeny (Anas plathyrynchos, Larus canus and L. argentatus, Sterna paradisaea, Coloeus monedula and Corvus frugeleus). The onset of opening the eyes is accompanied by a delay in development of auditory sensitivity and temporary decrease of upper frequency limit of the audible range. Before such a delay acoustic afferentation is leading in feeding behaviour or in response of following in nestlings or chicks. After the period of delay pure tones lose the efficacy in eliciting feeding and following reactions, and the correlation between the low-frequency range of increased sensitivity and the efficacy of pure tone signals disappears, while the new peak of sensitivity appears which fits the maximal energetic component of the parental acoustic signals. It seems possible that the delay may be the result of brain temperature decrease while eyes open the thermoregulation being unstable. Such a delay may facilitate also the substitution of acoustic afferentation for visual in the main behavioural responses in early ontogeny. PMID- 7879455 TI - [Epidemiological indications for the etiology of proteinuria, hypertension in pregnancy and pre-eclampsia--a longitudinal cohort studies of all Swedish women giving birth between 1973 and 1981 to 3 singleton infants]. AB - Based on centrally recorded data about all pregnancies that led to delivery in Sweden in the years from 1973 to 1981 this longitudinal study considers the course of pregnancies of all women who gave birth to their first three single babies during observation time especially regarding hypertension, proteinuria, pre-eclampsia and eclampsia-here subsumized under HP-disease. Incidence of HP disease is shown to be 8.1% of all observed women, depending on the theoretical approach at a minimum of 34% and a maximum of 44% being due to primary, pregnancy induced HP-disease. Some epidemiologic findings may give some hints on the etiology of HP-disease: In primary HP-disease mother's age is in the normal range, whereas infection of the urinary tract, diabetes mellitus, fetal deformity are found more frequently. Female fetus are over-represented with existence of HP disease. The influence of HP-disease presence and parity on fetal development and fetal outcome are discussed. PMID- 7879456 TI - [Cholesterol, HDL-cholesterol, triglycerides and beta-lipoprotein in diabetic pregnancy]. AB - Follow up studies regarding lipid metabolism in diabetic pregnancy are important in maternal and fetal morbidity. OBJECTIVE: With this background it is particularly opportune to consider the difference of cholesterol, triglycerides and HDL-cholesterol of diabetics and nondiabetics in pregnancy. In addition the correlation of lipids to the glycosylated hemoglobin (HbA1), White groups and other clinical parameters is of interest. Attention is given to the comparison of insulin dependent diabetics (IDDM) and gestational diabetes (GDM) in the 3rd trimester. PATIENTS: A diabetic group of 84 patients (IDDM, GDM) was used for the prospective study over a two years period. The lipid metabolism was estimated preconceptionally, during pregnancy and on 7th day after delivery. 36 pregnant healthy women served as controls. The information obtained from each patient was entered into an SPSS data base. Statistical analysis were done by Mann-Whitney U and Kruskall-Wallis test and by means of Pearson's correlation coefficient to correlate with age, parity, body mass index, creatinin, albumiuria, HbA1, blood pressure. RESULTS: There were no any correlations between lipid parameters cholesterol, triglycerides, HDL-C, beta-lipoprotein and HbA1 as well as White groups (Pearson's coefficient). The triglyceride levels were significant lower in diabetic pregnants compared with healthy controls (p = 0.0095; Wilcoxon Test); diabetes: mean = 1,831 mmol/l; min 0.35; max 5.99 and control group mean = 2,133 mmol/l; min 0.36; max 4.70. Cholesterol levels were higher in the 3rd trimester of GDM patients than values of IDDM's (p = 0.0017; Wilcoxon Test). The longitudinal study during diabetic pregnancy resulted in significantly progressive increase in cholesterol and triglyceride levels (p = 0.0035 bzw. p = 0.0099; Kruskal-Wallis Test). CONCLUSIONS: Significant lower triglyceride levels had been found in diabetic pregnants than in healthy controls. There was no any correlation between lipid parameters cholesterol, triglycerides, HDL-cholesterol, beta-lipoprotein on the one side and HbA1 and White groups on the other side. Increased cholesterol levels were noted in the 3rd trimester of pregnancy in the gestational diabetes in comparison of insulin dependent pregnant diabetics. PMID- 7879457 TI - [Effect of trapidil in prevention of pre-eclampsia and fetal retardation]. AB - Pre-eclampsia is suggested to be characterized by a functional imbalance between vascular prostacyclin and thromboxane A2 production. On the basis of this hypothesis it is attempted to correct this pathologic conditions by pharmacological manipulation with Trapidil, a triazolo pyrimidin derivative, because of its effects on the prostanoid metabolism. A prospective, randomized, double blind, placebo-controlled study was carried out to investigate Trapidil in the prevention of pregnancy-induced hypertension or pre-eclampsia. A total of 160 pregnant women with the risk to develop pre-eclampsia received Trapidil or placebo between week 24 and 38 of gestation. The number of patients in whom pregnancy-induced hypertension or pre-eclampsia developed was significantly lower in the Trapidil-treated (5.5%) compared with the placebo-treated group (14.1%). Additionally, a reduced risk of preterm deliveries and severe fetal growth retardation could be observed. In 7 patients with manifest pre-eclampsia or pregnancy-induced hypertension the circulating eicosanoid concentrations were determined before and during Trapidil medication. Trapidil was associated with an about twofold increase of 6-keto PGF1 alpha concentration in the peripheral venous blood, while the concentration of thromboxane A2 revealed no changes. PMID- 7879458 TI - [First sexual intercourse in women]. AB - Out of a group of 700 Czech girls aged 16 to 18 years questioned by means of interviews 344 (49.1%) already had their first heterosexual coitus. Thirty-three of them reached orgasm during their first sexual intercourse and during second and further intercourses they were orgasmic mostly or always. The second subgroup comprised 32 girls who were anorgasmic not only during their first sexual intercourse but also during their further sexual life. Statistically significant differences between these two subgroups were found in the following items: Orgasmic girls were more frequently longing for their first sexual intercourse whereas of the anorgasmic girls the motives were curiosity or the effort to satisfy their partners. The majority of these girls experienced the first sexual intercourse as unpleasant and reported frequent occurrence of bleeding. Furthermore, they had to regret more frequently the loss of their fathers during the first 6 years of their lives than the girls of the first subgroup had. PMID- 7879459 TI - [The role of immunologic factors in the etiology of pregnancy-induced hypertension]. AB - Pregnancy-induced hypertension (PIH) is a placental disease that mainly occurs in primigravidae, but its precise etiology is not yet known. It has long been considered that the protective effect of multiparity may be due to immunological factors. Here, we review epidemiologic data from the literature supporting the idea of a possible immunological basis of PIH. There are conflicting reports in the literature regarding the involvement of cellular and humoral mechanisms in the etiology of PIH, the impact of histocompatibility and the interactions between maternal and fetal genotype. Finally, the evidence for a common immunologic cause for pregnancy-induced hypertension and miscarriage is discussed. PMID- 7879460 TI - [The early pregnancy factor (EPF) as an early marker of disorders in pregnancy]. AB - The early pregnancy factor (EPF) seems to be very helpful in clinical applications such as early detection of pregnancy, differential diagnosis of failure of fertilization or implementation and prognosis of a fertilized ovum. Our purpose was to investigate the diagnostic value of single and serial measurement of EPF, especially in the differential diagnosis of abortion and extrauterine pregnancy. Women with a history of 6-16 weeks amenorrhoea with/without vaginal bleeding were included in the prospective study. The EPF test system was carried out by means of the rosette inhibition method. EPF proved to be always positive in normal pregnant women and always negative in nonpregnant controls. In case of threatened abortion the prognosis was good, when the EPF values were positive, and poor when they became negative. Patients suffering from spontaneous and missed abortion mostly showed negative EPF-values. This was also true in ectopic pregnancies. The sensitivity and specificity of EPF-test system were 83%. The positive predictive value was observed to be 54% and the negative predictive value 95%. The EPF as an early embryonic signal may be a suitable parameter for the clinical use detecting pregnancy disturbances very early. PMID- 7879461 TI - [Uterine reactions to prostaglandins in induced labor--results of a multicenter study]. AB - During a prospective multicentric study concerning labor induction with prostaglandins 1472 prostaglandin-inductions were documented. With a Bishop Score < 5 a gel containing 0.5 mg of PgE2 was applied intracervically, with a Bishop Score > = 5 a tablet containing 3 mg of PgE2 was applied retrocervically inside vagina. In case of lacking success the application was repeated after 6 to 8 hours and after 24 hours according to the actual Bishop-Score. Coordinated labor after application of PG-gel or PG-tablet was observed in 85.2% (83.3% respectively), polycystolia or tetani in 13.9% of cases (9.1% respectively). Differences were not statistically significant. Uterine reactions started in the mean 5-6 hours after the last PG-application, but intervals showed a significant spreading among single cases. In 16.0% of the patients successfully treated with Pg-gel and in 8.3% of the patients successfully treated with a PG-tablet due to a uterine hyperstimulation a tocolytic treatment became necessary. With a ripe cervical score (Bishop-Score > 7 points) a significant shortening of the induction-interval was observed. PMID- 7879462 TI - [Modified Sarafoff suture for single layer closure of uterotomy in cesarean section. A prospective study]. AB - 125 caesarean sections were performed at the Department of Obstetrics and Gynecology, Allgemeines Krankenhaus Celle, during the last 6 months of 1991. The caesarean section rate was 13.4% (930 deliveries in that period).--For closure of the uterotomy a two-layer suture was applied (62 patients) as well as a one-layer suture, the modified Sarafoff suture (63 patients). Both techniques were used alternatively. We compared intraoperative and postoperative courses of the two groups of patients in a prospective study. Between the 8th and 10th day after surgery an ultrasonic examination of the scar was performed. The data in both groups did not show any significant difference, except that the scar in the one layer group was thinner.--So, our results did not support an advantage of the one layer suture as compared to the two-layer technique. PMID- 7879463 TI - [Effects of new dental amalgam fillings in pregnancy on Hg concentration in mother and child. With consideration for possible interactions between amalgam and precious metals]. AB - Amalgam-tooth fillings are suspected to be cause of many different diseases. With special consideration of the problem of newly made fillings, blood samples were taken from 45 affected pregnant women. After birth, newborns and placenta tissue were tested for Hg-contamination. One hundred and twenty one women with older amalgam-fillings were compared to 19 women without amalgam-fillings. The surfaces of the amalgam-fillings were measured in each case in mm2. In 58 women the tooth fillings contained additional precious metal. While in the placentas a retaining function were found of up to ten times higher Hg-values but low correlations to the amalgam surfaces, the Hg-concentrations in the blood samples of mother and child did not correlate to the amalgam-fillings. Newly made fillings during pregnancy had no influence on the Hg-concentration, neither had the contact to precious metals in the approximal and the antagonistic range. The wide-spreading of Hg-values without correlation to the filling-surfaces speaks for a great influence of other environmental factors. PMID- 7879464 TI - [Uterine rupture without predisposing factors after a single vaginal PgE2 administration in prolonged pregnancy]. AB - The case of a 38-year old 3/1 gravida with prolonged pregnancy is discussed. Labour was induced with a prostaglandin (PgE2-) vaginal tablet 4 days after an oxytocin stress test had failed. After rapid labour development, imminent fetal asphyxia suddenly occurred, leading to an emergency cesarean section. A rupture of the left uterus wall rupture with laceration of uterine vessels was demonstrated. This is the first case report of a uterus rupture that happened in prolonged pregnancy without predisposing risk factors after a single PgE2 dose that was correctly placed into the posterior fornix. PMID- 7879465 TI - [Urine phlegmon--a rare complication after laparoscopic tubal sterilization]. AB - A case of an extraperitoneal injury of the urinary bladder by an endoscopical sterilization of the fallopian tubes is reported. The occurrence of clinical symptoms in a temporary difference to operation makes diagnosis of this rare complication difficult. PMID- 7879466 TI - [The heterogeneity of Streptococcus pyogenes strains isolated from clinically healthy and sick children in an organized collective]. AB - Experiments on typed strains used as an example revealed that kinetic curves obtained in the lysis by endo-N-aretylmuramidase of virulent strains greatly differed from those obtained from nonvirulent ones: the lysis rate of M+ variants was less than that of M- variants; M- strains gave rather steep kinetic curves of lysis, while those of M+ strains were more declivous. In this study group A S. pyogenes cultures isolated from healthy and sick children in a summer camp were used. The study revealed that cultures, newly isolated from healthy and sick children, were heterogeneous with respect to the M+ and M- state of group A S. pyogenes strains, the amino acid composition of pepsin fragments of M-proteins in the cultures of streptococcus M 1 under study being also heterogeneous. PMID- 7879467 TI - [The epidemiological and epizootiological aspects of listeriosis]. PMID- 7879468 TI - [The intoxication syndrome in infectious pathology: a new look at an old problem]. PMID- 7879469 TI - [The continuous-flow cultivation of gene-engineered strains of microorganisms]. PMID- 7879470 TI - [The goals, tasks and practical realization of a methodology for mass immunological examinations]. PMID- 7879471 TI - [Experience in organizing medical care for the population under the conditions of an extreme situation]. PMID- 7879472 TI - [The role of the Russian Academy of Medical Sciences in the development of Soviet epidemiology]. PMID- 7879473 TI - [The effect of SolcoTrichovac on the vaginal microflora of patients with a papillomavirus infection associated with a cervical intraepithelial neoplasm]. AB - The microbiological study of vaginal secretions of 39 female patients of reproductive age (20-30 years) with papilloma virus infection associated with cervical intraepithelial neoplasia (CIN) was carried out. Of these patients, 28 with papilloma virus infection associated with CINI-II made up group I and II having this infection associated with CINII made up group 2. Dysbiotic disturbances in vaginal bacterial flora, found in these patients, were manifested by a decrease in the isolation rate and number of the lacto- and bifidobacteria simultaneously with the excessive growth of opportunistic bacteria. The results of the oral administration of Solco-Trichovac are indicative of the effectiveness of this preparation, which was confirmed by the data of clinical and bacteriological studies. Together with an increase in the isolation rate of lacto and bifidobacteria, the level of the contamination of the cervicovaginal niche with opportunistic and pathogenic bacterial strains decreased. The results thus obtained make it possible to recommend Solco-Trichovac for the complex treatment of with papilloma virus infection associated with CIN. PMID- 7879474 TI - [The screening and restriction analysis of the plasmid DNA of Salmonella enteritidis strains]. AB - The screening and restriction analysis of plasmid DNA of 36 S. enteritidis strains, isolated in Moscow and Novomoskovsk (Tula Province) at the periods of outbreaks and sporadic diseases, have been made. The possibility of using plasmid screening as an additional method for the differentiation of S. enteritidis strains belonging to different sources of infection has been shown. The restriction analysis has confirmed the conservative character of the nucleotide sequence of the virulence plasmid with a molecular weight of 38 MD, which makes it difficult to use this method for epidemiological purposes. PMID- 7879475 TI - [The current problems in the epidemiology and prevention of enteric viral hepatitis in Russia]. AB - The presence of great differences in the activity of the epidemic process of hepatitis A (HA) in some regions of Russia is shown and the data necessary for establishing the structure of HA foci in groups of children, as well as the proportion of different forms of the disease registered in such foci (the icteric form in 22.7% of patients, the obliterated form in 11.3% of patients, the nonicteric form in 45.5% of patients and the asymptomatic form in 20.5% of patients), are presented. The study revealed that the shedding of HA virus occurred at an early stage (5-10 before a rise in alanine aminotransferase activity in the blood was registered), its excretion lasted for a short time (till jaundice appeared) and no chronic carriership of HA virus was registered. The hospitalization of HA patients after the appearance of jaundice was proved to be unjustified, while measures aimed at the rupture of the fecal-oral mechanism of the transmission of HA virus were shown to have good prospects. The epidemiological features of hepatitis E (HE) are considered. HE cases constituted 2-3.6% of all patients with acute viral hepatitis in Moscow (all these cases were brought from Central Asia). The outbreaks of this infection in the countries of Central Asia were shown to be due to the transmission of the infective agent by the water route. The data on the first results of the use of high-titer specific immunoglobulin for the prophylaxis of HE among 135 pregnant women (only one of these women contacted HE, while in a similar group of women used for control 4 HE cases were registered) are presented. PMID- 7879476 TI - [Study results and the unresolved problems in the epidemiology and prevention of parenteral viral hepatitis in Russia]. AB - Great differences in the activity of the epidemic process of hepatitis B (HB), the occurrence of HBsAg among the population of different regions of Russia (in the central and northwestern regions among 1.8-2.4% of the population, in Tuva among 9.8% of the population, in Yakutia among 11.6% of the population) and considerable differences in the occurrence of HBeAg among HBsAg carriers in these regions (antibodies to delta virus have been detected in 1.3-5.5% of carriers of this antigen in the European part of Russia and in 21.0% of carriers in Tuva) are shown. The structure of the transmission routes of HB virus, the proportion of the artificial and natural routes of its transmission are analyzed. The data on the frequency of cases of perinatal and intrafamily HB virus infection in regions with different activity of the epidemic process, as well as the data on effectiveness of measures for the prevention of posttransfusion HB and parenteral infection during therapeutic and diagnostic interventions, are given. The results of the use of Engerix B vaccine among 2,500 persons belonging to groups of risk are presented. The proportion of hepatitis C (HC) cases among patients with different kinds of acute and chronic viral hepatitis among the population of different regions and the occurrence of anti-HC antibodies among the population of different regions of Russia (in Moscow and St. Petersburg among 1.1-1.2% of the population, in North Caucasia among 4.5% of the population), as well as in high risk groups (3.1% among medical personnel, 19.4% among drug addicts, 25% among patients of hemodialysis wards, ets), are considered. The structure of transmission routes of HC virus is analyzed, the possible measures for the prophylaxis of HC virus infection are considered. PMID- 7879477 TI - [The mixotrophy of pathogenic bacteria]. AB - This work deals with materials on the utilization of carbon dioxide and hydrogen from gas-air mixture by Yersinia pseudotuberculosis and Listeria monocytogenes in the process of their cultivation in Hirsch's mineral medium. As follows from the data presented in these materials, the above-mentioned bacterial species are heterotrophic when the infectious process is reproduced in the body of warm blooded animals and chemolithoautotrophic under the conditions of their life in environmental objects. Such a wide range of their metabolic plasticity ensures the dual character of their saprophytic and parasitic nature. PMID- 7879478 TI - [The manifestations of an epidemic process in a respiratory streptococcal infection among ships' crews under commercial sailing conditions]. AB - Morbidity in respiratory streptococcal infection in 6 ships of the State Fishery Amalgamation "Dal'ryba" during 8 voyages was analyzed. During voyages morbidity rate is determined by sporadic cases, seasonal rises at the time of the voyage and epidemic outbreaks. Spring and summer months constitute the period of risk for seasonal morbidity rises during voyages and epidemic outbreaks at the time of the formation of the crew. The minimal size of the crew in which the activation of the epidemic process took place was 350 persons. In lesser crews (250-300 persons) seasonal rises in morbidity were observed only in the presence of frequent and intensive change-over of crew members. PMID- 7879479 TI - [A prognostic model of a cholera epidemic]. AB - A new model for the prognostication of cholera epidemic on the territory of a large city is proposed. This model reflects the characteristic feature of contacting infection by sensitive individuals due to the preservation of Vibrio cholerae in their water habitat. The mathematical model of the epidemic quantitatively reflects the processes of the spread of infection by kinetic equations describing the interaction of the streams of infected persons, the causative agents and susceptible persons. The functions and parameters of the model are linked with the distribution of individuals according to the duration of the incubation period and infectious process, as well as the period of asymptomatic carrier state. The computer realization of the model by means of IBM PC/AT made it possible to study the cholera epidemic which took place in Mexico in 1833. The verified model of the cholera epidemic was used for the prognostication of the possible spread of this infection in Guadalajara, taking into account changes in the epidemiological situation and the size of the population, as well as improvements in sanitary and hygienic conditions, in the city. PMID- 7879480 TI - [The morbidity and immunological structure of the population in viral hepatitis A at different phases in the development of multiyear epidemic cycles]. AB - For the first time population immunity to virus hepatitis A has been studied during three different phases of prolonged morbidity cycles of this infection, and the results of this study have been compared with the data on morbidity in different age groups. Pronounced variability of the immunological structure of the population in different age groups, found to be related to the dynamics of hepatitis A morbidity, has been established. Fluctuations in immunity level are most pronounced among children aged 1-6 and 7-14 years, having the least proportion of seropositive persons. A new epidemic cycle is started among these groups of the population, and at the first stage this cycle is manifested by an increase in the intensity of the latently developing epidemic process. This is followed by the activation of registered morbidity among the whole of the population. Seroepidemiological study may be used both for prognostication purposes and in the system of surveillance on this infection. PMID- 7879481 TI - [A prognostic model of hepatitis A morbidity]. AB - The growing interest to the study of the processes of the spread of hepatitis A (HA) in big cities of our country has stimulated the development of a new prognostic model at the Gamaleia Research Institute of Epidemiology and Microbiology. The model specifically takes into account a number of factors linked with the dynamics of the development of the disease in 6 stages and some regularities in the seasonal rises of HA morbidity. Quantitative relations in the mathematical model are determined by a system of nonlinear integral-differential equations with the first order partial derivatives and under the integral type boundary conditions, which increases the strictness of modeling of HA. The use of this new model has made it possible to carry out the prognostic-analytical study of HA morbidity among children in Perm and to evaluate a decrease in HA morbidity due to the hypothetical vaccination of children in spring months. PMID- 7879483 TI - [The morphological changes in the body of guinea pigs in response to the administration of different Coxiella burnetii antigens]. AB - In this work the evaluation of macro- and micro-changes in the tissues of guinea pigs to the injection of inactivated antigens of C. burnetii is presented. The injection of these antigens in a dose of 50 micrograms induced only an insignificant reaction at the site of injection; in the brain of the animals, as well as in all examined internal organs, no visible pathological changes were present. During the first two weeks after the injection of the antigens signs of irritation of the reticuloendothelial system and hyperplasia of lymphoid tissue in T- and B-dependent zones were observed in the regional lymph nodes of the experimental animals. These changes became moderate by day 28. PMID- 7879482 TI - [Combined (associated) vaccination against quarantinable infections]. AB - The presence of several active foci of infection of different etiology is an indication for complex (combined) immunization against these diseases. The scheme of complex (combined) immunization against plague, cholera and yellow fever has been experimentally substantiated and successfully tested on volunteers. PMID- 7879484 TI - [The patterns of the corrective action of a natural immunomodulator on the secondary immunological defect caused by a corpuscular pertussis vaccine]. AB - Purified staphylococcal toxoid (PST) was shown to be capable of preventing the development of secondary antigen-nonspecific immune deficiency in mice, immunized with whole-cell pertussis vaccine. The immunocorrective action of PST was manifested after its injection before (on day -1), simultaneously with and after (on day +1) the injection of whole-cell pertussis vaccine. Correction was either complete or partial, depending on the scheme of the experiment and the dose of PST. PMID- 7879485 TI - [The early laboratory diagnosis of the pulmonary form of glanders and melioidosis by using rapid methods of immunochemical analysis]. AB - The problems of the sanitary guarding of frontiers comprise such aspects as the early recognition of infectious diseases, even those which are considered exotic in the Russian Federation. These diseases include glanders and melioidosis, infections which are endemic for some frontier regions. The study performed on experimental models of the pulmonary form of glanders and melioidosis with the acute course of the diseases demonstrates that the use of such laboratory diagnostic methods as immunosorbent variants of the enzyme-linked, chemiluminescent and immunofluorescent immunoassays permits making reliable diagnosis as early as 3-12 hours after aspiration infection. PMID- 7879487 TI - [The immunological activity of the bacterial strain Escherichia coli M17 used in preparing a commercial preparation of colibacterin]. AB - The toxicity, immunogenic properties and protective activity of the live culture of E. coli M17 and antigenic preparations obtained from cell suspensions of this strain have been studied under experimental conditions. As revealed in experiments on mice, E. coli M17 live culture has low virulence, moderate toxicity and provides the protection of immunized mice from challenge with homologous and highly virulent E. coli strains. E. coli M17 live culture, when introduced orally or intravenously into rabbits, ensures the synthesis of 02 and H6 antibodies. Blood sera taken from immunized rabbits yield better results than initial sera in experiments on the passive protection of mice. The results of our experiments show the expediency of the clinical trials of Colibacterin as a perspective Escherichia live oral vaccine. PMID- 7879486 TI - [The development of nutrient media for the cultivation of recombinant Escherichia coli strains]. AB - The study of the qualitative and quantitative composition of peptides and free amino acids in commercial casein hydrolysates, produced in Russia, has provided grounds for the choice of the nutrient base in the medium for the cultivation of E. coli recombinant strains. In the newly developed medium specific endoglucanase activity is 1.5- to 1.7-fold greater than in Luria-Bertani broth ("Difco" Laboratories, USA). PMID- 7879488 TI - [The clinico-immunological characteristics and treatment of an intestinal infection of Klebsiella etiology]. AB - The examination of 265 patients with the diagnosis of acute enteric infection (AEI) of Klebsiella revealed that the disease took a mild course in 40%, a moderate course in 45.3% and a severe course in 14.7% of the patients. The clinical syndromes of acute gastritis, gastroenteritis, enteritis were observed; in cases of the severe course of AEI the hemolytic [correction of hemocolitic] syndrome was present. Immune shifts were characterized by T lymphopenia, a decrease in the number of T helpers/inductors (CD 4), the immunoregulatory indices (CD 4/CD 8), an increase in the level of circulating immune complexes. These levels reached their maximum in case of the severe course of Klebsiella infection and were retained till the patient was discharged from the hospital and, if any concomitant pathology was present, even for 1-3 months after discharge. PMID- 7879489 TI - [The possible mechanism in the formation of epidemic variants of the causative agents of sapronoses in the soil or water]. PMID- 7879490 TI - [The B protein of Streptococcus group B: the current concepts of its structure, the mechanism of its interaction with membranes and its biological properties]. PMID- 7879491 TI - [The role of the activity of pathogenic enterobacteria in inactivating the antibacterial constituent of interferon during phagocytosis]. PMID- 7879492 TI - [The importance of serological methods in the diagnosis of Q fever in western Ukraine]. PMID- 7879493 TI - [A fluorescent probe method in allergological diagnosis]. PMID- 7879494 TI - [The isolation and purification of a staphylococcal exotoxin in toxic shock and the production of antisera]. PMID- 7879495 TI - [The intestinal microecology of newborn and young infants with perinatal pathology]. PMID- 7879496 TI - [The mechanisms of action of probiotics on lymphocyte function in acute shigellosis]. PMID- 7879497 TI - [The efficacy of using bifidokefir for the treatment of acute intestinal infections and for the correction of dysbacterosis in children]. PMID- 7879499 TI - [The mycological spectrum in a kidney transplantation department]. PMID- 7879498 TI - [The observation of the circulation of hospital microflora in a burn hospital by using electrophoretic protein analysis]. PMID- 7879500 TI - [The stimulating effect of Aerococcus viridans on phagocytosis and antibody formation]. PMID- 7879501 TI - [Local immunity in microecological disorders in children with gastroduodenal pathology]. PMID- 7879503 TI - [The development of rapid methods for monitoring the microbial ecology of people in contact with xenobiotics]. PMID- 7879502 TI - [Staphylococci in the skin microbiocenosis of the hands in workers of assembly plants and metal-working shops]. PMID- 7879504 TI - [The results of an intensified examination of epidemiologically dangerous blood donors]. PMID- 7879506 TI - [The biological properties of mobile enterococci]. PMID- 7879505 TI - [The functional metabolic activity of the leukocytes in scarlatina, measles and parotitis in adults]. PMID- 7879507 TI - [Complications in experimental influenza impeding the development of complete resistance to reinfection]. PMID- 7879508 TI - [The growth kinetics of Pseudomonas putida and its determining factors]. PMID- 7879509 TI - [New species of pathogenic vibrios isolated from people as well as from the waters of the Black and Baltic seas]. PMID- 7879510 TI - [The fatty acid composition of Yersinia pestis grown on different nutrient media at 28 and 37 degrees C]. PMID- 7879511 TI - [The effect of the components of Bordetella pertussis lipopolysaccharides on Rauscher virus-induced leukosis in mice]. PMID- 7879512 TI - [Solar activity and the production of aggression factors by opportunistic microorganisms]. PMID- 7879513 TI - [The etiological structure of food poisonings caused by marine halophilic vibrios]. PMID- 7879514 TI - [The isolation and acylase (N-acylamino acid amidohydrolase) characteristics of Providencia alcalifaciens]. PMID- 7879515 TI - [Microbiological nutrient media based on the wastes from fur farming]. PMID- 7879518 TI - [The biochemiluminescence of Escherichia coli and Shigella sonnei strains with a transmitted luminescence plasmid]. PMID- 7879517 TI - [The interrelation of the composition of the nutrient media with the growth and biological properties of Bordetella pertussis]. PMID- 7879516 TI - [The characteristics of the Staphylococcus aureus populations during the long term course of the inflammatory process in a model kidney infection in mice]. PMID- 7879519 TI - [A comparison of streptococci groups A, C and G by the spectra of their surface proteins]. PMID- 7879520 TI - [The age-related biological pattern in freeing the body of patients from causative agents]. PMID- 7879521 TI - [The biological activity of museum and freshly isolated Pseudomonas aeruginosa cultures and the possible phase transformations in populations of the causative agent]. PMID- 7879522 TI - [The sensitivity to the bactericidal action of normal blood serum of Escherichia coli strains containing plasmids for multiple drug resistance]. PMID- 7879523 TI - [The genomic characteristics of thermostable mutants of Lactobacillus acidophilus]. PMID- 7879524 TI - [Low-molecular plasmids--a prospective test for the intraspecific differentiation of Yersinia pestis]. PMID- 7879525 TI - [The structure of populations of Pseudomonas aeruginosa in association with staphylococci and Escherichia]. PMID- 7879526 TI - [The detection of Chlamydia trachomatis by the polymerase chain reaction]. PMID- 7879527 TI - [The displacement of virulent Salmonella typhimurium bacteria by a microcin producing Escherichia coli strain in their combination in the hemocele of arthropods]. PMID- 7879528 TI - [Class-M and -G antipolysaccharide antibodies in human immunoglobulin preparations]. PMID- 7879530 TI - [The echinococcosis problem in the Russian Federation]. PMID- 7879529 TI - [The humoral immune response to the antigens of the transient autologous intestinal flora in acute respiratory viral infections in children]. PMID- 7879531 TI - [The epidemiological determinants of the irregular territorial prevalence of enteric viral hepatitis]. PMID- 7879532 TI - [Validation of the choice of the optimal immunopharmacological schemes for performing mass antigen-nonspecific immunoprophylactic measures]. PMID- 7879533 TI - [The Vibrio flora of the bodies of water in the recreational areas along the Black Sea shore and its role in human pathology]. PMID- 7879534 TI - [The isolation of the surface antigens of Candida tropicalis and their immunochemical characteristics]. PMID- 7879535 TI - [Bacteria of the genus Yersinia in the drinking water sources of Vladivostok]. PMID- 7879536 TI - [The organizational epidemiological problems of performing mass antigen nonspecific immunoprophylactic measures]. PMID- 7879537 TI - [The seasonality of Sonne dysentery among preschoolers]. PMID- 7879538 TI - [An evaluation of the efficacy of measures to limit the activity of the water factor in the transmission of shigellosis in the city of Blagoveshchensk]. PMID- 7879539 TI - [The seroepidemiological screening of the blood serum in occupational risk groups for Campylobacter infection]. PMID- 7879540 TI - [An outbreak of influenza-adenoviral infection in children]. PMID- 7879541 TI - [An analysis of the etiological structure of acute viral hepatitis in children over a 10-year interval based on the serological screening data at a hospital]. PMID- 7879543 TI - [The interrelationships of the territories with an infection risk for the population within the limits of the nosogeographical ranges of tick-borne rickettsiosis and tick-borne encephalitis]. PMID- 7879542 TI - [Leptospirosis in Bangladesh]. PMID- 7879544 TI - [The functional activity of wound mononuclear phagocytosing cells in revaccination with a Clostridium perfringens anatoxin]. PMID- 7879546 TI - [The immunological activity of a meningococcal serogroup-B polysaccharide-protein vaccine with a prolonged storage time in single administration]. PMID- 7879545 TI - [The effect of multiple plague vaccination on immune system indices]. PMID- 7879548 TI - [The isolation of mutant Salmonella cholerae-suis with the CYA and CRP phenotypes and a study of their biological properties]. PMID- 7879547 TI - [An analysis of the plasmid profile of Shigella flexneri strains used for obtaining vaccinal preparations]. PMID- 7879549 TI - [The etiological structure of shigellosis in monkeys of the Adler Nursery]. PMID- 7879550 TI - [The immunogenic properties of liposomal preparations formed from a base of phospholipid antigenic complexes]. PMID- 7879551 TI - [The dynamics of immunoglobulin E in volunteers immunized with a meningococcal group-B polysaccharide-protein vaccine]. PMID- 7879552 TI - [The role of Legionella pneumophila membrane proteins in forming cell-mediated immunity]. PMID- 7879553 TI - [An evaluation of the possibility of obtaining an inactivated vaccine against Lassa fever]. PMID- 7879554 TI - [The immunogenic and antigenic properties of the individual fractions of tetanus anatoxin]. PMID- 7879555 TI - [Changes in the direction of the immunomodulating activity of a purified staphylococcal anatoxin when administered to virus-infected mice]. PMID- 7879556 TI - [ADTP vaccine induces temporary immunosuppression correctable by using the immunomodulator purified staphylococcal anatoxin]. PMID- 7879557 TI - [The determination of antibodies to Bordetella pertussis exotoxin in donor sera and in the raw material for obtaining normal human immunoglobulin]. PMID- 7879558 TI - [Helicobacter pylori in patients with gastroduodenal pathology at a young age]. PMID- 7879559 TI - [Immunodiagnosis and the characteristics of the immune response in chronic tonsillitis of a staphylococcal etiology]. PMID- 7879560 TI - [Experience in using immunoenzyme analysis for the diagnosis of pertussis]. PMID- 7879561 TI - [The functional status of the neutrophil-monocyte system in generalized forms of meningococcal infection in children]. PMID- 7879562 TI - [The characteristics of the immune response in children having different HLA phenotypes after the first revaccination with ADTP]. PMID- 7879563 TI - [The dynamics of the antibody titers to Re-glycolipid in peritonitis patients during the performance of antiendotoxin immunotherapy]. PMID- 7879565 TI - [Changes in the ultrastructure and enzyme activity of the peritoneal macrophages in mice exposed to the influenza virus]. PMID- 7879566 TI - [The role of tumor necrosis factor-alpha in the pathogenesis of an experimental infection induced by Yersinia pestis]. PMID- 7879564 TI - [Phages of the IV serovar of Yersinia pestis]. PMID- 7879567 TI - [The characterization of the protective properties of antiplague preparations by using the index of macrophage subpopulation redistribution]. PMID- 7879568 TI - [The demonstration of bacterial antigens in milk]. PMID- 7879569 TI - [The preparation of latex diagnostic agents based on the surface antigens of Candida tropicalis]. PMID- 7879570 TI - [A new method for determining the complement-mediated bacteriolytic action of serum on Escherichia coli cells]. PMID- 7879571 TI - [Stimulation of maturing and terminal differentiation by concanavalin A in rabbit permanent chondrocyte cultures]. AB - The effect of concanavalin A (Con A) on maturing and terminal differentiation in permanent chondrocyte cultures were examined. Chondrocytes isolated from permanent cartilage were seeded at low density and grown in MEM medium containing 10% fetal bovine serum, 50 micrograms/ml of ascorbic acid and antibiotics, at 37 degrees C under 50% CO2 in air. At 0.3% of low serum concentration, addition of Con A to the culture medium increased by 3- to 4-fold the incorporation of [35S] sulfate into large chondroitin sulfate proteoglycan that characteristically found in cartilage. Chemical analysis showed a 4-fold increase in the accumulation of macromolecular containing hexuronic acid in Con A-maintained cultures. The effect of Con A on [35S]sulfate incorporation into proteoglycan was greater than that of various growth factor or hormones. Brief exposure of the permanent chondrocytes to Con A (5 micrograms/ml) for 24 hours and subsequent incubation in its absence for 5-10 days resulted in 10- to 100-fold increase in alkaline phosphatase and binding of 1.25 (OH)2 vitamin D3 to cells. Treatment with Con A also resulted in 10- to 20-fold increase in calcium content and 45Ca incorporation into insoluble material. Methyl-D-mannopyranoside reversed the effect of Con A on [35S]sulfate incorporation into proteoglycan and alkaline phosphatase activity. Since other lectins, such as wheat germ agglutinin, lentil lectin, phytohemagglutinin, Ulex europeasu agglutinin and garden pea lectin had been tested to have little effect on [35S]sulfate incorporation into proteoglycans and induction of alkaline phosphatase activity, the Con A action on chondrocytes seems specific. These results indicate that Con A is a potent modulator of differentiation of chondrocytes, which induces the onset on a maturing and a terminal differentiation in chondrocytes, leading to extensive calcification of the extracellular matrix. PMID- 7879572 TI - [Functional roles of LFA-1 involved in signal transduction for thymocyte activation]. AB - The biological significance of the signals triggered by the interaction of cell surface expressed LFA-1 and ICAM-1 has been investigated in Con A and immobilized anti-CD3 mAb stimulated cultures. When added at the beginning of activation in the presence of Con A, soluble anti-LFA-1 and anti-ICAM-1 mAbs could strongly inhibit cell proliferation. Such inhibitory effect was also exhibited in the proliferative response of thymocytes to immobilized anti-CD 3 mAb activation. However, the soluble anti-LFA-1 mAb was unable to inhibit the proliferation of primed thymocytes preactivated with Con A for 24 h or of IL-1 + IL-2 activated fresh thymocytes. Anti-LFA-1 mAb could profoundly inhibit Con A-induced thymocytes to produce IL-2 and IL-6 and to reduce IL-2 receptor expression. By contrast, anti-LFA-immobilized on plastic plates together with immobilized anti CD 3 mAbs or CD 3 cross-linking with LFA-1 by secondary antibodies resulted in an enhanced activation signals for thymocytes to proliferate compared with that activated by anti-CD 3 alone. Thus, mAb to LFA-1 is a functional molecule for thymocyte activation, mediating signals contributed to very early phases of signal transduction through TCR/CD 3 pathway, and that LFA-1 might provide a costimulatory signal for expression of IL-2 R and IL-2 production. PMID- 7879573 TI - [The meiosis arrest of mouse oocytes induced by adenine]. AB - The effect of purine on the meiosis of mouse oocytes was studied. When adenine and benzyladenine, a similar substance of adenine, was microinjected into the germinal vesicle of oocytes, the meiotic maturation of oocytes could be obviously arrested depending on the dosage of injection. The stimulator of adenylate cyclase, NaF, could enhance the arrest effect of adenine. It indicated that cAMP played a important role in mouse oocytes meiotic resumption. Hypoxanthine and adenine had different effects in different medium. Hypoxanthine could obviously arrest the maturation of mouse cumulus oocyte complex (COC) and cumulus denuded oocytes (DO) in DMEM or EMEM. But only in DMEM adenine could obviously arrest the maturation of COC, and had co-effect with hypoxanthine in DMEM. They could almost arrest the maturation of COC and DO. Adenine in EMEM had little arrest effect on maturation of COC and DO. The different effects may result from the different adenine absorption by oocyte in DMEM and EMEM. Adding glutamine into EMEM could enhance the arrest effect of adenine to COC and DO. PMID- 7879574 TI - [The effect of wheat germ agglutinin on anion transport in the erythrocyte membranes]. AB - The wheat germ agglutinin (WGA) has been recognized as the lectin that can agglutinate human erythrocytes. It is reported recently that the binding of WGA to the glycophorin blocks the morphological conversions of discocyte<- >echinocyte. Glycophorin is thought to be associated with Band 3, the anion transport protein, via the cytoskeleton proteins Band 4.1, spectrin and ankyrin. The effect of WGA on the anion transport across the erythrocyte membranes was measured by NO2- transport and NH4 Cl isotonic swelling, two different methods developed by our laboratory in recent years. The results showed that the rate of anion transport was decreased, depending on WGA concentration. This effect became saturated when WGA concentration reached 2-3 micrograms/ml. We have also observed that in certain conditions when the morphological conversion of discocyte- >elliptocyte was induced by high concentration of WGA, the rate of anion transport could be reversely increased. Furthermore, the effect of WGA on erythrocyte osmotic fragility was studied. The results indicated that the osmotic fragility was reduced after adding WGA to the erythrocyte suspension, which means the erythrocyte cytoskeleton is more stable under this condition. All effects that WGA exerted above were instantly abolished by adding N-acetylglucosamine which has specific binding sites on WGA. In conclusion, the binding of WGA to the sialic acid groups of glycophorin can lead to the conformational changes in saccharides and such changes will be transferred via glycophorin, cytoskeleton to Band 3, which causes the final change of anion transport. The effect is indirect, so the change is small (approximately 10%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879575 TI - [Studies on the centrosome antiserum from a scleroderma patient]. AB - Using ascites cells as screening system and by means of indirect immunofluorescence microscopy, several antisera against centrosome from scleroderma patients were discovered. Since centrosome is chemically complex cellular structure and the autoimmune antiserum is polyclonal, further investigation was made using one of the antisera against centrosome. L929 cultured cells were also employed for the antigen localisation. It was found that the antiserum decorated microtubules, mitotic spindle, centrosome as well as some nuclear structure. Immunoblots of the cell lysate with the antiserum revealed that in addition to the main bands of tubulin there were several less distinct bands. This result confirmed the indirect immunofluorescence observation. PMID- 7879576 TI - [Cloning and screening on tumor-related genes inactivated in rat hepatoma cells]. AB - The paper describes an experiment screening tumor-related genes which specifically expressed in rat normal liver cells but inactivated in hepatoma cells with subtractive hybridization technique. During the test, subtracting normal liver cDNA with hepatoma mRNA produces probe-A whereas subtracting hepatoma cDNA by normal liver mRNA gives probe-B. The paper shows six cDNA fragments (TR 1-6) which hybridize probe-A preferentially obtained through dot blot screening of 2500 colonies with the two probes. Among TR 1-6, special expressions of TR 2 and TR 4 in normal liver cells are further analyzed. PMID- 7879577 TI - [The study of metaphasic chromosome pellicle]. AB - Among 12 antichromosome antisera from scleroderma patients, four were found to be the antisera against the pellicle of metaphase chromosomes. Western blotting with these sera were achieved on the protein bands resolved by SDS-PAGE of the whole cell lysate and nuclear lysate of the ascites cells. The result showed 11 bands of the nuclear lysate reacted with antisera. Moreover, additional 8 were obtained in the whole cell lysate. PMID- 7879578 TI - [Fluorescent in situ hybridization of enriched SFA-DNA on pachytene chromosomes in mouse]. AB - In the present study, the primary constrictions of mouse pachytene chromosomes stained with Hoechst 33258, and those stained by indirect immunofluorescence method with CREST antiserum were compared with those hybridized by the probe DNA isolated from the enriched mouse spindle fiber attachments. It was found that the DNA probe hybridized not only with the centromeric regions on synaptonema complexes but also with the DNA of pericentromeric heterochromatin of all autosomes. Moreover, the DNA probe hybridized also with the centromeric regions of both X and Y chromosomes. It was concluded that the DNA isolated from the enriched mouse spindle fiber attachments contains a complete set of the centromeric DNAs of all autosomes, X and Y chromosomes. PMID- 7879579 TI - Status of AANA's four priorities in draft Senate mainstream coalition healthcare reform bill. PMID- 7879580 TI - JCAHO accreditation. PMID- 7879581 TI - An international study of educational programs for nurses providing anesthesia care. PMID- 7879582 TI - Statute of limitations. PMID- 7879583 TI - Ventilation monitoring during monitored anesthesia care: a review. AB - The use of capnography during general anesthesia has become not only state of the art but also a recommended standard of care. In intubated patients, measurements of partial pressure of carbon dioxide in exhaled pulmonary gases approximate partial pressure of carbon dioxide in arterial blood under stable conditions. End tidal carbon dioxide measurement has allowed anesthetists to continuously follow carbon dioxide concentration in exhaled gases; indirectly, it has enabled them to continuously monitor carbon dioxide concentration in arterial blood. This information has proven indispensable in the care of patients receiving general anesthesia, with its accompanying respiratory depressant effects. Recently, attention has focused on the utilization of capnography in sedated, nonintubated patients to follow carbon dioxide concentrations and access respiratory system function. This review of the current body of literature outlines development in capnography monitoring for sedated, nonintubated patients. Emphasis is placed on current techniques of measurement, the degree of correlation, and ramifications for clinical practice. PMID- 7879584 TI - The Tec 6 vaporizer: why desflurane needs to be heated. AB - The Ohmeda Tec 6 was designed as an agent-specific vaporizer for desflurane. Its exterior framework offers some unique features. Aside from its unique filling port, broad calibration range, and additional light-emitting diodes (LEDs), its large size literally sets it apart from all other models. As distinctive as the exterior appears, its interior design is even more unconventional; that is, it is not a variable-bypass, flow-over system. There are no mixing chambers, baffles, or temperature-sensing bellows; a differential pressure transducer system takes their place. Many modifications were made primarily to accommodate the remarkably high vapor pressure of desflurane. This is especially true in regard to the sump heating unit. Although there are many options to accommodate a high vapor pressure, a heating unit serves the purpose best. A brief review of vaporization and fundamental thermodynamics will demonstrate why this is so. PMID- 7879585 TI - An anesthetic for the adult patient with congenital tracheoesophageal fistula: a case report. AB - A 20-year-old male with a history of recurrent pneumonia was diagnosed as having an N-type tracheoesophageal fistula. A general anesthetic was planned to facilitate the repair of the tracheoesophageal fistula using a left anterior cervical approach. Intraoperatively, the surgeons were unable to identify the defect after surgical exposure. To facilitate location of the tracheoesophageal fistula, a flexible pediatric fiberoptic bronchoscope was passed through an elbow adapter connected to the endotracheal tube. The scope was then visually passed via the trachea through the defect into the esophagus. The surgeons were able to palpate the fistula with the bronchoscope passed through the defect. Ease of identification allowed the tracheoesophageal fistula to be quickly repaired. At the completion of the surgery, the patient was extubated, and recovery was uneventful. The patient was discharged 48 hours postoperatively. PMID- 7879586 TI - AANA journal course: update for nurse anesthetists--"is it okay to breast feed my baby after anesthesia?" A scientific basis for an informed response. AB - Many breast-feeding women are exposed to anesthetic drugs. The question of breast feeding following an anesthetic is a highly relevant issue in part because it is desirable to allow breast feeding to resume quickly while minimizing the potential for drug-related infant morbidity. The physiology of breast milk production and the factors influencing the transfer of drugs into breast milk is reviewed. Generally there is incomplete or sparse information on the potential effects upon the suckling infant. Despite this, certain reasonable conclusions and recommendations can be developed. Among these include a substantive risk with high-dose and long-standing therapies, particular vulnerability in the premature neonate or when a mother is receiving multidose therapy, and consideration of temporarily interrupting the feeding schedule where sufficient doubt exists. Overall, the importance of breast feeding must be carefully considered in light of the potential for side effects in each maternal/child scenario. PMID- 7879587 TI - Attitudes of nurse anesthetists regarding choice of residence and job satisfaction in Nebraska. AB - Nebraska CRNAs were surveyed to identify their attitudes regarding choice of residence and to rate their overall job satisfaction. In addition, the study determined differences in these attitudes, based on employment and whether they resided in a metropolitan or rural setting. Places of residence and employment in Nebraska were grouped according to population. Metropolitan areas consisted of Omaha/Douglas County and Lincoln whose populations were greater than 200,000. Moderately sized communities, where rural referral centers are located, were grouped together, and by default other communities were considered to be smaller rural communities. With a 76% response rate (n = 168), the survey demonstrated no significant difference among the four regional CRNA groups with regard to overall job satisfaction. There were however, areas of significant difference among the CRNA groups with regard to the components of job satisfaction; this was most apparent between the rural referral center and the Lincoln CRNA groups. The rural referral center CRNA group rated the following significantly higher from the Lincoln CRNA group: 1. Autonomy. 2. Experiencing positive CRNA/surgeon relationships. 3. The opportunity to improve professional skills. 4. The opportunity to meet professional goals. 5. The ability to practice anesthesia as trained. Conversely, the Lincoln CRNA group rated having "sufficient time away from work" higher than all other CRNA groups. All CRNA groups rated "quality of life" as the leading environmental reason for choosing their place of residence. In addition, the CRNA groups rated these reasons for choosing their communities: 1. Affordable housing. 2. Quality public schools. 3. A clean environment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879588 TI - A biomechanical perspective on spinal mechanisms of coordinated muscular action: an architecture principle. AB - A principle of organization of spinal circuitry which emerges from the studies reviewed here is that the structure of the distributed network of pathways in the spinal cord contains a detailed representation of the corresponding three dimensional architecture of the musculoskeletal system. The pertinent architectural features for a given muscle include (1) the number and identity of spanned joints, and (2) the line of action at a joint with respect to the torque directions of other muscles and to the gravity vector. In accordance with established ideas, muscles with common primary actions (synergists) at the ankle are linked by excitatory, length-dependent pathways. Those muscles which have opposite actions are linked by reciprocal inhibition, although muscles which are not principally involved in postural control are not connected in this way. Among antigravity and stabilizing muscles, force-dependent, inhibitory pathways link (1) muscles crossing different joints, and (2) members of different synergistic groups which exert torques in different directions. Therefore, each muscle has a unique set of actions in terms of joints spanned and line of action, and each muscle receives a unique combination of reflex inputs. The cross-joint coordination resulting from actions of force-dependent pathways becomes stronger at higher forces with a consequent reduction in degrees of freedom of the musculoskeletal system. Length-dependent pathways link muscles which share some, but not all, mechanical actions at a joint and may have different patterns of activation during locomotion. Length-dependent pathways appear to coordinate muscle responses to postural disturbances and enhance joint stiffness. PMID- 7879589 TI - Study of pterygospinosus muscle in human fetuses. AB - The arrangement of the pterygospinosus muscle was analyzed in 5 human fetuses. The pterygospinosus muscle extends from the posterior border of the lateral lamina of the pterygoid process to Meckel's cartilage. Such an arrangement would permit its action on the joint formed by Meckel's cartilage and the incus of the middle ear. The pterygospinosus muscle is a remnant of the masticatory muscle group. The relationships of the pterygospinosus muscle with the mandibular nerve and its branches and the maxillary artery and its branches were analyzed. PMID- 7879590 TI - Development of the anal fin appendicular support in the western mosquitofish, Gambusia affinis affinis (Baird and Girard, 1854): a reinvestigation and reinterpretation. AB - Development of the sexually dimorphic anal fin appendicular support of an internal fertilizing bony fish Gambusia affinis affinis was investigated by staining whole-mounted embryos, immature, and adult female and male G. a. affinis with alizarin red S and alcian blue. The tissue was examined histologically to assess development of the amphicelous centrum and to verify specificity of the stains. Our data confirm earlier claims about the development of the male and female characteristics in this species, and we provide for the first time direct embryonic evidence suggesting that development of the sexually dimorphic anal fin appendicular support is biphasic: (1) anteriorization of the most anterior caudal segments, and (2) growth and elongation of hemal arches of vertebrae 14-16. The first process involves a sequential homeotic transformation of hemal arches of vertebrae 11-13 through resorption of mineralized connective tissue, thus forming parapophyses that bear pleural ribs. This process begins in undifferentiated embryos and proceeds similarly in postnatal males and females. During the same period, the second process, likely induced by male gonadal hormones, causes the addition of mineralized connective tissue at the hemal arches of vertebrae 14-16. This second process, which occurs only in males, elongates the hemal arches of vertebrae 14-16 anteriorly. This elongation apparently translocates the anal fin appendicular support (including parts of the hemal spine of the hemal arch of vertebra 13) to the level of vertebra 11. It appears that the developmental programs of both female and male G. a. affinis create an area of 6 vertebrae which are markedly different from any vertebrae anterior to 11 and posterior to 16. We propose to term the area including these vertebrae and the associated anal fin, the genital area. We also propose that the first process, homeotic transformation of caudal into precaudal segments, is regulated by differential expression of control genes, such as homeobox genes, whereas the second process is regulated by gene expression under the control of male gonadal hormones. Conflicting data in the literature can be resolved with this model. Appropriate tests of the model are proposed. PMID- 7879591 TI - Scanning electron microscopy of collagen fiber orientation in the bone lamellar system in non-decalcified human samples. AB - Previous studies on collagen fiber orientation have led to different interpretations and theories about the fiber arrangement in the lamellar compact bone. The purpose of this investigation was to provide new and more in-depth data on fiber arrangement in the lamellar bone system in order to explain the orientation of the fiber bundles. This was carried out by applying a simple method of preparation which permitted observation of non-decalcified samples. A previously isolated Haversian system was subjected to slow bending up to reaching the fracture point. Hence, the fracture surface was observed by SEM. The same samples were also observed by polarized light microscopy. A significant alternation of fiber orientation in the adjacent lamellae was observed. Different domains of differently oriented fibers were present within the same lamella; conjugating fibers connecting adjacent lamellae were also shown. This method avoided most of the artifacts due to chemical treatment of bone samples. The results can be easily interpreted by means of the same criteria applied in mechanics for the studying of composite materials. PMID- 7879592 TI - Observations on the vomeronasal organ of the colugo Cynocephalus (Mammalia, Dermoptera). AB - This paper presents the first description of a functional vomeronasal organ in the colugo or 'flying lemur' Cynocephalus, the sole living representative of the order Dermoptera (Mammalia). The vomeronasal organ complex comprises patent nasopalatine and vomeronasal ducts, a 10-mm-long epithelial tube consisting of an 8- to 10-cell thick, 65-microns-tall neurosensory epithelium, the vomeronasal nerve, and the accessory olfactory bulb. The vomeronasal glands are sparse. Among mammals, the vomeronasal organ of the colugo is one of the relatively longest, at nearly 48% of nasal cavity length. It is exceeded among archontans (colugos, bats, primates, and tree shrews) only by that of the strepsirhine primate Microcebus murinus. PMID- 7879593 TI - Paneth cells of African giant rats (Cricetomys gambianus). AB - The ultrastructure of Paneth cells of African giant rats (Cricetomys gambianus), which were captured on the savanna in western Africa, was studied. The Paneth cells of Cricetomys were clustered at the bottom of crypts of the small intestine, but not of the colon. In the normal state, Paneth cells had a few secretory granules showing high electron density. Small clear vesicles which are a characteristic in laboratory albino rats were not conspicuous. Vacuolated Paneth cells and secreted materials from the Paneth cells were frequently found. This suggests that the secretion of Paneth cells of Cricetomys is active in the natural state. No phagocytotic figures were observed. After atropine sulfate treatment, secretory granules increased in size and number, whereas the electron density decreased, similar to that of goblet cell granules. However, the granules were not stained by alcian blue or by PAS. Inhibition of secretory stimuli by atropine can alter the intracellular processing of secretory substances in Paneth cells. PMID- 7879594 TI - Changes in the distribution and intensity of alkaline phosphatase activity in rat lymph node and spleen cells after antigen stimulation. AB - We investigated the reaction of the popliteal lymph nodes (PLN) to the injection of two antigens, keyhole limpet hemocyanin (KLH) and lipopolysaccharide (LPS), into the footpads of rats, as well as the changes occurring in the PLN after allogeneic cell stimulation. Changes in alkaline phosphatase (ALP) activity of the lymph nodes were examined enzyme histochemically. Paralleling with PLN weight gain, increased ALP activity was observed in the medullary regions of the lymph nodes of stimulated rats. ALP reactivity in the stimulated lymph nodes was observed to be weak in the germinal centers and strong in the medullary regions. The spleens of rats subjected to systemic graft-vs.-host (GVH) reaction were examined in a similar fashion. The ALP-positive areas of the GVH spleens increased in size as compared with normal spleens. These positive areas of lymph node and spleen appear to correspond mainly to areas containing OX12-positive cells. These results suggest that enzyme-histochemical analysis of ALP activity together with immunohistochemical analysis of lymphocyte phenotypes may be a useful method for examining lymph node and spleen reactions to soluble and cellular antigens in rats. PMID- 7879595 TI - High division of the axillary artery. A rare case of superficial ulnar artery. AB - A case is presented here in which the axillary artery divided into two branches, the lateral branch being situated more deeply with respect to the medial branch. The superficial branch gave rise to only thin muscular branches in the arm and coursed along the ulnar artery in the forearm but did not provide the branches which should arise from this artery. On the other hand, the deeply coursing artery provided the branches of the brachial artery in the arm and from the cubital fossa downwards it provided the branches which normally arise from the ulnar artery. PMID- 7879596 TI - Amygdala pathology in Parkinson's disease. AB - The amygdala undergoes severe pathological changes during the course of Parkinson's disease (PD). Lewy bodies and Lewy neurites are distributed in a specific manner throughout the nuclear complex. The lesional pattern displays only minor interindividual variation. The most prominent changes occur in the accessory cortical and central nuclei. The cortical, accessory basal and granular nuclei show less severe alterations, while the basal and lateral nuclei, as well as the intercalated cell masses, generally remain uninvolved. The amygdala receives a broad range of afferents, allowing integration of exteroceptive information with interoceptive data. It generates major projections to the isocortex (the prefrontal cortex in particular), limbic system (hippocampus and entorhinal region) and centers regulating endocrine and autonomic functions. The specific lesional pattern seen in PD destroys part of the nuclear gray matter and its connections and, thus, may likely contribute to the development of behavioral changes and autonomic dysfunctions. PMID- 7879597 TI - Neuronal vacuole formation in the rat posterior cingulate/retrosplenial cortex after treatment with the N-methyl-D-aspartate (NMDA) antagonist MK-801 (dizocilpine maleate). AB - Cytoplasmic vacuoles appear in neurons of the posterior cingulate/retrosplenial cortex (PC/RS) of rats after treatment with N-methyl-D-aspartate (NMDA) receptor antagonists. Prominent dilatation of mitochondria and endoplasmic reticulum has been described within 2 h; however, the ultrastructural features of vacuole formation are unknown. To investigate this, the present study examined the PC/RS cortex of male rats (age 60-70 days) at 15, 30, 45, 60, 90, and 120 min after subcutaneous treatment with 1 mg/kg of the noncompetitive NMDA antagonist MK-801 (dizocilpine maleate, 5-methyl-10, 11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10 imine). Subtle mitochondrial dilatation was identified in a few neurons as early as 15 min postdose (MPD). By 30 MPD, dilatation was more pronounced in mitochondria and also involved the endoplasmic reticulum and perinuclear space. Ribosomal disaggregation and degranulation were also evident by 30 MPD. At all subsequent time points, dilatation of mitochondria and endoplasmic reticulum progressed in severity. Although the relative involvement of mitochondria and endoplasmic reticulum varied, glia were not involved. These ultrastructural data suggest that after treatment with MK-801, mitochondrial dilatation precedes involvement of endoplasmic reticulum in vacuolization of susceptible PC/RS cortical neurons. The early mitochondrial effects identified in this study suggest an initial metabolic insult that rapidly progresses to affect endoplasmic reticulum and ribosomes. This strengthens the relationship between the ability of certain NMDA antagonists to induce energy perturbations and neuronal vacuoles in the same region of the rat cerebral cortex. PMID- 7879598 TI - bcl-2 protein expression in tumors of the central nervous system. AB - bcl-2 protein (BCL-2) expression was immunohistochemically studied in 140 varied central nervous system tumors. The protein was most frequently expressed in neurinomas and ependymomas, and in normal ependymal cells and Schwann cells. Most pituitary adenomas could be classified into one of two subgroups, diffusely positive or diffusely negative tumors, while BCL-2 localized heterogeneously in normal pituitary glands. Although the protein was not detected in normal astrocytes, it was positive in reactive hypertrophic astrocytes observed in various pathological conditions. Similarly, astrocytic tumor cells often expressed BCL-2. Since low-grade astrocytomas more often exhibited the protein than malignant gliomas, the degree of BCL-2 expression appeared to be related to the degree of malignancy of the gliomas. On the other hand, 7 out of 17 recurrent gliomas and medulloblastomas showed an increase in the frequency of protein expression compared with specimens from initial treatments. One recurrent astrocytic tumor which demonstrated anaplastic change showed a decrease in the frequency of BCL-2-positive cells. It is concluded that the frequency of BCL-2 expression in CNS tumors is increased when the non-neoplastic counterparts of the tumors exhibit the protein. Although it has been reported that overexpression of BCL-2 protects cells from damage by radiation and/or chemotherapy, we could not find any significant relationship between the degree of BCL-2 expression and the length of survival of patients with glioblastomas or medulloblastomas. PMID- 7879599 TI - Dynamics of actin filaments in microglia during Fc receptor-mediated phagocytosis. AB - The phagocytic ability of mouse microglia during their differentiation in culture and after stimulation with bacterial wall lipopolysaccharide (LPS) has been investigated using Fc receptor-mediated phagocytosis of immunoglobulin (IgG) coated sheep erythrocytes (SRBCs). We observed that in 10-14 day-confluent neopallial cell cultures some immature microglia are not phagocytic but, on further culturing, they do become phagocytic. LPS-stimulated microglia are able to phagocytose larger numbers of IgG-coated SRBCs and at a faster rate than non stimulated microglia. Within 5-10 min of phagocytosis the actin filaments of the LPS-stimulated microglia become depolymerized, leaving only bundles of actin filaments around the phagocytosed SRBCs (phagosome cups). At 30 min after the start of phagocytosis the actin filaments of the LPS-stimulated microglia begin to polymerize, and within 2 h the original pre-phagocytosis pattern of the actin filament network is re-established. The non-LPS-stimulated microglia exhibit actin filament depolymerization in only a few lamellipodia and polymerization of actin filaments around engulfed particles, but much later during phagocytosis. PMID- 7879600 TI - Neuronal density in the superior frontal and temporal gyri does not correlate with the degree of human immunodeficiency virus-associated dementia. AB - Human immune deficiency virus (HIV) disease may be associated, neuropathologically, with significant neuronal loss and clinically with a severe dementia. However, the significance of neuronal loss in the development of dementia has not been established. In this study we have undertaken a stereological determination of the neuronal numerical density and neuronal volumes in post mortem tissue from the superior frontal and superior temporal gyri in 32 patients who died of acquired immune deficiency syndrome (AIDS). All were prospectively clinically characterized, with dementia identified or excluded, and antiretroviral medication documented. This study combines morphometric techniques with prospective clinical assessment of dementia. As previously demonstrated, all patients dying with AIDS showed neuronal loss, but this was not related to the presence of HIV-associated dementia. PMID- 7879601 TI - beta-Amyloid precursor protein isoforms show correlations with neurones but not with glia of demented subjects. AB - Post-mortem cerebral cortex from 15 demented patients was specially collected to minimise autolysis and two membrane fractions and one soluble fraction were quantitatively examined for the major species of beta-amyloid precursor protein (APP) of high apparent molecular mass (> or = 80 kDa) together with the major mRNA species encoding APP isoforms. The number of pyramidal neurones and astrocytes, putative biochemical indices of interneurones and pyramidal neurones, and choline acetyl transferase activity were also determined. Multiple regression analysis has been used to investigate intercorrelations of APP species with biochemical and morphometric measures, free of any effects of confounding demographic variables. Subjects with Alzheimer's disease showed a loss of cholinergic activity and D-aspartate uptake compared with patients with other causes of dementia. The major finding of the study is that measures of neurones rather than astrocytes most closely correlate with the concentration of APP. Pyramidal cell numbers were positively correlated with mRNA for APP695. APP in the soluble fraction showed a negative correlation with pyramidal cell numbers and cholinergic activity. These results indicate that neurones within the cerebral cortex are the major source of APP, and that secretion of APP is dependent upon cortical pyramidal neuronal activity and cholinergic activity. PMID- 7879602 TI - In vivo induction of the growth associated protein GAP43/B-50 in rat astrocytes following transient middle cerebral artery occlusion. AB - Immunohistochemistry was used to investigate the induction of growth-associated protein GAP43/B-50 in the astrocytes of rat cerebrum in vivo following ischemic injury produced by 30 min of transient middle cerebral artery occlusion. Three days after operation, GAP43 immunoreactivity first appeared in some astrocytic populations surrounding the infarcted lesion. Induction of GAP43 in those astrocytes persisted for up to 14 days and disappeared at 30 days postoperation. Double-immunofluorescence staining confirmed that the GAP43-immunoreactive astrocytes examined were all positive for glial fibrillary acidic protein. Our present data suggest that certain astrocytes could be induced to synthesize GAP43 in vivo in response to an ischemic insult in adult rats. PMID- 7879603 TI - Ciliary neurotrophic factor improves muscle fibre reinnervation after facial nerve crush in young rats. AB - In the present study we examined the effect of recombinant human ciliary neurotrophic factor (rH-CNTF) on muscle fibre reinnervation. After facial nerve crush, rats were treated systemically with either rH-CNTF (1 mg/kg per 48 h) or saline and were killed on days 10-13 after nerve crush when muscle fibre reinnervation becomes apparent. Blind counting of the number of reinnervated motor endplates and the length of the synaptophysin-positive staining was used to assess the effect of CNTF treatment on muscle fibre reinnervation in the whisker muscle. On day 10, both treatment groups showed a limited number of reinnervated motor endplates. Both the saline- and CNTF-treated rats showed a significant increase in the percentage of reinnervated motor endplates and in the length of the synaptophysin-positive staining with time. On days 10 and 11, there was no difference in muscle fibre reinnervation between the treated groups. On days 12 and 13, the CNTF-treated rats showed an increased muscle fibre reinnervation which was significant compared to the saline-treated rats. These results suggest that after facial nerve crush in young rats, CNTF enhances muscle fibre reinnervation, most probably by stimulating the intramuscular branching. There is no support for an effect of CNTF on nerve sprouting in the proximal axonal part or on axonal elongation; the CNTF effect on intramuscular branching might be mediated by the muscle fibres. PMID- 7879605 TI - Sciatic nerve morphology and morphometry in mature rats with streptozocin-induced diabetes. AB - Controversy exists as to the morphological and morphometric changes seen in experimental diabetic neuropathy (EDN). Most previous studies have utilized immature animals, with controversy as to whether the observed changes are due to maturational delays induced by hyperglycemia, or to diabetes per se. This study utilizes mature 9-month-old Sprague-Dawley rats. Six control and six hyperglycemic rats were examined 24 weeks after streptozocin injection. No morphological abnormalities were seen in the sciatic nerve at the light microscopy level. Total fascicular area and myelinated fiber density showed no significant differences (ANOVA, P > 0.05). No significant differences [ANOVA, P > 0.05 and Kolmogorov-Smirnoff (K-S), P > 0.05] between control and diabetic groups were shown for fiber, axon, and myelin areas, fiber and axon diameters, and myelin thickness. Fiber index of circularity, axon index of circularity, and g ratio were not significantly different with ANOVA (P > 0.05), but the diabetic group showed significantly lower values (P < 0.001) with K-S testing. Regression analyses of axonal area and log(n) axonal area plotted against myelin thickness showed no significant differences between the control and diabetic animals. This study in mature rats confirms the relative lack of morphological and morphometric changes in EDN which have previously been reported in studies involving immature rats. It highlights the difficulties in trying to extrapolate from EDN to human diabetic neuropathy where severe morphological and morphometric abnormalities may be present. PMID- 7879604 TI - Neurofibrillary tangle predominant form of senile dementia of Alzheimer type: a rare subtype in very old subjects. AB - In a consecutive autopsy series of 580 demented elderly subjects, 256 with the clinical diagnosis of probable/possible Alzheimer's disease (AD), there were 10 cases aged between 80 and 99 years with moderate to severe dementia or confusional state in which neuropathological studies revealed abundant neurofibrillary tangles with predominant involvement of the allocortex (entorhinal region, subiculum, CA 1 sector of hippocampus, amygdala) but no or only very few senile plaques. Small numbers of diffuse deposits of beta A4 amyloid protein were present in the entorhinal cortex of 3 and in the isocortex of 5 brains, while neuritic plaques were totally absent. Only a few cases of this "senile dementia with tangles only" or, more correctly, "neurofibrillary predominant type of AD" corresponding to the limbic stage of neuritic AD pathology have been described in the literature. This rare subtype occurring in very old (over 80 years of age) subjects that does not fall within the currently used neuropathological criteria for diagnosis of AD warrants further clinico pathological documentation. PMID- 7879606 TI - Leptomeningeal lipid storage patterns in Fabry disease. AB - We found two patterns of leptomeningeal storage that reflect two basic visceral storage patterns in Fabry disease. (i) A generalized-type leptomeningeal storage pattern, affecting all main leptomeningeal cell types (external arachnoideal epithelium, fibroblasts, vessel wall elements), was a consistent finding in three cases of classical generalized visceral phenotype. (ii) A localized leptomeningeal storage pattern was expressed, to a high degree, solely in the external arachnoidal epithelium; this pattern was found in one case with the variant visceral-restricted-type storage (confined to the cardiocytes). Thus, the external arachnoidal epithelium may be particularly susceptible to Fabry lipid storage, probably caused by a distinctly larger sustained lysosomal lipid load as compared to other cell types. PMID- 7879607 TI - Cadmium encephalopathy: a report with elemental analysis and pathological findings. AB - We report a boy of East Indian origin, aged 2 years and 10 months, who died suddenly and unexpectedly. Autopsy findings showed marked cerebral swelling with herniation and histological evidence of marked cerebral edema with perivascular protein leakage, indicating blood-brain barrier disruption. Energy dispersive X ray microprobe analysis of the brain demonstrated the presence of cadmium and a marked increase in sulfur, predominantly intracellular, both within neuroglial, and to a lesser degree endothelial, cells. Localization was predominantly in the nucleus. Analysis of the kidney showed cadmium deposition in renal tubules and in the basal lamina of podocytes within the glomerulus. Although the environmental source of cadmium remains unknown, we speculate that acute cadmium toxicity led to brain intracellular accumulation with resultant cellular dysfunction, blood brain barrier disruption, and lethal cerebral edema. PMID- 7879608 TI - Astrocytic straight tubules in the brain of a patient with Pick's disease. AB - This report concerns an immunohistochemical and ultrastructural study of cerebral astrocytes in a patient with Pick's disease of 20 years' duration. The autopsied brain was prominently small (710 g) with marked fronto-temporal lobar atrophy. Histological examination demonstrated profound neuronal loss and spongy changes with tau-positive Pick bodies in the frontal and temporal cortex. In addition, many glial cells in the temporal lobe white matter contained round to oval, argentophilic and slightly hematoxinophilic cytoplasmic inclusions that were also immunolabeled with the anti-tau antibody. On electron microscopy, the glial inclusions were observed in the perikarya of astrocytes that were recognized as such from intracytoplasmic glial filaments and the presence of gap junctions. The inclusions were free in the cytoplasm, without a limiting membrane, and mainly comprised irregular aggregations of bundles of about 15-nm straight tubules, which were indistinguishable from those of intraneuronal Pick bodies. Furthermore, various patterns of accumulation of the same straight tubules were frequently noted in perivascular astrocytic processes carrying a basal lamina. These findings indicate that in Pick's disease astrocytes are also affected by a similar insult to that which affects neurons. PMID- 7879609 TI - Unusual case of corticobasal degeneration with tau/Gallyas-positive neuronal and glial tangles. AB - A 74-year-old woman with corticobasal degeneration (CBD) had a 9-year history of progressive loss of strength and rigidity of her right hand and then arm, followed by speech difficulties, dyskinesia, rigidity, spasticity and weakness of the ipsilateral lower limb, ultimately also involving the opposite side. She later developed supranuclear gaze palsy. Her memory remained intact during most of the duration of her disease. Laboratory tests and anti-Parkinsonian medications were not helpful. At autopsy, frontal lobe atrophy, discoloration of putamen (Pt) and pallor of substantia nigra (Sn) were observed. Neuronal loss and gliosis were extensive in motor cortex and milder in frontal cortex, abruptly ending at the central sulcus and junction of cingulate gyrus. "Achromatic" neurons were present. Neuronal loss and gliosis were seen in Pt and Sn and corticobasal inclusions in Sn. Numerous Gallyas/tau-positive, Bielschowsky/ubiquitin-negative coil, sickle, or coma-shaped tangles and thread like processes were found in affected cortex, Pt and Sn. Some of the tangles were in neurons, but most occurred in astroglia, and their processes. The presence of Gallyas/tau-positive glia in CBD may have the same diagnostic significance as in progressive supranuclear palsy, analogous to the argyrophilic ubiquinated inclusions in oligodendroglia in multisystem atrophy. We suggest that in CBD: (1) cytoskeletal protein metabolism in neurons and glia can simultaneously be perturbed in certain neurodegenerative diseases, and (2) the astrocytosis in CBD may not be simply a reactive process but an integral part of the disease. PMID- 7879610 TI - Hippocampal sclerosis: a common pathological feature of dementia in very old humans. PMID- 7879611 TI - Senile plaques, "aging" and Alzheimer's disease. PMID- 7879612 TI - Nerve biopsy findings in Niemann-Pick type II (NPC) PMID- 7879613 TI - Vestibular findings associated with chronic noise induced hearing impairment. AB - Histological and functional derangements of the vestibular system have been reported in laboratory animals exposed to high levels of noise. However, clinical series describe contradictory results with regard to vestibular disturbances in industrial workers and military personnel suffering from noise induced hearing loss (NIHL). The purpose of the present study was to evaluate vestibular function in a group of subjects with documented NIHL, employing electronystagmography (ENG) and the smooth harmonic acceleration (SHA) test. Subjects were 22 men suffering from NIHL and 21 matched controls. Significantly lower vestibulo-ocular reflex gain (p = 0.05), and a tendency towards decreased caloric responses were found in the study group. No differences in the incidence of vertigo symptoms, spontaneous, positional and positioning nystagmus, directional preponderance and canal paresis in the ENG, or the SHA test phase and asymmetry parameters were observed between the groups. These results demonstrated a symmetrical centrally compensated decrease in the vestibular end organ response which is associated with the symmetrical hearing loss measured in the study group. Statistically significant correlations were found between the average hearing loss, the decrement in the average vestibulo-ocular reflex gain (p = 0.01), and ENG caloric lateralization (p = 0.02). These correlations might indicate a single mechanism for both cochlear and vestibular noise-induced injury. The results imply subclinical, well compensated malfunction of the vestibular system associated with NIHL. PMID- 7879614 TI - Temporal bone pathology in patients without caloric response. AB - Pathologies of serial sections of 9 temporal bones from 6 patients without caloric response were studied. The patients died of epipharyngeal cancer, middle ear cancer, chronic renal failure with DIC, pancreatic cancer with DIC, multiple brain metastasis of pancreatic cancer, and leukemia. Under light microscopy, 8 ears showed pathologies in the vestibular end organs and the nerves. Possible causes of the lack of caloric responses in the 8 ears were endolymphatic hemorrhage, labyrinthitis, leukemic infiltration in the labyrinth, degeneration or disappearance of the vestibular sensory cells, reduction in the number of vestibular nerve fibers, and/or brainstem lesions. The remaining one ear did not show abnormal findings in the vestibular end organs or the nerves, but the patient had brainstem lesions. Four types of temporal bone pathologies were observed according to the lesion site responsible for the lack of caloric response; i) sensory type, ii) neural type, iii) mixed type and iv) central type. PMID- 7879615 TI - 3DFT-magnetic resonance imaging of the inner ear in Meniere's disease. AB - Three dimensional Fourier transformation constructive interference in steady state (3DFT-CISS) magnetic resonance imaging (MRI) allows a detailed visualization of the membranous labyrinth of the inner ear. In this study the endolymphatic duct and sac is investigated in patients with Meniere's disease using 3DFT-CISS MRI. In addition, the distance between the vertical part of the posterior semicircular canal and the fossa posterior is quantified. PMID- 7879616 TI - Blood viscosity and plasma viscosity in patients with sudden deafness. AB - Blood viscosity and plasma viscosity were measured in 51 patients with sudden deafness (SD) and 70 controls with normal hearing. Blood viscosity and plasma viscosity in patients with SD at their first medical examination were significantly higher than in the control group. The difference in viscosimetry results between the two groups was greater at higher shear rates. The data obtained in viscosimetry and pure-tone audiometry were analyzed after dividing the patients into a high viscosity group and a normal viscosity group. The correlation between average hearing level in pure-tone audiogram and blood viscosity or plasma viscosity was positive. The values of the O2-transport capacity of the blood demonstrated a negative correlation with average hearing level in patients with SD before treatment. During the course of treatment, blood viscosity and plasma viscosity decreased with the improvement of hearing impairment. When the distribution of average hearing level was 40 to 79 dB, a few of the patients with "recovery" or "good improvement" and most of patients with "fair improvement" or "no change" belonged to the low viscosity group. And, most of the patients with flat type hearing impairment and a few patients with high tone type hearing impairment belonged to the high viscosity group. These results suggest that many patients with SD have increased blood viscosity and plasma viscosity, and that this increase may play a significant role in the etiology of SD. There are also some differences in etiologic factors concerning type of hearing impairment and prognosis. In conclusion, the present study points to the importance of measuring blood viscosity and plasma viscosity in patients with SD, since blood and/or plasma viscosity may be involved in its etiology and prognosis. PMID- 7879617 TI - Glutamate-induced intracellular Ca2+ elevation in isolated spiral ganglion cells of the guinea pig cochlea. AB - Intracellular calcium concentrations ([Ca2+]i) in acutely isolated spiral ganglion cells (SGCs) of the guinea pig cochlea were measured using digital imaging microscopy and the Ca(2+)-sensitive fluorescence dye fura-2. L-glutamate increased [Ca2+]i in SGCs with neuritic processes but did not lead to an increase in [Ca2+]i in SGCs without neuritic processes. The depolarization induced by high K+ (150 mM) solution increased [Ca2+]i in both SGCs, with and without neuritic processes. The L-glutamate-induced [Ca2+]i elevation was abolished in the absence of extracellular Ca2+. We thus propose that the increase of [Ca2+]i during L glutamate stimulation is mainly related to an influx of extracellular Ca2+. The excitatory amino acids, probably L-glutamate, may function as a neurotransmitter of the hair cell-afferent nerve synapse in the guinea pig cochlea. PMID- 7879618 TI - Fibronectin-like immunoreactivity of the basilar membrane of celloidin-embedded human temporal bone sections. AB - Dysfunction of the mechanical properties of the basilar membrane is a potential cause of presbycusis. In cases of minimal sensorineural or strial degeneration it is believed to play a major role. The membrane has been shown to be partly composed of fibronectin. Fibronectin immunoreactivity is diminished in aged rats. Mesothelial cell line the perilymphatic surface of the membrane and are reduced in number in the aged rat cochlea. Fibronectin immunoreactivity was examined in human temporal bone sections (6 months to 92 years old). Hematoxylin and eosin stained section (17 to 97 years) were immunoreactivity was demonstrable in the human cochlea, but was not reduced, even in the eldest cases examined The number of mesothelial cells was reduced, however, and was related to the age of the individual, but not to the clinical diagnosis or audiogram shape. These two factors do not, therefore, appear to give rise to hearing losses associated with presbycusis. PMID- 7879619 TI - Cochlear implantation in children: labyrinthitis following pneumococcal otitis media in unimplanted and implanted cat cochleas. AB - Pneumococcal otitis media is frequent in young children and could lead to labyrinthitis post-implantation. To assess the risk, and methods of minimizing it by a graft to the round window around the electrode entry point, we have used a cat animal model of pneumococcal otitis media. Twenty-one kittens were used in the study. Thirty-two cochleas were implanted when the kittens were 2 months of age. Fourteen cochleas were implanted without using a graft (12 were available for study); 9 had a fascial graft, and 9 a Gelfoam graft (7 were available for study). The implanted kittens had their bullae inoculated with Streptococcus pneumoniae 2 months after implantation and were sacrificed 1 week later. There were also 9 unimplanted control ears which were inoculated when the animals were 4 months of age. Labyrinthitis occurred in 44% of unimplanted control, 50% of implanted ungrafted, and 6% of implanted grafted (fascia and Gelfoam) cochleas. There was no statistically significant difference between the unimplanted control and the implanted cochleas (p < 0.05). There was, however, a difference between the implanted-ungrafted and implanted grafted cochleas, but not between the use of fascia and Gelfoam to graft the round window entry point. As a result, the data indicates that cochlear implantation does not increase the risk of labyrinthitis following pneumococcal otitis media, but it is desirable to use fascia as a graft to the round window around the electrode entry point. PMID- 7879620 TI - Effect of craniotomy and cerebrospinal fluid loss on the inner ear. An experimental study. AB - Craniotomy with cerebrospinal fluid (CSF) suction was performed on 18 guinea pigs to determine the effects on the inner ear morphology. Six control animals received anaesthesia only and 12 were operated on with a postoperative survival time of 1 or 24 h. The histologic examinations showed no signs of endolymphatic hydrops or injury to other structures in any of the animals. In 11 of the operated animals, red blood corpuscles were demonstrated in the perilymphatic space of the cochlea, the subarachnoid space, and the cochlear aqueduct (CA). After 1 h survival time blood had entered primarily the basal part of the scala tympani, but in the animals of 24 h survival time the blood was more abundant in both the scala tympani and the scala vestibuli indicating flow within the inner ear. The CA thus provides a pathway between the CSF and the whole of the perilymph through which noxious effects could take place. PMID- 7879621 TI - Identification of substances in the endolymphatic sac. AB - The composition of the contents of the endolymphatic sac (ES) has yet to be fully defined. Carbohydrates have been found in the ES of human fetuses and animals but not identified in the adult human ES. In the present study, celloidin was removed from previously prepared human temporal bone sections and a histochemical method was used to detect carbohydrates and protein in the ES. Six biotinylated lectins were used to identify specific carbohydrates in 15 ears: beta-D-N acetylglucosamine, beta-D-galactose, D-galactose, alpha-D-mannose, D-N acetylgalactosamine and alpha-L-fucose. The intensity of staining was graded qualitatively. A substance in the ES tubules that did not stain with any lectin was identified by the Millon reaction as containing protein. The carbohydrates and protein may exist in the different tubules or in the same tubule without mixing. This finding seems to support the idea that at least some of these substances are produced locally in the ES. Our observations support the hypothesis of the existence of a secretion and degradation system in the endolymphatic sac. PMID- 7879622 TI - Change in facial nerve innervation following hypoglossal-facial anastomosis. An animal study. AB - Hypoglossal-facial nerve anastomosis was carried out in 20 adult guinea pigs. Horseradish peroxidase (HRP) was applied to the buccal branch of the facial nerve at intervals of 2, 4 and 6 months after the anastomosis operation. HRP labeled neurons and the number of regenerated axons in the buccal branch were counted to determine postoperative nerve regeneration. The number of surviving neurons in the facial and hypoglossal nuclei was also counted to determine postoperative change of these nuclei. Following anastomosis, 97% of the hypoglossal neurons remained surviving, while the facial neurons underwent pronounced degeneration of 65% survival ratio at 2 months and 37% at 6 months after the anastomosis operation. In 80% of the animals, a new nerve bundle regenerated from the proximal stump of the facial nerve to the anastomotic trunk. A linear increase of HRP-labeled neurons in the facial and hypoglossal nuclei paralleled the increase of the axons in the buccal branch. The HRP-labeled neurons in the facial nucleus were demonstrated to have direct connection with the newly formed bundle and the facial mimetic muscles were dually innervated by both the hypoglossal and facial nerves. Although the present study design might not fully represent the clinical situation, possible advantages of hypoglossal-facial nerve anastomosis are discussed from the view of nerve regeneration. PMID- 7879623 TI - Assessment of the gas exchange function of the middle ear using nitrous oxide. A preliminary study. AB - A method for assessing the gas exchange through the middle ear (ME) mucosa using nitrous oxide is introduced. Increases in the ME pressure was determined by a tympanogram or a micropressure sensor inserted into the mastoid cavity during ear surgery under general anesthesia using 67% nitrous oxide, 33% oxygen, and sevoflurane on 30 normal ears, 12 ears with otitis media with effusion (OME), and 3 postoperative ears with chronic adhesive otitis media or cholesteatoma. All the 30 normal ears except one showed varying pressure increase, and an inverse correlation was observed between pressure increase and area of mastoid on radiographs. Pressure increase was observed in 6 (50%) ears with OME, and this finding correlated well with the presence or absence of air space in the ME on computed tomography images examined preoperatively, on ears which had ear surgery, the presence or absence of pressure increase correlated with the degree of previous surgical intervention on the mastoid. The rationale and possibility of clinical application of this method is discussed. PMID- 7879624 TI - Experimental studies of the resolution of acoustic rhinometry in vivo. AB - The ability of acoustic rhinometry to detect objects of defined size in nasal cavities has hitherto been investigated only in cadavers and models. We aimed to determine the resolution of the technique in the nose of living subjects. Silicone spheres of 3.0, 5.0, and 7.0 mm diameter were placed at two sites in the decongested and locally anaesthetised nasal cavities of 3 healthy adults. Acoustic rhinometry area-distance functions were obtained before and after insertion of the spheres, with further control data obtained after removal of the sphere from the nasal cavity. Six nasal cavities were studied in each test state on two separate occasions. The 3.0 mm sphere caused a statistically significant change in cavity volumes in only 17% of cases when placed in the middle meatus and in 8% at the nasal value (Mann-Whitney U-test; p < 0.05). The detection rates for the 5.0 mm sphere were 50% in the middle meatus and 50% at the nasal valve. When the control and test curves were compared by superimposition and the cross sectional areas at the site of perturbations compared statistically (Mann-Whitney U-test) the detection rates in the middle meatus were: 33%-3.0 mm and 67%-5.0 mm sphere. The detection rate at the nasal valve region was 25%-3.0 mm sphere and 58%-5.0 mm. The 7.0 mm sphere was detected in 100% cases by volume changes, and 80% by area changes. Acoustic rhinometry can reliably detect changes of volume and area in the living nose resulting from the introduction of a 7 mm sphere into the nasal valve or middle meatal region in most cases. Smaller spheres are detected in only a fraction of cases. The resolution of the technique is therefore close to 7.0 mm (1.44 cm3). These findings are important when interpreting acoustic rhinometry data in monitoring patients with nasal pathology. PMID- 7879625 TI - Radiologic assessment of diseased mucosa of the maxillary sinus after functional endoscopic sinus surgery. AB - We attempted to evaluate postoperative mucosal changes and symptomatic improvement in 99 patients who underwent functional endoscopic sinus surgery from September 1991 through August 1992. The patients were divided into 2-, 4-, 6-, and 12-month postoperative groups. Thickness of the maxillary sinus mucosa measured at the midpoint of the lateral sinus wall on a follow-up ostiomeatal unit computed tomogram (OMU CT) was compared with that of preoperative OMU CT. Postoperative endoscopic findings of the maxillary sinus and changes in presenting symptoms such as rhinorrhea, nasal obstruction, facial pain, headache, anosmia, epiphora, and referred otalgia were analyzed. Improvement in the diseased mucosa of the maxillary sinus, as evaluated on OMU CT, was observed in 69.7% of the patients, and such mucosal changes did not differ significantly among 2-, 4-, 6-, and 12-month follow-up groups. However, apparent mucosal changes exceeding marginal improvement was observed in 32.3% of the patients. The overall symptomatic improvement rate was 57.9% and improvement in endoscopic findings was observed in 46.3% of the patients. Although there was some discrepancy between radiologic and symptomatic improvement rates, symptomatic improvement was significantly related with radiologic improvement. It is suggested that removal of obstructive lesion in the ostiomeatal area might be beneficial in a seemingly early symptomatic improvement, but complete healing of the maxillary sinus mucosa as assessed by OMU CT might take longer than 12 months. PMID- 7879626 TI - Functional and phenotypic analysis of T-lymphocytes in laryngeal carcinoma. AB - We studied the functional response and phenotypic characterization of peripheral blood T cells and their correlation with the clinical stage of disease in 29 males with previously untreated carcinoma of the larynx and 24 healthy male controls. Peripheral blood T cells, phenotypically CD2+ CD3+, were significantly decreased in the patients relative to the controls. Patients with advanced locoregional extension (T4 and N1, 2, 3) also showed a diminution of the CD4+ subpopulation of T cells. DNA synthesis by purified T cells showed similar blastogenic responses in patients and controls; the interleukin-2 production of phytohemagglutinin stimulated lymphocytes was also normal. We conclude that in patients with laryngeal carcinoma there is a phenotypic alteration of the T cells that is variable according to tumor stage, without functional alterations in blastogenic capacity or IL-2 production. PMID- 7879627 TI - Extended supracricoid partial laryngectomy with tracheocricohyoidoepiglottopexy. AB - Extended supracricoid partial laryngectomy with tracheocricohyoidoepiglottopexy (TCHEP) was studied as an alternative to total laryngectomy in 16 patients with glottic carcinoma presenting a 10-15 mm of anterior subglottic extent. The technique of the procedure is described. Results were analyzed for tumor free margins, tracheostomy decannulation, oral alimentation, phonation and disease free interval. The 3-year survival and local control rate were 68% and 86.7%, respectively. Our preliminary data suggest that the TCHEP procedure is a viable alternative to total laryngectomy for patients presenting with varying degrees of carcinoma extension below the free edge of the true vocal cords. PMID- 7879628 TI - Indwelling tracheo-oesophageal voice prostheses post-laryngectomy in Sheffield, UK: a 6-year review. AB - The Groningen and Provox tracheo-oesophageal valve voice prostheses have been used in post-laryngectomy patients extensively in Sheffield since 1986 and 1990, respectively. To the present time a total of over 40 patients have made use of these devices, two thirds of whom underwent insertion at the time of laryngectomy. Prostheses were replaced under local or general anaesthesia if they were leaking or if phonation became increasingly difficult. Our experience with over 200 valves including the Groningen High Resistance, Groningen Low Resistance and Provox prostheses in this patient group is presented. We believe that the primary insertion of a low resistance prosthesis, either the Provox or Groningen Low Resistance device, is the method of choice in speech rehabilitation following laryngectomy. PMID- 7879629 TI - Middle ear transmission disorders by laser-Doppler vibrometry. PMID- 7879630 TI - Retinal vs. environmental orientation in the perception of the right angle. AB - The right angle is perceived as such only when its sides are vertical and horizontal (Goldmeier effect). We investigated if spontaneous verbal descriptions reflect this type of "oblique effect", and if the relevant frame of reference is retinal or environmental. We compared four conditions in which upright vs. tilted observers were asked to describe gravitationally normal vs. oblique angles. It is shown that the Goldmeier effect depends upon the environmental coordinates, which usually determine the orientation of the subjective frame of reference. We argue that the singularity of the right angle in the vertical/horizontal orientation depends on a phenomenological fact: only the normal right angle looks like a right angle. PMID- 7879631 TI - New perspectives on biological treatment of schizophrenia. AB - Recent research seems to indicate that many schizophrenics suffer from a defective brain development, which is reflected by basic disturbances in cognitive, information-processing, volitional and emotional functions. Positive symptoms like hallucinations and delusions may be secondary to the more basic disturbances. Varying degrees of defective brain development places a ceiling on the functional improvement that can be obtained in this illness. However, whereas positive symptoms usually respond best to neuroleptics, even negative symptoms can be improved, for instance by clozapine. To obtain such improvement, it seems necessary, in addition to blocking dopamine D2 receptors, to influence other receptor systems, as for instance serotonergic 5HT-2 and possibly dopaminergic D1 and/or D4 receptors. Stimulation of glutamatergic NMDA receptors also seems to be a promising possibility. PMID- 7879632 TI - Cognitive therapy with schizophrenic patients: conceptual basis, present state, future directions. AB - Schizophrenia may nowadays be most readily understood as a systemic disorder in which changes in the brain structure underlie individual cognitive abnormalities which for their part interact with environmental factors at the onset of the illness and during its course. From this, one may deduce the rationale for cognitive therapy for schizophrenic patients. Existing approaches may be systemised as direct, indirect and combined procedures. The latter are based on the assumption of the pervasive effects of elementary and complex cognitive dysfunctions at the levels of open behaviour. However, in a mirror-design study with 21 schizophrenic patients according to DSM-III-R in which the effects of various intervention sequences were examined, it was not possible to find confirmation for this. This and other open questions have led to doubts expressed in current literature concerning the utility of cognitive therapy, especially with respect to the locus, nature and malleability of cognitive disorders, as well as the possibility of generalizing cognitive improvements. The latter are discussed in detail and possible future directions in cognitive therapy for schizophrenic patients are shown. PMID- 7879633 TI - Changing cognitive functioning in rehabilitation of schizophrenia. AB - A three-factor model is proposed for clinical assessment of cognitive and neuropsychological impairments in schizophrenia. The first factor is stable, pervasive and vulnerability-linked. The second and third include executive, memory and conceptual abilities and are episode-linked. The third factor may be amendable to psychosocial treatment. PMID- 7879634 TI - The rationale for consultation with the families of schizophrenic patients. AB - Mental health professionals have approached families that have a schizophrenic member with four quite different expectations about how the family can aid patient recovery: the family as a source of information; the family as caretaker for the patient; the family as patient stressor, needing family education; and the family as a dysfunctional system requiring family therapy. Overall, professionals have been negligent in attending to the needs of families, seen less for themselves than as agents to aid patient recovery. As an alternative or supplement to family self-help groups, a family consultation model provides professionals with an orientation for working collaboratively with diverse families in their efforts to cope with serious mental illness. PMID- 7879635 TI - Stress reduction in the social environment of schizophrenic patients. AB - Patients with schizophrenia are sensitive to short term social stressors in the form of life events, and the long term stress of living with high Expressed Emotion (EE) relatives. A number of family interventions have been evaluated in controlled trials. A comparison of successful and unsuccessful interventions indicates the optimal type of intervention for patients in high EE environments. PMID- 7879636 TI - Empirical correction of seven myths about schizophrenia with implications for treatment. AB - This paper presents empirical evidence accumulated across the last two decades to challenge seven long-held myths in psychiatry about schizophrenia which impinge upon the perception and thus the treatment of patients. Such myths have been perpetuated across generations of trainees in each of the mental health disciplines. These myths limit the scope and effectiveness of treatments offered. These myths maintain the pessimism about outcome for these patients thus significantly reducing their opportunities for improvement and/or recovery. Counter evidence is provided with implications for new treatment strategies. PMID- 7879638 TI - Can psychoanalytic theory contribute to the understanding and treatment of schizophrenia? AB - A discontinuity between the study of the brain and study of the mind is discussed. Mental phenomena emerge from the level of individuals interacting through language. Mental life as based in interindividuality is nevertheless experienced solitary. Bion's notion of psychosis as a fantasy of omniscience taking over consciousness. Two clinical vignettes. PMID- 7879637 TI - What has become of the psychotherapy of schizophrenia? AB - The psychotherapy of schizophrenia has undergone major changes in the past two generations and mirrors larger paradigmatic shifts in thinking about severe mental illness and its treatment. Despite being endangered acutely by fiscal crises in our current health care systems, the psychotherapy of schizophrenia continues to evolve in a healthy manner as advances are made in our understanding of schizophrenia. PMID- 7879639 TI - Is the concept of schizophrenia useful from an aetiological point of view? A selective review of findings and paradoxes. AB - In this selective review of findings from aetiological schizophrenia research, attention is focused on problems of classification and paradoxical observations in family and twin research, as well as interesting findings from high risk studies. The author raises the question if our modern classification of the functional severe mental disorders hampers aetiological research. PMID- 7879640 TI - Schizophrenia epigenesis: past, present, and future. AB - Sociopolitical and ideological attacks on the various genetically oriented programs of research into the causes of schizophrenia, even when well-motivated to prevent genetic discrimination in all its forms, endangers the enterprise. Although there have been no replicated successes in finding genes linked or associated to markers for schizophrenia yet, the solid foundation for the fact that genetic factors are importantly involved in the etiology of schizophrenia derives from replicated studies using the strategies of genetic epidemiology- families, twins, adoptees. The models to emulate in schizophrenia research should follow the paths of researchers on coronary artery disease, diabetes, and Alzheimer's disease. All are complex diseases with multifactorial and multigenic components. Even when the necessary genotype is present, it may not be expressed as clinical disease at the phenotypic level. PMID- 7879641 TI - Searching for the phenotypes of schizophrenia. AB - Use of clinical diagnosis as the phenotype for genetic study is discussed, and criteria for appropriate alternative phenotypes are presented. Then, recent research on four alternatives is discussed: (a) resistance to interference from an associative prime, (b) reaction time crossover, (c) creativity, and (d) socioeconomic achievement. It is concluded that resistance to interference from an associative prime and reaction time crossover at 3-sec. preparatory interval level are the most promising of these candidates. PMID- 7879642 TI - Personality deviations within the schizophrenia spectrum. AB - The aim of this paper is to find out what kind of nonpsychotic personality features may have the same origin as schizophrenia and thus constitute a nonpsychotic alternative to schizophrenia. Family, twin and adoption studies are reviewed. The conclusion is that only schizotypal personality disorder seems to be etiologically related to schizophrenia. Among the schizotypal criteria, only eccentricity, affect constriction and excessive social anxiety are unequivically a nonpsychotic, etiologically linked alternative to schizophrenia. PMID- 7879643 TI - Biologic factors in schizotypal personal disorders. AB - New studies of the boundaries of schizophrenia suggest that schizotypal personality disorder is biologically and genetically related to schizophrenia with alterations in brain structure/function related to deficit-like symptoms and increased dopaminergic function to psychotic-like symptoms. PMID- 7879644 TI - Positive and negative symptoms of schizophrenia: past, present, and future. AB - The "group of schizophrenias," normally referred to with a single nominative, is phenomenologically heterogeneous. Its symptoms represent multiple psychological domains, including perception, inferential thinking, language, attention, social interaction, emotion expression, and volition. Studies of psychopathology have simplified this complex array in several ways; one has been a subdivision into positive and negative symptoms. Reports by our group and others suggest that the symptoms of schizophrenia fall into three natural dimensions: positive symptoms subdivided into psychotic and disorganized dimensions, while a third negative dimension also emerges. Since these dimensions have impressive consistency across studies, future work must examine their relationship to clinically relevant concepts such as prognosis or etiology and examine four different aspects: longitudinal course, neural mechanisms, relationship to treatment, and interrelationships in other pathological conditions. PMID- 7879645 TI - Intrafamilial relationships and the course of schizophrenia. AB - This paper describes efforts to explicate the significance of schizophrenic patients' sub-clinical psychopathology (SCP) to affective attitudes expressed by relatives about these patients. Using data from two 10-minute interactions between patients and close relatives (usually parents), verbal and non-verbal behaviors were scored for signs of SCP by the patient. Scores reflective of more overt signs of SCP were highly related to relatives' expressed emotion status and their affective style when interacting with the patient, suggesting that a complex transactional model best explains the connection between high EE status of a relative and the risk for patient relapse. PMID- 7879646 TI - Family interaction: parental representation in schizophrenic patients. AB - 12 monozygotic (MZ) and 19 same-sexed dizygotic (DZ) twin pairs discordant for DSM-III-R schizophrenia completed the Parental Bonding Instrument (PBI). The schizophrenic twins described their parents as less caring and being more overprotective compared to their non-schizophrenic co-twins. These results were independent of age, sex and zygosity. Difference in paternal overprotection was the most important variable discriminating between the schizophrenic probands and their co-twins. Three different hypotheses regarding these findings are discussed. PMID- 7879647 TI - Information-processing abnormalities as neuropsychological vulnerability indicators for schizophrenia. AB - Studies of schizophrenic patients in psychotic and clinically remitted states and of biological relatives indicate that subtle anomalies in information processing may be critical components of neuropsychological vulnerability to schizophrenia. We describe a conception of possible abnormalities and several recent strategies to differentiate these possibilities. Within Continuous Performance Test conditions, varying the perceptual load vs. the active, working memory load yields a distinction between a stable vulnerability factor across clinical states and a potential mediating vulnerability factor. Specialized backward masking paradigms offer ways to separate two initial sensory-perceptual processes from attentional shifting processes. Top-down attentional influences on sensorimotor gating allow examination of the role of central executive processes in modulating early sensory processes. Initial results are discussed. PMID- 7879648 TI - A cognitive model for schizophrenia and its possible neural basis. AB - It is proposed that the basic disturbance in schizophrenia corresponds to a disruption of the normal relationship between stored material and current sensory input. The link between information processing disturbances and their biological bases may be facilitated by the use of paradigms derived from animal learning theory. A model for the emergence of schizophrenic symptoms is presented. The core cognitive abnormality may result from a disturbance at any point in the neural circuit involved in the prediction of subsequent sensory input. PMID- 7879649 TI - Memory function in schizophrenia. AB - Memory impairment in schizophrenia has been reported in several studies during the last decades. Issues related to the interpretation of such deficits are discussed. Research strongly suggests specific memory dysfunction in schizophrenia that may be neither drug induced nor secondary consequences of attentional disorders. Our own longitudinal data indicate that these deficits deviate from normal function in a relatively stable way. Although medial temporal lobe structures seems to be of special importance, memory function may be vulnerable to a variety of neurobiological abnormalities. PMID- 7879650 TI - Cognitive dysfunctions and psychosocial treatment of schizophrenics: research of the past and perspectives on the future. AB - First, family research with the focus on the concept of communication deviance is reviewed. Then, the link between family factors and cognitive characteristics in the offspring is elaborated on. Research on cognitive dysfunctions with a basis in a vulnerability model is the theme of the next section. Finally, psychosocial and cognitive treatment programmes are outlined and discussed. PMID- 7879651 TI - Determination of horseradish peroxidase concentration using the chemiluminescence of Cypridina luciferin analogue, 2-methyl-6-(p-methoxyphenyl)-3,7 dihydroimidazo[1,2-a]pyrazin-3-one. AB - The chemiluminescence of the Cypridina luciferin analogue, 2-methyl-6-(p methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one (MCLA) was observed at 462 nm in the presence of horseradish peroxidase (HRP) and the total spectrum of light emitted was found to depend linearly on HRP concentration. Methods for the determination of HRP concentration using the chemiluminescence was investigated. HRP could be detected in the range from 100 pmol/L to 100 nmol/L under the optimum condition, H2O2 (10 mmol/L) and MCLA (10 mumol/L) at pH 5.8. PMID- 7879652 TI - Cytoplasmic factors that affect the intensity and stability of bioluminescence from firefly luciferase in living mammalian cells. AB - In order to improve calibration of firefly luciferase signals obtained by injecting the enzyme into single, isolated heart and liver cells we have investigated why the luminescence from cells is greatly depressed compared with in vitro (in mammalian ionic milieu) and why the decay of the intracellular signal is remarkably slow. We have shown that inorganic pyrophosphatase greatly depresses the signal in vitro and that micromolar concentrations of inorganic pyrophosphate, comparable with that in cytoplasm, reverse this inhibition and stabilize the signal, eliminating its decay. Higher concentrations of pyrophosphate depress the signal by inhibiting ATP-binding to luciferase. Luciferase-injected cells exposed to extracellular luciferin concentrations above about 100 mumol/l (corresponding to a cytoplasmic level of c. 5-10 mumol/l because of a transplasmalemmal gradient) show a gradual, irreversible loss of signal. We attribute this phenomenon (which is not seen in vitro) to the gradual accumulation of a luminescently inactive, irreversible, luciferase-oxyluciferin complex. At low luciferin levels this complex is prevented from forming by cytoplasmic pyrophosphate. Above c. 100 mumol/l extracellular luciferin, the pyrophosphate level in the cytoplasm fails to fully prevent the complex forming. In vitro this phenomenon does not occur because the luciferase concentrations and hence oxyluciferin levels are orders of magnitude lower than in cells injected with concentrated luciferase solutions, which have a cytoplasmic luciferase concentration of approximately 2-4 mumol/l. PMID- 7879653 TI - TCA-100 tumour chemosensitivity assay: differences in sensitivity between cultured tumour cell lines and clinical studies. AB - The BATLE LE TCA-100 tumour chemosensitivity assay has been used to evaluate chemotherapeutic drug sensitivity of cultured tumour cell lines. Studies were performed using test drug concentrations calibrated to discriminate sensitivity and resistance of clinical specimens. Strong sensitivity which appeared to be inconsistent with clinical experience was detected for some drugs and cell lines. Findings of strong sensitivity were consistent with basic differences between sensitivity testing cultured cell lines and clinical specimens. Results with cell lines frequently may not apply directly to clinical applications. Characterization of differences between cell lines and clinical specimens may assist in application of cell line findings to clinical trials. PMID- 7879654 TI - Bioluminescence and chemiluminescence literature. 1994 Literature: Part I. PMID- 7879655 TI - Interactions between papillomavirus proteins and tumor suppressor gene products. PMID- 7879656 TI - Activation of the Src family of tyrosine kinases in mammary tumorigenesis. PMID- 7879657 TI - Oncogenic properties of the middle T antigens of polyomaviruses. PMID- 7879658 TI - Selective involvement of protein kinase C isozymes in differentiation and neoplastic transformation. PMID- 7879659 TI - Fc gamma receptors in malignancies: friends or enemies? PMID- 7879660 TI - Dissecting molecular carcinogenesis: development of transgenic mouse models by epidermal gene targeting. PMID- 7879661 TI - The retinoblastoma tumor suppressor protein. PMID- 7879662 TI - Genetics in the thirties. PMID- 7879663 TI - From the melanocyte to melanoma to tumor biology. PMID- 7879664 TI - The origins of the small DNA tumor viruses. PMID- 7879665 TI - Retroviruses and wild mice: an historical and personal perspective. PMID- 7879667 TI - Sol Spiegelman. PMID- 7879666 TI - Historical origins of current concepts of carcinogenesis. AB - The first attempts to understand the causes of cancer were based on generalizations of what might now be termed a "holistic" nature, and hereditary influences were recognized at an early stage; these views survive principally through a supposed positive connection between psychological factors such as stress and diminished ability to combat the progressive development of tumors through some form of immunologically mediated rejection of potentially cancerous cells. While evidence for immunosurveillance is generally accepted, it is now widely regarded as almost wholly confined to instances where tumor viruses are involved as causative agents. The earliest theorists drew an analogy between the processes of carcinogenesis and of evolution; the cancer cells acquired the ability to outstrip their normal counterparts in their capacity for proliferation. This was even before evolution had been interpreted as involving a continuous succession of mutations. Evidence was already to hand before the end of the 18th century that exogenous agents, notably soot, a product of the "industrial revolution," could cause skin cancer. Somewhat over 100 years later, another industrial innovation, the manufacture of synthetic dyestuffs, implicated specific chemical compounds that could act systemically to cause bladder cancer. Meanwhile, the 19th century saw the establishment of the fundamentals of modern medical science; of particular relevance to cancer was the demonstration that it involved abnormalities in the process of cell division. The commencement of the 20th century was marked by a rediscovery of the concept of mutation; and it was proposed that cancer originated through uncontrolled division of somatically mutated cells. At around this time, two further important exogenous causative agents were discovered: X-rays and tumor viruses. In the late 1920s, x-radiation became the first established exogenous cause of mutagenesis. The discoverer of this phenomenon, H. J. Muller, suggested that while mutation in a single cell was the primary causative mechanism in carcinogenesis, its generally observed logarithmic increase in incidence with age reflected a "multihit" process, and that multiple successive mutations were required in the progeny of the original mutants. He also recognized that the rate of proliferation of potentially cancerous cells would markedly influence the probability of their subsequent mutation. These considerations are essentially the foundation of the generally accepted view of carcinogenesis that now seems unlikely to be superseded. However, this acceptance did not come about unopposed. The analogy between carcinogenesis and evolution was disliked by many biologists because it embodied the concept that cancer was an inevitable consequence of our evolutionary origins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7879668 TI - Growth dysregulation in cancer cells. PMID- 7879669 TI - Approaches for the optimization of experimental parameters in capillary zone electrophoresis. PMID- 7879670 TI - Multidrug resistance in the laboratory and clinic. AB - Multidrug resistance represents a major obstacle in the successful therapy of neoplastic diseases. Studies have demonstrated that this form of drug resistance occurs in cultured tumor cell lines as well as in human cancers. P-glycoprotein appears to play an important role in such cells by acting as an energy-dependent efflux pump to remove various natural-product drugs from the cell before they have a chance to exert their cytotoxic effects. Using the tools of molecular biology, studies are beginning to reveal the true incidence of multidrug resistance, as mediated by the MDR1 gene, in the clinical setting. It has been demonstrated, at least in the laboratory, that resistance mediated by P glycoprotein may be modulated by a wide variety of compounds, including verapamil and cyclosporine A. These are compounds which, by themselves, generally have little or no effect on the tumor cells, but when used in conjunction with antineoplastic agents act to decrease, and in some instances eliminate, drug resistance. The mechanism(s) by which these agents act to reverse resistance is not fully understood. Clinical trials to modulate P-glycoprotein activity are now under way to determine whether such strategies will be feasible. The detection of the P-glycoprotein in patient samples is very important in the design of these studies, as it appears that drug-resistant cells lacking P-glycoprotein will be unaffected by agents such as verapamil. Clinical studies are needed in which patients are stratified into chemotherapy protocols based on levels of MDR1 mRNA or P-glycoprotein expression in the primary tumors. Several research areas have been identified that are important to the transfer of the discovery of the MDR1 gene and its protein product from the research laboratory to the clinical environment. There is an immediate need for comprehensive information on the prevalence and levels of expression of the human MDR genes and their protein products in human organs and tissues. Data are needed on P-glycoprotein levels in specific subpopulations (e.g., according to age, sex, race, and diet), and the study of the heterogeneity and variability of expression of P-glycoprotein in normal human tissues should be given high priority. Since early studies have indicated some successes in identifying patients with classic multidrug resistance who might be responsive to chemosensitization, it can be anticipated that clinical research will accelerate in this area. The next wave of clinical studies will provide clinical investigators with opportunities to develop and evaluate P-glycoprotein tests and correlate test results with clinical outcomes. PMID- 7879671 TI - The gonadotropin surge in human reproduction: endocrine and biochemical mechanisms. PMID- 7879672 TI - Apoptosis and programmed cell death in health and disease. PMID- 7879673 TI - Immunosensors for clinical analysis. PMID- 7879675 TI - The management of penetrating abdominal trauma. PMID- 7879674 TI - Clinical significance of cardiac contractile proteins for the diagnosis of myocardial injury. PMID- 7879676 TI - The management of metastatic carcinoma in the liver. PMID- 7879679 TI - Current management of thyroid cancer. PMID- 7879678 TI - Pharyngoesophageal (Zenker's) diverticulum. PMID- 7879677 TI - Current status of resuscitation: solutions including hypertonic saline. PMID- 7879680 TI - Immunotherapy and gene therapy of cancer. PMID- 7879681 TI - Ileoanal anastomosis for inflammatory and noninflammatory bowel disease. PMID- 7879682 TI - The current management of common duct stones. PMID- 7879683 TI - Preoperative evaluation of cardiac risk. PMID- 7879684 TI - Surgical management of gastrointestinal carcinoid tumors. AB - While carcinoid tumors of the gastrointestinal tract continue to intrigue physicians and surgeons, the medical and surgical management of these tumors continues to evolve. Summarizing the current literature, patients should undergo local excision for incidental tumors of the stomach, rectum, and appendix, provided the tumor measures less than 2 cm in greatest dimension and does not demonstrate muscular invasion or lymph node metastases. Curative radical resection should be attempted, even in the presence of hepatic metastases, in patients with symptomatic or incidentally discovered carcinoid tumors of the small intestine, or in patients with large (> 2 cm) or invasive tumors. Palliative radical resection should be performed for patients with metastatic carcinoid tumors in light of the indolent tumor growth characteristics and the incapacitating symptoms related to tumor bulk and hormone production. Liver dearterialization should be considered only if resection cannot be safely accomplished. Carcinoid heart disease can be safely managed surgically and early intervention prior to the development of irreversible myocardial dysfunction is advocated. Medical therapy, primarily octreotide, should be offered to patients with disseminated tumors, and should be administered and available during the perioperative period to patients undergoing resection or liver dearterialization. With the use of new radioimmunoimaging techniques, earlier diagnosis, improved follow-up, and potentially targeted chemotherapy will be possible. As is evident, the treatment for gastrointestinal carcinoid tumors can be simple, as with small appendiceal tumors, or complex, as with disseminated small intestinal tumors. All surgeons should be familiar with the treatment options for these patients, as most can be treated by simple endoscopic excision or appendectomy. For the unusual patient with a disseminated carcinoid tumor, a multidisciplinary approach is required, combining the expertise of surgeons, oncologists, anesthesiologists, and radiologists for effective results. PMID- 7879685 TI - Current management of chronic pancreatitis. PMID- 7879686 TI - Workup of a patient with a mass in the neck. PMID- 7879687 TI - The multimodality treatment of esophageal cancer. PMID- 7879688 TI - Chronic intestinal pseudo-obstruction. PMID- 7879689 TI - The laparoscopic management of gastroesophageal reflux disease. PMID- 7879690 TI - Vascular trauma. PMID- 7879692 TI - The current management of acute pancreatitis. PMID- 7879691 TI - Blood administration, risks, and substitutes. PMID- 7879693 TI - [Ca2+]i-transients and actin polymerization in human neutrophils under stimulation with GRO alpha and complement fragment C5a. AB - The neutrophil chemotaxins, complement fragment C5a (C5a) and GRO alpha, induced the mobilization of Ca2+ from intracellular stores and the polymerization of actin in human neutrophils as assayed by flow cytometric measurements. [Ca2+]i transients developed as an "all-or-none" response. Individual neutrophils required different threshold concentrations of added ligand to induce [Ca2+]i transients which were then always maximal. In contrast, chemotaxin-induced formation of actin filaments in single neutrophils occurred in a dose-dependent manner. Pertussis toxin blocked chemotaxin-induced actin polymerization and [Ca2+]i-transients indicating that both cell responses shared initial activation steps such as ligand binding and activation of guanine nucleotide-binding proteins (G-proteins). PMID- 7879694 TI - In vitro and in vivo impact of a new glycosphingolipid on neutrophils. AB - A new water-soluble, orally absorbable de-N-acetyl-lysoganglioside (WILD20), breakdown product of the monosialoganglioside GM1, was found to influence some parameters of neutrophil response to inflammation stimuli. Superoxide anion production appears inhibited, along with neutrophil killing properties. A block of both pathways of arachidonic acid cascade and PAF was also found, as well as neutrophil ICAM-1-mediated adhesion to endothelial cells. Of particular interest was the significant reduction of neutrophils observed at the site of inflammation, whichever agonist was used. The effects on neutrophil physiology found in normal or in pathological conditions, are in favour of a WILD20-related inhibitory effect on neutrophil contribution to inflammation. PMID- 7879695 TI - Anti-inflammatory and antipyretic effects of boldine. AB - Boldine, an antioxidant alkaloid isolated from Peumus boldus, exhibits a dose dependent anti-inflammatory activity in the carrageenan-induced guinea pig paw edema test with an oral ED50 of 34 mg/kg. Boldine also reduces bacterial pyrogen induced hyperthermia in rabbits to an extent which varied between 51% and 98% at a dose of 60 mg/kg p.o. In vitro studies carried out in rat aortal rings revealed that boldine is an effective inhibitor of prostaglandin biosynthesis, promoting 53% inhibition at 75 microM. The latter in vitro effect may be mechanistically linked to the anti-inflammatory and antipyretic effects of boldine exerted in vivo. PMID- 7879696 TI - Effects of fepradinol on rat acute models of vascular permeability and leucocyte migration. AB - The antiinflammatory compound fepradinol has been tested in several experimental models of acute inflammation in rats. On the increased vascular permeability in the skin, fepradinol (25 mg/kg p.o.) was the only compound that inhibited the inflammatory actions induced by the three chemical mediators injected (histamine, serotonin and bradykinin). On the carrageenin-induced pleurisy, fepradinol (100 mg/kg p.o.) was more potent than indomethacin (5 mg/kg p.o.) and similar to piroxicam (5 mg/kg p.o.) in reducing the exudate volume and preventing cell migration. On the zymosan-induced peritonitis, while the activity of indomethacin (10 mg/kg p.o.) and cyproheptadine was observed only 3 h after zymosan challenge, the response of fepradinol developed within 30 min, suggesting that fepradinol inhibits both the early and late phases of the exudative response. These findings indicate that fepradinol may act on acute inflammation by reducing vascular permeability. PMID- 7879697 TI - Anti-inflammatory activity of the isoquinoline alkaloid, tetrandrine, against established adjuvant arthritis in rats. AB - Two isoquinoline plant alkaloids, tetrandrine (1) and berbamine (2), have been evaluated for anti-inflammatory activity in an acute paw oedema assay and in adjuvant-induced arthritis in rats. 1 but not 2 suppressed the chronic inflammation in the arthritis model but neither compound was active in the acute inflammation assay. In the adjuvant-induced polyarthritis, 1 was not effective when given at the time of inoculation (Day 0), nor just before (Day 7-10) signs of arthritis were evident. However, when given on a therapeutic dose schedule (Days 10-13) or continually (Day -1 to +14) on a prophylactic schedule, signs of arthritis including weight loss due to cachexia were significantly reduced. Given orally, 1 was considerably more potent than aspirin but not gastro-irritant and may be a promising lead for the development of a safe and effective treatment of chronic inflammatory diseases. PMID- 7879698 TI - TCV-309, a novel platelet activating factor antagonist, inhibits leukocyte accumulation and protects against splanchnic artery occlusion shock. AB - The aim of this study was to evaluate: (1) the accumulation of leukocytes in the ileum and the lung during splanchnic artery occlusion (SAO) shock; (2) the role of platelet-activating factor (PAF) and tumor necrosis factor (TNF-alpha) in this phenomenon. Untreated anesthesized rats subjected to total occlusion of the celiac, superior and inferior mesenteric arteries for 45 min, followed by reperfusion, uniformly died within 90 min after reperfusion. The mean survival time was 93 +/- 7 min. The neutrophilic infiltrate was quantitated in the ileum and in the lung using a myeloperoxidase (MPO) assay. MPO activity in the ileum and in the lung averaged 0.05 +/- 0.03 and 0.4 +/- 0.02 U x 10(-3)/g protein in animals killed before occlusion. MPO activity did not change in rats killed immediately before reperfusion and was significantly elevated (0.11 +/- 0.02 and 1.7 +/- 0.6 U x 10(-3)/g protein in the ileum and the lung, respectively) in those killed 80 min after the beginning of the reperfusion. The histological examination confirmed the accumulation of leukocytes in the mucosa of the ileum and the lung over the 80 min. SAO shocked rats exhibited leukopenia and increased serum levels of TNF-alpha. In order to evaluate the role of PAF and TNF-alpha in SAO shock, a powerful PAF receptor antagonist, TCV-309 (5 micrograms/kg i.v.), was injected 5 min after reperfusion. TCV-309 increased survival time, lowered serum TNF-alpha, reduced MPO activity in both the ileum and the lung and ameliorated leukopenia induced by SAO shock.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879699 TI - Bradykinin modulates mucin secretion but not synthesis from an intestinal goblet cell line. AB - The effect of the inflammatory mediator bradykinin on glycoprotein synthesis and mucin secretion in the human colonic adenocarcinoma cell line HT29-18N2 was examined. Bradykinin, at a threshold of 0.01 microM, accelerated the rate of mucin discharge as assessed by a mucin-specific ELISA. Using immunofluorescence microscopy, a thick meshwork of extracellular mucus was observed over bradykinin treated monolayers but not mock-treated controls. Morphometric analysis of bradykinin-treated monolayers revealed no decreases in intracellular mucin stores or any other easily discernable morphological alteration. The ability of the cyclooxygenase inhibitors indomethacin and naproxen to decrease the response to bradykinin by approximately 68% indicates the effect is mediated, at least partially, through the generation of prostaglandins. Bradykinin did not alter the rate of incorporation of 3H-glucosamine into newly synthesized glycoproteins. Bradykinin-accelerated mucin secretion may be linked to the depletion of intracellular mucin stores in the inflammatory bowel disease ulcerative colitis. PMID- 7879700 TI - The gastric cytoprotective action of adenosine and prostaglandin E2 in rabbits. AB - The direct protective action of adenosine and prostaglandin E2 (PGE2) was examined in an isolated gastric gland preparation in rabbits. Ethanol (8%, v/v) incubation markedly increased the release of lactate dehydrogenase (LDH) and number of non-viable glands in the preparation. Both effects were prevented by PGE2 preincubation in a concentration (10(-6), 1.4 x 10(-5) or 2.8 x 10(-5) M) dependent manner. The protective action was smaller in adenosine-treated groups, and yet the highest concentration (10(-4) M) of the compound also significantly inhibited the cytotoxic effects of ethanol. These findings indicate that both adenosine and PGE2 possess cytoprotective action on gastric glands in rabbits, but the former compound exerts its action beyond physiological concentrations. It is concluded that endogenous PGE2, but not adenosine may act as an ulcer modulator in the stomach. PMID- 7879701 TI - Gastric and duodenal anti-ulcer activity of sulpiride, a dopamine D2 receptor antagonist, in rats. AB - The gastric and duodenal anti-ulcer activity of sulpiride, a dopamine D2 receptor antagonist, was studied on various types of experimentally induced ulcers in rats, viz., pylorus ligation and water immersion + restraint stress-induced gastric ulcers, gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs and reserpine, and duodenal ulcers induced by cysteamine hydrochloride. It has been found to possess significant anti-ulcer activity against all these models. In 19 h pylorus ligated rats, it significantly reduced the gastric secretion, increased the fucose and sialic acid concentration of the gastric juice and reduced its protein content, thus increasing the total carbohydrate:protein (TC/PR) ratio. These results suggest that the antisecretory and gastric mucosal barrier strengthening effects of sulpiride may be responsible for its anti-ulcer activity. A central component also appears to be involved in its anti-ulcer action against water immersion + restraint stress model. The results of this study provide a rationale for its beneficial effect seen in the therapy of peptic ulcer disease. PMID- 7879702 TI - Stimulation and release of interleukin-1 from peritoneal macrophages of the mouse. AB - Lipopolysaccharide (LPS) caused a concentration-dependent increase of released and cell-associated interleukin-1 (IL-1) in resident peritoneal macrophages from the mouse. LPS was about 30 times more potent at stimulating the level of cell associated IL-1 than it was at stimulating the release of IL-1. Human recombinant tumour necrosis factor-alpha (TNF-alpha) and the calcium ionophores A23187 and ionomycin induced a concentration-dependent increase of cell-associated IL-1 but failed to cause release of IL-1 at concentrations producing maximal stimulation of cell-associated IL-1. The phorbol ester, 4 beta-phorbol dibutyrate, stimulated the release of IL-1 from mouse macrophages but failed to induce an increase in cell-associated IL-1. Substance P, neurokinin A, neurokinin B, calcitonin gene related peptide and platelet-activating factor did not increase the released or cell-associated IL-1 in mouse macrophages. These agents also failed to alter released or cell-associated IL-1 stimulated by LPS, 1 microgram ml-1. It appears that a calcium signal is sufficient for the transcription and translation of IL-1 mRNA but does not result in the secretion of biologically active forms of IL-1. Our data also indicate that different intracellular signals may control the release and the cell accumulation of IL-1. We conclude that inflammatory mediators may independently increase either the release of, or the cell accumulation of IL-1. PMID- 7879703 TI - Human atherosclerotic abdominal aortic aneurysms produce interleukin (IL)-6 and interferon-gamma but not IL-2 and IL-4: the possible role for IL-6 and interferon gamma in vascular inflammation. AB - Immunological mechanisms play an important role in the pathogenesis of atherosclerosis and atherosclerotic abdominal aortic aneurysms (AAA). Inflammatory leukocytes invade the vessel wall and produce cytokines which perpetuate the immune events underlying these diseases. Interleukin (IL)-1 beta, IL-8, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1, among others, may play a role in the generation by AAA. The aim of this study was to investigate the possible pathogenetic role of other proinflammatory cytokines, namely IL-2, IL-4, IL-6, and interferon (IFN)-gamma. Enzyme-linked immunosorbent assay of human explant culture supernatants revealed a significant increase in IFN-gamma production by AAA compared to occlusive (atherosclerotic) or normal (NL) aortic explants. IL-6 production was also increased in AAA compared to NL aortic explant supernatants. Neither AAA nor NL aortic tissues produced IL-2 or IL-4 in the same culture system. These results suggest that IL-6, a cytokine involved in T and B lymphocyte activation during inflammation, and IFN-gamma, which stimulates T and B lymphocytes, macrophages, endothelial cells and fibroblasts, may play a role in the pathogenesis of various vascular inflammatory diseases such as AAA. PMID- 7879704 TI - Immune-related edemagenic activity of glutamines and glutamic acid, components of immunomodulatory agents. AB - A number of compounds, in their structure similar to the immunomodulatory agent adamantylamide-L-alanyl-D-isoglutamine (AdDP), a desmuramyl analog of muramyl dipeptide (MDP), were compared with respect to their in vivo immunobiological activity. The agents were represented by adamantylamide-peptides or -amino acids differing principally in the nature of glutaminyl moieties. They were all able to induce inflammatory reaction which was prevented by anti-T-cell (TH) mAb, silica, indomethacin and dexamethasone. Responsible for this effect proved to be glutaminyl moieties (glutamine, isoglutamine, or glutamic acid), irrespective of their stereospecificity. Unlike the immunomodulatory molecule of AdDP, neither of the compounds and amino acids were able to stimulate production of antibodies in immunized animals, however. PMID- 7879706 TI - Pharmacological management of chronic pain: a clinician's perspective. AB - Of the currently available mu agonist drugs, the following are relatively contraindicated: 1. Methadone--unpredictable duration of action [5]. 2. Pethidine -unwanted central effects, metabolised to an active metabolite and too short acting. 3. Codeine--too weak and with constipating side-effects. 4. Fentanyl--too short acting. 5. Oxycodone--too short acting although suppositories may overcome some theoretical disadvantages. 6. Dextropropoxyphene--weak agonist which is possibly metabolised to a cardiotoxic metabolite [6]. Morphine remains the drug of choice for chronic pain when administered in a sustained release preparation. MS Contin, a slow release oral formulation of morphine, is available and has a predictable duration of action lasting from 8-12 h, while improved formulations are about to be released in the near future in some countries. Prescribers need to take into account the relatively poor oral bioavailability of morphine when calculating the daily morphine dose. PMID- 7879705 TI - Leflunomide: inhibition of S-antigen induced autoimmune uveitis in Lewis rats. AB - Leflunomide (LEF) is a novel immunomodulator which has been reported to be efficacious in experimental models of systemic autoimmune diseases and in treating rheumatoid arthritis in man. Leflunomide's ability to ameliorate ocular disease processes was investigated in a model of autoimmune eye disease, experimental autoimmune uveitis (EAU). EAU was induced by the injection of retinal S-antigen (S-Ag) into the foot-pad of Lewis rats. Leflunomide, or the reference compound cyclosporin A (CSA), was administered orally or topically (to one eye) each day beginning on the day of S-Ag injection. Drug efficacy was measured by the suppression in clinical signs of ocular inflammation and confirmed by histology. Both oral and topical ocular treatment with LEF suppressed the ocular disease signs and symptoms and retinal necrosis and reduced the S-Ag antibody levels associated with EAU in a dose-dependent manner. Both LEF and CSA were able to inhibit totally the disease manifestations of EAU; however, a comparison of the IC50 and IC90 values indicate that LEF is more potent than CSA in inhibiting EAU. These results suggest that leflunomide may be useful for treating autoimmune diseases of the eye. PMID- 7879709 TI - The analysis of virus-caused alterations of cellular and humoral immunoresponsiveness during the first days of morbilli rush in the young adult population. AB - The parameters of cellular and humoral immune responsiveness were studied during the first days of morbilli rush in the group of 34 young adult patients. The analysis of cell-mediated immune response included T cell relative and absolute numbers, mitogen-induced T cell proliferative response, as well as the relative and absolute numbers of mononuclear phagocytes. The tested parameters of humoral immune response included B cell relative and absolute numbers, serum concentrations of immunoglobulins IgG, IgA and IgM, and serum level of immune complexes (IC). The reduction of total leukocyte number, T cell and B cell relative and absolute numbers, as well as diminished mitogen-induced T cell proliferative response, associated with the elevation of IgM and IC serum levels were found in the majority of analyzed patients. Moreover, the subsequent analysis revealed positive correlations between T cell percentage and T cell proliferative response, as well as between serum concentrations of IgM and IC. These data confirmed the presence of acute morbilli infection-caused disturbances of patients' immunocompetence. PMID- 7879707 TI - Histamine increases anti-CD3 induced IL-5 production of TH2-type T cells via histamine H2-receptors. AB - Besides its proinflammatory functions histamine released from basophils and mast cells during immediate-type hypersensitivity reactions is known to inhibit several lymphocyte functions like IL-2 and gamma-IFN production. Recently, it has been shown that T helper cells of type 2 phenotype (TH2) represent the T cell fraction which may play a pivotal role in the promotion of the allergic inflammatory eosinophilic late-phase reaction by secretion of cytokines, especially IL-4 and IL-5. We have investigated the effect of histamine on anti CD3 induced IL-4 and IL-5 production by TH2 cells. Histamine in concentrations between 10(-7) and 10(-5) mol/l concentration-dependently increased anti-CD3 induced IL-5 production up to 120%, whereas IL-4 production was not affected. The activity of histamine in increasing IL-5 production was mimicked by the H2 receptor agonist dimaprit. Histamine induced increase in IL-5 production was inhibited by histamine H2-receptor antagonists, but remained unaffected by H1- or H3-receptor antagonists. Administration of forskolin which directly stimulates the production of cAMP, the second messenger of the H2-receptor, also resulted in an increase in anti-CD3 induced IL-5 production. These results indicate that the histamine-mediated increase in anti-CD3 induced IL-5 production is mediated via H2-receptors. Consequently, histamine released from mast cells and basophils during the early-phase allergic reaction may act as an important stimulatory signal for the initiation of the allergic inflammatory late-phase reaction by increasing local IL-5 production of allergen triggered TH2 cells. PMID- 7879708 TI - Presynaptic histamine H2 receptors modulate the sympathetic nerve transmission in the isolated rat vas deferens; no role for H3-receptors. AB - The modulatory activity mediated by histamine receptors on the sympathetic nerve transmission was investigated in the rat vas deferens. Agonists and antagonists acting at the different histamine receptor subtypes (H1, H2 and H3) were tested on electrically-driven preparations in vitro. Low-frequency stimulation (0.1 Hz) evoked muscle contractions almost completely-sustained by ATP release, while at high-frequency stimulation (5-10 Hz) norepinephrine was mainly involved. The H1 receptor agonists, pyridilethylamine and 2-(2 aminoethyl)thiazole, enhanced the electrically evoked twitch responses, but not contractions induced by exogenously applied norepinephrine and ATP. These effects were prevented by the H1-blocking drugs, mepyramine and phenyramine, but only at high concentrations (10 mumol/l). All these H1-antagonists strongly enhanced muscle response to electrical stimulation. The H2 receptor agonists, dimaprit, amthamine and impromidine, reduced the contractions evoked by field stimulation, but not by exogenously applied norepinephrine and ATP, the effect being antagonised by H2-blocking drugs, ranitidine and famotidine. The H3 receptor agonist, R(alpha) methylhistamine, reduced the electrically evoked muscle contractions, the effect being not modified by the selective H3-blocking drug, thioperamide, but prevented by famotidine. These data suggest that rat vas deferens contains presynaptic histamine H2 receptors, able to mediate inhibitory effects on the sympathetic transmission, while histamine H3 receptors are apparently not involved. On the contrary, the role of H1 is still unclear, since both agonists and antagonists may have the same effects. PMID- 7879710 TI - Seventeen years of application of herpes vaccines in Bulgaria. AB - This study reports on our experience with whole herpes simplex vaccines in Bulgaria for a period of 17 years. More than 1,500 immunized patients with herpes ophtalmicus showed a reduction of the recovery period, reduced number of the recurrences and reduced risk of visual damage. More than 14,000 patients suffering from other forms of herpes diseases for a longer period showed reduced recovery period and recurrence frequency in over 95% of the cases. Whole vaccines were well tolerable with no side effects. This report emphasizes the usefulness of whole herpes vaccines. PMID- 7879711 TI - Comparison of various methods of lipopolysaccharide isolation from Coxiella burnetii strain Priscilla in the virulent phase I. AB - Four methods of isolation of a lipopolysaccharide (LPS) from Coxiella burnetii strain Priscilla in virulent phase I have been examined. Each isolation method afforded a specific LPS portion of the polydisperse LPS system present in the outer membrane of C. burnetii cell. The hot phenol/water method was found the most efficient with respect to yield and chemical composition of the smooth (S) LPS that was shown to prevail in the outer membrane LPS macromolecules of C. burnetii. PMID- 7879712 TI - Characterization and sequence analysis of the F2 promoter from corynephage BFK20. AB - F2 promoter from corynephage BFK20 was isolated and characterized. It was functional in Escherichia coli and Corynebacterium glutamicum. Cloning of the F2 promoter into the pJUP05 promoter probe vector caused an increase of the neomycin phosphotransferase II specific activity. According to the Northern blot hybridization the nptII gene was expressed from the cloned F2 promoter. The apparent transcription start point in E. coli and C. glutamicum was determined. The -35 region of F2 promoter showed high similarity to that of E. coli promoter consensus sequence, but its -10 region was G+C rich and had no significant homology to that. PMID- 7879713 TI - Serological typing of red clover necrotic mosaic virus isolates by enzyme-linked immunosorbent assay. AB - Enzyme-linked immunosorbent assay (ELISA) enabled a more precise serological typing of isolates of red clover necrotic mosaic virus (RCNMV) originating from Slovak and Czech Republics, Poland, Sweden and Great Britain. We found 5 isolates of serotype A, 14 isolates of serotype B, and 6 isolates of serotype C. Some isolates represented mixtures of serotypes, namely A+B (1 isolate), A+C (1), B+C (7), and A+B+C (5). ELISA was found to be a more suitable method of serotype identification of RCNMV isolates than the double diffusion agar gel test for its higher sensitivity and greater selectivity. PMID- 7879714 TI - Purification of rickettsial cultures contaminated by mycoplasmas. AB - An experimental biological model is proposed for purification of rickettsiae infected cell cultures from mycoplasma contamination using intravenous mouse infection and subsequent passages on Vero cell monolayers. Mycoplasma-free rickettsial cultures were obtained in mouse brain or spleen suspension within 3 hrs or 3 days, respectively, after mouse inoculation. Ten strains of spotted fever group rickettsiae were purified from mycoplasmas by this procedure. PMID- 7879715 TI - Persistence of haemagglutination-inhibition antibodies to JE and WN viruses in naturally infected domestic pigs in Karnataka State, India. AB - Domestic pigs were used as sentinels to monitor the prevalence of Japanese encephalitis (JE) and West Nile (WN) viruses in Kolar District of Karnataka State, India. The study revealed that the pigs once seroconverted to JE and WN viruses, remained immune as long as they were available for observation, up to three years. PMID- 7879716 TI - Isolation of Batai virus from sentinel domestic pig from Kolar district in Karnataka State, India. AB - Batai virus was isolated from the blood sample of one sentinel piglet out of 34 used to monitor the activity of the Japanese encephalitis (JE) virus at Madikere village in Kolar district, Karnataka State, India. This is the first report of the isolation of Batai virus from a mammal. PMID- 7879717 TI - Analysis of the 3-deoxy-D-manno-2-octulosonic acid region in a lipopolysaccharide isolated from Coxiella burnetii strain Nine Mile in phase II. AB - Structural analysis of the 3-deoxy-D-manno-2-octulosonic acid (Kdo) region in a lipopolysaccharide (LPS) II isolated from Coxiella burnetii strain Nine Mile in avirulent phase II revealed the presence of three variously linked Kdo residues. The lipid A proximal Kdo is substituted at C-4 by a Kdo-(2-->4)-Kdo disaccharide and this structural arrangement of the Kdo residues is similar to that of enterobacterial LPSs. PMID- 7879718 TI - Isolation of a variant of enterovirus 70 from a patient during an epidemic of acute haemorrhagic conjunctivitis in Pune in 1991. AB - We report on the isolation of enterovirus 70 (EV-70) in Pune, India in 1991. The isolate was identified by the neutralization and indirect immunofluorescent antibody tests. The isolate was found to be a prime type of the EV-70 (J670/71) which was isolated by Kono and collaborators in 1971 (Kono et al., 1974). PMID- 7879719 TI - Thinking globally. PMID- 7879721 TI - In step with Step Beyond. PMID- 7879720 TI - A patient patient. PMID- 7879722 TI - Pseudomemories: the standard of science and the standard of care in trauma treatment. AB - The pseudomemory (PM) debate has focused on individuals who do not remember sexual abuse and later recover these memories, often in therapy. This paper critically reviews experimental research on stress and memory and on suggestibility and memory in terms of its applicability to PM production in therapy. Three different kinds of suggestibility are identified--hypnotizability, postevent misinformation suggestibility, and interrogatory suggestibility. It is hypothesized that interrogatory suggestibility alone or the interaction of all three pose significant risk for PM production. It is argued that a better standard of science is needed before claims can be made about PM production in therapy, since no experimental studies have been conducted on memory performance or suggestibility effects in therapy. However, the findings derived from memory research on other populations, nevertheless, are useful to inform the standard of care in treating recovered memory patients. PMID- 7879723 TI - The validity of repressed memories and the accuracy of their recall through hypnosis: a case study from the courtroom. AB - For 100 years, repressed memories have remained an enigma and a defining point of conflict between various psychological disciplines. Since repressed memories are not readily available for conscious recall, the scientific proof of their existence remains elusive. At the present time, the only way to authenticate the existence of repressed memories is by a case report that documents the reality of the repressed event and then its recall after a period of amnesia. In the following case report, a subject on trial for murder had repressed the events surrounding the crime. Hypnosis was used to recover those memories. That information was then used to dramatically alter the outcome of the trial. PMID- 7879724 TI - Taped therapeutic suggestions and taped music as adjuncts in the care of coronary artery-bypass patients. AB - A randomized, single-blinded, placebo-controlled trial examined the benefits of taped therapeutic suggestions and taped music in coronary-artery-bypass patients. Sixty-six patients listened to either suggestion tapes or music tapes, intraoperatively and postoperatively; 29 patients listened to blank tapes intraoperatively and listened to no tapes postoperatively. Half the patients who listened to a tape found it helpful. There were no significant differences between groups in length of SICU or postoperative hospital stay, narcotic usage, nurse ratings of anxiety and progress, depression, activities of daily living, or cardiac symptoms. There were no significant differences in these same outcomes between the patients who were helped by the tapes and the patients not helped. These results suggest that if taped therapeutic suggestions have a measurable effect upon cardiac surgery patients, demonstrating this effect will require more detailed patient evaluations to identify subgroups of patients responsive to this type of intervention. PMID- 7879725 TI - The effects of light, temperature, trance length, and time of day on hypnotic depth. AB - We evaluated predictions derived from the ultradian theory of hypnosis regarding the effects of temperature, light, trance length, and time of day on reported trance depth in 95 college undergraduates. Temperature and light showed no relation to trance depth. However, as predicted by ultradian theory, subjects who were kept in trance for 15 minutes reported greater trance depth than those who experienced a 5-minute trance. Time of day interacted with subjects' self reported time of peak alertness in the following way: Subjects who reported greatest alertness in the morning achieved greater trance depth in the morning than in the evening, whereas those subjects who reported greater evening alertness reported deeper trance in the evening than in the morning. This latter finding was inconsistent with ultradian theory and prior research. Alternative explanations for this finding are discussed. Overall, the results from the present study do not provide strong support for Rossi's ultradian theory of hypnosis. PMID- 7879726 TI - Biofeedback-aided hypnotherapy for intractable phobic anxiety. AB - Phobically avoidant people need treatments that enable them to cope effectively with their task threats. Field-mastery techniques that emphasize the importance of cognitively and behaviorally active roles to be taken by both therapist and patient have been shown to be superior to the clinic-based exposure and encouragement approaches. This paper describes a treatment model used with patients who were refractory to any performance-based treatment because of various reasons, primarily intense fear of even the initial guided exposure. Biofeedback-aided hypnotherapy (BAH) was the integrated new treatment employed. It offered the simultaneous safety of the clinic, enhanced vivification of the feared situation, combined with continuous convincing feedback about the growing mastery. BAH may ease the fear associated with the binary leap from in-vitro treatment to actual exposure. This treatment offers an alternative to phobic patients who are too fearful to engage in any other effective treatment modality. PMID- 7879727 TI - Requirements and toxicity of essential trace elements, illustrated by zinc and copper. AB - Early signs of toxicity of essential trace elements are important. Some trace elements are available over-the-counter (OTC) and/or are present at industrial waste sites. Physicochemically similar trace elements compete for ligands, impairing functions, which is exemplified by the zinc-copper antagonism described long ago by Van Campen, Hill and Matrone, and Klevay. Intestinal absorption of copper is inhibited by zinc. Thus risk of copper deficiency is increased when the molar ratio of zinc to copper (Zn:Cu) is high. As shown by experiments, copper deficiency can occur in humans. Manifestations include decreased erythrocyte copper-zinc superoxide dismutase, increased low-density-lipoprotein cholesterol, decreased high-density-lipoprotein cholesterol, decreased glucose clearance, decreased methionine and leucine enkephalins, and abnormal cardiac function. Calculation of a preliminary reference dose for OTC zinc that assumed high bioavailability and uncertain copper intakes established 9 mg as a safe amount for 60-kg adults. PMID- 7879728 TI - Nutrition and environmental health. Proceedings of a symposium. Anaheim, California, April 25-26, 1994. PMID- 7879729 TI - Asthma, inhaled oxidants, and dietary antioxidants. AB - The possible influence of dietary antioxidants, especially vitamin C, on the increasing prevalence of asthma is explored. Vitamin C intake in the general population appears to correlate with asthma, suggesting that a diet low in vitamin C is a risk factor for asthma. Epidemiological studies show associations among oxidant exposure, respiratory infections, and asthma in children of smokers. Symptoms of ongoing asthma in adults appear to be increased by exposure to environmental oxidants and decreased by vitamin C supplementation. There is evidence that oxidants produced endogenously by overactive inflammatory cells contribute to ongoing asthma. Vitamin C is the major antioxidant substance present in the airway surface liquid of the lung, where it could be important in protecting against both endogenous and exogenous oxidants. Nitrogen oxides are exemplary of oxidants that could arise from both endogenous and environmental sources, which are protected against by vitamin C, and that may be important in causation and propagation of asthma. PMID- 7879730 TI - Environmental and physical stress and nutrient requirements. AB - When faced with hot, cold, or high-altitude environments, humans can either modify the microenvironment to fit human physiology, adapt their physiology to fit the environment, or use a combination of these two tactics. Metabolic adaptations to heat, cold, and high-altitude exposure may, in some instances, be accompanied by changes in nutrient requirements. Energy expenditure is increased in all three environments. B-vitamin cofactor requirements increase in proportion to energy expenditure (oxidation of fat and carbohydrate). Increased B-vitamin nutrient requirements are usually adequately met by an increased consumption of the diet to meet energy requirements. Other nutrients such as iron may be required in greater amounts to meet the altitude-induced hematopoietic response in females. Additional quantities of vitamins and minerals with antioxidant properties may be beneficial to reduce the increased oxidative stress associated with work in heat, cold, or high-altitude outdoor environments. PMID- 7879731 TI - Environmental factors that influence the cutaneous production of vitamin D. AB - All vertebrates, including humans, obtain most of their daily vitamin D requirement from casual exposure to sunlight. During exposure to sunlight, the solar ultraviolet B photons (290-315 nm) penetrate into the skin where they cause the photolysis of 7-dehydrocholesterol to precholecalciferol. Once formed, precholecalciferol undergoes a thermally induced rearrangement of its double bonds to form cholecalciferol. An increase in skin pigmentation, aging, and the topical application of a sunscreen diminishes the cutaneous production of cholecalciferol. Latitude, season, and time of day as well as ozone pollution in the atmosphere influence the number of solar ultraviolet B photons that reach the earth's surface, and thereby, alter the cutaneous production of cholecalciferol. In Boston, exposure to sunlight during the months of November through February will not produce any significant amounts of cholecalciferol in the skin. Because windowpane glass absorbs ultraviolet B radiation, exposure of sunlight through glass windows will not result in any production of cholecalciferol. It is now recognized that vitamin D insufficiency and vitamin D deficiency are common in elderly people, especially in those who are infirm and not exposed to sunlight or who live at latitudes that do not provide them with sunlight-mediated cholecalciferol during the winter months. Vitamin D insufficiency and deficiency exacerbate osteoporosis, cause osteomalacia, and increase the risk of skeletal fractures. Vitamin D insufficiency and deficiency can be prevented by encouraging responsible exposure to sunlight and/or consumption of a multivitamin tablet that contains 10 micrograms (400 IU) vitamin D. PMID- 7879732 TI - Nutrition and metal toxicity. AB - Lead, cadmium, and mercury are toxic metals that are not essential for nutrition. However, the toxic effects of these metals may be mediated or enhanced by interactions or deficiencies of nutritionally essential metals. Lead competes with calcium, inhibiting the release of neurotransmitters, and interferes with the regulation of cell metabolism by binding to second-messenger calcium receptors, blocking calcium transport by calcium channels and calcium-sodium ATP pumps, and by competing for calcium-binding protein sites and uptake by mitochondria. Dietary deficiencies of calcium, iron, and zinc enhance the effects of lead on cognitive and behavioral development. Iron deficiency increases the gastrointestinal absorption of cadmium, and cadmium competes with zinc for binding sites on metallothionein, which is important in the storage and transport of zinc during development. Selenium protects from mercury and methyl mercury toxicity by preventing damage from free radicals or by forming inactive selenium mercury complexes. PMID- 7879733 TI - Influence of nutrients and other dietary materials on cytochrome P-450 enzymes. AB - The cytochrome P-450 (P-450) enzymes are collectively responsible for the bulk of oxidation of xenobiotic chemicals, including drugs, pesticides, and carcinogens. This biotransformation can result in either increased or decreased toxicity, depending on the situation. The regulation of individual P-450 enzymes is a complex subject, with examples of induction and direct inhibition and stimulation. Nutrients and food additives can modify P-450 activities and consequently influence toxicity. P-450s also influence the toxicity of potentially harmful materials found in foods, as well as some vitamins and natural products. Some of the foodstuffs and conditions that influence P-450 in experimental animals and in humans are protein, carbohydrate, lipid, obesity and fasting, water- and fat-soluble vitamins, minerals, sulfides, isothiocyanates, indoles, ellagic acid, capsaicin, terpenes, flavones, butylated hydroxytoluene and hydroxyanisole, charbroiled foods, ethanol, and (monosodium) glutamate and aspartate. Consideration is given, when possible, to differences in responses between animal models and humans. PMID- 7879734 TI - Methyl donors in the diet and responses to chemical carcinogens. AB - Dietary deficiency of labile methyl donors (choline and methionine) increases spontaneous and chemically induced hepatocarcinogenesis in rats. Chemical carcinogenesis in the colon, mammary gland, esophagus, and pancreas also may be increased. The mechanism of the dietary effect is not known but may be related to reduced methylation of DNA and RNA, hyperplasia of target cells, increased peroxidative damage, and altered carcinogen or promoter metabolism. Folate deficiency also is associated with increased carcinogenesis, an effect that may be mediated through participation in methyl metabolism; this has been less extensively studied. Deficiency of these three nutrients also may play a role in the elevated cancer risk in humans that is associated with ethanol intake. PMID- 7879735 TI - Model for the epigenetic mechanism of action of nongenotoxic carcinogens. AB - On the basis of studies with carcinogenic nickel compounds, we propose a new model of how epigenetic carcinogens might act. This model is based on the fact that nickel compounds induce an increase in chromatin condensation, causing neighboring genes that are actively expressed in euchromatin to be condensed into heterochromatin. Such redistribution in condensation of chromatin would probably only be transient were it not for the DNA cytosine methyl transferase enzyme, which through de novo methylation can cause genes to be inherited in an active state. Actively expressed genes have less cytosine methylation in their promoter whereas hypermethylation of cytosine in promoters is characteristic of inactive genes. Therefore, nickel, through induction of an enhanced condensation state of chromatin that results in the incorporation of critical genes such as the senescence and tumor suppressor genes into heterochromatin (ie, thread on a spool) and the subsequent methylation of this DNA, silences the genetic activity that might be essential for maintenance of a normal cell. This model is consistent with the literature on cytosine methylation and is also consistent with studies of nickel carcinogenesis showing that it increases cytosine methylation. It is also consistent with nickel carcinogenesis being synergistic with many other mutagenic carcinogens (ie, x rays, benzopyrene, or ultraviolet light), which has always suggested that it has a unique component that is not part of the mechanism of these mutagenic carcinogens. PMID- 7879736 TI - Oxidation of low-density lipoproteins: questions of initiation, propagation, and the effect of antioxidants. AB - Oxidation of low-density lipoproteins (LDLs) plays a role in the development of atherosclerosis, but many questions remain unanswered. This paper aims to evaluate critically the available data pertinent to the following questions: 1) How is LDL oxidation initiated, especially in early atherosclerotic lesions? 2) Is nitric oxide good or bad in lesions? and 3) Which antioxidants are really important in protecting LDLs against oxidation in the human body? PMID- 7879737 TI - Perspectives on the interrelations between nutrition and the environment. PMID- 7879738 TI - Environmental contaminants in the food chain. AB - Both terrestrial and aquatic food chains are capable of accumulating certain environmental contaminants to toxic concentrations. This article focuses on the aquatic food chain because we have less control over contaminant entry into this chain than we have for the terrestrial chain. In general, at least three special properties are required for a contaminant to bioaccumulate in an aquatic food chain: 1) a high octanol-water partition coefficient, 2) chemical and metabolic stability in water and in organisms in the food chain, and 3) a low toxicity to organisms in the chain so that the chain is not broken by loss of an intermediate species. Few of the thousands of chemicals produced by human industry meet these requirements. In terms of organic chemicals, the best known examples of bioaccumulation in aquatic food chains are the polychlorinated biphenyls (PCBs), dioxins, and organochlorine pesticides such as dichlorodiphenyltrichloroethane (DDT). Few examples exist of bioaccumulation of metal compounds. Methylmercury is arguably the most dramatic and best documented example of high bioaccumulation. PMID- 7879739 TI - Effects of xenobiotics on milk secretion and composition. AB - Xenobiotics have the potential of disrupting the differentiated function of the mammary gland, that is, milk secretion, by inhibiting mammary development, by directly interfering with the secretory function of the mammary alveolar cell, by altering the hormonal milieu that supports lactation, or by impeding nutrient transport to the mammary cell. Although solid information is lacking in most of these areas, available research suggests that antiestrogens may interfere with mammary development, that oxidants and phorbol esters may inhibit milk secretion, that ergot alkaloids and alcohol may alter the hormonal milieu, and that dioxins may interfere with lipid transport to the mammary gland. Models for the investigation of these and other environmental toxins and drugs are suggested. PMID- 7879740 TI - Mechanism of action of dioxin-type chemicals, pesticides, and other xenobiotics affecting nutritional indexes. AB - The most consistent toxic effects of dioxin-type chemicals are hyperlipidemia, body weight loss (particularly body fat loss), anorexia, changes in carbohydrate metabolism, and lipid peroxidation. The biochemical systems particularly affected are lipoprotein lipases, low-density-lipoprotein receptors, glucose transporter proteins (GLUTs), vitamin C uptake, and insulin secretion. Some of these biochemical changes occur at very low doses, and some effects can last for long time periods. To provide a mechanistic explanation for such actions of dioxins, available experimental evidence has been reviewed. The most recent discovery indicates that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) directly acts with isolated cytosolic aryl-hydrocarbon (Ah) receptor under cell-free conditions even without the presence of the nucleus and is capable of activating key protein kinases that are involved in the growth factor signal-transduction pathway. The resulting activation of primary-response transcription factors in the nucleus appears to play a key role in coordinating vital cell program shifts, including lipid metabolism. PMID- 7879741 TI - Future of dietary exposure assessment. AB - Nutritional epidemiology depends on valid assessment of exposure of individuals to food-borne factors. The tools being applied are generally blunt instruments that are simple for the scientist to administer and analyze. The burden of aggregating foods, combining amounts, drawing on episodic or generic memory, and interpreting the questions is placed on the subjects. Alternative approaches include enhanced use of biomarkers of exposure as external, internal, and target tissue markers. Because biomarkers exist for only a few substances of interest at the exposure time of interest, the future of subjective measures is likely to be in the development of subjective dietary assessment methods that apply modern technology, including audio systems to overcome literacy barriers and allow multilingual interviews, and pictures for identifying foods. Automated methods can ensure that all questions have been responded to and all responses outside of normal ranges have been double-checked. Computer-assisted self-interviewing (CASI) may prove to be the most economic and cognitively supportive approach for assessment of food-borne exposures in the future. PMID- 7879742 TI - Biomarkers for assessing environmental exposure to carcinogens in the diet. AB - The major sources of human exposure to environmental carcinogens are through inhalation, ingestion, and percutaneous absorption. Food-borne carcinogens constitute the primary source of ingested carcinogens. Epidemiological analyses indicate that 20-50% of all human cancer is due to dietary causes, unfortunately, few specific etiologic agents have been identified. The use of chemical-specific molecular biomarkers in studies of several classes of carcinogens to which humans are exposed through the ingestion of food may provide the necessary data to identify these etiologic agents. These molecular biological markers can be classified into several categories: markers of exposure reflecting dose of toxic agents, markers of effect indicating a biological response to an exposure, and markers of susceptibility providing information about the inherent sensitivity of an individual to the toxic agent. By definition some of these markers are chemical-agent specific, such as a carcinogen-DNA or carcinogen-protein adduct, whereas others are biological process-specific such as the altered expression of a gene. In the future, information obtained from studies of molecular biomarkers in humans and experimental animals can be used for a range of public health applications from primary and secondary prevention to the design of clinical therapies. Aflatoxins have been extensively studied with validated biomarkers, and, currently, dietary polycyclic aromatic hydrocarbons (PAH) and heterocyclic amines (HA) derived from cooking meats and other staples are being intensively investigated. This article reviews some of the recent information on aflatoxins and describes future potential of PAH and HA biomarkers. PMID- 7879743 TI - Long-term fat intake and biomarkers. AB - The patterns of fatty acids maintained in human tissues reflect the dietary abundances of n-3 and n-6 fatty acids and the selectivities of the various lipid metabolizing enzymes and transport systems in tissues. Similar selectivities for enzymes of mice, rats, and humans permit data from all three to be used in predicting average long-term tissue responses to different diets. The participation of the highly unsaturated fatty acids arachidonate (an n-6 acid) and eicosapentaenoate (an n-3 acid) in chronic pathophysiological events gives importance to predicting their tissue abundance. The average proportions in tissue phospholipids are hyperbolically related to dietary supplies of their precursors linoleate (18:2n-6) and linolenate (18:3n-3). In contrast, the precursors are maintained in tissue triacylglycerols in a linear relation to their average dietary supply. PMID- 7879744 TI - Lipoproteins, nutrition, aging, and atherosclerosis. AB - Coronary heart disease (CHD) risk increases markedly with age in both men and women. Major risk factors for CHD in addition to diet and lifestyle factors include age, family history of CHD, cigarette smoking, hypertension, diabetes, elevated low-density-lipoprotein (LDL) cholesterol (> or = 4.1 mmol/L, or 160 mg/dL), and decreased high-density-lipoprotein (HDL) cholesterol (< 0.09 mmol/L, or 35 mg/dL). A diet containing < or = 30% of energy from fat, < 10% from saturated fat, and < 300 mg cholesterol/d for the general population for CHD risk reduction, and a further restriction of < 7% of energy from saturated fat and < 200 mg cholesterol/d for hypercholesterolemic subjects has been recommended. Such diets have been shown to reduce CHD risk. Age-adjusted CHD mortality rates have declined by 50% over the past four decades, probably because of decreases in animal fats in the diet, better control of hypertension, and efforts at smoking cessation. PMID- 7879745 TI - The multidimensional nature of received social support in gay men at risk of HIV infection and AIDS. AB - This article concerns received social support in gay men at risk of HIV and AIDS. Distinctions are made between three types of support (informational, tangible, emotional), four sources of support (friends, relatives, partner, organizations), and three dimensions of support (amount, satisfaction, reciprocity). A 24-item inventory reflecting these distinctions was administered to a sample of 587 gay men at two points in time. The psychometric properties of the instrument were determined, and the factor structure of the items varying sources and types of social support were tested. This was done by exploratory as well as by confirmatory factor analyses. The hypothesized structure was confirmed in both waves separately. Results corroborated the assumption that enacted or received social support is a highly differentiated construct and requires assessment tools that are designed according. Descriptive results on the support perceptions in this sample are also presented. Implications for the study of support in men at risk of HIV and AIDS are discussed. PMID- 7879746 TI - A longitudinal study of school adjustment in urban, minority adolescents: effects of a high school transition program. AB - Described an intervention program designed to prepare elementary school (K-8) eighth-grade students for their transition to high school the following year. Participants in the study were 145, predominantly Hispanic, inner-city public school adolescents. The experimental group received an augmented condition, consisting of Education and Peer Support Components. The control group received a minimal condition consisting of only the Education Component. While no group effects were observed, time effects indicated experimental and control students' improved perceptions of school readiness, but deteriorated perceptions of support from both home and school and diminished grade-point averages and attendance. Time effects also revealed variable changes in school perceptions. Findings are discussed in terms of a developmental perspective of the school transition process. Implications for high school transition programming with the target population and directions for future research are also addressed. PMID- 7879747 TI - Socioenvironmental experiences, self-esteem, and emotional/behavioral problems in early adolescence. AB - Tested the role of self-esteem as a mediator of relationships between socio environmental experiences and emotional/behavioral problems using a sample of 215 young adolescents (Grades 7-9). Socioenvironmental experiences were assessed using self-report questionnaire measures of social support and major and minor stressful events. Self-esteem was assessed using a self-report questionnaire, an interview, and a parent-report questionnaire. Emotional/behavioral problems were assessed using self-report, parent-report and teacher-report questionnaires. Utilizing structural equation modeling, the data were used to test a model in which self-esteem mediated the relationship between socioenvironmental experiences and emotional/behavioral problems. The hypothesized model provided a reasonably good fit to the data (normed fit index = .90). However, an alternative model which also allowed for direct effects of socioenvironmental experiences on emotional/behavioral problems produced a significant improvement in model fit. In this model, socio-environmental experiences had significant effects on emotional problems via both direct effects and indirect effects that indicated a mediating role for self-esteem. Only direct effects of socioenvironmental experiences were evident for behavioral problems. PMID- 7879748 TI - Social problem solving in unsafe situations: implications for sexual abuse education programs. AB - Examined the impact of two subject variables (age and gender) and two contextual factors (antagonist age and nature of the social dilemma) on children's social problem solving (SPS). Preschoolers (N = 62) were individually presented with four stories that varied the antagonist age (peer vs. adult) and social dilemma (nonsexual vs. sexual). Responses were coded for three SPS variables: number of alternative solutions, solution content, and planfulness. Younger preschoolers were less competent problem solvers in all types of unsafe situations, and, compared to girls, some aspects of boys' problem solving were compromised in sexual encounters. Results also suggest that the nature of the social dilemma, but not the age of the antagonist, affects preschoolers' SPS. Children generated fewer alternative solutions and fewer effective strategies to the sexual encounters compared to the nonsexual dilemmas. Findings are discussed in relation to research on children's SPS and child sexual abuse prevention efforts. PMID- 7879749 TI - My place, your place, and no place: behavior settings as a risk factor for HIV related injection practices of drug users in Baltimore, Maryland. AB - Information is sparse on the social context of illicit drug injection behaviors and their relationship to HIV infection. This study examined relationships between injection settings, injecting with others, and HIV risk behaviors of sharing needles and not cleaning contaminated needles in a sample of 630 inner city injecting drug users in Baltimore, MD. Through open-ended interviews, five primary settings of injection behavior were identified. These settings included one's own, friends' and mother's residence, shooting galleries, and semipublic areas. Most participants reported injecting in their own residence (92%) and friends' residence (86%) in the prior 6 months. In a multiple regression analysis, injecting at friends' residence, in shooting galleries, and in semipublic areas and frequency of injecting with others were significantly associated with frequency of sharing uncleaned needles, "slipping" (i.e., failure to disinfect shared needles), and not always cleaning used needles before injecting. Results suggest that interventions may benefit from targeting settings as well as behaviors to reduce the spread of HIV. PMID- 7879750 TI - Comment on TMD. PMID- 7879751 TI - Government and orthodontics in California in 1994. PMID- 7879752 TI - The effectiveness of an extreme canine-protected splint with limited lateral movement in treatment of temporomandibular dysfunction. AB - This study suggests that a splint design incorporating extreme canine guidance with limited lateral movement may be effective in the treatment of temporomandibular dysfunction (TMD) symptoms. Fifty consecutively treated TMD patients were evaluated with the TMJ Scale before and after treatment. A group of 11 similar patients identified as having TMD, but who declined treatment, were used as a control group. PMID- 7879753 TI - Small is beautiful. PMID- 7879754 TI - Uprighting impacted second molars with segmented springs. AB - Severe impaction of lower second molars often leads to their extraction to avoid potential damage to the first molar root. We present a case in which we used the clinical application of simple biomechanical principles to allow us to upright bilaterally impacted lower second molars into the desired location in a fairly short time. PMID- 7879755 TI - Mixed dentition case report. AB - Malocclusions can be successfully corrected by phase I mixed dentition therapy and significantly reduce the need for comprehensive orthodontic treatment in the permanent dentition. Phase I orthodontic treatment is designed to correct the skeletal and dental malocclusions at an early age with 12 to 18 months of treatment. After phase I treatment, there is a supervision phase of typically 18 to 30 months to hold the correction achieved and to supervise the eruption of the remaining permanent teeth. Good management during the supervision phase is key to maintaining the phase I result and to minimizing phase II treatment. If a second phase of orthodontic treatment is required, treatment time is usually limited to 6 to 18 months, depending on the malocclusion and growth pattern. In this case, full banded treatment and maxillary intrusion surgery was not recommended because of the excellent early treatment result. Reduction of vertical anterior maxillary excess can be successfully achieved with early mixed dentition treatment and remain stable during the supervision phase of treatment. At the University of the Pacific, mixed dentition treatment is an integral part of the graduate program in orthodontics. This patient had a severe skeletal ANB angle discrepancy of 8 degrees, a vertical growth pattern, and 8 mm of overjet. She was considered an excellent candidate for phase I treatment to reduce the severity of the problem. It is our philosophy to take advantage of the growth potential in a patient by initiating phase I treatment between the ages of 7 and 9 years, depending on the eruption of the permanent first molars and incisors and the severity of the malocclusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879756 TI - The use of implants for orthodontic correction of an open bite. AB - This case illustrates the integration of maxillofacial surgery, orthodontics, prosthodontics and periodontics in the treatment of an adult male. A traumatic injury to the lower jaw was the stimulus for the patient to seek orthodontic correction of a severe malocclusion including crossbites and an anterior open bite. The loss of a large portion of the anterior alveolar process of the lower jaw including six teeth was corrected with an implant bearing prosthesis which was subsequently used as anchorage to correct the malocclusion. Through the combined efforts of the above disciplines, properly orchestrated, this patient was treated in an effective and successful manner. PMID- 7879757 TI - A new device for absolute anchorage for orthodontics. AB - A new device has been designed to provide anchorage for orthodontic tooth movement. It is a disk, textured and hydroxylapatite coated on one side, with an internal thread on the other side. It is placed on palatal bone and, after integration, can be connected to teeth for anchorage. This article reviews a dog study demonstrating unilateral tooth movement towards the "onplant" and a monkey study mimicking its use to anchor the molars for anterior retraction. PMID- 7879758 TI - Identification of nasal morphologic features that indicate susceptibility to nasal tip deflection with the LeFort I osteotomy. AB - The goal of this investigation was to identify and quantify nasal morphologic features which predispose to the nasal tip deflection associated with the LeFort I osteotomy. Fifty patients who had undergone LeFort I osteotomies were studied retrospectively from presurgical and postsurgical cephalograms and facial photographs. The magnitude of hard tissue change was measured in the vertical and horizontal planes, and soft tissue nasal change was measured in the vertical plane at two points on the outline of the soft tissue nose. Additional parameters were tested as potential predictors of nasal tip deflection, including the Deflection Resistance Index (DRI), which is a quantitative measure of nasal morphologic features. Data were subjected to a hierarchical multiple regression analysis allowing for multivariate prediction capability. At the supra nasal tip (SNt), magnitude of advancement, magnitude of impaction, and the DRI were all significant predictors (multiple R = 0.86). At the anterior nasal tip (ANt), magnitude of advancement, preoperative columellar angle, magnitude of impaction, the DRI, the interactions of advancement and DRI, and columellar angle and DRI were the significant predictors (multiple R = 0.89). It is concluded that the vertical deflection of the nasal tip resulting from the LeFort I osteotomy is influenced not only by the hard tissue movements but also by nasal structure. The DRI is a quantitative measure that can be used clinically to improve the predictability of vertical nasal tip deflection. PMID- 7879759 TI - Rapid maxillary expansion in the deciduous and mixed dentition evaluated through posteroanterior cephalometric analysis. AB - There is an agreement among orthodontists that a posterior crossbite relationship should be treated early. The Haas expansion appliance is frequently chosen whenever a maxillary skeletal constriction exists in the deciduous, mixed, or permanent dentition. In this study we evaluated the efficacy of rapid maxillary expansion for 32 children between 5 and 11 years of age, by inspection of anteroposterior radiographs. Our results confirm previous data in the literature that the triangular opening in the frontal alveolar area is greater than in other parts of the midpalatal suture. It is evident that with expansion there is a real orthodontic effect, even at an early age. PMID- 7879760 TI - Long-term stability of Angle Class II, division 1 malocclusions with successful occlusal results at end of active treatment. AB - The purpose of this study was to examine long-term stability of Angle Class II, Division 1 malocclusions with successful occlusal results at the end of active appliance therapy, search for predictors of relapse, and look for characteristics associated with successful treatment. Records taken before and after treatment and a mean of 14.0 years postretention of adolescent patients treated for a significant Angle Class II, Division 1 malocclusion both with and without tooth extraction were evaluated. The sample was limited to successfully treated cases as judged by subjective evaluation of intercuspation and incisor occlusion of posttreatment study models and included 78 patients. Cephalometric characteristics or postretention occlusion was not considered in sample selection. The mode response was no change postretention for molar, premolar, and canine relationships and relapse of 0.5 mm for overjet and overbite. Maximum relapse was 3.5 mm for molar, premolar, and canine relationship, 3 mm for overjet, and 4.5 mm for overbite. Stepwise backward multiple regression analyses revealed no associations between either pretreatment characteristics or skeletal and dental treatment changes and relapse of overjet. However, relapse of overjet was associated with relapse of molar, premolar, and canine relationships, postretention increase in overbite, postretention proclination of maxillary incisors, and postretention retroclination of mandibular incisors. Active treatment changes included redirection or inhibition of maxillary growth and retraction of maxillary incisors. Mandibular incremental growth was favorable both during and after treatment. It was concluded that successful correction of Angle Class II, Division 1 malocclusions through differential growth adaptation and tooth movement appears to be very stable. PMID- 7879761 TI - Craniofacial morphology, occlusal traits, and bite force in persons with advanced occlusal tooth wear. AB - The aim of this study was to investigate the dentofacial structure, the occlusal traits, and the bite force in subjects with advanced occlusal wear. The material comprised 54 adults, 30 men (mean = 40 years, range 16 to 61) and 24 women (mean = 28 years, range 18 to 47), most of whom had a full or near-full complement of natural teeth, and the presence of occlusal wear. Craniofacial structure was studied on lateral cephalograms. Occlusal traits were examined on study casts, these serving also for an evaluation of occlusal wear to be carried out by using an ordinal scale. Bite forces were recorded at differing force levels (maximum biting, "biting as when chewing" and "light biting") and occlusal positions. Although maximum bite force and endurance time did not differ significantly between men and women, the level of bite force was high compared with other samples. The craniofacial structure of the sample was characterized by a deviation in the vertical direction, a small angle between the mandibular-palatal planes and a small gonial angle, as compared with Swedish adult norms. No significant differences were found in anteroposterior relationships between persons with advanced wear and normal standards. The results support the hypothesis that functional hyperactivity of the masticatory system imposed increased stress on the bony structures of the craniofacial complex with possible influences on its structure. PMID- 7879762 TI - Clinical effectiveness of fluoride-releasing elastomers. I: Salivary Streptococcus mutans numbers. AB - The purpose of this study was to examine the effect of fluoride-releasing elastomers on salivary Streptococcus mutans numbers. Twenty-four patients with fixed orthodontic appliances were randomly divided into experimental and control groups consisting of 12 patients each. Conventional elastomers were in place while two baseline whole saliva samples were collected from each subject in both groups at their regular appointments. After the second baseline sample was taken, conventional elastomers were replaced with fluoride-releasing elastomers in the experimental group, whereas conventional elastomers were continued in the control group. Three saliva samples were then collected from all subjects at 1-week intervals. Conventional elastomers were placed in all subjects while two postexperimental saliva samples were collected at regular appointments. Results showed that the control group demonstrated no significant changes (p > 0.05) in the percentage of S. mutans over the 13-week study period. However, after the fluoride-releasing elastomers were placed, the percent of salivary S. mutans decreased significantly (p < 0.01) in the experimental group. There was no significant effect after the fluoride-releasing elastomers were in place for 2 or more weeks. PMID- 7879763 TI - A three-dimensional comparison of condylar position changes between centric relation and centric occlusion using the mandibular position indicator. AB - The mandibular position indicator (MPI) was used to compare condylar position between centric relation (CR) and centric occlusion (CO) for 107 patients before orthodontic treatment. The MPI data were examined to determine frequency, direction, and magnitude of CO-CR difference; and data were analyzed for possible correlation to the patient's Angle classification, ANB angular measurement, age, or gender. Only one patient (0.9%) had no measurable CO-CR difference in all three spatial planes. Six subjects (5.6%) showed a shift in condylar position in the transverse plane without a measurable difference in the sagittal plane. Twenty patients (18.7%) experienced a superoinferior (SI) or anteroposterior (AP) condylar displacement of at least 2.0 mm on one or both sides; 17 (15.9%) displayed a transverse shift at the level of the condyles of 0.5 mm or greater. No statistical difference was found between the 31 patients with Class I malocclusions and 72 patients with Class II malocclusions when comparing the amount or direction of CO-CR change. The amount of CO-CR difference was nearly identical for right and left sides with the amount of SI displacement (x = 0.84 mm) consistently greater than AP displacement (x = 0.61 mm). Only weak correlations were found between movements of right and left condyles. The average transverse CO-CR difference was 0.27 mm. Patient age, ANB angle, gender, or Angle classification cannot be used to predict frequency, magnitude, or direction of CO CR changes at the level of the condyles. PMID- 7879764 TI - Prediction of mesiodistal diameter of unerupted lower canines and premolars using 45 degrees cephalometric radiography. AB - The reliability of using the oblique cephalometric radiograph for early prediction of the mesiodistal widths of unerupted lower canines and premolars was investigated. Mandibular models and oblique cephalometric radiographs were obtained for 40 Brazilian children (20 boys and 20 girls), in the mixed dentition phase. Further models were obtained for the same sample when all permanent teeth had erupted. A Student t test showed statistically significant differences of tooth size between the sexes but not between right and left sides. Measurements of the unerupted canines and premolars taken from the 45 degrees cephalometric radiograph were statistically greater than the actual values, although a high correlation was observed between them. Linear regression equations and correction tables were established to compensate for this magnification. The actual values for these teeth were compared with the corrected predicted values from the 45 degrees radiograph and with the predicted values obtained from the methods of Ballard and Wylie, Carey, Moyers, and Tanaka and Johnston. A high correlation was observed only between the actual values and the corrected predicted values from the radiograph. The results indicate that, correcting the magnification, the 45 degrees cephalometric radiographic may be used in predicting unerupted lower canine and premolar widths in Brazilian children. PMID- 7879765 TI - Occlusion and condylar position. PMID- 7879766 TI - A three-dimensional comparison of condylar change between centric relation and centric occlusion using the mandibular position indicator. PMID- 7879767 TI - The effectiveness of Class II, division 1 treatment. AB - The aim of this retrospective study was to evaluate the effectiveness of orthodontic treatment in terms of two outcome variables, namely, the percentage change in a valid and reliable occlusal index, the Peer Assessment Rating (PAR) score, and the duration of treatment. Data were collected from the records of 250 patients with Class II, Division 1 malocclusions who were treated in the Orthodontic Department of the University of Pittsburgh between 1977 and 1989. The relationships between the outcome and the treatment variables were analyzed with multiple regression techniques. Those variables significantly associated with the duration of treatment (p < 0.01) were (1) the pretreatment PAR score, (2) the number of treatment stages, (3) the percentage of appointments attended, (4) the number of appliance repairs, and (5) whether the patient was treated with or without extractions. The only variable that influenced the percentage change in PAR was the pretreatment PAR score (p < 0.01). PMID- 7879768 TI - An introduction to the Internet. PMID- 7879769 TI - DNA typing in forensic science. I. Theory and background. AB - In the last few years, DNA typing procedures have become increasingly important in the fields of forensic science and forensic medicine. This paper reviews background information on DNA and human genetics, and addresses how molecular techniques such as restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) analysis have been used to detect genetic polymorphism in human populations. The systems discussed include single locus RFLP, HLA DQ-alpha, amplified fragment length polymorphism (AMP-FLPs), short tandem repeats (STRs), and mitochondrial DNA typing. Several DNA typing methods have been thoroughly validated for forensic use. With proper control measures, DNA analysis should be considered reliable. At this time, DNA evidence/testimony is generally accepted by the courts and greatly assists in the resolution of criminal and civil investigations. PMID- 7879770 TI - Destructive hostility: the Jeffrey Dahmer case. A psychiatric and forensic study of a serial killer. AB - We were involved as forensic experts in the case of the serial killer Jeffrey Dahmer. We discuss the scene and victim autopsy findings, with a brief consideration of the basic emotion of hostility. These findings support the thesis that at the basis of this serial killer's behavior were primary unconscious feelings of hate that he had channeled into a sadistic programmed destruction of 17 young men. The interview of the serial killer, the photographic scene documentation, and the autopsy findings stress the ambivalent homosexuality of the killer, his sexual sadism, his obsessive fetishism, and his possible cannibalism and necrophilia. PMID- 7879771 TI - The investigation of fatal falls and jumps from heights in Maryland (1987-1992). AB - This study is a retrospective analysis of 139 cases of falls and/or jumps from heights, examined at the Office of the Chief Medical Examiner for the State of Maryland during the 6-year period from 1987 through 1992. A total of 56 individuals (40%) committed suicide by jumping from heights and 72 (52%) fell accidentally. Of the 72 accidental falls, 36 (50%) were work related. Two cases involved victims of homicide and the causes in nine cases remain undetermined. Of the 139 cases examined, 89 individuals (64%) fell or jumped from buildings, 29 (21%) from bridges, 15 (11%) from ladders, and 6 (4%) from trees or electric poles. Of the 29 individuals who fell or jumped from bridges, 14 went into water. Falls and jumps most often involved whites (78%) and males (82%). Their ages ranged from 4 to 83 years, with the majority in their 20s and 30s. Of the 124 people who fell or jumped from heights and landed on the ground, the head was the most frequently injured body region (70%), followed by the chest (66%), the abdomen (48%), extremities (28%), and the neck (19%). Of the 124 victims who landed on the ground, 63 sustained lethal injuries involving multiple organs. In contrast with ground impacts, water impact injuries were much less severe. Five of the 14 victims who jumped from bridges into water were relatively uninjured and died from drowning even though they jumped from heights of 100-200 feet (30 60 m).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879772 TI - Flow cytometric evaluation of DNA degradation: a predictor of postmortem interval? AB - The time of death of an individual can easily be determined if the postmortem interval can be assessed. Although livor mortis, rigor mortis, and, to a lesser degree, algor mortis have been used to estimate the postmortem interval, most experienced forensic pathologists agree that these characteristics provide, at best, "postmortem windows." Quantitation of the vitreous fluid potassium level has been of some value in evaluating the early postmortem interval, but the accuracy of this method is dependent on external conditions, the availability of vitreous fluid (e.g., burned bodies, head trauma), and the purity of the sample. A simple, relatively inexpensive assay performed on readily available tissues, less dependent upon external factors, and providing data that could be plotted on a reproducible control curve would be of value in determining the postmortem interval accurately. This office is currently investigating flow cytometric DNA content analysis performed on splenic tissue harvested from a series of autopsies with known postmortem intervals. Preliminary data suggest that DNA degradation occurs in a predictable pattern over the intermediate postmortem period. A graph is being generated that will plot the degree of DNA fragmentation with respect to the postmortem interval. It is hoped that sections of spleen from "unknown" cases could be submitted for flow cytometric analysis of DNA content and plotted on the curve to estimate the postmortem interval and, thus, determine the time of death. PMID- 7879773 TI - Age estimation using dental periapical radiographic parameters. A review and comparative study of clinically based and regression models with the Operation Desert Storm victims. AB - A brief discussion of teeth and aging is followed by a review of the first four studies by our group at Temple University. In the present study, periapical, postmortem radiographs taken with the bisecting-angle technique from U.S. armed forces personnel killed during Operation Desert Storm were analyzed for age estimation. A total of 74 sets of dental radiographs (52 complete and 22 incomplete) with documented age of the individual at the time of death recorded were examined by investigators (D.R.M. and J.V.E.), who were blind to age range and specific ages of the victims. Comparisons were made between the same clinically based and multiple regression models used in a previous study of age estimation from private dental practice patients in which the long-cone radiographic technique had been used. Age estimation for both models was based on the same radiographic parameters used in that previous study (13 for the clinical model and eight for the regression model). Results showed that, in contrast to that previous study, the clinical model was superior to the regression model. Mean difference between estimated and actual age was +/- 4.4 years (clinical) and +/- 6.3 years (regression). Median difference between estimated and actual age was +/- 2.0 years (clinical) and +/- 6.0 years (regression). Mode difference between estimated and actual age was +/- 2.0 years (clinical) and +/- 6 and 7 years (regression). The results from the present study show that the clinical and regression models developed from full-mouth series of periapical radiographs taken of living patients by the long-cone radiographic technique can be used with decedents' radiographs taken with the bisecting-angle technique. PMID- 7879774 TI - Zulu zip-guns and an unusual murder. AB - Primitive ballistic weapons are used in great numbers in Zululand, South Africa. Their manufacture reflects various degrees of skill. A case with a bullet and a cartridge in the victim is discussed, and a representative pictorial exhibition of weapons is presented. PMID- 7879775 TI - Primer residues deposited by handguns. AB - There is much anecdotal information being disseminated, even offered in expert witness testimony, concerning the deposit of primer residues on the hands of persons in front of the muzzle of handguns. We present data for 9 mm and 380 Auto pistols and for a 38 caliber revolver depicting the procedure for obtaining wipings taken from targets representing the hands of a gunshot victim. These wipings from pork tissue were then analyzed for the primer residue metals antimony, barium, and lead. The data show that the two primary metals, antimony and barium, are deposited on the targets out to 4 feet for the pistols and out to three feet for the 38-caliber revolver. Testing will continue in actual cases with the gun and ammunition involved in the shooting. PMID- 7879776 TI - Racial and ethnic patterns in firearms deaths. AB - In the United States, there is currently an epidemic of firearms violence. Among victims of this violence, there are striking racial and ethnic patterns in the manners and circumstances of death. This study was conducted to explore and quantitate some of these differences. Autopsy and investigation reports of 554 consecutive firearms deaths in Dallas County, Texas, from March 1992 to February 1993 were reviewed. Overall suicide rates by race for 1970 and 1990 were calculated. Suicide rates for blacks have increased while overall rates (all races) have decreased slightly. Large racial and ethnic differences in the homicide-suicide ratio (H:S) were found (0.42 in non-Hispanic whites; 7.44 in others) (p < 0.001). Non-Hispanic whites who committed suicide with a firearm were less likely than other groups to do so with another person present (12% non Hispanic whites; 49% others) (p < 0.001). Blacks and Asians who committed suicide with a firearm killed another person in 67% of witnessed cases (those with another person present during the incident). Whites (Hispanics and non-Hispanics) killed another person in only 12% of witnessed firearm suicides. The data suggest that the subtypes, psychodynamics, and causes of suicide may currently differ among racial and ethnic groups. These differences should be considered in order to formulate adequate prevention strategies and to assess the suicide and homicide risk in depressed individuals. The difficulty of accurate death certification in some cases is also discussed. PMID- 7879777 TI - A century of forensic service in Bulgaria. AB - Forensic medicine first developed in Bulgaria alongside the legal curriculum. Forensic services were established as early as 1883, following the liberation of Bulgaria from the Ottoman Empire. The first lecture on forensic medicine was given to students of the law faculty in Sofia in 1894. In 1917, the first Department of Forensic Medicine was established as part of the medical faculty in Sofia. This article describes the Bulgarian system of district forensic services, as well as the educational and research programs of the current medical faculties. PMID- 7879778 TI - An unusual case of maternal-fetal death due to vaginal insufflation of cocaine. AB - Air embolism secondary to vaginal insufflation has been documented as a cause of death in pregnant women. Under pressure, the air enters the uterus, causing air emboli within the uterine venous drainage and subsequently the systemic circulation. Death is usually sudden as the air obstructs the normal flow of circulation. Acute cocaine toxicity is also a well-known cause of sudden death. Cocaine use is prevalent in our society, even among pregnant women. We report the sudden death of a 31-year-old gravid female and 39-week gestational age male fetus. The cause of death was air embolism secondary to oral-vaginal insufflation of cocaine smoke. PMID- 7879779 TI - Homicidal strangulation by victim's own hair presenting as natural death. AB - We report an unusual case of homicidal strangulation of a healthy woman using her own head hair as the ligature. An attempt was made by the accused murderer to mask the homicide. Autopsy findings are presented that emphasize the lack of injuries to the deep neck structures when a soft, broad ligature is used. This case also highlights the difficulties arising in interpretation of pathological findings in asphyxial deaths, when the circumstances are not available and the ligature is not in place. Review of the English language literature found no similar case. PMID- 7879780 TI - Homicide-associated burning in Cape Town, South Africa. AB - To describe the features of homicide-associated burnings (HAB) and examine factors that distinguish between intentional and accidental fatal burn injury, we undertook a review of all burn cases admitted to the Salt River State Mortuary, Cape Town, South Africa, between January 1, 1991, and December 31, 1992. Of 358 burn-related deaths, 35 (10%) were homicides; five (14%) of these were described as "necklacings." No significant difference existed in age, sex, residential status, or extent of burn injury between the HAB and adult residential fire victims (ARFV). Of the HAB, 44% had soot in the trachea and main bronchi, whereas soot was present in 83% of the ARFV (p = 0.001). The median blood carbon monoxide saturation was 12% in the HAB and 30% in the ARFV (p = 0.001). Of the HAB, 48% had a blood alcohol concentration > 0.1 g/100 ml, whereas this concentration was noted in 70% of ARFV (p = 0.02). Evidence of either gunshot, stabbing, or blunt force injury was seen in 82% of the HAB. Although some significant autopsy parameters characterize HAB, we conclude that the forensic pathologist should diligently seek evidence of homicidal injury in all fatal burn cases. PMID- 7879781 TI - The authors' response. PMID- 7879782 TI - Subendocardial hemorrhages. PMID- 7879783 TI - The distribution of incubation periods of infectious disease. 1949. AB - 1. Characteristics of the distribution of incubation periods of a number of infectious diseases, as reported in the literature, have been reviewed. 2. The usual frequency curve of incubation time takes the form of a logarithmic normal curve. This appears to be equally true of diseases with very short and very long incubation periods. 3. The measure of variation in incubation periods used in this study, termed the dispersion factor, is the antilogarithm of the logarithmic standard deviation. Dispersion factors for most of the diseases studied range from 1.2 to 1.5 and are independent of mean length of incubation. 4. Some epidemiological uses for a knowledge of the distribution of incubation time are discussed. PMID- 7879784 TI - The spectrum of medical conditions and symptoms before acquired immunodeficiency syndrome in homosexual and bisexual men infected with the human immunodeficiency virus. AB - The full range and occurrence of medical conditions in persons infected with human immunodeficiency virus (HIV) before they develop illnesses that define acquired immunodeficiency syndrome (AIDS) have not been systematically or completely described. In a retrospective and prospective cohort study, 1,073 homosexual and bisexual men in three US cities were interviewed and examined twice per year from January 1988 to September 1992. Study participants were from San Francisco, California (273 HIV-seropositive and 432 HIV-seronegative men), Denver, Colorado (107 positive and 129 negative men), and Chicago, Illinois (54 positive and 78 negative men). A total of 305 HIV-positive men had specifiable dates of HIV seroconversion (mean of 15.3 months between the last negative and the first positive HIV antibody test). Besides much increased incidences of thrush (incidence relative risk (IRR) = 23.3) and hairy leukoplakia (IRR = 551), the following conditions also occurred significantly more frequently in HIV positive men than in HIV-negative men: anal herpes (incidence density (ID) = 10.7/100 person-years; IRR = 7.7); sinusitis requiring antibiotics (ID = 6.2/100 person-years; IRR = 2.1); anal warts (ID = 5.8/100 person-years; IRR = 2.7); seborrhea (ID = 3.8/100 person-years; IRR = 6.6); community-acquired pneumonia (ID = 1.4/100 person-years; IRR = 2.7); skin cancers (ID = 1.0/100 person-years; IRR = 2.2); and seizures, often apparently "breaking through" prior anticonvulsant therapy (ID = 0.8/100 person-years; IRR = 5.6). First episodes of hairy leukoplakia, thrush, and skin cancer occurred at low mean CD4 counts (mean counts were less than 350 cells/microliters) and late in HIV infection (mean times were more than 8 years after HIV seroconversion). Many medical problems, some not widely appreciated, occur in HIV-infected men before they develop AIDS defining illnesses, signifying considerable morbidity from pre-AIDS HIV infection. PMID- 7879786 TI - Cigarette smoking and spontaneous abortion of known karyotype. Precise data but uncertain inferences. AB - Data from the first phase (1974-1979) of this New York City case-control study showed that 1) cigarette smoking during pregnancy was associated positively with chromosomally normal spontaneous abortion and 2) both past and current smoking were associated inversely with trisomic loss in women under age 30 years and positively in older women. The authors used data from two subsequent study phases (1979-1982 and 1982-1986) to test the stability of these associations over time and the homogeneity between payment groups (private vs. public). Spontaneous abortions (cases) were classified as chromosomally normal (n = 1,388), trisomic (n = 557), or other chromosomally aberrant (n = 409). Controls (n = 4,165) were women who had registered for prenatal care before 22 weeks' gestation and delivered at 28 weeks or later. For chromosomally normal loss, later data gave modest support to prior observations. In the total sample, current smoking (defined as smoking during the month of the last menstrual period) of 14 or more cigarettes per day was increased among chromosomally normal cases in comparison with controls (adjusted odds ratio (OR) = 1.3, 95% confidence interval (CI) 1.1 1.7) and in comparison with other aberrant cases (adjusted OR = 1.2, 95% CI 0.8 1.8). Stronger associations in public patients than in private patients (adjusted odds ratios of 1.4-1.5 versus 0.8-0.9, respectively) might indicate either a mediating effect of social disadvantage or a chance fluctuation. For trisomic loss, later data did not support prior observations. Associations between trisomy and past or current smoking did not vary significantly with age in either payment group; assuming no effect modification of age, adjusted odds ratios for smoking in relation to trisomy were 0.9-1.0. PMID- 7879785 TI - Lactose and galactose intake and metabolism in relation to the risk of epithelial ovarian cancer. AB - It has been suggested that aspects of lactose consumption and metabolism favoring a relatively high tissue level of galactose-1-phosphate may predispose women to ovarian cancer. The authors sought to examine this hypothesis in a study of 108 18- to 74-year-old Caucasian residents of a three-county area of western Washington who were diagnosed with stage I ovarian cancer during 1989-1991, and 108 age- and race-matched controls. Lactose and galactose intake, measured using a food frequency questionnaire, had been hypothesized to increase risk, but were somewhat lower among the cases than among the controls (75th percentile of lactose intake vs. 25th: odds ratio (OR) = 0.80, 95% confidence interval (Cl) 0.52-1.2; of galactose intake: OR = 0.71, 95% Cl 0.48-1.1). Intestinal lactase activity, also hypothesized to have a positive relation with ovarian cancer occurrence, was measured with an oral lactose challenge followed by determination of urinary galactose; no evidence that it was related to the disease was found (75th percentile of excreted galactose vs. 25th: OR = 0.87, 95% Cl 0.62-1.2). Galactose-1-phosphate uridyltransferase (transferase), the enzyme responsible for the metabolism of galactose-1-phosphate, was measured in erythrocytes; no deficit in cases was observed (75th percentile of transferase activity vs. 25th: OR = 1.3, 95% Cl 0.80-2.1). There was also no excess of cases carrying low-activity genetic variants of the transferase enzyme (lower-activity variants vs. higher activity variants: OR = 0.61, 95% Cl 0.21-1.7). These results do not support the hypothesis that aspects of lactose and galactose intake and metabolism have a bearing on the etiology of ovarian cancer. PMID- 7879788 TI - Relations between antioxidant vitamins in adipose tissue, plasma, and diet. AB - For an evaluation of fat-soluble vitamin concentrations in adipose tissue as biomarkers of intake, estimates of usual intake of beta-carotene, total vitamin A, and vitamin E (assessed by food frequency questionnaire) were compared with plasma and adipose tissue concentrations of beta-carotene, retinol, and alpha tocopherol, respectively. Data were collected in 1992 in the Netherlands for 85 healthy, nonsmoking volunteers aged 50-70 years (38 males and 47 females). For alpha-tocopherol, a significant age- and sex-adjusted partial correlation (r = 0.24, p < 0.05) was observed between adipose tissue levels and intake. For beta carotene, the partial r was 0.20. Adipose tissue retinol did not reflect intake (partial r = 0.08). Correlations of adipose tissue vitamin levels with plasma vitamin levels were higher overall (r = 0.34 for alpha-tocopherol, r = 0.56 for beta-carotene, and r = 0.17 for retinol) than correlations with intake. Plasma concentrations of alpha-tocopherol, beta-carotene, and retinol were not associated with dietary intake (partial r's were 0.05, 0.17, and -0.12, respectively). Pearson correlations of repeated measurements in adipose tissue (after 4 months) were 0.24 for retinol, 0.50 for beta-carotene, and 0.78 for alpha-tocopherol. Adipose tissue beta-carotene was shown to increase sixfold after 6 months' supplementation with 30 mg of beta-carotene daily. It is concluded that adipose tissue vitamin concentrations are an acceptable alternative to plasma levels as relatively stable indicators of dietary intake. However, both plasma and adipose tissue levels are more useful as markers of internal dose, taking into account variations in absorption and metabolism, than of dietary intake. PMID- 7879787 TI - Cardiovascular risk factors among third grade children in four regions of the United States. The CATCH Study. Child and Adolescent Trial for Cardiovascular Health. AB - Data on cardiovascular risk factors (body mass index, triceps and subscapular skinfolds, blood pressure, serum total cholesterol, high density lipoprotein (HDL) cholesterol, and apolipoprotein B) were collected as part of the baseline examination (fall 1991) of the Child and Adolescent Trial for Cardiovascular Health, a multicenter school-based intervention study for promoting healthful behaviors. A total of 5,106 third grade children (mean age, 8.76 years) in four states (California, Louisiana, Minnesota, and Texas) were examined. After excluding 194 children of other or unknown origin, the study population consisted of 3,530 Anglo-American children, 674 African-American children, and 708 Latino children. African-American children were the tallest by 1-3 cm (p < 0.0001), while Latino children had the largest body mass index (p < 0.05). Blood pressure levels were similar for boys and girls and among the three races, but systolic levels were 2 mmHg higher in Texas than at the other sites. Serum total cholesterol levels were 5 mg/dl higher in girls than in boys (p < 0.05), while HDL cholesterol levels were 2 mg/dl higher in boys (p < 0.05). HDL cholesterol levels were highest in African-Americans (55.5 mg/dl) compared with Anglo Americans (50.7 mg/dl) and Latinos (51.3 mg/dl) (p < 0.0001). PMID- 7879789 TI - Spouse support and long-term adherence to lipid-lowering diets. AB - Social support is inversely associated with heart disease risk. Support may influence heart disease by encouraging health behavior change in high-risk individuals. This study examined the association between spouse support and maintenance of low-fat diets in men with hypercholesterolemia. Participants were 254 men enrolled in a 24-month randomized trial of lipid-lowering diets initiated in 1985 in Seattle, Washington. The Evaluation of Spouse Support, which assesses the extent to which spouses supported maintenance of lipid-lowering diets, was administered after the last of eight dietary classes and at 3, 12, and 24 months postinstruction. Attainment of dietary goals was determined from food records completed at the end of the class and at 3, 12, and 24 months. Compared with those in the lowest quartile, those in the highest quartile of support were more likely to attain dietary goals at 3 months (odds ratio (OR) = 4.5, 95% confidence interval (CI) 1.9-10.4), 12 months (OR = 5.5, 95% CI 2.4-12.5), and 24 months (OR = 3.9, 95% CI 1.7-9.3). Support was not associated with end-of-class dietary goal achievement. Social support may be an important factor in the maintenance of low fat diets. PMID- 7879790 TI - Weight variability effects: a prospective analysis from the Stanford Five-City Project. AB - For determination of the effects of weight variability on cardiovascular risk factors, a random community sample of 269 men and 361 women aged 25-74 years, drawn from the Stanford Five-City Project, was followed for up to 10 years (1979 1989). Systolic and diastolic blood pressure, total and high density lipoprotein cholesterol, and pulse were measured. Body mass index slope (BMI-slope) was determined by regressing five BMI values on time for each individual. BMI variability was defined as the root mean square error (BMI-RMSE) of a regression line fitted to each individual's BMI values over time. The slopes of the five cardiovascular risk factors were most strongly related to the baseline value of each risk factor and BMI-slope in both men and women. Neither BMI-RMSE nor the interaction of BMI-RMSE with BMI-slope was related to risk factor slopes. In this population, BMI variability had little impact on cardiovascular risk factors compared with BMI-slope and baseline BMI. PMID- 7879791 TI - Competing causes of death: an analysis using multiple-cause-of-death data from The Netherlands. AB - The standard methodology for cause-elimination life tables assumes that the various causes of death are statistically unrelated to one another, so that the mortality risks of those who are saved from an eliminated cause equal the risks of dying from other causes which are observed for the general population. In the analysis reported in this paper, data on multiple causes of death for the year 1990 in the Netherlands were used to investigate whether this is likely to be a valid assumption. For four groups of underlying causes of death (malignant neoplasms, cardiovascular diseases, and external causes), the age-standardized prevalence at death of other conditions was calculated. Two series of calculations were performed: one with all other coded conditions present at death and one with a selection of conditions that were eligible to become the new underlying cause of death after the present underlying cause had been eliminated. The results suggested that there are major differences between underlying causes of death in the prevalence at death of other conditions. According to the second series of calculations, the prevalence at death of other conditions. According to the second series of calculations, the prevalence of possible new underlying causes of death was relatively high among persons who died from cardiovascular diseases; about average for persons who died from respiratory diseases; and relatively low for persons who died from malignant neoplasms and external causes. Although studies validating the multiple-cause-of-death data as they appear in the official statistics are necessary, these results reconfirm that this is a potentially rich source of information and that the assumption made in conventional cause-elimination life tables is unlikely to be valid. PMID- 7879792 TI - Re: "Total serum testosterone and gonadotropins in workers exposed to dioxin". PMID- 7879793 TI - Re: "Total serum testosterone and gonadotropins in workers exposed to dioxin". PMID- 7879794 TI - Re: "Alcohol, smoking, coffee, and cirrhosis" and "coffee and serum gamma glutamyltransferase: a study of self-defense officials in Japan". PMID- 7879795 TI - New project launched to track antibiotic resistance. PMID- 7879796 TI - Expanded government program for childhood immunizations begins. PMID- 7879797 TI - Acute liver failure linked to felbamate use. PMID- 7879798 TI - Proposed safety measures aimed at protecting children from iron poisoning. PMID- 7879799 TI - Pharmacists in California HMOs gain expanded role. PMID- 7879800 TI - Delaware State Society helps mold law on nurse prescribing. PMID- 7879801 TI - Hassle-free documentation of work activities. PMID- 7879802 TI - Patient autonomy and drug therapy adherence. PMID- 7879803 TI - Antipsychotic drug use in older adults. AB - The pharmacology, pharmacokinetics, drug interactions, adverse effects, indications for use, efficacy, dosage, and pattern of use of antipsychotics in adults older than 65 years are reviewed. Most available antipsychotic agents block dopamine type 2 postsynaptic receptors. Antipsychotics also bind to cholinergic, alpha-adrenergic, histamine type 1, and serotonin receptors. The affinities of a given agent for receptors determine its adverse effects and probably its efficacy. There are many obstacles to therapeutic drug monitoring. Many antipsychotics are metabolized into multiple active compounds. Drug clearance from brain tissue may be slower than from plasma. Therapeutic steady state concentrations are difficult to define. Age-related physiological changes alter the pharmacokinetic and pharmacodynamic characteristics of antipsychotics, placing the elderly adult at heightened risk for adverse effects. Agents that may interact with the antipsychotics include carbamazepine, phenytoin, phenobarbital, tricyclic antidepressants, and lithium. Adverse effects frequently observed in the elderly are orthostatic hypotension, anticholinergic effects, pseudoparkinsonism, and tardive dyskinesia. Neuroleptic malignant syndrome is a rare but potentially fatal reaction. The antipsychotics carry approved labeling for use in treating psychotic disorders; many antipsychotics are approved for use in treating other conditions as well, such as behavioral problems. The Omnibus Budget Reconciliation Act of 1987 established dosage and documentation guidelines for antipsychotic drug use in residents of nursing homes. The guidelines specify that antipsychotics should not be used in this population if the only indication is a problem behavior like wandering. Although antipsychotics are often prescribed for behavioral control in older adults, most studies show only modest efficacy, while some show worsening of symptoms. As-needed orders for antipsychotics are controversial. Antipsychotics can relieve symptoms in the older adult, but lower dosages and more frequent assessments are necessary than for younger adults. PMID- 7879804 TI - Overview of the New York State program for prescription drug benefits. AB - New York State's prescription drug benefits program is described. The Empire Plan, a part of the New York State Health Insurance Program, includes a prescription drug benefits program. The prescription drug program began in 1986 and covers more than 700,000 people. In 1988 the state started a therapeutic drug use-evaluation (DUE) program in correct with the supplier, Health Information Designs, a subsidiary of ValueRx Pharmacy Program. In 1991 the partnership with ValueRx was expanded to include patient profilling and physician education. In 1993 the state implemented a prior-authorization program for certain high technology drugs, also administered by ValueRx. New York's public work force is heavily unionized, and the unions have been deeply involved in program design and vendor selection. Program participants have access to a large network of community pharmacies. The program also provides mail-order service. Quality is at the center of the state's and the unions' prescription drug program philosophy. Saving money is also a major objective; savings totaling $19.5 million were realized from 1988 through 1993 under the partnership between the state and ValueRx. The Empire Plan's prescription drug benefits program is building quality and saving money by integrating DUE, prior authorization, education, community pharmacy, and mail-order service. PMID- 7879805 TI - Hospitalwide medication policies and standards. AB - The development and composition of a hospitalwide medication policies and standards manual are described. Medication policies and procedures developed independently by individual hospital departments and services at a 789-bed private teaching institution created problems related to consistency, the approval process, accreditation standards, and retrievability. Therefore, a joint nursing-pharmacy task force was formed to create a master document containing medication policies and standards for the entire institution. The manual also contains departmental medication-related procedures, the formulary of approved drugs, and key drug information. Its format allows for periodic updating and ease of use by nurses, pharmacists, physicians, and other health care professionals. It meets the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) requirement of a collaborative framework to ensure optimal medication-use outcomes. All medication-related procedures in individual departments must comply with the new policies and standards. A hospitalwide medication policy manual, created through multidisciplinary collaboration, made the policies and procedures consistent and more accessible and met JCAHO and other regulatory requirements. PMID- 7879806 TI - Reduced use of lower-osmolality contrast media resulting from an order form and guidelines. PMID- 7879807 TI - Stability of mesalamine in rectal suspension diluted with distilled water. PMID- 7879808 TI - Compatibility of haloperidol lactate with benztropine mesylate. PMID- 7879809 TI - Incompatibility of ketorolac tromethamine with haloperidol lactate and thiethylperazine maleate. PMID- 7879810 TI - Metrizamide-ethanol for treatment of symptomatic vascular malformations. PMID- 7879811 TI - Inaccuracy in fluoxetine comparison. PMID- 7879812 TI - Information on drop size needs to be eyed closely. PMID- 7879813 TI - Re-examination of clinical aspects of pharmacoeconomic analysis. PMID- 7879814 TI - National health care reform, Part 1: Why it fizzled. PMID- 7879815 TI - Sarcoidosis: linking inflammation and fibrosis. PMID- 7879816 TI - Distribution of extracellular matrices, matrix receptors, and transforming growth factor-beta 1 in human and experimental lung granulomatous inflammation. AB - Aberrant deposition of extracellular matrices (ECMs) may affect lung inflammation by influencing cell adhesion, migration, and activation. Little is known about the expression of ECMs in lungs with granulomatous inflammation. Therefore the authors investigated the distribution of ECMs, matrix receptors of the integrin family, and transforming growth factor-beta 1 (TGF-beta 1) in lungs from patients with pulmonary sarcoidosis and animals with experimental granulomatosis. Immunohistochemistry revealed increased deposition of type I collagen and fibronectin in human lung granulomas when compared with healthy human lungs. Procollagen type I and cellular fibronectin also were increased, suggesting local synthesis of ECM in sarcoid granulomas. These findings were accompanied by increased staining for fibronectin (alpha 5 beta 1) and collagen (alpha 2 beta 1) integrin receptors. The matrix-inducing cytokine TGF-beta 1 was co-distributed with the aforementioned molecules in the granulomas, whereas no significant staining for TGF-beta 1 was found in healthy lungs. Similar to sarcoid lungs, analysis of lung sections obtained from a murine model of granuloma formation revealed increased expression of fibronectin, collagen, integrin receptors, and TGF-beta 1 within granulomas. Based on these observations, there is increased expression of ECM and matrix receptors in both human and experimental lung granulomas. Such alterations may influence the recruitment and activation of inflammatory cells and fibroblasts, promoting granuloma formation and remodeling of tissue by fibrosis. Activation of mononuclear cells resulting in production of TGF-beta 1 is likely to contribute to the changes described. PMID- 7879817 TI - Low-dose oral glyburide reduces fasting blood glucose by decreasing hepatic glucose production in healthy volunteers without increasing carbohydrate oxidation. AB - Glyburide is an effective hypoglycemic agent in patients with type II diabetes even after the loss of its ability to increase insulin secretion. The exact mechanism is unknown. In an attempt to describe the direct effect of glyburide on glucose metabolism, a very low dose of glyburide (20 micrograms/kg body weight) was given orally to 12 healthy volunteers in an attempt to increase blood concentrations of the drug without causing a marked increase in insulin secretion. Fasting hepatic glucose production (HGP), carbohydrate oxidation (CO), leucine appearance, leucine oxidation, and fat oxidation were determined between hours 3 and 4 and hours 7 and 8. The changes seen in the glyburide-treated volunteers were compared with the changes seen in 5 non-treated, healthy volunteers during the same 8-hour period. Mean blood glucose decreased greater in the glyburide-treated volunteers (20 +/- 2% vs 5 +/- 2%, P < 0.01). Insulin and C peptide concentrations after glyburide administration (hour 7 to 8) did not differ significantly from baseline (hour 3 to 4) values (insulin: 53 +/- 9 pmol/L vs 52 +/- 9 pmol/L; C-peptide: 0.34 +/- 0.06 ng/mL vs 0.39 +/- 0.07 ng/mL). This low dose of glyburide resulted in a significantly greater decrease in HGP (16 +/- 2%; P < 0.001) than seen with fasting alone (8 +/- 4%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879818 TI - Alteration of adenosine triphosphate and other nucleotides after sublethal oxidant injury to rat type II alveolar epithelial cells. AB - The alveolar epithelial cells of the lower respiratory tract are continuously exposed to injurious agents, including oxygen radicals. The type II alveolar epithelial cell is critically important to the normal function of the lung, because it is responsible for synthesis of surfactant and other essential duties. The present investigation measured the level of intracellular nucleotides and adenosine over time after exposure of type II cells to sublethal concentrations of physiologically relevant oxidants, hydrogen peroxide and hypochlorous acid (HOCl). Initially, it was determined that 250 microM HOCl or 250 microM hydrogen peroxide could each cause sublethal injury to the type II cells after exposure of up to 1 and 2 hours, respectively. After exposure to 250 microM hydrogen peroxide, the intracellular levels of adenosine, adenosine diphosphate, and adenosine triphosphate all initially increased in the first 1 to 15 minutes, but subsequently decreased significantly, ultimately reaching close to 40% below control levels. The level of adenosine monophosphate remained significantly elevated throughout the exposure until returning to control levels after 2 hours. Similar results occurred after the type II cells were exposed to 250 microM HOCl. This study demonstrates that adenosine triphosphate and other cellular nucleotides and nucleosides were decreased in type II cells before lethal injury and subsequent cell death. PMID- 7879819 TI - Effect of absorption of D-glucose and water on paracellular transport in rat duodenum-jejunum. AB - Paracellular transport is thought to be a major absorptive pathway for small nutrient molecules. The authors used in vivo in situ perfusion of rat duodenum proximal jejunum to examine paracellular transport using lactulose as a probe. They perfused solutions with a constant lactulose concentration but varied initial D-glucose concentration (range 12-176 mM) to open paracellular pathways and to increase water absorption, thereby optimizing potential for paracellular transport of lactulose and other solutes in its molecular weight range. All solutions contained sodium chloride to approach isotonicity. Water absorption was measured as the difference in weight of solution perfused and sample collected. Absorption of D-glucose increased with mean luminal D-glucose concentration, and water absorption more than doubled (from 0.12 +/- 0.03 to 0.26 +/- 0.05 mL/min per g dry wt of segment) as mean luminal glucose concentration was increased from 10 to 80 mM. Lactulose absorption was at the threshold of detection and did not correlate with D-glucose or water absorption. Expressed as percent per segment, D glucose absorption ranged from 29-50%, and the lactulose absorption rate was 4 5%. The fraction of D-glucose absorption that could be attributed to lactulose absorptive pathways was 12% at the highest rate of water absorption. In conclusion, based on lactulose as a probe, under conditions of opening tight junctions by D-glucose, the paracellular component of D-glucose absorption was of the order of 1/10 of total D-glucose absorption (ie, not a major absorptive pathway. PMID- 7879820 TI - Refractory and relapsing multiple myeloma treated by blood stem cell transplantation. AB - Between June 1989 and June 1992, 12 patients with advanced multiple myeloma underwent peripheral blood stem cell autotransplantation after high-dose chemotherapy and radiotherapy. The conditioning regimen included melphalan (140 mg/m2), high-dose cyclophosphamide (120 mg/kg), methylprednisolone (2 g daily x 7), and total body irradiation (9-12 Gy). Transplant morbidity included severe mucositis (n = 7) and acute renal failure (n = 2) related to infusion of the stem cells. Engraftment was delayed (n = 4) in this heavily pretreated population, and two patients had complete graft failure. Despite the advanced nature and chemotherapy-refractory state of their disease, 11 of 11 evaluable patients achieved an objective response. Six patients survived to leave the hospital, and four remain alive--one died of acute leukemia induced by prior melphalan exposure. Three of the four are relapse-free at a median of 24.9 months (range, 18-28 months). Some patients with advanced refractory multiple myeloma can achieve objective responses from highdose chemoradiotherapy with peripheral blood stem cell rescue. Harvesting peripheral blood stem cells from high-risk patients early in their disease for later use may decrease the risk of graft failure. Peripheral blood stem cell transplantation after high-dose chemotherapy and total body irradiation can produce durable responses in patients with advanced refractory myeloma. PMID- 7879821 TI - High-dose dexamethasone suppression testing versus inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin-dependent Cushing's syndrome: a decision analysis. AB - Differentiation of adrenocorticotropin (ACTH)-dependent Cushing's syndrome between Cushing's disease and the occult ectopic ACTH syndrome is difficult. Simultaneous bilateral inferior petrosal sinus sampling (IPSS) for ACTH levels in response to corticotropin-releasing hormone has high diagnostic accuracy, but its cost-effectiveness has not been analyzed. In this study, decision analysis was used to compare two diagnostic strategies: IPSS versus high-dose dexamethasone suppression (HDD) followed by IPSS in those with a negative HDD test. Sensitivity analyses were performed for all variables. The authors found that at 100% accuracy, IPSS has an incremental cost-effectiveness ratio of $1,000,000 per life saved. Incremental cost, incremental effectiveness, and incremental cost effectiveness are sensitive to the pretest probability of Cushing's disease, test characteristics, and test costs. As the pretest probability of Cushing's disease decreases, cost per life saved also decreases to less than 85%, the HDD strategy saves more lives and costs less. When the HDD test has a 83% sensitivity rate and a 100% specificity rate, the two strategy remains less expensive. The IPSS strategy saves lives whenever HDD specificity is less than 100%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879823 TI - Case report: intraglomerular metastasis with neoplastic cell interposition. AB - A case is described of an 88-year-old man with lung cancer, nephrotic syndrome, and renal dysfunction who died suddenly of an acute myocardial infarction and whose autopsy revealed many adenocarcinoma cells stacked within glomerular capillary lumina of his kidney, entering into basement membrane zones (ie, neoplastic cell interposition). In addition, glomeruli showed a lobular transformation, doubling of glomerular basement membrane, and electron dense deposits along the glomerular basement membrane. These changes were similar to those of membraneoproliferative glomerulonephritis. The association of intraglomerular metastasis and membranoproliferative glomerulonephritis-like lesions led the authors to speculate that the latter glomerular change might have provided an attractive opportunity for circulating tumor cells to be trapped and grow within the glomerular lumina. This mode of metastasis has not been well recognized. The authors describe the experience, review the literature, and discuss its possible pathogenesis. PMID- 7879822 TI - T cell receptor gamma gene polymorphisms and class II human lymphocyte antigen genotypes in patients with celiac disease from the west of Ireland. AB - Although celiac disease has one of the strongest human lymphocyte antigen (HLA) class II associations of any human illness, it is clear that at least one gene that is not linked to the HLA region also is required for its pathogenesis. The occurrence of large numbers of gamma delta T cells in the bowel mucosa of patients and the recent description of T cell receptor (TCR) gamma chain polymorphic variants identified by restriction fragment length polymorphism analysis led the authors to examine TCR gamma genotypes in relation to HLA-DR, DQ genotypes in 89 patients with celiac disease and 55 control subjects from the West of Ireland. The overall frequency of TCR gamma genotypes in patients and control subjects was comparable. However, most of the patients had 1 of 3 HLA-DR3 genotypes (DR3/15, 3/7, or 3/3), and there was a significant alteration of the expected frequency of TCR gamma genotypes among patients with these three genotypes. The major differences were an increased association of HLA-DR3 homozygosity, with TCR gamma genotypes having a 16.0 kb fragment and an increased frequency of DR3/7 heterozygosity and decreased frequency of DR3/15 heterozygosity, respectively, in association with the TCR gamma 13.0/11.3 kb genotype. Based on their results, there is the possibility that an interaction between the products of two polymorphic and unlinked gene regions contributes to the pathogenesis of celiac disease. PMID- 7879824 TI - Case report: poorly differentiated carcinoma of unknown primary presenting as Trousseau's syndrome. AB - Two patients without clinical evidence of malignancy had idiopathic migratory thrombophlebitis. A clinical state consistent with Trousseau's syndrome prompted a work-up of each patient for occult cancer. In both individuals, computed tomography of the chest revealed a solitary mediastinal lymph node that, though inconspicuous, was evaluated further because of the clinical picture. Mediastinoscopy with biopsy revealed poorly differentiated carcinoma. Treatment was begun for carcinoma of unknown primary with variable response to therapy. The clinical presentation and pathophysiology of Trousseau's syndrome, as well as its use in leading to an antemortem diagnosis of occult cancer in these and other patients, are delineated. PMID- 7879825 TI - Case report: congenital absence of the left pulmonary artery accompanied by ipsilateral emphysema and adenocarcinoma. AB - Unilateral absence of the left pulmonary artery is a rare congenital anomaly that may remain unrecognized until adulthood, in which case it may lead to inappropriate diagnosis and management. The authors describe a case in which a patient came to their institution with dyspnea and a chest roentgenogram showing a prominent right pulmonary artery, right aortic arch, and a left lung mass accompanied by ipsilateral volume loss. Although the initial evaluation suggested a differential diagnosis that included thromboembolic pulmonary disease and vascular compression by tumor, further workup revealed unilateral absence of the left pulmonary artery accompanied by left lung hypoplasia, and interestingly, ipsilateral emphysema and adenocarcinoma. The embryologic factors responsible for this abnormality and how it may potentially affect the development of emphysema and adenocarcinoma are discussed. PMID- 7879826 TI - Is routine contralateral exploration advisable for children with unilateral inguinal hernias? PMID- 7879827 TI - Divide and conquer--protection, comfort, and cost of the surgeon's gown. PMID- 7879828 TI - Pancreas Club meeting, May 15, 1994, New Orleans, Louisiana. PMID- 7879829 TI - Amelioration of intestinal dysmotility and stasis by octreotide early after small bowel autotransplantation in dogs. AB - BACKGROUND: Intestinal dysmotility and stasis after intestinal transplantation are considered to promote bacterial overgrowth and translocation. Two prokinetic agents, KW5139 (13-leu-motilin) and the somatostatin analogue octreotide acetate, were studied to determine whether they can ameliorate intestinal dysmotility during the early postoperative period. MATERIALS AND METHODS: Motility was recorded by multiple extraluminal strain-gauge transducers in 6 dogs on postoperative days 1, 3, 7, and 14. A barium meal study was performed with a separate group of 8 dogs on postoperative days 3 and 7. RESULTS: The agent KW5139 induced brief, weak contractions in the graft and had little effect on the dilated bowel; however, octreotide induced motor activity that propelled accumulated intestinal contents into the colon and reduced dilation of the transplanted bowel. CONCLUSION: Octreotide, but not KW5139, ameliorates intestinal dysmotility associated with bowel autotransplantation during the early postoperative period. Short-term administration of octreotide may be useful for the treatment of dysmotility following intestinal transplantation. PMID- 7879830 TI - Hepatic functional reserve in patients with obstructive jaundice: an assessment by the redox tolerance test. AB - PURPOSE: Hepatic mitochondrial response to oral glucose load (redox tolerance test) was evaluated as an indicator of hepatic functional reserve of patients with obstructive jaundice. PATIENTS AND METHODS: The redox tolerance test was performed in 29 patients with obstructive jaundice before percutaneous transhepatic biliary drainage and 2 weeks after the procedure. RESULTS: The redox tolerance index (RTI) before drainage was not related to conventional parameters other than albumin, but was significantly associated with bilirubin half-life (P < 0.01). Of 19 patients with an RTI > or = 0.5 before drainage, all maintained similar values after drainage and experienced satisfactory clinical courses, even after major surgery. Of 10 patients with an RTI < 0.5 before drainage, 5 showed improvement and 5 deteriorated after drainage. Four of the latter 5 died within 60 days after drainage. The hospital mortality was significantly greater in patients with initial RTI < 0.5 than in patients with RTI > or = 0.5 (P < 0.01). CONCLUSION: The redox tolerance test is useful for evaluating hepatic functional reserve and prognosis in patients with obstructive jaundice. PMID- 7879831 TI - Multivariate analysis of risk factors for postoperative pneumonia. AB - PURPOSE: Many risk factors for postoperative pneumonia have been identified, but those for the progression from atelectasis to pneumonia have been poorly examined. We undertook the present study to find risk factors for the progression from atelectasis to pneumonia. PATIENTS AND METHODS: We completed a retrospective analysis of 2,969 patients who underwent major abdominal surgery during the past 13 years. RESULTS: Pneumonia developed in 45 patients (1.5%), and postoperative atelectasis with a high risk for the subsequent infection occurred in 44 patients in whom pneumonia did not develop. A series of 13 variables was compared in the two patient categories. By multivariate discriminant analysis, we identified three independent significant correlates of the development of postoperative pneumonia: blood loss of more than 1,200 mL during surgery, age over 65 years, and preoperative utilization of inhalation therapy devices. CONCLUSION: This study shows that a substantial number of cases of postoperative pneumonia can be prevented. PMID- 7879832 TI - Cross-filling of circle of Willis and carotid stenosis by angiography, duplex ultrasound, and oculopneumoplethysmography. AB - PURPOSE: To evaluate the filling of the Circle of Willis on preoperative arteriograms and to correlate this observation with the results of oculopneumoplethysmography (OPG) and severity of carotid stenosis as determined by duplex ultrasonography and angiography. PATIENTS AND METHODS: Ninety-five patients underwent OPG, duplex ultrasonography, and selective carotid and vertebral arteriography. RESULTS: In all, 45 (88%) patients with a positive OPG had interhemispheric cross-filling of the middle cerebral artery and anterior cerebral artery from a contralateral carotid injection in contrast with 10 (23%) patients with a negative OPG (P < 0.001). Of patients with carotid stenosis > or = 80% on duplex ultrasound, 39 (91%) had cross-filling from a contralateral carotid injection in contrast with 16 (31%) patients with < 80% stenosis (P < 0.001). Of patients with carotid stenosis > or = 80% on arteriogram, 37 (90%) had cross-filling from a contralateral carotid injection in contrast with 18 (33%) patients with < 80% stenosis (P < 0.001). CONCLUSION: These data suggest that the Circle of Willis is frequently incompetent as a collateral pathway and that arteriographic cross-filling is not a reliable index of this pathway. Patients with a positive OPG and corresponding carotid stenosis are likely to have a physiologically incompetent collateral pathway. Perhaps these patients should undergo surgery, even if the stenosis is less than 80%. PMID- 7879833 TI - Twenty-five years of gallbladder surgery in a small rural hospital. AB - BACKGROUND: During a 25-year period from 1967 to 1991, 1,058 gallbladder operations were done by one surgeon in solo practice in a rural 50-bed hospital. METHODS: Open cholecystectomy was performed on all but 6 patients who had cholecystostomy. Operative cholangiography was liberally used, and 19% of all patients required common duct exploration. The majority of the patients were older than 65 years of age and 19% were older than 75 years of age. RESULTS: The overall mortality was 0.7%. There were no deaths following cholecystectomy for chronic or acute nongangrenous cholecystitis, and all deaths occurred in patients older than 77 years of age. Most of the deaths occurred prior to 1978 and the last death was recorded in 1984. CONCLUSIONS: Rural America has a comparatively large proportion of the elderly population of our nation. Most of these patients prefer to have their surgery performed locally, provided the results are comparable with those of large neighboring medical centers. The results from this current series from a small rural hospital compare favorably with the published results from large medical and academic centers. PMID- 7879835 TI - The surgical implications of chronic granulomatous disease. AB - BACKGROUND: Chronic granulomatous disease (CGD) of childhood is a rare congenital abnormality of the phagocyte NADPH oxidase system. Affected neutrophils and macrophages have an ineffective respiratory burst and cannot destroy certain phagocytized bacteria and fungi. CGD patients usually present with recurrent pyogenic and fungal infections. Catalase-positive bacteria are frequently involved, since they metabolize the hydrogen peroxide they produce, making it unavailable for augmentation of microbicidal activity in CGD neutrophils. Afflicted patients also have a tendency to form granulomas, which can lead to obstruction of the gastrointestinal and genitourinary tracts. METHODS: Charts of 10 patients with CGD were reviewed for age at diagnosis, surgical procedures, complications of these procedures, and medical treatment. RESULTS: Eight of the 10 children were male. The average age at first presentation was 18 months (range 2 days to 9.8 years). Each child developed a mean of 9.9 infections and an average of 1.4 infections per year. All required surgical procedures, with an average of 2.9 procedures each. Five children had operative procedures for infections that preceded the diagnosis of CGD. The procedures performed most frequently were incision and drainage of soft-tissue abcesses (7) or perirectal abscess (3), thoracentesis (3), and bronchoscopy (3). Three children had poor wound healing following surgery. Two developed partial gastric outlet obstruction which resolved with antibiotic therapy. One developed granulomatous cystitis with obstruction which responded to antibiotics. CONCLUSIONS: Since patients with undiagnosed CGD may present with surgical problems, surgeons need to be familiar with this condition. The diagnosis should be suspected in children who have recurrent or unusual infections or unexplained problems with wound healing. PMID- 7879834 TI - Prognostic factors in adenocarcinoma of the cardia. AB - BACKGROUND: The optimal extent of resection for adenocarcinomas of the gastroesophageal junction is controversial. This study was conducted to examine whether the extent of resection is an independent prognostic factor in cardia cancer. METHODS: The records and survival data of 125 patients who underwent resection for cancer of the cardia were retrospectively analyzed. Multiple regression was used to evaluate prognostic factors in patients who underwent proximal gastric resection (PR) or total gastrectomy (TG) for cancer of the cardia. RESULTS: Seventy-five patients underwent PR and 50 TG. The 5-year survival was 40% for tumors confined to the esophageal wall (T1, T2), and 13% in more advanced cases (T1, T2; P = 0.0001). Twenty-two percent of the patients with tumor-free margins, 10% of those with microscopic residual tumor, and none with macroscopic residual tumor survived longer than 5 years (P = 0.0001 for any residual tumor versus no residual tumor). Lymph node involvement (P = 0.002) and stage (P = 0.0001) were also significant in the univariate analysis. Five-year survival was 18% after TG, and 17% after PR (P = NS). CONCLUSION: Multiple regression identified residual tumor and penetration depth as independent predictors of survival (P = 0.0002, and P = 0.0001, respectively). After correction for these factors, none of the following variables were of additional significance: extent of resection (TG versus PR), lymph node involvement, age, or Lauren's classification. In 19 of 20 cases with microscopic incomplete resection, it was the oral margin that was positive. We conclude that the extent of resection (TG versus PR) does not influence survival in adenocarcinoma of the gastroesophageal junction. PMID- 7879836 TI - A modest proposal regarding the orphan child of academic surgery--teaching. PMID- 7879837 TI - The relationship between career satisfaction and fellowship training in academic surgeons. AB - BACKGROUND: Academic surgeons make various important decisions about their careers; however, little is known about the relationships between fellowship training, career development issues, and academic responsibilities. METHODS: Surgeon members of the Association for Surgical Education were surveyed about career development issues. Three hundred ninety-two (75.2%) surgeons responded. RESULTS: An exploratory factor analysis of the career development issues revealed four career development factors. Statistically significant differences were found between types of fellowship training and the career development factors. Nonfellowship-trained and clinical-fellowship-trained surgeons spend their time similarly to physicians in other specialties. Research-fellowship-trained surgeons spent significantly more time doing research, had fewer concerns about professional confidence, and expressed greater satisfaction with their careers. CONCLUSION: There is a relationship between career development issues, fellowship training, and type of fellowship training. Attention to these issues may be important in recruiting and retaining academic surgeons. PMID- 7879838 TI - Problems with the fourth-year curriculum of students entering surgical residencies. AB - BACKGROUND: Because of concerns about the relevance of the fourth-year curriculum of students entering surgical residencies, this study was undertaken to analyze the curriculum, electives, and grades and to compare the students' elective choices with previously documented preferences of surgical educators. METHODS: Computer profiles of all fourth-year students at New York Medical College who entered surgical residencies during a 3-year period were reviewed. The records of 115 students (92 male, 23 female), who were placed in 68 categorical and 47 preliminary positions, comprised the study. Four-week rotations in internal medicine, neurology, and ambulatory medicine were mandatory. An average of 5.1 electives per student, along with time for vacation and interviews, filled the remainder of the year. RESULTS: Students were statistically significantly more likely to receive honors grades in electives. Students, especially those in preliminary positions, frequently selected electives in their eventual specialty choice. CONCLUSIONS: Program directors interviewing prospective candidates for residency should view elective grades with care. Students often take electives that duplicate or do not enhance their career choices. Elective grades are inflated and may be based on subjective evaluations. This issue should be investigated further, and the major surgical education organizations should propose meaningful changes. PMID- 7879839 TI - Is there value in audition extramurals? AB - BACKGROUND: It has become common for fourth-year medical students interested in surgical careers to leave their parent university to take extramural elective rotations in surgery at other institutions. These "audition extramurals," while of some educational value, are often repetitions of prior clerkships and may not broaden the student's educational horizons. Instead, they are intended to enhance a student's competitiveness in the match. While recent opinions and questionnaires have suggested that such extramural rotations are not valuable in general surgery, no study has formally evaluated the effect of extramural electives on the residency match. METHODS: Over a 6-year period, the authors reviewed the outcome in 99 students who took extramural elective rotations in surgery. Of the 99 students, 28 were from the authors' institution who left to do extramural rotations elsewhere and 71 were outside students who came to the University of South Florida for an elective. While the elective rotation increased the probability of an interview, it did not alter ranking or probability of matching. RESULTS: For general surgery students, the elective rotation may actually decrease competitiveness, while for specialty students, it appears necessary but not sufficient to improve match outcome. The elective might facilitate placement for students who did not match, but did not do so predictably. CONCLUSIONS: The authors conclude that extramural elective rotations should be taken for educational value only and not as auditions for residency. PMID- 7879840 TI - Assessment of a surgical pattern recognition examination. AB - BACKGROUND: Recent cognitive research in medicine has demonstrated that expert diagnosticians solve many clinical problems through "pattern recognition" rather than deductive reasoning strategies. Development of the ability to recognize and diagnose common surgical problems is a critical objective of undergraduate surgical education. A surgical pattern recognition examination (PAT) was developed to assess surgical diagnosis recognition in clerkship students. METHODS: Surgical faculty selected 18 diagnoses for 20 possible presenting complaints (eg, leg pain, soft tissue mass). A distinctive patient description was written for each diagnosis. An examination of 200 items was compiled covering 20 presenting complaints. RESULTS: The PAT was administered to clerkship students during the 1992-1993 academic year (n = 77). PAT scores ranged from 33% to 90% with a mean of 65% (SD = 12.7). PAT scores correlated highly with the National Board of Medical Examiners (NBME) Surgery Subject Examination (SSE) scores. The validity of the examination was assessed by a speeded administration of the exam to surgical house staff. Senior residents scored significantly higher than junior residents (mean 82% versus 63%, P = 0.004). Performance on the PAT was significantly affected by the order of the student rotation in the academic year (P = 0.02) while performance on the NBME SSE was not (P = 0.40), which is consistent with diagnostic ability improving with clinical experience. CONCLUSIONS: The surgical PAT examination is a new, reliable, and valid method for assessing diagnostic ability in third-year students. PMID- 7879841 TI - Intraoperative cholangiography is not essential to avoid duct injuries during laparoscopic cholecystectomy. AB - BACKGROUND: Whether or not to perform intraoperative cholangiography (IOC) with laparoscopic cholecystectomy is controversial. The decision to perform IOC should depend on the individual surgeon's preference for the management of choledocholithiasis. PATIENTS AND METHODS: An initial experience of 525 patients undergoing laparoscopic cholecystectomy done without IOC is reviewed. RESULTS: Suspected or proven choledocholithiasis was managed by endoscopic retrograde cholangiography with sphincterotomy if necessary. There were no bile duct injuries or bile leaks, and 9% (47) of patients underwent endoscopic investigation or treatment. There have been no secondary operations for duct stones. CONCLUSION: We think that the use of IOC to avoid bile duct injuries is not essential, and that the key to avoiding such injuries is meticulous demonstration of anatomic detail at operation. We have been satisfied with selective use of endoscopic cholangiography and sphincterotomy for the management of choledocholithiasis. PMID- 7879842 TI - Access to the superior mediastinum. AB - Surgical access for diseases that involve the superior mediastinum can be achieved without thoracotomy by utilizing the suprasternal approach with extension of the head and neck and transection of the interclavicular ligament, median sternotomy, resection of the medial third to one half of the clavicle, or resection of the manubrium sterni. There has been minimal morbidity and no operative or postoperative mortality in a review of 53 consecutive patients. There has been no significant disability. Combined with exposure at the base of the neck, the access to the superior mediastinum is good to excellent. PMID- 7879843 TI - The antiobstruction stitch in stapled Roux-en-Y enteroenterostomy. AB - During the past 9 years, 393 Roux-en-Y gastric bypass operations for morbid obesity were performed by one surgeon at a university hospital. Twelve of the 393 patients subsequently developed mechanical small-bowel obstruction, and 7 of these 12 cases developed in the initial 38 patients in this series. There were 2 cases of small-bowel volvulus and 10 cases of postoperative adhesions. Three cases of adhesive obstruction occurred at the jejunojejunostomy. Two of the patients with anastomotic obstruction required operative treatment, whereas the remaining patient was successfully treated by nasogastric tube decompression. A simple technique is described that has successfully prevented this type of anastomotic obstruction in 355 subsequent Roux-en-Y gastric bypass operations. This technique should be useful in preventing anastomotic obstruction after any stapled end-to-side enteroenterostomy. PMID- 7879844 TI - Long-term outcome of surgery for thoracic outlet syndrome. AB - BACKGROUND: Thoracic outlet syndrome (TOS) is one of the most controversial symptom complexes in surgery today. Even the existence of TOS is questioned and where it seems to exist, the incidence varies from one country to another. Surgery is often considered the primary treatment; however, the frequency of good results after surgery varies from 24% to 100%, and in recent years the surgical approach has been questioned. PATIENTS AND METHODS: In this study 45 patients who had undergone surgery for TOS symptoms over a period of 21 years were examined by an independent clinician an average of 8 years after the operation. RESULTS: Forty-three percent of the performed operations were found to have been successful. Preoperative nocturnal and neck pain were more frequent in the unsuccessful group; no other preoperative characteristics had a predictive value. Preoperative radiographic and neurophysiologic examinations were also not predictive of the outcome. CONCLUSION: It is recommended that the feasibility of conservative therapeutic approaches should be evaluated before undertaking surgery for TOS symptoms. PMID- 7879845 TI - The role of gastric surgery in the multidisciplinary management of severe obesity. AB - Severe obesity affects the health and quality of life of 4 million Americans. The major cost of treating severe obesity and its associated comorbidities of hypertension, diabetes, cardiovascular disease, pulmonary insufficiency, cancer, and degenerative arthritis as well as the poor long-term results of medical, drug, and behavioral therapy has increased the numbers of patients being referred for surgical treatment. Gastric bypass and vertical banded gastroplasty are the two procedures recommended for severely obese patients. These operations currently have low morbidity and mortality. Surgery should be considered adjuvant therapy and must be part of a multidisciplinary approach. The significant long term weight control resulting from the surgical therapy is associated with improvement and, often, resolution of comorbidities, including diabetes, hypertension, hyperlipidemia, and pulmonary insufficiency. PMID- 7879846 TI - The clinical and genetic manifestations of hereditary nonpolyposis colorectal carcinoma. AB - BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) is a syndrome that affects a significant percentage of the total cancer population but is not easily recognized because of a lack of a distinctive clinical marker such as multiple polyps. DATA SOURCES: The present review discusses the clinical characteristics, pathology, genetics, management, and surveillance of HNPCC. The diagnosis of HNPCC is dependent upon family history. It is defined by the Amsterdam criteria consisting of: (1) 3 or more relatives with histologically verified colorectal carcinoma, 1 of whom is a first-degree relative of the other 2; (2) colorectal carcinoma involving at least two generations; and (3) one or more colorectal carcinoma cases diagnosed at less than 50 years of age. CONCLUSIONS: The diagnosis of HNPCC requires the demonstration of vertical transmission of the syndrome in the family pedigree. Attention should be focused on reports of cancer of all anatomic sites and the determination of site, histology, and age at diagnosis. PMID- 7879847 TI - Arsenic contamination in groundwater in six districts of West Bengal, India: the biggest arsenic calamity in the world. PMID- 7879848 TI - Veterinary drugs: disposition, biotransformation and risk evaluation. AB - Veterinary drugs may only be produced, distributed and administered after being licensed. This implies that, prior to marketing, a critical evaluation of the pharmaceutical quality, the clinical efficacy and the over-all pharmacological and toxicological properties of the active substances will be performed by national and/or supranational authorities. However, despite a sophisticated legal (harmonized) framework, a number of factors involved in residue formation and safety assessment remain unpredictable or dependant on the current 'state of the art' in the understanding of molecular pharmacology and toxicology. For example, drug disposition and residue formation in the target animal species may be influenced by a broad variety of physiological parameters including age, sex and diet, as well as by pathological conditions especially the acute phase response to infection. These factors affect both drug disposition and metabolite formation. Furthermore, current thinking in toxicological risk assessment is influenced by recent developments in molecular toxicology and thus by an increased but still incomplete understanding of the interaction of a toxic compound with the living organism. General recognized principles in the evaluation of potential toxicants are applied in the recommendation of withdrawal times and the establishment of maximum residue limits (MRL values). Apart from toxicological-based assessment, increasing awareness is directed to other than toxicological responses, especially the potential risk of effects of antimicrobial residues on human gastrointestinal microflora. Thus, the methodology of risk assessment is discussed in the context of the recently established legal framework within the European Union. PMID- 7879849 TI - Developments in residue assay and metabolism study of growth-promoters by mass spectrometric analysis. AB - The French national reference laboratory, for the control of growth-promoter residues, has developed routine methods of multiresidue analysis. These are mainly for the determination of beta-agonistic and steroid compounds. Apart from this regulatory activity, some research into growth-premotor metabolism and assay has also been carried out. This research concerns the method development of assay and metabolism studies of new compounds, including in vitro metabolism studies on cell (mainly hepatocytes) cultures, as well as studying the organic synthesis of new compounds and metabolites. Three examples of the different areas of research are presented here: the metabolism study of 4-chlorotestosterone in cattle; a methodological study on beta-agonists assay by mass spectrometry; and a residue study of beta-agonists in edible tissues. PMID- 7879850 TI - Preliminary study of the metabolism of 17 alpha-methyltestosterone in horses utilizing gas chromatography-mass spectrometric techniques. AB - Little is known about the metabolism of 17 alpha-alkyl anabolic steroids in horses. In this study, the metabolism of 17 alpha-methyltestosterone is investigated by oral administration of a (1 + 1) mixture of the steroid and its deuteriated analogue. Both compounds were synthesized from dehydroisoandrosterone (DHA), using a Grignard reaction followed by an Oppenauer oxidation. Post administration urine extracts were analysed by gas chromatography--mass spectrometry (GC-MS) using both electron impact (IE) and chemical ionization (CI). Interpretation of the data was facilitated by observation of the fragment ions present in the mass spectra. Notably, the D-ring fragment ions were indicative of 15- or 16-hydroxylation, where 16-hydroxy metabolites showed ion pairs at m/z 218/221 and at m/z 231/234 while 15-hydroxy compounds gave the 231/234 ion pair alone. Unaltered D-rings showed fragment ions at m/z 143/146. The data showed that the main phase 1 metabolic processes were partial and complete reduction of the 3-oxo-4-ene group, 15-hydroxylation, 16-hydroxylation, 17-epimerization and hydroxylation at at least two other undetermined sites, postulated as the 6 and 11 positions. Phase 2 metabolism, in the form of glucuronide and sulfate formation, was also common. The information provided by this investigation will result in improved effectiveness of confirmatory analytical procedures for 17 alpha-alkyl anabolic steroids. PMID- 7879851 TI - Immunochemical detection of antibiotics and sulfonamides. AB - To control the maximum residue limits (MRLs) for residues of veterinary drugs in food of animal origin, according to EU regulations, a broad spectrum of sensitive analytical methods is required. One effective approach is the development of immunoassays, particularly for screening purposes. Strategies for the production of specific polyclonal and monoclonal antibodies against beta-lactams, tetracyclines, streptomycin, chloramphenicol, sulfonamides and trimethoprim, are outlined, as well as methods for the synthesis of the respective enzyme-labelled antigens. The sensitivity and the specificity of the antibodies were characterized, and the immunochemical test systems were designed as quantitative routine tests (microtitre plate format) and as rapid qualitative tests (membrane based assay formats). The detection limits of the assays were found to be well below the regulatory limits. The range of recovery, for the analysis of artificially contaminated samples, was between 68 and 104%. In principle, the enzyme immunoassays for antimicrobial drugs showed the advantage of sensitivity and speed together with the simplicity of manipulations involved in the procedure. However, because of the results of the specificity studies, as well as the possibility of false positive results owing to unspecific inhibition of the assay, confirmation of immunoassay results is still required for all legal and statutory purposes. PMID- 7879852 TI - Imidocarb depletion from cattle liver and mechanism of retention in isolated bovine hepatocytes. AB - Imizol injection (imidocarb) is used for the prevention and treatment of babesiosis in cattle. Studies in sheep indicate that imidocarb is retained in edible tissues (Aliu et al.). In the present study we have set up and validated a high-performance liquid chromatography based method to investigate the retention of imidocarb in cattle liver. Imidocarb was still detectable 224 d after a single therapeutic dose with a half-life of 42.7 d. The mechanism of imidocarb retention by bovine liver was modelled using isolated bovine hepatocytes. Incubations with isolated hepatocytes indicated that [14C]imidocarb binding was dependent on hepatocyte number and showed signs of saturation. Bound [14C]imidocarb could be eluted from hepatocytes with buffer and extracted with solvents. Equilibrium dialysis under denaturing conditions (Sun and Dent) indicated that 3% of the [14C]imidocarb was covalently bound to macromolecules. Although the hepatocyte preparations demonstrated the capacity for phase I and II 7-ethoxycoumarin metabolism no metabolites of [14C]imidocarb were found. Further in vitro binding studies involving sub-cellular fractionation indicated that [14C]imidocarb is partitioned largely in the nuclear fraction of bovine liver homogenates and that it binds to deoxyribonucleic acid. PMID- 7879853 TI - In vitro and in vivo studies of drug residue accumulation in pigmented tissues. AB - A procedure was developed to enable ready isolation of melanin granules from pigmented tissues of the bovine eye. The granules were used in a simple in vitro test to model the potential for a range of veterinary drugs to accumulate in melanin-containing tissues such as hair and the choroid/pigmented retinal epithelium (choroid/PRE) of the eye. The beta-agonists clenbuterol and salmeterol, but not salbutamol, showed appreciable binding, as did the beta blockers propranolol and carazolol and the tranquillizers azaperone and xylazine. All of the natural and synthetic growth promoters tested gave rise to significant binding (17 beta-estradiol, testosterone, alpha-zeranol, diethylstilbestrol and 19-nortestosterone) but progesterone and 17 alpha-trenbolone bound to a lesser extent. To provide a preliminary indication of the validity of the model, animals were treated with clenbuterol for 21 d, to enable the assessment of accumulation in vivo. Clenbuterol was detected in choroid/PRE and hair at high concentrations from the last day of treatment (1779 ng g-1 and 424 ng g-1, respectively) until the end of the study period, 63 d later (512 ng g-1 and 483 ng g-1, respectively). These studies clearly indicate the wider potential for pigmented tissue analysis in monitoring for the use of veterinary drugs (particularly unlicensed substances) in food producing animals. Hair analysis may offer particular advantages for on-farm monitoring and in providing historic information. PMID- 7879854 TI - Determination of dexamethasone in urine and faeces of treated cattle with negative chemical ionization-mass spectrometry. AB - For several years, the misuse of dexamethasone and its esters in livestock production has been clearly demonstrated. The first part of the present study deals with the elaboration of a sensitive and specific method for the determination of residues of dexamethasone in excreta at the ppb level. Sample preparation for urine and faeces, including high-performance liquid chromatography (HPLC) fractionation, was carried out. The detection was based on established methodology employing negative chemical ionization-mass spectrometry (NCI-MS) after oxidation of the dexamethasone. In comparison with previous literature, the yield of oxidized dexamethasone was substantially improved and the oxidation procedure was made more simple and robust. In the second part of the study, the relationship between the dose of dexamethasone administered and the levels of the drug in excreta was investigated using this method, as was the ratio between drug levels in urine and faeces. Treatment was carried out for 7 d with an oral dose of 50 mg d-1, the maximum levels found in urine and faeces were 980 and 744 ppb, respectively. While the elimination via faeces responded much slower at the start and the end of treatment, the final part of both excretion profiles were very similar and a level of 1 ppb was reached in both matrices 9 d after the end of treatment. Gas chromatography-mass spectrometry (GC-MS) results obtained for the urine samples were compared with those obtained with direct enzyme immunoassay. PMID- 7879855 TI - Investigation of dissociation enhanced lanthanide fluoroimmunoassay as an alternative screening test for veterinary drug residues. AB - Both the number of drugs used in veterinary medicine and the diversity of procedures employed to detect their residues are ever increasing. Many laboratories that carry out such testing have employed a variety of immunoassays to serve as rapid screening tests. Owing to the high sensitivity, good reproducibility and availability of multi-analyte assays dissociation enhanced time-resolved fluorescence immunoassay (dissociation enhanced lanthanide fluoroimmunoassay, DELFIA) kits have become a market leader in the human clinical field. No commercial DELFIA kits are presently available for veterinary drug analysis. A DELFIA method was developed for the quantitative analysis of residues of medroxyprogesterone (MP) in bovine bile. Commercially available DELFIA reagents were used in a microtitre assay format. Within- and between-assay sr values (relative standard deviation) were 4.2-9.9 and 5.1-8.5%, respectively. Detection limits were calculated (mean + 3 s of a known negative population) as being 0.52 and 4.91 micrograms l-1 for male and female animals, respectively. A second study was carried out to optimize the labelling of haptens with a range of lanthanide metals. Purification of the hapten-lanthanide conjugates produced was achieved using fast protein liquid chromatography. Sensitive standard curves were produced for nortestosterone and diethylstilbestrol (curve mid-points of 30 and 40 pg, respectively). By using two different lanthanide labels (Eu and Tb) the simultaneous measurement of these compounds in a single assay system was achieved. Use of a third lanthanide label (Sm) yielded a product of low signal intensity and sensitivity. PMID- 7879856 TI - By-products of steroid synthesis: a cause of interferences in thin-layer chromatography residue analysis. AB - Since the late 1980s all of the laboratories involved in high-performance thin layer chromatography (HPTLC) control of hormonal residues in kidney fat, have occasionally detect a green fluorescent spot with similar RF values and colour to those observed for methyltestosterone (MT). This spot (product) could lead to false positive results for MT and was thus named 'le faux methyl' (the false methyl) by a french speaking colleague. All of the samples with a false methyl spot also contained a relatively high concentration of progesterone. Differentiation of this product from methyltestosterone can be performed in three ways: firstly, extra HPTLC on reversed-phased plates, secondly, extra purification of the extract with HPLC prior to HPTLC and thirdly, gas chromatography--mass spectrometry. This interference was identified as 20 beta hydroxyprogesterone, a by-product of progesterone. The problem of the false methyl was not only linked with the TLC characteristics of MT but also to the progesterone used as standard. Some laboratories used an analytical-reagent grade standard and others used commercial progesterone powders as standards (e.g., obtained in crude form from pharmaceutical companies). The commercial-grade progesterones showed two spots in comparison with the analytical standard that showed just one spot. As the false methyl was observed not only in kidney fat and meat samples, but also in illegal hormone cocktails, it was concluded that we had detected a by-product of an illegally used 'natural progesterone'. PMID- 7879857 TI - Determination of tilmicosin in ovine milk using high-performance liquid chromatography. AB - Tilmicosin is a novel macrolide antibiotic with a wide range of therapeutic uses against gram positive (+ve) and gram negative (-ve) bacteria and mycoplasmae causing pneumonia and mastitis and can be used to treat these diseases in sheep. After its use there may be residues present in ovine milk that interfere with cheese making and processing of other milk products. It is important to monitor for the presence of tilmicosin in ovine milk and a method has been optimized and validated for its determination. Tilmicosin is extracted from milk into methanol. The methanol extract is acidified and non-polar co-extractives removed using hexane followed by carbon tetrachloride. The pH is adjusted to 9.0 and the tilmicosin partitioned into chloroform. The chloroform extract is evaporated to dryness and the residue resuspended in high-performance liquid chromatography (HPLC) mobile phase. Tilmicosin is determined using reversed-phase HPLC and ultraviolet (UV) detection at 280 nm. Recovery of tilmicosin from ovine milk fortified over the range 50 to 250 micrograms l-1 is in the range 84.3-104.8%, with a relative standard deviation ranging from 6.6 to 12.9%. The proposed procedure allows the determination of residues of tilmicosin in ovine milk at levels less that 50 micrograms l-1 and satisfies the quality criteria specified in European Commission Decision 93/526/EEC with the exception of reproducibility data from interlaboratory trials. PMID- 7879858 TI - Endogenic nortestosterone in cattle? AB - When residues of nortestosterone (NT) were found in the urine of cattle, racehorses or bodybuilders, exogenic administration was thought to be proven. In previous literature, no records were found of the endogenic presence of this molecule. In the horse-racing world, Houghton and Courthot found that NT is normally present in the urine of the stallion. Belgian and Dutch researchers found that NT is also present in the urine and edible parts of the intact boar. Vandenbroeck et al. (1991) suggested the endogenous presence of NT (in the beta form) in the pregnant cow. Meyer (1992) reported the presence of NT (in the alpha form) in relatively high amounts in the urine of the cow peri-partum and the neo natal calf. These observations may have important consequences for veterinary meat inspection in the EU. Therefore, in Belgium a large scale experiment was set up in co-operation with the EU Community Reference Laboratory (RIVM). In this paper the present state of the results in this area is presented. A large number of urine samples (> 50) of pregnant non-treated cows were collected and analysed by gas chromatography-mass spectrometry (GC-MS) in 4 different laboratories. Further samples (> 100) were taken, but only analysed in one laboratory. The results proved clearly that NT may indeed be detectable in the alpha form in the urine of pregnant cows, from at least 2 months, but most probably from 4-5 months before partus. PMID- 7879859 TI - Synovial fluid as a matrix of selection in the detection of beta-adrenergic agonist drugs in carcases and fresh meat. AB - Previous papers have supported the hypothesis that beta-agonist drugs could accumulate in those tissues with a high content of mucopolysaccharides. Based on our preliminary findings, between October and December 1993 we randomly sampled 534 samples of synovial fluids drawn from the knee joint of fresh carcasses. After a preliminary extraction able to break down the water domains of mucopolysaccharides and the interactions between the matrix and the drugs, samples were concentrated on diatomaceous earth and then screened on two different ELISA plates. We confirmed the structure of suspected fluids by GC-MS (HFBA derivatization), according to EC criteria. Of the 57 samples screened as positive (10.6% of the total), 51 (9.5%) were fully confirmed, while for six it was not possible to identify the drug. The results suggest that the analysis of synovial fluids is an adequate tool to monitor the misuse of beta-adrenergic drugs in animal production, especially when target organs such as liver and kidney are not available for sampling. PMID- 7879860 TI - Confirmatory assay for the simultaneous detection of five penicillins in muscle, kidney and milk using liquid chromatography-electrospray mass spectrometry. AB - A confirmatory assay using liquid chromatography-electrospray mass spectrometry (LC-EMS) is presented for the simultaneous determination of penicillins V and G along with oxacillin, cloxacillin and dicloxacillin in muscle, kidney and milk. Nafcillin is used as an internal standard. Samples are extracted using acetonitrile and cleaned up using liquid-liquid extraction into dichloromethane. The extracts are injected into a dedicated LC-EMS instrument and any penicillins present are detected using multiple single-ion monitoring. Three or four ions can be detected for each penicillin, meeting one of the recommended EU criteria for confirmatory residue analyses using low-resolution mass spectrometry. The detection limits are below the stipulated EU maximum residue limits for each of the penicillins. PMID- 7879861 TI - Origin of chlortetracycline in pig tissue. AB - Violative chlortetracycline (CTC) residues in excess of the maximum residue limit (MRL) have been identified in 0.9% of all pigs tested at slaughter in Northern Ireland. Three experiments were carried out to investigate the possible reasons. In Experiment 1, pigs were fed CTC at therapeutic levels (300 mg kg-1 head-1 d-1) for 7 days and were slaughtered at day 0, 2, 4, 6, 8 and 10 following CTC withdrawal. Muscle, liver and kidney cortex and medulla samples were analysed for CTC residues by using high-performance liquid chromatography (HPLC). In all tissues, residues were less than the MRL from day 2 onwards. Mean CTC concentrations in kidney cortex were greater than medulla concentrations (p < 0.05). In Experiment 2, feed spiked with a sub-therapeutic dose of CTC (40 mg kg 1) was fed to six pigs that were slaughtered after 4, 8 and 12 days of medication. Violative CTC residues were not detected. In Experiment 3, short term supra-therapeutic administration was examined. Eight pigs received 500 mg kg-1 CTC head-1 d-1 for 1 or 2 days and were killed in pairs, 24 and 48 h following the final medicated feed. Violative levels were detected in both groups after 24 h only. It is concluded that: firstly, recommended CTC withdrawal periods are sufficient to avoid violative carcass residues; secondly, violative residues do not arise from sub-therapeutic dosing but can arise from supra-therapeutic dosing which could occur with inadequately mixed feed; and thirdly, the difference in kidney cortex and medullary CTC concentrations is significant from a regulatory perspective. PMID- 7879863 TI - Determination of anabolic esters in oily formulations and plasma in husbandry using high-performance liquid chromatography and gas chromatography-mass selective detection. AB - Two different analytical methods are described for the analysis of anabolic steroid esters in oily formulations for veterinary use and animal plasma samples, respectively. For the determination of anabolic steroid esters in oily formulations (at mg kg-1 levels) a reversed-phase high-performance liquid chromatographic method with gradient elution is described. Gradient elution is performed owing to the relatively large variations in polarity of the investigated anabolic steroid esters. For the analysis of anabolic steroid esters in plasma (at ng ml-1 levels) two different strategies are applied. After solid phase extraction, the plasma samples are introduced into the high-performance liquid chromatography (HPLC) system where the obtained fractions are then analysed by using gas chromatography-mass selective detection (GC-MSD). An alternative method is direct analysis of plasma samples after solid-phase extraction by using GC-MSD without any further clean-up procedure. Prior to GC MSD the samples are derivatized to corresponding trifluoroacyl (TFA) derivatives. The calibration graph for HPLC is rectilinear over the range 25-150 ng ml-1 plasma and the analytical recoveries for medroxyprogesterone acetate (MPA) and testosterone propionate (TP) are more than 95%. The detection limits for both analytes in GC-MS are 2.5 ng ml-1 plasma for MPA and 0.5 ng ml-1 plasma for TP with an acceptable signal-to-noise ratio (calculated for the derivatized relative molecular mass). In the analysis of plasma obtained from animal experiments concentrations of 6.5 ng ml-1 are found for MPA by using GC-MSD and 5.0 ng ml-1 are found for nortestosterone laurate (NL) by using HPLC. PMID- 7879862 TI - Experimental administration of 19-nortestosterone and dexamethasone in cattle: elimination of the two drugs in different biological matrices. AB - 19-Nortestosterone (19-NT) is one of the mostly recurrent anabolic agents on the black market of illicit drugs. Dexamethasone (DEXA) is licensed for therapy in veterinary practice but its misuse, although often suspected, has seldom been demonstrated. The excretion of 19-NT and DEXA is well documented when the compounds are administered independently but poor information is available in literature for instances when both drugs are administered as a mixture. To evaluate a radioimmunoassay (RIA) for anabolic residues in urine, blood and faeces, the effect of the simultaneous administration and the subsequent elimination of the two drugs, two animals were injected (4 times) with 19-NT and another two (4 times) with 19-NT-DEXA. After preparation and a sequential clean up on C18 and alumina columns, the samples were analysed by means of a specific 19-NT radioimmunoassay kit and an anti-DEXA antibody. Detection limits for both drugs were 0.5 ppb in blood samples and 2.0 ppb in urine and faecal samples. After the final treatment, positive 19-NT results were recorded at 14 and 21 d in urine and faecal samples, respectively. In the same matrices, positive DEXA values were found at 11 and 28 d, respectively. In the same matrices, positive DEXA values were found at 11 and 28 d, respectively. Urinary excretion was the main metabolic path both for 19-NT and DEXA; only 30% of the residues were excreted via the faeces. The simultaneous injection of DEXA and 19-NT increased the urinary excretion of 19-NT; however, the excretion of 19-NT via faecal matter was similar for both groups. PMID- 7879864 TI - Analysis of [3H]estradiol-17beta metabolites in calf perirenal fat. AB - Residues of estradiol-17 beta (E2 beta) in the kidney fat of one milk-fed calf were studies using radiometric methodologies. A three-month old Friesian male veal calf was injected intramuscularly daily for 3 d with 333 mg of [6,7(n)-3H] E2 beta (specific activity: 7.55 MBq mmol-1) dissolved in 2 ml of propylene glycol and slaughtered 3 h after the last administration. Total estrogens were about 280 ng g-1 in perirenal fat. After a de-lipidation step, the relatively polar metabolites that were extractable with dichloromethane represented the main fraction of the metabolites, which accounts for almost 50% of the total radioactivity of the tissue, of which E2 beta was the major metabolite (19.7%) and E1 and E2 alpha represented only 7.7 and 3.2%, respectively. Conjugated estrogens accounted for only 15.2% of the total estrogen content. Non-polar estrogens (about 25% of total estrogens) were removed specifically with isooctane during the de-lipidation step and were further purified on silica and alumina columns before being chromatographed by normal-phase HPLC. The radioactive metabolites were eluted as estrogen-17 esters. The HPLC analysis of the estrogens released following hydrolysis of the esters indicated that E2 beta was the main estrogen acylated by long-chain fatty acids in the fraction of lipoidal estrogens. The presence of such a class of estrogens in fat could be of interest for the detection of estrogens a considerable time after estradiol administration. PMID- 7879865 TI - Method validation in relation to accuracy and precision for the gas chromatography-mass spectrometric analysis of 19-nortestosterone in urine with heptafluorobutyric anhydride and N-methyl-N-(trimethylsilyl)trifluoroacetamide. AB - Method validation for all the analytical methods used in food control is of the highest priority. For this control there is a lack of reference materials, thus, it is necessary to validate the methods each time they are used for new applications. Among the many aspects of validation, this report pays particular attention to repeatability and reproducibility. The within-assay variability gives a good indication of the precision of the method shown by the repeatability. The between-assay variability gives no indication on the accuracy (or trueness) because no certified reference material is available. The reproducibility however, also gives an indication of the precision of the method. In this work the limit of detection, also an aspect of validation, was found to be below 0.375 micrograms 1-1 for both derivatization methods; however, the precision of the heptafluorobutyric anhydride method was found to be better than that of the N-methyl-N-(trimethylsilyl)trifluoroacetamide method. PMID- 7879866 TI - Generic immunoassay of corticosteroids with minimum pre-treatment of urine samples. AB - A generic, rapid and sensitive enzyme linked immunosorbent assay (ELISA) test has been developed which allows large-scale simultaneous testing of synthetic corticosteroids viz., flumethasone, dexamethasone and betamethasone. This assay can be directly applied to diluted urine samples (1 + 9) without hydrolysis of glucuronide or sulfate conjugates or any other treatment of samples. The polyclonal antibody was obtained by immunizing sheep with a flumethasone derivative linked to human serum albumin. This polyclonal antibody displayed high reactivity with several synthetic corticosteroids whilst endogenous corticosteroids such as cortisol gave very low cross-reactivity (< 0.5%). Sensitivities obtained in this assay were 2.5, 3.1 and 12.5 ng ml-1 for flumethasone, dexamethasone and betamethasone, respectively. The ability of this assay to detect several synthetic corticosteroids was demonstrated by testing urine samples from horses to which the drugs had been administered. PMID- 7879867 TI - Control of the illegal administration of natural steroid hormones in the plasma of bulls and heifers. AB - In the context of the control of the illegal administration of natural steroid hormones in cattle husbandry, an attempt was made to establish the decision levels for sex steroid hormones in the plasma of adult cattle, taking into account the effect of the treatment. Bulls and heifers were treated with two injections, at a two week interval, of an estradiol-testosterone cocktail. Steroid hormone and biochemical precursor concentrations were measured in plasma samples by using specific radioimmunoassays, before and after the treatment. When the treatment significantly (p < 0.05) modified a hormone concentration, a decision level was established for that hormone concentration. At each decision level, a score was assigned that represented the percentage of treated animals detected when the decision limit was applied. For heifers, 17 beta-estradiol and testosterone concentrations in plasma, which increased after the treatment, are the best criteria to use to detect treated animals, with decision limits of 20 pg ml-1 and 125 pg ml-1, respectively. In the instance of bulls, both testosterone and steroid biochemical precursor concentrations decreased in the plasma after the treatment. We proposed decision limits of 1500 pg ml-1 and 28 pg ml-1 for testosterone and androstenedione concentrations, respectively, the bulls displaying concentrations below these limits being positive. We observed that the repetition of the injection increased the score of the decision limit. The scores for testosterone are 70%, 14d after the first injection and 100% 14 d after the second injection, and for androstenedione, these scores are 60 and 100%, respectively. PMID- 7879868 TI - Stability of zeranol, nandrolone and trenbolone in bovine urine. AB - The stability of some growth promoting agents in cattle urine, under various temperature storing conditions, was investigated. Bovine urine samples obtained from previous excretion studies which contained zeranol, nandrolone and trenbolone respectively, were stored frozen, at room temperature and in direct sunlight. On days 0, 2, 4, 7 and 10, zeranol and nandrolone were quantified by selective ion monitoring analysis on a gas chromatography-mass selective detector and trenbolone by using an enzyme linked immunosorbent assay. Zeranol and its metabolite taleranol are stable under all of these storage conditions. There is a remarkable decrease in the concentration of 17 alpha-19-nortestosterone, the main metabolite of nandrolone in cattle, when stored at room temperature and in direct sunlight. There is also a decrease in concentration of trenbolone when stored in direct sunlight. From the results it can be concluded that urine specimens obtained from cattle for residue analysis should be frozen as soon as possible after collection. PMID- 7879869 TI - Survey of the hormones used in cattle fattening based on the analysis of Belgian injection sites. AB - Although the illegal use of orally administered compounds in cattle fattening has gained popularity, injection sites are still frequently found during control experiments on the carcasses in the slaughterhouses. The high concentrations of hormones in injection sites enable screening for the presence of 39 different hormones by a simple extraction followed by a fast and simple high-performance thin-layer chromatography analysis. Analysis of injection-site tissue is particularly successful for determining the hormones that are illegally injected. This data can not be obtained by analysis of other biological matrices like faeces, kidney fat or urine, owing to metabolization and selective excretion and/or deposition of these compounds. Since 1989, over 2000 injection sites have been analysed in our laboratory, which yielded a good survey of the hormones that were illegally injected. Over this period, the natural hormones estradiol and testosterone (mostly present as their esters) have obviously been used extensively. It is clear that since 1990 clostebol acetate has remained the most abused exogenous hormone. Additionally, some distinct trends were noticed, e.g., a tendency towards a highly decreased use of nandrolone, an increased use of progesterone and an increased occurrence of certain androgens like stanozolol and fluoxymesterone. PMID- 7879870 TI - Combined immunoextraction approach coupled to a chemiluminescence enzyme immunoassay for the determination of trace levels of salbutamol and clenbuterol in tissue samples. AB - A monoclonal immunoglobulin G1 (IgG1) antisalbutamol, which exhibits a 75% cross reactivity with clenbuterol, has been used in the setup of an immunoaffinity chromatography method and a chemiluminescence enzyme immunoassay for the extraction and the quantification of salbutamol and clenbuterol in tissue samples. After analytical validation, the proposed methodology was applied to liver, kidney and muscle samples obtained from calves and pigs treated with these beta 2-agonists (100 micrograms per kg of body weight) for 10 d. This methodology allowed the quantification of both drugs until 6 d after the final dose. At this time, however, salbutamol and clenbuterol were concentrated in the liver. Our results indicate that the liver is the preferred tissue to sample for the detection of illegal use of beta 2-agonists as growth promoters, in the absence of urine samples. PMID- 7879871 TI - Detection of clenbuterol residues in hair. AB - Sixty rats were grown in the presence of 10 (n = 30) and 100 (n = 30) micrograms kg-1 body mass of clenbuterol for a period of 10 d. An immunoextraction step coupled with a competitive enzyme immunoassay allowed the quantification of clenbuterol in hair upon 20 (10 micrograms kg-1) and 30 d (10 micrograms kg-1) after the last dose. This accumulation in hair contrasts with the rapid clearance in tissues. The nature of the immunoreactive material was confirmed by mass spectrometry. PMID- 7879872 TI - Screening of cattle urine samples for the presence of beta-agonists with a functional test: some preliminary results. AB - A new procedure based on the measurement of biological effects has been developed for the determination of residues of beta-agonists, such as clenbuterol, in urine. A multi-chamber superfusion apparatus containing isolated trachea strips from guinea pigs was used to detect smooth muscle relaxation induced via beta 2 adrenoceptor activation. The trachea tissue was pre-contracted with metacholine. Urine samples were extracted using a solid-phase column containing reversed-phase and anion-exchange materials. Extracts were introduced into the superfusion apparatus via flow injection. The intensity and response of relaxation are dependent on the type and concentration of the beta-agonist introduced. The sensitivity of the assay for clenbuterol in calf urine is about 1 microgram l-1. This methodology in the present form is especially suitable for survey screening analysis for several types of samples. An extensive validation of the procedure is performed to determine the range of analytes that can be detected, the possibilities of analysing urine samples obtained from mature cattle or other animal species and the influence of cross-reacting substances. PMID- 7879873 TI - Multi-residue analysis for beta-agonists in urine and liver samples using mixed phase columns with determination by radioimmunoassay. AB - A method is described for the extraction of four beta-agonists, clenbuterol, salbutamol, mabuterol and terbutaline from bovine urine and liver samples using radioimmunoassay (RIA) as the method of determination. Following enzymic digestion of the liver samples using protease enzyme, the digest is centrifuged and the harvested supernatant is saturated with sodium chloride and adjusted to pH 11.0. An ethyl acetate-propan-2-ol mixture is used to extract the beta agonists from the liver digest. The samples of urine and liver extracts are adjusted to pH 6.0 and applied to mixed phase (XtrackT) columns. The column is washed with water and methanol and the beta-agonists are eluted with methanol containing 2% ammonia. After evaporation of the eluting solvent and reconstitution in ethanol the beta-agonist residues are determined by RIA, with standard graphs prepared in residue-free sample extract. The procedure has been validated for clenbuterol, salbutamol, mabuterol and terbutaline. The mean recovery of the beta-agonists from urine and liver is > 75% and > 85%, respectively. The detection limit is 0.13 ng ml-1 and 0.46 ng g-1 of clenbuterol in urine and liver, respectively. The high recoveries attained for both types of beta-agonists are a result of an efficient liquid-liquid extraction step coupled with a selective mixed solid-phase extraction procedure. PMID- 7879874 TI - Determination of fenoterol and ractopamine in urine by enzyme immunoassay. AB - Fenoterol and ractopamine are phenethanolamines with beta-adrenergic agonist activity. An enzyme immunoassay (EIA) for these compounds was developed using antibodies raised in a New Zealand white rabbit against fenoterol-bovine serum albumin and fenoterol coupled to horseradish peroxidase (HRP). The calibration graphs of fenoterol and ractopamine showed linearity over the concentration ranges 0.1-5 and 0.2-25 ng ml-1, respectively. Isoxsuprine showed a cross reactivity of 0.7% while the cross-reactivity of other beta-agonists was < 0.1%. The screening assay was used to detect fenoterol in urine samples obtained from an animal experiment in which male calves were treated with fenoterol (100 micrograms of fenoterol per kg of bodymass per meal for a period of four weeks). Using a direct method, without sample preparation, fenoterol concentrations ranged from 22 to 210 ng ml-1. The mean concentration of fenoterol after extraction in isobutanol was 3.5 times lower compared with the direct method. On applying enzymic hydrolysis in combination with isobutanol extraction, the mean concentration was eight times higher than that obtained when using extraction only. Gas chromatography-mass spectrometry (GC-MS) analysis confirmed the presence of fenoterol in most of these samples. However, probably owing to the absence of a proper GC-MS internal standard, the correlation between GC-MS and EIA concentrations was low (r = 0.7976). In general, the concentrations found by the EIA are much higher than those found by GC-MS, which might be caused by the presence of metabolites detected with the EIA. Fenoterol is excreted in urine mostly (about 85%) as glucuronidated-sulfated conjugate. The antibodies partly recognize the conjugated fenoterol, which makes it possible to use a direct screening assay. In blank calf urine the detection limits, mean background +3 times the standard deviation, are 1.3 (fenoterol) and 2.6 ng ml-1 (ractopamine). In bovine urine, however, owing to matrix effects, the detection limits are 20 times higher. PMID- 7879875 TI - Confirmational analysis of beta-agonists by cryotrapping gas chromatography Fourier transform infrared spectrometry. AB - Cryotrapping gas chromatography-Fourier transform infrared spectrometry has been used for confirmation analysis of the beta-agonists clenbuterol, salbutamol, mabuterol, bromobuterol, cimaterol, cimbuterol and mapenterol in urine and liver samples of veal calves, subsequent to selected ion detection gas chromatography mass spectrometry. Samples have been analysed as their trimethylsilyl and methylboronate derivatives. Methylboronate derivatives yielded strongly diminished chemical background and interference levels in the infrared chromatograms of standards and samples. The limit of identification for methylboronate derivatives was at the low ppb level in incurred samples. The similarity of analyte and reference spectra, together with the retention time, was found to be a useful criterion for confirmation of unknown compounds. PMID- 7879876 TI - Determination of amperozide residues in swine liver using liquid chromatography mass spectrometry. AB - Amperozide 4-[4,4-bis(4-fluorophenyl)butyl]-N-ethylpiperazine-1- carboxamide) is used in veterinary medicine because of its sedative effect on pigs. A method developed for the detection of amperozide residues in porcine liver using liquid chromatography with thermospray mass spectrometry (LC-MS) is described and compared with LC with electrochemical detection (LC-ED). For LC-ED analysis, the samples were extracted with acetonitrile and cleaned up on a Sep-Pak C18 cartridge. The residues of amperozide were separated on a C8 polymer-based reversed-phase column and determined by using amperometric detection at +1050 mV. For LC-MS analysis, the samples were extracted with ethanol and cleaned using liquid-liquid extraction. After separation on a C8 polymer-based reversed-phase column, the residues were detected by discharge-assisted ionization with positive ion detection MS using single-ion monitoring. The positive discharge ionization produced typical [M+H]+ molecular ions of amperozide (m/z 403) and the internal standard (m/z 431). The limit of quantification for both methods, determined by using spiked blank liver in the concentration range 20-100 micrograms kg-1, was found to be below 70 micrograms kg-1. PMID- 7879877 TI - Melanin as an adsorbent for drug residues. AB - The binding of seven veterinary drugs (clenbuterol, chlorpromazine, diethylstilbestrol, 19-nortestosterone, salbutamol, salicylic acid and trenbolone) to melanin from Sepia officinalis was investigated. Basic and hydrophobic drugs were the most strongly bound. Desorption by ethanol was complete for neutral drugs but only partial for the basic drugs, which suggests that binding of the latter involves an ionic component. A method of synthesizing melanin in an immobilized form (melanin-PS) on the surface of porous silica was developed. When the drug binding properties of melanin-PS were investigated, its capacity to bind the basic drug clenbuterol was found to be higher (5.9 nmol mg 1) than that for the neutral hydrophobic drug 19-nortestosterone (0.56 nmol mg 1); for both drugs the attainment of binding equilibrium with melanin-PS was relatively rapid (< 5 min). By virtue of its binding kinetics, high capacity and mechanical robustness, melanin-PS offers potential for use in chromatography or solid-phase extraction and may additionally enable modelling of drug-melanin interactions. PMID- 7879878 TI - Screening of non-steroidal anti-inflammatory drugs, barbiturates and methyl xanthines in equine urine by gas chromatography-mass spectrometry. AB - A gas chromatographic-mass spectrometric (GC-MS) screening procedure for 23 acidic drugs in equine urine is described. With the GC-MS method fifteen anti inflammatory drugs, five barbiturates and three methyl xanthines can be detected with good sensitivity and selectivity. The method consists of alkaline hydrolysis, extraction with organic solvent using salting-out, clean-up extraction, methylation and screening with GC-MS in selected-ion monitoring mode. The limit of detection is 10 micrograms 1(-1) or lower, for most drugs. PMID- 7879879 TI - Determination of succinonitrile in horse urine by gas chromatography-nitrogen phosphorus detector and gas chromatography-mass spectrometry. AB - A chromatographic method was developed to detect and confirm the presence of succinonitrile (SDN) in horse urine samples, for antidoping control. The urine samples (5 ml) were extracted with diethyl ether and screened by gas chromatography-nitrogen-phosphorus detector and the confirmation of the drug's presence was accomplished by using gas chromatography-mass selective detection. The recovery of extraction was 78 and 81% for 1.0 and 2.0 micrograms ml-1 (relative standard deviation, < 10%), respectively. Urine samples collected after the administration of Energisan were positive for SDN (1-30 h) in all samples analysed. PMID- 7879880 TI - Determination of xanthines by high-performance liquid chromatography and thin layer chromatography in horse urine after ingestion of Guarana powder. AB - The seeds of Guarana are rich in xanthines and are used for the preparation of guarana powder which is very commonly given to horses as a 'tonic' in Brazil. In this paper, the xanthine content of guarana powder was determined, in addition to its clearance time in horses. Thin-layer chromatography was used as a screening procedure and high-performance liquid chromatography was performed to quantify the drugs in both the powder and urine samples. The guarana powder was found to contain 2.16, 1.10 and 36.78 mg g-1 of theobromine (TB), theophylline (TP) and caffeine (CF), respectively, and in urine it was possible to detect TB and TP up to 13 d and CF up to 9 d after the administration of guarana powder. PMID- 7879881 TI - Enzyme immunoassay for the detection of levamisole in meat and milk. AB - Ovine polyclonal antisera were raised to aminolevamisole to develop an enzyme immunoassay for levamisole. The assay has been validated in milk and in 100 g l-1 muscle homogenate. The limit of detection is 1 microgram l-1. In milk the inter assay relative standard deviation (Sr) is 6% at 10 micrograms kg-1 and the intra assay Sr value 7.2%. In tissue homogenate the inter-assay Sr value is 12.7% at 5 micrograms kg-1 and the intra-assay Sr value is 3.8%. Total incubation time is 1 h. PMID- 7879882 TI - Sensitive spectrofluorimetric determination of tetracycline residues in bovine milk. AB - A novel, sensitive, high-performance liquid chromatographic method for the residue determination of tetracyclines in bovine milk has been developed. Clean up of the sample extracts is performed with metal chelate affinity chromatography. Detection is based upon the measurement of fluorescence induced by complexation of tetracyclines with the zirconium cation, which is added post column to the high-performance liquid chromatographic eluate. The method has been validated for oxytetracycline, tetracycline and chlortetracycline. Calibration curves using 'blank' milk fortified at the 10-200 ng ml-1 level showed good linear correlation. Accuracy was measured at the 100 ng ml-1 level and was found to be within acceptable limits using a t-test (alpha = 0.05). At this level both within- and between-day precision, as measured by relative standard deviation (S(r)), were less than 16% for oxytetracycline and chlortetracycline, and less than 20% for tetracycline. The most striking advantages of the proposed method, over previously reported methods, are the higher sensitivity and specificity achieved. Using a signal-to-noise ratio of 4:1, the detection limits of the assay were 1 ng ml-1 for oxytetracycline, 2 ng ml-1 for tetracycline and 4 ng ml-1 for chlortetracycline. PMID- 7879883 TI - Identification of tylosin in bovine muscle at the maximum residue limit level by liquid chromatography-mass spectrometry, using a particle beam interface. AB - A particle beam liquid chromatography-mass spectrometric method is presented as a confirmatory technique for analysis of tylosin residues in bovine muscle. After chloroform extraction and a diol solid-phase extraction clean-up, on-line liquid chromatography-mass spectrometry (LC-MS) of extracts is carried out on an RP-18 bonded silica column. The analyte is introduced into the ion source by a particle beam interface and identified by negative chemical ionization with selective ion monitoring. The tylosin molecular ion is obtained with this ionization mode. The response of the ion chromatogram peak areas is linear for the three levels of spiked muscle analysed (0.5, 1 and 2 maximum residue limit). Under these LC-MS conditions, other macrolide antibiotics such as spiramycin and erythromycin do not interfere with tylosin. PMID- 7879884 TI - Improved spectrophotometric assay for beta-lactam residues in kidney tissue. AB - This paper describes a detection system for beta-lactams using a commercially prepared carboxypeptidase enzyme (CPase) and a substrate system in which lactic acid is cleaved from a synthetic peptide, N alpha-N epsilon-diacetyl-L-lysyl-d alanyl-d-lactic acid. The lactate is itself oxidized by lactate dehydrogenase to form NADH. Oxidized NAD+ is regenerated by diaphorase with the simultaneous reduction of the colourless 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyl tetrazolium chloride hydrate (INT) indicator substrate to produce a red-mauve colour that is proportional to CPase activity. The presence of beta-lactams decreases the intensity of colour produced. The lower limit of detection for benzyl penicillin (Pen G) by this system is 20 ng g-1 compared with 50 ng g-1 by the same assay but using a R-d-ala-d-ala substrate from a commercial kit. PMID- 7879885 TI - Particle beam liquid chromatography-mass spectrometry method with negative ion chemical ionization for the confirmation of oxacillin, cloxacillin and dicloxacillin residues in bovine muscle. AB - To ensure human food safety, the European Union has defined maximum residue limits (MRLs) for veterinary drug residues in food products. Analytical methods need to be developed to confirm the presence of drugs at the MRL level. A method using particle beam liquid chromatography-mass spectrometry was developed for the confirmation of oxacillin, cloxacillin and dicloxacillin in bovine muscle at the maximum residue limit of 300 micrograms kg-1. Beta-lactams were extracted from tissues with ethyl acetate under slightly acidic conditions and separated on a C18 bonded silica column with a methanol-aqueous formic acid (2%) solution acetonitrile mobile phase. Negative ion chemical ionization with methane as the reagent gas was used to identify the compounds. The specificity required for a regulatory confirmation procedure was achieved by monitoring five fragment ions for each compound (selected ion monitoring mode): m/z 183, 198, 213, 214 and 241 for oxacillin; m/z 196, 248, 250, 275 and 277 for cloxacillin; m/z 165, 230, 232, 274 and 276 for dicloxacillin. PMID- 7879886 TI - Investigation of Charm Test II receptor assays for the detection of antimicrobial residues in suspect meat samples. AB - Charm Test II receptor assays for beta-lactams, sulfonamides, (dihydro)streptomycin and erythromycin were applied to 257 bovine muscle and kidney samples, and 215 porcine muscle and kidney samples collected from animals suspected to contain antimicrobial residues. The assays were run in conjunction with Agriculture and Agri-food Canada's routine diagnostic confirmation analyses for suspect samples collected at federally inspected packing plants. All samples were subjected to the Charm Test II receptor assays and thin layer chromatography bioautography (TLC-BA). Selected samples were quantitatively analysed using a liquid chromatographic method for penicillin G and a thin layer chromatography fluorescence densitometry (TLC-FD) method for sulfonamides. The Charm Test II assays for beta-lactams, (dihydro)streptomycin and erythromycin were an acceptable alternative to the TLC-BA screen for laboratory confirmation of the presence of these compounds, with enhanced sensitivity for (dihydro)streptomycin and erythromycin. In addition, the Charm Test II provided a sensitive screen for sulfonamides as confirmed by the standard TLC-FD procedure. The analysis time, laboratory space and analyst time required to complete the Charm Test II assays is less than that for TLC-BA. Operating costs are similar for both analyses, but the Charm Test II does require capital expenditure for a scintillation counter. PMID- 7879887 TI - Determination of josamycin residues in porcine tissues using high-performance liquid chromatography with pre-column derivatization and spectrofluorimetric detection. AB - A simple, selective and sensitive high-performance liquid chromatographic (HPLC) method has been developed for the measurement of josamycin residues in four porcine tissues (i.e., muscle, liver, kidney and fat). The sample preparation consisted of a homogenization step in an acetonitrile-10 mmol l-1 phosphate buffer mixture, pH 6.0 (35 + 65), centrifugation and a liquid-liquid extractive clean-up of the resulting supernatant with isooctane. Pre-column derivatization of josamycin was performed using cyclohexa-1,3-dione in ammonium acetate buffer, pH 5.0 (90 degrees C for 2 h). The derivative was chromatographed in an isocratic reversed-phase HPLC system. A LiChrospher RP 18 end-capped (5 microns) column was eluted with an acetonitrile-methanol-10 mmol l-1 phosphate buffer mixture, pH 6.0 (45 + 5 + 50). The capacity factor of the josamycin derivative was 17.5. Detection was achieved using spectrofluorimetry (lambda ex = 375 nm; lambda em = 450 nm). The structure of the derivative was assessed by using mass spectrometry. Full selectivity was obtained in the HPLC system versus other macrolide antibiotics (tylosin, spiramycin and erythromycin), aldehydes (formaldehyde, acetaldehyde and benzaldehyde) and endogenous compounds. Linearity and repeatability were tested. Correlation coefficients, for calibration curves in the range of 0.1-3.2 micrograms g-1, were greater than 0.999 for all tissues and the relative standard deviation (S(r)) was 4.9% (1.6 micrograms g-1; n = 6); recovery was higher than 88%. PMID- 7879889 TI - Confirmation of sulfonamide residues in kidney tissue by liquid chromatography mass spectrometry. AB - The development of a method to confirm the presence of sulfonamide residues in kidney tissues at levels at or above the maximum residue limit (MRL, 100 ng g-1 total sulfonamide) using a tandem mass spectrometer [i.e., mass spectrometry-mass spectrometry (MS-MS)] interfaced to a high-performance liquid chromatography is described. Although sulfonamides can be determined using a single quadrupole mass spectrometer with pseudo-MS-MS, advantages in interfacing to a tandem mass spectrometer are demonstrated. PMID- 7879888 TI - High-performance liquid chromatographic determination of oxytetracycline in channel catfish (Ictalurus punctatus) muscle tissue. AB - A high-performance liquid chromatographic method for the determination of oxytetracycline in channel catfish muscle tissue is presented. Oxytetracycline is extracted three times from muscle tissue with an ethylenediaminetetraacetic acid disodium salt-McIlvaine buffer (pH 4.0) by using an Ultra Turrax. Analysis is carried out by using high-performance liquid chromatography and an acetonitrile oxalic acid (0.05 mol 1(-1), pH 2.2) mixture (14 + 86, v/v) is used as mobile phase. Oxytetracycline is separated on a Lichrosorb RP-8 125 x 4.0 mm i.d. column and ultraviolet detection at 355 nm is used. The limit of quantification is 10 ng g-1 and the linearity, tested in the spiking range 20-500 ng g-1, is 0.9997. Recovery from muscle spiked at 20, 50, 100, 200 and 500 ng g-1 levels is in the range 70-80%. Precision, expressed as percentage relative standard deviation, is below 7%. The method is applied to muscle tissue from channel catfish fed on a medicated diet. PMID- 7879890 TI - Effect of temperature and diet composition on residue depletion of oxytetracycline in cultured channel catfish. AB - Oxytetracycline is an antibacterial agent widely used in fish farming. The normal method of administration of oxytetracycline to the fish is to mix the drug into the feed. As a consequence, the concentration of the drug in feed, together with the preparation and the composition of feed, can influence the disposition of the drug itself. An experimental study was carried out to evaluate the residue depletion of oxytetracycline from muscle tissue of channel catfish (Ictalurus punctatus) fed different medicated diets. Three hundred channel catfish were randomly divided into six tanks (50 fish per tank), maintained at water temperatures of 18 degrees C (three tanks) and 23 degrees C (three tanks). The animals were fed with three diets, differing in their energy content and composition, for the duration of the experiment oxytetracycline was added to the diets at a level of 7500 mg kg-1 for 7 d. After cessation of the treatment, five fish from each tank were killed on days 1, 3, 8, 13, 18, 24, 30, 35 and 40. Oxytetracycline residues in muscle tissue were determined by high-performance liquid chromatography. The results indicate that the energy level and chemical composition of the medicated diets administered to channel catfish influence oxytetracycline disposition in fish, and that temperature is an important factor in conditioning the reported dietary effects. Therefore, formulation of specific diets to administer drugs to farmed fish could assure better bioavailability of the chemotherapeutant and shorter withdrawal times. PMID- 7879891 TI - Novel approach to the 'on-site' testing for sulfamethazine in pork carcasses. AB - Rapid 'on-site' methods are required by the pork industry to screen for the presence of antibiotic residues in meat and meat products. There are few rapid and easy-to-use methods suitable for application in non-analytical laboratories. This paper describes a novel approach for the screening of sulfamethazine in pork muscle using matrix solid phase dispersion, a microcolumn preconcentration step and thin-layer chromatographic detection. The characteristics of the method are reported allowing for the detection of residues at the maximum residue limit of 100 ppb. Results from the industrial evaluation of the complete method are also presented. PMID- 7879892 TI - Enzyme immunoassay for the detection of isoxazolyl penicillin antibiotics in milk. AB - Polyclonal antibodies were raised against isoxazolyl penicillins in rabbits after immunization with a cloxacillin-human serum albumin conjugate. The antisera were tested in direct and indirect competitive enzyme immunoassays (EIAs), using glucose oxidase or horseradish peroxidase conjugates of oxacillin, cloxacillin, or dicloxacillin, respectively, as the labelled antigen. The relative cross reactivities of each test system with oxacillin, cloxacillin, and dicloxacillin, determined from the amount of antibiotic required for 50% inhibition of labelled antigen binding, were dependent on the antibiotic used as the labelled antigen. Other beta-lactam antibiotics did not cross-react in these test systems. In a direct EIA using a cloxacillin-horseradish peroxidase conjugate, cloxacillin and dicloxacillin in milk were detected at levels of 10 and 30 ng ml-1; the average recoveries at these levels were 102 and 84%, respectively. PMID- 7879893 TI - Use of protein A as an immunological reagent and its application using flow injection. A review. PMID- 7879894 TI - Rapid ion-pair liquid chromatographic method for the determination of fenbendazole in cows' milk. AB - A simple and rapid methodology for the analysis of fenbendazole residues in cows' milk, at levels down to 3 ng ml-1, has been developed. Samples are extracted with acetonitrile and centrifuged. The supernatant is de-fatted with isooctane, and mixed with dichloromethane. The separated aqueous layer is discarded, while the bottom organic layer is washed with a phosphate buffer (pH 10) and evaporated to dryness. The residue is dissolved in the mobile phase and analysed by ion-pair reversed-phase liquid chromatography, using octanesulfonate as the ion-pair reagent. Over-all recovery was found to be 99.0%, linearity was excellent and precision data based on within- and between-day variation suggested an over-all variation of 2.0%. PMID- 7879895 TI - Determination of aflatoxin B1 in agricultural commodities by time-resolved fluoroimmunoassay and immunoenzymometric assay. AB - A time-resolved fluoroimmunoassay (TR-FIA) and an immunoenzymometric assay (IEMA) were applied for the measurement of aflatoxin B1 in soya seeds, dried figs and raisins. The extraction procedure was simple and no clean-up was found to be necessary. Limits of detection were 0.5 microgram kg-1 for TR-FIA (range of linearity of calibration graph 2.5-5 x 10(4) pg; inter-assay relative standard deviation Sr < 5%) and 0.2 microgram kg-1 for IEMA (linear range 1.0-5 x 10(3) pg; Sr < 11%). PMID- 7879896 TI - Perspectives: a vital biomechanical model of the endochondral ossification mechanism. AB - BACKGROUND: Mechanical usage effects could explain many features of endochondral ossification and related processes. Mineralization of growth plate cartilage could reduce its mechanical strains enough to make its resorption begin and to guide it in space. By removing most of its mineralized vertical septae, resorption could overload the remainder enough to increase woven bone formation on them and construct the primary spongiosa. After it finishes mineralizing, the primary spongiosa could become stiff enough to begin partial disuse in strain terms, so BMU-based remodeling would begin replacing it with lamellar bone. This would construct the secondary spongiosa. In transferring loads from the growth plate to the cortex, the central metaphyseal spongiosa becomes deloaded. This disuse would make remodeling remove it in the diaphyseal marrow space. METHODS: The slow growth of epiphyses and apophyses gives their spongiosas more time to adapt to their loads than the metaphyseal spongiosa beneath faster growing growth plates. Compared to metaphyseal trabeculae, this leads to fewer and thicker epiphyseal trabeculae that turn over more slowly and should persist for life because they carry loads for life. RESULTS: Rapid turnover of metaphyseal cortex in very young subjects could let it strain enough to form woven bone. Increased thickness and slower turnover of this cortex in older subjects could reduce its strains enough to make lamellar bone form there instead. This would compose this cortex mostly of woven bone in the very young and of lamellar bone in adults. CONCLUSIONS: This model assigns particular importance to the stiffness and strains of tissues (as distinguished from their strength and stresses), to the relative rates of some processes, and to responses of the skeleton's biologic mechanisms to a tissue's typical largest mechanical strains (as distinguished from their stresses). PMID- 7879897 TI - Perspectives: applications of a biomechanical model of the endochondral ossification mechanism. AB - A biomechanical model of endochondral ossification (Frost and Jee, 1994. Anat. Rec., 240:435-446) can help to explain: (1) some differences in fracture patterns in children and adults, (2) increased fractures during the human adolescent growth spurt, (3) localization of stress fractures and pseudofractures to cortical instead of trabecular bone, (4) increased bone mass in adult-acquired and childhood obesity, (5) subchondral bone densification and osteopenia in some arthroses, (6) why and where mammals lose spongiosa with aging, (7) why, as percents of the original bone stock, metaphyseal trabecular bone losses with aging usually exceed cortical bone losses, (8) why osteochondritis dissecans and aseptic necroses of bone localize in epiphyses instead of metaphyses, (9) some features of growth plate histology in rickets and the chondrodystrophies, (10) why spontaneous fractures in osteoporotic patients affect vertebral more than metaphyseal spongiosa, (11) why osteopenias develop in most chronic, debilitating diseases, and (12) why histomorphometric values can differ in iliac bone biopsies obtained by the "vertical" Jamshidi and "horizontal" Bordier-Meunier techniques. PMID- 7879898 TI - Reduced surface area in apoptotic rounding of human Chang liver cells from serum deprivation. AB - BACKGROUND: The early stages of apoptosis (programmed cell death) are said to be characterized by internucleosomal DNA fragmentation and "condensation of the cytoplasm" in which cells round up, detach, and increase in density. We studied the causation of apoptotic rounding. METHODS: Human Chang liver cells in normal monolayer culture were compared with apoptotic counterparts derived from serum growth factor deprivation. Cell-by-cell analysis using the Coulter EPICS PROFILE II flow cytometer studied 1) the cell cycle from propidium iodide-DNA bindings, 2) uptake of neutral red (NR) dye, a viable cell marker, and 3) cytosolic pH (pHi) modulations from 2',7'-bis(2-carboxyethyl)-5(and-6)-carboxyfluorescein (BCECF) fluorescence ratios with NH4Cl prepulsing and forward scatter bitmapping of cell surface area. Morphometric studies were done in the Quantimet 570 image analyser. Uptake of trypan blue, neutral red, and 2 million mol.wt fluoresceinated dextrans was studied by light microscopy. Cytological profiles were examined in light microscopy and transmission and scanning electron microscopy. RESULTS: Three days of serum growth factor deprivation caused confluent flat substrate-attached cells to retract and round up, tethering tenuously to the substrate via thin microvillus attachments only. Ninety percent of cell surface area was lost with this flat-to-round change. There was high trypan blue staining with total loss of proliferative potential, and the entire genome was just fragmented DNA making up the solitary Ao (apoptotic) peak in cell cycle profiles. However, these rounded apoptotic cells also internalized huge 2 million mol.wt dextran particles and impermeant neutral red which is an established viable cell marker. The rounded apoptotic cells had an intensely acidic (pH 5.6) cytosol and therefore a steep [H+]i/[H+]o gradient promoting proton extrusion. The pHi upshifted dynamically upon acidification, recovering and even exceeding resting level by a whole pH unit. Surface area reduction occurred concomitantly in real time with pHi upshifts in these apoptotic cells. Acidification and recovery in apoptotic cells also produced enhanced uptake of neutral red. Cytological profiles showed abundant large endocytic channels and endosomes in the rounded apoptotic cells. CONCLUSIONS: Gross surface area reduction with evidence of distinctive endocytic activity including uptake of huge 2 million mol.wt dextran particles suggested large channel endocytic internalization as a causal factor in apoptotic rounding, in common with rounding in M-phase and interphase cells with pHi upshifting where concomitant surface area reduction and uptake of impermeant particles were similarly demonstrable. The reduction in size of the cell envelope, together with consequential concentration pressures, could account for the observed rise in cell density and shrinkage in cell size. As a symptom of continual pHi upshifting, apoptotic rounding appears to be a recovery-associated response rather than a direct consequence of the disruptive forces causing its death. PMID- 7879899 TI - Connections between the various elements of the cis- and mid-compartments of the Golgi apparatus of early rat spermatids. AB - BACKGROUND: The exact structural relationships of the saccules, membranous tubules, and vesicles that compose the cis- and mid-compartments of the Golgi cortex of rat spermatids was investigated to determine the relationship of these elements to each other. METHODS: Tissues fixed with glutaraldehyde and buffered in sodium cacodylate were examined with the electron microscope. Electron micrographs, including stereopairs, were analyzed to determine the three dimensional organization of the Golgi elements. RESULTS: The deeper layer of the Golgi cortex was composed of stacks of saccules connected to each other either by saccules or membranous tubules. The peripheral region of the Golgi cortex, located between the cis-side of the stacks and a network of overlying ER cisternae contained numerous membranous tubules and vesicles of two class sizes: 50-100 nm vesicles and microvesicles 5-10 nm in diameter. The tubules formed tight networks, known as cis-elements or cis-Golgi networks (CGN), which were strictly parallel and next to the first or cis-saccule of the stack. The cis elements were continuous with more loosely arranged peripheral tubules which formed elaborate, intertwined and interconnected networks. These peripheral tubules closely approximated the overlying ER cisternae in areas often showing fuzz-coated finger-like projections. Occasionally such peripheral tubules were continuous with ER cisternae. The saccules forming the stacks were continuous with membranous tubules which not only connected saccules of adjacent stacks, but also saccules of the same stack. These tubules were also connected with the tight tubular networks forming the cis-elements and the broad networks formed by the peripheral membranous tubules. Vesicles (50-100 nm) and microvesicles (5-10 nm) frequently formed aggregates in the peripheral Golgi region next to areas of ER membrane free of fuzz-coated projections. The microvesicles, embedded in a denser cytoplasmic matrix, had a more or less distinct delimiting membrane suggestive of their disintegration in this juxta-ER location. The 50-100 nm vesicles that were seen at the periphery of the vesicular aggregates appeared to form mainly from the membranous tubules of the Golgi cortex. CONCLUSIONS: Thus the saccules and membranous tubules of the spermatid's Golgi cortex formed a single continuous membraneous system connected to ER cisternae. The vesicles, seemingly arising from the membranous tubules, appear to follow a retrograde pathway and undergo dissolution next to ER cisternae. PMID- 7879900 TI - Ultrastructure of melanocytes in the dark cell area of human vestibular organs: functional implications of gap junctions, isolated cilia, and annulate lamellae. AB - BACKGROUND: It is known that melanocytes exist in almost all parts of the inner ear, such as the cochlear duct, stria vascularis, Reissner's membrane, modiolus, vestibular organs in the region surrounding the cristae and maculae, semicircular canals, and pars rugosa of the endolymphatic sac. But there have been few studies using human materials, because of the difficulty of obtaining materials. We attempted to investigate the detailed ultrastructure of melanocytes in the vestibular organs of human inner ear. METHODS: Eight surgical specimens obtained from patients with vestibular schwannoma were studied by light microscopy and electron microscopy. RESULTS: Melanocytes were found in the subepithelial layer of the dark cell area. Melanocytes had round or spindle-shaped nuclei and clear cytoplasm with brown pigment granules. Besides melanocytes, there were melanophages, fibroblasts, and small blood vessels. Through electron microscopy we found melanocytes with round-shaped melanosomes in various stages of pigmentation, well-developed Golgi apparatus and endoplasmic reticulum in the cytoplasm, and many cytoplasmic processes. Gap junctions were occasionally found between the cytoplasmic processes. And there were pinocytotic vesicles just under the limiting membrane of melanocytes, and intermediate filaments were abundant in the cytoplasm. Isolated cilia of melanocytes, annulate lamellae, and fusiform banded structures in the connective tissue area around melanocytes were found. CONCLUSIONS: Melanocytes in human vestibular organs actively synthesize melanosomes. Frequent findings of isolated cilia and fusiform banded structures and the incidental existence of annulate lamellae may be an indicator of this metabolically activated state of melanocytes. Moreover, monitoring environmental changes by isolated cilia, melanocytes in the human inner ear could act not only as one cell but also as a group to achieve their physiological functions by means of information transmission through gap junctions. PMID- 7879901 TI - Differentiation of periodontal ligament fibroblasts into osteoblasts during socket healing after tooth extraction in the rat. AB - BACKGROUND: The entire socket after tooth extraction is filled with new bone formed by osteoblasts (Obs), but the origin of these Obs remains unknown. Thus, the proliferation and migration of paravascular and endosteal fibroblastic cells and periodontal ligament (PDL) fibroblasts (Fbs) and their differentiation into Obs during socket healing after extraction of the first maxillary molars of the rat were investigated. METHODS: The proliferative activity and migration of these cells in the sockets after tooth extraction were studied using radioautography and immunohistochemistry after injection of 3H-thymidine and 5-bromo-2' deoxyuridine (BrdU), respectively. Their morphological changes during differentiation was investigated by transmission electron microscopy. RESULTS: One day after tooth extraction, PDL Fbs were the major cell type in the PDL remnant of the socket. Proliferation was low (labeling index (LI) = approximately 2%) until 16 h after tooth extraction but dramatically increased to a maximum level 1 day postextraction (LI = 23%). Between 1 and 2 days, numerous PDL Fbs in the PDL remnant actively migrated into the coagulum and continued to proliferate. On the basis of the high proliferative activity and small number of cellular organelles responsible for procollagen synthesis, these cells appear immature. At 3 days, Fbs contained more cellular organelles and deposited more collagen fibers as they replaced the coagulum with dense connective tissue and the LI declined. At 4 and 5 days, some of the Fbs began to differentiate into Obs, and the proliferation of Fbs dramatically decreased to baseline values. The migration of PDL Fbs and their differentiation into Obs were investigated by labeling with 3H thymidine or BrdU 1 day after tooth extraction. Heavily labeled Fbs were observed in the PDL remnant at 1 day, in the coagulum at 2 days, and in the dense connective tissue at 3 days. Labeled Obs associated with new bone were seen 4 days after injection. Endosteal and paravascular Fbs also proliferated, but at a lower level and at later time periods than the PDL Fbs. Surprisingly, endosteal and paravascular Fbs contributed only a small population of Fbs to socket healing. CONCLUSIONS: These results indicate that PDL Fbs after tooth extraction actively proliferative, migrate into the coagulum, form dense connective tissue, and differentiate into Obs which form new bone during socket healing. PMID- 7879902 TI - Type and regional diversity in the distribution of myosin heavy chains in chicken intrafusal muscle fibers. AB - BACKGROUND: Chicken intrafusal fibers were classified on the basis of their myosin heavy chain (MHC) composition, which was compared to that of mammalian nuclear bag and nuclear chain types. METHODS: Immunoreactivities of intrafusal fibers from leg muscles of 8-week-old chickens were evaluated in serial cross sections after incubation with monoclonal antibodies against slow-twitch, slow tonic, or fast-twitch MHC and fast muscle C-protein. RESULTS: Four categories of slow intrafusal fiber could be distinguished on the basis of differential expression of slow-twitch and slow-tonic MHC. Segregation into types was most evident at the motor axon supplied pole, followed by the sensory region of the equator. Fiber types were least distinct at the juxtaequator where sensory and motor axons meet. Intrafusal fibers negative for slow myosins reacted with anti fast myosins. Fast fibers were best viewed as a single group without subdivisions. Immunostaining for fast muscle C-protein paralleled in large part reactivities for neonatal/fast MHC, indicating that proteins other than MHC are useful fiber type markers. CONCLUSIONS: Despite regional changes along the length of intrafusal fibers and some variation within fiber types, the concept of separate MHC-based fiber types was valid as long as typing of fibers was restricted to the proximal polar region. Comparisons of MHC profiles revealed similarities between chicken fast intrafusal fibers and mammalian nuclear chain fibers and between some chicken slow intrafusal fibers and mammalian nuclear bag fibers. PMID- 7879903 TI - Immunocytochemical detection of actin and 53 kDa polypeptide in the epididymal spermatozoa of rat and mouse. AB - BACKGROUND: Presence of immunocytochemically detectable actin in the rat and mouse sperm head has been enigmatic for years. In this study, we demonstrate actin in the perinuclear theca and show that the detection of actin epitopes in the rat and mouse epididymal spermatozoa can effectively be enhanced by pre extraction of sperm cells with SDS. METHODS: The study with one monoclonal and one polyclonal anti-actin antibody was carried out at conventional and confocal fluorescence and electron microscope level, and by immunoblotting of proteins isolated from the head and tail fractions. RESULTS: In the head of the control methanol-acetone fixed rat spermatozoa, the polyclonal antibody gave a stronger immunostaining in the postacrosomal area and in the perforatorium than the monoclonal antibody. In the mouse sperm head, the monoclonal antibody labeled the ventral edge of the postacrosomal area and slightly the perforatorium, whereas the polyclonal antibody stained the entire perinuclear space. In the SDS extracted spermatozoa, an intense postacrosomal and perforatorial labeling was obtained with both antibodies but, in particular in the rat spermatozoa, the middle lateral portion of the postacrosomal segment remained unlabeled. Sonication seemed to cause structural modifications which specifically impeded staining with the monoclonal antibody. Both antibodies detected actin in the basal plate and the monoclonal antibody in the neck. Amorphous matrix of the connecting piece showed immunogold labeling. In the tail, the monoclonal antibody recognized actin and a relatively basic 53 kDa polypeptide, whereas the polyclonal antibody reacted with several protein bands. SDS-soluble actin of the tail was addressed to the midpiece and the SDS-insoluble 53 kDa protein profoundly to the outer dense fibers of the principal piece. CONCLUSIONS: Intense labeling of actin in the SDS-extracted rat and mouse spermatozoa was presumably due to the generated demasking of actin epitopes embedded in the perinuclear cytoplasm. The results are important in confirming that actin in the rat and mouse sperm head is not lost during spermiogenesis but apparently contributes to the three-dimensional packing of the mature perinuclear cytoplasm. This study further demonstrates the importance of the methods used in sample preparation and advantages of confocal microscopy when attempting to detect cytoskeletal proteins which, as in spermatozoa, may occur in small quantities. PMID- 7879904 TI - Anatomical localization of immunoreactive oxytocin and beta-endorphin in the bovine neurointermediate lobe. AB - BACKGROUND: Beta-endorphin and oxytocin immunocytochemical localization were examined in the neurointermediate lobe (lobus nervosus and pars intermedia) of the bovine hypophysis in order to describe the anatomical distribution of these two neurointermediate lobe hormones. METHODS: Twenty-seven bovine hypophyses were collected from slaughterhouse animals (seven mature lactating cows, eleven mature nonlactating cows, three nulliparous heifers, and six steers). Hypophyses were immunostained for oxytocin-containing fibers and beta-endorphin-secreting cells by using the avidin biotin-immunoperoxidase method. The distributions of beta endorphin-positive cells and oxytocin-positive nerve fibers were plotted on projected outlines of the hypophyses. Immunoreactive staining intensity was graded numerically as weak, moderate, or heavy by three individuals who had no knowledge of the animals' physiological status. RESULTS: Oxytocin immunoreactivity was confined to the lobus nervosus while beta-endorphin staining was confined to the pars intermedia and the pars distalis. However, oxytocin immunopositive neurosecretory terminals were distributed more heavily in that part of the lobus nervosus bordering the pars intermedia than in the center of the lobe. CONCLUSIONS: These results were similar to those previously reported for the rat (Swaab et al., 1975; J. Neural Transm., 36:195-215; Deftos and Catherwood, 1980; Life Sci., 27:223-228). PMID- 7879905 TI - Ultrastructural localization of lectin receptors in the preimplantation ovine embryo. AB - BACKGROUND: Preimplantation development of mammalia is characterized by cell surface changes functioning in intercellular communication and adhesion. The glycoconjugate role in cellular interactions has been analysed for several groups but not in sheep embryos. The binding patterns of eleven lectins during sheep preimplantation development were investigated and the role of glycoconjugates in early development was discussed. METHODS: Ultrathin sections from preimplantation ovine embryos (3-7 days) were incubated with different colloidal gold conjugated lectins and the frequency of gold particles on the cell membrane, some organelles, and the zona pellucida was evaluated. RESULTS AND CONCLUSIONS: We observed a higher staining of WGA, DBA, and SBA lectins in the intercellular contact zone with respect to the free cell surface of blastomeres during cleavage. This indicates that the N-acetyl galactosamine and N-acetyl glucosamine residues may be involved in sheep morula compaction. In contrast, the trophoblast cell displays an increase of staining of some lectins previously identified during cleavage (LcH, WGA, SBA, MPA, and PNA) on the free membrane, and a lack of sugar residues in the intercellular surface. This polarization of the trophoblast cell surface is not observed in the inner cell mass and could provide a mechanism for differentiation within the blastocyst. Intracytoplasmic vesicles show a cytochemical identity with lysosomes in the blastocyst (abundant GlcNAc and Man/Glc residues) that may reflect a functional relationship between both organelles in an intracellular cycle. The zona pellucida presents abundant GalNAc, GlcNAc, and Gal residues during preimplantation ovine development. PMID- 7879906 TI - Maturation of undifferentiated lung epithelial cells into type II cells in vitro: a temporal process that parallels cell differentiation in vivo. AB - BACKGROUND: Formation of alveolar-like structures (ALS) by mature fetal rabbit type II pneumocytes (day 29 gestation) and long-term differentiation on Engelbreth-Holms-Swarm mouse tumor extract or EHS gel (Matrigel) were reported by our group (Blau et al., 1988. J. Cell Physiol., 136:203-214). We now describe structural organization and differentiation of immature lung epithelial cells, isolated at day 22 gestation, into mature type II cells in vitro. METHODS: Peripheral pulmonary tissue was pooled and undifferentiated epithelial cells isolated for primary culture on Matrigel. Cells were examined 12-16 h after plating and on days 1, 3, 5, and 7 of culture and assessed by phase contrast and by transmission electron microscopy after fixation in situ. RESULTS: Cells formed ALS 12-16 h after plating. Spherule diameter increased about four to eight times from day 1-7 in culture. There was rapid transformation of tall columnar cells to cuboidal, normal polarization of cells with respect to cell-free lumen of ALS, progressive reduction of glycogen zones, apparent gradual increase of cell organelles such as Golgi apparatus, rough endoplasmic reticulum and mitochondria, and apparent extrusion of lipidic figures into the lumen. These morphologic transformations in vitro temporally paralleled cell differentiation in vivo. The relative increase of 14C-acetate precursor into phosphatidylcholine in contrast to cardiolipin was consistent with these transformations. CONCLUSIONS: Under the conditions of our culture system, maturation of undifferentiated pulmonary epithelial cells is reproduced in vitro along the same time course and according to the same developmental sequence of fetal lungs in vivo. PMID- 7879907 TI - Formation of alternating tiers in the optic chiasm of the chick embryo. AB - BACKGROUND: When the fibers of the two optic nerves of the chick cross to the contralateral side at the prospective chiasmatic region, they segregate into clearly defined bundles. These bundles form horizontally oriented tiers which alternate between the right and the left optic nerve. METHODS: We have analyzed the development of these tiers qualitatively and quantitatively using light and electron microscopy between embryonic days (E) 4 and E19. RESULTS: The formation of the chiasm begins on E4. In the course of E4, tiers become visible for the first time. Their number increases rapidly until E7. Then the increase is slowed down and the final value (32 +/- 1) is approximated by E18/19. Growing axons allow one to distinguish three different segments: the growth cone, the distal, and the proximal segment. The latter originates in the perikaryon. Growth cones and distal segments are found predominantly in the ventralmost tiers. Their frequency decreases from ventral to dorsal. Proximal segments which indicate the presence of older axons appear first in the dorsal tiers and later also in more ventrally located tiers. CONCLUSION: Based on these criteria it is concluded that newly formed axons contribute primarily but not exclusively to the ventral tiers. There is a gradient of maturity of axons from ventral to dorsal whose slope becomes steeper with age until the last growth cones have arrived by E18. Thus, the formation of the chiasm corresponds to the spatiotemporal pattern of ganglion cell formation in the retina. The process of cell death of retinal ganglion cells is also seen in the chiasm but probably does not lead to a transitory diminution in the number of tiers. PMID- 7879908 TI - Hamster supraoptic nucleus: cytoarchitectural, morphometric, and three dimensional reconstruction. AB - BACKGROUND: The present paper describes the cytoarchitectonic, morphometric, and three-dimensional characteristics of the golden hamster supraoptic nucleus (SON) in order to provide an anatomical basis for subsequent morphofunctional studies that use this species as an experimental animal. The dimensions (volume and length) and the number of cells of each part of the supraoptic nucleus were obtained, as well as morphometric parameters of their neurons (cross-sectional area and maximum and minimum diameters). A three-dimensional reconstruction of hamster SON has been made in order to know the spatial morphology of this nucleus and to reveal the structural differences between both parts. METHODS: Ten male adult golden hamsters (Mesocricetus auratus) were used. Animals were anaesthetized and transcardially perfused with 4% paraformaldehyde in 0.1 M phosphate buffer at pH 7.2. The hypothalamic area from seven animals was dissected out, dehydrated, and embedded in paraffin. Serial sections of 10 microns were cut in a coronal plane. Sections were stained with thionin, dehydrated, cleared in eucalyptol, and mounted with Eukitt. To prove the neurosecretory nature to the SON, every fourth section was immunostained against neurophysin by using the peroxidase-antiperoxidase method. To study the neuronal morphometric parameters, all magnocellular neurons of the SON were drawn in sections separated 80 microns with the aid of a camera lucida under 500x magnification. Serial 50 microns thick frozen sections of the hypothalamus from three animals were drawn with camera lucida to determine the volume of the two parts of the SON and to make the three-dimensional reconstruction. RESULTS: The SON extends rostrocaudally 1.98 +/- 0.03 mm from the preoptic area to the tuberal hypothalamic area. Two classical parts can be clearly delimited: principal (SONp) and retrochiasmatic (SONr). The neuronal population of the two parts of the SON appears constituted only by magnocellular neurons. The volume of the SONp is 0.039 +/- 0.03 mm3 and contains about 762 +/- 93 magnocellular cells, with a density of 19,151.8 cells/mm3. The volume of the SONr is 0.126 +/- 0.03 mm3 and contains about 1,296 +/- 132 neurons with a density of 10,536.6 cells/mm3. The three-dimensional reconstruction reveals that the SONp appears located in a more cephalic, lateral, and dorsal position than the SONr, and a clear discontinuity between the two parts is observed. CONCLUSIONS: The present study shows that the classically termed SON, in the hamster, clearly consists of two spatially separated neural populations. The SONr is longer than SONp and has the larger volume and higher number of neurons; however, the neurons of the SONr are smaller in cell area than those of the SONp. PMID- 7879909 TI - Immunohistochemical localization of the high-affinity NGF receptor (gp140-trkA) in the adult human dorsal root and sympathetic ganglia and in the nerves and sensory corpuscles supplying digital skin. AB - BACKGROUND: Nerve growth factor (NGF) is produced in target tissues of sympathetic and neural-crest derived sensory neurons, including skin, to provide them trophic support. The biological effects of NGF on responsive cells are mediated by specific high-affinity receptors. Recently, a protein tyrosine kinase of congruent to 140 kDa molecular weight, encoded by the proto-oncogene trkA, has been identified as the high-affinity NGF receptor (gp140-trkA). The present work was undertaken to study the localization of gp140-trkA-like immunoreactivity (IR) in human peripheral ganglia (sympathetic and dorsal root ganglia), and in glabrous skin. METHODS: Lumbar dorsal root ganglia, para- and prevertebral sympathetic ganglia, and digital glabrous skin were studied immunohistochemically using a rabbit anti-gp140-trkA polyclonal antibody. In order to accurately establish the localization of gp140-trkA IR, the neurofilament proteins and S-100 protein were studied in parallel in: (1) sensory and sympathetic ganglia, to label neuron cell bodies and satellite or supporting cells, respectively; (2) human skin, to label axons, Schwann and related cells within nerves and sensory corpuscles. Moreover, a quantitative study (neuron size, intensity of immunostaining) was carried out on sympathetic and dorsal root ganglia neuron cell bodies. RESULTS: A specific gp140-trkA-like IR was found in: (1) a subpopulation (65%) of primary sensory neuron cell bodies, including most of the large-sized ones but also small- and intermediate-sized ones; (2) most of sympathetic neuron cell bodies (82%); (3) the perineurial cell, Schwann cells, and large axons of the nerve trunks supplying digital skin; (4) the lamellar cells of Meissner corpuscles; (5) the central axon, inner-core, outer-core, and capsule of Pacinian corpuscles. In addition, the occurrence of gp140-trkA-like IR was observed in some non-nervous tissues of the skin, including epidermis (mainly in the basal layer), sweat glands, and arterial blood vessels. CONCLUSIONS: Present results provide evidence for the localization of gp140-trkA-like IR in: (1) nerve cells which are known to be NGF-responsive, and (2) non-nervous cutaneous tissues which are innervated by NGF-dependent peripheral neurons. These findings suggest that, in addition to the well-established role of NGF on sensory and sympathetic neurons, this neurotrophin may be able to regulate some other functions on non-nervous cells which are targets for NGF-dependent peripheral neurons. PMID- 7879910 TI - Phagocytic defence mechanism in sea bass (Dicentrarchus labrax L.): an ultrastructural study. AB - BACKGROUND: The ultrastructure of the phagocytic process in fish has not been established in spite of the significant morphofunctional differences detected in the fish immune system with respect to the basic immunological pattern in vertebrates. We report the ultrastructure of the bacterial phagocytic defence mechanism in sea bass (Dicentrarchus labrax L.). METHODS: Head-kidney, blood, and peritoneal exudate leukocytes were challenged with Aeromonas salmonicida and Escherichia coli and processed for transmission electron microscopic study. RESULTS: Macrophages challenged with bacteria showed changes in the cell outline, in the chromatin pattern, and in the ultrastructural features of the cytoplasm as a consequence of an activation process. The phagocytic process consists of the following: 1) Bacteria-macrophage contact. One or more spot contacts between the bacterial wall and the phagocyte membrane are observed. 2) Bacteria engulfment. Slight depressions, membrane invaginations, or cytoplasmic processes are formed at the phagocyte surface. Macrophage processes occasionally surround the bacteria, overlapping and roaming parallel, or a single, long pseudopod encircles a bacterium several times. 3) Endocytic vesicle formation. Macrophages show one or more bacteria inside membrane-bound cytoplasmic vesicles. 4) Phagolysosome formation. Some dense granules (lysosomes) fuse with the endocytic vesicle. 5) Intracellular killing/digestion. Bacteria inside the endocytic vesicles are observed both virtually intact or damaged at different digestion stages. CONCLUSIONS: Sea bass macrophages possess the mechanisms necessary to both engulf and kill bacteria. Cellular and subcellular events in the morphology of phagocytosis and lysosomal dissolution of bacteria fit the general pattern described for mammals. PMID- 7879911 TI - Anatomy of the hyoid apparatus in Odontoceti (toothed whales): specializations of their skeleton and musculature compared with those of terrestrial mammals. AB - BACKGROUND: The hyoid apparatus of odontocetes (toothed whales) serves as a major attachment point for many of the muscles and ligaments subserving breathing, swallowing, and sound production. METHODS: This study examines the hyoid apparatus in 48 specimens of ten odontocete genera (Phocoena, Lagenorhynchus, Stenella, Delphinus, Tursiops, Grampus, Globicephala, Mesoplodon, Physeter, and Kogia) collected post mortem from beach strandings. RESULTS: The odontocete hyoid apparatus, as that of their closest terrestrial relatives, the artiodactyls, is divisible into a basal portion (basihyal, paired thyrohyals) and a suspensory portion (paired ceratohyals, epihyals, stylohyals, and tympanohyals) connecting the basal portion to the skull base. Unlike other terrestrial mammals, the basal portion lies inferior to the laryngeal aditus, is flattened dorso-ventrally, and is relatively large, thus providing a broad surface area for muscle attachments. The suspensory elements are not as flattened and are joined by synovial joints (except for epihyal-stylohyal fusion). Muscular specializations include enlargement of those which retract the hyoid apparatus (e.g., sternohyoid) or control the tongue (e.g., styloglossus, hyoglossus). These muscles may be particularly important in a specialized prey capture behavior called suction feeding. In addition, the hyoid apparatus has a tilted placement, which allows asymmetrical enlargement of the piriform sinuses. Asymmetry is also seen in the muscular attachments between the larynx and the hyoid apparatus. The most pronounced differences from the basic pattern are observed in two families: Physeteridae and Ziphiidae. CONCLUSIONS: The derived position and shape of the odontocete hyoid apparatus may have evolved to subserve several specialized upper respiratory/digestive tract functions, such as simultaneous feeding (suction and swallowing) and sound production. PMID- 7879912 TI - Statistical analysis of compositional data in anatomy. AB - BACKGROUND: Variables which describe the composition, or relative size of components, of an organism need to be analysed in an appropriate manner. METHODS: A few of the appropriate descriptive and inferential techniques have been described and applied to a number of anatomical data sets. RESULTS: When applied to data on the composition of the vastus medialis in adults, a small but significant difference in average muscle fibre type distribution was demonstrated between males and females. There was little evidence for a relationship between fibre type distribution and age over the range considered. CONCLUSIONS: Graphical displays via ternary diagrams are a simple way of illustrating compositional data simultaneously between and within groups. Numerical analysis is likely to involve transformation of original variables before standard univariate or multivariate statistical techniques can be used. PMID- 7879914 TI - New inclusion body in a rat renal cell. AB - BACKGROUND AND METHODS: In an effort to review ultrastructural features of cells in the kidney of a male rat, transmission electron microscopy was used to study ultrathin sections. RESULTS: One light cell in a collecting tubule contained a 2.3-microns long linear array of electron-dense asymmetric structures in a granular zone of greater electron density than the general cytoplasm. This inclusion body could be interpreted to consist of a parallel array of 100-150-nm x 24-nm electron-dense rodlets, or a parallel array of 100-150-nm x 67-nm tubules. The inclusion showed no association with any cell organelle. The origin, chemical nature, frequency of occurrence, and functional significance of this inclusion are unknown. CONCLUSIONS: Although this inclusion body somewhat resembles previously described inclusions or granules, the differences in dimensions, frequency, and relation to other cell structures suggest it is a new observation. PMID- 7879913 TI - Effects of brefeldin A on the three-dimensional structure of the Golgi apparatus in a sensitive strain of Saccharomyces cerevisiae. AB - BACKGROUND: Brefeldin A (BFA), when added to the medium of cultured mammalian cells, induces a reversible block of secretion and disrupts the Golgi apparatus whereas Golgi enzyme markers appear to redistribute into the endoplasmic reticulum (ER). It has been shown in addition that in mammalian cells, BFA would prevent the assembly of coatomer proteins (COP) onto membranes by inhibiting the GTP-dependent interaction of the ADP-ribosylation factor (ARF) with such membranes. The purpose of the present study is to analyze, by stereoelectron microscopy, the structural modifications of Golgi elements and of the ER-Golgi relationship in a BFA-sensitive yeast mutant, S. cerevisiae erg6. METHODS: S. cerevisiae erg6 cells were placed in a medium containing 100 micrograms/ml BFA dissolved in 1% alcohol and collected after exposures of 0.5, 1.5, 5, 10, 15, 20, 30, and 70 min to the drug. Yeasts placed in a BFA-free medium but containing 1% alcohol served as controls. After fixation in 2% glutaraldehyde, the cells were postfixed in reduced osmium and embedded in Epon. Then 0.08-0.2 microns thick sections stained with lead citrate were examined with the electron microscope. Photographs of the thicker sections, tilted at +/- 15 degrees from the 0 degree position of the goniometric stage, were used to prepare stereopairs from which the three-dimensional configuration of the organelles was visualized. Since BFA is known to prevent the interaction of ARF with membranes, the phenotype of the arf1 mutant deficient in this protein was also examined for comparative purposes. RESULTS: In control cells, as in wild-type strains, two types of Golgi elements were observed: small networks of fine tubules seen close and occasionally connected to ER cisternae and coarser tubular networks showing nodular distensions having a size comparable to that of secretion granules. The latter networks were considered as trans-Golgi elements and the former as cis-Golgi elements. Several networks of both types were distributed throughout the cytoplasm. At short time intervals (0.5-5 min) of BFA treatment, the trans-Golgi elements disappeared from the cytoplasm, while the ER-connected cis-Golgi elements developed and formed large spheroidal masses frequently showing concentrically arranged fine tubular networks. Such spheroidal, cage-like structures later disappeared, and after 30 min Golgi elements were no longer identifiable, while ER cisternae assumed pleomorphic configurations as the cells showed signs of degeneration. S. cerevisiae arf1 mutants presented a phenotype similar to that of BFA-treated S. cerevisiae erg6. CONCLUSIONS: It is therefore concluded that soon after exposure to BFA there is, in this sensitive yeast mutant, a transitory hypertrophy of the ER-connected cis-Golgi network presumably resulting from a block at the exit end of this compartment. At longer time intervals (i.e., after 30 min) the Golgi elements are no longer formed, and the cells present signs of cell degeneration. PMID- 7879915 TI - Localization of splenic cells with antigen-transporting capability in the chicken. AB - BACKGROUND: The objective of the present study is to investigate the migration pattern of the splenic dendritic cell of the chicken named the ellipsoid associated cell (EAC) from the site of initial location at the periphery of the ellipsoid to the splenic T- and B-dependent areas. METHODS: Bovine serum albumin bound to biotin and conjugated to gold particles was used as a histochemically identifiable antigen detected as a peroxidase reaction. The antigen was intravenously injected, and subsequently its pattern of distribution in a time sequence and within the tissue was examined at the light and electron microscopy levels. In addition, an hour prior to sacrifice, the chickens received a single injection of the thymidine analogue 5-bromo-2'-deoxyuridine, in order to quantify the number of DNA synthesizing cells and to establish a relationship between the migrating EAC and the rate of mitosis in the white pulp. RESULTS: The observations showed that between 12 hours and 3 days after the second antigen administration the labeled EAC, which was first located around the ellipsoid, progressively reached further areas with time towards the periarteriolar lymphoid sheaths, where newly formed germinal centers appeared. Furthermore, the rate of cell proliferation within the white pulp was associated with the arrival of the antigen-transporting EAC. CONCLUSIONS: The results suggest that migrating EAC have a role as both antigen-transporting cell and antigen-presenting cell in the T- and B-dependent areas, as a result of which migrating EAC is transiently found in periellipsoidal white pulp, then periarteriolar lymphoid sheaths, and finally germinal centers, where it may function as an interdigitating cell or as a follicular dendritic cell, depending on its location. Thus, we conclude that the EACs are precursors of both interdigitating and follicular dendritic cells. PMID- 7879916 TI - Scanning electron microscopic studies of reticular framework in the rat mesenteric lymph node. AB - BACKGROUND: The reticular framework in the lymph node has in the past been studied mainly by light microscopy of silver-impregnated specimens. The aim of the present study is to understand three-dimensionally the ultrastructure and organization of the reticular framework better than before. METHODS: The mesenteric lymph nodes of the rat were prepared either an alkali-water maceration method or a conventional method and were observed in a scanning electron microscope (SEM). RESULTS: The SEM study of alkali-water macerated tissues visualized directly the reticular fiber network in the lymph node. The reticular fibers consisted of thin bundles of collagen fibrils. They were continuous with the collagen fibrillar sheaths of blood vessels and lymphatic sinuses as well as with the fibrous capusule, thus acting as a skeleton of the lymph node. The arrangement of the reticulum was variable, depending on individual compartments. The SEM study of conventionally treated tissues, on the other hand, clarified the shape of reticular cells and their relationship with the reticular fibers. The sinus reticular cells connected with the sinus lining cells but separated from the parenchymal reticular cells, indicating that the former two originate from lymphatic endothelial cells. The parenchymal reticular cells varied in shape depending on their locations but essentially shared features with fibroblasts. CONCLUSIONS: The arrangements of the reticular fibers in the parenchyma were closely related to the associated reticular cells, showing the possibility that the reticular cells maintain the shape of the reticular framework suitable for each compartment of the lymph node. PMID- 7879917 TI - Regeneration in denervated toad (Bufo viridis) gastrocnemius muscle and the promotion of the process by low energy laser irradiation. AB - BACKGROUND: It is known that while denervated skeletal muscles have the ability to regenerate, maturation of regenerated myofibres does not take place under these conditions. Denervation also causes elevation of "invasive" and satellite cells, but the role of these cells in the regeneration process after injury to the denervated muscle is still unknown. Low energy lasers have recently been found to modulate and accelerate physiological processes in cells. The aim of the present study was to compare regeneration in denervated and innervated amphibian muscles and to investigate whether this process in denervated muscles can be stimulated by low energy laser irradiation prior to injury in these muscles. METHODS: Denervated gastrocnemius muscles of toads were irradiated with He-Ne laser (6.0 mW, 31.2 J/cm2) 7 days postdenervation (control muscle received red light irradiation at the same wavelength). Nine days after denervation cold injury was performed on the site of irradiation of both groups of muscles. At 14 days postinjury all muscles were removed and processed for histology and histomorphometric analysis of mononucleated cells, myotubes, and young myofibres in the regenerated zone. RESULTS: The volume fraction (percent of total injured zone) of the various histological structures in the injured zones 14 days after cold injury in the denervated (9 days prior to injury) muscles did not differ from innervated injured muscles at the same time interval postinjury. The mononucleated cells and myotubes in the laser irradiated muscles comprised 49 +/- 4% and 6 +/- 1% of the injured area, respectively, which was significantly lower than their volume fraction (67 +/- 2% and 11 +/- 2%, respectively) in the control muscles. The young myofibres populated 34 +/- 4% of the total injured area in the denervated and laser irradiated muscles which was significantly higher than their volume fraction (12 +/- 2%) in control denervated muscles. CONCLUSIONS: It is concluded that initial stages of regeneration can also take place in skeletal denervated and injured muscles of amphibians. The kinetics of the regeneration process are identical in denervated and innervated muscles. The process of regeneration in denervated muscles can be markedly enhanced if the muscle is irradiated by low energy laser prior to injury, probably by activation (stimulation of proliferation and/or differentiation) cells in the muscles that are "recruited" and participate in the process of regeneration. PMID- 7879918 TI - Ultrastructure and immunohistochemistry of the embryonic type of fat identified in the human infant breast. AB - In this paper we describe the light and electron microscopic appearance of the embryonic type of fat in human infant breast, together with immunocytochemical findings. This fat tissue was composed of numerous capillaries surrounded by a mixed population of undifferentiated mesenchymal cells and preadipocytes at various stages of differentiation. The preadipocytes were characterised by a number of cytoplasmic processes, varying numbers of lipid droplets, and an envelope of electrondense material outside the cell membrane. Immunocytochemistry showed a characteristic distribution of collagen type IV adjacent to and vimentin and S100 protein within the preadipocytes. This is the first report of the ultrastructure of the human mammary embryonic type of fat. The possible role of the embryonic type of fat in the development and growth of the human breast is discussed. PMID- 7879919 TI - Apical structures of "mitochondria-rich" alpha and beta cells in euryhaline fish gill: their behaviour in various living conditions. AB - BACKGROUND: One of the characteristic features of the two types (alpha and beta) of "mitochondria-rich" (chloride) cells in the gill epithelium of freshwater fishes is the presence in their apical region of tubulovesicular structures. A further analysis of the ultrastructural features of these apical elements as well as that of their modifications under various living conditions should help to understand better the respective role of both alpha and beta cells in these conditions. METHODS: Atlantic salmon (Salmo salar) maintained in fresh water as well as tilapia (Oreochromis niloticus) maintained either in fresh water or in deionized water or in 20% saltwater were examined. Measurements of surface areas of apical structures in the various living conditions were also performed. RESULTS: In the alpha cells of freshwater fishes, the apical structures consisted of isolated vesicles containing a filamentous material resembling that coating the apical surface. They were closely related to the apical plasma membrane and did not penetrate the region containing the tubular system. When fishes were transferred to deionized water, the number of the apical membrane folds increased significantly, as did the number and size of apical structures which became elongated. In saltwater-adapted fishes, the apical structures showed a tendency to collapse and took the appearance of flattened and slightly curved elements. These observations tended to indicate that in alpha cells the apical structures were extensions of the apical plasma membrane and thereby might be implicated in sodium uptake when fishes are placed in fresh or deionized water and in chloride excretion when they are transferred to salt water. In beta cells, the apical structures were usually separated from the apical plasma membrane by a zone rich in cytoskeleton elements. They penetrated deeply into the supranuclear region, where they intermingled with the elements of the tubular system. They consisted mainly of tubular elements that contained a material resembling that present in the trans tubular Golgi network from which they might originate. The apical structures remained unaltered in beta cells whatever the medium (fresh or deionized water) in which the fish was placed. CONCLUSIONS: The alpha cells which are usually thought to be mainly involved in chloride excretion when fishes are transferred into seawater might also be implicated in sodium uptake in freshwater living conditions. The role of beta cells, in contrast, still remains to be established. PMID- 7879920 TI - Serotonin-containing projections to the mesencephalic trigeminal nucleus of the cat. AB - BACKGROUND: It is well known that the mesencephalic trigeminal nucleus (MTN) neurons transmit somatosensory information from proprioceptors in the oral-facial region. Several mechanisms of sensory transduction in these specialized receptors have been proposed, but the neurotransmitters which are responsible for mediating proprioceptive information are still unknown. The current study concentrates on the distribution of one putative neurotransmitter system, serotonin (SER), in the cat MTN. A second objective was to clarify the location and sources of serotoninergic projections on the MTN neurons. METHODS: To determine whether SER was localized in the MTN, the peroxidase-antiperoxidase (PAP) immunocytochemical technique was applied at light and electron microscopic levels in colchicine treated animals. The origin of SER-containing fibers in the MTN was studied using a double-labeling method combining retrograde transport with wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and SER immunocytochemistry. RESULTS: There were no SER-containing neurons in the MTN. The cell bodies of immunonegative MTN neurons were closely surrounded by fine SER positive fibers and terminals. The labeled fibers were in most cases very thin and sometimes varicose. Ultrastructurally, direct synaptic contacts between SER containing terminals and perikarya of MTN neurons of all sizes could be seen. The majority of SER-labeled structures were synaptic terminals in which the immunoreactive material was located within the small round clear as well as the small granular vesicles (diameter 50-80 nm) and a few large dense-cored vesicles (up to 150 nm). Retrograde tracing demonstrated that most of cells in the nuclei raphe dorsalis, pontis and magnus were WGA-HRP-labeled. CONCLUSIONS: These results indicated that MTN neurons received serotoninergic projections from the raphe nuclei of the brainstem. In light of these morphological data, it is concluded that the MTN of the cat is under the influence of SER-containing axons and this serotoninergic input may modulate MTN neuronal activity at the first synaptic relay. PMID- 7879922 TI - Variation in articular cartilage in rabbits between weeks six and eight. AB - BACKGROUND: Previous studies of variation in cartilage characteristics with age have involved comparison of young and adult individuals, but no data on short term age-related change are available. Such data are important for studies of the response of cartilage to experimental stimuli in young rabbits, to distinguish the response to the stimuli from accompanying age-related changes. METHODS: We used light microscopy to study the thickness, cell density, and degree of histological definition of articular cartilage on the femoral trochlea of 6-, 7-, and 8-week-old rabbits. RESULTS: Thickness and cell density both decline significantly with age. The decline in cell density is more marked in surface layers of cartilage and is accompanied by an increase in the safranin O-staining affinity of the extracellular matrix and an extension of this affinity towards the surface. CONCLUSIONS: Our results indicate that the synthesis of matrix components becomes more important relative to proliferative activity. The traditionally defined histological layers (zones I, II, III, and IV) are not clearly distinguishable in rabbits of this age. In 6- and 7-week old animals only a "surface" (I/II) and a "deep" layer (III) can be distinguished. By 8 weeks, zones I and II are well defined but the mineralization front (marking the boundary between zones III and IV) is still absent. PMID- 7879921 TI - Relation between the trans-Golgi network and the Golgi stack on development of the Golgi apparatus of the ameloblast in developing rat molar tooth germs. AB - BACKGROUND: The problem of how the functional compartments of the Golgi apparatus organizes during cell differentiation to become a well-formed Golgi apparatus is as yet an unresolved issue. This study was designed to define the involvement of the trans-Golgi network (TGN) and the Golgi stack in organizing the Golgi apparatus. METHODS: The distribution of the TGN marker enzyme was examined in the ameloblast of developing rat molar tooth germs using cytochemistry with Co-enzyme A phosphatase (CoA Pase) and cytidine monophosphatase (CMPase). RESULTS: Typically formed Golgi apparatus was observed in the secretory ameloblast but not in the presecretory ameloblast. Organization of the Golgi apparatus through the presecretory ameloblast was noted. In the presecretory ameloblast, Golgi stacks of different sizes and clusters of small vesicles were located in the cytoplasm lateral to the nucleus. The saccules with enzymes marked for TGN were also observed in the cytoplasm lateral to the nucleus. These saccules were adjacent to the cluster of small vesicles and/or the Golgi stack. Upon cell differentiation, Golgi stacks were seen in line along the long axis of the cell, and the file of the stacks in the cytoplasm lateral to the nucleus was formed. The positive saccule was seen in a parallel line equal to the length of the Golgi stacks. CONCLUSIONS: In organizing the Golgi apparatus, the development process of the TGN and the Golgi stack appear to be different, and new Golgi stacks seem to be formed through the accumulation of small vesicles near the pre-existing TGN. PMID- 7879924 TI - Changes in the arrangement of actin filaments in myoid cells and Sertoli cells of rat testes during postnatal development and after experimental cryptorchidism. AB - BACKGROUND: Abundant actin filaments are present in myoid cells and Sertoli cells in the testis. In the adult rat, the filaments form a lattice arrangement within the myoid cell, and show a hexagonal pattern in the basal junctional regions of Sertoli cells. METHODS: Isolated seminiferous tubules and frozen sections were prepared from juvenile to adult Wistar rat testes, stained with FITC-conjugated phalloidin, and observed by confocal microscopy. Unilateral cryptorchidism was induced in adult rats, and seven days later, their testes were also examined. RESULTS: In the myoid cell, parallel actin filaments running circularly around the seminiferous tubules were observed at 15 and 20 days of age. Then, at 30 days, actin filaments arranged longitudinally along the tubular long axis appeared in addition to the circular bundles. A lattice arrangement of actin filament bundles in myoid cells became obvious at 40 days, when elongated spermatids are found in the tubule. Actin filaments in the basal junctional regions of Sertoli cells did not acquire the hexagonal pattern seen in the adult testis until 30 days of age. In the cryptorchid testes, the arrangement of actin filaments in the both cells showed a remarkable change compared to the control testis; the filaments became thinner and disrupted. CONCLUSIONS: A lattice arrangement of the actin filaments in the myoid cell appear at around 30 days, before the completion of spermatogenesis. A hexagonal pattern of the filaments in the junctional regions of Sertoli cells has already developed at this age. Cryptorchidism affects the actin filaments of the both cells. PMID- 7879923 TI - Transmission electron microscopic demonstration of vimentin in rat osteoblast and osteocyte cell bodies and processes using the immunogold technique. AB - BACKGROUND: The immunogold labeling technique and transmission electron microscopy were used to demonstrate the expression and position of the intermediate filament vimentin in rat osteoblast and osteocyte cell bodies and cell processes. Conventional light and transmission electron microscopic studies of bone cells demonstrated adjacent cell linkage to be mediated by osteoblast and osteocyte processes present within the canalicular system traversing the bone matrix. The cell processes were filled with densely packed filaments, many of which have been shown previously to be actin microfilaments. The appearance, however, of 10 nm diameter filaments in some cell processes and the fact the intermediate filament vimentin has been defined in many cells of mesenchymal origin raised the possibility that some of these filaments might be vimentin. The ultrastructural colloidal gold immunochemical technique allowed for demonstration in situ of the expression of vimentin filaments plus accurate definition of their position. METHODS: The studies were performed in newborn rat femoral and tibial diaphyseal cortical bone and in 1-week-old repair bone from 2.4 mm diameter defects made through the lateral cortex in 6-week-old rat femurs and tibias. The bone tissues for the immunochemical study were fixed in 1% glutaraldehyde, 4% paraformaldehyde, and 0.1 M phosphate buffer (pH 7.4) for 2 days. Decalcification was performed in 6% EDTA for 2-3 days. Infiltration involved use of Lowicryl resin K4M, and the embedding and curing processes were performed in a cryostat with temperatures -30 degrees C. An antivimentin monoclonal antibody was used for labeling using the postembedding technique. Effective antibody dilutions ranged from 1:10 to 1:200, with the dilutions of 1:25 and 1:100 showing the best combination of filament labeling with the least matrix background. The grids were exposed to 10 nanometer gold colloid conjugated goat anti-mouse IgM for demonstration of binding. RESULTS: Vimentin immunolabeling was defined clearly in relation to filaments within the osteoblast and osteocyte cell body cytoplasm, throughout the entire length of the osteoblast and osteocyte cell processes, and in close relationship to the intracellular gap junctions which were present within the cell processes both close to the cell bodies and within the canaliculi well away from them. CONCLUSIONS: Immunogold labeling demonstrates the presence of the intermediate filament vimentin in osteoblast and osteocyte cell bodies and processes of rat bone. Vimentin distribution is not concentrated to specific areas, is present throughout the extent of the bodies and processes, and is seen immediately adjacent to gap junctions. PMID- 7879925 TI - Apoptosis of cultured mouse luteal cells induced by tumor necrosis factor-alpha and interferon-gamma. AB - BACKGROUND: Macrophages and T lymphocytes have been identified in the regressing corpus luteum, and they are thought to participate in structural luteolysis (destruction and removal of luteal cells). Since these cells produce cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), we investigated the effects of these two cytokines on death of luteal cells in vitro. METHODS: Mouse luteal cells were cultured in serum-free medium with TNF alpha at 0, 500, 1,000, 3,000, or 5,000 U/ml in the presence or absence of IFN gamma at 1,000 U/ml for 3 or 6 days. Then, for estimation of the actions of these cytokines on induction of luteal cell death, we determined the number of viable cells, the percentage of fragmented DNA in total DNA extracted from cultured cells, and the percentage of cells with fragmented DNA in their nuclei by the trypan blue exclusion test, the sensitive micromethod for DNA assay, and the in situ DNA 3' end labeling method, respectively. DNA fragmentation was also analysed by agarose gel electrophoresis, and cultured cells were examined by electron microscopy. RESULTS: On day 3 of culture, IFN-gamma alone at 1,000 U/ml or TNF-alpha alone at 500-5,000 U/ml did not decrease the number of viable cells, but a combination of IFN-gamma (1,000 U/ml) and TNF-alpha (5,000 U/ml) did. On day 6, IFN-gamma alone at 1,000 U/ml or TNF-alpha alone at 500, 1,000 and 3,000 U/ml did not decrease the number of viable cells, whereas TNF-alpha alone at 5,000 U/ml did, and combinations of IFN-gamma and TNF-alpha at 1,000, 3,000, and 5,000 U/ml decreased the number of viable cells in proportion to the concentration of TNF-alpha. On days 3-6 of culture, combinations of IFN-gamma and TNF-alpha that decreased the number of viable cells also increased the percentages of fragmented DNA in total DNA of cultured luteal cells and the percentages of luteal cells with fragmented DNA in their nuclei. Agarose gel electrophoresis of fragmented DNA showed a ladder-like pattern, and electron microscopic examination showed luteal cells with the characteristics of apoptosis. CONCLUSIONS: The presence of IFN-gamma modulates the ability of TNF alpha to induce a reduction in the number of viable cells, although TNF-alpha alone at high concentrations can induce a reduction in the number of viable cells. PMID- 7879926 TI - Actin, alpha-actinin, and spectrin with specific associations with the postacrosomal and acrosomal domains of bovine spermatozoa. AB - BACKGROUND: Characteristic membrane changes in spermatozoa culminating in acrosome reaction and sperm-egg fusion, and suspected involvement of actin containing cytoskeleton in membrane changes in general, prompted us to investigate subcellular distribution of actin and actin-binding proteins in bovine spermatozoa subjected to various extractions which sequentially denude the sperm investments. METHODS: Spermatozoa were treated with either 1% SDS, 0.1% Triton X-100, 0.1% Hyamine, or 1 M MgCl2 or were sonicated. Immunostaining of actin, alpha-actinin, spectrin, and acrosin as well as electron microscopic analysis of extracted spermatozoa were carried out. RESULTS: Extractions caused evagination of the acrosomal lamina which retained focal contacts with the inner acrosomal membrane. Extractions further revealed lateral prongs at the anterior border of the postacrosomal sheath. Labeling for alpha-actinin and spectrin was localized in the acrosin-positive acrosomal lamina, neck, and principal piece, the latter containing also relatively extraction-resistant oligomeric or polymerized actin. In the postacrosomal area, actin was accumulated in the extraction-resistant posterior ring structure and anteriorly at the sites apparently related to the lateral prongs. Notably, spectrin reactivity was enhanced by MgCl2 in head, neck, and principal piece, and sonication abolished cytoskeletal immuno-reactivity in the head. CONCLUSIONS: Destabilization of membranes with selected extractions induces changes in the acrosomal lamina mimicking acrosomal vesicle formation. The lateral prongs and posterior ring structure, respectively, may serve as anterior and posterior anchors for the extraction-resistant post-acrosomal sheath. The lateral prongs may also be a merger zone for actin, alpha-actinin, and spectrin with important implication on sperm function. The latter two proteins may be involved in acrosomal vesicle formation. It is apparent that extractions have a significant effect on the detectability of sperm cytoskeletal elements. PMID- 7879927 TI - Postnatal growth of lung parenchyma in the piglet: morphometry correlated with mechanics. AB - BACKGROUND: A previous study of piglet lung growth (Mansell et. al. 1989. J. Appl. Physiol., 67:1422-1427) showed transient stiffness to changes in shape and volume immediately after birth. Later, elastic recoil was found to increase as the lung grew in weight and volume. The present study uses morphometry to test possible structural correlates of these two mechanical changes. METHODS: Piglet lungs were fixed near full inflation via the airways during the immediate newborn period (6-12 hours, n = 3), at 3-5 days (n = 6), 25-30 days (n = 5), and 80-85 days (n = 3). Morphometry comprised arithmetic and harmonic mean thicknesses of alveolar septae and average mean surface curvature. Measurements of curvature and airspace volume were combined to differentiate alveolar expansion from septal proliferation as mechanisms for volumetric growth. RESULTS: The unique mechanical behavior of the newborn lungs was associated with relatively thick alveolar septae. Marked thinning of the septae and resolution of the stiffness to shape and volume change had occurred by 3-5 days. An increase in elastic recoil during the first postnatal month was found to be associated with simple airspace expansion. The second and third months were characterized by septal proliferation and increase in arithmetic mean septal thickness but elastic recoil did not increase further. Harmonic mean septal thickness and airspace volume per gram of lung tissue did not change over the course of the study. CONCLUSIONS: 1) A relative stiffness to shape and volume change in freshly newborn piglet lungs is associated with relatively thick alveolar septal walls; 2) postnatal development of piglet lung parenchyma involves septal lengthening and thinning followed by septal proliferation; 3) the initial phase of septal lengthening, rather than the later phase of septal proliferation, is associated with increase in parenchymal recoil. PMID- 7879928 TI - Shibboleths and jigsaw puzzles. The fluoride nephrotoxicity enigma. PMID- 7879929 TI - Low-frequency spectral power of heart rate variability is not a specific marker of cardiac sympathetic modulation. AB - BACKGROUND: Heart rate variability in the frequency domain has been proposed to reflect cardiac autonomic control. Therefore, measurement of heart rate variability may be useful to assess the effect of epidural anesthesia on cardiac autonomic tone. Accordingly, the effects of preganglionic cardiac sympathetic blockade by segmental epidural anesthesia were evaluated in humans on spectral power of heart rate variability. Specifically, the hypothesis that cardiac sympathetic blockade attenuates low-frequency spectral power, assumed to reflect cardiac sympathetic modulation, was tested. METHODS: Ten subjects were studied while supine and during a 15-min 40 degrees head-up tilt both before and after cardiac sympathetic blockade by segmental thoracic epidural anesthesia (sensory block: C6-T6). ECG, arterial pressure, and respiratory excursion (Whitney gauge) were recorded, and a fast-Fourier-transformation was applied to 512-s data segments of heart rate derived from the digitized ECG at the end of each intervention. RESULTS: With cardiac sympathetic blockade alone and the subjects supine, both low-frequency (LF, 0.06-0.15 Hz) and high-frequency (HF, 0.15-0.80 Hz) spectral power remained unchanged. During tilt, epidural anesthesia attenuated the evoked increase in heart rate (+11.min-1 +/- 7 SD vs. +6 +/- 7, P = 0.024). However, while during tilt cardiac sympathetic blockade significantly decreased the LF/HF ratio (3.68 +/- 2.52 vs. 2.83 +/- 2.15, P = 0.041 vs. tilt before sympathetic blockade), a presumed marker of sympathovagal interaction, absolute and fractional LF and HF power did not change. CONCLUSIONS: Although preganglionic cardiac sympathetic blockade reduced the LF/HF ratio during tilt, it did not alter spectral power in the LF band during rest or tilt. Accordingly, low-frequency spectral power is unlikely to specifically reflect cardiac sympathetic modulation in humans. PMID- 7879930 TI - Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. The Study of Perioperative Ischemia Research Group. AB - BACKGROUND: Dexmedetomidine, a highly selective alpha 2-adrenergic agonist, increases perioperative hemodynamic stability in healthy patients but decreases blood pressure and heart rate. The goal of this study was to evaluate, in a preliminary manner, the hemodynamic effects of perioperatively administered dexmedetomidine in surgical patients at high risk for coronary artery disease. METHODS: Twenty-four vascular surgery patients received a continuous infusion of placebo or one of three doses of dexmedetomidine, targeting plasma concentrations of 0.15 ng/ml (low dose), 0.30 ng/ml (medium dose), or 0.45 ng/ml (high dose) from 1 h before induction of anesthesia until 48 h postoperatively. All patients received standardized anesthesia and hemodynamic management. Blood pressure, heart rate, and Holter ECG were monitored; additional monitoring included continuous 12-lead ECG preoperatively, anesthetic concentrations and myocardial wall motion (echocardiography) intraoperatively, and cardiac enzymes postoperatively. RESULTS: Preoperatively, there was a decrease in heart rate (low dose 11%, medium dose 5%, high dose 20%) and systolic blood pressure (low dose 3%, medium dose 12%, high dose 20%) in patients receiving dexmedetomidine. Intraoperatively, dexmedetomidine groups required more vasoactive medications to maintain hemodynamics within predetermined limits. Postoperatively, demedetomidine groups had less tachycardia (minutes/monitored hours) than the placebo group (placebo 23 min/h; low dose 9 min/h, P = 0.006; medium dose 0.5 min/h, P = 0.004; high dose 2.3 min/h, P = 0.004). Bradycardia was rare in all groups. There were no myocardial infarctions or discernible trends in the laboratory results. CONCLUSIONS: Infusion of dexmedetomidine up to a targeted plasma concentration of 0.45 ng/ml appears to benefit perioperative hemodynamic management of surgical patients undergoing vascular surgery but required greater intraoperative pharmacologic intervention to support blood pressure and heart rate. PMID- 7879932 TI - Additive interactions between propofol and ketamine when used for anesthesia induction in female patients. AB - BACKGROUND: Propofol and ketamine may be paired for anesthesia induction and for total intravenous anesthesia. The nature of any sedative interactions occurring between propofol and ketamine are unknown. The combination when used for anesthesia induction in female patients was studied. METHODS: Quantal dose response curves were determined in 180 female patients to whom the drugs were administered individually and in combination. Two minutes after administering the drugs, two endpoints were assessed. First, loss of response to verbal command (hypnosis) and then, in those who failed to respond to this endpoint, loss of response to a 5-s transcutaneous tetanus (anesthesia). Interactions were analyzed by fitting the data to a mathematical model in which response was analyzed in terms of the doses of the two drugs and an additional term included to describe nonadditive interactions. The incidences of apnea, arterial pressure, and heart rate changes during the first 5 min were recorded. RESULTS: At the hypnotic endpoint, the ED50s were 1.10 mg/kg propofol (95% CIs 0.93-1.27), 0.39 mg/kg ketamine (95% CIs 0.27-0.46), and the combination of 0.63 mg/kg propofol and 0.21 mg/kg ketamine (95% CIs 0.53/0.18-0.73/0.24). At the anesthetic endpoint, the ED50s were 1.85 mg/kg propofol (95% CIs 1.58-2.36) 0.66 mg/kg ketamine (95% CIs 0.58-0.77), and the combination of 1.05 mg/kg propofol and 0.35 mg/kg ketamine (95% CIs 0.88/0.29-1.27/0.42). The effects were additive at both endpoints; there was no evidence of an interaction. The ED50s for apnea were 1.61 mg/kg propofol (95% CIs 1.39-1.94), greater than 0.85 mg/kg ketamine and for the combination 1.50 mg/kg propofol and 0.50 mg/kg ketamine (95% CIs 1.15/0.38-3.09/1.03). The addition of ketamine did not significantly alter the ED50 for apnea of propofol. There was a significant difference in the arterial pressures among the three groups (P < 0.001). Using the combination, the cardiostimulant effects of ketamine balanced the cardiodepressant effects of propofol. There was no change in arterial pressure or heart rate after the noxious stimulus. CONCLUSIONS: When using the combination, doses were additive at hypnotic and anesthetic endpoints. Ketamine had no influence on the incidence of apnea after propofol, and the net hemodynamic effects were minimal. PMID- 7879931 TI - Intraperitoneal versus interpleural morphine or bupivacaine for pain after laparoscopic cholecystectomy. AB - BACKGROUND: Opioids can produce peripheral analgesic effects by activation of opioid receptors on sensory nerves. This study was designed (1) to examine a novel route of opioid administration, the intraperitoneal injection; (2) to compare this to interpleural application, and (3) to compare opioid with local anesthetic effects under both conditions. METHODS: At the end of laparoscopic cholecystectomy, 110 patients received the following injections in a double blind, randomized manner: Group 1 (n = 18) was given intraperitoneal morphine (1 mg in 20 ml saline) and 20 ml intravenous saline. Group 2 (n = 17) received intraperitoneal saline and 1 mg intravenous morphine. Group 3 (n = 15) received 20 ml 0.25% intraperitoneal bupivacaine and intravenous saline. Group 4 (n = 20) received interpleural morphine (1.5 mg in 30 ml saline) and 30 ml intravenous saline. Group 5 (n = 20) received interpleural saline and 1.5 mg intravenous morphine. Group 6 (n = 20) received 30 ml 0.25% interpleural bupivacaine and intravenous saline. Postoperative pain was assessed using a visual analog scale, a numeric rating scale, and the McGill pain questionnaire. Pain localization, supplemental analgesic consumption, vital signs, and side effects were recorded for 24 h. RESULTS: Neither intraperitoneal nor interpleural morphine produced significant analgesia after laparoscopic cholecystectomy (P > 0.05, Kruskal Wallis test), whereas interpleural bupivacaine was effective (P < 0.05, Kruskal Wallis test, up to 6 h postoperatively) but not intraperitoneal bupivacaine (P > 0.05, Kruskal-Wallis test). Shoulder pain was not prevalent in the majority of patients during the first 6 h. By 24 h, about half of the patients complained of shoulder pain, which was rated "low" by about one-third of all patients. No significant side effects occurred. CONCLUSIONS: Interpleural bupivacaine (0.25%) produces analgesia after laparoscopic cholecystectomy. We attribute the lack of effect of intraperitoneal injections to the small dose and to a rapid dilution within the peritoneal cavity. The fact that interpleural morphine (0.005%) is ineffective may be due to an intact perineurial barrier in the noninflamed pleural cavity, which restricts the transperineurial passage of morphine to opioid receptors on intercostal nerves. PMID- 7879933 TI - Comparison of the neuromuscular blocking effect of atracurium and vecuronium on the adductor pollicis and the geniohyoid muscle in humans. AB - BACKGROUND: Residual paralysis of suprahyoid muscles may occur when the adductor pollicis response has completely recovered after the administration of a neuromuscular blocking agent. The response of the geniohyoid muscle to intubating doses of muscle relaxants is evaluated and compared to that of adductor pollicis. METHODS: Sixteen patients undergoing elective surgery under general anesthesia were given 5-7 mg.kg-1 thiopental and 2 micrograms.kg-1 fentanyl intravenously for induction of anesthesia. Eight (half) patients then received 0.5 mg.kg-1 atracurium, and the other eight received 0.1 mg.kg-1 vecuronium. The evoked response (twitch height, TH) of the adductor pollicis was monitored by measuring the integrated electromyographic response (AP EMG) on one limb and the mechanical response, using a force transducer (AP force), on the other. The activity of geniohyoid muscle (GH EMG) was measured using submental percutaneous electrodes. The following variables were measured: maximal TH depression; onset time for neuromuscular blockade to 50%, 90%, and maximal TH depression (OT50, OT90, and OTmax); times between administration of neuromuscular blocking agent and TH recovery to 10%, 25%, 50%, 75%, and 90% of control; and time for return of train of-four ratio to return to 0.7. RESULTS: The principal findings were (1) OTmax was significantly (P < 0.01) shorter for geniohyoid than for adductor pollicis after either atracurium or vecuronium (OTmax was 216, 256, and 175 s for AP force, AP EMG, and GH EMG, with atracurium and 181, 199, and 144 s with vecuronium, respectively), and (2) the evoked EMG of geniohyoid recovered at the same speed as the EMG of adductor pollicis after an intubating dose of atracurium or vecuronium (recovery of TH to 75% of control at 50, 48, 42 min with AP force, AP EMG, and GH EMG with atracurium and 46, 45, and 42 min with vecuronium, respectively). CONCLUSIONS: Once the adductor pollicis response has returned to normal values after a single intubating dose of atracurium or vecuronium, the risk of residual depression of the TH of the geniohyoid muscle, one of the principal muscles contributing to airway patency, appears unlikely. PMID- 7879934 TI - Cerebrovascular carbon dioxide reactivity in carotid artery disease. Relation to intraoperative cerebral monitoring results in 100 carotid endarterectomies. AB - BACKGROUND: In patients with carotid artery disease, poor intracerebral collateralization is reflected by impaired cerebrovascular reactivity to carbon dioxide inhalation, which will improve after endarterectomy. The relationship between preoperative reactivity to carbon dioxide using transcranial Doppler sonography (TCD) and intraoperative changes of somatosensory evoked potentials (SEP) and TCD parameters were investigated. METHODS: In 94 patients, preoperative carbon dioxide reactivity was examined and defined impaired if mean blood flow velocity in the middle cerebral artery (Vm-MCA) increased less than 1.5% mmHg during carbon dioxide challenge. Patients then underwent 100 carotid operations under general anesthesia with both SEP and TCD monitoring. Shunts were placed if SEP amplitude decreased to less then 50% of control or central conduction time increased by 20% after clamping (critical SEP changes). TCD changes were defined as critical in case of a postclamping/preclamping Vm-MCA ratio < or = 0.4. The incidence of critical SEP and TCD changes was compared to preoperative carbon dioxide testing using Fisher's exact test with P < 0.05 considered significant. Postoperatively, neurologic state and carbon dioxide responsiveness were re examined. RESULTS: Twelve patients showed impaired preoperative carbon dioxide reactivity on the side of operation, which improved markedly after surgery. The incidence of critical SEP changes in these cases (8.3%) was not significantly different from that in the remaining patients (14.8%). Critical SEP changes were significantly correlated with critical TCD changes (P < 0.0001). CONCLUSIONS: Patients with poor carbon dioxide reactivity (preoperative TCD testing) did not have an increased risk of cerebral ischemia during carotid surgery, as assessed by intraoperative SEP recording. PMID- 7879935 TI - Heat flow and distribution during induction of general anesthesia. AB - BACKGROUND: Core hypothermia after induction of general anesthesia results from an internal core-to-peripheral redistribution of body heat and a net loss of heat to the environment. However, the relative contributions of each mechanism remain unknown. The authors evaluated regional body heat content and the extent to which core hypothermia after induction of anesthesia resulted from altered heat balance and internal heat redistribution. METHODS: Six minimally clothed male volunteers in an approximately 22 degrees C environment were evaluated for 2.5 control hours before induction of general anesthesia and for 3 subsequent hours. Overall heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Arm and leg tissue heat contents were determined from 19 intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot temperature. To separate the effects of redistribution and net heat loss, we multiplied the change in overall heat balance by body weight and the specific heat of humans. The resulting change in mean body temperature was subtracted from the change in distal esophageal (core) temperature, leaving the core hypothermia specifically resulting from redistribution. RESULTS: Core temperature was nearly constant during the control period but decreased 1.6 +/- 0.3 degree C in the first hour of anesthesia. Redistribution contributed 81% to this initial decrease and required transfer of 46 kcal from the trunk to the extremities. During the subsequent 2 h of anesthesia, core temperature decreased an additional 1.1 +/- 0.3 degree C, with redistribution contributing only 43%. Thus, only 17 kcal was redistributed during the second and third hours of anesthesia. Redistribution therefore contributed 65% to the entire 2.8 +/- 0.5 degree C decrease in core temperature during the 3 h of anesthesia. Proximal extremity heat content decreased slightly after induction of anesthesia, but distal heat content increased markedly. The distal extremities thus contributed most to core cooling. Although the arms constituted only a fifth of extremity mass, redistribution increased arm heat content nearly as much as leg heat content. Distal extremity heat content increased approximately 40 kcal during the first hour of anesthesia and remained elevated for the duration of the study. CONCLUSIONS: The arms and legs are both important components of the peripheral thermal compartment, but distal segments contribute most. Core hypothermia during the first hour after induction resulted largely from redistribution of body heat, and redistribution remained the major cause even after 3 h of anesthesia. PMID- 7879936 TI - Optimal duration and temperature of prewarming. AB - BACKGROUND: Core hypothermia developing immediately after induction of anesthesia results largely from an internal core-to-peripheral redistribution of body heat. Although difficult to treat, redistribution can be prevented by prewarming. The benefits of prewarming may be limited by sweating, thermal discomfort, and efficacy of the warming device. Accordingly, the optimal heater temperature and minimum warming duration likely to substantially reduce redistribution hypothermia were evaluated. METHODS: Sweating, thermal comfort, and extremity heat content were evaluated in seven volunteers. They participated on two study days, each consisting of a 2-h control period followed by 2 h of forced-air warming with the heater set on "medium" (approximately 40 degrees C) or "high" (approximately 43 degrees C). Arm and leg tissue heat contents were determined from 19 intramuscular needle thermocouples, ten skin temperatures, and "deep" foot temperature. RESULTS: Half the volunteers started sweating during the second hour of warming. None of the volunteers felt uncomfortably warm during the first hour of heating, but many subsequently did. With the heater set on "high," arm and leg heat content increased 69 kcal during the first 30 min of warming and 136 kcal during the first hour of warming, representing 38% and 75%, respectively, of the values observed after 2 h of warming. The increase was only slightly less when the heater was set to "medium." CONCLUSIONS: Neither sweating nor thermal discomfort limited heat transfer during the first hour of warming. Thirty minutes of forced-air warming increased peripheral tissue heat content by more than the amount normally redistributed during the first hour of anesthesia. The large increase in arm and leg heat content during prewarming thus explains the observed efficacy of prewarming. PMID- 7879938 TI - Volatile anesthetic actions on contractile proteins in membrane-permeabilized small mesenteric arteries. AB - BACKGROUND: Volatile anesthetics have been shown to have vasodilating or vasoconstricting actions in vitro that may contribute to their cardiovascular effects in vivo. However, the precise mechanisms of these actions in vitro have not been fully elucidated. Moreover, there are no data regarding the mechanisms of volatile anesthetic action on small resistance arteries, which play a critical role in the regulation of blood pressure and blood flow. METHODS: With the use of isometric tension recording methods, volatile anesthetic actions were studied in intact and beta-escin-membrane-permeabilized smooth muscle strips from rat small mesenteric arteries. In experiments with intact muscle, the effects of-halothane (0.25-5.0%), isoflurane (0.25-5.0%), and enflurane (0.25-5.0%) were investigated on high K(+)-induced contractions at 22 degrees C and 35 degrees C. All experiments were performed on endothelium-denuded strips in the presence of 3 microM guanethidine and 0.3 microM tetrodotoxin to minimize the influence of nerve terminal activities. In experiments with membrane-permeabilized muscle, the effects of halothane (0.5-4.0%), isoflurane (0.5-4.0%), and enflurane (0.5-4.0%) on the half-maximal and maximal Ca(2+)-activated contractions were examined at 22 degrees C in the presence of 0.3 microM ionomycin to eliminate intracellular Ca2+ stores. RESULTS: In the high K(+)-stimulated intact muscle, all three anesthetics generated transient contractions, which were followed by sustained vasorelaxation. The IC50 values for this vasorelaxing action of halothane, isoflurane, and enflurane were 0.47 vol% (0.27 mM), 0.66 vol% (0.32 mM), and 0.53 vol% (0.27 mM), respectively, at 22 degrees C and were 3.36 vol% (0.99 mM), 3.07 vol% (0.69 mM), and 3.19 vol% (0.95 mM), respectively, at 35 degrees C. Ryanodine (10 microM) eliminated the anesthetic-induced contractions but had no significant effect on the anesthetic-induced vasorelaxation in the presence of high K+. In addition, no significant differences were observed in the dose dependence of the direct vasodilating action among these anesthetics with or without ryanodine at either the low or the high temperature. However, significant differences were observed in the vasoconstricting actions among the anesthetics, and the order of potency was halothane > enflurane > isoflurane. The Ca(2+)-tension relation in the membrane-permeabilized muscle yielded a half-maximal effective Ca2+ concentration (EC50) of 2.02 microM. Halothane modestly but significantly inhibited 3 microM (approximately the EC50) and 30 microM (maximal) Ca(2+) induced contractions. Enflurane slightly but significantly inhibited 3 microM but not 30 microM Ca2+ contractions. Isoflurane did not significantly inhibit either 3 microM or 30 microM Ca2+ contractions. CONCLUSIONS: Halothane, isoflurane, and enflurane have both vasoconstricting and vasodilating actions on isolated small splanchnic resistance arteries. The direct vasoconstricting action appears to result from Ca2+ release from the ryanodine-sensitive intracellular Ca2+ store. The vasodilating action of isoflurane in the presence of high K+ appears to be attributable mainly to a decrease in intracellular Ca2+ concentration, possibly resulting from inhibition of voltage-gated Ca2+ channels. In contrast, the vasodilating actions of halothane and enflurane in the presence of high K+ appears to involve inhibition of Ca2+ activation of contractile proteins as well as a decrease in intracellular Ca2+ concentration in smooth muscle. PMID- 7879937 TI - Human kidney methoxyflurane and sevoflurane metabolism. Intrarenal fluoride production as a possible mechanism of methoxyflurane nephrotoxicity. AB - BACKGROUND: Methoxyflurane nephrotoxicity is mediated by cytochrome P450 catalyzed metabolism to toxic metabolites. It is historically accepted that one of the metabolites, fluoride, is the nephrotoxin, and that methoxyflurane nephrotoxicity is caused by plasma fluoride concentrations in excess of 50 microM. Sevoflurane also is metabolized to fluoride ion, and plasma concentrations may exceed 50 microM, yet sevoflurane nephrotoxicity has not been observed. It is possible that in situ renal metabolism of methoxyflurane, rather than hepatic metabolism, is a critical event leading to nephrotoxicity. We tested whether there was a metabolic basis for this hypothesis by examining the relative rates of methoxyflurane and sevoflurane defluorination by human kidney microsomes. METHODS: Microsomes and cytosol were prepared from kidneys of organ donors. Methoxyflurane and sevoflurane metabolism were measured with a fluoride selective electrode. Human cytochrome P450 isoforms contributing to renal anesthetic metabolism were identified by using isoform-selective inhibitors and by Western blot analysis of renal P450s in conjunction with metabolism by individual P450s expressed from a human hepatic complementary deoxyribonucleic acid library. RESULTS: Sevoflurane and methoxyflurane did undergo defluorination by human kidney microsomes. Fluoride production was dependent on time, reduced nicotinamide adenine dinucleotide phosphate, protein concentration, and anesthetic concentration. In seven human kidneys studied, enzymatic sevoflurane defluorination was minima, whereas methoxyflurane defluorination rates were substantially greater and exhibited large interindividual variability. Kidney cytosol did not catalyze anesthetic defluorination. Chemical inhibitors of the P450 isoforms 2E1, 2A6, and 3A diminished methoxyflurane and sevoflurane defluorination. Complementary deoxyribonucleic acid-expressed P450s 2E1, 2A6, and 3A4 catalyzed methoxyflurane and sevoflurane metabolism, in diminishing order of activity. These three P450s catalyzed the defluorination of methoxyflurane three to ten times faster than they did that of sevoflurane. Expressed P450 2B6 also catalyzed methoxyflurane defluorination, but 2B6 appeared not to contribute to renal microsomal methoxyflurane defluorination because the P450 2B6-selective inhibitor had no effect. CONCLUSIONS: Human kidney microsomes metabolize methoxyflurane, and to a much lesser extent sevoflurane, to fluoride ion. P450s 2E1 and/or 2A6 and P450 3A are implicated in the defluorination. If intrarenally generated fluoride or other metabolites are nephrotoxic, then renal metabolism may contribute to methoxyflurane nephrotoxicity. The relative paucity of renal sevoflurane defluorination may explain the absence of clinical sevoflurane nephrotoxicity to date, despite plasma fluoride concentrations that may exceed 50 microM. PMID- 7879939 TI - Effects of hypothermia, potassium , and verapamil on the action potential characteristics of canine cardiac Purkinje fibers. AB - BACKGROUND: Hypothermia may induce hypokalemia and increase intracellular Ca2+ by affecting serum K+ and Ca2+ fluxes across the cell membrane. These ionic alterations may significantly change the electrophysiologic characteristics of the cardiac action potential and may induce cardiac arrhythmias. The current study was undertaken to determine whether electrophysiologic changes in Purkinje fibers induced by hypothermia could be reversed by manipulating the extracellular K+ and transmembrane Ca2+ fluxes by Ca2+ channel blockade with verapamil. METHODS: A conventional microelectrode method was used to determine the effects of hypothermia (32 +/- 0.5 degrees C and 28 +/- 0.5 degrees C) and various external K+ concentrations ([K+]o) (2.3, 3.8, and 6.8 mM) on maximum diastolic potential, maximum rate of phase 0 depolarization (Vmax), and action potential duration (APD) at 50% (APD50) and at 95% (APD95) repolarization in isolated canine cardiac Purkinje fibers. To evaluate the contribution of the slow inward Ca2+ current to action potential changes in hypothermia, the experiments were repeated in the presence of the Ca(2+)-channel antagonist verapamil (1 microM). RESULTS: Variations of [K+]o induced the expected shifts in maximum diastolic potential, and hypothermia (28 degrees C) induced moderate depolarization, but only when [K+]o was > or = 3.9 mM (P < 0.05). Hypothermia decreased Vmax at all [K+]o studied (P < 0.05). Regardless of the temperature, Vmax was not affected by verapamil when [K+]o was < or = 3.9 mM, but at 6.8 mM [K+]o in hypothermia Vmax was significantly lower in the presence of verapamil. Hypothermia increased both the APD50 and the APD95. The effects of verapamil on APD were temperature and [K+]o dependent; between 37 degrees C and 28 degrees C with 2.3 mM [K+]o in the superfusate, verapamil did not affect APD. At 28 degrees C in the presence of verapamil, the APD50 and APD95 decreased only if the [K+]o was > or = 3.9 mM. CONCLUSIONS: Verapamil and K+ supplementation in hypothermia may exert an antiarrhythmic effect, primarily by reducing the dispersion fo prolonged APD. PMID- 7879941 TI - Comparative systemic toxicity of ropivacaine and bupivacaine in nonpregnant and pregnant ewes. AB - BACKGROUND: Ropivacaine is a new amide local anesthetic, having therapeutic properties similar to those of bupivacaine but with a wider margin of safety. Bupivacaine is probably the most commonly used drug in obstetric epidural analgesia, even though laboratory studies have suggested that pregnancy increases the cardiotoxicity of bupivacaine but not of other local anesthetics. The current study was designed to reevaluate, in a random and blinded fashion, the systemic toxicity of bupivacaine and ropivacaine in nonpregnant and pregnant sheep. METHODS: Chronically prepared nonpregnant and pregnant ewes were randomized to receive an intravenous infusion of ropivacaine or bupivacaine at a constant rate of 0.5 mg.kg-1.min-1 until circulatory collapse. The investigators were blinded to the identity of local anesthetic. Heart rate, arterial blood pressure, and cardiac rhythm were monitored throughout the study. Arterial blood samples were obtained before infusion and at the onset of toxic manifestations, which appeared in the following sequence: convulsions, hypotension, apnea, and circulatory collapse. Serum drug concentrations and protein binding were determined. Blood pH and gas tensions were measured. RESULTS: There were no significant differences between non-pregnant and pregnant animals in the doses or serum concentrations of either drug required to elicit toxic manifestations. In nonpregnant animals, similar doses and serum concentrations of ropivacaine and bupivacaine were associated with the onset of convulsions and circulatory collapse. In pregnant ewes, greater doses of ropivacaine as compared to bupivacaine were required to produce convulsions (7.5 +/- 0.5 vs. 5.0 +/- 0.6 mg.kg-1) and circulatory collapse (12.9 +/- 0.8 vs. 8.5 +/- 1.2 mg.kg-1). The corresponding serum concentrations of ropivacaine were similar to those of bupivacaine. Pregnancy did not affect the serum protein binding of either drug. The proportion of animals manifesting a malignant ventricular arrhythmia as the terminal event was similar among all groups. CONCLUSIONS: The systemic toxicity of ropivacaine or bupivacaine is not enhanced by gestation in sheep. This is in contrast to an earlier study in which the cardiotoxicity of bupivacaine was enhanced during ovine pregnancy. Greater doses of ropivacaine, as compared to bupivacaine, are needed to produce toxic manifestations in pregnant animals. PMID- 7879940 TI - Isoflurane and the pulmonary vascular pressure-flow relation at baseline and during sympathetic alpha- and beta-adrenoreceptor activation in chronically instrumented dogs. AB - BACKGROUND: The extent to which isoflurane anesthesia alters systemic vascular regulation has received considerable attention. In contrast, the pulmonary vascular effects of isoflurane have not been elucidated. Our initial objective was to investigate the net effect of isoflurane on the baseline left pulmonary vascular pressure-flow (LPQ) relation compared with values measured in the conscious state. In addition, we assessed the extent to which isoflurane alters the pulmonary vascular responses to sympathetic alpha- and beta-adrenoreceptor activation. METHODS: Twelve conditioned mongrel dogs were chronically instrumented to measure the LPQ relation. LPQ plots were generated by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure--left atrial pressure) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. LPQ plots were generated at baseline in the conscious and isoflurane-anesthetized states (n = 12). The pulmonary vascular dose-response relation to the sympathetic alpha-adrenoreceptor agonist phenylephrine also was investigated in conscious and isoflurane-anesthetized dogs (n = 6). Finally, after preconstriction with the thromboxane analogue U46619, the dose-response relation to the sympathetic beta-adrenoreceptor agonist isoproterenol was assessed in the conscious and isoflurane-anesthetized states (n = 8). RESULTS: Compared with values measured in the conscious state, isoflurane anesthesia had no net effect on the baseline LPQ relation. The magnitude of the pulmonary vasoconstrictor response to phenylephrine observed in conscious dogs was not altered during isoflurane anesthesia. In contrast, the pulmonary vasodilator response to isoproterenol was markedly potentiated (P < 0.01) during isoflurane anesthesia compared with that in the conscious state. CONCLUSIONS: These results indicate that isoflurane does not exert a net vasodilator influence on the pulmonary circulation at baseline. In contrast to the systemic circulation, the pulmonary vasoconstrictor response to sympathetic alpha adrenoreceptor activation is maintained during isoflurane anesthesia. Surprisingly, the pulmonary vasodilator response to sympathetic beta adrenoreceptor activation is actually potentiated during isoflurane. Thus, isoflurane anesthesia has differential effects on the canine pulmonary vascular responses to sympathetic alpha- and beta-adrenoreceptor activation. PMID- 7879942 TI - Analysis of drug interaction between intrathecal clonidine and MK-801 in peripheral neuropathic pain rat model. AB - BACKGROUND: Spinally delivered alpha 2-adrenoceptor agonists and N-methyl-D aspartate antagonists each have been shown to have actions attenuating the hyperesthesia in rat models of nerve injury pain. Using a fixed-dose analysis and an isobolographic paradigm, the spinal interaction between the alpha 2 adrenoceptor agonist clonidine and the N-methyl-D-aspartate antagonist MK-801 is characterized in a rat model of nerve injury-induced tactile hyperesthesia. METHODS: Male Sprague Dawley rats were anesthetized with halothane, and the left L5 and L6 spinal nerves were ligated (Chung model). After 7-10 days' recovery, a Polyethylene tubing catheter was implanted into the lumbar intrathecal space. After recovery from catheter implantations (5-7 days), intrathecal dose-response curves were established for the antihyperesthesia effects of clonidine (3, 6, 10, and 20 micrograms) and MK-801 (1, 3, 10, and 20 micrograms) alone to obtain the ED50 for each agent. In separate studies, three doses of clonidine (1, 3, and 10 micrograms) were injected mixed with one dose of MK-801 (1 microgram) for fixed dose analysis, and three doses of the two agents (2, 6, and 20 micrograms) were injected jointly in a fraction of the dose ratio 1:1 for isobolographic analysis. Thresholds for left hind paw withdrawal to von Frey hair application were assessed. RESULTS: Rats with nerve ligation showed a reliable tactile hyperesthesia (mechanical threshold 1-3 g vs. normal > 15 g). Intrathecal clonidine and MK-801 alone produced dose-dependent reductions of tactile hyperesthesia: ED50 9 micrograms and 10 micrograms, respectively. With the fixed dose analysis, the log dose-response curves showed a left shift that considerably exceeds the theoretical curve made by a simple sum of the effects of clonidine alone and with MK-801 (1 microgram). With the isobolographic analysis, the combination ED50 was found to be statistically less than the theoretical additive dose combination. Intrathecal atipamezole, an alpha 2 antagonist, reversed the effects of clonidine and the clonidine/MK-801 mixture but not MK-801 alone. The side effect of clonidine was sedation and urination and that of MK-801 was motor weakness at doses above 10 micrograms. These effects were considerably less severe in rats after equiactive doses in the combination group. CONCLUSIONS: The neuropathic pain is mediated by low-threshold mechanoreceptors, sympathetically dependent, and sensitive to both alpha 2 agonists and N-methyl-D-aspartate antagonists. Intrathecal clonidine may act to diminish sympathetic outflow, whereas MK-801 blocks the N-methyl-D-aspartate receptor that is associated with other spinal systems related to pain transmission mechanism. The two separate mechanisms may account for the powerful synergy observed in this study. Such combinations might be useful in neuropathic pain states to potentiate the antihyperpathic effects and to reduce the side effects of each agents. PMID- 7879943 TI - The membrane lipid cholesterol modulates anesthetic actions on a human brain ion channel. AB - BACKGROUND: Molecular theories of general anesthesia often are divided into two categories: (1) Anesthetics may bind specifically to proteins, such as ionic channels, and alter their function directly, and (2) anesthetics may alter the functions of integral membrane proteins indirectly through modification of the physical properties of the membrane. Recent studies have provided evidence that anesthetics can bind to proteins and modify their function directly, bringing into question the role of the membrane in anesthetic interactions. To reexamine the role of membrane lipids in anesthetic interactions, an experimental approach was used in which the membrane lipid composition could be systematically altered and the impact on anesthetic interactions with potential targets examined. METHODS: Sodium channels from human brain cortex were incorporated into planar lipid bilayers with increasing cholesterol content. The anesthetic suppression of these channels by pentobarbital was quantitatively examined by single channel measurements under voltage-clamp conditions. RESULTS: Changes in cholesterol content had no effect on measured channel properties in the absence of anesthetic. In the presence of pentobarbital, however, cholesterol inhibited anesthetic suppression of channel ionic currents, with 1.9% (weight/weight, corresponding to 3.5 mol%) cholesterol decreasing anesthetic suppression of sodium channels by half. CONCLUSIONS: These results support a critical role for the lipid membrane in some anesthetic actions and further indicate that differences in lipid composition must be considered in the interpretation of results when comparing the anesthetic potencies of potential targets in model systems. PMID- 7879945 TI - Charles Frederick Heywood. House surgeon at the ether demonstration. PMID- 7879944 TI - Buccal absorption of fentanyl is pH-dependent in dogs. AB - BACKGROUND: Analgesia and sedation have been achieved noninvasively by fentanyl administration through the oral and nasal mucosa. In theory, the transmucosal bioavailability and absorption of fentanyl could be improved by converting more fentanyl to the unionized form by adjusting the surrounding pH. The authors tested this hypothesis in dogs. METHODS: Under general anesthesia, each of six mongrel dogs was given fentanyl on repeated occasions, first intravenously (once), then by application to the buccal mucosa (six times). Buccal fentanyl administration was accomplished by placement of a pH-buffered solution of fentanyl into a specially constructed cell, which was clamped to the dog's buccal mucosa for 60 min. Fentanyl solutions with pHs of 6.6, 7.2, and 7.7 were studied to span a tenfold difference in the unionized fraction of fentanyl. Femoral arterial blood samples were sampled frequently and analyzed for fentanyl using a radioimmunoassay. Peak plasma concentration and the time of its occurrence for each buccal study were noted from the plasma concentration verses time profile. Terminal elimination half-life, bioavailability, and permeability coefficients were calculated using standard pharmacokinetic techniques. RESULTS: The variables peak plasma concentration, bioavailability, and permeability coefficient increased three- to fivefold as the pH of the fentanyl buccal solution increased and more fentanyl molecules became unionized. There was no difference in terminal elimination half-life after intravenous fentanyl (244 +/- 68 min) or buccal fentanyl administration (pH 7.7, 205 +/- 89 min; pH 7.2, 205 +/- 65 min; pH 6.6, 196 +/- 48 min). In all buccal studies regardless of pH, time to peak plasma concentration occurred within 10 min of removal of the fentanyl solutions from the buccal mucosa. CONCLUSIONS: The buccal absorption, bioavailability, and permeability of fentanyl are markedly increased as the pH of the fentanyl solution becomes more basic. Most likely, this is because of an increase in the fraction of unionized fentanyl. PMID- 7879946 TI - "In the present state of our knowledge". Early use of opioids in obstetrics. PMID- 7879947 TI - Fiberoptic evaluation of the difficult extubation. PMID- 7879948 TI - Transient bilateral vocal cord paralysis after insertion of a laryngeal mask airway. PMID- 7879949 TI - What is the incidence of perioperative transfusion-related acute lung injury? PMID- 7879950 TI - A simple, cost-effective method of preventing laryngoscope handle contamination. PMID- 7879951 TI - Universal adapter for endotracheal tubes revisited. PMID- 7879952 TI - A simple adaptation to the Olympus LF1 and LF2 flexible fiberoptic bronchoscopes for instillation of local anesthetic. PMID- 7879953 TI - Compartment syndrome after spinal surgery and use of the Codman frame. PMID- 7879955 TI - Femoral nerve injury may be related to abdominal wall retractor. PMID- 7879954 TI - Effect of pulmonary sympathetic blockade on bronchial responsiveness. PMID- 7879956 TI - Fiberoptic bronchoscopy in a patient requiring continuous positive airway pressure. PMID- 7879957 TI - Measurements of occlusion pressure during anesthesia with volatile anesthetics in humans. PMID- 7879958 TI - Arteriographic morphology and intracoronary thrombus in patients with unstable angina, non-Q wave myocardial infarction and stable angina pectoris. AB - Coronary artery lesions were compared in 71 patients with unstable angina, 15 patients with non-Q wave myocardial infarction (MI), and 40 patients with stable angina. In the unstable angina group, 29 patients had new-onset angina, 31 had crescendo angina, and 11 had rest angina. In a subgroup of patients with unstable angina, three-vessel disease was less frequently (P < 0.05) seen in patients with new-onset angina (10.3%) than in the patients with crescendo angina (51.6%) or rest angina (54.5%). An angina-producing artery could be identified in 59 patients with unstable angina, in 11 with non-Q wave MI, and in 30 with stable angina. Type II eccentric stenosis (asymmetric narrowing with narrow neck and overhanging irregular edges) was present in 31 patients (52.5%; P < 0.01) with unstable angina, in 7 (63.6%; P < 0.01) with non-Q wave MI, and in only 2 (6.7%) with stable angina. Abrupt occlusion of a vessel was observed in 7 patients (11.9%) with unstable angina and in 2 (18.2%) with non-Q wave MI. None of the patients with stable angina had this type of occlusion. In the group of unstable angina and non-Q wave MI, angiographic evidence of intracoronary thrombi was present in 16 (27.1%) and 3 patients (27.3%), respectively, but in stable angina in only 1 patient (3.3%; P < 0.05). Intracoronary thrombi were most frequently found in rest angina (88%; P < 0.001) and crescendo angina (33.3%; P < 0.01) compared with new-onset angina (3.7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879959 TI - Classification of congenital arterial and venous vascular malformations. AB - Arterial and venous vascular malformations due to congenital abnormalities rarely occur in the daily practice of vascular surgeons. These malformations represent a heterogeneous group of isolated or multiple congenital abnormalities, sometimes associated with complex congenital syndromes. Correct recognition and classification of these rare abnormalities may sometimes be difficult. No systematic classification of arterial and/or venous vascular malformations due to congenital abnormalities is currently available. On the basis of embryologic and pathophysiologic considerations, a rational and simple classification of arterial and venous vascular malformations due to congenital abnormalities can be performed. This contribution presents an appropriate classification of clinically important arterial and venous vascular malformations due to congenital abnormalities. PMID- 7879960 TI - Direct in vivo visualization of right cardiac anatomy by fiberoptic endoscopy. Hemodynamic effects and image validation. AB - The authors tested the ability of a balloon-tipped fiberoptic endoscope to accurately visualize and identify right-heart anatomy in 7 anesthetized dogs. A 3.6-mm-diameter fiberoptic endoscope with a latex balloon covering the distal tip was inserted into the right atrium, where the balloon was inflated with air in 5 mL increments. Heart rate did not show changes. Mean arterial pressure and cardiac output started to show significant decreases with a balloon volume at 25 and 20 mL, respectively (n = 7). Visual image quality was excellent with a balloon volume of 10 mL or greater. With a balloon volume of 7-10 mL, the visual field was 15-20 mm in diameter. Right-heart anatomy including the right free wall, ostium of the coronary sinus, atrioventricular node area, tricuspid valve, right ventricular structures, and pulmonary arteries was clearly and accurately identified. Additionally, spatial relationships among these structures could be established. Furthermore, there was an excellent concordance between endoscopically observed images and postmortem findings. In conclusion, balloon tipped fiberoptic endoscopy can accurately visualize normal intracardiac structures with no or minimal hemodynamic compromise. PMID- 7879961 TI - Ankle/arm pressure index in asymptomatic middle-aged males: an independent predictor of ten-year coronary heart disease mortality. AB - PURPOSE OF THE STUDY: to evaluate the predictive power of a reduced ankle/brachial pressure index (ABPI) (< or = .90) in an asymptomatic middle-aged male working population free of coronary heart disease. MATERIALS AND METHODS: 2023 subjects forty to fifty-five years old were screened at their work place. Standard techniques were used. Blood was drawn in the fasting state. Ankle and brachial blood pressures were measured by Doppler signals and all measures were done by one observer, duly trained in epidemiologic methodology. RESULTS: in univariate analysis, an ABPI < or = .90 was significantly associated with age, total serum cholesterol, body mass index, smoking, and awareness of diabetes. In multivariate analysis, it was associated with awareness of diabetes, age, Ln triglycerides (P = .073), and smoking (P = .088). Relative risks for reduced versus normal ABPI are 2.77 (P = .010), 4.16 (P = .011) and 4.97 (P = .006) for ten-year all causes, cardiovascular, and coronary mortality, respectively. In a multiple logistic regression analysis, the following variables were significant independent predictors of coronary mortality: smoking (odds ratio [OR] = 4.84), reduced ABPI (OR = 3.63), and low density lipoprotein cholesterol (OR for 1 SD = 1.69). Reduced ABPI is also an independent predictor of cardiovascular mortality. CONCLUSION: a reduced ABPI is an independent risk factor for coronary and cardiovascular mortality in asymptomatic middle-aged Belgian males. PMID- 7879962 TI - Plasma catecholamines, thrombocyte alpha 2- and lymphocyte beta 2-adrenoceptor densities in hypertensive patients with low or normal plasma renin concentrations. AB - The sympathetic nervous system is unique in the regulation of plasma renin, for it can stimulate or suppress renin release by activation of either renal beta- or alpha 2-adrenoceptors. The authors studied plasma renin concentration (PRC), noradrenalin and adrenalin levels in plasma, and the densities of lymphocyte beta 2-adrenoceptors and thrombocyte alpha 2-adrenoceptors in 25 hypertensive patients with either normal (11-40 mU/L; n = 9) or low PRC (0-10 mU/L; n = 14). There were no differences in plasma catecholamine levels and adrenoceptor densities between the two patient groups. A positive correlation (r = 0.66; P < 0.005) between beta 2-adrenoceptor density and PRC in the patient group with low PRC, and a negative correlation (r = -0.72; P < 0.01) between alpha 2-adrenoceptor density and plasma renin in patients with normal PRC were found. They conclude that adrenoceptor densities on blood elements and plasma catecholamines do not differ in low and normal renin hypertension. The significant correlations between adrenoceptor densities and PRCs may indicate that adrenoceptors on blood elements mirror adrenoceptor densities in the kidney and that tonic suppression of renin release through alpha 2-adrenoceptors is preserved in hypertensive patients with normal plasma renin levels. PMID- 7879963 TI - Do hydrophilic guidewires affect the technical success rates of percutaneous angioplasty? AB - To determine whether the use of hydrophilic guidewires has influenced the success of peripheral percutaneous transluminal angioplasty (PTA), the results of PTA performed before and after the introduction of such guidewires (end of 1989) were analyzed. Before hydrophilic guidewires became generally available, the technical success rates for iliac stenosis PTA were 96%, for femoral stenosis PTA 84%, and for femoral occlusion 78%. After the introduction of hydrophilic guidewires, technical success rates were 100% (NS), 97% (P = 0.018), and 97% (P = 0.011), respectively. A prospective study of 33 patients randomly selected for PTA of femoropopliteal occlusion using either conventional or hydrophilic guidewires was performed. In this group, the technical success rate was 14/15 in the hydrophilic group, and 18/18 in the conventional group (NS). Since the introduction of hydrophilic guidewires, the technical success rates of PTA have improved and are now approaching 100%. PMID- 7879964 TI - Direct connection between the coronary arteries in the human heart. Intercoronary arterial continuity. AB - Seven cases of intercoronary arterial continuity are described, which were obtained from a study of 100 human hearts in individuals with an average age (+/- standard deviation) of 61.09 years (+/- 21.96). The methods used in the study were postmortem coronary angiography and dissection. In those cases in which intercoronary continuity was found, a histologic study was performed on the connecting vessel, together with the distal portions of the interconnected arteries. Of the 7 cases observed, 5 showed continuity between the anterior and posterior interventricular arteries, in the distal portion of the posterior interventricular groove. The remaining 2 cases showed continuity between the distal portions of the right coronary artery and the circumflex artery, occurring in the posterior auriculoventricular groove. In all cases, continuity was by means of a single vessel in epicardial position, with a diameter similar to that of the terminal portions of the interconnected arteries. The histologic structure of the connecting vessel had the characteristics of a normal arterial wall, so the authors conclude, therefore, that in these cases of intercoronary continuity reported in adult hearts, there is a persistence of the type of coronary circulation observed in the fetus. PMID- 7879965 TI - Connective tissue accumulation in the muscle layer in normal and varicose saphenous veins. AB - Varicose veins alternate areas of phlebosclerosis and hypertrophy of the vein wall. In this study, samples of long saphenous veins obtained from patients submitted for aortocoronary saphenous vein graft or for surgical resection of varicose saphenous veins were examined. Histologic changes in the intima, muscle, and adventitial layers were quantified. Thicknesses of the venous wall layers were obtained by linear measurements, and the volumetric density of the connective tissue in the muscle layer was determined by point counting. The muscle layer thickness was 300 +/- 13 and 581 +/- 25 microns in normal and varicose veins, respectively. A more severe connective tissue accumulation within the muscle bundles was found in the varicose condition. The volumetric density of the connective tissue in the circular muscle layer (CmC/MmC) showed also a marked difference between varicose (0.67 +/- 0.08) and normal veins (0.43 +/- 0.02), P < 0.05. The authors suggest that the varicose condition is associated with a connective tissue uniform accumulation among muscle cells in the circular muscle layer. PMID- 7879966 TI - Two concurrent spinal dural arteriovenous fistulae in a patient with rapidly progressive myelopathy. A case report. AB - A rare case of two separate spinal dural arteriovenous fistulae (DAVFs) occurring concurrently in a patient with a rapidly progressive myelopathy is reported. Although concurrent spinal DAVFs may be "well known," their occurrence has been only anecdotally reported. To the authors' knowledge, this well documented case of a presumably rare variant of spinal DAVFs is the first to appear in the literature and is instructive for reconsidering approaches to optimal diagnosis and evaluation of posttherapeutic efficacy of these lesions. PMID- 7879967 TI - Transvenous permanent left ventricular pacing. A case report. AB - This case report presents a patient who inadvertently received transvenous permanent left ventricular pacing through an unexpected atrial septal defect. This lead malpositioning was proved by two-dimensional and transesophageal echocardiography. The abnormal pattern of electric activation was demonstrated by radionuclide phase image analysis. He has been followed up for a total of forty three months with antiplatelet therapy and has been free from systemic embolic phenomena. A simple and readily available method that could lead to early recognition of lead malpositioning is reiterated and the various causes, methods of detection, and prognosis of left ventricular pacing are discussed. PMID- 7879968 TI - Multiple aneurysms of the cephalic vein. A case report. AB - An uncommon case of multiple multiform venous aneurysms of the cephalic vein of a seventeen-year-old girl is presented. The case is discussed in the light of the related literature. PMID- 7879969 TI - Effect of sample handling on measurement of plasma glucose and blood lactate concentrations in horses before and after exercise. AB - Collection of a satisfactory blood sample requires special procedures to prevent changes in glucose and lactate content after the sample has been obtained. Changes in measured plasma glucose and blood lactate concentrations attributable to anticoagulants and storage procedures, respectively, were examined in blood samples obtained from horses at rest and after exercise. To evaluate the effect of anticoagulants on measured plasma glucose concentration, blood was preserved with either sodium fluoride/potassium oxalate or lithium heparin. Measured plasma glucose concentration in blood obtained at rest and after exercise was 6 and 10% lower (P = 0.0038), respectively, when blood was preserved with fluoride/oxalate, compared with heparin. The erythrocyte volume in the blood sample was 15% smaller (P = 0.0001) in samples preserved with fluoride/oxalate, indicating a movement of water out of erythrocytes in the blood sample mixed with that anticoagulant. To evaluate the effect of storage procedure on measured blood lactate concentration, part of the blood sample was immediately deproteinized for blood lactate analysis, and the remaining blood was maintained for 30 and 60 minutes at either 0 or 22 C before deproteinization. When blood samples were maintained at 0 C prior to deproteinization, there was no difference in blood lactate concentration, regardless of the incubation time, compared with that in samples immediately deproteinized. Blood lactate concentration was greater (P < 0.01) in samples maintained at 22 C, compared with that in samples immediately deproteinized, and with that in equivalent samples maintained at 0 C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879970 TI - Effect of prior lavage on bronchoalveolar lavage fluid cell population of lavaged and unlavaged lung segments in horses. AB - Bronchoalveolar lavage (BAL) was performed on 16 horses to determine whether it caused local or diffuse inflammation in the lungs. In 7 horses, BAL was performed in both lungs twice, 48 hours apart. Although total cell counts of the BAL samples did not change significantly, there were increased numbers and percentage of neutrophils in the second lavage fluid samples. In 5 horses, BAL was performed in 1 lung and repeated 48 hours later in the same lung and in the corresponding airway in the contralateral lung. The absolute cell count and percentage of neutrophils were significantly (P = < 0.05) increased in the second sample from the lung that was lavaged twice. In 4 horses, BAL was performed in 1 lung and 48 hours later, repeated in an adjacent airway to the first BAL site, and in the corresponding airway in the contralateral lung. Significant differences were not detected in the total or differential cell counts of the BAL fluid recovered at any time, except for an increase in neutrophil percentage in the second sample in the contralateral lung. The increased neutrophil percentage values were within the range of normal for healthy horses. Results of the study suggested that, in horses, BAL induces a localized pulmonary neutrophil influx that persists at least 48 hours and is characterized by a relative and absolute increase in the number of neutrophils in the lavage fluids. and has been shown to be a safe technique with cytologic results that correlate well with histopathologic lesions in horses. Subsequently the technique has been used to collect large numbers of pulmonary cells for study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879971 TI - Three-dimensional sonographic imaging of the equine superficial digital flexor tendon. AB - In a feasability study, a technique for constructing 3-dimensional sonographic images of the superficial digital flexor tendon (SDFT) was established in 6 clinically normal horses and applied to 7 horses with injured SDFT. Two dimensional B-mode sonographic images were recorded on videotape as the sonographic transducer was manually moved along the palmar aspect of the metacarpal region. Selected videofields were digitized, and 3-dimensional images were constructed, using a computer work station and dedicated software program. The 3-dimensional images were of high quality and presented qualitative clinical information in unique fashion. Indication of the extent of SDFT injuries was excellent. Such 3-dimensional images would be especially useful in explaining to owners and trainers the importance of the injury to their horse and would have a role in monitoring tendon healing and in the assessment of various treatments. PMID- 7879972 TI - Polymerase chain reaction for detection of Borrelia coriaceae, putative agent of epizootic bovine abortion. AB - The nucleotide sequence of a chromosomally encoded antigen-expressing gene of Borrelia coriaceae was determined and used as a target for the polymerase chain reaction (PCR). Two primer sets were designed specifying the amplification of 269 and 701-bp DNA fragments. Primer set I, producing the short amplicon, was tenfold more sensitive than primer set II. As little as 10 fg of purified B coriaceae DNA could consistently be detected. The PCR assays, containing controlled numbers of whole spirochetes, allowed detectable amplification of 2 to 10 organisms. An internal, nonradioactively labeled gene-specific probe verified specificity of the PCR amplicons. Neither primer set cross-reacted with other related spirochetes. This PCR assay was adapted and found suitable for identification of B coriaceae in biological samples, such as blood and thymus. Evidence for presence of B coriaceae in biological samples was not found in tissue samples obtained from experimentally infected cows and their fetuses. These data failed to establish a definite association between B coriaceae and epizootic bovine abortion. PMID- 7879973 TI - Enteric pathogens in intensively reared veal calves. AB - Observations were made on development of diarrhea in special-fed calves (n = 460) on 8 commercial facilities during 2 successive 16-week production cycles at weeks 0, 2, 4, 8, 12, and 16. A total of 23% were affected, with peak number of calves with diarrhea observed at week 0. Suspected enteropathogens were identified in 86% of these calves, most commonly cryptosporidia, coronavirus, and rotavirus. Identified potential zoonotic pathogens included Giardia and Salmonella spp and verotoxigenic Escherichia coli. Noncytopathic bovine viral diarrhea virus was isolated from 6 calves that had repeated bouts of illness. Only 22% of calves entering the veal facilities had adequate transfer of passive immunity. At week 0, serum IgG concentration in calves that subsequently died or had diarrhea was lower (P < 0.001) than that in healthy calves. All calves that died (n = 6) during the first 4 weeks of production had complete failure of transfer of passive immunity. PMID- 7879974 TI - Effect of early lactation milk yield on reproductive disorders in dairy cows. AB - Association between individual cumulative milk yield and various reproductive disorders in 56,772 Finnish Ayrshire cows belonging to 5,912 herds in 80 communities was studied. All cows delivered calves between September 1985 and September 1986. Five logistic regression models were fitted, 1 for each outcome disorder of interest: early metritis, late metritis, silent heat, ovarian cyst, and other infertility. Cumulative individual 37-day milk yield was used in the early metritis model, and cumulative individual 60-day milk yield was used in the other models, on the basis of median days in milk when these disorders developed. Cumulative 305-day herd milk yield, parity, calving season, presence or absence of other disorders, and community were also included in the models. Point estimates from the models represented odds ratios for the likelihood of having the outcome disorder. Lactational incidence risks for the 5 reproductive disorders studied were: early metritis (2.4%), late metritis (1.1%), silent heat (5.4%), ovarian cyst (6.6%), and other infertility (2.1%). The risk of early metritis decreased with increasing 37-day milk yield. The risk of silent heat, ovarian cyst, and other infertility increased with increasing 60-day milk yield; 60-day milk yield had no effect on late metritis. The 305-day herd milk yield increased the risk of early metritis, ovarian cyst, and other infertility; it had no effect on late metritis or silent heat. Parity had an effect on all disorders, except late metritis. Cows that delivered calves during the colder, darker seasons of the year had a higher risk of reproductive disorders than did those that delivered calves at other times of the year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879976 TI - Clinical, hematologic, and biochemical findings in dogs after induction of shock by injection of heartworm extract. AB - A crude, whole-body extract of female or male heartworms was injected IV into 28 dogs with and 22 dogs without heartworm (HW) infection. The female HW extract caused shock in 22 of 24 dogs with and 12 of 20 dogs without HW infection. The male HW extract induced shock in 4 of 4 dogs with and 1 of 2 dogs without HW infection. Prevalence of shock caused by female HW extract was significantly (P < 0.05) higher in dogs with than without HW infection; shock developed 5 to 30 minutes after HW injection. These signs were observed: marked decrease in blood pressure; collapse (initial collapse); paleness of mucous membranes; weak heart sounds; dyspnea; skin coldness; intestinal hyperperistalsis, and defecation; increases in RBC count, serum total protein concentration, serum osmolality, serum Na and blood glucose concentrations; and decreases in neutrophil, eosinophil, and platelet counts. Alanine transaminase, alkaline phosphatase, and lactate dehydrogenase activities increased substantially from the time of initial collapse to 24 hours after HW injection. Of 39 dogs with shock, 29 recovered from initial collapse, but 5 of the 29 subsequently collapsed again (secondary collapse), with bloody diarrhea followed by death. Of these 39 dogs, 6 died during initial collapse without bloody diarrhea, and 4 were euthanatized during initial collapse. It was confirmed that HW extract had, in fact, induced shock. These clinical, hematologic, and biochemical findings were fundamentally similar to those associated with shock resulting from administration of drugs, such as diethylcarbamazine and milbemycin D, in microfilaremic dogs with HW infection. PMID- 7879975 TI - Experimentally induced infection with bluetongue virus serotype 11 in cows. AB - The consequences of inoculation of bluetongue virus (BTV) serotype 11 into 16 susceptible cows either at the time of breeding or at specified stages of pregnancy were studied. The cows were free of BTV or epizootic hemorrhagic disease virus, and none had antibodies to BTV before virus inoculation. A group of 4 cows was mated naturally to a bull reported to shed BTV-11 (CO75B300 strain) in the semen. The bull was suspected of infecting cows at mating with BTV-11, which subsequently transplacentally infected the developing fetuses and induced persistently infected and congenitally malformed progeny. Two groups of 4 pregnant cows were inoculated with an insect-derived strain of BTV-11 (CO75B300), one group by direct deposit into the uterus at estrus, the other, by intradermal and SC administrations. A 90-day fetus was inoculated in utero with virus from the same pool. Four pregnant cows were inoculated with sheep blood-passaged virus of the same BTV-11 strain (CO75B300) by intradermal and SC routes. Three cows were inoculated with BTV-free suspending fluids and ovine erythrocytes by the intrauterine and intradermal-SC routes and were used as in-contact controls. Infection with insect-derived BTV-11 was confirmed in 3 cows of 1 group by virus isolation and by detection of serum antibodies. The 4 cows inoculated with sheep blood suspension of BTV-11 developed viremia and produced antibodies to the virus. None of the cattle had clinical signs of bluetongue, other than 2 cows that had a slight rectal temperature increase on postinoculation day 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879977 TI - Blood coagulopathy in dogs with shock induced by injection of heartworm extract. AB - A crude, whole-body extract of female heartworms was administered IV to 10 dogs with and 13 dogs without heartworm (HW) infection. Shock developed in 8 of 10 infected dogs and 11 of 13 non-infected dogs, and blood coagulopathy was observed in 12 of 19 dogs with shock. Prevalence and severity of blood coagulopathy were proportionate to prevalence and severity of shock. Platelet count decreased in all dogs with shock with or without blood coagulopathy; thus, the decrease in platelet count might be related to shock. In 4 dogs, activated partial thromboplastin time (APTT) was prolonged--192.0 seconds at 30 minutes after HW injection--and prothrombin time (PT) was increased--13.8 seconds at initial collapse. In 8 dogs, APTT was increased--200 seconds for 2 hours after HW injection--and PT was increased--200 seconds at 30 minutes after the injection. The APTT prolongation might have been caused mainly by decreases in activities of factors VIII, IX, XI, and XII of the intrinsic blood coagulation pathway. In dogs with severely prolonged PT, plasma fibrinogen concentration and factor II activity decreased slightly. Prolonged PT was corrected in vitro by addition of normal plasma at high concentration (> 80%), but prolonged APTT could not be corrected in vitro by addition of 80% normal plasma. Serum fibrin degradation products concentration was < 10 micrograms/ml, and soluble fibrin monomer complex was negative in all dogs. Thrombi were not found in blood vessels of any organ at necropsy and after histologic study. Therefore, it was suggested that blood coagulopathy resulting from inhibition of coagulation factor activities might develop in shock induced by HW extract. PMID- 7879978 TI - Functional and structural changes of porcine alveolar macrophages induced by sublytic doses of a heat-labile, hemolytic, cytotoxic substance produced by Actinobacillus pleuropneumoniae. AB - Alterations in the size and functions of porcine alveolar macrophages exposed to sublytic amounts of heat-labile, hemolytic cytotoxin produced by Actinobacillus pleuropneumoniae (App) serotype 1, strain HS54 into the culture medium were studied in vitro. Alveolar macrophages were sensitive to the cytotoxin; treatment of the macrophages with low concentrations of cytotoxin (0.016 hemolytic unit) resulted in severe, irreversible cell swelling. However, high doses of cytotoxin (2.0 hemolytic units) were required to cause substantial cell death, as indicated by the influx of propidium iodide into and release of lactate dehydrogenase from cells. Macrophages exposed to low, sublytic doses of cytotoxin failed to migrate toward chemoattractant, were unable to attach to glass, and failed to phagocytize optimally opsonized erythrocytes. Macrophages already attached to glass surfaces detached when exposed to sublytic doses of cytotoxin. The swelling and impairment of functions of alveolar macrophages observed in this study could not be attributed to endotoxic effects, because heat treatment of the cytotoxin preparation for 60 minutes at 60 C resulted in complete loss of cytotoxicity. We conclude that sublytic doses of heat-labile, hemolytic cytotoxic substances produced by App depress alveolar macrophage function at concentrations likely to develop in association with acute pulmonary infection with App. The Apx (A pleuropneumoniae Rtx toxins) exotoxins secreted by the bacteria into culture medium were considered responsible for the toxic activity of the cytotoxin preparation. The Apx of the App field strain used in this study were likely to be similar to those of serotype-1 reference strain (S4707). Analysis by use of DNA DNA hybridization indicated that genomic DNA of the field strain contained sequences similar to those encoding structural protein of ApxI (apxIA) and ApxII (apxIIA) of the serotype-1 reference strain. Therefore, Apx produced by the field strain of App used in this study are likely to be of similar pathogenic importance worldwide. PMID- 7879979 TI - Ferula communis variety brevifolia intoxication of sheep. AB - Sheep given powdered Ferula communis variety brevifolia at dosage of 2.5 g/kg of body weight/d for 15 days developed classical clinical signs of intoxication: anorexia, somnolence, apparent weakness, and hemorrhage. Marked reduction of vitamin K-dependent coagulation factors and prolongation of prothrombin time and activated partial thromboplastin time were consistent with presence of ferulenol, a toxic coumarinic factor in the plant. Changes induced in the coagulation system developed by the second day of plant administration and were normal within 4 days after dosing was stopped. There was no evidence of primary liver damage or platelet malfunction. Of 6 intoxicated sheep, 2 died with only minimal evidence of hemorrhage. PMID- 7879980 TI - Plasma ferulenol concentration and activity of clotting factors in sheep with Ferula communis variety brevifolia intoxication. AB - Dynamics of plasma ferulenol concentration and its effect on the vitamin K dependent coagulation factors, prothrombin time (PT), and activated partial thromboplastin time (APTT) were determined in 4 sheep intoxicated individually with 600 g of powdered Ferula communis variety brevifolia (FCb) given in 8 doses at intervals of 6 hours. Ferulenol was detected in the plasma of all sheep at initial blood sample collection, 6 hours after the first dose of approximately 75 g of FCb was placed in the rumen. The last observed peak of approximately 20 micrograms/ml was detected at about 12 hours after the last of 8 doses, and the mean concentration then decreased to < 1 microgram/ml during the next 70 hours. Maximal concentration of ferulenol and time for plasma clearance varied with individual sheep. The PT increased steadily to a maximum of 6 times normal about 70 hours after the last peak plasma ferulenol concentration and about 80 hours after FCb administration was stopped. The PT then returned to almost normal (ratio of 1.12) from the maximum (ratio of 6.12) within approximately 5 days. The APTT results generally paralleled the PT results, but the change was not as marked. Maximal PT and APTT ratios were animal-dependent and not always related to plasma ferulenol concentration. The activity of all the vitamin K-dependent coagulation factors was depressed, but the variations were unique to each factor. Factor V, a vitamin K-independent coagulation factor actually had a brief period of increased plasma activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879981 TI - Effect of phenylephrine on hemodynamics and splenic dimensions in horses. AB - Pharmacologically induced splenic contraction might be useful during certain medical or surgical procedures in horses. The effects of phenylephrine, an alpha 1-adrenergic receptor agonist, on hemodynamic function and splenic dimensions were examined in 6 healthy adult horses. Phenylephrine infusion (1, 3, or 6 micrograms/kg of body weight/min for 15 minutes) resulted in a dose-related increase in mean pulmonary artery pressure; right atrial pressure; systolic, mean, and diastolic arterial pressures; and packed cell volume (P = 0.0001). Concurrent decreases in heart rate and specific cardiac output (P = 0.0001) were detected, but stroke volume did not vary significantly. The rate-pressure product was increased only at the highest phenylephrine dosage (P = 0.012). Bradycardia was observed at all dosages during drug infusion, and second-degree atrioventricular block was detected in 88% of horses during infusion. Phenylephrine administration caused dose-dependent splenic contraction, as detected by ultrasonographic measurements of splenic area and thickness (P = 0.0001). At the 3- and 6-micrograms/kg/min infusion rates, splenic area was reduced to 28 and 17% of baseline measurement, respectively. Splenic dimensions had returned to baseline values by 35 minutes after the end of infusion. Infusion of phenylephrine at a dosage of 3 micrograms/kg/min for 15 minutes can be used to induce splenic contraction in horses. PMID- 7879982 TI - Comparison of maturation of drug-metabolizing enzymes in calves with functioning or nonfunctioning rumen. AB - Drug-metabolizing enzyme activities were measured in livers from calves fed commercial milk replacer (nonfunctioning rumen [veal]), and those fed milk replacer supplemented with whole grain and hay from the first week of age (functioning rumen [ruminating calves]). After birth, cytochrome P450 and its NADPH-dependent reductase activities remained unchanged in veal calves; in ruminating calves they increased almost 50%. Cytochrome P450-mediated reactions, such as aniline hydroxylase activity, tripled in ruminating calves, but remained unchanged in veal calves. In both groups of calves, coumarin hydroxylase and 7 ethoxycoumarin 0-deethylase activities increased after birth, but maturation rates and activity values in ruminating calves were considerably greater than those of veal calves. The aminopyrine N-demethylase activity for veal calves was equal to that of calves with functioning rumen. Uridine diphosphoglucuronic acid glucuronyl transferase and glutathione-S-transferase activities also were higher in calves with functioning rumen than in veal calves. This increased activity in calves with functioning rumen probably represents a response to environmental exposure to xenobiotics. Compared with rumen-functional calves, bob veal (0 to 3 weeks old) and fancy veal (15 to 19 weeks old) calves fed commercial milk replacer have a significantly (P = 0.05) diminished capacity for metabolizing drugs and other xenobiotics. From a regulatory perspective, the variance in drug metabolizing enzyme activities within these different market classes of calves suggests that specific studies designed to determine drug residue-depletion times in veal calves may be needed. PMID- 7879983 TI - Comparison of body surface area-based and weight-based dosage protocols for doxorubicin administration in dogs. AB - Pharmacokinetics and toxicity of a single dose of doxorubicin, at dosages of 30 mg/m2 of body surface area and 1 mg/kg of body weight, were compared in 17 dogs. Effects of doxorubicin on complete blood cell count, platelet count, and the dogs' clinical condition were evaluated for 14 days. Cluster analysis, on the basis of clinical signs of doxorubicin toxicosis at the 30-mg/m2 dosage, revealed that 6 of 7 small dogs (< or = 10 kg) became ill, whereas 7 of 10 large dogs (> 10 kg) remained clinically normal. Small dogs that received doxorubicin at a dosage of 30 mg/m2 had higher peak plasma concentrations, greater area under the curve for plasma drug concentration vs time, longer drug elimination half-lives, greater volumes of distribution, and more clinical signs of toxicosis than had large dogs (P < or = 0.05). Five of 9 small dogs that received doxorubicin at a dosage of 30 mg/m2 developed severe myelosuppression (< 1 x 10(3) granulocytes/microliters). In contrast to the toxicoses with body surface area based dosing, myelosuppression was not induced in small dogs that received doxorubicin at a dosage of 1 mg/kg. In small and large dogs given doxorubicin at a dosage of 1 mg/kg, pharmacokinetic characteristics and clinical signs of toxicosis were similar. Mean WBC counts and granulocyte counts for all dogs were lower on day 7 with 30 mg of doxorubicin/m2 (n = 17), compared with that for 1 mg of doxorubicin/kg (n = 14; P < or = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879984 TI - Coat color darkening in a dog in response to a potent melanotropic peptide. AB - Analogues of a melanocyte-stimulating hormone (alpha-MSH) have been documented to be effective in inducing integumental melanogenesis in several species. These melanotropin analogues are more potent than the natural hormone and have prolonged biological activity, without apparent teratogenic or other toxic effects, at least in rodents. In a pilot study, a cyclic alpha-MSH analogue, Ac [Nle4, Asp5, D-Phe7, Lys10] alpha-MSH4-10-NH2, was administered SC to a dog at a dose of 1 mg of analogue in 1 ml of 0.9% NaCl for 3 weeks, without noticeable adverse effects. There was gradual and extensive darkening of the coat, which originally was predominantly tan, with tips of black. Initially, the darkening involved face and extremities, then gradually expanded to include the trunk and tail hair. Visual pigmentation peaked approximately 2 months after injections were completed. As new hair growth continued subsequent to the injections, the original tan color appeared at the proximal end of the hair shaft, leaving a dark terminal band on all affected hairs. These observations clearly indicated that follicular melanogenesis can be induced in dogs by treatment with a melanotropic peptide. PMID- 7879985 TI - Pharmacokinetics and short-term clinicopathologic changes after intravenous administration of a high dose of methimazole in dogs. AB - A bolus dose of methimazole (MMI) was administered IV over 1 minute to 5 healthy adult dogs at a dosage (40 mg/kg of body weight) known to impart protection against cisplatin-induced renal disease. Blood and urine samples for pharmacokinetic analysis were collected over a 24-hour period. Physical examination, CBC, determination of serum thyroid hormone concentrations, and serum biochemistry analysis were performed over a 10-day period to evaluate short term toxicoses. At this dosage, MMI appears to be safe and well tolerated in dogs; only 1 of the 5 dogs had mild and transient increases in serum activity of hepatic enzymes. In addition, MMI did not alter serum thyroid hormone concentrations. Half-life of 8.82 hours and mean residence time of 12.18 hours were determined for MMI. Renal clearance of native MMI, along with sulfate and glucuronide conjugates, represented only 20% of total systemic clearance. Results of this study provide further information concerning clinical use of MMI in dogs and may contribute to better understanding of the mechanism of MMI protection against chemically induced nephrotoxicosis. PMID- 7879986 TI - Whole-blood platelet aggregation, buccal mucosa bleeding time, and serum cephalothin concentration in dogs receiving a presurgical antibiotic protocol. AB - Whole-blood platelet aggregation (using the impedance method) and adenosine triphosphate (ATP) release, buccal mucosal bleeding time (BT), and serum cephalothin concentration were measured in 21 adult female Beagles before (PRE) and 1 hour (1 HR) after IV administration of cephalothin (22 mg/kg). A second injection of cephalothin (22 mg/kg) was given 3 hours after the first, and blood samples were obtained 1 hour (4 HR, 4 hours after the first injection) and 3 hours (6 HR, 6 hours after the first injection) after the second injection. Samples of jugular blood were obtained from each dog, using citrate as an anticoagulant. A platelet count was obtained for each sample. Platelet aggregation and ATP released from the aggregating platelets were measured within 1 hour of sample collection, using a whole-blood aggregometer. Adenosine diphosphate (ADP) and collagen were used as aggregating agents. Aggregation was measured over 6 minutes for each aggregating agent; ATP release in response to collagen, but not to ADP, was measured over the same period. For 1 HR samples, there was a significant (P < 0.01) reduction from PRE values in the ability of platelets to aggregate in response to ADP. Bleeding time was determined, using a published procedure, with each dog as its own control. Bleeding time during the same period was found to be significantly increased over PRE values for 1 HR (P < 0.01) and 6 HR (P < 0.02) samples. There was no significant difference between BT for 1 HR and 4 HR samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879987 TI - Investigation of oxygen-derived free radical generation in cancellous bone specimens obtained from dogs. AB - Generation of free radicals and the ability of various antioxidants to attenuate radical production in freshly procured cancellous bone specimens was investigated, using spin-trapping and electron spin resonance (ESR) techniques. Seven core cancellous bone specimens, 10 mm long and 7.9 mm in diameter, were obtained using aseptic technique, from the proximal portion of the humerus of 9 adult mixed-breed dogs. One core cancellous bone specimen from each dog was incubated in spin trap alpha-phenyl-N-tert-butylnitrone in Eagle's minimum essential medium and served as a control. The other 6 specimens from each dog were incubated in alpha-phenyl-N-tert-butylnitrone/Eagle's minimum essential medium plus 1 of the following antioxidants: superoxide dismutase, catalase, superoxide dismutase/catalase, indomethacin, allopurinol, or deferoxamine mesylate. All specimens were incubated at 26 C for 90 minutes, then frozen at -20 C until they were prepared for analysis by ESR spectroscopy. Each specimen was thawed, homogenized, and extracted in a low-dielectric organic solvent prior to obtaining an ESR spectrum which was analyzed for hyperfine splitting constants to identify radicals. Each first-derivative spectrum was digitally double-integrated to obtain an area: these areas were used to compare intensities of the spin. For each treatment group, the areas from the treated specimens were compared with the areas from the control specimens, using a paired t-test. Significance was accepted at P < or = 0.05. Spin adducts were detected in all cancellous bone specimens. Specimens incubated in deferoxamine (P = 0.0017) and superoxide dismutase/catalase (P = 0.0452) had significantly smaller areas than did control specimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879988 TI - Rate of change of QT interval in response to a sudden change in the heart rate in dogs. AB - Although it is known that the QT interval is dependent on the preceding RR interval, QT interval does not vary during respiratory sinus arrhythmia, despite a wide variation in heart rate. To assess the rate of change of the QT interval following an abrupt increase or decrease in heart rate, QT intervals were measured from ECG of healthy, anesthetized, thoracotomized dogs in which a junctional rhythm had been induced by destroying the sinoatrial node. Atria were paced at 800- or 600-millisecond cycle durations until a steady state was reached, and then the cycle duration was changed suddenly to a new cycle duration (600 or 800 milliseconds, respectively). The time and number of heart beats required until the QT interval achieved a value of 63% (1 time constant) of the new steady state were calculated. Time constants for change in QT interval vs the number of beats following the change were 2.8 (SD = 1.3 s) seconds when heart rate was accelerated and 4.7 (SD = 2.1 s) seconds when heart rate was slowed. Differences were not statistically significant. The time constants for change in QT interval duration vs duration after the sudden change in heart rate were 1.7 (SD = 0.8 s) seconds when heart rate was accelerated and 3.7 (SD = 1.7 s) seconds when heart rate was slowed. These time constants differed significantly (P < 0.01). Response of QT interval, therefore, depended on the number of heart beats following sudden change in heart rate, but not time, except as time determined the number of heart beats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7879989 TI - Psychosocial and behavioral predictors of longevity. The aging and death of the "termites". AB - Impulsive, undercontrolled personalities and major family stresses are known predictors of impaired adjustment, but long-term health effects are unclear. In an archival prospective cohort design, we followed up on L. M. Terman's (Terman & Oden, 1947) sample of gifted children by collecting and coding death certificates for the half of the sample that is now dead. Statistical survival analyses were used to predict longevity and cause of death as a function of parental divorce during childhood, unstable marriage patterns in adulthood, childhood personality, adult adjustment, and possible mediating health behaviors. Psychosocial factors emerged as important risks for premature mortality. PMID- 7879990 TI - Motor development. A new synthesis. AB - The study of the acquisition of motor skills, long moribund in developmental psychology, has seen a renaissance in the last decade. Inspired by contemporary work in movement science, perceptual psychology, neuroscience, and dynamic systems theory, multidisciplinary approaches are affording new insights into the processes by which infants and children learn to control their bodies. In particular, the new synthesis emphasizes the multicausal, fluid, contextual, and self-organizing nature of developmental change, the unity of perception, action, and cognition, and the role of exploration and selection in the emergence of new behavior. Studies are concerned less with how children perform and more with how the components cooperate to produce stability or engender change. Such process approaches make moot the traditional nature-nurture debates. PMID- 7879991 TI - [Congenital hypothyroidism: from screening to diagnostic and therapeutic follow up]. PMID- 7879992 TI - [Models of the organization of neonatal screening]. AB - The authors evaluate the different organizational strategies of a congenital hypothyroidism screening program. Positive and negative aspects of laboratory screening tests (TSH only, T4-supplemental TSH, TSH and T4), organization strategies (centralization or decentralization), recall and first follow-up criteria are examined. The authors consider that the necessity for an early diagnostic confirmation can be associated with a precise etiologic diagnosis and an evaluation of the prenatal severity of congenital hypothyroidism factors. Some European and North-American experiences are compared with the activity of a regional Italian screening center. PMID- 7879993 TI - [Neonatal screening in congenital hypothyroidism in Italy. The National Registry]. AB - Neonatal screening for congenital hypothyroidism (CH) began in Italy in 1977 and then progressively developed covering 97% of live births in 1992. The National Register of infants with congenital hypothyroidism was established in 1987 as a project of the Health Ministry and is coordinated by the Italian Institute of Health. The aim of the Register is to provide disease surveillance, to monitor the efficiency and effectiveness of neonatal screening and to allow the identification of possible etiological risk factors in congenital hypothyroidism. The results of the Register provided valuable epidemiological informations about congenital hypothyroidism in Italy and evidenced several areas in whom an increased incidence probably caused by iodine deficiency was observed. Discussion of Register data during annual national meetings has allowed an improvement of the screening program with particular regard to the beginning of therapy with L thyroxine and its dose. Because of the wide spectrum of collected information, the National Register represents a useful tool for developing of collaborative studies concerning some aspects of CH not yet completely elucidated. PMID- 7879994 TI - [The association between hypothyroidism and other congenital defects. The experience of the National Registry in 1987-1992]. AB - This study considers the birth defects (BD) observed from 1987 to 1992 in 35/811 newborns with congenital hypothyroidism (CH) diagnosed by neonatal screening and included in the National Register. The BD incidence was higher than in the general population (4.3 vs 2.5-3%) and especially the one of the congenital heart diseases, (CHD) (2.1 vs 0.3-0.8%). Furthermore the CHD were more frequently observed in females than in males (M/F = 1/4.7). These results seem not to be casual but the reasons remain unknown. The most frequent CHD observed were the septal defects and the pulmonary stenosis. Further are presented and discussed the main findings of 2 groups of CH patients (with and without BD). These results are a good instance of the National Register applications, also for less known aspects of the CH like the concomitant BD. PMID- 7879995 TI - [The evaluation of the risk factors for congenital hypothyroidism: the outlook of a case-control study]. AB - The availability of a National Register of congenital hypothyroid infants allowed to perform descriptive studies on characteristics of the cases and the efficiency of the neonatal screening. Continuous and exhaustive recording of data concerning congenital hypothyroidism cases provided valuable epidemiological informations about congenital hypothyroidism in Italy. Moreover, the National Register allowed to develop a network of collaboration which can promote a population based case control study. As the etiopathogenesis of congenital hypothyroidism has not been completely elucidated, performing of a case-control study can contribute to evidence the most important risk factors of congenital hypothyroidism and to improve the prevention also by prenatal diagnosis of this disease. Screening centers will be involved in the study and questionnaires of the National Register for congenital hypothyroidism will be used to record case and control informations. A biological bank concerning cases, controls and their parents, will be organized. PMID- 7879996 TI - Congenital hypothyroidism: etiology and pathogenesis. AB - Congenital hypothyroidism is a frequently occurring condition with possibly severe and irreversible consequences. Most of the cases are due to thyroid ectopia, aplasia or hypoplasia and are sporadic in occurrence. Inherited defects of thyroid hormone biosynthesis, secretion and utilization represent a minor, although not insignificant, fraction of the cases of congenital hypothyroidism. In a number of cases, transient congenital hypothyroidism can be due to such causes as maternal exposure to antithyroid drugs or excess iodine, transplacental transfer of blocking antibodies or endemic iodine deficiency. The latter is still a matter of concern in selected geographical areas. Both sporadic and familial cases of hypothalamic-pituitary hypothyroidism are quite rare. Early diagnosis of congenital hypothyroidism by mass screening programs is of the foremost importance for the prevention of long-term sequelae. The molecular defect has been elucidated in a number of inherited defects of thyroid hormone biosynthesis, secretion and utilization. These include impaired thyroidal response to thyroid stimulating hormone (TSH) due to an altered TSH receptor, defective synthesis of thyroglobulin, defective synthesis of thyroid peroxidase, generalized resistance to thyroid hormone, and familial isolated TSH deficiency. It is anticipated that, as more mutations become available for detailed molecular analysis, further advances in our knowledge of the molecular aspects of thyroid function will ensue in the near future. PMID- 7879997 TI - [Transient neonatal hypothyroidism and iodine deficiency]. AB - Iodine is the essential constituent of thyroid hormones. Iodine deficiency disorders, ranging from endemic goiter to cretinism, result from low dietary intake of iodine. The fetus and the newborn are more sensitive than adults to a reduced environmental iodine supply, and in iodine-deficient areas, transient neonatal hypothyroidism is frequently observed. This transient thyroid failure may be associated with neonatal goiter. Border-line elevated neonatal TSH levels frequently occur in iodine deficient areas, and result in a higher recalling rate in the screening for congenital hypothyroidism. Iodine prophylaxis is highly effective in preventing the development of iodine deficiency disorders including transient neonatal hypothyroidism. Since iodine prophylaxis in Italy is inadequate, variable degrees of iodine deficiency are still present all-over the Country, and are responsible of a higher incidence of transient neonatal hypothyroidism or hyperthyrotropinemia. Educational programs for the general population, health professionals, and decision makers are essential for a successful iodine prophylaxis. Elimination of iodine deficiency by the year 2000 has been recently pledged by WHO/UNICEF. This goal is feasible if pursued with sufficient vigor and resources. PMID- 7879998 TI - [Thyroid autoimmunity and congenital hypothyroidism]. AB - The involvement of thyroid autoimmunity in the pathogenesis of sporadic congenital hypothyroidism is still incompletely understood. While antithyroglobulin and anti-thyroperoxidase antibodies are harmless, the transplacental passage of TSH receptor antibodies with blocking activity from a mother with autoimmune thyroiditis to the fetus is responsible of transient neonatal hypothyroidism in the baby. This is however a rare condition. Thyroid growth blocking antibodies have been described in healthy mothers of children with permanent congenital hypothyroidism due to thyroid dysgenesis, but this observation was not confirmed in other studies including our own. Antibodies producing cell mediated cytotoxicity (ADCC), either transferred from the mother or due to an autoimmune thyroiditis developing in utero, might be involved in the pathogenesis of permanent congenital hypothyroidism. However, this hypothesis requires confirmation in more extensive studies. PMID- 7879999 TI - [The therapy of congenital hypothyroidism]. AB - In congenital hypothyroidism precocious diagnosis and consequent replacement therapy are necessary to prevent neurological irreversible damage caused by postnatal thyroid hormone deficiency. Synthetic L-thyroxine is the useful drug, that has to be administered in fasting condition to have the best absorption. Some points about the treatment are still discussed, such initial L-thyroxine dosage, biochemical control parameters and psycho-intellectual outcome in treated patients. The mean initial dosage in Italy increased from 7.5 +/- 2.2 micrograms/kg/day in 1987-90 period to 8.5 +/- 2.5 micrograms/kg/day in 1991, at a mean starting age of 34 and 26 days respectively. Therefore the dosage is modulated on the basis of serum levels of thyroid hormones and clinical signs. Some patients, in spite of a correct dosage of L-thyroxine, show a deficient suppression of TSH circulating level. In our experience this finding is sometimes due to the non-observance of the fasting condition when the drug is administered. Patients precociously identified by neonatal screening and correctly treated have a good mental and statural prognosis. In these patients, the psycho-intellectual development is better than in those diagnosed later clinically. PMID- 7880000 TI - [Transient changes in thyroid function in the neonatal period]. AB - Transient neonatal hypothyroidism (TH) is a state biochemically characterized by altered TSH and T4 values at screening and subsequently confirmed by serum analysis. TH can go or not go along with clinical manifestations of hypothyroidism and evolves to the normalization of the thyroid functional capacity independently of substitutive therapy. In addition to the complete TH the application of screening programs for congenital hypothyroidism has enable to acknowledge partial changes of the thyroid functional capacity in the neonatal age characterized by isolated anomalies of the individual hormonal parameters. Since the incidence of neonatal TH in Italy is remarkably high (the forms of complete TH being not less than 20% of the hypothyroidism cases diagnosed at the screening) we want to provide an overview of the latest acquisitions regarding TH. Finally the indications for treatment of the various forms of TH, a still controversial matter, are considered, in consideration of the primary role played by thyroid hormones on the development of central nervous system in the perinatal age. PMID- 7880001 TI - [The instrumental and clinical laboratory follow-up of congenital hypothyroidism]. AB - Early diagnosis, L-tiroxine therapy and adequate follow-up are determinant to remove the damages resulting from hormone deficiency in congenital hypothyroidism (CH). In order to achieve a better intellectual development, the authors suggest some guidelines for a correct follow-up on the basis of their personal experience on a population of 160 children with CH. These guidelines include monitored therapy, biochemical controls, instrumental investigations, clinical and auxological serial examinations. To better predict the mental outcome of these patients as adults, the authors propose a longer follow-up till adolescents, especially in the children with more severe hypothyroidism at diagnosis. PMID- 7880002 TI - [Neuropsychological follow-up in congenital hypothyroidism]. AB - Thyroid hormones play a key role in a number of critical neuromaturational processes, including neurogenesis, neuronal migration, synaptogenesis and myelination. Even in case of early treated CH children we cannot exclude the consequences of thyroid hormones deficiency in the critical pre and post-natal period. So, it is still useful to follow-up the neuropsychological development of CH children. IRCCS "Stella Maris" has been involved in research in this subject for several years with the collaboration the Institute of Endocrinology and of the Institute of Pediatrics (University of Pisa). According to our experience and to the results literature we propose to continue the follow-up studies with a simple, unique methodology that could be diffused to every screening center in Italy. PMID- 7880003 TI - [Contribution and limitations of substitution treatment in health care for drug abusers. Conference proceedings. 23-25 June 1994]. PMID- 7880004 TI - [How do the substitution programs help in social integration of drug addicts?]. PMID- 7880005 TI - [Comparative pharmacodynamics of methadone, buprenorphine and codeine]. PMID- 7880006 TI - [Benzodiazepines and methadone: a dangerous combination?]. PMID- 7880007 TI - [Comparative value of buprenorphine and methadone]. PMID- 7880008 TI - [Reliability and role of urinary assays within the framework of "methadone programs"]. PMID- 7880009 TI - [Buprenorphine in the treatment of opiate dependence]. PMID- 7880010 TI - [Role of LAAM, methadone and naltrexone in the care of opiate dependence. Experience in Portugal]. PMID- 7880011 TI - [Substitution treatments in Geneva]. PMID- 7880012 TI - Methadone treatment programmes in the United Kingdom. PMID- 7880013 TI - [Report on the methadone program at the Centre Pierre-Nicole]. PMID- 7880014 TI - [Report on prescriptions of methadone at the Espace Murger, Hopital F.-Widal (1984-1993)]. PMID- 7880015 TI - [Treatment of heroin addiction by methadone. Specialized care]. PMID- 7880016 TI - [Administrative, social and clinical facilities of the implementation of the methadone program in Bordeaux]. PMID- 7880017 TI - [Report on the buprenorphine substitution experience in urban medicine in Belgium]. PMID- 7880018 TI - [Report on substitution with medical assistance by general practitioners in France]. PMID- 7880019 TI - [Value and limitations of substitution treatments in the care of drug addicts]. PMID- 7880020 TI - [Indications for benzodiazepines in the care of drug addicts]. PMID- 7880021 TI - [How to treat a patient with AIDS and drug dependence unwilling and/or unable to withdraw? Give substitution drugs at the hospital? Should substitution be continued after discharge? Is substitution a useful adjuvant to programs designed to prevent opportunistic diseases?] opportunisticinfections?]. PMID- 7880022 TI - [What are the objective and cultural conditions of inclusion in substitution treatments of patients belonging to the Antillean minority]. PMID- 7880023 TI - [What are objective and cultural conditions of the inclusion in substitution treatments of patients belonging to the Algerian minority]. PMID- 7880024 TI - [Comparison of substitution practices by French and foreign physicians]. PMID- 7880025 TI - [Can the general practitioner care for outpatient drug addicts without substitution treatments? What products can he use?]. PMID- 7880026 TI - [Proposal of dispensary pharmacists to improve current practices of substitution. Self-substitution and prescribed substitution]. PMID- 7880027 TI - [Role of pharmacy professionals in the network of drug addict care. Follow-up: buprenorphine, methadone, general practitioner network]. PMID- 7880029 TI - [Epidemiology of drug dependence and real-life experiences]. PMID- 7880028 TI - [Criteria of evaluation of results of drug dependence substitution programs as a function of objectives and means: high threshold, low threshold, withdrawal...]. PMID- 7880031 TI - [Substitution practices in Europe and reduction of risks]. PMID- 7880030 TI - [Complementary prevention actions as a means of reducing risks]. PMID- 7880032 TI - [Do substitution treatments reduce the incidence of human immunodeficiency virus infections in intravenous heroin addicts? Review of pertinent literature]. PMID- 7880034 TI - [Incidence of the development of substitution treatments and specialized care centers]. PMID- 7880033 TI - [How would the development of substitution treatments modify the care of drug addicts?]. PMID- 7880035 TI - [Will knowledge of substitute treatments modify the frame of therapeutic counseling and favor alternatives to imprisonment?]. PMID- 7880036 TI - [Are substitution practices indicated in withdrawal within the framework of health care of drug addicts and according to what modalities?]. PMID- 7880037 TI - [Reflections apropos of methadone: posology and use in the United States]. PMID- 7880039 TI - [How can the penitentiary physician use substitution treatments?]. PMID- 7880038 TI - Biological correlates of methadone maintenance pharmacotherapy. PMID- 7880040 TI - [Are maintenance substitution practices indicated in the framework of health care of drug addicts?]. PMID- 7880041 TI - [When and how one can leave a methadone treatment program?]. PMID- 7880042 TI - [Can substitution practices be indicated in withdrawal programs for heroin addicts?]. PMID- 7880045 TI - Complication outcomes based on preoperative admission and length of stay for primary palatoplasty and cleft lip/palate revision in children aged 1 to 6 years. AB - With increasing focus on outcome studies, there is continued need for data about whether same-day admission and reduced hospital stay have adverse effects on surgical treatment, including that for cleft lip and palate. In this study, medical records were inspected for all cleft lip and palate patients, aged 1 to 6 years, who had primary palatoplasty or cleft lip/palate revision in this treatment center between 1978 and 1992 (N = 329). Length of stay for 251 (96.5%) of the 260 subjects admitted the day before surgery was from 4 to 7 days; 9 remained in the hospital longer than 8 days. Length of stay for 67 (97.1%) of 69 patients admitted the day of surgery was from 2 to 3 days; 2 were in the hospital for 7 days, and none for 8 or more days. Thirty-seven instances of surgical complications were reported for the 260 patients admitted the day before surgery (14.2%). Twelve complications (17.4%) were recorded for the 69 patients admitted the day of surgery. There was no significant difference in the number of complications between the two groups of patients (Fisher's exact test, p = 0.5682). There was no significant difference in the types of complications observed between the two groups (Fisher's exact test). Surgery was performed at age 1 year for 61 of the 69 patients admitted on the day of surgery (88.4%). The mean age of this group was significantly younger than that of patients operated on earlier than 1989 and admitted on the day before surgery (Wilcoxon's test, p = .0001, Z = 4.48).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880043 TI - Substitution programmes. Advantages and disadvantages. Maintenance or adjuvant therapy. Access to health care and social reintegration. PMID- 7880044 TI - Risk of dissemination of cancer to flap donor sites during immediate reconstructive surgery. AB - We reviewed a series of 617 immediate reconstructions with distant flaps of defects caused by extirpation of malignant tumors to determine the incidence of tumor implantation in the flap donor sites. In this large series, there was only one instance of tumor dissemination to a flap donor site. We conclude that, despite possible theoretical concerns about host immunosuppression caused by surgical stress, the risk of tumor dissemination to flap donor sites as a consequence of immediate reconstruction is negligible. PMID- 7880046 TI - Free vascularized iliac osteomusculocutaneous flaps based on the lateral circumflex femoral system for repair of large mandibular defects. AB - A free vascularized iliac osteocutaneous flap based on the ascending and transverse branches of the lateral circumflex femoral system was studied by cadaveric investigation. These composite flaps were successfully used in 2 patients with both large mandibular and soft-tissue defects. The advantages of this flap are that (1) the distal portion of the flap is relatively thin, (2) the pedicle vessels are long and large, (3) the skin territory is extremely wide, (4) repositioning of the patient during the operation is unnecessary, (5) the flap can be elevated while the recipient mandibular region is resected by two teams because the donor site is far from the head and neck regions, (6) the donor scar is in an unexposed area and its location permits easy concealment, and (7) subtotal loss of the mandible can be reconstructed with the use of split crests from either side of the ilium because the external and the internal cortices are fed independently by the lateral circumflex femoral and the deep circumflex iliac systems. This appears to be a new concept for reconstruction of total mandibular loss. PMID- 7880047 TI - "Mask lifting" in orthomorphic facial correction of bilateral cleft palate. AB - In bilateral cleft palate patients, abnormal obliquity and narrowness of orbits are noted on radiographs, computed tomographic scans, and magnetic resonance imaging investigations. Deformity of bony structures (increase in transverse length) is sometimes associated with malposition of eyelids, which results in a typical antimongoloid facies. Five patients were treated, and we report our series to illustrate the problem and its correction using the "mask-lift" procedure, initially described by Tessier and Krastinova. PMID- 7880048 TI - A rat model for capsular contracture: the effects of surface texturing. AB - There has been ongoing clinical and laboratory research to determine the role of surface morphology on capsular contracture. The purpose of this study was to develop a rat model in which capsular contracture occurred frequently and to determine whether surface texturing had any effect on the incidence or degree of capsular contracture as determined by in vivo biomechanical analysis of tissue modulus and histological examination of the tissue at the capsule-implant interface. A new sublatissimus implantation site in the rat was developed in an attempt to avoid subpannicular placement, which has been associated with inconsistent results because of contracture despite texturing, and a high rate of implant exposure secondary to trauma. Each rat (N = 43) was implanted with two devices--one smooth-surface 6-ml implant and one textured Biocell 6-ml implant- both with remote ports to allow for biomechanical analysis. Evaluation was carried out at 1, 2, and 3 months (n = 10) and 6 months (n = 5). Biomechanical evaluation of the implants was carried out in vivo and anonymously. The animals were then killed, and sectioning of the overlying capsule-implant interface from the dome of the implant was performed. Histological evaluation was carried out anonymously with regards to the implant type. Capsular contracture developed in smooth-surface devices in 95% of sites; this became evident on biomechanical analysis at 2 months and progressed to 3 months, after which it remained relatively stable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880049 TI - Mechanical anastomosis of nerves: a histological and functional comparison to conventional suturing. AB - The use of a mechanical coupling device in microsurgery offers speed of application in addition to a secure vascular union. Despite its success in a vascular setting, mechanical coupling device nerve repair remains to be studied. Forty-five male rats were tested over 7- and 14-week study periods. One half of the animals underwent primary suture repairs for transected sciatic nerves, and the remainder of the animals had their nerves repaired using a mechanical coupling device. Postoperative analysis consisted of histological evaluation of pre- and postrepair site nerve morphology (axonal continuity and counts) as well as functional testing using walking track analysis. Mechanical coupling device coaptation of the nerves using the epineurium was done in approximately one half the time compared with conventional suturing. After both 7 and 14 weeks postoperatively, walking track analysis showed no difference in the amount of functional return between the two repair groups. No animal exhibited complete return of function. Axonal continuity occurred across both repairs without significant difference in their pre- and postrepair axonal counts. Although no clear advantage was seen in this study, the concept of mechanical nerve coupling merits further investigation based on its potential clinical utility. PMID- 7880050 TI - Formation of independently revascularized small-bowel segments using pedicled omental flaps. AB - This represents the initial report of intestinal revascularization with pedicled omental flaps producing bowel segments that are capable of surviving without their native mesenteric perfusion. In 10 mongrel dogs, a pedicled omental flap supplied by the left gastroepiploic arcade was sutured along a seromuscular incision in the antimesenteric border of an isolated 15-cm segment of proximal jejunum. After 5 weeks, to allow for revascularization, the mesenteric blood supply to each isolated segment was completely divided at its base. Total survival of all bowel segments occurred based solely on omental perfusion. With each animal serving as its own control, the capacity for absorption of D-xylose in isolated jejunal segments perfused only by an omental "neomesentery" was demonstrated to be equal to control jejunal segments perfused by their native mesenteries. Arteriographic evaluation of the revascularization process revealed that the omental "neomesentery" is capable of supplying the entire isolated bowel segment through anastomoses with the vascular channels already present in the bowel wall. The mechanism of the revascularization process was further explored and found to be intimately dependent on an intact marginal arterial arcade in the mesentery. PMID- 7880051 TI - Enhancement of intestinal absorptive capacity with omental flaps. AB - The ability of pedicled omental flaps to revascularize isolated jejunal segments was determined in the initial phase of this project. These bowel segments were capable of surviving independent of their mesenteric perfusion, and absorptive function was equal to that of controls as measured by D-xylose assays. In the second phase of this research, we studied in 10 dogs the absorptive capacity of isolated jejunal segments with both an intact mesentery and an omental flap sutured to the antimesenteric border compared with controls that were perfused only by the mesentery. Absorption was measured at 1, 2, 5, and 10 weeks after application of the omental flap. Absorptive function was augmented an average of 25.8% at 2 weeks, reaching 67.6% (p < 0.001) at 5 weeks. This result remained consistent at 10 weeks. Laser Doppler and colored microsphere studies were performed during a secondary laparotomy at 10 weeks and revealed 42.3% and 53.5% increases, respectively, in blood flow to bowel segments receiving both mesenteric and omental perfusion. This finding suggested that the augmentation of absorptive function was a result of increased blood flow. PMID- 7880052 TI - Ethanol injection sclerotherapy for Baker's cyst, thyroglossal duct cyst, and branchial cleft cyst. AB - Six patients with Baker's cysts, 3 with branchial cleft cysts, and 2 with thyroglossal duct cysts were treated with percutaneous aspiration and absolute ethanol sclerotherapy using a 7-French pigtail catheter. Cystography was performed before ethanol injection to confirm that there was no extravasation and that it was a monocystic lesion. One recurrence of a Baker's cyst was revealed in follow-up examinations, which ranged from 11 months to 36 months (mean, 25 months). The major complication of hypoesthesia of the popliteal region was observed in 1 patient treated for Baker's cyst. The results of this series suggest that ethanol sclerotherapy is the treatment of choice for Baker's cyst, branchial cleft cyst, and thyroglossal duct cyst. PMID- 7880053 TI - Vitamin C reduces ischemia-reperfusion injury in a rat epigastric island skin flap model. AB - Free radicals have been implicated in the cause of ischemia-reperfusion injury. Various agents have been used in an attempt to reduce ischemia-reperfusion injury pharmacologically, including free radical scavengers. Vitamin C (ascorbic acid), a well-known free radical scavenger, has not, to the best of our knowledge, been evaluated in this respect. Previous work at our institution has shown that vitamin C decreases capillary permeability, thus significantly reducing fluid resuscitation requirements in postburn cases. Because this is due in part to the scavenging effect of vitamin C on free radicals, we investigated the role, if any, of vitamin C on ischemia-reperfusion injury in a rat epigastric island skin flap model. Twenty-four adult Sprague-Dawley rats were divided into control and vitamin C groups. Superficial epigastric island skin flaps measuring 6.0 x 3.5 cm were raised. Pedicles were isolated and occluded with microvascular clamps for 6 hours. The flaps were then sutured back to their beds over Steri-Drape barriers. Fifteen minutes before reperfusion, the control group flaps were perfused via femoral artery cannulation with normal saline (2.5 ml/kg). The vitamin C-treated group was perfused in a similar fashion with 2.5 ml/kg of a vitamin C/normal saline solution (27 mg/ml). The animals were observed for 7 days, and the percentage of flap survival was determined using a paper template technique. The vitamin C-treated group demonstrated a significantly higher percentage of flap survival than did the control group (25.8% mean vs. 7.5% mean, p < 0.025). In this animal model, vitamin C reduced or limited reperfusion injury after 6 hours of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880054 TI - Silicone implant rupture diagnosis using computed tomography: a case report and experience with 22 surgically removed implants. AB - Silicone elastomer shell rupture is a complication of silicone implants. To date, the rate of implant rupture has not been well documented. Magnetic resonance imaging and sonography are noninvasive breast implant imaging modalities that have been shown to be useful in evaluating the integrity of implants. We present a case of rupture detection using a follow-up computed tomographic (CT) scan of a breast cancer patient, which prompted us to use CT scans to evaluate explants of patients undergoing implant removal surgery. The purpose of the investigation was to evaluate the effectiveness of CT scan in detecting rupture. CT scan was performed on 22 explants with intact capsules, for which 17 ruptures were confirmed: 16 true-positive ruptures, 5 true-negative ruptures, O false-positive ruptures, and 1 false-negative rupture were identified. CT scan was shown to be highly sensitive and specific in rupture detection, comparable to magnetic resonance imaging. Although CT scans are consistently reliable, patients are exposed to ionizing radiation; therefore, it is not recommended for patients with augmentation mammoplasty. This study characterizes the appearance of implant rupture on CT scan, which may be useful in evaluating breast cancer patients reconstructed with silicone implants. PMID- 7880055 TI - Nasal reconstruction using free temporoparietal fascial flap transfer (Upton's method). AB - Reconstructive surgery for severe nasal deformity after radical operation of the maxillary antrum was performed by free temporoparietal fascia transfer to the nasal membrane, followed by secondary-rib cartilage grafting. Correction of nasal deformity caused by severe scar contracture and tissue defect in the nasal cavity has been considered difficult. However, skin grafting with temporoparietal fascia transfer to the nasal membrane can make it possible to perform cartilage grafting without exposure. This method should be nominated as a useful procedure for correction of severe nasal deformity caused by nasal membranous scar contracture. PMID- 7880056 TI - Arteriovenous fistula of the scalp after hair transplantation treated by endovascular embolization. AB - A 27-year-old patient acquired an arteriovenous fistula after punch graft hair transplantation. This lesion was treated by (percutaneous) puncture and injection of a liquid acrylic (N-butyl-2-cyanoacrylate). The fistula was completely obliterated by the endovascular therapy without the need for additional vascular or cosmetic surgery. Endovascular therapy may be helpful as an adjunctive or primary treatment modality for iatrogenic or post-trauma fistulas. PMID- 7880057 TI - Fracture of the radial forearm osteocutaneous donor site. AB - Since the introduction of the osteocutaneous radial forearm flap in 1983, fractures of the radius have been reported to occur in approximately 30% of cases. Fracture of the donor forearm has been the cause of the most significant morbidity, and the difficulty in management of these fractures has been reported. We report our experience in managing three fractures involving the donor forearm. Optimum results can be achieved by early stabilization with external fixation and vascularized bone grafting. Excessive resection of the radius should be avoided and alternative sources of vascularized bone used to avoid mutilation of the forearm. PMID- 7880059 TI - Scar-length reduction by ring-shaped expansion. AB - Conventional tissue expansion with rectangular or round expanders often results in considerable dog-ear formation and, after resection, in lengthening of the final scar. The resulting scar is, always much longer than the maximal diameter of the skin lesion. These disadvantages are partially avoided by the use of croissant-shaped expanders. Taking the idea of the croissant-shaped expander and thinking further in terms of differential expansion, a new expander has been designed. It consists of a ring-shaped expander that is placed under the normal skin around the lesion. When the appropriate expansion is reached, the skin lesion is excised and the defect is closed with a running subcuticular suture, pulling as much skin as possible centripetally. The resulting scar is shorter than the maximal diameter of the skin lesion. The new expander has been tested in two patients in regions that are reputed for poor scar quality (the back and the upper arm). The results are encouraging. PMID- 7880058 TI - Treatment of vitiligo with melanocytic grafting. AB - This case report documents the treatment of extensive vitiligo with melanocytic grafting using ultra-thin, split-thickness skin grafts. Results, limitations, and disadvantages are discussed. PMID- 7880060 TI - Fibromuscular dysplasia of distal radial and ulnar arteries: uncommon cause of digital ischemia. AB - Fibromuscular dysplasia is an uncommon angiopathy that is principally observed in the renal and carotid arteries. Digital ischemia resulting from fibromuscular dysplasia of the forearm arteries is a rare occurrence. This article describes a case of distal radial and ulnar artery fibromuscular dysplasia presenting as paresthesia, claudication, and finger ulceration. Angiography was diagnostic in visualizing the characteristic "string of beads" appearance. In addition to the typical histological findings, we also observed a previously undescribed pathological finding. Surgical management involved resection of the diseased segment and primary anastomosis. PMID- 7880061 TI - Aggressive pilomatricoma in childhood. AB - Pilomatricoma (calcifying epithelioma) is a benign tumor of the hair matrix cells that presents most frequently in childhood. Most are benign and slow growing and do not recur after excision. A small number of aggressive or malignant variants have been reported that recur if not widely excised. We report on an aggressive variant occurring in a 4-year-old boy and advise caution in treating cutaneous "cysts." PMID- 7880062 TI - Multiple recurrent benign schwannomas of deep and superficial nerves of the upper extremity: a new variant of segmental neurofibromatosis. AB - Benign schwannomas of the brachial plexus are uncommon tumors, first described in the late 19th century. These lesions, which are histologically benign, can generally be excised without sacrifice of neural elements. We present the first known case of multiple concurrent and recurrent benign schwannomas of the upper extremity in an individual who demonstrated no other evidence of neurofibromatosis, and we suggest that this case may represent a new subtype of type V neurofibromatosis. PMID- 7880063 TI - Adiposis dolorosa (Dercum's disease): 10-year follow-up. AB - Adiposis dolorosa is a disease characterized by painful, subcutaneous fatty tumors. This disorder usually occurs in obese, postmenopausal women and is associated with weakness and mental disturbances such as depression, confusion, lethargy, and dementia. The cause is unknown, and there is no specific treatment. Pain may be relieved by steroids, intravenous lidocaine, or analgesics. Surgical treatment consists of excision or liposuction of the painful masses. We present two cases of adiposis dolorosa in men, with a follow-up of more than 10 years. PMID- 7880064 TI - Extramammary Paget's disease of the scrotum. AB - This case report describes a patient with extramamary Paget's disease of the scrotum. Treatment consisted of excision and primary closure with local advancement flaps. A review of the literature and treatment of extramammary Paget's disease are discussed. PMID- 7880065 TI - The gonial angle stripper: an instrument for the treatment of prominent gonial angle. AB - In the Orient, a prominent gonial angle, so-called benign masseteric hypertrophy, is rather common and considered unattractive. Therefore, its surgical correction is one of the most popular forms of facial skeletal contouring. For accurate and safe osteotomy of the mandibular angle region, a gonial angle stripper was specially invented. It has a small projection that will ease identification of the osteotomy line in a narrow operative field. The tool has been clinically used in eight patients to prove its usefulness, especially for a posteriorly developed mandibular angle. PMID- 7880066 TI - The cleft earlobe: a review of methods of treatment. AB - The plastic surgeon must frequently deal with the aesthetic repair of cleft earlobe deformities. Many techniques have been described, each claiming to achieve the best results. In this review of the literature, we discuss the various operations for the treatment of this condition. A classification of the traumatic earlobe clefts is proposed, and some basic principles for surgical treatment are suggested. PMID- 7880067 TI - A promise kept. PMID- 7880068 TI - False-positive rupture on magnetic resonance imaging. PMID- 7880069 TI - Re: Multiagent pharmacotherapy to enhance skin flap survival: lack of additive effect of nitroglycerin and allopurinol. PMID- 7880070 TI - The clinical biochemistry of the menopause and hormone replacement therapy. PMID- 7880071 TI - Determination of ammonia in biological fluids. PMID- 7880072 TI - Determination of glycated apolipoprotein B in serum by a combination of affinity chromatography and immunonephelometry. AB - We have developed and optimized a procedure for the quantitation of non enzymatically glycated apolipoprotein B (apo B). Glycated and non-glycated apo B were separated from serum using m-aminophenylboronate affinity chromatography, determined by immunophelometry and the percentage of glycated apo B was calculated. The measuring range of the assay was 2.9-185 mg/dL apo B. The within- and between-run coefficients of variation were < 7.4% and 14.6%, respectively, and recovery was > 98%. Free glucose in serum did not affect the results at concentrations below 25 mmol/L. In 45 non-diabetic subjects the mean concentration of glycated apo B was 4.3% (SD 1%). In type 1 (n = 17) and Type 2 (n = 60) diabetic patients the mean glycated apo B concentrations were 5.3% (SD 0.7%) and 5.9% (SD 1.1%), respectively, significantly higher than in controls (P < 0.001). PMID- 7880074 TI - Reflotron cholesterol measurement in general practice: accuracy and detection of errors. AB - Comparison of cholesterol determinations by nurses using a Reflotron analyser in a general practice setting showed a good correlation with plasma cholesterol determinations by wet chemistry in a clinical biochemistry laboratory. A limited number of comparisons did, however, give a much lower result on the Reflotron. In an experimental situation, small sample volumes (which could result from poor technique) were shown to produce falsely low readings. A simple method which may immediately detect falsely low Reflotron readings is discussed. PMID- 7880073 TI - Expression of gonadotropin-releasing hormone receptor in human epithelial ovarian carcinoma. AB - We have previously demonstrated the presence of gonadotropin-releasing hormone (Gn-RH) messenger ribonucleic acid (mRNA) in epithelial ovarian carcinoma. In this study, the expression of Gn-RH receptor (Gn-RHR) was investigated in human ovarian carcinoma and human ovarian carcinoma cell line. Gn-RHR was determined by [3H]Gn-RH binding assay. Gn-RHR mRNA was determined by reverse transcription polymerase chain reaction using oligonucleotide primers synthesized based on published human Gn-RHR sequence. Specific Gn-RH binding sites were shown to be present in plasma membrane isolated from five ovarian mucinous cystadenocarcinoma samples and one serous cystadenocarcinoma (Kd = 15.3 +/- 8.08 nmol/L). Gn-RHR mRNA was detected in four mucinous cystadenocarcinoma specimens, one serous cystadenocarcinoma, and SK-OV-3 cells, but not in white blood cells. These results suggest that Gn-RH may play an autocrine regulatory role in the growth of ovarian carcinoma. PMID- 7880075 TI - The long-term stability in whole blood of 14 commonly-requested hormone analytes. AB - Concentrations of 14 commonly-requested plasma hormones were measured in octuplicate in each of six subjects to determine their stability when unseparated from red cells for periods up to 1 week. Most of the analytes were stable when stored in this way and although statistically significant changes were recorded, in the great majority of cases the changes seen would have no bearing on the clinical interpretation of the result. In the light of these findings, we would confidently report results of analyses for these hormones in plasma that had remained in contact with red cells at ambient temperature for long periods of time. PMID- 7880076 TI - A visual screening method for lactose maldigestion. PMID- 7880077 TI - Long-term experience of quality assurance of cholesterol testing in a general practice surgery. PMID- 7880078 TI - A glucose quality assessment scheme suitable for use with the visual-read Boehringer Mannheim BM-test 1-44 system. PMID- 7880079 TI - Reliability of glucose measurement using the HemoCue analyser in hypoglycaemia. PMID- 7880080 TI - Cofluorescence enhancement improves immunofluorimetric assay minimum detection limit. PMID- 7880081 TI - Alcoholic ketoacidosis: the late presentation of acidosis in an alcoholic. PMID- 7880082 TI - Erroneous iron level reported in a child with suspected overdose. PMID- 7880083 TI - Modification of Toxi-Lab procedure for enhanced theophylline detection. PMID- 7880084 TI - Calcium metabolism following renal transplantation. PMID- 7880085 TI - Microalbuminuria in type 2 diabetic patients: a cross sectional study. PMID- 7880086 TI - Helicobacter pylori infection in children with recurrent abdominal pain. AB - Forty-eight patients with recurrent abdominal pain were studied endoscopically for the presence of gastritis and Helicobacter pylori infection. Fifteen of these children had histological evidence of gastritis with eight of them having concomitant H. pylori infection. The majority of those with H. pylori infection had severe degrees of acute following chronic gastritis. PMID- 7880087 TI - Urinary tract pathogens and antimicrobial sensitivity patterns in children in Ibadan, Nigeria. AB - A study of bacterial organisms isolated from 65 Nigerian children who had urinary tract infection (UTI) is reported. The predominant isolate in both inpatients and outpatients was Klebsiella species which accounted for 52.8% of cases. Escherichia coli, Pseudomonas spp and Proteus spp accounted for 25.0%, 15.3% and 5.5% of isolates, respectively. All isolates were poorly sensitive to the common first-line drugs used in UTI in our environment, namely, cotrimoxazole and ampicillin, but exhibited good sensitivity to nalidixic acid, nitrofurantoin and ofloxacin. It is recommended that nitrofurantoin and nalidixic acid be used for blind treatment of UTI in Nigerian children in Ibadan while results of culture and sensitivity are awaited. Continuous monitoring of the pattern of organisms isolated in childhood UTI and their antibiotic resistance patterns is recommended as an essential step in guiding blind antibiotic therapy in such cases. PMID- 7880088 TI - Reactogenicity and safety of meningococcal A and C vaccine in Saudi children. AB - During an outbreak caused by group A Neisseria meningitidis in March 1992, groups A and C meningococcal polysaccharide vaccine was administered to 1,168 children aged from 2 to 18 years. Parents were surveyed to ascertain reactions of children to the vaccine and development of invasive group A meningococcal disease after immunization. The most common reactions were mild local pain (21.9%), erythema (12.2%), and swelling at the injection site (7.2%). Only 1.7% of the children experienced fever and 3.7% displayed irritability. The vaccine was well tolerated and all adverse reactions disappeared within 24-48 hours of immunization. No cases of meningitis or sepsis caused by group A meningococci were seen in the 1st 12 months of observation among the vaccinated children. PMID- 7880089 TI - Guillain-Barre syndrome. A prospective clinical study in 25 children and comparison with adults. AB - Children who fulfilled the recognized diagnostic criteria for Guillain-Barre syndrome (GBS) were studied prospectively from 1982. After detailed clinical evaluation and investigation, severity of disease was graded on a disability scale ranging from 1 to 6, and the time taken from the 1st day of illness to reach important clinical landmarks was noted. All children were monitored for a minimum of 1 year and observations on them were then compared with those on 92 adults with GBS seen during the same period. Twenty-five children, evenly distributed between the sexes, were seen between 1982 and 1989 and constituted 22% of all GBS patients seen during this period. Children had a more acute form of onset than adults, 80% becoming bedbound within 7 days, and a higher incidence of cranial nerve palsies (76% vs 55%). The incidence of respiratory paralysis was 40% and of dysautonomia 20%, which was similar to findings in adults. Children fared marginally better than adults: 72% were ambulant at 1 year, 12% bedbound and 16% decreased. The prognosis of ventilated patients was relatively poor in both groups, but children with the hyperacute form of the disease had twice the probability of adults to attain independent walking at 1 year (0.63 vs 0.33). PMID- 7880090 TI - Familial nesidioblastosis: more evidence for autosomal recessive inheritance. AB - Severe neonatal hypoglycaemia in five Saudi Arab infants of both sexes belonging to two families of consanguineous parents is reported. All of these infants needed sub-total pancreatectomy to maintain normoglycaemia. Histopathological studies with immunohistochemistry proved diffuse nesidioblastosis of the pancreas in all five infants. Data obtained from these families and other families reported in the literature strongly suggest that familial nesidioblastosis is an autosomal recessive disorder. Knowledge of the inheritance pattern is important both for genetic counselling and for making a prompt diagnosis in subsequently affected siblings, as delay in appropriate treatment may have serious consequences. PMID- 7880091 TI - Maternal knowledge, attitude and practices regarding childhood acute respiratory infections in Kumasi, Ghana. AB - Acute respiratory infections (ARI) are a major cause of paediatric mortality and morbidity, particularly when associated with delays in treatment. A study of mothers' knowledge, attitudes and practices regarding ARI in their children aged less than 5 years was conducted in an urban Ghanaian population. One hundred and forty-three women traders were interviewed in open air markers in Kumasi, Ghana. Based on Western standards, there was a poor maternal understanding of the aetiology of ARI. A variety of herbal and home care therapies, including some which have potentially harmful effects, were routinely employed for the prophylaxis and treatment of ARI. For example, castor oil and enemas (25.9%) were reported as agents to prevent ARI, and antibiotics were prescribed by the parents in 39.9% for treating coughs. While the mothers exhibited an understanding of symptoms which differentiate between mild and severe ARI, a substantial number indicated that they would delay accessing a health care facility in the presence of the following symptoms which signify severe respiratory distress: dyspnoea (11.2%); tachypnoea (18.9%); chest retraction (21.7%); cough, fever and anorexia (30.0%); and cough, fever and lethargy (57.3%). These findings support the need for an ARI health education programme in Ghana. PMID- 7880092 TI - Seizure recurrence after a first febrile convulsion. AB - In this study, 140 children aged from 6 months to 6 years who presented with a first febrile convulsion at the King Fahad Hofuf Hospital, Al-Hassa, Saudi Arabia were retrospectively identified. Information about these children was obtained from their medical records covering a follow-up period of 3 years from July 1989 to June 1992. Recurrent febrile convulsions occurred in 60 of them (43%). Relevant risk factors that were observed to be significantly associated with seizure recurrence included an age of less than 18 months (odds ratio [OR] = 3.82; 95% confidence interval [CI] = 9.26, 1.58), an initial febrile convulsion that was complex (OR = 4.41; CI = 9.50, 2.05) and a positive family history of febrile convulsions (OR = 4.12; CI = 10.74; 1.58), while a decreased risk of recurrence occurred with a temperature of over 39 degrees C (OR = 4.60; CI = 9.44; 2.24). There was no association between seizure recurrence and the duration of the initial febrile convulsion (OR = 0.93; CI = 2.33; -2.04) or family history of epilepsy (OR = 0.88; CI = 4.22, -3.27). An important observation in the present study is the close association (ORM-H = 2.36; X2M-H = 9.65) between the development of an afebrile convulsion and seizure recurrence among the group of children with CFC. Anticonvulsant prophylaxis should therefore be considered for children whose initial febrile convulsions are complex in nature. PMID- 7880093 TI - Twin children in The Gambia: evidence for genetic regulation of physical characteristics in the presence of sub-optimal nutrition. AB - It has been demonstrated that physical growth characteristics are subject to genetic regulation. However, in developing countries, environmental factors such as food availability and frequent infections are associated with growth faltering which is particularly marked in infancy. We have conducted anthropometric measurements of a cohort of twin children aged less than 14 years living in a rural area of The Gambia to ascertain the extent to which genetic factors influence physical growth in the presence of a sub-optimal diet. Almost 25% of the children were more than 2SD below the median of the reference population in terms of their height-for-age Z score, indicating a marked level of undernutrition. Nevertheless, the within-pair variances were significantly less for monozygous than for dizygous twin pairs for the following variables: height, head circumference and body mass index (p < 0.01); weight (p < 0.02) and mid upper arm circumference (p < 0.1), indicating that there is a strong genetic influence on growth regulation despite the sub-optimal nutrition. PMID- 7880094 TI - Malignant tumours in Omani children. AB - In an effort to understand better the epidemiology of childhood cancer in Oman, a retrospective review of hospital-based biopsy-proven malignant tumours was undertaken. A total of 313 cases of malignant diseases in children between the ages of 0 and 12 years were diagnosed in Oman during the 5-year period from January 1988 to December 1992, inclusive. Leukaemias were the most commonly occurring malignancies (32.3%), followed by lymphomas (29%) and brain tumours (11.2%). The male:female ratio was 1.3:1. The commonest presenting age group was 2 years, the majority of which were leukaemias and lymphomas. Differences and similarities between Omani data and those from other countries are discussed. PMID- 7880095 TI - Furazolidone in multi-resistant childhood typhoid fever. AB - Multi-drug-resistant Salmonella typhi infection is an emerging public health problem in most developing countries. Fifty children up to the age of 12 years whose blood cultures were positive for S. typhi, mostly drug-resistant ones, were treated with oral furazolidone in a prospective year-long study. Defervescence occurred in 96% of the treated group with a mean duration for response of 5.9 days. No clinically significant side-effects were noted. Furazolidone was found to be efficacious, safe and cost-effective in the treatment of most cases of childhood typhoid fever caused by multi-resistant S. typhi. PMID- 7880096 TI - Intracranial haemorrhage and child abuse. AB - Intracranial haemorrhage is a major cause of severe morbidity and mortality in child abuse cases in developed countries. However, similar data are not available in most developing countries. This study therefore aimed to determine the incidence of intracranial haemorrhage amongst all cases of child physical abuse, the nature of the injuries incurred, and the morbidity and mortality resulting therefrom. Among 369 cases of physical abuse seen over a 4-year period, 41 (11.4%) had intracranial haemorrhage, of whom 37 (90%) were 2 years old or less. A history of trauma was present in only eight (20%), of which only two were compatible with the injuries incurred. Subdural haemorrhages accounted for 80% of the cases, with skull fractures present in only nine cases. Fifty-four per cent of the 37 children aged 2 years of age or less had no external signs of trauma, but 11 of them had retinal haemorrhages. This is in contrast to the children older than 2 years of age who all had external signs of trauma. The overall prognosis was dismal with an early mortality of almost 30% (13 cases) and at least seven cases with severe neurological sequelae. These findings are comparable with studies from developed countries which have established that non accidental injury must be considered as a cause of intracranial haemorrhage in any young child, despite the absence of external signs of trauma. PMID- 7880097 TI - Aetiology of stridor in Malaysian children. AB - Eighty-five children who presented with stridor were reviewed in order to determine the aetiology of stridor in these cases. Congenital causes accounted for 57.6% of cases. Laryngomalacia was the commonest congenital abnormality (77.5%). Other common causes of stridor were a foreign body in the airway (acquired) and laryngotracheobronchitis (33.3%) (infective). Tracheostomized children are a problem in developing countries, requiring prolonged hospitalization. We overcome this problem by teaching parents how to maintain the tracheostomy tube at home. PMID- 7880098 TI - Neonatal tuberculosis: a case report. AB - A 3-week-old baby with neonatally acquired tuberculous bronchopneumonia is presented. The diagnosis was considered because the neonate did not respond to conventional management of bronchopneumonia. The importance of including tuberculosis as a differential diagnosis in respiratory disorders, especially in developing countries, is emphasized. PMID- 7880099 TI - Massive hepatomegaly in a 6-week-old infant: is it neuroblastoma? AB - Neuroblastoma is described in a 6-week-old baby presenting with a rapidly enlarging liver. Initial ultrasound examination of the abdomen could not characterize the tumour but a second examination showed a cyst in the superior pole of the kidney which at autopsy was found to be due to adrenal haemorrhage. The role of prenatal and postnatal ultrasonography in the diagnosis of neuroblastoma is emphasized. This tumour is more common in white children in the more industrialized countries, but even in developing countries clinicians should remain alert to its myriad manifestations. PMID- 7880100 TI - [Phase III trial of new anticancer agents from a medical oncologists viewpoint]. AB - The purpose of a phase III study is to establish the efficacy of a new agent (whether it is a single-agent, a combination of drugs or a combined modality approach) compared with the best conventional treatment. Several cytotoxic agents with promising single-agent activity in non-small cell lung cancer have recently been defined. Among them are Navelbine, taxol, taxotere, CPT-11 and gemcitabine. A phase III study of Navelbine has been completed. A study is currently in progress defining activity for taxol in combination with cisplatin. Several aspects in designing a phase III trial of CPT-11 related to the efficiency were discussed, with particular emphasis on the following points considered particularly important, timely, or relevant to this symposium. Firstly, the value of a clinical trial is determined mostly by the importance of the question addressed. After the question of timing has been resolved, the choice of the test and appropriate control treatments is central. The keys to obtaining a reliable answer are the use of randomized treatment allocation, adequate sample size, good data quality, protocol adherence, sufficient follow-up, avoidance of exclusions, appropriate analysis, and lack of data dredging. Participation of a biostatistician is also indispensable for improving the efficiency of comparative clinical trials. PMID- 7880101 TI - [Status quo and problems in phase III trials: view of a trialist]. AB - The quality of clinical trials in Japan has been improving through clear protocol preparation, improvements in methodology, coordinating systems, and so forth. In order to further improvement, the following are discussed: 1) dilemmas regarding adherence of treatment determined by protocol, 2) hospital policy and physician's discretion, 3) systems to support randomized controlled trials in hospital, and 4) systems to help obtain informed consent from subjects. PMID- 7880102 TI - [The present status and problems of phase III clinical trials of the new anti tumor drug-pharmaceutical company's view]. AB - Daiichi Pharmaceutical Co., Ltd. obtained the Japanese manufacturing approval of irinotecan hydrochloride (CPT.-11) in January 1994, which was developed through the collaboration with Yakult Honsha Co., Ltd. Prior to the approval, the manufacturer submitted to the Japanese MHW the draft protocols for phase III studies of the drug required to be conducted after its approval under the Guidelines for the Clinical Evaluation of Anti-tumor Drugs, which was promulgated in February 1991. As these studies were to be conducted as part of post-marketing surveillance, the manufacturer encountered various types of questions and complicated problems in designing the studies. Thus, the present report describes the pharmaceutical company's view on the present status and problems of phase III studies of novel anti-tumor drugs in Japan. PMID- 7880103 TI - [Problems of breast conservation therapy]. AB - Breast conservation therapy (BCT) is now considered an appropriate method to treat stage I-II breast cancer. However, local recurrence after BCT is found in at least 5-10% of the patients. We discussed the problems of BCT, including prognostic factors for local recurrence, optimal surgical technique, management of ductal carcinoma in situ, the clinical usefulness of postsurgical radiotherapy, and the indications for induction chemotherapy for more advanced cases. PMID- 7880104 TI - [Phase III studies of combined chemotherapy and radiation in locally advanced non small-cell lung cancer and limited small-cell lung cancer]. AB - Large phase III studies for lung cancer are reviewed. In an effort to improve survival results in locally advanced inoperable non-small-cell lung cancer (NSCLC), several studies have documented survival advantage for cisplatin + vinka alkaloid followed by radiotherapy (RT) when compared with RT alone. In SCLC, meta analyses show that thoracic radiotherapy moderately improves survival in patients who are treated with combination chemotherapy. The optimum combination of chemotherapy and radiotherapy needs to be established. PMID- 7880105 TI - [Current status of phase III study of combined treatment with radiotherapy and chemotherapy for head and neck cancer]. AB - Concerning the combined treatment with radiotherapy and chemotherapy for head and neck cancer, in general, there are many discrepancies between a single institutional pilot study and a multi-institutional prospective randomized study. Some of the differences depend on the insufficient number of patients entered into the study, since the annual incidence of head and neck cancer is relatively low, and the treatment result varies from site to site as well as the stage of the disease. Several types of bias, including patient selection and positive publications, and factors related to the design and analysis of clinical trials result in additional differences. To solve these problems, we organized the Quality Assurance Research Group in Japan, funded by the Ministry of Health and Welfare for several years. Based on much effort, it was emphasized the need for increased manpower and equipment in radiation oncology, for a quality assurance program of radiotherapy and the preparation of a standard treatment modality using decision tree and surrogate survey. PMID- 7880106 TI - [Cervical cancer--phase III studies of radiation therapy combined modality]. AB - The number of patients with cervical cancer has been constantly reduced but it remains a leading cause of death among gynecologic malignancies in Japan. In 1990, 5,793 patients with cervical cancer were registered and 1,892 cases (32.7%) were stage 0, 2,074 cases (35.8%) were stage I, 991 cases (17.1%) were stage II, 659 cases (11.4%) were stage III and 172 cases (3.0%) were stage IV. Among these patients, about 40% were treated with radiation therapy alone or combined with radiation therapy. The five-year survival rates of stage I, II, III, and IV patients were 83.4%, 65.3%, 40.3% and 13.1%, respectively. Phase III studies have been conducted to compare surgical treatment and radiation therapy, and it is clarified that radiation therapy is equivalent to surgical therapy in young healthy patients with an early-stage tumor, while combined radiation therapy followed by surgery did not improve results over radiation alone. It is thus justified to offer postoperative irradiation to selected patients who have high risk factors in the surgical specimen. Effects of chemotherapy were also compared to radiation therapy. Multiagent chemotherapy such as bleomycin, vincristine, mitomycin C, and cisplatin or bleomycin, ifosphamide and cisplatin are standard regimens for cervical cancer. However, because the toxicity of chemotherapy along with radiation therapy is much higher than that of radiation alone, there is a need to develop an adequate adjuvant chemotherapy regimen for cervical cancer. Other ongoing trials are also discussed. PMID- 7880107 TI - [Development of drugs to overcome drug resistance--basic approaches]. AB - P-glycoprotein plays a key role in the mechanisms of multidrug resistance in experimental tumors as well as in clinical tumors both in acquired and intrinsic type resistance. Thus the therapeutic approaches targeting P-glycoprotein would provide benefits in eradication of drug-resistant tumor cells, although some potential problems concerning side effects still remain to be studied. Practical approaches to overcoming multidrug resistance by targeting the P-glycoprotein would be (1) to use antibodies against P-glycoprotein; and (2) to use agents, including calcium channel blocker-related agents and membrane-modifying agents, that interact with P-glycoprotein. These therapeutic approaches will be discussed in the symposium. PMID- 7880108 TI - [Strategies for the overcoming of drug resistance]. AB - The purpose of the studies for drug resistance could be summarized in the following four points. 1) Mechanisms of acquired drug resistance can be translated to those of inherent resistance. 2) Molecular targets of anticancer drugs can be clarified and accurate application of methods for the overcoming of drug resistance may be possible. 3) Important hints can be obtained for the development of new anticancer agents against molecular targets. 4) Efficient methods can be provided to find new anticancer agents against drug refractory tumors. The clinical strategies for the overcoming of drug resistance are 1) the use of non cross-resistant drugs, 2) the application of the drugs for overcoming resistance, 3) high dose chemotherapy, and 4) the combined use of radiotherapy and surgery. PMID- 7880110 TI - [A pilot study of combination chemotherapy with cyclophosphamide, adriamycin, chronic daily dosing of oral etoposide for patients with SCLC ineligible for intensive chemotherapy]. AB - Twenty-two patients with small cell lung cancer (SCLC) ineligible for intensive chemotherapy were treated with a combination of cyclophosphamide 800 mg/m2 iv day 1, adriamycin iv 40 mg/m2 day 1, and oral etoposide 40 mg/m2 once daily day 1-21. The overall response rate was 72.7% with 2 complete and 14 partial responders. The median survival time was 272 days in LD and 231 days in ED. The side effects were acceptable but not as mild as expected. PMID- 7880109 TI - [Pharmacological study of 5'-DFUR oral administration and the clinical responses against gastrointestinal carcinoma]. AB - In 4 out of 5 patients given 400 mg orally 5'-DFUR before surgery, intratumor 5 FU concentration showed over 150 ng/g. The concentration of either 5-FU or 5' DFUR in the portal and peripheral blood of these patients exceeded the limits of assay. 5-FU concentration in peripheral blood was less than 0.05 micrograms/ml. White blood cell and platelet counts in the patients given 1,600 mg/day (no administration for 2 days/week) of 5'-DFUR for one month were essentially the same with those at the time of start of the treatment. Two of three patients showed minor response following the treatment with 5'-DFUR. Thus, administration of 1,600 mg/day of 5'-DFUR may be considered as an effective treatment of fluopyrimidine against advanced cancer. For the prediction of gastrointestinal side effect, assay of the 5-FU concentration in the portal blood seemed to be useful. PMID- 7880111 TI - [Successful treatment of acute myelomonocytic leukemia developed from MDS with cytarabine ocfosfate (SPAC)]. AB - A 65-year-old female with acute myelomonocytic leukemia (AMMoL) developed from myelodysplastic syndrome (MDS), successfully treated with cytarabine ocfosfate (SPAC) is reported. Ubenimex, calcitriol and corticosteroid had a minor effect on her MDS. Since she had severe anemia and congestive heart failure on developing leukemia, she was treated with oral administration of SPAC, a cytidine deaminase resistant derivative of Ara-C. After the second course of SPAC (200 mg/day, for 14-28 days), marked erythroid bursts were found and she entered complete remission. The samplings of SPAC and its metabolites of SPAC were investigated in 2 cases including this case, but there seemed to be no relation between their content and effects. In AML patients, especially in cases developed from MDS, SPAC might be useful because it can be given orally even in an outpatient. PMID- 7880112 TI - [Cisplatin, 5-fluorouracil and leucovorin combination chemotherapy-added radiation therapy for advanced esophageal cancer--a case report]. AB - Cisplatin, 5-fluorouracil and leucovorin combination chemotherapy added radiation therapy was performed for the treatment of 62-year-old male patient with advanced esophageal cancer who had liver cirrlosis. After the treatment, esophageal lesion disappeared. Only minimal side effect occurred during the treatment. Biochemical modulation chemotherapy combined with radiation therapy is useful for advanced esophageal cancer. PMID- 7880113 TI - [A case of hepatocellular carcinoma with bone metastasis responding to oral administration of UFT]. AB - A 63-year-old male patient with a mass in the left chest wall was referred to our hospital. An osteoclastic area was found in the mass of the left 4th rib by computed tomography; the mass was hard and little movable. There was an irregular and poorly demarcated low-density area, 5 cm in diameter, in the liver anterior superior segment. Aspiration from the mass of the chest wall indicated adenocarcinoma (class V) and forecast of metastatic lesion. The titer of serum AFP showed an extremely high level of 1,100 ng/ml. According to these findings, the patient was diagnosed as having hepatocellular carcinoma with bone metastasis and treated by the administration of oral UFT (300 mg/day). Six months later, the mass in the left chest wall was completely eliminated, the size of the hepatic lesion changed to 2.5 cm, and the titer of AFP decreased to the normal range (8.4 ng/ml). Treatment of hepatocellular carcinoma with bone metastasis is often ineffective, but this is a rare case showing the clinical effectiveness of oral administration of UFT. PMID- 7880114 TI - Osteoporosis in rheumatological practice: questions to be answered. PMID- 7880115 TI - Causes and investigation of increasing dyspnoea in rheumatoid arthritis. AB - Fibrosing alveolitis and bronchiolitis obliterans are two of the many pulmonary manifestations of the connective tissue disorders. When shortness of breath is the main complaint, it is often difficult to diagnose the individual causative lesion from the clinical examination, lung function tests, and chest radiographic findings. In such cases high resolution computed tomography, with its increased sensitivity and specificity for analysis of the pulmonary parenchyma, provides an excellent diagnostic tool for determining the presence and type of pulmonary abnormality. PMID- 7880116 TI - Paraplegia with sclerotic vertebral lesions. PMID- 7880118 TI - Fibromyalgia: why such controversy? PMID- 7880117 TI - Immunolocalisation studies on six matrix metalloproteinases and their inhibitors, TIMP-1 and TIMP-2, in synovia from patients with osteo- and rheumatoid arthritis. AB - OBJECTIVE: To assess the likely importance of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the arthritic process. METHODS: Synovial samples from seven joints with rheumatoid arthritis and three osteoarthritic joints were analysed by indirect immunofluorescence microscopy. Using specific human antisera, we documented the frequencies and distributions of collagenase, stromelysins 1 and 2, matrilysin, gelatinases A and B, TIMP-1, and TIMP-2. RESULTS: Stromelysin 1 was found in all synovia, bound to extracellular matrix, within cells, or both, indicating stromelysin synthesis. Matrilysin was present in only one active inflammatory synovium, and focal synthesis of collagenase and gelatinase A was seen in four synovia. Stromelysin 2 and TIMP-2 were not observed, but TIMP-1 synthesis was seen in five synovia, and in two active synovia the distribution of TIMP-1 positive cells was more widespread than that of MMPs. CONCLUSIONS: The presence of stromelysin 1 in all synovia clearly implicates this enzyme in joint damage. Collagenase, gelatinase A and matrilysin may also have a role in rheumatoid arthritis, but are not significant in osteoarthritis. However, marked regional variations were found in the synthesis of these MMPs, indicating not only that these diseases are episodic but that control of enzyme synthesis is focal. Only TIMP-1 may be considered an inhibitory factor. PMID- 7880119 TI - Interleukin-6 in relation to other proinflammatory cytokines, chemotactic activity and neutrophil activation in rheumatoid synovial fluid. AB - OBJECTIVE: To evaluate the relation between synovial fluid (SF) concentrations of interleukin-6 (IL-6) and other mediators of inflammation which are responsible for joint degradation in rheumatoid arthritis (RA). METHODS: We measured IL-6, IL 1 beta, tumour necrosis factor alpha (TNF alpha), granulocyte macrophage colony stimulating factor, IL-8, and polymorphonuclear leucocyte (PMNL) chemotaxis and degranulation in SF from patients with RA (n = 30) in the early phase of the disease. RESULTS: In a cross-sectional study IL-6 concentrations correlated with those of IL-1 beta, IL-8 and with PMNL activation as reflected by lactoferrin concentrations. In a longitudinal study, changes in IL-6 concentrations correlated with changes in TNF alpha, IL-8 and lactoferrin concentrations. CONCLUSION: IL-6 in SF appears to reflect the local proinflammatory, potentially erosive activity in RA. This supports the use of acute phase proteins, which are mainly induced by IL-6, as variables to monitor the course of RA. PMID- 7880120 TI - Radiolabelled lymphocyte migration in rheumatoid synovitis. AB - OBJECTIVES: To study the ability of technetium-99m hexamethyl propylene amineoxime (HMPAO) labelled lymphocyte scintigraphy to quantify synovial inflammation, and to analyse the kinetics of lymphocyte retention in the joints of patients with rheumatoid arthritis (RA). METHODS: After isolation of the lymphocytes, the cells were radiolabelled in vitro with 250 MBq 99mTc-HMPAO. The scans were performed 30 minutes, three hours and 20 hours after injection. RESULTS: An increase of the scintigram signal obtained at 20 hours was associated with a high joint swelling and joint pain score (F test = 3.07, p < 0.002), but not with the radiological score. A positive joint scintigram was predictive of active synovitis. Although the scintigram variation over time did not reach statistical significance, the kinetics of the scintigram signal tended to differ according to the disease duration: in early RA, active arthritis could be clearly imaged as early as 30 minutes, increased at three hours and the signal intensity persisted at 20 hours. In contrast, in long standing disease, the affected joints were imaged at 30 minutes, persisted unchanged at three hours, and the scintigram score decreased significantly at 20 hours. CONCLUSIONS: The study shows that 99mTc-HMPAO joint scintigraphy may be used to detect and to localise active rheumatoid arthritis. PMID- 7880121 TI - Hip involvement in early rheumatoid arthritis. AB - OBJECTIVE: To study early hip involvement in rheumatoid arthritis (RA) and to evaluate the usefulness of ultrasonography in the detection of hip joint synovitis in RA. METHODS: Study I: The number of hip joint replacements was recorded in a cohort of 113 patients with RA of at least five years disease duration followed from an early stage. Study II: Ultrasonography was evaluated as a method to identify hip joint synovitis in 76 patients with RA of shorter disease duration, by relating it to radiograms and clinical findings. RESULTS: Study I: Twenty one hip joint replacements were performed in 15 of the 113 patients. The median disease duration at the time of first arthroplasty was 48 (range 10-76) months; the annual incidence was approximately constant between two and six years. High disease activity at the start of the study was predictive of requirement for hip prosthesis. Study II: Hip ultrasonography was pathological in 13 of the 76 patients studied, bilaterally in nine. Hip joint synovitis could not be confirmed on clinical grounds only as seven of the patients with positive ultrasonographic findings were asymptomatic, and the remaining six patients had only mild symptoms of hip involvement. Also, six of the 63 patients with normal ultrasonography had mild symptoms. There was no difference regarding demographic, clinical, and laboratory findings in patients with and without hip synovitis. CONCLUSIONS: Early hip joint destruction giving symptoms mostly at a very late stage is frequent in RA. Ultrasonography rather than signs or symptoms could identify patients with hip joint involvement and provide a rationale for early treatment. PMID- 7880122 TI - Rheumatoid arthritis, corticosteroid therapy and hip fracture. AB - OBJECTIVE: To identify the risk of hip fracture in patients with rheumatoid arthritis and those taking corticosteroids. METHODS: In a population based case control study, we compared 300 consecutive patients with hip fracture aged 50 years and over from a defined district and 600 age and sex matched community controls. RESULTS: The risk of hip fracture was increased in patients with rheumatoid arthritis (odds ratio (OR) 2.1; 95% confidence interval (CI) 1.0 to 4.7) and those receiving corticosteroids (OR 2.7; 95% CI 1.2 to 5.8). The risk attributable to rheumatoid arthritis was markedly reduced by adjusting for functional impairment, while that for steroid use remained after adjusting for body mass index, smoking, alcohol, and functional status. CONCLUSIONS: Hip fracture risk is approximately doubled amongst patients with rheumatoid arthritis and among those taking steroids. These risk increases are, to some extent, independent of each other. In rheumatoid arthritis, the risk was most closely associated with functional impairment, whereas steroid use did not appear to be confounded by this variable. PMID- 7880123 TI - Factors affecting radiographic progression of knee osteoarthritis. AB - OBJECTIVES: To evaluate the prognostic significance of patient characteristics and radiographic features at the knee for outcome of knee osteoarthritis. METHODS: This was a prospective observational study of 350 osteoarthritic knees. Clinical and radiographic data were obtained on 188 hospital referred patients (mean age 70, range 34-91 years). RESULTS: Median duration of follow up was two years (range 1-5 years). The majority of patients (48%) reported deterioration, but 23% experienced improvement in symptoms during the study period. Reported exercise tolerance remained unchanged in the majority (62%) and deteriorated in 35%. Change in at least one individual radiographic feature of osteoarthritis was seen in 252 (72%) knees: increase in joint space narrowing occurred in 52%, osteophyte in 32%, cysts in 19%, sclerosis in 14%, and attrition in 30%. Increase in Kellgren grade occurred in 137 (39%) knees. Knee effusion, osteoarthritis at multiple joint sites, and nodal change associated with change in Kellgren grade (odds ratios 1.03, 2.39, and 1.80; 95% confidence intervals (CI) 1.01 to 1.05, 1.16 to 4.93, and 1.02 to 3.17, respectively); warmth at the knee associated with change in any radiographic feature (odds ratio 2.22; 95% CI 1.19 to 4.14). Development of, or increase in, attrition and joint space narrowing associated with worsening symptoms and function and occurred with increased frequency in knees with effusions, clinical warmth and calcium pyrophosphate crystals in synovial fluid (p < 0.05). CONCLUSIONS: A high rate of change, radiographic more than clinical, was seen in osteoarthritic knees during this study. Poor clinical and radiographic outcome associated with calcium pyrophosphate crystal deposition and clinical inflammation as reflected by knee effusion and warmth. PMID- 7880124 TI - PPD and hsp65 induced monoarthritis initiates spontaneous recurrent flares in Lewis rats. AB - OBJECTIVES: To investigate the time course of a monoarthritis induced with the purified protein derivative of tuberculin (PPD) or a recombinant 65 kDa heat shock protein (rhsp65) in two different strains of sensitised rats. METHODS: Wistar and Lewis rats, sensitised with heat killed Mycobacterium tuberculosis in oil, were challenged intraarticularly with PPD or rhsp65 and monitored for six weeks. Inflammation was assessed by joint swelling, histology, and radiographic studies. RESULTS: Sensitised Lewis rats injected with PPD or rhsp65 showed a chronic response with recurrent spontaneous flares, while Wistar rats showed one inflammatory episode. CONCLUSIONS: The Wistar strain response to PPD resembles a transient reactive arthritis, while the response of the Lewis strain mimics the relapsing nature of rheumatoid synovitis, providing an interesting model to determine dominant immunopathogenic mechanisms. PMID- 7880126 TI - Steroid induced osteoporosis: an opportunity for prevention? AB - OBJECTIVE: To determine the frequency with which osteoporosis prophylaxis is given to corticosteroid treated hospital inpatients. METHODS: All patients receiving systemic corticosteroids in a large teaching hospital over a three month period were identified through routine prescription monitoring by hospital ward pharmacists. Coprescription of antiosteoporotic therapy was recorded, along with other relevant details such as steroid dose, actual, or intended duration of therapy, and indication for therapy. RESULTS: Corticosteroids were prescribed to 214 patients over the study period, giving an average rate of 2.5 new prescriptions each day. Indications included: chest disease (n = 84; 39.2%), cancer (n = 17; 7.9%), inflammatory bowel disease (n = 16; 7.5%), rheumatoid arthritis/connective tissue disease (n = 16; 7.5%), and renal diseases (n = 7; 3.3%). One hundred and twelve patients (52.3%) were receiving short term steroid therapy (less than four months); 66 (37%) were receiving medium/long term steroid therapy (four months or more). In 36 cases (16.8%) the duration of therapy was unknown. Only 12 of the 214 patients (5.6%) received any form of osteoporosis prophylaxis. The prevalence of prophylaxis was similarly low in postmenopausal women (six of 93; 6.4%) and in patients receiving high dose long term steroid therapy (two of 25; 8%). CONCLUSIONS: Systemic corticosteroids are used frequently in hospital practice for a wide range of indications, but few patients receive co-prescription of prophylaxis against osteoporosis. This is true even in high risk groups such as postmenopausal women and those on high dose long term steroid therapy. Identification of individuals by the mechanism used in this study provides an opportunity by which all corticosteroid treated patients could be detected and offered osteoporosis prophylaxis before serious loss of bone density has occurred. PMID- 7880125 TI - Sex hormones, glucocorticoids and autoimmunity: facts and hypotheses. PMID- 7880128 TI - Antiperinuclear factor in the polyarticular form of juvenile chronic arthritis: are use of frozen material or age of patients relevant? PMID- 7880129 TI - Chronic calcifying pancreatitis in rheumatic diseases. PMID- 7880127 TI - Prevalence of beta 2-glycoprotein I antibody in systemic lupus erythematosus patients with beta 2-glycoprotein I dependent antiphospholipid antibodies. AB - OBJECTIVE: To investigate whether beta 2-glycoprotein I antibody (aGPI) exists in sera that are positive for antiphospholipid antibodies (aPL). METHODS: Thirty six patients with systemic lupus erythematosus (SLE) and 20 healthy volunteers were recruited. GPI independent and dependent aPL (anticardiolipin (aCL), antiphosphatidylserine, antiphosphatidylinositol, antiphosphatidic acid) were measured using a conventional enzyme linked immunosorbent assay (ELISA). aGPI was measured by an ELISA using a gamma irradiated plate coated with purified GPI. RESULTS: Twenty of 36 SLE patients were positive for at least one of the GPI dependent aPL. Five of these 20 were also positive for aGPI. Another five of the 20 showed low GPI dependency aCL antibodies; however, three of these patients required GPI for binding to phosphatidylserine, phosphatidylinositol, or both. CONCLUSION: We confirmed the existence of aGPI in patients with true GPI dependent aPL. From these results, we recommend the use of a gamma irradiated plate with GPI as antigen for the detection of true GPI dependent aPL or aGPI. PMID- 7880131 TI - What do experienced GPs really need in communication skills training? AB - In studying the connections between the verbal interactions in general practice consultations and outcomes such as patient and doctor satisfaction, the authors developed an interest in the various sources of occupational stress for Australian GPs. Doctors and their patients do not necessarily agree about how satisfactory a consultation was, raising questions about whose definition of quality in medical care should prevail. Doctors' concerns about exceeding the Health Insurance Commission (HIC) norms for frequency and length of consultations seemed to inhibit them from providing the listening time some patients need. Complexity of consultations proved difficult to rate reliably. Experienced GPs in a preceptor role expressed mixed feelings about the value of communication skills training compared with changes in remuneration policies. We seek comment from readers about these observations. PMID- 7880130 TI - Small bowel telangiectasia in scleroderma. PMID- 7880132 TI - Initial burn management in the primary care situation. AB - Each year more than 150,000 people in Australia and New Zealand experience burning of sufficient severity for them to seek medical help, with 400 people dying annually. Primary care involves careful identification of burn healing potential and severity of injury. Major burns are best managed by regional Burn Units. The assessment, early management and burns unit transfer indications are addressed in this article. PMID- 7880133 TI - New developments in burn management. AB - Recent understanding of the effects of topical antimicrobials on cells that heal the wound, the role of infection, and new understandings of the role of occlusive 'biological dressings' have resulted in a more rational treatment protocol for burn wounds. With improvements in the resuscitation and intensive management of severe burns, more patients survive the initial effects of the injury, resulting in developments to close a large burn wound, which include expanding the patient's own skin to cover those large areas. PMID- 7880134 TI - Contact media approach to burn scar management. AB - The introduction of contact media in burn scar management has offered a cost effective alternative to pressure garment therapy, with improvements in function and cosmesis. The range of contact media now available allows for therapy to be individualised to the patient regardless of the size and site of the scar. The application and indications for contact media are presented and the probable mode of action is briefly discussed. PMID- 7880135 TI - Childhood burns. AB - Attending to pain relief, preventing shock and infection and obtaining early skin cover with thought to subsequent scar management are the main thrusts of this article. The author also emphasises the point that prevention through education needs to be more aggressive. A detailed approach to treatment is given. PMID- 7880136 TI - Burns to the hand. AB - Hands are a common area for burns to occur. Small, superficial burns may need little medical care whereas larger, deeper burns require the services of a specialised burn team and a variety of reconstructive plastic surgical techniques to avoid long-term stiffness and minimise functional loss. PMID- 7880137 TI - Burn injuries in children. The emotional and psychological effects on child and family. AB - Attention to the total care of the patient and family is needed to promote emotional as well as physical healing. This paper looks at the grief process as experienced by the parents of a burn injured child. Mention is made of non accidental injuries, accident prevention and the rehabilitation stage of a burn injury. Emphasis is on scalds to toddlers between the ages of 1 to 2 years. PMID- 7880138 TI - A review of 5 existing guidelines for planning focus groups in GP research. AB - The use of a focus group as a research method has become increasingly common in general practice related studies. Although existing guidelines for planning focus groups are very useful, a review of these guidelines indicate that a few of them are vague and need further elaboration. The authors review five existing guidelines for planning focus groups. These are size, number, duration, format and composition of a focus group. Suggestions have been made to address the uncertainties in these areas when a focus group is used. This paper was a section of manuscript presented at the 2nd International Qualitative Health Research Conference on 11 June 1994, Hershey, Pennsylvania. PMID- 7880139 TI - The management of arthritis in general practice. Results from the Australian morbidity and treatment survey, 1990-1991. AB - Arthritis is the ninth most commonly managed problem in general practice in Australia. This paper provides an overview of its management in general practice and draws some comparisons with an earlier study. PMID- 7880140 TI - Writing a curriculum vitae, resume or data sheet. AB - This paper outlines a method for the preparation of a curriculum vitae, resume or data sheet, which is an essential document for professional people seeking employment or promotion. However, it needs to be accurate and relevant to the circumstances of the position, and requires regular updating. PMID- 7880141 TI - Treatment of infestations. PMID- 7880142 TI - Skin lesions with a chronic infection. PMID- 7880143 TI - Patient education. Viral skin rashes in children. PMID- 7880144 TI - Practice tip. Wedge resection of nail with delayed nail fold excision. PMID- 7880145 TI - Peter Stone. Medical politician and diplomat. PMID- 7880146 TI - Tangled webs. PMID- 7880147 TI - How to take a Pap smear. PMID- 7880148 TI - Infant feeding. PMID- 7880149 TI - Maintaining ethical standards. PMID- 7880150 TI - Tropical ear treatment. PMID- 7880151 TI - Effect of hilsa (Tenualosa ilisha) fish in hypercholesterolemic subjects. AB - Tenualosa ilisha is a popular, tasty fish found in the rivers of Bangladesh round the year. The fish is rich in oil which provides mainly 16:0 and 18:1 fatty acids but also a little of w-3 polyunsaturated fatty acids (w-3 PUFAs). The present study was undertaken to evaluate the effect of eating hilsa fish in hypercholesterolemic subjects. The fish was indeed found to have hypocholesterolemic effect in subjects who had hypercholesterolemia. After 10 months of eating 100g hilsa fish per day, serum total cholesterol level fell from 285.1 to 244.6 mg/dl (14.2% decrease) in the hypercholesterolemic subjects. But the difference was not statistically significant (p < 0.05). The fall in total cholesterol was exclusively due to fall in LDL-cholesterol. Serum triglyceride, serum HDL-cholesterol increased in the experimental subjects by 12.5%. On the other hand, serum total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels were not changed in control subjects. Both in control and experimental subjects there were no changes in body weight and blood pressure during the study period. The results indicate that hilsa fish, although it is fatty and contains cholesterol, but it may reduce blood cholesterol level in hypercholesterolemic subjects. PMID- 7880152 TI - Determination of negative autopsy rate at Sir Salimullah Medical College, Dhaka. AB - Two hundred and seventy four dead bodies were brought to the Forensic Medicine department of Sir Salimullah Medical College, Dhaka for the purpose of Medico legal autopsy during the period Jan '91 to Dec '91, 72.63% were male and 27.37% were female. After thorough autopsy it was found that in 19 (6.93%) cases no opinion as to the cause or nature of death could be given. PMID- 7880153 TI - Hypoglycaemic effects of Andrographis paniculata Nees on non-diabetic rabbits. AB - So far known Andrographis paniculata Nees (AP) is a hepatoprotective, antiplatelet and antithrombotic drug. In this experiment its hypoglycaemic effect has been tried in various way. Water extract of AP 10 mg/kg body weight can prevent induction of hyperglycaemia significantly (P < 0.001) induced by oral administration of glucose 2 mg/kg body weight. But any how failed to do so in adrenaline induced hyperglycaemia. It also failed to demonstrate any "fasting blood sugar lowering effect" upon chronic administration (6 weeks) of AP. So probably AP prevents glucose absorption from gut. Whole experiment was done on rabbits. PMID- 7880154 TI - Fractured tracheostomy tubes: 3 case reports. AB - Although tracheobronchial foreign bodies are not rare, fractured tracheostomy tubes presenting as such, is rare indeed. Three such cases (one metallic and two Polyvenyl Chloride (P.V.C. tubes) are reported here. These foreign bodies were removed bronchoscopically with uneventful recovery. PMID- 7880155 TI - Ralph Winfred Tyler. Born April 22, 1902--died February 18, 1994. PMID- 7880156 TI - Using a group-oriented contingency to increase social interactions between children with autism and their peers. A preliminary analysis of corollary supportive behaviors. AB - The effects of a group-oriented contingency on the social and supportive interactions of three preschoolers with autism and their socially competent peers were examined. Children participated in daily manipulative play activities in groups of three (including one target child and two peers). A group reinforcement contingency increased all three target children's social interactions with peers (e.g., share, assistance, and play organizers) but produced few or no corollary supportive exchanges within the playgroups (e.g., one socially competent youngster tells another to "Ask [target child] to share the Lego toys with us"). After a withdrawal of treatment phase in which social interactions decreased to low levels, children were taught to direct supportive comments to other members of their playgroups. Following this brief training, the interdependent group contingency was reinstated to reinforce the share, assistance, and play organizer exchanges between the target children and peers. In addition to interacting with the target children, socially competent youngsters also used supportive prompts to facilitate the social exchanges between their remaining group members. Children's social and supportive interactions decreased and increased again during subsequent baseline and group contingency phases. These results are discussed with regard to the efficacy of group-oriented contingencies and the function of supportive peer behaviors. PMID- 7880157 TI - A demonstration of generalization of performance across settings, materials, and motor responses for students with profound mental retardation. AB - A treatment package, consisting of multiple exemplar training and community-based instruction, was evaluated for its effectiveness in teaching four students with profound mental retardation and multiple disabilities to participate in two sets of community-living tasks. All training took place in community settings, and each student demonstrated improved performance on at least one task set. In addition, all students demonstrated improved performance on a series of tasks selected to assess generalization of performance across settings, materials, and/or motoric responses required to complete the target task. Maintenance of performance over a 4- to 5-month period was assessed and achieved for two of the students. The results of this investigation are discussed in terms of the implications for programming for students with profound mental retardation. PMID- 7880158 TI - Use of integrated, general education, and community settings as primary contexts for skill instruction for students with severe, multiple disabilities. AB - Four students with severe, multiple disabilities learned to use four to five new skills at critical moments within age-appropriate activities. Instruction was provided only at moments critical to the continuation of the activities when natural cues and consequences delineated the need for the target behaviors. This method of intervention was combined with a more traditional package of antecedent prompt-fade procedures and, in a few instances, time delay. The purpose of the study was to analyze the effects of instruction given only at natural critical moments on the acquisition of basic sensory, motor, social, and communication behaviors. A multiple baseline design across skills within separate activities for four participants was employed. Fifteen of 17 skills were acquired to criterion. In addition, "learning to learn" effects occurred within each activity as instruction of new target behaviors was introduced. The outcomes are important for the participant population because they document the effect of integrated educational models for teaching the most basic skills. Discussion of the motivation provided by activity routines in general education and community settings, as well as interpretation of data when participants have the most severe disabilities, is presented. PMID- 7880159 TI - Interaction of persons with severe mental retardation and their nondisabled co workers in integrated work settings. AB - This investigation matched 23 workers with severe mental retardation to 23 workers without disabilities by job type and minimal duration of employment (at least 6 months) to determine if co-worker relations differed between the two groups of employees. Results indicated that, compared to workers with severe mental retardation, nondisabled workers were more likely to receive information, to receive training, and to interact as friends outside the workplace. PMID- 7880160 TI - Individual social skills training and co-worker training for supported employees with dual sensory impairment. Two case examples. AB - Two case studies examined the efficacy of two social enhancement procedures- individual social skills training (SST) and co-worker intervention for two employees with dual sensory impairment who were working in competitive employment settings but who were socially isolated from contact with their nondisabled co workers. A variety of measures, including direct behavioral observations and social validation ratings, examined social interaction and the formation of social networks in the workplace. Results showed that the number and duration of social interactions improved with each of the social enhancement programs. Social validation data and anecdotal reports indicated that the employees with disabilities became more socially competent, interactive, and included in the social network of the workplace. Interestingly, SST followed by co-worker training resulted in greater increases in social responding as compared to co worker training followed by SST. PMID- 7880161 TI - Feedback to staff on resident lifestyle. A descriptive analysis. AB - Providing feedback has been found to affect the behavior of staff of school and community programs. The present article presents a descriptive analysis of feedback provided to staff members concerning the lifestyle of 33 participants in 18 community residential programs in Oregon. Staff from four cohorts of programs were trained to monitor the physically and socially integrated activities experienced by program participants, and to review those data at weekly meetings. Examination of the results before and after programs had used the monitoring system indicated increases in the average number of community activities experienced by participants, the average number of activities they did with community people, the size of their social networks, and the number of individuals they identified as friends. Results were discussed in terms of the role of feedback in improving community support, the need for further research for understanding staff behaviors responsible for observed gains, and the need to better understand the relationship between observed patterns of activities and individual quality of life. PMID- 7880162 TI - Search for influence of 1.5 Tesla magnetic field on growth of yeast cells. AB - We have used a clinical magnetic resonance imager to search for the possible effects of a 1.5 T magnetic fields on the growth of the yeast Saccharomyces cerevisiae. Yeast samples were grown in nutrient broth contained in constant temperature boxes, both in and out of the magnetic field of the imager. Growth was measured by using a hemocytometer and light microscope to calculate cell densities. Over the time span corresponding to approximately seven cell divisions, we find no convincing statistical evidence for an effect of magnetic field on cell density. PMID- 7880163 TI - Influence of 50 Hz electric and magnetic fields on the pulse rate of human heart. AB - This investigation studied the effects of 50 Hz electric and magnetic fields on the pulse rate of the human heart. The ECG (electrocardiograms) of 41 male volunteers were recorded with a Holter recorder. Twenty-six subjects were measured in and outside real fields, and 15 subjects were measured in and outside "sham" fields. The blood pressure and EEG (electroencephalogram) were also measured, but this article presents only the results of ECG recordings. The measurements took 3 h. The subjects were first sitting for 1 h outside the fields, then 1 h in the real or "sham" fields, and then, again, 1 h outside the fields. The electric field strength varied from 3.5 to 4.3 kV/m and the magnetic flux density from 1.4 to 6.6 microT. An analysis of the ECG recordings showed that the subjects' pulse rates were the same in and outside the fields. No response occurred when the subjects were exposed to real or "sham" fields. PMID- 7880164 TI - Circularly polarized, sinusoidal, 50 Hz magnetic field exposure does not influence plasma testosterone levels of rats. AB - We exposed rats to circularly polarized 50 Hz magnetic fields to determine if plasma testosterone concentration was affected. Previous experiments indicate that magnetic fields suppress the nighttime rise in melatonin, suggesting that other neuroendocrine changes might occur as well. Male Wistar-King rats were exposed almost continuously for 6 weeks to magnetic flux densities of 1, 5, or 50 microT. Blood samples were obtained by decapitation at 12:00 h and 24:00 h. Plasma testosterone concentration showed a significant day-night difference, with a higher level at 12:00 h when studied in July and December, but night difference, with a higher level at 12:00 h when studied in July and December, but the day-night difference disappeared when concentrations were studied in April. In three experiments, magnetic field exposure had no statistically significant effect on plasma testosterone levels compared with the sham-exposed groups. These findings indicate that 6 weeks of nearly continuous exposure to circularly polarized, 50 Hz magnetic fields did not change plasma testosterone concentration in rats. PMID- 7880165 TI - Power frequency magnetic field exposures among nurses in a neonatal intensive care unit and a normal newborn nursery. AB - Given the current interest in potential carcinogenic and developmental effects of exposure to extremely-low-frequency electromagnetic fields, there is a need to identify cohorts of exposed female workers for future epidemiologic investigations. This study was designed to test the hypothesis that nurses working in neonatal intensive care units (NICU) may be significantly exposed to power-frequency magnetic fields. An electromagnetic field monitor was used to measure magnetic fields at distances of 5, 15, 30, and 60 cm from the surfaces of each device used in the NICU. Six female nurses assigned to the NICU (the "exposed" group) and six female nurses working in the normal newborn nursery (the "referent" group) wore EMDEX dosimeters for the entire duration of their 12 h shifts. An investigator kept a detailed log of each NICU subject's whereabouts for the first one-third of her shift. Magnetic fields at 5 cm from the front (defined by the nurses' usual work area) of the NICU devices ranged from less than 0.1 to 114 microT and in all cases decreased considerably with increasing distance. The geometric mean of the shift-time-weighted average exposure of the NICU nurses was 0.17 microT compared with 0.11 microT for the normal newborn nurses. The percentage of time when subjects were exposed to magnetic fields of 0.4 microT or greater ranged from 5.8% to 15.6% for the NICU nurses, 0.4% to 2.9% for five of the comparison group nurses, and was 9.4% for one of the normal newborn nurses with unidentified aberrantly high exposures. Log data revealed that the vast majority of observed peaks among NICU nurses occurred while subjects were in close proximity to infant bed units. We conclude that NICU nurses represent one female-intensive job sector with intermittent high exposures to ELF magnetic fields and encourage larger exposure studies of nurses in a variety of medical settings. PMID- 7880166 TI - Effects of 2.45-GHz microwave radiation and phorbol ester 12-O tetradecanoylphorbol-13-acetate on dimethylhydrazine-induced colon cancer in mice. AB - The purpose of this study was to investigate the effects of 2.45 GHz microwave (MW) radiation on dimethylhydrazine (DMH)-induced colon cancer in mice. The subjects were 115 Balb/c mice 4 weeks of age. The animals were divided into group A (control), group B (DMH), group C (DMH+MW), and group D [DMH + 12-O tetradecanoylphorbol-13- acetate (TPA)]. Radiation (10 mW/cm2) was delivered dorsally with the E field parallel to the mouse's long body axis in an anechoic chamber. Radiations were administered 3 hr daily, 6 days per week, over a period of 5 months. The average SAR was estimated to be 10-12 W/kg. During the course of radiation treatments, DMH was injected once per week. The tumor promoter TPA was administered once per week for 10 weeks, from the third week on, after the initial treatment. The incidence of tumors did not significantly differ between the three test groups (groups B, C, and D; P > 0.25). However, the number of tumors, the size of the tumors, and the incidence of protuberant and infiltrative types in tumor-bearing animals were higher in group D compared to groups B and C (P < 0.05). No difference was found between groups B and C (P > 0.25). The study indicates that 2.45 GHz microwave radiation at 10 mW/cm2 power density did not promote DMH-induced colon cancers in young mice. The study also showed that TPA could accelerate colon tumor production if a tumor was initiated. PMID- 7880167 TI - Stochastic resonance as a possible mechanism of amplification of weak electric signals in living cells. AB - The most important but still unresolved problem in bioelectromagnetics is the interaction of weak electromagnetic fields (EMFs) with living cells. Thermal and other types of noise pose restrictions in cell detection of weak signals. As a consequence, some extant experimental results that indicate low-intensity field effects cannot be accounted for, and this renders the results themselves questionable. One way out of this dead end is to search for possible mechanisms of signal amplification. In this paper, we discuss a general mechanism in which a weak signal is amplified by system noise itself. This mechanism was discovered several years ago in physics and is known, in its simplest form, as a stochastic resonance. It was shown that signal amplification may exceed a factor of 1000, which renders existing estimations of EMF thresholds highly speculative. The applicability of the stochastic resonance concept to cells is discussed particularly with respect to the possible role of the cell membrane in the amplification process. PMID- 7880168 TI - Application of the radical pair mechanism to free radicals in organized systems: can the effects of 60 Hz be predicted from studies under static fields? AB - The influence of 60-Hz magnetic fields on free radical reactions can be quantitatively predicted from the knowledge of the effect of static fields on free radical behavior. Studies of radical reactions in micellar systems show that the behavior under a 60-Hz field is identical to that under a static field at any given point in time. PMID- 7880169 TI - Character of the effect of microwave on conduction velocity of frog ventricular muscle. AB - Thirty-two frog hearts were divided into four groups and placed individually in temperature-controlled waveguides filled with Ringer's solution. The pacemaker was removed, and stimulation was provided at 0.3 Hz by three carbon-loaded Teflon electrodes located on the aorta and the ventricular muscle. Conduction velocity was measured from the difference between two action potentials. One group served as control; the three other groups were exposed for 2 h to pulsed 2,450 MHz microwave fields (10 microseconds, 0.001 duty cycle, 16 Hz modulation) at specific absorption rates (SARs) of 0.003, 2, and 6 W/kg, respectively. No significant difference in conduction velocity was found between the control and the exposed groups. PMID- 7880170 TI - Design and fabrication of well confined uniform magnetic field exposure systems. AB - Exposure systems that provide good magnetic field uniformity, minimum stray fields, and minimal heating, vibration, and hum, as well as capability for true sham exposure in which current flows in the coils, are needed to determine rigorously the biological effects of weak magnetic fields. Designs based on acrylic polymer coil support structures and twisted pair bifilary coil windings were employed to fabricate several different systems for the exposure of laboratory animals and cell cultures to magnetic fields. These systems exhibit excellent performance characteristics in terms of exposure field uniformity, stray field containment, and exposure field cancellation in the sham exposure mode. A custom-written computer program was used to determine the best arrangement for coils with regard to field uniformity in the exposure volume and stray field containment. For in vivo exposures, modules were made up of four Merritt four-coil sets, built into a single structure and positioned to form an octapole with fields directed in the horizontal plane. For in vitro applications, two different coil configurations were selected to produce the vertical fields required. A quadrupole system, comprising modules consisting of two Merritt four coil sets arranged side by side to limit stray fields, was built as a prototype. In the second configuration, one Merritt four-coil set was positioned inside the other to form a concentric coil set. In both in vitro systems, exposure chambers were connected to remote commercial incubators in order to reduce ambient magnetic fields in the exposure volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880171 TI - Effects of extremely-low-frequency electromagnetic fields on ion transport in several mammalian cells. AB - We have investigated the effects of sinusoidal electromagnetic fields (EMF) on ion transport (Ca2+, Na+, K+, and H+) in several cell types (red blood cells, thymocytes, Ehrlich ascites tumor cells, and HL60 and U937 human leukemia cells). The effects on the uptake of radioactive tracers as well as on the cytosolic Ca2+ concentration ([Ca2+]i), the intracellular pH (pHi), and the transmembrane potentsial (TMP) were studied. Exposure to EMF at 50 Hz and 100-2000 microT (rms) had no significant effects on any of these parameters. Exposure to EMF of 20-1200 microT (rms) at the estimated cyclotron magnetic resonance frequencies for the respective ions had no significant effects except for a 12-32% increase of the uptake of 42K within a window at 14.5-15.5 Hz and 100-200 microT (rms), which was found in U937 and Ehrlich cells but not in the other cell types. PMID- 7880172 TI - Dielectric properties of human red blood cells in suspension at radio frequencies. AB - Dielectric properties of human red blood cells (RBCs) in suspension (hematocrit 50%) from 243 healthy persons (120 males, 123 females) were measured at 25 degrees C in a frequency range of 1-500 MHz, with a coaxial transmission line reflection method (one-side measurement). The measuring system, controlled by an IBM-PC computer, was composed of a network analyzer (HP4195A), an impedance test adapter (HP41951-61001), a coaxial line sensor, and a temperature-controlling set. The data measured revealed a statistically significant age dependence, with a critical age of about 49 years, above which permittivity and conductivity of human RBCs in suspension decreased significantly. PMID- 7880173 TI - Human exposure to magnetic fields: a comparative assessment of two dosimeters. AB - Two types of dosimeters for measuring human exposure to 60 Hz magnetic fields were compared. Fifty adults wore the single-axis, wrist model AMEX (average magnetic field exposure system) and the triple axis, hip-pocket or pouch model AMEX-3D meters for 2 days. Ninety-six percent of the tests were accomplished without apparent dosimeter failure. The average root mean square magnetic flux density measurements with the AMEX-3D (mean = 0.10 microT, S.D. = 0.07, range = 0.03-0.31) were significantly higher than with the AMEX meter (mean = 0.07 microT, S.D. 0.05, range = 0.02-0.27 microT) (t test, P < 0.01). There was substantial correlation between the AMEX and the AMEX-3D measurements (Pearson's correlation coefficient = 0.65, P < 0.01) but poor concordance (Intraclass correlation coefficient = -0.25). These results suggest that there is a wide variation in exposure to extremely low frequency magnetic fields in the population. Magnetic field measurements with the AMEX-3D are nearly always higher than with the AMEX dosimeters. Caution is advised when comparing magnetic field measurements made with different types of dosimeters. PMID- 7880174 TI - [Nonproteolytic enzymes for peptide synthesis]. AB - Use of nonproteases in peptide synthesis is reviewed for the first time. The enzymes are suggested to be classified under three groups--ATP-dependent enzymes (not assigned to ribosome system), hydrolases and oxidoreductases. PMID- 7880175 TI - [Probabilistic evaluation of homology of primary protein structures]. AB - Criteria have been developed for resemblance of segments of certain length of different proteins to be considered as an evidence of those proteins relationship. A table is formed of minimal numbers of identical amino acids for which the probability of the causal coincidence in a segment of certain length is less then 1%. The criteria were corroborated by comparison of natural proteins and model amino acid sequences concocted by means of the random numbers generator. PMID- 7880176 TI - [Preparation and characteristics of a tritiated derivative of CP-96,345--a nonpeptide antagonist of the substance P receptor with a high specific radioactivity]. AB - [3H]CP-96.345 with the specific radioactivity of 84.2 Ci/mmol has been prepared from CP-96.345 by the high-temperature solid state isotopic exchange. The tritiated compound was equipotent with the parent antagonist in inhibiting the iodinated substance P binding to brain membranes from various species. Direct binding of [3H]CP-96.345 was detected by radioligand analysis using the striatum enriched membranes from the guinea-pig brain. PMID- 7880177 TI - [Localization of the immunodominant site in the hepatitis B virus core antigen using synthetic peptides]. AB - Based on theoretical analysis of secondary structure and hydrophilicity data, the region (residues 73-89) of the HBV core-antigen presumably containing the antigenic determinant has been revealed. The epitope mapping of this region with the use of synthetic peptides, obtained by the pin technology and solid phase method, was carried out. Peptides were synthesized in two variants with different amino acids residues in the position 80 (Ala, Ile). Free peptides and their conjugates with bovine serum albumin were tested for antigenicity in ELISA. The results indicate that the fragment 78-83 is the shortest region of the core antigen which reacts with antibodies from hepatitis B patients sera. PMID- 7880178 TI - [A transformylation reaction--transfer of an N-formyl residue to amino acids and peptides in nucleophilic groups--as a side reaction of peptide synthesis]. AB - The formyl group transfer from N-formyl amino acids and their derivatives to other acceptors--amino acids esters and aniline, was studied. Formylamino acids with the free alpha-carboxyl group are more effective donors in transformylation than formyl peptides or esters of formylamino acids. PMID- 7880179 TI - [Highly-sensitive nonradioactive detection of the tick-borne encephalitis virus]. AB - The non-radioactive reverse dot-blot method was used for the detection of tick borne encephalitis virus (TBEV) in clinical specimens. The method involves reverse transcription (RT) and polymerase chain reaction (PCR) using a pair of biotin-labelled oligonucleotide primers. These primers flank a region in the gene of the envelope protein E, which is more conserved than other regions, and initiate the polymerisation with RNAs of all the investigated strains. The amplified cDNA was captured from solution on a solid support using complementary oligonucleotides covalently bound to a polyamide membrane. The biotin labels of the resulting hybrids were visualized by means of the streptavidin-horseradish peroxidase conjugate. The detection limit of the test was about 10(3)-10(4) molecules of target RNA. The sensitivity was comparable to that obtained by dot hybridization of PCR-product with 32P-labelled DNA probe. The method was used for the detection of RNA in specimens of tick and blood. PMID- 7880180 TI - [Features of replicating synthetic oligonucleotides with non-native chains]. AB - The in vitro replication of synthetic oligodeoxyribonucleotides carrying internucleotide polyphosphate groups or alkanediol "spacers" of various sizes with the use of various DNA polymerases has been studied. All modifications, except for the diphosphate group, almost completely block the polymerization process. In the case of AMV reverse transcriptase, Taq and T7 DNA polymerases and also the Klenow fragment of E. coli DNA polymerase I, a template-independent addition of a nucleotide at the 3' end of the incomplete replica was observed. T4 DNA polymerase, displaying the strongest 3'-5' exonuclease activity among the polymerases studied, did not incorporate additional nucleotides. The use of oligonucleotides with non-nucleotide inserts as primers in polymerase chain reaction (PCR) allows to obtain DNA copies with protruding 5'-termini, suitable for hybridisation analysis. PMID- 7880181 TI - [Interaction of RNAase H from E. coli with modified hybrid duplexes. I. Duplexes modified at the carbohydrate residue]. AB - The influence of oligodeoxyribonucleotide probes containing 1-(D-beta-2' deoxythreo-pentofuranosyl)thymine or 1-(D-beta-2'-deoxy-2'-fluoro pentofuranosyl)uracil on the ability of the hybrid duplexes to interact with RNase H from E. coli was studied. A kinetic approach was used to measure of the modification effect. The hybrid duplex, prA18/d(TTflU)6TT, was shown not to interact with RNase H, whereas prA18/d(xTTT)6 inhibited the RNase H activity (Ki = 0.67 mkM). The thermostability of the modified duplexes was estimated. The present technique may lead to the use of some modified oligonucleotides as antisences. PMID- 7880182 TI - Some thoughts on autoimmunity. PMID- 7880183 TI - Receptors for immunoglobulin G. Molecular diversity and implications for disease. AB - Our knowledge about human Fc gamma receptors has increased dramatically within the last several years. Their structural diversity presents a rich framework within which to understand how immunoglobulins and immunoglobulin complexes activate such a broad range of cell programs relevant to autoimmune diseases. Alleles of Fc gamma receptors provide a new perspective within which to define the interplay between the qualitative and quantitative humoral immune response and host genotype and to identify heritable risk factors for disease susceptibility. With recent insights into the role of Fc gamma receptors in the pathophysiology of inflammatory lesions, we can also anticipate important advances in therapeutic intervention. PMID- 7880184 TI - Rheumatoid arthritis from a student's perspective. PMID- 7880185 TI - The total costs of drug therapy for rheumatoid arthritis. A model based on costs of drug, monitoring, and toxicity. AB - OBJECTIVE: We created a model to estimate the total medication costs of treating patients with rheumatoid arthritis with 6 second-line agents for the first 6 months of treatment. METHODS: Drug costs were obtained from a survey of pharmacies; monitoring costs were calculated from utilization information obtained in a survey of rheumatologists; toxicity costs were obtained using decision trees to represent the evaluation and treatment of potential toxicities. Monitoring and toxicity costs were estimated using costs from the Boston University Medical Center or, for hospitalizations, using appropriate diagnosis related group categories. The sum of the 3 components determined the total medication costs. RESULTS: The least expensive medication was penicillamine, at $10.62/week, and the most expensive was injectable gold, at $30.89/week. In terms of monitoring costs, methotrexate had the highest costs associated with necessary laboratory tests and office visits. Hydroxychloroquine had the lowest monitoring costs for office visits, and oral gold had the lowest for laboratory costs. Hematologic toxicities were the largest component of toxicity costs for all 6 medications, and renal toxicities were costly for patients taking oral gold, penicillamine, and injectable gold. Total medication costs revealed oral gold as the least expensive medication and injectable gold as the most expensive. The combination of monitoring and toxicity costs accounted for more than 60% of the total costs for all medications except injectable gold. In all cases, the cost of treating toxicities was the smallest of the 3 components. CONCLUSION: When calculating the costs of drug therapy, it is important to consider not only the price of the drug, but also the costs of monitoring and treating the toxicities that might occur. Failure to do so will result in underestimating the true costs of treatment with these medications. PMID- 7880186 TI - The cost-effectiveness of liver biopsy in rheumatoid arthritis patients treated with methotrexate. AB - OBJECTIVE: To assess the cost-effectiveness of liver biopsy in monitoring rheumatoid arthritis (RA) patients for methotrexate (MTX)-induced cirrhosis. METHODS: A decision analytic model was used to compare a strategy of no biopsy versus strategies of biopsy after 5 years or 10 years of MTX treatment. RESULTS: Biopsy after 5 years of MTX treatment had a cost-effectiveness ratio of $1,891,830 per year of life saved, while biopsy after 10 years of treatment had a cost-effectiveness ratio of $52,374 per year of life saved. Sensitivity analyses revealed that the cost-effectiveness of biopsy was most dependent on the probability of cirrhosis. CONCLUSION: Liver biopsy to monitor for MTX-induced cirrhosis in RA patients is not cost effective after 5 years of treatment, and even biopsy after 10 years has a high cost. PMID- 7880187 TI - Prednisone treatment of elderly-onset rheumatoid arthritis. Disease activity and bone mass in comparison with chloroquine treatment. AB - OBJECTIVE: Prednisone is frequently used in the treatment of elderly-onset rheumatoid arthritis (RA), but the balance between efficacy and toxicity, including the effect on bone mass, has not been investigated in long-term studies. This prospective, randomized study was undertaken to compare disease activity and bone mass during long-term treatment with prednisone versus chloroquine in this patient population. METHODS: Patients with active RA diagnosed at age > or = 60 were randomized to receive prednisone (15 mg/day for 1 month, with the dosage tapered as low as possible thereafter) (n = 28) or chloroquine (n = 28). Patients who did not show a response received other second line drugs as an adjunct to prednisone or as a replacement for chloroquine. Bone mass was measured by dual-energy x-ray absorptiometry. The study duration was 2 years. RESULTS: During the 2 years, treatment with other second-line drugs was needed for 12 patients in the prednisone group (43%) and 8 in the chloroquine group (29%). Functional capacity and disease activity improved significantly in both groups and did not differ significantly between the groups, except for a greater improvement in the prednisone group at 1 month. Radiographic scores for joint destruction progressed similarly in both groups. There was a nonsignificant excess bone loss of 1.8% in the spine and 1.5% in the hip in the prednisone group, compared with the chloroquine group. CONCLUSION: Neither treatment was entirely satisfactory since a significant number of patients needed an additional second-line drug over the 2-year period. PMID- 7880188 TI - The determinants of walking velocity in the elderly. An evaluation using regression trees. AB - OBJECTIVE: To determine predictors of walking velocity in the elderly. METHODS: Five hundred thirty-two persons from 3 cohorts of elderly persons (retirement community, ambulatory care medical clinic, or chronically homebound population) performed a 10-foot (for the homebound subjects) or 50-foot (for all other subjects) walk time test and underwent a standardized interview, chart review, and clinical examination. The 73 independent variables that were evaluated included demographic, musculoskeletal, neurologic, psychologic, and other comorbidity items. Least-squares and least-absolute-deviation regression tree analyses were performed to determine the strongest predictive factors associated with walking velocity. RESULTS: Sampling cohort (homebound versus non-homebound), quadriceps strength, hip flexion strength, lumbosacral spine impairment, lower joint impairment, and education were found to be associated with walking velocity. Joint pain measures were not associated with walking velocity. CONCLUSION: Muscle strength variables are better predictors of walking velocity than are joint pain variables. Thus, clinical trials and observational studies using walking velocity as an outcome need to take into consideration the influence of muscle strength on this outcome variable. PMID- 7880189 TI - Guidelines for clinical trials in systemic sclerosis (scleroderma). I. Disease modifying interventions. The American College of Rheumatology Committee on Design and Outcomes in Clinical Trials in Systemic Sclerosis. AB - OBJECTIVE: To develop guidelines for therapeutic trials designed to improve the overall course of systemic sclerosis (SSc), that is, to reduce the development of significant organ damage or death. METHODS: A committee developed general guidelines for patient inclusion and exclusion criteria, randomization, blinding of patients and physicians, controls, duration of the trial, investigator training, responses, samples size, study dropouts, statistical analyses, data management, and safety monitoring. Delphi and nominal group techniques were used. RESULTS: Briefly, patients with diffuse cutaneous SSc of less than 24 months' duration should be included because they are at greatest risk for the development of severe organ damage and death. Patients should be excluded if they have other connective tissue diseases, SSc-like illnesses related to exposures or ingestions, severe existing internal organ damage, an unacceptable risk of side effects, or concurrent therapies that might independently influence the outcome. Randomized, double-blind, placebo-controlled trials are preferred. The treatment and followup period must be long enough to permit observation of any disease modification, which is likely to require 18-36 months, unless an extraordinarily effective therapy is identified. Responses selected should be quantitative, consistently and accurately reflect activity of SSc in major target organs (not solely the skin), be sensitive to change, and be standardized, with limited variability. An example of a set of responses is given. Surrogate responses are desirable, but none have been validated as correlating with organ damage. CONCLUSION: Guidelines have been established for trials of disease-modifying interventions in SSc. These guidelines will need to be altered as additional information becomes available. Any given protocol will be individualized based on the nature of the intervention and objectives of the study. Nonetheless, each study team should develop a protocol that meets the spirit of these guidelines. PMID- 7880190 TI - Lyme arthritis in European children and adolescents. The Pediatric Rheumatology Collaborative Group. AB - OBJECTIVE: To evaluate and describe Lyme arthritis in European children and adolescents. METHODS: This was a prospective multicenter study. The diagnosis of Lyme arthritis required the exclusion of other diseases and positive findings on serology for IgG antibodies to Borrelia burgdorferi. Enzyme-linked immunosorbent assay, immunoblotting, and polymerase chain reaction techniques to identify infection by B burgdorferi were used. RESULTS: Among 62 children and adolescents with Lyme arthritis, only 1 had a preceding erythema migrans. Arthritis was episodic in 62% and was chronic at onset in 18%. The most common manifestation was monarthritis of the knee. Joint involvement in patients with oligoarthritis was predominantly unilateral or symmetric. Arthralgia was very rare. Treatment with 1 or 2 courses of different antibiotics resulted in disappearance of the arthritis in 77% of the patients. CONCLUSION: The clinical presentation of Lyme arthritis in children is different from that in adults. The calculated incidence of Lyme arthritis in persons under the age of 17 years (4/100,000) exceeds previous estimations. PMID- 7880191 TI - Epidemiology of polymyalgia rheumatica in Olmsted County, Minnesota, 1970-1991. AB - OBJECTIVE: To determine the incidence, prevalence, and survival of polymyalgia rheumatica (PMR) over a 22-year period in Olmsted County, Minnesota. METHODS: Using the unified record system at the Mayo Clinic for the Olmsted County population, we reviewed all medical records with a diagnosis of PMR from 1970 through 1991. RESULTS: There were 245 (173 female; 72 male) incidence cases of PMR between 1970 and 1991. The average annual age- and sex-adjusted incidence of PMR per 100,000 population > or = 50 years was 52.5 (95% confidence interval [CI] 45.9-59.2), with a significantly higher incidence in females (61.7; 95% CI 52.3 71.2) than in males (39.9; 95% CI 30.7-49.2). The incidence varied over the period of observation, but no significant trends were found. The prevalence of PMR among persons > or = 50 years on January 1, 1992 was 6/1,000. There was a small but significantly increased survival rate among male PMR patients compared with the general population. CONCLUSION: Our data demonstrate that PMR is a common nonfatal disease in the elderly, the incidence and clinical manifestations of which have varied but remained relatively stable over the last 2 decades. PMID- 7880192 TI - Correlation between infection and the onset of the giant cell (temporal) arteritis syndrome. A trigger mechanism? AB - OBJECTIVE: To assess for a correlation between infection and the onset of the giant cell (temporal) arteritis (GCA) syndrome. METHODS: A matched case-control study design was used. Records of 100 patients with biopsy-proven GCA and 100 patients undergoing corrective surgery for hip fracture who did not have GCA were retrospectively reviewed. Non-GCA patients were sex-matched with GCA patients and were as old or older in age. The review period for GCA patients was up to 4 months before and during the occurrence of symptoms (median 2 months), and for non-GCA patients, it was up to 7 months before hip fracture. The prevalence of infection was compared using matched-pairs odds ratios and their 95% confidence intervals. RESULTS: Infections were 3 times more likely to occur in GCA patients than in non-GCA patients (P < 0.05). CONCLUSION: A correlation between the occurrence of infection and the onset of GCA is strongly suggested. We speculate that infection may act as a trigger mechanism in the pathogenesis of this syndrome. PMID- 7880193 TI - Occurrence of ankylosing spondylitis in a nationwide series of twins. AB - OBJECTIVE: To obtain information on the rate of concordance for ankylosing spondylitis (AS) in a population-based series of twins. METHODS: AS cases were identified by record linkage of the population-based Finnish Twin Cohort and the nationwide registry for fully reimbursed medications. A clinical examination was performed to establish concordance for AS. RESULTS: There were 6 monozygotic (MZ) pairs and 20 dizygotic (DZ) pairs with at least 1 member affected by AS. Three MZ pairs and 3 DZ pairs were concordant for the disease. All affected subjects were HLA-B27 positive. The pairwise concordance rate was 50% in MZ twins and 20% in HLA-B27 positive DZ twins (95% confidence intervals 11.8-88.2% and 4.3%-48.1%, respectively). CONCLUSION: These results indicate that AS disease expression is largely, but not entirely, genetically based, with a gene or genes other than B27 probably playing a role. PMID- 7880194 TI - Selective induction of IgM rheumatoid factors by CD14+ monocyte-lineage cells generated from bone marrow of patients with rheumatoid arthritis. AB - OBJECTIVE: To determine the capacity of CD14+ monocyte-lineage cells induced from bone marrow of rheumatoid arthritis (RA) patients to stimulate the production of IgM rheumatoid factor (IgM-RF), in order to explore the functional abnormalities of CD14+ cells and gain insight into the mechanism of selective synthesis of IgM RF in RA. METHODS: CD14+ cells were induced by granulocyte-macrophage colony stimulating factor (GM-CSF) stimulation of CD14- cells purified from bone marrow cells obtained from 6 RA patients and 6 osteoarthritis (OA) patients. The production of IgM and IgM-RF was induced by stimulating B cells from normal healthy individuals with immobilized anti-CD3-activated autologous CD4+ T cells. The effects of CD14+ cells on the proportion of IgM-RF to total IgM produced by the normal B cells were assessed. RESULTS: CD14+ cells induced by GM-CSF stimulation of bone marrow CD14- cells from the 6 RA patients significantly enhanced the proportion of IgM-RF to total IgM produced by anti-CD3-activated CD4+ T cell-stimulated normal B cells (P < 0.05), whereas GM-CSF-induced CD14+ cells from the bone marrow of the 6 OA patients did not significantly affect IgM RF production. CD14+ cells induced by GM-CSF obtained from different sites in the same RA patient on different occasions consistently enhanced the proportion of IgM-RF to IgM produced by B cells from different normal subjects. CONCLUSION: These results indicate that abnormal CD14+ monocytes stimulate RF-producing B cells to be ready to be activated by the signals delivered through noncognate T-B interactions with anti-CD3-activated T helper cells. Moreover, the data suggest that the accelerated generation of such functionally abnormal CD14+ cells from bone marrow precursors might play an important role in the pathogenesis of RA. PMID- 7880195 TI - The role of the immunoglobulin heavy chain in human anti-DNA antibody binding specificity. AB - OBJECTIVE: To investigate the structural basis for DNA binding of the natural human IgM lambda monoclonal antibody KIM4.6. METHODS: An IgM lambda, non-DNA reactive variant hybridoma was derived during in vitro subcloning of the anti-DNA antibody KIM4.6. The variable (V)-region heavy (H) and light (L) chain genes expressed by the variant hybridoma were amplified by polymerase chain reaction, cloned, sequenced, and compared with those of the KIM4.6 parent and other DNA binding and non-DNA-binding antibodies. RESULTS: The VL chain of the variant was identical to that of KIM4.6. In contrast, the VH chain was completely different from the VH chain of the parent but was similar or identical, except in the diversity (D) and joining regions, to the VH chain of the systemic lupus erythematosus (SLE) IgG anti-DNA antibody T14 and SLE IgM nephritogenic anti-DNA antibodies NE-1 and NE-13. CONCLUSION: The expression of the KIM4.6 VL chain is not sufficient for DNA specificity. The VH chain and its D region play a key role in conferring DNA binding of the KIM4.6 anti-DNA antibody. PMID- 7880198 TI - Severe anemia as the presenting manifestation of giant cell arteritis. AB - Giant cell (temporal, cranial) arteritis (GCA) is usually confirmed in patients presenting with classic features. Those who present with atypical features often undergo prolonged evaluations until a diagnosis is established. Severe anemia as an initial manifestation of GCA has rarely been described. We describe herein 2 patients with biopsy-proven GCA who presented with severe anemia and significant weight loss, which corrected after corticosteroid therapy. PMID- 7880197 TI - Excessive function of peripheral blood neutrophils from patients with Behcet's disease and from HLA-B51 transgenic mice. AB - OBJECTIVE: To elucidate the role played by HLA-B51 in the neutrophil hyperfunction of Behcet's disease, we determined the superoxide production by purified peripheral blood neutrophils from Behcet's disease patients, from HLA B51 positive healthy individuals, and from HLA-B51 transgenic mice. METHODS: Neutrophil function was evaluated by flow cytometric analysis, detecting the conversion of 2',7'-dichlorofluorescin diacetate into dichloroflurescein, induced by superoxide in the neutrophils. RESULTS: A significant correlation between the neutrophil hyperfunction and the possession of HLA-B51 phenotype, regardless of the presence of the disease, was observed in humans. FMLP-stimulated neutrophils (without in vitro priming) from HLA-B51 transgenic mice, but not those from HLA B35 transgenic mice or from nontransgenic mice, produced substantial amounts of superoxide. CONCLUSION: The HLA-B51 molecule itself may be responsible, at least in part, for neutrophil hyperfunction in Behcet's disease. PMID- 7880196 TI - Increased insulin-like growth factor 1 production by human osteoarthritic chondrocytes is not dependent on growth hormone action. AB - OBJECTIVE: To investigate insulin-like growth factor 1 (IGF-1) production in normal and osteoarthritis (OA) chondrocytes and to further examine the role of growth hormone (GH) in adult human cartilage and, in particular, in diseased tissue. METHODS: IGF-1 production was measured with a radioimmunoassay. Binding assay, Northern blot, and reverse transcriptase polymerase chain reaction (RT PCR) techniques were used for GH receptor (GHR) detection. The biological response to GH was estimated via IGF-1 production. RESULTS: We observed that basal levels of IGF-1 production were significantly higher in OA chondrocytes than in normal cells (P < 0.005). Adult human chondrocytes, however, were unresponsive to GH stimulation with regard to IGF-1 production, as shown in dose response (0-1,000 ng/ml) and time-course (days 1-8) studies. In addition, no specific 125I-GH binding was detected in either cell type. Northern blot analysis revealed a 5.5-kb GHR messenger RNA (mRNA) species, but semiquantitative RT-PCR revealed no difference in GHR mRNA expression by normal and OA chondrocytes. CONCLUSION: This study indicates that the elevated synthesis of IGF-1 by adult human OA chondrocytes occurs through a GH/GHR-independent mechanism, suggesting that other factors are capable of controlling local IGF-1 production in these cells. PMID- 7880199 TI - Polymyositis, pulmonary fibrosis, and hepatitis C. AB - Polymyositis has been associated with several viral infections, and a spectrum of immune-related diseases may occur with hepatitis C virus (HCV) infection. Both polymyositis and HCV infection may be accompanied by interstitial lung disease; however, no association between polymyositis and HCV infection has been reported previously. We report a new association in a patient with HCV infection: anti-Jo 1 positive polymyositis and interstitial lung disease. PMID- 7880200 TI - Bullous rash and brown urine in a systemic lupus erythematosus patient treated with hydroxychloroquine. PMID- 7880201 TI - Hydroxychloroquine and pain thresholds. PMID- 7880202 TI - Acute posterior multifocal placoid pigment epitheliopathy in a patient with systemic-onset juvenile rheumatoid arthritis: treatment with cyclosporin A and prednisone. PMID- 7880203 TI - Features of male versus female patients undergoing surgery for osteoarthritis: comment on two recent articles. PMID- 7880204 TI - Diagnosis of arthritis by primary care providers versus rheumatologists: comment on the article by Chan et al. PMID- 7880206 TI - We got them elected. Now what? PMID- 7880205 TI - Hemorheology and fistula function in home hemodialysis patients following erythropoietin treatment: a prospective placebo-controlled study. AB - The beneficial effect of correcting anemia in end stage renal failure using recombinant human erythropoietin (rHuEPO) is sometimes complicated by thrombosis of the arteriovenous fistula. This placebo-controlled study investigated the relationship between hemorheological changes caused by rHuEPO and alterations in fistula function and heparin requirements in home hemodialysis patients. Erythropoietin induced a rise in high shear rate blood viscosity, a determinant of blood flow in large vessels. Doppler assessment of brachial artery blood flows, tests of fistula function and heparin requirements were similar in the two patient groups. These findings indicate that rHuEPO treatment of renal anemia resulted in the expected rise in red blood cell mass and blood viscosity although these changes did not cause problems with arteriovenous access or alter fistula function in the short term. PMID- 7880207 TI - Prevalence and prevention of glove perforation during cardiac operations. PMID- 7880208 TI - Calculating effect sizes for meta-analysis: the case of the single case. AB - This paper reviews methods for deriving measures of effect for interrupted time series (single case) designs. Limitations of prior models are described. Modifications of a regression approach developed by Center, Skiba, and Casey (1985-86, Journal of Special Education, 19, 387-400) which can simultaneously account for treatment effects on level and slope while controlling for effects of trend are advocated and a step-by-step computational algorithm is provided. The primary modification entails computing the initial estimate of trend only on baseline data. Implementation of the method with various forms of single case designs is described. PMID- 7880209 TI - Use of pentoxifylline in the treatment of cerebral malaria. PMID- 7880210 TI - [Percutaneous nephropexy]. AB - We present a new, minimally invasive method for the treatment of nephroptosis. We are suggesting the more spreaded use of this method after the good results we found during the long term observation of our 40 patients with percutaneous nephropexy. PMID- 7880211 TI - Parathyroid hormone-related protein as a tumour marker in humoral hypercalcaemia associated with occult malignancy. AB - The tumour-derived factor PTH-related protein (PTHRP) is the primary humoral factor responsible for hypercalcaemia in patients with solid tumours. In a woman presenting with anaemia and hypercalcaemia, the finding of raised plasma PTHRP and undetectable serum PTH concentrations led to further investigations and the subsequent identification of a uterine tumour. No evidence of tumour spread was found at operation, and removal of the tumour resulted in normalization of both serum calcium and plasma PTHRP. Expression of PTHRP by the tumour was shown by immunohistochemistry and in situ hybridization. We conclude that the identification of an occult tumour in a patient with hypercalcaemia and raised plasma PTHRP provides evidence of the diagnostic utility of PTHRP immunoassays in the investigation of patients with hypercalcaemia and suspected malignancy. PMID- 7880212 TI - Radio frequency eddy current losses for an annular conductor in MRI: theory and applications. AB - A theoretical derivation of the equivalent loading resistance of an annular volume conductor within a magnetic resonance imaging radio frequency (RF) coil is presented. Theoretical predictions of the magnitude of the load resistance agree well with measurement over a range of frequencies. The loading resistance is proportional to the sample conductivity, the frequency and coil sensitivity squared, and depends strongly upon the sample dimensions. The orientation of the magnetic vector potential for the specific coil geometry is also important. An experimental comparison of loading by annular and cylindrical objects with the human head over the imaging frequency range is made. Cylindrical test objects are adversely affected by the skin effect. The optimum means of simulating RF induced losses for quality assurance and performance evaluation is discussed in the light of these results. PMID- 7880213 TI - Current trends in the usage of the Adaptability Rating for Military Aviation (ARMA) among USAF flight surgeons. AB - The Adaptability Rating for Military Aviation (ARMA) is that portion of the initial flight physical that assesses an aviator candidate's motivation for and potential adaptability toward an aviation career. A survey was mailed to all USAF operational flight surgeons in the continental U.S. to describe the frequency and distribution of ARMA usage and attitudes. Descriptive statistics suggest that the ARMA is used suboptimally in accordance with current USAF regulation. ARMA training, flight surgeon satisfaction and lack of regulation clarity are described and discussed. More flight surgeons are dissatisfied with the ARMA than are satisfied, and the regulation is perceived as unclear in the area of final disposition for candidates with equivocal ARMA's. A post-hoc analysis to rule out the influences of rank, gender, experience and residency training was performed. Residency training in Aerospace Medicine is beneficial in terms of doing an ARMA, when required, and covering recommended areas. Females and those with less than 1 year experience perform an ARMA more frequently than males and experienced flight surgeons. Despite the limitations of the current ARMA, it should not be abandoned. Recommendations to improve it are provided. Doing better ARMA's can lead to decreased illness, injury, accidents, and attrition. PMID- 7880214 TI - Preventing complications of laparoscopy. PMID- 7880216 TI - Geriatric rehabilitation: what do physicians know about it and how should they use it? PMID- 7880215 TI - Nitrous oxide-isoflurane anesthesia causes more cerebral vasodilation than an equipotent dose of isoflurane in humans. AB - To compare the cerebral vascular and metabolic effect of an isoflurane-nitrous oxide mixture to an equipotent dose of isoflurane at 1.1 minimum alveolar anesthetic concentration (MAC), and to study the interaction between nitrous oxide and isoflurane anesthesia, we measured right middle cerebral artery blood flow velocity (V mca) and cerebral arteriovenous oxygen content difference (AVDO2) in six healthy patients during normocapnia and normothermia under the following sequence of steady-state anesthetic conditions: Condition A, 0.5 MAC of isoflurane, Condition B, 0.5 MAC of isoflurane + 0.6 MAC of N2O, Condition C, 1.1 MAC of isoflurane + 0.6 MAC of N2O, and Condition D, 1.1 MAC of isoflurane. The study entry sequence was randomized. V mca and AVDO2 during 1.1 MAC of isoflurane (Condition D) was 48 +/- 7 cm/s and 3.9 +/- 0.6 vol%, respectively. Substituting 0.6 MAC of isoflurane with an equipotent concentration of N2O (Condition B) resulted in an increase in both V mca and AVDO2 of approximately 20% (P < 0.05). These findings suggest that the increase in flow was accompanied by an even greater increase in metabolic rate. Adding 0.6 MAC of N2O to 1.1 MAC of isoflurane (Condition C) also increased V mca (P < 0.05). We conclude that N2O is a more potent cerebral vasodilator than an equipotent dose of isoflurane alone in humans. PMID- 7880218 TI - Association of apolipoprotein E E4 with vascular dementia. PMID- 7880217 TI - Temporal trends (1975 through 1990) in the incidence and case-fatality rates of primary ventricular fibrillation complicating acute myocardial infarction. A communitywide perspective. AB - BACKGROUND: As part of a population-based study of acute myocardial infarction, we examined changes over time in the incidence and in-hospital case-fatality rates of primary ventricular fibrillation complicating acute myocardial infarction. METHODS AND RESULTS: Patients with validated acute myocardial infarction hospitalized at 16 hospitals in the Worcester, Mass, metropolitan area between 1975 and 1990 comprised the study sample. During the 15-year study period, 5.1% of patients developed primary ventricular fibrillation in the setting of uncomplicated acute myocardial infarction, with this rate remaining relatively constant over time. Both age- and multivariable-adjusted analyses showed no significant trend in the incidence rates of primary ventricular fibrillation during the study period. The in-hospital case-fatality rate for patients with primary ventricular fibrillation was significantly elevated compared with the rate for those without primary ventricular fibrillation and uncomplicated acute myocardial infarction (48.3% versus 1.5%, P < .001). No significant change over time was noted in in-hospital case-fatality rates associated with primary ventricular fibrillation while controlling for a variety of short-term prognostic factors. CONCLUSIONS: The results of this communitywide observational study suggest that neither the incidence nor the prognosis associated with primary ventricular fibrillation resulting from acute myocardial infarction has improved over time. PMID- 7880219 TI - Gianotti-Crosti syndrome and human immunodeficiency virus infection. AB - BACKGROUND: Patients with Gianotti-Crosti syndrome (GCS) present with a distinctive self-limiting acral papular or papulovesicular eruption associated with an underlying viral illness. Gianotti-Crosti syndrome in patients infected with human immunodeficiency virus has not been previously reported. OBSERVATIONS: We report on two children infected with human immunodeficiency virus who had GCS. Both patients had clinical and histopathologic findings characteristic of GCS. The first patient had evidence of prior infection with cytomegalovirus, without evidence of active viral illness. The second patient had evidence of subclinical infection with cytomegalovirus, positive hepatitis C antibody, and active infection with Mycobacterium avium-intracellulare at the time the skin eruption began. CONCLUSIONS: We call attention to a previously unreported skin eruption, GCS, in the setting of human immunodeficiency virus infection and emphasize that determining the etiologic factors for human immunodeficiency virus-associated GCS will be difficult; such patients will probably have a variety of clinical and subclinical infections that complicate this issue. PMID- 7880220 TI - Carpal tunnel syndrome: a practical review. AB - Carpal tunnel syndrome is the most common focal entrapment syndrome. Forceful repetitive activity and vibration may be important workplace risk factors for carpal tunnel syndrome. Although systematic study has suggested that carpal tunnel syndrome is work-related, no clear "dose-response" curve has been found between the amount or severity of work and the incidence or severity of the syndrome. Nocturnal pain is a hallmark of the syndrome, and Phalen's test, the carpal compression test and the Flick test are useful indicators of the diagnosis. The most commonly used confirmatory test is the nerve conduction study, with or without electromyography. The primary care physician can treat many cases successfully with simple ergonomic modifications, splinting and steroid injections. Surgical therapy is reserved for recalcitrant cases and patients with more severe nerve impingement. In addition to traditional open procedures, carpal tunnel release may be performed endoscopically. PMID- 7880221 TI - The importance of placebo effects in pain treatment and research. AB - OBJECTIVE: To estimate the importance and implications of placebo effects in pain treatment and research from the existing literature, with emphasis on their magnitude and duration, the conditions influencing them, and proposed explanations. DATA SOURCES: English-language articles and books identified through MEDLINE (1980 through 1993) and PsycLIT (1967 through 1993) database searching, bibliography review, and expert consultation. STUDY SELECTION: Articles were included if they pertained to the review objectives. RESULTS: Placebo response rates vary greatly and are frequently much higher than the often cited one third. Placebos have time-effect curves, and peak, cumulative, and carryover effects similar to those of active medications. As with medication, surgery can produce substantial placebo effects, and this possibility is commonly overlooked in case series reports on back surgery. Individuals are not consistent in their placebo responses, and a placebo-responder personality has not been identified. Models advanced to explain placebo effects emphasize the role of anxiety, expectations, and learning. CONCLUSIONS: Placebo effects influence patient outcomes after any treatment, including surgery, that the clinician and patient believe is effective. Placebo effects plus disease natural history and regression to the mean can result in high rates of good outcomes, which may be misattributed to specific treatment effects. The true causes of improvements in pain after treatment remain unknown in the absence of independently evaluated randomized controlled trials. PMID- 7880222 TI - Would Machiavelli now be a better guide for doctors than Hippocrates? PMID- 7880223 TI - Screening for ocular toxicity in asymptomatic patients treated with tamoxifen. AB - Tamoxifen is an antiestrogen drug used in the treatment of patients with breast cancer that is being studied for use in patients at high risk for developing breast cancer. Case reports have documented ocular toxicity caused by tamoxifen in patients with visual symptoms. We attempted to determine the prevalence of ocular toxicity in visually asymptomatic tamoxifen-treated patients. We performed extensive ocular examinations on 135 visually asymptomatic tamoxifen-treated patients. Two patients (1.5%) had intraretinal refractile crystals consistent with tamoxifen retinopathy. Both patients were without visual symptoms or visual loss. Corneal crystals, macular edema, and optic nerve changes were absent. The cumulative tamoxifen doses of these two patients were 10.9 and 21.9 g, respectively. For the 135 patients studied, the mean cumulative dose was 17.2 g, with a standard deviation of 13.0. We do not believe the relatively uncommon finding of tamoxifen-related ocular toxicity merits special screening for such disease. PMID- 7880224 TI - Dilutional hyponatremia during endoscopic curettage: the "female TURP syndrome"? PMID- 7880225 TI - Medical treatment for stroke prevention. AB - PURPOSE: To review the effectiveness of medical treatments for stroke prevention in patients at elevated risk for stroke. DATA SOURCES: English-language articles published after 1977 and indexed in MEDLINE under the following Medical Subject Heading terms: anticoagulants, aspirin, dipyridamole, ticlopidine, or sulfinpyrazone, combined with cerebrovascular disorders. STUDY SELECTION: Randomized controlled trials of anticoagulant or platelet antiaggregant treatment reporting subsequent stroke and myocardial infarction, death, or complications in persons with asymptomatic carotid stenosis or bruit, transient ischemic attack (TIA), previous stroke, nonvalvular atrial fibrillation, or other vascular diseases. DATA EXTRACTION: Of 900 articles identified, 33 were selected by two independent reviewers and abstracted for outcome events and person-years of follow-up. RESULTS: In patients with nonvalvular atrial fibrillation, warfarin is highly effective in reducing stroke and death but may result in more complications. Aspirin appears to be less effective and less risky than anticoagulation. In patients with TIA or minor stroke, both aspirin and ticlopidine reduce the risk for stroke. In patients who have had myocardial infarction, warfarin is effective but had high complication rates in the reviewed studies. Aspirin slightly reduces the risk for stroke. CONCLUSIONS: Warfarin is strongly recommended for persons with nonvalvular atrial fibrillation who are older than 60 years or who have additional risk factors for stroke. Aspirin is recommended for persons at elevated risk for bleeding while receiving anticoagulants. For persons with TIA or minor stroke, aspirin should be used first. Patients who do not respond to or tolerate aspirin or who have had a major stroke are reasonable candidates for ticlopidine. For patients who have had myocardial infarction, aspirin is recommended for the prevention of secondary myocardial infarction but not of stroke. PMID- 7880226 TI - Continuing medical education needs of rural GPs in South Australia. AB - The very extent of the information that was sought in the questionnaire may have contributed to the relatively small (33%) response rate. However, as stated, it is considered that the information received is sufficiently representative to help planners and providers of CME to ensure that their programs are fulfilling the genuine needs of rural practitioners in South Australia. It is accepted that educational needs are not static; they are always changing due to changing circumstances, changing skill requirements and constantly changing due to changing medical knowledge. The information gained from this survey will require regular updating, and this will be undertaken. PMID- 7880227 TI - Assessment of upper airway anatomy in awake, sedated and anaesthetised patients using magnetic resonance imaging. AB - Magnetic Resonance Imaging was used to quantify the effects of 1. sedation and 2. general anaesthesia with a laryngeal mask airway (LMA) in place on the minimum antero-posterior (A-P) diameters of the naso-, oro- and hypopharynx and on the angle of the epiglottis relative to the adjacent posterior pharyngeal wall. Median sagittal T1-weighted images of the pharynx were obtained in 46 patients (16 awake, 14 sedated, 16 under general anaesthesia). In sedated patients, the A P diameters of the pharynx were less than in awake patients, in particular at the levels of the epiglottis and soft palate. General anaesthesia and placement of a LMA was also associated with a reduced A-P diameter at the level of the soft palate, but with increased diameters at the levels of the tongue and epiglottis. Placement of a LMA caused abnormal downfolding of the epiglottis in most cases but this did not cause clinically significant airway obstruction. PMID- 7880229 TI - Combination products as first-line pharmacotherapy. PMID- 7880228 TI - Oral atovaquone compared with intravenous pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Atovaquone Study Group. AB - OBJECTIVE: To test the hypothesis that the therapeutic success rate of oral atovaquone is not worse than that of intravenous pentamidine in the primary treatment of mild and moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome and to detect differences in the toxicity rates of the two treatments. DESIGN: Patients were randomly assigned to receive 21 days of open-label therapy with either atovaquone, 750 mg orally with meals three times daily, or intravenous pentamidine, 3 to 4 mg per kg body weight once daily. SETTING: Multicenter study including university and community treatment facilities. PATIENTS: Patients with human immunodeficiency virus infection and clinical presentations consistent with mild or moderate P. carinii pneumonia were eligible. For efficacy and safety analyses, patients with histologically confirmed P. carinii pneumonia were emphasized. MEASUREMENTS: Patients were monitored by clinical and laboratory evaluations for therapeutic efficacy and adverse events during the acute treatment phase and for 8 weeks after therapy was discontinued. RESULTS: As initial therapy for a histologically confirmed episode of P. carinii pneumonia, 56 patients received atovaquone and 53 received pentamidine. More patients were successfully treated with atovaquone (57%) than with pentamidine (40%), a difference of 17% (95% CI, -3% to 38%; P = 0.085), but more patients failed to respond to atovaquone (29%) than to pentamidine (17%), a difference of 12% (CI, -6% to 29%; P = 0.18). Discontinuation of original therapy because of treatment-limiting adverse events was more frequent in the pentamidine group (36%) than in the atovaquone group (4%) (difference, -32%; CI, -48% to 17%; P < 0.001). Nine patients in each treatment group died during the study. CONCLUSIONS: Oral atovaquone and intravenous pentamidine have similar rates for successful treatment of mild and moderate P. carinii pneumonia, but atovaquone has significantly fewer treatment-limiting adverse events. PMID- 7880230 TI - Handicap one year after a stroke: validity of a new scale. AB - The aim was to determine the handicap experienced by subjects one year after a stroke, and assess the acceptability, validity, and reliability of a new handicap measurement scale. A cross sectional survey of 141 survivors of a cohort of consecutive hospital admissions with acute stroke was undertaken. The London handicap scale (a new health outcome measurement scale), Barthel index, Nottingham extended activities of daily living scale, Nottingham health profile, Geriatric depression score, and a global life satisfaction scale were used. 94 subjects (67%) responded to a single mailing; 89 (95%) responses were usable. Mean handicap was 0.40 (range 0.06-1.0, SD 0.20) on a scale of 0 (maximum handicap) to 1 (no handicap). All handicap dimensions showed a wide range of problems, with physical independence and occupation particularly affected. Correlations between handicap score and other outcome measures were all in the expected direction and of about the strength expected (0.36 < r < 0.69). The reliability coefficient was 0.91, limits of agreement +/- 0.19. The measurements demonstrated substantial handicap one year after a stroke, reflecting considerable unmet rehabilitation needs. The scale proved acceptable to subjects, and the results were consistent with good validity. PMID- 7880231 TI - Risk, risk assessment, and risk labels. PMID- 7880232 TI - Neurosyphilis and HIV infection. PMID- 7880233 TI - The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. AB - BACKGROUND: The pathogenesis of unstable angina is poorly understood, and predicting the prognosis at the time of hospital admission is problematic. Recent evidence suggests that there may be active inflammation, possibly in the coronary arteries, in this syndrome. We therefore studied the prognostic value of measurements of the circulating acute-phase reactants C-reactive protein and serum amyloid A protein, which are sensitive indicators of inflammation. METHODS: We measured C-reactive protein, serum amyloid A protein, creatine kinase, and cardiac troponin T in 32 patients with chronic stable angina, 31 patients with severe unstable angina, and 29 patients with acute myocardial infarction. RESULTS: At the time of hospital admission, creatine kinase and cardiac troponin T levels were normal in all the patients, but the levels of C-reactive protein and serum amyloid A protein were > or = 0.3 mg per deciliter (exceeding the 90th percentile of the normal distribution) in 4 of the patients with stable angina (13 percent), 20 of the patients with unstable angina (65 percent), and 22 of the patients with acute myocardial infarction (76 percent). The 20 patients with unstable angina who had levels of C-reactive protein and serum amyloid A protein > or = 0.3 mg per deciliter had more ischemic episodes in the hospital than those with levels < 0.3 mg per deciliter (mean [+/- SD] number of episodes per patient, 4.8 +/- 2.5 vs. 1.8 +/- 2.4; P = 0.004); 5 patients subsequently had a myocardial infarction, 2 died, and 12 required immediate coronary revascularization. In contrast, no deaths or myocardial infarction occurred among the 11 patients with levels of C-reactive protein and serum amyloid A protein < 0.3 mg per deciliter, and only 2 of them required coronary revascularization. Among the patients admitted with a diagnosis of acute myocardial infarction, unstable angina preceded infarction in 14 of the 22 patients (64 percent) with levels of C reactive protein and serum amyloid A protein > or = 0.3 mg per deciliter but in none of the 7 patients with levels < 0.3 mg per deciliter. CONCLUSIONS: Elevation of the sensitive acute-phase proteins C-reactive protein and serum amyloid A protein at the time of hospital admission predicts a poor outcome in patients with unstable angina and may reflect an important inflammatory component in the pathogenesis of this condition. PMID- 7880234 TI - Insurance-related differences in the risk of ruptured appendix. AB - BACKGROUND: We studied differences in the incidence of appendiceal perforation in patients with acute appendicitis according to their insurance coverage. METHODS: In a retrospective analysis of hospital-discharge data, we examined the likelihood of ruptured appendix among adults 18 to 64 years old who were hospitalized for acute appendicitis in California from 1984 to 1989. RESULTS: After controlling for age, sex, psychiatric diagnoses, substance abuse, diabetes, poverty, race or ethnic group, and hospital characteristics, we found that ruptured appendix was more likely among both Medicaid-covered and uninsured patients with appendicitis than among patients with private capitated coverage (odds ratios, 1.49 [95 percent confidence interval, 1.41 to 1.59] and 1.46 [95 percent confidence interval, 1.39 to 1.54], respectively). After adjustment for the above factors, the risk of appendiceal rupture associated with a lack of private insurance was elevated at both county and other hospitals, but admission to a county hospital was an independent risk factor. In all income groups, appendiceal rupture was more likely with fee-for-service than capitated private coverage (overall odds ratio, 1.20 [95 percent confidence interval, 1.15 to 1.25]). CONCLUSIONS: Among patients with appendicitis an increased risk of ruptured appendix may be due to insurance-related delays in obtaining medical care. Both organizational and financial features of Medicaid and various types or levels of private third-party coverage may be involved. The significant association between ruptured appendix and insurance coverage after adjustment for socio-economic differences suggests barriers to receiving medically necessary acute care that should be considered in current deliberations on health policy. PMID- 7880235 TI - Turbulent times for emergency medicine: health care reform, board certification, contract management, and the growth of new organizations in emergency medicine. PMID- 7880236 TI - Adverse interaction between warfarin and indomethacin. AB - A 57-year-old man developed spontaneous skin bruising and haematuria during combined therapy with warfarin and indomethacin. Due to the potential effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the anticoagulant action of warfarin and platelet function, patients receiving both warfarin and NSAIDs should have their prothrombin time monitored very closely. Also, the risk of gastrointestinal haemorrhage with any NSAIDs must always be remembered. PMID- 7880237 TI - Something rotten in the state of clinical and economic evaluations? PMID- 7880238 TI - Enterocutaneous fistulae in horses: 18 cases (1964 to 1992). AB - Enterocutaneous fistulae are rare in horses and occur most commonly as a complication of umbilical hernias or their treatment. Horses with enterocutaneous fistulae may be successfully treated by en bloc resection of the body wall and intestine or by allowing second intention healing. Complications associated with surgical intervention include fever, colic, incisional problems, and recurrence of the fistula. Nonsurgical management of two horses with presumptive large colon fistulae resulted in resolution of the fistulae without complications. PMID- 7880239 TI - Complexity of the healthcare crisis in rural America. AB - Because osteopathic physicians comprise 15.3% of all physicians in small rural counties, while making up only 5.1% of the nation's physicians, the solutions to the healthcare crisis for rural America are of special interest to them. The authors explore the incredible diversity of rural communities and the difficulty with defining the term "rural." They give the background of efforts to address rural health problems and the reasons accessible healthcare--available, acceptable and affordable--has been so elusive in rural settings. The authors also explain the relative success of the osteopathic medical profession and address the role osteopathic physicians can play in the future. Finally, they explore the exciting new possibilities that telemedicine offers. PMID- 7880240 TI - Management of cancer of the prostate. PMID- 7880241 TI - Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe. AB - In a study of the pathogenesis and clinical features of megaloblastic anaemia in southern Africa, we evaluated 144 consecutive Zimbabwean patients with megaloblastic haemopoiesis. Vitamin B12 deficiency was diagnosed in 86.1% of patients and was usually due to pernicious anaemia; isolated folate deficiency accounted for only 5.5% of cases. Anaemia was present in 95.8% of patients; the haemoglobin (Hb) was < or = 6 g/dl in 63.9%. Neurological dysfunction was noted in 70.2% of vitamin B12-deficient patients and was most striking in those with Hb values > 6 g/dl. Serum levels of methylmalonic acid, homocysteine, or both, were increased in 98.5% of patients. Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe and, contrary to textbook statements, is often due to pernicious anaemia. Isolated folate deficiency is less common. As reported in industrialized countries 75 years ago, anaemia is almost always present and often severe. Neurological dysfunction due to vitamin B12 deficiency is most prominent in patients with mild to moderate anaemia. PMID- 7880242 TI - Pelvic inflammatory disease in the adolescent. AB - This article reviews new developments in the detection and treatment of pelvic inflammatory disease, including known risk factors, microbial etiologies, treatment standards, and associated morbidity. The use of transvaginal ultrasound and the role of the male partner in infection control is also discussed. PMID- 7880243 TI - Normal transcutaneous oxygen pressure in skin after radiation therapy for cancer. AB - BACKGROUND: Chronic deleterious changes in human skin after radiation therapy often have been ascribed to progressive ischemia (decreased blood supply and oxygenation). Recent studies suggest, however, that damaged irradiated skin is not ischemic. Transcutaneous oxygen pressure (TCPO2), that accurately reflects skin oxygenation, was studied in 100 patients who had undergone prior extensive radiation therapy for cancer. METHODS: In the 100 patients, the mean time since radiation was 7.86 +/- 10.56 years (mean, +/- SD) (range, 1-58 years). Radiation skin effects were graded (0-4+), and TCPO2 was measured in irradiated and control nonirradiated sites, with patients first breathing room air, then 100% O2 6 l/min for 10 minutes. Data were stratified according to skin grades, sex, time since irradiation, site, type, and dose of radiation. RESULTS: The mean TCPO2 in patients breathing room air was 52.0 17.8 mm Hg (mean +/- SD) for all irradiated skin, compared with 131.8 +/- 51.1 at the same irradiated sites in response to oxygen breathing (P < 0.0001); the mean TCPO2 for normal, nonirradiated skin was 56.5 +/- 12.6 when patients were breathing room air, compared with 151.5 +/- 48.1 when breathing 100% oxygen (P < 0.0001). Higher skin damage grades correlated with increasing time after radiation therapy. However, neither increasing time after irradiation nor grade of skin damage correlated with TCPO2, which was normal in 88% of the patients. CONCLUSIONS: Human skin, even many decades after radiation therapy, retains normal tissue oxygenation and TCPO2 response to inspired oxygen. Postradiation scarring, poor healing, and rare ulceration are not solely due to ischemia and may be caused by other radiation effects, such as permanent changes in fibroblasts. PMID- 7880244 TI - Headache and a normal angiogram. PMID- 7880245 TI - Forensic DNA typing dispute. PMID- 7880246 TI - Protection of cattle against rinderpest and lumpy skin disease with a recombinant capripoxvirus expressing the fusion protein gene of rinderpest virus. AB - Cattle were protected against challenge with rinderpest and lumpy skin disease viruses by vaccination with a recombinant capripoxvirus containing the fusion protein (F) gene of rinderpest virus. The minimum protective immunising doses for rinderpest and lumpy skin disease were 5.5 x 10(4) plaque forming units (pfu) and 1.5 x 10(3) pfu, respectively. PMID- 7880247 TI - The effect of age at smoking initiation on lung cancer risk. PMID- 7880248 TI - Nursing malpractice litigation: a personal journey. PMID- 7880249 TI - Actigraphy and insomnia: a closer look. Part 1. AB - In recent years, wrist actigraphy has been scrutinized as a possible supplement to or even replacement for other methods traditionally used to assess the sleep of clinical patients and research subjects. While showing promise for some applications, its accuracy in measuring the nocturnal sleep of insomniacs remains in question. A reexamination of the relevant data indicates that with respect to estimating the total sleep time of insomnia patients, use of the actigraph does not yield significantly lower error than daily sleep logs and predicts only about a third of the variance. However, the actigraph does show some potential for assessing the night-to-night variability of a given individual's sleep, suggesting that it may be most useful for assessing longitudinal changes within a treatment program or experimental protocol. PMID- 7880250 TI - Primary care. PMID- 7880251 TI - Characterization of the coenzyme-B12-dependent glutamate mutase from Clostridium cochlearium produced in Escherichia coli. AB - The glutamate mutase dependent on adenosylcobalamin (coenzyme B12) catalyzes the carbon skeleton rearrangement of (S)-glutamate to (2S,3S)-3-methylaspartate, the first step of the glutamate fermentation pathway of the anaerobic bacterium Clostridium cochlearium. The enzyme consists of two protein components, E, a dimer epsilon 2 (epsilon, 53.5 kDa) and S, a monomer (sigma, 14.8 kDa). The corresponding genes (glmE and glmS) were cloned, sequenced and over-expressed in Escherichia coli. The genes glmS and glmE are separated by glmL encoding a protein of unknown function. The deduced amino acid sequence of GlmL contains an ATP-binding motif which is common to chaperones of the HSP70-type, actin and procaryotic cell-cycle proteins. Both components of glutamate mutase were purified with excellent yields from cell-free extracts of E. coli carrying the corresponding genes. In contrast to component E, component S was shown to bind coenzyme B12. This observation strongly supports the idea that significant similarities of the amino acid sequences of component S and several other cobamide-dependent enzymes represent a common binding motif. Incubation of pure components E and S with coenzyme B12 resulted in the formation of a fully active glutamate mutase heterotetramer (epsilon 2 sigma 2) containing one molecule of coenzyme B12. EPR spectra of recombinant glutamate mutase, now available in sufficiency large amounts, were recorded after incubation of the enzyme with coenzyme B12 and (S)-glutamate. The EPR signals (gx,y approximately 2.1, gz = 1.985) were of much better resolution than observed earlier with the clostridial enzyme. Their typical hyperfine splitting is clearly derived from Co(II), which is involved in the formation of the paramagnetic species but is different from cob(II)alamin (gx,y = 2.25). The spin concentration was 34-50% of the concentration of the enzyme (epsilon 2 sigma 2) coenzyme complex. The competitive inhibitors (2S, 4S)-4-fluoroglutamate and 2-methyleneglutarate induced similar but not identical signals with spin concentrations of 134-148% of the enzyme concentration. Even (S)-[2,3,3,4,4-2H5]glutamate induced a signal significantly different to that of (S)-glutamate with an intensity of only 7%. These data suggest an involvement of the Co(II)-containing paramagnetic species in catalysis, the concentration of which reflects a steady state between its formation and decomposition. The large difference in the spin concentrations observed with (S)-glutamate as compared to the predeuterated glutamate is probably due to a kinetic isotope effect and indicates a cleavage of a C-H bond during formation of the paramagnetic species.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7880252 TI - Proposed guidelines for American Dental Association acceptance of products for professional, non-surgical treatment of adult periodontitis. Task Force on Design and Analysis in Dental and Oral Research. AB - Guidelines are suggested for determining efficacy of products to supplement scaling and root planing in professional, non-surgical treatment of adult periodontitis. They result from an extended process including a conference on clinical trials in gingivitis and periodontitis, a subsequent workshop, and commentary from industrial, academic, professional and governmental members of the periodontal research community on two drafts. Recommendations are made in the broad areas of basic study design, subject and periodontal site selection, clinical management, choice of outcome variables, statistical summarization and analysis, and criteria for acceptance. Prominent dissenting views, with justifications for positions taken here, are also provided. Groundwork is laid for possible future guidelines addressing products for primary prevention or over the-counter uses, or for determining superiority or equivalence of competing products. However, issues are identified which require further exploration before responsible and widely acceptable recommendations can be made in these areas. The guidelines suggested here are meant to form the basis of an evolving document rather than a static standard. It is suggested that they be reviewed frequently in the light of improvement in the technology available for periodontal research, and the emergence of products representing new approaches to periodontal therapy. PMID- 7880253 TI - The difficulty in predicting behavior of smooth-muscle tumors in deep soft tissue. PMID- 7880254 TI - Standards for interhospital transfer. PMID- 7880255 TI - Acute paraplegia following intrathecal phenol block. PMID- 7880256 TI - Combination products as first-line pharmacotherapy. PMID- 7880257 TI - Brachial plexus injury. PMID- 7880258 TI - Mothers of molested children: some comparisons of personality characteristics. PMID- 7880259 TI - Using the nicotine patch to stop smoking. PMID- 7880260 TI - Individualized treatment of alcohol withdrawal. PMID- 7880261 TI - Support for the emergency nurse practitioner role. PMID- 7880262 TI - Mammary ducts in the areola: implications for patients undergoing reconstructive surgery of the breast. PMID- 7880263 TI - "The Duesberg phenomenon": what does it mean? PMID- 7880264 TI - Single tooth replacement--expanded treatment options. PMID- 7880265 TI - Animal testing in research is not always necessary. PMID- 7880266 TI - Use of pentoxifylline in the treatment of cerebral malaria. PMID- 7880267 TI - Circadian rhythmic variations in serum concentrations of clinically important lipids. PMID- 7880268 TI - Medical personnel's knowledge of the ability to use inhaling devices. PMID- 7880269 TI - Clinical usefulness of clozapine. PMID- 7880270 TI - Aeromonas caviae exhibits aggregative adherence to HEp-2 cells. PMID- 7880271 TI - Postoperative angiography. PMID- 7880272 TI - Occult malformation with anomalous venous drainage. PMID- 7880273 TI - Familial Pallister-Hall syndrome. PMID- 7880274 TI - Surgical glove perforation during cardiac operations. PMID- 7880275 TI - Acinetobacter infections, intensive care units, and handwashing. PMID- 7880276 TI - Acinetobacter infections, intensive care units, and handwashing. PMID- 7880277 TI - Chronic fatigue syndrome. PMID- 7880278 TI - Factor V Leiden mutation and venous thrombosis. PMID- 7880279 TI - Article on Detroit-Macomb Hospital Center bylaws dispute draws fire. A puddle of prevarications. PMID- 7880280 TI - Management of cancer of the prostate. PMID- 7880281 TI - More on DNA typing dispute. PMID- 7880282 TI - More on DNA typing dispute. PMID- 7880283 TI - Three-phase bone scans and neonatal osteomyelitis. PMID- 7880284 TI - Men in nursing. PMID- 7880285 TI - Photosensitivity-induced retinal atrophy in albino rat. PMID- 7880286 TI - Evaluation of barrier creams: an in vitro technique on human skin. PMID- 7880287 TI - Competent valves! Competent editing? PMID- 7880288 TI - Autotransfusion of shed mediastinal blood after cardiac operations. PMID- 7880289 TI - Videothoracoscopy and spontaneous pneumothorax. PMID- 7880290 TI - Neurosyphilis and HIV infection. PMID- 7880291 TI - Medicine's core values. Both knowledge and compassion are needed. PMID- 7880292 TI - Medicine's core values. Are based on Christian ethics. PMID- 7880293 TI - The future of public health. Forget the old days of medical officers of health. PMID- 7880294 TI - 'Cough sign': a reliable test in the diagnosis of intra-abdominal inflammation. PMID- 7880295 TI - Table for II. PMID- 7880296 TI - Validity of the London handicap scale. PMID- 7880297 TI - Fetal biometry of skeletal dysplasias: a multicentric study. AB - Twenty-three diagnostic centers worldwide contributed 127 cases of 17 skeletal dysplasias. Discriminant analysis showed that the femur length was the best biometric parameter to distinguish among the five most common disorders in this series (thanatophoric dysplasia, osteogenesis imperfecta type II, achondrogenesis, achondroplasia and hypochondroplasia). Fifty-four percent of fetuses with femur length below 30% of the mean for gestational age had achondrogenesis. Seventy-eight percent of measurements between 40 and 60% of the mean for gestational age represented either thanatophoric dysplasia or osteogenesis imperfecta type II. Fetuses who had over 80% of the mean for gestational age had predominantly hypochondroplasia, achondroplasia, and osteogenesis imperfecta type III. PMID- 7880298 TI - Apolipoprotein E E4 allele and risk of dementia. PMID- 7880299 TI - Congenital bilateral absence of vas deferens in absence of cystic fibrosis. PMID- 7880300 TI - Giving credit where it's due: chocolate chip cookies. PMID- 7880301 TI - Insurance and the risk of ruptured appendix. PMID- 7880302 TI - Quality of life after myocardial infarction: Canada versus the United States. PMID- 7880303 TI - Knowledge of drugs for myocardial infarction: generalists versus specialists. PMID- 7880304 TI - Antibodies to botulinum toxin. PMID- 7880305 TI - "The Duesberg phenomenon": Duesberg and other voices. PMID- 7880307 TI - Occupational therapists have experience in job analysis and pain management. PMID- 7880306 TI - Possible association between monoamine oxidase A gene and bipolar affective disorder. PMID- 7880308 TI - Absence of human papillomavirus in squamous cell carcinomas of nongenital skin from immunocompromised renal transplant patients: a comment. PMID- 7880309 TI - Use of the hydroxyapatite ocular implant in the pediatric population. PMID- 7880310 TI - Oral megadose methylprednisolone for the treatment of Diamond-Blackfan anemia. PMID- 7880311 TI - Beware of oatmeal. PMID- 7880312 TI - Perception or agenda. PMID- 7880313 TI - Influence on recombinant human erythropoietin on hemorheological profiles of hemodialyzed patients. PMID- 7880314 TI - Community-acquired Acinetobacter pneumonia. PMID- 7880315 TI - On turbulent times for emergency medicine. PMID- 7880316 TI - Management of tetanus. PMID- 7880317 TI - More on acute surgical conditions. PMID- 7880318 TI - Review article: mechanisms of ion transfer by the rat placenta: a model for the human placenta? PMID- 7880319 TI - Short-term course of renal function in accelerated hypertension. AB - Thirty-four patients with primary accelerated hypertension were studied regarding the effect of BP on renal function and the association between fundal grade and renal function before treatment; and the changes in renal function on normalization of BP in 12 patients. Mean arterial pressure was negatively correlated with serum creatinine (r = -0.44, P < 0.02) and there was no significant difference in serum creatinine or in the occurrence of renal failure between patients with grade III (n = 21) and grade IV (n = 13) retinopathy, (P = n.s. and X2 = 0.172 P = n.s. respectively). Twenty-two patients required dialysis at presentation. Serum creatinine rose in 12 other patients on reduction of BP; 7 patients with serum creatinine level < or = 3.2 mg/dL (283 umol/L) at presentation never required dialysis in the 3 months following reduction of BP while those with levels > or = 3.6 mg/dL (319 umol/L) did. In accelerated hypertension, renal function is partly maintained by the blood pressure and dialysis may be required soon after presentation or normalization of BP. PMID- 7880320 TI - Genomic organization of the Btk gene and exon scanning for mutations in patients with X-linked agammaglobulinemia. AB - The defective gene responsible for the recessively inherited immunodeficiency X linked agammaglobulinemia (XLA) has been shown to encode a cytoplasmic protein tyrosine kinase of the Src family designated Btk (Bruton's tyrosine kinase). To facilitate the search for germline mutations of the Btk gene, we have characterized its genomic structure. Eighteen introns were positioned within the approximately 37 kb gene. Each of the exon/intron boundaries were defined and sequenced, and all but two conform to consensus sequences. We have utilized the genomic organization of Btk and the intervening sequence data to design an assay for amplifying each of the 19 exons from XLA patient DNA for single strand conformation polymorphism (SSCP) analysis. By using this method we have identified mutations in 12 of 14 unrelated affected males: seven different base substitutions and two small deletions. Two of the mutations described in exon 15 of the kinase domain were found in more than one patient and may represent a mutation hot spot. Exon scanning has proven to be a valuable method for identifying the patient mutations in genomic DNA without the use of cDNA. The mutations are easily confirmed with direct sequencing of the amplified exons. This approach will greatly benefit XLA family studies involving carrier detection and prenatal diagnosis. In addition, the mutations identified may reveal residues involved in the specific protein interactions necessary in the B-cell developmental pathway, of which Btk is an integral component. PMID- 7880321 TI - Cytochrome P450 changes in rats with streptozocin-induced diabetes. AB - It is known that the metabolism of some drugs is altered in diabetic patients and in rats with experimental diabetes induced by chemical agents, such as streptozocin. The induction and/or suppression of hepatic cytochrome P450 isozymes seen in diabetes seem to contribute to this alteration. Both metabolic and hormonal disturbances following insulin deficiency in diabetic rats are responsible for these changes. Marked changes in hepatic P450 isozymes in diabetic rats include increases in the isozymes induced by ketones and lipids, including fatty acids, and decreases in the isozymes regulated by growth hormone and testosterone. Suppressed secretion of thyroid hormones also participates in the mechanism causing these changes. Analysis of cytochrome P450 isozymes in diabetic rats is helpful in elucidating the impaired metabolism of some endogenous substrates catalyzed by the cytochrome P450, such as steroid hormones and fatty acids, in diabetes. The results of these analyses also provide insight into the prescription of drugs for diabetic patients. PMID- 7880322 TI - Dietary salt intake and blood pressure among schoolchildren. AB - We studied the relationship between dietary salt intake, urinary salt excretion, blood pressure and anthropometric measurements in 322 Japanese schoolchildren, aged between 6 and 11 years. Two surveys were carried out: one among a small group of 22 children from the 322, and one involving all 322. In the former group, both a detailed and a simplified dietary questionnaire were used, and nocturnal and 24 hr urinary salt excretion samples were collected. The latter group's survey used only the simplified questionnaire and nocturnal salt excretion measurements. The surveys from the two different groups were then compared to each other. It was found that the simplified questionnaire and nocturnal urinary samples were statistically accurate enough to be used for the purpose of this study. From the latter survey, dietary salt intake among the children was 7.5 +/- 2.7 g per day, (mean +/- SD), and 65 pupils (20%) consumed more than 10 g of salt per day. It was also found that nocturnal urinary salt excretion levels were 1.47 +/- 0.82 g per day, with 30 pupils (9.3%) registering levels of more than 2.5 g per day. There was a significant correlation between these dietary and urinary salt levels. Systolic blood pressure (SPB) among the schoolchildren showed significant correlation with age, height, weight and BMI. For diastolic blood pressure (DBP), a significant correlation was seen in age only. SBP and DBP showed little relation with either dietary salt intake or urinary salt excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880323 TI - [Thermal insulation of clothing for seated and standing postures]. AB - The purpose of this study is to examine the effects of body posture on thermal insulation of clothing. Clothing ensembles including skirts were mainly investigated. A new thermal manikin was developed for this study. This manikin was able to change her body posture without increasing or decreasing her surface area. By changing posture from standing to seated, the total thermal insulation of clothing (It) was decreased by around 1.4%. The surface thermal resistance at nude (Ia) was increased by 8%. As a result, the basic thermal insulation of clothing (Icl) was decreased by 14%. The main reason for the decrease of basic thermal insulation (Icl) when the posture of thermal manikin changes from standing to seated was the increase of Ia at nude. The total thermal insulation of clothing for each body posture (Iti), when standing and seated, were compared. The parts affected by the changed posture were abdomen, hip and thighs, and especially under the skirt of 61cm length, the knees were most affected. PMID- 7880324 TI - [Influence of physical responses due to controlled frequency breathing during exercise]. AB - The purpose of this study was to examine the influence of respiratory responses due to controlled frequency breathing (CFB) during steady state cycle ergometric exercise (50% of Peak VO2, 60rpm) and to compare their responses between long distance (L), badminton (B), Swimming (S) and untrained (C; Control) group. Twenty-two (n = 6; L, B, C.n = 4; S) female university students were forced to take CFB for 1 min every 3 min during 20 min exercise. The breathing frequencies (BR) were 10, 12, 15, 20 and 30 frequencies in a minute. They were represented by CFB10, CFB12, CFB15, CFB20 and CFB30 respectively. In addition, CFB5, and 40 were given in a separate series. Ventiratory volume (VE) decreased significantly, (P < 0.05) when BR decreased less than about 50% of normal breathing (NB), CFB15 in (B) and (C). It showed to be less than CFB12 in (S), and CFB10 in (L). According to the decrease of VE, tidal volume and O2 pulse increased during CFB10 and 15 in all groups to maintain a constant O2 consumption for a given workload. End tidal partial pressure of O2 (PETO2) significantly decreased during less than CFB15 in (B) and (C), during CFB10 in (L). PETCO2 increased during less than CFB15 in (B), less than CFB12 in (L) and (C). However in (S) during every CFB, neither PETO2 nor PETCO2 changed significantly. Talking about the main differences shown between the four groups, (S) and (L) significantly exceeded (C) in maintaining of VE during CFB. However, in consideration of a ratio of the frequency of CFB to that of NB, (L) could maintain VE against more strictly controlled of breathing than other groups. (B) showed similar tendencies as (C) about some responses. It is considered that these differences in respiratory responses to CFB may result from difference of the duration and the level of breathing control that were forced during their daily training rather than whether their breathing frequency during each exercise is high or low. PMID- 7880325 TI - [Comparison of formulas for calculating average skin temperature and their characteristics]. AB - In order to obtain data of skin temperatures experiments were carried out using three healthy young Japanese males. The subjects were exposed to each of the four environments with dry bulb temperatures of 15 degrees C, 19 degrees C, 25 degrees C and 33 degrees C. At each of these air temperatures, relative humidity and air movement were set at 50% and 0.15m/s respectively. The subjects wore only athletic shorts, seated on the meshed chair. Each subject was measured with thermisters continuously for one hour under these conditions to obtain twenty nine regional skin temperature. The above experiments were made with one subject at a time in the test chamber. The data of skin temperatures observed were substituted into twenty-eight different weighting formulas for comparison. The present analysis revealed that the calculation from the 12-point and the 7-point skin area formulas by Hardy-DuBois showed approximate mean values of the twenty eight. Moreover, the values calculated from the formula by Nadel et al, which was weighted by skin area and thermal sensitivity, are similar to the values calculated by the formula of Mochida, which was weighted by skin area, heat transfer coefficients and thermal sensitivity. Furthermore, the authors verified that the area-mean weighting factor was derived from the Teichner's definition in which a limiting value of arithmetical mean of skin temperatures gave a value of average skin temperature. PMID- 7880326 TI - [The regional skin temperature of hand under different clothing conditions]. AB - The change in the regional skin temperature of hand was investigated under two different clothing conditions. The skin temperatures at six points on the palm, dorsum, and middle finger of the hand, respectively, were measured by using thermister thermometers simultaneously. The measurements were performed in a climate chamber conditioned at 20 degrees C and 65% R.H.. The subjects were 10 healthy females aged between 20 and 24 years. Five out of the 10 subjects wore light clothing (ca. 0.36 clo) and the others heavy clothing (ca. 0.75 clo). They first rested sitting on a chair for 30 min in the climate chamber before the onset of measurement. The results are as follows: 1) The skin temperature of the palm was higher than that of the other parts. Data were rather scattered in the case of the middle finger. 2) The skin temperature of the middle finger dropped to about 3 degrees C within 20 min after the start of measurement. 3) The skin temperature of the middle finger was affected by the clothing condition. We imagine that the skin temperature of the middle finger closely relates to arteriovenous anastomoses (AVA) located in the finger. Clothing probably plays an important role in controlling the blood flow of the AVA vessels, and consequently the skin temperature of the middle finger changes more sensitively than other parts of the hand. PMID- 7880327 TI - Classification of body shape of male athletes by factor analysis. AB - The purpose of this study was to evaluate the body shape of athletes in comparison with adult non-athletes by factor analysis. The subjects were 210 male adult non-athletes and 485 male high school age and adult athletes participating in 13 different sporting events. Physique, skinfold thickness and body composition of each subject were measured. Measured values from adult non athletes were analyzed by factor analysis, and body shape of the athletes was then analyzed according to these factors. The results are summarized as follows: 1. Four main factors, that is, body fat, mass, leg length to height ratio and length, which could explain 88.5 percent of total variance, were extracted from the measured values from adult non-athletes. 2. Similarity of body shape between sporting events was analyzed by cluster analysis. Body shape of the athletes could be classified into 3 categories: muscular and well-balanced type; rich muscular and large-built type; and rich muscular and long-torso type. Compared with adult non-athletes, male athletes had less body fat and greater mass except for long-distance runners. The present results suggested that the athletes had body shapes suitable to their sporting events. PMID- 7880328 TI - [Protein metabolism in vegans]. AB - To elucidate the mechanisms of adaptation to a low-energy and low-protein vegan diet, we carried out dietary surveys and nitrogen balance studies five times during one year on two women and a man who ate raw brown rice, raw green vegetables, three kinds of raw roots, fruit and salt daily. Individual subjects modified this vegan diet slightly. The mean daily energy intake of the subjects was 18, 14, and 32 kcal/kg, of body weight. The loss of body weight was about 10% of the initial level. The daily nitrogen balance was -32, -33, and -11 mg N/kg of body weight. In spite of the negative nitrogen balance, the results of routine clinical tests, initially normal, did not change with the vegan diet. Ten months after the start of the vegan diet, the subjects were given 15N urea orally. The incorporation of 15N into serum proteins suggested that these subjects could utilize urea nitrogen for body protein synthesis. The level of 15N in serum proteins was close to the level in other normal adult men on a low-protein diet with adequate energy for 2 weeks. PMID- 7880329 TI - [Evaluation of physical exercise and fatigue sensation by CFSI (Cumulative Fatigue Symptoms Index)]. AB - Cumulative Fatigue Symptoms Index (CFSI) is used for workers' subjective assessment of feeling of fatigue and of symptoms. Until now, this index has been used in the analysis of members of the same occupation. The purpose of this study is to examine fatigue symptoms in workers and to assess by CFSI the effect of regular physical exercise. Study participants were an exercise group (n = 67) and a non-exercise group (n = 115) of older workers, aged from 30 to 69 years. The CFSI questionnaire was distributed to all participants and the former group (exercise) answered two descriptive questions concerning the aim and subjective effects of physical exercise. As a result, it was found that mental fatigue symptoms decreased in the exercise group even after considering the differences in managerial position, subjective senses on health and marital status which are related to degree of feelings of fatigue. Weakened vitality was significantly less in the exercise group than the non-exercise group. Therefore, we concluded that weakened vitality would be needed to be regarded on an assessment scale for effects caused by exercise. It has also been considered that we should investigate general fatigue in assessing physical fatigue relating to one's lifestyle. PMID- 7880330 TI - [Saturation diving system at high altitude]. AB - Practical saturation diving was firstly performed at high altitude in Japan in 1987. Its work was to change the screen which had covered the pipeline of a hydroelectric dam located 850 meters above sea level, the same operation had been conducted in 1992 and in 1993, 2 times each year (Total = 5 operations) after the work. The saturation dives have lasted from six to eight days on 4 occasions and 13 days (Total duration = 4075 minutes) on 1 occasion, since the initial pressurization until the end of the last decompression. In each operation, there had always been involved 3 divers. They have been compressed to an equivalent depth of 45-73m in the deck decompression chamber (DDC), briefed for work and transferred to the submersible decompression chamber (SDC), which was then submersed to 53-78m of depth. Wearing heated suit and breathing Heliox (both at the same temperature as the inside of the SDC), the divers have been locked out to perform their tasks, all monitored and supervised by the use of a remotely operated vehicle (ROV). The works have run uneventful and successfully until the end. The water temperature had been higher than the expected, i.e. 9-13 degrees C in all occasions. The inside conditions of the chamber had been the following: partial pressure of nitrogen was from 0.78 ATA; partial pressure of oxygen was from 0.35 to 0.40 ATA; partial pressure of carbon dioxide was less than 0.005 ATA; the inside temperature of the SDC was from 26 to 30 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880331 TI - [The effects of environmental thermal condition on transitional skin temperature of peripheral parts of human hands and feet during exercise]. AB - The effects of environmental temperature on transitional skin temperatures of peripheral parts of human hands and feet were examined during exercise to obtain basic information on thermal characteristics of heat transfer from human body to the environment. Very thin and fat male adults served as subjects who were in contrast regarding fat content. Their skin temperatures were undertaken by thermocouples in a climate chamber. The exercise was made using an ergometer at three stages of the chamber temperatures. The skin temperature of a fat subject's trunk was observed to be lower than that of thin subject due to the insulation of fat in the body. In compensation for less heat transfer from the trunk, the temperatures of peripheral parts of fat subject's hands and feet were higher than that of the thin subject. Moreover, the response of the temperature to the thermal load due to exercise was observed to be quicker. These kinds of variation were considered as due to the increase in blood flow through arteriovenous anastomoses, AVA. It seemed that AVA blood of the thin subject did not increase during resting condition at the environmental temperatures of 10 and 20 degrees C but was accelerated by the thermal load due to exercise. In addition, the response of AVA on the foot seemed to be delayed compared with that on the hand. PMID- 7880332 TI - Neonatal encephalopathies as classified by EEG-sleep criteria: severity and timing based on clinical/pathologic correlations. AB - Neonatal encephalopathies can be characterized in functional terms using electroencephalography. Severity of an encephalopathic state can also be estimated by electrographic interpretation independent of the time of disease process onset. Moderately or markedly abnormal electroencephalographic patterns on serial studies are highly correlated with neurologic sequelae in survivors. Electroencephalography is rarely pathognomonic or specific in determining when a condition initially occurred. However, electroencephalographic abnormalities are associated with different clinical situations, and brain lesions documented on neuroimaging or with postmortem neuropathologic examination are observed in infants with certain abnormal electrographic patterns. When interpreted in the context of history, clinical findings, and other laboratory information, the neurophysiologic studies augment the understanding of both the severity and timing of an encephalopathic state. PMID- 7880333 TI - Technetium-99m HmPAO brain SPECT and outcome of hemispherectomy for intractable seizures. AB - With recent descriptions of the modified hemispherectomies and hemicorticectomy, there has been renewed interest in hemispherectomy for treatment of intractable seizures with hemiparesis. Because long-term outcome remains uncertain, patient selection remains difficult. 99mTc-HmPAO brain SPECT has been a helpful adjunct in the evaluation of epilepsy surgery candidates. We report SPECT scan findings in 7 patients who underwent hemispherectomy and compare these results with scalp EEG findings. Six patients had unilateral SPECT findings and all had a favorable outcome, regardless of surface EEG findings. PMID- 7880334 TI - Presentation, clinical course, and outcome of the congenital form of myotonic dystrophy. AB - We report the clinical experience of 18 patients with the congenital form of myotonic dystrophy, the majority of whom were diagnosed during the neonatal period and monitored from 5 to 14 years. Prematurity associated with congenital myotonic dystrophy gives rise to the severest clinical manifestations. Among them, respiratory involvement is common and is the leading cause of death in the neonatal period. Weakness and foot deformities secondary to muscle involvement are the predominant clinical features of this group of patients from birth to age 3 or 4 years. Once muscle strength improves, learning disabilities and behavioral disturbances become the main clinical problems. All our patients, when tested after 5 years of age, had intelligence quotients under 65, clearly below the average intelligence quotient of their mothers (IQ = 80). There is no relationship between the degree of mothers' and patients' disease. No patient has presented problems with routine immunizations, and no complications were observed in the 7 patients who underwent surgery under general anesthesia. Among the surviving patients, no correlation can be established between severity of disease in the neonatal period and the magnitude of sequelae as teenagers. Mental and behavioral disturbances are the factors which mainly influence the long-term management and prognosis of this cohort of individuals. PMID- 7880335 TI - Comparative estimates of neonatal gestational maturity by electrographic and fetal ultrasonographic criteria. AB - We previously reported a high correlation between electrographic and postmortem neuroanatomic (i.e., sulcal-gyral) estimates of maturity in sick preterm neonates who were clinically abnormal because of neonatal medical illnesses. Electroencephalographic studies have not yet been compared with ultrasonographic measurements in healthy fetuses who subsequently had normal neurodevelopmental outcome. Twenty-five EEG recordings on healthy neonates (28-43 weeks postconceptional age) had EEG estimates of gestational maturity without knowledge of obstetric, neonatal, or ultrasonographic criteria. Thirteen recordings from this cohort were obtained on very premature neonates (i.e., < 32 weeks estimated gestational age). Fetal ultrasonographic determinations of gestational maturity for these 13 subjects were also obtained prior to birth. Ultrasonographic estimates were assigned without knowledge of other clinical data. Gestational age estimates based on electroencephalographic analyses were compared with 5 ultrasonographic estimates of gestational age maturity using multivariate regression (i.e., biparietal diameter, abdominal circumference, femur length, transcerebellar diameter, and head circumference), as well as the mother's last menstrual period. No significant differences were detected between the electrographic and obstetric/ultrasonographic estimates of gestational maturity. An electroencephalographer's assessment of gestational age is as accurate as the fetal ultrasonographic estimates in the asymptomatic preterm neonate whose gestational age is < 32 weeks at birth. PMID- 7880336 TI - Corpus callosum in developmentally retarded infants. AB - The development of the corpus callosum was examined by magnetic resonance imaging in developmentally retarded infants ranging in age from 1-13 months. Results were compared with those of normal infants. Eighteen magnetic resonance imaging studies were performed on 18 developmentally retarded infants. Fifty-four magnetic resonance imaging studies were performed on 38 normally developed infants. The thickness of the corpus callosum was measured at a point one-third of the length of the entire corpus callosum from the most anterior aspect of the genu. The development of the corpus callosum was related to aging in both groups. There was significant difference in the thickening of the corpus callosum between normal and developmentally retarded infants. PMID- 7880338 TI - Dopa-responsive dystonia simulating cerebral palsy. AB - Five patients presented in infancy or early childhood with various combinations of pyramidal and extrapyramidal signs with normal cognitive function. Their perinatal courses were unremarkable. In each patient, initial impressions listed by several examiners included spastic diplegia or cerebral palsy. Later in each course, either extrapyramidal features or progression suggested dopa-responsive dystonia. In 4 of the 5 children, cerebrospinal fluid was obtained and disclosed reduced levels of biopterin, neopterin, and homovanillic acid in all 4. Levodopa therapy resulted in prompt improvement with normal function returning within 6 months. The disappearance of the "spasticity," extensor plantar responses, and extrapyramidal signs, following levodopa therapy, confirmed the diagnosis of doparesponsive dystonia in these patients. Three had apparently sporadic disease; the other 2 were siblings with an affected paternal grandmother. Three had onset in infancy with delayed sitting and walking before the appearance of overt dystonia; infantile onset is infrequent in dopa-responsive dystonia. The other 2 had normal milestones, but developed gait disorders with prominent imbalance in early childhood. The diagnosis of dopa-responsive dystonia should be considered in children with unexplained or atypical "cerebral palsy." PMID- 7880337 TI - Cerebral dysgenesis and lactic acidemia: an MRI/MRS phenotype associated with pyruvate dehydrogenase deficiency. AB - Pyruvate dehydrogenase complex (PDHC) is an intramitochondrial multienzyme complex essential for the aerobic oxidation of glucose. The majority of patients with PDHC deficiency have abnormalities in the major catalytic and regulatory subunit, E1 alpha, which is encoded on the X chromosome. The clinical spectrum of PDHC deficiency is heterogeneous, particularly in heterozygous females, and diagnosis may be difficult. Three affected infant girls with PDHC deficiency were investigated. All had dysmorphic features, microcephaly with profound global developmental delay, and hypotonia. Systemic acidosis was absent, although serum lactate and pyruvate were abnormally elevated. Magnetic resonance imaging revealed hypoplasia of the corpus callosum in all patients. Proton magnetic resonance spectroscopy of brain revealed large increases in relative signal intensities for lactic acid and decreases in the relative signal intensities of N acetylaspartate, a marker of neuronal damage or less. Phosphorus MRS of muscle revealed abnormally low phosphorylation potentials for all these patients, although the degree of abnormality was variable and not directly correlated with the amount of brain lactate. It is proposed that cerebral dysgenesis and cerebral lactic acidemia as shown by magnetic resonance imaging and proton magnetic resonance spectroscopy are useful diagnostic clues to PDHC deficiency, particularly in females in whom variable patterns of X-inactivation reduce sensitivity of laboratory diagnosis based on the biochemical studies of peripheral tissues. In addition, muscle bioenergetic abnormalities in conjunction with CNS dysfunction may contribute to profound hypotonia in this disorder. PMID- 7880339 TI - Restless legs syndrome in childhood and adolescence. AB - Restless legs syndrome (RLS) is believed to be a condition primarily of middle to older age. However, it can have its onset in childhood. Five illustrative case histories with an autosomal dominant mode of inheritance are described. A mother and her 3 children (age: 6 1/2, 4 and 1 1/2 years) as well as a 16-year-old patient from a second family have typical RLS signs of leg discomfort (paresthesias) and motor restlessness prevalent at night and at rest, with temporary relief by activity. Polysomnography or videotaping revealed periodic limb movements in sleep (PLMS) and, in some cases, involuntary jerking of the legs was present during wakefulness as well. Clinicians should be aware that RLS can occur in childhood and adolescence and may be more common than heretofore recognized. "Growing pains" and attention deficit hyperactivity disorder (ADHD) are in the differential diagnosis of RLS in childhood. PMID- 7880340 TI - West syndrome following deep hypothermic infant cardiac surgery. AB - Postoperative seizures are among the more common complications of cardiac surgery in children. These seizures have traditionally been considered benign, transient phenomena with little, if any, prognostic significance. We report 4 infants with early postoperative seizures following cardiac surgery who later developed the previously unreported complication of West syndrome, with infantile spasms, hypsarrhythmia, and developmental delay. This group constitutes 6% of 67 infant spasms evaluated over a 5-year period at Boston Children's Hospital. The postoperative seizures in these 4 patients were more difficult than usual to control with antiepileptic therapy; otherwise no intra- or perioperative features distinguished these infants who later developed West syndrome from infants with apparently benign "postpump seizures." PMID- 7880341 TI - Vertebral artery dissection with bilateral hemiparesis. AB - Right vertebral artery dissection after trauma, with subsequent cerebellar and thalamic infarcts, is described in a 5-year-old child who presented with mild hemiparesis and ataxia. This vascular injury has been more commonly reported in adults. The diagnosis was confirmed with magnetic resonance imaging of the brain and cerebral magnetic resonance angiography. An arterial thrombus with multiple embolization was the cause of the child's neurologic deficits. Traumatic injury to the posterior circulation should be considered in children who have signs of vertebrobasilar insufficiency. PMID- 7880342 TI - Fetomaternal hemorrhage as an etiology of neonatal stroke. AB - We report a term infant who presented with focal seizures and was diagnosed with a large left hemispheral infarct. Evaluation revealed extensive fetomaternal hemorrhage and subsequent neuroimaging disclosed a classic border zone infarct consistent with a hypoperfusion injury. We postulate that fetomaternal hemorrhage should be considered in the differential causation of neonatal stroke. The unilaterality of the lesion in this patient is difficult to explain. PMID- 7880343 TI - Tonic "seizures" in a patient with brainstem demyelination: MRI study of brain and spinal cord. AB - Tonic seizures are a poorly understood manifestation of demyelinating disease, first reported in 4 patients with multiple sclerosis. We describe a patient with tonic extension of the left limbs caused by a right-sided brainstem lesion as the first manifestation of demyelinating disease. A 19-year-old man was referred with a 4-month history of spontaneous attacks of mild paresthesias of the left arm and leg, followed by 15-45 s of rigid extension of the left limbs, occurring up to 25 times per day. Two months after onset, an MRI scan revealed areas of T2 abnormality in the lateral right cerebral peduncle and deep frontal white matter. The EEG was normal, including during hyperventilation which induced a typical episode. All attacks were successfully suppressed by carbamazepine, phenytoin, and valproate monotherapy. Serologic testing for toxoplasmosis, cytomegalovirus, Epstein-Barr virus, Lyme disease, and HIV was negative. Cerebrospinal fluid oligoclonal bands were absent but cerebrospinal fluid immunoglobulin G was mildly elevated (4.2 mg/dl). Over the next 30 months, serial MRIs revealed a normal spinal cord and persistence of the midbrain lesion, with resolution of some of the white matter lesions but reappearance of others. At 46 months, the midbrain lesion resolved on MRI, and the spasms no longer occurred spontaneously, nor could they be elicited by hyperventilation. While two previous reports have shown internal capsule lesions to underlie the tonic spasms in demyelinating disease, this is the first report in which a brainstem lesion has been causative. PMID- 7880344 TI - Congenital muscular dystrophy with syringomyelia. AB - We report a 7-year-old boy with congenital muscular dystrophy with severe spinal deformation and low thoracic syringomyelia, which may represent a novel form of the disease with muscle involvement and spinal cord anomaly. We suggest that patients with congenital muscular dystrophy who manifest skeletal anomalies undergo spinal magnetic resonance imaging to detect potential spinal cord abnormalities, in addition to cranial magnetic resonance imaging to detect potential cerebral malformations. PMID- 7880345 TI - Episodic spontaneous hypothermia with hyperhidrosis. PMID- 7880346 TI - Meningitis and corticosteroid administration. PMID- 7880347 TI - Arthroscopic management of postoperative arthrofibrosis of the knee joint: indication, technique, and results. AB - From October 1987 through March 1991, 58 patients with postoperative joint stiffness underwent arthroscopic fibroarthrolysis. Forty-six knees in 46 patients were followed. The indication for arthroscopic management was decreased range of motion after surgery. Eighty-seven percent had been treated by arthrotomy. Thirteen percent had been managed by arthroscopic surgery. The indication for primary surgery was a torn anterior cruciate ligament in 74%. The mean interval between arthroscopic fibroarthrolysis and follow-up was 22.1 months. The average age was 32.7 years. A modified Blauth and Jager score was used for classification of fibroarthrosis: grade I (mild 17.4%), grade II (moderate 63%), grade III (severe 15.2%), and grade IV (bad 4.3%). The gain in range of motion was evaluated by the Cauchoix index: the results were excellent in 54.5%, good in 21.7%, and fair and poor in 23.8%. Pain was evaluated according to a modification of the Lysholm score: 80.4% of the patients experienced a reduction in pain. The sports activity level in the Tegner activity scale increased from 2.3 to 4.8. Patient satisfaction was excellent or good in 56.5% (n = 26), fair in 39.1% (n = 18), and poor in 4.3% (n = 2). On the basis of our retrospective study, we feel that arthroscopic fibroarthrolysis is of benefit to the patients with postoperative joint stiffness even after a prolonged period. PMID- 7880348 TI - Capsular elasticity and joint volume in recurrent anterior shoulder instability. AB - It is commonly claimed that unstable shoulders have an altered capsular elasticity and increased joint volume. To find out if there is a correlation between anterior instability and increased joint volume, 20 patients were examined while undergoing arthroscopic surgery of the shoulder. There were four anterior subluxators, 11 anterior dislocators, and five bilateral dislocators, and in all patients the contralateral shoulder was also examined. During continuous saline infusion, a pressure/volume curve was recorded within the range of 0-180 mm Hg. Joint volume was correlated with body surface area. Among the 15 patients with unilateral instability, there was no correlation between joint volume and body surface area. There were no differences in joint volume or capsular elasticity between the healthy and the unstable shoulder in any patient. It is concluded that capsular elasticity and joint volume contribute little to anterior shoulder instability and that instability probably depends more on damage to other stabilising structures in the joint. PMID- 7880349 TI - Arthroscopic anatomy of the lateral elbow: a comparison of three portals. AB - Ten fresh cadaveric elbows were used to evaluate the proximity of the radial nerve and its branches to three anterolateral portals. A proximal anterolateral portal used routinely at our institution and located 2 cm proximal and 1 cm anterior to the lateral epicondyle was compared with the distal anterolateral portal described by Andrews and with a mid-anterolateral portal. The three portals were initially established without joint distention while the elbows were flexed 90 degrees. Measurements were then obtained with and without joint distention at flexion angles of 0 degrees and 90 degrees. The radial nerve was found to be an average distance of 3.8 mm at extension and 7.2 mm at 90 degrees of flexion from the distal anterolateral portal, located 3 cm distal and 1 cm anterior to the lateral epicondyle. Conversely, the distance between the proximal anterolateral portal cannula and the nerve was statistically greater (p < 0.05), averaging 7.9 mm in extension and 13.7 mm in flexion. The remaining anterolateral portal, located 1 cm directly anterior to the lateral epicondyle, was found to be at a statistically greater average distance from the nerve than was the distal anterolateral portal but statistically closer than was the more proximal portal. The ability to visualize the joint arthroscopically was assessed using the three portals, and although the ulnohumeral joint could be adequately seen using all portals, radiohumeral joint visualization was most complete and technically easiest using the most proximal portal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880350 TI - Posterior portals for arthroscopic surgery of the knee. AB - Posterolateral and posteromedial portals are necessary for certain arthroscopic procedures of the knee. Many surgeons hesitate to use portals. A cadaveric study was performed to identify the structures at risk in establishing these portals. These include the saphenous vein and nerve, popliteal vessels, lateral superior and inferior genicular arteries, and peroneal nerve. Two basic techniques can be used to visualize the posterior compartments--from the same side or diagonally across the intracondylar notch. A clinical review of 179 patients in which posterior portals were used showed no serious complications. In three cases there was residual numbness in the distribution of the saphenous nerve and in two cases the saphenous vein was punctured. In three cases, the posterior compartments could not be safely visualized. In 87 cases the posterior compartment was visualized from the ipsilateral side; in the remaining 92 cases we used the contralateral technique placing the arthroscope diagonally across the intracondylar notch. PMID- 7880351 TI - Comparison of "catheter" and conventional arthroscopy in the diagnosis of knee derangements. AB - The diagnostic efficiency of the Optical Catheter System (OCS), which uses a 1.7 mm arthroscope, was compared with that of conventional arthroscopy in 50 patients with various knee derangements in standard arthroscopic conditions. Correct diagnoses were obtained with the OCS in 98% of anterior cruciate ligament derangements--92%-98% of those involving the medial and lateral meniscus, respectively--and 96% of cartilage disorders. No false-positives were noted for anterior cruciate ligament and meniscus injuries. False-negatives were caused by abundant intraarticular bleeding (no tourniquet was applied) and peripheral meniscus tears and false-positives by synovial superposition resulting in a mistaken diagnosis of patellar chondromalacia. The OCS proved a good diagnostic tool. Its employment, especially in an outpatient setting, should be restricted to a small number of patients and entrusted to expert arthroscopists. PMID- 7880352 TI - Knee pain diagrams: correlation with physical examination findings in patients with anterior knee pain. AB - All new patients who presented with knee problems were asked to fill out standard knee pain diagrams before being evaluated. Completed diagrams were not seen by the examining physicians. After obtaining the history and performing the physical examination, one of four physicians marked an identical diagram with the areas of tenderness. Ninety patients with a provisional diagnosis of patellofemoral pain completed 109 (19 bilateral) pain diagrams. Evaluation of the diagrams was quantitated by division of the diagrams into nine zones. The researcher grading the diagrams was blind to whether the diagrams were drawn by the patient or physician. Patients marked an average of 4.23 zones per knee compared with 2.66 zones for physicians. In 88% (96 of 109) of the knees, the physician diagram included all or some of the zones marked by the patients. Eighty-five percent of all zones marked by physicians were included in patient diagrams. Eighty-six percent of negative patient zones correctly predicted a negative examination. Overall frequency of positive findings in each of the nine zones was consistent between patient and physician diagrams. A physician can be confident that findings of tenderness will likely be within zones marked by a patient on a standard diagram of the knee. Pain diagrams facilitate proper diagnosis by correctly directing attention to areas of tenderness in a large percentage of cases and provide an inexpensive and highly useful prediction of areas of anterior knee tenderness in patients with patellofemoral pain. PMID- 7880353 TI - Outcome from day-case knee arthroscopy in a major teaching hospital. AB - Outcome is presented for 465 knee arthroscopies performed under general anesthesia in a public teaching hospital day surgery unit. The unanticipated hospital admission rate on the day of surgery was 1.07%. There were 11 (2.37%) major complications in the combined perioperative and postdischarge periods (up to 4 weeks postdischarge). Surgery-related complications (incidence 1.08%) were more frequent than complications of anesthesia (0.65%). Four patients (0.86%) had delayed complications after discharge that required hospital readmission. Stepwise polychotomous logistic regression showed that these complications were not significantly related to patient age, sex, American Society of Anesthesiologists (ASA) status or type of surgery. Mean recovery times required for patients to sit out of bed and to be ready for discharge were 61 +/- 37 and 142 +/- 52 min, respectively. Both postoperative pain and postoperative nausea and vomiting, present in 76% and 11.5% of patients, respectively, significantly delayed patient recovery, with longer delays associated with nausea and vomiting. Times required for patients to be ready for discharge were not correlated to either patient age (r = 0.07; p = 0.15) or duration of procedure (r = 0.07; p = 0.13). At early follow-up, 4.7% and 2.5% of patients had presented to hospital accident and emergency departments and local family doctors, respectively, usually for minor problems. Ninety-nine percent of all patients were happy with the ambulatory surgery service. With careful patient assessment and selection, day-case knee arthroscopy in a teaching hospital can provide satisfactory outcome. PMID- 7880354 TI - Refixation of large chondral fragments on the weight-bearing area of the knee joint: a report of two cases. AB - In most cases of cartilage avulsion, the chondral fragments are severely damaged, and refixation is therefore impossible. We present two cases with large intact cartilage fragments from the weight-bearing area of the femoral condyle after patellar dislocation. We tried refixation using fibrin sealant (Tisseel-Kit, Immuno AG, Vienna, Austria) and polydioxanone-pins (Bio-fix-Pins, Miracon AB, Helsingborg, Sweden). At second look arthroscopy, we found only one third to one half of the defects healed. Due to these results, the refixation of chondral fragments without attached bone seems to be questionable. PMID- 7880355 TI - Magnetic resonance imaging (MRI) and arthroscopy in the detection of meniscal degenerations: correlation of arthroscopy and MRI with histology findings. AB - In a prospective double-blind study, the capability of magnetic resonance imaging (MRI) and arthroscopy in the detection and grading of meniscal degenerations is evaluated by correlating MRI findings and arthroscopic diagnoses with a histologic grading model. In 82.8% of our results, grading based on MRI studies corresponded with the histologic grading classification. In 12 instances a meniscal degeneration verified at light microscopy was not detected at MRI, whereas in 15 cases tomography yielded a false-positive result. The overall accuracy was calculated to be 0.93 with a specificity of 0.79 and a sensitivity of 0.96. Concerning the evaluation of meniscal degenerations, MRI provides a positive predictive value of 0.95 and a negative predictive value of 0.82. Compared with the diagnostic specificity of the anterior and posterior zones, that of the intermediate segment of the meniscus is significantly reduced (p < 0.001). At arthroscopy, meniscal degenerations were diagnosed with an overall accuracy of 38.8%, a sensitivity of 27.5%, and a specificity of 75.5%. In 80 cases of grade 3 abnormalities, five false-negative diagnoses were made initially. These results suggest that MRI offers a valuable diagnostic potential providing reliable information about the internal consistency of the meniscus complementary to diagnostic arthroscopy. PMID- 7880356 TI - 3D MRI volume sizing of knee meniscus cartilage. AB - Meniscal replacement by allograft and meniscal regeneration through collagen meniscal scaffolds have been recently reported. To evaluate the effectiveness of a replaced or regrown meniscal cartilage, a method for measuring the size and function of the regenerated tissue in vivo is required. To solve this problem, we developed and evaluated a magnetic resonance imaging (MRI) technique to measure the volume of meniscal tissues. Twenty-one intact fresh cadaver knees were evaluated and scanned with MRI for meniscal volume sizing. The sizing sequence was repeated six times for each of 21 lateral and 12 medial menisci. The menisci were then excised and measured by water volume displacement. Each volume displacement measurement was repeated six times. The MRI technique employed to measure the volume of the menisci was shown to correspond to that of the standard measure of volume and was just as precise. However, the MRI technique consistently underestimated the actual volume. The average of the coefficient of variation for lateral volumes was 0.04 and 0.05 for the water and the MRI measurements, respectively. For medial measurements it was 0.04 and 0.06. The correlation for the lateral menisci was r = 0.45 (p = 0.04) and for the medial menisci it was r = 0.57 (p = 0.05). We conclude that 3D MRI is precise and repeatable but not accurate when used to measure meniscal volume in vivo and therefore may only be useful for evaluating changes in meniscal allografts and meniscal regeneration templates over time. PMID- 7880357 TI - Usefulness of magnetic resonance imaging for detecting intrasubstance tear and/or degeneration of lateral discoid meniscus. AB - In order to determine the usefulness of magnetic resonance imaging (MRI) for detection of intrasubstance tears or degeneration of the lateral discoid meniscus, we compared findings obtained with MRI with those of histological examination. Sixty-four symptomatic lateral discoid menisci were studied using MRI before surgical treatment. Of these, 18 (28%) met the criteria that MRI signals did not extend to the surface and that no visible tears were observable at arthroscopy. Findings of intrameniscal regions of high signal intensity and flattening in shape on MR images were found to represent intrasubstance tears or degeneration not detected at arthroscopy. Our findings thus demonstrate that MRI is more sensitive than arthroscopy in the detection of intrasubstance pathologies of the lateral discoid menisci. PMID- 7880358 TI - Meniscal lesions treated with suture: a follow-up study using survival analysis. AB - Fifty-seven patients, 45 males and 12 females with a median age of 23 years (range 8-56), underwent meniscal refixation by suture from 1986 through 1991. We used an arthroscopic outside-in technique with PDS sutures through injection cannulas. Thirty-six knees were stable and 21 had anterior cruciate insufficiency, five of which were subjected to surgery concomitantly with patellar tendon reconstruction and two of which were subjected to surgery at a later occasion. Fifty-one patients could be evaluated at a follow-up time of 2 months to 5.5 years (median 1.5, mean 2), and calculations were made using the BMDP statistical package and the Kaplan-Meier survival analysis. No serious complications were encountered. Twenty patients (39%) have undergone reoperation because of meniscal rerupturing. At 5 years, the cumulative survival rate is 50%. Smaller (posterior) lesions healed better than did more extensive lesions. No statistical influence of factors such as medial or lateral localization, age of patient or lesion, present displacement of meniscus, instability of the knee, or experience of the surgeon was evident. PMID- 7880359 TI - Meniscal repair enhanced by an interpositional free synovial autograft: an experimental study in rabbits. AB - This report describes the methods and effectiveness of interpositional free synovial autografts (IPFSAs) in promoting the healing of lesions in the avascular portion of the knee joint meniscus in rabbits. Thirty-four specimens were divided into two groups: 17 in the study group and 17 in the control group. The medial meniscus of the left knee joint was excised in each rabbit, and an artificial longitudinal tear was created in the avascular zone of the meniscus. In the study group, an IPFSA was sewn into the tear with a single horizontal suture. In the control group, the tear was repaired without synovium in the same manner. The menisci were then implanted into the right knee joint in the respective animals. At intervals the animals were killed, and the menisci were examined grossly and microscopically. Three menisci were eliminated because they had become attached to the synovial wall. In the study group, the lesion completely healed by 4 weeks, except for one. The menisci in the control group never completely healed, particularly at the deeper levels of the lesion. At 8-16 weeks, autolysis of the specimens made microscopic examination difficult and unreliable in both groups. Based on these results, it has been concluded that an IPFSA can promote the healing process in the avascular zone of a torn meniscus in rabbits and that systemic vascularity to the synovium or the meniscus is not essential for healing to occur. PMID- 7880360 TI - The posterior cruciate ligament arthroscopic evaluation and treatment. AB - The posterior cruciate ligament (PCL) is an anatomically and biomechanically complex structure. PCL injuries are reported to occur in 1-40% of acute knee injuries, with isolated PCL tears less common that PCL tears combined with other ligament injuries. Diagnosis of PCL injuries requires a high index of suspicion, careful physical examination, imaging studies, and systematic arthroscopic evaluation. Surgical reconstruction is recommended for acute PCL tears combined with other ligament or structural injuries, and when there is a negative tibial step off in an isolated PCL tear. Isolated acute PCL tears with a positive tibial step off or flat tibial step off may be treated with rehabilitation and observation and reconstructed later if symptomatic. Arthroscopic techniques of PLC reconstruction are becoming more refined and reproducible and may increase the predictability of this surgery. Carefully documented pre- and postoperative evaluations are required to judge the effectiveness of PCL reconstructive procedures. PMID- 7880361 TI - Arthroscopic radial head excision. AB - Radial head excision is a commonly performed procedure used in the treatment of radial head disorders. Arthroscopic radial head excision has not been previously described in the literature. In this study we report the technique and results of arthroscopic excision of the radial head for posttraumatic arthritis. PMID- 7880362 TI - Lateral femoral condyle fracture after endoscopic anterior cruciate ligament reconstruction. AB - A case is described in which a coronal plane fracture of the lateral femoral condyle propagated through the femoral tunnel 2 months after endoscopic anterior cruciate ligament reconstruction. PMID- 7880363 TI - Arthroscopic retrieval of loose bodies. AB - Using an ordinary metallic suction tube through a separate puncture wound, we were able to retrieve a free-floating loose body by suction action. We facilitated its retrieval by using conveniently located grasping forceps. This combination reproduces the action of commercially available suction loose body forceps. PMID- 7880364 TI - The arthroscopic knot technique for fracture of the tibia in children. AB - A technique for arthroscopic treatment of anterior intercondylar eminence is described. This technique avoids the use of screws, making it unnecessary for a second operation to remove them. PMID- 7880365 TI - Menisectomy used to describe removal of meniscal tissue from the knee. PMID- 7880366 TI - Case report: revision anterior cruciate ligament reconstruction. PMID- 7880367 TI - An alternative health-care reimbursement system. PMID- 7880368 TI - Healthcare by Kennedy. PMID- 7880369 TI - The foot: ulcer and toenail debridement and pressure relief padding. PMID- 7880371 TI - The team approach: using hospital owned low air loss beds. PMID- 7880372 TI - Pouching principles and products. PMID- 7880370 TI - Clinical study: peristomal skin irritation in colostomy patients. AB - A prospective, controlled, clinical study was conducted to evaluate the effect of skin barriers and adhesives on the incidence of peristomal skin irritation. Colostomy patients eligible to participate were randomly assigned one of two sets of 10 one-piece pouching systems. At mid-study, after using the first 10 pouches, patients were allocated 10 pouches from the alternate pouching system. Each pouching system was worn for a maximum of 24 hours. One-hundred twelve patients were enrolled in the study. At baseline, 8 percent of patients had some erythema. At the end of the study period, 26 percent of patients exhibited signs of skin irritation. Patients were significantly more likely to develop skin irritation following use of the Karaya-based barrier than following use of the pectin-based barrier product (Wilcoxon Rank Sum Test, p < 0.01). Similarly, the type of tape used to secure the pouching system significantly influenced the incidence of skin irritation. Analysis of the change in skin condition as it relates to all evaluated variables; i.e. pouching system, stoma shape, stoma size, stoma length and irrigation, showed that only the type of product used was significantly associated with a change in skin condition. This is the first report of a controlled clinical study to evaluate the effect of pouching systems and patient/stoma variables on skin integrity in colostomy patients. These findings confirm that skin irritation can be a considerable problem, even in patients who use irrigation techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880373 TI - O/WM commentary: surgical dressing alert. PMID- 7880374 TI - DNA-binding properties of nitroarene oligopeptides designed as hypoxia-selective agents. AB - The DNA-binding properties of six candidate nitroarene-functionalized oligopeptides 8-13 (i.e. 5-nitrofuran, 2-nitroimidazole and 4-nitrobenzene derivatives) with potential hypoxia-selective activity, developed as analogues of the archetypal minor groove-binding ligands, netropsin 1 and distamycin 2, have been examined using an extended molecular mechanics and dynamics (MM/MD) modelling approach. The energies calculated for interaction with the d(CGCGAATTCGCG) duplex, or d(CGCAAATTTGCG)2 in the case of the elongated nitrobenzene 13, correlate with fluorimetric data obtained by indirect competitive displacement of ethidium bromide from double-stranded calf thymus DNA. The results suggest that the mode of interaction for these agents resembles the behavior of structurally unrelated bis(amidine) derivatives that also bind to AT-rich stretches of duplex B-DNA via the minor groove. Analysis of the binding behaviour indicates that the interactions are determined by enthalpic rather than entropic energy terms, suggesting that specific or differential hydration effects for the DNA and ligand may be unimportant. A rational structure-activity relationship is established for the interaction of this family of oligopeptides with DNA that also encompass the bis(amidine) class of ligands. PMID- 7880375 TI - Tetravalent platinum complexes with ammine/amine carrier ligand configuration: circumvention of platinum resistance in vivo. AB - A platinum(II) and three platinum(IV) ammine/cycloalkylamine homologous series, the latter possessing either chloro, acetato or hydroxo axial ligands, were evaluated for efficacies in mice bearing tumor cells sensitive (leukemia L.1210/0 and reticulosarcoma M5076) or resistant to cisplatin (L1210/DDP) and tetraplatin (L1210/DACH). Within each series, which contained four homologs, potency increased (optimal dose decreased) as alicyclic ring size increased incrementally from cyclopropane to cyclohexane. All analogs were active at maximally tolerated doses against L1210/0 (%T/C = 125-426), with good associated therapeutic ratios of 2 to > 8 that, like the therapeutic index, provided indications of the drug's safety margin. Most complexes had activities that were similar to cisplatin (%T/C = 239) and tetraplatin (%T/C = 310). Antitumor activities were seen for all four platinum(II) complexes against L1210/DDP cells (%T/C = 133-167). In the three platinum(IV) series, on the other hand, only cyclopentane (C5) and cyclohexane (C6) analogs met or exceeded the minimum criterion for activity. These activities were similar to that seen with the positive control agent tetraplatin (%T/C = 133), but higher than that of cisplatin (%T/C = 94). Long-term survivors, which were frequently observed with these complexes in the L1210/0 model, were also seen in the L1210/DDP model, but to a lesser extent. Against L1210/DACH cells, which were sensitive to cisplatin (%T/C = 155), but resistant to tetraplatin (%T/C = 113), the C5 and C6 congeners in the platinum(IV) series were effective with %T/C in the range 148-189, while corresponding members in the platinum(II) series were only marginally active. In the solid M5076 model, complexes C5 in platinum(II) and in the acetato- and hydroxoplatinum(IV) series, and C6 from the hydroxo-platinum(IV) series, were as effective or more effective than cisplatin, which itself gave a tumor growth delay of 27.5 days. In summary, the results indicate that alicyclic ring size and, in the platinum(IV) series, axial ligand, are important modulators of efficacies of ammine/cycloalkylamine platinum congeners in both sensitive and platinum-resistant models. However, the cyclopentylamine or cyclohexylamine carrier ligand with acetato or hydroxo axial ligands in the platinum(IV) configuration are optimal combinations for circumventing both cisplatin and tetraplatin resistances. PMID- 7880376 TI - Structure-activity relationship of a series of nitrogen mustard- and pyrrole containing minor groove-binding agents related to distamycin. AB - Two series of tethered nitrogen mustards based on the minor groove-binding and A/T sequence-specific natural product distamycin have been synthesized and evaluated. The conjugates, which have a modified dimethylamino C-terminus, are comprised of one, two or three pyrrole carboxamide units linked to either benzoic acid mustard (BAM) or chlorambucil (CHL). The DNA binding properties, in vitro cytotoxicities and DNA cross-linking abilities were determined for each of the conjugates. The conjugates were found to bind preferentially to poly(dA.dT) compared to poly(dG.dC) DNA by ethidium displacement and circular dichroism. The di- and tripyrrole conjugates had higher binding affinities than the monopyrrole conjugates. All the conjugates were more cytotoxic than the nitrogen mustards themselves. Cytotoxicity increased with the increase from one to three pyrrole units and the CHL conjugates were more cytotoxic than the corresponding BAM analogues. The CHL conjugates were able to cross-link plasmid DNA at a 10-fold lower dose than CHL itself. The BAM conjugates showed < 10% cross-linking at doses which gave 100% cross-linking with the CHL conjugates. In cells, the CHL conjugates showed significant cross-linking at the IC50 values, while the BAM conjugates showed no evidence of cross-link formation even at 10 times the IC50 value. These results are discussed in reference to a series of previously reported GC-recognizing imidazole analogues possessing the same nitrogen mustard groups. PMID- 7880377 TI - Benzimidazo[1,2-c]quinazolines: a new class of antitumor compounds. AB - A series of substituted benzimidazo[1,2-c]quinazolines have been synthesized. This class of compound has been designed by structural comparison with other intercalator patterns. The determination of in vitro activities has shown high inhibitory values. PMID- 7880378 TI - Synthesis and biological evaluation of phosphate triester alkyl lysophospholipids (ALPs) as novel potential anti-neoplastic agents. AB - Phosphate triester derivatives of the anti-neoplastic alkyl lysophospholipids (ALP) have been prepared as novel potential therapeutic agents. In particular, simple, symmetrical phosphate triesters have been prepared, using phosphorochloridate chemistry. The compounds have been fully characterized by a range of techniques, and assayed for their inhibition of DNA synthesis by mammalian cells in culture. The compounds are generally inhibitory towards DNA synthesis in the micromolar range. However, the magnitude of the effect varies greatly with the phosphate structure. In particular, there is a clear trend towards decreasing activity with increasing alkyl chain length. Thus, short-chain dialkyl phosphate esters appear more effective than the reference compound hexadecyl phosphatidyl choline. PMID- 7880379 TI - Intracellular enhancement of intact antisense oligonucleotide steady-state levels by cationic lipids. PMID- 7880380 TI - Signalling targets for the development of cancer drugs. PMID- 7880381 TI - Immunology today online. PMID- 7880382 TI - The immunology of exceptional individuals: the lesson of centenarians. AB - Centenarians are the best example of successful ageing, since they have escaped the major age-associated diseases, and most are in good mental and physical condition. Here, Claudio Franceschi and colleagues discuss how the study of their immune systems reveals that several immune parameters are well conserved, suggesting that a complex remodelling of most immune parameters occurs with age, rather than a unidirectional deterioration. PMID- 7880383 TI - Extrathymic intestinal T-cell development: virtual reality? AB - Extrathymic T-cell development is a topic of considerable interest and debate, with important implications for the mechanisms of T-cell maturation and repertoire selection. Recent evidence has suggested that intraepithelial T lymphocytes (IELs) of the small intestine can mature and undergo selection in the absence of a thymus. However, IEL precursors are present in the thymus and IEL development is known to be influenced by the thymus. Here, Leo Lefrancois and Lynn Puddington discuss these data and suggest that the differentiation pathway of IEL precursors is dependent on whether or not a thymus is present. PMID- 7880384 TI - Recent advances in the study of dendritic cells and follicular dendritic cells. PMID- 7880385 TI - The production of cytokines by polymorphonuclear neutrophils. AB - Cytokines orchestrate the complex network of cellular interactions that regulate effector cell functions of natural and immune resistance. Although T cells, natural killer (NK) cells and monocytes/macrophages are the main producers of cytokines, a number of reports in the last few years have demonstrated that polymorphonuclear neutrophils (PMN) also have the ability to synthesize and release immunoregulatory cytokines. Here, Marco Cassatella describes novel facets of the regulation of cytokine production by PMN that highlight the involvement of of PMN in cell-cytokine crosstalk. PMID- 7880386 TI - Is atherosclerosis an immunologically mediated disease? AB - In contrast to general beliefs, recent data from different laboratories have provided evidence that the first stages of atherosclerosis are of an inflammatory nature. Here, Georg Wick and colleagues suggest that an autoimmune reaction against heat shock protein 60 (Hsp60), expressed by endothelial cells in areas that are subject to increased haemodynamic stress, is the initiating event in atherogenesis. Humoral and T-cell-mediated immune responses against Hsp60 have both been demonstrated early in disease. This inflammatory stage, which is reversible and has even been found in children, may progress into fully developed atherosclerotic lesions, displaying all the classical pathohistological and functional consequences, if additional risk factors such as high blood cholesterol levels, smoking and obesity, are present. PMID- 7880387 TI - Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. AB - CD4+ T cells play a key role in regulating immune system function. When these regulatory processes go awry, organ-specific autoimmune diseases may develop. Here, Roland Liblau, Steven Singer and Hugh McDevitt explore the thesis that a particular subset of CD4+ T cells, namely T helper 1 (Th1) cells, contributes to the pathogenesis of organ-specific autoimmune diseases, while another subset, Th2 cells, prevents them. PMID- 7880388 TI - Viro-immunopathogenesis of HIV disease: implications for therapy. PMID- 7880389 TI - Comment on Mosier and Sieburg. PMID- 7880390 TI - MHC: orchestrating the immune response. PMID- 7880391 TI - [Progress report for the period 1 January 1992--31 December 1993]. PMID- 7880392 TI - Selected papers from the annual meeting of the Society for Gynecologic Investigation. Chicago, Illinois, March 22-26. PMID- 7880393 TI - Use of lymphocyte platelet binding assay for detecting a preimplantation factor: a quantitative assay. AB - PROBLEM: To evaluate the ability of the lymphocyte/platelet binding assay to identify a preimplantation factor (PIF). METHOD: Percentages of binding of lymphocytes by platelets in the presence of sera from 30 known pregnant and 30 nonpregnant individuals were compared using a novel lymphocyte/platelet binding assay. The assay is performed using a combination of a heat inactivated sera with donor O+lymphocytes, activated complement and an antibody against CD2 (T11, Ortho Pharmaceuticals). RESULTS: In nonpregnant females (23.6 +/- 6.5%) and males (17.7 +/- 4.7%) the percentage of lymphocytes bound by platelets was significantly different from pregnant women (56.1 +/- 15.9%) (P < 0.0001). Serial sampling of blood in five women undergoing IVF/ET who had normal pregnancies showed the detection of PIF by 4 days after transfer. The lymphocyte/platelet binding assay was not influenced by hCG, progesterone and estradiol. The interassay and intrassay variabilities were < 3%. CONCLUSIONS: The lymphocyte/platelet binding assay is a simple, reproducible, specific and cost efficient assay for measurement of PIF. Application of this assay will provide investigative and diagnostic tools for identifying and monitoring early pregnancy events. PMID- 7880394 TI - Expression of intercellular adhesion molecule-1 (ICAM-1) on cultured human endometrial stromal cells and its role in the interaction with natural killers. AB - PROBLEM: Recent evidence emphasizes the role of natural killer cells (NKs) as potential effectors of peritoneal immune surveillance directed against the outgrowth of endometrial cells, refluxed with menstrual debris, in ectopic sites. This NK-mediated cytotoxicity toward autologous endometrial antigens seems to be significantly decreased in endometriosis patients. METHOD: We set up experiments to clarify which molecules are involved in NK-endometrial cell interaction. In particular, we evaluated the surface expression and functional activity of intercellular adhesion molecule-1 (ICAM-1), a cell surface glycoprotein that has been identified as one of the ligands for lymphocyte function-associated antigen 1 (LFA-1), present on almost all leucocyte cell types. Immunofluorescence flow cytometry was used to assess ICAM-1 expression on resting and IL 1 beta-activated endometrial stromal cells in culture. Dermal fibroblasts were used as control cells. Cytotoxicity and binding assays by 51Cr release in presence and absence of a specific monoclonal antibody (mAb) against ICAM-1 were then performed in order to determine the effect of this molecule on NK-mediated cytotoxic and binding activity toward endometrial stromal cells. RESULTS: The results of this study indicated that ICAM-1 expression on endometrial stromal cells seems to be constitutively higher than on dermal fibroblasts and can be up-regulated upon exposure to IL 1 beta. Furthermore, a mAb against ICAM-1 strongly inhibits the binding but not the cytotoxicity of NKs toward endometrial cells. No difference in the expression of this molecule was observed throughout the cycle. CONCLUSIONS: The presence of ICAM-1 on human endometrium might relate to the action of the immunocompetent cells in human specific reproductive events. PMID- 7880395 TI - Anti-ZP3 antibodies binding to the human zona pellucida: effect of oocyte-storage conditions. AB - PROBLEM: The zona pellucida protein 3 (ZP3) is a zona pellucida (ZP) glycoprotein crucially involved in fertilization. ZP3 plays a major role in sperm binding and induction of the acrosome reaction. In different species, ZP3 proteins differ in their primary structure as derived from cDNA clones. The hemizona assay (HZA) is a bioassay that evaluates binding of human sperm to human ZP and is highly predictive of fertilization outcome under in vitro conditions. METHOD: In these studies, we used antisera generated against synthetic ZP3 peptides to compare antibody binding patterns to ZP with sperm-ZP binding capacity under different HZA conditions. RESULTS: Analysis of antibody binding to hemizonae derived from metaphase II human oocytes that were used either after refrigeration at 4 degrees C or stored in a hyperosmotic salt solution revealed a strong reaction with human ZP3. However, treatment of human oocytes using a protocol to freeze embryos with the addition of 1,2 propanediol drastically reduced binding of ZP3 antibodies to the hemizonae. Nevertheless, no significant difference of sperm binding occurred under HZA conditions when oocytes were refrigerated, salt-stored, or frozen with 1,2 propanediol. CONCLUSIONS: Our results indicate that the ZP3 protein backbone might be altered by 1,2 propanediol-treatment while the glycoprotein-receptor remains intact. We conclude that antisera against ZP3 peptides can be used as markers for the ZP3 protein backbone in human oocytes and might be useful tools for the evaluation of ZP3 protein integrity. PMID- 7880396 TI - Myometrial expression of mRNA encoding epidermal growth factor receptor (EGFR) throughout the menstrual cycle. AB - PROBLEM: To investigate the quantitative changes in expression of EGFR mRNA in the myometrium throughout the menstrual cycle. METHOD: Myometrium was collected at hysterectomy from 27 women with a history of regular cycles. Total RNA (20 micrograms) was isolated and analyzed by Northern blot using a human EGF-R specific 32P-labeled cDNA probe. The hybridization signals were quantified by densitometry, standardized, and reported in densitometry signal units (DSU). Endometrial specimens from the same uteri were simultaneously evaluated for histologic dating of menstrual cycle day. EGFR gene expression in endometrium was previously reported. Statistical significance of the differences in myometrial gene expression between menstrual phases was evaluated by student's t test. RESULTS: EGFR mRNA was expressed in all myometrial tissues tested. Levels were higher in the late proliferative phase than in all other phases (P < .05). Women over 40 years old had lower proliferative phase expression than younger women. CONCLUSION: This data suggests that myometrial EGFR mRNA expression varies in association with the histologic phases of the normal menstrual cycle, and may be affected by aging, even when cycles occur at regular intervals. PMID- 7880397 TI - Immunosuppression by hydatidiform mole trophoblast is neutralized by monoclonal antibodies to beta-interferon. AB - PROBLEM: In sheep and cattle, trophoblast-derived interferons serve as signals for the maternal recognition of pregnancy and may regulate the immunologic relationship between the fetus and mother. METHOD: In this study, soluble extracts prepared from human hydatidiform mole decidua (DE) and trophoblast (HME) were screened for immunosuppressive activity using an interleukin (IL)-2 dependent T-cell line (CTLL2). Antibody neutralization studies were performed with monoclonal antibodies to alpha- and beta-interferon (IFN). RESULTS: HME suppressed (P < 0.05) IL-2-stimulated (2 IU/well) CTLL2 proliferation at doses ranging from 500 (52 +/- 2% of control) to 100 (74 +/- 5%) micrograms/ml concentrations. DE also suppressed (P < or = 0.05) CTLL2 proliferation in a dose related fashion from 500 (20 +/- 6% of control) to 100 (71 +/- 8%) micrograms/ml doses. Preincubation with the alpha- and beta-IFN antibody preparations had no effect on CTLL2 suppression by the DE sample. In contrast, the beta-IFN antibody partially neutralized the suppressive activity of HME at each of the dilutions tested. The monoclonal antibody to alpha-IFN failed to neutralize HME suppression at any of the doses tested. CONCLUSIONS: These results suggest that hydatidiform mole trophoblast produces a beta-IFN-like macromolecule that may abrogate maternal rejection responses that are harmful to the developing fetal allograft. PMID- 7880398 TI - Gestational age correlates with immunosuppressive properties of hydatidiform mole pregnancies. AB - PROBLEM: Soluble trophoblast extracts (HME) from some human hydatidiform mole pregnancies suppress IL-2-dependent T-cell proliferation, while others express no immunosuppressive bioactivity. This study was designed to determine if suppression by HME was correlated with gestational age, uterine size, or hCG secretion. METHOD: Soluble extracts were prepared from nine hydatidiform mole trophoblast samples and screened for immunosuppressive activity using a murine cytotoxic T-cell proliferation assay (CTLL-2). Gestational ages were determined from last menstrual cycle and uterine size was estimated at the time of surgery. Serum samples were collected prior to uterine evacuation and were assayed for human chorionic gonadotropin (hCG). RESULTS: Four of nine HME samples significantly (P < 0.05) suppressed CTLL2 proliferation, while five exhibited no suppressive activity. A strong positive correlation (r = 0.639) was noted for the relationship between gestational age of the molar pregnancies and interleukin-2 (IL-2)-stimulated CTLL2 proliferation (expressed as % of control) in the presence of HME (500 micrograms/mL). This indicates that HME suppression of CTLL2 proliferation is highest in early gestation and then declines with increasing gestational age. A similar correlation was observed between estimated uterine size at surgery and CTLL2 proliferation with added HME, although the association was not as strong (r = 0.359). No association was noted between hCG levels and CTLL2 proliferative responses (r = -0.091). CONCLUSIONS: The results of this study suggest that production of immunosuppressive factors by hydatidiform mole trophoblast is developmentally regulated, and decreases with advancing gestation. PMID- 7880399 TI - Nuclear regulation of HLA class I genes in human trophoblasts. AB - PROBLEM: Human trophoblast expression of class I human leukocyte antigen (HLA) genes is unique in that there is no classical gene expression, but nonclassical HLA-G is expressed and only by cytotrophoblast cells. This differential expression of classical versus nonclassical class I genes suggests tissue specific regulation. Recently, a negative regulatory element (NRE), 180 bp 5' to transcription initiation was identified in a murine embryonal carcinoma cell line that markedly inhibited class I gene expression (Flanagan et al., Proc Natl Acad Sci USA 1991; 83:3145-3149). METHOD: Here we analyzed the human HLA-A2 gene for a putative NRE sequence and determined whether such a sequence is capable of binding to factors present in a variety of class I-null cell lines. RESULTS: Sequence analysis revealed that the NRE for human HLA-A2 is identical to that for mouse H-2Ld. Using gel shift assays with nuclear extracts (NE) from a variety of cell types, we demonstrated specific binding to the HLA-A2 NRE sequence. The choriocarcinoma cell lines JEG and BeWo and the F9 cells (all negative for classical gene expression) contained this DNA binding factor(s). This binding factor was not present in NE from lymphocytes or a variety of other cell lines that were positive for classical gene expression. CONCLUSION: Human trophoblasts appear to have a tissue specific nuclear binding factor that may down regulate classical class I expression upon binding to the NRE sequence. The HLA-G gene does not have this NRE region thus enabling its expression by these cells. PMID- 7880400 TI - Characterization of lymphocyte subpopulations and T cell activation in endometriosis. AB - PROBLEM: Numerous studies have characterized the lymphocyte subpopulations in normal eutopic endometrium and suggested a role for the cytokine secretory products of these lymphocytes in regulating endometrial cell proliferation and differentiation. Recent studies have shown that ectopic endometrium contains a greater concentration of scattered stromal lymphocytes than does eutopic endometrium. However, the lymphocyte subpopulations and their activation status have not been characterized in ectopic endometrium. METHODS: We performed immunohistochemical studies on serial sections of proliferative and secretory phase eutopic endometrium and ectopic endometrium obtained during the proliferative phase using monoclonal antibodies to CD4 (T helper-inducer cells), CD8 (T cytolytic-suppressor cells), CD22 (B-cells), CD56 (natural killer cells), and VLA-1 (T-cell activation marker). RESULTS: Ectopic endometrium contained significantly more scattered stromal CD4, CD8, and activated T cells than did proliferative and secretory eutopic endometrium. There were more activated T cells in proliferative than in secretory eutopic endometrium. Ectopic endometrium contained significantly fewer NK cells than proliferative and secretory endometrium. CONCLUSIONS: These results demonstrate that (1) the increased lymphocyte population in ectopic endometrium is due to increased numbers of CD4 and CD8 cells, and (2) a greater number of activated T cells are present in ectopic endometrium as compared to eutopic endometrium. Increased concentration of stromal T cells and enhanced VLA-1 expression in ectopic endometrium suggest that cytokine products of the activated T-cells may be involved in regulating cellular processes of endometriosis tissue. PMID- 7880401 TI - Interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) in peritoneal fluid and macrophage-conditioned media of women with endometriosis. AB - PROBLEM: The presence of the various cytokines in human peritoneal fluid has been incompletely evaluated. Changes in cytokine levels may be related to activation of peritoneal macrophages, development of endometriosis, and infertility. This study assesses peritoneal fluid levels of interferon gamma (IFN-gamma) and interleukin-6 (IL-6), and peritoneal macrophage production of IL-6, in women with and without endometriosis. METHOD: Peritoneal fluid was obtained from 62 women at the time of diagnostic or operative laparoscopic surgery for benign gynecologic disease. Peritoneal macrophages were isolated, cultured for 24 h, and the culture media collected. IFN-gamma and IL-6 levels in peritoneal fluid samples and macrophage conditioned media were determined by commercial ELISA. RESULTS: IL-6 was significantly higher in the macrophage conditioned media of women with endometriosis as compared with controls. IL-6 levels were fourfold higher in early stage endometriosis (P < 0.05) and eightfold higher in advanced endometriosis. There were no significant differences between groups in the peritoneal fluid levels of IL-6 or IFN-gamma. CONCLUSIONS: Peritoneal macrophage IL-6 secretion is increased in women with endometriosis, and appears to correlate with disease stage. IFN-gamma does not appear to be responsible for the activation of macrophages in women with endometriosis. PMID- 7880402 TI - Organ culture of amniochorionic membrane in vitro. AB - PROBLEM: The purpose of the study was to develop a novel method of amniochorionic membrane culture aimed at maintaining tissue integrity. METHOD: Amniochorionic membranes were collected from women prior to labor, undergoing elective cesarean section, with no history of infection or pregnancy related complication. Fetal membranes were maintained in culture for up to ten days. Glyceraldehyde-3 phosphate dehydrogenase (GAPDH), a "house keeping" gene and inflammatory cytokine mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) at various periods of culture. mRNA localization was performed by in situ hybridization. RESULTS: GAPDH gene expression was seen throughout the culture period. Inflammatory cytokine mRNA (IL-1 alpha, IL-1 beta and IL-6) were also detected during culture. Cellular and tissue morphology appeared normal. CONCLUSIONS: The culture technique we propose is a simple organ explant system which maintains the morphology and autocrine/paracrine relationships within this tissue. PMID- 7880403 TI - Expression of TNF-alpha and TNFR p55 in cultured amniochorion. AB - PROBLEM: Preterm labor and PROM are major complications of pregnancy. We have reported the possible role of amniochorionic membrane as it relates to the production of cytokines and the early onset of labor. Amniochorion is capable of responding to an infectious process with the production of IL-6 and IL-1 beta. Here we examine the expression of TNF-alpha and TNFR in amniochorion. METHOD: Amniochorionic membranes were collected and maintained in an organ explant system. Samples were frozen and/or fixed for RT-PCR, in situ hybridization, and immunocytochemistry. RESULTS: RT-PCR demonstrated mRNA for TNF-alpha and in situ hybridization localized mRNA in chorion and amnion. Immunocytochemistry demonstrated TNF-alpha peptide in amnion but not in chorion. Immunocytochemical localization of TNFR indicates presence of that peptide in both amnion and chorion. CONCLUSIONS: We conclude that the fetal membranes are sources of TNF alpha and TNFR, supporting our previous work indicating that fetal membranes are active participants in the response to intraamniotic infection. PMID- 7880404 TI - The presence of cytomegalovirus antigens in karyotyped abortions. AB - PROBLEM: About one out of six pregnancies ends in spontaneous abortion before the 17th week. In more than half of these a chromosome abnormality is present, which explains the abortion. The role of cytomegalovirus (CMV) infections in early pregnancy failure is unclear. If there is a role for CMV, a preponderance of infections would be expected in a chromosomally normal group. METHOD: The significance of CMV in abortions has been studied by screening 80 spontaneous and nine induced abortions with known karyotype for the presence of phosphoprotein pp65, an early CMV antigen. Also, endometrial biopsies (n = 55) and menstruum (n = 10) were screened. In 11 patients more than one specimen was available for study. RESULTS: The protein was present in the glandular epithelium of the decidua of spontaneous as well as induced abortions in 31 of 89 (35%) cases, irrespective of chromosomal constitution. Trophoblastic cells were pp65 positive in 6/89 cases. A total of 17 embryos could be studied, seven of which were positive. Positive staining of embryonic organs correlated strongly with the presence of the antigen in the decidua. The endometrial biopsies and menstrual discharges from women of comparable ages showed the same percentages of positive tests for pp65: 35 and 20%. Histologically positive and negative specimens could not be differentiated other than by the specific staining. In 10 of 11 patients with more than one specimen available, the results were consistent. One patient had two positive and one negative specimen. CONCLUSION: The findings indicate that in early pregnancy cytomegalovirus is transmitted from the decidual glands to the foetus. However, we have not found indications that the presence of cytomegalovirus infection as shown by the presence of antigen is pathogenic for early pregnancy. PMID- 7880405 TI - Decreased beta-carotene levels in exfoliated vaginal epithelial cells in women with vaginal candidiasis. AB - PROBLEM: Women are more susceptible to vaginal candidiasis when the host immune response is suppressed. The antioxidant nutrient beta-carotene is postulated to possess immunoenhancing properties. The purpose of this study was to investigate beta-carotene concentrations in exfoliated vaginal epithelial (EVE) cells in women with vaginal candidiasis. METHODS: Beta-carotene levels in EVE cells, collected by a saline lavage technique from 22 women with vaginal candidiasis and 20 normal controls, were analyzed. The diagnosis of vaginal candidiasis was established by the presence of pruritus, white cheesy vaginal discharge, and a positive potassium hydroxide preparation. Beta-carotene levels were assayed using high pressure liquid chromatography. RESULTS: Vaginal cell concentrations of beta carotene were significantly decreased in women with vaginal candidiasis (P < 0.001). CONCLUSIONS: Decreased beta-carotene levels, and possibly other antioxidants, may alter the local immune response resulting in disturbances in the vaginal flora, overgrowth of candida, and the development of vaginal candidiasis. PMID- 7880406 TI - Protein phosphorylation pattern and role of products of c-erbB-1 and c-abl proto oncogenes in murine preimplantation embryonic development. AB - PROBLEM: To investigate the protein phosphorylation pattern and role of products of c-erbB-1 and c-abl proto-oncogenes with known tyrosine kinase activity in preimplantation embryonic development in mice. METHOD: The protein phosphorylation pattern was studied by in vitro 32P metabolic labeling of murine ova/embryos as well as by in vitro kinase assay performed directly on various ova/embryos extracts. The role of products of c-erbB-1 (170 kDa, receptor for epidermal growth factor [EGF]) and c-abl proto-oncogenes (150 kDa) was examined by in vitro culturing murine embryos in the presence of monoclonal antibodies to respective protein products and by co-culturing with EGF, the ligand for EGF receptor (EGF-R). RESULTS: In vitro metabolic labeling of murine ova/embryos showed 32P incorporation into at least two protein bands of murine ova (M(r) 81 and 36 kDa), six protein bands of two-cell (M(r) 81, 36; and 97, 52, 22 and 19 kDa, respectively), six protein bands of morula (M(r) 81, 36; 97, 22, and 19; and 33 kDa, respectively), and eight protein bands of blastocyst (81, 36; 97, 22, 19; and 115, 58, and 15 kDa, respectively), stage embryos; there were some specific bands in each stage. Prolonged labeling from 2 to 4 h not only resulted in a relative increase in 32P incorporation into these proteins but also revealed additional bands in morula (M(r) 133 and 115 kD) and blastocyst (M(r) 49, 33, and 31 kD) stage embryos. In vitro kinase assays performed directly on various ova/embryos extracts revealed at least three phosphoproteins (M(r) 58, 36 and 33, respectively) that were common to ova, two-cell, morula, and early/late blastocyst stage embryos. Additionally, three protein bands each in murine ova and two-cell embryos (M(r) 108, 81, 73 kDa, respectively), and four protein bands of late blastocyst (M(r) 108, 73; 133 and 18 kDa, respectively) stage embryos were also revealed. Culture of two-cell embryos in the presence of EGF, the ligand for EGF-receptor, resulted in a concentration dependent increase (P < .001) in the number of cells per blastocyst. Monoclonal antibody to c-erbB-1 170 kDa protein (receptor for EGF) did not affect development of in vitro cultured murine embryos from two-cell to morula, but significantly (P < .001) inhibited the in vitro development of morula to late blastocyst stage. Monoclonal antibody to c-abl protein inhibited the development of murine embryos from two-cell to morula (P < .017), as well as, from morula to late blastocyst stage (P < .002 to .01). CONCLUSIONS: These results suggest that the stage-specific protein phosphorylation pattern and specific products of c-erB-1 and c-abl proto oncogenes may have a role in preimplantation embryonic development in mice. PMID- 7880407 TI - Effects of GnRH antagonist on lymphocyte subpopulations in primary and secondary lymphoid tissues of female mice. AB - PROBLEM: GnRH analogs are playing an increasing role in the treatment of many clinical disorders. Recent studies have indicated that GnRH agonists suppress immune function in mice in vivo. The present study investigated the effects of GnRH antagonist of functional lymphocyte subsets of mice in vivo. METHOD: Three- and 10-wk old female mice received 10 micrograms of Nal-Glu daily for 15 and 30 days; changes in the immunophenotypic expression of lymphocytes from thymus, bone marrow, spleen and blood were analyzed by flow cytometry. RESULTS: The administration of GnRH antagonist to pre- and postpubertal female mice induced slight increases in lymphocyte subpopulations in primary and secondary lymphoid tissues. These effects are opposite those obtained with GnRH agonist in our earlier studies in mice. CONCLUSIONS: Assuming similar effects in humans and rodents, the gonadal steroid suppression achieved by GnRH antagonist treatment has no apparent suppressive effects on the immune system. PMID- 7880408 TI - Interleukin-6 does not stimulate rat myometrial contractions in an in vitro model. AB - PROBLEM: Interleukin-6 (IL-6) increases in culture-positive amniotic fluid in women with preterm labor. IL-6 stimulates the production of prostaglandins leading to increased uterine activity. METHODS: We tested the hypothesis that IL 6 increases myometrial activity through release of uterotonic mediators. We studied the effect of IL-6 on uterine contractions in the absence and presence of fetal membranes to determine if the effect was on myometrium alone or was mediated through fetal membranes/decidua. IL-6 in concentrations of 100, 10, 0.1 or 0 ng/ml was added to the maternal side of the dual chamber-fetal membrane uterine muscle in vitro model. RESULTS: We found that 10 ng/ml of IL-6 alone, without fetal membranes, caused a significant decrease in uterine contractions over time (P < or = 0.01). This decrease was not observed with the addition of term, nonlabored fetal membranes. CONCLUSIONS: IL-6 in the presence or absence of membranes, over a four log fold dose range, did not stimulate uterine contractions. PMID- 7880409 TI - Topical ketorolac has no antinociceptive or anti-inflammatory effect in thermal injury. AB - This study investigated the antinociceptive and anti-inflammatory effect of a topical non-steroidal anti-inflammatory drug in human thermal injury. Twelve healthy unmedicated volunteers had identical burn injuries produced on the medial side of both calves with a 49 degrees C 15 x 25 mm thermode. Ketorolac gel or placebo were randomly applied on the right or left calf 1.5 h before burn injury, immediately after burn injury and 6 and 12 h later in a double-blind trial where every subject served as his own control. Heat pain detection thresholds (HPDT), head pain tolerance (HPT), mechanical pain detection thresholds (MPDT) and the intensity of burn-induced erythema (erythema index, EI) were assessed in the area of the thermal injury, and areas of hyperalgesia to pin prick were determined outside the injury before and 3, 6 and 24 h after the burn injury. Burn injury led to a decrease in HPDT, HPT and MPDT, an increase in EI and development of mechanical hyperalgesia (P < 0.05). Ketorolac gel had no effect on any of the nociceptive or inflammatory variables studies (P > 0.2). PMID- 7880410 TI - T lymphocytes and immunosuppression in the burned patient: a review. AB - Extensive thermal trauma results in impaired immune function which has been attributed to a reduction in T lymphocyte numbers, increased suppressor cell activity, serum suppressive factors and altered cytokine synthesis and receptor expression on T cells. Numeric and phenotypic changes in T lymphocytes, T cell proliferation and functional responses of T lymphocytes in recent studies using murine models and patients are described. PMID- 7880411 TI - Sensory endings in skin grafts and scars after extensive burns. AB - Fifteen patients who underwent a split thickness skin graft operation for full thickness burns and six patients with postburn scars were biopsied after a standard aesthesiological examination completed with Weber and Dellon tests. A semiquantitative evaluation was performed on immunohistochemically stained sections to determine the presence or absence of PGP 9.5 immunoreactive intraepithelial fibres, complex sensory receptors, nerve fibres in the dermal papillae, vessel-innervating fibres, gland-innervating fibres, and nerve trunks in the deep dermis. The reinnervation pattern was similar in grafts and scars. With regard to sensory receptors, free nerve endings and Merkel-neurite complexes were observed. Statistical analysis suggested a significant correlation between sensibility and the amount of regenerated nerve structures (particularly in the epidermis and dermal papillae). PMID- 7880412 TI - Epidermal growth factor excretion in burned rats. AB - Evidence for epidermal growth factor (EGF) involvement in the physiological response to burns was sought from urinary levels of EGF, urea and creatinine in male rats using a standardized thermal skin injury model (25 per cent body surface) and treated with fluid resuscitation. Postmortem, the skin lesions were studied by microscopy to guarantee the absence of inflammatory complications. Statistically significant differences were observed in body weight, urea and creatinine excretion when compared to the basal values. When EGF excretion results were evaluated as raw data (expressed as ng/mg of creatinine or ng/day) compared to basal levels, no statistically significant differences were observed. However, when the results were expressed as percentage increases with respect to the basal values, a statistically significant increase was found over the first 7 days postinjury (P = 0.029). PMID- 7880413 TI - Staphylococcal toxic shock syndrome in a paediatric burn unit. AB - A case of staphylococcal toxic shock syndrome (TSS) in a 15-year-old patient undergoing reconstructive burn surgery is reported. This syndrome, first described in menstruating women using tampons, can also occur as a postsurgical complication. The epidemiology, microbiology, clinical presentation and management of non-menstrual TSS are discussed and correlated with the patient present. We advise caution in the use of occlusive dressings and recommend constant isolation of patients with open wounds colonized with a TSST-1 producing strain of Staph. aureus. PMID- 7880414 TI - Composite grafts of autogenic cultured epidermis and glycerol-preserved allogeneic dermis for definitive coverage of full thickness burn wounds: case reports. AB - In patients with extensive deep burns and scarce donor sites autogenic cultured epithelial grafts (auto-CEG) have become a real alternative. In deep burns the 'take' rate of auto-CEG applied directly on subcutaneous fat, fascia or muscle is unreliable and frequently disappointing. The auto-CEG seems to need a dermal base. Improved results have been reported when auto-CEG were applied to the dermal base of a viable cryopreserved donor skin. We extended this principle by using the dermal layer of non-viable glycerol-preserved donor skin (GPDS). We report on two patients with deep burns of 55 and 80 per cent TBSA in whom we used the composite grafting of auto-CEG on non-viable allogeneic dermis from GPDS. The estimated 'take' rates were 70 and 77 per cent. The grafted areas remained stable for 4 and 8 months respectively. The two-layer skin substitute gave a permanent cover for full thickness burn wounds of higher quality and better 'take' rate than previous results, where the auto-CEG had been grafted directly onto the debrided wounds. PMID- 7880415 TI - Enhanced amino acid uptake in both skeletal muscle and liver by burn plasma in rats. AB - The study was designed to test amino acid uptake in skeletal muscle after burn injury (up to 72 h). Also examined were the effects of plasma from burned rats over varying periods postburn (1-72 h), when plasma was added in vitro to incubated muscles and liver slices. Major burn injury (40 per cent total body surface area (TBSA)) was produced in male Sprague-Dawley rats weighing 60-80 g. Both soleus muscles were dissected intact at 1, 3, 6, 12, 24, 48 and 72 h postburn. Amino acid transport was measured by determining intracellular uptake of [3H] alpha-aminoisobutyric acid (AIB) during a 2 h incubation. In the second series of experiments, whole plasma from burned rats was added in vitro to incubated muscles and liver slices from healthy animals, and amino acid uptake was determined. AIB uptake in burned rat muscle was reduced by 24 per cent by 24 h postburn and 16 per cent by 48 h postburn. There was an increased effect from burn plasma on normal incubated muscles and liver slices, 72 per cent on muscles and 30 per cent on livers. Present results suggest an intrinsic decrease in amino acid uptake by muscle from burned rats. A factor or factors existed in plasma which increased both muscle and liver amino acid uptake postburn. PMID- 7880416 TI - Patterns of Staphylococcus aureus colonization, toxin production, immunity and illness in burned children. AB - Toxic shock syndrome toxin-one (TSST-1) produced from some but not all strains of Staphylococcus aureus is considered to be responsible for the development of the serious illness, toxic shock syndrome (TSS). The aim of this study was to establish the importance of S. aureus in the aetiology of suspected cases of TSS in acutely burned children. The pattern of colonization of S. aureus, and in particular toxic shock syndrome toxin-one (TSST-1) producing isolates, was studied in 53 burned children admitted as consecutive cases. S. aureus was not normally present on admission. Although it was the most common wound pathogen, it was acquired during the first few days after admission. Antibody status to TSST-1 on admission and at discharge was determined. Only half (49 per cent) of the children had antibodies to TSST-1. When it was possible to obtain paired admission and discharge samples in patients who had been given blood products, an assessment of seroconversion could be made. Two of the four patients given blood products during the resuscitation and postoperative period were antibody negative on admission (the other two were TSST-1 antibody positive). By discharge they had antibodies to TSST-1. Whilst the majority of donated blood products had antibodies to TSST-1 (76 per cent), some (24 per cent) did not. Seven of 53 children (13 per cent) developed a toxic shock-like illness which caused clinical concern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880417 TI - The prevalence of alcohol dependence in burned adult patients. AB - This study determined the prevalence of alcohol dependence in burned adult patients at the Tygerberg Hospital in Cape Town and describes patterns of alcohol consumption, socioeconomic adjustment and attitudes towards drinking. The subjects of the study were patients over the age of 18 years who were admitted consecutively to the Burns Unit between 21 March 1992 and 19 June 1992. Patients were screened for alcohol problems with the Michigan Alcoholism Screening Test. Thirty patients screened positively for alcohol dependence. A more comprehensive interview schedule was administered to these patients to obtain additional information. The incidence of alcohol dependence in the study group was high (57 per cent). Most patients indicated that they were regular weekend drinkers. More than half of the patients reported previous alcohol-related accidents and 57 per cent attributed their present injuries to alcohol intoxication. Ninety per cent of patients were motivated to change their drinking behaviour and 40 per cent were willing to accept some form of treatment. It was found that the burn injury represents a crisis during which treatment for alcohol problems can be introduced. The burn care team has a responsibility to address the patients' alcohol problems to prevent recurrent alcohol-related traumatic accidents. PMID- 7880418 TI - A new method of microskin mincing. AB - Microskin grafting has been used successfully for major burns when donor skin areas are inadequate to cover the skin defect. The microskin may be made by repeated cutting with scissors or by a specially designed machine. However microskin grafting is still not popular due to the difficulty of the mincing process, which may take hours to do. An easy and quick method of skin mincing using the Tanner-Vandeput Mesh Dermatome has been developed. The mincing process may be done in just a few minutes instead of hours. The skin pieces made with this technique are all of a uniform square shape and size (1.2 mm x 1.2 mm). Microskin grafting using the mincing technique has been carried out on 10 thighs of five patients with a fixed patch size (1.2 mm x 1.2 mm); an expansion ratio of 1:10 is used to ensure that the average interpatch distance would be within 5 mm for a better and quicker healing. All areas healed within 6 weeks without any secondary skin grafting. The resulting 'cobblestone' appearance of the healed skin is not good looking but there is no excess scar formation. The scar is soft and can be pinched up easily. This is an easy way of microskin mincing, it is quick and can be done in any clinic without specially trained personnel or the need to buy a new instrument. PMID- 7880420 TI - Psychiatric consultation and post-traumatic stress disorder in burned patients. AB - We report a prospective study of 65 burned inpatients referred for psychiatric consultation. All of the subjects in the sample were evaluated by a structured questionnaire and clinical interview. Reasons for referral were: suicide attempt by burning (n = 7), substance dependence (n = 8) and behaviour disturbed by coping difficulties (n = 50). The diagnoses were adjustment disorder (n = 40), alcohol dependence (n = 7), opiate dependence (n = 2), dementia (n = 3), depressive disorder (n = 5), schizophrenia (n = 1), delirium (n = 1) and post traumatic stress disorder (n = 5). Patients with post-traumatic stress disorder (PTSD) were specifically and carefully evaluated. There were no significant differences between patients with PTSD and adjustment disorder for severity and type of burn injuries. We conclude that PTSD is apt to be missed by the medical staff of burn units. PMID- 7880419 TI - Prognostic significance of early cardiac index measurements in severely burned patients. AB - Invasive monitoring during early resuscitation was performed. To compare the heamodynamic results of severely burned patients, the results of 38 patients hospitalized between 1988 and 1991 in the burn centre of Lyon were retrospectively reviewed. Survivors and non-Survivors' data were compared. No difference existed between the two groups in age, unit burn score, fluid requirement and dose of dobutamine. Survivors had a significantly higher cardiac index, O2 delivery and systolic blood pressure index than non-survivors. It is suggested that the ability to sustain a high cardiac index in response to the burn injury plays a role in the outcome of the patients. There is an indication that dobutamine could have a beneficial effect in this way. Further studies are needed to confirm the benefit of the maintenance of high cardiac index levels by the pressors. PMID- 7880421 TI - Self-inflicted burns. AB - Of 3371 patients admitted to the Vall D'Hebron Burns Center, Barcelona, between the years 1983 and 1991 inclusive, 67 patients had attempted self-inflicted burns (1.98 per cent). Over 75 per cent of these patients had previous psychiatric illness and 20 per cent had previously attempted suicide. The mean age was 38 years and the overall mortality rate was 30 per cent. Over 71 per cent were male patients. PMID- 7880422 TI - Use of cultured epidermal autografts in the treatment of large burns. AB - Mortality in patients with large areas of full skin thickness burns is, in part, due to complications developing during the period of prolonged delay required to obtain enough wound healing to permit skin grafting from limited donor sites. Cultured epithelial autograft (CEA) has become available as an alternative measure to the use of expanded skin autografts and regrafting. Small biopsies are taken and transported to the laboratories of BioSurface Technology where keratinocytes are grown to cover large areas during a 3-week period. The cultured keratinocytes are then available on petroleum jelly gauze which is applied to the patient. The gauze is used as a temporary dressing. To date, 37 patients have been biopsied. Grafts have been applied in 15. Graft 'take' averaged 71.5 per cent at our institution. Two of the patients grafted with CEA died of sepsis. One patient had a 100 per cent loss of the CEA grafts. In 12 patients, the use of CEA probably contributed significantly to wound coverage and survival. Such grafts are more susceptible to mechanical loss than routine autograft, although long term coverage after several years is considered to be satisfactory. The cost of the process is high. PMID- 7880423 TI - Early cardiorespiratory patterns in patients with major burns and pulmonary insufficiency. AB - We examined the case records of 50 consecutive patients with major cutaneous burns who required early mechanical ventilation. In 22 patients full haemodynamic and respiratory data were available within 24 h of their injury. Unexpectedly the haemodynamic and oxygen transport patterns of survivors and non-survivors were essentially similar although pulmonary artery occlusion pressure measurements and estimations of net fluid input suggest that non-survivors were relatively underresuscitated compared with survivors. Both groups showed inadequate oxygen utilization in the early stages of their injury despite normal (or above normal) levels of oxygen delivery. Invasive monitoring could possibly help this subgroup of burns patients. PMID- 7880424 TI - Reconstruction of postburn scar contracture of the neck by expanded skin flaps. AB - Flexion contracture of the neck after burns can produce severe functional deformity. Excision and split or full thickness skin grafts, local or distant flaps, and free flaps have been used for reconstruction. Recently, tissue expansion has been introduced as an additional reconstructive procedure. We have used tissue expansion for reconstruction of postburn neck contractures. Twelve patients with ages that ranged from 9 to 34 years were treated with expanded fasciocutaneous supraclavicular and shoulder flaps. No flap necrosis has been seen. In two patients, reconstracture occurred between the expanded flap and uninvolved skin. To date we have not seen any problems with nerve neuropraxia and impression on blood vessels. PMID- 7880425 TI - Burns from a dust explosion. AB - Two cases of burn injury following a dust explosion are presented. It is important to (1) rule out other serious injuries and (2) continuously reassess the patient for respiratory injury. The mechanism of dust explosions is described and preventative measures are discussed. PMID- 7880426 TI - Severe electric burn of the skull. AB - We report a case of severe injury of the scalp and skull caused by high tension electric current. The patient developed tetraplegia. The surgical steps undertaken are also described. We used two consecutive free flaps which failed 5 days after each operation. We discuss the possible causes for flap failure, which we think was due to damaged receptor vessels. The wound was closed after expanding the adjacent scalp. Scalp expansion was an uneventful procedure, however infection of the cavity developed. We overcame this problem by an aggressive approach (cavity irrigation, daily expansion and systemic antibiotherapy). The use of a synthetic mesh to avoid cerebral herniation through the bone defect is also described. PMID- 7880427 TI - Immediate reconstruction of chest and abdominal wall defect following high voltage electrical injury. AB - The report describes a postelectrical burn lateral chest wall and ipsilateral upper abdominal wall defect, successfully managed by immediate adequate debridement and use of a latissimus dorsi myocutaneous flap. PMID- 7880429 TI - Recent references. PMID- 7880428 TI - Corneal burns with eyelid sparing and their treatment. AB - In a flash injury the eyes are protected by the blink reflex. With our patients the eyes were open looking for a means of escape, exposing the globe to injury by hot smoke and protecting the eyelids. It is essential to examine the eyes in any facial burn, especially if there is any history of being injured in an enclosed space. If there are any signs of corneal injuries then the assistance of an ophthalmologist should be sought. PMID- 7880430 TI - Screening of fetal stem cells for infection and cytogenetic abnormalities. AB - Fetal stem cell transplantation may rely on material from therapeutic abortions. It is essential that the stem cell transplant does not transmit any microorganisms that may affect the fetus and that genetically abnormal cells are avoided. To evaluate such contamination, human fetal stem cells collected February 1992 - December 1993 were analyzed for bacterial and fungal growth, and the placentas were karyotyped. Four samples of 70 were positive for different pathogens. Serological screening of 43 women during this period resulted in five seroconversions and revealed one carrier of anti-HCV. Karyotyping revealed two abnormal findings out of 72 samples. Thus, the concept of using material from therapeutic abortions is safe. PMID- 7880431 TI - Clinical significance of low levels of second-trimester maternal serum human chorionic gonadotropin. AB - OBJECTIVE: To determine if unexplained low second-trimester maternal serum human chorionic gonadotropin (MShCG) is a useful predictor of complications of pregnancy. STUDY DESIGN: Between 2/1/90 and 1/3/91, 3,116 patients underwent prenatal screening using second-trimester maternal serum alpha-fetoprotein (MSAFP), MShCG and maternal serum unconjugated estriol (MSuE3). Among these, there were 160 patients with complete obstetrical history who had second trimester MShCG < 0.4 multiples of the median (MoM). These were compared to 261 controls with complete obstetrical history and a normal second-trimester MSAFP, MSuE3 and MShCG. RESULTS: No differences were found in gestational age at delivery, neonatal weight, premature rupture of membranes or pregnancy loss. The relative risk of pregnancy-induced hypertension in the study group was 0.29 (p < 0.01) and that of gestational diabetes was 0.3 (p < 0.05). Only when low MShCG was associated with a high or low MSAFP or low MSuE3 was there a significantly increased loss of pregnancy (relative risk 11.7; p < 0.0001). CONCLUSION: The data suggest that second-trimester MShCG < 0.4 MoM by itself has no influence on the outcome of pregnancy. PMID- 7880432 TI - Fluorescent in situ hybridization and second-trimester sonographic anomalies: uses and limitations. AB - The critical need for rapid and reliable karyotype analysis can be no greater than in the setting of sonographic fetal anomalies. Fluorescent in situ hybridization (FISH) directly applied to interphase chromosomes can decrease the time required to identify the common aneuploidies. Our retrospective study reviewed 50 consecutive patients with sonographic fetal anomalies who underwent FISH. Within this high risk group, nonmosaic chromosomal aneuploidies were present in 16% of the fetuses (8 of 50), and 2 additional fetuses had cytogenetic abnormalities: 1 case, 46,XY,-12,+der(12)t(12;13)(p13; q14.1), and 1 case a 10% mosaic for trisomy 21. Of the 10 cytogenetically abnormal fetuses, FISH was able to identify correctly all 8 of the nonmosaic aneuploidies within 2 days of receipt of the specimen in the laboratory. Clinical decisions can be made on the basis of concordant FISH and ultrasound abnormalities, shortening the decision making process for most of the aneuploid cases. However, our experience demonstrates some of the limitations of current FISH protocols and the continued necessity for formal karyotype analysis. PMID- 7880433 TI - Maternal peripheral blood lymphocyte subpopulations in normal and pathological pregnancies. AB - Flow cytometry was used to determine lymphocyte subpopulations in maternal blood from 143 pathological pregnancies: 50 with fetal aneuploidy; 32 with missed abortions; 12 with ectopic pregnancies; 20 with multi-fetal pregnancies, and 29 with pregnancies complicated by intrauterine growth retardation (IUGR). The values were compared to those of 240 women with normal singleton pregnancies at 8 40 weeks of gestation and 20 non-pregnant controls. In early pregnancy (8-10 weeks), compared to non-pregnant values, there was a decrease in the percentage of CD4+ cells and CD4+ to CD8+ ratio and an increase in the percentage of CD8+ cells. In later pregnancy, the CD4+ cell percentage and CD4+ to CD8+ ratio increased and the CD8+ cell percentage decreased to reach non-pregnant values at term. The percentage of natural killer (CD3- and CD16/56+) cells decreased with gestation, while the percentage of B (CD19+) cells did not change significantly. In IUGR, the percentage of CD4+ cells and CD4+ to CD8+ ratio were decreased, while the percentage of CD8+ cells was increased. In contrast, in the groups of missed abortions and ectopic pregnancies, the CD4+ to CD8+ ratio was increased. In multifetal pregnancies and those with fetal aneuploidies there were no significant differences in maternal lymphocyte subpopulations from normals. PMID- 7880434 TI - Prenatal diagnosis of Duchenne muscular dystrophy by polymerase chain reaction analysis. AB - The efficacy of the polymerase chain reaction (PCR) in the first-trimester prenatal diagnosis of Duchenne muscular dystrophy (DMD) was examined. Twenty seven fetuses from 26 Japanese pedigrees at risk for DMD were analyzed. PCR restriction fragment length polymorphism analysis, multiplex PCR, and dinucleotide repeat polymorphism analysis were used. Of 16 males, 11 were determined to be unaffected, 4 were affected, and the remaining 1 was undetermined. Of the 11 female fetuses, 1 was diagnosed as a noncarrier, 4 were carriers, and the carrier status of the remaining 6 was not determined at the option of the patients, although DNA polymorphisms could be detected in those patients. Prenatal diagnosis by PCR analysis was possible in 96% of the fetuses tested (26 of 27). PMID- 7880435 TI - Diagnostic use of cordocentesis in twin pregnancy. AB - We performed percutaneous umbilical blood sampling, under ultrasound guidance, in both twins of 11 twin pregnancies in whom twin-to-twin transfusion syndrome was suspected. Chorionicity and the presence of placental vascular anastomoses were assessed postnatally. The hemoglobin concentration, hematocrit and other biochemical variables in fetal blood were evaluated in both twins. The mean hemoglobin difference between the large and small twins was 4.8 g/dl (range 1.8 8.1 g/dl) in 5 monochorionic discordant twin pairs, and 1.2 g/dl in a monochorionic twin pair without discordancy. Hemoglobin values did not differ between dichorionic twins. The mean hematocrit difference between monochorionic discordant twins was 18.3%. In dichorionic discordant twins, the inter-twin hematocrit difference was very small. Total protein and albumin were normal in all twins. PMID- 7880436 TI - Endovaginal sonographic diagnosis of craniorachischisis at 13 weeks of gestation. AB - A rare case of craniorachischisis associated with trisomy 18 is described. The diagnosis was made by endovaginal sonography during the first trimester of pregnancy. The case is interesting for two reasons. First, it confirms the importance of carrying out an accurate sonographic examination during the first trimester. Second, it shows us that the postmortem examination should be performed by an experienced anatomist: embryos need to be embedded in paraffin wax for microscopic observation and, at present, little is known about the abnormalities of embryo anatomy. PMID- 7880437 TI - Four cases of absent ductus venosus: three in combination with severe hydrops fetalis. AB - Ductus venosus links the umbilical vein and the portal vein to the inferior vena cava. It is of great significance for the developing fetus but of minor importance to the growing infant where it normally obliterates and is transformed to the ligamentum venosum. An absent ductus venosus implies that the oxygenated blood from the umbilical vein has to circulate through the liver. We report 4 cases with this malformation. Prenatally, three fetuses had an extreme hydrops, especially hydrothorax. In two fetuses hydrops was severe already in the second trimester of pregnancy. Termination was performed. In the third case, hydrops was first diagnosed in the 36th week of gestation. The fourth case had an ultrasound examination in the 34th week of gestation. There was no hydrops but a disproportion with a very small head and abdominal diameter compared to femur length. Postpartum both these infants died. At autopsy, the only structural malformation in the three hydrops cases was an absent ductus venosus. In the fourth case there were other anomalies. PMID- 7880438 TI - Fetal intervention for congenital diaphragmatic hernia. AB - Despite improvements in surgical techniques, the results of open fetal surgery to correct congenital diaphragmatic hernia have been disappointing. Hysterotomy induces preterm labour and, where there is a large volume of liver in the fetal chest, reduction of the liver into the abdomen induces immediate fetal death. Less invasive techniques, using both open surgery and fetoscopy, are being developed in the hope of reducing fetal demise. These techniques include blocking the trachea, the creation of an artificial gastroschisis and induction of graft tolerance for postnatal lung transplantation. PMID- 7880439 TI - Cloning of mouse RP-8 cDNA and its expression during apoptosis of lymphoid and myeloid cells. AB - A partial-length cDNA encoding a cell death-associated gene designated RP-8 was cloned from rat thymocytes by Owens and co-workers (Mol. Cell. Biol. 11, 4177 4188, 1991). They reported that transcription of RP-8 was induced when rat thymocytes were caused to undergo apoptosis triggered by either radiation or treatment with dexamethasone. To study the role of RP-8 in cell death in the mouse, we have cloned a full-length mouse RP-8 cDNA from a mouse thymus cDNA library. The mouse RP-8 gene encodes of protein of 343 amino acids with 92% amino acid identity to the rat RP-8 protein. Expression of mouse RP-8 was not altered in a factor-dependent myeloid line induced to undergo apoptosis by growth factor withdrawal, or when a lymphoid cell line was triggered to undergo apoptosis by irradiation. Although these data do not prove that RP-8 is not a cell death gene, they show that RP-8 expression is not sufficient for apoptosis, and that transcriptional up regulation of RP-8 is not universally associated with apoptosis. PMID- 7880440 TI - Rat growth hormone receptor/growth hormone-binding protein mRNAs with divergent 5'-untranslated regions are expressed in a tissue-specific manner. AB - In the rat, the growth hormone receptor (GH-R) gene generates two transcripts, one encoding the transmembrane GH-R, and a shorter one encoding the GH-binding protein (GH-BP). These transcripts exhibit a high degree of heterogeneity in their 5'-untranslated regions (5'-UTRs). Some of the exons encoding these 5'-UTR variants may be flanked by distinct promoter regions whose activity would result in the tissue-specific expression of the GH-R gene. To assess this possibility, we used single-sided polymerase chain reaction (PCR) amplification to characterize 5'-UTR variants in rat GH-R cDNAs, and by using 5'-UTR-specific probes, we determined their pattern of expression in several tissues. Besides two previously described variants (V1 and V2), three new 5'-UTR variants were identified, extending 56 nucleotides (V3), 135 nucleotides (V4), and 209 nucleotides (V5) upstream of the ATG translation initiation codon. The expression of GH-R and GH-BP transcripts was clearly tissue specific. In the liver, GH-BP mRNA was the predominant transcript, whereas in other tissues, there was equivalent expression of both transcripts or predominant expression of GH-R mRNA. With respect to the tissue distribution of the 5'-UTR variants in particular, variants V1 and V5 exhibited a pattern of expression closely resembling that seen with an exon 2 probe, with the overall expression of variant V1 being much higher than that of variant V5. The V2 species was exclusively expressed in liver. Variant V3 was expressed at low levels in liver, muscle, heart, and kidney; in muscle and heart, it was preferentially associated with GH-BP transcripts. Variant V4, although present in liver, was more abundant in extrahepatic tissues and predominantly found in GH-R mRNA transcripts. Southern blot analyses were consistent with exon 2 and the exons encoding the V1 and V2 sequences being in proximity, with the other 5'-UTR sequences being encoded by exons located further upstream of exon 2. These findings support the concept that different 5'-UTR variants are the result of the different promoters acting in a tissue-specific manner. The association of specific 5'-UTR variants with either GH-R or GH-BP transcripts raises the possibility that the alternative splicing process that generates GH-BP mRNA in the rat might be controlled by the 5'-flanking region regulating the expression of specific leader exons. PMID- 7880441 TI - Identification of an internal promoter of the latent membrane protein 1 gene of Epstein-Barr virus. AB - The latent membrane protein 1 (LMP 1) gene of an Epstein-Barr virus (EBV) variant derived from an nasopharyngeal carcinoma (NPC) biopsy in Taiwan was isolated and characterized (Chen et al., 1992). Transient expression of the genomic sequence containing this gene showed two proteins with molecular masses of 62 kD and 50 kD, respectively, recognized by LMP-specific antibody S12. To determine if these two proteins were derived from independent promoters, we generated a series of mutant plasmids from plasmid pT7(E) that contained the upstream and the coding regions of the LMP 1 gene. These mutants were introduced into a human epithelial cell line, C33A, and LMP 1 proteins were examined by Western blotting analysis with the S12 antibody. Data showed that plasmid with a fragment containing approximately 3 kb of upstream sequence of LMP 1 gene produced the 62-kD protein. Removal of 2.7 kb of the upstream sequence (plasmid delta 2710, deleted to nucleotide 169,571) resulted in the production of both 62-kD and 50-kD proteins. This suggested that the upstream sequence interfered with the production of the 50-kD protein. Plasmid DNA deleted to Acc I site (nucleotide 169,223) generated only the 50-kD protein, designated as tr-LMP. Further deletion to nucleotide 169,038 resulted in the expression of another smaller LMP1 (49 kD, named as str LMP1). The region between nucleotides 168,789 and 169,038 was tested to see if it possessed a promoter activity by using the luciferase gene as a reporter. Data showed that this region contained promoter activity with a level compatible to the previously reported ED-L1A promoter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880442 TI - Autoregulation of cloned human protein kinase C beta and gamma gene promoters in U937 cells. AB - Protein kinase C (PKC) serine/threonine kinases transduce cellular signals initiated by phospholipase C activation and diacylglycerol production. Human gene sequences from the beta and gamma isoforms were cloned and sequenced, and transcriptional regulation was studied. The major PKC beta transcription initiation site was identified by primer extension and S1 nuclease protection. Additional transcription initiation sites were located within a CpG-rich region proximal to the ATG. The transcription initiation site of the PKC gamma gene was identified by primed cDNA synthesis. In transfection experiments, the PKC gamma promoter was expressed at high level in U937 and HL60 cells but not in COS-1 cells. A sequence motif (AnAGATTCanAGAGnCa), reiterated over at least 1 kb, was located approximately 1.5 kb 5' of the PKC gamma translation initiation codon. This repetitive motif is abundant in run-on RNA in the hematopoietic and epithelial cell lines tested. Analysis of promoter deletion constructs by transient transcription assays in U937, IM9, and COS-1 cells showed negative regulation of the PKC beta promoter by sequences located between -3,000 and -690. although no homology between PKC beta and PKC-gamma 5'-flanking sequences was observed, both PKC beta and PKC gamma promoters were potently induced by 12 phorbol 13-myristate in transfected U937 cells. PMID- 7880443 TI - The Dfur2 gene of Drosophila melanogaster: genetic organization, expression during embryogenesis, and pro-protein processing activity of its translational product Dfurin2. AB - The gene structure and expression of the Dfur2 gene of Drosophila melanogaster, which encodes the subtilisin-like serine endoprotease Dfurin2, was studied. The Dfur2 gene is very compact in contrast to the related Dfur1 gene, which has an estimated size of over 100 kbp. The 6-kb Dfur2 mRNA is encoded by 16 exons dispersed over a genomic region of about 9 kbp. The exon/intron organization shows conservation of intron positions not only in comparison with Dfur1, but also with the related mammalian genes FUR, PC1/PC3, PC2, and PC4. This conservation supports the hypothesis that all genes belonging to the family of subtilisin-like pro-protein processing enzymes are evolutionary related by descent from a common ancestral gene. In primer extension experiments, Dfur2 transcription initiation sites were identified in the presumed Dfur2 promoter region. This region was found to contain general RNA polymerase II promoter elements like a potential TATA box, a potential CAP signal, and several potential CCAAT boxes. Also, several sequence motifs putatively corresponding to binding sites for Drosophila transcription factors like zeste, bicoid, and engrailed were found to be present. RNA in situ hybridization experiments on Drosophila embryos revealed presumably maternal Dfur2 expression until the syncytial blastoderm (stage 5 of embryogenesis), no expression during gastrulation (stage 9), transient expression in a subset of neurons in the central nervous system of stage 12-13 embryos, and, from stage 13 onwards, expression in the developing tracheal tree. In a vaccinia expression system, the endoprotease Dfurin2 not only cleaved wild-type precursor of von Willebrand factor (pro-vWF) with pro-region cleavage site R-S-K-R decreases, but also, although to a lesser extent, pro-vWF mutants in which the P2 (vWFK-2A) or P4 (vWFR-4A) basic residue with respect to the pro-region cleavage site had been mutated. This cleavage specificity resembles that of human furin. The cleavage of pro-vWF by Dfurin2 shows that the previously reported lack of cleavage of the precursor of the beta A-chain of activin-A by Dfurin2 in this vaccinia expression system is substrate determined. PMID- 7880444 TI - Sequence and expression of bone morphogenetic protein 3 mRNA in prolonged cultures of fetal rat calvarial osteoblasts and in rat prostate adenocarcinoma PA III cells. AB - We have examined expression of bone morphogenetic protein 3 (BMP-3) mRNA in normal rat osteoblasts in culture as they undergo differentiation to form bone like structures, and have found that expression of BMP-3 mRNA in primary fetal rat calvarial (FRC) cells is discontinuous and shows at least four different sized transcripts. BMP-3 mRNA expression has a distinct temporal pattern during bone cell differentiation of FRC osteoblasts. Previously, we showed that BMP-3 mRNA is expressed in normal and neoplastic rat and human prostate tissues, and in human osteosarcoma cells, as multiple transcripts. To compare the nature of these transcripts in different tissues, three cDNA clones encoding BMP-3 have been isolated by reverse transcription-polymerase chain reaction (RT-PCR) and cDNA library screening from human prostate cancer PC-3 cells, rat prostate adenocarcinoma PA III cells, and primary FRC cells. Analysis of these clones has revealed that the nucleotide sequence of BMP-3 found in human prostate cells is identical to that found in human bone cells. The rat BMP-3 sequences from bone and prostate cells are also identical but show a high degree of variation in the pro- or precursor region compared with human BMP-3. The biological significance of these differences in these two species is unknown. PMID- 7880445 TI - Cloning and characterization of two forms of bovine polymeric immunoglobulin receptor cDNA. AB - The polymeric immunoglobulin receptor (transmembrane secretory component) mediates transcellular transport of dimeric immunoglobulin A (IgA) and pentameric IgM in glandular and mucosal epithelial cells. cDNAs encoding two forms of the bovine polymeric immunoglobulin receptor (pIgR) have been cloned and sequenced. The long form contains 3,527 bp and predicts a single open reading frame of 2,271 bp encoding a protein of 757 bp. The extracellular part contains five immunoglobulin (Ig)-like domains. The shorter form lacks the region from residues 458-1,111 corresponding to Ig-like domains 2 and 3. In Northern blot analysis of various bovine tissues, only the long form of pIgR mRNA was detected. By using the reverse transcription-polymerase chain reaction (RT-PCR), both forms were detected. An alignment of the cytoplasmic tail of the pIgR from bovine, human, rabbit, and rat revealed highly conserved areas that may reflect the importance of these regions for intracellular sorting of the receptor. PMID- 7880446 TI - Characterization of the proximal promoter of the human histone H2A.Z gene. AB - Histone H2A.Z is a distinct and evolutionarily conserved member of the histone H2A family whose synthesis, in contrast to that of most other histone species, is not dependent on DNA replication. The gene for H2A.Z lacks the signals involved in the 3' processing of replication-linked histone mRNA species and contains introns as well as polyadenylation signals. The H2A.Z gene proximal promoter, a 200-bp region upstream of the transcription start site that provides maximal activity in CAT reporter studies, contains three CCAAT and two GGGCGG elements as well as a consensus TATA element. In vitro DNase I footprint analysis of this region indicated that the central CCAAT and the distal GGGCGG elements were protected by factors present in HeLa nuclear extract. Site-directed mutations of selected promoter elements were generated in the H2A.Z gene promoter region of a CAT reporter construct by a novel one-step PCR procedure. Of the elements examined, the central CCAAT element was found to be the most important determinant of promoter activity; its disruption decreased CAT reporter activity by 65%. Disruption of the proximal CCAAT or the distal GGGCGG elements led to decreases in activity of 40%, while disruption of any of the other examined led to smaller decreases. Gel-mobility shift analysis showed that the three CCAAT elements had overlapping but not identical binding specificities for nuclear factors. The two GGGCGG elements both were found to bind transcription factor Sp1, but the distal element bound Sp1 with higher affinity. The findings show that the central and proximal CCAAT elements and the distal GGGCGG element appear to be the major determinants of the transcriptional activity of the H2A.Z gene. PMID- 7880447 TI - Cognitive deficits induced by global cerebral ischaemia: relationship to brain damage and reversal by transplants. AB - The CA1 and hilar fields of the hippocampus are highly vulnerable to lack of oxygen after interruption of blood flow to the brain. Severe anterograde memory loss, seen in a significant proportion of heart attack survivors, has been attributed to selective bilateral ischaemic damage to the hippocampus. Animal models of global ischaemia, induced by extracranial occlusion of the major ascending arteries, enable assessment of the neuropathological and functional consequences of transient interruption of cerebral blood flow, and can inform strategies to reduce or alleviate ischaemic brain damage. This review focuses firstly on the nature of cognitive deficits induced by global ischaemia, how far they are consistent with lesion-based accounts of hippocampal function, and the extent to which these deficits can be correlated with CA1 cell loss. The second focus of the review is to examine the limited evidence for graft-induced recovery of cognitive function in animals subjected to global ischaemia. Recent findings that grafted foetal cells from discrete hippocampal fields follow appropriate laminar routes to form functional connections with host neurons, and that growth factors protect cells from ischaemic damage, have suggested that CA1 or trophic grafts placed in the region of ischaemic CA1 cell loss might restore or protect this vulnerable sector, and reduce cognitive deficits. PMID- 7880448 TI - Behavioral impairment in radial-arm maze learning and acetylcholine content of the hippocampus and cerebral cortex in aged mice. AB - Age-related changes in spatial learning performance were studied in relation to acetylcholine (ACh) content of brain regions in male aged (28-month-old) and young (5-month-old) mice of BDF1 strain. As there were large individual differences in the spatial performance of aged mice, the aged mice were divided into two subgroups, old A and old B. The old A group included the six best performers out of the 12 aged mice and the old B group included the remaining 6 worst performers. In a radial-arm maze task with 8 baited arms, aged mice in the old B group showed a marked deficit in acquisition performance and habituation to the apparatus. In the more difficult maze task with only 4 baited arms, the aged mice in the old B group exhibited marked impairment both in working memory and reference memory throughout training, whereas the aged mice in the old A group showed deficits in reference memory during the first 20 days of training and working memory during the last 20 days relative to young mice. Neurochemical analysis revealed significant decreases in the ACh content of the hippocampus and striatum in both aged groups, and in the frontal cortex and posterior cortex of the old B group as compared to the young group. Correlational analysis showed significant correlations between learning performance in the spatial task and ACh levels in the hippocampus, frontal cortex, and posterior cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880449 TI - Low-dose X-ray-induced depression of sexual behavior in mice. AB - In recent years concern over the biological stimulatory-effect of low-dose noxiousness has been growing. In the course of a study of low dose X-rays effects, we found that male ICR white Swiss mice showed remarkable suppression of mounting behavior after whole body irradiation by 5 to 15 cGy X-rays. Higher doses (25-35 cGy), however, did not induce such effects. Irradiation of the mice head-portion produced these effects, suggesting the important role played by the brain in this phenomenon. Furthermore, we examined the difference between the presence and absence of psychological stress when the mice were exposed to radiation. The results showed that the depression of mounting behavior could be observed in stressed mice, which were housed in prolonged social-isolation, but not in non-stressed mice, that were allowed to socialize. The central nervous system of adult animals is usually considered to be extremely radioresistant. However, the results presented here clearly demonstrate that the brain is one of the most radiosensitive organs in terms of physiological changes. PMID- 7880450 TI - The inhibitory effect of norharman on morphine withdrawal syndrome in rats: comparison with ibogaine. AB - Norharman (20 mg/kg, i.p.) and ibogaine (40 mg/kg, i.p.) significantly attenuated naloxone (4 mg/kg, i.p.)-precipitated withdrawal syndrome in morphine-dependent rats. Several withdrawal signs, such as teeth-chattering, chewing, penile licking and diarrhoea, were decreased by both norharman and ibogaine. In addition, norharman reduced also the withdrawal grooming and rearing. It is concluded that both norharman and ibogaine are inhibitors of withdrawal syndrome in morphine dependent rats. PMID- 7880451 TI - Disorders of visuo-spatial attention in patients with unilateral brain damage. AB - Visuo-spatial inattention (VSI) was examined in 390 patients with ischemic insult to the right or left cerebral hemispheres. VSI was revealed in 44 out of 80 patients with right parietal lobe damage and in 30 out of 70 subjects with right occipital lobe injury. Only one patient out of 100 with left hemisphere injury has shown the signs of VSI. These data confirm the suggestion that the right parietal and occipital regions are crucial for visuo-spatial attention, whereas the left hemisphere is of minor import. PMID- 7880452 TI - Differential influence of corticosterone and dexamethasone on schedule-induced polydipsia in adrenalectomized rats. AB - Previous studies have shown that adrenalectomy prevents the normal acquisition of schedule-induced polydipsia (SIP), while corticosterone (CORT) administration reinstates this behavior in adrenalectomized (ADX) rats. These studies investigated which corticosteroid receptor is responsible for mediating CORT effects on SIP. In Experiment I the effects of dexamethasone (DEX) and CORT on the acquisition of SIP were studied. DEX and CORT pellets (respectively 15 mg and 200 mg) were implanted subcutaneously in ADX rats. CORT but not DEX replacement was able to reinstate SIP in ADX rats. Because DEX binds almost exclusively to glucocorticoid receptors (GRs), while CORT binds to both GRs and mineralocorticoid receptors (MRs), results from Experiment I indicated that occupancy of GRs alone is not sufficient for SIP acquisition. In Experiment II CORT pellets of different concentrations (1, 10, 50, 200 mg) were implanted in ADX rats in order to determine whether MRs alone, or a combination of GRs and MRs are required for SIP reinstatement. Results from Experiment II showed that the 1 and 10 mg CORT pellets were not able to reinstate SIP in adrenalectomized rats, while animals implanted with 50 or 200 mg pellets did exhibit the behavior. These results indicate that occupancy of both MRs and GRs is required for SIP acquisition. PMID- 7880453 TI - Rotational swimming tendencies in the dolphin (Tursiops truncatus). AB - Anecdotal evidence suggests that dolphins placed in a pool exhibit stereotypic swimming in circles. The present study confirmed these observations in a sample of thirteen dolphins. The majority of dolphins (84.6%) showed highly consistent directional swimming in counterclockwise circles. The latter directionality held throughout the circadian cycle and resisted environmental manipulations. Only social interaction was capable of altering the directionality of circumnavigation. The consistency of unidirectional swimming is considered paradoxical in view of the existing evidence regarding the alternating of hemispheric activity in sleeping dolphins. PMID- 7880454 TI - Effect of environmental stressors on time course, variability and form of self grooming in the rat: handling, social contact, defeat, novelty, restraint and fur moistening. AB - Grooming is often related to dearousal following stressors. Interestingly, electrical and chemical stimulation of the paraventricular nucleus of the hypothalamus (PVH), at levels that are known to activate the hypothalamus pituitary adrenal axis (HPA), also elicits grooming. At the level of the PVH, the neuroendocrine stress response is apparently still linked to the behavioural response to stressors. However the precise nature of this relation is not fully understood. Here we report on grooming in rats following exposure to different stressors which are known to activate the HPA axis. Stressors such as handling, restraint, novelty, encounters with aggressive or non-aggressive conspecifics, or moistening the fur, change the amount and time course of grooming upon return in the home cage, as compared with controls that are just handled. However, the amount of grooming is not directly related to the strength of the stressor. Defeated intruders groom less upon return in their home cage. Novelty and non aggressive encounters with conspecifics reduce the variation in the amount of grooming between rats. The time course of grooming over the 20-min observation period also differs between treatments. Following restraint, or exposure to non aggressive conspecifics, grooming first increases and then decreases. Moistened rats immediately start grooming which subsequently decreases. Rats used as intruders in the territory of another rat maintain a constant low level of grooming. Rats placed in a novel cage steadily increase grooming during the 20 min observation period. These results suggest that grooming cannot be simply understood as an immediate response necessary to reduce arousal following stressors. Following exposure to a stressor, grooming rather seems temporary suppressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880455 TI - Prefrontal cortex and the relative associability of taste and place cues in rats. AB - The effects of cutting the corticocortical connections between medial and sulcal prefrontal areas on the conditioning of taste and place cues were examined. In Experiment 1, rats were simultaneously exposed to taste and place cues before injection of 0.15 M LiCl. In controls, a significant conditioned taste aversion (CTA) but no conditioned place aversion (CPA) was observed. In contrast, rats with bilateral knife cuts showed a significant CPA but a weaker CTA. To test whether these results could have been due to the effects of simultaneously exposing the rats to taste and place cues during conditioning, rats were trained independently in either CTA or CPA paradigms in Experiment 2. In the CTA test, rats both in operated and control groups showed a CTA when first tested. Rats with bilateral knife cuts, however, showed a weaker CTA than those in the control group. In the CPA test, rats in the control group did not exhibit a CPA, whereas the knife cut group did. Rats with sham lesions tested in Experiment 2 did not differ from control subjects on either the CPA or the CTA test. Thus, bilateral cuts increased the CPA and decreased the CTA even when tested independently. These results indicate that the relative ease of association of place and taste stimuli may be accounted for in part by the organization of the intrinsic connections of the prefrontal cortex in the rat. PMID- 7880456 TI - Autoradiographic distribution of neurotransmitter and second messenger system receptors in animal brains. AB - We investigated species difference in binding of major neurotransmitters and intracellular second messengers in the gerbil brain and the rat brain using receptor autoradiography. [3H]Phorbol 12,13-dibutyrate (PDBu), [3H]inositol 1,4,5 trisphosphate (IP3), [3H]PN200-110, [3H]muscimol, [3H]MK-801, [3H]cyclohexyladenosine (CHA),and [3H]quinuclidinyl benzilate (QNB) were used to label protein kinase C, IP3 receptor, L-type calcium channel, gamma-aminobutyric acidA (GABAA) receptor, N-methyl-D-aspartate (NMDA) receptor, adenosine A1 receptor, and muscarinic cholinergic receptor, respectively. Autoradiographic distributions of the bindings of most neurotransmitters and second messengers were particularly found in the limbic system and basal ganglia in both gerbil and rat brains. However, marked differences in these bindings between the gerbil brain and the rat brain were also recognized in the above regions. In particular, among 7 ligands used, the gerbil had high [3H]PDBu and [3H]CHA binding sites throughout the brain compared to those in the rat brain except for a few areas. By contrast, the rat exhibited high [3H]MK-801 binding sites in various brain regions, as compared with the gerbil brain. Thus, the gerbil differ from the rat with respect to the binding sites of major second messengers and neurotransmitters in the brain. The results may help better elucidate the relationship or species difference between gerbils and rats for neuronal function and behavioral pharmacology. PMID- 7880457 TI - Behavioral effects of phencyclidine and its major metabolite, (trans)4-phenyl-4 (1-piperidinyl)cyclohexanol, in mice. AB - To elucidate the biological activity of natural metabolites of phencyclidine (PCP), we examined the behavioral effects of a major metabolite, the trans isomer of 4-phenyl-4-(1-piperidinyl)cyclohexanol [(trans)PPC], in mice, (Trans)PPC caused dose-related increase in locomotor activity and rearing in mice when injected intraperitoneally at the doses ranging from 10 to 30 mg/kg. (Trans)PPC at any dose tested failed to produce swaying and falling. On the other hand, PCP at the doses ranging from 1 to 10 mg/kg caused swaying and falling as well as hyperlocomotion in a dose-related manner. These indicate that unlike PCP, hyperlocomotion and rearing may be the predominant behavioral responses to (trans)PPC in the 10-30 mg/kg dose range. Furthermore, it is feasible to surmise that not only PCP but also its major metabolite (trans)PPC is involved in psychotic reactions produced by PCP. PMID- 7880458 TI - Phase specific morphological changes induced by social experience in two forebrain areas of the zebra finch. AB - We examined the changes of spine density in Golgi preparations of two different areas of the forebrain of the zebra finch, the ANC (Archi-Neostriatum caudale) and MNH (medial Neo-Hyperstriatum) during development, after transferring male birds from isolation to a social condition (exposure to a female for 1 week), and after a second isolation period. MNH and ANC are two of four brain regions which are strongly activated if a male bird is exposed to a female after some time of isolation. The results of our study can be summarized as follows. 1: a peak decline trend is observed in ANC, but not in MNH. 2: rearing conditions do not affect the development of both areas until day 70. 3: from 80 days of age, isolation leads to reduced spine density within ANC, but to enhanced spine density within MNH. 4: short social contact after isolation diminishes or eliminates the effects of isolation by an enhancement of spine density in ANC and a reduction of spine density within MNH. 5: the effects of short social rearing after isolation are reversible within ANC, but not within MNH. We presume that the alterations of spine density, which are induced by changes in social conditions, are restricted to ages older than 70 days by hormonal factors. We propose that the complexity of the ANC neuronal net follows the complexity of the social environment, and that the level of arousal is the most important factor influencing the complexity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880459 TI - Lack of effect of lesions in the anterior cingulate cortex and retrosplenial cortex on certain tests of spatial memory in the rat. AB - The effects of cytotoxic lesions in either the anterior cingulate cortex or the retrosplenial cortex were compared with those of fornix lesions on three tests of spatial memory. Two of the tasks, delayed nonmatching-to-position and spatial reversal learning, were tested in an automated apparatus. The third task, forced alternation, was tested in a T-maze. Neither anterior cingulate nor retrosplenial cortex damage produced any significant impairment on the three tasks. In contrast, rats with fornix lesions (hippocampal system damage) were markedly impaired on all three tasks. The results, which were considered in the light of proposals for a hippocampal--anterior thalamic--cingulate system that is important for spatial memory, suggest that neither of the cingulate regions involved in this study form a critical subcomponent of this proposed system. It is therefore assumed that the cingulate cortices are only critical for certain classes of spatial problem. It is also suggested that in some previous studies the effects of inadvertent damage to the cingulum bundle may have contributed to the apparent effects of cingulate lesions. PMID- 7880460 TI - Caries inhibition by fluoride-releasing primers. AB - This study evaluated the caries inhibition of dentin primers with the addition of fluoride. Two standardized Class V preparations were placed in 20 molars, the gingival margin placed below the cementoenamel junction and the occlusal margin placed in enamel. Two dentin primers (Syntac and ScotchPrep) were placed in equal numbers of 20 preparations, according to manufacturer's instructions. Ammonium fluoride (10% by weight) was then added to these primers and they were placed in the remaining 20 preparations, opposing the non-fluoridated primer of the same system. All teeth were then restored with a non-fluoridated resin composite. All teeth were subjected to an artificial caries challenge (pH 4.2) for 5 days. Sections of 100 microns were obtained, photographed under polarized light microscopy, then demineralized areas were quantitated by digitization. Results demonstrated the mean areas (mm2 +/- S.D.) demineralization at 0.25 mm, 0.5 mm and 1.0 mm from the restoration margin to be: Syntac/fluoride (1.44 +/- 0.49, 1.68 +/- 0.54, 3.72 +/- 0.74); Syntac (1.99 +/- 0.58, 1.50 +/- 0.35, 2.98 +/- 1.26); ScotchPrep/fluoride (1.23 +/- 0.68, 1.55 +/- 0.64, 3.08 +/- 1.16); ScotchPrep (1.90 +/- 0.83, 1.71 +/- .038, 3.36 +/- 0.62). A paired t-test indicated primers with fluoride to demonstrate significantly less demineralization 0.25 mm from the restoration margin (P < 0.07). PMID- 7880461 TI - Reduction of viable bacteria in dental aerosols by preprocedural rinsing with an antiseptic mouthrinse. AB - Two double-blind controlled clinical studies were conducted to determine the efficacy of preprocedural rinsing with Cool Mint Listerine Antiseptic mouthrinse on the level of viable bacteria recovered from dental aerosols when generated immediately after and 40 minutes after rinsing. Eighteen healthy subjects participated in each study. In the first study, following a 24-hour no-oral hygiene period, subjects received a 10-minute ultrasonic scaling of a randomly chosen half mouth, rinsed with either Cool Mint Listerine or a control, and received an ultrasonic scaling of the remaining half mouth. During each scaling period, aerosolized bacteria were collected on a sterile filter using a modified air-sampling device. The filters were overlaid on culture media, incubated aerobically, and colonies were counted. The second study followed the same basic design except that ultrasonic scaling was done for 5 minutes, and the post rinsing sampling was performed following a 40-minute simulated dental treatment period. Rinsing with Cool Mint Listerine resulted in a 92.1% reduction in viable bacteria in aerosols generated immediately after rinsing and a 91.3% reduction in aerosols generated 40 minutes after rinsing. These reductions were significantly greater than control (P = 0.0001). These studies suggest that preprocedural rinsing with Cool Mint Listerine Antiseptic may potentially reduce the risk of cross contamination in the dental operatory. PMID- 7880462 TI - Mechanical properties of direct and post-cured composites. AB - Surface mechanical properties (diametral tensile strength, Knoop hardness, and Rockwell Superficial indentation and recovery) and bulk mechanical properties (compressive strength and modulus of elasticity in compression) of seven composites were measured in vitro under two curing conditions (light-curing only and light-curing plus manufacturer's recommended post-curing). Post-curing improved the Knoop hardeness by 7 to 46% and diametral tensile strength by 15 to 39% of some of the composites. None of the composites had improved compressive strength and only two had an improved modulus of elasticity. PMID- 7880463 TI - Fracture resistance of complex amalgam restorations with peripheral shelves used as resistance features. AB - This in vitro study compared various peripheral shelves (steps) as resistance features for complex amalgam restorations. Three different sizes of peripheral shelves were evaluated: 1 mm x 1 mm, 2 mm x 2 mm, and 1 mm cervically x 2 mm pulpally. The resistance of these features was compared to a control group that utilized two amalgam pins. The 1 mm x 1 mm shelf provided significantly less resistance than the other groups. PMID- 7880464 TI - Dentin bonding system shelf life and bond strength. AB - The purpose of this study was to assess the shelf life of dentin bonding systems by means of bond strength testing. The systems evaluated were Mirage-Bond, All Bond and Tenure. Specimens were tested immediately, and 1, 2, 3, 4, 5 and 12 months after opening the kits. Flat dentin surfaces were created on 210 extracted human molars that had been stored in saline. Ten specimens were prepared for each dentin bonding system at each shelf time. Each material was prepared and placed following the manufacturer's instructions. Prisma MicroFine resin composite was then placed. Shear bond strength testing was conducted using a universal testing machine. A two-way ANOVA indicated a significant interaction between bonding system and storage time (F = 2.28, P = 0.01). Multiple comparison tests indicated statistically significant bond strength differences by storage time for All-Bond and Mirage-Bond. In addition, a comparison of bonding systems at each storage time revealed significant differences at three of the seven times. These results suggest that shelf life for two of the three dentin bonding systems may be significantly shorter than currently presumed. PMID- 7880465 TI - Effects of post-curing on mechanical properties of a composite. AB - The mechanical properties (diametral tensile strength, compressive strength, modulus of elasticity in compression, Knoop hardness, and Rockwell Superficial indentation and recovery) were measured for one light-cured composite (Herculite XRV) post-cured by five different conditions. The post-curing conditions were: boiling water, CRC-100, D.I.-500, Translux EC Light Box, and Triad 2000 with normal light curing as a control. Post-curing Herculite XRV significantly improved the diametral tensile strength (24-39%), Knoop hardness (8-22%) and Rockwell Superficial recovery (3-6%); decreased Rockwell Superficial indentation (0-19%) but did not affect the compressive strength significantly. Modulus of elasticity was not affected, except by the Translux EC Light Box, which increased the modulus by 33%. Post-curing Herculite XRV with the Triad 2000 and Translux EC Light Box produced the most improved properties. Water at 100 degrees C was the least effective of the post-curing methods. PMID- 7880466 TI - Bond strength of resin cements to microfilled composites. AB - The in vitro bond strengths of three resin cements and a light-cured and a laboratory-processed micro-filled composite were measured. Effects of two surface treatments, and three bond enhancers were analyzed. Resin cements were bonded to sandblasted composite substrates, stored at 37 degrees C in 100% humidity overnight, and debonded in tension. An analysis of variance revealed significant differences among bond strengths. Overall, the composite substrate had the largest effect on bond strength, followed by bond enhancer, cement and, finally, surface treatment. Mean bond strengths ranged from 0.9 to 13.6 MPa. A combination of Concept, Dual Cement, phosphoric acid and Silane produced the lowest mean bond strength (0.9 MPa), while EOS, Dual Cement, hydrofluoric acid, and Heliobond produced the highest recorded mean bond strength (13.6 MPa). In general, the highest bonds were produced using the light-cured composite (EOS), the acrylic monomer (Special Bond II) or the dimethacrylate monomer (Heliobond), the adhesive cement (CR Inlay Cement), and surface treatment with hydrofluoric acid (Comp Etch). Most of the bond failures (86%) with the laboratory-cured microfilled composite were adhesive. With the light-cured composite, 69% of the failures were mixed adhesive-cohesive types. PMID- 7880467 TI - The antimicrobial activity of Prevention mouthrinse. AB - Prevention mouthrinse was designed to serve as a vital supplement to normal oral hygiene procedures. To determine the antimicrobial potency of this mouthrinse, minimal inhibitory concentrations (MICs), bactericidal kinetics, and short-term exposure studies were conducted. A spectrum of oral microorganisms was employed in this investigation: Streptococcus sanguis, Streptococcus anginosus, Streptococcus mutans, Actinomyces viscosus, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Eikenella corrodens, Porphyromonas gingivalis, Serratia marcescens and Candida albicans. Microorganisms were cultured in standard enriched media and under appropriate atmospheric conditions. Inhibition assays were conducted in tubes, with each mouthrinse dilution assayed in triplicate. MIC determinations revealed that all of the microorganisms studied were highly susceptible to Prevention mouthrinse, with MICs ranging from 16-fold to 128-fold dilutions. Bactericidal kinetics assays showed rapid killing of the test organisms in the presence of the mouthrinse. Brief (5-minute) exposure of S. mutans to 8-fold diluted mouthrinse resulted in a substantial delay in growth. Under the constraints of this type of study, Prevention mouthrinse exhibited potent antimicrobial activity against all of the microorganisms studied. We support the notion that Prevention mouthrinse may be a valuable supplement to normal oral hygiene procedures. A 6-month clinical trial assessing the in vivo efficacy of Prevention mouthrinse is currently being conducted. PMID- 7880468 TI - Influence of aluminum oxalate solutions acidity and conditioning times on resin bond strength to enamel. AB - The present investigation demonstrated that variations in pH between 0.8 and 2.1 and in the duration of etching with an aluminum oxalate/glycine conditioning solution between 5 and 120 seconds has no influence on the retentive strength of restorative polymer to enamel, although the micromorphological appearance of enamel is clearly affected. The lower the pH of and the longer the etching time with the conditioning solution, the more pronounced is the roughness pattern generated. SEM inspection of the fracture sites following debonding of shear bond strength specimens verified consistently cohesive failure in resin close to the interface. PMID- 7880469 TI - Alloy particle shape and sensitivity of high-copper amalgams to manipulative variables. AB - Compressive strength, dimensional change during hardening and residual mercury content of three high-copper spherical particle amalgams (Tytin, Logic and Valiant), two admix amalgams (Dispersalloy and Permite C) and a conventional lathe-cut amalgam (New True Dentalloy) were determined as a function of condensation pressure and trituration time. The properties of the three amalgams containing non-spherical particles were markedly dependent on condensation pressure in the range 3 MPa to 14 MPa. Specimens condensed at 3 MPa showed substantially lower strength, greater expansion during hardening and higher residual mercury contents than did specimens condensed at 14 MPa. The three high copper spherical particle amalgams, on the other hand, were comparatively insensitive to condensation pressure. Variations in trituration time between 5 and 12 seconds had little effect on the properties of any of the amalgams. PMID- 7880470 TI - Variation in condensation pressure during clinical packing of amalgam restorations. AB - Clinical measurements were made of the condensation pressures applied by a specialist prosthodontist to each amalgam increment during the packing of two pinned Class II restorations. The technique employed involved taking simultaneous video recordings of the operative procedures and the output of a strain gauge stress measuring system attached to the plugger. The condensation pressure applied during each thrust of the plugger could then be related directly to a particular stage of the packing process. In Cavity A, a maxillary left second premolar, an "admix" amalgam containing both spherical and lathe-cut particles was used while Cavity B, a mandibular right first molar, was filled with a spherical particle amalgam. The measurements indicated that the condensation pressures applied decreased substantially as the filling of each cavity proceeded. A marked reduction accompanied the change from a 1.5 mm diameter to a 2.5 mm diameter plugger but in addition, the dentist modified the force applied to each plugger according to the particular task which he was undertaking. For Cavity A, the condensation pressure applied during the filling of the base of the mesial proximal box was 12.6 +/- 1.9 MPa whereas the final increment was subjected to a condensation pressure of only 2.2 +/- 0.7 MPa. Corresponding figures for Cavity B were 7.6 +/- 2.0 MPa and 1.9 +/- 0.5 MPa. PMID- 7880471 TI - A new approach to salvaging an existing fixed partial denture. AB - This case report describes the clinical procedures for salvaging a serviceable fixed partial denture (FPD) that deteriorated because of cement dissolution beneath the distal retainer. After removal of the FPD it was noticed that the "core reconstruction" was dislodged (the prefabricated post remained in the canal and required removal). A two-stage casting procedure that differed from reported techniques was customized to fit a cast post and core to the prepared root canal and retainer. The FPD was recemented and has been functioning satisfactorily for over 3 years. PMID- 7880472 TI - Dental fees. AB - Traditional economic theories impact on the viability of a practice. Yet the relationships between revenues generated and dental service fees are more complex than traditionally envisaged. Whereas long-term fee strategies and short term tactics may be instituted to stimulate service demands, the significance of non fee determinants (e.g. professional skills) cannot be underestimated. PMID- 7880473 TI - Latex reactions in an adult dental population. AB - A review of the medical histories of 300 adult patients presenting for emergency dental care at a dental college revealed no individuals who identified themselves as allergic to latex. A 32-item survey was distributed to adult dental patients receiving care at the dental school. 323 patients volunteered to complete the questionnaire. 3.7% of the patients reported adverse reactions associated with wearing latex gloves. However only 8.8% of the patient population reported work related latex glove use. The reported incidence of sensitivity to latex products such as rubber dam material and condoms was equal to that associated with gloves, and slightly lower in the case of enema tips (2.8%) and balloons (2.5%). Sensitivity to rectal and/or vaginal examination with latex gloves was reported by 5.5% of the population. Predisposing factors to reported latex sensitivity found to be significant (P < .01) included a history of eczema and a familial history of allergies. No significant differences were found with regard to age or gender. Only two individuals reported severe systemic symptoms related to latex exposure. Data suggest that careful questioning of patients regarding a history of sensitivity to multiple latex-based products can facilitate the identification of possibly latex sensitive individuals, thus preventing latex-related allergic reactions in the dental operatory. PMID- 7880474 TI - Antiseptic mouthrinse-induced microbial cell surface alterations. AB - This study determined the effect of an essential oil-containing mouthrinse, Listerine Antiseptic, on microbial cell surface morphology using scanning electron microscopy. Twenty-four hour cultures of C. albicans, A. viscosus, S. sanguis, F. nucleatum, and A. actinomycetemcomitans were harvested and washed in buffer. Triplicate samples were overlaid on poly-L-lysine coated coverslips, immersed in either Listerine or buffer for 30 seconds, fixed in glutaraldehyde followed by post-fixing in 1% osmium tetroxide, dehydrated, and embedded in Peldri II. Exposure of the microorganisms to Listerine Antiseptic for 30 seconds resulted in distinct morphological alterations of cell surfaces suggestive of loss of cell surface integrity. The extent of alteration varied among the structurally different species; cell surface roughening was mild in S. sanguis but extensive in the other microorganisms which developed distinct surface blebs and other abnormalities after the 30-second exposure. These results suggest that a brief exposure to Listerine produces significant morphological changes which may be associated with cell death and may help explain the alteration of surface associated activities demonstrated in previous studies. PMID- 7880475 TI - Dimensional changes occurring in a glass-ionomer cement. AB - The dimensional changes occurring when glass ionomer cements are exposed both to desiccating and moist conditions were investigated. All work was done at 23 degrees C. The effect of time allowed for cements to mature before exposure to the test conditions was studied as was the effect of adding cellulose ethers. The contraction of glass ionomer cements under desiccating conditions was far greater than the expansion by water absorption. Increase of the time allowed for the cements to mature reduced the extent of this effect markedly. The addition of cellulose ethers to cement mixes was only moderately effective in reducing dimensional change. PMID- 7880476 TI - Desensitizing effects of Gluma and Gluma 2000 on hypersensitive dentin. AB - The aim of this clinical trial was to investigate the effects of topical applications of Gluma 3 Primer or Gluma 2000 conditioning solutions on hypersensitive erosion/abrasion lesions. Thirty-four patients were included in the trial with at least two teeth each presenting severe sensitivity. From a total of 116 teeth, 40 were treated with Gluma 3 Primer, 42 with Gluma 2000 Conditioner and 34 served as the control. Sensitivity was recorded as response to tactile and cold air stimuli prior to treatment as baseline, immediately after the topical application of the agents, after 1 week, 1 month and 6 months. Both Gluma groups showed a highly significant reduction in sensitivity between baseline and postoperative pain scores (P < 0.05) and between the postoperative and the 1-week responses (P < 0.05). The sensitivity scores were not different between 1 week and 6 months. In the control group, no pain reduction was registered between baseline and up to 1-month recall. After 6 months, however, the sensitivity was spontaneously slightly reduced. At the end of the 6-month observation time, 29 Gluma and 31 Gluma 2000 treated teeth no longer showed dentin sensitivity. PMID- 7880477 TI - Etchant composition and bond strength to dentin. AB - This in vitro study examined the effects of three different types of acid etchants on the bond strengths of three dentin bonding systems. The etchant free of both silica and oxalate provided the highest bond strengths for all three systems. Use of the etchant containing oxalate resulted on the lowest bond strengths for all three systems. It is suggested that bond strengths vary as a consequence of deposition onto the dentin surface of various minerals or salts found in the etchants. It is recommended that if treatment of dentin with acids is indicated it should probably be done with those etchants containing neither silica nor oxalate. PMID- 7880478 TI - Bond strengths of porcelain repair adhesive systems. AB - This study compared the shear bond strength of resin composite bonded to porcelain with six commercial porcelain repair adhesive systems. The porcelain repair systems tested were: All-Bond 2, Clearfil Porcelain Bond, Ceram-Etch, C&B Metabond with Etch-Free Primer, Scotchprime, and Ultradent Porcelain Etch. Resin composite cylinders were bonded to primed porcelain surfaces and the specimens were thermocycled and stored in distilled water at 37 degrees C for 36 days. After storage, a testing machine was used to deliver a shear force parallel to the porcelain/composite interface. Mean load to failure was calculated for each group and the fracture location was noted. Results demonstrated cohesive porcelain failures and high bond strengths for All-Bond 2, Clearfil, Metabond, Scotchprime, and Ultradent. Statistical analysis revealed significantly lower bond strengths for the group that failed at the porcelain/composite interface. PMID- 7880479 TI - Shear bond strength and microleakage of new dentin bonding systems. AB - The aim of this study was to evaluate the shear bond strength and microleakage of three new bonding agents. Eight specimens were prepared from each material and shear bond strength was measured using a universal testing machine at crosshead speed of 0.5 mm/minute. Fracture pattern was studied by stereomicroscope and scanning electron microscope (SEM). For the microleakage test, Class V cavities were prepared in the buccal or lingual surface of extracted lower molar teeth and restored with resin composites after application of the accompanying adhesives. The restored teeth were loaded at 125 N for 5000 cycles in a dye solution, sectioned and inspected for microleakage. Bond strengths of 17.7 +/- 4.1, 16.3 +/ 3.8, 15.7 +/- 5.8 MPa were measured for Scotchbond Multi-Purpose, Clearfil Liner Bond and Optibond respectively. Restorations of Scotchbond MP and Clearfil LB showed no leakage, while those of OptiBond showed leakage in only one out of eight fillings. PMID- 7880480 TI - Bond strength of resin-reinforced glass ionomer cements after enamel etching. AB - This study evaluated the shear bond strength of resin-reinforced glass ionomers to enamel etched or unetched. Human, non-carious extracted permanent molars stored in distilled water were used. Flat buccal and lingual enamel surfaces were ground wet on 600-grit silicon carbide paper. The teeth were then distributed at random into six groups of 5 teeth (10 surfaces) each: Group 1: Fuji II LC, no enamel etching; Group 2: Fuji II LC, enamel etched with 10% phosphoric acid for 10 seconds; Group 3: Dyract, no enamel etching; Group 4: Dyract, enamel etched with 10% phosphoric acid for 10 seconds; Group 5: Photac-Fil, no enamel etching; Group 6: Photac-Fil, enamel etched with 10% phosphoric acid for 10 seconds. Cylindrical samples of the glass ionomers were prepared in plastic molds and bonded to the enamel surface according to the manufacturers' instructions. All samples were placed in distilled water for 24 hours, and sheared with an Instron at a crosshead speed of 0.5 mm/minute. The results (in MPa) were: Group 1: 11.29 +/- 4.84; Group 2: 19.64 +/- 5.43; Group 3: 8.26 +/- 3.61; Group 4: 22.04 +/- 5.40; Group 5: 2.05 +/- 3.05; Group 6: 9.12 +/- 6.61. ANOVA and Student-Newman Keuls procedure revealed that on etched enamel, Fuji II LC and Dyract had a significantly higher bond strength than all the other groups tested (P < 0.0001), but not significantly different between each other. With these two groups, cohesive failure within the material was recorded in all samples while in the unetched samples, all specimens displayed an adhesive failure (glass ionomer enamel interface). All samples with Photac-Fil, with or without enamel etching had adhesive failures. PMID- 7880481 TI - Effects of etching time on enamel bond strengths. AB - This study evaluated the effects of etching time on bond strengths of composite to enamel. Proximal surfaces of extracted molars were etched with either a conventional etchant (35% phosphoric acid) or one of two dentin/enamel conditioners, 10% maleic acid (Scotchbond Multi-Purpose Etchant), or a solution of oxalic acid, aluminum nitrate, and glycine (Gluma 1 & 2 Conditioner). Each agent was applied for 15, 30, or 60 seconds. Specimens etched with 35% phosphoric acid had the highest mean bond strengths at each etching time. At the manufacturer's recommended application times, the other two agents gave significantly lower shear bond strengths than phosphoric acid. PMID- 7880482 TI - Mercury in solution following exposure of various amalgams to carbamide peroxides. AB - Carbamide peroxide (CP) is an easily administered material for whitening teeth. Although toxicological research on CP alone has revealed no adverse health effects, possible oxidation and release of mercury from amalgams have not previously been investigated. This research evaluated the quantitative release of mercury from amalgams into solution by CP. CP preparations can generally be divided into two classes based on the presence or absence of carbopol, an oxygen releasing inhibitor. Rembrandt (R), a 10% CP with carbopol and White and Brite (WB), a 10% CP without carbopol were used in this study. Four different types of amalgams [Dispersalloy (D), Sybraloy (S), Tytin (T) and Valiant Ph.D. (V)] were selected. Uniform samples of the four amalgams were prepared and stored at 37 degrees C for 1 week. Vials of saline (10 ml), R and WB were prepared. R and WB were mixed with saline to a 50:50 solution to reduce viscosity and facilitate stirring. Magnetic teflon coated stir bars were placed in all vials, and one amalgam specimen was placed in each non-control vial. After being stirred for 8 hours, solutions were analyzed for elemental mercury content using a Jerome Gold Film Mercury Analyzer. All background mercury levels were zero, but following the experiment there were significantly higher amounts of mercury in the CP solutions as compared to the 100% saline solutions. These results suggest there is an active oxidation of the amalgam releasing mercury ions into solution. PMID- 7880483 TI - Toxicity of two carbamide peroxide products used in nightguard vital bleaching. AB - This study evaluated the effects of two generic classes of 10% carbamide-peroxide (CP) oxygenating agents (currently under clinical assessment for nightguard vital tooth bleaching) for lethality and genetic mutation after oral administration to mice, and for cellular cytotoxicity to mouse fibroblasts in vitro. The single dose LD50 values for a non-carbopol-containing CP (Gly-Oxide) and a carbopol containing CP (Proxigel) in mice were found to be 143.8 mg/kg and 87.2 mg/kg, respectively. Genotoxicity, as measured by the Mouse Micronucleus test for mutagenicity, was negative for both 10% CP agents in comparison with positive and negative controls. Cytotoxicity as measured in the L929 fibroblast lysis assay resulted in 50% killing of L929 fibroblasts at 0.62 for the non-carbopol containing CP and 1.88 mmol/L for the carbopol-containing CP. Both 10% CP agents were compared with seven widely-used dental products in the L929 fibroblast lysis assay and found to be no more toxic than these products. PMID- 7880484 TI - The magnitude of interproximal spaces between adjacent teeth. AB - Previous studies have shown that the human resting dentition naturally exhibits slight interproximal spacing between 80% to 90% of all adjacent teeth. The purpose of this study was to measure occurrence and dimension of interproximal spacing. Pieces of shim stock of various thicknesses were used to measure the dimension of interproximal spaces between natural or restored approximating tooth surfaces in 40 human subjects. The midline was frequently found to exhibit the largest space, and the dimension of the spacing was found to be greater in anterior teeth than posterior teeth. The canine-premolar spaces were also relatively large. The magnitude of interproximal tooth spacing was not related to gender or age. Results indicate that the position of teeth is naturally adjusted to maintain interproximal spacing. Interproximal spacing may allow for physiological movement to increase tolerance to trauma and improve tactile sensation. PMID- 7880485 TI - The need for continuing education in dentistry. PMID- 7880486 TI - [The legal consequences of alcohol-induced accidents at work and in street traffic]. AB - The publisher describes the possible problems arising, in addition to the legal consequences from an accident after alcohol consumption. The publisher refers to accidents at work or on the road during which personal injury or material damage is caused. PMID- 7880487 TI - [Epidemiologic study of CDT (carbohydrate-deficient transferrin) and other indicators of alcohol problems in high blood alcohol German automobile drivers]. AB - Alcoholism indicators like CDT, GGT, methanol and acetone + isopropanol were measured in blood samples of male German alcoholized car drivers who were at least 18 years old and had a minimum BAC of 0.80 g/kg (per mille). The investigation of 534 cases reflects German conditions. The study proves that a BAC of 1.60 g/kg (per mille) is no appropriate criterion for the assumption of alcohol problems. Alcohol problems appeared significantly more often in cases where BAC levels were 2.0 g/kg (per mille) or higher. It is thought that a total of 20 to 25% of the alcoholized drivers have serious alcohol problems. Amongst those the proportions were as follows: 8% amongst the under 30s and one third amongst tho over 30s. 40% of all drivers with alcohol problems had BACs below 1.6 g/kg (per mille) during the offence. CDT has proved to be a valuable addition to the other indicators when detecting alcoholism in DWI drivers. PMID- 7880488 TI - [Detection of amphetamine derivatives in chemical toxicological studies 1987-1993 in the greater Frankfurt area]. AB - Chemical-toxicological testing during the period from 1987 to 1993 revealed a remarkable increase in amphetamine positive cases in the greater Frankfurt area. Amphetamine abuse is particularly worrying in car drivers, where the proportion of amphetamine positive cases increased from 0.49% in 1987 to 9.40% in 1993. Considering the fact, that the only samples tested were the ones of drivers exhibiting an impaired driving performance, the number of cases remaining undetected is most certainly higher. This study also demonstrated that amphetamine derivatives are rarely consumed on their own. In most cases (80%) they are consumed in conjunction with cannabis. The additional use of tranquillisers occurred more often than that of cocaine. It seems that amphetamine abuse plays only a minor role with heroin users. This is emphasised by the low number of drug fatalities. PMID- 7880489 TI - Congener production in blood samples during preparation and storage. AB - The possibility of congener production in blood during storage was studied. The material consisted of 216 blood specimens in which ethanol was not detected. We divided the specimens into two groups, A and B. Group A: 97 specimens were stored at 4 degrees C until alcohol analysis, and only exposed shortly to room temperature during the aseptic preparation for analysis. Group B: 119 specimens were stored at 17 degrees C until alcohol analysis were performed, and the handling during preparation was not aseptic. All specimens were subsequently stored at 4 degrees C. After three to twelve months of storage the blood specimens were analyzed for congeners. None of the forensic important congeners (n-propanol, isobutanol, or butanol-2) were detected in Group A, whereas in Group B n-propanol was detected in fourteen of the specimens, isobutanol in sixteen, and butanol-2 in two specimens. PMID- 7880490 TI - [The self concept and personality structure of alcohol intoxicated drivers: how do they see themselves, and how are they judged by others?]. AB - Assessing the problem of "alcohol in road traffic" it becomes apparent that most offenders have high BACs (in excess of 1.6 per mille) and that they are repeating offenders. It can therefore be assumed that those people are drink-drivers, which means that, when assessing the offence, the offender's personality as a whole has to be taken into consideration. The DUI offenders themselves usually justify the offence by balming it on the circumstances of a given situation. On the basis of this discrepancy, the published study deals with the question of whether there are any differences between the way DUI offenders judge their personality and self concept and the way other people do. This also leads to the questions of whether the number of offences play a role or not. The self image of 60 male DUI offenders was rated by means of the Giessen test and the Frankfurt self concept scales "problem solving", "confidence in behaviour and decision making", as well as "judgement by others". For the outside judgement, 60 male volunteers were asked to judge DUI convicted drivers. It showed that the DUI convicted drivers assessed their personality to be no different than that of the average person. Their self concept was characterised by positive attributes. However, the outside judgement showed them to be less socially responsive, lacking self control, as well as rather dominant, depressive, reserved and rather inhibited in heterosexual relationships. The self judgement changes with an increasing number of offences, as does the outside judgement to an even greater extend. The latter turns into a more negative judgement. Regarding the self concepts, only the outside judgement proved to be more negative. The number of convictions didn't influence the DUI offenders' self estimation. PMID- 7880491 TI - [Descriptive study of dorsal lumbago among nursing personnel in a general hospital]. PMID- 7880492 TI - [Ethics committees: what areas for discussion?]. PMID- 7880493 TI - [The introduction of the minimum data set in the hospital financial management]. PMID- 7880494 TI - Forum: home care in the U.K. PMID- 7880495 TI - Recent advances in wound management in the U.K. PMID- 7880497 TI - Focus on the U.K. PMID- 7880496 TI - Draft guideline published on preventing the spread of VRE infections. Hospital Infection Control Practices Advisory Committee. PMID- 7880498 TI - Forum: infection prevention in the home health setting. PMID- 7880499 TI - Critical pathways. PMID- 7880500 TI - A brief history of sterilization. PMID- 7880501 TI - Sterilization futures. PMID- 7880503 TI - Flash sterilization. PMID- 7880502 TI - Forum: disinfection & sterilization procedures used in hospitals in the U.S. PMID- 7880504 TI - Forum: methods of sterilization and disinfection--some of the latest views. PMID- 7880505 TI - Focus on Japan: overview of health care system. PMID- 7880506 TI - Infection control measures and infection management nurses in Japan. PMID- 7880507 TI - The role of the electroencephalogram in assessing memory function under general anesthesia. PMID- 7880508 TI - Investigation of the pharmacokinetics and analgesic effects of an intramuscular injection of sustained-release sufentanil for postoperative pain: an open study. AB - STUDY OBJECTIVES: To investigate the pharmacokinetics after an intramuscular (IM) injection of sufentanil in thin vegetable oil in postsurgical patients and to determine whether sustained-release IM sufentanil can provide safe and sufficient analgesia of long duration in these patients. DESIGN: Open study. SETTING: University hospital. PATIENTS: 10 ASA physical status I and II patients aged 18 to 65 years who were scheduled for elective surgery. INTERVENTIONS: All patients were premedicated with lorazepam and anesthetized with a general anesthetic technique containing nitrous oxide, fentanyl, and isoflurane. As soon as significant pain [visual analog scale score of 5 or greater (range, 0 = no pain to 10 = worst pain imaginable)] occurred during the early postoperative period, the patient received an IM injection of sustained-release sufentanil. MEASUREMENTS AND MAIN RESULTS: During the first 48 hours following surgery, blood samples were taken for determination of plasma sufentanil concentrations. Blood pressure, heart rate, respiratory rate, pain scores, and sedation scores were documented at the same time. The IM administration of sufentanil in thin vegetable oil provided sufficient pain relief, although the onset of analgesia was rather slow (+/- 1 hour). The analgesic effect was still apparent 48 hours later. Plasma concentration of sufentanil at the different time points varied from 0.021 to 0.142 ng/ml, with a mean maximal peak concentration of 0.103 ng/ml. The plasma concentration 48 hours after injection varied from 0.026 to 0.074 ng/ml. CONCLUSIONS: Although an IM injection of sufentanil in thin vegetable oil is effective for postoperative pain relief, it is associated with wide interindividual variability in plasma concentration of sufentanil and long duration of action. PMID- 7880509 TI - Central venous catheter placement using the ECG-guided Cavafix-Certodyn SD catheter. AB - STUDY OBJECTIVE: To evaluate the clinical use of a new ECG-guided central venous catheter with regard to positioning in the superior vena cava (SVC). DESIGN: Prospective study. SETTING: Operating rooms of a university hospital and a general hospital. PATIENTS: 89 elective and emergency adult surgical patients requiring central venous catheterization perioperatively. INTERVENTIONS: We performed ECG-guided placement of the central venous catheter from several insertion sites. After we observed an intra-atrial p-wave (p-atriale), the catheter was withdrawn 3 cm back into the SVC. Postoperative anterior-posterior chest radiographs were performed for verification of tip localization. MEASUREMENTS AND MAIN RESULTS: In all 81 patients who exhibited a p-atriale that reverted to a normal-size p-wave (p-SVC) after withdrawal of the catheter 3 cm, the tip was located in the SVC or the SVC-right atrial junction on the chest radiograph. In 7 of the 8 cases without a p-atriale, the catheter tip was shown to be located at an incorrect position on the chest radiograph. The size of the p atriale was always at least twice that of the p-SVC. CONCLUSIONS: Use of this wire-conducted intravascular ECG signal is a reliable tool for positioning the central venous catheter via various insertion sites. The technique proved to be an inexpensive, easy, and clear method. When a p-atriale is seen, uncomplicated insertions do not require radiologic guidance to control catheter tip position. PMID- 7880510 TI - Pretreatment with sedative-hypnotics, but not with nondepolarizing muscle relaxants, attenuates alfentanil-induced muscle rigidity. AB - STUDY OBJECTIVE: To evaluate and compare the efficacy of various pretreatment agents to attenuate or prevent opioid-induced muscle rigidity using a well established, previously described clinical protocol. DESIGN: Prospective, controlled, single-blind, partially randomized study. SETTING: Large medical center. PATIENTS: ASA physical status I-III patients undergoing elective surgical procedures of at least 3 hours' duration. INTERVENTIONS: The effect of pretreatment with nondepolarizing muscle relaxants (atracurium 40 micrograms/kg or metocurine 50 micrograms/kg), benzodiazepine agonists (diazepam 5 mg or midazolam 2.5 mg), or thiopental sodium 1 mg/kg on the increased muscle tone produced by alfentanil 175 micrograms/kg was compared with a control group (given no pretreatment). MEASUREMENTS AND MAIN RESULTS: Rigidity was assessed quantitatively by measuring the electromyographic activity of five muscle groups (biceps, intercostals, abdominals, quadriceps, and gastrocnemius). Rigidity also was rated qualitatively by attempts to initiate and maintain mask ventilation, attempts to flex an extremity, and the occurrence of myoclonic movements. Pretreatment with the two nondepolarizing muscle relaxants had no effect on the severe muscle rigidity produced by high-dose alfentanil. Whereas thiopental was only mildly effective, the benzodiazepines midazolam and diazepam significantly attenuated alfentanil rigidity (p < 0.05). CONCLUSION: This study suggests that benzodiazepine pretreatment is frequently, but not always, effective in preventing opioid-induced muscle rigidity. PMID- 7880511 TI - Midazolam does not antagonize fentanyl-mediated analgesia in surgical patients. AB - STUDY OBJECTIVE: To determine whether midazolam possesses a clinically significant antianalgesic action in surgical patients. DESIGN: Randomized, controlled study. SETTING: Inpatient anesthesia at a university department of neurosurgery. PATIENTS: 2 groups of 10 patients each who were scheduled for supratentorial brain surgery, did not have elevated intracranial pressure, and were free from systemic disease. INTERVENTIONS: Patients underwent anesthesia induction with hexobarbital, succinylcholine, and pancuronium; anesthesia was maintained with injections of droperidol-fentanyl (Group 1) or with midazolam fentanyl (Group 2) following a predetermined repetitive dosing schedule, such that fentanyl 0.1 mg was injected upon predominant increases in heart rate, whereas droperidol 2.5 mg or midazolam 2.5 mg was injected upon increases in blood pressure. MEASUREMENTS AND MAIN RESULTS: Duration of anesthesia and invasiveness of surgery were similar in both groups. The amount of fentanyl required was 0.55 +/- 0.18 mg/hr (mean +/- SD) in Group 1 and 0.53 +/- 0.17 mg/hr in Group 2. Injections of droperidol 7.5 +/- 3.4 mg/hr (Group 1) and midazolam 5.9 +/- 2.3 mg/hr (Group 2) were administered intraoperatively. This redosing regimen was associated with uninterrupted hemodynamic stability, indicating comparable and adequate anesthetic depth. Plasma concentrations of metabolites and hormones indicative of humoral stress activation did not differ between groups. CONCLUSION: Under these clinical conditions, the administration of midazolam, when compared with droperidol, was not associated with signs of any antagonistic or antianalgesic action toward fentanyl-mediated analgesia. PMID- 7880512 TI - Subarachnoid bupivacaine blockade decreases midazolam and thiopental hypnotic requirements. AB - STUDY OBJECTIVE: To test the hypothesis that subarachnoid bupivacaine blockade decreases hypnotic requirements for thiopental sodium and midazolam. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Teaching hospital. PATIENTS: 53 nonpremedicated ASA physical status I and II adult male patients scheduled for elective lower abdominal, pelvic, or lower limb surgery. INTERVENTIONS: Intravenous injections of midazolam or thiopental were administered with or without subarachnoid bupivacaine blockade (12.5 mg) at the L3-L4 level. Thiopental or midazolam hypnotic requirements were determined using loss of ability to open eyes in response to verbal command as an endpoint. The thiopental requirements were determined by titration; the midazolam requirements were determined from dose-response curves obtained with bolus injections of predetermined doses of the drug. MEASUREMENTS AND MAIN RESULTS: Subarachnoid bupivacaine blockade decreased the hypnotic dose of thiopental from 3.40 +/- 0.68 mg/kg (mean +/- SD) with a dose range of 2.3 to 4.5 mg/kg (intramuscular saline) to 2.17 +/- 0.48 mg/kg with a dose range of 1.3 to 2.8 mg/kg (p < 0.005 for the difference). The ED50 value of midazolam decreased with the bupivacaine blockade, from 0.23 mg/kg (95% confidence limits: 0.08 to 0.38 mg/kg) to 0.06 mg/kg (0.01 to 0.14 mg/kg), with p < 0.0001 for the difference. CONCLUSION: Subarachoid bupivacaine blockade decreases hypnotic requirements for both thiopental and midazolam. The results suggest that the reduction in hypnotic requirements is due to the decrease in afferent input induced by spinal anesthesia. PMID- 7880513 TI - Intraoperative pulse oximetry: frequency and distribution of discrepant data. AB - STUDY OBJECTIVE: To determine the types of discrepant data during intraoperative pulse oximetry and their frequency and duration. DESIGN: Prospective study. SETTING: University medical center. PATIENTS: 46 consecutive ASA physical status I-III patients undergoing general anesthesia for elective surgical operations. MEASUREMENTS AND MAIN RESULTS: With an integrated computer algorithm on the pulse oximeter and another computer linked to it, data were screened and the frequency and distribution of the following oximeter signals recorded: absent; low quality or interrupted, as detected by the pulse oximeter algorithm; nonphysiologic, identified by the personal computer as a heart rate change greater than 10 beats per minute within 2 consecutive 2-second samples, with no similar abrupt change reported simultaneously on ECG. The number of episodes per hour of discrepant oximeter data and the duration of the episodes were recorded by phase of anesthesia: induction, maintenance, and emergence. Discrepant data occurred most frequently and lasted longest during emergence (p < 0.05); the majority of episodes of discrepant data during emergence lasted less than 12 seconds. Excluding discrepant data that lasted less than 12 seconds decreased the frequency of discrepant data by 63% and excluding those that lasted less than 30 seconds decreased the frequency of discrepant data by 93%. CONCLUSIONS: Pulse oximeters frequently report discrepant data intraoperatively, most frequently during emergence from anesthesia. An alarm delay triggered by discrepant data and lasting 12 to 30 seconds would keep most discrepant data from becoming false alarms and, thus, may reduce distracting sound pollution in the operating room. PMID- 7880514 TI - EEG-controlled "overdosage" of anesthetics in a patient with a history of intra anesthetic awareness. AB - In spite of the ever-growing pharmacologic arsenal available for induction and maintenance of anesthesia, to our knowledge no treatment regimen exists that will provide full protection against intraoperative awareness. To date, no single monitoring technique is able to detect awareness or predict recall. Although the frequency of these complications is rare, the occurrence of any such event can be very distressful for the patient. Based on our clinical experience with a patient with a history of recall and a marked resistance to benzodiazepines, we present electroencephalogram-based anesthetic management as a technique to address this difficult problem. PMID- 7880515 TI - A hemothorax after thoracic epidural anesthesia. AB - A case of a hemothorax that occurred after thoracic epidural anesthesia is described. This situation might have been caused by accidental puncture of the intercostal vessel and visceral pleura by a Tuohy needle. The risk of causing a pneumothorax and/or hemothorax must be kept in mind when attempting thoracic epidural anesthesia. PMID- 7880516 TI - Pneumocephalus following the treatment of a postdural puncture headache with an epidural saline infusion. AB - We report a case of pneumocephalus following the attempted treatment of a postdural puncture headache by a continuous epidural saline infusion. Within 1 hour of infusion, symptoms of a severe headache, nausea, and vomiting prompted a computerized tomographic scan of the head that showed 12 to 15 ml of air in the cranium. The epidural space was located easily with the loss-of-resistance technique using 3 ml of air. A saline bolus and infusion were initiated after confirmation of correct placement of the epidural catheter. We suggest that air passed from the negative-pressure epidural space through the dural puncture created by the diagnostic spinal tap, producing a pneumocephalus. PMID- 7880517 TI - The anesthetic management of a patient with chromosome 10qter deletion syndrome. AB - Terminal deletions of chromosome 10q are uncommon. The resulting syndrome includes cardiac and facial anomalies, urogenital abnormalities, limb defects, and mental retardation. Most affected infants require surgical correction of these anomalies. Presented are features inherent in the syndrome that will aid the anesthesiologist in the perioperative management of such patients. PMID- 7880518 TI - Assessment of masseter spasm complicated by a faulty temperature probe. AB - During palatoplasty on a 9-year-old girl with no personal or familial history of malignant hyperthermia, the temperature monitor reported an increase in temperature. Additionally, the surgeon thought the patient's jaw muscle was in spasm. While preparations were made for treatment of malignant hyperthermia, the temperature probe was tested and found to be defective. When it was replaced, the patient's temperature was within normal range. When the temperature probe was tested 6 days later, it was working properly. The cause of the problem may have been moisture in the connection between the probe and the exterior cable, which eventually evaporated. Decision algorithms can assist in such situations to distinguish between a medical problem and a mechanical problem with the monitor. PMID- 7880519 TI - Postanesthesia monitoring revisited II. PMID- 7880520 TI - Monitoring anesthetic depth during laryngeal mask anesthesia. PMID- 7880521 TI - Gastric irritation after ketorolac Bier block for treating reflex sympathetic dystrophy. PMID- 7880522 TI - More on submandibular endotracheal intubation for panfacial fractures. PMID- 7880523 TI - Cell fate decisions in the grasshopper central nervous system. AB - The central nervous system (CNS) of grasshopper embryos is similar in organization to the embryonic Drosophila CNS, but its neurons are much larger. The recent development of a culture system in which extensive CNS development occurs has allowed new types of experiments to be performed, including perturbation of gene expression within single neuroblast lineages. PMID- 7880524 TI - Regulatory mechanisms that coordinate skeletal muscle differentiation and cell cycle withdrawal. AB - Skeletal muscle differentiation entails the coupling of muscle-specific gene expression to terminal withdrawal from the cell cycle. Several models have recently been proposed which attempt to explain how regulated expression and function of myogenic transcription factors ensures that proliferation and differentiation of skeletal muscle cells are mutually exclusive processes. PMID- 7880525 TI - Differentiation and self-renewal in the mouse gastrointestinal epithelium. AB - The mouse gut epithelium represents a dynamic, geographically well organized, developmental system for examining self-renewal and differentiation. Reagents are now available for identifying the molecular mechanisms that regulate cell fate in the gut, the migration-associated differentiation programs of its component cell lineages, and its axial patterning. Considerable attention needs to be paid to two variables when studying gastrointestinal epithelial cell biology: space and time. This has necessitated the use of normal, chimeric, and transgenic animals as experimental models. PMID- 7880526 TI - Hematopoietic growth factors and the regulation of differentiative decisions. AB - Hematopoietic growth factors control the growth and differentiation of hematopoietic progenitor cells and bind to specific receptors that are expressed on the surface of immature hematopoietic cells found in the bone marrow. Many studies have demonstrated that these growth factors stimulate cellular growth and division by receptor activation. More recently, it has become apparent that they also influence, either directly or indirectly, the process of cellular differentiation. PMID- 7880527 TI - Differentiation and cell death: lessons from the immune system. AB - The immune system provides a unique vantage point from which to view the interrelationship between differentiation and cell death, as apoptosis is a prominent feature of B- and T-lymphocyte development. Two common themes emerge from recent experimental observations. First, survival signals are crucial during the differentiation process. The upregulation of Bcl-2 during positive selection suggests that this molecule serves as a survival signal to maintain lymphoid homeostasis. Second, if cell death is repressed, cellular differentiation can occur in the absence of inductive signals. PMID- 7880528 TI - Insights into erythroid differentiation obtained from studies on avian erythroblastosis virus. AB - Analysis of the oncogenes v-erbB and v-erbA and their normal proto-oncogene counterparts has revealed several novel aspects of erythroid differentiation. A new erythroid progenitor capable of extended self-renewal has been described, tyrosine kinase receptors and steroid hormone receptors have been found to cooperate in controlling self-renewal, and dramatic alterations in the cell cycle have been found to accompany induction of terminal differentiation. PMID- 7880529 TI - Vitamin A, differentiation and cancer. AB - Retinoids, which are derivatives of vitamin A, have a variety of effects on normal cellular differentiation and on the process of carcinogenesis. A number of novel endogenous retinol metabolites have been identified recently. The response of many cell types to retinoid treatment is mediated by retinoid receptors, and involves changes in gene expression, cell growth and cell differentiation. The gene encoding one of the retinoic acid receptors is disrupted by the chromosome translocations associated with acute promyelocytic leukemia, and the expression of another is altered in epithelial tumors; both of these findings have important implications for the use of retinoids as anti-carcinogenic agents. It has been demonstrated recently that certain homeobox genes are regulated by retinoids; these genes may also prove to be useful agents for anti-carcinogenic therapies. PMID- 7880530 TI - Signal transduction in the budding yeast Saccharomyces cerevisiae. AB - As a key part of the mechanism which controls growth and division, cells are able to respond to a variety of intracellular and extracellular stimuli. Significant progress has been made in the understanding of the biochemical mechanisms underlying mating-factor signal transduction in Saccharomyces cerevisiae. Some of these mechanisms may be relevant to the regulation of other signal transduction pathways. PMID- 7880531 TI - Mammalian G1 cyclins. AB - D- and E-type cyclins regulate the progression of mammalian cells through the G1 phase of the cell cycle. The mechanisms responsible for the accumulation and activation of kinases dependent on cyclins D and E in both normal and cancerous cells have recently been uncovered. Overexpression of cyclin D1 protein as a consequence of genetic rearrangements, and deletions or mutations of the p16INK4 gene have been demonstrated in a large variety of human cancers, including breast and esophageal carcinomas, lymphomas, bladder carcinoma, pancreatic adenocarcinoma and familial melanoma. PMID- 7880532 TI - Cdk inhibitors: on the threshold of checkpoints and development. AB - The regulation of cyclin-dependent kinases is at the heart of cell cycle control and, by inference, the control of cell proliferation. Recent advances in regulation of these kinases have uncovered a group of small proteins that bind to and inhibit them, thus preventing cell cycle progression. Linking these proteins to tumor suppressor functions has provided a much sought after connection between cancer and cell cycle control. PMID- 7880533 TI - p53 and Rb: their cellular roles. AB - Within the past year considerable new insights have been gained into the roles the p53 and retinoblastoma tumour suppressors play in determining the fate of cells through their regulation of cell cycle progression, apoptosis and gene expression. Key advances have been achieved in the identification and characterization of functional domains and through functional knockout studies. PMID- 7880534 TI - DP and E2F proteins: coordinating transcription with cell cycle progression. AB - Transcriptional control during the G1/S transition is important in regulating cell cycle progression. The transcription factor DRTF1/E2F is believed to play a crucial role in this process by integrating the activity of the machinery that drives the cell cycle with the transcription apparatus. Being the point of convergence for growth-promoting and growth-inhibitory signals, it is a pivotal cellular target for molecules which subvert normal cell cycle control, such as oncoviral proteins. Recent studies have indicated that members of two distinct families of proteins, DP and E2F, interact combinatorially as DP/E2F heterodimers in DRTF1/E2F. The activities of both DP and E2F proteins are under cell cycle control, being influenced by the level of phosphorylation imparted through the cell cycle regulated activity of cyclin-dependent kinases. Both DP and E2F proteins are endowed with proto-oncogenic activity and, conversely, have been implicated in regulating apoptosis. Current evidence suggests therefore that the activity of DRTF1/E2F is instrumental in regulating progression through the cell cycle. PMID- 7880535 TI - How cells know they are in G1 or G2. AB - How does a cell know if it's in G1 or G2 and should proceed to S phase or mitosis? This is a restatement of the question of how a cell ensures mitosis is dependent upon S phase, and S phase is dependent upon mitosis. Several gene products have been identified which play important roles in maintaining these interdependencies. Central to these controls are oscillations between different complexes of cyclins and cyclin-dependent kinases. PMID- 7880536 TI - Cell cycle checkpoints. AB - Checkpoints help ensure that cell cycle events occur in the correct order. Studies on mammalian cells identified inhibitors of complexes of cyclins and cyclin-dependent kinases as components of cell cycle checkpoints and provide the first glimpse of the molecular pathways that prevent cells with damaged DNA from replicating their DNA. In embryos, the extent to which checkpoints arrest the cell cycle reflects the relative strength of inhibitory checkpoints and the machinery driving the cell cycle forward. PMID- 7880537 TI - Cdc2 regulatory factors. AB - A growing family of kinases and phosphatases controls the activity of the cyclin dependent kinase cdc2. The past year has seen the identification of the cdk activating kinase as well as considerable elucidation of the cdc25/wee1 regulatory pathways. Both cdc25 and wee1 appear to be regulated by upstream kinase/phosphatase networks. In addition, it is likely that other regulatory mechanisms cooperate with the wee1/cdc25 phosphorylation systems to control the action of cdc2. Together, these elaborate checks and balances ensure that cdc2 triggers mitosis at the appropriate time. PMID- 7880538 TI - Cell differentiation. PMID- 7880539 TI - Cell multiplication. PMID- 7880540 TI - Evidence for (PNA)2/DNA triplex structure upon binding of PNA to dsDNA by strand displacement. AB - The binding of PNA (peptide nucleic acid) T2CT2CT4-LysNH2 to the double-stranded DNA target 5'-A2GA2GA4 was studied by KMnO4 and dimethylsulfate (DMS) probing. It is found that upon sequence-specific strand displacement binding of the PNA to the dsDNA target concomitant protection of the N-7 of guanines within the target takes place. It is furthermore shown that the binding of this PNA is more efficient at pH 5.5 than at pH 6.5 and very inefficient at pH 7.5. These results clearly indicate that C+G Hoogsteen base pairing is present and important for binding and that the strand displacement complex therefore involves a PNA.DNA-PNA triplex. PMID- 7880541 TI - Electron microscopic studies of sequence-specific recognition of duplex DNA by different ligands. AB - The following ligands were used to study sequence specific recognition of duplex DNA by electron microscopic techniques: methyltransferases BspR1 and EcoR124 (recognition sequences GGCC and GAAN7RTCG, respectively), a biotinylated deoxyoligonucleotide 5'-CTCTCTCTCTCTCT-3' capable of forming triplex DNA, and PNA oligomer H-T10-LysNH2. For each ligand the best conditions for electron microscopic (EM) detection of stable specific complex formation were determined. It was demonstrated that EM allowed us to determine the position of the individual target site with an error of 15-20 bp, the relative affinities for individual target sites and kinetic parameters of the binding. These results open new possibilities for EM investigations of sequence-specific interactions with a wide range of other ligands of a similar nature. They also imply that a wide range of different sequences can be unambiguously and precisely mapped by EM and greatly extend the scope of EM applications for physical mapping of genomic DNA. PMID- 7880543 TI - Interaction of mithramycin with isolated GC and CG sites. AB - We have studied the interaction of the GC-specific, minor groove-binding ligand, mithramycin, with cloned DNA inserts containing isolated GC and CG sites flanked by regions of (AT)n and An.Tn using DNase I and hydroxyl radical footprinting. We find that mithramycin binds to GC better than CG and that AGCT is a better site than TGCA. Sites flanked by (AT)n appear to be bound better than those surrounded by An.Tn. Although no footprints are produced at T9GCA9 and T15CGA15, DNase I cleavage is enhanced within the GC sites suggesting that there is some interaction with the ligand. Mithramycin also alters the DNase I cleavage of (GA)n.(CT)n. PMID- 7880542 TI - Ethidium and azidoethidium oligonucleotide derivatives: synthesis, complementary complex formation and sequence-specific photomodification of the single-stranded and double-stranded target oligo- and polynucleotides. AB - Oligodeoxyribonucleotide derivatives containing ethidium or azidoethidium residues attached to 3' and/or 5' end were prepared. These derivatives formed tight specific complexes with complementary oligodeoxyribonucleotides where each attached ethidium residue led to an increase of complex Tm by 20-30 degrees C. Tandem complexes of two oligodeoxyribonucleotides containing ethidium residues with an oligodeoxyribonucleotide having two adjacent complementary sequences for these oligonucleotides were investigated. Photoinduced reactions of a number of ethidium and azidoethidium oligodeoxyribonucleotide derivatives with target complementary single-stranded and double-stranded oligo- and polydeoxyribonucleotides were investigated. The irradiation led to direct photocleavage of the target oligo- or polynucleotide, to formation of hidden (piperidine cleavable) modifications of the target and to formation of covalent adducts between ethidium oligodeoxyribonucleotide derivative and the target. In a number of experiments, azidoethidium dyes were demonstrated to be considerably stronger photosensitizers than ethidium ones. Depending on the nature of the target (single- or double-stranded DNA) and on the irradiation conditions, the total damages to the target oligo- or polydeoxyribonucleotides ranged from 10-70% (for ethidium dyes) to 30-80% (for azidoethidium dyes). PMID- 7880544 TI - Properties of RecA-oligonucleotide complexes. AB - The interaction of RecA protein with short single-stranded oligonucleotides is characterised by flow linear dichroism (LD), isoelectric focusing (IEF) and electron microscopy (EM). From LD and EM it is evident that RecA forms long filaments with at least some 50 oligonucleotides in a 'train formation'. The tendency to form trains is substantially lower when an amino group is attached to the 5' end of the oligonucleotide, suggesting that the modification impairs protein-protein interactions at the interface between two oligomers. From LD it is also evident that no bridging occurs between RecA-oligonucleotide complexes containing more than one oligomer strand per RecA filament. This property make them manageable in polyacrylamide gels, hence allowing characterisation by IEF. RecA was found acidic with a pI of 5.0. The pI was not dependent on the presence of bound cofactor (ATP gamma S) and oligonucleotides suggesting that protonation of the protein readily occurs to compensate for the negative charges provided by bound cofactor and DNA. PMID- 7880545 TI - Identification and analysis of a template-primer (ds-DNA) binding cleft in E. coli DNA polymerase I: an electrostatic potential contour pattern of the modeled structure. AB - In the modeled structure of the Klenow fragment of E. coli DNA polymerase I, we have identified a distinct region that exhibits a strong electropositive potential contour. The examination of the distribution of the electropositive and negative potential across the two-dimensional slices of the modeled structure revealed that the positive potential was concentrated around the cleft. The approximate size and shape of the region appears well suited to accommodate eight base pairs of duplex DNA and is consistent with the position of the dsDNA binding cleft reported in the crystal structure [Beese et al., Science (1993) 260, 352 355]. PMID- 7880546 TI - Synthetic alpha-helical peptides incorporating intercalators for DNA recognition. AB - The design and synthesis of a water-soluble 14-residue peptide, in which a quinoline intercalator is attached to the peptide backbone via alkylation of a central cysteine residue, is reported. 600 MHz 1H NMR spectroscopy and circular dichroism indicate that the peptide forms a nascent helix in aqueous solution, ie. an ensemble of turn-like structures over several adjacent residues in the peptide. A large number of sequential dNN(i, i+1) connectivities were observed in NOESY spectra, and titration of trifluoroethanol into a solution of the peptide resulted in the characteristic CD spectrum expected for an alpha-helix. At low DNA concentrations, CD spectroscopy indicates that this helical conformation is stabilized, presumably due to folding of the peptide in the major groove of DNA. PMID- 7880547 TI - The cofactor ATP in DNA-RecA complexes is not intercalated between DNA bases. AB - In an attempt to understand the role of ATP as a cofactor at the interaction of the RecA protein with DNA, we have studied the orientation geometries of the cofactor analogs adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) and guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) in RecA-DNA complexes using flow linear dichroism spectroscopy. Both cofactors promote the formation of RecA-DNA complexes of similar structure as judged from similar orientations of DNA bases. The DNA orientation was probed through the dichroism of the long-wavelength absorption of a DNA analog, poly(d epsilon A). In this way differences between the dichroic spectra of the ATP gamma S-RecA-DNA and GTP gamma S-RecA-DNA complexes, observed in the shorter-wavelength region, are related to orientation at variations of the cofactor chromophores. The results show that the guanine plane of GTP gamma S is oriented parallel with the principal axis of the complex in contrast to the more perpendicular orientation of the DNA bases. This observation directly excludes the possibility that the cofactor could be intercalated between the DNA bases. The orientation of the adenine base of ATP gamma S, which may be similar to that of guanine of GTP gamma S albeit not exactly the same, is also inconsistent with intercalation. The possibility that the cofactor bound to the protein could be intercalated in DNA had been speculated from the observation that some DNA intercalators can induce RecA binding to DNA in the absence of cofactor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880548 TI - Conformational properties of topoisomerase II inhibitors and sequence specificity of DNA cleavage. AB - The sequence specificity of topoisomerase-II-mediated DNA cleavage, stimulated by 2-methyl-9-hydroxy ellipticinium and 4',5,7-trihydroxyflavone (genistein) was investigated by sequencing analysis of DNA cleavage sites and molecular modeling techniques. The former drug exhibits a marked preference for a T base at the position immediately preceding the cleavage site (-1). The latter shares the preference for the same base, with an additional preference for a thymine at position +1. The cleavage intensity patterns in the presence of the two drugs differ considerably. From a conformational point of view, ellipticinium and genistein exhibit similar overall shape and dimensions. However, the fused ring system in the former generates a planar structure whereas the single bond, connecting the two aromatic portions in the latter, allows internal rotation. The most stable conformation of genistein corresponds to a deviation of about 40 degrees from planarity. A computer-assisted analysis was carried out to compare the steric and electrostatic properties of the two compounds. Two types of preferred (energetically almost degenerate) alignment for the two molecules were found. One corresponds to overlapping of the 9-hydroxyl containing ring of ellipticinium with the 4'-hydroxyphenyl moiety of genistein, the other envisages the same moiety of ellipticine superimposed to the hydroxyl-benzopyrone portion of genistein. The structural similarities of the test drugs might account for the common preference for stimulation of DNA cleavage at position +1, whereas the different possible arrangements of genistein in the cleavable complex could explain both the additional +1 specificity exhibited by this compound and the differences in cleavage intensity patterns observed in comparison to ellipticinium. PMID- 7880549 TI - Long-range interactions between DNA-bound ligands. AB - We have studied the interaction of the A:T specific minor-groove binding ligand 4',6-diamidino-2-phenylindole (DAPI) with synthetic DNA oligomers containing specific binding sites in order to investigate possible long-range interactions between bound ligands. We find that DAPI binds cooperatively to the oligomers. The degree of cooperativity increases with increasing number of binding sites and decreases with the separation between them. This dependence is paralleled by changes in the induced circular dichroism spectrum of DAPI, which decreases in intensity at 335 nm and increases at 365 nm. These results are consistent with an allosteric interaction of DAPI with DNA, where bound ligands cooperatively alter the structure of the DNA molecule. This structural change seems possible to induce under various conditions, including physiological. One consequence of allosteric binding is that ligands bound at a distance from each other sense each other's presence and influence each others' properties. If some regulatory proteins induce the same conformational change as DAPI, novel mechanisms for controlling gene expression can be anticipated. PMID- 7880550 TI - Effectiveness of the California 1990-1991 tobacco education media campaign. AB - The California Department of Health Services conducted a $28,600,000 tobacco education media campaign in 1990 and 1991. An independent evaluation of the media campaign featured four waves of data-gathering, one prior to the campaign's beginning and three at intervals thereafter. In all, 29,264 students in grades 4 12 and 6,785 adult smokers provided data for the evaluation. Through telephone interviews for adults and written questionnaires for students, these participants supplied information so that each person could be classified as exposed or unexposed to the media campaign's advertisements. Five criterion variables were used in the evaluation: campaign awareness, tobacco use, smokers' intention to quit, nonsmokers' intention to start, and attitudes toward smoking. Based chiefly on the differences between the results of waves 1 and 4, we believe the media campaign had a number of positive effects on California students. For adult smokers, the results were mixed. PMID- 7880551 TI - Characteristics of smokers who attempt to quit and of those who recently succeeded. AB - Although a high percentage of smokers attempt to quit each year, success rates are low. Thus, public health strategies must not only convince some smokers to attempt cessation, but also improve the success rate among other smokers already motivated to quit. Specific cessation strategies may be required for smokers in these two groups. This study compares sociodemographic and health behavior characteristics of smokers who have and have not attempted to quit and of those who recently succeeded. To determine whether these characteristics vary for men and women, we stratified analyses on gender. Data were obtained from random sample health surveys conducted 1981-1982 and 1983-1984 in two New England communities. Analyses include data on 2,086 respondents who reported smoking cigarettes in the previous year. Men and women were equally likely both to attempt cessation and to quit. Except for an inverse association with age, attempting to quit was not associated with sociodemographic variables. In men and women, attempts were associated with encouraging others to quit and attempting to increase exercise. Successful cessation attempts were associated with not living with a smoker in women; marital status, attempted weight loss, and increased age in men; and with efforts to increase exercise in both men and women. These characteristics could be useful in targeting smokers who attempt to quit, but fail. Improving the success rate in this group could greatly reduce smoking prevalence in the community. PMID- 7880552 TI - History of smoking from the Washington State death certificate. AB - Beginning in 1988, a question added to the Washington State death certificate asked whether the decedent had smoked during the last 15 years of life. We analyzed death certificate data to evaluate the effectiveness of this question in identifying groups with high smoking rates and occupations with high rates of respiratory disease death among nonsmokers. We obtained statistical death certificate data from the Washington State Department of Health for resident deaths occurring between 1988 and 1991. Analyses included information on age, sex, race/ethnicity, marital status, underlying cause of death, high school graduation, smoking during the last 15 years of life, and occupation. Based on logistic regression analysis, we found that male sex, youth, divorced status, or death from lung cancer, chronic obstructive lung disease, or ischemic heart disease predicted a higher risk of smoking during the last 15 years of life. Hispanic ethnicity, single or widowed status, high school graduation, or death from breast cancer, diabetes, motor vehicle accidents, other accidents, or homicide predicted a lower risk of smoking. In farming occupations, there was an excess number of chronic obstructive lung disease deaths among nonsmokers. Findings from this study suggest that patterns of smoking during the last 15 years of life among decedents can provide useful public health surveillance information. The collection of risk factor information, such as smoking, should be recommended for the U.S. standard death certificate. Questions on smoking should be both simple and answerable by informants who may not have known the decedent for a lifetime. Additional studies on the accuracy of smoking history from the death certificate should be conducted. PMID- 7880553 TI - Effects of a community intervention to change smoking behavior among Hispanics. AB - Our purpose was to evaluate the effects of the Program Latino para Dejar de Fumar (PLDF), a community-wide smoking cessation intervention developed for Spanish speaking Hispanics. PLDF community intervention was based on research to identify culture-specific aspects of smoking cessation for Hispanics and included targeted distribution of a self-help cessation guide, an electronic and printed media campaign, raffles for smokers who quit, and participation in community activities. The main outcome measures were smoking cessation and associated behaviors. Exposure to the intervention, the primary predictor variable, was defined as affirmative responses to questions about recognizing the PLDF name, having the PLDF smoking cessation guide, having heard or seen messages about PLDF on various media, and knowing about a PLDF-sponsored $500 raffle. Four cross sectional telephone surveys of Hispanic adults 18 to 65 years of age, living in neighborhoods in San Francisco, California, defined as having at least 10% Hispanics in the 1980 U.S. Census, were conducted preceding (1986-1987) and following (1988-1989) start of PLDF (total n = 7,667). Although smoking prevalence decreased over the four years, smoking cessation in the 12 months prior to the survey was unrelated to exposure to PLDF. For the two surveys conducted after PLDF was started (n = 3,551), nonsmokers, women, older adults, and less acculturated persons were more likely to report exposure to PLDF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880554 TI - Use of a clinician reminder system for screening mammography in a public health clinic. AB - Physician reminder systems have been used to increase the appropriate use of clinical preventive services. These systems, though, have been typically tested in resident clinics. We conducted this study, using a time-series design, to determine if a manual clinician reminder system could increase the use of screening mammography in an urban public health clinic. In the one-year baseline period, 47% of women who were due for a mammogram received the procedure; the corresponding percentage in the one-year intervention period was 72% (P < .0000001). The improvement reflected a large increase in appropriate ordering behavior by primary care providers rather than an increase in patient adherence. This study demonstrates that a noncomputerized reminder system can greatly improve the delivery of screening mammography in a public health clinic setting. PMID- 7880555 TI - Facility-based inreach strategies to promote annual mammograms. AB - Mammography facilities frequently use inreach strategies, such as reminders, to encourage annual returns by asymptomatic women 50 years of age and older. We describe three pilot studies that systematically compared various strategies. In each study, patients seen for a screening mammogram during a specified period were randomly assigned to a novel reminder condition or a comparison condition one year later, and return rates were monitored. In study 1, return rates for subjects receiving a standard mailed reminder (36%) and subjects receiving a mailed reminder plus incentive (32%) were similar. In study 2, return rates for subjects receiving a mailed reminder (44%) and subjects receiving a phoned reminder (48%) also were similar. However, study 3 focused on a mailed reminder on the referring physician's letterhead sent by the mammography facility versus no reminder, and a significant increase in return rates resulted (47% versus 19%). We present the implications of this pattern of findings and discuss the need for a larger trial of the physician-endorsed reminder. PMID- 7880556 TI - Physicians' awareness of mammography charges. AB - Although physicians commonly report cost as a barrier to screening mammography, their awareness of mammography charges is unknown. Using a statewide sample, we assessed accuracy of primary care physicians' estimates of mammography charges among 506 eligible physicians who returned questionnaires. Differences between estimated charges and actual charges at their mammography referral facilities were small (mean = $2.74, median = 0) and unrelated to physicians' specialty, age, gender, or practice type. We conclude that physicians are cognizant of mammography charges. Overestimates in charges may not explain low mammographic screening rates. PMID- 7880557 TI - Personal contact from friends to increase mammography usage. AB - To increase the use of mammography among women 40 years of age and older, the American Cancer Society (ACS) designed a telephone intervention strategy (the "Tell A Friend" program) that relied on ACS volunteers. During a half-day training session, each volunteer provided a list of 10 women she was willing to contact over a 6-month period and encourage to have a mammogram. Each list was randomized, and five names were returned to each volunteer for inclusion in the intervention. The other women served as controls and were not contacted by the volunteers. All women were subsequently interviewed at the end of the intervention period. Forty-nine percent of the women in the intervention group (n = 289) had received their most recent mammogram since the start of the intervention period, whereas 34% of control women (n = 305) received mammograms during the same time period (p < or = .001, rate ratio = 1.4, 95% confidence interval = 1.2, 1.7). The effectiveness of the intervention remained after controlling for demographic characteristics. The strategy was effective for both black and white women of all ages, but principally among women with annual household incomes of less than $40,000. We conclude that a telephone intervention strategy of personal contacts between acquainted women can significantly increase mammography use, particularly among women with low-to-moderate income. PMID- 7880558 TI - Physician advice to reduce chronic disease risk factors. AB - The U.S. Preventive Services Task Force recommends that physicians advise their patients regarding smoking cessation, weight loss, and physical inactivity. Few studies, however, have assessed the extent to which persons with these risk factors receive advice from their physicians. Using data from the 1990-1991 Missouri Behavioral Risk Factor Surveillance System (BRFSS), a random digit dialed telephone survey of adults, we identified Missouri residents with one or more of these modifiable risk factors. We examined whether these persons reported being advised by their physicians to modify their behavior(s) within the past year. Of the 2,791 respondents, 764 (26%) smoked, 1,720 (59%) were sedentary, and 686 (23%) were overweight. Five hundred and thirty-five smokers reported having a routine checkup within the past year, but only 224 (42%) reported being advised by their physicians to stop smoking. Of the 1,246 sedentary persons who had a routine checkup within the past year, 192 (15%) reported being told by their physicians to exercise more. Of the 521 overweight respondents who had a routine checkup within the past year, 225 (43%) reported being advised to lose weight. Physician advice for these risk factors was less frequently reported among men, blacks, younger persons, and persons from rural areas. Although most Missouri residents with these modifiable risk factors reported seeing their physicians within the past year, less than half reported that they received advice from their physicians to alter their risk behavior(s). Further efforts are necessary to increase the effectiveness of physician advice for at-risk patients about quitting smoking, losing weight, and increasing physical activity. PMID- 7880559 TI - Percutaneous injuries on the "front line": a survey of housestaff and nurses. AB - Our objective was to assess the frequency of work-related percutaneous injuries in two high-risk groups and to compare patterns of injury and reporting in these groups. Data were collected through an anonymous, self-administered survey distributed to all full-time nurses and housestaff. The survey results were compared to Employee Health Service records. Surveys were returned by 258 of 330 housestaff and 455 of 593 nurses for a response rate of 77% (housestaff = 78%; nurses = 76%). The respondents were highly representative of the nursing divisions and residency programs surveyed. The percentage of nurses who had ever sustained percutaneous injuries was 64.7%; for housestaff it was 74.1% (prevalence difference = -9.4%, 95% confidence interval [CI] = -16.4%, -2.4%). The percentage of nurses who had sustained recent injuries was 34.6%; for housestaff it was 43.0% (prevalence difference = -8.4%, 95% CI = -15.9%, -0.9%). Injuries with syringe needles were the most common, followed by injuries with suture needles, scalpels, and then a variety of other sharp objects and instruments. The nurses were more likely to seek care as directed by hospital policy at the Employee Health Service (reporting difference = 29.7%, 95% CI = 19.5%, 39.9%) or the Emergency Room (reporting difference = 11.9%, 95% CI = 8.1%, 20.0%). Knowledge of policy increased the probability of reporting by nurses. The housestaff were more likely to evaluate injuries themselves (reporting difference = -16.7%, 95% CI = -26.8%, -6.6%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880560 TI - The promise of advertising and media advocacy for tobacco control. PMID- 7880561 TI - The calvarium. AB - The calvarium is a crucial structure that can manifest a great deal of pathology. The plain film remains the main imaging modality, although CT and MRI are becoming increasingly important. We discuss its anatomy, normal variants, congenital and developmental anomalies, hematologic disease, idiopathic disorders, neoplasms, metabolic disease, trauma, and the postoperative skull. Whenever possible, we emphasize CT and MRI. PMID- 7880562 TI - The cranial meninges: anatomic considerations. AB - The anatomy of the cranial dura and leptomeninges is both intricate and complex. A thorough discussion of the protective covering of the brain including the dura, arachnoid, and pia is provided on both gross and microscopic levels. An attempt to include issues of clinical relevance is made, highlighting the Virchow-Robin spaces and the optic sheath. In addition, the normal appearance of the dura and leptomeninges on MRI is presented to establish a framework for the discussion of leptomeningeal pathology. PMID- 7880563 TI - Neuroimaging of meningeal disease. AB - In the past two decades, the advent of CT and MRI has made a considerable impact on the evaluation of meningeal diseases, conditions once regulated to cytological, histopathological, or postmortem analyses alone. This article reviews the imaging findings in various meningeal processes with particular attention to the anatomic definition of the meningeal layers and their relationship to the development of meningeal pathology and consequent imaging characteristics. PMID- 7880564 TI - Normal and variant anatomy of the dural venous sinuses. AB - The normal and variant anatomy of the cerebral veins and dural venous sinuses is poorly understood by many radiologists. Beginning with a discussion of cerebral venous anatomy, this review illustrates clinically pertinent anatomy of the cerebral sinovenous system. Various methods of imaging cerebral veins and dural venous sinuses are described. Techniques and pitfalls of MR venography are emphasized. PMID- 7880565 TI - Congenital and acquired abnormalities of the dural venous sinuses. AB - The imaging features of a variety of dural venous sinus (DVS) abnormalities are reviewed. Congenital and heritable diseases affecting the DVS, tumor-related sinus compression, and traumatic injuries of the DVS are discussed. The causes, clinical manifestations, and imaging findings in cerebral sinovenous thrombosis are described, and pertinent imaging techniques and pitfalls are illustrated. Etiologic theories about the formation of dural arteriovenous malformations are discussed and their imaging features are demonstrated. PMID- 7880566 TI - Tomorrow's doctors. PMID- 7880567 TI - Voices of leadership in a community under stress: personal observations by officials on an epidemiologic mistake. AB - We studied the responses of leaders in a suburban community in western Canada near Edmonton, Alberta, that was affected by a false allegation of increased cancer risk. In 1986, a cancer agency responded to community concerns by conducting a study of cancer incidence (1979-1983) and reported elevations on the order of 25 per cent over expected for most sites. Reanalysis of these data several months later revealed an error in the population figure used to calculate the rates. Correction brought the rates into line with Alberta as a whole and comparable to those for other communities surrounding Edmonton. We interviewed elected and appointed public officials in one affected community as well as non official community leaders and realtors to determine their subjective impression regarding the effect of the incident on their communities and to rule out alternative explanations for the drop in housing prices in association with the incident we have reported elsewhere. Their narrative responses were particularly interesting and articulate, and are quoted at length. Their collective perceptions appear to confirm the impression of a profound impact on the community, reflected in housing prices, and attribute at least part of the impact to the disclosure that a high official in the community was afflicted by cancer. Most felt that there remained a great deal of latent concern in the community and at least some felt that a subsequent public issue involving transmission line rights-of-way near the community reactivated this latent concern. PMID- 7880568 TI - Public health has no place in undergraduate medical education. AB - It is time to review the reasons for including public health in medical education. Undergraduate medical students are interested above all in the diagnosis and treatment of individual cases of disease; population-based health care means little to most students, and is seldom regarded as important. Should public health teachers concentrate their efforts in other areas, where students are more receptive? This paper presents arguments for and against the proposition that public health has no place in the undergraduate medical course. In favour of the proposition, it is argued that the clinical imperative is so firmly entrenched in the minds of students and in the cultures of medical schools that public health will always be diminished and elbowed to one side in medical curricula. Moreover, the major gains in the health of populations will be won in other arenas. Therefore public health should rupture the links with medical schools that were formed in another age and, in any event, are now weakening as public health strikes a new identity. The effort that currently goes into teaching unwilling medical students would have better returns if it was invested elsewhere. Against the proposition, it is argued that the health of populations will not be improved without participation of all groups with an interest in and an influence on health care. No group is more influential in the organization and delivery of health services than the medical profession, so it would be foolish for public health to withdraw from medical education. Moreover, effective medical practice requires an ability to think in terms of populations as well as individuals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880569 TI - Thresholds for treatment in cataract surgery. AB - BACKGROUND: The aim of the study was to identify the criteria used by ophthalmologists when assessing patients who may require cataract surgery, examine the extent of variation in their application and explore their relationship with current patterns of supply and demand. METHODS: This was a descriptive study involving semi-structured interviews with ophthalmologists, examination of hospital clinical records, and analysis of routinely available data on waiting times and hospital activity. The setting was ophthalmology units within the Northern Region of England. The subjects were 27 consultant ophthalmologists and 160 patients undergoing cataract extraction. RESULTS: There was agreement amongst ophthalmologists on the criteria used to select patients for treatment, and on the visual acuity level at which they would usually recommend surgery. All assess the degree of handicap resulting from cataract; most consider this more important than visual acuity. Over half of the patients were over 75 years old; two-thirds were women. Median visual acuity at listing was 6/36, but over 40 per cent were 6/60 or worse. Visual acuity at treatment was not recorded for 32 per cent of patients. Wide variation in visual acuity at listing existed between both units and consultants, and for both the affected and other eye. Second extractions may be performed at a better level of visual acuity than for first extractions. Median visual acuity at listing was significantly correlated with total waiting times for individual consultants. Lower cataract extraction rates are associated with long waiting times and poorer visual acuity at listing. CONCLUSIONS: There is considerable unmet need for cataract treatment within the Northern Region and significant variation in the current meeting of needs and demands. It may be that more needs could be met simply by changing referral and treatment patterns without increasing total service activity. Although visual acuity is a reasonably objective measure in routine use, the level of visual handicap is more important, and its assessment is more subjective; development of a standard method to assess this could help in producing guidelines for patient referral and selection. Audit of treatment thresholds could allow a better matching of service provision to population needs. PMID- 7880570 TI - Methods of establishing criteria for purchasing coronary angiography in the investigation of chest pain. AB - BACKGROUND: Purchasers may now define how many clinical procedures they wish to buy. In the investigation of chest pain, coronary angiography provides a definitive diagnosis. In clinical practice, the use of coronary angiography varies, so purchasers may choose the sort of service they wish to buy. We reviewed the extent of variation in the investigation of patients in the Trent Region and present a system for establishing criteria for the purchase of coronary angiography. METHODS: Three studies are presented, based on patients referred to the three referral centres in the Trent Region. First, the appropriateness for investigation, defined as benefit outweighing risk, is determined by expert panel; second, an audit of patients referred for coronary angiography is presented; and third, the likelihood or probability of significant coronary disease is assessed by application of a logistic regression model. RESULTS: According to the panel criteria, 27 per cent of patients in one centre were judged inappropriate for coronary angiography, 28 per cent in the second centre and 10 per cent in the third. When referred for angiography, extent of anti-anginal medication, symptom severity, use of exercise testing, and result of and planned management after angiography varied widely among centres. The likelihood of significant coronary artery disease could be predicted in 86 per cent of patients. CONCLUSIONS: Variation in clinical practice does not make the purchasers' task easy. Based upon these studies and clinical trials of coronary artery bypass surgery and coronary angioplasty, we present potential performance indicators which may form the basis of contracts or be used as audit measures. PMID- 7880571 TI - Attaining The Health of the Nation targets for ischaemic heart disease: the contribution of a clinical outcome measure. AB - BACKGROUND: Deaths occurring within 30 days of admission as a percentage of all admissions with acute myocardial infarction' was recently defined by the Scottish Office Clinical Resource and Audit Group as a clinical outcome measure for inclusion in service contracts between purchaser health authorities and provider NHS trusts. The aim of this study was to determine the extent to which improvements in the clinical outcome measure have already contributed and may continue to contribute to attaining the Health of the nation targets for ischaemic heart disease (IHD). METHODS: Information was obtained from the computerized discharge summaries of patients treated in Tayside hospitals and the death registrations provided by the Registrar General for Scotland. RESULTS: In Tayside between 1980-1982 and 1990-1992, the number of death outside hospital from acute myocardial infarction (AMI) in the under-65s fell by 33 per cent, and the proportion of patients admitted as emergencies with AMI who died within 30 days fell by 40 per cent. The proportion of diagnosed heart attacks which proved fatal fell by a third over the period. CONCLUSION: As 75 per cent of deaths from IHD in the under-75s still take place before hospital admission, not more than 25 per cent of the overall fall in deaths from IHD can be accounted for by improvements in the clinical outcome measure. Most of the fall was apparently unrelated to immediate medical intervention after an attack, long-term nutritional and behavioural changes possibly having reduce the severity of diagnosed attacks. The Health of the nation targets cannot therefore be met by improvements in the clinical outcome measure alone. PMID- 7880572 TI - Communicable disease control in England; recommendations from an American. AB - The problems associated with the Wakefield salmonella and the Stafford Legionnaires' disease outbreaks and the recommendations of the Acheson Committee formed in response led to the creation of the position of Consultant in Communicable Disease Control (CCDC) within the District Health Authorities. The reality of the position as implemented differs from that envisaged by the Acheson Committee and has resulted in ambiguities about the role of the CsCDC, the source of their support, and the range of their responsibilities. This paper, by an American invited to review the position, outlines the history of the position, the current status of CsCDC, and the barriers to effective performance of the position. It ends with a series of recommendations for improving disease control within England by solidifying the position, establishing its role in disease control within the National Health Service and recommending an educational/training pathway to attract and prepare physicians for the position. PMID- 7880573 TI - Reflections on the consanguinity and birth outcome debate. AB - The high rate of consanguineous marriages has been implicated as an important factor in the high rates of perinatal mortality and congenital malformations among the UK Pakistani population. This paper critically considers the debate on consanguinity and birth outcome. A critical review of epidemiological literature is placed in the context of wider, but centrally important, debates on social class and ethnic categorizations, notions of culture and literature on racism. The epidemiological literature is inconsistent in its findings, and is often based on data and arguments of dubious validity. Equally, notions of social class, ethnicity and culture used in such studies lack sophistication and require reconsideration. Health policy options based on promoting cultural change in marriage patterns, conveniently but unjustifiably, shift the blame of poor birth outcome onto the Pakistani community and are doomed to failure. The consanguinity hypothesis is over-simplistic to explain the higher rates of perinatal mortality and congenital malformations among the Pakistani population. Its popularity rests less on its scientific merit and more on its convenience in shifting the blame onto supposedly deviant cultures and marriage patterns and its fit with racist ideas of alienness and deviance. PMID- 7880574 TI - Constructing regions for small area analysis: material deprivation and colorectal cancer. AB - BACKGROUND: This paper is about constructing small areas for the analysis of health data with the aims of health service delivery in mind. The areal framework should enable the analyst to link health data and census data and the areas should have large enough populations to ensure that rates are reliable and be homogeneous with respect to important socio-economic attributes. METHODS: An information-based statistic is used for the construction of regions in Sheffield based on the Townsend deprivation index. Enumeration districts are used as the geographical building blocks for the regions. The new regional framework is used for computing Bayes adjusted standardized incidence rates for colorectal cancer (CRC) across Sheffield. The paper then examines the statistical relationship between CRC incidence and deprivation across the set of regions using bivariate regression. RESULTS: The method yields regions that are considerably more homogeneous in terms of deprivation than wards, and using this framework it is shown that there is a (weak) statistical association at the regional scale between deprivation and CRC. CONCLUSION: We conclude that statistical tools can be employed to provide regions that meet the criteria for small area analysis of health data and the analyst does not have to be tied to large administrative units such as wards. There are some benefits to executing this work within a Geographic Informative System. The method should be of interest to those concerned with health service delivery and the identification of 'problem regions'. PMID- 7880575 TI - Understanding differences between high and low childhood accident rate areas: the importance of qualitative data. AB - BACKGROUND: The research discussed in the paper was undertaken for a District Health Authority to aid the development of appropriate policies to achieve the Health of the nation strategic target for reducing the death rate from accidents amongst children under 15. There has been a great deal of quantitative and epidemiological research into childhood accidents which has demonstrated a clear social class gradient in childhood accidents, fatalities and injuries. Less research has been undertaken into the possible reasons for the 'social patterning' of accidents and other aspects of health. Recent sociological research on childhood accidents has adopted a more qualitative approach and studied childhood safety within a family and community context. This approach has been used in the Huddersfield study on parental perspectives on childhood safety. METHODS: In-depth interviews were held with a sample of parents from a high and a low childhood accident rate area. RESULTS: The two focus areas reveal contrasting social profiles. There were significant differences on a number of aspects of parental perceptions on safety and beliefs about accidents, in the two areas. Analysis of accident events revealed that all the families in the high childhood accident rate area sample had children who had had an accident in the past which required hospital treatment. A high proportion of their children had experienced 'near misses'. In contrast, half the families in the low childhood accident rate area had children who had experienced an accident in the past and a much smaller proportion had experienced 'near misses'. All the parents in the sample from both areas developed rules, routines and practices to keep their children safe. The study suggests that there are social class differences in the effective use of these safety rules. CONCLUSION: Qualitatively orientated sociological research into parental perspectives on childhood safety contributes to an understanding of the reasons for the social patterning of childhood accidents. Such information should be of help to professionals in their prevention and safety promotion work. PMID- 7880576 TI - A taxonomy of shared care for chronic disease. AB - BACKGROUND: Shared care is promoted as a way of integrating primary and secondary services and achieving one of the targets set for the NHS in the 1990s. We aimed to compose a taxonomy of shared care schemes for chronic disease in order to inform the development of develop shared care. METHODS: A two-phase postal questionnaire survey of Scotland and North West Thames Region, England. In the first phase we identified the number of shared care schemes for chronic disease, which were followed up in the second phase. RESULTS: Shared care schemes were classified into six groups, or models, according to their method of data transfer. These are: (I) community clinics, where the specialist undertakes a clinic in general practice; (II) basic, where communication comprises the regular exchange of letters or standardized record sheets; (III) liaison, where the hospital team and general practitioner (GP) meet to discuss and agree the management of patients under shared care; (IV) shared care record cards, where the exchange of information is made through a booklet or 'cooperation card', commonly carried by the patient; (V) computer-assisted shared care, where a circuit of information is established between GP and hospital specialist based on data collected at each patient visit and mediated through computer-generated summaries; (VI) electronic mail, where hospital specialist and GP both have access to the same data on patients shared between them. CONCLUSION: Despite substantial variation in the operation of shared care, schemes can be broadly classified and constructed in six different ways. In establishing this taxonomy, a choice is offered to health care workers wishing to develop shared care. PMID- 7880577 TI - A randomized trial of immediate discharge of surgical patients to general practice. AB - BACKGROUND: This study compares, in clinical and economic terms, out-patient follow-up with immediate discharge to general practice of patients undergoing any one of 29 defined surgical procedures. METHODS: A randomized controlled trial was undertaken in which patients recruited from two general surgery wards in Ninewells Hospital, Dundee, were randomized to follow-up care in the out-patient clinic or in general practice. Outcome was measured as clinical effectiveness in terms of morbidity and mortality; economic costs to the hospital compared with general practice; patient benefits and satisfaction; and General Practitioners' (GPs') opinions of the system. RESULTS: A total of 455 patients were randomized to outpatient and 454 to general practice follow-up. They were followed up for a minimum of six months. There were no differences in readmission rates, mean number of operations or mortality. The difference between the groups in the total health service costs was very small (2.68 pounds per patient more for those receiving out-patient follow-up). More of the general practice group preferred general practice care than the out-patient group preferred out-patient care (p = 0.03). The patient's travel costs and travel and treatment time were greater for the out-patient group (27.99 pounds, 113 min) than for the general practice group (24.90 pounds, 82 min). The GPs felt they had been given adequate information in the discharge documentation and were willing to accept immediate discharge as normal policy, although they expected it to increase their workload. If immediate discharge were instituted, the time saved in an out-patient clinic session of 40 patients would be an estimated 54 minutes, enough to see three extra new patients. CONCLUSION: General practice based follow-up care for this group of patients is as effective as, but less costly than outpatient care and is acceptable to GPs. Because of only small differences in costs between the two forms of follow-up, real gains to the health service will depend on the use of the time freed by a reduction in follow-up appointments in the out-patient clinic. PMID- 7880578 TI - Radon and health--an update. AB - BACKGROUND: The National Radiological Protection Board (NRPB) estimated in 1990 that radon causes 5 per cent of lung cancer in the United Kingdom. The estimate was not based on direct evidence. Since then a number of epidemiological studies have been reported. In addition, various policies have been formulated and some implemented, including the mounting of public campaigns to reduce radon in houses in parts of the United Kingdom. METHODS: A review of the scientific literature, policy documents and results of the campaigns has been undertaken. RESULTS: New data on miners support previous evidence that radon, at the levels found in mines, does cause lung cancer. The one study to add to the two previous case control studies looking at domestic radon tips the scales slightly towards radon being incriminated in homes as well. The effect of smoking, a multiplicative or additive risk with radon, is still unclear. Radon can be calculated to cause up to 383 lung cancer deaths per year in the five currently designated 'radon affected' areas. Approximately 287 of these deaths will be in cigarette smokers, and the most effective way for smokers exposed to radon to reduce their lung cancer risk is to stop smoking. CONCLUSION: Evidence of the risk from residential radon is still insufficient to justify the current NRPB advice. If it were, a much more effective radon campaign would be needed. Such a campaign would concentrate on reducing lung cancer in people by tackling both radon exposure and cigarette smoking, rather than simply reducing radon in houses. PMID- 7880580 TI - Quarterly communicable disease review April to June 1994. From the PHLS Communicable Disease Surveillance Centre. PMID- 7880579 TI - Stressful life events and psychiatric disturbance in junior school children. AB - BACKGROUND: Stressful life events have been implicated in the aetiology of childhood psychiatric disorders. Previously, the measurement of life events and exploration into the social origins of childhood psychopathology has predominantly utilized clinic samples and parental information. METHODS: A population-based study was performed to measure experienced stressful life events and the levels of psychiatric disturbance in 8-11-year-old children. Essentially, the project consisted of two stages. First, using an adapted life events questionnaire, 352 children were initially screened to identify two extreme groups: 30 high and 30 low life event scorers. Second, these identified children subsequently completed a detailed life events interview and the questionnaire was re-administered. Additionally, for each child, responses to a parent version of the life events questionnaire were obtained and three measures of psychiatric disturbance were made. RESULTS: The child life events questionnaire had reasonable overall test-retest reliability (r = 0.650); although differential reliability between the individual items was found. Employing the parent version as the criterion, it was established that the questionnaire had fairly good concurrent validity (sensitivity 79 per cent, specificity 73 per cent). Higher levels of psychiatric disturbance were discovered in the group of high life event scorers; that is, in those children who had experienced a greater number of major stressful life events. CONCLUSION: The developed child life events questionnaire is a beneficial screening instrument for use in community populations. Future investigations into the aetiological role of life events may assist in the prevention of childhood psychiatric morbidity. PMID- 7880581 TI - School language surveys: an underused source of data. PMID- 7880582 TI - Is antenatal care apportioned according to obstetric risk? PMID- 7880583 TI - Unsettling times for public health. PMID- 7880585 TI - Eggs, recipes and Salmonella food poisoning. PMID- 7880584 TI - Unsettling times for public health--another view. PMID- 7880586 TI - Motor axon terminal regeneration as studied by protein gene product 9.5 immunohistochemistry in the rat. AB - Normal intact and regenerating axon terminals up to 30 days after nerve crushing were studied in the rat flexor carpi ulnaris muscle by confocal laser scanning microscopy (CLSM) and electron microscopy using immunohistochemistry for protein gene product 9.5 (PGP 9.5). The motor axons were intensely and homogeneously stained along their entire length. "Three dimensional" organizations of elaborate axon terminals were clearly demonstrated by reconstructing serial optical images obtained by CLSM in normal neuromuscular junctions. In the injured nerve, the earliest regenerating axons could be identified at endplate regions six days after nerve crushing as intensely immunoreactive thin processes which bifurcated in T-shape and formed delicate lace-like terminals. Such lace-like terminals were composed of fine thread-like portions 0.2-0.8 microm in diameter and expanded portions of 2-3 microm in diameter. Electron microscopy revealed that all the axon terminals in the cytoplasm were stained almost homogeneously by PGP 9.5 immunohistochemistry up to their extreme tips. Axon terminals were in direct contact with the basal lamina of the postsynaptic folds, and showed occasional branching. The thin thread-like portions contained no mitochondria but only a few vesicles, where as the expanded portions, abundant mitochondria. And preterminal axons and some expanded portions were abutted by Schwann cells, while thin thread like portions were exposed with no association with Schwann cells. Twenty to 30 days after crushing injury, regenerating motor axon terminals resumed their mature form in terms of branching elaborations and ultrastructural features. Thus, CLSM of PGP 9.5 immunocytochemistry combined with electron microscopy was able to demonstrate the "three-dimensional" organization of elaborate axon terminals at high resolution in the normal and regenerating neuromuscular junctions. Using this technique, extremely fine processes of axonal terminals were identifiable at the earliest stage of reinnervation. PMID- 7880587 TI - Cytoarchitecture of periendothelial cells in human cerebral venous vessels as compared with the scalp vein. A scanning electron microscopic study. AB - Three-dimensional cytoarchitectures of the periendothelial cells of human cerebral venous vessels as well as a scalp vein were studied by scanning electron microscopy after removal of extra-cellular connective tissue matrices with a KOH collagenase digestion method. Postcapillary venules appeared covered with pericytes, while collecting venules had stellate periendothelial cells which formed a basket-like network around the vessel wall. As the size of the venous vessels increased, the stellate periendothelial cells became flat in shape and dense in arrangement. Although they had some characteristics similar to the smooth muscle cells in surface structure, no spindle-shaped smooth muscle cells were recognizable even in the superficial cerebral veins. On the other hand, the scalp vein was densely covered with spindle-shaped smooth muscle cells running circularly. These findings suggest that the cerebral venous vessels cannot constrict strongly as compared with the scalp vein, but probably regulate blood volume by mildly changing the caliber of the vessels. PMID- 7880588 TI - Scanning electron microscopic studies of the medial smooth muscles in human major intracranial arteries. AB - The three-dimensional arrangement of the medial smooth muscle cells of human major intracranial arteries was studied by scanning electron microscopy after removal of extracellular connective tissue matrices with a KOH-collagenase digestion method. In the straight portion of the major arteries, the smooth muscle cells were arranged roughly circularly, whereas the arrangement was somewhat random in the vertebral, basilar, and internal carotid arteries. Groups of the longitudinal muscle cells were also found in the vertebral, basilar, and internal carotid arteries, but were absent in the anterior, middle, and posterior cerebral arteries. At a higher magnification, smooth muscle cells in these arteries formed anastomosed bundles about 5-30 micrograms in diameter. The smooth muscle cells in the dichotomous branching and the uniting portions were arranged circularly, but multidirectionally and longitudinally oriented smooth muscle cell groups were present in the facial and dorsal walls of the forked vessels. These multidirectional muscle cell groups were small in number in the portion where the major arteries gave off lateral branches at a right angle. So called "medial defects" were found at the crotch of the bifurcating region in two cases out of four. Smooth muscle cells near the defects tapered off toward the center of the defect where internal elastic lamina with oval fenestrations were exposed. However, no special arrangement of the smooth muscle cells was observed around the "medial defects" as compared with that in the ordinary bifurcating region. PMID- 7880589 TI - Non-specific cytotoxic response against tumor target cells mediated by leucocytes from seawater teleosts, Sparus aurata and Dicentrarchus labrax: an ultrastructural study. AB - The in vitro cytotoxic reaction of leucocytes from the seawater teleosts gilthead seabream (Sparus aurata) and sea bass (Dicentrarchus labrax) against tumor target cells was studied by transmission and scanning electron microscopy. Head-kidney, blood or peritoneal exudate leucocytes were incubated with HeLa or B16 melanoma cells. After incubation, conjugates of leucocytes (effectors) and tumor cells (targets) were observed. Both the effector-target cell binding and target cell lysis steps of the cytotoxic process were characterized. Usually more than one effector was bound to the same target. The effectors exhibited ultrastructural features of either monocyte or lymphocyte cells. Monocyte-like effectors possessed an oval or kidney-shaped heterochromatinic nucleus and a few granules. They were flattened against the targets over a broad area or, occasionally, made several punctuated contacts. Lymphocyte-like effectors had a large, rounded or indented nucleus, numerous free ribosomes and occasional cytoplasmic granules. These effectors established spot contacts with the target. Contacts between monocyte-like and lymphocyte-like effectors were also recognizable. After incubation, some targets appeared virtually intact, while others had a smooth surface or showed cell processes and surface blebs. These ultrastructural changes in the targets are similar to those described as mediated by mammalian cytotoxic cells. PMID- 7880590 TI - Immunohistochemical distribution of 7B2 and colocalization with calcitonin gene related peptide in rat lung. AB - The novel pituitary protein 7B2 has a widespread distribution in neurons and paraneurons and is known to be associated with endocrine disorders. In the mammalian lung, solitary neuroendocrine cells (NECs) and their innervated aggregates, termed neuroepithelial bodies (NEBs), are scattered along the bronchopulmonary tree; however, presence of 7B2 in these structures has not previously been reported. Bouin fixed, paraffin embedded rat lungs were cut and stained for 7B2, using a polyclonal antibody and a streptavidin biotin immunoperoxidase method. The identity of NEBs was confirmed on adjacent serial sections by the immunocytochemical reaction for calcitonin gene-related peptide (CGRP). NEBs selectively labelled for 7B2 are distributed throughout bronchi, bronchioli and alveolar ducts, whereas NECs are always negative. Likewise, 7B2 immunoreactivity is not detected in intrapulmonary ganglion cells nor in nerve fibers. Immunoreactivity for CGRP, on the other hand, occurs in NECs, NEBs, nerve fibers and neuronal somata. Colocalization of both peptides is demonstrated in almost all NEBs. This study presents the first immunohistochemical demonstration and morphological mapping of 7B2 in the rat lung. The finding that only NEBs are stained suggests biochemical and functional variations between NEBs and NECs as well as the absence of a role for 7B2 in the pulmonary nervous system. PMID- 7880591 TI - Oocyte follicle cells association during development of human ovarian follicle. A study by high resolution scanning and transmission electron microscopy. AB - Morphodynamics of oocyte follicle cells association during the development of human ovarian follicles were studied by transmission electron microscopy and high resolution scanning electron microscopy including the ODO method. For this study primordial, primary, growing preantral and antral follicles were systematically analysed in a total of 20 adult and fetal (3-8 months and at term) ovaries. In early stages of follicle development (primordial and primary stages) the flattened and/or polyhedral cells, closely associated with the growing oocyte, project an increasing number of microvillous processes. These are in apposition with the oolemma, and form bulbous terminals presenting attachment zones such as zonula adherens, desmosomes and communicating junctions (gap junctions). "Focal contacts" between oolemma, and lateral microvillous extensions of follicle cells were also present. Unusual forms of contact between follicle cell microvilli and oocytes in the early stages of growing primordial and primary follicles were also observed. These consist of long, thin extensions penetrating into the oocyte through deep invaginations of the oolemma. The aid of high resolution SEM of specimens subjected to the ODO method clearly reveals their 3-D arrangement within the ooplasm. They appear as long tortuous microvilli coming very close to the nucleus, and in their course are closely associated with a variety of organelles such as Golgi vesicles, endoplasmic reticulum membranes and nascent forms of smooth endoplasmic reticulum. Using integrated observations by TEM and SEM, there may be as many as 3-5 "intraooplasmic processes" even in only one plane of fracture of an oocyte. Therefore, if the total volume of the oocyte and associated cells is considered, their amounts appear to be higher than previously reported. Thus, they have to be considered as normal devices of deep contact between the ooplasm and associated follicle cell extensions. The presence of such structures within the ooplasm in early developing follicles well coincides with the great increase in volume of the oocyte. Although it is commonly believed that the activation of the growing oocyte may depend on the numerous contacts between the oolemma and follicle cells (mostly via gap junctions), the finding of these additional intraoocytic extensions suggests that they may in someway contribute to the initiation of growth in the human. In fact, these microvilli penetrate deep into the ooplasm, much like a sword in its sheath.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7880592 TI - Fine structural aspects on auditory hair cell degeneration in the budgerigar, Melopsittacus undulatus, as induced by kanamycin. AB - The effects of kanamycin, an antibiotic of the aminoglycoside group, on the auditory sensory epithelium of the budgerigar, Melopsittacus undulatus, were examined using both scanning and transmission electron microscopes. Results show that the threshold of the auditory brainstem response increased in birds treated with kanamycin 200 mg/kg for 49 days. While the auditory sensory epithelium of the normal budgerigar consists of short and tall hair cells, and supporting cells, following kanamycin administration, the middle to proximal region of the epithelium of the inner ear showed degenerative changes, with the other parts remaining apparently intact. In the damaged region, the short hair cells were flattened, and the tall ones became heterogeneous in shape. Both types of cells contained many dense bodies in their cytoplasm; they were rounded in shape and homogeneously dense. Severely degenerated tall hair cells also contained many large vacuoles with heterogeneous contents. Because the dense bodies and large vacuoles were positive for acid phosphatase reaction, they were respectively judged to be primary lysosomes and secondary lysosomes containing degenerating cell debris. Most supporting cells in the impaired region were lower in cytoplasmic electron density, and their apical surface became enlarged in area. Some flattened short hair cells were situated on the apical part of the swollen supporting cells. This finding suggests that the short hair cells are pressed toward the scala media by the supporting cells. PMID- 7880593 TI - Locations of postganglionic nerve cells whose axons enter nerves originating from prevertebral ganglia. AB - Major nerve trunks that supply abdominal viscera contain axons of postganglionic neurons that originate in the coeliac ganglion, superior mesenteric ganglion, inferior mesenteric ganglia, hypogastric nerve ganglia and the sympathetic chain ganglia. Using the retrogradely transported neuronal marker Fast Blue, we mapped the distribution of labelled nerve cells after application of the dye to either the superior coeliac nerves, inferior coeliac nerves, superior mesenteric nerve, colonic nerves or hypogastric nerves. Distinctive patterns of nerve cell locations were associated with each nerve trunk. Within the coeliac ganglion, nerve cells that projected into the superior coeliac nerves were almost exclusively lateral, whilst neurons in the medial part of the coeliac ganglion and in the rostral pole of the superior mesenteric ganglion tended to project into the inferior coeliac nerves. Nerve cells located around the emerging superior mesenteric nerve in the superior mesenteric ganglion contributed the majority of axons to that nerve. Cells in both poles of the inferior mesenteric ganglia contributed the majority of postganglionic axons to the colonic nerves, but some cells in the caudal pole of the superior mesenteric ganglion also projected into the colonic nerves. Postganglionic axons in the hypogastric nerves originated from cells predominantly located in the caudal pole of the inferior mesenteric ganglion; however, cells in the rostral pole of the inferior mesenteric ganglia, the superior mesenteric, coeliac and hypogastric nerve ganglia also contributed some axons. Nerve cells of sympathetic chain ganglia projected into each of the nerve trunks; they were distributed rostro-caudally according to the nerve injected. PMID- 7880594 TI - Phagocytotic cells in the fish heart. AB - Comparatively little is known about host-defense activities in the fish heart. Investigations showed that intraperitoneally injected carbon particles are actively taken up by the cardiac endothelial cells of the medaka Oryzias latipes, but less so by those of the goldfish Carassius auratus and lemon tetra Hyphessobrycon pulchripinnis. (In vitro experiments confirmed these species differences in endocytic activities by these cells.) Electron microscopy revealed that endothelial cells of the medaka atrium have large cytoplasm with many organelles, and ingested carbon particles were observed within phagosomes of cardiac endothelial cells even at 4 degrees C. Phagocytic cells, which apparently reside in the heart, were found in all the species examined. These cells were located on the endothelial cells and developed cytoplasmic processes extending toward the heart lumen and/or the intercellular spaces of the endothelial cells. The heart with its resident phagocytes is proposed to function as a host defense organ--at least in certain fish species. PMID- 7880595 TI - Atomic force microscopy of embedment-free sections of cells and tissues. AB - The atomic force microscope (AFM) was applied for the first time to embedment free biological sections. Aldehyde-fixed tissues (kidney, liver etc.) of mice were postfixed with osmium tetroxide and cut into 500-700 nm thick sections after embedding of the tissue block in polyethylene glycol (PEG); the sections mounted on glass slides were deembedded and critical point-dried. The AFM images were collected in air from those tissue sections in a dynamic force mode. Solid-height mode images, which were comparable to transmission electron microscope (TEM) images, seemed to provide us more useful information than the solid-mode images which resembled scanning electron microscope (SEM) images. Internal structures including chromatin fibers in the nuclei and cytoplasmic organelles were clearly recognizable by AFM. Minute surface structures including the end-feet of renal podocytes were demonstrated. We confirm that a vertical resolution of 0.1 nm and a lateral resolution of 5-10 nm are attainable with the dynamic force mode of AFM using thin sections of tissues. The present paper proposes the usefulness of AFM for observation of biological materials without metal coating in a non-vacuous environment. PMID- 7880596 TI - BRCA1, BRCA2, BRCA3 ... a myriad of breast cancer genes. PMID- 7880597 TI - Local injection of OK-432/fibrinogen gel into head and neck carcinomas. AB - Immunotherapy with biological response modifiers (BRM) is a possible strategy against head and neck solid tumours. However, the rapid disappearance of BRM from the tumour area is one of the reasons for its limited clinical application. In this pilot study, fibrinogen gel containing OK-432 (a compound composed of attenuated Streptococcus pyogenes), an inducer of natural killer cells and T-cell cytotoxity, was injected directly into head and neck solid tumours of 15 patients. A dose of 5 Klinische Einheiten (KE) of OK-432 was reconstituted in 1 ml aprotinin and mixed with fibrinogen, the latter to maintain the OK-432 locally. 3 patients showed tumour regression, and in addition, we observed histological changes in the injected tumour of all patients. These results suggest that OK-432/fibrinogen gel generates a local immune response, leading to tumour regression. PMID- 7880598 TI - One-year follow-up of the 'Starting Again' group rehabilitation programme for cancer patients. AB - In a randomised prospective study, a brief structured rehabilitation programme, 'Starting Again', was evaluated over a follow-up year. 98 patients were assigned to the programme, and 101 to the control condition. The 11, 2-h sessions emphasised physical training, information and coping skills. Patients in the programme improved significantly more than the controls with respect to appraisal of having received sufficient information, physical training, physical strength and fighting spirit. Results indicate improvement with respect to the three areas focused on in the 'Starting Again' programme: physical training, information and coping skills training. PMID- 7880599 TI - A classification after radical cystectomy of patients with bladder cancer associated with schistosomiasis. AB - The aim of this study was to classify the bilharzial bladder cancer patients after radical cystectomy into several prognostic strata with increasing risk of recurrence. 310 patients through the period 1977-1983 at the National Cancer Institute of Cairo were systematically analysed for 12 variables evaluated after radical cystectomy. Eight factors were shown to have a significant influence on the recurrence-free survival curve after radical cystectomy namely: tumour stage, size, grade and location in the bladder, lymph node involvement, metastasis, renal insufficiency and urinary diversion. Using the proportional hazard model, five factors were significantly related to a lower recurrence-free survival, one major prognostic factor, tumour grade (G2 or G3) (relative risk estimate of 5.5), and four minor prognostic factors (relative risk estimates around 2), namely tumour diameter greater than 5 cm, anterior or trigonal location of the tumour, tumour stage (T3 or T4) and presence of renal insufficiency before surgery. Four prognostic strata have been defined in relation to the presence of these prognostic factors. This classification was validated on a second sample of 122 patients by comparing for each prognostic stratum, the recurrence-free survival curve observed on this sample and the corresponding predicted curve by Cox model. No statistically significant difference could be detected. This classification of bladder cancer patients appears to be adequate for bilharzial bladder cancer patients after radical cystectomy, at least in the conditions they presented and were treated for at the NIC in Cairo. PMID- 7880600 TI - High dose level radiation therapy for local tumour control in esthesioneuroblastoma. AB - Esthesioneuroblastoma is an uncommon tumour of neural crest origin arising in the nasal cavity. This paper is a retrospective review of 7 patients with esthesioneuroblastoma treated at a single institution from May 1974 to July 1990. 5 patients were treated with radiation therapy alone and 2 patients were irradiated after surgical resection. No local or regional occurrence was observed in any patient at 6 months, or at 1, 3, 6, 11.5 and 12 years following treatment. One patient died of intercurrent disease 6 years after radiation therapy. 2 patients died of disease, 1 of distant metastasis at 6 months and the other patient of meningeal carcinomatosis and distant metastases 1 year after treatment. One patient is alive with distant metastases 1 year after treatment. None of the patients experienced significant complications of irradiation. High dose irradiation (60 Gy or more) alone or in combination with resection is an effective local treatment modality for esthesioneuroblastoma. PMID- 7880601 TI - Testicular lymphoma: a population-based study of incidence, clinicopathological correlations and prognosis. The Danish Lymphoma Study Group, LYFO. AB - In a Danish population-based non-Hodgkin's lymphoma registry, 2687 newly diagnosed patients were registered from 1983 to 1992. 39 had testicular involvement (TL) (incidence 0.26/10(5)/year). Median age was 71 years. 24 cases had localised and 15 had disseminated disease. Histologically, all cases were diffuse (65% diffuse centroblastic type). Of the 27 tested, 11% were of T- and 89% of B-immunophenotype. In localised cases, where surgery was supplemented by combination chemotherapy (CCT), the relapse rate was 15.4%. The relapse rate for cases with localised disease treated with other regimens (orchiectomy and/or radiotherapy) was 63.6% (P < 0.05). Median relapse-free survival was 28 and 14 months, respectively. Overall 5-year survival for all cases was 17%. Adverse prognostic factors at the univariate level were stage IV, constitutional symptoms, serum lactic dehydrogenase elevation and performance score (WHO 3-4). It is suggested that the treatment of stage IE/IIE TL should include early CCT and CNS prophylaxis. PMID- 7880602 TI - Response to second-line weekly cisplatin chemotherapy in ovarian cancer previously treated with a cisplatin- or carboplatin-based regimen. AB - Response to a second-line weekly cisplatin chemotherapy in ovarian cancer previously treated with cisplatin- or carboplatin-based regimens was analysed in a clinical series observed between 1984 and 1991. Women who achieved pathological complete response or pathological optimal partial remission after first-line cisplatin- or carboplatin-based regimens were treated at recurrence or progression, occurring at least 4 months after first-line treatment, with second line chemotherapy. A total of 72 women were included in the analysis. Second-line chemotherapy regimens were: cisplatin 1 mg/kg weekly for seven courses plus epirubicin 70 mg/m2 intravenously (i.v.) every 3 weeks for three courses (28 subjects), cisplatin 1 mg/kg plus etoposide 90 mg/m2 i.v. weekly for a total of seven courses (11 subjects) and cisplatin 1 mg/kg weekly for nine courses plus carboplatin 250 mg/m2 every 3 weeks for three courses (33 subjects). Of the 72 women, 22 (31%, 14 clinical, 8 pathological) had a complete response and 28 (39%), a partial response (24 clinical, 4 pathological). The 24-month cumulative survival probability was 63% in women with complete response, 32% in those who had partial response, but all the 22 non-responders died within 24 months from diagnosis of recurrence (log rank test P < 0.05). The frequency of complete response and partial response increased with the interval between first diagnosis and recurrence: among the 33 women who had recurrent disease to < 18 months from first diagnosis, complete response or partial response was obtained in 20 (61%) subjects, this figure was 67% (14 out of 21 women) among subjects who had recurrent disease between 18 and < 36 months from first diagnosis and 89% (16/18) among those who had recurrence > or = 36 months. In comparison with women who had recurrence 4- < 18 months from first diagnosis, the OR of response was 1.3 (95% CI 0.4-4.1) for those who had recurrence between 18 and < 36 and 5.2 (95% CI 1.1 24.3) for those who had recurrence > or = 36 months from surgery (chi 1(2) trend p < 0.05). Survival rate after the end of second line chemotherapy for women who relapsed 4- < 18 months, 18- < 36 or 36 months or more after surgery were, respectively, 24, 20 and 67% (log rank test, P < 0.05). Age at first diagnosis, histology, stage, and grading of the disease at first diagnosis and site of recurrence were not associated with response to second-line therapy. PMID- 7880603 TI - Clinical evaluation of serum tissue polypeptide-specific antigen (TPS) in non small cell lung cancer. AB - M3 is an epitope of the tissue polypeptide antigen detectable in the serum by immunoradiometric assay. This epitope is referred to as tissue polypeptide specific antigen (TPS). We examined the pretreatment TPS level of 160 non-small cell lung cancer (NSCLC) patients and 71 patients who suffered from non-malignant pulmonary diseases. The upper limit of normal values was 140 U/l. Using this cutoff, the sensitivity and specificity were 36 and 90%, respectively. The TPS was significantly higher in NSCLC patients with an advanced stage, a mediastinal lymph node involvement or a poor performance status. This level was significantly higher in the group of patients for whom the disease proved to progress during chemotherapy. In univariate analysis, patients with a high TPS level proved to have a shorter survival than patients with a TPS < or = 140 U/l. In Cox's model analysis, performance status, stage of the disease and serum TPS were the only significant prognostic variables. The low sensitivity of TPS precludes its use for diagnosis. However, the pretreatment TPS level adds information to the management of NSCLC inasmuch as it predicts a low sensitivity to chemotherapy and a poor prognosis. PMID- 7880604 TI - Weekly doxorubicin with or without high-dose medroxyprogesterone acetate in hormone-resistant advanced breast cancer. A randomised study. The Norwegian Breast Cancer Group. AB - In a randomised study, 218 patients with advanced breast cancer, resistant to hormone therapy, received either doxorubicin 20 mg every week (Awkly) alone or Awkly combined with high doses (1000 mg daily) of oral medroxyprogesterone acetate (HD-MPA). Of the 210 evaluable patients, the response rates were 26% [95% confidence interval (CI) 18-34%] for Awkly and 38% (95% CI 29-47%) for Awkly + HD MPA (P = 0.08). There was no significant difference with regard to duration of response. Median survival was 11 months in both groups. Considerable toxicity was seen from HD-MPA, particularly weight gain and fluid retention. The present study provides evidence that, in concordance with preclinical studies and a previous randomised study, interaction between chemotherapy and HD-MPA may exist in breast cancer normally resistant to hormone therapy. For further studies, other gestagens and/or a dose reduction could be investigated. PMID- 7880605 TI - Adult Wilms' tumour: review of 22 cases. AB - The Institut Gustave Roussy experience with nephroblastoma in 22 patients older than 16 years during a 19-year period (1973-1992) was retrospectively reviewed. All patients underwent a nephrectomy. There were 4 stage I, 8 stage II, 3 stage III and 7 stage IV patients. Initial postnephrectomy therapy included single modality approach in 7 patients (radiotherapy in 1 and chemotherapy in 6) and combined modality approach (radiotherapy and chemotherapy) in 15 patients. The agents used most often were actinomycin, vincristine and doxorubicin. 2 of 7 (29%) and 7/15 (47%) patients are disease-free survivors after first-line treatment. Salvage chemotherapy was given in 13 patients. Only 1 patient experienced a subsequent sustained complete remission. After a mean follow-up of 100 months (range 10-240), 12/22 patients (55%) are alive, including 10 who are disease-free (45%). We confirm that adult patients are likely to have more advanced disease and poorer prognosis than children. The combined modality approach is more active than one-modality therapy. Aggressive treatment, including the three-drug regimen actinomycin+vincristine+doxorubicin, regardless of stage, associated to irradiation starting from stage II, is recommended. PMID- 7880606 TI - Prognostic significance of tissue polypeptide-specific antigen (TPS) in patients with advanced non-small cell lung cancer. AB - In this study, we evaluated the prognostic value of the tumour marker, tissue polypeptide-specific antigen (TPS), in 203 patients with non-small cell lung cancer (NSCLC), and related this to several other known prognostic factors. TPS was significantly correlated with lactate dehydrogenase (LDH), gamma glutamyltranspeptidase and alkaline phosphatase, and the median level of TPS in patients with stage 4 disease was significantly higher as compared to stage 3A and 3B disease. In the univariate analysis, performance status, stage of disease, LDH, alkaline phosphatase, a histology of undifferentiated large cell carcinoma and TPS all had a statistically significant association with survival. Multivariate analysis showed that stage of disease, performance status, histology and TPS were the most important prognostic factors. TPS has prognostic significance for survival in patients with advanced NSCLC, independent from performance status and stage of disease. PMID- 7880607 TI - In vivo cell kinetic measurements in human oesophageal cancer: what can be learned from multiple biopsies? AB - The importance of intratumour variability of cell kinetics was studied in 60 patients with cancer of the oesophagus. Five biopsies per tumour were taken. The labelling index, S-phase duration and potential doubling time (Tpot) were measured using flow cytometry. The mean Tpot value was 5.56 +/- 4.43 days (+/- 1S.D.) for adenocarcinomas and 4.40 +/- 2.45 days (+/- 1S.D.) for squamous cell carcinomas. These values were statistically significantly different. Although intratumour variation in Tpot measurements occurred, the intertumour variability was more important (P < 0.00001). This feature permits classification of tumours into slow and fast proliferating groups, leaving an intermediate group of tumours that could not be unequivocally categorised. The relative distribution of tumours into these three categories depends on the intratumour and intertumour variability of Tpot, and on the cut-off values used. Increasing the number of biopsies from one to five reduces the number of non-classifiable tumours. PMID- 7880608 TI - Medullary carcinoma of the breast, prognostic importance of characteristic histopathological features evaluated in a multivariate Cox analysis. AB - In this study of 136 breast cancers with medullary features (MC), registered in the Danish Breast Cancer Cooperative Group (DBCG) from 1982 to 1987, we confirmed the prognostic importance of a new definition of medullary carcinoma of the breast (MC newdef) which was recently proposed by us, deduced from a previous study of a corresponding tumour material (DBCG 77-82). However, the individual histological criteria did not have the same prognostic importance as in our previous study, although prognostic trends were the same. To further improve and validate the diagnostic criteria, we combined the two populations and performed a multivariate Cox regression analysis. In the final Cox model, four histological parameters retained positive prognostic importance: (1) predominantly syncytial growth pattern, (2) no tubular component, (3) diffuse stromal infiltration with mononuclear cells and (4) sparse necrosis. We propose that these criteria are emphasized in the histological diagnosis of medullary carcinoma of the breast. PMID- 7880609 TI - Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. AB - A series of 325 prostatic adenocarcinomas with a long-term clinical follow-up were subjected to light microscopic analysis of histological prognostic factors, including three grading systems (Gleason score, WHO grade, nuclear grade), perineural infiltration of the tumour (PNI), tumour infiltrating lymphocytes (TIL) and the presence of apoptotic cells (APO). All three histological classifications correlated significantly with the prognosis, but in multivariate analysis, the Gleason score was superior to the WHO grading or nuclear grading in predicting patient survival. PNI was significantly related to poor differentiation of the tumour, its progression and ominous disease outcome, particularly in T1-2MO tumours. The density of TIL was independent of the tumour differentiation, and absent or weak TIL were signs of a high risk of tumour progression and of a fatal disease. Apoptotic cells were commonly detected in poorly differentiated tumours and apoptosis was related to disease progression and low survival probability. The results suggest that the Gleason score, PNI and the density of TIL should be included in routine pathology reports, to be used by clinicians while making therapeutic decisions in prostatic cancer. PMID- 7880610 TI - The development of anti-interleukin-2 (IL-2) antibodies in cancer patients treated with recombinant IL-2. AB - Serum samples from 217 cancer patients participating in phase I/II clinical trials were analysed for the development of anti-interleukin-2 (IL-2) antibodies. Patients received recombinant human IL-2 (rIL-2) by continuous intravenous infusion (c.i.v.; n = 86) or by subcutaneous (s.c.) injections (n = 131). Both patient groups developed anti-rIL-2 antibodies as detected by ELISA with similar frequencies and titres: 52% (median titre, 23) and 47% (median titre, 24), respectively. Using an IL-2-dependent T-cell proliferation assay, sera from 5 c.i.v.-treated patients (6%) and 13 s.c.-treated patients (10%) exhibited neutralising activity. Immunoabsorption studies with rIL-2-coated beads, demonstrated that in 8 of 15 patients with neutralising sera, the neutralising activity was correlated with specific anti-rIL-2 immunoglobulin. All 8 patients had received at least two cycles of rIL-2 by s.c. injections. Specific IL-2 neutralising activity affected both recombinant and natural IL-2 in all 8 patients. Development of anti-rIL-2 antibodies, irrespective of whether these exhibited neutralising activity or not, did not affect the frequency or duration of clinical responses. PMID- 7880611 TI - Survival in patients with recurrent glioma as a measure of treatment efficacy: prognostic factors following nitrosourea chemotherapy. AB - The assessment of efficacy of treatment in patients with recurrent glioma is notoriously difficult, and survival is the most objective endpoint. Between 1970 and 1992, a cohort of 211 patients with recurrent glioma received nitrosourea based chemotherapy at the time of disease progression. The median survival from the start of chemotherapy was 7 months, with 30% 1-year and 10% 2-year survival probabilities. One-year survival was 22% in 147 patients with recurrent high grade astrocytoma, 41% in 37 patients with low-grade astrocytoma and 45% in 24 patients with oligodendroglioma. Age, histological grade and Karnofsky performance status (KPS) at recurrence were independent prognostic factors for survival on multivariate analysis. Based on patients' age, tumour grade and KPS, it was possible to define three distinct prognostic groups with 1-year survival probabilities of 60, 21 and 17% (P < 0.005). Response to chemotherapy was difficult to assess but correlated with prognostic subgroup, with highest response rate (46%) in the most favourable group and lowest (13%) in the poor prognostic group. In patients with recurrent glioma, patient and tumour parameters are the major determinants of outcome which are identical to prognostic factors at the time of primary diagnosis. They can be used to provide prognostic information for the individual patient, and to stratify patients particularly in trials assessing the efficacy of novel treatments. PMID- 7880612 TI - DNA content as a predictor of clinical outcome in soft tissue sarcoma patients. AB - The prognostic relevance of cellular DNA content has been shown for a variety of human malignancies. However, only a few studies concerning soft tissue sarcomas have been published. Biopsies of 81 patients with soft tissue sarcomas, referred for primary or secondary surgery, were analysed by flow cytometry to determine cellular DNA content of tumours. Most patients (60/81) already had one or more local recurrences at the time of first presentation at Essen University. The median age of the patients was 45 years (range 14-79). 44 (54%) patients had euploid and 37 (46%) had aneuploid tumours. Age, sex, and tumour localisation (trunk versus extremity) were equally distributed between euploid and aneuploid sarcoma patients. The median follow-up was 69 months (range 9-312). The median survival time for euploid and aneuploid tumours was 84 and 30 months, respectively (P < 0.0005). In the univariate analysis, ploidy, S-phase percentage, localisation and tumour grading were significant predictors of survival, whereas in the multivariate analysis, only DNA content and tumour localisation were independent prognostic variables for survival. PMID- 7880613 TI - Identification of potassium flux pathways and their role in the cytotoxicity of estramustine in human malignant glioma, prostatic carcinoma and pulmonary carcinoma cell lines. AB - Clinically-used drugs such as furosemide, bumetanide and cardiac glycosides, are modulators of transmembrane fluxes of cations. Recently, it has been suggested that the regulation of intracellular cation concentrations could be a primary target for anti-neoplastic drugs, and that the cytotoxic activity may be altered by inhibitors of cation fluxes at the level of the plasma membrane. Therefore, we investigated the mechanisms by which cations are translocated across the plasma membrane of malignant glioma (U251 MG), prostatic carcinoma (PC3) and pulmonary carcinoma (P31) cell lines. The interactions between cation flux inhibitors and the cytotoxicity of estramustine were also evaluated. Ouabain, the classical inhibitor of Na+, K+ATPase, markedly reduced 86Rb (K+) influx in all three lines, indicating that this ion transport system is present in the cells. Furosemide and especially bumetanide inhibited the 86Rb influx, indicating the presence of the Na+, K+, Cl- co-transport system. The potassium channel blocker, tetraethylammonium, but not apamin reduced the influx of 86Rb showing that high conductance K+ channels are present, but that channels of low conductance probably do not exist in these cell lines. The Na+, K+, Cl- co-transport inhibitors furosemide and bumetanide significantly reduced cytotoxicity of estramustine in P31 cells, whereas no interaction between other K+ flux inhibitors and the anti-neoplastic drugs were detected in any of the cell lines investigated. Thus, the data show that Na+, K+, ATPase and NA+, K+, Cl- co transport systems and K+ channels of high conductance are present in malignant glioma (U251 MG), prostatic carcinoma (PC3) and pulmonary carcinoma (P31) cell lines, and that inhibition of the Na+, K+, Cl- co-transport system in P31 is associated with reduced cytotoxicity of estramustine. The results justify further studies evaluating the role of these cation flux pathways in terms of targets for anti-neoplastic therapy. PMID- 7880614 TI - Stable analogues of the antitumour agent trimelamol retain in vitro cytotoxicity in drug-sensitive and resistant rodent and human cell lines. AB - In spite of clinical activity in heavily-pretreated ovarian cancer, the antitumour s-triazine trimelamol [TM; tris(hydroxymethyl)-tris(methyl)melamine] had to be withdrawn from further clinical studies due to formulation difficulties related to instability. A synthetic programme has produced tris(hydroxymethyl) analogues containing electron-withdrawing groups in place of methyl triscyanomethyl CB 7669, tristrifluoroethyl CB 7639, CB 7529 and trispropargyl CB 7547, all showing markedly superior stability to TM. Chemosensitivity testing of analogues (MTT assay, continuous exposure) using a panel of rodent and human cell lines showed activity close to that of TM, e.g. for the CH1 human ovarian cancer cell line. IC50 values were TM 23.4 microM, CB 7639 30.5 microM, CB 7529 29.5 microM, CB 7547 28.5 microM and CB 7669 27.3 microM. CB 7669 and CB 7639 required prolonged exposure (> 12 h) in order to exhibit equivalent cytotoxicity to a 2-h exposure to TM. Thus, rather than administration as a single daily dose, the stable analogues may be more suited to prolonged infusion, which was suggested as being a more beneficial regimen in clinical trials with TM. In line with clinical observations indicating the efficacy of TM in platinum-refractory ovarian cancer, we saw no significant cross-resistance to TM or CB 7529 in a range of platinum sensitive and acquired-resistant cell line pairs or in an alkylating-agent resistant cell line, despite TM's ability to crosslink DNA. Data obtained using cell lines with acquired resistance to TM, CB 7669 and formaldehyde (released in the breakdown of TM) suggest a pivotal role for formaldehyde and a more minor role for alkylating activity in the mechanism of action of the N (hydroxymethyl)melamines in vitro. Further clinical trials of these compounds are eagerly awaited, and their usefulness as second-line chemotherapy for heavily pretreated ovarian cancer deserves further investigation. PMID- 7880615 TI - Viscum album L. extracts reduce sister chromatid exchanges in cultured peripheral blood mononuclear cells. AB - Increasing concentrations of Viscum album L. extracts were shown to significantly reduce sister chromatid exchange (SCE) frequency of phytohaemagglutinin (PHA) stimulated peripheral blood mononuclear cells (PBMC) of healthy individuals. This decrease of SCE could not be explained either by changes in lymphocyte subpopulations, by cytostatic effects of the drug or by accelerated proliferation of PHA-stimulated PBMC. Currently, no other cells tested have shown this effect. One therapeutic effect of these anti-mutagenic drugs could be a stabilisation of mononuclear blood cell DNA. PMID- 7880616 TI - Targeting of tumours with murine and reshaped human monoclonal antibodies against placental alkaline phosphatase: immunolocalisation, pharmacokinetics and immune response. AB - Anti-tumour monoclonal murine and humanised (reshaped human) antibodies (H17E2 and Hu2PLAP, respectively) against placental alkaline phosphatase (PLAP), radioactively labelled with indium-111 (111In) and iodine-123 (123I), were evaluated for their ability to localise mainly testicular and ovarian tumours in sequential pilot studies of the Hammersmith Oncology Group. 33 patients with active primary and/or metastatic testicular cancer were studied with the [111In]- or [123I]H17E2 antibody. 8 patients with testicular cancer were studied with the same antibody after being rendered free of disease after induction chemotherapy and surgical resection of residual tumour. 3 additional patients, 2 with ovarian cancer and 1 with testicular seminoma, were studied with [111In]H17E2 via a macrocyclic chelating agent (DOTA). 7 patients; 5 with ovarian cancer, 1 with breast cancer, and 1 with gastric cancer, received the reshaped human Hu2PLAP antibody [111In]DOTA labelled. One of these was imaged twice, with H17E2- and Hu2PLAP-DOTA-111In, respectively. In the initial 33 patients with active primary and/or metastatic testicular cancer, the presence of tumour was confirmed and correlated well with conventional radiological diagnostic methods, and in addition, the antibody scan revealed the presence of active disease in 2 patients with negative conventional imaging, but elevated serum tumour markers. In the 8 patients with complete remission (CR), imaging studies with the radiolabelled antibody did not show any localisation. The best images were obtained at 24 and 48 h after the [123I]- and [111In]H17E2, respectively. None of these patients developed human anti-mouse antibody responses (HAMA). Successful imaging with the reshaped human antibody, Hu2PLAP-DOTA-111In, was seen in 3 patients with PLAP positive tumours (2 ovarian and 1 gastric cancer). The 3 negative patients were 1 in complete remission, 1 with PLAP-negative tumour and 1 who cleared the Hu2PLAP antibody immediately after infusion due to the presence of anti-chelating agent (anti-DOTA) antibodies from a previous H17E2-DOTA-111In scan. One patient with PLAP-negative breast carcinoma had a false-positive scan with Hu2PLAP, showing localisation to the pleural effusion. Antibody pharmacokinetics showed a mean t1/2 beta = 73.1 +/- 30.2 h (n = 5) for Hu2PLAP versus t1/2 beta = 27.2 +/- 5.9 h (n = 3) for H17E2 (P < 0.05). 2 patients receiving Hu2PLAP were excluded due to the rapid clearance of the radiolabel as a result of the presence of high HAMA and anti-chelate antibody levels, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7880617 TI - Urinary excretion of growth factors in patients with ovarian cancer. AB - The levels of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) were analysed in 24-h urine samples from patients with ovarian malignancies, benign ovarian tumours, and healthy controls by specific radioimmunoassays. No significant difference in total urinary immunoreactive EGF excretion between the groups was detected. However, 79% (23/29) of the patients with ovarian carcinomas excreted TGF-alpha (median 12.6 pmol/24 h), whereas only 17% (2/12) of the patients with benign ovarian tumours and 23% (3/13) of the controls did so. The difference between cancer patients and controls was highly significant (P < 0.001). Analyses of the urine samples separated by gel filtration revealed a greater molecular heterogeneity of EGF and TGF-alpha in cancer patients than in controls. High and low molecular weight forms of EGF were able to bind to the EGF receptor and to induce anchorage-independent growth. After surgical reduction of the tumour, a distinct decrease of urinary high molecular weight forms was observed. Thus, some macromolecular growth factors seem to be associated with epithelial ovarian carcinomas. PMID- 7880618 TI - Interferon alpha and 5'-deoxy-5-fluorouridine in colon cancer: effects as single agents and in combination on growth of xenograft tumours. AB - Interferon-alpha (IFN-alpha) enhances the activity of the 5-fluorouracil (5-FU) prodrug 5'-deoxy-5-fluorouridine (5'-dFUrd) in colorectal cancer cells in vitro by upregulating the enzyme pyrimidine nucleoside phosphorylase (PNPase), which is responsible for converting 5'-dFUrd to 5-FU. We examined whether such enhancement also occurs in vivo using human colorectal xenografts in nude mice. The Co-115 line has high basal levels of PNPase and the enzyme level was increased in tumours from mice treated for 3 weeks with 50,000 IU/day (5 days/week) of IFN alpha A/D. The prodrug 5'-dFUrd (200 mg/day, 5 days/week) had a much greater antitumour activity than 5-FU had when it was used at an approximately equitoxic dose (20 mg/day, 5 days/week). However, because of the high activity of 5'/dFUrd as a single agent, no enhancement by IFN-alpha A/D was observed. Studies on xenografts of WiDr cells indicated that this line is much less sensitive to 5' dFUrd. However, treatment of animals with IFN-alpha A/D at doses of 75,000 IU/day or 150,000 IU/day resulted in significant inhibition of WiDr tumour growth. Combination treatment with 75 mg/kg/day or 150 mg/kg/day of 5'-dFUrd resulted in enhanced antitumour activity, particularly at the higher dose of IFN-alpha A/D. Synergy of this drug combination was confirmed by isobologram analysis. Analysis of PNPase levels in WiDr tumours, excised from mice treated with IFN-alpha A/D, demonstrated that the enzyme activity was increased by IFN-alpha in a dose dependent manner. Slight increases were also seen in normal liver and intestine from the same animals. Our results indicate that modulation of converting enzymes for anticancer prodrugs by cytokines could be a novel therapeutic strategy for combination therapy of colorectal cancer. PMID- 7880619 TI - Soluble intercellular adhesion molecule-1 (ICAM-1) is released into the serum and ascites of human ovarian carcinoma patients and in nude mice bearing tumour xenografts. AB - We have demonstrated that patients with ovarian carcinoma have higher levels of soluble intercellular adhesion molecule-1 (ICAM-1) in their serum and ascitic fluids than serum from normal individuals and non-neoplastic gynaecological disease or ascites from patients with cirrhosis. In order to investigate the source of the ICAM-1, and to study the mechanisms which regulate ICAM-1 release in ovarian carcinoma, we have employed the nude mouse model system. Three different human ovarian carcinoma (HOC) cell lines were grown as ascitic tumours in the peritoneal cavity of nude mice. HOC xenografts harvested from nude mice expressed comparable levels of ICAM-1 on their cell surface. Human ICAM-1 was detected, with a species-specific ELISA, in serum and ascitic fluid of tumour bearing mice, confirming that the tumours were the source of the ICAM-1. The three HOC xenografts showed different levels of ICAM-1 release, but within each xenograft model the level of ICAM-1 in serum and ascitic fluid correlated with the tumour burden. The level of ICAM-1 released by the HOC xenografts could be increased by in vivo treatment with interferon gamma (IFN-gamma). Interleukin 1 (IL-1), tumour necrosis factor (TNF) and IFN gamma increased the cell surface expression of ICAM-1 and caused the release of soluble ICAM-1 from HOC cells established in vitro. The nude mouse provides a useful system in which to study the effects of modulating ICAM-1 release on the progression of ovarian carcinoma and suggests that measuring ICAM-1 levels in the blood or ascites of patients may provide an indication of tumour burden. PMID- 7880620 TI - Autolymphocyte therapy--I. In vivo tumour-specific adoptive cellular therapy of murine melanoma and carcinoma using ex vivo activated memory T-lymphocytes. AB - Autolymphocyte therapy (ALT) is tumour-specific adoptive cellular therapy of neoplastic disease based upon non-specific ex vivo activation of autologous peripheral blood lymphocytes (PBL), using the supernatant derived from a previously prepared one-way mixed lymphocyte culture (MLC). To determine the requirement for tumour antigen during the activation process, splenocytes from C57BL/6J healthy syngeneic mice (HSM) and tumour-bearing mice (TBM) were activated ex vivo using a MLC-supernatant (MLCS). Ex vivo activation was performed both in the presence (HSM splenocytes) and absence (TBM splenocytes) of a 3M KC1 syngeneic tumour-antigen (STA) extract prepared from Lewis lung (3LL) carcinoma, B16 melanoma, or normal lung. Immunophenotyping of splenocytes pre- and post-activation by MLCS plus STA or MLCS only revealed expansion of activated CD44+ (memory) T-cells. Ex vivo tumour-specific cytotoxicity was demonstrated using MLCS-activated (TBM) or MLCS + STA-activated (HSM) splenocytes against 3LL or B16 target cells. CD44+ T-cells (ALT-cells) were then infused into synegeneic 3LL and B16 TBM. Significant antitumour activity was detected in 3LL and B16 TBM receiving cells from normal mice that were activated with MLCS in the presence of 3LL or B16 STA, respectively, and in 3LL and B16 TBM receiving splenocytes from 3LL-TBM and B16-TBM, respectively, activated by MLCS alone. Infusions of 3LL derived or B16-derived ALT-cells into HSM provided specific immunity on tumour challenge. No antitumour activity was seen in 3LL and B16 TBM receiving fresh TBM splenocytes, ALT-cells derived from HSM which were activated ex vivo using MLCS without antigen, normal lung tissue as antigen, or using MLCS-activated splenocytes without STA derived from reciprocal TBM. Ex vivo depletion of CD44+ cells or Thy-1.2+ T-cells abrogated all antitumour activity in TBM and in HSM challenged with tumour. Depletion of NK-1.1+ natural killer (NK)-cells had no effect on antitumour efficacy. These data suggest that tumour-specific adoptive cellular therapy is possible using ex vivo activated HSM splenocytes with STA, or TBM splenocytes activated ex vivo without STA, and that these antitumour effects are dependent on CD44+ memory T-cells. PMID- 7880621 TI - Prognostic significance of pS2 mRNA in breast cancer. AB - The oestrogen-inducible pS2 protein has previously been associated with good prognosis for breast cancer patients. In 1987-1988 a series of 145 primary breast cancers were examined for pS2 mRNA using northern blots. On recent examination of mortality data, we were unable to find any association between tumour pS2 positivity and patient survival. One patient in 6 died within 5 years of surgery, regardless of pS2 status. In the oestrogen receptor positive/progesterone receptor positive tumour subgroup of patients, we found no evidence of increased survival for pS2-positive tumours. These results do not support use of pS2 as an indicator of increased survival in an average breast cancer patient population. PMID- 7880623 TI - Peri-operative hormones and prognosis in breast cancer. PMID- 7880622 TI - Cancer and the heat shock response. PMID- 7880624 TI - Tropisetron (Navoban) compared with alizapride in the control of emesis induced by cyclophosphamide-containing regimens. PMID- 7880625 TI - The treatment of progressive ovarian carcinoma with D-Trp-LHRH (Decapeptyl). Gruppo Oncologico Nord ovest (GONO) PMID- 7880626 TI - Acute morphine intoxication during high-dose recombinant interleukin-2 treatment for metastatic renal cell cancer. PMID- 7880627 TI - Prognostic impact of DNA content and a classification system for ploidy (AUER classification) in primary fallopian tube carcinoma (FTC) PMID- 7880628 TI - Phase II study of 4'epirubicin in advanced squamous cell oesophageal cancer. PMID- 7880629 TI - Pilot study of high dose fenretinide and vitamin A supplementation in bladder cancer. PMID- 7880630 TI - The ultimate referral. Why the hardest thing to do might be the kindest thing to do. PMID- 7880631 TI - Hospice care versus home health care: regulatory distinctions and program intent. AB - A significant percentage of community health care agencies have both a certified hospice and home health program component. These agencies commonly utilize many of the same "cross-trained" staff in both programs. However, these programs are not identical in focus, scope and regulatory practice. This paper examines both certified hospice and certified home health care practice from the standpoint of the Code of Federal Regulations (CFR). The distinctions made in these two sets of regulations (hospice, 42 CFR 418.50-.100 and home health, 42 CFR 484.10-.52) point to important differences in program and management practice. PMID- 7880632 TI - COPD and hospice: collaboration or conflict. PMID- 7880633 TI - Productivity of hospice nurses. PMID- 7880634 TI - Becoming a hospice volunteer. PMID- 7880635 TI - Volunteer services. AB - Hospice volunteers can be the link between professional staff and members of a family suffering the impending loss of a loved one. By helping with practical needs and providing emotional support, volunteers may serve a crucial role in the healing of the grieving family. PMID- 7880636 TI - What one small hospice learned from its grieving children's program. AB - Bath-Brunswick Hospice, a small hospice in Brunswick, Maine, began their Grieving Children's Program in 1991. This article discusses the unique learning experience this program has been for this hospice. An overview of the entire organization and the Grieving Children's Program is given, as well as observations about how the program has impacted this hospice. Many aspects of this Grieving Children's Program that are different from the usual hospice work are discussed, and the topics addressed include: Serving Children! The Training, Coordination and Support of Volunteers; The Need for Professional Consultants; Hospice's Mission. PMID- 7880637 TI - Effective hospice volunteers: demographic and personality characteristics. AB - The purpose of the study was to examine demographic and personality characteristics of highly effective hospice volunteers. Volunteer coordinators of all Texas Hospice Organization member hospices were asked to select their most committed and effective volunteers to participate in the study. Volunteers had above-average incomes, were predominately white, female, active in other voluntary activities, and motivated by their own experiences with death of a loved one. The largest proportion of female volunteers (27.3 percent) were extroverted, sensing, feeling, judging personality types (ESFJ), whereas, for male volunteers, the largest proportion (20.8 percent) were introverted, sensing, thinking, judging personality types (ISTJ). This information will be beneficial in recruitment, training, and retention of hospice volunteers. PMID- 7880638 TI - Denial and terminal illness. AB - Denial in the terminally-ill is often seen as a problem that health care professionals, particularly social workers need to fix. Rather than seeing denial as a part of acceptance, it is seen as just the opposite. Denial surfaces to establish control in an uncontrollable situation such as terminal illness. The social worker's challenge is to help the patient and family see their own strengths and make their own decisions. As the patient and family regain some control over their lives, denial is often replaced with other, more functional coping mechanisms. PMID- 7880639 TI - Social workers and volunteers at different stages of palliative care. PMID- 7880640 TI - You never know.... PMID- 7880641 TI - On doing some wrong. PMID- 7880643 TI - Increasing minority access to hospice care. PMID- 7880642 TI - Relationship between right-to-die and satisfaction with life. AB - To examine the relationship between right-to-die attitudes and satisfaction with life, 108 institutionalized elderly residents in a random sample were interviewed in the summer of 1990. Overall, 55 percent responded Yes or Probably Yes to a question pertaining to the legalization of some form of control of death circumstances. Those who were moderately or most satisfied with their lives more often responded Yes or Probably Yes to the legalization question. The purpose of this article is to discuss findings from a random sample of 108 institutionalized elderly concerning the relationship between their responses to right-to-die questions and their self-reported satisfaction with life. PMID- 7880644 TI - Death and spirituality: a nurse's perspective. PMID- 7880645 TI - Preliminary assessment: the Pain Inventory and the Pain Coping Tool. AB - The purpose of this research study was to report the development and preliminary psychometric testing of the Pain Inventory and the Pain Coping Tool. The Pain Inventory was developed to measure cognitive factors believed to impact upon the pain experience. The Pain Coping Tool was developed to measure coping strategies and behaviors believed to be effective in dealing with the pain experience. Forty nursing doctoral students, head nurses, and clinical nurse experts rated the items to establish content validity. Initial testing for reliability found coefficient alphas to be adequate for new scales. Construct validity was established by significant correlations found between these tools and the Pain Intensity and Pain Distress Scales. These findings must be viewed as preliminary based on the small sample of 80 metastatic cancer patients interviewed for this study. PMID- 7880646 TI - Spiritual care in terminal illness: practical applications for nurses. PMID- 7880647 TI - "Little guy.". PMID- 7880648 TI - A visit with Mother Teresa and the Missionaries of Charity in Calcutta. PMID- 7880649 TI - Imaging the asymmetrical DNA bend induced by repressor activator protein 1 with scanning tunneling microscopy. AB - The yeast Repressor Activator Protein 1 (RAP1) binds a 13-bp consensus found in many transcriptional regulatory regions, in silencer elements, and in telomeric repeat DNA of Saccharomyces cerevisiae. Gel retardation assays suggest that RAP1 bends DNA as it binds, with the vertex of the angle located 5' of the consensus. We show that removal of 230 aa in the N-terminus of RAP1 reduces the aberrant electrophoretic mobility of the protein-DNA complex, while removal of a C terminal domain of RAP1 causes even greater distortion. To demonstrate that the aberrant electrophoretic mobility is really due to a bend in the double helix, the RAP1-DNA complex was analyzed by Scanning Tunnelling Microscopy (STM). The efficiency and accuracy of binding is checked in parallel by standard Transmission Electron Microscopy (TEM). Due to the use of high-angle shadowing of freeze-dried samples at low temperatures, the STM images allow us to confirm that RAP1 binding induces a DNA bend > 50 degrees, while the binding of the minimal DNA-binding domain shows significantly less distortion of the DNA helix. PMID- 7880650 TI - Applications of a slow-scan CCD camera in protein electron crystallography. AB - A Gatan 1024 x 1024 slow-scan charge-coupled device (CCD) camera has been interfaced to a JEOL4000EX electron cryomicroscope and explored for its usefulness in the electron crystallographic analysis of thin, glucose-embedded crystals of crotoxin complex kept at -125 degrees C. We show that the camera allows for an on-line assessment of the crystals' crystallinity, flatness, and thickness. Intensities obtained from electron diffraction patterns acquired with the camera have been statistically analyzed and were found to be consistent with theoretically expected values. A quantitative analysis of the diffraction intensity as function of the accumulated electron dose suggests the possibility of recording up to 250 diffraction patterns with 3.5 A resolution from a single crotoxin complex crystal 128 A thick. Tilt series of 125 electron diffraction patterns with 3.5 A data acquired from a single crystal are shown to be practically feasible. The current study demonstrates for the first time the effectiveness of using a slow-scan CCD camera for electron diffraction data collection from thin protein crystals at near atomic resolution. PMID- 7880651 TI - A structure for the signal sequence binding protein SRP54: 3D reconstruction from STEM images of single molecules. AB - The 54-kDa subunit SRP54 of the signal recognition particle in eukaryotic cells is responsible for the recognition of nascent proteins destined for secretion or membrane integration. The three-dimensional structure of this protein was determined using computational techniques applied to images of the molecule obtained via high-resolution, low-dose, scanning transmission electron microscopy at low temperature. The reconstructions at spatial resolutions between 12 and 15 A feature two unequal domains joined by a slender linker. The two-domain structure is in agreement with genetic and biochemical data indicating organization of SRP54 into a larger N-terminal GTP-binding region and a smaller C terminal peptide-binding region. The structure has similarities to other protein domains with related functions and similar amino acid sequences. The larger domain of the 3D reconstruction is consistent in shape and size with the GTP binding domains of EF-Tu and p21-RAS, while the smaller domain is compatible in structure with part of the peptide-binding protein calmodulin. The overall shape of SRP54 and the deduced location of critical functional regions of the molecule provide a structural framework for its known biochemical properties in the targeting cycle of the signal recognition particle. PMID- 7880652 TI - Evaluation of high-resolution shadowing applied to freeze-fractured, deep-etched particles: 3-D helical reconstruction of shadowed actin filaments. AB - Images of shadowed F-actin filaments on mica surfaces obtained using a quick freeze, freeze-fracture, deep-etch technique were subjected to conventional 3-D helical reconstruction methods. Although the shadowing must vary systematically from subunit to subunit, the computed transforms of isolated filaments were characteristic of the helical actin transform. Helical reconstruction was therefore judged to be valid. The theoretical basis for such reconstruction is outlined. The reconstructions showed an average thin (about 3 nm) layer of shadow on the filament surface and both the outer and the inner surfaces of the shadow layer could be visualized. By comparison with the F-actin structure postulated by Holmes et al. (1990) on the basis of the known structure of the actin monomer, it is shown that, at the resolution considered, the inner surface of the shadow provides a reasonably faithful outline of the molecular surface. This, in turn, confirms that the original 3-D structure of the protein molecules has been well preserved throughout the whole preparation procedure up to the final replica. The "shadowed" filaments can thus be correlated axially and azimuthally with known actin structures and, in principle, features such as myosin head location on decorated filaments can be determined. The result emphasizes the amount of detail present in good quality images of shadowed particles and, in this case, shows that detailed evaluation of molecules labeling actin can be made. PMID- 7880653 TI - Three-dimensional membrane crystals in amphibian cone outer segments. 1. Light dependent crystal formation in frog retinas. AB - When frog retinas are exposed to light, a series of three-dimensional crystals develop within the outer segment disk system of cones but not rods. The crystals involve components that span cytoplasmic, disk membrane, and intradisk domains of the outer segment. The crystalline membrane domains are directly continuous with adjacent, noncrystalline lamellar regions. In axial extent, the crystals may involve as few as 1 or 2 disks or as many as 30 disks. However, within each disk, only one crystalline domain typically is observed. Within a crystal, the membranes are more planar in shape and more uniform in axial spacing then adjacent, noncrystalline lamellar regions. Furthermore, as crystalline domains expand laterally, one observes increased axial spacing disorder in noncrystalline lamellar regions, along with an increase in the width of the intradisk compartment. Thus, crystals appear to grow laterally by depleting adjacent lamellar regions of components that influence the normal membrane pair separation and axial spacing of cone outer segment disks. In isolated retinas, the crystalline domains appear to be randomly distributed along the length of the outer segment and show no preference for association with either the closed or open margins of the disk. After 45 min in the light, the crystals occupy approximately 10% of the cone outer segment volume. On the basis of comparative structural, biochemical, and physiological data, cone outer segment crystals may represent a cocrystal between bleached, phosphorylated opsin (providing transmembrane and intradisk elements) and the cytoplasmic protein, arrestin (providing trans-cytoplasmic elements). Thus, crystal formation may provide one mechanism of light adaptation within the cone outer segment. The spontaneous, bleaching-induced formation of these crystals in situ offers the possibility that cocrystals of cone outer segment components can be prepared in vitro for higher resolution crystallographic analyses. PMID- 7880654 TI - Ovarian hyperstimulation syndrome. PMID- 7880655 TI - Comparison of invasive and non-invasive measurement of continuous arterial pressure using the Finapres in patients undergoing spinal anaesthesia for lower segment caesarean section. AB - We have compared arterial pressures measured by an indwelling radial cannula with those obtained non-invasively by the Finapres 2000 (Ohmeda) during spinal anaesthesia for lower segment Caesarean section. The digital outputs of both pressures were recorded using a computerized system. We studied 20 patients, yielding a total of 18,772 data points after elimination of data recorded during arterial flushing and erroneous results from each source. The data analysis demonstrated a normal distribution for differences between the two methods of measurement, and the correlations between invasive and Finapres readings for systolic, diastolic and mean pressures were 0.78, 0.72 and 0.79, respectively, indicating an overall poor reflection of intra-arterial pressure by the Finapres under these circumstances. Some patients and some periods of readings reflected a high degree of precision and little bias. However, unexplained large differences in pressure and trends of change that were out of phase over time occurred frequently. We conclude that the Finapres cannot be recommended as a monitor of arterial pressure in this group of patients in whom sudden hypotension may be a threat to maternal or fetal outcome. PMID- 7880656 TI - Interaction between baricity (glucose concentration) and other factors influencing intrathecal drug spread. AB - The effects of intrathecal injection of 0.5% bupivacaine in solutions containing various concentrations of glucose have been studied in four groups of 20 patients. When solutions containing 0.8% glucose were injected at the L3-4 interspace the median maximum extent of block was higher, and the range of blocks wider, with the 8% solutions. All patients receiving 0.8% glucose had blocks between the T5 and T10 dermatomes, confirming previous work on the benefits of this concentration of glucose. In the two other groups 0.5% bupivacaine containing 0 or 0.8% glucose was injected at the L2-3 interspace. In both groups of patients a wider range of blocks, with a median maximum extent that was higher, was produced. These results demonstrate how glucose concentration may be used to influence the spread of intrathecal solutions and how other factors can obscure the effect of glucose concentration. PMID- 7880657 TI - Comparison of continuous spinal anaesthesia using a 32-gauge catheter with anaesthesia using a single-dose 24-gauge atraumatic needle in young patients. AB - One hundred and twenty-eight ASA I-III patients less than 40 yr of age, undergoing orthopaedic or trauma lower limb surgery, were allocated randomly to receive either continuous spinal anaesthesia (CSA) using a 32-gauge polyimide microcatheter with a permanent stylet (Rusch/TFX Medical, Duluth, GA, USA) or single-dose spinal anaesthesia (SDSA) with a 24-gauge x 103-mm Sprotte spinal needle (Pajunk, Germany). Plain bupivacaine (0.5%) was used as the local anaesthetic. The initial doses were 1 ml (5 mg) of CSA and 3 ml (15 mg) of SDSA, while the re-injection doses were 1 ml (5 mg) in the CSA group. SDSA was quicker to perform: mean 4.4 (SD 1.6) min compared with 6.2 (2.6) min for CSA (P < 0.01). Times to onset and surgical anaesthesia were also significantly greater in the CSA group (P < 0.01). The quality of the block was better in the SDSA group (P < 0.05), but was associated with greater haemodynamic instability (P < 0.05). The segmental level of analgesia was significantly lower in the CSA group (median T10 (range T12-T8)) than in the SDSA group (T9 (T11-T5)) (P < 0.05). There were no significant differences in the incidence of postoperative complications, with two mild spinal headaches in both groups. We conclude that CSA using a microcatheter in young patients is difficult to perform and affords no advantages over SDSA with a small gauge atraumatic needle. PMID- 7880658 TI - Uteroplacental and fetal haemodynamics and cardiac function of the fetus and newborn after crystalloid and colloid preloading for extradural caesarean section anaesthesia. AB - We have studied the effects of randomized preloading with either a crystalloid (lactated Ringer's) 15 ml kg-1 or colloid (hydroxyethyl starch) 7.5 ml kg-1 solution in 20 parturients undergoing elective Caesarean section under extradural anaesthesia, on blood flow in maternal placental and non-placental uterine and placental arcuate arteries and in fetal umbilical, renal and middle cerebral arteries, using a pulsed colour Doppler technique. Simultaneously, fetal and neonatal myocardial function were investigated by pulsed Doppler and M-mode echocardiography. We found no changes in maternal or fetal blood velocity waveform indices after crystalloid preloading, but the pulsatility index of the maternal non-placental uterine artery increased significantly after colloid preloading. Fetal heart rate decreased after preloading with crystalloid solution. There were no differences in fetal or neonatal myocardial function between the groups, and the outcome of the newborn infants were uneventful in all cases. These results suggest that preloading with either a crystalloid or colloid solution may lead to different uterine and fetal haemodynamics but these solutions had only minimal effects on fetal and neonatal myocardial performance and no effect on the clinical condition of newborns in uncomplicated pregnancies. PMID- 7880659 TI - Oral clonidine premedication attenuates the hypertensive response to ketamine. AB - Clonidine diminishes sympathetic nervous system activity via a central action. To test if the haemodynamic responses to ketamine, a centrally acting sympathomimetic drug, are attenuated by clonidine, we studied arterial pressure (AP) and heart rate (HR) changes after ketamine 1 mg kg-1 in 40 normotensive patients undergoing general anaesthesia. They were allocated randomly to receive clonidine 5 micrograms kg-1 and famotidine 20 mg (n = 20) or to a control group (n = 20) which received only famotidine 20 mg orally 90 min before induction of anaesthesia. After administration of ketamine 1 mg kg-1 and vecuronium 0.2 mg kg 1, ventilation of the lungs was controlled with 67% nitrous oxide in oxygen to maintain end-tidal carbon dioxide at 4-4.7 kPa. AP and HR were measured noninvasively at 1-min intervals for 10 min after ketamine. After induction of anaesthesia, AP was increased significantly from resting values in the control group, but remained unchanged in the clonidine group (P < 0.05). Maximum changes in mean AP were also significantly greater in the control group compared with the clonidine group (29.2 (12.8) vs 19.5 (13.1) mm Hg, P = 0.02). However, no change in HR was noted throughout the 10-min study. PMID- 7880660 TI - Prevention of nausea and vomiting with transdermal hyoscine in adults after middle ear surgery during general anaesthesia. AB - In a double-blind, randomized study, we have compared the efficacy of transdermal hyoscine in the prevention of nausea and vomiting with placebo in 60 young, ASA I II patients after middle ear surgery during general anaesthesia. In the placebo group, 27% and 43% of patients suffered from nausea and vomiting, respectively, during the first 24 h after anaesthesia. The corresponding values for both symptoms in the hyoscine group were 10% (P < 0.001 between groups). The frequency of side effects was similar in both groups. The results suggest that transdermal hyoscine is a useful prophylaxis against nausea and vomiting after middle ear surgery. PMID- 7880661 TI - Preoperative or postoperative diclofenac for laparoscopic tubal ligation. AB - We have compared the analgesic effects of diclofenac given before operation or immediately after operation in a randomized, double-blind, double-dummy study of 40 healthy female patients undergoing laparoscopic tubal ligation. Group 1 patients received diclofenac 75 mg as a 3-ml i.m. injection 1-2 h before operation and normal saline 3 ml i.m. immediately after surgery. Group 2 patients received normal saline 3 ml i.m. before operation and diclofenac 75 mg i.m. immediately after surgery. Outcome measures were patients' perception of pain on a visual analogue scale (VAS), verbal response scale (VRS), the number of patients who required postoperative morphine, time to first postoperative morphine injection and total dose of morphine given. VAS at 30 min and at 1, 3 and 6 h after operation were, respectively (median, interquartile range) 4.5 (2.3 6.0) vs 5.3 (2.8-7.8); 3.3 (2.3-5.0) vs 4.4 (3.0-5.8); 1.4 (0-2.3) vs 1.9 (0.8 3.0); 0.5 (0-1) vs 0.7 (0-1.3), (ns). VRS at 1 and 3 h after operation were, respectively, (median, interquartile range) 2.2 (1.5-3.0) vs 2.7 (2.0-4.0) and 0.8 (0-1.3) vs 0.9 (0-1.5) (ns). Sixteen patients in group 1 compared with 17 in group 2 required postoperative morphine. Time to first morphine administration and dose given were, respectively, (median, interquartile range) 50.6 (39-60) min vs 35.7 (20-49) min (P = 0.1) and 9.0 (5-10) mg vs 9.5 (7.5-10) (P = 0.9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880662 TI - Induction of anaesthesia with eltanolone at different rates of infusion in elderly patients. AB - We have determined the effective dose of eltanolone (pregnanolone) required to induce anaesthesia in 30 ASA I and II patients aged 60 yr and over. Eltanolone 4 mg ml-1 was administered at a rate of 300 ml h-1 (group 1), 600 ml h-1 (group 2) or 1200 ml h-1 (group 3) until loss of consciousness, as judged by loss of verbal contact with the patient. Anaesthesia was induced successfully in all patients. The slower rates of induction were associated with a significant increase in induction time (ANOVA, P < 0.01) and a decrease in the induction dose (P < 0.01). There was a significant reduction in systolic arterial pressure after induction of anaesthesia in groups 2 and 3 (MANOVA, P < 0.01). This study suggests that the induction dose of eltanolone in unpremedicated older patients should not exceed 0.6 mg kg-1. PMID- 7880663 TI - Breathing systems: effect of fresh gas flow rate on enflurane consumption. AB - The vaporization rates of enflurane were measured in 412 anaesthetics using appropriate fresh gas flow rates in Bain (12 litre min-1), Magill (6 litre min-1) and circle systems (3 litre min-1, 1 litre min-1 and "closed"). In all patients reducing the fresh gas flow rate resulted in lower enflurane consumption. The percent savings were 18-86% depending on the initial fresh gas flow rate and the size of the change in fresh gas flow. The reduction in enflurane use was more marked in inpatients (long cases) than in day-case patients (short cases). PMID- 7880664 TI - Methylmethacrylate bone cement does not release histamine in patients undergoing prosthetic replacement of the femoral head. AB - This study was designed to see if methylmethacrylate monomer bone cement released histamine in 13 patients undergoing total hip replacement surgery with a cemented prosthesis, compared with seven control patients receiving a cementless porous coated prosthesis. Blood samples for plasma concentrations of histamine were obtained before the start of anaesthesia, immediately before insertion of methylmethacrylate bone cement into the shaft of the femur in the cemented fixation group or before insertion of the femoral component of the prosthesis in the cementless fixation group, and 15, 30 and 60 min after the start of implantation of the prosthesis. In both groups, changes in plasma histamine did not differ significantly from baseline before implantation of cement. There were no significant differences between groups. We conclude that methylmethacrylate bone cement does not release histamine during total hip replacement surgery. PMID- 7880665 TI - Convective warming after hypothermic cardiopulmonary bypass. AB - In a randomized, controlled study, we found that convective warming after hypothermic cardiopulmonary bypass did not accelerate the rate of warming of the body core or the time to tracheal extubation. The relationship between body core and shell temperature, however, was affected. In all patients inadequate time spent rewarming on cardiopulmonary bypass prolonged body core warming time and time to tracheal extubation. Rate of warming of body core was inversely related to body mass index. Convective warming was delivered using BairHugger (Augustine Medical Inc., MN, USA) and Warm Touch (Mallinckrodt Medical UK Ltd, Northampton, UK) blankets. There was no difference between the performance of each blanket when powered by the BairHugger 500 power unit set at its medium setting of 38 degrees C, and when chest drain and radial artery cannulation sites were left exposed for observation. PMID- 7880666 TI - Postoperative throat complaints after tracheal intubation. AB - We have investigated the incidence of throat complaints 6-24 h after tracheal intubation in 1325 patients. Variables such as anaesthetic drug, intubation time, number of intubation attempts, gastric tube, sex and age were recorded. The incidence of sore throat was considerably lower (14.4%) compared with other reports in the literature and was significantly greater in females (17.0% vs 9.0%) and after thyroid surgery. The incidence of sore throat was not increased after multiple intubation attempts or after administration of suxamethonium or a non-depolarizing neuromuscular blocker. PMID- 7880667 TI - Use of ketorolac in the prevention of suxamethonium myalgia. AB - We have evaluated the effect of ketorolac in the prevention of suxamethonium myalgia. Sixty ASA I patients who presented for extraction of wisdom teeth as day cases were allocated randomly to one of three equal groups. Patients received either 0.9% saline (placebo), atracurium 0.05 mg kg-1 i.v. or ketorolac 10 mg i.v., 3 min before induction of anaesthesia. Follow-up postal questionnaires (97% response rate) at 48 h showed no reduction in the incidence of myalgia after ketorolac pretreatment compared with saline. The use of atracurium reduced the incidence of myalgia by 60% (P < 0.001) and the severity of fasciculations (P < 0.001). There was no difference in the severity of fasciculations between the saline and ketorolac groups. Intubating conditions were comparable in the three groups. PMID- 7880668 TI - Comparison of neostigmine-induced recovery with spontaneous recovery from mivacurium-induced neuromuscular block. AB - In 24 ASA I-II adults anaesthetized with thiopentone, fentanyl and nitrous oxide in oxygen, we studied neuromuscular transmission with isometric adductor pollicis monitoring. Patients received mivacurium 0.2 mg kg-1 followed by an infusion lasting at least 60 min and adjusted to maintain twitch height at 1-5%. After termination of the mivacurium infusion, when twitch height spontaneously regained 25% of its control value, the patients were allocated to two groups of 12 patients each. In group NEO patients received neostigmine 40 micrograms kg-1 and atropine 15 micrograms kg-1 and in group SPO neuromuscular transmission was allowed to recover spontaneously. Twitch height was measured every 10 s and train of-four (TOF) (2 Hz) every 3 min. After 15 min, residual force after tetanic stimulation (50 and 100 Hz, 5-s duration (RF50HZ, RF100HZ), 1 min apart) were recorded sequentially. At 15 min, mean TOF ratio was greater in group NEO (0.94 (SEM 0.01)) than in group SPO (0.87 (0.02)) (P < 0.01). All patients in group NEO recovered to a TOF ratio greater than 0.7 after 6 min compared with 15 min in group SPO (P < 0.005). A TOF ratio greater than 0.9 was observed in all patients in group NEO compared with only six in group SPO (P < 0.025). Nevertheless, RF50HZ and RF100HZ did not differ significantly (0.92 (0.01) (group NEO), 0.91 (0.01) (group SPO) and 0.83 (0.02) (group NEO), 0.78 (0.03) (group SPO), respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880669 TI - Prevention of venous air embolism in paediatric neurosurgical procedures performed in the sitting position by combined use of MAST suit and PEEP. AB - We studied 60 children undergoing neurosurgical procedures in the sitting position. Routine monitoring included ECG, pulse oximetry, invasive arterial pressure, in particular mean arterial pressure (MAP), and right atrial pressure (RAP). Children were allocated to two groups. In group B lower body positive pressure and positive end-expiratory pressure (PEEP) were used for preventing venous air embolism (VAE). In this group, antishock trousers (MAST suit) were adjusted in supine children. After induction of anaesthesia, different positions were studied: supine and sitting before MAST suit inflation, sitting with MAST suit inflated up to a pressure of 40 mmHg in the lower compartments and 30 mmHg in the abdominal compartment, and finally a combination of lower body positive pressure and PEEP of 8-10 cm H2O. In group A no MAST suit or PEEP was used. Continuous monitoring of end-tidal carbon dioxide pressure throughout (PE'CO2) was used to detect VAE. In order to evaluate the transmission of pressures from the right atrium to the veins at the base of the skull, jugular bulb venous pressure (JBVP) was measured in 20 patients by retrograde catheterization. The incidence of VAE was compared in the two groups. On placing children into the sitting position, a significant decrease in RAP and JBVP was noted without significant changes in MAP in the two groups. Inflation of the MAST suit induced a dramatic increase in RAP and JBVP, reinforced by addition of PEEP. There was a strong positive relationship between RAP and JBVP. There were no deleterious side effects or differences between the two groups in peroperative blood product requirements or surgical general conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880670 TI - QT dispersion and autonomic function in diabetic and non-diabetic patients with renal failure. AB - We have studied 13 patients with diabetic nephropathy and 13 patients with uraemia of other origin undergoing renal transplantation, and 12 control patients undergoing general surgery. QTc dispersion and maximum QTc interval were calculated from the 12-lead ECG, and cardiovascular autonomic function tests were performed. QTc dispersion was significantly greater in diabetic (mean 100 (SD 37) ms) and non-diabetic (51 (17) ms) uraemic patients than in control patients (29 (10) ms), and it differentiated the groups better than maximum QTc. In diabetic patients, severe autonomic neuropathy was common. In other uraemic patients less severe disturbances in autonomic function were found. In diabetic uraemic patients, increased QTc dispersion and severe autonomic neuropathy may indicate high risk for cardiac arrhythmias. In our opinion, QTc dispersion and autonomic function tests may give valuable information on perioperative risks. PMID- 7880671 TI - In vitro effects of HA-1A (Centoxin) on cytokine production in whole blood from intensive care unit patients. AB - The cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF alpha) have been implicated in the pathophysiology of sepsis and the systemic inflammatory response syndrome (SIRS). The anti-endotoxin antibody, HA-1A (Centoxin), introduced as a treatment for sepsis, was withdrawn because of possible toxicity in some patients. There has been little investigation of the effects of HA-1A on cytokine production. Sixty-one whole blood samples from 15 intensive care unit (ICU) patients with SIRS were incubated for 24 h with HA-1A and concentrations of cytokines determined. Concentrations of IL-6 exceeded those in samples incubated without HA-1A by more than 25% in five patients, of whom four died. One death occurred among 10 patients for whom IL-6 concentrations did not increase (P = 0.03). Incubation with HA-1A did not increase concentrations of IL-1 beta or TNF alpha. HA-1A did not affect cytokine production in whole blood from healthy subjects. HA-1A may induce IL-6 production in whole blood from some ICU patients and this response is associated with increased mortality. Immune therapies for treatment of sepsis and SIRS require careful evaluation of their ability to affect cytokine production, before they are introduced for general use. PMID- 7880672 TI - Effects of etomidate on whole-cell and single L-type calcium channel currents in guineapig isolated ventricular myocytes. AB - We have investigated the effects of etomidate 4.4 mumol litre-1, 1.0 mg litre-1 and 27.4 mumol litre-1, 6.25 mg litre-1 on whole-cell and single L-type calcium channel currents in myocytes from guineapig ventricles. For whole-cell recordings, the cells were voltage-clamped and step depolarizations were applied from holding potential of -40 mV to various potentials to elicit L-type calcium currents. Peak calcium currents were decreased significantly by both low and high concentrations of etomidate. Ethanol in the same concentration with the highest etomidate solution (1.1 mmol litre-1) had no significant effect on calcium currents. When single calcium channel activity was investigated, the high concentration of etomidate significantly decreased the open probability of the channel with little or no effect on channel conductance. Mean closed time was increased significantly, caused apparently by prolongation of the slower of two exponential components fitted to histograms of the closed times. The mean open time was virtually unaffected. The low concentration of etomidate did not significantly affect single channel kinetics. These results showed that etomidate decreased L-type calcium current by altering the kinetics of the channel to favour the closed state without any significant change in conductance. However, compared with other anaesthetics which were investigated previously in our laboratory, the overall effect on calcium current appeared to be small. PMID- 7880673 TI - Inhalation anaesthetic competition at high-affinity cocaine binding sites in rat brain synaptosomes. AB - We have shown previously that inhalation anaesthetics inhibit dopamine transport in rat synaptosomes. In order to determine if this inhibition is associated with occupancy of the cocaine site, we examined binding of [3H] (2 beta-carbomethoxy-3 beta-(4-fluorophenyl)-tropane) (3H-CFT) in the presence of halothane or isoflurane 0.01-5 mmol litre-1 in rat brain synaptosomes. Both anaesthetics inhibited 3H-CFT binding (mean Ki 0.61 (SEM 0.12) and 0.75 (0.21) mmol litre-1, respectively), by increasing Kd (13.8 (0.6) and 29.8 (12.8) nmol litre-1, respectively) compared with control (8.02 (0.5) nmol litre-1) (P < 0.01). Halothane did not change Bmax, but isoflurane increased it significantly. Cocaine protected CFT sites from N-ethylmaleimide alkylation, but neither anaesthetic did. Photoaffinity labelling with halothane significantly inhibited 3H-CFT binding compared with UV-exposed controls. We conclude that clinically relevant concentrations of both anaesthetics inhibit high-affinity CFT binding, and the data suggest overlapping sites for halothane and CFT. PMID- 7880674 TI - Effects of halothane and isoflurane anaesthesia on microcirculatory blood flow in musculocutaneous flaps. AB - Hypoperfusion and necrosis in musculocutaneous flaps used for reconstruction of tissue defects is still a significant clinical problem. Although the causes of hypoperfusion are frequently surgical in nature, little is known about the effects of anaesthetic management on blood flow in flaps or the outcome of flap surgery. We compared in minipigs the effects of halothane and isoflurane anaesthesia in equipotent doses on microcirculatory blood flow (MBF) in the skin and muscle part of musculocutaneous flaps and also in intact (control) skin and muscle. Measurements were made during stable normovolaemic conditions and during mild to moderate hypovolaemia (withdrawal of 5%, 10% and 15% of total blood volume). Multi-channel laser Doppler flowmetry (LDF) was used to measure MBF and electromagnetic flowmetry (EMF) for total flap blood flow. During normovolaemic conditions there was no significant difference between the two groups in central haemodynamic or respiratory data. After 15% blood loss, however, there was a significant decrease in mean arterial pressure and cardiac output in the halothane group while there was no significant change in the isoflurane group (P < 0.05). MBF in control skin, control muscle and flap muscle remained approximately 10-15% higher in the isoflurane than in the halothane group throughout the study. In the isoflurane group, MBF in flap skin was unchanged during normovolaemia and there was less than 10% decrease during hypovolaemia. In the halothane group hypovolaemia caused a significant decrease in MBF in flap skin: 27% decrease after 5% blood loss, 45% decrease after 10% blood loss and 49% decrease after 15% blood loss compared with 5%, 20% and 21%, respectively, in intact skin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880675 TI - Withdrawal forces during removal of lumbar extradural catheters. AB - After performing successful continuous lumbar extradural conduction block, we investigated the effects of the extradural insertion technique (midline (M) or paramedian (P)) and patient position during extradural catheter removal (flexed lateral (L) or sitting (S)) on the force required to remove extradural catheters. One hundred parturients were allocated randomly to four groups: ML, MS, PL, PS. The results indicated that neither the midline nor paramedian approach affected withdrawal forces. However, more than 2.5 times as much force was required to remove the catheters when patients were in the flexed sitting compared with the lateral position (P < 0.005). For ease of removal of catheters from the lumbar extradural space we therefore strongly recommend the flexed lateral position. PMID- 7880676 TI - Leg elevation compared with Trendelenburg position: effects on autonomic cardiac control. AB - We have studied in 12 healthy male volunteers the effects of three different body positions (10 degrees head-down tilt, horizontal supine and supine with 50-cm leg elevation from the hip) on the spectral components of heart rate and finger plethysmographic amplitude variability. We have demonstrated the absence of any statistically significant difference in any measure of variability in the time of frequency domain for both of these measures between the three positions. We conclude that neither leg elevation nor 10 degrees head-down tilt is associated with any significant alteration in the dominant parasympathetic cardiac control in comparison with the resting supine position. PMID- 7880677 TI - Hyperventilation-induced unconsciousness during labour. AB - We report the development of unconsciousness caused by hyperventilation in an otherwise healthy woman in labour. Extradural analgesia resulted in restoration of full consciousness and normal respiratory state. The pathophysiology of hyperventilation and aspects of respiratory physiology in pregnancy are discussed. PMID- 7880678 TI - Reversal of post-reperfusion coagulopathy by protamine sulphate in orthotopic liver transplantation. AB - We report details of two liver transplant procedures in which post-reperfusion coagulopathy was reversed by administration of protamine sulphate. Both procedures were uncomplicated until about 30 min after reperfusion of the graft, when the cut surfaces began to ooze blood. Failure of coagulation was confirmed by thrombelastography and in both cases routine coagulation tests revealed a prolonged kaolin cephalin clotting time (KCT). A heparin-like effect was suspected. Protamine sulphate 50 mg was given i.v., resulting in cessation of bleeding and normalization of the thrombelastogram and KCT. PMID- 7880679 TI - Patient-controlled analgesia using a miniature electrochemically driven infusion pump. AB - We describe a miniature electrochemically driven, wrist-worn infusion pump. Generation of gas by an electrolytic reaction compresses a reservoir containing medication and provides a predictable and controllable infusion rate. The pump was used for patient-controlled analgesia (PCA) in women who required analgesia after Caesarean section. It was accepted readily and was convenient for both patients and nursing staff. This portable system, using a novel motive force, has advantages of convenience over larger systems and has sophisticated features not present in existing small systems. It has potential as a routine PCA device and it may have uses in other situations requiring convenient infusion or intermittent injection in an ambulatory setting. PMID- 7880680 TI - A brief historical review of non-anaesthetic causes of fires and explosions in the operating room. AB - Fires and explosions have occurred in the operating theatre for many years. Flammable inhalation anaesthetic agents were responsible for many incidents in the past, but these are no longer available in many countries. Other causes of fires and explosions still exist in the operating theatre and, from time to time, result in serious and occasionally fatal injury. Flammable gastrointestinal gases have been the cause of injury to patients during gastric surgery, laparoscopy and during examination of the large bowel with electrical instrumentation. Gases formed in the bladder during urological procedures have ignited, causing rupture. Alcohol-based skin cleaning agents have resulted in severe burns to the skin. Equipment used for storage and delivery of oxygen to patients has caused fires in a variety of ways. Adhesive skin drapes have resulted recently in two tragic deaths. The increasing use of laser therapy, particularly in ear, nose and throat surgery, and in oral surgery, has brought about a renewed awareness of the risk of fire. The relevant factors which should be borne in mind and the precautions which should be adopted when laser therapy is to be used in the airway are discussed. PMID- 7880681 TI - Consensus statement on red cell transfusion. Proceedings of a Consensus Conference Held by the Royal College of Physicians of Edinburgh, May 9-10, 1994. PMID- 7880682 TI - Tracheal intubation without neuromuscular block. PMID- 7880683 TI - Nitrous oxide uptake and elimination. PMID- 7880684 TI - Speed of onset of sensory block for elective extradural caesarean section. PMID- 7880685 TI - Anaesthetic simulators. PMID- 7880686 TI - Overfill testing of anaesthetic vaporizers. AB - We tested six anaesthetic vaporizers with keyed filler adaptors to see if it was possible to overfill them. For those vaporizers which could be overfilled, the maximum level of overfill was determined and the effect of overfilling on the vaporizer output concentration was measured. Three of the vaporizers, the TEC 4, PPV Mk 1 and MIE Vapamasta 5, could be overfilled. In the case of the TEC 4 and PPV vaporizers, overfilling by more than 100 ml caused a large increase in the vaporizer output concentration. Overfilling the Vapamasta 5 by this amount caused the output concentration to decrease. PMID- 7880687 TI - Accuracy of subject and author indexes in five anaesthesia journals. AB - To determine the accuracy of subject and author indexes in five anaesthesia journals we examined all 1989 and 1991 volumes of Anesthesia and Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anaesthesia and European Journal of Anaesthesiology, and counted the number of entries and the number of errors in both indexes. The number of errors was expressed as a percentage of the number of entries, and the incidences of errors were compared by chi-square contingency table tests. The overall error rate in both indexes and for both years (1989 and 1991) differed significantly among the five journals (P < 0.001). Many of the individual differences were also significant. British Journal of Anaesthesia had the lowest error rate (0.9%), followed by Anesthesia and Analgesia (2.4%), Anesthesiology (3%), European Journal of Anaesthesiology (2.9%) and Canadian Journal of Anaesthesia (11.4%). The combined index accuracy was improved from 1989 to 1991 for Anesthesia and Analgesia, British Journal of Anaesthesia and Canadian Journal of Anaesthesia, did not change for European Journal of Anaesthesiology and was worse for Anesthesiology. PMID- 7880688 TI - Effective absorption of nitrogen dioxide with soda lime. PMID- 7880689 TI - Myotonic dystrophy and target-controlled propofol infusions. PMID- 7880690 TI - Fires and explosions. PMID- 7880691 TI - Impressions of British anaesthesia. PMID- 7880692 TI - Mishap or negligence. PMID- 7880693 TI - Effect of nabilone on nausea and vomiting. PMID- 7880694 TI - Effect of nabilone on nausea and vomiting. PMID- 7880695 TI - Positive lumbar extradural pressure. PMID- 7880696 TI - Echocardiography and chest trauma. PMID- 7880697 TI - Low and high frequency stimulation tests to characterize the effects of edrophonium on vecuronium-induced neuromuscular block. AB - We recorded adductor pollicis mechanical activity in response to low (0.1 and 2 Hz) and high (50 and 100 Hz) frequency stimulation 15 min after edrophonium 250, 500 and 1000 micrograms kg-1, given to antagonize vecuronium-induced block at 10, 25 and 50% pre-reversal twitch height. We studied 54 ASA class I and II anaesthetized (methohexitone, fentanyl, nitrous oxide) young adult patients allocated randomly to nine groups of six patients each. The greater sensitivity of train-of four (TOF) ratio and residual force after 100-Hz, 5-s tetanic stimulation (RF100) to residual deficit allowed discrimination more readily between the effects of edrophonium dose and pre-reversal twitch height (P < 0.001, two-way analysis of variance). The highest reversal scores (approximately 0.9 TOF ratio and 0.6 RF100) were obtained when edrophonium 500-1000 mg kg-1 was given at 50% twitch height (P < 0.05, Duncan's test). PMID- 7880698 TI - Pulmonary function and head lift during spontaneous recovery from pipecuronium neuromuscular block. AB - We have studied in seven healthy conscious volunteers the correlation between the electromyographic (EMG) and clinical criteria used to identify adequate recovery from sub-paralysing doses of pipecuronium. Pipecuronium (mean dose 1.88 (range 0.92-3.16) mg) was administered to reach a T4/T1 ratio of 0.5; full recovery to 1.0 was produced in a mean time of 25.3 (14-39) min. During recovery from neuromuscular block, we measured tidal volume, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) negative inspiratory pressure (NIP), peak expiratory flow rate (PEFR), mid-expiratory flow rate (MEFR) and 5-s head lift. The assessments were started when the train-of-four (TOF) ratio reached 0.5 +/- 0.001 and repeated at each 0.1 +/- 0.001 increase up to a ratio of 1.0. All volunteers showed ptosis and diplopia after the first dose and difficulty in swallowing with subsequent doses. They also experienced a pleasant, relaxing sedative sensation. All could sustain head lift for 5 s at a TOF ratio of 0.5 and higher, except for one subject who could not lift his head only at a ratio of 0.5. There was a statistically significant decrease in FVC, FEV1 and PEFR with a nonsignificant decrease in other pulmonary measurements, except for NIP which only decreased significantly at a ratio of 0.5. These changes are probably of no clinical importance. All the measured respiratory variables returned to control values at a TOF ratio of 0.9. PMID- 7880699 TI - Recovery characteristics after early administration of anticholinesterases during intense mivacurium-induced neuromuscular block. AB - The time course of recovery after early administration of anticholinesterases during intense mivacurium-induced block was evaluated by recording the mechanomyographic response of the adductor pollicis to post-tetanic count (PTC) and train-of-four (TOF) ulnar nerve stimulation. Seventy-two adult patients receiving thiopentone, fentanyl, nitrous oxide, isoflurane anaesthesia and mivacurium 0.15 mg kg-1 were allocated randomly to one of six equal groups according to the type of anticholinesterase and intensity of block at which antagonism was attempted. Groups 1, 3 and 5 received neostigmine 0.07 mg kg-1, while groups 2, 4 and 6 received edrophonium 1 mg kg-1. At the time of administration of antagonist there was no response to PTC in groups 1 and 2, a PTC of 1 or more was detectable in groups 3 and 4 and the first twitch of the TOF (T1) had recovered to 10% in the conventional antagonism groups (5 and 6). The longest clinical duration (CD) values (time from administration of mivacurium to T1 25%) were encountered in groups 1, 5 and 6 and were 17.4 (7.9), 19.7 (3.4) and 21.4 (4.8) min, respectively. CD was reduced significantly in groups 2, 3 and 4 and values were 13.9 (3.5), 13.7 (3.5) and 13.8 (3.3) min, respectively. Recovery indices (RI) (time interval between T1 25% and 75%) were 13.8 (7.3), 6.3 (1.4), 4.6 (1.8), 6.0 (2.1), 3.7 (2.2) and 4.8 (3.1) min in groups 1-6, respectively and was prolonged with neostigmine antagonism at PTC 0 (group 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880701 TI - Anaesthesia and the undergraduate medical curriculum. PMID- 7880700 TI - Dose-response studies of the interaction between mivacurium and suxamethonium. AB - We have determined the effect of pretreatment with mivacurium on the potency of suxamethonium and the effect of prior administration of suxamethonium on the potency of mivacurium. We studied 100 ASA I or II patients during thiopentone fentanyl-nitrous oxide-isoflurane anaesthesia. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to train-of-four stimulation of the ulnar nerve (2 Hz at 12-s intervals). Single dose-response curves were determined by probit analysis. Pretreatment with mivacurium had a marked antagonistic effect on the development of subsequent depolarizing block produced by suxamethonium. The dose-response curves for suxamethonium alone and after pretreatment with mivacurium did not deviate from parallelism, but those constructed after mivacurium were shifted significantly to the right (P < 0.0001). The calculated doses producing 50% depression of T1 (ED50) were 86 (95% confidence intervals 83-88) and 217 (208-225) micrograms kg-1 for suxamethonium alone and after mivacurium, respectively. This study also demonstrated that prior administration of suxamethonium did not appear to influence either the slope of the regression lines or the potency of mivacurium. Combining the results of this study with a previous study (mivacurium ED50 = 20.8 (20.3-21.3) micrograms kg-1 during isoflurane-nitrous oxide anaesthesia), we suggest that the potency of mivacurium did not differ from that observed after suxamethonium (17.4 (16.9 17.9) micrograms kg-1). PMID- 7880702 TI - Effectiveness and sequelae of very low-dose suxamethonium for nasal intubation. AB - We have studied the effectiveness and sequelae of low-dose suxamethonium in 60 day-case oral surgery patients requiring nasal intubation. Anaesthesia was induced with propofol and alfentanil; 60 patients were allocated randomly to three groups of 20 patients and received no suxamethonium, suxamethonium 0.25 mg kg-1 or 0.5 mg kg-1. All patients received i.v. fentanyl and diclofenac 100 mg rectally for analgesia. Good intubating conditions were produced in all 20 patients receiving suxamethonium 0.25 mg kg-1, in 19 patients receiving suxamethonium 0.5 mg kg-1 and in 11 patients not receiving a neuromuscular blocker. The incidence of postoperative myalgia after suxamethonium 0.25 mg kg-1 (20%) did not differ significantly from the incidence after propofol and alfentanil alone (28%). PMID- 7880703 TI - Comparison of extradural fentanyl, bupivacaine and two fentanyl-bupivacaine mixtures of pain relief after abdominal surgery. AB - Fentanyl 50 micrograms, bupivacaine 50 mg and two mixtures containing fentanyl 50 micrograms and bupivacaine 25 mg or 12.5 mg (0.25 and 0.125%), respectively, in a volume of 10 ml were administered via thoracic extradural catheters to 24 patients after major abdominal surgery. All patients received all four treatments, in a randomized order, so that each patient received one of the 24 possible combinations of the four treatments. Pain relief was assessed by a linear analogue pain scale and the Prince Henry Hospital pain score. The duration of pain relief, effects on ventilatory frequency, heart rate, arterial pressure and central venous pressure were also recorded. Mean reductions in the analogue pain scale for fentanyl, bupivacaine, and fentanyl in 0.25% and 0.125% bupivacaine were 80 (SEM 5) %, 87 (4) %, 86 (5) % and 77 (5) %, respectively (ns). Pain scores decreased by 62 (6) %, 83 (5) %, 77 (6) % and 72 (6) %, respectively (ns). Mean arterial pressure decreased to 90 (2) %, 70 (2) %, 81 (2) % and 82 (3) %, respectively, of pretreatment values. In this respect, bupivacaine alone was significantly different from the three other treatments (P < 0.001). Hypotension (reduction in arterial pressure greater than 25% of pretreatment mean arterial pressure) was also more frequent after bupivacaine alone (P < 0.01). Effects on ventilation, heart rate and central venous pressure did not differ between the four treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880704 TI - Spread of subarachnoid hyperbaric amethocaine in adolescents. AB - We have compared the spread of subarachnoid hyperbaric amethocaine in adolescents with that in adults. Amethocaine 8 mg in 2 ml of 10% glucose was injected through a 25-gauge spinal needle inserted at the L3-4 interspace in 21 adolescents aged 12-16 yr and in 111 adults aged 17-82 yr. Although we found no differences in height, weight or body mass index between the adolescents and adults, maximum spread of analgesia was significantly higher in the adolescents (median T3 (range T4-C5) than in the adults (T4 (T9-C7)). We conclude that subarachnoid injection of hyperbaric amethocaine produces an unexpectedly higher level of analgesia in adolescents than in adults. PMID- 7880705 TI - Propofol pharmacokinetics in children with biliary atresia. AB - We studied the pharmacokinetics of an i.v. bolus dose of propofol 2.5-3.0 mg kg-1 in eight children (age 4-24 months) with biliary atresia and in six control (ASA I) children (age 11-43 months). Blood samples were obtained for 4 h after administration of propofol. Blood concentrations of propofol were measured by high pressure liquid chromatography. Systemic clearance of propofol (CI) and volume of distribution at steady state (Vss) showed a highly significant correlation with body weight. Propofol CI and Vss, normalized for body weight, were similar in children with biliary atresia (mean 37.5 (SD 8.3) ml min-1 kg-1 and 3.5 (1.6) litre kg-1, respectively) compared with control children (38.7 (6.8) ml min-1 kg-1 and 2.4 (0.8) litre-1 kg-1, respectively). We conclude that in children with biliary atresia the pharmacokinetics of propofol are similar to those of healthy children. PMID- 7880706 TI - First-pass pulmonary retention of sufentanil at three different background blood concentrations of the opioid. AB - Using a double-indicator technique, we have studied, in 10 patients undergoing aorto-coronary bypass surgery, first-pass pulmonary retention of sufentanil. Pulmonary retention was studied at three pseudo steady-state background blood concentrations of 2.8 (0.66), 6.9 (1.2) and 15.9 (2.6) ng ml-1, respectively, produced by a computer-controlled infusion. Mean first-pass pulmonary retentions at these concentrations were 68 (95% confidence intervals 62-73), 65 (60-70) and 60 (52-67)%, respectively. First-pass pulmonary retention of sufentanil was significantly lower at the highest background concentration compared with the lowest background concentration. First-pass pulmonary retention of sufentanil was partly saturable in the range of concentrations used for clinical purposes. PMID- 7880707 TI - Degradation products of sevoflurane during low-flow anaesthesia. AB - Low-flow (1 litre min-1) sevoflurane anaesthesia was used in 16 patients undergoing laparoscopic cholecystectomy (group LSC, n = 8) or tympanoplasty (group TP, n = 8), and concentrations of sevoflurane degradation products were measured. Degradation products in the circuit were measured hourly, and end-tidal carbon dioxide concentration, inspired and end-tidal sevoflurane concentrations, and carbon dioxide elimination were monitored. The only degradation product detected was CF2=C(CF3)-O-CH2F (compound A). The mean maximum concentrations of compound A were 21.6 (SEM 1.6) ppm and 19.6 (0.8) ppm in the LSC and TP groups, respectively (ns). The maximum temperatures of soda lime were 46.4 (0.5) degrees C and 44.8 (0.5) degrees C, respectively (P < 0.05). Hourly end-tidal sevoflurane concentrations and concentrations of sevoflurane degradation products were the same for both groups. Carbon dioxide elimination was the same for both groups 1 h after the start of anaesthesia, but was higher in group LSC after 2 h (P < 0.05). Intraperitoneal carbon dioxide insufflation associated with laparoscopic cholecystectomy had no effect on the concentration of sevoflurane degradation products. PMID- 7880708 TI - Pharmacodynamic effects of 51W89, an isomer of atracurium, in children during halothane anaesthesia. AB - 51W89 is one of the 10 stereoisomers of atracurium with less propensity to release histamine than atracurium. We evaluated dose-response data and neuromuscular effects of 2 x ED95 dose and maintenance doses of 51W89 during halothane anaesthesia in 68 children, 2-12 yr old. Neuromuscular function was monitored by evoked adductor pollicis EMG. Log-probit, single-dose, dose-response data gave ED50 and ED95 values of 23 and 41 micrograms kg-1, respectively, for 51W89. Twice the ED95 dose (80 micrograms kg-1) had an onset time (time from administration to maximum effect) of 2.5 (SD 0.8) min, a clinical duration (time to 25% EMG recovery) of 31 (7) min and a recovery index (time from 25 to 75% EMG recovery) of 11.1 (1.7) min. Seventy-nine incremental doses of 51W89 of 94 (19) micrograms kg-1. Duration of effect of incremental doses remained constant within individuals reflecting non-cumulative properties. There were insignificant changes in arterial pressure and heart rate after 51W89 and no side effects were observed. We regard 51W89 as a promising, non-cumulative, intermediate-acting neuromuscular blocking agent the effects of which can be antagonized easily by neostigmine. PMID- 7880709 TI - Haemodynamic and catecholamine responses to induction of anaesthesia and tracheal intubation in diabetic and non-diabetic uraemic patients. AB - We have studied cardiovascular and catecholamine responses to induction of anaesthesia and tracheal intubation in 13 patients with diabetic nephropathy, in 12 patients with uraemia of other origin and in 12 ASA I control patients. All uraemic patients were undergoing renal transplantation. Cardiovascular autonomic function tests indicated that severe autonomic neuropathy was common in the diabetic patients; less severe impairment of autonomic function was found in the non-diabetic uraemic patients. The systolic pressor response to intubation was greater in diabetic uraemic patients than in the other groups (P < 0.05). Both uraemic groups had higher plasma catecholamine concentrations than the ASA I patients both before and after induction of anaesthesia. The increased plasma concentrations of catecholamines in the uraemic patients may be a result of impaired clearance of catecholamines and higher sympathoadrenal activity needed to maintain cardiac function. The normal systolic pressor response to tracheal intubation in the uraemic patients indicates that the capacity of the cardiovascular system to respond to a stressful stimulus was preserved in these patients also, in spite of autonomic neuropathy. The greater response in the diabetic group may be caused by increased sensitivity to catecholamines and loss of autonomic control. PMID- 7880710 TI - Arterial pressure control with isoflurane using fuzzy logic. AB - Arterial pressure is still one of the most important measures in estimating the required dose of inhaled anaesthetics. It is measured easily and reacts rapidly which makes it suitable as a variable for feedback control of depth of anaesthesia. Fuzzy logic, a novel approach to feedback control, was used to control arterial pressure in 10 patients during intraabdominal surgery by automatic adjustment of the concentration of isoflurane in fresh gas. During anaesthesia, fuzzy control periods of 45-min duration were alternated randomly with human control periods of equal duration. During the skin incision period (-3 to + 12 min) 48.2% of all fuzzy control pressure values were within +/- 10% of the desired mean arterial pressure compared with 40.4% of the human control values (P < 0.05). The corresponding values for the remainder of the operation were 78.3% and 83.2%, respectively. Thus fuzzy out-performed human control at skin incision, but was slightly inferior during the rest of the operation. We conclude that fuzzy logic is a promising new technique for control of isoflurane delivery during routine anaesthesia. PMID- 7880711 TI - Actions of morphine on noradrenaline efflux in the rat locus coeruleus are mediated via both opioid and alpha 2 adrenoceptor mechanisms. AB - A recent report showed that morphine inhibited [3H]clonidine binding to human platelet alpha 2 receptors. As the analgesic effects of morphine and clonidine are clinically additive, we investigated the possibility that morphine might stimulate alpha 2 receptors or alpha 2 mechanisms in rat locus coeruleus (LC) slices. Stimulated LC noradrenaline efflux was measured by fast cyclic voltammetry. Cumulatively applied morphine 10(-8)-10(-4) mol litre-1 had no effect on noradrenaline efflux evoked by pseudo-single-pulse stimulations (20 pulses at 100 Hz) while the alpha 2 agonist dexmedetomidine 2 x 10(-10)-10(-7) mol litre-1 decreased efflux of noradrenaline in a concentration-dependent manner. Administration of single concentrations of morphine 10(-6)-10(-4) mol litre-1 significantly decreased efflux of noradrenaline (by 22% and 17%, respectively) and attenuated the effect of dexmedetomidine in a concentration dependent fashion. Morphine 10(-6)-10(-4) mol litre-1 also decreased efflux of noradrenaline on long stimulus trains (50 pulses at 50 Hz). These data suggest that the analgesic potentiation of alpha 2 and opioid agonists is not mediated via LC alpha 2 receptors. PMID- 7880712 TI - Selective effects of ketamine on amino acid-mediated pathways in neonatal rat spinal cord. AB - Many ion channels have been proposed as target sites for anaesthetic action; for some agents multiple receptors-ion channels may be implicated. In addition to acting as a non-competitive antagonist at glutamate NMDA receptors, ketamine also affects other ion channels. The present study was undertaken to determine if the effects of ketamine in an integrated portion of the central nervous system involve multiple actions at glutamate non-NMDA, glutamate NMDA, and GABAA receptor. The effects of ketamine 1-50 mumol litre-1 were examined on three pharmacologically distinct responses in isolated superfused neonatal rat spinal cord: the monosynaptic reflex (glutamate non-NMDA); a slow ventral root potential (VRP) with a large NMDA-mediated component; and the dorsal root potential (DRP) (GABAA). Ketamine, at concentrations relevant to anaesthesia (1-50 mumol litre 1), reversibly depressed the area under the curve of the slow VRP in a concentration-dependent fashion. The effects of ketamine were selective for the early (0-1 s) component of the slow VRP. The monosynaptic reflex was unaffected at these concentrations. The actions of ketamine resembled those of the NMDA antagonist APV. Dorsal root potentials evoked by dorsal root stimulation or by muscimol were either unaffected or reversibly depressed by ketamine 1-20 mumol litre-1. The concentrations tested include the anaesthetic range for both rats and humans. The effects of ketamine on neurotransmission in this preparation can be accounted for entirely by its action at NMDA receptors. Glutamate non-NMDA receptors were unaffected and GABAA transmission was not enhanced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880713 TI - Determination of anaesthetic agent concentration by refractometry. AB - Reference refractivity values have been derived for the anaesthetic agents halothane, isoflurane, enflurane, sevoflurane and desflurane which are traceable to national measurement standards. A simple method and equation have been derived for the application of these data to the measurement of agent concentration by refractometry. The main instrumental sources of uncertainty associated with this method are discussed and their respective contributions quantified. Agent concentration can be measured routinely at the +/- 1% level of uncertainty using this approach. PMID- 7880714 TI - Auditory disturbance associated with interscalene brachial plexus block. AB - We performed an audiometric study in 20 patients who underwent surgery of the shoulder region under an interscalene brachial plexus block (IBPB). Bupivacaine 0.75% with adrenaline was given followed by a 24-hr continuous infusion of 0.25% bupivacaine. Three audiometric threshold measurements (0.25-18 kHz) were made: the first before IBPB, the second 2-6 h after surgery and the third on the first day after operation. In four patients hearing impairment on the side of the block was demonstrated after operation, in three measurements on the day of surgery and in one on the following day. The frequencies at which the impairment occurred varied between patients; in one only low frequencies (0.25-0.5 kHz) were involved. The maximum change in threshold was 35 dB at 6 kHz measured at the end of the continuous infusion of bupivacaine. This patient had hearing threshold changes (15-20 dB) at 6-10 kHz on the opposite side also. IBPB may cause transient auditory dysfunction in the ipsilateral ear, possibly via an effect on sympathetic innervation. PMID- 7880715 TI - Effect of magnesium on coagulation as measured by thrombelastography. AB - Magnesium has long been assumed to have anticoagulant properties, but the effect has been poorly quantified. The thrombelastograph (TEG) was used to evaluate the effect of magnesium using blood from volunteers. Magnesium sulphate was added to one blood sample and another sample was used as a control. Both samples were tested simultaneously and the results evaluated against the magnesium concentration measured in each sample. At serum magnesium concentrations < 3 mmol litre-1, there were no significant effects of magnesium. With increasing magnesium concentrations there was a statistically significant but small prolongation of the r time, k time and r + k time. Maximum amplitude was affected only at magnesium concentrations > 7 mmol litre-1. Magnesium has only minimal effects on coagulation which are unlikely to be clinically important. PMID- 7880716 TI - Anesthetic management of a 656-g neonate undergoing pulmonary valvotomy. AB - We describe the successful management of a 656-g preterm infant of 29 weeks' postconceptional age undergoing closed transventricular pulmonary valvotomy. The patient had a critical pulmonary stenosis and was treated with an infusion of prostaglandin E1, which resulted in excessive pulmonary blood flow through the ductus arteriosus. The key points in anaesthetic management were maintaining an optimum balance between the systemic and pulmonary circulation and preparing for the abrupt haemodynamic change caused by valvotomy. PMID- 7880717 TI - Physiological determination of cerebrovascular reserves and its use in clinical management. AB - Cerebrovascular reserve (CVR) can be assessed by measuring the hemodynamic response to a physiological stress such as alteration of blood pressure, increase in tissue acidosis, lowered oxygen supply, increase in metabolic demand, or occlusion of an artery. Failure of the cerebrovascular system to maintain function or normative values of several interrelated hemodynamic variables- cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO2),--in response to a stress implies a compromise of the normally robust compensatory mechanisms. The conclusions that are possible from this information depend on the type of stress induced and the technology used to measure the response. Technologies that permit a rapid test-retest format coupled with a physiological stress provide the most direct information about the hemodynamics of cerebrovascular territories. Patients whose cerebral vasculature becomes compromised by any of a broad range of disorders and who, thus, are at increased risk for stroke now can be readily identified based upon evidence of exhausted CVR. Strategies for treating hemodynamically driven disorders also can now be designed based upon such patient specific CVR information. It is hoped that integration of CVR into the standard clinical assessment of patients with occlusive vascular disorders (OVD) will lead to treatments that focus not only on the previously understood embolic causes of stroke, but also on the often interrelated hemodynamic factors. PMID- 7880718 TI - Cytokines, inflammation, and brain injury: role of tumor necrosis factor-alpha. AB - The cytokine tumor necrosis factor (TNF-alpha) is a pleotrophic polypeptide that plays a significant role in brain immune and inflammatory activities. TNF-alpha is produced in the brain in response to various pathological processes such as infectious agents [e.g., human immunodeficiency virus (HIV) and malaria], ischemia, and trauma. TNF-alpha mRNA is rapidly produced in response to brain ischemia within 1 h, reaches a peak at 6-12 h post ischemia, and subsides 1-2 days later. TNF-alpha mRNA expression corresponds in a temporal fashion to other cytokines such as interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (KC), and IL-1 and precedes the infiltration of inflammatory cells into the injured zone. TNF-alpha is present early in neuronal cells in and around the ischemic tissue (penumbra), yet at later time points, the peptide is found in macrophages in the infarcted tissue. TNF-alpha has been demonstrated to cause expression of proadhesive molecules on the endothelium, which results in leukocyte accumulation, adherence, and migration from capillaries into the brain. Furthermore, TNF-alpha activates glial cells, thereby regulating tissue remodeling, gliosis, and scar formation. Thus, evidence is emerging in support of a role for TNF-alpha in injury induced by infectious, immune, toxic, traumatic, and ischemic stimuli. TNF-alpha promotes inflammation by stimulation of capillary endothelial cell proinflammatory responses and thereby provides leukocyte adhesion and infiltration into the ischemic brain. The evidence generated so far suggests that agents that suppress TNF-alpha's production or actions will reduce leukocyte infiltration into ischemic brain regions and thereby diminish the extent of tissue loss. PMID- 7880719 TI - Antisense oligonucleotides directed against p53 have antiproliferative effects unrelated to effects on p53 expression. AB - Antisense oligonucleotides targeting p53 have been hailed as a potentially new technique for treating patients with cancer, and there have been encouraging reports of good patient tolerance in vivo and of antiproliferative effects in vitro. However, evidence is lacking that these oligonucleotides are acting via an antisense interaction to modulate p53 expression. We examined a phosphorothioate antisense oligonucleotide, directed against exon 10 of the TP53 gene, and a chimaeric phosphorothioate-phosphodiester oligonucleotide directed against the p53 translation initiation codon. Both failed to specifically suppress p53 protein production in a cell-free assay system or to have any effect on mutant p53 expression by human pancreatic cancer cell lines. Antiproliferative effects were apparent, especially with the phosphorothioate antisense oligonucleotide, but this was independent of the p53 status of the cells (mutant, wild-type or absent) and also occurred with the control (sense and randomised) oligonucleotides. The most dramatic antiproliferative effects were seen with the 'control' phosphorothioate oligonucleotides. These findings suggest that the antiproliferative effects of some antisense oligonucleotides may be unrelated to expression of the gene they have been designed to target. PMID- 7880720 TI - Association of genetic alterations on chromosome 17 and loss of hormone receptors in breast cancer. AB - To investigate possible relationships between genetic alterations and hormonal deregulation during breast cancer development and/or progression, we examined 616 primary breast cancers for loss of heterozygosity (LOH) at chromosomal regions 16q24, 17p13.3 and 17q21, and for amplifications of the ERBB2 and c-MYC loci. A comparison of oestrogen receptor (ER) and progesterone receptor (PgR) status in tumour cells with data concerning these genetic alterations revealed that LOH at 17q21 was significantly correlated with absence of oestrogen receptors (ER) (P < 0.0003) or progesterone receptors (PgR) (P < 0.0001), and with the absence of both (P < 0.0001). Similarly, a significant association was observed between amplification of ERBB2 and the absence of either ER or PgR. LOH at 17p13.3 was associated with the absence of PgR (P < 0.01). These data suggest a possible relationship between specific genetic changes on chromosome 17 and hormonal deregulation in the progression of breast cancer. PMID- 7880722 TI - Loss of heterozygosity of the oestrogen receptor gene in breast cancer. AB - DNA from 67 primary breast carcinoma biopsies has been examined for loss of heterozygosity (LOH) using the microsatellite (TA)n repeat marker positioned 1 kb upstream of the oestrogen receptor (ER) gene. Forty-seven (70.1%) of the cases were informative; nine of these (19.1%) were positive for LOH. In three of the nine cases, there was total loss, and in the other six cases there was a marked reduction in the intensity of signal from one allele. LOH correlated weakly with histological grade and age, but not with ER status. This result suggests that LOH of the ER gene does not have an important role in the lack of ER function in breast cancer tissues. PMID- 7880721 TI - Human breast cancer cells contain a phosphoramidon-sensitive metalloproteinase which can process exogenous big endothelin-1 to endothelin-1: a proposed mitogen for human breast fibroblasts. AB - Endothelin-1 (ET-1) levels are elevated in human breast tumours compared with normal and benign tissues, and in the presence of insulin-like growth factor 1 (IGF-I) ET-1 is a potent mitogen for human breast fibroblasts. In this study we have examined the ability of intact human breast cancer cell lines to process exogenously added big ET-1 (1-38) to the active mature ET-1 peptide by using a specific radioimmunometric assay. In both hormome-dependent (MCF-7, T47-D) and hormone-independent (MDA-MB-231) breast cancer cell lines the putative endothelin converting enzyme (ECE) exhibited apparent Michaelis-Menten kinetics when converting added big ET-1 to ET-1. Both basal ET-1 production and exogenously added big ET-1 to ET-1 conversion were greatly reduced in all three cell lines in response to the metalloproteinase inhibitor phosphoramidon but were insensitive to other classes of protease inhibitors. Inhibition was also observed when cells were incubated in the presence of the divalent cation chelators 1,10 phenanthroline and EDTA. In MCF-7 cells the optimal pH for the ECE activity using a saponin cell permeabilisation procedure was found to residue within a narrow range of 6.2-7.26. Our results indicate that human breast cancer cells contain a neutral phosphoramidon-sensitive metalloproteinase which can process big ET-1 to ET-1. In the breast this conversion could contribute substantially to the local extracellular levels of this proposed paracrine breast fibroblast mitogen. PMID- 7880723 TI - A germline TaqI restriction fragment length polymorphism in the progesterone receptor gene in ovarian carcinoma. AB - Clinical outcome in ovarian carcinoma is predicted by progesterone receptor status, indicating an endocrine aspect to this disease. Peripheral leucocyte genomic DNAs were obtained from 41 patients with primary ovarian carcinoma and 83 controls from Ireland, as well as from 26 primary ovarian carcinoma patients and 101 controls in Germany. Southern analysis using a human progesterone receptor (hPR) cDNA probe identified a germline TaqI restriction fragment length polymorphism (RFLP) defined by two alleles: T1, represented by a 2.7 kb fragment; and T2, represented by a 1.9 kb fragment and characterised by an additional TaqI restriction site with respect to T1. An over-representation of T2 in ovarian cancer patients compared with controls in the pooled Irish/German population (P < 0.025) was observed. A difference (P < 0.02) in the distribution of the RFLP genotypes between Irish and German control populations was also observed. The allele distributions could not be shown to differ significantly from Hardy Weinberg distribution in any subgroup. Using hPR cDNA region-specific probes, the extra TaqI restriction site was mapped to intron G of the hPR gene. PMID- 7880724 TI - Detection of necrosis in human tumour xenografts by proton magnetic resonance imaging. AB - Tumours with necrotic regions have an inadequate blood supply and are expected to differ from well-vascularised tumours in response to treatment. The purpose of the present work was to investigate whether proton magnetic resonance imaging (MRI) might be used to detect necrotic regions in tumours. MR images and histological sections from individual tumours of three different amelanotic human melanoma xenograft lines (BEX-t, HUX-t, SAX-t) were analysed in pairs. MRI was performed at 1.5 T using two spin-echo pulse sequences, one with a repetition time (TR) of 600 ms and echo times (TEs) of 20, 40, 60 and 80 ms and the other with a TR of 2000 ms and TEs of 20, 40, 60 and 80 ms. Spin-lattice relaxation time (T1), spin-spin relaxation time (T2) and proton density (N0) were calculated for each volume element corresponding to a pixel. Synthetic MR images, pure T1, T2 and N0 images and spin-echo images with chosen values for TR and TE were generated from these data. T1, T2 and N0 distributions of tumour subregions, corresponding to necrotic regions and regions of viable tissue as defined by histological criteria, were also generated. T1 and T2 were significantly shorter in the necrotic regions than in the regions of viable tissue in all tumours. These differences were sufficiently large to allow the generation of synthetic spin-echo images showing clear contrast between necrosis and viable tissue. Maximum contrast was achieved with TRs within the range 2800-4000 ms and TEs within the range 160-200 ms. Necrotic tissue could also be distinguished from viable tissue in pure T1 and T2 images. Consequently, the possibility exists that MRI might be used for detection of necrotic regions in tumours and hence for prediction of tumour treatment response. PMID- 7880725 TI - Loss of expression and loss of heterozygosity in the DCC gene in neoplasms of the human female reproductive tract. AB - In order to identify the possible role of the DCC gene in neoplasms of the human female reproductive tract, messenger RNA expression of the DCC gene was examined by reverse transcriptase-polymerase chain reaction, and expression of the DCC gene product was detected immunohistochemically. While histologically normal endometrium, cervical epithelium and ovary expressed detectable mRNA of the DCC gene, three of eight (37%) endometrial carcinomas, one of two (50%) cervical carcinomas and 9 of 22 (41%) ovarian malignant tumours had significantly reduced or negligible DCC expression, and another endometrial carcinoma and two other ovarian tumors underexpressed DCC when compared with histologically normal endometrial or ovarian tissues. Impaired DCC mRNA expression was detected more frequently in grade 3 ovarian epithelial tumours than in grade 1 tumours (P = 0.002). Loss of expression of the DCC gene product detected by immunohistochemistry significantly correlated with the loss of mRNA expression in ovarian carcinomas (P = 0.01 by chi-square test) or in both endometrial and ovarian carcinomas combined (P = 0.001). Loss of heterozygosity of the DCC gene was also evaluated by restriction fragment polymorphism analysis of the polymerase chain reaction-amplified DNA fragment. Loss of heterozygosity of the DCC gene was detected in one of seven (14%) informative cases of endometrial carcinomas, 1 of 11 (9%) informative cases of cervical carcinomas and two of six (33%) informative cases of ovarian tumours. These results demonstrate that inactivation of the DCC gene, especially by the loss of expression, plays a significant role in the aetiology of neoplasms of the human reproductive tract. PMID- 7880726 TI - Prognostic significance of the c-erbB-2 oncogene product in childhood medulloblastoma. AB - The expression and prognostic significance of the c-erbB-2 oncogene product was studied in 55 cases of childhood medulloblastoma. Forty-six of the 55 tumours (83.6%) expressed the c-erbB-2 product. The percentage of tumour cells expressing the c-erbB-2 product proved to be a significant indicator of patient outcome when analysed as both a categorical and a continuous variable. As a categorical variable, patients with more than 50% positive tumour cells had a significantly worse survival, with only 10% alive at 10 years vs 48% for those with less than 50% positive tumour cells (log rank P = 0.0049). To demonstrate that this observed prognostic significance was both independent and not a result of 'data driven' categorisation, it was also entered into the Cox model as a continuous variable. Prognostic significance was retained in P = 0.038. PMID- 7880727 TI - The cytotoxic activity of Taxol in primary cultures of tumour cells from patients is partly mediated by Cremophor EL. AB - In patient tumour samples the activity in vitro of Taxol corresponded fairly well to the known clinical activity and Taxol showed low cross-resistance to standard cytotoxic drugs. However, the Taxol solvent Cremophor EL--ethanol was considerably active alone, whereas paclitaxel formulated in ethanol was less active. Taxol thus seems to contain two components active against patient tumour cells in vitro. PMID- 7880728 TI - Pharmacology of liposomal vincristine in mice bearing L1210 ascitic and B16/BL6 solid tumours. AB - Vincristine pharmacokinetic, tumour uptake and therapeutic characteristics were investigated here in order to elucidate the processes underlying the enhanced efficacy observed for vincristine entrapped in small (120 nm) distearoylphosphatidylcholine/cholesterol liposomes. Plasma vincristine levels after intravenous (i.v.) injection are elevated more than 100-fold in the liposomal formulation compared with free drug in tumour-bearing as well as non tumour-bearing mice over 24 h. Biodistribution studies demonstrate that the extent and duration of tumour exposure to vincristine is dramatically improved when the drug is administered i.v. in liposomal form. Specifically, 72 h trapezoidal area under the curve values for liposomal vincristine in the murine L1210 ascitic and B16/BL6 solid tumours are 12.9- to 4.1-fold larger, respectively, than observed for free drug. Similar to previous results with the L1210 model, increased drug delivery to the B16 tumour results in significant inhibition of tumour growth, whereas no anti-tumour activity is observed with free vincristine. Comparisons of drug and liposomal lipid accumulation in tumour and muscle tissue indicate that the enhanced efficacy of liposomal vincristine is related predominantly to drug delivered by liposomes to the tumour site rather than drug released from liposomes in the circulation. Consequently, improvements in liposomal vincristine formulations must focus on factors that increase uptake of liposomes into tumour sites as well as enhance liposomal drug retention in the circulation. PMID- 7880730 TI - Cisplatin sensitivity and thermochemosensitisation in thermotolerant cDDP sensitive and -resistant cell lines. AB - Development of thermotolerance is an important phenomenon that must be considered when thermochemotherapy with multiple heat treatments is used clinically. To study the effect of thermotolerance on cellular cisplatin (cDDP) sensitivity at 37 degrees C and 43 degrees C in cell lines with different cDDP sensitivities, two Ehrlich ascites tumour cell lines (one with high cDDP sensitivity and one with in vitro acquired cDDP resistance) were used. The results indicate that in both cell lines the state of thermotolerance per se did not affect the cDDP sensitivity at 37 degrees C. Thus, general elevations in 'all' heat shock protein levels as found in thermotolerant cells apparently do not influence cDDP sensitivity to a considerable extent. The sensitising effect of a (second) heat treatment given simultaneously with a cDDP treatment was less in thermotolerant cells. Thermal enhancement ratios (TERs) at the 10% survival level for heat doses of 43 degrees C for 30 min or 43 degrees C for 60 min were reduced by a factor of 1.6 and 2.1 in cDDP-resistant and -sensitive thermotolerant cells respectively, as compared with control cells. Thus, protection against heat damage in thermotolerant cells seems to be paralleled by diminished thermal chemosensitisation. Although the effect of thermotolerance on the cDDP sensitising effect was less pronounced in the resistant cells, a modifying effect on the resistance factor was not achieved. PMID- 7880729 TI - Mechanisms of resistance to combinations of vincristine, etoposide and doxorubicin in Chinese hamster ovary cells. AB - We have isolated from Chinese hamster ovary cells, 30 sublines resistant to vincristine, doxorubicin or etoposide and 43 sublines evading treatment with a pair of these drugs. Isolated in one step and under low selective pressure, sublines were 3- to 25-fold more resistant to their selecting drug(s) than the parental cells. Possible P-glycoprotein-associated multidrug resistance was investigated through pgp gene copy number and mRNA expression level. DNA topoisomerase II alteration was evaluated from the ability of nuclear extracts to form cleavable complexes. Vincristine (all sublines) and doxorubicin (6/7 sublines) preferentially selected for pgp gene amplification and mRNA overexpression, whereas selection with etoposide resulted in a decrease of cleavable complex formation in 11 out of 13 sublines. A common pgp gene-mediated resistance was found in the 13 doxorubicin plus vincristine-selected sublines, whereas all but one of the 12 etoposide plus vincristine-resistant sublines displayed both pgp mRNA overexpression and decreased ability to form cleavable complexes. Among the 18 doxorubicin plus etoposide selected sublines, five exhibited a decreased ability to form cleavable complexes only, six exhibited pgp mRNA overexpression only and six exhibited both alterations. Overall, drug resistance could not be attributed to either mechanism in three of the 73 sublines. We conclude that under low selective pressure it is possible to find a combination of drugs which require simultaneous selection of more than one resistance mechanism; such cells emerge with very low frequency. PMID- 7880731 TI - Different vimentin expression in two clones derived from a human colocarcinoma cell line (LoVo) showing different sensitivity to doxorubicin. AB - We selected two clones, isolated from the human colocarcinoma cell line LoVo, showing a sensitivity to doxorubicin similar to (LoVo clone 5) or three times lower than (LoVo clone 7) the parental cell line. Since vimentin was atypically expressed in a human breast carcinoma cell line made resistant to doxorubicin, we looked at vimentin expression in these two clones with spontaneously different sensitivity to the drug. For comparison we used the parental cell line LoVo WT and LoVo/DX made resistant pharmacologically. mRNA for vimentin was undetectable by Northern blot analysis in LoVo WT and in LoVo clone 5, while expression of this gene was high in LoVo clone 7 and in LoVo/DX. This increase in mRNA levels was not related to an amplification of DNA, as suggested by Southern blot analysis. Immunofluorescence and immunocytochemistry findings confirmed, at protein level, the mRNA data. In LoVo clones 5 and 7, there were respectively 8.6% and 71% vimentin-positive cells, although the two clones showed similar expression of multidrug resistance gene 1 (mdr-1) and accumulated intracellular doxorubicin at similar levels. Similarly, drug efflux was the same for both clones. Our results show for the first time that cells resistant to doxorubicin express vimentin independently of the mdr glycoprotein. However when cells from clone 5 were transfected with human vimentin cDNA, they did not become resistant, indicating that vimentin can be considered as a marker of resistance in these cells but does not give rise to a resistant phenotype by itself. PMID- 7880732 TI - Current sample handling methods for measurement of platinum-DNA adducts in leucocytes in man lead to discrepant results in DNA adduct levels and DNA repair. AB - DNA adduct levels were measured with atomic spectroscopy in white blood cells (WBCs) from patients with solid tumours who were treated with six weekly courses of cisplatin. In 21 patients (I) the WBCs were collected after thawing frozen whole-blood samples according to a previously described method. In 32 other patients (II) WBCs were collected immediately after blood sample collection. The two methods for WBC collection were also compared in vitro. The maximal DNA adduct levels in vivo after the first course were in I 2.48 +/- 1.14 and in II 1.28 +/- 0.40 pg of platinum per microgram of DNA (P < 0.0001). The DNA 'repair' in the first course (DNA adduct level at the end of the infusion minus the level 15 h post infusion) was in I 40% +/- 29% and in II 18% +/- 29% (P = 0.009). These differences were consistent in all measured courses. In vitro, the DNA adduct levels in the freshly prepared WBCs were significantly lower at 0, 1 and 4, but not 24 h, after start of the incubation with cisplatin than in the WBCs collected after freezing and thawing the blood sample. The same experiment with carboplatin in vitro also resulted in significantly lower adducts in freshly isolated WBCs. The higher DNA adduct levels and DNA 'repair' in I are caused by remaining unbound cisplatin in the sample tubes, which can form DNA adducts ex vivo. The same results in vivo can be anticipated when carboplatin is used. PMID- 7880733 TI - Antitumoral efficacy and pharmacokinetic properties of pirarubicin upon hepatic intra-arterial injection in the rabbit V x 2 tumour model. AB - To improve the efficiency of hepatic intra-arterial (h.i.a.) chemotherapy, we selected pirarubicin (THP) because it shows good properties for h.i.a. chemotherapy, such as fast and efficient cellular uptake, and used it for h.i.a. chemotherapy in rabbits with V x 2 tumour implanted in the liver. The anti-tumour effect of THP upon h.i.a. administration was compared with that upon intravenous (i.v.) injection and also with the anti-tumour activity of epirubicin (EPI) upon h.i.a. injection using optimal and maximal tolerated doses of each drug. When tumour growth rates and morphometric examinations were evaluated, it was found that THP and EPI were effective against V x 2 tumour when injected via the h.i.a. route. The activity of THP was stronger than that of EPI. As regards h.i.a. injection-related complication, plasma transaminase levels were temporarily elevated. To demonstrate higher anti-tumour activity and other advantages of h.i.a. injection of THP, plasma and tumour drug concentrations were determined by high-performance liquid chromatography after THP or EPI was administered at an equal dose to the rabbit V x 2 model. Hepatic intra-arterial injection of THP accomplished a selective and higher uptake into the tumour and lower effusion into the plasma than i.v. injection of THP or h.i.a. injection of EPL. Our findings indicate that THP is the better candidate of the two drugs tested for the h.i.a. chemotherapy because of its greater anti-tumour activity and the lower systemic drug exposure achieved upon h.i.a. injection. PMID- 7880734 TI - Successful local regional therapy with topotecan of intraperitoneally growing human ovarian carcinoma xenografts. AB - The therapeutic effects of intraperitoneal topotecan, a water-soluble camptothecin analogue, were investigated in two models of human ovarian carcinoma xenografted intraperitoneally into nude mice: the IGROV-1 tumour, which originated from an untreated patient, and the A2780 tumour, selected for resistance in vitro to cisplatin (A2780DDP). In IGROV-1 tumour-bearing mice, the optimal dose (10 mg kg-1) of topotecan, given intraperitioneally every 4 days for four occasions markedly increased survival time over control mice (300 T/C%) and cured 4/9 mice, and such effects were not achieved by any of the clinically available drugs tested, i.e. cisplatin carboplatin and doxorubicin delivered intraperitonally according to their optimal doses and schedules. In the treatment of A2780DDP tumour-bearing mice, topotecan was very effective since, at dose levels of 6.6 and 10 mg kg-1 every 4 days for four occasions, 15/18 mice survived more than 100 days, and most of them (12/15) were found to be tumour free. The high responsiveness of this tumour to topotecan might be related to the elevated expression of the target enzyme topoisomerase I. From these results, intraperitoneal treatment with topotecan appears to be a promising approach in the therapy of refractory ovarian cancer confined to the peritoneal cavity. PMID- 7880735 TI - Detection of hypoxia by measurement of DNA damage in individual cells from spheroids and murine tumours exposed to bioreductive drugs. I. Tirapazamine. AB - The possibility of using tirapazamine (SR 4233) to identify hypoxic cells in multicell spheroids and murine tumours was examined by measuring tirapazamine induced DNA damage to individual cells from multicell spheroids and SCCVII murine tumours. Fluorescence microscopy and image analysis were used to measure the extent of migration of DNA from individual cells embedded in agarose and exposed to an electric field. Using both the alkaline and neutral versions of the comet assay, at least 20 times more single-strand breaks were observed in cells from fully anoxic than fully oxic Chinese hamster V79 spheroids exposed to 30 microM tirapazamine, and about 10 times more single- than double-strand breaks were observed. Cells from spheroids containing about 50% radiobiologically hypoxic cells showed a pattern of tirapazamine breaks which translated to approximately 30% well-oxygenated in SCCVII tumors growing in C3H mice was also demonstrated. Cells close to tumour blood vessels showed less DNA damage by 20 mg kg-1 tirapazamine than cells distant from blood vessels. Rejoining of single-strand breaks was exponential, with a half-time of about 1 h under aerobic conditions, but rejoining half-time increased to 2 h for cells allowed to repair under anoxic conditions. While tirapazamine damage to DNA measured using the comet assay cannot provide a direct measure of hypoxic fraction, the degree of heterogeneity in DNA damage can be used to estimate the range and distribution of individual cell oxygen contents within spheroids and tumours. PMID- 7880736 TI - Detection of hypoxia by measurement of DNA damage in individual cells from spheroids and murine tumours exposed to bioreductive drugs. II. RSU 1069. AB - The ability of the dual-function bioreductive drug, RSU 1069, to identify hypoxic cells in multicell spheroids and murine SCCVII squamous cell carcinomas was examined using the alkaline comet method. This method applies fluorescence microscopy and image analysis to measure the amount of migration of DNA from individual cells embedded in agarose and exposed to an electric field. Chinese hamster V79 spheroids, exposed for 1 h to RSU 1069, were disaggregated and individual cells were analysed for DNA damage. Following exposure to RSU 1069, aerobic cells exhibited DNA single-strand breaks while DNA interstrand cross links were produced in hypoxic cells. Spheroids containing 40-50% radiobiologically hypoxic cells exhibited 20-30% cells with cross-links and the remainder showed only strand breaks. Similar patterns of damage were observed in SCCVII tumours growing in C3H mice exposed to 25-200 mg kg-1. Subsequent irradiation of cells in vitro greatly improved the distinction between aerobic and hypoxic cells from spheroids or SCCVII murine tumours exposed to RSU 1069, especially after treatment with low drug doses. The pattern of damage was relatively stable for at least 4 h after drug injection. Results indicate that detection of hypoxic cells in solid tumours may be practical using this agent or a prodrug, PD 144872, selected for phase I clinical testing as a hypoxic cell radiosensitiser and cytotoxin in human tumours. PMID- 7880737 TI - Establishment of a new human extrahepatic bile duct carcinoma cell line (OCUCh LM1) and experimental liver metastatic model. AB - A new human extrahepatic bile duct carcinoma cell line, designated OCUCh-LM1, was established from a liver metastatic lesion in a 61-year-old male. OCUCh-LM1 cells proliferated in a monolayered sheet with a population doubling time of 31 h. OCUCh-LM1 cells had an aneuploid pattern with a DNA index of 1.76, and chromosome counts showed a unimode of 63. OCUCh-LM1 cells expressed various carbohydrate antigens, including sialyl Lewis X, carbohydrate antigen 19-9 and SPan-1 antigen. Subcutaneous injections of OCUCh-LM1 cells induced tumour formation in nude mice. The reconstituted tumours were classified as well-differentiated adenocarcinoma. A daughter line, designated OCUCh-LM1-H1, was also established from liver metastatic colonies induced by splenic injection of OCUCh-LM1. OCUCh-LM1-H1 cells showed a higher potential for liver metastasis than OCUCh-LM1 (100% vs 20%). Since OCUCh-LM1 retains the initial characteristics (as of 93 passages at present) and expresses various carbohydrate antigens, the OCUCh-LM1 cell line and liver metastatic model established here will be useful for the study of the biological nature of extrahepatic bile duct carcinoma and the relationship between the expression of carbohydrate antigens and metastatic potential. PMID- 7880738 TI - Induction of immune cell infiltration into murine SCCVII tumour by photofrin based photodynamic therapy. AB - Cellular populations in the squamous cell carcinoma SCCVII, growing in C3H/HeN mice given Photofrin, were examined at various time intervals during the photodynamic light treatment and up to 8 h later. Cell populations present within excised tumours were identified by monoclonal antibodies directed against cell type-specific membrane markers using a combination of the indirect immunoperoxidase and Wright staining or by flow cytometry. Photofrin-based photodynamic therapy (PDT) induced dramatic changes in the level of different cellular populations contained in the treated tumour. The most pronounced was a rapid increase in the content of neutrophils, which increased 200-fold within 5 min after the initiation of light treatment. This was followed immediately by an increase in the levels of mast cells, while another type of myeloid cells, most likely monocytes, invaded the tumour between 0 and 2 h after PDT. The examination of cytolysis of in vitro cultured SCCVII tumour cells mediated by macrophages harvested from the SCCVII tumour revealed a pronounced increase in the tumoricidal activity of tumour-associated macrophages isolated at 2 h post PDT. It seems, therefore, that the PDT-induced acute inflammatory infiltration of myeloid cells into the treated tumour is associated with functional activation of immune cells. PMID- 7880739 TI - Constitutive expression of the c-H-ras oncogene inhibits doxorubicin-induced apoptosis and promotes cell survival in a rhabdomyosarcoma cell line. AB - Drugs used in anti-cancer chemotherapy are thought to exert their cytotoxic action by induction of apoptosis. Genes have been identified which can mediate or modulate this drug-induced apoptosis, among which are c-myc, p53 and bcl-2. Since expression of oncogenic ras genes is a frequent observation in human cancer, we investigated the effects of the c-H-ras oncogene on anti-cancer drug-induced apoptosis. Apoptosis induced by a 2 h doxorubicin exposure was measured by in situ nick translation and flow cytometry in a rat cell line (R2T24) stably transfected with the c-H-ras oncogene and in a control cell line (R2NEO) transfected only with the antibiotic resistance gene neo. Both cell lines (R2T24 and R2NEO) had nearly identical growth characteristics, including cell doubling time, distribution over the cell cycle phases and plating efficiency in soft agar. Doxorubicin exposure of the R2NEO cells led to massive induction of apoptosis. In contrast, R2T24 cells, expressing the c-H-ras oncogene, showed significantly less apoptosis after doxorubicin incubation. Doxorubicin induced approximately 3- to 5-fold less cytotoxicity in the R2T24 cells than in the R2NEO cells, as determined by clonogenic assay in soft agar. No difference was observed in intracellular doxorubicin accumulation between the two cell lines, indicating that the classical, P-glycoprotein-mediated multidrug resistance phenotype is not involved in the observed differences in drug sensitivity. In conclusion, our data show that constitutive expression of the c-H-ras oncogene suppresses doxorubicin induced apoptosis and promotes cell survival, suggesting that human tumours with ras oncogene expression might be less susceptible to doxorubicin treatment. PMID- 7880740 TI - Increasing the susceptibility of the rat 208F fibroblast cell line to radiation induced apoptosis does not alter its clonogenic survival dose-response. AB - Recent studies have suggested a correlation between the rate and incidence of apoptosis and the radiation response of particular cell lines. However, we found that increasing the rate of induction of apoptosis in the fibroblast line 208F, by transfecting it with human c-myc, did not lead to a change in its clonogenic survival dose-response for either gamma-irradiation or 125I-induced DNA damage. It was also found that expression of mutant (T24) Ha-ras in the 208F line appeared to decrease the level of apoptosis per mitosis after irradiation and inhibited the formation of nucleosomal ladders, but did not affect either the onset of the morphological features of apoptosis or the clonogenic survival dose response of the cells to either gamma-irradiation or 125I-induced DNA damage. Our findings suggest that it may be incorrect to make predictions about the radiosensitivity of cells based only on knowledge of their mode of death. PMID- 7880741 TI - Cellular fibronectin in serum and plasma: a potential new tumour marker? AB - The concentration of cellular fibronectin (cFN) containing the extra domain A (EDA) was measured in 479 plasma and 300 serum samples from healthy blood donors by a competitive enzyme immunoassay (EIA). Serum and plasma samples contained low concentrations of EDAcFN. The mean concentration of EDAcFN was higher in plasma (2.46 mg l-1) than in serum (0.30 mg l-1). No significant differences between sexes or age groups were found. The EDAcFN concentrations were also measured in 120 patients with various malignancies. The mean values in serum were 4.28 mg l 1, 2.01 mg l-1 and 5.18 mg l-1 in patients with digestive tract malignancies, breast cancer and a group of miscellaneous cancers respectively. In plasma, the corresponding values were 12.26 mg l-1, 4.38 mg l-1 and 11.12 mg l-1 respectively. The serum EDAcFN concentration was higher than the 97.5th percentile level of healthy blood donors in 86% of patients with digestive tract and in 76% with miscellaneous malignancies. In patients with breast cancer 60% had elevated levels of EDAcFN. The corresponding figures for plasma samples in patients with digestive tract and miscellaneous malignancies were 79% and 71% respectively. In patients with breast cancer only 30% had elevated plasma levels of EDAcFN. The mean values in serum and plasma of 20 patients with benign diseases were below the cut-off levels. Consistent with the EIA results, Western blotting revealed increased amounts of EDAcFN in blood samples from cancer patients. Pregnancy did not affect the EDAcFN concentration. The mean values in 20 pregnant women were below the cut-off levels. PMID- 7880742 TI - Adjuvant chemotherapy for oesophagogastric cancer with epirubicin, cisplatin and infusional 5-fluorouracil (ECF): a Royal Marsden pilot study. AB - Previous trials of adjuvant chemotherapy for oesophagogastric cancer have shown only modest or no improvement in survival. However, the regimens used in these studies produce low response rates in patients with advanced disease. ECF is a new regimen which results in higher response rates and may therefore be more effective in the adjuvant setting. Twenty-nine patients who had undergone a potentially curative resection for oesphagogastric carcinoma were treated with ECF [epirubicin 50 mg m-2 and cisplatin 60 mg m-2 for 18 weeks]. The median age was 52.5 years. Three patients had oesophageal tumours, 14 had tumours of the oesophagogastric junction (OGJ) and 12 had gastric tumours. All were adenocarcinomas apart from one undifferentiated carcinoma. One patient had stage I disease, nine stage II, 17 stage II and two stage IV. The mean number of chemotherapy cycles per patient was 5.2 (range 2-8). The median follow-up was 8.4 months (1.5-36.3 months). Eleven patients relapsed during follow-up (38%). One patient had an anastomotic recurrence and ten patients distant metastases. Overall 3 year survival was 61.5% (95% confidence interval 42-79); 3 year survival in stage II was 50% (21.2-86.3) and in stage III 65.6% (40-86). Chemotherapy was well tolerated, with grade 3/4 toxicity as follows: leucopenia 13.5%, nausea and vomiting 10%, diarrhoea 3.5%, infection 3.5% and thrombocytopenia 3.5%. There were no treatment-related deaths. We conclude that ECF can be administered safely as adjuvant treatment to patients with surgically resected gastro-oesophageal carcinoma. The results, especially in patients with stage III disease, are encouraging and support the investigation of this regimen within a prospective randomised trial. PMID- 7880743 TI - Psychological distress in head and neck cancer patients 7-11 years after curative treatment. AB - Long-term survivors of head and neck cancer may suffer from psychological distress and reduced quality of life because of late side-effects of the treatment. In a follow-up study of patients randomised to two different radiation fractionating regimens, 204 patients filled in a mailed questionnaire 7-11 years after treatment. The questionnaire consisted of the General Health Questionnaire, 20-item version (GHQ-20), and the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30). There were no differences in psychological distress between patients receiving conventional radiotherapy and those receiving a slightly hypofractionated regimen. A high prevalence of psychological distress was found in both treatment groups (30% of 'cases' according to the GHQ-20), especially in patients with impaired cognitive or social function, or with pain. Clinicians need to be aware of this morbidity, and their ability to detect patients with psychological problems needs to be improved. The GHQ-20 can facilitate the communication process in a clinical setting. With an increased awareness of these problems and by using valid instruments for identification of patients at risk, the clinicians may intervene and help the patients to reduce their psychological distress. PMID- 7880744 TI - Factors affecting platinum concentrations in human surgical tumour specimens after cisplatin. AB - We assessed factors which affect cisplatin concentrations in human surgical tumour specimens. Cisplatin 10 mg m-2 was given i.v. to 45 consenting patients undergoing surgical resection of neoplasms, and platinum was assayed in resected tumour and in deproteinated plasma by flameless atomic absorption spectrophotometry. By multiple stepwise regression analysis of normalised data, patient characteristics that emerged as being most closely associated (P < 0.05) with tumour platinum concentrations (after correcting for associations with other variables) were tumour 'source' [primary brain lymphomas, medulloblastomas and meningiomas ('type LMM') > 'others' > lung cancer > head/neck cancer > gliomas) or tumour 'type' (LMM > brain metastases > extracerebral tumours > gliomas), serum calcium and chloride (positive correlations) and bilirubin (negative). Tumour location (intracranial vs extracranial) did not correlate with platinum concentrations. If values for a single outlier were omitted, high-grade gliomas had significantly higher platinum concentrations (P < 0.003) than low-grade gliomas. For intracranial tumours, the computerised tomographic scan feature that correlated most closely with platinum concentrations in multivariate analysis was the darkness of peritumoral oedema. Tumour source or type is a much more important correlate of human tumour cisplatin concentrations than is intracranial vs extracranial location. Serum calcium, chloride and bilirubin levels may affect tumour cisplatin uptake or retention. CT scan characteristics may help predict cisplatin concentrations in intracranial tumours. PMID- 7880745 TI - Intra-arterial chemotherapy in patients with breast cancer: a feasibility study. AB - The aim of this study was to assess the practicality of treating patients with various stages of breast cancer by means of regional (intra-arterial) chemotherapy. Three groups of patients received a median of four (range 2-4) cycles of combination chemotherapy: group I operable primary (n = 10); group II, locally advanced disease (n = 20); group III, recurrent locoregional disease (n = 22). The response rates (complete response, partial response and mixed response) in these groups of patients were 100% in groups I and II and 86% in group III. Morbidity included drug streaming and dysaesthesia in the hand. Patients in groups I and II had their tumours downstaged, allowing surgery to be performed. Local control was also achieved in group III when other treatment modalities had failed. PMID- 7880747 TI - Accumulation of natural killer cells after hepatic artery embolisation in the midgut carcinoid syndrome. AB - Eleven patients with disseminated midgut carcinoid tumour disease were subjected to hepatic artery embolisation. In six patients, lymphocytosis with a predominance of NK cells occurred and the cytotoxic activity of isolated lymphocytes increased. A relation between NK cell accumulation and subsequent radiological and biochemical response was observed, and it is suggested that anti tumour mechanisms other than ischaemia may contribute to the therapeutic response in these patients. PMID- 7880746 TI - Level of expression of E-cadherin mRNA in colorectal cancer correlates with clinical outcome. AB - A series of colorectal carcinomas (n = 49) resected from patients with known clinical outcomes were analysed for E-cadherin expression using in situ hybridisation to measure mRNA. Patients surviving 5 years or longer (n = 31) exhibited significantly higher levels of E-cadherin mRNA than those surviving less than 5 years (n = 18, P = 0.003). These preliminary results from this small sample suggest that E-cadherin expression may be a useful prognostic marker in colorectal cancer patients. PMID- 7880748 TI - Cisplatin, vincristine and ifosphamide combination chemotherapy of metastatic seminoma: results of EORTC trial 30874. EORTC GU Group. AB - The aims of the trial were to establish the response rate and determine the toxicity of combination chemotherapy with ifosphamide, vincristine and cisplatin (HOP regimen) in advanced metastatic seminoma and to study the role of post chemotherapy consolidation treatment. Patients with bulky metastatic non-alpha fetoprotein-producing seminomas were eligible for this phase II study [serum human chorionic gonadotropin < 200 U l-1 (< 40 ng l-1)] if they presented with abdominal masses > or = 10 cm or had extra-gonadal seminoma or had relapsed after previous radiotherapy. The HOP regimen consisted of four 3-weekly cycles of the following drug combination: ifosphamide (days 1-5, 1.2 mg m-2 day-1), vincristine (day 1, 2 mg) and cisplatin (days 1-5, 20 mg m-2 day-1). Residual masses persisting 6 months after chemotherapy could be considered for consolidation surgery or radiotherapy. Maximal response to the HOP chemotherapy (evaluated at any time) was based on the WHO criteria. The median observation time was 2.5 years (range 1.8-5.5 years). Thirteen institutions treated 42 eligible patients within the study (testicular cancer stage > or = IID, 25; extragonadal, 5; relapse after previous radiotherapy, 12). Two patients were not evaluable for response owing to premature treatment discontinuation. Maximal response was as follows: complete remission (CR), 26 (65%); partial remission (PR) 11 (28%); no change (NC), 2 (5%); progressive disease (PD), 1 (3%). Four patients have died, three from their malignancy (two without previous irradiation and one with prior radiotherapy). The fourth patient died of treatment-related toxicity. The 3 year survival for all 42 eligible patients was 90%. Dose reduction and treatment postponement were necessary in 25 and 14 patients respectively. Ten patients experienced granulocytic fever. Previously irradiated patients tolerated chemotherapy as well as non-irradiated patients. Immediately after HOP chemotherapy a mass persisted in 16 of 17 patients with retroperitoneal masses of > or = 100 mm at presentation. Three of these residual lesions were resected within the following 6 months showing complete necrosis. Four lesions dissolved spontaneously during the first year of follow-up. Nine lesions persisted for > or = 1 year (one after consolidation radiotherapy) without leading to relapse. Four of seven patients with mediastinal lesions achieved CR and three a PR after HOP chemotherapy. The HOP chemotherapy regimen is highly effective in patients with advanced metastatic seminoma or those relapsing after previous radiotherapy, but is associated with a high risk of toxicity, in particular myelotoxicity. PMID- 7880749 TI - Whole bladder wall photodynamic therapy for refractory carcinoma in situ of the bladder. AB - Whole bladder wall photodynamic therapy (PDT) with haematoporphyrin derivative and an argon dye laser as a light source was performed on 34 patients with refractory carcinoma in situ (CIS) of the bladder. Twenty-five of the 34 patients (73.5%) had achieved a complete response (CR) at 3 months after the treatment. The median follow-up for these CR patients is 49.3 months. Although recurrence within 2 years of follow-up occurred in 14 (77.8%) of the 18 CR patients followed to that point, since most of the recurrent tumours were superficial and low-grade papillary tumours, transurethral resection of the bladder tumours appeared to be sufficient. Of the total of 34 patients, ten were alive with bladder intact with a mean follow-up period of 64.0 months. Skin photosensitivity and transient decrease in bladder capacity were noted as adverse reactions, caused by retention of haematoporphyrin derivative in the skin and normal portion of the bladder. These data suggest that PDT can be an effective form of therapy for CIS of the bladder. PMID- 7880750 TI - Why are a quarter of all cancer deaths in south-east England registered by death certificate only? Factors related to death certificate only registrations in the Thames Cancer Registry between 1987 and 1989. AB - This paper describes the results of a study set up to investigate factors associated with the high proportions of 'death certificate only' registrations (DCOs) for all cancers registered in south-east England between 1987 and 1989 and to identify those which might be subject to registry intervention. DCOs as a proportion of all registrations (n = 162,131) were analysed by age, sex, district of residence, place of death and survival. DCO registration ratios (standardised for age and sex) were then derived for each of the 56 districts in the Thames Regions. A multiple logistic regression model was generated to estimate the effect of age at diagnosis, tumour survival and patient sex on final source of registration. To minimise the number of dummy variables needed, each of the 56 districts was ranked into quartiles: quartile 1 contained the 14 districts with the lowest age- and sex-standardised ratios for DCO registrations and quartile 4 comprised the 14 districts with the highest DCO ratios. Final source of registration was treated as a binomial trial (case notes or death certificates). The significance of associations was measured using the deviance difference as an approximate chi-square statistic. The effect of each variable on source of registration was estimated as an odds ratio. Interaction terms were also fitted. To estimate the effect of place of death on DCO registrations, a second model was generated for deceased patients only (n = 98,455, adding 'place of death' to the list of explanatory variables already used. A further interaction term was fitted to account for interaction between place of death and district quartile of residence. Around 24% of all patient deaths were registered as DCOs by the Thames Cancer Registry between 1987 and 1989. Of these, 40.9% died in an acute NHS hospital setting, 37.1% died at home, 10.4% died in hospices and 3.4% died in non NHS hospitals. Increasing age, decreasing survival, district of residence and place of death were positively associated with death certificate registrations. The district effect was sustained in the regression model with significant positive associations shown for DHA quartile of residence. In the deceased group of patients, both district of residence and place of death were independent predictors of DCOs. Death occurring outside the acute NHS hospital setting increased the odds of being a DCO within and across district quartiles. DCOs could be reduced by better case ascertainment in some districts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7880751 TI - Ovarian cancer, ovulation and side of origin. AB - Reports of more right-sided ovarian cancers and more ovulations in the right ovary seemed to offer powerful support for the theory that ovulation, per se, leads to ovarian cancer risk. We examined laterality in 25,692 epithelial ovarian cancers diagnosed in 1973-89 included in the US Surveillance, Epidemiology, and End Results system of cancer registries. Ovarian cancer occurred equally often in the left and right ovaries in this large series of incident cases. PMID- 7880752 TI - Risk factors for benign ovarian teratomas. AB - Risk factors for benign ovarian teratomas have been analysed in a case-control study conducted in Milan. Cases were women aged less than 65 years with a histologically confirmed diagnosis of benign ovarian teratoma who were admitted to a network of Obstetrics and Gynecology Departments in Milan. A total of 77 women aged 16-64 years were interviewed. Controls were women admitted to hospital for acute, non-gynaecological, non-hormonal and non-neoplastic diseases; 231 controls were interviewed (age range 15-64 years). Cases tended to be more educated: in comparison with women with less than 7 years of education, the estimated relative risk (RR) of ovarian benign teratoma was 1.6 and 2.5 respectively in women with 7-11 and 12 or more years of schooling, the trend in risk being statistically significant (chi 2(1) trend 5.39, P < 0.01). Four of the 77 cases (5.2%) and two of the 231 controls (0.9%) reported a history of infertility, with a corresponding RR of 8.3 (95% confidence interval 1.3-54.0). There was no clear relation between parity and risk of ovarian benign teratomas: in comparison with nulliparae, the estimated RRs were 1.1 and 0.7 respectively in women reporting one or two or more births (chi 2(1) trend 0.53, P = not significant). No relation emerged between marital status, age at menarche, menstrual cycle pattern, menopausal status, abortions, age at first pregnancy, oral contraceptive use and risk of ovarian benign teratomas. PMID- 7880753 TI - Reproductive and menstrual factors in relation to mammographic parenchymal patterns among perimenopausal women. AB - The relationship between mammographic patterns and reproductive and menstrual factors was examined in 3640 Norwegian women, aged 40-56 years, participating in the Third Tromso study conducted in 1986-87. Epidemiological data were obtained from questionnaires. The mammograms were categorised into five groups. This categorisation is based on anatomic-mammographic correlations, following three dimensional (thick slice technique) histopathologic-mammographic comparisons, rather than simple pattern reading. Patterns 1-3 were combined into a low-risk group and patterns 4 and 5 into a high-risk group for analysis. Women who had more than four children were 90% less likely to have a high-risk pattern than nulliparous women (OR = 0.09, 95% CI 0.04-0.16) controlling for age, weight, height and menopausal status. Furthermore, those who first gave birth over 34 years of age were more than twice as likely to have a high-risk pattern than those giving birth in their teens (OR = 2.37, 95% CI 1.23-4.56) adjusting for parity. Among post-menopausal women, age at menarche was negatively (P for trend = 0.015) and late age at menopause positively (P for trend = 0.072) related to high-risk patterns. Among premenopausal women, age at menarche was positively related to high-risk patterns (P for trend = 0.001). Also, menopausal status rather than age was associated with high-risk patterns. These findings support the opinion that reproductive and menstrual factors are involved in determining the mammographic parenchymal pattern among perimenopausal women. PMID- 7880754 TI - Leukaemia mortality around French nuclear sites. AB - This study was designed to investigate leukaemia mortality in the population under the age of 25 residing around the 13 French nuclear sites operating in 1985. In four geographical zones defined according to the distance from the site, 503 exposed communes were identified and followed up between 1968 and 1989. A total of 4,132,000 person-years of observation were accumulated. The number of leukaemia deaths observed (69) did not differ from the expected number (86.15) estimated according to national mortality statistics. There was no difference in the risks of leukaemia mortality according to sex, age, type of installation and no trend with an increasing distance from installations. PMID- 7880755 TI - Depression: lifting the cloud (continuing education credit). PMID- 7880756 TI - Recovery of antioxidants and reduction in lipid hydroperoxides in murine epidermis and dermis after acute ultraviolet radiation exposure. AB - In previous studies we have found that a single acute dose of ultraviolet radiation to murine skin causes a large degree of destruction of enzymic and non enzymic antioxidants immediately after irradiation. In the present study, we wished to elucidate the recovery of antioxidants after a single dose of ultraviolet (UV) radiation. We measured antioxidants and lipid hydroperoxides (as a marker of membrane damage) in murine epidermis and the dermis at 0, 3, 12, 24, 72 and 120 h after exposure to UV radiation (25 J/cm2, UVA+UVB). Lipid hydroperoxides showed the highest values immediately after UV exposure and returned to control values within 24 h in both epidermis and dermis. The activities of catalase, glutathione peroxidase and glutathione reductase showed the lowest activities immediately after UV exposure; superoxide dismutase activities reached a minimum at 3 h postexposure. The pattern of recovery was different for each enzyme and for epidermis and dermis. The activities of superoxide dismutase and catalase decreased remarkably and recovered slowly. Superoxide dismutase in the dermis recovered full activity by 120 h and in the epidermis by 12 h. Catalase activity in both epidermis and dermis had returned to only 50% of control activity at 120 h, although the epidermis showed a temporary increase (to 93%) at 24 h. Glutathione peroxidase and glutathione reductase were slightly decreased immediately after irradiation, recovered to 100% at 3 h and then increased to 200-250% in both the epidermis and the dermis at various times; values had returned to 100% in epidermis by 120 h but remained elevated in dermis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880757 TI - Differences in narrow-band ultraviolet B and broad-spectrum ultraviolet photocarcinogenesis in lightly pigmented hairless mice. AB - The carcinogenic effect of 4 ultraviolet (UV) sources was studied in lightly pigmented hairless mice. Two narrow-band UV sources, Philips TL01 and Philips TL12 with a Tempax filter, and two broad-spectrum UV sources, Philips TL12 and Bellarium S, were used. Exposure doses were calculated from the CIE erythema action spectrum. Four groups of mice (n = 20) were exposed to a nonerythemogenic dose (low dose), and 4 groups were exposed to an erythemogenic dose (high dose) of each of the 4 UV sources. One group (control) was not irradiated. The mice in the 4 low-dose groups were all exposed to 0.6 basic minimal erythema doses (B MED) 5 days/week, and all the mice in the high-dose groups to 1.2 B-MED 5 days/week. After 16 weeks of acclimatization, the doses were doubled. Bellarium S and Philips TL12 were equally carcinogenic in the low-dose regimen and the high dose regimen. Mice exposed to Philips TL12 with a Tempax filter developed tumors significantly earlier compared with Bellarium and Philips TL12. Philips TL01 was more carcinogenic than any of the other UV sources. Equally erythemogenic doses calculated from the CIE erythema action spectrum seem to be more carcinogenic when derived from narrow-band UVB sources than from broad-band UV sources. PMID- 7880758 TI - Contact photosensitivity to nonoxynol used in antiseptic preparations. AB - Nonoxynols are nonionic surface-active agents used as surfactant in numerous cosmetic products and antiseptic preparations. Recently nonoxynol contact allergy has been described. We report two patients who presented a contact photosensitivity to nonoxynol 10 contained in Hexomedine transcutanee. Among 32 control subjects, we found 13 positive photopatch tests to Hexomedine transcutanee and 4 positive photopatch tests to nonoxynol 10. Surprisingly, the authors observed that only undiluted nonoxynol was phototoxic. PMID- 7880759 TI - In vitro phototoxic activities of new quinolone antibacterial agents: lipid peroxidative potentials. AB - To determine the fundamental photochemical properties of new quinolones that can induce photosensitivity, the in vitro phototoxicity of these drugs (enoxacin, norfloxacin, ofloxacin, ciprofloxacin, and lomefloxacin) was examined with respect to photosensitizing ability to peroxidize unsaturated lipid squalene in ethanol solution. Lomefloxacin and ciprofloxacin showed the highest efficiency in sensitization of peroxidation of the lipid. Moderate repression of peroxidation occurred by addition of sodium azide (a quencher of singlet molecular oxygen), suggesting that the nonsinglet oxygen mechanism is operative in addition to the singlet oxygen mechanism. PMID- 7880761 TI - Collagen synthesis in human skin in vivo: modulation by aging, ultraviolet B irradiation and localization. AB - The effect of aging, sex, skin location and a short whole body ultraviolet B (UVB) phototherapy on type I and type III skin collagen synthesis were studied by measuring carboxy- and aminoterminal propeptides of type I and aminoterminal propeptide of type III procollagens (PICP, PINP and PIIINP, respectively) in suction blister fluid (SBF). The concentrations of PICP and PIIINP correlated negatively with age in the material of 30 men and 27 women (age range 23-86 years, mean age 51 years). As the subjects were divided into 3 age groups (23-34, 35-54 and 55-86 years) and the mean concentrations of the procollagens were compared between the groups, the youngest age groups in men and in the whole material had significantly higher concentrations than the two older age groups. These results confirm the previous results, which have shown by other methods that skin collagen synthesis decreases during aging. SBF was also obtained from 4 different body regions (back, arm, abdomen and leg) of 5 young male subjects and from 2 different body regions (abdomen and thigh) of 9 older subjects. Wide individual range in the concentrations of PICP, PINP and PIIINP was noticed but, in general, none of the body regions seemed to have more excessive collagen synthesis than the other ones. SBF was further collected from abdominal skin of 8 young male dermatological patients receiving UVB phototherapy. When the concentrations of PICP and PIIINP in SBF obtained before the treatment, after the treatment and from the covered control area were compared no statistical differences were noted, suggesting that short UVB treatment has no effect on skin collagen synthesis in vivo. PMID- 7880760 TI - In vivo evidence that ultraviolet B-induced suppression of allergic contact sensitivity is associated with functional inactivation of Th1 cells. AB - Having previously shown in vitro that ultraviolet B (UVB)-treated Langerhans cells (LC) can induce antigen-specific proliferative unresponsiveness and tolerance in Th1 (but not Th2) cells, we wanted to determine whether cutaneous exposure to UVB radiation prior to hapten-painting would produce similar differential effects in hapten-reactive Th1 and Th2 T cells in vivo. C3H/HeN mice were exposed to UVB (200 J/m2/day) through abdominal skin on days -4 through -1, followed by painting dinitrofluorobenzene (DNFB) on the irradiated skin on days 1 and 0. Induction of allergic contact sensitivity (CS) was assayed by ear swelling responses to DNFB and by the proliferative responses of draining lymph node cells (LNC) to DNBS. UVB-irradiated and hapten-painted mice (in comparison to a control panel of unirradiated and DNFB-painted mice) displayed suppressed ear swelling responses to DNFB and suppressed LNC proliferation to DNBS. However, LNC from either panel of mice proliferated well in response to exogenous interleukin 2 (IL-2). To examine effects on Th1 and Th2 cells, lymphokines were assayed from supernatants of DNBS-stimulated LNC. The Th1-associated lymphokines, interferon-gamma and IL-2, were the predominant cytokines detected in samples taken from unirradiated and DNFB-painted mice. Both of these cytokines were reduced markedly in samples from UVB-treated and DNFB-painted mice. Except for miniscule amounts of IL-10, no Th2-associated lymphokines were detected in LNC supernatants from either panel of mice. These results suggest that UVB-induced suppression of CS in vivo is associated with functional inactivation of hapten reactive Th1 cells. PMID- 7880762 TI - Treatment of psoriasis with psoralens and ultraviolet A. A double-blind comparison of 8-methoxypsoralen and 5-methoxypsoralen. AB - Thirty-eight patients with plaque-type psoriasis were enrolled in a double-blind psoralen plus ultraviolet A (PUVA) treatment study comparing the efficacy and side effects of 5-methoxypsoralen (5-MOP) and 8-methoxypsoralen (8-MOP). Patients treated with 8-MOP healed significantly faster than those on 5-MOP for 6 weeks of treatment, but there was no significant difference after 9 weeks. There was no significant difference in side effects between the two groups, but nausea tended to be more common in the 8-MOP group. One patient on 5-MOP had signs of toxic hepatitis. The importance for maximizing absorption of taking 5-MOP with food is stressed, and PUVA treatment should be given 3 h after intake of the drug. PMID- 7880763 TI - Scattered ultraviolet radiation underneath a shade-cloth. AB - Ultraviolet (UV) radiometers and polysulphone film badges were used to study scattered UV radiation from sunlight underneath a shade-cloth of a size about 70 x 100 cm2. The transmittance of erythemal UV radiation through the shade-cloth was found to be 0.14 +/- 0.03. The results of the measurements were used to derive the shade ratio, defined as the ratio of the erythema UV irradiance or dose in the shadow to that outside the shadow. It was found that the shade ratio is not the same as the transmittance. Its value depends on the height and the orientation of the irradiated object. For a horizontal detector, the shade ratio decreases by more than 20% as the detector height increased from 0.37 m to 1.36 m. At a height of 1.36 m, the shade ratio decreased by about 100% as the horizontal meter was rotated to the vertical direction. The value of the shade ratio (0.11) approached the value of the transmittance (0.14) as the height (1.53 m) of the horizontal meter approached the height of the shade-cloth (1.7 m). Polysulphone film badges were attached to 10 sites on 2 identical manikins. One manikin was exposed at the centre of the shadow underneath the shade-cloth and the other was exposed in open area for four orientations in both Durham and Brisbane. The experiments performed in Durham were under an overcast sky and those performed in Brisbane were under a clear sky. The results showed that the shade ratio varied from site to site. The mean ratios of the facial dose in the shadow to that outside the shadow were found to be 0.70 +/- 0.1 and 0.35 +/- 0.10 for Durham and Brisbane measurements respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880764 TI - Mary Glover lecture: 25 years of connecting: a portrait of the Canadian Association of Neuroscience Nurses. PMID- 7880765 TI - Environmental triggers in multiple sclerosis. Fact or fallacy? AB - Multiple Sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. In the early, most common course of the disease there are seemingly random attacks or exacerbations usually followed by partial or complete recovery. It has long been postulated that environmental events such as infection, emotional stress, or trauma play some role in triggering exacerbations, worsening of the disease, or even the onset of MS. Indeed there have been monetary awards by the courts based on possible influence on the disease following motor vehicle accidents. This paper will describe a prospective study undertaken at the UBC MS Clinic evaluating the impact of infection, emotional stress, and physical trauma on the course of the disease in 50 relapsing-remitting patients participating in the Betaseron trial. During the first two years of the clinical trail this cohort kept diaries documenting environmental "events". The participants were evaluated clinically and with Magnetic Resonance Imaging (MRI) every six weeks. The potential triggers or events are correlated with disease activity seen on MRI, relapse occurrence and disease progression according to the neurological exam. The results of the study and their implications for patient counselling will be presented. PMID- 7880766 TI - A comparative study of systemized vs. random tracheostomy weaning. AB - The purpose of this study was to compare a systematic tracheostomy weaning procedure to a random weaning approach by asking the question: "What is the benefit to the patient of a systematic vs. random weaning process for tracheostomy removal as defined by the number of weaning attempts and post weaning complications?" A tracheostomy weaning procedure was developed at St. Boniface General Hospital as a joint venture between the neuroscience nurses and neurosurgeons in response to a perceived clinical need. This project evaluated the systemic procedure in two neuroscience units in Manitoba on ten adult patients who met the assessment criteria for tracheostomy removal established in the procedure. The patients were monitored for thirty days post removal for complications. In addition, a retrospective chart review was completed on twenty charts of patients who had undergone random tracheostomy weaning from 1990-1992. Content analysis of the documentation immediately before, during and after each tracheostomy weaning procedure was undertaken. The results of the study indicate that there were fewer weaning attempts required for the patients with the systemized procedure than the random procedure, and although not statistically significant, there were fewer post-removal complications per patient in the systemized procedure than with the random procedure. Content analysis of the retrospective data indicates that the random tracheostomy weaning procedure was subject to the individual nurses' judgement. The systemized procedure was more standardized and conformed to the protocols in the procedure. Most importantly, the patient's comfort and safety were greatly enhanced through the use of standard tracheostomy weaning procedure. PMID- 7880767 TI - Non-operative management of a common bile duct injury sustained during cholecystectomy in a morbidly obese patient. (Non-operative repair of CBD injury). AB - A 29 year old morbidly obese patient suffered injury to his common bile duct during cholecystectomy. Subsequent access to the biliary tree was obtained by using a long heavy gauge needle after first opacifying the system with contrast injection through a nasobiliary tube. It is now twenty six months after initial percutaneous biliary drainage placement and eighteen months after removal of all biliary access. The patient is asymptomatic and has normal liver function tests. This technique can be useful in morbidly obese patients who are at increased risk from surgical repair of biliary duct injuries. PMID- 7880768 TI - Treatment strategies for hepatic metastases from pancreatic cancer in patients previously treated with radical resection combined with intraoperative radiation therapy. AB - Since 1984, we have performed extended radical resection combined with extended intraoperative radiation therapy (IORT) for pancreatic cancer. This approach has provided a dramatic improvement in long-term survival and control of local recurrence. Hepatic metastases, however, remain an unsolved problem. Among patients with this combined therapy, we found hepatic metastases in 8 of 22 patients postoperatively. Four of these 8 were considered candidates for further therapy and underwent treatment for their hepatic metastases, the other 4 had too extensive disease. Two patients with multiple hepatic metastases underwent percutaneous ethanol injection therapy and chemotherapy, but they died within a year. Two patients with a solitary hepatic metastases underwent hepatic resection. One patient died two years and six months after the first operation because of multiple metastases in the liver and both lungs, while the other patient is still alive over six years after the first operation with an excellent performance status. When a patient has no local recurrence and a solitary metastasis in the liver, surgical resection of the liver metastasis should be performed. PMID- 7880769 TI - HPB surgery: an independent speciality or a branch of digestive surgery? PMID- 7880771 TI - Bleeding pseudocyst of the pancreatic head. The role of omentoplasty and local hemostasis. AB - Treatment of bleeding psedoaneurysms and pseudocysts of the pancreas is controversial. Surgical treatment with pancreatic resection or trancystic arterial ligation is not always satisfactory since postoperative mortality rate is high, especially for lesions located in the pancreatic head and rebleeding is not unusual. Two patients with bleeding pseudoaneurysms (one post traumatic, one spontaneous) and one with a hemorrhagic pseudocyst of the pancreatic head were treated surgically with arterial suture and omentoplasty. Bleeding was controlled in all, without any postoperative mortality or morbidity. No rebleeding occurred with a follow up of 33, 26 and 12 months. Trancystic ligation of bleeding vessels with omentoplasty may be a useful approach, which should be compared to arterial embolization in the future. PMID- 7880770 TI - Attitudes towards detection and management of hepatic metastases of colorectal origin: a second look. AB - In the present study we undertook an international postal survey to assess the current attitudes towards the detection and management of hepatic metastases in colorectal cancer patients, who have been operated on with curative intent. Results of this survey were compared to results of an earlier survey, held in 1985. Both surveys indicate that there is no consensus on the follow-up of patients at risk of hepatic metastases. Especially the interpretation of unexplained rises in carcinoembryonic antigen (CEA) levels leads to much controversy. Only 37% of the hospitals performing liver surgery were willing to perform second-look laparotomies based on CEA only. Also there is no agreement on the maximum number of liver metastases that will justify partial liver resection for cure. Clearly, there is a need for prospective randomized trials on which a more rational policy regarding hepatic metastases in colorectal cancer patients can be based. PMID- 7880772 TI - Hepatic angiomyolipoma. AB - Hepatic angiomyolipomas are rare benign tumours. First reported by Ishak in 1976. Since then, the world literature showed only 32 cases including 8 autopsy findings. In this paper a retrospective analysis of the published data will be presented and the first report of the preoperative colour doppler and intraoperative sonography appearances will also be described. PMID- 7880773 TI - An analysis of infectious failures in acute cholangitis. AB - To determine the factors responsible for therapeutic failures in acute cholangitis, a series of 127 patients was analyzed. There were 64 females and 63 males whose mean age was 57.2 years. Ninety-four (74.0%) of these patients were clinically cured with initial measures, whereas 33 patients (26%) failed initial therapy for an infectious reason. No differences were observed between the two groups in regard to age and gender. However, more patients in the group that failed had a malignant cause for their bile duct obstruction (72.7% vs. 42.6%, p < 0.01) and had a pretreatment positive blood culture (45.5% vs. 13.8%, p < 0.01). Patients who failed had a higher mean total bilirubin level (9.7 mg/dl vs. 5.5 mg/dl, p < 0.005) and more of them had a level greater than 2.2 mg/dl (97% vs. 69.9%, p < 0.001). Also, more bile cultures were initially positive (93.9% vs. 76.6%, p < 0.05) and more organisms were isolated per culture (3.88 vs. 2.86, p < 0.03) in the patients who failed. In addition, more patients failed who had two or more organisms in the bile (33% vs. 8.3%, p < 0.02). Patients in whom Candida, or any panresistant organism was isolated also tended to fail. Multivariant analysis showed that malignancy, bacteremia, bilirubin > or = 2.2 mg/dl, > or = 2 organisms in the bile and a panresistant organism were the best predictors of treatment failure with a serum bilirubin level > or = 2.2 mg/dl being the variable that increases a patient's log-odds ratio of failure the greatest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880774 TI - Liver transplantation with incidental gallbladder carcinoma in the recipient hepatectomy. AB - Gallbladder carcinoma (GBCA) is the most common malignancy of the biliary tract and is often found seredipitiously after cholecystectomy. We report the first two cases of incidental GBCA in the native gallbladder of two liver transplant recipients. Both patients are 2.5 years following uneventful orthotopiic liver transplantation (OLTx) with no evidence of recurrent disease. Pathology of both recipients was early and favorable. Neither patient received any further therapy. Given the incidence of GBCA and the evolution of OLTx we would anticipate this finding to be more prevalent. PMID- 7880775 TI - Does prophylactic endoscopic sclerotherapy prevent variceal bleeding or not? A question of experimental design. PMID- 7880776 TI - Diagnosis and surgical treatment of hepatic hydatid disease. AB - In this report, 226 patients with hydatid disease admitted to the Surgical Department of Erciyes University (Kayseri) and Sisli Etfal Hospital (Istanbul) in Turkey between 1978 and 1990 were reviewed retrospectively. 102 patients (45.1%) were male and 124 (54.9%) female. The most frequent symptom was right upper abdominal pain (66%). The most frequent signs were hepatomegaly (43.8%) and palpable mass (39%). 167 patients (73.9%) were examined with ultrasonography which has a diagnostic value of 94%. Preoperative complications were infection of cyst (7%), intrabiliary rupture (3.5%) and anaphylactic shock (0.4%). Patients were operated on by various techniques; omentoplasty (101), external drainage of residual cavity (64), marsupialization (25), capitonnage (15), introflexion (10), pericystectomy (6), and hepatic resection (5). Main postoperative complications were wound infection (12%) and biliary fistula (2.6%). Total mortality rate was 1.8% in this series. PMID- 7880777 TI - Splanchnic haemodynamics and vasoactive agents in experimental cirrhosis. AB - It is well known that portal hypertension is associated with a hyperdynamic systemic circulatory state. This study measures systemic and splanchnic haemodynamics in an experimental rat model of hepatic cirrhosis. It also investigates the association between haemodynamic changes in cirrhotic animals and circulating levels of the vasoactive hormones glucagon and vasoactive intestinal polypeptide (VIP). Splanchnic blood flow was significantly increased in the cirrhotic group (13.2 +/- 1.3 vs. 9.2 +/- 1.6 ml/min, P < 0.05). Circulating levels of glucagon and VIP were two and five fold increased respectively in cirrhotic animals compared to controls. There was a strong correlation between portal pressure and glucagon levels in the cirrhotic group (r = 0.85). Raised splanchnic blood flow is partly responsible for elevated portal pressure in this model and this rise may be humorally mediated. PMID- 7880778 TI - Percutaneous alcohol sclerotherapy of simple hepatic cysts. Results from a multicentre survey in Italy. AB - The increased use of Ultrasonography (US) has led to increased detection of simple hepatic cysts. For symptomatic cysts treatment is necessary. Until some years ago surgery was the only therapy. We have treated a large number of patients with Percutaneous Alcohol Sclerotherapy (PAS) and evaluated retrospectively the efficacy of this approach. Data on 21 patients with symptomatic simple hepatic cysts were reviewed retrospectively. Cysts had a mean diameter of 9 cm (range: 7-15 cm). PAS was always performed under local anesthesia and US guidance. 25% of the volume was replaced with 95% ethanol and then completely aspirated after 20-30 minutes. No complications or deaths occurred. In all patients symptoms disappeared after treatment. In 15 out of 21 cases there was no evidence of residual cyst on US, computed tomography (CT) or magnetic resonance (MRI). In 6 patients with shorter follow-up, cysts showed a mean reduction in diameter of 50%. The mean follow-up was 18 months (range 6-60 months). We conclude that PAS is easy with low risk for the patients and with good long-term results; it should therefore become the procedure of choice for simple hepatic cysts. PMID- 7880779 TI - Portal hypertension promotes bacterial translocation in rats mono- and non mono associated with Escherichia coli C25. AB - The basis for the high incidence of infectious complications in portal hypertension (PHT) remains unclear. The hypothesis that PHT induces bacterial translocation (BT) was tested in a rat model with or without mono-association with streptomycin resistant Escherichia coli C25 and with or without hypovolemic shock. PHT was achieved by partial portal vein ligation and three weeks later hypovolemic shock (HS) was induced. Blood, liver, spleen and mesenteric lymph nodes cultures were performed twenty-four hours later. PHT promoted BT to mesenteric lymph nodes in indigenous flora (4/6 [67%]) and mono-associated animals (7/9 [78%]) compared to sham laparotomy and sham shock (SL + SS) animals (0/6 [0%] and 2/9 [22%] respectively) (p = 0.03). The combination of PHT and HS resulted in increased mortality in mono-associated (7/15 [47%]) and non mono associated animals (8/15 [53%]). No significant translocation was noted in liver and spleen and bacteremia was found only in the PHT + HS mono-associated animals (4/8 [50%]). PHT induces BT to mesenteric lymph nodes and this may account for the high incidence of septic complications associated with PHT. In this model, the addition of HS to PHT leads to an increased mortality but without uniform translocation of the gut flora beyond mesenteric lymph nodes. PMID- 7880780 TI - Prospective multicentre study of the accuracy of surgery for horizontal strabismus. AB - Eight centres throughout the United Kingdom cooperated with a prospective evaluation of the accuracy of surgery for horizontal strabismus. The eight centres were divided into four with a specialist interest in strabismus and four offering a general ophthalmic service. Each participating surgeon was asked to indicate the anticipated outcome of surgery and, thereafter, orthoptic examinations were made post-operatively to determine the actual outcome. Two hundred and five cases were included in the study and it is hoped the results will serve as useful guidelines for those departments wishing to undertake audit of their own strabismus surgery. There was no statistically significant difference in the accuracy of surgical alignment achieved by strabismus specialists and general ophthalmologists. PMID- 7880781 TI - Acute angle closure glaucoma: relative failure of YAG iridotomy. PMID- 7880782 TI - Latanoprost administered once daily caused a maintained reduction of intraocular pressure in glaucoma patients treated concomitantly with timolol. AB - The long term effects of two dose regimens of latanoprost (PhXA41) administered to eyes concomitantly treated with timolol which had not adequately been controlled by timolol alone were compared. A total of 50 patients, 17 with primary open angle glaucoma and 33 with capsular glaucoma, were recruited from five clinics. All had glaucomatous visual field defects and an intraocular pressure (IOP) of at least 22 mm Hg despite treatment with 0.5% timolol twice daily. Patients were randomised to two treatment groups. In one group 0.006% latanoprost was given twice daily, in the other group placebo was given at 8 am and latanoprost at 8 pm for 3 months, with concomitant timolol treatment in both groups. Average daytime IOP (mean (SD)) at baseline (on timolol alone) and after 4 and 12 weeks' treatment was 24.8 (3.6), 16.8 (4.3), and 15.7 (2.4) mm Hg respectively with once daily application of latanoprost and 24.9 (2.9), 18.1 (3.0), and 18.0 (3.6) mm Hg respectively with latanoprost twice daily. No clinically significant side effects were observed during treatment. Latanoprost causes a marked and sustained IOP reduction in eyes which are also being treated with timolol. Latanoprost given once daily is at least as effective and probably superior to a twice daily dose regimen. PMID- 7880783 TI - Influence of age, systemic blood pressure, smoking, and blood viscosity on orbital blood velocities. AB - The influence of multiple systemic factors upon the blood velocities obtained from the orbital circulations was investigated. The velocities obtained by colour Doppler imaging from the ophthalmic artery, central retinal artery, and vein from 95 ophthalmologically healthy volunteers were analyzed. The effects of age, systemic blood pressure, and smoking habit were examined. In 24 volunteers blood viscosity was also measured and its relation with blood velocity assessed. Age was weakly negatively correlated with the blood velocities in the ophthalmic artery and weakly positively correlated with resistance to flow in the retinal circulation. Systolic blood pressure showed a positive correlation with the peak systolic velocities in the arteries while cigarette smoking was associated with lower ophthalmic artery velocities. Increased haematocrit and viscosity were positively correlated with resistance to flow proximal to the ophthalmic artery and red cell rigidity negatively correlated with the pulsatility of flow in the retinal vein. These results help to identify the roles of systemic conditions in the ocular circulation. The influence of blood viscosity on retinal venous flow may be relevant to the pathogenetic mechanisms of conditions such as central retinal vein occlusion. PMID- 7880784 TI - Corneal transplantation and infectious hepatitis. PMID- 7880786 TI - Extensive intrafamilial and interfamilial phenotypic variation among patients with autosomal dominant retinal dystrophy and mutations in the human RDS/peripherin gene. AB - Clinical phenotypes of patients with mutations in the human RDS/peripherin gene are described. A 67-year-old woman, who carried a 1 base pair deletion in codon 307, presented with typical late onset autosomal dominant retinitis pigmentosa (RP). In another autosomal dominant pedigree, a nonsense mutation at codon 46 caused 'inverse' retinitis pigmentosa-like fundus changes associated with progressive cone-rod degeneration in a 58-year-old man, whereas his 40-year-old son presented with yellow deposits in the retinal pigment epithelial layer resembling a pattern dystrophy, and with moderately reduced rod and cone function, as determined by two colour dark adapted threshold perimetry and electroretinography. It is suggested that both clinical pictures within this latter family may represent manifestations of fundus flavimaculatus. The clinical data of the three patients provide further evidence for the remarkable variety of disease expression within and between families with mutations in the RDS/peripherin gene. Currently, the most comprehensive statement could be that RDS/peripherin mutations are associated either with typical RP or with various forms of flecked retinal disease. PMID- 7880785 TI - Autosomal dominant retinitis pigmentosa mapping to chromosome 7p exhibits variable expression. AB - The genetic locus causing autosomal dominant retinitis pigmentosa (adRP) has recently been mapped in a large English family to chromosome 7p. Eight affected members of this family were studied electrophysiologically and psychophysically with dark adapted static threshold perimetry and dark adaptometry. The phenotypes observed fell into three categories: minimally affected with no symptoms, and normal (or near normal) electrophysiology and psychophysics; moderately affected with mild symptoms, abnormal electroretinograms, and equal loss of rod and cone function in affected areas of the retina; and severely affected with extinguished electroretinograms and barely detectable dark adapted static threshold sensitivities. The mutation in the gene on 7p causing adRP in this family causes regional retinal dysfunction with greatly variable expressivity ranging from normal to profoundly abnormal in a manner not explained by age. PMID- 7880787 TI - Accuracy in strabismus surgery. PMID- 7880788 TI - Latanoprost--a promising new glaucoma drug. PMID- 7880789 TI - Comparison of colour discrimination and electroretinography in evaluation of visual pathway dysfunction in aretinopathic IDDM patients. AB - The slow progression of diabetic retinopathy makes it difficult to assess the effects of intervention therapy. There is thus a need for surrogate markers of visual change in diabetes. Colour vision tests and electroretinography (ERG) may be useful in this regard; yet little is known of their relative performance in the assessment of visual dysfunction in diabetes. The aim of the present study was to compare colour discrimination (100 hue test) and ERG indices (oscillatory potentials (OP) and pattern ERG (PERG)) in the evaluation of aretinopathic IDDM patients. Colour discrimination was abnormal in 10 aretinopathic IDDM patients when compared with nine age matched controls; mean square root 100 hue error scores were 10.38 (SD 2.89) versus 4.77 (1.87) respectively, p < 0.01. OP implicit times of the ERG were also abnormal; for example, for right eye, mean OP1 implicit time for diabetics versus OP1 implicit time for controls was 20.1 (2.0) versus 18.6 (1.4) ms, p = 0.03. Comparison of the two techniques suggested that the 100 hue test was more sensitive and more specific than ERG OP implicit times in the detection of diabetic visual dysfunction in these patients. PMID- 7880790 TI - One of the earliest ophthalmologists. PMID- 7880791 TI - Placebo controlled trial of fusidic acid gel and oxytetracycline for recurrent blepharitis and rosacea. AB - A prospective, randomised, double blind, partial crossover, placebo controlled trial has been conducted to compare the performance of topical fusidic acid gel (Fucithalmic) and oral oxytetracycline as treatment for symptomatic chronic blepharitis. Treatment success was judged both by a reduction in symptoms and clinical examination before and after therapy. Seventy five per cent of patients with blepharitis and associated rosacea were symptomatically improved by fusidic acid gel and 50% by oxytetracycline, but fewer (35%) appeared to benefit from the combination. Patients with chronic blepharitis of other aetiologies did not respond to fusidic acid gel but 25% did benefit from oxytetracycline and 30% from the combination. Our results demonstrate the need to investigate patients with blepharitis for concomitant rosacea as they respond well to targeted therapy. PMID- 7880792 TI - Intraocular pressure after peribulbar anaesthesia: is the Honan balloon necessary? AB - Peribulbar anaesthetic blocks were administered to 70 patients and the intraocular pressure (IOP) measured immediately before and within 1 minute of the injections. In 10 patients IOPs were recorded at 1 minute intervals for 15 minutes after injection and then compared with the IOPs recorded in 60 patients after 5 or 10 minutes of Honan balloon ocular compression. The IOP rose significantly after injection in all patient groups and in some cases this increase was marked (over 50 mm Hg in 10 patients). The IOP showed an equivalent drop after 5 or 10 minutes of ocular compression when compared with eyes that did not receive ocular compression. The Honan balloon does not appear to be necessary to reduce IOP in the 10 minutes following peribulbar injection. Furthermore, the occurrence of IOP peaks after peribulbar anaesthesia suggests that the balloon should be used with caution in eyes in which the ocular circulation may be compromised. PMID- 7880793 TI - What future for academic ophthalmology? PMID- 7880795 TI - Adverse ocular effects associated with niacin therapy. AB - In a retrospective survey of patients taking medication for hyperlipidaemia, those taking niacin (nicotinic acid) were more likely (p < 0.05) to report sicca syndromes, blurred vision, eyelid oedema, and macular oedema compared with those who never took niacin. Additionally, 7% of those taking niacin discontinued the drug owing to adverse ocular side effects, while none of the other lipid lowering agents were found to cause these side effects (p = 0.016). Data from spontaneous reporting systems support a possible association of decreased vision, cystoid macular oedema, sicca-like symptoms, discoloration of the eyelids with or without periorbital or eyelid oedema, proptosis, loss of eyebrow or eyelashes, and superficial punctate keratitis with the use of niacin in high doses. Decreased vision may be marked, and if the drug is not discontinued, may progress to cystoid macular oedema. All ocular side effects listed above are reversible if the association with niacin is recognised and the drug is discontinued; both the incidence and severity of the ocular side effects seem to be dose dependent. PMID- 7880794 TI - Herpetic eye attacks: variability of circannual rhythms. AB - BACKGROUND: The issue of seasonal variation of herpetic ocular infections is still controversial. This study was designed to examine whether this variation exists and can be defined as a significant circannual rhythm. METHODS: The patterns of recurrent attacks were monitored in 541 patients over a period of 15 years. Rhythm parameters were analysed according to age, sex, and clinical signs. RESULTS: The majority of herpetic eye attacks exhibited the highest peak in January (p < 0.04), except in the group of atopic children where the incidence of the disease peaked in September (p < 0.05). Among the various clinical forms, significant circannual periodicities were found only in the occurrence of epithelial herpetic keratitis (p < 0.03). The rhythms were detected among males (p < 0.03) but not among females. No direct correlation was demonstrated between the presence of the rhythms and the triggering effect of upper respiratory tract infections. CONCLUSIONS: Chronoepidemiological evaluation of individual reactivation patterns may be beneficial to certain patients and contribute to the optimisation of the treatment when prophylaxis is considered. PMID- 7880796 TI - Assessment of the infectivity of corneal buttons taken from hepatitis B surface antigen seropositive donors. AB - Sixty one corneas taken from 33 hepatitis B surface antigen (HBsAg) seropositive donors and 20 control corneas taken from 12 HBsAg seronegative donors were tested for the presence of HBsAg using reversed passive haemagglutination (RPHA) and enzyme linked immunosorbent assay (ELISA) and for the presence of hepatitis B virus core DNA (HBVcDNA) using the hybridisation technique in their epithelium, stroma endothelium, and storage media. HBsAg was detected by ELISA in the epithelium of one cornea (1.6%), in the stroma endothelial suspensions of six corneas (9.8%), and in the storage media of five corneas (8.2%). HBVcDNA was detected for the first time in the cornea; in the epithelium of four corneas (6.6%), stroma endothelium of nine corneas (14.8%), and the storage media of five corneas (8.2%). The control corneas were negative for HBsAg, while HBVcDNA was detected in the stroma endothelium of two corneas (10%) and in the media of two corneas (10%). This study confirmed that HBV can be present in the human cornea. Preservation in corneal storage media for up to 6 days could not eliminate the virus from the cornea. The possibility of HBV transmission through corneal transplantation should not be overlooked. PMID- 7880797 TI - Pilot study on the effect of topical adrenergic medications on human Tenon's capsule fibroblasts in tissue culture. AB - Recent publications have suggested that the long term use of topical antiglaucoma medications may be detrimental to the outcome of trabeculectomy. In order to investigate this further, the effect of several adrenergic agents and a preservative on the proliferation and viability of human Tenon's capsule fibroblasts in tissue culture were examined. The following compounds were tested: adrenaline (Eppy 1% and pure adrenaline base 1%, Smith & Nephew Pharmaceuticals Ltd); dipivefrine hydrochloride (Propine 0.1% and pure dipivefrine hydrochloride 0.1% Allergan Ltd and Allergan Pharmaceuticals (Ireland) Ltd); benzalkonium chloride (pure benzalkonium chloride 0.01%, Sigma Chemical Company Ltd); the two adrenaline based preparations were also tested in the presence of an antioxidant. None of the tested compounds stimulated the proliferation of fibroblasts. The commercial products tested, their pure compounds, and the preservative all inhibited proliferation and had toxic effects on the cells. In the presence of antioxidant, commercial Eppy and pure adrenaline base appeared to have less effect on proliferation and toxicity. These findings are discussed with reference to the outcome of trabeculectomy. PMID- 7880798 TI - Clinical pathology and retinal vascular structure in the Bardet-Biedl syndrome. AB - A comparative study of clinical pathology and retinal vascular structure is described as studied by vascular casting in an eye of a patient with the Bardet Biedl syndrome. At the time of examination the eye had been almost blind for at least 4 years. The histopathological examination showed a largely uniform loss of the outer retinal layers. The gross pathological examination of the cast ocular fundus showed three distinct zones, an inner zone inside the temporal vascular arcades where retinal vessels had been cast, a mid peripheral zone with bone spicules, and a peripheral zone with neither cast vessels nor bone spicules. The findings are discussed in relation to possible pathophysiological mechanisms involved in the development of retinal dystrophy in the Bardet-Biedl syndrome. PMID- 7880800 TI - Acquired Brown's syndrome and primary Sjogren's syndrome. PMID- 7880799 TI - Experimental approaches to specific immunotherapies in autoimmune disease: future treatment of endogenous posterior uveitis? PMID- 7880801 TI - Langerhans' cell histiocytosis of the eyelid. PMID- 7880802 TI - Atypical mycobacterial wound infection after blepharoplasty. PMID- 7880803 TI - Vogt-Koyanagi-Harada disease during pregnancy. PMID- 7880804 TI - Fatal bilateral necrotising fasciitis of the eyelids. PMID- 7880805 TI - 'Lost' contact lens presenting as an intraocular foreign body. PMID- 7880806 TI - Crystalline keratopathy from Dieffenbachia plant sap. PMID- 7880807 TI - Long-range, small magnitude nonadditivity of mutational effects in proteins. PMID- 7880808 TI - A native tertiary interaction stabilizes the A state of cytochrome c. AB - Certain kinetic intermediates in protein folding are similar to the molten globule, or A state, an equilibrium state of many proteins that is populated under high salt and low pH conditions. Many A states are nearly as compact as native proteins and have native-like secondary structure, but the extent to which nonlocal interactions stabilize the A state is unclear. In this study, thermal denaturation, monitored by circular dichroism, was used to determine the free energy of denaturation of the A state (delta GA<-->D) for Saccharomyces cerevisiae iso-1-ferricytochrome c. Specifically, we examined the wild-type protein, seven variants with amino acid substitutions at the interface between the N- and C-terminal helices, and two variants with mutations at a position close to, but not involved in, the interface. A plot of delta GA<-->D versus delta GN<-->D (the free energy of denaturation of the native state) has a slope near unity, showing that the evolutionarily conserved helix-helix interaction stabilizes the A state to the same degree that it stabilizes the native state. PMID- 7880809 TI - Structures of aromatic inhibitors of influenza virus neuraminidase. AB - Neuraminidase (NA), a surface glycoprotein of influenza virus, is a potential target for design of antiinfluenza agents. The crystal structure of influenza virus neuraminidase showed that in the active site 11 residues are universally conserved among all strains known so far. Several potent inhibitors based on the carbohydrate compound 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid (DANA) have been shown to bind to the conserved active site and to reduce virus infection in animals when administered by nasal spray. Inhibitors of this type are, however, rapidly excreted from physiological systems and may not be effective in order to provide long-time protection. A new class of specific NA inhibitors, which are benzoic acid derivatives, has been designed on the basis of the three-dimensional structure of the NA-DANA complex and modeling of derivatives of 4 (acetylamino)benzoic acid in the NA active site. Intermediates were synthesized and were shown to moderately inhibit the NA activity and to bind to the NA active site as predicted. These rudimentary inhibitors, 4-(acetylamino)-3-hydroxy-5 nitrobenzoic acid, 4-(acetylamino)-3-hydroxy-5-aminobenzoic acid, and 4 (acetylamino)-3-aminobenzoic acid, and their X-ray structures in complexes with N2 (A/Tokyo/3/67) and B/Lee/40 neuraminidases have been analyzed. The coordinates of such inhibitors complexed with NA were used as the starting model for further design of more potent benzoic acid inhibitors. Because the active site residues of NA are invariant, the designed aromatic inhibitors have the potential to become an antiviral drug against all strains of influenza virus. PMID- 7880810 TI - Structural characterization of a (+)-trans-anti-benzo[a]pyrene-DNA adduct using NMR, restrained energy minimization, and molecular dynamics. AB - The (+)-trans-anti-benzo[a]pyrene adduct formed at the N2 amino group of guanine is the major adduct found after metabolic activation of the ubiquitous carcinogen benzo[a]pyrene. The carcinogenic and mutagenic properties of the (+)-trans-anti BP adduct, as well as related adducts, have been extensively studied. A DNA duplex containing a (+)-trans-anti-benzo[a]pyrene adduct covalently attached to the G8 nucleotide in the sequence d(CCTATGT[BP-G]CAC).d(GTGCACATAGG) was synthesized and the structure characterized by one- and two-dimensional NMR spectroscopy, in conjunction with energy minimization and molecular dynamics. This BP-11-mer duplex exhibits NOESY cross-peaks between benzo[a]pyrene protons and BP-G8, C9, A16, and C17 nucleotide protons that clearly delineate the location of the BP moiety in the minor groove of a B-type duplex with the pyrene ring oriented toward the 5' end of the modified strand. Large upfield shifts of A16 and C17 sugar resonances in the partner strand show that the pyrene moiety is situated near these sugars. Analysis of the spectra was complicated by the presence of chemical exchange line broadening of protons located near the (...T[BP-G]C...).(...GCA...) adduct site which shows the presence of a minor conformation for this BP-modified duplex in which TA is the 5' neighboring base pair. Distance restraints determined from NOESY spectra recorded at 20 degrees C were used in restrained and unrestrained energy minimization and molecular dynamics simulations to obtain a structure characteristic of the predominant conformation of the BP-11-mer duplex. The important structural features of the BP 11-mer are similar to those reported by Cosman et al. [(1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1914-1918] for a (+)-trans-anti-BP adduct at a (...C[BP G]C...).(...GCG...) sequence in which CG is the 5' neighboring base pair. No evidence of a conformational equilibrium was reported in this duplex, from which we conclude that the presence of a 5' TA base pair plays a role in the conformational equilibrium. Watson-Crick base pairing is retained in the predominant conformer of the (+)-trans-anti-BP modified duplex, which provides a visualization of a structure that could allow faithful replication. The exchange rate could not be slowed sufficiently to allow individual distance parameters to be obtained for the minor conformer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7880811 TI - Protein backbone dynamics revealed by quasi spectral density function analysis of amide N-15 nuclei. AB - Spectral density functions J(0), J(omega N), and J(omega H + omega N) of individual amide N-15 nuclei in proteins were approximated by a quasi spectral density function (QSDF). Using this function, the backbone dynamics were analyzed for seven protein systems on which data have been published. We defined J(0; omega N) as the difference between the J(0) and the J(omega N) values, which describes motions slower than 50 (or 60) MHz, and J(omega N; omega H+N) as the difference between the J(omega N) and the J(omega H + omega N) values, which describes motions slower than 450 (or 540) MHz. The QSDF analysis can easily extract the J(0; omega N) of protein backbones, which have often some relation to biologically relevant reactions. Flexible N-terminal regions in eglin c and glucose permease IIA and a loop region in eglin c showed smaller values of both the J(0; omega N) and the J(omega N; omega H+N) as compared with the other regions, indicating increases in motions faster than nanosecond. The values of the J(0; omega N) for the backbone of the FK506 binding protein showed a large variation in the apoprotein but fell in a very narrow range after the binding of FK506. Characteristic increase or decrease in the values of J(0) and J(omega N) was observed in two or three residues located between secondary structures. PMID- 7880812 TI - Mechanism of adenylate kinase. The "essential lysine" helps to orient the phosphates and the active site residues to proper conformations. AB - Although how Lys21 interacts with the substrate MgATP of muscle adenylate kinase (AK) can now be deduced from the crystal structure of Escherichia coli AK.MgAP5A [P1,P5-bis(5'-adenosyl) pentaphosphate] [Muller, C. W., & Schulz, G. E. (1992) J. Mol. Biol. 224, 159-177], its contribution to catalysis has not yet been demonstrated by functional studies since the proton NMR of the K21M mutant was shown to be perturbed significantly [Tian, G., Yan., H., Jiang, R.-T., Kishi, F., Nakazawa, A., & Tsai, M.-D. (1990) Biochemistry 29, 4296-4304]. We therefore undertook further structural and functional analyses of a conservative mutant K21R and a nonconservative mutant K21A. In addition to kinetic analyses, the structures of the mutants were analyzed by one- and two-dimensional proton NMR spectroscopy and (1H, 15N) heteronuclear multiple-quantum coherence (HMQC) experiments. Detailed assignments were performed in reference to the total backbone assignments of the WT AK.MgAP5A complex [Byeon, I.-J. L., Yan, H., Edison, A. S., Mooberry, E. S., Abildgaard, F., Markley, J. L., & Tsai, M.-D. (1993) Biochemistry 32, 12508-12521]. The analysis showed that the residues located near the active site (Gly15, Thr23, Arg97, Gln101, Arg128, Arg132, Asp140, Asp141, and Tyr153) exhibit greater changes in 1H-15N chemical shifts. Finally, two-dimensional 31P-31P COSY experiments were used to examine the effects of the lysine side chain on the phosphate groups in the bound AP5A. Our data have led to the following conclusions independent of the crystal structure: (i) Because the perturbations in the conformation of the mutants are not global and are mainly localized at active site residues and Tyr153, the side chain of Lys21 can be concluded to stabilize the transition state in the catalysis of AK by up to 7 kcal/mol on the basis of the 10(5)-fold decreases in the kcat/Km of mutants. (ii) The results of 31P NMR analyses suggest that Lys21 functions by orienting the triphosphate chain of MgATP to a proper conformation required for catalysis. (iii) The interaction between Lys21 and the phosphate chain in turn dictates the interactions between the substrates and the active site residues. In the K21R.MgATP complex, the NH chemical shifts of many of the active site residues are perturbed. (iv) The catalytic functions of Lys21 cannot be replaced by a conservative residue arginine. In addition, since K21A and K21R behave similarly, the catalytic function of Lys21 should not be merely a charge effect. PMID- 7880813 TI - Electrostatic effects of surface acidic amino acid residues on the oxidation reduction potentials of the flavodoxin from Desulfovibrio vulgaris (Hildenborough). AB - The flavodoxin from Desulfovibrio vulgaris (Hildenborough) is a member of a family of small, acidic proteins that contain a single noncovalently bound flavin mononucleotide (FMN) cofactor. These proteins function as low-potential one electron transferases in bacteria. A distinguishing feature of these flavoproteins is the dramatic decrease in the midpoint potential of the semiquinone/hydroquinone couple of the FMN upon binding to the apoprotein (-172 mV for FMN free in solution versus -443 mV when bound), a perturbation thought to be essential for physiological function. The structural basis of this phenomenon is not yet thoroughly understood. In this study, the contribution of six acidic residues (Asp62, Asp63, Glu66, Asp95, Glu99, and Asp106) to the perturbation of the redox properties of the cofactor has been investigated. These residues are clustered about the FMN binding site within 13 A of the N(1) atom of the cofactor. Using oligonucleotide-directed mutagenesis, these residues were neutralized in various combinations through the substitution of asparagine for aspartate and glutamine for glutamate. Seventeen mutant flavodoxins were generated in which one to all six acidic residues were systematically neutralized, often in various spatial configurations. There was no obvious correlation between the midpoint potentials for the oxidized/semiquinone couple and general electrostatic environment, although some differences were noted. However, the midpoint potential for the semiquinone/hydroquinone couple for each of the mutants was less negative than that of the wild type. These increases are strongly correlated with the number of acid to amide substitutions, with an average contribution of about 15 mV per substitution. Collectively, the unfavorable electrostatic environment provided by these acidic residues accounts for approximately one-third of the large midpoint potential shift for the semiquinone/hydroquinone couple that typifies the flavodoxin family, apparently through the destabilization of the flavin hydroquinone anion. PMID- 7880814 TI - Structural analysis of the active site of porcine pancreatic elastase based on the X-ray crystal structures of complexes with trifluoroacetyl-dipeptide-anilide inhibitors. AB - The X-ray crystal structures of two new (trifluoroacetyl)dipeptide p (trifluoromethyl)anilide (TFA-dipeptide-TFM) inhibitors complexed to porcine pancreatic elastase are presented. TFA-Val-Ala-TFM and TFA-Phe-Ala-TFM both bind to elastase with the TFA group in the S1 subsite, Val or Phe in the S2 subsite, Ala in the S3 subsite, and the TFM group in the S4 subsite. Five other TFA dipeptide-anilide/elastase crystal structures are available (two TFA-X-Ala-p (trifluoromethyl)anilide, X = Lys, Leu, and three TFA-Lys-X-p-isopropylanilide, X = Pro, Leu, Phe). The four inhibitors with the trifluoromethyl substituent on the anilide ring bind in a single mode to elastase, whereas superposition of the three inhibitors with the isopropyl substituent on the anilide ring show three different modes of binding to the protein [Mattos, C., et al. (1994) Nature Struct. Biol. 1, 55-58]. The seven structures are taken together in a detailed analysis of the active site of porcine pancreatic elastase. The inhibition constants for the inhibitors are used in combination with the crystal structures to understand the specificity of the different elastase subsites. PMID- 7880815 TI - Thermodynamic evaluation of binding interactions in the methionine repressor system of Escherichia coli using isothermal titration calorimetry. AB - The binding interactions of the methionine repressor protein, MetJ, from Escherichia coli with its cognate, metbox DNA sequence and corepressor S adenosylmethionine were examined using calorimetric methods. A detailed thermodynamic characterization of this system which exhibits the recently reported (beta alpha alpha)2 binding motif provides values for delta G, delta H, and delta S for each step in the repressor binding cycle. These studies show that, in the presence of corepressor, MetJ binds to a single metbox operator site with delta G = -7.7 kcal.mol-1, whereas in the absence of corepressor, the free energy of interaction with a single site is -5.8 kcal.mol-1. Cooperative interactions between two repressor molecules bound to two adjacent sites contribute an additional free energy of -1.3 kcal.mol-1 to binding at the second site. Binding is enthalpically unfavorable in the absence of the corepressor with delta H = +2.6 kcal.mol-1 but becomes exothermic with delta H = -4.6 kcal.mol-1 when corepressor is present. The heat capacity for the system decreases significantly by delta Cp = -290 cal.mol-1.K-1 on a per site basis when the protein binds to DNA, and interactions between repressor molecules bound to adjacent sites contribute a delta Cp = -800 cal.mol-1.K-1, indicating that solvent exclusion plays a significant role in binding in this system. The corepressor binds to the unbound repressor protein with a free energy of delta G = -6.0 kcal.mol-1 and to the MetJ-operator complex with delta G = -6.95 kcal.mol 1. Repressor binding to random-sequence DNA was estimated to occur with a free energy of -5.7 kcal.mol-1 in the presence of corepressor. These data clearly indicate that MetJ repressor dimer binds specifically to the central region of its 8 bp cognate metbox operator but recognizes partial operator sequences as short as 6 bp. Cooperativity in binding of adjacent MetJ dimers to a double metbox sequence is demonstrated to be important in determining the energetics of the interaction. Finally, the corepressor S-adenosylmethionine enhances the affinity of MetJ for its recognition site DNA by a factor of 25 and contributes significantly to the net exothermicity of repressor binding. PMID- 7880816 TI - Designing zinc-finger ADR1 mutants with altered specificity of DNA binding to T in UAS1 sequences. AB - Yeast ADR1 contains two Cys2,His2 zinc fingers needed for DNA binding to the upstream activation sequence UAS1, with bases T5T6G7-G8A9G10 in the ADH2 promoter. Potential DNA-contacting amino acid residues at -1, +3, and +6 in the alpha-helical domains of ADR1's fingers one and two include RHR-RLR; however, the latter finger two residues Leu146 and Arg149 had not proved to be crucial for ADR1 binding, even though Leu146-T6 and Arg149-T5 interactions with UAS1 DNA were predicted. We altered Leu146 or Arg149 by PCR cassette mutagenesis, to study ADR1 mutant binding to 16 UAS1 variants of thymine bases T5 and T6. Mutation of Leu146 to His, making finger two (RLR) like finger one (RHR), decreased binding to wild type UAS1 having T6, but enhanced its binding strength to sequences having purines G6 or A6, similar to binding seen between finger one's His118 and base A9 of UAS1. Mutating Leu146 to Lys caused this finger two RKR mutant to bind strongly to both G6 and T6, possibly by lysine's amine H-bonding to the carbonyl of guanine or thymine. Specificity of ADR1 for UAS1 with T6 may thus be due to hydrophobic interaction between Leu146 and the T6 methyl group. ADR1 mutants with either His or Lys in the central +3 residue (146) of zinc finger two, which have Arg149 in the +6 alpha-helical position, bind with UAS1 mutant sequences having G5 very strongly, T5 strongly, A5 intermediately, and C5 weakly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880817 TI - Resolution of the steroid-binding and dimerization domains of human sex hormone binding globulin by expression in Escherichia coli. AB - To determine the minimal sequence requirements for steroid binding and dimerization of human sex hormone-binding globulin (SHBG), the SHBG polypeptide and various SHBG deletion mutants were expressed as glutathione S-transferase (GST) fusion proteins in Escherichia coli. Fusion proteins containing the complete SHBG sequence, or the first 177 N-terminal residues of SHBG, bound steroids with high affinity and specificity. Further deletions from the C terminus severely compromised steroid-binding activity, as did N-terminal deletions beyond residue 18 in the SHBG sequence. Thus, residues 18-177 in SHBG encompass a region required for its steroid-binding activity, and a disulfide bridge normally present between Cys-164 and Cys-188 in SHBG is not obviously essential for steroid binding. Most of the GST/SHBG fusion proteins undergo cleavage at 4 degrees C, releasing immunoreactive polypeptides that correspond approximately in size to their respective SHBG sequences. The 23-kDa immunoreactive cleavage product released from the fusion protein containing residues 1-205 in the SHBG sequence (SHBG 1-205) has a 50-fold greater steroid binding capacity but a 7.5-fold lower affinity than its parent fusion protein. In addition, the 22-kDa immunoreactive polypeptide released from SHBG(1-194) binds steroid, and its dimerization is promoted by steroid ligands that bind SHBG with high affinity. These data suggest that the N-terminal region of SHBG dimerizes readily in the absence of GST and in doing so acquires steroid-binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880818 TI - Phosphorylation site mutants of the mannitol transport protein enzyme IImtl of Escherichia coli: studies on the interaction between the mannitol translocating C domain and the phosphorylation site on the energy-coupling B-domain. AB - Mannitol binding and translocation catalyzed by the C domain of the Escherichia coli mannitol transport protein enzyme IImtl is influenced by domain B. This interaction was studied by monitoring the effects of mutating the B domain phosphorylation site, C384, on the kinetics of mannitol binding to the C domain. The dissociation constants for mannitol to the C384 mutants in inside-out membrane vesicles varied from 45 nM for the wild-type enzyme to 306 nM for the mutants. The rate constants pertinent to the binding equilibrium were also altered by the mutations. The association rate of mannitol to the cytoplasmic binding site in the mutants was accelerated for all mutants. The exchange rate of bound mannitol on the wild-type enzyme was shown to be pH dependent with a pKa of approximately 8 and increasing rates at higher pH. This rate was increased for all the mutants, but the pKas differed for the various mutants. The exchange rate for binding to the isolated IICmtl, however, was not pH dependent and exhibited a low rate. Exchange measured at 4 degrees C showed that, of the two steps, binding and occlusion, involved in binding to wild-type EIImtl in inside-out vesicles, only one could be detected for the C384E and C384L mutants. This suggests that the mutations increased the rate of the occlusion step so that it was no longer separable from the initial binding step or that the mutations eliminated the occlusion step altogether. The change in the mannitol binding kinetics of the C domain indicates that the B and C domains of EIImtl influence each other's conformation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880819 TI - Local structural preferences in the alpha-lactalbumin molten globule. AB - Molten globules have been proposed to be general intermediates in protein folding. Despite numerous studies, a detailed description of the structure of a molten globule remains elusive. Recently, we showed that the molten globule formed by the helical domain of alpha-lactalbumin (alpha-LA) has a native-like backbone topology. Here we probe local structural preferences in the helical domain of the alpha-LA molten globule by analyzing a set of native and nonnative single disulfide bond variants using a combination of circular dichroism spectroscopy and determination of the equilibrium constant for disulfide bond formation. We find that the region surrounding the 28-111 disulfide bond has a high preference to adopt a native-like structure. Formation of other native or nonnative disulfide bonds is significantly less favorable. Our results suggest that molten globules contain regions with varying degrees of specificity for native-like structure and that the core region surrounding the 28-111 disulfide bond plays an important role in alpha-LA folding by stabilizing the molten globule intermediate. PMID- 7880820 TI - Metal ion activator effects on intrinsic isotope effects for hydride transfer from decarboxylation in the reaction catalyzed by the NAD-malic enzyme from Ascaris suum. AB - The mechanism of the oxidative decarboxylation reaction catalyzed by the NAD malic enzyme from Ascaris suum has been examined with several different divalent metal ion activators and dinucleotide substrates. Primary deuterium and tritium isotope effects have been obtained and, in combination with the partitioning ratios of the oxalacetate intermediate to malate and pyruvate, have been used to calculate commitment factors, intrinsic deuterium isotope effects on the hydride transfer step, and intrinsic 13C isotope effects for the decarboxylation step. A survey of malate analogs has been undertaken to define the geometry of the active site and to identify functional groups on malate important for substrate binding. With NAD as dinucleotide substrate, a direct correlation between the size of the divalent metal ion activator and the intrinsic deuterium isotope effect is observed. An isotope effect significantly greater than the semiclassical limit is seen when Cd2+ is the metal ion activator, indicating a substantial tunneling contribution. The primary intrinsic 13C isotope effect on the decarboxylation step increases over the series Mg2+ < Mn2+ < Cd2+, which is in contrast to the equal isotope effects measured for these metal ions for the nonenzymatic decarboxylation of oxalacetate [Grissom, C. B., & Cleland, W. W. (1986) J. Am. Chem. Soc. 108, 5582]. With Mn2+ or Cd2+ as the divalent metal ion activator, the data support a stepwise mechanism for the enzymatic oxidative decarboxylation with NAD as the dinucleotide substrate, but a change to a concerted mechanism is indicated with more redox-positive dinucleotide substrates as suggested previously with Mg2+ as activator [Karsten, W. E., & Cook, P. F. (1994) Biochemistry 33, 2096].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880821 TI - Structure and function in rhodopsin. Separation and characterization of the correctly folded and misfolded opsins produced on expression of an opsin mutant gene containing only the native intradiscal cysteine codons. AB - Previous mutagenesis studies have indicated the requirement of a tertiary structure in the intradiscal region with a disulfide bond between Cys-110 and Cys 187 for the correct assembly and/or function of rhodopsin. We have now studied a rhodopsin mutant in which only the natural intradiscal cysteines at positions 110, 185, and 187 are present while all the remaining seven cysteines in the wild type bovine rhodopsin have been replaced by serines. The proteins formed on expression of this mutant in COS-1 cells bind 11-cis-retinal only partially to form the rhodopsin chromophore. We show that this is due to the presence of both correctly folded chromophore-forming opsin and misfolded opsins. Methods have been devised for the separation of the correctly folded and misfolded forms by selective elution from immunoaffinity adsorbants. Using several criteria, which include SDS-PAGE as well as UV/visible and CD spectroscopy, we find that the correctly folded mutant protein is indistinguishable in its spectral properties from the wild-type rhodopsin. Further, reaction of sulfhydryl groups in the correctly folded mutant pigment with N-ethylmaleimide indicates that alkylation of a single sulfhydryl requires denaturation or illumination, while reaction with an additional two sulfhydryl groups occurs only after reduction. The misfolded mutant opsins are characterized by reduced alpha-helical content, sulfhydryl reactivity under native conditions in the dark, and also the presence of a disulfide bond.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880822 TI - Protein thermal denaturation, side-chain models, and evolution: amino acid substitutions at a conserved helix-helix interface. AB - Random mutant libraries with substitutions at the interface between the N- and C terminal helices of Saccharomyces cerevisiae iso-1-cytochrome c were screened. All residue combinations that have been identified in naturally occurring cytochrome c sequences are found in the libraries. Mutants with these combinations are biologically functional. Enthalpies, heat capacities, and midpoint temperatures of denaturation are used to determine the entropy and Gibbs free energy of denaturation (delta GD) for the ferri form of the wild-type protein and 13 interface variants. Changes in delta GD cannot be allocated solely to enthalpic or entropic effects, but there is no evidence of enthalpy-entropy compensation. The lack of additivity of delta GD values for single versus multiple amino acid substitutions indicates that the helices interact thermodynamically. Changes in delta GD are not in accord with helix propensities, indicating that interactions between the helices and the rest of the protein outweigh helix propensity. Comparison of delta GD values for the interface variants and nearly 90 non-cytochrome c variants to side-chain model data leads to several conclusions. First, hydrocarbon side chains react to burial-like transfer from water to cyclohexane, but even weakly polar side chains respond differently. Second, despite octanol being a poor model for protein interiors, octanol-to-water transfer free energies are useful stability predictors for changing large hydrocarbon side chains to smaller ones. Third, unlike cyclohexane and octanol, the Dayhoff mutation matrix predicts stability changes for a variety of substitutions, even at interacting sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880824 TI - Thermodynamics of denaturation of barstar: evidence for cold denaturation and evaluation of the interaction with guanidine hydrochloride. AB - Isothermal guanidine hydrochloride (GdnHCl)-induced denaturation curves obtained at 14 different temperatures in the range 273-323 K have been used in conjunction with thermally-induced denaturation curves obtained in the presence of 15 different concentrations of GdnHCl to characterize the thermodynamics of cold and heat denaturation of barstar. The linear free energy model has been used to determine the excess changes in free energy, enthalpy, entropy, and heat capacity that occur on denaturation. The stability of barstar in water decreases as the temperature is decreased from 300 to 273 K. This decrease in stability is not accompanied by a change in structure as monitored by measurement of the mean residue ellipticities at both 222 and 275 nm. When GdnHCl is present at concentrations between 1.2 and 2.0 M, the decrease in stability with decrease in temperature is however so large that the protein undergoes cold denaturation. The structural transition accompanying the cold denaturation process has been monitored by measuring the mean residue ellipticity at 222 nm. The temperature dependence of the change in free energy, obtained in the presence of 10 different concentrations of GdnHCl in the range 0.2-2.0 M, shows a decrease in stability with a decrease as well as an increase in temperature from 300 K. Values of the thermodynamic parameters governing the cold and the heart denaturation of barstar have been obtained with high precision by analysis of these bell-shaped stability curves. The change in heat capacity accompanying the unfolding reaction, delta Cp, has a value of 1460 +/- 70 cal mol-1 K-1 in water. The dependencies of the changes in enthalpy, entropy, free energy, and heat capacity on GdnHCl concentration have been analyzed on the basis of the linear free energy model. The changes in enthalpy (delta Hi) and entropy (delta Si), which occur on preferential binding of GdnHCl to the unfolded state, vis-a-vis the folded state, both have a negative value at low temperatures. With an increase in temperature delta Hi makes a less favorable contribution, while delta Si makes a more favorable contribution to the change in free energy (delta Gi) due to this interaction. The change in heat capacity (delta CPi) that occurs on preferential interaction of GdnHCl with the unfolded form has a value of only 53 +/- 36 cal mol-1 K-1 M-1. The data validate the linear free energy model that is commonly used to analyze protein stability. PMID- 7880823 TI - Effects of nucleotides on the protein ligands to metals at the M2 and M3 metal binding sites of the spinach chloroplast F1-ATPase. AB - We have identified the most probable protein ligands at the catalytic M3 and noncatalytic M2 metal-binding sites in the spinach chloroplast F1-ATPase (CF1) and here propose possible residues in the protein sequence for these ligands in latent CF1 in the absence of nucleotide. The changes in the metal ligands at these sites upon binding of nucleotide to the N2 and N3 sites and upon activation of latent CF1 provide a possible molecular basis for inhibition of ATPase activity by free metal, for the lack of activity in the latent state, and for the gating mechanism of the ATPase H+ pump. To these ends, the Mg2+ analogue, vanadyl (VIV = O)2+, was used as a paramagnetic probe at the M2 and M3 metal-binding sites. EPR and ESEEM spectra of VO2+ were obtained, and simulations of the full EPR spectra imply the ligand sets at the different metal-binding sites. When VO2+ is added to CF1 in the absence of ATP, the most likely set of ligands at the M2 site are 1 ROH (alpha T176), 2 H2O, and 1 RCOO- (alpha D269 or alpha D270), where the suggested amino acid designations of the residues are given in parentheses according to the mitochondrial sequence. Evidence suggests a possible axial nitrogen ligand at this site (alpha K175). When the M2 site is filled by addition of VO2+ and ATP, the metal binds as a second species in which N2-bound ATP and M2 bound VO2+ form a monodentate complex with concomitant exchange of the equatorial protein ligands by 3 H2O.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880825 TI - Properties of recombinant fluorescent proteins from Photobacterium leiognathi and their interaction with luciferase intermediates. AB - Ligand binding and luciferase interaction properties of the recombinant protein corresponding to the lumazine protein gene (EMBL X56534) of Photobacterium leiognathi have been determined by fluorescence dynamics, circular dichroism, gel filtration, and SDS-PAGE. Scatchard analysis of a fluorescence titration shows that the apoprotein possess one binding site, and at 30 degrees C the KdS (microM) are as follows: 6,7-dimethyl-8-ribityllumazine, 0.26; riboflavin, 0.53; and much more weakly bound FMN, 30. All holoproteins are highly fluorescent and have absorption spectra distinct from each other and from the free ligands. The longest wavelength absorption maxima are, respectively (nm, 2 degrees C), 420, 463, and 458. Ligand binding produces no change in the far-UV circular dichroism; all have mean residual ellipticity at 210 nm of -6500 deg cm2 dmol-1, the same as the native protein. However, in the bioluminescence reaction only the lumazine holoprotein shows a bioluminescence effect. Fluorescence emission anisotropy decay was used to establish that none of these holoproteins complexed with native luciferase and that the lumazine protein alone formed a 1:1 complex with the luciferase hydroxyflavin fluorescent transient and the luciferase peroxyflavin intermediates, revealed by a dominant channel of anisotropy loss, with rotational correlation time of 2.5 ns, and attributed to excitation transfer from the luciferase flavin donor to the acceptor, the lumazine ligand. The complex stability was sufficient to allow its isolation by FPLC gel filtration and verification by SDS-PAGE. These methods also confirmed the absence of interaction of the holoflavoproteins. PMID- 7880826 TI - Recombinant Desulfovibrio vulgaris rubrerythrin. Isolation and characterization of the diiron domain. AB - The gene encoding Desulfovibrio (D.) vulgaris rubrerythrin (Prickril, B. C., Kurtz, D. M., Jr., LeGall, J., & Voordouw, G. (1991) Biochemistry 30, 1118), a protein of unknown function containing both FeS4 and (mu-oxo)diiron sites, was cloned and overexpressed in Escherichia coli. Upon cell lysis, the overexpressed protein was found in an insoluble form deficient in iron. Iron was incorporated in vitro by dissolving the protein in 3 M guanidinium chloride, adding Fe(II) anaerobically and diluting the denaturant. This recombinant rubrerythrin was found to have properties very similar to those of rubrerythrin isolated from D. vulgaris, except that the recombinant rubrerythrin contained six rather than four (or five) iron atoms per 44 kDa homodimer. Analyses of UV-vis, Mossbauer, and EPR spectra showed that the six iron atoms in recombinant rubrerythrin are organized as two FeS4 and two (mu-oxo/hydroxo)diiron sites. In order to allow examination of the diiron sites in the absence of the FeS4 sites, a truncated gene encoding the N-terminal 152 residues of D. vulgaris rubrerythrin was also cloned and overexpressed as an insoluble protein in E. coli, and iron was incorporated by a procedure analogous to that for recombinant rubrerythrin. This so-called "chopped" rubrerythrin (CRr) was found to consist of an approximately 35 kDa homodimer containing four iron atoms. Spectroscopic characterization indicated that the four iron atoms in CRr are organized as two diiron sites, the majority of which closely resemble the (mu-oxo)diiron(III) sites in E. coli ribonucleotide reductase R2 protein, and a minor fraction of which resemble the mixed-valent diiron(II,III) site in methane monooxygenase hydroxylase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880827 TI - Site-directed mutagenesis of Lys36 in human thioredoxin: the highly conserved residue affects reduction rates and growth stimulation but is not essential for the redox protein's biochemical or biological properties. AB - Previous studies have demonstrated that a recombinant form of the human redox protein thioredoxin can stimulate the growth rate of Swiss 3T3 murine fibroblasts and that this ability to promote cellular proliferation was dependent upon a redox-active form. A site-directed mutagenesis study of the highly conserved Lys36 adjacent to the two active site cysteines of thioredoxin was performed to determine whether the basic residue was essential for the biochemical and mitogenic properties of human thioredoxin. Two mutants were generated in which the lysine residue was replaced with either glutamic acid (K36E) or leucine (K36L). While K36E and K36L were both redox-active in a thioredoxin-specific assay, the mutants exhibited decreased affinities for thioredoxin reductase relative to wild-type thioredoxin since their respective KM values increased by a factor of 5 and 7. Examination of the secondary structure of the variants by circular dichroism spectroscopy revealed that both mutants had minor variations in the overall structural content when compared to thioredoxin, with K36L being most similar to the wild-type protein. Thermal equilibrium denaturation studies of the variants showed that K36E had a TM of 69.5 degrees C. A TM value for thioredoxin and K36L could not be established because the absence of a plateau above 83 degrees C rendered it difficult to establish an upper base line and, hence, the TM. The two mutants were able to stimulate cellular proliferation, albeit with reduced efficiency when compared with wild-type thioredoxin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880828 TI - The catalytic outcomes of the constitutive and the mitogen inducible isoforms of prostaglandin H2 synthase are markedly affected by glutathione and glutathione peroxidase(s). AB - Reduced glutathione (GSH), at physiological concentrations, was found to markedly alter the profile of arachidonate metabolism by prostaglandin H2 synthase. In 1 mM GSH, the constitutive (COX-1) and the mitogen inducible (COX-2) isoforms metabolized arachidonate to 12-hydroxyheptadecatrienoic acid (12-HHT) (88% and 78% of total products, respectively). Prostanoid formation was consequently reduced to only 12% (COX-1) and 19% (COX-2) of the total metabolites. The GSH dependent production of 12-HHT was regio- and enantioselective for the 12(S) isomer. We propose that 12(S)-HHT is formed by a GSH-dependent enzymatic cleavage of the PGH2 8,9 and 11,12 carbon-carbon bonds based on the following: (a) nonsignificant GSH-dependent formation of 12(S)-HHT during chemical decomposition of synthetic PGH2, (b) the structural similarities between the asymmetric carbons at C(12) in 12-HHT and C(15) in PGH2, (c) the GSH concentration-dependent product/precursor relationship between 12-HHT and prostanoid production, and (d) aspirin inhibition of 12-HHT formation by both enzymes. Arachidonic acid oxidation by COX-1, and not by COX-2, was inhibited by the combined presence of GSH and liver cytosol. In contrast, metabolism by neither isoform was inhibited when the cytosol was obtained from selenium-depleted animals. This is consistent with a unique, selenium dependent, cytosolic GSH peroxidase that inhibits specifically prostanoid and 12(S)-HHT formation by COX-1. These results suggest an additional role for GSH and GSH peroxidase(s) in regulating prostanoid biosynthesis. Differences between the isoforms in their sensitivities to GSH peroxidase may reflect differences in their requirements for an "initiator hydroperoxide". PMID- 7880829 TI - Phosphorylation of the multidrug resistance associated protein gene encoded protein P190. AB - Recent studies suggest that multidrug resistance of HL60/ADR cells is related to an overexpression of the MRP (multidrug resistance associated protein) gene which encodes a 190-kDa ATP-binding membrane glycoprotein. In the present study we have further characterized P190 and have examined phosphorylation properties of the protein. The results demonstrate that P190 is highly phosphorylated and that the phosphate groups are metabolically active and undergo cycles of phosphorylation and dephosphorylation in the cell. Serine is the single amino acid phosphorylated in P190 and the phosphate groups are contained in nine tryptic peptides. Experiments have also been conducted to analyze the effect of various protein kinase inhibitors on phosphorylation levels of P190. The results show that H-7, staurosporine, and chelerythrine can reduce the phosphorylation of this protein. In the presence of both H-7 (200 microM) and staurosporine (200 nM) the phosphorylation of P190 is completely blocked. It has also been found that in the presence of these agents there is a major increase in drug accumulation and concomitant inhibition in drug efflux of resistant cells. These results therefore suggest the possibility that certain phosphate groups of protein P190 play an important role in modulating drug accumulation in resistant cells. PMID- 7880830 TI - Critical side-chain interactions at a subunit interface in the Arc repressor dimer. AB - In the Arc repressor dimer, the side chains of Ile37 and Val41 in alpha-helix B pack against each other and against the symmetry-related side chains of Ile37' and Val41' in alpha-helix B' to form part of the hydrophobic core and the dimer interface. Following combinatorial mutagenesis of these positions, only the wild type combination of hydrophobic residues was recovered as a fully active protein, and only a few conservative replacements were recovered as stably folded or partially active proteins. Equilibrium and kinetic studies of the folding of purified mutants show that the delta-CH3 groups of Ile37 and Ile37' contribute approximately 2 kcal/mol of dimer to protein stability and are involved in interactions that are only partially formed in the transition state for protein folding. Alanine substitution at either position 37 or 41 results in proteins which differ from wild type in being monomeric at a concentration of 10 microM, having reduced secondary structure, having solvent-exposed tryptophans, and showing non-cooperative thermal and urea denaturation transitions. These mutants appear to exist in a physiologically denatured state that is similar in many ways to the molten globule state. PMID- 7880831 TI - 2-Amino-3-ketobutyrate-CoA ligase from beef liver mitochondria: an NMR spectroscopic study of low-barrier hydrogen bonds of a pyridoxal 5'-phosphate dependent enzyme. AB - A study of protons associated with low-barrier hydrogen bonds in 2-amino-3 ketobutyrate-CoA ligase (AKB-ligase, EC 2.3.1.29) by NMR is reported. Three resonances are observed in the range of delta H = 15-20 ppm when the NMR spectrum of AKB-ligase is recorded at 600 MHz. These low-barrier hydrogen bonds are associated respectively with a side chain proton, the PLP pyridinium ring nitrogen proton, and the PLP Schiff base proton at the active site of the ligase. The pyridinium proton has been assigned a chemical shift of 19.10 ppm and the Schiff base proton 14.90 ppm. The third low-barrier hydrogen bond associated proton resonating at 16.20 ppm is assigned to a proton of a side chain group. All three resonances disappear when pyridoxal phosphate is removed from the ligase. Consistent with NOE coupling, the side chain group proton should be close to the proton of the Schiff base nitrogen of the pyridoxal 5'-phosphate. The effects of temperature, pH, substrate, and NOE on the three resonances are also studied, in order to assign the protons. The three low-barrier hydrogen bonds described in this report may serve to anchor the cofactor in the active site of 2-amino-3 ketobutyrate-CoA ligase. PMID- 7880832 TI - Site-directed mutations in tyrosine 195 of cyclodextrin glycosyltransferase from Bacillus circulans strain 251 affect activity and product specificity. AB - Tyrosine 195 is located in the center of the active site cleft of cyclodextrin glycosyltransferase (EC 2.4.1.19) from Bacillus circulans strain 251. Alignment of amino acid sequences of CGTases and alpha-amylases, and the analysis of the binding mode of the substrate analogue acarbose in the active site cleft [Strokopytov, B., et al. (1995) Biochemistry 34, (in press)], suggested that Tyr195 plays an important role in cyclization of oligosaccharides. Tyr195 therefore was replaced with Phe (Y195F), Trp (Y195W), Leu (Y195L), and Gly (Y195G). Mutant proteins were purified and crystallized, and their X-ray structures were determined at 2.5-2.6 angstrum resolution, allowing a detailed comparison of their biochemical properties and three-dimensional structures with those of the wild-type CGTase protein. The mutant proteins possessed significantly reduced cyclodextrin forming and coupling activities but were not negatively affected in the disproportionation and saccharifying reactions. Also under production process conditions, after a 45 h incubation with a 10% starch solution, the Y195W, Y195L, and Y195G mutants showed a lower overall conversion of starch into cyclodextrins. These mutants produced a considerable amount of linear maltooligosaccharides. The presence of aromatic amino acids (Tyr or Phe) at the Tyr195 position thus appears to be of crucial importance for an efficient cyclization reaction, virtually preventing the formation of linear products. Mass spectrometry of the Y195L reaction mixture, but not that of the other mutants and the wild type, revealed a shift toward the synthesis (in low yields) of larger products, especially of beta- and gamma- (but no alpha-) cyclodextrins and minor amounts of delta-, epsilon-, zeta- and eta-cyclodextrins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880833 TI - Covalent sequestration of melphalan by metallothionein and selective alkylation of cysteines. AB - Rabbit liver metallothionein-2 is shown to form covalent bonds with the anticancer agent melphalan, in support of the hypothesis that covalent sequestration by metallothionein constitutes one mechanism for the cross resistance acquired by cancer patients to therapeutic alkylating agents. Among 20 cysteines in the 2-domain protein, 89% of the first alkylation reaction occurs with 2 that cochelate a zinc cation in the carboxy domain. Computer-supported docking studies indicate a favorable binding site for melphalan near these cysteine sulfhydryl groups. Although folded metallothionein-2 is resistant to trypsin cleavage, alkylation by 1 mol of melphalan allows cleavage by trypsin between the two globular domains. PMID- 7880834 TI - Characterization of a Thermomonospora fusca exocellulase. AB - The exocellulase E3 gene was cloned on a 7.1 kb NotI fragment from Thermomonospora fusca genomic DNA into Escherichia coli and expressed in Streptomyces lividans. The E3 gene was sequenced and encoded a 596 residue peptide. The molecular masses of the native and cloned E3s were determined by mass spectrometry, and the value for E. coli E3, 59,797 Da, agreed well with that predicted from the DNA sequence, 59,646 Da. The value of 61,200 Da for T. fusca E3 is consistent with E3 being a glycoprotein. E3 is thermostable, retaining full activity after 16 h at 55 degrees C. It also has a broad pH optimum around 7-8, retaining 90% of its maximal activity between pH 6 and 10. The cloned E3s were identical to the native enzyme in their activity, cellulose binding, and thermostability. Papain digestion produced a 45.7 kDa catalytic domain with 77% of the native activity on amorphous cellulose and 33% on crystalline cellulose. E3 belongs to cellulase family B and retains the residues that have been identified to be crucial for catalytic activity in Trichoderma reesei cellobiohydrolase II and T. fusca E2. The E3 gene contains a 14 bp inverted repeat regulatory sequence 212 bp before the translational start codon instead of the 30-70 bp found for the other T. fusca cellulase genes. An additional copy of this sequence with one base changed is 314 bp before the translational start codon. The transcriptional start site of the E3 gene was shown to be between these two inverted repeats. PMID- 7880835 TI - The catalytic role of aspartic acid-92 in a human dual-specific protein-tyrosine phosphatase. AB - The mechanism of catalysis for the human dual-specific (vaccinia H1-related) protein-tyrosine-phosphatase was investigated. The pH dependence of the kcat value is bell-shaped when p-nitrophenyl phosphate was employed as a model substrate. The kcat/Km pH profile rises with a slope of 2 and decreases with a slope of -1, indicating that two groups must be unprotonated and one group must be protonated for activity. An amino acid residue with an apparent pKa value of 5.5 +/- 0.2 must be unprotonated and a residue with a pKa value of 5.7 must be unprotonated for activity. The pKa value of the catalytic cysteine-124 (C124) was 5.6 +/- 0.1. The aspartic acid-92-asparagine (D92N) mutant enzyme was 100-fold less active than the native enzyme and exhibited the loss of the basic limb in the pH profiles, suggesting that in the native enzyme D92 must be protonated for activity. The D92 residue is conserved throughout the entire family of dual specific phosphatases. Mutants glutamic acid-6-glutamine, glutamic acid-32 glutamine, aspartic acid-14-asparagine, and aspartic acid-110-asparagine had less than a 2-fold effect on the kinetic parameters when compared to native enzyme. Based upon the lack of a "burst" in rapid reaction kinetics, formation of the intermediate is rate-limiting with both native and D92N mutant enzymes. In agreement with rate-limiting formation of the intermediate, the pKa value of 5.5 for the group which must be unprotonated for activity was assigned to C124.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880836 TI - Interaction of manganese-mesoporphyrin with oleic acid vesicles. AB - We investigated the interaction between manganese(III)mesoporphyrin (MnMeso), a metalloporphyrin, and liposome membranes containing oleic acid (OA; cis-9 octadecenoic acid). MnMeso associates preferentially with OA but minimally with egg phosphatidylcholine (EPC). Using small unilamellar vesicles, we characterized the MnMeso-OA binding at neutral pH. Our data suggest that MnMeso binds to the OA bilayer with Kd = 6.8 x 10(-4) M; the binding stoichiometry of MnMeso-OA was 1:3.4. This OA-MnMeso interaction was analyzed further for changes in the T1 relaxation property of MnMeso. OA increased the T1 of MnMeso significantly more than did EPC, suggesting that the OA-MnMeso interaction was stronger than that of PC-MnMeso. The side-chain specificity of the OA interaction with this porphyrin derivative was further supported in an experiment with manganese mesotetra(4 sulfonatophenyl)porphine, which lacks hydrophobic side chains for OA interaction. The association of MnMeso with the OA membrane was proposed according to the structure of MnMeso and OA and further verified using electron microscopy. A strong association of MnMeso with OA, an absorption enhancer of the gastrointestinal tract, may be useful for delivery of MnMeso as an oral contrast agent for magnetic resonance imaging. PMID- 7880837 TI - Insertion of the polytopic membrane protein lactose permease occurs by multiple mechanisms. AB - The lactose permease of Escherichia coli has 12 transmembrane hydrophobic domains in probable alpha-helical conformation connected by hydrophilic loops. Previous studies [Consler, T. G., Persson, B., et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 6934-6938] demonstrate that a peptide fragment (the XB domain) containing a factor Xa protease site immediately upstream of a biotin acceptor domain can be engineered into the permease, thereby allowing rapid purification to a high state of purity. Here we describe the use of the XB domain to probe topology and insertion. Cells expressing permease with the XB domain at the N terminus, at the C terminus, or in loop 6 or 10 on the cytoplasmic face of the membrane catalyze active transport, although only the chimeras with the XB domain at the C terminus or in loop 6 are biotinylated. In contrast, chimeras with the XB domain in periplasmic loop 3 or 7 are inactive, but strikingly, both constructs are biotinylated. Furthermore, the XB domain in all the constructs, particularly in the loop 3 and loop 7 chimeras, is accessible from the cytoplasmic face of the membrane, as evidenced by factor Xa proteolysis or avidin binding studies with spheroplasts and disrupted membrane preparations. Finally, alkaline phosphatase fusions one loop downstream from each periplasmic XB domain exhibit high phosphatase activity. Thus, the presence of the XB domain in a periplasmic loop apparently blocks translocation of a discrete segment of the permease consisting of the loop and the two adjoining helices without altering insertion of the remainder of the protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880838 TI - The c-myc promoter binding protein (MBP-1) and TBP bind simultaneously in the minor groove of the c-myc P2 promoter. AB - The c-myc promoter binding protein (MBP-1) is a DNA binding protein which negatively regulates the expression of the human c-myc gene. MBP-1 binds to a sequence which overlaps the binding site for the general transcription factor TBP, within the c-myc P2 promoter region. Since TBP binds in the minor groove, MBP-1 might inhibit c-myc transcription by preventing the formation of a functional preinitiation complex. In support of this hypothesis, we have demonstrated that MPB-1 is a minor groove binding protein. In order to characterize MBP-1 binding, we substituted A-T base pairs in the MBP-1 binding site with I-C base pairs, which changes the major groove surface without altering the minor groove surface. This substitution did not inhibit the sequence-specific binding of MBP-1 and TBP. On the other hand, G-C to I-C substitution within the MBP-1 binding site alters the minor groove and prevents MBP-1 binding. Competitive electrophoretic mobility shift assays were used to show that berenil, distamycin, and mithramycin, all of which bind in the minor groove, compete with MBP-1 for binding to the MPB-1 binding site. These minor groove binding ligands also effectively inhibit the simultaneous DNA binding activity of both MBP-1 and TBP. We conclude that both MBP-1 and TBP can bind simultaneously in the minor groove of the TATA motif on the c-myc P2 promoter. This suggests that MBP-1 may negatively regulate c-myc gene expression by preventing efficient transcription initiation. PMID- 7880839 TI - Conductance change in phospholipid bilayer membrane by an electroneutral ionophore, monensin. AB - Monensin is a polyether antibiotic ionophore and is considered an electroneutral Na/H antiporter. Its addition, however, increased the conductance of phospholipid bilayer membrane, and this increase was observed only when the medium contained Na+. Analysis of the current-voltage curve suggested that the increase was due to the formation and the translocation of an univalently charged species. The conductance at zero external voltage was proportional to the second power of monensin concentration and increased with the decrease in pH of the medium. Modified monensin whose terminal carboxyl was esterified showed much larger increase (ca. 100 times) in conductance than intact monensin. We concluded that the complex between the dimer of protonated monensin and Na+ contributed to the electrogenic transport of monensin. This complex bears a +1 charge, which is consistent with the analysis of current-voltage curves. Contrary to the conductance, the Na+ transfer rate of liposomal membrane measured with 23Na-NMR was proportional to the monensin concentration, meaning that the electrogenic component contributes little to the total monensin-mediated Na+ transport in the present system. It should be noted that this electrogenic component may change the membrane potential. PMID- 7880840 TI - Benzothiazepine binding domain of purified L-type calcium channels: direct labeling using a novel fluorescent diltiazem analogue. AB - We have synthesized a series of N-propylamino-substituted benzazepinones (NPSBs) as specific probes for the benzothiazepinone (BTZ) binding domain of muscle L type calcium channels (LTCCs). NPSBs were identified which possess high affinity for the channel after purification. We synthesized a fluorescent NPSB, DMBODIPY BAZ, as the first benz(othi)azepinone derivative known to reversibly label partially purified LTCCs. DMBODIPY-BAZ binds to the partially purified channel with high affinity (Kd = 25 nM, Bmax = 580 pmol/mg of protein). Fluorescence resonance energy transfer (FRET) occurred between tryptophan residues of the channel protein and the DMBODIPY fluorophore upon specific drug binding. FRET was exploited to allow highly time-resolved detection of specific drug binding kinetics. We found that the dissociation half-life (t1/2) of DMBODIPY-BAZ decreased with the concentration of an unlabeled competitor, which indicates ligand-induced accelerated dissociation. In contrast, t1/2 was concentration dependently increased by the dihydropyridine (DHP) (+)-isradipine. These kinetic properties of DMBODIPY-BAZ indicate that a high-affinity BTZ binding domain also exists on purified LTCCs. NPSBs represent novel tools to provide further insight into the molecular pharmacology of the BTZ binding domain on LTCCs. PMID- 7880842 TI - Heparin binding site, conformational change, and activation of antithrombin. PMID- 7880841 TI - Mutagenesis of the H-ras p21 at glycine-60 residue disrupts GTP-induced conformational change. AB - The function of Gly-60, the conserved glycine in the DXXG domain of v-H-ras, was examined by site-directed mutagenesis. It was found that while the G60A (Gly-60 to Ala substitution) mutation has little effect on the interaction of H-ras with guanine nucleotides, it completely abolishes the biological activity of v-H-ras. The G60A mutation also exerts little effect on the interaction of H-ras with SDC25C (a guanine nucleotide exchange factor) and GAP. However, the G60A mutation does lower the ability of H-ras to bind Raf. GTP induces an enhancement of fluorescence emission in complexes consisting of H-ras and the fluorescent dye 8 anilino-1-naphthalenesulfonic acid. This enhancement is blocked by the G60A mutation. On the basis of these observations, we propose that the GTP-induced conformational change of H-ras, a process required for H-ras activities, is impaired by the G60A mutation. PMID- 7880843 TI - Withdrawal of nursing services: strategies for survival. AB - In recent years, nursing strikes have become more common. Within the last decade, nurses in five of our ten provinces have all taken strike action. If this trend continues, more strikes could very likely occur. Administrative nurses provide direction and leadership for the nursing department. With the prospect of a withdrawal of nursing services, they are key players in preparing for the strike. They must ensure a standard of care during the strike, as well as facilitate the return of the unionized nurses following the strike. To assist administrative nurses who may some day be involved in a withdrawal of nursing services, this manuscript contains an account of the pre-strike preparations, putting these plans into action during the strike, and the immediate post-strike period at the Plains Health Centre, a tertiary care facility in Regina, Saskatchewan. PMID- 7880844 TI - The Delphi methodology (Part one): A useful administrative approach. AB - The Delphi methodology is used to determine, predict and explore group attitudes, needs and priorities. This paper, the first of a two part series on the Delphi methodology, will provide nurse administrators with the basic information necessary to participate in and conduct projects using the Delphi methodology. The methodology will be defined and issues related to design, sampling, instrumentation and methods of data analysis discussed. The role of the nurse administrator, when the Delphi methodology is used, will then be addressed. In the second paper, administrative applications of the Delphi methodology will be addressed. PMID- 7880845 TI - Job satisfaction, propensity to leave and burnout in RNs and RNAs: a multivariate perspective. AB - This investigation used a multivariate approach to examine similarities and differences between the job satisfaction, propensity to leave, and burnout of registered nurses (RNs) (n = 623) and registered nursing assistants (RNAs) (n = 231). At best, both groups were only moderately satisfied with their jobs, and there were no significant differences between the groups on the outcome measures of satisfaction, burnout or propensity to leave. However, RNs with more years of work experience reported highest job satisfaction, lowest levels of burnout, and were less likely to leave their positions. None of these variables were related to the length of time RNAs were employed. When comparative analyses were conducted by unit types, RNs in psychiatric settings were least satisfied with their jobs, more likely to leave their positions, and reported more burnout than did RNs in other settings. Implications of the study for interventions and future research are discussed. PMID- 7880846 TI - Public attitudes towards end-of-life treatment decisions: implications for nurse clinicians and nursing administrators. AB - As medical technology becomes more sophisticated, end-of-life treatment decisions become more complex for patients and for the professionals who care for them. The authors surveyed 448 members of the general public to determine their attitudes regarding end-of-life treatment decisions and attitudes towards the provision of advance end-of-life directives. A slight minority of respondents indicated they would leave major decisions to their physicians. An overwhelming majority believe that living wills are important. Most respondents indicated they would not wish their lives to be prolonged if elderly and ill or if their minds failed. A majority of respondents also were in favour of donating their organs after death. The article reports the socio demographic variables which significantly influenced these responses and suggests the implications of these results for nurse clinicians and for nursing administrators. Enhancing clients' abilities to communicate their wishes and being sensitive to social-cultural differences in perspectives about these issues, are key implications for nurse clinicians. Ensuring sound policies and guidelines are developed and that adequate education is provided in ethical and legal dimensions surrounding end-of-life treatment directives, as well as multi-cultural orientation, are responsibilities for nursing administrators. PMID- 7880847 TI - Issues in the use of the Alberta Patient Classification System to fund Ontario long term care. AB - The purpose of this paper is to assess some of the issues surrounding the use of the Alberta Patient Classification System for Long Term Care Facilities (APCS) to fund Ontario long term care by attempting to answer the following questions: 1) Is the APCS valid for classifying Ontario long term care patients?; 2) Is it appropriate to use the APCS to fund Ontario long term care?, and; 3) What is required to develop a valid long term care patient classification and funding system appropriate for Ontario? The paper discusses why it may be inappropriate to use the APCS to classify Ontario long term care patients, some of the important financial consequences to a long term care facility if the APCS is inappropriate, and what might be necessary for a better patient classification and funding strategy. The potential and pitfalls of adopting patient classification systems developed in a different health system should be of interest to nurse managers in all provinces. PMID- 7880848 TI - Research utilization in maternal-child nursing: application of the CURN model. AB - Nursing administrators, educators and clinicians are continually striving to incorporate research into practice. A number of research utilization models have been developed to help meet this challenge. This article describes how the Conduct and Utilization of Research in Nursing (CURN) approach was used in a maternal-child area of a Canadian tertiary care hospital. One patient care problem was identified by practising nurses that required acquisition and application of recent research findings. A thorough literature search and critique was conducted based on this patient care problem and research results were used to develop nursing care guidelines for this priority concern. PMID- 7880849 TI - ADP controls the electrogenicity of Na/Na exchange catalyzed by dog kidney Na,K ATPase proteoliposomes. AB - Sodium pump mediated Na/Na exchange was studied using Na(+)-loaded proteoliposomes prepared from dog kidney Na,K-ATPase. Measurements of both 22Na+ influx and pump-generated electrical potentials were carried out, the latter using the anionic dye, oxonol VI. In the presence of ATP, the formation of a strophanthidin-sensitive membrane potential confirms that Na/Na exchange associated with ATP hydrolysis can be electrogenic depending on the source of the enzyme. With the addition of varying concentrations of ADP, electrogenic exchange is progressively inhibited and replaced by electroneutral exchange. ADP is equally effective in activating (ATP + ADP)-dependent electroneutral exchange. With sufficient ADP, electrogenic Na/Na exchange is completely replaced by electroneutral exchange. PMID- 7880850 TI - Reversibility of Na+/Mg2+ antiport in rat erythrocytes. AB - Rat erythrocytes loaded with Mg2+ plus Na+ performed Mg2+ uptake under an intracellular/extracellular Na+ gradient. Mg2+ uptake was coupled to Na+ release at a stoichiometric ratio of 1 Mg2+/2 Na+.Mg2+ uptake was inhibited by amiloride, imipramine and quinidine. Mn2+ was taken up by the same transporter as Mg2+. Similar results had been found for net Mg2+ efflux via Na+/Mg2+ antiport in such rat erythrocytes. Hence, it can be concluded that Na+/Mg2+ antiport in Mg(2+) loaded rat erythrocytes operates reversibly according to the direction of the Na+ gradient which is a contributing driving force. Net Mg2+ influx was dependent on ATP which increased the affinity of intracellular Mg2+ by activating Na+/Mg2+ antiport. Mg2+ uptake was increased by phorbol ester and inhibited by staurosporine, indicating that ATP may function via protein phosphorylation by protein kinase C. PMID- 7880851 TI - H(+)-coupled alpha-methylaminoisobutyric acid transport in human intestinal Caco 2 cells. AB - Transepithelial apical-to-basal transport and cellular uptake of the non metabolisable amino acid alpha-methylaminoisobutyric acid (MeAIB) across confluent monolayers of the human intestinal epithelial cell line Caco-2 are enhanced by a transepithelial pH gradient (apical pH 6.0, basolateral pH 7.4). In Na(+)-free conditions (apical pH 7.4, basolateral pH 7.4), net absorption (120 +/ 58 pmol/cm2 per h, n = 13) and uptake across the apical membrane (cell/medium ratio 0.56 +/- 0.06, n = 13) are low. However, in Na(+)-free conditions with apical pH 6.0, net absorption (685 +/- 95 pmol/cm2 per h, n = 15) and intracellular accumulation (cell/medium ratio 3.63 +/- 0.29, n = 14) were marked. Continuous monitoring of intracellular pH (pHi) in BCECF (2',7'-bis(2 carboxyethyl)-5(6)-carboxyfluorescein)-loaded Caco-2 cell monolayers indicated that apical addition of MeAIB (20 mM) was associated with H(+)-flow across the apical membrane in both Na+ and Na(+)-free conditions. This transport process is rheogenic in Na(+)-free media, stimulating an inward short-circuit current in voltage-clamped Caco-2 cell monolayers. On the basis of competition for MeAIB accumulation and pHi experiments, L-proline, glycine, L-alanine and beta-alanine are also substrates for H(+)-linked transport at the apical membrane of Caco-2 cells but L-valine, L-leucine and L-phenylalanine are not. These data are consistent with the expression, in the apical brush-border membrane of Caco-2 cells, of a H(+)-coupled, Na(+)-independent MeAIB carrier. PMID- 7880852 TI - Export of steryl esters from lipid particles and release of free sterols in the yeast, Saccharomyces cerevisiae. AB - Fatty acyl esters of the yeast specific sterol, ergosterol, are exclusively stored in lipid particles. Under conditions of sterol deficiency, e.g., in the presence of terbinafine, an inhibitor of fungal squalene epoxidase, steryl esters are hydrolyzed, and sterols are set free for membrane formation. Lipid particles do not contain steryl-ester hydrolase activity themselves; the highest specific activity of this enzyme is found in the plasma membrane. Therefore, steryl esters have to be exported from lipid particles to their site of hydrolytic cleavage. This process of translocation and metabolic conversion was studied in vivo. Addition of nocodazole to terbinafine-treated cells did not disturb the mobilization of steryl esters, indicating that this process is not mediated by microtubuli-dependent vesicle flux. Under the influence of inhibitors of cellular energy production (azide and fluoride) and protein biosynthesis (cycloheximide) mobilization of steryl esters came to an halt. These results support the view that ongoing membrane proliferation may be a driving force for the release of sterols from steryl esters of lipid particles. PMID- 7880854 TI - Energy-dispersive X-ray reflectivity study of the model membranes at the air/water interface. AB - The results of the first energy-dispersive reflectivity measurements with a (membrane coated) liquid surface are reported. They rely on the calibration curve measured with pure water and can be done without any sample or detector movement with a low-intensity, laboratory-based X-ray generator within less than 1 h. As an illustration, the structural parameters of a diarachidoylphosphatidylcholine monolayer at the air/water interface are determined. It is argued that the energy dispersive detection in combination with the intense synchrotron radiation can be used for the time-resolved reflectivity measurements on the time-scale of minutes. PMID- 7880853 TI - Mutations of G158 and their second-site revertants in the plasma membrane H(+) ATPase gene (pma1) in Saccharomyces cerevisiae. AB - A G158D mutation residing near the cytoplasmic end of transmembrane segment 2 of the H(+)-ATPase from Saccharomyces cerevisiae appears to alter electrogenic proton transport by the proton pump (Perlin et al. (1988) J. Biol. Chem. 263, 18118-18122.) The mutation confers upon whole cells a pronounced growth sensitivity to low pH and a resistance to the antibiotic hygromycin B. The isolated enzyme retains high activity (70% of wild type) but is inefficient at pumping protons in a reconstituted vesicle system, suggesting that this enzyme may be partially uncoupled (Perlin et al. (1989) J. Biol. Chem. 264, 21857 21864). In this study, the acid-sensitive growth phenotype of the pma1-D158 mutant was utilized to isolate second site suppressor mutations in an attempt to probe structural interactions involving amino acid 158. Site-directed mutagenesis of the G158 locus was also performed to explore its local environment. Nineteen independent revertants of pma1-G158D were selected as low pH-resistant colonies. Four were full phenotypic revertants showing both low pH resistance and hygromycin B sensitivity. Of three full revertants analyzed further, one restored the original glycine residue at position 158 while the other two carried compensatory mutations V336A or F830S, in transmembrane segments 4 and 7, respectively. Partial revertants, which could grow on low pH medium but still retained hygromycin B resistance, were identified in transmembrane segments 1 (V127A) and 2 (C148T, G156C), as well as in the cytoplasmic N-terminal domain (E110K) and in the cytoplasmic loop between transmembrane segments 2 and 3 (D170N, L275S). Relative to the G158D mutant, all revertants showed enhanced net proton transport in whole-cell medium acidification assays and/or improved ATP hydrolysis activity. Small polar amino acids (Asp and Ser) could be substituted for glycine at the 158 position to produce active, albeit somewhat defective, enzymes; larger hydrophobic residues (Leu and Val) produced more severe phenotypes. These results suggest that G158 is likely to reside in a tightly packed polar environment which interacts, either directly or indirectly, with transmembrane segments 1, 4 and 7. The revertant data are consistent with transmembrane segments 1 and 2 forming a conformationally sensitive helical hairpin structure. PMID- 7880855 TI - Cloning of a swelling-induced chloride current related protein from rabbit heart. AB - Recently, pIcln has been reported to be a regulator of a swelling-induced chloride conductance. We have cloned a cDNA RCL-H1 from rabbit heart, of which primary structure is highly homologous to that of pIcln. Outwardly rectifying currents were recorded in oocytes expressing RCL-H1, which is consistent with the result of pIcln. RNA blot analysis revealed the widespread expression of RCL-H1 mRNA in rabbit tissues. RCL-H1 may play an important role in regulating cell volume and give a clue to revealing molecular structure of swelling-induced chloride channel(s). PMID- 7880856 TI - Riboflavin uptake by native Xenopus laevis oocytes. AB - The existence of a membrane-associated uptake carrier for riboflavin (RF) is demonstrated in Xenopus oocytes. Uptake of low (0.017 microM) and high (3 microM) concentrations of RF was linear with time for up to 2 hours, and occurred with little initial binding to oocytes, and little metabolism. Uptake of RF was found to be independent of extracellular pH and Na+. The initial rate of RF uptake was saturable as a function of concentration with an apparent Km of 0.41 +/- 0.02 microM and a Vmax of 2.86 +/- 0.04 fmol/oocyte per h. Uptake of 3H-RF was inhibited by unlabeled RF and by the structural analogs lumiflavin, isoriboflavin (iso-RF), 8-aminoriboflavin (8-NH2-RF), 8-hydroxyriboflavin (8-OH-RF), and lumichrome, but was not affected by flavin adenine dinucleotide (FAD), D-ribose or lumazine. Uptake of RF was significantly retarded by the metabolic inhibitor 2,4-dinitrophenol. The sulfhydryl group-modifying reagents p chloromercuriphenylsulfonate (pCMPS), p-chloromercuribenzoate (pCMB), N ethylmaleimide and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-Cl) all caused significant inhibition in RF uptake. The inhibitory effect of pCMPS was completely reversed by treatment of pCMPS-pretreated cells with reducing agents. While the transmembrane transport inhibitors 4-acetamido-4' isothiocyanatostilbene-2,2'-disulfonic acid (SITS), 4,4'-diisothiocyanatostilbene 2,2'-disulfonic acid (DIDS) and furosemide had no effect on RF uptake, amiloride and probenecid suppressed RF uptake in a dose-dependent fashion. Closer examination of the inhibition mediated by amiloride showed that it was competitive in nature with an apparent Ki of approximately 1.8 mM, whereas the inhibition induced by probenecid was nonspecific. Together, these findings indicate that Xenopus oocytes possess an endogenous, specific, membrane associated carrier-mediated uptake system for RF. The results also demonstrate the usefulness of Xenopus oocytes as a model system with which to study the RF transport event across biological membranes, which should further out present understanding of RF uptake by various vertebrate cells. PMID- 7880857 TI - Effect of membrane surface potential on the uptake and the inhibition of cationic compounds in rat intestinal brush-border membrane vesicles and liposomes. AB - The effect of membrane surface potential on the uptake of tryptamine, an organic cation, by rat intestinal brush-border membrane vesicles was investigated. In the presence of an inside-negative K(+)-diffusion potential, the manner of initial uptake of tryptamine appeared to be pH-dependent and the uptake in the acidic medium was lower than that in the neutral medium. Changes in surface potential of brush-border membrane vesicles were monitored using 8-anilino-1 naphthalenesulfonic acid (ANS) and the results suggested that the membrane surface potential (negative charge on the membrane surface) decreased in the acidic medium. A good correlation was observed between the K(+)-diffusion potential-dependent uptake of tryptamine and membrane surface potential monitored by ANS at various pH levels. The uptake of tryptamine by liposomes (large unilamellar vesicles), which contained various amounts of dipalmitoylphosphatidylserine (DPPS), was also examined. The uptake of tryptamine decreased with a decrease of DPPS content in the liposomes, and was correlated with the membrane surface potential monitored by ANS. Moreover, the effect of organic cations on the uptake of tryptamine by intestinal brush-border membrane vesicles was examined. The uptake of tryptamine was inhibited by tetracaine and imipramine. The inhibitory effect of these cations was well correlated with changes in the membrane surface potential in the presence of tetracaine or imipramine. These results suggest that the K(+)-diffusion potential-dependent uptake of tryptamine by intestinal brush-border membrane vesicles is affected by membrane surface potential, and the inhibition of tryptamine uptake originates in changes in the membrane surface potential caused by the organic cations. PMID- 7880858 TI - Tetrapentylammonium (TPeA): slowly dissociating inhibitor of the renal peritubular organic cation transporter. AB - The efflux of tetraethylammonium (TEA) from suspensions of rabbit renal proximal tubules is completely blocked by 500 microM tetrapentylammonium (TPeA) in the extracellular medium. The basis of this trans-inhibition of TEA transport by TPeA was examined in tubule suspensions. At TPeA concentrations < 10 microM, efflux of TEA was reduced by approximately 50%, whereas at concentrations > 10 microM, TPeA reduced efflux an additional 50% to produce a near complete block of TEA efflux. Increasing concentrations of TPeA from 0-500 microM were found to produce a biphasic, concentration-dependent trans-inhibition of TEA efflux from tubule suspensions suggesting that TPeA may block efflux by binding to both a high and low affinity TPeA binding site. The trans-inhibition of TEA efflux by TPeA at low concentrations (< 10 microM) may result from a slow carrier turnover when TPeA is bound to the carrier site. To determine whether the inhibitory effectiveness of TPeA was also associated with its slow dissociation from the carrier site, the effect of a 10 s preincubation with 1 microM TPeA on TEA uptake was examined. The uptake of TEA by tubules preincubated for 10 s with TPeA was reduced by approximately 30-50% compared to control tubules not preincubated with TPeA. A 10 s preincubation with 150 microM unlabeled TEA had no effect on TEA uptake compared to control tubules not preincubated with TEA. When the 10 s preincubation with 1 microM TPeA was followed by a 10 min recovery period, TEA uptake returned to control levels, indicating that the prolonged inhibition was reversible. This prolonged inhibition of TEA uptake after a 10 s preincubation with 1 microM TPeA, as suspected, may arise from a slow dissociation of TPeA from the OC transporter following a rapid association to the binding site. TPeA inhibition of TEA uptake into tubules was competitive in nature with a Ki of 1 microM. The ability of TEA to compete with TPeA for binding to the carrier suggests that the binding of TPeA to the carrier can be displaced by large concentrations of TEA. These observations suggest that the interactions of TPeA, and perhaps similarly large hydrophobic OCs, with the OC transporter are complex. PMID- 7880859 TI - Active transport of ions across membranes: energetic role of electrostatics and binding site asymmetry. AB - The active transport of ions across a membrane by an ATP-driven electrogenic ion pump is often described by an 'alternate access' model. The position of the binding site is assumed to be unchanged as the binding cavity opens alternatively to the uptake and discharge sides of the membrane. The ion binding affinity is higher on the uptake side of the membrane than on the discharge side. This difference in affinities is related to the maximum transport rate and to the efficiency with which ATP hydrolysis is coupled to active transport. Here we examine the electrostatic contribution to binding affinities, using a simple geometry for a model membrane-protein system, a continuum dielectric approximation, and a numerical method to calculate binding energy as a function of the binding site location. If the binding site is located asymmetrically, being further from the uptake side of the membrane than from the discharge side, there is a significant difference in binding free energy between the uptake and discharge states. This asymmetry can produce differences in affinities that are consistent with those measured for biological active transport systems. These results may account for the observed asymmetric location of the calcium binding site in the calcium ATPases from sarcoplasmic reticulum and from the plasma membrane. Electrostatic energy differences associated with binding site asymmetry may be a general feature of electrogenic transmembrane ion pumps. PMID- 7880860 TI - Observation of extremely heterogeneous electroporative molecular uptake by Saccharomyces cerevisiae which changes with electric field pulse amplitude. AB - Molecular uptake of a charged fluorescent molecule (calcein; 623 Da, z = -4) was quantitatively determined at the single cell level using flow cytometry. Dilutely suspended cells were exposed to one exponential pulse (tau p approximately 300 microseconds) for different field strength values. For an asymmetric cell such as the yeast Saccharomyces cerevisiae a significant variation in the number of molecules taken up by individual cells was expected for physical reasons. By carrying out several thousand individual cell measurements for each pulse condition, we found that the number of molecules per cell varies significantly within the cell population, and that this population distribution changes markedly as the field strength is varied. Surprisingly, in spite of significant changes in this distribution with field strength, the average uptake per cell reaches a non-equilibrium plateau for which the uptake per cell is much smaller than the product of the mean cell volume and the supplied extracellular concentration. These observations of different field-dependent cell population distributions of uptake support the hypotheses that (1) electroporation is a transmembrane voltage-responsive phenomenon, so that cells of different sizes, shapes and orientation, respond differently to even a spatially uniform applied field, (2) population average measurements of electroporation behavior can be incomplete and misleading, and (3) transport of small charged molecules is due to electrophoresis through the pores of a dynamically changing pore population. PMID- 7880861 TI - Targetability of novel immunoliposomes modified with amphipathic poly(ethylene glycol)s conjugated at their distal terminals to monoclonal antibodies. AB - Distearoyl-N-(3-carboxypropionoyl poly(ethylene glycol) succinyl)phosphatidylethanolamine (DSPE-PEG-COOH) was newly synthesized and used to prepare novel immunoliposomes carrying monoclonal antibodies at the distal ends of the PEG chains (Type C). Liposomes were prepared from egg phosphatidylcholine (ePC) and cholesterol (CH) (2;1, m/m) containing 6 mol% of DSPE-PEG-COOH, and a monoclonal IgG antibody, 34A, which is highly specific to pulmonary endothelial cells, was conjugated to the carboxyl groups of DSPE-PEG COOH to give various amounts of antibody molecules per liposome. Other immunoliposomes with PEG coating (Type B) or without PEG coating (an earlier type of immunoliposome, Type A) were prepared for comparison. The average molecular weight of PEG in Type B or C immunoliposomes was 2000. Type B and Type C liposomes without antibodies showed prolonged circulation time and reduced reticulo-endothelial system (RES) uptake owing to the presence of PEG. These three different types of 34A-immunoliposomes with 30-35 antibody molecules per vesicle were injected into mice to test the immunotargetability to the lung. The efficiency of lung binding of 34A-Type B was one-half of that of 34A-Type A, though a large amount of 34A-Type B remained in the blood circulation for a long time, suggesting that the steric hindrance of PEG chains reduced not only the immunospecific antibody-antigen binding, but also the RES uptake. The degree of lung binding of 34A-Type C was about 1.3-fold higher than that of 34A-Type A, indicating that recognition by the antibodies attached to the PEG terminal was not sterically hindered and that the free PEG (i.e., that not carrying antibody) was effective in increasing the blood concentration of immunoliposomes by enabling them to evade RES uptake. The latter phenomenon was confirmed by using nonspecific antibody-Type C immunoliposomes (14-Type C), which showed a high blood level for a long time. Our approach provides a simple means of conjugating antibodies directly to the distal end of PEG which is already bound to the liposome membrane, and should contribute to the development of superior targetable drug delivery vehicles for use in diagnostics and therapy. PMID- 7880862 TI - Surface charge, fluidity, and calcium uptake by rat intestinal brush-border vesicles. AB - Biological membrane outer surfaces are negatively charged and interact with positively charged calcium ion during calcium uptake. Positively charged polycations such as polyarginine bind to membranes with high affinity, displacing bound calcium from the membrane. We tested the effect of polyarginine on uptake of calcium by brush-border membrane vesicles and examined the responses in terms of membrane fluidity by electron paramagnetic resonance (EPR). Polyarginine inhibited the saturable component of calcium uptake by a mechanism combining inhibition characteristics of strontium (competitive) and magnesium (non competitive). Unlike the inhibition of non-saturable calcium uptake by strontium and magnesium, polyarginine increased kD, the rate constant for non-saturable calcium uptake, by a concentration dependent mechanism. These effects of polyarginine on calcium uptake were associated with decreased membrane fluidity at the uptake temperature. These findings are consistent with a role for surface negative charge in determining both saturable and non-saturable calcium uptake. Increased membrane fluidity is associated with decreased saturable and increased non-saturable calcium uptake. Although increased fluidity might be involved in the increased kD for non-saturable uptake, the concentration-specific stimulating effect of polyarginine suggests a gating mechanism. PMID- 7880863 TI - New aspects of the interaction of cholesterol with dipalmitoylphosphatidylcholine bilayers as revealed by high-sensitivity differential scanning calorimetry. AB - We have investigated the effects of cholesterol on the thermotropic phase behavior of annealed and unannealed aqueous dispersions of dipalmitoylphosphatidylcholine (DPPC) using high-sensitivity differential scanning calorimetry (DSC), concentrating particularly on the cholesterol concentration range from 0 to 20 mol%. We find that the incorporation of cholesterol into low-temperature annealed DPPC bilayers decreases the enthalpy of the subtransition without affecting the transition temperature, such that the subtransition is abolished by 20 mol% cholesterol. Similarly, the incorporation of cholesterol progressively decreases the temperature and enthalpy of the pretransition and abolishes it entirely at cholesterol concentrations above 5 mol%. The incorporation of increasing quantities of cholesterol also alters the main or chain-melting phase transition. At cholesterol concentrations of 2 to 20 mol% cholesterol, the DSC endotherm arising from the main transition consists of superimposed sharp and broad components, the former due to the melting of cholesterol-poor and the latter to the melting of the cholesterol-rich DPPC domains. The temperature and cooperativity of the sharp component decreases slightly with increasing cholesterol concentration whereas the enthalpy decreases markedly, becoming zero at 20-25 mol% cholesterol. In contrast, the temperature and enthalpy of the broad component increases, and the cooperativity decreases markedly over this same range of cholesterol concentrations. An apparent increase in cooperativity of the overall DPPC endotherm at 7 mol% cholesterol is shown to arise because of a convergence in the transition temperatures of the sharp and broad components of the DSC endotherms. Some of our experimental findings, particularly the absence of any evidence for the existence of a triple point near 7.5 mol% cholesterol, do not accord with a recently proposed DPPC/cholesterol phase diagram derived from DSC and 2H-NMR data (see Vist, M.R. and Davis, J.H. (1990) Biochemistry 29, 451-464). In addition, we examined the effect of cholesterol on phosphatidylcholines (PCs) of different chain lengths and confirm that a eutectic point does not exist for any of these PC/cholesterol mixtures. We then propose a new, more complete DPPC/cholesterol phase diagram based on our high-sensitivity DSC data as well as some recent spectroscopic data on PC/cholesterol mixtures and explore some of its biological implications. PMID- 7880864 TI - Antioxidative activity of quercetin and quercetin monoglucosides in solution and phospholipid bilayers. AB - The antioxidative effect of quercetin, quercetin 3-O-beta-D-glucopyranoside (Q3G), quercetin 4'-O-beta-D-glucopyranoside (Q4'G) and quercetin 7-O-beta-D glucopyranoside (Q7G) was examined in solution and liposomal phospholipid suspension. First, their peroxyl radical-scavenging activities were investigated by measuring the inhibition of hydroperoxidation of methyl linoleate initiated by a radical initiator, 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN). Quercetin exhibited the highest peroxyl radical-scavenging activity judging from the rate of hydroperoxidation during the induction period (Rinh) and the length of induction period (tinh). Although Q7G showed an induction period, its Rinh was higher and its tinh was lower than that of quercetin. Neither Q3G nor Q4'G gave a clear induction period in the curve of hydroperoxide formation. The rate of hydroperoxidation in the presence of Q3G was higher than Rinh of quercetin and the oxidative loss of Q3G was much slower than quercetin or Q7G when exposed to AMVN in solution. Q4'G exerted little inhibition compared to Q3G or Q7G. Next, the antioxidative activity of quercetin and its monoglucosides in phospholipid bilayers was examined by measuring the inhibition of lipid peroxidation in large unilamellar vesicles composed of egg yolk phosphatidylcholine (PC) and a water soluble radical initiator. They retarded the accumulation of PC-hydroperoxides and the induction period increased in the order of Q4'G < Q3G approximately Q7G < quercetin. It is therefore concluded that quercetin acts as an antioxidant more efficiently than its monoglucosides when phospholipid bilayers are exposed to aqueous oxygen radicals. PMID- 7880865 TI - Restriction fragment length polymorphism of the major histocompatibility complex linked heat shock protein 70 (Hsp70) genes of the rat. AB - DNAs from inbred rat strains representing eighteen major histocompatibility complex (RT1) haplotypes have been tested for restriction fragment length polymorphisms of the three heat shock protein 70 (Hsp70) genes mapping into this complex. The DNAs were digested with restriction enzymes BamHI, EcoRI, PstI or PvuII and assayed by probes hybridizing to all three genes or selectively to Hsp70-1, Hsp70-2 and Hsp70-3, respectively. Three to four alleles were detected with each enzyme and in total five different strain distribution patterns could be found. Neither deletions nor amplifications of genes were detected in the three-gene Hsp70 cluster. PMID- 7880866 TI - Genetic characterization of the mouse strains of the Institute for Animal Breeding of the Veterinary Faculty of the University of Munich, Germany. AB - A total of 15 strains of mice (11 inbred lines, 4 outbred stocks) of the institute for animal breeding of the veterinary faculty of the university of Munich (FRG) were scored for 23 biochemical loci each. The allelic distribution and frequencies were recorded as a basis for a so far not established genetic monitoring system. The inbred strains revealed the expected homozygosity with one exception (strain UMDH/+; locus Es1). The outbred stocks showed a remarkable degree of variable loci (17.4-36.3%) with a mean heterozygosity between 0.05 and 0.12. The markers in use allow differentiation between all strains (except for one pair of sublines) and stocks. 14 of the loci show allelic differences among the strains and thus can be used for a genetic monitoring system. PMID- 7880868 TI - A surgical model for studying biliary excretion of drugs in the awake micropig yucatan. AB - The pig is probably one of the best mammalian models for studying the digestive functions and the biliary excretion of drugs because of the tight similarities with humans. Insertion of a T drain in the common bile duct after cholecystectomy in humans became uncommon because of surgical progress. For this reason, we developed a model using a bidirectional cannula to study the biliary secretion in the conscious Micropig Yucatan. We used this breed because of their ready availability and low stable weight. The surgical procedure was a double choledococholedocal fistula with a bypass on the main biliary duct, maintaining the continuous flow of bile into the duodenum through the sphincter of Oddi. This fistula remained effective for at least sixty days with normal hepatic biologic parameters. The development of our model could improve the biliary excretion study of drugs. Comparison of different routes of administration and interaction pharmacokinetic studies could also be studied in the same micropig, eliminating intersubject variations. PMID- 7880869 TI - The elderly patient with coronary heart disease: contemporary practices and future challenges. PMID- 7880867 TI - Time-related changes in functional activity of mouse spermatozoa during in vitro or in vivo incubation. AB - The kinetics of functional modifications during in vivo or in vitro incubation was studied in spermatozoa from Albino Swiss mice, obtained from cauda epididymis (E) or from uterus (U) or oviduct (O) post copulation (p.c.). Results clearly suggest that functional activity as reflected by measurements of motility, hypoosmotic swelling test and acrosome reaction differs according to the segments of the reproductive tract from which they were collected. The comparison of results obtained after equivalent periods of in vitro or in vivo incubation, shows that the time course of changes in sperm motility and percentage of swollen sperm is similar in both conditions. Since the percentage of acrosome-reacted gametes was higher in O, at all times scored, oviductal environment appeared to be capable of inducing this phenomenon. Our experimental conditions seemed to be adequate for completion of spermatozoa maturation and successful interaction between male and female gametes as reflected by the results of fertilization rate and embryo cleavage. PMID- 7880870 TI - Cardiovascular reserve capacity in healthy older humans. AB - In healthy normotensive individuals who have been rigorously screened to exclude coronary disease, the cardiovascular reserve capacity decreases with aging. A reduction in the maximum aerobic capacity is accompanied by a reduction in the maximum heart rate. Stroke volume during vigorous exercise in the upright position does not decline with aging in healthy individuals, because the left ventricular end-diastolic volume dilates more in older than in younger individuals; however, the reduction in left ventricular end-systolic volume that occurs during exercise is blunted in older individuals, resulting in a lesser increase in the left ventricular ejection fraction. This pattern of altered cardiac reserve resembles that caused by beta-adrenergic blockade, and substantial evidence indicates that the efficacy of the beta-adrenergic post synaptic response of cardiovascular tissues declines with aging. Changes in cardiac structure, e.g., enlargement of cardiac myocytes leading to a moderate heart wall thickening, and changes in vascular properties, e.g., aortic wall thickening and increased stiffness, also likely have a role in the reduction in left ventricular reserve in older individuals. Chronic exercise conditioning in older individuals increases aerobic capacity, decreases arterial stiffness and left ventricular function. The exercise heart rate deficit that occurs with aging, however, is not affected by physical conditioning. PMID- 7880871 TI - Surgical pathology of valve disease in the elderly. AB - Since age is no longer considered an additional risk factor for cardiac surgery, the epidemiology of valve disease in the elderly at present may be estimated from the surgical pathology evaluation of valve specimens which are resected at the time of valve replacement. In the time interval 1991-1993, 500 patients underwent native cardiac valve replacement or repair at our University, with a total of 549 valves available for gross and histological examination. Single valve surgery was performed in 451 patients (300 aortic, 148 mitral, 3 tricuspid), and double valve replacement in 49 (47 mitral-aortic, 1 aorto-tricuspid and 1 mitral-tricuspid). Two hundred and eighteen patients (44%) were older than 65 years; the mean age was 70.4 +/- 4.3 years, and the male to female ratio was 0.9 to 1. Two-thirds of the interventions in the elderly group were aortic operations. However, regardless of the age group, 50 and 60% of the cases with respectively aortic and mitral valve disease were due to rheumatic disease. Age-related degenerative valve diseases were prominent; senile dystrophic calcification with aortic stenosis mostly in the elderly, anuloaortic ectasia with aortic incompetence mostly in adults, and floppy valve with mitral incompetence in both age groups. Bicuspid aortic valve, a congenital anomaly which is silent until adulthood, accounted for both aortic stenosis and stenoincompetence by dystrophic calcification, and pure aortic incompetence by endocarditis or anuloaortic ectasia. Our findings suggest that although age-related degenerative valve diseases are increasing, rheumatic disease still remains the leading cause of valve dysfunction in our country even in the elderly. These data may have an impact on prevention strategies and health-care costs. However, it has to be pointed out that the high prevalence of rheumatic disease is a feature of this particular study but is different from the findings of other studies around the world. PMID- 7880872 TI - Aging enhances serotonergic cardiovascular blockade by ketanserin in conscious rats. AB - We recorded cardiovascular responses to serotonin (5-HT) and to two selective serotonergic agonists following ketanserin treatment in 3 groups of conscious rats aged 4, 14 or 24 months. The selective agonists were DOI (5-HT2 agonist), and phenylbiguanide (5-HT3 agonist). Before ketanserin treatment, pressor responses to 5-HT or DOI were larger while reflex bradycardic responses to 5-HT or phenylbiguanide were smaller in 14- and 24-month than in 4-month-old rats. Ketanserin treatment lowered blood pressure consistently, and the ensuing hypotension was more pronounced in 14- and 24-month than in 4-month-old rats. Pressor responses to DOI were attenuated similarly in all rats, but those to 5-HT were reversed to depressor responses whose magnitude was smaller in 14- and 24 month than in 4-month-old rats. On the other hand, bradycardic responses to 5-HT and phenylbiguanide were enhanced in 14- and 24- but not in 4-month-old rats. Our results indicate that even before ketanserin was given, old rats had enhanced pressor responses to 5-HT2 agonists together with weakened bradycardic responses to 5-HT3 agonists. Following ketanserin treatment, 5-HT2 pressor responses were blocked while 5-HT3 bradycardic responses were enhanced but only in old rats. These results are compatible with the interpretation that the more pronounced hypotension produced in old rats by ketanserin is due to two complementary effects on serotonergic receptors: blockade of 5-HT2 pressor responses coupled with selective enhancement of 5-HT3 bradycardic responses. PMID- 7880873 TI - Hypertension in the elderly population: prevalence data from an urban area in Sweden. AB - Data from the total urban elderly population (75 years and older) in Kungsholmen, Stockholm, were used to calculate age- and sex-specific prevalence of hypertension. Blood pressure was measured as part of the examination in the population survey (the Kungsholmen Project). The blood pressure of 1751 elderly people and any antihypertensive treatment were recorded. The prevalence of hypertension was 54 and 59 per 100 population for men and women, respectively. No great variation was observed with age or sex. Isolated systolic hypertension was most frequent with increasing prevalence in advanced ages, while isolated diastolic hypertension and systolic and diastolic hypertension showed a tendency of decreased prevalence with age. In the subjects studied, 18% were being treated for hypertension. Hypertension was detected in 47% of those not undergoing treatment. Among those, 76% had high blood pressure measurements. Our data demonstrate that hypertension is a prevalent disease in the very old, in both sexes, and support the need for hypertension screening programs as well as programs to evaluate the efficacy and benefits of treatment in this age group. PMID- 7880874 TI - Effect of body fat on exercise hemodynamics in sedentary older men. AB - Morbid obesity is often associated with cardiac dilatation and left ventricular dysfunction. The present study investigated whether a similar relationship exists between mild and moderate obesity and left ventricular reserve function in 28 middle aged and older men (58.6 +/- 6.1 years, mean +/- SD). Subjects had a body mass index of 26.4 +/- 2.9 kg/m2, a percent body fat determined by hydrodensitometry ranging from 9.5% to 33.8%, and were carefully screened to exclude cardiovascular disease. Left ventricular function was assessed by gated blood pool scans at rest and during exhaustive upright cycle exercise. There were no significant relationships between resting or exercise cardiac volumes or ejection fraction with percent body fat; however, peak work rate/kg correlated inversely with percent body fat (r = -0.68, p < 0.0001). Heart rate reserve, defined as heart rate at peak work rate minus resting heart rate, declined significantly with increasing percent body fat (r = -0.47, p = 0.01). End diastolic volume index reserve also tended to decline with increasing percent body fat, but stroke volume index and cardiac index reserve were maintained because the decrease in end systolic volume index from rest to maximal exercise was greatest in those subjects with highest percent body fat (r = -0.41, p = 0.03). Therefore, rest and exercise left ventricular function are not related to percent body fat in healthy older men. However, older more obese men have a smaller increase in heart rate and end diastolic volume and a greater decrease in end systolic volume from rest to peak effort as a mechanism to augment exercise cardiac output. PMID- 7880875 TI - The cardiopulmonary response to incremental exercise test: the effect of aging. AB - The aims of the present study were to define the respective roles of the cardiac and respiratory response to exercise as determinants of the age-related physiological decrease in exercise performance, and to assess the relationship between aging and interindividual variability in the response to effort. We studied 91 normal subjects recruited in three age-groups: Group A (42 children, aged 10 +/- 2 years); Group B (29 young adults, aged 27 +/- 5 years); Group C (20 elderly, aged 74 +/- 9 years). All the subjects underwent an incremental cycle ergometer exercise test with a work load increase of 15 W every 2 minutes in groups A and C, and 25 W every 2 minutes in group B, until they achieved 80% of the predicted maximal heart rate. Ventilatory equivalent changes during exercise were significantly lower in group A than in the other two groups, and in group B compared to group C. Exercise-induced changes in oxygen pulse were significantly higher in group A, but no difference was found between groups B and C. Thus, gas exchange function and overall exercise performance decrease with advancing age, whereas cardiovascular performance is well maintained in normal elderly subjects. Discriminant analysis showed that the exercise response conformed to the group specific model in 74% and 79% of subjects in groups A and B, but only in 50% of the group C subjects; 5% and 45% of the elderly subjects were functionally classified in groups A and B, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880876 TI - Vascular responses to neuropeptide Y in the rat: effect of age. AB - Neuropeptide Y (NPY) is co-released with norepinephrine (NE) from sympathetic neurons, which innervate blood vessels, and acts to potentiate NE-induced smooth muscle contraction. This study sought to determine if vascular levels of NPY-like immunoreactivity or the contractile effects of NPY are altered by age in segments of isolated blood vessels from Fischer 344 and Brown Norway-F344-F-1 rats. Tissue extracts of femoral and tail arteries of Fischer 344 rats, aged 6, 12, 20, and 24 months, were analyzed for NPY content by radioimmunoassay. Neither blood vessel showed a significant age-related difference in NPY content. Contractile responses of the tail artery to adrenergic transmural nerve stimulation (TNS) were compared in the same age groups. No significant age-related differences in contractile responses to TNS were observed in either rat strain. NPY, at concentrations of 1 and 10 nM, both potentiated and prolonged the contractile response to TNS; 6 month-old F-344 rats were significantly less responsive to the effects of NPY. However, advancing age from 12 to 24 months did not alter the responses to NPY in either rat strain. We conclude that an age-dependent increase in the contractile responses to NPY occurs from age 6 to 12 months, and this responsiveness to NPY is maintained through senescence. PMID- 7880877 TI - Longitudinal study of the hematocrit of ad libitum fed and dietary restricted male F344 rats. AB - A longitudinal study of age-change in the hematocrit (Hct) was conducted with ad libitum fed and dietary restricted male F344 rats. A progressive fall in Hct occurred over the age range of 3 to 20 months. The magnitude of this decrease in Hct was similar in ad libitum fed and dietary restricted rats. Whether this age associated decline in Hct continues after 20 months of age cannot be answered with certainty because of the occurrence of diseases at advanced ages which can mask or exacerbate the effects of the aging processes on the Hct. Studies of similar design with males and females of other strains of rats are needed to establish that a decreasing Hct is characteristic of aging in this species. PMID- 7880879 TI - Characterization of biomolecules by electrophoretic analysis of reversible interactions. PMID- 7880878 TI - Effect of age on renal blood flow during exercise. AB - The present study examined the effect of age on the control of renal blood flow (RBF; PAH clearance) and renal vascular conductance (RVC = RBF/mean arterial pressure) during and after a bout of dynamic exercise in a warm environment. Six healthy fit older men (O; 67 +/- 1 years) and 6 young men (Y; 24 +/- 2 years) were matched for body size, adiposity, and maximal oxygen uptake (VO2max). Subjects exercised at approximately 50% of VO2max for 90 minutes in an environment of 30 degrees C, 60% humidity on each of 4 consecutive days, with data collected on days 1 and 4. There was no effect of repeated days of exercise on RBF or RVC, despite a 4% expansion of blood volume in Y (< 1% in O). On each day, resting RBF was significantly lower in O (e.g., Y = 1127 +/- 67, O = 852 +/- 114 mL/min on day 1; p < 0.05). During exercise, Y decreased RBF to a significantly (p < 0.05) greater extent [-508 (-45%) and -365 (-36%) mL/min on days 1 and 4, respectively] than the O [-98 (-12%) and -83 (-12%) mL/min]. RVC followed a similar pattern, decreasing by 52% and 37% during exercise for Y vs only 15% and 13% for O. The relationships between delta RBF and HR and delta RBF and plasma norepinephrine concentration were independent of age, implying similar sympathetic control during exercise. During recovery, RBF and RVC increased as expected in Y, but continued to decrease in O, falling significantly below exercise values (p < 0.05). Compared to young men, fit healthy older men redistribute less blood flow away from the kidneys during dynamic exercise in the heat, an effect which appears to result from the existence of a smaller resting RBF rather than differential sympathetic control. On the other hand, chronological age seems to be associated with altered control of RBF and RVC during recovery from exercise. PMID- 7880881 TI - The biased reptation model of DNA gel electrophoresis: a user guide for constant field mobilities. AB - The biased reptation model of DNA gel electrophoresis is simple enough to allow one to obtain detailed analytical and numerical predictions for experimentally relevant situations. Although it is not always applicable for explaining experimental results, the biased reptation model is usually a good starting point for data analysis. Unfortunately, the model is often reported as being incapable of explaining experimental data because the users have not analyzed the data properly or because they attempted to use the model outside its expected range of applicability. This article presents a detailed practical guide to the model and its limitations, as well as a complete description of its predictions regarding the analysis of constant field mobilities. PMID- 7880880 TI - Electrophoretic free mobility and viability of microbial cells: a preliminary study in preparation for space experiments. AB - Electrophoretic free mobilities (EFM) of four fungal spores and five bacterial cells were determined in 7 mM triethanolamine/acetate (TEA) buffer by means of microscopic electrophoresis (ME) and free flow electrophoresis (FFE). Spores of Aspergillus terreus, Penicillium citrinum, Gliocladium virens, and Rhizopus oryzae had similar EFM from 2.2 to 3.1 microns sec-1/V cm-1. The resolution of the spore mixture by FFE was therefore determined to be poor. Bacterial cells of Salmonella typhimurium LT2 mutants showed a distinctive EFM from 0 to 4.2 microns sec-1/V cm-1, which is a large enough difference to produce a clear separation of each mutant type from the mixture in FFE. The differences in the EFM of bacteria result from defective structures in the lipopolysaccharide of their outer membranes. The viability of bacteria in TEA buffer at 4 degrees C was investigated, and it was found to be stable for 14 days. This period is long enough to allow the performance of space experiments. PMID- 7880882 TI - Charge modification in rodent hepatic Grp78/BiP following exposure to structurally diverse peroxisome proliferators. AB - This investigation was conducted to determine the comparative effect of structurally diverse peroxisome proliferators (PP) on the two-dimensional protein pattern of rat liver whole homogenates. Perfluoro-n-decanoic acid (PFDA), perfluoro-n-octanoic acid (PFOA), clofibrate, and di(2-ethylhexyl)phthalate(DEHP) are all known to cause the proliferation of hepatic peroxisomes and the induction of peroxisomal beta-oxidative and microsomal omega-oxidative enzymes. To detect potential differences between these compounds with regard to the liver, we examined the unique patterns of protein alteration produced by in vivo exposure to them. Following exposure to various doses, whole liver homogenates were prepared and separated by two-dimensional gel electrophoresis (2DE) using the ISO DALT System. Stained gels were digitized and protein patterns analyzed using the Kepler 2D Gel Analysis System. Immunoglobulin heavy-chain binding protein (BiP), also known as 78 kD glucose regulated protein (Grp78), was identified immunologically and by comigration of recombinant Grp78. BiP is a luminal endoplasmic reticular (ER) protein that functions in the assembly and folding of nascent proteins as they enter the ER. The present results suggest a selective posttranslational modification of BiP following PFDA exposure. Single-dose exposure to PFDA was associated with a notable charge-modification of BiP that persists up to 30 days. PFOA, clofibrate, and DEHP had less effect in this regard. Our data suggest the likely nature of this PFDA-associated protein modification is associated with protein-phosphorylation. These results document the unique nature of PFDA's hepatotoxicity with respect to classic peroxisome proliferators and support the utility of 2D gel analysis in toxicity testing. PMID- 7880883 TI - Mouse cells with null p53 mutation have all p53 isoforms deleted and lose negative growth control. AB - Embryonic mouse cells containing a disrupted p53 gene (-/-) were compared to the heterozygote (+/-) and homozygote control (+/+) for growth characteristics and the presence of p53 protein isoforms. There were considerable morphological differences between the null cells and homozygote, with the null cells having irregular shapes and sizes, and densely staining pleomorphic nuclei. Growth curves showed the null cells to have essentially remained in log phase growth during the course of these studies, losing contact inhibition. Losses of all protein isoforms indicate a single locus origination, and suggest that the multiple protein isoforms observed are due to different net charges on the protein as a result of post-translational modification. These results confirm deactivation of the p53 gene by site-specific disruption of exon 5 as described by Donehower (Donehower et al., 1992). PMID- 7880884 TI - High resolution 2-D peptide mapping with subsequent analysis of peptides by microsequencing or lectin binding directly from PVDF membrane blots. AB - Peptide mapping is a technique that is frequently used to characterize proteins. Typically, the method involves the cleavage of proteins in solution or in a gel with the subsequent separation of the peptide fragments on a 1-D SDS PAGE gel. Electrophoretic peptide maps are often used to compare homologous proteins from related organisms to derive evolutionary relationships. Other applications of peptide mapping include immunoblotting studies of selected proteins. Two dimensional peptide mapping, a less common technique, has traditionally involved a combination of thin layer or paper chromatography and electrophoresis. Amino acid sequencing of peptides that were separated using this method and then subsequently blotted to PVDF membrane was reported recently. However, the resolution achieved with these methods is far below that which can be achieved with conventional 2-D electrophoresis of proteins in polyacrylamide gels. This report describes an electrophoretic system for the high resolution 2-D separation of peptides in gels with subsequent blotting to a novel cationic PVDF membrane, Immobilon-CD, and microsequencing directly from the 2-D blot. In addition, the high resolution peptide maps can be further analyzed by techniques such as lectin probing to determine post-translational modifications. PMID- 7880885 TI - Immunoreactivity of cytochrome c: antibodies to horse cytochrome c distinguish between sequence-related cytochromes only at the level of the 3-D-structure. AB - It has long been known that antibodies to cytochrome c can distinguish between closely sequence-related cytochromes c. Because the 3-D-structure of the polypeptide chain is virtually identical among eukaryotic cytochromes c, antibody specificity is directed against amino acid substitutions within a common polypeptide folding pattern. The question arises if the specificity is observed at the level of the 3-D-structure (conformational epitopes) and/or at the level of the primary structure (sequential epitopes). Using rabbit sera to horse cytochrome c, we show that discrimination against the host's own cytochrome c (six amino acid changes) occurs exclusively at the 3-D-level and not between peptides with sequences typical for horse and rabbit cytochrome c. Furthermore, deliberate immunization with horse apo-cytochrome c produces antibodies that cannot discriminate efficiently between sequence-related apo-cytochromes c. B cell tolerance to the host's own protein seems to be restricted to the intact, native cytochrome. These findings bear on the application of antisera to distinguish between closely related proteins. PMID- 7880886 TI - The protein moiety modulates the redox potential in cytochromes c. AB - Cytochrome c is one of the most thoroughly documented oxidoreduction proteins. Its electron transfer activity, which involves an association between the heme group and the polypeptidic chain, is correlated with the redox potential value of the heme group. The redox potential covers a wide range up to 0.8 V, an extreme case being observed in the low-potential cytochromes c from sulfate reducing bacteria. On of the main roles of the polypeptidic moiety consists of modulating the redox potential value of the heme group. In this paper, some structural factors that seem likely to be involved in maintaining the redox potential value are described. PMID- 7880887 TI - Protein interaction sites obtained via sequence homology. The site of complexation of electron transfer partners of cytochrome c revealed by mapping amino acid substitutions onto three-dimensional protein surfaces. AB - Amino acid substitutions in all but the most divergent of cytochromes c have been categorized as being conservative or radical and mapped onto the three dimensional structure of yeast cytochrome c. Color-coded, space-filling representations reveal a large 24 A diameter surface area which is invariant or conservatively substituted on the front left face of the cytochrome c molecule. Chemical modifications and mutations which inhibit complex formation and electron transfer with reaction partners also map to this surface. In sharp contrast, the back side of the protein is randomly substituted with both conservative and radical replacements. The invariant/conservatively substituted surface on the front of cytochrome c thus defines the site of interaction with redox partners and provides a measure of its dimensions. Further, this analysis strongly suggests that there is only a single site of oxidation and reduction on cytochrome c for all of its physiological reactions. The same analysis applied to bacterial cytochrome c2 shows that its conserved surface is similar in size and location to that of cytochrome c. Analyses of native and model reaction partners of cytochromes c and c2, such as cytochrome b5, plastocyanin, and bacterial photosynthetic reaction centers, also reveal probable active site surfaces for complexation and electron transfer, which are complementary in size to that of the c-type cytochromes. The availability of a three-dimensional structure and of several closely related amino acid sequences for a given functional class of protein is the only limitation on this type of analysis, which can then serve as a basis for designing site-directed mutagenesis experiments. PMID- 7880888 TI - The interaction of horse heart cytochrome c with phospholipid bilayers. Structural and dynamic effects. AB - The interaction of cytochrome c with phospholipid bilayers is reviewed. Special emphasis is given to the structural and dynamic perturbations induced, either in the membrane lipid component or protein itself, by the lipid-protein interaction. The lipid-induced perturbations in the structure of cytochrome c involve: i) conformational changes in and around the heme crevice, converting the heme iron to a high-spin state: and ii) a destabilisation/loosening of the overall tertiary and secondary structure. This highly mobile, partially unfolded intermediate of cytochrome c has a remarkable resemblance to partially folded membrane-bound intermediates of the precursor protein. The functional implications of lipid protein intermediates for (apo) cytochrome c in (protein-translocation) electron transfer are discussed. PMID- 7880889 TI - Structural studies on recombinant and point mutants of flavocytochrome b2. AB - Flavocytochrome b2 from S cerevisiae is a homotetramer with a molecular mass of 4 x 58 kDa. It catalyses the oxidation of L-lactate into pyruvate and the electron transfer to cytochrome c in the mitochondrial intermembrane space. Each monomer is composed of a flavinmononucleotide (FMN) carrying domain and a 'b5-like' heme domain. The wild type structure has been described at a resolution of 2.4 A. We report here on the refined structure of the E. coli native recombinant flavocytochrome b2 from S cerevisiae inhibited by sulphite and that of two point mutants, Y143F and Y254F, in which pyruvate is bound to the active site. The crystals, obtained under very different conditions from those of the native enzyme, are isostructural (P 3(2) 2 1, a=b=164.5 A, c=114.0 A). In line with the similarities found to exist in the kinetic behaviour of the native and recombinant protein, few structural differences were observed here, and the crystallographic data further confirm the intrinsic mobility of the heme domain. The superimposable position of the aromatic rings of Phe 143 in the mutant Y143F and Tyr 143 in the native protein makes it seem unlikely that the aromatic ring may be directly involved in the intramolecular electron transfer. The fact that a very restricted number of domain interactions was observed in Y143F shows that Tyr 143 is one of the amino acids essential to the formation of the productive complex. In the Y143F mutant, the number of catalytically efficient complexes is probably drastically decreased, which will severely limit the rate of intramolecular election transfer. The structure of Y254F shows a reorientation of the substrate at the active site. Together with the kinetic results, this finding definitely excludes the possibility that Tyr 254 may act as general base and that the substrate may interact directly with Phe 254 in the mutant. The model between flavocytochrome b2 and cytochrome c will serve as a basis for designing suitable mutants of the amino acids involved either in the interaction or the electron transfer. PMID- 7880890 TI - Involvement of electrostatic interactions in cytochrome c complex formations. AB - Structural studies on various electron transfer complexes involving the tetrahemic cytochrome c3 provided evidence that one of the hemes (heme 4) is the interacting site on the molecule. The reactivity of this particular heme is allocated to the positive charges found around the heme group which are strongly involved in the electrostatic interaction processes. Electrostatic and hydrophobic effects in complex formation are considered on the basis of two electron transfer complex examples: the soluble cytochrome c-cytochrome c peroxidase and the membrane bound photosynthetic reaction center. PMID- 7880891 TI - Individual redox characteristics and kinetic properties of the hemes in cytochromes c3: new methods of investigation. AB - The elucidation of the role of the four hemes in cytochromes c3 requires several complementary approaches. The measurements and the assignment of the redox potentials resort to magnetic spectroscopies, EPR and NMR, which are able to discriminate the hemes. The origin of the differences between the redox properties of the hemes can be studied by comparing their thermodynamic parameters delta S and delta H, as measured by the temperature dependence of their individual potentials. Lastly, the available data concerning the electron exchange between cytochromes c3 and their redox partners can be analysed through a detailed kinetic model which provides important information on the role of the different hemes. PMID- 7880892 TI - A detailed comparison of the refined structures of cytochrome c3 molecules from two strains in Desulfovibrio vulgaris: the relationship between the heme structures and their redox properties. AB - The refined structures of the cytochrome c3 molecules from Desulfovibrio vulgaris Miyazaki and Hildenborough have been compared in detail. Though there are no significant differences of the overall structure and spatial arrangement of four heme groups between two molecules, there are some unique features with regard to the local structures near the heme pockets. Two of the heme groups show significant differences including a hydrogen bonding scheme between the imidazole rings and water molecules in heme pocket. The water molecule near the heme 1 pocket in Miyazaki cytochrome c3 is replaced by the C delta 1 atom of Leu9 in the Hildenborough structure. The rotation around the C alpha-C beta bond of Leu9 results in the increase of the solvent accessibility of the portion of the heme 1 edge. On the other hand, in heme3 one water molecule is additionally included in the hydrogen bonding network with a N delta 1 atom of the imidazole ring and carbonyl oxygen atom of the main chain in Hildenborough cytochrome c3. This additional hydrogen bonding network will contribute to the possible passage between the imidazole ring and the molecular surface. These features have been related to the upfield shift of the C2 proton signals of NMR spectra and the low redox potentials of the cytochrome c3 molecules of Desulfovibrio vulgaris Hildenborough in comparison with those from Miyazaki. PMID- 7880893 TI - Molecular and structural basis of electron transfer in tetra- and octa-heme cytochromes. AB - The first three-dimensional structure of a dimeric, octa-heme cytochrome c3 (M(r) 26000) from Desulfovibrio desulfuricans Norway, established at 2.2 A resolution, is briefly presented and compared to the known 3-D-structures of different C3 type tetraheme cytochromes, in order to contribute to a better understanding of the function of multiheme clusters and of the role of conserved amino acids implicated in possible electron transfer pathways. The dimeric protein crystallizes in the space group P3(1)21 with a = 73.01 A, c = 61.81 A and the asymmetric unit contains one monomer subunit, the dimer being generated by the crystallographic two-fold axis. The 3-D-structure was solved using the molecular replacement method with a model based on the structure of the tetraheme cytochrome c3 (M(r) 13000) from D desulfuricans Norway, presently refined at 1.7 A resolution. The monomeric subunit has the same overall fold as all cytochromes c3 (M(r) 13000). Moreover, the heme core of all examined cytochromes c3 is highly conserved, but differences appear concerning the heme environments and the histidines, axial ligands of the heme-iron atoms. PMID- 7880894 TI - Molecular biology of c-type cytochromes from Desulfovibrio vulgaris Hildenborough. AB - Sulfate reducing bacteria of the genus Desulfovibrio harbor a wide variety of redox proteins. Three different c-type cytochromes, cytochrome c-553, cytochrome c3 and the high molecular mass cytochrome have been isolated from these bacteria. The high molecular mass cytochrome is part of an operon that encodes a transmembrane protein complex that mediates electron transfer across the cytoplasmic membrane. The physiological function of the other two cytochromes is less clear. They are encoded by monocistronic genes and their redox partners can thus not be identified by gene sequencing. Expression of genes for c-type cytochromes in a foreign host are complicated due to the requirement for covalent heme insertion. Cytochrome c-553 is readily expressed in Escherichia coli in functional form, but cytochrome c3 and the high molecular mass cytochrome are for reasons that are presently not clear. PMID- 7880895 TI - Recent advances in the characterization of the hexadecahemic cytochrome c from Desulfovibrio. AB - The biochemical characterization of the high molecular mass cytochromes c (Hmc) isolated from Desulfovibrio vulgaris has led to some controversy as regards their molecular size and subunit structure as well as their heme content and redox properties. Recently developed genetic techniques have made it possible to reach some definite conclusions about the structural and functional properties of the cytochrome. The hexadecahemic Hmc comprises four domains which resemble the tetrahemic cytochrome c3: the structure-function relationship between these multihemic proteins is examined. An hypothesis is discussed according to which the Hmc might be a peripherally interacting protein associated with the outer face of the cytoplasmic membrane, where it might interact with periplasmic proteins - [Fe] hydrogenase - and membrane-bound components of the hmc operon. PMID- 7880896 TI - Interaction between cytochrome c and the photosynthetic reaction center of purple bacteria: behaviour at low temperature. AB - In purple photosynthetic bacteria the electron donor to the special pair, after its oxidation by a light-induced reaction, is a c-type cytochrome: either a soluble monoheme cytochrome which forms a transitory complex with the reaction center, or a tetraheme cytochrome which remains permanently bound to the reaction center. The effects of low temperatures on electron transfer in the complex are presented and discussed. They provide estimates for the reorganization energy. The most prominent effect of low temperature is that a dominant fast phase of electron transfer becomes impossible at a temperature of around 250 K (monoheme cytochrome) or located between 250 K and 80 K according to the redox state (tetraheme cytochrome). This inhibition is attributed to a freezing-like transition of pools of water molecules which blocks structural changes of the protein which are normally associated with the cytochrome oxidation. PMID- 7880897 TI - Determinants of translational fidelity and efficiency in vertebrate mRNAs. PMID- 7880898 TI - Eukaryotic protein synthesis: an in vitro analysis. AB - The general mechanism of eukaryotic protein synthesis is discussed based upon the accumulation of considerable data from in vitro assays of either purified factors or reconstituted systems. Recent evidence suggests that there are more factors/proteins that participate in this process than previously thought. These new discoveries however, do not alter the apparent function of the previously characterized factors, so that the general guidelines for understanding how Met tRNA(i) and mRNA are correctly positioned on the 40S subunit have not changed. The two 'new' observations are the ability of a 67 kDa protein to influence the phosphorylation state of eIF-2 alpha and a new mechanistic interpretation of the utilization of the mRNA specific factors (eIF-4A, eIF-4B, eIF-4F) which would suggest that eIF-4A may not bind to mRNA except as a subunit of eIF-4F. PMID- 7880899 TI - Participation of initiation factors in the recruitment of mRNA to ribosomes. AB - The step of protein synthesis which is normally rate limiting, formation of the 48S initiation complex, is catalyzed by the group 4 initiation factors. Collectively they recognize the 7-methylguanosine-containing cap of mRNA, unwind mRNA secondary structure, and allow scanning for the initiation codon by the small ribosomal subunit. The activities of the eIF-4 polypeptides are modulated by phosphorylation. Recent studies shed new light on the mechanism of assembly of the 48S initiation complex and the effect of phosphorylation of one of the eIF-4 polypeptides, the cap-binding protein eIF-4E. PMID- 7880900 TI - Regulation of translation and cell growth by eIF-4E. AB - This review discusses the regulation of a key controlling step in the initiation of protein synthesis, the binding of mRNA to ribosomes. Particular focus is given to the phosphorylation of the cap-binding factor, eIF-4E, and the role of this factor in the regulation of cell growth. PMID- 7880901 TI - Expression of initiation factor genes in mammalian cells. AB - This review focuses on how cells establish the levels of initiation factors, within the broader context of determining levels of the translational machinery. Most initiation factor polypeptides are moderately abundant proteins with concentrations approaching those of ribosomes. eIF4A and eIF5A are more abundant than ribosomes, whereas eIF4F alpha and eIF2B are considerably less abundant than the other factors. The cloning of cDNAs generates hybridization probes for monitoring the levels and activities of factor mRNAs, and the cloning of their genes is just beginning to provide insight into promoter structures and regulation. Initiation factor gene expression appears to be coordinately regulated in many cases, and preferential synthesis is seen in mitogen-activated T-cells. The gene for eIF2 alpha has been best characterized, and mechanisms that provide for the coordinated synthesis of eIF2 subunits are emerging. Recombinant DNA methods also allow investigators to manipulate the levels of expression of specific factor genes by overexpression or antisense repression. Such approaches provide a means to investigate in vivo the mechanisms of action of the initiation factors and their roles in regulating translation rates. PMID- 7880902 TI - The yeast Saccharomyces cerevisiae system: a powerful tool to study the mechanism of protein synthesis initiation in eukaryotes. AB - This review summarizes recent progress in the study of initiation of protein synthesis in the yeast Saccharomyces cerevisiae. Biochemical and genetic approaches provide new insight into the recognition of the 5'-end of mRNA by initiation factors and 40S ribosomes, unwinding of mRNA secondary structures in the untranslated region and proper recognition of the AUG start codon. Experiments with initiation factor-dependent cell-free systems have facilitated studies of factor functions and factor requirements for translation of different mRNAs. The analysis of mutations which suppress the inhibitory effect on translation of RNA secondary structure in the 5'-untranslated region of yeast mRNAs has led to the identification of gene products which may be involved in both transcription and translation. PMID- 7880903 TI - Translational control of cytokine expression by 3' UA-rich sequences. AB - Several messenger RNAs which are transiently expressed contain a conserved uridine-adenosine-rich sequence in their 3' untranslated region. Many of these mRNas encode cytokines, growth factors or oncoproteins. This UA-rich sequence is composed of several interpsersed repeats of the octanucleotide UUAUUUAU and plays a key role in the post-transcriptional regulation of these mRNAs. Known as instability determinants, these UA-rich elements can also strongly affect mRNA translational efficiency. In this report, we review the data which illustrate this translational regulation and give insight the underlying mechanism. PMID- 7880904 TI - Regulation of translation by specific protein/mRNA interactions. AB - This review will focus on cases of specific translational control by protein/RNA interactions in the 5'- or 3'-UTR of eukaryote mRNA where either the cis-acting RNA determinant or the trans-acting protein (or preferably both) have been identified with fair certainty. Examples of messages that are regulated by 5' motifs, which are proposed to occlude ribosome binding when bound by their specific factors, include ferritin and ribosomal protein mRNAs and the autoregulated thymidylate synthase and poly(A)-binding mRNAs. However, it has become increasingly evident recently that 3' UTR determinants and their specific binding proteins also regulate translation efficiency either directly, or indirectly via an influence on the polyadenylation status of the mRNA. It is still unclear how events at the 3' end of mRNA influence ribosome binding. Most, if not all, of the mRNAs known to be regulated by 3' UTR motifs are subject to regulation during early development or during differentiation such as several spermatocyte and oocyte mRNAs and erythroid lipoxygenase mRNA. To date, in all cases where translation is controlled directly by specific protein/mRNA interactions, the protein seems to act as a negative regulator, a translational repressor, whose binding to the specific site on the mRNA results in inhibition of initiation. The only cases of translational activation known so far concern internal initiation of translation of picornaviral RNAs, but this topic is beyond the scope of this review. PMID- 7880905 TI - Regulation and function of non-AUG-initiated proto-oncogenes. AB - A small, yet growing, number of cellular eukaryotic mRNAs encoding important regulatory proteins, such as c-myc and other proto-oncogenes, initiate translation from a non-AUG codon, usually in addition to initiating at a downstream AUG. The efficiency of non-AUG initiation on these natural cellular mRNAs varies considerably and appears to be governed by several features, including the codon sequence, the context surrounding the codon and the secondary structure of the transcript. In addition to factors which control the overall efficiency of c-myc non-AUG initiation, the relative efficiency of the upstream non-AUG initiation compared with the AUG initiation changes during the growth of cells. As lymphoid and fibroblast cells approach high densities in culture there is a sustained 5-10-fold induction in the synthesis of the non-AUG-initiated c Myc 1 protein to levels comparable to or greater than the AUG-initiated c-Myc 2 protein. This increased efficiency of c-myc non-AUG initiation, due to methionine depletion of the growth medium, suggests that the scanning preinitiation complex can be regulated to enhance the recognition of a suboptimal non-AUG codon. The significance of non-AUG initiation for the growth-regulatory genes is illustrated by the different localizations of the int-2, bFGF and hck non-AUG-initiated proteins, the disruption of the c-myc and lyl-1 non-AUG initiation in tumor derived cell lines, and the distinct biological function of the non-AUG-initiated forms of bFGF. PMID- 7880906 TI - Into and out of G1: the control of cell proliferation. AB - Progression of cells through G1 is an orderly process which is regulated by a series of key proteins. Over the past few years a number of these proteins have been identified and their mode of action has been studied in detail. This review will concentrate on the current knowledge about the function in G1 of cyclins, cyclin dependent kinases, the retinoblastoma protein and other related 'pocket' proteins. Mutations or deregulation of some of these proteins confer a growth advantage and their role in malignant transformation will be discussed. PMID- 7880907 TI - Twenty-five years of progress: twenty-five more? AB - This address outlines important steps for ensuring the future of biofeedback and applied psychophysiology. These steps are contained in the acronym PHUTRE, wherein PH stands for Political activism of the Hard and fast variety, U represents United front, T encompasses Transfer of knowledge (from clinician to researcher, researcher to clinician, and from both to students in training), R refers to our Research base, and E represents the Excitement that our field has the potential to generate. PMID- 7880908 TI - Age and gender differences in the relationship between heart rate reactivity and elevated serum lipids. AB - Data on serum lipids and heart rate reactivity to a standardized mental arithmetic stressor were collected on 54 healthy men and 73 healthy women. Subjects' ages ranged from 18 to 61 years, allowing analysis of data from both young and older subgroups. MANOVA revealed that age was directly associated with elevated lipids in men and women. There was no significant relationship between reactivity and lipids for either older or younger men. Conversely, young women showed a significant direct relationship between reactivity and Total Cholesterol and LDL, but this was not present for older women. Implications of these data for the previously reported hypothetical relationship between reactivity and lipids are discussed. Limitations of the study are examined, and future directions for research suggested. PMID- 7880909 TI - Thermal biofeedback in the treatment of intermittent claudication in diabetes: a case study. AB - The objective of the present case study was to examine the therapeutic effects of thermal biofeedback-assisted autogenic training on a patient with non-insulin dependent diabetes mellitus (NIDDM), vascular disease, and symptoms of intermittent claudication. The patient received thermal biofeedback from the hand for five sessions, then from the foot for 16 sessions, while hand and foot skin temperature were monitored simultaneously. In addition, the patient was instructed in autogenic training and practiced daily at home. Follow-up measurements were taken at 12 and 48 months. Within-session foot temperature rose specifically in response to foot temperature biofeedback and starting foot temperature rose between sessions. Posttreatment blood pressure was reduced to a normal level. Attacks of intermittent claudication were reduced to zero after 12 sessions and walking distance increased by about a mile per day over the course of treatment. It would appear that thermal biofeedback and autogenic training are potentially promising therapies for persons with diabetes and peripheral vascular disease. PMID- 7880910 TI - An hypothesis explaining the successful treatment of psoriasis with thermal biofeedback: a case report. AB - This is a single case report of a 56-year-old Caucasian female referred for biofeedback by her dermatologist after seven years of failed standard medical treatment for psoriasis. Patient's presenting complaint was the embarrassing psoriasis lesions on her arms. Following 13 weekly one-hour finger/hand thermal biofeedback treatments, all 11 presenting psoriasis lesions (2-6 cm) had disappeared. Interestingly, any new psoriasis lesions that surfaced during our treatment disappeared without leaving palpable or visible scarring, unlike lesions that were present prior to biofeedback treatment. Patient was unmedicated for psoriasis during our treatment and continues to be unmedicated and asymptomatic at 12-month follow-up. PMID- 7880912 TI - Parallel and serial processes in the human oculomotor system: bimodal integration and express saccades. AB - Saccadic reaction times (SRTs) were analyzed in the context of stochastic models of information processing (e.g., Townsend and Ashby 1983) to reveal the processing architecture(s) underlying integrative interactions between visual and auditory inputs and the mechanisms of express saccades. The results support the following conclusions. Bimodal (visual+auditory) targets are processed in parallel, and facilitate SRT to an extent that exceeds levels attainable by probability summation. This strongly implies neural summation between elements responding to spatially aligned visual and auditory inputs in the human oculomotor system. Second, express saccades are produced within a separable processing stage that is organized in series with that responsible for intersensory integration. A model is developed that implements this combination of parallel and serial processing. The activity in parallel input channels is summed within a sensory stage which is organized in series with a pre-motor and motor stage. The time course of each subprocess is considered a random variable, and different experimental manipulations can selectively influence different stages. Parallels between the model and physiological data are explored. PMID- 7880913 TI - Acquisition of color opponent representation by a three-layered neural network model. AB - This paper discusses color representation in the visual system by analysis of a three-layered neural network model. The model incorporates physiological knowledge of color representation at the sensor level (broad-band trichromatic representation by cones) and the higher level (narrow-band color representation by color-coded cells in V4). We trained the model to perform a mapping between these color representations by the back propagation algorithm and analyzed the acquired characteristics of the hidden units. It turned out that the hidden units learned characteristics similar to those of the color opponent cells found in the visual system. It was concluded that the R-G and Y-B color opponent representations reflect the efficiency of the color representation in the visual system from investigations on the efficiency of color representation in the hidden layer and on the capability of the color recognition task of the model. PMID- 7880914 TI - A neural network model of speech acquisition and motor equivalent speech production. AB - This article describes a neural network model that addresses the acquisition of speaking skills by infants and subsequent motor equivalent production of speech sounds. The model learns two mappings during a babbling phase. A phonetic-to orosensory mapping specifies a vocal tract target for each speech sound; these targets take the form of convex regions in orosensory coordinates defining the shape of the vocal tract. The babbling process wherein these convex region targets are formed explains how an infant can learn phoneme-specific and language specific limits on acceptable variability of articulator movements. The model also learns an orosensory-to-articulatory mapping wherein cells coding desired movement directions in orosensory space learn articulator movements that achieve these orosensory movement directions. The resulting mapping provides a natural explanation for the formation of coordinative structures. This mapping also makes efficient use of redundancy in the articulator system, thereby providing the model with motor equivalent capabilities. Simulations verify the model's ability to compensate for constraints or perturbations applied to the articulators automatically and without new learning and to explain contextual variability seen in human speech production. PMID- 7880915 TI - The fractional-order dynamics of brainstem vestibulo-oculomotor neurons. AB - The vestibulo-ocular reflex (VOR) and other oculomotor subsystems such as pursuit and saccades are ultimately mediated in the brainstem by premotor neurons in the vestibular and prepositus nuclei that relay eye movement commands to extraocular motoneurons. The premotor neurons receive vestibular signals from canal afferents. Canal afferent frequency responses have a component that can be characterized as a fractional-order differentiation (dkx/dtk where k is a nonnegative real number). This article extends the use of fractional calculus to describe the dynamics of motor and premotor neurons. It suggests that the oculomotor integrator, which converts eye velocity into eye position commands, may be of fractional order. This order is less than one, and the velocity commands have order one or greater, so the resulting net output of motor and premotor neurons can be described as fractional differentiation relative to eye position. The fractional derivative dynamics of motor and premotor neurons may serve to compensate fractional integral dynamics of the eye. Fractional differentiation can be used to account for the constant phase shift across frequencies, and the apparent decrease in time constant as VOR and pursuit frequency increases, that are observed for motor and premotor neurons. Fractional integration can reproduce the time course of motor and premotor neuron saccade related activity, and the complex dynamics of the eye. Insight into the nature of fractional dynamics can be gained through simulations in which fractional-order differentiators and integrators are approximated by sums of integer-order high pass and low-pass filters, respectively. Fractional dynamics may be applicable not only to the oculomotor system, but to motor control systems in general. PMID- 7880911 TI - Stress management techniques: are they all equivalent, or do they have specific effects? AB - This article evaluates the hypothesis that various stress management techniques have specific effects. Studies comparing various techniques are reviewed, as well as previous literature reviews evaluating the effects of individual techniques. There is evidence that cognitively oriented methods have specific cognitive effects, that specific autonomic effects result from autonomically oriented methods, and that specific muscular effects are produced by muscularly oriented methods. Muscle relaxation and/or EMG biofeedback have greater muscular effects and smaller autonomic effects than finger temperature biofeedback and/or autogenic training. EMG biofeedback produces greater effects on particular muscular groups than progressive relaxation, and thermal biofeedback has greater finger temperature effects than autogenic training. Disorders with a predominant muscular component (e.g., tension headaches) are treated more effectively by muscularly oriented methods, while disorders in which autonomic dysfunction predominates (e.g., hypertension, migraine headaches) are more effectively treated by techniques with a strong autonomic component. Anxiety and phobias tend to be most effectively treated by methods with both strong cognitive and behavioral components. PMID- 7880916 TI - An associative memory that can form hypotheses: a phase-coded neural network. AB - Nonlinear associative memories as realized, e.g., by Hopfield nets are characterized by attractor-type dynamics. When fed with a starting pattern, they converge to exactly one of the stored patterns which is supposed to be most similar. These systems cannot render hypotheses of classification, i.e., render several possible answers to a given classification problem. Inspired by von der Malsburg's correlation theory of brain function, we extend conventional neural network architectures by introducing additional dynamical variables. Assuming an oscillatory time structure of neural firing, i.e., the existence of neural clocks, we assign a so-called phase to each formal neuron. The phases explicitly describe detailed correlations of neural activities neglected in conventional neural network architectures. Implementing this extension into a simple self organizing network based on a feature map, we present an associative memory that actually is capable of forming hypotheses of classification. PMID- 7880918 TI - A nonlinear regularization approach to early vision. AB - We propose a new class of approaches to smooth visual data while preserving significant transitions of these data as clues for segmentation. Formally, the given visual data are represented as a noisy (image) function g, and we present a class of continuously formulated global minimization problems to smooth g. The resulting function u can be characterized as the minimizer of a specific nonquadratic functional or, equivalently, as the result of an associated nonlinear diffusion process. Our approach generalizes the well-known quadratic regularization principle while retaining its attractive properties: For any given g, the solution u to the proposed minimization problem is unique and depends continuously on the data g. Furthermore, convergence of approximate solutions obtained by finite element discretization holds true. We show that the nodal variables of any chosen finite element subspace can be interpreted as computational units whose activation dynamics due to the nonlinear smoothing process evolve like a globally asymptotically stable network. A corresponding analogue implementation is thus feasible and would provide a real time processing stage for the transition preserving smoothing of visual data. Using artificial as well as real data we illustrate our approach by numerical examples. We demonstrate that solutions to our approach improve those obtained by quadratic minimization and show the influence of global parameters which allow for a continuous, scale-dependent, and selective control of the smoothing process. PMID- 7880917 TI - Modeling motoneuron firing properties: dependency on size and calcium dynamics. AB - The origin of functional differences between motoneurons of varying size was investigated by employing a one-compartmental motoneuron model containing a slow K+ conductance dependent on the intracellular calcium concentration. The size of the cell was included as an explicit parameter. Simulations show that motoneurons of varying size cannot be regarded as simple 'scaled' versions of each other. Rather, they are expected to have intrinsic properties that vary with cell size. These intrinsic properties refer to the membrane conductances per unit area and the dynamics of the intracellular calcium concentration. PMID- 7880919 TI - Simulated control of unilateral, anticipatory locomotor adjustments during obstructed gait. AB - Anticipatory adjustments of our locomotor patterns are necessary in order to negotiate our uneven daily environments. Recent work (McFadyen and Winter 1991) has shown the re-organization of lower limb mechanics for obstacle avoidance during level walking. The present work describes a model which sets the ground work for predicting how such re-organized motor patterns might be generated from stereotypic unobstructed patterns. Pattern-generating algorithms use an estimation of future contacts with obstacles to create weighting functions that modify joint angle trajectories towards new patterns capable of clearing the obstacle. Feedforward/feedback control is then used to generate the necessary joint torques. The results show that model parameters can be found to generate not only kinematic but also energetic patterns for obstacle clearance that mimic experimental results. The validity of the model with respect to human locomotor control is discussed. PMID- 7880920 TI - Topography of alpha and theta oscillatory responses upon auditory and visual stimuli in humans. AB - Brain resonance phenomena and induced rhythms in the brain recently gained importance in electroencephalographic, magnetoencephalographic and cellular studies (Basar and Bullock 1992). It was hypothesized that evoked potentials are superpositions of induced rhythms caused by resonance phenomena in neural populations (Basar et al. 1992). According to Basar (1972), such resonance phenomena are reflected in the main peaks of the amplitude frequency characteristics computed from EEG responses. The present study is based on a frequency domain approach for the evaluation of topography- and modality dependent properties of oscillatory brain responses. EEG and evoked potentials were recorded from vertex, parietal and occipital scalp locations in 24 volunteers. Two combined methods were applied: (1) amplitude frequency characteristics were computed from the transient evoked responses, and (2) frequency components of the transient responses were obtained by adaptive digital filtering. Our main goal was to investigate theta (4-7 Hz) and alpha (8-15 Hz) response components. (1) Amplitude frequency characteristics. Auditory stimuli elicited theta-alpha compound responses in the 4-11 Hz frequency band (e.g. typical peaking frequency around 7 Hz for vertex recordings). Visual stimuli elicited alpha responses (e.g. typical peaking frequency for vertex recordings around 9-12 Hz). Frequency maxima for visual stimuli thus had main peaks at higher frequency values than frequency maxima for auditory stimuli. (2) Digital filtering confirmed these results: for vertex recordings, theta vs. alpha response amplitudes were 9 muV vs 6 muV for auditory stimuli and 5 muV vs 5 muV for visual stimuli, thus confirming a shift towards higher frequencies, i.e. a more prominent contribution of the alpha range, in the case of visual stimulation. We hypothesize that these properties might reflect site- and modality-specific features of stimulus encoding in the brain in which resonance properties of neuron populations are involved. Furthermore we emphasize the utility of the systems theory approach for a better understanding of brain function by means of EPs. PMID- 7880921 TI - Functional aspects of evoked alpha and theta responses in humans and cats. Occipital recordings in "cross modality" experiments. AB - A systems theoretical approach was used to compare possible functional roles of theta (4-7 Hz) and alpha (8-15 Hz) response components of brain evoked potentials. These response components were described earlier by Basar (1980). We recorded EEG and evoked potentials (EPs) from occipital scalp locations in 11 subjects. We used auditory and visual stimuli as inadequate and adequate stimuli, respectively ("cross-modality" measurements). The combined EEG-EP epochs were analysed in frequency domain with fast Fourier transform and adaptive digital filters. Alpha (8-15 Hz) response components turned out to be dependent on whether the stimulus was adequate or not (median amplitude with inadequate vs. adequate stimulation: 1.9 muV vs. 4.0 muV). Theta (4-7 Hz) response components were less dependent on stimulus modality (inadequate vs. adequate stimulation: 2.1 muV vs. 2.8 muV). In EP recordings the occipital alpha response almost disappeared in the first 250 ms following auditory stimulation. Comparable behaviour was observed in similar experiments with recordings from the cat visual cortex (area 17) and with occipital magnetoencephalographic recordings. Taking into account the above-mentioned previous reports on intracranial recordings in primary sensory areas of the cat brain and preliminary results of magnetoencephalographic measurements, we propose the following hypothesis: alpha responses in a time window of about 250 ms after stimulation might predominantly reflect primary sensory processing whereas the theta responses in the first 250 ms after stimulation might be more involved in supra-modality - or cross-modality - associative-cognitive processing. PMID- 7880922 TI - A modified radial isochron clock with slow and fast dynamics as a model of pacemaker neurons. Global bifurcation structure when driven by periodic pulse trains. AB - A simple mathematical model of living pacemaker neurons is proposed. The model has a unit circle limit cycle and radial isochrons, and the state point moves slowly in one region and fast in the remaining region; regions can correspond to the subthreshold activity and to the action potentials of pacemaker neurons, respectively. The global bifurcation structure when driven by periodic pulse trains was investigated using one-dimensional maps (PTC), two-dimensional bifurcation diagrams, and skeletons involving stimulus period and intensity. The existence of both the slow and the fast dynamics has a critical influence on the global bifurcation structure of the oscillator when stimulated periodically. PMID- 7880923 TI - Tumorous manifestation of hairy cell leukemia after long-term treatment with interferon alpha. AB - Tumorous-manifestation of hairy cell leukemia in a patient treated with IFN alpha for 7 years is described. After this time, while the patient still was in hematological remission, a tumorous involvement of the lung by hairy cells developed and was successfully treated by surgery. No differences in the phenotype of hairy cells in the lung tumor, in the bone marrow, or in the blood could be detected. PMID- 7880924 TI - Erythema nodosum as a presenting feature of T-cell-rich B-cell lymphoma. PMID- 7880925 TI - Sequential induction chemotherapy with vincristine, daunorubicin, cyclophosphamide, and prednisone in adult acute lymphoblastic leukemia. AB - Sequential chemotherapy with vincristine, daunorubicin, cyclophosphamide, and prednisone doses was administered to 57 adult patients with acute lymphoblastic leukemia (ALL). Complete remission (CR) was achieved in 51 (89%, 95% confidence intervals, [CI] 78-96%). Among patients achieving CR, 62% were in CR after one sequence of chemotherapy, 23% after two sequences, and 5% after three sequences. Six patients (11%) had resistant disease. All patients experienced profound myelosuppression. Median time to recovery of neutrophils > 0.5 x 10(9)/1 was 22 days (range: 5-89 days), and of platelets > 100 x 10(9)/1 21 days (range: 0-45 days). Nonhematologic WHO grade 3 or more side effects consisted predominantly of hyperbilirubinemia (7%), mucositis (5%), nausea and vomiting (2%), and cutaneous toxicity (1%). Severe infectious complications occurred in only 14% of cases. One patient (2%, 95% CI 0-9%) died of therapy-related toxicity while in early CR. We concluded that sequential use of prednisone seemed at least as effective as continuous administration at the expense of a few adverse side effects. PMID- 7880926 TI - High-dose Ara-C for remission induction and consolidation of previously untreated adults with ALL or lymphoblastic lymphoma. AB - Thirty-two patients with untreated ALL (n = 26) or lymphoblastic lymphoma (n = 6) between 17 and 65 years of age were treated with a short remission induction course with VP16-213, amsacrine, intermediate dose Ara-C for 6 days, prednisone and intrathecal methotrexate, followed by a consolidation course with vincristine, amsacrine, high dose Ara-C for 4 days, prednisone and intrathecal methotrexate. After subsequent cranial irradiation, no further maintenance was planned. However, some patients underwent an allogenic (n = 5) or autologous (n = 5) bone marrow transplantation after the consolidation treatment. Twenty-three of 32 patients (72%) achieved a complete remission. Ten of 13 patients with T-ALL or lymphoma, six of eight patients with pre-B or common ALL, and seven of 11 patients with B-ALL or Burkitt's lymphoma achieved a complete remission. The median duration of remission was 24 months. Overall survival for the whole group was 35% at 5 years. The disease-free survival was 45% at 5 years. Long-term survival for patients with B or T-ALL was approximately 60%, compared with 15% for those with common or pre B-ALL. Short term intensive courses including intermediate or high dose Ara-C during remission and consolidation treatment lead to results comparable to those obtained with long-term maintenance regimens. Our regimen may be sufficient for patients with T or B-ALL. Larger randomized studies are needed to investigate the relative importance of our observations. PMID- 7880927 TI - Early detection of minimal residual disease by reverse transcriptase polymerase chain reaction predicts relapse in acute promyelocytic leukemia. AB - The PML/RAR alpha fusion RNA can be detected in acute promyelocytic leukemia (APL), cytogenetically characterized by the translocation t(15;17). Our study included ten newly diagnosed patients with APL who were investigated during the course of their diseases using reverse transcription polymerase chain reaction (RT-PCR). At diagnosis, aberrant fragments with a size heterogeneity due to alternative spliced products were detected in all patients, we observed breakpoints within bcr3 (short type) in two patients and bcr1 and 2 breakpoints (long type) in eight patients. Treatment consisted of all-trans retinoic acid (ATRA) in all patients; six patients received simultaneous cytostatic therapy during remission induction. At the time of complete hematological remission (CR), only two patients showed a negative RT-PCR result; eight of the ten patients were still PCR positive when nested primers were used. Subsequently, eight patients received consolidation chemotherapy and became PCR negative. Seven of eight patients are in continuous complete remission (median remission duration: 21 months, range: 11+ -26+ months). One patient of the chemotherapy group became PCR positive after 4 months in complete remission and relapsed after 6 months. The remaining two patients who were treated only with ATRA relapsed, received induction chemotherapy, and are in second and third complete remission, respectively. In conclusion. PCR negativity can be achieved only by chemotherapeutic consolidation; patients treated with ATRA alone remain PCR positive. Relapse is always preceded by a positive PCR result. Surprisingly, also patients without measurable PML/RAR alpha-mRNA in sequential analyses after cytostatic treatment became PCR positive and experienced relapse. PMID- 7880928 TI - Chronic myelogenous leukemia and exposure to ionizing radiation--a retrospective study of 443 patients. AB - Exposure to ionizing radiations (Rx) has been implicated as a causative factor of chronic myelogenous leukemia (CML). We performed a retrospective study of 443 consecutive CML patients, looking for a history of significant exposure to Rx, and evaluated the clinical and hematological characteristics in order to find any difference between radiation-related CML patients and those with de novo CML. We identified 406 patients without known exposure to mutagens (group I) and 37 patients with prior significant exposure to Rx (group II). In comparison to patients of group I, those of group II showed particular clinical and hematological features: significantly lower incidence of bulky splenomegaly (p < 0.05) and hyperleukocytosis (WBC > 100 x 10(9)/l; p < 0.05); significantly higher incidence of anemia (Hb < 10 g/dl; p < 0.01). Patients with radiation-related CML had a significantly better survival than those with de novo CML (median survival 61 months vs 42 months; p < 0.05). In conclusion, this study of a large cohort of CML patients indicates that the subgroup of patients with a history of significant exposure to ionizing radiation has particular clinical and hematological features at onset (lower tumor burden, higher frequency of anemia) and a better survival. PMID- 7880929 TI - An open study on the safety and efficacy of fluconazole in the treatment of disseminated Candida infections in patients treated for hematological malignancy. AB - Disseminated candidiasis is a serious infectious complication with a mortality as high as 50%. Standard therapy consists of parenteral amphotericin B which is associated with major side effects and prolonged hospitalization. The aim of the study was to assess the efficacy and safety of fluconazole in an open, noncomparative study. Fluconazole, as a single agent, was given intravenously for the first 3 days at a dose of 200 mg twice daily, followed by 200 mg twice daily orally until resolution of signs and symptoms or evident treatment failure. The study group comprised 24 consecutive patients of whom nine had acute and 15 chronic disseminated candidiasis. A clinical response was achieved in 67% of cases of acute disseminated candidiasis and in 86% of cases of chronic disseminated candidiasis. The median duration of therapy was 15 days and 6 months, respectively. Superinfections with Aspergillus fumigatus developed in five patients who were persistently neutropenic. No drug-related toxicity was registered. PMID- 7880930 TI - Failure of repeated courses of high-dose intravenous immunoglobulin to induce stable remission in patients with chronic idiopathic thrombocytopenic purpura. AB - Repeated courses of HD IVIg are reported to induce stable remission in a significant proportion of adults with chronic refractory ITP. We have treated 14 such patients obtaining a remission rate quite comparable to the 5-10% of spontaneous remission. PMID- 7880931 TI - Emperipolesis of marrow cells within megakaryocytes in the bone marrow of sublethally irradiated mice. AB - The incidence of megakaryocytic emperipolesis was studied in the bone marrow of normal and X-irradiated mice. Two groups of mice received total body irradiation with a single dose of 5 Gy and one of the two groups had been treated with a radioprotective drug, ethiofos (WR-2721), before irradiation. Mice from a third group remained unexposed to irradiation and served as controls. The Wright-Giemsa stained bone marrow smears were analyzed every 5 days during a 30-day period, starting 1 day after irradiation. The number of megakaryocytes exhibiting the phenomenon was determined and expressed as an average value for every experimental group. The frequency of megakaryocytic emperipolesis was less than 15% of megakaryocytes from control smears but increased to 34% in mice that had only been irradiated and to 43% when mice were treated with WR-2721 before irradiation. In the last case, i.e., irradiation and treatment with a radioprotective drug, a positive correlation between the macrocytic megakaryocytes and elevated emperipolesis was noted. Under light microscopy, there were no signs of phagocytosis; engulfed cells remained unaltered with their normal structure intact. Granulocytic, erythroid, and lymphoid cells appeared to be the most frequent marrow cells engulfed by mature megakaryocytes. The number of incorporated cells in one megakaryocyte ranged from 1 to 3, though occasionally more than 6 were seen in macrocytic megakaryocytes. Based on our findings and on a review of the associated literature, we believe emperipolesis is an interesting cellular phenomenon related to the fast passage of marrow cells across the marrow-blood barrier, especially through the cytoplasm of megakaryocytes in response to an increased demand for cell delivery. The high demand for cell delivery which occurs after irradiation may cause certain mature bone marrow cells to take a transmegakaryocyte path to enter the circulation of the blood. Irradiation seems to have an immediate effect (observed after 24 h) on emperipolesis, suggesting that a humoral factor is involved in the pathogenesis. PMID- 7880932 TI - Quality of pooled platelet concentrates prepared from buffy coats and stored in an additive solution after filtration. AB - Platelet concentrates prepared from buffy coat were pooled and stored for 6 days after removal of leukocytes by filtration. The platelets were stored in plasma or in an additive solution, Plasmalyte-A. In vitro platelet function was better preserved using Plasmalyte-A than plasma with regard to osmotic reversal and aggregation. No significant differences for the release of platelet markers beta thromboglobulin, platelet factor 4, or lactate dehydrogenase pre- and post filtration and storage in plasma or Plasmalyte-A was observed. Expression of the surface membrane glycoproteins Ib, Ia/IIa, IIb/IIIa, and IV measured by flow cytometry after binding of monoclonal antibodies did not change during storage. The expression of activation-dependent alpha-granula glycoprotein GMP140, the thrombospondin, and the glycoprotein 53 from the lysosomal granules was not different between platelet pools stored in plasma or in Plasmalyte-A. The in vitro quality of platelets stored as pools is comparable for plasma and the additive solution Plasmalyte-A. PMID- 7880933 TI - Birth and fertility rates for states: United States, 1990. PMID- 7880934 TI - Longitudinal changes in symptoms and plasma homovanillic acid levels in chronically medicated schizophrenic patients. AB - A correlation has been noted between the changes in plasma homovanillic acid concentrations and changes in psychiatric symptoms induced by neuroleptic treatment. Our objective was to determine whether plasma homovanillic acid concentration changed in accordance with the changes in symptoms over time. Twenty-eight chronically medicated schizophrenic inpatients received the same treatment regimen for 1 year. Symptoms and plasma homovanillic acid concentrations were examined every month and whenever conditions deteriorated. Plasma homovanillic acid concentrations were significantly higher in the patients in the worst condition than in the patients in the best condition. Further, when comparing the best and worst conditions of both the positive and negative symptoms, the change in psychiatric rating of positive and negative symptoms was correlated significantly with the change in plasma homovanillic acid level. These results suggest that a change in plasma homovanillic acid concentration can be produced not only by neuroleptic-induced dopaminergic blocking but also by a change in positive and negative symptoms of schizophrenia. PMID- 7880935 TI - Visible persistence decay rates for schizophrenics and substance abusers. AB - Information-processing deficits are consistently reported for schizophrenics. The findings from the majority of psychophysical tasks indicate that the deficit is specific to schizophrenics and thus may represent a marker for schizophrenia. The present study evaluated for specificity of impairment by including controls using methadone. A two-pulsed forced choice information-processing task that required the detection of a line or a blank-field during an interstimulus interval (ISI) indexed efficiency of processing (i.e., visible persistence). There were 19 schizophrenic, 9 schizoaffective, 8 depressed, 12 on methadone, and 12 normal subjects. The visual stimuli were low and high spatial frequency gratings. Either a line of equivalent width to those of the gratings or a blank field was presented during the ISI. The gratings were presented for 150 msec prior to and following an ISI of 30, 60, 90, 120, 150, and 350 msec. The results support previous findings for impaired processing during a 90-150 msec interval for schizophrenics. Also, the methadone-using controls were not significantly different from schizophrenics. Normal and depressed controls' profiles did not differ from each other, however, they were significantly different from the other groups. The results support an early information-processing deficit in schizophrenic individuals and may implicate dysregulation of dopaminergic neuromodulation. PMID- 7880936 TI - Sensorimotor gating and habituation evoked by electro-cutaneous stimulation in schizophrenia. AB - The present study has been performed in order to evaluate two relevant phenomena related to startle reflex (SR) evoked by electro-cutaneous stimulation in schizophrenic patients: 1) the effect of different interstimulus intervals on R1, R2 magnitude and on R2 latency in schizophrenia in order to verify if the gating effect influences all blink reflex (BR) parameters and 2) to replicate and extend our previous data on SR habituation. Our data have confirmed the existence of an impairment of habituation and an abnormal facilitatory effect of R1 component of BR in schizophrenics compared to healthy controls. The present study provides further evidence of specific defective mechanisms of information processing in schizophrenia. The methodology used for SR paradigm appears to be founded on a sound research basis and represents an advantageous paradigm for assessing attentional variables of information processing in mental disorders. PMID- 7880937 TI - Flinders resistant hypocholinergic rats exhibit startle sensitization and reduced startle thresholds. AB - Based on the hypothesis that depression involves a cholinergic-adrenergic neurotransmitter imbalance, a putative genetic animal model of depression has been developed by selectively breeding rats to exhibit hypocholinergia (Flinders Resistant Line--FRL), or hypercholinergia (Flinders Sensitive Line--FSL). The present experiments were designed to test the behavioral reactivity of these rats to external stimuli by measuring acoustic startle responses. The FRL rats exhibited lower startle thresholds compared to both FSL and control rats, while the FSL rats' startle thresholds were between those of controls and FRL rats. Despite the differences in thresholds, the three groups demonstrated similar levels of maximal startle reactivity to a high-intensity acoustic stimulus. With repeated stimulus presentations, FRL rats developed startle sensitization, a rarely observed phenomenon, while FSL and control rats exhibited habituation. There were no differences between the three groups in prepulse inhibition of startle. These results indicated that FRL rats exhibited interesting startle phenomena that are characteristic of certain psychiatric disorders, such as schizophrenia, post-traumatic stress disorder, and, potentially, depression. PMID- 7880938 TI - Arginine but not pyridostigmine, a cholinesterase inhibitor, enhances the GHRH induced GH rise in patients with anorexia nervosa. AB - Pirenzepine, a muscarinic antagonist probably acting via stimulation of hypothalamic somatostatin release, abolishes the growth hormone releasing hormone (GHRH)-stimulated growth hormone (GH) rise in normal subjects but only blunts it in patients with anorexia nervosa (AN). This finding suggested the existence in AN of an alteration of cholinergic system and/or somatostatinergic tone. To further investigate these mechanisms, in 11 AN women patients (age 18.8 +/- 0.9 years; BMI 13.4 +/- 0.4) we studied the GH response alone (1 microgram/Kg IV as a bolus at 0 min) and combined with pyridostigmine (PD, 120 mg orally, 60 min before GHRH administration), a cholinesterase inhibitor, or arginine (ARG 30 g infused over 30 min starting at 0 min), two compounds probably acting via inhibition of hypothalamic somatostatin (SS) release. The GH response to GHRH preceded by a previous (120 min before) neurohormone administration also was studied. All these tests also were performed in 20 normal age-matched women (age 22.0 +/- 1.8 yrs; BMI20.1 +/- 2.4). Basal serum GH levels were higher in AN patients than in normal volunteers (NV) (10.3 +/- 3.4 versus 2.8 +/- 0.3 microgram/L; p < 0.001), whereas plasma IGF-I levels were lower in AN patients than in NV (43.3 +/- 10.6 versus 172.4 +/- 13.9 micrograms/L; p < 0.00001). In AN patients, GHRH administration induced a GH rise higher, though not significantly, than that in NV [delta area under the curve (AUC) 1173.6 +/- 167.6 versus 834.6 +/- 188.1 micrograms/L/h]. The GH response to the second of two consecutive GHRH boluses was lower (p < 0.01) than that of the first one either in AN patients or in NV (67.6 +/- 27.4 and 53.1 +/- 25.7 micrograms/L/h, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880939 TI - Twenty-four-hour food intake in patients with anorexia nervosa and in healthy control subjects. AB - Ad libitum feeding over 24 hours was assessed in underweight restrictor anorectic (RAN) women (n = 8) and matched healthy control subjects (n = 9) in a relatively naturalistic laboratory setting. RAN consumed 828 +/- 210 kcal/day (20 +/- 6 kcal/kg/day); controls ingested 2274 +/- 564 kcal/day (41 +/- 13 kcal/kg/day). Expressed as macronutrient consumption, RAN, compared to healthy controls, ate less fat (13% vs 31%), more carbohydrate (73% vs 57%), and similar amounts of protein (14% vs 12%). RAN initiated fewer eating episodes than controls (4 vs 7). This study quantitatively confirms the growing body of evidence suggesting that RAN avoid fat-containing foods. Such persistent fat avoidance may significantly contribute to the difficulty RAN experience in gaining and maintaining body weight. PMID- 7880940 TI - Effects of traumatic stress on defensive burying: an alternative test of the learned helplessness animal model of depression and enhanced retrieval of unpleasant memories. PMID- 7880941 TI - Decreased parameters of heart rate variation in amitriptyline treated patients: lower parameters in melancholic depression than in neurotic depression--a biological marker? PMID- 7880942 TI - Cerebrospinal fluid acetylcholinesterase homospecific activity in patients with "probable Alzheimer's disease". PMID- 7880943 TI - Polydipsia and hippocampal pathology. PMID- 7880944 TI - The N2 event-related potential reflects attention deficit in schizophrenia. AB - Schizophrenia involves deficits in detection and filtering of irrelevant stimuli. The N2 event-related potential (ERP), most likely reflecting classification of deviant stimuli, remains largely unstudied in this group. Recently, we reported that N2 amplitude correlated highly with reduced neocortical and medial temporal lobe volumes in schizophrenics. However, little is known about the functional properties of N2 in schizophrenics. To that end, the latency and amplitude of N2 were assessed in schizophrenic and control subjects to differently pitched tones. Subjects pressed a button in response to low probability (p = .15) target tones interspersed among high probability standard tones. Tones were either NEAR (1.4 kHz standard, 1.5 kHz target) or FAR (1 kHz standard, 1.5 kHz target) in pitch. N2 was measured from difference waveforms, subtracting ERPs on a simple reaction time task (target p = 1.0) from those of the detection task. Schizophrenics performed the detection task nearly as well as controls in the FAR condition, and more poorly in the NEAR condition. Schizophrenics displayed virtually no N2 amplitudes in either condition. The results are interpreted as electrophysiological signs of disturbance in stimulus classification and attention processes in schizophrenia directly related to pathology of N2 neural generators, independent of sensory or detectability problems. PMID- 7880945 TI - Season, gender, and P300. AB - Light therapy in patients with seasonal affective disorder has been reported to enhance visual P300 amplitude. This findings raises the possibility that variations in P300 occur naturally in nonpatients as a function of seasonal variation in sunlight. In the present investigation, P300 was studied in a sample of psychiatrically screened normal subjects who were tested at different times of the year. P300 was larger in women than men and varied in relation to season. This pattern is relevant to studies in which subjects are tested under varying sunlight conditions, such as different seasons. In addition, variations in P300 in normal subjects may be relevant to an understanding of the effectiveness of light therapy for patients with seasonal affective disorder. PMID- 7880946 TI - Volitional vasomotor lability and vasomotor control. AB - This experiment tested the hypothesis that skin temperature variability during instructions to attempt skin temperature self-control without feedback (volitional vasomotor lability) predicts the acquisition of vasomotor control through biofeedback training. Skin temperature was recorded from the hands of 232 volunteers during a screening session. Twenty-three labile and 17 stabile subjects were chosen to participate in a 16-session training program under double blind conditions. Visual and auditory feedback were used to train subjects to produce temperature differences between the two hands in a specified direction. Comparisons between the labile and stabile groups revealed statistically significant differences in the predicted direction on measures of performance and learning. These findings provide preliminary support for the hypothesized positive relationship between volitional temperature variability and voluntary vasomotor control. Fruitful directions for future research are suggested. PMID- 7880947 TI - Interaction between extraversion and drug-induced conditions as indicated by the contingent negative variation. AB - The effects of chlordiazepoxide, caffeine and placebo on the contingent negative variation (CNV) in relation to extraversion were investigated in a double-blind study. Forty-four healthy naive volunteers, varying in extraversion scores, took part in the study. The baseline values of the O wave, E wave and average CNV amplitudes decreased significantly in successive experiments for individual subjects. Administration of the drugs caused a change in the amplitude of the O wave from baseline, whereas placebo effects were negligible. For chlordiazepoxide the change was positive at the lower end of the extraversion score and negative at the upper end, while for caffeine the opposite was found. For the individual drugs the correlations with the change in O wave and extraversion score were not significant (P < 0.20 in the case of both drugs). Analysis of the difference in the effect on O wave between the drug and the placebo yielded a significant negative correlation for chlordiazepoxide (P < 0.05) whereas the positive correlation for caffeine was not significant (P < 0.40). The individual differences between the effects of chlordiazepoxide and caffeine on O wave correlated significantly with the extraversion score (P < 0.02). This difference was positive at the lower end of the extraversion score and negative at the upper end. The same trend was found in the case of E wave and average amplitude but not significantly so. This finding supports the hypothesis that CNV is an indicator of the interaction between extraversion and condition. PMID- 7880948 TI - [An ethics for the future of the primary care team]. PMID- 7880949 TI - [The validity and reliability of arterial pressure measurement in a health center]. AB - OBJECTIVE: To evaluate the validity of blood pressure measurement by studying the presence of preference bias in last digits and also of the bias which tends to situate measurements below the established limit. To evaluate the interobserver (doctor-nurse) reliability of the measurements. DESIGN: A cross-sectional [correction of crossover] observation study with descriptive and analytic components. SETTING: A nursing station in the Health Centre. PATIENTS: The patients who attended the nursing station by appointment during the months of September and October 1993. MEASUREMENTS AND MAIN RESULTS: The patients who attended the nursing station by appointment had their blood pressure measured by a doctor or nurse in a random fashion. We detected a preference in last digits, which was very significant for both systolic and diastolic pressure (p < 0.0001). The tendency to reduce diastolic figures to below the preestablished limit of pressure was also very significant (p < 0.05). The nurse found lower figures than the doctor, with a very significant difference for diastolic pressure (p < 0.001). The index of kappa concordance between nurse and doctor on evaluating whether pressure was high or not was 0.4864, with a C.I. of 95%, from 0.3530 to 0.6198. CONCLUSIONS: The existence of two important biases in the measurements of pressure questions their validity. Additionally the significant difference between the pressure averages and the low concordance poses a serious question over the interobserver reliability and should make us restate blood pressure measurement and the treatment of patients suffering Hypertension. PMID- 7880950 TI - [The detection of factors predictive of the abandonment of disabled patients in a basic health area]. AB - OBJECTIVE: MAIN OBJECTIVE: to elaborate a Persons at Risk Index (PRI) for the abandonment of elderly handicapped. SECONDARY OBJECTIVES: to discover the profile of these invalids and their carers within our Health District. DESIGN: A case control study. A uni- and multi-variant analysis (multiple logistic regression). SETTING: An urban Health Centre. Programme for the Care of the handicapped Patient. PATIENTS AND OTHER PARTICIPANTS: 1. Handicapped patients (those unable to attend the Health Centre for care) who were included in the Programme in December 1991 (Total = 177). 2. Carers (those with direct responsibility in caring for the sick). 106 handicapped patients were interviewed (33 took part in the pilot study, 13 died, 1 entered hospital, 16 refused to answer and 8 were not located). 20 patients (19%) were identified as being abandoned invalids, with abandon being defined as not having their need for help in their daily activities covered. The other 86 (81%) were considered as controls. MEASUREMENTS AND MAIN RESULTS: Profile of the handicapped patient: woman > 76 years old, illiterate, housewife, widow. Profile of career: woman, daughter or wife of the invalid, between 50 and 65, house-wife, uneducated. The variables selected by the multiple model as being linked to abandonment show greater risk for invalid patients living in zones of high social risk, who lack a specific career or have only been looked after by their present career for a brief period. CONCLUSIONS: The PRI is an instrument which serves for predicting those invalids most likely to be abandoned, an undesirable situation to be avoided by prioritizing health service interventions. PMID- 7880951 TI - [Alcohol consumption and the diagnosis of alcoholic patients in primary care]. AB - OBJECTIVE: To find the frequency of investigation of alcohol-related problems and how often alcoholic patients are identified in primary care. DESIGN: A descriptive cross-sectional [correction of crossover] study. SETTING: An urban health centre. PATIENTS: 219 patients over 15 who attended an appointment occasioned by a CAGE questionnaire validation study. 108 had answered affirmatively some of the questions in the test and 111 had answered the four questions negatively. MEASUREMENTS AND MAIN RESULTS: Diagnoses of alcoholism based on the fulfillment of the DSM-III criteria and/or on the presence of alcoholic consumption of > or = 60 grammes per day for men or 30 grammes per day for women were investigated. Additionally, each patient's medical records were checked to see whether their habitual alcohol consumption or a diagnosis of alcoholism were recorded. 54 patients were diagnosed as alcoholic. Previous inquiries into consumption of alcohol were recorded in the medical records of 167 patients (76.2%). A diagnosis of alcoholism was found to be recorded in 19 of the 54 patients who fulfilled the diagnostic criteria of our study (35.2%) and in 3 patients who did not fulfil those criteria. CONCLUSIONS: Although good records of patients' habits of alcohol consumption existed, 64.8% of those diagnosed as alcoholic in our study had not been previously identified as such. This must lead us to question the efficacy of our usual diagnostic methods. PMID- 7880952 TI - [Demographic classification of the family in the basic health area of La Orden, Huelva]. AB - OBJECTIVE: To find the prevalence of different family structures in our health district. DESIGN: An epidemiological study of a cross-sectional [correction of crossover] type. SETTING: Primary Care. La Orden Health Centre in Huelva. PARTICIPANTS: 878 individuals, who represented a family unit, selected by random sampling stratified by age and gender, obtained from the 1991 Municipal Census. MEASUREMENTS AND MAIN RESULTS: A questionnaire was administered to all those participating in the study. This included demographic data, the number of people living in their homes, the composition of their family and the presence of close relatives in the neighbourhood. The final sample covered 787 families. Using de La Revilla et al.'s proposal, partially modified by us, the family was classified as: nuclear, extended, single-parent, without family and family equivalents. All of these were in turn sub-classified for the presence of close relatives. The nuclear family was classified as simple, numerous, amplified or binuclear. The predominant family model was nuclear (89.7%), followed by single-parent (4.4%), extended (2.9%), without family (2.4%) and family equivalents (0.6%). The main model of the nuclear family was the simple one (76.5%), followed by amplified (15.4%), leaving the numerous family in 8.1% and the binuclear at 0%. 83.5% of our families had close relatives in the same neighbourhood. CONCLUSIONS: Our family is nuclear, with relatives nearby, a model which has definitively displaced the extended family. The structure proposed makes classification of the nuclear family easier. We believe it is essential to integrate family structure classification into Primary Care family clinical records. PMID- 7880954 TI - [Bioethics and terminal illness. Does Spain need a euthanasia law?]. PMID- 7880953 TI - [Occupational asthma]. AB - OBJECTIVE: Description of three cases of work-related asthma. DESIGN: Retrospective clinical observations. SETTING: Primary care clinics in the centre of the metropolitan health area of Madrid. PATIENTS: A 19-year old male who worked in the manufacture of Psyllium and reported one month's evolution of an irritative cough on getting up in the morning. A 33-year-old male who worked as a car mechanic and reported episodes of respiratory difficulty while at work. A 17 year-old male employed by a bread manufacturer who attended because of a catarrhal condition accompanied by respiratory difficulty. MEASUREMENTS AND MAIN RESULTS: The maximum expiratory flow monitor (MEFM) was used to measure maximum expiratory flow (MEF) in two patients. The third was temporarily separated from his work environment. The monitoring of the MEF showed a slow fall of 25% in the patient who worked with Psyllium and a rapid fall of 36% in the mechanic, which coincided with the symptoms. The patient with asthma probably caused by flour evolved favourably while off work and deteriorated again on returning to work. The allergological study showed sensitivity to Psyllium, Isocyanate and flour, respectively. The three patients stayed asymptomatic on being separated from the catalysing substances. CONCLUSIONS: The early diagnosis of work-related asthma requires a high level of diagnostic awareness. It is extremely important to separate the patient from the catalysing agent. The MEFM is a very useful instrument of diagnosis for the primary care doctor. PMID- 7880955 TI - [Treatment of the alcohol dependence syndrome. The role of primary care]. PMID- 7880956 TI - [Is antibiotic prescription adequate in primary care?]. PMID- 7880957 TI - [The use of opiates in acute abdomen]. PMID- 7880958 TI - [Alcohol consumption in schoolchildren: motivations and attitudes]. AB - OBJECTIVE: To determine the levels of alcohol consumption among 8th grade (EGB) students in Cuenca, including the predisposing circumstances and factors as well as the children's motivation and attitudes. DESIGN: Descriptive observation study of a cross-sectional [correction of crossover] design. SETTING: Primary Care: the school population of the city of Cuenca. PATIENTS AND OTHER PARTICIPANTS: 672 school-children of both sexes in 8th grade (EGB). MEASUREMENTS AND MAIN RESULTS: An anonymous questionnaire with 30 closed questions was administered. 60% of the school-children had consumed alcohol on some occasion. In 54.94% of cases, friends first invited them to drink alcohol; in 33.59%, a family member. 1.4% of the children admitted to drinking alcohol daily (2.1% of boys against 0.7% of girls). 57.3% of fathers, 24.3% of mothers, 25.8% of brothers and 38% of friends consumed alcohol habitually. 36.9% of the children did not think that alcohol was a drug. CONCLUSIONS: The levels of alcohol consumption in the section of the population studied were high. Children began early and had easy access to alcoholic drinks. The level of consumption in their family and social environment was very high and was related to children's consumption. These results highlight the need for a preventive programme. PMID- 7880959 TI - The importance of polysaccharide configurational entropy in determining the osmotic swelling pressure of concentrated proteoglycan solution and the bulk compressive modulus of articular cartilage. AB - One important contribution to the osmotic swelling pressure of concentrated proteoglycan and hence the elasticity of articular cartilage arises from the configurational entropy of the polysaccharide chains in the extracellular matrix. The work presented here provides a theoretical determination of this entropy and an analysis of its effect on the equilibrium osmotic swelling pressure of concentrated proteoglycan solutions. This effect is calculated in a manner similar to the Flory-Huggins technique where the solution is treated as a lattice (P. Flory, Principles of polymer chemistry (Cornell Univ. Press, Ithaca, 1953); J. Chem. Phys. 12 (1944) 425). In addition, the charge-related contribution to the elasticity of these materials is reviewed in the form of a Donnan equilibrium model (T. Hill, Faraday Soc. Discussions 21 (1956) 31; A.G. Ogston and J.D. Wells, Biochem. J. 119 (1970) 67; C. Tanford, Physical Chemistry of Macromolecules (Wiley, New York, 1961)). It is found that the configurational entropy of the glycosaminoglycan (GAG) chain polysaccharides together with the charge effects reproduce the equilibrium swelling pressure of concentrated proteoglycan solutions as experimentally determined by J.P.G. Urban et al., Biorheol. 16 (1979) 447. In addition this theoretical model is manifestly independent of the proteoglycan molecular weight, consistent with prior experimental findings (J.P.G. Urban et al., Biorheol. 16 (1979) 447). The model is also extended to include polydispersity of proteoglycan size and to predict the equilibrium bulk compressive modulus of articular cartilage. This work represents the first comprehensive theoretical description of the equilibrium elastic properties of proteoglycan solutions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880961 TI - Solution X-ray scattering study on the chaperonin GroEL from Escherichia coli. AB - The molecular architecture of native GroEL has been studied by solution X-ray scattering. The radius of gyration for the native molecule was estimated to be 66.0 A in 50 mM Tris-HCl, 100 mM KCl at pH 7.5 and 25 degrees C. The maximum dimension was estimated to be 170 A, based on the pair distance distribution function. A cylindrical structure or two heptameric rings was found to be the best for native GroEL among structures examined by using a multi-sphere model analysis in which the radius of constituent sphere was 6 A. The results of the model analysis show that the radius of GroEL is 68.0 A and the height is 150.7 A. Unexpectedly, the central penetrating hole through GroEL was not confirmed in the best-fit structure. PMID- 7880960 TI - Differential binding of RNA polymerase to the wild type Mu mom promoter and its C independent mutant: a theoretical analysis. AB - Using the theoretical model for DNA bending we have analyzed the Mu mom promoter wild type and its mutant tin7 which showed differential binding to the RNA polymerase. We have demonstrated here the structural change as a result of the point mutation which may be responsible for the altered binding of RNA polymerase. Analysis using both sets of parameters essentially gives the same result. PMID- 7880962 TI - Superstructural features of the upstream regulatory regions of two pea rbcS genes and nucleosomes positioning: theoretical prediction and experimental evaluation. AB - Nucleosome positioning on two 384 bp DNA fragments, obtained from the upstream regulatory region of two pea rbcS genes, relevant in photoregulated transcription, was predicted using our theoretical method, based on the evaluation of the sequence dependent DNA bending energy. The theoretical prediction was checked by experimental evaluation of nucleosome positions after in vitro reconstitution, by mapping Exonuclease III-resistant borders and by digesting monomeric sequences with various restriction enzymes. Both approaches satisfactorily confirmed the theoretical predictions, showing that the nucleotide sequence intrinsic bendability has a dominant role in nucleosome positioning. PMID- 7880963 TI - Peptide science. PMID- 7880964 TI - Synthesis of large peptides in solution. PMID- 7880965 TI - Design and synthesis of nonpeptide peptidomimetic inhibitors of renin. AB - The desire to replace the amide backbone of renin inhibitors with a new scaffold led us to explore vinylogous amides (enaminones). An initial attempt proved unsuccessful, a result explained after the fact via docking experiments. Based on this lesson, we designed a different vinylogous amide scaffold which incorporated one or more pyrrolinone rings into the backbone. Three of the four compounds gave IC50S in the 0.6 to 18 microM range. These compounds did not inhibit HIV-1 protease. Taken together, the results reported herein provide insights into the role of hydrogen bonding and steric interactions for binding to renin. PMID- 7880966 TI - Peptide science. Comprehensive reports & reviews. Introduction. PMID- 7880968 TI - The psychological impact of an abnormal smear report: a personal view from a general practitioner. PMID- 7880967 TI - 100 years lock-and-key concept: are peptide keys shaped and guided to their receptors by the target cell membrane? AB - The ideas developed in the Membrane Compartments Theory which allow a quantitative prediction of receptor preference are discussed in terms of our present knowledge of opioid and neurokinin receptor structure. Furthermore, conformations of regulatory peptides interacting with artificial lipid membranes are compared with those of chemically constrained molecules that react selectively with different receptor classes. Striking similarities in the topochemistry of molecules with similar activity were observed. The membrane induced topomers were almost congruent with the artificial topomers that are selectively recognized by the same receptors. PMID- 7880969 TI - Fine needle aspiration of focal liver lesions. AB - Fourteen percutaneous fine needle aspirates (FNAs) of focal liver lesions performed under ultrasound guidance at the Sultan Qaboos University Hospital (SQUH), Oman, between January 1991 and October 1992, are presented. Ten of these were cytologically diagnosed as hepatocellular carcinomas (HCC). The patients' ages ranged from 50 to 70 years and eight of these were males. The important diagnostic cytological criteria of HCC were found to be increased nucleocytoplasmic (N/C) ratio, trabecular pattern, atypical naked nuclei, bile production by malignant hepatocytes and absence of bile duct epithelium. Carcinoembryonic antigen (CEA) positivity of bile canaliculi by cross-reaction with biliary glycoprotein I (BGP I) made possible the differentiation of HCC from metastases. We stress the importance of cell blocks as these often constitute microbiopsies. Ultrasound-guided FNA of focal liver lesions is recommended as a simple, easy and quick procedure. PMID- 7880970 TI - Aspiration cytodiagnosis of pancreatic endocrine tumours. AB - We have reviewed fine needle aspirates from 11 patients with pancreatic endocrine tumours and evaluated the diagnostic criteria as well as those proposed in the literature in an attempt to formulate reliable criteria for the cytological diagnosis of these tumours. As expected, no single criterion was reliable for diagnosis: however, cells with rounded or polygonal rather than a columnar shape, cytoplasmic granularity, and eccentricity of round or oval nuclei with a finely stippled, evenly distributed chromatin pattern were features which, taken together, usually enabled one to make a reliable diagnosis. A striking feature of the smears was the cellular monotony and absence of pleomorphism of the tumour cells. Immunocytochemistry and electron microscopy identified tumour products and confirmed the diagnosis. PMID- 7880971 TI - Comparison of two methods of storing breast fine needle aspirates (FNAs) using oestrogen receptor immunocytochemical assay as a method of evaluating the storage methods. AB - Two methods of storing fine needle aspirates were compared in 14 patients with breast cancer. The methods of storage were: (1) as a Cytospin slide prepared immediately from the aspirated material and stored at -80 degrees C; (2) as a suspension of cells in tissue culture medium, stored at -80 degrees C. The effect of storage on the cells was assessed by means of an oestrogen receptor immunocytochemical assay (ER-ICA). An ER positivity of 100% was obtained by ER ICA staining of cells after storage method 1, whilst all of the specimens stored by method 2 were ER-negative. The data demonstrate that cells stored in tissue culture medium at -80 degrees C are not suitable for ER measurement. The storage method of choice for specimens intended for ERICA is as a Cytospin slide. The ER status of cells deposited on Cytospin slides prepared immediately and stored at 80 degrees C for 2 years could be demonstrated despite the delay in processing the specimen. PMID- 7880972 TI - Identification of aneuploid cells in cytological specimens by combined in situ hybridization and immunocytochemistry. AB - The purpose of our study was the application of non-isotopic in situ hybridization with chromosome-specific repetitive DNA probes for the determination of cytogenetically aberrant cells in routine cytological materials, such as cervical smears and breast tumour aspirates. Hyperdiploid cells in fine needle aspirates (FNA) of breast tumours could be visualized by in situ hybridization with a chromosome 1-specific repetitive DNA probe. However, for the evaluation of a specific cell type in heterogeneous cell populations, i.e. cervical smears, a procedure combining immunocytochemistry and in situ hybridization can be required. Therefore, we developed a combination protocol using beta-galactosidase/ferri-ferrocyanide (blue-green) for immunocytochemistry and peroxidase/DAB (brown-black) for detection of the DNA probe. The described protocol enabled us to distinguish squamous epithelial cells within heterogeneous cell populations. By combining the chromosome 1 DNA probe with a specific cytokeratin marker it was possible to identify the chromosomal abnormal cells within cervical smears. PMID- 7880973 TI - Sebaceous adenoma of parotid gland--a rare tumour diagnosed by fine needle aspiration cytology. PMID- 7880974 TI - p55 and p75 tumor necrosis factor receptors are expressed and mediate common functions in synovial fibroblasts and other fibroblasts. AB - There is increasing evidence that TNF-alpha is a cytokine of major importance in the pathogenesis of rheumatoid arthritis. Since TNF-alpha mediates its effects via high affinity receptors, we were interested in investigating their expression and function in cells from rheumatoid tissue. Synovial fibroblasts derived from rheumatoid synovial tissue are stimulated by TNF-alpha to proliferate and release cytokines, prostaglandins, proteases and protease inhibitors. We have evaluated through which receptor stimulation of DNA synthesis and the release of the proinflammatory agents, IL-6, IL-8 and PGE2 are induced. It was found that rheumatoid synovial fibroblasts express both the p55 and p75 TNF receptor, in a ratio of 4:1. TNF-alpha-stimulated synovial fibroblast DNA synthesis and the release of IL-6, IL-8 and PGE2 was inhibited by antagonist monoclonal antibodies against either the p55 or the p75 TNF receptor, although the blockade of the p55 TNF receptor had a more potent effect than inhibition of the p75 TNF receptor alone. Similarly, specific monoclonal antibodies, agonistic for either the p55 or p75 TNF receptor stimulated synovial fibroblast DNA synthesis, as well as IL-6, IL-8 and PGE2 release. Both p55 and p75 TNF receptors on dermal and gingival fibroblasts were also involved in TNF-alpha-mediated DNA synthesis and IL-6, IL-8 and PGE2 release, although differences in the levels of DNA synthesis and release of inflammatory cytokines and PGE2 were observed between the three fibroblast types. PMID- 7880975 TI - Stimulation of alpha-(methylamino) isobutyric acid uptake by interleukin-1 in human synovial cells. Involvement of a cAMP dependent pathway. AB - After one hour incubation with interleukin-1 beta (IL-1 beta), the uptake of alpha-(methylamino) isobutyric acid (MeAIB) by human osteoarthritic synovial cells appeared significantly increased. This effect, observed with 0.1 to 5 ng/ml of cytokine, was inhibited by cycloheximide, indicating that protein synthesis is involved. In addition, this effect seems mediated by a pertussis toxin-sensitive G protein. Finally, intracellular cAMP concentration measurements, the use of a phorbol ester, protein kinase inhibitors and forskolin+3-isobutyl-1-methylxantine (IBMX) provided evidence that a cAMP-dependent protein kinase is associated with interleukin-1 beta-mediated alpha-(methylamino) isobutyric acid uptake. PMID- 7880976 TI - Synergism between interleukin-8 and tumor necrosis factor-alpha for neutrophil mediated platelet activation. AB - We previously showed that two polymorphonuclear neutrophil (PMN)-derived proteinases, namely cathepsin G (Cat. G) and elastase (HLE), acting in synergy activated nearby platelets in vitro. This cellular interaction could result in a pathology such as the adult respiratory distress syndrome (ARDS). Since elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) were detected in these patients and therefore could be involved in this disease, we looked for their effects in the PMN-platelet cooperation system. Addition of IL-8 to mixed suspensions of PMN and platelets induced weak but significant platelet aggregations. Upon preincubation with TNF-alpha, aggregations triggered by IL-8 were significantly increased. The targets of these cytokines were not the platelets but the PMNs. This was shown by following beta-glucuronidase release and more interestingly by measuring the enzymatic activities of Cat. G and HLE in the supernatant. Inhibition of the platelet response upon addition of a serine proteinase inhibitor, eglin C, clearly demonstrated the involvement of these two enzymes. Taken together, these results constitute an additional argument for the role of the PMN-platelet interaction in ARDS. PMID- 7880977 TI - Cellular localisations of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha mRNA in a parasitic granulomatous disease of the liver, alveolar echinococcosis. AB - Alveolar echinococcosis (AE), an uncommon and very severe parasitic liver disease, can be considered as an "infectious model" of granulomatous disease, where cellular immunity plays a key role in the defence against Echinococcus multilocularis, the larval cestode responsible for the disease. We analysed the localisation of the expression of the pro-inflammatory cytokines IL-1 beta, IL-6 and TNF-alpha mRNA in human AE liver lesions, in the periparasitic granulomas and in the hepatic parenchyma, as well as the phenotypic characteristics of the cells on serial sections. In situ hybridizations, using anti-sense 35S dUTP-labeled IL 1 beta, IL-6 and TNF-alpha riboprobes, were performed on cryostat liver sections; the sense probes were used as negative controls. IL-1 beta, IL-6 and TNF-alpha mRNA were observed in macrophages located at the extreme periphery of the granuloma, between the lymphocytic ring and the liver parenchyma, in patients with active AE. No cytokine mRNA expression was observed in a patient with an abortive case. Only TNF-alpha mRNA was located in the periparasitic area, in cells morphologically identified as macrophages but exhibiting an unusual phenotype (CD 11b-, CD 25+); this particular expression was observed only in those patients with very fertile lesions, associated with centro-granulomatous necrosis. These results show that pro-inflammatory cytokines are consistently produced by macrophages at the periphery of the periparasitic granuloma and can serve as mediators of acute-phase protein secretion and of fibrogenesis in that location.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880978 TI - In situ hybridization and cytofluorometric analysis of cytokine mRNA during in vitro activation of human T cells. AB - We present an original method for in situ hybridization (ISH) using non isotopic probes and flow cytometry analysis that permits rapid detection of lymphokine transcripts at single cell level in an in vitro activated human Jurkat T cell line and in peripheral blood T cell subsets. After PMA and either ionomycin or ConA stimulation, cells were fixed and hybridized with digoxigenin (DIG)-labelled RNA antisense or sense probes specific for IL-2 and IFN-gamma. The level of cytokine gene expression in individual cells was visualised using FITC-conjugated anti-DIG antibody, and the resultant signal was analysed by flow cytometry. IL-2 mRNA was first detected in activated Jurkat T cells. Addition of cycloheximide 4 hours after the beginning of stimulation increased both the frequency of labelled cells and the amount of mRNA per cell, as determined by the mean fluorescence intensity. The specificity and sensitivity of IL-2 mRNA detection were tested by comparison with Northern blot analysis and in situ hybridization (ISH) with immuno-cytochemical staining. IL-2 and IFN-gamma mRNA were detectable in PBMC as early as 3 hours after in vitro stimulation with PMA and ionomycin. The frequency of positive cells and the amount of mRNA per cell peaked at 6-8 hours, when the percentages of IL-2 and IFN-gamma mRNA-containing cells reached 30-40% and 15 20%, respectively. The two lymphokines were expressed in both CD4+ and CD8+ T cells, but the frequency of IL-2 expressing cells and the amount of IL-2 mRNA per cell were higher in CD4+ (60%) than in CD8+ T cells (25%), whereas IFN-gamma were preferentially transcribed by CD8+ T cells (40%). The results obtained by this method were in accordance with the data obtained by Northern blot analysis, with cellular protein content estimated by immuno-fluorescence staining, and with IL-2 titration by bioassay. We compared the performance of this method with ISH using radioactive probes. PMID- 7880979 TI - Murine interleukin-4 production with baculovirus: an easy and rapid method for a small scale production of functional interleukins. AB - We described a baculovirus expression system for high level production of secreted murine recombinant IL-4. We have constructed a recombinant baculovirus based on Autographa californica polyhedrosis virus, containing both a synthetic PCR-derived murine IL-4 cDNA under the control of the polyhedrin promoter and the lacZ gene under the control of the P10 promoter to allow an easy detection of recombinant virus. The baculovirus IL-4 was fully functional in biological assay and was present under two glycosylated forms in the supernatants of infected Sf9 cells. We also detected a third unglycosylated intracytoplasmic form resulting from a fusion between the 35 first amino acids of polyhedrin and the murine IL-4. Finally, confocal microscopy showed that this recombinant protein was secreted along a classical pathway like in mammalian cells. PMID- 7880980 TI - Pharmacokinetics and pharmacodynamics of furosemide after intravenous and oral administration to spontaneously hypertensive rats and DOCA-salt-induced hypertensive rats. AB - The pharmacokinetics and pharmacodynamics of furosemide were investigated after intravenous (i.v.), 1 mg/100 g body weight, and oral administration, 2 mg per 100 g body weight, to spontaneously hypertensive rats (SHRs) and deoxycorticosterone acetate-salt-induced hypertensive rats (DOCA-salt rats). After i.v. administration, the 8 h urinary excretion of furosemide/g kidney (397 versus 572 micrograms) was significantly lower and the non-renal clearance (5.78 versus 3.94 ml min-1 kg-1) was significantly faster in SHRs of 16 weeks of age than in age matched control Wistar rats. This suggested that the non-renal metabolism of furosemide could be faster in SHRs of 16 weeks of age than in age-matched control Wistar rats, and this could be supported by the significantly greater amount of 4 chloro-5-sulphamoyl anthranilic acid, a metabolite of furosemide, excreted in 8 h urine as expressed in terms of furosemide (11.1 versus 4.79% of the i.v. dose) in SHRs. It could also be supported at least in part by a study of liver homogenate; the amount of furosemide remaining per gram of liver after 30 min incubation of 50 micrograms of furosemide with the 9000g supernatant fraction of liver homogenate was significantly smaller (40.4 versus 43.7 micrograms) in SHRs of 16 weeks of age than in age-matched Wistar rats. The greater metabolic activity of furosemide in liver may also be supported by the result that the amount of hepatic cytochrome P-450 (0.7013 versus 0.5186 nmol/mg protein) and the weights of liver (3.52 versus 2.93% of body weight) were significantly greater in SHRs of 16 weeks of age than in age-matched Wistar rats. After i.v. administration of furosemide, the 8 h urine output (9.93 versus 16.5 ml) and 8 h urinary excretion of sodium (1.21 versus 2.05 mmol) and chloride (1.37 versus 2.17 mmol) per gram of kidney in SHRs of 16 weeks of age were lower than those in age-matched Wistar rats, this could be due to the significantly smaller amount of furosemide excreted in 8 h urine per gram of kidney. After oral administration, the pharmacokinetics and pharmacodynamics of furosemide were not significantly different between SHRs and the control Wistar rats of 16 weeks of age. After i.v. and oral administration of furosemide, there were no significant differences in the pharmacokinetics and pharmacodynamics between DOCA-salt rats and control SD rats of 16 weeks of age except for the significantly lower urinary excretion of potassium per gram of kidney in DOCA-salt rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7880981 TI - The effect of multiple doses of ranitidine on the pharmacokinetics and metabolism of diltiazem in dogs. AB - In order to determine the potential pharmacokinetic drug interaction between ranitidine and diltiazem (DTZ), each of ten male beagle dogs, age 2.7-4.0 years, weight 13-16 kg, received a single oral dose of sustained release DTZ with and without previous multiple oral doses of ranitidine (150 mg bid for five doses). The dog was selected as the animal model because the pharmacokinetics and metabolism profiles of DTZ are similar to those in humans and because sustained release DTZ capsules can be administered with ease to this species. Following the oral dose of DTZ, blood samples (5 ml each) were obtained via a cephalic vein at 0 (just before dosing), 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 30, 36, and 48 h after the dose. Urine samples were collected for 48 h post dose. Plasma and urine concentrations of DTZ and its major metabolites N-monodesmethyl DTZ (MA), deacetyl DTZ (M1), and deacetyl N-monodesmethyl DTZ (M2) were determined by HPLC. Pharmacokinetic parameters were calculated by non-linear curve fitting, and the effect of ranitidine was evaluated by two-factor analysis of variance (ANOVA). Pre-treatment of the animals did not significantly alter the disposition of DTZ (p > 0.05). Similar to the results reported in clinical studies, there were large variations in the plasma and urine concentrations of DTZ and its major metabolites among the beagle dogs. The effect of ranitidine on the disposition of DTZ was highly variable. PMID- 7880982 TI - Kinetic modelling of liposome degradation in serum: effect of size and concentration of liposomes in vitro. AB - The purpose of this study is to propose a new method for quantitative evaluation of liposome degradation in serum. The time course of liposome degradation in rat serum was monitored continuously, using 6(5)-carboxyfluorescein as an aqueous phase marker. The degradation curves exhibited three characteristic phases: lag time, degradation, and plateau. This curve was described by a kinetic model with three parameters: lag time (tau), first-order degradation rate constant (k), and maximum degradation (alpha). The rate and extent of the degradation of liposomes were evaluated separately in terms of k and alpha, respectively. The effects of size and concentration of liposomes on their degradation kinetics were examined using this method. Both k and alpha increased with increasing liposomal size. The increased affinity of larger liposomes for complement was suggested to increase both k and alpha. On the other hand, alpha decreased with increasing liposomal concentration without altering k. The decreased extent of degradation was considered to result from the depletion of complement components. There was no significant effect of size and concentration of liposomes on tau. Quantitative evaluation of the rate and extent of degradation of liposomes will provide deeper insights into the interaction between liposomes and serum components, and basic information on liposomes as potential drug carriers. PMID- 7880983 TI - Pharmacokinetics and pharmacodynamics of a slow-release formulation of diltiazem after the administration of a single and repeated doses to healthy volunteers. AB - Diltiazem is a calcium antagonist used in angina pectoris and hypertension. There is little information concerning the slow-release (SR) formulation in the literature. The pharmacokinetics of diltiazem SR (120 mg) have been assessed over a 36h period in healthy volunteers after single- (SD) and multiple-dose (MD) administrations. Cmax, AUC0-36, and AUC0-infinity were significantly increased at steady state compared to the extrapolated SD values, suggesting accumulation of the drug. Renal and cardiovascular parameters have also been assessed at intervals of 3-6h during baseline (B) and following single and multiple doses of diltiazem SR. Diuresis over a 24 h period was increased, but not significantly, by the administration of diltiazem SR i.e. 1782 ml (MD) and 1915 ml (SD), versus 1626 ml (B). Natriuresis and creatinine clearance were slightly decreased by diltiazem SR, compared to B values; this might be due to the relatively short period over which steady state was maintained (five days) and the effects of norepinephrine and angiotensine II on renal vasculature and the pharmacokinetics of diltiazem SR. No increase in the systolic blood pressure occurred after the administration of diltiazem SR; diastolic blood pressure and PR interval were decreased and increased respectively by diltiazem SR. These results do not appear to be clinically significant. Finally, no relation was found between the pharmacokinetics and pharmacodynamics of diltiazem. This may be attributed to the absence of clinically significant effects in healthy volunteers, the presence of active metabolites, the pharmacokinetics of the SR formulation and/or the accumulation of the drug at steady state. PMID- 7880984 TI - The effect of hepatic disease on the disposition of moricizine in humans. AB - The pharmacokinetics of moricizine and two of its metabolites, moricizine sulfoxide and phenothiazine-2-carbamic acid ethyl ester sulfoxide, were studied in healthy control subjects and in patients with chronic liver disease (cirrhosis). Moricizine disposition was significantly altered by hepatic cirrhosis. Compared to healthy subjects, the hepatic disease patients had an increased Cmax (59%), an increased t1/2 (141%), and a reduced plasma clearance (71%). Additionally, small but statistically significant increases were observed for tmax and the fraction of moricizine not bound to plasma proteins in patients with hepatic disease. The elimination of both moricizine metabolites was also altered by hepatic dysfunction as indicated by significantly prolonged terminal half-lives. Furthermore, there was a reduction in the conversion of moricizine to moricizine sulfoxide. Both hepatic blood flow and hepatic metabolizing capacity were assessed in all subjects and patients by administration of indocyanine green and antipyrine, respectively. Indocyanine green and antipyrine plasma clearances were decreased by 38 and 51%, respectively, indicating that both functions were diminished by hepatic cirrhosis. We conclude that the moricizine dose required for arrhythmia patients with hepatic disease should be lower, and perhaps, the dosing frequency should be less than in patients with normal liver function. PMID- 7880985 TI - A single-dose comparison of the bioavailability of aluminium from two formulations of sucralphate in normal volunteers. AB - The oral bioavailability of aluminium was compared after administration of 1 g sucralphate as either a tablet or a suspension (1 g/5 ml) in a crossover study in 16 healthy volunteers. Aluminium levels were detectable in all subjects pre-dose (21.4 +/- 8.8 micrograms l-1 before tablet; 21.4 +/- 7.4 micrograms l-1 before suspension) and there was a measurable increase in the plasma concentrations of aluminium in all subjects after administration of the suspension, and in 14 of the subjects after administration of the tablet formulation, with Cmax reached within the first 8 h in most subjects. Plasma levels were still elevated 72 h after dosing. The variability in plasma levels of aluminium was significantly higher after administration of the suspension (CV 39-53%) than after administration of the tablet (CV 29-44%), reflecting greater absorption of aluminium from the suspension formulation in three subjects. Similarly, the variance of the Cmax, AUC(0-72 h), and AUC(0-infinity) (for both the raw data and the baseline adjusted data) were all higher for the suspension than for the tablet. A point estimate of the difference of the pharmacokinetic parameters (determined from the median of the arithmetic Walsh averages) indicated little or no difference in Cmax, Tmax, or AUC(0-infinity) in the two formulations. In summary, the performance of the suspension formulation of sucralphate is more variable than the tablet formulation in vivo and some patients may therefore have higher circulating levels of aluminium on therapy with the suspension formulation. PMID- 7880986 TI - Post ischemic diastolic function: pursuing a cautious path from laboratory to operating room. PMID- 7880987 TI - Post-ischemic diastolic dysfunction. AB - Though a sustained post-ischemic decrease in contractile function has been clearly established, post-ischemic diastolic function has not been thoroughly investigated. Accordingly, 11 anesthetized (isoflurane 1%) open-chest beagles were instrumented to measure left ventricular pressure and dimensions (circumferential length and wall thickness) in an apicoanterior area supplied by the left anterior descending coronary artery (LAD). Pressure-dimension relations were modified by stepwise infusion and withdrawal of 200 mL of the animals' own blood during baseline, 45 minutes partial occlusion of the LAD (systolic bulging), and 60 minutes after the onset of reperfusion. Stiffness constants were derived from the end-diastolic pressure-length and stress-strain relations, respectively. Myocardial ischemia was associated with significant (P < 0.05) alterations of the following parameters of diastolic function: (1) 47% increase in end-diastolic pressure; (2) 22% decrease in peak negative dP/dt; (3) 9% increase in the time constant of isovolumic relaxation (tau); (4) postcystolic contraction; (5) 6% increase in end-diastolic length and 10% decrease in end diastolic thickness; (6) 12% increase in unstressed length (creep) and 13% decrease in unstressed thickness; (7) 51% increase in chamber stiffness and a 63% increase in myocardial stiffness; and (8) 40% decrease in the peak lengthening rate. After 60 minutes of reperfusion, only end-diastolic pressure and tau had returned to baseline values whereas systolic shortening fraction, postsystolic contraction, and end-diastolic and unstressed dimensions had only partially recovered. No recovery occurred in peak negative dP/dt, chamber stiffness, myocardial stiffness, and peak lengthening rate. Thus, both myocardial ischemia and reperfusion are associated with complex changes in global and regional left ventricular diastolic function. PMID- 7880988 TI - Effects of sevoflurane, isoflurane, enflurane, and halothane on left ventricular diastolic performance in dogs. AB - The effects of volatile anesthetics on active (ventricular relaxation) and passive (chamber stiffness) indices of diastolic function and on left ventricular filling rates in dogs were studied to determine how these agents affect left ventricular diastolic performance. Thirty-five mongrel dogs were randomly assigned to receive sevoflurane, isoflurane, enflurane, or halothane. Left ventricular pressure waveforms, phonocardiograms, and echocardiograms were recorded after administering the anesthetics at concentrations of 0% (control), 1%, 2%, and 3%. Ventricular relaxation was defined as the time constant of the decline in left ventricular pressure. Chamber stiffness was derived from the ventricular pressure-volume relationship during passive filling. Rapid filling rate, slow filling rate, and atrial filling rate were obtained from echocardiograms and phonocardiograms. No change in the time constant or in chamber stiffness was observed at any concentration of sevoflurane or isoflurane. However, the highest studied concentration of enflurane and halothane produced a significant increase in the time constant and in chamber stiffness. Rapid filling rate as well as atrial filling rate decreased significantly with the volatile anesthetics, especially with enflurane and halothane. Sevoflurane and isoflurane did not alter ventricular relaxation or chamber stiffness, but did affect diastolic function as manifested by their alteration of filling rates. In contrast, enflurane and halothane each prolonged ventricular relaxation and increased chamber stiffness. With the administration of the volatile anesthetics, the rapid filling rate decreased with the deterioration of diastolic function; in addition, atrial filling rates decreased and did not compensate for the reduction in early ventricular filling. PMID- 7880989 TI - On-line estimation of cardiac output with a new automated border detection system using transesophageal echocardiography: a preliminary comparison with thermodilution. AB - Continuous estimation of cardiac output would be extremely useful for hemodynamic monitoring of patients in the operating room and intensive care settings. A recently developed echocardiographic imaging system provides real-time automated border detection (ABD) with the ability to measure cyclic changes in cavity area, and thus calculate changes in intracavitary volumes. Eight patients undergoing cardiac surgery were studied with intraoperative transesophageal (TEE), and cardiac outputs obtained with this new imaging system were compared with thermodilution (TD). Triplicate measurements were obtained simultaneously at five intraoperative times, three before and two after cardiopulmonary bypass. The 91 of 120 measurements with adequate TEE and TD data were analyzed. The average difference between the two techniques (bias) was -0.2 +/- 1.3 L/min. The limits of agreement (bias +/- 2 SD) were -2.8 L/min to 2.4 L/min. The average of the absolute value of the difference between measurements made with the two techniques was 0.9 +/- 0.8 L/min. Linear regression yielded the equation: ABD = 0.64TD + 1.57 L/min (r = 0.71). The average difference between the two techniques (bias) for detecting changes in cardiac output between sequential intraoperative times was 0.1 +/- 1.1 L/min. With further development, this new method shows promise for measurement of cardiac output in selected patient care settings. PMID- 7880990 TI - Comparison of cardiac output measurement by continuous thermodilution with electromagnetometry in adult cardiac surgical patients. AB - A pulmonary artery catheter (PAC) capable of continuous cardiac output (CCO) determination by thermodilution has recently been introduced. The purpose of this study was to compare CCO with two other methods of cardiac output (Ot) determination: electromagnetometry (EM) and standard bolus thermodilution cardiac output (BCO). Following median sternotomy and pericardiotomy, an EM ring probe was placed around the ascending aorta in 25 adult cardiac surgical patients and connected to an EM flowmeter interfaced with a calibrated strip recorder. Measurements were obtained over a 15- to 20-minute interval during a period of stable EM-determined Ot prior to initiation of cardiopulmonary bypass and in the absence of surgical stimulation. The CCO system averages Ot over a 3-minute interval, updating the measurement every 30 seconds. Cardiac output determined by the CCO system was compared with EM Ot averaged from the prior 3-minute period and with BCO obtained immediately after changing the Ot monitor from the continuous to bolus mode. Compared with EM, the bias for CCO was -0.48 L/min, precision 0.56 L/min, and the limits of agreement 1.12 L/min. Bias, precision, and limits of agreement of CCO compared with BCO were 0.41, 0.82, 1.64 L/min, respectively. Correlation between EM and CCO was r = 0.80 and between CCO and BCO r = 0.64. Cardiac output determined by CCO was within 10% of the EM determination for 37 measurements, between 10% and 20% for 17, and greater than 20% for 7 measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880991 TI - Application of a transpulmonary double indicator dilution method for postoperative assessment of cardiac index, pulmonary vascular resistance index, and extravascular lung water in children undergoing total cavo-pulmonary anastomosis: preliminary results in six patients. AB - Total cavo-pulmonary anastomosis (TCPA) is used for the functional correction of an increasing spectrum of congenital heart diseases. The passive pulmonary perfusion after surgical exclusion of the right ventricle has significant implications for the postoperative hemodynamic management of these patients. Because conventional pulmonary artery thermodilution catheters present methodologic problems in patients after TCPA, important cardiovascular variables such as cardiac index (CI) and pulmonary and systemic vascular resistance indices (PVRI, SVRI) usually cannot be assessed directly. In a preliminary series of six patients undergoing TCPA (age 6-22 years), the applicability of a transpulmonary double indicator dilution technique for postoperative determinations of CI, PVRI, SVRI, and extravascular lung water (EVLW) was investigated. After central venous injection of ice-cold indocyanine green (5 mg), thermal and dye dilution curves were recorded in the abdominal aorta using a combined 4F fiberoptic thermistor catheter. Qualitative assessment of the tracer curves did not show major differences in measurements in patients with pulsatile perfusion of the lungs. CI, SVRI, and EVLW could be determined by use of standard algorithms. Pulmonary perfusion pressure for the calculation of PVRI was based on the gradient between central venous and left atrial pressure. The quality of indicator dilution curves allowed determination of flow-related variables in 33 of a total of 34 sets of measurements. No catheter-related problems occurred during or after the period of investigation. Postoperative EVLW was within the range that is commonly accepted as normal for adults. Mean PVRI initially decreased during the postoperative course but showed a significant increase after extubation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880992 TI - Oxygen consumption following pediatric cardiac surgery. AB - Metabolic responses during recovery from cardiac operations for various congenital heart defects were studied in 30 mechanically ventilated pediatric patients in two groups: infants 1 year or less (group I) and children more than 1 year old (group II). Oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured using a pediatric metabolic monitor intermittently after induction of anesthesia, after skin closure, 2 to 4 hours postoperatively, and on the first postoperative morning in the pediatric intensive care unit. Energy expenditure and respiratory quotient were determined from respiratory gas measurements. Rectal and skin temperatures and hemodynamic variables were recorded at the same time. VO2 increased during rewarming 2 to 4 hours after the operation by 12 +/- 15% in group I and by 24 +/- 19% in group II, while rectal temperature increased by 2.0 +/- 1.2 degrees C and 1.8 +/- 1.4 degrees C, respectively. No further increase in VO2 occurred until the first postoperative morning. A hypermetabolic response was not seen in all cases despite marked thermal changes. High-dose fentanyl anesthesia partly explains the low responses. On the other hand, low cardiac output may also compromise oxygen supply. Sixty three percent of infants were treated for cardiac failure before surgery and 75% needed inotropic support immediately after the operation. Low central venous oxyhemoglobin saturation values (ScvO2 < 60%) were observed during rewarming, indicating an increase in oxygen extraction secondary to an increased oxygen demand in the brain during recovery from anesthesia, and a low cardiac output or delayed restoration of cerebral blood flow after CPB and deep hypothermia. PMID- 7880993 TI - The effects of carbon dioxide management on plasma levels of fentanyl and sufentanil during hypothermic cardiopulmonary bypass. AB - This study examined the effects of carbon dioxide (CO2) management on the plasma levels of sufentanil and fentanyl during hypothermic cardiopulmonary bypass (HCPB). Thirty-two patients undergoing elective coronary artery bypass were divided into four groups: (I) fentanyl/alpha-stat; (II) fentanyl/pH-stat; (III) sufentanil/alpha-stat; and (IV) sufentanil/pH-stat. Fentanyl was administered intravenously at 50 micrograms/kg on induction with an additional 25 micrograms/kg just prior to sternotomy. Sufentanil was administered intravenously at 7 micrograms/kg on induction with an additional 3 micrograms/kg just prior to sternotomy. Samples were drawn at 5 (A) and 30 (B) minutes after institution of CPB (25 degrees C), and at 5 (C) minutes after discontinuation of CPB. Statistical comparisons were made between Group I and II, and Group III and IV at all three measurement points. The only significant (P < .01) finding was between Group III and IV at point B. The measured plasma levels of sufentanil were significantly lower under HCPB pH-stat management conditions. Until this observation is either confirmed or refuted, it would seem prudent for studies that report the plasma levels of sufentanil during HCPB to specify the type of CO2 management used. PMID- 7880994 TI - Filtration of fentanyl is not the cause of the elevation of arterial blood pressure associated with post-bypass ultrafiltration in children. AB - Modified ultrafiltration after cardiopulmonary bypass in children has been shown to be associated with an increase in arterial blood pressure. As part of a series of studies to investigate the possible causes of this blood pressure elevation, the hypothesis that if filtration was removing a significant amount of fentanyl, then the increase in blood pressure might be due to pain was proposed. Ten children, aged between 0.5 and 9.3 years (median 3.8 years), weighing 5.9 to 25.5 kg (median 15.7 kg), underwent corrective cardiac surgery (incorporating modified ultrafiltration). A standard anesthetic protocol was followed, with up to 78 micrograms/kg of fentanyl given prebypass for analgesia. After completion of cardiopulmonary bypass, modified ultrafiltration was commenced at 100 mL/min until a hematocrit of 35% was reached. Samples were taken of arterial blood (prefiltration, 3, 10, and 20 minutes postfiltration), the venous reservoir blood (prefiltration) and the filtrate (5 and 10 minutes into filtration). Hemodynamic data were recorded both prefiltration and postfiltration. The hemodynamic data showed the expected rise in both systemic arterial pressure and cardiac index after ultrafiltration. The plasma fentanyl concentrations did not significantly change after ultrafiltration: 1.59 to 12.39 ng/mL (median 6.27 ng/mL) prefiltration and 2.05 to 15.59 ng/mL (6.29 ng/mL) at 3 minutes, 2.22 to 12.64 ng/mL (6.87 ng/mL) at 10 minutes, and 1.83 to 11.52 ng/mL (5.85 ng/mL) at 20 minutes postfiltration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880995 TI - Methemoglobin levels during prolonged combined nitroglycerin and sodium nitroprusside infusions in infants after cardiac surgery. AB - Nitroglycerin (NTG) and sodium nitroprusside (SNP) are routinely used perioperatively in infants with congenital heart defects. In this study, NTG and SNP were infused in the operating room to increase venous capacitance, reduce systemic and pulmonary afterload, facilitate weaning off cardiopulmonary bypass, stabilize hemodynamics for transport to the intensive care unit (ICU), and reduce the fluid resuscitation needed upon arrival in the ICU. Because of the risk for accumulation of methemoglobin (MetHb) and cyanmethemoglobin (cyan-MetHb) during prolonged continuous infusion of NTG and SNP, it was decided to (1) quantify ICU use, (2) measure % MetHb at 12-hour intervals, and (3) look indirectly for the accumulation of cyan-MetHb by comparing simultaneous pulse oximetry (SpO2) (Nellcor N-100 [Nellcor, Haywood, CO]) and CO-oximetry (SaO2) (Corning 270 [Corning, Medfield, MA]). A total of 69 arterial samples were obtained from 16 infants (median age 4.4 months) following cardiac surgery with bypass. Median doses of NTG, 6.0 mg/kg (range 0.7 to 27.5), and SNP, 3.3 mg/kg (range 0.6 to 33.4), were infused over a median of 64.5 hours (range 12 to 183) (N = 16 patients). The median MetHb was 0.6% (range 0.0 to 1.5) after infusions of NTG, 1.8 micrograms/kg/min (range 0.5 to 4), and SNP, 1.3 micrograms/kg/min (range 0.3 to 8.4) (N = 69 measurements). Regression analysis of oximetry data yielded the equation: SpO2 = 1.04 SaO2 - 3.7%, r = 0.97. The mean difference between SpO2 and SaO2 data pairs was 0.0% (bias) with a SD (precision) of +/- 2.3%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7880996 TI - A safer technique of internal jugular venipuncture: experience with 320 cases. AB - Placement of central venous catheters for monitoring or long-term access has become an indispensable surgical procedure. Various routes to establish central venous access have previously been described. The internal jugular vein can be cannulated percutaneously from several access points, using the clavicle and the sternocleidomastoid muscle as reference landmarks. An alternate method of internal jugular venipuncture using a previously undescribed point of entry is described. Experience with this modified technique in 320 cases where it was used for various purposes is reviewed. The incidence of complication was less than 1% and the improved safety of the procedure is attributed to the vertical direct method of venipuncture through the new access point. PMID- 7880997 TI - Continuous cardiac output measurements. PMID- 7880998 TI - Mixed venous oxygen saturation during lung transplantation. PMID- 7880999 TI - Behavior of a respiratory rate-responsive pacemaker during and after cardiac surgery. PMID- 7881001 TI - Mediastinal "tamponade" of a tracheal rupture in which partial cardiopulmonary bypass was required for surgical repair. PMID- 7881000 TI - Primary pulmonary hypertension: prolonged cardiac arrest and successful resuscitation following induction of anesthesia for heart-lung transplantation. PMID- 7881002 TI - The use of microfiltration in cardiopulmonary bypass. PMID- 7881003 TI - Case 6--1994. Video-assisted thorascopic surgery using a single-lumen tube in spontaneously ventilating anesthetized patients: an alternative anesthetic technique. PMID- 7881004 TI - Localized outpouching of the descending thoracic aorta. PMID- 7881005 TI - Give credit where credit is due: the funny capnograph. PMID- 7881006 TI - Crystalloid versus blood cardioplegia. PMID- 7881007 TI - Calculating the required amount of cardiovascular drugs in syringe pumps for pediatric cases: "formula of 3"--a simple method. PMID- 7881008 TI - Accidental fracture of arterial luer line during CPB. PMID- 7881009 TI - International Symposium on Peptic Ulcer, from Experimental Approaches to Clinical Uses. Hong Kong, 8-10 January 1994. PMID- 7881010 TI - How Helicobacter pylori acquired its name, and how it overcomes gastric defence mechanisms. AB - At Royal Perth Hospital, Western Australia in April 1982, spiral bacteria were first cultured from a gastric biopsy specimen. Several important taxonomic features were identified which indicated that these bacteria represented a new genus. In October 1989 the new genus name Helicobacter was published. Helicobacter pylori overcomes gastric defence mechanisms by means of its powerful urease enzyme, by its spiral shape allowing it to penetrate mucus, by adherence to the gastric mucosa and by various mechanisms which enable it to evade the immune response. PMID- 7881011 TI - Gastric mucosal defensive factors: the therapeutic strategy. AB - There are several interesting approaches to augmenting defence or repair mechanisms that can be used already or may find a place in therapy for ulcer disease. Factors such as epidermal growth factor and basic fibroblast growth factor show potential. Alternative strategies might be to stimulate mucosal blood flow with agents that release nitric oxide (NO), or to scavenge free radicals in the inflamed or ischaemic mucosa. If such approaches are to find a role in therapy, it is likely that it will be restricted: perhaps for the treatment of refractory ulcers, or for prophylaxis of stress ulceration. This is because most ulcers in future are likely to be healed with tolerable and high efficacy acid inhibiting drugs then have their recurrence prevented by regimens that eradicate Helicobacter pylori. The most important current indication for concentrating on enhancing mucosal defences is for managing non-steroidal anti-inflammatory drug (NSAID)-induced ulcers. There is no clear advantage in using a defence-enhancing agent (rather than an acid suppressant) to heal an NSAID ulcer if the NSAID can be stopped. The main value of prostaglandins is for prophylaxis of NSAID ulcers in those patients who need ongoing treatment with NSAID. For cost-benefit reasons, prostaglandins should probably be used mainly for those at high risk of NSAID complications, and there has been progress in identifying these. Another interesting approach is aimed at clarifying mechanisms of gastric adaptation to NSAID, so that we might be able to design drugs and dosing regimens to maximize this phenomenon. PMID- 7881012 TI - The therapeutic strategy for peptic ulcer disease. AB - Therapy of acid/peptic disease has evolved since the 1970s with development of: (i) more accurate endoscopes which permit precise examination and documentation of upper gastrointestinal lesions; and (ii) the histamine H2-receptor antagonists. As well, refined standards for clinical investigation have contributed to the clinical study of acid/peptide diseases. Initially, ulcer diseases were considered to be principally secondary to increased 'aggressive' factors (acid, pepsin) and the therapeutic focus was directed at antacids, the progressive evolution of additional histamine H2-receptor antagonists and recently the H+/K(+)-ATPase inhibitors. Later studies indicated efficacy of sucralfate, low dose antacids and prostaglandin analogues, drugs with either no or only modest antisecretory effect. This led to studies on the role of gastroduodenal mucosal defensive factors (mucus and bicarbonate secretion, blood flow, leucocyte adherence, cytokines, reactive oxygen radicals). The prominent role played by aspirin and other non-steroidal anti-inflammatory drugs (NSAID) in initiating and causing recurrence of peptic ulcer disease has been increasingly realized. Recognition of those most at risk for NSAID-induced complication has led to newer approaches to treatment and prevention. Since 1983, Helicobacter pylori has been incriminated as a major factor in the pathogenesis of ulcer disease, particularly ulcer recurrences. Treatment of such ulcers now includes antibiotics and bismuth compounds in order to eradicate H. pylori. This therapeutic regimen is in a state of flux ('triple therapy' vs a H+/K(+)-ATPase inhibitor plus antibiotic) as is the question of how to work up and treat patients initially presenting with ulcer symptoms. PMID- 7881013 TI - Effect of ammonium ion on the hydrophobic and barrier properties of the gastric mucus gel layer: implications on the role of ammonium in H. pylori-induced gastritis. AB - Infection with the bacterium Helicobacter pylori is associated with both the development of gastritis and an attenuation in the hydrophobic properties of the stomach. In order to better understand the effect of ammonium, one of the major products of H. pylori urease on these properties, a series of in vivo and in vitro experiments was performed. In the in vivo studies rats were intragastrically administered NH4Cl alone and in combination with the mucolytic agent, Muco-Mist, in various dosing strategies and concentrations. It was determined that the intragastric administration of four consecutive doses of a NH4Cl/Muco-Mist mixture (20 mmol/L/5%) was capable of converting the stomach from a hydrophobic to hydrophilic state as determined by contact angle analysis. Further, the treated rats became more susceptible to the injurious effect of luminal acid as determined by measuring the haemoglobin concentration of a collected gastric perfusate. In the in vitro studies it was determined that exposure of the hydrophobic surface of a synthetic mucus gel layer to increasing concentrations of NH4Cl (0-20 mmol/L) resulted in a rapid transition to a hydrophilic state and an associated increase in the flux of H+ across its surface. Helicobacter pylori may induce an attenuation in both mucosal hydrophobicity and barrier properties by producing high concentrations of NH4+ in the mucus gel layer. The molecular mechanism of this action may be related to the chemical similarities of NH4+ and choline-based phospholipids which contribute to the stomach's hydrophobic surface. PMID- 7881014 TI - Peptic ulcer in hepatic cirrhosis and renal failure. AB - The prevalence of peptic ulcer in cirrhotic patients is similar to that reported for the general population. Although gastric acid outputs ar normal or lower in cirrhotic subjects compared with non-cirrhotics, the frequency of non-response to histamine H2-receptor antagonists is higher. Peptic ulcer disease in the cirrhotic seems to pursue a more virulent course compared with that in the non cirrhotic subject. Peptic ulcer prevalences in patients dying of uraemia or in uraemic patients on maintenance dialysis treatment are comparable with those in the general population. However, the frequency of peptic ulcer, especially complicated ulcer, is increased following renal transplantation. Ulcer complications in this context are associated with a high mortality rate. Pre transplant risk factors for subsequent development of peptic ulcer remain to be identified and the value of histamine H2-receptor antagonists in prophylaxis is as yet unproven. PMID- 7881015 TI - Intracisternal thyrotropin-releasing hormone-induced vagally mediated gastric protection against ethanol lesions: central and peripheral mechanisms. AB - The vagus is involved in mediating gastric cytoprotection and adaptive cytoprotection. However, the central and peripheral mechanisms through which the vagus expresses its action are still poorly known. Medullary thyrotropin releasing hormone (TRH) plays an important role in the vagal regulation of gastric function. The stable TRH analogue, RX 77368, micro-injected into the cisterna magna or the dorsal motor nucleus (DMN) of the vagus at a dose that did not influence gastric acid secretion prevented gastric injury induced by intragastric administration of 60% ethanol in conscious or urethane-anaesthetized rats. The cytoprotective action of TRH is mediated through vagal cholinergic release of prostaglandin E2 (PGE2). Prostaglandin E2 action is unrelated to changes in gastric mucosal blood flow (GMBF). In addition, other peripheral mechanisms involve calcitonin gene-related peptide (CGRP) contained in capsaicin sensitive afferent fibres and nitric oxide, both of which mediate the associated increase in GMBF induced by intracisternal injection of RX 77368. These data indicate that medullary TRH induces vagally mediated gastric protection against ethanol lesions. Its action is expressed through the muscarinic dependent release of PGE2 and nitric oxide, and efferent function of capsaicin-sensitive afferent fibres releasing CGRP. PMID- 7881016 TI - Central nervous system and gut interactions: dopamine and experimental gastroduodenal lesions. AB - There is increasing evidence for brain regulation of gastroduodenal function and pathological responses. This laboratory has demonstrated a significant role for dopamine (DA) as a modulator of gastrointestinal function and disease. Using models of both acute (ethanol restraint stress; cysteamine) and chronic (iodoacetamide-induced gastritis) gastroduodenal mucosal injury, as well as tests of gastric secretory function (conscious basal gastric acid secretion; pylorus ligation; ex vivo gastric chamber), we have shown that DA, particularly DA1/D1 receptor agonists are powerful gastroprotective agents. This action is demonstrable upon peripheral administration as well as central (particularly intramesolimbic) administration. DA1/D1 agonists such as SKF38393 and SKF75670C reduce experimental gastric mucosal injury and secretion while antagonists of these receptors, including SCH23390, worsen experimental gastroduodenal lesions and augment secretion. That there exists a significant central component to DA induced gastroprotection is demonstrated by data showing that rats assessed as anxiety prone, develop a greater degree of experimentally induced gastric damage, require greater amounts of DA agonists for 50% gastroprotection and respond to exogenous stress challenge with greater central DA turnover and loss, relative to rats assessed as low in anxiety. Very recently, we showed that dopamine D4 receptor blockade by clozapine and activation of dopamine D3 receptors by 7 hydroxy-N, N-di-n-propyl-2-aminotetralin (7-OHDPAT) are also associated with antiscretory and gastroprotective effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881017 TI - Helicobacter pylori epidemiology in relation to peptic ulcer and gastric cancer in south and north China. AB - Peptic ulcer disease is twice as common in people living in South China when compared with those in North China. However, the gastric cancer rate in North China is three times that of South China. The overall Helicobacter pylori prevalence rate is similar in North and South China populations and it is higher than Caucasians living in Western societies. However, there is a significantly higher prevalence of H. pylori seropositivity among those who live in the high gastric cancer areas of China. On the other hand, there is no significant difference in the H. pylori positive rate in the peptic ulcer disease patients between the two regions of China. Other permissive/associated co-factors in the development of peptic ulcer disease or gastric cancer remain unknown at this stage. PMID- 7881018 TI - Nitric oxide-releasing non-steroidal anti-inflammatory drugs: a novel approach for reducing gastrointestinal toxicity. AB - The use of non-steroidal anti-inflammatory drugs (NSAID) for treatment of inflammatory conditions is significantly limited by the untoward effects of these compounds on the gastrointestinal tract. While the pathogenesis of 'NSAID gastropathy' is not completely understood, there is good evidence that the process is directly linked to suppression of prostaglandin synthesis and possibly to neutrophil adherence to the vascular endothelium. Pretreatment of rats with a nitric oxide (NO) donor (sodium nitroprusside) was found to significantly reduce the extent of gastric injury induced by flurbiprofen. We therefore tested the effects of a novel derivative of flurbiprofen. This compound contains a moiety similar to the NO-releasing moieties found in many organic nitrates. This compound suppressed gastric prostaglandin synthesis as effectively as flurbiprofen, but caused significantly less haemorrhagic damage. The compound was also found not to induce small intestinal injury. Since the compound was found to exert anti-inflammatory effects comparable with flurbiprofen, NO-releasing NSAID may represent a novel class of drugs with markedly reduced gastrointestinal toxicity. PMID- 7881019 TI - Involvement of endogenous nitric oxide in the inhibition by endotoxin and interleukin-1 beta of gastric acid secretion. AB - Administration of Escherichia coli endotoxin abolished the acid secretory response induced by a bolus injection of pentagastrin in the continuously perfused stomach of the anaesthetized rat. Likewise, acid secretion stimulated by the continuous intravenous perfusion of pentagastrin was inhibited by administration of interleukin-1 beta (IL-1 beta). In both cases pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) but not dexamethasone or indomethacin substantially restored the secretory responses to pentagastrin. The actions of L NAME were reversed by the prior administration of L-arginine but not by its enantiomer D-arginine. Even though L-NAME increased blood pressure, this does not seem to be the mechanism by which endotoxin-induced acid inhibition was prevented, since similar systemic pressor responses induced by phenylephrine had no such effect. The secretory response elicited by pentagastrin in the isolated lumen perfused stomach of the rat was not influenced by incubation (100 min) with IL-1 beta. These observations suggest that the acute inhibition of acid responses to pentagastrin by endotoxin and IL-1 beta involves nitric oxide (NO) synthesis from L-arginine. PMID- 7881020 TI - The gastroduodenal mucus barrier and its role in protection against luminal pepsins: the effect of 16,16 dimethyl prostaglandin E2, carbopol-polyacrylate, sucralfate and bismuth subsalicylate. AB - Mucus and bicarbonate secretions have been widely implicated as an important pre epithelial protective barrier against autodigestion of the gastric mucosa by acid and pepsin. Evidence from several independent studies shows there is a continuous layer of resilient viscoelastic mucus gel adherent to the surface of the gastroduodenal mucosa. The median thickness of the adherent gastric mucus layer in humans is 180 microns, range 50-450 microns. The epithelial bicarbonate secretion permeates the unstirred matrix of mucus gel neutralizing luminal acid and establishing a pH gradient within the gel. In the duodenum, evidence supports the mucus bicarbonate barrier as a major protective mechanism against acid aggression. The adherent mucus gel, by acting as an effective 'permeability' barrier to pepsin, protects the underlying sensitive mucosa from digestion. However, pepsin slowly digests mucus gel at its luminal surface to produce soluble degraded mucin. In a rat gastric damage model in vivo, pepsin in excess digests the gastric mucus barrier sufficiently rapidly to outweigh new mucus secretion and lead to breaching of the mucus barrier with the formation of small punctate ulcers in the epithelium accompanied by mucosal haemorrhage. The mucus secretagogue 16,16 dimethyl prostaglandin E2 and the muco-adhesive carbopol polyacrylate both fully protected the mucosa against pepsin damage by enhancing the protective properties of the mucus barrier. Sucralfate and bismuth subsalicylate were partially effective in protection against pepsin damage but this protection was mainly mediated at the level of the mucosa. In peptic ulcer disease, there is increased mucolytic (mucus degrading) activity in gastric juice and this is associated with an impaired mucin polymeric structure and a weaker mucus barrier.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881021 TI - Validity of kissing gastric ulcers induced in rats for screening of antiulcer drugs. AB - We examined the validity of kissing gastric ulcers induced in rats by determining the effects of conventional antiulcer drugs. Gastric ulcers were produced by luminal application of 60% acetic acid (0.2 mL, 45 s) to an area clamped with a pair of forceps. The ulcers were evaluated as to either the ulcerated area (mm2) or ulcer index (ulcerated area x depth). The healing of kissing ulcers was significantly enhanced by 2 week treatment with oral omeprazole (10, 30 mg/kg per day), leminoprazole (30, 60 mg/kg per day) or cimetidine (300, 450 mg/kg per day). The rate of healing was > 50% to both the ulcerated area and ulcer index. Aluminium hydroxide (up to 1800 mg/kg per day) had no effect on ulcer healing on the ulcerated area, but it caused a significant reduction in the ulcer index. Gastric acid secretion was significantly inhibited by repeated administration of omeprazole, leminoprazole and cimetidine in a dose-dependent manner. Aluminium hydroxide significantly increased the pH of the gastric contents. The mechanism of action of these drugs appears to involve partly the inhibition of gastric acid secretion and neutralization of secreted acid. We conclude that kissing gastric ulcers are a sensitive ulcer model for the screening of antiulcer drugs. PMID- 7881022 TI - Effect of nicotine in migration and proliferation of rabbit gastric mucosal cells in a culture cell model. AB - The aim of this study was to assess the effects of nicotine on the gastric epithelial restoration using primary cultured rabbit gastric mucosal cell model. Confluent monolayer mucosal cell sheets consisting of mainly mucous cells were wounded using a rotating silicon tip. The process of restoration was monitored, and the size of wound was measured and analysed quantitatively. Artificial wounds recovered in 36 h in controls. The nicotine treatment (10(-5), 10(-4) and 10(-3) mol/L) did not cause any effects on the process of wound repair. Bromodeoxyuridine (BrdU) positive cells appeared around the wound 24-36 h after injury and then disappeared after the complete repair in controls and also in nicotine-treated groups. However, in the morphological observation, numerous vacuoles were detected in parietal cells of nicotine-treated groups. This effect of nicotine was reversible by removing nicotine from the medium. Present data suggest that nicotine has no direct effects on the mucosal restoration but might have an effect on the structure and function of parietal cells. PMID- 7881023 TI - Extracellular matrix constituents affect superficial gastric epithelial cell adhesion. AB - The interfoveolar and upper gastric pit cells become necrotic and slough off after superficial luminal injury to the gastric mucosa. The subsequent rapid epithelial restitution of the wound is dependent on an intact basal lamina upon which viable mucous cells migrate. Several lines of evidence suggest that migrating mucous cells recognize specific moieties in the basal lamina which would then affect restitution and the ability of the gastric mucosa to be repaired. Therefore, this study examined the effect of three individual protein constituents of the extracellular matrix, laminin, fibronectin and type IV collagen as well as a synthetic basal lamina, Matrigel, on adherence of mucous cells isolated from guinea-pig stomach to these substrates in culture. After 3 h, approximately 40% of the cells adhered to Matrigel, 25% to both collagen IV and fibronectin, but only about 10% to laminin and 3% to uncoated plastic substrates. Disruption of protein synthesis by pre-incubation with cyclohexamide significantly reduced adherence to Matrigel and collagen IV but not laminin, fibronectin or plastic substrates. These results suggest that gastric mucous cells have multiple receptors for extracellular matrix proteins (ligands) which influence the adherence and probably the migration of these cells. Furthermore, some of these receptors are synthesized in response to moieties in the substrate itself. PMID- 7881024 TI - Gastric ulcer treatment with intravenous human epidermal growth factor: a double blind controlled clinical study. AB - We introduced a double-blind controlled clinical study to compare intravenous human epidermal growth factor (hEGF) to cetraxate hydrochloride (CH), an antiulcer drug, for their healing effect on gastric ulcers. We also prospected an oral use of EGF on the basis of our experimental evidence. In the clinical trial, the rate of ulcer healing within 8 weeks was 77.9% (67/86) in patients receiving 6 micrograms EGF intravenously twice a week, being significantly greater than 51.7% (45/87) in those given CH. Taking together all aspects assessed including the healing rate, pain relief, blood examination and adverse reactions, we judged the hEGF to be a useful and safe anticuler drug. In rats, 50 micrograms/kg mouse EGF (mEGF) and 2% hydroxypropyl cellulose (HPC) or 1.0 g/kg sucralfate given by gastric intubation significantly raised the residual mEGF levels in both gastric luminal content (HPC: x 30; sucralfate: x 300 as high as those in EGF alone) and tissue (HPC: x 60; sucralfate: x 100). In addition, the combined treatments significantly promoted healing of rat gastric ulcers whereas each agent alone had no significant effect as compared with control (saline). This indicated the beneficial effect on ulcers of oral administration of EGF with agents allowing it to remain at high levels in the stomach, whereas most reports suggested less effect of oral EGF on healing of gastroduodenal ulcers. Subsequent to the clinical study, evaluation of oral use of EGF may be expected as the next step in the treatment of ulcers. The experimental evidence above would possibly be a guide for such trial. PMID- 7881025 TI - How does Helicobacter pylori cause duodenal ulcer disease: the bug, the host, or both? AB - Helicobacter pylori infection is the most common cause of duodenal ulcer disease, yet duodenal ulcer is an uncommon outcome of H. pylori infection. We reviewed the possible explanations such as differences in the host or in the strain of H. pylori. Host factors reviewed included genetic susceptibility to H. pylori infection and excess gastric acid secretion. The role of potential H. pylori virulence factors not present in all strains such as the cagA gene and the results of other molecular methods to identify disease-specific differences among isolates was also reviewed. Although cure of H. pylori infection resolves gastrin releasing peptide stimulated acid secretion there was no change in parietal cell mass. Twin studies have shown genetic differences in H. pylori susceptibility. There was no difference in the prevalence of the cagA gene between H. pylori infected asymptomatic volunteers and duodenal ulcer patients (P = 1.0). DNA-DNA hybridization of whole genomic DNA in solution and cluster analysis of rep-PCR genomic DNA fingerprints suggest that isolates from patients with duodenal ulcer disease are different from those obtained from individuals with asymptomatic gastritis. Cluster analysis of the rep-PCR DNA fingerprints revealed two major groups of the strains; one set consisted of strains from patients with duodenal ulcer disease and the second cluster consisted largely of strains from individuals with asymptomatic gastritis. Recent molecular studies suggest that disease-specific cell lineages or strains may exist among H. pylori isolates leading to the various outcomes observed in patients with H. pylori infection. PMID- 7881026 TI - Histological maturity of healed duodenal ulcer and ulcer recurrence after treatment with omeprazole or cimetidine. AB - We investigated the relationship between histological maturity of healed duodenal ulcer and ulcer recurrence after treatment with omeprazole or cimetidine for 4 weeks. The healing rates, 92.5 and 72.4% in omeprazole-treated and cimetidine treated groups, respectively, showed no significant difference between groups (P > 0.05). Histologically, the regenerating mucosa of healed ulcer was divided into three categories: good, fair and poor patterns. Of the healed cases, 22 (59.5%) of 37 omeprazole-treated and 12 omeprazole-treated and 12 (28.6%) of 42 cimetidine-treated ulcers achieved a good pattern, showing significant difference between groups (P = 0.01). The recurrence rate at 3 months showed statistically significant difference (P < 0.05) between two groups: 5.4% in omeprazole-treated and 23.8% in cimetidine-treated patients. During the period between 3 and 6 months after healing, the difference in recurrence rate between omeprazole treated and cimetidine-treated groups was statistically not significant (12.5% and 25%, respectively, P > 0.05), though the cumulative recurrence rate at 6 months showed a significant difference between groups (17.6% vs 44.7%, P = 0.027). All the recurrent cases of both groups had a fair or poor pattern of regenerating mucosa. The difference in recurrence rate was statistically significant between the healed ulcers with a good pattern and that with a fair or poor patterns both at 3 months and between 3 and 6 months after healing (P < 0.001 in each). We concluded that better histological maturity of regenerating mucosa may contribute to the lower early recurrence in omeprazole-treated cases than in cimetidine-treated cases. PMID- 7881027 TI - Dynamism of cytoprotective and antisecretory drugs in patients with unhealed gastric and duodenal ulcers. AB - A continuous multiclinical, randomized and prospective study has been carried out in our department to compare the efficacy of different cytoprotective (sucralfate, DE-NOL, Vitamin A) and antisecretory drugs (atropine, cimetidine, ranitidine, famotidine, pirenzepine) on ulcer healing in patients with chronic gastric ulcer (GU) and duodenal ulcer (DU). A total of 441 patients were randomized in different groups. The patients were treated with atropine (1 mg/day), cimetidine (1000 mg/day), ranitidine (300 mg/day), famotidine (80 mg/day), pirenzepine (50 mg/day), sucralfate (1000 mg/day), Vitamin A (3 x 50,000 IU/day) alone or in combination with cyproheptadinum (3 x 4 mg/day) DE-NOL (3 x 5 mL/day) and Tisacid (Al-Mg-hydroxycarbonicum; in different doses). Endoscopy (planimetric evaluation of ulcer sizes), measurements of clinical changes in patients' complaints, antacid consumption and laboratory tests (blood counts, urine, kidney and liver functions, electrolytes, pH status) were carried out at the beginning and 2, 4 and 6 weeks after treatment with different drugs. The incidence of ulcers, changes of ulcer sizes, subjective pain score and antacid consumption were noted at the abovementioned times. There were 20 or more patients in each group. The dynamism of ulcer healing rate was studied on the unhealed GU and DU. Our results showed that the ulcer size decreased significantly in all groups in GU and DU patients treated with cytoprotective and antisecretory drugs. Summed pain score (expressed as per cent of basic values) and antacid consumption decreased significantly in all groups. As well, some differences were found in the dynamism of ulcer healing at 2 weeks after the treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881028 TI - Aetiological factors of peptic ulcer: perspectives of epidemiological observations this century. AB - There are five known environmental, causative factors for peptic ulcer, namely, non-steroidal anti-inflammatory drugs (NSAID), Helicobacter pylori infection, cigarette smoking, environmental stress and dietary habit. There have been six factual, epidemiological observations on peptic ulcer this century: the rise and fall of ulcer frequency in Western societies; geographical variations in ulcer rates; in sex ratios; in duodenal: gastric ulcer ratios; and in placebo healing rates; and seasonal variation in ulcer frequencies. This report examines each of these epidemiological observations to see if each of the environmental factors can explain the observations. The secular trends and the variation in ulcer rates can be related to all the environmental factors. The sex ratios can be explained on the basis of cigarette smoking and environmental stress, whereas the duodenal: gastric ulcer ratios may be ascribed to NSAID use. Placebo healing and seasonal occurrence of ulcer is probably more related to environmental stress. Helicobacter pylori infection alone cannot explain the sex ratios, the duodenal: gastric ulcer ratios, the placebo healing and the seasonal occurrence of ulcer. Cigarette smoking or NSAID use alone does not tally with the seasonal variation of ulcer frequencies. Environmental stress alone does not fit into the recent fall of ulcer rates in Western countries. This report supports the concept of heterogeneity in peptic ulceration. PMID- 7881029 TI - Clinical relevance of basic research in peptic ulcer disease. AB - Historically, the interplay between basic research and clinical observation has been essential in the development of new therapies for peptic ulcer disease. That histamine is an important regulator of acid secretion emerged from basic research, followed by the clinical development and use of the H2-receptor antagonists. Basic research contributed again by defining the importance of H+/K(+)-ATPase in acid secretion, resulting in a new class of useful antisecretory agents. Basic studies also gave us prostaglandins (PG) as mucosal protective agents. As 'replacement' therapy, clinicians have found that PG are protective against non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcer (GU). Physiologic studies established that somatostatin is a potent inhibitor of acid secretion, providing the stimulus for clinical studies in Zollinger-Ellison (ZE) Syndrome with a synthetic analog (octreotide). Work on isoforms of the parietal cell gastrin receptor has shown differences in the cytoplasmic domain for G protein coupling. This will aid in understanding how receptor changes and coupling to second messengers relate to the aetiopathogenesis of abnormal gastric secretion. Immune cells express mRNA for histamine, muscarinic and gastrin receptors, supporting the relevance of mucosal immunology in gastroenterology, especially in light of Helicobacter pylori associated gastritis and ulcers. Lab research has revealed a potential role for basic fibroblast growth factor (bFGF), and another endogenous peptide BPC-15, in ulcer healing. The former substance may be responsible for the antiulcer efficacy of sucralfate. Intensive basic work on how H. pylori organisms attach to gastric cells and initiate inflammatory reactions in the mucosa will have unquestionable impact on improved therapy for peptic ulcer disease. PMID- 7881030 TI - Modeling the control of reticular thalamic oscillations by neuromodulators. AB - Compartmental models of thalamic reticular (RE) neurons were investigated based on current-clamp and voltage-clamp data. Spontaneous oscillations in the model arise from the interaction between inhibitory synaptic currents and the rebound burst of RE cells. These oscillations critically depend on the level of the resting membrane potential. A network of RE neurons can be switched between silent and sustained oscillatory behavior by modulating a leak potassium current through neuromodulatory synapses. These results suggest that neuromodulators, such as noradrenaline, serotonin and glutamate, can exert a decisive control over the oscillatory activity of systems of RE cells. The model may explain why the isolated RE nucleus oscillates spontaneously in vivo but not in vitro. PMID- 7881031 TI - Lipid peroxidation and platelet membrane fluidity--implications for Alzheimer's disease? AB - In humans, the fluidity of cell membranes generally decreases with age. Unexpectedly, several laboratories have found increased fluidity of platelet membranes (mainly endoplasmic reticulum) in patients with Alzheimer's disease (AD) compared with controls. In the present study, free radical induced lipid peroxidation was found to increase the fluidity of platelet membranes. Hydroxyl radicals were generated in the presence of Fe2+ and EDTA at low concentrations of ascorbate. It is hypothesised that platelet membranes are unable to restore their microviscosity by incorporating cholesterol. There may be a link between the result obtained in this study, the recently discovered decreased cholesterol content of affected AD neuronal membranes, and the increased frequency of epsilon 4 apolipoprotein E (a cholesterol carrier) found in AD patients. PMID- 7881032 TI - GABA and glycine frequently colocalize in terminals on cat spinal motoneurons. AB - In this ultrastructural study the colocalization of gamma-amino butyric acid (GABA) and glycine in terminals within cat lumbar motoneuronal cell groups was investigated and the frequency of this colocalization was determined. For this purpose the post-embedding immunogold technique was applied on serial sections, using antibodies directed against either GABA or glycine. Analysis of all labelled terminals in a random area of cat motoneuronal cell groups showed that 25 +/- 5% were labelled for GABA only, 29 +/- 6% were labelled for glycine only and 46 +/- 9% were labelled for both GABA and glycine, meaning that nearly two out of every three GABA-labelled terminals were also labelled for glycine and vice versa. Based on these results and on other data suggesting a high frequency of colocalization, it is concluded that in cat motoneuronal cell groups colocalization of GABA and glycine is the rule rather than the exception. PMID- 7881033 TI - Electrical signs of cortical involvement in the automatic control of grip force. AB - Evoked potentials were recorded in 10 subjects to assess cortical involvement in automatic control of grip force during restraint of a manipulandum held between finger and thumb. Brisk pulling loads elicited an increase in first dorsal interosseous EMG after 60.6 +/- 2.4 ms. Preceding this response were several time locked scalp potentials, the most significant being a widespread negativity that appeared first over the frontal cortex and peaked 19.5 +/- 1.8 ms before the EMG peak, and a positivity that followed the EMG by 24.3 +/- 5.4 ms. The slope of the negativity and the amplitude of the positivity were greater than during passive conditions, suggesting that these potentials reflect cortical processes associated with automatic regulation. PMID- 7881034 TI - Adaptive modification of oculomotor pursuit influences manual tracking responses. AB - We have addressed the question of whether adaptively modifying the oculomotor response to a visual pursuit stimulus has an influence on a related manual tracking response. Subjects used their unseen right hand to track targets moving at constant velocities while visually fixating a stationary LED. Manual tracking performance was compared before and after a 20 min period during which smooth pursuit eye movements alone were adaptively enhanced by adding 50% of the instantaneous eye position signal to target position. Compared with the preadaptation trials, hand gain was markedly increased during the postadaptation period. These results imply that the adaptation occurred at a level common to both motor systems, probably in CNS structures concerned with visual motion processing. PMID- 7881035 TI - Expression of GFAP in the striatum and its projection areas in response to striatal quinolinic acid lesion in rats. AB - Injection of quinolinic acid (QA) into the rat striatum is known to produce neuropathological and neurochemical features of Huntington's disease (HD). In the present study the astrocytic response two weeks following intrastriatal injection of either QA (240 nmol) or solvent (1 microliter) was examined using immunohistochemistry for GFAP. Striatal QA lesion resulted in a marked GFAP expression within the whole striatum which is due to neuronal degeneration. Furthermore, the reticular part of substantia nigra, globus pallidus and ventromedial thalamic nucleus revealed increases in GFAP expression without neuronal damage. As this remote astrocytic response is located only in striatal projection areas it seems to reflect transsynaptic changes in response to the lesion. PMID- 7881036 TI - Intrastriatal 3-nitropropionic acid: a behavioral assessment. AB - Systemic injections of 3-nitropropionic acid (3-NP) in Sprague-Dawley rats have led to (1) hypoactivity that resembles juvenile onset and advanced Huntington's disease (HD), and (2) impairment in contextual retention of passive avoidance. Since it has been established that 3-NP exerts its primary effects in the striatum, we selected intrastriatal injections to more thoroughly understand the direct behavioral effects of 3-NP. Each 14-week old rat received bilateral intrastriatal injections of one of the following: 500 and 750 nmol of 3-NP or vehicle (0.9% saline). At seven days following surgery, the animals were tested for spontaneous locomotor behavior and passive avoidance behavior. Results revealed deficits in both locomotor activity and passive avoidance learning. The animals injected with 500 and 750 nmol of 3-NP were significantly hypoactive compared with control animals. Similarly, the 2 groups of animals were severely impaired in the retention of passive avoidance compared with control. The 3 groups, however, did not differ in their acquisition of this learning task. Macroscopic analyses of brains of these animals revealed that 500 and 750 nmol of 3-NP caused severe loss of neuronal cell bodies and marked glial infiltration in the medial aspect of the striatum. Larger lesions showed a necrotic cavity at the injection site. In comparison with systemic administration of 3-NP, intrastriatal injections resulted in more profound hypoactivity, greater loss of passive avoidance retention, and more severe striatal damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881037 TI - Decreased pentylenetetrazol-induced expression of zif/268 in NGF-transgenic mice. AB - Expression of the proto-oncogene zif/268 was investigated by in situ hybridization in the hippocampus and cerebral cortex of nerve growth factor (NGF) transgenic mice during pentylenetetrazol (PTZ)-induced seizures. NGF-transgenic mice displayed normal basal levels of zif/268 mRNA in cortex and hippocampal formation except for the dentate gyrus which contained significantly reduced levels. PTZ induced a similar transient increase of zif/268 mRNA in cortex and Ammon's horn of normal and NGF-transgenic mice. On the other hand, increase of zif/268 mRNA in the dentate gyrus was significantly lower in transgenic mice. Reduced PTZ-induced activation of zif268 may reflect a decreased sensitivity of NGF-transgenic animals to epilepsy by direct or indirect interaction of NGF with immediate early genes. PMID- 7881038 TI - Differential cellular localization of three splice variants of the mGluR1 metabotropic glutamate receptor in rat cerebellum. AB - Antibodies were raised against C-terminal peptides of the splice variants a, b and c of the rat mGluR1 metabotropic glutamate receptor. Affinity purified antibodies each specifically reacting with mGluR1a, mGluR1b and mGluR1c were used to study the cellular localization of these receptors in rat cerebellum. The mGluR1a antibody strongly labelled Purkinje cells at their cells bodies, portions of their dendritic trees and numerous small punctate elements reminiscent of dendritic spines. Also labelled were some stellate, basket, Golgi and Lugaro cells. Granule cells were devoid of staining. The mGluR1b antibody strongly labelled Purkinje cell bodies and their dendrites at levels which varied within the same lobule of the vermis or the hemispheres. No significant labelling was observed at stellate, basket, Golgi and granule cells, while occasionally a fraction of basket cells and cerebellar glomeruli was moderately immunoreactive. The mGluR1c antibody strongly labelled cell bodies and thick principal dendrites of Purkinje cells but not dendritic spines. Immunonegative Purkinje cells were intermingled with strongly labelled ones in lobules 4-10, while in lobules 1, 2 and 3, no stained Purkinje cells were detected. The mGluR1c antibody also labelled stellate, basket, some Golgi and some Lugaro cells as well as granule cells. PMID- 7881039 TI - Fast desensitization of glutamate activated AMPA/kainate receptors in rat thalamic neurones. AB - An essential part of the excitatory afferent input to the thalamus is mediated by glutamate receptors of the AMPA/kainate type. In contrast to other regions of the mammalian CNS, the biophysical properties of these receptors have not been investigated in thalamic neurones. Using a fast transmitter application system we studied L-glutamate activated currents of cultured neurones in the whole cell and outside-out patch configuration. Current-voltage relationships and dose-response curves of whole cell recordings were in close correspondence to results obtained from other brain areas. Analysis of outside-out patch currents revealed two types of desensitization time constants of 3.0 and 10.2 ms, with the former close to the time constant of decay of miniature glutamatergic synaptic currents. PMID- 7881040 TI - The supraoculomotor cap: a region revealed by NADPH diaphorase histochemistry. AB - The distribution of the enzyme NADPH diaphorase in the region of the periaqueductal gray (PAG) was studied in the rat, rabbit, cat, monkey and human. In each species, the enzyme labelled a small band of neurones located below the level of the aqueduct and directly above the supraoculomotor gray in the middle of the antero-posterior extent of the PAG. The chemical specificity of this region suggests that it is distinct from the lateral PAG above and the supraoculomotor nucleus (Su3) below. We have named it the supraoculomotor cap (Su3C). PMID- 7881041 TI - Contribution of RGD sequence to neuronal migration in developing cerebral cortex. AB - The RGD sequence (Arg-Gly-Asp) is known to bind integrins and the synthetic RGD tripeptide inhibits cell adhesion and migration of cultured neuronal cells. However, it is not known whether migration of neuronal precursors in vivo during the cortical histogenesis of the mammalian telencephalon depends on the RGD sequence. To examine this possibility, the RGD peptide was injected into the telencephalic vesicle of mouse embryos. A hypoplastic cortical plate was induced and histological analysis and BrdU-immunohistochemistry revealed that the RGD sequence is involved in neuronal migration and proliferation in the telencephalon during formation of the cortical plate. PMID- 7881042 TI - Modulation of soman-induced neuropathology with an anticonvulsant regimen. AB - Rat hippocampus and piriform cortex were examined for pathological changes 48 hours after exposure to a convulsant dose of soman. Animals were treated with a low dose of atropine just after soman and were then injected, after 10 or 40 minutes of seizures, with both the anticonvulsant drugs NBQX and TCP. Atropine given alone counteracted the extensive neuronal loss due to soman in both areas without prevention of neuronal suffering. Comparatively, the complete anticonvulsant regimen, given before 40 minutes of seizures, totally prevented hippocampal soman-induced neuropathology. Neurones of piriform cortex were still suffering whatever the time of injection of the drugs. This emphasizes the need for a rapid and definitive anticonvulsant treatment just after soman intoxication to block the subsequent neurotoxic effect of nerve-agent exposure. PMID- 7881043 TI - Compartmental distribution of parvalbumin and calbindin D-28k in rat globus pallidus. AB - The cellular localization of parvalbumin (PV) and calbindin D-28k (CB) in the globus pallidus (GP) of rats was studied with double-immunohistochemical methods applied to single sections. The two calcium-binding proteins were found to be differentially distributed in GP. PV-positive cells were largely concentrated in the lateral part of GP where CB immunostaining was minimal. Their number and location varied along the rostrocaudal axis of GP. Pallidal PV cells were either large and multipolar or small and fusiform. In contrast, the medial part of GP was markedly enriched with CB neuropil but largely devoid of PV-positive cells. This spatial segregation indicates the existence of at least two different functional domains in the rat GP. PMID- 7881044 TI - Stimulus-specific fast oscillations at zero phase between visual areas V1 and V2 of awake monkey. AB - Synchronization of fast cortical oscillations (35-90 Hz) has been proposed as a basis of sensory integration. This hypothesis requires stimulus specific oscillations that occur synchronously in different cortical areas of awake animals. Here, we demonstrate the presence of, and phase-locking between, high amplitude stimulus specific oscillations (50-90 Hz) in striate (V1) and extra striate (V2) visual cortex of an awake monkey. Oscillations of multiple unit spikes and local field potentials occurred with an average V1-V2 phase difference near zero. This finding was unexpected because V1 and V2 are thought to be serially arranged in the primate's visual processing stream. However, near zero phase synchronization among cortical areas might enable fast and effective communication via the many reciprocal cortico-cortical connections for processes such as sensory integration. PMID- 7881045 TI - Angiotensin II AT1 receptor mediated contraction of the perfused rat cerebral artery. AB - The effect of angiotensin II on rat cerebral arteries was studied using isolated, perfused segments of anterior cerebral arteries. The infusion rate was set to maintain baseline intraluminal pressure at 75 mmHg. Angiotensin II (100 nM) increased the intraluminal pressure by 22.5 +/- 2.2 mmHg. Losartan, an AT1 antagonist, at 1 microM, completely blocked the effect of angiotensin II, whereas the AT2 ligands PD 123319 (1 microM) and CGP 42112 (1 microM) were ineffective. None of these AT1 or AT2 selective ligands alone displayed any agonist effects. The results show that angiotensin II induces contraction of the rat anterior cerebral artery by acting on AT1 receptors. PMID- 7881046 TI - Nerve growth factor levels in developing rat skin: upregulation following skin wounding. AB - Levels of nerve growth factor (NGF) in rat hindpaw skin, measured with a sensitive two-site enzyme-linked immunosorbent assay, show two peaks during normal development. The first (57 +/- 5 pg mg-1) occurs at embryonic days (E) 18 20 and coincides with the arrival of axon terminals into the hindpaw skin. The second, larger peak (132 +/- 10 pg mg-1), occurs later, around postnatal day (P) 21 and may be involved in maintenance of neuronal phenotype. Levels outside the two peaks stay relatively constant throughout development (30 pg mg-1). Skin wounding at birth produces a marked increase in NGF levels (149 +/- 25 pg mg-1) which declines after 4 days. This large increase is not observed if wounding is performed at older ages and may underlie the sensory hyperinnervation that accompanies neonatal wounds. PMID- 7881047 TI - Loss of neurones after long-term adrenalectomy in the adult rat hippocampal formation. AB - The effects of long-term adrenalectomy (ADX) on hippocampal neurones were investigated 5 months after surgery in male Sprague-Dawley rats. Cells in Nissl stained sections from ADX rats were counted and compared with those in sections from sham-operated rats. The ADX rats had a significantly reduced number of dentate granule cells. A novel finding was a significant reduction in the number of pyramidal cells in CA1, CA2, CA3 and CA4 regions of the hippocampus. Thus long term adrenalectomy causes loss of dentate granule cells and pyramidal neurones of the hippocampus. PMID- 7881048 TI - Segregation of computations underlying perception of motion discontinuity and coherence. AB - Motion is one of the most important cues for detecting discontinuities in images. The major dichotomy among theories of motion-defined discontinuity concerns whether the computations related to the extraction of discontinuity and large scale integration of motion signals are organized hierarchically or occur simultaneously in the brain. In this study we investigated the hierarchical nature of these computations using data from two patients with unilateral brain lesions on two psychophysical tasks: one requiring motion for spatial integration of direction in a stochastic motion field, and the other requiring motion to extract discontinuities in the same type of stimuli. The results showed a surprising double dissociation of deficits on these motion tasks which suggests that models for discontinuity detection requiring a single neural substrate for computing coherence and discontinuity are unlikely to be applicable to the human visual system. We discuss the computational implications of these results. Using morphometric three-dimensional reconstructions of the lesions from the magnetic resonance imaging data we suggest possible anatomical sites mediating these computations. PMID- 7881049 TI - Left putaminal activation when speaking a second language: evidence from PET. AB - The neural representation of the languages of the polyglot speaker has been highly controversial. We used positron emission tomography (PET) to investigate whether production in a second language (L2) involves the same neural substrates as that of a first language (L1) in normal bilingual subjects who learned L2 after the age of 5 years. Comparison of cerebral blood flow (CBF) when repeating words in L2 and repeating words in L1 yielded only a single significant CBF change: an increase in the left putamen. We hypothesize that this region plays a specific role for articulation in L2. The role of the putamen in articulation is supported by foreign accent syndrome (FAS), which can occur after left putaminal damage. The increased articulatory demands imposed by speaking a second language may require complex motor control for speech production in L2. PMID- 7881051 TI - The neuroprotective kappa-opioid CI-977 alters glutamate-induced calcium signaling in vitro. AB - The effect of the neuroprotective kappa opioid agonist CI-977 on glutamate (GLU) stimulated calcium signaling was studied in individual primary rat cortical neurons. Using laser scanning confocal microscopy and the fluorescent calcium probe fluo-3, both the sustained and biphasic intracellular calcium concentration [Ca2+]i changes induced by GLU (20-40 microM) were altered by CI-977 (25-100 nM), thereby shifting the neuronal population response from unbuffered to buffered patterns of [Ca2+]i flux. This effect was consistent with the previously demonstrated neuroprotective action of CI-977 against glutamate toxicity in vitro. The effect of CI-977 in altering GLU-induced [Ca2+]i signaling was attenuated by naloxone, consistent with a neuroprotective action of CI-977 at opioid receptors, presumably of the kappa subtype. PMID- 7881050 TI - Modulation of striatal aspartate and dynorphin B release by cholecystokinin (CCK 8) studied in vivo with microdialysis. AB - Sulphated cholecystokinin-8 (CCK-8) given into the neostriatum of the rat by in vivo microdialysis produced a concentration-dependent (1-100 microM) increase in extracellular aspartate (Asp) and dynorphin B (Dyn B), but not in glutamate, GABA or dopamine levels. The increase in Asp levels produced by 10 microM CCK-8 was approximately 10 fold and was inhibited (approximately 50%) by the CCKB antagonist L-365,260 (20 mg kg-1, i.p.), while the increase in Dyn B (approximately 2 fold) was totally abolished. Both increases were inhibited (approximately 50%) by local infusion of 10 microM of tetrodotoxin (TTX). Thus, CCK exerts modulatory effects in the basal ganglia, possibly by interacting with local neostriatal neurones releasing Asp, and with Dyn B-containing neurones projecting to the pars reticulata of the substantia nigra. PMID- 7881052 TI - Hg2+ increases the open probability of carbachol-activated Cl- channels in Aplysia neurons. AB - Carbachol and acetylcholine (ACh)-activated whole-cell chloride currents were recorded in identified neurons of Aplysia californica. Application of 0.1-10 microM HgCl2 potentiated the chloride response and reduced the rate of desensitization. To investigate the underlying mechanism we recorded single chloride channels in a cell-attached patch configuration. Recordings were performed successively on the same neuron with 1 microM carbachol and with 1 microM carbachol + 1 microM HgCl2, respectively. The slope conductance did not change significantly, but there was a manyfold increase in the open probability, Po. This may underlie the Hg(2+)-induced enhancement of carbachol- and ACh-evoked chloride currents in Aplysia neurons and may serve as a model for the neurotoxic effect of Hg2+ on the mammalian ACh receptor. PMID- 7881053 TI - K(+)- and transmitter-induced rises in [Ca2+]i in auditory neurones of developing rats. AB - Ca2+ ions are thought to play important roles in processes underlying neuronal plasticity such as synapse stabilization. We employed the Fura-2 technique on brainstem slices of neonatal rats to measure changes in intracellular Ca2+ ([Ca2+]i) in neurons of the lateral superior olive (LSO) in order to analyse whether these cells have functional Ca2+ channels when synaptic maturation takes place. Rises in intracellular Ca2+ could be induced by KCl-evoked depolarizations or by glutamate, but not by glycine or GABA. These results show that Ca2+ channels are present in developing LSO neurones and that many of them, if not all, belong to the voltage-sensitive type. We speculate that these channels play a role during ontogeny by mediating Ca(2+)-dependent mechanisms of synapse stabilization. PMID- 7881054 TI - Kainic acid inhibits protein amino acid incorporation in select rat brain regions. AB - Regional incorporation of labelled methionine into proteins was studied with quantitative autoradiography in different regions of the rat brain 2.5 h following systemic kainic acid administration. Labelled protein concentration was found reduced to approximately 40% of control values in the pyramidal cell layer of hippocampus, piriform, entorhinal and perirhinal cortices, ventral lateral septum and mediodorsal thalamic nucleus. These regions showed increased levels of label not incorporated into proteins, indicating that free labelled methionine was available for protein synthesis. Reduction of protein amino acid incorporation in those brain regions selectively affected by kainic acid may be involved in subsequent tissue damage. PMID- 7881055 TI - Investigations of the possible role for carbon monoxide (CO) in thermal and mechanical hyperalgesia in the rat. AB - Although recent reports have shown that production of nitric oxide (NO) is primarily involved in thermal hyperalgesia, the available behavioral evidence suggests that the signal transduction mechanisms involved in mechanical hyperalgesia, in general, do not involve NO. We report here that production of another labile gaseous messenger, carbon monoxide (CO) appears to be involved in mechanical but not thermal hyperalgesia produced in models of acute (intrathecal administration of glutamate receptor agonists) and persistent (intraplantar injection of zymosan) hyperalgesia. Together with results of previous studies, these results are consistent with a primary role for NMDA receptors and NO in thermal hyperalgesia and an involvement of AMPA and metabotropic glutamate receptors and CO in mechanical hyperalgesia. PMID- 7881056 TI - NBQX reduces threshold of protein synthesis inhibition in focal ischaemia in rats. AB - The effect of the AMPA antagonist NBQX on peri-infarct inhibition of cerebral protein synthesis (CPS) was studied in rats subjected to 3 h occlusion of the left middle cerebral artery (MCA). Cerebral blood flow and CPS were measured with double tracer autoradiography and local ATP content was monitored by bioluminescence imaging. In untreated MCA-occluded animals the perfusion threshold of ATP depletion in cerebral cortex was 17 +/- 5 ml 100 g-1 min-1 and that of CPS inhibition was 49 +/- 13 ml 100 g-1 min-1. NBQX treatment (2 x 30 mg kg-1 after vascular occlusion) reduced the perfusion threshold of CPS inhibition to 16 +/- 6 ml 100 g-1 min-1 (p < 0.05) whereas that of ATP depletion was not affected (11 +/- 6 ml 100 g-1 min-1). The NBQX-induced pharmacological improvement of peri-infarct CPS is similar to the previously described amelioration of peri-infarct CPS by MK-801 and may contribute to the reduction of infarct size by this treatment. PMID- 7881057 TI - Cocaine stimulant effects vary with cocaine levels in medial prefrontal cortex. AB - Rats treated with 10 mg kg-1 cocaine exhibited hyperlocomotion. Individual variation in the magnitude of this response was not correlated with serum cocaine concentration. Brain cocaine concentration, particularly in the medial prefrontal cortex, was highly correlated with the cocaine-induced locomotor stimulant effect. These findings indicate that variation in the uptake of cocaine into the brain is a critical variable in determining individual variation in its stimulant effects. PMID- 7881058 TI - A study of the synergism between metabotropic glutamate receptor activation and arachidonic acid in the rat hippocampus. AB - We report that activation of the metabotropic glutamate receptor by the specific agonist, trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD), increases release of glutamate only in the presence of a low concentration of arachidonic acid (AA). To identify the molecular mechanism underlying this effect, cAMP accumulation, inositol phospholipid metabolism and protein kinase C (PKC) activation were examined in synaptosomes prepared from hippocampus. ACPD increased cAMP accumulation, but this increase was not further enhanced in the presence of AA. ACPD and AA stimulated both inositol phospholipid turnover and PKC activity; a synergistic action was indicated by the additional stimulation in the presence of both agents. The increase in PKC activity, either directly, or indirectly by increased inositol phospholipid turnover, might therefore underlie the enhanced glutamate release. PMID- 7881059 TI - Silver impregnation reveals neuronal damage in cingulate cortex following 4 VO ischaemia in the rat. AB - An intriguing feature of global ischaemic cell loss is the sensitivity of certain neuronal populations and the relative resistance of others. Silver impregnation was used to ascertain the pattern and extent of cell loss following 15 min 4 VO ischaemia in the rat. Cell loss was observed primarily in the CA1 region of the hippocampus, as assessed by both cresyl violet and silver stains. However, degenerating neurones were most readily identifiable when impregnated with silver, and additional regions of neuronal loss were selectively revealed by silver staining in the hippocampal hilar region, dorsolateral striatum, neocortex and cingulate cortex. Damage to cingulate is a hitherto unreported consequence of 4 VO global ischaemia. This novel finding may have implications for ischaemic brain-behaviour relationships. PMID- 7881060 TI - Visual form discrimination from luminance or disparity cues: functional anatomy by PET. AB - With the purpose of elucidating the functional fields involved in the discrimination of visual form based either on luminance or binocular disparity cues, we used PET to measure changes in regional cerebral blood flow (rCBF) in ten volunteers while they performed visual discrimination tasks. The averaged standardized subtraction images (delta rCBF) were analysed for statistically significant changes between the form tasks and their reference tasks. Twenty cortical fields in the visual association areas and the prefrontal cortex were engaged by the discrimination of visual form based upon disparity cues, whereas only four fields showed increased activity during the discrimination of visual form created by luminance cues. The only functional field activated in both conditions was in the left fusiform gyrus. The present findings extend our earlier observations, namely that disparate functional networks of activated fields in the human brain can perform the discrimination of visual form perceptually defined by different visual cues. PMID- 7881061 TI - Long-term potentiation within the cat motor cortex. AB - Synaptic plasticity in the motor cortex of anesthetized cats was examined using intracellular recording and labeling techniques. Intracortical microstimulation (ICMS) was delivered in the superficial layers and recordings were made from cells in layer V. When the neuron responded to ICMS with an excitatory postsynaptic potential (EPSP), tetanic ICMS (100-200 Hz, 10-20 s) was delivered to the same site. Five of 19 cells which were examined and labeled with biocytin showed long-term potentiation (LTP) of the EPSP, and 12 cells showed post-tetanic potentiation (PTP) following the tetanic stimulation. All the examined cells were pyramidal neurons. These results demonstrate that plasticity exists within the intracortical connection of the motor cortex that may be involved in motor learning. PMID- 7881062 TI - Inhibition of phosphatase 2B prevents expression of hippocampal long-term potentiation. AB - The induction of long-term potentiation (LTP) in the CA1 region of the hippocampus is mediated by N-methyl-D-aspartate (NMDA) receptor-coupled calcium influx. In addition, calcium/calmodulin (CaM) has been demonstrated to play an essential role in the induction process. In the present study, a possible role of CaM-dependent phosphatase (phosphatase 2B, PP-2B, calcineurin) in the LTP process was examined by intracellular recordings in apical dendrites of CA1 pyramidal cells of adult guinea-pigs. In dendrites in which cypermethrin, a potent and specific inhibitor of PP-2B (IC50 40 pM), was intracellularly applied, tetanization generated only short-term increases (15-30 min) of excitatory responses. In the intracellular presence of allethrin, a weak inhibitor of PP-2B, LTP expression was not affected. These findings demonstrate that activation of PP 2B is a necessary condition for the expression of LTP in CA1 pyramidal cell dendrites. PMID- 7881063 TI - Sequential operation of disconnected cerebral hemispheres in split-brain patients. AB - When two concurrent sensorimotor tasks require separate responses, selection of the first response generally delays selection of the second. Dual-task performance was examined in four patients who had undergone surgical transection of the forebrain commissures including the corpus callosum. One light flash was presented to each visual field in succession, and patients made a choice response to each stimulus with the ipsilateral hand, thereby confining the tasks to separate hemispheres. All four showed dual-task interference very similar to that found with normal individuals. Therefore, still-intact subcortical structures must play a critical role in sequencing response selection processes (the 'dual task bottleneck'), confirming the distinction between the attentional limitations involved in planning actions and those involved in perceptual analysis. PMID- 7881064 TI - Interhemispheric transfer time and corpus callosum size. AB - We examined the relationship between the size of five mid-sagittal corpus callosum subareas (measured with in vivo magnetic resonance morphometry) and hand reaction times at dichotic consonant-vowel monitoring in fifty healthy young adults. Based on the reaction times, interhemispheric transfer times between auditory and motor brain areas were calculated and related to anterior and posterior corpus callosum subarea measurements. We found no relationship between the size of callosal subareas and auditory or motor interhemispheric transfer times. We did, however, find a significant correlation between mean reaction time and total corpus callosum size. Our results suggest that normal variation in callosal size or shape is not related to individual differences in auditory lateralization. Instead, callosal size may be associated with speed of information processing. PMID- 7881065 TI - Peripherally grafted human foetal dorsal root ganglion cells extend axons into the spinal cord of adult host rats by circumventing dorsal root entry zone astrocytes. AB - Human foetal dorsal root ganglia were grafted in place of native lumbar dorsal root ganglia in adult rat hosts. Between 4 weeks and 4 months later, the dorsal root entry zone (DREZ) in the grafted roots showed extensive peripheral outgrowth of astrocytic processes, in contrast to the normal 'smooth' interface between the peripheral and central nervous system compartments of the DREZ. Fibres originating from the grafted neurones and approaching the DREZ changed their direction of growth and entered the spinal cord through the pia by following blood vessels, grew into the grey matter and ramified there. These findings suggest that the DREZ astrocytes in vivo are non-permissive not only to mature peripheral regenerating axons, but also to growing axons from immature neurones. PMID- 7881066 TI - Lazaroids improve the survival of cultured rat embryonic mesencephalic neurones. AB - We have studied the effects of two lazaroids, U-74389G and U-83836E, on the survival of cultured rat dopamine neurones. Lazaroids are inhibitors of free radical formation and lipid peroxidation. Dissociated embryonic mesencephalic neurones were cultivated for 2 or 7 days under serum-free conditions with or without the addition of 0.3 microM of one of the lazaroids. Both lazaroids enhanced the survival of tyrosine hydroxylase immunoreactive, dopaminergic neurones both after 2 and 7 days in vitro to around 111-120% and 175-180% of controls, respectively. Since the total number of neurones was also increased following lazaroid treatment, it is unlikely that lazaroids exert their effects on only dopamine neurones. These findings suggest that oxidative stress plays an important role in the death of cultured embryonic dopamine neurones and that lazaroids may be potent neuroprotective agents in situations where dopaminergic neurones degenerate. PMID- 7881067 TI - Tooth pulp stimulation induces c-fos expression in the lateral habenular nucleus of the cat. AB - Detection of Fos protein expression by the peroxidase-antiperoxidase method was used to determine the area in the habenular (Hb) complex responding to electrical stimulation of the tooth pulp in the cat anaesthetized with pentobarbital. In the anaesthetic-injected group, the Fos-positive neurones were found bilaterally in the lateral Hb nucleus (HbL). Tooth pulp stimulation (intensity: 3 times the threshold for jaw-opening reflex) increased the number of positive neurones within the HbL by up to 300%, but did not induce any expression in the medical Hb nucleus. The increase in HbL was inhibited by morphine (2 mg kg-1, i.p.). These findings and the results of previous research suggest that HbL neurones are involved in defensive mechanisms by means of antinociception following noxious stimulation. PMID- 7881068 TI - Thioredoxin and metabolic regulation. AB - The regulatory function of thioredoxin, discovered in studies on carbon dioxide assimilation in photosynthesis, was extended to enzymes of related biosynthetic reactions of chloroplasts early on. More recently, thioredoxin was found to perform a range of regulatory functions--from the germination of seeds to the division and development of animal cells. The renaissance in knowledge relating to its activity suggests that thioredoxin will, on the one hand, emerge as a principal regulator of fundamental processes in the major forms of life and, on the other, find application in technology and medicine. PMID- 7881069 TI - The anatomy of phytochrome, a unique photoreceptor in plants. AB - Red and far-red light control of plant growth and development is mediated by the photoreceptor phytochrome. The way plants utilize red and far-red light is unique in nature, as are the molecular properties of phytochrome, the molecule that provides the mechanistic basis for this type of light perception. Much of what we know about how plants perceive red light has come from research on the structure and function of this photoreceptor. This review discusses the main structural features of phytochrome and some new ideas concerning the relationship between phytochrome structure and function. We propose that phytochrome functions as a dimer and that receptor recognition of phytochrome depends on its gross conformation. We also describe a conserved amino acid repeat within the phytochrome molecule and propose that this repeat is important for dimerization and/or phototransformation. PMID- 7881070 TI - Complementary chromatic adaptation: photoperception to gene regulation. AB - Many photosynthetic organisms can acclimate to the quantity and quality of light present in their environment. In certain cyanobacteria the wavelengths of light in the environment control the synthesis of specific polypeptides of the light harvesting antenna complex or phycobilisome. This phenomenon, called complementary chromatic adaptation, is most dramatically observed in a comparison of cyanobacteria after growth in green light and red light. In red light-grown cells the phycobilisome is largely composed of phycocyanin and its associated linker polypeptides (the latter are important for the assembly of the phycocyanin subunits and their placement within the light harvesting structure); the organisms appear blue-green in color. In green light-grown cells the phycobilisome is largely composed of phycoerythrin and its associated linker polypeptides; the organisms appear red in color. The ways in which these cyanobacteria sense their changing light environment and the regulatory elements involved in controlling the process of complementary chromatic adaptation are discussed in this review. PMID- 7881071 TI - Phytochrome transgenics: functional, ecological and biotechnological applications. AB - The phytochromes have important functions in regulating plant growth and development in response to signals perceived from the natural light environment. In particular, the phytochrome-mediated shade avoidance syndrome has major significance for competition between plants growing in natural dense communities. In recent years, the availability of DNA sequences coding for members of the phytochrome family has enabled the construction of transgenic plants that express these sequences to high levels. Introduced PHY genes expressed in heterologous or homologous hosts yield apoproteins that combine with chromophores and are physiologically functional. Physiological analysis of transgenic plants expressing introduced PHYA and PHYB coding sequences has contributed to understanding the functions of phytochromes A and B. Ecological experiments with transgenic PHYA expressers have provided a novel test of the adaptive plasticity hypothesis, and point the way to a transgenic programme to improve crop plants. PMID- 7881072 TI - Mutational analyses of light-controlled seedling development in Arabidopsis. AB - Arabidopsis mutants with decreased responses to light and mutants showing light responses in the dark have both been characterized. Some of the former mutants lack specific photoreceptors, such as the red/far-red light receptor phytochrome A, phytochrome B, or a putative blue light receptor, HY4. These have allowed the assessment of physiological functions of these photoreceptors. The mutants with light responses in the dark include some, such as det1 and cop1, that appear to identify light signal transduction components, and others, such as fus6, that may be less directly related to normal control of light responses. Double mutant studies suggest how the different gene products might interact. PMID- 7881073 TI - Phytochrome regulated gene expression. AB - Light is used by plants as a signal for many physiological and developmental processes. Phytochrome is the most extensively studied family of photoreceptors that plants use to perceive the presence and quality of light in their environment. While the initial action of the phytochrome molecule is not yet known, one important kind of response, changes in the expression of specific nuclear genes, has been intensively investigated. Although phytochrome-regulated promoters are complex and can also respond to other signals, specific DNA elements that are involved in conferring phytochrome responsiveness have been identified. Potential signal transduction pathway components include G proteins, cyclic GMP and Ca2+/calmodulin. In addition, the study of transcription factors involved in phytochrome-regulated gene expression has yielded insights into some of the final steps of transcriptional regulation by phytochrome. PMID- 7881074 TI - Blue light sensory systems in plants. AB - Plant development is influenced by many environmental stimuli, including light, temperature and gravity. Of these stimuli, light is of particular importance because plants depend on it for energy and, thus, for survival. Moreover, virtually all stages of plant development are regulated in part by light through the action of various photosensory systems. Examples of light-regulated processes include germination, stem growth, leaf and root development, tropic responses and flower induction. This review provides an analysis of recent investigations of blue light sensory systems in plants. Current results suggest that plants respond to blue light through a complex photosensory network that incorporates the action of multiple blue light perception systems. PMID- 7881075 TI - Illuminating the clock: circadian photobiology. AB - Light and circadian (daily) clocks are intimately related. Undoubtedly, the daily light/dark cycle has played a key role in the evolution of these oscillators. Now, light and dark signals synchronize these internal timekeepers to the precisely 24 h environmental cycle. Light also affects the period and amplitude of circadian rhythms. The expression of some 'light-responsive' genes are regulated by an intertwining of clock and light control mechanisms. These genes may help us to understand the evolution of circadian rhythmicity and can be employed as tools to identify and clone other genes which encode components of clock mechanisms or of their entrainment pathways. PMID- 7881076 TI - [Spiral computerized tomography, multiplane transesophageal echocardiography and magnetic resonance imaging in the diagnosis of thoracic aortic dissection]. AB - The aim of this study was the evaluation of spiral computed tomography (Spiral CT), multiplane transesophageal echocardiography (multiplane TEE) and magnetic resonance imaging (MRI) in the diagnosis of thoracic aortic dissection. 41 patients were examined: 30 with clinically suspected acute aortic dissection (14 Stanford A, 7 Stanford B), 11 with aortic repair (7/11 with persisting distal dissection). In 14 patients there was involvement of the supraaortic vessels. Sensitivity of Spiral-CT, multiplane TEE and MRI in the detection of aortic dissection was 100%, specificity was 100, 92, and 91%. In the assessment of involvement of aortic arch vessels sensitivity was 100, 67, and 60%, specificity was 100, 95, and 90%. The new imaging modalities Spiral-CT and multiplane TEE are equal to MRI in the detection of aortic dissection. In the assessment of the supraaortic branches Spiral-CT is superior to multiplane TEE and MRI and might become the method of choice. PMID- 7881077 TI - [Peripheral occlusive arterial diseases: comparison of diagnostic value of MRA and DSA]. AB - MATERIAL AND METHODS: In 59 patients with arterial flow disturbances 2-D inflow sequence of the abdominal and lower leg arteries were prospectively obtained on a 1.5 T MR-imager and were compared with additional DSA examinations. Supplementary Phase Contraste RSE ("Rapid Sequential Excitation") sequences were carried out in 29 patients. MRA and DSA angiograms were evaluated in random order by 4 readers using a questionnaire. The assessment of image quality were evaluated by variance analysis. Diagnostic performance of MRA and DSA was assessed by comparison of the readers' diagnostic assessments with reference diagnoses established by a radiologist and a vascular surgeon with full knowledge of all data concerning a patient. Image quality of inflow MRA was considered inferior to i.a. DSA (p < 0.001) and comparable with i.v. DSA (p = 0.1361). Image quality of RSE-MRA was inadequate (p < 0.001). Correspondingly, i.a. DSA was the superior and RSE-MRA the inferior imaging technique. The accuracy of inflow MRA in determining stenosis grade was 66% and that of RSE-MRA 59%. PMID- 7881078 TI - [Popliteal aneurysms: clinical aspects and diagnosis]. AB - PURPOSE: To identify clinical and radiological features allowing an early diagnosis of popliteal aneurysms. MATERIAL AND METHODS: History, clinical features and radiological findings of 23 patients with 37 aneurysms were reviewed. RESULTS: 14 patients presented with a history of a sudden onset of rest pain localised in the calf or foot. Arteriography found popliteal artery occlusion in 12 of them. Amputation was necessary in one patient in spite of immediate diagnosis and therapy. In two cases embolisation of the tibial vessels caused intermittent claudication. In at least 7 patients the underlying disease was not suspected until arteriography was performed. In 16/23 patients the presence of thrombus prevented direct visualisation of the aneurysm and there were only secondary angiographic signs of the underlying condition. Thus, arteriography may fail to diagnose popliteal aneurysms. In 21/22 cases colour Doppler sonography was quick and accurate in the assessment of patent and thrombosed aneurysms. CONCLUSION: In any patient with ischaemic symptoms of the lower extremity a thorough palpation of the popliteal fossa should be performed. In patients with a prominent popliteal pulse, in pulseless popliteal tumours and in patients arteriographically shown to have popliteal artery occlusion, a sonographic study of both popliteal fossae should be performed. PMID- 7881079 TI - [DIL vena cava filter. Initial experiences in 15 patients]. AB - DIL filters were permanently inserted through the cubital vein, using a 7-F catheter, in 15 patients and were followed up for six months in 12 patients. One filter could not be opened and 4 others were only partly open. Clinically there were no recurrences of pulmonary emboli. There were no complications from the correctly placed filters. Amongst the 4 incompletely expanded filters, two caused perforation of the cava, in one the cava thrombosed and in another the filter migrated to the bifurcation of the pulmonary artery. It follows that unexpanded filters should not be placed in the cava. Measurements in 10 patients showed the cava reduced to less than 10 mm lumen. In two cases the reduction of lumen was only slight, measuring more than 15 mm. The effect of the reduction in the lumen remains to be compared with that achieved by other filters. PMID- 7881080 TI - [Use of high-resolution algorithms and thick sections in computerized tomography staging of bronchial carcinoma]. AB - The purpose was to determine whether 8 mm slice sections with high resolution algorithms would prove superior to standard methods for the CT staging of bronchial carcinomas. The raw data from CT examinations in 50 patients using standard methods and the high resolution method was calculated, documented and compared. Within the lung parenchyma, small foci or metastases, peritumorous infiltrates, bronchial narrowing, bronchial outlines, vessels and areas of poor aeration were significantly clearer. Pleural thickening and subpleural fat stripes were also better seen. Abnormalities in the mediastinum were equally well shown. High resolution algorithms with 8 mm slice sections are recommended for routine staging of bronchial carcinomas, particularly if the calculations can be done quickly, as is possible on modern apparatus, without increasing the duration of the examination. PMID- 7881081 TI - [Inversion recovery RARE: clinical use of a T2-weighted CSF-suppressed rapid sequence]. AB - Inversion-Recovery RARE is a strongly T2-weighted fast sequence in which the CSF appears dark. This sequence was used in more than 100 patients. Retrospective analysis of 80 patients with cerebrovascular and inflammatory disease was carried out. The IR-RARE sequence proved to be particularly suitable for identifying small lesions in the neighbourhood of the subarachnoid space. We illustrate the typical contrast provided by this sequence, and describe its characteristics, exemplifying the advantages it offers for the diagnosis of multiple sclerosis, cerebral microangiopathy and brain infarction. PMID- 7881082 TI - [Quantification of signal modulation of hematopoietic bone marrow in gradient echo sequences. Results of phantom and proband studies with simultaneous determination of T2* relaxation times]. AB - The signals from spongy bone on gradient echo sequences depend on the fat and water proton content as well as the differences in magnetic susceptibility at the border between the trabeculae and the bone marrow. From the signal intensities for different echo times, signal modulation was quantified by a special algorithm and at the same time the T2 relaxation time was calculated. Using a fat-water phantom, it was shown that the product of the initial fat and water signal intensity (modulation coefficient) is applicable to indicate the extent of signal modulation and thereby the chemical shift and, moreover, to indicate changes in the fat/water ratio sensitively. In 16 individuals of different ages (23 to 64 years, average 42.4 years) there was a tendency for the T2 relaxation time from the spongiosa of lumbar vertebrae to increase with age, this can be explained by a reduction in the trabecular content, causing reduction in the magnetic inhomogeneity of the bone marrow. The results indicate the usefulness of the sequence and the mathematical model for evaluating the spongy bone in cases of osteoporosis and of malignant haematological disorders. PMID- 7881083 TI - [Radiation exposure of radiologists during angiography: dose measurements outside the lead apron]. AB - The aim of this study was to provide practical information to angiographers concerning radiation exposure to body parts not covered by lead aprons. Individual doses to the neck and hands of radiologists measured in micro-Sieverts were obtained during the course of 80 angiographies of various types. The number of diagnostic and interventional procedures, which might lead to exceeding permissible doses, have been calculated. Possibilities of estimating doses during angiography by means of parameters such as screening times were examined statistically. Especially with regard to the hands, estimations of the doses are insufficient (correlation r = 0.21). Radiologists who undertake much angiographic and particularly interventional work may reach exposure levels requiring protective measures in addition to lead aprons. PMID- 7881084 TI - [Comparison of input grey values and contrast profiles: a contribution to the discussion on optimization of evaluation parameters in storage phosphorus radiography]. AB - On comparing the individual imaging stages in conventional and digital image radiography it becomes evident that a significant advantage of the digital method is the possibility to adapt the image character and exposure dose individually to various problems requiring an answer. To take advantage of this it is imperative to optimise image processing with care, especially contrast processing. No systematic procedure based on objective criteria had existed to date. This paper describes a method of taking into account both the diagnostic significance of the structures to be imaged and their distribution within the relevant density range, in order to arrive at the best possible contrast conversion. A prerequisite is to know for every kind of imaging which distribution of grey values pertaining to the relevant structures can be expected before digital image processing (initial grey values). This distribution determines the most favourable contrast conversion. The processing parameters for several types of imaging were optimised by this method. The method is demonstrated via thoracic images of newborn and children. PMID- 7881085 TI - [ROC analysis in post-processing of image data in digital thoracic radiography]. AB - PURPOSE: To examine the extent to which digital luminescence radiography (DLR) can be used for the imaging of pulmonary nodules and interstitial lung disease in chest radiography without any loss of image quality. Additionally: to examine whether post-processing of image data can optimise the recognizability of varied image details. MATERIALS AND METHODS: Detail perceptibility studies were performed on an anthropomorphic thorax phantom with simulated nodules and small linear and reticular details. Under standard conditions, digital luminescence radiographs were obtained in 7 different image modes, and these were compared with a 200-speed screen-film system. The detection of these systems was evaluated in an ROC analysis on the basis of 19,200 individual observations. RESULTS: Edge enhancement or application of high-frequency-enhancing small filter kernels (S 5) slightly improves the detection of linear structures; however, the illustration of nodular details is markedly reduced. Larger filter kernels (S 20, S 40) make a definitive detection possible--not only of circular, but also of linear details. CONCLUSIONS: Storage phosphor radiographs are equal to the tested analog screen film-system. The optimization of post-processing can be helpful in the prevention of routine multiple documentations. PMID- 7881087 TI - [Hyperostosis of the cranial vault in osteogenesis imperfecta. A further observation with CT findings]. PMID- 7881086 TI - [Animal experiment studies on the influence of fatty infiltration of liver cells on tissue relaxation times and signal changes in magnetic resonance tomography]. AB - Using a spectrometer (n = 60) in vitro and MRT imaging (n = 8) in vivo, we studied the influence of fatty changes of liver cells on the relaxation times of the liver (two animal models of fatty liver disease/orotic acid, L-ethionine). Induction of fatty degeneration of the liver by means of an orotic acid diet resulted in pure deposition of fat in the liver without any histological or serological proof of inflammatory changes. Although accumulation of triglyceride in the liver reduced the T1 relaxation time only relatively slightly (-15%), there was good correlation (r = 0.88) between fat content and T1. There was also good correlation (r = 0.92) between T2 and histological fat content. Inflammatory changes besides fatty deposition were seen both serologically and histologically in the L-ethionine model, so that the fatty content did not correlate with T1. In vivo MRT imaging showed that spin-echo sequences are inappropriate for diagnosing fatty infiltration of the liver despite the relaxation time changes produced by the fatty deposition. On the other hand, chemical-shift imaging sequences are very sensitive to identify fatty deposits, and are also independent of any additionally existing inflammatory changes. PMID- 7881088 TI - [Chylothorax after esophageal resection]. PMID- 7881089 TI - [Occlusion of the subclavian artery in thoracic outlet syndrome. 3-dimensional imaging with spiral computerized tomography (SCT)]. PMID- 7881090 TI - [Lung abscesses in fire eaters: radiological findings]. PMID- 7881091 TI - High-grade immunoblastic sarcoma: an unusual type of a primary cardiac non Hodgkin lymphoma. PMID- 7881092 TI - [Health risks due to radiation exposure]. AB - Recent data analyses of several ongoing epidemiological studies, in particular the Life Span Study of Hiroshima and Nagasaki, have led to new estimates of risks due to radiation-induced cancer. The risk coefficients published by the International Commission on Radiological Protection (ICRP) in 1991 are 0.5% Sv-1 for leukaemia and 4.5% Sv-1 for solid cancers. For adults the mean latency periods for radiation-induced leukaemia are about 15 years, for solid cancers more than 40 years. Using the organ specific risk coefficients several examples are given for risk estimates for some frequently applied radiological procedures. The results are compared with various generally known risks of everyday life. Some specific problems involved in risk communication are considered. PMID- 7881093 TI - [Functionally determined area changes in the oro-pharyngo-laryngeal vocal tract of singers as shown by magnetic resonance tomography]. AB - The oro-pharyngeal-laryngeal resonating spaces were studied in 12 singers at varying stages of their training by means of medio-sagittal MRI images, and the results were compared. The singers were requested to sing /a/ /u/ and /i/ at various pitches and with increasing loudness. The total oro-pharyngo-laryngeal areas were integrated by means of the MRI sections. The relationship between the oro-pharyngeal and pharyngo-laryngeal areas was determined, as well as their ratio to total area. With increasing volume there was increase in the area of the oro-pharyngeal component with no change in the pharyngo-laryngeal component. The relationship of the partial areas depends on the extent of training of the singer. PMID- 7881094 TI - The SPORE Program of the Vincent T. Lombardi Cancer Research Center. PMID- 7881096 TI - Matrix-degrading proteases in hormone-dependent breast cancer. AB - Proteases have emerged as important modulators of the metastatic capacity of cancer. However, metastasis is regulated by multiple other characteristics of the tumor cell and evidence suggests the participation of multiple classes of proteases. In the present article we review the literature concerning the potential biological roles of multiple proteases in breast cancer. In particular, we focus on the gelatin-degrading metallo proteinase and on a novel 80 KDa matrix degrading protease that appears to be commonly expressed in hormone dependent breast cancer cell lines. PMID- 7881095 TI - Transfected MCF-7 cells as a model for breast-cancer progression. AB - The MCF-7 human breast carcinoma cell line has been used as a recipient for eukaryotic plasmid expression vectors to determine the effects of growth factor and growth factor receptor overexpression on the estrogen-dependent, antiestrogen sensitive and poorly metastatic phenotypes exhibited by this line. Overexpression of some members of the erbB family of ligands and receptors were found to have some effects on these phenotypes. However, only when two members of the fibroblast growth factor family, FGF-1 and FGF-4, were overexpressed was progressive in vivo growth observed is either ovariectomized nude mice without estrogen supplementation or in mice that received tamoxifen treatment. FGF transfected cells also exhibited an increased ability to form micrometastases. The implications of these results with regard to the possible role of the paracrine and autocrine effects of angiogenic growth factor production in breast cancer progression are discussed. PMID- 7881097 TI - Modulation of breast cancer progression and differentiation by the gp30/heregulin [correction of neregulin]. AB - In the last decade we have come to understand that the growth of cancer cells in general and of breast cancer in particular depends, in many cases, upon growth factors that will bind to and activate their receptors. One of these growth factor receptors is the erbB-2 protein which plays an important role in the prognosis of breast cancer and is overexpressed in nearly 30% of human breast cancer patients. While evidence accumulates to support the relationship between erbB-2 overexpression and poor overall survival in breast cancer, understanding of the biological consequence(s) of erbB-2 overexpression remains elusive. Our recent discovery of the gp30 has allowed us to identify a number of related but distinct biological endpoints which appear responsive to signal transduction through the erbB-2 receptor. These endpoints of growth, invasiveness, and differententiation te have clear implications for the emergence, maintenance and/or control of malignancy, and represent established endpoints in the assessment of malignant progression in breast cancer. We have shown that gp30 induces a biphasic growth effect on cells with erbB-2 over-expression. We have recently determined the protein sequence of gp30 and cloned its full length cDNA sequence. We have also cloned two additional forms to the ligand, that are believed to be different isoforms. We are currently expressing the different forms in order to determine their biological effects. To elucidate the cellular mechanisms underlying cell growth inhibition by gp30, we tested the effect of this ligand on cell growth and differentiation of the human breast cancer cells which overexpress erbB-2 and cells which express low levels of this protooncogene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881098 TI - Regulation of estrogen receptor expression. PMID- 7881099 TI - Vitamin D receptors in breast cancer cells. AB - 1,25-(OH)2-Vitamin D3, the active metabolite of vitamin D, is a secosteroid hormone with known differentiating activity in leukemic cells. Studies have demonstrated the presence of vitamin D receptors (VDR) in a wide range of tissues and cell types. Antiproliferative activity of 1,25-(OH)2-vitamin D3 has been documented in osteosarcoma, melanoma, colon carcinoma, and breast carcinoma cells. This study was designed to analyze vitamin D receptor level in breast cancer cells as a marker of differentiation and as a predictor of growth inhibition by 1,25-(OH)2-vitamin D3. VDR messenger RNA was found to be present in relatively high levels in well-differentiated cells and in low levels in poorly differentiated cells. All cell lines had detectable VDR mRNA. Radiolabeled ligand binding assay showed a similar pattern. MCF-7 and T47D cells, which express VDR at moderate levels, showed significant growth inhibition by 10(-9) M1,25-(OH)2 vitamin D3 (p < 0.05). MDA-MB-231 cells, which have very low levels of VDR, demonstrated no growth inhibition by 1,25-(OH)2-vitamin D3 at concentrations up to 10(-6) M. Based on these results it can be stated that VDR expression is lost with de-differentiation and that receptor is essential for the antiproliferative response to 1,25-(OH)2-vitamin D3. PMID- 7881100 TI - Membrane proteases as potential diagnostic and therapeutic targets for breast malignancy. AB - Metastasizing cancer cells can invade the extracellular matrix using plasma membrane protrusions, termed invadopodia, that contact and dissolve the matrix. Various membrane associated proteases localized on the invadopodial membranes are responsible for the extracellular matrix degradation. Work from our laboratory shows that secreted proteases including Gelatinase A, and high molecular weight integral membrane proteases are associated with cell surface invadopodia. Three cell types, including chicken embryonic cells transformed by Rous sarcoma virus, human malignant melanoma cell line LOX, and human breast carcinoma cell line MDA MB-231, retain the invasive phenotype in vitro, express invadopodia, degrade and enter into a fibronectin-rich collagenous matrix. We suggest that invadopodium associated proteases are ideal targets for the diagnosis and treatment of cancer as their presence in association with primary tumors may signal increased metastatic potential. An approach toward the development of new prognostic markers for breast malignancy involved production of monoclonal antibodies directed against membrane proteases in a mixture of glycoproteins. Double immunofluorescent technique using a known invadopodium marker is designed to select specific monoclonal antibodies colocalizing at the invasion front, on invadopodia of cancer cells. Membrane protease accessibility at the cell surface can therefore be exploited for therapeutic advances by the development of specific antibodies and inhibitors that block their activities, and by the use of monoclonal antibodies to target cytotoxic molecules to micrometastases. Also, this same accessibility may potentially be used to detect surface proteases on micrometastases or to detect components shed by micrometastases in serum. PMID- 7881101 TI - Mechanisms of EGF receptor regulation in breast cancer cells. AB - Overexpression of the EGF receptor in breast cancer correlates with poor prognosis and failure on endocrine therapy for both ER-/EGFR+ and ER+/EGFR+ tumors, suggesting a role for EGFR in the progression to hormone independence. The identification of specific DNAse I hypersensitive site patterns for the EGFR gene in ER+ vs. ER- cells implicates regions of the EGFR first intron in up regulation of EGFR, while estrogen regulation studies indicate the involvement of a repressor(s) in the maintenance of low levels of EGFR. Based on these findings, a multi-step model is proposed for the progression of breast cancer from a hormone-dependent, ER+/EGFR-phenotype to an aggressive, hormone-independent, ER /EGFR+ stage. PMID- 7881102 TI - Hormonal carcinogenesis in breast cancer: cellular and molecular studies of malignant progression. AB - We have established and characterized a series of variant cell lines in which to identify the critical factors associated with E2-induced malignant progression, and the acquisition to tamoxifen resistance in human breast cancer. Sublines of the hormone-dependent MCF-7 cell line (MCF7/MIII and MCF7/LCC1) form stable, invasive, estrogen independent tumors in the mammary fat pads of ovariectomized athymic nude mice. These cells retain expression of both estrogen (ER) and progesterone receptors (PGR), but retain sensitivity to each of the major structural classes of antiestrogens. The tamoxifen-resistant MCF7/LCC2 cells retain sensitivity to the inhibitory effects of the steroidal antiestrogen ICI 182780. By comparing the parental hormone-dependent and variant hormone independent cells, we have demonstrated an altered expression of some estrogen regulated genes (PGR, pS2, cathepsin D) in the hormone-independent variants. Other genes remain normally estrogen regulated (ER, laminin receptor, EGF receptor). These data strongly implicate the altered regulation of a specific subset or network of estrogen regulated genes in the malignant progression of human breast cancer. Some of the primary response genes in this network may exhibit dose-response and induction kinetics similar to pS2, which is constitutively upregulated in the MCF7/MIII, MCF7/LCC1 and MCF7/LCC2 cells. PMID- 7881103 TI - Insulin-like growth factor mediated stromal-epithelial interactions in human breast cancer. AB - The prominent 'desmoplastic' or stromal reaction seen in many invasive breast carcinomas lead to early speculation that stromal cells play a role in breast cancer pathogenesis. Experimental evidence now supports this hypothesis and interactions between stromal cells and epithelial cells appear to be important for both normal mammary development and neoplasia. The identification of genes that are selectively expressed in the stroma of malignant breast lesions has recently provided new insights into the molecular basis of stromal-epithelial interactions. Stromally expressed genes include growth factors, proteases and extracellular matrix proteins, all biological activities with potential roles in malignant progression. Investigations discussed here concern the nature of the paracrine signals provided by malignant epithelial cells that activate changes in stromal gene expression, the effect that the stromally derived factors have on the behavior of malignant epithelial cells and the identification of novel factors and receptors in either stroma or epithelia that contribute to their mutual interactions. These questions will be addressed in the context of this laboratory's studies on insulin-like growth factors, as these molecules show marked differences in stromal expression between benign and malignant breast tissue and thus provide a useful paradigm for investigations into the paracrine environment of an evolving breast tumor. PMID- 7881104 TI - Transcriptional regulation of multidrug resistance in breast cancer. AB - The development of cross-resistance to many natural product anticancer drugs, termed multidrug resistance (MDR), is one of the major reasons why cancer chemotherapy ultimately fails. This type of MDR is often associated with over expression of the MDR1 gene product, P-glycoprotein (Pgp), a multifunctional drug transporter. The expression of MDR in breast tumors is related to their origination from a tissue that constitutively expresses Pgp as well as to the development of resistance during successive courses of chemotherapy. Therefore, understanding the mechanisms that regulate the transcriptional activation of MDR1 may afford a means of reducing or eliminating MDR. We have found that MDR1 expression can be modulated by type I cAMP-dependent protein kinase (PKA), opening up the possibility of modulating MDR by selectively down-regulating the activity of PKA-dependent transcription factors which upregulate MDR1 expression. High levels of type I PKA occurs in primary breast carcinomas and patients exhibiting this phenotype show decreased survival. The selective type I cAMP dependent protein kinase (PKA) inhibitors, 8-Cl-cAMP and Rp8-Cl-cAMP[S] may be particularly useful for downregulating PKA-dependent MDR-associated transcription factors, and we have found these compounds to downregulate transient expression of a reporter gene under the control of several MDR1 promoter elements. Thus, investigations of this nature should not only lead to a greater understanding of the mechanisms governing the expression of MDR, but also provide a focus for pharmacologic intervention by a new class of inhibitors. PMID- 7881105 TI - Perinatal factors increase breast cancer risk. AB - Emerging evidence suggests that breast cancer may originate during early life. In particular, offspring of mothers who during pregnancy exhibited behaviors that are associated with increased incidence of breast cancer, may be at risk. These behaviors include intake of high fat diet or alcohol, or stressful life style. We have found that neonatal exposure to handling that leads to improved ability to cope with stress, reduces 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats. Further, our results indicate that maternal exposure to high fat diet increases the incidence of DMBA-induced mammary tumors in female offspring. High fat diet also increases serum 17 beta-estradiol (E2) levels in pregnant animals. These results support the hypothesis that in utero concentrations of estrogens play a critical role in the vulnerability to develop breast cancer. The mechanism of estrogen action might be related to its effect on the induction of epithelial hyperplasia and altered breast differentiation. These events then increase the rate of genetic/epigenetic changes that increase the possibility of neoplastic transformation. Increased pregnancy estrogens may also lead to behavioral alterations in the offspring. This could explain the proposed association between certain behavioral patterns and increased tumorigenity. Our results in transgenic mice overexpressing transforming growth factor alpha (TGF alpha) are in accordance with this interpretation. The male TGF alpha mice exhibit elevated serum E2 levels, impaired ability to cope with stress, increased voluntary alcohol intake and high incidence of spontaneous hepatocellular tumors. These findings indicate that animal models offer a unique opportunity to investigate the role of timing of risk behaviors on breast cancer. They are also useful in the attempts to understand the mechanism of early estrogen action on mammary tumorigenesis. PMID- 7881106 TI - Metabolism of breast cancer cells as revealed by non-invasive magnetic resonance spectroscopy studies. AB - The basis for the use of nuclear magnetic resonance (NMR) spectroscopy as a tool to study the metabolism of breast cancer cells is described. The differences between proton (1H), carbon (13C), and phosphorus (31P) NMR methods is explained, and the techniques of cell extracts, cell suspensions and perfusion methods for cells are detailed. In order to perfuse cells they are preferably trapped in a gel matrix, either in the form of a thread or a bead. The gel must have appropriate properties that enables efficient oxygenation and availability of nutrients and drugs. The metabolic effects of perfusion of breast cancer cells with nutrients, drugs, and hormones are reported, and the clinical relevance of these results and methods are outlined. PMID- 7881107 TI - Antiestrogen resistance in ER positive breast cancer cells. AB - Acquisition of the antiestrogen resistance by breast cancer cells in vivo may result from a variety of mechanisms. The main pathway appears to involve loss of estrogen receptor (ER) expression or selection for ER negative cells among heterogenous population of tumor cells. However, clinical data suggest that, in about 30% of the cases, antiestrogen resistance arises even in the presence of estrogen receptors. Postulated mechanisms leading to the latter phenotype include selection for variant receptor forms during treatment, development of novel metabolic pathways for the drug, loss of nuclear co-factors, or activation of signal transduction pathway that cross activate ER signals. We have used an in vitro experimental system utilizing LY-2 cell line, an ER positive and antiestrogen resistant MCF-7 cell variant, to study the mechanism of antiestrogen resistance in the presence of functional ER. Result from a complementation experiment suggests that LY-2 phenotype is a recessive trait. Cloning of the genetic defect in the LY-2 cells would provide further insight for the mechanism of antiestrogen resistance in ER positive breast cancer cells. PMID- 7881108 TI - Psycho-oncology and breast cancer: a paradigm for research and intervention. AB - The recent award to the Lombardi Cancer Research Center of a National Cancer Institute funded Specialized Program of Research Excellence (or SPORE) grant in Breast Cancer has created a unique opportunity to develop and apply a comprehensive psycho-oncology research model that can serve as a paradigm for studies in this area across disease sites. In the following article, the rationale for and design of the psycho-oncology research program at Georgetown is presented. Areas of research are outlined, specific topics of concern within these are delineated and progress towards addressing these is briefly reviewed. PMID- 7881109 TI - Differentiation state and invasiveness of human breast cancer cell lines. AB - Eighteen breast cancer cell lines were examined for expression of markers of epithelial and fibroblastic differentiation: E-cadherin, desmoplakins, ZO-1, vimentin, keratin and beta 1 and beta 4 integrins. The cell lines were distributed along a spectrum of differentiation from epithelial to fibroblastic phenotypes. The most well-differentiated, epithelioid cell lines contained proteins characteristic of desmosomal, adherens and tight junctions, were adherent to one another on plastic and in the basement membrane matrix Matrigel and were keratin-positive and vimentin-negative. These cell lines were all weakly invasive in an in vitro chemoinvasion assay. The most poorly-differentiated, fibroblastic cell lines were E-cadherin-, desmoplakin- and ZO-1-negative and formed branching structures in Matrigel. They were vimentin-positive, contained only low levels of keratins and were highly invasive in the in vitro chemoinvasion assay. Of all of the markers analyzed, vimentin expression correlated best with in vitro invasive ability and fibroblastic differentiation. In a cell line with unstable expression of vimentin, T47DCO, the cells that were invasive were of the fibroblastic type. The differentiation markers described here may be useful for analysis of clinical specimens and could potentially provide a more precise measure of differentiation grade yielding more power for predicting prognosis. PMID- 7881110 TI - Sphingosine-1-phosphate, a novel second messenger involved in cell growth regulation and signal transduction, affects growth and invasiveness of human breast cancer cells. AB - This review will focus on the role of sphingosine and its phosphorylated derivative sphingosine-1-phosphate (SPP) in cell growth regulation and signal transduction. We will show that many of the effects attributed to sphingosine in quiescent Swiss 3T3 fibroblasts are mediated via its conversion to SPP. We propose that SPP has appropriate properties to function as an intracellular second messenger based on the following: it elicits diverse cellular responses; it is rapidly produced from sphingosine by a specific kinase and rapidly degraded by a specific lyase; its concentration is low in quiescent cells but increases rapidly and transiently in response to the growth factors, fetal calf serum (FCS) and platelet derived growth factor (PDGF); it releases Ca2+ from internal sources in an InsP3-independent manner; and finally, it may link sphingolipid signaling pathways to cellular ras-mediated signaling pathways by elevating phosphatidic acid levels. The effects of this novel second messenger on growth, differentiation and invasion of human breast cancer cells will be discussed. PMID- 7881111 TI - Breast cancer gene therapy: transgenic immunotherapy. AB - A number of studies have demonstrated that potent anti-tumor immunity can be induced using cytokine gene transfer, a strategy termed transgenic immunotherapy. Our aim is to express cytokine genes in the vicinity of tumor cells, either by transducing tumor cells themselves, or by delivering cytokine-expressing endothelial cells to tumor sites. We compared the ability of cytokine-expressing tumor cells or endothelial cells to inhibit the tumorigenesis of MDA-MB-435 breast cancer cells in athymic nude mice. Retroviral vectors containing either human interleukin 2 (hIL-2) or interleukin 1 (hIL-1 alpha) were used to transduce MDA-MB-435 cells or human umbilical vein endothelial cells (HUVEC). Using a modified MTT bioassay and an ELISA specific for hIL-2, 43 of 70 MDA-MB-435 clones transduced with IL-2 were found to secrete between 100-800 units of IL-2/10(6) cells/24 hr. hIL-2 and hIL-1 alpha-transduced HUVEC secreted 40 ng/IL-2/10(6)/24 hr and 1.8 ng/10(6)/24 hr, respectively. To facilitate in vivo tracking of tumor cells, both nontransduced and IL-2-expressing MDA-MB-435 cells were genetically marked with the E. coli lacZ gene and selected using flow cytometry. To study in vivo tumorigenicity, cells were injected into the mammary fat pad of athymic nude mice: (1) lacZ/MDA-MB-435 cells injected alone formed tumors in all animals; (2) IL-2-expressing lacZ/MDA-MB-435 cells did not form any tumors; (3) co-inoculation of MDA-MB-435/IL-2, or HUVEC/IL-2, or HUVEC/IL-1 alpha with lacZ/MDA-MB-435 cells prevented or delayed tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881113 TI - Clinical breast cancer research core. AB - The primary purpose of the clinical breast cancer research core is to support the research of the five SPORE projects, and the high priority projects and other studies of SPORE Investigators. The specific aims of the CORE are as follows: The first aim is to provide the project investigators of the SPORE grant with access to a clinical research facility. A second aim is to provide the investigators with a clinical database linked to the tumor bank for the facilitation of studies to improve the diagnosis and prognosis of breast cancer. A third aim is to develop and maintain a serum and DNA lymphocyte bank which will enable investigators to take prognostic or therapy response factors developed in the laboratory and evaluate their clinical significance. PMID- 7881114 TI - Research integration. PMID- 7881115 TI - Quality measurement in nursing: where are we now? AB - The American Nurses' Association commissioned a review of the nursing quality measurement literature to understand the state of the art of nursing quality measurement and to influence policy makers to include nurse-sensitive quality measures in health care reform legislation. Using both computer and hand searching methods, 158 articles that described measuring nursing care quality were abstracted. Recommendations based on the analysis of literature include implementing the Nursing Minimum Data Set (NMDS), documenting nursing hours per patient and the education level of nurse providers in large data sets, implementing a system for determining appropriate outcomes for patients that is sensitive to each individual's potential for self-care or recovery, and continued research directed toward nurse-sensitive outcomes. PMID- 7881112 TI - Collagen induced MMP-2 activation in human breast cancer. AB - Matrix metalloproteinase-2 (MMP-2), a zymogen requiring proteolytic activation for catalytic activity, has been implicated broadly in the invasion and metastasis of many cancer model systems, including human breast cancer (HBC). MMP 2 has been immunolocalized to carcinomatous human breast, where the degree of activation of MMP-2 correlates well with tumor grade and patient prognosis. Using Matrigel assays, we have stratified HBC cell lines for invasiveness in vitro, and compared this to their potential for metastatic spread in nude mice. HBC cell lines expressing the mesenchymal marker protein vimentin were found to be highly invasive in vitro, and tended to form metastases in nude mice. We have further discovered that culture on collagen-I gels (Vitrogen; Vg) induces MMP-2-activator in highly invasive but not poorly invasive HBC cell lines. As seen for other MMP 2-activator inducing regimens, this induction requires protein synthesis and an intact MMP-2 hemopexin-like domain, appears to be mediated by a cell surface activity, and can be inhibited by metalloproteinase inhibitors. The induction is highly specific to collagen I, and is not seen with thin coatings of collagen I, collagen IV, laminin, or fibronectin, or with 3-dimensional gels of laminin, Matrigel, or gelatin. This review focuses on collagen I and MMP-2, their localization and source in HBC, and their relationship(s) to MMP-2 activation and HBC metastasis. The relevance of collagen I in activation of MMP-2 in vivo is discussed in terms of stromal cell: tumor cell interaction for collagen I deposition, MMP-2 production, and MMP-2-activation. Such cooperativity may exist in vivo for MMP-2 participation in HBC dissemination. A more complete understanding of the regulation of MMP-2-activator by type I collagen may provide new avenues for improved diagnosis and prognosis of human breast cancer. PMID- 7881116 TI - Ethnocultural sensitivity and measurement of consumer satisfaction. AB - Stemming from the diversity in the U.S. population, ethnocultural factors no longer can be ignored when defining and assessing consumer satisfaction. Likewise, there is a critical need for process models that consider consumer heterogeneity. Continuous quality improvement (CQI) programs must look beyond whether or not services are accessible and cost-effective. The processes must also measure if services are acceptable and appropriate for a target population. This article describes how the discipline of anthropology can provide useful tools to obtain critically needed ethnocultural information. PMID- 7881117 TI - Developing effective measurement tools: a case study of the Consumer Emergency Care Satisfaction Scale. AB - Development of valid and reliable instruments to assist nurse researchers and clinicians in meeting the needs of consumers is an avenue toward continuous quality improvement (CQI). This article explains validity and reliability and the process of constructing a valid and reliable scale. The development of the Consumer Emergency Care Satisfaction Scale, a measure of quality nursing care in the emergency department, is used as the example. PMID- 7881118 TI - The customer is always right: patients' perceptions of psychiatric nursing actions. AB - In this age of consumerism, consideration should be given to patients' perceptions of interactions with the health care provider as a factor in assessing the quality of care provided. This article describes a study of 100 psychiatric inpatients in a large urban medical center who evaluated 50 commonly used psychiatric nursing actions. Significant differences were found between the general psychiatric patient population and the substance abuse population in perception of helpfulness and frequency of performance with 7 of the 50 nursing actions. As the consumer's perception of the effectiveness of nursing actions is determined, emphasis can be given to those interventions when planning patient care. PMID- 7881119 TI - Measuring patient satisfaction: a case study. AB - Health care providers are under tremendous pressure to meet consumer demands in order to compete in the rapidly changing health care arena. Through evaluating patient satisfaction, health care providers can learn what the consumer wants from the health care system. This article informs the reader of issues surrounding patient satisfaction data collection instruments, especially the problem of lack of standardization. That is, each instrument measures satisfaction according to different standards. This article presents a case study analysis of one patient satisfaction data collection instrument entitled the Picker-Commonwealth Survey on Patient-Centered Care. Suggestions for revision and further work are addressed. PMID- 7881120 TI - The consumer's role in quality: partnering for quality outcomes. AB - Partnering with the patient in the planning and delivery of care to achieve high quality outcomes is a goal shared by health care providers. The achievement of a full partnership with the patient often varies based on the communication skills of individual nurses. To provide more consistency, Patient Standards of Care (SOCs) were created that are written from the patients' viewpoint in lay terms and are condition-specific. The content includes commitments of the health care team, patient care issues and concerns, what the team will do, what the patient can do, and outcome expectations. The end result is to promote the patients' engagement in their own care through the sharing of accountabilities for desired outcomes. PMID- 7881121 TI - Determining intensity of need of high-risk maternal and infant clients. AB - Sound funding decisions by policymakers require data that relate health care services to both client need and client outcome. However, client need for care is not easy to express quantitatively, particularly in the realm of preventive and health promotion services. Application of the Community Health Intensity Rating Scale (CHIRS) with high-risk infants and prenatal clients revealed that differences in intensity of need, particularly in contextual and behavioral domains, helped to explain variation in amount of care received. The CHIRS holds promise of providing the language and measurement with which to articulate client need as the basis for cost-effective multidisciplinary care. PMID- 7881122 TI - Using the Nursing Interventions Classification to implement Agency for Health Care Policy and Research guidelines. AB - The mandate for establishing guidelines for assessing effectiveness has been given to the Agency for Health Care Policy and Research (AHCPR). This agency has published 10 practice guidelines for practitioners to use. The present task for practitioners is to establish how effectively use these guidelines. Nurse researchers at the University of Iowa have provided a practical standardized language of nursing interventions that will help nurses demonstrate and communicate current nursing practice. This Nursing Interventions Classification (NIC) will allow nurses to implement the guidelines, demonstrate nursing input for patient care, and make nursing visible to consumers and other health care providers. PMID- 7881123 TI - The changing role of the consumer in health care quality. AB - Traditionally, health care quality has been provider defined and focused, even though consumers define and evaluate health care quality. And, there is no relationship between consumer and provider perceptions of quality. Importantly, consumers use their evaluations when they decide to sue, recommend or return for services, and comply with treatment regimens. This article examines the changing role of the consumer in health care quality, explicates the need for a change in the health care paradigm, and suggests strategies for increasing patient participation in health care planning and quality assessment. PMID- 7881124 TI - Given the shift to more collaborative quality approaches, is there still a role for nursing quality coordinators? PMID- 7881125 TI - Cellular invasion and collagen type IX in the primary corneal stroma in vitro. AB - During different stages in the development of the avian cornea, various collagen types have been shown to participate in matrix formation and have been implicated in morphogenesis. One of these is the fibril-associated collagen type IX. This molecule is present when the primary corneal stroma is in a compact state, but rapidly disappears just prior to stromal swelling and its invasion by mesenchymal cells. The temporospatial pattern of the disappearance of type IX collagen in the developing cornea suggests that this molecule may be involved in stabilizing the primary corneal stromal matrix by interacting either with other type IX collagen molecules or with other matrix components. To explore further whether the removal of type IX collagen is involved in stromal swelling, we have employed an in vitro culture system in which swelling of the primary stroma and mesenchymal cell invasion can be experimentally manipulated by culturing chick corneal explants on a Nuclepore filter support in the presence or absence of an associated lens. We have also examined the effect of exogenously added human recombinant tissue inhibitor of metalloproteinases (TIMP-1) on the presence of type IX collagen and cellular invasion. When stage 25-26+ corneal explants were cultured with an associated lens, the primary stroma did not swell; immunohistochemically detectable type IX collagen was still present, and mesenchymal cell invasion failed to occur. Conversely, when the same stages of corneal explants were cultured without an associated lens, the primary stroma swelled; type IX collagen disappeared, and mesenchymal cell migration occurred. Under both conditions, however, the type II collagen of the stroma, which is known to be a component of the striated fibrils, remained clearly detectable and with time even seemed to increase in amount. This result is consistent with the proposition that type IX collagen is one factor involved in maintaining the primary stroma as a compact matrix, possibly by functioning as a bridging/stabilizing factor. When TIMP was added to cultures of corneal explants, type IX collagen remained detectable in focal regions, suggesting that one or more metalloproteinases are involved in the removal of the type IX collagen. In addition, some of these type IX-containing regions contained mesenchymal cells, suggesting that in addition to type IX collagen other factors are likely to be involved in regulating mesenchymal cell migration. PMID- 7881126 TI - Expression of epidermal growth factor family gene members in early mouse development. AB - Transcription of four members of the epidermal growth factor (EGF) family, EGF, TGF-alpha, Amphiregulin, and Cripto, was investigated in the ovulated unfertilized egg and preimplantation embryo using cDNA libraries. EGF was present as a maternal message only, TGF-alpha was present at low levels in each library, Amphiregulin was not detected, and Cripto transcripts were first detected in the blastocyst cDNA library. In situ hybridization studies of the implanting embryo revealed Cripto expression localized to the entire ectoderm and then to the rapidly growing ectoplacental cone. At gastrulation, Cripto was detected in the primitive streak and developing mesoderm. During organogenesis, Cripto localized to the developing heart. Two Cripto transcripts were detected: one is confined to the early embryo and teratocarcinoma cells, and the other, first found in the fetus, is the major form detected in adult organs. PMID- 7881127 TI - Mapping the origin of the avian enteric nervous system with a retroviral marker. AB - The enteric nervous system is largely formed from the vagal neural crest which arises from the neuroaxis between somites 1-7. In order to evaluate the contribution of different regions of the vagal crest to the enteric nervous system, we marked crest cells by injecting somites 1-10 with a replication defective spleen necrosis virus vector which contains the marker gene lacZ. After incubation in X-gal, lacZ-positive blue cells were found in the wall of the gut in three locations. Most were found at the peripheral edge of the developing circular muscle and within the developing submucosa, sites characteristic of developing ganglia. LacZ-positive cells in these ganglionic sites were always surrounded by HNK-1 immunostained cells, confirming their neural crest origin. LacZ-positive cells were also seen in a third location, the circular muscle layer of the esophagus and crop, and were separated from the HNK-1 positive ganglionic elements. These cells in the circular muscle are probably muscle cells derived from labeled mesodermal cells of the somite. Injection of somites 3, 4, 5, and 6 resulted in the largest percentage of preparations with lacZ-positive crest derived cells and in the largest number of positive cells in the gut. After injection of these somites, lacZ-positive crest-derived cells were found in all regions of the gut from the proventriculus to the rectum. Very few positive crest derived cells were found in the esophagus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881128 TI - Expression of M-cadherin protein in myogenic cells during prenatal mouse development and differentiation of embryonic stem cells in culture. AB - Molecules regulating morphogenesis by cell-cell interactions are the cadherins, a class of calcium-dependent adhesion molecules. One of its members, M-cadherin, has been isolated from a myoblast cell line (Donalies et al. [1991] Proc. Natl. Acad. Sci. U.S.A. 88:8024-8028). In mouse development, expression of M-cadherin mRNA first appears at day 8.5 of gestation (E8.5) in somites and has been postulated to be down-regulated in developing muscle masses (Moore and Walsh [1993] Development 117:1409-1420). Affinity-purified polyclonal M-cadherin antibodies, detecting a protein of approximately 120 kDa, were used to study the cell expression pattern of M-cadherin protein. It was first visualized in somites at E10 1/3 and could be confined to desmin positive, myotomal cells. At all subsequent prenatal stages, M-cadherin was only found in myogenic cells of somitic origin. The detection of the protein at E10 1/3 suggests a translational delay of M-cadherin mRNA of 1 to 2 days (E8.5 vs. E10 1/3). This was further supported by the finding that during differentiation of ES cell line BLC6 into skeletal muscle cells in culture, expression of M-cadherin mRNA can be detected 2 days prior to M-cadherin protein. During prenatal development, the pattern of M cadherin expression changes: In E10 1/3 embryos and also in myotomal cells of later stages, M-cadherin is evenly distributed on the cell surface. In developing muscle masses (tested at E16 to E18), however, M-cadherin protein becomes clustered most likely at sites of cell-cell contact as indicated by double labelling experiments: M-cadherin-staining is the positive image of laminin negative areas excluding the presence of a basal lamina at M-cadherin positive sites. Furthermore, M-cadherin is coexpressed with the neuronal cell adhesion molecule N-CAM which has been shown to mediate cell-cell contact in myogenic cells. In summary, our results are in line with the idea that M-cadherin might play a central role in myogenic morphogenesis. PMID- 7881129 TI - Morphogenesis of the murine node and notochordal plate. AB - Development of the node and formation of the notochordal plate in gestational day 7-9 mice (Theiler stages 10-14) has been documented principally with scanning electron microscopy (SEM) and cell fate analyses utilizing DiI and/or CFSE as a cell label. With SEM, cells composing these two populations are initially identifiable at stage 10 at the ventral midline of the rostral half of the embryo. They can be recognized by their relatively small ventral surface area, as compared to that of the peripherally adjacent prospective gut endodermal cells, and by the presence on the ventral side of each cell of a prominent single, central cilium, which is lacking on endodermal cells. At stage 10, the node is located at the apex of the cup-shaped embryo. It represents the rostral end of the primitive streak (although its structure differs from that of the rest of the streak), and it consists of a localized two-layered area (i.e., epiblast and the most caudal aspect of the notochordal plate). By stage 11, the notochordal plate constitutes a relatively broad, circular area (at the level of the node) that tapers rostrally into a narrower midline strip (beneath the future floor plate of the neural tube). The tip of the notochordal plate terminates rostrally at the much broader prechordal plate, which underlies the future forebrain level of the neuraxis. The prechordal plate cells, like the ventral node and notochordal plate cells, each have a relatively small ventral surface area and displays a single central cilium on their ventral surface. The most caudal aspect of the notochordal plate remains morphologically distinct on the dorsal, midline surface of the open gut through stage 13; the more rostral levels progressively fold off from the roof of the gut to form the definitive notochord. Videomicroscopy reveals that the cilia extending from the ventral surfaces of the cells of node and of the prechordal and notochordal plates are motile. The potential significance of this motile behavior remains unknown. Labeling studies, which marked cells in both the dorsal and ventral layers of the node, reveal that the stage-10 node contributes cells to the notochordal plate and overlying midline ectodermal cells of the neural plate, the future floor plate of the neural tube.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7881130 TI - Prospective fate map of the mouse primitive streak at 7.5 days of gestation. AB - Fluorescent dyes were used in the present study to map three rostrocaudal levels of the primitive streak of mouse embryos at 7.5 days of gestation. Injections at the most rostral level, the 1/4 streak level, principally labeled cells of the paraxial mesoderm, including mesenchyme in the head, and somites and segmental plate mesoderm in the trunk. Injections at the intermediate level, the 1/2 streak level, principally labeled cells of the lateral plate mesoderm of the trunk. Injections at the most caudal level, the 3/4 streak level, principally labeled cells of the extraembryonic mesoderm at the periphery (i.e., caudolateral portion) of the embryo adjacent to the developing amnion, yolk sac, and allantois. However, injections placed at all three primitive-streak levels provided some labeled cells to the areas of the ingressed mesoderm derived from immediately adjacent levels, suggesting that prospective mesodermal areas are not fully spatially segregated from one another at this stage. These data combined with those from a companion study in which the structure of the node was defined and its derivatives were mapped (Sulik et al. [1994] Dev. Dyn. 201:260-278) allowed us to construct a prospective fate map of the mouse primitive streak at 7.5 days of gestation. This map revealed that mediolateral subdivisions of the ingressed mesoderm were arrayed in rostrocaudal sequence within the primitive streak, such that more rostral levels of the streak contained prospective medial cells (e.g., notochord and paraxial mesoderm), intermediate levels contained prospective intermediate cells (e.g., intermediate mesoderm or nephrotome and lateral plate mesoderm), and more caudal levels contained prospective lateromost cells (e.g., extraembryonic mesoderm). Prospective mesodermal cells, with the exception of those of the notochord, ingressed bilaterally from the primitive streak, contributing to the mesoderm on both the right and left sides of the axis. Our prospective fate map of the mouse primitive streak at 7.5 days of gestation, when compared to a map of the avian primitive streak at a comparable stage of development (Schoenwolf et al. [1992] Dev. Dyn. 193:235-248), demonstrates that considerable congruity exists between the locations of mesoderm precursor cells in birds and mammals. Thus, similar morphogenetic movements underlie mesoderm formation during avian and mammalian gastrulation. Moreover, prospective mesodermal locations within the mouse primitive streak correspond to recently described patterns of early gene expression (Sasaki and Hogan [1993] Development 118:47-59; Takada et al. [1994] Genes Dev. 8:174-189; Rossant, person communication). PMID- 7881131 TI - Temporally and spatially restricted expression of apolipoprotein J in the developing heart defines discrete stages of valve morphogenesis. AB - During cardiac valve morphogenesis, a series of interactions between the mesodermal-derived myocardium and the overlying endothelium lead to condensed leaflet structure formation. At the atrioventricular (AV) canal, endocardial cells are transformed by specialized underlying myocardial cells into endocardial cushions, and then remodeled into mitral and tricuspid valves. Aortic and pulmonary valves develop by a similar mechanism in the primitive outflow tract. Few genes exhibit restricted spatiotemporal expression in these critical embryonic structures, thus limiting the clues to the sequence of molecular events necessary for valvulogenesis. Apolipoprotein J (ApoJ), a secreted glycoprotein expressed in a variety of cell types at tissue interfaces, exhibits a highly restricted and dynamic expression pattern in the developing heart. ApoJ transcripts were detected in mice at day 9.0 of gestation in the wall of the developing truncus arteriosus. By day 10, intense signal occurred in a thin layer of myocardial cells adjacent to developing endocardial cushions of both atrioventricular canal and truncus arteriosus. No apoJ mRNA was present in the overlying endocardial cushions until day 13.5 when prevalvular condensation begins. Intense expression occurred in the stromal connective tissue throughout leaflet formation. The highly restricted spatiotemporal expression pattern of apoJ in the developing heart implicates its role in the morphogenesis of the AV canal and outflow tract into cardiac valves. PMID- 7881132 TI - Guanine nucleotide binding regulatory proteins: their characteristics and identification. AB - Many biological signals are processed by the binding of chemicals to cell surface receptors. Signals are switched to intracellular language via guanine nucleotide binding regulatory proteins (G-proteins) which are present in all eukaryotic cells. Thus, G-proteins serve as interfaces between receptor-response coupling. Two forms of G-proteins have been reported: conventional G-proteins which are heterotrimeric and consist of alpha, beta, and gamma subunits, and monomeric small molecular weight G-proteins which are generally found as single polypeptides. Recently, high molecular weight G-proteins have also been described. The family of G-proteins contains multiple genes that encode the alpha, beta, or gamma subunits. G-proteins play a pivotal role in excitation contraction coupling in smooth muscle function and control metabolic and secretory processes. In this review article, we have given a brief overview on the characteristics and methodology for the identification of G-proteins. The heterotrimeric G-proteins are generally identified by Western blotting and ADP ribosylation with bacterial toxins. The monomeric and high molecular weight G proteins have been identified by [35S]GTP delta S overlay technique and photoaffinity labeling, respectively. Recently, the use of molecular genetic probes has made it possible to investigate the expression of the message for various G-proteins. PMID- 7881133 TI - A method to perform direct transcutaneous intrathecal injection in rats. AB - This work describes a method for performing direct intrathecal (i.t.) injections in rats without introducing a spinal catheter. Its ease of use in awake animals yields rapid and reproducible results with no sign of motor impairment. The quality of each injection was ensured by the observation of an injection-induced tail-flick. A 10-microL injection of methylene blue was well localized yielding a very limited diffusion along the spinal cord. The method was validated by demonstrating that morphine (i.t.) had a marked antinociceptive effect and that naloxone (i.t.) blocked the effect of systemic (s.c.) morphine in mononeuropathic rat. PMID- 7881134 TI - Relationship between QaT and RR intervals in rats, guinea pigs, rabbits, and primates. AB - The ECG is routinely used in many species to monitor effects of drugs. While it is relatively easy to measure both PR and QRS, measurement of QT is complicated by the fact that this interval can change with heart rate. In order to compensate for variations in QT due to variations in heart rate, various correction factors have been used, including those of Bazett and Hodges. Such corrections were devised for humans and may have limited applicability in other species. We have systematically varied heart rate in anesthetized rats, guinea pigs, rabbits, and primates using procedures such as vagal stimulation, direct atrial stimulation, injection of cold saline and drugs, including anesthetics, and measured the resulting QT (as QaT and related measures). Over a wide range of heart rates we tested various formulas for their value in correcting for the variation in QT interval associated with changes in heart rate. In rats the "QT" interval did not change appreciably with heart rate. In the other species QaT intervals varied in the expected manner with heart rate in that they decreased with tachycardia and increased with bradycardia. Various formulas were tested for their utility in correcting measures of the QaT interval (QaTc) for changes in heart rate in guinea pigs, rabbits, and primates. In species other than rats, there was little difference between the various formulas in their ability to increase the precision of QaTc and the normality of its distribution, although the best correction is that derived from the regression (either linear, square root, or polynomial) equation relating RR and QaT. PMID- 7881135 TI - A serosa-searing apparatus for producing gastric ulcer in rats. AB - Chronic ulcer models produced by serosa-searing method are very similar histologically to the ulcer healing process occurring in humans. In an effort to produce a serosa-searing chronic ulcer model in rats, we devised a new balance type apparatus. This searing apparatus is capable of changing adequately both temperature and duration of time. Furthermore, the pressure which serves to bring the searing iron tip into contact with the stomach serosa surface can also be precisely changed. Optimal conditions for reproducing the serosa-searing ulcer model were at 65 degrees C and in 5 sec. Moreover, in order to evaluate the effects of pressure, various pressure levels (A: 5 g, 17.68 g/cm2; B: 10 g, 35.37 g/cm2; C: 15 g, 53.05 g/cm2; D: 20 g, 70.74 g/cm2; E: 25 g, 88.42 g/cm2; F: 30 g, 106.10 g/cm2; G: 35 g, 123.79 g/cm2 (+/- 1 g, 0.149 g/cm2)) of 5-sec duration at 65 +/- 0.1 degrees C were used. Macroscopically, gastric mucosal lesions were most clearly observed in a pressure-related manner 7 days after the procedure. Histologically, definite deep ulcerations (UI-III or UI-IV) were observed at pressure level C (15 g, 53.05 g/cm2) or more. The highest incidence (87%) of histological gastric ulcers (UI-IV) was observed in pressure level E (25 g, 88.42 g/cm2). The healing process was observed at 40 to 60 days postoperatively. At 100 days after the procedure, recurrences were observed both macroscopically and histologically. In conclusion, this new apparatus is very useful for reproducing a chronic ulcer model for observing the healing and recurrence process. PMID- 7881136 TI - An ultrasonographic method for the evaluation of dexmedetomidine on micturition in intact rats. AB - We describe a simple, noninvasive, nontraumatic, and reproducible ultrasonographic method to determine the effect of the alpha 2-adrenoceptor agonist dexmedetomidine in anesthetic dose (300 micrograms/kg subcutaneously) on the micturition reflex in intact rats. The bladder volumes were estimated by an ellipsoid equation. To validate the reliability of the method, an in vitro model assessment also was performed. The mean difference between estimated and instilled volumes were 27.3 microL (-21.61, 76.23). The highly significant correlation (r = 0.98, p < .001) indicates that the ultrasonography with the equation is a reliable tool. After the dexmedetomidine administration to intact rats, urine dribbling occurred at 30 +/- 4.8 min. The volume threshold for urination was 2100 +/- 100 microL. Although dribbling of the urine was observed almost continuously, significant differences were not observed between bladder volumes obtained at any time (from 10 to 100 min). This study indicates that the alpha 2-adrenoceptor agonist dexmedetomidine inhibits the micturition reflex in intact rats. The method described, which is both noninvasive and nonpainful, may therefore be widely used to quantify in small animals pharmacological effects on the urinary bladder. PMID- 7881137 TI - Interaction of MAO inhibitors and dietary tyramine: a new experimental model in the conscious rat. AB - The aim of this study was to assess a new model for tyramine-induced pressor effects in the rat. The predictivity of the test is improved by simulating the real clinical situations where tyramine is ingested with food and beverages containing the amine. The pressor effect was investigated after oral administration of tyramine in a feed preparation or in a water solution by continuously recording blood pressure just above the aorta junction via a left carotid catheter. The response was quantified by measurement of peak systolic blood pressure and as the percentage of tyramine-sensitive rats (TSR) in which the maximal pressor response to the amine was higher than 30 mm Hg (clinical risk threshold). Tyramine elicited, after oral administration (by gavage), a statistically significant dose-dependent increase in blood pressure from the dose of 10 mg/kg in solution (i.e. 23 +/- 3 mm Hg, N = 36) and 40 mg/kg in feed preparation (i.e., 20 +/- 2 mm Hg, N = 26). Almost all rats showed a systolic blood pressor increase higher than 30 mm Hg after oral administration of tyramine at a dose of 80 mg/kg p.o. in solution (TSR = 96%). Administration of tyramine in food (80 mg/kg) significantly delayed the time of the peak blood pressure (13 +/- 2 min instead of 7 +/- 0.5 min in solution, p < .001). Under these conditions, the tyramine threshold dose of TYR 30 (dose inducing an average response equivalent to the clinical risk threshold) was 14 mg/kg p.o. in solution and 67 mg/kg p.o. in feed preparation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881138 TI - Streptozotocin-induced diabetes mellitus in spontaneously hypertensive rats: a pathophysiological model for the combined effects of hypertension and diabetes. AB - The present study was undertaken to investigate the combined effects of hypertension and streptozotocin-induced diabetes mellitus in the rat. Accordingly, four groups of rats were studied: Wistar Kyoto rats (WKY), diabetic WKY, spontaneously hypertensive rats (SHR) and diabetic SHR, respectively. The mean arterial blood pressure was increased in hypertensive animals compared to normotensive animals. The base excess in the diabetic rats was higher than that of normoglycemic animals. An elevated glucose concentration was found in the blood and urine of streptozotocin-treated rats. Ketone bodies were detected in the urine and blood of the diabetic rats. Mortality rates after treatment were not different among the four groups. In separate experiments, isolated working hearts of the various groups were set up and analyzed. For the maximal left ventricular pressure (mm Hg) the following values were formed: 110.0 +/- 2.6, 93.6 +/- 2.7, 93.4 +/- 3.0, and 87.5 +/- 2.4, respectively. The wet heart weights, dry heart weights, and body weights of the diabetic rats were lower than those of normoglycemic animals. The wet heart weight/body weight ratio, however, was increased by diabetes and hypertension (0.43 +/- 0.01, 0.47 +/- 0.01, 0.47 +/ 0.01, and 0.54 +/- 0.02, respectively). There were no significant differences between the water content of the hearts from the four different groups. Pathologic examination of the hearts showed myocardial hypertrophy and medial hypertrophy of coronary arteries in diabetic and hypertensive animals. There was no difference in relative collagen content in the hearts of the four groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881139 TI - A reevaluation of antibiotic prophylaxis in laparoscopic cholecystectomy. AB - Antibiotic prophylaxis for cholecystectomy, although somewhat controversial, is nevertheless a routine component of surgical care. With the advent of laparoscopic cholecystectomy, this routine practice of antibiotic prophylaxis needs to be reevaluated. The present investigation was undertaken to determine the incidence of postsurgical infection in patients receiving antibiotic prophylaxis compared with patients receiving chlorhexidine gluconate scrub the evening before surgery. A total of 448 patients were enrolled in the study. Thirty-two of these patients were excluded because of the presence of intrinsic risk factors for infection. Two hundred twenty-eight patients received antibiotic prophylaxis, and 188 patients were enrolled in the non-antibiotic group. A total of 14 infections occurred in the antibiotic prophylaxis group, whereas no infections occurred in the chlorhexidine group. These results suggest that meticulous antiseptic skin cleansing is sufficient for prevention of postsurgical infection following laparoscopic cholecystectomy. Antibiotic prophylaxis should be used only in those patients exhibiting intrinsic risk factors, such as cholecystitis. PMID- 7881140 TI - General anesthesia by mask with spontaneous ventilation during brief laparoscopic inspection of the peritoneum in children. AB - We prospectively examined the cardiorespiratory changes seen with general anesthesia by mask with spontaneous ventilation during brief laparoscopic inspection of the peritoneum in children. Anesthesia consisted of isoflurane in 50% oxygen/air and a caudal epidural block. The patient was allowed to ventilate spontaneously without assistance. Baseline measurements of heart rate, systolic/diastolic blood pressure (BP), end-tidal CO2 (PETCO2), tidal volume, respiratory rate, and oxygen saturation were recorded every 1 min for 5 min before the start of laparoscopy and every minute during the laparoscopic procedure. A total of 20 patients were enrolled in the study, ranging in age from 15 to 80 months (mean 40.8 months) and in weight from 10.5 to 27 kg (mean 15.9 kg). The length of the laparoscopy varied from 3 to 18 min (mean 6.9 min). No significant changes (increase or decrease of 20% from baseline) of heart rate or BP occurred. Oxygen saturation remained at 98%-100% throughout the procedure in all patients. The baseline tidal volume before the start of laparoscopy was 6.27 +/- 1.9 mL/kg and increased to 7.3 +/- 2.2 mL/kg during laparoscopy (p = 0.01). The baseline respiratory rate was 27.7 +/- 7.0 breaths/min and increased to 33.5 +/- 7.2 breaths/min during laparoscopy (p = 0.0001). PETCO2 increased from a baseline value of 37.5 +/- 6.5 to 44.6 +/- 6.8 mm Hg (p = 0.0001). The increase in PETCO2 was 10 or greater in 3 patients and exceeded 50 mm Hg in 3 patients, with a maximum value of 66 torr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881141 TI - Laparoscopic pneumoperitoneum: impact of body habitus. AB - The purpose of this study was to determine the relationships among pneumoperitoneum pressure, CO2 insufflation volume, and patient height, weight, and body mass index. Forty-one male patients undergoing laparoscopic urologic procedures prospectively had a record made of the delivered volume of CO2 during insufflation to attain intraabdominal pressures of 5, 10, 15, 20, 25, and 30 mm Hg. The relationship of the delivered volume of CO2 insufflated and the intraabdominal pressure was compared statistically to the patient height, weight, and body mass index. In addition, six domestic female pigs underwent pneumoperitoneum, and the abdominal volume was calculated for intraabdominal pressures of 0, 5, 10, 15, 20, 25, and 30 mm Hg. Four different commercially available 10-mm trocars were tested for force required for placement at intraabdominal pressures of 15 and 30 mm Hg. There was a direct relationship between delivered volume of CO2 insufflated and the pneumoperitoneum pressure. There was no significant relationship between the delivered volume of CO2 insufflated at a given intraabdominal pressure and the patient height, weight, or body mass index. During insufflation, 94% of the abdominal volume is achieved by insufflating to 15 mm Hg. There is no significant difference in the force required for insertion of different ports at 15 mm vs 30 mm Hg pressure. Increasing the abdominal pressure to 30 mm Hg provides a 50% increase in the volume of CO2 insufflated vs a standard 15 mm Hg pneumoperitoneum. However, this additional volume does not significantly change the actual abdominal volume or diminish the pressure necessary to insert a trocar. PMID- 7881142 TI - The effect of drains in laparoscopic cholecystectomy. AB - A prospective controlled randomized study was performed on 100 patients undergoing elective laparoscopic cholecystectomy to evaluate the benefit of routine drainage in simple uncomplicated procedures. The 100 patients were randomized into two groups. Group 1 patients (n = 50) had a drain placed through the epigastric trocar site. The drain was removed before their discharge unless bile or blood was present. Group 2 patients (n = 50) did not have a drain placed. Eleven patients in group 2 (no drain) (22%) were discharged on the same day of surgery (within 8 h), and the remaining 89 patients in both groups were discharged the day after surgery (within 23 h). There were no wound infections or postoperative fever in either group. There were minor but not statistically significant differences between the two groups in postoperative severity and duration of abdominal pain, shoulder pain, and nausea. Furthermore, the two groups were similar in respect to postoperative recovery time and return to work. PMID- 7881143 TI - An initial experience with lighted ureteral catheters during laparoscopic colectomy. AB - Ureteral catheters are recommended when a difficult pelvic dissection is anticipated to minimize the risk of ureteral injuries. With the introduction of laparoscopic-assisted colectomy, it has become necessary to replace tactile with visual feedback. Lighted ureteral catheters (LUC) have been advocated for major laparoscopic pelvic surgery as a means of enhancing ureteral identification. However, the use of LUC has been anecdotal to this point. We present the first series of selectively used LUC during laparoscopic-assisted colectomy. Forty-nine consecutive laparoscopic-assisted colectomies were reviewed in which patients had LUC placed or not (NC) [LUC,24(49%); NC, 25(51%)]. Indications for catheter insertion included complicated diverticular disease, previous pelvic surgery, and obesity. The need for LUC was at the discretion of the surgeon. Data collected included catheter visualization, type of procedure, operative time, operating room cost, and catheter or ureteral complications. Catheters were visualized in 5 of 6 (83%) right colectomies and 15 of 18 (83%) left colectomies. Nonvisualization was because of migration to the bladder (2 cases) and dense inflammatory reaction (2 cases). No catheter complications or ureteral injuries occurred in either group. Operative time (LUC, 192 +/- 11.3 min, NC, 161.4 +/- 9.5 min) was significantly longer in the LUC group as a result of the time for catheter insertion and the greater complexity of the case. The operating room cost was similar in the two groups (LUC, $3488.63 +/- 259.01; NC, $3537.56 +/- 313.43). The results indicate that selected use of LUC does significantly increase operating time without significantly increasing operating room cost or operative morbidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881144 TI - The effects of intraperitoneal local anesthetic on analgesic requirements and endocrine response after laparoscopic cholecystectomy: a randomized double-blind controlled study. AB - This randomized double-blind placebo-controlled study was designed to evaluate the effects on postoperative pain of the local anesthetic, 0.5% bupivacaine with epinephrine, sprayed hepatodiaphragmatically under the surgeon's direct view during laparoscopic cholecystectomy. Metabolic endocrine responses to surgery (glucose and cortisol) and nonsteroidal anti-inflammatory drug requirements were investigated, as well as the presence of nausea, vomiting, and sweating. Local anesthetics or placebo solutions were given as follows. Immediately following the creation of a pneumoperitoneum, surgeons sprayed the first 20 mL of solution (S1), and an additional 20 mL of solution (S2) was sprayed at the end of the operation. Patients were classified into three groups (14 patients per group). Group A received 20 mL of saline during both S1 and S2, group B received 20 mL of saline during S1 and 20 mL of bupivacaine during S2, and group C received 20 mL of bupivacaine during both S1 and S2. The degree of postoperative pain was assessed using the visual analogue scale (VAS) and the verbal rating scale (VRS) on arrival in the recovery room and subsequently at time intervals of 4 h, 8 h, 12 h, and 24 h. The results of this study indicate a significant decrease of postoperative pain in patients treated with local anesthetic. VAS and VRS pain scores, as well as respiratory rate and analgesic requirements, were significantly lower in group C. The postoperative plasma cortisol level in group C was significantly lower than in groups A and B. PMID- 7881145 TI - Balloon dilatation of the sphincter of Oddi facilitates passage of glass beads from the canine biliary tract. AB - Laparoscopic management of common duct stones is increasing. The most widely used technique involves trans-cystic duct scope placement and stone extraction. Occasionally, stones cannot be retrieved and are allowed to pass spontaneously after manipulation of the sphincter of Oddi. This study examines a model of sphincter of Oddi dilatation in the dog to facilitate passage of glass beads simulating gallstones. In 24 dogs, glass beads of varying sizes (3-8 mm) were implanted in the gallbladder and allowed to pass spontaneously over 1 month. In three separate groups, these animals underwent (1) sham instrumentation of the sphincter of Oddi (control), (2) sphincter dilatation with balloon catheters, or (3) transduodenal sphincterotomy. At the end of 1 month, all the animals were autopsied, and the glass beads were retrieved. Histologic sections of the pancreas were examined for possible pancreatitis. The results of this study show that no animal experienced pancreatitis from sphincter manipulation or the passage of glass beads. The control animals who underwent sham manipulation of the sphincter passed 10% of their glass beads. In contrast, after sphincter dilatation, 52.5% of the 3-mm glass beads passed or 22% of all size beads. Animals with sphincterotomy passed a similar amount of glass beads as those with balloon dilatation. These studies suggest that balloon dilatation is as efficacious as sphincterotomy in facilitating the passage of glass beads from the canine biliary tract. PMID- 7881146 TI - The learning curve for laparoscopic cholecystectomy. AB - The introduction of laparoscopic cholecystectomy (LC) in 1987 has resulted in its wide acceptance by surgeons in the United States. Questions about proper training and learning curve for surgeons wishing to perform laparoscopic procedures have been raised during this period. We retrospectively evaluated 416 consecutive cholecystectomy cases that were performed by eight surgeons in a community teaching hospital. In this report, 374 patients had LC and 42 patients (10%) had an attempted LC, which had to be converted to an open cholecystectomy (CONV). Surgeons A and B performed 40% and 18% of all LC cases, respectively, and were classified as the surgeons with the highest volume of cases. Parameters, including conversion rate, operative time, and complications, were evaluated to define the learning curve. Surgeons A and B experienced 17% and 14% initial conversion rates for the first 35 cases, respectively. These rates dramatically dropped to an acceptable level (4% and 3%) with increased experience. The operative time for surgeon A for the first and last 35 cases improved from 97 +/- 25 min to 74 +/- 32 min (p = 0.01). Although the procedure time for surgeon B improved by 4 min, this difference was not statistically significant. The operative time for all cases was 81 +/- 31 min and 87 +/- 27 min, respectively, for surgeons A and B, which was significantly less than that for other surgeons (p = 0.01). A total of 12 patients experienced complications related to LC. Most of the complications (75%) occurred in the first 30 cases for all surgeons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881147 TI - Laparoscopic reversal of Hartmann procedure. AB - Laparoscopic surgery has expanded rapidly since the introduction of laparoscopic cholecystectomy. We have performed three laparoscopic Hartmann reversals in the last year and have compared these cases to eight open reversals. Laparoscopic technique has the advantage with regard to early oral intake, shortened length of stay, decreased blood loss, and decreased postoperative pain. Laparoscopic Hartmann reversal has comparable operative time with the open technique. We believe that laparoscopic Hartmann reversal should be considered by experienced laparoscopic surgeons. PMID- 7881148 TI - Endocoagulator control of the mesoappendix for laparoscopic appendectomy. AB - This article reports a new technique for laparoscopic appendectomy. The endocoagulator is used to effect sealing of the appendicular vessels, by heat, before their division. The technical steps are described. The results obtained from 30 cases prove its efficacy, safety, simplicity, and adaptability to varying clinical situations. The possible benefit of future nonadhesion formation is discussed. PMID- 7881149 TI - Laparoscopic and minilaparotomy Billroth I gastrectomy for gastric ulcer using an abdominal wall-lifting method. AB - Laparoscopic distal gastrectomy is still technically difficult because of the lack of appropriate techniques, the expensive laparoscopic instruments, and the use of numerous disposable stapling devices. In an attempt to solve these problems, we have designed a method of laparoscopic and minilaparotomy Billroth I gastrectomy using an abdominal wall-lifting method. PMID- 7881150 TI - Laparoscopic gastrectomy for obstructing duodenal ulcer. AB - A case of bilateral truncal vagotomy and antrectomy for pyloric stenosis is presented. Other procedures for laparoscopic treatment of peptic ulcer disease are discussed. PMID- 7881151 TI - Drainage of hepatic amebic abscess successfully treated by laparoscopy. AB - A case of hepatic amebic abscess is presented that was treated successfully by laparoscopy. The patient was fully worked up, including computed tomography (CT) scan, video-colonoscopy, and blood profiles. The laparoscopic surgical technique is fully discussed and proved to be a very useful tool in the management of this problem, obviating the need for a formal laparotomy and its potential complications. PMID- 7881152 TI - A safe simple method for removal of the gallbladder through the umbilical trocar site during laparoscopic surgery. PMID- 7881153 TI - Molecular regulation of iron proteins. AB - Cellular iron metabolism comprises pathways of iron-protein synthesis and degradation, iron uptake via transferrin receptor (TfR) or release to the extracellular space, as well as iron deposition into ferritin and remobilization from such stores. Different cell types, depending on their rate of proliferation and/or specific functions, show strong variations in these pathways and have to control their iron metabolism to cope with individual functions. Studies with cultured cells have revealed a specific cytoplasmic protein, called 'iron regulatory protein' (IRP) (previously known as IRE-BP or IRF), that plays a key role in iron homoeostasis by regulating coordinately the synthesis of TfR, ferritin, and erythroid 5-aminolevulinate synthase (eALAS). Present in all tissues analysed, IRP is identical with the [4Fe-4S] cluster containing cytoplasmic aconitase. Under conditions of iron chelation, IRP is an apo-protein which binds with high affinity to specific RNA stem-loop elements (IREs) located 5' of the initiation codon in ferritin and eALAS mRNA, and 3' in the untranslated region of TfR mRNA. At 5' sites IRF blocks mRNA translation, whereas 3' it inhibits TfR mRNA degradation. Both effects compensate for low intracellular iron concentrations. Under high iron conditions, IRP is converted to the holo-protein and dissociates from mRNA. This reverses the control towards less iron uptake and more iron storage. Iron can therefore be considered as a feedback regulator of its own metabolism. It has recently become evident that nitric oxide, produced by macrophages and other cell types in response to interferon-gamma, induces the IRE binding activity of IRF. Moreover measurements of the RNA-binding activity of IRP in tissue extracts may provide valuable information on iron availability. PMID- 7881154 TI - Iron-deficiency anaemia. AB - Iron-deficiency anaemia (IDA) is a common clinical problem throughout the world and an enormous public health problem in developing countries. The cornerstone of the laboratory identification of IDA is a low haemoglobin and serum ferritin concentration although a normal serum ferritin does exclude IDA. When the serum ferritin is normal in an anaemic patient with iron-deficient erythropoiesis, it is common practise to perform a bone marrow examination to diagnose IDA. The recent introduction of serum transferrin receptor measurements is a useful alternative for distinguishing IDA from the anaemia of chronic disease because the serum receptor concentration is usually elevated in patients with IDA but normal in patients with anaemia due to inflammation or neoplasia. It is helpful for the clinican to be aware of the causes of physiological IDA. The most important are increased rate of body growth, excessive menstrual blood loss, pregnancy, regular blood donation, intensive endurance training, chronic aspirin use and a vegetarian diet. Without these, a careful search for unsuspected gastrointestinal blood loss must be made and even when the suspicion of physiological IDA is high, it is prudent to screen for fecal occult blood. In most patients, IDA responds promptly to oral iron therapy. Patients who experience troublesome side-effects with oral iron might benefit from a gastric delivery system for oral iron which eliminates nausea and vomiting and improves iron absorption when given with food.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881155 TI - Prevention of iron deficiency. AB - This chapter discusses different methods to prevent iron deficiency--to reduce iron losses (e.g. reducing menstrual iron losses by using a contraceptive pill or combating of hookworm infestation) or to increase iron absorption. Iron absorption can be increased (1) by modifying the composition of meals--increasing the content of dietary factors enhancing iron absorption (e.g. meat and ascorbic acid) or reducing the content of factors inhibiting iron absorption such as phytate and iron-binding phenolic compounds, (2) by increasing the iron content of the diet by fortification with iron, or by (3) supplementation with iron tablets. Several factors to consider in the choice of strategy are discussed such as the importance of the bioavailability of the diet for the efficacy of iron fortification, the choice of vehicle for iron fortification that is compatible with the iron compound used, the feasibility to increase the bioavailability of the dietary iron by modification of the composition of the diet and the short time available in pregnancy to ensure a sufficient supply of the extra iron needed limiting the effective measures available to supplementation with iron tablets. PMID- 7881156 TI - Iron metabolism in inflammation. AB - Alteration in iron metabolism is one of the proposed mechanisms underlying the anaemia of inflammation and chronic disease, the most common disorder in hospitalized patients. Iron metabolism parameters in inflammatory disease are characterized by blockage of tissue iron release, decreased serum iron and total iron binding capacity and an elevated serum ferritin level, reflecting augmented ferritin synthesis as part of the acute-phase response. The altered iron metabolism in inflammation is proposed to be a part of the host defence mechanism against invading pathogens and tumor cells and is suggested to be mediated by inflammatory cytokines and NO. PMID- 7881157 TI - Sideroblastic anaemia. AB - The startling morphological abnormalities of sideroblastic anaemia contrasts our uncertainty about its cause. Studies are hampered by the fact that the abnormality resides in the dividing and differentiating erythroblast which is difficult to obtain pure and in large numbers, and in which many levels of metabolic control must coexist. Recent molecular biology approaches have confirmed abnormalities of erythroid delta-aminolaevulinic acid synthase as the cause of X-linked, pyridoxine-responsive sideroblastic anaemia and mitochondrial DNA deletions as the most common cause of congenital macrocytic sideroblastic anaemia. They have also identified a second X-linked sideroblastic anaemia locus linked to phosphoglycerate kinase and associated with ataxia. An association between sideroblastic anaemia and the use of an oral copper chelating agent has highlighted unexplained links between erythroid copper and iron metabolism. Management decisions in relation to pyridoxine treatment, iron reduction, family studies, genetic counselling and antenatal diagnosis have in recent years become of practical relevance to families with known cases of congenital sideroblastic anaemia and careful documentation of the clinical outcome of these cases and of other family members is invaluable. Parallel and integrated studies on the molecular biology of erythroid differentiation are revealing the range of possible controlling influences on erythroblasts and defining the circumstances for each, allowing studies on the cause of the most prevalent form of sideroblastic anaemia (the idiopathic acquired form) and those inherited forms that are not X-linked to be approached with a much clearer perspective. PMID- 7881158 TI - Clinical spectrum and management of haemochromatosis. AB - Haemochromatosis is one of the most common inborn errors of metabolism. In prospective epidemiological studies the frequency of haemochromatosis is 0.0037 (76/20333 subjects) for homozygotes which corresponds to a gene frequency of 0.061 and a frequency of heterozygotes of 0.115. Abnormality in liver function tests, weakness and lethargy, skin hyperpigmentation, diabetes mellitus, arthralgia, impotence and ECG abnormalities are the most frequent findings and symptoms at diagnosis. In recent years about 50% of patients were detected without having liver cirrhosis and 20% of patients did not have any symptoms and pathology except iron overload. Survival analyses in long-term studies showed that in the absence of cirrhosis and diabetes, iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. Patients with massive and long-lasting iron overload had a worse prognosis than those with less severe iron excess. Iron removal in general ameliorated liver disease, weakness and cardiac abnormalities, and also prevented the progression of endocrine alterations. Therapy, however, did not influence insulin-dependent diabetes. Most deaths in patients with hereditary haemochromatosis were caused by liver cancers which often occurred many years after complete iron removal. In patients with haemochromatosis, liver cirrhosis, cardiomyopathy, and diabetes mellitus are also significantly more frequent causes of deaths when compared with the general population. Further strategies have to evaluate the design of screening programmes in order to diagnose more patients in the precirrhotic and asymptomatic stage. PMID- 7881159 TI - Genetics of haemochromatosis. AB - This review is largely concerned with the frequency of genetic haemochromatosis (GH) and attempts to find the gene responsible. Studies of disease prevalence are reviewed along with the association of GH with other inherited disorders. The high prevalence of the disorder found in a number of surveys of populations of European origin along with the relatively few patients presenting with the clinical features of the advanced disease remains a paradox. The tight linkage between HLA-A and GH has been known since 1975 but it has not been possible to distinguish between a telomeric or centromeric location for the gene (HFE) relative to HLA-A. The recent explosion in detailed knowledge of the genetic map of the region telomeric of HLA-A on chromosome 6p has made it possible to examine new genetic markers. The very strong association between GH and D6S105-8 suggests a gene location telomeric to HLA-A. The lack of a precise location, and uncertainty about either the primary biochemical abnormality or the tissues involved has delayed the identification of the gene but expressed genes in the region around HLA-A are now being isolated and tested. PMID- 7881160 TI - Clinical manifestations and therapy of transfusional haemosiderosis. AB - Long-term blood transfusions lead to the accumulation of iron that in the absence of chelation therapy causes complications such as liver cirrhosis, growth failure, hypogonadism, hypothyroidism, hypoparathyroidism, diabetes and myocardiopathy. The last still represents the most frequent cause of death in haemosiderotic transfusion-dependent patients. At the moment the only chelator widely used is desferrioxamine (DFX). The drug works best when administered as a continuous infusion, mainly by the subcutaneous route. To patients with severe iron overload, impending organ failure, or poor compliance to chelation, DFX can be administered intravenously, through an externalized central catheter or, preferably, a subcutaneous port. Several studies have shown the effectiveness of DFX in reducing the iron burden, thus preventing the complications, once considered inevitable, of iron overload, and even in reverting some, but not all, of the iron-induced dysfunctions. Practical and psychological support are necessary to ensure satisfactory compliance with a therapy that is cumbersome and difficult. Toxic effects of DFX such as growth failure, hearing impairment and bone abnormalities seem to occur mainly in patients who have received high doses of DFX despite a low iron burden. Visual loss and renal and pulmonary toxicities, on the contrary, seem to be more directly related to high DFX peak doses administered irrespective of the patient's amount of iron overload. After bone marrow transplantation, phlebotomy or erythrocytoapheresis might be necessary to reduce further the iron accumulated during years of transfusions. PMID- 7881161 TI - Oral iron-chelating therapy: the L1 experience. AB - L1 is the most widely studied oral iron-chelating drug and at present the only one shown to be effective at causing negative iron balance in long-term clinical trials for thalassemia major and other transfusion-dependent refractory anaemias. Because of side-effects, both in experimental animals and in humans, its development as a widely available pharmaceutical agent has been delayed. However, for the large numbers of transfusion-dependent, iron-overloaded patients who do not use DFX because of poor compliance, adverse effects or unavailability of the drug, L1 may be a suitable alternative for iron chelation. However, its use should be restricted to Ethical Committee approved clinical trials. Patients who are capable of using DFX effectively should be encouraged to continue doing so until an oral iron chelator has been fully established for clinical use. It is hoped that 3-hydroxypyrid-4-one analogues of L1 as well as compounds related to pyridoxal isonicotinyl hydrazone, HBED or hydroxamic acid can be found both orally effective and safe for long-term administration. Current and future trials of L1 could address some of the following issues, beside extending present studies on the efficacy and adverse effects of L1: 1. The effect of administering a reduced dose of L1 (< 75 mg/kg per day) on the incidence of adverse effects and on long-term efficacy. 2. The efficacy and adverse effects of L1 at a low dose in patients with non-transfusional iron overload such as thalassaemia intermedia, primary haemochromatosis and congenital haemolytic anaemias. 3. The effect of combining oral L1 with intravenous or subcutaneous DFX on the incidence of adverse effects and efficacy. 4. Elucidation of the mechanisms involved in agranulocytosis and joint toxicity and finding methods to predict for individual susceptibility to these adverse effects and ways of preventing them. PMID- 7881162 TI - Control of disease by selective iron depletion: a novel therapeutic strategy utilizing iron chelators. AB - Recognition of the central role of iron in the generation of toxic, oxygen derived species through the Haber-Weiss reaction, the ability of desferrioxamine (DFX) to prevent the damage associated with free radical generation in reperfusion injury, and its inhibitory effect on cell proliferation by inactivation of the iron dependent enzyme ribonucleotide reductase, resulted in an increasing number of studies exploring the novel therapeutic applications of iron chelating drugs: (a) Animal models of reperfusion injury have shown that DFX is able to decrease post-anoxic damage to the brain and heart as manifested in decreased infarct size and improved functional recovery. Iron chelators may be particularly useful in improving the preservation of organs intended for transplantation such as the heart, lung or kidney. (b) Anthracycline cardiotoxicity is aggravated by iron and inhibited by iron chelators. Because the mechanism of its antineoplastic effect differs from its cardiotoxic effect, it is possible to inhibit anthracycline cardiotoxicity without interfering with therapeutic efficacy. In vivo and in vitro animal studies have yielded encouraging results but much additional experimental work is still required before iron chelating therapy may be advocated for use in patients on anthracycline therapy. (c) Cell proliferation can be inhibited by iron chelators through the reversible inhibition of ribonucleotide reductase, a rate-limiting enzyme in DNA synthesis. This may be exploited for the treatment of malignant disease, and preliminary studies have already shown that DFX in combination with multidrug chemotherapy is effective in controlling neuroblastoma and other tumours. However, the contribution of DF to the overall clinical effect is unclear. Prospective controlled clinical studies are required in order to establish whether the antiproliferative, or cell synchronizing properties of DFX may be of practical usefulness in the control of malignant disease. (d) Control of protozoal infection: Experimental in vivo and in vitro models have shown that malarial infection may be inhibited by iron chelating therapy. This useful effect of DFX and other iron chelators is most probably related to ribonucleotide reductase inhibition. Clinical studies of asymptomatic P. falciparum malaria and of cerebral malaria have shown both an accelerated rate of parasite clearance and earlier recovery from coma. These observations lend new meaning to the term 'nutritional immunity' and open new channels for exploring the possibility of controlling infection by means of selective intracellular iron deprivation. Experimental models for studying the effect of iron chelators on other intracellular pathogens such as Toxoplasma gondii, Chlamydia psittaci, or Mycobacterium tuberculosis should be established.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7881163 TI - [14th Oncology meeting. Paris, May 30-June 1, 1994. Abstracts]. PMID- 7881164 TI - A compilation and classification of DNA binding sites for protein transcription factors from vertebrates. AB - The field of protein transcription regulators and their DNA sequence specificity has been the most rapidly expanding in the last few years. The concerted interplay of protein transcription factors on the regulatory regions of eukaryotic genes (promoters, enhancers, origins of replication, silencers, and matrix-attached regions) regulates transcription levels; the differential activity of genes during development and the cell cycle, between cell types, and in response to physiological stimuli results from interdigitation of regulatory circuits controlling transcription initiation, finely tuned by the relative amounts of protein factors synthesized in a cell type, their phosphorylation, isoforms within factor families, the way protein regulators are brought in contact with one another through the patchwork of their cognate sites on the regulatory regions of genes, and by regulation of their nuclear import. The varying affinity of the same factor for its cognate DNA in different promoters can also be modulated by the type of proteins it is brought into contact with, by one or more nucleotide changes in its binding sites among promoters, and by the chromatin structure. The classification of protein transcriptional regulators attempted here according to their DNA binding specificity into those that bind AT , GC-, GA, TG-rich and mixed motif has one obvious advantage: different protein factors that bind to the same DNA sequence will be found within the same class. In addition, this classification has allowed us to discern a class of transcriptional regulators whose binding site consists of a GA- and a CT-rich moiety; no other two pairs of dinucleotides compose a major class of factor sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881165 TI - Control of tumor necrosis factor gene expression. AB - This review summarizes the known data about transcriptional control of the tumor necrosis factor genes. Mechanisms of transcriptional induction of TNF gene expression and the influences of regulatory elements in the promter and in the 3' flanking regions are discussed. Posttranscriptional events that influence regulation of TNF gene expression such as destabilization of mRNA are described. The influence of chromatin structure and possible functional implications are also reported. Although their biological effects largely overlap, it is concluded that the TNF alpha and TNF beta genes are differently regulated at the transcriptional level. PMID- 7881166 TI - Expression of the BMP 2 gene during bone cell differentiation. AB - Bone morphogenetic protein 2 (BMP 2) and transforming growth factor beta (TGF beta) are actively involved in bone formation and remodeling. TGF beta, a powerful stimulant in the early stage of bone cell growth and matrix formation, inhibits differentiation and in vitro mineralized nodule formation in primary fetal rat calvarial osteoblast system. TGF beta also negatively regulates BMP 2 expression at the transcriptional level. BMP 2 gene expression is controlled by a battery of transcriptional factors, some known and some yet to be identified. Immortalized osteoblast cell lines generated from a transgenic mouse carrying BMP 2 promoter-driven SV40 large T antigen transgene are described as powerful tools for studying regulation of BMP 2 gene expression and bone cell differentiation at the molecular level. PMID- 7881167 TI - Galectins: conservation of functionally and structurally relevant amino acid residues defines two types of carbohydrate recognition domains. PMID- 7881168 TI - Core fucosylation in honeybee venom. PMID- 7881169 TI - Mammalian alpha-mannosidases--multiple forms but a common purpose? AB - Previously, alpha-mannosidases were classified as enzymes that process newly formed N-glycans or degrade mature glycoproteins. In this review, we suggest that two endoplasmic reticulum (ER) alpha-mannosidases, previously assigned processing roles, have important catabolic activities. Based on new evidence, we propose that the ER/cytosolic mannosidase is involved in the degradation of dolichol intermediates that are not needed for protein glycosylation, whereas the soluble form of Man9-mannosidase is responsible for the degradation of glycans on defective or malfolded proteins that are specifically retained and broken down in the ER. The degradation of oligosaccharides derived from dolichol intermediates by ER/cytosolic mannosidase now explains why cats and cattle with alpha mannosidosis store and excrete some unexpected oligosaccharides containing only one GlcNAc residue. Similarly, the action of ER/cytosolic mannosidase, followed by the action of the recently described human lysosomal alpha(1 --> 6) mannosidase, together explain why alpha-mannosidosis patients store and excrete large amounts of oligosaccharides that resemble biosynthetic intermediates, rather than partially degraded glycans. The relative contributions of the lysosomal and extra-lysosomal catabolic pathways can be derived by comparing the ratio of trisaccharide Man beta (1 --> 4)GlcNAc beta (1 --> 4)GlcNAc to disaccharide Man beta (1 --> 4)GlcNAc accumulated in tissues from goats with beta mannosidosis. A similar determination in human beta-mannosidosis patients is not possible because the same intermediate, Man beta (1 --> 4)-GlcNAc is a product of both pathways. Based on inhibitor studies with pyranose and furanose analogues, alpha-mannosidases may be divided into two groups. Those in Class 1 are (1 --> 2) specific enzymes like Golgi mannosidase I, whereas those in Class 2, like lysosomal alpha-mannosidase, can hydrolyse (1 --> 2), (1 --> 3) and (1 --> 6) linkages. A similar classification has recently been derived by others from protein sequence homologies. Based on this new classification of the alpha mannosidases, it is possible to speculate about their probable evolution from two primordial genes. The first would have been a Class 1 ER enzyme involved in the degradation of glycans on incompletely assembled or malfolded glycoproteins. The second would have been a Class 2 lysosomal enzyme responsible for turnover. Later, other alpha-mannosidases, with new processing or catabolic functions, would have developed from these, by loss or gain of critical insertion or retention sequences, to yield the full complement of alpha-mannosidases known today. PMID- 7881170 TI - Glycosylation of human trophoblast integrins is stage and cell-type specific. AB - Cytotrophoblasts are the specialized epithelial cells of the placenta. During the first trimester, a subpopulation of chorionic villus cytotrophoblasts differentiates along an invasive pathway and penetrates the maternal endometrium, decidua and spiral arterioles. Cytotrophoblast invasiveness declines rapidly during the second half of gestation. Isolated cytotrophoblasts of different gestational ages retain this differential invasiveness in culture. To determine whether the properties of integrin receptors for extracellular matrix molecules differ between invasive and non-invasive cytotrophoblasts, detergent extracts of isolated cytotrophoblasts of different gestational ages, and of first-trimester villous fibroblasts, were immunoprecipitated with subunit-specific anti-beta 1 integrin antibodies. Striking alterations in electrophoretic mobility were observed in beta 1 integrins from first-trimester cytotrophoblasts, as compared with those from term cytotrophoblasts or first-trimester villous fibroblasts, suggesting a cell-type-specific, temporally regulated alteration in glycosylation. Treatment of total first-trimester cytotrophoblast beta 1 integrins or the isolated alpha 5/beta 1 fibronectin receptor with endo-beta galactosidase restored electrophoretic mobility to control levels, suggesting the presence of polylactosamine-bearing oligosaccharides. Further analysis by enzyme digestion and lectin-affinity chromatography suggested that they consisted of at least three antennae and short, sialylated lactosamine units. These oligosaccharides did not affect the affinity of the first-trimester cytotrophoblast fibronectin receptor for fibronectin. However, this receptor bound more strongly to wheat germ agglutinin than control fibronectin receptor and resisted elution by high concentrations of sugar hapten, requiring ionic detergent for removal. These results suggested that the altered glycosylation affected the conformation of the fibronectin receptor. PMID- 7881171 TI - Enzymatic synthesis of two lacto-N-neohexaose-related Lewis x heptasaccharides and their separation by chromatography on immobilized wheat germ agglutinin. AB - Radiolabelled lacto-N-neohexaose was fucosylated with partially purified alpha (1,3)fucosyltransferase(s) from human milk. Structural analysis of the monofucosylated products obtained at an early stage of the reaction revealed that both distal branches of the acceptor had reacted equally well, generating Lewis x determinants, while the reducing end glucose had not reacted. The two isomeric Lewis x glycans were readily separated from each other by chromatography on immobilized wheat germ agglutinin (WGA), because alpha (1,3)fucosylation of the (1 --> 6)-linked branch of lacto-N-neohexaose was associated with a dramatic loss of WGA affinity. The fucosylation mixture of lacto-N-neohexaose also contained a difucosylderivative that carried Lewis x determinants at both distal branches. Attempted refucosylation of this octasaccharide failed to transfer fucose to the glucose unit. PMID- 7881172 TI - Glycans as targets for monoclonal antibodies that protect rats against Trichinella spiralis. AB - We have investigated the role of glycans on Trichinella spiralis antigens in recognition by rat monoclonal antibodies (mAbs) which protect rat pups against challenge with the parasite. In pups born to infected dams or pups passively immunized with mAbs, antibodies eliminate a challenge dose from the intestine within hours ('rapid expulsion'). Because such dramatic protection can be afforded by mAbs, we have sought to characterize the parasite antigens they target. In this report we show that protective antibodies were unable to bind excretory/secretory (ES) antigens deglycosylated with trifluoromethanesulphonic acid (TFMS). In addition, oligosaccharides isolated from glycoproteins by alkaline hydrolysis or peptide: N glycosidase F (PNGase F) digestion were bound by protective, but not non-protective, mAbs. Glycans affinity purified with protective mAb 9D bound to all but one protective mAb. These antibodies have been shown previously to bind to the surfaces of intact larvae, indicating that the glycan is exposed on the parasite surface. Candidate glycans that may be involved in binding protective mAbs have unusual tri- and tetra-antennary structures with terminal tyvelose moieties (Reason et al., Glycobiology, 4, 000-000, 1994). Coating of the larval surface with such glycans may serve to protect the parasite and its secreted products from enzymatic attack as the parasite travels to and resides in its epithelial niche. PMID- 7881173 TI - Novel tyvelose-containing tri- and tetra-antennary N-glycans in the immunodominant antigens of the intracellular parasite Trichinella spiralis. AB - The larval stage of the intestinal nematode, Trichinella spiralis, secretes and displays on its cuticle a number of antigenically cross-reactive glycoproteins. These so-called TSL-1 antigens induce a powerful antibody response in parasitized animals. In rats, anti-TSL-1 antibodies mediate a protective immunity that expels invading larvae from the intestine. The vast majority of anti-TSL-1 antibodies are specific for glycans. Although the biological functions of TSL-1 antigens are not known, the powerful effect of glycan-specific antibodies on the intestinal survival of T. spiralis suggests that they play an important role in parasite establishment. Little is known about the structures of the glycans present on the TSL-1 glycoproteins. Recent studies have suggested, however, that the antigens contain very unusual glycans (Wisnewski, N., McNeil, M., Grieve, R.B. and Wassom, D.L., Mol. Biochem. Parasitol., 61, 25-36, 1993). Sugar and linkage analysis of the combined secreted products unexpectedly showed that a major terminal sugar is tyvelose (3,6-dideoxy-D-arabino-hexose; Tyv) which has previously been found only in certain gram-negative bacterial lipopolysaccharides. In this paper, we report the first rigorous structural study of oligosaccharides released from TSL-1 antigens by peptide N-glycosidase F digestion. Using strategies based on fast atom bombardment mass spectrometry (FAB-MS), we have discovered a novel family of tri- and tetra-antennary N-glycans whose antennae are comprised of the tyvelose capped structure: Tyv1,3GalNAc beta 1,4(Fuc alpha 1,3)GlcNAc beta 1-. Thus a major population of TSL-1 glycans contains clusters of hydrophobic terminal structures which are likely to be highly immunogenic. PMID- 7881174 TI - Structure of the major neutral oligosaccharide-alditols released from the egg jelly coats of Axolotl maculatum. Characterization of the carbohydrate sequence GalNAc(beta 1-4)[Fuc(alpha 1-3)] GlcNAc(beta 1-3/6). AB - Several O-linked oligosaccharides of the jelly coat surrounding the eggs of Axolotl maculatum were analysed by 1H-NMR spectroscopy. The four major oligosaccharidealditols released by reductive beta-elimination display either the Lewisx (Lex) determinant or the sequence GalNAc(beta 1-4)[Fuc(alpha 1-3)]GlcNAc. This last structure has previously been characterized in allergenically active oligosaccharides isolated from the sea squirt H-antigen, and in the N-linked glycans of Schistosoma mansoni and human urokinase. It represents the major carbohydrate chain found in A. maculatum, the oviduct of which constitutes an excellent source of beta 1-4-acetylgalactosaminyl transferase activity. Moreover, the carbohydrate chains isolated from A. maculatum are quite different from those found in seven other amphibian species, in which the presence of species-specific material has been characterized. The role of carbohydrates appears more and more apparent during the fertilization process, and the diversity of the O-linked oligosaccharides supports such a biological role. PMID- 7881175 TI - Purification and characterization of alpha-L-fucosidase from Chinese hamster ovary cell culture supernatant. AB - In this study, alpha-L-fucosidase from Chinese hamster ovary (CHO) cell culture supernatant was purified 11 200-fold to apparent homogeneity to assess the rate of fucose hydrolysis from oligosaccharide and glycoprotein substrates. The fucosidase migrated as a single band of 51 kDa on SDS-PAGE and is a glycoprotein, as determined by retention on concanavalin A-Sepharose, and by lectin blotting with concanavalin A. Hydrolysis of the artificial substrate 4-methyl-umbelliferyl alpha-L-fucoside (4MU-Fuc) followed simple Michaelis-Menten kinetics, and was competitively inhibited by free fucose and by two known fucosidase inhibitors, fucosylamine and deoxyfuconojirimycin. Hydrolysis of fucose from oligosaccharides including 2'-fucosyllactose, 3-fucosyllactose, Fuc alpha(1,6)GlcNAc and pooled gp120 oligosaccharides with the Fuc alpha(1,6)GlcNAc linkage also followed simple Michaelis-Menten kinetics. However, activity toward 4MU-Fuc was optimal near pH 7, while activities toward the oligosaccharide substrates were optimal near pH 5. No fucose was released from the recombinant CHO cell-produced glycoproteins gp120 or soluble CD4 with the Fuc alpha(1,6)GlcNAc linkage, or from human serum alpha 1 acid glycoprotein with the Fuc alpha(1,3)GlcNAc linkage. Enzymatic removal of sialic acid and galactose from gp120 oligosaccharides did not alter the susceptibility of gp120 to fucosidase attack. These data suggest that released CHO cell fucosidase does not contribute to the heterogeneity of fucosylation that has been observed in CHO cell culture-produced glycoproteins. PMID- 7881176 TI - Change in glycosylation of chicken transferrin glycans biosynthesized during embryogenesis and primary culture of embryo hepatocytes. AB - Transferrins were isolated by immunoaffinity chromatography from chicken serum, chicken embryo serum and from the culture medium of chicken embryo hepatocytes in primary culture. The glycovariants of these three transferrins were separated by ion-exchange chromatography using a fast protein liquid chromatography (FPLC) system. The structures of the oligosaccharide-alditols released by hydrazinolysis from the glycovariants were compared after analysis by a combination of methanolysis, methylation analysis and 1H-NMR spectroscopy. In the three transferrins analysed, the oligosaccharides were of the biantennary N acetyllactosaminic type, having several prominent features. In particular, the embryo serum transferrin glycan differed from that of chicken serum transferrin by the presence of a bisecting N-acetylglucosamine, suggesting a developmental change in glycosylation. The glycan structure of the transferrin secreted by the embryo hepatocytes in primary culture was marked by the presence of fucose (alpha 1-6) linked to the core N-acetylglucosamine, suggesting that expression of the fucosyltransferase activity is dependent on cell culture conditions. Moreover, comparative analysis of chicken serum transferrin and ovotransferrin glycans reinforces the idea that the glycosylation of two identical polypeptide chains is organ specific. PMID- 7881177 TI - Sialylation of n-alkyllactosides, galactosides and glucosides by sialyltransferases from rat liver Golgi vesicles. AB - n-Alkyl alpha- and beta-lactosides, galactosides and glucosides with different alkyl chain lengths (C2, C8, C14 and C20) were synthesized and used as acceptors for sialyltransferases from rat liver Golgi vesicles. The beta-galactosides, beta glucosides, and both alpha- and beta-lactosides, were sialylated. Keeping the acceptor concentration constant, sialylation rates reached a maximum for the n octyl alpha- and beta-lactosides, n-octyl beta-galactoside and n-octyl beta glucoside, respectively. n-Octyl alpha-galactoside and n-octyl alpha-glucoside were not sialylated. The reaction products were characterized by TLC. With n octyl lactoside and galactoside as acceptors, two major sialylation products were formed. They could be separated by preparative TLC, and their structures were identified as 2-3 and 2-6 sialylated acceptors, respectively, by a combination of periodate oxidation, NaBD4 reduction, permethylation and subsequent analysis by fast atom bombardment mass spectrometry (FAB-MS). The structure of the single product obtained from n-octyl beta-glucoside was determined to be the 2-6 sialylated glucoside. Competition experiments with n-octyl lactoside and lactosylceramide and ganglioside Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1Cer (GM1) as acceptors for sialyltransferases suggested that SAT-I [NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1Cer (GM3) synthase] was at least in part responsible for the 2-3 sialylation of n-octyl lactoside. PMID- 7881179 TI - Identification and characterization of a UDP-GalNAc:GlcNAc beta-R beta 1-->4-N acetylgalactosaminyltransferase from cercariae of the schistosome Trichobilharzia ocellata. Catalysis of a key step in the synthesis of N,N'-diacetyllactosediamino (lacdiNAc)-type glycans. AB - Three different stages of the avian schistosome Trichobilharzia ocellata appeared to contain a novel N-acetylgalactosaminyltransferase activity. To investigate its function in the biosynthesis of schistosome glycoconjugates, the enzyme was partially purified from cercariae, a free-living stage of the parasite, by affinity chromatography on UDP-Sepharose. Acceptor specificity studies showed that the enzyme catalyses the transfer of N-acetylgalactosamine (GalNAc) from UDP GalNAc to oligosaccharides, glycopeptides and glycoproteins carrying a terminally beta-linked N-acetylglucosamine (GlcNAc) residue, regardless of the underlying structure. Analysis of the products obtained with GlcNAc and a desialylated and degalactosylated diantennary glycopeptide by 400 MHz 1H-NMR spectroscopy revealed that a GalNAc beta 1-->4GlcNAc (N,N'-diacetyllactosediamine,lacdiNAc) unit was formed. The enzyme can therefore be described as a UDP-GalNAc:GlcNAc beta-R beta 1-->4-N-acetylgalactosaminytransferase (beta 4-GalNAcT). Using specific acceptors, the enzyme could be distinguished from all other beta 4-GalNAcTs described to date, including the one from pituitary gland that is involved in the specific glycosylation of pituitary glycohormones. By contrast, the enzymatic properties of the schistosome beta 4-GalNAcT (except for the sugar-donor specificity) strongly resemble those of the beta 4-galactosyltransferase of higher animals, an enzyme which is known to control the synthesis of Gal1- >4GlcNAc (lacNAc)-type oligosaccharide chains. By analogy, the beta 4-GalNAcT is concluded to control the key step in the synthesis of lacdiNAc-type chains. LacdiNAc-type glycans are also common to the mollusc Lymnaea stagnalis, which is the intermediate host of T.ocellata. It is proposed that the schistosome beta 4 GalNAcT functions in the expression of specific carbohydrate structures that contribute to a molecular mimicry, enabling the schistosome to evade the defence system of the snail host. PMID- 7881178 TI - Structural studies of the N-linked sugar chains of human rhodopsin. AB - Human rhodopsin is a glycoprotein containing two N-linked sugar chains. After the isolation and purification of rhodopsins from human retinas, structural studies of their N-linked sugar chains were performed. The sugar moieties, quantitatively released as oligosaccharides from the polypeptide backbone by hydrazinolysis, were converted to radioactive oligosaccharides by reduction with NaB3H4 after N acetylation. As indicated by high-voltage paper electrophoresis, > 96% of the sugar chains were free of sialic acid and the remaining were sialylated derivatives. Structural studies of each oligosaccharide by lectin affinity column chromatography, and sequential exoglycosidase digestion in combination with methylation analysis, revealed that almost all of the oligosaccharides were hybrid-type sugar chains. While the major oligosaccharide species of bovine and human rhodopsin are identical, in contrast to the sugar chains of bovine rhodopsin, human rhodopsin also contains sialylated isomers and a high concentration of a galactosylated isomer. These results suggest that species specific processing of the sugar chains of rhodopsin occurs. PMID- 7881180 TI - Advances in the use of biotinylated diaminopyridine (BAP) as a versatile fluorescent tag for oligosaccharides. AB - We recently described a novel fluorescent compound, 2-amino,6-amidobiotinyl pyridine (BAP), that allows the tagging of oligosaccharides, their fractionation by reversed-phase HPLC with picomole scale detection, and the formation of functional neoglycoprotein equivalents with (strept) avidin for the detection of receptors and the generation of monospecific antibodies (Rothenberg et al., Proc. Natl Acad. Sci. USA, 90, 11939-11943, 1993). Here, we describe the enhancement of this approach by the following. (i) A simple one-step purification of BAP from its synthetic precursors and other reactants. (ii) Development of HPLC sizing column methods to quickly purify BAP-coupled oligosaccharides away from free BAP and other reactants. (iii) Development of anion-exchange and amine-adsorption HPLC procedures for the fractionation of BAP-oligosaccharide adducts by charge and size, respectively. (iv) Investigation of the affinity of BAP oligosaccharides for (strept)avidin, confirming the formation of stable complexes. (v) The use of BAP for sensitive monosaccharide compositional analysis of glycoproteins. (vi) Formation of stable BAP adducts without reduction and its implications for the mechanism of adduct formation. These advances make available a multitude of techniques for the fractionation of BAP-coupled oligosaccharides based on several different physical parameters. Distinct species of BAP-coupled oligosaccharides can be isolated and subjected to detailed structural analysis. Such defined molecules form stable complexes with streptavidin that are effectively neoglycoproteins, which can be used in a variety of biological applications. Notably, all of these approaches require relatively inexpensive materials and conventional equipment available in most laboratories. PMID- 7881181 TI - Sialylation and malignant potential in tumour cell glycosylation mutants. AB - Somatic mutations and drugs that either reduce beta 1-6GlcNAc-branching of N linked oligosaccharides or block the addition of terminal sequences containing galactose and sialic acid have been shown to inhibit tumour growth and metastasis. In an attempt to further define the oligosaccharide sequences that contribute to the malignant phenotype, we have selected spontaneous wheat germ agglutinin-resistant (WGAR) mutants from highly metastatic murine lymphoid tumour cells and characterized four mutant phenotypes. Mutants were selected from VM4, a clone of the MDAY-D2 tumour cell line which had been transfected with the bacterial beta-galactosidase gene (LacZ). VM4 cells retained the malignant phenotype of MDAY-D2 and the cells expressed LacZ, which facilitated the counting of metastases as the tumour cells stained blue when incubated with 5-bromo-4 chloro-3-indolyl beta-D-galactopyranoside (X-gal). The most frequently isolated mutant was defective in the transport of UDP-Gal into the Golgi, and as previously observed for this mutation, the cells were non-metastatic and produced very slow-growing solid tumours. Mutants expressing CMP-SA hydroxylase, and consequently glycoconjugates with N-glycolylneuraminic acid (NeuNGc), remained highly metastatic, but grew more slowly than VM4 cells as s.c. tumours in mice. A novel WGAR mutant showing a large increase in Gal beta 1-4GlcNAc:alpha 2-6 sialyltransferase (SA-T) mRNA levels (ST6N) and enzyme activity was observed to be less metastatic and also grew more slowly at the s.c. site of inoculation. Finally, a fourth phenotypic class of WGAR mutants showed a complex phenotype including expression of a beta Gal-binding cell surface lectin and reduced sialylation of glycoconjugates. These results suggest that changes in either the amount, the type or linkage of sialic acid in tumour cell glycoconjugates can affect tumour growth and metastasis. PMID- 7881182 TI - Purification and characterization of CMP-N-acetylneuraminic acid hydroxylase from pig submandibular glands. AB - N-Glycoloylneuraminic acid (Neu5Gc) is synthesized as its CMP-glycoside by the action of CMP-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase. This enzyme is a soluble cytochrome b5-dependent monooxygenase and has been purified to apparent homogeneity from pig submandibular glands by precipitation with N-cetyl-N,N,N trimethylammonium bromide and fractionation on Q-Sepharose, Cibacron Blue 3GA Agarose, Reactive Brown 10-Agarose, Hexyl-Agarose and Superose S.12. This procedure resulted in an 8960-fold purification of the hydroxylase with a recovery of 0.8%. The molecular mass of this protein was shown to be 65 kDa on SDS-PAGE and approximately 60 kDa as determined by gel filtration on Superose S.12, which suggests that the enzyme is a monomer. The purified CMP-Neu5Ac hydroxylase is activated by FeSO4 and inhibited by iron-binding reagents such as o-phenanthroline, KCN, Tiron and ferrozine. An apparent Km of 11 microM was determined for the substrate CMP-Neu5Ac using purified hydroxylase in the presence of Triton X-100-solubilized microsomes. In a reconstituted system consisting of purified hydroxylase, cytochrome b5, cytochrome b5 reductase and catalase, an apparent Km of 3 microM was measured. The apparent Km for cytochrome b5 in this system was 0.24 microM. Immunization of a rabbit with enriched and purified hydroxylase led to an antiserum that inhibited CMP-Neu5Ac hydroxylase activity and reacted with the purified 65 kDa protein on a Western blot after SDS PAGE. Antibodies specific for this 65 kDa protein were isolated and showed a strong reaction with the purified CMP-Neu5Ac hydroxylase from mouse liver after immunoblotting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881183 TI - Patterns of uronosyl epimerization and 4-/6-O-sulphation in chondroitin/dermatan sulphate from decorin and biglycan of various bovine tissues. AB - Dermatan sulphate is a co-polymer of two types of disaccharide repeats: D glucuronate-N-acetylgalactosamine and L-iduronate-N-acetylgalactosamine. The former can be O-sulphated at C-4 or C-6 of the galactosamine, whereas the latter contains almost exclusively 4-O-sulphated galactosamine. A minor proportion of the L-iduronate may be O-sulphated at C-2. Chondroitin sulphate has no L iduronate-containing repeats. We have used our recently developed methods for sequence analysis of galactosaminoglycans to investigate the structure of dermatan/chondroitin sulphates of the proteoglycans decorin and biglycan derived from various bovine tissues, like dermis, sclera, tendon, aorta, cartilage and bone. The glycan chains, radioiodinated at the reducing end, were partially cleaved with specific enzymes (chondroitin lyases), and subjected to high resolution polyacrylamide gel electrophoresis, blotting and autoradiography to identify fragments extending from the labelled reducing end to the point of cleavage. We used chondroitin B lyase to identify the location of L-iduronate, chondroitin AC-I lyase to locate D-glucuronate and chondroitin C lyase to cleave where D-glucuronate residues were succeeded by 6-O-sulphated N acetylgalactosamine. We could demonstrate tissue-specific, periodic and wave-like patterns of distribution for the two epimeric uronic acids, as well as specific patterns of sulphation in dermatan sulphates derived from either decorin or biglycan. For example, some dermatan sulphates contained D-glucuronate-rich domains that were always 6-sulphated (scleral decorin), others were always 4 sulphated (decorin from bovine dermis, cartilage and bone; biglycan from aorta) or 6-sulphated near the linkage region, but 4-sulphated in more distal domains (decorin from porcine dermis and bovine tendon). Decorin from bone and articular cartilage, as well as biglycan from articular and nasal cartilage, carried largely chondroitin sulphate chains, but also some dermatan sulphate, whereas galactosaminoglycan chains derived from aggrecan of nasal cartilage were free of L-iduronate. Decorin and biglycan from the same tissue (articular cartilage or sclera) had similar glycan chains. The two side chains in a biglycan molecule are probably also similar to one another. The portion of the glycan chains nearest to the core protein was substituted with charged groups to a variable degree, which may correlate with the structural features of the main chain. PMID- 7881184 TI - Production, purification and characterization of recombinant yeast processing alpha 1,2-mannosidase. AB - The Saccharomyces cerevisiae processing alpha 1,2-mannosidase, which trims Man9GlcNAc to Man8GlcNAc, has a lumenally oriented catalytic domain and an N terminal transmembrane domain. To obtain sufficient protein to study the structure and mechanism of action of this enzyme, the sequence encoding the catalytic domain was inserted downstream of the alpha-factor promoter and signal peptide in a high-copy vector for expression in S. cerevisiae as a secreted protein. Using oligosaccharide substrate (Glc1Man9GlcNAc or Man9GlcNAc), the medium of cells transformed with this plasmid showed an increase in alpha mannosidase activity that was directly related to the increase in cell density, whereas no alpha-mannosidase activity was detected in cells transformed with vector alone. SDS-PAGE of the medium showed the presence of a doublet of 63 and 60 kDa that was revealed by Coomassie Blue staining and by Western blotting with antibodies to the endogenous solubilized alpha-mannosidase. The recombinant alpha mannosidase was present in the medium at a level of approximately 1 mg/l and was purified in a single step by chromatography on S-Sepharose. High-resolution 1H NMR analysis of the Man8GlcNAc formed from Man9GlcNAc in the presence of the recombinant enzyme proved that it retained its specificity and removed only one specific alpha 1,2-mannose residue of the alpha 1,3 branch. Endoglycosidase H treatment decreased the molecular mass of both components of the doublet by approximately 5 kDa, showing that the heterogeneity is not due to differential N glycosylation. EDTA inhibited the activity of the recombinant enzyme, but the inhibition was reversed by the addition of divalent cations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881185 TI - Regulation of N-linked glycosylation. Neuronal cell-specific expression of a 5' extended transcript from the gene encoding N-acetylglucosaminyltransferase I. AB - A key transferase in the generation of mature N-linked carbohydrates is the medial Golgi enzyme N-acetylglucosaminyltransferase I (EC 2.4.1.101; GlcNAc-TI) which is encoded by the Mgat-1 gene. Previous studies revealed two size classes of Mgat-1 mRNA that are differentially expressed in mouse tissues. Nearly all tissues possess a shorter form (approximately 2.9 kb), whereas brain has predominantly a longer Mgat-1 mRNA (approximately 3.3 kb). We now show, by in situ hybridization of horizontal sections of adult mouse brain, that Mgat-1 RNA levels vary markedly in different brain cell types with the greatest expression being in neuronal cells. The differential expression of the approximately 2.9 kb and approximately 3.3 kb Mgat-1 mRNAs is likely to be controlled by tissue specific promoters since the size difference between the mRNAs was found to residue entirely in the 5' untranslated region of the approximately 3.3 kb mRNA. Evidence for this was obtained by an RNase H strategy, reverse transcription polymerase chain reaction (RT-PCR) and 5' anchored PCR. All of the 0.4 kb difference in size was localized upstream of the previously isolated cDNA sequence. Sequence information from this region was obtained from a mouse brain cDNA library by a PCR amplification strategy and a probe specific for the 3.3 kb mRNA was generated. This probe hybridized uniquely to the approximately 3.3 kb Mgat-1 mRNA and Southern blot analysis showed that the new sequence is physically linked to the Mgat-1 gene. A tissue culture model which displays an increase in expression of the approximately 3.3 kb Mgat-1 mRNA transcript during differentiation to neuronal cells has been developed in P19 embryonal carcinoma (EC) cells. The combined data suggest that 5' exons in the Mgat-1 gene are differentially utilized by tissue-specific promoters and that transcription factor(s) which specify production of the approximately 3.3 kb Mgat-1 mRNA are induced by retinoic acid treatment of P19 EC cells. PMID- 7881186 TI - Techniques for the application of the analytical solution to the multicylinder somatic shunt cable model for passive neurones. AB - The general solution for the voltage response to a generic impulse current input in a multicylinder somatic shunt cable model for passive neurones has been developed in [1]. In this paper we consider the application of the multicylinder solution to examples previously considered by other authors for the single cylinder case: long and short current input and synaptic input modeled by an alpha-function and a multi-exponential function. Simple expansions appropriate for small and large times are found and efficient means of obtaining these expansions are clearly demonstrated. The dependence of the small and large time solutions upon the dimensionless parameters appearing in the conservation of current condition at the soma is investigated. Relevant limits of these dimensionless parameters which further simplify the small and large time solutions are related back to equivalent dimensional problems of interest to the practitioner. The well-posedness of the dimensionless inverse problem is investigated and a method proposed for the solution of the dimensional inverse problem for the somatic shunt. PMID- 7881187 TI - Analysis of failure time in clonally propagated plant populations. AB - A problem originating in forest tree breeding concerns the number of clones needed in clonally propagated plantings to manage risk of failure due to an unforeseen catastrophic event. In this paper, we present a model for and analysis of time to failure for clonally propagated populations, assuming that in each year there is a chance for attack by an insect or pathogen. We develop the probability distribution of the number of years until population failure, T. A surprising finding is that in some circumstances increasing the number of clones can increase, rather than decrease, the chance of population failure. This suggests that laws, such as those current in the European Community, mandating minimum numbers of clones to be used in reforestation, may not achieve their intended effects, and that further investigation is needed to clarify the situation. PMID- 7881188 TI - Stochastic compartmental models with Prendville growth mechanisms. AB - We consider a stochastic compartmental model in which cells reproduce in accordance with a regulated birth and death process. We find expressions for the mean vector and covariance matrix for the number of cells in these compartments. We obtain the asymptotic behavior of the mean vector in the general case and explicit expressions for two compartmental and mammillary systems. PMID- 7881189 TI - Structural identifiability and indistinguishability of certain two-compartment models incorporating nonlinear efflux from the peripheral compartment. AB - A two-compartment model is considered where both compartments are observed and where the transfer efflux from the peripheral compartment may take three different nonlinear forms. The structural identifiability of the set of unknown parameters of each possible model is examined using the similarity transformation approach. Using the recent extension of this approach the indistinguishability of pairs of the postulated systems is also considered. PMID- 7881190 TI - A universal model of single-unit sensory receptor action. AB - We present a model governing the operation of all "isolated" sensory receptors with their primary afferent neurons. The input to the system is the intensity of a sensory signal, be it chemical, optical etc., and the output is the rate of neural impulse transmission in the afferent neuron. The model is based on the premise that information is conserved when transmitted by an efficient sensory channel. Earlier studies on this informational or entropic model of receptor function were constrained to the cases where the sensory stimulus assumed the form of an infinite step function. The theory was quite successful in treating mathematically all responses to such elementary sensory stimuli--both neural, and by extension, psychophysical. For example, the theory unified the logarithmic and power laws of sensation. However, the earlier model was incapable of predicting responses to time-varying stimuli. The generalized model, which we present here, accounts for both steady and time-varying signals. We show that more intense stimuli are remembered by sensory receptors for longer periods of time than are less intense stimuli. PMID- 7881191 TI - Modeling defective interfering virus therapy for AIDS: conditions for DIV survival. AB - The administration of a genetically engineered defective interfering virus (DIV) that interferes with HIV-1 replication has been proposed as a therapy for HIV-1 infection and AIDS. The proposed interfering virus, which is designed to superinfect HIV-1 infected cells, carries ribozymes that cleave conserved regions in HIV-1 RNA that code for the viral envelope protein. Thus DIV infection of HIV 1 infected cells should reduce or eliminate viral production by these cells. The success of this therapeutic strategy will depend both on the intercellular interaction of DIV and HIV-1, and on the overall dynamics of virus and T cells in the body. To study these dynamical issues, we have constructed a mathematical model of the interaction of HIV-1, DIV, and CD4+ cells in vivo. The results of both mathematical analysis and numerical simulation indicate that survival of the engineered DIV purely on a peripheral blood HIV-1 infection is unlikely. However, analytical results indicate that DIV might well survive on HIV-1 infected CD4+ cells in lymphoid organs such as lymph nodes and spleen, or on other HIV-1 infected cells in these organs. PMID- 7881192 TI - Global stability for the SEIR model in epidemiology. AB - The SEIR model with nonlinear incidence rates in epidemiology is studied. Global stability of the endemic equilibrium is proved using a general criterion for the orbital stability of periodic orbits associated with higher-dimensional nonlinear autonomous systems as well as the theory of competitive systems of differential equations. PMID- 7881193 TI - Mathematical model of erythrocytes as point-like sources. AB - A new approach to investigate the effect of pericapillary gradients, caused by the particulate nature of blood, on oxygen partial pressure (pO2) in tissue is presented. The blood erythrocytes are modeled as point-like sources, which makes the system independent of the geometry of the erythrocytes. This model is semi analytical and is developed to estimate the pO2 far from the erythrocytes. It does so through calculation of the extraction pressure, which accounts for the capillary oxygen drop as compared to homogeneous blood. It is particularly useful to estimate pO2 in regions where the oxygen concentration is low. Simulations have been performed for a cylindrical tissue geometry and parameters are chosen for rat heart muscle. In accordance with the literature, for a fixed total oxygen supply low hematocrit values result in a lower pO2 at the border of the tissue cylinder than high values do. Also a decrease in hematocrit results in higher values for the extraction pressure. Finally, it was found that the effect of the particulate nature of blood is most distinct at low hematocrit values. PMID- 7881194 TI - Drug kinetics and drug resistance in optimal chemotherapy. AB - A system of differential equations for the control of tumor cells growth in a cycle nonspecific chemotherapy is presented. First-order drug kinetics and drug resistance are taken into account in a class of optimal control problems. The results show that the strategy corresponding to the maximum rate of drug injection is optimal for the Malthusian model of cell growth (which is a relatively good model for the initial phase of tumor growth). For more general models of cell growth, this strategy proved to be suboptimal under certain conditions. PMID- 7881195 TI - Chemotherapeutic treatments involving drug resistance and level of normal cells as a criterion of toxicity. AB - A system of differential equations for the control of tumor cells growth in a cycle nonspecific chemotherapy is presented. Drug resistance and toxicity conveyed through the level of normal cells are taken into account in a class of optimal control problems. Alternative treatments for the exponential tumor growth are set forth for cases where optimal treatments are not available. PMID- 7881196 TI - The global bifurcation structure of the BVP neuronal model driven by periodic pulse trains. AB - The response characteristics of the BVP (Bonhoeffer-van der Pol or FitzHugh Nagumo) neuronal model to periodic pulse trains were investigated. The global bifurcation structure of model relative to stimulus intensity and period were analyzed using a one-dimensional mapping called the phase transition curve (PTC) extended by Maginu. The PTC clarified how periodic and chaotic responses bifurcate and revealed in particular several examples of chaotic responses bifurcating through period-doubling bifurcations, as well as the coexistences at the same parameter values, of two different periodic orbits, or of a chaotic and a periodic responses. PMID- 7881197 TI - Are abnormalities of human organizational genes responsible for causing birth defects? PMID- 7881198 TI - The effects of benzodiazepine use during pregnancy and lactation. AB - Although there are a number of studies and individual case reports concerning the use of benzodiazepines in human pregnancy, the data concerning teratogenicity and effects on postnatal development and behaviour are inconsistent. There is evidence from studies in the 1970s that first trimester exposure to benzodiazepines in utero has resulted in the birth of some infants with facial clefts, cardiac malformations, and other multiple malformations, but no syndrome of defects. Diazepam and chlordiazepoxide are amongst the drugs most frequently implicated in the earlier studies. However, data from later studies provide no clear evidence of significant increase in either the overall incidence of malformations or of any particular type of defect. Many of the women included in these studies has psychiatric illnesses, epilepsy, or diabetes all of which have an intrinsic risk in pregnancy, and some were on multidrug therapy. Medical obstetric histories and family history of malformations were not always presented in the publications, which makes assessment of risk associated with benzodiazepine use per se difficult. Nevertheless, in most of the studies involving first trimester use of benzodiazepines, the majority of infants were normal at birth and had normal postnatal development. Late third trimester use and exposure during labour seems to be associated with much greater risks to the fetus/neonate. Some, but by no means all infants exposed at this time, exhibit either the floppy infant syndrome, or marked neonatal withdrawal symptoms. Symptoms vary from mild sedation, hypotonia, and reluctance to suck, to apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. These symptoms have been reported to persist for periods from hours to months after birth. This correlates well with the pharmacokinetic and placental transfer of the benzodiazepines and their disposition in the neonate. However, there has been no significant increase in the incidence of neonatal jaundice and kernicterus in term infants. The prolonged use of benzodiazepines throughout pregnancy raised the concern that there may be altered transmitter synthesis and function, leading to neurobehavioural problems in the children. In approximately 550 children who were followed up for various times up to four years of age, there is no increase in either the malformation rate or adverse effects on neurobehavioural development and IQ. Although some of the data indicate that a small number of children were slower to develop during the first year or so, they did exhibit catch up growth and most had developed normally by four years of age. Where developmental deficits persisted, it was not possible to prove a cause-effect relationship with benzodiazepine exposure. These children were often from families where there was maternal illness requiring prolonged drug therapy or where there were social problems. It is important to consider poor environmental and social factors when assessing the possible prenatal influence of the benzodiazepines on the postnatal health and development of the child. There is evidence that clonazepam, clorazepate, diazepam, lorazepam, midazolam, nitrazepam, and oxazepam are excreted into breast milk. The published data indicate that the levels detected in breast milk are low; therefore, the suckling infant is unlikely to ingest significant amounts of the drug in this way. Problems may arise if the infant is premature or has been exposed to high concentrations of drug either during pregnancy or at delivery. PMID- 7881199 TI - Mechanisms of the stimulation of rat uterine peroxidase activity by methoxychlor. AB - Methoxychlor (MXC) has adverse effects on fertility and rat uteri via its active metabolite HPTE (2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane). Uterine peroxidase, a marker of estrogen action, was used to probe potential mechanisms of MXC's adverse effects. Specifically, our objective was to compare the regulation of the effects of estrogen and MXC on uterine peroxidase. Immature female rats were treated with MXC (250 mg/kg; gavage) 24 h prior to the measurement of uterine peroxidase activity, with or without concurrent treatment with actinomycin D, cycloheximide, progesterone, or tamoxifen. MXC alone produced an increase in peroxidase activity. The prior and/or concurrent treatment with the compounds listed blocked the MXC-induced stimulation of peroxidase. These data show similarities between the mechanisms of estrogen MXC action. Both estrogen and MXC act to stimulate uterine peroxidase activity via increased RNA and protein synthesis and this stimulation can be blocked by progesterone and tamoxifen. PMID- 7881200 TI - Reproductive toxicity of Aroclor-1254: effects on oocyte, spermatozoa, in vitro fertilization, and embryo development in the mouse. AB - Polychlorinated biphenyls (PCBs) have been reported to adversely affect reproduction in laboratory and wild animals. The present study was undertaken to determine the toxic potential of Aroclor-1254 (A-1254) on in vitro fertilizing ability of oocytes and epididymal sperm and on preimplantation embryo development in the mouse. A-1254 was added to the IVF medium at concentrations of 0.01, 0.1, 1.0, and 10.0 micrograms/mL. Cumulus masses containing the oocytes were obtained from superovulated B6D2F1 mice and were placed in the culture medium containing A 1254 to which epididymal sperm, capacitated in a medium without A-1254, were added. The IVF rate was assessed 20 to 24 h after insemination. A-1254 significantly reduced the mean percent ova fertilized even at 0.1 microgram/mL. Incubation of the cumulus masses in various concentrations of A-1254 for 6 h, followed by insemination with sperm capacitated in the presence of A-1254, also significantly reduced the IVF rate. Capacitation of sperm in A-1254-containing medium, followed by coculture with untreated oocytes, failed to affect the IVF rate. No significant effect on sperm motility was observed following exposure to 1 and 10 micrograms/mL of A-1254. Estradiol-17 beta also reduced the IVF rate, however, the effect of A-1254 was more severe compared to the estradiol treatment. Furthermore, addition of A-1254 to the embryo culture medium was associated with a significant decrease in embryo growth at 48 h and 96 h. These results demonstrate adverse effects of A-1254 on oocytes, IVF, and embryonic development in the mouse. PMID- 7881201 TI - Acute cadmium exposure and ovarian steroidogenesis in cycling and pregnant rats. AB - The purpose of this study was to evaluate the effect(s) of acute in vivo cadmium (Cd) exposure on steroidogenesis in rat ovaries during different reproductive states. Sprague-Dawley rats were injected subcutaneously on the day of diestrus, or on day 7 or 16 of gestation with a single dose of 0, 3, or 5 mg Cd/kg bw, and evaluated 24 h later. Serum progesterone and estradiol concentrations were determined. Whole-ovary culture was used to evaluate Cd effects on the production of progesterone, testosterone, and estradiol. Liver, kidney, spleen, ovary, placenta, and blood were analyzed for Cd and iron (Fe) concentrations. No general toxic effects, no disruption of estrous cyclicity, and no change in fetal viability were seen. Histologic evaluation revealed moderate Cd-related thecal congestion in ovaries of pregnant rats. The highest Cd concentrations, except for liver, were found in the fetal portion of the placenta. Interestingly, Cd-related decreases in Fe concentration were found in several tissues from rats in proestrus and on gestation day 8, and in fetal placenta from rats on gestation day 17. Cadmium appears to interfere with normal steroidogenesis at a number of sites in the biosynthetic pathway with serum estradiol concentration and ovarian estradiol production the most affected. Acute Cd effects on steroidogenesis are most severe in rats evaluated in proestrus or in early pregnancy, while in late pregnancy steroidogenesis is relatively unaffected. PMID- 7881202 TI - Destruction of preantral follicles in adult rats by 4-vinyl-1-cyclohexene diepoxide. AB - 4-vinyl-1-cyclohexene diepoxide (VCD) is known to destroy oocytes in ovaries of immature rats. Since ovaries functionally differ between immature and adult animals, we examined the effect of VCD on oocytes in adult rats. Adult (58 days) and immature (28 days) rats were injected daily (30 days) with vehicle or VCD. Each group contained 10 rats. During this time, cyclicity was determined daily by vaginal cytology. Animals were terminated on day 31 and tissues were collected. Oocytes were counted; livers, spleens, and uteri were weighed. VCD reduced the number of regular estrous cycles/30 days in adults, but not immature rats (n = 20, P < 0.05). VCD reduced the number of oocytes in adult and immature rats (n = 20, P < 0.05). Liver, spleen, or ovarian weights were not affected by VCD in either group. VCD reduced uterine weight in adult (n = 20, P < 0.05) but not in immature rats. These results demonstrate that VCD decreases uterine weight in adult rats and as with immature rats, selectively destroys oocytes in ovaries of adults. PMID- 7881203 TI - Growth variability in avian embryos as a source of experimental error. AB - To reduce variability in an embryonic population to be used in experiments with electromagnetic fields, 820 Japanese quail eggs (41 experiments, 20 eggs per experiment) were incubated to analyze different possible inputs of experimental variance. Eggs came from a randombred progenitor population obtained from a poultry farm and selectively maintained. The results show that growth variability is significantly higher in some progenies, which show bimodal distributions; this is evidence of the existence of a dichotomous population with different growth velocities within these populations. This phenomenon seems to be the result of growth factors inherited from the progenitors and not of environmental factors. A genetic selection of the progenitors used in the experimental lines dealing with growth variability in birds seems necessary to reduce any possible erroneous interpretation of the experimental results. PMID- 7881204 TI - Automated analysis of toxicant-induced changes in rat sperm head morphometry. AB - An automated sperm morphometry analysis (ASMA) instrument was developed to obtain measurements of toxicant-induced changes in rat sperm head morphometry. 1,3 dinitrobenzene (1,3-DNB), a testicular toxicant known to affect sperm parameters, was used. Twelve-week-old Sprague-Dawley rats were allocated to a control (C) and to two 1,3-DNB treatment groups (T1 = 15 mg/kg; T2 = 25 mg/kg). 1,3-DNB was administered as a single dose by gavage, and animals were sacrificed 22 days after exposure. Sperm were collected, and morphology smears were made by a standard method. One hundred sperm heads were digitized on each slide, and 8 metric measurements were automatically reported. All measurements tended to decrease in a dose-dependent manner with increasing doses of 1,3-DNB. All values for total width (Wa) and interior width (W(e)) were significantly different from one another. Wa/L was significantly larger in the control than in T1 or T2, and symmetry (S = Wb/Wa) was significantly smaller in the control than in T1 or T2. Multivariate cluster analysis revealed three subpopulations that were also visually distinct. Subpopulation no. 1 was normal, based on published descriptions of normal rat sperm; subpopulation no. 2 was abnormal with a flattened curvature and a normal length; subpopulation no. 3 was abnormal with a foreshortened length and a flattened curvature. T1 and T2 contained significantly more sperm from subpopulation no. 2 and no. 3 than C (T1 = 22% and T2 = 34% vs. C = 8% by cluster analysis). C had 93% normal sperm, while the treatments had 78% and 66%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881205 TI - Population and community effects of sediment contamination from residential urban runoff on benthic macroinvertebrate biomass and abundance. PMID- 7881206 TI - Effect of pH and time on the acute toxicity of copper sulfate to the ciliate protozoan Tetrahymena thermophila. PMID- 7881207 TI - Environmental factors affecting mercury methylation in estuarine sediments. PMID- 7881208 TI - Leaching from stone crab traps dipped in fungitrol: diesel fuel preservative. PMID- 7881210 TI - Impact of chemigation on selected non-target aquatic organisms in cranberry bogs of British Columbia. PMID- 7881209 TI - PCB and metal concentrations in American lobsters from the Acushnet River Estuary and Long Island Sound. PMID- 7881211 TI - Avoidance behavior test as an alternative to acute toxicity test. PMID- 7881212 TI - Comparison of metal concentrations in the fore and hindguts of the crayfish Cambarus bartoni and Orconectes virilis and implications regarding metal absorption efficiencies. PMID- 7881213 TI - Metolachlor and 2,4-dichlorophenoxyacetic acid sensitivity of Salvinia natans. PMID- 7881214 TI - Reduction by fluoranthene of copper and lead accumulation in Triticum aestivum L. PMID- 7881215 TI - Paraoxon inhibits fertilization of mouse gametes in vitro. PMID- 7881216 TI - Effects of exposure to an organophosphate on the seed-handling efficiency of the house sparrow. PMID- 7881217 TI - Residual content of hexachlorobenzene in Spanish cheeses. PMID- 7881218 TI - Dissipation of pyrazophos residues in greenhouse tomatoes. PMID- 7881219 TI - Characterization and aliphatic aldehyde content of particulates in Chinese incense smoke. PMID- 7881220 TI - Analyses of liquid diazinon formulations and breakdown products: an Australia wide survey. PMID- 7881221 TI - Nonextractable (bound) residues of cypermethrin in soils. PMID- 7881222 TI - Simple technique for estimation of biofilm accumulation. PMID- 7881223 TI - Fluorescent dye, pesticide and surfactant penetration tested in simulated spill. Part II. Nonwoven fabrics as barriers. PMID- 7881225 TI - Developmental toxicity evaluation of zinc dimethyldithiocarbamate (Ziram) in rats. PMID- 7881224 TI - Use of the anaphase-telophase test to detect aneugenic compounds: effects of propionaldehyde and cadmium chloride. PMID- 7881226 TI - Abnormal pinna type and hearing loss correlations in Down's syndrome. AB - Significant hearing loss and external pinna malformations are two of the most common defects evident in Down's syndrome. The external and middle ears are linked embryologically, both arising from the first and second branchial arches. Evidence indicates that the majority of hearing loss in Down's syndrome is conductive in nature, originating from malformations of the middle ear ossicles and/or the eustachian tube. Recent studies also have indicated that hearing loss is a contributing factor to the IQ and learning deficits that afflict most individuals with Down's syndrome. Therefore, an early, external diagnostic feature for predicting conductive hearing loss would be desirable. In the current study, people with Down's syndrome, people with non-Down's mental retardation and control subjects were examined in a clinical environment for the presence of hearing loss and pinna defects. It was found that 90% of the Down's syndrome population had significant hearing loss, compared to slightly more than 50% in the non-Down's group and no hearing loss in the controls. Also, the majority of hearing loss among individuals with Down's syndrome was conductive, while all hearing loss in the non-Down's group was sensorineural. The Down's syndrome population exhibited nearly 3.5 pinna defects per ear, with malformations of the helix being very evident. The non-Down's population exhibited 2.5 pinna defects per ear, with concha defects being the most common. PMID- 7881227 TI - Comparison of community and institutional prescription of antiepileptic drugs for individuals with learning disabilities. AB - The use of antiepileptic agents for individuals with learning disabilities (mental handicap) resident both within National Health Service facilities and the community was surveyed in the UK. There was no difference in rates of polypharmacy, but there were significant differences in choice of antiepileptic agent. In particular, individuals resident in the community were more likely to be in receipt of phenytoin, primidone and phenobarbitone, which are particularly recognized as producing adverse effects on cognition and behaviour. PMID- 7881229 TI - A study of the prescribing for people with learning disabilities living in the community and in National Health Service care. AB - The prescribing of medicines for people with learning disabilities living in Leicestershire, England, was surveyed. Prescribing in both National Health Service (NHS) and non-NHS settings was compared. PMID- 7881228 TI - A move from hospital to community-based homes for people with learning disabilities: activities outside the home. AB - Eighteen people with learning disabilities who moved from hospital to community based homes were compared with a matched group of 18 who did not. A week-long time budget diary was used to record each occasion that the person left their home, the people accompanying them on each trip, their mode of transport and their destination. The diary was completed before they left the hospital and was repeated at least 1 year later. There was a strong correlation between the number of trips made from hospital wards at baseline and the number made at follow-up in both groups. Moving from the hospital had no significant effect on the number of trips made, but it did change their nature. Movers made more trips to unsegregated facilities; they made fewer trips alone and more in groups which included both staff and residents. PMID- 7881230 TI - Towards the development of a multi-axial classification of people with learning difficulties. AB - The complexity of need experienced by people with learning disabilities might best be described by a multi-axial classification. The data routinely collected for a register of people with learning disabilities were analysed to see whether factors that might discriminate between individuals could be identified. Three factors were identified. The factor scores were used in a cluster analysis. A ten cluster model formed from these factors made empirical sense. The present investigation indicates that a multi-axial classification is feasible and may be useful. However, the results cannot be applied beyond the data set used for its development at the present time. Ultimately, it will be necessary to collect additional information in order to calibrate the factor scores. PMID- 7881231 TI - Automatic processing in mildly retarded and nonretarded persons. AB - Mildly retarded adults, equal mental age nonretarded children, high mental age nonretarded children, equal chronological age nonretarded adults and young nonretarded adults were required to perform a priming task (letters/digits) in which some primes were masked (visual noise mask) at just below detection levels to assess automatic processing. The critical (just below detection level) prime mask stimulus onset asynchronies (SOAs) were established individually for each subject using the method of limits and reassessed after the experimental trials. The mean critical SOA for each of the five groups was comparable and the critical SOAs remained stable across the 120 experimental trials for all groups. The nonretarded adult subjects demonstrated semantic, categorical and orthographic priming. The mildly retarded, the equal-MA and the high-MA groups failed to demonstrate priming, and in fact, demonstrated superior performance for prime target conditions which should have been poorest. This finding was discussed in terms of the level of specificity engendered in the priming task. Under the mask procedure, the nonretarded adult groups demonstrated semantic (letter) priming and orthographic priming, suggesting that letters (not digits) function as an analog to words which were employed in earlier masked prime lexical decision tasks. The mentally retarded, the equal-MA and the high-MA groups again failed to demonstrate priming under the mask procedure. PMID- 7881232 TI - Is there an inverse relationship between Down's syndrome and bipolar affective disorder? Literature review and genetic implications. AB - Several authors have suggested the existence of an inverse relationship between bipolar affective disorder and Down's syndrome (DS). The present authors have examined this hypothesis by a critical review of the literature. The present findings are consistent with a reduced rate of bipolar disorder in subjects with DS when compared with non-DS mentally retarded adults and with the general population. Thus, possession of an extra copy of chromosome 21 may confer protection against bipolar disorder. This could be the result of non-specific mechanisms or the action of a disease-modifying gene. However, the most interesting possibility is that either dominant or recessive alleles act at a major susceptibility locus for bipolar disorder on chromosome 21. Testable predictions result from the major susceptibility locus models. In order to investigate these hypotheses further, the present authors suggest the following: (1) further studies of the prevalence of bipolar disorder in DS; and (2) the reporting of all cases of bipolar disorder in trisomy 21 with details of the meiotic origin of the non-disjunction and details about affective disorder in relatives of the proband. PMID- 7881233 TI - Tentative classification of neuropsychiatric disturbances in Prader-Willi syndrome. AB - Prader-Willi syndrome presents behavioural characteristics at the temperamental level which can be described as oppositional, explosive and at times antisocial. These traits may fluctuate and be driven by unknown biological anxiety symptoms are also frequent. Delusional psychotic thinking is manifest in some cases, but may be latent in several such patients. A third set of manifestations is a 'refusal-lethargy' syndrome of akinesis, refusal of food and drink, and soiling, which seems to be triggered by environmental circumstances but resembles the hypersomnic, lethargic depressions. These three sets of phenomena are documented through the clinical observation of nine cases and may be useful in the study of the genotype-phenotype relationship in this and other syndromes, particularly those in which similar manifestations are observed and cyclic changes are seen. The use of drugs in this syndrome can also become more rational if this classification is used to identify clearer targets for treatment. The possibility that most manifestations of the syndrome may be an expression of a hyposerotonergic defect is suggested. PMID- 7881234 TI - Effect of intrathecal saline injection and Valsalva maneuver on cerebral perfusion pressure during transsphenoidal surgery for pituitary macroadenoma. AB - Cerebrospinal fluid pressure (CSFP) was monitored through a lumbar intrathecal catheter in 32 patients undergoing transsphenoidal excision of pituitary macroadenomas. In the first 20 patients, standardized intermittent Valsalva maneuvers were followed by intrathecal saline injections in 2.5-ml increments. Their effects on CSFP, mean arterial pressure (MAP), and therefore, cerebral perfusion pressure (CPP) were compared. The increase in CSFP produced by one Valsalva maneuver (4 +/- 2 mm Hg) was similar to that produced by a single increment of intrathecal saline (4 +/- 2 mm Hg), but the effect of saline was more sustained. With Valsalva maneuvers, the maximum CSFP produced was 13 +/- 4 mm Hg, and the CPP decreased to 50 +/- 14 mm Hg, whereas with saline, the maximum CSFP was 25 +/- 7 mm Hg, and the CPP decreased to 59 +/- 13 mm Hg. Because the increase in CSFP was greater and better sustained with intrathecal saline, Valsalva maneuvers were omitted in the next 12 patients. Peroperative data, including surgical conditions, and post-operative morbidity, with special reference to low-pressure headache and meningeal infection, were analyzed in all 32 patients. Operative conditions produced with intrathecal saline were judged excellent or good in 75% of patients. However, because this technique can decrease the CPP excessively, we recommend that it be used only with continuous CSFP monitoring. PMID- 7881235 TI - Association between electrocardiographic abnormalities and intracranial blood in patients following acute subarachnoid hemorrhage. AB - The etiological factors that influence the development of electrocardiographic (ECG) abnormalities following a subarachnoid hemorrhage are not fully understood. The purpose of this study was to assess if there was an association between ECG abnormalities and the amount of intracranial blood seen on computerized tomographic (CT) scanning following an acute bleed in patients with a cerebral aneurysm. The charts of 70 patients who had had a preoperative CT scan and a preoperative ECG within 96 h of bleed were reviewed. The neurological status of the patients was graded according to the Botterell classification and the amount of blood seen on the CT scan was graded by the Fisher classification. Thirty patients had an abnormal ECG. Seventy percent of these abnormalities involved the T wave or the ST segment. The incidence of ECG abnormalities was statistically greater for patients who had an increased amount of intracranial blood or an intracerebral clot, as seen on CT scan. All patients had treatment (surgical n = 69, embolization n = 1) of the aneurysm. Neither the amount of blood seen on CT scan nor the incidence of ECG abnormalities was useful in predicting patient outcome. In conclusion, an increased quantity of intracranial blood was associated with an increased incidence of ECG abnormalities. PMID- 7881237 TI - Life-threatening hemorrhagic diathesis due to disseminated intravascular coagulation during elective brain tumor surgery. AB - Disseminated intravascular coagulation (DIC) is an extremely rare complication during elective brain tumor surgery. We report the case of a life-threatening intraoperative hemorrhagic diathesis due to a fulminating DIC during the removal of a grade III parietooccipital astrocytoma in a patient with a history of three pulmonary embolisms. Intraoperatively, the patient required 13 U of blood, 9 U of fresh-frozen plasma, and 5.45 L of colloids and crystalloids (total volume infused during the procedure: 12.5 L). Bleeding persisted for 24 h and required further blood component therapy. Laboratory data support the diagnosis of DIC: decreased fibrinogen and platelet count, prolonged thrombin and prothrombin times, and the presence of fibrin monomers. With aggressive and swift treatment of the DIC, the patient survived with transient neurological worsening. PMID- 7881236 TI - Brain edema and neurologic status with rapid infusion of 0.9% saline or 5% dextrose after head trauma. AB - We previously reported that intravenous (i.v.) administration of large volumes (0.2 ml/g) of either an isotonic dextrose-free solution or 5% dextrose solution given over 18 h after closed head trauma (CHT) in rats did not significantly affect neurological severity score or brain tissue specific gravity. However, it is possible that with more rapid administration, isotonic or 5% dextrose i.v. solutions may alter neurological outcome after CHT. Our study examined whether neurological severity score, brain tissue specific gravity and water content, and blood composition were significantly altered when 0.25 ml/g of either 0.9% saline or 5% dextrose was given i.v. over 0.5 h (rather than over 18 h) after CHT. Eight four rats that survived ether anesthesia and CHT were randomly assigned to one of 11 experimental groups. Saline- and dextrose-treated rats were evaluated at 4 and 48 h after CHT and were compared to rats without CHT and to untreated rats at 4 and 48 h after CHT. There were no statistically significant differences in neurologic outcome and brain edema between the untreated and the saline-treated groups. However, 5% dextrose i.v. increased mortality (group 6 and 11, 50 and 0% survivors, respectively), decreased specific gravity in the noncontused hemisphere, and worsened neurologic outcome with and without CHT. Blood osmolality remained stable in comparison to the baseline value of 291.9 +/- 7.4 mOsm/kg (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881238 TI - Hypothermia in anesthesia and critical care. PMID- 7881239 TI - Deliberate mild hypothermia. AB - Core body temperature is normally rigidly regulated by effective thermoregulatory responses that are triggered by small deviations in core and skin temperature. All general anesthetics so far tested markedly impair thermoregulatory control, increasing the range of temperatures not triggering protective responses by approximately 20-fold. Inhibition of thermoregulatory control--and reemergence of protective responses--are major factors influencing intraoperative temperature. Mild hypothermia provides dramatic protection against cerebral ischemia and therefore is frequently indicated during neurosurgery. Hypothermia to core temperatures near 34 degrees C can usually be instituted passively so long as thermoregulatory vasoconstriction is inhibited by sufficient anesthesia or neurosurgery per se. When core temperature must be rapidly reduced, or reduced to values approaching 32 degrees C, active cooling will usually be needed. Forced air appears to be the most effective clinically practical cooling method. Mild hypothermia is also associated with serious complications including myocardial ischemia, impaired resistance to surgical wound infections, coagulopathies, and postoperative shivering. Consequently, patients deliberately made hypothermic during neurosurgery should subsequently be actively rewarmed. PMID- 7881240 TI - The biochemical basis of cerebral ischemic damage. PMID- 7881241 TI - Cerebral perfusion and hypothermia. PMID- 7881242 TI - Spontaneous ventilation is not a sensitive indicator of brain stem well-being. PMID- 7881243 TI - Spontaneous ventilation is a useful monitor of brain stem function during posterior fossa surgery. PMID- 7881244 TI - Low-dose sufentanil increases cerebrospinal fluid pressure in human volunteers. AB - Although sufentanil is frequently used in neuroanesthesia, the effect of the drug on intracranial pressure is still controversial. In our study, we used an invasive measurement technique to study the effects of 0.1 micrograms/kg-1 sufentanil on mean lumbar cerebrospinal fluid pressure (CSFP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP), central venous pressure (CVP), heart rate (HR), and end-tidal dioxide (ETCO2) in five human volunteers. After i.v. injection of sufentanil, mean lumbar CSFP increased from 6 mm Hg to 12 mm Hg (p < 0.05), and mean CPP decreased from 92 mm Hg to 78 mm Hg (p < 0.05), whereas MAP, CVP, HR, and ETCO2 remained stable. The results of this study clearly show that even a low dose of sufentanil transiently increases lumbar CSFP in volunteers with uncompromised intracranial compliance. PMID- 7881245 TI - Identifying family needs and stresses in the intensive care unit. AB - This article explores the effect that the intensive care unit has on patients' families and examines ways for nurses to identify and cope with family needs and stresses in the intensive care environment. PMID- 7881246 TI - Tamoxifen: scientific basis, use and nursing implications. AB - Tamoxifen is widely used as a treatment for breast cancer. This article considers the development, scientific basis and patient implications together with some current issues concerning the drug. The importance of using a scientific knowledge base to improve nursing practice is highlighted. PMID- 7881247 TI - Preserving children's nursing in a climate of genericism. PMID- 7881248 TI - Has the measles campaign been a wise use of resources? PMID- 7881249 TI - The value of children's nursing in the third millennium. AB - This article describes the origins of children's nursing and examines its role in a contemporary society approaching a new millennium. The controversial aspects of the generic nurse debate are explored and repudiated. PMID- 7881250 TI - Family-centred care within contemporary British paediatric nursing. AB - The concept of family-centred care is such a cherished tenet of paediatric nursing to be almost above critique. Yet a close examination of the place and meaning-in-practice of family-centred care is long overdue if the term is not to lapse into mere cliche or slogan. PMID- 7881251 TI - The development of the paediatric nurse specialist. AB - Paediatric nurse specialists have, in the past, pioneered new roles in response to clients' needs. As a result, clinical practice and the service provided to families have been innovatory. Future paediatric nurse specialists will continue to lead and develop clinical practice through audit and research. PMID- 7881252 TI - The growth of an NDU in a paediatric outpatient department. AB - The granting of nursing development unit (NDU) status to a paediatric clinical area indicates the desire to promote excellence in child care. This article describes the progress of the children's outpatient department at Southampton General Hospital since it was granted NDU status. PMID- 7881253 TI - Common problems in wound care: caring for the skin around wounds. AB - This article is the first in a monthly series which will address some of the common problems in wound care. Each article will discuss the nature of the problem and suggest appropriate management strategies. PMID- 7881255 TI - Research in nursing: developing a conceptual approach. AB - This article, the first in an ongoing series on research in nursing, argues that research, like nursing, is best understood by the practical application of ideas, but that action should not be taken until at least a basic research appreciation or literacy is attained. PMID- 7881254 TI - Issues for nursing in 1995. PMID- 7881256 TI - Making ends meet: hardship among student nurses. PMID- 7881257 TI - Mepitel. AB - This article describes a relatively new product on the market called Mepitel, a non-adherent dressing that is useful in the management of many wound types and skin conditions, ranging from leg ulcers and skin grafts to the treatment of epidermolysis bullosa. PMID- 7881258 TI - Law series: 1. Complaints. PMID- 7881259 TI - Nurse practitioners: do they enhance patient care? PMID- 7881260 TI - Primary nursing care of patients who have had a stroke. AB - This article describes the care of two patients who had had a stroke. It explores how their primary nurse and her colleagues learned to identify communication needs, and examines the development of strategies to help meet those needs. PMID- 7881261 TI - Some histopathological and clinical correlations in oral squamous cell carcinoma. AB - Oral squamous cell carcinoma (SCC) is an important health problem that causes high mortality and morbidity. Correlations between some clinical and histopathological parameters were studied in 37 oral SCC. Some interesting aspects in oral SCC arising from precancerous lesions were found such as smaller size and a lower TNM stage at the moment of diagnosis. Histological and clinical differences were also found between tumors invading deep tissues by little groups of dissociated malignant cells and those invading by big masses of malignant cells. The possible significance of the intensity of peritumoral eosinophilic infiltrate was also studied. PMID- 7881262 TI - [An analysis of the nasolabial angle]. AB - We analyzed the nasolabial angle and different factors that influence it in patients of 9.0 +/- 1.4 years of age. An average value of 115.30 +/- 10.8 was obtained. The inclination and the position of the upper incisive and the ANB angle constituted the osseous and dental factors with greatest repercussion on the nasolabial angle. Sex and age did not condition significant differences. The labial incompetence determined a more acute angle. PMID- 7881263 TI - Detection of human papillomavirus DNA sequences in leucocytes: a new approach to identify hematological markers of HPV infection in patients with oral SCC. AB - Squamous cell carcinoma of oral mucosa was shown to be associated with human papillomavirus (HPV) infection. The aim of this study was to find a hematological marker for HPV infection in patients with extensive HPV positive squamous cell carcinoma of the anterior oral cavity. In forty patients, referred to our clinic, suffering from histopathologically confirmed squamous cell carcinoma of the oral cavity with a tumor index T3/N2/M0 preoperative blood probes were taken. Human leucocytes were gained by FACS-lysis centrifugation. Paraffin-embedded sections of tumor tissue were deparaffinized and proteolytically digested to expose fixed target DNA. For detection of human papillomavirus, DNA sequences 6, 11, 16, 18, 31 and 33 a nonradioactive in situ hybridization technique was used (Biohid). For the first time we demonstrated HPV DNA sequences in leucocytes of patients with HPV positive oral SCC. Furthermore we found a correlation in type between HPV DNA sequences in tumor tissue and in leucocytes. This might lead to HPV as a hematological marker for follow up of patients with oral SCC and have consequences on therapy. PMID- 7881264 TI - Cyclosporine A, an alternative to the oral lichen planus erosive treatment. AB - We present a double-blind study in two groups afflicted with oral lichen planus erythematous of long evolution and resistant to other treatments. We tested on it a treatment with Cyclosporine A (CyA) which had been successfully used before by many dermatologists. In the group A we used mouthwashes with a 5 ml Cyclosporine A solution to a 10% in olive oil of 0.4 degrees of acidity for five minutes, three times a day for eight weeks. In the control group we used acetonide of triamcinolone 01% in aqueous solution. Patients in group A improved considerably in their symptomatology in a 90% against a 60% in group B. In group A we could appreciate a disappearance of the symptomatology after two weeks of treatment in 60% of patients against 30% in group B. CyA can be an alternative to the conventional treatments in the acute period of lichen planus although it can not be considered as a first option drug because of the high cost of the treatment. For long term, results are not so good and we consider that extensive studies are necessary. PMID- 7881265 TI - Anatomical considerations relevant to implant procedures in the mandible. AB - The authors review anatomical facts significant for preoperative planning of implant procedures in the mandible. This planning includes the precise evaluation of distinct anatomical factors, such as the position of the mandibular canal, the width of the mandibular cortical plates and the degree of involutive changes of the inferior dental artery. The mandibular canal is usually situated centrally in the mandibular corpus, slightly closer to the lingual cortex in its distal parts; towards the front, it approaches the vestibular cortical layer. Mesially from the mental foramen, a clearly defined incisive canal is present in only one third of the edentate mandibles. Mandibular corpus of the edentate mandibles consists of cancellous bone enclosed by a shell of compact cortical bone. Cortical layers demonstrate significant variations in width; nevertheless, the widths of lateral cortical layers, generally, enable safe placement of endosseous implants. Finally, in patient's preoperative assessment, involutive changes of the inferior dental artery should also be considered. During the involution of the mandibular alveolar process, it shows changes of direction and calibre, changes in arborization and, sometimes, complete occlusion of the main trunk. The degree of these involutive changes points out the mandibular vascular supply and the regenerative capacity of the tissues needed for the success of the implant procedure. PMID- 7881266 TI - Comparative study of heat release of various cement base materials during their setting. AB - An ideal cement base material in order to protect the pulpal tissue from several external irritations (microbial, mechanical, thermal, galvanic and osmotic irritations) must present the following requirements: to attach or bond to the residual dentin, to be biocompatible, to present suitable physicomechanical, antimicrobial and optical properties, to be color stable, easy to use and rapid to set. Thermal phenomena developed during the mixing and setting are a factor influencing the biocompatibility properties of these materials. Cement base materials are used under various types of filling materials (amalgams, composite resins, gold and porcelain inlays) and are placed in contact with the dentin that contains exposed dentinal tubules. The purpose of this study was to investigate the possible exothermic reaction of these materials and to measure the developing temperatures for a time period from their mixing up to the completion of their setting. We studied the following types of cement base materials: a) Zinc oxide eugenol cement, b) Zinc phosphate cement, c) Zinc polycarboxylate cement and d) Glass ionomer cement both light- and self-cured. From the obtained results we observed that ZOE cements developed the lowest temperatures ranging from 32.8 degrees C to 37 degrees C, while Zinc phosphate cements developed the highest temperatures ranging from 44.4 degrees C to 52 degrees C. The other two types of materials Zinc polycarboxylate and Glass ionomer cements developed biocompatible temperatures ranging from 38 degrees C to 40.8 degrees C, which usually do not cause deteriorations and harms to the pulp. We concluded that the ZOE cements presented the best thermal behaviour followed by Zinc polycarboxylate and Glass ionomer cements. Hence, these materials can be safely used without causing any pulpal response. PMID- 7881267 TI - [The measurement of the tooth-restoration material gap: the value of SEM]. AB - The purpose of this article was to describe a method of measuring the interface between cavity walls and restorative materials and to evaluate it by comparing the interface of amalgam, composite restorations and cavity walls. With the different restorative materials the interface could be measured. Its value was dependent of the type of restoration. This methodology is available for all restorative biomaterials. It could be of interest in clinical evaluation of restorative materials. PMID- 7881268 TI - Induction of interleukin-1 alpha production by Porphyromonas gingivalis in mononuclear blood cell cultures from periodontitis patients. AB - The capacity of mononuclear blood cells to produce interleukin-1 alpha (IL-1 alpha) after stimulation with Porphyromonas gingivalis in cell culture was studied. The results obtained with cells from periodontitis patients were compared with those from a control population. The concentration of IL-1 alpha in serum and saliva was also determined and compared with the concentration in mononuclear blood cell cultures. No significant relationship was found between the incidence of periodontitis or severity of the lesions and IL-1 alpha production in the presence of P. gingivalis. Nevertheless, 11 of 30 periodontitis patients, showed levels > 30 pg/ml of IL-1 alpha in mononuclear blood cell cultures stimulated by P. gingivalis, whereas only three healthy control showed these titers of IL-1 alpha. PMID- 7881269 TI - Three-dimensional structure of ectatomin from Ectatomma tuberculatum ant venom. AB - Two-dimensional 1H NMR techniques were used to determine the spatial structure of ectatomin, a toxin from the venom of the ant Ectatomma tuberculatum. Nearly complete proton resonance assignments for two chains of ectatomin (37 and 34 amino acid residues, respectively) were obtained using 2D TOCSY, DQF-COSY and NOESY experiments. The cross-peak volumes in NOESY spectra were used to define the local structure of the protein and generate accurate proton-proton distance constraints employing the MARDIGRAS program. Disulfide bonds were located by analyzing the global fold of ectatomin, calculated with the distance geometry program DIANA. These data, combined with data on the rate of exchange of amide protons with deuterium, were used to obtain a final set of 20 structures by DIANA. These structures were refined by unrestrained energy minimization using the CHARMm program. The resulting rms deviations over 20 structures (excluding the mobile N- and c-termini of each chain) are 0.75 A for backbone heavy atoms, and 1.25 A for all heavy atoms. The conformations of the two chains are similar. Each chain consists of two alpha-helices and a hinge region of four residues; this forms a hairpin structure which is stabilized by disulfide bridges. The hinge regions of the two chains are connected together by a third disulfide bridge. Thus, ectatomin forms a four-alpha-helical bundle structure. PMID- 7881270 TI - 'Random coil' 1H chemical shifts obtained as a function of temperature and trifluoroethanol concentration for the peptide series GGXGG. AB - Proton chemical shifts of a series of disordered linear peptides (H-Gly-Gly-X-Gly Gly-OH, with X being one of the 20 naturally occurring amino acids) have been obtained using 1D and 2D 1H NMR at pH 5.0 as a function of temperature and solvent composition. The use of 2D methods has allowed some ambiguities in side chain assignments in previous studies to be resolved. An additional benefit of the temperature data is that they can be used to obtain 'random coil' amide proton chemical shifts at any temperature between 278 and 318 K by interpolation. Changes of chemical shift as a function of trifluoroethanol concentration have also been determined at a variety of temperatures for a subset of peptides. Significant changes are found in backbone and side-chain amide proton chemical shifts in these 'random coil' peptides with increasing amounts of trifluoroethanol, suggesting that caution is required when interpreting chemical shift changes as a measure of helix formation in peptides in the presence of this solvent. Comparison of the proton chemical shifts obtained here for H-Gly-Gly-X Gly-Gly-OH with those for H-Gly-Gly-X-Ala-OH [Bundi, A. and Wuthrich, K., (1979) Biopolymers, 18, 285-297] and for Ac-Gly-Gly-X-Ala-Gly-Gly-NH2 [Wishart, D.S., Bigam, C.G., Holm, A., Hodges, R.S. and Sykes, B.D. (1995) J. Biomol. NMR, 5, 67 81] generally shows good agreement for CH protons, but reveals significant variability for NH protons. Amide proton chemical shifts appear to be highly sensitive to local sequence variations and probably also to solution conditions. Caution must therefore be exercised in any structural interpretation based on amide proton chemical shifts. PMID- 7881271 TI - (H)NCAHA and (H)CANNH experiments for the determination of the vicinal coupling constants related to the phi-torsion angle. AB - A set of three-dimensional triple-resonance experiments is described which provide 3J(HNHalpha), 3J(HNCO), 3J(HNCbeta) and 3J(HalphaCO) coupling constants. The pulse sequences generate E.COSY-like multiplet patterns and comprise a magnetization transfer from the amide proton to the alpha-proton or vice versa via the directly bound heteronuclei. For residues with the 1H(alph) spin resonating close to the H2O signal, a modified HNCA experiment can be employed to measure the vicinal 1H(N),1H(alpha) couplings. Ambiguities associated with the conversion of 3J(HNHalpha) values into phi-angle constraints for protein structure determination can be resolved with the knowledge of the heteronuclear 3J-couplings. In favourable cases, stereospecific assignments of glycine alpha protons can be obtained by employing the experiments described here in combination with NOE data. The methods are applied to flavodoxin from Desulfovibrio vulgaris. PMID- 7881272 TI - Selectively 13C-enriched DNA: dynamics of the C1'-H1' vector in d(CGCAAATTTGCG)2. AB - In order to examine the internal dynamic processes of the dodecamer d(CGCAAATTTGCG)2, the 13C-enriched oligonucleotide has been synthesized. The three central thymines were selectively 13C-labeled at the C1' position and their spin-lattice relaxation parameters R(CZ), R(CX,Y), R(HZ-->CZ), R(2HZCZ), R(2HZCX,Y) and R(HZC) were measured. Density functions were computed for two models of internal motions. Comparisons of the experimental data were made with spin-lattice relaxation rates rather than with the density functions, whose values were altered by accumulation of the uncertainties of each relaxation rate measurement. The spin-lattice relaxation rates were computed with respect to the motions of the sugar around the C1'-N1 bond. A two-state jump model between the anti- and syn-conformations with P(anti)/P(syn) = 91/9 or a restricted rotation model with delta chi = 28 degrees and an internal diffusion coefficient of 30 x 10(7) s-1 gave a good fit with the experimental data. Twist, tilt or roll base motions have little effect on 13C1' NMR relaxation. Simulation of spin-relaxation rates with the data obtained at several temperatures between 7 and 32 degrees C, where the dodecamer is double stranded, shows that the internal motion amplitude is independent of the temperature within this range, as expected for internal motion. Using the strong correlation which exists in a B-DNA structure between the chi and delta angle, we suggest that the change in the glycosidic angle value should be indicative of a sugar puckering between the C1'-exo and C2'-endo conformations. PMID- 7881273 TI - 1H, 13C and 15N random coil NMR chemical shifts of the common amino acids. I. Investigations of nearest-neighbor effects. AB - In this study we report on the 1H, 13C and 15N NMR chemical shifts for the random coil state and nearest-neighbor sequence effects measured from the protected linear hexapeptide Gly-Gly-X-Y-Gly-Gly (where X and Y are any of the 20 common amino acids). We present data for a set of 40 peptides (of the possible 400) including Gly-Gly-X-Ala-Gly-Gly and Gly-Gly-X-Pro-Gly-Gly, measured under identical aqueous conditions. Because all spectra were collected under identical experimental conditions, the data from the Gly-Gly-X-Ala-Gly-Gly series provide a complete and internally consistent set of 1H, 13C and 15N random coil chemical shifts for all 20 common amino acids. In addition, studies were also conducted into nearest-neighbor effects on the random coil shift arising from a variety of X and Y positional substitutions. Comparisons between the chemical shift measurements obtained from Gly-Gly-X-Ala-Gly-Gly and Gly-Gly-X-Pro-Gly-Gly reveal significant systematic shift differences arising from the presence of proline in the peptide sequence. Similarly, measurements of the chemical shift changes occurring for both alanine and proline (i.e., the residues in the Y position) are found to depend strongly on the type of amino acid substituted into the X position. These data lend support to the hypothesis that sequence effects play a significant role in determining peptide and protein chemical shifts. PMID- 7881274 TI - A novel method for selective isotope labeling of bacterially expressed proteins. AB - A novel method for isotope labeling in selected amino acids is presented for use with the T7 RNA polymerase system. The protocol is illustrated with the DNA binding domain from the E2 protein of bovine papillomavirus, BPV-1. On addition of rifampicin, protein expression occurs exclusively from the gene controlled by the T7 promoter. Since the bacteria are now dedicated to the production of E2 protein, labeling with specific amino acids is efficiently performed. For example, 10 mg/l of 15N-labeled phenylalanine is shown to be sufficient for incorporation of the label, without scrambling, and without the use of an auxotrophic strain. PMID- 7881275 TI - Concentration of copper, zinc, chromium, iron and nickel in the abdominal aorta of patients deceased with coronary heart disease. AB - The Cu, Zn, Cr, Fe, and Ni concentrations from the atherosclerotic plaques in the abdominal aorta obtained from 40 patients who died of coronary heart disease (CHD) were measured. In 32 of them the clinical and anatomical diagnosis was ischemic heart disease (IHD) and in 8 of them it was acute myocardial infarction (AMI). Concomitant determinations of the concentrations of the above trace elements were determined in 16 normal aortas from subjects who died in accidents or from causes other than atherosclerosis (C). The determinations were done by means of a Perkin-Elmer atomic absorption spectrophotometer, Model 300. The results are expressed in mg/kg of dried tissue. The Cu, Zn, and Cr concentrations were significantly lower (p < 0.01) in the atherosclerotic plaques of abdominal aorta of the deceased patients with IHD and AMI than in the control group. Iron had the tendency to rise but not significantly. The nickel level in the atherosclerotic plaques from abdominal aorta did not change significantly as compared to the controls. We attribute the low values of copper in the atherosclerotic aortic tissue in IHD and AMI to a shift of copper from aortic tissue into the blood. At present, there is no explanation for the low concentration of zinc and chromium in atherosclerotic aortic tissue. PMID- 7881276 TI - Sample preparation technique for iodine determination in urine and water samples. AB - A simple method for iodine determination in urine and water samples is presented. After digestion of the sample with chromic acid, the iodate produced was converted to iodide by the addition of a strong solution of sodium sulphite. The iodide was then precipitated as palladium iodide using a solution of palladium chloride. The precipitate was filtered through membrane filter paper, air-dried and analyzed using the Energy Dispersive X-Ray Fluorescence (EDXRF) method. PMID- 7881278 TI - Review of publications. PMID- 7881277 TI - Selenium and lipid parameters in plasma of Portuguese subjects. AB - To obtain further insight into the role of selenium in the development of atherosclerosis, plasma selenium and lipid parameters were determined in 126 Portuguese subjects living in the region of Lisbon, 60 women and 66 men, 20-60 years old, divided up in to three groups according to their plasma lipid profile: Group I consisted of normolipidemic subjects having plasma triglycerides and total cholesterol < 200mg/dL; Group II was composed of hypercholesteremic subjects with total cholesterol > 200mg/dL and plasma triglycerides < 200mg/dL; Group III was composed of hypercholesteremic and hypertriglyceremic subjects having total cholesterol and plasma triglycerides > 200mg/dL. Respective values for mean plasma selenium (+/- SD) in the groups were: 93 +/- 18 micrograms/L, 90 +/- 17 micrograms/L and 96 +/- 18 micrograms/L. A weak significant difference in plasma selenium between women and men was, however, observed in Group I (87 +/- 20 micrograms/L vs. 100 +/- 11 micrograms/L, p < 0.05). Regression analysis showed no significant relationship between plasma selenium and lipid parameters, except in the most hyperlipidemic women of Group III, where a weak correlation between plasma selenium and the HDL-cholesterol/total cholesterol ratio (r = 0.80, p < 0.05) was observed. The present study suggests that the relationship between selenium and HDL-cholesterol has to be further examined, taking into account nutritional, metabolic and genetic factors. PMID- 7881279 TI - The effect of zinc deficiency on erythrocyte membrane lipids of force-fed rats receiving a diet containing coconut oil or fish oil. AB - In the present study, the effect of zinc deficiency on erythrocyte membrane lipids of force-fed rats that received either a diet with coconut oil and safflower oil (86:14, w/w) or a diet with fish oil and safflower oil (91:9, w/w) was investigated. Zinc deficiency caused in the rats fed both types of dietary fat an increase in the amounts of total phospholipids and individual phospholipid classes in erythrocyte membranes. In the rats fed the coconut oil diet, zinc deficiency caused an increase in the proportion of docosahexaenoic acid (22:6) in phosphatidylcholine (PC), diacyl phosphatidylethanolamine (PE), phosphatidylserine (PS), and in total erythrocyte membrane fatty acids. In contrast, in the rats fed the fish oil diet, zinc deficiency caused an increase in the proportion of docosahexaenoic acid only in PC, but not in the other phospholipids. However, in these rats, changes in the ratio between eicosapentaenoic acid (20:5) and the n-3 fatty acids with 20 and 22 carbon atoms were observed in PC, diacyl PE and plasmalogen PE. The most pronounced changes in fatty acid composition due to zinc deficiency in the rats fed both types of fat occurred in PC. There was a relationship between the changes in the composition of plasma total fatty acids and the changes in fatty acid composition of erythrocyte membrane PC caused by zinc deficiency in the rats fed both types of dietary fat. The amount of cholesterol was similar in all treatment groups. However, zinc-deficient rats fed the coconut oil diet-but not those fed the fish oil diet-had an increased ratio between total phospholipids and cholesterol. Thus, the study shows that the effect of zinc deficiency on erythrocyte membrane lipids is to some degree similar for rats fed a coconut oil diet and rats fed a fish oil diet, and to some degree different. PMID- 7881280 TI - Influence of methionine and zinc supplementation during chelation of lead in rats. AB - The influence of methionine and Zn supplementation on the therapeutic efficacy of calcium disodium ethylenediamine tetraacetic acid (CaNa2 EDTA) and 2,3 dimercaptopropane 1-sulphonate (DMPS) in lead intoxication was investigated in rats. The combined treatment with CaNa2 EDTA and methionine +Zn or DMPS and methionine +Zn was more effective than the respective chelator alone in decreasing the blood and tissue burden of Pb and increasing urinary excretion of Pb, with the former combination being more effective than the later. However, simultaneous supplementation of the amino acid and essential trace element did not improve upon the efficacy of the chelator in reversing lead-induced biochemical alterations. PMID- 7881282 TI - Urinary element concentrations in kidney stone formers and normal controls: the week-end effect. AB - Early morning urines were collected on each of three days (Monday-Wednesday) from 19 male stone-formers and 20 healthy male controls. Concentrations of 10 elements were determined using inductively coupled plasma atomic emission spectroscopy, graphite furnace atomic absorption spectroscopy and particle induced x-ray emission spectrometry. Data were treated using multivariate statistical methods. The results showed that the concentrations of several elements in the control urines were significantly raised on Mondays and that controls and stone formers differed with respect to certain elements, also on Mondays. The observed elevations were termed the "weekend effect". It is suggested that while stone formers may regulate their diets throughout the entire week, normals may indulge in dietary excesses over the weekend. The weekend effect highlights the danger of placing too much emphasis on a single measurement of a urinary parameter and alerts investigators to take cognizance of the day on which urine collections are effected, especially when attempting to identify abnormal renal excretion patterns in stone-formers by comparison of their urinary variables with those of controls. PMID- 7881281 TI - Determination of total mercury in scalp hair of pregnant and nursing women resident in fishing villages in the Eighth Region of Chile. AB - Total mercury (Hg-T) content in scalp hair of 59 pregnant and nursing women-with normal to high fish and seafood consumption-resident in fishing villages distributed throughout the coastal zone of the Eighth Region of Chile, and of 7 pregnant and nursing women-with negligible or no fish and seafood consumption resident in a town located inland (Pinto) in the same region, was determined. Hair samples were collected, washed and stored according to IAEA recommendations, and were wet-digested in sealed Pyrex ampoules prior to the determination of Hg-T by gold amalgamation cold-vapour atomic absorption spectrometry. The absolute detection limit was estimated as 0.13 +/- 0.01 ng Hg-T (3 x sigma B1). Accuracy and precision were assessed with the aid of various biological and environmental certified and standard reference materials including human hair, and were satisfactory for ppm and sub-ppm Hg-T. Instrumental neutron activation analysis was used as a reference method for external quality control. The Hg-T content in hair of the study group (2.06 +/- 1.45(8) mg/Kg) was significantly higher than that of the control group (0.43 +/- 0.18(4) mg/kg) (p = 0.0001). These results were characterized according to geographical location, fish and seafood consumption, age and residence period in the fishing village. PMID- 7881283 TI - Sequential flow-injection determination of ionic and total calcium in saliva. AB - In this paper a flow injection manifold for the sequential determination of ionic and total calcium in a small (75 microL) sample of saliva is presented. This setup incorporates two detectors, a tubular potentiometric detector and an atomic absorption spectrophotometer, for determining the ionic and total calcium, respectively. Furthermore, the saliva samples can be injected directly into the manifold without any pre-treatment or loss of carbon dioxide. The results of the analyses of 20 saliva samples were in good agreement with those obtained by the two reference procedures, the direct potentiometry for ionic calcium and atomic absorption spectroscopy for total calcium. The paired Student's t-test showed that there were no statistical differences in the results obtained. The relative standard deviations of ten consecutive measurements of the same salive sample were approximately 3% for ionic calcium and 4% for total calcium. Effects of differences in coexisting ions, ionic strength, and pH between standard solutions and samples were negligible. PMID- 7881284 TI - Selenium concentration in serum of healthy Greek adults. AB - Serum selenium levels of 160 healthy Greeks were determined by Zeeman-effect background-corrected atomic absorption spectrometry. Mean value for 101 men (70.7 +/- 16.2 micrograms/L) tended to be higher, but not statistically significant, compared to the mean value for 59 women (64.9 +/- 14.7 micrograms/L). When the subjects were divided into various age groups there appeared to be some increase as a function of age. Compared to the extensive literature data on serum Se levels for various countries healthy Greeks proved to be at the lower concentration range. The scarce, but conflicting literature data on serum Se values for Greeks is discussed. PMID- 7881285 TI - Expression of dystrophin-associated glycoproteins and utrophin in carriers of Duchenne muscular dystrophy. AB - The expression of dystrophin, the dystrophin-associated proteins and utrophin has been studied immunocytochemically in three young, manifesting carriers of Duchenne muscular dystrophy, aged 3, 5 and 12 yrs, one adult manifesting carrier, aged 60 yrs, and one presumptive carrier with a raised serum creatine kinase, aged 24 yrs, the mother of the 5-yr-old manifesting carrier. The manifesting carriers had variable degrees of weakness; the presumptive carrier had no weakness. Morphological abnormalities were also variable and were most marked in the young manifesting carriers. The three young manifesting carriers and the presumptive carrier had a mosaic pattern of dystrophin-positive and dystrophin negative fibres. All the dystrophin-associated proteins were reduced in the dystrophin-deficient fibres, giving a similar mosaic pattern to dystrophin. Expression of dystrophin and the dystrophin-associated proteins was normal in the adult manifesting carrier. Utrophin was detected on the sarcolemma of fibres both with and without dystrophin and the dystrophin-associated proteins. Thus, dystrophin and utrophin are co-expressed in several fibres in carriers. The results emphasize the close association between dystrophin and the glycoprotein complex and their role in the pathogenesis of muscle damage. In addition, the presence of utrophin in fibres with greatly reduced glycoproteins suggests that very little of the glycoprotein complex may be required to anchor the amount of utrophin expressed at the sarcolemma in these particular cases. PMID- 7881286 TI - Carrier detection in DMD families with point mutations, using PCR-SSCP and direct sequencing. AB - Non-isotopic single-strand conformation polymorphism (SSCP) and direct sequencing was used for carrier diagnosis in four families of DMD/BMD patients with previously characterized point mutations, leading to the identification of eight carriers and four non-carriers. When the mutation caused a distinctly altered migration pattern of the single strands, in principle, the SSCP-technique allowed determination of carrier status in the extended family of the probands without direct sequencing. However, because SSCP measures a function of not only the mutation, but of the entire sequence of the PCR product, it can lead to false negative and/or false positive diagnoses due to intronic and exonic sequence heterogeneity in the family. As we discovered this pitfall in one of the reported families, we concluded that for carrier testing the SSCP approach must be performed in essential conjunction with an independent assessment of the mutation site by direct sequencing. PMID- 7881287 TI - Expression and subcellular localization of dystrophin in skeletal, cardiac and smooth muscles during the human development. AB - Dystrophin, the product of the DMD gene, is present in all muscle types in normal individuals. Its function has yet to be elucidated, but its absence or the presence of a truncated version of the protein is responsible for the appearance of Duchenne and Becker muscular dystrophies. Using monoclonal antibodies raised against distinct regions of the dystrophin protein, we have examined its expression and subcellular distribution during the human development in skeletal and smooth muscles. We show that both dystrophin expression and its association to the plasma membrane take place earlier in cardiac and smooth muscles (8 weeks of gestation) than in skeletal muscle. In skeletal muscle, dystrophin is first detected in the cytoplasm, and progressively localizes to the plasma membrane from 10 weeks onwards. Since we have obtained marked differences in staining when using antibodies against either a central region of the protein or the C-terminal part, we suggest that different fetal and adult dystrophin isoforms are expressed, probably differing in their C-terminal domain. These findings are discussed in the context of the pathology of Duchenne muscular dystrophy. PMID- 7881288 TI - Deletion of the dystrophin muscle promoter in feline muscular dystrophy. AB - We have characterized the mutation in a feline model of DMD that selectively eliminates expression of the muscle and Purkinje neuronal dystrophin isoforms. The cortical neuronal isoform was expressed at a detectable level in skeletal muscle in the absence of the muscle promoter and levels of PCR products representing cortical neuronal-type transcripts in dystrophic muscle were comparable to those of normal feline skeletal muscle. Although localized at the sarcolemma, cortical neuronal dystrophin apparently failed to protect skeletal muscle. Neuronal transcripts could not be amplified from feline heart, indicating that these promoters are not active in this tissue in the cat. PMID- 7881289 TI - The gene for X-linked myotubular myopathy is located in an 8 Mb region at the border of Xq27.3 and Xq28. AB - X-linked recessive myotubular myopathy (XLMTM) is a rare and severe neonatal neuromuscular disease characterized by muscle weakness, hypotonia, and respiratory problems. Here we report an extensive linkage analysis in two families with XLMTM. Using 18 markers in the Xq27-Xqter region we found a maximum two-point lod score of Z = 4.00 at theta = 0.00 for the marker II-10 (DXS466). Three recombinations were detected between markers and the disease locus. At the distal side of Xq27.3 a recombination was present in between RNI (DXS369) and VK23b (DXS297), another in between VK23b (DXS297) and II-10 (DXS466), and at the proximal side of Xq28 a recombination in between U6.2 (DXS304) and Cpx67 (DXS134). Combining the results of both families we conclude that XLMTM is located in the 8 Mb(11 cM) region between VK23b (DXS297) and Cpx67 (DXS134). PMID- 7881290 TI - Linkage analyses between dominant X-linked Charcot-Marie-Tooth disease, and 15 Xq11-Xq21 microsatellites in a new large family: three new markers are closely linked to the gene. AB - X-linked dominant inheritance was suspected in a large family with Charcot-Marie Tooth disease since no male to male transmission was observed, and since the sensory and motor neuropathy was more severe in males than in females. To test linkage to the dominant X-linked Charcot-Marie-Tooth disease (DCMTX) locus in Xq13, genotypes of 19 affected and 19 unaffected individuals from this family were determined for 4 microsatellite markers. Close linkage to mfd66 (DXS453) was found by bipoint analysis (Zmax = 4.8 at theta = 0.00). Multipoint analysis mapped the gene between the androgen receptor and DXYS1. In addition, linkage analysis performed with 11 microsatellite markers, derived from a high density map spanning 16 cM on Xq11-Xq21 revealed 3 new tightly linked loci: afm287zg1 (DXS1216), afm261zh5 and afm207zg5 (DXS995). Multipoint analysis localized the DCMTX gene to a 7.5 cM interval between afm123xd4 (DXS988) and afm116xg1 (DXS986). Combined analysis with these new microsatellites provides a powerful tool for carrier detection because of their high informativity and the small genetic distance (< 10 cM) between the markers flanking the gene. PMID- 7881291 TI - Development of a microsatellite genetic map spanning 5q31-q33 and subsequent placement of the LGMD1A locus between D5S178 and IL9. AB - Limb-girdle muscular dystrophy (LGMD) is a genetically and clinically heterogeneous group of disorders. We previously localized an autosomal dominant form of the disorder (LGMD1A) to chromosome 5q22-31 by linkage analysis in a single large pedigree. After developing a microsatellite genetic map incorporating six loci in q31-33 of chromosome 5 and spanning 35 cM, we have refined the original localization. Using multipoint analysis, LGMD1A is localised to a 7 cM region between the markers IL9 and D5S178 with odds > 1000:1. PMID- 7881292 TI - A scapular onset muscular dystrophy without facial involvement: possible allelism with facioscapulohumeral muscular dystrophy. AB - A dominantly inherited muscular dystrophy with onset in the shoulder girdle and later progression to the lower limbs is described. The disorder was clinically distinguishable from known facioscapulohumeral, scapulohumeral and limb girdle syndromes. A 38 kb allele detected by probe p13E-11 (D4F104S1) segregated with the disease. Linkage analysis gave a maximum lod score of z = 1.61 at theta = 0.01 with the 4q35 markers D4S184 (affected only analysis z = 1.20 at theta = 0.01) suggesting probable allelism with facioscapulohumeral muscular dystrophy. PMID- 7881293 TI - Evidence of two mechanisms of prostaglandin release in an in vitro model of muscle damage. Possible therapeutic implications. AB - In spite of recent progress, treatment of muscle disease based on specific gene therapy is not yet available. An alternative approach is to develop treatment which affords non-specific protection against general factors involved in cell damage. This approach is used effectively to prevent neuronal damage in experimental brain ischemia in animals and has been proposed for human trials. The most effective intervention is the use of mild (35 degrees C) hypothermia. An in vitro model to study muscle cell damage employs the rat epitrochlearis muscle exposed to low concentrations of 2:4-dinitrophenol, an uncoupler of oxidative phosphorylation. The efflux of prostaglandin E2 (PGE2) from the muscle is used as an indicator of muscle damage. We now show that there are two types of PGE2 release. "Basal" efflux gradually declines with decreasing temperatures and is not affected by removal of calcium from the medium. The efflux of PGE2 in response to metabolic stress is dependent on the presence of calcium and is abolished by mild hypothermia of 35 degrees C. The latter effect suggests that cell death is muscle and neurons have features in common and that muscle may be a useful tissue in which to investigate this phenomenon further. PMID- 7881294 TI - Calcitonin gene-related peptide-like immunoreactivity, in botulinum toxin paralysed rat muscles. AB - Changes in calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) at the motor endplates of botulinum toxin-paralysed rat muscles were investigated using immunohistochemistry. One day following toxin injection, a dramatic increase in CGRP-LI was detected at the motor endplates and within preterminal axons of the soleus and gastrocnemius muscles. The upregulation of CGRP-LI persisted throughout the period during which muscle fibres were paralysed and new neuromuscular junctions were being formed by the growing sprouts. Decline of CGRP LI at the motor endplates coincided with clinical recovery. Both up- and down regulation of CGRP-LI took place earlier in the soleus than in the gastrocnemius muscle. Up-regulation of CGRP-LI was also detected in a subpopulation of motor axons in the sciatic nerves and in the spinal motor neurons innervating the paralysed muscles. These results indicate that levels of CGRP are regulated, at least partly, by changes in the target innervation. They also suggest an important role for CGRP in the regenerative processes following muscle paralysis. PMID- 7881295 TI - The natural history of type I (severe) spinal muscular atrophy. AB - The clinical features of 36 patients who satisfied the diagnostic criteria for type I (severe) spinal muscular atrophy (Werdnig-Hoffmann disease) are reported. Survival data for both the whole cohort and for groups within the cohort subdivided on the age of onset are presented. These data suggest that the patients with onset at birth or within the first 2 months of life have a more uniformly poor prognosis with earlier death. This is of potential importance in any therapeutic trials in the future whose outcome may be based on length of survival. PMID- 7881296 TI - Bethlem myopathy: early-onset benign autosomal dominant myopathy with contractures. Description of two new families. AB - Bethlem myopathy is an apparently rare early-onset benign autosomal dominant limb girdle myopathy with contractures of the fingers. To determine whether this disorder is unrecognized rather than rare we used muscle computerized tomography (CT) and isokinetic muscle testing and assiduously sought contractures of the fingers in relatives of two patients with the disease. CT showed that muscle impairment was mild but more diffuse than clinically apparent and showed an unexpected progressive degeneration of lumbar paravertebral muscles. The isokinetic test showed that the quadriceps was more involved that the hamstrings. In addition we found that contractures of the last four fingers progressed centripetally with age from the distal interphalangeal joints to the wrist. As a result we proved that 15 of the 21 examined subjects had the disease, 7 of them being unaware that anything was amiss. Careful examination may reveal that Bethlem myopathy is more common than is now thought. PMID- 7881297 TI - Neonatal nemaline myopathy with abundant intranuclear rods. AB - A term hypotonic female infant was born to a primigravida mother. The infant required mechanical ventilation from birth until death at 5 weeks of age. An elevated serum creatine kinase of 1300 IU l-1 lead to a quadriceps muscle biopsy at 3 days of age. The biopsy showed numerous intranuclear inclusions on light microscopy. Electron microscopy revealed the inclusions to be rod (nemaline) bodies and were located in 80% of the muscle nuclei. Cytoplasmic rod bodies were also present in 50% of the muscle fibers, often arising from Z discs. The intranuclear rods were more than ten times larger than the cytoplasmic rods. There have been eight reported cases of abundant intranuclear rods in nemaline myopathy: three adult onset; one childhood onset; and four neonatal (including this case). Six of the cases (all of the neonatal and two adult onset) died due to respiratory failure and pneumonia. While intranuclear rods are unusual in nemaline myopathy, they occur in both adult and neonatal cases, and their presence is often associated with a fatal outcome. PMID- 7881298 TI - The wasted leg syndrome, a single fibre electromyographic study of arms and legs. AB - Single fibre electromyography (SFEMG) was performed on 11 patients with the wasted leg syndrome. Five were of South Asian origin and the others Chinese. In most cases the disorder progressed for about 5 yr before becoming static or very slowly progressive. The SFEMG fibre density was increased similarly in both the affected and less affected leg, but was normal in the arms except for a few longstanding cases. The limited extent of clinical and electrophysiological abnormalities suggests that the wasted leg syndrome is a distinct entity. PMID- 7881300 TI - Neuromuscular disorders: gene location. PMID- 7881299 TI - The natural history of severe spinal muscular atrophy--further evidence for clinical subtypes. PMID- 7881301 TI - Mitochondrial encephalomyopathies: gene mutation. PMID- 7881302 TI - Info. A legal information sheet for nurses. Negligence. PMID- 7881303 TI - Plans continue for a provincial nursing education program. PMID- 7881305 TI - Personal perspectives on rural nursing. PMID- 7881304 TI - Nursing experiences in rural Saskatchewan. PMID- 7881306 TI - Rural nursing. Handicapped farmers program: an informational update. PMID- 7881307 TI - The multiskilled practitioner and client-focused care. PMID- 7881308 TI - Strategies to stroke prevention: nurse facilitation. PMID- 7881309 TI - New CNATS exam to begin in August. PMID- 7881310 TI - How important is vitamin K at birth? PMID- 7881311 TI - Illa Hammond. Interview by Ina May Gaskin. PMID- 7881312 TI - Culture and birth: the technocratic imperative. PMID- 7881313 TI - Judy Mentzer. Interview by Ina May Gaskin. PMID- 7881315 TI - C-sections on demand. PMID- 7881314 TI - A rural midwife's practice makes a difference. PMID- 7881316 TI - Another suggestion for uterine prolapse. PMID- 7881317 TI - MANA, ACNM & IWG: prospects for unity. PMID- 7881318 TI - Diet and disease. AB - Dietary factors are influential in the most important public health problems of Western society. Together, diseases such as coronary heart disease and stroke, cancers, and the effects of osteoporosis constitute the most common causes of disability and death. All of these diseases are multifactorial in their aetiology, but there remains some potential for disease prevention by dietary manipulation. For coronary heart disease and stroke, dietary factors play important roles in modulating blood lipids and their propensity for oxidation. In addition the propensity for thrombosis can be influenced by dietary factors, particularly by the inclusion of fish oils. For cancers, the influence of the diet is less certain, but fats, fibre and antioxidant vitamins and minerals have been most closely scrutinised. In osteoporosis the most important dietary factor is the availability of calcium. This is important both in building peak bone mass and in minimising bone loss later on. There is also some evidence that dietary factors can be helpful in minimising the symptoms of disease. Most notably, the inflammatory process in rheumatoid arthritis can be modified by fish and evening primrose oils, although these effects are relatively mild compared with standard pharmaceutical treatments. PMID- 7881319 TI - Recovery of Escherichia coli 0157:H7 from mixed suspensions: evaluation and comparison of pre-coated immunomagnetic beads and direct plating. AB - Escherichia coli O157:H7 has become an important enteropathogen, causing sporadic outbreaks of haemorrhagic colitis. However, it has not so far been isolated from suspect foods, which may be due to low numbers, sub-lethal injury, or overgrowth by other organisms. Immunomagnetic separation could provide an answer to these problems. The technique utilises antibody-coated magnetic polymer beads and is considered fast, safe, sensitive and reproducible. Commercially produced polymer beads coated with a polyclonal antibody were standardised and compared with direct plating to maximise recovery of Esch. coli O157:H7 from mixed suspensions. An increase in sensitivity was found, but this was offset by a loss of specificity. PMID- 7881320 TI - Detection of HCV-RNA in the blood donor population of Yorkshire. AB - The purpose of this study was to develop a reliable and specific polymerase chain reaction (PCR) for the detection of hepatitis C virus-ribonucleic acid (HCV-RNA) in the plasma of blood donors who attend the Yorkshire Regional Transfusion Centre. These donors had previously had a positive or indeterminate recombinant immunoblot assay (RIBA) result. For increased sensitivity of reaction and greater specificity of product, a 'nested-primer' PCR was used. One hundred and ninety two samples were examined, of which 18 were RIBA-positive and HCV-RNA was detected in 15 (83%) of them. Of the 174 RIBA indeterminates only one (0.6%) had detectable HCV-RNA. The rate of HCV-RNA detection in fresh and archive samples was compared and found to be greater with the fresh samples. PMID- 7881321 TI - Malnutrition: folate and cobalamin deficiency. AB - Malnutrition of folate and cobalamin occurs on a world-wide scale. Millions of individuals, for a variety of cultural, religious and socio-economic reasons, ingest less than the daily amounts required to maintain body stores. Assessment of intake depends on the population under study, method of food preparation and assay technique. Up to 90% of folate may be destroyed by cooking and, although less, significant amounts of cobalamin can also be lost in this way. Estimates of the proportion of both vitamins absorbed from a mixed diet vary, but may be as little as 50%. The need for supplementation is more common with folate than cobalamin. However, recent advances have highlighted subtle sub-clinical metabolic changes in some groups, particularly the elderly. Further investigation into their requirements is indicated. New assays for metabolites of cobalamin and folate are highly sensitive but lack specificity and are not readily available. PMID- 7881322 TI - The role of nutrition in osteoporosis. AB - Osteoporosis-related bone fractures are a significant cause of mortality and morbidity, with women being particularly affected. Osteoporosis is a condition of bone fragility resulting from micro-architectural deterioration and decreased bone mass; adult bone mass depends upon the peak attained and the rate of subsequent loss; each depends on the interaction of genetic, hormonal, environmental and nutritional factors. An adequate supply of calcium is essential to attain maximum bone mass, and adult intakes below about 500 mg/day may predispose to low bone mass. Supplementation with calcium may conserve bone at some skeletal sites, but whether this translates into reduced fracture rates is not clear. Chronically low intakes of vitamin D--and possibly magnesium, boron, fluoride and vitamins K, B12, B6 and folic acid (particularly if co-existing)- may pre-dispose to osteoporosis. Similarly, chronically high intakes of protein, sodium chloride, alcohol and caffeine may also adversely affect bone health. The typical Western diet (high in protein, salt and refined, processed foods) combined with an increasing sedentary lifestyle may contribute to the increasing incidence of osteoporosis in the elderly. PMID- 7881323 TI - Putative role of dietary trace elements in coronary heart disease and cancer. AB - Relatively little attention has been given to the role of dietary trace elements in oxidative processes or in the aetiologies of chronic disease processes. Iron and copper are pro-oxidants in vitro, but there is now compelling evidence that adequate body copper status is required to maintain antioxidant defences in vivo. Epidemiological evidence linking measures of high iron nutritional status with both coronary heart disease (CHD) and cancer is accumulating, although there are few mechanisms implicating iron in these disease processes apart from acting as a pro-oxidant. In contrast, low copper nutritional status may produce pro-oxidant effects and experimental evidence, especially from animal models of CHD, suggests that copper has an involvement in disease mechanisms which is much wider than simply an involvement in maintaining oxidant/antioxidant balance. Zinc is considered to have antioxidant effects in vivo but the role of zinc as an antioxidant, or in CHD and cancer processes, is presently unclear. Although selenium has for some time been recognised as an antioxidant nutrient, epidemiological data gathered to date linking this trace element with either CHD or cancer are inconsistent. PMID- 7881324 TI - Diet and immune function. AB - Adequate human nutrition is essential to maintain all normal physiological functions including defence of the self. Controversy exists about the precise constituents of diets optimal for all stages in the human life-span. Dietary composition may also need to be altered under such stressful conditions as infection or recovery from major surgery. Understanding how specific nutrients can alter immune responses may add to the quality of human lives by minimising the impact of disease morbidity and mortality. Dietary modification also offers hope of new therapeutic regimens for human diseases. PMID- 7881325 TI - Can dietary oats promote health? AB - Current consumption levels of oat products are low. However, oats are a nutritious foodstuff, supplying protein of relatively good quality and significant quantities of vitamins and minerals. As a bland and nutritious foodstuff, oats are valuable for the nutrition of infants and the sustenance of adults. Oats are generally consumed as oatmeal or rolled oats, but oat bran has become available in recent years. In addition to their nutritional attributes, dietary oat products exert a number of physiological effects that may be beneficial in the prevention or amelioration of pathophysiological states, including improvements in gastro-intestinal function, modulation of glucose metabolism, and decreasing blood cholesterol status. The latter effects have attracted considerable attention and a critical review of the data indicates that dietary oats have the ability to lower blood cholesterol and that they are most effective at high dose levels in hypercholesterolaemic individuals. Although the soluble fibre, beta-glucan gum appears to be the major hypocholesterolaemic agent, its mode of action is not fully understood. PMID- 7881326 TI - Nutrition and the ageing process. AB - Ageing is a complex biological phenomenon, and many of the contributing mechanisms have not yet been identified. With increasing age there is an increased risk of development of a number of age-related pathologies. In recent years experimental evidence has highlighted the role of free radical-induced biomolecule damage in the pathogenesis of such diseases. It may be that antioxidant intervention, by inhibiting or reducing free radical toxicity, could alleviate or delay the symptoms of ageing and chronic disease. In this article some of the scientific evidence in support of this is presented. In addition, other dietary factors which have been shown to be of importance for the prevention/delay of onset of age-related pathologies are discussed. PMID- 7881327 TI - Antioxidants, nutritional supplements and life-threatening diseases. AB - Antioxidants are a complex and diverse group of molecules that protect key biological sites from oxidative damage. They usually act by removing or inactivating chemical intermediates that produce the ultimate oxidant. Different sites in the body have evolved to use highly specialised strategies to deal with free radicals and other reactive oxygen intermediates. Recent epidemiological evidence suggests that the development of life-threatening disease, such as cancer and heart disease, is linked to our dietary intake of micronutrients including antioxidants. Modification of dietary habits together with supplementation may provide a simple yet profound way to reduce deaths from these two major diseases. Sound scientific evidence to support a curative role for antioxidants in life-threatening diseases, however, is lacking. PMID- 7881328 TI - Immunoassay of gonadotropins using a fully-automated benchtop analyser. AB - We assessed the analytical performance of the Abbott IMxTM immunoassay analyser for total beta human chorionic gonadotropin (Beta hCG), follicle-stimulating hormone (FSH) and luteinising hormone (LH). The within-run CVs for various analyte concentrations were 2% to 6% while those for between-run imprecision in routine assay ranged from 4% to 10%. IMxTM values correlated well with radioimmunoassay for beta hCG, and immunoradiometric assay for FSH and LH; the correlation coefficients (r) were 0.97, 0.99 and 0.98 for total beta hCG, FSH and LH respectively. The average sensitivities were approximately 3.1, 0.2 and 0.5 iu/l for beta hCG, FSH and LH, respectively. Sample carry-over was not detected and there was negligible cross-reaction between LH and beta hCG in the respective assays. The automatic sample dilution protocol for beta hCG was superior to the manual procedure. The IMxTM is easy to operate and is able to process 24 samples in 40-45 minutes. PMID- 7881329 TI - The eye and its diseases in antiquity. A compilation based on finds from ancient times. PMID- 7881330 TI - Modelling the mechanical response of skin in vivo using the Bossinesq and the Michell stress functions. AB - Local strains acting across an area of skin loaded uniaxially in vivo are converted to stresses using the standard elastic formulae. The stress values are compared to those obtained using the classical Bossinesq and Michell stress functions. The results indicate that these functions are capable of describing the response of the skin, both in the low load and the high load regions. PMID- 7881331 TI - Biaxial tension test of human skin in vivo. AB - The response of human skin to biaxial stretch tests in vivo was investigated and compared to the response to uniaxial tension. The results obtained illustrate the nonlinear, anisotropic, and viscoelastic (time-dependent) properties of skin under biaxial stretch. Preconditioning in the load-extension response was found not to be prominent. The results also suggest that the response of skin to a biaxial stretch in vivo is qualitatively similar to that in vitro. Values of the terminal stiffness and limit strain of skin under a biaxial stretch are found. PMID- 7881332 TI - Morphological change in myocardium in goat recovered from profound left ventricular failure with cardiac assist device. AB - With left ventricular assist device (LVAD) pumping, goats having induced-heart failure were salvaged. LVAD was weaned off when the heart seemed to recover, and animals were kept alive for about 1 month after the pump removal. After termination of the experiments, infarction area was 10 to 50% of the left ventricular wall including the septum. The longer pumping period against severe infarction resulted in the thinner wall thickness of normal myocardial area. The myocyte diameter (Dm) was microscopically measured in 3 layers: sub-epicardium, middle myocardium and sub-endocardium. Subendocardial Dm was largest, and followed by Dm in middle myocardium, and then Dm in subepicardium. These results coincided with results obtained from a control-heart experiment except that Dm in the normal area of recovered hearts was thicker. The relation between Dm and left ventricular external mechanical work computed from left ventricular pressure volume relation showed an adaptive control mechanism of myocardium. PMID- 7881333 TI - A parametric finite element analysis study of the stresses in an endosseous implant. AB - The finite element analysis method was used to obtain the stresses in the various structures in an endosseous implant-contiguous bone construct using a two dimensional idealization. The results were obtained as a function of the materials used for the post and the crown of the implant. It is shown that these stresses are critically dependent on the post material (for a given crown material). The clinical significance of the results is discussed. PMID- 7881334 TI - Effects of Sr-hydroxyapatite microcrystal on cultured cell. AB - Strontium-hydroxyapatite microcrystals (Sr-HAp sol) were produced by a wet method at room temperature with ultrasonic irradiation and were applied to MC3T3-E1, ROS, and L cells for periods of 2, 4, and 6 days in vitro. The effect on cell growth, the variation of LDH and Ca contents in the media, and attachment between cell and microcrystal were investigated. Sintered Sr-HAp and HAp sol were used as controls. A slight inhibitory effect of Sr-HAp sol on cell growth was found. The degree of inhibition was nearly the same as HAp sol. However, it was stronger than sintered Sr-HAp. The contents of LDH in the media increased with the degree of cell inhibition, and the contents of Ca in the media decreased from the initial stage of cell-sol contact. A good attachment of Sr-HAp sol to cultured cells was seen by phase-contrast microscopy and SEM. PMID- 7881335 TI - The role of obesity and weight fluctuations in the etiology of renal cell cancer: a population-based case-control study. AB - The causes of renal cell cancer (RCC) are poorly understood. Besides smoking, obesity remains the only risk factor that is fairly well established. The association between obesity and RCC appears stronger and more consistent in women than in men. We investigated the question of whether this apparent sex difference could be explained by repeated weight changes (weight cycling), less physical exercise, or pharmacological treatment of obesity in women. Structured face-to face interviews were carried out with 379 (70% of all eligible) incident cases of RCC and 353 (72% of eligible) controls. The relationships between RCC and adult height, weight, and body mass index (BMI), defined as weight/height, were analyzed. Odds ratios (ORs) were estimated through logistic regression. No association was found between adult height and RCC. In men, weight and BMI appeared at most to be weakly related to risk of RCC. In women, higher adult weight and BMI (usual, highest, and lowest) and also high BMI at ages 30, 40, and 50 years were consistently associated with a significantly increased risk of RCC. Women with an usual adult BMI in the top 5% had a nearly 3-fold increased risk of RCC [OR, 2.67; 95% confidence interval (CI), 1.02-7.01]. Compared with individuals with no weight-loss periods, 2 or more such periods implied an OR of 0.96 (95% CI, 0.32-2.90) in men and 3.87 (95% CI, 1.20-12.45) in women. Physical activity at work reduced the risk of RCC in men but not women. Regular use of diet pills containing amphetamine was associated with an increased risk of RCC (OR, 4.06; 95% CI, 1.35-12.22).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881336 TI - Early adulthood physical activity and colon cancer risk among Wisconsin women. AB - Frequency of strenuous activity during ages 14-22 was ascertained retrospectively from 536 Wisconsin women with newly reported diagnoses of colon cancer and 2315 controls randomly selected from Wisconsin driver's license and Medicare beneficiary lists. Thirty-five % of cases and 34% of controls reported strenuous activity during this period of early adulthood. After adjusting for age, family history of large bowel cancer, history of screening sigmoidoscopy, and body mass index in logistic regression models, women who reported any strenuous activity were at a similar risk of colon cancer as women who did not report activity [odds ratio (OR), 1.02; 95% confidence interval (CI), 0.82-1.27); no significant decrease in risk was seen with increase in frequency of activity (P for trend = 0.84). Results were similar for the right and left colon subsites. These data suggest that early adulthood physical activity may not confer the same protective effect that has been observed with recent physical activity. PMID- 7881337 TI - Association of paternal diagnostic X-ray exposure with risk of infant leukemia. Investigators of the Childrens Cancer Group. AB - Whether low level radiation exposure before conception increases the risk of leukemia in offspring has been much debated. No study has specifically evaluated the effect of parental preconception diagnostic X-ray exposure in the development of leukemia among infants. Mothers of 302 infant leukemia cases (diagnosed at < or = 18 months of age) and 558 individually matched regional controls, and fathers of 250 cases and 361 controls, were independently interviewed to obtain information on X-ray exposures. Paternal preconception X-ray exposure was associated with an increased risk of infant leukemia, higher risks being linked to exposures closer to conception. X-ray related leukemia risk varied with exposure site and histopathological type, the highest risk being for acute lymphocytic leukemia related to two or more X-rays of the lower gastrointestinal (GI) tract and lower abdomen (odds ratio, 3.78; 95% confidence interval, 1.49 9.64). A positive association was observed between acute lymphocytic leukemia and number of paternal X-rays of the lower GI and lower abdomen (trend test, P < 0.01), upper GI (P = 0.04), and chest (P = 0.08). Exposures of head and neck and limbs were unrelated to risk. The risk of acute myelogenous leukemia was unrelated to paternal X-ray exposure, except for a marginally significant association (trend test, P = 0.07) for upper GI X-rays. No consistent association between maternal X-ray exposure and infant leukemia was observed. The results of this study suggest that paternal low level radiation exposure before conception is associated with an increased risk of infant leukemia, although the nature of this association needs to be further evaluated. PMID- 7881338 TI - Fatherhood and distal adenomas of the large bowel: a study of male self-defense officials in Japan. AB - Parity has been studied extensively as a risk factor for colorectal cancer but has not been definitively shown to be associated with altered risk. In a few studies, risk of colorectal cancer in childless men has been compared to risk in men with children, but results have not been consistent. We analyzed the association of fatherhood with risk of colorectal adenomas in male self-defense officials (ages 49-55) in Japan. The study participants received a preretirement health examination including flexible sigmoidoscopy at Self-Defense Forces hospitals in Japan from January 1991 through December 1992. The examinations identified 265 cases with rectal or sigmoid adenomas and 1480 controls with normal examinations up to 60 cm from the anus. Data on marital status, number of children, long-term work assignment away from wife and children, and other lifestyle variables were obtained by means of a self-administered questionnaire prior to physical examination. Multiple logistic regression analysis assessed the risk of adenomas in relation to number of children, marital status, long-term work assignment away from family, and military rank, with adjustment for cigarette smoking, alcohol intake, dietary variables, body mass index, and recreational physical activity. In this relatively homogeneous group, more than 98% of both cases and controls were currently married, and more than 93% had children. The adjusted odds ratio for the association of adenomas with fatherhood was 0.4 (95% confidence interval, 0.2-0.8). Marital status and work assignment away from the family were not associated with adenoma risk. These findings suggest that colorectal adenomas and perhaps cancer risk may be associated with childlessness in men. PMID- 7881339 TI - Cutaneous melanoma in women: ovulatory life, menopause, and use of exogenous estrogens. AB - Factors related to menopause and use of exogenous hormones other than p.o. contraceptives were examined in 452 women ages 25-59 who were diagnosed with cutaneous malignant melanoma. Control subjects for this population-based study in the San Francisco Bay Area were 930 women of the same age. An increased risk was observed for superficial spreading melanoma (SSM) in women who reached natural menopause after age 55 [odds ratio (OR), 3.6; 95% confidence interval (CI), 1.1 11.1], and for women who had had a bilateral oophorectomy within 9 years of their diagnosis with SSM (OR, 2.2; CI, 1.1-4.5). A somewhat elevated risk of melanoma after natural menopause or hysterectomy was no longer statistically significant after adjustment for exogenous hormone use. Prolonged use of p.o. exogenous hormones after hysterectomy for women who had retained at least one ovary was associated with an increased risk of SSM (OR, 5.4; CI, 1.5-19.3), and use of these products for fewer than 5 years after bilateral oophorectomy also was associated with an elevated risk of SSM (OR, 2.9; CI, 1.0-7.8). Conjugated estrogen use was associated with somewhat elevated risks for SSM after hysterectomy with one ovary retained (OR, 2.7; CI, 0.97-7.3) and after hysterectomy with bilateral oophorectomy (OR, 2.1; CI, 0.86-5.0). There was a suggestion of a trend for increased risk of SSM with increased dosage of conjugated estrogens after hysterectomy (P for trend = 0.07). Use of vaginal creams that contained estrogen also was associated with an increased risk of SSM (OR, 1.8; CI, 1.0-3.3). PMID- 7881340 TI - Fluorescence quantification of aflatoxin N7-guanine adducts. AB - Increasingly sensitive assays are needed to understand and evaluate the effects of chemical exposures on individuals and populations. Several assays have been developed to measure the environmental dietary carcinogen, aflatoxin, and its metabolites in biological specimens. One, the 8,9-dihydro-8-(N7-guanyl)-9-hydroxy aflatoxin B1 nucleic acid adduct, has been shown to be both highly correlated with exposure and a strong predictor of carcinogenic outcome. Assays with increased sensitivity for this chemical adduct would be beneficial. Therefore, we have developed a hydrolysis reaction for the adduct found in urine, utilizing HCI acid and heat. Subsequently, quantification of the fluorescent metabolites produced can be obtained by either synchronous fluorescence spectrophotometry or high pressure liquid chromatography with fluorescence detection. The detection of lower levels of the adduct could prove helpful in the evaluation of risk in populations with lower exposures, such as those in chemoprotection trials or occupationally exposed groups. PMID- 7881341 TI - Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501A2 and putative exposure to food-borne heterocyclic amines increase the risk for colorectal cancer or polyps. AB - The metabolic activation of food-borne heterocyclic amines to colon carcinogens in humans is hypothesized to occur via N-oxidation followed by O-acetylation to form the N-acetoxy arylamine that binds to DNA to give carcinogen-DNA adducts. These steps are catalyzed by hepatic cytochrome P4501A2 (CYP1A2) and acetyltransferase-2 (NAT-2), respectively, which are known to be polymorphic in humans. On the basis of this proposed metabolic activation pathway, patients at greatest risk to develop colorectal cancer or nonfamilial polyps should be those who possess both the rapid NAT-2 and rapid CYP1A2 phenotypes and are exposed to high dietary levels of carcinogenic heterocyclic amines. Using a method that involves caffeine administration and high pressure liquid chromatographic analysis of urinary metabolites, we have determined the CYP1A2 and NAT-2 phenotypes of 205 controls and 75 cancer/polyp cases. Exposure information was obtained using a dietary and health habits questionnaire. Both the rapid CYP1A2 and rapid NAT2 phenotypes were each slightly more prevalent in cases versus controls (57% and 52% versus 41% and 45%, respectively). However, the combined rapid CYP1A2-rapid NAT-2 phenotype was found in 35% of cases and only 16% of the controls, giving an odds ratio of 2.79 (P = 0.002). Univariate analysis of the questionnaire indicated that age, rapid-rapid phenotype, and consumption of well done red meat were associated with increased risk of colorectal neoplasia. Furthermore, a logistic regression model that included age (as a continuous variable), consumption of well done red meat, and rapid-rapid phenotype as independent covariates gave odds ratios of 1.08, 2.08, and 2.91, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881342 TI - Demonstration of a field defect in gastric intestinal metaplasia by biological marker analysis. AB - Gastric intestinal metaplasia (GIM) is a precursor lesion for gastric cancer. It most frequently involves the antrum and the angularis. At endoscopy, it is not possible to visually distinguish GIM from normal stomach. Furthermore, GIM frequently has a patchy distribution with areas of metaplasia coexisting with adjacent areas of other histologies, including normal stomach. In this study we sought to determine whether a "field defect" could be demonstrated in subjects with GIM, involving the entire region of the stomach. The biologic markers tested were ornithine decarboxylase (ODC) activity and bromodeoxyuridine labeling index (LI). Antral biopsies were obtained from 13 subjects with known GIM and 9 controls (no GIM based on multiple biopsies and absence of methylene blue staining). Three adjacent biopsies were obtained for ODC, LI, and histology. Group I consisted of a set of 3 biopsies from the 9 controls. In the 13 subjects with GIM, 2 sets of 3 biopsies were taken with methylene blue guidance in an attempt to obtain both GIM-free (group II) and GIM-containing (group III) tissue. ODC activities were markedly and statistically significantly (P = 0.0001) elevated in groups II and III versus group I; the mean +/- SDs were 0.075 +/- 0.117 for group I, 1.20 +/- 0.83 for group II, and 1.14 +/- 0.76 for group III. Group II versus Group III values were not different (P = 0.979). LI was less discriminatory with more overlap between the groups. The highest LI was in group II, which was significantly different from group I (P = 0.014) and group III (P = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881343 TI - Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? AB - Several aspects of Western diets, alcohol use, and exercise patterns which are related to the risk of colorectal cancer have systemic effects in common. Those which increase the risk of colorectal cancer are positively associated with serum triglycerides and plasma glucose; those which decrease risk are negatively associated with serum triglycerides and plasma glucose. These observations suggest the hypothesis that serum triglycerides and/or plasma glucose may themselves be associated with colorectal cancer risk. Evidence for associations between colorectal neoplasia and triglycerides and glucose comes from two recent studies of adenomatous polyps, presumed precursors for colorectal cancer, and from previous studies of diabetes and cancer. In addition, three randomized trials, one in humans and two in animal models, suggest that diets which would be expected to increase serum triglycerides and plasma glucose increase the levels of cellular indicators of colorectal cancer risk. Biological mechanisms explaining associations between colorectal neoplasia and serum triglycerides and/or plasma glucose might involve luminal or circulatory effects: (a) triglycerides and/or glucose may be associated with fecal bile acids, acids which are positively associated with colorectal cancer risk in epidemiological studies and which promote colorectal cancer in animal models; (b) serum triglycerides and/or plasma glucose might influence circulating hormones, such as insulin, which might themselves be involved in cancer development; (c) serum triglycerides and/or plasma glucose might be indicators of energy available through the circulation for neoplastic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881345 TI - Long-term vitamin A does not produce clinically significant hypertriglyceridemia: results from CARET, the beta-carotene and retinol efficacy trial. AB - Retinol and retinyl palmitate in the moderate doses tested in chemoprevention trials produce only a negligible increase in serum triglyceride levels. The effect is nonprogressive and is not associated with the kind of exaggerated response reported for interacting factors such as presence of diabetes mellitus and/or high baseline values for serum triglyceride concentration. These findings seem to represent an advantage for safety of retinol in relation to isotretinoin (13-cis-retinoic acid). PMID- 7881344 TI - Biomarkers in upper aerodigestive tract tumorigenesis: a review. AB - Because therapeutic efforts such as surgery, radiotherapy, and chemotherapy have only marginally improved the 5-year survival rate from cancers of the upper aerodigestive tract (including head and neck and lung cancers) over the past 2 decades, chemoprevention has become an important strategy in reducing the rates of incidence and mortality of these cancers. However, chemoprevention trials have been hampered by serious feasibility problems; they require large numbers of subjects and long-term follow-up for accurate determination of cancer incidence and they are very costly. Because the use of intermediate end points would reduce the duration and costs of these studies, biomarkers that could serve as such end points have recently become a subject of great interest. With the strengthening of the assumption that tumorigenesis is a multistep process of transformation from normal tissues to malignant lesions, there has been a great effort to examine each of these steps for genetic and/or phenotypic alterations that might be candidates for such biomarkers. These candidates include genomic markers, certain specific gene alterations, such as tumor suppressor genes, oncogenes, growth factors and their receptors, proliferation markers, and differentiation markers. In this review, we describe several genomic markers, including micronuclei, chromosomal alterations, and specific genetic markers, e.g., the ras gene family, erb B1, int-2/hst-1, and p53 tumor suppressor gene. We also review the proliferation markers, including proliferating cell nuclear antigen, and squamous cell differentiation markers, including keratins, involucrin, and transglutaminase 1. These biomarker candidates have the potential to be important adjuncts to the development of new chemopreventive agents and to the rational design of future intervention trials. However, we can not overemphasize that these markers need to be validated in clinical trials; only then can they replace cancer incidence as the sole end point for chemoprevention trials. PMID- 7881346 TI - Collaborative interdisciplinary studies of p53 and other predisposing genes in Li Fraumeni syndrome. PMID- 7881347 TI - Fludarabine in lymphoproliferative disorders: the Royal Marsden Hospital experience. AB - Fludarabine 25 mg/m2 was given on five consecutive days every four weeks to 85 patients with B- and T-cell malignancies. The median number of courses given was five. All patients except one had received previous chemotherapy. The overall response rate in non-Hodgkin's lymphoma (NHL) was 50% (five complete responses (CR) and 19 partial responses (PR)). The response rate in chronic lymphocytic leukemia (CLL) was 43% (four CR and 12 PR). Responses were seen in all groups of B-cell malignancies, but no T-cell malignancies (n = 4) responded. The median duration of CR has not been reached and the median duration of PR was 14 months for NHL and 16 months for CLL. The median survival from starting fludarabine for patients who achieved a CR or PR in NHL has not been reached and the median duration of PR in CLL was 23 months. The median duration of survival in non responders was five months. Fludarabine was well tolerated and the main toxicity was myelosuppression. Our results suggest that even in patients who have never responded to any chemotherapy, regardless of the number of treatment regimens previously given, there is a 36% chance of response. In addition, this is the first report of fludarabine activity in Franklin's disease. PMID- 7881349 TI - A career in retrospect: a hope for the future. PMID- 7881348 TI - Fludarabine inhibits DNA replication: a rationale for its use in the treatment of acute leukemias. AB - Fludarabine is a prodrug that must enter cells and be phosphorylated to the nucleoside triphosphate, F-ara-ATP, to elicit biological activity. F-ara-ATP serves as an inhibitory alternative substrate in several key processes involved in DNA synthesis. The enzymes required in DNA synthesis and affected by F-ara-ATP are ribonucleotide reductase, DNA primase, DNA polymerases, 3'-5' exonuclease activity of DNA polymerases delta and epsilon, and DNA ligase I. The action of fludarabine on DNA replication provides a compelling rationale to use this agent for leukemias where target cells are actively synthesizing DNA, for example acute myelogenous leukemia. Additionally, the role of F-ara-ATP to potentiate the activity of deoxycytidine kinase makes it an appropriate candidate to use in combination with other nucleoside analogs which require deoxycytidine kinase for their activation. The present article reviews the effect of fludarabine on enzymes involved in DNA synthesis and the role of fludarabine in combination with arabinosylcytosine for the treatment of diseases other than indolent leukemias. PMID- 7881350 TI - Eutectic mixture of local anesthetic cream--topical anesthesia for extracorporeal shock wave lithotripsy. AB - A 44-year-old man presented with a history of sudden onset left flank pain, accompanied by nausea and microhematuria. The diagnosis of ureteropelvic junction calculus was made and the patient was scheduled for extracorporeal shock wave lithotripsy (ESWL). ESWL uses an electrical spark to generate a shock wave that is focused on a stone in the ureter or kidney. The shock waves mechanically stress and crush the stone, eliminating the need for manipulation or open procedure. The pain of ESWL is caused by skin sensation. Eutectic mixture of local anesthetics (EMLA) cream (2.5% lidocaine and 2.5% prilocaine) has been used as a topical anesthetic on intact skin for various minor procedures. Studies have shown that it is effective in dramatically decreasing or eliminating the pain of ESWL. The use of topical EMLA as an anesthetic management technique for a patient undergoing ESWL is described. PMID- 7881352 TI - Probable succinylcholine-induced hyperkalemia in a trauma victim after recent benign anesthetics with succinylcholine. AB - Throughout its pharmacological history in anesthesia practice, succinylcholine has been notorious for its role in causing life-threatening hyperkalemia. Normally the serum potassium level will increase .5 to 1.0 mEq/L because of a sustained opening of the receptors in the neuromuscular junction and release of myoplasmic potassium. However, in certain patients the drug will result in a much higher level of serum potassium. The literature points out numerous conditions that predispose particular patients to this exaggerated intensification of potassium leakage from within the cell. Traumatized, neuromuscular diseased, infected, exsanguinated, acidotic, and closed head injury patients among this list. This case report describes a trauma patient requiring numerous orthopedic repairs in a relatively short period of time. He received succinylcholine on three separate occasions within a 20-day span without any untoward effects. However, during his sixth surgery and the fourth administration of succinylcholine, he developed ventricular fibrillation requiring defibrillation and cardiopulmonary resuscitation before converting to a sinus tachycardia. After ruling out other causes of the arrhythmia, the most probable one was hyperkalemia. A possible explanation of this probable succinylcholine-induced hyperkalemia may have been a combination of the trauma, tissue wasting, infection, immobility, or acute respiratory acidosis. The potassium elevation was treated successfully with hyperventilation, calcium chloride, sodium bicarbonate, glucose, and insulin. The patient recovered without complications and was later discharged to home. Succinylcholine definitely has its use in anesthesia, but it is imperative for the provider to be discriminatory in its administration. An all encompassing history is paramount to discover any hidden rationale not to use succinylcholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881351 TI - Blood component therapy and changing transfusion triggers. AB - Transfusion trigger points and appropriate blood component therapy must be continuously evaluated by the anesthesia team during a surgical procedure. This article examines the composition of homologous blood, the storage of blood products, and transfusion reactions. Additionally, the incidence of transfusion transmitted infections is explored. Finally, a review of the current recommendations for transfusions in the clinical setting is provided. PMID- 7881353 TI - The epidural blood patch--current practices and concerns. AB - Post dural puncture headache is a common sequelae of spinal and, sometimes, epidural anesthesia. Since 1960, the practice of placing autologous blood into the epidural space to treat spinal headache has been used with great success. The blood patch can provide immediate symptom relief from spinal headache and repair of the CSF leak, which is the basic mechanism of post dural puncture headache. Discrepancies exist in the literature and in today's common practice regarding technique and timing for this treatment. This is a procedure not without complications and requires caution. Contained herein are recommendations for safe and effective use of the epidural blood patch. Following these procedures, anesthetists will likely see an 85% to 98% immediate cure rate for post dural puncture headache with the fewest possible complications. PMID- 7881354 TI - Equipment failure: who is responsible? PMID- 7881355 TI - Anesthetic drug interactions. PMID- 7881356 TI - Stem cell transplantation: past, present and future. AB - Attempted human allogeneic marrow transplants in the 1950s and 60s were largely unsuccessful. In the past two decades the probability of success has improved steadily depending on the type and stage of disease. Cure rates range from about 90% for nonmalignant diseases transplanted early to 15% for patients with advanced leukemia. Most marrow transplants have involved an HLA matched sibling donor but, more recently, through the National Marrow Donor Program, a matched unrelated volunteer marrow donor can be found for many patients without a family donor. Current research involves new preparative regimens for elimination of malignant cells, better prevention of graft-versus-host disease, and the use of hematopoietic growth factors and cytokines. Autologous transplants, which use the patient's own marrow, are increasing. The hematopoietic stem cell, which is responsible for marrow regeneration after a transplant, has been isolated and characterized. Stem cells for transplantation can now be obtained from the peripheral blood after mobilization of these cells by chemotherapy or hematopoietic growth factors. A variety of technological advances makes it possible to perform transplants with less time in the hospital and a corresponding saving in cost. PMID- 7881357 TI - Hemopoietic stem cells: analysis of some parameters critical for engraftment. AB - In this review four parameters relevant to the grafting of hemopoietic stem cells (HSC) are analyzed: the nature and amounts of grafted HSC, the sources of HSC and the "in vivo" fate of the grafted cells. One may oppose cells with short-term repopulating ability to cells with long-term reconstitutive capacity. The former comprise progenitors, while the latter consist of primitive stem cells, corresponding to murine pre-colony forming units-spleen (pre-CFU-S) (and to some murine CFU-S) or to human pre-colony forming units (pre-CFU). In the mouse, the number of progenitors involved in short-term reconstitution is large, while that of primitive cells operating months after the transplantation is reduced. These results may be extrapolated to humans, suggesting that it is possible to engraft a limited number of genetically modified HSC. However, the administration of large numbers of reconstituting cells appears to be a cautionary procedure, since it should insure polyclonal hemopoiesis, which is the physiological situation in mammals. Besides marrow, peripheral blood from adult patients treated with chemotherapy and growth factors, and cord blood from newborns, are promising sources of HSC. Successful engraftment depends not only on the quality and quantity of HSC, but also on the integrity of the marrow microenvironment. This microenvironment may be impaired by chemo- and radiotherapy, which provides a theoretical basis for the transplantation of stromal cells along with that of HSC. PMID- 7881358 TI - Gene transfer into hematopoietic progenitor and stem cells: progress and problems. AB - Gene transfer to hematopoietic cells for the purpose of "gene therapy" is a new and rapidly developing field with clinical trials in progress. A fundamental goal of research in this field is the incorporation of exogenous genes into the chromosomes of the most primitive hematopoietic progenitor cells--stem cells. Recombinantly engineered retroviral vectors are the best characterized and are currently the only vector type in clinical trials directed at the hematopoietic system. High efficiency gene transfer and expression in murine stem cells and their progeny is now routine, but in larger animal models such as dogs or primates and preliminary clinical trials, gene transfer has been less successful. Problems such as retroviral efficiency, gene expression, insertional mutagenesis and helper virus contamination are being addressed. A promising new vector, the adeno-associated virus (AAV), has shown promise and may allow production of high titer, stable, recombinant virions without helper contamination and with potentially better safety parameters. However, the technology for AAV gene transfer is currently underdeveloped, and issues related to the reproducible production of vectors must be addressed. Other non-viral vector systems are being explored, but little data are available on applications to hematopoietic cells. Better preclinical models are needed to study gene targeting and expression in human cells. An overview of recombinant retroviral and adeno-associated viral vector production, preclinical data and preliminary clinical data will be given, and problems needing to be addressed at all stages of development before broad clinical utility can be achieved will be discussed. PMID- 7881359 TI - The structure, biology and potential therapeutic applications of recombinant thrombopoietin. AB - Platelets, an integral component of hemostasis, are produced by megakaryocytes derived from the differentiation of pluripotent stem cells in the bone marrow or spleen. After decades of study, the regulation of this process is still not well understood. However, the recent cloning and characterization of thrombopoietin, a ligand for the receptor encoded by the c-mpl proto-oncogene, provides new insights into the humoral regulation of megakaryocytopoiesis and platelet production. Consistent with the proposed role as a major physiological regulator of megakaryocytopoiesis, thrombopoietin has potent effects on megakaryocytopoiesis in vitro and in vivo. In addition to the original supposition that thrombopoietin functions as a late-acting megakaryocyte maturation factor, recombinant thrombopoietin proves also to be a potent stimulator of hematopoietic progenitor cells, inducing them to undergo proliferation and differentiation into megakaryocytic colonies. When administered to mice, thrombopoietin causes an increase in peripheral platelet numbers to previously unattainable levels within a few days. Studies of the efficacy of thrombopoietin are underway. It is envisaged that this new cytokine will have widespread applications as a therapeutic agent for the management of bleeding due to thrombocytopenias, in particular those resulting from cancer chemo- or irradiation therapy. PMID- 7881360 TI - Symposium on aplastic anemia and bone marrow failure. Metropolitan Toronto Convention Center--September 17, 1994. PMID- 7881361 TI - The measurement of blood flow in humans using radioactive tracers. AB - Since the first description of the movement of blood around the body by William Harvey, the accurate measurement of blood velocity has provided a major challenge for medical science. This review looks at the contribution made by techniques using radioactive tracers. Initially consideration is given to the fundamental problem of how to measure the amount of radiotracer in an organ with sufficient accuracy, using both single-photon and positron-emitting tracers. The various models used to link tracer behaviour with blood flow are then discussed and the article closes with a detailed review of the clinical applications of blood flow measurements. PMID- 7881362 TI - The mathematical modelling of thermal responses of normal subjects and burned patients. AB - A model of the human thermoregulatory system has been developed for normal subjects and burned patients treated in the intensive care room at Aberdeen Royal Infirmary. The human body is split into eleven segments, each having core, muscle, fat and skin layers. Heat transport through blood flow and conduction are simulated, and surface heat loss is separated into radiative, convective and evaporative components. Measurement of skin temperature and evaporation of moisture have been made from all sections of the body for 22 normal subjects over a range of environmental temperatures from 20 degrees C to 40 degrees C. The model has been refined to fit the data through manipulation of heat flow commands and temperature set points controlling sweating and shivering. The model has been adapted to describe the responses of burn patients by the introduction of skin layer destruction, increased body metabolism and fluid loss from wounds. Predictions have been compared with measurements made on six patients. The model shows that the ambient temperature at which sweating occurs increases with the area of burn injury, which is confirmed by clinical observations. It has been used to predict optimum environmental temperatures for treatment of patients with burn wounds of varying extent. PMID- 7881363 TI - A variable pitch oxygen saturation indicator designed for use in the magnetic resonance environment. AB - Many commercially available pulse oximeters have a variable pitch blood oxygen saturation indicator, which emits a 'beep' between 175 Hz and 675 Hz with each heart beat. The frequency of this beep is dependent on the blood oxygenation measured by the oximeter, higher frequencies corresponding to higher blood saturation percentages. This is a useful feature for an anaesthetist, rapidly communicating potentially life-threatening situations in an easily detectable manner. Most available oximeters with an audio output feature are vulnerable to the effects of magnetic resonance scanning. In this article an add-on module is described for generating a beep to indicate the blood oxygen saturation which has been specifically designed to operate in the MR environment. PMID- 7881364 TI - An anatomical and physiological model of the renal parenchyma--model development and parametric identification. AB - Renal function is often characterized by the activity/time curves obtained by imaging the aorta and kidney. Non-parametric deconvolution of the activity/time curves is clinically useful as a diagnostic tool in determining renal transit times. Typically non-parametric deconvolution is performed using a technique that does not require a priori information, e.g. matrix-based and Fourier-transform methods. Using data filtering and conservation of mass constraints, non parametric deconvolution continues to exhibit noise in the deconvolved curves. This noise hampers the identification of renal transit times. Given the shortcomings of non-parametric deconvolution, a parametric model of the renal response has been developed. Our model is shown to be anatomically and physiologically plausible. In this paper, the parametric model structure is used, in conjunction with experimental data, to estimate renal physiological parameters. These parameters include the filtration fraction, renal blood transit time and urine transit times. The model parameters are then related to the minimum transit time (MinTT), mean transit time (MTT), glomerular filtration rate (GFR) and parenchymal transit time index (PTTI). As deconvolution techniques often produce negative artifacts, Fine et al developed a technique to determine an aorta background to minimize this effect. In this paper this work is extended to determine a reasonable renal background from aorta activity/time curves. Non parametric deconvolution is used to provide initial estimates of model parameters. The model is then fitted to twelve healthy background-corrected kidneys by an iterative parameter-estimation technique. The normal values correspond to those reported in the literature. These normal values are then used to identify renal arterial stenosis in two renal hypertensive patients. The results suggest that parametric identification, based on a renal-retention function model, may provide additional anatomical and physiological information that is not provided by conventional non-parametric methods. PMID- 7881365 TI - The measurement of steady-state visual evoked cortical potentials using an adaptive noise canceller. AB - A new software method for measuring steady-state visual evoked cortical potentials (VECPs) has been developed using the principle of adaptive noise cancelling. The steady-state VECP is composed of narrow-band frequency components at harmonics of the stimulus frequency. In clinical recordings, these signal components are masked by wide-band noise, predominantly electroencephalographic activity and muscle noise. The stimulus frequency is exactly known and by using a reference sinusoid at the stimulus frequency (or its harmonics) the adaptive noise canceller (ANC) is able to cancel uncorrelated noise components from the recording. In effect, the ANC functions as an adaptive narrow-band-pass filter at the reference frequency. The performance of the ANC has been evaluated using both simulated and physiological signals. The output of the ANC provides temporal information on the signal amplitude and phase, and can be used to calculate the reliability of signal detection. For this application, the ANC has a number of advantages over the fast Fourier transform: it is a more sensitive detector, it requires fewer calculations, it is less computationally intensive, it requires less memory and it can be implemented in real time. PMID- 7881367 TI - A comparison of electrodes for potential use in paediatric/infant apnoea monitoring. AB - We measured the signal-to-motion-artifact ratio for ten paediatric/infant electrodes for infant apnoea monitoring. Electrodes that have good stability, strong adhesion, low face-to-face impedance, low transthoracic-plus-electrode impedance, large effective area, and large total area are optimal for impedance pneumography. The gel make-up may also affect optimality. PMID- 7881366 TI - Apparent cerebral cytochrome aa3 reduction during cardiopulmonary bypass in hypoxaemic children with congenital heart disease. A critical analysis of in vivo near-infrared spectrophotometric data. AB - The purpose of this analysis was critically to examine the changes of cerebral cytochrome oxidase as detected by near-infrared spectrophotometry (NIRS) during induction of cardiopulmonary bypass (CPB) in fourteen children undergoing open heart surgery. Five children were hypoxaemic (arterial oxygen saturation 49%-84%) before the switch to CPB and nine children were not. In the hypoxaemic children, the total cerebral hemoglobin concentration [tHb] decreased rapidly and markedly, reaching a plateau after 2 min. Surprisingly, cytochrome aa3 concentration in its oxygenated form [CytO2] decreased in parallel while the cerebral haemoglobin oxygenation index [HbO2]-[Hb] increased gradually. In the eight normoxaemic children, changes in the NIRS signals were insignificant. When a standard NIRS algorithm was used, the magnitude of the change in [CytO2] was closely associated with the magnitude of the change in [tHb] (p < 0.0001), the time courses of the [CytO2] and [tHb] signals were parallel in 11 of the 14 children and the error of fit in the NIRS multicomponent analysis increased 10- to 100-fold over system noise. A new NIRS algorithm, using wavelength specific optical pathlengths, did not improve the error of fit but produced smaller estimates of [CytO2] changes, which were unrelated to the [tHb] changes. In our opinion the interesting possibility of monitoring cytochrome oxidation by NIRS requires further validation. PMID- 7881368 TI - Input impedance of radiocephalic arteriovenous fistulae for haemodialysis access: its value in predicting early failure. AB - This study is concerned with an assessment of the quality of the blood vessels used in the construction of radiocephalic arteriovenous fistulae for haemodialysis vascular access in 20 patients. Following non-invasive preoperative assessment of the cephalic vein by means of a colour Doppler scanner, input impedance was determined intraoperatively from blood flow and blood pressure measured about 2 cm downstream of the anastomosis. The patients were re-assessed 1 day and 2, 4, 6 and 12 weeks after surgery, and the diameter and the flow through the fistulae, the location of major branches, and the presence and severity of stenoses in the cephalic veins were determined non-invasively. Five fistulae failed within the 12 weeks period following surgery, mainly due to thrombosis. In a further 3 patients, the fistulae were patent but did not achieve an adequately high blood flow and dilate sufficiently for haemodialysis and were therefore considered to be essentially failed. The impedance moduli from 0 to 10 Hz as well as the average impedance modulus of successful fistulae were significantly lower than those of fistulae that subsequently failed. An attempt was made to locate the presence of reflection sites (i.e. stenoses and branches) from the minima in the impedance modulus spectra. Their locations were compared with those of the reflection sites detected by ultrasound 2 weeks after surgery. However, not all reflection sites detected 2 weeks after surgery were located by the impedance method. It is recommended that both preoperative examination and intraoperative haemodynamic measurements be made to improve the accuracy of the assessment. PMID- 7881369 TI - Physiological characteristics of inferior vena cava pulse waveform during foetal development. AB - Non-invasive measurements of pulsatile diameter changes (pulse waveform) in the foetal inferior vena cava (IVC) during foetal development using an ultrasonic phase-locked echo tracking system with high sampling frequency (3000 Hz) are described. Successful human foetal IVC pulse waveform recording was achieved cross-sectionally in 56 out of 68 (82%) women at 20-23, 24-27, 28-31, 32-35, and 36-39 weeks' gestation. The pulse waveform in the foetal IVC consisted of four waves (A, X, V, and Y waves). An increase in the depth of the X and Y descents was observed during the second trimester. It was considered that this was due to the decrease in placental resistance. A slightly decreased foetal heart rate during the third trimester affected the time for right ventricular diastolic filling. Our findings indicate that the alterations in resistance to right ventricular afterload produced by growth in the placenta and right atrioventricular filling patterns with advancing gestational age are reflected in the foetal IVC pulse waveform. In addition, foetal systemic and placental vascular resistance profoundly influence right atrioventricular filling patterns. It is possible to record the foetal IVC pulse waveform simply, using a quite different ultrasound methodology (phase-locked echo tracking) from that used for normal pulse echo or Doppler measurements. Such studies provide important physiological information about the normal foetus. PMID- 7881370 TI - A measurement of pulmonary blood volume increase during systole in humans. AB - Pulmonary blood volume increase during systole was measured in patients by analysing chest images obtained during ECG gated radionuclide angiography examination. The difference in the total radiation counts between systole and diastole in regions of interest, which included the lungs and the left ventricle, was measured and the relative pulmonary systolic blood volume increase (SBVI)-the ratio between the pulmonary SBVI and the cardiac stroke volume-was calculated. The relative pulmonary SBVI, which is a measure for the compliance of the pulmonary blood vessels, was found to be 0.26-0.85, and the average value was 0.57 +/- 0.15. The relative pulmonary SBVI was inversely correlated with the patient age (r = 0.27, p < 0.05) and with the left ventricular ejection fraction and stroke volume (r = 0.36, p < 0.01) due to decreased arterial compliance for older patients and for increased pulmonary blood volume respectively. The correlation coefficients were not high, indicating that the compliance of the patients is determined mainly by other individual factors. Radionuclide plethysmography enables qualitative assessment of pulmonary arterial compliance. PMID- 7881371 TI - A new bioelectrical impedance method for measurement of the erythrocyte sedimentation rate. AB - A new bioelectrical impedance method was developed to determine the erythrocyte sedimentation rate (ESR) by measuring the settling velocity of red blood cells. A sample of blood was collected in a plastic tube with two electrodes, one positioned above the other. Measurements of electrical resistance were made in the upper region of the blood column. As the red blood cells settled towards the bottom of the container, the resistance decreased continuously. The velocity of settling red blood cells was calculated in 45 samples. The values obtained compared favourably with the ESR determined by the standard Westergren method, giving a correlation coefficient of 0.96 and a standard error estimation of 7.0 mmh-1. We conclude that bioelectrical impedance can be used to measure ESR accurately and that this method has important advantages over existing methods. PMID- 7881372 TI - [Differences in temporal organization of "summer" and "winter" sleep in hibernating mammals]. PMID- 7881373 TI - [Population genetics in Russians: genealogical analysis, gene frequency, and genetic distance]. PMID- 7881374 TI - [Growth and functional activity of the ventral gland and marking behavior of red tailed gerbils (Meriones libycus)]. PMID- 7881375 TI - Outbreak of measles in a religious group--Montreal, Quebec. PMID- 7881376 TI - Outbreak of measles among Christian Science students--Missouri and Illinois, 1994. PMID- 7881377 TI - Contact tracing and follow-up of a case of laryngeal tuberculosis--Alberta. PMID- 7881378 TI - Lead intoxication in a child related to the ingestion of playground paint chips- Quebec. PMID- 7881379 TI - Decreased susceptibility of Neisseria gonorrhoeae to fluoroquinolones--Ontario, 1992-1994. PMID- 7881380 TI - Human T-cell lymphotropic virus, type I (HTLV-I) reported in British Columbia. PMID- 7881381 TI - Differentiation and programmed cell death in Sa-45 tumour treated with bone inducer. AB - The relationship between differentiation and concerted cell death was studied using ultrastructural, histochemical and immunochemical methods in solid rat fibrosarcoma Sa-45 grown in the presence of demineralized bone matrix. The control tumour consisted mostly of undifferentiated cells with few poorly or moderately differentiated cells. In the presence of the inducer, cells with a more differentiated pattern appeared in the surrounding area. The proliferative activity in the presence of the inducer was 3 to 5 times lower but the apoptotic index was higher than in the controls. However, complete differentiation was induced only in stromal cells, whereas the parenchymal cells showed signs of enhanced but incomplete differentiation. The ultrastructural signs of programmed cell death progressed in them faster than the corresponding features of maturation, thus leaving differentiation incomplete. PMID- 7881382 TI - Dystrophin does not influence regular cytoskeletal architecture but is required for contractile performance in smooth muscle aortic cells. AB - Cultured vascular smooth muscle cells express distinct histological phenotypes due to a contractile to synthetic stage transition. In this study, we compared the behaviour of cultured aortic smooth muscle cells from young normal and mdx mice. Morphological, immunobiochemical, immunocytochemical analyses and contraction studies of these cells demonstrated that (i) the cell cytoskeleton in mdx mice is not affected by the absence of dystrophin since proteins such as caldesmon, a-actin, and vinculin are expressed similarly in normal mice, (ii) utrophin (or dystrophin-related protein) overexpression does not compensate for the physiological and functional role of the lacking dystrophin. These data suggested that dystrophin and utrophin cannot substitute one another and may play different or complementary roles within smooth muscle cells. PMID- 7881383 TI - Exogenous catalase introduced in CHO cells by electroporation does not protect against chromosome damage induced by ionizing radiation. AB - The relative importance of hydrogen peroxide generated as a consequence of irradiation with X-rays for the production of chromosomal aberrations has been studied in cultured CHO cells. Catalase introduced into cells by electroporation protected DNA from strand breakage induced by hydrogen peroxide given 4h later, and the yield of chromosome aberrations was also reduced. Nevertheless, when the cells were irradiated after treatment with catalase following a similar protocol and the yield of chromosomal aberrations analyzed at metaphase, no protective effect was observed as compared with cells treated with X-rays alone. These observations seem to support the hypothesis that hydroxyl radicals generated from hydrogen peroxide are not a major factor responsible for chromosome damage induced by ionizing radiation. PMID- 7881384 TI - Effect of hyaluronan on the elastase-type activity of human skin fibroblasts. AB - The influence of hyaluronan (HA) on the expression of human skin fibroblast elastase-type protease (HSFEp) (Homsy et al, 1988) was studied. At confluency of HSF cultures, hyaluronan increased the level of HSFEp in a time and dose dependent fashion. Optimal effect was observed after 48 h of culture and at 2 mg/ml HA concentration; the stimulatory effect of HA could be suppressed by 1 microM cycloheximide. The enhancement of enzyme biosynthesis by HA was dependent on cell proliferation but quasi invariant with HSF passage number (from 7-21). PMID- 7881385 TI - Choline acetyltransferase immunoreactivity in the human vestibular end-organs. AB - Acetylcholine (ACh) is believed to play a major role in the efferent vestibular system in several animal models, however no information regarding the role of ACh in the human efferent vestibular system has been published. Post-embedding immunohistochemistry in a hydrophilic resin was used to investigate the choline acetyltransferase immunoreactivity (ChATi) and acetylcholinesterase (AChE) histochemistry in human vestibular end-organs. ChATi and AChE activity was found in numerous bouton-type terminals at the basal area of the vestibular hair cells. These terminals were found to contact type II vestibular hair cells and the afferent chalices surrounding type I hair cells. This study provides the first evidence that the human efferent vestibular axons and terminals are cholinergic. PMID- 7881386 TI - 4-Hydroxynonenal induces membrane perturbations and inhibition of basal prostacyclin production in endothelial cells, and migration of monocytes. AB - Cultured bovine aortic endothelial cells (BAEC) were incubated for 5 days with 10(-5) 4-hydroxynonenal (HN). HN treated BAEC and controls were either (i) further incubated with 125I-polymyxin B (IPxB) or with radioiodinated, inactivated coagulation factor Xa (IFXai) as markers of membrane phospholipid perturbation, or (ii) assayed for the synthesis of prostacyclin (PGI2) and thromboxane A2 (TXA2). Rabbit blood mononuclear cells enriched in monocytes (MC) were isolated and assayed for chemotactic response to HN. The results showed six fold increases of IPxB and IFXai binding to BAEC treated with HN, as compared to untreated controls. We also found in HN treated cells a marked inhibition of PGI2 synthesis, but an unmodified TXA2 production. In addition, HN in the 10(-5)-10( 10) M range induced oriented migration of MC. PMID- 7881388 TI - Setting a prime example. PMID- 7881387 TI - A time to die: ethics of prolonging life. PMID- 7881389 TI - Positive images of ageing. PMID- 7881390 TI - Linking care to excellence. PMID- 7881391 TI - Healing power of touch. PMID- 7881392 TI - Acute confusional states. PMID- 7881393 TI - Basic principles of lifting. PMID- 7881394 TI - Research on eating routines. PMID- 7881395 TI - The value of age. PMID- 7881397 TI - As I was saying.... PMID- 7881396 TI - Innovations in FOCUS. PMID- 7881398 TI - Ringing in care rationing in '95. PMID- 7881399 TI - Medullary-induced alterations in intracranial self-stimulation from the substantia nigra. AB - The intracranial electrical self-stimulation (ICSS) from the substantia nigra (SN) was reduced by simultaneous stimulation of the nucleus of the solitary tract (NTS) in cats. This effect varied with the current intensity and the sequence of NTS stimulation paired with the rewarding SN stimulation. Namely, NTS stimulation preceding the SN stimulation was more effective in lessening ICSS than that following the SN stimulation. Both SN and NTS stimulations produced significant cardiorespiratory effects, when they were applied separately. However, the cardiorespiratory responses to NTS stimulation have no substantial role in altering ICSS, because vagotomy abolished the heart rate effects of NTS stimulation but caused no change in its reducing effect on ICSS. Moreover, no statistically significant correlation was found between the blood pressure changes and the decrease in response rate. These data are interpreted as suggesting that the NTS stimulation may reduce centrally the rewarding value ordinarily derived from ICSS at the SN. PMID- 7881400 TI - Pronounced increase in prolyl endopeptidase activity in primary cultures of rat cerebral cortex during neuronal differentiation. AB - The activity of prolyl endopeptidase (PEP), a cytosolic serine protease, was examined in developing primary cultures of the rat cerebral cortex between days 1 and 16, in vitro. Cells underwent remarkable differentiation during the first week in culture, as indicated by the formation of clusters and by the rapid development and fasciculation of neurites. The specific activity of PEP showed a rapid, about 5-fold increase by day 7. The morphology of cultures remained nearly unchanged and the activity of PEP slightly increased during the second week. Excitotoxic lesion of the neuronal component of mature cultures revealed that the majority (over 70%) of PEP activity is localised in glutamate-sensitive neurons. Our findings indicate that PEP may play some role during neuronal differentiation. PMID- 7881401 TI - Neuronal damage following transient cerebral ischemia and its restoration by neural transplant. AB - The middle cerebral artery (mca) was intraluminally occluded for one hour prior to reperfusion in the rat. Neuronal damage as well as motor imbalance were assessed in both acute and chronic stages with or without neural transplant in the striatum. In acute stage, argyrophil III staining demonstrated "collapsed" dark neurons in the ipsilateral striatum, cortex, reticular thalamus, amygdala and sometimes in the hippocampus. They had shrunken somata and corkscrew-like dendrites. In accordance with the appearance of dark neurons, the immunoreactivity for calpain of endogenous inactive form decreased or disappeared in ischemic areas. In chronic stage, ischemic core area (striatum and cortex) got into porencephaly, and animals made rotations following methamphetamine injection. Neural transplant (fetal striatal cells) was made during 2 to 4 weeks after the ischemia. Once the transplant survived and grew in the striatum, the methamphetamine rotations were attenuated. Using mca ischemic model rats we report here pathophysiological processes that lead to neuronal damage and infarct. Neural transplants into these animals brought partial restoration in motor disturbance, offering a valuable information concerning therapeutic possibility. PMID- 7881402 TI - Identified retinal axons occupy postsynaptic positions in the optic tectum of Bufo marinus. AB - Horseradish peroxidase was applied to the proximal stump of the cut optic nerve, and the anterogradely transported tracer was visualised by the cobalt-intensified diaminobenzidine method. The optic fibre receiving laminae of the optic tectum were systematically searched for those synapses in which the tracer-filled profiles occupied postsynaptic positions. Optic terminals were rarely but regularly postsynaptic to unlabelled, small clear vesicle-containing profiles, mostly in lamina A. Quantitative analysis showed that only in 0.95% of the synapses formed by optic fibres could this arrangement be substantiated. These results suggest that presynaptic modulatory mechanisms may play a role in optic information processing. PMID- 7881403 TI - An immediate morphopathologic response of a subpopulation of astrocytes to electroshock: "dark" astrocytes. AB - Varying numbers of astrocytes lining the subarachnoid and Virchow-Robin's spaces become stainable by a special silver method in brain sections of rats subjected to a single electroshock of "suitable" parameters immediately before being sacrificed by perfusion fixation. This type of argyrophilia is considered to be induced by some electrically caused morphological damage, since the affected astrocytes are dramatically shrunken and hyperchromatic at both light- and electron-microscopic levels. Based on several points of morphopathologic similarity between the electroshock-damaged astrocytes and "dark" cells of various tissues, especially electroshock-induced "dark" neurons, it is supposed that their nature is also similar ("dark" astrocytes). PMID- 7881404 TI - The impairment of long-term potentiation in rats with medial septal lesion and its restoration by cognition enhancers. AB - The effect of medial septal lesion on long-term potentiation (LTP) and the action of four cognition enhancers were studied in rat dentate gyrus, in vivo. The medial septum was partially lesioned by a radiofrequency lesion generator. The effect of lesion was studied on hippocampal function measuring two parameters; the amplitude of the maximal population spikes and the increase in population spikes evoked by high frequency stimulation of the perforant path (LTP). Both parameters were found to be significantly lower in the lesioned group than in the non-lesioned one. Four drugs (physostigmine, piracetam, vinpocetine and Hydergine), known to be effective in dementia and/or in cognitive impairments, were administered 1 h after the lesion procedure and thereafter once a day for 6 days after the operation. LTP was induced and measured at day 7. All drugs produced a complete restoration of the measured parameters affected by the lesion. These findings provided further evidence that the medial septum plays an important role in the induction of LTP in the dentate gyrus. This experimental model might be useful for studying new drugs against dementia. PMID- 7881406 TI - DNA haplotype analysis of Huntington disease reveals clues to the origins and mechanisms of CAG expansion and reasons for geographic variations of prevalence. AB - This study of allelic association using three intra- and two extragenic markers within 150 kb of the Huntington disease (HD) mutation has provided evidence for linkage disequilibrium for four of five markers. Haplotype analysis of 67 HD families using markers in strong linkage disequilibrium with HD identified two haplotypes underlying 77.6% of HD chromosomes. Normal chromosomes with these two haplotypes had a mean number of CAG repeats significantly larger than and an altered distribution of CAG repeats compared with other normal chromosomes. Furthermore, haplotype analysis of five new mutation families reveals that HD has arisen on these same two chromosomal haplotypes. These findings suggest that HD arises more frequently on chromosomes with specific DNA haplotypes and higher CAG repeat lengths. We then studied CAG and CCG repeat lengths in the HD gene on 896 control chromosomes from different ancestries to determine whether the markedly reduced frequency of HD in Finland, Japan, China and African Blacks is associated with an altered frequency of DNA haplotypes and subsequently lower CAG lengths on control chromosomes compared to populations of Western European descent. The results show a highly significant inverse relationship between CAG and CCG repeat lengths. In populations with lowered prevalence rates of HD, CAG repeat lengths are smaller and the distribution of CCG alleles is markedly different from Western European populations. These findings suggest that, in addition to European emigration, new mutations make a contribution to geographical variation of prevalence rates and is consistent with a multistep model of HD developing from normal chromosomes with higher CAG repeat lengths. PMID- 7881405 TI - Abnormal methylation pattern in constitutive and facultative (X inactive chromosome) heterochromatin of ICF patients. AB - We have investigated the distribution of DNA methylation in chromosomes and nuclei of normal individuals and ICF (Immunodeficiency, Centromeric instability and Facial abnormalities) syndrome patients, using 5-methylcytosine monoclonal antibody. In this syndrome, DNA digestion with methyl-sensitive enzymes has previously shown a specific hypomethylation of classical satellites located in constitutive heterochromatin. The chromosome methylation pattern confirms this hypomethylation showing in addition a clear undermethylation of facultative heterochromatin (X inactive chromosome). Antibodies give, in normal and ICF chromosomes, a non-uniform labeling of euchromatin, generating a weak R-like banding pattern on chromosomes. This pattern reflects an unequal distribution of DNA methylation over the genome disclosing another aspect of chromosome organization. The breakpoints of chromosome rearrangements and the heterochromatin stretchings observed in ICF patients were analyzed by means of in situ hybridization. These chromosome modifications involve hypomethylated classical DNA satellite sequences. The underlying hypomethylation, associated with an abnormal chromatin organization, may predispose to chromosome instability. PMID- 7881407 TI - The cloning of FRAXF: trinucleotide repeat expansion and methylation at a third fragile site in distal Xqter. AB - Three fragile sites, FRAXA, FRAXE and FRAXF lie in the Xq27-28 region of the human X chromosome. The expression of FRAXA is associated with the fragile X syndrome, the most prevalent form of inherited mental retardation whilst the expression of FRAXE is associated with a rarer and comparatively milder form of mental handicap. Both the FRAXA and FRAXE sites have been cloned and the fragile site expression found to be due to the expansion of analogous CGG/GCC trinucleotide repeat arrays. We describe here the cloning of the third fragile site, FRAXF, and demonstrate that it involves the expansion of a (GCCGTC)n(GCC)n compound array. PCR analyses across the repeat of normal individuals show that the number of triplets in the array ranges from 12-26 and the most common allele consists of 14 triplet units. Sequencing analyses show that 95% of normal individuals have three copies of the GCCGTC motif and in these individuals, the size variation observed by PCR is due to copy number alterations in the GCC array. In a cytogenetically positive male with developmental delay, the array is expanded by > 900 triplets and the adjacent CpG-rich region is methylated. The array is also expanded in cytogenetically positive carrier females from the family originally used to define the FRAXF site. We conclude that the expanded array corresponds to the FRAXF fragile site. PMID- 7881408 TI - Physical linkage of the fragile site FRA11B and a Jacobsen syndrome chromosome deletion breakpoint in 11q23.3. AB - Autosomal fragile sites, unlike their X-linked counterparts, are not known to be associated with disease. However, one case report has highlighted a possible relationship between the inheritance of a rare folate-sensitive fragile site in band 11q23.3 (FRA11B) and the chromosome 11q23-->qter deletion in Jacobsen (11q-) syndrome. The mother and brother of the reported Jacobsen syndrome child are FRA11B carriers, suggesting that in vivo breakage at the fragile site during early development could have given rise to the chromosome deletion. We have tested this hypothesis by high resolution physical mapping of FRA11B and of the deletion chromosome breakpoint in the Jacobsen syndrome patient. A detailed restriction map of 600 kb of human chromosome band 11q23.3 has been assembled which covers the PBGD, CBL2 and THY1 genes. FISH experiments with YACs and cosmids from this region have localised FRA11B to an interval of approximately 100 kb containing the 5' end of the CBL2 gene, which includes a CCG trinucleotide repeat. This class of repeat is expanded in the four cloned examples of fragile site and therefore the CBL2 repeat is a candidate for the location of FRA11B. Further, it is shown that the chromosomal deletion breakpoint of the Jacobsen syndrome child maps within the same interval as the fragile site. The breakpoint has apparently been repaired and stabilised by the de novo addition of a telomere. These data are consistent with a role for an inherited fragile site in the aetiology of a chromosome deletion syndrome. PMID- 7881409 TI - A multimegabase cluster of snRNA and tRNA genes on chromosome 1p36 harbours an adenovirus/SV40 hybrid virus integration site. AB - Adenovirus type 12 (Ad12) induces gaps at chromosomal bands 1p36, 1q21, 1q42-43 and 17q21 after infection of human embryonic kidney cells. Three of these bands harbour small nuclear RNA genes or pseudogenes, but the study of a possible relationship has been hampered by the lytic character of adenovirus infection. A non-lytic Ad5/SV40 hybrid virus preferentially integrates at 1p36 and the integration site has been cloned. Chromosomal band 1p36 encodes genes for small nuclear RNA U1 (RNU-1) and for the tRNAs of glutamic acid (TRE) and asparagine (TRN). Each of these genes is encoded by 15-30 copies. We studied the organization of these genes and of the viral integration site by pulsed field gel electrophoresis (PFGE) and analysis of yeast artificial chromosomes (YACs). We show that RNU-1, TRE and TRN genes are scattered over a region of probably more than 2 Mb with intergenic distances of up to 125 kb. The Ad5/SV40 integration site maps to identical chromosomal NotI fragments as RNU-1 and TRE. Fine mapping of a YAC shows that the integration site is within 40-70 kb of genes for RNU-1, TRN and TRE. PMID- 7881410 TI - A YAC clone map spanning 7.5 megabases of human chromosome band Xq28. AB - Xq28 has been of special interest in human genetics because a large number of diseases map to this region. As a step in the molecular analysis of the as yet uncloned disease genes, and as a test for the detailed analysis of larger regions of the genome, we have constructed YAC clone contigs covering the 7.5 Mb region between IDS to the telomere on the long arm of the human X chromosome. Contigs were assembled and verified by an integrated hybridization-based strategy. Data was combined from the physical map, from YAC and cosmid mapping experiments, and from the localization of specific transcripts in the region. Two gaps in the YAC map of 250 and 100 kb were covered in part by the aid of cosmid clones, but small gaps of 50 kb each remain. The cloned region is expected to contain yet unidentified genes for at least ten genetic diseases. The construction of ordered YAC clone contigs of Xq28 represents an important step in the molecular identification of these genes, and the further analysis of one of the genetically most interesting regions of the human genome. PMID- 7881411 TI - Disruption of a binding site for hepatocyte nuclear factor 1 in the protein C gene promoter is associated with hereditary thrombophilia. AB - A heterozygous T-->C transition was detected in the putative promoter region of the protein C (PROC) gene in a patient with type I protein C deficiency and a history of recurrent venous thrombosis. This mutation occurred 14 bp upstream of the transcription initiation site and within a sequence strongly homologous to the consensus binding site for the liver-enriched transcription factor, hepatocyte nuclear factor 1 (HNF-1). Transfection experiments demonstrated that a CAT reporter gene construct containing 626 bp of the putative PROC gene promoter was capable of driving CAT expression in HepG2 hepatoma cells. Levels of CAT expression from constructs bearing the mutation were found to be drastically reduced by comparison with the wild-type, consistent with the reduced plasma protein C antigen levels observed in the patient. Gel retardation and cotransfection experiments demonstrated that the mutation abolished both the binding and the transactivating ability of HNF-1 observed with the wild-type PROC gene promoter. Further, the ability of the mutation to disrupt HNF-1 binding appears to be a function not only of the nature of the nucleotide substitution and its position within the recognition sequence, but also of the relative affinity of the wild-type binding site for HNF-1. This analysis is therefore indicative of a vital role for HNF-1 in the expression of the PROC gene in vivo. Taken together with the identification of a human hepatoma cell line which contains HNF-1 but which does not express protein C, these findings are consistent with the view that HNF-1 is necessary although not sufficient for PROC gene expression in the liver. PMID- 7881412 TI - Linkage of Pfeiffer syndrome to chromosome 8 centromere and evidence for genetic heterogeneity. AB - Pfeiffer syndrome (PS) is an autosomal dominant disorder characterized by craniosynostosis, midfacial hypoplasia, and broad thumbs and great toes. We examined 129 individuals from 11 families with PS and performed linkage studies using microsatellite markers spanning the entire genome. Strongest support for linkage was with DNA markers (D8S255, GATA8G08) from chromosome 8. Obligate crossovers exclude close linkage to this region in six families, and there was significant evidence for genetic heterogeneity. A multipoint lod score of 7.15 was obtained in five families. The 11 cM interval between D8S278 and D8S285 contains one gene for PS and also spans the centromere of chromosome 8. PMID- 7881413 TI - Construction of human Y-chromosomal haplotypes using a new polymorphic A to G transition. AB - We report the discovery of a polymorphic A to G transition found on the human Y chromosome by sequencing Y-specific sequence-tagged sites (STSs). It shows maximal linkage disequilibrium with a previously described Alu insertional polymorphism. We analyze further an apparently African Y chromosome which seems to have entered a Mexican Mayan population several generations ago. Using the newly discovered transition and the Y-specific polymorphic Alu insertion, we discuss how the chromosome's haplotype information might be used to answer questions of human origins and migrations. PMID- 7881414 TI - Diverse phenotypes associated with exon 10 mutations of the RET proto-oncogene. AB - Mutations of the RET proto-oncogene are the underlying cause of some cases of Hirschsprung disease (HSCR) and the inherited cancer syndromes multiple endocrine neoplasia types 2A (MEN 2A) and 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). In HSCR these mutations are dispersed throughout the gene, while in MEN 2A and FMTC, they are tightly clustered in five cysteine codons of the RET extracellular domain. HSCR and MEN 2 are usually distinct but occasional families have been reported with both diseases. In each of five families with HSCR with or without MEN 2A or FMTC, we have identified a nucleotide substitution in one of the five cysteine codons previously associated with MEN 2A or FMTC. In one family, which had HSCR as its only phenotype, we detected a Cys-->Trp mutation at codon 609 which had not been previously observed. In three families, both HSCR and MEN 2A were associated with a single Cys-->Arg mutation at either codon 618 or 620 of RET. In the fifth family, FMTC and HSCR were present but we could not determine whether HSCR arose from mutation of the RET locus. We suggest that specific mutations in cysteine codons 618 and 620 result in MEN 2A or FMTC, but can also predispose to HSCR with low penetrance. PMID- 7881415 TI - Somatic mutations of the von Hippel-Lindau disease tumour suppressor gene in non familial clear cell renal carcinoma. AB - Loss of heterozygosity (LOH) studies have suggested that somatic mutations of a tumour suppressor gene or genes on chromosome 3p are a critical event in the pathogenesis of non-familial renal cell carcinoma (RCC). Germline mutations of the von Hippel-Lindau (VHL) disease gene predispose to early onset and multifocal clear cell renal cell carcinoma, and the mechanism of tumorigenesis in VHL disease is consistent with a one-hit mutation model. To investigate the role of somatic VHL gene mutations in non-familial RCC, we analysed 99 primary RCC for VHL gene mutations by SSCP and heteroduplex analysis. Somatic VHL gene mutations were identified in 30 of 65 (46%) sporadic RCC with chromosome 3p allele loss and one of 34 (3%) tumours with no LOH for chromosome 3p. The VHL gene mutations were heterogeneous (17 frameshift deletions, eight missense mutations, four frameshift insertions, one nonsense and one splice site mutation), but no mutations were detected in the first 120 codons of cloned coding sequence. Most RCCs with somatic VHL mutations (23 of 27 (85%) informative cases) had chromosome 3p25 allele loss in the region of the VHL gene so that both alleles of the VHL gene had been inactivated as expected from a two-hit model of tumorigenesis. Detailed histopathology was available for 59 of the tumours investigated: 18 of 43 (42%) RCC with a clear cell appearance had a somatic VHL gene mutation but none of 16 non-clear cell RCC (eight chromophilic, three chromophobe and five oncocytoma) (chi2 = 7.77, P < 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881416 TI - Evidence for recessive as well as dominant forms of startle disease (hyperekplexia) caused by mutations in the alpha 1 subunit of the inhibitory glycine receptor. AB - Startle disease, or hyperekplexia, is characterized by an exaggerated startle reflex and neonatal hypertonia. An autosomal dominant form of the disorder is associated with mutations in the same codon of the alpha 1 subunit of the inhibitory glycine receptor (GLRA 1) resulting in the substitution of an uncharged amino acid for Arg271 in the mature protein. However, recessive transmission is seen in the mouse mutant spasmodic which resembles startle disease phenotypically and is also associated with mutations in Glra 1. We have confirmed the finding of Arg271 mutations in individuals with startle disease in a UK family showing autosomal dominant transmission. In addition we describe an apparently sporadic case, the offspring of a consanguineous mating, who is homozygous for a novel mutation (T1112A) in GLRA 1, which results in the substitution of asparagine for isoleucine at position 244 of the mature protein. This suggests that human startle disease can display recessive as well as dominant inheritance resulting from different mutations in GLRA 1. PMID- 7881417 TI - The substitution of Arg for Gly2433 in the human skeletal muscle ryanodine receptor is associated with malignant hyperthermia. AB - Single strand conformational polymorphism analysis was used to screen exons 43 and 44 in the skeletal muscle ryanodine receptor gene from 17 positively diagnosed members of families in which chromosome 19-linked malignant hyperthermia (MH) was segregating. A polymorphism in two unrelated individuals was found to result from the substitution of A for G7297, leading to the substitution of Arg for Gly2433. This mutation is adjacent to a mutation (Arg2434 to His) previously linked to MH and central core disease (Y. Zhang et al., Nature Genet. 1993, 5, 46-50). Subsequent screening showed the presence of the mutation in four of 106 MH families tested and its absence from about 1000 other chromosomes. The mutation was present in all six individuals in four families who had had an MH reaction, in two obligate carriers and in 10 individuals diagnosed as MH susceptible by the caffeine/halothane contracture test (CHCT). The mutation was present in an individual with a normal response to the CHCT and was absent in three individuals with a positive CHCT response. These discrepancies would be consistent with inaccuracies in the CHCT and/or with segregation of a second MH allele within two of the four affected families. PMID- 7881418 TI - Spectrum of small length germline mutations in the RB1 gene. AB - A screening method based on multiplexed automated fragment length analysis of polymerase chain reaction products was used to identify germline mutations in the RB1 gene. By screening 106 unrelated patients with hereditary retinoblastoma, 20 small deletions (1-18 bp) and seven insertions (1-5 bp) were identified. When collating our data with reported mutations, recurrence of small length mutations was observed at nine sites within the RB1 gene. Most of these contained monotonic runs or direct repeats embedded in homocopolymer tracts. While the majority of mutations resulted in premature truncation, two mutations caused an in-frame loss of F755 and G540 to E545, respectively. A genotype-phenotype comparison of patients carrying different small length mutations did not reveal any consistent relation. Particularly, the two patients with in-frame mutations showed a high number of tumours consistent with regular-penetrance retinoblastoma. PMID- 7881419 TI - Genetic heterogeneity in familial malignant melanoma. AB - Following reports of linkage to chromosome 9p in families with malignant melanoma, we have been studying a series of UK families. Six families were selected with three or more cases of malignant melanoma. We have used a total of twelve markers mapping in the interval 9p13-p23 and constructed a set of haplotypes to study the inheritance of the disease chromosome. Of the six families, three were consistent with linkage to the short arm of 9, although their limited size precluded confirmation of linkage. One family was clearly unlinked, one family was either unlinked, or contains a sporadic case, or delimits the location of the melanoma gene, and one family was essentially uninformative. This is strong evidence for genetic heterogeneity in families with the malignant melanoma phenotype. We have also sequenced exon 2 of the recently identified candidate tumour suppressor gene, p16, in six individuals and found no evidence for germline mutations in this region of the p16 gene in our families with inherited malignant melanoma. PMID- 7881420 TI - Severe (type III) osteogenesis imperfecta due to glycine substitutions in the central domain of the collagen triple helix. AB - The molecular defects responsible for three cases of severe (type III) osteogenesis imperfecta (OI) were investigated. The mutation sites were localized in pro alpha 1(I) and pro alpha 2(I) mRNA molecules, respectively, by chemical cleavage of mismatch in heteroduplex nucleic acids. Mutation identification was achieved by reverse transcription-polymerase chain reaction-DNA amplification, followed by cloning and sequencing. Two unrelated patients were demonstrated to bear the same G-A transition at nucleotide 2418 of the pro alpha 1(I) coding region, leading to G589S substitution and resulting in very similar clinical manifestations. In the latter patient, a G-T transversion at nucleotide 2166 was found in one pro alpha 2(I) allele, which caused a G586V substitution and again severe OI. Presumably all three mutations occurred de novo in the probands, since they were not found in their parents' DNA. The biochemical findings on type I collagen were very similar in all the probands: the mutations here described had little destabilizing effects on triple helix formation, secretion and stability. The half-life of the collagen incorporated into the insoluble matrix was comparable with that of controls. These mutations are localized in the gap zone of the fibrils where mineral nucleation occurs. This fact suggests that they probably do not exert destabilizing effects on the individual collagen molecules, but rather on the mineralization process, once the defective molecules are incorporated into the fibrils, hence causing severe phenotypes. PMID- 7881421 TI - Human dopamine D4 receptor gene: frequent occurrence of a null allele and observation of homozygosity. AB - We report a null mutation in the first exon of the human dopamine D4 receptor (DRD4) gene. The mutation is predicted to result in a truncated non-functional protein and is the first natural nonsense mutation found in a human dopamine receptor gene. It occurs with a frequency of about 2% in the general population. The distribution of the mutation was found to be similar in healthy controls and patients suffering from psychiatric diseases which included schizophrenia, bipolar affective disorder and Tourette's syndrome, indicating that heterozygosity for this mutation in the DRD4 gene is not causally related to major psychiatric diseases. We also identified an adult male who is homozygous for this mutation. He shows no symptoms of major psychiatric illness, but he displays somatic ailments including acousticous neurinoma, obesity and some disturbances of the autonomic nervous system. Some of these symptoms might be related to the absence of functional DRD4 protein. PMID- 7881422 TI - The effect of a single base pair deletion (delta T525) and a C1634T missense mutation (pro545leu) on the expression of lysosomal alpha-glucosidase in patients with glycogen storage disease type II. AB - Glycogen storage disease type II (GSDII, Pompe's disease) is caused by an autosomal recessive inheritance of lysosomal alpha-glucosidase deficiency. By sequence analysis we have identified the mutations in the lysosomal alpha glucosidase gene (GAA) of two unrelated patients, who have one and two copies, respectively, of the same missense mutation. The milder affected adult patient was found to be homozygous for a C1634T transition resulting in the substitution of pro545 by leu. The more severely affected adolescent patient had this same mutant allele combined with a 1 base pair deletion (delta T525) in the second allele causing premature termination at nucleotide positions 658-660. Both these mutations were introduced in wild-type alpha-glucosidase cDNA and expressed in COS-1 cells to analyse their effect. The delta T525 mutation prohibits the formation of lysosomal alpha-glucosidase completely. The pro545-->leu substitution is compatible with normal synthesis but hampers enzyme maturation and results in a 92% net loss of lysosomal alpha-glucosidase activity. The patient with adult GSDII has, in accordance with the allelic constitution, a 2 fold higher residual activity than the patient with juvenile GSDII. The delta T525 deletion was detected in two other unrelated patients, and also the C1634T transition was encountered in two more Caucasian patients with GSDII. PMID- 7881423 TI - A gene responsible for a dominant form of neurosensory non-syndromic deafness maps to the NSRD1 recessive deafness gene interval. AB - The first localization of a gene responsible for autosomal, neurosensory, recessive deafness recently assigned NSRD1 to the centromeric region of human chromosome 13. We now report on a dominant form of neurosensory deafness found in a family of French origin. The deafness is moderate to severe, has a prelingual onset and affects predominantly the high frequencies. The gene responsible for this form of deafness was found by linkage analysis to map to the same region of chromosome 13 as NSRD1. A multipoint analysis gave a maximum lod score of 4.66 with a most likely location close to locus D13S175. This suggests that different mutations in NSRD1 may cause both dominant and recessive neurosensory deafness. PMID- 7881424 TI - Toward understanding the pathogenic mechanisms in gelsolin-related amyloidosis: in vitro expression reveals an abnormal gelsolin fragment. AB - Gelsolin-related amyloidosis, also called familial amyloidosis, Finnish type (FAF) is an autosomal dominantly inherited disorder characterized by progressive polyneuropathy and corneal lattice dystrophy. All the analyzed patients are found to carry a nucleotide substitution of A or T for G654 in their gelsolin gene, which at the protein level results in the conversion of the 187 amino acid residue, aspartic acid, to asparagine or tyrosine, respectively. In this study, we transfected mammalian mesenchymal COS-1 cells with a derivative of the expression vector pCD-X containing cDNA coding for the wild-type (D187) and mutant forms (N187 and Y187) of plasma gelsolin. Both disease-associated mutant forms of gelsolin were found to be abnormally processed, which led to the secretion of an aberrant 68 kDa gelsolin fragment into the culture media. This fragment most probably represents a carboxy-terminal part of the protein and contains the suggested amyloid-forming sequence. Initial data were also obtained for involvement of a metalloendoprotease in the pathologic processing. This aberrant proteolysis is likely to represent a crucial initiator step in the cascade resulting in amyloid accumulation in patients' tissues. PMID- 7881426 TI - Characterization of a point mutation in aspartylglucosaminidase gene: evidence for a readthrough of a translational stop codon. AB - We have identified a novel aspartylglucosaminuria (AGU) mutation in the second exon of the aspartylglucosaminidase (AGA) gene resulting in a lysosomal storage disease in a Puerto Rican pedigree. This T192-->A transversion causes replacement of Cys64 with a premature translational stop codon and the patients' fibroblasts exhibit dramatically decreased steady-state levels of AGA mRNA. Immunofluorescence analysis and analysis of immunoprecipitated metabolically labelled AGA polypeptides from patient fibroblasts unexpectedly revealed traces of normally sized inactive AGA precursor polypeptide instead of the predicted short polypeptide of 40 amino acids, thus demonstrating readthrough due to suppression of the premature translational stop codon. The translated AGA precursor is not processed further and remains inactive. The Cys64 substitution evidently disturbs the folding of the nascent polypeptide in the endoplasmic reticulum, thus preventing activation by proteolytic cleavage. PMID- 7881425 TI - Aberrant splicing in adult onset glycogen storage disease type II (GSDII): molecular identification of an IVS1 (-13T-->G) mutation in a majority of patients and a novel IVS10 (+1GT-->CT) mutation. AB - Two newly identified splice site mutations (IVS1 -13T-->G and IVS10 +1GT-->CT) were found in a patient with adult onset of the autosomal recessive disorder glycogen storage disease type II (GSDII). The IVS1 -13T-->G transversion in the acceptor splice site was found on one allele in over two thirds of adult onset GSDII patients studied (28/41), but was not seen in 58 normal or 12 infantile onset GSDII chromosomes. Molecular analysis of cDNA from the index patient and four additional, ethnically different, individuals carrying the IVS1 -13T-->G transversion showed splicing out of the first coding exon as well as rare utilization of a cryptic splice site in the exon. An IVS10 +1GT-->CT transversion, unique to the index patient, was detected on the second chromosome. The IVS10 +1GT-->CT results in splicing out of exon 10 including part of the enzyme catalytic site. Additionally, a large deletion encompassing exon 18, previously described in four unrelated patients, was also detected in three unrelated adult GSDII patients, two of whom carried the IVS1 -13T-->G transversion. The frequency of the IVS1 splice site mutation suggests that detection of this mutation could potentially aid in the diagnosis of the phenotypically variable syndrome of adult onset GSDII. The finding that the -13T- >G mutation is a very common mutation in adult onset GSDII patients of varying ethnic and racial backgrounds, suggests that it is either an ancient mutation or confers a selective advantage. Although to our knowledge these are the first splice site mutations to be reported for GSDII, additional splice site mutations are likely and could provide the basis for later onset disease in GSDII. PMID- 7881427 TI - Molecular basis for human erythrocyte AMP deaminase deficiency: screening for the major point mutation and identification of other mutations. PMID- 7881429 TI - Identification of seven rather infrequent and one novel CFTR mutation in the Belgian population. PMID- 7881428 TI - A de novo p53 germline mutation affecting codon 151 in a six year old child with multiple tumors. PMID- 7881430 TI - Identification of a homozygous missense mutation (Arg to Gly) in the critical binding region of the human EC-SOD gene (SOD3) and its association with dramatically increased serum enzyme levels. PMID- 7881431 TI - X-linked hydrocephalus and MASA syndrome present in one family are due to a single missense mutation in exon 28 of the L1CAM gene. PMID- 7881432 TI - Accumulation of multiple mutations in tumour suppressor genes during colorectal tumorigenesis in HNPCC patients. PMID- 7881433 TI - Autosomal dominant amyotrophic lateral sclerosis: a novel mutation in the Cu/Zn superoxide dismutase-1 gene. PMID- 7881434 TI - Dinucleotide repeat polymorphism in the human taurine transporter gene (TAUT). PMID- 7881435 TI - Identification of a polymorphism in exon 11 of the RET protooncogene. PMID- 7881436 TI - A polymorphic dinucleotide repeat in the second intron of HUMCLC. PMID- 7881437 TI - An EcoRI RFLP in human phenol sulfotransferase genes. PMID- 7881438 TI - Dinucleotide repeat polymorphism adjacent to CDKN2. PMID- 7881439 TI - Dinucleotide repeat polymorphism at the PPP1CA locus on 11q13. PMID- 7881440 TI - A polymorphic dinucleotide repeat at the human HLA-F locus. PMID- 7881442 TI - A dinucleotide repeat polymorphism in the MYBPH gene. PMID- 7881441 TI - TaqI polymorphism of the human MXI1 gene. PMID- 7881443 TI - HinfI polymorphism detected by FAEES3 cDNA. PMID- 7881445 TI - DGGE polymorphism in intron 10 of MSH2, the HNPCC gene. PMID- 7881444 TI - Dinucleotide repeat polymorphism at the human biglycan (BGN) locus. PMID- 7881446 TI - Adhalin gene polymorphism. PMID- 7881447 TI - Tri- and tetranucleotide repeat polymorphism in the LIPA gene. PMID- 7881448 TI - Dinucleotide repeat polymorphism at the human TYRP1 locus. PMID- 7881449 TI - Diagnostics for the multivariate linear model analysis of 2 x 2 crossover designs. AB - The multivariate linear model Y = X beta + epsilon is used to analyze data in 2 x 2 crossover designs with either univariate or multivariate response. Diagnostics are performed on estimating the effect of interest formulated as C beta U and on testing the general linear hypothesis C beta U = k. The multivariate Cook's distance is extended to be the influence measure by incorporating the contrast matrix C and the transformation matrix U, and magnitude of F(1)-F, the difference between the F approximation of a multivariate test statistic, is proposed as a measure to detect influential observations for testing the hypothesis C beta U = k. Both measures prove to be very useful because the diagnostics are now associated with estimating and testing effects of interest in the context of the experimental design. PMID- 7881450 TI - A comparison of test procedures for multidose animal carcinogenicity assays under competing risks. AB - Four multidose animal carcinogenicity assay trend test procedures based on the chi-square, Hoel-Walburg, log-rank, and Peto procedures are compared under conditions of competing risks. A total of 42 different risk populations are simulated in which a simulated animal can contract one or more of five different tumor types. The risk populations contain such different risks as incidence of tumor increasing with dose, time of death increasing or decreasing with dose, tumor decreasing time of death without necessarily causing death (nonrepresentativeness), and combinations of the above. Each population is analyzed using each of the four procedures for linear dose-response effect for each tumor separately and for all animals with tumors. Results show the Peto procedure to be the most robust of the four, giving rejection rates near the nominal for all competing risk situations and having the best power to reject when rejection is called for. PMID- 7881451 TI - Statistical considerations for design and analysis of a multiperiod crossover study to compare two treatments for migraine headache. AB - The purpose of this paper is to discuss a long-term, multiperiod crossover study to compare two treatments for migraine headache. Principal attention is given to the analysis of an example in which patients randomly received a treatment sequence with test drug for three migraine headaches and placebo for one. An issue that requires attention for this example is the influence of a carryover effect for test drug that was greater when placebo was the subsequent treatment than when test drug was the subsequent treatment. A way to address this issue without excessive loss of power is to consider tests of "total treatment effects," which are weighted averages across headaches of differences between average response to test drug and average response to placebo. Since these weighted averages are linear combinations of treatment effects and carryover effects, their use requires an argument that carryover effects are at least partly a further form of treatment effects. For the example in this paper, this argument is realistic because the test drug could have provided much better relief to migraine headache than other treatment patients might have previously used. A second purpose of the paper is to present some alternative designs for situations like that represented by the example. The structure of variances for alternative specifications for treatment comparison is provided for models of interest for these designs. PMID- 7881452 TI - Evaluation of alternative statistical models for crossover studies to demonstrate caffeine adjuvancy in the treatment of tension headache. AB - This paper discusses alternative statistical models for the analysis of six crossover studies to determine whether better relief of tension headache occurs from treatment with an analgesic plus caffeine (C) than with the analgesic alone (A) or with placebo (P). Each patient in these crossover studies randomly received a pair of distinct medications in such a way as to treat the first two of four headaches with the initial medication in the pair and to treat the third and fourth headaches with the last medication in the pair. In order to have greater power for the C versus A comparison, three times as many patients were randomly assigned to the A:C and C:A sequence groups as to the A:P, C:P, P:A, and P:C sequence groups. An issue of statistical interest for these crossover studies is the extent to which the possibility of unequal carryover effects of the three medications influences the roles of alternative models for data analysis and the interpretation of results. When carryover effects for all three medications are equal, univariate analysis of variance for the difference scores between the average response for the first two headaches and the average response for the third and fourth headaches for each patient provides nearly the same power for pairwise treatment comparisons as more comprehensive multivariate methods for all four headaches. However, for comparisons concerning carryover effects and for treatment comparisons with adjustment for carryover effects, multivariate methods encompassing all four headaches jointly can provide greater power than univariate analysis for difference scores, particularly when there is low intraclass correlation for responses within the same patient. Another noteworthy role for multivariate methods in situations with potentially unequal carryover effects is their capacity to clarify whether multiple types of carryover effects occur across the second, third, and fourth headaches in the respective sequence groups. Multivariate models with alternative specifications of carryover effects are fit to the data from the six crossover studies to compare C, A, and P by weighted least squares. The role of potential variation among centers is addressed in these analyses by the use of stratified proportional means over centers, means of center means, and means ignoring centers. The primary focus of attention in the respective analyses is the evaluation of treatment comparisons with and without adjustment for potential differences among carryover effects of the treatments.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7881453 TI - Estimation and hypothesis testing of treatment effects in animal reproductive toxicology studies. AB - Healy (1) and Dempster et al. (8) proposed statistical methods to evaluate the treatment effects in animal reproductive toxicology research. Both methods assume homogeneous variance for the dams and the pups, respectively, in all the treatment groups. In this paper, via mixed effect modeling, we propose a method to estimate the treatment effects allowing heterogeneous variances for the dams and the pups, respectively, in different treatment groups. Covariates will also be included in the model. A procedure to test the fixed effects is also discussed. An example from an animal reproductive toxicological study is used to illustrate the procedures. PMID- 7881454 TI - Analysis of multiple-dose bioequivalence studies. AB - In multiple-dose bioequivalence studies, it is possible at steady state to take repeated measurements of pharmacokinetic variables, such as area under the curve (AUC) and the maximum concentration (CMAX) of the blood concentration-time profile, within each period of a crossover design. We develop a bivariate random effects model for such a situation in a 2 x 2 crossover design using the natural log scale for AUC and CMAX that assumes no differential carryover effects and includes components for inter- and intrasubject variability with respect to both formulations. We derive the uniformly minimum variance unbiased estimators, which also happen to be restricted maximum likelihood estimators, and we provide a sample size formula. PMID- 7881455 TI - Two methods of analyses for a complex behavioral experiment. PMID- 7881456 TI - A selective and critical review of neuropsychological deficits and the frontal lobes. AB - Presumptions about the functions of the frontal lobes, and the sensitivity and specificity of certain tests to measure frontal lobe functions, are having a substantial influence on both clinical and research conclusions. In this paper the authors examine the details of the studies that have contributed to these presumptions, and find that the evidence to support these conclusions is weak. A detailed evaluation of the evidence relating to the Wisconsin Card Sorting Test and the Thurstone Word Fluency Test is also presented. Finally, the development of the belief that frontal lobe functions can be specifically measured is reviewed. The authors of this paper conclude that the "bewildering array" of deficits attributed to frontal lesions still seems to prevail. PMID- 7881457 TI - Neuropsychological changes in children with cancer: the treatment of missing data in longitudinal studies. AB - Researchers conducting longitudinal studies with children or adults are inevitably confronted with problems of attrition and missing data. Missing data in longitudinal studies is frequently handled by excluding from analyses those cases for whom data are incomplete. This approach to missing data is not optimal. On the one hand, if data are missing at random, then dropping incomplete cases ignores information collected on those cases that could be used to improve estimates of population parameters (e.g., means, variances, covariances, and growth rates) and improve the power of significance tests of statistical hypotheses. On the other hand, if data are not missing at random, then dropping incomplete cases leads to biased parameter estimates and hypothesis tests that may be internally and externally invalid. This study uses three years of follow up data from a longitudinal investigation of neuropsychological outcomes of cancer in children to demonstrate the problems presented by missing data in repeated measures designs and some solutions. In evaluating potential biasing effects of attrition, the study extends previous research on neuropsychological outcomes in pediatric cancer by inclusion of patients whose disease had relapsed, and by comparison of surviving and nonsurviving patients. Although the data presented have specific relevance to the study of neuropsychological outcome in pediatric cancer, the problems of missing data and the solutions presented are relevant to a wide variety of diseases and conditions of interest to researchers in child and adult neuropsychology. PMID- 7881458 TI - Cognitive function after open-heart surgery: are postoperative neuropsychological deficits caused by cardiopulmonary bypass? AB - Despite the many technological developments in arterial perfusion and cardiac surgical procedures, open-heart surgery is still believed to pose a significant risk for cerebral injury. There are several potential causes of brain damage during open-heart surgery, including prolonged or severe arterial hypotension, as well as emboli emanating from the cardiopulmonary bypass circuit or the operative field. This article reviews the available neuropsychological studies of outcome following cardiac valve replacement and coronary artery bypass grafting. Because both procedures are life-saving operations, the research in this area has been quasi-experimental and fraught with methodological problems. Nonetheless, the findings converge to suggest that cognitive dysfunction occurs after open-heart surgery, and that the deficits are attributable, at least in part, to factors specific to the operation or to the patient being maintained on cardiopulmonary bypass. Preliminary findings suggest that embolization is the primary cause of perioperative deficits in uncomplicated operations. Studies have also consistently found preoperative deficits in this population, suggesting that neuropsychological dysfunction is caused by severe chronic cardiac disease as well as open-heart surgery. PMID- 7881459 TI - Transgene detection during early murine embryonic development after pronuclear microinjection. AB - The polymerase chain reaction (PCR) technique was used to detect a whey acidic protein (WAP) gene and transgene presence in mouse ova cultured to various stages of development after pronuclear microinjection at the one-cell stage. The PCR technique detected an endogenous 442 bp WAP DNA sequence in 78% of one-cell, 88% of two-cell and 94% of four-cell ova, and in 95% of morulae and 97% of blastocysts. The heterologous WAP-human protein C transgene was detected in 88% of one-cell, 88% of two-cell and 44% of four-cell ova, and in 40% of morulae and 29% of blastocysts. For comparison, the integration frequency for transgenic mouse production using the same DNA construct was 22%. After five days of in vitro culture, embryos that were either developmentally arrested or fragmented were tested for the presence of the transgene. The injected construct was detected in 83% of arrested one-cell, 85% of arrested two-cell, and 85% of fragmented ova. In culture, only 28% of zygotes microinjected with DNA developed to the blastocysts stage compared to 74% of noninjected zygotes, while 63% of zygotes developed to the blastocyst stage after injection of buffer alone. Pronuclear injection of the transgene at concentrations of 1.5, 15 and 50 micrograms ml-1 resulted in 28, 11 and 9% development to blastocysts and 29, 86 and 88% transgene detection, respectively. Transgene detection was 85, 96 and 97% in degenerate embryos at the respective doses of DNA. These data show that pronuclear microinjection of the transgene is detrimental to subsequent embryonic development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881460 TI - Ballistic transfection of avian primordial germ cell in ovo. AB - In the fowl the primordial germ cells accumulate in the germinal crescent to the anterior of the two-day embryo. A simple ballistic device has been used to fire tungsten particles (mean diameter 1.5 microns) into this region. By coating these projectiles with vector DNA it is possible to transfect these cells. Hatchlings produced by this technique were raised to sexual maturity and shown to contain the foreign DNA in their sperm. G1 offspring containing this DNA were also produced in roughly 20% of these cockerels. In the majority of cases the vector DNA disappeared from the G1 generation as they matured suggesting that in these cases it had been transmitted episomally. PMID- 7881461 TI - Expression of genomic and cDNA transgenes after co-integration in transgenic mice. AB - In general, genomic transgenes are expressed efficiently in mice, while their cDNA-based transgenes are frequently silent. Clark et al. (1992) have shown that silent cDNA transgenes under the control of the sheep beta-lactoglobulin promoter can be activated after co-injecting them with a genomic sheep beta-lactoglobulin transgene. We have tested the general utility of this concept using mouse whey acidic protein (WAP) transgenes. Here we show that WAP cDNA transgenes are virtually silent in transgenic mice. In contrast, WAP transgenes containing all introns are expressed in approximately 50% of the lines at levels ranging from 1% to more than 100% of the endogenous RNA (McKnight et al., 1992). When a WAP genomic transgene was co-injected with a WAP-cDNA, basal activation of the cDNA was possible. However, the activity of the WAP-cDNA transgene did not exceed 1% of the WAP-genomic transgene. This suggests that a permissive integration site capable of supporting basal level transcription can be established, but further events are required for full activation of the transgene. PMID- 7881462 TI - Frequent deletions and sequence aberrations at the transgene junctions of transgenic mice carrying the papillomavirus regulatory and the SV40 TAg gene sequences. AB - Exogenous DNA microinjected into one-cell mouse zygotes either integrates into the host genome within a short time span, or is rapidly degraded. On integration, a transgene sequence is frequently reiterated. In this report, we describe the enzymatic amplification analysis of transgene junctions of 12 transgenic mice carrying different copy numbers of the same transgene with dissimilar ends. The transgene was composed of the regulatory sequence of the type 18 human papillomavirus linked to the TAg gene of the SV40 virus. Nucleotide sequences of 36 of these junctions were also determined. Deletions were found in 33 (91.7%) of the junctions analysed. At the crossover regions, 55.6% contained short overlapping sequences of one to six nucleotides. Insertions of 2-6 extraneous nucleotides were also found in 8.3% of the transgene junctions. Within a 10 nucleotide sequence on both sides of the transgene junctions, topoisomerase I (topo I) cleavage sites, runs of homogeneous purines or pyrimidiens, alternating purine-pyrimidine tracks and (A-T)-rich sequences were found frequently. Stringent control experiments were also performed to ascertain that the observations made were not artefacts resulting from the polymerase chain reaction. Our data therefore indicate that damage had occurred quite frequently and extensively in our transgene construct. Such transgene damage may also occur to various extents in mice carrying other transgenes. Primary structure of the nucleotide sequences of the injected DNA seems to influence the process of transgene reiteration and aberration. PMID- 7881463 TI - Expression of the Escherichia coli fabA gene encoding beta-hydroxydecanoyl thioester dehydrase and transport to chloroplasts in transgenic tobacco. AB - The fabA gene of Escherichia coli encodes beta-hydroxydecanoyl thioester dehydrase (HDDase), a pivotal enzyme in the biosynthesis of the unsaturated fatty acid cis-vaccenic acid, through the anaerobic pathway. This enzyme is specific to bacterial fatty acid biosynthetic pathways, although other enzymes for fatty acid synthesis are very similar in plants and bacteria. We constructed chimaeric plant expression vectors, pfab21 and pfab22, carrying the fabA gene under the transcriptional control of the cauliflower mosaic virus (CaMV) promoter of 35S RNA. In pfab21, fabA was placed directly under the control of the CaMV 35S promoter; whereas in pfab22, the DNA sequence coding for the chloroplast targeting transit peptide (TP) of the pea ribulose-1,5-bisphosphate carboxylase (RuBisCo) small subunit was fused to the fabA gene in order to allow transport of HDDase to the chloroplast, the organelle responsible for de novo fatty acid biosynthesis in plants. Transgenic plants of Nicotiana tabacum were obtained by Agrobacterium-mediated transformation with pfab21 or pfab22. Expression of fabA transcripts of sizes expected from the chimaeric constructs was shown by RNA blot hybridization. The HDDase protein derived from pfab22 was correctly processed and transported to chloroplasts in transformed plants. The enzymatic activity of HDDase was also detected in chloroplasts isolated from the transformants derived from pfab22 (but not pfab21) and in total leaf protein of all transformants. However, no significant changes were observed in the fatty acid compositions, including cis-vaccenic acid, of leaf chloroplasts and self-fertilized seeds. These results are discussed in relation with the possible structural organization of plant fatty acid synthase. PMID- 7881464 TI - Restricted tissue-specific but correct developmental expression mediated by a short human alpha 1AT promoter fragment in transgenic mice. AB - The tissue-specific and developmental pattern of expression controlled by the proximal promoter (position-348 to +15) derived from the human alpha-1 antitrypsin (h alpha 1AT) gene was studied in transgenic mice. The short promoter segment was linked to the chloramphenicol acetyltransferase (CAT) reporter gene. The transgene showed highly specific expression in the liver and the correct developmental pattern of regulation. Interestingly, this short promoter targets expression to the liver with a greater specificity than that reported for larger alpha 1AT promoter fragments. PMID- 7881465 TI - Apoptosis: therapeutic significance in the treatment of androgen-dependent and androgen-independent prostate cancer. AB - To improve survival in men with metastatic prostatic cancer, a therapeutic modality that can effectively eliminate androgen-independent cancer cells is needed desperately. Combination of such an effective modality with androgen ablation could affect all of the heterogeneous populations within prostate tumors of individual patients, thus optimizing the chances of complete cure. Such a therapeutic approach will probably require two types of agents, one with antiproliferative activity affecting the small number of dividing androgen independent cells and one with the capacity to increase the rate of cell death among the non-proliferating androgen-independent prostatic cancer cells present, i.e. the majority. Androgen-responsive human prostate cancer cells are able to undergo programmed cell death after androgen ablation (even if the cells are not in the proliferative cell cycle). Androgen-independent human prostate cancer cells, however, do not activate this apoptotic pathway of cell death in response to androgen ablation. In contrast, androgen-independent human prostate cancer cells can be induced to undergo apoptosis following such alternative treatment modalities as: (a) non-androgen ablative cytotoxic drugs, such as fluorinated pyrimidines, which result in the "thymine-less state", and (b) ionizing irradiation. The apoptotic effect induced by radiation can be significantly potentiated by post-irradiation treatment of the cells with suramin. In contrast, this radiation induced apoptosis can be substantially inhibited by pretreatment of cells with suramin, probably through suramin's ability to arrest proliferating cells in the GO/Gl phase of the cell cycle. These results suggest that treatment of prostate cancer patients with suramin prior to irradiation is likely to inhibit radiation palliation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881466 TI - Biometric assessment of prostate cancer's metastatic potential. AB - Currently, no protocol exists that can assess the metastatic potential of prostate adenocarcinoma. The reason for this is partly due to the lack of information on cellular changes that result in a tumor cell's becoming metastatic. In this investigation, attempts were made to devise a method that correlated with the metastatic potential of AT-1, Mat-Lu, and Mat-LyLu cell lines of the Dunning R-3327 rat prostatic adenocarcinoma system. To accomplish this, we applied BioQuant biometric parameters, i.e., area, shape factor, and cell motility. AT-1 had a lower shape factor and a greater area as compared with the more highly metastatic Mat-Lu subline. No significant difference in area or shape factor was detected between the AT-1 cell line and the highly metastatic Mat-LyLu line. However, the lowly metastatic AT-1 line had less motility as compared with the Mat-Lu and Mat-LyLu lines. This study revealed that metastatic potential could be partially predicted via area and shape factor and accurately predicted via cell motility. PMID- 7881467 TI - Does radical prostatectomy in the presence of positive pelvic lymph nodes enhance survival? AB - A retrospective review was performed on all patients with stage D1 prostate cancer treated at Duke University Medical Center between 1975 and 1989. A total of 156 patients underwent staging pelvic lymph-node dissection for clinically organ-confined prostate cancer (stage A or B) but were found to have disease metastatic to the pelvic lymph nodes (stage D1). Of this population, 42 patients also underwent radical prostatectomy (group 1), leaving 114 who did not have their prostate removed (group 2). The median cancer-specific survival was 11.2 years for group 1 versus 5.8 years for group 2 (P = 0.005). In patients with one or two positive lymph nodes the median cancer-specific survival was 10.2 years for group 1 versus 5.9 years for group 2 (P = 0.015). There was no difference in survival if three or more lymph nodes were positive. Adjuvant treatment with immediate androgen deprivation and/or postoperative radiation therapy failed to improve the survival experience. The incidence of local problems, including stricture formation, bleeding, or regrowth of cancer requiring dilation or surgical intervention (transurethral prostatectomy) averaged 9.5% in group 1 and 24.6% in group 2. These data show that patients with limited node-positive disease selected for radical prostatectomy experience a survival advantage over those denied such therapy and that this advantage is independent of adjunctive therapy. PMID- 7881468 TI - Study of the electromechanical activity of the urinary bladder. An experimental study. AB - The electromechanical activity of the urinary bladder (UB) was studied in 16 dogs. With the animals under anesthesia, the UB was exposed and four electrodes were sutured serially to its anterior wall. Electric activity simultaneously with vesical pressure was recorded for periods of 30 min daily on 10 days. Triphasic pacesetter potentials (PP) were registered from electrodes 1-4, having identical frequency and regular rhythm by all electrodes and being consistent in the individual dog on all test days. Action potentials (AP) followed PP randomly and were accompanied by vesical pressure increase; they represented vesical contractile waves. Balloon distension of the UB effected increased PP and AP frequency. Annular vesical myotomy led to PP and AP disappearance distal but not proximal to the myotomy, which would suggest that (a) the waves spread caudally and (b) a "pacemaker" exists at the upper part of the UB and triggers the PP. PMID- 7881469 TI - Body mass index and adult female urinary incontinence. AB - The aim of the present investigation was to study the possible role of obesity in the etiology of adult female urinary incontinence (UI). A random population sample of 3,114 women aged 30-59 years were mailed a questionnaire concerning UI and, among other things, body weight and height. The overall rate of response was 85%, and the present analysis comprises 2,589 women who supplied information about their body weight and height. The period prevalence of all UI, stress UI, urge UI, and mixed stress and urge UI was 17%, 15%, 9%, and 7%, respectively. The mean body mass index (BMI) was 22.7 kg/m2. Irrespective of other risk indicators, BMI was positively associated with UI prevalence (OR, 1.07/BMI unit; P < 0.0001). BMI interacted with childbirth in predicting stress UI prevalence, with cystitis in predicting urge UI, and with both in predicting mixed UI. Stress UI proved to be the UI type most closely associated with BMI. PMID- 7881470 TI - Effects of magnesium citrate and phytin on reducing urinary calcium excretion in rats. AB - The aim of this study was to determine and compare the effects of both magnesium citrate and phytin on reducing urinary calcium excretion under high-calcium-diet conditions during single and combined treatments. An animal experiment was carried out over a period of 4 weeks in 35 male rats. Urinary calcium excretion was reduced significantly by magnesium citrate and/or phytin in rats fed on high calcium diets. The hypocalciuric effect of magnesium citrate was more evident than that of phytin. Urinary magnesium excretion was high in all experimental groups. However, the urinary magnesium/calcium ratios showed a consistent increase only in the groups treated with magnesium citrate. Urinary citrate excretion showed a relative increase with the introduction of magnesium citrate plus phytin; however, in both the high-calcium-diet group and the magnesium citrate group this was found to be reduced. Urinary phosphate excretion was slightly higher in the groups treated with phytin. There was no definite difference in urinary oxalate concentration between the groups. No significant change was noted in the serum concentration of calcium, magnesium, or phosphate. PMID- 7881471 TI - Study of the artefacts induced by linear array transvaginal ultrasound scanning in urodynamics. AB - In patients with incontinence problems, endovaginal urodynamic ultrasonography is a technique which easily complements manometric examination by permitting a precise study of peri-urethral soft tissue. Use of a linear array probe under standardised conditions gives, at present, the best results. To validate the technique, it is, however, important to understand the artefacts it provokes. Thirty-four patients underwent urethral profilometry at rest and during effort with and without the ultrasonographic probe. In the patients studied, none of the classical urodynamic parameters were modified. However, in cases of narrow vaginas (distance between the arcuate ligament and the ultrasonographic probe less than 12 mm), a small increase in the maximum urethral closure pressure (5 cm H2O) could be observed. The angle between an intra-urethral cotton swab and the horizontal plane was measured at rest and during maximum coughing effort, both with and without the ultrasonographic probe. A significant reduction of the angle was observed at rest and during effort. However, since linear regression is particularly effective in modelling these two artefacts (R2 = 0.8 and 0.7), they can be considered as constants and are not bothersome in clinical practice. Abdominal ultrasound was used in 10 patients during the introduction of the endovaginal ultrasonographic probe to study its impact on the base of the bladder. A clear increase in the posterior urethro-vesical angle was observed, which was shown to be a function of the degree of probe insertion in the vagina. As this artefact was variable and could not be controlled, this angle should no longer be measured using this technique.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881472 TI - Tulane experience with management of urinary incontinence after placement of an artificial urinary sphincter. AB - Persistent urinary incontinence following placement of an artificial urinary sphincter (AUS) presents a challenging diagnostic problem. This report reviews 30 cases (27 males and 3 females) involving urinary incontinence following AUS placement. The mean age of the patients was 64.4 years (range, 10-79 years). Physical examination demonstrated evidence or suspicion of infection or erosion in 7 patients, and subsequent cystoscopic examination revealed erosion caused by the cuff in 6 of these 7 cases. The remaining 23 patients were evaluated by videofluorourodynamics (VFUD) to ascertain the cause of incontinence. VFUD demonstrated detrusor instability in 9 patients (39%), low detrusor compliance in 3 patients (13%), and poor detrusor contractility in 1 patient (4.4%). Bladder outlet obstruction was diagnosed in 2 patients (8.8%)-1 with bladder-neck contracture and 1 with ureteral stricture. Altogether, 2 (8.8%) cases of tissue atrophy were diagnosed with low urethral closing pressure at the cuff. In all, 1 patient (4.4%) was diagnosed as having a vesicovaginal fistula, 1 (4.4%) had a tubing kink, and 4 (17%) had leaking devices diagnosed during VFUD by cycling of the device. Of the 23 patients, 21 (91%) demonstrably improve or became fully continent after appropriate treatment had been initiated. A review of this study suggests that the majority of incontinent patients after AUS implantation can be managed successfully, provided that a systematic diagnostic approach is followed and appropriate treatment is initiated. PMID- 7881473 TI - Specific binding of bacillus Calmette-Guerin to urothelial tumor cells in vitro. AB - Intravesical immunotherapy with bacillus Calmette-Guerin (BCG) against recurrences of superficial bladder cancer and carcinoma in situ is a highly effective regimen in urology. Despite intensive efforts to clarify the immunological mechanisms of the most successful immunotherapy known today, the cellular mechanism of its antitumor activity remains unknown. In our approach to elucidate the way of action of intravesical BCG, we applied an in vitro adhesion assay to investigate the interaction of radiolabeled BCG with urothelial bladder tumor cells. We demonstrated a BCG dose-dependent binding to bladder-tumor cell lines derived from tumors of different gradings. The binding of BCG is apparently specific, since competition experiments showed an inhibition by nonradioactive BCG but not by Escherichia coli. We also found that there was no difference between the binding of living or heat-killed mycobacteria. Control experiments showed only a low affinity of BCG for fibroblasts, smooth-muscle cells, and endothelial cells in comparison with the tumor cells. Furthermore, we investigated the role of fibronectin as an adhesion molecule that is also present in the bladder wall. We demonstrated that BCG was capable of binding to fibronectin-coated surfaces in a dose-dependent manner. However, competitive binding assays failed to reveal an inhibition of the binding of BCG to bladder tumor cells by anti-fibronectin. Furthermore, binding was not influenced by soluble fibronectin. These data suggest that the in vitro attachment of BCG to bladder-tumor cells appears not to be mediated by fibronectin. In electron microscope studies an adhesion of BCG to bladder-tumor cells was observed after an incubation period of ony 30 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881474 TI - Detection of P53 tumor-suppressor-gene protein in bladder tumors and prostate cancer: possible clinical implications. AB - For a variety of human malignancies such as breast cancer and cancer of the prostate, p53 oncoprotein overexpression indicating an alteration of the p53 tumor-suppressor gene has been described as a prognostic factor for a poor clinical outcome. To investigate the overexpression of p53 oncoprotein in transitional-cell carcinoma of the bladder, 58 bladder cancer specimens of different clinical stages and histological grades were investigated using an immunohistochemical approach. A correlation between p53 positivity and tumor stage was observed, with an increase from 38.5% of superficial (Ta) tumors to 83.3% of muscle-invasive (T3/T4) tumors staining positively for p53 oncoprotein. Furthermore, an increase from 46.7% of G1 tumors to 75% of G3 tumors was observed. In 22 of 25 (87%) informative patients the results of the immunohistochemical staining could be verified by the determination of p53 mutations as detected by polymerase chain reaction (PCR)-directed analysis of restriction-fragment-length polymorphisms (RFLP). To determine the prognostic value of p53 immunohistochemistry for the clinical course of superficial bladder cancer, the overexpression of p53 oncoprotein was investigated in 41 patients with superficial bladder tumors (T1) undergoing complete transurethral tumor resection. The detection of p53 protein was correlated with further clinically important variables such as sex, age, histological grading, former instillation therapy, and immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating-cell nuclear antigen; monoclonal antibody PC10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881475 TI - Isolated necrotizing granulomatous vasculitis of the epididymis and spermatic cords. AB - A 71-year-old man with a painful scrotal swelling was found to have necrotizing granulomatous vasculitis of the epididymis and spermatic cords. No systemic symptom was present, nor was there serological or haematological evidence of systemic vasculitis. PMID- 7881476 TI - Ovarian cancer: screening, treatment, and followup. AB - OBJECTIVE: To provide physicians with a current consensus on screening, prevention, diagnosis, and treatment of ovarian cancer. PARTICIPANTS: A non Federal, nonadvocate, 14-member consensus panel representing the fields of gynecologic, medical, and radiation oncology, obstetrics/gynecology, and biostatistics; 25 experts in obstetrics/gynecology and gynecologic, medical, and radiation oncology who presented data to the consensus panel; and a conference audience of approximately 500. EVIDENCE: The literature was searched through Medline and an extensive bibliography of references was produced for the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given priority over clinical anecdotal experience. CONSENSUS: The panel, answering predefined consensus questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. CONSENSUS STATEMENT: The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. The panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. CONCLUSIONS: There is no evidence available yet that the current screening modalities of CA 125 and transvaginal ultrasonography can be effectively used for widespread screening to reduce mortality from ovarian cancer nor that their use will result in decreased rather than increased morbidity and mortality. Women with stage IA grade 1 and IB grade 1 ovarian cancer do not require postoperative adjuvant therapy. Many remaining stage I patients do require chemotherapy. Subsets of stage I must be fully defined and ideal treatment determined. Women with stages II, III, and IV epithelial ovarian cancer (other than low malignant potential tumors) should receive postoperative chemotherapy. PMID- 7881477 TI - Why get accredited? PMID- 7881478 TI - Keeping consultation alive. PMID- 7881479 TI - Keeping fellow nurses well. PMID- 7881481 TI - A nursing premiere. PMID- 7881480 TI - One health union? A strong, clear voice for the profession. We need the courage to change. PMID- 7881482 TI - Stressed adults and their care. PMID- 7881483 TI - Conditions in common. PMID- 7881484 TI - Helping AIDS sufferers at home. Interview by Teresa O'Connor. PMID- 7881485 TI - A nursing career ends. Interview by Teresa O'Connor. PMID- 7881486 TI - [Estrogens and progestins in replacement therapy in menopause]. PMID- 7881487 TI - [Contribution of ultrasonography in the assessment of the endometrium and the myometrium]. PMID- 7881488 TI - [Pelvic pain and external endometriosis. Physiopathology and treatment]. AB - New data on the pathophysiology of pain associated with endometriosis are available. The predominant role of deep endometriosis has been stressed. In multivariate analysis, superficial endometriosis and even adhesions and ovarian cysts do not appear to be related with pain. Deep endometriosis is usually located posterior to the vagina and cervix, involving the pouch of Douglas, the rectovaginal septum and the uterosacral ligaments. In such cases, pelvic examination shows a painful induration or a nodule in this area. The anterior cul de-sac and the lateral pelvic wall may also be involved. Two histological and clinical aspects may be observed: deep endometriosis arising under the peritoneal surface, or adenomyosis arising from the uterine cervix. Only complete surgical excision may be curative, but recurrences may occur after surgery. Hormonal therapy is only suspensive. However, surgical therapy involves a significant risk of complication. Surgery for deep endometriosis may be one of the most difficult gynecologic operations. It should be performed only by experienced surgeons, with skills in oncological dissections of the pelvis. The guidelines for therapy are thus clear. Superficial endometriosis does not cause pain and should not be treated by itself; symptomatic relief of pain may be obtained by therapeutic amenorrhea or by the placebo effect of surgery. Endometriomas are managed in the same way as all organic ovarian cysts. Adhesions are lysed if infertility is associated with pain, or to gain access to the retroperitoneal area. Etiologic therapy is acceptable only in case of deep endometriosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881489 TI - [Value of controlled hyperstimulation in intrauterine inseminations]. AB - 85 patients, with various forms of infertility but who have at least one patent tube, were treated by superovulation with intra uterine insemination of sperm migrated on a discontinuous Percoll gradient. 231 cycles were carried out. 43 clinical pregnancies were achieved. 26 pregnancies were delivered. The mean cycle fecondity rate was 19% (43/231), 18% in the group of male infertility (13/72), 15% in the group of unexplained infertility (13/88), and 23% in the group of various subfertility factors (17/71). There was 20% of twins nor triplets neither quadruplets. There was no sever hyperstimulation. The role of superovulation, the interest of the technic in male infertility, the risk of hyperstimulation and multiple pregnancies are discussed in the text. PMID- 7881491 TI - [Repeated spontaneous abortions: discussion on its etiologies]. AB - Spontaneous abortion (SA) is the most common complication of pregnancy and is estimated to be between 15 to 20% of all clinical pregnancies. However for "recurrent spontaneous abortion" (RSA) the frequency is more difficult to determine (between 0.05 to 1%). The purpose of this paper is to review the literature concerning RSA etiologies. Particular attention has been paid to the male factors contribution in RSA. Because of the poverty of controlled studies, answers to questions about the RSA are very difficult. PMID- 7881490 TI - [Value of preoperative embolization of uterine fibroma: report of a multicenter series of 31 cases]. AB - Pre-operative embolization of fibroids, an intervention radiology technique, significantly reduces the per and post-operative bleeding. It is an interesting alternative in the looking after of patients who have to undergo multiple myomectomies or the operation of voluminous fibroids responsible of large bleeding. PMID- 7881492 TI - [Voluntary female sterilization: legislation and jurisprudence in France]. AB - Female sterilisation, widely used as a contraceptive technique in France for many decades, is now a cause for concern among clinicians in relation to the personal legal risks involved in such procedures. Questions concerning the position of insurers in relation to application of civil hability insurance in the context of these procedures and their possible complications reinforce this uncertainty. Sterilisation, in the absence of any therapeutic objective, which is at the centre of the current debate, can be considered to be a deliberate mutilation, performed as an illegal procedure and the insurer, on principle, cannot insure the consequences of such an intentionally concomitted act. As described in this paper, the absence of legislation concerning this procedure and the limited legal debate on this subject tend to perpetuate the ambiguity between what is prohibited by law, but largely tolerated in reality. PMID- 7881493 TI - [Risk of ovarian cancer in women treated for infertility]. PMID- 7881494 TI - The demography, phenomenology, and family history of 22 persons with compulsive hair pulling. AB - This study reports on the demographics, phenomenology, and family history of 22 compulsive hair pullers. Subjects were recruited through a psychiatric outpatient clinic as well as newspaper advertisements. Subjects completed a semistructured interview focused on hair-pulling behavior and demographics, the Diagnostic Interview Schedule to assess major (Axis I) mental disorders, and the Structured Interview for DSM-III-R Personality Disorders to assess Axis II disorders. The typical subject was a 33-year-old woman who had completed 1 or more years of college and had been pulling her hair for 19 years. Nearly two-thirds met the criteria for a major mental disorder (particularly anxiety and mood disorders), and more than one-half met the criteria for a personality disorder. Nearly three quarters of first-degree relatives were reported to have a psychiatric disorder, and about 5% were reported to be hair pullers. PMID- 7881495 TI - Bupropion in tricyclic antidepressant nonresponders with unipolar major depressive disorder. AB - Tricyclic antidepressant (TCA) medications are among the most widely used pharmacologic treatments for depression. However, a substantial number of patients fail to respond to these agents. Few standardized trials of pharmacologic treatments for TCA nonresponders are available. Bupropion has an apparently different mechanism of action than TCAs and represents a possible treatment for the TCA nonresponder. Based on positive results from pilot studies, a standardized study evaluating bupropion in TCA nonresponders was conducted. Forty-one depressed outpatients who had failed to respond to adequate documented TCA treatment, defined by specific criteria of dosage, duration, and plasma concentrations, entered a 1-week single-blind placebo phase, followed by an open 8-week bupropion treatment phase utilizing doses of up to the maximum daily dose of 450 mg. Response was measured by change on the Hamilton Depression Rating Scale (HAM-D), Clinical Global Impressions-Severity (CGI-S) and Improvement (CGI I) Scales, and the Hamilton Anxiety Rating Scale (HAM-A). Bupropion treatment resulted in an improvement in depression on all outcome measures. Forty-nine percent were considered "responders," in that they achieved > or = 50% improvement on the 28-item HAM-D. Fifty-four percent were classified as responders based on a CGI-I rating of much or very much improved. Statistically significant improvement in depressive symptoms, measured by mean scores for the HAM-D, CGI-S, and HAM-A, was achieved at the end of the study (as compared to baseline). Twelve patients (32%) had a HAM-D score of < or = 10 at termination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881496 TI - Sleep terror disorder and insomnia treated with trazodone: a case report. AB - A 7-year-old girl who suffered from severe sleep terror disorder was unsuccessfully treated with imipramine, hydroxyzine, and thioridazine. Trazodone at night provided a remarkable relief of the symptoms of her sleep terror disorder. Trazodone might be another alternative in the treatment of this rare disorder. PMID- 7881498 TI - Diagnostic and statistical manual of mental disorders, 3rd ed. (DSM-III), adaptive functioning in young Swedish suicides. AB - Fifty-eight consecutive suicides between 15 and 29 years of age occurring in Goteborg, Sweden, were assessed in accordance with DSM-III Axis V (highest level of adaptive functioning in the past year). The levels of adaptive functioning were compared to principal Axes I and II disorders. Subjects with a borderline personality or schizophrenic disorder as the principal disorder tended to have poor to very poor adaptive functioning and were frequently associated with substance abuse (19 of 24 subjects). Subjects with adjustment disorder or major depressive disorder as the principal disorder generally had very good to fair adaptive functioning. Clinicians are reminded that apparently higher functioning as defined by DSM-III Axis V is no insurance against suicide. PMID- 7881497 TI - Diagnostic and treatment implications of psychiatric comorbidity with migraine. AB - Although an association between migraine and psychiatric disorders has been recognized for over 100 years, this association has been investigated systematically only recently in clinical and community samples. Mechanisms for comorbidity between migraine and psychopathology have also been examined in recent family, pharmacologic treatment, and challenge studies. We review the evidence of an association between migraine and mood, anxiety, and eating disorders and discuss the implications of this association in the diagnosis and pharmacologic treatment of patients with psychiatric disorders and comorbid migraine. PMID- 7881499 TI - Clozapine-associated neutropenic enterocolitis. AB - Clozapine's use has been restricted to the treatment of schizophrenic patients unresponsive to conventional antipsychotics, secondary to its propensity to cause agranulocytosis. Because of this restriction, side effects associated with clozapine's use have probably not been fully elucidated. The authors describe a case of a male schizophrenic who developed clozapine-induced agranulocytosis and subsequently a neutropenic enterocolitis. Neutropenic enterocolitis related to clozapine-induced neutropenia or agranulocytosis has not previously been reported in the literature. The history of clozapine, its side effects, and the phenomenon of neutropenic enterocolitis are briefly reviewed. PMID- 7881500 TI - Sertraline pharmacotherapy for paraphilias and paraphilia-related disorders: an open trial. AB - Twenty-four men with paraphilias (PA; n = 13) and paraphilia-related disorders (PRD; n = 11) were consecutively treated with sertraline (mean dose, 100 mg/day; mean duration, 17.4 +/- 18.6 weeks). Baseline depression severity, total sexual outlet (TSO), and average time per day (ATD) spent in unconventional sexual behavior were obtained. At outcome, sertraline produced a statistically significant reduction in unconventional TSO and ATD in both PAs and PRDs without adversely affecting conventional TSO. This therapeutic effect was independent of baseline depression severity score. Clinically significant improvement was reported by approximately one-half of the men who complied with at least 4 weeks of sertraline pharmacotherapy. Nine men who failed to respond to sertraline were subsequently given fluoxetine. Fluoxetine (mean dose, 50 mg/day; mean duration, 30 weeks) produced a clinically significant effect in 6 additional men. Overall, 17 of the 24 men (70.8%) who received pharmacological treatment with sertraline and/or fluoxetine for at least 4 weeks sustained a clinically significant response, at times lasting more than 1 year. The evolving role of selective serotonin reuptake inhibitors for the amelioration of sexual impulse disorders is discussed. PMID- 7881501 TI - The role of parkinsonism and antiparkinsonian therapy in the subsequent development of tardive dyskinesia. AB - Tardive dyskinesia (TD) is a side effect of prolonged neuroleptic treatment presenting as abnormal involuntary movements. This troublesome disorder occurs in only 15-30% of patients taking neuroleptics, suggesting that these individuals may be physiologically distinct so as to be predisposed. This study analyzed possible factors contributing to TD development. Fifty patients on depot neuroleptics for more than 7.1 years were prospectively examined for TD and drug induced parkinsonism (DIP) using the Smith-Trims rating scale for an average of 5 years. The patients were assessed for the severity of the movement and if the movement increased or decreased with respect to neuroleptic dosage, anticholinergic dosage, parkinsonism, and other related factors. Both TD and DIP increased over time. In the patients whose dose of neuroleptic decreased, the increase in TD ratings was not significant. Using a forward stepwise regression DIP was found to increase as TD worsened but did not appear to predict subsequent TD development. Anticholinergic treatment showed a less significant correlation with the change in TD. These results have implications for the management of combined TD and DIP presentation. PMID- 7881502 TI - Electroconvulsive therapy (ECT) stimulus charge rate and its efficacy. PMID- 7881503 TI - Perceived support and counselling needs in relation to in vitro fertilization. AB - This paper reports findings from a study investigating perceived support and desire for support in a sample of 101 men and 117 women who were consecutive referrals to an in vitro fertilization (IVF) clinic. Both men and women perceived their partners as providing the most support and there were only small gender differences in the extent to which other people were perceived as supportive. There were also only modest gender differences in the types of support participants felt to be desirable and both men and women felt that support would be most desirable after a failed IVF cycle. Both men and women also felt that a routinely provided information booklet about the practical aspects of IVF would improve knowledge of and passage through an IVF cycle. There was a tendency for women who expressed a desire for some form of counselling or support to obtain higher General Health Questionnaire scores. Implications of the results for counselling provision are discussed. PMID- 7881504 TI - Attitudes to body weight, weight gain and eating behavior in pregnancy. AB - The eating behavior and attitudes to body weight of 100 healthy women were studied 3 days after the birth of their first child. During pregnancy women 'watch their weight' and use a range of methods of weight control which include cigarette smoking and inducing vomiting. During pregnancy 41 women reported weight control problems and 20 women considered their weight and eating problems to be greater than at any previous time. Picking was the most common unwanted behavior. Binge eating was experienced by 44 women, nine of whom reported it to be a 'severe' problem. Although women were ambivalent about being weighed at each antenatal visit, 81 recommended weighing once each month. The women held differing opinions on the effects of breastfeeding on body weight and on the need for nutritional supplements during pregnancy. Women reporting 'disordered eating' were more likely to have antenatal complications and give birth to low birthweight babies. The results suggest good obstetric care should include a history of the woman's eating behavior and body weight. PMID- 7881505 TI - Obsessional symptoms in expectant women and outcome of their pregnancy. AB - The aim of this investigation was to explore whether, within the scope of personality traits and their modifications during pregnancy, the obsessional dimension may have a protective role against premature birth. In fact, obsessional characterology with its tendency to control may suggest that the women with these traits do not passively experience their pregnancy and may try to control its evolution, at least in their fantasies. Personality dimensions have been recorded using Derogatis' psychological self-administered questionnaire, in which women were asked to assess their level on the Derogatis symptom scale before and during pregnancy. The survey involved 351 women (117 premature and 234 term deliveries) who had both completed the self-administered questionnaire on the 6-month pregnancy visit and answered a specific interview at birth. Our results have shown that the existence of obsessional traits before pregnancy apparently does not have a protective role against premature delivery (odds ratio = 1.40; NS). Conversely, intensified obsessional symptoms during pregnancy are associated with a decreased premature birth rate (odds ratio = 0.44; p < 0.05). These results remain when the presence of obsessional traits before pregnancy is taken into account (adjusted odds ratio = 0.38; p < 0.02). The possibility of a defence reaction to this situation of pregnancy is discussed. PMID- 7881506 TI - The relationship between maternal relaxation and plasma beta-endorphin levels during parturition. AB - beta-endorphin (beta-EP) levels increase in maternal plasma starting from the 10th to the 12th week of pregnancy and reach a peak during labor and at delivery. Respiratory autogenous training (RAT) has been acclaimed as one of the most effective non-pharmacological methods of obtaining hypoalgesia and relaxing perineal muscles during labor. In order to study the effects of the RAT method in both maternal and fetal beta-EP levels during labor, 28 pregnant women were enrolled in this study. Fourteen attended a RAT program, while the others (control group) did not. beta-EP levels in both groups were measured in maternal plasma at early and late labor, at delivery and on the 4th day of the puerperium and in umbilical cord blood at birth. From late labor on, beta-EP maternal plasma levels increased significantly less in the RAT group than in the control group. The gap in the beta-EP levels between both groups was still significant at puerperium and in umbilical cord blood. In conclusion, the RAT method favorably modulates the secretion of beta-EP during labor and at delivery. This result supports the effectiveness of the RAT method in reducing both maternal and fetal stress during labor. PMID- 7881507 TI - What women say about their birth experiences: a cross-cultural study. AB - The reactions of 221 women to their place of delivery (state or private hospital), type of delivery (vaginal or Caesarean) and associated obstetrical interventions were explored by means of a structured interview conducted at 3 months postpartum. Women were randomly selected from the birth records of three cultural groups residing in the municiple area of Johannesburg, South Africa: White (n = 72), Indian (n = 79) and Mixed cultural origin (n = 78). The type of birth experienced by women differed in the cultural groups examined. While most women experienced positive emotional reactions to birth many also expressed a variety of negative reactions. The differences in care experienced by women in the present study reflect the impact of the two systems of care, private and state, that are available to women in South Africa. PMID- 7881508 TI - Sexuality after hysterectomy: a model based on quantitative and qualitative analysis of 104 women before and after subtotal hysterectomy. AB - To study the effect of subtotal hysterectomy on a woman's sexual life 104 women were interviewed 1 month before and 1 year after subtotal hysterectomy. The interview was semi-structured with the addition of unstructured, open questions. Data concerning sexuality before and after the operation were evaluated with statistical methods, and the result was compared to the answers to the open questions. The most important factor for postoperative sexuality was preoperative sexual activity and enjoyment. Most women described the meaning of sexuality in terms of partner relationship. Those who reported improved sexuality in most cases described the improvement in terms of improved personal sexual capacity, whereas most cases of deterioration described the deterioration in terms of absent, poor, or malfunctioning partner relationship. A model for sexuality after hysterectomy is introduced. Sexual functioning before the operation is the most important factor. Partner sexual functioning, socioemotional support from the partner, adaptation to the consequences of the hysterectomy, mental status, physical ability and hormonal status are other factors influencing sexuality after hysterectomy. PMID- 7881509 TI - Teaching research: the experience of an introductory course for student nurses in Italy. AB - This paper describes the experience of an introductory course in research methodology which was developed at the Nursing School of the Istituto per l'Infanzia of Trieste, Italy. Third-year student nurses were led to understand the basic principles of research through the design and implementation of a real research project, aimed at exploring mothers' views about rooming-in, nursery organization, and the quality of care received during the first days after delivery. A problem-solving approach to research, where methodological choices were presented as 'problems' whose best solution had to be found on the basis of the study objective and of the available resources, small group working under the supervision of a tutor, and oral class presentation of the work performed, represented the major teaching strategies. PMID- 7881510 TI - Foreign gene transfer into nigorobuna (Carassius auratus grandoculis). AB - Supercoiled and linear plasmid DNA containing the Escherichia coli beta galactosidase gene was injected into dechorionated nigorobuna (Carassius auratus grandoculis) eggs prior to first cleavage. The survival rates in the hatching stage were 73% to 89% for injected eggs in comparison with controls (non-injected chorionated eggs). The exogenous DNA was detected by polymerase chain reaction (PCR) in all of the three-day-old larvae analyzed and in about 20% of two-year old adult fish. Expression of the transgene was easily examined by a histochemical method using dechorionated eggs. The incidence of beta galactosidase-positive embryos was highest in the gastrula or embryonic-body formation stage and became low in the embryonic-body-movement stage. These results suggest the usefulness of funa (Carassius fishes) as a model fish in transgenic experiments, and the applicability of the transgenic technique to the improvement of funa as a food source. PMID- 7881511 TI - Bulk isolation and identification of fish genes by cDNA clone tagging. AB - The fish has long been a popular research model for various disciplines in the life sciences, but its molecular biology remains largely unexplored, and the number of fish genes identified at present is still limited. To increase the repertoire of fish genes to facilitate further research, we have embarked on cDNA clone tagging studies in several teleosts. The basic procedure is partial sequencing of randomly selected cDNA clones by a single sequencing reaction to obtain nucleotide sequences of about 200 to 300 bp for each clone. These partial DNA sequences can be used as tags to identify fish homologous genes by searching for sequence similarity in DNA databases. By this method, we have sequenced a total of 265 clones from pituitary and liver cDNA libraries from five species of fish and identified 83 clones encoding 55 different genes. These 55 genes are described for the first time in their species, and 37 of them are described for the first time in fish. These preliminary data indicate that cDNA clone tagging is useful for rapidly increasing the number and availability of genes in teleosts. Several applications of these tagged random clones are discussed. PMID- 7881512 TI - Identification and characterization of metallothionein cDNA from mRNA transcripts induced by starvation in Atlantic cod (Gadus morhua). AB - A cDNA from metallothionein (MT) messenger RNA was identified in a library representing mRNA transcripts that are abundant in starving Atlantic cod larvae. The cod MT cDNA is closely related to MT mRNAs from other fish species and codes for a predicted 60 amino acid peptide. In adult cod liver MT mRNA is abundant and it is detected in cod eggs and larvae. Levels of MT mRNA were four times higher in three-week-old cod larvae starved for six days than in fed larvae, while starvation of four-week-old larvae for eight days resulted in a nearly seven-fold elevation in MT mRNA levels. PMID- 7881513 TI - Adenylate levels and environmental stress in the sea anemone Anthopleura elegantissima. AB - The tissue concentrations of adenosine nucleotides in the sea anemone Anthopleura elegantissima were determined during laboratory manipulations simulating natural environmental stresses: desiccation at low and high air temperatures, increased seawater temperature, mechanical disturbance causing column contraction, and starvation. The levels of adenylates significantly decreased during anemone desiccation, column contraction, and starvation. Variations in adenylate energy charge, the ratio of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and the ratio of ATP to total adenylates were compared with changes in absolute adenylate concentrations to determine the usefulness of these ratios in indicating changes in metabolic activity and physiological stress. The changes in the adenylate levels were far greater than the changes in adenylate ratios. The usefulness of adenylate energy charge, or the other adenylate ratios, as single or exclusive indices of metabolic stress in A. elegantissima is questionable, given these results. Changes in absolute adenylate levels do indicate significant metabolic changes in the anemones associated with desiccation, column contraction, and starvation. PMID- 7881514 TI - Genetic diversity of cultured Penaeus vannamei shrimp using three molecular genetic techniques. AB - Three molecular genetic techniques, restriction fragment length polymorphisms (RFLPs), random amplification of polymorphic DNA (RAPD), and allozyme variability, were used to evaluate the genetic diversity of two specific-pathogen free (SPF) populations (numbers 1 and 2) and one candidate SPF population (number 4) of Penaeus vannamei developed and maintained by the U.S. Marine Shrimp Farming Program. A total of 114 individuals were tested, which included 30 each from families 1.5 and 1.6 of population 1 and from population 2, and 24 from population 4. Two HhaI mitochondrial DNA polymorphisms (A and B) were found in all the animals examined, with family 1.5 and population 2 showing type A and family 1.6 showing type B. After scoring 73 bands obtained with six different RAPD primers, the percentage of polymorphic bands was: 55% for families 1.5 and 1.6 of population 1, 48% for population 2, and 77% for population 4, suggesting that population 4 is the most polymorphic of all three populations. The allozymic variation at 30 loci showed no fixed differences in isozyme genotypes between families 1.5 and 1.6. The percentage of polymorphic loci, under the criterion that the frequency of the most common allele was less than 0.95 in each population, was 6.67%, 3.33% and 16.67% for family 1.5 of population 1, family 1.6 of population 1, and population 2, respectively. Mean heterozygosities (+/- SE) were 0.023 +/- 0.017, 0.018 +/- 0.016, and 0.064 +/- 0.026, respectively. The low levels of allozyme polymorphisms indicate that mitochondrial DNA and nuclear DNA techniques are more useful for examining genetic diversity in order to follow individual stocks within a breeding program and to correlate genotypes with desirable growth and reproductive performance of SPF P. vannamei stocks. PMID- 7881515 TI - DNA primers for amplification of mitochondrial cytochrome c oxidase subunit I from diverse metazoan invertebrates. AB - We describe "universal" DNA primers for polymerase chain reaction (PCR) amplification of a 710-bp fragment of the mitochondrial cytochrome c oxidase subunit I gene (COI) from 11 invertebrate phyla: Echinodermata, Mollusca, Annelida, Pogonophora, Arthropoda, Nemertinea, Echiura, Sipuncula, Platyhelminthes, Tardigrada, and Coelenterata, as well as the putative phylum Vestimentifera. Preliminary comparisons revealed that these COI primers generate informative sequences for phylogenetic analyses at the species and higher taxonomic levels. PMID- 7881516 TI - The pediatric cardiac care consortium--revisited. AB - BACKGROUND: The Pediatric Cardiac Care Consortium (PCCC) is a collaborative, voluntary effort of pediatric cardiologists to gather and analyze data regarding operative results. METHODS: PCCC collects information on each child who undergoes cardiac catheterization, electrophysiologic study, or a cardiac operation, or dies with a cardiac malformation. The data are analyzed annually and individual reports are created for each center. Also, representatives from the centers meet annually, and data-on the major operative procedures, including risk factors, patient profiles, and variations in adjusted mortality-are presented. RESULTS: Since PCCC's founding in 1982, overall operative mortality has decreased from 14% to 4.1% in 1991 (22% to 8.2% for infants). In one center, for example, in which overall and infant operative mortality dropped in seven years from 15% and 28% to 8% and 15%, respectively, the cardiologists and surgeon used the PCCC data to identify areas of weakness and adopt new diagnostic and treatment methods for particular cardiac conditions. They now opt for safer initial operative approaches. Another center reduced its operative mortality for coarctation of the aorta in infants after data review led to a decision to be more aggressive in early referral of infants for operations and for changes in perioperative management. DISCUSSION: Use of the study group model, in which key members work with their institution to use and interpret the data, has been an effective strategy for data dissemination. The PCCC is exploring the concept of "model centers," which would probably be procedure specific. With additional funding, the database could be expanded to include morbidity measures, functional outcome, and long-term follow-up. PMID- 7881517 TI - The abolishment of performance appraisals: Parkview's story. AB - BACKGROUND: Traditional performance appraisals, with their emphasis on individual (versus systemic or organizational) performance, are thought to undermine efforts to implement a total quality management or continuous quality improvement strategy. SEARCHING FOR A NEW PROCESS: A team charged in 1989 with the mission of improving the performance evaluation process finally determined it was simply not possible to improve a system so fundamentally flawed and recommended eliminating it. As an interim step, directors were told to dispense with scores and simply provide feedback to employees. A model for doing this was later adopted as the template for the annual feedback meeting Parkview eventually developed. A PIECE OF PAPER (APOP) IS BORN: The breakthrough, in 1992, came in realizing that an annual meeting should focus not on evaluating the employees but rather on identifying processes and systems in need of improvement. APOP IN PRACTICE: Managers and employees alike view APOP as an improvement over the old performance appraisals. One director sees APOP as a way of finding out what is going on in her department and how she can help. Another director finds that APOP not only helps him recognize the needs of good employees but also helps him to work constructively with employees having problems. HOLDING THE GAIN: Seventy-two percent of the directors have a highly favorable opinion of APOP; employees will be surveyed soon. Additional training in the APOP philosophy and process for first-line supervisors and follow-up training for leaders will be provided. PMID- 7881518 TI - A computerized system for reviewing medical records from physicians' offices. AB - BACKGROUND: Review of clinical performance in office-based care is increasing in importance as more medical care shifts to outpatient settings. Decisions made in primary care settings can save lives and limit disability through prevention and early intervention in disease. Information is needed to assess quality of care by answering such questions as whether drugs are prescribed and monitored appropriately, follow-up on serious health threats is carried out promptly, or procedures are performed for appropriate indications. Moreover, data from medical records are essential to provide important clinical information not found in the more widely used administrative data sets. Managed care organizations, too, face the need to respond to requests for objective information about the quality of primary care that they provide. Those organizations now planning assessments of primary care will need to consider the cost of obtaining information from medical record review. METHODS: The DEMPAQ Record Review System (DRRS) is a tool for peer review organizations (PROs) to use to review ambulatory care given to Medicare beneficiaries in physicians' offices. The system is described in terms of functions (activities commonly performed in the course of an office visit, such as drug prescribing), indicators (summary measures of quality for each key function of clinical care), and clinical items (for example, specific drugs or tests for each function and indicator)--a total of 263 indicators in all. A framework is provided for measuring the operational costs of a review system based on medical records. RESULTS: The costs directly associated with a fully operational review system were less than $48 per case in Iowa and Alabama and $72 per case in Maryland. On average, reviewers spent about an hour per case signed on to DRRS; average review times declined over time with practice. About half the cost of the review process is accounted for by administrative costs. Therefore, once the effort has been made to obtain records, the additional cost of abstracting more data items is relatively low. Since samples of 300-500 records suffice to measure average performance for a region or state, costs per region/state approximate $15,000 to $25,000 per measurement cycle for assessment of a wide array of clinical areas. SUMMARY: The cost of collecting information on quality of care from medical records using the review system falls within current budgets for PRO review. However, organizations planning to implement a quality improvement campaign should also consider the costs of analyzing the data, reporting information to physicians, and continuing to monitor changes in performance. PMID- 7881519 TI - Using the PDSA cycle to standardize a quality assurance program in a quality improvement-driven environment. AB - BACKGROUND: At Parkview Episcopal Medical Center (Pueblo, Colorado), QA means not only quality assurance but also quality alarms-statistical monitoring and analysis of key indicators that lead to the discovery of opportunities for continuous improvement. Data are monitored using statistical process control. Continuous improvement supports quality assurance (QA) just as it supports all other functions at Parkview. METHODS: A PDSA (Plan-Do-Study-Act) analysis form was created for use in conjunction with the data collection tool selected by the user. The data collected and analyzed are made meaningful through the standardization of formats and methods. RESULTS: Successes with this form demonstrate that QA and quality improvement (QI) can be integrated, allowing processes and outcomes to be improved. Since standardization occurred successfully in 1993, QA has been integrated into the strategic-planning process for 1994. Expectations are that duplicate reports and data gathering will be eliminated. PMID- 7881520 TI - Association of multiple sclerosis and intracranial hypertension. AB - Three patients fulfilled the diagnostic criteria for both multiple sclerosis and pseudotumor cerebri. Although coincidence is possible, intracranial hypertension may be a manifestation of demyelinating disease. PMID- 7881521 TI - Macular subretinal neovascular membrane associated with pseudotumor cerebri. AB - We report on the development of juxtapapillary subretinal neovascular membrane and permanent severe visual loss in a patient with pseudotumor cerebri. The patient was managed by a lumboperitoneal shunt. After surgery, despite resolving papilledema and intracranial pressure control, the membrane had enlarged rapidly to involve the foveal avascular zone, and resulted in rapid visual loss. The membrane slowly regressed, and was replaced by fibrous tissue at the ninth month, causing permanent severe visual loss. PMID- 7881522 TI - Hemifacial spasm. An unusual manifestation of idiopathic intracranial hypertension. AB - Increased intracranial pressure may produce a variety of clinical manifestations, some common and others rare. We present a patient with idiopathic intracranial hypertension whose initial symptom was hemifacial spasm. All signs and symptoms of intracranial hypertension resolved with acetazolamide. PMID- 7881523 TI - Chemomyectomy of the orbicularis oculi muscles for the treatment of localized hemifacial spasm. AB - OBJECTIVE: To report our experience with doxorubicin chemomyectomy as an alternative to other treatments for hemifacial spasm (HFS). DESIGN: A prospective, open study Phase I clinical trial of chemomyectomy. SETTING: A hospital-based, referral neuro-ophthalmology and oculoplastic service. PATIENTS AND METHODS: Repeated (1-6, median: 4) local injections of doxorubicin were given in the eyelids of 8 patients (5 men, 3 women, average age: 71). MAIN OUTCOME MEASURES: Eyelid strength, self-reported spasm, and duration of improvement without seeking additional or alternative treatments. RESULTS: Chemomyectomy resulted in permanent (> or = 2.5 years) orbicularis oculi weakness and relief from spasms in the treated areas in 5 patients, although 2 patients requested occasional supplementary botulinum toxin (BT) injections in the facial muscles over the cheek. One patient had a successful result for 3 years, after which spasm recurred. One patient maintains a successful result in the eyelid but had a failed microvascular decompression in the lower face. One incompletely treated patient required microvascular decompression following spread of spasms to the lower branches of the facial nerve and increased severity of the HFS. One patient required eyelid surgery because of concurrent spastic entropion. One patient treated with a higher concentration than currently used required closure of a skin ulcer. CONCLUSIONS: Doxorubicin chemomyectomy is an effective alternative to conventional therapy for properly selected patients affected by HFS, particularly older patients with relatively localized eyelid muscle spasms. The modified technique of doxorubicin chemomyectomy has developed to the point where its safety is demonstrated and its risks are known. PMID- 7881524 TI - Iatrogenic lateral rectus palsies. A series of five postmyelographic cases. AB - The objective of this study was to assess the etiology of lateral rectus palsies in patients undergoing lumbar myelograms with Iopamidol (Isovue; ER Squibb and Sons, Princeton, NJ, USA; Niopam, E Merc, UK.). An audit of the departmental orthoptic record revealed two patients who had suffered abducens palsies after myelograms. A further search revealed three additional patients who had suffered similar complications. The incidence of abducens palsy in patients undergoing myelography with the contrast agent Iopamidol was found to be 1 in 500 in around 2,500 myelograms performed under standard conditions. It would appear that lateral rectus palsy in myelography is the result of the lumbar puncture, the neurotoxic effect of the contrast agent, or a combination of the two in patients with an already compromised neurophysiologic state. This is the first series to associate this problem with Iopamidol. Although usually a serious neurologic symptom, when associated with contrast myelography using Iopamidol it is important to appreciate that such symptoms usually resolve of their own accord. PMID- 7881525 TI - Medical and surgical management of acute disseminated encephalomyelitis. AB - Two children with a recent history of viral illness developed visual loss secondary to optic neuritis. Clinical findings and neuroimaging were consistent with acute disseminated encephalomyelitis (ADEM). Markedly elevated opening pressures were noted on lumbar puncture. The patients demonstrated an initial favorable response to high-dose corticosteroid administration. Both had recurrence of symptoms after being tapered off oral corticosteroids. High-dose corticosteroids were reinstituted and a bilateral optic nerve sheath decompression was performed on one patient who developed profound visual loss. A second patient underwent a lumboperitoneal shunt. Both children had resolution of their symptoms and had a recovery of normal visual acuity. PMID- 7881526 TI - Adult expression of DeMorsier syndrome following head trauma. AB - DeMorsier syndrome is a well-described entity, which includes optic nerve hypoplasia and absence of the septum pellucidum with or without pituitary abnormalities. Patients with all three aspects of this syndrome are diagnosed in childhood due to their neuroendocrine dysfunction. We present a review of the literature and a case report of an adult diagnosed with DeMorsier syndrome when he developed neuroendocrine abnormalities after head trauma. PMID- 7881527 TI - Annual review: ocular motor systems. Part 1: Infranuclear systems. PMID- 7881528 TI - Annual review in neuro-ophthalmology. The anterior visual pathways. PMID- 7881529 TI - Effect of bed compression on high-performance liquid chromatography columns with gigaporous polymeric packings. AB - The behavior of chromatographic columns packed with gigaporous, highly cross linked styrenic particles was investigated for use in protein separation by reversed-phase chromatography at high flow velocities. Stainless-steel columns which were 3.5 or 7.5 cm long and had an inner diameter of 0.46 mm were slurry packed with 8 or 20 mm diameter spherical particles of 4000 A mean pore size by using methanol as the packing fluid. It was found that the conditions employed during the packing process have a dramatic effect on the properties of such columns and that this can be attributed in part to the deformability of the particles. An increase in the packing pressure to approximately 6000 p.s.i. (41 MPa) resulted in a higher mass-transfer efficiency for the column with a concomitant decrease in permeability. This is ascribed to a decrease in the interstitial porosity with increasing packing pressure since the experimentally measured plate heights for these columns were found to agree quantitatively with theoretical predictions that relate changes in the interstitial porosity to intraparticle mass transfer. However, the theoretically derived relationship between porosity, permeability, and efficiency does not hold for columns packed at pressures higher than 6000 p.s.i., in which case the total column porosity was found to be high while the permeability and column efficiency were low. This behavior is explained by the formation of a low-porosity layer of highly compressed particles at the downstream end of the column during high pressure packing so that the assumption of axially uniform column properties used in the theoretical approach leads to very large errors. PMID- 7881531 TI - Preparative capillary zone electrophoresis of synthetic peptides conversion of an autosampler into a fraction collector. AB - Preparative capillary zone electrophoresis of three synthetic peptides was performed either manually or automatically by simple manipulations of a commercial electropherograph that is equipped only with an autosampler without any built-in fraction collection capability. Manual fraction collection was achieved by replacing the outlet (cathode) beaker with a microcentrifuge tube, and automatic fraction collection was accomplished by converting the electropherograph's autosampler into a fraction collector. The latter was easily achieved mainly by the use of an extension wire, which completed the electrical circuit and facilitated fraction collection either at a specified time or within fixed time intervals. PMID- 7881530 TI - Sorption kinetics and breakthrough curves for pepsin and chymosin using pepstatin A affinity membranes. AB - Isotherms and kinetic parameters for pepsin and chymosin sorption to immobilized pepstatin A were measured in batch experiments. The measured single-solute parameters were used in an affinity-membrane model which included competitive sorption kinetics, axial diffusion and dead volume mixing. The predictions made using the affinity-membrane model matched the experimental breakthrough curves, whereas predictions made using local-equilibrium theory were a distinct mismatch. The performance of affinity-membrane separations was dominated by slow sorption kinetics. PMID- 7881533 TI - Determination of atropine and obidoxime in automatic injection devices used as antidotes against nerve agent intoxication. AB - A capillary gas-liquid chromatographic (GLC) and an ion-pair high performance liquid chromatographic (HPLC) method were developed for the assay of atropine sulphate and obidoxime chloride from a parenteral solution in commercial automatic injection devices. The injectors are aimed for the emergency treatment of poisoning by nerve agents. The two-step GLC method consists of extraction of atropine as a free base prior to GLC analysis using scopolamine as an internal standard. Obidoxime is determined directly in a diluted sample solution by reversed-phase HPLC using sodium 1-heptanesulphonate as a counter ion in the mobile phase. The relative standard deviation (R.S.D.) was 1.81% for the GLC procedure with injectors containing only atropine and 2.37% for the GLC of atropine in atropine-obidoxime injectors. The R.S.D. for the HPLC procedure of obidoxime in atropine-obidoxime injectors was 0.82%. The corresponding R.S.D.s for the sampling of atropine-obidoxime injectors were 0.36% and 0.27%. The coefficient of determination (r2) was 1.000 for both methods. The recoveries at the target concentration averaged 101.0% and 98.7% with a standard error of the mean of 0.30 for both methods. The retention times for atropine and obidoxime were 6.27 and 4.29 min, respectively. PMID- 7881532 TI - Combined pH gradient and anion-exchange high-performance liquid chromatographic separation of oligodeoxyribonucleotides. AB - A novel method of elution using a pH gradient to separate small thymidine- and guanosine-containing oligonucleotides on a Pharmacia Mono Q HR anion-exchange column is described. The method is based on the alkaline titration of ring protons of the thymine and guanine base moieties and results in excellent separations of di-, tri- and tetranucleotides that either are not resolved in salt gradients near neutral pH or require long elution times when salt gradient elution is used with strongly alkaline eluents. PMID- 7881534 TI - Amphiphilic agarose-based adsorbents for chromatography. Comparative study of adsorption capacities and desorption efficiencies. AB - A number of hydrophobic derivatives attached to cross-linked agarose were studied as protein adsorbents. Differences in the adsorption and desorption behaviour were determined as functions of type and concentration of selected salts. Whereas octyl- and phenyl-Sepharose adsorb serum albumin preferentially, pyridyl-S agarose shows a much stronger preferential affinity for IgG in the presence of high concentrations of lyotropic salts, such as sulphates. In contrast to pyridyl S-agarose, a large portion of proteins remained fixed to octyl- and phenyl Sepharose after extensive washing with 1 M NaOH. PMID- 7881535 TI - High-precision gas chromatography-combustion isotope ratio mass spectrometry at low signal levels. AB - Precision and accuracy of gas chromatography-combustion isotope ratio mass spectrometry are investigated for sample levels down to about 5 pmol C in fatty acid methyl ester mixtures spanning 1000-fold in concentration. Precision and accuracy of isotope ratios diverge rapidly for conventional summation methods, and become unusable below 30 pmol material on column. At lower levels, mean isotope ratios were statistically different from reference values indicating bias as well as poor precision. In contrast, curve fitting, using the exponentially modified Gaussian line shape, gives improved precision for most peaks and useful results down to 3 pmol. The curve-fitting algorithm was also less sensitive to signal integration time than the summation method. These data indicate that curve fitting may be the method of choice for integration of noisy data when high precision isotope ratios are desired. PMID- 7881536 TI - Gas chromatographic separation of bile acid 3-glucosides and 3-glucuronides without prior deconjugation on a stainless-steel capillary column. AB - A method for the gas chromatographic (GC) separation of the 3-glucoside and 3 glucuronide conjugates of bile acids without the necessity for a hydrolytic step is described. The bile acid glycosides were derivatized to their complete methyl ester trimethylsilyl (Me-TMS) or methyl ester dimethylethylsilyl (Me-DMES) ether derivatives, which in turn were chromatographed on an inert and thermostable stainless-steel capillary column, Ultra ALLOY-1 (HT), coated with a thin film (0.15 micron) of chemically bonded and cross-linked dimethylsiloxane. They exhibited a single peak of the theoretical shape without any accompanying peaks due to thermal decomposition, even at oven temperatures of 320-330 degrees C. Excellent GC separation of isomeric bile acid glycosides was achieved by the combined use of suitable derivatives and column. This method, which does not need the prior deconjugation of the glycosidic moiety, could be usefully applied to biosynthetic and metabolic studies of bile acids in biological materials. PMID- 7881537 TI - Gas chromatographic determination of triclopyr in fruits and vegetables. AB - This research was comprised of two parts: quantitative analyses, and confirmatory test. In the quantitative analyses, five classes of fruits and vegetables comprising 10 individual commodities were fortified with triclopyr herbicide at 0.4 and 0.8 ppm level. Triclopyr was extracted from the matrices and derivatized separately to 2-chloroethylene ester with 2-chloroethanol-BCl3 and methyl ester with diazomethane. The esters were then quantitated by GC-ECD and GC-NPD. The GC ECD recoveries for 2-chloroethylene ester were 100.0% and 100.7% at 0.4 ppm and 0.8 ppm fortification levels, respectively, whereas methyl ester recovery was 103.9% at 0.4 ppm fortification level. Similarly, the GC-NPD recoveries for 2 chloroethylene ester were 99.0% and 97.9% at 0.4 ppm and 0.8 ppm fortification levels respectively, whereas methyl ester recovery was 102.0% at 0.4 ppm fortification level. In the confirmatory test, the 2-chloroethylene ester was introduced into a GC-ion trap. The EI mass spectrum was then interpreted based on the criteria of molecular ion, isotopes, base ion, characteristic ions and the nitrogen rule. Compared to existing methods, this method has reduced partition solvents to nearly one-tenth. In addition, this method proved to be simple, fast, safe and accurate. PMID- 7881538 TI - Separation of estrogens by micellar electrokinetic chromatography. AB - Capillary electrophoresis of the sex hormone estrogens using different buffer components was investigated. Free zone electrophoresis with 10 mM phosphate buffer (pH 11.5) or 10 mM phosphate buffer with 10-20% methanol was not effective in separating the ten estrogens used in this study. However, nine estrogens were resolved by micellar electrokinetic chromatography using a 10 mM borate buffer (pH 9.2) containing 100 mM sodium cholate. In addition, some estrogens were partially separated using sodium dodecyl sulfate (SDS) micellar buffers; however, the addition of modifiers such as organic solvents or cyclodextrins improved resolutions significantly. Using a 10 mM phosphate buffer (pH 7.0) containing 50 mM SDS and 20% methanol, or a 10 mM borate buffer (pH 9.2) containing 50 mM SDS and 20 mM gamma-cyclodextrin, all ten of the tested estrogens were separated. However, the cyclodextrin-modified buffer allowed faster separation. PMID- 7881539 TI - Uniform-size hydrophobic polymer-based separation media selectively modified with a hydrophilic external polymeric layer. AB - A simple procedure for the preparation of macroporous hydrophobic styrene divinylbenzene polymeric separation media with a hydrophilic outer surface has been developed. A hydrophilic monomer and water-soluble polymerization initiator are added to the reaction mixture during the final polymerization step of the preparation of size-monodisperse particles. Because the hydrophobic styrene divinylbenzene framework of the beads is already formed, and the hydrophilic monomer does not penetrate the pores of the beads that are filled with a hydrophobic porogen, the hydrophilic layer is formed only at the surface of the beads. The hydrophilic monomers used included glycerol monomethacrylate and glycerol dimethacrylate and toluene was used as the porogen for the poly(styrene co-divinylbenzene) beads. Comparative experiments involving beads with or without a hydrophilic medium showed that the separation selectivity of the media towards hydrophobic solutes remains unchanged. However, the modified medium with a hydrophilic layer could be used to analyse mixtures that also contained large peptide molecules as these do not adsorb at its surface as is the case with the unmodified hydrophobic beads. PMID- 7881540 TI - Oligonucleotide model with non-identical complementary strands for chromatographic studies of structure-dependent photosusceptibility. AB - In a previous work, we used a quantitative chromatographic analysis of two self complementary oligonucleotides to correlate the conformational differences between the oligonucleotide duplexes and photochemical susceptibilities of constituent oligomers. In this work we describe a new double-stranded oligonucleotide model with non-identical complementary strands. To separately analyze photoproducts in two strands, one of them is used in a partially protected form (the hydrophobic 5'-dimethoxytrityl group uncleaved). Using a reversed-phase column, the oligomers and products of their UV photomodification are separated into two groups of peaks. This facilitates the quantitation of photoproducts in each of the complementary strands. Three 15-mer oligonucleotides, 5'-TTTTTAT-TAAATATA-3' (F5), 5'-AAAAATAATTTATAT-3' (F6) and 5' TATATTTAATAAAAA-3' (F7) form the parallel-stranded (ps) F5.F6 and the ordinary antiparallel-stranded (aps) F5.F7 duplexes. For these particular sequences, the rate of cyclobutane thymine dimer formation in the ps DNA has been estimated as ca. 1.5-2 times that in the ordinary aps DNA. PMID- 7881541 TI - Growth and guidance of the fungal hypha. PMID- 7881542 TI - Protein phosphorylation in cyanobacteria. PMID- 7881543 TI - Phosphorylation of membrane proteins in response to temperature in an Antarctic Pseudomonas syringae. AB - Temperature-dependent phosphorylation and dephosphorylation of membrane proteins was studied in vitro in a number of psychrotrophic Antarctic bacteria which grow between 0 and 30 degrees C. One of them, a Pseudomonas syringae isolate, was studied in detail and was found to have three membrane proteins of molecular mass 30, 65 and 85 kDa which were phosphorylated differently in response to low and high temperatures. The 65 kDa protein was phosphorylated only at lower temperatures (between 0 and 15 degrees C). The 30 kDa protein was phosphorylated more at higher temperatures and was possibly a histidine kinase. This protein was present in all the psychrotrophic Pseudomonas species studied and in Sphingobacterium antarcticus. A possible role for these proteins in sensing environmental temperature is proposed. PMID- 7881544 TI - Transposon mutagenesis of Nostoc sp. strain ATCC 29133, a filamentous cyanobacterium with multiple cellular differentiation alternatives. AB - Nostoc sp. strain ATCC 29133 (PCC 73102; Nostoc 29133) is a symbiotically competent, facultatively heterotrophic, diazotrophic cyanobacterium with the capacity to differentiate specialized cells such as heterocysts, akinetes and hormogonial filaments. We have optimized several methods for physiological and molecular genetic analysis of Nostoc 29133. By use of a Tn5 derivative, Tn5-1063 (Km(r)Bm(r)Sm(r)), delivered by conjugation from Escherichia coli, antibiotic resistant mutants of Nostoc 29133 were generated at a frequency of approximately 1 x 10(-6), 0.4% of which expressed a nitrogen fixation (heterocyst) defective phenotype. Mutant strain UCD 328 was isolated after co-culture of 86 Nostoc 29133::Tn5-1063 clones with the symbiotic plant partner, Anthoceros punctatus; strain UCD 328 expressed a symbiotic phenotype of increased frequency of hormogonia-dependent infection. The transposon and flanking genomic DNA was recovered from strain UCD 328, the mutation and phenotype reconstructed by homologous recombination in Nostoc 29133, and the transposition site identified from a Nostoc 29133 genomic library. Transposon mutagenesis has thus provided the means for isolation and identification of developmental and symbiotic-specific genes of Nostoc 29133. PMID- 7881545 TI - Studies of the biosynthesis of tentoxin by Alternaria alternata. AB - Biosynthesis of the phytotoxin, tentoxin, its regulation and the enzymic synthesis steps were studied in vivo and in vitro. The physiology of biosynthesis of tentoxin in vivo was investigated by using sections of mycelial mats incubated in buffer. Differentiated mycelia could be studied under defined conditions. The de novo synthesis of tentoxin was measured by incorporation of [U-14C]leucine into tentoxin. The investigation system was stable for 10 h. Biosynthesis and the growth of biomass started before day 5 of culture, with the maximum between days 9 and 12. After this, biosynthesis quickly declined. pH values about 7 were optimal, and pH values above and below this led to an increased release of tentoxin stored in the cells. The formation of tentoxin by older mycelia was not regulated by acetate, phosphate or glucose, which was not utilized. Precursor amino acids, applied at the start of the culture, slightly activated the synthesis of tentoxin. Older mycelia were inhibited. Substances from the host plant (Brassica chinensis) reduced the de novo synthesis of tentoxin. Enzyme separation studies suggested that biosynthesis of tentoxin involves a multienzyme (> or = 400 kDa), which is a polyfunctional protein without subunits. Experiments suggested that the synthetase contains active SH-groups and an integrated activity of methyltransferase. The precursor amino acids are activated by ATP and bound at the enzyme. N-Methylation occurs with the enzyme-bound amino acids or during the elongation of the growing peptide chain. Methionine is the primary donor of the methyl groups, but the immediate methylation reaction needs 5 adenosyl methionine (SAM). The methylation is essential for the continuation of biosynthesis. The elongation proceeds either stepwise from glycine by binding alanine/methylalanine, phenylalanine/methylphenylalanine and leucine or by formation and linkage of two dipeptides glycine-alanine/methylalanine and phenylalanine/methylphenylalanine-leucine. At the end of this process dihydrotentoxin, the direct precursor of tentoxin, is released from the synthetase probably by cyclization. Independent of this first enzyme, dihydrotentoxin is transformed into tentoxin. This last reaction step is reversible. The rate of transformation of dihydrotentoxin to tentoxin is higher, but in this direction the native turnover is relatively low.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7881546 TI - Analysis of Saccharomyces cerevisiae proteins induced by peroxide and superoxide stress. AB - Exponentially growing Saccharomyces cerevisiae cells are more sensitive to oxidants such as hydrogen peroxide and superoxides than stationary phase cells. Using disruption mutations in the genes encoding the two S. cerevisiae superoxide dismutases, we show that the principal mechanism of toxicity of redox-cycling compounds, such as menadione and plumbagin, is via the production of superoxide anions. Using two-dimensional polyacrylamide gel electrophoresis we have compared the pattern of protein expression in cells labelled with L-[35S]methionine and stressed with either H2O2 or menadione. Three groups of proteins were evident: those whose levels are elevated by both H2O2 and menadione, and those specifically induced by either H2O2 or menadione. Experiments with promoter fusions demonstrated that one of the heat inducible forms of HSP70 (SSA1) was inducible with H2O2. Furthermore, induction of the yeast H2O2-responsive TRX2 promoter by menadione required the metabolism of menadione. PMID- 7881547 TI - Comparison of outer-membrane proteins of Pasteurella haemolytica expressed in vitro and in vivo in cattle. AB - Outer-membrane protein (OMP) profiles of two serotype A1 isolates of Pasteurella haemolytica were compared by SDS-PAGE and Western blotting with bovine convalescent serum after growth (a) in vitro under iron-sufficient and -deficient conditions, (b) in vivo in the lungs of experimentally infected calves and (c) in vivo in diffusion chambers implanted into the peritoneal cavities of calves. Lung grown bacteria differed from iron-sufficient in vitro-grown bacteria in having enhanced expression of the previously recognized 71, 77 and 100 kDa iron regulated proteins, reduced expression of 18, 31, 39.5 and 50 kDa proteins, and expression of a 19 kDa protein. Differences were also apparent in the Western blot profiles of OMPs of in vitro- and lung-grown bacteria. These included the apparent lack of recognition of the 100 kDa protein in the lung-grown bacteria, but not in the in vitro-grown bacteria, and more intense staining of a 47 kDa protein in in vitro-grown bacteria, but not in lung-grown bacteria. The OMP profiles of the chamber-grown bacteria resembled those of the lung-grown bacteria in that expression of the 18, 19, 31 and 39.5 kDa proteins was similar. These similarities demonstrated that the chamber-grown bacteria had adapted to the in vivo environment, and that growth conditions within the chambers resembled, but not perfectly, those within the lungs. For example, expression of the three iron regulated OMPs was very low in the chamber-grown bacteria compared to the lung grown bacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881548 TI - Expression of the Bordetella pertussis P.69 pertactin adhesin in Escherichia coli: fate of the carboxy-terminal domain. AB - The mature pertactin protein (P.69) of Bordetella pertussis can be isolated from the bacterial cell surface as a polypeptide with an apparent molecular mass of 69,000 Da as determined by sodium dodecyl sulphate gel electrophoresis. However the open reading frame of prn, the pertactin gene, encodes a polypeptide with a predicted molecular mass of 93,478 Da, referred to as P.93. Expression of the prn gene in Escherichia coli leads to the synthesis of the full-length P.93 polypeptide, which is rapidly processed to the mature P.69 protein located at the cell surface. The P.93 precursor polypeptide is processed at both termini. A 34 amino acid long signal sequence is removed from the amino-terminus and a polypeptide sequence of about 30,000 Da (P.30) is cleaved from the carboxy terminus. Deletion of the 3' region of prn, encoding P.30, results in the expression of an intracellular form of P.69. Antiserum which recognizes P.30 was raised using synthetic peptides based on the primary amino acid sequence of the region. This anti-P.30 serum was used in a Western blot analysis of fractionated cells of B. pertussis and E. coli harbouring the intact prn gene. The P.30 polypeptide was readily detected in outer membrane fractions prepared from both of these bacterial species, although it could not be shown to be exposed at the cell surface. PMID- 7881549 TI - Serum-sensitive mutation of Francisella novicida: association with an ABC transporter gene. AB - Francisella novicida is a facultative intracellular pathogen that can survive and grow in macrophages by preventing phagolysosomal fusion. In this study in vitro cassette mutagenesis was used to generate a library of insertion mutants of F.novicida. Two related mutants, KM14 and KM14S, initially identified as defective for growth in macrophages, were found to be sensitive to serum. These mutants were also found to grow approximately 1000-fold less well in the livers and spleens of infected mice. We cloned a genetic locus that was presumably mutagenized in these mutants and found that it included genes that had high similarity in their deduced amino acid sequence to those of msbA and orfE of Escherichia coli. The former is a member of the superfamily of ABC transporter proteins. We named the corresponding genes in F. novicida, valAB. Integration of a cloned valAB locus into the chromosome of KM14S partially restored the serum resistance phenotype found in wild-type F. novicida. PMID- 7881550 TI - Occurrence of chromosome rearrangements during the fusion process in the imperfect yeast Candida albicans. AB - Auxotrophic derivatives of three strains of the pathogenic yeast Candida albicans of different origins, including 1006 derived from CBS5736, A5153 derived from FC18 and NARA2 derived from NUM961, were used in spheroplast fusion experiments. The DNA content of the prototrophic fusion product obtained following fusion between strains 1006 and A5153 approximated to the sum of those of the parents, but was variable when NARA2 was used as the parent for fusion. Chromosome-sized DNA molecules of the fusion derivatives were separated by pulsed-field gel electrophoresis to examine whether either or both of the chromosome-sized DNA molecules of each parent were transferred into the fusion derivatives. In the fusion derivatives obtained following fusion between strains 1006 and A5153, nearly the full complement of chromosomes was shown to be transferred, but partial transfer of chromosomes occurred in the fusion derivatives that were obtained following fusion between strains NARA2 and A5153. Results indicated that chromosome loss also occurred when these two strains were fused. Variations in the size of R chromosomes, the rDNA-containing chromosomes, were observed in all fusion derivatives tested, indicating high-frequency recombination between R chromosomes during the fusion process. PMID- 7881551 TI - Cloning and expression in Escherichia coli of DNA encoding a 60 kDa stress protein of Mycobacterium paratuberculosis, the causative agent of Johne's disease. AB - Polymerase chain reaction (PCR) was used to generate DNA encoding a 60 kDa stress protein of Mycobacterium paratuberculosis using primers complementary to sequences at the 5' and 3' ends of 60 kDa stress protein genes (encoding the '65 kDa antigens') of M. leprae and M. tuberculosis. The predicted PCR product of 1.8 kb contained the entire coding sequence of an M. paratuberculosis 60 kDa stress protein, with non-coding regions of 124 bp and 1 bp at the 5' and 3' ends, respectively. DNA encoding the entire ORF for the 60 kDa stress protein, as well as thrombin and Factor Xa proteolytic cleavage sites, was ligated into the bacterial expression vector pGEX-2T and used to transform Escherichia coli strain JM83. Transformed bacteria, induced by IPTG, expressed an 85 kDa fusion protein comprising glutathione S-transferase (GST) and M. paratuberculosis 60 kDa stress protein. This fusion protein was purified by adsorption to glutathione-agarose beads and shown to cross-react in Western blot analysis with an anti mycobacterial 60 kDa stress protein monoclonal antibody. Recombinant M. paratuberculosis 60 kDa stress protein was liberated from GST by proteolytic cleavage with either thrombin or Factor Xa enzyme. Authenticity of liberated recombinant stress protein was confirmed by N-terminal amino acid sequencing. PMID- 7881553 TI - Analysis of different DNA fragments of Corynebacterium glutamicum complementing dapE of Escherichia coli. AB - In Corynebacterium glutamicum L-lysine is synthesized simultaneously via the succinylase and dehydrogenase variant of the diaminopimelate pathway. Starting from a strain with a disrupted dehydrogenase gene, three different-sized DNA fragments were isolated which complemented defective Escherichia coli mutants in the succinylase pathway. Enzyme studies revealed that in one case the dehydrogenase gene had apparently been reconstituted in the heterologous host. The two other fragments resulted in desuccinylase activity; one of them additionally in succinylase activity. However, the physical analysis showed that structural changes had taken place in all fragments. Using a probe derived from one of the fragments we isolated a 3.4 kb BamHI DNA fragment without selective pressure (by colony hybridization). This was structurally intact and proved functionally to result in tenfold desuccinylase overexpression. The nucleotide sequence of a 1966 bp fragment revealed the presence of one truncated open reading frame of unknown function and that of dapE encoding N-succinyl diaminopimelate desuccinylase (EC 3.5.1.18). The deduced amino acid sequence of the dapE gene product shares 23% identical residues with that from E. coli. The C. glutamicum gene now available is the first gene from the succinylase branch of lysine synthesis of this biotechnologically important organism. PMID- 7881552 TI - The Escherichia coli dsbA gene is partly transcribed from the promoter of a weakly expressed upstream gene. AB - The dsbA gene of Escherichia coli encodes a periplasmic enzyme which catalyses disulfide bond formation. Analysis of its surrounding DNA region showed that it is preceded by an open reading frame, orfA, of 984 nucleotides. The intergenic region (19 nucleotides) carries no typical transcription termination signals. dsbA is transcribed from two promoters, the first (P1) lies in the distal part of orfA, and the second (P2) just upstream from orfA. Using a plasmid-borne dsbA::TnphoA fusion and an orfA::omega insertion, each promoter was shown to contribute equally to dsbA transcription. The disruption of the single chromosomal copy of orfA by omega more drastically reduced the amount of DsbA in the periplasmic space. Such a reduction of the DsbA pool, however, did not change the activities of the AppA, Agp and PhoA periplasmic phosphatases, which all require disulfide bond formation, even when the enzymes were produced from multicopy recombinant plasmids. Thus, in a wild-type strain, DsbA is far from being in limiting amounts for physiological requirements. The orfA gene product was identified as a weakly expressed 39 kDa cytoplasmic protein, but it is not involved in the overall mechanism of disulfide bond formation. PMID- 7881555 TI - Cloning and characterization of polyketide synthase genes for jadomycin B biosynthesis in Streptomyces venezuelae ISP5230. AB - Hybridizing fragments in the genomic DNA of Streptomyces venezuelae ISP5230, which produces the jadomycin group of angucycline antibiotics, were detected by probing with actI DNA from Streptomyces coelicolor A3(2). The hybridizing regions were isolated from a 16.5 kb insert of S. venezuelae DNA recovered from a genomic library cloned in a lambda replacement vector. Subcloning and sequencing of a 4.8 kb segment of the insert, containing regions hybridizing to actIII as well as actI, identified five open reading frames (ORFs). The deduced polypeptide products of the ORFs closely resemble in sequence the components of streptomycete type-II polyketide synthases (PKSs): the ORF1 product corresponds to the ketoacyl synthase, and the ORF2 product to a polypeptide closely related to the ketoacyl synthase and involved in determining chain length; the ORF3 product matches the acyl carrier protein; ORF4 encodes a bifunctional cyclase/dehydrase; and ORF5 encodes a ketoreductase. Integration into the chromosomal DNA of a plasmid containing a segment of the ORF2-ORF4 region severely depressed jadomycin B biosynthesis; since the integrant showed no change in growth or spore pigmentation, the cloned PKS genes are presumed to encode enzymes in the pathway for jadomycin biosynthesis. PMID- 7881554 TI - Possible involvement of the lysine epsilon-aminotransferase gene (lat) in the expression of the genes encoding ACV synthetase (pcbAB) and isopenicillin N synthase (pcbC) in Streptomyces clavuligerus. AB - Streptomyces clavuligerus produces the beta-lactam antibiotics penicillin N, O carbamoyldeacetylcephalosporin C and cephamycin C. We characterized a wild-type DNA region which restores antibiotic formation to a mutant strain named NP1, previously shown to exhibit depressed activities for two early enzymes of cephalosporin synthesis, delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) and isopenicillin N synthase (IPNS). L-Lysine epsilon aminotransferase (LAT) assays and alpha-AAA feeding experiments suggested that strain NP1 is a lat mutant. NP1 recovered LAT, ACVS and IPNS activities when transformed with the cloned region. DNA sequencing showed that this region encodes the entire LAT gene (lat), required for the conversion of L-lysine to the beta-lactam precursor L-alpha-aminoadipic acid (alpha-AAA), as well as the upstream half of the ACVS gene (pcbAB). The activities of ACVS and IPNS appear to depend upon LAT expression. Gene fusions constructed to investigate promoter activities in the cloned region support a model of interdependence in the expression of the genes for LAT, ACVS and IPNS (pcbC). PMID- 7881556 TI - Characterization of the major catalase from Streptomyces coelicolor ATCC 10147. AB - Streptomyces coelicolor ATCC 10147 produced catalases whose electrophoretic mobility varied depending on the growth phase in liquid culture. Polyacrylamide gel electrophoresis of cell extracts resulted in six catalase activity bands, which were designated Cat1 to Ca6. Of these, Cat4 appeared during all growth phases, whereas Cat1 appeared only during the stationary phase. Catalase deficient mutants were screened by the H2O2 bubbling test following NTG mutagenesis. In all the non-bubbling mutants tested, the Cat4 activity band significantly decreased or disappeared, suggesting that Cat4 is the major catalase. Cat4 was purified to electrophoretic homogeneity and some of its properties analysed. The enzyme has a native molecular mass of 225 kDa, as determined by gel permeation column chromatography, and consists of four identical subunits of 57 kDa, as determined by SDS-PAGE. The enzyme contains 2.6 molecules of protohaem IX per tetramer, as indicated by the absorption spectrum. It was not reducible by sodium dithionite and exhibited no peroxidase activity with o-dianisidine as the substrate. All these characteristics, as well as inhibitor studies, indicate that the major vegetative catalase in S. coelicolor, unlike E. coli vegetative catalase, is a member of the typical monofunctional catalases found in eukaryotes and some bacteria. PMID- 7881558 TI - Metabolic cooperation in oral microbial communities during growth on mucin. AB - Hog gastric mucin has been used as a model glycoprotein to determine the role of particular glycosidases produced by different oral bacteria in the development of stable, diverse microbial communities. The patterns of glycosidase and protease activity were determined in pure cultures of ten representative species of oral bacteria using synthetic substrates. A five-member mixed culture was established in a chemostat, comprising species with minimal glycosidase and protease activity, in which hog gastric mucin was the major carbon and energy source. Introduction of additional species with novel enzyme activities (e.g. sialidase, alpha-fucosidase and endopeptidase) led to their establishment within the community to make communities with seven, eight, nine and ten members and resulted in an increase in the total viable counts of the microbial consortium. This increase in viable count was made up of the numbers of the newly added species as well as from a rise in the numbers of the existing community members. This result suggested that glycoprotein catabolism involved the synergistic and concerted action of several species with overlapping patterns of enzyme activity. Such metabolic cooperation results in the liberation of additional nutrients, and this may help to maintain the characteristic diversity of resident microbial communities found in many natural habitats. PMID- 7881557 TI - Cloning and expression in Escherichia coli of the nahA gene from Porphyromonas gingivalis indicates that beta-N-acetylhexosaminidase is an outer-membrane associated lipoprotein. AB - Porphyromonas gingivalis has been implicated in human periodontal diseases. It expresses a number of exoglycosidase enzymes capable of hydrolysing host proteoglycan residues. As a first stage to explore the role of these enzymes in periodontal tissue damage, the nahA gene of P. gingivalis W83, which encodes beta N-acetylhexosaminidase (beta-Nahase), was cloned. The gene was expressed poorly in Escherichia coli, but increased expression was achieved by cloning the nahA gene downstream of the tac promoter. Southern blot analysis revealed that nahA was present as a single copy, and it was found in all the other P. gingivalis strains tested. In contrast, sequences homologous to nahA were not detected in either P. endodontalis or P. asaccharolytica. The nahA gene was 2331 bp long and encoded a beta-Nahase enzyme of 777 amino acids with a predicted molecular mass of 87 kDa. A characteristic signal peptide for an acylated lipoprotein was present at the amino-terminus, suggesting that the mature beta-Nahase is a lipoprotein. The predicted amino acid sequence of the P. gingivalis beta-Nahase shared homology with the catalytic domains of the human beta-Nahase enzyme and the chitinase of Vibrio harveyi, suggesting a common catalytic mechanism. PMID- 7881559 TI - Regulation of 2-deoxyglucose phosphate accumulation in Lactococcus lactis vesicles by metabolite-activated, ATP-dependent phosphorylation of serine-46 in HPr of the phosphotransferase system. AB - Lactococcus lactis takes up glucose and the nonmetabolizable glucose analogue 2 deoxyglucose (2DG) via the phosphotransferase system and extrudes the accumulated sugar phosphates in a process apparently dependent on a cytoplasmic sugar phosphate phosphatase. Uptake of 2DG into L. lactis vesicles was shown to be dependent on an energy source, effectively provided by intravesicular phosphoenolpyruvate (PEP). 2DG phosphate (2DG-P) accumulation in these vesicles was not inhibited, and preaccumulated 2DG-P was not released from them, upon electroporation of fructose 1,6-diphosphate (FDP), gluconate 6-phosphate or 2 phosphoglycerate into the vesicles. Intravesicular but not extravesicular wild type HPr of Bacillus subtilis alone stimulated uptake, but in the presence of any one of these metabolites, it prevented accumulation of 2DG-P. Intravesicular H15A mutant HPr inhibited uptake and allowed further inhibition of 2DG-P accumulation in the presence of the intravesicular metabolites. Intravesicular S46A mutant HPr stimulated uptake but could not promote inhibition in the presence of the phosphorylated metabolites. The S46D mutant HPr protein promoted regulation, even in the absence of a metabolite. The Vmax but not the Km value for 2DG uptake was affected. Accumulation of the natural, metabolizable substrates of the lactose, glucose, mannose and ribose permeases was inhibited by wild-type HPr in the presence of FDP or by S46D mutant HPr. The results establish that HPr serine phosphorylation by the ATP-dependent, metabolite-activated HPr kinase selectively determines the levels of sugar accumulation via the glucose and lactose permeases in L. lactis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881560 TI - Violence in hospitals: how nurses cope. PMID- 7881561 TI - Colors of the spectrum. Reproductive medicine spawns challenging new nursing specialty. PMID- 7881562 TI - Beyond the yearly mammogram. PMID- 7881563 TI - When you're suddenly unemployed. PMID- 7881564 TI - Management perspectives. As a nursing care coordinator, I have responsibilities to my director of nursing, my staff, and the patients on my unit. PMID- 7881565 TI - Research: expanding the dimensions of women's health. PMID- 7881566 TI - Jewish nurses who shaped history. PMID- 7881567 TI - The youngest victims of domestic violence. Interview by Mary Jane Zusy. PMID- 7881568 TI - Colors of the spectrum. Perinatal clinical nurse specialists. PMID- 7881569 TI - Advancing your practice. PMID- 7881570 TI - Hopkins blends advanced practice roles. PMID- 7881571 TI - Management perspectives. I am a new hired clinical nurse specialist in the emergency department (ED). PMID- 7881573 TI - Using a dose of humor for better health. PMID- 7881572 TI - RNs at the crossroads in advanced practice. PMID- 7881574 TI - George Mason RN students meet community needs. PMID- 7881575 TI - Colors of the spectrum. Nurse psychotherapist. PMID- 7881576 TI - Tact, craft, and ingenuity. PMID- 7881577 TI - Management perspectives. I am a nurse manager in a university hospital clinic. PMID- 7881578 TI - Occupational health nursing: from black lung to white collar. PMID- 7881580 TI - Decisions at the beginning of life. PMID- 7881579 TI - Colors of the spectrum. Visiting oncology clinical specialist. PMID- 7881581 TI - Management perspectives. What are the most pressing ethical issues facing nurse administrators in today's health care climate? PMID- 7881582 TI - Nursing and ethics across the life span. PMID- 7881583 TI - Sunset for H-1 visa law? PMID- 7881584 TI - Hearing on nursing funds for education and research. PMID- 7881585 TI - [Toward a scientific approach to blood surveillance]. PMID- 7881586 TI - [Epidemiological support in blood surveillance]. AB - "Hemovigilance" is a continuous and standardized system for data collection and analysis, and diffusion of results to clinical and public health decision makers. This system has different objectives than clinical and epidemiological research on labile blood products. A published study of characteristics of donors that are infected by the human immunodeficiency virus illustrates the need for information on temporal patterns of events relevant to transfusion safety. Two cohort studies on post-transfusion hepatitis and a randomized study on cytomegalovirus infections illustrate the importance of surveillance for detecting events that are causally linked to transfusion. The interest of "hemovigilance" is also discussed in the context of epidemics and new hazards, when surveillance is the only possibility of designing ad-hoc epidemiologic studies, yielding results within delays compatible with decisions that are timely and effective for improving transfusion safety. PMID- 7881587 TI - Risk in blood transfusion with reference to the present situation in the United Kingdom. PMID- 7881588 TI - [Risk of the appearance of inhibitors linked to the administration of factors VIII and IX. Review of the literature]. AB - Factors VIII and IX administration exposes haemophiliac patients to the risk of inhibitor development which reduces treatment efficacy. Methods and results of 17 studies (transversal and longitudinal) and of one clinical trial dealing with haemophilia A and of 3 studies dealing with haemophilia B were reviewed. Besides differences in study design, lack of method standardisation complicates comparison between studies. In patients with haemophilia A, prevalence of inhibitors ranges from 4 to 18% (5 studies), and incidence between 3 and 39/1,000 person-years (7 studies). Cumulative age incidence is above or equal to 20% after 6 years of age (4 studies). Cumulative incidence by exposure days is estimated at 22% at 100 exposure days in a retrospective cohort observed between 1975 and 1992, and above or equal to 36% at 25 exposure days in two prospective cohorts of patients receiving recombinant factor VIII products. The new European regulation dealing with stable blood products will make the evaluation of new products by clinical trials mandatory. With The National therapeutic Follow up of Haemophiliacs which begun in October 1994, following a decision by the French Minister of Health, the adverse effects in patients receiving factor VIII and IX which have been approved for sales will be evaluated. PMID- 7881589 TI - [Molecular approach to the immunology and biology of blood groups]. PMID- 7881590 TI - [Warning systems: past, present, and future]. PMID- 7881591 TI - [Preventing deficiencies in the transfusion process]. AB - The methods of system reliability analysis represent an interesting set of tools used to follow the so-called "transfusion process", defined as all the steps from donors sensitization to recipients follow-up. FMECA, (Failure Mode Effects and Criticality Analysis), can be used as a prevention tool, independently of any dysfunction in the process. Of course, it can equally be used following a failure, in order to analyse the causes and to apply the specific corrections. Quality insurance, system reliability analysis, epidemiologic surveillance and safety monitoring operate in synergy. These three issues pertaining to transfusion safety constitute a dynamic system. PMID- 7881592 TI - [Blood transfusion and quality assurance]. AB - Administrating safe blood products and being able to produce the evidence of procedures correctly employed, is today vital for healthcare professionals. Industrial quality assurance is an appropriate answer to this problem. Indeed, this approach allows the mastering of a processing system thanks to the combination of three elements: a detailed description of processes, control mechanisms and corrective measures. It relies on an information system and must be applied to all steps of blood transfusion. PMID- 7881593 TI - Current issues in platelet transfusion therapy. PMID- 7881594 TI - Quality of platelet components: the role of suspension medium and leukocyte depletion. PMID- 7881595 TI - [Concentration of platelets from apheresis: methods of preparation]. AB - Apheresis platelet concentrates are platelet suspension obtained by apheresis from a blood cell separator. These techniques are now 20 years old. They are best way to collect great quantities of platelets from only one donor. These blood cell separators (discontinuous or continuous flow), realise extracorporeal circuit in which the blood in mixed with an anticoagulant (mainly citrate). All the procedures used are automatic and adapted with the donor parameters. The platelet donor is between 18 and 60 years old and can give 5 times per year. The platelet concentration in the product is divided into 3 classes (1 = 2 - 4 x 10(11) - 2 = 4 - 6 x 10(11) - 3 > 6 x 10(11)). Each category has a special price. Actually, we can store these platelets only 5 days. In the future, we need new studies and new directions (additive solution, new plastic) to propose a better viability and a longer storage. PMID- 7881596 TI - Some musings on the physician-God syndrome. PMID- 7881597 TI - Rural physician retention and workload: a moving target. PMID- 7881598 TI - Rural physician retention and workload: a moving target. PMID- 7881599 TI - Rural physician retention and workload: a moving target. PMID- 7881600 TI - Herpes simplex virus infection in family practice. Epidemiology 101. PMID- 7881601 TI - Mental diagnoses in primary care. The next generation. PMID- 7881602 TI - Development and validation of the SDDS-PC screen for multiple mental disorders in primary care. AB - OBJECTIVE: To develop, validate, and cross-validate a patient-completed screen for multiple mental disorders in primary care. DESIGN: Comparison of a patient self-report screen with an independent diagnostic assessment by mental health professionals using the Structured Clinical Interview for DSM-III-R diagnoses as criterion standard. SETTING: Three Rhode Island family practices and a South Carolina family medicine residency. SUBJECTS: In the initial validation study, 937 patients in Rhode Island were screened; 388 were interviewed. In the cross validation study, 775 patients were screened in Rhode Island and South Carolina, and 257 were interviewed. SCREEN ITEMS: Sixty-two questions pertaining to nine mental disorders and suicidal ideation. RESULTS: A 16-item screen remained after analysis of item and scale performance. Sensitivity, specificity, and positive predictive value, respectively, were calculated for the following scales: alcohol abuse or dependence (62%, 98%, and 54%), generalized anxiety disorder (90%, 54%, and 5%), major depression (90%, 77%, and 40%), obsessive-compulsive disorder (65%, 73%, and 5%), panic disorder (78%, 80%, and 21%), and suicidal ideation (43%, 91%, and 51%). Replication in a new sample showed attenuated but acceptable operating characteristics for cross-validation. CONCLUSIONS: The Symptom-Driven Diagnostic System for Primary Care screen assesses multiple mental disorders that are common to primary care. It serves as a sensitive, valid, and patient-friendly first step in a new approach to recognizing and managing mental disorders in primary care. Finally, it aids the primary care clinician in selecting an appropriate diagnostic interview module for the disease for which the patient screened positive. PMID- 7881603 TI - Brief diagnostic interviews (SDDS-PC) for multiple mental disorders in primary care. A pilot study. AB - OBJECTIVE: To pilot test the feasibility and validity of new, brief, structured, physician-administered diagnostic interviews for six mental disorders in primary care patients identified from a patient-completed screen. DESIGN: Comparison of the new diagnostic interviews with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, version P (SCID-P), administered independently by a mental health professional. SETTING: Three Rhode Island family practices and a South Carolina family medicine residency. SUBJECTS: Consecutive patients of either sex, aged 18 to 70 years, who were able to read and write English were eligible for screening; 775 patients completed the screen. Of these, 246 screened positive for at least one disorder and received at least one module. Of these, 158 received a SCID-P interview. RESULTS: The diagnostic interviews were found useful by all 16 participating physicians. Eighty-seven percent reported that they diagnosed a new mental problem, and 93% said that the modules clarified suspected symptoms. However, 26% thought the procedure was too time consuming, and 80% believed that reimbursement would be necessary for routine use. Detection of cases using the diagnostic modules was associated with physician intervention and with independent assessment of patient impairment. Over three quarters of the patients (76.4%) who were classified as positive by the physician interview for any of the diagnoses also tested positive on the SCID-P. Two thirds of the patients (62.7%) with at least one of the disorders (according to SCID-P) were classified by the physician interview as having a mental disorder. However, the operating characteristics varied across specific disorders and indicated a need for revisions and testing in larger samples. CONCLUSIONS: These brief physician-administered diagnostic interview modules are part of a screening and diagnostic system (Symptom-Driven Diagnostic System for Primary Care [SDDS-PC], The UpJohn Co, Kalamazoo, Mich) to detect mental disorders in primary care patients. The pilot results help establish their feasibility and validity. PMID- 7881604 TI - Seroprevalence of herpes simplex virus infections in a family medicine clinic. AB - OBJECTIVES: To determine the prevalence of herpes simplex virus (HSV) antibody in a general medical practice setting and to assess the frequency of subclinical infection. DESIGN: Prevalence study. SETTING: A family practice clinic at the University of Washington Medical Center, Seattle. PARTICIPANTS: Five hundred randomly selected patients between the ages of 18 and 45 years. MAIN OUTCOME MEASURES: Serum samples were tested by Western blot assay to detect the presence of antibody to HSV type 1 (HSV-1) and HSV-2. Demographic information and clinical history of oral and genital herpes were obtained. RESULTS: One hundred fourteen patients (23%) were seropositive for HSV-2 antibody, 277 patients (56%) were seropositive for HSV-1 antibody, 59 patients (12%) were seropositive for both HSV 2 and HSV-1 antibodies, and 163 patients (33%) were seronegative for both. Women were almost twice as likely as men to be seropositive for HSV-2 antibody (28% vs 15%, P < .001). Blacks had the highest rates of HSV-2 antibody seropositivity (60%) compared with whites (20%) and Asians (6%) (P < .001). Other demographic correlates of seropositivity included being older, having fewer years of education, and having public insurance. The specificity of a clinical history of genital herpes or sores for HSV-2 infection was high (99%), but the sensitivity was low (27%). CONCLUSIONS: Herpes simplex virus infection is common among patients seeking primary care. Women, blacks, and patients of lower socioeconomic status are most likely to be seropositive for HSV-2 antibody. The high frequency of unrecognized HSV infection has implications for primary care physicians in counseling patients regarding HSV infection and transmission. PMID- 7881605 TI - Does grandma need condoms? Condom use among women in a family practice setting. AB - OBJECTIVE: To examine the relationship between age and condom use among women who are typically seen in the primary care setting. DESIGN: Survey of a population using a self-administered questionnaire. SETTING: Four community-based family practice clinics located in a low-income, racially mixed geographical area. PATIENTS: All consenting patients (N = 995) during their visits for routine Papanicolaou tests. The mean age of patients was 35 years, with a range of 75 years (12 to 87 years). Respondents were predominantly black (63.2%), 39.2% were single, and over 65% had incomes no greater than $15,000/y. MAIN OUTCOME MEASURE: The outcome measure of condom use is reported. Data analysis of patients' sexual behavior revealed that older women might be at risk for sexually transmitted diseases (STDs). The hypothesis that condom use is related to age emerged during data collection. RESULTS: Condom use is related to being younger (< 31 years), having had an STD, having a sexual partner in whom an STD was diagnosed, having a lower income, or being single or black. In multivariate models, marital status (single), age (< 31 years), and having a partner with an STD remain significant. Among unmarried women, the effects of age, race, and a partner with STD remain, and being a nonsmoker is also significant. In the multivariate analysis for unmarried women, only age (< 31 years) is significantly related to condom use. An independent random sample of charts revealed that almost 45% of the patients aged 45 years or younger received condom counseling, whereas condoms were discussed with none of those older than 45 years. CONCLUSIONS: Because older patients (those beyond child-bearing years) are less likely to use condoms and evidently receive little education about condom use, older patients must be educated about the need for condoms. PMID- 7881606 TI - Attention-deficit hyperactivity disorder. Management by family physicians. AB - OBJECTIVE: To assess the evaluation and treatment practices of family physicians in regard to attention-deficit hyperactivity disorder (ADHD). DESIGN, SETTING, AND PARTICIPANTS: A 20-item survey was developed and mailed to all 940 family and general physicians in Kansas. MAIN OUTCOME MEASURES: Physician practices regarding ADHD. RESULTS: The 471 respondents (50.1%) included 386 physicians in private clinical practice, who constituted the study group. Ninety-eight percent of these physicians regularly saw children and over half suspected four or more cases of ADHD in the past year. When suspecting ADHD, 43% of the physicians referred for diagnosis and treatment; 30% evaluated and treated by themselves; and 27% referred for evaluation but did follow-up treatment themselves. There was no significant difference in these ratios between rural and urban physicians. Family physicians referred to a pediatric psychiatrist most often, with no apparent difference in referral pattern by community size; 75% indicated they were comfortable with their current referral support. Of the physicians who diagnosed and treated ADHD themselves, only 30.6% routinely ordered laboratory work or other tests, only 28.7% used teacher questionnaires, and only 20.4% used parent questionnaires. CONCLUSIONS: An important amount of patient care for ADHD is managed by family physicians, without significant differences between rural and urban practices. Most family physicians are satisfied with their current level of referral support. Physicians who treat ADHD themselves usually rely on clinical evaluation rather than special tests or standardized questionnaires. PMID- 7881607 TI - Usual care and outcomes in patients with sinus complaints and normal results of sinus roentgenography. AB - OBJECTIVE: To describe the usual care and outcomes of patients with sinus symptoms and normal sinus roentgenograms. DESIGN: Prospective cohort with 60-day follow-up. SETTING: Medical outpatient clinics at a university-affiliated Veterans Affairs medical center. PATIENTS: Consecutive patients (n = 126, 88% follow-up rate) with rhinorrhea (88%), facial pain (65%), or self-suspected sinusitis (24%) and normal four-view sinus roentgenography (median age, 47 years; 90% male; 56% white). MAIN OUTCOME MEASURE: Fourteen-day self-reported symptom status. RESULTS: Sixteen history and five physical examination items were recorded by clinicians who were blinded to the results of sinus roentgenography; clinical diagnoses and treatment plans were formulated by clinicians with knowledge of the results of sinus roentgenography. Clinical diagnoses included allergic rhinitis (27%), sinusitis (22%), viral respiratory tract infection (14%), and bronchitis (11%). Treatments included administration of antibiotics (40%), decongestants (32%), antihistamines (25%), and nasal steroids (9%). Forty nine percent achieved 14-day clinical success (13.5% were cured and 36% were much improved). Improvement was more likely among patients who presented with cough (odds ratio, 3.0; 95% confidence interval, 1.3 to 6.9) but was less likely among those with itchy eyes (odds ratio, 0.18; 95% confidence interval, 0.07 to 0.43). Patients with cough and without itchy eyes had significantly shorter clinical courses (P = .003). Of patients who achieved clinical success on day 14, 30% relapsed or recurred by day 60. CONCLUSION: With usual medical care, the syndrome of sinus symptoms and normal results of sinus roentgenography persists for at least 14 days in many patients; however, patients with cough but without itchy eyes may have shorter clinical courses. PMID- 7881608 TI - Perceived family stress as a predictor of health-related outcomes. AB - OBJECTIVE: To measure the predictive effect of patient-perceived family stress for health-related outcomes. DESIGN: Prospective study of patients whose social stress and support were measured by self-report at baseline with the Duke Social Support and Stress Scale and used as predictors of outcomes during an 18-month follow-up period. SETTING: Rural primary care community health clinic. PATIENTS: Convenience sample of ambulatory adults. INTERVENTION: None. MAIN OUTCOME MEASURES: Follow-up (one or more follow-up visits), frequent follow-up (more than six visits), referral and/or hospitalization (one or more), high follow-up severity of illness (upper-tertile mean Duke Severity of Illness Checklist scores), and high follow-up total charges (> or = $268). RESULTS: There were 413 patients with a mean age of 40.4 years. Of these, 58.6% were women; 47.2%, African American; 52.8%, white; 56.7%, married; 77.2%, wage earners or housekeepers; and 52.3% had more than one health problem. At baseline, patients with high self-reported family stress (upper-tertile Duke Social Support and Stress Scale scores) had lower quality of life, functional health, and social support scores and higher dysfunctional health and social stress scores than other patients. High baseline family stress scores (scale of 0 to 100) predicted follow-up (odds ratio [OR] = 1.014), frequent follow-up (OR = 1.021), referral and/or hospitalization (OR = 1.018), high severity of illness at follow-up (OR = 1.016), and high follow-up charges (OR = 1.018) after controlling for the effects of social support, age, gender, and race. Family stress scores were stronger predictors of these outcomes than the other social stress and support variables. CONCLUSION: The finding of patient-perceived family stress as a risk factor for unfavorable health-related outcomes suggests the need for early detection and treatment of family stress by family physicians. PMID- 7881609 TI - Can patients sexually harass their physicians? AB - It is the fate of certain fashionable legal terms that capture the attention of the media to have their usage expanded beyond the contexts for which they were originally designed. Such is the case with the term sexual harassment. Essentially, it describes situations in which a powerful person attempts to influence an individual's economic or academic status based on his or her response to sexual comments or behaviors. Title VII and Title IX of the US Code contain federal laws that prohibit discrimination based on sex in the workplace and in the education system, respectively. Accordingly, sexual harassment that occurs within the context of the employment or academic arena is prohibited under Title VII and Title IX and has evolved to apply to hostile work or academic environments that do not per se influence an individual's economic or academic status. PMID- 7881610 TI - Safe discontinuation of antihypertensive therapy. AB - We summarize herein the clinical and pathophysiological features of antihypertensive withdrawal syndrome and its risk factors, management, and prevention. Antihypertensive withdrawal syndrome occurs most frequently with beta blocking agents and centrally acting antihypertensives such as clonidine hydrochloride. This syndrome resembles a state of sympathetic nervous system hyperactivity. In the most critical case, it can be severe and life threatening. Antihypertensive dosages, particularly for beta-blockers and clonidine, should be tapered slowly rather than discontinued abruptly. PMID- 7881611 TI - The 'maternal grimace' sign. A clue to the importance of the contextual diagnosis. AB - Parents sometimes present illness in a child as an expression of their own distress, and patient-centered medicine attempts to address the underlying causes of problems by incorporating psychosocial factors in the diagnosis. However, in the real world of busy primary care, it is not always possible or appropriate to broaden every consultation, and the clinician may have to rely on certain clues that suggest the importance of exploring hidden reasons for consulting. Two cases are presented in which a mother's dramatic grimace during the gentle examination of a comfortable child alerted the clinician to parental anxiety disproportionate to the child's illness. Addressing parental anxiety proved fruitful. This "maternal grimace sign," pointing to the importance of the contextual diagnosis, underlines the usefulness of careful observation of all those involved in the consultation and may have implications for the way clinicians choose to position children and parents during physical examinations. PMID- 7881612 TI - Challenging times for the vascular laboratory. PMID- 7881613 TI - Physicians in the vascular diagnostic laboratory: educational background, prerequisite skills, credentialing, and continuing medical education. PMID- 7881614 TI - Training vascular surgery residents in the noninvasive vascular laboratory. PMID- 7881615 TI - Training and certification of the vascular technologist. PMID- 7881616 TI - Data management in the vascular laboratory. AB - As the clinical workload in the vascular laboratory increases and as the demand for additional documentation by hospital oversight committees and outside agencies grow, the need for computerized data management will become obvious. Although there are no generic, broadly applicable software programs to automate the laboratory's operations, applications can easily be developed using any of the current database programs to meet the needs of most laboratories. Fortunately, the intense competition in the microcomputer industry has recently made very powerful systems that are capable of providing the necessary computing support increasingly affordable. Such systems can be very simple or incredibly complex depending on the available local expertise and each laboratory's specific needs. In addition to facilitating the laboratory's daily operations, such a system will inevitably expedite the implementation of the laboratory's quality assurance program and will maximize utilization of existing personnel. This type of cost-effective solution to the ever-increasing demand for service will become increasingly important in maintaining the laboratory's fiscal viability. Although the prospects of undertaking such a task might seem daunting, especially to the computer novice, it is important to begin. Keep the system simple, at first, and allow it to develop as local expertise and confidence develop. The only prospect more frightening that sitting down to develop a computerized system for managing the laboratory's data, is the prospect of trying to continue without one! PMID- 7881617 TI - Quality assurance in the vascular laboratory. PMID- 7881618 TI - Indications for and frequency of noninvasive testing. PMID- 7881619 TI - Will the vascular laboratory remain economically viable? Impact of the RBRVS payment system. PMID- 7881620 TI - Cost-effectiveness of noninvasive surveillance after arterial surgery. PMID- 7881621 TI - Accreditation of vascular laboratories. PMID- 7881622 TI - Characterization of a newly established human gallbladder carcinoma cell line. PMID- 7881623 TI - Matrix and laminin synthesis in MDCK cells in vitro. PMID- 7881624 TI - Primary culture of human labial salivary gland acini. PMID- 7881626 TI - lrp130 gene assigned to chromosome 2. PMID- 7881625 TI - Corticotropin releasing factor inhibits proliferation of AtT-20 cells. PMID- 7881627 TI - Rapid induction of keratinocyte growth factor (FGF-7) and beta-actin after exposure of prostate stromal cells to androgen. PMID- 7881628 TI - Coculture of human articular chondrocytes with peripheral blood mononuclear cells as a model to study cytokine-mediated interactions between inflammatory cells and target cells in the rheumatoid joint. AB - A model for the coculture of chondrocytes in gelified agarose with mononuclear cells was developed to serve as an in vitro equivalent for cytokine-mediated events at the cartilage-synovial pannus junction in destructive arthropathies. Chondrocytes cultured in agarose keep their phenotypic stability. They release cartilage-specific aggrecans into the surrounding artificial matrix. When activated with lipopolysaccharide for 1 h, mononuclear cells release Interleukin 1 beta and Tumor Necrosis Factor alpha, thereby stimulating the chondrocytes to produce Interleukin 6, to diminish incorporation of 35S into aggrecans, and to degrade these intercellular macromolecules. This coculture model is a useful tool for studying interactions between inflammatory cells and target cells. To demonstrate its usefulness, the effect of three anti-inflammatory drugs (piroxicam, sulphasalazine, and hydrocortisone) on cytokine release by mononuclear cells, and subsequently on chondrocyte aggrecan metabolism was studied. The drugs were unable to abrogate Interleukin 1 and Tumor Necrosis Factor alpha release by activated mononuclear cells. Therefore, these pharmacological agents did not protect the artificial target tissue against cytokine-mediated degradation. PMID- 7881629 TI - Alkaline phosphatase and peptidase activities in Caco-2 cells: differential response to triiodothyronine. AB - Caco-2 cell human colon adenocarcinoma cell line was used to study the hormonal regulation of small intestinal epithelial cell differentiation. We had previously shown that insulin-transferrin-selenium and triiodothyronine (5 x 10(-8) M) supplemented medium can best replace serum after 2 days of culture for both the maintenance and differentiation of Caco-2 cells. The present study demonstrates that precoating petri dishes with complete serum allows the growth and differentiation of Caco-2 cells seeded directly in serum-free medium. On the other hand, precoating with dialyzed serum inhibits alkaline phosphatase and dipeptidyl-dipeptidase IV activities by more than 50%. The results obtained with complete serum-precoated culture plates indicate that there is no synergy between insulin and triiodothyronine because cells maintained in transferrin-selenium and triiodothyronine-supplemented medium, with or without insulin, express comparable enzyme activities. Moreover, large increases in alkaline phosphatase and dipeptidyl-dipeptidase IV activities were observed when triiodothyronine was added to the culture medium by the time confluency was reached. In contrast, gamma-glutamyltransferase was lowered to a greater extent when triiodothyronine was present from the beginning of culture. These findings show that triiodothyronine preferentially stimulates alkaline phosphatase and dipeptidyl dipeptidase IV activities during the differentiation period whereas it selectively inhibits gamma-glutamyltransferase during the proliferation phase. Triiodothyronine acts in a dose-dependent manner. PMID- 7881630 TI - A novel pathway for retinoic acid-induced differentiation of F9 cells that is distinct from receptor-mediated trans-activation. AB - Retinoic acid (RA) has striking effects on vertebrate development and induces differentiation of several lines of cells including embryonal carcinoma F9 cells. It is generally accepted that the actions of RA are mediated by nuclear receptors for RA. However, we now provide evidence that F9 cells can differentiate in response to RA without trans-activation by nuclear receptors. Irreversible differentiation of F9 cells was induced by 18 h of exposure to RA with subsequent incubation in the absence of RA. This induction of differentiation was not blocked after inhibition of protein synthesis and mRNA synthesis during the 18-h treatment with RA, but the endogenous RA receptors failed to activate transcription from their target genes that contain the receptor-binding sequences. During the commitment to RA-induced differentiation, at least five sets of four phosphorylated proteins underwent changes in the absence of protein synthesis de novo. These results suggest that there is a novel pathway for the action of RA that is independent of nuclear receptor-mediated trans-activation. PMID- 7881631 TI - Estradiol-17 beta stimulates proliferation of uterine epithelial cells cultured with stromal cells but not cultured separately. AB - There is indirect evidence that the in vivo proliferative response of rodent uterine epithelium to estrogen requires interaction with the underlying stroma in pre- and post-pubescent animals. To examine this potential requirement directly, the proliferative response of epithelium to 17 beta-estradiol in the presence or absence of stroma was measured in vitro. Uterine epithelial and stromal cells were isolated separately from immature or adult mice, and were maintained as monocultures or cocultures in defined, serum-free medium with or without 8 x 10( 9) M 17 beta-estradiol. Incorporation of bromodeoxyuridine into the DNA was determined by immunolabeling to assay proliferation in individual cells. Cell morphology and immunolabeling of cytokeratin were used to distinguish epithelial from stromal cells. Treatment of cocultures with 17 beta-estradiol for 24 h increased the proliferation of epithelial cells relative to controls approximately threefold, whereas, in monocultures of epithelial or stromal cells 17 beta-estradiol decreased the number of bromodeoxyuridine-incorporating cells by approximately half. Furthermore, cell contact between epithelial and stromal cells was important for the effects of 17 beta-estradiol on cells in cocultures. Approximately three quarters of the 17 beta-estradiol-induced proliferation of epithelial cells in cocultures was produced by epithelial cells within colonies that were also contacting stromal cells. These results are consistent with the hypothesis that stromal cells mediate the estrogenic proliferative response, and provide evidence that this mediation involves cell contact or stroma-mediated changes in the microenvironment immediately around the epithelial cell. PMID- 7881632 TI - Inositolhexakisphosphate (InsP6): an antagonist of fibroblast growth factor receptor binding and activity. AB - Fibroblast growth factors (FGF), which have been implicated in tumor cell growth and angiogenesis, have biological activities that appear to be mediated by both heparinlike extracellular matrix sites and transmembrane tyrosine kinase receptor sites. In the present study, we demonstrated that inositolhexakisphosphate (InsP6) inhibits basic FGF (bFGF) binding to heparin. Our spectrofluorometric analyses demonstrated that InsP6 not only bound to bFGF, presumably within the bFGF heparin-binding domain, but also protected bFGF from degradation by trypsin. Also, InsP6 inhibited the cellular binding of bFGF and other fibroblast growth factor family members such as acidic FGF (aFGF) and K-FGF in a saturable and dose dependent manner. Furthermore, concentrations as low as 100 microM InsP6 inhibited bFGF-induced DNA synthesis in AKR-2B fibroblasts, as well as the growth of bFGF- and K-FGF-transfected NIH/3T3 cells. Together, these results indicate that InsP6 may serve as a useful antagonist of FGF activity. PMID- 7881633 TI - Measurement of gap junctional communication by fluorescence activated cell sorting. AB - Cell-to-cell communication via gap junctions has played a fundamental role in the orderly development of multicellular organisms. Current methods for measuring this function apply mostly to homotypic cell populations. The newly introduced Fluorescence Activated Cell Sorting (FACS) method, albeit with some limitations, is simple, reliable, and quantitative in measuring the dye transfer via gap junctions in both homotypic and heterotypic cell populations. In the homotypic setting, the result in dye transfer from the FACS method is comparable to the scrape-loading and microinjection methods. Using this FACS method, we observed a decline of cell-to-cell communication in transformed and cancer cells. We also observed a differential degree of communication between two heterotypic cell populations depending on the direction of dye transfer. PMID- 7881634 TI - Retroviral mediated gene transfer in megakaryocytic cell lines. AB - There have been no reports, to date, of successful introduction of foreign DNA into committed megakaryocyte precursor cells. We have successfully infected two megakaryocytic cell lines, one a committed cell line (CHRF-288-11) and the other a bipotential cell line (K562), with a retroviral vector containing the bacterial lacZ gene and a neomycin resistance marker. Modification of standard protocols was required for successful infection of the committed megakaryocyte cell line. Presence of the lacZ transgene was demonstrated at the molecular level by polymerase chain reaction (PCR), and its expression at the mRNA level by reverse transcriptase-PCR. Presence of the bacterial beta-galactosidase was demonstrated by both immunofluorescence and enzyme activity. Treatment of the CHRF-288-11 infected cells with phorbol esters, which induces megakaryocytic differentiation, increases expression of the lacZ transgene. The staining pattern of the lacZ reaction product was perinuclear and punctate in the CHRF-288-11 cells, whereas it was uniform throughout the cytoplasm of the K562 cells, suggesting different sorting mechanisms for bacterial beta-galactosidase in these two cell types. Overall, these results demonstrate the feasibility and provide a method for infecting cultured megakaryocytic cell lines with retroviral of vectors such that a molecular analysis of megakaryocyte differentiation can be accomplished. PMID- 7881635 TI - Enhanced interleukin-2 production in human tumor-infiltrating lymphocytes engineered by 3'-truncated interleukin-2 gene. AB - Tumor-infiltrating lymphocytes (TILs), T lymphocytes associated with solid tumors that can be grown with interleukin (IL)-2 in vitro, preferentially accumulate at tumor sites after adoptive transfer. Therefore, TILs can be considered for use as cellular vehicles in gene therapy. We transduced melanoma TILs with the IL-2 gene and clarified functional characteristics of the TIL transductants. TILs transduced with 3'-end-truncated IL-2 gene (480 bp) produced high amounts of IL-2 detected in supernatants when compared to TILs transduced with the native IL-2 gene containing 3'-end adenine-thymidine (AT)-rich sequences (650 bp). The level of IL-2 in supernatants was higher with the addition of anti-Tac antibody (Ab) to block the consumption of IL-2 by the TILs. These TILs could proliferate autonomously in the absence of exogenous IL-2, and the proliferation of TILs could be completely blocked by anti-IL-2 Ab or anti-IL-2 receptor Ab. Thus TILs transduced with IL-2 gene can proliferate through the autocrine loop. However, the expression of IL-2 from TILs transduced with the IL-2 gene was downregulated after 2 to 3 weeks of G418 selection. Our study indicates the feasibility of transduction and expression of a truncated 480-bp IL-2 gene into TILs and the possibility of employing adoptive immunotherapy protocols using TILs modified with this IL-2 gene. PMID- 7881636 TI - Enhanced immune responses and anti-tumor activity by baculovirus recombinant carcinoembryonic antigen (CEA) in mice primed with the recombinant vaccinia CEA. AB - Carcinoembryonic antigen (CEA), a glycosylated protein of Mr 180, is one of the most widely studied oncofetal antigens. A majority of gastrointestinal cancers as well as breast and non-small-cell lung carcinomas express CEA. CEA thus represents a potential target for immunotherapy of several carcinoma types. A recombinant vaccinia-CEA virus (rV-CEA) was previously shown to induce anti-tumor activity in an experimental murine model after three rV-CEA inoculations. However, because the majority of cancer patients have received a previous smallpox vaccination, a long-lasting immune memory and/or induced anamnestic responses against vaccinia proteins may prevent repetitive boosting with the recombinant vaccinia virus expressing CEA. Therefore, other types of vaccines may be required to boost the anti-CEA immune response; one such schema would be the use of purified CEA as a boost in hosts given one administration of rV-CEA. Commercially available sources of CEA are usually derived from liver metastases extracts and are sometimes contaminated with nonspecific cross-reactive antigen. We have previously generated a recombinant source of full-length human CEA using a baculovirus expression system (bV-CEA). bV-CEA was shown to be glycosylated differently than native CEA, but it contains at least 10 epitopes found on native CEA (nCEA). Moreover, bV-CEA was able to induce a humoral response against CEA present on human colorectal cancer cell lines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881637 TI - Immunotherapy of a vaccinia colon oncolysate prepared with interleukin-2 gene encoded vaccinia virus and interferon-alpha increases the survival of mice bearing syngeneic colon adenocarcinoma. AB - Therapeutic effect of a vaccinia colon oncolysate prepared with interleukin-2 (IL 2) gene-encoded vaccinia virus (IL-2VCO) in combination with recombinant interferon-alpha (IFN-alpha) was studied in a syngeneic murine CC-36 colon hepatic metastasis model. Treatment with this IL-2VCO+IFN-alpha produced a higher survival rate (90% on day 60 after tumor transplantation) in mice having CC-36 hepatic metastases when compared to treatment with IFN-alpha (0%), VCO+IFN-alpha (0%), or IL-2VCO (11%). The only treatment that produced a survival rate similar to the survival rate of IL-2VCO+IFN-alpha was VCO+IL-2 + IFN-alpha (survival rate was 67%). The cause of the prolonged survival with the IL-2VCO+IFN-alpha treatment was identified as the reduction of CC-36 hepatic metastases (mean liver weight 1.31 g and mean tumor nodules 2). This reduction was significant when compared to IL-2VCO (1.58 g and 11), VCO+IFN-alpha (1.96 g and 53), and IFN-alpha (2.24 g and 91) treatments. The mechanism of the induction of antitumor response by the VCO+IL-2+IFN-alpha treatment was analyzed by measuring the direct cytotoxic activity of IFN-alpha on CC-36 tumor cells and by measuring the induction of cytolytic T-cell activity against CC-36 tumor cells. Results suggest that IFN-alpha produced minimal direct cytotoxic activity against CC-36 cells; however, the IL-2VCO+IFN-alpha combination therapy induced an enhanced cytolytic T-cell activity against CC-36 tumor cells (85.1% at E:T 100:1) when compared to other treatments (IL-2VCO 26.3%, VCO+IFN-alpha 13.4%, and IFN-alpha alone 6.3%). In addition, the role of T-cell subsets for the induction of antitumor immune response was analyzed in a survival study that used CD8-positive T cell-depleted mice. It was found that the survival rate was affected in mice depleted with CD8 positive T cells and treated with IL-2VCO+IFN-alpha when compared to control mice which had no T-cell depletion and were treated with IL-2VCO+IFN-alpha. This study suggests that the addition of IFN-alpha along with IL-2VCO increased the survival rate of mice having CC-36 hepatic metastases through the induction of CD8 positive T cells. Furthermore, this study confirms that IL-2VV can be used as a substitute for recombinant IL-2 in cytokine-augmented active specific immunotherapy. PMID- 7881638 TI - Inhibition of experimental hepatic metastasis by a monoclonal antibody that blocks tumor-hepatocyte interaction. AB - The role of tumor-hepatocyte interaction in carcinoma metastasis to the liver was investigated with use of the liver-metastatic murine carcinoma H-59 and a monoclonal antibody (MAb) C-11, which can inhibit tumor cell adhesion to hepatocytes in vitro by blocking a 64-71-kD glycoprotein receptor expressed on the tumor cell surface. The effect of this antibody on liver colonization by H-59 cells was analyzed. We found that treatment of H-59 cells with the antibody or with F(ab)2 fragments prior to tumor cell inoculation markedly and specifically reduced the ability of the cells to form hepatic metastases. An inhibitory effect was also seen when the antibodies were administered directly to tumor-inoculated mice. In contrast, no reduction was seen in the number of lung metastases when the antibody-treated cells were inoculated intravenously. Studies in vitro revealed that coculture of the tumor cells with hepatocytes had a stimulatory effect on tumor cell proliferation that could be specifically blocked by MAb C 11. The results suggest that H-59 cell adhesion to hepatocytes via the plasma membrane receptor promotes liver metastases formation and provide further evidence that biological reagents that can abrogate specific tumor-host cell interactions may be beneficial in the prevention of tumor cell dissemination. PMID- 7881639 TI - Phase II study of recombinant alpha-interferon and recombinant interleukin-2 metastatic breast cancer. AB - Ten patients with metastatic breast cancer were treated with a combination of recombinant alpha-interferon and recombinant interleukin-2. The toxicity of treatment was considerable, including one death on therapy. No objective responses were seen. PMID- 7881640 TI - High-dose interleukin-2 two days a week for metastatic renal cell carcinoma: a FNCLCC multicenter study. AB - The purpose of this study was to determine the efficacy and safety of a new high dose interleukin (IL)-2 regimen, given two days a week, for renal cell carcinoma. One hundred and four patients received IL-2 as a continuous i.v. infusion for 48 h at a daily dose of 24 x 10(6) IU/m2/day for 5 consecutive weeks. Patients were assessed for efficacy 4 and 8 weeks after the end of therapy, and patients who stabilized or responded received maintenance therapy with the same regimen. An objective clinical response was observed in 20 patients (complete in four, partial in 16). The dose of infused IL2 was significantly higher in the responders than in the nonresponders (p < 0.05). Clinical responses were significantly associated with a sedimentation rate of < 20 (p = 0.02), but no other prognostic factor was identified. Mean survival was 13 months. Grade 3 and 4 toxicities were rare, except for hypotension (58% of patients), the main dose limiting toxic effect. Overall, 83% of the planned dose of IL-2 was given. IL-2 given 2 days a week is active in metastatic renal cell carcinoma and well tolerated. PMID- 7881641 TI - Hats off to the Francis family. PMID- 7881643 TI - Is the routine use of inhaled beta-adrenergic agonists appropriate in asthma treatment? Yes. PMID- 7881642 TI - SP-A deficiency. A cause or consequence of inflammation in bronchopulmonary dysplasia? PMID- 7881644 TI - Is the routine use of inhaled beta-adrenergic agonists appropriate in asthma treatment? No. PMID- 7881645 TI - Continuous versus intermittent nebulized terbutaline: plasma levels and effects. AB - The purpose of this investigation was to compare continuous versus intermittent nebulization of a beta 2-agonist, terbutaline, to determine whether differences exist in plasma concentrations or adverse cardiovascular effects of the drug with these two techniques for its administration. Sixteen children 6 to 16 yr of age, admitted for acute asthma, were enrolled in this randomized double-blind clinical trial. Nebulization of 16 mg of terbutaline over an 8-h period was performed either continuously or intermittently, with a dose of 4 mg given over 20 min every 2 h. The peak plasma terbutaline concentration for the intermittent nebulization treatment (INT) group (5.1 +/- 2.1 ng/ml) occurred 1 h after the fourth inhalation treatment and was similar to the peak concentration for the continuous nebulization treatment (CNT) group, which was reached at the end of the 8 h period (4.7 +/- 2.3 ng/ml). The maximum heart rate increase for the INT group (19.6 +/- 18.3 bpm) occurred 1 h after the fourth dose and was similar to the peak observed in the CNT group (19.6 +/- 19.2 bpm), which occurred after 3 h. Similar increases in systolic and decreases in diastolic pressures were observed for the INT and CNT groups. No evidence of serious adverse myocardial complications was seen in either group, as evidenced by measurements of the MB fraction of creatine phosphokinase (CPK-MB) and Holter-monitor recordings. Continuous nebulization of the terbutaline produces similar plasma concentrations and cardiovascular physiologic responses as intermittent nebulization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881646 TI - Eosinophil viability-enhancing activity in sputum from patients with bronchial asthma, Contributions of interleukin-5 and granulocyte/macrophage colony stimulating factor. AB - To investigate the mechanisms of eosinophil activation in the airways of patients with asthma, we attempted to detect eosinophil-activating cytokines in sputum extracts obtained from asthmatic patients during acute attacks or in remission by eosinophil survival assay. Purified guinea pig eosinophils were cultured in the presence or absence of sputum extracts, and the eosinophil viability was measured on Day 4. Eosinophil viability in the presence of sputum extracts derived from patients during moderate or severe attacks was significantly higher than that for sputum obtained from patients in remission or during mild attacks or from those with other respiratory diseases, including bronchiectasis and diffuse panbronchiolitis (p < 0.05). The total symptom score during the week prior to sputum collection correlated with the eosinophil viability (rs = 0.79, p < 0.01). Eosinophil viability-enhancing activity (EVEA) in the sputum of asthmatic patients with moderate or severe attacks was neutralized by anti-IL-5 antibody and by anti-GM-CSF antibody by 19.9 +/- 13.7% and 76.9 +/- 8.2% (mean +/- SEM, n = 7), respectively. EVEA was completely neutralized by a combination of anti-IL-5 and anti-GM-CSF antibodies. There was a significant correlation between the concentration of eosinophil cationic protein (ECP) in sputum extracts and the eosinophil viability (rs = 0.54, p < 0.05). These findings suggest that IL-5 and GM-CSF are present in the sputum during asthma attacks and that these cytokines are at least partially responsible for eosinophil activation in asthma. PMID- 7881647 TI - Release of mast-cell-derived mediators after endobronchial adenosine challenge in asthma. AB - Preformed and newly generated mediators released from airway mast cells may play a role in adenosine-induced bronchoconstriction. To investigate the possible role of mast-cell-derived mediator release in mediating bronchoconstriction induced by adenosine 5'-monophosphate (AMP), we have examined the fluid obtained by bronchoalveolar lavage for inflammatory mediators and markers of airway permeability immediately after instillation of AMP directly into an airway segment of 10 asthmatic subjects. Eight subjects completed the protocol. When compared with the saline-challenged segment, the response to endobronchial stimulation with AMP was characterized by a prompt reduction in airway caliber paralleled by a significant rise in PGD2, histamine, and tryptase levels in the lavage fluid. After AMP challenge, the median (range) concentration for PGD2 increased from 36 to 205 pg/ml (p = 0.006), for histamine from 184 to 433 pg/ml (p = 0.018), and for tryptase from 0.30 to 0.54 ng/ml (p = 0.013). In addition, a small but significant rise in albumin levels (from 27.8 to 36.1 micrograms/ml; p = 0.031) was detected after endobronchial challenge with AMP. These findings indicate that adenosine-induced responses may be initiated by the acute release of mast-cell-derived mediators, including PGD2, histamine, and tryptase. PMID- 7881648 TI - Ciliary abnormalities in bronchial epithelium of smokers, ex-smokers, and nonsmokers. AB - Although respiratory changes induced by tobacco smoke have been extensively described, no study has focused on ciliary abnormalities associated with chronic smoking. Ciliary ultrastructure was studied in 37 adults with chronic sputum production (CSP) consisting of 13 current smokers (Group 1), 5 ex-smokers (Group 2), and 19 nonsmokers (Group 3). Five healthy nonsmokers constituted the control group (Group 4). Clinical and radiologic data and respiratory function tests were recorded. Acute respiratory infection was diagnosed by culture of tracheobronchial secretions obtained during bronchoscopy. Bronchial ciliated cells were obtained and processed for transmission electron microscopy. Within each group, the percentages of abnormal cilia were similar in patients with either chronic bronchitis or bronchiectasis and in patients with or without acute infection. The percentage of axonemal ultrastructural abnormalities (AUA) was higher in smokers (16.5% +/- 2.7%) and ex-smokers (17.5% +/- 7%) than in nonsmokers (5.2% +/- 1%) or control subjects (0.7% +/- 0.2%) (p < 0.0002). The AUA were polymorphic, characteristic of acquired ultrastructural changes. These results suggest that chronic smoking may induce an increased number of abnormal cilia which could participate in impairment of tracheobronchial clearance and which appears to be independent of the etiology of CSP. PMID- 7881649 TI - Responsiveness and variability of airflow obstruction in chronic obstructive pulmonary disease. Clinicopathologic correlative studies. AB - We have studied the relationships between pulmonary lesions and bronchodilator response and variability of FEV1 in 41 patients enrolled in the National Institutes of Health Intermittent Positive Pressure Breathing Trial who died, came to autopsy, and provided adequate tissue to quantitate lesions. The patients had moderate to severe chronic airflow obstruction and various degrees of response to 250 micrograms isoproterenol inhalation. Airway responsiveness was positively correlated with bronchial eosinophilia, bronchial inflammation, and bronchiolar fibrosis, and it was negatively correlated with bronchiolar goblet cell metaplasia and emphysema. Patients with an increase of 190 ml or more in FEV1 after bronchodilator had less bronchial cartilage and less goblet metaplasia in bronchioles. Airway smooth muscle was not related to airway responsiveness and variability. Flow rates were adversely affected by bronchial eosinophilia for given emphysema scores. This study shows the importance of the eosinophil as part of chronic nonspecific lung disease. Lack of airway responsiveness was associated with lesions such as emphysema and goblet cell metaplasia, which by themselves cause severe chronic airflow obstruction. The better-preserved lung function in patients with increased airway responsiveness is attributed to negative correlations with emphysema and positive correlations with bronchial eosinophilia. PMID- 7881650 TI - Environmental challenge studies in laboratory animal allergy. Effect of different airborne allergen concentrations. AB - In order to examine the dose-dependence of the airway response to animal allergens we performed environmental challenges on 17 workers with documented IgE mediated allergic reactions to laboratory rats. The 1-h environmental challenges were conducted in a vivarium during cage cleaning (high-allergen challenge), quiet sitting (low-allergen challenge), or in a remote location (sham challenge). During the high antigen conditions, mean Rat n 1 concentration was 166 +/- 28 ng/m3 compared with 9.6 +/- 3 ng/m3 in the low-allergen conditions. Nasal symptoms and nasal lavage mediator concentrations were significantly lower during the low-allergen conditions, but the pulmonary response was similar in terms of symptom scores, coughs, or FEV1 change. Using covariate analysis to examine the interaction of airborne allergen concentration, IgE-mediated sensitivity, and airway hyperresponsiveness, it could be shown that both upper and lower airway responses were strongly dependent on airborne allergen concentration but not on the degree of IgE sensitivity to rat allergen. We concluded that within sensitized workers, acute airway response is determined almost entirely by the intensity of environmental allergen exposure and the degree of bronchial hyperresponsiveness but not by the degree of IgE-mediated sensitivity. PMID- 7881651 TI - Prospective study of hospitalization for asthma. A preliminary risk factor model. AB - We conducted an exploratory analysis of several prospectively obtained objective measures of disease activity to derive a predictive model of hospitalization for asthma among 310 adults, ages 18 to 50 yr, with moderate to severe asthma. Baseline characteristics associated with increased risk of hospitalization in the succeeding year include (1) prior year hospitalization, (2) moderate or severe respiratory impairment, (3) a medication regimen consistent with severe asthma, (4) a history of significant systemic steroid use, (5) maximum overnight PEF variability > 40%, and (6) mean evening PEF < 60% of predicted (relative risk = 6.5, 6.9, 8.1, 3.7, 3.0, and 3.2, respectively). Recursive partitioning analysis, depicted as a "classification tree," provided a more sensitive (94%) and specific (68%) multivariate description of the data set than either logistic regression (87 and 48%, respectively) or a simple additive risk model (46 and 93%, respectively). Patients with very high (> 50%), moderately elevated (10 to 15%), and very low (< 5%) risk of hospitalization were identified on the basis of particular combinations of prior hospitalization history, level of respiratory impairment, and medication regimen. Overnight variability and mean evening PEF measured at home over a 2-wk period proved less informative for risk stratification than respiratory impairment determined once at baseline by office spirometry. The findings warrant replication and extension in other populations with the goal of developing decision rules for risk stratification and effective interventions for risk reduction. PMID- 7881652 TI - The influence of increased bronchial responsiveness, atopy, and serum IgE on decline in FEV1. A longitudinal study in the elderly. AB - We have performed a 4-yr prospective survey of the association of allergen skin test positivity, total serum immunoglobulin E (IgE), and bronchial responsiveness to methacholine, with longitudinal decline in FEV1, in subjects over 65 yr of age. In 1987, 324 subjects completed a respiratory questionnaire, and underwent measurement of FEV1 and FVC, methacholine challenge, skin prick testing (to Dermatophagoides pteronyssinus, cat fur, mixed grasses, and Aspergillus fumigatus) and estimation of total serum IgE. After an interval of 4 yr, 212 subjects were reexamined. The mean annual decline in FEV1 was significantly higher in males than in females, but was not significantly influenced by smoking habits defined at the start of the study. The relation of atopy (skin test reaction to allergen > or = 3 mm greater than saline control), increased bronchial responsiveness (PD20FEV1 < or = 6.4 mumoles methacholine) and serum IgE > 80 IU/ml, to annual decline in FEV1 was examined for each risk factor individually with adjustment for age, sex, height, and initial FEV1, by multiple linear regression. Both atopy and bronchial responsiveness were significantly associated with accelerated decline in FEV1. Elevated IgE was correlated with faster FEV1 decline in subjects who were current smokers at the start of the study. In a multiple regression model examining the mutually adjusted associations of all relevant variables with annual decline in FEV1, male sex was the most important predictor (B = 38.6 ml/yr, 95% Cl = 4.3, 72.9). Increased bronchial responsiveness also tended to be associated with accelerated decline in FEV1. In further analyses incorporating the same variables, but restricted to specific smoking categories, age was the only significant factor in the never smokers, whereas both atopy (B = 44.5 ml/yr, 95% Cl = 3.8, 85.3) and increased bronchial responsiveness (B = 43.5 ml/yr, 95% Cl = 4.6, 82.3) were significant predictors of accelerated FEV1 decline in former and current smokers combined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881653 TI - Longitudinal observations of serum IgE and skin prick test response. AB - The objective of the study was to assess skin prick test and IgE changes in a working population surveyed 5 yr apart and to determine whether age and smoking habits modify these changes. SPTs were performed on 223 subjects by the same method and common allergens (a mixture of grass pollens and a mixture of 95% house dust and 5% house dust mite). IgE measurements were done in duplicate by the same technique at each survey. A SPT-positive response at the first survey was highly predictive of a positive value at the second survey. The prevalence of positive SPT significantly increased in 5 yr (from 17.5 to 24.7%). A strong correlation was observed between IgE levels 5 yr apart (r = 0.92), and the IgE level appeared very stable. The initial IgE level was significantly greater among the converters than in consistently negative subjects (92.3 versus 30.1 IU/ml). Conversely, the initial IgE level was lower for the reverters than in consistently positive subjects (36.8 versus 97.0 IU/ml). In SPT negatives, non- and exsmokers had a greater decrease in IgE than current smokers (p = 0.06). IgE level appears to be a good predictor of SPT changes for both conversion and reversion. The IgE level appears very stable in midadulthood, which suggests that the adult environment may play a small effect in IgE level. PMID- 7881654 TI - Particulate air pollution as a predictor of mortality in a prospective study of U.S. adults. AB - Time-series, cross-sectional, and prospective cohort studies have observed associations between mortality and particulate air pollution but have been limited by ecologic design or small number of subjects or study areas. The present study evaluates effects of particulate air pollution on mortality using data from a large cohort drawn from many study areas. We linked ambient air pollution data from 151 U.S. metropolitan areas in 1980 with individual risk factor on 552,138 adults who resided in these areas when enrolled in a prospective study in 1982. Deaths were ascertained through December, 1989. Exposure to sulfate and fine particulate air pollution, which is primarily from fossil fuel combustion, was estimated from national data bases. The relationships of air pollution to all-cause, lung cancer, and cardiopulmonary mortality was examined using multivariate analysis which controlled for smoking, education, and other risk factors. Although small compared with cigarette smoking, an association between mortality and particulate air pollution was observed. Adjusted relative risk ratios (and 95% confidence intervals) of all-cause mortality for the most polluted areas compared with the least polluted equaled 1.15 (1.09 to 1.22) and 1.17 (1.09 to 1.26) when using sulfate and fine particulate measures respectively. Particulate air pollution was associated with cardiopulmonary and lung cancer mortality but not with mortality due to other causes. Increased mortality is associated with sulfate and fine particulate air pollution at levels commonly found in U.S. cities. The increase in risk is not attributable to tobacco smoking, although other unmeasured correlates of pollution cannot be excluded with certainty. PMID- 7881655 TI - Selection of spirometric measurements in a clinical trial, the Lung Health Study. AB - Although current recommendations for spirometry require that the largest value of FEV1 and FVC should be taken from the largest values of different maneuvers, the validity of this approach was recently questioned. It has been suggested that selection of the maneuver with the largest peak flow or the maneuver with the largest FVC should be used for measurement of spirometric indices. The present analysis was therefore undertaken to determine which method of selection of spirometric maneuvers would give the least short-term variability in a clinical trial population. We examined the spirometry test sessions from 5,885 individuals with mild to moderate chronic airflow obstruction who were screened at two visits 24.9 +/- 17.1 d apart for entry into a multi-center clinical trial, the Lung Health Study. We compared eight potential selection methods for FEV1 and FVC. Using these different selection methods, the coefficient of variation ranged from 4.1 to 4.9% for FEV1 and from 3.5 to 5.7% for FVC. The average absolute difference between the two test sessions ranged from 110 to 123 ml for FEV1 and from 149 to 200 ml for FVC. Although all of the methods gave good results, the mean of the three highest values and the largest single value from all maneuvers provided the least short-term variability for both FEV1 and FVC. We therefore conclude that there is no reason to change the currently recommended selection methods for FEV1 and FVC. PMID- 7881656 TI - The familial aggregation of obstructive sleep apnea. AB - An inherited basis for sleep-disordered breathing (SDB) has been suggested by reports of families with multiple affected members and by a previous study of the familial aggregation of symptoms of SDB. In this study, we quantify and characterize the aggregation of SDB and assess the degree to which familial similarities may be independent of obesity. This was a genetic-epidemiologic study that assessed the distribution of SDB in families identified through a proband with diagnosed sleep apnea and among families in the same community with no relative with known sleep apnea. SDB was assessed with overnight in-home monitoring of airflow, oxygen saturation, chest wall impedance, heart rate, and body movement. Standardized questionnaires were used to assess symptoms, and weight, height, and neck circumference were measured directly. Intergenerational and intragenerational correlation coefficients and pairwise odds ratios (ORs) were calculated with adjustment for proband sampling. In toto, 561 members of 91 families were studied: (1) 47 subjects with laboratory-confirmed SDB (index probands), (2) 44 community control subjects, and (3) the spouses and relatives of 1 and 2. Of all 91 families, 32 (35%) had two or more members with SDB, 30 (33%) had one affected member, and 29 had no affected members. SDB was more prevalent in the relatives of index probands (21%) than among neighborhood control subjects (12%) (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881657 TI - Assessment of the role of inheritance in sleep apnea syndrome. AB - Several reports have suggested a genetic importance in the pathogenesis of the sleep apnea syndrome (SAS). In this study, all adult (> 16 yr of age) offspring of 45 randomly selected parents with previously diagnosed SAS were asked to undergo a whole-night polysomnographic study. One hundred and five of 120 candidates participated in the study (66M:39F), with a high rate of compliance. Forty-seven percent of the offspring (36 males and 13 females; mean age, 32 yr) were found to have SAS. These results appear considerably higher (p < 0.001) than the common estimation of the prevalence of SAS in the population (4%). Another 21.9% of the offspring were "simple snorers" (17 males and 6 females; mean age, = 26 yr). Thirty-one percent were unaffected (13 males, 20 females; mean age, 29 yr). Only 16% of males over 35 yr of age were unaffected. In the single family studied in which both parents were affected, all three of their children (sons) had SAS: two grandsons older than 16 yr were simple snorers. Considering the well established prevalence of SAS in the general population (1 to 4%), these results may suggest that SAS is an inherited syndrome. PMID- 7881658 TI - Effects of dexfenfluramine on hypoxic pulmonary vasoconstriction and embolic pulmonary hypertension in dogs. AB - There has been suggestion of a possible relationship between the intake of the appetite suppressant dexfenfluramine and the development of primary pulmonary hypertension. We investigated the pulmonary vascular effects of acute intravenous dexfenfluramine in pentobarbital-anesthetized dogs ventilated in hyperoxia (fraction of inspired oxygen, FIO2, 0.4) and either challenged with a FIO2 of 0.1 to induce hypoxic pulmonary hypertension (n = 20) or given autologous blood clots to induce embolic pulmonary hypertension (n = 6). Pulmonary vascular tone was evaluated by multipoint (mean pulmonary artery pressure [Ppa] - pulmonary artery occluded pressure [Ppao])/cardiac output (Q) plots. Hypoxia increased Ppa - Ppao over the entire range of Q studied, from 1.5 to 4.0 L/min/m2, in 12 dogs (responders) and had no significant effect on (Ppa - Ppao)/Q plots in 8 other dogs (nonresponders). Dexfenfluramine did not affect (Ppa - Ppao)/Q plots in 6 responders but shifted (Ppa - Ppao)/Q plots to higher pressures in hypoxia in 6 nonresponders (p < 0.001). Dexfenfluramine had no effect on (Ppa - Ppao)/Q plots in the 6 dogs with embolic pulmonary hypertension. Because dexfenfluramine has serotoninergic properties, we compared the effects of ketanserin, a serotonin (5 hydroxytryptamine, 5-HT) S2 receptor antagonist, on naturally present versus dexfenfluramine-restored hypoxic pulmonary vasoconstriction. Ketanserin did not affect hyperoxic or hypoxic pulmonary vascular tone, neither in 6 responders nor in 2 nonresponders with dexfenfluramine-restored hypoxic vasoconstriction. We conclude that dexfenfluramine restores hypoxic pulmonary vasoconstriction in dogs with weak or absent hypoxic pressor response and that this effect is unlikely to be mediated by activation of 5-HT S2 receptors. PMID- 7881659 TI - Transient increase in interleukin-8 and pulmonary microvascular permeability following aortic surgery. AB - Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10( 3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1 antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881660 TI - Vascular reactivity in sepsis: importance of controls and role of nitric oxide. AB - We have previously reported differential impairment of pulmonary and systemic vascular contractility in hyperdynamic sepsis. The objectives of this study were (1) to determine whether the magnitude of this phenomenon depends on the control group chosen for comparison, and (2) to examine the role of nitric oxide (NO) in this altered vascular contractility. Rats were randomized to sepsis induced by cecal ligation and perforation (CLP) or to one of two control procedures. The Sepsis group had a jugular venous line for fluid administration, laparotomy, and CLP. Control group 1 (Control) had only a jugular venous line inserted, while group 2 (Sham) had a jugular venous line inserted and an abdominal incision. All rats were killed 24 h after surgery. Vascular contractility of small pulmonary arterial and thoracic aortic rings was assessed in vitro by obtaining cumulative dose-response curves to the contractile agonists potassium chloride (KCl), phenylephrine (PE), and prostaglandin F2 alpha (PGF2 alpha). Pulmonary vessels from animals in the Sepsis and Sham groups exhibited significant attenuation of the contractile responses to KCl, PE, and PGF2 alpha compared with the Control group. In contrast, contractility of the aortic rings to KCl, PE, and PGF2 alpha was not significantly different in the three groups studied. Incubation of pulmonary and aortic vessels with NG-nitro-L-argine methyl ester (L-NAME, 10 microM) caused an increase in the response to KCl, PE, and PGF2 alpha in pulmonary vessels in Sepsis and Sham rats but not in Control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881661 TI - Effect of synchronized, systolic, lower body, positive pressure on hemodynamics in human septic shock. A pilot study. AB - The pathophysiologic disturbance observed in volume-resuscitated patients with septic shock is primarily that of hyperdynamic circulation with a markedly reduced systemic vascular resistance. We hypothesized that external, mechanically applied, phasic lower body positive pressure could increase systemic vascular resistance and, thus, blood pressure in patients with refractory septic shock. A total of nine studies were performed on seven patients with septic shock refractory to volume resuscitation and vasopressors. All pre-existing therapies were continued unaltered during the study period. Phasic lower body positive pressure was produced by rapid synchronized inflation of pneumatic fabric cuffs fitted around each lower extremity. The cuffs were inflated for 200 ms to a pressure of 150 mm Hg, and the timing of inflation was adjusted to coincide with the peak systolic arterial pressure. Hemodynamic measurements were obtained at baseline and after 15 min of phasic lower body positive pressure. This off-on cycle was repeated twice for each study. Phasic lower body positive pressure increased mean arterial pressure by 12% and cardiac index by 14% (p = 0.01) over baseline (p < or = 0.001). Heart rate, central venous pressure, pulmonary capillary wedge pressure, arterial pH, arterial pO2, and mixed venous pO2 were unchanged. Synchronized external systolic compression of the lower extremities increased mean arterial pressure and cardiac output in seven patients with refractory septic shock. This hemodynamic improvement was independent of changes in calculated systemic vascular resistance. PMID- 7881662 TI - Effects of aerosolized prostacyclin in severe pneumonia. Impact of fibrosis. AB - The effects of aerosolized prostaglandin (PG) I2 on gas exchange and hemodynamics were investigated in patients ventilated mechanically because of severe community acquired pneumonia. Group A were patients without preexisting lung disease (n = 6), and Group B were those with underlying chronic fibrotic interstitial lung disease (n = 6). Ventilation-perfusion distribution was assessed by the multiple inert gas elimination technique. In Group A, low doses of aerosolized PGI2 (mean, 6.6 +/- 3.0 ng/kg/min) sufficed to decrease the mean pulmonary artery pressure (Ppa) from 35.0 +/- 1.5 to 31.0 +/- 1.6 mm Hg (p < 0.05), to improve the ratio of arterial oxygen to the fraction of inspired oxygen (PaO2/FIO2 increase from 100 +/- 18 to 134 +/- 18; p < 0.05), and to decrease intrapulmonary shunt (36.9 +/- 4.7 to 27.5 +/- 4.5%; p < 0.05). Systemic arterial pressure (Psa) and cardiac output remained unchanged. In Group B, aerosolized PGI2 was ineffective in doses less than 10 ng/kg/min. A dosage of 33.6 +/- 12 ng/kg/min reduced Ppa (38.0 +/- 2.4 to 30.8 +/- 2.1 mm Hg; p < 0.05), but it also decreased Psa (80.3 +/- 3.6 to 71.3 +/- 4.7 mm Hg; NS) and PaO2/FIO2 (73.8 +/- 6.6 to 65.5 +/- 6.8 mm Hg; p < 0.05) values and increased intrapulmonary shunt (44.7 +/- 3.0 to 49.4 +/- 5.0%, NS). After withdrawal of the PGI2 aerosol, all gas exchange and hemodynamic changes returned to preaerosol baseline values within 60 min in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881663 TI - Cardiorespiratory effects of volume- and pressure-controlled ventilation at various I/E ratios in an acute lung injury model. AB - Numerous approaches to the provision of mechanical ventilation during acute lung injury are currently available. Of these, pressure control inverse ratio ventilation has been considered superior to volume control ventilation with PEEP with respect to improving gas exchange and minimizing cardiovascular compromise. However, no study systematically compares volume-controlled (VC) and pressure controlled (PC) ventilation while maintaining mean airway pressure (MAP) constant at varying I/E ratios. We studied the effect of VC and PC with PEEP at normal (1:2) and inverse I/E ratios (2:1 and 4:1) on gas exchange, lung mechanics, and hemodynamics in a sheep lung injury model. Severe lung injury was induced in 12 sheep with bilateral lung lavages using normal saline; prelavage PO2 230 +/- 50 mm Hg, PEEP 5 cm H2O and postlavage, pretreatment PO2 70 +/- 20 mm Hg, PEEP 10 cm H2O, both at FIO2 0.50. MAP was kept constant throughout the study at 25 +/- 2 cm H2O while ventilating all animals with a VT of 10 ml/kg and a rate of 20/min by randomized application of VC and PC with I/E ratios of 1:2, 2:1, and 4:1. Despite liberal fluid administration, all ventilatory modes depressed cardiac output compared with preinjury values. However, gas exchange and hemodynamics did not differ among ventilation modes or I/E ratios.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881664 TI - Distribution of regional density and vascular permeability in the adult respiratory distress syndrome. AB - Although recent X-ray computed tomography (CT) data show that ventral-dorsal gradients in density are common in the adult respiratory distress syndrome (ARDS), we hypothesized that the ventral-dorsal gradient of pulmonary vascular permeability would be evenly distributed in patients with ARDS. We tested this hypothesis by analyzing previously reported data (Am Rev Respir Dis 1991; 143:150 154) obtained by the nuclear medicine imaging technique of positron emission tomography (PET). Measurements of regional lung density (LD), extravascular density (EVD), and the pulmonary transcapillary escape rate (PTCER; an index of vascular permeability) were obtained in eight patients with ARDS and in 10 normal subjects. The data from four contiguous tomographic slices were organized into 20 anatomically oriented "bins" from the ventral (Bin #1) to dorsal (Bin #20) position. Mean overall LD, ERD, and PTCER were all significantly higher (p < 0.05) in the ARDS patients than in normal subjects. Regression slopes of LD versus bin and EVD versus bin were significantly positive (ventral-to-dorsal) in seven of eight and six of eight ARDS patients, respectively. Mean PTCER values showed no difference between ventral and dorsal bin values. A significantly negative slope of PTCER versus bin was detected in five cases and a positive slope in 3, so that the group value was not significant. These data confirm that ventral-dorsal gradients in LD and EVD exist in patients with ARDS. In contrast, no consistent ventral-dorsal distribution of increased pulmonary vascular permeability is present. PMID- 7881665 TI - Inspiratory fall in systolic pressure in normal and asthmatic subjects. AB - We used a noninvasive monitor of arterial pressure to determine whether respiratory changes in arterial pressure were closely correlated with airflow obstruction in asthmatic patients during bronchial challenge with methacholine. To validate the noninvasive measurement of respiratory changes in arterial pressure, a preliminary study in 6 subjects with normal cardiovascular and respiratory systems was done during cardiac catheterization for suspected coronary artery disease. There were no significant differences between inspiratory falls in systolic pressure measured noninvasively and those measured from intraaortic pressure. In 11 otherwise healthy asthmatic patients we measured finger arterial pressure, end-expiratory lung volume (FRC), and forced expired volume (FEV1) during baseline and bronchial challenge in the supine posture. Finger arterial pressure was also measured in 11 normal control subjects seated and supine. Normal subjects had an inspiratory fall in systolic pressure (IFSP) of 3.2 mm Hg supine and 5.1 mm Hg seated (p < 0.01). Asthmatic patients when bronchodilated (seated FEV1 = 83 +/- 7% of predicted) had an IFSP of 5.9 mm Hg supine (p < 0.01 compared with supine normal subjects). During bronchial challenge (average fall in FEV1 = 22%), IFSP increased to 16.1 mm Hg (p < 0.001 compared with baseline). In asthmatic subjects, there was a significant correlation between IFSP and FEV1 (mean r = -0.92 +/- 0.05, p < 0.01), and the average change in IFSP/change in FEV1 was -0.38 mm Hg per percentage change in FEV1. During subsequent bronchodilation, IFSP decreased with a similar time course as relaxation of airway smooth muscle, assessed by the breath-to-breath fall in FRC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881666 TI - Effect of inspiratory flow rate on respiratory sensation and pattern of breathing. AB - We examined the effect of inspiratory flow rate (IFR) on respiratory sensation during mechanical ventilation in 10 normal subjects. We adjusted the ventilator tidal volume (VT), frequency, and IFR until subjects indicated that they were maximally comfortable ("comfort IFR"). Subjects then rated breathing discomfort on a visual analog scale (VAS) while IFR was varied among four levels: 70%, 100%, 200%, and 300% of the comfort IFR. When compared with VAS ratings at the comfort IFR (4.4 +/- 1.2, mean +/- SEM), VAS ratings were significantly greater at the lowest (i.e., 70% comfort; 12.1 +/- 2.1) and highest (300% comfort; 8.2 +/- 0.9) IFR; there was no difference in ratings between the comfort IFR and 200% comfort IFR. At the lowest IFR, the breathing discomfort arose in the chest and had an air hunger-like quality; at high IFR, the discomfort arose in the upper airway. In the second portion of the study, subjects used open magnitude estimation to rate breaths of five different sizes at three different IFR (70%, 100%, and 200% of comfort rate). Neither the exponent nor intercept for VT perception differed among the three IFR. Our results demonstrate that although IFR does not alter magnitude estimation of breath size, deviations of IFR from that desired by the subject may greatly affect respiratory comfort. PMID- 7881667 TI - Tissue factor pathway inhibitor and von Willebrand factor antigen levels in adult respiratory distress syndrome and in a primate model of sepsis. AB - Tissue factor pathway inhibitor (TFPI) is an anticoagulant protein primarily synthesized by the endothelium. A major fraction (approximately 85%) of TFPI remains associated with the endothelium, whereas a small fraction (approximately 15%) is secreted into the blood. In our attempts to search for a marker(s) of endothelial injury in the setting of adult respiratory distress syndrome (ARDS), we retrospectively measured plasma TFPI levels in patients at risk for and with ARDS caused by several etiologic factors. Plasma von Willebrand factor antigen (vWF-Ag), another endothelial-specific protein, was also measured in these patients. The mean plasma TFPI levels were slightly elevated (approximately 1.3 fold), whereas vWF-Ag levels were significantly elevated (approximately 3-fold) in the at-risk group as compared with those in the normal subjects. Both the TFPI (approximately 1.8-fold) and the vWF-Ag (approximately 4-fold) levels were further elevated in the ARDS group. Moreover, the sequential plasma samples from patients with ARDS had progressively increased levels of vWF-Ag and TFPI up to Days 4 and 8, respectively. Neither plasma vWF-Ag nor TFPI levels correlated with mortality in the at-risk group or the ARDS group. TFPI levels were also measured in bronchoalveolar lavage fluids (BALF). The levels (ng/ml) were: normal subjects, 0.05 +/- 0.02 SE; at-risk group, 0.35 +/- 0.16 SE; ARDS group, 0.99 +/- 0.28 SE. Thus, the BALF TFPI levels were increased approximately 7-fold in the at risk group and approximately 20-fold in the ARDS group relative to the value in the normal subjects. These findings indicate increased local synthesis of TFPI in the alveolar space both in the at-risk patients and in those with ARDS. In additional studies in a primate model of sepsis, lethal doses (LD100) of E. coli administered to baboons resulted in a progressive increase in TFPI levels (approximately 2-fold at 6 h), whereas sublethal doses caused only minimal increase (approximately 1.2-fold). The vWF-Ag levels were elevated approximately 5-fold after infusion of LD100 concentrations of E. coli at 6 h and 4-fold after infusion of sublethal concentrations of E. coli at 24 h. Autopsies on animals in the LD100 group revealed pulmonary congestion, leukocyte infiltration, edema, and hemorrhage, all suggestive of acute lung injury. Thus, in the setting of acute lung injury plasma vWF-Ag appears to be considerably increased prior to significant damage to the endothelium, whereas increased plasma TFPI occurs only after severe injury.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7881668 TI - Protective effects of N-acetylcysteine treatment after phosgene exposure in rabbits. AB - We examined the effects of treatment with N-acetylcysteine (NAC) on pulmonary edema formation in isolated perfused rabbit lungs following in vivo phosgene exposure. This study focused on posttreatment intratracheal administration of NAC after exposure. Rabbits, 2 to 3 kg, were exposed to a cumulative dose of phosgene to attain a concentration x time exposure effect of 1,500 ppm/min. Lungs were perfused with Krebs-Henseleit buffer at 40 ml/min from 70 to 150 min after exposure. Pulmonary artery pressure (Ppa), tracheal pressure (Pt), and the rate of lung weight gain (LWG) were measured continuously. Perfusate concentration of peptide leukotrienes LTC4, D4, and E4 were measured every 20 min during perfusion. At the conclusion of the experiment, lung tissue was analyzed for reduced and oxidized glutathione (GSH and GSSG) and lipid peroxidation (thiobarbituric acid-reactive substances, TBARS). Exposure to phosgene significantly increased Pt, LWG, LTC4, D4, and E4, TBARS, and GSSG over time compared with controls. Compared with phosgene, intratracheal NAC lowered Ppa, LWG, LTC4, D4, and E4, TBARS, and GSSG. We conclude that NAC protected against phosgene-induced lung injury by acting as an antioxidant by maintaining protective levels of glutathione, reducing both lipid peroxidation and production of arachidonic acid metabolites. PMID- 7881669 TI - N-acetylcysteine preserves oxygen consumption and gastric mucosal pH during hyperoxic ventilation. AB - Hyperoxic ventilation, used to prevent hypoxemia during potential periods of hypoventilation, has been reported to paradoxically decrease whole body oxygen consumption (VO2). Reduction in nutritive blood flow due to oxygen radical production is one possible mechanism. We investigated whether pretreatment with the sulfhydryl group donor and O2 radical scavenger N-acetylcysteine (NAC) would preserve whole body VO2 and prevent deterioration of oxygenation in gastric mucosal tissue during hyperoxia. Thirty-eight patients, requiring hemodynamic monitoring (radial and pulmonary artery catheters) due to sepsis syndrome, were included in this randomized experiment. All patients exhibited stable clinical conditions (hemodynamics, body temperature, hemoglobin, FIO2 < 0.5). A gastric tonometer was placed to measure the gastric intramucosal pH (pHi), which indirectly assesses nutritive blood flow to the mucosa. Cardiac output was determined by thermodilution and VO2 by cardiovascular Fick. After baseline measurements, patients randomly received either 150 mg.kg-1 NAC (n = 19) or placebo (n = 19) in 250 ml 5% dextrose intravenously over a period of 15 min. Measurements were repeated 30 min after starting NAC or placebo infusion, 30 min after starting hyperoxia (FIO2 = 1.0), and 60 min after resetting the original FIO2. There were no significant differences between groups in any of the measurements before treatment and after the return to baseline FIO2 at the end of the study. NAC, but not placebo infusion, caused a slight but significant increase in cardiac output and decrease in systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881670 TI - The early pattern of conjugated dienes in liver and lung after endotoxin exposure. AB - If lipid peroxidation (LP) contributes to organ dysfunction in sepsis rather than simply reflecting established injury, it should occur soon after the onset of the septic insult, and it may not progress uniformly in all organs. We assessed whether LP occurs within 90 min after onset of continuous intravenous endotoxin (E. coli 055:B5) infusion in rats, using second-derivative spectroscopy to semiquantitatively assess conjugated dienes (CD) in lung, liver, and plasma phospholipids. Measurements were also made after 90-min infusions with saline or 1 mM H2O2. Both the quantity and spectrophotometric patterns of CD differed between the three groups. Compared with saline controls, lung lipid CD increased after both H2O2 and endotoxin. Venous plasma CD were elevated only after H2O2, while arterial plasma and liver lipid CD were not different between the three groups. Exhaled ethane (an indicator of peroxidation of omega-3 fatty acids) did not differ between groups. Wet-to-dry lung weights were significantly increased after endotoxin compared with that after saline controls. Our results indicate that tissue-specific LP occurs within 90 min of endotoxin or H2O2 intravenous infusion. PMID- 7881671 TI - Failure of talc pleurodesis is associated with increased pleural fibrinolysis. AB - Diffuse pleural inflammation and fibrin deposition following the instillation of the sclerosing agent is considered necessary for a successful pleural symphysis. We hypothesized that an impairment in fibrin formation or an increased endopleural fibrinolysis would lead to failure of pleurodesis. To investigate changes in the pleural coagulation/fibrinolysis balance, we studied 75 consecutive patients who underwent thoracoscopy. Fifty-four of these patients with malignant pleural effusions and four with a benign recurrent effusion underwent thoracoscopic talc pleurodesis. Another four patients with malignancy and 13 with benign effusions had no talc poudrage performed and were included as a control group. Serial determinations of thrombin-antithrombin III complex (TAT), plasminogen activator inhibitor (PAI), and D-dimer were made in pleural fluid samples taken at the beginning of thoracoscopy (baseline), immediately after thoracoscopic biopsies had been done (postbiopsy), 3 h after thoracoscopy- either with talc poudrage or without--and 24 and 48 h after the procedure, as well as in cases of recurrence of effusions (farline). Successful pleurodesis was obtained in 42 of 52 patients who could be evaluated (81%), and failure was seen in 10. Strong activation of coagulation and production of PAI was observed in all groups, including the control (no talc) group. Fibrinolytic activity (as expressed by D-dimer levels) showed a clear decline 24 h after talc poudrage in patients with a good outcome of pleurodesis, as oppossed to those with bad results and to the control group, and returned to the baseline by 15 d. We conclude that increased pleural fibrinolytic activity is associated with failure of pleurodesis, despite significant inhibitory activity of PAI in all groups. PMID- 7881672 TI - Temporal evolution of pleural fibrosis induced by intrapleural minocycline injection. AB - Minocycline is as effective as tetracycline in inducing pleural fibrosis, but the long-term pleural changes induced by minocycline are unknown. The objective of this study was to evaluate in rabbits the evolution of the pleural changes induced by the intrapleural instillation of minocycline. Under light anesthesia, minocycline at 10 mg/kg in a total volume of 2 ml of bacteriostatic saline solution was injected into the right pleural space of 25 male rabbits. The animals were sacrificed in groups of five at 15 d and 1, 2, 4, and 6 mo. Macroscopic and microscopic examinations of the pleura were performed for evidence of pleural fibrosis and inflammation. Similarly, the underlying lung was also examined for microscopic alveolar fibrosis and inflammation. During the 6-mo observation period there was no significant change in the degree of pleural fibrosis. In contrast, microscopic pleural inflammation, alveolar fibrosis, and alveolar inflammation all decreased significantly over the observation period. In conclusion, intrapleural minocycline injection results in persistent pleural fibrosis at 6 mo. It remains to be determined whether the pleural fibrosis will persist beyond this period. PMID- 7881673 TI - Pneumocystis carinii pneumonia: a major complication of immunosuppressive therapy in patients with Wegener's granulomatosis. AB - The risk factors and clinical and laboratory parameters in Pneumocystis carinii pneumonia in patients with Wegener's granulomatosis have not been well characterized. We undertook a retrospective chart review of all patients with a diagnosis of Wegener's granulomatosis and P. carinii pneumonia who were followed at the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. The chart review focused on clinical, laboratory, and roentgenologic evidence of P. carinii pneumonia. Eleven cases of P. carinii pneumonia were diagnosed in some 180 patients with Wegener's granulomatosis, for an overall incidence of approximately 6%. All patients developed P. carinii pneumonia either during the initial course of treatment or during therapy for recurrent Wegener's granulomatosis. All patients were receiving daily glucocorticoids and a second immunosuppressive therapy. Lymphocytopenia was noted in all patients, with a mean +/- SEM total lymphocyte count of 303 +/- 69 cells/microL. All patients tested (10 of 11) were seronegative for human immunodeficiency virus (HIV) infection. Eight presented with worsening chest roentgenograms compared with baseline, whereas three presented with normal chest roentgenograms. We conclude that P. carinii is a common opportunistic pathogen in patients with Wegener's granulomatosis receiving immunosuppressive therapy. Therapeutic immunosuppression (daily glucocorticoids and immunosuppressive agents) and the resultant lymphocytopenia, as well as the lymphocyte and monocyte functional abnormalities caused by glucocorticoids, may be the most likely factors predisposing to P. carinii pneumonia in patients with Wegener's granulomatosis. Based on our data, all patients with Wegener's granulomatosis should be given chemoprophylaxis against P. carinii while they are receiving daily glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881674 TI - Ciliary disorientation in patients with chronic upper respiratory tract inflammation. AB - Random ciliary orientation was recently described as a possible variant of primary ciliary dyskinesia (PCD). The cilia have normal ultrastructure and nearly normal ciliary beat frequency (CBF) but lack efficacy because the beat direction is disoriented. However, delayed mucociliary clearance (MCC), transitory changes in ultrastructure, and slowed CBF can all occur in the presence of inflammation. This study investigated groups of patients with upper respiratory tract inflammation caused by infection to assess whether ciliary disorientation was present and its relation to MCC. The study population consisted of 10 healthy nonatopic nonsmoking volunteers, 15 patients with idiopathic bronchiectasis and chronic mucopurulent sinusitis, 12 patients with cystic fibrosis, and two patients with the clinical features of PCD but normal CBF and ciliary ulstrastructure. Ciliary disorientation was significantly (p < 0.05) increased in the three patient groups compared with the volunteers, being greatest in the two patients with the clinical features of PCD and in bronchiectasis patients with P. aeruginosa, and was positively correlated (r = 0.9) with MCC but not with CBF. Treatment of one patient with antibiotics and topical corticosteroids for a prolonged period resulted in ciliary disorientation returning to normal. Ciliary disorientation may therefore occur secondary to inflammation caused by infection, and the study suggests that ciliary disorientation rather than ultrastructural abnormalities or slow CBF results in delayed MCC. PMID- 7881675 TI - Two-stage tuberculin skin testing in individuals with human immunodeficiency virus infection. Community Programs for Clinical Research on AIDS. AB - In this study we estimated occurrence of the booster effect in a population infected with the human immunodeficiency virus (HIV) and assessed the relation between the booster effect, T-lymphocyte CD4 cell counts, tuberculosis risk categories, and HIV exposure categories. Patients were recruited from 13 participating sites of the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). A two-stage tuberculin skin test was applied to 709 HIV-infected patients using the Mantoux method. An induration reading < 5 mm on the first test and > or = 5 on the second skin test defined the booster effect. Overall, 18 patients, or 2.7% (95% confidence interval, 1.6 to 4.2) experienced the booster effect. Boosted responses were seen in eight (2.1%) anergic patients, six (4.5%) nonanergic patients, and four (2.5%) with anergy status unknown. Boosting was noted in 1 of the 131 women enrolled. Age, race, CD4 cell count, injection drug use, anergy status, tuberculosis risk categories, and HIV exposure categories were not predictive of boosting. The booster effect occurs in a small percentage of HIV-infected patients tested, thus identifying small numbers of patients with latent tuberculosis infection. The two-stage procedure is probably of limited value in the diagnosis of latent tuberculosis in HIV-infected persons. PMID- 7881676 TI - Allergen-induced airway inflammation in rats. Role of insulin. AB - Clinical asthma appears to be less severe when diabetes mellitus is superimposed. To examine whether insulin influences the development of allergic reactions in the airway mucosa antigen challenge, normal and diabetic rats sensitized against ovalbumin (OA) were used. Compared with controls, animals rendered diabetic by the injection of alloxan presented markedly decreased cell yields from bronchoalveolar lavage after OA challenge. The impaired response was not related to antibody production because enhanced IgE antibody titers of the same magnitude were found in both control and diabetic animals. Similarly, the mechanism underlying the inhibited responses could not be ascribed to hyperglycemia or intracellular glucopenia, first, because correction of blood glucose levels through fasting did not restore the decreased response, and second, because administration of 2-deoxyglucose, which blocks glucose utilization, did not affect the bronchoalveolar reaction to OA challenge in normal animals. Reversal of the impaired responses was attained by treatment of diabetic animals with insulin. There is evidence that insulin exerts proinflammatory effects. We conclude that insulin might modulate the inflammatory component of asthmatic responses. PMID- 7881677 TI - Role of VLA-4 and LFA-1 in allergen-induced airway hyperresponsiveness and lung inflammation in the rat. AB - The aim of the study was to evaluate the effects of blocking the integrins VLA-4 and LFA-1 on allergen-induced airway eosinophilia and responsiveness in Brown Norway rats. Ovalbumin-sensitized rats were exposed to either aerosols of ovalbumin or saline. Airway responsiveness to methacholine (MCh) was determined 8 and 32 h after challenge. Cellular populations in the lung lavage and lung tissues were determined 32 h after allergen challenge. Total numbers of eosinophils were increased in the lung lavage (25 ml) and the small airways/parenchyma in the ovalbumin (OA)-challenged rats (4.37 x 10(6) +/- 0.71 and 15.54 x 10(6) +/- 1.99, respectively) compared with the saline-challenged rats (0.99 x 10(6) +/- 0.81 and 4.84 x 10(6) +/- 2.27; p < 0.05). Animals treated with both anti-VLA-4 and anti-LFA-1 mAbs and with anti-LFA-1 mAb alone had reduced numbers of eosinophils in the lung lavage (0.76 x 10(6) +/- 0.80 and 0.40 x 10(6) +/- 1.14, respectively; p < 0.05) and in the small airways/parenchyma (8.64 x 10(6) +/- 2.07 and 4.44 x 10(6) +/- 3.20; p < 0.05). Anti-VLA-4 mAb treatment alone did not alter the eosinophils recovered from the lung. Airway responsiveness to methacholine increased from 8 to 32 h in all ovalbumin challenged rats, but treatment with anti-VLA-4, anti-LFA-1, or both mAbs prevented the increase in responsiveness. In conclusion, allergen-induced airway hyperresponsiveness is inhibitable by blocking either VLA-4 or LFA-1 integrins and is associated with a lung eosinophilia that is LFA-1 dependent and VLA-4 independent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881678 TI - Acetylcholine release from airway cholinergic nerves in horses with heaves, an airway obstructive disease. AB - The present study was conducted to determine if acetylcholine (ACh) release from airway cholinergic nerves is increased and if modulation of ACh release by prejunctional receptors is altered in horses with heaves, an obstructive airway disease characterized by airway inflammation and bronchospasm. Trachealis strips and bronchial segments of normal horses and horses affected with heaves were suspended in 2-ml tissue baths. ACh release was induced by electrical field stimulation and the bath ACh content was measured by high performance liquid chromatography (HPLC) with electrochemical detection. In response to electrical field stimulation, the rate of ACh release from cholinergic nerves innervating the trachea was not significantly different between the two groups of horses. The nonselective muscarinic receptor antagonist atropine augmented ACh release to the same extent in both groups, indicating that there is no dysfunction of muscarinic autoreceptors on cholinergic nerves of large airways from horses with heaves. Compared with the data from normal horses, the inhibitory effect of the alpha 2 adrenoceptor agonist clonidine on ACh release was lacking in the bronchi and less potent in the trachea, suggesting that the prejunctional alpha 2-adrenoceptors are dysfunctional in horses with heaves. Neither exogenous prostaglandin E2 (PGE2) nor the cyclooxygenase inhibitor indomethacin influenced ACh release from the bronchi, suggesting that a decrease in airway mucosal PGE2 production reported previously in horses with heaves does not alter ACh release. PMID- 7881679 TI - Increased maximal pulmonary response to methacholine and airway smooth muscle in immature compared with mature rabbits. AB - We compared the effect of maturation upon the maximal pulmonary response to inhaled methacholine in rabbits and also assessed whether there was an age related difference in the quantity of airway smooth muscle. In sedated, paralyzed, and mechanically ventilated rabbits, pulmonary resistance was measured following increasing doses of aerosolized methacholine (0.5 to 256 mg/ml). The six mature rabbits (6 mo) demonstrated a plateau in their dose-response curves whereas only three of six immature animals (1 mo) had a plateau. The immature compared with the mature animals had a greater maximal increase in pulmonary resistance (950% versus 380%). The lungs were examined by light microscopy to determine morphometrically the area of smooth muscle (ASM) in the airway walls. ASM was normalized for airway size by dividing by the ideal airway area. The normalized ASM was different for the two age groups and the immature animals' airways had more smooth muscle. The relationship between airway size and ASM was similar for the two age groups with smaller airways having proportionately more smooth muscle. The differences with age in ASM area were primarily due to the immature animals having a greater number of airways of small size. There was not a significant relationship between the maximal percent increase in pulmonary resistance and the normalized ASM. We conclude that inhaled methacholine produces a greater maximal increase in the pulmonary resistance of immature than mature rabbits and that this difference is unlikely to be caused by a proportionately greater quantity of ASM in the immature than the mature rabbit airways. PMID- 7881680 TI - Elevated urinary leukotriene E4 in chronic lung disease of extreme prematurity. AB - We determined if pulmonary peptidoleukotrienes contribute to the pathogenesis of chronic lung disease of extreme prematurity (CLD) by measuring urinary leukotriene E4 (uLTE4). Study patients had a birth weight < 1000 g and were about 28 d old when they were classified as normal control subjects (n = 8) or as having CLD (n = 26, abnormal chest X-ray, supplemental O2 requirement +/- ventilator). Urinary LTE4 levels were significantly elevated in CLD compared with the control group (288 +/- 92 versus 35 +/- 10 pg/mg creatinine, mean +/- SE, p < 0.05). Ventilator-dependent CLD patients, who required dexamethasone and had demonstrated uLTE4 levels above the normal range, needed significantly higher peak inspiratory pressures (20 +/- 1 cm H2O versus 15 +/- 1 cm H2O) than similar patients with uLTE4 in the normal range, and the former group had a significant reduction in uLTE4 in the first 5 d of dexamethasone therapy (626 +/- 198 to 451 +/- 176 pg/mg Cr) as ventilatory support was reduced. We conclude that peptidoleukotriene production is activated in patients with CLD (and no other detectable organ dysfunction) to pathophysiologic levels described in adults with acute asthma. Prospective studies focused on infants dependent on high levels of ventilatory support may provide insights into the role of leukotriene synthesis inhibitors or receptor antagonists in the treatment of CLD. PMID- 7881681 TI - Chest physical therapy management of patients with cystic fibrosis. A meta analysis. AB - The purpose of this overview is to quantitatively assess the conflicting body of literature concerning the efficacy of physical therapy modalities for clearing bronchial secretions in the treatment of patients with cystic fibrosis (CF). The modalities examined included positive expiratory pressure (PEP) mask, forced expiratory technique (FET), exercise (EX), autogenic drainage (AD), and standard physical therapy (STD), consisting of postural drainage, percussion, and vibration. Computerized searches of the MEDLINE and Cumulative Index for Nursing and Allied Health databases were performed for the years from 1966 to 1993. The authors of relevant papers were contacted for unpublished information. Studies were considered relevant if they met the following criteria: randomized trials in patients with a definite diagnosis of CF; an intervention of any combination of PEP, FET, STD, AD, or EX; and an outcome of FEV1, sputum weight, or sputum clearance. A review of 456 citations yielded 65 potentially relevant trials and 8 review articles; of these, 35 met the inclusion criteria and were incorporated into the overview. These studies evaluated different combinations of physical therapy modalities; therefore, we performed seven separate meta-analyses comparing the independent techniques using the pooled effect size technique. Standard physical therapy resulted in a significantly greater sputum expectoration than no treatment (effect size of 0.61 SD units, p < 0.0001). The combination of standard therapy with EX with associated with a statistically significant increase in FEV1 over STD alone (effect size of 0.48 SD units, p = 0.04). No other differences between physical therapy modalities were found. PMID- 7881682 TI - Reduced transplant lung volumes after single lung transplantation for chronic obstructive pulmonary disease. AB - Single lung transplantation is now an extremely successful option for the treatment of end-stage chronic obstructive pulmonary disease (COPD). This procedure involves placing a normal sized lung in a hyperinflated hemithorax. Preliminary observations of these patients suggest that the transplanted lung volume is smaller than expected and often the native (COPD) lung increases in volume. The purpose of this investigation was to quantify the volume contributions of the transplant and native lung to the total lung capacity. In seven patients who underwent single lung transplant for end-stage COPD the transplant and native lung volumes were measured by computer-analyzed planimetry immediately after transplant and the following 6 mo post-transplant. The transplant lung volume was smaller than predicted immediately after transplant at only 33 +/- 5% (mean +/- SD) of predicted TLC. This did not change significantly over the next 6 mo. Native lung volume increased following transplant to 74 +/- 19% predicted TLC at 1 mo and 80 +/- 16% at 6 mo. Five of the seven patients subsequently underwent measurement of pleural pressures at TLC. The mean static pleural pressure at TLC was low at -16 +/- 5.1 cm H2O. In summary, following single lung transplantation for COPD the transplanted lung is significantly restricted. We conclude that the likely mechanism of this restriction is due to low transpulmonary pressure generation. PMID- 7881683 TI - SP-A deficiency in primate model of bronchopulmonary dysplasia with infection. In situ mRNA and immunostains. AB - The surfactant protein secretory cells in airway and alveolar epithelium were studied in premature baboons with bronchopulmonary dysplasia and superimposed infection. PRN animals were delivered by hysterotomy at 140 d gestational age and ventilated on clinically appropriate oxygen for a 16-d experimental period. To assess 0 time and sacrifice time gestational parameters, 140 and 156 d were studied. BPD animals were delivered at 140 d and ventilated with positive pressure ventilation and an FIO2 of 1.0 for 11 d followed by 5 d of oxygen sufficient to maintain PAO2 at 40 to 50 mm Hg. BPD-infected animals were comparably ventilated and treated like the BPD group except that 10(8) E. coli organisms were endotracheally instilled on Day 11. In situ hybridization studies for mRNA expression of SP-A, SP-B, and SP-C revealed that an SP-A mRNA deficiency, present at 140 d, persisted in the BPD and BPD-infected groups, whereas SP-A mRNA was abundant in PRN and 156 d gestation control groups. SP-B and SP-C mRNA expression in the two hyperoxically injured groups was particularly extensive in cells around peribronchiolar and perivasicular sites. Immunostaining with SP-A, SP-B, and SP-C antibodies showed variable staining patterns. The study clearly demonstrates that a deficiency of SP-A mRNA expression persists in chronic lung injury and that variable protein staining patterns are manifested depending upon the underlying pathology. PMID- 7881684 TI - Tuberculosis as a primary cause of respiratory failure requiring mechanical ventilation. AB - Tuberculosis as a primary cause of respiratory failure requiring mechanical ventilation (TBMV) is an uncommon occurrence. Over a 10 yr period in the province of Manitoba, Canada (population 1,091,942 in 1991), 13 patients with TBMV were identified. Non-drug-resistant M. tuberculosis was isolated from each case. The patients fell into two categories: miliary or disseminated tuberculosis (n = 7) and tuberculous pneumonia (n = 6); eight developed ARDS (adult respiratory distress syndrome) and another two probable ARDS. The hospital mortality for TBMV was compared with that for mechanically ventilated nontuberculous pneumonia and ARDS patients. Hospital mortality for patients with TBMV (69%, nine of 13) was significantly worse than hospital mortality for patients with nontuberculous pneumonia requiring mechanical ventilation (36%, 34 of 94; p < 0.025) and similar to the hospital mortality for patients with ARDS of any cause (56%, 15 of 27; p > 0.10). APACHE II scores for all groups of patients were similar. Compared with patients with tuberculous pneumonia, patients with miliary or disseminated tuberculosis were significantly more likely to develop TBMV (18.9 versus 0.8%, p < 0.0001). Despite the availability of effective antituberculous drugs, TBMV is often associated with ARDS and carries a similarly high mortality rate. Among patients with pulmonary tuberculosis, those with miliary or disseminated disease are especially prone to develop TBMV. PMID- 7881685 TI - Toxocara-induced eosinophilic inflammation. Airway function and effect of anti-IL 5. AB - The immunoinflammatory response to parasitic nematode infections and allergic diseases have some similarities, the most profound being the increases in eosinophils and serum total IgE concentration. Whether parasitic infections stimulate or inhibit allergic asthma is a matter of debate. We investigated the effect of Toxocara canis (T. canis) infection on airway function in BALB/c mice at various days post-infection. Within 24 h after infection, the trachea responded hyperreactive to carbachol stimulation. Eosinophils, and to a lesser degree lymphocytes, infiltrated the airways causing interstitial and alveolar inflammation (7 d post-infection). Concurrently with cell infiltration, the trachea became hyporesponsive to carbachol whereas the pulmonary resistance was increased and the dynamic compliance decreased. The hyporeactive response could be simulated in vitro by incubating normal tracheae with eosinophil-enriched bronchoalveolar lavage cells obtained from infected mice. The response depended on the number of cells added to the medium, a lower number causing a hyper- and a higher number a hyporeactive response. Anti-interleukin-5 (anti-IL-5) producing hybridoma cells given simultaneously with T. canis infection inhibited eosinophil infiltration in the airways but not that of lymphocytes. Anti-IL-5 treatment prevented tracheal hyporeactivity but not perivascular and peribronchial edema, increased pulmonary resistance, or decreased dynamic compliance. Treatment with isotype control antibody did not affect eosinophil number nor the observed changes in airway functions. It was concluded that T. canis-induced airway inflammation coincided with increased pulmonary resistance, decreased dynamic compliance, and perivascular/peribronchial edema. These phenomena were independent on the presence of eosinophils, whereas tracheal hyporeactivity was clearly associated with airway eosinophilia. PMID- 7881686 TI - Lower airways inflammation during rhinovirus colds in normal and in asthmatic subjects. AB - Human rhinoviruses (HRV) cause the majority of common colds and are etiologically linked with changes in lower airways physiology and asthma exacerbations. We hypothesized that changes in bronchial mucosal inflammatory cell populations may be responsible for HRV-induced changes in airway reactivity. We examined bronchial mucosal biopsies during experimental infections with HRV serotype 16 and measured changes in histamine reactivity. Seventeen adult volunteers (six atopic asthmatics) had baseline measurements of histamine reactivity and fiberoptic bronchoscopic biopsies, followed 2 wk later by viral inoculation. Further bronchial biopsies were taken on Day 4 of the infection and 6 to 10 wk later. Mast cells, eosinophils, lymphocytes, and neutrophils were quantified by immunohistochemical techniques. Infection was documented by viral culture, seroconversion, and symptoms. An increase in histamine responsiveness during the cold (p = 0.048) was accompanied by increases in submucosal lymphocytes (p = 0.050). There was a subsequent decrease in submucosal and epithelial lymphocytes in convalescence (p = 0.028; p = 0.030). There was an increase in epithelial eosinophils with the cold (p = 0.042), and in asthmatics this appeared to persist into convalescence. A peripheral blood lymphopenia correlated with increased responsiveness (r = 0.062, p = 0.014). Rhinoviral colds are associated with a bronchial mucosal lymphocytic and eosinophilic infiltrate that may be related to changes in airway responsiveness and asthma exacerbations. PMID- 7881687 TI - Latex gloves with a lower protein content reduce bronchial reactions in subjects with occupational asthma caused by latex. AB - Latex gloves have been documented as causing rhinitis and asthma. Using inhalation challenges, we evaluated the bronchial response to hypoallergenic gloves in eight health care workers with latex-induced asthma. The subjects were exposed to the powdered latex gloves causing asthma at work and various brands of gloves with a lower protein content, either low-powdered, nonpowdered, or powdered. Exposure to hypoallergenic gloves resulted in the absence (in six subjects) or a significant reduction (in two subjects) of bronchial response. The effects of repeated exposure to hypoallergenic gloves was assessed in two subjects who did not demonstrate changes in peak expiratory flow rates and nonspecific bronchial responsiveness to histamine. This study on a limited number of patients suggests that the use of hypoallergenic gloves could be an effective means of reducing the risk of asthmatic reactions in health care workers with latex-induced asthma when complete avoidance cannot be achieved. The long-term effect of exposure as well as the widespread use of hypoallergenic gloves warrant further investigation on larger cohorts of subjects. PMID- 7881688 TI - Epithelial modulation of leukotriene-C4-induced human tracheal smooth muscle contraction. AB - We investigated the role of epithelium in smooth muscle contraction induced by leukotriene C4 (LTC4) in isolated human trachea. The contractile response to LTC4 was potentiated by a gamma-glutamyl transpeptidase (gamma-GTP) inhibitor L-serine borate and by removal of the epithelium. Both L-serine borate (4.5 x 10(-2) M) and removal of the epithelium shifted the concentration-response curves to LTC4 to lower concentrations by 1.2 and 1.0 log units, respectively. Incubation of cultured human tracheal epithelial cells with either LTC4 or LTD4 resulted in the formation of LTD4 or LTE4. The isolated epithelial cells and cultured epithelial cells contained gamma-GTP activity. Histochemical study indicated that gamma-GTP like activity was present in the epithelial, submucosal, and smooth muscle layers. These findings suggest that the epithelium modulates the contractile response to LTC4 in human trachea by LT-degrading enzymes. PMID- 7881689 TI - Recurrence of diffuse panbronchiolitis after lung transplantation. AB - Diffuse panbronchiolitis (DBP) is characterized by chronic inflammation of the upper and lower respiratory tract. DPB has been found almost exclusively in oriental populations. We describe the occurrence of a case of DPB in an African American patient who underwent bilateral sequential lung transplantation. Ten weeks after transplantation, DPB recurred in the lung allograft, with rapid and significant deterioration in graft function. Allograft function improved within a few weeks after beginning treatment with erythromycin. This early recurrence is suggestive of a systemic etiology of DPB. Although recurrence of other systemic diseases has been reported after lung transplantation, no previous patients have been reported with early functional deterioration based solely on disease recurrence. PMID- 7881690 TI - Clinical, echocardiographic, and hemodynamic evidence of cardiac tamponade caused by large pleural effusions. AB - Large pleural effusions are typically associated with dyspnea and potential respiratory compromise. Experimental evidence suggests that with large effusions, increased intrapleural pressure may be transmitted to the pericardial space, resulting in impaired cardiac filling and reduced stroke volume. We report two cases in which large pleural collections were complicated by hypotension. The effusions were due to an infected right hepatic hydrothorax (Case 1) and a left malignant effusion (Case 2). Echocardiography demonstrated right and left ventricular diastolic collapse, respectively, confirming a diagnosis of cardiac tamponade. Large volume thoracentesis resulted in immediate hemodynamic improvement as demonstrated by a reduction in right ventricular and atrial pressures (Case 1) and echocardiographic resolution of left ventricular diastolic collapse (Case 2). These cases establish that large pleural effusions can cause hemodynamically significant cardiac tamponade. In addition, they illustrate how the demonstration of cardiac compressive physiology can significantly alter the therapeutic approach to large pleural effusions. PMID- 7881691 TI - Interstitial lung disease: a diagnostic approach. Are CT scan and lung biopsy indicated in every patient? PMID- 7881692 TI - Approaches to the treatment of pulmonary fibrosis. AB - There was a general consensus at the workshop that pulmonary fibrosis is a highly lethal lung disorder and that current therapies for this disease have little effect on the natural history of the disease. There was also broad consensus that much has been learned about the pathogenesis of this disease in recent years and this information can be used to direct new therapies for this disease. As a complement to the findings from studies on pulmonary fibrosis itself, there has also been significant development of new therapies for other disorders that might be useful in treating patients with pulmonary fibrosis. The following is a list of some of the issues and recommendations that were generated from this workshop. PMID- 7881693 TI - Pulmonary function abnormalities in thalassemia major. PMID- 7881694 TI - Evaluation of peak expiratory flow variability in an adolescent population sample. PMID- 7881695 TI - Outcome of the treatment for sarcoidosis. PMID- 7881696 TI - Early bactericidal activity and sterilizing activity of ciprofloxacin in pulmonary tuberculosis. PMID- 7881697 TI - Nontuberculous mycobacteria: an underappreciated cause of geriatric lung disease. PMID- 7881698 TI - Aerosolized dornase alfa (rhDNase) for therapy of cystic fibrosis. AB - The major causes of morbidity and mortality in cystic fibrosis (CF) are the obstruction and damaged airways that result from the accumulation of viscid and infected secretions. Dornase alfa, also called recombinant human DNase I (rhDNase), cleaves extracellular DNA, which is present in inordinately high concentrations in purulent CF airway secretions. Dornase alfa has been found to increase the pourability and reduce the viscoelasticity of CF sputum in vitro and, in an animal model, to increase its mucociliary transportability. Short-term (10-day) Phase I and II clinical trials showed dornase alfa to be safe and effective in improving pulmonary function in clinically stable CF patients with mild to moderate pulmonary disease (FVC > or = 40% of predicted value). A long term (24-week) Phase IIB clinical trial demonstrated the importance of administering dornase alfa daily to maintain its efficacy. A large-scale, long term, Phase III clinical trial, consisting of a 24-week double-blind period and a 24-week open-label extension, confirmed these findings and further demonstrated that dornase alfa reduces the incidence of respiratory tract infectious exacerbations requiring parenteral antibiotic therapy. Dornase alfa also decreased the rate of hospitalizations, the number of days missed from work or school, and the frequency of CF-related symptoms. Adverse events were limited to upper airway irritation (i.e., voice alteration, laryngitis, pharyngitis), rash, chest pain, and conjunctivitis. These manifestations generally were mild and transient, and they did not limit the use of dornase alfa. A small proportion (2 to 4%) of patients developed serum antibodies to dornase alfa, but no patient developed anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881699 TI - Pharmacokinetic characteristics for extent of absorption and clearance in drug/drug interaction studies. AB - Many aspects of drug/drug interaction studies, including aspects of the design, choice of pharmacokinetic characteristics, and statistical analysis can be adapted from bioequivalence studies [Steinijans et al. 1991]. However, an important difference between drug/drug interaction studies and bioequivalence studies is that two formulations in bioequivalence studies generally do not differ with respect to the clearance of the drug under investigation, but in drug/drug interaction studies an effect of one drug on the clearance of another drug is not only possible, but the likely mechanism of interaction for many classes of drugs. Thus, while in bioequivalence studies two formulations are conventionally compared with respect to the rate and extent of absorption of the drug, in drug/drug interaction studies equivalence has to be shown with respect to not only the rate and extent of absorption, but also, and in particular, with respect to the clearance of the drug. Consequently, in drug/drug interaction studies the area under the curve is not a pure characteristic of the extent of absorption, but a composite characteristic of extent of absorption and clearance. This should be taken into account when interpreting the results of drug/drug interaction studies. Apart from standard characteristics such as Cmax and AUC used in bioequivalence studies, for drug/drug interaction studies we suggest the elimination half-life as a characteristic for the clearance, and the ratio of AUC and the elimination half-life as a characteristic for the extent of absorption of a drug. PMID- 7881700 TI - Pharmacokinetics and safety of intravenous recombinant human superoxide dismutase (NK341) in healthy subjects. AB - Recombinant human superoxide dismutase (rhSOD), NK341, was intravenously administered to healthy male volunteers at doses of 1750-35000 U/kg, and the safety and pharmacokinetic properties were evaluated. There were no abnormal findings attributable to the test drug throughout the study, showing that NK341 was well tolerated in healthy subjects. Tri-exponential elimination of the drug from blood was observed with half-lives of about 20 minutes (alpha phase), 80 minutes (beta phase), and 6 hours (gamma phase). The values of the maximal plasma concentration and the areas under the plasma concentration curves linearly increased with the doses given. On the other hand, the urinary recovery of the drug also increased with the dose, ranging approximately from 3%-45% of the dose. The plasma concentration of the drug measured by an enzyme immunoassay was quite comparable to SOD activity measured by electron spin resonance, suggesting that NK341 was present in blood as the active form of SOD. PMID- 7881701 TI - The effects of theophylline on serum alprazolam levels. AB - Theophylline and benzodiazepines are frequently combined in clinical practice. Because of a number of case reports about antagonism of benzodiazepine-induced sedation by theophylline, we investigated serum alprazolam levels in a convenient sample of pulmonary medicine inpatients receiving theophylline and no theophylline. One mg of alprazolam was given daily for seven days to 6 patients receiving theophylline and 7 patients not receiving theophylline treatment. On days 2 through 7, trough serum alprazolam levels were measured. On day 7, blood samples were collected before (0 hour), and at 3, 6, 9 and 12 hours after alprazolam administration. In patients receiving theophylline, serum trough alprazolam levels were significantly lower during each day of the study. In patients receiving no theophylline, serum alprazolam levels were in the therapeutic range, except for two patients who had high alprazolam levels. In this small study, serum alprazolam levels were found to be consistently below the therapeutic range in patients receiving chronic theophylline treatment. Previously reported antagonism of anxiolytic effects of benzodiazepines by theophylline is probably due to the lower serum benzodiazepine levels in these patients. PMID- 7881703 TI - Absolute bioavailability of a new high dose methylprednisolone tablet formulation. AB - This was a single-blind, single-dose, randomized crossover study to determine the absolute bioavailability of Medrol, a new high dose (100 mg) methylprednisolone tablet product, by comparing it with 100 mg methylprednisolone from an intravenous formulation, Solu-Medrol. Fourteen healthy, non-smoking, Caucasian male volunteers took part. On treatment days volunteers remained recumbent for 4 hours after drug administration, with food and fluid intake standardized over this period. Serial blood samples were drawn over a 14-hour period after drug administration. Plasma methylprednisolone concentrations were determined by high performance liquid chromatography. The geometric means of AUCi.v. and AUCtablet were 4,049 and 3,334 ng.h/ml, respectively. The absolute bioavailability of the tablet product was 82%, which is in agreement with published data for other oral dosage forms of methylprednisolone. Volunteers displayed the expected rise in peripheral blood neutrophil count, but no other clinically relevant changes in hematology or clinical chemistry were observed. No adverse drug reactions were recorded. It is concluded that the tablet product can be used as a substitute for parenteral methylprednisolone in situations requiring high-dose therapy. PMID- 7881702 TI - Thrombin and platelet inhibition with low-dose calcium-heparin in comparison with ASA in patients with peripheral arterial occlusive disease at Leriche-Fontaine IIb class. AB - Sixty patients with a mean age of 64 years (range 57-77 years), 55 males and 5 females, with peripheral arterial occlusive disease (PAOD) at Leriche-Fontaine IIb class were randomly allocated to receive either subcutaneous calcium-heparin (12,500 IU once daily) or oral acetylsalicylic acid (ASA) (300 mg twice daily), each given for 3 months, followed by a 6-month follow-up period during which no treatment was given. The following parameters were evaluated before randomization, after 1 and 3 months of therapy and after 1, 3 and 6 months of follow-up: pain-free walking distance (PWD), maximum walking distance (WDmax), systolic and diastolic blood pressure, posterior tibial arterial pressure and ankle/arm index at rest and after exercise (treadmill), transcutaneous gas analysis at rest (TcPO2). Under both treatments a statistically significant increase (p < 0.01) in PWD/WDmax was observed after 3 months of therapy. Calcium heparin was slightly but significantly more effective than ASA in prolonging WDmax (p < 0.05) after 3 months of therapy. Both treatment groups maintained the clinical improvement after 6 months of follow-up without any difference between each-other. Both treatments resulted in a statistically significant increase in TcPO2 and decrease in plasma fibrinogen but under calcium-heparin treatment these modifications were doubled in comparison with ASA (p < 0.01 and p < 0.05, respectively for TcPO2 and fibrinogen). The sustained effects on these parameters after 6 months of follow-up could suggest a more direct and multifactorial activity of calcium-heparin on microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881704 TI - Crossover comparison of the effects of enalapril and captopril on potassium homeostasis in patients with mild hypertension. AB - The effects of two types of angiotensin converting enzyme (ACE) inhibitors, enalapril (long-acting) and captopril (short-acting), on serum electrolytes and circadian rhythm of urinary electrolyte excretions were compared in relation to aldosterone status in patients with essential hypertension and normal renal function. Enalapril (5 mg once daily) and captopril (12.5 mg t.i.d.) were administered to 11 patients for 1 week each in a crossover fashion. Blood sampling in the early morning and 4-hour split urinary sampling for 24 hours were performed on the last day of control and each treatment periods. Enalapril and captopril significantly reduced blood pressure to similar levels. Enalapril but not captopril significantly inhibited plasma aldosterone concentration and urinary aldosterone excretion. Neither drug apparently altered serum or urinary Na levels. Both drugs significantly decreased urinary K excretion (p < 0.05, control: 44 +/- 4 mEq/day, captopril: 39 +/- 2 mEq/day, enalapril: 39 +/- 2 mEq/day; mean +/- SEM), but did not significantly alter serum K level (control: 4.1 +/- 0.1 mEq/l, captopril 4.2 +/- 0.2 mEq/l, enalapril 4.3 +/- 0.1 mEq/l). The circadian rhythm (acrophase) of urinary K excretion was not affected by either drug, while the amplitude was decreased by both, as assessed by the cosinor method. In summary, although enalapril caused more sustained inhibition of aldosterone secretion compared with captopril, both drugs showed similar effects on the K homeostasis in patients with mild essential hypertension. PMID- 7881705 TI - Effect of bevantolol and propranolol on serum lipids in patients with essential hypertension. AB - In patients with essential hypertension, the beta-blockers bevantolol or propranolol were administered once or twice a day for twelve weeks to evaluate the effects on blood pressure, and lipid metabolism. Both systolic and diastolic blood pressure decreased significantly in response to both bevantolol and propranolol. The pulse-rate also decreased significantly in both groups. Total cholesterol did not change significantly in both groups. Triglycerides increased significantly in the bevantolol group. HDL cholesterol decreased significantly in the propranolol group. The LDL cholesterol/HDL cholesterol ratio increased significantly in the propranolol group, while no significant increase was observed in the bevantolol group. The apolipoprotein B/A ratio was elevated in the propranolol group. No serious side-effects were noted during the study in both groups. These results indicate that bevantolol is an effective antihypertensive drug with fewer unfavorable effects on lipid metabolism than propranolol. PMID- 7881706 TI - Analysis of pharmacokinetic-dynamic interrelations with special reference to applications in cardiovascular clinical pharmacology. AB - The relationship between a (detectable) cardiovascular response and plasma concentrations is affected by 1. the temporal delay of the equilibrium between sampling site and effector site(s), 2. the intrinsic relationship between the primary effect(s) and concentration at the effector site(s) and 3. inter pharmacodynamic processes that link the primary effects to a net response and that might attenuate or amplify the primary effects. Confounding factors (active metabolites, time-variant protein-binding, enantiospecific pharmacological behavior, physiological counter-regulation, etc.) might confuse the issue even more. Models that address kinetic-dynamic interrelations are usually confined to the first two processes listed above and hardly account for the third factor (and often are inadequate if more than one confounding factor is involved). They yield model-driven assimilative solutions that are characterized by a high level of indetermination. The "fit" of the experimental data with an analytical model (in itself usually quite appealing by its mathematical elegance and inductive creativity) should not be mistaken as a "match" between the model and physio pharmacological "reality". In consequence, these models are cognitive constructions that provide important insight in the complexity of these physio pharmacological processes without necessarily solving it. Their actual "proof" and ultimate value thus lies in their practical applicability (i.e. their effective instrumental use) to predict, correct and optimize (pharmacotherapeutic) response. Unfortunately most models have failed to be successfully tested in this regard. PMID- 7881707 TI - Adverse drug reactions resulting in hospital admission. AB - A 14-month (1992/3) prospective study was performed in two departments of the University Hospital Centre (UHC) in Zagreb. The aim of the study was to assess the rate of drug-related hospitalizations, drugs that caused adverse drug reactions (ADRs), and all factors which could have been of importance for their appearance. One hundred and thirty (2.5%) of 5,227 patients were admitted to hospital because of ADRs. The most frequently ADR-related drugs were nonsteroidal anti-inflammatory drugs and analgesics (64.6%). They were followed by cardiovascular agents (20.8%) and antimicrobials (3.8%). Acetylsalicylic acid (aspirin) caused 38.5% of hospital admissions, other nonsteroidal anti inflammatory drugs (NSAIDs) 23.1% and medigoxin 15.4% of hospitalizations. The most frequent ADRs were upper gastro-intestinal tract bleeding (64.6%), cardiac rhythm disturbances (13.9%), blood cell disorders (4.6%) and hypoglycemia (2.3%). Regarding the patients' age, 52.3% of patients was younger and 47.7% older than 65. Sixty-one point five percent of patients was taking more than one drug, older patients (48 patients--77.4%) have been taking a significantly higher number of drugs than the younger (32 patients--47.1%) (p < 0.0001) ones. Drug interactions caused 23.8% of ADRs. Only 11 (8.5%) of patients suspected themselves that the drug might have caused the ADR. Improvement was observed in the majority of patients (65.4%), 25.4% recovered completely, 4 (3.0%) died in the hospital because of ADRs. 3.0% of patients as well died of their underlying diseases, 2.3% were transferred to other departments for their underlying diseases, and one patient left the hospital on his free will. PMID- 7881708 TI - [Bronchiolitis obliterans: difficulties of definition]. PMID- 7881709 TI - [Transtracheal catheter and liquid oxygen: 5 years of experience]. AB - We studied clinical tolerance, complications, change in pulmonary function test results, arterial gasometrics, hemoglobin (Hb), 6 minute stress tests (6 wt) and subjective perception of dyspnea assessed on a visual analog scale (VAS) in a group of 18 patients (17 with obstructive disease and one with restrictive disease). These patients had previously been enrolled in a home oxygen therapy (HOT) program to deliver continuous oxygen therapy through nasal prongs, and had accepted portable oxygen therapy delivered by transtracheal catheter (TTC) from 1988 until 1993. Tolerance was good, there were no lethal complications of TTC, and excellent compliance with the prescribed HOT was achieved. Lung function test results worsened, while Hb and PaO2 improved and significant oxygen savings (50%) were achieved. The 6 wt test results had not worsened at the end of the first year but did so significantly at the end of the third year, in spite of a relative preservation of lung function. Dyspnea assessed on a VAS was not seen to worsen. We conclude that tolerance of the method was good and that no relevant complications occurred. HOT by TTC did not prevent worsening of bronchial obstruction. Oxygenation of patients was better, as shown by the decrease in Hb and the improvement in PaO2 at the end of the first year of monitoring. Changes in 6 wt showed that in order to achieve greater benefit from HOT by TTC, patients should follow a pulmonary rehabilitation program. PMID- 7881710 TI - [Effects of nasal continuous positive airway pressure on lung function in patients with sleep obstructive apnea syndrome]. AB - Sixty-one patients with obstructive sleep apnea syndrome (OSAS), 26 of whom also had chronic obstructive pulmonary disease (COPD), received treatment by nasal continuous positive airways pressure (nCPAP). To evaluate the effects of this device on daytime lung function, we analyzed pulmonary function tests before treatment with nCPAP and after a mean follow-up period of 12 months (range: 2-22 months). In patients with both OSAS and COPD, we observed a significant decrease in PaCO2 (p < 0.007), in airways resistance (p < 0.002) and in residual volume (p < 0.01); for these same patients we recorded increases in forced vital capacity (p < 0.04) and maximum inspiratory pressure (p < 0.02). We saw no change in lung function in patients with OSAS only. PaO2 increased after treatment in the 15 patients who were initially hypoxemic (p < 0.001). We conclude that after treatment with nCPAP, the greatest changes in respiratory function occur in patients with both OSAS and COPD, who also experience slight decrease in body weight. These changes may be explained by a decrease in auto-PEEP and weight loss. PMID- 7881711 TI - [Smoking of school children in rural Castilla-Leon environment. Attitudes of the school population]. AB - Tobacco smoking is the most important health problem among school-age children and educational programs aiming at prevention must be taken up by all members of the school community (parents, teachers and students) as well as by health providers. We designed an anti-smoking campaign lasting three years directed towards sixth, seventh and eight-grade elementary school students and secondary school pupils attending classes in the area of Vitigudino (Salamanca). We report the results of student attitude surveys done at the beginning of the program. Sixty-eight percent of boys and 50.7% of girls have smoked at some time. The average age of first contact with tobacco was 12.1 +/- 2.4 years, with boys starting to smoke at a significantly younger age (p < 0.001) than girls. At present, 13.7% of school children smoke. The main reasons given for starting to smoke were that friends smoked (56.9%) and curiosity (55.4%). Tobacco smoking in the family was mentioned by only 29.5% of the students surveyed. Knowledge of medical problems related to smoking was limited. Intention to smoke upon leaving school was reported by 9%, while 46.7% did not know if they would smoke. The fact that only 44.1% of school children believe they will not smoke upon leaving school highlights the need to provide support information that will help students abstain. Programs aimed at school children have been shown to help reduce tobacco smoking in this population. An adolescent who learns to avoid tobacco is unlikely to be a smoker in adulthood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881712 TI - [Videothoracoscopy in staging of lung cancer]. AB - We present a review of 108 cases of lung cancer in patients who, for a variety of reasons outlined in this report, underwent video assisted thoracoscopy prior to staging. Overall results of the procedure were positive in 94%. We report the usefulness of this tool for identifying adenopathic locations, for effecting biopsies of tumors that could not be typed by other means, for resecting peripheral nodules for screening purposes, and for making etiological diagnoses of accompanying pleural effusions. For diagnostic purposes, this procedure provides a better image than does conventional thoracoscopy, involves the participation of an endoscopy team and even calls for the presence of a pathologist. We consider video assisted thoracoscopy to be a highly effective tool for avoiding so-called pointless thoracotomies and for completing alternative treatments. Its cost effectiveness is indisputable, as are its low rates of morbidity and mortality. PMID- 7881713 TI - [Bronchogenic carcinoma in nonsmokers]. PMID- 7881714 TI - [Coexistence of bronchogenic carcinoma and active pulmonary tuberculosis]. AB - We describe 9 patients with coincident active tuberculosis of the lung and bronchogenic carcinoma who were all diagnosed within a 5-year period. All were men, with a mean age of 55 +/- 10 years. The principal symptom was toxic syndrome lasting 1-3 months and the most common X-ray sign was alveolar consolidation. Analysis of tissue samples revealed squamous carcinoma (4 cases), adenocarcinoma (4 cases, one of which was bronchioloalveolar) and non-small cell carcinoma (1 case). Tumoral stage was often advanced: IV (44%) and III (33%). The tuberculosis bacillus was isolated in sputum (100%) and in bronchial aspirate (50%); no in vitro resistance was observed. Three patients were treated with radical surgery and three with radiotherapy. Average survival was 3 months in this series. PMID- 7881715 TI - [Pancoast's syndrome secondary to non-Hodgkin's lymphoma]. AB - Pancoast's syndrome is usually found coincident with bronchogenic carcinoma. We describe a case of non-Hodgkin's lymphoma presenting with Pancoast's syndrome in a patient with a history of thoracoplasty. PMID- 7881716 TI - [Pulmonary interstitial disease due to hemochromatosis as a presenting sign of disease]. AB - We present a patient with hemochromatosis whose first sign of disease was an accidental finding of interstitial patterns on a chest film and whose transbronchial biopsy showed traces of iron (Fe) in alveolar macrophages and septal matter. We then looked for deposits in other locations, finding Fe ([+]: 6.964 micrograms) in the dry weight of a cylindrical sample of liver tissue. A Medline search on CD-ROM for 1989 through May of 1994 revealed no references to similar cases. PMID- 7881717 TI - [Pleural empyema caused by Corynebacterium sp]. AB - Until recently Corynebacterium sp. had been considered an infrequent cause of infection in humans. In the last few years, however, it has proven its ability to produce severe pulmonary and extrapulmonary infections, generally in immunodeficient hosts. We present a rare case of an immunocompetent man 68 years old who developed community-acquired pneumonia and left pleural empyema, with Corynebacterium sp. isolated in pleural liquid. Response to thoracic drainage and antibiotic therapy (imipenem and clindamycin) was good. PMID- 7881718 TI - [Agreement of various criteria for normal lung volumes]. PMID- 7881719 TI - [Thoracic injuries]. PMID- 7881720 TI - [Multimodal treatment in "clinical" non-small cell N2 bronchogenic carcinoma. What is the question?]. PMID- 7881721 TI - [Chylothorax and liver cirrhosis]. PMID- 7881722 TI - [Giant diverticula of the mid-esophagus appearing as mediastinal masses in thoracic radiography]. PMID- 7881723 TI - [How to improve the impact factor of our journal]. PMID- 7881724 TI - [Current use, methodology and evaluation of nonspecific bronchial provocation tests in our country]. AB - With the aim of determining the current use of non-specific bronchial inhalation challenge (BIC) testing in Spain, 147 questionnaires were sent to hospitals with pneumology departments or units. The questionnaire covered general, technical and methodological aspects of this diagnostic procedure, as well as its assessment and interpretation. Of the 42 informants who returned questionnaires, mainly from large urban hospitals, 34 reported using BIC. The most widespread criterion applied in deciding to use BIC was the presence of atypical asthma symptoms (33/34). The stimulus most often used was methacholine inhalation (33/34). We found that technical preparation of the drug was highly standardized, but that administration and follow-up protocols differed greatly. There was also great variety in the PC20/PD20 value assigned to indicate bronchial hyperresponsiveness. This study contributes to our better understanding of the current use of BIC in Spain and highlights the need to work toward greater standardization for this diagnostic procedure, to enable us to assess and interpret the results more consistently. PMID- 7881725 TI - Prevention by the tachykinin NK2 receptor antagonist, SR 48968, of antigen induced airway hyperresponsiveness in sensitized guinea-pigs. AB - The involvement of tachykinins in antigen-induced airway hyperresponsiveness (AHR) was characterized pharmacologically in guinea-pigs sensitized to ovalbumin with antagonists of tachykinin NK1 and NK2 receptors, namely SR 140333 and SR 48968, respectively. AHR was illustrated by increased sensitivity to bronchoconstriction provoked by aerosolized acetylcholine in anaesthetized, ventilated animals, administrated 48 h after ovalbumin aerosol challenge. SR 48968 (1 mg kg-1, i.p.), when given once 30 min before the antigen challenge, prevented AHR, whereas SR 140333 did not. These findings suggest that the tachykinin NK2 receptor antagonist, SR 48968, may be useful for investigating mechanisms of tachykinins in the development of airway hyperresponsiveness. PMID- 7881726 TI - 5-HT3 receptor antagonism by anpirtoline, a mixed 5-HT1 receptor agonist/5-HT3 receptor antagonist. AB - 1. The aim of this study was to provide evidence that anpirtoline, which is an agonist at 5-HT1B and 5-HT1D receptors and also displays submicromolar affinity for 5-HT1A recognition sites, in addition, acts as an antagonist at 5-HT3 receptors. 2. In radioligand binding studies on rat brain cortical membranes, anpirtoline inhibited specific binding of [3H]-(S)-zacopride to 5-HT3 receptor recognition sites (pKi: 7.53). 3. In N1E-115 neuroblastoma cells in which [14C] guanidinium was used as a tool to measure cation influx through the 5-HT3 receptor channel, the 5-HT-induced influx was concentration-dependently inhibited by anpirtoline. In this respect, anpirtoline mimicked other 5-HT3 receptor antagonists; the rank order of potency was ondansetron > anpirtoline > metoclopramide. 4. The concentration-response curve for 5-HT as a stimulator of [14C]-guanidinium influx was shifted to the right by anpirtoline (apparent pA2: 7.78). 5. In urethane-anaesthetized rats, anpirtoline inhibited (at lower potency than zacopride and tropisetron) the 5-HT- or phenylbiguanide-induced bradycardia (Bezold-Jarisch reflex), but did not induce this reflex by itself. 6. Intravenous infusion of cisplatin in the domestic pig caused a consistent emetic response which was antagonized by anpirtoline. 7. It is concluded that anpirtoline, which was previously characterized as a 5-HT1 receptor agonist also proved to be a 5 HT3 receptor antagonist in several experimental models and, hence, exhibits a unique pattern of properties at different 5-HT receptors. PMID- 7881727 TI - Characterization of beta 1- and beta 3-adrenoceptors in intact brown adipocytes of the rat. AB - 1. The binding properties of beta 1-, beta 2- and beta 3-adrenoceptors were determined in isolated brown adipocytes of the rat rather than in membrane preparations from tissue homogenates, because typical brown adipocytes represent only about 40% of the various cells present in brown adipose tissue. Binding characteristics were assessed with the hydrophilic beta-adrenoceptor radioligand, (-)-[3H]-CGP 12177. The potent beta-antagonist, bupranolol (100 microM) was used to determine nonspecific binding. Characterization was essentially performed by saturation and competition studies. 2. The saturation curve of (-)-[3H]-CGP 12177 was clearly biphasic (Hill coefficient, nH = 0.57 +/- 0.11, P < 0.01) indicating the presence of two different beta-adrenoceptor populations of high (KD = 0.24 +/ 0.04 nM) and low (KD = 80 +/- 7 nM) affinity. The low affinity sites were more numerous (Bmax = 121,000 +/- 30,000 sites/cell) than the high affinity sites (Bmax = 12,000 +/- 1,000 sites/cell). 3. (-)-[3H]-CGP 12177 (25 nM) was displaced by adrenaline (Ad), noradrenaline (NA), isoprenaline (Iso), phenylephrine (Phe) and by the new beta 3 agonist, CL 316,243 (CL) in a biphasic pattern. The order of potency for (-)-[3H]-CGP 12177 displacement from the small population of high affinity sites (Iso >> NA > Ad >> CL >> Phe was in agreement with a beta 1/beta 2 classification. In contrast, the potencies of the same agonists for displacing the radioligand from the low affinity binding sites (CL >> Iso > NA > Ad >> Phe) revealed the presence of a distinct population of adrenoceptors obeying a beta 3 classification. 5-HT did not displace (-)-[3H]-CGP 12177 (25 nM) when used at concentrations as high as 0.1 mM.4. The beta-adrenoceptor antagonist, (-) bupranolol, was more effective than (-)-propranolol for displacing(- )-[3H]-CGP 12177 (25 nM) from the high (Ki= 0.029 =/- 0.011 and 0.19 +/- 0.07 nM, respectively and low (Ki= 0.27 +/- 0.04 microM and 1.6 +/- 0.2 lM, respectively) affinity binding sites. The selective beta 1 antagonist CGP 20712A efficiently displaced the radioligand from a small population (Ki = 65 +/- 19 pM)of binding sites, confirming the presence of beta 1-adrenoceptors.5. To evaluate whether beta 2-adrenoceptors could be identified in the population of high affinity binding sites, displacement studies were performed at a low concentration of (- ) [3H]-CGP 12177 (4 nM) that mainly labelled beta 1/beta 2-adrenoceptors. ICI 118 551 ( a selective beta 2-antagonist) and procaterol (a selective beta 2-agonist) displaced (- )-[3H]-CGP 12177 from its binding sites with very low affinity (Ki = 0.17 +/- 0.02 micro M and Ki = 11 +/- 2 micro M respectively).6. From these observations, we conclude that: (1) two kinds of binding sites with low and high affinities for (-)-[H]-CGP 12177 can be detected in intact brown adipocytes, (2) there are 10 times more low than high affinity beta-adrenoceptors, as determined by saturation or competition curve analysis, (3) the high affinity binding sites mainly correspond to beta1-adrenoceptors, whereas the low affinity sites represent beta 3-adrenoceptors, and (4) beta 2-adrenoceptors are undetectable.7. It is suggested that the low affinity beta 3-adrenoceptors represent the physiological receptors for noradrenaline secreted from sympathetic nerve endings when the concentration of the neurohormone in the synaptic cleft is very high and/or when the high affinity beta 1-adrenoceptors are desensitized by prolonged sympathetic stimulation such as chronic cold exposure. PMID- 7881728 TI - Selectivity of [125I]-PD151242 for human, rat and porcine endothelin ETA receptors in the heart. AB - 1. Endothelin-1 binds with high affinity to heart where it acts as a potent positive inotropic agent. Our aim was to characterize the labelled and unlabelled ETA-selective antagonist PD151242 in heart tissues derived from man, rat and pigs by use of radioligand binding techniques. 2. Binding of [125I]-PD151242 to sections of human left ventricle was time-dependent and reached equilibrium after 120 min at 23 degrees C with an association rate constant of 0.0235 min-1 nM-1. The binding was reversible at 23 degrees C with a dissociation rate constant of 0.00144 min-1. 3. Saturation binding assays with [125I]-PD151242 revealed a single population of high affinity ET receptors in human left ventricle (KD = 1.07 +/- 0.08 nM; Bmax = 29.8 +/- 4.2 fmol mg-1 protein), porcine left ventricle (KD = 1.92 +/- 0.27 nM; Bmax = 493 +/- 248 fmol mg-1 protein), and rat heart (KD = 0.64 +/- 0.08 nM; Bmax = 82.34.7 fmol mg-1 protein). 4. Unlabelled PD151242 competed with specific [125I]-ET-1 binding to human left ventricle tissue in a biphasic manner with high affinity binding to the ETA-site (KD = 7.21 +/- 2.83 nM) and lower affinity for the ETB-subtype (KD = 104 +/- 23 microM), indicating a greater than 10000 fold selectivity to the high affinity site. 5. The ETA selective ligand FR139317 competed for [125I]-PD151242 binding in human left ventricle with nanomolar affinity (KD = 0.37 +/- 0.10 nM), whereas the ETB selective compound, BQ3020, competed with only micromolar affinity (KD = 1.5 +/- 0.26 microM). 6. The novel ETA-selective radioligand [125I]-PD151242 binds with high affinity to human, rat and porcine heart. In human tissue, binding was shown to be reversible and highly selective for the ETA-subtype making [1251]-PD151242 a useful selective radioligand for further characterization of the ETA-receptor in human tissue. PMID- 7881729 TI - S14080, a peripheral analgesic acting by release of an endogenous circulating opioid-like substance. AB - 1. The oral administration of a benzothiazolinone derivative (benzoyl-6 dihydro 2,3 benzothiazole), S14080, caused dose-dependent antinociception in the rat paw pressure test, which represents a model of mechanical hyperalgesia. S14080 had no significant effect on the inflammatory oedema induced by carrageenin or on the tail flick test, nor did it possess a notable antipyretic effect. 2. Post treatment with S14080 dose-dependently antagonized the hyperalgesia induced by prostaglandin E2, bradykinin, dopamine and by the hyperalgesic cytokines reported to be released by carrageenin (tumour necrosis factor alpha, interleukin-1 and interleukin-8). 3. The blockade of prostaglandin E2-induced paw hyperalgesia by oral pretreatment of the rats with S14080 was abolished by prior intraplantar administration of either naloxone or NorBNI which are non-specific and specific kappa opioid antagonists, respectively. 4. Adrenalectomy abolished the oral antinociceptive effect of S14080. 5. Five consecutive daily injections of S14080 did not produce tolerance such as that seen with the central antinociceptive action of morphine. 6. As with peripherally acting opiates, the antinociceptive activity of S14080 was abolished by the intraplantar injection of agents which inhibit either arginine synthetase (NG-monomethyl-L-arginine) or the activation of guanylate cyclase (methylene blue). 7. We conclude that S14080 is a new type of peripheral antinociceptive which, in rats, acts mainly by releasing an endogenous, opioid-like substance from the adrenal glands. PMID- 7881730 TI - Presence of vasoconstrictor 5HT1-like receptors revealed by precontraction of rabbit isolated mesenteric artery. AB - 1. A series of 5-hydroxytryptamine (5-HT) receptor agonists including 5-HT, 5 carboxamidotryptamine (5-CT) and sumatriptan produced little or no contraction of rabbit isolated mesenteric arteries under resting tone conditions, even at concentrations up to 10(-4) M. 2. When the same agonists were retested in mesenteric artery preparations pre-contracted with the thromboxane-mimetic, U46619, each demonstrated concentration-related vasoconstrictor activity. 5-CT and 5-HT were especially potent and effective in this model giving EC50 values of 4.3 x 10(-9) M and 1.6 x 10(-8) M respectively and maximum effects equivalent to those of KCl 80 mM. In preparations precontracted by U46619 (conditions retained throughout the rest of the study) the order of agonist potency was 5-CT > 5-HT > RU 24969 = sumatriptan > 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) > cisapride. 3. The vasoconstrictor effects of 5-CT were competitively antagonized by methiothepin (pA2 8.20) but resistant to antagonism by a range of other 5-HT receptor antagonists, i.e. pindolol (5-HT1A/5-HT1B), propranolol (5-HT1B), spiperone (5-HT2A), ondansetron (5-HT3), ICS 205930 (5-HT3/5-HT4) and SDZ 205557 (5-HT4). 5-CT responses were slightly antagonized by a high concentration of ritanserin (5-HT2A/5-HT2C). Responses to 5-HT and sumatriptan were also antagonized by methiothepin with similar affinity (pA2/pKB values congruent to 8.0). 4. Metergoline and rauwolscine (10(-7)-10(-6) M) antagonized the effects of 5-CT in a non-competitive fashion giving pKBapp values of 7.13 (metergoline) and 6.86 (rauwolscine). 5. Vasoconstrictor responses to 5-HT were not modified in the presence of ritanserin (3 x 10-7 M) orspiperone (3 x 10-7 M) and only modestly antagonized by ketanserin (10-6 M) suggesting that 5-HT2Areceptors do not make a significant contribution in this model.6. Hence, precontraction of rabbit mesenteric arteries reveals potent vasoconstrictor effects of 5-HT and related agonists. Based on the agonist potency order and the antagonist studies performed, the receptor subtype responsible has the characteristics of a 5-HT1 like (probably 5-HTlD) receptor. This study therefore demonstrates a particularly striking example of vasoconstrictor synergy involving 5-HT1-like receptors. PMID- 7881731 TI - Inhibition by dizocilpine (MK-801) of striatal dopamine release induced by MPTP and MPP+: possible action at the dopamine transporter. AB - 1. The NMDA-type glutamate receptor antagonist, dizocilpine (MK-801) can protect against neurotoxicity associated with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) and its principal metabolite, the 1-methyl-4 phenylpyridinium ion (MPP+). It has been suggested that these neurotoxic effects may be mediated by release of excitatory amino acids, but possible alternative mechanisms have been little investigated. 2. MPTP and MPP+ (0.1-1000 microM) were tested in superfused rat striatal synaptosomes preloaded with [3H]-dopamine. Both MPTP (10 microM and higher) and MPP+ (1 microM and higher) evoked an immediate and concentration-dependent release of [3H]-dopamine. The maximal effect exceeded that achievable with nicotine. For subsequent experiments, submaximal concentrations of MPTP (50 microM) and MPP+ (10 microM) were tested. 3. MK-801 (0.1-100 microM) inhibited responses to MPTP (50 microM) and MPP+ (10 microM) in a concentration-dependent manner. However, further tests of NMDA-type glutamate receptor involvement proved negative. Responses to MPTP or MPP+ were unaffected by the omission of Mg2+ or Ca2+ and were not reduced by the NMDA receptor antagonists, AP-7 (200 microM) and kynurenic acid (300 microM). In this assay, N methyl-D-aspartate (even in the absence of Mg2+ and with added glycine and strychnine) did not evoked [3H]-dopamine release. 4. In crude membrane preparations of rat cerebral cortex, MPTP and MPP+ inhibited high-affinity [3H] nicotine binding to nicotinic cholinoceptors (IC50 1.8 microM and 26 microM, respectively). 5. [3H]-dopamine release evoked by nicotine (1 microM) was blocked by the nicotinic antagonists,mecamylamine and chlorisondamine, and by MK-801 (all at 100 micro M); K+-evoked release was not affected. Release evoked by MPTP and MPP+ was significantly attenuated by MK-801 but not by mecamylamine or chlorisondamine.6. At a high concentration (1O I1M), the selective dopamine uptake inhibitor, nomifensine, completely blocked [3HJ-dopamine release evoked by amphetamine 0.3 microM and MPP+ 10 flM, attenuated responses to MPTP 50 AM and did not affect responses to 12 mM K+. MK-801 100 microM evinced a similar profile but was less effective.7. MK-801 inhibited [3H]-dopamine uptake in striatal synaptosomes with an IC5o of 115 M.8. It is concluded that high concentrations of MK-801 inhibit the acute dopamine release evoked by MPTP and MPP+ in synaptosomes. This antagonism may occur, at least in part, through inhibition of the cell membrane dopamine transporter. MPTP and MPP+ also appear to interact with brain nicotinic cholinoceptors but the functional consequences of this interaction are not yet clear. PMID- 7881732 TI - Cytosolic calcium concentration-force relation during contractions in the rabbit femoral artery: time-dependency and stimulus specificity. AB - 1. By use of front-surface fluorometry with fura-2-loaded rabbit femoral arterial strips, both the cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored. By utilizing the [Ca2+]i-force curves, we were thus able to examine the temporal changes in the relationships between [Ca2+]i and force ([Ca2+]i-force relationship) during contractions induced by a high external K+ solution, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). 2. The 'basic' [Ca2+]i-force relationship of the Ca(2+)-induced contractions was obtained by the cumulative applications of extracellular Ca2+ (0-10 mM) during 118 mM K(+) depolarization (Ca(2+)-contractions). 3. When each vascular strip was exposed to high external K+ (30 mM K(+)-118 mM K+) solutions, the [Ca2+]i abruptly increased until it reached a peak, and then slightly decreased and eventually reached a steady-state level. The force also rapidly rose to reach a maximum plateau level. The changes in [Ca2+]i were more rapid than those in the force. Thus, the [Ca2+]i force curves observed during the contractions induced by high+ (30 mM-118 mM) solutions showed a counter-clockwise rotation, over time. The entire curve shifted to the right, in a concentration-dependent manner, as compared with the line of the 'basic' [Ca2+]i-force relationship of the Ca(2+)-contraction. However, the [Ca2+]i-force relationship of the steady-state of contractions induced by the single dose applications of high K+ (30 mM-118 mM) overlapped with the line of the 'basic' [Ca2+]i-force relationship of Ca(2+)-contractions. 4. As references, the levels of [Ca2+]i and the force at rest (without stimulation) and at the steady-state of the contractions induced by a single dose application of 118 mM K+ solution were designated as 0% and 100%, respectively. When the vascular strips were exposed to NA (10(-5) M) and to 5-HT (10(-4) M), the [Ca2+]i abruptly rose, and reached a peak (107.1 +/- 5.8%) and 101.3 +/- 2.8%, respectively) after 1 min and 2 min, respectively (the [Ca2+]i-rising phase), and thereafter declined with a similar time course (the [Ca2+]i-declining phase) until reaching a low steady level (the steady-state phase). The force induced by 10(-5) M NA and 10(-4) M 5-HT reached a peak at 4 min (129%) and at 2 min (115%), respectively, and thereafter gradually declined. In contrast to the similarity in the [Ca2+]i transient between NA and 5-HT, the force induced by NA declined more slowly and reached higher steady levels than that seen with 5-HT. The level of force 20 min after the application of NA and 5-HT was 112% and 72%, respectively.5. In the entire time course of the 5-HT-induced contraction, i.e., in [Ca2+]i-rising, [Ca2+]i-declining and the steady-state phases, the [Ca2+]i force relation was almost the same as that of the Ca2+-contractions.In the [Ca2+]i-rising phase of NA-induced contraction, the [Ca2+]i-force relation was similar to that of the Ca2+-contractions. However, in the [Ca2+] -declining and the steady-state phases, NA produced a greater force than that expected from a given change in the [Ca2+]i of the Ca2+-contractions, which resulted in a leftward shift of the [Ca2+]i-force relation. The extent of the leftward shift depended on the concentration of NA.6. These results suggest that (1) changes in [Ca2+]i precede changes in the force during the high K+-induced contraction, (2) in the initial [Ca2+]i-rising phase of the contractions induced by NA or by 5-HT, the [Ca2+]i-force relation is similar to that of Ca2+-contractions, and (3) in the subsequent[Ca2+]i-declining and the steady-state phases of the contractions, 5-HT demonstrated little enhancement in force for the given levels of [Ca2+]i, while NA induced a greater force for the given levels of [Ca2+],, in the rabbit femoral artery. Based on the above findings we suggest the presence of a time dependent and stimulus-specific modulation of the Ca2+ sensitivity in the contractile apparatus of arterial smooth muscles. PMID- 7881733 TI - The use of receptor desensitization to analyse CCKA and CCKB/gastrin receptors coupled to contraction in guinea-pig stomach muscle. AB - 1. The results of previous studies have been in conflict with respect to the involvement of specific cholecystokinin (CCKA) and CCKB/gastrin receptors in guinea-pig gastric muscle. Here, in an in vitro, guinea-pig gastric muscle assay, pentagastrin (PG) and tetragastrin (TG) behaved as high potency agonists and produced symmetrical concentration-effect curves. In contrast, cholecystokinin octapeptide (CCK-8), while also behaving as a high potency agonist, produced flat asymmetrical curves. Unlike recent data reported using this tissue (Boyle et al., 1993), the CCKA receptor-selective antagonist, devazepide (3, 10, 30 nM) produced a rightward shift of the upper region of the CCK-8 curve rendering it biphasic. The lower phase was abolished by the CCKB/gastrin receptor-selective antagonist, L-365260 (300 nM) indicating that the contractile effects of CCK-8 in this tissue are mediated by both receptor types. 2. L-365260 produced a concentration dependent, parallel rightward displacement of PG concentration-effect curves. However, a flat Schild plot slope parameter (0.77 +/- 0.06) was obtained. Therefore, an empirical pA2 value of 8.64 +/- 0.21 was estimated from the smallest dose ratio. This value is consistent with published values characteristic of an interaction at CCKB/gastrin receptors. 3. TG (1 microM) was used to densensitize selectively the CCKB/gastrin receptors in the gastric muscle assay and thereby expose a population of receptors capable of responding to subsequent stimulation by CCK-8 but not by PG. The selectivity of TG for CCKB/gastrin- over CCKA receptors was demonstrated by its low efficacy compared to CCK-8 in the guinea-pig gallbladder assay, a tissue shown previously to contain a homogeneous population of CCKA receptors. In TG-desensitized gastric muscle, CCK-8 concentration-effect curves were symmetrical and could be displaced in a simple parallel fashion by devazepide at nanomolar concentrations consistent with an interaction at CCKA receptors (pKB approximately 10). 4. These results indicate that the guinea-pig gastric muscle contains both CCKA- and CCKB/gastrin receptors and the effects of CCK-8 are mediated via both of these receptors. Notwithstanding the complexity of the behaviour of L-365260, it was possible to obtain a reasonable description of the system using a simple 2-receptor model in which the effects of individual receptor activation were assumed to be additive. The absence of a simple competitive interaction of PG with L-365260 may indicate, for example, non-homogeneity of CCKB/gastrin receptors or lack of concentration equilibrium between the bath and the receptor biophase. PMID- 7881734 TI - Failure of nitric oxide donors to alter arrhythmias induced by acute myocardial ischaemia or reperfusion in anaesthetized rats. AB - 1. The aim of the present studies was to examine the effects of nitric oxide donors on arrhythmias induced by coronary artery occlusion and reperfusion, and on cardiac cyclic nucleotides. Experiments were performed in pentobarbitone anaesthetized rats prepared for occlusion of the left coronary artery. 2. Sodium nitroprusside (0.1, 0.3 and 1 microgram kg-1 min-1) had no significant effects on the incidence of ventricular tachycardia, total ventricular fibrillation or the mortality resulting from 25 min of acute myocardial ischaemia when compared with values in controls. In addition, there was no alteration in the number of ventricular premature beats that occurred in survivors. 3. 3 Morpholinosydnonimine-N-ethylcarbamide (SIN-1, 10, 20 and 40 micrograms kg-1 min 1) caused marked hypotension but did not alter the incidence or severity of ischaemia-induced arrhythmias. In rats subject to abrupt reperfusion after 5 min of myocardial ischaemia, lower doses of SIN-1 (1, 3 and 10 micrograms kg-1 min-1) still caused significant reductions in systolic and diastolic blood pressure but were devoid of antiarrhythmic activity. 4. In separate experiments in sham operated rats, sodium nitroprusside (1 microgram kg-1 min-1), isosorbide dinitrate (30 and 60 micrograms kg-1 min-1) and SIN-1 (20 and 40 micrograms kg-1 min-1) had no significant effects on cardiac cyclic GMP content. 5. These results indicate that nitric oxide donors do not alter arrhythmias induced by acute coronary artery occlusion or reperfusion in anaesthetized rats. Although increases in total cardiac cyclic GMP could not be detected, the results suggest that, at least in the rat, cyclic GMP does not influence these arrhythmias. PMID- 7881735 TI - Differential effect of sodium ions and guanine nucleotides on the binding of thioperamide and clobenpropit to histamine H3-receptors in rat cerebral cortical membranes. AB - 1. Conflicting reports in the literature over heterogeneity (West et al., 1990) or homogeneity (Arrange et al., 1990) of histamine H3-receptor binding sites may be attributed to the use of different incubation conditions. In the present study we have investigated the extent to which the binding of H3-receptor ligands to rat cerebral cortical membranes can be modified by both sodium ions and guanine nucleotides. 2. The H3-selective antagonist, thioperamide, discriminated between two specific binding sites for [3H]-N alpha-methylhistamine (IC50 1 = 2.75 +/- 0.87 nM, IC50 2 101.6 +/- 12.0 nM, % site 1 = 24 +/- 2%) in 50 mM Tris HCl buffer, but showed homogeneity of binding in 50 mM Na/K phosphate buffer. 3. Sodium ions markedly altered the binding characteristics of thioperamide (i.e. heterogeneity was lost and IC50 value shifted towards the high affinity site). The competition curves for a second H3-antagonist, clobenpropit and the H3 agonist N alpha-methylhistamine however, were unaltered in the presence of sodium ions. 4. Guanylnucleotides displaced only 60% of specific [3H]-N alpha- methylhistamine binding and modulated thioperamide binding in the same way as sodium ions. 5. These data suggest that the H3-receptor can exist in different conformations for which thioperamide, but not N alpha-methylhistamine and clobenpropit, show differential affinity. 6. The potential nature of these sites, and the implications of this apparent receptor heterogeneity for H3-receptor antagonism by thioperamide, are discussed. PMID- 7881736 TI - Dotarizine versus flunarizine as calcium antagonists in chromaffin cells. AB - 1. Dotarizine is a novel piperazine derivative structurally related to flunarizine that is currently being evaluated in clinical trials for its antimigraine and antivertigo effects. This clinical profile may be related to its Ca2+ antagonist properties. Therefore, the actions of both compounds as calcium antagonists were compared in bovine chromaffin cells. 2. Dotarizine and flunarizine blocked 45Ca2+ uptake into K+ depolarized chromaffin cells (70 mM K+/0.5 mM Ca2+ for 60 s) in a concentration-dependent manner, with IC50s of 4.8 and 6.7 microM, respectively. 3. Dotarizine and flunarizine also inhibited the whole-cell Ca2+ and Ba2+ currents (ICa, IBa) in voltage-clamped chromaffin cells, induced by depolarizing test pulses to 0 mV, during 50 ms, from a holding potential of -80 mV. Blockade exhibited IC50s of 4 microM for dotarizine and 2.2 microM for flunarizine. Dotarizine increased the rate of inactivation of ICa and IBa; inhibition of whole-cell currents was use-dependent. 4. Transient increases of the cytosolic Ca2+ concentration, [Ca2+]i, produced by K+ stimulation (70 mM K+ for 5 s) of single fura-2-loaded chromaffin cells, were also inhibited by dotarizine and flunarizine with IC50s of 1.2 and 0.6 microM, respectively. Upon washout of dotarizine, the [Ca2+]i increases recovered fully after 5-10 min. In contrast, the responses remained largely inhibited 10 min after washing out flunarizine. 5. Catecholamine release induced by K+ stimulation (10-s pulses of 70 mM) was inhibited by dotarizine with an IC50 of 2.6 microM and by flunarizine with an IC50 of 1.2 microM. The blocking effects of both compounds developed slowly, and was fully established after 20-30 min of superfusion. While blockade by dotarizine quickly reversed upon its washout, that of flunarizine lasted even 25 min after washing out.6. Catecholamine release from electroporated chromaffin cells triggered by 10 micro M Ca2+ was not affected by 10 micro M dotarizine or flunarizine.7. Overall, the results suggest that dotarizine behaves as a Ca2+ antagonist in bovine chromaffin cells. It exhibits a potency similar to flunarizine in blocking Ca2+ entry, Ca2+ channels, Cai2+ signals and secretion. The dotarizine effects are readily reversible suggesting that in contrast to flunarizine, it does not accumulate in cells. Dotarizine is devoid of intracellular effects on the secretory machinery. All its blocking effects on Ca2+ entry, [Ca2+]i rise and secretion are probably due to blockade of various Ca2+channel subtypes in chromaffin cells. This blockade is use-dependent and seems to be due to the increase by dotarizine of the rate of Ca2+ channel inactivation. PMID- 7881737 TI - Tonic and use-dependent block of sodium currents in isolated cardiac myocytes by bisaramil. AB - 1. The effects of bisaramil on sodium currents in rat isolated cardiac myocytes were examined by use of tight-seal, whole-cell patch clamp techniques. Bisaramil produced a concentration-dependent, readily reversible reduction in peak transient sodium current. When the sodium current was evoked at 3 s intervals the estimated ED50 for bisaramil was about 11 microM. 2. Bisaramil (16 microM) produced a shift in the inactivation curve to hyperpolarized potentials of about 10 mV, but produced no change in the voltage-dependence of activation. 3. The block of the sodium current by bisaramil showed a profound use-dependence. A concentration of 10 microM produced a considerable block of the current with repeated stimulation. The recovery from block was biphasic, showing fast and slow components which had time constants of about 40 ms and 5 s respectively. 4. Bisaramil produced little tonic block of the sodium current at concentrations of 100 microM; at 300 microM it produced tonic block of around 50%, with extreme use dependence. 5. Bisaramil appeared not to interact primarily with the inactivated form of the channel, since lengthening the depolarizing pulses did not affect the degree of block produced. PMID- 7881738 TI - Regulation of histamine- and UTP-induced increases in Ins(1,4,5)P3, Ins (1,3,4,5)P4 and Ca2+ by cyclic AMP in DDT1 MF-2 cells. AB - 1. Stimulation of P2U-purinoceptors with UTP or histamine H1-receptors with histamine gave rise to the formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) in DDT1 MF 2 smooth muscle cells. 2. Stimulation of P2U-purinoceptors or histamine H1 receptors caused an increase in cytoplasmic Ca2+, consisting of an initial peak, representing the release of Ca2+ from internal stores and a sustained phase representing Ca2+ influx. 3. The P2U-purinoceptor-mediated Ca(2+)-entry mechanism was more sensitive to UTP than Ca(2+)-mobilization (EC50: 3.3 microM +/- 0.4 microM vs 55.1 microM +/- 9.2 microM), in contrast to these processes activated by histamine H1-receptors (EC50: 5.8 microM +/- 0.6 microM vs 3.1 microM +/- 0.5 microM). 4. Pre-stimulation of cells with several adenosine 3':5'-cyclic monophosphate (cyclic AMP) elevating agents, reduced the histamine H1-receptor mediated formation of Ins(1,4,5)P3 and Ins(1,3,4,5)P4. Forskolin completely inhibited Ins(1,4,5)P3 formation (IC50: 158 +/- 24 nM) whereas Ins(1,3,4,5)P4 formation was inhibited by only 45% (IC50: 173 +/- 16 nM). The P2U-purinoceptor mediated production of these inositol phosphates was not affected by cyclic AMP. 5. Forskolin and isoprenaline reduced the histamine-induced increase in cytoplasmic Ca2+, as measured in Ca2+ containing medium and in nominally Ca(2+) free medium but did not change the UTP-induced increase in cytoplasmic Ca2+. 6. These results clearly demonstrate that cyclic AMP differentially regulates components of the histamine induced phospholipase C signal transduction pathway. Furthermore, cyclic AMP does not affect the phospholipase C pathway activated by stimulation of P2U-purinoceptors in DDT1 MF-2 cells. PMID- 7881739 TI - Inhibition of delayed rectifier K(+)-current by levcromakalim in single intestinal smooth muscle cells: effects of cations and dependence on K(+)-flux. AB - 1. Whole-cell voltage-clamp recordings were made from single smooth muscle cells isolated from the longitudinal layer of the guinea-pig small intestine. 2. Levcromakalim ((-)Ckm) inhibited delayed rectifier K-current (IK(DR)) and induced a voltage-independent K-current (IK(-Ckm)). Both effects were inhibited similarly by glibenclamide. In some cells, however, IK(-Ckm) could be induced without any effect on IK(DR). 3. Ba2+ caused a voltage-dependent block of IK(-Ckm). The IC50 was 0.2 mM at -40 mV (6 cells), but at 0 mV 2 mM Ba2+ caused only a 26 +/- 7% inhibition (n = 5). Ba2+ had much less effect on IK(DR), 2 mM Ba2+ having no inhibitory effect on current elicited by depolarization to -30 mV (n = 6) or 0 mV (n = 5). 4. Low concentrations of Zn2+ blocked IK(-Ckm) while having little effect on IK(DR). Zn2+ (40 microM) caused a 77 +/- 1% reduction of IK(-Ckm) at 30 mV (n = 4) but IK(DR) was inhibited by only 10 +/- 3% at the same voltage (n = 4). 5. Inward current amplitudes were compared in 135 mM Rb+ and 135 mM K+ bath solutions. (-)Ckm-activated Rb(+)-current was only 4% of the K(+)-current, whereas delayed rectifier Rb(+)-current was larger than K(+)-current. 6. (-)Ckm did not inhibit IK(DR) if IK(-Ckm) was blocked. In the presence of 2 mM Ba2+ or 135 mM Rb+, (-)Ckm did not induce current nor did it inhibit the delayed rectifier. When [Rb+]o was 25 mM and [K+]J was 130 mM, (-)Ckm elicited outward current and inhibited outward delayed rectifier current (at voltages positive of the reversal potential) but it did not elicit inward current or inhibit inward delayed rectifier current (at voltages negative of the reversal potential).7. These experiments indicate that (-)Ckm-activated K channels are more sensitive to inhibition by Ba2+and Zn2+ and pass inward Rb+ current less well than delayed rectifier K channels. They also suggest that (-)Ckm does not modulate delayed rectifier K channels directly or via an intermediate protein but that the inhibitory effect of (-)Ckm on IK(DR) arises as a consequence of K+-flux through (-)Ckm activated K channels. PMID- 7881740 TI - Mediation by 5-hydroxytryptamine2B receptors of endothelium-dependent relaxation in rat jugular vein. AB - 1. An 'atypical' 5-HT2 receptor which is located on the endothelium of rat jugular vein has been described. In the present study we have further defined the nature of the 5-HT2 receptor subtype present in this preparation. 2. In experiments conducted in the presence of ketanserin to preclude involvement of 5 HT2 receptors, the mixed 5-HT2B/2C antagonist, SB 200646, acted as an antagonist of 5-HT at the endothelial 5-HT receptor (pA2 = 7.2). Yohimbine, which exhibits negligible affinity for rat 5-HT2C receptors but has high 5-HT2B receptor affinity, acted as a potent but non-surmountable antagonist (pA2 > or = 7.3) in rat jugular vein. Neither yohimbine nor SB 200646 affected endothelium-dependent relaxations induced by carbachol. 3. Mianserin also acted as a surmountable antagonist (pA2 = 7.3) and the 5-HT2B agonist, BW 723C86, acted as a potent partial agonist (pEC50 [95% C L], intrinsic activity +/- s.e. mean = 7.9 [7.6 8.3], 0.84 +/- 0.04). Responses to BW 723C86 were antagonized by SB 200646 (0.3 microM) yielding an 'apparent' pA2 [95% CL] of 7.03 [6.76-7.32]. 4. These data are consistent with the presence of 5-HT2B receptors mediating endothelium dependent relaxation of rat jugular vein. PMID- 7881741 TI - In vivo pharmacological characterization of the non-peptide endothelin receptor antagonist SB 209670. AB - 1. The aim of the present study was to assess the ability of SB 209670, a high affinity non-peptide endothelin receptor antagonist (0.4 and 18 nM Kis at human cloned ETA and ETB receptors, respectively), to inhibit the haemodynamic actions of endothelin-1 in vivo. 2. Systemic administration of (+/-)-SB 209670, given either as a bolus i.v. injection or as a continuous i.v. infusion, did not alter basal haemodynamic parameters in the anaesthetized rat. 3. Infusion of (+/-)-SB 209670 (10 micrograms kg-1 min-1) selectively inhibited the depressor and carotid vasodilator response to exogenous endothelin-1: 100 micrograms kg-1 min-1 was required to inhibit significantly the biphasic haemodynamic actions of endothelin 1. The haemodynamic actions of angiotensin II and calcitonin gene-related peptide were unaltered by 100 micrograms kg-1 min-1 (+/-)-SB 209670. 4. Bolus i.v. administration of (+/-)-SB 209670 (1 mg kg-1) selectively inhibited the depressor and carotid vasodilator actions of endothelin-1: 10 mg kg-1 (+/-)-SB 209670 was required to inhibit the secondary vasoconstrictor actions of endothelin-1. 5. (+/ )-SB 209670 (10 mg kg-1) was also effective at antagonizing the pressor actions of endothelin-1 in the conscious rat for up to 3 h after intraduodenal administration thereby demonstrating that the antagonist was bioavailable upon enteric administration. This dose of (+/-)-SB 209670 did not alter basal haemodynamic parameters in the conscious rat. 6. Thus, ( +/- )-SB 209670 is an effective endothelin receptor antagonist in vivo. Using the doses defined in this study, SB 209670 may, therefore, serve as a useful tool for understanding the role of endogenous endothelin-I in the control of cardiovascular function under both physiological and pathophysiological conditions. PMID- 7881742 TI - Contribution of a cholinergic reflex mechanism to allergen-induced bronchial hyperreactivity in permanently instrumented, unrestrained guinea-pigs. AB - 1. In conscious, permanently instrumented, unrestrained, ovalbumin-sensitized guinea-pigs the development of allergen-induced bronchial hyperreactivity to histamine- and methacholine-inhalation was investigated after the early as well as after the late asthmatic response. 2. The allergen-induced increase in bronchial reactivity to histamine was significantly higher than to methacholine. 3. The muscarinic receptor antagonist, ipratropium bromide (1.0 mM, 3 min inhalation), blocked methacholine-induced bronchoconstriction and caused a significant 1.7 fold inhibition of the histamine-induced bronchoconstriction of control animals. 4. A lower dose of ipratropium bromide (0.1 mM, 3 min inhalation) had no significant effect on histamine-induced bronchoconstriction in control animals, but significantly reduced the allergen-induced increase in bronchial reactivity to histamine between the early and late asthmatic response. At 1.0 mM ipratropium bromide, no further reduction was observed. 5. These results clearly indicate that an exaggerated cholinergic reflex mechanism contributes to allergen-induced bronchial hyperreactivity to histamine. PMID- 7881743 TI - Species-related differences in inotropic effects of angiotensin II in mammalian ventricular muscle: receptors, subtypes and phosphoinositide hydrolysis. AB - 1. Experiments were carried out to clarify the mechanisms responsible for variations in the positive inotropic effect (PIE) of angiotensin II (AII) on ventricular muscles from various mammals. We examined the density of AII receptors, the relative proportions of receptor subtypes and the acceleration of the hydrolysis of phosphoinositide that was induced by AII, as well as the PIE of AII in ventricular muscles from the rabbit, dog, rat and ferret. 2. In the rabbit, AII (1 microM) in the presence of bupranolol (0.3 microM) and prazosin (0.1 microM) elicited a concentration-dependent PIE, which was antagonized by a selective AT1 subtype antagonist, losartan, but not by an AT2 antagonist, PD123319. AII did not have any inotropic effects in ventricular muscles from the dog, rat and ferret. 3. Specific high-affinity binding of [125I]-AII, with a similar Kd value in each case (1-2 nM), was observed with membrane fractions derived from ventricular muscle of all four species tested. 4. In the rabbit, losartan and PD123319 each displaced approximately 50% of [125I]-AII specific binding having high affinity for the receptors, and indicating that AT1 and AT2 subtypes were present in equal numbers. In the other species the AT1 subtype of receptors was predominant. 5. In all four species AII caused a concentration dependent acceleration of the hydrolysis of phosphoinositide in ventricular slices that had been prelabelled with myo-[3H]-inositol. 6. The results indicate that the signal-transduction process distal to acceleration of the hydrolysis of phosphoinositide may be responsible for the wide range of species variations in the inotropic action of AII on mammalian ventricular myocardium. PMID- 7881744 TI - Desensitization of the nicotine-induced mesolimbic dopamine responses during constant infusion with nicotine. AB - 1. The effects of constant nicotine infusions (0.25, 1.0 and 4.0 mg kg-1 day-1) on extracellular dopamine levels in the nucleus accumbens (NAc) and on locomotor activity have been compared with the changes evoked by repeated daily injections (0.4 mg kg-1 day-1 for 5 days) of the drug. 2. The extracellular dopamine concentration in the NAc was significantly increased (P < 0.05) following a challenge dose of nicotine (0.4 mg kg-1, s.c.) in animals which had been pretreated with daily injections of the drug. This effect was accompanied by an enhanced locomotor response to nicotine. 3. The stimulant effects of nicotine on mesolimbic dopamine secretion and on locomotor activity were significantly inhibited (P < 0.01) by the prior administration of mecamylamine (2.0 mg kg-1, s.c.) but not by hexamethonium (2.0 mg kg-1, s.c.). 4. The constant infusion of nicotine at a rate of 1 and 4 but not 0.25 mg kg-1 day-1 abolished the sensitized dopamine response in the NAc to an injection of nicotine in animals pretreated with the drug. The locomotor responses to nicotine in the nicotine-pretreated rats were significantly attenuated by the infusion of nicotine at all 3 doses, although the nicotine induced locomotor activity, in the rats infused with 0.25 mg kg-1 day-1 was also significantly (P < 0.05) higher than that observed in the rats treated acutely with nicotine. 5. Significantly (P<0.01) enhanced mesolimbic dopamine responses, to a challenge injection of nicotine(0.4 mg kg-1, s.c.), were observed 2 and 7 days after termination of the infusion of nicotine (4 mg kg-1 day-1 for 14 days); locomotor responses were enhanced (P<0.01) 1, 2 and 7 days after termination of the infusion.6. The results suggest that sensitized mesolimbic dopamine responses to nicotine occur as a result of stimulation of centrally located nicotinic receptors but that these receptors may be desensitized during periods of chronic exposure to nicotine at doses which may be relevant to smoking. PMID- 7881745 TI - Postsynaptic nicotinic receptor desensitized by non-contractile Ca2+ mobilization via protein kinase-C activation at the mouse neuromuscular junction. AB - 1. Non-contractile Ca2+ mobilization (unaccompanied by muscle contraction) was initiated by nerve stimulation in the presence of neostigmine (more than 0.03 microM) at the endplate region of mouse diaphragm muscles. In the process of nicotinic receptor desensitization, the depressant effect of non-contractile Ca2+ on contractile Ca2+ mobilization was investigated by measurement of Ca(2+) aequorin luminescence. 2. When the phrenic nerve was stimulated with paired pulses having intervals of 150, 300, 600, 1000 and 2000 ms, contractile Ca2+ transients were elicited during the generation of non-contractile Ca2+ mobilization. The amplitude of the contractile Ca2+ transients elicited by the second pulse (S2) was depressed at the shorter pulse intervals, but recovered to the initial contractile response (S1) at longer pulse intervals. 3. The extent of depression of S2 was enhanced by increasing the concentration of neostigmine (0.03 to 0.3 microM). When a low concentration (0.05 microM) of pancuronium, a competitive nicotinic antagonist, completely blocked non-contractile Ca2+ mobilization, the depression of S2 was diminished. 4. The depression of S2 was enhanced when the peak amplitude of non-contractile Ca2+ mobilization was raised by increasing the external Ca2+ concentration from 1.3 to 5 mM. 5. Staurosporine (10 nM), a protein kinase-C inhibitor, diminished the depression of S2 despite large amounts of non-contractile Ca2+ mobilization. The diminishing effect of staurosporine was counteracted by TPA (0.1 microM), a protein kinase-C activator. 6. These findings suggest that non-contractile Ca2+ mobilization may enhance the desensitization of the postsynaptic nicotinic receptor via activation of protein kinase-C at the neuromuscular junction. PMID- 7881746 TI - Inhibitory action of SR33557 on L-type calcium current in single ventricular myocytes of rat. AB - 1. The effect of SR33557 on L-type Ca2+ currents in rat ventricular myocytes was investigated by use of the whole-cell patch-clamp technique. 2. SR33557 inhibited Ca2+ current (ICa) in a concentration-dependent manner without change in the current-voltage relationship. 3. The inhibitory effect of SR33557 on ICa was dependent on the holding potential (Vh). The IC50 values were estimated to be 2.2 x 10(-8) M at Vh = -50 mV and 9.0 x 10(-6) M at Vh = -80 mV. SR33557 (10(-7) M) shifted the steady state inactivation curve of ICa toward more negative potentials. Thus, the affinity of the drug for inactivated channels was considerably higher than for resting channels. 4. Blockade of ICa by SR33557 was both tonic and use-dependent. 5. The time constant of onset of block was 36.4 s at -50 mV and 41.9 +/- 11.1 s at -40 mV. 6. The time course of unblock was voltage-dependent. The time constant declined from 400.7 +/- 68.1 is at -50 mV to 5.2 +/- 1.2 s at -80 mV. 7. The rate of block of ICa was related to the number of openings per unit time and to the amount of time spent depolarized. The affinity of drug for open channels was considered to be similar to that for inactivated channels. 8. These results suggest that SR33557 inhibits L-type Ca2+ current through binding to both open and inactivated channels in rat ventricular myocytes. PMID- 7881747 TI - Inhibition by wortmannin of M-current in bullfrog sympathetic neurones. AB - 1. The actions of wortmannin, an inhibitor of myosin light chain kinase (MLCK), on M-type potassium current of dissociated bullfrog sympathetic neurones have been examined. 2. The amplitude of M-current was measured by whole cell recordings from cells pretreated with wortmannin (0.01-10 microM) or the wortmannin vehicle, dimethylsulphoxide (0.0001-0.1 vol%), for 30 min. Internal (recording pipette) solutions having three different pCa values (6, 7 and 8) were used for the measurements. 3. Irrespective of the pCa, M-current was not detectable when the cells were pretreated with 10 microM wortmannin. Wortmannin, 3 microM, produced 85-95% inhibition of the M-current. Pretreatment with 10-30 nM wortmannin was without effect on M-current. 4. The M-current inhibition by wortmannin at concentrations of 0.1-1 microM depended on the pCa of the internal solution. Inhibition occurred only when the calcium-rich (pCa = 6) internal solution was used. 5. Pre-treatment of the cells with wortmannin (10 microM) did not affect rapidly-inactivating A-type or delayed rectifier-type potassium currents not did it alter inwardly rectifying sodium-potassium current (IH). 6. These observations show that M-current inhibition by wortmannin has two pharmacological profiles. One is calcium-dependent and occurs at lower concentrations (0.1-1 microM), and is attributed to inhibition of MLCK by wortmannin. At higher concentrations (3-10 microM), wortmannin has an additional, calcium-independent action, inhibiting the M-current by an unknown mechanism. PMID- 7881748 TI - Comparisons of the effects of nicorandil, pinacidil, nicardipine and nitroglycerin on coronary vessels in the conscious dog: role of the endothelium. AB - 1. The vasodilator properties of nicorandil on large and small coronary arteries were compared to those of nicardipine, pinacidil, nitroglycerin and acetylcholine in six conscious dogs. 2. Intravenous bolus injections of acetylcholine (0.1 micrograms kg-1), nitroglycerin (0.3-3 micrograms kg-1), pinacidil (10-100 micrograms kg-1), nicardipine (3-30 micrograms kg-1) and nicorandil (10-100 micrograms kg-1) dose-dependently increased circumflex coronary artery diameter and decreased coronary vascular resistance, indicating vasodilator effects on both conduit and resistance coronary arteries. 3. Three days after removal of the endothelium of the circumflex coronary artery (balloon angioplasty), pinacidil- and nicardipine-induced dilation of large coronary arteries was greatly reduced (both -76%, P < 0.01) whereas that produced by nitroglycerin and nicorandil was decreased only slightly and to a similar extent for both drugs (-19%, P < 0.01 and -28%, P < 0.05, respectively). 4. Thus in conscious dogs, nicardipine- and pinacidil-induced dilatation of large coronary arteries is endothelium-dependent. In contrast, the vasodilator effects of nitroglycerin and nicorandil on conduit vessels are endothelium-independent. 5. Finally, our results demonstrate that nicorandil dilates the large coronary arteries through its nitrate-like action and that the ATP-potassium channel opening properties of the drug are not involved in this effect in the conscious dog. PMID- 7881749 TI - Electrophysiological effects of SD-3212, a new antiarrhythmic agent with vasodilator action, on guinea-pig ventricular cells. AB - 1. The effects of SD-3212 on transmembrane action potentials were examined in right ventricular papillary muscles and in single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, SD-3212 > or = 3 microM caused a significant decrease in the maximum upstroke velocity (Vmax) of action potential without affecting resting membrane potential. The inhibition of Vmax was enhanced at higher stimulation frequencies. 3. In the presence of SD-3212, trains of stimuli at rates > or = 0.5 Hz led to a use-dependent inhibition of Vmax. The time constant for the recovery of Vmax from the use-dependent block was 1.3 s. 4. Voltage-dependence of Vmax inhibition by SD-3212 was investigated in single myocytes. The curves relating membrane potential and Vmax were shifted by SD-3212 (10 microM) in a hyperpolarizing direction by 6.2 mV. 5. In myocytes treated with SD-3212 (10 microM), the Vmax of test action potentials preceded by conditioning clamp to 0 mV was decreased progressively as the clamp pulse duration was prolonged. Vmax of test action potentials following a long (1 s) 0 mV clamp recovered at a time constant ranging from 1.01 to 1.22 s, being shorter at the more negative potential within a range from -70 to -90 mV. 6. These findings suggest that the primary electrophysiological effect of SD-3212 is a use- and voltage-dependent inhibition of sodium channels. From the onset and offset kinetics of the use-dependent block, SD-3212 is located between fast and intermediate kinetic Class-I drugs. From the state-dependence of sodium channel block, SD-3212 belongs to inactivated channel blockers. PMID- 7881750 TI - A reassessment of the modulatory role of cyclic AMP in catecholamine secretion by chromaffin cells. AB - 1. The role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in the regulation of catecholamine (CA) secretion in chromaffin cells remains equivocal from previous studies. 2. In the present study the effect of this cyclic nucleotide on basal CA secretion, as well as on intracellular calcium and membrane potential has been examined. 3. Forskolin and the permeable cyclic AMP analogue, 8-(4-chlorphenylthio)-adenosine-3'-5' monophosphate cyclic (pClpcAMP), increased basal CA secretion in a dose-dependent manner. The EC50s were 0.43 +/- 0.10 microM for forskolin and 39 +/- 9 microM for pClpcAMP. Other agonists with adenylate cyclase activity such as stimulants of adenosine receptors, beta adrenoceptors, GABAB receptors and intestinal vasoactive peptide (VIP), also increased basal CA secretion in a highly significant manner. However, when they were added together with forskolin, CA secretion was not affected although an additive increase in cyclic AMP levels was produced. 4. Statistical analysis of the correlation between cyclic AMP levels and CA secretion evoked by these cyclic AMP increasing compounds showed that a significant direct correlation between both parameters existed only when low levels of cyclic AMP were produced by secretagogue stimulation. When the increase in intracellular cyclic AMP concentrations exceeded approximately 8 times the basal cyclic AMP levels the correlation was not significant. These results indicate a dual dose-dependent effect of cyclic AMP on basal CA secretion. 5. The stimulatory effect of low cyclic AMP on basal CA secretion was accompanied by an increase in membrane potential and in intracellular calcium concentrations ([Ca2+]j), the latter mainly being due to an increase in intracellular Ca2+ entry through L-type voltage-dependent Ca2" channels.6. The possible mechanisms involved in these cyclic AMP effects are discussed. PMID- 7881751 TI - Different effects of endothelin-3 on the Ca2+ discharge induced by agonists and Ca(2+)-ATPase inhibitors in human platelets. AB - 1. The present study demonstrates that endothelin-3 (ET-3), previously shown to attenuate thrombin-evoked aggregation of human platelets, delayed the dose dependent aggregatory response to thapsigargin (Tg). As this Ca(2+)-ATPase inhibitor induces platelet activation in part through the depletion of internal Ca(2+)-stores, we examined the influence of ET-3 on Ca2+ discharge from internal pools. 2. Cytosolic Ca2+ concentration was evaluated with Fura-2 in the absence of Ca2+ influx. Platelet preincubation for 15 min with 5 x 10(-7) M ET-3 decreased the Ca2+ release evoked by thrombin and U46619, a thromboxane-mimetic. However, ET-3 did not affect Ca2+ movements induced by 1 microM ADP. Addition of Tg (0.5 to 5 microM) to resting platelets induced a cytosolic [Ca2+] rise with concentration-dependent increase of the initial rate and decrease of the time to reach the peak. ET-3 slowed down these dose-dependent effects with a more marked influence on the responses induced by low concentrations of Tg. 3. ET-3 did not modify the Ca2+ response to another Ca(2+)-ATPase inhibitor, 2,5-di-(tert-butyl) 1,4-benzohydroquinone(tBuBHQ). The thromboxane A2 receptor antagonist, SQ 29548, reduced by 53% the calcium signal evoked by 1 microM Tg, which became similar to that induced by 15 microM tBuBHQ. Under these conditions, the ET-3 effects were suppressed. A subsequent addition of thrombin induced a substantial further Ca2+ increase which was again sensitive to ET-3. 4. ET-3 attenuates Ca2+ mobilization from an internal pool dependent on the stimulation of thrombin and thromboxane A2 receptors and insensitive to the direct effect of Ca2+-ATPase inhibitors. The small but significant inhibitory effect of ET-3 leads us to propose that endothelin-3 acts as a modulator of platelet activation. PMID- 7881752 TI - Characterization of alpha 1-adrenoceptors mediating vasoconstriction to noradrenaline and nerve stimulation in the isolated perfused mesentery of rat. AB - 1. The objective of this study was to investigate the alpha 1-adrenoceptor subtype(s) mediating vasoconstrictor responses to perfused and neuronally released noradrenaline (NA) in the isolated perfused mesentery preparation of rat. 2. Isolated mesenteric preparations (with gut attached) from male Sprague Dawley rats (250-300g) were perfused via the superior mesenteric artery with oxygenated Krebs solution at approximately 6 ml min-1. The effects of antagonists on vasoconstrictor responses to either perfused (+/-)-NA or periarterial nerve stimulation (70 V, 2 ms pulse width, 10 s train) were determined. 3. Vasoconstrictor responses to perfused NA were antagonized by prazosin (pA2 = 9.3 +/- 0.1), WB4101 (pA2 = 9.6 +/- 0.1), 5-methyl urapidil (5-MU: pA2 = 9.0 +/- 0.1), (+)-niguldipine (insurmountable) and spiperone (pA2 = 7.7 +/- 0.1). The insurmountable nature of the antagonism by (+)-niguldipine (0.1 nM) was greatly reduced by co-perfusion with prazosin (10 nM). Chloroethylclonidine (CEC: 100 microM for 20 min, followed by 40 min washout) caused an approximate twofold increase in the EC50 for (+/-)-NA and reduced the maximum response by approximately 25%. Pre-treatment of tissues with CEC (100 microM as above) did not significantly alter affinity estimates for prazosin (pA2 = 9.2 +/- 0.1), WB4101 (pA2 = 9.3 +/- 0.1) or 5-MU (pA2 = 8.7 +/- 0.2). Vasoconstrictor responses to periarterial nerve stimulation were antagonized by WB4101 > 5-MU > prazosin >> spiperone. CEC (100 microM as above) reduced nerve-stimulated responses by approximately 50%. 4. The affinity estimates for the various antagonists studied suggest that vasoconstrictor responses to both exogenous and neuronally-released NA are mediated via the same a,-adrenoceptor subtype. The pharmacological profile most resembles the 'classical' alpha l A-adrenoceptor, which, in turn, appears to be a rat homologue of the cloned bovine alpha lc-adrenoceptor. PMID- 7881753 TI - Further characterization of [3H]-CGS 21680 binding sites in the rat striatum and cortex. AB - 1. The putative high affinity binding site for the adenosine A2A receptor agonist 2-p-(2-carboxyethyl)phenethyl-amino-5'-N- ethylcarboxamidoadenosine (CGS 21680) in the rat cerebral cortex was characterized by use of a number of selective A1 and A2 adenosine receptor ligands, and compared to the characteristics of the more abundant striatal A2A receptor. 2. The binding of [3H]-CGS 21680 to cortical membranes was performed at pH 5.5, in order to increase the amount of specific binding. 3. Reduction of the pH from 7.4 to 5.5 increased the apparent affinity of the striatal binding side for both agonists and antagonists. The relative order of potencies of both groups of ligands were the same at both pH values, and were consistent with binding to the A2A receptor. There was no observable change in the Bmax, the values being 415 and 446 fmol mg-1 protein at pH 5.5 and 7.4 respectively. 4. The cortical binding site yielded a Bmax value of 117 fmol mg-1 protein. The relative order of potencies of the adenosine receptor ligands observed at this binding site were not the same as those observed in the striatum, exhibiting a profile with both A1 and A2 characteristics. 5. Further characterization of this cortical binding site in the presence of the A1 selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) revealed a more typical A2A profile. This indicated that under the conditions used there were two components of [3H]-CGS 21680 binding, approximately 20% of the A1 receptor and 80% to the A2A receptor. 6. It is concluded that in the cerebral cortex there is a CGS 21680 binding site showing the characteristic properties of the striatal A2A receptor, and no evidence was obtained for the existence of a novelA2A-like binding site. PMID- 7881754 TI - Modulation of Ca(2+)-dependent currents in metabolically stressed cultured sensory neurones by intracellular photorelease of ATP. AB - 1. The whole cell recording technique was used to study high voltage-activated Ca2+ currents and Ca(2+)-activated Cl- tail currents from cultured neonatal dorsal root ganglion neurones of the rat which were metabolically stressed. The neurones were metabolically stressed with 2-deoxy-D-glucose (5 mM) for 30 min to 3 h. The aim of the project was to examine the actions of intracellular photorelease of ATP on the properties of Ca(2+)-dependent currents and determine if the effects of metabolic stress could be reversed. 2. The mean duration of Ca(2+)-activated Cl- tail currents was significantly increased by metabolic stress and this effect was reversed by intracellular photorelease of approximately 300 microM ATP. Intracellular photolysis of 'caged' photolabile compounds was achieved with a xenon flash lamp. 3. Intracellular photorelease of ATP and adenosine 3':5'-cyclic monophosphate (cyclic AMP) (about 40 microM) also accelerated the inactivation of high voltage-activated Ca2+ currents evoked by 500 ms depolarizing step commands from -90 mV to 0 mV. This effect was prevented by intracellular application of the calcineurin (protein phosphatase-2B) inhibitor cyclosporin A (14 nM) and cyclophilin A (50 nM) either applied together or individually. In contrast the protein phosphatase 1 and 2A inhibitor, calyculin A, increased voltage-activated Ca2+ currents, but failed to prevent enhanced inactivation induced by intracellular photorelease of ATP. Intracellular photorelease of ATP had no effect on Ca2+ currents recorded from control neurones which were not metabolically stressed and supplied with glucose and ATP in the extracellular and patch pipette solutions respectively. 4. In conclusion, intracellular photorelease of ATP increases the decay of Ca2+-activated Cl- tail currents in metabolically stressed neurones suggesting that the efficiency of intracellular Ca2+ buffering was improved. Additionally, an ATP/cyclic AMP dependent component of high voltage-activated Ca2+current inactivation which is mediated by calcineurin is revealed following photolysis of 'caged' ATP or cyclic AMP in metabolically stressed neurones. PMID- 7881755 TI - Secretion of endothelin-1 and endothelin-3 by human cultured vascular smooth muscle cells. AB - 1. It is generally accepted that endothelial cells secrete endothelin (ET) to the underlying media which mediates the contractile effects of ET. However, there is some evidence that animal vascular smooth muscle cells (VSMCs) also secrete ET. We cultured VSMCs from human vessels representative of a number of different vascular beds to determine whether human VSMCs endogenously secrete ET. 2. VSMCs explanted from adult arterial vessels secrete picomolar quantities of immunoreactive mature ET: coronary artery 226.6 +/- 58.8 pM/10(6) cells (n = 7), thoracic aorta 169.5 +/- 105.4 pM/10(6) cells (n = 3), left internal mammary artery 102.4 +/- 23.1 pM/10(6) cells (n = 3) and saphenous vein 69.4 +/- 19.9 pM/10(6) cells (n = 3), as well as from umbilical vein (HUVSMCs) 38.3 +/- 4.3 pM/10(6) cells (n = 3). Secretion of immunoreactive big ET-1 was also detected: coronary artery 249.1 +/- 59.4 pM/10(6) cells (n = 7), thoracic aorta 120.0 +/- 13.4 pM/10(6) cells (n = 3), left internal mammary artery 170.0 +/- 68.2 pM/10(6) cells (n = 3), saphenous vein 105.1 +/- 30.7 pM/10(6) cells (n = 3) and from umbilical vein 146.3 +/- 7.4 pM/10(6) cells (n = 3). Comparable, intracellular levels of immunoreactive big ET-1 and mature ET were also detected in cultured VSMCs. 3. Since enzyme-dispersed VSMCs are thought to be more differentiated and more closely resemble their in vivo counterparts, and these enzyme-dispersed VSMCs from human umbilical vein (HUVSMCs) also secreted the greatest levels of immunoreactive peptides, they were characterized further. Reverse transcription polymerase chain reaction assay demonstrated that HUVSMCs express ET-1 mRNA. High performance liquid chromatography coupled to radioimmunoassay revealed that HUVSMCs secrete ET-1 and ET-3, in addition to big ET-1. However, levels of ET are not altered by 100 AM phosphoramidon,an inhibitor of metalloproteases or by 100 microM pepstatin A, an aspartyl protease inhibitor.4. In concordance, KD and Bmax values for [125I]-ET-l saturation binding are not altered in HUVSMC cultures incubated for 24 h with 100 microM phosphoramidon (431 +/- 218 PM and 31.1 +/- 12.7 fmol mg-1;mean =/- s.e.mean, n = 3) or 100 microM pepstatin A (381 +/- 169PM and 19.9 +/- 7.8 fmol mg-1, n = 3) as compared to controls (355 +/- 99 pM and 33.3 +/- 9.3 fmol mg-1; n = 3). This observation indicates the absence of an autocrine 'unmasking' effect for ET receptors.5. HUVSMCs synthesize and secrete immunoreactive ET-1, ET-3 and big ET-1, and possess intracellular levels of immunoreactive mature ET and big ET-1. There is some evidence of common cellular mechanisms between growth factors and vasoconstrictor peptides, suggesting a close relationship between contraction and proliferation. Since the development of various vascular pathologies such as atherosclerosis, hypertension and after vessel injury has been attributed to alterations in the normal growth pattern of VSMCs, the role of ET in these diseases may be of significance. PMID- 7881756 TI - Differences between 5-HT3 receptor antagonists in modulation of visceral hypersensitivity. AB - 1. Noxious colo-rectal distension was applied in conscious rats by acute balloon inflation and the effects observed as abdominal muscle contraction with the threshold typically between 10-40 mmHg. The effects of 5-HT3 receptor antagonists on responses to noxious colo-rectal distension were then studied in both normal rats and those pretreated with 5-hydroxytryptophan (5-HTP). 2. Granisetron and ondansetron (10 micrograms kg-1 and 1 mg kg-1, s.c.) had no effect on visceromotor thresholds to colo-rectal distension in normal rats. 3. Hypersensitivity of the colo-rectum was achieved by systemic administration of a low dose of 5-HTP (10 mg kg-1, s.c.) which lowered the distension pressure required to induce the visceromotor reflex; analysis of variance showed a highly significant treatment effect (F1,11 = 84.26, P < 0.001). 4. Granisetron, zatosetron, bemesetron and renzapride equi-potently increased the threshold values at which distension evoked a visceromotor reflex after dosing with 5-HTP, with a maximal response 3.6 to 4.2 fold above saline controls, at 10 micrograms kg-1, s.c. Metoclopramide (10 micrograms kg-1) also raised the level of distension required to elicit a response. By comparison, tropisetron caused a small, non-significant increase in visceromotor threshold values and only at high doses (1 mg kg-1), whilst ondansetron and BRL 46470 had no significant effects at doses up to 10 mg kg-1. 5. The response to granisetron (10 micrograms kg-1, s.c.) in 5-HTP-treated rats was unaltered by pre-administration of naloxone (5 mg kg-1, s.c.). 6. These results suggest that a 5-HT3-like receptor modulates 5-HTP- evoked visceral hypersensitivity.However, the rank order of antagonist potency does not correlate with their order of potency against the classically defined 5 HT3 receptor. PMID- 7881757 TI - Platelet-derived growth factor receptor expression after neural grafting in a rat model of Parkinson's disease. AB - Platelet-derived growth factor (PDGF) has trophic effect on dopaminergic neurons in vitro. We have previously shown dynamic changes in the expression of PDGF in embryonic mesencephalic grafts and surrounding host striatal tissue following intracerebral transplantation in a rat model of Parkinson's disease. In this study the expression of the PDGF receptors was examined in the same model using immunohistochemistry. Most ventral mesencephalic (VM) cells from E13-E15 rat embryos possessed both PDGF alpha- and beta-receptors before implantation. Double immunofluorescence staining revealed that about 10% of the cells also expressed tyrosine hydroxylase (TH). The PDGF alpha-receptor was detectable in the graft up to 1 wk after transplantation but had disappeared at 3 wk. In the host tissue, scattered glial cells were positive for the alpha-receptor but the expression was unchanged following transplantation. The beta-receptor expression almost completely disappeared from the grafted tissue by 4 h following transplantation, and only a few cells of the host striatum showed immunoreactivity. However, after 3 wk beta-receptor positive cells were again detectable in the graft. These cells appeared to be endothelial cells as identified by an antibody against von Willebrand's factor. Our data suggest that PDGF might act locally on embryonic dopaminergic cells in an autocrine or juxtacrine manner before and shortly after transplantation, and on surrounding glial cells in a paracrine manner after transplantation. Furthermore, PDGF-BB might influence neovascularization in the graft. PMID- 7881758 TI - Human embryonic retinal cell transplants in athymic immunodeficient rat hosts. AB - This study investigates the possibility to use the athymic "nude" rat as a host for the transplantation of human embryonic retinal cells without immunosuppression. The long-term development of such transplants is compared with results from our earlier study that used immunosuppressed rats, and showed transplant immunoreactivity for S-antigen. Several additional cell markers have been included: rhodopsin, rod (alpha-transducin, neuron-specific enolase (NSE), synaptophysin (SYN), cone-specific opsins, vimentin, cellular retinaldehyde binding protein (CRALBP), glial fibrillary acidic protein (GFAP), rat major histocompatibility antigen class II (MHC-II) and a rat macrophage marker (Ox-42). Human retinal cells (9-13 wk postconception) were transplanted to the eyes of 28 athymic rats. Host rats were kept in microisolator cages for up to 48 wk after surgery. Host immune response and the development of the transplants were studied using histology, immunohistochemistry and electron microscopy. When using retinas of donors 9-11 wk postconception, transplants grew to 2-3 mm in diameter with many rosettes, in 31 of 35 eyes. Transplants derived from donors 12-13 wk postconception did not survive as well (8 out of 11 eyes), were smaller and less organized. All transplants fused well with the host retina, better than corresponding transplants to immunosuppressed rat hosts. Most transplants appeared to be healthy, even after long survival times, and only occasionally were MHC-II positive macrophages observed in transplants or host retinas. All retinal layers were observed, except for an inner limiting membrane on the vitreous surface. The oldest transplants (34-57 wk total age = donor age + time after surgery) exhibited well developed photoreceptors, rods and cones, with inner and outer segments. SYN-staining showed the development of inner and outer plexiform layers. Although many cones stained for SYN and NSE, few were immunoreactive for red-green or blue opsin. Most rods became immunoreactive for S antigen and rhodopsin. Transplant Muller cells stained for vimentin and CRALBP. Immunoreactivity for GFAP developed slowly and was not completely expressed in all transplant Muller cells until 44 wk total age. Nude rats offer an excellent model for the study of human retinal xenografts without the negative effects of immunosuppression. Compared to immunosuppressed rats, transplantation to nude rats gives consistent results and superior long-term survival of hosts and transplants. PMID- 7881759 TI - Human fetal cortical tissue fragments survive grafting following one week storage at +4 degrees C. AB - Grafting of human fetal tissue fragments has been used successfully in experimental and clinical trials. The development of techniques to store human fetal tissue fragments for longer time periods would allow to establish temporary tissue banks. We dissected several human cortical tissue fragments from one fetus and tested different storage conditions (cooling, freezing, culturing). After storage, the tissue fragments were transplanted into cavities in the cortex of host rats and the volume of the surviving grafts calculated. We report that human cortical tissue fragments grafted immediately after dissection (control group) or grafted after storage for 3 h in cryopreservation medium at room temperature survived grafting and resulted in graft sizes of 102 +/- 26 mm3 and 242 +/- 210 mm3, respectively, however, statistically not different. When the human cortical tissue fragments were slowly frozen and stored for 1 wk and/or when the fragments were cultured for 1 week in culture medium using a roller tube technique, grafts did not survive under our conditions. However, when the human cortical tissue fragments were stored for 1 week at +4 degrees C in cryopreservation medium, the graft size (48 +/- 24 mm3) was reduced but statistically not different from the control group. We conclude that human cortical tissue fragments can be stored at +4 degrees C for at least 1 wk without major loss of ability to survive grafting. PMID- 7881760 TI - Mechanical stress-induced orientation and ultrastructural change of smooth muscle cells cultured in three-dimensional collagen lattices. AB - The effect of tensile stress on the orientation and phenotype of arterial smooth muscle cells (SMCs) cultured in three-dimensional (3D) type I collagen gels was morphologically investigated. Ring-shaped hybrid tissues were prepared by thermal gelation of a cold mixed solution of type I collagen and SMCs derived from bovine aorta. The tissues were subjected to three different modes of tensile stress. They were floated (isotonic control), stretched isometrically (static stress) and periodically stretched and recoiled by 5% above and below the resting tissue length at 60 RPM frequency (dynamic stress). After incubation for up to four wk, the tissues were investigated under a light microscope (LM) and a transmission electron microscope (TEM). Hematoxylin and eosin-stained LM samples revealed that, irrespective of static or dynamic stress loading, SMCs in stress-loaded tissues exhibited elongated bipolar spindle shape and were regularly oriented parallel to the direction of the strain, whereas those in isotonic control tissues were polygonal or spherical and had no preferential orientation. In Azan stained samples, collagen fiber bundles in isotonic control tissues were somewhat retracted around the polygonal SMCs to form a random network. On the other hand, those in statically and dynamically stressed tissues were accumulated and prominently oriented parallel to the stretch direction. Ultrastructural investigation using a TEM showed that SMCs in control and statically stressed tissues were almost totally filled with synthetic organelles such as rough endoplasmic reticulums, free ribosomes, Golgi complexes and mitochondria, indicating that the cells remained in the synthetic phenotype. On the other hand, SMCs in dynamically stressed tissues had increased fractions of contractile apparatus, such as myofilaments, dense bodies and extracellular filamentous materials equivalent to basement membranes, that progressed with incubation time. These results indicate that periodic stretch, in concert with 3-D extracellular collagen matrices, play a significant role in the phenotypic modulation of SMCs from the synthetic to the contractile state, as well as cellular and biomolecular orientation. PMID- 7881761 TI - Immune privilege of the testis for islet xenotransplantation (rat to mouse). AB - The testis has been suggested as an immune privileged site for islet transplantation. The present study evaluated this hypothesis by transplanting islets from Wistar Furth rats into (a) the testes; (b) the subcapsular space of the kidneys; or (c) the cryptorchid abdominal testes of streptozotocin-induced diabetic Swiss ND4 mice. Transplantation of 800 rat islets into the cryptorchid testes normalized blood glucose for 9.3 +/- 1.4 (Mean +/- SD) days, not significantly different from that of the scrotal testis site (12.4 +/- 1.3), or when the subcapsular space of the kidneys was used (11.5 +/- 1.2). When mouse islets were isotransplanted into the cryptorchid testes of diabetic mice, normoglycemia was maintained for the entire 3 month study period. Histologic examination of the islet xenograft-bearing cryptorchid testes at day 7 post transplantation and 2 days after returning to hyperglycemia revealed lymphocyte infiltration surrounding and inside the graft. No lymphocyte infiltration was seen in the isograft bearing-testes at 3 mo after transplantation. Cyclosporine A (CsA, 15 mg/kg/day) administration to the islet xenograft recipient slightly prolonged the normoglycemic period to 13.7 +/- 1.8 days (p < 0.01). Increasing CsA dose to 25 mg/kg induced a 66% (4/6) mortality, and did not further prolong the normoglycemic period. Using a lower number of rat islets (200 or 400 islets), prolonged graft survival was achieved in some (4 out of 20) animals when the cryptorchid testis was used. In contrast, transplantation of 400 rat islets into the subcapsular space of the kidneys was not associated with prolonged graft survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881762 TI - Immunocytochemical detection and characterization of intrahepatic human pancreatic islets after combined liver-islet allotransplantation. AB - The unique availability of an explanted liver-islet allograft, removed for primary nonfunction of the liver, led us to evaluate distribution and phenotype of exocrine and endocrine components of the pancreatic graft. Immunocytochemistry was used to map patterns of gene products for islet hormones, proprotein processing enzymes, panneuroendocrine markers, and pancreatic exocrine markers. When compared with age-matched control pancreases, insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-producing cells were similarly represented and distributed within the grafted islet. We also demonstrate that the intrahepatic transplanted islets retained the enzyme machinery able to process the hormone precursors into bioactive fragments. In the clinical setting, this resulted in an immediate functioning of the graft and insulin-independence of the patient one month after transplantation. The purity in islets, as assessed by immunocytochemistry with antibodies to tissue constituents of endocrine and exocrine lineages, was around 40%. Despite the massive intraportal presence of pancreatic acinar tissue, no signs or symptoms attributable to ectopic hypersecretion of exocrine enzymes occurred. In fact, when tested with antibodies to such enzymes, low levels of immunoreactivity were observed in the grafted acinar cells. PMID- 7881763 TI - A device to measure the oxygen uptake rate of attached cells: importance in bioartificial organ design. AB - Quantification of the dependence of cellular oxygen uptake rate (OUR) on oxygen partial pressure is useful for the design and testing of bioartificial devices which utilize cells. Thus far, this information has only been obtained from suspended cells and from cells attached to microcarriers. In this work, a device was developed to obtain the dependence of OUR on oxygen partial pressure for anchorage-dependent cells cultured in standard culture dishes. The device is placed and sealed on the top of the culture dish, and holds a Clark polarographic mini-electrode flush with the bottom surface of the device. It also houses a motor to spin a magnetic stir bar within the cell chamber to insure that the medium is well-mixed. Several characteristics of the device--such as oxygen leakage into the device chamber, electrode-lag time, and linearity of the electrode at low oxygen partial pressures--were quantified and their potential effect on the values of Vm (maximal OUR) and K0.5 (oxygen partial pressure at which OUR is half-maximal) were evaluated. Comparison of Vm and K0.5 values obtained with this device with previously published values for suspended rat hepatocytes, Bacillus cereus, and E. coli indicated that the technique provides values accurate within 30% as long as the cell under study has a K0.5 greater than approximately 1.0 mmHg. For hepatocytes cultured on 0.05 mm thickness collagen gel for 1 day (n = 4) and 3 days (n = 6), Vm was found to be 0.38 +/- 0.12 and 0.25 +/- 0.09 nmol O2/S/10(6) cells, respectively, and K0.5 was found to be 5.6 +/- 0.5 and 3.3 +/- 0.6 mmHg, respectively. This technique should aid in predicting bioreactor conditions such as flow rate, cell density, distance of cell from flow, and gas phase oxygen partial pressure which can lead to oxygen limitations. In addition, further studies of the effect of factors such as extracellular matrix composition, metabolic substrate, and drugs on the dependence of OUR on oxygen partial pressure for many anchorage-dependent cell types can be pursued with this technique. PMID- 7881764 TI - In vitro reconstruction of hybrid arterial media with molecular and cellular orientations. AB - A hybrid medial tissue composed of a type I collagen gel, into which smooth muscle cells (SMCs) derived from bovine aortic media were 3-dimensionally (3D) embedded, was constructed around an elastomeric silicone tube (outer diameter: 8 mm). Subsequently, hybrid tissues thus prepared were subjected to three modes of mechanical stimulation in the medium: one was subjected to flotation with no disturbance (isotonic control), the second was kept isometrically (static stress) and the third was subjected to continuous periodic stretch by inflation of the embedded silicone tube which stimulated arterial pulsation (dynamic stress, amplitude: 5% in inner diameter; frequency: 60 RPM). After a 5-day culture period, hybrid tissues were morphologically investigated. In control gels, polygonal SMCs and extracellular collagen fiber bundles were randomly oriented. On the other hand, upon static or dynamic stress loading, bipolar spindle-shaped SMCs and dense collagen fiber bundles were aligned circumferentially around the silicone tube, which proceeded with time. The orientations of SMCs and collagen fibers were more prominent in dynamically stressed hybrid tissues than those in statistically stressed ones. The pulsatile stress-loaded hybrid medial tissue mimicked the media of native muscular arteries in terms of cellular and molecular orientations. PMID- 7881765 TI - All-trans retinoic acid induces functional maturation of epidermal Langerhans cells and protects their accessory function from ultraviolet radiation. AB - Retinoids provide some protection against ultraviolet radiation-induced skin damage. We have previously shown that topical all-trans retinoic acid prevents ultraviolet light from reducing the density of epidermal Langerhans cells in the epidermis but does not inhibit the development of immunosuppression to a locally applied contact sensitizer. We therefore investigated the ability of all-trans retinoic acid to modulate Langerhans cell induction of allogeneic T-cell proliferation in the mixed epidermal cell lymphocyte reaction. Langerhans cells isolated from all-trans retinoic acid-treated mice induced an enhanced mixed epidermal cell lymphocyte reaction. This is similar to Langerhans cells cultured with granulocyte-macrophage colony stimulating factor. Retinoic acid treatment also enhanced the allogeneic cell-stimulating capability of Langerhans cells isolated from ultraviolet-irradiated mice. Langerhans cells from all-trans retinoic acid-treated, ultraviolet-irradiated mice which were "matured" by 3 days in culture induced a larger mixed epidermal cell lymphocyte reaction than mice treated with solvent and ultraviolet irradiation. Thus all-trans retinoic acid treatment of mice causes Langerhans cell maturation and inhibits ultraviolet light from reducing their density or impairing their allogeneic cell-stimulating capacity. However, these mice remained immunosuppressed upon application of a contact sensitizer to irradiated or unirradiated skin. It is thus likely that, whereas all-trans retinoic acid protects local Langerhans cell numbers and function, it does not inhibit the production of an ultraviolet radiation-induced photoproduct which causes immunosuppression. PMID- 7881766 TI - Retinoic acid induces expression of PA-FABP (psoriasis-associated fatty acid binding protein) gene in human skin in vivo but not in cultured skin cells. AB - PA-FABP (psoriasis-associated fatty acid-binding protein) is a new member of a group of low-molecular-weight proteins that are highly up-regulated in psoriatic skin and that share similarity to fatty acid-binding proteins. In this study we demonstrate that PA-FABP transcripts are expressed in human skin in vivo and that topical application of 0.05% retinoic acid (RA) cream results in a rapid induction of PA-FABP transcripts following treatment for 16 hours and persists at increasing levels after 48 and 96 h of RA treatment. The PA-FABP mRNA response to RA was reduced by approximately 50% when patients concurrently were treated with RA and 0.025% clobetasol propionate (CLO) for 48 and 96 h, whereas treatment with CLO alone resulted in PA-FABP transcript levels not significantly different from vehicle-treated skin. When comparing the effects of a well-known irritant, sodium lauryl sulfate (SLS), to those of RA and its vehicle, 0.05% RA cream but not 2% SLS in RA vehicle caused PA-FABP mRNA induction after 16 h. SLS treatment of human skin for 96 h caused a slight increase in PA-FABP transcripts, but markedly less than that observed in response to RA treatment. Incubation of cultured human keratinocytes or skin fibroblasts with RA for up to 48 h did not significantly induce PA-FABP transcripts. Expression of PA-FABP message in keratinocytes was observed to be induced by calcium and fetal calf serum (FCS), while tetra decanoyl phorbol acetate (TPA) caused little or no induction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881767 TI - Quantitative assessment of melanoma single-cell motility in vitro. AB - Cell motility is a crucial property of tumor cells during invasion and metastasis. In this study we developed a computer assisted system to measure translocation and stationary motility of single cells and used this procedure to evaluate the influence of cytochalasin A (CA) on single-cell motility parameters of K1735-M2 mouse melanoma cells. The cells were seeded at low density into a microincubator. Time lapse microcinematography was performed every 20 seconds from a high power field to assess stationary motility and every 10 minutes with a screening objective to measure translocation. 1 muMol CA was added to the medium 48 hours before measurement. Calculation of stationary motility was performed by subtraction of subsequent images and the resulting image difference was used for quantitative evaluation. Three different measuring windows were drawn to discriminate between membrane ruffling, intracellular organelle transport and overall stationary motility. For each cell we measured change of density (CD), area of change (AC), perimeter of area of change (PC), area of ruffling (AR), number of ruffling sites (NR), change of intracellular organelles (CIO) and number of changing intracellular organelles (NIO). In order to quantify translocation, the center of gravity of each cell was assessed subsequently and the velocity was calculated by connecting the centers of gravity. CA-treated cells showed a significantly lower stationary motility and membrane ruffling compared to the untreated cells (U-test: p < = 0.01), but there was not significant difference concerning the intracellular organelle transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881768 TI - Humoral immunity to Malassezia furfur serovars A, B and C in patients with pityriasis versicolor, seborrheic dermatitis and controls. AB - This study examined the humoral immune responses to Malassezia furfur serovars A, B and C of 10 patients with pityriasis versicolor, 10 patients with seborrheic dermatitis and 20 age- and sex-matched controls. A transferable solid-phase ELISA was used to determine titres of total Igs, IgM, IgA and IgG specific to M. furfur serovars A, B and C. The results demonstrated that patients with seborrheic dermatitis had a significantly higher titre of total Igs to serovar A than patients with pityriasis versicolor; and that patients with seborrheic dermatitis had a significantly higher titre of IgA to serovar C than patients with pityriasis versicolor. The titres of total Igs for controls and patients with seborrheic dermatitis were significantly lower to serovar B than to serovar C. A modified TSP ELISA was used to determine the titres of the IgG subclasses. Titres of IgG1,3,4 to serovar B were significantly higher in seborrheic dermatitis patients than pityriasis versicolor patients and titres of IgG3 to serovar A were significantly higher in seborrheic dermatitis patients than pityriasis versicolor patients. However, despite the differences between the patient groups, none of these results was significantly different to those of controls. Thus, this study did not demonstrate any differences in humoral immunity of patients suffering from Malassezia-associated dermatoses when compared to normal controls. These results may suggest that the humoral immune response to M. furfur is not related to the pathogenesis of Malassezia-associated dermatoses, but simply to the carriage of M. furfur on the skin. PMID- 7881769 TI - Skin changes in patients claiming to suffer from "screen dermatitis": a two-case open-field provocation study. AB - An open-field provocation, in front of an ordinary TV set, of 2 patients regarding themselves as suffering from skin problems due to work at video display terminals (VDTs) is presented. Using immunohistochemistry, in combination with a wide range of antisera directed towards cellular and neurochemical markers, we were able to show a high-to-very high number of somatostatin-immunoreactive dendritic cells as well as histamine-positive mast cells in skin biopsies from the anterior neck taken before the start of the provocation. At the end of the provocation the number of mast cells was unchanged; however, the somatostatin positive cells had seemingly disappeared. The reason for this latter findings is discussed in terms of loss of immunoreactivity, increase of breakdown, etc. The high number of mast cells present may explain the clinical symptoms of itch, pain, edema and erythema. Naturally, in view of the present public debate, the observed results are highly provocative and, we believe, have to be taken seriously. PMID- 7881770 TI - Nerve growth factor increases the mitogenicity of certain growth factors for cultured human keratinocytes: a comparison with epidermal growth factor. AB - Newborn foreskin and adult skin keratinocytes (KTs) were cultured in 24-well plates using keratinocyte basal medium (KBM) either alone or supplemented with epidermal growth factor (EGF) or nerve growth factor (NGF), plus one of the following: insulin (INS), insulin-like growth factors (IGF)-1 or -2, transforming growth factor alpha (TGF alpha), basic fibroblast growth factor (bFGF). Culture was maintained until one group of cells reached about 30,000 cells/well, when cells were stained with crystal violet and the extracted dye used to quantify cell numbers. In some cases, cells were subjected to the hexosaminidase assay for enumeration. In KBM alone, EGF, IGF-1, IGF-2 and TGF alpha were mitogenic to newborn KTs. In addition, NGF increased the growth of adult KTs, possibly by mechanisms involving synergy with autocrine growth factors. EGF augmented the growth of newborn cells in the presence of each of the growth factors except TGF alpha, but adult cells exhibited only additive effects. In the presence of IGF-1 or IGF-2, NGF stimulated the growth of both newborn and adult cells by as much as 150% above purely additive increases in cell numbers. NGF amplifies the effects of most neurotrophic factors that are also KT mitogens and may therefore be significant in psoriatic lesions, where many of these factors are overexpressed, and in wound healing, in promoting KT growth. PMID- 7881771 TI - Consent to treatment during childhood. The assessment of competence and avoidance of conflict. PMID- 7881772 TI - Psychological debriefing and prevention of post-traumatic stress. More research is needed. PMID- 7881773 TI - Syndromes of schizophrenia. Classic literature. PMID- 7881774 TI - Extrapyramidal symptoms with selective serotonin reuptake inhibitors. AB - BACKGROUND: Several case reports in the literature suggest that selective serotonin reuptake inhibitors can produce extrapyramidal symptoms. METHODS: Computerised literature searches were used to identify reports on extrapyramidal symptoms and serotonin reuptake inhibitors. Subsequently, manual searches were made for articles in which there was any indication of the mechanisms responsible for these extrapyramidal symptoms. RESULTS: Only a few reports could be identified in which serotonin reuptake inhibitors were implicated in extrapyramidal symptoms in some patients. CONCLUSIONS: Evidence is discussed from preclinical and clinical studies suggesting the interaction between serotoninergic and dopaminergic neurotransmitter system, as a possible mechanism for production of extrapyramidal symptoms. PMID- 7881775 TI - Inner london collaborative audit of admissions in two health districts. I: Introduction, methods and preliminary findings. AB - BACKGROUND: There is pressure on acute admission services in inner-city areas. Two deprived London districts with markedly different acute bed ratios but similar sociodemographic backgrounds were compared to test the hypothesis that more facilities mean better service. METHOD: An instrument for auditing the use of short-stay hospital beds was constructed to collect information concerning admissions to, and short-stay patients in, the chosen districts during a three month period. RESULTS: There was a higher admission rate and substantially greater use of beds per unit population in south Southwark than in Hammersmith & Fulham. Much of the difference was attributable to a higher rate of admission of patients with affective disorders in south Southwark. CONCLUSIONS: The results are not explained by variations in population need, longer in-patient stay, or poorer aftercare leading to early relapse. The question of whether there is over provision of services compared with real need in south Southwark, or under provision (particularly for people with affective disorders) in Hammersmith & Fulham, is considered but left open for discussion following a study of ethnic issues and the reasons for admission. PMID- 7881776 TI - Inner London collaborative audit of admissions in two health districts. II: Ethnicity and the use of the Mental Health Act. AB - BACKGROUND: Twenty-six per cent of patients in two Inner London districts were admitted to acute wards under the provisions of the Mental Health Act. Compared with those not under compulsion, they were young, male, more likely to be of black Caribbean origin, and to have a diagnosis of schizophrenia of short duration. The hypothesis is tested that ethnicity determines rates of compulsory admission independently of the other factors. METHOD: Sampling and data collection methods were described in the first paper. Statistical analyses included a log-linear analysis of six key variables: compulsory admission, challenging behaviour, diagnosis, ethnicity, age, and sex. RESULTS: There were no substantial differences between districts. Analysis provided two similar statistical models. In both, admission under the Act was strongly associated with challenging behaviour and diagnosis of schizophrenia. In the model of best fit there was no significant interaction term for ethnicity and compulsion. In the second model there was a weak association. CONCLUSIONS: Ethnicity did not appear to be of outstanding importance in decisions to use the Mental Health Act. There was a strong link between ethnicity and diagnosis, independent of compulsion. Differences between the districts made no major contribution to the rates of compulsory admission. PMID- 7881780 TI - Post-mortem antipsychotic drug concentrations and unexplained deaths. AB - BACKGROUND: The relationship between antipsychotic drug treatment and sudden unexplained death remains unclear. The estimation of post-mortem blood drug concentrations should be helpful. METHOD: Eight medico-legal cases were reviewed with respect to behaviour of patient, type and dosage of drug treatment, mode of death, post-mortem findings and drug concentrations. RESULTS: The problems of evaluating such drug levels are discussed. Five of the eight patients had probably toxic concentrations of antipsychotic and/or antidepressants, which caused death, usually involving cardiac arrhythmias. CONCLUSIONS: In cases of sudden unexpected death, a sample of blood from a peripheral vein should be obtained immediately death is pronounced or the body discovered, and sent for analysis. To minimise such fatalities, the patient should be monitored carefully, with ECG if feasible, and electrolyte balance checked. The drug regimen used should be kept simple and large doses of antipsychotics and/or antidepressants avoided wherever possible. PMID- 7881777 TI - Inner london collaborative audit of admission in two health districts. III: Reasons for acute admission to psychiatric wards. AB - BACKGROUND: In this series, rates of admission and daily bed use in south Southwark were 30% higher than in Hammersmith & Fulham, principally because of a higher rate of admission for affective disorders. Factors associated with compulsory admission did not differ between the districts. This final paper examines the severity of symptoms, the reasons given for admission and factors relevant to the judgement to admit, in order to test the hypothesis that more resources mean better service. METHOD: Sampling and data collection methods were described in the first paper. RESULTS: In both districts, major reasons for admission were self-neglect and risk of self-harm, poor adaptive functioning, and poor acceptance of medication. In south Southwark, a group of patients had affective disorders and less severe symptoms but a stated risk of suicide. Rates for, and severity of, schizophrenia were similar in the two districts. Social and preventive reasons for admission were given more frequently in south Southwark, where patients had more often been in contact with services before admission. Staff there, but not in Hammersmith & Fulham, suggested that many could have benefited from alternative forms of residential care. CONCLUSIONS: A 'buffer' of hospital beds in south Southwark may have allowed a more acceptable service, particularly for affective disorders. The possibility that this buffer could be replaced by a wider range of residential accommodation, including hostels away from the District General Hospital, is discussed. Ten recommendations are listed. PMID- 7881779 TI - Adolescent girls. II. Background factors in anxiety and depressive states. AB - BACKGROUND: This study investigated the prevalence and background variables associated with anxiety and depressive disorders occurring in a community population of older teenage girls. METHOD: Girls aged 15-20 years (n = 529) whose names were drawn from general practitioner age/sex registers completed self report Great Ormond Street Mood Questionnaires. From this sample, 143 girls (69 with high self-report scores and 74 controls) were intensively interviewed. Information was obtained on confiding/supportive relationships, family arguments and rows, quality of marital relationship, and degree of parental control. Psychiatric state was assessed by use of the Clinical Interview Schedule to provide a Total Weighted Score. A modified form of the Bedford Life Events and Difficulties Schedule was applied. RESULTS: The estimated one-year prevalence rate for psychiatric disorder was 18.9%, and 16.9% for depression and anxiety disorders. Using a logit analysis, it was shown that maternal distress (P < 0.02) and the quality of the mother's marriage (P < 0.02) were independently associated with the presence of depression and anxiety disorders. CONCLUSIONS: About 17% of girls in a community sample living at home showed a depression or anxiety disorder. Even in late adolescence, the presence of a mood disorder is closely linked to the quality of family relationships within the home. PMID- 7881778 TI - Adolescent girls. I. Self-reported mood disturbance in a community population. AB - BACKGROUND: This study was undertaken to fill gaps in our knowledge of the rate of mood disorder in teenage girls in transition from school to further education, employment or unemployment. METHOD: Girls aged 15-20 years (n = 529) whose names were drawn from general practitioner age/sex registers were interviewed at home and completed the Great Ormond Street Mood Questionnaire. Their mothers completed the 28-item General Health Questionnaire (GHQ). Social background variables were obtained. RESULTS: Of the girls, 20.8% scored over the cut-off point previously established to indicate risk of psychiatric disorder. Scoring over the cut-off point was not associated with age or parental social class. It was associated with parental separation/divorce (P < 0.004), with maternal self-report on the GHQ (P < 0.001), and with parental unemployment (P < 0.04). Lowest self-report scores were obtained by girls who had left school and were in employment (P < 0.01). CONCLUSIONS: About one in five of girls aged 15-20 are at risk of affective disorder. Self-reported mood disturbance is associated with a wide range of social and familial background variables, but not with age or parental socioeconomic status. PMID- 7881782 TI - Outcome of deliberate self-poisoning. An examination of risk factors for repetition. AB - BACKGROUND: One of the most important outcomes following an episode of non-fatal deliberate self-poisoning is its repetition. METHOD: In a prospective follow-up study the subjects were 992 people responsible for 1096 consecutive episodes of deliberate self-poisoning recorded at a teaching hospital accident and emergency department. Risk factors examined were socio-demographic variables, psychiatric and self-harm history, aspects of the self-poisoning episode, and appearance and behaviour at accident and emergency; the frequency of each was compared between those patients who repeated within one year (n = 116) and those who did not (n = 876). RESULTS: Those who repeated were more likely to have ingested more than one drug, to report a previous episode of self-poisoning, to be aged 25-54, and to have experienced previous psychiatric care or psychiatric admission. They were less likely to be in paid employment, or to have expressed a threat to another person or written a note. The best predictor--previous psychiatric contact--only had a positive predictive value of 21% (95% confidence interval 16-25%). CONCLUSIONS: Risk factors for repetition of self-poisoning should be kept up-to date despite modest predictive power. More attention might be paid to clinical rather than socio-demographic aspects of self-harm. PMID- 7881781 TI - Comparison of long-term benzodiazepine users in three settings. AB - BACKGROUND: Most studies of chronic benzodiazepine users consider selected populations which may be unrepresentative. This study was undertaken to examine possible differences between groups. METHOD: Subjects chosen were benzodiazepine users in general practice, a hospital clinic, and attending TRANX trials. Descriptive data were collected on characteristics and outcome. RESULTS: TRANX trial patients had the best outcome (P = 0.027). Hospital cases used high doses of anxiolytic benzodiazepines; concomitant mental disorder, including schizophrenia, was common. General practice cases were older and mainly used hypnotics (P < 0.05). CONCLUSIONS: Because groups of benzodiazepine users are different, there cannot be one single management approach. Cases require individual medical assessment. PMID- 7881783 TI - Coping with chronic pain. Some patients suffer more. AB - BACKGROUND: A multi-dimensional approach was used to examine coping in chronic pain. The following hypotheses were tested: (a) patients who cope maladaptively also cope generally in a similar way; (b) patients' maladaptive coping is associated with childhood adversity. METHOD: Cross-sectional and retrospective data were collected from 68 consecutive patients (aged 18-70) at a pain clinic where their disease was non-systemic and the pain had lasted for at least three months. Sixty-one patients were interviewed using the Structured Clinical Interview for DSM-III-R, and the Measure of Parental Care in Childhood. All patients completed questionnaires on their pain and personality. RESULTS: Two coping styles emerged from factor analysis. One was associated with chronicity, psychiatric morbidity, harm avoidance, immature defence style and reporting parental indifference. CONCLUSION: Patients may be predisposed to cope maladaptively after the experience of parental indifference in early life. Such coping is likely to reflect more general patterns. PMID- 7881784 TI - Autoscopic phenomena. AB - BACKGROUND: Autoscopy is defined here as a visual experience where the subject sees an image of him/herself in external space, viewed from within his/her own physical body. This paper reviews the literature both historically and conceptually, and includes a quantitative study of accumulated cases. METHOD: Cases published since 1935 and meeting the above definition for autoscopy (n = 53) were included, together with three personally-observed patients. A clinical protocol was completed for each case, including information about the autoscopic image. Cases were compared using non-parametric statistics on dichotomised variables. RESULTS: There were 38 men and 18 women, with a mean age of 39.5 years (range 13-78). Of the subjects, 33 (59%) had a neurological illness, most frequently epilepsy (18 cases). Right and left sided lesions were equally represented. Psychiatric disorder was often present (33 cases, 59%), most commonly delirium, depression or psychosis. The features of the images seen were diverse, but speaking images were associated with younger age, male sex, psychotic illness, longer duration of image, and hypnagogic/hypnopompic experiences. CONCLUSIONS: Autoscopy may arise from a convergence of several variables, including gender, personality factors, neurological and/or psychiatric disease, exhaustion and dissociation, whose interaction may override the normal inhibition of temporal lobe activity. A cognitive neuropsychological hypothesis is proposed, together with avenues for future research. PMID- 7881785 TI - Formal communication disorder. Sign language in deaf people with schizophrenia. AB - BACKGROUND: This study investigates whether anomalies in the sign language of prelingually deaf schizophrenics can be elicited and described systematically. METHOD: Thirty schizophrenic and seven manic adults were recruited on the basis of a British Sign Language (BSL) version of the Present State Examination. Thirty seven controls were matched for sex, age and ethnicity. Each participant became deaf before the age of two, and uses BSL as the primary means of communication. RESULTS: Analysis reveals: (a) anomalies which are similar to those occurring in the spoken language of hearing schizophrenics; and (b) another series which is closely related to the life experience of deaf subjects and to the visuo-spatial medium itself. CONCLUSIONS: There is evidence that formal communication disorder does occur in sign language. This has implications for more efficient diagnosis and management of deaf persons presenting to psychiatric services, as well as for the mechanisms of schizophrenic symptomatology itself. PMID- 7881786 TI - Survival analysis and readmission in mood disorder. AB - BACKGROUND: This is an exploratory study of readmission in mood disorder. METHOD: The study is naturalistic and employs survival analysis. We identified 821 individuals with ICD-9 diagnoses, drawn from the Tasmanian Mental Health Register. RESULTS: No demographic variables influence the time to readmission. Two groups emerge: those with affective psychoses, and those with neurotic depression, brief depressive reaction and depressive disorders not elsewhere classified. The former group demonstrated shorter times to readmission than the latter. There was no support for a unipolar-bipolar distinction. CONCLUSIONS: Affective psychoses have a less favourable outcome than expected. There was support for an endogenous-neurotic distinction. PMID- 7881787 TI - Depot antipsychotics in the prophylaxis of bipolar affective disorder. AB - BACKGROUND: The efficacy of depot antipsychotic drugs in the prophylaxis of bipolar affective disorder was investigated. METHOD: Life charts were constructed for 18 outpatients with bipolar disorder receiving prophylactic treatment with depot medication. The durations of affective episodes were compared during periods on or off medication. RESULTS: The subjects suffered fewer relapses and spent significantly less time in hospital (P = 0.001) for treatment of manic, depressive and mixed affective illness during treatment with depot antipsychotics. CONCLUSIONS: Depot antipsychotic medication may be a useful prophylactic treatment for certain patients with bipolar affective disorder. PMID- 7881788 TI - The Salford Family Intervention Project: relapse rates of schizophrenia at five and eight years. AB - BACKGROUND: This study assessed the long-term effects of family intervention on schizophrenic relapse. METHOD: Forty schizophrenic patients who had participated in a family intervention trial and who had not experienced relapse at two years after discharge from the index admission were traced through case notes and hospital records. The percentage of patients experiencing a relapse was estimated for patients in the family intervention group, the high-EE control group, and the low-EE control group, at five years and eight years after discharge. RESULTS: There were significantly fewer relapses in the family intervention group than in the high-EE control group at both five years and eight years. The number of relapses in the low-EE control group was lower than in the high-EE control group, but this just failed to reach significance. CONCLUSIONS: The benefit of family intervention and the predictive power of EE are sustained over eight years. PMID- 7881789 TI - Prenatal influenza and schizophrenia. PMID- 7881790 TI - Night terrors. PMID- 7881791 TI - Selective serotonin reuptake inhibitors and mania. PMID- 7881792 TI - Psychopathology and 'ecstasy'. PMID- 7881793 TI - Cognitive therapy. PMID- 7881794 TI - Childhood abuse and psychosis. PMID- 7881795 TI - Community psychiatric nurse teams. PMID- 7881796 TI - Impact of new long-stay patients. PMID- 7881797 TI - Capgras, Fregoli and Cotard's syndromes and Koro in folie a deux. PMID- 7881798 TI - Social and community psychiatry. PMID- 7881799 TI - Characterization of the swine adipocyte A1 adenosine receptor using an optimized assay system. AB - The radioligand binding assay of A1 adenosine receptors in adipocyte crude plasma membrane from Yucatan miniature swine was optimized by evaluating 17 factors involved in the assay. Significant effects of CHAPS, adenosine deaminase, EDTA, pre-rinsing glass fiber filters and pH were found for the binding measurements. Using the optimized procedure, [3H]8-cyclopentyl-1,3-dipropylxanthine, ([3H] DPCPX) binding to A1 adenosine receptors in swine subcutaneous adipocyte crude plasma membrane was measured; Bmax and Kd values were 479 +/- 77 fmol/mg protein and 0.87 +/- 0.10 nM, respectively. Values for mesenteric adipose tissue from sedentary swine and subcutaneous adipose tissue from exercise-trained swine were also measured. PMID- 7881800 TI - Transformation of albumin into melanin by hydroxyl radicals. AB - Bovine serum albumin (BSA) was exposed to hydroxyl radicals generated by the Fenton reaction. The reaction of the BSA solution with hydroxyl radicals resulted in a colour change from clear transparent to dark brown. The reaction was followed spectrophometrically. It was observed that during the reaction of BSA with hydroxyl radicals, a melanin-like absorption spectrum developed. The reaction with ferricyanide and the dark brown BSA solution resulted in the same dark blue-green colour as is typical for melanin. The results suggest that, by the reaction of BSA with hydroxyl radicals, melanin was formed. PMID- 7881801 TI - Characterization of insulin receptor from the muscle of the shrimp Penaeus japonicus (Crustacea: Decapoda). AB - The beta-subunit of the insulin receptor from the muscle of the shrimp Penaeus japonicus exists as multiple subtypes with M(r) of 79,000, 77,000 and 75,000. Only the subunit of M(r) 79,000 is autophosphorylated after the addition of insulin. The autophosphorylation occurred specifically at Tyr residues, as demonstrated by the specific subsequent dephosphorylation by the phosphotyrosyl protein phosphatase from the human placenta. The detergent, Triton X-100, and the metal ion, Mn2+, caused a noticeable enhancement of the autophosphorylation of shrimp insulin receptors from the muscle. Okadaic acid activated the kinase activity of the insulin-stimulated insulin receptor, but not the basal activity of the insulin receptor without the addition of insulin. Further studies comparing the insulin binding of the shrimp insulin receptor in the regulation of kinase activity of the multiple beta-subunit subtypes from the shrimp muscle are under way. PMID- 7881802 TI - RH-3421, a potent dihydropyrazole insecticide, inhibits depolarization-stimulated rises in free [Ca2+] and 45Ca2+ uptake in mammalian synaptosomes. AB - The dihydropyrazole RH-3421 inhibits veratridine- and K(+)-induced rises in synaptosomal free Ca2+ with IC50s of 0.2 and 1 microM, respectively. The K(+) induced rise in free synaptosomal Ca2+, which requires external Ca2+, is also blocked by RH-3421 in the presence of tetrodotoxin. The K(+)-stimulated 45Ca2+ uptake by synaptosomes is unaffected by tetrodotoxin, blocked by cobalt ions and inhibited by RH-3421 both alone (IC50 = 11 microM) and in the presence of tetrodotoxin. RH-3421 does not influence the level of free Ca2+ or basal 45Ca2+ uptake in non-depolarized synaptosomes. The results suggest RH-3421 inhibits voltage-sensitive calcium channels in nerve endings. PMID- 7881803 TI - Effect of misoprostol on the enzyme ontogeny of the rat intestine. AB - The effect of Misoprostol (an analog of PGE1) on the biochemical changes in the small intestine of suckling rats was studied. Misoprostol increases sucrase activities in the proximal and the distal small intestine. Jejunal aminopeptidase N activity is higher in Misoprostol-treated rats than in the control rats. This drug also modifies the relative weight of the small intestine and the mucosal ratio of DNA to RNA. Misoprostol effects appear to be mediated by corticosterone release. PMID- 7881804 TI - Solubilization of neuropathy target esterase and other phenyl valerate carboxylesterases from chicken embryonic brain by phospholipase A2. AB - Membrane-bound neuropathy target esterase (NTE) and associated phenyl valerate carboxylesterases were solubilized from chicken embryo brain by phospholipase A2. Phospholipase A2 from bee or cobra (Naja) venoms were the most effective preparations in solubilizing brain NTE and other phenyl valerate carboxylesterases. Phospholipase C and several proteinases (endoproteinase, pronase E, proteinase K, thermolysin, trypsin) did not solubilize brain membrane bound carboxylesterases but reduced their activity. NTE solubilization by phospholipase A2 did not affect its apparent Km and Vmax for the substrate phenyl valerate or the susceptibility of phenyl valerate carboxylesterases to inhibition by paraoxon and mipafox. NTE thermal stability diminished after the treatment of brain membrane fragments with phospholipase A2. PMID- 7881805 TI - Isolated glomeruli of the Atlantic hagfish Myxine glutinosa as an alternative in vitro model to study glomerular protein metabolism in pharmaco-toxicology of anticancer drugs. AB - This study was designed to validate an alternative in vitro system with isolated glomeruli of the Atlantic hagfish Myxine glutinosa as a model to study alterations in glomerular protein metabolisms in pharmaco-toxicology of anticancer drugs. A morphometric characterization of the glomeruli of Myxine glutinosa reveals a calculated glomerular volume of 180 nl/glomerulus. The glomerular extracellular volume, measured as inulin space, is 38.5 nl/glomerulus. Total glomerular protein content of Myxine glutinosa amounts to 3.56 micrograms/glomerulus and total DNA content to 0.44 microgram/glomerulus. Metabolic properties, estimated as glomerular protein synthesis, are comparable with mammalian glomeruli. The glomeruli of Myxine glutinosa are viable in a tissue culture for up to 12 hr. The incorporation rate of radiolabeled amino acids into glomerular, acid-precipitable proteins is almost identical to that of rats (e.g. Myxine glutinosa 1091 +/- 98 DPM/micrograms DNA vs. rat 1340 +/- 84 DPM/micrograms DNA after 4 hr incubation). To evaluate how nephrotoxic substances affect glomerular metabolism in this model, the anticancer drug Adriamycin (ADR) was used to experimentally induce a glomerular lesion. ADR caused an increase in glomerular protein synthesis in isolated glomeruli of Myxine glutinosa, which is in accordance with data found in rats. Cisplatin, in contrast, known to mainly interfere with tubular integrity, had no effect on glomerular protein synthesis, confirming the specificity of the model. The isolated glomeruli of Myxine glutinosa are suggested as a valid alternative multicellular in vitro system for studying alterations in glomerular metabolism under pharmaco-toxicological conditions and for the evaluation of specific target-cell toxicity of selected nephrotoxins. PMID- 7881806 TI - Identification of the site of mutation within the M2 region of the GABA receptor of the cyclodiene-resistant German cockroach. AB - The DNA and amino acid sequences of the membrane-spanning region of the GABA receptors of the German cockroach have been identified along with information on the nature and the specific site of mutation in the cyclodiene-resistant strains. In this resistant strain, the mutation has occurred at the most conserved, lower M2 cylinder region involving a G to T conversion, resulting in an amino acid change of alanine (GCC) residue to serine (TCC). The site, furthermore, coincides with the most conserved region of all GABA receptor subunits and the expected Cl- transporting segment constituting the innermost surface of the channel opening. The deduced sequence of the German cockroach GABA receptor differs from that of Drosophila mainly in the connecting region between M3 and M4. PMID- 7881807 TI - The enzymatic formation of 1 alpha,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 in the liver of fetal rats. AB - We have confirmed the existence of 25-hydroxyvitamin D3 (25-OH-D3)-1 alpha hydroxylase in the liver of fetal rats, in addition to that in the kidney, by in vitro experiments. The findings are similar to those in the fish liver as reported previously (Takeuchi et al., Life Sci. 32, 275-282, 1991). When [3H]-25 OH-D3 was incubated with liver homogenates of vitamin D-deficient fetal rats, a peak corresponding to [3H]-1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) was observed in the profile of high-performance liquid chromatography (HPLC). The formation of the metabolite was confirmed by thermal isomerization into the pre isomer, binding affinity to the receptor and mass fragmentography. Lineweaver Burk plot analysis of mitochondrial 25-OH-D3-1 alpha-hydroxylase in the liver gave an apparent Km value of approximately 2 microM of 25-OH-D3 and a Vmax value of 0.2 pmol of 1,25(OH)2D3/30 min/mg protein. These findings suggest that the enzyme in the liver disappeared with the growth of the fetus and became predominant in the kidney of mature rats. PMID- 7881809 TI - Endocrine and metabolic responses of intact and hypophysectomized turkey poults given a daily injection of chicken growth hormone. AB - Female turkey poults were hypophysectomized at 4-5 weeks of age. Beginning at 6 weeks of age, 20 hypophysectomized and 20 intact birds received a daily intramuscular injection of natural chicken growth hormone (cGH, 100 micrograms/kg body weight) or vehicle for 12 days. Blood samples were taken from each bird just before injection and 4 hr post-injection at 6 and 12 days of treatment. Hypophysectomy reduced the growth rate of turkey poults to 75% of that of intact controls, significantly reduced carcass protein and ash percentages, and significantly lower plasma concentrations of GH, insulin-like growth factor-I, triiodothyronine, thyroxine, insulin, glucose, triglycerides, and non-esterified fatty acids. Hypophysectomy was without effect on liver GH receptor binding activity, but increased liver 5'-monodeiodinase activity. Daily cGH injection had no effect on the average daily gain of either hypophysectomized or intact poults when compared to vehicle-injected controls over 12 days of treatment. Daily cGH administration increased plasma insulin-like growth factor-I levels in intact and hypophysectomized turkeys, and increased plasma triiodothyronine, insulin, glucose, and triglyceride concentrations in hypophysectomized birds, but not in intact birds. Responses of young turkeys to hypophysectomy and GH replacement were consistent with the known metabolic role of GH in other species, but the influence of GH on growth appears to be of less importance in poultry than in mammals. PMID- 7881808 TI - Immunological and biochemical characterization of cytochromes P-450 in mullet (Mugil cephalus): comparison with rainbow trout P-450s. AB - Immunoblots (Western blot) of mullet liver microsomes revealed the presence of multiple forms of P-450 that appear to be structurally related to rainbow trout CYP1A1 and CYP2K1 and to P-450 LMC1 and LMC4, but not to LMC5. 3 Methylcholanthrene but not beta-naphthoflavone induced a major 58 kDa liver protein and a minor 56 kDa protein in mullet that both cross-reacted with anti trout CYP1A1 IgG. The levels of immunodetectable P-450s and the activities of microsomal lauric acid hydroxylase, DMBA hydroxylase and progesterone 6 beta hydroxylase were several times lower in mullet liver than in rainbow trout liver; however, progesterone 16 alpha-hydroxylase and progesterone 20 alpha-hydroxylase activities were 4-fold and 6-fold higher, respectively, in mullet than in trout liver. PMID- 7881810 TI - Changes in the levels of different ions in the eggshell gland lumen following p,p'-DDE-induced eggshell thinning in ducks. AB - Eggshell thinning in ducks was induced by administration of p,p'-DDE in the diet (40 mg/kg food) for 45 days. This treatment resulted in a 19% reduction of the Eggshell Index (EI). Shells from calcifying eggs obtained at the time of slaughter showed a 36% reduction of EI. Prostaglandin synthesis by a homogenate of eggshell gland mucosa from p,p'-DDE-treated ducks was reduced by 24%. HCO3(-) stimulated ATPase activity by a homogenate of eggshell gland mucosa from p,p'-DDE treated ducks was not significantly changed. The calcium content of eggshell gland mucosa was increased to 127% in p,p'-DDE-treated ducks. p,p'-DDE-treated ducks showed profound changes in the shell gland luminal content of several ions. Calcium (-43%), sodium (-15%), potassium (-15%), bicarbonate (-33%) and chloride (-29%) were all significantly reduced in p,p'-DDE-treated ducks. The content of phosphate was unchanged. These findings are discussed in relation to a proposed mechanism for p,p'-DDE-induced eggshell thinning that involves inhibition of prostaglandin synthesis in eggshell gland mucosa. PMID- 7881811 TI - Toxicity of neomycin on enzyme activities of kidney and duodenal mucosa in vivo: organ specificity and species difference between rats and mice. AB - Inhibitory effects of neomycin administration (10-80 mg/kg body weight/day, s.c. for 7 days) on several enzyme activities of kidney and duodenal mucosa were compared between male rats and mice. In Wistar rat kidney, tubular brush border Mg(2+)-dependent, HCO3(-)-stimulated ATPase activity was inhibited by neomycin in a dose-dependent manner, while microsomal Mg(2+)-Na(+)-K(+)-ATPase activity and cytosol carbonic anhydrase (CA) activity were inhibited only by larger doses. In rat duodenal mucosa, Mg(2+)-HCO3(-)-ATPase and CA activities were also inhibited only by larger doses. Serum urea nitrogen (UN) concentration and urinary N-acetyl beta-D-glucosaminidase (NAG) activity were increased in a dose-dependent manner. In ddY and C57black mice, however, all enzyme activities in kidney and duodenal mucosa were almost unaffected by any dose of neomycin and showed no changes in serum UN concentration and urinary NAG activity except for ddY mice in which NAG activity was only increased by the largest dose of neomycin. In light microscopic analysis, 80 mg neomycin/kg produced necrosis in the greater part of rat proximal tubuli with no changes in duodenal brush border. On the other hand, no histological changes were produced in the renal cortex or duodenal mucosa of mice by any dosage. In conclusion, there are organ-specific and species differences in the effects of neomycin between rats and mice. PMID- 7881812 TI - Seasonal variations of pulsatile luteinizing hormone release in the mink (Mustela vison). AB - The pulsatile secretion of the hypophyseal luteinizing hormone (LH) is induced by the pulsatile secretion of the hypothalamic neurons secreting gonadotrophin releasing hormone (GnRH). Seasonal variations in the pulsatility of LH were studied in the adult male mink (Mustela vison), reared under natural environmental conditions. Twenty-one animals were studied according to five critical phases in the breeding season: (1) the terminal phase of sexual quiescence, which precedes renewal of gonadal activity (October-November); (2) renewal of gonadal activity (December); (3) maximum gonadal activity at the height of the breeding season (February); (4) reduction of testicular activity (April); and (5) the initial phase of testicular quiescence (June). Levels of gonadal growth and activity were used to define each phase. A second animal group was studied after being reared for 2 months in an experimental gonado-inhibitory photoperiod, which, necessarily for the mink, was of the "long-day" type: 20L:4D regimen in the present study. Results, obtained with fully conscious animals, provide evidence for the pulsatile secretion of gonadotrophic hormone in this species. In spite of inter-individual differences in pulse patterns, particularly in phases 1 and 2, the pulsatile character of LH secretion is seen to vary markedly as a function of gonadal activity. The variations reflect an increase of hypophyseal activity as early as the preparative phase to the breeding season, and a decrease of activity during the testicular regression phase, which is followed by the onset of gonadotrophic quiescence in June. The main parameter affected statistically by these seasonal fluctuations is pulse frequency; variations in pulse frequency correlated with variations in mean plasma concentrations of LH. In the experimental gonado-inhibitory photoperiod, which led to a severe reduction in gonadal activity, all hormonal pulsatility parameters were statistically reduced; this confirms the importance of photoperiodic control of reproduction in Mustela vison. Several possible mechanisms are proposed for photoperiodic control. PMID- 7881813 TI - Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates exocrine pancreas in conscious preruminating calves. AB - The effects of new hypothalamic peptides, PACAP-27 and PACAP-38, and secretin and VIP on the interdigestive pancreatic secretion and duodenal myoelectric activity during the asecretory phase of the pancreatic interdigestive cycle, compared with the milk ingestion phase, were examined in five calves. Peptides were infused for 5 min into the external jugular vein (0, 3, 10, 30 and 100 pmol/kg body wt during the asecretory phase of the pancreatic interdigestive cycle, and the pancreatic secretory response was compared with that obtained during milk ingestion. Intravenous infusion of PACAP-27 caused dose-related stimulation of pancreatic juice flow and bicarbonate and protein output; this effect was identical to infusion of secretin. The effect of PACAP-38 was less pronounced, and that of VIP was the weakest. Pancreatic juice volume and bicarbonate responses during milk ingestion were similar to responses obtained with the highest doses of hypothalamic peptides and secretin, whereas postprandial protein secretion was much greater than the secretion stimulated with peptides. It was concluded that PACAP from the VIP/secretin family may stimulate pancreatic exocrine secretion in conscious calves and a part of the pancreatic response to food intake can be mediated by PACAP. PMID- 7881814 TI - Transfer of fat-soluble vitamins and PCBs from mother to pups in grey seals (Halichoerus grypus). AB - Lactation in seals is characterized by a rapid and enormous lipid transfer from mother to pups within a milk rich in lipids. Since grey seals do not feed during lactation, all milk constituents are solely derived from body stores. Monitoring levels of fat-soluble vitamins as well as PCBs in blubber and milk may give an insight into the mechanisms involved in their mobilization from blubber, transfer into milk and deposition in the blubber of pups. During lactation, total lipids in milk increased from 261 to 601 g/l. While the level of PCBs in milk per g lipid remained constant throughout lactation, vitamin E, as well as vitamin A and cholesterol, showed a marked decrease during lactation when expressed as quantity per unit lipid. An incomplete transfer of all components from maternal blubber to milk was observed, except for vitamin E. The milk of pregnant females had vitamin E levels per unit which were three times higher than that in blubber, indicating a mobilization of vitamin E from the liver. During the later stages of lactation, there were no differences between the levels of vitamins A and E per unit lipid in the milk and the blubber of suckling pups. The close correlation of PCBs with total milk lipids and the drastic decrease in all other monitored fat-soluble components in seal milk with the progress of lactation point to different mechanisms of mobilization and transport for triglycerides and PCBs compared to fat-soluble vitamins and cholesterol. PMID- 7881815 TI - Trypanosoma cruzi: trypanocidal effect of 2(3)-tert-butyl-4-hydroxyanisole (BHA) on several strains of epimastigote and trypomastigote forms. AB - BHA (2(3)-tert-butyl-4-hydroxyanisole) produced inhibition of both culture growth and oxygen consumption, NAD(P) reduction and cytochrome b oxidation, on intact epimastigotes of Trypanosoma cruzi. BHA inhibited respiration and reduced NAD(P) in intact T. cruzi trypomastigotes. Oxidative phosphorylation of in situ mitochondria of epimastigotes was inhibited by BHA and this effect was liberated by the addition of ascorbate+TMPD. The incorporation of rhodamine-123 to mitochondria of living epimastigotes was diminished by BHA. These results suggest that the basis of the trypanocidal effects of BHA could be due to the blockage of the mitochondrial electron transport chain on the segment previous to cytochrome c. We postulate that the mechanism of action of BHA could be by mimicking coenzyme-Q (ubiquinone). PMID- 7881816 TI - Can hemolytic streptococci be considered "forefathers" of modern phagocytes? Both cell types freely migrate in tissues and destroy host cells by a "synergistic cross-talk" among their secreted agonists. PMID- 7881817 TI - Studies on responses to potassium, noradrenaline, serotonin, histamine and prostaglandin F2 alpha, of isolated pudendal arteries from non-lactating goats. AB - The effects of potassium (K+), noradrenaline (NA), serotonin (5-HR), histamine (Hi) and prostaglandin F2 alpha (PGF2 alpha) were studied on isolated pudendal arteries from non-lactating goats. K+, NA, 5-HT, Hi and PGF2 alpha had concentration-dependent contractile effects on the arteries. The developed tensions were, in order of potencies, 5-HT > NA > PGF2 alpha > Hi > K+. NA induced a significantly higher maximal contractile force than K+, 5-HT, PGF2 alpha and Hi. Pretreatment with cocaine was without significant effect on the contractile response to NA. The contractile response to Hi was totally eliminated by mepyramine. Ca2+ had a concentration-dependent contractile effect on arteries depolarized by 125 mM K+. The results indicate that NA, 5-HT and PGF2 alpha may play essential roles in the regulation of goat mammary blood flow. The response to K+ is highly dependent on extracellular Ca2+. The contractile response to histamine may be mediated via H1-receptors. The in vitro method used is well suited to study the vascular reactivity in different regions of the mammary vascular bed. PMID- 7881818 TI - Caffeine and coffee: effects on health and cardiovascular disease. AB - Caffeine is a methylxanthine whose primary biological effect is the competitive antagonism of the adenosine receptor. Its presence in coffee, tea, soda beverages, chocolate and many prescription and over-the-counter drugs makes it a commonly consumed stimulant. Coffee and/or caffeine consumption has been linked to many human diseases in epidemiologic studies. Causal relationships have been difficult to substantiate. Initial investigations, showing an association between coffee and coronary heart disease, suffer from confounding variables and have been difficult to replicate. Recent studies, showing a significant effect over long follow-up periods and with high coffee intake, have again raised the question of a role for coffee and/or caffeine consumption in the pathogenesis of atherosclerotic heart disease. Contrary to common belief, the published literature provides little evidence that coffee and/or caffeine in typical dosages increases the risk of infarction, sudden death or arrhythmia. PMID- 7881819 TI - Insulin-like growth factor-I messenger RNA content in the oviduct of Japanese quail (Coturnix coturnix japonica): changes during growth and development or after estrogen administration. AB - Complementary DNA (cDNA) of insulin-like growth factor-I (IGF-I) of Japanese quail was cloned. The nucleotide sequence analysis of the cDNA showed that only seven bases differed from those of chicken IGF-I cDNA in the 440 bases of the cloned region. This difference in nucleotide sequence did not cause changes in the amino acid sequence. Using this cloned cDNA, the changes in IGF-I mRNA content in the tissues of female quail during growth and development were investigated. In the oviduct, IGF-I mRNA was high about 5 weeks after hatching, concomitant with the rapid increase in total DNA content in this tissue (and the increases in total RNA content and RNA/DNA ratio). It decreased after 6 weeks, in accordance with the appearance of ovalbumin mRNA. When immature quails (6-day old) were injected with diethylstilbestrol (DES), induction of IGF-I mRNA was observed after 24 hr. A few days later, there was a strong induction of ovalbumin mRNA. These two inductions were dependent on the dose of DES. The sequential inductions of these two mRNAs were also noted when DES was re-administered to the immature quail to which it had been first administered and from which then withdrawn. The present results showed that IGF-I gene is expressed extensively during development of the oviduct, probably in accordance with the activity of DNA replication, because the highest IGF-I mRNA content was observed when the total DNA content of the tissues increased extensively. The results suggest that IGF-I in the oviduct of Japanese quail works in an autocrinal or paracrinal mode during the development of this tissue. PMID- 7881820 TI - A comparative study of effect of oral chronic cyanide administration on some rabbit tissue ATPases. AB - The effect of oral KCN administration on Na(+)-K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase activities was studied in some rabbit tissues. Generally, the order of activity of the enzymes was kidney > liver > ileum > colon. There were significant decreases (P < 0.05) in the activities of all the ATPases in the tissues of KCN-treated rabbits relative to controls. The decreases in Na(+)-K(+) ATPase and Ca(2+)-ATPase activities were most pronounced in liver and kidney. The decreases in ATPases suggest impairment of membrane function as a result of the toxic effect of cyanide. PMID- 7881821 TI - The large subunit of the pig heart mitochondrial membrane-bound beta-oxidation complex is a long-chain enoyl-CoA hydratase: 3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme. AB - The subunit locations of the component enzymes of the pig heart trifunctional mitochondrial beta-oxidation complex are suggested by analyzing the primary structure of the large subunit of this membrane-bound multienzyme complex [Yang S.-Y. et al. (1994) Biochem. biophys. Res. Commun. 198, 431-437] with those of the subunits of the E. coli fatty acid oxidation complex and the corresponding mitochondrial matrix beta-oxidation enzymes. Long-chain enoyl-CoA hydratase and long-chain 3-hydroxyacyl-CoA dehydrogenase are located in the amino-terminal and the central regions of the 79 kDa polypeptide, respectively, whereas the long chain 3-ketoacyl-CoA thiolase is associated with the 46 kDa subunit of this complex. The pig heart mitochondrial bifunctional beta-oxidation enzyme is more homologous to the large subunit of the prokaryotic fatty acid oxidation complex than to the peroxisomal trifunctional beta-oxidation enzyme. The evolutionary trees of 3-hydroxyacyl-CoA dehydrogenases and enoyl-CoA hydratases suggest that the mitochondrial inner membrane-bound bifunctional beta-oxidation enzyme and the corresponding matrix monofunctional beta-oxidation enzymes are more remotely related to each other than to their corresponding prokaryotic enzymes, and that the genes of E. coli multifunctional fatty acid oxidation protein and pig heart mitochondrial bifunctional beta-oxidation enzyme diverged after the appearance of eukaryotic cells. PMID- 7881822 TI - Glutathione S-transferases from the gastrointestinal nematode Heligmosomoides polygyrus and mammalian liver compared. AB - Glutathione S-transferases have been partially characterised from the gastrointestinal nematode Heligmosomoides polygyrus. Two major subunit families were purified (24 and 23 kDa) with N-terminal homology to the mammalian Alpha family. Four dimeric forms of GST were purified from the nematode by glutathione affinity chromatography, two major enzymes (pI 8.1, 5.0) and two minor forms (pI 5.8, 5.3). The purified GST pool could neutralize model and lipid peroxides via peroxidase activity but not peroxidation derived reactive carbonyls via glutathione transferase activity. Antisera raised to the pooled nematode GSTs appeared to recognize other Strongylida GSTs more strongly on Western blotting compared to mammalian GSTs. PMID- 7881823 TI - Phylogenetic conservation of ganglioside GD3 expression during early vertebrate ontogeny. AB - Gangliosides were investigated in adult brains and in 5-vesicle stage embryos of representatives belonging to the four vertebrate classes: Chondrichthyes, Amphibia, Aves and Mammalia. Considerable variability in brain ganglioside composition and concentration was observed among the adult vertebrates. The ganglioside patterns of the developmentally matched vertebrate embryos were similar in that each comprised GD3 as the predominant ganglioside. The phylogenetic conservation of abundant GD3 expression during early vertebrate ontogeny is interpreted as biochemical evidence consistent with von Baer's theory of increasing differentiation and suggests that GD3 is of critical importance for normal vertebrate development. PMID- 7881824 TI - Physiochemical and immunological comparisons between angiotensin I-converting enzymes purified from different mammalian species. AB - Angiotensin I-converting enzyme (ACE) was purified from lungs of pig, rat, monkey and human for comparison of its physicochemical, enzymatic and immunological properties. The protocol involved three chromatographic steps after detergent extraction, i.e. DEAE-Spherodex ion exchange, lisinopril-Sepharose affinity and Superose 12 HPLC, plus Mono-Q HPLC for monkey ACE. Purified ACE's presented numerous homologies: in particular, closely similar specific activities, catalytic efficiencies, Km's, optimal pH and chloride activations; the molecular weights were about 170 kDa by SDS-PAGE and 320 kDa by gel-filtration on Superose 12; the isoelectric points were about 4.5-4.7. Specific polyclonal antibodies recognized the antigen (porcine ACE) as well as rat, monkey and human ACEs. In contrast, three monoclonal antibodies (F02.4.1, F01.1.3 and F03) produced against porcine ACE showed some differences: they only reacted with pig enzyme and only one (F0.2.4.1) was anticatalytic. Moreover, the cross-reactivity judged on ELISA with porcine ACE characterized different epitopes specific for the porcine enzyme. In particular, the binding of F02.4.1 was not diminished by previous treatment with saturating concentrations of synthetic competitive ACE inhibitors. Thus, the extrapolation to human of data obtained on animal models should be possible at least for pharmacological and medical trials. PMID- 7881825 TI - Purification, characterization and amino terminal sequence of the superoxide dismutase from Babesia hylomysci. AB - Babesia hylomysci was found to contain two superoxide dismutase (SOD) isoenzymes with isoelectric points (pI) of 4.9 and 5.2. The two isoenzymes (45 and 47 kDa) were composed of two subunits of 22 kDa. An unique amino terminal sequence was determined up to 34 residues from the pooled isoenzymes and was identified as a sequence of SOD. The comparison of this N-terminal sequence of B. hylomysci SOD with 29 known Fe- or Mn-SODs showed more homologies with Fe-SODs. PMID- 7881826 TI - Relationship between the induction of proteins in the HSP70 family and thermosensitivity in two species of Oryzias (Pisces). AB - A cultured fish cell line, CE, derived from Oryzias celebensis, which lives in a tropical zone, was more heat-resistant than the OL32, which were derived from the Japanese medaka, Oryzias latipes which lives in a temperate zone. Protein synthesis in OL32 cells was also more heat-sensitive than that in CE cells. The relative levels in proteins of the HSP70 family and the ability of cells to tolerate severe heat treatment after a conditioning heat treatment were examined. Twenty-four hours after conditioning heat treatment, both cell lines retained thermotolerance even though three proteins in the HSP70 family had returned to their control levels. PMID- 7881827 TI - Characterization of liver flavin-containing monooxygenase of the dogfish shark (Squalus acanthias) and partial purification of liver flavin-containing monooxygenase of the silky shark (Carcharhinus falciformis). AB - Flavin-containing monooxygenase (FMO) activity as N,N-dimethylaniline (DMA) N oxygenation was characterized in microsomes from the smooth dogfish shark (Squalus acathias). DMA N-oxygenase activity from the liver of the dogfish shark was linear with increasing protein content and over 60 min. The optimal temperature for catalysis was 25 degrees C with a 76 percent reduction in activity when incubated at 15 degrees C and 99 percent loss of activity at 45 degrees C. Optimal pH was approximately 9.6. The maximum velocity for DMA N oxygenase activity was calculated to be 1.3 nmol min-1 mg-1 with an apparent Michaelis constant of 44 microM. Methimazole oxidase activity was also observed in dogfish liver microsomes which was inhibited by trimethylamine (TMA). Inhibition of DMA N-oxygenase activity by TMA and thiobenzamide was competitive, while inhibition by methimazole was not competitive. Western blot analysis indicated a single liver protein from both Squalus and Carcharhinus of approximately 50 kDa that bound to antibodies raised against FMO 2. An attempt was made to purify FMO as methimazole oxidase from the liver of the silky shark. A single peak of about 10-fold purity was observed following passage through two chromatographic media (CM-Sepharose and HA-Agarose). However, no activity was recoverable after the FMO-containing fractions were applied to a 2'5' ADP Sepharose column. PMID- 7881828 TI - Lipid composition of liver peroxisomes isolated from untreated and clofibrate treated mice and rats. AB - Peroxisomes were isolated from liver tissue of control and clofibrate-treated adult male NMRI mice and Sprague-Dawley rats. Phospholipids, cholesterol, triglycerides and free fatty acids were measured in the peroxisomes. The fatty acid profiles of the phosphatidylethanolamine, the phosphatidylcholine, the triglyceride and the free fatty acid fractions were also analyzed. Phosphatidylethanolamine was the dominating phospholipid in peroxisomes from untreated animals. The fatty acid profiles of phosphatidylethanolamine, free fatty acids and triglycerides were similar for untreated mice and rats but differences between the species were observed in the pattern derived from phosphatidylcholine. Phosphatidylcholine was the most abundant phospholipid after clofibrate treatment. Clofibrate treatment caused an increase in the concentrations of phospholipids and unsaturated long-chain fatty acids and a decrease in the concentrations of triglycerides, free fatty acids, cholesterol and shorter saturated fatty acids. PMID- 7881829 TI - Glutamine and glucose metabolism in intraepithelial lymphocytes from pre- and post-weaning pigs. AB - The metabolism of glutamine (Gln) and glucose was studied in intraepithelial lymphocytes (IEL) from 21-, 29- and 56-day-old pigs. Pigs were weaned at 21 days of age. Cells were incubated at 37 degrees C in the presence of Krebs-Ringer bicarbonate buffer (pH 7.4) containing 1 mM [U-14C]glutamine plus 5 mM glucose, or 5 mM [U-14C]glucose plus 1 mM glutamine. Glucose was converted to lactate, pyruvate and CO2, which accounted for 81, 11 and 8% of measured glucose carbon, respectively. Glutamine was metabolized mainly to glutamate (92% of Gln C) and ammonia, and to a lesser extent, to aspartate (4% of Gln C) and CO2 (4% of Gln C). In the presence of both glucose and glutamine, glucose provided 2-3-fold more ATP to IELs than glutamine in 21-56-day-old pigs, on the basis of their measured end products. The rates of ammonia and glutamate production from glutamine in IELs from 29-day-old pigs were 112 and 90% greater than those in cells from 56 day-old pigs, respectively. The rates of glucose oxidation to CO2 in IELs from 29 day-old pigs were elevated 56 and 64% respectively, compared with 21- and 56-day old pigs. Elevated rates of substrate metabolism in IELs from 29-day-old post weaning pigs indicated a metabolic alteration of these cells possibly due to changes in diet and intestinal bacterial population. PMID- 7881830 TI - Antibacterial protection in Marthasterias glacialis eggs: characterization of lysozyme-like activity. AB - Eggs from Marthastherias glacialis exert antibacterial action on marine bacterial strains and show a lysozyme-like activity. This one depends on pH and ionic strength of sample and reacting medium. This hydrolase, purified by gel filtration and ion-exchange chromatography, could be responsible for the bacterial growth inhibitory activity observed. PMID- 7881831 TI - Bits and pieces in a puzzle--rheumatoid arthritis and pregnancy. PMID- 7881832 TI - Lamellar body secretion: ultrastructural analysis of an unexplored function of synoviocytes. AB - The intra- and extracellular distribution and relative density of lamellar bodies (LBs) were determined by electron microscopy in synovial biopsies from 20 non rheumatoid arthritis (RA) patients. LBs were found on the synovial surface, in intimal cells, throughout intimal matrix, in blood vessel walls, in endothelial cytoplasm and within vascular lumena. Lamellar profiles were observed in type B synoviocytes within rough endoplasmic reticulum (RER), in association with the Golgi apparatus, and embedded in electron dense matrix (projection cores) in multivesicular bodies. Exocytotic release of mature LBs into intimal matrix was observed. In type A synoviocytes the outer lamellae of LBs were frequently found in contiguity with the limiting membrane of lysosomes. An in vitro investigation of the ultrastructural features of LB formation in cultured type B synoviocytes (from 3 non-RA patients) gave results similar to those obtained in biopsies. These studies provide ultrastructural evidence of synoviocyte activity in secreting and degrading phospholipid lubricant in a sophisticated system whose function and pathological derangements are largely unknown. PMID- 7881833 TI - Increased IL-1 receptor antagonist (IL-1ra) production and decreased IL-1 beta/IL 1ra ratio in mononuclear cells from rheumatoid arthritis patients. AB - In order to investigate the possible role of IL-1 receptor antagonist (IL-1ra) in patients with rheumatoid arthritis (RA), this study was undertaken to measure the amounts of IL-1ra and interleukin-1 beta (IL-1 beta) protein produced by mononuclear cells (MNC) and to investigate the relationship between production of these cytokines and clinical parameters. The MNC were cultured for 24 h and the supernatants were measured for IL-1ra and IL-1 beta by ELISA kits. MNC from peripheral blood (PB) and synovial fluid of RA patients produced significantly higher amounts of IL-1ra than normal PBMNC (P < 0.01 and P < 0.05, respectively). When the IL-1 beta/IL-1ra ratio was calculated, IL-1 beta/IL-1ra ratios of RA PBMNC were significantly lower than those of normal PBMNC (P < 0.001). The IL-1 beta/IL-1ra ratio of RA PBMNC was significantly higher in active RA patients than in RA patients in remission (P < 0.02). The amounts of IL-1ra produced by stimulated RA PBMNC positively correlated with the joint score (P < 0.05), serum CRP levels (P < 0.05) and the amounts of IL-1 beta produced (P < 0.01). The amounts of IL-1ra produced by unstimulated RA PBMNC did not correlate with any of the clinical parameters studied. Gold sodium thiomalate (GST), but not auranofin, increased IL-1ra production in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881834 TI - The management of systemic sclerosis. PMID- 7881835 TI - Determination of various cytokines and type III procollagen aminopeptide levels in bronchoalveolar lavage fluid of the patients with pulmonary fibrosis: inverse correlation between type III procollagen aminopeptide and interferon-gamma in progressive patients. AB - We measured levels of cytokines and type III procollagen aminopeptides (procollagen III peptides) in bronchoalveolar lavage fluid obtained from 20 patients with stable pulmonary fibrosis (PF) and seven patients with progressive PF, and nine control subjects to determine the role of cytokines in the development of PF. Procollagen III peptide levels were markedly increased in progressive PF patients. Tumour necrosis factor-alpha, interleukin-6, transforming growth factor-beta and interferon-gamma (IFN-gamma) levels were elevated in both PF patients as compared with controls, with a tendency of higher levels in progressive patients, whereas interleukin-1 beta (IL-1 beta) level was decreased in both PF patients. When the correlation between procollagen III peptide and various cytokine levels was analysed the only significant correlation was inversely between procollagen III peptide and IFN-gamma in progressive PF patients. These results indicated that although multiple cytokines may be involved in the development of PF, the negative role of IFN-gamma in active collagen synthesis could be also important. PMID- 7881836 TI - Association of HLA-DR4, protease inhibitor phenotypes and keratoconjunctivitis sicca with pulmonary abnormalities in rheumatoid arthritis. AB - One-hundred rheumatoid arthritis (RA) patients were assessed for the association of HLA-DR4, protease inhibitor (Pi) phenotype and keratoconjunctivitis sicca (KCS) with a variety of clinical features, airflow obstruction and bronchial reactivity. Spirometry, lung volume and gas transfer factor measurements were performed to detect airflow obstruction. Bronchial reactivity to inhaled methacholine was assessed by measuring the provocative dose of methacholine causing a 20% fall in FEV1 from the baseline (PD20). Sixty-two patients were HLA DR4 positive, 87 had Pi MM and 13 MS phenotypes and 37 had positive Schirmer's tear tests. Patients with KCS had a significantly increased history of wheeze (11/37 vs 7/63, P = 0.03, relative risk (RR) 1.8 [95% CI 1.04, 3.1]), those with HLA-DR4 had a significantly decreased atopy on skin-prick testing [3/62 vs 7/38, were significantly higher in the Pi MS group compared to Pi MM group. There was no significant association of HLA-DR4, Pi phenotype and KCS with bronchial reactivity. We conclude that there is no overall significant association of HLA DR4, Pi phenotype and KCS with airflow obstruction and bronchial reactivity in RA. PMID- 7881838 TI - Acute sarcoid arthritis: occurrence, seasonal onset, clinical features and outcome. AB - In a 2-yr prospective follow-up study of patients presenting clinically with possible reactive arthritis (ReA), 17 (9%) of the patients turned out to have acute sarcoid arthritis (SA). The number of new cases of SA per year was 2.9/100,000 persons in the city of Oslo between 18 and 60 yr of age. The onset of SA clustered in the spring. All the SA patients presented with bilateral ankle joint involvement and bilateral hilar lymphadenopathy, and ten (59%) presented with the triad of erythema nodosum, arthritis and lung involvement. A prospective follow-up after 104 weeks showed complete remission of arthritis in all 17 cases of SA. The total duration of arthritis [median (range)] was 11 (2-107) weeks. Erythema nodosum was mild and transient in all cases. At week 104, the lung and hilar manifestations had resolved. We conclude that the outcome of SA appeared favourable. Bilateral ankle joint involvement, erythema nodosum and bilateral hilar lymphadenopathy found at the routine chest X-ray examination are important clues for the diagnosis of SA. PMID- 7881837 TI - Compound heterozygosity of HLA-DR4 and DR1 antigens in Asian Indians increases the risk of extra-articular features in rheumatoid arthritis. AB - The relationship of HLA-DR antigens in rheumatoid arthritis (RA) patients with the presence of rheumatoid factor (RF), extra-articular features, joint erosions, functional status and response to disease modifying anti-rheumatic drugs (DMARDs) was studied. Seventy-four patients with RA were serologically typed for class II antigens. Clinical features were recorded before starting DMARDs and during follow-up to assess response and side-effects. HLA-DR1 and DR4 antigens were present more frequently in patients with RA than in the general population. The presence of DR4 correlated with RF seropositivity (P < 0.001) while DR1 was associated with seronegativity (P < 0.02). Ten of the 11 patients with extra articular features had DR1 and/or DR4. Patients with both DR4 and DR1 had a significantly higher frequency of extra-articular features compared with those with only one of these (P < 0.01). HLA-DR4 and DR1 had no relation with the presence of subcutaneous nodules, erosive changes, deformities, response to drugs and side-effects of DMARDs. PMID- 7881840 TI - Proposed modification to Larsen's scoring methods for hand and wrist radiographs. PMID- 7881839 TI - Small joint synovitis in rheumatoid arthritis: should it be assessed separately? AB - In the assessment of disease activity in rheumatoid arthritis (RA) small joint synovitis is traditionally included only as a component of active, tender or swollen joint counts. By contrast, in the assessment of disease damage in RA, the X-ray score of hands and feet represents one of the most common parameters used and is regarded as a major indicator of outcome. Data presented in this study lead us to hypothesize that the small joints require separate assessment in any study of disease activity or outcome in RA: (i) there is clear evidence that small joint synovitis often occurs in the absence of an abnormal acute phase response (ESR or C-reactive protein) and (ii) measured synovitis is an individual (PIP) joint has been shown to be reliable and to be related to subsequent X-ray changes in the same joint. Our findings show that, in a study of a treatment of RA, it is quite possible for disease activity measures to appear controlled while inflammation continues in the small joints causing radiological damage. This radiological damage is reflected as an adverse outcome. Hence the paradox of improving disease activity but not outcome. We argue that small joint inflammation and damage should be recognized as one aspect of the RA disease process offering unique information and as such should be assessed independently. PMID- 7881841 TI - A letter from Australia. PMID- 7881842 TI - The pain threshold in juvenile chronic arthritis. AB - An algometer was used to study the pain threshold (PT) on pressure at the joint capsules of the wrists, elbows, knees, ankles and at paravertebral soft tissues in 57 patients with juvenile chronic arthritis (JCA) and 69 healthy controls, aged 6-17 yr. The PTs were correlated to visual analogue scales (VAS) and values of articular disease activity, to define their relation with pain perception and joint inflammation. The PTs in JCA patients were significantly lower than in their healthy peers, both in children with active inflammation as well as in children without detectable inflammation. The JCA group with active inflammation showed significant lower PTs than without detectable inflammation. Disease activity and VAS correlated significantly with PT (r = -0.5). There is an enhanced sensitivity to noxious stimuli in all measured body areas, suggesting a change in the pain processing system in JCA. The sensitivity endures in JCA patients without clinically active disease, probably due to prolonged central sensitization after periods of active disease. PMID- 7881843 TI - Idiopathic juvenile osteoporosis: experience of twenty-one patients. AB - The features and outcome of 21 children (12 boys, nine girls) with idopathic juvenile osteoporosis (IJO) followed for up to 23 yr are described. The mean age of onset was 7 yr (range 1-13 yr) with no sex difference; the main presenting symptoms were long bone fractures, pain in the back and difficulty in walking. Typically, radiographs demonstrated compression of the vertebrae and metaphyses of the long bones; bone histology sometimes showed an excess of osteocytes associated with woven bone; routine biochemistry was normal for age; and with three exceptions no abnormalities of extracted dermal collagen or collagen synthesized by fibroblasts were detected. Where circulating vitamin D metabolites were measured they were within the normal range; and hip and spine bone mineral density (measured by DXA) was strikingly low. Five patients are still growing and two are currently untraceable. Of the remaining 14 who are now adults, 11 have substantially or completely recovered and three are disabled. Since spontaneous recovery occurs it remains impossible to assess the many forms of treatment given. PMID- 7881844 TI - Differential diagnosis and management of hip pain in childhood. AB - Hip pain in children is always potentially serious. Different specialists see a different spectrum of hip diseases. Acute hip pain is usually referred to the surgeons, and the principal concern is to distinguish sepsis of the hip joint or pelvic bones from irritable hip: untreated sepsis can destroy the hip within days, but its presentation may be atypical or mild and investigations misleading. A reliable protocol for the management of acute hip pain in children is now available. Perthe's disease and slipped capital femoral epiphysis is usually evident on the initial radiograph. Hip disorders with a subacute or chronic presentation are usually referred to the paediatrician or rheumatologist. If examination shows restriction of hip movement or there are radiographic abnormalities, many will have a serious disorder requiring long-term management. The diagnosis is often apparent on the initial radiographs, although special imaging techniques may be needed. In a monoarticular presentation of juvenile arthritis, the hip radiograph will be normal but the diagnosis evident from other clinical features or blood investigations. Recognition of non-organic syndromes presenting with hip pain requires the exclusion of organic causes and an alertness to the incongruity of the physical signs. PMID- 7881845 TI - Corticosteroid osteoporosis. AB - Cortocosteroids have profound effects on bone, leading to accelerated osteoporosis and fracture. This review will attempt to summarize current knowledge about their effects in light of new information and important remaining questions, especially with respect to treatment of this common condition. PMID- 7881846 TI - High free and latent collagenase activity in psoriatic arthritis synovial fluid. PMID- 7881847 TI - Fatal vasculitis following treatment with co-trimoxozole. PMID- 7881848 TI - Suppression of proteinuria and prolongation of survival in MRL-lpr/lpr mice treated with sulphasalazine. PMID- 7881849 TI - High diagnostic value of antiperinuclear factor-IgG: prospective analysis of 1004 sera diluted 1:100 and more. PMID- 7881850 TI - Proinflammatory role of tissue kallikrein in modulating pain in inflamed joints. PMID- 7881851 TI - Hypocomplementaemia, C3 nephritic factor and type III mesangiocapillary glomerulonephritis progressing to systemic lupus erythematosus. PMID- 7881852 TI - [Role of carcinogenic polycyclic aromatic hydrocarbons in the etiology of lung cancer morbidity among the population a of a large industrial city]. AB - The article deals with results of studies covering the levels of carcinogenic aromatic hydrocarbons including benzpyrene (an indicator) in atmosphere of various districts within an industrial city. Concentrations of toxic substances, heavy elements, radioactive aerosols in the air were also analyzed. Lung cancer morbidity among the population was studied. By means of poll among the patients the scientists revealed the duration of residence in various districts within the city, occupational background, bad habits, which preceded lung cancer. Close correlation between lung cancer incidence and air pollution with benz(a)pyrene was seen. Threshold concentrations of the carcinogen were estimated. Role of smoking and air pollution in lung cancer morbidity were determined. PMID- 7881853 TI - [Diurnal rhythm of physiologic functions in workers exposed to noise]. AB - To reveal the mechanisms of adaptation to occupational factors, the authors screened the workers exposed to noise for changes of pulse rate, blood pressure, catecholamines content, auditory threshold within a day. The study showed that adaptation to unfavorable work conditions deteriorates within a day (from morning to night shifts). Reliability of catecholamines level was conditioned by the night fall of catecholamines level and its changes within a day. Compromised adaptation to chronic unfavorable occupational factors result in unstable catecholamines level. Functional state of hearing is mediated by vegetative state including catecholamines content. PMID- 7881854 TI - [Several points concerning hygienic standardization and evaluation of industrial noise and vibration]. AB - The author suggests a universal parameter for hygienic characterization of mechanical oscillation in industry--an energy level of oscillation. That enabled to unify criteria of evaluation, to considerably simplify vibration and acoustic calculations. The article gives formulae to evaluate doses of noise and vibration, including those regularly interrupted. Acceptability range limits for use of calculated levels of noise and vibration are set. PMID- 7881855 TI - [Characteristics of changes in intellectual activities caused by hypoglycemia in operators]. AB - The article deals with data obtained from studies of operators' activity changes caused by artificial hypoglycemia. Hypoglycemia of operator appeared to markedly alter the quality, psychologic and physiologic intensity, subjective appraisal of intellectual activities. Overall, hypoglycemia leads to intensified signs of fatigue during mental work. In this case hypoglycemia affects the processes of verbal and logic decision more than perceptive and identification activities. Besides that, hypoglycemia appeared to worsen the processes of operators' cooperation in decision. The studies showed that in order to support the necessary level of capacity to work the mechanisms of adaptation and mobilization of psychologic and physiologic resources become activated in hypoglycemia. PMID- 7881856 TI - [Printing industry as a source of carcinogenic danger to the workers (review of the literature)]. PMID- 7881857 TI - [Occupational medicine as real and nearest future]. PMID- 7881858 TI - [Antithesis to principles underlying formation of occupational medicine services]. AB - Basing a personal point of view, the author doubts that creation of "Industrial medicine" service at the enterprises is expedient for now. The author is concerned that the service could be transformed into closed official establishment having no power of state service for sanitary and epidemiologic supervision. Organizational and economic difficulties connected with construction of such service are also stressed. This point of view underestimates considerable experience accumulated by the national medical practice and the difficulties associated with professional training of the specialists in industrial hygiene. PMID- 7881859 TI - [Use of insoles made of antimicrobial materials as prophylactic means in foot mycoses]. AB - Stationary dermatologic examination covered 32 sufferers from epidermophytosis of soles, who used 3 types of antimicrobial insoles chosen through laboratory investigations. Clinical trials proved that antimicrobial insoles, if applied during 2 weeks, result in considerably decreased occurrence of causal fungus in the patients' surface skin scarring. The results proved fungicidal and bactericidal activity of insoles including furagin, nitrofurilacroleine, polyhexamethylene guanidine, so such insoles could be recommended as prophylactic measure for mycoses of soles. PMID- 7881860 TI - [Hygienic regulation of yttrium, terbium, ytterbium and lutetium fluorides in the air of the workplace]. AB - The study (experiments on animals and on culture of rats' peritoneal macrophages) covered fluorides of rare-earth metals (REM) assigned to yttrium group--yttrium, terbium, ytterbium, lutetium. Fluorides of REM have low toxicity and cumulativity, induce no local irritation of skin and eyes. Fluorides of yttrium, terbium and lutetium, if administered into stomach, result in specific intoxication (fluorosis). Fluoride of ytterbium did not cause such intoxication. According to short-term tests of cytotoxicity, the foreseeable fibrogenic danger for ytterbium fluoride is moderate, for fluorides of yttrium, terbium and lutetium is mild. The authors recommend to control the level of yttrium, terbium and lutetium fluorides in the air of workplace through the MACs for the fluorides at 2.5 mg/cu m (maximal single concentration) and 0.5 mg/cu m (average shift concentration), the level of ytterbium fluoride as moderate fibrogenic dust at 6 mg/cu m. PMID- 7881861 TI - [Lipid metabolism in humans exposed to environmental heat]. PMID- 7881862 TI - [Preliminaries to a study of epidemiology of occupational cancer among workers of shoe factories]. AB - Data presented in literature proves frequent malignancies of various localizations in workers engaged into footwear production, which could result from exposure to leather, rubber dust and some chemicals (polyvinylchloride, chloroprene and others). Hygienic studies of air at footwear production demonstrate that the workers at their workplaces are exposed to such occupational hazards as dust, chemicals. Epidemiologic research to reveal possible correlation between work conditions and the workers' health are expedient. PMID- 7881863 TI - [Diagnosis of borderline neuropsychiatric disorders in persons exposed to occupational physical factors]. AB - The article deals with analysis of methodic approaches to diagnose of boundary neuropsychopathies (BN), covers the results of screening among industrial workers exposed to such physical occupational factors as sensory deprivation, noise and vibration, electromagnetic fields in cm and dm ranges. The screening was conducted by means of the authors' method for early diagnosis. The obtained results proved that incidence of BN and their structure depend to a large extent on special characteristics of occupational factors. Multivariate statistics helped to define most probably reactions of psychic sphere to the studied occupational factors. PMID- 7881864 TI - Expression of mRNA's of cytokines and growth factors in experimental glomerulonephritis. AB - A variety of cytokines and growth factors have been recently shown to modulate the growth of mesangial cells and the synthesis of the mesangial matrix. We examined chronological change of mRNA expression of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor beta 1 (TGF-beta 1), and the platelet-derived growth factor (PDGF)-B chain in glomeruli of nephrotoxic serum nephritis using reverse transcription and the polymerase chain reaction (RT-PCR) method. Expression of TNF-alpha mRNA increased immediately after induction of nephrotoxic serum nephritis. Levels of IL-1 beta and PDGF-B chain mRNAs increased at 24 hr and remained elevated for 4 weeks. TGF beta 1 mRNA expression increased significantly at 24 hr, peaking at 2 weeks. The chronological changes of these cytokines and growth factors were associated with two phases of inflammation in this model. Among them, expression of PDGF-B chain mRNA preceded mesangial proliferation and expression of TGF-beta 1 preceded accumulation of mesangial matrix, indicating that these two growth factors contributed to these histological alterations. PMID- 7881865 TI - Regional changes in alpha-tubulin and beta-actin mRNA accumulations after transient ischemia in spontaneously hypertensive rat brains. AB - Regional changes in the mRNA accumulations for cytoskeletal proteins alpha tubulin and beta-actin were examined by in situ hybridization and Northern blot analysis in spontaneously hypertensive rat brains at chronic stages after 3 hours of transient ischemia. alpha-Tubulin mRNA accumulations showed no significant change at 2 weeks after transient ischemia except for a significant decrease in the frontal cortex (9.7%, p < 0.01) coinciding with ischemia induced histological changes. beta-Actin mRNA level was significantly increased in the parietal cortex (8.5%), septum (10.0%), amygdala (11.0%), CA4 area (5.8%) and the dentate gyrus (7.5%) of the hippocampus at 2 weeks after recirculation compared with a sham operated control group (p < 0.01). The ischemic areas of hippocampal and frontocortical lesions receive afferent neurons from those regions where beta actin mRNA was increased, suggesting that ischemia-induced increases in beta actin mRNA may reflect actin synthesis in these neurons to compensate for lost synaptic connections. Two cytoskeletal mRNA concentrations reacted differently to cerebral ischemia, and did not parallel histological signs of ischemia either temporally or spatially. PMID- 7881866 TI - Protein kinase C modulation of rhodanese-catalyzed conversion of cyanide to thiocyanate. AB - Detoxification of cyanide is catalyzed by a sulfurtransferase, rhodanese, a phosphoprotein regulated by unknown protein kinases. In this study, we determined if a Ca2+/phospholipid-modulated phosphotransferase, protein kinase C (PKC) could modify rhodanese activity. Thiocyanate (SCN-) production as an estimate of rhodanese activity in vitro was measured in the presence or absence of exogenously added purified PKC, or 12-O-tetradecanoylphorbol acetate (TPA), a pharmacologic activator of the endogenous PKC. HI-6 (1-(2 (hydroximino)methyl))pyridinium-2-(4-(aminocarbonyl) pyridinium dimethylether) is an oxime that may dephosphorylate phosphoproteins due to the proposed phosphatase like activity of the oximes. We examined HI-6's effect on rhodanese-catalyzed SCN production. Bovine kidney rhodanese (0.40 mg/ml protein) was reacted with 4 mM KCN and SCN- production determined spectrophotometrically following the method of Westley (1981). Preincubating rhodanese with 20 or 100 ng of purified PKC (alpha, beta, gamma isozymes) for 5 min before initiating the reaction with 4 mM KCN as the substrate increased SCN- production by 17 or 40%, respectively, over the control (P < 0.05). Rhodanese formation of SCN- decreased when the preincubation was conducted with 1 nM or 100 nM of TPA. With HI-6 at 1 or 10 microM used in place of PKC, or TPA, rhodanese activity was increased by 6 or 14% (P < 0.05), respectively, compared to control. Under the conditions examined, exogenous PKC acting as a possible phosphate acceptor, and HI-6, a potential dephosphorylating compound, increased rhodanese activity. These data are consistent with the observation that rhodanese can exist as a phosphorylated enzyme which is not active and a dephosphorylated form which is active. It is suggested that addition of purified, exogenous PKC may accept phosphate from phosphorylated rhodanese or HI-6 may dephosphorylate rhodanese, both of which stimulate the conversion of cyanide anion to the less toxic SCN-. These observations support the possibility that rhodanese may be regulated by protein phosphorylation and treatments that alter the phosphorylation state of rhodanese may affect cyanide detoxification via SCN- formation. PMID- 7881868 TI - Reduced drug resistance in a multidrug resistant cell line by 5,8,11,14 eicosatetraynoic acid. AB - We examined whether the arachidonic acid competitive antagonist, ETYA (5,8,11,14 eicosatetraynoic acid), modulated drug sensitivity in a cell line that over expresses the multiple drug resistance protein, MDR1. ETYA was nontoxic to drug sensitive parental KB3-1 cells or drug-resistant MDR KB8-5-11 cells, with an IC50 of 190 microM for both lines. ETYA (20 microM) increased rhodamine 123 accumulation in KB8-5-11 MDR cells but not in KB3-1 sensitive cells. Arachidonic acid at 20 microM did not alter rhodamine accumulation in either cell line. Increasing the concentration of ETYA from 40 to 160 microM or incubation beyond 30 min did not increase KB8-5-11 dye retention. Forty microM or more ETYA increased KB3-11 dye retention. In a 6 day proliferation assay of KB8-5-11 cells, a nontoxic (40 microM) concentration of ETYA reduced the IC50 for doxorubicin 4 fold, the IC50 for colchicine 2-fold, but had no effect on the IC50 for vinblastine. ETYA at 40 microM did not alter the IC50 for any drug tested with KB3-1 cells. Therefore: (a) ETYA (20 or 40 microM) modulated resistance of KB8-5 11 cells to several drugs to a limited extent, without potentiating toxicity in the parental line, while arachidonic acid did not. (b) Since cationic rhodamine 123 is concentrated in mitochondria, the extent is dependent upon the transmembrane potential, and increased dye retention due to ETYA may in part be related to altered ETYA-induced cell membrane potential. PMID- 7881867 TI - Differences in metabolism between 26,26,26,27,27,27-hexafluoro-1 alpha, 25 dihydroxyvitamin D3 and 1 alpha, 25-dihydroxyvitamin D3 in cultured neonatal mouse calvaria. AB - We investigated the metabolism of 26,26,26,27,27,27-hexafluoro-1 alpha,25 dihydroxyvitamin D3 (26,27-F6-1,25(OH)2D3, ST-630) and 1 alpha,25 dihydroxyvitamin (1,25(OH)2D3) in cultured neonatal mouse calvaria to elucidate why ST-630 is more potent than 1,25(OH)2D3 in stimulating bone resorption in organ culture. The metabolites were extracted with ethyl acetate or chloroform/methanol (1:1) from cultured calvaria or medium incubated with [3H]-ST 630 or [3H]-1,25(OH)2D3 for various periods, and separated by high performance liquid chromatography. [3H]-ST-630 in cultured calvaria was converted to [3H] 26,26,26,27,27,27-hexafluoro-1 alpha,23(S),25-trihydroxyvitamin D3(26,27-F6 1,23,25(OH)3D3,ST-232), which stimulated bone resorption equipotently as 1,25(OH)2D3. The amount of [3H]-ST-232 produced in the bone increased with passage of the culture period. In contrast, the amount of [3H]-ST-630 in the bones decreased in the 2 day cultures. In the medium, [3H]-ST-630 was hardly detectable for 2 days. This suggests that ST-630 is metabolized to ST-232 which is retained in the bones. On the other hand, some [3H]-1,25(OH)2D3 was metabolized to inactive forms detectable in the medium. Therefore, the high potency of ST-630 in stimulating bone resorption in organ culture may be associated with a difference between ST-630 and 1,25(OH)2D3 in the mode of metabolism in the cultured bones. PMID- 7881869 TI - Interaction of renal excretion between nilvadipine metabolites, M3 and M7 in rats: characterization of sex-dependent and sex-independent active secretion in the kidney. AB - The interaction of renal clearance between nilvadipine metabolites, M3 and M7, in male and female rats including protein binding and renal excretion was investigated to clarify the mechanisms involved. In male rats, active renal secretion of M7 (the 5-carboxylic acid pyridine derivative) was reduced in inverse proportion to the molar ratio of the plasma concentration M3/M7 after an i.v. dose of M3 (the 3-carboxylic acid pyridine derivative), and the dosed M3 was excreted only by glomerular filtration. In female rats, the active renal secretion of M7 was unaffected after an i.v. dose of M3, and the dosed M3 was excreted by active secretion. These results indicate an interference of the active secretion of M7 in male rats by M3 on competitive interaction at the renal tubular secretion, even though M3 was excreted only via a filtration process. Female rats may have two distinct and separate active renal secretion mechanisms for M7 and M3, even though these carboxylic acid compounds were eliminated by active transport in the kidney. PMID- 7881870 TI - Exocytosis in neutrophils induced by thapsigargin and other inhibitors of calcium ATP-ase. AB - Inhibitors of the Ca(2+)-ATPase of intracellular calcium stores, such as thapsigargin, cyclopiazonic acid and 2,5-di-(t-butyl)-1,4-benzohydro-quinone, causes exocytosis in rabbit peritoneal neutrophils. In the absence of extracellular Ca2+ no exocytosis takes place. Fluoride, a non-specific inhibitor of Ca(2+)-ATPase, also causes exocytosis. It is known that all agents tested cause both a release of calcium from intracellular stores as well as an influx of extracellular calcium. The results indicate that induction of exocytosis is not due to a release of calcium from intracellular stores, but to the influx of extracellular calcium. Thapsigargin-induced exocytosis is not inhibited by L-type channel antagonists like verapamil, but is strongly inhibited by lanthanum ions, suggesting that the calcium required for induction of exocytosis is not entering via L-type channels, but via La(3+)-sensitive calcium channels. PMID- 7881871 TI - Time course of lipid peroxidation in puromycin aminonucleoside-induced nephropathy. AB - Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy. PMID- 7881872 TI - Mechanisms of gastric antisecretory action of pentylenetetrazol in rats. AB - The present study investigated the mechanisms of gastric antisecretory action of pentylenetetrazol (PTZ) in pylorus-ligated rats. Pretreatment with indomethacin, phentolamine, propranolol, 6-hydroxydopamine, flunarizine and nifedipine, which were reported to antagonize seizures induced by PTZ, did not influence the gastric antisecretory action of PTZ. In contrast, pentobarbital and phenobarbital reverse the action of PTZ. These results suggest that prostaglandins production, adrenoceptors and calcium entry are not involved in the gastric antisecretory action of PTZ, and that the GABAA receptor complex plays an important role in the action induced by PTZ. PMID- 7881873 TI - Effects of chelating agents on tissue distribution and excretion of nickel in mice. AB - N-Benzyl-D-glucaminedithiocarbamate (BGD), diethyldithiocarbamate (DDTC), di hydroxyethyldithiocarbamate (DHED), trans-1,2-cyclohexanediamine N,N,N',N'-tetra acetic acid (CDTA), and 2,3-dimercaptosuccinic acid (DMSA) were studied for their relative efficacies in the distribution and excretion of nickel in mice exposed to nickel. Mice were injected intraperitoneally with NiCl2 (5mgNi/kg) and 30 min or 24 hr later, they were injected intraperitoneally with chelating agents (400 mumol/kg). At 30 min after treatment with nickel, these chelating agents all significantly enhanced the fecal excretion of nickel, and DMSA significantly increased the urinary excretion of the metal. At 24 hr after nickel treatment, BGD, DDTC, and DHED significantly increased the fecal excretion of nickel and BGD was the most effective on the fecal excretion of nickel. CDTA and DMSA significantly enhanced the urinary excretion of the metal. At 30 min after nickel treatment, chelating agents other than CDTA effectively depressed nickel concentration in the kidney, lung, and testes. BGD, CDTA, and DMSA significantly reduced the nickel concentration in the liver. However, DDTC and DHED caused the redistribution of nickel to the brain. At 24 hr after nickel treatment, these chelating agents were effective in mobilizing nickel from the kidney, and chelating agents other than DHED were effective in mobilizing nickel from the liver, lung, and testes. These results indicate that the injection of BGD or DMSA at both 30 min and 24 hr after treatment with nickel can remove nickel from the body without redistribution of nickel to other tissues, such as brain, more effectively than DDTC, DHED, and CDTA. Furthermore, the pattern of excretion of nickel after treatment with the chelating agents was related to the partition coefficients of the nickel-chelating agent complexes. PMID- 7881874 TI - Archives of clinical skiagraphy. 1896. PMID- 7881875 TI - Mackenzie Davidson Memorial Lecture 1994: imaging of treated cancer. PMID- 7881876 TI - Variations in the radiological management of intussusception: results of a postal survey. AB - A survey of the radiological reduction of intussusception in a selection of British hospitals was performed using a questionnaire. Replies were received from radiologists working in 51 district general hospitals and 25 teaching hospitals or specialist paediatric institutions. Most district general hospitals still use barium as the sole method of reduction of intussusception. Most teaching hospitals and specialist paediatric units have changed to a pneumatic method. The contra-indications, details of patient preparation and technical details of each method varied considerably. PMID- 7881877 TI - Radiation dose to the lens from computed tomography scanning in a neuroradiology department. AB - The radiation dose to the lens was measured by thermoluminescent dosimetry on 194 patients undergoing routine head and neck computed tomography scanning in a neuroradiology department. The results are lower than previously reported: brain scans, mean value 5.1 mGy; orbital scans, mean value 18.5 mGy; and direct coronal pituitary scans, mean value 1.9 mGy. These lower values in axial brain scans are due to use of the supraorbital meatal baseline for radiographic positioning. PMID- 7881878 TI - Angiographic contrast media relax isolated rabbit aorta through an endothelium independent mechanism that may not depend on the presence of the iodine atom. AB - Systemically administered iodinated angiographic contrast media evoke vasodilatation through mechanisms that are at present poorly understood. In the current investigation we have evaluated the role of the vascular endothelium in responses to an iso-osmolar formation of the non-ionic dimer iodixanol and a hyperosmolar formulation of the non-ionic monomer iopromide. Isolated rabbit aortic ring preparations with endothelium intact or removed by gentle abrasion were mounted in organ baths containing oxygenated Holman's solution, and cumulative concentration-response curves for relaxation to the contrast media were constructed after pre-constriction by phenylephrine (300 nM) in the presence of indomethacin to inhibit prostaglandin synthesis. Endothelial denudation did not influence the ability of either iodixanol or iopromide to relax the aortic ring preparations. Iopromide was significantly more potent than iodixanol when expressed in terms of iodine concentration (mg I ml-1), but both agents were equipotent when expressed in terms of molarity (mM). We conclude that relaxation of isolated rabbit aortic rings to iodixanol and iopromide under conditions where there is no fluid flow is endothelium-independent, and therefore not mediated by release of the potent endogeneous nitrovasodilator endothelium-derived relaxing factor (EDRF). Furthermore, their relaxant activity under the in vitro experimental conditions employed is attributable to a direct action on vascular smooth muscle by factors in addition to osmolality, and may depend on features that are not specifically associated with the presence of the iodine atom. PMID- 7881879 TI - Organized chaos? Computed tomographic evaluation of the neuropathic diabetic foot. AB - Accurate radiographic evaluation of diabetic neuroarthropathy is increasingly difficult as the disease becomes more florid. 22 patients with a known diabetic neuroarthropathy of one or both feet were prospectively examined by computed tomography (CT) in the axial and coronal planes. Bilateral changes of a neuroarthropathy were present in 75% of cases. Distinct patterns of disease were seen and categorized into five types in order of increasing severity. Changes at the medial tarsometatarsal joints and adjacent intercuneiform joints were seen in all affected feet. More extensive disease involved the medial arch more commonly than the lateral. Fractures of the tarsal bones were found in 32% of cases and were associated with neuroarthropathic changes in adjacent joints. Calcaneal fractures were seen in four feet. A Lisfranc fracture-dislocation was present in 41% of cases and a bilateral in only 21%. A single CT examination of the foot, while an accurate method of demonstrating the extent of the disease, is an insensitive indicator of disease activity. PMID- 7881880 TI - Idiopathic isosexual central precocious puberty: magnetic resonance findings in 30 patients. AB - The purpose of this prospective study was to define the incidence of magnetic resonance imaging (MRI) abnormalities in the brain in patients with idiopathic central precocious puberty without any additional neurological signs and symptoms, and to evaluate the routine use of gadolinium contrast in these patients. 30 patients (29 girls, one boy; age range 1.9-11.9 years) with idiopathic central precocious puberty were studied. MRI of the brain in axial, coronal and sagittal planes was performed before and after administration of gadopentetate dimeglumine, with special attention to the region of the third ventricle. There are three major findings: (1) the height of the pituitary gland is increased up to adult size compared with normal individuals; (2) in four patients (13%) major structural abnormalities were found; three hamartomas of the tuber cinereum and one gliomatous process extending from the chiasm to the optic tract; and (3) the routine use of gadopentetate dimeglumine did not reveal new abnormalities although the lack of enhancement made a positive contribution to diagnostic certainty. We conclude that contrast enhanced MR examination is a safe and reliable method for the exclusion of abnormalities in children with precocious puberty and for the follow-up of those patients in whom abnormalities are present. PMID- 7881881 TI - Eye splashes during invasive vascular procedures. AB - In recent years there has been an increased awareness among health care workers regarding possible risk of nosocomial transmission of blood borne pathogens. The aim of this study is to document the risk of contamination of radiologists' eyes during invasive vascular procedures. Radiologists performing these examinations were asked to wear glasses throughout. After each examination the glasses were inspected for droplets. 150 procedures were performed on 123 patients (M = 80, F = 43). 10 procedures (6.7%) resulted in splashes to glasses. In four of these cases the radiologist was not aware of the "eye splash" nor was there a spray event to account for it. Radiologists were aware of 13 spray events (8.7% of all procedures). There was a significantly increased risk of spray events and eye splashes during thrombolysis (chi 2 = 14.93, p < 0.001) and of spray events during angioplasty when compared with perfemoral arteriography (chi 2 = 8.816, p < 0.01). Procedures lasting longer than 30 min were associated with a significantly increased risk of spray events (chi 2 = 5.63, p < 0.02). Significantly more eye splashes were associated with more than two catheter changes (chi 2 = 8.912, p < 0.01). It is suggested that protective eye wear should be used routinely during invasive vascular procedures. PMID- 7881882 TI - The application of dose-volume histograms to the Paris and Manchester systems of brachytherapy dosimetry. AB - When the geometry of an implant does not exactly follow a system of dosimetry problems arise in choosing a treatment dose rate. This study has investigated the use of natural dose-volume histograms (DVHs) as a means for choosing the treatment dose level in these cases. A number of ideal geometrical cases have been investigated. For these, where appropriate, the Paris or Manchester dose rates have been calculated and compared with the peak position of the natural DVH. The dose rate at the peak of the DVH was found to agree with the basal dose rate calculated according to the Paris rules. For implants that completely obeyed the Paris rules the mean ratio was 1.009 +/- 4%. A series of clinical implants was also examined. For these the mean ratio was 1.002 +/- 2.5%. It is concluded that the peak position of a DVH can be used to predict the Paris basal dose rate of an implant. There was no systematic relationship found between the Manchester dose rate and the peak position of the DVH. The mean ratio between the Manchester dose rate and the peak dose rate position of the DVH was 0.82 +/- 13% for a series of implants. PMID- 7881883 TI - Models for estimating the risk of ulcers in the small intestine after localized single or fractionated irradiation. AB - Subacute and chronic ulcerations of the intestinal mucosa are important causes of serious complications following radiation therapy for abdominal or pelvic tumours. We describe dose-response models for estimating the risk of mucosal ulcers in the small intestine after uniform, localized single or fractionated (once-daily) X-ray exposure. The models were fitted to data for ulceration incidence, based on a 26 week post-irradiation follow-up of male Sprague-Dawley rats which received a wide range of single and fractionated once-daily 250 kV X ray doses to a short loop (partial volume) of transposed, but functionally intact, small intestine. The models presented for single (Weibull (W)) and fractionated (modified Weibull (MW)) exposures of a partial volume of tissue allow estimation of the risk of radiation-induced injury. While the W model is not new, its adaptation to partial volume irradiation and the MW model are. Isoeffect relationships are presented for the uniform fractional dose Ds(i%) associated with an i% (e.g. 0%, 5%, 10%, 50%) risk of intestinal mucosal ulcers as a function of the number of once-daily dose fractions, where Ds(0%) represents the threshold fractional dose. Although the Ds(5%) and Ds(0%) estimates provided for intestinal mucosal ulcers are based on animal data, the ratio Ds(0%)/Ds(5%) and more generally ratios Ds(j%)/Ds(i%) (where i not equal to j), are presumed to apply to humans. The indicated ratios are predicted to be independent of the partial volume irradiated and the number of once-daily dose fractions, and may be independent of radiation quality. Isoeffect equations are also presented that apply to circumstances where different partial volumes within the same reference volume (i.e. the total volume of tissue considered) receive different doses, but the dose within a given partial volume is uniformly distributed. These isoeffect equations provide a means of converting non-uniform dose within a reference volume to uniform isoeffect dose to the total reference volume and may have applications outside the field of radiation therapy (e.g. evaluating effects of non-uniform exposure of the small intestine or skin by a hot particle). PMID- 7881884 TI - The effects of sublethal damage recovery and cell cycle progression on the survival probability of cells exposed to radioactive sources. AB - Cell progression through the mitotic cycle during low dose rate irradiation may alter notably the survival probability, particularly when a fraction of the dose is delivered during a sensitive phase of the cycle. In this paper we indicate that the consequences of this phenomenon, commonly believed to lead to an "inverse dose rate effect", may be significantly modulated (and even cancelled) as a result of (a) interactions among sublethal lesions produced in different phases of the mitotic cycle, and (b) variations in these lesions' production rates and repair ability from one phase of the cycle to another. The mathematical model presented (and accompanying numerical examples) takes into account the possibility of changes (e.g. radioactive decay) in the dose rate during exposure. PMID- 7881885 TI - The effects of local X-irradiation on the distensibility of the rectum in rats. AB - Proctometry was performed on female Wistar rats following irradiation of the rectum with single doses of 15, 18 and 22 Gy of X-rays. The results indicated a progressive increase in distensibility until week 29 after irradiation which was attributed to degenerative changes in the intestinal wall. A major factor which determines colorectal pressure is the neuromuscular activity, however, neuromuscular transmission was not affected by irradiation. PMID- 7881886 TI - Update on the recommended viewing protocol for FAXIL threshold contrast detail detectability test objects used in television fluoroscopy. AB - The significance of varying the viewing conditions that may affect the perceived threshold contrast of X-ray television fluoroscopy systems has been investigated. Factors investigated include the ambient room lighting and the viewing distance. The purpose of this study is to find the optimum viewing protocol with which to measure the threshold detection index. This is a particular problem when trying to compare the image quality of television fluoroscopy systems in different input field sizes. The results show that the viewing distance makes a significant difference to the perceived threshold contrast, whereas the ambient light conditions make no significant difference. Experienced observers were found to be capable of finding the optimum viewing distance for detecting details of each size, in effect using a flexible viewing distance. This allows the results from different field sizes to be normalized to account for both the magnification and the entrance air kerma rate differences, which in turn allow for a direct comparison of performance in different field sizes. PMID- 7881887 TI - Technical note: an aid to barium meal in the infant. PMID- 7881888 TI - Technical note: low density contrast in upper abdominal computed tomography. AB - We describe the use of a fat-based low density oral contrast agent in computed tomography (CT) of the upper abdomen. It has a CT number of -71 Hounsfield units (HU) and allows excellent visualization of the bowel wall and adjacent structures as well as reducing the artefacts seen with iodinated high density contrast. PMID- 7881889 TI - Case report: oesophageal duplication cyst causing left lung collapse and hypoperfusion. AB - Oesophageal duplication cysts are very rare congenital abnormalities. We report a case of one sited in the middle third of the oesophagus causing stenoses of both pulmonary arteries, with collapse of the left lung due to left main bronchus obstruction. PMID- 7881890 TI - Case report: a hamartoma presenting as a giant oesophageal polyp. AB - Giant oesophageal polyp (GOP) is a very rare intraluminal tumour. It is usually a benign, fibrovascular polyp arising from the proximal third of the oesophagus. We describe a patient with such a polyp but with a histological diagnosis of hamartoma. Regurgitation of the polyp into the mouth, which can lead to asphyxia, is a feared complication. A barium swallow and oesophagoscopy are the common diagnostic procedures. The site of the polyp and its volume often define the method of resection. PMID- 7881891 TI - Case report: renal transplant artery stenosis--three cases where magnetic resonance angiography was superior to conventional arteriography. AB - Stenosis of renal transplant arteries is a common cause of graft dysfunction and hypertension. Conventionally it is investigated by intraarterial digital subtraction angiography (IA DSA). Recently three-dimensional phase contrast magnetic resonance angiography (MRA) has been used successfully as a non-invasive method of assessing renal transplant arteries. We report three cases where MRA was superior to IA DSA in the detection of renal transplant artery stenosis. PMID- 7881892 TI - Case of the month: atlanto-axial rotatory fixation. PMID- 7881893 TI - Hepatocellular carcinoma diagnosed radiologically, treated by transcatheter arterial embolization and limited-field radiotherapy. PMID- 7881894 TI - A scanning and transmission electron microscopic study of the development of the surface structure of neuroepithelial bodies in the mouse lung. AB - Neuroepithelial bodies (NEBs) are groups of neuroepithelial (NE) cells that are localized on mounds on the bronchiolar epithelium of the lung. The present study examined NEBs in mice ranging in age from 2 days before birth to 80 days after birth. The position and surface architecture of NEBs was examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In foetal mice, 2 days before birth, NEBs were distinguished from the rest of the bronchiolar epithelium by a slight elevation of non-ciliated Clara-like cells arranged in a cobblestone-like pattern. The exposed surface of the NEB was identified by small protrusions with regular microvilli intermittently located at the base of deep clefts between the Clara-like cells. The surface of the Clara like cells had fewer and smaller microvilli and could be easily distinguished from the apical surface of the NEB. Before birth, the surface of all of the apical cells was covered by regularly placed microvilli, however after birth some of the more prominently positional apical cells revealed a bare patch at the centre of the portion of apical cell exposed to the lumen of the lung. As the mice aged there was an increase in the number of apical cell protrusions observed with centrally positioned bare patches. These two morphologically distinct surfaces of apical cells may have separate specialized functions. The exposed surfaces of apical cells were often observed in pairs and this feature has been observed in various sensory organs providing support for chemoreceptive function. However small bright spheres resembling vesicles were frequently observed on the lumenal surface of apical cells of the centrally placed bare patch. Transmission electron microscopy confirmed the presence of vesicles on the surface of apical cells and due to their location these vesicles were thought to contain a substance secreted into the lumen of the lung by apical cells. The significance of the bare region on the apical cells is not clear in terms of the proposed chemoreceptive function usually attributed to NEBs. It may be possible that the morphological changes observed in apical cells after birth are more appropriate for secretion of a substance into the lumen of the lung than for chemoreception. This is supported by the observation in the present study of vesicles lying on the lumenal surface of the bare region of the apical cell, however the mechanism for secretion of whole vesicles is not clear and requires further investigation. PMID- 7881895 TI - Double immunogold labelling demonstrating expression of recombinant genes for production of an anti-fertility vaccine. AB - The multiple antibody technique for double immunogold labelling for the simultaneous localization of two antigens with negative staining was utilized to demonstrate the expression of recombinant genes in bacteria, with the primary antibodies being raised in different host species. For the production of a vaccine for immunological control of fertility, a multi-functional plasmid vector was introduced into the bacterium Pseudomonas aeruginosa containing the Dichelobacter nodosus fimbrial subunit gene with a grafted amino acid sequence of luteinizing hormone releasing hormone (LHRH) peptide. Fimbriae of this recombinant, when run on a SDS-polyacrylamide electrophoresis gel, gave a single broad band for LHRH peptide/D. nodosus subunit and were harvested to produce the anti-fertility vaccine which, when injected into mice, produced atrophy of the testes with absence of sperm, resulting in reversible castration. Double immunogold labelling of the recombinant P. aeruginosa bacteria demonstrated fimbriae with strong expression of the LHRH-peptide, expression of the D. nodosus subunit and absence of host fimbriae. PMID- 7881896 TI - Formation of surface membranes in developing mammalian hair fibres. AB - Mammalian hair fibres result from complex mechanisms involving synthesis, assembly and stabilisation of keratin proteins in the follicle. The developing hair shaft consists of outer cuticle cells surrounding cortical and medullary (optional) cell types. Presumptive fibre cuticle (FC) is contained by the inner root sheath (IRS) consisting of IRS cuticle, Huxley and Henle cells which are in turn enclosed in an outer root sheath (ORS) of epidermal-like cells. In the current structural studies we have used energy filtered transmission electron microscopy (Zeiss 902A) on Merino sheep skin biopsies to examine the fine sequence of morphological changes involved in forming the fibre surface membrane and the associated underlying structural bands comprising the a-layer and exocuticle. Prior to the development of the exocuticle, FC cells demonstrate a typical plasma-membrane apposed to IRS cuticle plasma-membranes separated by an intercellular space. The formation of exocuticular lamellae is followed by degradation of the residual FC surface membrane and the appearance of intercellular laminae demonstrating a stained central band. As maturation continues cleavage between IRS cuticle and FC occurs along this central band liberating hair into the pilary canal. The mature surface consists of keratinized cells containing a well developed exocuticle and a-layer coated with paired lamina (presumably two lipid containing bilayers) of material approximately 10-12 nm thick derived from the intercellular laminae. The current observations show FC surface formation is similar to processes occurring in epidermal stratum corneum and that the cuticle surface membrane of mammalian fibres is not derived from a modified plasma-membrane as previously documented. PMID- 7881897 TI - Comparison of immunogold methodologies for the detection of low copy number viral antigens in bluetongue virus (BTV)-infected cells. AB - Cells infected with bluetongue virus (BTV) were prepared for immunocytochemistry by freeze substitution, the progressive lowering of temperature technique and the Tokuyasu method. Sections containing virus-infected cells were incubated with specific monoclonal antibodies and colloidal gold probes to detect virus antigens of varying copy number; these BTV proteins were structural proteins VP2 and VP7 and the non-structural protein NS2. Protocols compared in this study represented those used in laboratories which handle infectious agents and as such, all samples were pre-fixed with minimum concentrations of glutaraldehyde to inactivate the virus. No statistical difference was found between the gold labelling of sections prepared by the progressive lowering of temperature technique and freeze substitution. The results showed that cryo-sections yielded the best signal-to-noise ratio for all proteins examined in this study and were therefore the most sensitive system for the detection of low copy number proteins. The data and associated inferences relate to the system described in this paper and possibly other analogous systems. PMID- 7881898 TI - Levels of mineral nutrients in fresh- and frozen bulk hydrated biological specimens: a comparison of EDS data collected in the environmental SEM and a conventional cryo-SEM. AB - Energy-dispersive X-ray microanalysis (EDS) was compared in fresh- and frozen bulk hydrated tissues using the Environmental SEM (ESEM) and conventional cryo SEM, respectively. Analysis of globoid inclusions of Eucalyptus calophylla seed from two soil types demonstrated that higher levels of cations (K, Ca, Mg, Al, Fe, Mn, Cu, Zn) occurred in seeds from soils containing higher levels of Al, while EDS-detectable levels of S and P were dependent upon the techniques utilised. Cumulative changes in ESEM-EDS-detectable levels of S and P were characterized by collecting cumulative spectra from nutrient standards and compared with those for K. Progressive increases in K occurred and were consistent with an enriching effect. Levels of S and P increased during early analysis (40-60 sec live time) and decreased thereafter. The semi-conductive nature of biological samples, the loss of anions and gain of cations from the net negatively-charged electron interaction volume contributed to an electrochemical bias. These local modifications in fluid chemistry were reversible. Dehydration effects also occurred in stable, 'wet' samples. These differences indicated that EDS in ESEM may be limited to cations rather than anions, and that changes in fluid electrochemistry and dehydration may affect the level and distribution of elements. PMID- 7881899 TI - Negative staining can cause clumping of Bordetella pertussis fimbriae. AB - The state of fimbriae type 2 (Fim 2) and fimbriae type 3 (Fim 3) preparations from Bordetella pertussis were examined by negative stain electron microscopy. Uranyl acetate induced clumping of Fim 3 regardless of pH and was unsuitable as a stain for establishing the state of fimbriae. Both ammonium molybdate and sodium phosphotungstate were able to show the differences in Fim 3 stored at pH 7.2 and pH 9.5. PMID- 7881900 TI - Expression of highly disulfide-bonded proteins in Pichia pastoris. PMID- 7881901 TI - Structure of 3-isopropylmalate dehydrogenase in complex with NAD+: ligand-induced loop closing and mechanism for cofactor specificity. AB - BACKGROUND: The leucine biosynthetic enzyme 3-isopropylmalate dehydrogenase (IMDH) belongs to a unique class of bifunctional decarboxylating dehydrogenases. The two best-known members of this family, IMDH and isocitrate dehydrogenase (IDH), share a common structural framework and catalytic mechanism but have different substrate and cofactor specificities. IMDH is NAD(+)-dependent, while IDHs occur in both NAD(+)-dependent and NADP(+)-dependent forms. RESULTS: We have co-crystallized Thermus thermophilus IMDH with NAD+ and have determined the structure at 2.5 A resolution. NAD+ binds in an extended conformation. Comparisons with the structure in the absence of cofactor show that binding induces structural changes of up to 2.5 A in the five loops which form the dinucleotide-binding site. The adenine and diphosphate moieties of NAD+ are bound via interactions which are also present in the NADP(+)-IDH complex. Amino acids which interact with the NADP+ 2'-phosphate in IDH are substituted or absent in IMDH. The adenosine ribose forms two hydrogen bonds with Asp278, and the nicotinamide and nicotinamide ribose interact with Glu87 and Asp78, all unique to IMDH. CONCLUSIONS: NAD+ binding induces a conformational transition in IMDH, resulting in a structure that is intermediate between the most 'open' and 'closed' decarboxylating dehydrogenase conformations. Physiological specificity of IMDH for NAD+ versus NADP+ can be explained by the unique interaction between Asp278 and the free 2'-hydroxyl of the NAD+ adenosine, discrimination against the presence of the 2'-phosphate by the negative charge on Asp278, and the absence of potential favorable interactions with the 2'-phosphate of NADP+. PMID- 7881902 TI - Comparative analyses of pentraxins: implications for protomer assembly and ligand binding. AB - BACKGROUND: Pentraxins are a family of plasma proteins characterized by their pentameric assembly and calcium-dependent ligand binding. The recent determination of the crystal structure for a member of this family, human serum amyloid P component (SAP), provides a basis for the comparative analysis of the pentraxin family. RESULTS: We have compared the sequences, tertiary structures and quaternary arrangements of SAP with human C-reactive protein (CRP), Syrian hamster SAP (HSAP) and Limulus polyphemus CRP (LIM). These proteins can adopt a beta-jelly roll topology and a hydrophobic core similar to that seen in SAP. Only minor differences are observed in the positions of residues involved in coordinating calcium ions. CONCLUSIONS: Calcium-mediated ligand binding by CRP, HSAP and LIM is similar to that defined by the crystal structure of SAP, but sequence differences in the hydrophobic pocket explain the differential ligand specificities exhibited by the homologous proteins. Differences elsewhere, including insertions and deletions, account for the different (hexameric) quaternary structure of LIM. PMID- 7881903 TI - Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2. AB - BACKGROUND: Growth factor receptor-bound protein 2 (GRB2) is an adaptor protein with three Src homology (SH) domains in the order SH3-SH2-SH3. Both SH3 domains of GRB2 are necessary for interaction with the protein Son of sevenless (Sos), which acts as a Ras activator. Thus, GRB2 mediates signal transduction from growth factor receptors to Ras and is thought to be a key molecule in signal transduction. RESULTS: The three-dimensional structure of the carboxy-terminal SH3 domain of GRB2 (GRB2 C-SH3) was determined by NMR spectroscopy. The SH3 structure consists of six beta-strands arranged in two beta-sheets that are packed together perpendicularly with two additional beta-strands forming the third beta-sheet. GRB2 C-SH3 is very similar to SH3 domains from other proteins. The binding site of the ligand peptide (VPP-PVPPRRR) derived from the Sos protein was mapped on the GRB2 C-SH3 domain indirectly using 1H and 15N chemical shift changes, and directly using several intermolecular nuclear Overhauser effects. CONCLUSIONS: Despite the structural similarity among the known SH3 domains, the sequence alignment and the secondary structure assignments differ. We therefore propose a standard description of the SH3 structures to facilitate comparison of individual SH3 domains, based on their three-dimensional structures. The binding site of the ligand peptide on GRB2 C-SH3 is in good agreement with those found in other SH3 domains. PMID- 7881904 TI - A novel class of winged helix-turn-helix protein: the DNA-binding domain of Mu transposase. AB - BACKGROUND: Mu transposase (MuA) is a multidomain protein encoded by the bacteriophage Mu genome. It is responsible for translocation of the Mu genome, which is the largest and most efficient transposon known. While the various domains of MuA have been delineated by means of biochemical methods, no data have been obtained to date relating to its tertiary structure. RESULTS: We have solved the three-dimensional solution structure of the DNA-binding domain (residues 1 76; MuA76) of MuA by multidimensional heteronuclear NMR spectroscopy. The structure consists of a three-membered alpha-helical bundle buttressed by a three stranded antiparallel beta-sheet. Helices H1 and H2 and the seven-residue turn connecting them comprise a helix-turn-helix (HTH) motif. In addition, there is a long nine-residue flexible loop or wing connecting strands B2 and B3 of the sheet. NMR studies of MuA76 complexed with a consensus DNA site from the internal activation region of the Mu genome indicate that the wing and the second helix of the HTH motif are significantly perturbed upon DNA binding. CONCLUSIONS: While the general appearance of the DNA-binding domain of MuA76 is similar to that of other winged HTH proteins, the connectivity of the secondary structure elements is permuted. Hence, the fold of MuA76 represents a novel class of winged HTH DNA binding domain. PMID- 7881905 TI - The three-dimensional structure of PNGase F, a glycosylasparaginase from Flavobacterium meningosepticum. AB - BACKGROUND: Peptide:N-glycosidase F (PNGase F) is an enzyme that catalyzes the complete removal of N-linked oligosaccharide chains from glycoproteins. Often called an endoglycosidase, it is more correctly termed an amidase or glycosylasparaginase as cleavage is at the asparagine-sugar amide linkage. The enzyme is widely used in structure-function studies of glycoproteins. RESULTS: We have determined the crystal structure of PNGase F at 1.8 A resolution. The protein is folded into two domains, each with an eight-stranded antiparallel beta jelly roll configuration similar to many viral capsid proteins and also found, in expanded form, in lectins and several glucanases. Two potential active site regions have been identified, both in the interdomain region and shaped by prominent loops from one domain. Exposed aromatic residues are a feature of one site. CONCLUSIONS: The finding that PNGase F is based on two jelly roll domains suggests parallels with lectins and other carbohydrate-binding proteins. These proteins either bind sugars on the concave face of the beta-sandwich structure (aided by loops) or amongst the loops themselves. Further analysis of the function and identification of the catalytic site should lead to an understanding of both the specificity of PNGase F and possibly also the recognition processes that identify glycosylation sites on proteins. PMID- 7881906 TI - Mechanistic implications and family relationships from the structure of dethiobiotin synthetase. AB - BACKGROUND: Biotin is the vitamin essential for many biological carboxylation reactions, such as the conversion of acetyl-coenzyme A (CoA) to malonyl-CoA in fatty acid biosynthesis. Dethiobiotin synthetase (DTBS) facilitates the penultimate, ureido ring closure in biotin synthesis, which is a non-biotin dependent carboxylation. DTBS displays no sequence similarity to any other protein in the database. Structural studies provide a molecular insight into the reaction mechanism of DTBS. RESULTS: We present the structure of DTBS refined to 1.80 A resolution with an R-factor of 17.2% for all terms plus unrefined data on the binding of the substrate, 7,8-diaminopelargonic acid and the product, dethiobiotin. These studies confirm that the protein forms a homodimer with each subunit folded as a single globular alpha/beta domain. The presence of sulphate ions in the crystals and comparisons with the related Ha-ras-p21 oncogene product are used to infer the ATP-binding site, corroborated by the difference electron density for the ATP analogue AMP-PNP. CONCLUSIONS: This study establishes that the enzyme active site is situated at the dimer interface, with the substrate binding to one monomer and ATP to the other. The overall fold of DTBS closely resembles that of three other enzymes, adenylosuccinate synthetase (purA), Ha-ras p21, and nitrogenase iron protein, that are unrelated by sequence or function, indicating that DTBS is a member of a diverse family of enzymes. PMID- 7881907 TI - The three-dimensional structure of glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroides refined at 2.0 A resolution. AB - BACKGROUND: Glucose 6-phosphate dehydrogenase (G6PD) is the first enzyme of the pentose phosphate pathway. Normally the pathway is synthetic and NADP-dependent, but the Gram-positive bacterium Leuconostoc mesenteroides, which does not have a complete glycolytic pathway, also uses the oxidative enzymes of the pentose phosphate pathway for catabolic reactions, and selects either NAD or NADP depending on the demands for catabolic or anabolic metabolism. RESULTS: The structure of G6PD has been determined and refined to 2.0 A resolution. The enzyme is a dimer, each subunit consisting of two domains. The smaller domain is a classic dinucleotide-binding fold, while the larger one is a new beta+ alpha fold, not previously seen, with a predominantly antiparallel nine-stranded beta sheet. There are significant structural differences in the coenzyme-binding domains of the two subunits, caused by Pro 149 which is cis in one subunit and trans in the other. CONCLUSIONS: The structure has allowed us to propose the location of the active site and the coenzyme-binding site, and suggests the role of many of the residues conserved between species. We propose that the conserved Arg46 would interact with both the adenine ring and the 2'-phosphate of NADP. Gln47, which is not conserved, may contribute to the change from NADP to dual coenzyme specificity. His178, in a nine-residue peptide conserved for all known sequences, binds a phosphate in the active site pocket. His240 is the most likely candidate for the base to oxidize the 1-hydroxyl group of the glucose 6-phosphate substrate. PMID- 7881908 TI - Old yellow enzyme at 2 A resolution: overall structure, ligand binding, and comparison with related flavoproteins. AB - BACKGROUND: Old yellow enzyme (OYE) was the first flavoenzyme purified, but its function is still unknown. Nevertheless, the NADPH oxidase activity, the flavin mononucleotide environment and the ligand-binding properties of OYE have been extensively studied by biochemical and spectroscopic approaches. Full interpretation of these data requires structural information. RESULTS: The crystal structures of oxidized and reduced OYE at 2 A resolution reveal an alpha/beta-barrel topology clearly related to trimethylamine dehydrogenase. Complexes of OYE with p-hydroxybenzaldehyde, beta-estradiol, and an NADPH analog show all three binding at a common site, stacked on the flavin. The putative NADPH binding mode is novel as it involves primary recognition of the nicotinamide mononucleotide portion. CONCLUSIONS: This work shows that the striking spectral changes seen upon phenol binding are due to close physical association of the flavin and phenolate. It also identifies the structural class of OYE and suggests that if NADPH is its true substrate, then OYE has adopted NADPH dependence during evolution. PMID- 7881909 TI - Structure of the catalytic core of the family F xylanase from Pseudomonas fluorescens and identification of the xylopentaose-binding sites. AB - BACKGROUND: Sequence alignment suggests that xylanases evolved from two ancestral proteins and therefore can be grouped into two families, designated F and G. Family F enzymes show no sequence similarity with any known structure and their architecture is unknown. Studies of an inactive enzyme-substrate complex will help to elucidate the structural basis of binding and catalysis in the family F xylanases. RESULTS: We have therefore determined the crystal structure of the catalytic domain of a family F enzyme, Pseudomonas fluorescens subsp. cellulosa xylanase A, at 2.5 A resolution and a crystallographic R-factor of 0.20. The structure was solved using an engineered catalytic core in which the nucleophilic glutamate was replaced by a cysteine. As expected, this yielded both high-quality mercurial derivatives and an inactive enzyme which enabled the preparation of the inactive enzyme-substrate complex in the crystal. We show that family F xylanases are eight-fold alpha/beta-barrels (TIM barrels) with two active-site glutamates, one of which is the nucleophile and the other the acid-base. Xylopentaose binds to five subsites A-E with the cleaved bond between subsites D and E. Ca2+ binding, remote from the active-site glutamates, stabilizes the structure and may be involved in the binding of extended substrates. CONCLUSIONS: The architecture of P. fluorescens subsp. cellulosa has been determined crystallographically to be a commonly occurring enzyme fold, the eight-fold alpha/beta-barrel. Xylopentaose binds across the carboxy-terminal end of the alpha/beta-barrel in an active-site cleft which contains the two catalytic glutamates. PMID- 7881910 TI - Favoured structural motifs in globular proteins. AB - While many different structural motifs have been observed to recur within globular proteins, only some of the motifs exhibit unique handedness and a unique overall fold. PMID- 7881912 TI - Ultrastructural studies of early mouse embryos obtained by oocyte fusion. AB - Oocyte fusion induced by inactivated Sendai virus results in the production of 'zygotes' that are able to undergo the first stages of embryonic development. The oocyte fusion products (OFP) obtained follow a morphological developmental pattern equivalent to that of control embryos, at least up to the 8-cell stage. The percentage of OFP that reach the 8-cell stage is extremely low (3%) compared with control embryos cultured in vitro (95%). On light microscopy, the OFP obtained show morphological characteristics identical to control embryos, although their cell diameters are larger. The cortical reaction, meiotic reactivation, extrusion of second polar bodies and pronucleus formation take place as observed in controls. The ultrastructural characteristics of oocyte fusion products at the 1-, 2-, 4- and 8-cell stages are analogous to those of controls, including the presence of structures related to the activation of the embryo genome. However some differences concerning cell ultrastructure, mainly in the nucleus, are observed and discussed in the text. PMID- 7881911 TI - Fertilisation in sea urchins: how many different molecules are involved in gamete interaction and fusion? AB - It has been established that fertilisation in the sea urchin involves binding of acrosome-reacted sperm to an egg cell surface receptor. The structure and function of this receptor, as well as the possible involvement of other cell surface molecules in the binding, fusion and activation events, is discussed. PMID- 7881913 TI - Isolation and microinjection of active sperm nuclei into egg cells and central cells of isolated maize embryo sacs. AB - Artificial fertilisation was attempted in maize by microinjecting sperm nuclei into the egg cell or central cell of isolated embryo sacs. A protocol for isolation of nuclei from pollen grains was developed and a pure fraction of sperm nuclei was obtained after centrifugation on a Percoll gradient. The in vitro transcriptional activity of the nuclei was tested by incorporation of radioactive UTP into RNA. The level of labelled nucleotide incorporation increased and reached a maximum after between 30 and 40 min in the incubation medium. The embryo sacs were enzymatically isolated and their viability determined by observation of cytoplasmic streaming in the female cells. The embryo sacs were immobilised by embedding in low-melting-point agarose and a single male nucleus was injected with a bevelled microcapillary. The presence of the injected nucleus in the egg or central cell was demonstrated using a cytological approach. This paper presents an alternative method for studying the intimate processes of fertilisation in plants. PMID- 7881914 TI - Confocal ratio-imaging of intracellular pH in unfertilised mouse oocytes. AB - Unfertilised mouse oocytes absorbed the pH-sensitive fluoroprobe SNARF-1-AM (carboxyseminaph-thorhodafluor-1-acetoxymethylester), the ester being hydrolysed by an intracellular esterase. Ratio-imaging of oocytes containing the resultant SNARF-1 excited by laser light (514 nm) has been obtained by scanning confocal microscopy with appropriate barrier filters to monitor emission maxima about 590 and 640 nm recorded simultaneously in separate channels of the framestore. Images produced by pixel-by-pixel division of these channel images showed uniform distribution of SNARF-1 in equatorial regions in most cells. However, in some oocytes regions (about 4 microns diameter) with smaller ratios (i.e. lower pHi) were detected. The relation between the ratio of emitted maxima and the extracellular pH (pHo) in the presence of nigericin allowed a calibration procedure to determine the intracellular pH (pHi). With this method pHi was estimated to be 7.13 +/- 0.05 (mean +/- SEM, n = 31). Whereas the application of a weak acid (butyric) caused a fall in the ratio and hence in pHi, exposure to weak bases (NH4Cl or trimethylamine) caused a rise. Large changes in pHo did not evoke corresponding changes in the ratio and hence in pHi. Addition of 5% CO2 to the external solution buffered at the usual value of pH 7.4, however, did cause a fall in the ratio which was reversible only when HCO3- was present in the external solution. PMID- 7881915 TI - Methylation in fertilised and parthenogenetic preimplantation mouse embryos. AB - DNA methylation is one of the proposed biochemical mechanisms involved in cell differentiation and in genomic imprinting, and DNA methyltransferase (DMT) is a key enzyme in the embryo since mutation of its gene is lethal early in development. In order to verify that non-viability of uniparental embryos was not due to a defect in the regulation of DMT activity, we compared the metabolism of methylation in parthenogenetic embryos (maternal genome) and in fertilised embryos (maternal and paternal genomes). As regards total methylation, estimated by a measure of S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH) formation, no significant difference was found between the two kinds of embryos during preimplantation development. Mean values were 4.5 +/- 0.6 fmol (SAM+SAH)/h per 2-cell embryo and 0.40 +/- 0.05 fmol SAH/h per 2-cell embryo, i.e. a SAH/(SAM+SAH) ratio of 9%; there was no detectable SAH formation in blastocysts. The same observation can be made for DMT activity, with mean values of: 7.8 fmol/h per oocyte, 8.5 fmol/h per 2-cell embryo, 6.1 fmol/h per 4-cell embryo, 4.1 fmol/h per morula, and no detectable activity in blastocysts. Total methylation as well as DNA methylation is characterised by a progressive drop in activity during preimplantation development. PMID- 7881916 TI - Localisation and capacitation-dependent loss of buffalo sperm-coating antigens shared with rat sperm. AB - The heterodimeric sperm-coating protein CFS was previously localised on the middle-piece region of rat spermatozoa by anti-CFS rabbit antibodies. CFS immunorelated antigens were detected in the secretion of the water buffalo seminal vesicle by protein electrophoresis and Western blotting. Spermatozoa from buffalo epididymal cauda were incubated with the rat antigen and, upon immunostaining with anti-CFS antibodies and goat anti-rabbit fluorescein isothiocyanate (FITC)-conjugated IgGs, CFS was found attached on both the post acrosomal region and the tail. Indirect immunofluorescence analysis permitted the localisation of CFS-related antigens on the same domains of buffalo ejaculated spermatozoa. These results suggest that the buffalo antigens not only share some epitopes with the homologous rat antigen but may also have some of its functional properties. Ejaculated spermatozoa were capacitated in vitro and then assayed for their content of CFS-like antigens. An inverse relationship was found between the levels of capacitation and the amounts of antigens detected, thus suggesting that the in vitro treatment was effective at removing CFS-related proteins from the cell surface. Titration of these proteins to monitor plasma membrane changes during sperm manipulation or to evaluate sperm quality is proposed. PMID- 7881917 TI - Mammalian follicle-stimulating hormone stimulates DNA synthesis in secondary spermatogonia and Sertoli cells in organ culture of testes fragments from the newt, Cynops pyrrhogaster. AB - We previously showed in organ culture of testes fragments from Cynops pyrrhogaster that mammalian follicle-stimulating hormone (FSH) stimulates secondary spermatogonia to differentiate into primary spermatocytes. In this report, we demonstrate in organ culture that FSH stimulates DNA synthesis in secondary spermatogonia and Sertoli cells: the numbers of secondary spermatogonia and Sertoli cells incorporating 5-bromo-2'-deoxyuridine (BrdU) throughout the culture period in the presence of FSH were 3-5 times those incorporating BrdU in the absence of FSH. Moreover, addition of FSH to testes fragments which had become quiescent after a week of culture in the absence of FSH, induced after a day a remarkable increase in the number of spermatogonia and Sertoli cells incorporating BrdU. The above results indicate that FSH stimulates and induces DNA synthesis in spermatogonia and Sertoli cells. Most of the spermatogonia within a cyst were labelled simultaneously and at the same density, indicating that they underwent synchronous DNA synthesis, whereas all the Sertoli cells within a cyst were not labelled simultaneously, indicating that they synthesised DNA asynchronously. When testes fragments pulse-labelled with BrdU were cultured in FSH for 14 days, the secondary spermatogonia differentiated into primary spermatocytes, whereas in the absence of FSH they failed to differentiate and most died by the 7th day. The above results together show that FSH is required for the proliferation of both secondary spermatogonia and Sertoli cells as well as the differentiation of secondary spermatogonia into primary spermatocytes. PMID- 7881918 TI - Confocal image analysis of spatial variations in immunocytochemically identified calmodulin during pollen hydration, germination and pollen tube tip growth in Nicotiana tabacum L. AB - Using monoclonal anti-calmodulin antibodies in conjunction with confocal scanning laser microscopy we have analysed the spatial variations in the distribution pattern of calmodulin (CaM) during the sequential events of pollen hydration, germination and tube growth in Nicotiana tabacum. These immunocytochemical observations have been complemented by immunochemical studies wherein the anti calmodulin antibody raised against pea CaM recognises a polypeptide of c. 18 kDa in the pollen extracts. Digitisation of confocally acquired optical sections of immunofluorescence images reveals that in hydrated pollen a high level of CaM is consistently present in the region of the germinal apertures. Subsequently, with the onset of germination a high CaM concentration was found associated with the plasma membrane of the germination bubble and in the cytoplasm in its vicinity, while in the vegetative cytoplasm a weak diffuse and intense punctate signal was registered. CaM immunostain was also detected in association with the plasma membrane of the tube tips in both short and long pollen tubes. Furthermore, the cytosol of the tubes invariably manifested an apically focused CaM gradient. We were, however, unable to detect any vacuolar association of CaM in the older regions of the pollen tubes. Although punctate immunostain was obvious across the pollen tube numerous punctate structures were invariably present in the extreme tip. The possible implications of these findings in development of cell polarity, polarised growth, maintenance of calcium homeostasis and CaM interactions with other mechanochemical motor proteins in effecting propulsion of organelles during pollen hydration, germination and pollen tube growth are discussed. PMID- 7881919 TI - The role of exogenous energy substrates in blastocoele fluid accumulation in the rat. AB - Preimplantation mammalian development culminates in the formation of a fluid filled cavity, the blastocoele, which is a prerequisite for successful implantation and further development. The blastocoele is enclosed by a single layer of polarised cells, the trophectoderm, which is the first epithelium formed in development. In embryos of the mouse and the rabbit, a basolaterally located Na+/K(+)-ATPase hydrolyses ATP to drive the vectorial transport of ions, which is responsible for the accumulation of blastocoele fluid. Using non-invasive assays of energy substrate consumption and blastocoele fluid accumulation, experiments were carried out on single preimplantation rat embryos, to establish: (1) the roles of the Na+/K(+)-ATPase and exogenous energy substrates, and (2) the relationship between the consumption and metabolism of energy substrates and fluid accumulation, during blastocoele cavity formation in this species. Ouabain 0.5 mM and energy-substrate-free medium both caused an inhibition in the number of embryos forming a blastocoele in culture, and also reduced the rate of fluid accumulation by day 5 blastocysts collapsed in cytochalasin-D and allowed to re expand. Ouabain also reduced the consumption of glucose (but not pyruvate) and the production of lactate by re-expanding blastocysts. In the absence of the inhibitor, a direct relationship was seen between fluid accumulation and both glucose (but not pyruvate) consumption and lactate production. However, ouabain had no effect on intact, expanded blastocysts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7881920 TI - The parental origin of the distal pronucleus in dispermic human zygotes. AB - The purpose of this investigation was to determine the parental origin of the pronucleus furthest from the second polar body (the distal pronucleus) in dispermic human zygotes. Intact dispermic embryos (n = 53) and those from which the distal pronucleus (n = 50) was removed at the zygote stage were biopsied after cleavage. Blastomeres were sexed using either coamplification of X and Y probes using a duplex polymerase chain reaction (PCR), or simultaneous fluorescence in situ hybridisation (FISH) with directly fluorochrome-labelled probes for chromosomes X, Y and 18. The ratio X/Y was determined in both groups of embryos by assessing a minimum of two blastomeres. If the pronuclei in dispermic zygotes are topographically in a fixed position, the X/Y ratio should change from 1:3 in dispermic embryos to 1:1 in enucleated ones. The ratio of embryos containing only an X chromosome and those with X as well as Y chromosomes in the intact dispermic zygotes was 1.0:2.3 which is similar to the theoretical ratio of 1:3. This ratio was 1.0:1.3 in dispermic zygotes from which the distal pronuclei were removed. This ratio is not significantly different from the 1:1 ratio based on a statistical analysis with a sample size of 50. These sex ratios would have been considered different if more than 200 enucleations had been performed. Although the ratio X/Y was altered following removal of distal pronuclei, suggesting frequent targeting of male pronuclei, accidental removal of the female pronucleus could not be excluded. This indicates that enucleation of dispermic zygotes could produce high yields of gynogenetic and androgenetic embryos for research purposes. Clinical application aimed at producing biparental zygotes may be hazardous, since mosaicism was common among enucleated embryos. PMID- 7881921 TI - The spindle apparatus in early embryonic divisions of Ephestia kuehniella Z. (Pyralidae, Lepidoptera) is formed by alignment of minispindles. AB - Spindles were isolated from deposited eggs of the Mediterranean mealmoth, Ephestia kuehniella. Their structure and development were studied using anti tubulin immunofluorescence. The microtubules were labelled with three different monoclonal antibodies. These were directed against beta-tubulin, tyrosinated alpha-tubulin and acetylated alpha-tubulin. Significant differences in the staining behaviour were not detected with the three antibodies. An unusual mode of spindle formation was observed during the first mitotic division after fusion of the pronuclei. Several of the ensuing embryonic divisions may show the same phenomenon. Prophase of these divisions was characterised by an irregular arrangement of microtubules in the nuclear area. The microtubular mass in the nuclear area increased concomitantly with chromosome condensation. Microtubular foci, comparable to the forming asters of canonical spindles, were not detected. The formation of an orderly pattern in the microtubule mass was signalled by the appearance of minispindles apparently developing around individual chromosomes. Several minispindles subsequently aligned and formed metaphase-like entities within the nuclear area. The metaphase-like entities, in turn, aligned with one another and gave rise to a conventional bipolar metaphase spindle with small asters. The further development of the spindle was conventional. The chromosomes migrated towards the spindle poles and finally daughter nuclei formed. The anaphase and telophase spindles possessed both a prominent array of interzone microtubules and asters. The events in prophase of early embryonic mitosis of E. kuehniella may represent a rare case of chromosome-induced spindle formation. PMID- 7881922 TI - Pathophysiology of laparoscopy. PMID- 7881923 TI - Gastric carcinoma in patients over 70 years of age. AB - The clinicopathological features and prognosis of gastric cancer in 344 patients aged 70 years or older who underwent gastrectomy between 1965 and 1990 were determined. Over the years the mean size of the tumour decreased, differentiated tumour tissue was more common, depth of penetration was less prominent, lymphatic and vascular involvement was less frequent, and the rate of lymph node metastasis and peritoneal dissemination decreased. Extensive lymph node dissection was more frequently carried out and the rate of curative resection rose. Survival rates improved with early detection of gastric cancer and there was no increase in operative morbidity and mortality rates. As age alone is not a contraindication to surgery for patients with gastric carcinoma, early detection of the lesion and surgical treatment are expected to increase the survival of elderly patients with this malignancy. PMID- 7881924 TI - Intraoperative laparoscopic diagnosis of contralateral patent processus vaginalis in children with unilateral inguinal hernia. AB - The contralateral internal ring of 96 children was examined laparoscopically during unilateral hernia repair to minimize the chance of development of contralateral hernia. Laparoscopy was performed through the hernia sac before ligation. Of 29 patients with positive laparoscopic findings, 28 had a patient processus vaginalis as confirmed by simultaneous contralateral exploration and there was one false positive. Patency of the contralateral processus vaginalis was found in 28 (29 per cent) of the 96 patients. Children under 2 years of age had a significantly higher incidence of patent contralateral processus vaginalis than older patients. The only complication of the procedure was wound infection in two patients. This is a simple, safe and accurate procedure to select children for contralateral surgical exploration. PMID- 7881925 TI - Colonic necrosis is an adverse prognostic factor in pancreatic necrosis. PMID- 7881927 TI - Application of three-dimensional spiral computed tomographic angiography to pancreatoduodenectomy for cancer. PMID- 7881926 TI - Treatment and survival in 13,560 patients with pancreatic cancer, and incidence of the disease, in the West Midlands: an epidemiological study. AB - The trends in treatment and outcome of 13,560 patients with pancreatic cancer, and in incidence of the disease, in the West Midlands health region were determined between 1957 and 1986 using data from the West Midlands Region Cancer Registry. Patients were divided into those diagnosed in the first 20 years (1957 1976, n = 7888) and the most recent 10 years (1977-1986, n = 5672). The disease was more common in men and the incidence increased up to 1970 after which it levelled off. In the 1977-1986 period a lower proportion of patients had laparotomy alone (825 (14.5 per cent) versus 1552 (19.7 per cent)), a similar proportion had bypass surgery (2010 (35.4 per cent) versus 2760 (35.0 per cent)), while a greater proportion had supportive care (2710 (47.8 per cent) versus 3368 (42.7 per cent)) but the resection rates were the same (145 (2.6 per cent) versus 208 (2.6 per cent)). The 30-day mortality rates between the two periods improved for resection (40 (27.6 per cent) versus 94 (45.2 per cent)), bypass surgery (436 (21.7 percent) versus 691 (25.0 per cent)) and laparotomy (372 (45.1 per cent) versus 873 (56.3 per cent)). The 12-month survival rate for bypass did not significantly differ during the study (14.9 per cent versus 12.4 per cent) but there was a significant improvement in the 5-year survival for resection (9.7 per cent versus 2.6 per cent, P < 0.015). The resection rates were low and 30-day mortality rates for surgery were high compared with those of other published series. PMID- 7881928 TI - Liver transplantation in patients with fulminant hepatic failure. AB - Fulminant hepatic failure without liver transplantation is associated with a high mortality rate (80-100 per cent). Some 254 liver transplantations were performed on 202 patients between April 1986 and February 1992. Of these, 26 patients had fulminant hepatic failure. The median age was 31.5 (range 3-60) years. Reduced size grafts were used in seven patients. The preoperative mortality rate was six of 26 patients, and five patients died during follow-up. Ten patients underwent retransplantation and two a second retransplant. The overall mortality rate was 16 of 26 and actuarial survival rate was 62.7 per cent at 12 months and 48.7 per cent at 36 months. The preoperative mortality rate is relatively high but liver transplantation is currently recommended as a last-resort treatment for patients with fulminant hepatic failure in the absence of response to medical treatment. PMID- 7881930 TI - Combined pulmonary tumour embolectomy and extended right hepatectomy with inferior vena cava resection for advanced hepatocellular carcinoma. PMID- 7881929 TI - Preoperative transcatheter arterial chemoembolization for resectable large hepatocellular carcinoma: a reappraisal. AB - Transcatheter arterial chemoembolization (TACE) improves the treatment of hepatocellular carcinoma (HCC) by causing tumour necrosis and shrinkage. Fifty two patients with resectable large HCC (defined as a maximal tumour diameter of 10 cm or more) were prospectively randomized into two groups: group 1 comprised 24 patients who had 1-5 sessions of TACE before operation; group 2 consisted of the other 28 patients, on whom surgery was performed without delay. Tumour volume was reduced to a mean (s.d.) of 42.8 (15.3) per cent in 16 patients in group 1, but remained unchanged in four and increased in size in a further four. Patients in group 1 had a slightly longer operating time (5.5 versus 4.6 h, P = 0.09), a higher rate of concomitant resection of adjacent organs (58 versus 25 per cent, P = 0.03) and a higher rate of histological invasion to these organs (33 versus 4 per cent, P = 0.01). No difference was found between the two groups in operative blood loss, operative morbidity and mortality rates, and pathological staging. The disease-free survival rate in the two groups was similar, but the incidence of extrahepatic cancer recurrence was higher in group 1 (57 versus 23 per cent, P = 0.03). The actuarial survival rate was also significantly worse in group 1 when determined from the time of detection of the tumour (P = 0.03) or from operation (P = 0.01). It is concluded that preoperative TACE for resectable large HCC should be avoided because it does not provide complete necrosis in large tumours and results in delayed surgery and difficulty in the treatment of recurrent lesions, without any benefit. PMID- 7881931 TI - Tumour growth stimulation after partial hepatectomy can be reduced by treatment with tumour necrosis factor alpha. AB - This study investigated whether partial hepatectomy enhances the growth of experimental liver metastases of colonic carcinoma in rats and whether treatment with recombinant human tumour necrosis factor (TNF) alpha can reduce this increased growth. Resection of 35 or 70 per cent of the liver was performed in inbred WAG rats, with sham-operated controls (five to eight animals per group). Immediately after surgery 5 x 10(5) CC531 colonic tumour cells were injected into the portal vein. After 28 days the animals were killed and the number of liver metastases counted. A 35 per cent hepatectomy induced a significant increase in the median number of liver metastases (28 versus 3 in controls), whereas a 70 per cent resection provoked excessive growth, consistently leading to more than 100 liver metastases and a significantly increased wet liver weight in all animals. TNF-alpha was given intravenously to rats following 70 per cent hepatectomy or sham operation in a dose of 160 micrograms/kg three times per week. This had only a marginal effect on tumour development in sham-operated rats but was very effective following partial hepatectomy (median 45 liver metastases). These observations confirm previous findings that surgical metastasectomy may act as a 'double-edged sword' by provoking outgrowth of dormant tumour cells and suggest that adjuvant treatment with TNF-alpha may be of benefit in patients undergoing resection of metastases. PMID- 7881932 TI - Carcinoid tumour presenting as a giant hepatic cyst. PMID- 7881933 TI - Colour Doppler ultrasonographic imaging in the diagnosis of popliteal artery entrapment syndrome. PMID- 7881934 TI - Preoperative endoscopic drainage for malignant obstructive jaundice. PMID- 7881935 TI - Perioperative and postoperative tranexamic acid reduces the local wound complication rate after surgery for breast cancer. PMID- 7881936 TI - Laparotomy in patients infected with human immunodeficiency virus: indications and outcome. PMID- 7881937 TI - Pain following laparoscopic rectopexy. PMID- 7881938 TI - Elbow arteriovenous fistulas for chronic haemodialysis. PMID- 7881939 TI - Transient femoral nerve palsy complicating preoperative ilioinguinal nerve blockade for inguinal herniorrhaphy. PMID- 7881940 TI - Ischaemic colitis induced by cocaine abuse. PMID- 7881942 TI - Liver resection with total vascular exclusion for malignant tumours. PMID- 7881941 TI - Laparoscopic cholecystectomy for the left-handed surgeon. PMID- 7881943 TI - Juvenile polyposis. AB - Juvenile polyposis is an uncommon condition characterized by the development of multiple juvenile polyps, predominantly in the colon but also in the rest of the gastrointestinal tract. The condition usually presents in childhood; only 15 per cent of patients present as adults. The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse. The more common form of juvenile polyposis (affecting the colon, stomach and small bowel) occurs in the first or second decade with rectal bleeding and anaemia. A family history of the condition is found in 20-50 per cent of patients with apparently an autosomal dominant trait. The gene for juvenile polyposis has not yet been identified. Epithelial dysplasia is common and the cumulative risk of colorectal cancer is > 50 per cent. Various extracolonic abnormalities may also occur. Most patients are treated surgically for colonic polyps, although endoscopic polypectomy is also an option. The rest of the gastrointestinal tract should be screened as should asymptomatic first-degree relatives. PMID- 7881944 TI - Influence of temporary faecal diversion on long-term survival after curative surgery for colorectal cancer. AB - Experimental carcinogenesis is enhanced at colorectal anastomoses, inhibited by proximal faecal diversion and promoted by the closure of a defunctioning stoma. The clinical relevance of these observations was investigated in a retrospective study of curative restorative resection for colorectal carcinoma. The 5-year disease-free survival rate (95 per cent confidence interval) in 122 patients with a temporary stoma (50.4 (41.1-59.7) per cent) was significantly reduced (P < 0.01) compared with that in 218 with no stoma (66.8 (59.4-73.5) per cent). In patients with Dukes B tumours early stoma closure (within 3 months of resection) was associated with a worse survival (P < 0.005) and a higher tumour recurrence rate (P < 0.05) than in those with no stoma. Survival rates after late stoma closure were no different from those in patients with no stoma. Multivariate analysis revealed Dukes stage (P < 0.0001), tumour differentiation (P = 0.02) and timing of stoma closure (P = 0.02) as independent predictors of survival. In curative surgery for colorectal cancer temporary faecal diversion confers a survival disadvantage that can be prevented by delayed closure of the stoma. PMID- 7881945 TI - Laparoscopy in colorectal surgery: a call for careful appraisal. PMID- 7881946 TI - Restoration of intestinal continuity following Hartmann's procedure: the Lothian experience 1987-1992. AB - Restoration of intestinal continuity following Hartmann's procedure is associated with high morbidity (anastomotic leak rates 4-16 per cent) and mortality (0-4 per cent) rates. A total of 178 patients, under the care of seven different surgical units, underwent reversal of Hartmann's procedure during a 5-year period, representing the largest series yet reported. The mortality rate of the study group was 0.6 per cent, the anastomotic leak rate was 3.9 per cent and the incidence of anastomotic stricture was 6.7 per cent. The median time interval between resection and reversal was 92 days and no relation was found between timing and complications. Anastomotic stricture occurred significantly more commonly in stapled than in sutured anastomoses (P < 0.05); however, leaks were equally common in both types. The mean age of the patients who developed major complications was not statistically different from that of the rest of the study group and there was no difference in premorbid state. The authors believe that the low complication rates reported in this series may be attributable to the high level of operator experience in performing this technically difficult procedure, which was done by a consultant in 66 per cent of cases and by a senior registrar in 33 per cent. PMID- 7881947 TI - Pathogenesis and prevention of adhesion formation. PMID- 7881948 TI - Inflammatory pseudotumour in Meckel's diverticulum producing intussusception. PMID- 7881949 TI - Persistence of idiopathic anal fistula may be related to epithelialization. AB - Anal fistulas may fail to heal because of continuing disease within the intersphincteric anal glands. Histological studies of the intersphincteric component of 18 consecutive idiopathic anal fistulas show that fistula persistence may be caused by epithelialization of the fistula track from internal or external openings. Some fistulas are lined by epithelium similar to that of anal gland ducts, but this may also represent epithelium derived from the transitional zone of the anal canal. Persistence may be related more to non specific epithelialization of the track than to a chronically infected anal gland. PMID- 7881950 TI - New procedure for relief of malignant obstruction of the left colon. PMID- 7881951 TI - Spontaneous rupture of an infantile umbilical hernia. PMID- 7881953 TI - Surgical management of thoracic manifestations in human immunodeficiency virus positive patients: indications and results. AB - The records of 97 patients with thoracic complications of human immunodeficiency virus (HIV) were analysed to determine the reasons for surgery and the results of these procedures. Of the patients, 79 underwent surgery; the remaining 18 were managed non-surgically. A total of 36 procedures were performed for diagnostic purposes: mediastinoscopy (21 patients), lung biopsy (15 patients). Therapeutic procedures were performed in 61 patients to treat pneumothorax (23 cases) or empyema thoracis (18 cases), for resection of pulmonary lesions (13 cases), and to treat various other pathologies (seven cases). Ten patients died in hospital: seven after surgery and three after a nonsurgical procedure. Eleven patients developed a postoperative complication. Hospital mortality varied from 0 per cent to 20 per cent, depending on the procedure. The mortality rate appears to be linked to the stage of HIV infection at the time of therapy rather than to the type of procedure performed. Surgical decisions must take into account the patient's Centers for Disease Control stage and physiological status, therapeutic possibilities, and the prognosis of the pathology requiring treatment. PMID- 7881952 TI - Butyrate metabolism in the terminal ileal mucosa of patients with ulcerative colitis. AB - The rate of oxidation of butyrate, glutamine and glucose was investigated in terminal ileal mucosal biopsy samples from nine patients with ulcerative colitis undergoing restorative proctocolectomy and from 12 patients undergoing laparotomy for reasons other than ulcerative colitis. Substrate oxidation was assayed using a radiolabelled isotope technique. Butyrate was the preferred fuel substrate, followed by glutamine and then glucose (median (95 per cent confidence interval) 567 (262-894), 63 (35-123) and 8.1 (5.1-18) pmol micrograms-1 h-1 respectively; P < 0.01, Mann-Whitney U test) in normal terminal ileal mucosa. The patients with ulcerative colitis had a significantly reduced rate of butyrate oxidation compared with the control group (194 (81-321) versus 567 (262-894) pmol micrograms-1 h-1, P < 0.05). Normal terminal ileal mucosa oxidized butyrate in greater quantities than glucose and glutamine. Ulcerative colitic terminal ileal mucosa exhibited an impaired rate of butyrate oxidation. PMID- 7881954 TI - Fate of the non-operated carotid artery after contralateral endarterectomy. AB - The long-term fate of the non-operated internal carotid artery (ICA) in 219 patients undergoing contralateral carotid endarterectomy was studied; 151 patients underwent serial postoperative imaging of the vessel. Cumulative freedom from stroke in the non-operated hemisphere was 99, 96 and 86 per cent at 1, 5 and 10 years respectively, giving a mean incidence of stroke of 1 per cent per annum. Only one stroke was preceded by a transient ischaemic attack and no stroke was associated with severe (70 per cent or greater) stenosis of the ICA. Ten patients (7 per cent) with initially mild or moderate disease of the non-operated ICA progressed to severe stenosis during follow-up, but only three became symptomatic and, in each case, the onset of symptoms preceded recognition of disease progression. The long-term risk of stroke in the non-operated ICA territory is very small. Of practical importance is that none of the observed strokes could have been prevented by postoperative surveillance of this type. PMID- 7881955 TI - Infective popliteal aneurysm following Salmonella bacteraemia. PMID- 7881956 TI - Predictive value of colour Doppler ultrasonography in detecting failure of vascular access grafts. AB - The predictive role of colour Doppler ultrasonography in determining the initial success and long-term patency of polytetrafluoroethylene (PTFE) vascular access grafts for haemodialysis was investigated. Two groups of patients were studied. The upper extremities of 21 patients in the control group were assessed by clinical examination only; those of 17 in a second group (Doppler group) were also assessed by ultrasonography before and after operation. Straight PTFE vascular access grafts were used between the brachial artery and axillary vein in all patients. The median preoperative brachial artery flow rate was significantly lower in patients who later developed graft thrombosis (66 versus 87 ml/min, P < 0.01), as was the median postoperative graft flow rate (480 versus 800 ml/min, P < 0.001). Routine preoperative and postoperative colour Doppler ultrasonography is recommended for every patient in whom a vascular access graft is planned. PMID- 7881957 TI - Effect of 'antiembolism' compression hosiery on leg blood volume. AB - Blood volume in the legs of healthy volunteers and the ability of graduated compression hosiery to reduce that volume were investigated with gamma scintigraphy. Changing posture from supine to upright, or pneumatic thigh cuffs inflated to either 20 or 40 mmHg with the subject supine, significantly increased leg blood volumes; the mean increase was: upright 126 ml, 20 mmHg cuff 44 ml, and 40 mmHg cuff 113 ml. A significant trend in reducing these volumes was noted in three brands of commercially available stockings, with the subject supine and without thigh cuffs (Page's L trend 132.5, P < 0.01) and when cuffs were applied at 20 mmHg (Page's L trend 128, P = 0.05). Few of the commercially available stockings delivered the 'standard' compression profile of 18 mmHg at the ankle, 14 mmHg at the calf and 8 mmHg at the upper thigh. The effects of other compression profiles were assessed, using custom-made stockings, and pneumatic cuffs inflated to 20 mmHg applied to the upper thighs to impede venous return. There was no consistent reduction of blood volume in the popliteal region, although decreases were seen in the upper and lower calf. The major determinant of performance was compression at the calf; the ankle to calf compression gradient was not important. Stockings with a profile of 16.8 mmHg at the ankle, 14.5 mmHg at the calf and 6.4 mmHg at the upper thigh performed best. PMID- 7881958 TI - Inflammatory mediators in acute pancreatitis. AB - The cellular events leading to acute pancreatitis are not well defined and the mechanism by which known aetiological factors initiate the disease process remains to be established. Inflammatory mediators have recently been implicated as potential early markers of disease severity and may help elucidate the pathophysiology of the disease. Oxidative stress is emerging as a common effector of the acinar cell injury in experimental acute pancreatitis and clinical findings indicate that neutrophil activation is a significant early event. In common with neutrophil-mediated tissue damage in states of tissue hypoperfusion, acute pancreatitis shows many features of an ischaemia-reperfusion injury. Increased levels of phospholipase A2 have been demonstrated; this enzyme induces synthesis of prostaglandins and platelet-activating factor, a potent inflammatory mediator. New therapeutic approaches to the complications of acute pancreatitis may be through manipulation of such mediators of inflammation. PMID- 7881959 TI - Recurrent varicose veins: a varicographic analysis leading to a new practical classification. AB - The varicograms of 128 legs were reviewed by a panel of two vascular surgeons and a radiologist with a specialist vascular interest. Varicography effectively elucidates the anatomical basis of recurrence. Recurrent varicose veins were associated with (i) technically unsatisfactory surgery at the saphenofemoral junction (66 per cent) and (ii) failure to remove the long saphenous vein in the thigh (60 per cent). A new classification is offered as a basis for comparison of series, audit and surgical training. PMID- 7881960 TI - Resection of paravertebral neurofibroma by video-assisted thoracoscopy. PMID- 7881961 TI - Effect of high-lipid high-nitrogen intravenous nutrition on total body nitrogen, visceral protein synthesis and nitrogen balance. AB - The impact of high-lipid intravenous nutrition (IVN) on selected indices of nitrogen retention following major surgical resection was studied. Twenty-two patients, randomly allocated to two equal well matched groups, received either high-lipid IVN (75 per cent non-protein calories supplied as lipid) or isocaloric isonitrogenous glucose IVN (100 per cent non-protein calories supplied as glucose). Total body nitrogen (assessed by in vivo neutron activation analysis), nitrogen balance and levels of circulating proteins were measured. Mean(s.d.) total body nitrogen and fat-free mass decreased (P = 0.04) in patients receiving high-lipid IVN, -109(36) gN and -1.7(0.4) kg respectively, but not in those given glucose-only IVN, 8(43) gN and 0.1(1.0) kg. This small loss of body protein does not appear to be clinically significant because postoperative hospital stay, complication rates and the acute-phase protein response (immunological and visceral) were similar in the two groups. PMID- 7881962 TI - Diagnostic difficulties in patients with a ruptured bladder. AB - Isolated bladder rupture has an insidious presentation which results in delayed diagnosis and management. Forty-four patients, of mean age 33.3 years, were seen over a period of 7 years. There was a history of trauma in 33 patients, although this was minor in 20. Alcohol intoxication, head injury or paraplegia could have led to lack of sensation of the distending and subsequently injured bladder in 18 patients. The mean delay between an identifiable incident or presentation and diagnosis was 5.4 days. The mean admission or preoperative levels of blood urea and creatinine were raised to 19.6 mmol/l and 362 mumol/l respectively in those with a delayed diagnosis. The diagnosis was made by voiding cystourethrography in 36 patients and by laparotomy in eight. When blood urea and creatinine concentrations are increased in a patient with an ill-defined abdominal ailment and a history of trauma or drunkenness, ruptured bladder should be considered. PMID- 7881963 TI - Ceiling-mounted radiographic equipment for trauma management in the emergency room. AB - Use of ceiling-mounted radiographic equipment in an emergency room for management of the multiply injured patient is described. The protocol of the Advanced Trauma and Life Support manual is followed and three plain radiographs (lateral cervical spine, anteroposterior views of the chest and pelvis) are obtained by the radiographers, who are members of the trauma team. Abnormalities were diagnosed on 7 per cent of the cervical radiographs, 31 per cent of the chest and 28 per cent of the pelvis in 108 patients during the first year of use. With full integration of the radiographers into the trauma team these three initial films are obtained within 10 min. Subsequent films can be taken of skeletal injuries found clinically or incidentally on the first three plain radiographs. It is recommended that all emergency rooms should have a ceiling-mounted radiographic unit with an automatic daylight processor to provide the best service for patients with major trauma. PMID- 7881964 TI - Management of alimentary tract duplication in children. AB - Duplication of the alimentary tract is rare but potentially dangerous. Five of 72 children with alimentary tract duplication treated between 1973 and 1992 died from postoperative complications; a further ten required more than one operation. Ileal duplications were the commonest, occurring in 16 patients (22 per cent). Thoracoabdominal duplications were the most complicated and responsible for much of the overall morbidity and mortality. Surgical complications were related to the size and location of the duplication, communication with the gastrointestinal tract or vertebral canal, presence of heterotopic gastric mucosa and involvement of mesenteric vessels. Complete excision of the duplication should be possible in most cases. PMID- 7881965 TI - Prospective randomized study of surgical morbidity following primary systemic therapy for breast cancer. AB - The influence of primary systemic therapy in treating operable breast cancer on postmastectomy morbidity rates was investigated. The contribution of other risk factors was assessed by multiple logistic regression. Seventy-nine eligible patients were randomly allocated, 39 to undergo immediate modified radical mastectomy, and 40 to receive initial cytotoxic or endocrine treatment followed by mastectomy. Postoperative wound seroma, infection and necrosis were recorded prospectively. Fourteen minor and six major complications occurred in 17 patients treated conventionally, while 14 patients developed 11 minor and six major complications after systemic therapy (P > 0.4). Median hospital stay was 8 days for both groups. Age, smoking, immediate breast reconstruction and the type of primary systemic treatment given were not independent predictors of complication risk. Obesity emerged as a significant risk factor for postmastectomy complications (P = 0.015). Primary systemic therapy does not increase the rate of morbidity after mastectomy. PMID- 7881966 TI - Scintigraphic detection of biliary fistula after removal of a T tube. PMID- 7881967 TI - Modulation of the cytokine and acute-phase response to major surgery by recombinant interleukin-2. AB - Major surgery suppresses host immune reactivity through alterations in monocyte and T cell-derived cytokine, eicosanoid and acute-phase protein release. Recombinant interleukin (IL) 2 augments T lymphocyte and monocyte activity in vitro. Eighteen patients, with localized colorectal cancer, were randomized to receive either recombinant IL-2 or placebo for 3 days by subcutaneous injection before surgery. Serum levels of IL-1 beta, IL-6, tumour necrosis factor alpha, soluble IL-2 receptor, C-reactive protein (CRP) and albumin were measured, and T lymphocyte surface expression of HLA-DR and CD25 and neutrophil phagocytosis were determined, before and for 21 days after surgery. Significant augmentation of IL 6, CRP and soluble IL-2 receptor production, enhanced expression of activation markers and increased neutrophil activity were found. Recombinant IL-2 may have a role in ameliorating the immunosuppression found after major surgery. PMID- 7881968 TI - Gastric motility following oesophagectomy. AB - The motility of the vagally denervated transposed stomach after oesophagectomy was examined by ambulatory gastric manometry and videofluoroscopy. Two groups of subjects were studied. Group 1 comprised ten patients who had undergone oesophagectomy 6-12 months previously and group 2 consisted of six normal control subjects. Studies were performed on fasting and fed subjects, and following injection of erythromycin 8 mg/kg. No distinguishable manometric wave activity was seen in either group while fasting. Feeding generated a measurable wave pattern in the patient group only. A significant increase in the mean (s.e.m.) distal wave amplitude was identified after infusion of erythromycin in both patients (34.0(15.1) versus 12.2(3.1) mmHg, P < 0.05) and controls (15.1(3.4) versus 5.0(0.0) mmHg, P = 0.05). The response to erythromycin was more rapid in patients than in controls (mean(s.e.m.) 113(16) versus 377(133) s, P < 0.05) and the effect persisted for longer (more than 1 h) in those who had undergone oesophagectomy. Videofluoroscopy confirmed purposeful motility in both the normal and vagally denervated stomach. It is concluded that the transposed stomach is a dynamic conduit. Enhancement of motility was greatest in the denervated stomach, indicative of denervation supersensitivity. PMID- 7881969 TI - Comparison of conventional Lewis-Tanner two-stage oesophagectomy with the synchronous two-team approach. AB - Twenty-seven patients with oesophageal carcinoma had subtotal oesophagectomy by the Lewis-Tanner operation (group 1, n = 14) or a synchronous modification (group 2, n = 13). Synchronous operations were completed more quickly (230 versus 305 min, P < 0.01), but with more time spent under single-lung anaesthesia (160 versus 120 min, P < 0.01) and a greater fall in systolic blood pressure during hiatal manipulation (60 versus 30 mmHg, P < 0.01). Operative blood loss was not significantly greater in group 2, but the total volume of blood transfused in the perioperative period was greater in this group (5 versus 3 units, P < 0.01). Four patients in group 1 suffered significant postoperative complications, compared with seven in group 2; three postoperative deaths occurred in group 2. This study suggests that the synchronous two-team oesophagectomy produces a higher incidence of complications than the conventional operation. Continued use of the Lewis Tanner two-stage oesophagectomy is recommended for patients with carcinoma of the oesophagus. PMID- 7881970 TI - Early oesophageal cancer: results of a European multicentre survey. Group Europeen pour l'Etude des Maladies de l'Oesophage. AB - Early oesophageal cancer has been extensively studied in Far-Eastern countries, where its prevalence is high. A multicentre survey was conducted within the Groupe Europeen pour l'Etude des Maladies de l'Oesophage to analyse results of surgical treatment in patients with disease staged as pTis-T1 N0 M0 according to the tumour node metastasis classification. Of 9743 patients with squamous cell oesophageal carcinoma observed since 1980, 4663 underwent resection; 253 (5.4 per cent) of these fulfilled the criteria for inclusion in the study. The overall mortality rate was 9.1 per cent (23 patients), and was higher after transthoracic than transhiatal oesophagectomy (10.7 versus 6 per cent, P not significant). Pathological examination showed an intraepithelial tumour in 46 patients (18.2 per cent), intramucosal carcinoma in 64 (25.3 per cent) and a submucosal lesion in 143 (56.5 per cent). The overall 5-year survival rate for patients with intraepithelial, intramucosal and submucosal tumours was 92.8, 72.8 and 44.3 per cent respectively. The 5-year survival rate was higher after transthoracic than transhiatal oesophagectomy (66 versus 52 per cent). No survival advantage was observed after either operation in patients with mucosal tumours. Of 21 patients with recurrent disease, 20 had a submucosal lesion. The 5-year survival rate in patients with submucosal tumour was higher after transthoracic than transhiatal oesophagectomy (54.2 versus 25.5 per cent). PMID- 7881971 TI - Signal transduction for taurocholic acid in the olfactory system of Atlantic salmon. AB - Conjugated bile acids such as taurocholic acid (TChA) are potent olfactory stimuli for Atlantic salmon (Salmo salar). A plasma membrane rich fraction was derived from salmon olfactory rosettes and used to investigate TChA signal transduction and receptor binding. In the presence of GTP gamma S, TChA caused dose-dependent stimulation of phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown, half maximal at less than 10(-7) M TChA. Stimulation of PIP2 breakdown by TChA required GTP gamma S, was blocked by GDP beta S, and was mimicked by A1F4 , consistent with a G protein requirement. A1F4- and Ca2+ stimulated breakdown of PIP2, but not phosphatidylcholine, arguing against a non-specific lipase activation. Stimulation of PIP2 breakdown by TChA was maximal at low Ca2+ concentration, < or = 10 nM. Conventional binding analysis with 3H-TChA was inconclusive due to a high degree of non-specific binding and to lack of tissue specificity expected for an olfactory receptor. Analysis of odorant amino acid binding indicated possible interaction of TChA with a putative acidic amino acid receptor but no interaction of TChA with a putative neutral amino acid receptor. We conclude that olfactory discrimination between amino acids and bile acids occurs in part at the receptor level while both classes of odors appear to use the same signal transduction mechanism, G protein mediated activation of phosphoinositide specific phospholipase C (PLC). PMID- 7881972 TI - Gustatory responsiveness of chorda tympani fibers in the cynomolgus monkey. AB - Responses of chorda tympani (CT) fibers of cynomolgus monkeys to various gustatory stimuli were analysed to obtain quantitative data on their response properties and to reveal the coding of gustatory information. Based on responses of 66 fibers to the four basic gustatory stimuli, they were classified into 16 sucrose-best, 28 NaCl-best, 11 HCl-best and 11 QHCl (quinine hydrochloride)-best fibers. Sucrose-best fibers were narrowly tuned to sucrose, while HCl-best fibers were broadly tuned to the four stimuli. The average breadth of response measure. H for all the 66 fibers was 0.375. The average value of H for sucrose-, NaCl-, HCl- and QHCl-best fibers was 0.276, 0.348, 0.634 and 0.384, respectively. Hierarchical cluster analysis performed on responses of 25 fibers to 14 gustatory stimuli revealed that all the stimuli except for 0.3 M Na-saccharin were grouped into four clusters; sucrose and 0.01 M Na-saccharin, NaCl and LiCl, acids, and non-sodium and -lithium salts, and QHCl. It is concluded that in the monkey CT each of the four classes of fibers predominantly contributes to mediate gustatory information for sweet, salty, sour and bitter stimuli. PMID- 7881973 TI - A quantitative study of dual action of nickel ions on the taste response to calcium ions of single fibers of the frog glossopharyngeal nerve: inhibition and enhancement by nickel ions. AB - Unitary discharges from single water fibers of the frog glossopharyngeal nerve, caused by stimulation with 0.02-5 mM CaSO4, were recorded from fungiform papillae with a suction electrode. NiSO4 at concentrations of 0.2-2 mM, namely, at concentrations that are barely effective in producing impulses, had a dual action on the Ca2+ response: NiSO4 caused both inhibition and enhancement of the Ca2+ response. In the present study, this dual action of Ni2+ ions on the Ca2+ response was investigated in detail. Single water fibers yielded a saturation type of concentration-response curve for CaSO4, which suggested that sulfate ions do not affect the Ca2+ response. Thus, sulfates were used as test salts in the present study. At low concentrations of Ca2+ ions, Ni2+ ions inhibited the Ca2+ response, but at higher concentrations of Ca2+ ions they enhanced it. The results can be explained quantitatively by the hypothesis that Ni2+ ions inhibit the Ca2+ response by competing with Ca2+ ions for the Ca2+ receptor (XCa) that is responsible for the Ca2+ response and that Ni2+ ions enhance the Ca2+ response by acting on a membrane element that interacts with XCa. Double-reciprocal plots of the data indicate that the enhancing action of Ni2+ ions is saturated at 1-2 mM Ni2+ ions and that Ni2+ ions at these concentrations increase the maximal response of the Ca2+ response by 182%. Dissociation constants for the Ca-XCa complex and the Ni-XCa complex were 4.2 x 10(-5) M and 7.6 x 10(-5) M, respectively. The analysis suggests that Ni2+ ions enhance the Ca2+ response by affecting the Ca-XCa complex without altering the affinity of XCa for Ca2+ ions. PMID- 7881975 TI - Dialysis and transplantation. PMID- 7881974 TI - A non-taste cue of sucrose in short-term taste tests in rats. AB - Data are presented showing that rats can discriminate among sucrose solution concentrations by some cue other than taste, possibly by olfaction. Non-taste factors need to be considered in taste discrimination studies. PMID- 7881976 TI - Diagnostics and techniques. PMID- 7881977 TI - The structural biology of glomerular epithelial cells in proteinuric diseases. PMID- 7881978 TI - New trends in immunosuppression for renal transplantation. PMID- 7881979 TI - The biology of allograft rejection. AB - Organ transplantation is the treatment of choice for patients with several end stage renal diseases. Despite improvements in immunosuppression and posttransplantation management of patients, allograft rejection remains a problem. In this review, we focus on the recent advances in molecular biology that have provided new opportunities to explore questions regarding the mechanisms of allograft rejection. We have concentrated on antigen presentation and the role of the direct and indirect pathway in allorecognition; effector mechanisms; adhesion molecules and lymphocyte homing; and the role of cytokines in regulating the different steps of rejection. PMID- 7881980 TI - HLA matching for improved cadaver kidney allocation. AB - Because long-term results of kidney transplantation are still unsatisfactory, efforts are needed to improve them, particularly through the allocation of well matched kidneys to recipients. In the past 7 years, the United Network of Organ Sharing 6-antigen match program has established that superior results can be obtained with the national sharing of available no HLA-A, -B, or -DR antigen mismatched kidneys. In addition to strengthening this program, the 1 HLA-A, -B, or -DR antigen-permissible mismatched kidneys should also be shared nationally. Approximately half of the recipients would receive nationally matched kidneys and the remaining recipients would be allotted kidneys locally, with distribution based on fewer risk factors (eg, residues) and on waiting points. This residue matching method was shown to result in more equitable kidney distribution to minorities. PMID- 7881981 TI - Chimerism after whole organ transplantation: its relationship to graft rejection and tolerance induction. AB - Bone marrow-derived "passenger" leukocytes that normally reside in the interstitial tissues of whole organs migrate into the recipient after transplantation and establish microchimerism. An equally important phenomenon is the reciprocal migration of circulating recipient leukocytes, which repopulate the interstitium of whole organ allografts. This bidirectional exchange and interaction of bone marrow-derived cells after organ transplantation is considered a seminal event in the acceptance of allografts and in the induction of donor-specific tolerance. The apparent dichotomous role of donor cell chimerism in the processes of organ rejection and acceptance is discussed. PMID- 7881982 TI - New biologic immunosuppressive agents in transplantation. AB - Antigen-specific immunologic nonresponsiveness (tolerance) to alloantigens is a goal in transplantation. Most successful strategies of tolerance induction target the T cell. Activation of a quiescent T cell requires two different signals. Signal 1 is delivered when the T-cell receptor is engaged by foreign antigen presented by major histocompatibility complex molecules. Several potential pathways exist to deliver signal 2, which is also termed a costimulatory signal, although by far the best characterized pathway is through the T-cell co-receptor CD28. Blockade of either signal 1 or signal 2 may be sufficient to induce tolerance to alloantigens. Recent advances in knowledge of T-cell receptor-major histocompatibility complex interactions, in mechanisms of self-tolerance and in the identity and importance of costimulatory receptors and their ligands, have led to the development of various new strategies to block signals 1 and 2 using biologic agents. This review focuses on the most promising new modalities. PMID- 7881983 TI - Recurrent renal disease after renal transplantation. AB - Recurrent disease does not lead to the loss of large numbers of allografted kidneys, but it is a source of serious concern in recipients with type I hyperoxaluria and focal segmental glomerulosclerosis. In patients with a number of other causes of renal failure, it may affect the use of living related donors. Recent topics for debate include the failure of cyclosporine to modify the incidence of recurrent disease, the realization that IgA nephropathy may in the long term lead to graft destruction, the fact that membranous nephropathy may recur in a quarter of the cases, and the knowledge that a nephrotic syndrome may reappear after transplantation for the Finnish congenital nephrotic syndrome. PMID- 7881984 TI - Risk factors for cardiac morbidity and mortality in dialysis patients. AB - Clinical and echocardiographic manifestations of cardiac disease are frequently present in patients starting end-stage renal disease therapy. Congestive heart failure, ischemic heart disease, systolic dysfunction, concentric left ventricular hypertrophy, and left ventricular dilatation are significant, adverse prognostic indicators, independent of age, diabetes mellitus, and smoking. Risk factors related to the uremic state, which are potentially reversible, include inadequate dialysis, anemia, hypoalbuminemia and hypocalcemia. Hypertension predisposes patients to congestive heart failure, following the development of which hypotension becomes an independent predictor of mortality. PMID- 7881985 TI - Calcitriol pulse therapy in patients with end-stage renal failure. AB - To maximize the effects of calcitriol on parathyroid glands and bone without inducing frequent episodes of hypercalcemia, two new therapeutic approaches, intravenous therapy and intermittent pulse oral administration, have been advocated. To date, detailed results of 23 studies have been reported. All clinical trials were prospective; however, none included a placebo-control group, and only one study reported on bone histology. Review of these data indicates that in principle, both intravenous and pulse oral therapy are equally efficient in decreasing serum parathyroid hormone levels. However, both approaches induce relatively frequent episodes of hypercalcemia and, to a lesser degree, hyperphosphatemia, necessitating close monitoring during therapy. In addition, a subset of patients did not respond to either therapy without clearcut characteristics that would allow them to be identified before the start of therapy. More controlled studies that include bone histology are needed to elucidate this question. At this time, it appears that patients with severe predominant hyperparathyroidism can benefit from intravenous or pulse oral therapy, which may allow them to avoid parathyroidectomy. However, further studies are needed in patients with mild to moderate secondary hyperparathyroidism to determine whether intermittent therapies are superior to daily oral therapy in preventing parathyroid gland hyperplasia and renal bone disease. PMID- 7881986 TI - Monitoring of iron status and iron supplementation in patients treated with erythropoietin. AB - Patients receiving erythropoietin therapy require large quantities of iron to keep pace with the demands of the bone marrow during active erythropoiesis. If this iron supply to the marrow is not maintained, the response to erythropoietin is impaired, and indeed iron insufficiency is the most common cause of a poor response to this drug. Iron deficiency may be either absolute, which is defined as a reduction in total body iron stores, or functional, which implies adequate iron stores but a failure to supply available iron to the marrow or a failure in the utilization of this iron in the process of erythropoiesis. The detection of absolute or functional iron deficiency is difficult because there is no absolutely reliable marker of iron status, with the exception of an unequivocally low serum ferritin level. Measurement of serum ferritin and transferrin saturation are the most widely used methods, but both have drawbacks. Monitoring of the percentage of hypochromic erythrocytes in the circulation also seems promising, but the technology is of limited availability, and other methods (eg, monitoring erythrocyte ferritin, free erythrocyte protoporphyrin, and erythrocyte zinc protoporphyrin levels) lack widespread validation. Treatment of iron insufficiency is accomplished by intensifying iron supplementation either orally or intravenously, and in many instances the latter route becomes necessary. The high cost of erythropoietin demands that iron deficiency be screened for on a regular basis and treated to maximize the benefits of this drug. PMID- 7881987 TI - Diagnostics and techniques. PMID- 7881988 TI - Current concepts in the diagnosis of urinary tract infection. PMID- 7881989 TI - Pathogenesis and measurement of insulin resistance in hypertension. AB - Because of its association with a constellation of cardiovascular risk factors, insulin resistance has recently emerged as a major clinical disorder. There is therefore an increasing need to accurately assess insulin sensitivity in clinical and epidemiologic studies. The merits of various techniques for measuring insulin action are briefly reviewed. Essential hypertension and insulin resistance appear to be tightly linked; however, the mechanism or mechanisms accounting for this association are not known. Central or intra-abdominal obesity is a particularly strong risk factor for the development of hypertension. The weight of the evidence suggests that hyperinsulinemia per se is not a potent instrumental factor in the development of hypertension. Mechanisms suggesting that insulin resistance independent of hyperinsulinemia may predispose to increased vascular tone are discussed. Conversely, the possibility that essential hypertension could engender insulin resistance is proposed. The link between insulin resistance and hypertension is likely to be complex and multifactorial. PMID- 7881990 TI - Direct measurement of sympathetic activity: new insights into disordered blood pressure regulation in chronic renal failure. AB - The ability to record sympathetic nerve activity in conscious human subjects using intraneural microelectrodes (microneurography) has proven to be a powerful clinical research tool, which has shed new light on the pathophysiology of important blood pressure problems as exemplified in studies of patients with chronic renal failure. Hypertension is present in the majority of hemodialysis patients and is a major risk factor for their excessive mortality from heart attack and stroke. Microneurographic studies indicate that there is a neurogenic component to this hypertension. In addition, severe episodic hypotension is an important complication of maintenance hemodialysis. Microneurographic studies have advanced the concept that abrupt paradoxical withdrawal of sympathetic vasoconstrictor drive is an important cause of this episodic hypotension. These microneurographic data provide the conceptual framework for systematic assessment of new therapeutic strategies. PMID- 7881991 TI - Ultrasonic techniques for the evaluation of hypertension. AB - Echocardiography and arterial ultrasound provide "windows" through which the structure and function of the heart and arterial tree can be evaluated noninvasively. M-mode, two-dimensional, and Doppler echocardiographic techniques have been well validated and can measure left ventricular (LV) mass, define LV geometric patterns, and assess systolic and diastolic LV performances. Numerous long-term studies document that echocardiographic detection of LV hypertrophy or concentric remodeling identifies patients with hypertension at a two- to fourfold increased risk of myocardial infarction, stroke, or death. Similarly, well validated ultrasonic methods can measure the lumen size, wall thickness, presence of atheroma, and aspects of function of the carotid artery and other systemic arteries. Increased arterial wall thickness and discrete atherosclerotic plaques also identify individuals at high risk. Meticulous attention to echocardiographic technique is needed to derive the full benefit for patient management of noninvasive characterization of the heart. PMID- 7881992 TI - Criteria for the diagnosis of urinary tract infection. AB - Despite years of clinical experience with urinary tract infection, the criteria for the diagnosis of this common condition are controversial. Accumulating evidence confirms prior suggestions that criteria must be flexible and varied, depending on the clinical syndrome encountered. The combination of pyuria and bacteriuria, with a uropathogen present at a urine colony count level predictive of infection, offers the best way to distinguish infection from contamination of the collected urine specimen. The level of bacteriuria on quantitative urine culture that should be considered significant varies from 10(2) to 10(5) colonies or more per milliliter of urine, depending on the clinical setting. PMID- 7881993 TI - The significance of urine culture with mixed flora. AB - Urine cultures that contain more than one organism are usually considered contaminated. The frequency with which such growth truly represents mixed infection is unknown. Surprisingly few studies have evaluated the clinical significance of polymicrobial growth from urine. Such significance was demonstrated in these studies either by recovering the same combination of microorganisms from blood and urine, in cases of urosepsis, or by the reproducibility of the same mixture of bacteria from sequential urine cultures. In certain clinical settings, polymicrobial bacteriuria is not only frequently significant but its overall clinical impact seems to be substantial. Bacteriuria associated with long-term catheterization, the most common nosocomial infection in American medical care facilities, is predominantly polymicrobial. Symptomatic urinary tract infection is a common outcome of such bacteriuria and has been associated with increased risk for bloodstream infections and excess mortality. Early species identification and antimicrobial susceptibility testing of each urinary isolate may be of paramount benefit to the care of these patients. We believe that in properly collected urine samples, multiple growth often represents true mixed infection and should therefore be completely evaluated. PMID- 7881994 TI - Imaging techniques in the diagnosis of urinary tract infection. AB - In terms of future morbidity and mortality, one of the most important considerations in urinary tract infection is the age of the patient. In adults, only those with complications or illnesses that fail to respond to treatment require investigation to exclude underlying pathology. In contrast, the young are at risk of future hypertensive and renal disease; imaging techniques are therefore of paramount importance to identify those with renal parenchymal disease at an early stage and permit appropriate and adequate treatment. 99mTc dimercaptosuccinic acid scintigraphy is emerging as the method of choice for this purpose, because it combines high specificity and sensitivity with convenience, repeatability, and acceptable radiation doses. Voiding cystourethrography will also be required in many cases to exclude bladder pathology. New developments include the use of color Doppler ultrasonography and the nuclear magnetic resonance technique of rapid acquisition recall echo urography, both of which may become of value for the detection of scarring. PMID- 7881995 TI - Function and evolution of superficial neuromasts in an Antarctic notothenioid fish. AB - Extracellular recording techniques were used to measure frequency response functions of anterior and posterior lateral line nerve fibers innervating superficial neuromasts at five different locations on the head and trunk of an antarctic notothenioid fish, Trematomus bernacchii. Scanning electron microscopy was used to measure neuromast size according to location. Fibers innervating neuromasts from all locations were similar in showing equal responsiveness in the 10-30 Hz range to equal pk-pk velocity levels of a sinusoidally vibrating sphere. The mean cut-off frequency (CF) at which responsiveness declined to 50% of maximum was 46 Hz for all fibers combined. Superficial neuromasts located on the ventral trunk line were three to six times larger in surface area than most other neuromasts. The mean CF for fibers innervating these large neuromasts was 7-18 Hz lower than mean CF's corresponding to other superficial neuromast locations, but small differences in mean CF's were not consistently related to neuromast size. It is argued that fiber responses from different superficial neuromasts are more similar than dissimilar and that the evolution of large superficial neuromasts on the ventral trunk line is linked to a general paedomorphic trend among notothenioid fishes that may be essentially non-adaptive for the lateral line. PMID- 7881996 TI - Form and function relationships in lateral line systems: comparative data from six species of Antarctic notothenioid fish. AB - The structure and physiology of the anterior lateral line canal systems were studied in six species of fish belonging to two different families within the suborder of antarctic fish Notothenioidei. Many of the canals within the species belonging to the genus Trematomus are relatively straight sided tubes with diameters around 0.4 mm. Some of the canals in Trematomus, and most of the canals in the icefishes (family Channichthyidae) are more complex. Relatively small pores lead into large tubules, the walls of which appear partially membranous, and the canals not much more than constrictions between adjacent tubules. Dissostichus mawsoni, a large species, has canals with distinctive wide and narrow sections, 1.8 mm and 0.48 mm, respectively. Despite these morphological differences the frequency response characteristics of anterior lateral line units are remarkably similar in all six species. In the case of D. mawsoni, this functional similarity results from narrow sections of the canals, which provide the viscous resistance to flow that preserves the mechanical filtering properties of the canal despite the huge size difference between D. mawsoni and the other species. It is argued that the most appropriate way to view canals is as high pass filters which attenuate lower frequencies, and that this effect is best illustrated by comparing the frequency response characteristics of superficial and canal neuromasts using a sinusoidal stimulus that has a constant peak-to-peak velocity. The functional contribution of canals is to attenuate low frequencies and improve the signal-to-noise ratio for biologically important signals in the presence of low frequency noise produced, for example, by the animal's own movements. PMID- 7881997 TI - The retinal ganglion cell layer and optic nerve in a marsupial, the honey possum (Tarsipes rostratus). AB - We examined the retina and optic nerve of one of the smallest mammals, the honey possum (Tarsipes rostratus), a marsupial. Ganglion and displaced amacrine cells were distinguished by morphological criteria in retinal wholemounts stained with cresyl violet. There was a mean of 90,000 ganglion cells which were distributed as an area centralis in the mid-temporal retina with a peak density of 9,000/1 mm2 falling in a concentric shallow gradient to 2,000/1 mm2 at the periphery. The unimodal and positively skewed spectra of soma diameters gave no indication of ganglion cell classes. Displaced amacrine cells numbered only 15,000, being outnumbered 6:1 by ganglion cells. This value represents by far the lowest percentage of displaced amacrine cells yet reported for a mammalian retina. The displaced amacrine population was evenly distributed. Counts of optic axons from electron micrographs were within 1-5% of the ganglion cell estimates. In the retrobulbar portion of the nerve, a substantial proportion of axons (26-43%) were unmyelinated, and many of these were concentrated within the lateral quadrant. This specialisation may represent the outflow of the area centralis. At the level of the foramen, the percentage of unmyelinated axons fell to 4-6%, and axons were more uniform in their distribution. Axon diameters were lower for the unmyelinated than the myelinated populations at both levels. As for ganglion cells, however, the spectra of axon diameters were unimodal and positively skewed for both unmyelinated and myelinated axons. PMID- 7881998 TI - Brain morphogenesis of the red sea bream, Pagrus major (teleostei). AB - Post-embryonic morphogenesis and regional volumetric growth of the brain in larval and juvenile red sea bream, Pagrus major, were analyzed by employing a computer-aided three-dimensional reconstruction of serial sections of the head. The relative volume of the optic tectum rapidly increases after hatching until day 8, implying the importance of the visual sense for the first feeding, which begins on day 4. The differentiation and outgrowth of the primary gustatory center in the medulla after day 43 may reflect the increasing number of taste buds, suggesting a relationship to the onset of benthic feeding as juveniles. The rather rapid increases in the relative volumes of the corpus and valvula cerebelli after day 28 and their progressive morphogenesis may be correlated with improved motor performance. The relative volumes of the octaval-lateral line centers, including the eminentia granularis and the crista cerebellaris, and the relative volume of the torus longitudinalis, increase in parallel with those of the corpus and valvula cerebelli. PMID- 7881999 TI - Descending telencephalic information reaches longitudinal torus and cerebellum via the dorsal preglomerular nucleus in the teleost fish, Pantodon buchholzi: a case of neural preaptation? AB - The weakly electric mormyrids are known to have an ascending neuronal pathway that reaches the diencephalon and carries information concerned with electrolocation. The recipient diencephalic center, the dorsal preglomerular nucleus, receives a massive telencephalic input and projects to the corpus and valvula cerebelli. This circuitry has been interpreted as a uniquely derived (autapomorphic) feature for mormyrids. In the present study, we demonstrate with the fluorescent neuronal tracer DiI that the closely related, but non electroreceptive, teleost Pantodon buchholzi possesses a dorsal preglomerular nucleus with similar telencephalo-cerebellar circuitry. The projection to the cerebellum only reaches the corpus, however, not the valvula cerebelli. Further, the dorsal preglomerular nucleus of Pantodon displays a descending pathway via the torus longitudinalis. Two phylogenetic interpretations for the presence of telencephalo-cerebellar pathways in both mormyrids and Pantodon are possible: if such a pathway existed as a preaptation in the common ancestor of mormyrids and Pantodon, it must be an exaptation for electroreception in mormyrids, since this sensory modality evolved anew in this teleost group; alternatively, the pathway evolved in parallel homoplasy, once in Pantodon, as part of a descending premotor pathway, and independently in mormyrids, where the system gains access to ascending electrosensory information. PMID- 7882000 TI - Chloride-dependent pH regulation in connective glial cells of the leech nervous system. AB - We used double-barreled pH-sensitive microelectrodes to study the mechanisms by which the intracellular pH is regulated in the connective glial cells of the medicinal leech. The experiments indicate that a Cl(-)- and HCO3(-)-dependent mechanism mediates some recovery from intracellular alkalosis even in the absence of external Na+. This suggests the presence of Na(+)-independent Cl-/HCO3- exchange in the connective glial membrane. At alkaline pHi, this exchange most likely operates in the direction of net acid loading (i.e. HCO3- efflux). PMID- 7882001 TI - Hippocalcin expression in the brain of the Snell dwarf mutant mouse. AB - To determine factors contributing to the expression of the brain-derived protein, hippocalcin, we mapped its distribution in the brain of Snell pituitary dwarf mutant mice (dw) by immunohistochemical and immunoblot methods. Our findings are as follows. (1) In the hippocampus, hippocalcin immunoreactivity was found in the cell body and dendrites of pyramidal neurons of the normal controls and dw mice, although the intensity of immunoreactivity in the dw mice was lower. (2) In the cerebellum, hippocalcin immunoreactivity was strongly expressed in the Purkinje cell body of both the control and dw mice. However, the Purkinje cell dendrites were found to be more intensely stained in the dw mice than in the normal controls. (3) In the dw cerebral cortex, the pyramidal neurons of layers II to VI strongly expressed hippocalcin, whereas its expression in the controls was weak. (4) The amount of hippocalcin in the dw hippocampus was less than in the normal controls, whereas the amount in the dw cerebral cortex and cerebellum was greater. These results indicate that the developmental expression of hippocalcin in the dw brain is affected by the retarded maturation of the neuronal network due to the deficient hormonal state (the lack of growth and thyroid hormones). PMID- 7882002 TI - Effects of subchronic pretreatment with D-fenfluramine or p-chloroamphetamine on [3H]inositolmonophosphate accumulation in rat cortical miniprisms. AB - Phosphatidylinositol (PI) breakdown in rat cerebral cortex is stimulated by serotonin (5-HT), acting via 5-HT2 and possibly 5-HT3 receptors and by acetylcholine or carbachol, acting via muscarinic M1 and M3 receptors. Serotoninergic neurons have been described as tonically inhibiting cortical acetylcholine release. We studied the effects of subchronic pretreatment with high doses of D-fenfluramine (10 mg/kg, i.p., daily for 4 days), which releases 5 HT and blocks its reuptake, on 5-HT-and carbachol-stimulated PI breakdown, as measured by [3H]inositolmonophosphate ([3H]IP1) accumulation in cortical miniprisms. This pretreatment decreased 5-HT-stimulated [3H]IP1 accumulation, suggesting that a prolonged increase of 5-HT in the synaptic cleft reduces the activity of the transducing system used by postsynaptic 5-HT receptors. Carbachol stimulated PI breakdown was unaltered by pretreatment with D-fenfluramine. Pretreatment with a single dose of p-chloroamphetamine (5 mg/kg), a serotoninergic neurotoxin, which depleted cortical 5-HT by 85%, did not change [3H]IP1 accumulation after stimulation by 5-HT or by the muscarinic agonist carbachol. Subchronic pretreatment, which depleted cortical 5-HT by 90%, decreased both 5-HT- and carbachol-stimulated [3H]IP1 accumulation. The mechanism by which p-chloroamphetamine, but not D-fenfluramine, diminishes the PI response to carbachol might involve impairment of the tonic serotoninergic inhibition of acetylcholine release. PMID- 7882003 TI - Ontogeny of protein kinase C in the rat hippocampus: an autoradiographic study with [3H]phorbol 12,13-dibutyrate. AB - The ontogeny of protein kinase C (PKC) in the hippocampus was studied in 1-week-, 4-week-, and 3-month-old Wistar rats with in vitro receptor autoradiography using [3H]phorbol 12,13-dibutyrate ([3H]PDBu). The developmental pattern of [3H]PDBu binding varied within hippocampal subregions. [3H]PDBu binding in stratum oriens of the CA1 and CA3 sectors and stratum lucidum of the CA3 sector increased to adult levels by 4 weeks. In strata moleculare and granulosum of the dentate gyrus, the binding reached peak values at 4 weeks but declined at 3 months. Interestingly, in stratum lacunosum-moleculare of the CA1 sector, the [3H]PDBu binding activity was the highest at 1 week. There were constant binding activities in stratum radiatum of the CA1 and CA3 sectors and the dentate hilus during the postnatal development. These findings may provide evidence that PKC has a distinct role in different subregions of the hippocampus during postnatal development. PMID- 7882004 TI - Hypothalamic cholinergic and noradrenergic neurons in hyperglycemia induced by 2 deoxyglucose. AB - To investigate the contribution of the hypothalamic cholinergic and noradrenergic neurons in 2-deoxyglucose (2-DG) induced hyperglycemia, we after microwave irradiation analyzed the contents of the neurotransmitters and the metabolites in the microdissected hypothalamic nucleus, ventromedial hypothalamic nucleus (VMH), paraventricular nucleus (PVN) and lateral hypothalamus (LH). A dose dependent decrease in the acetylcholine (ACh) content and a corresponding increase in the choline content was observed in those hypothalamic nuclei 20 min after intravenous administration of 250 or 500 mg/kg 2-DG. The norepinephrine content decreased in 500 mg/kg 2-DG group but did not change significantly in the 250 mg/kg group. These results suggest the involvement and importance of the hypothalamic cholinergic system in 2-DG induced hyperglycemia and, furthermore, that the hyperglycemic response can not be solely attributed to the noradrenergic system. PMID- 7882005 TI - Release of alpha-neoendorphin from the anterior pituitary gland of conscious rats. AB - alpha-Neoendorphin (alpha-NEO) is a proenkephalin B-derived opioid peptide and kappa type opioid receptor agonist. In the present study, we used a combination of microdialysis and a highly sensitive radioimmunoassay to measure the extracellular levels of immunoreactive (ir)-alpha-NEO from the anterior pituitary gland of conscious free-moving rats. When rats were given water ad libitum under a 12:12 h light-dark cycle with lighting from 06.00 to 18.00 h, ir-alpha-NEO showed circadian rhythmicity that peaked at 00.00-03.00 h and reached a minimum at 12.00-15.00 h. Furthermore, we investigated whether naloxone (10(-6) to 10(-8) M) affected ir-alpha-NEO level. The alpha-NEO release induced by naloxone was optimum at 10(-7) M, and 10(-6) M naloxone seemed to induce alpha-NEO release to a lesser degree. These results suggested that alpha-NEO release by naloxone might be mediated via anterior pituitary cell auto-receptor (kappa type) inhibition. PMID- 7882006 TI - NMDA receptor-mediated expression of Fos protein in the rat striatum following methamphetamine administration: relation to behavioral sensitization. AB - In order to clarify the possible involvement of N-methyl-D-aspartate (NMDA) receptors in mediating striatal Fos protein induction and behavioral sensitization after methamphetamine administration, we examined the effects of non-competitive NMDA receptor antagonist MK-801 on these phenomena in rats. A single administration of 1.0 and 5.0 mg/kg methamphetamine resulted in a dose dependent increase in Fos-immunoreactive cells in the medial striatum. Prior exposure to 5.0 mg/kg methamphetamine enhanced ipsilateral rotational behavior in response to subsequent methamphetamine administration in unilateral nigral lesioned rats (sensitization). Pretreatment with 1.0 mg/kg MK-801 completely prevented both the expression of striatal Fos protein and the development of acute behavioral sensitization following a single injection of 5.0 mg/kg methamphetamine. These results suggest that NMDA receptor-mediated mechanisms contribute to the expression of striatal Fos protein associated with behavioral sensitization that follows exposure to methamphetamine. PMID- 7882007 TI - Maturation and segregation of brain networks that modify seizures. AB - The mature brain is less susceptible to seizures than the immature brain. We demonstrate that in the mature substantia nigra (SN) there are two topographically discrete GABAA-sensitive regions which differ in the amount of mRNA expression of the GABAA receptor alpha 1 subunit. These two regions mediate separate anticonvulsant and proconvulsant effects and use divergent projection networks. By contrast, in the immature SN there is no special topography of mRNA expression of the alpha 1 subunit and only the proconvulsant network is present. The decreased seizure susceptibility of the mature brain may be related to postnatal segregation of GABAA-sensitive networks. PMID- 7882008 TI - Facilitatory effect of olfactory bulbectomy on 2-deoxyglucose uptake in rat amygdala slices. AB - The aim of the present study was to determine whether the 2-deoxyglucose uptake of amygdala slices was affected by olfactory bulbectomy. At 7, 14 and 21 days post-lesion, bilateral olfactory bulbectomized rats exhibited a significant increase of 2-deoxyglucose uptake in amygdala slices, but not in the cerebral cortex. In addition, unilateral olfactory bulbectomized rats showed a high uptake of 2-deoxyglucose uptake in the ipsilateral amygdala, but not in the contralateral amygdala. These results suggest that the enhancement of 2 deoxyglucose uptake is related to the hyperexcitability of amygdala neurons following bulbectomy, and that this enhancement may be responsible for the behavioral changes in olfactory bulbectomized rats. PMID- 7882009 TI - Involvement of D1 dopamine receptor mechanism in ischemia-induced impairment of CA1 presynaptic fiber spikes in rat hippocampal slices. AB - The effect of dopamine (DA) receptor agonists and antagonists on hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 presynaptic fiber spikes elicited by the stimulation of Schaffer collateral were investigated using hippocampal slices. Treatment with D1 dopamine receptor antagonist, SCH23390 produced a concentration-dependent attenuation of the ischemia-induced decrease of presynaptic potentials. The magnitude of recovery of the CA1 presynaptic potential in SCH233390-treated slices at 10 and 100 microM was 28 and 54%, respectively. Whereas, treatment with D1 dopamine receptor agonist, SKF38393 exacerbated the ischemia-induced decrease in the CA1 presynaptic potential. The decrease of CA1 presynaptic potential by ischemia was affected by neither D2 dopamine receptor agonist, bromocriptin and quinpirole nor D2 dopamine receptor antagonist, sulpiride. The neuroprotective effect of SCH23390 was completely blocked by cotreatment with SKF38393. The present results demonstrated that the blockade of D1 dopamine receptor function played a neuroprotective role in ischemic damage, suggesting a facilitatory role of D1 dopamine receptor-operated function in ischemia-induced neuronal deficits. PMID- 7882010 TI - Basic fibroblast growth factor increases cortical blood flow in vivo. AB - Basic FGF has recently been shown to produce systemic and cerebral vasodilation. To test the hypothesis that bFGF increases regional cortical blood flow (rCBF), rCBF and brain pHi were measured while bFGF or vehicle was superperfused onto the cortex of rabbits. The results of this study demonstrate that topical application of bFGF causes an increase in rCBF. PMID- 7882011 TI - Long-term depression requiring tACPD-receptor activation and NMDA-receptor blockade. AB - In slices from the rat visual cortex, application of the metabotropic glutamate receptor (mGluR) agonist trans-1-aminocyclo-pentane-1,3-dicarboxylic acid (tACPD), whether combined with tetanization or not, produced only a reversible depression but not long-term depression (LTD) of synaptic transmission. In the presence of both tACPD and the NMDA receptor antagonist D-(-)-2-amino-5 phosphonopentanoate, tetanization induced LTD. These findings suggest requirement of tACPD-sensitive mGluR subtypes for inducing a form of LTD in the visual cortex. PMID- 7882012 TI - Transection of corticostriatal afferents abolishes the hyperexpression of Fos and counteracts the development of rotational overcompensation induced by intrastriatal dopamine-rich grafts when challenged with amphetamine. AB - The present study was carried out to test whether the abnormally high striatal Fos activation induced by amphetamine and the overcompensation of amphetamine induced rotation in 6-hydroxydopamine-lesioned rats receiving transplants of fetal nigral neurons can be reduced by a lesion of the corticostriatal projection. Fetal ventral mesencephalic tissue was transplanted as a cell suspension into the dopamine-denervated striatum of unilaterally 6 hydroxydopamine-lesioned rats. Rats in which the transplants had produced a complete compensation or reversal of the lesion-induced rotational asymmetry in response to amphetamine (5 mg/kg, i.p.) were divided into two equal groups, sustaining either a knife-cut transection of prefrontal corticofugal efferents ipsilaterally to the grafts, or a sham-lesion. The animals were re-tested for amphetamine-induced rotation one week post-operatively, and were perfusion-fixed two hours after drug administration. Adjacent sections through the striatum were processed for Fos and tyrosine hydroxylase immunohistochemistry. At the amphetamine rotation test performed after cortical lesion surgery, the frontocortically deafferented animals exhibited a low rate of rotation in the direction ipsilateral to the dopaminergically denervated and grafted side, while sham-lesioned rats rotated towards the intact side. In sham-lesioned controls, the density of Fos-immunoreactive nuclei (no. of nuclei/mm2) was significantly higher in the reinnervated portion of the grafted striatum than on the contralateral side (+54 to 316%). In the frontocortically deafferented-grafted striata, Fos expression was not different from that measured on the contralateral side and significantly lower than in the sham-lesioned controls (-65 79%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882013 TI - Evidence that angiotensin-(1-7) plays a role in the central control of blood pressure at the ventro-lateral medulla acting through specific receptors. AB - In this study we determined which angiotensin receptors may mediate the cardiovascular effects elicited by angiotensin-(1-7) [Ang-(1-7)] in the rostral ventrolateral medulla (RVLM) and caudal pressor area (CPA) of the ventrolateral medulla (VLM) of anesthetized rats. Furthermore the role of endogenous angiotensins in these areas was also investigated. The pressor effect produced by unilateral microinjection of Ang-(1-7) into the RVLM or CPA was not modified by either the AT1 receptor antagonist, DuP 753 or by the AT2 receptor antagonist, CGP 42112A, but was completely blocked by the Ang-(1-7) selective antagonist, A 779. In contrast, the pressor effect produced by microinjection of angiotensin II (Ang II) was completely blocked by DuP 753 but was not changed by CGP 42112A or A 779. Bilateral microinjection of A-779 into the RVLM or CPA produced a significant fall in mean arterial pressure and heart rate. Microinjection of DuP 753 produced a pressor effect comparable to bilateral injection of vehicle. These results indicate that, although Ang II acts in the VLM through an AT1 receptor subtype, the cardiovascular effects produced by microinjection of Ang-(1-7) into the RVLM and CPA are mediated by a specific angiotensin receptor (AT5?). Furthermore, our data provide evidence that endogenous Ang-(1-7) participates at the VLM in the neural control of arterial blood pressure. PMID- 7882014 TI - Electrophysiology and morphology of neurons in rat perirhinal cortex. AB - The intrinsic membrane properties of perirhinal cortical neurons were studied by intracellular recording in in vitro rat brain slices. Gross morphology was also examined through injection of the fluorescent dye carboxyfluorescein. The cells encountered displayed a diversity of electrophysiological properties, and were similar to cells reported in other neocortical areas with regard to spiking patterns, afterpotentials, and morphology. However, very few (4%) intrinsically bursting neurons were encountered. Two pyramidal cells with thick apical dendrites were filled, and both fired doublets of action potentials for their first suprathreshold events. Of the filled pyramidal cells with thin apical dendrites, most (9/11) fired single action potentials for their first suprathreshold events. A variety of classification schemes were used to group the data, and several schemes were found to be equally successful. According to one of the schemes, cells recorded with carboxyfluorescein filled electrodes had significantly greater action potential widths at half-amplitude and more depolarized resting potentials than cells recorded without this dye. PMID- 7882015 TI - Pharmacological characterization of the rat cerebellar endothelin B (ETB) receptor using the novel agonist radioligand [125I]BQ3020. AB - A novel linear peptide fragment of endothelin-1 (ET-1), N-acetyl-[Ala11,15]ET-1[6 21] (BQ3020) has been identified as a potent and ETB-selective agonist. The present studies were conducted in order to characterize the binding of [125I]BQ3020 to the ETB receptor in rat cerebellum. [125I]BQ3020 (0.1 nM) bound with high specificity (90% of total binding) and selectivity for the ETB receptor. ET-1, ET-2, and ET-3 inhibited 0.1 nM [125I]BQ3020 binding with equivalent affinity (Ki values = 55-110 pM). The sarafotoxins S6a, S6b, and S6c also potently inhibited [125I]BQ3020 binding (Ki values = 55-2000 pM). The ETA selective antagonist, BQ123 (100 microM) did not significantly inhibit [125I]BQ3020 binding. Ligand saturation studies indicated that [125I]BQ3020 labeled a single class of recognition sites with very high affinity (Kd = 31 pM) and limited capacity (Bmax = 570 fmol/mg protein). High affinity 0.1 nM [125I]BQ3020 binding was reduced by 40-50% in the presence of 1 mM guanine nucleotides. Additional competition studies indicated that ET-1 and ET-2 produced biphasic inhibition curves in competing for 0.5 nM [125I]BQ3020. The high affinity component of the ET-1 inhibition curve was subsequently eliminated in the presence of 1 mM GTP-gamma-S The guanine nucleotide sensitivity of [125I]BQ3020 binding offers the possibility that different functional consequences of ETB receptor activation may be mediated by multiple affinity states of the receptor. The present data demonstrate that [125I]BQ3020 is a potent and selective agonist for the ETB receptor that can discriminate high and low affinity states of the ETB receptor. PMID- 7882016 TI - Immunoelectron microscopy of enkephalinergic innervation of GABAergic neurons in the periaqueductal gray. AB - The pre-embedding double immunoreaction method was used to study synaptic relations of enkephalinergic and GABAergic neuronal elements in the ventrolateral part of the periaqueductal gray of the Wistar albino rat. The enkephalin-like neuronal elements were immunoreacted by the silver-gold intensified peroxidase antiperoxidase method and the GABA-like immunoreactive neurons were immunoreacted by the unintensified peroxidase-antiperoxidase method. GABA-like immunoreactive neuronal somata were post-synaptic to both the enkephalin-like immunoreactive and the non-immunoreactive axon terminals. Enkephalin-like immunoreactive axon terminals were found to make synapses with GABA-like immunoreactive and non immunoreactive dendrites. The synapses between the two kinds of chemically characterized neurons appeared to be both asymmetrical and symmetrical. Possible functional activity related to pain modulation, and synaptic relations between the enkephalinergic and GABAergic neurons in the periaqueductal gray and the dorsal raphe nucleus, are discussed. PMID- 7882017 TI - Effects of glutamatergic agonists and antagonists on membrane potential and intracellular Na+ activity of leech glial and nerve cells. AB - The membrane potential of neuropile glial cells and Retzius neurones in the central nervous system of the leech Hirudo medicinalis was measured using electrolyte-filled single-barreled microelectrodes. Intracellular Na+ activity (aNai) was recorded with Na(+)-sensitive double-barreled microelectrodes. Bath application of kainate, quisqualate and L-glutamate elicited concentration dependent membrane depolarizations in both cell types as demonstrated by dose response curves. The competitive quinoxalinedione antagonists 6,7 dinitroquinoxaline-2,3-dione (DNQX) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) to the non-NMDA glutamate receptor inhibited the membrane depolarizations in neuropile glial cells completely, but in Retzius neurones only partially. These results confirm that leech neuropile glial cells have a kainate- and quisqualate-preferring non-NMDA glutamate receptor similar to that in the Retzius neurones. The initial decrease in aNai in neuropile glial cells in kainate- or quisqualate-containing solutions and the afterhyperpolarization in these glial cells and the Retzius neurones following the removal of both glutamate antagonists, were blocked in the presence of the cardiac glycoside ouabain (10( 4) M). In saline solutions containing 42.5 mM Li+ instead of Na+ the afterhyperpolarizations were blocked in neuropile glial cells and Retzius neurones. We conclude that the initial aNai changes and the afterhyperpolarization could be due to the stimulation of the electrogenic Na+/K+ pump in the glial and neuronal membranes. PMID- 7882018 TI - Catecholamine release in the rat hypothalamic paraventricular nucleus in response to haemorrhage, desipramine and potassium. AB - In vivo microdialysis and HPLC were used to measure catecholamine release in the rat hypothalamic paraventricular nucleus (PVN) during haemorrhage. The effects of noradrenaline uptake blockade with 1 microM desipramine (DMI) and a depolarising concentration of potassium (100 mM) through the probe were also examined. Dialysis probes implanted in the PVN of urethane anesthetised rats were perfused with modified Ringer solution at 1.1 microliter/min. Thirty minute collections were analysed for DOPA, noradrenaline, DOPAC, HVA and 5-HIAA. Basal concentrations, in the absence of DMI, were: DOPA 203.6 +/- 44.0 pg/ml, noradrenaline 128.0 +/- 20.4 pg/ml; DOPAC 5.6 +/- 0.7, HVA 5.1 +/- 2.2 and 5-HIAA 87.2 +/- 17.8 ng/ml. Basal noradrenaline was doubled in the presence of DMI while basal and stimulated DOPA, DOPAC, HVA and 5-HIAA were not affected by DMI. Haemorrhage resulted in a significant noradrenaline release (48% over resting levels) in the presence of DMI (n = 10, P < 0.05); in the absence of DMI, a smaller and non-significant increase (30% over basal levels) was observed. Potassium-induced depolarisation caused a significant two- and four-fold increase in noradrenaline release (P < 0.001), with decreases in the dopamine metabolites DOPAC (31%, 44%) and HVA (35%, 28%), and the serotonin metabolite, 5-HIAA (41%, 33%), in the presence and absence of DMI, respectively. The catecholamine precursor DOPA did not vary throughout either experiment. The results indicate that haemorrhage induces a 48% increase in noradrenaline release in the rat PVN which provides evidence for a role of noradrenergic projections to the PVN in cardiovascular control. PMID- 7882019 TI - Effects of kainic acid in the parabrachial region for ongoing respiratory activity and reflexive respiratory suppression. AB - We previously reported that the electrical stimulation of gastrocnemius muscle nerve afferents given at a suprathreshold intensity for C-fiber afferents induces naloxone-reversible reflexive respiratory suppression ('after suppression'). The effects of kainic acid (KA) microinjections into the parabrachial area (nucleus parabrachialis lateralis: NPBL and nucleus parabrachialis medialis: NPBM) on (1) ongoing respiratory activity and (2) the 'after suppression' were studied in chloralose-urethane anesthetized, bivagotomized, paralyzed, and artificially ventilated cats. A large dose of KA (1.91 nmol in 0.1 microliters) microinjected into the unilateral NPBL induced significant long-lasting respiratory facilitation, while a subsequent KA injection into the ipsilateral NPBM induced significant, long-lasting respiratory depression. A small dose of KA (0.48 nmol in 0.1 microliters) into the unilateral NPBL (right side) induced significant respiratory facilitation, and the 'after suppression' effect was eliminated. A small dose into the unilateral NPBM (right side) caused initial transient respiratory facilitation followed by respiratory depression before 'after suppression' was restored. Subsequent KA injections into the NPBL on the other side (left side) significantly augmented respiration. The 'after suppression' effect was again eliminated after an injection of KA into the bilateral NPBL. It was concluded that NPBL may exhibit tonic inhibitory activities on respiration and play a critical role in the 'after suppression' effect, since an injection of KA into the NPBM counteracted both of these effects in the NPBL. PMID- 7882020 TI - NMDA receptor responses in adult hippocampal CA1 region after neonatal treatment with MK-801: comparison with NMDA receptor responses in the immature rat. AB - Neonatal MK-801 treatment from postnatal day 8-19 leads to long-term effects on brain function, suggesting that exposure to this drug leads to the development of a brain with immature network properties. One aspect of this hypothesis, that the NMDA receptors preserve their immature state after the treatment, has been tested by measuring the potency of the competitive antagonist D-AP5 in hippocampal slices. We have previously shown that an increased potency to D-AP5 is a characteristic property of NMDA receptors during early life. In the present study we measured field potentials in the CA1 region of rat hippocampal slices evoked by iontophoretic NMDA application in the Schaffer-commissural synaptic fields. Agonist dose-response curves were constructed, followed by bath applications of increasing concentrations of the antagonist D-AP5. The maximum NMDA evoked field response was the same in slices of mature control (PND70-90; 18.9 +/- 1.2 mV) and MK-801 treated rats (PND70-90; 19.3 +/- 0.9 mV), but significantly larger in immature slices (PND10-16; 24.0 +/- 0.6 mV). The sensitivity to NMDA in hippocampal slices from each group was estimated by quantifying the ionotophoretic ejection current (= dose) which evoked 50% of the maximum field response (EC50). A significantly higher sensitivity to NMDA was found in hippocampal slices obtained from MK-801-treated rats (EC50 = 3.6 +/- 0.2 nA) than in slices from control (EC50 = 6.1 +/- 0.7 nA) or immature (EC50 = 5.9 +/- 0.5 nA) animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882021 TI - Bradykinin excites tetrodotoxin-resistant primary afferent fibers. AB - Bradykinin is a nonapeptide that plays a central role in the production of pain and inflammation. A horizontal spinal cord slice preparation with attached dorsal root and dorsal root ganglion was used to study the effect of bradykinin on afferent fibers. Intracellular recordings were made from dorsal root ganglion and dorsal horn neurons. Bath application of bradykinin (1 microM) to the dorsal root ganglion compartment produced a depolarization (5 +/+ 0.8 mV) and firing of action potentials in eight out of eighteen dorsal root ganglion neurons tested. Simultaneous intracellular recordings from dorsal horn neurons revealed that the application of bradykinin to dorsal root ganglion, peripheral nerve trunk or dorsal root resulted in the synaptic activation of dorsal horn neurons. The depolarizing effect of bradykinin on the dorsal root ganglion neurons and its synaptic excitatory effect on dorsal horn neurons was abolished by pretreatment of the same segment of sensory neurons by a B2 bradykinin receptor antagonist (D Arg0,Hyp3,beta-Thi5,8,D-Phe7)-bradykinin (5 microM). Bath application of tetrodotoxin (TTX; 0.2-1 microM) to the sensory neurons blocked electrically evoked action potentials in large dorsal root ganglion neurons and, consequently, excitatory postsynaptic potentials in dorsal horn neurons evoked by electrical activation of low threshold afferent fibers. However, the stimulatory effects, both depolarization and firing of action potentials, of bradykinin were resistant to TTX. Replacement of sodium ions with TRIS completely abolished the stimulatory effect of bradykinin on the sensory neurons. Bradykinin potentiated the postsynaptic potentials induced by electrical stimulation of TTX-resistant afferent fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882022 TI - Tetrahydrobiopterin uptake into rat brain synaptosomes, cultured PC12 cells, and rat striatum. AB - The uptake of (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) was investigated in rat brain synaptosomes, cultured rat pheochromocytoma (PC12) cells, and rat striatum (control and depleted of dopamine neurons) following peripheral administration. A linear, non-saturable, concentration-dependent intracellular accumulation was observed when BH4 was added to either synaptosomes or PC12 cells. The uptake of BH4, in contrast to that of serotonin uptake into synaptosomes or norepinephrine (NE) uptake into PC12 cells, was not dependent on glucose or extracellular sodium. Stimulation of tryptophan hydroxylation in synaptosomes by incubation with 5 microM tryptophan (which increases utilization of BH4 in serotonergic cells) did not alter BH4 uptake. In rats with unilateral 6-hydroxydopamine (6 OHDA) lesions of dopamine neurons, BH4 uptake was the same in control and lesioned striatum following peripheral administration. These results indicate that neurons and PC12 cells do not appear to have a specific membrane carrier for BH4 and that BH4 uptake into cells is due to passive diffusion. PMID- 7882023 TI - Mu and delta opioid synergy between the periaqueductal gray and the rostro ventral medulla. AB - Microinjection of [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO) into either the periaqueductal gray (PAG) or the rostral ventral medulla (RVM) elicits analgesia in the tailflick assay in the rat. Co-administration of DAMGO into both regions together results in a profound synergistic interaction similar to that we previously reported with morphine. U50,488H and DPDPE are inactive when given into either region. [D-Ala2,Glu4]Deltorphin (deltorphin), on the other hand, elicits an analgesic response, although the maximal response is less than than mu agonists. Co-administration of DAMGO into one region with deltorphin in the other also results in a significant synergy. However, co-administration of DAMGO and deltorphin together in the same region gives only additive effects. These results confirm the existence of mu/mu synergy between the PAG and RVM. kappa 1 and delta 1 agents are inactive, but the delta 2 agonist deltorphin is active in both regions. Our results indicate the presence of mu/delta 2 synergy between the PAG and RVM which appears to involve interactions of pathways rather than receptor interactions at the cellular level. PMID- 7882024 TI - Characterization of a triple opioid system in the human neuroblastoma NMB cell line. AB - The human neuroblastoma NMB cell line was found to contain the three types of opioid receptors (60% delta 25% kappa and 15% mu). The opioid receptors were negatively coupled to adenylyl-cyclase. Maximal reduction in cAMP content was achieved by selectively activating single receptor types, indicating the co presence of the various opioid receptors in the same cells. The opioid receptors in NMB cells were up-regulated following prolonged exposure to the opioid antagonist naloxone and down-regulated following chronic treatment with the opioid agonist etorphine. Down-regulation was time-, dose- and temperature dependent and was inhibited by colchicine and sodium azide. The NMB culture is presented as an excellent experimental model for studying the selective activation and regulation of the different opioid receptor types when they are co expressed in the same neuron, as well as for studying interactions between the various opioid receptors. PMID- 7882025 TI - Synaptotrophic effects of human amyloid beta protein precursors in the cortex of transgenic mice. AB - The amyloid precursor protein (APP) is involved in Alzheimer's disease (AD) because its degradation products accumulate abnormally in AD brains and APP mutations are associated with early onset AD. However, its role in health and disease appears to be complex, with different APP derivatives showing either neurotoxic or neurotrophic effects in vitro. To elucidate the effects APP has on the brain in vivo, cDNAs encoding different forms of human APP (hAPP) were placed downstream of the neuron-specific enolase (NSE) promoter. In multiple lines of NSE-hAPP transgenic mice neuronal overexpression of hAPP was accompanied by an increase in the number of synaptophysin immunoreactive (SYN-IR) presynaptic terminals and in the expression of the growth-associated marker GAP-43. In lines expressing moderate levels of hAPP751 or hAPP695, this effect was more prominent in homozygous than in heterozygous transgenic mice. In contrast, a line with several-fold higher levels of hAPP695 expression showed less increase in SYN-IR presynaptic terminals per amount of hAPP expressed than the lower expressor lines and a decrease in synaptotrophic effects in homozygous compared with heterozygous offspring. Transgenic mice (2-24 months of age) showed no evidence for amyloid deposits or neurodegeneration. These findings suggest that APP may be important for the formation/maintenance of synapses in vivo and that its synaptotrophic effects may be critically dependent on the expression levels of different APP isoforms. Alterations in APP expression, processing or function could contribute to the synaptic pathology seen in AD. PMID- 7882026 TI - Magnesium suppresses neuropathic pain responses in rats via a spinal site of action. AB - We tested the ability of Mg2+ therapy to block the heat-hyperalgesia, mechano allodynia and mechano-hyperalgesia that are seen in rats with an experimental painful peripheral neuropathy (the CCI model of Bennett and Xie). Systemic Mg2+ (magnesium sulfate, 600 mg/kg, s.c.) significantly reduced heat-hyperalgesia and mechano-allodynia for 2-24 h post-injection, but had no effect on mechano hyperalgesia. Intrathecal (i.t.) injections of Mg2+ (185-750 micrograms) at the level of the lumbar spinal cord significantly reduced heat-hyperalgesia, but perineural application (750 and 7,000 micrograms) to the site of nerve injury had no effect. Neither s.c. nor i.t. Mg2+ had any effect on the responses from the control, sham-operated side. We conclude that Mg2+ has a spinal site of action. Mg2+ therapy may be of limited use in the treatment of human painful peripheral neuropathy. PMID- 7882027 TI - Immunohistochemical localization of Ca2+/calmodulin-dependent protein kinase type IV in the peripheral ganglia and paraganglia of developing and mature rats. AB - The immunohistochemical localization of Ca2+/calmodulin-dependent protein kinase type IV (CaM kinase IV) was examined in rat peripheral ganglia and paraganglia as well as brain. In sensory ganglia including the trigeminal and dorsal root ganglia, small- to medium-sized neurons were intensely immunoreactive. In the spinal cord, immunoreactive small neurons were seen in superficial laminae of the dorsal horn, whereas motoneurons were immunonegative. In autonomic ganglia including the superior cervical, celiac, and submandibular ganglia, almost all neurons were intensely immunoreactive for CaM kinase IV. In the small intestine, immunoreactive neurons were seen in the submucosal and myenteric ganglia. In all immunoreactive neurons, the immunoreactivity was localized predominantly in cell nuclei, whereas nucleoli and nerve fibers were completely free from immunoreaction. From the wide distribution and predominant nuclear localization of CaM kinase IV, it is suggested that CaM kinase IV might be involved in the modulation of gene transcription through the nuclear Ca(2+)-signaling in the peripheral as well as central nervous system. PMID- 7882028 TI - Antinociceptive effect of intrathecally administered P2-purinoceptor antagonists in rats. AB - To investigate whether ATP participates in spinal nociceptive transmission, effects of intrathecally applied P2-purinoceptor antagonists and agonists in the tail-flick and the formalin test were studied in rats. In the tail-flick assay, the P2 antagonists suramin (12-120 micrograms), Evans blue (0.1-10 micrograms), Trypan blue (1-30 micrograms) and Reactive blue 2 (1-30 micrograms) but not pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 0.03-30 micrograms) caused moderate antinociception up to a doubling of the response latency. In contrast, the P2 agonists alpha,beta-methylene ATP (alpha,beta-mATP, 0.3-30 micrograms) and 2-methylthio-ATP (3-30 micrograms) decreased the tail-flick latency by up to about 50%. When co-injected with alpha,beta-mATP, suramin (120 micrograms) or Evans blue (10 micrograms) prevented the effect of alpha,beta-mATP 3 micrograms but not of alpha,beta-mATP 30 micrograms. In the formalin test, pretreatment with suramin (3-90 micrograms) 60 min prior to testing caused significant antinociception by decreasing the weighted pain intensity score by up to about 80%. alpha,beta-mATP (30 micrograms), applied 30 min prior to testing, was without effect. The results indicate that endogenous ATP, acting through P2 purinoceptors, may contribute to nociceptive information processing in the spinal cord. PMID- 7882030 TI - N-methyl-D-aspartate (NMDA) stimulates release of alpha-MSH from the rat hypothalamus through release of nitric oxide. AB - Superfusion of rat hypothalamic slices with 10(-4) M N-methyl-D-aspartic acid (NMDA) resulted in increased release of alpha-melanocyte-stimulating hormone (alpha-MSH). Peptide release was blocked by 10(-6) M NG-nitro-L-arginine methyl ester (L-NAME) a specific competitive inhibitor of nitric oxide synthase but not by the inactive enantiomer D-NAME at 10(-6) M. The inhibition by L-NAME was reversed by the addition of 10(-5) mM L-arginine, an excess of enzyme substrate. Release of nitric oxide products into tissue superfusates was stimulated by a 50 mM concentration of potassium ions and by 10(-4) M NMDA. Potassium-stimulated release was blocked by L-NAME. Basal, potassium-stimulated and NMDA-stimulated release of nitric oxide products were significantly inhibited by the NMDA receptor antagonist D(-)-2-amino-5-phosphopentanoic acid (AP5) at 10(-4) M and by the NMDA-channel blocker ketamine at 10(-4) M. We conclude that nitric oxide mediates the stimulatory action of glutamic acid on the release of alpha-MSH from the rat hypothalamus. PMID- 7882029 TI - Noradrenergic lesioning with an anti-dopamine beta-hydroxylase immunotoxin. AB - Sympathectomy has been achieved by a variety of methods but each has its limitations. These include lack of tissue specificity, incomplete lesioning, and the age range of susceptibility to the lesioning. To circumvent these drawbacks, an immunotoxin was constructed using a monoclonal antibody against the noradrenergic specific enzyme dopamine beta-hydroxylase (D beta H) coupled via a disulfide bond to saporin, a ribosomal inactivating protein. Three days after intravenous injection of the anti-D beta H immunotoxin (50 micrograms) into adult Sprague-Dawley rats, 66% of neurons in the superior cervical ganglia were chromatolytic. Superior cervical ganglia neurons were poisoned in 1 day old and 1 week old (86% of neurons) neonatal rats following subcutaneous injection of 3.75 and 15 micrograms, respectively. The anti-D beta H immunotoxin will be a useful tool in the study of the peripheral noradrenergic system in adult and neonatal animals. PMID- 7882031 TI - Differential patterns of local cerebral glucose utilisation associated with rilmenidine- or B-HT 933-induced hypotension. AB - The anti-hypertensive drug, rilmenidine, has activity at both imidazoline preferring receptors (IPRs) and alpha 2-adrenoceptors. However, available evidence suggests that its hypotensive effect is mediated via central IPRs. In the present study, the neuroanatomical regions involved in mediating the hypotensive response to rilmenidine were investigated using the [14C]2 deoxyglucose in vivo autoradiographic technique to map drug-induced changes in glucose utilisation within the CNS of conscious, spontaneously hypertensive rats (SHR). The cerebral metabolic effects of rilmenidine were compared with those of B-HT 933, a selective, alpha 2-adrenoceptor agonist with no selectivity for the IPR. Rilmenidine (1 mg/kg, s.c.) and B-HT 933 (2 mg/kg, s.c.) both elicited a moderate but significant hypotension (-24 +/- 2 and -18 +/- 5 mmHg, resp.) and bradycardia (-62 +/- 19.5 and -69 +/- 14 beats/min, resp.). [14C]2-deoxyglucose autoradiography, initiated after stabilisation of the drug-induced reduction in blood pressure, revealed significant reductions (P < 0.05) in local cerebral glucose utilisation (LCGU) in the intermediolateral cell column of the spinal cord, area postrema, ventrolateral medulla, nucleus tractus solitarius and cuneate nucleus of rilmenidine-treated rats. Rilmenidine did not significantly alter LCGU in a number of structures containing high densities of alpha 2 adrenoceptors such as nucleus accumbens, locus coeruleus, frontal cortex. No significant changes in glucose use were evident in any of the 26 CNS regions examined following B-HT 933 administration. These results provide evidence for the functional involvement of brainstem cardiovascular control centres in the central hypotensive effects of rilmenidine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882032 TI - MK-801 does not prevent acute stimulatory effects of amphetamine or cocaine on locomotor activity or extracellular dopamine levels in rat nucleus accumbens. AB - Recent work has shown that the development of behavioral sensitization to cocaine, amphetamine, and morphine is prevented by coadministration of N-methyl-D aspartate (NMDA) antagonists such as MK-801. This suggests that NMDA receptors mediate long-term changes in neuronal responsiveness essential for the development of behavioral sensitization, similar to their role in other forms of neuronal plasticity. However, other studies, suggesting that NMDA receptor antagonists interfere with acute behavioral effects of psychomotor stimulants, call this interpretation into question and suggest that the ability of NMDA antagonists to prevent sensitization may reflect blockade of the acute effects of psychomotor stimulants. To examine this issue, behavioral and microdialysis studies assessed the effect of pretreatment with 0.1 mg/kg MK-801 on the ability of amphetamine and cocaine to stimulate locomotor activity and elevate extracellular dopamine (DA) levels in nucleus accumbens; this dose of MK-801 prevents sensitization when coadministered repeatedly with these stimulants. MK 801 pretreatment enhanced amphetamine-stimulated horizontal locomotion and stereotyped behavior. MK-801 pretreatment produced a modest attenuation of cocaine-stimulated horizontal locomotion, which may have reflected enhancement by MK-801 of certain components of cocaine-stimulated stereotypy. There was no effect of MK-801 pretreatment on the ability of amphetamine or cocaine to elevate extracellular DA levels in nucleus accumbens. These results suggest that the acute effects of cocaine and amphetamine on locomotor activity and extracellular DA levels are not prevented by MK-801, and that MK-801 must act through other mechanisms to prevent the development of behavioral sensitization. PMID- 7882033 TI - Effect of stress and long-term potentiation (LTP) on subsequent LTP and the theta burst response in the dentate gyrus. AB - Exposure to an aversive and stressful event is reported to have similar effects on hippocampal plasticity and behavior as does exposure to high-frequency stimulation of the hippocampus. Here we directly compared the effects of exposure to a stressor vs. a previous induction of LTP on a subsequent induction of LTP and the extracellular response to a tetanus patterned after endogenous theta rhythms. Stimulating the dentate gyrus via the perforant path, Sprague-Dawley rats (n = 65) were tetanized 2 h after exposure to a stressor consisting of restraint and 60, 1, s, 1 mA tail shocks. Unstressed controls were tetanized once and then again 2 h later. Exposure to the stressor impaired LTP of the EPSP 2 h later, as did a previous induction of LTP. In addition, exposure to the stressor altered the extracellular response to subsequent theta burst stimulation (10, 40 ms bursts at 100 Hz, each separated by 200 ms), as did a previous induction of LTP. Whereas unstressed rats exposed to the first tetanus exhibited a marked decline in the amplitude across successive bursts, stressed rats exhibited no such decline, a response pattern similar to that observed in unstressed rats exposed to a second tetanus. The similarity between the effects of stress and tetanic stimulation on hippocampal plasticity support the hypothesis that stress and LTP are converging on similar neuronal mechanisms. PMID- 7882034 TI - In vitro electrophysiological characterization of midbrain periaqueductal gray neurons in female rats: responses to GABA- and Met-enkephalin-related agents. AB - Met-Enkephalin, which can be induced by estrogen in the ventromedial nucleus of hypothalamus (VMH), has been proposed to help mediate estrogenic action on lordosis behavior by acting on midbrain periaqueductal gray (PAG) neurons. Also, in the PAG, GABA may locally regulate the levels of lordosis behavior through GABAA receptors. Therefore, we examined the effects of both Met-enkephalin and GABA-related agents on neuronal activity of PAG neurons in slices. Overall, 72.6% of the PAG neurons were inhibited by GABA and 60.9% of GABA-responsive neurons were also excited by the GABAA receptor antagonist, bicuculline methiodide (BMI), suggesting that many of GABA-responsive PAG neurons are tonically inhibited by GABAergic neurons through GABAA receptors. Dorsal PAG neurons were more responsive to BMI than ventral PAG neurons. Moreover, in the middle part of the dorsal PAG, where prominent inhibitory behavioral effects of BMI have been reported, BMI excited 94% of GABA-responsive PAG neurons from estrogen-treated animals, significantly more than observed in ovariectomized control (50%). The most frequent action of Met-enkephalin on PAG neurons was inhibitory (38 out of 149 recorded neurons) although it excited 12 neurons. A dose-dependent increase of inhibitory action of enkephalin was found in the estrogen-primed group but not in the ovariectomized control group while higher doses of enkephalin failed to excite any more neurons in both groups. Most frequently (90%), enkephalin inhibited the same neurons as those on which GABA had the inhibitory effects. Conversely, these neurons composed about 50% of the entire GABA-responsive PAG neurons. Moreover, 76% of neurons inhibited by enkephalin were found to be tonically inhibited by endogenous GABA through GABAA receptors. It is argued, therefore, that increased enkephalinergic influences from the VMH to the PAG in estrogen-treated females could participate in the PAG neuronal control of lordosis by acting on the same neurons as are innervated by intrinsic GABAergic neurons. Since GABAA agonists actually facilitate lordosis in the PAG, these PAG neurons inhibited by both GABA and enkephalin may themselves facilitate behaviors which are antagonistic to lordosis, such as defensive behaviors. PMID- 7882035 TI - Pre-degenerated nerve grafts enhance regeneration by shortening the initial delay period. AB - In the present study we tested how nerve grafts with different pre-degeneration periods (1-28 days) influenced the early regenerative response in the rat sciatic nerve. The sciatic nerve on the right side was crushed and after 1-28 days of pre degeneration, a 10 mm segment was used as an autologous nerve graft and transposed to a freshly made 10 mm long nerve defect on the left side. The regeneration distance was measured by the sensory pinch test 2-10 days after nerve repair. A newly developed mathematical model was used to calculate regeneration rates and initial delay periods from the measured regeneration distances. Pre-degenerated nerve grafts improved nerve regeneration by decreasing the initial delay period as compared to fresh nerve grafts without affecting the regeneration rate. Only one day of pre-degeneration was sufficient to reduce the initial delay period from 3.6 days to 1.7 days. The maximal effect on the initial delay period was achieved after 3 days of pre-degeneration. The initial delay period at later pre-degeneration intervals (7-14 days) was about 1 day. The effect persisted for at least 28 days of pre-degeneration. The regeneration rate was 1.5 mm/day for fresh nerve grafts and between 1.8-2.1 mm/day for pre degenerated grafts. The results suggest that the effects of pre-degeneration are not only due to the increased cell proliferation in the graft, but that also trophic and/or inflammatory mechanisms may be of importance. Grafts pre degenerated by crush may have clinical implications since they are easy to perform if an elective nerve grafting procedure is planned. PMID- 7882036 TI - N-methyl-D-aspartic acid biphasically regulates the biochemical and electrophysiological response of A10 dopamine neurons in the ventral tegmental area: in vivo microdialysis and in vitro electrophysiological studies. AB - The effects of local perfusion of the ventral tegmental area (VTA) with N-methyl D-aspartic acid (NMDA) on extracellular dopamine concentrations in the nucleus accumbens were investigated by using in vivo microdialysis in halothane anaesthetized rats. The electrophysiological response of VTA dopamine neurons to NMDA were also assessed in an in vitro rat brain slice preparation. In both preparations NMDA elicited a biphasic response. Exposure of the VTA to low doses of NMDA (< 100 microM) elicited increases in dialysate dopamine levels in the nucleus accumbens and increases in the firing rate of VTA dopamine neurons. Larger doses (> 100 microM) resulted in profound reductions in both dopamine release in the accumbens and firing in the VTA. A strong correlation between the ability of NMDA to influence dopamine release in the accumbens and the firing rate in the VTA was observed. Perfusion with the non-competitive NMDA receptor antagonist PCP eliminated the NMDA-induced increases in extracellular dopamine in the accumbens. These data suggest that dopamine release in the accumbens and the firing rate of dopamine neurons can be both increased or decreased depending upon the magnitude of glutamatergic stimulation within the VTA. PMID- 7882037 TI - Prior mechanical injury inhibits rise in intracellular Ca2+ concentration by oxygen-glucose deprivation in mouse hippocampal slices. AB - Prior mechanical brain microinjury has been found to have a preventive effect on brain ischemia. To investigate the mechanism responsible for this, the effect of mechanical brain injury on changes in intracellular free Ca2+ concentration ([Ca2+]i) in response to ischemic insult was studied in mouse hippocampal slices. The mechanical injury was made by inserting a 25G hypodermic needle into the CA1 region of the hippocampus in mice anesthetized with pentobarbital. Sagittal slices of the hippocampus were prepared two hours, and 1, 3, 7, and 14 days after the brain injury. Changes in [Ca2+]i in the slices by oxygen-glucose deprivation were analyzed from fluorescence images, using fura-2. Increases in [Ca2+]i induced by oxygen-glucose deprivation were inhibited in the vicinity of the injury 1 and 3 days after injury. [Ca2+]i levels were lower in the posterior side from the injury than in the anterior side 1 and 3 days after injury. No significant regional differences in [Ca2+]i responses were found 2 h or 7 and 14 days after the injury. Membrane potential and membrane resistance of CA1 neurons in the vicinity of the injury measured 1 day after the injury were not significantly altered in comparison with non-injured slices. These results indicate that mechanical brain injury inhibits ischemic [Ca2+]i increase. This inhibition may be induced not only by damage of the presynaptic fibers projecting to the CA1 neurons but also by the other certain factor(s) that prevent [Ca2+]i increase, and it appears to be related to the protective effect of prior mechanical injury against ischemic neuronal damage. PMID- 7882038 TI - Classification of inhibitory responses of the hamster gustatory cortex. AB - Neuronal activity was recorded in the gustatory cortex of the golden Syrian hamster in response to application of taste stimuli to the anterior tongue. Two classes of inhibitory responses were detected: (1) a decrease in activity in response to application of individual taste stimuli: and (2) a decrease in activity in response to application of a mixture of taste stimuli but not in response to application of individual taste stimuli. PMID- 7882039 TI - Rostro-caudal distribution of reticulospinal projections from different brainstem nuclei in the lamprey. AB - The reticulospinal (RS) system in the lamprey is responsible for the control of locomotion, postural corrections and steering. To perform these functions, the RS system has to affect different muscular compartments along the body axis selectively. In this study, the possibility that RS neurones in different nuclei may project to different parts of the spinal cord, was investigated. The rostro caudal extent of single RS axons was defined by stimulating them antidromically while recording from their cell body. All recorded mesencephalic RS neurones projected to the caudal tip of the spinal cord. Of the rhombencephalic RS neurones, 26% of the recorded neurones did not reach the caudalmost fourth of the spinal cord and this proportion varied between the anterior (18%), middle (17%) and posterior (36%) rhombencephalic reticular nuclei. For these RS axons, the level of termination covered the whole rostro-caudal extent of the spinal cord. No correlation was found between the length of an axon and its conduction velocity or between the length of an axon and the rostro-caudal position of its cell body in the nuclei. PMID- 7882040 TI - Histamine depletion in brain caused by treatment with (S)alpha fluoromethylhistidine enhances ischemic damage of gerbil hippocampal CA2 neurons. AB - The effect of (S)alpha-fluoromethylhistidine (FMH), a specific inhibitor of histamine synthesis from histidine, on ischemic damage was examined in gerbil brain after forebrain ischemia. Two h after subcutaneous FMH injection, the histamine content of the brain was significantly reduced. Neuronal loss in the CA2 region of the hippocampus 7 days after 3 min ischemia was enhanced by treatment with FMH. These results indicate that depletion of brain histamine aggravates neuronal death of hippocampal CA2 neurons after 3 min ischemia. PMID- 7882041 TI - Lesions in the medial posterior region of the BST impair sexual behavior in sexually experienced and inexperienced male rats. AB - Previous studies have showed that lesions in the bed nucleus of the stria terminalis of experienced male rats impair some parameters of sexual behavior. The aim of this study was to examine the contribution of the medial posterior region of the bed nucleus of the stria terminalis (BSTMP), a sexually dimorphic region of this nucleus that pertains to the vomeronasal system, to the modulation of sexual behavior of the male rat. Small electrolytic bilateral lesions in the BSTMP were made in male heterosexual experienced and inexperienced rats. Sham lesioned animals were also tested as a control of the effects of the general surgical procedures. Behavioral tests were then performed to obtain standard measures of masculine sexual behavior. Our results indicate that the sexually experienced male rats with lesioned BSTMPs showed increases in the number of mounts and the number of intromissions and, consequently, in ejaculation latency. In contrast, the sexually naive male rats showed increases in first mount and intromission latencies and in ejaculation latency, but the latter occurred due to increases in the interintromission intervals. This group also showed low correlations between olfactory investigation of the anogenital area of the female and initiation and maintenance of copulatory behavior. The results suggest that sexual experience obtained in the very artificial conditions of laboratory tests could supply some of the cues provided by the BSTMP in the process of sensorial integration, which we hypothesize modulates the initiation and pacing of copulation. However, sexual experience does not apparently supply any other kinds of cues provided or processed in the BSTMP that are involved in modulating the elicitation of intromissions and ejaculations. PMID- 7882042 TI - A simple and reliable method for construction of parallel multibarrel microelectrodes. AB - A modification to the method of construction of parallel or "piggy-back" electrodes for extracellular single-unit recording combined with iontophoresis is described that facilitates the alignment of the two components of the array. The method involves the use of an orthogonal viewing device (a pair of mirrors mounted symmetrically at 45 degrees to the horizontal), which produces a pair of virtual images of the electrode components that can be viewed with a microscope. A slight displacement between the electrodes is easily detected as an uneven separation between the electrode images. The positions of the electrode components are adjusted until there is no visible separation of the electrodes or their virtual images. PMID- 7882043 TI - Enhanced isolation of Tyr-MIF-1 from fresh human brain cortex. AB - Tyr-MIF-1 previously was isolated from tissue obtained after death. A possible role of autolysis could not be excluded. We report the isolation of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) in increased amounts from fresh human brain cortex. This confirms the natural existence of this brain peptide. PMID- 7882044 TI - Passive avoidance learning induced change in GAP43 phosphorylation in day-old chicks. AB - Day-old chicks trained on a single trial passive discriminated avoidance task demonstrated a significant increase in in vitro phosphorylation of a 50 kDa protein in P2M fractions of total forebrain. The increase occurred 30 min posttraining, at a time when previous reports suggest that mechanisms for triggering protein synthesis-dependent long-term memory consolidation are activated. These changes in phosphorylation rates were accompanied by a substantial enhancement of total kinase activity. Immunoblotting studies with monoclonal anti-GAP43 antibody indicate that this protein is GAP43. These results contradict previous reports of a decrease in in vitro GAP43 phosphorylation following the same learning paradigm. A number of procedural differences may account for this discrepancy. The results suggest that changes in the phosphorylation state may be associated with mechanisms triggering long-term memory consolidation. PMID- 7882045 TI - CRH and the noradrenergic system mediate the antinociceptive effect of central interleukin-1 alpha in the rat. AB - After intracerebroventricular administration, both interleukin-1 alpha and corticotropin-releasing hormone increase nociceptive thresholds evaluated by the hot-plate test in the rat. Pretreatment with 6-hydroxydopamine or prazosin fully prevents the action of both substances. Moreover, the effect of interleukin-1 alpha is completely blocked by the intracerebroventricular administration of the corticotropin-releasing hormone antagonist alpha-helical CRH 9-41. Our results suggest an involvement of CRH and the noradrenergic system in the antinociceptive effect of central interleukin-1 alpha. PMID- 7882046 TI - The effect of pleasant odors and hormone status on mood of women at midlife. AB - The effect of odors on the mood of 56 women ranging in age from 45 to 60 years was determined using the POMS (Profile of Mood States). The 56 subjects were divided into four groups of 14 subjects each on the basis of hormonal status. Group 1 consisted of 14 women who were still menstruating; group 2 consisted of 14 women who were no longer menstruating and taking estrogen; group 3 consisted of 14 women who were no longer menstruating and taking estrogen and progesterone; and, group 4 consisted of 14 women who were no longer menstruating and taking no hormone replacement. Use of pleasant odors significantly improved scores on tension, depression, and confusion factors. In addition, women using estrogen replacement with or without progesterone had better mood scores than those who did not, which is consistent with previous studies. PMID- 7882047 TI - Effect of pleasant odors on mood of males at midlife: comparison of African American and European-American men. AB - The purpose of this study was to determine if daily use of colognes could elevate mood in middle-aged men. Sixty men ranging in age from 40 to 55 years participated in the study. Half were European-American and half were African American. Mood ratings were obtained twice daily for 12 days using the Profile of Mood States questionnaire (POMS). The first 2 days of the experiment were used as baseline information to establish each man's mood prior to the administration of the colognes. The following 10 days of the study consisted of two conditions of 5 days each, the fragrance condition and the placebo condition. Main effects of condition (baseline, fragrance, placebo) were found for all POMS factors including tension, depression, anger, vigor, fatigue, and confusion, as well as for the Total Mood Disturbance score (TMD). The scores for the fragrance condition were significantly better than those for the baseline condition for tension, depression, anger, fatigue, and confusion factors, as well as for the TMD. Also, the scores for the fragrance condition were significantly better than those for the placebo condition for all factors and the TMD. There was a main effect for race, with European-American subjects having significantly worse scores for tension and fatigue and significantly better scores for depression than African-American subjects. An interaction was present between race and condition for the depression, vigor, and confusion factors. The main conclusion of this study was that use of pleasant odors improved the mood of males at midlife. PMID- 7882049 TI - Nucleus basalis lesions: implication of basoamygdaloid cholinergic pathways in memory. AB - Previous studies have shown a lack of association between cortical choline acetyltransferase (ChAT) activity and severity of memory impairment following excitotoxic lesions of the nucleus basalis magnocellularis (NBM). It recently has been proposed that the differential effects of NBM injections of various excitotoxins on amygdaloid and cortical ChAT may explain this result. The present study evaluated the mnemonic effect of unilateral intra-NBM infusions of the excitotoxins phthalic acid and quisqualic acid, which decrease ChAT activity primarily in the amygdala and cortex, respectively. Rats were trained in a double Y-maze, lesioned, and allowed to recover for 1 week prior to memory assessment. Behavioral results showed impaired working but not reference memory following phthalic acid lesions, and no significant effect following quisqualic acid lesions. Biochemical analysis in a second group of subjects confirmed that phthalic acid lesions produced a large decrease in basolateral amygdaloid ChAT, but had little effect on cortical ChAT activity. Conversely, quisqualic acid lesions produced a large decrease in cortical, but not basolateral amygdaloid, ChAT activity. These results suggest that the NBM amygdalopetal cholinergic pathways play a role in mnemonic functioning. PMID- 7882048 TI - Hypothalamic paraventricular, but not supraoptic neurons, mediate the serotonergic stimulation of oxytocin secretion. AB - The purpose of the present studies was to determine whether cells in the hypothalamic paraventricular (PVN) or supraoptic (SON) nuclei mediate the serotonergic stimulation of oxytocin secretion. The serotonergic stimulus consisted of injection of the 5-HT-releasing drug p-chloroamphetamine (8 mg/kg, IP). The validity of this approach was verified by comparing this drug with another 5-HT releaser, d-fenfluramine (5 mg/kg, IP). Both 5-HT releasers increased plasma oxytocin concentration. Furthermore, the 5-HT uptake blocker fluoxetine (10 mg/kg, IP) blocked the effects of both p-chloroamphetamine and d fenfluramine on plasma oxytocin concentrations, suggesting that both 5-HT releasers must be taken up through the 5-HT transporter into 5-HT nerve terminals to increase oxytocin secretion. In the lesion experiments, cells in the hypothalamic PVN or SON were destroyed by injection of the cell-selective neurotoxin ibotenic acid. The PVN lesions reduced basal levels and inhibited the effect of p-chloroamphetamine (8 mg/kg, IP) on plasma oxytocin concentration. In contrast, SON lesions did not alter basal oxytocin levels and did not reduce the oxytocin response to p-chloroamphetamine, suggesting that the SON is not involved in the serotonergic stimulation of oxytocin secretion. Site specificity of the PVN lesions was confirmed when injections of ibotenic acid into the hypothalamic dorsomedial nucleus (DMN), immediately caudal to the PVN, potentiated the oxytocin response to p-chloroamphetamine, suggesting that the DMN exerts an inhibitory influence on the secretion of oxytocin. Taken together, the data suggest that the serotonergic stimulation of oxytocin secretion involves PVN, but not SON, oxytocin neurons. PMID- 7882050 TI - Lower GABAA receptor binding in the amygdala and hypothalamus of spontaneously hypertensive rats. AB - The central GABAergic system is associated with normal blood pressure regulation, but the role of GABA receptors in genetic hypertension remains unclear. This study was conducted to investigate GABAA receptor binding in several brain regions of spontaneously hypertensive (SHR) rats during development of hypertension. GABAA receptor binding was labeled with [35S]TBPS and was assessed by quantitative autoradiography with the aid of a computer-assisted image analysis system. Densities of GABAA receptor binding sites were significantly lower in all hypothalamic and amygdaloid nuclei evaluated in 4-week-old SHR rats, when compared with their age-matched normotensive Wistar-Kyoto rats. At 12 weeks of age, GABAA receptor binding remained significantly lower in the central amygdaloid nucleus and paraventricular hypothalamic nucleus of SHR rats. Collectively, the results suggest that GABAA receptors in these nuclei are likely to be involved in the initiation and maintenance of hypertension. In conclusion, this study supports a notion that downregulation of GABAA receptor binding occurs in the hypothalamus and amygdala of SHR rats and may play a role in genetic hypertension. PMID- 7882051 TI - Adrenalectomy alters the response of neurons in the bed nucleus of the stria terminalis to electrical stimulation of the medial amygdala. AB - This study was performed to characterize the effects of adrenalectomy (ADX) on electrical activity and synaptic responses of bed nucleus of the stria terminalis (BNST) and preoptic area (POA) neurons, which are involved in the control of limbic-hypothalamo-pituitary-adrenocortical (LHPA) activity. Adrenalectomy altered the response of BNST neurons to medial amygdala (AME) stimulation, increasing the proportion of excitatory responses and reducing the number of cells inhibited. No such effects were found for neurons within the POA. The basal activity of neurons recorded within the BNST and POA, as well as the latencies and duration of responses, was not affected. The specificity of the effects upon BNST, but not POA, neurons suggests that the response of BNST neurons to AME stimulation is corticosteroid dependent, whereas the response of preoptic neurons is not. PMID- 7882052 TI - Corticotropin-releasing factor administered into the locus coeruleus, but not the parabrachial nucleus, stimulates norepinephrine release in the prefrontal cortex. AB - Previous studies have indicated that intracerebroventricular application of corticotropin-releasing factor (CRF) activates noradrenergic neurons in the brain stem locus coeruleus (LC) and norepinephrine (NE) metabolism in several brain regions. To assess whether CRF has direct effects on LC noradrenergic neurons, CRF was infused into the LC and concentrations of NE and its metabolites were measured in microdialysates collected from the medial prefrontal cortex (PFM). Infusion of 100 ng of CRF into the LC significantly increased dialysate concentrations of NE and of its catabolite MHPG in the ipsilateral PFM, whereas no significant changes were observed following infusion of artificial CSF. No response was observed when the infusions of CRF occurred outside of the LC, including those in the parabrachial nucleus. Although CRF administered into the LC slightly increased dialysate concentrations of NE in the contralateral PFM, this effect was not statistically significant. The effect of CRF injected into the LC on dialysate NE was prevented by combination with a 10-fold excess of the CRF antagonist alpha-helical CRF9-41, indicating some specificity in the response. These results are consistent with anatomical and electrophysiological evidence suggesting that CRF may directly activate noradrenergic neurons in or close to the LC. PMID- 7882053 TI - Massive activation of c-fos in forebrain after mechanical stimulation of the locus coeruleus. AB - Brief implantation of a 33-ga cannula in the locus coeruleus (LC) of the rat caused widespread and intense ipsilateral activation of c-fos throughout the forebrain. Areas showing heavy staining included the cingulate, piriform, parietal, frontal cortex, and the olfactory tubercle. Prior lesion of the LC with 6-hydroxydopamine (6-OHDA) abolished the response. It is concluded that the mechanical stimulation and/or trauma involved in the implantation of a cannula in the LC is sufficient to cause widespread activation of noradrenergic neurotransmission throughout the forebrain. The use of this procedure for drug delivery should therefore be reevaluated. PMID- 7882054 TI - Effects of suprachiasmatic lesions on temperature regulation in the golden hamster. AB - The body temperature of individually housed golden hamsters was studied by telemetry. Elimination of circadian rhythmicity by electrolytic lesions of the suprachiasmatic nuclei of the hypothalamus (SCN) did not affect the mean level of body temperature of animals maintained at 22, 12, or 6 degrees C. The range of variation of body temperature around the mean level was also found not to differ from that of intact animals that had the circadian component filtered out by a subtractive moving-averages procedure. These results indicate that the SCN plays no role in the homeostatic control of body temperature. The role of the SCN seems to be limited to the generation of circadian rhythmicity that is superimposed on the homeostatic process of temperature regulation. PMID- 7882055 TI - Amino acids in the medulla oblongata contribute to baroreflex modulation by angiotensin II. AB - We investigated the underlying mechanisms of baroreflex alteration produced by intravenous angiotensin II (ANG II) by monitoring the release of amino acids from the rostral ventrolateral medulla (VLM) using a brain microdialysis technique. Reflex changes in heart rate were elicited by bolus intravenous injection of phenylephrine (2-40 micrograms/kg) before and 120 min after the initiation of administration of a subpressor dose of ANG II (5.4 pmol/kg/min) or vehicle. The slope of the regression line obtained from changes in mean arterial pressure and heart rate elicited by phenylephrine was used as an index of baroreceptor reflex sensitivity. ANG II administration for 120 min significantly attenuated the baroreflex sensitivity (from -0.59 +/- 0.10 to -0.30 +/- 0.08 bpm/mmHg). This attenuation was accompanied with an increase in the release of glutamate and glycine from the VLM (+40% and +20%, respectively) at 120 min. Glycine perfusion into this area resulted in an attenuation of baroreflex sensitivity with a magnitude similar to that obtained with infusion of a subpressor dose of ANG II, whereas glutamate perfusion caused a resetting of baroreflex. These results suggest that glycine and glutamate are involved in cardiovascular regulation in the VLM. Furthermore, the augmented releases of these amino acids may account for the underlying mechanism of ANG II-induced attenuation of baroreflex function. PMID- 7882056 TI - Differential clearance of nitroxide MRI contrast agents from rat cerebral ventricles. AB - Seven stable nitroxides have been evaluated as contrast agents in MRI studies of the rat cerebroventricular system. Because the contrast enhancement is primarily confined to the cerebral ventricles, nitroxides can be used to examine the ventricular structure. On the other hand, based on the absence of reducing agents in the rat CSF and on the fact that nitroxides can be reduced intracellularly, the relative reduction in contrast subsequent to an intracerebral injection provides information on the relationship of chemical structure to transmembrane flux in vivo. Observed rate constants and rate constants due to reduction have been analyzed quantitatively by modeling the effects of flow with GdDTPA, which is not subject to reduction. Five-membered ring nitroxides, in general, were reduced at much slower rates than six-membered ring nitroxides. The presence of a positive charge in the structure can substantially slow down the transmembrane flux. PMID- 7882057 TI - Decrease of norepinephrine and preservation of acetylcholine in the hypothalamus of VMH obese rats. AB - We investigated to find which types of neuronal disturbance in the hypothalamus are responsible for ventromedial hypothalamic nucleus (VMH) lesion-induced development of obesity. We found that in VMH-lesioned obese rats, the contents of norepinephrine (NE) and dopamine in the hypothalamus were selectively decreased, but that the serotonin and acetylcholine levels were unchanged from those in sham controls. Also, the content of NE in the lateral portion of the hypothalamus was decreased. Our results show that disturbance of the hypothalamic noradrenergic and dopaminergic neurons, but not of the serotonergic or cholinergic neurons, contributes to the development of VMH lesion-induced obesity. PMID- 7882058 TI - [Redox therapy in mitochondrial diseases using coenzyme Q10]. AB - BACKGROUND: The biochemical and genetic analysis served as the basis for the definition of the following mitochondrial diseases (mt diseases) and the diseases of the mitochondrial deoxyribonucleic acid (mtDNA diseases): mitochondrial myopathy, encephalomyopathy, and cardiomyopathy. The therapy of mitochondrial diseases (in both practice and experiment) belongs to the current trends of research. AIM: The study does not present any new experimental results but in their literary review the authors indicate: a) new trend in biochemical studies of mitochondrial diseases, b) some current knowledge on mtDNA diseases, c) the current trend of mitochondrial disease "redox therapy" by CoQ10, d) significance of the therapeutic task of CoQ10 in four experimental models of the myocardial mitochondria impairment (by ageing, smoking, alcohol, ischemia). SIGNIFICANCE FOR PRACTICE AND RESEARCH DEVELOPMENT: The authors indicate a new perspective for the studies of mitochondrial diseases (mt diseases) and the diseases of the mitochondrial deoxyribonucleic acid (mtDNA diseases) and their therapy not only under experimental conditions, but also in the blood and bioptic samples of patients. (Tab. 3, Fig. 2, Ref. 43.) PMID- 7882059 TI - [The pulmonary surfactant factor. Current knowledge, research trends and use in clinical practice]. AB - Investigation of the composition and significance of individual components of the surfactant indicated that besides phospholipids an important role is played also by surfactant proteins. They aid not only the reduction of the surface tension of the lungs (SP-B, SP-C), but serve also in regulation of surfactant secretion (SP A) and in local defense and immune responses in the lungs (SP-A and SP-D). Impairments of surfactant were discovered not only in RDS, but also in cases of meconium aspiration, congenital diaphragmatic hernia, pneumonia, pulmonary edema, idiopathic fibrosis of the lungs, alveolar proteinosis, pneumothorax, and bronchial asthma. Therapy by means of exogenous surfactant was proved effective in therapy of RDS. Occasional cases of exogenous surfactant therapy in other pulmonary diseases are auspicious, it is necessary, though, to develop and produce a sufficient amount of exogenous surfactant of high quality and at an acceptable price and to find an optimal manner of surfactant administration into the lungs. A significant perspective is anticipated to utilization of intrapulmonary administration of the exogenous surfactant as a carrier of further active substances for local administration into the lungs. (Ref. 36.) PMID- 7882060 TI - [Biochemical and functional study of the liver during treatment of familial hyperlipoproteinemia with Mevacor (lovastatin) and Vasosan S (cholestyramine)]. AB - The aim of our study was the biochemical and functional examination of the liver during the therapy of familiar hyperlipoproteinemia by means of MevacorR (lovostatine) in comparison with the treatment by Vasosan S (cholestyramine). We examined 20 patients treated with a daily dose of MevacorR being 20-40 mg and, 18 patients treated with a daily dose of Vasosan S being 16-32 g for the period of 12 weeks. During the therapy the total cholesterol, LDL-cholesterol, HDL cholesterol, triacylglycerols, hepatic enzymes (AST, ALT, ALP) activity, functional test of the liver, biological half-time of antipyrine (t 1/2 antipyrine) were investigated at the onset and at the end of the study. We discovered that at the end of the treatments by MevacorR and Vasosan S the hypolipidemic effect increased (cholesterol p < 0.001, LDL cholesterol p < 0.001), and there was difference in the effect on HDL-cholesterol and in that on triacylglycerols. During the treatment we discovered that due to both medicaments the liver enzymes activity increased to a different extent. At the beginning of the study the antipyrine biological half-time statistically increased in both investigated groups, namely in comparison with the control group. At the end of the treatments in both groups the antipyrine half-time was prolonged, however not significantly. Prior to long-term therapy by hypolipidemics the authors recommend biochemical and functional examination of the liver. (Tab. 4, Fig. 8, Ref. 7.) PMID- 7882061 TI - [Changes in thrombocyte aggregation in patients with type I diabetes]. AB - The authors present the results of evaluation of platelet aggregation by means of an automated system (on line detection of platelet aggregation curves) in 80 patients with diabetes mellitus type I. After global analysis no significant changes were found between controls, patients without diabetic nephropathy, and patients with incipient and clinically manifested nephropathy. However, as a result of our data, the area below the aggregatory curve is minimal in the group of patients with clinically manifested diabetic nephropathy. Additional changes of platelet aggregation were observed after dividing the followed set of patients dividing into homogenous subgroups according to their sex. The sensitivity of platelets after induction by ADP was found to be lower in male diabetics than in male controls. Likewise the area below the aggregatory curve and the transmittance of absolute maximum of platelet aggregation was lower in female diabetics than in female controls. In both cases diabetic nephropathy could have participated in platelet sensitivity changes. The authors' findings in the followed group of patients when compared with the described platelet hyperaggregability in diabetes approves the possibility of the platelet aggregatory polymorphism being present in these patients. With respect to these findings the examination of the platelet aggregation and its general parameters exactly justifies the usefulness of the antiaggregatory therapy. (Fig. 4, Ref. 15.) PMID- 7882062 TI - [Changes in cholesterol and triacylglycerol serum levels in rats during postnatal ontogenesis]. AB - In the serum of young normal rats during the first two months of life the concentrations of triacylglycerols (TG) and of cholesterol (CH) were determined. Low values in both studied parameters found in newborn animals were followed by a marked increase during the first week of life. In comparison with adult animals high values remained during the first five weeks of life. The results are discussed with regard to the high intake of lipids by milk during the period of sucking, as well as from the point of possible mobilization of tissue lipid stores because of the similar trend in the ontogenetic expression of the gene coding the hormone-sensitive lipase (HSL). On the basis of evaluation of the analytical as well as biological variance it was found, that for the level of 50% of confidentiality the serum concentrations of cholesterol should be in the range X +/- 0.26 mmol/l. For the level of 95% the range of values is X +/- 0.67 mmol/l. It is suggested that these results could be used as reference values for serum lipids in the rat during ontogenesis. (Fig. 1, Ref. 21.) PMID- 7882063 TI - [The effect of chronic acidosis on the activity of renal glutamate decarboxylase and GABA-transaminase]. AB - Chronic acidosis evoked by a 7-day application of ammonium chloride in concentration of 2% increased the activity of glutamate decarboxylase (GAD) in renal homogenates of rats to approximately 160%. The enzyme activators, chlorides and adenosine triphosphate influenced in varying measures the GAD activity in renal homogenates of both controlled and acidotic animals. Whilst ATP was gradually loosing the activating effect, chlorides preserved it. The renal GAD is firmly bound on insoluble structures. The increase in GAD activity due to acidosis was accompanied by increasing permanence of this bind. After the substitution of ammonium chloride by drinking water, the return of the increased GAD activity to previous normal values lasted 7 days, whilst apparent normalization of the weight of experimental animals reoccurred on the first day. Subfractionation of the crude renal mitochondrial fraction by use of enzyme markers localized GAD in mitochondria. In renal homogenates the activities of GABA-transaminases were assessed. GABA-alpha-ketoglutarate transaminase was 5x more active than GABA-pyruvate transaminase. Acidosis resulted in augmentation of both transaminases--the first to 130%, the second to 160%. (Tab. 5, Fig. 3, Ref. 25.) PMID- 7882064 TI - [Adverse effects and side-effects of antimycotic agents]. AB - The study lays emphasis on the significance and actuality of infections, especially in coincidence with immunodeficient states. Candidosis, mycotic diseases caused by moulds, systemic mycoses, and onychomycoses represent the major problems of modern mycology. They require usually a long-term therapy by means of highly active antimycotics. Consequently, an entire series of undesirable side-effects supervene. External applications result most frequently in contact eczemas and therefore often require preventive patch tests. Oral administration results in general hepatic, renal, hematologic and other impairments which require the monitoring of the latter parameters during therapy. Finally a considerable significance is ascribed to interaction with other simultaneously applied drugs with the antimycotics. (Tab. 1, Ref. 83.) PMID- 7882065 TI - [The human spleen in idiopathic thrombocytopenic purpura]. AB - Idiopathic (autoimmune) thrombocytopenic purpura (ITP, AITP) represents a relatively frequent impairment. It involves a syndrome of various diseases with a shortened thrombocytes survival caused by anti-platelet antibodies. The majority of cases are of secondary character. Spleenectomy often evokes a complete remission of thrombocytopenia. The study describes morphologic findings in spleens of 30 patients with the clinical diagnosis of ITP/AITP. The findings were gained by light microscopy from formol-paraffin blocks and histochemical findings from cryostat sections of non-fixed tissue. The alcaline and acidic phosphatases, nonspecific esterase, chloracetate esterase, and dipeptydilpeptidase IV were investigated enzymohistochemically. Immunoglobulins were examined immunohistochemically and T lymphocytes by means of monoclonal antibodies. The affinity HPA--Helix pomatia agglutinin, PHA--phytohemagglutinin from Phaseolus vulgaris, SBA--soy-bean agglutinin from Glycine max. and PSA--peas bean agglutinin from Pisum sativum were investigated by means of specific antilectin antibodies. The human spleen during idiopathic thrombocytopenic purpura accumulates neutrophilic polymorphonuclear granulocytes; platelets-stagnate and are destroyed. These processes can be identified in histologic sections e.g. also by means of anti-fibrinogen antibodies. The red pulp contains foam cells to various extent. Besides generally known processes, the white pulp also displays alterations in composition of cellular compartment of the periarterial lymphatic sheaths. Human spleen distinguishes modified blood platelets as alien corpuscles, and thus eliminates them from the blood circulation system by its immunologic and other mechanisms, the details of which still remain to be clarified. (Fig. 6, Ref. 44.) PMID- 7882066 TI - [The effect of beta-escin on metabolism in experimental liver steatosis in rats]. AB - The aim of the study was to investigate the effect of beta-aescin on the selected indices of sugar and lipid metabolisms in blood and hepatic tissue. The study was performed under the conditions of toxic impairment of the liver caused by carbon tetrachloride or hydrazinsulphate which were used in order to evoke experimentally the steatosis of the liver. The study investigated whether beta aescin can cause deterioration of hepatic steatosis. Carbon tetrachloride was administered to rats by stomach probe in dosis of 2.5 ml per kg of body weight, or hydrazinsulphate in dosis of 2 mmol per kg of body weight, i.m.. Twenty-four hours after administration of these two substances beta-aescin water solution was administered in dosis of 10 mg per kg of body weight by means of stomach probe. The analysis of blood and liver tissue samples discovered that beta-aescin did not affect the metabolic indices, steatosis of the liver did not become more profound. (Tab. 2, Fig. 11, Ref. 23.) PMID- 7882067 TI - [Short-term administration of increasing doses of thyroxine has a different effect on serum lipids in male rats and in female rats]. AB - The effects of short-term administration of thyroxine (T4) on serum levels of cholesterol, HDL-cholesterol and triacylglycerols were studied on young adult rats. T4 was injected in three different doses, i.e. 125, 250 and 500 micrograms for four days. The results show significant sexual differences. T4 caused a significant decrease in HDL-cholesterol levels in both sexes. The concentration of cholesterol and triacylglycerol decreased only in males, namely after injections of the highest dose of T4. In females the T4 injections caused no effect in the investigated parameters. It is concluded, that also in short-term applications of hormones, the sex may significantly change the results. Presented results support the latest views on specific interrelationship between thyroid hormone and HDL in comparison with other types of LP. (Tab. 2, Ref. 16.). PMID- 7882068 TI - [Legionellosis in Slovakia]. AB - According the European Working Group on Legionella Infections the disease continues to occur sporadically or in small outbreaks, usually in connections with the survival of legionellae in hot water supply systems. It appears mostly as a nosocomial infection or as a travel associated disease. The introduction of laboratory diagnostic methods allowed us to approach this problem in our country. Detection of anti-legionella antibodies in the serum was performed by means of microagglutination and indirect immunofluorescence reaction. During 1985-1994 twenty-one sporadic cases, mostly pneumonias, could be diagnosed. As etiologic agents L. pneumophila 4, 12, 3, 2 and 1 besides legionella-like organisms L. bozemanii and less often L. micdadei and L. dumoffii were determined. In contrast to the general believe that mostly L. pneumophila 1 is involved in human cases, in our group of patients other serologic groups of L. p. and other species of legionellas were involved. The limited number of investigations does not allow us a real picture on the occurrence of legionelloses and their etiological structure in our country. It is expect that the widening of diagnostic examinations and an increased interest of clinicians to clarify etiologically acute suspect infections will contribute to a better knowledge of the medical importance of this disease. (Tab. 1, Ref. 15.). PMID- 7882069 TI - [CT and MR imaging in stereotaxic neurosurgery]. AB - The combination of CT and MR examinations indicates a specific approach to the treatment of brain mass lesions. CT guided stereotaxy is sufficient for well demarcated tumors, haemorrhages and abscesses. MR guided stereotaxy is necessary to be performed in invasively growing brain tumors where explicit histological verification and localisation must be ascertained. In addition it is necessary to take into account the image deformation due to the stereotactic ring. In functional neurosurgery the MR examination visualises the anatomical structures which are needed for the ascertainment of coordinate systems landmarks in coordinate system. (Fig. 1, Tab. 1, Ref. 5.). PMID- 7882070 TI - [Familial epidemics of tick-borne encephalitis in central Povazie]. AB - The authors describe two cases of tick-born encephalitis family epidemies in the natural focus of tick-born encephalitis (TbE) in the central part of Povazie in the district of Povazka Bystrica in the years 1989 and 1993. The infection took place due to consumption of raw goat milk. The best prevention against tick-born encephalitis is represented by vaccination. (Tab. 4, Ref. 6.) PMID- 7882071 TI - [Validity of the Brief Psychiatric Rating Scale]. AB - The internal structure and validity of terms used in the Brief Psychiatric Rating Scale (Overall and Gorham, 1962) was analyzed. The data which had been gained at the entrance examination of 1557 inpatients with the diagnosis according to ICD-9 (schizophrenia simplex, schizophrenia paranoids, schizoaffective disease depressive type, schizoaffective disease manic type, manic-depressive disease manic phase, manic-depressive disease depressive phase) were processed using stepwise discriminant analysis (SDA). Three-dimensional space defined by SDA provided a sufficient frame of relations for the majority of diagnostic groups. Incomplete component analysis justified the assumption of a relatively stabile internal structure of the method. The findings allow to recommend the Czech version of the scale for the purpose of description of psychic impairments in psychiatry. PMID- 7882072 TI - [Specialized data bases in Slovak library-information centers]. PMID- 7882073 TI - Frontobasal approach for trauma and tumor. AB - The potential for remediation of a host of varied disease processes afflicting the skull base has been increasingly realized over the past two decades. Advances in medical technology, the development of new approaches, and most importantly the close cooperation of the head and neck surgeon and the neurological surgeon have made this possible. Surgeons are attempting to diminish the injury to normal un-involved structures while at the same time maximizing exposure and enabling rectification of the disease or disorder. This is especially pertinent in a number of frontobasal approaches used in anterior craniofacial surgery. The osteoplastic flap approach to the posterior wall of the frontal sinus to repair small cerebrospinal fluid leaks and manage posterior wall fractures saves the patient a larger anterior craniotomy and brain retraction. Cranialization of the frontal sinus in comminuted through-and-through fractures allows for removal of devitalized brain, dural repair, and safe management of the frontal sinus. The lateral rhinotomy medial maxillectomy-ethmosphenoidectomy approach coupled with either an osteoplastic flap of the frontal sinus or a low limited craniotomy is an excellent approach for resection of tumors encroaching on the anterior skull base. Even malignancies of this region can be completely excised with adequate margins, yet produce minimal to no facial aesthetic distortion. Moreover, larger tumors requiring a more extensive lip-splitting incision and total maxillectomy with orbital exenteration can often anticipate minimal deformity, especially with good prosthetic rehabilitation. In the resection of aggressive malignancies, techniques of ocular preservation and facial bone sparing have been developed with encouraging cosmetic results. PMID- 7882074 TI - Endoscopic fenestration of the 3rd ventricular floor in aqueductal stenosis. AB - Six endoscopic fenestrations of the 3rd ventricular floor have been performed in patients with stenosis (SAS) of the aqueduct of Sylvius in our institute during the last two years. The endoscopic intraventricular landmarks were the Monro's foramen followed by the mamillary bodies. The fenestration instrument was a monopolar coagulation wire, the dilatation instrument was a balloon catheter. The patients included two newborns and four adults. The two newborns developed a recurrent hydrocephalus after 2 months. The four adults remained well after the operation. The only complication was edema (SIADH syndrome) in one case for 24 hours. Flow sensitised phase MRI showed a mirroring in the prestenotic CSF pulsation curve preoperatively. This, in combination with an increased intraventricular pulsation, is a sign of reduced capacity of the subarachnoid space at the cerebral surface. The postoperative patency of the fenestration with diminished intraventricular pulsation can be demonstrated with ECG retrogated phase MRI. There was a slow and incomplete decrease of the preoperative enlarged ventricular size. This operative method is a low-risk, minimal invasive alternative method to shunt implantation in adults with SAS. PMID- 7882076 TI - Intraoperative fusion of field images with CT/MRI data by means of a stereotactic mechanical arm. AB - In this paper we describe a neurosurgical articulated arm used as a pointer and as a support for intraoperative image acquisition, integrated with a graphic 3-D rendering system. The patient's anatomy is volumetrically displayed, from stereotactically acquired CT, MRI, and DSA images; the head holder is the common reference system for image reconstruction and for the calibration of the surgical arm. Arm orientation in stereotatic space is displayed, together with the surgical arm. Arm orientation in stereotatic space is displayed, together with the volumetric reconstruction of cerebral lesions and surrounding healthy tissue. The arm, equipped with fail-safe electromagnetic brakes, can be employed to support imaging sources such as an endoscope, an echographic probe, or a CCD camera, whose images can be stereotactically integrated with preoperative data in performing minimally invasive neurosurgical procedures. PMID- 7882075 TI - Oblique transcorporeal drilling to treat anterior compression of the spinal cord at the cervical level. AB - Oblique transcorporeal drilling is a new surgical technique in which the transverse foramina with the vertebral artery and lateral aspects of the bodies of the cervical vertebrae are exposed; it allows to drill out obliquely from the antero-lateral to the opposite postero-lateral corner, half of one or several cervical vertebral bodies. The technique is shortly described and its indications are discussed. It can mainly be applied to release osteophytic compression and to remove anteriorly developed tumors. The advantages are to work in a wide field with all important structures kept medially and protected and to keep a sufficient portion of the vertebral bodies to preserve the spine stability. This technique has been used in 39 cases with spondylosis in 27 cases, tumor in 11 cases and kyphosis in 2 cases including one with neurofibroma. Results in term of decompression were excellent in all cases. Mortality was none and morbidity was limited to a transient Horner's syndrome in almost all cases and to a CSF leak in three cases. This technique is therefore alternative to the anterior transcorporeal approach. In our experience, the oblique transcorporeal drilling provides a wider and safer access to lesions located anterior to the spinal cord. PMID- 7882077 TI - Angioscopy-guided placement of balloon-expandable stents in the treatment of experimental carotid aneurysms. AB - This study was designed to assess the efficacy of a metallic, rigid, balloon expandable stent (Palmaz-Schatz) for occlusion of an aneurysm. First, a glass model of two types of aneurysms was constructed, one simple lateral aneurysm and one lateral aneurysm with a side branch. After placement of the stent, the flow towards the distal, post-aneurysmal part of the glass tube was increased with immediate reduction of the flow towards the aneurysm. Beside some turbulences around the struts of the stent there was some inflow of dye into the aneurysm with partial and delayed filling of the aneurysm and delayed washout of the dye from the aneurysm. The same observations could be made with the side-branch aneurysm model. Although parts of the struts involved the ostium of the side branch, there was no flow alteration towards this branch. Second, 10 experimentally constructed aneurysms of the carotid artery in beagles were treated with stents. These stents were placed transfemorally and, since the stents were barely visible under fluoroscopy, angioscopy was performed before and after stenting in order to improve positioning of the stent. In 8 out of 10 cases placement of the stent resulted in an immediate complete occlusion of the aneurysm with remaining patency of the carotid artery. In the other 2 cases, a delayed, but complete occlusion was achieved. In one case, the carotid artery was completely occluded at a follow-up angiography after two weeks, probably induced by intimal damage during insertion of the stent. In two other cases, there was considerable stenosis of the carotid artery due to intimal proliferation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882078 TI - Minimally invasive stereotaxy: clinical use of the Gill-Thomas-Cosman (GTC) repeat stereotactic localiser. AB - The Gill-Thomas-Cosman (GTC) repeat stereotactic localiser allows frame-based stereotaxy to be performed in a minimally invasive manner by using dental fixation rather than traditional skull pins. The GTC enables accurate relocation in the same stereotactic space so that image acquisition and surgery can be separated if necessary. The device is especially suitable for fractionated stereotactic radiotherapy where it conveniently provides both patient-frame and frame-couch fixation on a repeatable basis. PMID- 7882079 TI - The thorny road to minimally invasive techniques in neurosurgery. AB - This article is a brief personal account of a neurosurgeon who started his career in 1950. In spite of the subjective nature, this paper also attempts to provide some objective evidence to the history of our specialty. The terrible pain causing pneumoencephalography and percutaneous carotid angiography, indispensable of the neurosurgery yesterday, seem to be a nightmare even for a physician today. The psychological stress of a patient at a brain operation in local anaesthesia was enormous, not to speak about the vegetative instability inherent with this anaesthesiological modality. The technical and scientific progress in the last decades, the modern diagnostic methods, the introduction of microsurgical technique and the modern anaesthetical methods and intensive care brought about an important change in the strategy and tactical considerations of neurosurgical interventions. Today the aim of our operations is not only to save life, but to improve the quality of life of the patient. Our surgical policy is directed by the knowledge of microscopical anatomy, the knowledge of arachnoidal membranes and cisterns and the introduction of microneurosurgical techniques. PMID- 7882080 TI - The year of learning. PMID- 7882081 TI - The class of '93.... PMID- 7882082 TI - HIV and AIDS: a family approach to care. PMID- 7882083 TI - An analysis of family care. PMID- 7882084 TI - The process of normalisation in children with chronic illness. PMID- 7882085 TI - Asthma in children. PMID- 7882086 TI - HIV and AIDS: when care is for the whole family. PMID- 7882087 TI - Community nursing. Widening the gate. PMID- 7882088 TI - Limb deficiencies. Help within reach.... PMID- 7882090 TI - Using existing measurement instruments. PMID- 7882089 TI - Symptom Questionnaire anxiety and depression scales: reliability and validity. AB - Many instruments have been developed with college students and used primarily with students or younger adults. Thus, researchers face challenges in selecting measures of psychological state that are valid and reliable for use with elders. This article describes a measure of psychological state, the Symptom Questionnaire; provides information about its reliability and validity; and details the steps used to evaluate reliability and validity of its anxiety and depression scales for elders hospitalized for an acute episode of a chronic condition. The findings suggest that a short version of the Symptom Questionnaire, consisting of the depression and anxiety scales, is valid and reliable for elders. The findings also revealed small differences between the means of data collected using the short version and those obtained using the full instrument. PMID- 7882091 TI - Reliability of aggregated organizational data: an evaluation of five empirical indices. AB - Nursing systems research has included many levels of measurement such as individuals, work groups, organizations, and systems of organizations. Variables important to organizational survival often are measured at the individual level, with inferences made to the work group or the organization. This study demonstrated a process for determining the reliability of individual level data aggregated to the work group and organization levels. Data were analyzed on four variables: job enjoyment; manager's leadership style in terms of structuring expectations and consideration; and control over nursing practice. Job enjoyment was assessed over time. Registered staff nurses (n = 632), representing 54 nursing units from 4 large acute care hospitals, comprised the sample. The results indicated the assessment of reliability and validity is important at the level of inference and at each time interval. Aggregated data were deemed reliable when the following criteria were met: Cronbach's alpha > .60; intraclass correlation (1,k) > .60; and a significant F ratio. The interpretation of omega 2 as an indicator of effect size suggested that the validity of inference at the aggregated level is in question when effect size is negligible or small. PMID- 7882092 TI - Using generalizability theory for the estimation of reliability of a patient classification system. AB - This article discusses the measurement issues associated with estimating the reliability of patient classification systems (PCSs). Generalizability theory is proposed as an approach to overcome the limitations of traditional methods of estimating reliability of PCSs. The results of a demonstration study in which generalizability theory is used to support the reliability of a PCS are reported. A coefficient of generalizability, analogous to the reliability coefficient, was computed based on the variance components estimated. The generalizability coefficient for the total PCS score was .034, which increased to .650 when one item was deleted. The generalizability coefficient for individual items ranged from .053 to .961. Suggestions for further instrument development are offered. PMID- 7882093 TI - The Interpersonal Relationship Inventory: continued psychometric evaluation. AB - For norm-referenced measures to be useful in social-behavioral research, investigators who develop measures face several psychometric challenges, including: (a) adequate domain specification; (b) adequate initial evidence of reliability and validity; and (c) ongoing evidence of psychometric quality. The Interpersonal Relationship Inventory (IPRI) was developed in response to gaps in measurement of social relationships, and contributed scales for reciprocity and conflict to a measure of social support. For the IPRI, the first two points were addressed during the period of instrument development. The measure now has been in use for 4 years. This article reports evidence addressing the third challenge: ongoing evidence of psychometric quality. Findings from 19 studies using the IPRI provide compelling evidence for internal consistency reliability and construct validity of the scales. PMID- 7882094 TI - Development of an observational instrument to study nurse-patient touch. AB - A detailed analysis of videotaped data of nurse-patient interactions (NPIs) was used to identify the structure of NPIs and the important behaviors comprising touching interactions that could serve as a basis for the development of an observational instrument to study nurse-patient touch. The resulting coding system enabled observers to record types of nurse attending, eye gaze, proximity, nurse-patient dialogue, nurse activity, patient condition, presence of others in the room, and characteristics of nurse-patient touch. To evaluate this instrument, two samples of videotaped NPIs were selected and coded by three observers. Acceptable levels of interobserver and intraobserver agreement and observer reliability were established and maintained throughout the coding process, with the exception of two categories (i.e., nurse activity and intensity of touch). The two samples were compared to provide further support for the content validity of the coding system and to evaluate the sensitivity of the measure to the same behaviors in different samples of NPIs. It was concluded that this instrument has potential for use in describing the patterns of touch nurses use in a more comprehensive and detailed way than has been done in the past and that this instrument warrants further study in other clinical contexts. PMID- 7882095 TI - Issues regarding aggregation of data in nursing systems research. AB - The unit of analysis at which variables are conceptualized and measured is an important consideration when conducting patient outcomes research. Outcomes research ranges from study of individual responses to nursing intervention to investigation of group level outcomes associated with the contexts and processes through which nursing care is delivered. Because many variables salient to the investigation of group level patient outcomes are not amenable to direct measurement, aggregation procedures are used to generate proxy measurement of organizational context or process variables. In this article, key conceptual and methodologic issues encountered when using data aggregation procedures are reviewed. Following this, estimation of aggregated data reliability is illustrated using data from a study conducted to investigate skilled nursing unit structures. PMID- 7882096 TI - Localized or systemic in vivo heat inactivation of human immunodeficiency virus (HIV): a mathematical analysis. AB - Temperatures > or = 42 degrees C, maintained for > or = 25 min, inactivate approximately 25% of human immunodeficiency virus (HIV). HIV-infected T cells are more sensitive to heat than healthy lymphocytes, and susceptibility increases when the cells are presensitized by exposure to tumor necrosis factor. Thus, induction of a whole-body hyperthermia or hyperthermia specifically limited to tissues having a high viral load is a potential antiviral therapy for acquired immunodeficiency syndrome (AIDS). Accordingly, we incorporated therapeutic hyperthermia into an existing mathematical model that evaluates the interaction between HIV and CD4+ T cells. Given the assumptions and limitations of this model, the results indicate that a daily therapy lowering the population of actively infected cells by 40% or infectious virus by 40% would effectively reverse the depletion of T cells. In contrast, a daily decline of 20% of either actively infected cells or infectious virus would have a marginal effect. However, daily reduction by 20% of both actively infected cells and infectious virus could restore T-cell numbers, assuming that permanent damage had not been inflicted on the thymus. Since daily treatments would probably be excessively stressful, whole-body hyperthermia seems unlikely to be clinically useful. In contrast, heating directed specifically to areas of viral concentration may be effective and have a suitable risk/benefit ratio. PMID- 7882097 TI - Functional analysis of the vpx, vpr, and nef genes of simian immunodeficiency virus. AB - The role of the vpx, vpr, and nef genes in the replication of simian immunodeficiency virus (SIV) was investigated using point and deletion mutations in these genes. The effects on replication kinetics of single or combined mutants -vpx, vpr, vpx-vpr, vpx-nef, vpr-nef, and vpx-vpr-nef--in established lymphoid CEMx174 and MT-4 cells were negligible, except that the postinfection appearance of vpx-nef, vpr-nef, and vpx-vpr-nef progeny virus was slightly delayed in MT-4 cells. The vpx, but not the vpr, point mutation reverted to wild-type sequences within 12 days after infection, suggesting that stronger selection pressure for Vpx than for Vpr expression might exist in these established cell lines. In contrast to growth in the lymphoid cell lines, replication of vpx-deleted viruses in macaque peripheral blood mononuclear cells (PBMC) was severely impaired, indicating that Vpx is necessary for efficient replication in PBMC. In contrast, the vpr mutant exhibited different degrees of impairment depending on the donor animal used as a source of PBMC. A virus encoding a Vpx-Vpr fusion protein replicated in PBMC comparably to a vpr deletion mutant virus, whereas a frameshift deletion at the vpx-vpr junction of this mutant eliminated virus replication, suggesting that deletion of the C-terminal half of Vpx was partially compensated by the presence of the large Vpr portion in the fusion protein. Deletion of the nef gene did not affect SIVmac replication in PBMC. The Vpx and Vpr proteins expressed in COS-1 cells were detected in the extracellular medium and did not crossreact with Vpr- and Vpx-specific antisera, in spite of extensive amino acid similarity between these proteins. These studies indicate the importance of Vpx and Vpr in SIVmac infection and suggest that these proteins are antigenically and functionally distinct. PMID- 7882098 TI - Reconsidering the use of adjunctive corticosteroids in Pneumocystis pneumonia? PMID- 7882099 TI - A multicenter randomized double-blind placebo-controlled trial of adjunctive corticosteroids in the treatment of Pneumocystis carinii pneumonia complicating the acquired immune deficiency syndrome. AB - A multicenter placebo-controlled trial of early short-term high-dose methylprednisolone enrolled 78 patients with moderate to severe Pneumocystis carinii pneumonia (PCP) complicating HIV infection. The mean pressure of oxygen (PO2) at study entry was 55 mm Hg for the 71 patients who had blood gases monitored while breathing room air. Patients were randomized to receive methylprednisolone (40 mg) or placebo parenterally twice daily for 10 days, and the first dose of study medication was given within 24 h of the first dose of antimicrobial therapy for PCP. The primary end point included death, need for mechanical ventilation for > 6 days, or a partial PO2 < 70 mm Hg while breathing room air 10 days after initiation of treatment. There was no statistically significant difference in the primary end point between patients randomized to corticosteroid (CS) or placebo (PL) (p = 0.522; 95% CI = -0.30, 0.16). The incidence of superinfections during therapy or of other HIV-associated infections or malignancies in the 6 months following treatment for PCP was not significantly different between the two groups. More patients randomized to placebo had to discontinue treatment with trimethoprim-sulfamethoxazole because of hypersensitivity than those randomized to corticosteroids (p = 0.039). We conclude that addition of corticosteroids does not significantly affect the outcome of PCP in patients with HIV and a PO2 < 70 mm Hg on room air at presentation but lowers the incidence of hypersensitivity reactions to trimethoprim-sulfamethoxazole. PMID- 7882100 TI - Early and prolonged decrease of viremia in HIV-1-infected patients treated with didanosine. AB - Fourteen patients previously treated with zidovudine were monitored for laboratory parameters and clinical events during 1 year after introduction of didanosine (ddI) monotherapy. Proviral human immunodeficiency virus type 1 (HIV 1) copy numbers (cell-associated DNA) and concentration of free virions (viremia) were determined using a semiquantitative polymerase chain reaction (PCR). High levels of circulating virus were detected in all patients (range, 17 to 5,934 x 10(3)/ml of serum). Within 4 weeks of therapy, a decrease of viremia (60 to 98%) was observed in nine patients. After 1 year of treatment, eight of these nine patients still had decreased viremia when proviral HIV DNA was decreased or stable, and CD4+ lymphocytes were stable or higher in seven of these eight patients. Antiviral effect was more pronounced in the six patients with CD4+ > 100/mm3 at entry, five of them belonging to the subgroup of the seven responding patients as compared to two of eight patients with CD4+ < 100/mm3. Clinical events in this small group were not statistically correlated with virologic parameters; however, responding patients had a tendency to stabilize or gain weight. This study suggests that measurement of viremia deserves further study as a marker of antiviral efficacy and might predict, even at 4 weeks, the beneficial potential of ddI. PMID- 7882101 TI - Hospital admissions of HIV-infected patients from 1988 to 1992 in Maryland. AB - To determine how the patterns of inpatient hospital care for HIV-infected patients have evolved in recent years, we analyzed data obtained from a statewide hospital discharge database from Maryland for the years 1988, 1990, and 1992. For each of these years, we compared demography, diagnoses, lengths of stay, use of the intensive care unit, third-party payer, and hospital charges (inflation adjusted to 1992 dollars). HIV-infected patients accounted for 0.42% of all Maryland's hospital admissions in 1988, 0.68% in 1990, and 1.1% in 1992, with progressively more women and African-Americans hospitalized. Average lengths of stay fell from 11.7 days (1988) to 10.7 days (1990) and 9.5 days (1992) (p < 0.0001). Average charges per admission fell from $11,634 (1988) to $9,938 (1990) and $8,618 (1992) (p < 0.0001). Medicare or Medicaid paid for 50.9% of hospital admissions in 1988, 56.8% in 1990, and 66.8% in 1992 (p < 0.001). In-hospital mortality rates (7.8% in 1988, 7.9% in 1990, and 7.7% in 1992; p = 0.783) were stable, as was severity of illness. P. carinii pneumonia (PCP) was the most common principal diagnosis, but it declined in prevalence from 13.6% in 1988 to 9.1% in 1992 (p < 0.0001). Principal diagnoses of other opportunistic infections remained stable (8.0% in 1988, 9.9% in 1990, 8.6% in 1992; p = 0.90), as did other nonopportunistic infections (32.8% in 1988, 27.2% in 1990, and 30.0% in 1992; p = 0.16). Non-PCP pneumonias increased from 7.6% (1988) to 10.2% (1992) (p < 0.0001). Substance abuse as a principal or secondary diagnosis increased from 30.9% (1988) to 34.3% (1992) (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882102 TI - The learning curve for AIDS-related Pneumocystis carinii pneumonia: experience from 3,981 cases in Veterans Affairs Hospitals 1987-1991. AB - Previous studies have found lower mortality rates for AIDS-related Pneumocystis carinii pneumonia (PCP) in hospitals with higher levels of experience with PCP. It is not known if patients are selectively referred to better hospitals or if there is a learning curve whereby outcomes improve as physicians gain experience in treating PCP. We assessed cases of PCP at 140 Veterans Administration (VA) Medical Centers in the United States. During 1987-1991, 3,981 patients were hospitalized with first-episode AIDS-related PCP. Mortality at 30 days after admission. For these 3,981 hospitalizations at the 140 study hospitals, the 30 day mortality was 19%. Logistic regression models indicate that older age, race, geographic area, earlier year of treatment, hospitalization in the previous 12 months, and lower levels of hospital experience with AIDS were significant predictors of mortality at 30 days after admission. Compared with hospitals that had treated three cases or fewer of first-episode PCP, the odds of mortality at 30 days at hospitals that treated > 50 cases of first-episode PCP were 0.73 (95% confidence interval 0.58-0.91), after controlling for differences in characteristics of the patients, year, and region. Mortality of patients with AIDS-related PCP decreases as VA hospitals gain experience. Longitudinal analyses over a 5-year period suggest that a learning curve best explains this finding. PMID- 7882103 TI - Identification of a clonal form of HIV in early Kaposi's sarcoma: evidence for a novel model of oncogenesis, "sequential neoplasia". AB - We recently reported clonal human immunodeficiency virus (HIV involvement in four acquired immune deficiency syndrome (AIDS)-associated non-B-cell lymphoproliferations. In three of these cases HIV expression was localized to tumor-associated macrophages. Because one of the cases had a major component involved in angioproliferation, we speculated that some form of Kaposi's sarcoma (KS), which also has a major component of angioproliferation, might be involved clonally with HIV. The current study is an evaluation of four cases of KS and control tissues taken from four patients who died with complications of HIV disease. With use of the inverse polymerase chain reaction technique to identify clonal forms of HIV, a clonal form of HIV was found in one of four KS cases. The HIV-positive tumor was an early KS lesion of the bowel, and uninvolved bowel from the same patient showed no clonal HIV. Immunohistochemical analysis demonstrated the presence of prominent HIV-expressing macrophages that also coexpressed high levels of HIV tat, basic fibroblast growth factor, and interleukin-6. These data provide evidence for a pathogenic process termed "sequential neoplasia," wherein a clonal macrophage provides a growth factor milieu stimulating the proliferation of a responder cell population that ultimately becomes autonomous. In the current case, the macrophages expressing HIV were located adjacent to the KS tumor tissue and were found to be producing known KS growth factors. The absence of finding clonal HIV in three more advanced KS lesions suggests that the clonal macrophage may be required only for early pathogenesis and that sequential neoplastic changes occurring in the endothelial cells gave rise to autonomous KS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882105 TI - Potential and actual workdays lost among patients with HIV. AB - How many more potential and actual workdays are lost by HIV patients than persons without HIV? To answer this question, we assessed differences in the number of workdays among a panel of AIDS patients, patients who were HIV positive but did not yet have AIDS, and comparison patients. The patients included persons who were employed and unemployed. Information on 1,346 patients was gathered from January 1, 1990, to December 31, 1992, as part of the ongoing ATHOS (AIDS Time Oriented Health Outcome Study) study. Data were collected every 3 months on AIDS and HIV-positive patients and every 6-12 months on the comparison patients. At the end of the study (December 31, 1992), 856 people were still enrolled. A total of 5,507 panel data points covering 3 years were available. Data were analyzed with a linear regression model. We found that patients with AIDS reported 29-32 and HIV-positive patients reported 9-13 more potential and actual workdays lost out of the previous 90 than the comparison patients, other variables being equal. All p values were < 0.005, and most were < 0.0001. We conclude that (a) while the AIDS patients showed substantially more workdays lost than the comparison group, the HIV-positive group showed only a modest number of more days lost than the comparison group and (b) that previous estimates exaggerated indirect morbidity costs. PMID- 7882104 TI - CD4+ lymphocyte count in African patients co-infected with HIV and tuberculosis. AB - The objectives of this study were (a) to compare the CD4+ lymphocyte profiles over time of two groups of patients hospitalized for tuberculosis (TB) treatment [a group of patients with TB only (TB group) and a group dually infected by HIV and TB (HIV/TB group)] and (b) to assess the usefulness of the total lymphocyte count (TLC) as a surrogate of the CD4+ lymphocyte count in the HIV/TB group. A total of 345 patients were enrolled in the study of whom 104 (29.8%) were HIV seropositive (HIV/TB). On admission, the CD4+ lymphocyte counts of the HIV/TB cohort were significantly lower than the TB group with medians of 230 (interquartile range, 90-475) and 630 (500-865), respectively (p < 0.0001). The CD4+ lymphocyte count increased significantly in both cohorts on routine TB treatment. A TLC of 1,300-1,500 cells/mm3 was found to be predictive of a CD4+ lymphocyte count of < or = 200 cells/mm3 both on admission and after 1 month of TB therapy. We conclude from this study that the positive influence of TB therapy on the CD4+ lymphocyte count strongly suggests an additional avenue of influence on the course of HIV infection, whereas the usefulness of the TLC as a surrogate estimation of CD4+ lymphocyte count in HIV/TB patients has important implications for the developing world. PMID- 7882106 TI - HIV in injecting drug users in Edinburgh: prevalence and correlates. AB - A citywide sample of injecting drug users (IDUs) who had injected in the previous 6 months was recruited in Edinburgh. Interviewers administered a questionnaire enquiring about drug use, sharing of injecting equipment, sexual behavior, and imprisonment. A specimen of saliva was assayed for human immunodeficiency virus (HIV) IgG. HIV antibody prevalence in 346 IDUs recruited between June 1992 and October 1993 was 19.7% (95% confidence limits, 15.5 and 23.9%). Univariate analyses indicated that infection was significantly associated with being 27 to 36 years of age, starting to inject between 1975 and 1980, injecting in 1980-1987 and, particularly, 1982-1984, injecting in more than 7 years since 1979, reusing injecting equipment already used by another IDU in 1980-1987, being imprisoned, using equipment used by a fellow prisoner, and residing in north Edinburgh. Multivariate analysis showed that being 27-36 years of age, injecting in 1982 1984, and being imprisoned were independently related to being HIV positive. The risk of being infected increased with the number of times of imprisonment. A quarter of the sample said that they had used injecting equipment already used by another person in the 6 months before interview, and 70% said that they had ever done so. Of IDUs who started injecting after 1986, 4.5% were HIV positive. These findings suggest that the potential for HIV transmission by contaminated equipment still exists in Edinburgh. This is particularly so in prison, where IDUs do not have access to new needles and syringes. PMID- 7882107 TI - Comparison of partner notification at anonymous and confidential HIV test sites in Colorado. AB - We compared health department-initiated partner notification at a single anonymous human immunodeficiency virus (HIV) test site in Denver to 13 confidential HIV test sites throughout Colorado over an 18-month period. The average number of named, notified, and counseled in-state partners was from 30 to 50% greater among confidential site index cases than anonymous site index cases, and the seropositivity rate in newly tested partners of confidential site index cases was more than twice the rate in partners of anonymous test site index cases. When analyses were restricted to gay/bisexual male index cases, the results were the same as for the total group. We recommend that state and local health departments collect data to evaluate and improve the delivery of partner notification services. PMID- 7882108 TI - Multisite evaluation of four anti-HIV-1/HIV-2 enzyme immunoassays. Australian HIV Test Evaluation Group. AB - The performance of four enzyme immunoassays, manufactured by Abbott, Diagnostics Pasteur, Genetic Systems, and Organon Teknika, for the combined detection of anti human immunodeficiency virus type 1 (HIV-1) and anti-HIV-2, was examined in a multisite evaluation. The collaborative efforts of 7 Australian Red Cross Blood Transfusion and 12 Australian Public Health Laboratories minimized potential biases in data by providing large numbers of anti-HIV-1-negative and -positive samples. Sensitivity was estimated using samples that were positive for anti-HIV 1 from individuals known to be infected and seroconversion samples. Sensitivity estimates in the four assays were 99.71, 99.94, 99.49, and 99.68%, respectively. Specificity was measured using fresh, sequential blood donations and samples with previous false-positive reactions in other assays. Specificity estimates from blood donations were 99.92, 99.46, 99.67, and 99.85%, respectively. The data were analyzed further using the delta statistic, which distinguishes the performance of assays of similar sensitivity and specificity by providing a measure of how well results in a population of positive or negative samples are removed from the assay's cutoff value. PMID- 7882109 TI - Risk factors for maternal HTLV-I infection in French Guiana: high HTLV-I prevalence in the Noir Marron population. AB - The aim of this study was to compare rates of human T-cell lymphotropic virus type I (HTLV-I) seroprevalence in pregnant women belonging to different ethnic groups in French Guiana and to determine the risk factors associated with HTLV-I seropositivity. All 1,873 deliveries between 1 July 1991 and 30 June 1993 in the only gynecologic and obstetric unit at Saint Laurent du Maroni were enrolled. Serologic status could be established for 1,727 women, with 75 (4.3%) being HTLV I seropositive. The HTLV-I seroprevalence rate differed significantly between ethnic groups: 5.7% for Noir-Marron (70/1,302), 6.3% for Haitian (3/50), and 0% for Creole (126), Amerindians (166), and Hmong (64). In Noir-Marron pregnant women, HTLV-I seropositivity was associated with a maternal age of > 35 years [odds ratio (OR), 3.3; 95% confidence interval (CI), 1.4-7.6], prior miscarriage (OR, 1.7; CI, 1-2.8), prior cesarean section (OR, 2.1; CI, 1.1-4.0), a parity > 4 (OR, 4.0; CI, 1.8-8.8), a gravidity > 6 (OR, 4.2; CI, 2.0-7.2), and a negative Rhesus factor (OR, 2.2; CI, 1.1-4.5). Two separate stepwise logistic regressions were done because gravidity and parity were highly correlated. HTLV-I seropositivity remained associated with a gravidity > 6 (OR, 3.9; CI, 2.1-7.4) and a negative Rhesus factor (OR, 2.6; CI, 1.2-5.3) for the first model and with a parity > 4 (OR, 4.1; CI, 1.9-9.0) and a negative Rhesus factor (OR, 2.5; CI, 1.2-5.1) for the second model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882110 TI - Effects of exercise modality on metabolic rate and body composition. AB - This study was designed to investigate the effects of exercise as a strategy for weight management in overweight women. Specifically, the effects of exercise modality on resting energy expenditure (REE) and body composition [sum of skinfolds and fat-free mass (FFM)] were examined. Participants included 41 overweight, sedentary women aged 25-49 years who had a defined history of dieting. Experimental (n = 26) and control (n = 15) participants were recruited separately. Participants in the experimental group were randomly assigned to either an endurance- or a resistance-training exercise class. Exercise classes designed for a sedentary population were scheduled three times per week for a duration of 3 months. Results indicated that exercise modality had no effect on REE. Exercise, regardless of modality, had a significant effect on body composition (p = 0.0001) as shown by a significant decrease in the sum of skinfolds for the two exercise groups relative to the control group (p < 0.0001). No differences in fat-free mass were observed between groups. Regardless of modality, exercise also resulted in an increased estimated maximum oxygen uptake (VO2max), based on a 1-mile walking test (p = 0.012). The pattern of weight change of the groups was different (p = 0.029) over the 3-month period. Whereas the exercise groups maintained their weight, the control group gained weight (approximately 2.5 kg). Thus, although exercise modality had no effect, the benefits of exercise per se, such as decreased body fat, increased fitness level, and weight maintenance, were observed in this population. PMID- 7882111 TI - Anabolic steroid use by adolescents: prevalence, motives, and knowledge of risks. AB - Athletes and nonathletes use anabolic-androgenic steroids (AAS) to improve their strength and enhance their appearance. Few studies have been undertaken in the 1990s to assess the use of AAS in adolescents, following changes in legislation. This study was conducted to determine the prevalence of AAS use by high school students in Denver, Colorado, an area with high sports participation. A confidential questionnaire was completed by 6,930 students (response rate 96.6%) at 10 Denver high schools. The prevalence of AAS use was 2.7% (4.0% for boys and 1.3% for girls). Prevalence was slightly higher in sport participants than nonparticipants. The mean age of starting AAS was 14 years (range 8-17 years). This study is the first documented detailed assessment of high school students' knowledge of the risks of AAS. It shows knowledge deficits regarding potential side effects. Users of AAS were less likely than nonusers to acknowledge the risks of AAS. Only 18% of students claim to have been informed about AAS by physicians. The results suggest that health care providers should provide more information to adolescents about AAS. If educational efforts are found effective, teaching efforts regarding AAS should start in junior high school or sooner and continue through high school. PMID- 7882113 TI - Dehydration during exercise: what are the real dangers? AB - The belief that dehydration poses significant health risks for endurance athletes, especially marathon and ultramarathon runners, stems from the classical 1969 study of Wyndham and Strydom entitled "The Danger of an Inadequate Water Intake During Marathon Running." The subsequent influence of the paper relates more to its incorrect title than to its scientific content. For the authors did not study nor did they identify any dangers resulting from an inadequate water intake during marathon running. In fact, the most dehydrated runners in their studies were also the most successful, as they won the competitive races that were studied. The positive result of the study was to influence international rule changes to allow increased fluid intake during competitive running races. The less desirable effect was to induce a dogmatic zeal among sports medicine practitioners who began to extol the dangers of dehydration during exercise. The (il)logic spurring this zeal seems to have been the conclusion that progressive dehydration during exercise will cause heatstroke, which is the most important cause of collapse during exercise. Hence, (i) heatstroke during running can only be avoided if dehydration is prevented, and (ii) all persons who collapse in association with exercise will have a heat disorder, which must be treated with intravenous fluid therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882112 TI - Fluid and electrolyte status in athletes receiving medical care at an ultradistance triathlon. AB - Thirty competitors in the Hawaii Ironman Triathlon were prospectively studied to determine whether fluid and electrolyte disturbances were causes for seeking race day medical care. Athlete weights were significantly (p < 0.0001) decreased during the race, but decreases were not different in treated (n = 11; % delta wt 2.3 +/- 2.9) versus not treated (n = 19; % delta wt - 2.0 +/- 1.9) athletes. Hyponatremia occurred in nine athletes (30%), and hypomagnesemia in six (20%), but only half of athletes were either electrolyte imbalance sought care. Although athletes receiving medical care may have fluid and electrolyte problems, these abnormalities may also occur in healthy athletes. PMID- 7882114 TI - Extravascular axillary vein compression in a competitive swimmer: a case report. AB - An unusual case of acute axillary vein compression secondary to hypertrophy and intramuscular edema of the subscapularis muscle is described in a competitive swimmer. The signs and symptoms of this condition are similar to those of axillary vein thrombosis, including nonedematous swelling, discoloration, pain, and prominent cutaneous veins of the involved upper limb. Early recognition and diagnosis by means of venography are important to distinguish the condition from axillary vein thrombosis and to alert the practitioner to the potential of future axillary vein thrombosis in such a case. The treatment is primarily conservative. PMID- 7882115 TI - Suprascapular neuropathy in athletes: case reports. AB - Shoulder pain and dysfunction is a common problem among athletes, and a great deal of attention is being given to scapular stability and rotator cuff pathology. Two athletes who were first seen with posterolateral shoulder pain and weakness were found to have isolated entrapment of the suprascapular nerve, causing their impairment. Both athletes responded well to conservative treatment, but this entity occasionally requires operative decompression. This article reviews the most common presentation, etiologies, and treatments of suprascapular neuropathy and how it can affect athletic performance. PMID- 7882116 TI - Doping and prevention of doping: international cooperation. PMID- 7882117 TI - Using an objective structured clinical examination to evaluate competency in sport medicine. AB - This article discusses the development, format, administration and scoring of the objective structured clinical examination (OSCE) to evaluate competency in sport medicine. The credentials committee of the Canadian Academy of Sport Medicine has developed an examination to evaluate the competency of practicing physicians in the field of sport medicine. The examination is based on a sport medicine matrix that includes five areas: (a) clinical patient care, (b) team and event coverage, (c) medical/legal issues, (d) teaching and administration, and (e) research. The emphasis is on clinical patient care followed by team and event coverage, with the other three areas having a lesser degree of importance. The OSCE format consists of a number of stations or scenarios based on this matrix. The candidates are evaluated on a check list that reflects the emphasis of each station. A typical clinical patient care problem includes check list items related to the history, physical examination, investigations, diagnosis, and treatment. The candidates are also evaluated for their attitudes and techniques on each station. The examination includes volunteer examiners and patients both simulated and real. The candidates are evaluated through the use of checklists that are filled in by the examiners on optical scoring sheets. These are collated and analyzed to generate comparisons between candidates and to determine the psychometric properties of the overall examination. The examination has consistently scored reliability coefficients of 0.8 or greater. The 1993 examination demonstrated reliability coefficients of 0.89-0.97. Interrater reliability was also calculated, and these values ranged from 0.85 to 0.99. The examination also reflects both face and content validity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882118 TI - Incorporation of screening echocardiography in the preparticipation exam. AB - We sought to evaluate the economic aspects and benefits of adding a limited screening echocardiogram to our annual athletic preparticipation examinations. It was our belief that this screening echocardiogram would add valuable information beyond the history and physical exam alone and could be included in our station by-station format with little increase in time or cost. Controversy exists concerning the best method of detecting cardiovascular conditions that may predispose the athlete to sudden death. During our 1992 preparticipation examinations, we included a single-view parasternal long- and short-axis two dimensional screening echocardiogram. This screening can detect four potentially fatal congenital heart defects. We performed a total of 2,997 echocardiograms at an average cost of $7.34 per examination. Overall 64 echocardiographic abnormalities were found. Mitral valve prolapse and bicuspid aortic valve were the two most common abnormalities. The sensitivity of the history and physical examination in detecting cardiovascular abnormalities was extremely low. Incorporating the echocardiogram into our station-to-station format did not add a significant amount of time to the overall process. We conclude that a screening echocardiogram provides important information and can be used efficiently and economically in the athletic preparticipation examination. PMID- 7882119 TI - Shoulder abduction strength measurement in football players: reliability and validity of two field tests. AB - Musculoskeletal and neurologic injuries affecting shoulder strength are common in contact sports. Full-strength recovery is desired before resumption of competition. On-field assessment of shoulder strength is usually done by manual muscle testing, which lacks sensitivity and reliability. Our objective was to determine the reliability and validity of two field instruments capable of quantifying shoulder abduction strength. Twenty junior football players underwent bilateral isokinetic (60 degrees/s) and isometric shoulder abduction strength measurements using a Cybex 340 isokinetic dynamometer. Test-retest measurements of both shoulders of each player were made using strain gauge (SG) and handheld dynamometer (HHD) instruments. Players were tested during rested and competition conditions. Within and between session reliabilities were calculated using the intraclass coefficient, and validity was assessed using Pearson's correlation coefficient. Overall reliability for each device was calculated using Lisrel analysis. SG was found to be superior to HHD in overall reliability and validity. Within-session reliability in the rested and competition states was 0.75 and 0.78, respectively, for SG and 0.60 and 0.81, respectively, for HHD. Between session reliability in the rested and competition states dropped to 0.51 and 0.63, respectively, for SG and 0.55 and 0.70, respectively, for HHD. Validity was 0.41 and 0.70 for SG when correlated with Cybex at 0 degree and 60 degrees/s respectively. Validity for HHD was 0.28 and 0.42 for Cybex speeds of 0 degree and 60 degrees/s, respectively. SG reliability and validity were similar when testing was done one shoulder at a time or both shoulders concurrently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882120 TI - An analysis and comparison of soccer shin guards. AB - Worldwide > 40 million amateurs participate in the team sport of soccer. With 647,368 injuries occurring from 1989 through 1992, the risk of injury during the play of soccer is evident. Lower extremity injuries have been found to comprise 13.1% of the total injuries in soccer. To date, a comprehensive evaluation of protective equipment utilized to prevent lower extremity injuries in soccer has been lacking. This study utilized a 5th percentile Hybrid III female dummy to evaluate the effectiveness of shin guards in attenuating the forces which can lead to lower extremity injuries. A pendulum impact apparatus simulated one player being kicked by another. Impacts were delivered to the anterior tibial region of the Hybrid III dummy and peak loads were recorded. Load forces were reduced 41.2-77.1% with the utilization of shin guards. Even at extreme temperatures, the guards were found to be effective in lowering the amount of impact force transferred to the shin region. The results of this study indicate that the use of shin guards will attenuate the force of impact to the tibia and thus reduce the risk of injury. PMID- 7882121 TI - The role of the psoas and iliacus muscles for stability and movement of the lumbar spine, pelvis and hip. AB - The activation patterns of the psoas and iliacus muscles were investigated in 7 healthy adult subjects (4 men and 3 women) during a variety of motor tasks in standing, sitting and lying. Myoelectric activity was recorded simultaneously from the 2 muscles using thin wire electrodes inserted under guidance of high resolution ultrasound. In general, both muscles were coactivated, albeit to different relative levels, particularly when hip flexor torque was required. Selective activation of the iliacus could, however, be seen to stabilize the pelvis in contralateral hip extension during standing. Psoas was found to be selectively involved in sitting with a straight back and in contralateral loading situations requiring stabilization of the spine in the frontal plane. During training exercises from a supine position, such as sit-ups, the contribution of the psoas and iliacus muscles could be varied by changing the range of motion as well as the position and support for the legs. Thus, the 2 anatomically different muscles of the iliopsoas complex were shown to have individual and task-specific activation patterns depending on the particular demands for stability and movement at the lumbar spine, pelvis and hip. PMID- 7882122 TI - Long-distance running alters bone anthropometry, elemental composition and mineral density of young dogs. AB - Ten young beagle dogs were run on a treadmill for 1 year, the last 15 weeks 40 km/day. Thereafter bone anthropometric variables, elemental composition, mineral density (BMD) and serum markers of bone metabolism were analyzed and compared with matched-paired control dogs. More osteophytes developed, weight-bearing bones grew larger and BMD of axial skeleton was reduced in the trained group. Zinc and sodium accumulated in bones of the runners. Zinc correlated negatively with BMD. Serum osteocalcin and C-terminal propeptide of type I procollagen did not correlate with the observed differences in BMD. This experiment implies that intensive endurance training in adolescence may reduce the peak bone mass and alter the structural properties of bone. PMID- 7882123 TI - Wrist arthroscopy. AB - Major advancement in arthroscopic equipment and techniques has extended the ability of large joint arthroscopy to be performed in smaller joints. Although wrist arthroscopy is performed in small numbers, the same advantages are afforded as in large joint procedures. It provides important diagnostic information and therapeutic intervention, while avoiding the significant morbidity of open techniques. Patients with mechanical wrist pain are the best candidates for arthroscopy to evaluate ligamentous injuries or triangular fibrocartilage complex injuries. Arthroscopy is also an effective tool in the evaluation and treatment of intra-articular distal radius fractures and is particularly useful in radial styloid fractures. Wrist arthroscopy is a technically demanding procedure. However, it remains a safe and effective method for diagnosis and treatment if performed using a precise technique and if the surgeon has a precise understanding of the anatomy of the wrist. PMID- 7882124 TI - Reliability of functional knee tests in normal athletes. AB - Functional tests are used to determine functional limitations in patients with anterior cruciate ligament injuries. The reproducibility of 4 such functional tests was determined in 21 normal athletes. The athletes performed the four functional tests (figure 8, vertical jump, triple jump test and stairs hopple tests) twice, with an interval of mean 3.9 weeks (1-7 weeks). The reliability of the tests was determined from each tests' coefficient of variation (CV). The figure 8 test showed a significant difference between the 2 performances and the variation from test I to test II. The CV values ranged from 2.0% for the triple jump test to 7.7% for the vertical jump test. These findings do not support the reliability of the figure 8 test and the vertical jump test, but do support the reliability of the triple jump test and the stairs hopple test. PMID- 7882125 TI - Can a regular leg extension bench be used in testing deficits of the quadriceps muscle during rehabilitation? AB - Fifty-nine people, 31 healthy subjects with no previous knee injuries and 28 who had undergone an intra-articular anterior cruciate ligament reconstruction 6-12 months prior to testing took part in the study. The subjects were randomly tested bilaterally on a Cybex 6000 isokinetic testing device (ITD) and on an ordinary leg extension bench (LEB). Strength and endurance were tested with both methods. The linear relationships for paired strength and endurance differences between ITD and LEB were found to be acceptable for the operated group. The LEB alone explained 57% and 38% of the ITD outcome for strength and endurance, respectively. The agreement between observed and predicted ITD values based on the LEB measurements was found satisfactory with a positive standardized agreement index. This indicates that the LEB can be used as a helpful tool in evaluation of quadriceps muscle strength deficits. PMID- 7882126 TI - Adherence to pelvic floor muscle exercise and long-term effect on stress urinary incontinence. A five-year follow-up study. AB - The purpose of this investigation was to study adherence to exercise, pelvic floor muscle (PFM) function and strength and patient satisfaction 5 years after cessation of organized PFM exercise for stress urinary incontinence. All 23 women who had taken part in an "intensive exercise group" in a randomized trial 5 years ago participated in the follow-up study. Structured interview, vaginal palpation and vaginal squeeze pressure were used to assess the condition, PFM function and muscle strength, respectively. Seventy percent of the women were exercising the PFM once a week or more often. Two women were not able to correctly contract the PFM. Mean PFM strength was 18.1 cm H2O. Three had undergone surgery since the initial study. Sixty-one percent were satisfied with their condition. PMID- 7882127 TI - Surgical treatment of medial tibial stress syndrome (shin splint) by fasciotomy of the superficial posterior compartment of the leg. AB - From September 1988 to June 1990, 35 athletes were treated for medial tibial stress syndrome (shin splint) by fasciotomy of the superficial posterior compartment of the leg. Thirty-two patients were available for the follow-up, including self-assessment, clinical examination and activity scoring. The mean postoperative observation time was 16 months. Thirteen patients were performing sports at top international or top national level; 19 patients were competing at different lower levels. Twenty-three patients improved, 7 were unchanged and 2 had poor results. PMID- 7882128 TI - Injuries in national karate competitions in Finland. AB - The injuries sustained in 6 national karate competitions in Finland were studied by analyzing data from 450 bouts during the season 1991-1992. The analyzed data included a personal interview with each competitor and detailed information on the bouts and any injuries sustained. The overall probability of injury was 0.28 per bout. These injuries occurred to 16% of the 647 competitors. Occurrence of injury was greatest among adult men, which was pronounced in final bouts. Of all injuries diagnosed by the physicians for the competitions, more than 95% were localized to the head. The majority of these were minor injuries. Experienced competitors were more injury-prone than beginners. On the other hand, none of the background factors studied significantly affected the probability of injuring one's opponent. Most injuries and penalties, as well as full scores, were caused by direct punches to the head. From these findings it was concluded that a protective guard for the head together with modification of competition rules could significantly reduce injuries. PMID- 7882129 TI - Sagittal plane translation of the tibia in anterior cruciate ligament-deficient knees during commonly used rehabilitation exercises. AB - It may be assumed that exercises that provoke high sagittal plane knee translations also induce high stresses on an anterior cruciate ligament substitute and, therefore, these exercises should be limited during the first months after reconstruction. In 18 patients with unilateral anterior cruciate ligament deficiency, sagittal plane knee translations were measured with a goniometer linkage system during common activities. The largest translations were found during low-speed isokinetic exercises. Further, isokinetic and isometric exercises on the Cybex-II dynamometer provoked in more than 40% of the patients larger translations on the injured than on the healthy knee. However, isometric exercises without distally applied load only provoked small translation. During bicycling, translations increased with increasing resistance similarly in both limbs. Except for walking downstairs, load-bearing exercises, such as sitting down and standing up from a chair and walking upstairs, only produced negligible amounts of tibial translation. In conclusion, during the early phase after anterior cruciate ligament reconstruction, activities such as bicycling and some weight-bearing exercises seem to be more recommendable than low-speed isokinetic exercises, isometric contractions at a low knee flexion angle with distally applied load or walking downstairs. PMID- 7882130 TI - Fracture of the humerus in ball throwers. A consequence of idiopathic juvenile osteoporosis in a female handball player? AB - We report a case of a spontaneous humeral shaft fracture sustained during pitching by a 22-year-old previously healthy female European team handball player. The fracture was treated by closed reposition followed by immobilization in a hanging cast. The fracture healed uneventfully, and normal function and range of motion were reached within 6 months. Between 1 and 2 years after the fracture, bone mineral measurements showed a decreased bone mass (1.43-2.56 SD below mean values of normal women) at all measuring sites; proximal tibia bilaterally (bone mineral content (right) = 2.68 g/cm, bone mineral content (left) = 2.79 g/cm), lumbar spine (bone mineral density (L2-4) = 0.814 g/cm2), and right hip (bone mineral density (neck) = 0.697 g/cm2, bone mineral density (Ward's) = 0.626 g/cm2). A thorough endocrinological examination indicated that a state of bone loss existed, but no specific endocrine disease was found. The unusual fracture presented must be considered the result of the torsional forces transmitted to a severely osteoporotic bone. PMID- 7882131 TI - Arthroscopy of the hip. AB - Arthroscopy has become an important tool in the hands of orthopedic surgeons during the last decades. The hip joint is difficult to approach because it is located deep within the soft tissues covering it, thus decreasing the maneuverability of the instruments. With modern techniques, however, most of the joint space can be visualized. Today, there are several indications for hip arthroscopy and arthroscopic surgery to this joint. The surgical approach is usually made through 3 portals, one directly anterior, and two 2 cm proximal to the tip of the greater trochanter, one anteriorly and the other posteriorly. With a traction force of between 200 and 400 N applied to the leg, the joint space can be widened 5 to 10 mm, allowing space for visualization and surgical instruments. With good surgical technique, the complications are few, and the procedure produces little postoperative morbidity. PMID- 7882132 TI - [Transformation of NIH/3T3 cells and SW 480 cells displaying K-ras mutation]. AB - The spontaneous release of a glyconucleoprotein complex in the supernatant of eukaryote cell cultures is a general phenomenon independent of cell lysis. The DNA recovered from this glyconucleoprotein material contains most part of the genome. The SW 480 cell line, originating from a human colon carcinoma, presents a point mutation of the K-ras gene on both alleles. These cells in culture release the mutated K-ras gene. When crude SW 480 cell supernatant is given, without any other adjonction, to NIH/3T3 mouse cells, transformed foci appear as numerous as those occurring after a transfection provoked by a cloned E.J. ras gene administered as a calcium precipitate. The presence of a mutated ras gene in the transfected foci of the 3T3 cells has been checked by hybridization, after PCR, with an oligonucleotide probe specific to the mutation. This result was confirmed by sequencing the PCR product. PMID- 7882133 TI - [NMDA receptor and long-term potentiation]. AB - In order to evaluate the role of the NMDA receptor redox site in long-term potentiation (LTP), we have investigated the effects of two redox reagents, 5,5' dithiobis-2-nitrobenzoic acid (DTNB) and tris(carboxyethyl)phosphine (TCEP) on the induction and expression of various forms of LTP. DTNB a thiol-oxidizing agent, irreversibly reduces by 50% NMDA receptor EPSP. In the presence of DTNB, the induction of tetanic and anoxic LTP are prevented. When tetanic or anoxic LTP were generated first, DTNB completely reverses the potentiation and TCEP a disulfide-reducing agent restores LTP to its initial level. These redox agents have no effect on AMPA synaptic transmission and did not significantly modify the induction and the expression of tetanic AMPA-LTP. These results suggest that thiol-oxidizing compounds might be useful for the treatment of cerebral ischemia. PMID- 7882134 TI - Alterations of the putative tumor suppressor gene p16/MTS1 in human hematological malignancies. AB - The chromosome band 9p21-22 is frequently rearranged or deleted in a variety of tumors including hematological malignancies. This supports the notion of a tumor suppressor gene in this chromosome region. Indeed, the p16/MTS1 gene encoding a cyclin-dependent kinase (CDK) inhibitor has been shown to be frequently deleted and/or inactivated by nonsense mutations in a number of tumors. We have examined 98 DNA samples from blood, bone marrow cells and lymph node biopsies of patients with leukemia (ALL and AML) or lymphoma (follicular lymphoma and T-cell lymphoma), using Southern blot hybridization and a p16/MTS1-specific probe. Molecular abnormalities, mainly homozygous deletions, were found principally in ALL (8 out of 22 patients), much less frequently in AML (2/32) and lymphoma (2/32). While these data argue in favor of a large involvement of p16/MTS1 in ALL, AML and lymphomas appear to be less frequently implicated. PMID- 7882135 TI - Inducible expression of a neo gene integrated into the human alpha-globin gene cluster. AB - We replaced the 3' flanking region of the human alpha 1-globin gene that binds in vitro the specific transcription factors GATA-1 and AP1/NF-E2, by a neo marker gene using homologous recombination in a MEL (mouse erythroleukemia line) hybrid cell line harbouring a single human chromosome 16. Using an improved method of the neo-positive and HSV-tk negative selection, one correctly targeted clone was obtained out of 164 clones analyzed. In contrast to non-targeted clones, the expression of teh neo gene in the targeted clone acquired the erythroid differentiation-dependent inducibility normally characteristic of the alpha globin genes. No difference was observed in the expression of the human zeta, alpha 2, alpha 1, or theta-globin genes before and after induction of differentiation between the targeted clone and parental cells. These results indicate that, at least in the experimental system used, the 3' flanking region of the human alpha 1-globin gene can be replaced by an exogenous non-erythroid gene without affecting the regulation of the globin genes contained in the alpha globin cluster. PMID- 7882136 TI - High risk genotypes for celiac disease. AB - It is known that celiac disease is strongly associated with an HLA class II component and that most patients carry the dimer DQA1*0501, DQB1*0201. We show in this study that the risk for a carrier of this heterodimer is independent from the number of possible heterodimers, from whether DQA1*0501 and DQB1*0201 are in cis or trans position and from the number of DQA1*0501 (one or two) but strongly depends on the number of DQB1*0201. In the Tunisian population we studied, the risk of developing celiac disease is estimated to be 6.8 times greater for those having a double dose of DQB1*0201 than for other dimer carriers. We replicated this result in published data of four other populations (Italy, Czekoslovakia, United Kingdom, Norway). PMID- 7882137 TI - The yeast I-Sce I meganuclease induces site-directed chromosomal recombination in mammalian cells. AB - Double-strand breaks in genomic DNA stimulate recombination. Until now it was not possible to induce in vivo site-directed double-strand breaks in a mammalian chromosomal target. In this article we describe the use of I-Sce I meganuclease, a very rare cutter yeast endonuclease, to induce site-directed double-strand breaks mediated recombination. The results demonstrate the potential of the I-Sce I system for chromosome manipulation in mammalian cells. PMID- 7882138 TI - [Role of interleukin-4 in the regulation of nitric oxide production by normal human monocytes]. AB - Resting normal human monocytes were found to produce small amounts of cGMP in response to IL-4. This production was inhibited in the presence of LNMMA suggesting an association with activation of the NO synthase (NOS) pathway. In addition, this cGMP generation was abrogated in the presence of either a Ca2+ chelator, EGTA, or a calcium/calmodulin inhibitor, W7, suggesting that IL-4 stimulates the constitutive NOS (cNOS). An enhanced response was observed when monocytes were preincubated with IFN-gamma and whether the cGMP accumulation was still abrogated in the presence of LNMMA it was not affected by either EGTA or W7 suggesting, in that case, the activation of an inducible NOS (iNOS). Taken together these data suggest that IL-4 could stimulate a cNOS in resting and an iNOS in the IFN-gamma-treated human monocytes, indicating that the generation of NO is highly dependent on the maturation state of these cells. PMID- 7882139 TI - [Genetically controlled pharmacomodulation: application to the treatment of HIV infection]. AB - AZT is an inhibitor of HIV reverse transcriptase which active form is AZT triphosphate. Its clinical efficacy is limited by its toxicity and the emergence of mutant resistant viruses. This might be due to an unfficient cellular metabolism of AZT which leads to the intracellular accumulation of AZT monophosphate. We tested a possible enhancement of this metabolism with the HSV1 thymidine kinase, an enzyme that also possesses a good thymidilate kinase activity. We show that, compared to parental cells, the proportion of AZT triphosphate is increased 3 fold in HSV1-TK expressing cells, and that inhibition of HIV replication in these cells requires 3 to 10 fold less AZT. This observation forms the basis for a new gene therapy strategy named genetically controlled pharmacomodulation. PMID- 7882140 TI - Radiosensitivity in vitro of clonogenic and non-clonogenic glioblastoma cells obtained from a human brain tumour. AB - Cells obtained from a human glioblastoma (G5) were characterized and used to develop an assay measuring their radiosensitivity in vitro. Surviving fractions were estimated 12 days after irradiation by image analysis of the total surface occupied by the cells. This report evaluates 4 experimental factors which may influence the radiosensitivity in vitro of G5 cells: passage number, delay between plating and irradiation, cell density and clonal heterogeneity. The radiosensitivity of the G5 cell line was found to be passage-independent at least between passages 12 and 75. Experimental conditions influence the radiosensitivity as surviving fraction at 2 Gy (SF2) range from 90% (5,000 cells/well, irradiation 72 h after seeding) to 49% (2,500 cells per well, irradiation 24 h after seeding). The heterogeneity of the radiosensitivity is large at the clonal level as SF2 of six clones isolated from the G5 line were 45%, 50%, 72%, 74%, 79% and 84%. Finally, when G5 cells were irradiated at low cell density and at the beginning of the growth phase, the radiosensitivity measured with this assay is comparable to that obtained with a standard colony assay. We propose that this assay may be useful to determine the intrinsic radiosensitivity of cells obtained from human tumours. PMID- 7882141 TI - [Enzymatic kinetics and mid-infrared spectroscopy combined with multidimensional data analysis]. AB - An alternate method for enzyme study is proposed. This technique allows enzymatic reactions by a one step assay, and visualisation of variations in FTIR spectral data of substrate during the reaction. Hydrolysis of sucrose by beta-fructosidase is carried out as an example. PMID- 7882142 TI - In vitro selection of antisense oligonucleotides targeted to a hairpin structure. AB - Antisense oligonucleotides are widely used to selectively prevent pre-RNA splicing, mRNA translation or cDNA synthesis from a retroviral RNA template. However, intramolecular folding of the RNA chain can sequester the target sequence into a stable structure. Consequently, the antisense effect can be greatly reduced or even abolished. Hydrogen donor and acceptor sites are still available on nucleic acid bases involved in secondary structures. However, the rational design of antisense sequences able to recognize the three dimensional array of these sites is not available. We used an in vitro selection procedure to fish out aptastrucs, i.e., oligomers able ("apte") to bind to a structure. A population of randomly synthesized oligonucleotides was mixed with the structure of interest and oligodeoxynucleotide sequences bound to the target were selected and amplified. The selection involves the destruction of the unbound candidates by a restriction enzyme. This procedure can be used both for RNA and DNA target structures and does not require the purification of the bound oligonucleotides at each cycle of selection. Several cycles of selection-amplification, followed by cloning and sequencing, allowed us to identify three oligonucleotides able to form a complex with a DNA hairpin. Due to the sequence of the selected candidates, these aptastruc-hairpin complexes involve very likely non-canonical interactions between the two partners. PMID- 7882143 TI - [Changes in the radiation-induced apoptotic response in homozygotes and heterozygotes for the ataxia-telangiectasia gene]. AB - Ataxia-telangiectasia is a progressive recessive disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation hypersensitivity and increased predisposition to cancer. Impaired induction of the tumor suppressor protein p53 after gamma-irradiation was recently reported. All together these characteristics may be compatible with an inability to correctly regulate the apoptotic pathway of cell death in this syndrome. We show here that lymphocyte cultures from AT patients are characterized by a 3 times more elevated spontaneous level of apoptotic cells compared to normal ones. In spite of this, 24 h after exposure to gamma-irradiation (5 to 10 Gy), AT lymphocytes show a dramatically reduced capacity to undergo apoptosis compared to normal cells. We obtained similar results on EBV-transformed lymphoblasts. Interestingly, lymphoblasts from obligate heterozygous for the AT mutation(s) show the same features as AT lymphoblasts, i.e. an elevated frequency of spontaneous and a reduced level of radio-induced apoptotic figures in comparison to normal cultured cells. In conclusion, we show here, for the first time, that mutation(s) in AT gene(s) results in an impaired ability to correctly regulate the apoptotic pathway of cell death. PMID- 7882144 TI - High affinity neurotrophin receptors in cholinergic neurons in the human brain. AB - Tyrosine protein kinases TrkA and TrkC are signal-transducing receptors for nerve growth factor (NGF) and neurotrophin-3 (NT-3), respectively. In the human brain postmortem, using sequential immunohistochemistry, we detected the presence of TrkA and TrkC on 99% and 95% of cholinergic neurons from the basal forebrain and on some cholinergic neurons (22% and 16%, respectively) from the striatum, but not on those from the mesencephalon. These results suggest that some cholinergic neurons, particularly those of the nucleus basalis of Meynert, may be sensitive to both NGF and NT-3 in the human brain. The sensitivity of cholinergic neurons to these two neurotrophins may have a special interest in therapeutic strategies for Alzheimer's disease. PMID- 7882145 TI - Putative dimeric organization of nuclear receptor hormone-binding domains, deduced from hydrophobic cluster analysis. AB - 2D hydrophobic cluster analysis (HCA) protein sequence processing, efficient at low levels of sequence identity, leads to a coherent scheme for the structural organization of the hormone-binding domains (HBDs) of nuclear receptors. The typical serine protease inhibitor (serpin) fold, previously proposed, is confirmed as a likely framework for the hormone-binding domain and leads to a logical dimerization. Furthermore, homo- or hetero-dimerization creates sites where hormone could likely be bound, itself being an active component of the dimerization. This model fulfils many of the biochemical and biological data. PMID- 7882146 TI - YBR1012 an essential gene from S. cerevisiae: construction of an RNA antisense conditional allele and isolation of a multicopy suppressor. AB - The gene YBR1012 was identified during the systematic sequencing of chromosome II of the yeast Saccharomyces cerevisiae. We have inactivated the gene and shown that it is essential for cellular viability. Using antisense RNA technology we have constructed a conditional allele, expression of the antisense RNA strongly inhibits growth. To our knowledge this is the first successful use of antisense RNA technology in S. cerevisiae. Comparison of the deduced ybr1012p sequence with the data banks revealed the presence of a putative phosphatidylinositol kinase domain and a strong homology to the Schizosaccharomyces pombe rad3p. These results suggest that ybr1012p may be involved in signal transduction, possibly related to the control of replication and/or DNA damage repair. The link with DNA damage repair was reinforced by the isolation of the DUN1 gene as a multicopy suppressor of the YBR1012 deletion. PMID- 7882147 TI - [Level of anxiety and effects of moderate noise on early auditory evoked potentials]. AB - Thirty men and 30 women, 20-25 years old, and selected for presence or absence of anxiety were exposed successively for 15 min to four different noises at the same continuous equivalent level LAeq = 75 dB. Auditory brainstem evoked potentials were recorded before and after exposure to each noise. No difference was found between these noises as to their effects upon evoked potentials. After exposure to noise a significant lengthening of L1, L3 and L5 latencies was observed in men; in women a significant lengthening of L3 and L5 latencies was also present. At the same time, I-V and III-V intervals were significantly increased, without any sex-linked difference, and without any change in I-III interval. L3 and L5 latencies are significantly longer in men than in women; lengthening by noise of L1 and L3 latencies was found significantly longer in men than in women; lengthening by noise of I-V interval was found significantly more important in anxious subjects, without any sex-linked difference. L3 lengthening was also found significantly longer in anxious men than in anxiety-free ones. PMID- 7882148 TI - Graft rejection across transgene-encoded MHC class II molecules. AB - To investigate the capacity of class II gene products of the major histocompatibility complex to serve as targets for allograft rejection, we have used lines of transgenic mice which express such genes on a common genetic background. These lines allow us to test the function of single class II molecules, or of single chains of the class II heterodimers, in graft rejection or tolerance induction. Our data show that some class II molecules (A alpha, A beta) can induce very efficient rejection, while others are relatively inert (E), and that tolerance induction requires matching for both chains of the target class II heterodimers. PMID- 7882149 TI - [Fixation and immunological reactivity of parasitic protozoa in sol-gel matrices]. AB - Parasitic protozoa have been entrapped within sol-gel silica matrices. Stationary phase promastigote cells of Leishmania donovani infantum are mixed with a silicon alkoxide solution. They remain trapped within the growing oxide network formed upon hydrolysis and condensation of the alkoxide. Electron microscopy shows the preservation of the cellular organization and the integrity of the plasma membrane of entrapped parasites. Specific antigen-antibody reactions have been performed within the sol-gel matrix via enzyme-linked immunosorbent assays (ELISA) currently used for the diagnostic of visceral leishmaniasis. A clear-cut difference in optical density was measured between positive and negative sera from dogs. Entrapped protozoa antigens are still able to react with specific antibodies through the open porosity of the silica network. These results suggest that sol-gel matrices could be used for the development of immunodiagnostic assays requiring whole cell parasites as antigens. PMID- 7882150 TI - [Detection of human papillomavirus DNA by in situ hybridization and gene amplification]. AB - In situ hybridization with non radioactive probes is attractive for human papillomaviruses (HPV) detection. Its sensitivity has been greatly improved by using different hybridization conditions, techniques for revealing the DNA-DNA hybrids and method of observation and various cell lines derived from human uterine carcinomas (CaSki, SiHa and HeLa cells) which contain 500-600 copies of HPV DNA, 1-2 copies of HPV 16 and 20-50 copies of HPV DNA 18, respectively. In situ gene amplification increased the detection of HPV DNA since hybridization spots were visible in SiHa cells on slides; a specific signal was observed in HeLa cells in suspensions examined by flow cytometry. Confocal microscopy is an alternative method to in situ gene amplification since viral DNA is detectable in SiHa cells with or without gene amplification. Thus, the techniques used in this study are potentially useful for research of single cellular genes. PMID- 7882151 TI - SCID-Hu mouse as a model for human lung HIV-1 infection. AB - HIV induces a multi-organ infection with a dual tropism for both lymphocytes and monocytes/macrophages. The lung is a target both for HIV infection and HIV related opportunistic infections. The SCID mouse has provided the opportunity to develop a small animal model for HIV infection. However, HIV-1 infection of the human fetal thymus and liver (SCID Liv/Thy) implanted in these mice occurred only after direct intraimplant injection of HIV-1 and the resultant HIV-1 infection was restricted to the human thymus. Here we report that human foetal lung can develop in SCID Liv/Thy mice resulting in the development of normal human alveolar and bronchiolar lung compartments which can be productively infected with cell-free HIV-1 virus, leading to a systemic and bifocal infection. This SCID-Hu model should be useful for studying AIDS physiopathology, human viruses with lung tropism and for helping to define gene therapy protocols in lung human cells in vivo. PMID- 7882152 TI - Antilactoferrin autoantibodies associated with HIV infection. AB - Sera from 85 HIV-infected patients were tested for the presence of antilactoferrin antibodies (anti-LF Abs) by specific ELISA. Fifty-seven sera were found positive, including sera from asymptomatic (18/28, 64.3%, mean O.D.: 0.27 +/- 0.05) and symptomatic patients (39/57, 68.4%, mean O.D.: 0.82 +/- 0.15). In the control group, only one out of 26 normal donors show any reactivity (mean O.D.: 0.06 +/- 0.01). None of the tested patients had clinical evidence of vasculitis, the previous reported antilactoferrin-associated pathology and if, in both groups, a similar frequency of anti-LF Abs was found, the autoantibody level was significantly higher among the symptomatic patients (p < 0.01). However, correlation was found neither with polymorphonuclear cell counts nor with the level of circulating lactoferrin. The characterization and the clinical significance of the autoantibodies are under investigation. PMID- 7882154 TI - [The age of genetics]. PMID- 7882153 TI - [Molecular phylogenies and nucleotide insertion-deletion]. AB - Molecular trees based on the analysis of sequence data can be obtained through parsimony procedures. Such approaches identify evolutionary events (homologies and homoplasies and their location in the tree). Nevertheless, it is not possible generally to analyze directly the information given by the aligned sequences. Noticeably, gaps ("indel") need special coding. Standard procedures for coding gaps offer alternatives which suffer of several weaknesses. In this article a new strategy of coding the sequences is defined in view to express the potential phylogenetic information contained in complex zones with internested insertion/deletion and substitutions, contrary to what is done up to the present. This strategy applies without loss or distortion of information to any case where gaps are present in aligned sequences. According to the hierarchy of internested states of characters (sites), this strategy introduces in the data matrix question marks, "?", which are optimized in fine in the cladogram based on all data. These "?" are not missing data, they are methodological codes, neutral to a priori phylogenetic hypotheses. PMID- 7882155 TI - Redox mechanism for the chaperone activity of heat shock proteins HSPs 60, 70 and 90 as suggested by hydrophobic cluster analysis: hypothesis. AB - We have recently shown that the N-terminal ATPase fragment of hsp70 (1-375, composed of domains I and II) as well as the subsequent domain III (376-520) may share three-dimensional similarities with hsp60. In this study, we propose that domain III, common to the hsp60s and hsp70s is also found in the hsp90s and adopts a beta-alpha-beta Rossmann-folded structure which is encountered in the NAD-binding domain of dehydrogenases. Consequently, with the help of the domain IV (in hsp70s and hsp90s) or of hsp10/GroES (in hsp60s) and possibly that of auxilliary partners, the hsp molecules could act as "unfoldases" or "reset systems" by disrupting secondary structures through redox reactions on the main polypeptidic chain with which they interact. The models built on this hypothesis may open up a new way for understanding the chaperone functions within the folding/unfolding processes. PMID- 7882156 TI - Distribution of high density lipoprotein binding proteins among various tissues in the rat. AB - Levels of high density lipoprotein (HDL) in the blood are negatively correlated with heart disease and factors which regulate the levels and metabolism of this important lipoprotein are being investigated by many laboratories. Following the identification in liver of two candidate HDL receptors, HB1 and HB2, we undertook in the present studies, an examination of various other rat tissues for the identification of similar proteins. Using specific antibodies against each of the binding proteins, we identified both HB1 and HB2 in several other tissues (intestine, lung, kidney, ovary ...) and further, revealed relative differences in the expression of HB1 and HB2 between various tissues. A most interesting observation was the presence of HB1 but not HB2 in the spleen. Since the two proteins are not represented equally in all tissues, it is conceivable that these putative receptors have different functions in HDL metabolism or in other biological processes yet to be determined. PMID- 7882157 TI - [Expression of vimentin and GFAP and development of the retina in the trout]. AB - The glial cell development was studied during the edification of the retina and the optic tract, in a teleost, the rainbow trout. The intermediate filament proteins, vimentin and glial fibrillary acidic protein (GFAP) were visualized by an indirect immunohistochemical method. Results show that both vimentin and GFAP are early expressed in the developing retina and, particularly in the Muller cells, a coexpression of vimentin and GFAP is observed from embryonic to adult stages. The ganglion cell layer and the optic fiber layer both exhibit GFAP positive structures. The deep staining for GFAP is also seen in the optic nerve and induces us to credit astrocyte-like cells with a leading role in the pattern formation of this tract. PMID- 7882158 TI - [Normal cerebral aging: study of glial reaction]. AB - Glial fibrillary acidic protein (GFAP), a biochemical marker of astrocytes and glial reaction, was quantified in different brain areas from 16 non-demented patients with a mini mental state score > 25/30 and aged from 21 to 95 years. For each brain, we analyzed the hippocampus (H), the parahippocampus gyrus (GPH) and the neocortical Brodmann areas 9, 22, 39, 44. The quantification of GFAP was performed on the different brain homogenates treated with SDS, using a Western blot method and an immunodetection with a monoclonal antibody against human GFAP. The quantity of GFAP found in the hippocampus and the parahippocampal region were significantly increased as a function of age (p < 0.001). This was not observed for neocortical areas. It has been shown that hippocampal and parahippocampal regions are specifically affected by the Alzheimer-type degenerating process during aging. Glial reaction, as visualized by immunoblotting, could be directly linked to this phenomenon. PMID- 7882160 TI - [Characterization of cDNA of T-cell receptor beta chain in rainbow trout]. AB - Using a two-step PCR strategy, we have cloned several cDNA segments encoding the T-cell receptor beta chain in a Teleost fish, the rainbow trout (Oncorhynchus mykiss). The nine clones analyzed encode identical N-terminal-truncated V beta regions which present limited sequence similarities with several mammalian TcR V beta chains, from residue Tyr-35 to residue Ser-95. These V beta regions are followed by V beta-D beta-J beta-like regions which are different in all the sequenced clones, and by identical C beta regions. The trout C beta domain (156 amino acids) is most related to the chicken and to amphibian (axolotl) C beta domains but no cysteine residue appears in the hinge region. Like in other vertebrate C beta s, the TM region carries a positively charged lysine residue (Lys-271). The intracytoplasmic domain is virtually absent. The possibility to analyze the structure, expression and diversity of a T-cell receptor chain in a Teleost fish model will be important for our future understanding of the evolution of specific immune recognition in vertebrates. PMID- 7882159 TI - Length polymorphism of a microsatellite in human and non human primates. AB - Microsatellites are tandem repeats of short sequences elements (most often CA repeats) interspersed in many genomes and which frequently show multiallele polymorphism. They have proved invaluable for genomic mapping in man and other species and may be used for evolutionary studies provided that the available primers can be used in different species. The dystrophin gene, which shows high sequence conservation between man, rodents and chicken contains such polymorphic CA repeats. Using the oligonucleotides primers developed for testing the polymorphic CA repeat of the 3'untranslated region of the dystrophin gene in man, we achieved the amplification by polymerase chain reaction (PCR) of the analogous region in five non human primates species (Pan troglodytes, Gorilla gorilla, Macaca tonkeana, Macaca fascicularis, Lemur fulvus). All were proved to possess the CA repeat while intraspecies variations of the microsatellite length was observed in chimpanzees, gorillas and tonkean macaques. As it was demonstrated by sequencing, these length variations depend on the number of CA repeats in the microsatellite. PMID- 7882161 TI - [Sequencing of DNA by mechanical opening of the double helix: a theoretical evaluation]. AB - We propose and evaluate a model experiment, in which the sequence of a DNA fragment is determined by mechanically opening the double helix in a controlled manner (e.g. pulling on the 3' end of one strand), and measuring the variation of the force exerted by the base pairs on a nanodynamometer (e.g. on a bead in an optical trap or a glass microneedle attached to the 5' end of the other strand). We show that the major limitation of the approach is the longitudinal elasticity of the already sequenced single strand sections, which soften the displacement force function, and facilitate spontaneous thermal opening of the base pairs. PMID- 7882162 TI - [Role of the elastin-laminin receptor in the vasoregulation]. AB - The elastin-laminin receptor was shown to be present on several benign and malignant cell types and to mediate several important cell reactions such as chemotactic movements of fibroblasts and monocytes, release of lytic enzymes and oxygen free radicals from leucocytes, increased adhesion of mesenchymal cells to elastin fibers as well as modifications of ion fluxes-increase of calcium and sodium influxes and decrease of ouabain-dependent potassium influx. We now demonstrated that the addition of elastin peptides to rat aorta rings precontracted with noradrenaline produced an endothelium-dependent vasorelaxation. The inhibition of this effect by laminin and lactose is in favor of the mediation of this action of elastin peptides by the 67 kDa subunit of the elastin-laminin receptor which possesses a lectin site. As elastin peptides are present in the circulating blood and their concentration was shown to increase in some pathological conditions, this phenomenon may well have physiopathological significance. PMID- 7882163 TI - [Polyclonal DNase abzyme produced by anti-idiotypic internal image method]. AB - The concept of antigen internal image was applied to the production of catalytic antibodies. An antibody raised in rabbits to DNase (Ab1), acted as a competitive inhibitor of the catalysis, and thus was assumed to contain anti-active site Ab. This Ab1 was used to elicit a polyclonal anti-idiotypic antibody (Ab2). This later exhibited a DNA recognition specificity, suggesting the existence of structural internal images mimicking the conformation of the active site. Moreover, Ab2 were able to hydrolyse DNA, indicating the existence of internal images mimicking the enzymatic activity of DNase. Consequently, a strategy can thus be considered using the idiotypic way, for the production of abzymes in the form of internal images of enzyme active sites. PMID- 7882164 TI - Sarcoplasmic reticulum function abnormalities in rabbit failing hearts. AB - In a model of heart failure induced in rabbits by a double volume plus pressure overload, sarcoplasmic reticulum (SR) function was measured by Ca uptake and ryanodine receptor analysis. When expressed per mg of proteins, Ca uptake was decreased by 20% in failing hearts (FH) and ryanodine receptor density was similar in control hearts (CH) and in FH. However Ca uptake and ryanodine receptor density were significantly increased when expressed per total left ventricle suggesting SR hypertrophy. On electron microscopic examination, SR morphology not directly examined but large hypertrophied T tubules were observed suggesting a change in the relationship between membranes and contractile apparatus which may lead to alterations in excitation-contraction-relaxation coupling in spite of minimal biochemical alterations of SR. PMID- 7882165 TI - Localized brain proton MRS metabolic patterns in HIV-related encephalopathies. AB - We have examined 9 healthy volunteers and 63 HIV-patients (16 asymptomatic patients and 47 patients with clinical AIDS-dementia complex, ADC) by magnetic resonance spectroscopy (MRS) and imaging (MRI) on a Siemens Magnetom SP63 (1.5 T). Proton MRS of the brain was performed at 63 MHz using the PRESS sequence (echo time = 135 ms, TR = 1.6 s). Four main results have been found: (1) HIV related encephalopathy induces significant modifications of brain metabolism analyzed by MRS and the most sensitive metabolic parameter is the N-acetyl aspartate/Choline ratio, (2) the correlation between MRS and MRI is good in 75% of patients, (3) in 4 of the 16 neuro-asymptomatic patients (i.e. 25%) a metabolic encephalopathy was found while MRI was still normal, and (4) MR spectra describe 3 different pathological metabolic patterns in the brain of HIV patients. Two patterns might correspond to the two entities of HIV-induced lesions i.e. HIV encephalitis and HIV-related progressive leukoencephalopathy. PMID- 7882166 TI - Lymphocyte-mediated cytotoxicity: two pathways and multiple effector molecules. PMID- 7882167 TI - T cell antigen receptor signaling: three families of tyrosine kinases and a phosphatase. PMID- 7882168 TI - HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization. AB - Nef of primate lentiviruses is required for viremia and progression to AIDS in monkeys. Negative, positive, and no effects of Nef have also been reported on viral replication in cells. To reconcile these observations, we expressed a hybrid CD8-Nef protein in Jurkat cells. Two opposite phenotypes were found, which depended on the intracellular localization of Nef. Expressed in the cytoplasm or on the cell surface, the chimera inhibited or activated early signaling events from the T cell antigen receptor. Activated Jurkat cells died by apoptosis, and only cells with mutated nef genes expressing truncated Nefs survived, which rendered Nef nonfunctional. These mutations paralleled those in other viral strains passaged in vitro. Not only do these positional effects of Nef reconcile diverse phenotypes of Nef and suggest a role for its N-terminal myristylation, but they also explain effects of Nef in HIV infection and progression to AIDS. PMID- 7882169 TI - Discrimination between thymic epithelial cells and peripheral antigen-presenting cells in the induction of immature T cell differentiation. AB - During their intrathymic migration, immature CD4+ CD8+ thymocytes that express a TCR able to recognize the expressed MHC molecules are positively selected, i.e., complete their differentiation program and become mature T cells. Using the immature CD4+CD8+ T cell line DPK, which can be induced to differentiate in culture, we show here that a subset of isolated thymic epithelial cells, but not peripheral antigen-presenting cells, can induce differentiation, suggesting a unique function of these cells in T cell development. In addition, analysis of activation markers induced by thymic epithelial cells versus specific antigen gives the first direct evidence that positive selection is associated with low level cell activation. In contrast with strict affinity-avidity models of thymic selection, we propose that a specialized antigen-presenting cell environment is an essential contributor to TCR-mediated differentiation in the thymus. PMID- 7882170 TI - Murine M290 integrin expression modulated by mast cell activation. AB - Intraepithelial T lymphocytes possess a (TGF beta)-inducible integrin complex that consists of the beta 7 integrin chain in association with a novel alpha chain, murine alpha M290. Using antibodies directed against the murine alpha M290 chain, IL-3-dependent murine bone marrow-derived mast cells demonstrated positive staining after induction with TGF beta. Sequence information from the human intraepithelial T lymphocyte-alpha E gene sequence was used to clone the murine homolog from a TGF beta-induced T cell library. The murine alpha E homolog gene encodes a protein recognized by antibodies to alpha M290. Expression of this gene by bone marrow-derived mast cells was found to be induced by TGF beta or IgE mediated cross-linking of Fc epsilon R1. Furthermore, exposure of murine TK-1 cells to supernatants from activated mast cells induces the expression of the alpha M290 gene, indicating that a mast cell mediator(s) can act in a paracrine manner to induce expression of this integrin complex by other cells. PMID- 7882171 TI - CTLA-4 can function as a negative regulator of T cell activation. AB - CD28 and CTLA-4 are related glycoproteins found on T cells. Ligation of CD28 following antigen receptor engagement provides a costimulatory signal required for T cell activation. Anti-CTLA-4 antibodies were generated to examine the role of the CTLA-4 receptor on murine T cells. Expression of CTLA-4 as a homodimer is up-regulated 2-3 days following T cell activation. Anti-CTLA-4 antibodies and Fab fragments augmented T cell proliferation in an allogeneic MLR. However, when optimal costimulation and Fc cross-linking were present, anti-CTLA-4 Mabs inhibited T cell proliferation. Together, these results suggest that the MAb may obstruct the interaction of CTLA-4 with its natural ligand and block a negative signal, or directly signal T cells to down-regulate immune function. PMID- 7882172 TI - Mice deficient for the CD40 ligand. AB - To study the potential roles of CD40L in immune responses, we generated CD40L deficient mice by gene targeting. Similar to the effects of CD40L mutations in humans (hyper-IgM syndrome), CD40L-deficient mice have a decreased IgM response to thymus-dependent antigens, fail altogether to produce an antigen-specific IgG1 response following immunization, yet respond normally to a T-independent antigen, TNP-Ficoll. Moreover, these mice do not develop germinal centers in response to thymus-dependent antigens, suggesting an inability to develop memory B cell responses. Although CD40L-deficient mice have low levels of most circulating immunoglobulin isotypes, they do not exhibit the spontaneous hyper-IgM syndrome seen in humans, at least up to 12 weeks of age. In summary, our study confirms the important role of CD40-CD40L interactions in thymus-dependent humoral immune responses and germinal center formation. PMID- 7882174 TI - Triacylglycerol turnover in isolated working hearts of acutely diabetic rats. AB - Although myocardial triacylglycerol may be a potentially important source of fatty acids for beta-oxidation in diabetes, few studies have measured triacylglycerol turnover directly in hearts from diabetic animals. In this study, myocardial triacylglycerol turnover was directly measured in isolated working hearts from streptozotocin-induced acutely diabetic rats. Hearts were initially perfused in the presence of 1.2 mM [14C]palmitate and 11 mM glucose for 1 h (pulse) to label the endogenous lipid pools, followed by a 10-min washout perfusion. Hearts were then perfused for another hour (chase) with buffer containing 11 mM glucose +/- 1.2 mM [3H]palmitate. During the chase, both 14CO2 and 3H2O production (measures of endogenous and exogenous fatty acid oxidation, respectively) were determined. A second series of hearts were perfused using the same protocol, except that unlabeled palmitate was used during the pulse and 11 mM [14C(U),5-3H]glucose +/- unlabeled palmitate was present during the chase. Both glycolysis (3H2O production) and glucose oxidation (14CO2 production) rates were measured in this series. Myocardial triacylglycerol levels were significantly higher in the diabetic rat hearts (77.5 +/- 4.6 vs. 33.7 +/- 4.1 mumol fatty acid/g dry mass in control hearts). In diabetic rat hearts chased with 1.2 mM palmitate, triacylglycerol lipolysis was increased, although endogenous [14C]palmitate oxidation rates were similar to control hearts and contributed 10.1% of overall ATP production. The majority of fatty acids derived from triacylglycerol lipolysis were released into the perfusate. In the absence of palmitate, both triacylglycerol lipolysis and endogenous [14C]palmitate oxidation rates were significantly increased in diabetic rat hearts, compared with control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882173 TI - The 1993 Merck Frosst Award. Acetyl-CoA carboxylase: an important regulator of fatty acid oxidation in the heart. AB - It has long been known that most of the energy production in the heart is derived from the oxidation of fatty acids. The other important sources of energy are the oxidation of carbohydrates and, to a lesser extent, ATP production from glycolysis. The contribution of these pathways to overall ATP production can vary dramatically, depending to a large extent on the carbon substrate profile delivered to the heart, as well as the presence or absence of underlying pathology within the myocardium. Despite extensive research devoted to the study of the individual pathways of energy substrate metabolism, relatively few studies have examined the integrated regulation between carbohydrate and fatty acid oxidation in the heart. While the mechanisms by which fatty acids inhibit carbohydrate oxidation (i.e., the Randle cycle) have been characterized, much less is known about how carbohydrates regulate fatty acid oxidation in the heart. It is clear that an increase in intramitochondrial acetyl-CoA derived from carbohydrate oxidation (via the pyruvate dehydrogenase complex) can downregulate beta-oxidation of fatty acids, but it is not clear how fatty acid acyl group entry into the mitochondria is downregulated when carbohydrate oxidation increases. Recent interest in our laboratory has focused on the involvement of acetyl-CoA carboxylase (ACC) in this process. While it has been known for some time that malonyl-CoA does exist in heart tissue, and that it is a potent inhibitor of carnitine palmitoyltransferase 1 (CPT 1), it has only recently been demonstrated that an isoenzyme of ACC exists in the heart that is a potential source of malonyl-CoA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882175 TI - Heterogeneous distribution of a fatty acid analogue uptake in the myocardium of aged rats. AB - The aim of this study was to determine the extent and location of damaged myocardial areas in senescent rats. The viability of myocardial cells was evaluated in virgin young (4 months old) and aged (29 months old) female Wistar rats by analysing the uptake of a slowly metabolisable radiolabelled fatty acid analogue, 15-p-iodophenyl-beta-methylpentadecanoic acid (IMPPA). The biodistribution of IMPPA was measured in various organs, and regional myocardial uptake was specifically assessed using quantitative autoradiography. Myocardial enzymatic activity and DNA content were also evaluated with nitro blue tetrazolium (NBT) and propidium iodide (PI) staining, respectively. In senescent rats, cardiac and renal IMPPA uptake showed a significant (50%) reduction compared with young adult rats and the uptake was not significantly changed in the liver, spleen, lungs, and skeletal muscle. Total ventricular NBT staining and IMPPA uptake were almost homogeneous in young adult rats, whereas they were very heterogeneous in aged rats. In the latter, approximately 11% of the total ventricular volume showed a significantly decreased (by 60% or more) IMPPA uptake compared with normal values, and this reduction was greater in ventricle base than in apex. The myocardial areas unlabelled or poorly labelled by IMPPA represented 4, 5, 6, and 21% of the right ventricular, left ventricular epicardial, septal, and left ventricular endocardial volume, respectively, and were poorly stained with NBT. In some of these areas, PI staining indicated the presence of living cells unable to pick up NBT staining. In conclusion, in young adult rats, no myocardial lesions were observed using three different labelling techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882176 TI - Potentiation by caffeine of the analgesic effect of aspirin in the pain-induced functional impairment model in the rat. AB - The ability of caffeine to potentiate the analgesic effect of aspirin was studied in the pain-induced functional impairment model in the rat. Female Wistar rats received an intra-articular injection of 30% uric acid in the right hind limb, inducing its dysfunction. Once the dysfunction was complete, animals received aspirin oral doses of 0, 0.55, 0.98, and 1.74 mmol/kg with and without 0.17 mmol/kg of caffeine, and the recovery of functionality over time was considered as an expression of analgesia. Blood samples were drawn simultaneously with hind limb functionality determinations, and plasma concentrations of aspirin, salicylic acid, and gentisic acid were measured by high-performance liquid chromatography. Aspirin induced a dose-dependent analgesic effect. Caffeine alone was ineffective. However, caffeine significantly increased the analgesic effect of aspirin at all doses, without modifying aspirin, salicylic acid, or gentisic acid plasma levels. It is concluded that caffeine potentiates the analgesic effect of aspirin by a pharmacodynamic, but not by a pharmacokinetic mechanism. PMID- 7882177 TI - Atrial natriuretic factor, angiotensin II, and the slow component of renal autoregulation. AB - Autoregulation of renal blood flow is highly efficient and is mediated partly by tubuloglomerular feedback (TGF), which couples regulation of blood flow to that of sodium excretion. Atrial natriuretic factor (ANF) dilates preglomerular resistance vessels, in which autoregulation occurs, and has been reported to inhibit TGF. This study addressed potential actions of ANF on the slow, TGF mediated, component of autoregulation. Renal blood flow was measured by an electromagnetic flow probe in Sprague-Dawley rats anesthetized by halothane or isoflurane while renal perfusion pressure was manipulated by a servo-controlled clamp placed on the aorta between the renal arteries. Progressive reduction of perfusion pressure to 60 mmHg (1 mmHg = 133.3 Pa) induced resetting of autoregulation to operate at the reduced pressure and to defend lower renal blood flow. Infusion of ANF at a dose shown to reliably increase sodium excretion did not affect autoregulation or its resetting. Because resetting is angiotensin II dependent, the converting enzyme inhibitor Enalaprilat was used to provide angiotensin II blockade. As expected, autoregulation did not reset to operate at reduced perfusion pressure. Again ANF was without effect. In a third experiment, relaxation of resistance was assessed in response to repeated steps of perfusion pressure between 65 and 75 mmHg. Time constants of constriction and dilatation were recovered by fitting to a single exponential before and during ANF infusion. Time constants ranged form 0.045 to 0.055 Hz, were consistent with operation of TGF, were not different for constriction or dilatation, and were unaltered by ANF; nor did ANF affect the magnitude of constriction or dilatation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882178 TI - Endothelium-dependent relaxations in canine coronary arteries are enhanced in early heart failure and persist in recovery. AB - In vitro coronary artery responsiveness to noradrenaline, phenylephrine, and BHT 920 together with functional relaxation to acetylcholine was assessed in dogs at the early onset of pacing-induced heart failure (1 week) and in dogs recovered from heart failure (3 weeks paced, followed by 4 weeks discontinued pacing). alpha-Adrenoceptor stimulation produced contractile responses that were unaltered in early congestive heart failure and recovery. Contractions to noradrenaline and BHT-920 were always less than those produced by phenylephrine. Endothelium-intact arteries demonstrated relaxations in response to noradrenaline and BHT-920, but not phenylephrine. Relaxations to noradrenaline were enhanced 24% in early heart failure and 47% following recovery from heart failure, compared with control. BHT 920 produced relaxations that were augmented 21 and 76% in early heart failure and recovery, respectively. Contractile sensitivity to noradrenaline increased 5 fold in early heart failure and was not different in recovery, compared with control. Contractile sensitivity to BHT-920 and phenylephrine was unaltered throughout. Acetylcholine produced relaxations that were increased 21% in early heart failure and 13% after recovery from congestive heart failure. Furthermore, acetylcholine sensitivity was significantly enhanced in early heart failure and recovery. The current study reveals a progressive adaptation of the coronary endothelium in congestive heart failure, possibly directed towards protection against excessive vasoconstriction due to circulating catecholamines. PMID- 7882179 TI - A radioimmunoassay for oncorhynchid growth hormone targeted to the physiological range. AB - This study describes the development of an oncorhynchid growth hormone (GH) radioimmunoassay using recombinant chum salmon GH (rsGH) and a rabbit antiserum (TJK-1) raised against this recombinant material. The assay was designed to measure the wide range of circulating immunoreactive GH (IRGH) levels in Pacific salmonids, resulting in a standard curve capable of accurately determining plasma levels of IRGH from 0.5 to 250 ng/mL without dilution. The assay ED50 and ED90 values averaged 13.1 and 0.5 ng/mL, respectively. This radioimmunoassay specifically recognizes oncorhynchid IRGH, showing no cross-reactivity with recombinant porcine and bovine GH, or natural chum salmon prolactin at concentrations up to 10 micrograms/mL. Curves approximately parallel to the standard curve were obtained with purified natural coho salmon GH and plasma from chinook salmon. Recovery of rsGH from plasma was complete over the full range of the standard curve. Intra- and inter-assay coefficients of variation were 6.0 and 12.9%, respectively. Plasma IRGH levels in fed coho salmon were 30.6 +/- 5.3 ng/mL, while those in fish starved for 2 weeks were 132.9 +/- 53.9 ng/mL. Starvation for an additional 4 weeks had no significant effect. Plasma IRGH levels in control rainbow trout injected with saline were significantly higher 45 min post-injection. In contrast, fish injected with recombinant porcine GH exhibited no elevation in IRGH. It is speculated that exogenous GH inhibits the production of endogenous GH. PMID- 7882180 TI - meta-iodobenzylguanidine uptake in the hypertensive-diabetic rat heart: a marker for myocardial dysfunction? AB - The purpose of this study was to investigate the cardiac adrenergic neuronal changes induced by diabetes and hypertension by using an analogue of norepinephrine, meta-iodobenzylguanidine (MIBG), and to compare these changes with the contractile state of ventricular papillary muscle. The tissue concentration of norepinephrine in the cardiac apex was also measured for direct comparison with [123I]MIBG uptake. One week following the induction of diabetes by streptozotocin injection (55 mg/kg, i.v.), male Sprague-Dawley rats were given subcutaneous injections of a hypertension-inducing agent, deoxycorticosterone acetate (DOCA, 25 mg/kg), or DOCA vehicle twice weekly for 3, 6, 9, or 12 weeks. At the end of each time point, the animals were injected intravenously (15 mCi/mg; 1 Ci = 37 GBq) with [123I]MIBG. The results showed a progressive decrease in MIBG uptake into the hearts of diabetic, hypertensive, and diabetic hypertensive rats during the 12-week observation period, compared with the control group. However, length-tension papillary muscle studies at 12 weeks indicated that only the diabetic group had a diminished performance compared with control. Furthermore, an inverse relationship was observed between MIBG uptake and norepinephrine levels in the cardiac apex of the diabetic and diabetic hypertensive groups. Therefore, we concluded that either MIBG does not provide an accurate indication of adrenergic integrity or that there is no relationship between sympathetic activity and myocardial function at the time points measured. MIBG did not prove to be a useful marker for myocardial dysfunction in diabetic rats. PMID- 7882181 TI - Proximal tubular function in transgenic mice overexpressing atrial natriuretic factor. AB - A transgenic mouse model in which atrial natriuretic factor (ANF) expression is targeted to the liver was used to study intrarenal adjustments to the chronically elevated hormone level. Such animals, designated TTR-ANF, are characterized by reduced arterial blood pressure but similar sodium excretion compared with nontransgenic siblings. Proximal tubular micropuncture gave the following results: single-nephron filtration rate = 12.7 +/- 1.1 vs. 15.6 +/- 1.9 nL/min (TTR-ANF versus nontransgenic, ns); end-proximal tubular fluid/plasma concentration ratio of inulin = 1.93 +/- 0.09 vs. 1.97 +/- 0.15 (ns); fractional reabsorption of sodium = 45.5 +/- 2.8 vs. 46.0 +/- 3.8% (ns); fractional reabsorption of chloride = 33.6 +/- 3.3 vs. 32.4 +/- 4.1% (ns). These data indicate that life-long elevation of plasma ANF concentration was not associated with significant alteration in single-nephron filtration rate and proximal tubular function. We conclude that compensatory antinatriuretic mechanisms, localized downstream from the proximal tubule, can prevent ANF natriuresis. PMID- 7882182 TI - The endothelium contributes to the contractile responses of the human umbilical artery to 5-hydroxytryptamine and endothelin-1 under low but not high PO2 conditions. AB - To determine the influences of both PO2 and the presence of the endothelium on contractile responses of the human umbilical artery (HUA), the effects of a series of vasoconstrictors were compared in ring preparations with and without endothelium at low (2.5% O2, PO2 < 55 mmHg (1 mmHg = 133.3 Pa)) and high PO2 (95% O2, PO2 > 600 mmHg). The results demonstrate the following. (i) 5 Hydroxytryptamine (5-HT) and endothelin-1 (ET-1) contracted the HUA at either low or high PO2. At low PO2, removal of the endothelium significantly reduced receptor-mediated responses. (ii) The nitric oxide synthase inhibitor N omega nitro-L-arginine methyl ester (L-NAME, 100 microM) did not modulate 5-HT initiated contractions at either level of PO2. (iii) alpha-Methyl-5 hydroxytryptamine (alpha-Me-5-HT) and 5-carboxamidotryptamine (5-CT), relatively selective 5-HT1C/5-HT2 and 5-HT1-like receptor agonists, respectively, elicited contractions in the HUA, and the responses were reduced at low PO2 but unaffected by removal of the endothelium. (iv) Responses of the HUA to high potassium (hK+) were unaffected by either changes in PO2 or removal of the endothelium. (v) The 5 HT2 receptor antagonist ketanserin at low concentration (10 nM) inhibited contractile responses to 5-HT in an apparently competitive manner. However, with 100 nM ketanserin and at low PO2, inhibition became noncompetitive. Removal of the endothelium did not influence the action of ketanserin. (vi) Regardless of PO2, the Ca2+ channel antagonist nifedipine (1 microM) significantly inhibited 5 HT- and ET-1-mediated contractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882183 TI - Quantitative measurements of dietary and [1-14C]linoleate metabolism in pregnant rats: specific influence of moderate zinc depletion independent of food intake. AB - Our objective was to investigate whether the effects of moderate zinc deficiency on metabolism of linoleate during pregnancy could be distinguished from the effects of low food intake. Rats were force-fed an isoenergetic zinc-deficient (3.2 mg/kg) or control (26.4 mg/kg) semiliquid diet during the second half of pregnancy. Fatty acid quantity and composition in both maternal and fetal organs were analyzed at term. Recovery of 14C in lipid- and water-soluble metabolites from orally injected [1-(14)C]linoleate was also studied. After 10 days of gavaging identical amounts of the diet, zinc-deficient rats had lower serum zinc and lower uterus and placenta weights than controls, but body weights were similar. At term, zinc-deficient rats had a fatty acid composition in organs and carcass similar to that of the controls, but the zinc-deficient fetuses had lower long-chain n-6 and n-3 polyunsaturates in brain, liver, and carcasses. Lipids extracted from most organs of zinc-deficient rats contained lower 14C levels, but 14C was raised in the maternal carcass lipids and in water-soluble metabolites. We conclude that zinc deficiency during pregnancy increases oxidation of linoleate and decreases synthesis or transport of polyunsaturates to the fetuses and that these effects are independent of depressed food intake, i.e., they are specific to zinc depletion. Thus, zinc deficiency has distinct effects on fatty acid metabolism, which are readily observed using 14C tracer methods. PMID- 7882184 TI - Studies on ethanol-induced subepithelial fluid accumulation and jejunal villus bleb formation. An in vitro video microscopic approach. AB - Jejunal intraluminal ethanol causes morphological and mucosal microvascular injury. The purpose of the present study was to understand the mechanism of the morphological alterations caused by ethanol without the influence of ethanol's effect on the microcirculation. Therefore, we have investigated the ethanol induced morphological changes in the absence of blood flow (i.e., in the jejunum in vitro) and compared these changes with those reported to occur in the presence of microcirculation (i.e., in the jejunum in vivo). The mucosa of jejunal segments was exposed to a control solution and to solutions containing 0.8, 1.6, and 4.8% (w/v) ethanol, using a specially designed apparatus. The morphological response of the mucosa to these solutions was continuously examined employing a video microscopic technique, and the changes were morphometrically evaluated on subsequent playback of videotapes. Ethanol caused a concentration-dependent increase in the number of villi with subepithelial fluid accumulation, i.e., blebs, and a decrease in the height of the villus core (i.e., lamina propria). With 0.8 and 1.6% ethanol, the contracted core remained partially attached to the epithelium and the total villus height (villus core plus epithelial layer) decreased. With 4.8% ethanol, the villus core contraction was so rapid that the stroma fully separated from the epithelium. Thus, among other factors, the rapidity of the villus core contractions appears to play a role in the subepithelial bleb formation and in the appearance of the bleb. The ethanol induced changes in vitro are similar to those reported to occur in the jejunum in vivo. Therefore, we conclude that the effect of ethanol on morphology is independent of its action on the microcirculation. PMID- 7882185 TI - Gender differences in cardiovascular responses to the cold hand pressor test and facial cooling. AB - To test the hypothesis that changes in systemic vascular resistance (SVR) contribute to the differences in arterial blood pressure responses between men and women to local cold pressor tests, nine normotensive men (25.9 +/- 5.9 years old) and women (24.4 +/- 5.9 years old) performed the cold hand pressor test (CPT; 6 min in 5 degrees C water) in the supine position. A subgroup of men (n = 5) and women (n = 5) from the CPT were exposed to 6 min of facial cooling (FC) by circulating cold water (5 degrees C) through a perfusion mask. Using standard auscultatory techniques, pre-experimental systolic and diastolic blood pressures were found to be significantly higher (p < or = 0.05) in males than females. During the initial 2 min of CPT and FC, both males and females experienced similar relative increases in pressure. Thereafter, only the males maintained an elevated pressor response, whereas the females progressively declined. The gender related trends in blood pressure can be explained by differences in SVR, with the males exhibiting significantly greater changes in SVR than females during min 4-6 in CPT. Heart rate increased (p < or = 0.05) in both groups, with the greater rise occurring in females at each minute of CPT. Throughout FC, the changes in SVR were similar between groups, with the exception of the 6-min value being greater than baseline in men but not women. No differences in heart rate or cardiac output were observed between groups during FC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882186 TI - Excitatory cardiovascular and respiratory effects of baclofen in intact rats. AB - The rat has become the preferred animal model for study of the central control of the cardiorespiratory system. However, data in the literature suggest that the role of GABAB receptors in control of the respiratory timing may be different in rats from that in other species. Therefore in this study we investigated cardiorespiratory effects of repeated injections of 0.5 nM baclofen and 50 nM CGP35348, GABAB receptor agonist and antagonist, respectively, applied into the fourth ventricle of urethane-anesthetized intact, spontaneously breathing Wistar rats. Baclofen increased arterial blood pressure (ABP), heart rate, inspiratory time (Ti), and the rate of rise (Di/t) and peak amplitude of the integrated diaphragmatic EMG (Di). Expiration (Te) was unaffected. CGP35348 reversed the ABP and Di effects of baclofen and decreased Di/t and Te below their control values, whereas Ti remained prolonged. These excitatory effects of baclofen are consistent with previously reported effects of low i.v. doses of baclofen in cats, and suggest that GABAB receptors may modulate the depth and duration of inspiration. We conclude that the intact rat represents a suitable animal model for investigations of the integrated control of cardiorespiratory functions. To our knowledge this is the first investigation reporting excitatory effects of GABAB receptor stimulation on inspiratory activity in rats. The depressant effects of baclofen on the respiratory rhythm reported in the rat "isolated" brain in situ, and the neonatal rat brainstem--spinal cord in vitro seem to be unique for those specific preparations. PMID- 7882187 TI - Gastric inhibitory polypeptide and glucagon-like peptide-1(7-36) amide exert similar effects on somatostatin secretion but opposite effects on gastrin secretion from the rat stomach. AB - Previous studies on the isolated perfused stomach have shown that gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1(7-36) amide (GLP-1(7-36) amide) stimulate release of somatostatin (somatostatin-like immunoreactivity, SLI). GIP produced a paradoxical increase in gastrin secretion, whereas GLP-1(7 36) was inhibitory. In the current study, the actions of synthetic (sp) and native (np) porcine and synthetic human (sh) GIP, GLP-1(7-36), and GLP-1(7-37) on SLI and gastrin secretion were compared using a gradient perfusion of peptide. All peptides increased SLI secretion at a threshold concentration of approximately 50 pmol/L (p < 0.05). The initial rate of increase in response to spGIP (119 +/- 39 pg/min) was greater than with other forms of GIP or GLP-1. Maximal increases obtained with the two porcine peptides did not differ. Gastrin secretion was increased by concentrations of spGIP and npGIP similar to those increasing SLI secretion, but the maximal response to shGIP was lower. In contrast to GIP-induced increases, both GLP-1(7-36) and GLP-1(7-37) suppressed gastrin secretion. It is concluded that human and porcine GIP, GLP-1(7-36), and GLP-1(7-37) all stimulate SLI secretion but with different maximal effects, and GIP stimulates gastrin secretion whereas both forms of GLP-1 inhibit gastrin secretion. PMID- 7882188 TI - Reduced oxygen consumption of brown adipocytes isolated from progesterone-treated rats. AB - It has been previously shown that responsiveness to noradrenaline is reduced in brown adipocytes isolated from estradiol-treated rats. The possibility that high plasma levels of progesterone could also alter adrenergic response was checked. The oxygen consumption of brown adipocytes isolated from control and progesterone treated rats was monitored in basal conditions and in the presence of increasing concentrations of noradrenaline. In both situations, cells isolated from treated animals showed a lower respiratory rate than those from control animals. These results suggest that not only estradiol but also progesterone could modulate the adrenergic response of brown adipocytes. The study of alpha 1- and beta adrenergic responses indicates that the beta-response parallels the general reduction in oxygen consumption, although the alpha 1-response seems to be more deeply depressed. Estimation of cell number in brown fat depots indicates some hyperplasia induced by progesterone; this increase in cell number could counterbalance partially but not totally the decreased cellular oxygen consumption at the organ level. PMID- 7882189 TI - Preservation of sarcoplasmic reticulum Ca2(+)-sequestering function in homogenates of different type composition following sprint activity. AB - To examine the effect of exercise on sarcoplasmic reticulum function in muscle tissue of different fibre composition, adult male Wistar rats weighing 388 +/- 23 g (x +/- SE) ran intermittently on a treadmill until fatigue. Fatigue was induced by 15-20 min of running performed at 52 m/min on an 8 degrees incline in periods of 2.5 min of exercise separated by 2 min of recovery. Analysis of sarcoplasmic reticulum Ca2+ ATPase activity determined in homogenates indicated no difference (p > 0.05) between age-matched control and exercised tissue for the soleus (SOL; 0.121 +/- 0.012 vs. 0.156 +/- 0.018 mumol.mg-1 protein.min-1), red gastrocnemius (RG; 0.381 +/- 0.022 vs. 0.354 +/- 0.022), or white gastrocnemius (WG; 0.526 +/- 0.05 vs. 0.471 +/- 0.031). Similarly, both total ATPase and Mg2+ ATPase activities were unaffected by the exercise in any of the tissues examined. Exercise also failed to alter sarcoplasmic reticulum Ca2+ uptake in homogenates of the SOL (1.43 +/- 0.15 vs. 1.38 +/- 0.19 nmol.mg-1 protein.min-1), RG (3.74 +/ 0.29 vs. 3.59 +/- 0.24), and WG (5.98 +/- 0.48 vs. 5.41 +/- 0.50). At fatigue, glycogen depletion was similar in all tissue types and amounted to 65.1% in the SOL (172 +/- 9 vs. 60 +/- 16 mmol.glucosyl units-1.kg-1 dry weight), 74.4% in RG (164 +/- 8 vs. 42 +/- 6), and 79% in the WG (167 +/- 9 vs. 35 +/- 9). It is concluded that exercise by itself does not alter sarcoplasmic reticulum Ca2(+) sequestering function in tissues of primarily different fibre composition when determined in homogenates in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882191 TI - The antiadrenergic effect of cyclopentyladenosine on myocardial contractility is reduced in vivo in diabetic rats. AB - The aim of this study was to test the hypothesis that the antiadrenergic action of adenosine is reduced in diabetes. This was determined by evaluating the effect of experimental diabetes mellitus on the in vivo myocardial antiadrenergic action of cyclopentyladenosine, and adenosine A1-receptor agonist. Changes in heart rate and ventricular performance in response to infusion of dobutamine, a beta 1 adrenergic agonist, were determined in the absence and presence of cyclopentyladenosine, in anesthetized, 10- to 12-week male diabetic (60 mg/kg streptozotocin), insulin-treated diabetic and control rats. Intravenous dobutamine (16 micrograms/kg) increased +dP/dtmax and -dP/dtmax in control rats from 7,706 +/- 553 and 5,449 +/- 403 mmHg/s (1 mmHg = 133.3 Pa) to 19,170 +/- 465 and 8,855 +/- 317 mmHg/s, respectively. In diabetic rats dobutamine increased +dP/dtmax and -dP/dtmax from 5,733 +/- 541 and 4,016 +/- 426 to 15,015 +/- 1,521 and 7,039 +/- 809 mmHg/s, respectively. Cyclopentyladenosine significantly attenuated dobutamine-stimulated increases in +dP/dtmax and -dP/dtmax in both control and diabetic rats in a dose-dependent (0.1-3.0 micrograms/kg) manner. Cyclopentyladenosine potency to attenuate dobutamine-enhanced +dP/dtmax was reduced significantly (p < 0.05) in diabetic rats compared with controls (ID50, 1.07 vs. 0.59 micrograms/kg, respectively) with no change in efficacy. The magnitude of cyclopentyladenosine inhibition of dobutamine-enhanced -dP/dtmax was greater in control than diabetic rats (81 vs. 54%, respectively), but ID50 values were not different. Insulin treatment of diabetic rats prevented the observed changes. These data suggest that the antiadrenergic action of adenosine is compromised in diabetes and that this may contribute to the development of diabetic cardiomyopathy. PMID- 7882192 TI - In vivo correlation between liver and blood energy status as evidenced by chronic treatment of carbon tetrachloride and adenosine to rats. AB - Several tissues, such as red blood cells, depend on the liver supply of the purine ring for adenine nucleotide synthesis. We explored whether progressive liver damage, induced by carbon tetrachloride (CCl4), is accompanied by alterations in liver and blood energy status. After 4 weeks of CCl4 treatment, liver ATP, ATP/ADP, and energy status were decreased. Blood ATP remained normal, whereas the blood energy status was also diminished. After 8 weeks the changes were more evident, and a significant decrease of total liver nucleotides was also found. In the blood, the changes paralleled those in the liver. Simultaneous administration of adenosine counteracted the CCl4 effects. A good correlation (r = 0.79, p < 0.01) between the liver and blood ATP changes and a very significant relationship between liver and blood ATP/ADP ratio (r = 0.92, p < 0.001) were observed. Therefore, the data suggest that liver function could influence the energy availability in other tissues, such as red blood cells, perhaps as a result of its capacity to provide purine rings for extrahepatic synthesis of adenine nucleotides. PMID- 7882190 TI - Methimazole protection of rats against gentamicin-induced nephrotoxicity. AB - Methimazole was previously shown to protect rats, mice, and (or) dogs against cisplatin-, cephaloridine-, 2-bromohydro-quinone-, and S-(1,2-dichlorovinyl)-L cysteine-induced nephrotoxicity. In this study, methimazole effects on gentamicin (GM) induced nephrotoxicity were examined. Rats given GM (40 mg/kg) twice daily for 10 days exhibited higher blood urea nitrogen (BUN) concentrations and severe necrosis of virtually all proximal tubules compared with saline-treated controls. Rats cotreated with methimazole (20 mg/kg) exhibited minimal proximal tubular necrosis and were protected against GM-induced increase in BUN concentrations, despite having higher kidney GM concentrations. Rats given GM alone for 3 days exhibited no proximal tubular necrosis and no elevation of BUN values. However, these rats exhibited an increase in nonprotein disulfide concentrations and a decrease in renal protein thiol and protein disulfide concentrations, as opposed to rats given GM and methimazole. Together the results show that methimazole was an effective antagonist of GM-induced nephrotoxicity. Methimazole did not inhibit GM renal uptake but may protect against GM-induced nephrotoxicity by acting as an antioxidant within the kidneys. PMID- 7882193 TI - Determinants of health-promoting lifestyles in adolescent females. AB - The relationship between health-promoting lifestyle and definition of health, perceived health status, self-efficacy, maternal and paternal health-promoting lifestyle, and selected demographics in adolescent females was investigated. Included in the study were 184 adolescents and their parents. A modification of Pender's (1982, 1987) Health Promotion Model provided the conceptual framework for the study. Two research questions evolving from the conceptual model guided the study. Results indicated that mothers' and fathers' health-promoting lifestyles were significantly correlated with their daughters' health-promoting lifestyles. A strong relationship existed between the predictor variables of definition of health (clinical, functional, and eudaemonistic subscales), self efficacy, perceived health status, and ethnicity, and the criterion variable of adolescents' health-promoting lifestyles. Together these variables accounted for 41% of the variance in adolescent health-promoting lifestyle scores. Implications for nursing research and practice are discussed. PMID- 7882194 TI - Mental health consumers as public educators: a qualitative study. AB - This qualitative study documented the subjective meaning to mental health consumers of participation in high school students' education sessions. The purpose was two-fold: to uncover the meaning of human experiences through the analysis of participants' descriptions, and to document the step-by-step process of conducting qualitative nursing research. Data collection included field notes, semi-structured interviews, open-ended questions, and observation of six mental health consumers with major psychiatric illnesses. Interviews were recorded in both handwritten and audio forms. All field notes and interviews were transcribed. Techniques of bracketing, intuiting, analyzing, and describing were employed to identify and cluster natural meaning units, and to synthesize the focal meaning(s) (Banonis, 1989). The key phenomena were: positive experience, increased self-esteem, and introspection. The results indicate that a collaborative relationship between nurses and mental health consumers can be a growth-promoting experience for the consumers. PMID- 7882195 TI - Changes in employment status: the experiences of Ontario registered nurses. AB - Telephone survey data were collected from 1,056 Ontario registered nurses to examine employment status (full-time, part-time, casual employment) of nursing professionals over time, through a detailed analysis of different forms of employment status change or mobility. Both internal (within-job) and external (between-job) forms of employment status change were investigated. The survey data revealed that the average duration of employment careers was 16.7 years (+/- 9.2 years), 78.5% of survey respondents reported at least one change in employment status over the course of their working careers, and 54.9% reported two or more changes over time. Changes in family status (changes in marital status and having children during employment career) were shown to be strongly associated with greater external employment status mobility. The duration of jobs was found to be strongly associated with greater internal employment status mobility. Implications for improved flexibility in employment status within health care settings are discussed. PMID- 7882196 TI - Supporting: men's experiences with the event of their partners' miscarriage. AB - The purpose of this study was to investigate men's experiences with the event of their partner's miscarriage. Grounded theory methodology was employed to gather data from eight men whose partners had experienced a total of 10 miscarriages. Data were collected through informal, unstructured interviews. Four sequential phases emerged from the data: (a) recognizing sign(s), (b)confirming the news, (c) working through it, and (d) getting on with life. Supporting was the basic social process that emerged, and four major concepts arose: (a) living the feelings, (b) waiting, (c) seeking help, and (d) accepting. The implications for practice are examined and recommendations for future research are presented. PMID- 7882197 TI - A reactionist professional association: the Provisional Council of University Schools and Departments of Nursing, 1942-1948. AB - From its inception in 1942, the Canadian Association of University Schools of Nursing (CAUSN) has developed into the accrediting agency for university nursing programs and the national voice for its 30 member schools. The current research examines the creation in 1942 of the Provisional Council of University Schools and Departments of Nursing, the forerunner of the CAUSN. The research is historical in design. Primary and secondary data were collected and analyzed inductively. Primary data consisted of archival documents located in the Queen's University Archives, Kingston, Ontario and the Canadian Nurses Association (CNA) Archives, Ottawa, Ontario. Secondary data augmented and corroborated analysis of primary data and included published histories of the CAUSN and the CNA, as well as books and articles about the development of university nursing education in Canada. The impetus for the inception in 1942 of the Provisional Council of University Schools and Departments of Nursing originated with the CNA. The Provisional Council subsequently achieved none of its stated goals. Instead, it focused on its relationship with the CNA and contested the need for its own existance. The Provisional Council was a reactionist association that reflected the uncoordinated nature of university nursing education and the inability of university nursing educators to set aside parochial differences. PMID- 7882198 TI - History: a way of knowing. PMID- 7882199 TI - Institute for Philosophical Nursing Research. PMID- 7882200 TI - Osler-Weber-Rendu disease. PMID- 7882201 TI - Aseptic encapsulation of retained surgical sponge. PMID- 7882202 TI - Radiology for the surgeon. Radiation-induced sarcoma of bone. PMID- 7882203 TI - Problem-based learning: its role in undergraduate surgical education. AB - OBJECTIVE: To familiarize the surgeon with problem-based learning (PBL) and to discuss the current and future role of PBL in undergraduate surgical education. DATA SOURCES: Two meta-analyses comparing the outcome of a PBL curriculum with a traditional curriculum and other studies in the English-language literature. STUDY SELECTION: Data on the effectiveness of PBL can best be assessed by a meta analysis in which the conclusions of many studies are reviewed and combined to provide a more comprehensive picture. The studies chosen represent those from the only two recent meta-analyses of the problem that have appeared in reputable journals. DATA EXTRACTION: Results reported are those obtained using appropriate techniques and published in reputable journals. Information relevant to the major issues in undergraduate surgical training was selected for inclusion. DATA SYNTHESIS: PBL depends on self-directed learning, triggered by a clinical problem. The students meet in small groups led by a facilitator and discuss carefully designed clinical cases. At the conclusion, the students will have encountered all the information necessary to solve the case and, in so doing, will have gained knowledge that in a conventional curriculum would usually have been disseminated by lecture. There were only small differences between graduates from the two types of curricula. Those from a PBL curriculum had comparable examination results to those from a traditional curriculum on both basic science and clinically based examinations but were happier with their educational experiences. CONCLUSIONS: Centres that have adopted a PBL approach have found improved student motivation and enjoyment, but there has been no convincing evidence of improved learning. An intelligent combination of both traditional and PBL approaches will likely provide the most effective training for undergraduate surgical clerks. PMID- 7882204 TI - Attitudes toward trauma care of surgeons practising in Ontario. AB - OBJECTIVE: To assess the attitudes of practising surgeons in the province of Ontario toward issues in trauma care management. DESIGN: A survey by questionnaire. SETTING: The study was carried out in a university-affiliated hospital. The survey respondents generally practised in a nonteaching setting; 48% were over the age of 50 years; 81% worked in an institution with 24-hour in house physician coverage for the emergency department. SUBJECTS: All 2294 surgeons registered with the Ontario Medical Association were surveyed by completion and return of a questionnaire; 191 surgeons were registered in Ontario but were not practising in the province and were excluded from the survey. Questionnaires were completed by 575 surgeons, but 49 were no longer in active practice, so 526 responses form the basis of this analysis. RESULTS: The response rate to the questionnaire was 27%. One-third of the respondents wished to treat no trauma patients at all; 47% believed that trauma patients had a negative impact on their surgical practice; only 19% considered that trauma patients had a positive impact. Surgeons had negative attitudes toward trauma because of the night and weekend profile of trauma, its effect on elective surgical practice, the poor rate of reimbursement for time spent in trauma management, and the potential medicolegal liability of trauma cases. CONCLUSIONS: These results suggest that there are few surgeons in Ontario who are truly committed to providing care to the injured patient. Strategies to overcome the perceived negative aspects of trauma care must be addressed because a crisis in the availability of surgeons to provide this care seems inevitable. PMID- 7882205 TI - Ten-year experience with a basic technical skills and perioperative management workshop for first-year residents. AB - Teaching technical skills is one of the most crucial tasks of the academic surgeon. The 10-year experience with a psychomotor skills laboratory at the Department of Surgery of the Universite de Montreal is reported. Since 1983, first-year trainees were freed of hospital duties for "a week of surgical techniques" to develop their basic surgical technique and perioperative skills. Cognitive and practical sessions were designed for two groups of 10 residents. Teaching videos, suture boards, biologic substitutes, animal laboratory, round table discussions and formal lectures were the techniques used. Cognitive sessions were designed to provide information on instrumentation, adequate preoperative preparation, general organization of the operating room, intensive care and endoscopy units. The surgical procedures were approved by the local animal ethics committee. The program helped residents achieve surgical dexterity in a less stressful and more controlled manner than in the operating room. Close relationships of the trainees with their peers and teachers were established early helped to improve the operating environment. This program helps junior residents understand the complex world of the operating room and reduces the operative risks related to technique. PMID- 7882206 TI - Learning surgical technical skills. AB - Training issues raised by the recent introduction of laparoscopic surgical techniques led to this analysis of motor-skill learning principles as they apply specifically to the learning of technical surgical skills. The most accepted theories of motor-skill learning are presented, not as opposing views, but as complementary constructs. The behaviourist school of thought's main contribution is the executive routine or knowledge of the steps of a procedure. Schmidt's schema theory and MacKay's node theory suggest that perceptual information may play an important role in the quality of the performance. The conclusions reached from neuropsychologic testing experiments on surgeons are that visuospatial perceptual skills (the ability to represent mentally the physical environment and the movement to be performed) are the major determinants of surgical technical performance. Learners should make use of learning strategies that improve mental representation of a skill and the corresponding anatomy. Specific strategies discussed include imagery, mental practice and a systematic review of performance that focuses on the perceptual feedback received by the learner. PMID- 7882207 TI - Carotid endarterectomy in a vascular fellowship training program: good results with a consistent technique. AB - OBJECTIVE: To find out whether carotid endarterectomy performed by senior residents or vascular fellows in a vascular fellowship program with a uniform technical approach can give results equal to or better than the acceptable standard. DESIGN: A case study with follow-up ranging from 121 to 1369 days. SETTING: A university teaching hospital. PATIENTS: Two hundred and one consecutive patients operated on between May 1989 and June 1993. INTERVENTIONS: Isolated carotid endarterectomy. MAIN OUTCOME MEASURES: Neurologic findings, cardiovascular complications and local wound problems after carotid endarterectomy. RESULTS: There were no deaths, one permanent stroke and two significant deficits from which the patients fully recovered. CONCLUSIONS: Carotid endarterectomy can be performed by senior surgical residents and vascular fellows within a vascular fellowship program, with a perioperative stroke and death rate of less than 1% when a uniform approach is used. PMID- 7882208 TI - Undergraduate surgical education in the twenty-first century. AB - Although the subject of undergraduate surgical education has been debated extensively, especially in the past few years, most of the opinions and decisions made in this field have been those of practising surgeons. In this essay, a medical student's perspective is offered, indicating that if reform is to take place in the field of undergraduate surgical education four basic needs must be filled: increased medical student teaching by faculty members, increased self directed learning in surgical clerkships, a reemphasis of the four basic principles of clinical medicine and a clear definition of the role of the specialist in undergraduate surgical education. PMID- 7882209 TI - Clinical and radiologic effects of diaphyseal stem extension in noncemented total knee replacement. AB - OBJECTIVE: To determine the clinical and radiologic effects of the addition of a diaphyseal stem extension to the tibial component in noncemented total knee replacement. DESIGN: A cohort study. SETTING: A university-affiliated institution specializing in elective orthopedic surgery. PARTICIPANTS: One hundred and twenty one patients with arthritis of the knee underwent noncemented total knee arthroplasty with a diaphyseal stem extension. All agreed preoperatively to prolong postoperative follow-up. Forty-six of the patients had a 100-mm stem extension, 56 had a 50-mm stem extension and 19, who had good bone with no intraoperative micromotion, had no stem extension. One patient died 6 weeks after operation and was excluded, leaving 120 knees available for study. Follow-up was 6 months to 3 years. INTERVENTION: Noncemented total knee replacement with the Tricon II prosthesis. MAIN OUTCOME MEASURES: Clinical effects of the diaphyseal stem extension as determined by the Hospital for Special Surgery rating system and radiologic effects as determined by the Cameron classification. RESULTS: Clinically there was little difference between the three groups, with more than 90% in all groups scoring good or excellent. Radiologically, after elimination of single-zone lucency, both stem-extension groups showed a profound decrease in stem lucency. In patients who had a 100-mm stem extension, 90.9% had type IA lucency and 9.1% had type IB; no type II or type III lucency was seen. There was no correlation between radiologic and clinical results. CONCLUSION: The addition of a diaphyseal stem extension to the Tricon II prosthesis reduces the amount of radiolucency in the tibial component in noncemented total knee replacement. PMID- 7882210 TI - Biaxial total wrist arthroplasty in rheumatoid arthritis. AB - OBJECTIVE: To judge the outcome of total wrist arthroplasty. DESIGN: A retrospective study of 13 patients. SETTING: A university hospital. PATIENTS: Seventeen patients with stage III or IV rheumatoid arthritis of the wrist. Only 13 patients were studied because 3 died and 1 was lost to follow-up. INTERVENTION: Biaxial total wrist arthroplasty (15 procedures). MAIN OUTCOME MEASURES: Clinical assessment and the Hospital for Special Surgery scoring system and radiologic review. RESULTS: Good or excellent results were achieved in all patients after an average follow-up of 54 months. CONCLUSION: Biaxial total wrist arthroplasty is a reasonable treatment in rheumatoid patients when preservation of wrist motion is critical. PMID- 7882211 TI - Skeletal muscle injury induced by ischemia-reperfusion. AB - OBJECTIVE: To study the temporal progression of injury in skeletal muscle after ischemia-reperfusion insult by means of intravital videomicroscopy and nuclear fluorescent dyes. DESIGN: A controlled study in an animal model. SETTING: A vascular research laboratory at a university-affiliated hospital. SUBJECTS: Eight male Wistar rats, for each of which the extensor digitorum longus muscle of the hind limb was exposed and prepared. INTERVENTIONS: Two hours of complete no-flow ischemia followed by 90 minutes of reperfusion in five of the rats; the other three rats acted as controls and underwent the same surgical procedure but not ischemia. During the reperfusion period the fluorescent vital dyes bisbenzimide, which permeates all cells, and ethidium bromide, which permeates cells with damaged membranes, were applied. Recordings to videotape were made with the intravital microscope very 15 minutes during the reperfusion period. MAIN OUTCOME MEASURES: The number of perfused capillaries crossing three straight lines on the video monitor were counted as a measure of microvascular dysfunction. An index of tissue injury was calculated as the ratio of the number of nuclei stained by ethidium bromide to the number stained by bisbenzimide (E/B). The number of stuck and rolling leukocytes and the velocity of the rolling leukocytes were determined in postcapillary venules. RESULTS: The mean number of perfused capillaries (and standard error of the mean) fell from 20.71 (1.64)/mm before ischemia to 11.69 (1.18)/mm during reperfusion in the experimental group but remained constant in the control group. In the experimental group E/B progressed from 0.43 (0.05) at the onset of reperfusion to 0.87 (0.03) at the end of reperfusion, the number of rolling leukocytes increased from a preischemia mean of 4.00 (1.90) to 14.80 (1.30)/1000 microns2, and the number of stuck leukocytes increased from 1.42 (0.20) to 9.20 (0.70)/1000 microns2. The velocity of the rolling leukocytes did not differ between the control and the experimental groups. CONCLUSIONS: Although microvascular perfusion decreased quickly to a constant level after 2 hours of noflow ischemia plus reperfusion, a progressive increase in tissue injury occurred, which may correlate with the number of stuck leukocytes. PMID- 7882212 TI - Streptomycin-loaded bone cement in the treatment of tuberculous osteomyelitis: an adjunct to conventional therapy. AB - Streptomycin-loaded bone-cement (7 g of streptomycin in 40 g of bone cement) beads were used in the treatment of tuberculous bursitis and osteomyelitis of the greater trochanter in a 76-year-old woman. Wound drainage, serum and urine concentrations of streptomycin were measured. For the first 96 hours, the streptomycin levels in the wound drainage ranged from 2932 mg/L to 414.4 mg/L, and in the serum, streptomycin levels ranged from 1.7 mg/L to 13.7 mg/L. The patient recovered without complication and at follow-up 2 years later was free of infection and walking without pain. The authors conclude that the use of streptomycin-loaded bone cement can safely and effectively eradicate mycobacterial tuberculosis osteomyelitis. PMID- 7882213 TI - Laparoscopic splenectomy for massive splenomegaly: operative technique and case report. AB - Although laparoscopic splenectomy is the preferred technique for the elective removal of normal-sized and moderately enlarged spleens, its value in the management of massive splenomegaly has not been defined. A 33-year-old woman with massive splenomegaly was managed by laparoscopic splenectomy. The splenic vessels were embolized preoperatively to reduce operative blood loss. Laparoscopic surgery involved dissection of the suspensory ligaments at the lower pole of the spleen followed by dissection and ligation of all splenic branches near the splenic parenchyma. The operative field was explored manually through a 10-cm long Pfannenstiel incision at the public hairline, and under videoscopic control the remaining structures were safely secured. The spleen was delivered into the pelvis, fragmented and removed in large pieces. The incisions were closed after proper irrigation and laparoscopic inspection of the operative field. Further clinical evaluation is required to determine if the procedure is more efficacious than the open technique for massive splenomegaly. PMID- 7882214 TI - Laparoscopic splenectomy for congenital spherocytosis with splenomegaly: a case report. AB - The traditional method of splenectomy involves a 7- to 10-cm abdominal incision, with its attendant morbidity that includes sepsis. Recently, the laparoscopic technique has been adopted for splenectomy. Many surgeons still believe that laparoscopic splenectomy should be carried out only for idiopathic thrombocytopenia purpura and Hodgkin's disease with a normal-sized spleen. A 16 year-old girl with marked splenomegaly (spleen size for times normal and weighing 600 g) due to congenital spherocytosis underwent laparoscopic splenectomy and retrieval of the spleen through the umbilical trocar site. Preoperative arterial embolization was not used, and the operative blood loss was estimated to be only 250 mL. Her postoperative course was uncomplicated, and she was discharged on the 4th postoperative day. The operative technique is described and the advantages of laparoscopic splenectomy are discussed. PMID- 7882215 TI - Recognition of renal actinomycosis: nephrectomy can be avoided. Report of a case. AB - Nephrectomy is performed for the diagnosis and treatment of renal actinomycosis. A cachectic 62-year-old man with a left renal mass underwent exploration and needle biopsy of the mass. No malignant disease was found. When his condition further deteriorated, the kidney was re-explored. Numerous biopsies intraoperatively finally revealed actinomycosis, so the operation was terminated with preservation of the kidney. Long-term treatment with antibiotics was begun with immediate, marked improvement in the patient's condition. At 1 year the renal mass had almost resolved. This is the first reported case of the diagnosis and treatment of renal actinomycosis without nephrectomy. PMID- 7882216 TI - Surgical education: time for a change? PMID- 7882217 TI - Extragonadal nonseminomatous germ cell tumour with hypercalcemia, masquerading as renal cell carcinoma: a case report. AB - Humoral hypercalcemia secondary to the production of parathyroid hormone-related peptide has been reported to occur in up to 17% of patients with renal cell carcinoma but has been reported only rarely in patients with other genitourinary cancers and never in patients with testicular or extragonadal nonseminomatous cancers. A 54-year-old man is reported who had an extragonadal nonseminomatous germ cell tumour with hypercalcemia that masqueraded as a renal cell carcinoma with metastases. The hypercalcemia was suspected to be humorally mediated. PMID- 7882218 TI - Markedly elevated serum CA 19-9 levels in a case of chronic pancreatitis. AB - Serum levels of carbohydrate antigen (CA) 19-9 exceeding 1000 U/mL are considered highly specific for pancreatic cancer and have not been reported in nonmalignant pancreatic disease. A young man with obstructive jaundice, a serum CA 19-9 level of 2350 U/mL and a mass in the head of the pancreas, seen on computed tomography, was found to have chronic pancreatitis without malignant disease. This case demonstrates that a markedly elevated serum level of CA 19-9 can occur in nonmalignant pancreatic disease and emphasizes the need for a histologic diagnosis of malignancy even if the clinical diagnosis of pancreatic cancer seems certain. PMID- 7882219 TI - Ectopic thyroid gland simulating a thyroglossal duct cyst: a case report. AB - There have been many reports of the inadvertent removal of an ectopic thyroid gland that was mistaken for a thyroglossal duct cyst. The differentiation of these two conditions is extremely important, because inadvertent removal of an ectopic thyroid gland may result in profound hypothyroidism. The authors report the case of a 5-year-old girl with an ectopic thyroid gland in whom the preliminary diagnosis was a thyroglossal duct cyst. They review the embryologic features in the development of an ectopic thyroid gland and discuss an approach to the management of this congenital anomaly. PMID- 7882220 TI - Tuberculous osteomyelitis. PMID- 7882221 TI - Ruptured deep femoral artery aneurysm simulating a soft-tissue sarcoma: a case report. AB - False aneurysms of the deep femoral artery are uncommon. The presentation in the 80-year-old woman described in this case report was unique in that the pseudoaneurysm was subacute; after an initial hemorrhage, compression of the pseudoaneurysm by the deep femoral artery resulted in a large hematoma suggestive of a soft-tissue sarcoma. The recommended management was angiography, computed tomography and magnetic resonance imaging to differentiate between a false aneurysm and a tumour followed by treatment for the vascular lesion. Such an approach will prevent tumour spread and uncontrollable hemorrhage. PMID- 7882222 TI - Spigelian hernias in infants: report of two cases. AB - Spigelian hernia, an uncommon but well-recognized ventral hernia, is rare in children. Two such cases are reported, both on the left side in female infants under 1 year of age. The first hernia, which was repaired when the infant was 7 months old, contained an ovary. Repair of the second hernia, which was diagnosed in the neonatal period, was delayed because of a congenital diaphragmatic hernia requiring urgent repair. The hernia reduced spontaneously and is no longer palpable, suggesting spontaneous closure. A literature review revealed only eight other cases of spigelian hernias occurring in infants less than 1 year of age. Spontaneous closure has not been recorded before. PMID- 7882223 TI - Autotransfusion of shed mediastinal blood in cardiac surgery. PMID- 7882224 TI - Jive fracture of the first rib. PMID- 7882225 TI - Prevention of nausea after laparoscopic cholecystectomy. PMID- 7882227 TI - Who determines quality of life? PMID- 7882226 TI - Free market role in medical care. PMID- 7882228 TI - Expecting miracles, accepting death. PMID- 7882229 TI - Lessons for atherosclerosis research from tuberculosis and peptic ulcer. AB - Knowledge of the causes of a disease is essential to the effective alteration of factors affecting the disease's incidence. The history of the medical understanding of tuberculosis and peptic ulcer shows that we may neglect to consider the contribution of microorganisms to long-term or recurring diseases. The author presents evidence that we may similarly be overlooking the role of microorganisms in atherosclerosis. A collaborative, comprehensive investigation of the role of microorganisms in atherosclerosis is needed to understand the cause of this disease. PMID- 7882230 TI - Variation in length of stay as a measure of efficiency in Manitoba hospitals. AB - OBJECTIVE: To examine the efficiency of Manitoba hospitals by analysing variations in length of stay for patients with similar characteristics. DESIGN: Retrospective study. Multiple regression analyses were used to adjust for patient (case-mix) characteristics and to identify differences in length of stay attributable to the hospital of admission for 14 specific, frequently encountered diagnostic categories and for all acute admissions. SETTING: The eight major acute care hospitals in Manitoba. PARTICIPANTS: Manitoba residents admitted to any one of the eight hospitals during the fiscal year 1989-90, 1990-91 or 1991 92. Patients transferred to or from another institution, those with atypically long stays and those who died in hospital were excluded. OUTCOME MEASURE: Length of hospital stay. RESULTS: The length of stay was strongly influenced by hospital of admission, even after adjustment for key patient characteristics. Excluding the most seriously ill patients and those with the longest stays, approximately 186 beds could potentially have been saved if each hospital had discharged its patients as efficiently as the hospital with the shortest overall length of stay. CONCLUSIONS: A substantial proportion of days currently invested in treating acute care patients could be eliminated. At least some bed closures in Manitoba hospitals could be accommodated simply through more efficient treatment of patients in the remaining beds, without decreasing access to hospital care. PMID- 7882232 TI - Psychiatric illness and psychosocial concerns of patients with newly diagnosed lung cancer. AB - OBJECTIVE: To determine the nature and incidence of psychiatric illness, symptoms of potential psychiatric significance, substance abuse and psychosocial concerns among patients with newly diagnosed lung cancer. DESIGN: Case series. SETTING: Kingston Regional Cancer Centre, a tertiary care facility for ambulatory cancer patients. PATIENTS: Seventy-one consecutive English-speaking patients with recently diagnosed lung cancer undergoing radiotherapy or chemotherapy were asked to participate; 52 of the 57 patients who agreed were available for evaluation. OUTCOME MEASURES: Current and previous psychiatric diagnoses of affective, anxiety and adjustment disorders, and alcohol and tobacco abuse; symptoms of sadness, fear, shock, anger, denial, acceptance, guilt, suicidal ideation, thoughts of death, insomnia, loss of libido, impaired concentration and reduced level of work or interest; psychosocial concerns about family, work and finances; and an impression of coping. RESULTS: At the time of the interview two (4%) of the patients were found to have an affective disorder, none had an anxiety disorder, and six (12%) had an adjustment disorder. Previously, 16 patients (31%) had had an affective or anxiety disorder or both. Two (4%) had had an adjustment disorder following the diagnosis of their lung cancer that had resolved before the interview. At some point in their lives 24 patients (46%) had abused alcohol, and 7 (13%) were currently abusing alcohol. All had smoked, 33 (63%) having been tobacco dependent. Feelings of sadness were expressed by 23 (44%), fear by 15 (29%), anger by 2 (4%), shock by 9 (17%) and guilt by 4 (8%). Seven (13%) had considered suicide, and thoughts of death were reported by 16 (31%). Twenty (38%) were accepting of their diagnosis, and 5 (10%) expressed optimism. Twenty-seven (52%) had insomnia, which was reported to be severe by 15 (29%). Loss of libido was reported by 25 (48%) and was severe in 14 (27%). Difficulty concentrating was reported by 10 (19%) and a reduced ability to work or loss of interest by 17 (33%). Fifteen patients (29%) were concerned about their families and 4 (8%) about work or finances. Most (41 [79%]) had good family support, and 23 (44%) found support in religion. Seven patients (13%) seemed to be coping poorly. CONCLUSIONS: Although psychiatric illness was infrequent, symptoms of potential psychiatric significance and psychosocial concerns were common in this patient population. Attention to these symptoms and concerns should be addressed in a systematic and effective way by all health care professionals and agencies planning the care of patients with lung cancer. PMID- 7882231 TI - Variation in orthopedic surgeons' perceptions of the indications for and outcomes of knee replacement. AB - OBJECTIVE: To determine the agreement among orthopedic surgeons' indications for knee replacement, their perceptions of the usefulness of various treatments for osteoarthritis of the knee and their expected outcomes of knee replacement, and to determine the relation between these opinions and the number of knee replacement procedures performed by individual surgeons. DESIGN: Survey. SETTING: Ontario. PARTICIPANTS: All 392 orthopedic surgeons in the province. Of the 325 practising traceable surgeons 234 (72.0%) responded. OUTCOME MEASURES: Indications for knee replacement, perceived usefulness of treatments for osteoarthritis, perceived outcomes of knee replacement and number of knee replacement procedures performed by individual surgeons. RESULTS: The respondents disagreed on how 20 of 34 patient characteristics affected their decision to perform knee replacement surgery. They also disagreed on the usefulness of seven of eight treatments for arthritis of the knee. The respondents demonstrated variation in their expected outcomes of knee replacement. The surgeons who performed more procedures judged, on average, the outcomes to be better and to have fewer complications than the surgeons who performed fewer procedures. CONCLUSIONS: Orthopedic surgeons demonstrated disagreement about some of the indications for knee replacement, the usefulness of treatments for arthritis of the knee and the perceived outcomes of knee replacement. The areas of greatest disagreement should be the focus of future research and the development of practice guidelines. PMID- 7882233 TI - Physicians targeted as abortion debate in US turns violent. AB - The last 2 years have marked a dramatic escalation in the level of abortion related violence in both Canada and the US. Two physicians and two clinic workers have been murdered since 1993, and last November the violence may have moved north of the border with the shooting of Dr. Garson Romalis in Vancouver. Milan Korcok looks at the threats facing American abortion clinics and the people who work in them, and discusses steps that have been taken to protect them. He warns that the violence that has plagued the US because of this issue may now be moving across the border to Canada and other countries. PMID- 7882234 TI - Saying goodbye to Canada's single-payer system. AB - Cost shifting, in which governments transfer the cost of certain health care services to patients or private insurance companies, is increasing rapidly, and Dr. Christopher Carruthers thinks it will spell an end to Canada's single-payer system. The signs are already there: the private sector is offering more services and employers are keeping a closer eye on the health care system as they begin to pay a bigger share of the costs. The result, says Carruthers, is that government influence is bound to diminish as the private sector tries to fill voids created by governments that are trying to live within their fiscal means. PMID- 7882235 TI - New prenatal screening procedures raise spectre of more "wrongful-birth" claims. AB - Last year a Winnipeg couple whose baby was born with profound disabilities initiated a lawsuit against their doctor alleging that they were not adequately informed of the results of a prenatal blood test. The case was later settled out of court. Although the legal basis of the suit was negligence, the damages claimed related to the controversial concepts of "wrongful birth" and "wrongful life". As more and more prenatal tests are developed, physicians should familiarize themselves with the ways informed consent pertains to prenatal testing. PMID- 7882236 TI - Core and comprehensive health care services. PMID- 7882237 TI - Australia's Flying Doctors re-evaluate medical services needed in the outback. AB - Australia's fabled Royal Flying Doctor Service recently undertook a soul searching evaluation of its structure, operations and goals. Although there are no plans to stop providing emergency medical services to the residents of the outback, the service may refocus efforts on health promotion and prevention, since 75% of its work involves nonemergency care. Cost efficiency, the key phrase for health care around the globe, will be another goal. PMID- 7882238 TI - Use of filters to treat visual-perception problem creates adherents and sceptics. AB - Patients who think they have a visual-perception dysfunction known as scotopic sensitivity-Irlen syndrome have trouble reading and may experience almost constant headaches. Some find they are helped by coloured filters developed by a California researcher, Helen Irlen, who published a book on the subject called Reading by the Colors. Although Irlen has been criticized for not publishing scientific proof of the validity of her theories, her techniques have found some support, including some within the medical community. PMID- 7882239 TI - The CNS and nursing informatics. PMID- 7882240 TI - In a changing world: database to keep the pace. AB - A database to manage health care information can be an especially useful tool for the CNS. Systematic management of information is important in the multifaceted role characteristic of the CNS's scope of practice. The CNS not only provides theoretically sound creative care to patients and serves as a role model to nursing staff, but also monitors and substantiates the quality and effectiveness of care delivered. To do this, the CNS participates in research activities and synthesizes and uses research findings. These aspects of professional practice require collection and analysis of information that could be facilitated by the use of a database. The purposes of this article are to introduce some basic concepts of database and its relevance and contribution to the CNS, discuss issues inherent in setting up a database, and provide guidelines for CNSs who are considering using a database in their clinical practice. PMID- 7882241 TI - Family-centered nurse coordinator-early childhood intervention: development and implementation of the CNS role. AB - Professional conceptualization of a relatively new role, entitled family-centered nurse coordinator-early childhood intervention by the author, as developed and implemented by the parent-child CNS is presented in this article. Three essential perspectives are discussed: (1) clarification of the role, (2) major assumptions underlying the role, and (3) use of the nursing process as a framework for successful role implementation. PMID- 7882242 TI - CNS: thriving or heading for extinction? PMID- 7882243 TI - Florence Nightingale: a CNS role model. PMID- 7882244 TI - Continuity of care through nursing case management of the chronically ill child. AB - In the care of the chronically ill or disabled child, continuity of care between hospital and home must be prompt and continuous. In our myelomeningocele clinic, continuity of care is maintained through a nursing case management system. Our definition of case management is derived from the definition of service coordination made by the Ohio State Bureau for Children with Medical Handicaps. The service coordinator is a CNS who works for health care coordination by bringing together all health care services that are needed for a child with a disabling condition. We describe the aspects of that care coordination, including a thorough definition of our nursing case management process. PMID- 7882245 TI - CNS roles in implementation of a differentiated case management model. AB - As advanced nursing practitioners and consultants, CNSs are leaders in affecting changes in nursing practice. During implementation of Primm's model of differentiated case management at Community Memorial Hospital, Menomonee Falls, Wisconsin, the CNSs enacted the roles of implementation consultant, researcher, direct care provider, educator, and performance and project evaluation consultant. The CNSs were committed to initiating and maintaining change, and facilitating momentum to incorporate the differentiated levels of staff nurse practice. We describe CNS roles in this process as well as outcomes seen after implementation of differentiated case management. PMID- 7882246 TI - MEDWatch: medical products reporting program. PMID- 7882247 TI - Research in clinical practice and practice in clinical research. PMID- 7882248 TI - CNS as unit-based case manager. AB - Patient satisfaction, patient-perceived quality of life, and nurse satisfaction were compared before and after implementation of nursing case management on a 36 bed medical unit in a southeastern acute care hospital. In this quasi experimental pre- and postintervention study, 50 adult oncology patients were surveyed. CNSs as unit-based case managers planned, coordinated, and facilitated care that was delivered by registered nurses, licensed practical nurses, and nursing assistants. As measured by the LaMonica/Oberst Patient Satisfaction Tool, patient satisfaction showed a statistically significant increase six months after implementation of nursing case management. Neither job satisfaction of nurses nor patient-perceived quality of life showed significant improvement. PMID- 7882249 TI - Evaluating quality of care using modular nursing on a multispecialty unit. AB - The purpose of this study was to examine performance outcome measures of nurses who work on a general medical unit and those who work on specialized or modular units. A sample of 82 nurses were reassigned to patients in either specialty modules or a general medical unit. Findings suggest that large nursing units staffed according to modular groups based on common diagnosis may improve nursing care quality. Modular nurses assigned to patients on a general medical unit made more medication errors, charted nursing interventions less frequently, and were less likely to provide prompt PRN medication administration. Of concern is the care provided to chronically ill; elderly clients not admitted to a predetermined specialty module received the poorest nursing care. We support development of specialty nursing modules to replace large, general medical units, it does not measure the impact of retention, cost, or other key variables on nurse staffing. We suggest that large medical units be divided into specialty modules and that staff rotation to general medical units be minimized. PMID- 7882250 TI - When industry courts your clinical research skills, should you collaborate? AB - Hospital/industry collaboration is as yet rare in Canadian nursing research. Dupont Canada Inc. invited this research team to become one of four sites taking part in a study of decubitus ulcers in intensive care unit patients. The project was regarded as an opportunity to study an important nursing problem. Collaboration involved a multicenter meeting to plan the research with personnel from the four sites and data collection on the incidence of pressure sores in intensive care unit patients. Industry contributed funding for the project, work on the overall research design, coordination of the sites, and data analysis. The hospitals contributed clinical knowledge, access to the patients, and skilled nurses to collect skin care data. The authors have gained from the collaboration, as has industry. In this article, we review the process, problems, and benefits of collaboration with industry and provide recommendations for nurses getting involved in hospital/industry collaborative research. PMID- 7882251 TI - Understanding costs. PMID- 7882252 TI - Outcome standards. PMID- 7882253 TI - Sharing your research project: a continuing education approach. AB - CONTINUING EDUCATION PROGRAMS as a practical approach for the CNS to share research results are described in this article. Strategies for planning and implementing this approach are shared, a case example is provided, and benefits to the program are described. PMID- 7882254 TI - Staff nurse preceptors: a program they "own". AB - Application of a change theory model to develop a competency-based orientation (CBO) program managed by staff nurse preceptors resulted in preceptor satisfaction, improved patient outcomes, and a more effective, efficient orientation program. After assessing the group using Hersey and Blanchard's framework, the CNS selected change strategies to implement the CBO, including: (1) helping staff nurses to redefine problems with current orientation procedures; (2) anticipating and overcoming their objections to CBO; (3) bolstering their confidence in a trusting, accepting environment; (4) motivating them as preceptors; and (5) providing direction, models, and explanations. These strategies helped preceptors accept and feel an "ownership" of the new program, resulting in many outcomes in the system. Veteran staff nurses gradually assumed ownership for individual orientees and managing orientation activities in the CBO. Rather than precepting individual orientees, the CNS assumed responsibility for establishing CBO and helping preceptors maximize their potential. PMID- 7882255 TI - Health care reform: an international perspective. PMID- 7882256 TI - Applying Benner's model to school nursing of multiple handicapped children. AB - The role of the school health nurse has become more complex in recent years due to public policy changes. The focus of this article is on changes in school health nursing since enactment of Public Law 94-142, the Education for All Handicapped Children Act, which places medically complex and multiply handicapped children in the public school system. The changing character of school health nursing increases the need for the advanced practice nurse (APN) to use nursing theories to guide nursing decisions. In this article, Benner's Model of Expert Practice is used by the APN in the challenging setting of school health nursing. A case study is included to describe how an APN can use this model to promote optimal functioning in a child with multiple handicaps while helping the child and family transition through developmental stages. PMID- 7882257 TI - Cultural differences: what can we learn? PMID- 7882258 TI - Ethics in Japanese health care: a perspective for clinical nurse specialists. AB - Bioethical issues relevant to nurses in Japan are described in this article. Significant Japanese values and behavior patterns, the impact of religion on ethical concerns, patient and family roles in illness, and relationships with the physician are described. Within this context, Japanese nursing involvement in ethics and selected ethical issues are explored with examples. PMID- 7882259 TI - Alcoholism in homeless veterans: a historical overview. AB - The department of Veterans Affairs uses a variety of approaches to assist homeless veterans suffering from alcoholism, including outreach and domiciliary programs. The history of alcoholism and homelessness is discussed in this article and characteristics of homeless veterans are delineated. Cultural considerations, treatment options, and the role of the CNS working with this population are presented. Implications for further research are included. PMID- 7882260 TI - Dollars and sense. part II: appropriate use of pressure ulcer prevention and management products. PMID- 7882261 TI - Graduate education and health care. PMID- 7882262 TI - Testing practice models. PMID- 7882263 TI - Collaborative discharge planning: nursing and social services. AB - Discharge planning impacts hospital costs and patient outcomes. The purpose of this study was to determine the effects of a structured discharge planning program using collaboration between the CNS and the social worker. The quasi experimental study used a sample of 64 elderly patients. The experimental group (n = 29) had discharge planning directed through collaboration by a CNS and a social worker. After discharge, patients were contacted by telephone about satisfaction and services received. Charts were reviewed for information about length of stay, readmission, and documentation. Data analysis revealed that patients involved in collaborative planning were more satisfied, had a shorter length of stay, had fewer readmissions, and received a higher rate of indicated postdischarge services. Documentation was not significantly affected, except in the area of patient teaching, which was lower in the experimental group. Based on these findings, the collaborative model offers nurse administrators a way to improve outcomes for patients and the organization. PMID- 7882264 TI - Difference in length of stay with care managed by clinical nurse specialists or physician assistants. AB - The purpose of this study was to examine the relationships among patient length of stay, complications, and type of care manager (clinical, nurse specialists [CNSs] vs. physician assistants [PAs]). A descriptive comparison of two groups was performed. Data were collected using a retrospective chart audit of 105 randomly selected patients who had undergone elective coronary artery bypass surgery for the first time between 1991 and 1993. Group 1 comprised patients for whom PAs and cardiac surgeons co-managed postoperative care. Group 2 comprised clients whose care was co-managed by CNSs and cardiac surgeons. Complication rates were similar between the two groups. Findings indicated that the CNS managed group had a statistically significant shorter length of stay. Results suggested that care managed by CNSs can decrease length of stay, when compared with care managed by PAs. PMID- 7882265 TI - The coming of acute care nurse practitioners. PMID- 7882266 TI - A call for compassion for prisoners in Lewisohn's "The Children of the State". PMID- 7882267 TI - Self-governance: an evolving process. PMID- 7882268 TI - Collegial model for clinical nurse specialists: theoretical perspective. AB - Organizationally based CNSs function in a wide variety of management structures. A review of the literature suggests that the steady-state career orientation typifies CNSs and is therefore compatible with the application of self-management strategies. With this in mind the Long Beach Memorial Medical Center Collegial Model for Clinical Nurse Specialists was developed and components were defined as a self-governing strategy for CNSs within a complex tertiary medical center. PMID- 7882269 TI - Collegial model for clinical nurse specialists: implementation. AB - CNSs have typically reported to a variety of administrative or management positions within organizational structures. The Collegial Model for Clinical Nurse Specialists was developed and operationalized as a self-governing strategy for CNSs within a multihospital medical center. Implementation process of this model, including the driving forces, obstacles encountered, and strategies for operationalization are addressed in this article. PMID- 7882270 TI - Patient-focused or patient-driven care? PMID- 7882271 TI - Psychosocial needs of family members of liver transplant patients. AB - Recent literature is beginning to reflect the importance of psychosocial needs of liver transplant patients, examining functional outcome, quality of life, daily living, and psychiatric and neurocognitive outcome. Little attention has been paid to the psychosocial needs of the liver transplant patient's family or significant other. Family members, along with the patient, must cope with disease chronicity, an uncertain organ donor waiting period, role reversal, a protracted postoperative hospital course, and a complicated medical regimen after discharge. Consequently, demands on time, energy, finances, and relationships can strain an already stressed family structure. Psychosocial needs of the liver transplant patient's family are discussed in this article, including aspects of chronic disease, the transplant evaluation, the waiting period, the immediate postoperative period, and long-term adjustment and recovery. Nursing interventions to facilitate effective coping strategies are suggested. Gaps in the existing literature are identified and suggestions for future research are made. PMID- 7882272 TI - A CNS in a rural community. PMID- 7882273 TI - Pathologic analysis of the National Surgical Adjuvant Breast Project (NSABP) B-17 Trial. Unanswered questions remaining unanswered considering current concepts of ductal carcinoma in situ. PMID- 7882274 TI - Human malignant melanoma. A genetic disease? AB - BACKGROUND: Human hereditary malignant melanoma, comprising 5% of all cases of malignant melanoma, occurs in association with other malignancies, predominantly in families with dysplastic nevus syndrome. Additionally, higher incidences of malignant melanoma have been reported in individuals with genetic disorders such as ataxia telangiectasia and xeroderma pigmentosum. The results and observations as reported in the literature on the involvement of oncogenes and chromosomal aberrations in the development of malignant melanoma are reviewed and compared with the authors' own experimental and clinical experience. RESULTS: Numerous chromosomal regions, as on chromosomes 1 and 9, were altered. The long arm of chromosome 6 was affected in 60% of melanomas. Introduction of a normal copy of chromosome 6 resulted in loss of tumorigenicity in vitro. True melanoma genes were evident in two animal models: the Sinclair swine and the teleost fish Xiphophorus. In the Xiphophorus system, the crossing-conditioned elimination of a tumor suppressor gene led to the uncontrolled activity of a dominantly acting oncogene in certain hybrids. The causative oncogene, Xmrk, encodes a receptor tyrosine kinase closely related to human epidermal growth factor receptor (EGFR). Among the numerous studied human oncogenes, mutations in the extensively investigated ras family are the result rather than the cause of malignant transformation. High expression of nuclear oncogenes simply may be a common feature of rapidly dividing cells. The receptor tyrosine kinase EGFR may be involved in late stage melanoma; the human exon with homology to Xmrk shows elevated transcription levels in 80% of human melanoma metastases. Deletions of the tumor suppressor gene MTS 1 may be important for melanoma formation, whereas deletions of p53 appear to be of minor relevance. CONCLUSION: Scientific progress in treating and diagnosing malignant melanoma will largely depend on experimental approaches to define relevant genetic changes by functional analysis rather than descriptive phenomenology and correlative observations. PMID- 7882275 TI - Sequential methotrexate, 5-fluorouracil (5-FU), and high dose leucovorin versus 5 FU and high dose leucovorin versus 5-FU alone for advanced colorectal cancer. A multi-institutional randomized trial. AB - BACKGROUND: The primary objective of this study was to compare the single biochemical modulation of 5-fluorouracil (5-FU) and leucovorin with that of the double-biochemical modulation of methotrexate and leucovorin. Because of the Martin et al. study in which an experimental model showed similar effects of 5-FU at maximum tolerated doses to the modulation with leucovorin at standard doses, a third treatment arm of 5-FU alone was also studied. METHODS: A randomized trial was performed using a 500-mg/m2 intravenous (i.v.) 1-hour infusion of methotrexate, and 12 hours later, a 600-mg/m2 i.v. bolus of 5-FU plus a 200-mg/m2 i.v. 1-hour infusion of leucovorin (MFL) every 2 weeks versus 5-FU plus leucovorin at an equal dose and schedule (FL), versus a 1200-mg/m2 i.v. dose of 5 FU every 2 weeks. Of 186 patients included in the study, 178 were evaluable. RESULTS: In a preliminary analysis with 94 evaluable patients, two significant statistical differences were shown. First, the toxicity rate of the 5-FU--alone (F) treatment arm was higher than that of the other arms (MFL vs. F, P = 0.0002; FL vs. F, P = 0.00001). Second, the median survival was worse in the F treatment arm with a rate of 12.6 months for the MFL and FL arms and 7.5 months for the F arm (P < 0.05). Considering these results, the F treatment arm was discontinued. The final results included 70 evaluable patients for MFL and 74 patients for FL. No difference was found in the distribution of prognostic factors. The response rates were 25.7% for MFL (95% CI, 16-37.5) and 14.8% for FL (95% CI, 7.6-25), (P = 0.1). The median survival was 14.3 months for patients treated with MFL and 12.3 months for those treated with FL. The hematologic toxicity was mild, with no grade 3/4 leukopenia in either treatment arm. The major nonhematologic toxicity in the MFL and FL treatment arms was ocular; nongrade 3/4 diarrhea also was observed. CONCLUSIONS: The results of MFL double-biochemical modulation failed to show a significant statistical difference from that of single-biochemical modulation for this dose and schedule. PMID- 7882276 TI - Arterial-injection chemotherapy for hepatocellular carcinoma using monodispersed poppy-seed oil microdroplets containing fine aqueous vesicles of epirubicin. Initial medical application of a membrane-emulsification technique. AB - BACKGROUND: Iodized poppy-seed oil (IPSO) has a property of depositing itself selectively in the cells of hepatocellular carcinoma (HCC). A mixture of anticancer agents and IPSO has been used widely because IPSO accumulates in tumors, but its usefulness appears limited because the anticancer agents become separated easily from IPSO and do not remain in the tumor. The authors prepared a long term inseparable, water-in-oil-in-water emulsion (W/O/W) for use in arterial injection therapy for patients with HCC and evaluated its clinical usefulness. METHODS: The W/O/W was prepared by a membrane-emulsification technique using a controlled pore glass with 10.6-microns pores. From December 1992 to January 1994, the W/O/W containing 8-60 mg of epirubicin was applied to the hepatic arterial-injection therapy for 21 patients with HCC to determine its antitumor and side effects. RESULTS: After arterial infusions with W/O/W, an evident antitumor effect was observed in all 13 patients treated with W/O/W containing 40 mg or more of epirubicin with or without gelatin-sponge particles used simultaneously. In the group treated with the W/O/W containing a high dose (40 mg or more) of epirubicin, even though the gelatin-sponge particles were not used, tumor size was reduced in six of seven patients, and a 50% or greater decrease of initial alpha-fetoprotein (AFP) levels within 14 days was observed in all four patients who showed abnormal levels of serum AFP before treatment. One partial necrosis and two complete necroses of three resected tumors were confirmed histopathologically. Fever (in all patients), nausea (in two), pain in the right upper quadrant of the abdomen (in two), and slight cough (in one) were noted as minor side effects. CONCLUSIONS: To the authors' knowledge, this is the first clinical trial using this emulsion prepared by the membrane-emulsification technique. Emulsification using a fine-pore glass membrane of equal pore size (i.e., controlled-pore glass membrane) is a new technique for preparing lipid microdroplets of equal size (monodispersed) containing aqueous fine microdroplets to form W/O/W: This technique of chemoembolization can be used to treat patients with HCC. PMID- 7882277 TI - Tissue-type plasminogen activator predicts endocrine responsiveness of human pancreatic carcinoma cells. AB - BACKGROUND: Estrogen receptor (ER) has been found in human pancreatic carcinoma, but the potential benefit of endocrine therapy never has been assessed adequately. The aim of this study was to determine whether the presence of ER can be used as an indicator of hormone responsiveness, and whether modulation of tissue-type plasminogen activator (t-PA) by ER can identify hormone-responsive pancreatic carcinomas. METHODS: The authors investigated ER status and hormonal regulation of t-PA in nine human pancreatic carcinoma cell lines, AsPC-1, BxPC-3, Capan-1, Capan-2, Hs-700T, Hs-766T, MiaPaCa-2, PANC-1, and SUIT-2. Furthermore, to examine whether estrogen dependency of t-PA production in pancreatic carcinoma cells correlated with responsiveness to endocrine therapy, the in vivo effects of various endocrine agents on the growth of the nine pancreatic cell lines transplanted into nude mice were examined. RESULTS: In a 17 beta-estradiol (E2) binding assay, three of the nine pancreatic carcinoma cell lines (BxPC-3, Capan 2, and MiaPaCa-2) contained measurable levels of estradiol binding sites in vitro and in vivo using tumors transplanted into nude mice. Although t-PA was present in the culture medium in eight of the nine pancreatic carcinoma cell lines (not in Hs-700T), t-PA production was regulated by estrogen via an ER system in vitro only in the Capan-2 cell line. E2 injection into tumor-bearing mice showed acceleration of tumor growth only in Capan-2 tumors. Administration of a competitive ER antagonist, toremifene, and a luteinizing hormone-releasing hormone analogue, leuprorelin acetate (LEU), to Capan-2-bearing mice significantly reduced the rate of tumor growth, although there was no actual shrinkage of tumor mass. These agents failed to exert any antitumor effect on the other eight pancreatic cell lines. Although aromatase inhibitors, CGS 20267 and vorozole did not modify the in vivo growth of the nine pancreatic carcinoma cell lines significantly, the combined use of aromatase inhibitors with LEU exhibited a synergistic antitumor effect on Capan-2-bearing mice. Medroxyprogesterone acetate treatment significantly reduced the tumor volume of Capan-2 and also caused delayed growth in two other cell lines, AsPC-1 and MiaPaCa-2. CONCLUSIONS: The estrogen dependency of t-PA production may clarify the functional state of ER in human pancreatic carcinoma cells. This finding may aid in planning endocrine therapy for patients with this lethal cancer. PMID- 7882278 TI - Non-Hodgkin's lymphoma of the sinonasal tract. A clinicopathologic and immunophenotypic study of 120 cases. AB - BACKGROUND: Non-Hodgkin's lymphomas (NHLs) of the sinonasal tract are uncommon neoplasms that can be morphologically difficult to distinguish from destructive nonneoplastic processes or other malignant neoplasms in this site. METHODS: From the files of the Otolaryngic Tumor Registry-Armed Forces Institute of Pathology from 1965 to 1992, 120 cases of NHL involving the sinonasal tract were selected for which clinical records and paraffin-embedded tissue blocks were available. The histologic features and immunophenotypic findings of each patient were examined, and follow-up data were obtained for 66 (55%). RESULTS: The ratio of males to females was 1.35:1, and the ages ranged from 3 to 94 years (median, 59 years). Sixty percent of the cases of NHL occurred in the patients' sixth to eighth decades of life. Clinical presentations varied according to histologic type. The low grade lymphomas presented with a nasal cavity or paranasal sinus mass associated with obstructive symptoms. The high grade lymphomas were more likely to present with aggressive signs and symptoms including nonhealing ulcer, cranial nerve manifestations, facial swelling, epistaxis, or pain. Of note, the high grade B-cell lymphomas tended to present with soft tissue or osseous destruction, particularly of the orbit with associated proptosis, whereas the T cell lymphomas were associated with nasal septal perforation and/or destruction. Sites of disease included the nasal cavity, one or more paranasal sinuses, or multiple regions within the sinonasal tract. Of patients who received adequate follow-up, nodal and extranodal dissemination were identified in a limited number (n = 11). Nodal dissemination occurred in cervical and axillary lymph nodes. Extranodal sites of involvement included the larynx, skin, liver, uvula, kidney, breast, lacrimal gland, testis, and prostate gland. There was a wide spectrum of morphologic types of lymphoma, classified according to the Working Formulation. Immunophenotypic analysis on paraffin embedded tissue sections of all patients demonstrated a B-cell to T-cell ratio of 1.18:1. Treatment primarily included radiotherapy and chemotherapy. Follow-up information was available for 66 (55%) patients ranging from 1 to 16 years (median, 3 years). Of these 66 patients, 24 (36.4%) died of disease, 17 (25.7%) are alive without disease, 13 (19.7%) are alive with disease, and 12 (18.2%) are dead of unrelated or unknown causes. CONCLUSIONS: Non-Hodgkin's lymphomas of the sinonasal tract are heterogeneous diseases that can be clinically aggressive. The frequency of these lymphomas in the United States cannot be estimated accurately because all of our cases were of histologic slides submitted for consultations. There appears, however, to be a slight B-cell predominance in this population that previously has been observed, unlike in South America and Asia where the majority of cases have a T-cell phenotype. PMID- 7882279 TI - Multiple genetic lesions in laryngeal squamous cell carcinomas. AB - BACKGROUND: To understand the molecular pathogenesis of laryngeal squamous cell carcinomas (LSCCs), this study investigated the involvement of various protooncogene loci (bcl-1, int-2, c-erbB-1, c-myc, ras) and the p53 tumor suppressor gene in 18 patients with LSCC (15 at clinical presentation, 3 in clinical relapse). METHODS: For all patients, the mutations affecting the p53 and the H-, K-, and N-ras genes were evaluated by polymerase chain reaction (PCR), single-strand conformation polymorphism, and the direct sequencing of PCR amplified fragments. The bcl-1, int-2, c-erbB-1, and c-myc loci of 15 patients were investigated using Southern blot analysis. RESULTS: A mutation of the p53 gene was detected in 5/18 patients (approximately 28%), bcl-1 locus amplification in 4/15 (approximately 26%), c-erbB-1 locus amplification in 2/15 (approximately 13%), and c-myc locus amplification in 1/15 (approximately 6%). The simultaneous presence of more than one genetic lesion was observed in four patients; two showed int-2/bcl-1 coamplification, and two int-2/c-erbB-1 coamplification, one of whom also showed a p53 gene mutation. A novel p53 mutation involving the splice acceptor site of exon 6 was detected in one patient. Two of the five patients positive for p53 mutations had clinical relapses of primary tumors. bcl 1 locus amplification only was observed in patients with lymph node metastases (4/6). All but one of the patients with molecular genetic lesions showed a peculiar infiltrating pattern. CONCLUSIONS: Overall, these results show that alterations of known protooncogenes and the p53 tumor suppressor gene are involved in a large proportion of LSCCs (11/18; approximately 60%) and may suggest that distinct molecular pathways occur in the pathogenesis of these tumors. PMID- 7882280 TI - Prophylactic cranial irradiation in limited-stage small cell lung cancer. AB - BACKGROUND: The role of prophylactic cranial irradiation (PCI) for patients with limited-stage small cell lung cancer (LSSCLC) remains a controversial issue. This study evaluated PCI in patients with LSSCLC who achieved a complete response to initial chemotherapy. METHODS: A retrospective case study of all nonprotocol patients with LSSCLC examined at our institution from 1982 to 1990 was performed. Of the 67 nonprotocol patients who were treated with combination chemotherapy (cyclophosphamide-based) and thoracic radiotherapy during those years, 43 achieved a complete response. Twenty-four patients received prophylactic cranial irradiation (PCI+) (25-36 Gy in 10-16 fractions), and 19 did not (PCI-) at the physician's or patient's discretion. RESULTS: The distribution of prognostic factors between the PCI+ and PCI- groups was well balanced. Of the PCI+ patients, the 2-year actuarial freedom from relapse in the central nervous system was 93% versus 47% for the PCI- patients (log rank analysis, P = 0.001). An initial central nervous system relapse developed in 2 of the 24 PCI+ patients as the only site of failure versus 7 of 19 PCI- patients (P = 0.003). The 2-year actuarial overall survival was 50% for the PCI+ patients versus 21% for the PCI- patients (P = 0.01). The addition of prophylactic cranial irradiation was the only significant factor contributing to an improvement in time to central nervous system relapse and survival for the PCI+ patients. There were five patients alive at the time of this report, and all received prophylactic cranial irradiation. None had cognitive or neurologic impairment. CONCLUSIONS: Prophylactic cranial irradiation may contribute to improved survival in patients with LSSCLC who achieve a complete response after chemotherapy and thoracic radiation therapy. PMID- 7882281 TI - Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) Protocol B-17. Intraductal carcinoma (ductal carcinoma in situ). The National Surgical Adjuvant Breast and Bowel Project Collaborating Investigators. AB - BACKGROUND: Controversy exists concerning the natural history of ductal carcinoma in situ (DCIS) of the breast, including its pathologic expression and treatment. This controversy has been fostered largely by the retrospective nature and limited sample sizes of extant studies. METHOD: Resolution of some of these issues was attempted by analyzing the pathologic features of 573 examples of DCIS obtained from a larger cohort of 790 women with DCIS enrolled in Protocol B-17 of the National Surgical Adjuvant Breast Project. This prospective randomized clinical trial was performed to assess the efficacy of local breast irradiation to reduce the incidence of second ipsilateral breast tumors (IBT) after lumpectomy. RESULTS: Tumor and patient characteristics, including significantly less IBT for those treated by lumpectomy and irradiation than lumpectomy alone, were almost identical for the subset comprising this analysis and the total B-17 cohort reported previously. The presence of moderate/marked comedo necrosis, which was evaluated as an independent parameter rather than as a specific histologic type of DCIS and uncertain/involved lumpectomy margins were the only statistically significant independent predictors of IBT for patients treated by lumpectomy as well as irradiation. The latter markedly reduced the annual hazard rates for the IBT associated with these indicators. CONCLUSIONS: Although not an endpoint of this study, the authors' findings suggest that the beneficial effect of irradiation in reducing IBT after lumpectomy for DCIS occurs with small (< 1.0 cm.) and larger lesions. Moderate/marked comedo necrosis and uncertain/involved lumpectomy margins represent independent predictors of IBT. PMID- 7882282 TI - Immunohistochemical detection of HER2/neu in patients with axillary lymph node negative breast carcinoma. A study of epidemiologic risk factors, histologic features, and prognosis. AB - BACKGROUND: Numerous studies have examined the prognostic significance of HER2/neu (HER) expression in patients with axillary lymph node negative breast carcinoma. Although some investigations suggest that the presence of the altered expression of HER is prognostically unfavorable, the subject remains controversial. This study explores the interaction of HER with three aspects of axillary lymph node negative breast carcinoma: epidemiologic risk factors, tumor histopathology, and prognosis. METHODS: Immunohistochemical staining for HER was performed on 10% formalin fixed paraffin embedded primary carcinomas from 440 patients with negative axillary lymph nodes with a median follow-up of 119 months. RESULTS: The immunohistochemical expression, or lack thereof, of HER did not prove to be prognostically significant in this group of patients with axillary lymph node negative breast carcinoma. There was also no consistent association with epidemiologic risk factors. The most striking results concerned the relationship of HER to histopathologic features of the carcinomas. Medullary carcinoma differed from other tumor types because it was HER(+) substantially less often (10%) than were other ductal (49%) or lobular (43%) carcinomas. CONCLUSION: The results obtained in this study suggest that the immunohistochemical demonstration of HER is not a reliable prognostic indicator for patients with axillary lymph node negative breast carcinoma. This marker was not associated with major epidemiologic risk factors; however, there was a significant correlation between HER and the phenotypic features of breast carcinoma because medullary carcinoma is rarely HER(+). Although the associations may not be a strong enough basis for refining the classification of breast carcinoma, they could be useful for diagnosing individual patients. The changes in HER that are detectable by the immunohistochemical methods used in this study probably do not occur in the earliest stages of mammary carcinogenesis. PMID- 7882283 TI - Mutant p53 protein overexpression is associated with poor outcome in patients with well or moderately differentiated ovarian carcinoma. AB - BACKGROUND: It has been shown that the p53 gene is mutated in 30-80% of ovarian carcinomas and that the genetic alterations most often manifest as an accumulation of mutant p53 protein in tumor tissue. The prognostic significance of these findings for patients with ovarian cancer, however, must be established clearly. METHODS: Mutant p53 protein in 90 consecutive epithelial ovarian carcinomas was quantitatively analyzed using a time-resolved immunofluorometric procedure. In contrast to immunohistochemical techniques, this method uses two anti-p53 antibodies. The Cox model was used to evaluate the strength of the associations between the prognostic markers and disease relapse or death at univariate and multivariate levels. Kaplan-Meier survival curves were calculated for patients who were p53-positive or negative and for subgroups with a different clinical stage, histologic grade, or residual postsurgical tumor. RESULTS: The positivity rates for p53 included 1/21 (5%) with Stage I disease, 1/6 (17%) with Stage II, 29/51 (57%) with Stage III, and 8/12 (67%) with Stage IV (total = 39/90, 43%). Patients with p53-negative tumors had a significantly longer disease free survival than did patients with p53-positive tumors (P = 0.03); these results were similar for overall survival (P = 0.06). Multivariate analysis revealed that the presence of postsurgical residual tumor was the only predictor significantly associated with poor patient outcome. However, when patients were divided into groups based on histologic grade, patients with well (G1) and moderately (G2) differentiated tumors had a significantly higher risk of cancer relapse and death if mutant p53 protein was present in their tumors compared with patients who were negative for mutant p53 protein (< 0.01). CONCLUSIONS: The immunofluorometric measurement of mutant p53 protein accumulation in epithelial ovarian carcinomas of a low histologic grade was associated significantly with an increased risk for cancer relapse and death. A similar trend also was suggested for early stage disease and in the absence of residual tumor after surgery. These increased risks, however, were not found for patients with high grade or advanced stage cancer or for those with residual tumor. To the authors' knowledge, this is the first report suggesting that p53 tumor protein accumulation is a marker of poor prognosis in a subset of patients with ovarian cancer. PMID- 7882285 TI - Second primary tumors in patients with head and neck squamous cell carcinoma. AB - BACKGROUND: The concept that a patient could develop cancer twice was first put forward by Billroth. Second primary neoplasms are a particular feature of head and neck cancer. METHODS: This study examines the records of 3436 patients with squamous cell carcinoma of the head and neck, of whom 274 subsequently developed a second neoplasm. RESULTS: The actuarial second primary rate was 9.1% at 372 months, and median time to presentation for the second tumor was 36 months. Second tumors were more likely to occur in male patients younger than 60 years at the time of their index tumor, and who had laryngeal and oral cavity index tumors. Patients whose index tumor was small at diagnosis had a greater chance of developing a second tumor as did those with no cervical lymph node metastases to the neck. Radiotherapy to the index tumor was not associated with an increased risk of developing a second tumor. The commonest sites for second tumors were the head and neck (50%) and the lung (34%), and 86% were squamous cell carcinomas. The tumor-specific mortality for those who developed a second primary tumor was 20% after 15 years compared with 44% for patients who did not develop a second primary tumor. The 5-year survival for patients who developed a secondary tumor from the time of its diagnosis was 26%. CONCLUSIONS: Second primary tumors in the head and neck of patients with cancer are not uncommon. If the second tumor occurs in the head and neck region, the prognosis is reasonably good. PMID- 7882284 TI - p53 mutations, O6-alkylguanine DNA alkyltransferase activity, and sensitivity to procarbazine in human brain tumors. AB - BACKGROUND: In human brain tumors, sensitivity to procarbazine as measured by sensitivity in a xenograft tumor model correlated inversely with amounts of the DNA repair enzyme O6-alkylguanine DNA alkyltransferase (AT). METHODS: To test the hypothesis that mutations of the p53 tumor suppressor gene in human tumors also can correlate with the response to chemotherapy, p53 mutations2 were identified in primary human malignant brain tumors and cell lines in which AT activity and procarbazine sensitivity in a xenograft model was ascertained. RESULTS: Mutations were identified in 7 of 21 (33%) specimens tested. Specimens containing p53 mutations tended to exhibit an increased growth delay in procarbazine-treated xenografts and lower amounts of AT. CONCLUSIONS: p53 mutations in brain tumors may contribute to procarbazine sensitivity by failing to induce arrest at the G1/S cell-cycle checkpoint, thereby preventing the repair of procarbazine-induced genetic alterations. PMID- 7882286 TI - A new preparatory regimen for autologous bone marrow transplantation for patients with lymphoma. AB - BACKGROUND: This trial studied the feasibility and efficacy of a new preparatory regimen for autologous bone marrow transplantation for patients with advanced lymphoid malignancies. METHODS: Twenty-one patients with Hodgkin's disease (n = 12) and non-Hodgkin's lymphoma (n = 9) were treated in this study. Lomustine was substituted for carmustine) in a dose-escalation study with an initial dose of 6 mg/kg and increasing by 3 mg/kg in groups of four patients. The preparatory regimen consisted of lomustine (6-15 mg/kg) orally on Day -6, etoposide (60 mg/kg) intravenously (i.v.) on Day -4, and cyclophosphamide (100 mg/kg) i.v. on Day -2. Peripheral blood progenitor cells and/or bone marrow were infused on Day 0. RESULTS: Lomustine was well tolerated in all patients with no significant toxicity specific to this drug. Engraftment was prompt: the time to achieving greater than or equal to 500 granulocytes/microliters was 12 days (range, 9-16 days) and the time to achieving greater than or equal to 25,000 platelets/microliters without transfusion support was 16 days (range, 9-22 days). Five patients experienced interstitial pneumonitis, three of whom had active or recent interstitial pneumonitis before bone marrow transplantation, and one who just completed mantle irradiation. Three patients died from this preparatory regimen, one of progressive interstitial pneumonitis, one of Legionella pneumonia, and one of multiorgan failure. Three patients with non-Hodgkin's lymphoma relapsed. Fourteen patients are currently alive and disease free to date. The actuarial are currently alive and disease free to date. The actuarial disease free survival was 57%, with a median follow-up of 23 months (range, 1-48 months). CONCLUSION: The preparatory regimen consisting of lomustine/etoposide/cyclophosphamide is active in treating patients with lymphomas. Further trials with high doses of lomustine are warranted. PMID- 7882287 TI - Hodgkin's disease in Mexico. Prevalence of Epstein-Barr virus sequences and correlations with histologic subtype. AB - BACKGROUND: The Epstein-Barr virus (EBV) has been linked to several human malignancies, including Hodgkin's disease (HD). In addition, epidemiologic studies have shown differences in HD occurrence in different parts of the world. The authors studied 27 cases of Hodgkin's disease from Mexico to determine the prevalence of EBV in HD in this developing nation. METHODS: The Epstein-Barr virus was investigated using in situ hybridization with the EBER1 probe. Immunohistochemical studies were performed on paraffin sections. Cases from both adult and pediatric age groups were included. Correlations with histologic subtype, clinicopathologic features, and immunophenotype were determined. RESULTS: Epstein-Barr virus sequences were identified in 18/27 (67%) cases. Positivity correlated with histologic subtype: 0/1 lymphocyte predominant; 6/13 (46%) nodular sclerosis; 7/7 mixed cellularity (MC) (100%); and 5/6 (83%) lymphocyte depleted (LD). The proportion of cases classified as MC and LD (13 of 27) was greater than that found in the United States and other developed countries. The immunophenotypic profile was appropriate for Hodgkin's disease, with all cases of classic Hodgkin's disease positive for CD30 (Ber-H2) and 18 cases expressing CD15. One case of lymphocyte-predominant Hodgkin's disease was CD20 (L26)-positive as were three cases of classic Hodgkin's disease. Patient age ranged from 5 to 65 years, with a median of 29 years. CONCLUSIONS: The EBV is associated highly with HD in Mexico, and this prevalence rate is found in all age groups. A strong correlation between EBV expression and histologic subtype was confirmed, with 92% of MC and LD subtypes found to be positive. PMID- 7882288 TI - Risk factors for infection of adult patients with cancer who have tunnelled central venous catheters. AB - BACKGROUND: Long-dwelling tunnelled central venous catheters provide reliable access for infusion therapy of patients with cancer, but can result in serious bloodstream infections. The incidence of such infections has been documented, but few studies have assessed potential risk factors, and to the authors' knowledge, none have measured the effect of neutropenia upon the incidence of these infections. METHODS: A cohort of 71 adult patients with cancer with long-dwelling tunnelled central venous catheters was followed for a total of 12,410 catheter days until catheter removal, death, or end of study for the occurrence of catheter-related infection or sepsis of unknown origin. Fifteen factors were assessed for association with these infections. RESULTS: Thirteen patients (18%) experienced a catheter-related infection (1.0/1000 catheter days), and 23 (32%) experienced sepsis of unknown origin. Neutropenia was associated significantly with risk for catheter-related infection (relative risk [RR] = 15.1, 95% confidence interval [CI] 2.7-86.9) and sepsis of unknown origin (RR = 10.3, 95% CI 4.0-26.8). Inpatient status, acute leukemia, and cytosine arabinoside therapy also were associated with sepsis of unknown origin, but not when adjusted for neutropenia. CONCLUSION: Of the 15 potential risk factors studied, neutropenia was the only independent risk factor for infection related to long-dwelling tunnelled central venous catheters and for sepsis of unknown origin. PMID- 7882289 TI - Kaposi's sarcoma of internal organs. A multiparameter study of 86 cases. AB - BACKGROUND: During the past decade, Kaposi's sarcoma (KS), one of the most common acquired immune deficiency syndrome-defining diseases, has been the subject of sustained research. However, basic questions about its etiology, histogenesis, growth, and dissemination remain unanswered. Even its nature, whether hyperplasia or neoplasia, is still controversial. Most studies and concepts to date have been based on dermatologic KS. The present study, in contrast, examines by various parameters a series of patients with KS of internal organs. MATERIALS AND METHODS: The series includes 86 cases (39 surgical specimens and 47 autopsies) of visceral and disseminated KS. The study is focused on the gross distribution of lesions, the mode of dissemination, the histologic patterns, and the cellular immunophenotypes, which are investigated with the use of 18 monoclonal antibodies. RESULTS: The involvement of various organs, multiplicity of lesions, and progression of tumors were recorded. Seven histologic patterns forming a spectrum of cellular differentiation were distinguished. Immunophenotypes characteristic for different histologic patterns were recognized. Although some cell markers such as those recognized by antibodies against Factor VIII R-Ag, Actin, and Ulex europaeus were restricted to the well differentiated KS cells, others including CD34 and CD31 demonstrated a strong affinity for the entire spectrum of KS cell differentiation. CONCLUSION: The present study of KS of internal organs revealed that poor grades of histologic and immunophenotypic differentiation correlated with invasion and dissemination, which are fundamental characteristics of malignant tumors. PMID- 7882290 TI - Joint meeting on the feasibility of a study of screening premenopausal women (40 49 years) for breast cancer: April 20-21, 1994. PMID- 7882291 TI - Enhanced expression of catalytic subunit isoform PP1 gamma 1 of protein phosphatase type 1 associated with malignancy of osteogenic tumor. AB - The expressions of the three catalytic subunits of protein phosphatase (PP) type 1 and 2A, PP1 alpha, PP1 gamma 1, and PP2AC, were examined in 14 cases of three types of osteogenic tumor using immunohistochemical analysis. The percentage of tumor cells stained positively with antiserum against PP1 catalytic subunit isoform PP1 gamma 1 was significantly higher in malignant osteogenic tumors than in benign osteogenic tumors. Furthermore, malignant osteogenic tumor showed markedly high S-phase fraction in the cell cycle of tumor cells, as compared to benign osteogenic tumors. These results suggest that PP1 gamma 1 is involved in the accelerated growth of malignant cells in osteogenic tumors. PMID- 7882292 TI - Effect of the delivery system on the biodistribution of Ge(IV) octabutoxy phthalocyanines in tumour-bearing mice. AB - The pharmacokinetic properties of the Ge(IV)-octabutoxy-phthalocyanines (GePc) with two axially ligated triethylsiloxy (GePcEt) or trihexyl-siloxy (GePcHex) chains were studied in BALB/C mice bearing a transplanted MS-2 fibrosarcoma. The GePcs were delivered to mice after incorporation into unilamellar liposomes of dipalmitoyl phosphatidylcholine (DPPC) or in an emulsion of Cremophor-EL. The Cremophor delivered GePcs were cleared from the blood circulation at a much slower rate than the liposome-delivered GePcs. At the same time, Cremophor induced a slower and reduced uptake of the GePcs in the liver and spleen while it greatly enhanced the uptake in the tumour as compared to liposomes. Maximum tumour uptake was observed at 24 h post-injection and was equivalent to 0.67 and 0.50 nmol/g, respectively, for the Cremophor delivered GePcHex and GePcEt. The corresponding values for the liposome-delivered drugs were approximately one fourth of that observed with Cremophor. PMID- 7882293 TI - A critical appraisal of intratracheal instillation of benzo[a]pyrene to Syrian golden hamsters as a model in respiratory tract carcinogenesis. AB - Several experimental models have been developed to study respiratory tract carcinogenesis. The most widely applied in vivo model uses Syrian golden hamsters which receive intratracheal instillations of a suspension of benzo[a]pyrene (B[a]P) particles attached to ferric-oxide (Fe2O3) particles in saline; it was first described by Saffiotti et al. [1]. This model has several benefits compared with other experimental models; however, the large number of variables affecting the tumour response is a clear disadvantage because the tumour response is difficult to control. In this review, we describe a systematic analysis of various variables that may influence the tumour response of the respiratory tract with the aim to further standardize the method and increase, through that, its suitability and predictability. The most important variables influencing the tumour response, as shown by statistical analysis of 29 representative studies, turned out to be the administered dose and the particle size. Both these variables influence the actual dose and the contact-time of the B[a]P particles with the target cells. The present study does not support the widespread opinion that ferric-oxide particles enhance the tumour response of the respiratory tract. In conclusion to the present analysis, some recommendations are made which probably increase the predictability of the model. PMID- 7882294 TI - Epstein-Barr virus DNA is present both in CD10/CD77 positive and negative subsets of human tonsillar lymphocytes. AB - We report the fractionation of freshly isolated subsets of tonsillar lymphocytes according to cell density and double sorting for the differential expression of CD10 and CD77, and their analysis for the presence of Epstein Barr virus genome by nested PCR. All the subsets of tonsillar lymphocytes gave unequivocal evidence for the presence of EBV DNA, when obtained from EBV seropositive individuals. Confirmation of all cases examined demonstrates that B lymphocytes from the germinal centers of tonsils are also involved in carrying the EBV infection in vivo. PMID- 7882295 TI - Messenger RNA expression of resistance factors and their correlation to the proliferative activity in childhood acute lymphoblastic leukemia. AB - In this report we analyzed the mRNA expression of the resistance-related enzymes DNA topoisomerase II (Topo II), thymidylate synthase (TS), glutathione S transferase-pi (GST-pi) and glutathione peroxidase (GP) in childhood acute lymphoblastic leukemia (ALL) and their correlation to the proliferative activity, determined by Ki-67. RNA of blast cells from 54 children with untreated ALL were examined by dot blot hybridization. We found a significant positive correlation between Topo II and TS and cell proliferation. No significant correlation was detected between the mRNA expression of the glutathione-dependent enzymes GST-pi or GP and Ki-67. The results were substantiated by a semiquantitative RT-PCR assay and by immunocytochemistry. PMID- 7882296 TI - Combination of immunotherapy with cyclophosphamide/actinomycin D chemotherapy potentiates antileukemic effect and reduces toxicity in a L1210 leukemia model in mice. AB - The therapeutic effects of the combination of chemotherapy (cyclophosphamide and actinomycin D) and immunotherapy (TNF-alpha and macrophages) were evaluated on L1210 leukemia in mice. When given as single agents, both cyclophosphamide (CY), administered intraperitoneally 2 days after subcutaneous inoculation of leukemic cells, and actinomycin D (Act D), injected intratumorally (i.t.) 4 days following injection of leukemic cells, exerted therapeutic effects and prolonged mice survival. Unexpectedly, combination of CY and Act D did not result in prolongation of mice survival, due mainly to substantial cumulative toxic effects that led to death in several cases. Immunotherapy with TNF-alpha and M phi, injected i.t. on day 4 following inoculation of leukemic cells, did not give significant therapeutic effect, either when used alone or when used in conjunction. However, combination of chemotherapy and immunotherapy, including all four agents, produced a beneficial effect resulting in significant prolongation of the survival of leukemia-bearing mice. This study indicates the potential of appropriate combinations of cytotoxic drugs with immunotherapy against neoplasia. PMID- 7882297 TI - Utility of plasmatic levels of alpha-1-antiprotease (A1AP) as a cancer marker. AB - The objective of this study was to evaluate the diagnostic utility as a cancer marker of plasmatic levels of A1AP. This case-control study included 135 cancer patients from different sites, confirmed histologically, and 95 controls (57 normal individuals plus 38 chronically ill patients with non-tumoral diseases). Determination of A1AP was done by a nephelometric procedure using a laser nephelometer as the measuring instrument. There were no sex or age related variations in plasmatic A1AP. Mean values of A1AP in 57 normal controls was 2.87 milligrams (95% C.I., 2.58-3.15); in 95 non-tumoral individuals, including 38 chronic non-malignant diseases plus 57 normal controls, 3.09 milligrams (2.46 3.72) and in malignant tumors, 4.12 milligrams (3.80-4.45). There was a statistically significant difference between chronic diseases and normal controls (P < 0.05) and also between cancer patients and non-tumoral individuals, normal control and chronic non-tumoral diseases (P < 0.001). The means of plasmatic A1AP by tumoral site are increasing in this order: breast, gastrointestinal, head and neck, and lung. The means by clinical stage are increasing in this order: complete remission, local disease, local-regional disease and metastatic disease. The calculated cutoff value, excluding complete remission cases, is 3.37 milligrams, with sensitivity 67.7% and specificity 67.7%. We conclude that there is an increase of plasmatic A1AP in cases of clinically active cancer compared with normal controls and normal range values in clinical complete remission. It can be an acceptable cancer marker that discriminates cancer from chronic non tumoral diseases and complete clinical remission from relapses. PMID- 7882298 TI - Diamine-oxidase activity and tissue di- and poly-amine contents of human ovarian, cervical and endometrial carcinoma. AB - In view of the conflicting reports regarding the association of di- and poly amines along with diamine oxidase (DAO) activity in human carcinomatous growths, the present study was undertaken to establish their interrelation and to justify whether analysis of di- and poly-amine contents along with DAO may have any diagnostic value in the assessment of the carcinomatous state. It was found that diamines like histamine, putrescine and cadaverine, and polyamines like spermine and spermidine, and also DAO, increased unequivocally in human ovarian, cervical and endometrial carcinoma in comparison with their adjoining normal tissues. A reasonable explanation has been put forward to support the observations made. PMID- 7882299 TI - Further evidence for promoter-dependent development of hepatoblastoma in the mouse. AB - In previous studies, we found that male D2B6F1 mice fed phenobarbital (PB) for 53 weeks following N-nitrosodiethylamine (NDEA) initiation developed a high (70-80%) incidence of malignant hepatoblastomas. A very low (3.3%) incidence of such tumors occurred in the absence of promoter treatment in NDEA-initiated mice observed for 60 weeks, although nearly 50% of these animals developed hepatocellular lesions. To investigate whether hepatocellular lesions in NDEA initiated mice or spontaneous hepatocellular lesions promoted by PB in mice given PB but no NDEA, progress to hepatoblastomas later in life, mice exposed to NDEA alone and PB alone were maintained for 110 weeks. Hepatocellular tumors (adenomas and carcinomas) occurred in almost all (97%) mice given NDEA alone. However, only 10% of NDEA-treated mice developed hepatoblastomas. Thus, despite its ability to induce hepatocellular neoplasms, NDEA treatment alone was rarely sufficient to induce hepatoblastomas in these mice. In contrast, PB treatment in the absence of NDEA initiation promoted the development of spontaneously occurring hepatocellular lesions, a significant number (37%) of which progressed to hepatoblastomas. Our observations clearly show that in this animal model the development of hepatoblastoma from its precursor cells (hepatocellular adenoma and carcinoma cells) occurs predominantly in the presence of promoting agents such as PB. PMID- 7882301 TI - Positive correlation of plasma transforming growth factor-beta 1 levels with tumor vascularity in hepatocellular carcinoma. AB - Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in tumor progression by promoting angiogenesis or suppressing immune system. We reported previously that transforming growth factor-beta 1 (TGF-beta 1) is overproduced by human hepatocellular carcinoma (HCC) tissues and that plasma TGF-beta 1 levels are elevated in patients with HCC. In the present study, we investigated the relationship between plasma TGF-beta 1 levels and tumor vascularity as assessed by conventional celiac angiography in 17 patients with HCC. The plasma TGF-beta 1 level did not correlate with tumor size or underlying liver disease. However, we found that plasma TGF-beta 1 levels correlated positively with the tumor vascularity. These results suggest that excessive TGF-beta 1 production may contribute to tumor angiogenesis in HCC. PMID- 7882300 TI - Variable-region sequences for T-cell receptor-gamma and -delta chains of rabbit killer cell lines against Shope carcinoma cells. AB - A rabbit gamma delta killer T-cell line against Shope carcinoma cells was established from peripheral blood lymphocytes (PBL) of a human T-lymphotropic virus type I (HTLV-I)-infected rabbit bearing Shope papilloma and carcinoma. Southern hybridization analysis of this cell line with an HTLV-I probe showed that the cell line contained multiple clones of HTLV-I-transformed cells, and three sublines with different integration patterns of the HTLV-1 genome were isolated by cloning of the cell line. In all these sublines T-cell receptor (TCR) gamma and -delta genes were rearranged and expressed. A PCR-based analysis of the expression of variable (V) genes showed that the killer cell line preferentially expressed V gamma 1.1 and V delta 1 genes, whereas V gamma 2 and V delta 1 genes were dominantly expressed in normal PBL. Analysis of the junctional sequences of TCR-gamma and -delta genes which dictate the fine specificities of epitope recognition revealed that all three sublines expressed V gamma 1.1/V delta 1 genes without the nucleotide diversity at the V-J junctions. PMID- 7882302 TI - Cytotoxic interactions of tumor necrosis factor, melphalan and 41.8 degrees C hyperthermia. AB - Experience with limb perfusion-hyperthermia, TNF, and L-PAM suggests dramatic clinical responses in sarcoma and malignant melanoma. To extrapolate these results to clinical 41.8 degrees C whole-body hyperthermia (WBH) and systemic therapy, we studied the cytotoxic interactions of TNF, L-PAM and hyperthermia in L929 cells. The optimal sequence was TNF preceding 41.8 degrees C hyperthermia by 48 h, and L-PAM given simultaneously with heat. Trimodality synergism between TNF, hyperthermia and L-PAM was demonstrated. Non-cytotoxic doses of TNF had a super-additive interaction with L-PAM/heat. Conversely, non-cytotoxic doses of L PAM had super-additive interactions with TNF followed by hyperthermia. Relative to therapeutic index, we studied WBH, L-PAM and TNF in non-tumor bearing mice. The optimal trimodality sequence did not result in increased normal tissue toxicity compared to L-PAM alone. The concentrations and sequencing of TNF and L PAM studied are consistent with clinical application to WBH. PMID- 7882303 TI - mRNA phenotyping of the major ligands and receptors of the EGF supergene family in human ovarian epithelial cells. AB - mRNA amplification phenotyping (MAPPing) was used to determine the level of mRNA expression of the major EGF-related ligands (EGF, TGF-alpha, and Amphiregulin) and receptors (EGF-receptor and erbB-2) of the EGF supergene family in three ovarian carcinoma lines (OVCA 429 and 433, and NIH:OVCAR-8) under serum supplemented and reduced serum (minimal medium with 2% fetuin) growth conditions. mRNA levels of TGF-alpha, EGF-R, and erbB-2 were particularly high, and increased approximately 2-3 orders of magnitude when grown in serum, consistent with an autocrine involvement of these genes in ovarian epithelial growth in vitro. Moreover, even when grown without serum, OVCA 429 and NIH:OVCAR-8 expressed elevated levels of mRNA for erbB-2. PMID- 7882304 TI - Tumor-conditioned medium increases macromolecular permeability of endothelial cell monolayer. AB - The permeation of macromolecular FITC-labeled dextran (molecular weight 70,000) through bovine aortic endothelial cells (BAEC) monolayer, which were cultured for 5 days with conditioned medium prepared from mouse melanoma B16, was increased. However, when BAEC, which were cultured with normal medium until confluent, were treated with B16 conditioned medium (B16-CM) for 30 min, the permeability did not increase. The B16-CM also increased the permeability of the endothelial monolayers of bovine veins and the human umbilical vein, but did not increase that of the epithelial monolayer. The B16-CM did not alter the distribution or content of F-actin on the BAEC. BAEC cultured in the presence of B16-CM for 5 days were detached from the dish, and then seeded into a chamber at one-fifth of confluent cell density. After 5 days of culture in normal medium, the BAEC were grown to confluence and their permeability was increased. These findings suggest that B16-CM increased the endothelial permeability irreversibly without the decrease of F-actin, and that soluble factor(s) which were secreted from the tumor cells participate in the construction of the hyperpermeable structure of tumor vessels in vivo. PMID- 7882305 TI - Differentially expressed genes in TGF-beta 1 sensitive and resistant human hepatoma cells. AB - The pathway of growth inhibitory cellular signal transduction by transforming growth factor beta 1 is largely unknown. Although several cellular proteins have been shown to be involved in the pathway, others remain to be identified. To search for other involved proteins, differentially expressed genes were examined in two human hepatoma cell lines that were respectively sensitive and resistant to growth inhibition by TGF-beta 1. Two such genes (SB31 and SB16) were characterized and found to be 100% homologous to leucine-rich alpha 2 glycoprotein and the ribosomal protein S25, respectively. SB31 was coordinately expressed with the TGF-beta I type II receptor, implicating a possible interaction. Expression of both genes in different cell lines can be broadly correlated with the sensitivity of the cell lines to growth inhibition by TGF beta 1. SB16 expression is strongly suppressed in rat liver regeneration after partial hepatectomy, suggesting that it may have a role in liver growth. PMID- 7882306 TI - Effects of partial hepatectomy on initiation of liver cell foci by 4 nitroquinoline 1-oxide, a non-hepatocarcinogen, and generation of DNA adducts in rats. AB - The influence of administration time after partial hepatectomy (PH) on liver cell foci induction and generation of DNA adducts by tritiated or non-tritiated 4 nitroquinoline 1-oxide (4NQO), a reported non-hepatocarcinogen, was investigated. With the use of the resistant hepatocyte model (Experiment I), 4NQO (20 mg/kg body wt. i.g.) was administered to 7-week-old male F344 rats at various times from 6 h before to 24 h after PH. Numbers and areas of glutathione S-transferase placental from (GST-P) positive liver cell foci gradually increased as the interval between PH and administration of 4NQO was prolonged to 24 h. In a 4NQO DNA adduct study (Experiment II-a), adduct levels in the liver, pancreas and lung of partially hepatectomized rats were found to be appreciable 6-20 h after administration of 4NQO. In the adduct study (liver, pancreas and lung) after PH (Experiment II-b), 4NQO administration from the 0- to 18-h time points was associated with significantly marked elevation (P < 0.001-0.01) of adduct levels as compared to the carcinogen control value, while by 24 h the formation of adducts had again decreased significantly. The findings suggest that cell proliferation with effective DNA adduct levels is important for initiation of foci development. PMID- 7882307 TI - Mutagenicity of furfural in plasmid DNA. AB - Furfural is recognized as a dietary mutagen and is present in various foods and beverages. We have examined the mutagenic effect of furfural induced lesions in plasmid pBluescript SK(+/-). There was a progressive decrease in the transformation capacity of the plasmid as a function of furfural concentration with a concomitant increase in the number of mutant plasmids. Several mutant plasmids with reduced transformation capacity and a molecular size similar to the parental plasmid were isolated. A stretch of DNA of 108 basepairs within the multiple cloning region was sequenced. It was observed that the number of mutagenic events in the case of furfural damaged plasmid was not significantly greater than in spontaneously arisen mutants. These results were interpreted to indicate that furfural mediated DNA damage is efficiently repaired. PMID- 7882308 TI - Chromosomal mapping of members of the cdc2 family of protein kinases, cdk3, cdk6, PISSLRE, and PITALRE, and a cdk inhibitor, p27Kip1, to regions involved in human cancer. AB - Orderly progression through the cell cycle requires sequential activation and inactivation of cyclin-dependent kinases (cdks). This is achieved in part through the association of cdks with positive regulators called cyclins and inactivation of cyclin-cdk complexes by a rapidly growing number of cyclin-cdk inhibitors. Recently, the role of cell cycle control proteins both as primary effectors and as mediators of tumorigenesis has become a subject of increased interest. Here we report the chromosomal mapping of two cdks, cdk3 and cdk6, two putative cdks, PISSLRE and PITALRE, and one cyclin-dependent kinase inhibitor, p27, to chromosomal regions which may be altered in human tumors and examine their possible involvement in some of these malignancies. In particular, two of the kinases, cdk3 and PISSLRE and PITALRE, the cdc2-related kinases recently cloned by us, map to regions previously shown to exhibit loss of heterozygosity in breast and other tumors. PMID- 7882310 TI - p27Kip1: chromosomal mapping to 12p12-12p13.1 and absence of mutations in human tumors. AB - The p27Kip1 gene codes for a cyclin-dependent kinase inhibitor implicated in G1 arrest by transforming growth factor beta, cell-cell contact, agents that elevate cyclic AMP, and the growth-inhibitory drug rapamycin. p27 binds to and inhibits complexes formed by cyclin E-cdk2, cyclin A-cdk2, and cyclin D-cdk4. The involvement of p27 in the negative regulation of cell proliferation suggests that it may also function as a tumor suppressor gene. Using a combination of somatic cell hybrid panels and fluorescence in situ hybridization p27Kip1 has been mapped to the short arm of chromosome 12 at the 12p12-12p13.1 boundary, reported to harbor deletions and rearrangements in leukemia and mesotheliomas. In order to assess potential p27Kip1 gene alterations, we have screened a total of 147 human primary solid tumors and found no detectable cancer-specific mutations. These results argue that the often observed loss of antimitogenic transforming growth factor beta responsiveness in human cancer cells is not due to structural defects in p27Kip1. PMID- 7882309 TI - Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias. AB - The p27Kip1 (p27) gene encodes an inducible inhibitor of cyclin-dependent kinase activity. Using a murine p27 cDNA as probe, we obtained a human cDNA clone and subsequently used it to isolate a genomic clone of this gene. The coding region of the human p27 gene was contained in two exons. Both the amino acid sequence and intron-exon organization of p27 were similar to those previously found for the related cyclin-dependent kinase inhibitor p21Waf1 (p21). The p27 gene was localized to chromosome band 12p13 by a combination of somatic cell hybrid and fluorescence in situ hybridization analyses. The p27 gene product is thought to control the leukocyte cell cycle and the 12p13 chromosomal band is known to be deleted in leukemias, suggesting that the p27 gene may act as a tumor suppressor gene in leukemias. Although p27 was found to reside in the minimal region of chromosomal loss in hematological malignancies, no mutations of p27 were observed in leukemia samples. Haploinsufficiency of p27 may confer a growth advantage to leukemia cells. PMID- 7882311 TI - Suppression of the formation of sister chromatid exchanges by low concentrations of ginsenoside Rh2 in human blood lymphocytes. AB - To assess the antimutagenic potentials of ginsenoside Rh2 (Rh2), its effects on the baseline and mitomycin C-induced sister chromatid exchange (SCE) were examined in human peripheral blood lymphocytes (PBLs). The SCE frequency in PBLs treated with various concentrations of Rh2 for 72 h was decreased in a dose dependent manner and was significantly lower than the baseline levels at 1.0 x 10(-10) M and 1.0 x 10(-7) M. The SCE frequency in PBLs treated with both Rh2 and mitomycin C was significantly (P < 0.001) less than that in PBLs treated with only mitomycin C. Cell cycle kinetics, as indicated by the proliferation and mitotic indices, was not significantly affected by Rh2 of various concentrations in the PBLs throughout the present experiments. This is the first report which showed convincingly a reduction of SCE in normal human cells. The mechanism remains to be elucidated in future studies. PMID- 7882312 TI - Glutathione transferase (GSTM1) null genotype, smoking, and prevalence of colorectal adenomas. AB - Colorectal cancer is caused by environmental exposures and genetic predisposition. However, little is known of hereditary factors that influence development of common, non-Mendelian forms of this cancer. Interactions among carcinogen exposure, hereditary variants of enzymes involved in carcinogen metabolism, and other host factors may play a role. Genetic polymorphisms of carcinogen metabolism, such as the glutathione transferase M1 (GSTM1) null genotype, are thus possibly related to cancer risk. The GSTM1 enzyme detoxifies mutagens formed from polycyclic aromatic hydrocarbons which are found in tobacco smoke. We analyzed GSTM1 genotypes and smoking among 488 controls and 446 individuals with a first time diagnosis of colorectal adenomas which are precursors to cancer. Subjects were from two Kaiser Permanente sigmoidoscopy clinics in southern California. We observed no overall effect of the GSTM1 null genotype on the risk for colorectal adenomas (odds ratio, 0.85; 95% confidence interval = 0.65-1.10). The odds ratio for smokers with the null genotype was 2.07 (95% confidence interval = 1.14-3.77) when compared to "never smokers" without the null genotype. Using this same reference group, the odds ratio for smokers without the null genotype was 1.73 (95% confidence interval = 1.03-2.90). These two odds ratios were not significantly different (P = 0.30). PMID- 7882313 TI - Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. AB - We have found 16 of 28 small cell lung cancers, 17 of 31 non-small cell lung cancers, 2 of 3 carcinoids, and 12 of 14 mesotheliomas that had chromosome 22 cytogenetic abnormalities. To determine whether the neurofibromatosis type 2 (NF2) gene located on chromosome 22 participates in the oncogenesis of these malignancies, we studied DNAs from lung cancer cell lines and mesotheliomas using Southern blot analysis and the single-strand conformation polymorphism (SSCP) technique for mutations covering 8 of the 16 known NF2 exons. We detected 7 mutations in 17 mesotheliomas (41%) within the coding region of NF2 but none in 75 lung cancer cell lines (38 small cell lung cancers, 34 non-small cell lung cancers, and 3 carcinoids). These mutations were found to be somatic when normal tissue was available for testing. Four mesothelioma cell lines had relatively large deletions (approximately 10-50 kilobases) in the NF2 gene detectable by Southern blot analysis. Two mesothelioma cell lines had nonsense mutations at codons 57 and 341, respectively. Another mesothelioma obtained as a specimen directly from a patient, had a 10-base pair microdeletion from nucleotide 1004 to nucleotide 1013 causing a frameshift mutation. These results suggest that the NF2 gene participates in the oncogenesis in a subset of mesotheliomas but not in lung cancers. PMID- 7882314 TI - Defective repair of DNA double-strand breaks and chromosome damage in fibroblasts from a radiosensitive leukemia patient. AB - A radiation-sensitive fibroblast culture (180BR) established from an acute lymphoblastic leukemia patient who died following radiotherapy is defective in the repair of radiation-induced DNA double-strand breaks. The cells also show a reduced capacity to repair interphase chromosome damage visualized by means of premature chromosome condensation and metaphase chromosome aberrations measured by fluorescence in situ hybridization on chromosome 4. This case represents the first example in humans where hypersensitivity to ionizing radiation can be ascribed directly to a defect in DNA and chromosome repair, and the defect may underlie the cancerous phenotype observed. PMID- 7882315 TI - DNA strand break rejoining defect in xrs-6 is complemented by transfection with the human Ku80 gene. AB - The radiosensitive mutant xrs-6, derived from Chinese hamster ovary cell line CHO K1, has been demonstrated to be defective in DNA double-strand break repair and also in its proficiency to undergo V(D)J recombination. Recent work has provided both genetic and biochemical evidence that the M(r) 80,000 subunit of the Ku protein is able to complement the radiosensitivity and the V(D)J recombination defect in the xrs-6 mutant. We demonstrate here that complementation of the radiosensitive phenotype in xrs-6 cells by the introduction of Ku80 cDNA is accompanied by the concomitant restoration of DNA double-strand break rejoining proficiency to almost that of the parental CHO-K1 cells, as measured both by neutral single-cell microgel electrophoresis (Comet) technique and by pulsed field gel electrophoresis. These results provide further biochemical evidence for the involvement of the Ku protein in the repair of DNA double-strand breaks. PMID- 7882316 TI - Attenuation of the antitumor activity of 5-fluorouracil by (R)-5-fluoro-5,6 dihydrouracil. AB - 5-Ethynyluracil (5-EU; 776C85) is a potent mechanism-based inactivator of dihydropyrimidine dehydrogenase that improves the antitumor activity of 5 fluorouracil (5-FU) to a greater extent than can be accounted for by the improved 5-FU pharmacokinetics that result from preventing the catabolism of 5-FU. We therefore tested the effects of (R)-5-fluoro-5,6-dihydrouracil (5-FUH2), the 5-FU catabolite extensively formed in the absence of 5-EU, on the antitumor activity and toxicity of 5-FU in 5-EU-treated rats bearing large s.c. tumors. Rats were dosed once weekly for 3 weeks with the following regimens: 100 mg/kg 5-FU (maximum tolerated dose), 10 mg/kg 5-FU 1 h after 1 mg/kg 5-EU, or 10 mg/kg 5-FU plus 90 mg/kg 5-FUH2 1 h after 1 mg/kg 5-EU. The latter regimen was designed to approximate the exposure produced from 5-FU in the absence of 5-EU, where > 80% of the dose is catabolized. 5-FU produced complete and sustained tumor regressions in 94% of the animals pretreated with 5-EU. In contrast, 5-FU in combination with 5-FUH2 produced complete regression in only 38% of the 5-EU treated rats, which was similar to the antitumor activity of 5-FU in the absence of 5-EU. All treatments resulted in 7-11% transient weight loss. 5-FU produced no other notable toxicity in 5-EU-treated rats. However, 5-FUH2 added to this regimen caused transient diarrhea and stomatitis in 13% of the animals, which was similar to the toxicity produced by 5-FU in the absence of 5-EU. Thus, 5-FUH2, or other downstream catabolites of 5-FU, impaired the antitumor activity and slightly increased the toxicity of 5-FU. Accordingly, 5-EU approved to improve the efficacy of 5-FU by preventing the formation of 5-FU catabolites. PMID- 7882317 TI - In vitro and in vivo 31P nuclear magnetic resonance measurements of metabolic changes post radiation. AB - Radiation-induced metabolic changes previously observed in tumors using phosphorus nuclear magnetic resonance spectroscopy include changes in the relative amounts of the phospholipid precursors phosphoethanolamine and phosphocholine, increases in membrane catabolites, and increases in energy status. To elucidate the degree to which these in vivo alterations are a result of intrinsic cellular changes versus radiation-induced systemic effects, the Radiation-Induced Fibrosarcoma-1 tumor model was studied before and over the course of 7 days after a single dose of 17 Gy. In vivo studies were performed with tumors implanted in C3H/He mice; in vitro studies used cells that were perfused in agarose gel threads after being grown, radiated, and maintained in monolayer. The statistically significant increases in the downfield component of the phosphomonoester peak, which consists primarily of phosphoethanolamine, compared to the upfield component, phosphocholine, were qualitatively similar in vivo and in vitro post radiation. Statistically significant increases in the membrane catabolite glycerophosphocholine, a phosphodiester, were also observed in both tumors and cell culture after irradiation, with a greater percentage change in vitro. This suggests that changes in the phosphomonoester and phosphodiester concentrations are primarily an intrinsic effect of radiation on cellular metabolism, modulated to a lesser degree by systemic effects. In contrast, the statistically significant increases in energy status after the 17 Gy dose showed markedly different temporal responses in the two systems. Therefore, energy status changes observed in vivo are due largely to systemic changes, such as changes in blood flow. Flow cytometry data obtained from the cultured cells showed a sustained increase in the G2-M fraction starting at 24 h, the first time point measured after irradiation, which continued for the 7 days studied post radiation. These data indicate that the in vivo changes detected by nuclear magnetic resonance in phospholipid precursors and catabolites occur directly at the cellular level and may reflect cell death or growth inhibition after antineoplastic therapy. PMID- 7882318 TI - Changes in topoisomerase I levels and localization during myeloid maturation in vitro and in vivo. AB - Changes in topoisomerase I (topo I) levels and localization were examined during the course of granulocytic maturation in vitro and in vivo. Western blotting revealed that granulocytic maturation in DMSO-treated HL-60 human leukemia cells was accompanied by a 5-fold decrease in topo I polypeptide content. Consistent with this result, 3- to 5-fold higher concentrations of the topo I poison camptothecin were required to stabilize topo I-DNA adducts in DMSO-treated HL-60 cells compared to untreated cells. Northern blotting revealed that these changes occurred without any decrease in topo I message. Immunolocalization studies revealed that these quantitative changes were accompanied by redistribution of topo I away from the nucleoli, where it was prominently accumulated in untreated HL-60 cells, to a more uniform nuclear distribution in DMSO-treated cells. Similar changes occurred during granulocytic maturation in human marrow in vivo. Western blotting revealed that topo I levels in normal progranulocytes were 50% as high as those in HL-60 cells, levels in metamyelocytes were 35% as high as HL 60 cells, and levels in peripheral blood granulocytes were 5% as high as HL-60 cells. Two other polypeptides that are concentrated in nucleoli, poly(ADP-ribose) polymerase and B23/nucleophosmin, also decreased during the course of granulocytic maturation. These changes were accompanied by an alteration in topo I localization similar to that observed in HL-60 cells during the course of granulocytic maturation. Conversely, treatment of human lymphocytes with the mitogenic lectin concanavalin A resulted in a 3-fold increase in topo I polypeptide content concomitant with a prominent increase in the amount of nucleolar antigen. These observations not only provide a context for understanding the recent observation that topo I levels are higher in human leukemia specimens than in normal marrow but also raise the possibility that elevated topo I levels in other cells might reflect alterations in nucleolar structure and function. PMID- 7882319 TI - Malignant and nonmalignant brain tissues differ in their messenger RNA expression patterns for ERCC1 and ERCC2. AB - Perturbation of the DNA repair process appears to be responsible for the occurrence of a number of human diseases, which are usually associated with a propensity to develop internal malignancies and/or disorders of the central nervous system. We have been interested in the possibility that a subtle abnormality in DNA repair competency might be associated with the transformation of nonmalignant cells to the malignant state. To study this question, we assayed malignant and nonmalignant brain tissues from 19 individuals for mRNA expression levels of the human DNA repair genes ERCC1, ERCC2, and XPAC and for differential splicing of the ERCC1 transcript. We separately compared expression levels of these genes in the following situations: concordance of expression within malignant tissues; concordance of expression within nonmalignant tissues; concordance between malignant and nonmalignant tissues within individuals of the cohort; and concordance of gene expression between two nonmalignant tissue sites within a single individual. Linear regression analyses of mRNA values obtained suggested orderly concordance of these three DNA repair genes in nonmalignant tissues within the patient cohort and an excellent concordance of these genes between two separate biopsy sites from the same individual. In contrast, malignant tissues showed disruption of concordance between the full-length ERCC1 transcript and ERCC2, which have excision and helicase functions, respectively. Furthermore, within the same individuals, malignant tissues were discordant with nonmalignant tissues for ERCC1 and ERCC2, although concordance for XPAC was preserved. These data suggest that one molecular characteristic of human malignancy may be the disruption of the normal relationship between the excision and the helicase functions of the nucleotide excision repair pathway. PMID- 7882320 TI - Development of a human biomonitoring assay using buccal mucosa: comparison of smoking-related DNA adducts in mucosa versus biopsies. AB - The aim of this study was to determine whether buccal mucosa would provide an alternate source of tissue for human biomonitoring. Samples of clinically normal oral biopsies were excised, and buccal mucosa were scraped or brushed from patients while they were undergoing surgery for the excision of intra-oral squamous cell carcinoma. Extracted DNA was 32P-postlabeled using the butanol enhancement method, and DNA adduct levels were quantified to compare the accuracy of adduct detection in buccal mucosa versus oral biopsies. For both tissues, tobacco smokers were found to have statistically significant higher levels of DNA damage than samples obtained from nonsmokers (P < 0.001). Mean relative adduct labeling in smokers was very similar for oral biopsies (6.16 x 10(-7)) and buccal mucosa (6.73 x 10(-7)). Likewise, mean relative adduct labeling values for nonsmokers were comparable in the two tissues (1.66 x 10(-7) for biopsies and 2.1 x 10(-7) for mucosa). Overall, an excellent correlation (r = 0.79; n = 32) was obtained between adduct levels in biopsies and mucosa for all classes of patient. These data indicate that buccal mucosa provides an additional tissue for monitoring human exposure to environmental genotoxins. The tissue is obtained rapidly in a noninvasive fashion when harvested by brushing. It can clearly be used to study components in cigarette smoke which cause DNA damage, and it is on the major route of exposure to many environmental genotoxins. PMID- 7882321 TI - Cancer induction by an organic arsenic compound, dimethylarsinic acid (cacodylic acid), in F344/DuCrj rats after pretreatment with five carcinogens. AB - Arsenic (As) is environmentally ubiquitous and an epidemiologically significant chemical related to certain human cancers. Dimethylarsinic acid (cacodylic acid; DMA) is one of the major methylated metabolites of ingested arsenicals in most mammals. To evaluate the effects of DMA on chemical carcinogenesis, we conducted a multiorgan bioassay in rats given various doses of DMA. One-hundred twenty-four male F344/DuCrj rats were divided randomly into 7 groups (20 rats each for groups 1-5; 12 rats each for groups 6 and 7). To initiate multiple organs and tissues, animals in groups 1-5 were treated sequentially with diethylnitrosamine (100 mg/kg body weight, i.p., single dose at the commencement) and N-methyl-N nitrosourea (20 mg/kg body weight, i.p., 4 times, on days 5, 8, 11, and 14). Thereafter, rats received 1,2-dimethylhydrazine (40 mg/kg body weight, s.c., 4 times, on days 18, 22, 26, and 30). During the same period, the animals were sequentially administered N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05% in the drinking water, during weeks 1 and 2) and N-bis(2-hydroxypropyl)nitrosamine (0.1% in the drinking water, during weeks 3 and 4; DMBDD treatment). After a 2-week interval, groups 2-5 were given 50, 100, 200, or 400 ppm DMA, respectively, in the drinking water. Groups 6 and 7, which were not given DMBDD treatment, received 100 and 400 ppm DMA during weeks 6-30. All rats were killed at the end of week 30. In the initiated groups (groups 1-5), DMA significantly enhanced the tumor induction in the urinary bladder, kidney, liver, and thyroid gland, with respective incidences in group 5 (400 ppm DMA) being 80, 65, 65, and 45%. Induction of preneoplastic lesions (glutathione S-transferase placental form positive foci in the liver and atypical tubules in the kidney) was also significantly increased in DMA-treated groups. Ornithine decarboxylase activity in the kidneys of rats treated with 100 ppm DMA was significantly increased compared with control values (P < 0.001). In conclusion, DMA is acting as a promoter of urinary bladder, kidney, liver, and thyroid gland carcinogenesis in rats, and we speculate that this may be related to cancer induction by As in humans. PMID- 7882322 TI - Modifying effects of naturally occurring products on the development of colonic aberrant crypt foci induced by azoxymethane in F344 rats. AB - Modifying effects of dietary exposure of seven naturally occurring products on the development of colonic aberrant crypt foci (ACF) induced by azoxymethane (AOM) were investigated in male F344 rats. The effects of these compounds on proliferation biomarkers such as the number of silver-stained nucleolar organizer region protein, ornithine decarboxylase activity, and polyamine concentration in the colon were also estimated. The naturally occurring products tested included four terpenoids (rebaudioside A, oleanolic acid, costunolide, and soyasaponin A2), one flavonoid (liquiritin), and two isocoumarins (phyllodulcin and hydrangenol). Animals were given 3 weekly s.c. injections of AOM (15 mg/kg body weight) to induce ACF. These rats were fed the diet containing 200 ppm of each test chemical for 5 weeks, starting 1 week before the first dosing of AOM. All rats were sacrificed 2 weeks after the last AOM injection to estimate their modulatory effects on the occurrence of ACF and the cell proliferation biomarkers in the colon. In groups of rats given AOM and hydrangenol, oleanolic acid, or costunolide, the frequencies of ACF/colon were significantly lower than that of AOM alone (P < 0.05, P < 0.005, and P < 0.05, respectively). In groups of rats given AOM and costunolide and those treated with AOM and soyasaponin A2, both ornithine decarboxylase activity and polyamine concentration of the colonic mucosal tissue were significantly decreased compared with those in rats given AOM alone (P < 0.05 and P < 0.001 for costunolide and P < 0.001 and P < 0.05 for soyasaponin A2, respectively). In groups of rats given AOM and liquiritin, oleanolic acid, or costunolide, the numbers of silver-stained nucleolar organizer regions/nucleus were significantly lower than that of AOM alone (P < 0.05, P < 0.01, and P < 0.05, respectively). Costunolide decreased four AOM-induced biomarkers, such as the frequencies of ACF/colon, ornithine decarboxylase activity, polyamine concentration level, and silver-stained nucleolar organizer region number in the colon. These results indicate that, among the test chemicals, costunolide has blocking effects against rat colon carcinogenesis and is a possible chemopreventive agent against colon tumorigenesis. Also, the short term model described here could be a very useful prescreening tool for chemopreventive agents against colon cancer. PMID- 7882323 TI - Mutagenesis by 8-methoxypsoralen and 5-methylangelicin photoadducts in mouse fibroblasts: mutations at cross-linkable sites induced by offoadducts as well as cross-links. AB - Psoralens are used clinically in the treatment of several skin diseases, including psoriasis, vitiligo, and cutaneous T cell lymphoma. However, psoralen treatment has been associated with an increased risk of squamous cell carcinoma of the skin. To elucidate molecular events that may play a role in the psoralen related carcinogenesis, we examined psoralen-induced mutagenesis in a mouse fibroblast cell line carrying a recoverable, chromosomally integrated lambda phage shuttle vector. Using the supF gene as a mutation reporter gene, we determined the spectrum of mutations induced by photoactivation of 8 methoxypsoralen and of 5-methylangelicin. Both psoralens generated predominately T:A to A:T and some T:A to G:C transversions. Most of the mutations occurred at either 5' TpA or 5' ApT sites, both of which are conducive to interstrand cross link formation. However, 5-methylangelicin produces only monoadducts, whereas 8 methoxypsoralen generated 20% cross-links and 80% monoadducts under the conditions of our experiments, as measured by direct HPLC analysis of the DNA from the treated cells. Although most of the mutations occurred at potentially cross-linkable sites, these results implicate monoadducts, as well as cross links, as critical premutagenic lesions in psoralen-treated mammalian cells. These findings may help in the identification of carcinogenic changes induced by psoralen, and they may aid in the improved design of psoralen-based treatment regimens in the future. PMID- 7882324 TI - Mammary and submandibular gland epidermal growth factor expression is reduced by calorie restriction. AB - Calorie restriction reduces mammary mitogenesis and tumorigenesis. To test whether epidermal growth factor (EGF) levels are influenced by calorie intake, 72 four-week-old C3H/HeOu mice were separated into two groups and either fed ad libitum (group AL) or calorie-restricted at a mean 19% (group CR). Three mice from each group were evaluated when 6, 8, 10, and 12 weeks old for submandibular gland transcription of EGF and beta-actin RNA for levels of EGF protein in the submandibular gland, mammary gland, and serum and for immunohistological evidence of EGF protein within the submandibular and mammary glands. Submandibular levels of EGF RNA and protein and mammary and serum levels of EGF protein were similar between dietary groups when mice were 6 and 8 weeks old. Mean EGF:beta-actin RNA transcription in submandibular glands of 12-week-old mice were approximately 10 fold greater in AL compared to CR mice (ratio means, 1.499 versus 0.157, respectively; P < 0.01). Mean submandibular levels of EGF protein were greater in 10-week-old AL compared to CR mice (7017.4 versus 4098.5 ng/mg protein, respectively; P < 0.05) and even greater in 12-week-old AL compared to CR mice (4342.6 versus 137.9 ng/mg protein; P < 0.001). Mean mammary levels of EGF protein were greater among 12-week-old AL compared to CR mice (7.8 versus 5.0 ng/mg protein; P < 0.05). Serum levels of EGF did not differ between dietary cohorts. More anti-EGF immunoprecipitate was present in submandibular and mammary gland sections of 10- and 12-week-old AL compared to CR mice. Lowered EGF levels may contribute to the antiproliferative and antineoplastic effects of calorie restriction. PMID- 7882325 TI - Incidence of internal cancers and ingested inorganic arsenic: a seven-year follow up study in Taiwan. AB - In order to elucidate the dose-response relationship between ingested inorganic arsenic and internal cancers, a total of 263 patients with blackfoot disease and 2293 healthy residents in the endemic area of arseniasis were recruited and followed up for 7 years. The information on consumption of high-arsenic artesian well water, sociodemographic characteristics, life-style and dietary habits, and personal and family history of cancers was obtained through standardized interviews. The occurrence of internal cancers among study subjects was determined through annual health examinations, home visit personal interviews, household registration data checks, and national death certification and cancer registry profile linkages. A dose-response relationship was observed between the long-term arsenic exposure from drinking artesian well water and the incidence of lung cancer, bladder cancer, and cancers of all sites combined after adjustment for age, sex, and cigarette smoking through Cox's proportional hazards regression analysis. Blackfoot disease patients had a significantly increased cancer incidence after adjustment for cumulative arsenic exposure. PMID- 7882326 TI - Vegetable consumption, serum retinol level, and risk of hepatocellular carcinoma. AB - A cohort of 8436 men in Taiwan was recruited with personal interview and blood sample collection between 1984 and 1986. During the 5-year follow-up period, 50 incident cases of hepatocellular carcinoma (HCC) were identified. Retinol levels were measured for 35 HCC patients whose serum samples were available and 140 matched controls randomly selected from cohort members without HCC. Lower vegetable intake was significantly associated with an increased risk of HCC after adjustment for other HCC risk factors (P = 0.006). The effect of low vegetable intake on HCC risk was limited to hepatitis B virus chronic carriers and cigarette smokers. As compared with subjects who had a weekly vegetable consumption frequency of six or more meals, the multivariate-adjusted relative risk of HCC for subjects who had a frequency of less than six meals was 4.7 (95% confidence interval, 2.0-11.1; P = 0.0004) among chronic hepatitis B virus carriers and 3.8 (95% confidence interval, 1.7-8.5; P = 0.001) among cigarette smokers. There was an inverse dose-response relationship between the prediagnostic serum retinol level and the development of HCC (trend test, P = 0.003). The odds ratio of HCC for men with a retinol level in the lowest tertile was 9.0 (95% confidence interval, 2.1-39.1) compared with those with a level in the highest tertile. The relation remained after multivariate adjustment for cigarette smoking, habitual alcohol drinking, and either the seropositivity of hepatitis B virus surface antigen and/or anti-hepatitis C virus antibody or the past history of liver diseases through conditional logistic regression analysis. The association was more striking for men 55 years or younger and for those who smoked 10 or more cigarettes/day. There was a significant synergistic effect of hepatitis B virus surface antigen carrier status and low serum retinol level on the development of HCC. These data suggest a potential role of retinol in the chemoprevention of HCC. PMID- 7882327 TI - In situ cyclopentenyl cytosine infusion for the treatment of experimental brain tumors. AB - Cyclopentenylcytosine (CPEC; NSC 375575) is a pyrimidine nucleoside analogue that has potent antitumor effects when tested in vitro and also when tested in experimental tumors outside the central nervous system. CPEC exerts its antiproliferative effect through inhibition of CTP synthetase and consequent depletion of CTP and dCTP pools required for cell replication. Due to its poor penetration of the bloodbrain barrier, CPEC has failed to demonstrate therapeutic efficacy in experimental brain tumors after systemic administration. We therefore examined the in vivo activation, distribution, and antitumor effect of CPEC after long-term regional infusion of the drug directly into experimental brain tumors in rats. HPLC analysis of CPEC incubated with homogenized human brain and brain tumor tissue showed minimal degradation of the drug over 24 h. Analysis of rat cerebral 9L gliosarcoma infused with tritium-labeled CPEC demonstrated intratumoral accumulation of the active metabolite CPEC-triphosphate and concomitant depletion of CTP to a much greater extent in tumor tissue than in the adjacent brain. Tumor tissue UTP also decreased, but no significant effects on other ribonucleoside triphosphates were detected. Only trace amounts (< 1%) of CPEC and its metabolites reached peripheral sites, including the liver and kidneys, after intratumoral infusion. Rats treated with continuous intratumoral infusion of CPEC for 4 weeks using s.c. implanted osmotic pumps survived significantly longer than control rats receiving intratumoral saline or i.p. CPEC (P < 0.0001). Long-term intratumoral infusion of CPEC was not associated with any detectable toxicity. Our results support the feasibility of using intratumoral administration of CPEC as a regional therapy for malignant brain tumors. PMID- 7882328 TI - Novel antitumor indolocarbazole compound 6-N-formylamino-12,13-dihydro-1,11- dihydroxy-13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]pyrrolo[3,4- c]carbazole 5,7(6H)-dione (NB-506): induction of topoisomerase I-mediated DNA cleavage and mechanisms of cell line-selective cytotoxicity. AB - A new indolocarbazole antitumor agent, NB-506 [6-N-formylamino-12,13-dihydro-1,11 dihydroxy-13-(beta-D-glucopyranosyl) -5H- indolo[2,3-a]pyrrolo[3,4-c]carbazole 5,7(6H)-dione], enhanced the DNA cleavage catalyzed by HeLa S3 topoisomerase I at 0.01 microM but not the cleavage by topoisomerase II at 300 microM. It also caused single-strand DNA breakage in intact cells at 0.08 microM and more. Unlike the known topoisomerase I inhibitor camptothecin, NB-506 intercalated with DNA. However, the binding affinity to DNA and the inhibition against DNA polymerase alpha and RNA polymerase II were marginal compared with those of Adriamycin or actinomycin D. NB-506 inhibited the growth of various tumor cell lines at two micromoles or less, and its cytotoxicity was found to be cell line selective. This selective cytotoxicity of NB-506 was not fully explained by the differences in topoisomerase I activity in these cell lines, but there was some relationship between the amount of NB-506 accumulated in these cell lines and its cytotoxicity toward them. In conclusion, NB-506 is a potent topoisomerase I poison, acting selectively on tumor cell lines accumulating NB-506. PMID- 7882329 TI - Novel indolocarbazole compound 6-N-formylamino-12,13-dihydro-1,11-dihydroxy- 13 (beta-D-glucopyranosyl)-5H-indolo[2,3-a]pyrrolo-[3,4-c]carbazole- 5,7(6H)-dione (NB-506): its potent antitumor activities in mice. AB - NB-506 [6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(beta-D- glucopyranosyl) 5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-di one d is a new antitumor indolocarbazole compound. The growths of murine M5076 and Ehrlich solid tumors were inhibited 76 and 96%, respectively, by i.v. injection at doses of 300 mg/m2. Furthermore, NB-506 caused regression of nodules of human PC-13 lung cancer and MKN-45 stomach cancer cells at i.v. doses of 90 mg/m2. Human HCT 116 and LS 180 colon cancers also regressed with injections of NB-506. Repeated injections of NB 506 had a stronger antitumor effect than intermittent injections in mice with MKN 45. The cumulative toxicity of NB-506 was low in terms of lethality in mice, i.e., the LD50s on single and 10 repeated i.v. injections into CDF1 mice were 990 and 810 mg/m2/injection, respectively. In conclusion, NB-506 is considered to be an interesting possible candidate as an anticancer drug for treatment of solid tumors in humans. PMID- 7882330 TI - In vitro and in vivo cytotoxicity of an anti-osteosarcoma immunotoxin containing pokeweed antiviral protein. AB - Successful treatment of many patients with osteosarcoma requires more effective chemotherapy. Since new agents are needed, we have developed an immunotoxin using TP-3, an IgG2b mAb which recognizes human and canine osteosarcomas and budding capillaries of tumors. The plant hemitoxin, pokeweed antiviral protein (PAP), was conjugated to TP-3 to produce an immunotoxin highly active against osteosarcoma. After 48 h no viable human OHS osteosarcoma cells were present in cultures containing TP-3-PAP as demonstrated by the absence of [3H]thymidine uptake into DNA. Furthermore, clonogenic assays indicated > 3.9 log kill of OHS at 18 h. The IC50 of TP-3-PAP against OHS was 3.5 +/- 1.0 (SD) x 10(-12) M. TP-3 mAb without PAP had no effect on OHS proliferation; PAP alone had no effect on OHS growth unless concentrations > 1000 pM were used. When TP-3-PAP (1.25 micrograms-10.0 micrograms) was given i.p. q.d. on days 3-5 after tumor inoculation, a dose dependent reduction of the number of lung metastases was observed (P < 0.001). These results indicate that the TP-3-PAP immunotoxin may be useful in the treatment of osteosarcoma and some soft tissue sarcomas. PMID- 7882331 TI - Overexpression of ribonucleotide reductase in transfected human KB cells increases their resistance to hydroxyurea: M2 but not M1 is sufficient to increase resistance to hydroxyurea in transfected cells. AB - Ribonucleotide reductase (RR) is a rate-limiting enzyme in DNA synthesis. The enzyme consists of two subunits, M1 and M2. Hydroxyurea (HU) is an M2-specific inhibitor. It has been shown that a HU-resistant clone derived from stepwise exposure to HU overexpresses the M2 mRNA and the RR protein (Y. Yen et al., Cancer Res., 54: 3868-3691, 1994). In this study, we established stable clones by transfecting human KB cells with the cDNA of human wild-type RR in which each subunit was overexpressed by a SV40 promoter. The mammalian cell expression vector ph beta APr-1 was used for constructing M1, M2, and M1/M2 subunit cDNA. The transfected cells were selected with G418. The clones designated M2-D, M1-D, X-D, and KB-V represent transfectant clones which contain M2 cDNA, M1 cDNA, M1/M2 cDNA, and vector alone, respectively. The parental KB cells and clones containing vector plasmid KB-V express equally low amounts of M2 and M1 mRNA from the endogenous genes. The expression of M2 mRNA and M1 mRNA is elevated 2-3 fold in the X-D transfectants. M2-D clone demonstrated a 6-fold higher M2 mRNA level although the M1 mRNA expression remains the same as parental cells. M1-D transfectants have a 3-fold increase in M1 mRNA expression relative to parental cells, but reveal no alteration of M2 mRNA. Southern analysis of genomic DNA suggested the incorporation of the plasmid into the genome. The X-D clone revealed both integration of the M2 and M1 gene while the M2-D clone only showed M2 gene integration. The M1-D clone revealed M1 gene integration relative to the parental cells. The Western blot of M2 protein showed a 3-fold increase in the X D and M2-D clones whereas the M2 protein level in M1-D was the same as it was in parental cells. The M1 protein was increased 3-fold in X-D and 1.5-fold in M1-D over that of parental cells. However, lower M1 protein levels were identified in the M2-D clone. The specific activity of the RR enzyme from each transfectant showed a 3-fold increase in both the X-D and M2-D clones and slightly increased in M1-D clone over that of parental cells. However, X-D and M2-D both demonstrated a 3-fold increase in resistance to HU as compared to M1-D which showed the same sensitivity as the parental enzyme.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7882332 TI - Gains and losses of DNA sequences in osteosarcomas by comparative genomic hybridization. AB - Our aim was to identify chromosomal regions that are likely to harbor previously unknown genes with an important role in the genesis of osteosarcoma. Comparative genomic hybridization was used to screen for losses and gains of DNA sequences along all chromosome arms in 11 tumors. Extensive genetic aberrations, with an average of 11 changes/tumor (range, 1-20), were found in 10 of the 11 specimens. High level amplifications of small chromosomal regions were detected in eight tumors. These involved the 12q12-q13 region (known to contain the SAS-MDM2 locus) and several previously unreported amplification sites such as 17p11-p12, 3q26, and Xq12. When all DNA sequence gains were evaluated, the gains at 8q and Xp were most common (45%). The most common losses of DNA sequences were seen at 2q, 6q, 8p, and 10p (36%). In conclusion, despite the very complex pattern of genetic changes in osteosarcomas, certain chromosomal regions appear to be affected more often than others. Most of these regions have not previously been reported to be implicated in osteosarcomas and may thus highlight locations of novel genes with an important role in the development and progression of these tumors. PMID- 7882333 TI - Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin. AB - We developed previously a resistant cell line, CEM/C2, from the human leukemia cell line CCRF-CEM by stepwise selection in camptothecin. This cell line is 974 fold more resistant to camptothecin than parental cells. Resistance is only partially explained by 2-fold reductions in topoisomerase I protein and mRNA levels. We further investigated biochemical and molecular features of topoisomerase I in the resistant cell line. Sequence analyses of the top1 cDNA from CEM/C2 identified mutations corresponding to two amino acid substitutions, Met370Thr and Asn722Ser. Asn722Ser is next to the catalytic Tyr723 in a region highly conserved among type I eukaryotic DNA topoisomerases. Recombinant top1 with the corresponding substitution was found to be catalytically active and resistant to camptothecin. These results indicate that camptothecin resistance of CEM/C2 is due to the mutation Asn722Ser and strongly suggest that the asparagine immediately flanking the catalytic tyrosine is important for the camptothecin action. PMID- 7882334 TI - Frequent loss of heterozygosity in human primary squamous cell and colon carcinomas at 7q31.1: evidence for a broad range tumor suppressor gene. AB - Consistent deletions and loss of heterozygosity (LOH) in polymorphic markers in a determinate chromosomal fragment are known to be indicative of a closely mapping tumor suppressor gene. Deletion of the long arm of chromosome 7 is a frequent trait in many kinds of human primary tumors. We studied LOH of 14 markers on chromosome 7q in order to determine the location of a putative tumor suppressor gene in human primary squamous cell carcinoma of the head and neck and in human primary colon carcinomas. Samples were obtained from 18 primary squamous cell carcinomas of the head and neck and 18 primary colon carcinomas surgically removed from patients at the Fox Chase Cancer Center. Loss of heterozygosity was studied performing PCR amplifications of a set of 14 CA microsatellite repeats encompassing 7q21-qter. Of 18 squamous cell carcinomas of the head and neck cases studied, 12 had LOH at one or more loci on 7q. Fifty-three percent of 15 informative cases had LOH of the CA microsatellite dinucleotide repeat marker D7S522 at 7q31.1-7q31.2. Eleven of 18 colon carcinoma cases had LOH of one or more markers assayed, and the maximum LOH (80% of 10 informative cases) was at D7S522. Distributions of percentage of LOH in both tumor types were normally distributed around microsatellite D7S522. The high incidence of LOH in both tumor types studied suggests that a tumor suppressor gene relevant to the development of epithelial cancers is present on the 7q31.1-31.2, confirming our previous functional evidence for a tumor suppressor gene on chromosome 7. PMID- 7882335 TI - Replacement of the p16/CDKN2 gene suppresses human glioma cell growth. AB - The p16/CDKN2 gene has many features of a growth suppressor gene: it maps to 9p21, a frequent region of loss of heterozygozity in a variety of tumor types; it encodes an inhibitor of cyclin-dependent kinase 4; and its homozygous deletion is common in tumor-derived cell lines. However, the lower frequency of alteration of the gene in primary tumor tissue as compared to the cognate tumor cell lines has brought this interpretation into question. We have assessed the growth suppressive function of p16/CDKN2 by gene transfer. The introduction of full length p16/CDKN2 cDNA caused marked growth suppression in p16/CDKN2-null human glioma cells, but was without significant effect in those cells with endogenous wild-type p16/CDKN2 alleles. These results provide functional evidence in support of the hypothesis that the p16/CDKN2 gene is a functional growth suppressor gene, at least in gliomas. PMID- 7882336 TI - Deletion cartography around the D13S25 locus in B cell chronic lymphocytic leukemia and accurate mapping of the involved tumor suppressor gene. AB - The presence of an unidentified tumor suppressor gene on the long arm of chromosome 13 which could be involved in the development of B cell chronic lymphocytic leukemia has been suspected because of frequent deletions of the locus D13S25 which lies 1.6 cM telomeric to the retinoblastoma gene. In order to accurately map this gene, cells from 25 B cell chronic lymphocytic leukemia tumors have been analyzed for allelic loss using a panel of microsatellite markers located in this region. These markers, which stretch from the retinoblastoma gene to the Wilson disease gene, have been ordered for their rank from centromere to telomere. In addition to the data obtained from deletion pattern of these markers, results from preliminary pulse-field electrophoresis studies enable us to redefine the minimal deleted area from more than 1 cM to 280 kilobase around D13S25. PMID- 7882337 TI - Aberrant expression of p53 or the epidermal growth factor receptor is frequent in early bronchial neoplasia and coexpression precedes squamous cell carcinoma development. AB - New strategies are needed for the detection and treatment of lung cancer and must derive from a fuller understanding of lung carcinogenesis. Frequent molecular genetic abnormalities occur in non-small cell lung cancer (NSCLC), but little is known about which of these precede an invasive carcinoma. We examined the expression of p53, epidermal growth factor receptor (EGFR), and transforming growth factor alpha, the most common molecular genetic abnormalities in NSCLC, in preneoplastic bronchial lesions. Primary NSCLC and associated bronchial lesions were identified by retrospective review of resected tumors at this center. Expression in the invasive carcinomas, the associated bronchial lesions, and normal lung were contrasted using immunohistochemistry. Thirty-four NSCLC associated with 62 bronchial lesions were identified. The invasive tumors included 15 squamous cell carcinomas (SCCs) and 19 non-SCCs. Bronchial lesions included areas of squamous metaplasia (n = 14), inflammatory atypia (n = 19), dysplasia (n = 17), and carcinoma in situ (n = 12). Nineteen (56%) NSCLC and 10 (16%) bronchial lesions exhibited aberrant p53 immunostaining, whereas 18 (53%) NSCLC and 30 (48%) bronchial lesions showed abnormal EGFR immunostaining. Positive staining for transforming growth factor alpha was seen in 16 (47%) NSCLC but occurred inconsistently in the bronchial lesions and in normal bronchial epithelium. Only bronchial lesions associated with squamous cell carcinomas exhibited staining for p53. Aberrant EGFR expression was not associated with a specific type of invasive carcinoma or with specific preneoplastic lesions, although there was a trend toward increased expression in dysplasia and carcinoma in situ relative to metaplasia and atypia. All but one of the NSCLC simultaneously showing aberrant p53 and EGFR staining were SCC. We conclude that: (a) transforming growth factor alpha is variably expressed in normal respiratory epithelium as well as reactive and preneoplastic bronchial lesions; (b) p53 expression is seen in preneoplastic bronchial lesions but is not present in reactive or metaplastic epithelium; (c) aberrant EGFR expression occurs in both reactive and preinvasive bronchial lesions and may be an early marker of neoplastic transformation; and (d) the simultaneous aberrant expression of EGFR and p53 occurs predominantly in SCC and their associated bronchial lesions. These findings indicate that aberrant expression of p53 or the EGFR is frequent in bronchial neoplasia, and coexpression may predispose to the development of squamous cell carcinomas of the lung. PMID- 7882338 TI - Substrate balances across colonic carcinomas in humans. AB - To investigate the utilization of nutrients by malignant tumors in humans, the balances of energy-yielding substrates and amino acids across colonic carcinomas were assessed in 17 patients during surgery. Blood samples were taken from an artery and the main tumor-draining vein, which was also used for determining tumor blood flow (direct venous outflow technique). Additionally, the substrate exchange by peripheral tissues was studied (femoral arteriovenous differences, venous occlusion plethysmography). Mean blood flow was greater in the carcinomas than in the leg tissues (43.2 versus 2.5 ml/100 ml/min; P < 0.001). There was a negative correlation between tumor blood flow and tumor weight (r = -0.87; P < 0.001). Glucose net uptake and lactate release by the malignancies exceeded the peripheral exchange rates 30- and 43-fold, respectively (mean values different at P < 0.001). The molar ratio of lactate output to glucose consumption was 0.78 in the tumors and 0.48 in the leg tissues (P < 0.05). Regarding free fatty acid and ketone body balances, no significant tumor-periphery differences were noted. The carcinomas utilized branched chain amino acids and serine, while alanine and, in particular, ammonia were released in large amounts. Net glutamine retention was not consistently observed. It is concluded that the energy metabolism of human colonic carcinomas relies predominantly on glucose, with fat-derived calories making no appreciable contribution. The impaired nutritive perfusion of malignant tumors appears to favor glycolysis and to limit both glucose oxidation and glutaminolysis. The present study has shown that the procedure chosen for the assessment of trans-tumor substrate flux rates is a workable and valid model for analyzing metabolic balances across human colonic cancers in vivo. PMID- 7882339 TI - Alterations of c-myc expression by antisense oligodeoxynucleotides enhance the induction of apoptosis in HL-60 cells. AB - This study was designed using c-myc antisense oligodeoxynucleoside phosphorothioate (AS PS-ODN) to evaluate how alterations of c-myc expression in HL-60 human myeloid leukemia cells could influence the induction of apoptosis. Unexpectedly both the continuous down-regulation of c-myc expression caused by exposure to c-myc AS PS-ODN and up-regulation after its withdrawal influenced apoptosis. We found that continuous suppression of c-myc expression by 10 microM c-myc AS PS-ODN could decrease the proliferation of HL-60 cells to approximately 60% of the control growth after 3 days of suspension culture, and when assessed morphologically the percentage of cells undergoing apoptosis was 3.5%. Evidence either of cell cycle arrest or cell cycle prolongation was not detected. It is likely that apoptosis induced by the sustained down-regulation of c-myc expression with AS PS-ODN treatment was solely sufficient to explain the inhibition of cell proliferation. Up-regulation of c-myc expression was observed within 1 h after c-myc AS PS-ODN withdrawal. This up-regulation further enhanced induction of apoptosis and involved up to 32% of the cells. These results suggest that while the continuous suppression of c-myc expression caused a constant effect on the induction of apoptosis, its abrupt up-regulation could rapidly drive a considerable number of HL-60 cells into the apoptotic pathway. PMID- 7882340 TI - Biphenotypic sarcomas with myogenic and neural differentiation express the Ewing's sarcoma EWS/FLI1 fusion gene. AB - Accurate diagnosis of primitive childhood sarcomas continues to be a formidable problem because these malignancies generally demonstrate very little morphological evidence of their tissue of origin. One of these tumor classes, the Ewing's sarcoma family of peripheral primitive neuroectodermal tumors (pPNETs), are thought to have a neural histogenesis based on evidence of neuroectodermal differentiation. Greater than 95% of pPNETs carry t(11;22) or t(21;22) chromosomal translocations which fuse the EWS gene from chromosome 22q12 in-frame with either FLI1 from chromosome 11q24 or ERG from chromosome 21q22. The pPNETs are considered to be histogenetically distinct from rhabdomyosarcomas, myogenic tumors lacking these EWS gene fusions and hypothesized to derive from immature skeletal muscle precursors. In the present study, we describe a unique set of childhood soft tissue sarcomas that show both neural and myogenic differentiation. These biphenotypic tumors express myogenic regulatory factors and muscle-specific antigens and also show neuroectodermal differentiation with ultrastructural evidence of neurosecretory granules and expression of neural associated genes. Northern analysis and reverse transcriptase PCR reveal expression of EWS/FLI1 gene fusions in all biphenotypic sarcomas analyzed. Chimeric EWS/FLI1 transcripts and fusion proteins in these tumors are identical to those described for pPNETs. Our results provide evidence for a class of biphenotypic childhood sarcomas with myogenic and neural differentiation and suggest that these tumors may be related to the Ewing's sarcoma family of pPNETs. PMID- 7882341 TI - Characterization of a messenger RNA polynucleotide vaccine vector. AB - We have constructed mRNA transcripts encoding luciferase and human carcinoembryonic antigen (CEA) which are capped, polyadenylated, and stabilized by human beta-globin 5' and 3' untranslated regions. The mRNA construct encoding human CEA directed CEA expression in mouse fibroblasts in vitro following liposome-mediated transfection. The luciferase encoding mRNA transcripts mediated luciferase expression in vivo following i.m. injection. Based on the demonstration of protein expression in vitro and in vivo, the feasibility of using such a vector as a tumor vaccine was examined. In this pilot study, seven mice received 50 micrograms mRNA transcripts encoding CEA twice weekly for 5 weeks by i.m. injection followed by challenge with syngeneic, CEA-expressing tumor cells. This dose and schedule "primed" an immune response to CEA. Five of seven mRNA-immunized mice demonstrated anti-CEA antibody 3 weeks after tumor challenge whereas control mice had no evidence of antibody response. This strategy might be particularly useful to induce an immune response to a proto oncogene product or growth factor which poses a risk of inducing malignant transformation consequent to prolonged protein expression. PMID- 7882342 TI - Decreased tumor formation in 7,12-dimethylbenzanthracene-treated stromelysin-1 transgenic mice is associated with alterations in mammary epithelial cell apoptosis. AB - To determine the role of a specific member of the metalloproteinase family, stromelysin-1, in mammary carcinogenesis and tumor progression, transgenic mice expressing activated rat stromelysin-1 under the control of the mouse mammary tumor virus promoter/enhancer were treated with the carcinogen 7,12 dimethylbenzanthracene (DMBA) to induce mammary tumors. Surprisingly, the expression of stromelysin-1 during the time of DMBA treatment reduced the number of mice developing mammary tumors, in particular adenoacanthomas, from 65 to 32% (P = 0.02). In contrast, when transgenic mice expressing both transforming growth factor alpha and stromelysin-1 under the control of the mouse mammary tumor virus long terminal repeat were treated with DMBA, there was no significant difference in the number of mice that developed tumors compared to transforming growth factor alpha controls. A 4-fold increase in the number of apoptotic cells was detected in stromelysin-1 transgenic mice compared to littermate controls at the time of DMBA administration, suggesting that the reduction in DMBA-induced tumorigenicity is likely to be due, at least in part, to an increased rate of cell turnover in stromelysin-1 transgenic mice. When malignant adenocarcinomas developed in the stromelysin-expressing mice, there was no detectable alteration in the extent of invasion or in the metastatic potential of these tumors compared to tumors from control mice. These results suggest that the expression of a single metalloproteinase, stromelysin-1, is insufficient for the progression of mammary adenocarcinomas to an invasive and metastatic phenotype, but that matrix degradation by metalloproteinases can alter basic processes of cell proliferation and apoptosis. PMID- 7882343 TI - Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. AB - Thymidylate synthase (TS) is the target enzyme for 5-fluorouracil (5-FU). We have correlated TS protein and gene expression with the response in patients with colorectal (n = 9) and gastric cancer (n = 12) treated with infusional 5-FU plus leucovorin (LV) or infusional 5-FU/LV and cisplatin, respectively. TS protein expression was analyzed by Western blot using TS106 monoclonal antibody and densitometry scanning. TS gene expression was measured by PCR analysis using beta actin as an internal standard and expressed as a TS:beta-actin mRNA ratio. A close linear relationship was noted between TS protein expression and TS gene expression (r2 = 0.60) for the 21 tumor samples analyzed. TS immunohistochemical staining on 15 of the 21 samples revealed that the TS staining intensity correlated closely with TS protein and mRNA expression. In two biopsy samples, TS protein levels and TS gene expression did not correlate; however, one of these exhibited a focal TS staining pattern. Both the TS protein level and TS gene expression were significantly associated with response to 5-FU-based therapy. Patients with responsive disease had a mean TS protein level of 0.17 +/- 0.03 arbitrary units (range, 0.05 to 0.38), whereas in patients whose tumors did not respond, the mean TS protein level was significantly higher 0.60 +/- 0.09 (range, 0.06 to 1.01; P < 0.01). A similar pattern was noted with TS gene expression. In patients with responsive disease, the mean TS:beta-actin gene ratio was 1.36 +/- 0.3 (range, 0.5-3.3 x 10(-3). In contrast, biopsies from patients with unresponsive disease had a mean TS:beta-actin gene ratio of 15.4 +/- 2.6 x 10(-3) (range, 2.7-35.9; P < 0.01). TS protein and TS mRNA expression are highly correlated, and each predict for response to 5-FU/LV-based chemotherapy in patients with colorectal and gastric cancer. PMID- 7882344 TI - Transforming growth factor beta-induced activation of cyclin E-cdk2 kinase and down-regulation of p27Kip1 in C3H 10T1/2 mouse fibroblasts. AB - Transforming growth factor (TGF-beta)-stimulated induction of DNA synthesis is preceded by the activation of cyclin E/cyclin-dependent kinase (cdk)2 kinase in late G1 in C3H 10T1/2 mouse fibroblasts. TGF-beta has no effect on the steady state level of cdk4, while having only a modest inductive effect on cyclin D1 expression. TGF-beta stimulation does, however, lead to the striking down regulation of p27Kip1 expression during G1 in a manner consistent with the timing of cyclin E-cdk2 activation. Coimmunoprecipitation analysis reveals that the amount of p27Kip1 in complexes with the cdk2 catalytic subunit is drastically reduced at the time in late G1 when cyclin E-cdk2 activity is maximal. These data indicate that cyclin E-cdk2 is inhibited by p27Kip1 in the growth-arrested state and that TGF-beta relieves this inhibition by down-regulating the steady-state level of the p27Kip1 inhibitor protein, thus reducing the level of inhibitor present in complexes with cdk2. PMID- 7882345 TI - Plasminogen activator inhibitor-2: prognostic relevance in 1012 patients with primary breast cancer. AB - The antigen levels of urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor (PAI) 1, as detected in tumor extracts by ELISA, have been reported to be correlated with a poor prognosis in primary breast cancer. In the present study we have characterized a novel PAI-2-specific ELISA, designed to measure PAI-2 antigen levels in tumor cytosols. We determined PAI-2 antigen levels along with those of uPA and PAI-1 in 1012 routinely prepared tumor cytosols of patients with primary breast cancer (median follow-up, 71 months). In the overall population there was no significant association between the level of PAI-2 and prognosis, while in tumors with high uPA values, PAI-2 (test for trend) was associated with a prolonged relapse-free survival, metastasis-free survival, and overall survival (for all analyses, P < 0.02). In Cox's multivariate analysis for relapse-free survival, metastasis-free survival, and overall survival in tumors with high uPA values (including patient's age, menopausal status, lymph node status, tumor size, estrogen and progesterone receptor status, uPA, and PAI-1), PAI-2 either dichotomized or, as a continuous variable, was independently associated with a favorable relapse-free survival, metastasis-free survival, and overall survival. We conclude that the PAI-2 specific ELISA described herein is well suited for the measurement of PAI-2 levels in cytosols routinely prepared for analysis of steroid hormone receptors. We speculate that PAI-2 may serve as an inhibitor for uPA in human primary breast cancers. PMID- 7882346 TI - Occurrence of microsatellite instability in gastric carcinoma is associated with enhanced expression of erbB-2 oncoprotein. AB - To investigate the molecular mechanism of gastric carcinogenesis, we examined simultaneously the frequency of microsatellite instability and the immunoreactivities to ras, erbB-2, and p53 in 42 gastric adenocarcinoma tissues. Microsatellite instability, measured by DNA replication error, was detected in 33.3% (14/42) of patients with gastric carcinoma while positive immunostaining was demonstrated in 3.1% (1/32) for ras, 40.5% (17/42) for erbB-2, and 28.6% (12/42) for p53. There was no statistical difference between the intestinal type and the diffuse type of carcinoma with respect to microsatellite instability, ras, or erbB-2 expression. The expression of p53 occurred more frequently in the intestinal type of carcinoma (41.7%, 10/24) than in the diffuse type of carcinoma (11.1%, 2/18; P < 0.01). There was no association between microsatellite instability and ras or p53 expression, while enhanced expression of erbB-2 occurred more frequently in carcinomas with microsatellite instability (64.3%, 9/14) than in those without microsatellite instability (28.6%, 8/28; P < 0.05). Such a strong association between microsatellite instability and erbB-2 oncogene may be responsible for the increase of other oncogenic mutations and tumor progression in gastric carcinogenesis. PMID- 7882347 TI - A mutant p21 cyclin-dependent kinase inhibitor isolated from a Burkitt's lymphoma. AB - The growth arrest mediated by p53 is caused at least in part by the p53 mediated expression of p21 (p21waf1/Cip1). Since only one-third of primary Burkitt's lymphomas (BL) demonstrate mutations in the p53 gene, we examined the structural integrity of the p21 coding region by single-strand conformational polymorphism and DNA sequence analysis to determine the extent to which this gene is mutated in BL. Of 34 BLs analyzed, a frequent change (38%) at codon 31 that replaced Ser with Arg was found in 13 samples, 10 of which were from Africa. This change at codon 31 is also detected in peripheral blood DNA from normal subjects and may thus represent a polymorphism. One BL cell line, DH978, carried a change at codon 63: Phe to Leu. This mutation was heterozygous, and both the wild-type and the mutated p21 mRNA were expressed in the tumor cell line. By transfection experiments, the mutant p21 was less efficient in suppressing clonogenicity than wild-type p21. To our knowledge, this is the only mutation described in p21. The availability of this mutant p21 should further help in functional studies of p21. PMID- 7882348 TI - Involvement of CDKN2 (p16INK4A/MTS1) and p15INK4B/MTS2 in human leukemias and lymphomas. AB - CDKN2 (p16INK4A/MTS1) and p15INK4B/MTS2 have been shown recently to be potent inhibitors of the cyclin D/cyclin-dependent kinase 4 complex. Both genes are candidates for the putative tumor suppressor gene located at chromosome 9p21. We examined a series of 14 hematopoietic cell lines and 117 primary lymphoid tumors for deletion and mutation of these genes. The primary tumors included 65 T-cell malignancies and 52 B-cell malignancies. The cell line study revealed 4 of 4 T ALL lines to have homozygous deletions of CDKN2. Two of the 4 lines also showed homozygous deletions of MTS2, while the remaining 2 lines retained both MTS2 alleles. In the primary tumors, homozygous deletions of both CDKN2 and MTS2 were found in 35% of the T-ALL/lymphoblastic lymphoma (8 of 23). Homozygous deletions of both genes also occurred in 1 of 3 precursor B-ALLs. PCR-single strand conformational polymorphism analysis of CDKN2 exons 2 and 3 and MTS2 exon 2 failed to demonstrate mutations in either CDKN2 or MTS2 in any of the T- or B cell malignancies, with two possible exceptions. These results are consistent with a role for CDKN2 and/or MTS2 in the pathogenesis of some lymphoid leukemia/lymphomas, particularly in T-ALL/lymphoblastic lymphoma. PMID- 7882349 TI - Alternatively spliced variants of prostate-specific membrane antigen RNA: ratio of expression as a potential measurement of progression. AB - We examined expression of prostate-specific membrane antigen (PSM) mRNA in normal prostate using reverse transcription-PCR and sequencing. An alternatively spliced variant, PSM', along with the previously described PSM form, was found in normal prostate. PSM' cDNA is shorter (2387 nucleotides) than PSM (2653 nucleotides). The cDNAs are identical except for a 266-nucleotide region near the 5' end of PSM cDNA (nucleotide 114-380) that is absent from PSM'. This deleted region includes the translation initiation codon and codons for the putative transmembrane domain of PSM. Thus, PSM' RNA codes for a protein that has no apparent signal sequence. We verified the existence of spliced mRNA variants in human primary tissue specimens by RNase protection assay. In LNCaP human prostatic cancer cells and in primary prostate tumors, PSM is the dominant form. In contrast, normal human prostate expressed more PSM' than PSM. Benign prostatic hypertrophy samples showed about equal expression of both variants. We quantified the relative expression of each variant by densitometry and compiled a tumor index, which is the ratio of PSM:PSM' level. LNCaP has an index ranging from 9-11, carcinoma of the prostate from 3-6, benign prostatic hypertrophy from 0.75-1.6, and normal prostate from 0.075-0.45. The index reflects the increased expression of PSM over PSM' following the progression from normal to tumor state. This tumor index may be a useful indicator for the measurement of tumor progression. PSM and PSM' may be functionally different proteins as a result of differences in structure or cellular location. We are investigating the prevalence of one form over the other and how it may influence tumor progression. PMID- 7882350 TI - Increased prevalence of K-ras oncogene mutations in lung adenocarcinoma. AB - Reported estimates of ras mutation prevalence in lung adenocarcinoma of 15-24% may be underestimates because of the insensitivity of the assays used. We have devised a rapid, non-radioactive assay for ras mutations, which detects 1 mutant allele/10(3) normal alleles and have used it to study DNA isolated from 53 lung tumor samples (including 28 adenocarcinomas) previously analyzed by PCR/allele specific oligonucleotide hybridization, which is less sensitive. We detected mutations in 13 of 28 samples, including 7 not detected by PCR/allele specific oligonucleotide hybridization. We also found ras mutations in 14 of 25 previously unstudied samples (56%). Our results indicate that the prevalence of K-ras codon 12 mutations in lung adenocarcinoma is higher than previously reported; thus, ras mutations may be more clinically useful as molecular markers for lung cancer than has been appreciated. PMID- 7882352 TI - Transforming growth factor beta and cell cycle regulation. PMID- 7882351 TI - Mutations in the p16INK4/MTS1/CDKN2, p15INK4B/MTS2, and p18 genes in primary and metastatic lung cancer. AB - We examined the genomic status of cyclin-dependent kinase-4 and -6 inhibitors, p16INK4,p15INK4B, and p18, in 40 primary lung cancers and 31 metastatic lung cancers. Alterations of the p16INK4 gene were detected in 6 (2 insertions and 4 homozygous deletions) of 22 metastatic non-small cell lung cancers (NSCLCs; 27%), but none were detected in 25 primary NSCLCs, 15 primary small cell lung cancers (SCLCs), or 9 metastatic SCLCs, indicating that mutation in the p16INK4 gene is a late event in NSCLC carcinogenesis. Although three intragenic mutations of the p15INK4B gene were detected in 25 primary NSCLCs (12%) and five homozygous deletions of the p15INK4B gene were detected in 22 NSCLCs (23%), no genetic alterations of the p15INK4B gene were found in primary and metastatic SCLCs. The p18 gene was wild type in these 71 lung cancers, except 1 metastatic NSCLC which showed loss of heterozygosity. We also examined alterations of these three genes and expression of p16INK4 in 21 human lung cancer cell lines. Alterations of the p16INK4 and p15INK4B genes were detected in 71% of the NSCLC cell lines (n = 14) and 50% of the NSCLC cell lines (n = 14), respectively, but there were none in the 7 SCLC cell lines studied. No p18 mutations were detected in these 21 cell lines. These results indicate that both p16INK4 and p15INK4B gene mutations are associated with tumor progression of a subset of NSCLC, but not of SCLC, and that p15INK4B mutations might also be an early event in the molecular pathogenesis of a subset of NSCLC. PMID- 7882353 TI - Purification and characterization of a lipid-mobilizing factor associated with cachexia-inducing tumors in mice and humans. AB - A scheme is described for the purification of a lipid-mobilizing factor from a cachexia-inducing murine tumor (MAC16) using a combination of ion exchange (Mono Q), exclusion (Superose), and hydrophobic (C8) chromatography. This process yields an active material with an apparent molecular weight of 24,000 with an overall purification of 3,500 from the tumor homogenate and representing 0.005% of the total protein present. The material tends to aggregate to high molecular mass, is acidic (pI < 4), and displays heterogeneity of charge as evidenced by a broad elution profile on ion exchange and exclusion chromatography and multiple peaks on hydrophobic columns. The purified material was heat and alkali (pH 10.4) labile and activity could be completely inhibited by sulfatase, suggesting that the negative charge could arise from sulfate residues. There was no evidence that the material possessed triglyceride lipase activity. Animals transplanted with the MAC16 tumor and with a delayed weight loss contained in their serum antibodies that recognized a M(r) 24,000 band on Western blots. This material copurified with the lipid-mobilizing factor. Such antibodies were not present in the serum of mice transplanted with the MAC13 tumor, which does not induce cachexia, suggesting that the antibodies were directed to the induction of cachexia rather than the tumor itself. Urine from patients with cancer cachexia also contained a lipid-mobilizing factor which adhered to DEAE-cellulose and gave an apparent M(r) of 24,000 by exclusion chromatography. Western blotting using serum from MAC16 tumor-bearing animals showed the presence of a band of M(r) 24,000 in such fractions, which was not detected using serum from mice bearing the MAC13 tumor. This band was not present in Western blots of urine from normal subjects. The fact that serum from mice bearing the MAC16 tumor can detect the human lipid-mobilizing activity suggests a high degree of structural similarity between the two and raises the possibility that cachexia in humans may be caused by the same species as in the mouse. PMID- 7882355 TI - Genetic and enzymatic evidence for Lewis enzyme expression in Lewis-negative cancer patients. AB - It has been observed that the frequency of individuals with Lewis-negative erythrocytes is significantly higher in cancer patients than in healthy controls. In this study, 20 of the 66 (30.3%) patients with various cancers were typed as Lewis negative from their erythrocytes, while the same frequency in healthy controls was 11.1%. These 20 patients were divided into three groups based on the presence of Lewis blood group antigens and alpha 1-->4-fucosyltransferase in their salivas: group I, 6 patients who had both Lewis antigens and alpha 1-->4 fucosyltransferase activity; group II, 8 patients who had no Lewis antigens but possessed alpha 1-->4-fucosyltransferase activity; group III, 6 patients who had neither Lewis antigens nor alpha 1-->4-fucosyltransferase activity. The genotyping of Le genes by the PCR-RFLP methods, which have been developed and established by us recently, demonstrated that all 14 patients from groups I and II possess Le gene homozygously (Le/Le) or heterozygously (Le/le), whereas all 6 patients from group III were le/le homozygotes. Only the 6 patients from group III were identified as the genuine Lewis-negative individuals. The immunohistochemical staining of the colorectal tumors also showed that the Lewis antigens could be detected on the tumors from groups I and II but not from group III. PMID- 7882354 TI - Chemoprevention of colon carcinogenesis by sulindac, a nonsteroidal anti inflammatory agent. AB - Epidemiological and laboratory animal model studies have suggested that nonsteroidal anti-inflammatory drugs reduce the risk of development of colon cancer. The present study was designed to investigate the chemopreventive action of 160 and 320 ppm (equivalent to 40 and 80% maximum tolerated doses) sulindac, a nonsteroidal anti-inflammatory drug, fed during initiation and postinitiation stages and 320 ppm sulindac fed during promotion/progression stages of azoxymethane-induced colon carcinogenesis in male F344 rats. Also investigated was the modulating effect of this agent on the colonic mucosal and tumor phospholipase A2, phosphatidylinositol-specific phospholipase C, lipoxygenase, and cyclooxygenase activities. At 5 weeks of age, groups of male F344 rats were fed control diet or diets containing 160 and 320 ppm of sulindac. At 7 weeks of age, all animals except those in the vehicle-treated groups were given two weekly s.c. injections of azoxymethane at a dose rate of 15 mg/kg body weight/week. Animals intended for tumor promotion/progression study were administered 320 ppm of sulindac in diet starting at 14 weeks after a second azoxymethane treatment. All animals continued on their respective dietary regimen until the termination of the experiment at 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. Colonic mucosa and tumors were analyzed for phospholipase A2, phosphatidylinositol-specific phospholipase C, prostaglandin E2, cyclooxygenase, and lipoxygenase activities. The levels of sulindac and its metabolites in stomach, cecal, and fecal contents and in serum were analyzed. The results indicate that dietary sulindac at 160 and 320 ppm levels inhibited the incidence of invasive and noninvasive adenocarcinomas of the colon (P < 0.01 0.001) as well as their multiplicity (P < 0.01-0.0001) in a dose-dependent manner. Also, feeding sulindac during promotion/progression stages significantly suppressed the incidence (P < 0.0001) and multiplicity (P < 0.0001) of colonic adenocarcinomas. Dietary sulindac also suppressed the colon tumor volume by > 52 62% compared to the control diet. Dietary sulindac significantly decreased the activities of phosphatidylinositol-specific phospholipase C (32-51%) and levels of prostaglandin E2 (> 40%) in the colonic mucosa and tumors, but it had no significant (P > 0.05) effect on phospholipase A2 activity. The formation of cyclooxygenase metabolites, particularly prostaglandin E2, prostaglandin F2 alpha, prostaglandin D2, 6-ketoprostaglandin F1 alpha, and thromboxane B2, and lipoxygenase metabolites such as 8(S)- and 12(S)-hydroxyeicosatetraenoic acids were significantly reduced in colonic mucosa and tumors of animals fed 320 ppm sulindac.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7882356 TI - Expression and secretion of the beta subunit of human chorionic gonadotropin by bladder carcinoma in vivo and in vitro. AB - Expression and secretion of the beta subunit of human chorionic gonadotropin (hCG) by bladder carcinoma cell lines were investigated in vitro and in vivo. As an in vitro study, immunoreactive hCG beta (IR-hCG beta) secreted into the culture media of two bladder transitional cell lines (KoTCC-1 and HT-1197) was analyzed using three kinds of enzyme immunoassays which were specific for intact hCG, free hCG beta, and beta core fragment (beta-CF). Both of the cell lines were determined to secrete IR-hCG beta into the media, which consisted principally of free hCG beta, but detectable levels of intact hCG and beta-CF were not present in the media. Northern blot analysis revealed that the hCG beta gene was expressed in both KoTCC-1 and HT-1197 cells where the sizes of mRNA from these cells were smaller than those from placental and NJG choriocarcinoma cells. As an in vivo study, distribution of IR-hCG beta was analyzed in the tumor tissues, sera, and urine of the mice and the rats transplanted with KoTCC-1 cells. By the immunohistochemical study, the IR-hCG beta was clearly observed in transitional cell carcinoma cells of the transplanted tumor. High levels of IR-hCG beta were detected in both the serum and urine from the animals, but there were quantitative and qualitative differences between serum and urinary IR-hCG beta. Quantitatively, the concentrations of IR-hCG beta in the urine were consistently much higher than those in the serum. Qualitatively, free hCG beta was exclusively detected in the serum whereas high levels of beta-CF in addition to free hCG beta were found in the urine. Intact hCG could not be detected in the serum and urine. These distributions of IR-hCG beta in the animals transplanted with KoTCC-1 cells were completely analogous to those in a patient with hCG beta-producing bladder carcinoma. The present study shows that the same metabolic pathway of IR-hCG beta is operating in mice and rats as in humans, indicating that IR-hCG beta found in patients with bladder carcinoma originates from the tumor and it may be recognized as a tumor marker when beta-CF is measured in the patient's urine. PMID- 7882357 TI - Racial disparity in the association of p53 gene alterations with breast cancer survival. AB - A significant black/white difference in breast cancer prognosis has been observed in the United States. Alterations of p53 tumor suppressor gene in breast cancer have been associated with poor prognosis. This study was designed to test the hypothesis that p53 gene alterations are related to the difference in prognosis between black and white breast cancer patients. Formalin-fixed paraffin-embedded breast tissue blocks were available from 45 black and 47 white patients for PCR single strand conformation polymorphism analysis and DNA sequencing. The types of p53 gene alterations were compared between blacks and whites. Associations between p53 gene alterations and survival were also evaluated. Three missense, 2 nonsense, 1 microdeletion, 1 intron, and 4 silent mutations were detected in blacks, while 7 missense, 1 microdeletion, 1 silent mutation, and 3 polymorphisms were observed in whites. Among the point mutations, G:C to A:T transitions at non CpG sites were found in 80.0% of blacks (8 of 10) and 62.5% of whites (5 of 8). Significantly poorer survival associated with p53 gene alterations was observed for blacks (P = 0.012), but not for whites. Black patients with p53 alterations had a significant 4-5-fold excess risk of death from breast cancer than those without p53 alterations. Adjustment for stage, age, tumor histopathology, receptor status, and adjuvant treatment did not change the excess risk. The findings suggest that the types of p53 gene alterations may contribute to the racial difference in breast cancer survival. PMID- 7882358 TI - Molecular pharmacology of hepsulfam, NSC 3296801: identification of alkylated nucleosides, alkylation site, and site of DNA cross-linking. AB - We have determined that hepsulfam, in common with its structural homologue busulfan, alkylates both free guanosine and GMP in DNA at the 7 nitrogen. Mass spectral analysis of the products of the reaction of hepsulfam with guanosine has identified the mono- and bis-alkylated guanosine adducts. UV spectrophotometry and mass spectrometry were used to confirm that alkylation occurred at the 7 nitrogen by following the formation of the formamidopyrimidyl form of the hepsulfam-guanosine adduct at high pH. We have also isolated and identified 1 guanyl,7-hydroxyheptane, 1-guanyl,7-sulfamylheptane, and 1,7-bis(guanyl)heptane from in vitro reaction mixtures of hepsulfam and calf thymus DNA. We have isolated bis-(7-formamidopyrimidyldeoxyguanosinyl)-heptane from an enzymatic digest of DNA treated with hepsulfam. Finally, we have found that hepsulfam forms interstrand cross-links at 5'-GXC-3' sites in model oligonucleotides. PMID- 7882359 TI - Effects of thymidylate synthase inhibition on thymidine kinase activity and nucleoside transporter expression. AB - The effects of de novo dTMP inhibition by N-(5-[N-(3,4-dihydro-2-methyl-4 oxoquinazolin-6-ylmethyl)-N- methylamino]-2- thenoyl)-L-glutamic acid (D1694) or N6-[4-(morpholinosulfonyl)benz]-N6-diaminobenz[cd]indole glucuronate (AG-331) on clonogenic survival, thymidylate synthase (TS) and thymidine kinase (TK) activity, and expression of S-(p-nitrobenzyl)-6-thioinosine-sensitive nucleoside transporter (NT) sites were addressed in the human bladder cancer cell line, MGH U1. These two TS inhibitors are structurally diverse. D1694 is a folate-based TS inhibitor, whereas AG-331 is a novel agent that inhibits the cofactor binding site of the enzyme. They also differ with respect to their cytotoxic effects in this cell line; D1694 cytotoxic 50% inhibitory concentration (IC50) and IC90 were 6.0 and 9.0 nM, respectively and IC50 and IC90 for TS inhibition were 2.5 and 4.8 nM, respectively. In contrast, AG-331 cytotoxic IC50 could not be achieved even at concentrations of up to 20 microM for 24-h exposures, and IC50 and IC90 for TS inhibition were 0.7 and 3.0 microM, respectively. Similar effects for D1694 and AG-331 were observed in their modulation of TK activity and NT expression. 5 (SAENTA-x8)-Fluorescein, a highly modified form of adenosine incorporating a fluorescein molecule which binds with a 1:1 stoichiometry to S-(p-nitrobenzyl)-6 thioinosine-sensitive NT sites, was used to investigate the expression of NT following exposure of cells to D1694 and AG-331. TK activity was addressed by the metabolism of [3H]thymidine to [3H]TMP by cellular extracted protein and by an alternative flow cytometric method using a modified form of thymidine incorporating a fluorescent molecule, dansyl-5-amino-2-deoxyuridine. Results obtained by both methods were comparable. At concentrations of 5 and 10 nM, D1694 increased TK activity 2.3-4.5-fold and NT expression 34-39-fold. AG-331, at concentrations of 5 and 10 microM, increased TK activity 1.8-2.5-fold and NT expression 22-31-fold, respectively. These data suggest that TK activity and NT expression have a common regulatory mechanism which is sensitive to endogenous dTTP pools and that the salvage pathway is a complex system of kinases coordinated with transport of nucleosides. PMID- 7882360 TI - Differences in inhibition of chromosome separation and G2 arrest by DNA topoisomerase II inhibitors merbarone and VM-26. AB - Merbarone, a novel DNA topoisomerase II (topo II) inhibitor, differs from teniposide (VM-26) in that it inhibits topo II activities without stabilizing topo II-DNA covalent complexes. Thus, while the cellular effects of VM-26 are the consequences of inhibition of topo II catalytic activities and generation of topo II-mediated DNA damage, those of merbarone may be due to inactivation of topo II catalytic function. To address the issues of mechanisms of cell cycle effects and pharmacological actions of these two topo II inhibitors in mammalian cells, we used synchronized cultures of HeLa cells to study the effects of these drugs on cell cycle processes where topo II is essential (e.g., chromosome separation) or possibly involved (e.g., G2 arrest, DNA replication). We found that both drugs inhibited chromosome separation and cell division without preventing cells from exiting mitosis. Both drugs caused S-phase retardation G2 arrest, and phase specific cytotoxicity in that they are more toxic to S, M, and G2 cells than G0/G1 cells. However, merbarone produced the above effects in convergent dosages that were within one to five times its 90% inhibitory cytotoxic concentration, whereas the concentrations of VM-26 to cause quantitatively similar effects were quite divergent. VM-26 is 50-100-fold more efficient in causing G2 arrest than in inhibiting chromosome separation. Furthermore, at concentrations showing similar levels of S-phase suppression, VM-26 caused significant DNA breaks, while merbarone had no such effect. Our data suggest that the effects of merbarone and VM-26 during mitosis are most likely due to inhibition of topo II function. We conclude that while G2 arrest by VM-26 is related to topo II-mediated DNA damage and its sequelae, G2 arrest by merbarone likely results from different mechanisms. PMID- 7882361 TI - Response of colon cancer cell lines to the introduction of APC, a colon-specific tumor suppressor gene. AB - The APC gene, mutations in which are responsible for the inherited colon cancer syndrome adenomatous polyposis coli (APC), is described as a tumor suppressor gene. A full-length, wild-type APC gene was introduced by transfection into three human colon carcinoma cell lines, each characterized for mutations at loci involved in colon tumor formation. The response of each cell line to the introduction of APC differed with the genotype of the cell line. Some of the cell clones derived from these transfections displayed altered morphologies; some showed suppression of tumorigenicity based on growth in soft agar and tumor formation in nude mice. One cell line, SW480, could not be stably transfected with the APC gene. These results provide the first direct evidence that the APC gene can alter the transformation properties of colon carcinoma cells. PMID- 7882362 TI - 1,25-Dihydroxyvitamin D3 enhances the expression of transforming growth factor beta 1 and its latent form binding protein in cultured breast carcinoma cells. AB - Transforming growth factor beta s (TGF-beta s) are a family of polypeptide growth factors that regulate cellular growth, phenotype, and differentiation. TGF-beta s are synthesized as latent high molecular weight complexes that include the NH2 terminal remnant of the TGF-beta precursor (latency-associated protein) and, frequently, latent TGF-beta binding protein. After activation, TGF-beta s act as local mediators of hormonal responses in target tissues. TGF-beta functions as a negative growth regulator for both breast cancer cells and normal mammary epithelial cells. Vitamin D3 is growth inhibitory for the estrogen receptor negative breast cancer cell line BT-20 and regulates TGF-beta expression in cultured keratinocytes. We studied here the effects of vitamin D3 and its analogues on TGF-beta expression and activity in BT-20 cells. It was found that vitamin D3 enhanced both TGF-beta 1 mRNA and secretion of the protein in a time- and dose-dependent manner. Analyses of the vitamin D3 responses in the presence of cycloheximide or actinomycin D indicated that the TGF-beta 1 mRNA induction was dependent on both protein and RNA synthesis. The amounts of latent TGF-beta binding protein were also increased in the conditioned medium but not in the pericellular matrix of vitamin D3-treated cultures. The amounts of active TGF beta were enhanced in vitamin D3-treated cultures as well, suggesting autocrine or paracrine functions for the secreted growth factor. Some analogues of vitamin D3 (EB 1089, MC 903, and KH 1060) that are known to be potent inhibitors of breast cancer cell growth both in vitro and in vivo had similar or more pronounced inducing effects on TGF-beta 1 mRNA levels. The present results indicate that vitamin D3 and its analogues are potent inducers of both active and latent forms of TGF-beta 1 in BT-20 breast carcinoma cells and provide evidence for coordinated regulation of latent TGF-beta binding protein and TGF-beta 1. PMID- 7882363 TI - Instability of microsatellites in human gliomas. AB - We have analyzed DNA obtained from 10 glioblastomas multiforme and 6 astrocytomas for microsatellite instability, using 17 different microsatellite loci dispersed over 7 different chromosomes. Six of 16 gliomas showed 1 or more microsatellite alterations in tumor DNA as compared to constitutional DNA. We observed microsatellite instability resulting in allelic shifts in 5 of 10 glioblastomas multiforme but not in any of the astrocytomas. Loss of an allele was observed in 3 glioblastomas multiforme. An imbalance in the intensity of alleles was noticed in 1 astrocytoma and in 1 glioblastoma multiforme. In 1 glioblastoma multiforme, an extra allele was present at two distinct loci. Overall, 5.3% of microsatellite analyses showed an abnormality. We conclude that microsatellite instability is present at a low grade in glioblastomas multiforme but to a lesser extent in astrocytomas. Genomic instability in human gliomas, therefore, should not be regarded as a mechanism for tumor initiation but as an evolution in tumor progression. PMID- 7882364 TI - Characterization of hprt splicing mutations induced by the ultimate carcinogenic metabolite of benzo[a]pyrene in Chinese hamster V-79 cells. AB - The molecular basis for putative aberrant splicing of hypoxanthine (guanine) phosphoribosyltransferase (hprt) pre-mRNA in Chinese hamster V-79 cells was determined for 75 independent (+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10 tetrahydrobenzo[a]-pyrene [(+)-BPDE]-induced and 6 spontaneous 8-azaguanine resistant mutant clones that had exon deletions in their hprt cDNA. Genomic DNA fragments corresponding to the missing exons and their flanking intron regions were amplified by PCR and sequenced. The results indicated that each of these mutants generated a normal-sized PCR product and resulted from aberrant splicing. For (+)-BPDE-induced aberrant splicing mutants, 81% (61 of 75 clones) had base substitution mutations, 5% (4 of 75 clones) had a single base deletion, and 13% (10 of 75 clones) lacked a detectable mutation in the skipped exon, its flanking intron sequences, or in the upstream donor site of the preceding intron. All mutations at a splice donor site resulted in skipping of the entire upstream neighboring exon, whereas alterations at a splice acceptor site caused skipping of the downstream neighboring exon or activation of a cryptic acceptor site in the downstream exon. Fifty-nine % of the splicing mutants had a mutation occurring at the splice site consensus sequence in the intron, and 28% of the splicing mutants had mutations within exon sequences. Among 21 aberrant splicing mutant clones with a mutation inside an exon sequence, seven were in exon 2, two were in exon 3, and twelve were in exon 4. Evidence is presented that a stemloop structure sequesters the splice donor site of exon 2 in pre-mRNA and plays a role in exon 2 skipping. Mutant clones with mutations stabilizing the proposed stemloop structure inhibited the use of the normal exon 2 splice site which resulted in exon 2 skipping in the hprt mRNA. These mutant clones expressed a mixed population of mRNAs, and both normal-sized and truncated mRNA were formed. Similar to our earlier finding that treatment of V-79 cells with (+)-BPDE resulted in a dose-dependent mutation profile within the coding region of the hprt gene, we also observed the presence of dose-dependence in the profile of (+) BPDE-induced base substitutions in aberrant splicing mutants. As the dose of (+) BPDE was decreased, the proportion of base substitution mutations at AT base pairs that affected RNA splicing was increased. PMID- 7882365 TI - Inhibition of proliferation by L-myc antisense DNA for the translational initiation site in human small cell lung cancer. AB - We evaluated the antiproliferative effect of L-myc antisense DNA in NCI-H209, a human small cell lung cancer (SCLC) cell line overexpressing the L-myc gene. The synthetic DNA used in the present study was oligodeoxynucleoside phosphorothioate, which showed rapid incorporation into NCI-H209 cells and localized mainly in the cell nucleus and weakly in the cytoplasm. The exposure of this cell line to L-myc antisense DNA covering the translational initiation site of L-myc proteins inhibited the cell proliferation in a dose-dependent sequence specific manner. Furthermore, the growth inhibition by this antisense DNA was correlated with the level of L-myc expression in three SCLC cell lines, NCI-H209, NCI-H510, and NCI-H82. In Western blot analysis, expression of the L-myc proteins was down-regulated in the antisense-treated cells compared with control-treated cells in NCI-H209. Together with unique characteristics of the L-myc gene, including: (a) a frequently amplified and overexpressed state in SCLC; and (b) very restricted and low-level expression in human adult tissues, the present data indicate that L-myc is a good candidate for the target gene for antisense DNA therapy based on molecular biological diagnosis in SCLC. PMID- 7882366 TI - Four cytogenetic subgroups can be identified in endometrial polyps. AB - We have cytogenetically investigated a total of 33 simple benign endometrial polyps, 7 of which have been reported previously. Clonal chromosome rearrangements are found in 19 of 33 lesions (57%). Three major cytogenetically abnormal subgroups can be distinguished: (a) those with rearrangements in the 6p21-p22 region; (b) those with rearrangements of the 12q13-15 region; (c) those with rearrangements of the 7q22 region. A normal karyotype is found in a fourth subgroup. Recombinations of the 6p21-22 region with 2q35 and 10q22, as well as rearrangements of 7q22, have not been described before. It can be concluded that endometrial polyps, like several other types of benign mesenchymal tumors, present several cytogenetically different subgroups despite a seemingly identical clinical and morphological appearance. It is mandatory, therefore, to look for a common denominator of these tumors at the molecular level. PMID- 7882367 TI - Cytogenetic and flow cytometry DNA analysis of regional heterogeneity in a low grade human glioma. AB - This study combined flow cytometry with standard cytogenetic analysis of first division cells to evaluate regional heterogeneity in 38 spatially mapped regions of a low grade human oligoastrocytoma. Histologically, the tumor was relatively homogeneous. In contrast, flow cytometry and cytogenetic analyses identified variable percentages of near-diploid (ND; 35 to 57 chromosomes/metaphase) and near-tetraploid (81-103 chromosomes/metaphase) populations. The largest proportion of cells in the ND population was 46,XY with normal Giemsa bands; however, four karyotypically unrelated ND clones also were identified. The development of these clonal populations centered around a region in which more than 50% of the cells contained nonclonal abnormalities and which demonstrated more histological pleomorphism than any other region. The frequency of the nonclonal karyotypes suggested that this region was genetically unstable. Three of the clonal ND populations resided in small, spatially discreet areas of the tumor. The largest and the most widely distributed clonal population, 47,XY,+7, underwent further evolution to give rise to seven additional sidelines. This investigation demonstrates that low grade gliomas have areas of genetic instability capable of generating mutant cells with the capacity to proliferate and to form cellular foci. As a result, multiple, spatially distinct clonal populations can exist in low grade gliomas, some of which are capable of further cytogenetic evolution and clonal expansion, resulting in tumor progression. PMID- 7882368 TI - Macrophage colony-stimulating factor mediates invasion of ovarian cancer cells through urokinase. AB - The macrophage colony-stimulating factor (CSF-1) is best known as a hematopoietic cytokine important to macrophage activation. Recently, the importance of CSF-1 and its receptor (encoded by the c-fms proto-oncogene) in epithelial ovarian cancer has also been recognized, with overexpression of CSF-1 denoting poor prognosis in ovarian cancer patients. During macrophage activation, CSF-1 promotes urokinase-type plasminogen activator (uPA) activity; in macrophages and in malignant cells of lung, breast, colon, and prostatic origin, uPA activity is strongly correlated with the ability to invade and, in the malignant cells, to metastasize. While there is clear evidence of CSF-1 and uPA expression in primary and metastatic ovarian cancer, the significance of their expression to invasion of these cells has not been explored. We find that all of our ovarian cancer cell lines which we have studied co-express CSF-1 and uPA transcripts and protein. Urokinase expression in these ovarian cancer cell lines correlates with the degree of tumorigenicity in nude mice, with the most virulent tumor resulting from Hey cells, a strong expressor of uPA. We studied the invasion of these primary and established ovarian cancer cells through a Matrigel (reconstituted basement membrane matrix) barrier. The ability of ovarian cancer cells to invade is strongly correlated with endogenous CSF-1 expression (Pearson's correlation, r = 0.91; P = 0.01). A total of 0.90 +/- 0.16% of Bix3 cells (very weak expressor of CSF-1) invaded through the barrier, in contrast to 6.95 +/- 0.75% of Hey cells (strong CSF-1 expressor) and 10.44 +/- 2.33% of Bixler cells (the strongest CSF-1 expressor). We studied the ability of two of the cell lines to invade human laminin and type IV collagen (Bix3, a weak invader of Matrigel, and Hey, a strong invader), to determine (a) whether our results on a Matrigel matrix may represent a relevant model for invasion in humans and (b) whether there is a potential confounding effect from the cytokines and proteases in Matrigel. On this human simple matrix, we confirm that Bix3 is a weakly invasive cell line (0.33 +/- 0.04% invasion) which contrasted to the strongly invasive Hey cell line (8.51 +/- 0.47%). Treatment of Bix3 cells with exogenous CSF-1 stimulates percentage of invasion by 2-fold and results in a similar increase in the level of uPA transcripts and cellular associated uPA antigen. Furthermore, cell surface-bound uPA increased from 74% in the absence of CSF-1 to 100% (fully saturated) in the presence of CSF-1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7882369 TI - A human erythrocyte-derived growth-promoting factor with a wide target cell spectrum: identification as catalase. AB - We have reported previously that a factor with a molecular weight of 53,000 under SDS-polyacrylamide gel electrophoresis purified from human erythrocyte extracts promoted the growth of a wide variety of cell types from different species, including T cells, B cells, myeloid leukemia cells, melanoma cells, and mastocytoma cells, as well as normal and transformed fibroblast cells. In the present study, amino acid sequence analysis revealed that this factor has homology with human catalase. The purified factor exhibited catalase activity. Catalases derived from human erythrocytes, bovine liver, Aspergillus niger, and recombinant rat liver catalase are all able to promote the growth of cells. Antibody against human catalase absorbed both the growth-promoting activity and the enzyme activity of the purified factor. In addition, treatment of the factor with an irreversible enzyme inhibitor, aminotriazole, resulted in abrogation of both the growth-promoting activity and enzyme activity. These results indicate that the growth-promoting factor is catalase, and its activity is associated with the decomposition of hydrogen peroxide. PMID- 7882370 TI - PML nuclear bodies are general targets for inflammation and cell proliferation. AB - Acute promyelocytic leukemia is associated with a t(15;17) translocation that generates a fusion product between PML and the retinoic acid receptor alpha. Recently, PML was shown to concentrate within subnuclear domains, referred to as nuclear bodies, that are disorganized in acute promyelocytic leukemia cells. This observation provided the first evidence that alteration of a nuclear structure may play a role in human pathogenesis. In an attempt to clarify the role of PML and, more generally, of the associated nuclear bodies, we used immunohistochemistry to explore the expression of PML in normal, inflammatory, and neoplastic human tissues. With the exception of endothelial cells and macrophages that contain a high amount of PML protein, a weak speckled labeling pattern was observed in the nucleus of all cell types analyzed. By contrast to normal tissues, the level of PML expression was considerably enhanced in inflammatory tissues, predominantly around the mononuclear cell infiltrate, as well as during either normal or pathological proliferative states, in particular in tumoral pathology. Surprisingly, in most hepatocellular carcinoma, a cytoplasmic delocalization of PML was observed. Finally, the number of PML nuclear bodies increased up to twice their normal value as quiescent cultured cells were stimulated to grow upon serum addition. Altogether these results strongly suggest that the PML-associated nuclear bodies are implicated both in the inflammatory process and in cell growth control. PMID- 7882371 TI - Anterior encephaloceles: a report of 30 cases. AB - Thirty cases of anterior encephalocele treated in our centre over an 18-year period (from 1973 to 1990) are presented. At the time of surgery over 60% of the patients were under the age of 2 years, and 40% were aged under 1 year. Only one child was over 10 years of age. Twenty-six patients had the fronto-ethmoidal type of defect, while two each had frontonasal- and naso-orbital-type lesions. Twenty five children had varying degrees of hypertelorism. Four had an enlarged head and four microcephaly. In 26 patients one-stage repair of the encephalocele and reconstruction of the orbits was undertaken. A ventriculoperitoneal shunt was performed prior to definitive surgery in three patients with gross hydrocephalus. There was no postoperative mortality. Six patients had postoperative CSF rhinorrhoea, three of them requiring a lumboperitoneal shunt. This study highlights the role of one-stage repair of this defect. PMID- 7882372 TI - Abnormalities of water metabolism in children and adolescents following craniotomy for a brain tumor. AB - We conducted a retrospective analysis of the cases of 122 children operated on for various brain tumors, to determine the incidence and natural history of postoperative diabetes insipidus (DI), and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Abnormalities of water homeostasis were observed in 15 patients (12%). DI, with or without SIADH, was observed in 10 patients (8%), while SIADH alone was seen in five (4%). DI was permanent in five subjects (50%), whereas SIADH resolved completely in all affected individuals. Parenteral desmopressin (dDAVP) was an effective mode of therapy in the postoperative period. The effect did not correlate with a dosage strictly based on body weight. PMID- 7882373 TI - Paediatric head trauma: influence of age and sex. I. Epidemiology. AB - A consecutive unselected series of 1812 children (up to 15 years old) admitted for head injuries over a period of 8.5 years was studied. The cases were divided up according to five categories of pathology: benign injury, extradural haematoma, subdural haematoma, open brain laceration and brain contusion in a broad sense. All cases of benign injury were from the Geneva area (57000 children) and 52% of the cases of severe injury were referred from other places. To these 1812 cases were added those of 23 children who died before admission recorded by the police. In the Geneva area the mortality was 6.8/100,000 per year. Patients were divided into three age groups: I (0-3 years), II (3-9 years), and III (9-15 years); group I was further subdivided into subgroups I a (0-1 year) and I b (1-3 years). The incidence of each type of accident was calculated for each age group, separately for girls and boys. Each type of pathology was correlated, sex by sex and for different ages, with the type of accident. Overall, two boys were injured for each girl. Road accidents were responsible for 15% of head injuries in group I girls, 17% in group I boys, 43% in group II girls, 45% in group II boys, 50% in group III boys and 61% in group III girls. They were responsible for 94% of all deaths and 85% of deaths of hospitalized patients. Falling was the most frequent cause of injury. Benign injuries were more frequent in group I. Only 1 of 25 patients with extradural haematomas died, and there were only 8 patients with subdural haematomas, 4 in subgroup I a (babies aged less than 1 year). PMID- 7882374 TI - Paediatric head trauma: influence of age and sex. II. Biomechanical and anatomo clinical correlations. AB - A consecutive, unselected series of 1812 cases of head trauma in children less than 15 years of age and admitted hospital over a period of 8.5 years was studied. Data concerning the grade of energy involved, the ages of the victims, the types of pathologies caused and the clinical features noted were collected and statistically analysed. Babies and toddlers (0-3 years) were shown to sustain rather low-energy trauma and suffer more skull fractures, more subdural haematomas and more benign injuries. They lost consciousness less frequently and were less frequently in coma than the other children. By contrast, they had more frequent signs of lateralization, and early seizures were much more frequent in babies than in other children. Young children (3-9 years) had rather higher energy accidents, frequently lost consciousness, were more frequently in coma and have more frequently had a free interval associated with the development of brain swelling. They did not suffer subdural effusion or contrecoup lesions. Schoolchildren (9-15 years) were statistically more or less like young adults: the clinical sequences of trauma were more severe than in the other children, mortality was a little bit higher, the risk of extradural haematoma was higher, and they rarely suffered subdural haematomas or contrecoup lesions. Traffic accidents, with higher energy involved, were more severe. PMID- 7882375 TI - Time-related patterns of ventricular shunt failure. AB - Proximal obstruction is reported to be the most common cause of ventriculoperitoneal (VP) shunt failure, suggesting that imperfect ventricular catheter placement and inadequate valve mechanisms are major causes. This study retrospectively examined patterns of shunt failure in 128 consecutive patients with symptoms of shunt malfunction over a 2-year period. Factors analyzed included site of failure, time from shunt placement or last revision to failure, age of patient at time of failure, infections, and primary etiology of the hydrocephalus. One hundred of these patients required revisions; 14 revisions were due to infections. In this series there was a higher incidence of distal (43%) than of proximal (35%) failure. The difference was not statistically significant when the overall series was considered; however, when factoring time to failure as a variable, marked differences were noted regardless of the underlying cause of hydrocephalus or the age of the patient. Of the 49 patients needing a shunt revision or replacement within 2 years of the previous operation, 50% had proximal malfunction, 14% distal, and 10% had malfunctions attributable directly to the valve itself. Also, 12 of the 14 infections occurred during this time interval. In sharp contrast, of the 51 patients having shunt failure from 2 to more than 12 years after the previous procedure, 72% had distal malfunction, 21% proximal, and only 6% had a faulty valve or infection. This difference between time to failure for proximal versus distal failures was statistically significant (P < 0.00001 for both Student's t-test and non-parametric Mann Whitney U-test).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882376 TI - Brain stem dermoid cyst. PMID- 7882377 TI - Clival chordoma in early childhood without bone involvement. AB - Intracranial chordomas are rare in childhood. Only 15 cases have been reported in children less than 6 years old. Bone destruction and calcification have been stated to be characteristics of this tumor. We present the case of a 5-year-old boy with clival chordoma without bone involvement. PMID- 7882378 TI - Ventriculosubgaleal shunt in the management of recurrent ventriculoperitoneal shunt infection. AB - The use of a ventriculosubgaleal shunt for temporary treatment of hydrocephalus in a child with multiple recurrent shunt infections related to eczema in the neck is described. Further shunt infection was avoided, the eczema cleared, and a permanent ventriculoperitoneal shunt was inserted successfully after 2 months. PMID- 7882379 TI - The induction of bacillus-Calmette-Guerin-activated killer cells requires the presence of monocytes and T-helper type-1 cells. AB - Previously we have described the induction of MHC-unrestricted killer cells against bladder tumour cells by bacillus Calmette-Guerin (BCG), termed BCG activated killer (BAK) cells. In the present paper we deal with the accessory cell requirement for the activation of BAK cells. We show that monocytes are required for activating BAK cells, since no cytotoxicity can be induced in the absence of monocytes. Therefore, these phagocytes may represent the first step during the activation cascade of BAK cells. Furthermore, the presence of CD4+ T cells was essential for generating BAK cells: depleting peripheral blood mononuclear cells of CD4+ cells prior to stimulation with BCG abolished the cytotoxicity against bladder tumour cells. Experiments with monoclonal antibodies (mAb) neutralizing the activity of either interleukin-2 (IL-2) or interferon gamma (IFN gamma) underlined the importance of these cytokines: both mAb blocked the induction of BAK cells. Since both cytokines are related to the so-called Th1 pattern of T cells, we consider the second step of the generation of BAK cells as follows: monocytes presenting antigens of BCG trigger Th1-like cells in a preferred manner. These Th1-like T cells secrete IL-2 and IFN gamma and, thus, activate the BAK effector cells. Since CD4+ cells are dominant in the cells infiltrating the bladder wall after intravesical instillation of BCG in vivo, we postulate an important role for the Th1 subpopulation. We further postulate that the occurrence of macrophages in this infiltrate seems to be significant in the maintenance of the relapse-free state of the patient. PMID- 7882380 TI - Anti-CD30 immunotoxins with native and recombinant dianthin 30. AB - Immunotoxins were prepared with a Ber-H2 (anti-CD30) monoclonal antibody and native or recombinant dianthin 30, a ribosome-inactivating protein from Dianthus caryophyllus (carnation). Both immunotoxins selectively inhibited protein synthesis by CD30+ cell lines D430B (lymphoblastoid, infected with Epstein-Barr virus), L428 and L540 (both from Hodgkin's lymphoma). IC50 values (concentrations, as dianthin, causing 50% inhibition) ranged from 324 pM to 479 pM (immunotoxin with native dianthin 30) or from 45 pM to 182 pM (immunotoxin with recombinant dianthin 30). The effect of either immunotoxin on protein synthesis by the CD30+ cell line K562 (from a chronic myeloid leukaemia) was not different from that of free dianthin (IC50 higher than nM). PMID- 7882381 TI - Complete response of metastatic renal cell carcinoma to low-dose interferon-gamma treatment. AB - The course of metastatic renal cell carcinoma may be positively influenced by immunotherapeutic agents. We report a case of renal cell carcinoma showing a complete response to once-weekly low-dose s. c. interferon-gamma (IFN gamma) treatment in multiple metastatic sites (lung, chest wall, abdomen, vertebral body), but concomitantly developing a solitary brain metastasis. High initial interleukin-6 (IL-6) levels returned to normal during IFN treatment suggesting that IFN gamma may have interrupted an autocrine IL-6/IL-6-receptor loop of the tumor cells. The duration of complete remission in the extracerebral sites is now 46+ months. IFN gamma may be less active beyond the blood/brain barrier. PMID- 7882382 TI - Production of urinary tumour necrosis factors and soluble tumour necrosis factor receptors in bladder cancer patients after bacillus Calmette-Guerin immunotherapy. AB - Intravesical immunotherapy for bladder cancer is the most effective form of tumour immunotherapy. Following repeated instillations of bacillus Calmette Guerin (BCG) organisms into the bladder large quantities of several cytokines are detected in the urine. These cytokines include interleukins IL-1 beta, IL-2, IL 4, IL-6, IL-8, IL-10, tumour necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) and also soluble intercellular adhesion molecule ICAM-1. In the work reported here we simultaneously quantified urinary levels of TNF alpha, TNF beta, TNF receptor I and TNF receptor II by enzyme-linked immunosorbent assay (ELISA) techniques and compared this with bioactive levels of TNF. This was undertaken with a limited number of patients throughout a course of six instillations of immunotherapy. Sequential instillations of BCG induced secretion of TNF alpha and TNF beta into urine. These cytokines were not always secreted simultaneously, perhaps suggesting differential regulation of their synthesis. Maximal concentrations of TNF alpha were 675 pg/ml and TNF beta 47 pg/ml. High levels of both species of soluble TNF receptor were readily identified in urine. Maximal levels of sTNF-RI were 6200 pg/ml (range from 0) and for sTNF-RII 7800 pg/ml (range from 0). Contrasting with earlier published observations concerning cytokine levels, the concentration of soluble receptor did not increase with repeated instillation. In apparent contrast with the ELISA data, very low levels of bioactive TNF were identified by the L929 bioassay (maximum concentration 1 U/ml) despite the elevated concentration of immunoreactive TNF. The large concentrations of soluble TNF receptor in patients' urine samples could account for the apparently low bioactivity as determined by the L929 cytotoxicity assay. The precise nature of the role of TNF in BCG immunotherapy remains undetermined; however, it is thought that proinflammatory cytokines are in part responsible for the clinical efficacy of this therapeutic approach. Whether other cytokines are antogonised by soluble binding proteins remains to be determined. Furthermore, whether TNF is bioactive in the bladder wall and only neutralised in the urine also requires investigation. PMID- 7882383 TI - Specific tumor memory induced by polyethylene-glycol-modified interleukin-2 requires both helper and cytotoxic T cells. AB - Local polyethylene-glycol (PEG)-modified interleukin-2 (IL-2) immunotherapy of the guinea pig Line 10 (L10) tumor was previously demonstrated to evoke long lasting systemic immunity after cure of the tumor and metastases. T cells, most likely the helper T cell subpopulation, were demonstrated to be crucial to the antitumor effects. Here we show that systemic immunity is induced within 7 days after the start of PEG-IL-2 therapy, indicating a rapid systemic priming of L10 specific T cells. No in vitro cytotoxic activity was detected in cell suspensions obtained from the primary tumor site, the regional lymph node or the spleen when isolated during (days 21 and 28) intratumoral treatment with 200,000 IU PEG-IL-2. These data confirm our earlier results obtained with 60,000 IU PEG-IL-2. Moreover, no cytolytic activity was observed in the chromium-release assay after in vitro restimulation with irradiated tumor cells. Specific L10 immunity can be transferred using spleen cell suspensions. Depletion of such a suspension of helper T cells resulted in rejection of the primary tumor in two out of four animals, but all the guinea pigs developed lymph node metastases. Removal of the cytotoxic/suppressor phenotype caused rejection of the dermal tumor in four of eight guinea pigs, but the capacity to prevent lymph node metastases was retained in all animals. Thus, depletion of either subtype reduces, but does not abrogate, the capacity to transfer L10 immunity with spleen cells. In conclusion, our data suggest that tumor cell killing through direct T cell cytotoxicity is not the main mode of action in PEG-IL-2-induced L10 tumor regression. PEG-IL-2 therapy induces early systemic immunity, resulting in rejection of a distant tumor, and the transfer of this immunity depends mainly on the presence of helper T cells, although cytotoxic T cells may also play a role. PMID- 7882384 TI - Expression of monoclonal-antibody-defined antigens in fractions isolated from human breast carcinomas and patients' serum. AB - The aim of this study was to examine tissue from patients with breast carcinoma or benign breast disease for the presence of monoclonal-antibody-defined antigens, including the MUC1 mucin and carcinoembryonic antigen CEA. The tests were performed by sodium dodecyl sulphate/polyacrylamide gel electrophoretic separation of proteins, electrophoretic transfer to nitrocellulose membranes and immunostaining with the monoclonal antibodies. Some of the antigens identified are known to circulate at high levels in some but not necessarily all, breast carcinoma patients. Serum from a panel of ten breast cancer patients was subjected to a fractionation procedure designed to release antigen from immune complexes, and again these samples were analysed for the presence of monoclonal antibody-defined antigens. A high frequency of positive reactions was detected by the anti-MUC1 monoclonal antibody C595 with both breast carcinoma subcellular membrane fractions as well as antigen fractions eluted from circulating immune complexes. No reactions were observed with equivalent materials from benign breast disease samples. The findings illustrate the variability in antigen expression between breast tumours. The data also indicate that a proportion of patients respond to their tumour by the production of antibodies that recognise the MUC1 antigen in their circulation. PMID- 7882385 TI - Inhibition of proliferation and induction of apoptosis by abrogation of heat shock protein (HSP) 70 expression in tumor cells. AB - Tumor cells often express elevated levels of heat-shock protein (HSP) 70. The present study was designed to investigate the role of HSP70 in the proliferation and survival of tumor cells in the human system. When Molt-4 and other tumor cells were treated in vitro with HSP70 antisense oligomer, they displayed propidium-iodide-stained condensed nuclei (intact or fragmented). A ladder-like pattern of DNA fragments was observed with HSP70 antisense-oligomer-treated tumor cells in agrose gel electrophoresis, which was consistent with internucleosomal DNA fragmentation. Flow cytometry analysis revealed the hypodiploid DNA peak of propidium-iodide-stained nuclei in the antisense-oligomer-treated cells. The apoptosis induced by HSP antisense oligomer was dose- and time-dependent. The antisense oligomer induced apoptosis mainly in tumor cells at G1 and S phase, resulting in an inhibition of cell proliferation. HSP70 antisense oligomer caused DNA-sequence-specific inhibition of HSP70 expression, which preceded apparent apoptosis. These results indicate that HSP70 antisense treatment inhibits the expression of HSP70, which in turn inhibits cell proliferation and induces apoptosis in tumor cells and suggest that HSP70 is required for tumor cells to proliferate and survive under normal condition. PMID- 7882386 TI - Neurotransmitter suppression of the in vitro generation of a cytotoxic T lymphocyte response against the syngeneic MOPC-315 plasmacytoma. AB - We have previously shown that, as a consequence of low-dose melphalan (L phenylalanine mustard (L-PAM) therapy, the hitherto immunosuppressed spleen cells from BALB/c mice bearing a large MOPC-315 tumor (in contrast to spleen cells from normal mice) acquire the ability to generate a greatly enhanced anti-MOPC-315 cytotoxic T lymphocyte (CTL) response upon in vitro stimulation with MOPC-315 tumor cells. Here we show that the catecholamines norepinephrine, epinephrine, and isoproterenol suppressed the in vitro generation of anti-MOPC-315 cytotoxicity by spleen cells from mice that had just completed the eradication of a large MOPC-315 tumor following low-dose L-PAM therapy (L-PAM TuB spleen cells), as well as by spleen cells from normal mice. In contrast to the marked suppression obtained with catecholamines, the cholinergic agonist carbachol had no effect on the in vitro generation of splenic anti-MOPC-315 cytotoxicity. The inhibitory effect of the catecholamines was "mimicked" by the membrane penetrating analog of cAMP, dibutyryl-cAMP, and by cholera toxin at concentrations that stimulate the endogenous production of cAMP. The beta adrenergic receptor antagonist propranolol did not block norepinephrine-induced inhibition of the generation of anti-MOPC-315 cytotoxicity by either normal or L PAM TuB spleen cells. Since the curative effectiveness of low-dose L-PAM therapy for MOPC-315 tumor bearers requires the participation of CD8+ T cells that exploit a CTL response in tumor eradication, it is conceivable that norepinephrine may reduce the therapeutic outcome of low-dose chemotherapy by inhibiting the acquisition of CTL activity. PMID- 7882387 TI - Increased tumor cell reactivity and complement-dependent cytotoxicity with mixtures of monoclonal antibodies against different gangliosides. AB - Melanomas and other cancers of neuroectodermal origin express multiple cell surface gangliosides in patterns that vary significantly even within the same tumor type. Monoclonal antibodies (mAb) against four of these gangliosides (GM2, GD2, 9-O-acetyl-GD3 and GD3) were tested alone and in combination on 14 tumor cell lines (7 melanomas, 3 neuroblastomas, 3 sarcomas and 1 astrocytoma) using flow cytometry and complement-dependent cytotoxicity (CDC) assays. Increased tumor cell recognition and CDC resulting from the combination of three or four mAb were found in 14/14 tested cell lines, and this was most striking when each mAb was used at suboptimal concentration. At these concentrations, the average mean fluorescence intensity of the 14 cell lines with individual mAb was between 3.0 and 6.8 and increased to 10.8 and 18.8 with the three- and four-mAb mixtures. The average percentage CDC-specific release with individual mAb was 2.0%-8.3%, and 12.3% and 16.6% with the three- and four-mAb combinations. The number of cell lines showing significant mean fluorescence intensity and CDC increased from 2 8/14 with single mAb to 13-14/14 with the mixtures of three or four mAb. Our experimental results support the rationale for active immunization with a polyvalent ganglioside vaccine or passive therapy with a combination of mAb to different gangliosides in patients with tumors of neuroectodermal origin. In addition, our studies have demonstrated that 9-O-acetyl-GD3 is a surprisingly effective target for immune attack, although it is a minor constituent of these cells. PMID- 7882389 TI - [Late ventricular potentials and acute ischemia: study during percutaneous transluminal coronary angioplasty]. AB - In order to assess if acute ischemia induces ventricular late potentials (VLP), we have studied 35 patients during coronary angioplasty (PTCA), 15 (Group A) with previous myocardial infarction, 20 (Group B) without. VLP detection was performed by standard technique (in the time domain, with Simson algorithm, on 200 beats, using a 25 Hz filter) before, during and 24 hours after PTCA. This procedure was performed on: anterior descending artery (19 cases), circumflex artery (9 cases), right coronary artery (11 cases); four patients had PTCA on two vessels; in Group A patients, PTCA was performed in vessels related to the previous myocardial infarction. VLP were defined as present when at least two of three standard criteria of positivity were detected (QRSD > 115 ms, RMS40 < 25 microV, LPD > 32 ms). In all patients also left ventricular ejection fraction, end diastolic pressure, regional kinesis and amount of myocardium at risk (as measured by the "Duke University jeopardy score") had been assessed. Furthermore, the total and mean inflation time and the degree of induced acute ischemia were also considered. The following results were obtained: no patient had VLP at basal conditions, during PTCA in all patients of both groups we observed a significant prolongation of QRSD but only Group A patients developed VLP, in 56% of cases versus none of Group B. This event was transient: in fact, 24 hours after the procedure VLP were no more present. The two groups did not differ as regards to the values of all the other anatomic and functional above mentioned parameters. Probably the acute ischemia cannot evocate VLP by itself, but this "trigger" needs also a particular substrate with anatomical and functional abnormalities due to a previous myocardial infarction. Further investigations and long follow up studies are requested to assess if these data could account for the presence of ventricular tachyarrhythmias in patients with acute coronary ischemia and previous myocardial infarction. PMID- 7882388 TI - Characterization of tumor-necrosis-factor-gene-transduced tumor-infiltrating lymphocytes from ascitic fluid of cancer patients: analysis of cytolytic activity, growth rate, adhesion molecule expression and cytokine production. AB - We characterized tumor-infiltrating lymphocytes (TIL) from ascites of patients with ovarian or pancreatic cancer in which the human tumor necrosis factor (TNF) gene was successfully transduced with retrovirus vector. The TNF-gene-transduced TIL (TNF-TIL) from these patients showed a higher level of TNF production and higher cytotoxic activity against K562 and Daudi cells than did neomycin phosphotransferase-gene-transduced TIL (neo-TIL). Of these TIL preparations, only that from pancreatic cancer was further characterized since it was collected in a relatively large amount. In spite of the fact that the autologous tumor cells showed resistance to soluble TNF, the TNF-TIL clearly demonstrated enhanced cytotoxicity against them as compared with neo-TIL. The enhanced cytotoxicity was ascribed to autocrine effects of secreted TNF on TIL, which included augmentation of adhesion molecule (CD2 and CD11a) and interleukin-2 receptor expression, and elevation of production of interferon gamma, lymphotoxin and granulocyte/macrophage-colony-stimulating factor and its paracrine effect on target cells to facilitate them to be more susceptible to TIL. PMID- 7882390 TI - [Ambulatory monitoring of left ventricular function in patients with ischemic heart disease: effects of coronary revascularization]. AB - The aim of this study was to assess the efficacy of coronary artery bypass using an ambulatory radionuclide monitoring system of left ventricular function (VEST) during daily activities in patients with previous myocardial infarction and coronary artery disease. Ten patients with previous myocardial infarction, clinical evidence of residual angina and angiocardiographically proven coronary artery disease of at least two epicardial vessels were studied by VEST 8 +/- 2 days before and 15 +/- 3 days after surgical myocardial revascularization. VEST allows to monitor both left ventricular function and 2 ECG leads. During the radionuclide monitoring (at least 60 min) all patients underwent handgrip test (compression of a dynamometer for 2 min at the 75% of maximal capacity), a mental stress (arithmetic operation consisting in subtracting 17 from 17,000 for 4 min), walking (140 yards) and climbing stairs (8 flights). No significant changes in left ventricular function during mental stress and handgrip both before and after the surgical procedure were observed. In the preoperative evaluation, walking induced a significantly increase in heart rate from rest to peak exercise (73 +/- 13 versus 79 +/- 11 b/min, respectively; p < 0.01). After coronary artery bypass, heart rate (rest: 92 +/- 18 b/min, effort: 98 +/- 19 b/min; p < 0.01), ejection fraction (rest: 47 +/- 8%, effort: 53 +/- 10%; p < 0.01), cardiac output (rest: 43 +/- 8 edv/min, effort: 51 +/- 11 edv/min, p < 0.01), and stroke volume (rest: 47 +/- 9%, effort: 53 +/- 9%; p < 0.01) increased at maximal effort compared to the control conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882391 TI - [Anterior ST segment depression in acute inferior myocardial infarct: significance of its reproducibility during early ergometric test]. AB - The significance of anterior ST segment depression (V1-V4) at the time of acute inferior myocardial infarction and exercise-induced anterior ST segment depression were studied in 30 patients. All patients carried out: two-dimensional echocardiography in the acute phase of myocardial infarction (Echo 1) and at predischarge (Echo 2); symptom-limited exercise test; coronary arteriography. According to ST segment changes, patients were divided into Group A (n = 15) with exercise-induced anterior ST segment depression and Group B (n = 15) with no ST segment depression during exercise. Group A showed a lower work physical capacity than Group B (6.8 +/- 3 METS and 9 +/- 2 METS, respectively). The wall motion index in Group A was 0.26 +/- 0.14 in the Echo 1 and 0.22 +/- 0.18 in the Echo 2 showing an improvement in wall motion abnormality; in Group B the same index was 0.35 +/- 0.19 in the Echo 1 and 0.34 +/- 0.18 in the Echo 2. Group A patients had a higher prevalence of multivessel disease compared with Group B patients and the right coronary artery was always involved. In conclusion, in inferior myocardial infarction the anterior ST segment depression, both in the acute phase and during the predischarge exercise test, reflects more extensive coronary disease and jeopardized myocardium. PMID- 7882392 TI - [Evaluation of cardiac risk in patients undergoing major vascular surgery. Usefulness and limitations of transesophageal atrial pacing]. AB - Patients undergoing vascular surgery are at high risk of developing cardiac events in the perioperative period. The aim of the study was the evaluation of the predictive accuracy of transesophageal atrial pacing (TAP) in identifying patients at higher risk of developing major cardiac events (cardiac death, acute myocardial infarction, unstable angina, heart failure and sustained ventricular tachyarrhythmias). We studied 96 consecutive patients, 80 males and 16 females, median age 63, requiring arterial surgery (aortofemoral or aortoiliac bypass and thromboendoarterectomy, abdominal aneurysm resection and extracranial carotid thromboendoaterectomy). TAP was performed without cardioactive drugs in all patients, but one. After surgery CK and CKMB serial assessment and ECG recording were performed daily until the seventh postoperative day. Preoperatively all patients were admitted to the Intensive Care Unit and submitted to haemodynamic monitoring with Swan-Ganz catheter at least for 72 hours. Three patients did not undergo surgery because of severe ST depression during TAP. Thus, 93 patients (96.8% of the series) were the subject of this report. In the postoperative period only two events (2.1% of the patients) were recorded, one relapsing acute myocardial infarction and one ventricular fibrillation, both in patients with negative TAP. No death occurred. Our study shows a very low prevalence of major cardiac events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882393 TI - The diagnostic significance of real sinus node automaticity depression in symptomatic sinus bradycardia. AB - Atrial overdrive pacing was performed, before and after autonomic blockade, in 42 consecutive patients (32 males and 10 females, mean age 46 +/- 11 years) with symptomatic sinus bradycardia. Patients were divided into two groups: Group I, 23 patients (mean age 43 +/- 8 years) with normal intrinsic heart rate (IHR) and normal intrinsic corrected sinus node recovery time (intrinsic CSNRT < 425 ms) and Group II, 19 patients (mean age 49 +/- 13 years) with abnormal intrinsic sinus node automaticity identified after autonomic blockade by abnormal IHR and/or by abnormal intrinsic CSNRT (> 425 ms). In addition to sinus cycle length, IHR, maximal CSNRT and sinoatrial conduction time (SACT) the real sinus node automaticity depression (SAD) was also evaluated, calculated after autonomic blockade (intrinsic CSNRT-SACT). Not all patients with an abnormal IHR showed abnormally prolonged CSNRT and not all patients with normal IHR had normal CSNRT. Among Group I (normal IHR) in 19 patients the real SAD was < 300 ms, while among Group II in 8 of 11 patients showing abnormal IHR the real SAD was > 300 ms. The abnormal value of SAD (> 300 ms) observed not only in patients with abnormal IHR and/or abnormally prolonged intrinsic CSNRT but also in several patients with normal IHR, increases the sensitivity of testing and may allow to detect even latent organic sinus node dysfunction. In conclusion, a synopsis of IHR, intrinsic CSNRT and intrinsic SACT with real SAD may be useful to estimate more accurately the degree of the impairment of intrinsic sinus node automaticity helping to differentiate the organic sinus node dysfunction from the autonomic one. PMID- 7882394 TI - [Indications for heart catheterization in heart valve diseases in 1994]. PMID- 7882395 TI - [Left ventricular myocardial hypertrophy: role of proto-oncogenes and ACE inhibition]. PMID- 7882396 TI - [Contribution of magnetic resonance imaging to the diagnosis of 2 cases of cardiomyopathy]. AB - Two cases of cardiomyopathy were studied by echocardiography, endomyocardial biopsy carried out during cardiac catheterization and magnetic resonance imaging. In accordance with echocardiogram, magnetic resonance imaging showed global thickening of the free and septal wall in the first case and apical thickening in the second case. The alteration of the tissue component described by magnetic resonance imaging is in agreement with the histologic description of endomyocardial biopsy. Magnetic resonance imaging is a useful method for the diagnosis of cardiomyopathy. PMID- 7882397 TI - Infrainguinal directional atherectomy: long-term follow-up and comparison with percutaneous transluminal angioplasty. AB - PURPOSE: To assess the long-term results of directional atherectomy (DA) for femoropopliteal artery atherosclerotic lesions and to compare the results to those previously reported for percutaneous transluminal balloon angioplasty (PTA). MATERIALS AND METHODS: Eight-four percutaneous DA procedures performed on 75 patients between July 1988 and August 1992 were retrospectively reviewed and evaluated for technical and initial clinical success. Long-term patency was assessed with a combination of ankle-brachial index measurements and angiography. RESULTS: Initial technical success was achieved in 77 of 84 procedures (92%). Follow-up of 72 patients was obtained, including 74 of the 84 (88%) DA procedures with a mean follow-up of 17.4 months (range 1-48 months). Primary patency was 78% at 1 year and 57% at 2 years. Patients with diabetes, complete luminal occlusion, or limb salvage situations had significantly lower patency. CONCLUSIONS: Femoropopliteal artery DA can be performed safely with a high technical and initial clinical success. Long-term patency is improved when compared with published series for PTA. With this improvement in mind, DA may have a place in the treatment of focal infrainguinal stenoses. PMID- 7882399 TI - Comparison of efficacy in crossing femoropopliteal artery occlusions with movable core and hydrophilic guidewires. AB - PURPOSE: Compare the recanalization rate of femoropopliteal occlusions between movable core wire guide (MG) and hydrophilic guidewire (HG). METHODS: Conventional PTA technique was used, followed by enclosed thrombolysis. The MG was used for all patients in the first 2 years, the HG in the following 2 years. Baseline characteristics were similar for the two groups of patients. RESULTS: Recanalization of 124 femoropopliteal occlusions was attempted. Technical success was achieved with the MG in 45 of 59 procedures; 42 procedures were clinically successful. Using the HG, technical success was achieved in 35 of 65 procedures; clinical success was achieved in 35 of 65 procedures; clinical success was achieved in 29 cases (p < 0.0048). At 1-year follow-up, 32 extremities improved after treatment with MG and 22 extremities after treatment with HG (p < 0.035). CONCLUSION: The results suggest that the MG should be the first choice in recanalization of femoropopliteal occlusions. PMID- 7882398 TI - Percutaneous transluminal atherectomy of the superficial femoral and popliteal arteries: long-term results in 48 patients. AB - PURPOSE: Evaluate retrospectively the long-term primary patency of directional atherectomy (DA) in the femoropopliteal arteries. MATERIALS AND METHODS: DA was used alone in 59 patients (47%) or in combination with predilatation to allow passage of the device (43%) or after thrombolysis (10%) to treat 127 (93%) excentric atherosclerotic stenoses and nine (7%) occlusions of the femoropopliteal arteries. Forty-eight patients were followed by telephone interview, scheduled outpatient visits, color-flow Doppler evaluation, and angiography for 1-36 months (mean 16.9 months). RESULTS: Technical success (reduction of the stenosis or occlusion to less than 30% luminal diameter) was achieved in 110 lesions (80.3%) during 48 procedures in 37 patients. Mean luminal diameter was increased 54% with a concomitant increase in mean ankle/brachial indices of 0.33. According to Kaplan-Meier survival curves, patency at 12 and 24 months was 88% and 75%, respectively. When patients who retained patency but developed restenosis were excluded, the probability of patency at 12, 24, and 36 months was 76%, 58%, and 32%, respectively. Major and minor complications occurred in 15 (21.4%) procedures each for a total complication rate of 42.8%. CONCLUSION: Based on our results, DA is an effective method for percutaneous treatment of atherosclerotic disease involving the femoropopliteal arteries. It has similar patency but a relatively high complication rate compared with PTA. PMID- 7882400 TI - Bilateral subclavian steal syndrome: treatment with percutaneous transluminal angioplasty and stent placement. AB - A 66-year-old man presented with bilateral subclavian steal syndrome (SSS) due to proximal subclavian artery occlusions. He was treated by percutaneous transluminal balloon angioplasty (PTA) and stent implantation in the left subclavian artery and by PTA alone in the right subclavian artery. We could demonstrate that interventional treatment of symptomatic bilateral SSS is possible. If PTA alone is insufficient, stent implantation should be considered. PMID- 7882401 TI - Thrombolysis and angioplasty for acute lower limb ischemia in Buerger's disease. AB - Acute lower limb ischemia secondary to Buerger's disease in a young patient responded to thrombolysis and subsequent popliteal and anterior artery angioplasty. The value of angioplasty in non-limb-threatening ischemia in Buerger's disease has not been established but this case illustrates a role for thrombolysis and angioplasty in acute ischemia. PMID- 7882402 TI - Postlaminectomy arteriovenous fistula masked by stenosis of the inferior vena cava. AB - Discovery of a postlumbosacral discectomy fistula between the right iliac artery and vein was obscured by an associated severe stricture of the infrarenal inferior vena cava in a 49-year-old man. During venous stenting for treatment of peripheral edema, the fistula was suspected because of faint pulsatile right iliac vein flow and increased O2 saturation of the venous blood. The suspicion was confirmed on subsequent iliac arteriography. Surgical closure of the fistula with arterial interposition grafting was then performed. The patient improved substantially. PMID- 7882403 TI - Percutaneous internal fistulization of a lung abscess after incomplete external drainage. AB - Internal drainage was performed with expandable metallic stents in a 79-year-old male with lung abscess secondary to bronchogenic carcinoma. Initial external drainage was prolonged, and internalization of drainage allowed removal of the external drainage catheter. Connection of abscess cavity to obstructed bronchus was created after passing a steerable guidewire percutaneously through the abscess into the bronchus. This new type of internal drainage technique may be applicable to patients with prolonged standard percutaneous external drainage of lung abscesses. PMID- 7882404 TI - A new coaxial needle system, hepatic artery targeting wire, and biplane fluoroscopy to increase safety and efficacy of TIPS. AB - To improve safety and efficacy of the transjugular intrahepatic portosystemic shunt (TIPS) procedure, we introduced a new, thin-needle (21-gauge long PTC needle) puncture technique using biplane fluoroscopy and targeting of a guidewire tip in the right hepatic artery. After puncture of the right portal vein, a 0.016 inch guidewire was inserted into the portal vein, followed by a 4 Fr dilator. The 4 Fr dilator allowed introduction of a 0.035-inch working guidewire. We successfully performed TIPS in seven patients with postnecrotic cirrhosis using this technique and encountered no technical difficulties or complications. PMID- 7882405 TI - Percutaneous retrieval of a central venous catheter sutured to the wall of the inferior vena cava. AB - A central venous catheter was sutured to the wall of the inferior vena cava in a 20-year-old male undergoing retroperitoneal lymphadenectomy for malignant testicular germ cell tumor. We succeeded in retrieving the catheter percutaneously, using a combination of loop-snare wire and myocardial biopsy forceps. PMID- 7882406 TI - Re: A new curved peel-away sheath for central venous catheter placement: technical note. PMID- 7882407 TI - Mitral valvulplasty for mitral stenosis during pregnancy: a case study. PMID- 7882408 TI - A survey of clinical trial coordinators: factors influencing job satisfaction and turnover. PMID- 7882409 TI - Comparison of symptoms, functional ability, and health perception of elderly patients with coronary artery disease managed with three different treatment modalities. PMID- 7882410 TI - An exploration of perceived barriers to cardiovascular risk reduction. PMID- 7882411 TI - Risk factors for coronary heart disease in African-American women. PMID- 7882412 TI - Haematologic features of the human immunodeficiency virus (HIV) infection in Black children in Harare. AB - Forty six Black Zimbabwean children aged between three months and seven years who were admitted into Parirenyatwa Central Hospital with serologically positive and symptomatic HIV infection were investigated for their haematologic profiles. Tests done included full blood counts, manual white cell differential counts, coagulation screening tests and bone marrow aspiration in clinically indicated cases. Anaemia was found in 84 pc, leucocytosis in 60 pc and thrombocytopaenia in 30 pc of the cases. In contrast to reports in adults leucopaenia or neutropaenia were not seen. Coagulation profiles were mostly normal but presumptive diagnosis of circulating coagulation inhibitor was made in one case. Morphological changes suggestive of myeloid dysplasia and in particular dysgranulopoiesis were commonly seen. Bone marrow aspirates examined in eight of the children all showed hyper or normal cellularity with adequate and productive megakaryocytes. PMID- 7882413 TI - An investigation of the schistosomiasis transmission status in Harare. AB - A schistosomiasis prevalence and intensity survey was carried out among school children in selected residential suburbs of Harare. Urine and stool specimens were collected for determination of schistosomiasis infection from 2,552 children aged between five and 15 years. A total of 351 (13.7 pc) school children were found to be infected with Schistosoma haematobium while 172 (6.7 pc) pupils were found to be positive for S. mansoni. The arithmetic mean egg count (AMEC) for S. haematobium was 16 while that for S. mansoni was 7.6 figures much lower than those found among school children in rural areas. Malacological studies revealed the presence of infected intermediate hosts of schistosomiasis in some water bodies in and around Harare signifying the potential for transmission. The factors contributing to this observation are discussed. Prevalence and annual incidence of schistosomiasis was highest among children of high density suburbs on the outskirts of Harare where children had access to unprotected and untreated water usually outside the city boundaries. The lack of recreational facilities in these areas was found to be a major contributing factor towards the transmission of schistosomiasis as children were sometimes forced to use water bodies outside the City of Harare boundaries for such activities. The possible contribution of religious activities is also discussed. PMID- 7882414 TI - Hepatic function tests in children with sickle cell anaemia during vaso occlusive crisis. AB - Thirty children with sickle cell anaemia had their serum alanine aminotransferase, alkaline phosphatase, total protein, albumin and bilirubin, assayed during vaso-occlusive crisis and at recovery. Alanine aminotransferase, alkaline phosphatase and bilirubin levels were significantly higher during crisis than at recovery, (p < 0.005) especially in the young patient. However, the total protein and albumin levels were not significantly different in crisis and at recovery. A transient hepatic functional derangement during vaso-occlusive crisis is a probable explanation for the reported changes. PMID- 7882415 TI - The Zimbabwe External Quality Assessment Scheme (ZEQAS) in clinical chemistry: results of the pilot programme. AB - A pilot programme for assessing laboratory performance in clinical chemistry laboratories in Zimbabwe is described (ZEQAS). Twenty four laboratories providing patient care services participated. Eight lyphilised bovine sera were distributed over one year. Consensus values and the spread of interlaboratory agreement were calculated for each of 12 analytes and compared with results previously obtained in a large mature national EQA scheme in the UK (UK NEQAS). For all analytes except phosphate, the mean consensus value obtained in ZEQAS was between 94 and 108 pc of the UK target, although the spread of results in ZEQAS was generally two to threefold greater for individual analytes than in UK NEQAS. It is concluded the ZEQAS consensus values for the analytes surveyed provide a valid target against which individual laboratory performance can be assessed. The wide spread of results from individual laboratories suggests there is considerable scope for improving interlaboratory agreement. This is being addressed by the continuing programme, with increased interaction and production of local specimens. PMID- 7882416 TI - Complete rectal prolapse in adults: a Tanzanian experience. AB - This is a retrospective report of nine patients with complete rectal prolapse managed by the authors at the Muhimbili Medical Centre, Dar es Salaam between 1990 and 1993. The average age of patients was 36 years and eight of the patients were males. Six of the patients presented as emergency admissions of whom three had irreducibility and required perineal proctosigmoidectomy. This was the procedure of choice for irreducible complete rectal prolapse. PMID- 7882417 TI - Delayed diagnosis of retinoblastoma. AB - The initial clinical presentation of retinoblastoma can mimic other non-malignant conditions. This may cause a delay in accurate diagnosis with fatal consequences. Two cases are presented in which the initial impression of panophthalmitis and congenital cataract, respectively, led to delay in diagnosis. The need for early clinical diagnosis bearing in mind the masquerading tendency of retinoblastoma is emphasized. Treatment modalities readily available in our environment are highlighted. PMID- 7882418 TI - Bilateral fracture of the femoral neck as a direct result of electrocution shock. PMID- 7882419 TI - The gastroscope, labour intensive family planning and incentives. PMID- 7882420 TI - Hydatidiform mole. AB - This article critically reviews the current understanding of the origin of hydatidiform mole. The pathogenesis, clinical presentation and diagnosis is discussed. Suction curettage and close patient follow up reduces the mortality and morbidity of the patients with this disease. PMID- 7882421 TI - Saccharomyces cerevisiae YDR1, which encodes a member of the ATP-binding cassette (ABC) superfamily, is required for multidrug resistance. AB - A multidrug resistance gene, YDR1, of Saccharomyces cerevisiae, which encodes a 170-kDa protein of a member of the ABC superfamily, was identified. Disruption of YDR1 resulted in hypersensitivity to cycloheximide, cerulenin, compactin, staurosporine and fluphenazine, indicating that YDR1 is an important determinant of cross resistance to apparently-unrelated drugs. The Ydr1 protein bears the highest similarity to the S. cerevisiae Snq2 protein required for resistance to the mutagen 4-NQO. The drug-specificity analysis of YDR1 and SNQ2 by gene disruption, and its phenotypic suppression by the overexpressed genes, revealed overlapping, yet distinct, specificities. YDR1 was responsible for cycloheximide, cerulenin and compactin resistance, whereas, SNQ2 was responsible for 4-NQO resistance. The two genes had overlapping specificities toward staurosporine and fluphenazine. The transcription of YDR1 and SNQ2 was induced by various drugs, both relevant and irrelevant to the resistance caused by the gene, suggesting that drug specificity can be mainly attributed to the functional difference of the putative transporters. The transcription of these genes was also increased by heat shock. The yeast drug-resistance system provides a novel model for mammalian multidrug resistance. PMID- 7882422 TI - The byp1-3 allele of the Saccharomyces cerevisiae GGS1/TPS1 gene and its multi copy suppressor tRNA(GLN) (CAG): Ggs1/Tps1 protein levels restraining growth on fermentable sugars and trehalose accumulation. AB - Byp1-3 is an amber nonsense allele of the Saccharomyces cerevisiae GGS1/TPS1 gene which encodes the small subunit of the trehalose synthase complex. Mutations in this gene confer an inability to grow on glucose or fructose but the phenotype of byp1-3 mutants is leaky in a strain-dependent manner. Overexpression of the isolated byp1-3 allele suppressed the growth defect of a ggs1/tps1 delta mutant. Expression of an in-vitro-generated mutant allele of GGS1/TPS1 that lacks all the coding sequences downstream from the byp1-3 mutation led to the production of a shortened protein that did not complement the ggs1/tps1 delta mutant. We have isolated, as an allele-specific multi-copy suppressor of the growth defect of the byp1-3 mutant on fructose, the gene for tRNA(GLN) (CAG). Thus the leaky phenotype of byp1-3 mutants is due to a low level of read through of the internal nonsense codon by tRNA(GLN) (CAG). Using overexpression of the isolated byp1-3 allele, as well as of the tRNA(GLN) (CAG) gene, we were able to demonstrate that as little as about 10% of the normal Ggs1/Tps1 protein level is sufficient for slow growth on fructose. We also show a correlation between the level of Ggs1/Tps1, the ability to accumulate trehalose in stationary phase and the ability to grow on fermentable sugars. Sequence analysis of the cloned tRNA(GLN) (CAG) gene showed that it is located 700 bp upstream of URA10. However, we found considerable differences to the reported sequence of URA10, in particular in the non-coding region. PMID- 7882423 TI - Nonrandomly-associated forward mutation and mitotic recombination yield yeast diploids homozygous for recessive mutations. AB - We have employed the analysis of spontaneous forward mutations that confer the ability to utilize L-alpha-aminoadipate as a nitrogen source (alpha-Aa+) to discern the events that contribute to mitotic segregation of spontaneous recessive mutations by diploid cells. alpha-Aa- diploid cells yield alpha-Aa+ mutants at a rate of 7.8 +/- 3.6 x 10(-9). As in haploid strains, approximately 97% (30/31) of alpha-Aa+ mutants are spontaneous lys2-x recessive mutations. alpha-Aa+ mutants of diploid cells reflect mostly the fate of LYS2/lys2-x heterozygotes that arise by mutation within LYS2/LYS2 populations at a rate of 1.2 +/- 0.4 x 10(-6). Mitotic recombination occurs in nonrandom association with forward mutation of LYS2 at a rate of 1.3 +/- 0.6 x 10(-3). This mitotic recombination rate is tenfold higher than that of a control LYS2/lys2-1 diploid. Mitotic segregation within LYS2/lys2-x subpopulations yields primarily lys2 x/lys2-x diploids and a minority of lys2-x aneuploids. Fifteen percent of lys2 x/lys2-x diploids appear to have arisen by gene conversion of LYS2 to lys2-x; 85% of lys2-x/lys2-x diploids appear to have arisen by mitotic recombination in the CENII-LYS2 interval. lys2-1/lys2-1 mitotic segregants of a control LYS2/lys2-1 diploid consist similarity of 18% of lys2-1/lys2-1 diploids that appear to have arisen by gene conversion of LYS2 to lys2-1 and 82% of lys2-1/lys2-1 diploids that appear to have arisen by mitotic recombination in the CENII-LYS2 interval.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882424 TI - The yeast protein Mrs6p, a homologue of the rabGDI and human choroideraemia proteins, affects cytoplasmic and mitochondrial functions. AB - MRS6 is a newly-identified gene in the yeast Saccharomyces cerevisiae. Its product Mrs6p shows significant homology to the mammalian GDP dissociation inhibitor (GDI) of Rab/Ypt-type small G proteins and to the human choroideraemia protein (CHM), the component A of Rab-specific GGTase II. The interaction of Mrs6p with G proteins is indicated by our observation that the MRS6 gene suppresses the effect of a temperature-sensitive ypt1 mutation. Disruption of the MRS6 gene is lethal to haploid yeast cells. This is consistent with the notion that Mrs6p is interacting with Rab/Ypt-type small G proteins, which are known to have essential functions in vesicular transport. Unexpectedly, the MRS6 gene product also affects mitochondrial functions as revealed by the facts that high copy numbers of MRS6 (1) suppress the pet- phenotype of mrs2-1 mutant strains and (2) cause a weak pet- phenotype in wild-type strains. We conclude from these results that the MRS6 gene product has a vital function in connection with Rab/Ypt-type proteins in the cytoplasm and, in addition, affects mitochondrial functions. PMID- 7882425 TI - Biochemical and genetical studies of NADP-specific glutamate dehydrogenase in the fission yeast Schizosaccharomyces pombe. AB - The initial velocity, pH and temperature optima, and Km values of Schizosaccharomyces pombe NADP-glutamate dehydrogenase (NADP-GDH:EC 1.4.1.4) have been determined. NADP-GDH was found to be specific for the substrates used in the reaction mixtures. NADP-GDH activity showed a sigmoidal response to changes in alpha-ketoglutarate concentrations, following Hill kinetics with a coefficient nH = 2. A two-fold and a three-fold increase in activity was found in extracts of cells grown on a medium containing cytosine or histidine as a sole nitrogen source, respectively, relative to the activity found in cells grown on other sole nitrogen sources including ammonium, adenine, arginine, aspartate, asparagine, glutamate, glutamine, leucine, lysine, proline, uridine and urea. Five NADP-GDH defective mutants were isolated on the basis of no growth on ammonium plus allantoin as sole nitrogen sources. The mutants also failed to grow on allantoin alone but, in contrast, they were phenotypically indistinguishable from the wild type growing on solid minimal medium with ammonium. Additionally, the mutants were found to grow as wild-type on minimal medium with alanine, arginine, asparagine, aspartate, glutamate, glutamine, leucine, ornithine and proline in the absence or presence of allantoin. In liquid minimal medium with ammonium as sole nitrogen source they had a slower growth than the wild-type. Normal growth was observed in cells grown on alanine, arginine, asparagine, aspartate, glutamate, glutamine, leucine, ornithine and proline. The mutants had undetectable levels of NADP-GDH activity, but retained wild-type levels of NAD GDH, glutame synthase (GOGAT) and glutamine synthetase (GS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882426 TI - Partial nucleotide sequence of a single ribosomal RNA coding region and secondary structure of the large subunit 25 s rRNA of Candida albicans. AB - A rDNA cistron of Candida albicans strain WO-1 was cloned and the ITS1, ITS2, 5.8 s rDNA and 25 s rDNA coding regions sequenced in their entirety. These sequences were compared to those of three related yeast species (Saccharomyces cerevisiae, Saccharomyces carlsbergensis, and Thermomyces lanuginosus), and the 5.8 s rDNA was compared to seven additional 5.8 s rDNAs from organisms ranging in complexity from D. discoideum to H. sapiens. The C. albicans ITS regions are shorter than those of most other eukaryotes. The 25 s and 5.8 s rDNA sequences were folded into a secondary structure model based on comparative methods. In a comparison of regional similarities between the large subunit rDNAs of C. albicans, the three related yeasts and other eukaryotes, it is demonstrated that the additional sequences not present in the E. coli 23 s rDNA are more variable than the regions present in both prokaryotes and eukaryotes. PMID- 7882427 TI - Mutations in the structural gene for cytochrome c result in deficiency of both cytochromes aa3 and c in Neurospora crassa. AB - The cyt-12-12 mutant of Neurospora crassa is characterized by slow growth and a deficiency of spectrophotometrically-detectable cytochromes aa3 and c. Using a sib-selection procedure we have isolated the cyt-12+ allele from a cosmid library of N. crassa genomic DNA. Characterization of the cyt-12+ allele reveals that it encodes the structural gene for cytochrome c. DNA sequence analysis of the cyt-12 12 allele revealed a mutation in the cytochrome c coding sequence that results in replacement of a glycine residue, which is invariant in the cytochrome c of other species, with an aspartic acid. Genetic analysis confirms that cyt-12-12 is allelic with the previously-characterized cyc-1-1 mutant, which was also shown to affect the single locus encoding cytochrome c in N. crassa. We suggest that the amount of functional cytochrome c present in mitochondria influences the level of cytochrome aa3. PMID- 7882428 TI - A kalilo-like linear plasmid in Louisiana field isolates of the pseudohomothallic fungus Neurospora tetrasperma. AB - Two Louisiana strains of Neurospora tetrasperma contain a linear plasmid (LA kalDNA) with a restriction map identical to the Hawaiian Neurospora intermedia senescence plasmid, kalDNA, but with termini 100 nucleotide pairs shorter. One of these strains also bore a circular plasmid similar to the Hawaiian circular plasmid Hanalei-2. One species probably acquired both plasmids from the other by horizontal transfer, at a time sufficiently distant for sequence divergence to take place. Many LA-kalDNA-bearing derivative strains senesced, but this plasmid does not guarantee senescence. Furthermore, LA-kalDNA does not insert into mtDNA. One senescent strain showed no LA-kalDNA. The plasmids are effectively transmitted via the pseudohomothallic sexual cycle. Single mating-type derivatives transmit plasmids maternally. PMID- 7882429 TI - Clustering of multiple transgene integrations in highly-unstable Ascobolus immersus transformants. AB - A large proportion of Ascobolus immersus transformants are highly unstable in crosses: the phenotype conferred by the transgene is not transmitted to the progeny, irrespective of the endogenous or foreign origin of the transgene. They all have integrated multiple transgene copies, clustered at a single chromosomal site or at tightly-linked sites. Clustered non-homologous integrations are always rearranged. Yet they never escape the "methylation induced premeiotically" (MIP) process. This always results in gene silencing, even when the transgene is partially repeated, accounting for the high instability of these transformants. PMID- 7882430 TI - Cointegration of transforming DNAs in Aspergillus nidulans: a model using autonomously-replicating plasmids. AB - Transforming DNAs form cointegrates in Aspergillus nidulans by homologous and non homologous recombination as well as by end-to-end ligation of linear fragments. This process has been studied by means of a model in which the linkage of a marker gene to the origin of autonomous replication AMA1 was selected for. Recombinant plasmids were rescued into Escherichia coli and subjected to restriction mapping and sequence analysis. It was shown that circular DNA molecules recombined predominantly within homologous fragments. Linear DNA fragments integrated into circular plasmids by invasion of their ends into random non-homologous sites, but exhibited some bias in choice of a target sequence. Cointegrates of multiple plasmid copies were often observed. In some of the plasmids analysed, short duplications of the target sequence flanking an inserted linear DNA fragment have been revealed. PMID- 7882431 TI - Genetic diversity in Cronartium quercuum f.sp. fusiforme on loblolly pines in southern U.S. AB - Twelve random amplified polymorphic DNA (RAPD) markers were used to study genetic variability in three populations of Cronartium quercuum f.sp.fusiforme, the causal agent of fusiform rust on pines. Most of the variability (94%) was found within populations while 6% of the total variability was attributable to frequency differences between populations. The frequency of three markers was significantly different between regions of origin on an east-west transect. Three markers were completely absent from one of the populations while present in the others, and one marker was fixed in the western population but polymorphic in the eastern and central populations. However, no significant differences were observed when the western population was omitted from the analysis. The results suggest that C. quercuum f.sp.fusiforme is a highly heterogeneous pathogen with little geographic differentiation and underscores the importance of considering the populations structure of the pathogen in resistance breeding programs. PMID- 7882432 TI - Presence of double-stranded RNA and virus-like particles in Phaffia rhodozyma. AB - Four double-stranded RNA (dsRNA) molecules were isolated from Phaffia rhodozyma UCD 67-385. Their molecular sizes were approximately 4.3, 3.1, 0.9 and 0.75 kilobase pairs (kbp) as determined by agarose-gel electrophoresis and they were designated as L, M, S1 and S2, respectively. By differential centrifugation in sucrose gradients, these dsRNAs copurified with isometric virus-like particles 36 nm in diameter. A cured strain, UV-S2, lacking the S2-dsRNA was obtained from P. rhodozyma UCD 67-385 by ultraviolet (UV) light treatment. UV-S2 strain contains identical virus-like particles to those from the wild-type strain, as determined by electron microscopy, suggesting that the S2-dsRNA was not essential for the expression of mycovirus structural polypeptides. On the other hand, both the UCD 67-385 and UV-S2 strains were able to kill P. rhodozyma UCD 67-383, a strain without dsRNAs. These results suggest that the dsRNA molecules also encode a killer system. Finally, the UV-S2 strain maintains killer ability, which suggests that S2-dsRNA is not involved in the killer phenotype expression. PMID- 7882433 TI - UV hypersensitivity of yeast linear plasmids. AB - The Kluyveromyces linear plasmids pGKL1 and pGKL2, encoding killer activity, were efficiently cured by UV irradiation. This event was investigated in more detail by the use of the terminal protein (TP)-associated cytoplasmic linear plasmids, pJKL1 and pRKL2, with a selectable marker LEU2. This observation was compared with the UV effect on the nuclear plasmids pLS1 (telomere-associated linear form) and YCp121 (centromere-integrated circular form), indicating that the UV hypersensitivity was specific to the cytoplasmic plasmids. Using rad4 and wild type strains of S. cerevisiae, both pJKL1 and the nuclear plasmids were found to respond not only to photoreactivation repair but also to excision repair of UV induced DNA damage. Thus these DNA repair systems were functional for both the nuclear and cytoplasmic plasmids in yeast, and it was suggested that the UV hypersensitivity of cytoplasmic plasmids might have been caused by a defect in other repair systems or in the TP-primed replication. Possibly TP-associated Debaryomyces linear plasmids were also UV hypersensitive. PMID- 7882434 TI - Nucleotide divergence between populations of trembling aspen (Populus tremuloides) estimated with RAPDs. AB - In the present study, a total of 142 trees sampled from five populations of trembling aspen (Populus tremuloides Michx.) in Alberta was analyzed by the polymerase chain reaction (PCR) with five random oligonucleotide primers. Null allele frequencies of 28 putative RAPD loci were estimated using the given departure from Hardy-Weinberg equilibrium (F1S) previously estimated with isozyme markers for the same population. Nucleotide divergence between populations was then estimated in a fashion similar to restriction-fragment data, but considering the dominance of the RAPDs. The average of nucleotide divergence between populations was in the order of 0.0005 and nucleotide divergence were found to be highly correlated with geographic distance. The results suggest that isolation by distance may be an important factor in the genetic differentiation of trembling aspen. PMID- 7882436 TI - [Thyroid carcinoma]. PMID- 7882437 TI - [Morphologic imaging of thyroid carcinoma]. AB - Ultrasonography (US) is the choice morphological imaging modality in the study of thyroid carcinomas. The present technological evolution (high frequency probes, development of Colour-Doppler) allows the detection of small non-palpable nodules, being able to define, in a high percentage of cases, features pointing to the malignant character of a thyroid mass, although the definite assessment of malignancy (invasion of adjacent structures, metastatic cervical nodes) is quite rare. From a diagnostic viewpoint US is required to identify nodules with suspect features, to be submitted to fine needle aspiration biopsy. Moreover, US plays a basic role in the staging--at the cervical level--of carcinomas as well as in the post-operative follow-up. The other imaging modalities (Computed Tomography, Magnetic Resonance Imaging) play a limited role in both staging and post operative follow-up. PMID- 7882435 TI - [Epidemiology and risk factors in thyroid carcinoma]. AB - Thyroid carcinoma represents less than 2% cancers although there is an increasing incidence, mainly of the papillary variety, due in part to improved diagnostic procedures. In contrast there is a remarkably higher prevalence of occult foci in detailed autopsy studies (up to 34%) suggesting the possibility of a spontaneous regression for most of them. Only 1-2% of latent tumours grow larger and become clinically important through environmental, genetic and cellular factors (two mutational event model by Knudson). Each single histological subgroup has different influencing factors: X ray exposure, iodide diet intake, coexisting (autoimmune and non) thyroid disease such as thyroiditis, Graves' disease, goitre, dyshormonogenesis, heredity and altered cellular oncogenes have been considered. Of a series of 715 thyroid cancers operated on between 1967 and 1992 we analyze sex ratio, mean age, radiation exposure, coexisting thyroid disease, familial occurrence. PMID- 7882438 TI - [Papillary carcinoma of the thyroid: nosological aspects, prognostic factors and principles of therapy]. AB - Papillary carcinoma of thyroid, has not, until now, been considered prognostically and therapeutically clear, because it is not free from problematic questions regarding prognosis and treatment, though it has been studied for a long time. The Authors analyse this pathology under actual learning conditions, with reference to the nosologic, prognostic and therapeutic aspects. PMID- 7882439 TI - [Follicular carcinoma and Hurthle cell tumor of the thyroid]. AB - In this paper we present the current therapeutical strategies for follicular carcinoma (10-15% of all thyroid tumours) which is more common in areas of endemic goitre, and is classified according to histology into encapsulated and angioinvasive (more aggressive). The treatment of choice is total thyroidectomy, eventually associated with functional latero-cervical lymphadenectomy. Distant metastases can be treated by surgery if single and resectable, or by radiometabolic therapy in the other cases. Hurthle cell (oxyphilic) tumour, also called oncocytoma, has an unpredictable biological behaviour, even after histological examination. During the eighties the preferred treatment was total thyroidectomy, but currently many authors favour a less aggressive approach, especially with lesions considered "benign" according to the common histological parameters. We too apply an individualised strategy of treatment; follow-up must be very thorough in order to detect early any recurrence. PMID- 7882440 TI - [Medullary carcinoma of the thyroid gland]. AB - The Authors, after introducing the epidemiology and physiopathology of medullary thyroid carcinoma, compare the most recent diagnostic methods and therapeutic strategies. They highlight recent progress in genetics, in diagnosis and therapy and in the role of labelled radiopharmaceuticals in diagnosis, post-operative therapy and follow-up. PMID- 7882441 TI - [Thyroid cancer: anatomy and pathologic histology]. AB - Current pathological classifications of thyroid carcinoma only partially reflect the radical changes in our knowledge of these tumors, due to a large series of clinicopathological studies carried out over the past few years. Based on a critical review of this growing body of information concerning malignant thyroid neoplasms, a working formulation for clinical usage is proposed. This scheme has been adopted to classify 1339 consecutive cases of thyroid carcinoma observed at the Pathology Institute of the University of Florence between June 1966 and December 1993. The clinical implications of newer classification systems with regard to diagnosis, treatment and outcome of thyroid carcinoma are also discussed. PMID- 7882442 TI - [Role of markers in the diagnosis and follow-up of thyroid carcinomas]. AB - Serum thyroglobulin measurement is specified for, the follow-up of patients with treated differentiated thyroid cancer. The thyroglobulin measurement is not good as a screening test of thyroid carcinoma. Serum calcitonin is considered a specific, reliable, easily measurable and repeatable marker of medullary carcinoma, both sporadic and hereditary. This measurement can be used for the follow-up of already diagnosed and treated patients as well as for the screening of medullary carcinoma in patients with thyroid nodules or at risk of MEN 2A and 2B. As there is also evidence of a role for genetic factors in medullary carcinoma when it seems to be sporadic, some recent studies have found genetic markers with the highest diagnostic accuracy. PMID- 7882443 TI - [Scintigraphy in the diagnosis of thyroid carcinoma]. AB - Thyroid scans yield functional information useful in the differential diagnosis of thyroid nodules and are usually performed with TcO4-99m for its favourable physical properties, availability, low cost and good correlation with I123. Cold thyroid nodules are very frequent and generally due to benign diseases. To distinguish the minority representing carcinomas, classes of risk must be selected, according to multiple factors, including external radiation exposure, sex, age, iodine intake and thyroid morphology. These patients will undergo fine needle biopsy which can make the final diagnosis. Its accuracy is often preferred as a first line modality in the diagnostic approach to thyroid nodules. Tumour imaging agents are very useful in the staging and follow-up of thyroid carcinomas, but are rarely needed in the primary diagnosis of the disease. PMID- 7882444 TI - [Radiometabolic therapy in differentiated carcinoma of the thyroid gland]. AB - The use of I131, for metabolic therapy is a procedure that has been used for many years in the treatment of thyroid carcinomas. Nevertheless, there is no agreement in the use of metabolic therapy. In fact there are therapeutic regimens that foresee the use of I131 following total or subtotal thyroidectomy even in the ablation of postsurgical thyroid residuals in patients with favourable pathological stage and there are metabolic therapeutic schemes only for advanced pathological stages. In fact, result of metabolic therapy are very significant in patients with advanced disease, whereas there is little difference between treated and non-treated patients with disease in the favourable stage, even if metabolic therapy allows a more accurate clinical follow-up. Both univariate and multivariate statistical analysis has demonstrated that neoplastic cell iodine uptake, a fundamental mechanism in metabolic therapy, is the most important prognostic factor in patients with advanced disease. The comparison with other types of treatment with respect to logistic organization or simply cost is also in favour of metabolic therapy as this requires a few days of hospitalization, at low cost and with few acute or late side-effects. On the contrary, the need for an adequately protected ward and difficulty in the dosimetry calculation in each metastasis does not favour metabolic therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882445 TI - [Hormonal therapy in differentiated carcinoma of the thyroid gland]. AB - Thyrotropin (TSH) suppression therapy using thyroid hormone plays an important role in the management of patients thyroidectomized for differentiated thyroid cancer. The rationale for TSH suppression is that differentiated thyroid cancer cells have TSH receptors and show increased adenylate cyclase activity following TSH exposure. L-thyroxine is used for long-term therapy. L-triiodothyronine is preferred when suppressive therapy must be discontinued for radioiodine scan, since its shorter half-life allows more rapid increases of TSH levels. The assessment of TSH suppression is still uncertain. The development of second and third TSH assay generations with progressive improvement in sensitivity has made the TRH test unnecessary and has raised the issue of the TSH level indicative of TSH suppression. In clinical practice TSH values below 0.1 mU/L are considered compatible with appropriate TSH suppression. Serum thyroglobulin is a reliable marker of metastatic disease after total surgical and radioiodine ablation of the thyroid gland and it is useful in the surveillance of patients with differentiated thyroid cancer. PMID- 7882446 TI - [Reoperation in differentiated carcinoma of the thyroid gland]. AB - A series of 112 patients reoperated on for differentiated thyroid cancer is analyzed; 60 patients (38 with papillary and 22 with follicular cancer) underwent ex-principio to completion of a non total thyroidectomy and 52 (37 with papillary and 15 with follicular cancer) to repeat surgery for local relapse. At a mean follow-up of 8.7 years, all the 38 patients with papillary cancer reoperated on for completion are alive and disease-free, while of those with follicular cancer 4 are dead, 2 are alive with carcinoma and 16 (72.7%) are disease free. A reoperation for relapse was performed on the thyroid in 11, on the thyroid and nodes in 23 patients (all had initially received partial thyroidectomy), and on nodes alone in 28 patients. At a mean follow-up of 10.2 years, 20 patients (54%) with papillary and 7 (46.6%) with follicular cancer are alive and disease-free, 8 patients with papillary and 1 with follicular cancer are alive with disease and the remainder are dead due to the tumour. Although there is no sure evidence that total thyroidectomy provides higher survival and fewer recurrences, since many factors, predominantly age influence the prognosis, total thyroidectomy is recommended as a minimal procedure to avoid less safe and less radical subsequent reoperation. PMID- 7882447 TI - [Radical interventions in the treatment of thyroid carcinoma]. AB - From 1970 to 1993, 196 patients with thyroid cancer were treated surgically. In 26 (13.2%) an invasion of local and regional structures was observed. Eighteen patients had papillary or follicular carcinoma and 9 anaplastic carcinoma. Tracheal invasion occurred in 11 cases and 7 patients underwent total thyroidectomy, segmental resection of the trachea (1-5 rings) and reanastomosis, associated preoperatively in 2 cases with Nd:YAG laser photocoagulation. Six of thirteen patients with muscle invasion are alive at 2-16 years follow-up; 3 patients with tracheal invasion died in less than 6 months and the others seem to be free of disease 6-14 years after operation. PMID- 7882448 TI - [Complications in thyroid surgery]. AB - Since the first years of the century, the improvement in surgical techniques has drastically reduced the main postoperative complication, profuse bleeding. More experience in thyroidectomy has highlighted other specific problems of the procedure, which has received substantial benefits by the adoption of targeted surgical techniques. The Authors describe the most important topics reported for each complication, on the basis of the latest literature and their own experience, with particular reference to the oncologic surgery of the thyroid. PMID- 7882449 TI - [Intraoperative ultrasonic evaluation of the residual thyroid weight in thyroidectomy in diffuse toxic goiter]. AB - The amount of thyroid tissue to be ablated in unresponsive Basedow disease has mainly, until now, been empirically evaluated. An attempt has been made, using intraoperative ultrasonography, to evaluate the residual tissue. This method allows weight calculation of the thyroid lobe to be ablated through two sonographic measurements of the superior pole axes. This technique provides a precise codification of the intervention and reduces the incidence of recurrence. The results six months after operation prove just two cases of latent hypothyroidism (10%). PMID- 7882450 TI - [Precedents of benign thyroid pathology in carcinoma of the thyroid]. AB - The clinical history of 125 thyroid cancer (99 women and 26 men) operated on between 1985 and 1992 is reviewed. Previous benign thyroid disease is recorded in 52% of all cancers; this was generally goitre or a thyroid nodule, and in few cases hyperthyroidism. Previous disease is observed in 75% of insular, in 68% of follicular, in 51.5% of papillary, in 35% of anaplastic carcinomas. It is supposed that previous thyroid disease is a risk factor in the development of cancer. PMID- 7882451 TI - [Thyroid cancer. General international bibliography]. PMID- 7882452 TI - [Fine needle aspiration biopsy in the diagnosis of thyroid neoplasms]. AB - The clinical value of fine needle aspiration biopsy cytology is discussed with reference to 4514 histologically verified cases. A good sensitivity and specificity, together with high accuracy, make this technique a method of choice in the preoperative diagnosis of thyroid disease. PMID- 7882454 TI - A pilot study of amiodarone with infusional doxorubicin or vinblastine in refractory breast cancer. AB - Increasing evidence suggests that P-glycoprotein (Pgp) expression can mediate drug resistance in refractory breast cancer. We studied 33 patients with refractory breast cancer enrolled in a pilot study of oral amiodarone as a Pgp antagonist given in combination with infusional doxorubicin or vinblastine. Whenever possible, tumors were biopsied and Pgp expression was assayed. Patients received either 60 mg/m2 doxorubicin over 96 h or 8.5 mg/m2 vinblastine over 120 h by continuous intravenous infusion. Beginning with the second cycle of chemotherapy, 600-800 mg amiodarone was given orally each day. Patients who experienced toxicity due to amiodarone but were responding to chemotherapy were placed on quinidine. Partial responses were observed in 9 of 33 patients on study and were sometimes observed after the first cycle of chemotherapy, before amiodarone was given, suggesting that some patients may have responded to treatment because of the infusional schedule. Toxicities were primarily the known side effects of the antineoplastic agents and of amiodarone. The major amiodarone toxicity was gastrointestinal, with nausea, vomiting, anorexia, or diarrhea being noted in 21 patients. Biopsy samples were obtained from 29 patients and in 21 cases, viable tumor tissue was present and the results were interpretable. Of the 21 samples, 9 had Pgp expression as determined by immunohistochemical staining; 12 were considered negative. The presence of Pgp expression was associated with an acceleration of the time to treatment failure. Whereas normal-tissue toxicities related to the combination of a Pgp antagonist with chemotherapy were not observed, amiodarone was associated with too many untoward effects to be utilized as a drug resistance-reversing agent. PMID- 7882453 TI - Characterization of organ-specific immunoliposomes for delivery of 3',5'-O dipalmitoyl-5-fluoro-2'-deoxyuridine in a mouse lung-metastasis model. AB - A previous study has shown that lipophilic prodrugs can be delivered efficiently to normal lung endothelium by incorporation into liposomes covalently conjugated to monoclonal antibody (mAb) 34A against the lung endothelial anticoagulant protein thrombomodulin. In the present study, the potential use of these lung targeted immunoliposomes (34A-liposomes) for delivery of a lipophilic prodrug, 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine (dpFUdR), to the tumor-bearing lung was examined using BALB/c mice bearing experimental lung metastasis induced by i.v. injection of EMT-6 mouse mammary tumor cells. Immunohistochemical examination of the tumor-bearing lung showed specificity of mAb 34A to lung endothelium. Tumor cells appeared to localize just outside of the normal blood vessels and were within a small diffusion distance from the mAb 34A-binding sites. 111In-labeled 34A-liposomes containing monosialoganglioside (GM1) were prepared that included [3H]-dpFUdR at 3.0 mol% in the lipid mixture. In vitro cell binding studies further demonstrated that 34A-liposomes bound specifically to normal mouse lung cells that expressed thrombomodulin but not to EMT-6 cells. Biodistribution study showed efficient and immunospecific accumulation of [3H] dpFUdR incorporated into 34A-liposomes in the lung at a level parallel with that of 111In-labeled 34A-liposomes, indicating that the drug is delivered to the target organ in intact liposomes. Liposomal dpFUdR appeared to be metabolized in the lung to the parent drug FUdR at a rate slower than in the liver and spleen. Furthermore, treatment of lung-metastasis-bearing mice with dpFUdR incorporated into 34A-liposomes on days 1 and 3 after tumor cell injection resulted in a significant increase in the median survival time of treated mice as compared with control mice (%T/C value, 165%). dpFUdR either dispersed in emulsion or incorporated into antibody-free liposomes was ineffective in prolonging the survival of mice. These results indicate the potential effectiveness of organ specific immunoliposomes containing a lipophilic prodrug for the targeted therapy of metastatic tumors. PMID- 7882455 TI - The bioavailability and dose dependency of the deuterated anti-tumour agent 4,6 benzylidene-d1-D-glucose in mice and rats. AB - The benzaldehyde derivative 4,6-benzylidene-D-glucose (BG) induces an inhibition of protein synthesis at otherwise non-toxic doses in cells grown in vitro. To increase the biological effect of BG, the hydrogen in the formyl group was exchanged with deuterium, resulting in 4,6-benzylidene-d1-D-glucose (P-1013). In this study we compared the bioavailability of BG and P-1013, since both intraperitoneal and, especially, oral administration of the drugs would be a great advantage. We also examined whether or not P-1013 displays dose-dependent pharmacokinetics. Pharmacokinetics were studied by analysing plasma samples using reversed-phase high-performance liquid chromatography (HPLC). P-1013 was given at four different doses i.v. (60, 120, 145 and 230 mg/kg) and p.o. (60, 120, 170 and 230 mg/kg) to female Bom:NMRI-nu mice. The bioavailability was more than 50% for all doses. The results also indicate that P-1013 shows linear pharmacokinetics, with no change being observed in the half-life (t1/2) with increasing dose and only a slightly more than proportional increase in the area under the concentration-time curve (AUC) occurring with increasing dose. A doubling in dose resulted in a 2.2-fold increase in the AUC. P-1013 and BG were also given i.v., p.o. and i.p. to female nu/nu-BALB/cABom mice and male Wistar rats. A high degree of bioavailability was found in both species, with 55-100% of the delivered dose being absorbed. Deuteration of BG does not seem to alter its bioavailability, as we found the same bioavailability for P-1013 as for BG. We conclude that the pharmacokinetics of P-1013 does not prevent its use as a cancer treatment drug given orally. PMID- 7882456 TI - Clinical and pharmacology study of chloroquinoxaline sulfonamide given on a weekly schedule. AB - The in vitro human tumor colony-forming assay identified chloroquinoxaline sulfonamide (CQS) as an active agent at human plasma concentrations of > 100 micrograms/ml. In the initial phase I trial of CQS given every 28 days, peak plasma concentrations > 500 micrograms/ml were associated with reversible dose limiting hypoglycemia and occasional cardiac arrhythmias. Therefore, we evaluated whether a weekly schedule of treatment might minimize the drug-associated toxicity while maintaining potential therapeutic concentrations. CQS was given intravenously over 1 h once per week for 4 weeks to 12 patients, beginning at a dose of 2,000 mg/m2. All patients underwent monitoring for cardiac arrhythmias and hypoglycemia. Plasma drug levels were measured following each dose. Mild hypoglycemia was the most common adverse effect. A median nadir plasma glucose concentration of 56 mg/dl was observed at a weekly dose of 2,500 mg/m2. Two patients experienced cardiac dysrhythmia while on study. Continuous electrocardiographic monitoring failed to identify any significant infusion related arrhythmia. The median CQS plasma concentration measured 24 h following a 2,000-mg/m2 dose of CQS was > 100 micrograms/ml, and the cumulative area under the concentration x time curve (AUC) determined at concentrations of > or = 100 micrograms/ml was similar to that observed with the every-28-day schedule. The weekly schedule described herein appears to maximize the plasma AUC with an acceptable margin of safety. The recommended phase II dose and schedule for CQS is 2,000 mg/m2 given once per week. Although severe hypoglycemia is unlikely, glucose monitoring is appropriate for 6 h following CQS administration. PMID- 7882457 TI - Synchronization of cells in the S phase of the cell cycle by 3'-azido-3' deoxythymidine: implications for cell cytotoxicity. AB - The mechanism of synergy between 3'-azido-3'-deoxythymidine (AZT) and anticancer agents was investigated with emphasis on cell-cycle events. Exposure of exponentially growing WiDr human colon carcinoma cells to AZT resulted in synchronization of cells in the S phase of the cell cycle. Following treatment with AZT at 50 or 200 microM, 62% +/- 3% or 82% +/- 4% of the cells were in the S phase as compared with 36% +/- 2% in the control. Bromodeoxyuridine uptake studies revealed that the synchronized cells actively synthesized DNA. At concentrations of up to 200 microM, AZT produced a cytostatic rather than cytotoxic effect as indicated by viability and cell growth measurements. At 200 microM, AZT-induced synchronization was significant (P = < 0.001) after 12 h of drug exposure, reached a maximum at 24 h, and reversed to baseline levels by 72 h even in the continued presence of the drug. This indicates that AZT-induced cytostasis is a transient and reversible effect. The cell-cycle events seen with AZT in WiDr cells were also observed in eight of nine human tumor cell lines tested. Isobologram analysis of WiDr cells preexposed to AZT for 24 h and then exposed to either AZT-5-fluorouracil or AZT-methotrexate for a further 72 h revealed synergy between AZT and the anticancer agents, indicating that AZT induced synchronization may have therapeutic benefits. PMID- 7882458 TI - A phase I study of recombinant human interferon alpha-2b combined with 5 fluorouracil and cisplatin in patients with advanced cancer. AB - To determine the maximum tolerated dose (MTD) of escalating doses of interferon alpha-2b (IFN, Intron A) with 5-fluorouracil (5-FU) and cisplatin (DDP) in patients with advanced cancer, 15 patients were accrued between May 1990 and July 1991. Primary sites were unknown (3), colorectal (3), head and neck (2), lung (2), gynecologic (1), gallbladder (1), sarcoma (1), anal canal (1) and pancreas (1). IFN was given s.c. on days 1-5 and then three times weekly with DDP (75 mg/m2, day 1) and 5-FU [750 mg/m2, days 1-5, continuous infusion (CI) on a 28-day cycle. The first two patients treated at level I (3 x 10(6) U/m2 s.c.) experienced possible neurotoxic deaths [massive cerebrovascular accident (CVA) and metabolic encephalopathy], and patient 3 had a grade 4 toxicity of performance status decline. Analysis of these events led us to exclude the enrollment of patients on i.v. morphine and of those with prior exposure to DDP. This resulted in grade 3 toxicity in terms of nausea, vomiting, fatigue and leukopenia but in no further CNS event. All patients were evaluable for toxicity but only ten were evaluable for response. Only two partial responses were seen, one in a patient with an unknown primary tumour and one in a patient with head and neck cancer. The combination of IFN is possible with 5-FU and DDP. The recommended dose of IFN is 2 x 10(6) U/m2 s.c. in patients with no prior exposure to DDP or i.v. morphine, given together with 5-FU (750 mg/m2, days 1-5, CI) and DDP (75 mg/m2, day 1) on a 28-day cycle. PMID- 7882459 TI - Continuous mitoxantrone infusion in pretreated epithelial ovarian cancer. AB - Mitoxantrone has shown moderate activity in advanced epithelial ovarian cancer following intermittent i.v. administration. Experiments and clinical data suggest that long-term continuous drug infusion may achieve a better therapeutic result with less toxicity. This hypothesis was tested in patients with advanced ovarian cancer who had been pretreated with other agents. Mitoxantrone was infused continuously in 21-day courses beginning every 6 weeks. If severe toxicity did not occur, the infusion rate was increased by 0.1-0.2 mg/m2 per day. The mitoxantrone solution proved to be stable over the 21-day infusion period. For ethical reasons an optimal two-stage design was employed. The trial was interrupted at the end of the first recruitment stage because the target of 3 responses out of 13 patients had not been achieved (only 1 patient had a partial response). Hematologic toxicity was observed in 11 patients, and 2 of them had a catheter occlusion. In conclusion, we found that 21-day of infusion of mitoxantrone apparently has no clinical benefit as compared with bolus administration in patients with advanced ovarian cancer. PMID- 7882460 TI - Synergistic interaction between cisplatin and tamoxifen delays the emergence of cisplatin resistance in head and neck cancer cell lines. AB - The interaction between cisplatin (cDDP) and tamoxifen (TAM) was evaluated in the human head and neck squamous-carcinoma cell lines UM-SCC-10B and UM-SCC-5. Synergy between cDDP and TAM was demonstrated in the UM-SCC-10B cell line. Concordant with the synergistic effect between cDDP and TAM, the rate of development of resistance to cDDP was delayed when selections were performed in the presence of TAM. However, in the UM-SCC-5 cell line, TAM was neither synergistic nor did it delay the development of cDDP resistance. The difference with respect to the synergistic interaction of cDDP with TAM and the effect on the development of cDDP resistance in the UM-SCC-10B and UM-SCC-5 cell lines was not related to any significant difference in the accumulation of the cDDP analog [3H]-cis-dichloro(ethylenediamine)platinum(II) (DEP), drug sensitivity [concentrations inhibiting colony formation by 50% (IC50 values) were 6.5 and 7.2 microM for cDDP and 3.5 and 3.2 microM for TAM, respectively], the number of estrogen and progesterone receptors (negative in both cell lines), the number of antiestrogen binding sites (404 +/- 85 and 353 +/- 24 fmol/mg protein, respectively), or the affinity of TAM for these binding sites (1.7 and 1.5 nM, respectively). Importantly, however, we demonstrated that TAM can delay the emergence of resistance to cDDP in head and neck carcinomas and that this effect is linked to the nature of the interaction between cDDP and TAM. PMID- 7882462 TI - Phase II study of a new vinca alkaloid derivative, S12363, in advanced breast cancer. AB - Vinca alkaloids are widely used in the medical treatment of breast cancer. Our study aimed to evaluate the therapeutic activity of a new vinca alkaloid derivative, S12363 (vinfosiltine), which is 36 and 72 times more cytotoxic in vitro than vincristine and vinblastine, respectively. Because phase I studies did not allow a choice of the best treatment schedule, a randomization was performed between two schedules with the same dose intensity, that is, 0.3 mg/m2 given weekly or 0.6 mg/m2 given every 2 weeks. A total of 16 patients with advanced breast cancer who had failed a first-line treatment without any vinca alkaloid were entered in the study. Additionally, 6 women received the bimonthly regimen as first-line treatment of advanced breast cancer. Altogether, 17 patients received, prior to vinfosiltine, an anthracycline-based regimen given either as adjuvant (n = 4) or as first-line palliative treatment (n = 13). All 22 patients were evaluable for both toxicity and response. Neutropenia was the main toxic event (maximal toxicity per patient) with grade 3 (WHO) toxicity developing in 7/22 patients and grade 4, in 8/22. Other severe toxicities included leukopenia (n = 9), anemia (n = 1), diarrhea (n = 1), constipation (n = 1), and fatigue (n = 1). No patient achieved a complete or partial response. Vinfosiltine does not appear to have significant single-agent activity in advanced breast cancer at the doses and the schedules used in our study. PMID- 7882461 TI - Effects of hexadecylphosphocholine on fatty acid metabolism: relation to cytotoxicity. AB - The cytotoxicity of the antineoplastic drug hexadecylphosphocholine (HePC) was determined in a human monocytic tumor cell line, THP1, and in primary cultures of rat mesangial cells. Both cell types were susceptible to HePC toxicity, the concentrations producing 50% inhibition of cell viability (LD50 values) being 7 micrograms/ml for THP1 cells and 19 micrograms/ml for mesangial cells. The degree of toxicity was dependent on the culture conditions. In the absence of serum, HePC was highly toxic independent of cell proliferation. As a potential molecular mechanism, the effect of HePC on long-chain fatty acyl metabolism was investigated. HePC had no effect on fatty acid incorporation into cellular lipids or on release of fatty acids from lipid stores. The distribution of labeled fatty acids, however, was shifted from the phospholipid fraction to the triacylglycerol fraction. This effect was in accordance with an inhibition of the activity of the reacylating enzyme lysophosphatide acyltransferase. There was, however, no correlation between the interference with fatty acid distribution and HePC cytotoxicity in vitro. The data argue against interference with membrane fatty acid metabolism as a necessary prerequisite of HePC toxicity, the mechanism of which remains to be elucidated. PMID- 7882463 TI - Determination of platinum in plasma of patients affected by inoperable lung carcinoma treated with radiotherapy and concurrent low-dose continuous infusion of cis-dichlorodiammine platinum(II). AB - Platinum microquantities were determined in plasma of patients affected by lung carcinoma during treatment with radiotherapy (RT) and concurrent low-dose continuous infusion of cis-dichlorodiammineplatinum(II) (CDDP). RT was given at 50 Gy in continuous course; CDDP was continuously infused at 4 mg/m2 daily for 100 h/week for 5 weeks, and the infusions were separated by 68 h of rest. The percentage of free drug versus total drug in plasma was about 3%. It did not vary with therapy duration and was not significantly different from that found in 5 day continuous infusions at much higher daily doses. Nevertheless, maximal values of free Pt in plasma were very low and agreed with the low level of CDDP toxicity encountered on the present administration schedule. PMID- 7882464 TI - Lithium concentrations during cisplatin-based chemotherapy: evidence for renal interaction. PMID- 7882465 TI - Evaluation of myocardial cell damage by In-111-monoclonal antimyosin antibodies in patients under chronic tricyclic antidepressant drug treatment. AB - BACKGROUND: The capability of chronic tricyclic antidepressant drug (TAD) treatment to elicit myocardial damage has been a subject of debate. Lack of an adequate noninvasive method to detect such damage has prevented an in-depth study. METHODS AND RESULTS: A prospective study with In-111-monoclonal antimyosin antibodies was undertaken in a series of 21 young patients with major depression on TADs and a control group of 19 healthy subjects. A heart-to-lung ratio (HLR) of antimyosin uptake was used to discriminate normal from abnormal scans. HLR in healthy subjects was 1.39 +/- 0.08. Patients on imipramine (HLR, 1.41 +/- 0.09) or clomipramine (HLR, 1.44 +/- 0.06) showed normal studies. Those under amitriptyline had a higher HLR (1.58 +/- 0.12) compared with nonamitriptyline or normal groups (P < .05). None of the 15 patients on imipramine or clomipramine showed abnormal HLR, while 3 of 6 on amitriptyline did (P < .01). In these 3 patients, uptake decreased or disappeared after drug withdrawal. Ejection fraction was normal in every patient. CONCLUSIONS: Monoclonal antimyosin antibody studies are normal in imipramine- and clomipramine-treated patients. Antibody uptake in those under amitriptyline treatment, which disappears after drug withdrawal, would suggest early evidence of myocardial toxicity. PMID- 7882466 TI - Loss of flow-dependent coronary artery dilatation in patients with hypertension. AB - BACKGROUND: Abnormal endothelium-dependent coronary response to acetylcholine has been shown in patients with essential hypertension. We tested the hypothesis that flow-dependent dilatation, which has been shown in normal human coronary arteries, is impaired in hypertensive patients. METHODS AND RESULTS: The coronary vasomotor response to maximal increase of blood flow induced by papaverine was studied in 10 control subjects and in 14 hypertensive patients with no other risk factors and angiographically normal coronary arteries. After the injection of papaverine in the midportion of the left anterior descending coronary artery (LAD), the diameter of the proximal LAD (LAD1) was measured by quantitative angiography, whereas that of the proximal circumflex artery (LCx) served as control segment. Estimates of coronary blood flow in the distal LAD (LAD2) were calculated by intracoronary Doppler flow velocity measurements. An increase in LAD2 blood flow of 521 +/- 41% (P < .001) in control subjects was associated with a 17.0 +/- 3.3% dilatation of the LAD1 (P < .001) and with no significant change in the diameter of the LCx. In hypertensive patients, despite a comparable increase in LAD2 blood flow of 406 +/- 32% (P < .001), the LAD1 failed to dilate (-0.4 +/- 0.6%, NS). The dilative response to isosorbide dinitrate was similar in control subjects and hypertensive patients (30.0 +/- 4.1%, P < .001 and 21.9 +/- 1.9%, P < .001, respectively). CONCLUSIONS: Thus, the flow-mediated coronary dilatation is lost in hypertensive patients, and this may impair normal dilatation observed in response to an increase in myocardial metabolic demand. PMID- 7882467 TI - Improving active compression-decompression cardiopulmonary resuscitation with an inspiratory impedance valve. AB - BACKGROUND: Active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) has recently been demonstrated to provide significantly more blood flow to vital organs during cardiac arrest. To further enhance the effectiveness of this technique, we tested the hypothesis that intermittent impedance to inspiratory gas exchange during the decompression phase of ACD CPR enhances vital organ blood flow. METHODS AND RESULTS: ACD CPR was performed with a pneumatically driven automated compression-decompression device in a porcine model of ventricular fibrillation (VF). Nine pigs were randomized to receive ACD CPR alone, while 8 pigs received ACD CPR plus intermittent impedance to inspiratory gas exchange with a threshold valve set to 40 cm H2O. Results comparing 2 minutes of ACD CPR alone versus ACD CPR with the inspiratory impedance threshold valve (ITV) revealed significantly higher mean (+/- SEM) coronary perfusion pressures (diastolic aortic minus diastolic right atrial pressures) in the ITV (31.0 +/- 2.3 mm Hg) group versus with ACD CPR alone (21 +/- 3.6 mm Hg) (P < .05). Total left ventricular and cerebral blood flows, determined by radiolabeled microspheres, were 0.77 +/- 0.095 and 0.47 +/- 0.06 mL/min per gram, respectively, with ACD CPR plus the ITV versus 0.45 +/- 0.1 and 0.32 +/- 0.016 mL/min per gram, respectively, with ACD CPR alone (P < .05). Similar improvements in the ITV group were observed after 7 minutes of ACD CPR. After 16 minutes of VF and 13 minutes of ACD CPR, 6 of 8 pigs in the ITV group were successfully resuscitated with less than three successive 150-J shocks, whereas only 2 of 9 pigs with ACD CPR alone were resuscitated with equivalent energy levels (P < .02). With up to three additional and successive 200-J shocks, all pigs in the ITV group and 7 of 9 pigs with ACD CPR alone were resuscitated (P = .18). CONCLUSIONS: Intermittent impedance to inspiratory flow of respiratory gases during ACD CPR significantly improves coronary perfusion pressures and vital organ blood flow and lowers defibrillation energy requirements in a porcine model of VF. PMID- 7882468 TI - Gene for progressive familial heart block type I maps to chromosome 19q13. AB - BACKGROUND: Progressive familial heart block type I (PF-HBI) is a dominantly inherited cardiac bundle-branch conduction disorder that has been traced through nine generations of a large South African kindred. Similar conduction disorders have been reported elsewhere; however, the cause of these diseases is unknown. The aim of the present study was to determine by linkage analysis the approximate chromosomal position of the gene causing PFHBI, thereby allowing family-based diagnosis and the development of positional cloning strategies to identify the causative gene. METHODS AND RESULTS: Eighty-six members of three pedigrees, 39 members of which were affected with PFHBI, were genotyped at four linked polymorphic marker loci mapped to chromosome 19, bands q13.2-q13.3 (chromosome 19q13.2-13.3). Maximum two-point logarithm of the odds scores (which represent the logarithm of the odds ratio of detecting linkage versus nonlinkage) generated were 6.49 (theta = 0) for the kallikrein locus, 5.72 (theta = 0.01) for the myotonic dystrophy locus, 3.44 (theta = 0) for the creatine kinase muscle-type locus and 4.51 (theta = 0.10) for the apolipoprotein C2 locus. The maximum multipoint logarithm of the odds score was 11.6, with the 90% support interval positioning the PFHBI locus within a 10 cM distance centering on the kallikrein 1 locus. CONCLUSIONS: The gene for PFHBI maps to an area of approximately 10 cM on chromosome 19q13.2-13.3. There are several candidate genes in this interval; although a recombination event ruled out the myotonic dystrophy locus from direct involvement with PFHBI, the proximity of these two loci may be relevant to the observed cardiac abnormalities of myotonic dystrophy. The results provide a means of DNA-based diagnosis in the families studied and a foundation for cloning studies to identify the causative gene. PMID- 7882469 TI - Genetic diagnosis with the denaturing gradient gel electrophoresis technique improves diagnostic precision in familial hypercholesterolemia. AB - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant inherited disorder of lipid metabolism caused by mutations in the LDL receptor gene. FH is characterized clinically by elevated LDL cholesterol level and premature coronary disease. Diagnosing FH on clinical grounds may be difficult, and previous genetic methods are too cumbersome for routine use except in the few populations with FH founder mutations. A simple mutation screening technique based on denaturing gradient gel electrophoresis (DGGE) has been highly useful in detecting mutations in other genes, and in the present study we evaluated the diagnostic potential of this method for the diagnosis of FH. METHODS AND RESULTS: Conditions for screening exon 3 of the LDL receptor gene using the DGGE technique were established and 14 Danish FH families were examined. An index patient from 1 family had an abnormal DGGE pattern; consequently, an examination of exon 3 of the LDL receptor gene in 21 members of this patient's family was done. The DGGE pattern was seen only in patients with a definite clinical diagnosis of FH. Subsequent sequencing of exon 3 of the LDL receptor gene in these individuals revealed the presence of the French-Canadian type 4 Trp66-Gly mutation. However, in 4 of 11 cases in which a definite clinical diagnosis of FH had been made, the inheritance of the French-Canadian type 4 mutation could be rejected on the basis of genetic analysis. CONCLUSIONS: Introduction of a simple genetic analysis based on DGGE may improve the precision of diagnosis in FH families. PMID- 7882470 TI - Cardiac allograft vascular disease. Relationship to microvascular cell surface markers and inflammatory cell phenotypes on endomyocardial biopsy. AB - BACKGROUND: Cardiac allograft vascular disease is characterized by accelerated and diffuse intimal proliferation involving both the microvasculature and epicardial vessels. Because in vivo documentation of this complication is now possible with intracoronary ultrasound imaging, we can examine the relationship of intimal proliferation to markers of immunity and endothelial activation. We hypothesize that alterations of microvascular cell surface markers likely mirror changes in the epicardial vessels that may be important in the pathophysiology of intimal proliferation. METHODS AND RESULTS: Forty-three heart transplant patients were examined by intracoronary ultrasound more than 1 year after transplantation, and these images were analyzed to obtain mean intimal thickness and intimal thickness class (I through IV), calculated from the mean thickness and circumferential involvement. Right ventricular endomyocardial biopsies obtained at the time of intracoronary ultrasound were examined by immunohistochemistry to detect microvascular expression of histocompatibility leukocyte antigen (HLA) classes I and II (HLA ABC, DR, DP, and DQ); endothelial-specific antigen detected by the monoclonal antibody E 1.5; intercellular adhesion molecules (ICAM-1); CD4+ and CD8+ lymphocytes and macrophages (CD 14+). Microvascular antigen expression was graded 1 through 5 on the basis of the diffuseness of positive staining. The number of each inflammatory cell phenotype present per high-power field was counted. By ANOVA, scores for HLA DR, HLA DQ, and E1.5 expression were lower in intimal thickness classes II, III, and IV compared with class I. This inverse relationship was significant by linear regression analysis of mean intimal thickness. Inflammatory cells were not significantly correlated with intimal thickening. Rejection incidence was higher, and time since transplantation longer, in intimal thickness classes II, III, and IV compared with class I. CONCLUSION: Transplant coronary artery intimal proliferation is associated with alteration of microvascular endothelial cell surface markers. These changes in cell surface antigen expression could provide the substrate for coronary artery intimal proliferation and narrowing. PMID- 7882471 TI - Angiotensin-converting enzyme genotype in children and coronary events in their grandparents. AB - BACKGROUND: It has been suggested that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary artery disease. The D/D genotype, which is associated with higher levels of circulating ACE than the I/D or I/I genotype, has been found significantly more frequently in patients with myocardial infarction and also in individuals with a parental history of myocardial infarction. METHODS AND RESULTS: We explored the distribution of the ACE genotype in 404 school children, aged 6 to 13 years, and related the distribution to the number of their grandparents who had had vascular events. We found a significant association between the number of grandparents who had had coronary events and the ACE genotype (P = .01). In children with two or more grandparents who had had coronary events, there was an excess of both D/D (odds ratio = 2.8 [95% confidence interval = 1.16-6.56]) and I/D (odds ratio = 1.4 [95% confidence interval = 0.62-3.25]) genotypes compared with I/I genotypes. In addition, there was an association between the ACE genotype and lipoprotein(a) levels in children (P = .07). Both the ACE genotype and lipoprotein(a) were found to contribute significantly (P = .0042) and independently to family history of coronary artery disease, with the ACE genotype proving to be more predictive than lipoprotein(a) levels. CONCLUSIONS: We conclude that the I/D polymorphism of the ACE gene is an important independent risk factor for coronary artery disease and is more predictive that lipoprotein(a). The I/D polymorphism is not only associated with a parental history of myocardial infarction but also with coronary artery disease in second degree relatives. A further study to explore the relation between the I/D polymorphism and circulating levels of lipoprotein(a) is indicated. PMID- 7882472 TI - Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Results from an international trial of 41,021 patients. GUSTO-I Investigators. AB - BACKGROUND: Despite remarkable advances in the treatment of acute myocardial infarction, substantial early patient mortality remains. Appropriate choices among alternative therapies and the use of clinical resources depend on an estimate of the patient's risk. Individual patients reflect a combination of clinical features that influence prognosis, and these factors must be appropriately weighted to produce an accurate assessment of risk. Prior studies to define prognosis either were performed before widespread use of thrombolysis or were limited in sample size or spectrum of data. Using the large population of the GUSTO-I trial, we performed a comprehensive analysis of relations between baseline clinical data and 30-day mortality and developed a multivariable statistical model for risk assessment in candidates for thrombolytic therapy. METHODS AND RESULTS: For the 41,021 patients enrolled in GUSTO-I, a randomized trial of four thrombolytic strategies, relations between clinical descriptors routinely collected at initial presentation, and death within 30 days (which occurred in 7% of the population) were examined with both univariable and multivariable analyses. Variables studied included demographics, history and risk factors, presenting characteristics, and treatment assignment. Risk modeling was performed with logistic multiple regression and validated with bootstrapping techniques. Multivariable analysis identified age as the most significant factor influencing 30-day mortality, with rates of 1.1% in the youngest decile (< 45 years) and 20.5% in patients > 75 (adjusted chi 2 = 717, P < .0001). Other factors most significantly associated with increased mortality were lower systolic blood pressure (chi 2 = 550, P < .0001), higher Killip class (chi 2 = 350, P < .0001), elevated heart rate (chi 2 = 275, P < .0001), and anterior infarction (chi 2 = 143, P < .0001). Together, these five characteristics contained 90% of the prognostic information in the baseline clinical data. Other significant though less important factors included previous myocardial infarction, height, time to treatment, diabetes, weight, smoking status, type of thrombolytic, previous bypass surgery, hypertension, and prior cerebrovascular disease. Combining prognostic variables through logistic regression, we produced a validated model that stratified patient risk and accurately estimated the likelihood of death. CONCLUSIONS: The clinical determinants of mortality in patients treated with thrombolytic therapy within 6 hours of symptom onset are multifactorial and the relations complex. Although a few variables contain most of the prognostic information, many others contribute additional independent prognostic information. Through consideration of multiple characteristics, including age, medical history, physiological significance of the infarction, and medical treatment, the prognosis of an individual patient can be accurately estimated. PMID- 7882473 TI - Complex coronary artery lesion morphology influences results of stress echocardiography. AB - BACKGROUND: The likelihood of a positive response with dipyridamole stress echocardiography (DSE) is directly related to the extent and severity of angiographically assessed coronary artery disease. Whether coronary lesion morphology--a known predictor of adverse cardiac events--may also modulate stress echo results remains unknown. The objective of our study was to assess the relation between stenosis lesion morphology and stress echocardiographic results. METHODS AND RESULTS: High-dose (up to 0.84 mg/kg over 10 minutes) DSE and coronary angiographic data of 68 in-hospital patients (39 with stable angina, 29 with angina at rest) with nonoccluding, single-vessel disease at angiography and no previous myocardial infarction were analyzed. DSE was performed in all patients within 3 days of coronary angiography. An angiographic lesion was considered complex when irregular borders and/or intraluminal lucencies suggestive of ulcer and/or thrombus were present. According to angiographic lesion morphology, two groups were identified: group 1, with simple coronary lesions, and group 2, with complex coronary lesions. The two groups were matched for number of patients (n = 34 in each group), age (group 1, 59 +/- 9 versus group 2, 59 +/- 10 years, P = NS), and coronary artery stenosis severity by quantitative coronary angiography (group 1, 60 +/- 7% versus group 2, 58 +/- 6% diameter reduction, P = NS). The sensitivity of DSE was lower in patients of group 1 when compared with group 2 (53% versus 85%, P < .001). Among positive DSE, the low-dose (0.56 mg/kg over 4 minutes) positivity was less frequent in group 1 than in group 2 patients (17% versus 62%, P < .01). Exercise ECG was completed in 66 patients, and it was positive (> .1 mV ST-segment shift from baseline) in 20 out of 33 group 1 and in 22 out of 33 group 2 patients (61% versus 67%, P = NS). The peak rate-pressure product tended to be higher in group 1 than in group 2 patients (257 +/- 52 versus 240 +/- 64 mm Hg x beats per minute x 10(2), P = NS). CONCLUSIONS: In patients with single-vessel disease without coronary occlusion or previous myocardial infarction, coronary lesion morphology of the complex type is associated with a higher DSE sensitivity and with a greater prevalence of low-dose, positive responses. Presence of irregular plaque contours, not only plaque geometry, is important in modulating stress responses in the presence of angiographically assessed coronary artery disease. PMID- 7882474 TI - Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance. AB - BACKGROUND: The placement of stents in coronary arteries has been shown to reduce restenosis in comparison to balloon angioplasty. However, clinical use of intracoronary stents is impeded by the risk of subacute stent thrombosis and complications associated with the anticoagulant regimen. To reduce these complications, the hypothesis that systemic anticoagulation is not necessary when adequate stent expansion is achieved was prospectively evaluated on a consecutive series of patients who received intracoronary stents. METHODS AND RESULTS: From March 1993 to January 1994, 359 patients underwent Palmaz-Schatz coronary stent insertion. After an initial successful angiographic result with < 20% stenosis by visual estimation had been achieved, intravascular ultrasound imaging was performed. Further balloon dilatation of the stent was guided by observation of the intravascular ultrasound images. All patients with adequate stent expansion confirmed by ultrasound were treated only with antiplatelet therapy (either ticlopidine for 1 month with short-term aspirin for 5 days or only aspirin) after the procedure. Clinical success (procedure success without early postprocedural events) at 2 months was achieved in 338 patients (94%). With an inflation pressure of 14.9 +/- 3.0 atm and a balloon-to-vessel ratio of 1.17 +/- 0.19, optimal stent expansion was achieved in 321 of the 334 patients (96%) who underwent intravascular ultrasound evaluation, with these patients receiving only antiplatelet therapy after the procedure. Despite the absence of anticoagulation, there were only two acute stent thromboses (0.6%) and one subacute stent thrombosis (0.3%) at 2-month clinical follow-up. Follow-up angiography at 3 to 6 months documented two additional occlusions (0.6%) at the stent site. At 6-month clinical follow-up, angiographically documented stent occlusion had occurred in 5 patients (1.6%). At 6-month clinical follow-up, there was a 5.7% incidence of myocardial infarction, a 6.4% rate of coronary bypass surgery, and a 1.9% incidence of death. Emergency intervention (emergency angioplasty or bailout stent) for a stent thrombosis event was performed in 3 patients (0.8%). The overall event rate was relatively high because of intraprocedural complications that occurred in 16 patients (4.5%). Intraprocedural complications, however, decreased to 1% when angiographically appropriately sized balloons were used for final stent dilations. There was one ischemic vascular complication that occurred at the time of the procedure and one ischemic vascular complication that occurred at the time of angiographic follow-up. By 6 months, repeat angioplasty for symptomatic restenosis was performed in 47 patients (13.1%). CONCLUSIONS: The Palmaz-Schatz stent can be safely inserted in coronary arteries without subsequent anticoagulation provided that stent expansion is adequate and there are no other flow-limiting lesions present. The use of high-pressure final balloon dilatations and confirmation of adequate stent expansion by intravascular ultrasound provide assurance that anticoagulation therapy can be safely omitted. This technique significantly reduces hospital time and vascular complications and has a low stent thrombosis rate. PMID- 7882475 TI - Long-term effects of angiopeptin treatment in coronary angioplasty. Reduction of clinical events but not angiographic restenosis. European Angiopeptin Study Group. AB - BACKGROUND: Angiopeptin is a cyclic octapeptide analogue of somatostatin that has been shown to limit myointimal thickening of arteries in balloon injury models and to restore the vasodilating response to acetylcholine. A randomized, double blind placebo controlled trial was conducted to assess the effect of angiopeptin in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: Patients received a continuous infusion of either placebo or angiopeptin subcutaneously 6 to 24 hours before PTCA and for 4 days after PTCA (3 mg per 24 hours before PTCA followed by 6 mg per 24 hours after PTCA and for the remaining period). A 1.5-mg bolus dose of placebo or angiopeptin was given at PTCA. Aspirin (acetylsalicylic acid, 150 mg/d) was administered throughout the study period. Coronary angiograms obtained before and after PTCA and at 6-month follow-up were subjected to computerized quantification. Clinical follow-up was performed after 12 months. Primary clinical end points were death, myocardial infarction, coronary artery bypass surgery, or repeat PTCA. In total, 553 patients with 742 lesions were randomized. Clinical follow-up was available for all 553 patients. Angiopeptin decreased the clinical events during 12 months of follow-up from 36.4% in the placebo-treated group to 28.4% in the angiopeptin treated patients (P = .046). Quantitative angiography after PTCA and at follow-up was available in 423 of 455 patients who underwent successful PTCA. The minimal lumen diameter at follow-up was 1.52 +/- 0.64 mm in the angiopeptin-treated group compared with 1.52 +/- 0.64 mm in the placebo-treated patients (P = .96). The late losses were 0.31 +/- 0.59 and 0.30 +/- 0.62 mm (P = .81) and the restenosis rates (> 50% diameter stenosis at follow-up) were 36% and 37% (P = .85) in the angiopeptin- and placebo-treated groups, respectively. CONCLUSIONS: In this study, angiopeptin significantly decreased the incidence of clinical events, principally the rate of revascularization procedures. In contrast, no significant effect was seen on angiographic variables. PMID- 7882476 TI - Prediction of reversible ischemia after revascularization. Perfusion and metabolic studies with positron emission tomography. AB - BACKGROUND: Accurate noninvasive determination of myocardial viability is of paramount importance for the clinical identification of patients who will benefit most from revascularization. The preserved metabolic activity in the myocardium, as studied with positron emission tomography (PET), has been considered a gold standard for this purpose. However, recent reports show that moderate hypoperfusion or stress-induced ischemia may represent reversible ischemia. The present study was undertaken to compare the value of perfusion and metabolic studies with PET for predicting improvement in wall motion after revascularization. METHODS AND RESULTS: Of 61 patients who had regional asynergy and underwent PET before revascularization, 43 patients who had successful revascularization were included in the study. Each patient underwent rest-stress 13N-ammonia perfusion scans and 18F-fluorodeoxyglucose (FDG) scan at rest while in a fasting state. Reversible ischemia was considered to be present when the resting perfusion was > or = 50% of the peak value, stress-induced hypoperfusion was present, or an increase in FDG uptake was observed. Of 130 asynergy segments, 51 segments had improved wall motion after revascularization. The positive and negative predictive values for improvement in asynergy were 48% and 87% by the rest perfusion study, 63% (P = .05 versus the rest value) and 87% by the rest stress perfusion study, and 76% (P < .01 versus the rest value) and 92% by the FDG study. CONCLUSIONS: FDG PET provided the best predictive value for improvement in wall motion after revascularization. On the other hand, 13N ammonia PET is useful for predicting nonreversible myocardial scarring when it shows severe hypoperfusion at rest or hypoperfusion without stress-induced ischemia. PMID- 7882477 TI - Occult and frequent transmission of atherosclerotic coronary disease with cardiac transplantation. Insights from intravascular ultrasound. AB - BACKGROUND: Transplant coronary artery disease is a major cause of morbidity and mortality after cardiac transplantation. However, limited data exist regarding the potential contribution of coronary atherosclerosis in the donor heart to cardiac-allograft vasculopathy. METHODS AND RESULTS: We performed quantitative coronary angiography and intravascular ultrasound imaging in 50 of 62 consecutive heart-transplant recipients (40 men, 10 women, mean age, 53 +/- 9 years) 4.6 +/- 2.6 weeks after transplantation. The donor population consisted of 30 men and 20 women (mean age, 32 +/- 12 years). Ultrasound imaging visualized all three coronary arteries in 22 patients, two coronary arteries in 23, and one coronary artery in 5. Ultrasound imaging detected coronary atherosclerosis (intimal thickness > or = 0.5 mm) in 28 patients (56%). However, the angiography was abnormal in only 13 patients (26%). The sensitivity and specificity of coronary angiography were 43% and 95%, respectively. With ultrasound, the average atherosclerotic plaque thickness was 1.3 +/- 0.6 mm and the cross-sectional area narrowing was 34 +/- 16%. Atherosclerotic involvement frequently was focal (85%), eccentric (mean eccentricity index, 87 +/- 8), and near arterial bifurcations. Donors of the transplant recipients with coronary atherosclerosis were older than those without atherosclerosis (37 +/- 12 versus 25 +/- 10 years, P = .001). Maximal intimal thickness correlated with donor age (r = .54, P = .0001). Multivariate analysis demonstrated that donor age (P = .0001), male sex of donor (P = .0006), and recipient age (P = .03) were independent predictors of atherosclerosis. CONCLUSIONS: Coronary atherosclerosis is frequently but inadvertently transmitted by means of cardiac transplantation from the donor to the recipient. Long-term outcomes of donor-transmitted coronary artery disease will require further evaluation. PMID- 7882478 TI - Papillary muscle perfusion pattern. A hypothesis for ischemic papillary muscle dysfunction. AB - BACKGROUND: The pathogenesis of posterior papillary muscle dysfunction is poorly understood. We hypothesized that papillary muscle perfusion pattern may explain the higher prevalence of posterior papillary muscle dysfunction after myocardial infarction. METHODS AND RESULTS: Twenty patients were monitored by transesophageal echocardiography during coronary surgery. Superselective coronary graft injections of 0.2 to 0.5 mL of sonicated albumin microbubbles were performed to assess graft patency and papillary muscle perfusion. Thirty-five graft injections were analyzed: 13 in the right coronary artery, 15 in an obtuse marginal branch, 1 in the left anterior descending coronary artery, and 6 in the first diagonal branch. The posterior papillary muscle was opacified in 16 patients, 11 from the right coronary artery and 5 from one obtuse marginal branch. In 10 of 16 patients (63%), the papillary muscle was perfused by one vessel, while in 6 of 16 (37%), it was perfused by two vessels. The anterior papillary muscle was opacified in 14 patients. Ten patients (71%) had double vessel and 4 (29%) had single-vessel supply. In the subgroup of 10 patients with old inferior myocardial infarction, mitral regurgitation was present only among those 6 with single rather than double blood supply (P < .05). CONCLUSIONS: Myocardial infarction may cause papillary muscle dysfunction when the blood supply is provided by one rather than two vessels, as is more frequently the case with the posterior rather than the anterior papillary muscle. PMID- 7882479 TI - Evaluation of exercise capacity using submaximal exercise at a constant work rate in patients with cardiovascular disease. AB - BACKGROUND: Symptom-limited incremental exercise tests are used to estimate the severity of cardiovascular disease and the patient's daily activity. However, there is a need for objective parameters for submaximal exercise. To test the hypothesis that a decrease in maximal exercise capacity can be estimated by oxygen uptake (VO2) kinetics, we measured the time constant of VO2 both during the onset of constant work rate exercise at 50 W and during recovery from this exercise and compared it with data obtained during maximal exercise in patients with cardiovascular disease and in normal subjects. METHODS AND RESULTS: A total of 34 patients with cardiovascular disease and 14 normal subjects performed 6 minutes of 50-W constant work rate exercise and an incremental exercise test to the symptom-limited maximum on a cycle ergometer. VO2 was calculated from respiratory gas analysis on a breath-by-breath basis. The time constant of VO2 during the onset of 50-W exercise was 61.4 +/- 15.2 seconds in patients with cardiovascular disease, significantly longer (the kinetics of VO2 were slower) than that in normal subjects (48.8 +/- 10.4 seconds, P = .008). The time constant of VO2 during the onset of exercise was significantly negatively correlated with peak VO2 (r = -.67) and maximal work rate (r = -.66). The time constant during recovery, which did not differ significantly from that of exercise, was also prolonged in patients with cardiovascular disease; it showed a negative correlation with peak VO2 (r = -.63) and maximum work rate (r = -.54). CONCLUSIONS: The time constant of VO2 during and after recovery from 50 W of constant work rate exercise, which does not require the subject's maximal effort, is a useful and objective measure of exercise capacity in patients with mild to moderate cardiovascular disease. PMID- 7882480 TI - Effect of continuous positive airway pressure on intrathoracic and left ventricular transmural pressures in patients with congestive heart failure. AB - BACKGROUND: Continuous positive airway pressure (CPAP) can improve cardiac function in patients with congestive heart failure (CHF). We hypothesized that this effect might be related to CPAP-induced increases in intrathoracic pressure, which would reduce left ventricular transmural pressure (LVPtm) during systole, thereby decreasing left ventricular afterload. METHODS AND RESULTS: The effect of graduated CPAP from 0 to 10 cm H2O on the above variables was examined over a 75 minute period and compared with a 75-minute time control period without CPAP in two groups of subjects: 15 patients with CHF and 9 healthy subjects. Intrathoracic pressure was estimated from esophageal pressure (Pes), and systolic LVPtm, a determinant of left ventricular afterload, was assessed by subtracting Pes during systole from systolic blood pressure. Cardiac index (CI) was assessed by Doppler echocardiography. At baseline, inspiratory Pes amplitude, which reflects inspiratory muscle force generation, was greater in the patients with CHF than in the healthy group (9.9 +/- 0.8 versus 5.5 +/- 0.4 mm Hg, P < .001). In addition, systolic Pes, which represents the relative contribution of intrathoracic pressure to LVPtm, was more negative in the patients with CHF than in the healthy group (-4.1 +/- 0.3 versus -2.2 +/- 0.1 mm Hg, P < .001). While on CPAP of 10 cm H2O, inspiratory Pes amplitude decreased and systolic Pes increased significantly in the group with CHF (from 11.1 +/- 1.1 to 7.5 +/- 1.1 mm Hg, P < .025 and from -4.7 +/- 0.6 to 0.6 +/- 0.6 mm Hg, P < .001, respectively), but CPAP had no effect on these variables in the healthy subjects. Compared with the equivalent time control period, Pes amplitude x respiratory rate decreased significantly while on CPAP in both the group with CHF (from 188 +/- 22 to 112 +/ 17 mm Hg x breaths per minute, P < .005) and the healthy group (from 82 +/- 8 to 60 +/- 6 mm Hg x breaths per minute, P < .05). Compared with time control, systolic LVPtm decreased significantly while on CPAP, from 116.0 +/- 5.3 to 110.3 +/- 4.5 mm Hg (P < .025) in the group with CHF, but did not change in the healthy group. Moreover, systolic LVPtm x heart rate decreased significantly in the group with CHF (from 80.55 +/- 5.27 to 71.83 +/- 4.73 mm Hg x beats per minute/100, P < .005) but not in the healthy group. CI decreased significantly while on CPAP in the healthy group (P < .025) but did not change in the group with CHF. CONCLUSIONS: In patients with CHF, the inspiratory muscles generate greater force per breath and systolic Pes contributes more to LVPtm than in healthy subjects. By increasing intrathoracic pressure in patients with CHF, CPAP unloaded inspiratory muscles and reduced left ventricular afterload without compromising CI. PMID- 7882481 TI - Impaired endothelium-dependent vasodilation in patients with essential hypertension. Evidence that nitric oxide abnormality is not localized to a single signal transduction pathway. AB - BACKGROUND: Patients with essential hypertension have abnormal endothelium dependent vascular relaxation, largely related to reduced bioactivity of nitric oxide (NO). The purpose of the present investigation was to determine whether this defect is due to a deficit at the specific intracellular signal-transduction pathway level or is a consequence of a more generalized endothelial abnormality. METHODS AND RESULTS: The responses of the forearm vasculature to acetylcholine and bradykinin (endothelium-dependent agents that act through different signal transduction pathways) and to sodium nitroprusside (a direct dilator of vascular smooth muscle) were studied in 10 hypertensive patients (5 men, 5 women; aged 48 +/- 9 years old [mean +/- SD]) and 12 control subjects (6 men, 6 women; aged 48 +/- 7 years old). To determine the contribution of NO to bradykinin-induced vasodilation, the vascular responses to bradykinin were also measured after administration of NG-monomethyl-L-arginine, an arginine analogue that inhibits the synthesis of NO. Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography. The response to acetylcholine was significantly blunted in hypertensive patients (maximal blood flow, 7.5 +/- 2 versus 16.6 +/- 8 mL.min-1.100 mL-1 in control subjects [mean +/- SD]; P < .005). Similarly, the vasodilator effect of bradykinin was significantly reduced in hypertensive patients compared with control subjects (maximal blood flow, 8.7 +/- 2 versus 15.8 +/- 6 mL.min-1.100 mL-1 in control subjects; P < .005). A significant correlation was found between the maximal blood flow with acetylcholine and that with bradykinin (r = .89). No significant differences were found between the two groups for vascular response to sodium nitroprusside. NG monomethyl-L-arginine significantly blunted the response to bradykinin in control subjects (maximal blood flow decreased from 15.8 +/- 6 to 10.1 +/- 2 mL.min-1.100 mL-1, P < .003). In contrast, inhibition of NO synthesis did not modify the response to bradykinin in hypertensive patients (maximal blood flow, 8.7 +/- 2 and 8.5 +/- 3 before and during infusion of NG-monomethyl-L-arginine, respectively; P = NS). As a consequence, the response to bradykinin after inhibition of NO synthesis was not significantly different between the two groups. CONCLUSIONS: Patients with essential hypertension have impaired endothelium-dependent vasodilator responses to both acetylcholine and bradykinin. These findings indicate that the endothelial dysfunction in this condition is not related to a specific defect of a single intracellular signal-transduction pathway and suggest a more generalized abnormality of endothelial vasodilator function. PMID- 7882482 TI - Sex, age, and disease affect echocardiographic left ventricular mass and systolic function in the free-living elderly. The Cardiovascular Health Study. AB - BACKGROUND: Left ventricular (LV) hypertrophy, as measured by M-mode echocardiography, is an independent predictor of mortality and/or morbidity from coronary heart disease (CHD). LV global and segmental systolic dysfunction also have been associated with myocardial ischemia and cardiovascular morbidity and mortality. Echocardiographic data, especially two-dimensional, have not been available previously from multicenter-based studies of the elderly. This report describes the distribution and relation at baseline of echocardiographic LV mass and global and segmental LV wall motion to age, sex, and clinical disease category in the Cardiovascular Health Study (CHS), a cohort of 5201 men and women (4850 white) 65 years of age and older. METHODS AND RESULTS: M-mode LV mass adjusted for body weight increased modestly with age (P < .0001), increasing less than one gram per year increase in age for both men and women. After adjustment for weight, LV mass was significantly greater in men than in women and in participants with clinical CHD compared with participants with neither clinical heart disease nor hypertension (both P < .001). Across all CHS age subgroups, the difference in weight-adjusted LV mass by sex was greater in magnitude than the difference related to clinical CHD. M-mode measurements of LV mass could not be made in 34% of CHS participants, and this was highly related to age (29% in the 65 to 69 year versus 50% in the 85+ year age group, P < .001) and other risk factors. In participants with clinical CHD and with neither clinical heart disease nor hypertension, LV ejection fraction and segmental wall motion abnormalities were more prevalent in men than women (all P < .001). Of interest, 0.5% of men and 0.4% of women with neither clinical heart disease nor hypertension had LV segmental wall motion abnormalities, suggesting silent disease, compared with 26% of men and 10% of women in the clinical CHD group (P < .0001). Multivariate analyses revealed male sex and presence of clinical CHD (both P < .001) to be independent predictors of LV akinesis or dyskinesis. CONCLUSIONS: Significant baseline relations were detected between differences in sex, prevalent disease status, and echocardiographic measurements of LV mass and systolic function in the CHS cohort. Age was weakly associated with LV mass measurements and LV ejection fraction abnormalities. These relations should be considered in evaluating the preclinical and clinical effects of CHD risk factors in the elderly. PMID- 7882483 TI - Risk factors for sudden cardiac death in middle-aged British men. AB - BACKGROUND: Risk factors specific to sudden cardiac death (SCD), ie, death within 1 hour after onset of symptoms, have been poorly identified, although recent findings from the present study incriminate heavy drinking and elevated heart rate. This paper examines the relations between a wide range of established and potential risk factors for ischemic heart disease (IHD) and SCD to identify independent risk factors for SCD and factors that might particularly or specifically relate to SCD. METHODS AND RESULTS: We present a prospective study of a cohort that was drawn from general practices in 24 British towns of 7735 middle-aged men who were followed up for 8 years. During 8 years of follow-up, the men experienced 488 major IHD events (nonfatal and fatal), of which 117 (24%) were classified as SCD. Age, preexisting IHD, arrhythmia, systolic blood pressure, blood cholesterol, elevated heart rate (> or = 90 beats per minute), physical activity (all, P < .05), and, to a lesser extent, smoking (P = .06), HDL cholesterol (P < .07), and elevated hematocrit (> or = 46%, P < .09) emerged as independent risk factors for SCD after adjustment for a wide range of factors. Diabetes was not found to be associated with SCD, and forced expiratory volume in 1 second, body mass index, white blood cell count, and antihypertensive drugs were not associated with risk of SCD after adjustment. When examined in relation to non-sudden IHD deaths and nonfatal myocardial infarction, elevated heart rate, heavy drinking, and arrhythmia emerged as factors that appear to be specific or particular to SCD. These three factors and age and blood cholesterol were associated with an increased risk of SCD in men both with and without preexisting IHD. Physical activity, systolic blood pressure, and current smoking were associated with SCD only in men without preexisting IHD. HDL cholesterol and hematocrit were strong predictors of SCD only in men with preexisting IHD. CONCLUSIONS: Three risk factors appear to be specific or particular to the risk of SCD, and these and other risk factors operate differently in patients with versus those without preexisting IHD. These findings have implications for the causes and prevention of SCD. PMID- 7882485 TI - Endogenous adenosine is an antiarrhythmic agent. AB - BACKGROUND: Adenosine administered intravenously terminates supraventricular tachycardias (SVT) involving the AV node as part of the reentrant circuit. Dipyridamole increases interstitial myocardial levels of this nucleoside. This study was designed to determine whether intravenous dipyridamole increases coronary sinus plasma adenosine concentrations ([Ado]cs) in humans to levels sufficient to alter electrophysiological parameters and terminate SVT. METHODS AND RESULTS: A custom-designed catheter and syringe for sampling blood for measurement of [Ado]cs was placed in the coronary sinuses of 7 patients. [Ado]cs and refractory periods and conduction characteristics of the atrium and AV node were determined after autonomic blockade and dipyridamole infusion (5 micrograms.kg-1.min-1 after a loading dose of 0.56 mg/kg). The atrial effective and functional refractory periods remained unchanged after dipyridamole infusion. In contrast, the AV nodal functional refractory period increased from 350 +/- 32 to 381 +/- 41 milliseconds (P = .03); the Wenckebach cycle length also increased from 309 +/- 47 to 350 +/- 57 milliseconds (P < .0001). Coincident with these changes, [ADO]cs increased from 0.18 +/- 0.11 to 0.31 +/- 0.12 mumol/L (P = .02). In another 10 patients with AV or AV nodal reentrant tachycardia, SVT was induced, and coronary sinus blood samples were drawn. Dipyridamole was infused, and coronary sinus blood samples were obtained after 15 minutes or coincident with termination of SVT. Mean [ADO]cs increased from 0.17 +/- 0.06 mumol/L during SVT to 0.38 +/- 0.21 mumol/L after dipyridamole (P = .02). Mean tachycardia cycle length increased from 334 +/- 132 to 375 +/- 139 milliseconds (P = .02); this effect was confined to the AV node, as demonstrated by an increase in AH interval from 171 +/- 144 to 214 +/- 140 milliseconds (P = .003). SVT terminated with the infusion of dipyridamole in 4 of the 10 patients. CONCLUSIONS: Administration of dipyridamole is associated with elevation of [ADO]cs, with coincident prolongation of the mean Wenckebach cycle length and AV nodal functional refractory period. During SVT, dipyridamole leads to prolongation of the AH interval and tachycardia cycle length and to an increase in [ADO]cs, with termination of SVT in four patients. These results support the hypothesis that adenosine may function as an endogenous antiarrhythmic metabolite. PMID- 7882484 TI - Dehydroepiandrosterone sulfate does not predict cardiovascular death in postmenopausal women. The Rancho Bernardo Study. AB - BACKGROUND: High levels of dehydroepiandrosterone sulfate (DHEAS) appear to be associated with a reduced risk of fatal cardiovascular disease (CVD) in men. We examined the association between baseline DHEAS levels and the 19-year CVD and ischemic heart disease (IHD) mortality rates in 942 postmenopausal women free of known heart disease at baseline. METHODS AND RESULTS: The 199 CVD deaths and 102 IHD deaths were not related to baseline DHEAS levels. DHEAS was not related to body mass index, fasting plasma glucose, or family history of coronary heart disease, but significantly higher DHEAS levels were found in women who had elevated total or HDL cholesterol or blood pressure, were current smokers, or were nonusers of estrogen replacement therapy. After we adjusted for age, cholesterol, blood pressure, smoking, estrogen replacement therapy, obesity, fasting plasma glucose, and family history of heart disease, the relative risk of fatal CVD and IHD was 1.11 (95% confidence interval, 0.81 to 1.23) and 0.92 (95% confidence interval, 0.85 to 1.17), respectively, for a 50-microgram/dL decrease in DHEAS. CONCLUSIONS: Although higher DHEAS levels were associated with several major CVD risk factors, they were unrelated to the risk of fatal CVD in women. PMID- 7882486 TI - Truncated biphasic pulses for transthoracic defibrillation. AB - BACKGROUND: Early defibrillation is the single most important factor for improving out-of-hospital ventricular fibrillation resuscitation rates. To achieve the earlier response times required for survival, typically < 6 minutes from time of collapse, it will be necessary to equip a far wider network of first responders (firefighters, police, and other individuals with responsibility for public safety) with small, lightweight, and inexpensive automatic external defibrillators (AEDs). An important step in reducing the size and cost of AEDs will be to improve defibrillation efficacy. Because biphasic waveform defibrillation has had a favorable impact on implantable cardioverter defibrillators (ICDs), there are reasons to believe that biphasic waveforms would also improve transthoracic defibrillators. Our purpose, therefore, was to examine the efficacy of two different low-energy biphasic truncated waveforms referenced to a standard damped sine waveform for transthoracic defibrillation in humans. METHODS AND RESULTS: We prospectively and randomly compared the transthoracic defibrillation efficacy of two different truncated biphasic waveforms, 115 J (70 microF) and 130 J (105 microF), with that of a standard 200-J (36-microF, 28-mH) damped sine wave pulse using right anterior and left lateral thoracic pads (R2 Medical Systems) in 30 cardiac arrest survivors during transvenous ICD surgery. The right anterior patch electrode was used as the cathode and the left lateral thoracic pad as the anode. Transthoracic ventricular defibrillation rescue shocks were tested after a failed transvenous defibrillation shock delivered in the course of ICD testing. Each of the three different rescue shocks was tested in random order in each patient. All shocks were delivered at end expiration. The investigators responsible for determining transthoracic shock efficacy were blinded throughout the study to the transthoracic rescue waveform used. A total of 33 patients were considered for study, but three patients failed to satisfy all entry criteria or did not have a sufficient number of ventricular fibrillation inductions to allow for testing of all three waveforms. Percent efficacy for the three waveforms was then compared in the 30 patients who satisfied entry criteria and completed the protocol. The study population had a mean age of 61 +/- 11 years, with 22 (73%) being men. The mean left ventricular ejection fraction was 0.39 +/- 0.14. Coronary artery disease was present in 22 (73%). The 115-J (70-microF) biphasic pulse, the 130-J (105-microF) biphasic pulse, and the 200-J (36-microF, 28-mH) damped sine wave pulse were equally effective, resulting in a 97% first-shock ventricular defibrillation efficacy rate. Each waveform failed to defibrillate once, with each waveform failing in a different patient. CONCLUSIONS: The results of this study suggest that biphasic truncated transthoracic shocks of low energy (115 and 130 J) are as effective as 200-J damped sine wave shocks used in standard transthoracic defibrillators. This finding may contribute significantly to the miniaturization and cost reduction of transthoracic defibrillators, which could enable the development of a new generation of AEDs appropriate for an expanded group of out-of-hospital first responders and, eventually, layperson use. PMID- 7882487 TI - Right ventricular diastolic function 15 to 35 years after repair of tetralogy of Fallot. Restrictive physiology predicts superior exercise performance. AB - BACKGROUND: We have shown previously that transient right ventricular restriction after tetralogy of Fallot repair prolongs postoperative course. This is a prospective study of right ventricular diastolic performance in late follow-up patients. METHODS AND RESULTS: We studied biventricular function, using Doppler echocardiographic examination. Pulmonary arterial, tricuspid, and mitral valves and superior vena cava Doppler spectrals were obtained in 41 patients (mean age, 28.8 years), 15 to 35 years (mean, 23.6) after complete repair of tetralogy of Fallot. Patients were considered to have evidence of right ventricular restriction if antegrade diastolic flow was detected in the main pulmonary artery, coinciding with atrial systole (A wave), throughout the respiratory cycle. Exercise function was measured by graded treadmill testing with respiratory mass spectrometry. Three patients were excluded because of pulmonary outflow obstruction (Doppler gradient > 40 mm Hg) or residual intracardiac shunts. Of the 38 patients, 37 were in sinus rhythm. Twenty (52.6%) had definite evidence of restriction with an A wave in the pulmonary artery, augmented during inspiration. In all 20 cases, there was superior vena caval flow reversal with atrial systole. Both inspiratory and expiratory transtricuspid E-wave deceleration time was significantly shorter in the restrictive group (P < .003 and P < .03, respectively). All patients had Doppler evidence of pulmonary regurgitation, but its duration was shorter in the restrictive group (P < .01) during inspiration. Cardiothoracic ratio was significantly lower in the restrictive group (P < .01), suggesting less severe pulmonary regurgitation. Both restrictive and nonrestrictive groups had reduced exercise MVO2 compared with healthy age- and sex-matched control subjects, but those with restrictive physiology had significantly better maximum oxygen uptake than the nonrestrictive group (P < .001). CONCLUSIONS: Isolated right ventricular restriction late after tetralogy of Fallot repair is common. Although it reflects abnormal hemodynamics, the A wave contributes to forward pulmonary arterial flow and shortens the duration of pulmonary regurgitation. Consequently, there is less cardiomegaly and improved exercise performance in those patients. PMID- 7882488 TI - Characterization of right ventricular diastolic performance after complete repair of tetralogy of Fallot. Restrictive physiology predicts slow postoperative recovery. AB - BACKGROUND: Prolonged postoperative recovery caused by a low cardiac output state occurs in some patients after complete repair of tetralogy of Fallot. Biventricular systolic function is usually well preserved in these patients. The contribution of impaired diastolic function, particularly of the right ventricle, has not been studied in detail; therefore, we performed a prospective study of right ventricular diastolic function in this patient group. METHODS AND RESULTS: We studied biventricular systolic and diastolic function using Doppler echocardiographic examination. Tricuspid valve, superior vena caval, pulmonary arterial, and mitral valve Doppler spectrals were obtained during the first postoperative day in 35 patients aged 6 months to 45 years who underwent complete repair of tetralogy of Fallot. Biventricular systolic function was grossly normal in all patients. Isolated restrictive right ventricular physiology characterized by pulmonary arterial antegrade flow coincident with atrial systole and associated with prominent retrograde superior vena caval flow was seen in 17 of the 35 patients (group 1). This flow was augmented during the expiratory phase of positive pressure ventilation and abolished or greatly diminished during the inspiratory phase (P < .001). An increase in the duration of pulmonary regurgitation occurred during the inspiratory phase of positive pressure ventilation in these patients (P < .01). All patients with right ventricular restriction had a clinical picture compatible with a low cardiac output state, requiring prolonged stays in intensive care and the hospital. Clinical improvement was mirrored by resolution of the Doppler markers of right ventricular restriction in most of the patients. CONCLUSIONS: Isolated right ventricular restriction is characterized by antegrade diastolic pulmonary arterial flow on Doppler echocardiography and is responsible for the slower postoperative course and clinical evidence of low cardiac output state in some patients after complete repair of tetralogy of Fallot. PMID- 7882489 TI - Capillary distribution in the ventricles of hearts with pulmonary atresia and intact ventricular septum. AB - BACKGROUND: Pulmonary atresia and intact ventricular septum (PA-IVS) can be complicated by the presence of a severely hypoplastic thick-walled right ventricle with or without ventriculo-coronary arterial communications. A variable amount of myocardial pathology has been described in these hearts, probably the result of ischemic conditions and a high pressure in the right ventricle. We studied whether the capillary network is still intact, allowing a sufficient perfusion of the myocardium, which will be important for the success of palliative surgery. METHODS AND RESULTS: We studied the distribution of capillaries in the myocardium of hearts with PA-IVS and compared the results with normal hearts. The capillaries were detected by immunohistochemistry using a monoclonal antibody (408) against endothelium. Remarkable abnormalities in capillary distribution were found in the right ventricle of hearts with PA-IVS and reflect the arrangement of the myocytes. Thus, disorganization of capillaries, which is found to be the most common pattern, always paralleled the myocardial disarray. A low density of capillaries is always found in areas with a low density of myocytes, ie, with hypertrophied myocytes, compact fibrotic tissue, or diffuse fibrosis. Disarray and other disturbances in orientation of capillaries and myocytes are present in hearts with PA-IVS, a hypoplastic right ventricle, and ventriculo-coronary arterial communications. These disturbances are more extensive when interruptions of the coronary arteries are also present. In hearts with PA-IVS and a hypoplastic right ventricle only, extensive regions with low capillary densities and severe myocyte pathology are observed. On the contrary, hearts with PA-IVS and a normal-size right ventricle show minor abnormalities in capillary and myocyte organization. CONCLUSIONS: In hearts with PA-IVS, various abnormal capillary distribution patterns are found. Our findings correlate well with clinical data that reported the best surgical results in hearts in which the major part of the myocardium showed a normal capillary distribution and myocyte morphology. This suggests that the capillary distribution may be an important parameter for the function of the heart. Because the distribution of the capillaries is found to be a good reflection of the arrangement of the myocytes, antibody 408 is also a useful tool in detecting abnormalities of the myocardium in a fast and easy way. PMID- 7882490 TI - Ibutilide, a methanesulfonanilide antiarrhythmic, is a potent blocker of the rapidly activating delayed rectifier K+ current (IKr) in AT-1 cells. Concentration-, time-, voltage-, and use-dependent effects. AB - BACKGROUND: Ibutilide is an action potential-prolonging antiarrhythmic currently in clinical trials. The drug shares structural similarities with E-4031 and dofetilide, specific blockers of the rapidly activating delayed rectifier K+ current (IKr). However, previous in vitro studies in guinea pig myocytes have indicated that ibutilide does not block IKr but rather increases a slow inward sodium current. METHODS AND RESULTS: In this study, we compared the effects of ibutilide with those of dofetilide on outward current in mouse atrial tumor myocytes (AT-1 cells), a preparation in which, unlike guinea pig, a typical IKr is the major delayed rectifier and can be readily recorded in isolation from other currents. In AT-1 cells, ibutilide and dofetilide were both potent IKr blockers, with EC50 values of 20 (n = 12) and 12 (n = 8) nmol/L, respectively, at +20 mV. The time and voltage dependence of IKr inhibition by the two compounds were virtually identical. The following characteristics were most consistent with open channel block: (1) block increased with depolarizing pulses; (2) block increased with longer pulses; (3) currents deactivated more slowly in the presence of drug, resulting in a "crossover" typical of open channel block; and (4) with repetitive pulsing after drug wash-in, use-dependent block was observed. CONCLUSIONS: These data suggest that the clinical actions of ibutilide are mediated at least in part by block of IKr; an effect on inward currents is not excluded. AT-1 cells are a useful model system for the study of drug block of this important repolarizing current. PMID- 7882491 TI - Role of nitric oxide in the coronary microvascular responses to adenosine and increased metabolic demand. AB - BACKGROUND: The purpose of this study was to test the hypothesis that endothelium derived nitric oxide (NO) participates in coronary microvascular responses to adenosine and pacing-induced increases in metabolic demand by maintaining an optimal distribution of coronary resistance. METHODS AND RESULTS: Coronary microvascular diameters were measured by stroboscopic epi-illumination and intravital microscopy in open-chest dogs (n = 20). Epicardial coronary blood velocity (CBV) was measured by Doppler flowmetry. Responses to adenosine (1 and 10 micrograms.kg-1.min-1 IC) and left atrial pacing (180 beats per minute) were recorded before and after inhibition of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME, 30 micrograms.kg-1.min-1 IC). At baseline, adenosine dilated arterioles (< 100 microns) (11 +/- 4% and 25 +/- 3% diameter changes, P < .05) more than small arteries (> 100 microns) (-4 +/- 6% and 7 +/- 3%, P < .05 for the higher dose) and increased CBV (43 +/- 31% and 118 +/- 25%, P < .05). Left atrial pacing dilated arterioles (12 +/- 2%, P < .05) and small arteries (8 +/- 3%, P < .05) and also increased CBV (68 +/- 9%, P < .05). L-NAME abolished CBV increases caused by acetylcholine (10 and 100 ng.kg-1.min-1 IC; 53 +/- 33% and 168 +/- 82% versus -12 +/- 15% and -1 +/- 14%, P < .05) but not papaverine. Small arteries were constricted by L-NAME (-8 +/- 2%, P < .05), arterioles were dilated (10 +/- 4%, P < .05), and CBV was unchanged. After L-NAME, adenosine failed to dilate arterioles further (3 +/- 3% and 2 +/- 2%; P < .05 versus prior responses), and CBV changes were attenuated (14 +/- 16% and 8 +/- 13%; P < .05 versus prior responses). Pacing also failed to dilate arterioles (-4 +/- 2%, P < .05 versus prior response), resulting in an attenuated CBV change (34 +/- 13%, P < .05 versus prior response). The possibility that adenosine stimulates NO release in canine coronary arterioles was investigated in isolated arterioles (diameters, 81 +/- 4 microns; n = 8). Adenosine caused dose-dependent dilation to maximal diameter, which was unaffected by inhibition of NO synthesis by L-NAME. CONCLUSIONS: Inhibition of NO synthesis attenuates coronary dilation during adenosine infusions and during pacing-induced increases in metabolic demand. Inhibition of NO synthesis may shift the major site of coronary resistance into small arteries through autoregulatory adjustments in arterioles. These data therefore suggest that NO, by dilating predominantly small coronary arteries, promotes metabolic coronary dilation by preserving the tone and vasodilator reserve of arterioles. PMID- 7882492 TI - Myocardial high-energy phosphate and substrate metabolism in swine with moderate left ventricular hypertrophy. AB - BACKGROUND: Although left ventricular hypertrophy (LVH) is frequently associated with impaired coronary vasodilator reserve, it is uncertain whether this leads to myocardial ischemia under physiological conditions. The goal of the present study was to determine whether swine with moderate LVH exhibit metabolic evidence of ischemia when myocardial oxygen requirements are increased. METHODS AND RESULTS: Myocardial metabolism was evaluated in an open-chest anesthetized preparation at baseline and during dobutamine infusion in 13 adolescent pigs with moderate LVH induced by supravalvular aortic banding and 12 age-matched control pigs. Transmural myocardial blood flow was quantified with radioactive microspheres; the ratio of phosphocreatine to ATP (PCr/ATP) in the anterior LV free wall was measured by 31P-nuclear magnetic resonance; and anterior wall lactate release was quantified from the arterial-coronary venous difference in 14C- or 13C-labeled lactate. In a subset of 5 animals from each group, the metabolic fate of exogenous glucose was determined from the transmyocardial difference in 6-14C glucose and its metabolites 14C-lactate and 14CO2. Coronary reserve, as assessed by the ratio of blood flow during adenosine infusion to baseline blood flow, was significantly lower in the LVH pigs compared with controls (3.5 +/- 0.4 versus 5.5 +/- 0.4 mL/g.min, P < .05); however, transmural myocardial blood flow was similar in both groups of pigs, both at baseline and with dobutamine stimulation, probably reflecting the higher coronary perfusion pressure in the LVH pigs. At baseline, PCr/ATP tended to be lower in the LVH pigs (P = .09) but decreased similarly with dobutamine infusion in both groups. Isotopically measured anterior wall lactate release did not differ between the groups at baseline, nor did the increase in lactate release differ during dobutamine stimulation. The uptake of glucose, lactate, and free fatty acids did not differ between the groups in the basal state. However, during dobutamine stimulation, glucose uptake was greater in the LVH group (0.84 +/- 0.09 mumol/g.min versus 0.59 +/- 0.08 mumol/g.min, P < .05). In a subset of animals, 14C-glucose was used to assess glucose oxidation. These data showed that the LVH animals had a greater rate of glucose oxidation (0.6 +/- 0.10 versus 0.28 +/- 0.08 mumol/g.min, P < .05) and a greater rate of glucose conversion to lactate (0.20 +/- 0.04 versus 0.09 +/- 0.02 mumol/g.min, P < .05) compared with the control pigs. CONCLUSIONS: These results suggest that despite their reduced coronary vasodilator reserve and the absence of a greater rise in myocardial blood flow to compensate for a substantially higher LV double product, pigs with this model of moderate LVH do not exhibit a greater susceptibility to myocardial ischemia during dobutamine stress. However, LVH pigs exhibit significantly greater use of exogenous glucose during dobutamine stress, as evidenced by increases in both glucose oxidation and anaerobic glycolysis. PMID- 7882493 TI - Enalapril treatment increases cardiac performance and energy reserve via the creatine kinase reaction in myocardium of Syrian myopathic hamsters with advanced heart failure. AB - BACKGROUND: Converting enzyme inhibitor treatment of congestive heart failure slows progression to failure and reduces mortality rate. It is known whether these benefits are due solely to improved hemodynamics or also to improved myocyte energetics. This study examines the effect of enalapril treatment on both isovolumic contractile performance and its biochemical correlate, flux through the creatine kinase (CK) system, in an animal model of severely failing myocardium. METHODS AND RESULTS: Seven-month-old Syrian cardiomyopathic (TO-2 strain) and normal golden Syrian (FIB strain) hamsters were each randomly assigned to one of three groups supplied daily with either no, low (25 mg/kg body wt), or high (100 mg/kg body wt) doses of enalapril for 12 to 14 weeks. At 10 months of age, all substrates and products and flux through the CK reaction were measured in isolated perfused hearts by 31P magnetization transfer and chemical assay. Compared with normal hamsters, the myopathic hamsters exhibited significantly lower body weights and higher biventricular heart weights, which were partially reversed by drug treatment. The Langendorff-perfused hearts showed decreased isovolumic contractile performance with identical load conditions. This was partially reversed by drug treatment. In the failing hearts, the following substrate and product concentrations and enzyme activities were decreased compared with nonfailing hearts but were unchanged by drug treatment: ATP (-28%), phosphocreatine (-48%), free creatine (-64%), ADP (-51%), and CK (-34%, primarily MM isoenzyme). Flux through the CK reaction for the untreated cardiomyopathic hamster hearts was decreased by 67%, and this decrease was almost completely reversed by enalapril treatment. The increased CK flux is due to an increase in the rate constant for the reaction, since substrate concentrations are unchanged, and is not predicted by the rate equation. In enalapril-treated failing hearts, phosphoryl transfer via the CK reaction increased with contractile performance. This was not observed in the nonfailing hearts, in which energy reserve is adequate to support changes in contractile performance. CONCLUSIONS: Decreased flux through CK reaction leads to decreased capacity for ATP synthesis and may contribute to decreased contractile performance in cardiomyopathic hamster hearts. Enalapril treatment results in increased phosphoryl transfer through the CK reaction in failing myocardium, and this increase is coupled to improved cardiac performance. Decreased CK flux in failing hearts is due to a combination of decreased Vmax and lower guanidino pool; this mechanism fails to explain changes in CK flux in enalapril-treated failing hearts. PMID- 7882494 TI - Effects of pulmonary venous flow direction on mitral regurgitation jet area as imaged by color Doppler flow mapping. An in vitro study. AB - BACKGROUND: Although the effects of adjacent walls and left atrial pressure on mitral regurgitation (MR) jet area imaged by color Doppler have been examined, few data exist regarding the influence of pulmonary venous (PV) filling flow on regurgitant jets. Therefore, we designed a left atrial model to examine the relation between PV flow direction and MR jet area. METHODS AND RESULTS: The left atrial chamber (7.6 cm in diameter) was built with a PV inflow (1.0 cm in diameter) and mitral valve regurgitant orifice in the same plane. The MR jet was simulated as fixed in volume and velocity (3.5 m/s) and directed with a pulsatile pump into the left atrial model. PV flow with a constant velocity (30 cm/s) was driven by gravity (83 cm H2O). With left atrial mean pressure at either 10, 30, or 50 mm Hg, four flow patterns were examined: (1) PV flow away from the mitral valve, MR jet toward the pulmonary vein; (2) PV flow toward the mitral valve, MR jet toward the pulmonary vein; (3) PV flow away from the mitral valve, MR jet away from the pulmonary vein; and (4) PV flow toward the mitral valve, MR jet away from the pulmonary vein. MR color Doppler images were recorded with a 3.5 mHz frequency transducer and at 7-kHz pulse repetition frequency. For each condition, we compared jet area, length, and width of the MR signal. MR jet areas for conditions 3 and 4 were larger at 10 mm Hg than at 30 or 50 mm Hg left atrial pressure. Especially at the lower pressures, PV flow diminished the MR jet area in condition 4 compared with that in condition 3, such that MR jets were smaller in condition 4. In conditions 1 and 2, the jets were imaged at an oblique angle and were smaller than in conditions 3 and 4 (P < .001), but they were not significantly different from each other as imaged. CONCLUSIONS: In this model, factors including the direction of PV flow, the direction of MR as relates to the angle of interrogation, and the level of left atrial pressure influenced the size of MR jets. The effect of PV flow direction was diminished by increased left atrial pressure. PV flow directed away from the mitral valve was associated with larger MR jets than when PV flow was directed toward it (condition 4), probably because of jet distortion and flattening. PMID- 7882495 TI - New Gianturco-Grifka vascular occlusion device. Initial studies in a canine model. AB - BACKGROUND: Transcatheter closure of cardiovascular defects remains a challenge. Several occlusion devices are available, but each device has limitations. The purpose of this study was to evaluate the new Gianturco-Grifka vascular occlusion device (GGVOD) in a canine model. METHODS AND RESULTS: A total of 26 GGVODs were implanted as part of short- and long-term studies. In the short-term study, 1 GGVOD was implanted in each of 11 systemic arteries from 3.2 to 9.0 mm in diameter. All 11 arteries were occluded immediately. In the long-term study, an aortopulmonary shunt was placed in 10 dogs (9, Gore-tex graft; 1, subclavian artery) followed by GGVOD implantation; additionally, a GGVOD was implanted in 5 subclavian arteries. The dogs were boarded for 3 to 6 months, then recatheterized and euthanatized. Immediately after implantation, the 5 subclavian arteries and 9 Gore-tex shunts were occluded completely; the 1 subclavian artery shunt had a small residual leak. At recatheterization, all 10 shunts and 5 subclavian arteries were occluded completely. Necropsy revealed all shunts to be occluded, with the aortic and pulmonic orifices covered with a neointimal layer. The mean fluoroscopic time needed for GGVOD implantation was 9 minutes (range, 3 to 22 minutes). CONCLUSIONS: (1) In a canine model, the GGVOD is effective for transcatheter occlusion of arteries and aortopulmonary shunts from 3 to 9 mm in diameter. Possible indications in children include aortopulmonary collateral vessels, long patent ductus arteriosus, systemic-pulmonary shunts, AV malformations, and arteries supplying tumors. (2) GGVOD implantation requires a short fluoroscopic time. PMID- 7882496 TI - Cholesterol derivative of a new triantennary cluster galactoside lowers serum cholesterol levels and enhances secretion of bile acids in the rat. AB - BACKGROUND: Previous studies have demonstrated that cholesterol-derivatized galactosides exert a hypocholesterolemic effect by inducing hepatic uptake of atherogenic lipoproteins by means of galactose-recognizing receptors in the liver. However, a prolonged infusion of high concentrations of these compounds was required for this effect, possibly because of low affinity for the galactose recognizing asialoglycoprotein receptor on the parenchymal liver cell. METHODS AND RESULTS: We have designed a new series of triantennary galactosides to optimize the affinity and specificity for this receptor. The affinity of a triantennary galactoside for the asialoglycoprotein receptor appeared to be dramatically enhanced by proper spacing of the three terminal galactose groups. In rats, a single injection of N-[tris-O-(3,6,9-trioxaundecanyl-beta-D-galacto- pyranosyl)methoxymethyl]methyl-N alpha-[1-(6-(5-cholesten-3 beta- yloxy)glycyl)adipyl]glycinamide [TG(20A)C], the cholesterol derivative of the most selective galactoside, causes a dose-dependent decrease of < or = 45% in the serum cholesterol concentration (P < .001). This decrease is mainly attributed to a decrease in the level of serum HDL (P = .0066) and, to a lesser extent, serum LDL (P = .036). In addition, TG(20A)C strongly enhances the bile-acid secretion in rats during the first 2 hours after administration, which indicates that TG(20A)C-induced clearance of cholesterol from the bloodstream is efficiently coupled to hepatic bile-acid secretion. CONCLUSIONS: We conclude that TG(20A)C efficiently directs lipoproteins that contain cholesterol to the liver at a 30 fold-lower concentration than previously developed cholesterol-derived cluster galactosides. This newly developed approach to lower cholesterol levels may prove valuable for familial hypercholesterolemic patients or those with familial defective apolipoprotein B-100 who do not respond or who respond insufficiently, respectively, to conventional therapies. PMID- 7882497 TI - Evaluation of the postinfarct patient. PMID- 7882498 TI - Sex differences in mortality after myocardial infarction. Is there evidence for an increased risk for women? AB - BACKGROUND: A number of studies have indicated that women who have a myocardial infarction have higher mortality rates than men. The purpose of the present study was to review the literature on sex differences in mortality after myocardial infarction to determine whether female sex is independently associated with lower survival. METHODS AND RESULTS: Reports were identified mainly through a MEDLINE search of the English-language literature from January 1966 through June 1994. Studies included were those comparing mortality after myocardial infarction between men and women, controlling at least for age and with more than 30 outcome events. After duplicate patient series were eliminated, 27 reports were included in our review. Crude rates were higher in women than in men during the early phase (in-hospital or first month), but control for age alone or in combination with other factors reduced sex differences in almost all studies. Unadjusted mortality rates among the survivors of the early phase were similar for men and women in most studies, and control for age and other factors resulted in an increased survival rate in women compared with men in several investigations, particularly those with a follow-up of > 1 year. CONCLUSIONS: Much of the increased early mortality after myocardial infarction in women is explained by the older age and more unfavorable risk characteristics of the women. In the long run, when differences in age and other risk factors are controlled for, women tend to have an improved survival compared with men. PMID- 7882499 TI - Role of neutrophils in myocardial ischemia and reperfusion. AB - In the intact organism, ischemic myocardial injury initiates an acute inflammatory response in which polymorphonuclear leukocytes (PMNs) are major participants. Evidence indicates that the interplaying inflammatory reactions are augmented by reperfusion and that accumulating PMNs can contribute to myocardial damage, eg, by release of oxygen-derived free radicals, proteases, and leukotrienes. In experimental models, interventions aimed at PMN inhibition can exert cardioprotective effects, and some of these strategies raise hope for future clinical applications. A greater understanding of the mechanisms involved in PMN-mediated myocardial damage is necessary for designing a rational approach to reduce the putative detrimental effects of PMNs without antagonizing their favorable consequences in tissue healing. PMID- 7882500 TI - Images in cardiovascular medicine. Acute myocarditis masquerading as acute myocardial infarction. PMID- 7882501 TI - Angiotensin-converting enzyme and lipoprotein(a) as risk factors for myocardial infarction. PMID- 7882502 TI - Who was thrombogenic: the stent or the doctor? PMID- 7882503 TI - Different roads to the assessment of myocardial viability. Lessons from PET for SPECT. PMID- 7882504 TI - CD-4 lymphopenia induced by streptokinase. PMID- 7882505 TI - Sudden cardiac death in heart failure: the role of abnormal repolarization. PMID- 7882506 TI - Enzymes as antigens in autoimmune endocrinopathies. PMID- 7882507 TI - Homocysteine species as components of plasma redox thiol status. PMID- 7882508 TI - Clinical utility of biochemical analysis of cerebrospinal fluid. AB - In addition to microbial culture, cytology, and immunological studies, physicians rely on the clinical chemistry laboratory for biochemical analysis of patients' cerebrospinal fluid (CSF). However, apart from routine glucose and protein determinations, the clinical value of other CSF analytes is often unclear. Here, we review the literature pertaining to the use of CSF biochemical measurements in managing patients with infectious disease, neoplasia, stroke and trauma, and dementia. Although a small number of studies demonstrate potential usefulness of some markers, we conclude that, without further study, the data are insufficient to support the routine clinical use of most of the analytes examined. PMID- 7882509 TI - Effect of thiol oxidation and thiol export from erythrocytes on determination of redox status of homocysteine and other thiols in plasma from healthy subjects and patients with cerebral infarction. AB - Changes in concentration of reduced and oxidized low-M(r) thiols were measured in blood and plasma before and after the separation of blood cells. If centrifugation of blood was postponed, the reduced form of homocysteine in plasma increased with time at 22 degrees C; in contrast, the concentrations of other reduced thiols (cysteine, glutathione, and cysteinylglycine) decreased. In plasma the reduced forms of all thiols disappeared at a rate that followed first-order kinetics. The rates of disappearance ("half-lives") were temperature-dependent; they were about the same for glutathione and homocysteine (11.7 and 14.3 min, respectively, at 22 degrees C) and somewhat higher for cysteinylglycine and cysteine. After establishing proper sampling conditions for reduced thiols, we measured this thiol fraction as well as free (non-protein-bound) and total thiols in 10 reference subjects and 19 patients with cerebral infarction. Mild but significant hyperhomocysteinemia involving total and free homocysteine (but not reduced homocysteine) was found in the patients. PMID- 7882510 TI - Interlaboratory/intermethod differences in functional sensitivity of immunometric assays of thyrotropin (TSH) and impact on reliability of measurement of subnormal concentrations of TSH. AB - Clinically relevant interassay precision profiles for thyrotropin (thyroid stimulating hormone; TSH) were constructed with human serum pools measured over 4 8 weeks by six immunometric assays, in at least two different reagent lots. Functional sensitivities (the concentration at which the interassay CV is < or = 20%) were determined in four to eight clinical laboratories plus the respective manufacturer's laboratory. These studies revealed that the manufacturer's stated functional sensitivity limit is rarely duplicated in clinical practice. Loss of specificity (indicated by artifactually high values) was seen with some methods when used to measure certain unrefrigerated low-TSH sera. Measurement of TSH in four human serum pools (TSH < 0.05-0.25 mIU/L) by 16 different methods (each in at least eight UK or US laboratories) showed that some methods could not reliably distinguish subnormal from normal TSH values. Better pool rankings and fewer misclassifications of low-TSH sera as "normal" were seen with use of assays capable of "third-generation" functional sensitivity (0.01-0.02 mIU/L) than with assays with "second-generation" functional sensitivity (0.1-0.2 mIU/L). Because inter- and intramethod differences in functional sensitivity negatively impact the diagnostic accuracy and cost-effectiveness of a TSH-centered thyroid-testing strategy, laboratories should independently establish an assay's functional sensitivity by a clinically relevant protocol. Moreover, manufacturers should assess functional sensitivity more realistically and improve the robustness of assays to ensure that their performance potential is consistently met in clinical practice. PMID- 7882511 TI - Immunoprecipitation assay for autoantibodies to steroid 21-hydroxylase in autoimmune adrenal diseases. AB - Adrenal autoantibodies characteristic of autoimmune Addison disease are directed towards steroid 21-hydroxylase (21-OH; EC 1.14.99.10). We describe a new assay to measure 21-OH autoantibodies (21-OH Abs), based on immunoprecipitation by the antibodies of 35S-labeled human 21-OH. Using this immunoprecipitation assay (IPA), we detected 21-OH Abs in 42 of 64 (66%) patients with Addison disease and in 14 of 19 (74%) patients with autoimmune polyendocrine syndromes type I and type II. No 21-OH Abs were detected by the IPA in any patients with Addison disease attributable to tuberculosis (n = 9) or adrenoleukodystrophy (n = 9) or in patients with autoimmune thyroid disease (n = 28), systemic lupus erythematosus (n = 10), myasthenia gravis (n = 10), rheumatoid arthritis (n = 10), or insulin-dependent diabetes mellitus (n = 12). None of the 26 sera from healthy normal blood donors was positive for 21-OH Abs by the assay. We found good agreement between 21-OH Abs measured by IPA and by Western blotting (r = 0.83, n = 123, P < 0.001). The inter- and intraassay CVs for IPA were well < 10% at high, medium, and low concentrations of 21-OH Abs. Overall, our studies indicate that the IPA provides a specific, sensitive, and convenient system for measuring 21-OH Abs. PMID- 7882512 TI - Direct enzyme-linked immunosorbent assay and a radioimmunoassay for melatonin compared. AB - A novel commercially available ELISA for direct measurement of melatonin concentration in serum was evaluated and compared with an RIA routinely used in our laboratory. The direct ELISA is technically simpler, requires a smaller sample volume (0.1 mL), and compares well with RIA in terms of stability of the calibration curve and intra- and interassay CVs. Correlation with RIA measurements is, however, suboptimal (y = 0.39x + 56; r = 0.65, P < 0.001; n = 138), which may be due to a serum effect, as evidenced by dilution studies. Furthermore, the detection range of the ELISA does not cover the physiological daytime melatonin concentrations in humans. Adding an extraction and 10-fold concentration step shifted the detection range of the ELISA to include low physiological concentrations as well. Correlation with RIA measurements also improved significantly (y = 0.97x-23; r = 0.95, P < 0.001; n = 105), probably due to removal of the serum effect. Although extraction increases the required sample volume (1.5 mL), work load, and procedure time, this step is necessary for the ELISA to compete successfully with RIA. PMID- 7882513 TI - HPLC measurement, blood distribution, and pharmacokinetics of oral clotrimazole, potentially useful antisickling agent. AB - Clotrimazole (CLT) has recently been shown to be a potent and specific inhibitor of the Ca(2+)-activated K+ channel and to thereby prevent K+ loss and cellular dehydration of sickled erythrocytes. This evidence suggests that oral CLT may be a useful new therapy for sickle cell disease. Here, we describe the development of an HPLC assay to measure CLT, a method we used to study the pharmacokinetics and transport of CLT in normal volunteers. The assay's linear range extended to 10 mumol/L; the detection limit was 0.1 mumol/L, analytical recovery 97.7%, and run-to-run imprecision (CV) < 4.7%. In unaffected subjects, CLT concentration peaked within 6 h of oral administration and returned to close to baseline by 24 h. High-density lipoproteins appear to be the main carriers of this drug in both normo- and hypertriglyceridemic plasma. We conclude that the method described here is ideally suited for therapeutic monitoring of CLT concentrations. PMID- 7882514 TI - Effect of storage at 4 degrees C and -20 degrees C on lipid, lipoprotein, and apolipoprotein concentrations. AB - We have investigated the effects on lipid, apolipoprotein, and lipoprotein measurements of storing unfractionated serum at 4 degrees C for 10 days and at 20 degrees C for 10 days or 3 months. Total serum concentrations of lipids were stable, although apolipoprotein B showed a 5.3% increase after 3 months at -20 degrees C (P < 0.001). Increases in low-density (LDL) and high-density lipoprotein (HDL) triglyceride and very-low-density lipoprotein (VLDL) esterified cholesterol concentrations and decreases in free cholesterol concentrations in LDL and HDL after storage of serum for 10 days at 4 degrees C were verified by fractionation of lipoproteins by sequential flotation ultracentrifugation. Ten days' storage of serum at -20 degrees C resulted in increases in VLDL triglyceride and phospholipid concentrations, with decreases in HDL concentrations in triglycerides and phospholipids; changes were more extensive after 3 months at -20 degrees C. We conclude that ultracentrifugation of serum for lipoprotein analysis should be performed as soon as possible after collection. PMID- 7882515 TI - Isotope dilution mass spectrometry as a candidate definitive method for determining total glycerides and triglycerides in serum. AB - A new isotope dilution mass spectrometric method for total glycerides and triglycerides in human serum is described. Total glycerides are defined as the sum of tri-, di-, and monoglycerides plus free glycerol; triglycerides are defined as the pure triglyceride species. In both determinations, serum samples are supplemented by addition of [13C3]tripalmitin, processed, derivatized, and the abundance ratios of selected ions are determined. Bias is investigated by quantifying the analyte in the same samples under different chromatographic and ionization conditions. The analytes were determined in two human serum pools. The CV for a single measurement ranged from 0.35% to 0.72%, and the relative SEM ranged from 0.10% to 0.34%; there was no significant bias in the measurements. The combination of high precision and absence of significant bias in the results qualify this method for consideration as a Definitive Method as defined by the National Committee for Clinical Laboratory Standards. PMID- 7882516 TI - Measurement and physiological significance of lipoprotein and hepatic lipase activities in preheparin plasma. AB - A radiochemical method for selective measurement of postheparin lipase activities was adapted to analyze lipoprotein lipase and hepatic lipase in preheparin plasma. The assay sensitivity was increased about four-fold by doubling both the volume of plasma used and the volume of lipolytic products taken for liquid scintillation counting, and was further improved by increasing the incubation period by 50% to 90 min. Rabbit antiserum to human hepatic lipase was unsuitable for the selective measurement of lipoprotein lipase because of apparent endogenous lipolytic activity. Preheparin hepatic lipase, however, was sensitive to inactivation by sodium dodecyl sulfate (SDS), the inhibition being greatest (> 90%) for plasma incubated with an equal volume of 40 mmol/L SDS. Intra- and interassay CVs for the two enzymes were 12.5-14.6% and 17.4-19.7%, respectively. In a cross-sectional study of 84 healthy subjects, pre- and postheparin hepatic lipase activities were higher in men than women, were correlated with indices of obesity, and were significantly correlated with one another, which explained the association of the former with plasma concentrations of high-density lipoprotein (HDL), HDL2, and small, dense low-density lipoproteins. There was no significant relationship between pre- and postheparin lipoprotein lipase activities, but the former were correlated with plasma concentrations of free fatty acids (FFA) and very-low-density lipoprotein. Apparently, preheparin activities of hepatic lipase, but not of lipoprotein lipase, may be a useful measure of the physiological function of "whole body" enzyme activity in cross-sectional and metabolic studies, where heparinization is not possible. Preheparin lipoprotein lipase activities, however, may reflect displacement of the enzyme by FFA and subsequent binding to remnants of triglyceride-rich lipoproteins. PMID- 7882517 TI - Robust nonradioactive oligonucleotide ligation assay to detect a common point mutation in the CYP2D6 gene causing abnormal drug metabolism. AB - A new nonradioactive oligonucleotide ligation assay for the detection of a common point mutation in the CYP2D6 gene is presented. The assay takes advantage of simultaneous time-resolved fluorescence measurements of lanthanide-labeled probes and the specificity of T4-DNA ligase in combination with the polymerase chain reaction. This strategy makes it possible to perform the assay using both the wild-type-specific and mutant-specific probes simultaneously, securing an internal control in each reaction. We show that the allele-specific ligation part of the assay can be performed with great accuracy over a wide range of temperatures, salt concentrations, and T4-DNA ligase concentrations. This eliminates the risk of false-positive or false-negative reactions due to variations in these factors. Because the assay is simple to perform, is very reliable, and can be partly automated, we conclude that it is well-suited for analysis in a routine laboratory. PMID- 7882518 TI - Mutation screening of the codon 3500 region of the apolipoprotein B gene by denaturing gradient-gel electrophoresis. AB - Familial defective apolipoprotein B (FDB) is a clinical condition resembling familial hypercholesterolemia. The underlying genetic defects are mutations in the apolipoprotein B-100 (apo B-100) gene. Two mutations (Arg3500 --> Gln and Arg3531 --> Cys) are known to date. We designed a denaturing gradient-gel electrophoresis (DGGE) technique to detect sequence variations in codons 3456 3553 of the apo B-100 gene. In 46 heterozygous FDB patients with the predominant codon 3500 mutation, a uniform four-band DGGE pattern was seen, whereas 57 non FDB patients showed the uniform single-band pattern expected in normal homozygotes. The recently described codon 3531 mutation and a previously unpublished Arg --> Pro mutation in codon 3480 showed unique DGGE patterns, allowing unambiguous differentiation of the three mutations. The DGGE method thus both detects known FDB mutations and screens for other mutations in codons 3456 3553 of the low-density lipoprotein receptor binding region of apo B-100; it can be used as a first-line screening method for FDB. PMID- 7882519 TI - Determination of alpha-amylase activity: methods comparison and commutability study of several control materials. AB - Six different methods for alpha-amylase determination were compared by assaying human serum samples covering a wide range of alpha-amylase values. All the methods studied use as substrate a maltooligosaccharide with a chromophore group at the reducing end; some are chemically blocked at the nonreducing end. Intermethod comparison by regression and correspondence analyses showed significant differences for two methods. The commutability of 12 commercial control materials containing alpha-amylase was also assessed by the different methods in comparison with human serum specimens containing the pancreatic and salivary isoenzymes. We also studied the behavior of pancreatic and salivary materials prepared in our laboratory. Control materials with alpha-amylase of non human origin were not commutable with the enzyme in human sera and should not be used for intermethod calibration. PMID- 7882520 TI - International normalized ratio for prothrombin times in patients taking oral anticoagulants: critical difference and probability of significant change in consecutive measurements. AB - To determine when a change in serial measurements of prothrombin time in patients receiving oral anticoagulant therapy (ACT) is a statistically significant biological change necessitating dose adjustment, one must know the size of the "critical difference" in statistical terms (i.e., probabilities). In a cohort of 32 ACT patients at pharmacological steady-state, we studied the within-subject total variation of prothrombin time, expressed as International Normalized Ratio (INR), over 6 months. The total within-subject variation (CV) of INR was 10.1%. The corresponding critical differences required for significance of change in serial INR results was 0.7 at a therapeutic target of 2.5 INR and 1.0 at a therapeutic target of 3.5 INR. The data presented allow generation of objective criteria for monitoring ACT patients and deciding dose adjustments. We recommend that estimations of critical differences for significant change of INR in ACT patients should be based on results obtained in the specific clinic investigated to mirror the routine total variation of INR measurements they obtain. PMID- 7882521 TI - HPLC with o-phthalaldehyde precolumn derivatization to measure total, oxidized, and protein-bound glutathione in blood, plasma, and tissue. AB - This HPLC assay with o-phthalaldehyde precolumn derivatization is used to measure the total, oxidized, and protein-bound forms of glutathione in human blood, plasma, and rat tissue. Total glutathione (i.e., sum of reduced, oxidized, and protein-bound fractions) was determined after reduction with dithiothreitol and protein precipitation with perchloric acid (PCA). A preliminary selective blockage of free sulfhydryl groups with N-ethylmaleimide was necessary to evaluate the different oxidized forms. The assay showed high sensitivity (< 0.05 pmol injected) and good precision (within-day CVs of 5.5% to 6.4%), recovery (101% +/- 4%), and linearity (r > 0.999). Samples, after PCA acidification, were stable at room temperature and 4 degrees C for 3 days, and at -20 degrees C and 80 degrees C for > 1 month. The method (involving automated derivatization) not only is very rapid and simple but also allows immediate processing of many different biological samples. PMID- 7882522 TI - Catecholamine interference with enzymatic determination of nonesterified fatty acids in two commercially available test kits. AB - We present evidence that catecholamines, which are commonly used to stimulate lipolysis in adipose tissue in vitro, interfere with the enzymatic determination of non-esterified fatty acid (NEFA) in two commercially available kits. Measurement of a 100 mumol/L standard with the Wako "NEFA C" test kit was 60% inhibited by 100 mumol/L norepinephrine and was completely inhibited by 100 mumol/L isoproterenol or by 1 mmol/L norepinephrine or epinephrine. Measurement with the Boehringer Mannheim "Free Fatty acids, Half-micro test" was completely inhibited by 100 mumol/L norepinephrine and was also affected by concentrations as low as 0.1 mumol/L. We propose that this effect is due to the catecholamines interfering with a step common to the two kits, the generation of hydrogen peroxide and oxidation of a chromagen; furthermore, this interference appears to be stoichiometric. We also give details of an alternative in-house method, which does not depend on the generation of hydrogen peroxide and is not affected by catecholamines. PMID- 7882523 TI - Decreased amino acid uptake by erythrocytes during postoperative sepsis. AB - We describe a patient with postoperative sepsis associated with reduced ability to transport amino acids into erythrocytes. Administration of amino acid infusion showed no effect on plasma or red blood cell concentrations of the amino acids during the sepsis period. However, when the site of sepsis was removed, patient recovery was associated with marked increases of all amino acids, particularly in the red blood cells. The case illustrates the potential of red blood cells as a marker of amino acid utilization and demonstrates the association of sepsis with effects on cellular uptake. PMID- 7882524 TI - Stability of free amino acids in sulfosalicylic filtrates. PMID- 7882525 TI - Two fluorescence polarization immunoassays for total thyroxine and T-uptake quantification. PMID- 7882526 TI - Interleukin-6 and C-reactive protein during pediatric cardiopulmonary bypass. PMID- 7882527 TI - Blood collection and analytical considerations in blood lead screening in children. PMID- 7882528 TI - Laboratory test scores to aid identification of primary nonfunction of liver transplants. PMID- 7882529 TI - Glycosylation of alpha 1-acid glycoprotein in bacterial lung infections: distinct pattern in tuberculosis. PMID- 7882530 TI - Lipid and thyroid changes after partial thyroidectomy: guidelines for L-thyroxine therapy? PMID- 7882531 TI - Functional sensitivity of thyrotropin assays. PMID- 7882532 TI - Factitious additional band simulating Bence Jones protein caused by contamination from face plate for ureterostomy. PMID- 7882533 TI - In situ PCR amplification of Guthrie card DNA to detect cystic fibrosis mutations. PMID- 7882534 TI - Flow cytometry to overcome interferences in impedance-based leukocyte counting. PMID- 7882535 TI - Negative interference in immunoassays. PMID- 7882536 TI - Microsatellite instability in cancer identified by non-gel sieving capillary electrophoresis. PMID- 7882537 TI - Blood sample tubes for lactate assay. PMID- 7882538 TI - Toward unraveling the heterogeneity of high-density lipoproteins with a functional approach. PMID- 7882539 TI - The phenomenon of travelling waves: a review. AB - As early as 1934 evidence appeared in animals that waves of activity do not always remain stationary but can actually spread over the whole cortex. In the next year some of the earliest studies on the EEG of man showed phase changes of alpha activity that could account for the TW, which later was described when apparatus was built to better view it, especially in the 1950s. The TW has been described mainly as alpha activity that appears to travel both in abnormal and also normal conditions, including the resting state. The phenomenon seems to be enhanced with either external stimuli or endogenous emotional states, which increase phase changes on different brain areas. The travel has been described in all directions from the frontal to the occipital pole, and early work suggests that the posterior-anterior direction may be more often found in abnormal mental states. The speed of travelling over the scalp has varied usually from 1-20 m/sec, but generally has been reported around 5 m/sec. Most investigators have reported that the positive phase is the one which most clearly travels. In exploring the phenomenon of the travelling wave, it is clear that maximal positivity and negativity of the alpha is not always on the occipital regions, as many clinical studies would imply; instead, the fronto-central areas in particular are often the focus of maximal alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882540 TI - Multifocal independent Spike syndrome: relationship to hypsarrhythmia and the slow spike-wave (Lennox-Gastaut) syndrome. AB - During a 3 year period EEGs were performed in 64 children with multifocal independent spikes (MIS), 17 with slow spike-wave complexes (SSWC), 22 with MIS and SSWC and 15 with hypsarrhythmia. Only EEG records containing adequate wakefulness and sleep were analyzed in 40 children with two or more serial EEGs at least 5 months apart. Transitions from one pattern to another occurred in 25/40 patients, consistent in all cases with the following sequence: Hypsarrythmia-->MIS-->MIS and generalized discharges-->SSWC. Patients with and without transitions did not differ in their age at presentation or duration of follow-up. Eleven of 12 patients whose initial EEG showed hypsarrhythmia or multifocal independent spikes underwent transitions, compared to 0/8 patients with SSWC (p < 0.001), indicating that SSWC is a stable pattern in children. Over a 6 month period, we also prospectively analyzed EEGs of 20 patients with multifocal spikes, hypsarrhythmia, and slow spike-wave complexes. Sleep activated additional spike foci, increased the frequency of generalized spike discharges and produced synchronization of bitemporal and bifrontal spike-wave discharges at 1.5-2.5 Hz the same as SSWC. PMID- 7882541 TI - Spectral coherence in normal adults: unrestricted principal components analysis; relation of factors to age, gender, and neuropsychologic data. AB - This paper demonstrates, by means of Principal Components Analysis (PCA), an objective approach to the reduction of large data sets produced by multichannel spectral coherence analyses. Coherence data, gathered from 371 normal healthy adults using Hjorth/Laplacian referencing during waking eyes-open and eyes-closed states, were analyzed by "unrestricted" PCA where neither spatial nor temporal variance was folded into among subject variance. There was substantial data reduction with our 4416 initial coherence variables for each state reduced to just 150 factors containing approximately 80% of the variance reflecting a 30 fold concentration of information content. Varimax rotation of the first 40 factors, encompassing 50% of the total variance for both states, revealed loading patterns primarily bilateral with no hemispheric bias, relationships primarily between distant single electrode pairs, (although a single electrode to multiple electrode pattern was also observed), and involvement of all spectral bands. Elemental left to right and anterior to posterior coherence patterns, often used on an a priori basis for coherence studies, were not evident among the rotated factor loading patterns. On the basis of high loadings upon extra bipolar artifact channels, 32 factors accounting for approximately 40% of the variance were identified as reflecting artifactual coherence relationships. By multiple regression the 48 non-artifactual factor scores successfully predicted subject age. In general, coherence diminished with age, which may partly explain age related EEG desynchronization in healthy adults. Coherence factors also predicted 6 of 10 neuropsychologic variables. Gender was successfully predicted by discriminant analysis. No global interpretations about coherence and gender or neuropsychologic function were possible, i.e., almost equal numbers of factors increased as decreased in males as females. PCA derived coherence factor scores are useful for subsequent statistical analyses, but their factor loading plots of cortical coupling may require more experience to fully interpret. PMID- 7882542 TI - Relationships between EEG coherence and neuropsychological tests in dementia. AB - Previous research has demonstrated differences in resting state EEG coherence among groups of subjects with dementia of the Alzheimer type (DAT), multi-infarct dementia (MID), and normal elderly controls. Since reduced coherence between brain sites has been thought to reflect functional disconnection between brain areas, we hypothesized that decreased coherence would be associated with cognitive dysfunction as assessed by neuropsychological tests. We correlated several neuropsychological tests with four coherence variables and found that reduced coherence was associated with impairment on specific neuropsychological tests in ways that conform to and supplement current knowledge about the localization of brain functions. The results are consistent with the hypothesis that coherence reflects a functional breakdown in communication between brain areas, and that coherence may be a more precise way to localize brain function than other EEG variables. PMID- 7882543 TI - Clinical electroencephalograms in patients with catatonic disorders. AB - Catatonia is a neuropsychiatric syndrome of motor signs most frequently found in affective disorders and schizophrenia. Catatonic disorder due to a general medical condition has been added to the DSM-IV nosology. Laboratory studies, such as electroencephalography (EEG) may assist in the differential diagnosis of catatonic disorders. Twenty-six patients hospitalized on a general psychiatric unit or medical psychiatric unit received electroencephalograms (EEGs) as part of their routine care. Clinical EEG abnormalities were reported in 17 of these patients. The presence of abnormalities was associated with age greater than 40, diagnosis of neuroleptic malignant syndrome and the presence of general medical conditions associated with the development of catatonia. Although no specific EEG patterns were associated with catatonic disorder due to general medical conditions, these findings suggest that the EEG is an important tool in the evaluation of patients presenting with catatonia. PMID- 7882544 TI - Somatosensory evoked potentials in acute migraine with sensory aura. AB - One current view of migraine pathophysiology suggests that vasospasm causes cerebral ischemia and focal symptoms during an aura and that reactive hyperemia accompanies the headaches. Eight patients with acute migraine with sensory aura were studied with somatosensory evoked potential (SEP) to examine the vascular theory of acute migraine headache. All patients had sudden onset of hemiparesthesia as an aura followed by throbbing headaches. SEPs were obtained from the median nerve stimulation in two patients during the aura phase and six during the headache phase. SEPs were abnormal in both cases during the aura phase. The abnormality consisted of attenuation of amplitude and prolongation of N19 in the sensory cortex, resulting in prolongation of central conduction time, which gradually returned to normal during the headache phase. SEPs of six other patients obtained during the headache phase were also normal. The study concludes that: (1) there is a different pathophysiology between aura and headache phase; (2) the changes of SEPs during the aura may result from cerebral ischemia; and (3) normal SEPs during the headache phase suggest that reactive hyperemia may not alter SEP wave forms. PMID- 7882545 TI - Characteristics of travelling waves under various conditions. AB - In this mapping study, the goal was to investigate in 10 subjects the phenomenon of the travelling waves (TW), especially of alpha activity, under conditions of (1) rest, (2) calculations, (3) emotional experience and (4) pain. The TW during wakefulness usually arose from the areas with the highest amplitude of alpha, called major peaks, for both positive (pos.) and negative (neg.) polarities. These areas were Pz (pos. and neg.) at rest, O2 (pos.) and Pz (neg.) during calculation, O1 (pos.) and O2 (neg.) during emotion and T6 (pos.) and O1 (neg.) during pain. When differences were determined between the latter 3 conditions and the resting state, a focal event-related desynchronization (ERD) became evident on T5 during math, on Pz during emotion and on both CP areas during pain. Surrounding the areas of ERD were areas of event-related synchronization (ERS). The TW were related to phase differences between the different electrode locations, seen more frequently with the pos. polarity, and more often with emotion or calculation. The direction of the TW was most often toward the midline during rest, from the right to midline (calculation), from the left to midline (emotion) and from the midline to the left (pain). Changes on one side of the head were often associated with opposite types of changes on the other side. Sleep spindles were also analyzed showing the major peaks on Fz and F4 with pos. polarities often seen anteriorly and neg. polarities posteriorly. TW were also seen with spindles, more often with the positive polarity. The direction was usually from the midline for the positive polarity and toward the midline for the neg. phase. The phenomenon of the TW is discussed, especially its possible neurophysiological significance as a means of transmitting information throughout the brain. PMID- 7882546 TI - Can we prevent colorectal cancer? PMID- 7882547 TI - Sulindac therapy of colorectal polyps in familial adenomatous polyposis. AB - Familial adenomatous polyposis (FAP) is characterized by multiple adenomatous colorectal polyps, some of which progress to adenocarcinoma in the absence of surgery. Colectomy with ileorectal anastomosis still remains much in use, although strict surveillance of the rectal stump is necessary to prevent rectal cancer. After 1983, sulindac has been used to control rectal polyps in about 90 FAP patients, at doses of 150-400 mg/day. The treatment was well tolerated, and regression of the polyps was frequently observed. However, recurrence of polyps was sometimes observed, and the onset of rectal cancer during sulindac therapy was also reported. A review of the literature and the personal experience of the authors are here presented, discussing the pharmacological profile and possible mechanisms of action of sulindac. PMID- 7882548 TI - Alcohol and the risk of cancers of the stomach and colon-rectum. AB - Alcohol drinking is strongly related to cancer of the upper digestive tract, but the pattern of risk with alcohol drinking is clearly different for cancer of the stomach and colon-rectum. All twelve cohort studies and three-quarters of 40 case control investigations on the topic weigh against the possibility of a substantial effect of alcohol consumption on the risk of stomach cancer. Evidence is still insufficient to establish whether cancer of the cardiac region of the stomach is related to alcohol intake to any different extent than the rest of the stomach. With reference to colorectal cancer, different types of epidemiological studies are consistent in suggesting some direct relations with alcohol drinking. The association, however, is moderate, and an elevated risk of a factor 2--or even of a factor 1.5--for both cancers of the colon and rectum can now be excluded even for the highest levels of alcohol consumption. PMID- 7882549 TI - Cytokines (immunoinflammatory hormones) and their natural regulation in inflammatory bowel disease (Crohn's disease and ulcerative colitis): a review. AB - Cytokines, particularly the proinflammatory cytokines, whose role and natural regulation in inflammatory bowel disease are reviewed here, are produced by many cell types, including immune cells. Cytokines function as important hormones of the immune system, and many act both regionally and systemically via specific receptors. The demonstration of increased circulating and mucosal levels of proinflammatory (and other) cytokines (and receptors) in active inflammatory bowel disease does not by itself constitute any proof as to the primary involvement of these mediators. However, they may contribute significantly to disease manifestations, and specific therapeutic intervention at the cytokine or cytokine receptor level may show up to be clinically most relevant. This is underscored by the increasing evidence that proven therapies of inflammatory bowel disease to a great extent seem to function through cytokine modulation. PMID- 7882550 TI - Colitis cystica profunda: self-inflicted by rectal trauma? Report of a case. AB - Colitis cystica profunda (CCP) is a rare benign condition with a controversial etiology. We report a case of CCP in a patient with a history of anal masturbation, supporting an acquired traumatic etiology. Diagnosis was assisted by transrectal ultrasound. The patient was successfully treated by local excision. PMID- 7882551 TI - The molecular basis for a polyspecific antibody. PMID- 7882552 TI - Anti-La (SS-B) but not anti-Ro52 (SS-A) antibodies cross-react with laminin--a role in the pathogenesis of congenital heart block? AB - Cross-reactions between maternally derived autoantibodies and fetal cardiac antigens have been postulated to play a role in the pathogenesis of congenital heart block (CHB). We have explored the cross-reactivity of autoantibodies to the small ribonuclear autoantigens, La/SS-B and Ro/SS-A, with laminin, the major component of cardiac sarcolemmal membrane using affinity-purified antibodies from patients with Sjogren's syndrome (SS). Anti-La antibodies purified from eight of 10 patients cross-reacted significantly with mouse laminin by ELISA. In contrast, purified antibodies to Ro52 from the same 10 patients showed little or no binding to laminin. Laminin inhibited up to 70% binding of anti-La antibodies to La antigen, and La inhibited up to 65% binding of anti-La antibodies to laminin. The cross-reaction was further examined on cryosections of 10 human fetal hearts aged from 8.7 to 14.9 weeks of gestation, two normal adult hearts, and one pathological adult heart with a diagnosis of dilated cardiomyopathy. Anti-Ro52 antibodies did not bind to the surface of cardiac cells. However, anti-La antibodies from seven of 10 patients tested bound to the surface of fetal myocytes from hearts aged 9.4 to 14.9 weeks of gestation, and also to the myocytes from the pathological adult heart but not to normal adult hearts. Preincubation with La antigen abolished the binding of anti-La antibodies to the surface of adult heart myocytes with dilated cardiomyopathy, and pre-incubation with mouse laminin could partially block this binding. These results suggest that molecular mimicry between laminin and La, but not Ro52, may act as a target for specific maternal autoantibodies, and contribute to the pathogenesis of CHB at a critical stage during fetal cardiac development. PMID- 7882554 TI - Expression of endogenous retroviruses, ERV3 and lambda 4-1, in synovial tissues from patients with rheumatoid arthritis. AB - We addressed the question of whether or not expression of human endogenous retroviruses (ERV), ERV3 and lambda 4-1, is related to the pathogenesis of rheumatoid arthritis (RA). In genomic Southern hybridization, there were no significant differences between RA patients and healthy volunteers with regard to frequencies of restriction fragment length polymorphism (RFLP) patterns, for either ERV3 or lambda 4-1. By Northern blot analysis using fresh synovial tissues, cultured synovial cells, and peripheral blood mononuclear cells (PBMC) from patients with RA, we noted two molecular species of ERV3 mRNAs of 3.5 kb and 9.0 kb sizes, and one single molecular species of lambda 4-1 mRNAs of 4.2 kb size. The expression was detected not only in RA patients but also in synovial cells from osteoarthritis (OA) as a non-RA control and PBMC from healthy volunteers, and was not related to RA activities or treatments. Although ERV3 and lambda 4-1 expression may not be directly associated with the pathogenic pathway of RA, the possibility exists that human ERV may have a causative role in autoimmune diseases, including RA. We also examined the effect of cytokines on the transcriptional regulation of ERV3. Although the level of ERV3 expression in cultured synovial cells did not change with IL-1 beta treatment, the level for cultured proximal tubular epithelial cells (hKEC) was up-regulated. PMID- 7882553 TI - Analysis of proteins that interact with the IL-2 regulatory region in patients with rheumatic diseases. AB - In order to investigate transcriptional regulation of lymphokine genes in rheumatic diseases, peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) were analysed for expression of DNA-binding proteins. Nuclear extracts prepared from unstimulated and mitogen-activated cells were studied for their ability to bind to 32P-labelled oligonucleotides containing the AP-1, NF AT, NF-B and CD28RC sites of the IL-2 promoter. Using gel mobility-shift assay, detection of protein binding to the AP-1 site was reduced in SLE compared with controls. NF-AT binding activity was enhanced in all groups of patients, and was associated with measures of disease activity in RA. In addition, SSc patients showed increased NF-kappa B binding activity. Altered patterns of DNA-binding proteins suggest disturbed intracellular signalling which may contribute to abnormal lymphokine production in rheumatic diseases. PMID- 7882555 TI - Synovial cells are potent antigen-presenting cells for superantigen, staphylococcal enterotoxin B (SEB). AB - There is ample evidence suggesting that superantigens may act as a triggering factor in the pathogenesis of rheumatoid arthritis (RA). We investigated whether superantigen could activate T cells in the presence of synovial cells. T cells were cultured with SEB in the presence of interferon-gamma (IFN-gamma)-treated synovial cells. T cell proliferation and activation were assessed by 3H-thymidine incorporation and IL-2 production. The expression of HLA class II antigens and adhesion molecules on synovial cells was detected by flow cytometer. In the presence of IFN-gamma-treated synovial cells, T cells proliferated vigorously and produced IL-2 in response to SEB. A low SEB-induced T cell response was noticed in the presence of untreated synovial cells. Allogeneic as well as autologous IFN gamma-treated synovial cells markedly enhanced SEB-induced T cell proliferation. IFN-gamma-treated synovial cells had increased expression of HLA class II antigens and intercellular adhesion molecule-1 (ICAM-1) adhesion molecules. MoAbs towards these antigens markedly inhibited the SEB-induced T cell response. These results indicate that activated synovial cells are potent antigen-presenting cells for SEB to T cells, and that superantigens may play a critical role in the pathogenesis of RA through activated synovial cells. PMID- 7882556 TI - Effect of Mycoplasma arthritidis superantigen on enzymatically induced arthritis in mice. AB - The objective of this study was to examine the effect of the stimulation of the immune system with Mycoplasma arthritidis superantigen (MAS) on joint inflammation and cartilage destruction. MAS was administered either alone or combined with a model of degenerative arthritis induced by intraarticular injection of collagenase enzyme. Intraperitoneal injection of MAS resulted in activation of peripheral lymphocytes in BALB/c mice, as shown by a proliferative response of splenocytes isolated from MAS-treated animals to IL-2-containing supernatant. Intraperitoneal or intra-articular administration of MAS alone at concentrations maximally activating lymphocytes had no detectable effect on joints. Intra-articular injection of collagenase resulted in some infiltration of inflammatory cells into the joints, hyperplasia and hypertrophy of synovial lining, pannus formation and surface loss of proteoglycans 7 days following the injection. At 21 days, the animals showed almost total loss of cartilage and minimal or no inflammation. Animals receiving MAS in addition to collagenase treatment showed similar changes in the joints. These data have demonstrated that activation of the immune system with MAS in vivo does not increase joint inflammation or cartilage degradation in enzymatically induced arthritis. PMID- 7882557 TI - Avridine-induced arthritis in rats; a T cell-dependent chronic disease influenced both by MHC genes and by non-MHC genes. AB - Avridine is a potent synthetic adjuvant that can induce arthritis is most rat strains. The clinical appearance and histopathology of avridine-induced arthritis show great similarity to other arthritis models such as collagen-induced arthritis. In LEW and DA rats the avridine-induced arthritis is severe and long lasting. To investigate a possible genetic influence on the disease we compared LEW, DA and E3 rats, which are of different genetic origins, for their ability to develop arthritis after injection of a low dose of avridine (1.5 mg/rat). The E3 rat was shown to be resistant, whereas all of the DA rats developed arthritis. Recombinant inbred strains derived from DA and E3 parentals varied in susceptibility to avridine. Only strains sharing RT1av1 with DA developed arthritis, indicating a role for the MHC genes. The MHC association was further analysed in a series of Lewis congenic strains using the 1.5 mg avridine dose. All strains developed arthritis. LEW.1C and LEW.1W developed only acute arthritis, whereas LEW.1A, LEW, LEW.1D, LEW.1N and LEW.1F developed chronic arthritis. In particular, the LEW.1F rats developed a chronic severe arthritis of high incidence. The chronic arthritis showed an active, erosive joint inflammation several months after induction. Nude rats are resistant to avridine induced arthritis, indicating a T cell dependence of the disease which supports the importance of MHC. However, non-MHC genes are also crucial to arthritis development. Recombinants between DA and E3, sharing RT1av1 with DA, showed either a lower incidence or a lower severity of disease than the DA rats. The E3 rat and the recombinants with RT1u were completely resistant, whereas LEW.1W, also RT1u, were highly susceptible. PMID- 7882558 TI - IL-1 beta and IL-6 stimulate the production of platelet-activating factor (PAF) by cultured rabbit synovial cells. AB - The aim of this study was to determine whether synovial cells are capable of producing PAF in the presence of cytokines such as IL-1 beta and IL-6 and other stimuli. Synovial cells were obtained from joints of healthy rabbits. PAF production was assayed by measurement of serotonin release in rabbit platelets and the incorporation of 3H-acetate into PAF. Synovial cells produced PAF after 5 min of incubation with ionophore A23187, reaching the maximal amount at 15 min (4.3 +/- 0.7 x 10(-3) pmol of PAF/mg protein, P < 0.005, n = 4), and declining afterwards. The treatment of synoviocytes with IL-1 beta and IL-6 induced synthesis of PAF after 5 min of stimulation, reaching the greatest production at 15 min with IL-6 and 30 min with IL-1 beta (3.6 +/- 1.1 x 10(-3) and 3.3 +/- 1.2 pmol of PAF/mg protein, respectively, P < 0.05, n = 4). The incubation of the cells with PMSF, an inhibitor of acetylhydrolase, before the addition of the stimuli, increased the incorporation rate of 3H-acetate, suggesting a rapid degradation of PAF by synoviocytes. These results demonstrate that synovial cells can produce PAF after stimulation with agonists, such as ionophore, and cytokines. Thus, PAF, acting alone or with other mediators, could amplify the inflammatory joint reaction. PMID- 7882559 TI - Changes in urinary cytokines and soluble intercellular adhesion molecule-1 (ICAM 1) in bladder cancer patients after bacillus Calmette-Guerin (BCG) immunotherapy. AB - Intravesical immunotherapy for carcinoma in situ of the bladder is arguably the most effective form of tumour immunotherapy described to date. Following repeated instillations of BCG organisms into the bladder, large quantities of cytokines are detected in patients' urine. This study concerns the production of IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and soluble ICAM-1 (sICAM-1) throughout the six weekly instillations which comprise a therapeutic course. Sequential instillations of BCG induced secretion of IL-1 beta, IL-2, IL-6, IL-8, IL-10, TNF alpha, IFN-gamma and sICAM-1 into urine. The responses were heterogeneous between patients and cytokines, but some general trends were evident. Although cytokine levels were initially low, their concentration increased with repeated instillation of BCG. Certain cytokines (e.g. IL-6, IL-8 and IL-10) could be detected after the first instillation, whilst others (e.g. IL-2 and IFN-gamma) were not detected until after the third or fourth instillation. Interestingly, IL 4 was not detected, perhaps suggesting a differential effect on Th2-like responses. Some patients produced particularly elevated or non-detectable levels of cytokines, and a positive correlation was found between the production of various cytokines. The production of a particular cytokine did not correspond with lack of production of another species. Whether monitoring the production of cytokines following therapy may be of prognostic value will be determined in a larger series of patients. However, as these potent immunomodulators are thought to be important for the 75% complete clinical response observed with BCG therapy, there remains the possibility that detection of the products of an activated immune system may correlate with eventual clinical outcome. This study is a necessary forerunner to full prognostic evaluation of such immunological data. PMID- 7882560 TI - Tumour cell binding by a human monoclonal IgM antibody from the spleen of a non tumour-associated patient is due to somatic mutations in the VH gene. AB - Recently we described the occurrence of B cells producing polyspecific natural IgM with anti-tumour specificity in the spleen of non-tumour-bearing individuals as well as in fetal organisms. Immunoprecipitation and 2-D electrophoresis showed the binding of such antibodies to a 55-kD (pI 6.0) membrane surface glycoprotein. In vitro cultivation of human cancer cell lines in the presence of the purified IgM antibodies resulted in growth inhibition and complement-mediated cell lysis. Furthermore, the antibodies were shown to be able to induce MHC class I molecule expression on tumour cells. Because of this, a role for naturally occurring antibodies with anti-tumour specificity in preventing neoplasias had been suggested. We have constructed and expressed in Escherichia coli single-chain fragments (scFv: VH-linker-VL) derived from a polyspecific human monoclonal IgM autoantibody produced by a human x mouse heterohybridoma which was obtained from the spleen of an autoimmune patient. The mutated complementarity determining region (CDR) gene segments were replaced by the equivalent germ-line sequences and the CDR3 region was swapped for that from another polyspecific human natural antibody with no binding to tumours. Using these four scFv constructs for binding analyses and in vitro cultivation experiments we found: (i) scFv containing the mutated VH region of the original antibody were able to bind to tumour cells, to induce MHC class I molecule expression, and to inhibit tumour growth in a way similar to what had been described for the complete antibody; (ii) replacement of the mutated by the germ-line VH gene independently of the CDR3 to which it had been recombined, resulted in failure to bind to tumour cells. Nevertheless, other antigens (ssDNA, tetanus toxin) were still recognized, although with lower affinity. We discuss the significance of the replacement mutations in the VH gene CDRs, selected probably by B cell contact to an (auto)antigen, for generating a tumour binding capacity, not encoded by the germ-line gene. PMID- 7882561 TI - Immunohistological analysis of T cell functional subsets in chronic inflammatory periodontal disease. AB - IL-2, interferon-gamma (IFN-gamma), IL-4 and IL-6 producing T cells in periodontitis and gingivitis-affected human tissues were investigated by immunohistochemistry to clarify the relationship between T cell functional subsets and disease entity. Using alkaline-phosphatase anti-alkaline-phosphatase technique, the relative proportions of each cytokine-producing T cell were calculated in the crevicular 1/3, middle 1/3 and oral 1/3 areas selected in the connective tissue of sections. CD19:CD3 and CD4:CD8 ratios were determined on the serial sections. Compared with gingivitis tissues, the proportion of cytokine producing cells in periodontitis-affected samples was higher overall in the crevicular 1/3 (P < 0.02). The middle 1/3 exhibited a higher percentage of cytokine-producing cells, except for IL-6-producing cells. Frequencies of cytokine-producing cells in the oral 1/3 did not differ. IL-4 was the prominent cytokine in periodontitis-affected tissues, with the highest proportion detected in the crevicular 1/3. The CD19:CD3 ratio was higher in periodontitis tissues irrespective of the location, indicating a B cell dominance in periodontitis lesions. Furthermore, a significant positive correlation between the proportion of IL-4-producing cells and the CD19:CD3 ratio was noted. The CD4:CD8 ratio consistently exceeded 2.0 in both periodontitis and gingivitis. These results suggest that immunoregulation of both periodontitis and gingivitis are T cell dependent, but in periodontitis type 2 helper T cells predominate and thereby control B cell activation. PMID- 7882562 TI - Cytotoxic activity of V beta 8+ T cells in Crohn's disease: the role of bacterial superantigens. AB - In Crohn's disease, disease-related stimuli could alter the T cell receptor (TCR) repertoire. To examine the possibility that changes in function may occur in T cell subsets without obvious changes in expression of TCR, we analysed the TCR repertoire of cytotoxic T lymphocytes in Crohn's disease peripheral blood. Furthermore, we examined the effect of bacterial superantigens, staphylococcal enterotoxin B (SEB) and E (SEE) on the cytotoxic function of T cell subsets bearing different TCR V genes using MoAbs specific for CD3 and TCR V gene products in a redirected cytotoxicity assay. There was no difference between patients and controls in the cytotoxicity measured in concanavalin A (Con A) stimulated peripheral blood mononuclear cells (PBMC) with anti-CD3 or with six of seven anti-TCR V gene MoAbs. However, the cytotoxicity of V beta 8 T cells was decreased in Crohn's disease patients. This was not due to a decrease in total or CD8+ T cells expressing V beta 8. Furthermore, in normal subjects, PBMC stimulation with SEE and SEB selectively expanded and increased the cytotoxicity of V beta 8 and V beta 12 T cells, respectively. In Crohn's disease, although SEB stimulation increased the number and cytolytic function of the V beta 12 subset, SEE stimulation failed to increase cytolytic activity of V beta 8+ T cells in spite of the expansion of V beta 8+ T cells. These results suggest that the changes in cytotoxic function observed in V beta 8 T cells in Crohn's patients may reflect previous exposure to a V beta 8-selective superantigen. PMID- 7882563 TI - Autoimmunity in ulcerative colitis: tropomyosin is not the major antigenic determinant of the Das monoclonal antibody, 7E12H12. AB - Ulcerative colitis (UC) has a proposed autoimmune pathogenesis. A 40-kD antigen (P40) has been isolated from UC colon, bound to immunoglobulin. Tropomyosin has been reported as the target antigen of a MoAb (7E12H12) raised against P40. We set out to investigate whether tropomyosin is the major antigenic determinant for 7E12H12. Formalin-fixed, paraffin-processed and cryostat sections of fresh frozen colon from patients with UC, Crohn's disease and normals, were immunostained with 7E12H12 and commercial anti-tropomyosin antibodies. In addition, the immunoreactivity of 7E12H12 with cytoskeletal components was examined on human endothelial cells (HUVEC) using anti-tropomyosin as a positive control. Con-focal microscopy was used to determine the subcellular localization of signal. An extract of total colonic protein from UC colon was prepared. Using a combination of Western and immunoblotting (dot-blots), the immunoreactivities of both tropomyosin (porcine and chicken) and colon protein extract with either 7E12H12 or commercial anti-tropomyosin were examined. Immunocytochemically, 7E12H12 localized to the apical and basolateral regions of plasma membrane, and to the supranuclear cytoplasm in colonic epithelium. Using anti-tropomyosin antibody it was not possible to identify the cytoskeleton in colonic epithelium. Cytoskeletal components were identifiable in HUVEC cultures with anti-tropomyosin antibody but not with 7E12H12. P40 antigen was identified in the colon protein extract by immunoblotting with 7E12H12. There was clear immunoreactivity between anti tropomyosin antibody and both chicken and porcine tropomyosin, and the colon protein extract. 7E12H12 did not bind to either chicken or porcine tropomyosin in appropriately controlled systems. We conclude that the pattern of immunostaining with 7E12H12 is not cytoskeletal, and there is no reactivity in immunoblots, between tropomyosin and 7E12H12. Tropomyosin is not the major target antigen of this antibody in ulcerative colitis. PMID- 7882564 TI - Oligoclonal activation of CD4+ T lymphocytes in posterior uveitis. AB - Several lines of evidence support an important role for activated T lymphocytes in the perpetuation of autoimmune intraocular inflammatory disease (posterior uveitis). In this study peripheral blood lymphocytes (PBL) were examined by three colour flow cytometry to assess the distribution of IL-2 receptors (IL-2R) among CD4+ and CD8+ T cell subsets in patients with active posterior uveitis and control subjects. Patients with uveitis (n = 70) showed a significant increase in PBL expressing the alpha-chain (Tac) of the IL-2R compared with controls (n = 28) (34.2% versus 29.6%) (P < 0.05). This increased Tac expression was present on both the CD4+ subset (25.7% versus 20.9%) (P < 0.05) and the CD8+ subset (2.5% versus 1.8%) (P < 0.05) of lymphocytes. We also examined whether the activated CD4+ PBL from uveitis patients (n = 30) showed a dominant pattern of T cell receptor (TCR) gene rearrangement, suggestive of an oligoclonal response to a small number of antigenic peptides. A significant increase in the usage of the V alpha 2.3 TCR family by activated but not by non-activated CD4+ PBL was detected in patients (3.9% versus 3.4%) (P < 0.05) compared with controls. There was evidence of oligoclonal activation of CD4+ PBL in 11/30 patients (36.7%) but in none of the controls (n = 10). However, different V alpha or V beta TCR families were selectively activated among and even within individual patients. The heterogeneity in TCR expression among patients with active intraocular inflammatory disease is discussed. PMID- 7882565 TI - Antibodies to the Cryptococcus neoformans capsular glucuronoxylomannan are ubiquitous in serum from HIV+ and HIV- individuals. AB - Murine MoAbs to the Cryptococcus neoformans capsular glucuronoxylomannan (GXM) polysaccharide are protective in mice in vivo and in vitro. The prevalence of protective anti-GXM antibodies in human serum is unknown. To provide further insight into the human antibody response to C. neoformans we determined the prevalence, isotype, and IgG subclass utilization of human anti-GXM antibodies in HIV+ and HIV- sera by a sensitive antigen capture FLISA assay. One hundred and twenty-three sera from the Bronx Municipal Hospital Centre serum bank were studied retrospectively. Seventy were from HIV+ individuals, 10 with a history of cryptococcal meningitis (CM), and 53 were from HIV- individuals. Serum GXM determinations were also performed on 61 HIV+ sera. Our results demonstrated that anti-GXM IgG, IgA, and IgM are ubiquitous in both HIV+ (including those with CM), and HIV- sera. Anti-GXM IgA titres and total serum IgA concentration were elevated in HIV+ sera. Anti-GXM IgG antibodies were almost exclusively isotype restricted to the IgG2 subclass. Our data also demonstrated elevations of anti bovine serum albumin (BSA) titres in HIV+ sera. Taken together, our findings confirm hypergammaglobulinaemia and expansion of anti-protein (BSA) antibodies in HIV+ individuals and isotype restriction of human anti-carbohydrate (GXM) antibodies to the IgG2 subclass. Our report of ubiquitous anti-GXM antibodies of the IgG and IgA isotypes suggests that anti-GXM antibodies exist before HIV infection. PMID- 7882566 TI - In vitro production of cytokines by peripheral blood mononuclear cells from hydatid patients. AB - The role of cytokines in human hydatidosis (Echinococcus granulosus infection) was evaluated in immunoassays determining production of IL-4, IL-10 and interferon-gamma (IFN-gamma) in peripheral blood mononuclear cell (PBMC) cultures from 30 hydatid patients and 14 uninfected controls. In cell cultures from hydatid patients parasite and non-parasite antigen stimulation significantly increased IL-4 production (P < or 0.005). Spontaneous and mitogen-driven IL-4 production was similar in patients and controls. IL-10 and IFN-gamma production did not differ statistically in the two groups, even though some hydatid patients produced these cytokines in large amounts. Notably, antigen-driven IFN-gamma concentrations were invariably higher in patients than in uninfected controls. Data analysis showed a relationship between IgE and IgG4 responses and parasite driven cytokine production. High IgE and IgG4 responders produced high IL-4 and IL-10 concentrations. High IgE responders showed decreased IFN-gamma production, but high IgG4 responders had IFN-gamma levels slightly higher than those of low responders. Cytokine response patterns did not relate to the clinical stage of disease. The significantly increased IL-4 and the high IL-10 concentrations found in PBMC from many hydatid patients in this study are consistent with Th2 cell activation in human hydatidosis. The presence of antigen-driven IFN-gamma production in patients with E. granulosus infection implies concurrent intervention of the Th1 or Th0 cell subset. PMID- 7882567 TI - Blood-stage malaria infection in diabetic mice. AB - Infection of mice with blood-stage Plasmodium yoelii and P. chabaudi malaria induced hypoglycaemia in normal mice and normalized the hyperglycaemia of mice made moderately diabetic with streptozotocin (STZ). Injection of parasite supernatants induced hypoglycaemia accompanied by hyperinsulinaemia in normal mice, and in STZ-diabetic mice induced a profound drop in blood glucose and restored insulin secretion; however, severely diabetic mice (two injections of STZ) remained hyperglycaemic with no change in insulin levels. We conclude that malaria infection and parasite-derived molecules lower blood glucose concentration, but only in the presence of some residual pancreatic function. Diabetic mice were less anaemic, exerted a significant control of parasitaemia, and showed enhanced phagocytic activity compared with normal mice. PMID- 7882568 TI - Antigen-presenting cells in human cutaneous leishmaniasis due to Leishmania major. AB - In this study biopsies from skin lesions and draining lymph nodes of patients suffering from cutaneous leishmaniasis caused by Leishmania major were examined by immunohistochemistry, and by light and electron microscopy to identify the types of antigen-presenting cells (APC) and their location. APC, identified morphologically and by their expression of specific cell markers, included Langerhans cells, macrophages, follicular dendritic cells, and interdigitating reticulum cells of the paracortex of lymph nodes. These cells expressed MHC class II antigens and contained Leishmania antigen. Since some keratinocytes and endothelial cells also showed these characteristics, they may also act as APC. By examining tissue samples from skin lesions and draining lymph nodes it was possible to follow the probable route of trafficking of various inflammatory cells between the skin lesion and lymph nodes. Leishmania antigen containing Langerhans cells were found in the epidermis, dermis and the regional lymph nodes. We believe these cells translocate from the epidermis to the dermis, where they take up antigen and migrate to the paracortex of the regional lymph nodes. There they are intimately associated with cells of the paracortex, and could be involved in the generation of Leishmania-specific T memory cells. LFA-1-positive T cells of the CD45RO phenotype were found in the skin lesion. Venular endothelium in the skin lesions expressed intercellular adhesion molecule-1 (ICAM 1), which is the ligand for LFA-1. The migration of lymphocytes from the vascular lumen to the site of inflammation is possibly a result of the interaction of these two adhesion molecules. PMID- 7882569 TI - Attenuation of immune complex nephritis in NZB/WF1 mice by a prostacyclin analogue. AB - Although prostaglandins have been shown to inhibit the evolution of the nephritis in NZB/W mice, the mechanisms of this effect are unknown. To characterize such inhibition, we injected the prostacyclin (PGI2) analogue, beraprost, into NZB/W mice, using 0.5 mg, 1.0 mg or 5.0 mg beraprost/kg body weight of test animals three times in 1 week when the mice were 2 months old. Evaluation included measurement of urine albumin excretion, serological parameters and splenic T cell subset, as well as examination of renal histology by light and fluorescence microscopy. Mice given beraprost showed a marked decrease in urine albumin excretion and in glomerular hypercellularity compared with untreated controls. Maximal beneficial effects occurred when the dose was 5.0 mg/kg of beraprost. These effects correlated with a reduction of immune complex deposition in glomeruli. In addition, beraprost reduced serum levels of immunoglobulins and anti-double-stranded DNA antibodies, and decreased the number of helper (L3T4+) T cells in splenocytes. These results indicate that beraprost attenuates the nephritis of NZB/W mice, and that the source of this effect is the reduced production of autoantibodies and deposition of immune complexes in glomeruli. PMID- 7882570 TI - Anti-inflammatory activity of salmeterol: down-regulation of cytokine production. AB - Elevation of intracellular cAMP levels has been shown previously to inhibit cytokine secretion by various cell types in vitro. Since salmeterol is a beta 2 agonist which activates adenylate cyclase, its ability to inhibit cytokine production was evaluated. Though salmeterol, and the related drug albuterol, did not inhibit IL-1 beta production in vitro, both drugs did inhibit tumour necrosis factor-alpha (TNF-alpha) secretion by lipopolysaccharide (LPS)-activated THP-1 cells with similar IC50s of approximately 0.1 microM. This inhibition was effectively reversed by the beta 2-antagonist oxprenolol, indicating that the inhibition was mediated through the beta 2-adrenergic receptor. A strikingly different reactivity profile was seen with T cells. Salmeterol was able to inhibit the activation of both mouse and human T cells, as measured by proliferation and IL-2 secretion in response to anti-CD3 antibody, whereas albuterol was completely inactive in these assays. This T cell inhibition by salmeterol was about 10-fold less potent than that for TNF-alpha production, and was not reversed by a beta 2-antagonist, indicating that a different mechanism was involved in the effect of salmeterol on T cells. Paralleling the TNF-alpha inhibitory activity in vitro, oral dosing of salmeterol and albuterol inhibited LPS-induced increase in murine serum TNF level in vivo, with ED50s of approximately 0.1 mg/kg. This inhibition could be abrogated by dosing orally with the beta-blocker propranolol. The long-acting pharmacological profile of salmeterol was apparent in that it maintained its efficacy for 3 h, while albuterol had a much shorter duration of action. Salmeterol also had some protective effects in the galactosamine/LPS model of endotoxic shock, which is dependent upon TNF-alpha production. Though salmeterol inhibited serum TNF-alpha levels by up to 94% in this assay, it protected less than 50% of the animals from the lethal effects of the LPS/galactosamine mixture. This observation suggests that functional levels of TNF-alpha localized in tissues may not be accurately reflected by serum levels. PMID- 7882571 TI - Co-stimulation of T cells via CD28 inhibits human IgE production; reversal by pertussis toxin. AB - In lymphocyte cultures, IgE production was achieved by stimulating T cells with anti-CD2 and IL-2. Here we show that anti-CD28, in the presence or absence of IL 2, reduces this IgE production approximately 10-fold. This inhibition of IgE production was almost completely reversed by Pertussis toxin (PT). PT had no effect on IgE production when the cells were stimulated in the absence of anti CD28. No major effects of PT were found on IgM production. PT had no effect on purified B cells, stimulated with IL-4 and anti-CD40. In the presence of saturating amounts of rIL-4 similar results were obtained, albeit the absolute amounts of IgE produced were higher in all situations. Furthermore, PT-induced IgE production was still dependent on IL-4, as was evident from experiments in which anti-IL-4 was added to the culture. The IgE enhancing effect was dependent on the adenosine diphosphate (ADP)-ribosyltransferase activity of PT, because a mutant molecule lacking this activity was not able to restore anti-CD28-induced inhibition of IgE synthesis. Thus, we show that co-stimulation with anti-CD28 causes an inhibition of T cell-dependent IgE production by B cells, which inhibition can be specifically overcome by PT. An analysis of the molecular pathways underlying this phenomenon may contribute to our understanding of the regulation of IgE synthesis in (patho)physiological conditions. PMID- 7882572 TI - Activated CD4+ T cells preferentially take up lipid microspheres, but resting cells do not. AB - Lipid microspheres (LM) used as drug carriers increase the effectiveness and reduce the toxicity of incorporated drugs. The present study is designed to determine whether or not activated T lymphocytes, which were the cells chosen first from the 'inflammatory cells', can take up LM in vitro. LM were labelled with a fluorescent probe, DiI (DiI-LM), to examine the kinetics. Flow cytometric analysis demonstrated that in freshly isolated peripheral blood mononuclear cells (PBMC), monocytes principally took up DiI-LM, while lymphocytes and granulocytes did not. When PBMC were stimulated with immobilized anti-CD3 MoAb and IL-2, cells expressing CD3, CD4, CD8 and CD16 incorporated DiI-LM. Purified CD4+ T cells, obtained by positive panning selection, were stimulated with this system. They were CD25, CD71, LFA-1-positive, and also showed an ability to take up DiI-LM, which resting cells did not. The findings were confirmed by flow cytometry and quantitative analysis of DiI. Confocal micrographs showed fluorescent granules from the probe in the cytoplasm of stimulated CD4+ T cells after incubation with DiI-LM. These results suggest that immunomodulatory agents incorporated into LM might selectively regulate the function of CD4+ or CD8+ T cells when these are activated. PMID- 7882573 TI - Screening for anti-neutrophil cytoplasmic antibodies (ANCA): is indirect immunofluorescence the method of choice? AB - Detection of ANCA has become an important tool for the diagnosis and monitoring of disease activity in Wegener's granulomatosis (WG). Unfortunately, a group of sera positive by the standard method for ANCA detection, indirect immunofluorescence (IIF), are negative when more specific tests with purified proteins are used. In order to examine this discrepancy we examined groups of sera selected for being (i) C-ANCA-positive by IIF; (ii) positive in proteinase 3 (PR3)-ANCA ELISA; and (iii) from 24 patients with WG. The following assays were used: IIF, PR3-ANCA ELISA and capture PR3-ANCA ELISA using MoAbs against PR3. Furthermore, since granule enzymes are released during coagulation, we also measured ANCA in complex with PR3. To test if granule enzyme release had any influence on ANCA detection, both serum and EDTA-plasma were collected from a patient with active WG. No difference, however, was found. In the IIF-positive group (n = 60) 68% of the sera were positive in PR3-ANCA ELISA, 86% in capture PR3-ANCA ELISA and 80% were positive for the PR3/IgG-ANCA complex. In the PR3 ANCA ELISA group (n = 105) 88% of the sera were positive by IIF, 98% in capture PR3-ANCA ELISA and 53% in the PR3/IgG-ANCA assay. To evaluate the tests clinically sera from 24 patients with WG were examined. In the remission group (n = 10) two patients were positive by IIF, four in the PR3-ANCA ELISA, and five in the capture PR3-ANCA ELISA. Fourteen had active disease, and in this group 11/14 were positive by IIF, 10/14 in PR3-ANCA ELISA and 12/14 by capture-ELISA. The correlation between IIF and capture PR3-ANCA ELISA titre (r = 0.72, P = 0.0095) was better than between PR3-ANCA ELISA and IIF (r = 0.56, P = 0.043). It is concluded that the capture PR3-ANCA ELISA is more sensitive than PR3-ANCA ELISA, and that the capture ELISA can be used for screening of PR3-ANCA. PMID- 7882574 TI - Ion channel modulators as potential positive inotropic compound for treatment of heart failure. AB - 1. Current positive inotropy therapy of heart failure is associated with major problems: digoxin and the phosphodiesterase inhibitors can cause life-threatening toxicity while beta-adrenoceptor agonists become less effective inotropic compounds as heart failure progresses. A new approach to positive inotropy is ion channel modulation. 2. An increased influx of Na+ during the cardiac action potential, as measured with DPI 201-106 and BDF 9148 which increase the probability of the open state of the Na+ channel, will increase force of contraction. 3. Activation of L-type Ca2+ channels with Bay K 8644 will increase influx of Ca2+ and increase the force of contraction. However the Ca2+ channel activators developed to date have little potential for the treatment of heart failure as they are vasoconstrictors. 4. Blocking cardiac K+ channels is a possible mechanism of positive inotropy. Terikalant inhibits the inward rectifying K+ channel, tedisamil inhibits the transient outward K+ channel and dofetilide is one of the newly developed inhibitors of the slow delayed outward rectifying K+ channel. All these drugs prolong the cardiac action potential to increase Ca2+ entry and force of contraction. 5. Thus drugs which increase Na+ influx or block K+ channels represent exciting possibilities for positive inotropy and the potential of these compounds for the treatment of heart failure needs to be fully evaluated. PMID- 7882575 TI - Sodium loads enhance the natriuretic responses to atrial natriuretic peptide and neutral endopeptidase inhibitors in conscious cynomolgus monkeys. AB - 1. The effects of sodium supplements on the renal responses to human atrial natriuretic peptide (hANP 99-126) and to the selective inhibitors of neutral endopeptidase 3.4.24.11 (NEP) SQ 28,603 and candoxatrilat were determined in conscious monkeys. 2. When the monkeys' diet was changed from 0.55% sodium to 1.1% sodium, the natriuretic response to 100 mumol/kg intravenous of SQ 28,603 increased from 665 +/- 64 to 1015 +/- 224 mu Eq/3 h. An acute oral load of 25 mEq sodium significantly increased the natriuresis stimulated by 300 mumol/kg, p.o., of SQ 28,603 from 700 +/- 332 mu Eq/3 h in normal monkey to 2437 +/- 841 mu Eq/3 h. Therefore, the non-human primate model was appropriate for investigating the effects of sodium loads on the urinary ANP and cGMP responses to exogenous ANP in the presence and absence of NEP inhibitors. 3. Graded intravenous infusions of saline increased basal urine volume and excretion of sodium and ANP. Salt supplements enhanced the diuretic, natriuretic and ANP responses to 0.3 nmol/kg intravenous of hANP 99-126 in monkeys treated with vehicle or 10 mumol/kg intravenous of candoxatrilat. The sodium and ANP excretions stimulated by hANP 99 126 were positively correlated with each other and with the calculated intravenous sodium load in the presence or absence of candoxatrilat. 4. SQ 28,603 and candoxatrilat (0.3 to 10 mumol/kg intravenous) each produced significant, dose-related potentiation of the natriuretic, cGMP and ANP responses to 0.3 nmol/kg intravenous of hANP 99-126 in monkeys receiving 5 mL/kg+0.2 mL/min saline. In addition, the highest dose of SQ 28,603 produced significant depressor activity. 5. In conclusion, the increased natriuretic activity of hANP 99-126 in sodium loaded monkeys was mediated, in part, by increased ANP delivery to the guanylate cyclase linked ANP receptors in the distal renal tubules. PMID- 7882576 TI - Enhancement of endothelium-dependent relaxation in the aorta from stroke-prone spontaneously hypertensive rats at developmental stages of hypertension. AB - 1. Endothelium-dependent relaxation (EDR) in aortic rings from young (8 weeks) and adult (16 weeks and 20 weeks) stroke-prone spontaneously hypertensive rats (SHRSP) was investigated in comparison with age-matched Wistar-Kyoto rats (WKY). 2. At 8 weeks, acetylcholine (3 x 10(-9)-10(-5) mol/L) and ionomycin (4 x 10(-8) 10(-6) mol/L)-induced EDR in SHRSP aortae was significantly enhanced compared to that in WKY aortae. Mechanical denudation of the endothelium completely abolished, and pretreatment of aortae with NG-monomethyl L-arginine (1 mmol/L), an inhibitor of nitric oxide formation, greatly reduced the relaxation in both strains. Indomethacin (10(-5) mol/L), a cyclo-oxygenase inhibitor that blocks the production of endothelium-derived contracting factors, did not significantly alter the relaxation by acetylcholine at this age. There was no difference in endothelium-independent relaxation of denuded aortae by sodium nitroprusside (10( 9)-10(-6) mol/L) and 8-bromoguanosine 3', 5'-cyclic monophosphate (10(-6)-10(-3) mol/L). 3. In adult SHRSP with established hypertension, however, the acetylcholine (10(-8)-10(-5) mol/L)-induced relaxation markedly diminished at any of the concentrations tested compared to that observed in 8 weeks old SHRSP and WKY at 8-20 weeks of age. This finding differed from other observations where the relaxation in SHRSP was impaired only at higher concentrations of acetylcholine. Indomethacin pretreatment of aortae from 20 week old SHRSP restored acetylcholine induced EDR to a level comparable with that in age-matched WKY.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882577 TI - The effects of central administration of omega-conotoxin GVIA on cardiovascular parameters and autonomic reflexes in conscious rabbits. AB - 1. The effects of central administration of omega-conotoxin GVIA (omega-CTX), an N-type calcium channel blocker, were examined in conscious rabbits implanted with lateral intracerebroventricular (i.c.v.) cannulae. 2. Experiments were performed over 4 consecutive days. On day 1, the baroreceptor heart rate (induced by glyceryl trinitrate and phenylephrine) and Bezold-Jarisch like (elicited by serotonin) reflexes were measured before (0 h) and 2 h after central administration of omega-CTX (3 or 30 pmol/kg, i.c.v.) or vehicle. On days 2-4, resting parameters and reflexes were again monitored but no further omega-CTX was administered. 3. No change in heart rate (HR) was observed in any rabbit treatment group during the experimental period. In the vehicle (n = 6) and omega CTX 3 pmol/kg (n = 6) groups, small falls in mean arterial pressure (MAP) of 6 +/ 2 and 10 +/- 3 mmHg, respectively, occurred between 0 and 24 h; MAP then remained stable. Baroreceptor-heart rate reflex curve parameters did not change in either of these groups during the 4 day period. 4. Following administration of omega-CTX 30 pmol/kg (n = 7), MAP decreased progressively and by 48 h had fallen by 19 +/- 4 mmHg. Also at 48 h, a 20% decrease in HR range of the baroreceptor heart rate reflex curve was seen without any change in the lower HR plateau from the 0 h control. This indicates that there was an attenuation of the sympathetically mediated upper component of the curve while the vagally mediated component was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882578 TI - Fish protein-rich diet attenuates hypertension induced by dietary NG-nitro-L arginine in normotensive Wistar-Kyoto rats. AB - 1. Dietary 0.023% NG-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthesis, induced hypertension in normotensive Wistar-Kyoto rats (WKY). This hypertension was significantly attenuated in WKY given a fish protein-rich diet. 2. The supplement of 2% L-arginine given in a standard diet or a diet containing 3% taurine for drinking did not significantly affect the development of hypertension induced by L-NNA in WKY. 3. WKY which received the standard diet mixed with 10% urea and 0.023% L-NNA had significantly attenuated hypertension compared with WKY receiving the standard diet mixed with 10% kaolin and 0.023% L NNA. 4. These results suggest that the attenuation of hypertension in L-NNA treated WKY rats given a fish protein rich diet may be partly caused by urea, a metabolic end-product of protein. PMID- 7882579 TI - High fish oil diet increases oxidative stress potential in mammary gland of spontaneously hypertensive rats. AB - 1. The purpose of this study was to determine whether high omega-3 (19% menhaden oil, 1% corn oil) or high omega-6 (20% corn oil) fatty acid diets would decrease expression of hypertension in the female spontaneously hypertensive rat (SHR), promote tumourigenesis in the rat 7,12-dimethylbenz[a]anthracene (DMBA) model of mammary cancer or increase the susceptibility of the mammary gland to lipid peroxidation. A group of rats on a 5% corn oil diet served as the low fat control group. 2. We found that the high omega-3 and high omega-6 fatty acid diets did not significantly decrease mean arterial pressure. Marked differences occurred between the effects of omega-3 and omega-6 high fatty acid diets on baseline oxidation, auto-oxidation and iron-ascorbate catalyzed oxidation. The omega-3 diet showed 675% increase in basal oxidation, a 2624% increase in auto-oxidation and a 4244% increase in iron-ascorbate catalyzed oxidation compared to the omega 6 diet in mammary tissue homogenates. Although all rats were given 5 mg DMBA (i.g.), no mammary tumours were observed in any of the dietary groups. 3. We conclude that: (i) high polyunsaturated fatty acid diets do not decrease blood pressure in the female SHR; (ii) high fish oil diet markedly increases oxidative potential in the mammary gland; and (iii) the female SHR is resistant to DMBA induced tumourigenesis. PMID- 7882580 TI - Kynurenic acid, an endogenous glutamate antagonist, in SHR and WKY rats: possible role in central blood pressure regulation. AB - 1. Kynurenine aminotransferase catalyzes the conversion of kynurenine to kynurenic acid, an endogenous antagonist of excitatory amino acid receptors. The kynurenic acid content and kynurenine aminotransferase activity was measured in micro-dissected regions of spontaneously hypertensive rats (SHR) and their normotensive controls (Wistar-Kyoto rats: WKY). 2. Of the brain regions examined the highest kynurenine aminotransferase activity was found in the medulla followed by the olfactory bulb and the cerebellum, with the spinal cord showing the lowest activity. 3. All samples from SHR showed greatly reduced kynurenine aminotransferase activity compared to WKY. These reductions were most pronounced in the medulla and spinal cord, approximately 45-55%, and lowest in the cerebellum and olfactory bulbs, approximately 25-30%. 4. The kynurenic acid content of the rostral and caudal medulla as well as the spinal cord was also significantly lower in SHR. 5. These results suggest that there may be a deficiency in the kynurenic acid content and kynurenine aminotransferase activity in the SHR. 6. Given the accumulating evidence of the importance of medullary glutamatergic pathways in the control of blood pressure, as well as the higher sensitivity of cardiovascular neurons of SHR to applied glutamate, it seems possible that endogenous kynurenic acid in the brain may play a role in the control of blood pressure and the pathogenesis of experimental hypertension in the SHR. PMID- 7882581 TI - Comparison of salt sensitivity of male and female F2 progeny from crosses between WKY and SHRSP rats. AB - 1. The present study compared the salt sensitivity of male and female F2 progeny obtained from crosses between Wistar-Kyoto/Izumo rats and stroke-prone spontaneously hypertensive rats (SHRSP A3b/Izm) after salt loading for 7 months. 2. Average systolic blood pressure in male F2 progeny was 10 mmHg higher than that of female F2 progeny at 5 months without salt loading. 3. The blood pressure in male F2 progeny was raised significantly 2 months after salt loading, but there was no further significant change in blood pressure even though salt loading was continued for 5 months. 4. In female F2 progeny, however, a significant change in systolic blood pressure was observed 1 month after salt loading and there was a further significant rise in blood pressure over 6 months. 5. Angiotensin I-converting enzyme and RR1023 loci were strongly linked to systolic and diastolic blood pressures in the male but not the female F2 progeny after salt loading for 7 months. 6. We therefore speculate that the hormonal difference between sexes might influence salt sensitivity in the SHRSP. PMID- 7882582 TI - Use of recombinant inbred strains for evaluation of intermediate phenotypes in spontaneous hypertension. AB - 1. The HXB/BXH recombinant inbred (RI) strains, derived from the spontaneously hypertensive rat (SHR) and the normotensive Brown Norway (BN.1x) rat, represent a very useful system for gene mapping and for genetic analysis of certain model diseases, such as spontaneous hypertension. 2. These RI strains were genotyped in multiple genetic polymorphisms and characterized in blood pressure and some intermediate phenotypes. 3. The analysis of RI strains has revealed that (i) a gene in the vicinity of the major histocompatibility complex (RT1) on chromosome 20, a kallikrein-related gene on chromosome 4 and the renin gene on chromosome 13 were significantly associated with blood pressure, and (ii) Na+ leak in red blood cells correlated with blood pressure whereas relative heart and kidney weights as well as platelet aggregation did not. PMID- 7882583 TI - Genes of stress in experimental hypertension. AB - 1. A significant portion of blood pressure variance is modified by the environment. 2. The present report summarizes evidence that: (i) the environmental response is genetically determined; (ii) various stressors can evoke a differential response in hypertensive animals and constitute its intermediate phenotypes; (iii) the response to heat stress can be assigned to a single 'thermosensitivity' locus; (iv) candidate genes of susceptibility to environmental stresses are member(s) of the heat stress gene (HSP) gene families; (v) a restriction fragment length polymorphism of hsp70 and a single base mutation in the 3'-untranslated region of hsp27 are associated with hypertension in recombinant inbred strains. 3. In conclusion, HSP gene variants may be causative in susceptibility to hypertension. PMID- 7882584 TI - Molecular genetics of the SA gene. AB - 1. We have recently identified a candidate gene for rat genetic hypertension, termed SA, by identifying an mRNA species that shows markedly higher expression in the kidneys of spontaneously hypertensive rats (SHR) than in those of Wistar Kyoto rats (WKY). 2. Subsequent genetic co-segregation analyses by ourselves and others indicated that the SA gene locus did indeed influence blood pressure. Moreover, in a preliminary association study, we found an association of a polymorphism of the human SA gene with essential hypertension. 3. Further studies to identify functions of the SA gene products are required before reaching a definite conclusion. PMID- 7882585 TI - Genetics of primary aldosteronism. AB - 1. In 1991 we described a familial variety of primary hyperaldosteronism which was not glucocorticoid-suppressible and was associated with adenoma formation, and called it familial hyperaldosteronism type II (FH-II) in order to distinguish it from the glucocorticoid-suppressible variety described in 1966, familial hyperaldosteronism type I (FH-I). 2. In 1992 the genetic basis of FH-I was clarified by description of a hybrid gene. 3. Primary aldosteronism due to bilateral adrenocortical hyperplasia or to aldosterone-producing tumour can be part of the multiple endocrine neoplasia type I syndrome (MEN I), in which loss of heterozygosity has been described on chromosome 11q13. Loss of heterozygosity at the MEN I locus was found in five of 26 aldosterone-producing tumours from our series (by Japanese collaborators). These included two with adrenal cancer and two with FH-II. 4. We recently described an association of aldosterone responsiveness of aldosterone-producing adenomas with renin gene restriction fragment length polymorphisms, suggesting a possible role for renin genotype and intra-adrenal renin gene expression in the development and biochemical expression of some aldosterone-producing tumours. 5. We found abnormal karyotypes in 13 of 32 benign aldosterone-producing adenomas. PMID- 7882586 TI - Similarity of blood pressure for each genotype of the insertion/deletion polymorphism of the dipeptidyl carboxypeptidase-1 gene in different age groups of patients with severe, familial essential hypertension. AB - 1. The association of alleles of an insertion/deletion polymorphism (I/D) of the dipeptidyl carboxypeptidase-1 gene with hypertension is controversial. If a particular allele makes a major contribution to blood pressure, then hypertensives homozygous for this allele could be expected to have higher high blood pressure than those homozygous for the alternate allele. 2. The present study examined this hypothesis by comparing pretreatment blood pressures of hypertensives who had been genotypes for the I/D polymorphism. Blood pressures for different age groups (< 50, 50-59 and > or = 60 years) were also examined for each genotype. In addition, several other parameters were examined. 3. Systolic blood pressures were found to be 167 +/- 3, 167 +/- 3 and 170 +/- 6 mmHg (mean +/ s.e.) for the genotypes II, ID and DD, respectively. Diastolic blood pressures were 113 +/- 4, 111 +/- 2 and 111 +/- 4, for the respective genotypes. One-way ANOVA showed that the respective blood pressure values did not differ significantly across genotypes. Blood pressures for different age groups of hypertensives were also similar. 4. In addition, body mass index, mean age and sex did not differ between genotypes, either for the group as a whole or for the different age groups. 5. In conclusion, the present study could find no evidence to support a genetic association between the I/D polymorphism of DCP1 and blood pressure in a group with severe, familial hypertension living in Sydney. PMID- 7882587 TI - Frequencies of variants of candidate genes in different age groups of hypertensives. AB - 1. In severe, familial hypertension, we have reported that the proportion of patients homozygous for the deletion allele of an insertion/deletion polymorphism of the angiotensin I-converting enzyme gene is markedly decreased in older age groups, suggesting that this genotype is associated with increased risk of premature death. The aim of the present study was to examine the relationship with age, of variants of other genes that encode proteins having an influence on the cardiovascular system. 2. Genotypes of 13 different variants at 12 relevant genetic loci were determined by either Southern blotting, followed by hybridization probing, or polymerase chain reaction techniques, as appropriate, using genomic DNA extracted from blood leukocytes. Genotype numbers were then assigned to the age categories of < 50, 50-59 and > or = 60 years. 3. Polymorphisms at the atrial natriuretic factor, antithrombin III, renin, angiotensinogen, neuropeptide-Y Y1 receptor, insulin, alpha 2-adrenoceptor, beta 1-adrenoceptor, growth hormone, low density lipoprotein receptor, insulin receptor and renal kallikrein gene loci were found to display similar allele frequencies in each age group of hypertensives, as well as in normotensive controls. 4. In conclusion, we were unable to detect any difference with age for a range of variants of genes whose products have cardiovascular significance, suggesting that, like most polymorphisms, they carry no selective survival advantage or disadvantage in the hypertensive and normotensive population groups studied. PMID- 7882588 TI - Temporal dissociation of the release of the sympathetic co-transmitters ATP and noradrenaline. PMID- 7882589 TI - DNA-mediated immunization and the energetic immune response to hepatitis B surface antigen. AB - A new and unusual approach for evoking an immune response has recently been introduced--that of DNA-based immunization. Purified plasmid DNA, containing protein coding sequences and the necessary regulatory elements to express them, can be introduced into tissues of the organism by means of a parenteral injection or by particle bombardment. The number of cells transfected and the amount of protein produced is sufficient to produce a remarkably strong and broad-based immune response to a wide variety of foreign proteins. The absence of an exogenous infectious agent or immunogen results in the abrupt appearance of a foreign protein within the normal cells of an immunologically mature and healthy animal and provokes an energetic and efficient reaction to this form of antigen presentation. This review summarizes the results obtained with the various experimental models that have been described to date and considers in greater depth the immune response to the surface antigen of the human hepatitis B virus that has been achieved using DNA-based immunization. Several issues are addressed in a prospective manner in order to anticipate some future developments and to point out topics likely to be pertinent to this field. DNA-mediated induction of immune responses may soon be applied as a form of therapeutic treatment. Although this method may constitute a revolution for vaccination, many issues must first be dealt with, especially concerning the safety of using DNA as an immunizing molecule. PMID- 7882590 TI - Antigen-induced programmed T cell death as a new approach to immune therapy. AB - We describe recent advances in understanding a mechanism of peripheral tolerance that operates through antigen-induced programmed cell death of mature T lymphocytes. A three-phase model of this process, termed propriocidal regulation, involves: (i) activation of T cells to express growth lymphokines and their receptors, (ii) lymphokine-stimulated cell-cycle progression, and (iii) T cell receptor reengagement leading to programmed cell death. Based on this model, antigen was used to treat experimental allergic encephalomyelitis and caused profound deletion of autoreactive, encephalitogenic T cells as well as dramatic clinical and pathological improvement of the disease. The potential strengths and weaknesses of this approach to the clinical treatment of T-cell-mediated diseases are discussed. PMID- 7882591 TI - Failure of B cells of chronic lymphocytic leukemia in presenting soluble and alloantigens. AB - B-cell-type chronic lymphocytic leukemia (B-CLL) patients have immunological abnormalities of both B and T lymphocytes. Since T cell defects might depend upon a defective accessory function of neoplastic B lymphocytes, we analyzed the ability of peripheral blood B cells of seven B-CLL patients to stimulate allogenic normal T cells in mixed lymphocyte reaction (MLR) and to present tetanus toxoid (TT) to autologous T cells. In both systems, neoplastic B lymphocytes show a defective antigen-presenting function, which is more evident with disease progression. Such a defect cannot be ascribed to a decreased MHC class II molecule expression nor to an abnormal IL-1 beta production, but it can be partially accounted for by a low B7 expression. Pretreatment of neoplastic B cells with interleukin-4 (IL-4) restores primary MLR, but has little effect on the response to TT. The effect of IL-4 is not mediated by quantitative modifications of class II and B7 molecule expression or of IL-1 beta production. PMID- 7882592 TI - Augmented production of tumor necrosis factor-alpha in obese mice. AB - Non-insulin-dependent diabetes mellitus develops in obesity. The insulin resistance of this disease may be mediated by tumor necrosis factor-alpha (TNF alpha). In particular, the TNF-alpha derived from adipose tissues might be involved in the induction of peripheral insulin resistance in rodent models of obesity. In general, monocytes/macrophages have been considered as the major source of TNF-alpha. This study was designed to examine the potential production of TNF-alpha from monocyte/macrophages in obese mice. In obese (ob/ob) and obese diabetic (db/db) mice, both of which are known to have severe insulin resistance, unstimulated serum bioactivity of TNF-alpha was significantly higher than that in lean control mice. Spontaneous TNF-alpha mRNA expression in splenic macrophages was also enhanced in obese mice, but not in monosodium-L-glutamate (MST)-induced obese mice which have no insulin resistance. In addition, both ob/ob and db/db mice produce more TNF-alpha than lean mice upon in vivo lipopolysaccharide (LPS) stimulation. The LPS-induced increase in serum TNF-alpha activity was not observed in MSG-induced obese mice. Taken together, it is postulated that TNF alpha produced by monocytes/macrophages may also play an important role in the genesis of insulin resistance in obesity. Further study is needed to reveal the mechanism of enhanced TNF-alpha production in obese states and its possible etiologic relevance to obesity. PMID- 7882594 TI - Role of TNF alpha, IL-1, and IL-1ra in the mediation of leukocyte infiltration and increased vascular permeability in rabbits with LPS-induced pleurisy. AB - We examined the generation of tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and IL-1 receptor antagonist (IL-1ra), and their role in the mediation of leukocyte infiltration and increased vascular permeability in rabbits with LPS-induced pleurisy. The leukocyte infiltration was largely mediated by both TNF alpha and IL-1 and could be divided into at least two phases: the early (within 3 hr) phase which was partly inhibited by anti-TNF alpha, but not by IL-1ra, and the late phase (4-12 hr) mediated by both TNF alpha and IL-1, and largely inhibited synergistically with anti-TNF alpha and IL-1ra. Endogenous IL-1ra may be responsible for the downregulation of the late phase of leukocyte infiltration in this type of inflammation. The increased vascular permeability was composed of two phases: immediate (15 min) and delayed (2 hr). The immediate permeability was inhibited by H1-antihistamine but was not affected by anti-TNF alpha, by IL-1ra, or by depletion of neutrophils. The delayed permeability was completely inhibited by either depletion of neutrophils or by anti-TNF alpha and was not affected by IL-1ra or antihistamine. Production of TNF alpha was maintained in the leukopenic rabbits. It would thus appear that the delayed permeability is mediated by a relatively early fraction of leukocyte infiltration initiated by TNF alpha; however, TNF alpha is not the direct mediator of this delayed permeability. PMID- 7882593 TI - Identification of an idiotype associated with antibodies responsible for neuromuscular dysfunction in rats with experimental autoimmune myasthenia gravis. AB - The primary goal of this study was to continue clarifying past observations made by this laboratory indicating that disease severity in experimentally induced myasthenia gravis in Lewis rats is directly determined by the responsiveness and antibody production of a small subset of the total population of acetylcholine receptor (AChR)-responsive B cells. This disease-causing subset of B cells was found to be associated, at least in part, with an idiotypic determinant recognized by a monoclonal anti-Id antibody (11E10) prepared in this laboratory. Since relationships between total AChR antibody titers and neuromuscular disease severity can be inconsistent both in human myasthenia gravis patients and in animal models of myasthenia gravis, the development of a simple serological test for the clonotypic/idiotypic subset(s) of anti-AChR antibody that is most directly responsible for inducing disease symptoms may point to more direct methods of diagnosing and monitoring disease. PMID- 7882595 TI - Summary of the workshop on passive immunotherapy in the prevention and treatment of HIV infection. The Passive Antibody Workshop Participants. PMID- 7882596 TI - Antibodies to the 70-kDa heat-shock protein in patients with thermal burns. AB - Autoantibodies in the sera of patients with thermal burns, which bind to a protein in the intercellular substance of the epidermis, have been previously described. By immunoblot analysis, we have shown that a 68-kDa epidermal protein is the predominant antigen to which these autoantibodies bind. Our study also demonstrates that this 68-kDa epidermal protein is similar to the bovine brain 70 kDa heat-shock protein (hsp 70). In addition, we have detected significantly elevated levels of IgG antibodies to the bovine brain hsp 70 in all of the sera from random burned patients (n = 33), in comparison with the levels in the sera of normal, healthy controls (n = 43, P < 0.0001). The precise role and significance of these autoantibodies and their influence on the immune system in burned patients remain to be determined. PMID- 7882597 TI - Acute renal failure in IgA nephropathy. AB - Twenty-five (3%) of 865 patients with IgA nephropathy presented with acute renal failure (ARF). These patients were matched with 25 patients in the same series who presented with irreversible renal impairment. Patients with acute renal failure had a significantly higher incidence of macroscopic hematuria and red blood cells in tubules. Conversely, a greater percentage of patients with irreversible renal failure had > or = 40% sclerosed glomeruli. The long-term prognosis for patients presenting with ARF appears excellent with only 1 (4%) patient developing chronic renal failure after a mean follow-up of 65 months. Mechanisms of acute renal failure in IgA nephropathy are discussed. PMID- 7882598 TI - Immunohistochemical study of human advanced glycosylation end-products (AGE) in chronic renal failure. AB - In patients with diabetic renal failure plasma advanced glycosylation end products (AGE) levels are reported to be elevated and dialyzer of continuous ambulatory peritoneal dialysis (CAPD) is usually used with a high glucose concentration. Here, an immunohistochemical study on human AGE accumulation in vascular beds and peritonea of patients with chronic renal failure (CRF) or those on CAPD was undertaken. Further, the influence of aging was studied using AGE specific monoclonal antibody. 1. AGE accumulation was observed in radial arterial walls (from vascular intima to smooth muscle layer) of diabetic patients with CRF. Even in some non-diabetic patients with CRF (n = 3/6), especially in those with a long history of CRF and dialysis treatment, similar positive staining was seen in vascular walls. No AGE staining was observed in any renal tissue of age matched control subjects including tissue from patients with acute renal failure. 2. Although AGE accumulation was not seen in the peritonea of CRF patients with no prior CAPD therapy, it was seen in the mesothelial layers and in adjacent coarse connective tissues of peritonea from patients on CAPD (n = 6), even from as early as only 3 months of CAPD therapy. 3. AGE accumulation was observed in the vascular bed of the non-diabetic aged kidney with normal function, but not in that of the young kidney. Thus, AGE accumulation in the vascular bed may depend on the degree and term of renal impairment and on aging in addition to diabetes. AGE accumulation in the peritonea became positive following CAPD treatment, indicating that it might affect the efficiency of CAPD. PMID- 7882599 TI - Uterine artery waveform as a predictor of pregnancy outcome in women with underlying renal disease. AB - To investigate the use of uterine artery flow velocity waveforms in predicting gestational hypertension (GH), preeclampsia (PE) and intrauterine growth retardation (IUGR), Colour Doppler ultrasound of the uterine arteries was performed at 19-24 weeks gestation in 51 women with known renal disease. On four consecutive waveforms, peak systolic (A), end-diastolic (B) and early diastolic (C) velocities were measured. Resistance index (RI) was calculated as (A-B)/A, and the severity of the waveform notch expressed as the AC ratio (A/C). Gestational hypertension was defined as a blood pressure (BP) > or = 140/90 mmHg with an increase of at least 15 mmHg in diastolic BP. PE included women with gestational hypertension and proteinuria > 300 mg/24 h or a doubling of early gestation protein excretion. IUGR was defined as a birthweight less than the 10th percentile for gestation. RI and/or AC ratio in 14 women (27%) exceeded the 90th percentile for gestational age of our low risk control population. Of the women with an abnormal test, 11 (79%) developed complications, 8 (57%) developed GH or PE, 3 (21%) IUGR alone, 2 (14%) GH and IUGR, and in one women intrauterine fetal death of an IUGR infant occurred, and 3 (21%) had an uncomplicated pregnancy. Of the women with a normal test, 34 (92%) had an uncomplicated pregnancy, and only 3 (8%) developed GH or IUGR. In summary, uterine artery waveform indices at 19-24 weeks gestation may be useful for the prediction of pregnancy complications in woman with underlying renal disease. PMID- 7882600 TI - Serum circulating ICAM-1 levels are not useful to indicate active vasculitis or early renal allograft rejection. AB - During inflammation, activated vascular endothelial cells and other cell types express various adhesion molecules which facilitate binding of circulating leukocytes. Serum concentration of circulating adhesion molecule ICAM-1 (c-ICAM 1) is supposed to reflect the degree of this activation. In order to evaluate the usefulness of c-ICAM-1 serum levels for assessment of disease activity in various vasculitic disorders, we examined 23 patients with systemic lupus erythematosus (SLE, n = 9). Wegener's granulomatosis (WG, n = 6), Goodpasture syndrome (GP, n = 6) and microscopic polyarteritis (MP, n = 2). Disease activity was defined by clinical criteria and by conventional laboratory data. Circulating ICAM-1 concentrations were measured during periods of active clinical vasculitis and on clinical remission. In a second part of the study, we examined whether or not c ICAM-1 might be helpful in diagnosing acute allograft rejection early after kidney transplantation. After cadaveric kidney transplantation thirteen patients were included. Serum probes were gathered firstly after transplantation, secondly at time of histologically proven allograft rejection and finally after successful anti-rejection therapy and restored transplant function. c-ICAM-1 levels in healthy volunteers (n = 10) were 270 +/- 47 ng/ml (mean +/- SD). Patients with active vasculitis had mean serum levels of 509 +/- 71 ng/ml (SLE), 594 +/- 118 ng/ml (WG), 472 +/- 126 ng/ml (GP) and 498 ng/ml (MP) (mean +/- SD). In clinical remission, mean serum concentrations were found to be 500 +/- 99 ng/ml (SLE), 597 +/- 84 ng/ml (WG), 782 +/- 163 ng/ml (GP) and 594 ng/ml (MP) (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882601 TI - Effects of age and sex on sodium chloride sensitivity: association with plasma renin activity. AB - The mechanism by which excessive NaCl intake raises blood pressure has not been fully clarified. The present study was undertaken in 87 Japanese inpatients with essential hypertension to investigate the interrelation among effects of age, sex and the renin-angiotensin system on NaCl sensitivity. After ingesting a regular NaCl diet (170 mmol/day) for one week, subjects were placed sequentially on a week of low NaCl diet (50 mmol/day) and a week of high NaCl diet (340 mmol/day). NaCl sensitivity defined as the difference in mean blood pressure between the low and high NaCl diets did not differ between genders. NaCl sensitivity was positively correlated with age and the change in PRA. The fall in PRA after NaCl loading was significantly smaller in women than in men. By multiple regression analysis, age and the change in PRA independently contributed to the change in mean blood pressure. Furthermore, the interaction between sex and the change in PRA was selected as a statistically significant variable. In conclusion, NaCl sensitivity of blood pressure is independently associated with age and the inadequate suppression of the renin-angiotensin system. Because the contribution of the change in PRA to NaCl sensitivity was greater in women than in men, the mechanism of blood pressure elevation after NaCl loading may differ between genders. PMID- 7882602 TI - Renal hemodynamic response to stress is influenced by ACE-inhibitors. AB - Cardiovascular responses to new antihypertensive agents have been studied extensively under resting and stress conditions. However, the effects of antihypertensive agents on renal hemodynamics have only been investigated at rest. To test whether antihypertensive therapy leads to disparate renal hemodynamic effects during exposure to mental stress as opposed to resting conditions, we performed a double-blind, placebo-controlled crossover study. In 17 normotensive healthy men, glomerular filtration rate (GFR; inulin clearance) and renal plasma flow (RPF; para-aminohippuric acid clearance) were measured at rest and after a standardized mental stress test, with or without one week's treatment with a new, long-acting ACE-inhibitor cilazapril 2.5 mg/day. ACE inhibition did not change resting blood pressure, RPF, GFR, or derived parameters, such as filtration fraction, renal vascular resistance and renal fraction of cardiac output. Mental stress caused an acute increase in GFR (p < 0.001) and filtration fraction with both treatments (0.001). However, the increase in GFR and filtration with mental stress was greater (p < 0.05) with cilazapril treatment than with placebo. Thus, renal hemodynamic responses to mental stress were influenced by ACE inhibitors. We conclude that the impact of antihypertensive agents on renal hemodynamics during stress cannot a priori be delineated from measurements at rest. PMID- 7882603 TI - Teicoplanin pharmacokinetics and dosage recommendations in chronic hemodialysis patients and in patients undergoing continuous veno-venous hemodialysis. AB - Multiple-dose pharmacokinetics of teicoplanin, a glycopeptide antibiotic against gram-positive infections, were studied in 9 chronic hemodialysis (HD) patients and in 7 patients with an acute renal failure (ARF) treated by continuous veno venous hemodialysis (CVVHD). After a loading dose of 800 mg i.v. the 400 mg maintenance doses were administered according to a target trough concentration of 5-15 mg/l. Using the Bayesian estimation method implemented in the computer program Abbottbase Pharmacokinetic System (PKS), we defined an open three compartment kinetic model for teicoplanin and calculated the individual pharmacokinetics. The mean terminal elimination half-life was 176 +/- 41.3 h in the HD group and 99 +/- 22.3 h in the CVVHD group (p < 0.005). The total body clearance (CL) was 4 +/- 1.2 ml/min and 9.2 +/- 1.7 ml/min in the HD and CVVHD patients respectively (p < 0.001). The mean reduction of the serum levels during a HD session was 9.1% in the patients dialysed with a F8 filter and 20.2% with a high-flux F60 filter (p < 0.001). The resulting extraction rate was 10 +/- 3.6% (F8) which is similar to the unbound fraction. The elimination of teicoplanin during CVVHD therapy strongly depended on the ultrafiltration rate (UFR) (r = 0.923, p < 0.05). An UFR of 15.6 l/24 h resulted in a removal of 32%/24 h of a 400 mg dose and an UFR of 6.2 l/24 h in 9.5%/24 h respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882604 TI - Effects of erythropoietin on glucose tolerance in hemodialysis patients. AB - Erythropoietin (EPO) therapy is widely used to correct the anemia of end-stage renal disease. It has been reported that this treatment affects various hormonal systems. The aim of the present study was to evaluate the effects of EPO therapy on glucose tolerance. Anemia was corrected with EPO in 10 patients on chronic hemodialysis therapy. Oral glucose tolerance tests (OGTT) were performed before and after correction of anemia. The following measurements were made: the areas under the glucose curves (AUCglue), the areas over basal glucose values (OABVglue), the areas under the insulin curves (AUCins) and the areas over basal insulin values (AOBVins). Hemoglobin concentration increased from 70 +/- 1.4 milligrams to 111 +/- 1 milligram. Fasting plasma glucose, insulin and glucagon levels were were not affected by correction of the anemia. Following administration of EPO, AOBVglue increased by 19%, from 2101 +/- 243 to 2508 +/- 230 mmol.min/l (p < 0.02), while AOBVins remained unchanged. AUCins and AUCglue remained unchanged. These data show that correction of anemia with EPO in hemodialyzed patients causes an increase in the glycemic response to an oral glucose load while not affecting the insulin response. PMID- 7882605 TI - Nephritic urinary sediment in embolic renal infarction. AB - Emboli to the renal arteries occurs most often in patients with underlying cardiac disease. Hematuria is a common feature of renal infarction, but the finding of erythrocyte casts in cases of renal infarction has not been commonly reported. We report a case of renal artery embolization in a patient who had transient nephritic urine sediment, and review the significance of this finding. PMID- 7882606 TI - Pernicious anemia, autoimmune hypothyroidism and rapidly progressive anti-GBM glomerulonephritis. PMID- 7882607 TI - IgA nephropathy associated with pustulosis palmaris et plantaris. PMID- 7882608 TI - Supraventricular tachyarrhythmias: drug therapy versus catheter ablation. AB - Until recently, the only options available for treatment of supraventricular arrhythmias involved the use of drug therapy or cardiac surgery. However, over the past several years with the introduction of radiofrequency energy sources as well as steerable catheters, the clinician has a variety of additional nonpharmacologic options. This article reviews the use of pharmacologic therapy versus catheter ablation for the treatment of reentrant supraventricular arrhythmias, involving the atrioventricular junction and/or accessory atrioventricular connection, as well as arrhythmias emanating from the atria such as atrial fibrillation, atrial flutter, and atrial tachycardia. PMID- 7882609 TI - Should every patient with atrial fibrillation have the rhythm converted to sinus rhythm? AB - Atrial fibrillation is the most common atrial tachyarrhythmia. Consideration for the potential conversion of atrial fibrillation and the subsequent maintenance of sinus rhythm may be related to underlying pathology. Typically, extra cardiac factors such as thyroid hyperactivity help to determine initial therapy. Intrinsic cardiac factors may also influence the clinician's decision regarding potential cardioversion and maintenance of sinus rhythm. Some acute events such as pericarditis and the effects of cardiac trauma may resolve and result in spontaneous restoration of sinus rhythm. Other cardiac events such as acute myocardial infarction with or without atrial ischemia, valvular disease, and others may result in the precipitation of atrial fibrillation. The major reasons to consider cardioversion, either medically or electrically, are ventricular rate control, hemodynamic improvement, sense of well being, and the avoidance of embolism. Certain clinical situations (e.g., Wolff-Parkinson-White syndrome) require urgent restoration of sinus rhythm in light of the potential for extremely rapid ventricular rates. It has been suggested that all antiarrhythmic drug administration should be initiated in the hospital setting, but the brief period of drug administration in an inpatient setting does not protect the patient from potential, late-onset proarrhythmic events. Both antiarrhythmic drug therapy and electric cardioversion are useful for restoration of sinus rhythm in both acute and chronic atrial fibrillation. The most important negative aspect of drug conversion of atrial fibrillation may be the potential development of a proarrhythmic drug effect. Although controversial, conversion (medical or electrical) is probably indicated in every patient with the first episode of persistent atrial fibrillation, even if the patient is asymptomatic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882610 TI - An approach to therapy of supraventricular tachyarrhythmias: an algorithm versus individualized therapy. AB - Approaches to the treatment of supraventricular arrhythmias, including atrial fibrillation, atrial flutter, atrial tachycardia, atrioventricular (AV) reentrant tachycardia, and AV nodal reentrant tachycardia, continue to evolve. Within the past two decades, many new and effective treatments have become available. These include several new antiarrhythmic agents, ablative therapies, pacing and surgical modalities, and cardioversion/defibrillation techniques. This paper provides an algorithm for the treatment of these supraventricular arrhythmias which includes therapy for the acute episode as well as the prevention of subsequent episodes of the tachyarrhythmia. PMID- 7882611 TI - Structural heart disease: its importance in association with antiarrhythmic drug therapy. AB - The presence or absence of structural heart disease is an important factor to consider prior to initiating antiarrhythmic drug therapy with a class I or class III antiarrhythmic agent. An appropriate screen for structural heart disease and other associated proarrhythmic risk factors should include a complete history, physical examination, electrocardiogram (ECG), and echocardiogram in all patients; exercise test and Holter monitoring in many/most selected patients; and a signal-averaged ECG, chest x-ray, and invasive procedures only in selected/occasional patients. Whether and when to obtain the tests that are not indicated for all patients must be determined by each individual physician's practice strategy and philosophy, while keeping in mind the likelihood of finding an abnormality in a particular patient, the arrhythmia being treated, the nature of the drug to be used, and cost-effectiveness issues. Given the low incidence of proarrhythmia under most circumstances, screening for clinically unrecognized structural heart disease may appear difficult to justify in the current era of cost containment. However, due to the potential lethality of proarrhythmia, particularly in patients with structural heart disease, pre-drug assessment is prudent. PMID- 7882612 TI - Inpatient versus outpatient initiation of antiarrhythmic drug therapy for patients with supraventricular tachycardia. AB - In-hospital initiation of antiarrhythmic drug therapy is often recommended to observe the effects of the drug and monitor for possible adverse reactions, especially proarrhythmia. However, the actual risk of proarrhythmia in patients undergoing treatment for supraventricular tachyarrhythmias is not well defined. While patients with ventricular tachycardia or ventricular fibrillation most often have underlying structural heart disease, this is not true for many patients with supraventricular tachycardia. It is therefore necessary to define more precisely which patients with supraventricular tachycardia are at risk for ventricular proarrhythmia and sudden cardiac death. An indepth analysis was conducted of 162 patients from 51 published reports of ventricular proarrhythmic events in patients treated for supraventricular tachycardia. Heart disease of various etiologies was present in 96% of patients. Proarrhythmia occurred most commonly with quinidine (72% of cases), and torsade de pointes was the most frequently proarrhythmic event (54%). More than half of all proarrhythmic events occurred within the first 3 days of initiating therapy or soon after increasing the dose of chronic drug therapy. Information was scant regarding the time to occurrence of ventricular proarrhythmia with flecainide and propafenone. With flecainide, nine cases were reported at varying times after initiation of therapy, from in-hospital to 8 months. Two cases of proarrhythmia with propafenone occurred at Day 10 and at 2 years. Because of the low frequency of proarrhythmia, in-hospital initiation of antiarrhythmic drug therapy may not be cost-effective. It is recommended when the effects of the drugs on the arrhythmia must be monitored, or when initiating treatment or increasing the drug dose in patients with structural hear disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882613 TI - Malignant progression of B16 melanoma cells induced in vitro by growth factors produced by highly malignant cells. AB - Four mouse B16 melanoma subclones (G3.15, G3.5, G3.12 and G3.26) exhibit progressively greater growth capacity in vitro and in vivo. Previously, non metastatic G3.15 cells were sequentially converted, in monolayer cultures, to the moderately-metastatic G3.5 cells, and then to a highly-metastatic G3.5* phenotype. Both conversions were induced by hypoxia followed by confluence, and also occurred in tumors. G3.5* cells were comparable with, yet distinguishable from, G3.12 cells in being growth-autonomous in culture. In this study, the presumption that rapidly-growing G3.26 cells represented the ultimate progression step in this clonal system was examined. Both G3.12 and G3.5* cells converted in vitro to the G3.26 phenotype during growth in serum-free medium conditioned by G3.26 cell growth. By selective filtration of conditioned medium and characterization of the stability of growth- and conversion-promoting activities, three distinct activities were found to promote a two-step G3.12 to G3.26 phenotype conversion: (1) a < 10 kDa filtrate stimulated slight attachment and proliferation of G3.12 cells, effects that were reversible, partly attributable to accumulated lactate, and fully mimicked by medium acidification to pH 6.5; (2) medium acidification, together with a heat- and acid-stable but partially trypsin sensitive > 10 kDa activity, induced G3.12-->G3.5* conversion that resulted in acquisition of growth autonomy; and (3) a heat-, acid- and trypsin-sensitive > 10 kDa activity induced G3.5*-->G3.26 conversion, characterized by anchorage independent growth in soft agar, and potent lung colonization following intravenous injection. Phenotype analysis of G3.12 tumors and lung metastases revealed that G3.5*-like cells were regularly present in tumors and metastases, whereas G3.26-like cells occurred almost exclusively in large lung metastases. While G3.12 cells might convert to G3.5* cells in order to disseminate, G3.26 cells are apparently not involved in metastatic spread but probably account for the rapid growth of established metastases. PMID- 7882614 TI - Effects of suramin on metastatic ability, proliferation, and production of urokinase-type plasminogen activator and plasminogen activator inhibitor type 2 in human renal cell carcinoma cell line SN12C-PM6. AB - Effects of suramin, a polysulfonated naphthylurea compound, on metastatic ability, proliferation, and production of plasminogen activators and plasminogen activator inhibitors were studied using the highly metastatic human renal cell carcinoma cell line, SN12C-PM6. After renal subscapular implantation of tumor cells in nude mice, suramin significantly inhibited metastasis of tumor cells to the lungs and liver. In vitro growth of tumour cells was inhibited by suramin in a dose-dependent manner, at relatively low doses (ID50 = 105 micrograms/ml). Plasminogen activator inhibitor type 2 (PAI-2) production by tumor cells was enhanced by suramin (100 micrograms/ml), whereas urokinase-type plasminogen activator (uPA) production was suppressed. Thus, the increase in PAI-2 and the decrease in uPA production correlated with the inhibitory effects on tumour growth and metastasis by suramin. Therefore suramin may be beneficial for the treatment of patients with an early stage of renal cancer with potential risk of metastasis. PMID- 7882615 TI - Role of phospholipase D in laminin-induced production of gelatinase A (MMP-2) in metastatic cells. AB - Metastatic spread depends critically upon the invasiveness of tumor cells, i.e. their ability to breach basement membranes by elaborating and secreting specific proteolytic enzymes such as gelatinase A (MMP-2). Laminin is a major constituent of the extracellular matrix that can trigger production of MMP-2 in metastatic cells, but not in non-metastatic cells. The present study was designed to examine the role of phospholipase D (PLD) and its product, phosphatidic acid, in the intracellular signal transduction mechanisms that mediate induction of MMP-2 by laminin. Here we show that stimulation of tumor cells with laminin results in a time- and dose-dependent activation of PLD. Laminin-induced production of MMP-2 is attenuated by 1-butanol, a competitive substrate of PLD that reduces PLD catalyzed production of PA. Moreover, phosphatidic acid itself can induce production of MMP-2 in metastatic tumor cells. MMP-2 can also be induced by exposing the cells to exogenous bacterial PLD. Elevated cellular phosphatidic acid induces MMP-2 in metastatic ras-transformed 3T3 fibroblasts but, like laminin, fails to do so in normal cells. These data indicate that laminin-induced activation of PLD and consequent generation of phosphatidic acid are involved in a signal propagation pathway leading to induction of MMP-2 and enhanced invasiveness of metastatic tumor cells. PMID- 7882616 TI - Determinants of differential liver-colonizing potential of variants of the MCA-38 murine colon cancer cell line. AB - We investigated factors that might contribute to the differing liver tumor colonizing potentials of MCA-38 colonic cancer cell line variants injected into the ileocolic veins of C57Bl/6J mice. Non-colonizing (MCA-38 CD) cells were sensitive to lysis by hepatic natural killer (NK) cells in vitro (51Cr-release assay) and cells with high liver-colonizing potential (MCA-38 LD) were resistant. Following abrogation of NK activity by treatment with anti-asialoGM1, liver colonizing ability to LD cells but not CD cells was enhanced. MCA-38 CD cells were, however, capable of initial liver colonization after ileocolic vein injection. Differing patterns of membrane sialylation may have contributed to the contrasting hepatic tumorigenicities of LD and CD cells; beta-galactoside alpha 2,6-sialyltransferase mRNA levels and activity were approximately four-fold higher in LD than CD cells and qualitative and quantitative differences existed between their ganglioside profiles. In the MCA-38 model outlined, tumor cell susceptibility or resistance to NK lysis was a relatively unimportant determinant of liver-colonizing potential. PMID- 7882618 TI - Marked induction of gelatinases, especially type B, in host fibroblasts by human ovarian cancer cells in athymic mice. AB - Two human ovarian adenocarcinoma cell lines, MCAS-3 and OVISE-3 were found to secrete little of any type of gelatinase in tissue culture. However, when these cell lines were implanted subcutaneously into nude mice the cyst fluids from the resultant tumors contained gelatinase A and/or B. The enzyme activities, especially of gelatinase B, were much higher in the malignant MCAS-3 tumors than in those of the less malignant OVISE-3 tumor cells. To elucidate the origin of gelatinase B in cyst fluids of the MCAS-3 tumors, murine skin fibroblasts (MSF) were isolated from a subcutaneous tumor in a nude mouse and tested for their proteinase secretion in culture. MSF cells, which secreted some gelatinase A and gelatinase B, were induced to secrete high levels of both enzymes, especially gelatinase B, by co-cultivation with MCAS-3 cells. In addition, gelatinase A activity was induced by incubation of MSF cells with the conditioned medium of either MCAS-3 or OVISE-3 cells, whereas gelatinase B was induced only with that of MCAS-3. Although cytokines or growth factors such as IL-1 beta, TGF-beta 1, TNF-alpha or EGF stimulated the secretion of gelatinases A and B from MSF cells, their effects on gelatinase B activity were far less than that of the MCAS-3 conditioned medium. These results indicate that the major part of gelatinase B activity in the cyst fluids of the ovarian tumors is secreted by host interstitial cells stimulated by tumor-derived humoral factors. Similar tumor cell-host cell interactions may be important in the production of various proteinases in other tumor types. PMID- 7882620 TI - Instruments and equipment used in operative laparoscopy. AB - Successful operative laparoscopy is dependent on the proper use and knowledge of a variety of appropriate surgical equipment. This chapter describes cameras, light sources, videos, video positioning, operating tables, anaesthesia, insufflators, laparoscopes, trocars, irrigators, forceps, scissors, electrosurgical instruments, lasers, suturing, staples and uterine manipulators. Knowledge of the best choice and proper use of instruments has a more important role in performing operative laparoscopy than laparotomy. PMID- 7882619 TI - Effects of prolonged treatment with decarbazine on tumor metastatic potential in mice bearing Lewis lung carcinoma. AB - The effects of decarbazine on tumour growth and metastatic dissemination upon treatment protracted for 10 tumour transplant generations were examined in mice bearing Lewis lung carcinoma. Primary tumour growth is unaffected by the drug, independently from the duration of the treatment. In contrast, dacarbazine significantly inhibits the formation of lung metastasis. The proportion of mice with metastasis decreases for an increasing number of transplant generations of treatment, and after 10 transplant generations of treatment metastatic capacity is completely lost in immunocompetent mice. The reduction in metastatic potential is relatively stable, being retained for three successive transplant generations without treatment. The metastatic potential of treated tumours in immunosuppressed mice is substantially similar to that in immunocompetent hosts, indicating that chemical xenogenization of tumour cells does not occur as reported for transplantable mouse leukaemias. The results obtained using clonally selected tumour lines with different metastatic potential rule out the selection by dacarbazine of tumour cell sublines with reduced metastatic potential as the mechanism of the drug's action. Upon prolonged treatment, dacarbazine appears to cause a rather stable and dramatic loss in metastatic potential, not accompanied by resistance, which might be attributed to genotypic alteration(s) of tumour cells, and which might participate into the clinical effects of the drug. PMID- 7882621 TI - Endoscopic management of ectopic pregnancy. AB - The rationale for the conservative management of ectopic pregnancy is the preservation of reproductive potential. Removal of trophoblast through a linear incision (salpingotomy) can be easily performed by endoscopy. The injection of vasopressin into the broad ligament is required in less than 10% of cases and its routine use is not recommended because of the risk of severe side-effects. The techniques in cases of isthmic or cornual tubal pregnancy are also described. Other alternatives such as expectant management, methotrexate, RU 486 and prostaglandins have also recently been proposed. Although methotrexate therapy has been demonstrated to be effective in cases of unruptured tubal pregnancy, further studies are needed to determine whether or not this medical therapy is a safer option than laparoscopic surgery and to compare the subsequent intrauterine and recurrent ectopic pregnancy rates. Endoscopic salpingotomy is an efficacious procedure. Indeed, residual trophoblast is found in only 5% of cases after this surgical procedure. In these cases of persistent trophoblast, methotrexate is proposed as the medical approach of choice. Evaluation of the postoperative fertility after linear salpingotomy demonstrates an intrauterine pregnancy rate of 63% and a recurrent ectopic pregnancy rate of 8%. In conclusion, endoscopic management of tubal pregnancy is a safe and efficacious therapy. The contraindications are relative and depend essentially on the surgeon's experience. PMID- 7882617 TI - The role of trophic factors and autocrine/paracrine growth factors in brain metastasis. AB - The brain is a unique microenvironment enclosed by the skull, lacking lymphatic drainage and maintaining a highly regulated vascular transport barrier. To metastasize to the brain malignant tumor cells must attach to microvessel endothelial cells, respond to brain-derived invasion factors, invade the blood brain barrier and respond to survival and growth factors. Trophic factors are important in brain invasion because they can act to stimulate this process. In responsive malignant cells trophic factors such as neurotrophins can promote invasion by enhancing the production of basement membrane-degradative enzymes (such as type IV collagenase/gelatinase and heparanase) capable of locally destroying the basement membrane and the blood-brain barrier. We examined human melanoma cell lines that exhibit varying abilities to form brain metastases. These melanoma lines express low-affinity neurotrophin receptor p75NTR in relation to their brain-metastatic potentials but the variants do not express trkA, the gene encoding a high affinity nerve growth factor (NGF) tyrosine kinase receptor p140trkA. Melanoma cells metastatic to brain also respond to paracrine factors made by brain cells. We have found that a paracrine form of transferrin is important in brain metastasis, and brain-metastatic cells respond to low levels of transferrin and express high levels of transferrin receptors. Brain metastatic tumor cells can also produce autocrine factors and inhibitors that influence their growth, invasion and survival in the brain. We found that brain metastatic melanoma cells synthesize transcripts for the following autocrine growth factors: TGF beta, bFGF, TGF alpha and IL-1 beta. Synthesis of these factors may influence the production of neurotrophins by adjacent brain cells, such as oligodendrocytes and astrocytes. Increased amounts of NGF were found in tumor-adjacent tissues at the invasion front of human melanoma tumors in brain biopsies. Trophic factors, autocrine growth factors, paracrine growth factors and other factors may determine whether metastatic cells can successfully invade, colonize and grow in the central nervous system. PMID- 7882622 TI - Laparoscopic management of adnexal masses. PMID- 7882623 TI - Endoscopy in the management of endometriosis. AB - Endoscopy has replaced laparotomy in nearly all patients requiring surgical treatment of endometriosis. Controlled trials have shown electrosurgery is more effective than expectant treatment in the resolution of infertility due to peritoneal endometriosis and equally effective as laparotomy. Laparoscopy surgery reduces patient morbidity and costs when compared with laparotomy. No significant difference has been demonstrated between laser or electrosurgery in resolving infertility related to peritoneal endometriosis. Peritoneal endometriosis is difficult to diagnose and its extent is obscured by occult endometriosis in microscopic foci. Biopsy is required to establish the diagnosis as all of the described lesions of endometriosis may also be due to other diseases. Excision of the lesions may be by electrosurgery, laser or scissor diathermy. Scissor diathermy has advantages over laser or electrosurgery. Endometriomas may be removed by one- or two-stage excisional surgery. Follow-up laparoscopy is often indicated because of the association with secondary adhesive formation. Pouch of Douglas endometriosis requires special attention to the identification of the extent of disease and the technique of removal. Rectal involvement may require rectal surgery, most of which can be achieved by laparoscopy. Hysterectomy and oophorectomy may be performed laparoscopically and are indicated for recurrent extensive disease not controlled by medical or conservative surgical procedures, for adenomyosis or for extensive pelvic adhesions. PMID- 7882624 TI - Role of laparoscopy in the management of pelvic adhesions and pelvic sepsis. AB - Operative laparoscopy in pelvic sepsis is useful in acute cases: (a) for diagnosis, as there are 20-30% false positive and false negative diagnoses based on clinical and laboratory data alone; and (b) for treatment in severe cases and mainly in tubo-ovarian abscesses, laparoscopy allows aspiration of purulent discharge and, in recent cases, removal of fresh adhesions. In most cases, rapid and complete recovery is associated with treatment with an effective polyvalent antibiotic. Fertility is also preserved in most cases as assessed by a small series of bilateral abscesses with long-term follow-up. In CS associated with infertility, laparoscopic treatment is limited to velamentous adhesions or to dense adhesions of small extent. If performed after the completion of the inflammatory episode, laparoscopic surgery can give results comparable to those of microsurgery. A full bacteriological investigation and appropriate antibiotic treatment are necessary in order to stop or reduce the inflammatory condition which is usually associated with the development of adhesions and is a possible cause of their recurrence. PMID- 7882625 TI - Laparoscopic myomectomy and tubal reconstructive surgery in the infertile patient. AB - This chapter describes the surgical management of uterine fibroids and tubal disease using laparoscopy as a means of access. In both instances the discussion is restricted to attempts to enhance fertility. Myomectomy and tubal reconstructive surgery are totally different procedures and each is discussed separately. PMID- 7882626 TI - Laparoscopic treatment for genuine urinary stress incontinence. AB - Among various operations for stress urinary incontinence, the retropubic colposuspension (Burch procedure) has the best long-term result for treatment of genuine urinary stress incontinence caused by hypermobility of proximal urethra and the urethrovesical junction. With advanced technology in operative laparoscopy. Burch colposuspension can be performed laparoscopically without difficulty and it can achieve the same therapeutic result as the traditional open surgery. Laparoscopy provides better visibility of the operative field, more precise placement of paraurethral sutures and satisfactory haemostasis. Patients who undergo laparoscopic Burch procedure experience less postoperative discomfort, quicker recovery, fewer operative complications, and better cosmetic appearance. PMID- 7882627 TI - Laparoscopic hysterectomy. AB - Laparoscopic hysterectomy is a substitute for abdominal hysterectomy and not for vaginal hysterectomy. Most hysterectomies currently performed with an abdominal approach may be performed with laparoscopic dissection of part or all of the abdominal portion followed by vaginal removal, including fibroids of 1000 g. There are many surgical advantages, particularly magnification of anatomy and pathology, easy access to the vagina and rectum, and the ability to achieve complete haemostasis and clot evacuation during underwater examination. Patient advantages are multiple and are related to avoidance of a pain producing abdominal incision. They include a reduced period of hospitalization and recuperation and an extremely low rate of cuff infection and ileus. It must be emphasized that conversion to laparotomy when the surgeon becomes uncomfortable with the laparoscopic approach should never be considered a complication; it is rather a prudent surgical decision that will profoundly decrease patient risk. The laparoscope can be used in combination with hysterectomy in a variety of ways with significant surgical and patient advantages. With few exceptions, laparoscopic hysterectomy can replace abdominal hysterectomy. Surgical outcome is the same. In experienced hands, the complication rate is low. Patient benefits are related to avoidance of an abdominal incision and include improved cosmetics and more rapid recovery. PMID- 7882628 TI - Endoscopic classic intrafascial supracervical hysterectomy without colpotomy. PMID- 7882629 TI - Operative laparoscopy in gynaecological oncology. AB - Initial reports on the role of laparoscopy in gynaecological malignancies have centred around staging procedures. Laparoscopic lymphadenectomy, both pelvic and para-aortic, appears to be feasible and adequate. It appears that laparoscopy may play an important role in reviving the radical vaginal hysterectomy for patients with early cervical cancer. Similarly, an abdominal incision may be avoided in patients with early endometrial carcinoma by employing laparoscopic staging with vaginal hysterectomy. The role laparoscopy will play in ovarian cancer is still to be defined, and laparoscopic advocates must be cautious in this subset of patients. However, for those gynaecological oncologists employing second-look procedures, it appears that beginning with laparoscopy may make laparotomy unnecessary in the majority of patients. Survival data for patients with gynaecological malignancies managed using laparoscopy in lieu of laparotomy are still lacking. It is imperative that survival is not compromised by employing a new surgical technique. Cost data comparing laparoscopy to laparotomy in our subspeciality is unavailable. This increasingly important aspect of medical care may influence the future of laparoscopy. These and other important issues need to be addressed by future trials before the role of laparoscopy in gynaecological oncology can be determined. PMID- 7882630 TI - Videolaseroscopy and videolaparoscopy. AB - Laparoscopic surgery is not a new idea, but it has only recently found widespread acceptance. The introduction of technological advances such as improved light sources, lasers and video capability has made laparoscopy a surgical technique that offers many advantages to the patient and the surgeon. Because videolaseroscopy must be performed using a completely different set of skills, the only limit to the expansion of this type of surgery is training enough surgeons to meet the growing demands of the public. We believe that videolaseroscopy will become a larger part of the surgical operations performed in the future as technology becomes available to improve upon the instruments and methods. PMID- 7882631 TI - Complications of the laparoscopic approach. AB - Most laparoscopic complications occur as a result of creating and maintaining a pneumoperitoneum and the blind insertion of the first trocar. Thus, it is the complications of the laparoscopic approach rather than the complications of the laparoscopic technique for a specific condition which should be considered. The hazards and the incidences, causes, prevention and management of these complications are discussed using the experience of the author and reported data. PMID- 7882632 TI - Training and regulation for endoscopic surgery. PMID- 7882633 TI - Women in clinical drug trials. An update. PMID- 7882634 TI - Pefloxacin clinical pharmacokinetics. AB - Pefloxacin has a broad spectrum of activity against a great number of Gram negative and Gram-positive bacteria. It is also capable of penetration into cells, yielding high tissue:serum ratios, with implications for the treatment of infections caused by intracellular pathogens. Pefloxacin is well absorbed from the gastrointestinal tract. Its elimination half-life ranges from 6.2 to 12.4 hours. After repeated administration, a major change in pharmacokinetic parameters is observed. Pharmacokinetic parameters are minimally altered or not altered in patients with impaired renal function. Altered plasma pharmacokinetics in patients with liver insufficiency and in elderly patients are observed, so dosage adjustments are necessary. In addition, pefloxacin interacts with a number of other compounds at hepatic (e.g. theophylline and cimetidine) and gastrointestinal (e.g. antacids) sites. With the exception of saliva, cerebrospinal fluid, aqueous humor, vitreous fluid and amniotic fluid, body fluid concentrations reach plasma concentrations. Studies on tissue penetration show that concentrations exceeding plasma concentrations are obtained in most tissues. The highest tissue:plasma concentration ratios are achieved in lung and kidney, whereas concentrations in fat are considerably lower than those in plasma. PMID- 7882635 TI - Pharmacokinetic drug interactions with gastrointestinal motility modifying agents. AB - Drugs may affect gastrointestinal motility and, therefore, absorption of other concomitantly administered drugs. Gastrointestinal prokinetic agents increase the rate of gastric emptying and also upper intestinal motility. These effects would be expected to increase the initial rate of absorption of orally administered drugs, but reduce total bioavailability of the agents. Metoclopramide has been shown to increase the rate of absorption of several classes of drug, reflected by reduced time taken to achieve maximal plasma concentration (tmax) and increased maximal plasma concentration (Cmax). However, the effect of these agents on the area under the plasma concentration-time curve from zero to infinity (AUC0 infinity), when measured, is not consistent. Cisapride and domperidone appear to have similar effects, but there are relatively less data available regarding these products. Opioids may delay gastric emptying considerably, an effect which will often have significant clinical and therapeutic implications. Most of the data confirming this observation concern oral analgesics, but the effect should be considered when prescribing any oral medication. Drugs with anticholinergic or sympathomimetic activity are likely to have a similar effect and this is confirmed, in the main, by the limited data available. Although many effects reported in the literature are of limited clinical importance, they may be significant when prescribing a drug with a narrow therapeutic index, especially if it is absorbed poorly. PMID- 7882638 TI - Screening general obstetric populations for risk assessment. Who will need testing? AB - In spite of increasing emphasis on high-technology aids for antepartum screening, diagnosis, and care, the first steps to secure better outcomes for most pregnancies begin with basic preconception and early prenatal risk assessment. Although many well-studied tools are available for prospective care of the high risk fetus, the impact of many maternal risk factors occurs prior to the time such approaches can be invoked. It is becoming more evident that preventive care may reduce or eliminate the toll exacted by some of the more frequent problems, such as poor nutrition, substance abuse, or failure to comply with effective regimens for treating common medical disorders. Schemes for reducing perinatal mortality place a premium on engaging the patient in her own risk management and early identification of problems. The role of patient education cannot be overemphasized. Making the pregnant woman an active member of her caretaking team is a good investment in time and effort. PMID- 7882639 TI - Is routine ultrasound screening for all patients? AB - The issue of routine ultrasound screening is addressed through an analysis of previous randomized trials in Europe and the United States. Potential benefits of offering ultrasound examination to low risk patients are explored, including detection of anomalies, diagnosis of multiple gestation, and reduction in induced labors for erroneous diagnoses of postdatism. The most recent US routine antenatal diagnostic imaging ultrasound (RADIUS) study is summarized and analyzed. Principles of obstetric ethics as applied to the use of routine ultrasound examination are developed and discussed. The responsibilities of those involved in providing such services are described. It is our opinion that routine ultrasonography has a favorable risk to benefit ratio and suggest that it should be offered. PMID- 7882637 TI - Optimisation of antirheumatic drug treatment in pregnancy. AB - Active rheumatic disease during pregnancy may require drug treatment to ensure the mother's health is maintained and that there is a good outcome for the fetus. However, knowledge on the use of antirheumatic drugs during pregnancy is limited, rendering decision making difficult both for the patient and the physician. The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis has been investigated in depth for aspirin (acetylsalicylic acid) and indomethacin only. Information about the use of ibuprofen, sulindac, ketoprofen and diclofenac during pregnancy is scanty and there is no such information for newer agents such as the fenemates and oxicams. There is no evidence for teratogenicity of any NSAID in humans. However, due to the shared property of inhibition of prostaglandin synthesis, adverse effects such as constriction of the ductus arteriosus in utero, persistent pulmonary hypertension in the neonate and prolongation of pregnancy and labour are possible. When administered to pregnant patients, NSAIDs should be given in the lowest effective dose, and should be withdrawn within the 8 weeks prior to expected delivery. Transplacental passage varies for different corticosteroids. Because of the inability of the fetal liver to convert prednisone to its active metabolite and the ability of the placenta to convert prednisolone to the inactive prednisone, both prednisolone and prednisone are drugs of choice in pregnant patients requiring corticosteroid treatment. Corticosteroids do not increase the risk of congenital malformations. Possible adverse effects are perinatal infection and adrenal insufficiency in the newborn. Both events are only rarely reported in the literature, which comprises information on more than 1000 pregnancies. The clinical experience on the effect of slow-acting antirheumatic drugs (SAARDs) on pregnancy is insufficient to draw substantial conclusions. Available data from the literature give no clear evidence of an increased risk of teratogenicity for any of these drugs. Rheumatologists differ in their view on the advisability of using SAARDs during pregnancy. Hydroxychloroquine, which is regarded as less toxic than chloroquine, is recommended by some rheumatologists for the treatment of pregnant patients with active systemic lupus erythematosus (SLE) or rheumatoid arthritis. Sulfasalazine can be continued during pregnancy. Data on gold compounds and penicillamine are sparse and inconclusive. A reasonable approach is to stop these agents as soon as pregnancy is confirmed. The limited experience with cyclosporin has been obtained when the drug was used to prevent allograft rejection. Further data regarding the use of this drug in pregnant patients with rheumatic diseases are needed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7882640 TI - Techniques for early diagnosis of the abnormal fetus. AB - The phenomenal developments in molecular genetics and technological refinements which have occurred over the past decade are revolutionizing the area of prenatal genetics. State-of-the-art care commences with comprehensive preconceptional counseling. Prenatal diagnosis is now feasible from the moment of conception onward. Imaging techniques have allowed non-invasive diagnosis while minimally invasive techniques concentrate on sampling maternal blood for fetal cells or markers of feto-placental metabolism. Invasive techniques are rapidly expanding and becoming safer, comprising of chorionic villus sampling, early amniocentesis, midtrimester amniocentesis as well as very early fetoscopy and umbilical vein sampling. PMID- 7882641 TI - The role of cordocentesis in the diagnosis of fetal well-being. AB - One of the most important parameters that any antenatal testing technique is measured against is the fetal acid-base balance. Cordocentesis is a relatively safe invasive method that can be used to evaluate the fetal acid-base status directly. The knowledge of these parameters is always invaluable under research conditions and, in select instances, can contribute significantly to clinical management. PMID- 7882636 TI - Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti inflammatory drugs. AB - The nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly prescribed, especially in the elderly population. In many countries more than 10 different NSAIDs are available. As the older pyrazole compounds like phenylbutazone, oxyphenbutazone and azapropazone are most prone to pharmacokinetic interactions, the use of these compounds should be avoided where possible. Acidic NSAIDs interact with bile acid-binding resins, resulting in decreased concentrations of NSAIDs in the blood. In earlier reports it was suggested that the absorption of NSAIDs was affected by antacids and sucralfate. More recently, it was shown that there is delayed absorption of these drugs, but there is no difference in the extent of absorption. Only salicylates had their urinary secretion enhanced by antacids, which increase the urinary pH to values > 7. Histamine H2-receptor antagonists can be combined safely with NSAIDs. The concomitant administration of probenecid increased the blood concentration of NSAIDs, so an enhanced anti inflammatory effect can be expected when these 2 drugs are combined. More importantly, NSAIDs can cause pharmacokinetic drug-drug interactions with other drugs. As can be expected, interactions with drugs that have a small therapeutic window are most likely to be of clinical significance. For example, lithium, medium to high dose methotrexate and, to a lesser extent, cyclosporin may be affected by concomitant administration of an NSAID. Aspirin (acetylsalicylic acid) and/or pyrazoles interact with oral anticoagulants, oral antihyperglycaemic agents and the anticonvulsants phenytoin and valproic acid (sodium valproate). Elevation of blood concentrations of these agents can be potentially dangerous. Similarly, NSAIDs interact with digoxin. This interaction is most likely to occur in the elderly, in neonates or in patients with renal impairment. Indomethacin can influence the blood concentrations of aminoglycosides in neonates. Unfortunately, this effect seems unpredictable, so practical therapeutic recommendations cannot be made. When NSAIDs are combined with salicylates or diflunisal, the blood concentrations of the salicylate or diflunisal may increase. However, the clinical relevance of this increase in drug concentration seems to be of minor importance. Gastrointestinal bleeding caused by NSAIDs is the most dangerous when it results from a mixed pharmacokinetic/pharmacodynamic interaction; however, patients are also at risk when pharmacodynamic interactions only are involved. PMID- 7882642 TI - Maternal perception and Doppler detection of fetal movement. AB - Fetal movement can be used as a tool for assessment of prenatal well-being. Maternal perception of fetal movement, using a formal graphic "count-to-ten" system is often used as an adjunct in high risk and normal pregnancies. Doppler detection of fetal movement is a newly introduced, easy to perform methodology. Identification of coupling fetal heart rate accelerations to fetal movement as an aid for nonstress testing and recognition of fetal behavior, fetal behavioral states and cycling between states, is a current clinical application of this new technique. PMID- 7882643 TI - The nonstress test. Reassessment of the "gold standard". AB - The NST is simpler, less invasive, less time-consuming, and less expensive than its predecessor, the CST. It may be conducted in the outpatient setting with less skilled personnel. If the NST is to remain an important diagnostic modality, the issues of interpretative criteria, test conditions, and population composition must be reconsidered. In the future, authors must specify these data in detail and present their parameters of sensitivity, specificity, predictive values, and prevalence clearly. They also would be well advised to consider the value of adding other FHR information, such as baseline rate and variability to their interpretative criteria. Because clinical management--i.e., whether or not to intervene--may be influenced by or directly follow the outcome of an NST, it is even more important that such critical questions be addressed. The testing process should be cost effective, accurate, and sensitive enough to detect pregnancies at risk, yet specific enough to identify pregnancies that will have a good outcome. We believe that the issue of stand-alone NSTs should be examined for all indications and gestational ages commonly encountered. In our laboratory, current practice suggests that most conditions, at most gestational ages, benefit from an approach that combines the NST with amniotic fluid assessment and that uses age-adjusted standards to avoid misclassification of normal infants. PMID- 7882644 TI - Vibroacoustic stimulation for risk assessment. AB - VAS of the human fetus produces a profound alteration of fetal behavior and FHR. Many authors have reported on the success of the technique in improving the efficiency of antepartum FHR testing without altering the predictive reliability of the tests. VAS has other potential advantages in the antepartum assessment of fetal well-being and provocation of fetal activity to improve ultrasonographic anatomic visualization. Experimentally, VAS offers a unique opportunity to assess how the fetus responds to its external environment. The information currently available suggests that exposure of the fetus to VAS is safe in its present clinical applications. Additional investigation is needed to characterize the best frequency, duration, intensity, and choice of stimulus to provide the most consistent responses. The literature to date presents a confusing array of studies that have used different methodologies, making comparisons of studies difficult. It is the opinion of the author that VAS is a safe clinical technique as currently employed. PMID- 7882645 TI - Amniotic fluid assessment. Methods and role in fetal assessment. AB - AFV assessment by one method or another has become an adjunct to nonstress testing in most pregnancies requiring surveillance. Evaluation by nonstress test and amniotic fluid assessment for fetuses with maternal risk factors in a protocol such as that outlined by Devoe is common practice. Adaptation of that algorithm (Fig. 4) to the needs of the clinical setting are simple. Quantitative and nonquantitative methods show an increase in perinatal morbidity and mortality with abnormal values. Those trends are most evident in studies involving postdate gestations, such as those by Marks and Lagrew. The literature and its applied lessons for clinical practice are confused by the many variables considered by those investigating AFV assessment. Superiority of one method over another has not been demonstrated consistently from one study to the next. The good correlation in AFV estimated by ultrasonography and determined by dye-dilution techniques is still based on limited studies that are unlikely to be replicated soon because of the invasive nature of the test. Even in the best circumstances, errors at extremes of AFV are common with the use of ultrasonography. At present, the best recommendations from the literature seem to take two main directions. Antenatal testing of the fetus at risk should include some evaluation of AFV. The fetus with apparently abnormal AFV should be studied anatomically and considered for delivery if decreased AFV is associated with other test abnormalities--i.e., a nonreactive nonstress test. PMID- 7882646 TI - Multiple parameter biophysical testing in the prediction of fetal acid-base status. AB - Available data on the relationship of multiple parameter biophysical testing and fetal acid-base status suggest that a nonreactive nonstress test and absent fetal breathing are the first manifestations of fetal compromise, whereas absent body movement and tone are associated with more advanced degrees of fetal compromise. PMID- 7882647 TI - Doppler velocimetry. Where does it belong in evaluation of fetal status? AB - Doppler velocimetry is very useful as an antepartum surveillance tool that is able to detect pathologies of the fetus and predict the development of acidosis and hypoxia. Appropriate use can help us to decrease the mortality and morbidity in identifying earlier compromised fetuses. PMID- 7882648 TI - Automated methods of fetal assessment. The future of antenatal testing. AB - Conventional approaches to antenatal assessment require considerable input from domain experts to provide their maximum benefit. Many of the tests commonly used suffer from inter- or intraobserver errors, lack of objectivity and reproducibility, and inappropriate application by less experienced personnel. Recent developments in computer-assisted analyses of fetal heart rate testing and biophysical testing are presented to address some of these concerns. The development and validation of expert systems which address the use of domain knowledge to improve diagnostic, prognostic, and therapeutic approaches to antenatal management are described. Future areas of investigation are suggested. PMID- 7882649 TI - Labor admission test. AB - The Labor Admission Test permits the clinician to reallocate risk patients based on their admission fetal heart rate pattern. This means that obstetric patients normally considered high risk on admission to labor and delivery can be reallocated to low risk when the initial fetal heart rate pattern is reactive. PMID- 7882651 TI - The diagnosis and management of urinary incontinence in women. PMID- 7882650 TI - Male erectile dysfunction assessment and treatment options. AB - Until the early 1970s impotence was believed to be primarily a psychological disorder. The treatment usually consisted of empiric testosterone administration and psychotherapy, that were often ineffective. The introduction in the early 1970s of penile implants changed the treatment options and at the same time ushered in the modern era of male sexual medicine. Clinical as well as laboratory research improved significantly the diagnosis and treatment options of the impotent man. Today the man with a sexual problem has a much better chance of proper diagnosis and effective treatment. PMID- 7882652 TI - Current considerations in the diagnosis and initial treatment of testicular cancer. PMID- 7882653 TI - Complications of bacillus Calmette-Guerin (BCG) immunotherapy in superficial bladder cancer. PMID- 7882654 TI - Use of dental hygienists and returns to scale in child dental care in Norway. AB - The purpose of this study was to investigate, in the provision of dental care for children, technically and economically efficient combinations of dentists and dental hygienists and to study returns to scale by analyzing production functions. Data from 137 dental health clinics were analyzed. Output was registered as the number of 3-18-yr-old children to whom the clinic delivered complete dental care. Resource input was registered as hours spent by dentists, dental hygienists and dental assistants to deliver care to the children. The average clinic that employed dental hygienists used one hygienist hour per three dentist hours for child dental care. It would save dentist time, but not costs, to extent the use of hygienists. Increased use of dental hygienists might be economically efficient if the work distribution between the personnel groups were changed, for example, by delegating more examinations and preventive care to hygienists. There were technical opportunities for further substitution of dental hygienists for dentists both by introducing dental hygienists in the clinics that only used dentists in child dental care and by extending use of hygienists in clinics that already employed hygienists. This study found no productivity gain from centralizing treatment of children in large dental clinics. PMID- 7882655 TI - Comparison of two indices of dental fluorosis in low, moderate and high fluorosis Tanzanian populations. AB - This study aimed at comparing the Thylstrup-Fejerskov index (TFI) and the Dean's Index (DI) which were applied on three communities with different severity of dental fluorosis. A total of 1565 children aged between 11 and 18 yr with a mean age of 14.7 were examined for dental fluorosis with the TFI and 1155 of these children were also examined with the DI. The measurement error for the TFI was 0.50 (10 scale point) compared to 0.53 for DI (6 scale point). The Kappa values and the measurement-remeasurement correlation appeared to be better for the TFI. No difficulties were encountered in applying the TFI in contrast to the DI, which caused uncertainties in assessing the "questionable" and "very mild" scores, and this may explain the relatively better reproducibility of the TFI. The correspondence between both indices was determined. TFI 0 corresponded well with DI 0. The conversion values for TFI 1, 2, 3 and 4 into DI scores were 0.3, 0.8, 1.4 and 2.4 respectively. The TFI 5-9 corresponded with DI score 4. TFI could discriminate the severe forms of dental fluorosis which were categorized in Dean's highest score 4. TFI was able to reveal more dental fluorosis than DI in communities with minor and moderate dental fluorosis. In the community with severe dental fluorosis where more than 85% of all teeth exhibited a DI > or = 1, both indices revealed a comparable prevalence of dental fluorosis. The TFI is considered a near ideal instrument. PMID- 7882656 TI - Caries development after substitution of supervised fluoride rinses and toothbrushings by unsupervised use of fluoride toothpaste. AB - In a nonfluoridated community of Finland, where fortnightly fluoride rinsing with 0.2% sodium fluoride has been used for nearly two decades, a total of 313 children 7-8 yr old were recruited and randomly divided into two groups. 206 children completed the 3-yr trial. The control group (n = 94) participated in the rinsing program which included supervised toothbrushings, while the test group (n = 112) received a new fluoride toothpaste tube (0.15% F) for home use every second month. Annual dental recordings, treatment plannings and the treatment itself were all carried out by one clinician. At the end of the study the number of caries-free children of the toothpaste group was lower (P < 0.01) and the caries increment higher (P < 0.05) than that of the mouthrinse group. Out of the mean of four dental visits per child and year some 1.5 were prophylactic by nature. No differences were found between the number of treatment visits, time or prophylactic care of the two groups. Unsupervised use of fluoride toothpaste may not be a sufficient substitute for the school-based fortnightly fluoride rinses and supervised toothbrushings in caries prevention of children with erupting permanent teeth. PMID- 7882657 TI - Subjectively reported oral health status in an adult population. AB - This study describes the subjectively reported oral health status of an adult population aged 18 yr and over. The study used measures of the functional, social and psychological impact of oral disorders, originally developed for surveys of older adults, and aimed to determine whether or not they were sensitive to the oral health concerns of younger adults. It compared four age groups (18-29 yr; 30 49 yr; 50-64 yr; 65 yr and over) in terms of the following subjective oral health indicators: ability to chew, problems speaking, oral and facial pain; other oral symptoms; problems eating; problems with communication-social relations; limitations in activities of daily living and worry and concern. The initial hypothesis that few younger subjects would report the kinds of problems documented by these indicators was not supported. On all measures except ability to chew, younger subjects were as likely to be compromised by oral conditions as older subjects. PMID- 7882658 TI - Dental status, diet and cardiovascular risk factors in middle-aged people in northern Sweden. AB - The aim of the present study was to compare the dietary intake and the levels of traditional cardiovascular (CVD) risk factors in edentulous middle-aged individuals and individuals of the same age and sex who still had natural teeth. The study was performed within the framework of the MONICA-project. Population registers were used to sample randomly 1287 men and 1330 women aged 25-64 yr. Data were collected from a mailed questionnaire, blood analyses, registrations of blood pressure and anthropometric measures. The estimated daily energy intake did not differ between the two groups, but edentulous men and women ate more sweet snacks compared to those who still had teeth. Edentulous men also ate less fruits, vegetables and fibre and edentulous women ate more fat than dentates. Edentulous men and women were more obese and had lower serum HDL-cholesterol concentrations than those with remaining teeth. Edentulous women also had significantly higher concentrations of total cholesterol and triglycerides in serum than dentate women. Edentulous men and women were more often regular smokers, but not snuff users, than dentates of the same age and sex. Thus, the presence of two or more cardiovascular risk factors was more common in edentulous individuals than in those who still had natural teeth. In summary, these results support the hypothesis that edentulous middle-aged individuals have a more unfavourable risk factor profile for CVD. Counselling on balanced dietary habits and non-smoking given by dental personnel to orally diseased patients- recommendations given to improve resistance to dental caries or periodontitis- might therefore improve general health and possibly also improve risk factors for CVD. PMID- 7882659 TI - Perceived, desired, and normatively determined orthodontic treatment needs in male US Army recruits. AB - This study assessed perceived, desired, and normative need for orthodontic care in a systematic random sample of 576 male enlisted Army recruits at one Army post in fall 1990. Perceived and desired need were collected using a pretested questionnaire. Normative need was assessed on all participants by one dentist using the Treatment Priority Index. Results show 16.3% of enlisted male Army recruits have severe or handicapping malocclusions, yet only one-third desire corrective treatment. Preference for orthodontic care is strongly influenced by the recruit's education level. We recommend that military health policymakers consider expanding access to adult orthodontic care for active duty military personnel to keep pace with its widening acceptance by the general public and to keep the military health benefits package competitive with those of civilian employers. PMID- 7882660 TI - Evaluation of a continuing education intervention "Periodontics in General Practice". AB - Evidence exists that some dentists may be failing to perform adequate periodontal diagnostic and preventive care for their patients. Continuing education (CE) is an avenue that is frequently employed as a strategy to alter the style of practice. This paper presents an evaluation of a year-long continuing education intervention "Periodontics in General Practice", conducted among randomly selected private general dental practices in Adelaide, South Australia. The CE intervention featured a 1-day seminar, bi-monthly newsletters, individualised 3 monthly comparative feedback, and technical assistance. The study employed a longitudinal quasi-experimental design, which allowed for evaluation of the effectiveness of the intervention among practices employing hygienists (n = 12) and not employing dental hygienists (n = 12), taking into account the covariates of baseline level of provision of periodontal services, the practice's level of participation in the intervention and attendance at other CE courses in periodontics over the year. A comparison group of practice (n = 12) did not participate in the intervention over the year. Patient record audits, conducted at baseline and at 12 months, provided data for the evaluation of the effect of the intervention on the recording of periodontal diagnostic, preventive and treatment items. Practices participating in the intervention showed increases in the percentage of records containing at least one periodontal diagnostic notation, and those practices employing hygienists showed an increase in the percentage of records with at least one preventive notation and one treatment item.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882661 TI - A meta-analysis of durability data on conventional fixed bridges. AB - A meta-analysis was performed on the dental literature since 1970, presenting clinical data of conventional bridges. 42 publications were found that contained durability data of conventional fixed bridges. These publications dealt with 33 different samples. According to the exclusion criteria 26 studies were excluded for the meta-analysis. The data of 4118 conventional bridges were analyzed. The calculated overall survival rate was 74.0 +/- 2.1% after 15 yr. PMID- 7882662 TI - Survival and retreatment need of abutment teeth in patients with overdentures: a retrospective study. AB - The retreatment need was assessed in 148 patients wearing 125 overdentures in the mandible and 56 in the maxilla. The total number of abutment teeth was 512. During the evaluation period 44 abutments were extracted. The endpoints of the survival analysis after 6 yr were 89%, taking the loss of all abutments as the failure criterion for overdentures. During the clinical examination it was found that 31% of the abutments needed treatment while the retrospective part showed a mean yearly restoration need of 17.5%. Caries was the most important reason for retreatment. These data demonstrated that patients with overdentures should be regarded as high risk patients for retreatment of abutments. Therefore a stringent maintenance program, including regular recall appointments and the application of a preventive regimen, is desirable. PMID- 7882663 TI - Prediction of the need for bitewing radiography in detecting caries in the primary dentition. AB - In recent literature some controversy has been reported regarding the prescription of bitewing radiography for caries diagnosis, particularly in children. While the low prevalence of caries justified the decision not to take radiographs, it has also been reported that the benefits of detecting slowly progressing, clinically undetectable lesions could outweigh the "costs" of radiography. It was the aim of this study to investigate whether specific risk factors could predict the presence of additional dentinal lesions (ADL) in the primary dentition on radiographs which could not be detected by visual inspection. Bitewing radiographs were taken in 182 children aged 5 yr. Risk factors for ADL were identified and appropriate rating scales were designed. Sensitivities, specificities and relative risks expressing the relation between scale values and ADL were computed for each of the risk factors and direct and stepwise discriminant analyses were performed. The results indicate that particularly the presence of lactobacilli and mutans streptococci in saliva and the detection of three or more discolored enamel lesions or dentinal lesions were good predictors of ADL. It is suggested that these risk factors be used in the timing of bitewing radiography in children with a primary dentition. PMID- 7882664 TI - Influence of exposure to various fluoride technologies on the prevalence of dental fluorosis. AB - An increase in the prevalence of dental fluorosis among children in North America is well documented. Published reports of the relationship between the occurrence of dental fluorosis and early exposure to various fluorides and the use of different types of infant feeding practices have begun to provide insights into possible causes for this increase. This study was designed to investigate this issue for children living in a non-fluoridated and a fluoridated community in British Columbia, Canada. Parents or guardians completed a questionnaire which detailed exposure to different types of fluorides and infant feeding practices during the first 6 yr of life. Completed questionnaires were returned and examinations were performed on 1131 children. 60% of children had dental fluorosis, and only 8% presented with scores of 2 or greater. Logistic regression analyses showed that the use of infant formula and parental educational attainment were significantly associated with the occurrence of dental fluorosis in the range of scores from 2 to 6. Despite these statistically significant findings, these variables actually had little additional predictive value beyond a chance occurrence in determining which children would have dental fluorosis. PMID- 7882665 TI - Dental caries prevalence in a group of schoolchildren in Wuhan City, PR China, 1993. PMID- 7882666 TI - AIDS. PMID- 7882667 TI - The component-based architecture of the HELIOS medical software engineering environment. AB - The constitution of highly integrated health information networks and the growth of multimedia technologies raise new challenges for the development of medical applications. We describe in this paper the general architecture of the HELIOS medical software engineering environment devoted to the development and maintenance of multimedia distributed medical applications. HELIOS is made of a set of software components, federated by a communication channel called the HELIOS Unification Bus. The HELIOS kernel includes three main components, the Analysis-Design and Environment, the Object Information System and the Interface Manager. HELIOS services consist in a collection of toolkits providing the necessary facilities to medical application developers. They include Image Related services, a Natural Language Processor, a Decision Support System and Connection services. The project gives special attention to both object-oriented approaches and software re-usability that are considered crucial steps towards the development of more reliable, coherent and integrated applications. PMID- 7882668 TI - Multimedia as part of the HELIOS SEE. AB - This paper discusses the approach taken in HELIOS towards defining a distributed multimedia component as part of the HELIOS Software Engineering Environment (SEE). A user requirements study, performed at the beginning of this project, led to a functional distinction between permanent kernel components and optional service components. The multimedia components cover audio and video capture, replay and synchronization. Medical imaging is considered as a separate service, developed by the German partner of the HELIOS consortium. PMID- 7882669 TI - The HELIOS Medical Connection Services. AB - This paper presents the design and implementation of the HELIOS software component that deals with integration of medical applications in health information networks. The problem of interoperability between health information systems based on different data exchange syntaxes is first discussed. A meta model, relying on CEN TC251 recommendations, is then presented as a possible solution to this problem and a message description language including these recommendations is proposed. Using this meta-model, the Medical Connection Services that comprises a generic message processing automaton, a resource manager and a mapper is able either to interpret messages expressed in a given syntax (e.g., EDIFACT, ASTM) and map them to the application objects or to automate the translation of the messages in another syntax. Special focus is given on the position of the Medical Connection Services within the HELIOS integration strategy (i.e., through data, presentation and communication). The problem of semantic heterogeneity is then discussed. PMID- 7882670 TI - ARTEMIS-2: an application development experiment with the HELIOS environment. AB - A medical application is a highly complex system that embraces many data types and a very large number of data processing functions and methods. The development of integrated software engineering environments has deeply changed the conception of applications and the profile of the application developers. In this paper, we address the problem of the development process of a specific multimedia application, called ARTEMIS, within the distributed HELIOS environment. The application is intended to manage information about hypertensive patients, in particular, retrieval and display of administrative, clinical and biological data and display and analysis of digital angiography images and medical reports. The objective is to show how the developer can use, customize and organize the services HELIOS provides. A particular focus is set on reuse strategies and integration during the development process. A scenario has been realized and illustrates the current state of the application. The discussion focuses on the advantages of such distributed environments in medical application development. PMID- 7882671 TI - The HELIOS Unification Bus: a toolbox to develop client/server applications. AB - In the medical domain, new developments commonly rely on client/server architectures. But face to distributed environments, the software developers encounter a tremendously increasing complexity when building integrated applications. This paper presents the HELIOS Unification Bus (HUB), a communication integration framework for the HELIOS medical software engineering environment that allows the exchange of data between components that can be hosted on heterogeneous machines linked by a network. The HUB is developed as a C++ toolbox over UNIX and TCP/IP. It includes a message routing entity called router and a generic application programming interface (API), implemented as a C++ library, that allows to build easily software components compliant with the standardised HELIOS language. Messages conveyed by the bus are composite objects that are serialized to be transmitted over the bus using the ASN.1 ISO presentation protocol. The article describes the use of the bus to ease the development and execution of distributed medical applications and its role from the communication integration standpoint. PMID- 7882672 TI - Documentation and information services in the HELIOS project. AB - In a modern software project large amounts of documentation is produced. All parts of the complex software system require extensive documentation--both for reference purposes and promotional reasons. However, there are some aspects that often are forgotten or badly implemented; (i) the availability of on-line documentation, (ii) integration of the different formats of documentation, and (iii) the world wide promotional aspect. To solve these problems, the Helios project has chosen to integrate its public documentation and software material into a hypertext system using the World Wide Web. PMID- 7882673 TI - Analysing and developing object-oriented medical applications with HELIOS. AB - The HELIOS project promotes systematic reuse of existing software in a valuable methodological context. In order to reach this goal, the Analysis and Design Development Environment (ADDE) has been realized as a HELIOS component. This component includes the Analysis and Design sub-component (ADT), which supports the Rumbaugh's object-oriented methodology and the Insertion Retrieval Tool (IRT), which implements the reuse. The ADT sub-component enhances the quality of software development permitting a correct analysis, and design and a satisfactory documentation. The IRT Tool is dedicated to reuse by retrieving parts of existing applications (retrieve) and by qualifying elements just created or updated (insertion). A faceted system adapted to the medical domain allows an efficient search among the object database. Both tools contribute to reducing the cost of software development. This paper presents the design and the implementation of these tools in the HELIOS framework. PMID- 7882674 TI - A reuse oriented Development Database: the HELIOS Object Information System. AB - This paper describes the Development Database of a Software Engineering Environment (SEE), that couples reuse and object-oriented technologies. We propose a classification model for the repository of reusable components that is a support for an efficient retrieval mechanism, and a reusable component model that considers components of large and low-granularity levels (e.g., application frameworks and methods of a given class). The reusable component model is based on the underlying idea that development components are not operational components since they do not have the same purpose. This model first represents each component as an aggregation of other sub-components, together with all information needed for its retrieval (e.g., classification and facets), its under standing (e.g., informal functional description) and its dependencies with other development components, in particular the applications in which it occurs, since applications are considered also as abstract development components. This approach was tested thanks to an existing application which was loaded into the SEE. From that moment, it was possible to regenerate a new application in a reasonably short time. Moreover, the existence of a retrieval tool permits to validate the development components classification, but also put forward the importance of the qualification step. In particular, the versioning should be carefully processed. Furthermore the fact that all the development objects are built on an homogeneous model allows easier tools management and interapplication reusability. PMID- 7882675 TI - Usability and efficiency. The HELIOS approach to development of user interfaces. AB - This paper describes the user interface related services of the HELIOS project. The design and implementation of efficient user interfaces is a prerequisite for successful introduction of computer support in health care ward units. Design principles must be based on a basic understanding of cognitive aspects of human computer interaction, as well as on detailed knowledge about the specific needs and requirements of the health care professionals. In the HELIOS project, a style guide for design of user interfaces has been developed. The style guide defines detailed design guide-lines together with a set of interface elements specified for the ward domain. Development tools for construction and implementation of user interfaces to ward applications have been developed and integrated into the HELIOS SEE. The tools are based on the TeleUSE product, which has been extended and adjusted to the HELIOS specifications. A set of new widgets, designed to implement health care interface elements, has been incorporated into the development tool. PMID- 7882676 TI - The HELIOS Image Related Services. AB - The HELIOS Software Engineering Environment is a tool for the construction of medical ward information systems. This paper describes the image processing tools which are a part of this system. The Image Related Services can be used both as ready-to-use end-user tools and as software modules for the construction of integrated multimedia applications. The tasks and architecture of the end-user tools and their integration into the HELIOS architecture are described. It is shown how the available image processing functionality can be used to build up new applications. PMID- 7882677 TI - Natural language processing of medical texts within the HELIOS environment. AB - A large number of hospital applications are potentially interested in natural language processing since they currently heavily depend on an efficient use of a huge amount of textual information. The need for systems that are able to accept multiple European languages is of paramount interest, as language barriers can be a strong impediment for large-scale communication in Europe, in particular regarding telemedicine. In the context of the AIM project HELIOS, the Natural Language Processing (NLP) component offers a large variety of medical services according to natural language free input. It allows the multilingual analysis of medical texts (currently in English, French and German) and the storage of the meaning of these texts under a deep knowledge representation that can be queried whenever it is needed. In addition, it provides facilities to handle knowledge source embedded into the conceptual typologies and into the dictionaries. This article aims at describing all these functionalities and their integration into the environment of the HELIOS project. PMID- 7882678 TI - Data driven medical decision support based on Arden Syntax within the HELIOS environment. AB - Methods and tools for development of data driven decision support systems (DSSs) is an integral part of the HELIOS software engineering environment. The DSS development environment includes tools for knowledge acquisition and knowledge base construction, provides trigger mechanisms for evocation of the knowledge base and an inference engine for execution control of appropriate parts of the knowledge base during run-time. The tools are part of the HELIOS service components and are integrated within the HELIOS communication framework. The work is based on the Arden Syntax, a standard for knowledge representation, allowing medical logic modules (MLMs) to be shared and transferred between institutions. PMID- 7882679 TI - Cindy Rushton: big advocacy, little world. Interview by Michael Villaire. PMID- 7882681 TI - Trauma inflicted on critical care nurses. PMID- 7882682 TI - Cut bureaucracy, not caregivers, in healthcare reform. PMID- 7882680 TI - Patient education after valve surgery. PMID- 7882683 TI - Critical care nurse participation in ethical and work decisions. PMID- 7882684 TI - Midazolam for conscious sedation and surgery. PMID- 7882685 TI - The pharmacology column on midazolam. PMID- 7882686 TI - Midazolam for conscious sedation and surgery. PMID- 7882687 TI - The article on midazolam. PMID- 7882688 TI - Multiple organ failure syndrome. AB - Although many new areas of research are directed at the regulatory aspects of the metabolic response, the prognosis of MOF remains poor. Critical care nurses, challenged to provide a supportive environment during this life-threatening syndrome, must understand its onset, clinical patterns, and prolonged support required by patients. Such knowledge will enable critical care nurses to detect subtle changes while monitoring clinical status, and facilitate timely interventions in order to decrease the morbidity and mortality associated with MOF. PMID- 7882689 TI - The trauma nurse's role with families in crisis. AB - Trauma occurs suddenly and without warning, leaving the family ill-prepared to deal with the stressful event. Because this experience is often the first of its kind for the family, they may have no experience in dealing with these situations. Depending upon which member of the family is injured, a family's entire lifestyle could be disrupted, necessitating a shift in family roles and responsibilities. Previous coping skills are generally inadequate, and feelings of helplessness and powerlessness abound. The unknown time frame for recovery from the traumatic event is an additional stressor. Loss of the traditional family structure and inadequate support systems require that the trauma nurse be able to assist families of trauma victims in this time of crisis. To effectively support the family, the nurse must understand the impact of trauma and typical family responses to crisis. The key to effective management of these families is early assessment and appropriate intervention through providing information, active listening, facilitating flexibility in visiting, and family conferences. PMID- 7882690 TI - Management of an open abdominal wound with a synthetic covering. AB - The insertion of Silastic sheeting provides an opportunity for improved survival of patients with severe abdominal trauma. This new treatment modality represents a challenge to nurses to expand their knowledge base. PMID- 7882691 TI - Trauma case review: survival following impalement. AB - Prehospital care of patients with penetrating wounds must begin within minutes of the injury; definitive treatments should be initiated within an hour. Due to the advanced skills of the paramedics, nurses, doctors, and ancillary personnel, this patient arrived in the operating room within an hour of his accident. Fortunately, the impaled reinforcement rods missed the vital structures within the patient's thoracic and pleural cavities and spared his lower abdominal organs, vascular structures, and skeletal structures in his groin. This case study illustrates the importance of coordinated efforts in caring for this patient from the prehospital setting through the emergency department and operating room. PMID- 7882692 TI - The near-death experience following multiple trauma. AB - The NDE is a fascinating but not uncommon phenomenon that some trauma victims experience during physical crises or periods of apparent clinical death. When critical care trauma nurses are familiar with the characteristics of the experience, they are able to assist trauma victims to understand available information about NDEs. More important, critical care nurses are able to assist victims and their families to understand the meanings of the NDE and how it affects their lives. PMID- 7882693 TI - Multiple trauma with respiratory distress. PMID- 7882694 TI - Alcohol and trauma: the critical link. AB - The link between traumatic injury and alcohol consumption is strong. Although statistics vary, from one half to one third of trauma victims admitted to critical care units have an alcohol-related injury. The initial role of the critical care nurse is to identify the presence of alcohol by monitoring the patient's BAC. Once the presence of alcohol is confirmed, its effects impact directly on the plan of care that evolves during the critical illness. Nursing interventions focus on four specific areas affected by alcohol: the ability of alcohol to mask injury, the effects of alcohol on medications, alcohol withdrawal, and rehabilitation from alcoholism. By incorporating these four areas into the plan of care, the critical care nurse assists the patient not only to recover from a traumatic injury but also to deal with a problem drinking pattern. PMID- 7882695 TI - The patient-driven system. PMID- 7882696 TI - The tertiary nursing survey in the assessment of trauma patients: an important addendum to survival. PMID- 7882697 TI - A multi-centre study of the efficacy and safety of pravastatin in hypercholesterolaemic patients with non-insulin-dependent diabetes mellitus. AB - A multi-centre, non-randomized clinical study of 12-months' duration was performed in 112 patients with hyperlipidaemia associated with non-insulin dependent diabetes mellitus to evaluate the clinical efficacy and tolerability of pravastatin and to assess its effect on glycaemic control. Patients were eligible for this trial if they fulfilled the following criteria; a high plasma total cholesterol level greater than 220 mg/dl associated with stable glycaemic control for at least 3-months' observation period. On entry, patients received 10 mg pravastatin per day (5 mg twice daily) for 12 months. Clinical efficacy was evaluated in 108 patients. The results showed that pravastatin induced a significant decrease in serum cholesterol level mainly with LDL-cholesterol. Total cholesterol levels were decreased significantly from 275 +/- 3 mg/dl to 222 +/- 4 mg/dl within 3 months of the start of treatment, and LDL-cholesterol decreased from 192 +/- 4 mg/dl to 137 +/- 4 mg/dl. After 12 months' treatment, total cholesterol and LDL-cholesterol levels were 216 +/- 4 mg/dl (p < 0.001) and 137 +/- 5 mg/dl (p < 0.001), respectively. HDL-cholesterol levels were increased from 51 +/- 2 mg/dl to 56 +/- 2 mg/dl at 3 months (p < 0.001) and 55 +/- 2 mg/dl at 12 months (p < 0.01). Triglyceride concentrations were also decreased from 173 +/- 11 mg/dl to 156 +/- 13 mg/dl at 3 months and 137 +/- 10 mg/dl at 12 months (p < 0.01). Fasting plasma glucose and glycated haemoglobin levels were not affected by pravastatin. Adverse events observed in 5 cases were always mild and reversible. These results indicate a clinical usefulness of pravastatin with high compliance in patients with hyperlipidaemia associated with non-insulin-dependent diabetes mellitus. PMID- 7882699 TI - Evaluation of the effect of rifaximin in colon diverticular disease by means of lactulose hydrogen breath test. AB - To understand better the mechanism by which rifaximin produces symptomatic relief in diverticular disease of the colon, the effect of this antibiotic on orocaecal transit time and on the production of hydrogen by intestinal microflora after ingestion of lactulose was studied in 33 patients with this disease and in 11 healthy subjects. An hydrogen breath test was carried out to measure pulmonary hydrogen excreted during the 3 hours after ingestion of 10 g lactulose. In patients, the hydrogen breath test with lactulose was repeated after treatment with 400 mg rifaximin twice daily for 10 days. In patients under basal conditions and controls, orocaecal transit time did not differ significantly, but hydrogen production was significantly higher in the former (p < 0.02). In patients, transit time and hydrogen excretion in response to lactulose administration did not differ significantly before and after treatment with rifaximin, and these two parameters were inversely correlated both before (r = 0.49, p < 0.01) and after rifaximin (r = 0.58, p < 0.001). Fifteen of the 33 patients showed accelerated transit time after treatment with the antibiotic, 10 showed no variation, and 8 showed prolonged transit. In 19 patients a reduction in hydrogen production was noted after rifaximin, while in 14 an increase was demonstrated. Twenty-one of the 33 patients reported an improvement in their symptoms with rifaximin; of these, only 10 showed accelerated transit time and 9 a reduction in hydrogen production after rifaximin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882698 TI - Long-term thymopentin treatment in systemic scleroderma. AB - A study was carried out to investigate whether thymopentin treatment is capable of inducing changes in the immunological status of patients with systemic scleroderma and to compare any such changes with modifications in clinical condition. Nine patients were given thymopentin, 1 ml in 10 ml saline solution, by slow intravenous infusion 3-times weekly for 5 weeks (cycle). The cycles were repeated at 3-month intervals. Treatment duration ranged from 1 to 5 years. Blood samples were drawn at the beginning and at the end of each cycle and the patients' lymphocytic sub-populations were examined. A control group of 9 comparable healthy subjects were similarly tested. Data analysis showed that a statistically significant decrease of CD16+ and CD25+ lymphocytes compared to pretreatment was already apparent at the end of the first thymopentin treatment cycle. An improvement was found in the clinical condition of 7 of the 9 patients at the end of the follow-up period with a significant correction of unbalanced lymphocytic subsets. PMID- 7882700 TI - Herpes zoster: a comparative study of general practitioner and patient experience. AB - A study was carried out to compare attitudes, perceptions and experiences of general practitioners and patients who had treated/suffered from herpes zoster, or shingles, in the recent past. Randomized samples of 224 general practitioners and 236 patients were drawn from different locations in Italy, Germany and the United Kingdom, and interviews were undertaken as semi-structured face-to-face discussions with the subjects. Most of the discussion questions were the same for both samples but specifically targeted either towards the professional or the patient group. Analysis of the findings showed that although there was a high level of correlation between the two groups on opinions and attitudes on a number of issues, there were significant, important differences on others. For example, prodromal symptoms acknowledged by patients were not always recognized by general practitioners and there appeared to be an inability of some to diagnose early enough to take advantage of appropriate anti-viral therapy whilst they acknowledged the need to do so. This in turn led to a number of patients either not receiving specific therapy or having inadequate therapy. Similarly, whilst general practitioners mainly reflected the current medical view that shingles is a benign and self-limiting condition, patients tended to consider shingles and post-herpetic neuralgia as a painful and serious condition that adversely affected their quality of life and to a greater extent than appreciated by many doctors. The findings of the survey indicate that there is need for improved understanding of the disease and its effects by both doctors and patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882701 TI - A double-blind trial of captopril or bendrofluazide in newly diagnosed senile hypertension. AB - Hypertension is a major risk factor for stroke and heart disease in the elderly. Eighty-one hypertensive subjects with mild cognitive impairement, aged over 70 years, were drawn from a community screening programme and randomized to either 12.5 mg captopril twice daily or 2.5 mg bendrofluazide daily in a double-blind trial. Subjects were excluded if they had previously received antihypertensive treatment. The mean blood pressure was reduced from 193/101 mmHg to 154/87 mmHg by captopril and from 188/102 mmHg to 151/89 mmHg by bendrofluazide after 24 weeks; there was no significant difference between the two drugs. Seven subjects withdrew due to adverse events. Adverse events occurred more frequently during the 2-week placebo phase than during active treatment with either drug. The only significant detrimental changes in pre-existing conditions were in 3 subjects (2 captopril, 1 bendrofluazide) who were noted to have worsening of their cataracts. One subject on captopril and 4 subjects on bendrofluazide became hypokalaemic. The trial results support the use of captopril as an alternative to bendrofluazide as a first-line antihypertensive agent in the community for elderly people, but large studies are required to measure accurately effects on significant morbidity and mortality. PMID- 7882702 TI - Dosing of neuroleptics in elderly demented patients with aggressive and agitated behaviour: a double-blind study with zuclopenthixol. AB - A double-blind controlled trial was carried out in 73 hospitalized elderly patients to evaluate the effect of different low doses of the neuroleptic, zuclopenthixol, on behavioural disorders associated with dementia. Patients were randomized into four groups and received treatment for 4 weeks with fixed daily doses of 2 mg, 4 mg or 6 mg zuclopenthixol, or with a dose which could be increased from 4 mg to 20 mg daily. The dose could also be reduced if necessary. Fifty-four of the patients remained on the same daily dose throughout the study. The results of symptom assessments showed that there was a significant improvement from baseline scores in all of the dose groups and, with the exception of patients on 2 mg daily, this was evident after only 1 week of treatment. Although improvement was noted in all the symptoms evaluated, the best effect was achieved on aggressive behaviour, restlessness/agitation, sleep disorders, and shouts/torments others. Only a few, relatively mild side-effects were recorded and there was no increase in frequency with increasing doses. There was significant correlation between the serum concentration and the dose of zuclopenthixol used but not in connection to age and clinical efficacy. PMID- 7882703 TI - Investigation into the duration of action of sustained-release ibuprofen in osteoarthritis and rheumatoid arthritis. AB - The duration of action of sustained-release ibuprofen ('Brufen Retard') was investigated in a 14-day double-blind study involving 14 osteoarthritis and 10 rheumatoid arthritis patients. The recommended once-daily dosage of this preparation (1600 mg taken in the evening) provided effective control of arthritic symptoms for both patient groups, with significant overall improvements in pain and stiffness compared to baseline. Substitution of placebo for a single dose of the active treatment resulted in a trend towards worsening of pain and stiffness in the rheumatoid group; however, the only statistically significant change involved impaired quality of sleep (p = 0.03) during the night after placebo administration, over 24-hours after the previous dose of active medication. In this particular study, symptom control was also clearly achieved for the osteoarthritis patients, as this group showed no deterioration within the same period. The 24-hour clinical action underlying these findings is consistent with ibuprofen plasma profiles obtained with the sustained-release preparation in earlier pharmacokinetic studies. It is likely that the greater sensitivity of rheumatoid patients to withdrawal of a single day's active treatment in this study reflects a more severe inflammatory disease process than that of the osteoarthritis patients. PMID- 7882705 TI - Incidence of soft tissue sarcomas in adults. PMID- 7882704 TI - Breast conservation therapy for invasive carcinoma of the breast. PMID- 7882706 TI - Heterogeneity in malignant soft tissue tumors. PMID- 7882707 TI - Grading of soft tissue sarcomas: proposal for a reproducible, albeit limited scheme. PMID- 7882708 TI - Clinical management of soft tissue sarcomas. PMID- 7882709 TI - Fibrous tumors and tumor-like lesions of childhood: diagnosis, differential diagnosis, and prognosis. PMID- 7882710 TI - Malignant fibrous histiocytoma: a "fibrohistiocytic" or primitive, fibroblastic sarcoma. PMID- 7882711 TI - Recent advances in tumors of adipose tissue. PMID- 7882712 TI - Classification of rhabdomyosarcoma. PMID- 7882713 TI - Spindle cell rhabdomyosarcoma: histologic variant of embryonal rhabdomyosarcoma with association to favorable prognosis. PMID- 7882714 TI - Alveolar rhabdomyosarcoma: a prognostically unfavorable rhabdomyosarcoma type and its necessary distinction from embryonal rhabdomyosarcoma. PMID- 7882715 TI - Malignant peripheral neuroectodermal tumor. PMID- 7882716 TI - Soft tissue sarcomas in the Kiel Pediatric Tumor Registry. PMID- 7882718 TI - Malignant peripheral nerve sheath tumours. PMID- 7882717 TI - Leiomyosarcoma. PMID- 7882719 TI - Rare soft tissue sarcomas. PMID- 7882720 TI - Molecular biological aspects of soft tissue tumors. AB - In the preceding, the reader has hopefully developed an appreciation of the major malignant tumors to be encountered in somatic soft tissues in children, adolescents, and young adults. In aggregate, this group of tumors accounts for about 20% of cancer in this age group. Importantly, they are curable tumors when nonmetastatic at presentation, but therapy appropriate to prognosis and tumor responsiveness is highly dependent on precise diagnosis. The historical morphologic methods alone will not suffice for this purpose, but the anticipated rapid advent of molecular genetic diagnostic and prognostic methods should. Useful, practical, and rapid genetic tests, available in the same time frame as the routine histopathologic evaluation of these tumors, are likely to forever change the diagnosis and management of these tumors, individually and as a group. PMID- 7882721 TI - Characteristic chromosome abnormalities and karyotype profiles in soft tissue tumors. AB - Characteristic chromosome abnormalities and karyotype profiles are emerging for the soft tissue tumors. The notable findings are summarized in the Table 1. Within the broad range of solid tumors, it is certainly the soft tissue tumors in which the most spectacular success has occurred with regard to neoplasia associated chromosome abnormalities. Cytogenetic studies of soft tissue tumors have been encouraged by the early and growing supporting interest of pathologists and clinicians concerned with soft tissue tumors. However, when one considers the variety of types and subtypes of benign and malignant soft tissue tumors, the number that has been so far characterized by a specific chromosome change is still very small. But, as we attempt to demonstrate in this report, these data should be viewed as paradigms for the importance of cytogenetic investigations in solid tumors. Cytogenetic studies of solid tumors are of more than clinical interest. Cytogenetic studies allow molecular investigations of the chromosomal breakpoints. They allow the search to proceed for genes involved in the chromosomal changes, providing a better knowledge of the malignant transformation process. In addition, the fruits of the combined efforts in cytogenetic and molecular technologies, from which has come "molecular cytogenetics," will let us recognize more conveniently, more quickly and, hopefully, less expensively the well-characterized diagnostic chromosome markers in tumor cells. Thus, we may be able to reach the goal of incorporating cytogenetics into standard diagnostic procedures for solid tumors, as has been achieved with hematological malignancies. Molecular cytogenetics including fluorescent in situ hybridization (FISH) technology promises to bring soft tissue tumor cytogenetics into regular diagnostic armamentaria and concurrently speed research into the basis of soft tissue tumors. PMID- 7882722 TI - DNA ploidy in soft tissue tumors: an evaluation of the prognostic implications in the different tumor types. PMID- 7882724 TI - Detection of cytomegalovirus genome by in situ hybridization in paraffin embedded endomyocardial biopsy specimens of viral myocarditis. AB - Cytomegalovirus (CMV) genes were detected by in situ hybridization in 25 Chinese patients with viral myocarditis (VMC). The positive hybridization signals were found in cardiomyocytes (6 cases, 24%), capillary endothelial cells (4 cases, 16%) and interstitial cells (7 cases, 28%). The difference between VMC and control group (16 cases died of brain trauma and 10 cases of congenital heart diseases was statistically significant. There was no definite pathomorphological relationship between the detection of CMV genes and myocardial lesions. The results suggest that CMV infection may be one of the causes of myocarditis and chronic stimulation of the immune system induced by CMV may be a possible pathogenesis of this disease. PMID- 7882723 TI - Experimental study of chuanxiong on cerebrovascular hemodynamic parameters. AB - In the experimental rabbit arteriosclerosis, the change of the cerebrovascular hemodynamic parameters (CVHP) and the effect of Chuanxiong (CX) on CVHP were observed. In arteriosclerosis group (AS group), the mean flow (Qmean), mean velocity (Vmean), maximal velocity (Vmax) and minimal velocity (Vmin) of the carotid blood flow and cerebrovascular compliance for zero pressure (CO) were significantly decreased (P < 0.05, 0.01), but the values of cerebrovascular peripheral resistance (R) and characteristic impedance (Zc) were significantly increased (P < 0.05 and 0.01), and the value of R showed significant positive correlation with the extent of carotid lesions (P < 0.01). All indexes of CVHP of the Chuanxiong group (CX group) were close to and had no significant difference from those of the normal group (N group) but Qmean, Vmean, Vmin, CO and R were significantly better than those of the AS group (P < 0.05, 0.01). These results showed that CX can effectively improve cerebrovascular hemodynamics. PMID- 7882725 TI - Ultrastructural observation on macrophage-lymphocyte interactions in semen from Tripterygium wilfordii Hook.f. takers. AB - Sixty-nine specimens from Tripterygium Wilfordii Hook.f. (TWH) users were investigated by electron microscopy. No macrophages were demonstrated in the 21 specimens collected prior to the administration of TWH. However, it was found in 23 out of the 48 semen specimens obtained following the TWH administration. The macrophages were functionally active as shown by the presence of a large number of cytoplasmic processes and pseudopodia on the surface, and primary and secondary lysosomes in the cytoplasm. The macrophages phagocytized sperm debris and degenerated or dead spermatids with formation of specific phagosomes. Around those macrophages, lymphocytes were commonly noted. The cytoplasmic processes of the two cell types could come into contact or even fuse with each other, leading to tight junction-like structure; in some of the contacts, the plasma membranes were found dissolved so as to form direct cytoplasmic linkage. PMID- 7882726 TI - Role of transesophageal echocardiography in pre- and post-percutaneous balloon mitral valvuloplasty. AB - Transesophageal echocardiogram (TEE) was performed in 33 consecutive patients with both rheumatic mitral stenosis and chronic atrial fibrillation to evaluate the usefulness of this technique for the detection of left atrial thrombi, mitral regurgitation before percutaneous balloon mitral valvuloplasty and iatrogenic atrial septal defect after the procedure. TEE correctly identified thrombi in 10 (30%) patients and significant mitral regurgitation in 5 patients who underwent surgical intervention. The remaining 18 patients underwent percutaneous balloon mitral valvuloplasty without evidence of systemic embolic event and obtained adequate outcome. Transesophageal color doppler echocardiography demonstrated left-to-right shunting flow through atrial septum in 5 of 7(71%) patients 3 days after the procedure and repeated TEE in 2 of these 5 patients showed no shunting after 6 months. In conclusion, TEE plays a definite role in the selection of patients for balloon mitral valvuloplasty and assessment of iatrogenic atrial septal defect. PMID- 7882727 TI - A study of the cytotoxicity of malignant pleural effusion lymphocytes and LAK cells against autologous tumor cells. AB - The cytotoxicity of malignant pleural effusion lymphocytes (MPEL) against autologous tumor cells (ATC) were compared with that of peripheral blood lymphocytes (PBL). It was demonstrated that the cytotoxicity of PBL was higher than that of MPEL (P < 0.001), but the cytotoxicity and expansion of MPEL activated by rIL-2 was much higher than that of PBL activated by rIL-2 (LAK cells) (P < 0.001). This shows that local immune reaction of the pleural cavity of patients with malignant pleural effusion was in the state of suppression. MPEL activated are better effector cells than LAK cells in tumor adoptive immunotherapy. PMID- 7882728 TI - Study on alteration of white blood cell deformability of NIDDM patients and the influencing factors. AB - Microfiltration technique was used to measure white blood cell deformability (WCD) in one hundred and thirty patients with non-insulin-dependent diabetes mellitus (NIDDM or type II). It was found that WCD of the diabetics was significantly decreased compared with fifty controls (P < 0.01) and further reduced with the rise of levels of plasma fibrinogen (Fg), plasma lipid, hemoglobin Alc (HbAlc) and fasting blood glucose (FBG), and also with the increase of age, the duration of diabetes, and the reduction of plasma magnesium concentration. It was shown that the decrease of WCD in diabetes mellitus was closely related to the degree of metabolic disturbance of the failure of diabetic control. PMID- 7882729 TI - A study on the serum pregnancy zone protein levels in pregnant women and patients with gynecological tumors. AB - In this study, the serum levels of the pregnancy zone protein (PZP) were determined by PZP-single radial immunodiffusion in 708 cases of normal pregnancy, 207 with abnormal pregnancy and 188 with gynecological tumors. The results indicated that serum PZP levels in the normal pregnancy was detectable 5 weeks after gestation. It increased with the advance of gestational weeks, and reached a peak level in week 40. The serum PZP levels in 81.7% of patients with threatened abortion but not aborted were within the normal range, and also mostly in those with pregnancy-induced hypertension, intrauterine growth retardation (IUGR), anencephalus and ectopic pregnancy; the serum PZP levels in 51.6% of patients with invasive moles and 80.0% with choriocarcinoma, respectively, were lower than in normal controls. In gynaecological tumors, the serum PZP levels were significantly higher in patients with ovarian carcinomas than in those with other ovarian tumors (P < 0.01), and in those with endometrial or cervical carcinoma than in those with uterine myomas (P < 0.01). These results suggest that measuring the serum PZP levels may be used as an important reference index to observe threatened abortion and to identify trophoblastic diseases and gynecological tumors. PMID- 7882730 TI - Long-term immunogenicity and efficacy of recombinant yeast derived hepatitis B vaccine for interruption of mother-infant transmission of hepatitis B virus. AB - Recombinant DNA Yeast-Derived Hepatitis B Vaccine (RYHB vaccine) is comparable to and can replace Plasma-Derived Hepatitis B Vaccine (PHB vaccine) for the prevention of mother-infant transmission of hepatitis B virus (HBV), but the duration of immune efficacy of RYHB vaccine is not clear. This study indicates the long-term efficacy for the prevention of mother-infant transmission of HBV. One hundred and six neonates born to HBsAg-carrier mothers with HBeAg positive were randomly divided into two groups, one receiving 20 micrograms per dose of RYHB vaccine and the another receiving 20 micrograms per dose of PHB vaccine on the day of birth, at 1 month and at 6 months (three times). Physical examination and blood tests were performed for all infants at 6, 12, 24, 36, 48 and 60 months of age. The results showed that the protective efficacies at 6, 12, 24, 36, 48 and 60 months were 67%, 75%, 63%, 62%, 57% and 56%, respectively for the RYHB vaccine group and 58%, 76%, 51%, 41%, 24% and 18%, respectively for the PHB vaccine group. The protective efficacy was notably significant in the last two years. The study indicates that the duration of protective efficacy is over 5 years with RYHB vaccine, being longer than that of PHB vaccine. These recipients of RYHB vaccine showed no side effects, and the vaccine is regarded as safe and effective. PMID- 7882731 TI - Surgical management of the hypopharyngeal and cervical esophageal cancer. AB - Between December 1979 and December 1992, 15 patients with hypopharyngeal and cervical esophageal cancer were treated surgically. Total pharyngolaryngectomy and partial cervical esophagectomy were performed and the defects were reconstructed with cervical skin flaps in 2 cases. The free jejunal segments were used in 6 cases following total pharyngolaryngectomy and cervical esophagectomy, cervical esophagectomy (larynx preserved) was repaired with free jejunal graft in 1 case. The pharyngogastric anastomosis following total pharyngolaryngoesophagectomy were performed in 4 cases, one of them, used pectoralis major myocutaneous flap for resection of soft tissue and skin of the neck. The pectoralis major myocutaneous flap and forearm free flap in 1 case respectively were used to reconstruct the deficits of total laryngectomy and partial pharyngectomy, and partial pharyngolaryngectomy. In our series, 1, 3, 5 years survival rates were 73.3% (11/15), 50% (6/12) and 55.6% (5/9), respectively. The advantages and disadvantages of a variety of operative procedures and the cervical lymph nodes management will be discussed. PMID- 7882732 TI - Correlative study on findings of dynamic myelography and surgical operation in non-bony lumbar spinal canal stenosis. AB - The authors performed dynamic lumbar myelography with Omnipaque on 110 patients from 1990 to 1992, of them, 33 cases were diagnosed as non-bony lumbar spinal canal stenosis according to contrast medium defect seen on the lateral view of the myelogram. All such cases were operated on and their dynamic pathological findings during the operation were recorded to compare with the abnormal findings observed on the myelograms, there was a high coincidence rate of 88.7%. The authors believe that the fibrous degenerative changes make up the basis of dural sac compression and the dynamic compression in the spinal canal plays a very important role in causing the severity of the stenosis. As the dynamic pathological findings on the myelograms can not be well demonstrated on CT scanning and MR imaging, the dynamic lumbar myelography should be the method of choice for use in some cases. PMID- 7882733 TI - Effect of internal fixation plates on microcirculation in under-plate cortical bones. Microangiography and scanning electronmicroscopy. AB - To elucidate the effect of the internal fixation plates on the local bone blood supply, we used microangiography and scanning electron microscopy to observe the morphological changes of microcirculation in the cortical bones obtained from intact rabbit tibiae on which plates of two different stiffness had been fixed for comparison. The results indicated that both rigid stainless steel plate and less rigid methyl methacrylate plate could induce the bone microcirculation under the plate to undergo a process from early depression to late reactive recruitment. The features of the microcirculation recruitment such as vascular number, arrangement and dilatation varied with plates of different stiffness and were more obvious in the cortex fixed by rigid stainless steel plate. PMID- 7882736 TI - [Treatment of unstable angina pectoris]. PMID- 7882734 TI - Saturation diving with heliox to 350 meters. Observation on hearing threshold, brainstem evoked response and acoustic impedance. AB - Four divers were compressed to 350 m to observe changes in hearing threshold, brainstem evoked response and acoustic impedance. The divers experienced no tinnitus, impairment of hearing, earache during compression. Examination showed that the threshold of lower frequency range of hearing was elevated because of the masking effect of the noise in the hyperbaric chamber. Changes in waveform and latency of brainstem evoked response were due to changes in sound wave transmission affected by the chamber pressure and a poor ratio of signal to noise in the hyperbaric environment with heliox. All these changes were transient. After leaving the chamber, the hearing threshold and brainstem evoked response returned to normal. Besides, there were no changes in tympanogram, acoustic compliance and stapedius reflex before and after diving. This indicated the designed speed of compression and decompression in the experiment caused no damage to the divers' acoustic system, and the functions of their Eustachain tubes, middle and inner ears were normal during the diving test. PMID- 7882735 TI - [The classification of angina pectoris]. PMID- 7882737 TI - [Healing quality and recurrence of ulcer diseases]. PMID- 7882738 TI - [Analysis of risk factors in postinfarction angina]. AB - The clinical and echocardiographic variables related to postinfarction angina were evaluated in 54 patients with acute myocardial infarction. All patients underwent 2D echocardiography at 2-3 weeks after infarction. Wall motion analysis was quantified with a wall motion score index (WMSI) based on 16 left ventricular wall segments. Among the 54 patients with acute myocardial infarction 23 (42.6%) had early postinfarction angina. Multiple regression analysis demonstrated no significant difference between the patients with and without postinfarction angina in age, sex, location of infarction, Killip classification, previous angina, hypertension, hyperlipidemia, diabetes mellitus, creatine kinase level and left ventricular ejection fraction. In comparison with patients without postinfarction angina, patients with postinfarction angina had higher WMSI. It indicates that postinfarction angina appears to be related more to myocardial ischemia rather than to the infarct of myocardium. PMID- 7882739 TI - [Clinical features and prognosis of paroxysmal atrial fibrillation in the elderly]. AB - Eighty one elderly patients with paroxysmal atrial fibrillation were studied with respect to clinical features, effect of antiarrhythmic drugs and prognosis. 35 (43.2%) patients were associated with coronary artery disease and/or hypertension, while 23 (28.4%) patients had no other cardiovascular diseases. The latter condition was significantly less in patients over 60 years old when they had the first paroxysmal attack. Atrial fibrillation became permanent in 18 (22.2%) patients. Left atrial enlargement and abnormal cardiac function were significant independent factors affecting the type of atrial fibrillation. During an observation period of 12-84 months, the incidence of cerebral embolism and cardiac death were 6.1% and 4.9% respectively in all cases. We did not find that the prognosis of patients was affected by the types of atrial fibrillation. PMID- 7882740 TI - [Primary pericardial mesothelioma: a clinicopathological analysis of 7 cases]. AB - Primary pericardial mesotheliona is a clinical rarity. 7 cases were reported in this paper. There were no typical clinical symptoms and signs. It could not be diagnosed simply with chest film, ECG or echocardiagram and was usually misdiagnosed as constritive pericarditis, tuberculous pericarditis etc. In order to make correct diagnosis, some investigative diagnose methods such as pathological examination of pericardial fluid and pericardial biopsy, Gallium-67 scintigraphy, Ber-EP4 antibody and immunohistochemical procedures should be employed. PMID- 7882741 TI - [Short-term energy and protein support in mechanically ventilated patients with acute exacerbation of cor pulmonale]. AB - Twenty-one mechanically ventilated patients with acute exacerbation of cor pulmonale had received home made "Nutritient" via nasal gastric tube as energy and protein support for four weeks (energy supplement 37-45 kcal.kg-1.d-1, protein 1.40-1.67 g.kg-1.d-1). Anthropometry, serum albumin, serum prealbumin were measured on the 1st day and at the end of the 1st, 2nd, 4th week of ventilation. The results were compared with those in 15 age-matched ventilated patients who received routine hospital nasal gastric feeding (energy 24-29 kcal.kg-1.d-1, protein: 0.92-1.09 g.kg-1.d-1). All patients were in protein deficient type malnutrition. At the end of the 1st week of ventilation, serum albumin dropped significantly in both groups, resulting in a status of mixed type malnutrition. At the end of the 2nd week, however, serum prealbumin in the experimental group (24.31 +/- 4.80 mg/dl) returned nearly to normal level, being significantly higher than that in the control group (15.10 +/- 3.10 mg/dl, P < 0.01). At the end of the 4th week, both serum albumin (3.90 +/- 0.31 g/dl) and prealbumin (27.33 +/- 3.30 mg/dl) in experimental group returned to normal, being also significantly higher than those in the control group (3.00 +/- 0.23 g/dl, P < 0.05; 17.11 +/- 3.22 mg/dl, P < 0.01). Anthropometry showed no significant change between the two groups during ventilation. It is shown that nasal tube administration of "Nutritient" provides much higher energy and protein as compared with routine nasal feeding, and enables the patient to overcome protein deficiency and to reach positive nitrogen balance earlier. PMID- 7882742 TI - [Antitumor activity of monoclonal antibody MI2 against immunosuppressive acidic protein in vitro]. AB - In vitro antitumor activity of monoclonal antibody MI2 that was made by our laboratory to direct against immunosuppressive acidic protein (IAP) was observed with MTT assay for cytotoxicity. The results showed that the growth of human gastric cancer cell line SGC 7901 was inhibited significantly (P < 0.01) when MI2 was added at a concentration of 7.81 mg/L or higher. The inhibition activity of MI2 appeared to be dose dependent. Increased cytotoxicity (up to 206.3%) of LAK cells against SGC7901 could be remarkably (P < 0.01) induced by addition of MI2 at a concentration of 1.95 mg/L, so the ratio of effector to target was 10:1. The enhancing effect of MI2 on LAK cell activity was also dose dependent. The antitumor activity of MI2 was not associated with human complements. PMID- 7882743 TI - [Churg-Strauss vasculitis]. AB - The author reported a clinical study of 8 cases of Churg-Strauss vasculitis which is a rare disease of unknown cause. The clinical features include allergic rhinitis (69%), sinusitis (88%), asthma (98%-100%), mononeuropathy (66%-98%), pulmonary infiltration and peripheral blood eosinophilia. The histopathologic manifestations are characterized by eosinophilic infiltration, granulomatous lesion and necrotising vasculitis. The lesions mentioned above may not appear simultaneously, but they may exist in different combinations. Therefore, not all the manifestations may be seen in a single biopsy specimen. According to the diagnostic criteria recommended by American College of Rheumatology Subcommittee on Classification of Vasculitis in 1990, 6 cases of this series can be diagnosed. The remaining 2 cases were confirmed by pathologic examination. This kind of vasculitis responds to steroid treatment with satisfactory results. PMID- 7882744 TI - [The detection and significance of HBV-DNA in serum and liver of advanced schistosomiasis patients]. AB - Hepatitis B virus deoxyribonucleic acid (HBV-DNA) and surface antigen (HBsAg) in the serum and liver specimens from 31 patients with advanced schistosomiasis were investigated. The patients have been followed up for six years. The presence of HBsAg and HBcAb in serum among patients with advanced schistosomiasis were significantly more frequent than that in the control group (P < 0.05), but the prevalence of HBV-DNA and HBeAg in the patients were not significantly different from that in the controls (P > 0.05). The positive rate of HBV-DNA and HBsAg in liver was 19.4% and 48.4% respectively, which were greater than that in serum. The presence of HBV-DNA in patients with advanced schistosomiasis was associated with high mortality and the cause of death was either hepatic failure or hepatocellular carcinoma. The results suggest that it is important to detect HBV DNA both in surum and liver. Antiviral therapy for patients with advanced schistosomiasis who had detectable HBV-DNA may improve the prognosis. PMID- 7882745 TI - [Atropine dependence during treatment of acute organophosphorus pesticides poisoning]. AB - In treating patients with acute organophosphorus pesticides poisoning, clinicians pay more attention to poisoning counterattack, while atropine dependence, which resembles counterattack, is not yet fully recognized. The authors analysed 1,039 patients with this kind of poisoning treated in 7 years. Among these cases 157 were dependent on atropine, consisting of 15.1% of the total. The clinical manifestations of the dependence were described. The diagnostic criteria of the dependence and its differential points from counterattack were suggested. It was found that higher occurrence rate of the dependence was seen in patients of younger age, with more severe poisoning and with longer duration and higher total dose of atropine treatment (P < 0.005 respectively). It is considered that its mechanism might be related to increased number of M-receptor and excessive accumulation of acetylcholine. It is suggested that quantitative analysis of relevant receptor be developed. PMID- 7882746 TI - [Unstable angina]. PMID- 7882747 TI - [The progress in the treatment of acute myeloid leukemia in the elderly]. PMID- 7882748 TI - Higher-order processing in the visual system. Introduction. PMID- 7882749 TI - Computational analysis of early visual mechanisms. AB - An important class of mechanism, image filtering, is normally used to model the first stages in the human visual process. A formal examination of the general computational properties of image filtering, looking at the logic of what image filtering should accomplish and how filtered images can be described, shows that image filtering does not make any useful information explicit. To do this, a further stage of post-filtering processing, termed image description, is necessary. With these image descriptions it is possible to establish relationships between the structures that emerge and the filters used. Three properties emerge that are of benefit: the structures are simply shaped when filters are used that are modestly orientation tuned; the responses are suitably primitive; and the response structures show spatial clusterings that can be used to identify certain classes of object. Within this framework, the properties of a range of oriented filters were examined in a series of computational experiments. Given a particular form of image description, the optimal filters in terms of response structure simplicity, primitiveness and flexibility show a degree of orientation selectivity corresponding to that obtained in mammalian vision. PMID- 7882750 TI - Physiology, morphology and spatial densities of identified ganglion cell types in primate retina. AB - The use of in vitro preparations of primate retina provides new perspectives on the mosaic organization and physiological properties of three ganglion cell types that project to the lateral geniculate nucleus: the parasol, midget and small bistratified cells. Dendritic field sizes and coverage for the three types suggest that their relative densities vary with eccentricity. Of the total ganglion cells in the human fovea, midget cells constitute about 90%, parasol cells about 5%, and small bistratified cells about 1%. In the periphery, midget cells make up about 40-45%, parasol cells about 20% and small bistratified cells about 10% of the total. Thus from peripheral to central retina the number of midget ganglion cells progressively increases relative to the parasol and small bistratified types. Physiological properties of these cells have recently been studied in macaque (Macaca nemestrina) retina by combining intracellular recording and dye injection. As expected, parasol cells, projecting to geniculate magnocellular layers, give phasic, non-opponent light responses. Midget cells, which project to geniculate parvocellular layers, show opponent responses sensitive to only mid and long wavelengths; no evidence of short-wavelength sensitive cone (S-cone) input to any midget ganglion cell has been found. However, the small bistratified cells, which also project to the parvocellular geniculate layers, give a strong blue-ON response to stimuli designed to modulate S-cones. Thus, S-cone and medium- or long-wavelength-sensitive cone opponent signals arise from morphologically distinct ganglion cell types that project in parallel to the lateral geniculate nucleus. PMID- 7882751 TI - The role of features in structuring visual images. AB - Edges and lines carry much information about images and many models have been developed to explain how the human visual system may process them. One recent approach is the local energy model of Morrone and Burr. This model detects and locates both lines and edges simultaneously, by taking the Pythagorean sum of the output of pairs of matched filters (even- and odd-symmetric operators) to produce the all-positive local energy function. Maxima of this function signal the presence of all image features that are then classified as lines or edges (or both) and as positive or negative, depending on the strength of response of the even- and odd-symmetric operators. If the feature is an edge, it carries with it a brightness description that extends over space to the next edge. The model successfully explains many visual illusions, such as the Craik-O'Brien, Mach bands and a modified version of the Chevreul. Features can structure the visual image, often creating appearances quite contrary to the physical luminance distributions. In some examples the features dictate totally the image structure, 'capturing' all other information; in others the features are seen in transparence together with an alternate image. All cases can be predicted from the rules for combination of local energy at different scales. PMID- 7882752 TI - From filters to features: location, orientation, contrast and blur. AB - Consider three main ideas about spatial filtering and feature coding in human spatial vision. (1) Computational theory: the representation of local luminance features--bars and edges--is a crucial step in human vision, forming the basis for many decisions in pattern discrimination. (2) Algorithm: features may be located and characterized in terms of polarity, blur and contrast by comparison of 1st, 2nd and 3rd spatial derivatives taken at a common point. Edges in compound (f + 3f) gratings are seen at or close to peaks of gradient magnitude. More tentatively, bars may be located at peaks of the 2nd derivative or at peaks in the Hilbert transform of the 1st derivative. Peaks of contrast energy do not predict all the features seen. An algorithm for recovering the blur of edges is derived as the square-root of the ratio of 1st to 3rd derivatives at the edge location. This successfully predicts blur matching between Gaussian edges and a variety of other test waveforms, including sine waves. Blur matching is (nearly) contrast invariant, as predicted by this ratio rule. (3) IMPLEMENTATION: experiments on the perception and discrimination of plaids imply that the outputs of tuned filters are combined before feature coding. The adaptive, weighted summation of bandpass filters may serve to synthesize the derivative operators while facilitating the segmentation of overlapping features and preventing the representation from being swamped by noise. PMID- 7882753 TI - Collator units: second-stage orientational filters. AB - Which parts of an image belong to the other parts? This has become known as the 'binding problem' and is almost as resistant to explanation now as it was over half a century ago, when the purely descriptive Gestalt rule of 'good continuation' and the like were formulated. The specific case of interest here is that of spatially sampled fragments of a continuous but partly occluded line. First-stage orientated visual filters with relatively small receptive fields (such as simple cells) make precise but essentially local measurements of the orientational properties of line fragments within their spatial domain. I suggest that these units act as 'tributary units', their outputs becoming the inputs to 'collator units', which are second-stage oriented filters whose function is to put together the local descriptions of the spatially distributed line fragments. The functional receptive field of the collator units would be the spatial sum of the receptive fields of the tributary units. If the tributary units all have the same orientation preference and their fields are axially aligned end to end, the receptive field of the corresponding collator unit would have the same orientation preference and width as its tributary units, but would be considerably longer. Psychophysical data are presented which are consistent with this model. PMID- 7882754 TI - Non-Fourier motion analysis. AB - It has been realized for some time that the visual system performs at least two general sorts of motion processing. First-order motion processing applies some variant of standard motion analysis (i.e. spatiotemporal Fourier energy analysis) directly to stimulus luminance, whereas second-order motion processing applies standard motion analysis to one or another grossly non-linear transformation of stimulus luminance. We have developed a method for disentangling the different sorts of mechanisms that may operate in human vision to detect second-order motion. This method hinges on an empirical condition called transition invariance that may or may not be satisfied by a family psi of textures. Any failure of this condition indicates that more than one mechanism is involved in detecting the motion of stimuli composed of the textures in psi. We have shown that the family of sinusoidal gratings oriented orthogonally to the direction of motion and varying in contrast and spatial frequency is transition invariant. We modelled the results in terms of a single-channel motion computation. We have new results indicating that a specific class of textures differing in texture element density and texture element contrast decisively fails the test of transition invariance. These findings suggest that in addition to the single second-order motion channel required by our earlier results there exists at least one other second-order motion channel. We argue that the preprocessing transformation used by this channel is a pointwise non-linearity that maps stimulus contrasts of absolute value less than some relatively high threshold tau onto 0, but increases with magnitude of c-tau for contrasts. c of absolute value greater than tau. PMID- 7882755 TI - Implications of motion detection for early non-linearities. AB - Analysis of motion may be accomplished using the spatiotemporal variations produced when a spatially varying luminance waveform moves across linear receptive fields. Moving contrast-modulated patterns which consist of coarse scale spatial variations in the contrast of fine-scale luminance patterns cannot be analysed in this way. The human visual system can analyse the motion of contrast-modulated patterns and this suggests it may contain mechanisms that use non-linear transformations. Non-linear transformation of contrast-modulated patterns would give rise to a component (a distortion product) that varies on the same spatial scale as the contrast variation; this can be analysed to extract motion. Is the non-linearity simply an inherent part of the transduction process or is it a characteristic of a mechanism specialized for the analysis of the motion of such patterns? Comparisons of the spatial and temporal limitations of motion discrimination using luminance and contrast-modulated patterns suggest that the mechanisms which analyse the two types of patterns are different, although recent physiological evidence suggests that they may have common elements. PMID- 7882756 TI - The role of second-order motion signals in coherence and transparency. AB - Second-order or non-Fourier motion was originally demonstrated in the laboratory by the use of contrast-modulated stimuli of various types. As these stimuli seem somewhat artificial, it might be questioned whether they play a significant role in the processing of natural motion. An affirmative answer is provided by the key observation that the non-Fourier motion apparatus analyses the motion of texture boundaries in two-dimensional patterns. Given this, a wide range of motion phenomena can be explained by a neural model that combines both Fourier and non Fourier motion signals in a neural network that computes the vector sum direction. The existence of a vector sum computation is supported by two observations: patterns composed of two cosine gratings ('plaids') appear to move in the vector sum direction during brief presentations and plaids composed solely of non-Fourier components always move in the vector sum direction. The neural model predicts these results and also agrees with much of area MT physiology. Within this context, many instances of motion transparency result when the angle between Fourier motion directions is large (> 90 degrees) and the non-Fourier motion signal is minimal or absent. PMID- 7882757 TI - Common properties of visual segmentation. AB - Recent experiments on the psychophysics of texture segmentation have produced several interesting observations that provide a useful basis for discussing the underlying neuronal mechanisms. Segmentation is predominantly achieved by analysis of local differences across a texture border, not global similarities. This suggests the involvement of a local, orientation contrast-sensitive mechanism similar to lateral inhibition in the retina. For segmentation to occur, orientation differences at the texture border must be increased when the overall orientation variation in the background of a pattern is raised. Similar properties are found for other visual clues that provide perceptual segregation. For motion, segmentation is based on the detection of local differences between areas rather than the analysis of global motion coherence within areas. Such local differences must be increased for successful segmentation when background movement is made non-uniform. Colour, luminance and binocular disparity behave in a similar way, suggesting a general role for feature contrast in visual segmentation. PMID- 7882758 TI - A computational model for shape from texture. AB - Shape from texture is best analysed in a two-stage framework analogous to stereopsis and structure from motion: (a) computing the 'texture distortion' from the image; and (b) interpreting the 'texture distortion' to infer the orientation and shape of the scene surface in 3D. We model the texture distortion at a point in any particular direction on the image plane as an affine transformation and derive the relationship between the parameters of the affine transformation and the surface shape and orientation. We have developed a technique for estimating affine transforms between nearby image patches which is based on solving a system of linear constraints derived from a differential analysis. It is not necessary explicitly to identify texels or make restrictive assumptions about the nature of the image texture like isotropy. We have developed two different models for recovering surface orientation (slant and tilt) and shape (principal curvatures and directions) based on the estimated affine transforms in a number of directions. Experimental results are presented on images of planar and curved surfaces under perspective projection. PMID- 7882759 TI - Full-wave and half-wave processes in second-order motion and texture. AB - A theory of human second-order motion perception is proposed and further applied to the discrimination of texture slant. The computational algorithms for deriving the direction of left-right motion from a sequence of images are equivalent to the algorithms for deriving the direction of slant (e.g. from top left to bottom right or top right to bottom left) in a single 2D image. There is a broad range of phenomena for which Fourier analysis of the image plus a few simple rules gives a good account of human perception. The problem with this first-order analysis is that there exists a broad class of 'microbalanced' stimuli in which the motion or slant is completely obvious to human subjects but is invisible to first-order analysis. Microbalanced stimuli require second-order analysis which consists of non-linear preprocessing (spatiotemporal filtering followed by rectification of the input signal) before standard motion or slant analysis. To determine whether the second-order rectification is half-wave or full-wave, we construct two special microbalanced stimulus types: 'half-wave stimuli' whose motion (or texture slant) is interpretable by a half-wave rectifying system but not by full-wave or a first-order (Fourier) analysis and 'full-wave stimuli' which are interpretable only after full-wave rectification. Such experiments show that second-order texture-slant perception utilizes both half-wave and full-wave processes, second-order motion-direction discrimination depends predominantly on full-wave rectification and second-order spatial interactions such as lateral contrast-contrast inhibition and second-order Mach bands are exclusively full wave. PMID- 7882760 TI - Non-linearities in texture segregation. AB - The existence of complex (non-Fourier, second-order) channels is suggested by some characteristics of segregation perceived between regions distinguished by visual texture. These complex channels consist of two linear-filtering stages separated by a rectification-type non-linearity. We have investigated (i) the spatial frequency selectivity and orientation selectivity of their first-stage filters; (ii) the relationship between the preferred values of orientation and spatial frequency at the first and second filters; (iii) spatial pooling and its implications for the non-linearity at the middle of the complex channel; and (iv) the dynamics of complex and simple linear channels. An intensive non-linearity is also necessary to explain perceived region segregation. This intensive non linearity might arise from an early local non-linearity preceding the channels (perhaps retinal light adaptation) or from normalization among the channels themselves (perhaps due to intracortical inhibition). Deciding between these two candidates has been more difficult than we had hoped. It appears that: (i) this intensive non-linearity operates for both simple and complex channels; (ii) the effects on it of changing mean luminance or spatial scale may be accounted for by a sensitivity parameter; (iii) it can be dramatically compressive even at contrasts less than 25% for high mean luminances and large scales; and (iv) at even lower contrasts there is an accelerating non-linearity that acts before the second filter of the complex channels. PMID- 7882762 TI - Linearity and non-linearity in cortical receptive fields. AB - Visual neurons in striate (V1) cortex have been studied as feature detectors or as spatiotemporal filters. A useful way to distinguish between these two conceptual approaches is by studying the way in which visual signals are pooled across space and time. Many neurons in layer IV of striate cortex exhibit linear spatial summation and their response time course is consistent with linear temporal summation. Neurons in supragranular and infragranular layers sum signals in a non-linear manner. A particularly important non-linearity seen in many cortical complex cells is non-linear summation along an axis parallel to their preferred orientation. This leads to responsiveness to 'illusory contours', borders defined by texture differences only. These and other results on non linear summation of chromatic and achromatic signals imply that V1 cortex performs sophisticated and complex image processing and is not simply an array of spatiotemporal filters. PMID- 7882763 TI - Non-linear dynamics of columns of cat visual cortex revealed by simulation and experiment. AB - Correlation images were derived from simultaneous recordings of 12 signals representing the synaptic activity at different layers of a column in cat visual cortex (area 18) and 12 signals representing the local average spiking activity at the same locations. Because the ongoing activity and the activity evoked by stroboscopic flashes yielded the same correlation image, ongoing activity is caused by an input to a column similar to flash-evoked activity and is thus not endogenous. Moving bar stimuli evoked bursts of oscillations (25-75 Hz band) in the correlation image. The rhythm of these oscillations was not related to any frequency component in the stimulus. In all correlation images we observed that synaptic activity in one layer resulted in simultaneous spiking activity in all layers with latency differences smaller than 2 ms (the sample interval used). Similar behaviour was observed in a simulation experiment where we 'realistically' modelled one column of visual cortex with 1000 three compartmental neurons in 11 functional layers. When such a model column was tuned to yield a stable and excitable system with low ongoing activity, activation of any of the layers caused simultaneous activity in all 11 layers. Both the simulation and the experimental results suggest that a column can be regarded as a basic processing element sending the same information over all its outputs to other columns within the same cortical region, other visual areas and subcortical structures. PMID- 7882761 TI - Circuitry, architecture and functional dynamics of visual cortex. AB - A fundamental understanding of the mechanisms of cortical processing requires an examination of the relationships of cortical circuitry, cortical functional architecture and receptive field properties. Ultimately, this kind of analysis can be used to explore the neurobiological basis of psychophysics and perception. At the outset our studies were intended to account for the then known receptive field properties of cortical cells in terms of their underlying circuitry but, surprisingly, a good part of the cortical circuit appeared to be in violation of the principles of cortical architecture. This led us to explore the possibility of new, more complex properties of cortical cells. It has become increasingly possible to relate the responsive specificity of cortical cells and the circuitry underlying this specificity to the perceptual capabilities of the visual system by performing analogous experiments on single cells and in human psychophysics. PMID- 7882764 TI - [Adult spondylolisthesis treated with the combination of angled and pushing pulling pedicle screws]. AB - Altogether 28 patients with degenerative (22 cases), isthmic (4 cases), and post traumatic (2 cases) spondylolisthesis were treated with a reduction fixation system using both angled and pushing-pulling pedicle screws. Preoperatively, the percentages of the sliprage were < or = 25% in 15 cases, < or = 50% in 11, and < or = 75% in 2 cases. All patients had low-back pain and/or leg pain. Postoperatively, 28 cases obtained a nearly anatomical reduction. The average rate of correction was 98%. There is a significant difference (P < 0.01) compared with preoperation. After reduction, all patients had only two segmental rigid fixations with posterolateral bone grafting or postero-inter-body fusion. 27 cases had satisfactory pain relief postoperatively. No patient deteriorated neurologically with surgery. All patients were followed up for a minimum of 8 months ranging from 8 to 28 months (average 19). At the end of follow-up, in 26 patients correction remained unchanged with X-ray demonstrating radiographic evidence of fusion. Neither pseudarthroses nor significant complications occurred. The new system is a safe and effective pedicular fixation system, it has a three-dimensional correction force that allows for reduction of the spondilolisthesis and fixation of only two segments. It also gives more rigid fixation to maintain the reduction and increase the fusion rate. The new system gives satisfactory results over conventional hook and sub-lamina wire and other segmental spinal pedicle screw instrumentation systems. PMID- 7882765 TI - [Treatment of lumbar spinal stenosis with partial laminectomy and canal enlargement]. AB - Thirty-eight patients with lumbar spinal stenosis were treated by partial laminectomy, incision of ligmental flava and canal enlargement. According to the pathological characteristic of lumbar spinal stenosis, both decompression and stability of the lumbar spine would be achieved by limited surgical treatment to the pathological segment and removing of any pathological factors. The average time for follow-up is 14 months. The excellent rate is 89.5%. The technique of the operation was also described and discussed. PMID- 7882767 TI - [Protrusion of thoracic intervertebral disk: report of 11 cases]. AB - The authors reported 11 cases of thoracic intervertebral disk protrusion examined with plane film, myelography, CT and CT-myelography in 11 cases and MR imaging in 3. All of the 11, cases were confirmed by operation. There were 13 protrusions in the 11 cases with the locations of T10-11 in 4, T11-12 in 5 cases and T12-L1 in 4. 9 protrusions fell into central type, 1 into paracentral type and 1 into lateral type. The clinical symptoms were prominent with all 11 cases, however, most primary clinical diagnoses were erroneously given as lumber intervertebral disk protrusions and even the disorders of heart, lung, alimentary tract and urinary system. It was concluded that the main causes of the misdiagnosis included: (1) not easily to think of this entity for the clinic physicians due to its low incidence, (2) the untypical clinical manifestations. The authors considered that the exam method with the highest accuracy is CT-myelography. PMID- 7882766 TI - [Classification and surgical treatment of lumbosacral nerve root anomalies]. AB - In this paper 12 cases of lumbosacral nerve-root anomalies proved on operations were reported. Two roots with a common conjoined origin entering the common intervertebral foramen separately were seen in two cases; two roots arising respectively from the lateral and ventral sides of the dural sac at the level of upper margin of the pedicle, in which one ran transversely into the foramen and another obliquely ran downward, in one case; two roots with closely adjacent origins, in which one ran transversely into the foramen at the level of upper margin of the pedicle and another obliquely ran downward, in four cases; a single root with abnormally large whereas the adjacent root with abnormally small, in five cases. We proposed a classification method for the sake of appropriate surgical program, which assorted the anomalies into three types: (I) General volume of nerve roots in the spinal canal or nerve-root canal abnormally increased, either the diameter of a single root increases or two roots entered the common. foramen; (II) The origin and course of two roots were anomalous; (III) Combination of I and II. PMID- 7882768 TI - [The measurement of collagen and proteoglycan contents in nucleus pulposus of lumbar intervertebral disc]. AB - The collagen and proteoglycan contents were determined in lumbar intervertebral disc nucleus from 50 cases normal Chinese with accidental death and in that of 50 cases of prolapsed lumbar intervertebral disc (PID). The significance of the work rested with. (1) The normal range of the collagen and proteoglycan contents in the nucleus pulposus of normal Chinese was defined, therefore, it provided a normal parameter and laid a foundation for the study of collagen and proteoglycan metabolic changes in the nucleus pulposus of lumbar intervertebral disc under pathological condition. (2) By comparison of contents between collagen and proteoglycan in the nucleus pulposus of PID, the physiopathology of PID was confirmed further, that is, the content of proteoglycan of the nucleus pulposus in PID decreased, however, that of collagen increased. (3) The collagen contents between fibrocartilage and nucleus pulposus in normal chinese were compared. Analyses were made biomechanically and biochemically. PMID- 7882769 TI - [Manufacture and usage of a new rotatometer of spine]. AB - The purposes of this research are to study the changes of some projective points of vertebrae on roentgenogram during consecutive axial rotation and to design and manufacture a new rotatometer of spine for clinical and research work. Using 2 anatomic specimens of normal spines, aged 10 and 17 years. We took anteroposterior roentgenograms for each vertebra during consecutive axial rotation from 0 th 90 degrees. Some projective points on the roentgenograms were selected. Changes of the projective points were measured. The data were analysed with the stepwise regression, linear fitting in a microcomputer. The rotatometer was designed and manufactured upon the linear regressional equation. The results showed that there was an excellent correlation between actual rotation of vertebra and changes of the projective points on anteroposterior roentgenograms. The distances between the center of vertebral pedicle and lateral edge on convex side of vertebra and rotation angle Q were the reliable references which express the actual axial rotation of vertebra. We thought that rotation angle Q was the mark which had advantages of definition, directness, precision and extended measurable range. The 3 sets of graduations were used to measure the segments of T3-6, T7-12 and L1-4 neuromuscular scoliosis, some congenital scoliosis and axial rotation of spine without certain causes in adolescents. Quantitative measurement of scoliotic rotation is very important for determinating and selecting schemes of operations on scoliosis. It is also helpful to predict prognosis of scoliosis and evaluate the results of corrective operations on spinal deformity. PMID- 7882770 TI - [Preliminary report on portal hypertension treated by transjugular intrahepatic portosystemic stent shunt]. AB - Transjugular intrahepatic portosystemic stent shunt (TIPSS) was carried out in 50 cases of liver cirrhosis with portal hypertension. An average Child-Pugh score in these cases was 10.33 +/- 2.34. Except for 5 cases with portal vein occlusion, the technical success rate of in 45 cases was 95.6%. Acute variceal bleeding was immediately controlled. Portal pressure was reduced by 1.36 +/- 0.48 kPa. Esophageal varices and ascites disappeared. The shrink of spleen, the reducing of body weight were also observed in a week following TIPSS. The velocity of blood flow in stents was 85.61 +/- 35.83 cm/s. Follow-up of 1-9 months found norebleeding and ascites. The velocity of blood flow in stents was 83.83 +/- 34.74 cm/s. Three patients died of liver failure and variceal rebleeding within a month after TIPSS. Slight encephalopathy was observed in 6 cases. PMID- 7882771 TI - [Combined color Doppler and pulsed Doppler in the diagnosis of small hepatocellular carcinomas]. AB - The combined studies by using color Doppler (CD) and pulsed Doppler (PD) technique in 56 patients with 71 solid hepatic lesions smaller than 3 cm in diameter were carried out. The detecting rates of arterial signals in small hepatocellular carcinomas (sHCC) group, hepatic cavernous hemangiomas (HCH) group and others group were 86.9%, 37% and 33% respectively. Whereas, the average value of resistance index (RI) in sHCC group was very higher than that in other groups. By using combined CD and PD space-taking lesions of the liver are tentatively diagnosed as sHCC under conditions of color flow, arterial signals, and a RI of more than 50%. The specificity (96%) and accuracy (90%) of the diagnosis superior to the conventional US (P < 0.005). PMID- 7882772 TI - [Nonoperative treatment for simple hepatic injury: an analysis of 77 cases]. AB - In this study, 77 of 82 hepatic injury cases were selected for conservative therapy. The hepatic injuries in all these 77 cases were originally graded as type I or Type II by reviewing the history of trauma, abdominal paracentesis, B mode ultrasonography, peritoneoscopy, X-ray pneumoperitoneography, and serum GPT measurement. Patients were all resuscitated by fast volume expansion, blood transfusion recovered from intraabdominal bleeding, nasogastric tube decompression added by chinese herbs. Three patients died of compound internal organ injuries, respiratory failure and DIC, the remaining 74 (96.1%) were cured. PMID- 7882773 TI - [p21ras expression, DNA ploidy and prognosis in colorectal cancer]. AB - 83 colorectal cancer patients who underwent radical surgery were studied. Serial sections were carried out for detection of p21ras expression level by means of immunohistochemical assay combined with image analysis technique, measurement of DNA ploidy by flow cytometry and re-confirmation of diagnosis. We found that the high level of p21ras expression indicated a group of tumors with more aggressive behavior and worse prognosis. The five-year survival rate was only 26.83% in patients with p21D > or = 0.24 tumor, compared with 78.57% in those with p21D < 0.24 tumor. Five-year survivors tended to display diploid and had lower p21D. Detection of p21ras expression level (p21D) and DNA index in tumors may be helpful in predicting the outcome of colorectal cancer patients. PMID- 7882774 TI - [Flow cytometric quantitation of p53 protein expression in gastrointestinal smooth muscle tumors: clinicopathological correlation and prognostic significance]. AB - Quantitative analysis of p53 protein expression was performed on paraffin embedded tissues from 55 smooth muscle tumors of the gastrointestinal tract by using immunofluorescence and flow cytometry. No positive expression was found in normal smooth muscle tissues of the gastrointestinal tract. Overexpression of p53 gene was found in a significantly higher proportion in leiomyosarcomas (90%) and potential malignant smooth muscle tumors (75%) compared to leiomyomas (14%) (P < 0.005). The quantitation of p53 expression was found to be progressively enhanced in the sequence from leiomyoma through potential malignant smooth muscle tumor to leiomyosarcoma (P < 0.005). It was also overexpressed when mitotic counts were more than 1/10HPF or the mild cytologic atypia was found (P < 0.005). Five year survival rate was significantly higher in the patients with p53 lower expression compared to the patients with over-expression (P < 0.005). These results suggested that p53 overexpression might be associated with the transformation of leiomyoma into leiomyosarcoma, and could be used as an objective parameter in distinguishing malignants from benigns and predicting prognosis of the patients with smooth muscle tumors of the gastrointestinal tract. PMID- 7882775 TI - [Abnormalities of anti-oncogene p53 in renal cell carcinoma]. AB - Mutant forms of p53 gene are found in numerous human malignancies. Studies of the p53 mRNA showed different levels of expression in many tumours. But the relationship between the p53 gene and the renal cell carcinoma is less elucidated than the other. In this report we examined p53 gene at mRNA level by Northern blot on the tissues from 21 patients with renal cell carcinoma. Abnormalities of the p53 were found in 12(57%) tumors, in which seven had elevated level of p53 mRNA, and five lacked p53 mRNA. p53 gene alteration occurred in a high percentage in high-grade and advanced tumors. These results suggest that inactivation of p53 gene is common in renal cell carcinoma and may be involved in the progression of this malignancy. PMID- 7882776 TI - [Epidermoid cysts of testicle: a report of 4 cases]. AB - Epidermoid cysts of testicle is a kind of rare benign tumors of testicle, about 1% of all testicle tumors. In this paper, we described 4 cases of epidermoid cysts of testicle. Based on clinical manifestations, features of B-ultrasound, and other information, epidermoid cysts's histogenesis, pathology and classification were discussed. B-ultrasound is a powerful technique to derive a definite diagnosis before operation. Patients can be cured only by orchiectomy, and much attention should be paid to possible canceration. PMID- 7882777 TI - [Percutaneous catheter drainage for post-traumatic perinephric urinoma]. AB - From June 1989 to April 1992, 5 patients with post-traumatic perinephric urinoma were treated by using percutaneous catheter drainage. The urinoma disappeared and the renal function restored in all the 5 patients 18-27 days (average 21.8 days) after continual drainage. Follow-up for 1-4 (averaging 2-6 years) years showed non-recurrence of the urinoma in all the 5 patients. The procedure is characterized by less distress and economical to the patients. It can keep the kidneys intact. The pathogenesis, pathology, diagnosis and treatment are discussed along with a review of the literature. PMID- 7882778 TI - [Stereotactic radiosurgery by isocentric linear accelerator]. AB - Stereotactic radiosurgery by isocentric linear accelerator, new technique developed in neurosurgery, was used to treat 92 patients with deeply localized cerebral tumors. Its indications and the techniques of improving its effect, preventing its complication were underlined. PMID- 7882779 TI - [Clinic analyses of digestive tract bleeding due to hypertension and intracerebral hematomas]. AB - This paper reports 14 cases with digestive tract bleeding due to hypertension, and intracerebral hematomas, among which five cases suffer from severe bleeding. The paper analyses its clinical manifestations, mechanism and treatment. The author believes that digestive tract bleeding easily occurs with consciouslessness, great quantity of intracerebral hematomas into ventricles and injury of brain stem. The bleeding moment may occur in acute period or in recovery period. It will reach a good result to treat comprehensively. PMID- 7882780 TI - [Myocardium protection using warm blood cardioplegia in corrective operation of tetralogy Fallot]. AB - In this paper, the children, who had undergone the operation with the approach similar to that of Tetralogy Fallot, were selected and divided into 4 groups, according to different kinds of cardioplegia were infused during corrective operation. St. Thomas group (CC group) 24 cases, cold blood cardioplegia group (CBC group) 21 cases, terminal warm blood cardioplegia group (TWBC group) 12 cases, and continuous warm blood cardioplegia group (CWBC group) 12 cases. Through the measurement of left ventricular contraction pressure and CK-Mb release in the postoperative period, the effect of myocardial preservation was better in TWBC and CWBC groups than in CC and CBC groups (P < 0.05), ATP volume of myocardium in TWBC and CWBC groups were higher (17.1 and 18.2 mumol/g) than that in CBC group (2.48 mumol/g) (P < 0.01) CP values were respectively 8.74 mumol/g, 7.63 mumol/g and 5.5 mumol/g (P < 0.05). 9 cases (37%) in CC group needed inotropic drug to assist circulation postoperation, 4 cases (16%) in CBC group, 2 cases (12%) in both TWBC and CWBC group. The results demonstrated that WBC had a better myocardial protection effect. PMID- 7882781 TI - [The surgical treatment of partial atrioventricular canal defect]. AB - This paper reports 11 cases of partial atrioventricular canal defect in our hospital. It also discusses the diagnosis of complication prevention and treatment with patient and the disposal during operation term, emphasizes that once definite diagnosis has been made, operation must be taken as soon as possible. Skillfully grasp surgery anatomy and exact suture techniques is the key to avoid conduction damage. PMID- 7882782 TI - [The etiological study of idiopathic scoliosis]. PMID- 7882783 TI - Rectal mucosectomy in the treatment of giant rectal villous tumors. AB - PURPOSE: Rectal mucosectomy, a technique adapted from restorative proctocolectomy, has been used to treat large rectal villous tumors. We compared morbidity, tumor control, and functional outcome following rectal mucosectomy with the results of more conventional transanal excision and piecemeal snaring and fulguration in patients with large rectal villous tumors. METHODS: We retrospectively reviewed the charts of inpatients who had undergone transanal surgery for villous tumors. RESULTS: Between 1983 and 1993, rectal mucosectomy, transanal excision, and snaring and fulguration were performed, respectively, in 12, 26, and 23 patients with large rectal villous tumors. Tumors treated by rectal mucosectomy had a larger mean diameter (8.5 cm) than those treated by transanal excision or snaring and fulguration (4.5 cm and 4.2 cm, respectively; P < 0.0001, analysis of variance). After a mean follow-up of 47 months, incidence of tumor persistence was 17 percent following rectal mucosectomy, 20 percent following transanal excision, and 40 percent following snaring and fulguration (P = 0.04, chi-squared). Tumor recurrence was 8 percent after rectal mucosectomy compared with 36 and 44 percent, respectively, after transanal excision (P = 0.09, chi-squared) and snaring and fulguration (P = 0.04, chi-squared). Clinically significant postoperative bleeding did not occur after rectal mucosectomy; 17 percent of patients had persistent mild incontinence. CONCLUSIONS: Rectal mucosectomy for villous tumors, a new application of an established technique, is safe and associated with low rates of tumor persistence and recurrence. Rectal mucosectomy may result in mild incontinence and should be reserved for large or circumferential lesions. For smaller lesions, transanal excision results are more reliable tumor eradication than snaring and fulguration. PMID- 7882784 TI - Unilateral anal electrosensation. Modified technique to improve quantification of anal sensory loss. AB - PURPOSE: Anal electrosensation is usually tested by an annular configured electrode that stimulates the circumference of the anus. In certain pelvic conditions, the right and left pudendal nerve function may be damaged separately and to different degrees. This may only be detected by a unilateral electrode testing each side independently. METHODS: Our study compares accuracy and sensitivity of annular and unilateral electrodes in assessing patients with hemorrhoids, perineal descent, incontinence, after low anterior resection, and constipation (107 subjects). RESULTS: In normal controls (n = 19), annular thresholds ranged from 0.5 to 2.7 mA and unilateral thresholds from 0.6 to 2.6 mA. In prolapsed hemorrhoids, unilateral was more sensitive than annular electrode in detecting deficits at the upper (P < 0.0001), mid (P < 0.005), and lower (P < 0.0005) anus. Patients with perineal descent had a sensory deficit in the upper anal canal, detected more consistently by unilateral electrode (P > 0.05). No significant abnormalities were found in neuropathic incontinence, after anterior resection and chronic constipation. Results of the unilateral electrosensory technique were found to be consistent with repeated measurements (r = 0.8878; P < 0.001). CONCLUSIONS: By being more sensitive than the annular technique, the unilateral electrode method may become, with refinement, a useful test for quantifying anal sensation. PMID- 7882785 TI - Patterns of colorectal liver metastases according to Couinaud's segments. AB - PURPOSE: It is commonly believed that the right lobe of the liver is the most frequent site of colorectal liver metastases. However, direct evidence for this is lacking in the literature. This study was designed to document and evaluate the pattern of liver metastases according to liver segments. METHODS: A retrospective medical records review of 270 patients with hepatic metastases from colorectal adenocarcinoma was performed to determine the pattern of metastases according to Couinaud's segments. There was operative confirmation of liver metastases in 202 patients (75 percent). A total of 1,166 segments were involved with liver metastases and were used in this analysis. Segment I was excluded from calculations because of its dual blood supply. When groups contained different numbers of Couinaud's segments an appropriate correction was made in the statistical comparison. RESULTS: There were 736 (63 percent) right lobe segments (V, VI, VII, VIII) and 430 (37 percent) left lobe segments (II, III, IV) involved with metastases (P < 0.001). Of 430 left lobe segments, 298 (69 percent) involved the left lateral segment (II, III) and 132 (31 percent) involved the medial segment (IV) of the left lobe (P = 0.25). When evaluating patients with 4 or less segments involved, there were 258 right lobe segments (75 percent) and 88 left lobe segments (25 percent) involved with metastases (P < 0.0001). Of 88 left lobe segments with 4 or less segments involved, there were 68 segments (77 percent) involving the left lateral segment and 20 segments (23 percent) involving the medial segment of the left lobe (P = 0.035). All of these relationships were statistically independent of the primary tumor site. CONCLUSIONS: We have documented an overall predominance of right hepatic lobe metastases independent of site of the primary colorectal carcinoma. However, when metastases occurred in the left lobe, the left lateral segment (II, III) was more commonly affected than the medial segment (IV), but this difference was statistically significant only when there were four or less segments involved with liver metastases. PMID- 7882786 TI - Unsuspected sphincter defects shown by anal endosonography after anorectal surgery. A prospective study. AB - PURPOSE: Anorectal surgery can lead to fecal soiling and incontinence. Whether surgery changes the anatomy and causes symptoms is unknown. Anatomic changes can be visualized by anal endosonography. METHODS: We studied 50 patients after hemorrhoidectomy (24), fistulectomy (18), and internal sphincterotomy (8). Symptoms were assessed, and anal endosonography, anal manometry, mucosal electrosensitivity, and neurophysiologic tests were performed. RESULTS: In 23 (46 percent) patients, a defect of the anal sphincter was found (13 patients had an internal sphincter defect, 1 had an external sphincter defect, and 9 had a combined sphincter defect), 3 after hemorrhoidectomy, 13 after fistulectomy, and 7 after internal sphincterotomy. Seven patients had symptoms, and they all had a sphincter defect. In the other 16 of 23 patients (70 percent), the sphincter defect did not produce symptoms. An internal sphincter defect lowered maximum basal pressure and shortened sphincter length. CONCLUSION: Anal endosonography can reveal sphincter defects after anorectal surgery. Seventy percent of the patients in this group had no complaints; therefore, defects were unsuspected. This has clinical implications in the evaluation of patients with fecal incontinence. PMID- 7882787 TI - Randomized trial of pelvic drainage after rectal resection. AB - Most surgeons continue to advocate routine use of drains after pelvic anastomoses. Several recent studies have, however, demonstrated that patients gain little or no benefit from such drainage and that drains may indeed be a source of morbidity to some. PURPOSE: The aim of this trial was twofold: 1) to determine whether use of a high pressure, closed suction pelvic drain was associated with reduced morbidity; 2) to investigate the influence of drainage on postoperative fluid collections after rectal resection. METHODS: A consecutive series of 100 patients was randomized to receive either no drain (n = 48) or a high pressure, closed suction intraperitoneal drain for seven days (n = 52). The two groups were similar in terms of age, sex, diagnosis, and type of anastomosis. Patients underwent postoperative pelvic ultrasound and water-soluble contrast studies on day 7. RESULTS: There were six deaths (three drain, three no drain). Clinically significant anastomotic leak occurred in seven patients (five drain, two no drain), and a radiologic leak was demonstrated in another five patients (two drain, three no drain), each of whom remained well. Presence or absence of a drain did not influence rate of morbidity and mortality. Pelvic fluid collections were more likely to be demonstrated if a drain was used; however, this did not reach statistical significance. Neither pus nor feces emerged from the drain in any patients in whom a leak occurred. CONCLUSION: Use of a pelvic drain after rectal resection did not confer any benefit to the patient. PMID- 7882788 TI - Why do some patients experience poor functional results after anterior resection of the rectum for carcinoma? AB - PURPOSE: The aim of this study was to examine the dynamic inter-relationship of the anal sphincter, residual rectum, and neorectum after low anterior resection for rectal carcinoma. METHODS: Seventy-three patients underwent laboratory tests of anorectal function a median of ten (range 1-100) months after operation. All patients completed quality of life questionnaires and had the level of their anastomoses determined by rigid sigmoidoscopy. Forty-four patients (60 percent) had some form of disturbance of bowel function, which was classified as "poor" function if bowel frequency was four or more in 24 hours and if there was also either fecal leakage or urgency of defecation. Manometric data were analyzed using stepwise logistic regression analysis. RESULTS: Only two factors were found to be significantly and independently associated with poor bowel function, namely, the pressure recorded in the upper part of the anal sphincter in response to distention of the neorectum (15 (7-24) cm of water in patients with poor function vs. 29 (15-58) cm in patients with good function; P < 0.005) and the level of the anastomosis above the anal sphincteric high pressure zone (2.5 (2 3.5) cm in patients with poor function vs. 6 (4-12) cm in patients with good function; P < 0.005). CONCLUSION: Continence after anterior resection is related to an appropriate "sampling" response in the anal sphincter to activity within the neorectum. This in turn, is directly related to length of the residual rectum, which is, therefore, of crucial importance to function. PMID- 7882789 TI - Fecal diversion for penetrating colon injuries--still the established treatment. AB - PURPOSE: An analysis of the existing literature on primary repair of colon injuries was undertaken to determine if there is sufficient evidence that this approach is superior to fecal diversion. METHODS: After a thorough literature search, three prospectively randomized studies comparing primary repair with fecal diversion in the management of colon injuries were identified. A variety of factors were examined, including the number of patients in each study arm, morbidity rates, as well as exclusion criteria. An analysis was performed to determine the number of patients required to establish statistical superiority of one procedure over the other. RESULTS: Pooling of the data contained in the aforementioned reports does not provide sufficient statistical power to support the superiority of primary repair of colon injuries. To demonstrate a 5 percent difference between the two approaches, a prospective, randomized study consisting of 200 patients in each arm is necessary. CONCLUSION: The present literature does not support a statistically valid advantage of primary repair over fecal diversion in the management of traumatic colon injuries. PMID- 7882790 TI - Natural history of minute sessile colonic adenomas based on radiographic findings. Is endoscopic removal of every colonic adenoma necessary? AB - PURPOSE: With the development of colonoscopy and double-contrast barium enema, detection of minute sessile colonic adenomas has increased. We evaluated progression of these lesions radiologically and attempted to clarify the natural history. METHODS: A total of 125 minute sessile adenomas (< or = 5 mm in size) with histologic confirmation were examined by double-contrast barium enema at an interval of more than one year. The average follow-up period was 24 (range, 12 36; standard deviation, 9.4) months. To allow for differences in magnification, adenomas increasing in size by 2 mm or more were defined as growing, and the other lesions were defined as unchanged. RESULTS: Eighty-six adenomas showed no interval change in size. Four adenomas decreased 1 mm in size, and 27 adenomas increased 1 mm in size. The remaining eight adenomas (6 percent) increased by 2 or 3 mm in size. None of the adenomas showed any morphologic changes. There was also no difference in degree of histologic atypia between growing and unchanged adenomas. None of the adenomas developed into carcinomas during the follow-up period. CONCLUSIONS: These data show that most minute sessile adenomas remain unchanged in size and morphology over the long term. Accordingly, these adenomas probably should be followed up radiologically or endoscopically to avoid excessive polypectomy. PMID- 7882791 TI - Intraoperative reasons for abandoning ileal pouch-anal anastomosis procedures. AB - PURPOSE: Ileal pouch-anal anastomosis (IPAA) has become the operation of choice for most patients with chronic ulcerative colitis and familial adenomatous polyposis. However, because of technical or disease factors at the time of pouch construction, IPAA must sometimes be abandoned. A retrospective review was conducted to find reasons for IPAA failure or abandonment. METHODS: Since 1981, 103 patients have had to have an IPAA procedure at the George Washington University Medical Center in Washington, DC. All charts were reviewed and data retrospectively collected. RESULTS: Six of 103 patients (six percent) were unable to have IPAA constructed. Five patients ultimately received a standard end ileostomy, and one had an ileorectal anastomosis. The reasons for abandoning the IPAA procedure were an ischemic pouch, failure to reach the anus, poorly controlled presacral hemorrhage, desmoid of the mesentery, and finding incurable colon carcinoma. CONCLUSIONS: Information regarding the risk of failure or abandonment during the IPAA procedure should be discussed with the patient during preoperative counseling and must be included as an element of informed consent. PMID- 7882793 TI - Patterns of male fecal incontinence. AB - PURPOSE: This study sought to identify clinical and manometric characteristics of male fecal incontinence. METHOD: Clinical charts of 25 men with a chief complaint of fecal incontinence were retrospectively reviewed. Their anorectal physiology test results were compared with those from a group of 20 healthy men. RESULTS: Fourteen men (56 percent) were "leakers," who complained of loss of liquid or solid stool smears that stained their underclothes. Eleven men (44 percent) had true incontinence, with loss of control over gas, liquid, and/or solid stool. Leakers had lower anal sphincter pressures than normal men (P < 0.05) but higher pressures than incontinent men (P < 0.05). In leakers the anal sphincter length at rest was longer than in incontinent (P < 0.01) and normal men (P < 0.05). All incontinent men had decreased manometric pressures, abnormal anorectal sensation or prolonged pudendal nerve terminal motor latencies, whereas only one-half of the leakers had physiologic abnormalities. Treatment using dietary manipulation, constipating agents or cleansing enemas was successful in nearly 90 percent of incontinent men but only 55 percent of the leakers. CONCLUSIONS: Whereas true incontinence in men is caused by a short, low pressure sphincter with altered sensation or innervation, leakage is associated with a long, intermediate pressure sphincter that frequently has normal sensation and innervation. This long, intermediate pressure sphincter may predispose these men to leakage. Treatment of leakers is less successful than treatment of incontinent men. Leakers and incontinent men have unique clinical and physiologic profiles that should be identified to help guide treatment and determine prognosis. PMID- 7882792 TI - Effect of omental pedicle hammock in protection against radiation-induced enteropathy in patients with rectal cancer. AB - PURPOSE: The aim of this nonrandomized study was to assess effects against radiation-induced enteropathy by constructing an omental pedicle hammock, thus isolating the small bowel outside the pelvis. METHODS: Since 1991, 32 patients received the omental pedicle hammock procedure as an adjunct to definitive cancer surgery, and the perioperative experiences and toxic effects of radiation therapy were evaluated and compared with 25 patients who received pelvic floor reperitonealization only. RESULTS: There were no surgical complications related to the omental hammock procedure. Contrary to control cases that showed the bowel to adhere deeply in the pelvis, exclusion of the small bowel from the pelvic cavity demonstrated by contrast study was successful in all except four cases of a segment of bowel loop descent within the radiation portals. According to acute and late radiation morbidity scoring criteria, 26 patients (81 percent) scored Grade 0 in the treatment group, whereas only 3 patients (12 percent) scored Grade 0 in the control group (P < 0.01) in the acute phase, and 28 patients (88 percent) of Grade 0 in the former group and 15 (60 percent) in the latter (P < 0.025) in late phase. There has been no case of radiation-induced enteropathy requiring surgical treatment. CONCLUSION: The technique of bowel exclusion by pedicle omental hammock would make it possible to use higher doses of postoperative pelvic radiation therapy without fear of complications from radiation-induced enteropathy. PMID- 7882794 TI - Social and sexual function following ileal pouch-anal anastomosis. AB - PURPOSE: Patients who undergo surgery for ulcerative colitis are usually young and active. When surgery becomes necessary, their future social and sexual function is of major concern. This study was performed to be able to give more detailed information of what is to be expected. METHODS: Forty-nine consecutive patients (26 men and 23 women) who underwent ileal J-pouch-anal anastomosis for ulcerative colitis between November 1983 and September 1986 in the authors' institution were personally interviewed regarding details of their preoperative and postoperative social and sexual functions. RESULTS: Eighty-eight percent had reduced capacity to work preoperatively compared with 6 percent postoperatively. Thirty-one percent resumed work in the period with diverting ileostomy. Leisure time activities were reduced in 47 percent preoperatively, whereas 6 percent had limitations postoperatively. In 35 percent of women, frequency of intercourse was increased postoperatively, and none reported a decreased frequency. None of the women who were able to achieve orgasm preoperatively reported a postoperative disturbance of this ability, and 16 percent experienced an increased quality of orgasm. Postoperatively none reported dyspareunia, vaginal discharge, or changes in their menstrual cycle. Frequency of intercourse and ability to achieve orgasm remained unchanged for the majority of men; however, one developed erectile dysfunction, and one complained of retrograde ejaculation. Sexual activity in men was less affected by the presence of an ileostomy, and 69 percent had intercourse in the period with ileostomy compared with 30 percent of women. None of the patients complained of anal pain, soiling, or fecal leakage during intercourse, but one women reported some discomfort from the pouch during intercourse. None of the patients wanted to return to a life with an ileostomy. CONCLUSION: The social and sexual function, quality of life, after ileal J-pouch anastomosis is improved when compared with the period with ulcerative colitis and the time with diverting ileostomy. In men, however, a frequency of sexual dysfunction similar to what is seen after proctectomy for benign diseases should be underlined. PMID- 7882795 TI - Mast cells in colorectal neoplasias and premalignant disorders. AB - PURPOSE: Mast cells have recently been found to be well correlated with the prognosis of patients with rectal cancer. This work aimed to characterize the role of mast cells in colonic premalignant conditions. METHODS: Mast cells were quantified in various colonic disorders, particularly those with premalignant potential. Possible avenues of mast cell action were investigated using these tissue samples, by measuring basement membrane and collagen layer thickening. RESULTS: The mean number of mast cells in carcinoma sections was 0.967/0.9 mm2, in various colorectal neoplasias and related conditions it ranged from 1.36-3/0.9 mm2, and in normal histologic specimens it was 11.90/0.9 mm2. These data established statistically significant differences in mast cell numbers in the colonic disorders studied. The number of mast cells is greatest in the lamina propria level of the colon, a site often not examined because of the limited depth of samples obtained from endoscopic biopsies. CONCLUSIONS: Mast cell numbers were found to be correlated to the development from premalignancy to colonic malignancy. Mast cells may be useful as markers of colorectal neoplasia. PMID- 7882796 TI - Pull-through procedures performed months to years after permanent proctectomy. AB - PURPOSE: Patients who have undergone proctectomy without concomitant rectal reconstruction or coloanal anastomosis were not normally considered candidates for re-establishment of anal continuity until a case report published in 1985. With the addition of nine patients, reported herein is a series of ten patients who have undergone delayed pull-through procedures months to years after permanent proctectomy. PATIENTS: Ten patients (including the single case reported in 1985) have undergone delayed pull-through procedures up to 24 years after permanent proctectomy and ostomy formation. Delayed ileal pouch-anal anastomoses were performed in nine patients, and delayed coloanal anastomosis was performed in one patient. There were four males and six females, each of whom had evidence of external sphincter contraction on physical examination. Average age was 33 (range, 24-51) years at the time of reconstruction. Average duration of follow-up is 32 (range, 1-96) months. RESULTS: One patient is awaiting ileostomy closure. Five of nine patients use constipating agents. Two patients are constipated and use enemas to aid in evacuation. None are wearing protective undergarments. One patient had his ileostomy reconstructed eight years after delayed pull-through for uncontrollable diarrhea associated with chemotherapy for multiple myeloma and recently died. Postoperative complications included wound infection (3), enterocutaneous anastomotic stricture requiring anoplasty (2), small bowel obstruction (1), pneumonia (1), presacral abscess (1), and pouchitis (1). CONCLUSIONS: Delayed pull-through procedures performed months to years after permanent proctectomy can be performed in selected patients, with results comparable to rectal reconstruction done at the time of proctectomy. PMID- 7882797 TI - Management of gastrointestinal bleeding after strictureplasty for Crohn's disease. AB - PURPOSE: To determine the incidence, clinical features, and optimal management of poststrictureplasty hemorrhage in Crohn's disease. METHODS: Retrospective analysis of 139 patients with Crohn's disease seen at the Cleveland Clinic who underwent a total of 523 strictureplasties between June 1984 and June 1992. RESULTS: Poststrictureplasty hemorrhage occurred in 13 patients (9.3 percent). Average drop in hemoglobin and hematocrit in these patients was 5.8 g/dl and 0.174, respectively. All patients were managed nonoperatively. Mean follow-up was 29.6 (range, 7-62) months. CONCLUSION: Strictureplasty in Crohn's disease is a safe procedure in selected patients. Poststrictureplasty hemorrhage is uncommon; however it can be managed nonoperatively in most cases. An algorithm for management of such patients is presented. PMID- 7882798 TI - Results of Delorme's procedure for rectal prolapse. Advantages of a modified technique. AB - PURPOSE: A retrospective study was undertaken to assess the results of Delorme's procedure for rectal prolapse and to determine the advantages of an innovative extended transrectal repair, which aims at performing a total pelvic floor repair. METHODS: A total of 85 patients, ranging in age from 21 to 97 years, were operated on. Sixty-five (82 percent) patients had varying degrees of fecal incontinence. Similar groups of patients were compared with regard to control of the prolapse and restoration of continence according to 1) age and medical condition and 2) operative technique: original vs. extended operation. RESULTS: Twelve patients (14 percent) developed postoperative complications. There was one perioperative death (1.2 percent). Eighty patients were followed for 6 to 136 (median, 33) months. Eleven (13.5 percent) developed recurrent full-thickness prolapse. The recurrence rate was significantly different 1) between 44 elderly and poor operative risk patients not suitable for abdominal surgery (22.5 percent) and 41 younger patients without concurrent medical conditions, electively submitted to perineal repair (5 percent) (P < 0.05), and 2) between the original procedure (21 percent of 44 patients) and the modified technique (5 percent of 41 patients) (P < 0.05). Forty five patients (69 percent) improved or regained full continence. No patient worsened. No residual dysfunction was induced. Restoration of continence was not influenced by selection of patients or surgical technique. CONCLUSIONS: Despite increased morbidity (22 percent; P < 0.05), advantages of the modified technique were 1) over the original procedure, a reduced recurrence rate, 2) over perineal proctectomy, the absence of coloanal anastomosis and better functional outcome, and 3) over abdominal rectopexy, a less aggressive approach without disturbing effects on bowel habits. PMID- 7882799 TI - Effects of octreotide on healing of intestinal anastomosis following small bowel obstruction in rats. AB - PURPOSE: Octreotide is an analog of somatostatin, with the same biologic effects but a longer half-life than somatostatin. The purpose of this experimental study was to search the effects of octreotide on the healing of bowel anastomosis and to observe the anatomic and physiologic changes in the obstructed bowel. METHODS: Two groups of ten male Wistar albino rats (average weight, 250 grams) were used in this study. One group was the octreotide group, and the other was the control group. In both groups, the basal diameters of jejunum were measured before ligation of the bowel 20 cm from the duodenum. Octreotide was administered subcutaneously (7 micrograms/kg/day, in two equal doses) in the first group, and the same volume of saline was used in the control group. Diameters of the obstructed segments were measured, and sodium and potassium levels, obtained from the luminal fluid of the obstructed bowel, were recorded 48 hours following the first operation. Dilated segments were resected, and end-to-end intestinal anastomoses were performed. In rats sacrificed on the fourth and seventh days following the second operation, bursting pressures of the anastomotic and hydroxyproline levels in tissue samples taken from the anastomosis were measured. RESULTS: The diameter of the obstructed bowel increased significantly in the control group (P < 0.05). Sodium and potassium losses were significantly less in the octreotide group (P < 0.001 for sodium; P < 0.01 for potassium). In histopathologic examination, ischemic changes were more evident in the control group (P < 0.05). Anastomotic bursting pressure differences were not significant on the fourth postoperative day (P > 0.05), but differences were significant on the seventh postoperative day (P < 0.05). Anastomotic tissue hydroxproline synthesis on the fourth and seventh postoperative days of the octreotide and control groups did not show significant difference (P > 0.05). CONCLUSION: In this experimental model, it appears that octreotide attenuates the ischemic changes and electrolyte losses in the obstructed bowel. PMID- 7882800 TI - Preoperative diagnosis of a small, depressed rectal cancer complicating ulcerative colitis. Report of a case. AB - PURPOSE: This study was designed to clarify the importance of detecting small, depressed colorectal cancer complicating ulcerative colitis. METHODS: A 39-year old Japanese male, who had an 18-year history of left-sided ulcerative colitis, was admitted to Fukuoka University Hospital for further evaluation of his colitis. Colonoscopy with a dye spraying method clearly revealed a small, depressed lesion and flat plaque-like lesions in the rectum. Biopsies taken from a depressed lesion and plaque-like lesions revealed a signet-ring cell carcinoma and dysplasia, respectively. Total colectomy was performed. RESULTS: Sections from the depressed rectal lesion, measuring 7 x 8 mm in size, revealed a signet ring cell carcinoma that diffusely invaded the muscularis propria. Lymph node metastasis was evident. Flat plaques and mucosa around the depressed lesion were positive for dysplasia. CONCLUSION: This is the first report of a case of small, depressed rectal cancer complicating ulcerative colitis diagnosed by preoperative colonoscopy. To improve outcome of colonoscopic surveillance in ulcerative colitis, detecting such small, depressed lesions are important, and colonoscopy with a dye spraying method would be useful in detecting them. PMID- 7882801 TI - Colorectal manifestations of endocrine disease. AB - PURPOSE: The aim of this review is to alert the colon and rectal surgeon to the colorectal manifestations of endocrine disease. METHODS: This report was obtained by a review of the medical literature. Endocrine disease may initially present as a symptom felt to be referable to colorectal disease. Furthermore symptoms of well-established endocrine disorders may have refractory colorectal symptoms. RESULTS: Constipation is the most common gastrointestinal symptom of diabetics; however, in patients with brittle diabetes, diarrhea may be chronic and intermittent. Unexplained diarrhea, despite an exhaustive work-up for an etiology, should alert the clinician to the possibility of a pancreatic endocrine tumor. Thyroid disorders, depending on activity of the gland, may have refractory constipation, diarrhea, or steatorrhea as the only presenting symptoms. Constipation is a common symptom of hypercalcemia, secondary to hyperparathyroidism. Primary hyperparathyroidism has been associated with increased incidence of malignancies, specifically of colonic origin. In patients with acromegaly a threefold to eightfold increased risk of colon carcinoma or adenomatous polyps is seen. Chronic adrenal insufficiency may present initially as diarrhea and malabsorption. The adrenal gland is a frequent site of metastases from colorectal cancer. Pheochromocytomas may be a cause of occult gastrointestinal bleeding or ischemic colitis. CONCLUSION: Unexplained symptoms referable to the colon and rectum should alert the clinician to the possibility of an underlying endocrine disorder. PMID- 7882802 TI - Laparoscopic-assisted mini laparatomy with colectomy. AB - PURPOSE: Laparoscopic colectomy, as many claim, is technically feasible. However, none can definitely attest to its superiority over or even equivalence to traditional open laparotomy. The goal of this study is to assess results of laparoscopic colectomy via a new approach compared with traditional colectomy. METHODS: The study involves 12 cases of laparoscopic mini laparotomy with colectomy and another 12 cases of traditional colectomy. Laparoscopic mini laparotomy is performed with the same equipment used in laparoscopic cholecystectomy. Through a small 5-cm to 6-cm incision, the surgeon's left hand inserts into the peritoneal cavity and participates in the laparoscopic mobilization of the bowel along with other laparoscopic instruments. Mesenteric division and bowel anastomosis are performed through the same incision extracorporeally. RESULTS: The preliminary result of the study shows that, compared with traditional surgery, laparoscopic mini laparotomy with colectomy offers reduction in the frequency of usage of intramuscular analgesics, better cosmetic results, earlier food intake, and shorter hospital stay. The only disadvantage of laparoscopic mini laparotomy with colectomy is that it takes longer operative time, which may decrease with more experience. CONCLUSION: Laparoscopic mini laparotomy with colectomy is an alternative method of laparoscopic colectomy. It seems to offer a similar morbidity and better results compared with colectomy in open laparotomy. PMID- 7882803 TI - Transanal excision of rectal tumors using a laparoscopic stapler. AB - A successful method for transanal excision of low-lying rectal tumors is described. With the use of laparoscopic staplers, these tumors can be completely and safely excised and adequate hemostasis obtained. PMID- 7882804 TI - Different strokes for different folks in repair of rectal prolapse. PMID- 7882805 TI - Cancer recurrence after laparoscopic colectomy--a missing link? PMID- 7882806 TI - Environmental factors in childhood IDDM. A population-based, case-control study. AB - OBJECTIVE: To identify environmental factors involved in the etiology of insulin dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: An estimated 90% of all incident cases of IDDM in patients 0-14 years of age in New South Wales, Australia, were ascertained over 18 months. For each IDDM patient, two age- and sex-matched control subjects were randomly selected from the population. Past environmental exposures were determined with a questionnaire completed by the parents. Response rates were 92% for the IDDM patients (217 of 235) and 55% for the control subjects (258 of 470). The relative risk associated with each exposure was estimated with the odds ratio (OR) adjusted for confounding factors using multiple logistic regression. RESULTS: The introduction of cow's milk-based infant formula into the diet before 3 months of age was associated with an increased risk (OR 1.52, 95% confidence interval [CI] 1.04-2.24). Exclusive breast-feeding for > or = 3 months was associated with a protective effect (OR 0.66, 95% CI 0.45-0.97). High dietary intake of cow's milk protein in the 12 months before the onset of diabetic symptoms was also associated with an increased risk (OR 1.84, 95% CI 1.12-3.00). A recent infection (during the 3 months before onset of diabetic symptoms) was more common in the patients than the control subjects (OR 2.92, 95% CI 1.96-4.35), as was day care attendance before the age of 3 (OR 1.73, 95% CI 1.00-3.00). When two age-groups, defined by the median age at onset of diabetes, were compared, the associations with early infant-feeding were stronger among the younger group (< 9.2 years), and associations with recent diet and recent infection were stronger among the older group (> or = 9.2 years). CONCLUSIONS: These results indicate an increased risk of IDDM associated with early dietary exposure to cow's milk-containing formula, short duration of exclusive breast-feeding, high intake of cow's milk protein in the recent diet, recent infection, and early attendance at day care. PMID- 7882807 TI - Long-term glycemic control has a nonlinear association to the frequency of background retinopathy in adolescents with diabetes. Follow-up of the Berlin Retinopathy Study. AB - OBJECTIVE: To assess the influence of long-term glycemic control on the development of background retinopathy in adolescents followed longitudinally from the onset of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Repeated retinal fluorescein angiographies, in intervals of 1-2 years, were evaluated prospectively in 346 patients (190 males, 156 females; 19.8 [8.8 35.4] years of age; diabetes duration of 10.4 [1.1-27.4] years at their latest eye examination, median [range]). The influences of long-term HbA1c (mean of 18 [1-95] determinations per person) and microalbuminuria (> or = 2 of > or = 3 measurements > or = 15 micrograms/min x 1.73 m2) were studied by multiple linear regression, life-table analysis, and trend analyses. RESULTS: The rate of background retinopathy per 100 patient-years increased with poorer glycemic control from 0.7 (long-term HbA1c < 7% to 7.3 (HbA1c > 11%) following an exponential function. Life-table analysis after subdivision in HbA1c quartiles of equal sizes (HbA1c < 8, 8-9, 9-10, and > 10%) revealed an individual median expectation of background retinopathy after more than 25, 16.2, 12.7, or 12.0 years of diabetes, respectively. However, significant differences were found only between 8-9% and 9-10%, calculated either as prevalence, life-table analysis, or relative incidence, thus suggesting that a threshold model may also fit the data. After 12 years of diabetes, < 25% of those patients exhibiting microalbuminuria (n = 18) were expected to be free from retinopathy compared with 81% of those with normoalbuminuria (n = 86). CONCLUSIONS: Two statistical models are appropriate to explain the relationship between glycemic control and risk for background retinopathy: 1) a continuous exponential relationship as described by the DCCT or 2) the presence of a threshold HbA1c level at 9%. Thus, diabetes treatment in children should aim at long-term HbA1c levels < 9.0%, but every progress closer to normal may further reduce the risk. PMID- 7882808 TI - Hypoglycemia unawareness in IDDM. AB - OBJECTIVE: To assess the characteristics of patients with hypoglycemia unawareness (development of neuroglycopenia without appropriate prior autonomic warning symptoms) and its predisposing factors. RESEARCH DESIGN AND METHODS: We studied 43 insulin-dependent diabetes mellitus patients who were objectively categorized as having or not having hypoglycemia using the stepped hypoglycemic clamp technique in which plasma glucose was clamped at plateaus of 4.3, 3.6, 3.0, and 2.3 mmol/l and a statistical criterion (onset of autonomic warning symptoms at a plasma glucose concentration 2 SD below normal) and examined their clinical characteristics and hormonal, symptomatic, and cognitive responses. RESULTS: Eleven (26%) of the patients were classified as having hypoglycemia unawareness. Compared with the other patients, unaware patients had a lower HbA1c level (P < 0.01), a longer duration of diabetes (P < 0.01), and a history of more severe hypoglycemia (P < 0.003). During experimental hypoglycemia, counterregulatory hormone responses, neuroglycopenic symptoms, and cognitive dysfunction all began at lower plasma glucose concentrations in unaware patients (P < 0.01, 0.03, and 0.01, respectively). Moreover, although the magnitudes of their plasma catecholamine responses and autonomic symptoms were reduced (both, P < 0.01), the plasma catecholamine levels at which autonomic symptoms began was not altered. Finally, as seen from glucose infusion rates necessary to maintain identical plasma glucose levels, patients with hypoglycemia unawareness had increased sensitivity to insulin (P < 0.001). CONCLUSIONS: Our results confirm an association between hypoglycemia unawareness and duration of diabetes, glycemic control, and occurrence of severe hypoglycemia, and in addition provide evidence that both autonomic and neuroglycopenic symptoms are affected and that insulin sensitivity is increased, but beta-adrenergic sensitivity is not diminished. PMID- 7882809 TI - Diabetic nephropathy and microalbuminuria in the community. The South Auckland Diabetes Survey. AB - OBJECTIVE: To compare the clinical, anthropometric, and metabolic characteristics of New Zealand Europeans, Maori, and Pacific Islanders with non-insulin-dependent diabetes mellitus (NIDDM) with emphasis on risk factors for the development of diabetic nephropathy. RESEARCH DESIGN AND METHODS: A cross-sectional survey of 555 (74% of 750 available) diabetic patients attending diabetes clinics and randomly selected primary care centers was conducted in Auckland, New Zealand. RESULTS: Among those with NIDDM, Maori and Pacific Islanders were younger at diagnosis, more obese, and had poorer glucose control when compared with the Europeans (fructosamine in mumol/l: Maori 335 +/- 78, Pacific Islanders 367 +/- 90, Europeans 318 +/- 55; overall P < 0.001). Systolic blood pressure (sBP) was higher in Maori (145 +/- 31 mmHg) and lower in Pacific Islanders (135 +/- 25 mmHg) when compared with Europeans (141 +/- 25 mmHg; overall P < 0.005). Mean estimated daily urinary albumin excretion (UAE) was 18.2 (15.5-1.3) mg/day in Europeans, 94.8 (60.5-148.7) mg/day in Maori, and 44.2 (32.3-60.3) mg/day in Pacific Islanders. The prevalence of proteinuria and end-stage renal failure were also higher in Maori and Pacific Islanders. The excess prevalence of microalbuminuria and proteinuria in Maori was present within 5 years of diagnosis. Europeans with impaired renal function were least likely to have associated proteinuria or microalbuminuria. Microalbuminuria and nephropathy were not consistently associated with either higher blood pressure or worse glucose control. CONCLUSIONS: NIDDM in Maori and Pacific Islanders is associated with a greater degree of proteinuria and end-stage renal failure than that in Europeans. This observation is not explained by conventional risk factors. PMID- 7882810 TI - Postural instability in patients with diabetic sensory neuropathy. AB - OBJECTIVE: Recent survey evidence suggests that sensory ataxia due to diabetic neuropathy may be a more frequent and serious problem than is commonly recognized. This view is further supported by research that confirms the major contribution of the somatosensory system to the control of posture. We therefore sought to determine the effects of significant diabetic distal symmetrical polyneuropathy on the control of posture. RESEARCH DESIGN AND METHODS: Fifty-one subjects, divided into three groups, participated in this study. Seventeen had diabetes and significant sensory neuropathy, 17 had diabetes and no neuropathy, and 17 had neither diabetes nor neuropathy. The subjects were matched across groups, and stringent exclusion criteria were applied. Postural stability during quiet standing was measured using a force platform. In addition to electrophysiological and quantitative sensory tests of neuropathy, a number of physical and functional characteristics were measured for all subjects. RESULTS: Postural instability was found to be significantly associated with sensory neuropathy, but not with diabetes per se. Patients with sensory neuropathy demonstrated between 66 and 117% more instability than did control subjects (depending on the testing condition). Based on multiple linear regression analyses, the most significant correlates of instability were the quantitative sensory measures of neuropathy and age. CONCLUSIONS: The loss of sensory perception secondary to diabetic distal symmetrical sensory neuropathy has a markedly detrimental effect on postural stability. The deficit is greatest when visual or vestibular cues are absent or degraded. Patients with neuropathy need to be informed of the postural consequences of this condition to limit the potential morbidity caused by falls. PMID- 7882811 TI - Peripheral autonomic impairment in patients newly diagnosed with type II diabetes. AB - OBJECTIVE: To measure both peripheral and central autonomic function in patients newly diagnosed with type II diabetes. RESEARCH DESIGN AND METHODS: Measurements were made on 49 diabetic patients (8 with long-standing diabetes and neuropathic complications, 41 with newly diagnosed type II diabetes) and on 49 healthy, age- and sex-matched, control subjects. Five of the 41 newly diagnosed type II diabetic patients had retinopathy, and 4 had clinical evidence of neuropathy. No patient or control subject had significant vascular disease. Cardiac autonomic function was investigated by using standard cardiovascular reflex tests. The digital vasoconstrictor responses to deep breathing and body cooling were measured using venous occlusion plethysmography. RESULTS: The vasoconstrictor responses to a deep breath and body cooling were significantly reduced (P < 0.001) in the fingers and toes of the neuropathic patients compared with their matched control subjects, as were the heart rate responses (P < 0.02). The vasoconstrictor responses were significantly reduced in the toes (P < 0.001) and fingers (P < 0.05, P < 0.01) of the newly diagnosed patients compared with the corresponding responses in the control subjects. There was no significant difference in the heart rate or blood pressure responses of these patients and control subjects during standard tests of cardiac autonomic function. CONCLUSIONS: Patients with type II diabetes may have impaired peripheral autonomic function at diagnosis. PMID- 7882813 TI - Reliability and validity of cardiovascular and vasomotor autonomic function tests. AB - OBJECTIVE: To determine the reliability and validity of autonomic function tests (AFTs) as clinical tools for diagnosing diabetic autonomic dysfunction. RESEARCH DESIGN AND METHODS: Twenty-one healthy control subjects and 21 insulin-dependent diabetes mellitus (IDDM) patients (11 with no symptomatology and 10 with symptomatic diabetic autonomic neuropathy [DAN]) were matched for age, and administered three standard cardiovascular tests and two new vasomotor tests of autonomic function. Each of the cardiovascular tests (change in heart rate [delta bpm], Valsalva ratio [VR], change in systolic blood pressure [delta sBP]) and vasomotor tests (total pulse amplitude [TPA] and percent vasoconstriction [%VC]) were repeated within 1 week. Infrared photoplethysmography measured sympathetic mediated vasomotor function. Reliability was determined by intraclass correlation coefficients. Validity was determined by analysis of variance procedures to test for differences between known groups and by computing sensitivity, specificity, and positive and negative predictive values. RESULTS: All AFTs were reliable, with %VC having highest reproducibility (r = 0.90). AFT scores were not different from time 1 to time 2. After controlling for age, two cardiovascular tests had significantly different values for control subjects and asymptomatic diabetic patients. AFTs, except delta sBP, were significantly different between symptomatic diabetic patients and asymptomatic diabetic patients after controlling for age and duration of disease simultaneously. Sensitivity, specificity, and predictive values for %VC were comparable to the values for delta bpm and VR. TPA indexes were lower but clinically acceptable. CONCLUSIONS: AFTs were found to be reliable and valid tests for detecting DAN. TPA and %VC are important because they measure an aspect of sympathetic function not assessed by standard cardiovascular AFTs, and they do not depend on the patient's cooperation or ability to exert effort. PMID- 7882812 TI - Diabetes with mitochondrial gene tRNALYS mutation. AB - OBJECTIVE: To solve a possible relationship between mtDNA mutation of tRNALYS(8344) and diabetes, we have surveyed the tRNALYS mutation, glucose intolerance, and insulin secretory capacity in a Japanese family with diabetes and myoclonic epilepsy with ragged-red fiber disease. Several lines of evidence suggested possible linkage between mtDNA mutation and diabetes (1-4). RESEARCH DESIGN AND METHODS: DNA was isolated from peripheral lymphocytes. The polymerase chain reaction analysis for the tRNA(LYS)(8344) mutation of the mtDNA was conducted as described by Larsson (5). Insulin secretory capacity was assessed by 24-h urinary C-peptide immunoreactivity response (CPR) excretion and plasma CPR to glucagon administration. RESULTS: We identified seven subjects with the tRNA(LYS) mutation as well as seven non-mutated members in the pedigrees. Oral glucose tolerance tests in the pedigree indicated that five of the mutated subjects were diabetic, one had impaired glucose tolerance, and one had normal glucose tolerance (NGT), whereas all nonmutated family members had NGT. The pedigree shows maternal transmission of diabetes and the tRNA(LYS) mutation over three generations. Twenty-four-hour urinary excretion of CPR was significantly reduced in the mutant subjects (mean +/- SD, 67.8 +/- 79.2 nmol/day, n = 6, P < 0.001) compared with the nonmutant members (276.6 +/- 41.8 nmol/day, n = 5) and the age-matched normal control subjects (263 +/- 64.3 nmol/day, n = 12). Plasma CPR 6 min after glucagon injection demonstrated a marked reduction in the mutant subjects (3.68 +/- 3.45 nmol/l, n = 5, P < 0.001) compared with the nonmutant members (19.4 +/- 1.17 nmol/l, n = 5) and the normal control subjects (15.8 +/- 3.81 nmol/l, n = 12). Bilateral neurosensory deafness was demonstrated in five of seven (71.4%) mutant subjects (five of five [100%] mutated diabetic patients), but not detected in six nonmutant members. CONCLUSIONS: This observation is the first report of association of diabetes with the mitochondrial tRNA(LYS) mutation. Insulin secretory capacity was significantly lower in the mutant members than in the nonmutated members. These findings suggest that the pancreatic beta-cell secretory defect of insulin might be one of the phenotypes of the mitochondrial tRNA(LYS) mutation. PMID- 7882814 TI - The prevalence of NIDDM and associated coronary risk factors in Mexico City. AB - OBJECTIVE: To determine the prevalence of diabetes and associated coronary risk factors in the Mexico City population. RESEARCH DESIGN AND METHODS: A sample of 805 adults was selected from Mexico City. The participants, 20-90 years of age and living in the city, were selected by the method of multistage cluster sampling with proportional allocation. Diabetes was diagnosed by previous history or if fasting blood glucose was > or = 7.8 mmol/l ( > or = 7.8 mmol/l ( > or = 140 mg/dl). RESULTS: The crude rate prevalence of NIDDM was 8.7%, with an age adjusted rate of 10.6% for women and 6.0% for men. Age strongly influenced diabetes prevalence, with a chi 2 of risk tendency of 39.1 (P < 0.00005). A significant proportion (5.9%) of younger individuals (35-44 years of age) was affected by the disease. Diabetes was associated with advanced age, had a greater impact in the low-income group, and showed increased odds ratio for hypertension, dyslipidemias, and myocardial infarction in men and women and for obesity only in women. CONCLUSION: There is a high prevalence of NIDDM in Mexico City that also strikes a significant group of younger individuals. Associated coronary risk factors are also common and more prevalent in diabetic individuals. Current epidemiological data in Mexico and Mexican-Americans in the U.S. suggest that we may be on the ascending limb for diabetes and cardiovascular disease. There is a critical need for resources to be allocated to programs for primary and secondary prevention, which must be well structured and organized so that proper standards of care are followed to prevent progression of the disease. PMID- 7882815 TI - Beneficial effect of chromium supplementation on serum triglyceride levels in NIDDM. AB - OBJECTIVE: To investigate the effect of chromium picolinate supplementation on the lipid profile of the predominantly Hispanic population of non-insulin dependent diabetes mellitus (NIDDM) patients in San Antonio, Texas. RESEARCH DESIGN AND METHODS: A prospective, double-blind, placebo-controlled, crossover study was performed on 14 men and 16 women. Initially, each patient was randomly assigned to receive either chromium picolinate or placebo for 2 months. This initial treatment phase was followed by a 2-month washout period. Subjects were then crossed-over and received the alternate capsule for an additional 2 months. Fasting blood glucose, HbA1c, and serum lipids were compared at the end of each treatment phase. RESULTS: Twenty-eight of the originally enrolled 30 patients completed the study. There were no adverse reactions to chromium reported. There were no differences noted between the control and chromium-treated subjects in glucose control, high-density lipoprotein cholesterol levels, or low-density lipoprotein cholesterol levels. Triglyceride (TG) levels were reduced significantly (17.4%; P < 0.05) during the 2 months of chromium supplementation. CONCLUSIONS: Ours is the first report of a significant reduction in serum TGs in a group of NIDDM patients treated with chromium. The low cost and excellent safety profile of chromium make it an attractive lipid-lowering agent for this population. Long-term studies are needed to determine if the short-term changes in plasma lipids can be sustained. PMID- 7882816 TI - Effect of added fat on the plasma glucose and insulin response to ingested potato given in various combinations as two meals in normal individuals. AB - OBJECTIVE: In normal subjects, ingestion of fat with potato in a morning meal resulted in a decrease in the glucose response. Therefore, we wished to determine whether a fat-induced decrease in blood glucose also would be observed after a second identical meal. In addition, we were interested in determining if fat ingestion with a morning meal would have an effect on the blood glucose and insulin responses to a second meal not containing fat. RESEARCH DESIGN AND METHODS: Nine healthy male subjects ingested two meals consisting of an amount of potato containing 50 g carbohydrate, either alone or with 50 g fat as butter. The meals were served in four combinations as follows: 1) potato for the first meal, potato for the second meal; 2) potato for the first meal, potato with fat for the second meal; 3) potato with fat for the first meal, potato for the second meal; and 4) potato with fat for the first meal, potato with fat for the second meal. Meals were ingested at 8:00 A.M. and noon. Plasma glucose and C-peptide, serum insulin, triglyceride, and free fatty acid (FFA) concentrations were determined over an 8-h period. The integrated area responses to the meals were quantified over the subsequent 4-h period using the fasting value or the noon value as baseline for the first and second meals, respectively. RESULTS: When the first meal contained potato only, the glucose area response to the second meal was significantly less when the second meal contained fat. However, fat ingestion had no effect on the glucose area response to the second meal when fat was present in the first meal. The insulin area responses to the first and second meals were similar after ingestion of potato or potato with fat. However, the insulin response to the second meal always was less than that to the first meal. The C peptide area responses after ingestion of the second meal also were all higher than those after the first meal. The triglyceride area responses were slightly negative after ingestion of potato alone in the first meal. When fat was ingested, they were positive. When the first meal contained fat but the second meal did not, there was a rise in triglyceride concentration after the second meal as well as after the first meal. That is, a rise occurred without ingestion of fat with the second meal. If fat was present in the second meal the rise was even greater. The FFA area responses were similar to the triglyceride area responses. CONCLUSIONS: When fat was ingested with carbohydrate in either the first or second meal, the glucose area response was decreased. However, when both meals contained fat, a decrease in the glucose area response did not occur with the second meal. The glucose area responses all were greater after the second meal compared with those after the first meal, i.e., the opposite of a Staub Traugott effect was observed. The insulin area responses to the first and second meals were similar whether fat was ingested or not. PMID- 7882818 TI - Urinary chiro-inositol excretion is an index marker of insulin sensitivity in Japanese type II diabetes. AB - OBJECTIVE: To determine the relationship between urinary chiro-inositol excretion and insulin sensitivity in Japanese type II diabetic patients. RESEARCH DESIGN AND METHODS: Eighteen subjects were age-matched, nonobese, type II diabetic patients. Eight subjects had impaired glucose tolerance (IGT), and 10 had normal glucose tolerance (NGT). We quantified urinary chiro-inositol excretion using gas chromatography-mass spectrometry and the insulin sensitivity index (SI), and glucose effectiveness (SG) using Bergman's modified minimal model method. RESULTS: The urinary excretion of chiro-inositol was much lower in the diabetic patients (32.3 +/- 16.0 mumol/day, means +/- SD) than in the NGT subjects (96.0 +/- 17.6; P < 0.0001) and IGT subjects (58.9 +/- 11.6; P < 0.0001). SI was much lower in the diabetic patients (3.81 +/- 1.49) than in the NGT subjects 6.30 +/- 1.59, P < 0.0005). SG was much lower in the diabetic patients (2.14 +/- 0.56) than in the NGT subjects (3.07 +/- 0.38, P < 0.0001). There was a significant correlation between urinary chiro-inositol excretion and SI (r = 0.766), as well as a significant correlation between urinary chiro-inositol excretion and SG (r = 0.747). PMID- 7882817 TI - Comparative efficacy of a once-daily controlled-release formulation of glipizide and immediate-release glipizide in patients with NIDDM. AB - OBJECTIVE: To compare the efficacy and safety of controlled-release glipizide (glipizide-GITS [gastrointestinal therapeutic system]) and immediate-release glipizide in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: In a multicenter, open-label, randomized, two-way crossover study, 132 patients with NIDDM received daily doses of 5, 20, or 40 mg of either glipizide-GITS or immediate-release glipizide for 8 weeks followed by 8 weeks of the alternate formulation. Plasma glucose, serum insulin, C-peptide, and plasma glipizide levels were measured at fasting and post-Sustacal challenge at the end of 1 and 8 weeks of each treatment phase. HbA1c was measured at the end of weeks 7 and 8 of each treatment phase. RESULTS: Both formulations of glipizide yielded similar mean HbA1c values. However, mean fasting plasma glucose (FPG) levels were significantly lower with glipizide-GITS treatment than with immediate release glipizide at the end of week 1 (11.0 vs. 11.6 mmol/l; P < 0.01) and at the end of the 8-week treatment phase (10.9 vs. 11.7 mmol/l; P < 0.001). Fasting insulin and C-peptide levels were lower after 5 mg glipizide-GITS vs. immediate release glipizide. Glucose responses to Sustacal were similar after both formulations of glipizide; however, serum insulin (P < 0.01) and C-peptide responses (P < 0.05) were lower with glipizide-GITS than with immediate-release glipizide treatment at the end of the 8-week treatment phase. Mean plasma glipizide concentrations were stable by the end of week 1, and the concentrations increased proportionately with dose. Once-daily Glipizide-GITS provided effective mean glipizide concentrations (> 50 ng/ml) 24 h after dosing, even at the lowest (5 mg) dose level. Both formulations were well tolerated. CONCLUSIONS: Glipizide GITS was significantly more effective than immediate-release glipizide in reducing FPG levels. Both formulations reduced postprandial plasma glucose levels equally; however, glipizide-GITS exerted its control in the presence of lower plasma glipizide concentrations in addition to significantly lower insulin and C peptide levels. This suggests that glipizide-GITS improves insulin sensitivity. PMID- 7882819 TI - Diet and exercise in the treatment of NIDDM. The need for early emphasis. AB - OBJECTIVE: To investigate the effectiveness of an intensive diet and exercise program for controlling non-insulin-dependent diabetes mellitus (NIDDM) and reducing risk factors associated with macrovascular complications. RESEARCH DESIGN AND METHODS: Medical charts obtained from 4,587 participants in a lifestyle modification program were screened for patients with NIDDM. A total of 652 patients was identified, and their responses to the 3-week program were analyzed. RESULTS: Fasting glucose level was reduced from 10.0 to 8.45 mmol/l, and 71% of 197 subjects taking oral hypoglycemic agents and 39% of 212 taking insulin were able to discontinue their medication. Of the 243 not taking medication, 76% reduced their fasting glucose levels to < or = 7.84 mmol/l. Blood pressure was significantly reduced, and of the 319 initially taking antihypertension drugs, 34% had their medication discontinued. Serum total and low-density lipoprotein cholesterol were reduced by 22% and triglycerides by 33%. The ratio of total to high-density lipoprotein cholesterol was reduced by 13%. CONCLUSIONS: Lifestyle modification consisting of diet combined with aerobic exercise can be effective for controlling NIDDM and reducing risk factors associated with macrovascular complications in both men and women. The program was far more effective in controlling the disease in patients taking no medication or oral agents compared with patients taking insulin. These results stress the need for early emphasis on lifestyle modification in the treatment of NIDDM. PMID- 7882820 TI - The incidence of IDDM in Seoul from 1985 to 1988. AB - OBJECTIVE: To determine insulin-dependent diabetes mellitus (IDDM) incidence rates for the first time in Seoul, Korea, from 1985 to 1988. RESEARCH DESIGN AND METHODS: A mail survey was conducted among all hospitals, a total of 136, with > 80 beds in the Seoul area. Of these, (15.4%) hospitals reported patients with newly diagnosed IDDM. RESULTS: The average incidence rate of IDDM from 1985 to 1988 was 0.70/100,000 (95% confidence interval [CI]: 0.55-0.89). When stratified by gender, the average incidence rate in boys was 0.58/100,000 (95% CI: 0.42 0.9), and in girls it was 0.78/100,000 (95% CI: 0.56-1.07). The age at onset was similar to that reported in other countries, i.e., more than 50% of the cases were diagnosed between the ages of 10 and 14. The incidence of IDDM increased in parallel with the age-group (0.4 < 5-9 < 10-14 years). Onset seasonality was also similar to that in other reported countries with the most cases occurring during the winter months and the least number of cases during the summer months. CONCLUSIONS: The incidence rate of IDDM in Seoul is the lowest reported in the world. This might be effectively considered a baseline incidence rate before exposure to environment or other risk factors. The similar pattern of onset characteristics in Korea to those in other countries suggests that the same etiological factors are operative. PMID- 7882821 TI - Effect of fosinopril on cardiac and metabolic parameters in patients with NIDDM. AB - OBJECTIVE: To determine whether the angiotensin-converting enzyme (ACE) inhibitor fosinopril can favorably alter cardiac function in non-insulin-dependent diabetes mellitus NIDDM) patients who have either normal blood pressure (BP) or mild, untreated hypertension. RESEARCH DESIGN AND METHODS: Fifty-five NIDDM subjects with normal BP or mild, untreated hypertension were randomized to treatment with the ACE-inhibitor fosinopril or placebo for 6 months in a randomized, double blind trial to determine the effect of fosinopril on echocardiographic measurements. RESULTS: Left ventricular mass index (LVMI) fell by 6.5 +/- 4.7% (mean +/- SD) with fosinopril and increased by 8.6 +/- 3.5% during placebo treatment (P < 0.02), and isovolumic relaxation time improved significantly in those with elevated baseline levels (P = 0.02). Systolic BP fell significantly, but this did not correlate with the change in LVMI, suggesting a possible direct action of fosinopril on the heart. CONCLUSIONS: Fosinopril appears to have significant cardiac benefits in patients with NIDDM who have normal or mildly elevated BP. These benefits are achieved without adversely affecting renal status and without impairing metabolic control of diabetes. PMID- 7882822 TI - Glucokinase gene variations in Japanese-Americans with a family history of NIDDM. AB - OBJECTIVE: To determine if sequence variants in the glucokinase (GCK) gene contribute to the high risk of impaired glucose metabolism in Japanese-Americans and whether the gene sequence differs between Japanese-Americans and Caucasians. RESEARCH DESIGN AND METHODS: Forty-seven unrelated Japanese-Americans with one or more first-degree relatives with non-insulin-dependent diabetes mellitus (NIDDM) were selected, irrespective of glucose tolerance status. By World Health Organization criteria, 13 had normal glucose tolerance, 11 had impaired glucose tolerance, and 23 had NIDDM. Variations in the GCK gene were identified by single strand conformation polymorphism analysis and sequenced using standard techniques. RESULTS: Six variants of the GCK gene were identified in a total of 21 subjects: 1) a G--> A substitution at nucleotide -30 in the beta-cell-specific promoter; 2) an A--> G substitution at nucleotide 244 in the 5'-untranslated region (5'-UTR) of exon 1a; 3) a C--> G substitution at nucleotide 403 in the 5' UTR of exon 1a; 4) a G--> A variant 13 base pair (bp) 5' to the intron 3 exon 4 junction; 5) a silent substitution in the third base of codon 145 in exon 4; and 6) a C--> T substitution 8 bp 3' to the exon 9 intron 9 junction. None of these variations would be expected to affect the structure of the GCK enzyme. While none of these variants were significantly associated with IGT or NIDDM, a nonsignificant increase in the beta-cell promoter variant was observed in subjects with abnormal glucose tolerance. No uniform sequence differences in the GCK gene were identified between Japanese-American and Caucasian-American subjects. CONCLUSIONS: Mutations affecting the amino acid sequence of GCK do not account for the increased incidence of impaired glucose metabolism in Japanese Americans, and the gene sequence does not uniformly differ from that in Caucasians. PMID- 7882823 TI - Enhanced pressor responsiveness to norepinephrine in type II diabetes. Effect of ACE inhibition. AB - OBJECTIVE: To evaluate the effect of angiotensin-converting enzyme (ACE) inhibition on the pressor responsiveness to norepinephrine in type II diabetes. RESEARCH DESIGN AND METHODS: Eight normotensive subjects, eight mild-to-moderate hypertensive type II diabetic patients, and eight nondiabetic patients with essential hypertension were studied before and after 4 weeks of being administered enalapril. The pressor response to norepinephrine was assessed by infusing the hormone in an antecubital vein at incremental doses of 30 ng.kg 1.min-1 for periods of 5 min until reaching an increase of 20 +/- 2 mmHg in mean arterial pressure (MAP) measured by an automatic device at 1-min intervals. An effective dosage of norepinephrine that increased MAP by 20 mmHg (EDNE 20) was thereafter calculated. Before and during the last minute of norepinephrine infusion at maximum dosage, a venous blood sample was drawn to determine plasma renin activity (PRA), aldosterone, and norepinephrine levels. RESULTS: In the three groups of patients, blood pressure and aldosterone were reduced while PRA was raised following ACE inhibition. Basal and maximum postinfusion levels of norepinephrine were not modified by enalapril. The EDNE 20 was basally lower in diabetic patients and remained unchanged after ACE inhibition, contrary to that observed in nondiabetic patients with essential hypertension. CONCLUSIONS: Both normotensive and hypertensive type II diabetic patients have an increased pressor responsiveness to norepinephrine that is not modified by therapeutic doses of enalapril, contrary to what is observed in nondiabetic patients with essential hypertension. PMID- 7882824 TI - Relationship between dairy product consumption and incidence of IDDM in childhood in Italy. AB - OBJECTIVE: To test the hypothesis that the consumption of dairy products, including fluid cows' milk and cheese, is related to the incidence of insulin dependent diabetes mellitus (IDDM), we correlated incidence rates in children 0 14 years of age with cows' milk and cheese consumption in nine regions of a single country, Italy. RESEARCH DESIGN AND METHODS: Data on the incidence of IDDM were derived from the only nine Italian regions where primary and secondary sources of ascertainment were available for 1991. Data on fluid cows' milk and cheese consumption in the corresponding year in each region were obtained from the National Institute of Statistics. RESULTS: The correlation between fluid milk consumption and incidence of IDDM in Italy was 0.84 (P < 0.004, Poisson regression analysis). Cheese consumption was not related to IDDM incidence. CONCLUSIONS: The results indicate that there is a relationship, even in a single country, between dairy product consumption and the incidence of IDDM that is confined to fluid milk consumption. Cows' milk may contain a triggering factor for the development of diabetes, but the high incidence of IDDM in Sardinia and in other countries worldwide cannot be explained simply by the quantity of fluid cows' milk consumed. PMID- 7882825 TI - Genes within the major histocompatibility complex predict NIDDM in African American women in Alabama. AB - OBJECTIVE: To test the hypothesis that genes within the major histocompatibility complex (MHC) are associated with gestational diabetes mellitus (GDM) and, subsequently, non-insulin-dependent diabetes mellitus (NIDDM) in African-American women. RESEARCH DESIGN AND METHODS: African-American women who presented with GDM were compared with pregnant African-American control subjects. Following pregnancy, GDM patients were assessed at various intervals of time (median = 6 years) to determine whether they had developed diabetes. RESULTS: GDM patients who required insulin during pregnancy possessed a significantly higher frequency of A33, DR2, DR9, and BF-S phenotypes than control subjects. GDM patients who subsequently developed NIDDM had a significantly higher frequency of B41, DR2, and BF-S and a lower frequency of DR1 and DR6 phenotypes than control subjects. Even after controlling for age and body mass index, B41 and DR2 were independent predictors of developing insulin-requiring GDM and NIDDM in GDM subjects. CONCLUSIONS: These results suggest that either one or more genes within the MHC are involved in the etiology of NIDDM. PMID- 7882826 TI - Physicians' practices in screening for the development of diabetic nephropathy and the use of glycosylated hemoglobin levels. AB - OBJECTIVE: To compare outpatient screening of diabetic patients for nephropathy and measurement of glycosylated hemoglobin (GHb) levels to published American Diabetes Association (ADA) guidelines. RESEARCH DESIGN AND METHODS: We reviewed charts from 157 diabetic patients followed for 27 months at the University of Washington's primary care clinics. The number of screening urinalyses, 24-h urine measurements, and GHb measurements were obtained. From these values, the frequency of screening tests, normalized by patient-year, could be compared with the ADA guidelines. RESULTS: Forty-two percent of the patients received at least one urinalysis, and 5% had 24-h urine measurements. There were 0.48 urinalyses and 0.05 24-h urine measurements per patient-year. Of 14 type I diabetes patients, 5 had a urinalysis and 1 received a 24-h urine measurement. At least one GHb was measured for 85% of patients, and there were 1.66 GHb measurements per patient-year. Only 29% of patients received GHb concentrations as recommended by ADA guidelines. CONCLUSIONS: Diabetic patients at this institution are not screened for nephropathy and do not receive GHb measurements according to the ADA guidelines. Because of recent advancements in the treatment of diabetic nephropathy and the results of the Diabetes Control and Complications Trial (DCCT), further efforts are needed for educating primary care physicians about standards of care of patients with diabetes. PMID- 7882827 TI - Lower prevalence of impaired glucose tolerance and diabetes associated with daily seal oil or salmon consumption among Alaska Natives. AB - OBJECTIVE: To examine the association of seal oil and salmon consumption with impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) among Alaska Natives. RESEARCH DESIGN AND METHODS: Screening was performed on 666 Yup'ik Eskimos and Athabaskan Indians > or = 40 years old in 15 villages. Self-administered questionnaires were used to obtain partial food frequency data. A case was defined as IGT or NIDDM, either newly discovered or known. Newly discovered cases (11 patients with NIDDM and 17 with IGT) were determined by random blood glucose testing followed by a 2-h 75-g oral glucose tolerance test (OGTT) for those with values > or = 6.72 mmol/l or for subjects with unconfirmed histories of glucose intolerance. Known cases included 26 patients with NIDDM and 1 with IGT. Control subjects had random blood glucoses < 6.72 or normal OGTT results. RESULTS: Compared with less-than-daily consumption, both daily seal oil (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.1-0.8) and daily salmon consumption (OR 0.5, CI 0.2-1.1) were associated with a lower prevalence of glucose intolerance, controlling for age, ethnicity, body mass index, and sex. The effects were similar when limited to newly discovered cases: OR 0.3, CI 0.1-1.3 for seal oil and OR 0.4, CI 0.1-1.3 for salmon. Consumption of seal oil at least five times per week was required to reduce risk. CONCLUSIONS: Consumption of seal oil and salmon, high in omega-3 fatty acids, appears to lower the risk of glucose intolerance and is a potentially modifiable risk factor for NIDDM in Alaska Natives. PMID- 7882828 TI - Protein content of the diabetic diet. PMID- 7882829 TI - Standards of care for diabetes. PMID- 7882830 TI - The genetics of NIDDM. An update. PMID- 7882831 TI - Dietary fiber guidelines in the Exchange Lists for Menu Planning. Should they be revised? PMID- 7882832 TI - Stepwise and combination drug therapy for the treatment of NIDDM. PMID- 7882833 TI - Cardiovascular autonomic neuropathy. Where have we been and where are we going? PMID- 7882834 TI - There should be a national American Diabetes Association program for diabetes screening. PMID- 7882836 TI - Lipoprotein(a) levels in type II diabetic patients are not influenced by metabolic control or by microalbuminuria. PMID- 7882835 TI - Osler and his students. The "sweet pea" episode. PMID- 7882837 TI - IDDM and celiac disease. PMID- 7882838 TI - Unproven therapies. American Diabetes Association. PMID- 7882839 TI - Diabetes and managed care. PMID- 7882840 TI - [Diagnosis and treatment of thyroglossal cysts and fistulae (Sistrunck or Schlange?): reflections on 40 cases]. AB - 40 cases of cysts and fistulas of the thyroglossal tract duct offer to the authors occasion to review the rare problems of diagnosis raised by this pediatric pathology. They compare the results of surgery obtained by the classic technic of Sistrunck (1920) versus the Schlange's operation (1893) which remove the cyst with the hyoid bone's body only. The average of age is 17 years. A location of a thyroglossal cyst in the submandibular area was noted during operation. Sistrunck's operation was performed in 21 cases (52.5%) and the Schlange's one in 14 cases (35%) without recurrence. 4 cases (10%) recurrences were noted, all after simple cystectomy. Removal of the hyoid bone's body appear to us as the key of success in the surgery of thyroglossal anomalies. PMID- 7882841 TI - [Neck trauma in civil practice: a 16-year experience]. AB - In spite of their seriousness, neck traumatism still are an unknown pathology. In a 16 years old hospital practice we have recorded 27 cases of neck traumatism. They concern, mainly, male adult. Accidental circumstances deal only with civil practice. The vulnerant agent is white weapon in 63% of the cases either in a suicide or aggression purpose. Because it occurs, mainly, with white weapons, penetrating wounds are more frequent (85%). Exploration cervicotomy has been indicated for 23 patients. But it was effective for only 22 patients. In 83% of cases surgery occurred in the first 48 hours delay. It permitted to find out a 78% score of aero-digestive tracks, and about 22% of vascular injury. We have recorded two death cases. One of them was noticed after surgery. These 27 cases do not, indeed, reflect the reality. Many people who died immediately after their accident may have undergone unseen neck traumatisms. By the same way, numbers of "closed" internal neck traumatisms have been misknown in the hospital. We, thus, suggest a reorganisation of surgical and medical emergencies in Senegal. PMID- 7882842 TI - [An attempt to analyse the recovery mode effects on heart rate and performance in a series of 400 meter flat race]. AB - 22 subjects divided into two groups A and B have to observe respectively passive and active recuperations. The analysis of the results shows that the subjects of Group B present a lower pulse rate at the end of the test. However, their average heart rate is not significantly different form that of the subjects of Group A. Group B is significantly more performant than Group A with regard to the total distance covered (P < 001) and duration (05 > P > 01). PMID- 7882843 TI - [Hygienic and commercial quality of Senegalese frozen shrimp]. AB - 100 samples of shrimps (frozen entire raw shrimps: FERS and frozen peeled raw shrimps: FPRS) collected in one urban factory, were studied to assess their hygienic and commercial quality. In addition to bacteriological analysis, the dosage of residual bisulphite content was carried out. It appeared that: level of aerobic plate was high for FERS: 2.55.10(4)/g and weak for FPRS: 2.45.10(5)/g; level of psychrotophic micro organisms was relatively high for FERS: 1.07.10(4)/g and very weak for FPRS: 0.53.10(4)/g; level of fecal coliform was high for fers: 30.62/g and FPRS: 68.75/g; Staphylococcus aureus and Anaerobic sulphite reducing organisms counts were low; neither salmonella nor Vibrio parahaemolyticus was found; residual bisulphite content is higher than the standard in 10 p.100 of samples. The upholding of the exported level of senegalese shrimps implies and improvement of their hygienic quality. PMID- 7882844 TI - [Colic occlusions: retrospective study of 62 cases]. AB - The profile of colic occlusions has been drawn from sixty two (62) observations made at the Surgical Clinic between 1970 and 1984. The male sex was slightly more affected (3 men for 2 women) with the age of the patients ranging from 19 to 82 years. The clinical sign could be summed up as following: a montrous ballooning of the abdomen which is asymmetrical in 89% of the cases. The occlusions with a stade of shock represented 58% of our observations. The abdomen plain film exhibited the characteristic signs in 89% of the cases. The etiology is dominated by the volvulus of the pelvic colon in 83% of the cases. The essentially surgical treatment has mostly consisted on a resection-anastomosis. Mortality rate was 9.7%. Late consultation of the patients, the shortage of fully equiped medical infrastructure explain the gravity of the affection. PMID- 7882846 TI - [Non-religious prohibitions of meat consumption in Senegal]. AB - 680 persons belonging to all ethnical and religious groups in various regions of Senegal, have been questioned to know types of meat they avoid for non religious beliefs. The results show that: 25% of responses are related to prohibited meat for patronymic names (family names), reason comparable to "totemism". Camel flesh is in this group. 75% of responses deal with prohibitions of consumption connected with various beliefs. So is the case of goat meat avoided by 13% of persons, because it would transmit leprosy or reveal incubating diseases. 14% of persons questioned said that Spiegel lobule of liver must be exclusively consumed by only sons or only daughters. Meat taboos connected with socio-cultural beliefs (totemism, mimetism) have a minor impact on the global consumption of this food. PMID- 7882845 TI - [Dental cavities in the urban, suburban, and rural environment among school children from the region of Dakar]. AB - An epidemiological survey on 2.067 children from 7 to 12 years old in average carried in three urban, suburban and rural school environments, has shown that dental caries prevalence is not yet alarming in the district of Dakar, and that the caries index remain more high in the urban environment than in the rural environment. However face to the urbanization and the industrialization of this region, the modification of the alimentary habits appear to be facilitating factors of the raising of the dental caries prevalence in the coming years if nothing is done. It's why preventive measures have to be taken based over all on dental health education and dental health information in organized structures like school. PMID- 7882847 TI - [Expulsive hemorrhage (report of 2 cases)]. AB - Two cases of expulsive haemorrhage consecutive to an operation of intumescent cataract responsible of major ocular overpressure (60 and 70 mmHg) are reported by the authors. No other risk factor has been found in our patients, one of 45 years old and the other 72 years old. First nor the operative wound suture neither the posterior sclerotomy were stitched, because of the inability to discover the site of choroidal haematoma with quat amount of blood in the operative field. The second reason was the use of an inadequate material of suture (vicryl 9/0). Finally both cases presented were eyes without any light perception. The final phase results in phtysis phenomena. PMID- 7882848 TI - [Genetic variability of growth in sheep grown at the animal husbandry research center of Dahra]. AB - Data on growth performances of 778 Peulpeul and Touabire sheep were collected over five years (1983-1987) in APRC of Dahra. Studied parameters were: birth weight (BBW), one month weight (MBW), weaning weight (WBW) yearling weight (YBW) and growth rate between adjacent stages of growth. BBW, MBW, WBW and YBW are: 3.6 +/- 0.6 kg, 9.5 +/- 1.8 kg; 17.5 +/- 3.5 kg; 30.6 +/- 4.3 kg. Growth rates were 197.0 +/- 51.2 g between birth and one month (MGR), 87.2 +/- 28.1 g, between one month and weaning (WGR) and 50.8 +/- 15.3 g, between weaning and yearling (YGR). Year and season of birth, dam parity, prolificity, sex and race had significant effect on most of the parameters studied. The heritability estimates were 0.50 +/ 0.14 (BBW), 0.52 +/- 0.15 (MBW), 0.71 +/- 0.18 (WBW), 0.44 +/- 0.13 (MGR) and 0.60 +/- 0.16 (WGR). High and positive correlations existed between BBW and the other growth components. PMID- 7882849 TI - [Antihypertensive action of Parkia biglobosa+ (Jacq) Benth seeds in the rat]. AB - Hundred white Wistar rats have been used to evaluate the antihypertensive effects of entire seeds and decorticated, fermented seeds of a soudanian plant, Parkia biglobosa. The arterial blood pressure was measured by using bloody method in anesthizied animals. The Pham Huu Chanh method was used to determine type plant's antihypertensive activity. According to the results obtained, in both preparations, adequate doses decrease arterial blood pressure, diastolic more than systolic, but the effect of fermented seeds was more important than the entire seeds. In the two cases, the decrease in blood pressure is greated in hypertensive than in normotensive subjects, and the hypotension induced was well correlated with a bradycardia. PMID- 7882850 TI - [Tetanus and traditional practices in Dakar (report of 141 cases)]. AB - In this study undertaken in the Infectious Diseases department CHU Fann Dakar, between january 1982 and december 1990 the authors report their observations about 141 cases of tetanus occurred by traditional practices: circumcision, excision, tattooing, scarification, ears piercing. The annual incidence of tetanus occurred by traditional practices was 15.6 cases. It represents 3.6% of all tetanus cases during the study period (n = 3844). The circumcision represents 59.4% (n = 84), the ears piercing 34.4% (n = 48), excision 2.8% (n = 4), scarification 2.1% (n = 3) and tattooing 2 cases. The mortality of tetanus occurred by traditional practices was 8.5%. Health education, information and vaccination against tetanus for all ages according to WHO recommendations will help to eradiquate tetanus in developing countries. PMID- 7882851 TI - [Acidity and microbial flora contaminating Senegalese reconstituted curdled milk produced on small scale]. AB - The present study is carried out to appreciate the acidity, and survey the microbiological quality of reconstituted curdled milk (R.C.M.) obtained on small scale. For his, a total of 100 samples collected from Dakar's sellers were examined. The results show that: pH of R.C.M. is low and very variable: 4.17 +/- 0.30, titrable acidity is high: 152.6 +/- 26.5 degrees D, 5% of samples are contaminated by fecal coliforms and yielded counts of 20 germs/g, 19% of samples are polluted by Staphylococcus aureus to level equal to 10(2) germs/g or higher, yeasts and moulds are present in all samples, salmonella were absent. Saphylococcus aureus survival in curdled milk despite a dysgenesic acidity may be the result of very unhygienic conditions of preparation. Sellers and consumers must be encouraged to respect hygienic rules of preparation. It is the only way to prevent food poisoning. PMID- 7882852 TI - [Senegalese pharmacopoeia: study of acute toxicity and antitussive activity of Calotropis procera AIT (Asclepiadaceae)]. AB - We confirmed the innocuity of different extracts (leaves and stem bark) of Calotropis procera (Asclepiadaceae), a plant widely used in Asian and West African traditional therapy in dermatological and bronchal affections. We proved the against cough activity of the aqueous stem bark extract after administration, per os, upon bronchal irritation by ammoniac on Guinea Pig. PMID- 7882853 TI - [Urinary bacteriology in the elderly in the tropical zone: results of 5 years of activities at the CHU of Fann in Dakar]. AB - The authors report a retrospective account on 5 years (1987-1991) studied on 300 specimen of urine, coming from subjects aged 65 or more and having been submitted to bacteriologic examination in Dakar, Senegal (microscopic examination, counting, isolation, identification of bacteria, antibiotic tests). On the whole, 8150 samples of urine were recorded during the same period in the Laboratory of Bacteriology (CHU de Fann). The results obtained show a particular exposure of the old subjects to urinary tract infection (37%, against 23% in subjects aged less 65 years). The isolation of bacteria was not attached to sex. E. coli and Klebsiella sp. are the most frequently isolated in urine. The most efficacy antibiotics on these agents are the Cepholosporins, the Aminosids, Nitroxolin and Oxolonic Acid. PMID- 7882854 TI - [Choleretic effects of Cassia alata Linn in the rat]. AB - Fifty rats weighing average 200 g were used to study choleretic activity of Cassia alata LINN extract. Bile was collected according to acute biliarly fistula technic on animals anesthetized with 1.5g/kg of ethyle carbamate (Urethane ND). After determination of the minimal active dose (15 mg/kg) and lethal dose (100mg/kg) of the extract, rats were allowed in 5 groups of 10 each one: one reference group, one group receiving 15 mg/kg of Hydroxycyclohexenyl-butyrate (Hebecol ND) a synthetic choleretic, and 3 groups receiving respectively 15 mg/kg, 30 mg/kg and 60 mg/kg of Cassia alata extract. According to results obtained, choleretic activity of Cassia alata at 15 mg/kg is better than the Hebucol ND ones. But at elevated doses, the plant tend to inhibit bile secretion. PMID- 7882855 TI - [Types of meat preferred by Senegalese people]. AB - 680 senegaleses consumers have been surveyed in order to know the types of meat they prefer and the criteria of their choice. Responses collected reveal that: they like better mutton (95% of responses) because it is tender, tasty and sacred; entire male meat is preferred (74% of responses) to castrated or female meat (14 and 2%) from more habit, or because it is a symbol of strength; they like better meat from young animal; their favourite cuts are cutlets which are appropriate to grilled meat; imported frozen meat are rejected by many consumers (86.5%). They think that frozen meat is less whole some and less conformable to islamic rules than local fresh meat. These results must be considered in order to satisfy the consumers demand. PMID- 7882856 TI - [Fluconazole in oro-pharyngeal candidiasis in retroviral infection (experience in Dakar)]. AB - Oral candidiasis is a frequent opportunistic infection in AIDS patients. High risk of dissemination and frequent relapses are common. The autors in Dakar at the Infectious Diseases Department Fann Hospital conduct an open non randomized trial with Fluconazole for the treatment of oral candidiasis in HIV seropositive patients. They find a clinical efficacy of 84.14% a biological efficacy of 63.3% and a good excellent tolerance (100%). But, the high price of this product limits its utilisation in developing countries. PMID- 7882857 TI - [Pterygo-cavernous thrombophlebitis and temporo-mandibular ankylosis in dental infections]. AB - The authors report the complications of a case of cellulitis from dental origin. A cavernous sinus thrombophlebitis and a temporo-mandibular ankylosis succeed, pointing on the importance of a precocious treatment of dental phlegmons, in order to prevent occurrence of local or regional complications. PMID- 7882858 TI - [Antibiotic sensitivity of germs isolated from cellulitis of dental origin in Senegal (results of a survey of 49 cases)]. AB - Irregular results sometimes found during antibiotic treatment of perimaxillar cellulitis, conducted the authors to study bacteriology of these infections from dental origin. This study confirmed the aero and anerobic polymicrobism of these cellulitis. Antibiograms realised in 49 cases showed occurrence of streptococcal and anaerobic germs resistance to antibiotics usually prescribed. A nearly constant success of other antibiotics allowed the authors to define a first intention antibiotherapy for the treatment of these infections. PMID- 7882859 TI - [Ocular manifestations of AIDS in Dakar]. AB - In this prospective study undertaken between november 1989 and december 1991, the authors report their observations of ocular lesions seen in a cohort of 67 AIDS patients hospitalised in the Infectious Diseases department CHU Fann Dakar. Ocular lesions were discovered in 52.23%. These lesions were observed in both HIV 1 and HIV-2 positive patients, however they were much more common in the former group (77.14%). Retinal pathology was by far the most frequently observed (63%) and yet classic retinis was not discovered in our series. We feel that the ophtalmologist should play a key role in the routine care of AIDS patients especially in surveillance of retinal changes. PMID- 7882860 TI - Applying system-based family models: what to look for in assessing critical care families. PMID- 7882861 TI - Radiofrequency catheter ablation for Wolff-Parkinson White syndrome. Part 2: Preventing complications. AB - To significantly reduce the morbidity, mortality and life long dependence on antiarrhythmic medications, radiofrequency catheter ablation has emerged as the treatment of choice for patients with preexcitation disorders occurring with the Wolff-Parkinson-White (WPW) syndrome. Radiofrequency ablation is usually highly successful (> 95%), with a near zero mortality and low morbidity. This article, the last in a series of two, focuses on preventing complications for patients undergoing this procedure. PMID- 7882862 TI - Families are not visitors in the critical care unit. PMID- 7882863 TI - Promoting ventilator independence: a grounded theory perspective. AB - This qualitative study describes a distinctive nursing perspective on the process of ventilator weaning that is not well documented in current literature. The investigators used interviews with expert critical care nurses to reveal the knowledge, judgments, and actions used by nurses to promote ventilator independence. The authors identify a nursing diagnosis and three themes that offer a theoretical framework for ventilator weaning and suggest nursing interventions that promote successful ventilator weaning. PMID- 7882864 TI - Minitracheostomy: an alternative to "blind" endotracheal suctioning. AB - The critical care nurse is frequently challenged to clear respiratory secretions for patients with thick, copious mucous and a weak cough. The traditional interventions nurses use are chest physiotherapy, incentive spirometry, and "blind" endotracheal suctioning to facilitate the removal of secretions, but these are sometimes ineffective and cause complications. Nurses who identify patients needing a more effective way to remove secretions can request consideration of a new method, suctioning through a minitracheostomy. PMID- 7882865 TI - Selecting a model to guide family assessment. AB - Theoretical models can help critical care nurses deliver planned and systematic care to families in a time-efficient manner. This article describes three family theoretical models: structural-functional, family systems, and family stress. PMID- 7882867 TI - Crossword puzzles: a teaching strategy for critical care nursing. AB - Crossword puzzles are an effective teaching and learning tool in critical care education. They are especially effective for teaching details that need to be memorized. The positive outcomes are well worth the creative efforts of the educator. PMID- 7882866 TI - Patient-family conflicting issues. Part 1: The case. Part 2: Case analysis. AB - This article describes an ethical case when the patient's wishes and that of her spouse disagreed and the ethical issues which were involved. Although the patient clearly has the right of choice on treatment, her own choices became ambivalent as she recognized her husbands need for her to fight on. PMID- 7882868 TI - Results of the NIDA treatment demonstration grants' cocaine workgroup: characteristics of cocaine users and HIV risk behaviors. AB - This journal issue includes seven articles (six plus this introduction) from the "cocaine workgroup" of the National Institute on Drug Abuse (NIDA) treatment demonstration grants. In this introduction, results of the first attempts to compare data from seven disparate demonstration grant sites are summarized: Overall, rates of recent cocaine use were high in all locations, injection drug use was common, age of first drug use was between 14 and 17 years with age of first cocaine use between 20 and 25 years, arrests were common at all sites especially among cocaine injectors, and polydrug use was the norm. Interestingly, both gender and ethnic status were significantly associated with polydrug use and marijuana use among the cocaine users. These results indicated that it is possible to define variables precisely for analysis across sites and laid the groundwork for the next set of analyses in which the common theme of human immunodeficiency virus (HIV) risk behaviors among cocaine abusers was agreed upon. This next set of analyses are included in the following six papers. Overall, these reports confirm recent data about the association of cocaine use with HIV risk behaviors. They extend considerably the literature on the association of cocaine with HIV risk behaviors, and the report from New York in which therapeutic community treatment was shown to be feasible and possibly useful to methadone clients represents an interesting and new finding. In conclusion, cross-site collaborations can take different forms and this collection of papers represents one successful approach. PMID- 7882870 TI - HIV risks, gender, and cocaine use among opiate users. AB - HIV risks involving injection and sex behaviors were analyzed in relation to cocaine use and gender among 487 opiate-dependent clients in methadone treatment. Those who also used cocaine were at greater risk than non-cocaine users on HIV risky injection variables. Females were at more risk than males on the HIV risky sex behaviors involving unprotected sex in exchange for money or drugs and with injection users. There were interactions between cocaine use and gender, however, in relation to frequency of injecting with dirty works and sharing dirty works with strangers, as well as having unprotected sex for money or drugs, with injection users, and while intoxicated. HIV risks increased as a direct function of cocaine usage level among males, but not among females; instead, low-to intermediate levels of cocaine use by females was associated with high-risk behaviors. Implications for HIV risk reduction interventions in drug treatment programs are discussed. PMID- 7882869 TI - Cocaine and crack use and HIV risk behaviors among high-risk methadone maintenance clients. AB - A discriminant function analysis was performed with data from 409 high-risk heroin addicts at intake into a methadone maintenance treatment program to determine the characteristics of cocaine users. Cocaine users presented a higher risk profile for human immunodeficiency virus (HIV), engaged in a wider variety of criminal activities, were more likely to be African-American, reported more alcohol use, and showed more signs of psychological disturbance. A second discriminant function analysis determined that crack smokers differed from non crack cocaine users in ethnicity, alcohol use, criminal activity, needle use, and marital status. Heroin addicts who use cocaine, in particular crack, represent a sub-group at higher risk and in need of targeted treatment planning and monitoring. PMID- 7882871 TI - Cocaine use and HIV risk behavior in methadone maintenance patients. AB - This study examined sexual and drug use behavior in 247 methadone maintenance patients, to explore the association of cocaine use with human immunodeficiency virus (HIV) risk behavior. In univariate analyses, cocaine use was positively associated with any drug injection, number of injections, and sexual intercourse without condoms. These relationships remained significant after controlling for other drug use and demographic factors. Heroin use also contributed to injection related risk. We conclude that cocaine use represents a continued source of risk for exposure to HIV in this population, and that more aggressive efforts are warranted to reduce illicit drug use, particularly of heroin and cocaine, in methadone patients. PMID- 7882872 TI - Is antisocial personality disorder associated with increased HIV risk behaviors in cocaine users? AB - Previous reports have shown antisocial personality disorder (ASPD) to be strongly associated with injection equipment sharing and increased rates of human immunodeficiency virus (HIV) infection in a sample of heroin injectors. Another report has shown ASPD to be associated with injection drug use, needle sharing, sexual promiscuity, and prostitution in a sample of methadone maintenance clients. The current study extends this work by examining the relationship of ASPD and human immunodeficiency virus (HIV) risk behaviors in a sample of cocaine users (48% out of treatment and 52% just entering treatment). Associations were tested for sexually risky behaviors in addition to injection behaviors. The principle finding of this study is that ASPD was shown to be associated with increased rates of injection drug use and sharing syringes, with earlier age of onset of injection drug use, with certain venereal diseases, and with a variety of HIV risk sexual behaviors. When men and women were tested separately, the pattern of association of risky behaviors with ASPD varied considerably. Overall, this work confirms that psychiatric status, especially the presence of ASPD, may have to be considered in evaluating the results of HIV risk-reduction interventions. PMID- 7882873 TI - Therapeutic community methods in methadone maintenance (Passages): an open clinical trial. AB - A non-random open clinical trial was conducted to determine whether a day treatment program based on modified therapeutic community (TC) methods (Passages) produced better treatment outcomes for heroin addicts than did standard methadone maintenance therapy. Altogether, 327 methadone clients at two clinic sites were studied: 115 Passages members, and 212 comparison subjects. Compared to non Passages clients, clients who voluntarily joined and remained in Passages for at least 6 months exhibited significantly larger reductions in cocaine use, heroin use, needle use, criminal activity, and psychological dysfunction. The present findings suggest that TC-oriented enhanced day-treatment can help methadone clients recover from drug abuse and adopt a prosocial lifestyle. PMID- 7882874 TI - Patterns and covariates of alcohol drinking among high school students in 10 towns in Italy: a cross-sectional study. AB - A self-report questionnaire on alcohol and tobacco use was administered anonymously to 5221 high-school students in grade 9 (aged 14-15) and to 4154 students in grade 13 (aged 18-19) in 10 Italian towns. Alcohol consumption was greater among males than females and among 13th graders with respect to 9th graders. Students who drank alcoholic beverages every day were, in males and females, respectively, 22.5% and 9.0% among 9th grade and 31.3% and 10.0% among 13th grade students; those who drank 7 or more alcohol units a week were 26.8% and 11.1% among 9th grade and 42.7% and 13.9% among 13th grade students; finally, those who felt drunk at least once in the last 12 months were 19.8% and 13.9% among 9th grade and 41.4% and 19.0% among 13th grade students. Both alcohol consumption and frequency of drunkenness were found to be associated with both experimental and regular cigarette smoking and with psychoactive drug consumption, but not with socio-economic, cultural and demographic factors. Two main distinct drinking patterns were found among Italian adolescents: on the one hand, the daily drinking of moderate amount of wine with meals, together with parents, which was more common among males than females, as in other 'Latin' countries; and on the other hand, the occasional intake of alcoholic beverages in excess, especially beer and spirits, out of the family but together with peers. PMID- 7882875 TI - Cocaine use and risky injection and sexual behaviors. AB - The association between cocaine use (crack and injection cocaine) and risky behaviors for human immunodeficiency virus (HIV) infection was investigated among participants in a multi-site study at drug treatment and non-drug treatment sites in Worcester, Massachusetts. Cocaine use was more prevalent among young, African American men. Compared to heroin injectors cocaine injectors had higher risk injection and sexual behaviors. Among non-injectors, crack users were more likely to have multiple partners and receive money or drugs for sex. Cocaine use, either injected or smoked as crack, should be considered a high risk behavior for HIV infection. PMID- 7882876 TI - Drinking and unemployment: contrasting patterns among men and women. AB - Research on unemployment has paid only little attention to drinking and drinking problems. From the 1970s onwards the association of drinking and unemployment has come under systematic study. Contrasting tendencies emerge from this research. This paper distinguishes three instances of drinking and drinking problems and examines their association with employment status, i.e., (i) frequency of drinking, (ii) frequency of intoxication, and (iii) frequency of health problems due to drinking. A panel survey was conducted in 1983-1984, consisting of a sample of Finnish men and women, originally jobseekers in industry. Prevalence data and results of logistic regression analyses on the association of the three instances of drinking and drinking problems with employment status are presented. The frequency of drinking was unassociated with employment status for men and women at either of the two measurement points. Neither did the frequency of intoxication show any clear association with employment status. In contrast, the frequency of health problems due to drinking was associated in a statistically significant way with unemployment among men. Among women the association was rather the opposite, but it was not statistically significant. The paper concludes that it is important to distinguish between overall drinking and drinking problems, and between the determinants of male and female drinking problems. It is likely that selective processes at the labour market as well as social causation during unemployment lie behind the observed association of male unemployment and drinking problems. PMID- 7882877 TI - Illegal drug taking and driving: patterns of drug taking among Spanish drivers. AB - This study investigated patterns of illegal drug taking among Spanish drivers. The study was conducted in the fall of 1993 on 1500 drivers aged over 16, who properly completed and returned the questionnaires. The statistical SAS package was used. Among those surveyed, 23.5% had taken illegal drugs within their lifetime, 6.1% in the past year, 4.2% in the past month and 3.1% in the past week. Cannabis was the drug most frequently taking drug within lifetime (17.3%), the past year (3.4%), the past month (2.7%) or the past week (2.1%). Of those surveyed, 3% had driven after taking illegal drugs in the last year before the survey, and had been stopped during road checks (P < 0.001) and involved in road accidents (P < 0.0001) more often than those who had not driven under the influence of drugs. The study shows that driving under the influence of illegal drugs is somewhat frequent in Spain. PMID- 7882878 TI - Mixed adenoma of the middle ear. PMID- 7882879 TI - Post-hemorrhagic vocal fold polyps. PMID- 7882880 TI - Endoscopic view of Thornwaldt cyst of the nasopharynx. PMID- 7882881 TI - Hearing improvement following removal of acoustic neuroma with preoperative sudden deafness. AB - We report three cases of small intracanalicular acoustic tumor with sudden hearing loss (SHL). The tumors were totally removed through the middle cranial fossa approach, preserving both the facial and cochlear nerves between one and four months after the onset of deafness. From one to three months postoperatively hearing has improved significantly. Hearing improvement in acoustic tumor surgery is a new aspect to be studied more in the future. Although the data are insufficient to draw broad conclusions, surgical removal of small acoustic tumors is rational to improve hearing, reduce or eliminate tinnitus and prevent recurrent attacks of deafness or vertigo. Factors relevant to postoperative hearing improvement are considered. PMID- 7882882 TI - Cephalosporin antibiotics. AB - The last three decades have seen the emergence of a cornucopia of antimicrobials in the cephalosporin class. This becomes even more apparent when one realizes that over 60 pages of the 1993 AHFS drug information text is dedicated to the cephalosporin class. Due to similarities in nomenclature and the proliferation of available agents, the clinician is constantly challenged by this confusing array of antimicrobials. The intent of this manuscript will be to distill the volumes of information available on cephalosporins into a more manageable format and close with a summary of the most clinically important cephalosporin antimicrobials. PMID- 7882883 TI - Stuttering induced by theophylline. AB - We retrospectively evaluated three fluent asthmatic children who developed speech dysfluency following administration of theophylline. The dysfluency ceased in all three, following discontinuation of the medication. The medication was re instituted in two patients, prompting return of dysfluency. It is unknown whether the patients had characteristics of "acquired stuttering" or "developmental stuttering." We urge appropriate testing should this complication again occur. This might then provide pharmacologic information regarding stuttering. PMID- 7882884 TI - The relationship between vasopressin and endolymphatic hydrops in the guinea pig. AB - Clinical studies have shown that plasma vasopressin level is significantly elevated in patients with Meniere's disease. Other reports indicated that histamine induced a very quick and high elevation of vasopressin level and caused nystagmus in experimentally produced endolymphatic hydrops. We became interested in further investigating the details of this relationship by studying the effect of experimental endolymphatic hydrops and histamine upon plasma vasopressin level in the guinea pig. The results are as follows: 1) Histamine increased the plasma vasopressin level in normal guinea pigs. 2) There was no statistically significant difference in the plasma vasopressin level between the hydrops model and normal guinea pigs. 3) Histamine increased the plasma vasopressin level more in the hydrops model group than in normals. 4) Plasma vasopressin level was elevated in the vertiginous model caused by inner ear anesthesia. Our results support those of clinical investigators who reported that the plasma vasopressin level was elevated more in the Meniere's disease group than any other equilibrium disorder group. It is possible that vasopressin is in someway involved in the development of endolymphatic hydrops. PMID- 7882885 TI - Endoscopic approach to the diagnosis of fibrous dysplasia. PMID- 7882886 TI - Should oral steroids be the primary treatment for allergic fungal sinusitis? AB - A case of Allergic Fungal Sinusitis successfully controlled with oral corticosteroids followed by endoscopic sinus surgery is presented. The clinical diagnosis of AFS is emphasized. Endoscopic sinus surgery is preferable to open sinus techniques since the underlying mucosal disease is reversible. A prospective study is needed to determine the most appropriate treatment for this unique clinical disorder. PMID- 7882887 TI - To do or not to do the conjunctival approach lower eyelid blepharoplasty. PMID- 7882888 TI - Nerve compound action potentials analysed with the simultaneously measured single fibre action potentials in humans. AB - 1. Compound action potentials (APs) and single fibre APs were recorded with two pairs of wire electrodes from an S5 root from a paraplegic patient during surgery. 2. Frequency distribution histograms of single nerve fibre conduction velocities were constructed and nerve fibre group conduction velocities compared with the conduction velocities of the peaks of the compound APs. By increasing the strength of the stimulation, the peaks in the compound AP could be identified, and the threshold order of efferent nerve fibre groups determined. Using additional literature data, it is likely that the primary spindle afferents have the lowest threshold due to electrical nerve root stimulation followed by the alpha 1-motoneurons (FF), the secondary muscle spindle afferents, the alpha 2 motoneurons (FR), the alpha 3-motoneurons (S), the gamma beta, gamma 1 (dynamic), gamma 21 (static), gamma 22 (static), and the parasympathetic motoneurons. 3. In first approximations, the Ap duration increases in the same way as the AP amplitude decreases with decreasing conduction velocity, and the area between the average single fibre AP curve and the base-line is the same for all single fibre APs with an average same distance to the recording electrodes in the root cross section. By comparing the mean area of a single fibre AP with the areas of the peaks of the compound APs, it was found that 230 single fibre APs contributed to the compound AP. In the secondary spindle afferent fibre and alpha 2-motoneurons groups 53 fibres were stimulated (23%). The alpha 3-motoneuron peak and the afferents in the same velocity range contained 101 fibres (44%), the gamma beta peak contained 9 fibres (4%), the gamma 1 32 (14%), the gamma 21 23 (10%) and the gamma 22 12 (5%) fibres. Additionally two primary spindle afferents and two alpha 1-motoneurons most likely contributed to the compound AP. Since the large peaks in the compound APs did not change their area with increasing stimulation, most likely all muscle spindle afferents and alpha-motoneurons were activated to contribute to the compound AP. 4. Transfer functions of nerves and the stimulation with natural impulse patterns of the adequate afferents to spinal oscillators with respect to continence in paraplegia are discussed. PMID- 7882889 TI - Parasympathetic autonomic neuropathy in diabetes mellitus: the heart is denervated more often than the pupil. AB - In one hundred subjects with diabetes mellitus assessed by the techniques of power spectral analysis of heart rate variability and heart rate variability during deep breathing, parasympathetic (vagal) cardiac denervation was shown to occur approximately twice as commonly as parasympathetic pupillary denervation measured by the maximal velocity of pupillary constriction. The pupillary dysfunction was detectable only when both tests of cardiac innervation were abnormal as well. No correlation was found between any of the autonomic measures and duration of known diabetes or degree of metabolic control. PMID- 7882890 TI - Carpal tunnel syndrome in Mucopolysaccharidoses. A report of four cases in child. AB - Carpal tunnel syndrome (CTS) is very uncommon in childhood. Sixty-five cases are reported in the literature, principally due to metabolic diseases. In Mucopolysaccharidoses, prospective studies (Wraith and Alani, 1990) found a bilateral CTS in about 90%. We report four cases of Mucopolysaccharidoses, diagnosed on clinical and biological data (two cases of Hurler disease, and two cases of Hunter disease), in children aged less than five years. Each child had claw hands, without thenar atrophy. Median nerve conduction studies and electromyography confirm the CTS. Motor and sensory nerve conductions are normal in other nerves. Concentric needle studies show in two cases, on abductor pollicis brevis, spontaneous activities as repetitive discharges, fasciculations and multiplets. Median nerve stimulations reveal responses with late potentials during 70 ms due to reinnervation. The physiopathology of those carpal tunnel syndromes is discussed. PMID- 7882891 TI - Excitability of the soleus motoneuron pool revealed by the developmental slope of the H-reflex as reflex gain. AB - The excitability of a motoneuron (MN) pool was evaluated by the developmental slope of H-reflexes (Hslp) evoked at a range of a stimulus intensity less than the threshold of an M-response. The Hslp has been regarded as the "reflex gain", which is the changing rate in MN excitability as a function of the increase of Ia input to an MN pool. In a comparison of two parameters used in the H-reflex technique, such as the ratio of the maximal H-reflex to the maximal M-response and the ratio of the threshold of an H-reflex to that of an M-response, the Hslp was predicted to be a reasonable parameter to evaluate motoneuronal excitability, because the Hslp is free from the effect of any collision between the H-reflex discharge and the antidromic volley drived from the occurrence of an M-response within the alpha-efferents, and the Hslp can estimate the recruitment properties of a whole MN pool. The Hslp was alleviated during dorsi-flexion and steepened during plantar-flexion, according to the inhibitory or facilitatory synaptic modifications onto soleus MNs. The developmental slope of an M-response (Mslp), which shows the recruitment property of axons of soleus MNs, was alleviated especially in plantar-flexion. In order to exclude the peripheral neuromuscular factors in evaluating substantial MN excitability, the Hslp/Mslp is proposed as a more effective parameter than the Hslp. PMID- 7882892 TI - Percutaneous sciatic somatosensory evoked potential. A comparison to the transcutaneous response. AB - Cerebral and spinal evoked potentials were recorded in response to percutaneous stimulation of the sciatic nerve at the inferior gluteal crease. To justify the invasiveness of the procedure, a comparison was made to transcutaneous stimulation of the inferior gluteal nerve at the same level. PMID- 7882893 TI - Some differences of the electromyographic erector spinae activity between normal subjects and low back pain patients during the generation of isometric trunk torque. AB - A method of evaluation of the isometric trunk extension effort and integrated electromyographic activity of the low back muscles during straight position under goniometric control was used. In order to evaluate the paravertebral muscle activity, two pairs of bipolar surface EMG electrodes have been attached bilaterally over the erector spinae muscles at a lateral distance of 3 cm at the level of L3 spinal processus. 40 patients with low back pain and 40 normals were involved to participate in this study. EMG activity and strength was higher in normals than in patients. However, this distinction was statistical significant in strength, and nonsignificant in EMG activity. Patients showed relatively higher, asymmetric and more expressive in the painful side integrated electromyographic activity under maximal and submaximal contraction. Strength/EMS relationship was close to linear in normals, whereas in patients this proportionality was nonlinear. Therefore in patients a smaller tension correlated with relatively higher muscle activity. PMID- 7882894 TI - Turn analysis of the EMG: the amplitude definition of a turn. AB - Traditionally and arbitrarily an EMG interference signal (EMGIP) "turn" is defined as any 100 microV signal amplitude change. There have not been planned studies challenging this definition. Here, EMGIPs, recorded by coaxial needle electrodes, in MVC, from biceps brachii muscles of 143 subjects, in three diagnostic groups (Normals, Neuropathics, Myopathics), were analyzed in search of the effects of different turn definition amplitude values (TDEF) on the EMGIP number of turns, average turn amplitude, their ratio, and on the cumulative turn amplitude. This study shows significant differences between the diagnostic groups. It shows that TDEF has significant effect on the number of turns, the average turn amplitude, their ratio, the cumulative amplitude, and that certain TDEFs are significantly better than others in the diagnosis of neuromuscular diseases. Also, it shows that the number of turns and the turns to average amplitude ratio are better measurements than the average turn amplitude and than the cumulative turn amplitude in showing differences between the EMGIPs of the various diagnostic-groups. As such, some of the smaller TDEFs are significantly better diagnostically than the traditional 100 microV value. Also, it shows that better discrimination between the diagnostic-groups may be achieved by applying more than one TDEF value onto the same data. This study leaves the question of the best TDEF or best TDEF sets open for further research in similar and in different paradigms and technical settings. PMID- 7882895 TI - Needle electromyographic evaluation of the diaphragm. AB - Needle electromyography of the diaphragm is a useful tool in diagnosis and prognosis of patients with diaphragmatic dysfunction. Spontaneous activity, polyphasic motor units and decreased recruitment can be found in phrenic nerve and spinal cord injury. We describe a safe technique for studying the diaphragm using needle electrodes. PMID- 7882896 TI - Membrane iodothyronine transporters. Part I: Review of physiology. PMID- 7882897 TI - Thyroxine secretion rates during pregnancy in the rat. AB - Thyroxine secretion rates (TSR) at various stages of pregnancy in rats were measured by the radiothyroxine pool-turnover method. Groups of rats included normal controls (non-pregnant), days 5, 10, 20, and 22 of pregnancy and near term (within 24 hours prior to parturition if past 22 days of pregnancy). Each animal had blood samples taken just prior to injection of 10 microCi L-thyroxine (L-T4) 131I and at 12, 24, 36, and 48 hours afterwards. Determinations of thyroxine iodine (T4-I), volume of distribution (VD), fractional turnover rate (K), and L T4 pool size were made from these samples. TSR was calculated as the product of (1.54) (T4-I) (VD) (K). An increase in TSR occurred near term, 3.65 micrograms L T4/day compared to 1.23 micrograms L-T4/day in the controls, was primarily due to an increase in VD from 33.9 ml in the controls to 90.0 ml near term. A rapid increase in TSR to 3.65 micrograms L-T4/day just prior to term was postulated to be due to a stimulatory action of relaxin in the presence of estrogen upon L-T4 utilization. The mechanism of the increase in TSR in pregnant rats is probably due to the effect of several hormonal changes in maternal tissues throughout pregnancy and to adaptation of the pregnant animals to higher metabolic needs of the rapid developing fetuses. PMID- 7882898 TI - Inhibition of luteal steroidogenesis by two LHRH antagonists (Nal-Glu and Nal-Arg antagonists) in the pregnant rat. AB - We have examined the effect of two LHRH antagonists (Nal-Glu and Nal-Arg antagonists) on the basal progesterone (P4), pregnenolone (P5) and 20 alpha dihydroprogesterone (20 alpha-DHP) production by luteal cells obtained from day 8 pregnant rats. A dose of 0.1 mmol/l of Nal-Glu or Nal-Arg attenuated basal P4 production by luteal cells after 12, 24 or 48 h of incubation. P5, a precursor for P4 synthesis was also reduced by both doses of Nal-Glu or Nal-Arg (0.1 mmol or 0.1 mumol/l) after 24 h of incubation. A period of 12 h was not sufficient to inhibit P5 production by luteal cells incubated with both doses of Nal-Glu or with the lower dose of Nal-Arg. The higher dose of Nal-Glu and Nal-Arg remained effective in attenuating P5 production by luteal cells after 48 h of incubation. We measured the production of a metabolite of P4, i.e., 20 alpha-DHP to assess whether this suppression in P4 production is due to an enhancement in the P4 metabolism by increasing the activity of 20 alpha-hydroxydehydrogenase. However, instead, we observed (i) a decrease in the production of 20 alpha-DHP by the higher dose of Nal-Glu and Nal-Arg after 12, 24 or 48 h of incubation and (ii) a decrease or no change in the production of 20 alpha-DHP by the lower dose of Nal Glu or Nal-Arg at all time periods of incubation. Based on these observations we conclude that LHRH antagonists exert a direct effect on the corpus luteum and suppress luteal steroidogenesis. This suppression in luteal steroidogenesis could be due to a decrease in the activity of any one of these enzymes of the steroidogenic pathway, viz., cholesterol side chain cleavage (P450scc), a rate limiting enzyme involved in the synthesis of P5 from cholesterol, or 3 beta hydroxysteroid dehydrogenase (3 beta-HSD), which catalyzes the oxidation of P5 to P4 or due to a decrease in activity of both enzymes. PMID- 7882900 TI - The effect of platelet activating factor antagonist (BN 52021) on pregnancy duration and collagen content in the pregnant rat uterus and cervix. AB - In order to study the role of Platelet Activating Factor (PAF) in the mechanism of parturition and connective tissue metabolism in the pregnant rat uterus, we investigated the influence of the Platelet Activating Factor Receptor Antagonist (BN 52021) on gestation duration and collagen concentration in pregnant rat uterus and cervix at term. Total and soluble collagen as well as dry tissue/wet tissue ratio were measured in the BN 52021 treated group (n = 9) and in the control group (n = 13). Gestation duration was evaluated in a group receiving BN 52021 (n = 10) and in a control group (n = 19) receiving pure solvent. There were no significant differences in water content. The total and soluble collagen concentration was also similar to the control in both the uterus and the cervix. The only significant difference was observed in the soluble collagen/total collagen ratio in the uterus. BN 52021 administration did not alter the gestational period. Basing on this experiment we suggest that not all the phospholipid metabolites activated by phospholipase A2 significantly influence the duration of pregnancy and connective tissue metabolism in the pregnant rat uterus. PMID- 7882899 TI - Differential effect of estrogen on the production of cyclin B1, cdc2 p34 and c fos protein in rat uterus. AB - The uterine content of c-fos protein, cyclin B1 (cell cycle protein) and cdc2 p34(cyclin-dependent kinase) in immature and mature rats was determined using the enhanced chemiluminescence(ECL) western blot method. Cyclin B1 was found predominantly in immature rat uterus and cdc2 p34 only in mature rat uterus. Several isoforms of c-fos oncogene protein were present in both mature and immature rat uteri. An additional immunoreactive c-fos protein with an estimated molecular weight of 28 kDa was found in mature rat uterus and was missing in immature uterus. Uteri from ovariectomized rats treated with estrogen and/or ICI 182,780, an antiestrogen, were analyzed by ECL western blot. cdc2 p34 and the c fos 28 kDa protein were found in estradiol-treated rat uteri and were not detected in uteri of control and ICI 182,780-treated animals; whereas Cyclin B1 was absent in uteri from control and estradiol-treated ovariectomized animals. ICI 182,780 administered to estradiol-treated ovariectomized rats blocked the induction of cdc2 p34 and the c-fos 28 kDa protein in the uterus. The present results show that the production of the cell cycle factors, cyclin B1, cdc2 p34 and c-fos, during rat uterine growth are under different regulatory controls. cdc2 p34 and c-fos 28 kDa protein are under the control of estradiol; whereas cyclin B1 and the majority of the immunoreactive isoforms of c-fos are not influenced by this hormone. PMID- 7882901 TI - Prolactin-immune interactions in carcinogen-induced rat mammary tumors. AB - Because many mammary tumors are prolactin (PRL) dependent, tumor-bearing animals are immunocompromised, and PRL directly affects the immune system, we examined the endocrine and immune systems of rats initiated with nitrosomethylurea (NMU) to cause mammary tumors. We tested: a) PRL cells in the pituitary; b) pituitary PRL as detected by radioimmunoassay (RIA), Nb2 bioassay, and induction of interleukin-2 receptors on splenocytes; c) induction of IL-2R on lymphocytes in response to a standard PRL; d) CD phenotype of the splenocytes and tumor infiltrating lymphocytes. We found that 80% of all NMU-treated animals developed mammary tumors 10 to 13 weeks post-injection. PRL cell number, size, and granule content were unaffected. When tested by RIA or by the Nb2 bioassay, there appeared to be approximately 50% less PRL secreted (2 weeks post-injection) by cells of the NMU-treated than the vehicle-treated animals. However, when tested by IL-2R assay, PRL cells of NMU-treated animals secreted 50% more activity. Splenocytes from the treated animals, 2-6 weeks post-injection, expressed fewer IL-2R in response to standard PRL. NMU treatment (12 wks post-injection) increased the numbers of T-cytotoxic cells by 49%, had no effect on T-helpers, and increased the number of IL-2R positive splenocytes by 81%. Our interpretation is that NMU treatment interferes with the feedback of lymphokines on the pituitary with a decrease in the form of PRL detected by the RIA and Nb2 assays and an increase in the form which activates splenocytes, and thus changes the composition and function of the immune system. PMID- 7882902 TI - Macrophage inflammatory proteins: biology and role in pulmonary inflammation. AB - Macrophage inflammatory proteins 1 alpha and beta (MIP-1 alpha and beta) and macrophage inflammatory protein 2 (MIP-2) are approximately 6-8 kd, heparin binding proteins that exhibit a number of inflammatory and immunoregulatory activities. The MIP proteins are members of a superfamily of cytokines called chemokines, many of which have been shown to possess chemotactic activity for inflammatory and immune effector cells. While MIPs were originally identified as secretory products of endotoxin-stimulated mouse macrophages, these chemokines are produced by a variety of cell types including neutrophils, fibroblasts, and epithelial cells. In addition, proteins with a high degree of structural and functional homology to murine MIP-1 alpha and beta and MIP-2 have been identified in other species including humans. MIP-1 alpha and beta are chemotactic for monocytes and lymphocytes and MIP-2 is a potent chemotactic factor for neutrophils. MIPs likely also play a role in regulating hematopoiesis and stimulating production of other inflammatory mediators such as IL-1, TNF alpha, and histamine. Studies using animal models of lung injury and inflammation have implicated MIPs as important mediators of lung defense. Increased MIP expression has been observed in models of bacterial sepsis, silicosis, and oxidant-induced lung injury. Studies in humans indicate MIP-1 alpha contributes to the inflammatory cell response associated with sarcoidosis and idiopathic pulmonary fibrosis. Given the bioactivities of MIP-1 alpha and beta and MIP-2 and the recent studies demonstrating their association with lung inflammation, it is likely these chemokines play a significant role in respiratory tract defenses and may contribute to the pathogenesis of inflammatory lung disease. PMID- 7882903 TI - Alveolar epithelial composition and architecture of the late fetal pulmonary acinus: an immunocytochemical and morphometric study in a rat model of pulmonary hypoplasia and congenital diaphragmatic hernia. AB - The aim of the present study was to compare the architecture and alveolar epithelial cell composition of the pulmonary acinus in hypoplastic and normal fetal rat lungs. For this purpose, a rat model of pulmonary hypoplasia in association with congenital diaphragmatic hernia (CDH) induced by Nitrofen (100 mg on day 10 of pregnancy) was studied. Sections (5 microns) from lungs of control and Nitrofen-exposed fetal Sprague Dawley rats with or without CDH aged 18-22 days (vaginal plug on day 1, birth on day 23) were stained with hematoxylin and eosin. To identify developing alveolar epithelial cells, sections were incubated with anti-surfactant protein A (SP-A; rabbit anti-mouse) or preimmunization serum (indirect immunofluorescence). On days 18 and 19, control lungs and exposed lungs from fetuses with and without CDH looked similar (pseudoglandular stage of lung development). The prospective pulmonary acinus consisted of acinar tubules with small round lumens, lined by cuboid, fluorescent type II cells. Morphometric analysis on day 19 showed significantly smaller lung volumes and lung tissue volumes after Nitrofen exposure. On day 20 (canalicular stage), some tubules were slightly dilated and lined by cuboid and thinner fluorescent cells; these dilated tubules were less numerous in lungs from exposed fetuses with CDH. On days 21 and 22 (saccular stage), the saccular lining consisted of cuboid to thin fluorescent cells in exposed lungs from fetuses with and without CDH, and fluorescent (low) cuboid cells interspersed with dark zones (type I cell areas) in control lungs. In the exposed lungs from fetuses with CDH, the lumens of all airspaces were frequently slit-like, and the septa were thicker. These phenomena gave the lungs a primitive, compact aspect. Morphometric analysis on day 22 showed smaller lung volumes and lung tissue volumes, smaller airspace/tissue ratios, smaller epithelial surface areas, and more type II cells per surface area in Nitrofen-exposed lungs than in normal control lungs. The results suggest that Nitrofen-exposed, and thus hypoplastic, fetal rat lungs are retarded with respect to the differentiation of cuboid type II cells into squamous type I cells whether or not CDH is present, and with respect to the development of the future airspaces between days 20 and 22 if CDH is present. PMID- 7882904 TI - Cadmium chloride and cadmium metallothionein-induced pulmonary injury and recruitment of polymorphonuclear leukocytes. AB - Pulmonary exposure of rats to either cadmium chloride (CdCl2) or cadmium metallothionein (CdMT) was previously reported to induce an influx of polymorphonuclear leukocytes (PMNs) to the airways, but only CdCl2 caused a significant increase in lung permeability, indicative of damage to the pulmonary epithelium. The purpose of this study was to investigate mechanisms of PMN recruitment following exposure to these forms of cadmium. Fischer 344 rats were intratracheally instilled with 10 micrograms cadmium in the form of CdCl2 or CdMT, and the time course of pulmonary inflammation and PMN migration activity was determined. PMN numbers, permeability, and PMN migration activity of lung lavage supernatant peaked 1 to 2 days after CdCl2 exposure. PMN migration activity was not detected 5 h after CdMT exposure, despite a peak of PMN numbers 10 h after exposure, but was increased by 1 day when permeability had increased to a small but significant degree. Elastase-modified forms of alpha-1-proteinase inhibitor (alpha 1PI), with molecular weights of 80 and 51 kd, have been reported to be highly chemotactic for PMNs. Antiserum to alpha 1PI significantly inhibited PMN migration activity detected in supernatants 1 day after exposure to either CdCl2 or CdMT. The results suggest that both CdCl2 and CdMT induce the formation of high molecular weight modified forms of alpha 1PI in the airways; these factors may traverse damaged epithelium to recruit PMNs from the vasculature. Additional small or lipophilic factors, undetectable by the methods of this study, may be responsible for the early influx of PMNs following CdMT exposure in the absence of increased epithelial permeability. PMID- 7882905 TI - Tumor necrosis factor-alpha-induced lung injury and its modulation by synthetic polynucleotide: a physiologic-morphometric analysis. AB - PolyI:C, a potent interferon (IFN) inducer, protects the isolated perfused lung (IPL) against platelet-activating factor (PAF)-induced injury. Because the release of PAF is stimulated by tumor necrosis factor (TNF), this study was designed to measure the effects of polyI:C on TNF-induced lung inflammation and injury. TNF (2.5 micrograms/kg) was administered to rabbits intravenously as continuous infusion over 2 h. PolyI:C was given intraperitoneally 16 h before TNF infusion. The rabbits were then anesthetized and sacrificed, and the lungs were ventilated with 20% O2 + 5% CO2 and perfused with buffer for 60 min. Lung weight gain was recorded continuously. After perfusion, lungs were inflation fixed for light and electron microscopy with morphometric analysis. Four groups of rabbit lungs were studied: (1) control; (2) polyI:C; (3) TNF, and (4) polyI:C + TNF. Lungs in the TNF group showed increased weight gain (15.4 +/- 2.4 g/h vs. 7.1 +/- 0.5 g/h in controls, p = .02) and increased volume of inflammatory cells (261% of control). These were mostly mononuclear cells (96%), primarily located in the interstitial and alveolar compartments (80%). In the polyI:C + TNF group, the weight gain of the IPL tended to be smaller (8.3 +/- 1.8 g/h, p = .08). Total inflammatory cell volume in the IPL remained elevated (330% of control), but mononuclear cells accounted for only 60% of the cell population. Most of these cells were found in the intravascular compartment (65%) implicating mononuclear cells in the early pathogenesis of TNF-induced pulmonary capillary injury in rabbits. PolyI:C, which attenuates TNF-induced injury, also modulates effects of TNF on mononuclear cell and granulocyte infiltration in the lung. PMID- 7882906 TI - Bimodal effect of platelet-activating factor (PAF) on airways responsiveness in the rabbit. AB - The role of platelet-activating factor (PAF) to increase airways responsiveness is unclear. Since PAF has unusual dose-response characteristics in vitro, this study investigated the effects of different doses or concentrations of PAF given by intravenous and aerosol administration in anesthetized rabbits. Aerosol PAF caused a dose-dependent decrease in SGL. Intravenous administration of PAF was associated with thrombocytopenia and neutropenia, whereas aerosol administration of PAF did not alter the numbers of circulatory cells. With either administration, no inflammatory cells were recovered by lavage nor was there evidence of a gross inflammatory process within the lung. Furthermore, there was no evidence of a late asthmatic response. Intravenous PAF caused a bimodal change in airways responsiveness with a significant increase in the effective concentration causing 50% of the maximal change in SGL (EC50SGL) at low doses (0.06-06 micrograms/kg h-1) and a significant decrease in EC50SGL (an increase in responsiveness) at higher doses (1.2-2.4 micrograms/kg/h-1). Aerosol PAF decreased EC50SGL significantly at the higher doses (100-250 micrograms). These changes in EC50SGL, after both administrations, were still apparent at 3 1/2 and 4 h. In conclusion PAF has a dose-dependent, biphasic, and persistent effect on airways responsiveness, which may be independent of circulating inflammatory cells. PMID- 7882907 TI - Repeated subacute ozone exposure of inbred mice: airway inflammation and ventilation. AB - The present study was designed to assess the effects of repeated subacute ozone (O3) exposure on pulmonary inflammation and ventilation in two inbred strains of mice differentially susceptible to a single O3 exposure. Susceptible C57BL/6J (B6) and resistant C3H/HeJ (C3) mice were exposed to 0.3 ppm O3 for 48 and 72 h and, after 14 days recovery, both strains were reexposed. Airway inflammation and lung injury were assessed by counting inflammatory cells and measuring total protein content and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage (BAL) returns. Minute ventilation [VE, the product of breathing frequency (f), and tidal volume (VT)] was measured prior to and immediately following each exposure. After the initial exposure, B6 mice developed greater O3-induced increases in total protein, inflammatory cell influx, and LDH activity compared to C3 mice. In normal air, VE was also significantly elevated in B6, but not C3, mice after O3. The hypercapnic f of B6 and hypercapnic VT of C3 mice were significantly altered after O3 exposure. Reexposure to O3 caused a smaller increase in the numbers of macrophages, lymphocytes, epithelial cells, and BAL protein in both strains, and no changes in LDH activity. However, the number of polymorphonuclear leukocytes significantly increased in B6 and C3 mice as compared to the initial O3 exposure. In both strains, the ventilatory responses to normal air or hypercapnia were largely reproducible after O3 reexposure. Results indicated that differential susceptibility to O3-induced inflammation was maintained in B6 and C3 mice with O3 reexposure although the magnitude of the difference was reduced. Results also suggest that the ventilatory responses to O3 in B6 and C3 mice were reproducible with reexposure, and that airway inflammation and ventilation were not codependent. PMID- 7882908 TI - Intracellular distribution of lysozyme in rat alveolar type II epithelial cells. AB - This study investigated the intracellular distribution of lysozyme, a protein that is synthesized and secreted by rat alveolar type II epithelial (ATII) cells and alveolar macrophages, using a polyclonal antibody generated against purified rat lysozyme. Lysozyme was immunoprecipitated with this antibody from Triton X 100 lysates of ATII cells cultured on a basement membrane derived from Englebreth Holme-Swarm mouse sarcoma (EHS) and radiolabeled with 35S-methionine. ATII cells cultured on EHS basement membrane for several days were fixed and labeled with antibodies to surfactant apoprotein A (SP-A) and lgp-120 (a lysosomal glycoprotein), or lysozyme and lgp-120, and studied by confocal microscopy. Organelles were identified that stained positively for either anti-lysozyme or anti-lgp-120; a second population of organelles contained both markers. Similarly, two populations of SP-A-containing organelles were identified; one contained the lysosomal glycoprotein lgp-120. In addition, confocal images demonstrated that both SP-A and lysozyme were secreted by ATII cells, as evidenced by the accumulation of secretory products within the lumen of the cyst like aggregates. When the subcellular localization of SP-A and lysozyme was studied by analytical cell fractionation, two populations of organelles were identified that contained SP-A or lysozyme. The lighter population accounted for approximately 32% of SP-A and 33% of total intracellular lysozyme and was recovered in the same region of the gradient as secretory lamellar bodies. The more dense population co-localized with lysosomes and accounted for approximately 67% of both SP-A and lysozyme recovered. Western blots of cell fractions revealed intact lysozyme in all the cell fractions. The results of these experiments suggest that lysozyme has a similar intracellular distribution as surfactant apoprotein A in ATII cells. Lysozyme is found in fractions containing lamellar bodies where it is packaged for secretion, and in lysosomal fractions where it may undergo degradation. PMID- 7882910 TI - Biopersistence of respirable synthetic fibers and minerals. September 7-9, 1992, Lyon, France. Proceedings. PMID- 7882909 TI - Silica increases tumor necrosis factor (TNF) production, in part, by upregulating the TNF promoter. AB - Silica causes release of tumor necrosis factor (TNF) from mononuclear phagocytes. One hypothesis is that silica increases TNF production, in part, by upregulating the TNF gene. To evaluate this hypothesis, THP-1 cells (a myelomonocytic cell line) were exposed to various amounts of silica and then the TNF gene transcription was evaluated. In this study silica caused a dose-dependent increase in TNF mRNA and the peak response occurred at 3 h following stimulation. A transient transfection assay also showed that silica upregulated expression of a TNF CAT construct in THP-1 cells. Furthermore, a nuclear run-on assay demonstrated that silica particles induce increased TNF gene transcription in exposed cells. THP-1 cells cultured for various periods of time in the presence of silica released TNF into the cell supernatants. These studies show that silica can upregulate the TNF gene, which results in the release of TNF protein from the cells. PMID- 7882911 TI - Dissolution of man-made vitreous fibers in rat alveolar macrophage culture and Gamble's saline solution: influence of different media and chemical composition of the fibers. AB - The effect of different chemical compositions of man-made vitreous fibers (MMVF) on their dissolution by alveolar macrophages (AM) in culture and in Gamble's solution was studied. The fibers were exposed to cultured rat AMs, culture medium alone; or Gamble's saline solution for 2, 4, or 8 days. The dissolution of the fibers was studied by measuring the amount of silicon (Si), iron (Fe), and aluminum (Al) in each medium. The AMs in culture dissolved Fe and Al from the fibers but the dissolution of Si was more marked in the cell culture medium without cells and in the Gamble's solution. The dissolution of Si, Fe, and Al was different for different fibers, and increased as a function of time. The Fe and Al content of the fibers correlated negatively with the dissolution of Si by AMs from the MMVF, i.e., when the content of Fe and Al of the fibers increased the dissolution of Si decreased. These results suggest that the chemical composition of MMVFs has a marked effect on their dissolution. AMs seem to affect the dissolution of Fe and Al from the fibers. This suggests that in vitro models with cells in the media rather than only culture media or saline solutions would be preferable in dissolution studies of MMVFs. PMID- 7882912 TI - Characterization of exposure and dose of man made vitreous fiber in experimental studies. AB - The use of fibrous test materials in in vivo experiments introduces a number of significant problems not associated with nonfibrous particulates. The key to all aspects of the experiment is the accurate characterization of the test material in terms of fiber length, diameter, particulate content, and chemistry. All data related to fiber properties must be collected in a statistically sound manner to eliminate potential bias. Procedures similar to those outlined by the National Institute of Occupational Safety and Health (NIOSH) or the World Health Organization (WHO) must be the basis of any fiber characterization. The test material to which the animal is exposed must be processed to maximize the amount of respirable fiber and to minimize particulate content. The complex relationship among the characteristics of the test material, the properties of the delivery system, and the actual dose that reaches the target tissue in the lung makes verification of dose essential. In the case of man-made vitreous fibers (MMVF), dose verification through recovery of fiber from exposed animals is a complex task. The potential for high fiber solubility makes many of the conventional techniques for tissue preservation and digestion inappropriate. Processes based on the minimum use of aggressive chemicals, such as cold storage and low temperature ashing, are potentially useful for a wide range of inorganic fibers. Any processes used to assess fiber exposure and dose must be carefully validated to establish that the chemical and physical characteristics of the fibers have not been changed and that the dose to the target tissue is completely and accurately described. PMID- 7882913 TI - Biopersistence of respirable synthetic fibers and minerals: the point of view of the epidemiologist. AB - Biopersistence of fibers and minerals in human respiratory tissues is an important aspect of the toxicity of these agents. However, few data are available from human studies. Although a number of studies have measured the lung burden of asbestos and other minerals in exposed humans, few presented information relevant to biopersistence of these agents. The studies analyzing asbestos lung burden in workers at different intervals following cessation of exposure suggest a linear decrease in concentration over time, that is independent of duration of exposure. However, the available evidence on asbestos is too sparse to allow a firm conclusion; almost no data are available on other minerals. PMID- 7882914 TI - The role of clearance and dissolution in determining the durability or biopersistence of mineral fibers. AB - It is generally accepted that to cause pulmonary disease, mineral fibers must be relatively long and thin but also able to remain in the lung for long periods. This "biopersistence" of fibers is limited by two main mechanisms of fiber clearance: removal by macrophages after phagocytosis and, for some fibers, by actual dissolution. The relative importance of these mechanisms has not been properly evaluated for any type of fiber and will certainly vary with mineral type. The efficiency of macrophage clearance is greatest with short fibers (< 5 microns long) and is reduced as fibers get longer. Fibers > 50 microns long cannot be cleared by macrophages and for some mineral types they may remain in the lung permanently. Others may fracture into shorter lengths, perhaps aided by chemical dissolution, and thus become susceptible to macrophage clearance. However, for a number of areas relating to fiber removal from the lung parenchyma detailed information is still needed: Do dusts differ in their ability to attract macrophages and stimulate these cells to phagocytosis? Following dust uptake what controls the movement of macrophages? Some may penetrate to the interstitium, some phagocytosing fibers in interstitial sites may migrate back to the alveolar space. Some move to the mucociliary escalator and some to the lymphatics. Some, most importantly, move to the pleura. Fibers are found and phagocytosed in the interstitium during the early stages of disease development, but with time many fibers appear isolated in areas of fibrous tissue. Are such fibers subsequently ignored or can they reenter the disease process after years of isolation? Finally, can phagocytosis by macrophages effect dissolution of fibers?(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882915 TI - In vivo evaluation of chemical biopersistence of nonfibrous inorganic particles. AB - The lung's response to deposited particles may depend upon the physical-chemical properties of the particles, the amount initially deposited, and the persistence of the particles. Clearance involves mucociliary transport as well as the action of phagocytic cells in nonciliated regions of the lung. Depending on the animal species studied, particle type, and particle load, inorganic materials are ingested by macrophages on alveolar surfaces with half-times of 0.6 to 7 hr. Particle-laden macrophages may migrate to airways, but we believe that an important mechanism of clearance is the dissolution of particles within alveolar macrophages and the subsequent translocation of dissolved materials to the blood. Particle dissolution in situ has long been recognized but was often thought to be carried out extracellularly in the alveolar lining layer, airway mucus, or interstitial fluid. However, many particles such as cobalt oxide or iron oxide which dissolve very little in simulated lung fluid, are solubilized more rapidly within alveolar macrophages. Clearance of particles from the lungs can be followed by a number of techniques, both invasive and noninvasive. The approaches vary in expense and resolution, and can be directed toward quantifying mechanical removal of particles versus their intracellular dissolution. Noninvasive methods permit repeated measurements of particle retention in the lungs of the same animal or human and thus allow replications and serial measurements. Greater precision with respect to the sites of retention and redistribution is achieved with quantitative morphometric methods that utilize fixation followed by physically dividing the respiratory tract into individual pieces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882916 TI - In vivo evaluation of chemical biopersistence of man-made mineral fibers. AB - Techniques developed at the Harwell Laboratory for the determination of the biopersistence of man-made mineral fibers (MMMF) in vivo are described. Results obtained with samples of glass fiber with a range of compositions, and with a sample of rockwool, are summarized. With glass fibers the rate of dissolution of fibers in vivo depends not only on their chemical composition, but also on their length. Certainly, for all fibers exceeding 10 microns in length, the longer the fiber the more rapidly it dissolves. This effect is attributed to differences in the microenvironments to which long and short fibers are exposed. Although this phenomenon appears to operate with all glass fibers, it may not apply to other types of MMMF that dissolve more readily in environments with low pH. Finally, the article examines the validity of the intratracheal method of administration for studying the biopersistence of MMMF in vivo and the use of the rat for this purpose. PMID- 7882917 TI - Relationship between lung biopersistence and biological effects of man-made vitreous fibers after chronic inhalation in rats. AB - This article describes the relationship between fiber biopersistence and the chronic toxicity of different chemical compositions of man-made vitreous fibers (MMVF) in the lung. Rats were exposed in "nose-only" inhalation chambers, 6 hr/day, 5 days/week, for 24 months to aerosol concentrations of 30 mg/m3 containing comparable fiber numbers and similar dimensions of fibrous glass (FG) or refractory ceramic fiber (RCF). Interim sacrifices were performed periodically to monitor fiber number and dimensions in the lung and the progression of pulmonary alterations. At each interim sacrifice, three to six recovery animals were removed from each exposure group and held until two years to determine the biopersistence of fibers after different exposure times. Fibers were recovered from the ashed lungs, counted, and measured using optical and scanning electron microscopy (SEM). Fiber chemistry was assessed in 91-week recovery lungs using energy dispersive spectroscopy (EDS) analysis. RCF induced lung fibrosis and an elevation in lung tumors and pleural mesotheliomas. FG exposure resulted in no lung fibrosis, no statistically significant increase in the lung tumor incidence, and no mesotheliomas. After two years of continuous exposure, the number of World Health Organization fibers per milligram dry lung recovered from RCF and FG exposed lungs was comparable. EDS analysis of recovery lungs showed that most of the alkalis and alkaline earths had leached from the FG fibers over time. A slight change in RCF chemistry was observed. These findings indicate that the change in the chemical composition of fibers may be an important determinant of the chronic toxicity of MMVFs. PMID- 7882918 TI - Biopersistences of man-made vitreous fibers and crocidolite fibers in rat lungs following short-term exposures. AB - Biopersistence of commercial man-made vitreous fibers (MMVF) and crocidolite were studied in Fischer 344 rats. MMVF used were size-selected to be rat-respirable, and rats were exposed nose-only 6 h/day for 5 days to gravimetric concentrations (30 mg/m3) of two fiber glass compositions--a rockwool, and a slagwool--or to 10 mg/m3 of long-fibered crocidolite, or to filtered air. Animals were sacrificed at 1 hr, 1, 5, 31, 90, 180, 270, 365, and 545 days after exposure stopped. Fibers were recovered from digested lung tissue to determine changes in concentrations (fibers/mg dry lung) and fiber retentions (expressed as percent of day 1 retention [PR]) for selected dimension categories. One-day average concentrations of lung-retained MMVF and crocidolite fibers, of diameter > or = 0.5 micron or > 20 microns in length, were nearly equal, permitting direct comparisons between MMVF and crocidolite. At 270 days average PR for MMVF > or = 0.5 micron in diameter were from 3 to 6 +/- 2% and 27 +/- 9% for crocidolite. For fibers > 20 microns, PR were 1 to 4 +/- 4% for MMVF and 37 +/- 20% for crocidolite. At 545 days, MMVF > 20 microns in length were at background level while concentration of crocidolite fibers > 20 microns in length remained at 2000 +/- 400 f/mg DL (dry lung), or 38 +/- 9% of day-1 retention. These results suggest strongly that MMVF dissolved or fractured in vivo whereas crocidolite fibers did not change. PMID- 7882919 TI - Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies. AB - At the same time that carcinogenicity of very thin glass fibers after intrapleural and intraperitoneal (ip) administration was demonstrated (1,2) researchers found that gypsum fibers and HCI-leached chrysotile fibers were easily soluble in the peritoneal cavity. This led to the conclusion that the chemical composition of fibers was not responsible for the carcinogenesis but that the degree of carcinogenic potency of a fiber depended on the extent to which it retained its fibrous structure. A thin glass fiber with a low biodurability did not induce tumors after ip injection of a high dose, although the ip test had been criticized for being "overly sensitive." The ip model has been the most successful for determining carcinogenicity of inorganic fibers and establishing dose-response relationships; but to determine the possibilities and limitations of this test model, very high doses of nonfibrous silicon carbide and of a slightly durable glass fiber type were injected ip in Wistar rats. No obviously acute or chronic toxic effect was observed in 90 weeks, but there was a 40% incidence of serosal tumors in the group treated with glass fibers. A pilot study on the persistence of slag fibers in the omentum of rats after ip injection showed a half-time of about 1 year. It was calculated that an ip injection of 10(9) fibers would lead to a concentration of fiber numbers in the ash of the omentum in the same range as the concentration in the lung after 2 years of inhalation exposure. The long-term inhalation study with fibers in rats has been called the "gold standard" for risk characterization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882920 TI - An experimental approach to the evaluation of the biopersistence of respirable synthetic fibers and minerals. AB - The biopersistence of fibers and minerals in the respiratory tract is an important parameter in the toxicity of those materials. The biopersistence of respirable synthetic fibers and minerals in man can be most closely evaluated in an animal model. While acellular and in vitro systems are important for initial evaluation of solubility and durability, they cannot simulate the dynamics of inhalation deposition and clearance and the subsequent systemic reaction to fibers and minerals that occurs in the animal. To evaluate the biopersistence of synthetic fibers, male rats were exposed to a well defined rat respirable aerosol of man-made vitreous fibers (MMVF), 6 hr/day for 5 days. Following exposure, subgroups were sacrificed at intervals ranging from 1 hr to 52 weeks. Following sacrifice, the lungs were removed, weighed, and immediately frozen at 20 degrees C for subsequent digestion by low temperature plasma ashing. The number, size distribution, and chemical composition of the fibers in the aerosol and lung were determined. With this animal model the role of biopersistence in altering the geometry and clearance of fibers can be systematically evaluated. The model also can be applied for the evaluation of the biopersistence of nonfibrous minerals. PMID- 7882921 TI - Biopersistence of inhaled organic and inorganic fibers in the lungs of rats. AB - Fiber dimension and durability are recognized as important features in influencing the development of pulmonary carcinogenic and fibrogenic effects. Using a short-term inhalation bioassay, we have studied pulmonary deposition and clearance patterns and evaluated and compared the pulmonary toxicity of two previously tested reference materials, an inhaled organic fiber, Kevlar para aramid fibrils, and an inorganic fiber, wollastonite. Rats were exposed for 5 days to aerosols of Kevlar fibrils (900-1344 f/cc; 9-11 mg/m3) or wollastonite fibers (800 f/cc; 115 mg/m3). The lungs of exposed rats were digested to quantify dose, fiber dimensional changes over time, and clearance kinetics. The results showed that inhaled wollastonite fibers were cleared rapidly with a retention half-time of < 1 week. Mean fiber lengths decreased from 11 microns to 6 microns over a 1-month period, and fiber diameters increased from 0.5 micron to 1.0 micron in the same time. Fiber clearance studies with Kevlar showed a transient increase in the numbers of retained fibrils at 1 week postexposure, with rapid clearance of fibers thereafter, and retention half-time of 30 days. A progressive decrease in the mean lengths from 12.5 microns to 7.5 microns and mean diameters from 0.33 micron to 0.23 micron was recorded 6 months after exposure to inhaled Kevlar fibrils. The percentages of fibers > 15 microns in length decreased from 30% immediately after exposure to 5% after 6 months; the percentages of fibers in the 4 to 7 microns range increased from 25 to 55% in the same period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882922 TI - Use of the short-term inflammatory response in the mouse peritoneal cavity to assess the biological activity of leached vitreous fibers. AB - We used a special-purpose glass microfiber sample, Johns-Manville Code 100/475, to study the effects of various acid and alkali treatments on biological activity as assessed by inflammation in the mouse peritoneal cavity, the leaching of Si, and the phase contrast optical microscopy (PCOM) fiber number. We used mild and medium treatments with oxalic acid and Tris buffer and harsh treatment with concentrated HCl and NaOH. Mild oxalic acid and Tris treatment for 2 weeks had no effect on any of the end-points, but prolonging the mild oxalic acid treatment time to 2 months reduced the biological activity and the fiber number. Medium oxalic acid treatment reduced the biological activity and the fiber number and caused a loss of Si. Medium Tris alkali treatment reduced the PCOM-countable fibers and the biological activity but did not cause a substantial loss of Si. Harsh treatment with strong HCl did not affect the fiber number or cause leaching but the biological activity was reduced; strong NaOH reduced the fiber number and biological activity, and caused marked leaching of Si. The medium oxalic acid conditions (pH 1.4) were more acid than those found in lung cells but produced the same effects (reduction in fiber number and biological activity) as the more physiological mild treatment (pH 4.0), when prolonged. This study suggests that medium oxalic acid treatment can be used as a short-term assay to compare loss of Si, reduction in fiber number, and change in biological activity of vitreous fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882923 TI - Comparative investigations of the biodurability of mineral fibers in the rat lung. AB - The biodurability of various glass fibers, rockwool, and ceramic fibers was examined in rat lungs and compared with natural mineral fibers. Experiments were based on studies that have shown that the biodurability of fibers is one of the essential factors of the carcinogenic potency of these materials. Sized fractions of fibers were instilled intratracheally into Wistar rats. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM) or careful examination of the fiber suspension before treatment. After serial sacrifices up to 24 months after treatment, the fibers were analyzed by SEM following low temperature ashing of the lungs. Parameters measured included number of fibers, diameter, and length distribution at the various sacrifice dates, so that analyses could be made of the elimination kinetics of fibers from the lung in relation to fiber length (FL). Size selective plots of the fiber elimination correlated with fiber diameters enables the mechanism of the fiber elimination (dissolution, fiber breakage, physical clearance) to be interpreted. The half-time of fiber elimination from the lung ranges from about 10 days for wollastonite to more than 300 days for crocidolite. The biodurability of man-made vitreous fibers (MMVF) is between these values and is dependent on the chemical composition of the fibers and the diameter and length distribution. Results indicate that the in vivo durability of glass fibers is considerably longer than expected from extrapolation of published data on their in vitro dissolution rates. PMID- 7882924 TI - Clearance of inhaled ceramic fibers from rat lungs. AB - Deposition, clearance, retention, and durability of inhaled particles in lung are important factors for induction of pulmonary fibrosis or lung cancer. To study the deposition and clearance of aluminium silicate ceramic fibers from the lung, male Wistar rats were exposed to ceramic fibers, with a mass median aerodynamic diameter (MMAD) of 3.7 microns, for 6 hr/day, 5 days/week for 2 weeks. The average exposure concentration was 27.2 mg/m3 (SD 9.0). The rats were killed at 1 day, 1 month, 3 months, and 6 months after the end of exposure, and the fiber numbers and dimensions were measured with a scanning electron microscope. No significant difference in length of residual ceramic fibers in the lungs was found among the groups. The geometric mean diameter and number of ceramic fibers, however, decreased according to the clearance period. These findings suggest that the fibers were dissolved at their surface. PMID- 7882925 TI - Correlation between particle size, in vivo particle persistence, and lung injury. AB - Dosimetry parameters such as deposition, clearance, retention, and translocation and dissolution of inhaled particles in and to different lung compartments may be important for the persistence of particles in the lung and may correlate with adverse pulmonary effects. We investigated such correlations using a model involving TiO2 particles of two particle sizes (20 nm diameter, ultrafine; 250 nm diameter, fine) of the same crystalline structure (anatase). A 12-week inhalation experiment in rats resulted in a similar mass deposition of the two particle types in the lower respiratory tract. The ultrafine particles elicited a persistently high inflammatory reaction in the lungs of the animals compared to the larger-sized particles. In the postexposure period (up to 1 year) retention in the alveolar space per se was not different between fine and ultrafine TiO2. However, the following differences between the particle types were noted: a significantly different total pulmonary retention, both quantitatively (significantly prolonged retention of the ultrafine TiO2) and qualitatively (increased translocation to the pulmonary interstitium and persistence there of the ultrafine TiO2); greater epithelial effects (Type II cell proliferation; occlusion of pores of Kohn) and the beginning of interstitial fibrotic foci with ultrafine TiO2; significant sustained impairment of alveolar macrophage function after ultrafine TiO2 exposure as measured by the clearance of test particles. A correlation between particle surface area and effects was observed. A comparison of the adverse reactions with dosimetric parameters of TiO2 in different lung compartments in the postexposure period showed a correlation of the persistence of effects in both the alveolar and interstitial space with the persistence of particles in the respective compartment. PMID- 7882926 TI - Effect of coexposure to asbestos and kerosene soot on pulmonary drug-metabolizing enzyme system. AB - This article reports the effect of coexposure to Indian chrysotile asbestos (5 mg/rat) and kerosene soot (5 mg/rat) on the pulmonary phase I and phase II drug metabolizing enzymes 1, 4, 8, 16, 30, 90, and 150 days after a single intratracheal inoculation. Exposure to soot resulted in a significant induction of the pulmonary microsomal cytochrome P450 and the activity of dependent monooxygenase, benzo(a)pyrene (B[a]P) hydroxylase, and epoxide hydrase at all time intervals. On the other hand, the cytosolic glutathione S-transferase (GST) activity was induced at days 1, 4, 8, 16, and 30 after exposure, followed by inhibition in the enzyme activity. In contrast, chrysotile exposure depleted cytochrome P450, B[a]P hydroxylase, epoxide hydrase, and GST at initial stages, while all these parameters except GST were induced at later stages. However, coexposure to chrysotile and soot led to a significant inhibition in the cytochrome P450 levels, activities of B[a]P hydroxylase, epoxide hydrase, and GST at initial stages of exposure. At advanced stages, however, an additional increase in cytochrome P450, B[a]P hydroxylase, and epoxide hydrase but a decrease in GST was observed. These results clearly show that the intratracheal coexposure to high levels of asbestos and kerosene soot alters the metabolic activity of the lung, which is turn may retain toxins in the system for a longer period, resulting in adverse pathological disorders. PMID- 7882927 TI - Investigation on the durability of man-made vitreous fibers in rat lungs. AB - Two types of sized stonewool with median lengths of 6.7 and 10.1 microns and median diameters of 0.63 and 0.85 microns, and crocidolite with fibers of median length of 4.8 microns and median diameter of 0.18 microns were instilled intratracheally into female Wistar rats. A single dose of 2 mg in 0.3 ml saline was used for the stonewool samples and 0.1 mg in 0.3 ml saline for crocidolite. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM). Five animals per group were sacrificed after 2 days, 1, 3, 6, and 12 months. After low-temperature ashing of the lungs about 200 fibers per animal were analyzed by SEM for length and diameter. The number and mass of fibers in the total lung were calculated. For the stonewool samples the decrease in the number of fibers in the lung ash followed approximately first order kinetics resulting in half-times of 90 and 120 days. The analysis of fiber number and diameter of different length fractions was used to estimate the contribution of three processes of fiber elimination: transport by macrophages for short fibers, breakage of fibers, and dissolution of fibers. (The process of transport by macrophages was found fastest for fibers with length < 2.5 microns). For the elimination of critical fibers with length > 5 microns, the breakage and dissolution were the most important processes. The breakage of fibers was predominant for one of the stonewool samples. The preferential type of the mechanism of fiber elimination is dependent on chemical composition and size distribution. PMID- 7882928 TI - Cellular and molecular mechanisms of asbestos carcinogenicity: implications for biopersistence. AB - Carcinogenic agents can influence the carcinogenic process either by mutating critical target genes or by increasing the number of cells at risk for mutations. Cytogenetic and molecular studies of asbestos-related cancers indicate that inactivation or loss of multiple tumor suppressor genes occurs during lung cancer development. Aneuploidy and other chromosomal changes induced by asbestos fibers may be involved in genetic alterations in asbestos-related cancers. Furthermore, asbestos fibers may influence the carcinogenic process by inducing cell proliferation, free radicals, or other promotional mechanisms. Therefore, asbestos fibers may act at multiple stages of the carcinogenic process by both genetic and epigenetic mechanisms. Biopersistence is undoubtedly important in fiber carcinogenicity. However, the time required for a fiber to remain in the lung to exert a cancer-related effect is difficult to specify. PMID- 7882929 TI - Investigation of the biodurability of wollastonite and xonotlite. AB - The in vivo durability of wollastonite materials, coated and uncoated, and of xonotlite was tested. Wollastonite is an anhydrous natural silicate and xonotlite is a hydrated synthetic calcium silicate. UICC crocidolite was used as a positive control with high durability. Using a dry-sizing technique, fractions from the stock materials were prepared according to the definition of "thoracic particulate mass" and "respirable particulate mass" of the American Conference of Governmental Industrial Hygienists. Fibers were instilled intratracheally into female Wistar rats, and the evenness of their distribution in the lung was checked by scanning electron microscopy (SEM). After serial sacrifices at 2 and 14 days, 1, 3, and 6 months, and low temperature ashing of the lung, the fibers were analyzed by SEM. The number and size distribution of fibers were investigated. The total number of crocidolite fibers decreased with a half-time of 240 days, but the number of fibers > 5 microns in length was unchanged after 6 months. The elimination kinetics of wollastonite fibers from the lung were relatively fast, with half-times of 15 to 21 days. The coating of wollastonite in Wollastocoat had no effect on this elimination process. For the thoracic fraction of wollastonite, the elimination from the lung was as fast as for the respirable particulate fraction. The elimination kinetics of xonotlite from the lung was very fast. This material consisted of single crystals of acicular morphology with a median length of 1.3 micron and of agglomerates of these crystals. More than 99% of single crystals and about 85 to 89% of the agglomerates were already eliminated 2 days after instillation. PMID- 7882930 TI - Persistence of long, thin chrysotile asbestos fibers in the lungs of rats. AB - The distribution of inhaled mineral fibers in the lung determines the site and severity of disease caused by the fibers. Some of our recent work has described the fate of inhaled asbestos fibers in rodents. After a brief inhalation exposure, asbestos fibers are deposited primarily at the first alveolar duct bifurcations, and fibrotic lesions are initiated. These sites of deposition occur as close to the visceral pleura as 220 micron. Several studies have suggested that short fibers are cleared from the lung more efficiently than long ones, and our data support this view. Our laboratory has shown that aerosolized chrysotile fibers longer than 16 microns can be deposited in the peripheral lung parenchyma of rats, and the measured clearance rate of these fibers is not significantly different from zero. Chrysotile, but no amphibole, fibers split longitudinally, so that the number of retained chrysotile fibers > or = 16 microns in length increases over time. We have not observed significant changes in chemical composition of chrysotile fibers up to 30 days post-deposition in the rat. Nor have we observed translocation of chrysotile fibers from the "central" regions of the lung toward the subpleural regions. However, 1 month after a single 3-hr exposure to chrysotile asbestos, the longest, most pathogenic fibers persist throughout the lung parenchyma. These retained fibers have the potential to cause disease in both parenchyma and pleura. PMID- 7882931 TI - One-year follow-up of the phagocytic activity of leukocytes after exposure of rats to asbestos and basalt fibers. AB - The phagocytic activity of leukocytes in peripheral blood was investigated after 2, 24, and 48 hr; 1, 2, 4, and 8 weeks; and 6 and 12 months following intraperitoneal administration of asbestos and basalt fibers to Wistar rats. Asbestos and basalt fibers differed in their effects on the parameters studied. Both granulocyte count and phagocytic activity of leukocytes during the 1-year dynamic follow-up in both dust-exposed groups of animals changed in two phases, characterized by the initial stimulation of the acute phase I, followed by the suppression of the parameters in the chronic phase II. Exposure to asbestos and basalt fibers led, in phase II, to impairment of the phagocytic activity of granulocytes. Asbestos fibers also significantly decreased phagocytic activity of monocytes. Exposure to basalt fibers did not affect the phagocytic activity of monocytes in phase II. Results suggest that the monocytic component of leukocytes plays an important role in the development of diseases caused by exposure to fibrous dusts, but basalt fibers have lesser biological effects than asbestos fibers. PMID- 7882932 TI - Solubility of chrysotile asbestos and basalt fibers in relation to their fibrogenic and carcinogenic action. AB - Fiber length and persistence are thought to be determinants for the development of toxic, fibrogenic, and carcinogenic effects of fibrous dusts. When the solubilities of chrysotile asbestos (CA) and basalt fibers (BF) were compared by measuring the loss of silica and magnesium in Leineweber's solution, CA was shown to be the more soluble. In a 6-month inhalation experiment, chrysotile at a mean concentration of 25 mg/m3 had a higher clearance rate than other comparable dusts. In acute toxicity studies, chrysotile and basalt fibers were administered intraperitoneally. At a dose of 1.7 g/kg body weight of CA, one third of the animals died. A dose of 2.7 g/kg body weight killed all the animals. With BF, even at a dose of 10 g/kg body weight all the animals survived. When the two fibers were administered over a 6-month period, either intratracheally or by inhalation, fibrotic lesions were more common in the group that received CA. Intraperitoneal administration of CA led to three times as many deaths from peritoneal mesothelioma as administration of BF. It appears, therefore, that in spite of its higher solubility and lower persistence, CA was the more toxic, fibrogenic and carcinogenic fiber, which gives rise to the hypothesis that the surface chemistry of the fibers is the determinant for biological activity. PMID- 7882933 TI - Chronic inhalation and biopersistence of refractory ceramic fiber in rats and hamsters. AB - Lifetime "nose-only" inhalation studies were conducted in rats using four types of refractory ceramic fibers (FCF), 1 micron in diameter x 22 to 26 microns length: High Purity, Kaolin, Zirconia, and After-Service; and on hamsters using Kaolin RCF. For comparison, animals also were exposed to chrysotile fibers. Rats were exposed 6 hr/day, 5 days/week for 24 months to concentrations ranging between 3 and 30 mg/m3. Time- and dose-dependent lesions in the rat included the development of interstitial fibrosis, pleural fibrosis, pulmonary tumors, and mesothelioma. Exposure to 3, 9 or 16 mg/m3 produced no excess lung tumors; no fibrosis was seen at 3 mg/m3. A significant increase in lung tumors and interstitial fibrosis was observed at 30 mg/m3. A single mesothelioma was observed in rats exposed to 9 mg/m3, while two occurred at 30 mg/m3. Hamsters were similarly exposed to 30 mg/m3 Kaolin RCF for 18 months; no lung tumors were induced, but pulmonary and pleural fibrosis were observed and there was a 42% incidence of mesothelioma. Multiple interim sacrifices together with recovery animals allowed detailed assessment of the lung burden of RCF, which was found to be dose related and, at the high doses, exceeded 10(5) fibers/mg of dry lung. During the various recovery periods there was a clear reduction in fiber burden. Mathematical modeling of these data for deposition, clearance, and retention and for species is currently underway. PMID- 7882934 TI - Enhanced translocation of particles from lungs by jaggery. AB - Because industrial workers in dusty or smoky environments seemed to experience no discomfort if they consumed the sugar cane product jaggery, experimental studies were undertaken to observe the effects of jaggery on dust-exposed rats. Rats with and without a single intratracheal instillation of coal dust (50 mg/rat) were orally gavaged with jaggery (0.5 g/rat, 5 days/week for 90 days). The enhanced translocation of coal particles from lungs to tracheobronchial lymph nodes was observed in jaggery-treated rats. Moreover, the jaggery reduced the coal-induced histological lesions and hydroxyproline contents of lungs. The lesions induced in omental tissue and regional lymph nodes by a single intraperitoneal injection of 50 mg each of coal and silica dust were modified by jaggery (0.5 g/rat, 5 days/week for 30 days). These findings along with the preventive action of jaggery on smoke-induced lung lesions suggest the potential of jaggery as protective agent for workers in dusty and smoky environments. PMID- 7882935 TI - Pulmonary deposition and clearance of glass fiber in rat lungs after long-term inhalation. AB - In this study Wistar male rats were exposed to glass fiber obtained by the disintegration of a binderless glass fiber filter, for 6 hr/day, 5 days/week for 12 months. The mass median aerodynamic diameter (MMAD) of the fiber, determined with an Andersen sampler, was 2.6 microns. The count median diameter and length of the fibers measured by scanning electron microscopy (SEM) were 0.51 and 5.5 microns, respectively. The daily average exposure fiber concentration was 2.2 +/- 0.6 mg/m3. Some rats were sacrificed 24 hr after removal from the exposure chamber following the 12 months' exposure. Others were sacrificed 12 months after the end of exposure. The wet organ weights were recorded at the time of death and the silicon content of the lungs was determined by absorption spectrophotometry. After 12 months' exposure, the amount of glass fiber retained in the rat lungs was 1.49 mg, and after 12 months' clearance it was 0.61 mg. The biological half life in a single exponential model was to be 8.7 months, much longer than the predicted value of 1.5 months obtained in a previous experiment in which rats were exposed for 4 weeks to the same glass fiber. PMID- 7882936 TI - Possible application of urinary analysis to estimate dissolution of some man-made vitreous fibers. AB - A preliminary study at the institut National de l'Environnement Industriel et des Risques (INERIS) examined the dissolution of three man-made vitreous fiber samples (glasswool, rockwool, glass microfibers: JM 100) after intraperitoneal injections in male Wistar rats. The chemical composition of the original fibers was determined by inductively coupled plasma spectrometry (ICP). The urine of the rats was collected at fixed times between day 1 and day 204, and the ICP was used to look for elements known to be present in the original fibers. At day 204, a piece of omentum was removed at autopsy, ashed and analyzed by energy dispersive X-ray analysis (EDXA) to identify the elements remaining in the fibers. Silicon and aluminium were retained in the fibers from all samples at day 204. Losses in calcium, sodium, magnesium, and sulfur were observed, but these elements were not studied in the urine samples because they are naturally present in relatively high concentrations in rat cells and biological fluids. Although there was a loss of zinc from the glass microfibers, no corresponding difference was observed between the zinc levels excreted by the treated animals and by the controls. Similarly, despite the loss of manganese from the rockwool fibers at day 204, none was detectable in the urine samples. Titanium, present at the 0.3% level in rockwool, was not detectable by EDXA at day 204, but small quantities were detected in the first 2 weeks in the urine samples of rats treated with rockwool.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882937 TI - Epidemiological significance of mineral fiber persistence in human lung tissue. AB - For the experimentalist, mineral fiber persistence may provide clues to disease mechanisms, for the epidemiologist, to the measurement of exposure. Qualitatively, this can be valuable when unsuspected exposures have been demonstrated as, for example, MMMF workers exposed to amosite or chrysotile workers to tremolite. Quantitatively, the potential of lung burden analyses to assess lifetime mineral fiber exposure has yet to be achieved with confidence. The difficulties are 2-fold, the first related to sampling and the second to the dynamics of biopersistence. Until some noninvasive method is found to identify and quantify numerically inorganic fibers in human tissue during life, epidemiological studies must depend on lung samples obtained at autopsy or thoracic surgery. This source is inevitably subject to seriously large and indefinable bias of various kinds. Of equal importance is the present uncertain state of knowledge concerning factors that determine what is present in the lung at any time. These determinants clearly include the dimensional features of airborne environmental particulates and characteristics that affect their durability in tissue. PMID- 7882938 TI - Biopersistence of man-made vitreous silicate fibers in the human lung. AB - There is now a substantial body of experimental data on the pulmonary biopersistence of man-made vitreous silicate fibers (MMVSF), but human data are seriously lacking. Our knowledge in this field is essentially limited to a few reports of measurements of fibers retained in lung tissue samples taken at autopsy from workers manufacturing these products. Three types of exposure were studied: fibrous glass, mineral wool, and refractory ceramic fibers. Overall, the available data do not provide evidence for substantial long-term retention of fibers in the human lung after occupational exposure to MMVSF dusts. A word of caution, however; the amount of data supporting the previous statement is much greater for fibrous glass than for either mineral wool or refractory ceramic fibers. There is no human data on the key question of the kinetics of pulmonary clearance of inhaled MMVSF. PMID- 7882939 TI - Persistence of natural mineral fibers in human lungs: an overview. AB - Virtually all available data on persistence of naturally occurring mineral fibers in human lungs have been derived from studies of asbestos fiber loads. These studies indicate that, although both amphibole and chrysotile asbestos fibers are found in the lungs of the general population and exposed workers, amphibole fibers are universally present in disproportionately large and chrysotile fibers in disproportionately small amounts compared to their known abundance in the original inhaled dusts. Why this should be remains unclear. Most reports have shown that fiber accumulation is proportional to measured exposure for amphiboles, but this is not generally true for chrysotile. Very little information is available on actual fiber clearance rates from human lungs. For amosite and crocidolite, estimated clearance half-times are measured in years to decades, whereas for chrysotile the available, rather indirect, data suggest that the vast majority of fibers are cleared within months, although some fibers may be sequestered and very slowly cleared. Overall these studies suggest that the differences between amphibole and chrysotile fiber burdens in man reflect much faster clearance of chrysotile fibers, rather than a failure of chrysotile deposition. A variety of other naturally occurring fibers are commonly found in human lungs, but there are no data on their rates of accumulation or disappearance. PMID- 7882941 TI - Influence of particle size and chemical composition on efficiency of clearance mechanisms: electron microscopy studies on humans. AB - This article compares the presence of solid particles in lung parenchyma samples collected from accident victims and in bronchoalveolar lavage fluid taken from patients diagnosed with pulmonary carcinoma. Analysis by electron microscopy showed differences in particle size between the two groups, which could be attributable both to differences in original particle size and to their solubility in the biological environment. PMID- 7882940 TI - Chrysotile biopersistence in the lungs of persons in the general population and exposed workers. AB - Lung burden analysis was performed on 126 autopsy cases of persons who died in New York City from 1966 through 1968. Of the 126 cases, 107 were probably non occupationally exposed, judging by occupational history and asbestos body content of lung. Fifty-three of the 107 cases contained short chrysotile fibers/fibrils, < 5 microns in length, present in 3-fold greater amounts than were found in laboratory background controls. The fiber concentrations ranged from 1.8 to 15.7 x 10(6) f/gm/dry lung tissue, and the proportion of fibers > or = 5 microns in length was only 0.34% of the total chrysotile population found. Other inorganic particles present included fragments of amphiboles. In contrast to these data, the lung parenchyma of persons occupationally exposed to asbestos commonly showed the presence of other fiber types, especially amosite and crocidolite, at very much higher concentrations and greater fiber length. Any chrysotile present would usually be in fiber bundle form, with both fibers and fibrils > 5 microns in length. Comparison of the lung fiber content of occupationally exposed persons with that of the general population showed marked qualitative and quantitative differences. Fibers are durable, and are retained in a range of concentrations. Their length and dose, among other factors, which control their biological potential are different in the two populations; the risk factors for chrysotile induced disease are not the same. PMID- 7882942 TI - Lung content analysis of cases occupationally exposed to chrysotile asbestos. AB - The lung contents of six workers who had been occupationally exposed to chrysotile asbestos were examined. Five were lung cancer cases from Quebec, Canada. The sixth, an American worker who had developed pleural mesothelioma, was particularly interesting, with the lung content strikingly distinct from the Canadian cases; chrysotile, the predominant fiber in his lung, was present at a concentration 300 times that of the average total fiber content in the Canadian cases. The fiber length distribution of the chrysotile recovered from the U.S. mesothelioma case was indistinguishable from that of chrysotile specimens known to produce mesotheliomas in rats. It was also found that the characteristics of the calcium-magnesium-iron silicate fibers present in all six cases were not readily comparable to tremolite asbestos specimens known to induce mesotheliomas in animals. PMID- 7882943 TI - In vitro assessment of the biopersistence of vitreous fibers: state of the art from the physical-chemical point of view. AB - Biopersistence is a function of different parameters: low solubility of the vitreous phase in physiological media, good mechanical properties of altered fibers, limited ability of phagocytosis to digest residual fragments. This article emphasizes solubility problems. From studies related to nuclear waste storage and other industrial problems, the mechanisms (formation of a leached layer of variable thickness and structure) and the kinetic laws describing the dissolution of vitreous fibers are now fairly well known. Appropriate methods depend only on the composition of the vitreous fibers that have to be chosen to determine intrinsic dissolution rates. All other parameters influencing the dissolution rate have to be fixed radius of the fibers, composition of the saline solution) or within a convenient range (flow-rate, s/v ratio). Alternatively, physicochemical parameters may be derived from a known relation (Arrhenius plot for T, kinetic equation for pH, geometrical equation for S). In spite of their widespread use, flow-through systems, in our opinion, give less precise kinetic results than large-volume closed systems with small s/v ratios (less than 0.5 cm 1). In closed and open systems, we suggest the use of two parameters for describing the dissolution rates at 37 degrees C: the initial rate constant, vo, and the time constant, k, for a rate decreasing at variable S. PMID- 7882944 TI - Environmental asbestotic pleural plaques in northeast Corsica: correlations with airborne and pleural mineralogic analysis. AB - We report a prevalence study of environmental pleural plaques in subjects over 50 years old from the northeastern Corsican village of Murato, built on asbestos surface deposits. The percentage of plaques was 41%, versus 7.5% in the control village of Vezzani. Although surface deposits contain both chrysotile and tremolite, airborne pollution and asbestos lung burden of exposed inhabitants consist essentially of tremolite as assessed by transmission electron microscopy (TEM). However, TEM analysis of the parietal pleura of three animals bred in exposed areas showed a predominance of short fibers of chrysotile. The respective roles of tremolite and chrysotile in inducing pleural plaques in Corsica should thus be considered. PMID- 7882945 TI - Retention of asbestos fibers in the human body. AB - The number, type, and size of retained asbestos fibers were measured by scanning electron microscopy (SEM) in lung tissues of 10 workers who had died from lung cancer or mesothelioma. The levels were 190-3000 x 10(6) fibers/g of dry tissue in three crocidolite sprayers, 6-39 x 10(6) fibers/g of dry tissue in two asbestos product workers and 13-280 x 10(6) fibers/g of dry tissue in five insulators exposed to anthophyllite. The duration of past exposure corresponding to the limit of 1 million fibers/g of dry tissue was 1 to 2 days in spraying, 3 to 10 days at the production plant and 1 to 4 months in insulation work. No long term clearance of amphibole fibers, > 5 microns in length, could be demonstrated. In one of the sprayers the fiber concentrations of lung parenchyma, visceral and parietal pleura, hilar lymph nodes, and kidney cortex were orders of magnitude higher than in a series of unselected autopsies. The size and aspect ratio of crocidolite fibers in various tissues were similar, indicating that the translocation processes are rather unselective in respect to fiber dimensions. PMID- 7882946 TI - Comparative analysis of inhaled particles contained in human bronchoalveolar lavage fluids, lung parenchyma and lymph nodes. AB - Translocation of inhaled particles from the alveolar spaces to lung parenchyma and lymph nodes is one of the mechanisms that determine the biopersistence of particles. This study compares the nonfibrous particulate burden in bronchoalveolar lavage (BAL) fluids, lung parenchyma, and thoracic lymph nodes and attempts to detect the degree of differentiation, if any, based on particle size or type. This comparison can only be done on BAL, lung parenchyma, and lymph node samples collected from the same subject over a short time. Patients undergoing surgical lung resection are suitable for this purpose. Particles recovered by digestion-filtration were counted, sized, and analyzed by analytical transmission electron microscopy. Total particle load ranges grossly between 10(5) to 10(7) p/ml in BAL, 10(9) to 10(10) p/g dry tissue in parenchyma and 10(10) to 10(11) p/g dry tissue in lymph nodes. Diameters are log-normally distributed and mean diameters range between 0.5 to 0.9 micron. Nonlamellar silicate particles have a significantly larger diameter in lymph nodes. Differences in particle type between the three sampling sites are small and nonsystematic. PMID- 7882947 TI - Fiber levels and disease in workers from a factory predominantly using amosite. AB - The Cape Boards Plant at Uxbridge produced insulation board containing amosite asbestos between 1947 and 1973 with only small amounts of chrysotile. After 1973 only amosite was used. In this study we examined lung samples from 48 workers who had been employed at the plant and who had come to autopsy. The study investigated the fiber levels against the lung pathology including amount of interstitial fibrosis and numbers of ferruginous bodies. The degree of interstitial fibrosis and number of asbestos bodies were graded and the tissues were analyzed by transmission electron microscopy and energy dispersive X-ray analysis and the fibers counted and typed. The 48 cases included 5 mesotheliomas and 14 lung cancers. The mineral analysis results were dominated by the amosite fiber levels. The amounts of chrysotile were relatively small. There were higher levels in lung cancer cases than mesotheliomas and higher levels in mesothelioma cases than those who had died from nonasbestos related diseases. Analysis of the lung tissues showed a consistent pattern of high amosite levels, which confirms the impression that amosite was the predominant form of asbestos used and also indicates that the factory had been a very dusty one. PMID- 7882948 TI - Biopersistence of the mineral matter of coal mine dusts in silicotic human lungs: is there a preferential release of iron? AB - Toxic potency of quartz-containing dusts, including coal mine dusts, is usually inhibited by protective clay mineral layers on the surface of quartz particles. This investigation of 11 dusts recovered from lungs of coal miners with different silicosis grade shows that such layers persist during long-term contact with human lung tissues. On the other hand, the results suggest that an apparently preferential release of iron occurred in lungs with massive fibrosis. These preliminary results support the hypothesis of an iron-related harmfulness of coal mine dusts. PMID- 7882949 TI - Biopersistence of nonfibrous mineral particles in the respiratory tracts of subjects following occupational exposure. AB - Transmission electron microscopy analysis (TEMA) was used to analyze the bronchoalveolar lavage fluid (BALF) of 262 subjects occupationally exposed (OE) to nonfibrous mineral particles (NFMP) and 42 controls not occupationally exposed to mineral dusts. OE subjects were divided into three groups according to the lapse of time since last exposure: < or = 1 year and < 10 years (E2), > or = 10 years (E3). The total BALF mineral particle concentration was significantly higher in OE patients than in controls and was closely related to the time lapse since last exposure to NFMP (median values for OE, 7.7 x 10(5) particles/ml; E1, 9 x 10(5) particles/ml; E2, 5 x 10(5) particles/ml; E3, 4.3 x 10(5) particles/ml; controls, 2 x 10(5) particles/ml). No statistical difference was observed for age and smoking habits between OE and control subjects. Concentrations of crystalline silica and metals (exogenous iron, aluminum, metallic alloys and other metals) were significantly higher in OE subjects than in controls, and even though these mineral concentrations decreased with increasing time since last occupational exposure, they still remained higher in the E3 group than in controls. Crystalline silica and metals were thus identified as biopersistent NFMP in the human lung using BALF ATEM method. This method is a useful tool in assessing occupational exposure to NFMP, even when a long period has elapsed since last exposure, and may be used in studying etiology of some respiratory diseases. PMID- 7882950 TI - Role of biopersistence in the pathogenicity of man-made fibers and methods for evaluating biopersistence: a summary of two round-table discussions. AB - This paper summarizes two roundtable discussions held at the conclusion of the International Conference on Biopersistence of Respirable Synthetic Fibres and Minerals. The first round table addressed the role of biopersistence in the pathogenicity of fiber-induced disease. The panel included T. W. Hesterberg (Chairman), J.M.G. Davis, K. Donaldson, B. Fubini, N.F. Johnson, G. Oberdoerster, P. Sebastien, and D. Warheit. The second panel addressed the issue of methods for assessing biopersistence. It included R.O. McClellan (Chairman), J. Brain, A. Langer, A. Morgan, C. Morscheidt, H. Muhle, and R. Musselman. The two chairmen acknowledge the excellent contributions of all the members of the panels, whose comments formed the basis of this summary. Nonetheless, the authors assume full responsibility for the written text, recognizing that it was not reviewed by the discussants of the two panels.-Environ Health Perspect 102(Suppl 5):277-283 (1994) PMID- 7882951 TI - Introduction: INSERM-IARC-CNRS workshop on biopersistence of respirable synthetic fibers and minerals. PMID- 7882952 TI - The occupational physician's point of view: the model of man-made vitreous fibers. AB - This article gives a detailed description of the procedure the occupational physician uses in interpreting the available scientific data to provide useful information for prevention of pulmonary diseases related to man-made mineral fibers, particularly lung cancer and mesothelioma. As it is difficult to reach definite conclusions from human data on the toxicity of specific fibers, an experimental approach is needed. Concerning animal data, we emphasize that adequate inhalation studies are the "gold standard" for extrapolating to humans. However, experiments using intracavitary injection or cells in vitro may represent indicative tests for a possible carcinogenic effect. Such tests should be used to assess the intrinsic carcinogenicity of fibers, but they must be confirmed by adequate inhalation models. Despite the present uncertainties, a proposal is made that could make it possible to classify fibers according to their toxicologic potential, grading them in accordance with physicochemical parameters, in vitro testing, and animal experiments. This procedure may be applicable to nonvitreous fibers and to organic fibers. PMID- 7882953 TI - Glass fiber manufacturing and fiber safety: the producer's perspective. AB - Historically, the potential health effects of airborne fibers have been associated with the dose, dimension, and durability. Increasing focus is being placed on the latter category. Concern about airborne fiber safety could be reduced by manufacturing fibers that are not respirable; however, due to performance and manufacturing constraints on glasswool insulations, this is not possible today. These products are an important part of today's economy and as a major manufacturer, Owens-Corning is committed to producing and marketing materials that are both safe and effective in their intended use. To this end, manufacturing technology seeks to produce materials that generate low concentrations of airborne fibers, thus minimizing exposure and irritation. The range of fiber diameters is controlled to assure effective product performance and, as far as possible, to minimize respirability. Glass compositions are designed to allow effective fiber forming and ultimate product function. Fiber dissolution is primarily a function of composition; this too, can be controlled within certain constraints. Coupled with these broad parameters is an extensive product stewardship program to assure the safety of these materials. This article will discuss the factors that influence glasswool insulation production, use, and safety. PMID- 7882954 TI - Material-tissue interfaces: the role of surface properties and processes. AB - The introduction of a foreign material into living tissue--intentionally as in biomedical applications (implants, protheses, drugs) or unintentionally as when minerals or fibers are inhaled--results in the creation of interfaces between the material and the surrounding tissue. This article identifies and discusses the possible role of material surface properties and molecular processes occurring at such interfaces. For kinetic and thermodynamic reasons, surfaces are different from the corresponding bulk of the material, and contain reactive (unsaturated) bonds, which in turn lead to the formation of surface reactive layers (e.g., surface oxides on metals) and adsorbed contamination layers. The encounter with the biological environment leads to further surface reactions modifying the surface, and to the adsorption of water, ions, and biomolecules, which are continuously exchanged. The exact nature of the dynamic, adsorbed water, ions, and biomolecule coating in turn influences the behavior of cells approaching the material surface, and hence the tissue response. PMID- 7882955 TI - In vitro assessment of biodurability: acellular systems. AB - The assessment of biodurability of man-made vitreous fibers is essential to the limitation of health hazards associated with human exposure to environments in which respirable fibers are present. In vitro acellular systems provide effective test methods of measuring fiber solubility provided care is taken to select the most suitable solvent and test conditions for the specific fiber type and dimension. PMID- 7882956 TI - In vitro assessment of biopersistence using mammalian cell systems. AB - Biopersistence of fibers in the respiratory airways is a concept including both the physical durability of the fibers and their chemical stability. Physical durability results from several events of diverse origins: fiber epuration by the lung clearance mechanisms, internalization by scavenger cells and fiber splitting. Fibers residing in the lung milieu will be attacked and modified chemically, structurally, and physically (size and shape). Fiber toxicity, which is very likely to be dependent on physical fiber characteristics, will also be dependent on the duration of the fiber's stay in the tissue. Biopersistence, therefore, will be a key issue in determining fiber toxicity. So far, few in vitro systems have been used to study parameters involved in biopersistence. However, examples exist of investigations of fiber phagocytosis by mammalian cells in culture, either by macrophages, or epithelial or mesothelial cells, and studies have also been reported of the fate of internalized fibers in relation to fiber dimensions and chemical stability, especially within macrophages and mesothelial cells. The methods will be presented and discussed to determine to what extent the development of in vitro biophysical models could help in determining those parameters, known or thought to be relevant to fiber persistence. PMID- 7882957 TI - Dual pH durability studies of man-made vitreous fiber (MMVF). AB - Dissolution of fibers in the deep lung may involve both extracellular and intracellular mechanisms. This process was modeled in vitro for each environment using an experimental flow-through system to characterize both total dissolution and specific chemical changes for three representative MMVF's: a glasswool, a slagwool, and a refractory ceramic fiber (RCF). Synthetic physiological fluids at pH 4 and at pH 7.6 were used to simulate macrophage intraphagolysosomal, and extracellular environments, respectively. Actual commercial fiber, sized to rat respirable dimension, having an average fiber diameter of 1 micron and an average length between 15 and 25 microns, was used in the experiments. Fiber dissolution was monitored through change in chemistry of the fluid collected after percolation at a constant rate through a thin bed of sample. There are great differences in total fiber dissolution rates for the different fibers. Slagwool and RCF dissolve more rapidly at pH 4 than at pH 7.6, while the reverse is true for glasswool. Dissolution is sometimes accompanied by a noticeable change in fiber morphology or dimension, and sometimes by no change. There is strong dependency on pH, which affects not only total fiber dissolution, but also the leaching of specific chemical components. This effect is different for each type of fiber, indicating that specific fiber chemistry largely controls whether a fiber dissolves or leaches more rapidly under acidic or neutral conditions. Both total dissolution rates and calculated fiber composition changes are valuable guides to interpreting in vivo behavior of man-made vitreous fibers, and demonstrate the usefulness of in vitro acellular experiments in understanding overall fiber persistence. PMID- 7882958 TI - Durability of ceramic and novel man-made mineral fibers. AB - In vitro solubility testing is an important means of assessing the likely behavior of fibers that are respired and accumulate in the lung. The problem has been that such tests often do not mirror the dissolution and removal mechanisms seen in vivo. Comparison of iron and silica solubility values of various types of mineral fiber showed no obvious correlation. Treating a mineral fiber containing high levels of calcium with normal balanced salt solutions produces a precipitate of calcium phosphate on the fiber surface. This deposit was not seen in fibers isolated from the lung of exposed animals. New solutions have been developed and with variations in the methods of exposing fibers, results similar to those seen in vivo have been obtained. Suitable fluid phases have been examined in static and flow-through systems. The relationship of solubility to biological activity is discussed. PMID- 7882959 TI - Biopersistence of respirable synthetic fibers and minerals: point of view of the chest physician. AB - Problems of diagnosis related to the presence or absence of particles in lung and pleural tissues are discussed from the clinician's viewpoint. The advantage of applying mineralogical analytical techniques is considered. PMID- 7882960 TI - SEM-EDS analysis of glass fibers corroded in physiological solutions by dynamic tests with variable flow rates. AB - The dissolution of mineral fibers has been studied in simulated physiological fluids using a dynamic testing procedure. Fibers of different chemical composition and obtained by different processes with a mean diameter of about 1 micron, have been characterized with respect to their solubility under various test conditions of flow-rate. The surfaces were analyzed using scanning electron microscopy (SEM), energy dispersive spectrometry (EDS) and X-ray diffraction techniques. SEM examinations show the formation of various corrosion patterns: porous, gel-like outer layers; precipitation zones and even, in some cases, no modification of the surface aspect. EDS analyses performed on the fibers, on the fiber surface layers, or on the deposits show three types of chemical composition: areas enriched in Al, in Ca and P, or in Al, Ca, and P. These surface compositions can be found for the same type of fiber tested, depending on the flow rate of the solution. Surface changes depend strongly on the initial composition of the glass and on the test conditions, particularly the flow rate. It is of particular interest to characterize the remaining surfaces (if any) obtained at the end of the in vitro test run and to compare them with surface analysis of the recovered fibers from the in vivo tests to assess the validity of the in vitro tests. PMID- 7882961 TI - Chemical behavior of aluminum and phosphorus during dissolution of glass fibers in physiological saline solutions. AB - The dissolution of textile glass fibers of four different compositions has been investigated at 37 degrees C. In these glasses, which are isolation type, the P2O5 contents scatter between 0 and 2 wt% and Al2O3 from 0.12 to 3.4 wt%. Both static (30-mg fibers; 250-ml solution) and dynamic (50-mg fibers; 40 ml/day flow rate) conditions with or without bubbling of a gas mixture (95:5, N2-CO2) have been used. Two physiological solutions, one proposed by Kanapilly and the other by Scholtze, were used. After each run (1, 3, 7, 14, and sometimes 30, 62 days) the solutions were analyzed for B and Si by inductively coupled plasma (ICP), the weight losses were determined, and the residual solid were observed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Static runs give a better agreement between measured and calculated weight losses from solution analyses than dynamic experiments. SEM examinations indicate diameter reduction and formation of a hydrated Si-rich layer. Sometimes hollow tubes, suggesting the detachment of these layers, are observed. XPS and energy dispersive X-ray (EDX) analysis indicate the formation of a veneer of calcium phosphate for the most rapidly dissolving glass. In other cases an Al increase is observed at the solid solution interface. Whatever experimental conditions are used, the relative dissolution rates of the four glasses are identical. The kinetics may be modeled with variable dissolution rates from initial high values to final low ones. The latter reflect the very low solubility of the residual product. PMID- 7882962 TI - Effect of chemical composition of man-made vitreous fibers on the rate of dissolution in vitro at different pHs. AB - Measurements of rates of dissolution of typical insulation wool fibers (glasswool and basalt based stonewool) and an experimental fiber were made using a flow through equipment. The liquids used were a modified Gamble's solution, adjusted to pH 4.8 and 7.7 +/- 0.2, respectively. The dissolution of SiO2 and CaO was determined over periods of up to three months. The rate of dissolution of stonewool fibers was lower than that of glasswool fibers at pH 7.7, whereas the opposite was true at pH 4.8. The stonewool fibers dissolve congruently, but glasswool fibers tend to dissolve with leaching. The rates of dissolution of fibers of different compositions, including insulation wool (glasswool, basalt based stonewool, slagwool) and experimental fibers were screened using a stationary set-up. Both the chemical composition and pH influenced the rates of dissolution. At pH 7.7 alumina was a determining component and at pH 4.8 the content of SiO2 and CaO was determinant. One experimental fiber with a high content of alumina was an exception having a fairly high rate of dissolution both at pH 4.8 and 7.7. PMID- 7882963 TI - Glass fiber dissolution in simulated lung fluid and measures needed to improve consistency and correspondence to in vivo dissolution. AB - The dissolution of a range of glass fibers including commercial glass and mineral wools has been studied using a modification of Gamble's solution in a flow system at pH 7.4 and 37 degrees C. Dissolution has been followed by weight loss, effluent analysis, and morphology change of fibers and bulk glass. Flow per glass surface area can strongly affect both dissolution rate and morphology due to the effect of the dissolution process on the fluid. Effluent pH is shown to be a guide for choice of optimum flow/area conditions. These conditions provide measurable concentrations of dissolved glass in the effluent while maintaining their concentrations below the point at which they significantly affect the dissolution process. SiO2 and Al2O3 vary widely in the extent to which they are involved in the leaching process, which removes alkalis, alkaline earths, and B2O3. This makes analysis of a single component in the effluent unsuitable as a means of comparing the dissolution rates of a wide range of compositions. PMID- 7882964 TI - In vitro dynamic solubility test: influence of various parameters. AB - This article discusses the dissolution of mineral fibers in simulated physiological fluids (SPF), and the parameters that affect the solubility measurement in a dynamic test where an SPF runs through a cell containing fibers (Scholze and Conradt test). Solutions simulate either the extracellular fluid (pH 7.6) or the intracellular fluid (pH 4.5). The fibers have various chemical compositions and are either continuously drawn or processed as wool. The fiber solubility is determined by the amount of SiO2 (and occasionally other ions) released in the solution. Results are stated as percentage of the initial silica content released or as dissolution rate v in nm/day. The reproducibility of the test is higher with the less soluble fibers (10% solubility), than with highly soluble fibers (20% solubility). The influence of test parameters, including SPF, test duration, and surface area/volume (SA/V), has been studied. The pH and the inorganic buffer salts have a major influence: industrial glasswool composition is soluble at pH 7.6 but not at pH 4.5. The opposite is true for rock- (basalt) wool composition. For slightly soluble fibers, the dissolution rate v remains constant with time, whereas for highly soluble fibers, the dissolution rate decreases rapidly. The dissolution rates believed to occur are v1, initial dissolution rate, and v2, dissolution rate of the residual fibers. The SA of fibers varies with the mass of the fibers tested, or with the fiber diameter at equal mass. Volume, V, is the chosen flow rate. An increase in the SA/V ratio leads to a decrease in the dissolution rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7882965 TI - Phagosomal pH and glass fiber dissolution in cultured nasal epithelial cells and alveolar macrophages: a preliminary study. AB - The dissolution rate of glass fibers has been shown to be pH sensitive using in vitro lung fluid simulant models. The current study investigated whether there is a difference in phagosomal pH (ppH) between rat alveolar macrophages (AM) and rat nasal epithelial cells (RNEC) and whether such a difference would influence the dissolution of glass fibers. The ppH was measured in cultured AM and RNEC using flow cytometric, fluorescence-emission rationing techniques with fluorescein labeled, amorphous silica particles. Glass fiber dissolution was determined in AM and RNEC cultured for 3 weeks with fast dissolving glass fibers (GF-A) or slow dissolving ones (GF-B). The mean diameters of GF-A were 2.7 microns and of GF-B, 2.6 microns, the average length of both fibers was approximately 22 to 25 microns. Dissolution was monitored by measuring the length and diameter of intracellular fibers and estimating the volume, assuming a cylindrical morphology. The ppH of AM was 5.2 to 5.8, and the ppH of RNEC was 7.0 to 7.5. The GF-A dissolved more slowly in RNEC than in AM, and no dissolution was evident in either cell type with GF-B. The volume loss with GF-A after a 3-week culture with AM was 66% compared to 45% for cultured RNEC. These results are different from those obtained using in vitro lung fluid-simulant models where dissolution is faster at higher pH. This difference suggests that dissolution rates of glass fibers in AM should not be applied to the dissolution of fibers in epithelial cells. PMID- 7882966 TI - The 8.5 A projection map of the light-harvesting complex I from Rhodospirillum rubrum reveals a ring composed of 16 subunits. AB - Two-dimensional crystals from light-harvesting complex I (LHC I) of the purple non-sulfur bacterium Rhodospirillum rubrum have been reconstituted from detergent solubilized protein complexes. Frozen-hydrated samples have been analysed by electron microscopy. The crystals diffract beyond 8 A and a projection map was calculated to 8.5 A. The projection map shows 16 subunits in a 116 A diameter ring with a 68 A hole in the centre. These dimensions are sufficient to incorporate a reaction centre in vivo. Within each subunit, density for the alpha and the beta-polypeptide chains is clearly resolved, and the density for the bacteriochlorophylls can be assigned. The experimentally determined structure contradicts models of the LHC I presented so far. PMID- 7882967 TI - Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc. AB - A cDNA encoding a zinc transporter (ZnT-1) was isolated from a rat kidney cDNA expression library by complementation of a mutated, zinc-sensitive BHK cell line. This cDNA was used to isolate the homologous mouse ZnT-1 gene. The proteins predicted for these transporters contain six membrane-spanning domains, a large intracellular loop and a C-terminal tail. ZnT-1 is homologous to zinc and cobalt resistance genes of yeast. Immunocytochemistry with an antibody to a myc epitope added to the C-terminus of ZnT-1 revealed localization to the plasma membrane. Transformation of normal cells with a mutant ZnT-1 lacking the first membrane spanning domain conferred zinc sensitivity on wild-type cells, suggesting that ZnT-1 functions as a multimer. Deletion of the first two membrane-spanning domains resulted in a non-functional molecule, whereas deletion of the C-terminal tail produced a toxic phenotype. Mutant cells have a slightly higher steady-state level of intracellular zinc and high basal expression of a zinc-dependent reporter gene compared with normal cells. Mutant cells have a lower turnover of 65Zn compared with normal cells or mutant cells transformed with ZnT-1. We propose that ZnT-1 transports zinc out of cells and that its absence accounts for the increased sensitivity of mutant cells to zinc toxicity. PMID- 7882968 TI - Aphid transmission of beet western yellows luteovirus requires the minor capsid read-through protein P74. AB - Beet western yellows luteovirus is obligately transmitted by the aphid Myzus persicae in a circulative, non-propagative fashion. Virus movement across the epithelial cells of the digestive tube into the hemocoel and from the hemocoel into the accessory salivary glands is believed to occur by receptor-mediated endocytosis and exocytosis. Virions contain two types of protein; the major 22 kDa capsid protein and the minor read-through protein, P74, which is composed of the major capsid protein fused by translational read-through to a long C-terminal extension called the read-through domain. Beet western yellows virus carrying various mutations in the read-through domain was tested for its ability to be transmitted to test plants by aphids fed on agro-infected plants and semi purified or purified virus preparations. The results establish that the read through domain carries determinants that are essential for aphid transmission. The findings also reveal that the read-through domain is important for accumulation of the virus in agro-infected plants. PMID- 7882969 TI - Inhibition of flower formation by antisense repression of mitochondrial citrate synthase in transgenic potato plants leads to a specific disintegration of the ovary tissues of flowers. AB - The tricarboxylic acid (TCA) cycle constitutes a major component of the mitochondrial metabolism of eucaryotes, including higher plants. To analyze the importance of this pathway, we down-regulated mitochondrial citrate synthase (mCS; EC 4.1.3.7), the first enzyme of the TCA cycle, in transgenic potato plants using an antisense RNA approach. Several transformants were identified with reduced citrate synthase activity (down to approximately 6% of wild-type activity). These plants were indistinguishable from wild-type plants in the greenhouse during vegetative growth. A major change, however, was seen upon initiation of the generative phase (flower formation). In the case of transgenic plants with a strong reduction in citrate synthase activity (< 30% of wild-type levels), flower buds formed > 2 weeks later as compared with wild-type plants. Furthermore, flower buds from these plants did not develop into mature flowers but rather were aborted at an early stage of development. Microscopic analysis showed that in these cases ovaries disintegrated during flower development. We conclude that the TCA cycle is of major importance during the transition from the vegetative to the generative phase. PMID- 7882970 TI - Chemotaxis and phototaxis require a CheA histidine kinase in the archaeon Halobacterium salinarium. AB - Histidine kinases are part of the two-component signal transduction system responsible for eubacterial responses to diverse environmental signals. They have recently been detected in eukaryotes but their existence in the kingdom Archaea remains uncertain. Here we report the sequence and function of a histidine kinase (CheAH.s.) from Halobacterium salinarium, the first such transmitter in Archaea. The protein CheAH.s. (668 residues) has significant sequence identity with the CheA proteins known from eubacterial signal transduction (e.g. 34% identity with CheA from Bacillus subtilis). Antibodies were raised against CheAH.s. as expressed in Escherichia coli and were used in Western blotting to demonstrate the expression of cheAH.s. in H. salinarium. As has been observed for other halophilic proteins, CheAH.s. has a deviant electrophoretic migration, with an apparent molecular weight of 103 kDa on SDS-PAGE compared with a calculated molecular weight of 72 kDa. Deletion of a part of the cheAH.s. gene leads to loss of both chemotactic and phototactic responses in H. salinarium as measured by swarm plate assays, motion analysis and tethering experiments. This indicates that CheAH.s. plays a crucial role in chemical and light signal integration, presumably interacting with at least two phototransducers and a number of chemoreceptors. PMID- 7882971 TI - Requirement of MAP kinase for differentiation of fibroblasts to adipocytes, for insulin activation of p90 S6 kinase and for insulin or serum stimulation of DNA synthesis. AB - A phosphorothioate-oligonucleotide-based antisense strategy for depleting MAP kinase was developed. The 17mer antisense probe, EAS 1, caused a potent and concentration-dependent decrease in the steady state expression of p42 and p44 MAP kinase in 3T3 L1 fibroblasts and adipocytes with submicromolar concentrations effective. Antisense EAS 1 elicited a dose-dependent inhibition of insulin- and serum-stimulated DNA synthesis. Elimination of p42 MAP kinase by > 95% and p44 MAP kinase to levels undetected blocked the ability of serum in 3T3 L1 fibroblasts and insulin in 3T3 L1 adipocytes to stimulate DNA synthesis by 87 95%. The differentiation of 3T3 L1 fibroblasts into adipocytes was prevented by 1 microM antisense EAS 1. The corresponding sense, scrambled or sense plus antisense EAS 1 phosphorothioate oligonucleotides did not deplete the p42 or p44 MAP kinase from either cell type, did not inhibit stimulation of DNA synthesis and did not interfere with differentiation. Two kinases on different MAP kinase activation pathways were not depleted by antisense EAS 1 whereas the ability of insulin to activate p90 S6 kinase was > 90% eliminated in 3T3 L1 adipocytes by 4.5 microM antisense EAS 1. In conclusion these results show that MAP kinase is required for insulin and serum stimulation of DNA synthesis, for insulin stimulation of p90 S6 kinase activity and for differentiation of 3T3 L1 cells. Moreover, the development of the antisense probe EAS 1 against a target sequence of p42 MAP kinase that is conserved in p44 MAP kinase and across a range of species provides a molecular tool of general applicability for further dissecting the precise targets and roles of MAP kinase. PMID- 7882972 TI - Regulation of Raf-1 kinase activity by the 14-3-3 family of proteins. AB - We have identified the beta (beta) isoform of the 14-3-3 family of proteins as an activator of the Raf-1 protein kinase. 14-3-3 was isolated in a yeast two-hybrid screen for Raf-1 kinase domain binding proteins. Purified bovine brain 14-3-3 interacted specifically with both c-Raf-1 and the isolated Raf-1 kinase domain. Association was sensitive to the activation status of Raf-1; 14-3-3 bound to unactivated Raf-1, but not Raf-1 activated by protein kinase C alpha or Ras and Lck. The significance of these interactions under physiological conditions was demonstrated by co-immunoprecipitation of Raf-1 and 14-3-3 from extracts of quiescent, but not mitogen-stimulated, NIH 3T3 cells. 14-3-3 was not a preferred Raf-1 substrate in vitro and did not significantly affect Raf-1 kinase activity in a purified system. However, in cell-free extracts 14-3-3 acted as a Ras independent activator of both c-Raf-1 and the Raf-1 kinase domain. The same results were obtained in vivo using transfection assays; 14-3-3 enhanced both c Raf-1- and Raf-1 kinase domain-stimulated expression of AP-1- and NF-kappa B dependent reporter genes and accelerated Raf-1 kinase domain-triggered differentiation of PC12 cells. We conclude that 14-3-3 is a latent co-activator bound to unactivated Raf-1 in quiescent cells and mediates mitogen-triggered but Ras-independent regulatory effects aimed directly at the kinase domain. PMID- 7882973 TI - A novel type of myosin implicated in signalling by rho family GTPases. AB - A novel widely expressed type of myosin (fifth unconventional myosin from rat: myr 5) from rat tissues, defining a ninth class of myosins, was identified. The predicted amino acid sequence of myr 5 exhibits several features not found previously in myosins. The myosin head domain contains a unique N-terminal extension and an insertion of 120 amino acids at a postulated myosin-actin contact site. Nevertheless, myr 5 is able to bind actin filaments in an ATP regulated manner. The head domain is followed by four putative light chain binding sites. The tail domain of myr 5 contains a region which coordinates two atoms of zinc followed by a region that stimulates GTP hydrolysis of members of the ras-related rho subfamily of small G-proteins. Myr 5 therefore provides the first direct link between rho GTPases which have been implicated in the regulation of actin organization and the actin cytoskeleton. It is also the first unconventional myosin for which a tail binding partner(s), namely members of the rho family, has been identified. PMID- 7882974 TI - Co-activation of RanGTPase and inhibition of GTP dissociation by Ran-GTP binding protein RanBP1. AB - RCC1 (the regulator of chromosome condensation) stimulates guanine nucleotide dissociation on the Ras-related nuclear protein Ran. Both polypeptides are components of a regulatory pathway that has been implicated in regulating DNA replication, onset of and exit from mitosis, mRNA processing and transport, and import of proteins into the nucleus. In a search for further members of the RCC1 Ran signal pathway, we have identified proteins of 23, 45 and 300 kDa which tightly bind to Ran-GTP but not Ran-GDP. The purified soluble 23 kDa Ran binding protein RanBP1 does not activate RanGTPase, but increases GTP hydrolysis induced by the RanGTPase-activating protein RanGAP1 by an order of magnitude. In the absence of RanGAP, it strongly inhibits RCC1-induced exchange of Ran-bound GTP. In addition, it forms a stable complex with nucleotide-free RCC1-Ran. With these properties, it differs markedly from guanine diphosphate dissociation inhibitors which preferentially prevent the exchange of protein-bound GDP and in some cases were shown to inhibit GAP-induced GTP hydrolysis. RanBP1 is the first member of a new class of proteins regulating the binding and hydrolysis of GTP by Ras-related proteins. PMID- 7882976 TI - Two amino acids, located in transmembrane domains VI and VII, determine the selectivity of the peptide agonist SMS 201-995 for the SSTR2 somatostatin receptor. AB - Human somatostatin receptor subtypes (SSTR1-5) bind their natural ligands SRIF-14 and SRIF-28 with high affinity. By contrast, short synthetic SRIF analogues such as SMS 201-995, a peptide agonist used for the treatment of various endocrine and malignant disorders, display sub-nanomolar affinity only for the receptor subtype SSTR2. To understand the molecular nature of selective peptide agonist binding to somatostatin receptors we have now, by site-directed mutagenesis, identified amino acids mediating SMS 201-995 specificity for SSTR2. Sequentially, amino acids in SSTR1, a receptor subtype exhibiting low affinity for SMS 201-995, were exchanged for the corresponding SSTR2 residues. After three consecutive steps, in which eight amino acids were exchanged, a SSTR1 mutant receptor with high affinity for SMS 201-995 was obtained. Receptor mutants with different combinations of these eight amino acids were then constructed. A single Ser305 to Phe mutation in TM VII increased the affinity of SSTR1 for SMS 201-995 nearly 100 fold. When this mutation was combined with an exchange of Gln291 to Asn in TM VI, almost full susceptibility to SMS 201-995 was obtained. Thus, it is concluded that the specificity of SMS 201-995 for SSTR2 is mainly defined by these two amino acids in transmembrane domains VI and VII. Using the conjugate gradient method we have, by analogy to the well established structure of bacteriorhodopsin, built a model for SRIF receptor-ligand interactions that explains the importance of Gln291 and Ser305 for the selectivity of agonists. PMID- 7882975 TI - Ecdysone regulation of the Drosophila Sgs-4 gene is mediated by the synergistic action of ecdysone receptor and SEBP 3. AB - The steroid hormone 20-hydroxyecdysone controls both induction and repression of the Drosophila 'intermolt gene' Sgs-4. We show here that the ecdysone receptor binds to two sites, element I and element II, in the regulatory region of Sgs-4. A functional analysis revealed that element II appears to be of no importance for Sgs-4 expression, while element I proved to be an ecdysone response element that is necessary, but not sufficient, for induction of Sgs-4 expression. Our results provide no evidence that repression of Sgs-4 expression is mediated by one of the two receptor binding sites. In the close vicinity of elements I and II, we detected two binding sites of secretion enhancer binding protein 3 (SEBP 3). Like receptor element I, one of these sites also proved to be necessary, but not sufficient, for expression of Sgs-4. Therefore, induction of Sgs-4 requires binding of both ecdysone receptor and SEBP 3 to a complex hormone response unit, which also contains binding sites for a third factor, SEBP 2. The SEBP 2 sites coincide with binding sites of products of the Broad-Complex locus, which has been implicated recently with transduction of the hormonal signal. Thus, the available data suggest that induction of Sgs-4, and possibly other 'intermolt genes', is a combination of a primary and a secondary response to the hormone. PMID- 7882977 TI - TGF-beta superfamily members promote survival of midbrain dopaminergic neurons and protect them against MPP+ toxicity. AB - The superfamily of transforming growth factors-beta (TGF-beta) comprises an expanding list of multifunctional proteins serving as regulators of cell proliferation and differentiation. Prominent members of this family include the TGF-beta s 1-5, activins, bone morphogenetic proteins and a recently discovered glial cell line-derived neurotrophic factor (GDNF). In the present study we demonstrate and compare the survival promoting and neuroprotective effects of TGF beta 1, -2 and -3, activin A and GDNF for midbrain dopaminergic neurons in vitro. All proteins increase the survival of tyrosine hydroxylase-immunoreactive dopaminergic neurons isolated from the embryonic day (E) 14 rat mesencephalon floor to varying extents (TGF-beta s 2.5-fold, activin A and GDNF 1.6-fold). TGF beta s, activin A and GDNF did not augment numbers of very rarely observed astroglial cells visualized by using antibodies to glial fibrillary acidic protein and had no effect on cell proliferation monitored by incorporation of BrdU. TGF-beta 1 and activin A protected dopaminergic neurons against N-methyl-4 phenylpiridinium ion toxicity. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that TGF-beta 2 mRNA, but not GDNF mRNA, is expressed in the E14 rat midbrain floor and in mesencephalic cultures. We conclude that TGF beta s 1-3, activin A and GDNF share a neurotrophic capacity for developing dopaminergic neurons, which is not mediated by astroglial cells and not accompanied by an increase in cell proliferation. PMID- 7882978 TI - Contrasting roles for c-Myc and L-Myc in the regulation of cellular growth and differentiation in vivo. AB - Although myc family genes are differentially expressed during development, their expression frequently overlaps, suggesting that they may serve both distinct and common biological functions. In addition, alterations in their expression occur at major developmental transitions in many cell lineages. For example, during mouse lens maturation, the growth arrest and differentiation of epithelial cells into lens fiber cells is associated with a decrease in L- and c-myc expression and a reciprocal rise in N-myc levels. To determine whether the down-regulation of L- and c-myc are required for mitotic arrest and/or completion of differentiation and whether these genes have distinct or similar activities in the same cell type, we have studied the consequences of forced L- and c-myc expression in the lens fiber cell compartment using the alpha A-crystallin promoter in transgenic mice (alpha A/L-myc and alpha A/c-myc mice). With respect to morphological and molecular differentiation, alpha A/L-myc lenses were characterized by a severely disorganized lens fiber cell compartment and a significant decrease in the expression of a late-stage differentiation marker (MIP26); in contrast, differentiation appeared to be unaffected in alpha A/c-myc mice. Furthermore, an analysis of proliferation indicated that while alpha A/L myc fiber cells withdrew properly from the cell cycle, inappropriate cell cycle progression occurred in the lens fiber cell compartment of alpha A/c-myc mice. These observations indicate that continued late-stage expression of L-myc affected differentiation processes directly, rather than indirectly through deregulated growth control, whereas constitutive c-myc expression inhibited proliferative arrest, but did not appear to disturb differentiation. As a direct corollary, our data indicate that L-Myc and c-Myc are involved in distinct physiological processes in the same cell type. PMID- 7882979 TI - Nuclear translocation of a maternal CCAAT factor at the start of gastrulation activates Xenopus GATA-2 transcription. AB - The transcription factor GATA-2 is present in blood cell precursors and plays a pivotal role in the control of erythroid differentiation. In Xenopus embryos, low levels of GATA-2 mRNA are maternally derived, while the onset of zygotic GATA-2 expression coincides with commitment to haematopoietic lineages. However, its initial transcriptional activation is not restricted to the presumptive blood islands, but occurs throughout ventral and lateral regions, in all three germ layers. In order to determine how this expression pattern is controlled, we have isolated and characterized the Xenopus GATA-2 gene. We show that 1.65 kb of 5' flanking sequences are sufficient to direct both correct transcriptional initiation in oocytes and appropriate temporal and spatial gene expression in early embryos. The transgene is activated during gastrulation and by neurula stages in predominantly expressed in the ventral hemisphere. We demonstrate that a CCAAT element is necessary for gene activity in both systems and that extracts prepared from oocytes and embryos contain a factor which specifically recognizes this element. We also show that cytoplasmic localization inhibits the function of this CCAAT factor until the beginning of gastrulation, when the zygotic GATA-2 gene is activated. These observations extend our understanding of the mechanisms by which maternal factors control the temporal activation of transcription in early vertebrate embryos. PMID- 7882980 TI - Levels of homeotic protein function can determine developmental identity: evidence from low-level expression of the Drosophila homeotic gene proboscipedia under Hsp70 control. AB - The autonomous selector capacity of the homeotic proboscipedia (pb) gnee of the Drosophila Antennapedia Complex was tested. We introduced into the germline a P element containing a transcriptional fusion of a mini-gene for pb (normally required for formation of the labial and maxillary palps of the mouthparts) and the Hsp70 promoter. Uninduced expression of this Hsp70:pb element (HSPB) directs a novel, fully penetrant dominant transformation of antennae toward maxillary palps. Gene dosage experiments varying the number of HSPB elements indicate that the extent of the dominant transformation depends on the level of PB protein. At the same time, expression from the transgene also rescues recessive pb mutations. Finally, HSPB function may override the dominant antennal transformations caused by Antennapedia (Antp) mutations in a dose-sensitive manner, directing a switch of the antennal disc-derived appendage from ectopic leg to ectopic maxillary palp. This switch correlated with strikingly reduced ANTP protein accumulation when PB concentrations exceeded a genetically defined threshold level. These observations support a crucial role for quantitative aspects of pb function in determining segmental identity, including cross-regulatory events involved in this determination. PMID- 7882981 TI - The Aspergillus PacC zinc finger transcription factor mediates regulation of both acid- and alkaline-expressed genes by ambient pH. AB - The pH regulation of gene expression in Aspergillus nidulans is mediated by pacC, whose 678 residue-derived protein contains three putative Cys2His2 zinc fingers. Ten pacCc mutations mimicking growth at alkaline pH remove between 100 and 214 C terminal residues, including a highly acidic region containing an acidic glutamine repeat. Nine pacC+/- mutations mimicking acidic growth conditions remove between 299 and 505 C-terminal residues. Deletion of the entire pacC coding region mimics acidity but leads additionally to poor growth and conidiation. A PacC fusion protein binds DNA with the core consensus GCCARG. At alkaline ambient pH, PacC activates transcription of alkaline-expressed genes (including pacC itself) and represses transcription of acid-expressed genes. pacCc mutations obviate the need for pH signal transduction. PMID- 7882983 TI - GATA1 and YY1 are developmental repressors of the human epsilon-globin gene. AB - The human epsilon-globin gene is transcribed in erythroid cells only during the embryonic stages of development. Expression of epsilon-globin gene, however, can be maintained in adult transgenic mice following removal of DNA positioned between -467 and -182 bp upstream of the epsilon-globin cap site. We have identified three protein binding regions within this silencer; a CCACC motif around -379, two overlapping motifs for YY1 and GATA around -269 and a GATA motif around -208 and we have analyzed their function during development by studying several mutants in transgenic mice. Mutation of the -208 GATA motif allows high epsilon-globin transgene expression in the adult suggesting that, in addition to its positive effects on transcription, GATA-1 also plays a negative role in the regulation of globin gene expression during development. Repression of epsilon gene expression in the adult also requires a functional YY1 binding site at position -269. Finally, mutation of the -379 CCACC site results in a small but detectable level of epsilon expression in adult erythroid cells. Thus, multiple proteins, including GATA-1, participate in the formation of the epsilon gene repressor complex that may disrupt the interaction between the proximal epsilon promoter and the locus control region (LCR) in definitive erythroid cells. PMID- 7882982 TI - Purification of the sequence-specific transcription factor CTCBF, involved in the control of human collagen IV genes: subunits with homology to Ku antigen. AB - The common promoter region of the human collagen type IV genes COL4A1 and COL4A2 comprises a C5TC7 sequence ('CTC box') which is specifically recognized by the recently identified transcription factor CTC box binding factor (CTCBF) involved in the control of divergent transcription of the two genes. This factor has now been purified by affinity chromatography on heparin-agarose and CTC-Sepharose. The CTCBF contains two subunits, CTC75 and CTC85, with molecular weights of 75 and 85 kDa, respectively. Sequence analysis of LysC-derived peptides of the two subunits revealed identity or close homology to p70 and p80 subunits of the human autoantigen Ku. The sequence-specific binding CTCBF represents a presumably tetrameric complex composed of two CTC75/85 heterodimers with an apparent molecular weight of 360-400 kDa. UV crosslinking experiments, the use of Ku specific antibodies in gel retardation assays and immunoblotting proved that both subunits are involved in sequence-specific interaction with the CTC box motif. The tetrameric complex dissociates in a concentration-dependent manner to CTC75/85 heterodimers which now bind sequence independently to DNA. Three lines of evidence indicate that TATA binding protein (TBP) is additionally involved in the formation of CTCBF: (i) TBP can be detected in purified CTCBF; (ii) the addition of recombinant TBP stimulates formation of the CTCBF-DNA complex; and (iii) antibodies directed against TBP interfere strongly with the formation of the specific protein-DNA complex. The results presented support the idea that the subunits CTC75 and CTC85 (identical or homologous to p70 and p80 of the Ku antigen) are integral parts of CTCBF, and give a first indication of the importance of TBP in the formation of CTCBF. PMID- 7882984 TI - The requirement for the basal transcription factor IIE is determined by the helical stability of promoter DNA. AB - The role of the basal transcription factor TFIIE was investigated in RNA polymerase II transcription reactions reconstituted with purified proteins. Using negatively supercoiled templates, which circumvent the requirement for TFIIH, we observed that transcription from the adenovirus major-late (ML) core promoter is more dependent on TFIIE than transcription from the adenovirus E4 (E4) or mouse mammary tumor virus (MMTV) promoters. For all three promoters, an increase in the ionic strength of the reaction mixtures led to an increased dependence on TFIIE. Analysis of hybrid ML/MMTV promoters showed that the region encompassing the start site, from -10 to +10, dictates this dependence. Transcription from a relaxed E4 template with a pre-melted -8 to +2 region was completely independent of both TFIIE and TFIIH. We propose that on negatively supercoiled templates TFIIE can facilitate promoter melting. PMID- 7882985 TI - Evidence for a Prp24 binding site in U6 snRNA and in a putative intermediate in the annealing of U6 and U4 snRNAs. AB - A mutation (U4-G14C) that destabilizes the base-pairing interaction between U4 and U6 snRNAs causes the accumulation of a novel complex containing U4, U6 and Prp24, a protein with RNA binding motifs. An analysis of suppressors of this cold sensitive mutant led to the hypothesis that this complex is normally a transient intermediate in the annealing of U4 and U6. It was proposed that Prp24 must be released to form a fully base-paired U4/U6 snRNP. By using a chemical probing method we have tested the prediction that nucleotides A40-C43 in U6 mediate the binding of Prp24. Consistent with the location of recessive suppressors in U6, we find that residues A40-C43 are protected from chemical modification in U4/U6 complexes from the U4-G14C mutant but not from the wild-type or suppressor strains carrying mutations in U6 or PRP24. Furthermore, we find that base-pairing is substantially disrupted in the mutant complexes. Notably, the base-paired structure is restored in recessive suppressors despite the presence of a mismatched base-pair at the U4-G14C site. Our results support the model that Prp24 binds to U6 to promote its association with U4, but must dissociate to allow complete annealing. PMID- 7882986 TI - Structural and functional studies of retroviral RNA pseudoknots involved in ribosomal frameshifting: nucleotides at the junction of the two stems are important for efficient ribosomal frameshifting. AB - Ribosomal frameshifting, a translational mechanism used during retroviral replication, involves a directed change in reading frame at a specific site at a defined frequency. Such programmed frameshifting at the mouse mammary tumor virus (MMTV) gag-pro shift site requires two mRNA signals: a heptanucleotide shifty sequence and a pseudoknot structure positioned downstream. Using in vitro translation assays and enzymatic and chemical probes for RNA structure, we have defined features of the pseudoknot that promote efficient frameshifting. Heterologous RNA structures, e.g. a hairpin, a tRNA or a synthetic pseudoknot, substituted downstream of the shifty site fail to promote frameshifting, suggesting that specific features of the MMTV pseudoknot are important for function. Site-directed mutations of the MMTV pseudoknot indicate that the pseudoknot junction, including an unpaired adenine nucleotide between the two stems, provides a specific structural determinant for efficient frameshifting. Pseudoknots derived from other retroviruses (i.e. the feline immunodeficiency virus and the simian retrovirus type 1) also promote frameshifting at the MMTV gag-pro shift site, dependent on the same structure at the junction of the two stems. PMID- 7882987 TI - Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. PMID- 7882988 TI - T-cell antigen receptor-induced signal-transduction pathways--activation and function of protein kinases C in T lymphocytes. AB - CONTENTS. T-cell activation--Structure of the T-cell antigen receptor--Modular organisation of the T-cell antigen receptor--T-cell antigen receptor-coupled signaling pathways: Activation of protein-tyrosine kinase by the T-cell antigen receptor; Signal transduction in lymphoid cells involves several protein-tyrosine kinases in parallel; Regulation of T-cell antigen receptor signaling by the phosphoprotein phosphatase CD45--Consequences of T-cell antigen receptor-induced tyrosine phosphorylation: Activation of phosphoinositol-lipid-turnover pathways- Activation of phospholipase C-gamma-1: p59fyn or p56lck?--G-protein motif of CD3 gamma: relevance for signal transduction--Association of lipid kinase with the T cell antigen receptor--Intracellular signaling by phospholipid metabolites and calcium: activation of protein kinase C--Protein kinase C isoenzymes- Heterogenity of protein kinase C and mode of activation--Phospholipid-derived mediators in activation of protein kinase C in T-cells--Role of phospholipase D metabolites in activation of protein kinase C--Polyunsaturated fatty acids and lysophosphatidylcholine as activators of protein kinase C--Potein kinase C and p21ras function in interdependent and distinct signaling pathways during T-cell activation--Raf-1 kinase: regulator or target of protein kinase C?--Summary and perspectives. PMID- 7882989 TI - Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors. AB - The coupling of two endothelin receptor subtypes (ET(A) and ETB) to several types of guanine-nucleotide-binding regulatory protein (G protein) was examined. Two subtypes of receptor cDNAs were transfected alone or together with four different G protein alpha subunit cDNAs in COS-7 cells. In ET(A) receptor-transfected cells, endothelin-1 (ET-1) activated phosphatidylinositol-specific phospholipase C as measured by the production of phosphatidylinositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. ETB-receptor-transfected cells also produced Ins(1,4,5)P3 on stimulation by ET-1. The ET-1-induced production of Ins(1,4,5)P3 was markedly higher in G alpha q-cotransfected or G alpha 11-cotransfected cells than in cells transfected with each receptor alone. ET-1 also stimulated production of cAMP in ET(A) or ETB receptor-transfected cells. The production of cAMP was synergistically amplified by G alpha s co-transfection with each receptor. In contrast, when G alpha i2 was co-transfected with the ET(A) or ETB receptor, ET-1 displayed an inhibitory action on forskolin-stimulated cAMP accumulation. Pertussis-toxin treatment of the G alpha i2-transfected cells resulted in abolition of the endothelin-induced inhibition of cAMP accumulation. These observations indicate that both ET(A) and ETB receptors are able to couple to Gq, G11, Gs and Gi2, and suggest that endothelin receptors stimulate multiple effectors via several types of G protein simultaneously. The overall effects induced by endothelin may differ in cell types depending on the level of expression of each G-protein subtype in the cell. PMID- 7882990 TI - Synthesis of a new photoaffinity probe, 5-azido-[32P]UDPxylose, by UDPglucuronate carboxylyase from wheat germ. AB - The enzyme, UDPglucuronic acid carboxylase (EC 4.1.1.35), was extensively purified from wheat germ, and was used to convert 5-azido-[32P]UDPglucuronic acid to 5-azido-[32P]UDPxylose, for use as a new photoaffinity probe. The carboxylyase was purified approximately 1200-fold using conventional methods, and the enzyme preparation, at the final stage of purification, was stable to storage at -20 degrees C for at least 9 months with little or no loss of activity. The partially purified carboxylyase catalyzed the conversion of 5-azido-[32P]UDPglucuronic acid to 5-azido-[32P]UDPxylose in good yield, and the UDPxylose probe was purified by ion-exchange chromatography, and characterized. The newly synthesized photoaffinity analog, 5-azido-[32P]UDPxylose, should be a valuable tool in the purification of various xylosyltransferases. PMID- 7882991 TI - Direct cardiolipin assay in yeast using the red fluorescence emission of 10-N nonyl acridine orange. AB - The dye 10-N-nonyl-3,6-bis(dimethylamino)acridine (10-N-nonyl acridine orange) has been recently identified as a specific probe for cardiolipin (Ka = 2 x 10(6) M-1). It also interacts, at lower affinity (Ka = 7 x 10(4) M-1), with other acidic phospholipids [Petit, J. M., Maftah, A., Ratinaud, M. H. & Julien, R. (1992) Eur. J. Biochem. 209, 267-273]. In order to reduce the interference corresponding to monoacidic phospholipid binding, we have quantified cardiolipin by using a fluorimetric method based on the red fluorescence of the dye dimers formed at the diacidic phospholipid contact. Hence we have demonstrated that: (a) in yeast, the mitochondrion is the target of the dye whatever the cell metabolism; (b) membrane or protein organization and fatty acid unsaturation do not significantly modify the binding of 10-N-nonyl acridine orange. Using thin walled vesicles, a linear relationship was established between the amount of cardiolipin and the red fluorescence emitted by the dye. Low red fluorescences were also observed with vesicles containing phosphatidylserine and phosphatidylinositol. However, at the same acidic phospholipid concentration, the fluorescence was much higher using cardiolipin-containing vesicles (fivefold that observed with phosphatidylserine-containing vesicles). Thus, 10-N-nonyl acridine orange was applied to cardiolipin quantification in yeast. This new method revealed that cells growing with a high glucose concentration contained 2.2 +/- 0.3 nmol cardiolipin/10(6) cells, whereas with lactate they contained about twice this amount (3.9 +/- 0.3 nmol cardiolipin). PMID- 7882992 TI - Cloning and expression of the mouse laminin gamma 2 (B2t) chain, a subunit of epithelial cell laminin. AB - We have isolated and sequenced the full-length cDNA for the mouse laminin gamma 2 chain and mapped it to mouse Chromosome 1 proximal to laminin gamma 1. The mRNA for the mouse gamma 2 spans 5.2 kb and codes for a 1192-residue amino acid polypeptide. The gamma 2 chain (formerly termed laminin B2t), a homologue of gamma 1 (formerly B2), lacks an N-terminal domain and has a shorter domain III in comparison to the laminin gamma 1 chain. The expression of the laminin gamma 2 and gamma 1 chains in both newborn and fetal mice was examined by both Northern analysis and in situ hybridization. mRNA for the laminin gamma 2 chain was expressed specifically by epithelial cells in many tissues with a particularly high level of expression in the tongue, hair follicles, lung and kidney. In contrast, a high level of expression of the laminin gamma 1 chain mRNA was seen in both epithelial and endothelial cells in these tissues. In addition, gamma 1 mRNA was expressed in other tissues such as the nasal septum, blood vessels, and the muscle of the tongue. Immunohistochemistry with an anti-gamma 2 IgG detected strong expression of the laminin gamma 2 chain in the basement membrane of the collecting tubules of the kidney and of the pancreas. Immunoprecipitation studies with antibodies to the gamma 2 chain detected three species at 165, 155 and 140 kDa in HT-1080 cell-conditioned media. This protein complex is characteristic of the kalinin (nicein/epiligrin) complex, and provides further evidence that these proteins are identical and that the gamma 2 chain is the subunit of the epithelial-cell-specific laminin. PMID- 7882993 TI - Complementary DNAs for two arylamine N-acetyltransferases with identical 5' non coding regions from rat pineal gland. AB - A cDNA library was constructed from the pineal gland of rats injected with isoproterenol and screened with 32P-labeled cDNAs encoding arylamine N acetyltransferases from rabbit and human liver. Two types of cDNAs for arylamine N-acetyltransferases (A-type and B-type) were isolated. Expression of the cDNAs in Chinese hamster ovary cells indicated that A-type N-acetyltransferase acetylates both arylamines and arylalkylamines, while the B-type enzyme acetylates only arylamines. Therefore, neither the A-type nor the B-type of enzyme seems to be the arylalkylamine N-acetyltransferase involved in melatonin synthesis in the pineal gland. Nucleotide sequence analysis revealed that both A type and B-type cDNAs code for 290 amino acids, and that they showed 82.8% similarity in the coding region. However, the nucleotide sequence in the 5' non coding region was identical in the A-type and B-type cDNAs. In addition, the 5' non-coding region contained another possible open reading frame for 79 amino acids. Data base research revealed that the complementary sequence of the 5' non coding region has high similarity with the coding regions of cDNAs for high mobility-group proteins (HMG) 1 and 2, which are thought to regulate mRNA transcription. PMID- 7882994 TI - Isolation of the catalytic subunit of a membrane-bound H(+)-pyrophosphatase from pea stem mitochondria. AB - The catalytic subunit of a membrane-bound pyrophosphatase was purified by electroendosmotic preparative electrophoresis from etiolated pea stem mitochondria. The enzyme was identified as a single peak relatively pure, because only a very limited number of polypeptides were detectable by SDS/PAGE of the active fractions. The pyrophosphatase was associated to a band with a molecular mass of 35 kDa, showing a specific activity of 0.7 mumol Pi . mg-1 protein . min 1 (37 degrees C, pH 8.0) and an apparent Km value of 200 microM. The hydrolytic activity required Mg2+, was inhibited by imidodiphosphate (HNO6P2Na4), Ca2+, F- and was stimulated by phospholipids. Cardiolipin, phophatidylcholine and phosphatidylethanolamine had the maximal activating effect. The isolated protein is very similar to the catalytic subunit of pyrophosphatases isolated from rat liver (beta-subunit) and Saccharomyces cerevisiae mitochondria. PMID- 7882995 TI - Immunochemical determination of human cholesterol 7 alpha-hydroxylase. AB - To produce antibodies for determination of the protein mass of human cholesterol 7 alpha-hydroxylase, a fusion protein was prepared from an in-frame fusion gene containing the cDNA for human cholesterol 7 alpha-hydroxylase near the 3' terminus of the lacZ gene of Escherichia coli. The fusion protein was purified by (NH4)2SO4 fractionation and gel-filtration chromatography on a Sephacryl column. Rabbits were immunized with this fusion protein and antisera were obtained. IgG was prepared by submitting antisera to chromatography on protein-A--Sepharose. Antibodies directed against bacterial proteins including beta-galactosidase were removed by affinity chromatography on a column to which bacterial proteins of E. coli containing beta-galactosidase had been immobilized. Evidence that the antibodies are indeed reactive against human liver cholesterol 7 alpha hydroxylase was obtained by immunoblot analysis with human cholesterol 7 alpha hydroxylase expressed in COS cells from the coding region of the human cholesterol 7 alpha-hydroxylase cDNA. The antiserum inhibited the activity of cholesterol 7 alpha-hydroxylase in human liver microsomes by approximately 70%. On immunoblotting of solubilized human liver microsomes, a positive band was obtained at a position corresponding to the protein mass for human cholesterol 7 alpha-hydroxylase. When calibration was performed using the fusion protein, a linear relationship was observed between the density and the amount of protein. Proportionality was also observed between the density and the amount of protein for microsomes of COS cells transfected with the coding region of the human cholesterol 7 alpha-hydroxylase cDNA. Liver microsomes from patients treated with cholestyramine (n = 3) were shown to contain levels of cholesterol 7 alpha hydroxylase protein approximately twofold higher than those of liver microsomes from untreated patients (n = 6; P < 0.02), whereas cholesterol 7 alpha hydroxylase activity was approximately six-fold higher in liver microsomes from the cholestyramine-treated patients than in the corresponding preparations from the untreated patients (P < 0.02). The higher activities observed in cholestyramine-treated patients, therefore, cannot be explained only by an increased amount of protein, suggesting a posttranslational mechanism to increase the activity of human cholesterol 7 alpha-hydroxylase in addition to the transcriptional control. PMID- 7882996 TI - Secondary structure of RecA in solution. The effects of cofactor, DNA and ionic conditions. AB - The interactions of RecA with double-stranded DNA and with cofactor adenosine 5' [3-thio]triphosphate (ATP[S] an analog of ATP) have been characterized by circular dichroism (CD) spectroscopy in a search for conformational changes associated with the formation of helical RecA . ATP . DNA fibers. Upon interaction with the RecA protein the cofactor is found to be structurally perturbed, possibly towards the syn ribose form of ATP[S], while the secondary structure of RecA remains unaffected. By contrast, when the ATP[S] . RecA . DNA complex is formed, a distinct change of the protein CD spectrum near 200 nm is observed as a result of interaction of RecA with DNA. The main change occurs upon the binding of the first DNA molecule [RecA can bind up to three DNA molecules simultaneously; Takahashi, M., Kubista, M. & Norden, B. (1991) Biochimie (Paris) 73, 219-226] and the effect appears to be independent of DNA sequence, suggesting a general change of protein conformation upon DNA binding. The CD of DNA is changed, indicating an alteration of the DNA structure, possibly related to stretching and unwinding. A small, reversible, decrease in the CD amplitude of RecA was observed when raising the temperature from 4 degrees C to 30 degrees C. The CD of RecA increases slightly with pH (up to 7.8) but is constant between pH 6.0 and 6.8. At pH below 6.0 or higher temperature (40 degrees C) slow irreversible denaturation of RecA occurs. The CD signal is effectively independent of salt, even in 2.2 M NaCl or 1 M sodium acetate, which is relevant regarding reported ATPase and coprotease activities promoted by salt. For high concentrations of magnesium (10 mM) at 30 degrees C the CD of RecA changes markedly and the appearance of light scattering indicates aggregation. PMID- 7882997 TI - A genetic variant of albumin (albumin Asola; Tyr140-->Cys) with no free -SH group but with an additional disulfide bridge. AB - A slow migrating variant of human serum albumin, present in lower amount than the normal protein, has been detected by routine clinical electrophoresis at pH 8.6 in two members of a family living in Asola (Lombardia, Italy). Ion-exchange chromatography of serum samples failed to separate the normal protein from the variant. Analysis of the albumin peak by SDS/PAGE revealed that the variant had a lower apparent molecular mass than its normal counterpart. However, the abnormal band was not detectable when the separation was performed under reducing conditions or when both albumins were carboxymethylated. Isoelectric-focusing analysis of CNBr fragments localized the mutation to fragment CNBr 3 (residues 124-298). This fragment was isolated on a preparative scale and subjected to tryptic digestion. Sequence determination of the abnormal tryptic peptide revealed that the variant arises from a Tyr140--> Cys substitution. This result was confirmed by DNA sequence analysis, which showed a single transition of TAT- >TGT at nucleotide position 5074. Despite the presence of an additional cysteine residue, several lines of evidence indicated that albumin Asola has no free -SH group; therefore, we propose the formation of a new S-S bond between Cys140 and Cys34, the only free sulphydryl group present in the normal protein. The relatively low level of the variant in serum and its abnormal mobility on cellulose acetate electrophoresis and SDS/PAGE are probably caused by a gross conformational change of the molecule induced by the new S-S bridge. PMID- 7882998 TI - Stimulation of mitogen-activated protein kinase by thyrotropin in astrocytes. AB - We have recently reported the expression of the thyrotropin (TSH) receptor and the stimulation by TSH of type-II iodothyronine 5'-deiodinase in astrocytes. In these cells, TSH stimulated arachidonate release, but neither cAMP production, nor phosphatidylinositolbisphosphate hydrolysis, as described in the human thyroid gland. Here we report, in contrast to a recent observation made in dog thyroid cells, that TSH stimulates mitogen-activated protein kinase (MAP kinase) in astrocytes. Indeed, TSH increases the tyrosine phosphorylation of the two isoforms of MAP kinase expressed in these cells, in correlation with both a slower electrophoretic migration of the tyrosine phosphorylated species and an enhanced enzymic activity measured on a specific substrate peptide. This stimulation of MAP kinase by TSH was specifically inhibited by incubation of astrocytes in the presence of human blocking anti-(TSH receptor) IgG, and by immunoprecipitation of TSH with monoclonal anti-TSH IgG. In astrocytes, TSH was neither mitogenic by itself, nor modified significantly the basic-fibroblast growth-factor-induced mitogenesis. The stimulation of MAP kinase by TSH was not affected by treatment with pertussis toxin, suggesting guanine-nucleotide-binding regulatory protein i/o was not implicated in this TSH effect. Our model will allow the study of the stimulation of MAP kinase by TSH without interference either from cAMP or from phosphoinositide signalling pathways. PMID- 7882999 TI - Recombinant analysis of human alpha 1 (XVI) collagen. Evidence for processing of the N-terminal globular domain. AB - The N-terminal non-collagenous domain NC11 of the human collagen alpha 1 (XVI) chain was obtained as a recombinant 35-kDa protein from stably transfected kidney cell clones. This form had undergone proteolytic trimming at a basic cleavage motif indicating a similar release in vivo. Domain NC11 showed a globular shape after rotary shadowing and was resistant to neutral proteases. Specific antibodies could be raised against recombinant NC11 and were used for the analysis of other cell clones transfected with the full-length alpha 1 (XVI) chain. Immunoprecipitation of detergent extracts of metabolically labelled cells demonstrated the presence of disulfide-bonded 200-kDa polypeptides possessing NC11 epitopes. This material was partially resistant to pepsin, indicating the formation of alpha 1 (XVI) chain homotrimers with a triple-helical conformation. Yet a substantial proportion of these homotrimers was degraded to fragments of variable size (35-150 kDa) when secreted into the culture medium. Several of these fragments could be obtained on a semi-preparative scale from cells grown in hollow fiber cassettes and showed substantial hydroxylation of proline, consistent with triple-helix formation. Edman degradation demonstrated the origin of some from the N-terminal and of one from a more C-terminal position of collagen XVI. This extensive degradation may be explained by the release of NC11 and by further cleavages within some of the nine interruptions of the triple helical domain of the alpha 1(XVI) chain. Whether this process also occurs in situ remains to be shown. PMID- 7883000 TI - Functioning and regioselectivity of the lipase of Candida parapsilosis (Ashford) Langeron and Talice in aqueous medium. New interpretation of regioselectivity taking acyl migration into account. AB - The lipase of Candida parapsilosis catalyses the formation of esters in aqueous media. In addition, the hydrolytic activity of the enzyme has been described in a recent publication as being selective for the 2 position, which is extremely rare. These features led to deeper investigation of the functioning and regioselectivity of the lipase in a biphasic aqueous medium. It is shown that, in addition to hydrolysis, the lipase of C. parapsilosis catalyses an alcoholysis reaction in the strict sense of the term, i.e. the transfer of fatty acyls groups from acylglycerols to various alcohols without direct involvement of water. In the presence of alcohol in the aqueous medium, alcolysis occurred preferentially to hydrolysis. The enzyme thus displays transferase activity in which the acyl acceptor may be either water or alcohol. This activity is not stereospecific to either the acyl donor or acceptor. Hydrolysis and alcoholysis of monooleoylglycerols, dioleoylglycerols and trioleoylglycerols were studied successively. Investigation of the regiospecificity of alcoholysis in the presence of the lipase of C. parapsilosis showed that the selectivity of hydrolysis for the 2 position was, in fact, only apparent. In certain cases, and particularly when the initial substrate was a triacylglycerol, the similtaneous functioning of the two hydrolysis and alcoholysis reactions led to the appearance of equivalent quantities of 1,2(2,3)-diacylglycerol and 1,3-diacylglycerol in the reaction mixture; this proportion might then be interpreted as the result of selectivity of the hydrolysis reaction for position 2 of the triacylglycerol. PMID- 7883001 TI - Mutation of the conserved Gly94 and Gly126 in elongation factor Tu from Escherichia coli. Elucidation of their structural and functional roles. AB - All guanine-nucleotide-binding proteins cycle between an inactive, GDP-bound and an active, GTP-bound conformation whereby they function as molecular switches. Elongation factor Tu from Escherichia coli is used as a model for defining residues important in the switch mechanism. Gly94 and Gly126 were separately mutated to alanine residues to study their role in the switch mechanism. The mutant proteins are denoted [G94A]EF-Tu and [G126A]EF-Tu, respectively. Both mutations affect the affinities for guanine nucleotides considerably, resulting in a decrease in the characteristic preference for GDP over GTP. Furthermore the [G94A]EF-Tu mutant possesses an increased GTPase activity. The aminoacyl-tRNA affinity is much reduced for [G94A]EF-Tu, as reflected in an increase of the dissociation rate constant for the ternary complex by a factor of 40. Surprisingly, however, both mutants in their GDP forms have a low, but significant affinity for aminoacyl-tRNA, which is not seen for the wild-type elongation factor Tu. The mutants only exhibit minor changes compared to the wild type with respect to in vitro translation of a poly(U) messenger. PMID- 7883002 TI - Mutation of the conserved Gly83 and Gly94 in Escherichia coli elongation factor Tu. Indication of structural pivots. AB - Elongation factor Tu from Escherichia coli cycles between an active conformation where GTP is bound, and an inactive conformation where GDP is bound. Between the two conformations, elongation factor Tu undergoes major structural changes. The aim of this work has been to reveal the role of two very well conserved glycine residues, Gly83 and Gly94, in the switch mechanism. Gly83 has been mutated alone or in combination with Gly94, both glycine residues being mutated to alanine. Enzymic characterisation of the two mutants have shown that they have an altered nucleotide affinity, a decrease in aminoacyl-tRNA affinity, an increase in intrinsic GTP hydrolysis, different behaviours in effector stimulation of the intrinsic GTPase activity, and that they are completely unable to sustain poly(Phe) synthesis in an in-vitro poly(U)-directed system. Our results indicates that particularly Gly83 is an important pivot point in elongation factor-Tu. PMID- 7883003 TI - Proteolytic processing of particle-associated retroviral polyproteins by homologous and heterologous viral proteinases. AB - Retroviral proteinase(PR)-catalyzed cleavage of the viral Gag and Gag-Pol polyproteins within the nascent virus particle is required for productive viral infection. Kinetic characterization and specificity analyses have been reported for several retroviral PR using oligopeptide substrates. In this study, we performed a comparative analysis of PR from avian, bovine, simian and human retroviruses using polyproteins of human immunodeficiency virus (HIV) type 1 or avian leukosis virus as substrates. Polyproteins were derived from immature virus like particles purified from culture medium of transfected or recombinant baculovirus-infected cells. Specific cleavage to the correct size intermediate and end products occurred in the presence of detergent and homologous PR. HIV-1 PR cleaved its Gag precursor to completion at a concentration of approximately 25 nM but cleaved the Gag-Pol precursor incompletely even at fourfold higher PR concentration. In contrast to the requirement for high ionic strength for peptide cleavage reported previously, we found that Gag protein cleavage by HIV-1 PR proceeded best at low ionic strength, for both of the protein substrates tested. HIV-2 PR was approximately sixfold less active than HIV-1 PR. PR from avian myeloblastosis-associated virus (MAV) yielded efficient cleavage of the HIV-1 polyprotein only at concentrations above 1 microM. Both enzymes were stimulated by high salt and their cleavage products were identical or very similar to those of HIV-1 PR. A mutant of MAV PR engineered to cleave HIV-1 peptide substrates did not cleave the HIV-1 polyprotein at a concentration of 0.4 microM. The PR of Mason Pfizer monkey virus cleaved this polyprotein very poorly, whereas PR of bovine leukemia virus cleaved it, albeit at different sites. PMID- 7883004 TI - Characterization of phospholipase A2 activity in reticulocyte endocytic vesicles. AB - Electron spin resonance spectroscopy was used to investigate the presence of phospholipase A2 activity in endocytic vesicles prepared from reticulocytes and to define some of its characteristics. Using spin-labeled phospholipid analogues, we measured the hydrolysis rate of the ester bond at position 2 during incubation with reticulocyte endocytic vesicles. We have shown that this phospholipase A2 activity was membrane-associated, enriched in endocytic vesicles as compared to cytosol and plasma membrane. Enzymic activity was also observed in exosomes, vesicles coming from the endocytic compartment and released by reticulocytes during their maturation in erythrocytes. Neither the hydrolytic activity nor the membrane association was found to be Ca(2+)-dependent. Spin-labeled phospholipids with choline and serine polar heads were better substrates than glycerophosphoethanolamine analogues. Optimal pH was found to be close to neutral. 5,5'-Dithiobis(2-nitrobenzoic acid) and diisopropyl fluorophosphate very efficiently inhibited spin-labeled phospholipid hydrolysis. This phospholipase A2 activity was confirmed using a radioactive assay, although with much lower sensitivity. (E)-6-(Bromomethylene)-tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one, a specific mechanism-based inhibitor of calcium-independent phospholipases A2, was found to abolish the enzymic activity present in endocytic vesicles. PMID- 7883005 TI - Resistance in a laboratory population of Culex quinquefasciatus (Diptera: Culicidae) to Bacillus sphaericus binary toxin is due to a change in the receptor on midgut brush-border membranes. AB - Direct binding experiments with isolated brush border membrane fractions (BBMF) from larvae of a susceptible laboratory strain of Culex quinquefasciatus Say, indicated the presence of a single class of Bacillus sphaericus binary toxin receptors. The dissociation constant (Kd) was approximately 11 nM and the maximum binding capacity (Bmax) approximately 8 pmol/mg BBMF protein. Similar binding experiments with a field population of C. quinquefasciatus that had been selected in the laboratory to more than 100,000-fold resistance to B. sphaericus binary toxin failed to reveal the presence of any specific binding. Thus this resistant strain had lost the functional receptor for B. sphaericus toxin. The binding characteristics of BBMF from the F1 larval progeny (susceptible females x resistant males) were very close to those of the parental susceptible strain, consistent with the resistance being recessive. PMID- 7883006 TI - Splice variants of the human EP3 receptor for prostaglandin E2. AB - The EP3 receptor for prostaglandin E2 (PGE2) mediates various biological activities such as uterine contraction, inhibition of gastric acid secretion, presynaptic inhibition of neurotransmitter release and potentiation of platelet aggregation. In an attempt to understand the molecular basis of this diversity of biological function, we cloned full-length cDNAs encoding EP3 receptors for PGE2 from human uterus cDNA libraries. Seven cDNA variants were identified which code for six distinct EP3-receptor isoforms. Sequencing revealed that the receptor isoforms differ in their intracellular C-terminal domains. Southern blot experiments indicate that the isoforms are generated by alternative splicing. The EP3-receptor gene is expressed in various tissues with high expression in kidney and pancreas, as demonstrated by Northern blot analysis. All receptors, stably expressed in baby hamster kidney (BHK) cells, bind PGE2 specifically with similar Kd of 2.2-5.8 nM. The binding of [3H]PGE2 is competed with by unlabelled prostaglandins in the order sulprostone (a PGE2-like agonist) approximately PGE2 >> PGF2 alpha > Iloprost (a prostacyclin analogue) > PGD2, which is specific for EP3 receptors. Analysis of the signal-transduction pathways demonstrated that all receptors respond with inhibition of forskolin-induced cAMP accumulation with an IC50 of 0.1-3 nM PGE2. In addition, some isoforms induce an increase in intracellular free calcium ([Ca2+]i) at PGE2 concentrations greater than or equal to 10 nM. These results may offer an explanation for the different physiological responses observed in various tissues following activation of EP3 receptors. PMID- 7883007 TI - Inhibition of protein synthesis by the heme-controlled eIF-2 alpha kinase leads to the appearance of mRNA-containing 48S complexes that contain eIF-4E but lack methionyl-tRNA(f). AB - Phosphorylation of the initiation factor eIF-2 by the heme-regulated eIF-2 alpha kinase (HCR) results in pronounced inhibition of protein synthesis and of binding of Met-tRNA(f) to 40S subunits in reticulocyte lysates. This inhibition is associated with the appearance of a more rapidly sedimenting 48S complex; this contains mRNA detectable by poly(U) hybridization, but not Met-tRNA(f). In contrast, 48S complexes that accumulate in the presence of the initiation inhibitor edeine contain both Met-tRNA(f) and mRNA. We have compared the composition of the particles that accumulate in the presence of HCR with those seen in the presence of edeine and find that both particles contain the cap binding protein, eIF-4E. Moreover, both particles exhibit a buoyant density of 1.40 g/ml in CsCl equilibrium density gradients. This is consistent with the presence of 500-700 kDa of protein additional to ribosomal structural protein, and suggests the presence of eIF-3 on both types of 48S complex. Lysates pre treated with HCR and then treated with edeine show the ability to accumulate 48S complexes containing Met-tRNA(f), though at a slower rate than control lysates. These observations are discussed in the light of mechanisms previously suggested for the appearance of 48S particles following HCR treatment. In addition, we have observed association of eIF-4E with polysomes and 80S monosomes in reticulocyte lysates, suggesting that this factor may not be released immediately following the binding of the 40S ribosomal subunit to the 5' end of the mRNA. PMID- 7883008 TI - The binding of divalent cations to Escherichia coli alpha-haemolysin. AB - alpha-haemolysin, an extracellular protein toxin of Escherichia coli, is known to disrupt eukaryotic cell membranes. In spite of genetic evidence of Ca(2+)-binding motifs in its sequence, conflicting results are found in the literature on the requirement of divalent cations for the membranolytic activity of the toxin. Moreover, Ca(2+)-binding sites have not been characterized to date in the native protein. The results in this paper show that when Ca2+ levels are kept sufficiently low during bacterial growth and toxin purification, membrane lysis does not occur in the absence of added divalent cations. Ca2+ and, at higher concentrations, Sr2+ and Ba2+, support the lytic activity, but Mg2+, Mn2+, Zn2+ and Cd2+ appear to be inactive in this respect. Binding of metal ions can be followed by changes in the intrinsic fluorescence of alpha-haemolysin; ions supporting lytic activity produce changes in the intrinsic fluorescence that are not caused by the inactive ones. Scatchard analysis of 45Ca2+ binding reveals three equivalent, independent sites, with Kd approximately 0.11 mM. No 45Ca2+ binding is observed when the protein is incubated with Zn2+; conversely, incubation with Ca2+ prevents subsequent binding of 65Zn2+. In the light of three dimensional data available for a structurally related protein, alkaline protease of Pseudomonas aeruginosa [Baumann, U., Wu, S., Flaherty, K. M. & McKay, D. B. (1993) EMBO J. 12, 3357-3364] it is suggested that alpha-haemolysin may bind a larger number of Ca2+ than the three that are more easily exchangeable and are thus detected in the 45Ca(2+)-binding experiments. In addition, structural similarities and conservation of ion-binding motifs support the hypothesis that His 859 is involved in the mutually exclusive binding of Zn2+ and Ca2+. PMID- 7883009 TI - Neb-colloostatin, a second folliculostatin of the grey fleshfly, Neobellieria bullata. AB - During the purification of trypsin-modulating oostatic factor (TMOF) of the grey fleshfly Neobellieria bullata, a new factor with oostatic activity was discovered. We report herein its purification, primary structure and effects on oocyte development. Its amino acid sequence was determined as H SIVPLGLPVPIGPIVVGPR-OH. Due to structural sequence similarities with parts of several known collagens and its oostatic activity, we named it Neb-colloostatin. The synthetic peptide inhibits yolk uptake by previtellogenic oocytes and might have a role in the absence of yolk deposition in penultimate oocytes. Neb colloostatin does not inhibit trypsin biosynthesis in the gut or ecdysone biosynthesis by larval ring glands. It decreases vitellogenin concentrations in the hemolymph by an unknown mode of action. The role of extracellular matrix proteins in the feedback control of growth is discussed. PMID- 7883010 TI - Amino acid substitutions in the yeast Pichia stipitis xylitol dehydrogenase coenzyme-binding domain affect the coenzyme specificity. AB - Directed mutagenesis has been used to identify a set of amino acids in the Pichia stipitis xylitol dehydrogenase, encoded by the xylitol dehydrogenase gene XYL2, which is involved in specific NAD binding. Within the binding domain, a characteristic beta alpha beta-fold is centered around a glycine motif GXGXXG also containing conserved aspartate and lysine/arginine residues. The mutation D207-->G and the double mutation D207-->G and D210-->G increased the apparent Km for NAD ninefold and decreased the xylitol dehydrogenase activity to 47% and 35%, respectively, as compared to the unaltered enzyme. The introduction of the potential NADP-recognition sequence (GSRPVC) of the alcohol dehydrogenase from Thermoanaerobium brockii into the xylitol dehydrogenase allowed the mutant enzyme to use both NAD and NADP as cofactor with equal apparent Km values. Although this mutant enzyme displayed an unaltered NADP acceptance, the reduction of the NAD specificity in the stably expressed enzyme variant is an important first step towards the long-term goal to reverse the coenzyme specificity from NAD to NADP. The mutagenized XYL2 gene could still mediate growth of Saccharomyces cerevisiae transformants on xylose minimal-medium plates when expressed together with the xylose reductase gene (XYL1). PMID- 7883011 TI - Variations in fluorescence and enzymic properties of bovine dihydrofolate reductase.NADPH complex during the slow conformational change induced by coenzyme binding. AB - When NADPH was added in large excess to bovine dihydrofolate reductase (H2folate reductase), there was a slow isomerization process between two conformers of the binary complex (B1<-->B2), as shown by changes in the fluorescence properties. Thus, we monitored the time dependence of (a) the quenching of protein intrinsic fluorescence intensity, (b) the polarization state of the fluorescence light emitted by NADPH.H2folate reductase complexes and (c), from a more biological point of view, the enzymic activity of binary complex solutions. The kinetics for these three processes were in good agreement using the same temperature conditions. Furthermore, fluorescence studies provided information on the NADPH environment in the binary complex. As soon as NADPH bound to H2folate reductase, light emitted by the invariant Trp24 residue located within the coenzyme-binding site was quenched by an energy-transfer process. Moreover, Trp57 and/or Trp113 emissions were partially quenched. The subsequent NADPH-bound protein conformational change caused an additional quenching, probably of Trp57 and/or Trp113 emissions. Thus, NADPH.H2folate reductase conformation was modified but no change was observed at the coenzyme-binding site, at least in our fluorescence study. These results were confirmed by polarization measurements. The conformational change, as well as the instantaneous NADPH binding, resulted in a more rigid form of the protein, as shown by an increase in steady-state anisotropy values. Finally, the isomerization process led to a more active enzymic form. PMID- 7883012 TI - The interaction of synthetic templates with eukaryotic DNA primase. AB - The template interaction of calf thymus and human placenta DNA primases has been investigated. Using oligothymidylates, we showed that a template consisting of ten monomeric units was the critical size for interaction with the enzyme. The hydrophobic effect is likely to be a major factor determining template recognition by the DNA primase. The correlation between the template affinity with the enzyme and the octanol-water hydrophobic scale confirms this suggestion. In addition, the electrostatic interaction between the phosphate group of the template and side chains on the enzyme probably increases template affinity. Using methylated poly(dA), we found that the first nucleotide base of the primer should be more hydrophobic than the corresponding nucleotide base of the template. A model for the mechanism of action of DNA primase is suggested on the basis of data presented in this study and previous findings. According to this model, (a) DNA primase binds ten nucleotides of the template; (b) the synthesis of primer up to the formation of a decamer occurs processively and competes with template binding of the enzyme; (c) the conditions under which the nucleotides are incorporated into the RNA product change during the extension of the primer, and these changes are responsible for switching from primase to polymerase activity. The template specificity of DNA primase is likely to play an important role in the initiation and regulation of DNA replication. PMID- 7883013 TI - Enoyl-CoA hydratase and isomerase form a superfamily with a common active-site glutamate residue. AB - Mitochondrial 2-enoyl-CoA hydratase (mECH) and 3,2-trans-enoyl-CoA isomerase (mECI), two enzymes which catalyze totally different reactions in fatty acid beta oxidation, belong to the low-similarity hydratase/isomerase enzyme superfamily. Their substrates and reaction mechanisms are similar [Muller-Newen, G. & Stoffel, W. (1993) Biochemistry 32, 11,405-11,412]. Glu164 of mECH is the only amino acid with a protic side chain that is conserved in these monofunctional and polyfunctional enzymes with 2-enoyl-CoA hydratase and 3,2-trans-enoyl-CoA isomerase activities. We tested our hypothesis that Glu164 of mECH is the putative active-site amino acid responsible for the base-catalyzed alpha deprotonation in the hydratase/dehydrase and isomerase reaction. We functionally expressed rat liver mECH wild-type and [E164Q] mutant enzymes in Escherichia coli. Characterization of the purified wild-type and mutant enzymes revealed that the replacement of Glu164 by Gln lowers the kcat value more than 100,000-fold, whereas the Km value is only moderately affected. We have demonstrated in a previous study that Glu165 is indispensable for the 3,2-trans-enoyl-CoA isomerase activity. Taking these results together, we conclude that the conserved glutamic acid is the essential basic group in the active sites of 2-enoyl-CoA hydratase (Glu164) and 3,2-trans-enoyl-CoA isomerase (Glu165), and that these enzymes are not only evolutionarily but also functionally and mechanistically related. PMID- 7883014 TI - cDNAs for S-adenosyl-L-methionine decarboxylase from Catharanthus roseus, heterologous expression, identification of the proenzyme-processing site, evidence for the presence of both subunits in the active enzyme, and a conserved region in the 5' mRNA leader. AB - S-Adenosyl-L-methionine decarboxylases (AdoMetDC) are pyruvoyl-dependent enzymes producing the aminopropyl group for spermidine biosynthesis, and this reaction is the rate-limiting step in polyamine biosynthesis. We characterized cDNAs from Catharanthus roseus (Madagascar periwinkle) and investigated the enzyme after heterologous expression. The largest cDNA (1842 bp) had an 5' leader of 469 bp and encoded a protein of 357 residues and 30-35% identity with mammalian AdoMetDC. The proenzyme expressed in Escherichia coli was processed into active enzyme, and the processing site was identified by site-directed mutagenesis as the second Ser in the sequence Leu-Ser-Glu-Ser-Ser. The analysis of affinity purified proteins indicated that the active enzyme contained both subunits. The Km for S-adenosyl-L-methionine was 35-40 microM, and the enzyme activity was not stimulated by putrescine. The 5' leader of the mRNA contained start and stop codons for a polypeptide of 51 amino acids, and this region was conserved in the 5' leaders of other plant AdoMetDC mRNAs. The putative polypeptide had no similarity with the hexapeptide responsible for modulation of AdoMetDC mRNA translation in mammals. The possibility is discussed that plants evolved a different type of translational regulation. PMID- 7883015 TI - The effect of the protein matrix proximity on glycan reactivity in a glycoprotein model. AB - A series of biotinylated glycan-Asn derivatives has been synthesized containing either no extension arm between biotin and Asn (glycan-biotinyl Asn) or containing HN(CH2)nCO extension arms of differing lengths, where n denotes the number of methylene groups in the arm (glycan-biotinyl[HN(CH2)nCO]Asn, n = 1-5). The glycan structures used were Man6GlcNAc2-, Man5GlcNAc2-, GlcNAcMan5GlcNAc2- and Gal2GlcNAc2Man3GlcNAc2-, the substrates for mannosidase I, GlcNAc transferase I, mannosidase II and sialyltransferase, respectively. Each family of substrates was subjected to the action of its respective enzyme in the absence and in the presence of streptavidin, and the relative rate of processing (in the presence of UDP-GlcNAc and the mannosidase II inhibitor, swainsonine for GlcNAc transferase I and CMP-sialic acid for sialyl transferase) was measured to evaluate the effect of the proximity of the protein matrix on the glycan substrate quality. Mannosidase I was found to be strongly inhibited by the protein matrix in the proximal as well as in the distal positions relative to the glycan substrate. In contrast, GlcNAc transferase I and mannosidase II, which were both strongly inhibited by the proximal substrate complexes (no extension arm) showed complete release of the inhibition even with the shortest (n = 1) extension arm. Sialyl transferase showed inhibition of both reaction steps in the proximal complex, and complete release of the inhibition of the first step, but not the second step, in the distal complexes. The results show that the availability of different glycan substrates in a given protein environment reflects, to a great extent, the nature of each individual enzyme. The mechanisms by which the protein matrix affects glycan processing are proposed to involve simple steric effects, as well as more subtle effects of the protein in permitting or preventing certain active glycan conformations to form. PMID- 7883016 TI - Molecular characterisation of the ADP/ATP-transporter cDNA from the human malaria parasite Plasmodium falciparum. AB - We have isolated a cDNA sequence encoding the ADP/ATP transporter in Plasmodium falciparum. The sequence analysis revealed an open reading frame encoding 301 amino acids and showed significant similarities to known eukaryotic translocases such as that of Chlorella (up to 67.2% identity) and the human transporter (61.2%). RNA blot analysis showed the presence of mRNA encoding for a 33.7-kDa ADP/ATP transporter. During the cell cycle of the parasite the expression levels of the transcripts fluctuate. The mitochondrial ADP/ATP transporter could play a role in energy metabolism of P. falciparum and makes this transporter an excellent target for chemotherapy. PMID- 7883017 TI - Kinetic analysis of the non-phosphorylated, in vitro phosphorylated, and phosphorylation-site-mutant (Asp8) forms of intact recombinant C4 phosphoenolpyruvate carboxylase from sorghum. AB - Steady-state kinetic analyses were performed on the non-phosphorylated, in vitro phosphorylated and phosphorylation-site mutant (Ser8-->Asp) forms of purified recombinant sorghum C4 phosphoenolpyruvate (P-pyruvate) carboxylase (EC 4.1.1.31) containing an intact N-terminus. Significant differences in certain kinetic parameters were observed between these three enzyme forms when activity was assayed at a suboptimal but near-physiological pH (7.3), but not at optimal pH (8.0). Most notably, at pH 7.3 the apparent Ki for the negative allosteric effector L-malate was 0.17 mM, 1.2 mM and 0.45 mM while the apparent Ka for the positive allosteric effector glucose 6-phosphate (Glc6P) at 1 mM P-pyruvate was 1.3 mM, 0.28 mM and 0.45 mM for the dephosphorylated, phosphorylated and mutant forms of the enzyme, respectively. These and related kinetic analyses at pH 7.3 show that phosphorylation of C4 P-pyruvate carboxylase near its N-terminus has a relatively minor effect on V and Km (total P-pyruvate) but has a dramatic effect on the extent of activation by Glc6P, type of inhibition by L-malate and, most especially, Ka (Glc6P) and Ki (L-malate). Thus, regulatory phosphorylation profoundly influences the interactive allosteric properties of this cytosolic C4 photosynthesis enzyme. PMID- 7883018 TI - Two distinct regions of Ras participate in functional interaction with GDP-GTP exchangers. AB - We have previously implemented a combined genetic/biochemical approach, for analysis of insertion-deletion mutants, to identify sites of Harvey-Ras participating in the interaction with guanine nucleotide exchangers, using the yeast Cdc25 as a model exchanger. We showed that positions 101-106 may be required for catalyzed exchange. We here present a further improved strategy to define more precisely the residues on Ras participating in this interaction. Non conservative replacements at positions 103 or 105 abolished response to Cdc25 while substitutions at positions 102 or 104 were partially affected. The same substitutions had no effect on coupling to adenylyl cyclase. Since the strategy enables us to assess Ras functional interaction with both the exchanger and effector simultaneously, we have also examined the effect of substitutions in the distal part of the switch II region (amino acids 69-78). In contrast to other reports, substitutions at positions 69 or 73 prevented Cdc25 response while mutations at position 74 did not prevent this interaction. However, all these substitutions partly affected cyclase activation. These findings establish the crucial role of the 102-105 region in the catalyzed exchange reaction and suggest that the 69-74 area would be required for the functional interaction with both exchangers and effector molecules. PMID- 7883019 TI - Isolation of a human cerebral imidazoline-specific binding protein. AB - The first isolation of a human brain specific imidazoline binding protein is described. This protein was obtained using affinity chromatography and was revealed with the aid of an anti-idiotypic antibody specific for imidazoline binding sites. The protein (43 kDa) differs from other imidazoline binding proteins previously isolated from peripheral tissues, in particular by being also sensitive to clonidine. PMID- 7883020 TI - Protein kinase C activation and anti-amnesic effect of acetyl-L-carnitine: in vitro and in vivo studies. AB - Drugs belonging to different chemical classes having the ability to improve behavioral performance in animal learning and memory tests may share the common ability to stimulate protein kinase C activity in rat brain cortex. In vitro acetyl-L-carnitine (100 nM) promoted in rat brain cortex slices a significant increase in particulate activity associated with lower soluble protein kinase C activity and produced a direct stimulation of the enzyme in both the cortex and hippocampus. In vivo a significant increase in particulate protein kinase C activity was observed in the group of rats treated with 60 mg/kg acetyl-L carnitine, a dose shown to be effective in improving the cognitive deficits induced by scopolamine in the Morris maze test. The results suggest that acetyl-L carnitine increases particulate protein kinase C activity in the cortex both in vitro and in vivo. This effect in the in vivo experiments seems to be observed only with doses that are effective in improving the performance of rats in a spatial learning task. PMID- 7883021 TI - Reduction of in vivo striatal 5-hydroxytryptamine release by 8-OH-DPAT after inactivation of Gi/G(o) proteins in dorsal raphe nucleus. AB - 5-HT1A receptor agonists reduce firing-dependent terminal 5-HT synthesis and release by activating somatodendritic 5-HT1A receptors. We have examined the effects of 8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT, 0.1 mg/kg s.c.) on in vivo striatal 5-HT release in conscious rats with somatodendritic 5-HT1A receptors inactivated by the application of pertussis toxin in the dorsal raphe nucleus. The uncoupling of 5-HT1A receptors from hyperpolarizing potassium channels was demonstrated by the inability of the intra-raphe application of citalopram to reduce striatal release (control animals had a 47% reduction, an effect prevented by previous treatment with the 5-HT1A antagonist (-) tertatolol). Yet 8-OH-DPAT (0.1 mg/kg s.c.) decreased striatal 5-HT release by 66% (peak effect) in pertussis toxin-treated rats, a value comparable to that found in naive animals (74%). This raises the possibility that other 8-OH-DPAT sensitive serotonergic receptors different from 5-HT1A autoreceptors may be involved in the control of terminal 5-HT release. PMID- 7883022 TI - 8-OH-DPAT attenuates the dexfenfluramine-induced increase in extracellular serotonin: an in vivo dialysis study. AB - Rats with frontocortical microdialysis probes were treated with dexfenfluramine or dexfenfluramine with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) pretreatment. Dexfenfluramine (10 mg/kg i.p.) increased extracellular serotonin (5-hydroxytryptamine, 5-HT) (calculated area under the curve (AUC) for the 0 to 105-min period after dexfenfluramine treatment = 8.22 +/- 2.66 pmol 5-HT). Systemic (0.025 mg/kg i.p.) or local (0.01 microM into the dorsal raphe nucleus) 8-OH-DPAT pretreatement decreased the dexfenfluramine response (AUC: 1.03 +/- 0.07 and 0.44 +/- 0.04 pmol 5-HT, respectively). This result might be explained by the decrease in 5-HT neuronal discharge caused by somatodendritic 5-HT1A autoreceptor activation, and suggests that the 5-HT releasing effect of dexfenfluramine in vivo depends on nerve terminal depolarization. PMID- 7883023 TI - Oxidized lipoprotein(a) inhibits endothelium-dependent dilation: prevention by high density lipoprotein. AB - We assessed the effects of human native and oxidized lipoprotein(a) (150 min, 30 and 100 micrograms/ml) on endothelium-dependent vasodilation of isolated rabbit renal arteries. Vasodilation was not attenuated after incubation of arteries with native lipoprotein(a). However, when the arteries were exposed to oxidized lipoprotein(a), acetylcholine-induced vasodilation was dose dependently significantly impaired. Concomitant incubation of segments with high density lipoprotein (HDL, 0.5 mg/ml) prevented the attenuation of dilations induced by oxidized lipoprotein(a). Thus, we report for the first time that oxidized lipoprotein(a) impairs endothelium-dependent vasodilation, and that HDL prevents its inhibitory effect. PMID- 7883024 TI - Gastrin releasing peptide-preferring bombesin binding sites in human lung. AB - Characterization of bombesin binding sites in healthy human lung was performed through direct binding techniques. There was limited binding in the absence of trypsin and chymotrypsin inhibitors, suggesting important activities of both enzymes in human lung and/or increased sensitivity of the bombesin sites toward them. In human lung membranes, bombesin, gastrin releasing peptide (GRP) and GRP preferring bombesin receptor antagonists displaced [125I-Tyr4]bombesin binding with high affinities (36-177 nM), whereas neuromedin B possessed a lower affinity of 2878 nM. [D-F5Phe6,D-Ala11]bombesin-(6-13)-methyl ester, the most active GRP preferring bombesin antagonist as yet reported, had the highest affinity among all antagonists tested whereas neuromedin B had the lowest affinity. These data demonstrate that the bombesin binding sites in the human lung are of the GRP preferring type. PMID- 7883025 TI - Tolerance to peripheral, but not central, effects of ropinirole, a selective dopamine D2-like receptor agonist. AB - Studies were conducted to determine possible development, and underlying mechanisms, of tolerance to the hypotensive effects of ropinirole (4-[2 (dipropylamino)ethyl]-1-3-dihydro-2H-indol-2-one HCl), a selective dopamine receptor agonist, following twice daily oral administration to cynomolgus monkeys and spontaneously hypertensive rats (SHR). Tolerance to the hypotensive effects of the compound developed in both species within one week of repeated dosing. Tolerance which developed in rats was dose-related and could not be attributed to altered plasma/drug concentrations or be overcome by increasing the i.v. challenge dose of ropinirole. Cross-tolerance was shown to the dopamine receptor agonist bromocriptine. Similar hypotensive responses to bethanidine were seen in rats treated with ropinirole or vehicle. Tolerance to hypolocomotor effects of the compound were not apparent in the same time frame. The dopamine D2 receptor antagonist, domperidone, caused hypertension in ropinirole-but not vehicle treated rats. Results reported in this paper are not consistent with a down regulation of peripheral dopamine D2-like receptors but suggest a compensatory increase in basal sympathetic tone. PMID- 7883027 TI - Facilitation of nicotinic receptor desensitization at mouse motor endplate by a receptor-operated Ca2+ channel blocker, SK&F 96365. AB - When acetylcholinesterase was inhibited by neostigmine, SK&F 96365 (1-(beta-[3-(4 methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride) at 10 microM caused no effect on the amplitude of single endplate potentials (e.p.p.s) but shortened the decay time in mouse phrenic nerve-diaphragm preparations. However, SK&F 96365 inhibited high-frequency stimulation-evoked long-lasting depolarization of the endplate region and accelerated the run-down of trains of e.p.p.s which were eliminated within 1 s. After a train of stimulation, SK&F 96365 produced a post-tetanic depression of single e.p.p.s. The post-tetanic effect gradually dissipated with full restoration in 10-15 s. During a train of stimulation, SK&F 96365 also depressed miniature endplate potentials (m.e.p.p.s), which were restored after termination of stimuli in parallel with the recovery of e.p.p. The decay times of miniature endplate currents during recovery phases changed slightly. In control preparations not treated with neostigmine, however, SK&F 96365 did not alter the amplitude and decay time of m.e.p.p.s or e.p.p.s but accelerated the decay of succinylcholine-induced endplate depolarizations. The results suggest that SK&F 96365 facilitates nicotinic receptor desensitization in addition to blocking receptor-operated Ca2+ channels. PMID- 7883026 TI - Effect of a series of 5-HT4 receptor agonists and antagonists on steroid secretion by the adrenal gland in vitro. AB - We have previously shown that serotonin (5-hydroxytryptamine, 5-HT) stimulate corticosterone and aldosterone secretion from perifused frog adrenal gland in vitro through activation of 5-HT4 receptors. In the present study, we have used this model to investigate the effect of newly discovered 5-HT4 receptor agonists and antagonists on corticosteroid secretion. Serotonin, the benzamide derivatives (R,S)-zacopride ((R,S)-4-amino-N-(1- azabicyclo[2.2.2]oct-3-yl)-5-chloro-2 methoxybenzamide, HCI) and its enantiomers, the azabicycloalkyl benzimidazole derivatives BIMU 1 (endo-N- (8-methyl-8-azabicyclo-[3.2.1]oct-3-yl)-2,3-dihydro-3 ethyl-2-oxo- 1H-benzimidazole-1-carboxamide, HCl) and BIMU 8 (endo-N-(8-methyl-8- azabicyclo-[3.2.1]oct-3-yl)-2,3-dihydro-(1-methyl)ethyl-2-oxo-1H- benzimidazole-1 carboxamide, HCl) were all capable of enhancing corticosterone and aldosterone secretion in a dose-dependent manner. Serotonin was the most potent stimulator of steroidogenesis (EC50 = 1.5 x 10(-7) M) while the potency of the benzamide and the benzimidazolone derivatives was approximately 10 times lower. The rank order of efficacy of the different 5-HT4 receptor agonists was: (S)-zacopride > BIMU 8 = (R,S)-zacopride > BIMU 1 = (R)-zacopride = 5-HT. The stimulatory effects of 5 HT and the benzimidazolone derivatives on corticosteroid secretion were not additive, suggesting that they activated the same receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883028 TI - Prolongation of the QT interval by dofetilide modulates rate-dependent effects of mexiletine on intraventricular conduction. AB - Prolongation of action potential duration during treatment with agents that possess class I antiarrhythmic activity may result in a clinically relevant increase in Na+ channel block. In order to test this hypothesis in vivo, the effect of QT prolongation on intraventricular conduction was assessed during administration of mexiletine. Epicardial His bundle recordings were made in anesthetized guinea pigs. After abolition of spontaneous sinus node activity by application of high-frequency current to the sinus node area, the hearts were paced via the left atrium. Administration of the class III antiarrhythmic agent dofetilide (10 micrograms/kg i.v.; n = 6) significantly prolonged QT intervals without a significant effect on HV intervals. Infusion of mexiletine (bolus 2 mg/kg + 0.18 mg/kg per min i.v.; n = 6) produced significant increases in HV intervals at cycle lengths of 200 and 300 ms. Subsequent addition of dofetilide (20 micrograms/kg i.v.) to mexiletine induced similar increases in QT intervals as single treatment with 10 micrograms/kg dofetilide and significantly enhanced the rate-dependent conduction slowing. Upon abruptly decreasing the pacing cycle length from 500 ms to 300 ms, conduction slowing developed with a rate constant of 1.0 +/- 0.2 beat-1 after mexiletine and with a rate constant of 1.1 +/- 0.2 beat-1 after subsequent addition of dofetilide (P = n.s.). After rapid stimulation at a cycle length of 250 ms the conduction slowing produced by mexiletine recovered with a time constant of 174 +/- 24 ms. No further change of this recovery time constant was observed after subsequent addition of dofetilide to mexiletine (160 +/- 19 ms, P = n.s.). Thus action potential duration, as reflected by the QT interval, is an important modulator of the magnitude Na+ channel block in vivo. The kinetic parameters of Na+ channel block produced by mexiletine, however, remain unchanged by prolongation of action potential duration after addition of dofetilide. PMID- 7883029 TI - Effects of two truncated forms of human calcitonin-gene related peptide: implications for receptor classification. AB - We investigated the possibility that human alpha-calcitonin-gene related peptide (CGRP)-(8-37) and human beta CGRP-(8-37) show some selectivity as antagonists of CGRP1 and CGRP2 receptor-mediated responses. Bindings assays showed that human alpha CGRP, human alpha CGRP-(8-37) and human beta CGRP-(8-37) showed high affinity (in the nanomolar concentration range) for CGRP receptors expressed in SK-N-MC cells and also in rat brain membrane preparations. Both human alpha CGRP (8-37) and human beta CGRP-(8-37) were potent antagonists of human alpha CGRP stimulated cAMP accumulation in SK-N-MC cells. However, both human alpha CGRP-(8 37) and human beta CGRP-(8-37) were weakly effective in antagonizing human alpha CGRP-stimulated responses in guinea-pig atria and rat vas deferens. In rat vas deferens, but not guinea-pig atria, the effects of human alpha CGRP and human alpha CGRP-(8-37) (but not human beta CGRP-(8-37)) were potentiated by thiorphan. Neither human alpha- nor human beta CGRP-(8-37) showed selectivity for supposedly CGRP1 and CGRP2 receptor-mediated responses. Furthermore, differences in the effects of the truncated CGRP analogues may reflect differences in enzyme distribution rather than the existence of CGRP receptor subtypes. PMID- 7883030 TI - Functional identification of alpha 1-adrenoceptor subtypes in human prostate: comparison with those in rat vas deferens and spleen. AB - The effects of some alpha 1-adrenoceptor antagonists (prazosin, nonselective for the alpha 1A- and alpha 1B-adrenoceptor subtypes; 5-methyl-urapidil, selective for the alpha 1A-adrenoceptor subtype; chloroethylclonidine, selective for the alpha 1B-adrenoceptor subtype) and nifedipine were compared on contractile responses to noradrenaline or phenylephrine in human prostatic tissues, rat vas deferens and spleen. In rat vas deferens, nifedipine (1 microM), but not chloroethylclonidine (100 microM), almost completely abolished noradrenaline induced contraction, the pA2 values for prazosin and 5-methyl-urapidil against noradrenaline being 9.29 and 8.55, respectively. In rat spleen, chloroethylclonidine reduced (by 57%) the maximum contraction induced by phenylephrine; nifedipine was ineffective. The log concentration-response curve was shifted significantly to the right; the pA2 values of prazosin and 5-methyl urapidil against phenylephrine were 9.45 and 7.21, respectively. In human prostatic tissues, both nifedipine and chloroethylclonidine produced significant inhibition of noradrenaline-induced contractions. Chloroethylclonidine produced a 44% reduction of the maximum contraction to noradrenaline and shifted the log concentration-response curve to the right. In contrast, nifedipine, while reducing the maximum response to a similar extent, produced a small rightward shift in the log concentration-response curve. The pA2 values for prazosin and 5 methyl-urapidil against noradrenaline were 9.21 and 7.74, respectively. The pA2 values for prazosin in these three tissues did not vary significantly, whereas that for 5-methyl-urapidil in human prostatic tissue was intermediate between that in rat vas deferens and that in rat spleen: these tissues contain primarily alpha 1A- and alpha 1B-adrenoceptor subtypes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883031 TI - Methoctramine induces nonspecific airway hyperresponsiveness in vivo. AB - We investigated the effects of subtype-selective muscarinic receptor antagonists upon aerosol antigen-induced bronchoconstriction in anesthetized guinea pigs. Neither pirenzepine (muscarinic M1 receptor-selective), 4-methylpiperidine methiodide (4-DAMP, muscarinic M3 receptor-selective), [N-iminomethyl-N'-[(2 hydroxy-2-phenyl-2-cyclohexyl)-ethyl] piperazine HCl (DAC-5945, muscarinic M3 receptor-selective), ipratropium or atropine inhibited bronchoconstriction, but methoctramine (muscarinic M2 receptor-selective) produced a dose-dependent increase in bronchoconstriction (up to 46%). Methoctramine also produced increases in bronchoconstriction induced by aerosols of histamine (up to 45%) and platelet activating factor (up to 118%), demonstrating nonspecific airway hyperresponsiveness. This effect of methoctramine was not inhibited by atropine, DAC-5945 or vagotomy and could not be attributed to altered arachidonic acid metabolism or beta-adrenergic antagonism. However, propranolol prevented methoctramine-induced airway hyperresponsiveness, suggesting that this effect resulted from the reported ganglionic blocking activity of methoctramine. In conclusion, muscarinic receptors do not appear to play an important role in antigen-induced bronchoconstriction in anesthetized guinea pigs. Furthermore, caution should be exercised in using methoctramine to characterize the roles of muscarinic receptors in airway inflammatory responses in vivo. PMID- 7883033 TI - Modulation of granuloma formation by endogenous nitric oxide. AB - We have studied the possible involvement of nitric oxide (NO) in granuloma formation induced by subcutaneous implantation in rats of carrageenin-soaked polyether sponges. Modulation of the L-arginine: NO pathway in rats was achieved by treating rats with the NO synthase inhibitor, NG-nitro-L-arginine methyl ester, as well as with L- or D-arginine. Granulomatous tissue formation, cell infiltration and NO2- production were reduced, in a dose-dependent manner, by NG nitro-L-arginine methyl ester and increased by L-arginine but not by D-arginine. These results suggest that endogenous NO plays a modulating role in granuloma formation. PMID- 7883032 TI - Role of nitric oxide in mediating non-adrenergic non-cholinergic relaxation of the cat ileocecal sphincter. AB - The participation of nitric oxide (NO) in field stimulation- or nicotine-evoked non-adrenergic non-cholinergic (NANC) relaxation of cat ileocecal sphincter was studied in vitro. During a 30 microM noradrenaline-induced contraction, both the application of electrical field stimulation (2-20 Hz, 0.2 ms, supramaximal current intensity, 10 s duration) and (-)-nicotine (10-500 microM) produced a tetrodotoxin-sensitive relaxation. The maximal relaxation was observed at 10 Hz or 100 microM (-)-nicotine. In 12 out of 19 strips the pretreatment with N omega nitro-L-arginine (100 microM) decreased the amplitude of the field stimulation evoked relaxation, while in the remaining strips the relaxation was transformed into a contraction. By increasing the concentration of N omega-nitro-L-arginine up to 1 mM all strips responded to field stimulation with a frequency-dependent tetrodotoxin-resistant contraction. N omega-Nitro-L-arginine (100 microM) completely inhibited the nicotine-induced relaxation. L-Arginine (1 mM) restored the amplitude of both field stimulation- and nicotine-evoked relaxations. These data indicate that NO appears to be involved in both field stimulation- and nicotine-evoked NANC relaxations. Evidence has been obtained for the existence of tetrodotoxin-resistant NANC contraction in cat ileocecal sphincter. PMID- 7883034 TI - Binding profile of benextramine at neuropeptide Y receptor subtypes in rat brain areas. AB - Binding studies in rat whole brain, frontoparietal cortex and brainstem membrane preparations revealed that benextramine displaced [3H]neuropeptide Y specific binding from a low and a high affinity site with IC50 values in the microM (36 +/ 2, 4.4 +/- 1.4 and 300 +/- 120 microM, respectively) and the pM (29.3 +/- 12.1, 0.35 +/- 0.11 and 0.42 +/- 0.03 pM, respectively) range, whereas in rat hippocampus benextramine displaced [3H]neuropeptide Y specific binding from one site only with an IC50 value of 22.8 +/- 5.7 microM. With the exception of frontoparietal cortex binding assay, benextramine was not able to completely inhibit [3H]neuropeptide Y specific binding revealing the presence of a benextramine nonsensitive third binding site. Benextramine pretreatment followed by membrane washing demonstrated that benextramine inhibited irreversibly both high and low affinity sites. PMID- 7883035 TI - Megestrol acetate stimulates food and water intake in the rat: effects on regional hypothalamic neuropeptide Y concentrations. AB - Megestrol acetate, a synthetic progestogen, stimulates appetite through an unknown mechanism. We tested the hypothesis that it might act, at least in part, by stimulating the activity of hypothalamic pathways containing neuropeptide Y, a potent central appetite stimulant in rats. Administration of megestrol acetate (50 mg/kg/day, n = 8) for 9 days significantly increased food and water intake compared with untreated controls (n = 8). Treated rats showed significant (90 140%) increases in neuropeptide Y concentrations in the arcuate nucleus (where neuropeptide Y is synthesized), in the lateral hypothalamic area (through which arcuate neurones project) and in the medial preoptic area, ventromedial nucleus and dorsomedial nucleus. The latter are sites of neuropeptide Y release and sensitive to neuropeptide Y-induced hyperphagia. Megestrol acetate may therefore stimulate neuropeptide Y synthesis, transport and release, and this could contribute to its appetite-stimulating effects. PMID- 7883036 TI - The sequence of a cytoplasmic intermediate filament (IF) protein from the annelid Lumbricus terrestris emphasizes a distinctive feature of protostomic IF proteins. AB - The complete cDNA clone for a cytoplasmic intermediate filament (IF) protein from the annelid Lumbricus terrestris reported here, shows an extra 42 residues in the coil 1b subdomain of the central rod, as do the IF proteins from nematodes and molluscs. These extra six heptads are also present in all nuclear lamins but not in any known vertebrate cytoplasmic IF protein. Thus, it seems that protostomic metazoa conserve a lamin-like structural element in their cytoplasmic IF proteins, which was lost in the deuterostomic metazoan branch leading to the vertebrates. PMID- 7883037 TI - Identification of the trapped calcium in the gelsolin segment 1-actin complex: implications for the role of calcium in the control of gelsolin activity. AB - The X-ray structure of the complex of actin with gelsolin segment 1 revealed the presence of two calcium ions, one bound at an intramolecular site within segment 1 and the other bridging the segment directly to actin. Although earlier calcium binding studies at pH 8.0 revealed only a single calcium trapped in the complex (and also in the binary gelsolin-actin complex), it is here shown that two calcium ions are bound under the conditions of crystallization at physiological pH. Mutation of acidic residues in either actin or segment 1 involved in ligation of the intermolecular calcium ion resulted in loss of one of the bound calcium ions at pH < 7, but not at pH 8. Thus the calcium ion trapped in the segment 1 actin complex is that located at the intramolecular site. The implications of this for gelsolin function are discussed. PMID- 7883038 TI - The observation of a hedamycin-d(CACGTG)2 covalent adduct by electrospray mass spectrometry. AB - Covalent binding of the antitumour antibiotic hedamycin to the self-complementary hexadeoxyribonucleotide 5'-CACGTG-3' has been investigated by electrospray ionization mass spectrometry (ESI-MS). Ions due to double-stranded forms of the free 5'-CACGTG-3' and the hedamycin-5'- CACGTG-3' adduct have been observed in ESI mass spectra and their identity has been confirmed by resolution of individual charge states in ESI-MS spectra. Clear evidence that specific base paired associations are being observed in ESI-MS is provided by the results of a titration experiment involving alkylated and non-alkylated complementary strands. This work demonstrates the potential of this powerful new tool for studying ligand-DNA binding. PMID- 7883039 TI - An actin-related protein from Dictyostelium discoideum is developmentally regulated and associated with mitochondria. AB - An actin-related protein (ACLA) has been identified in the cellular slime mould Dictyostelium discoideum. The complete cDNA sequence indicates that within the actin superfamily it belongs to the ARP3 family of actin-related proteins together with Arp66B from Drosophila melanogaster, Actin2 from Bos taurus, act2 from Schizosaccharomyces pombe and possibly act2 from Caenorhabditis elegans. The ACLA mRNA is regulated during development, showing a maximum between 2 and 4 h after starvation. The protein has been expressed in E. coli and antibodies raised against it. Immunofluorescence microscopy shows that ACLA protein co-localises with mitochondria; the protein copurifies with Dictyostelium mitochondria. PMID- 7883040 TI - Epidermal growth factor stimulates hydrolysis of phosphatidylinositol 4,5 bisphosphate, generation of diacylglycerol and exocytosis in mouse spermatozoa. AB - Mouse spermatozoa stimulated with epidermal growth factor (EGF) or zona pellucida (ZP) experienced phosphatidylinositol 4,5-bisphosphate hydrolysis, diacylglycerol (DAG) generation and acrosomal exocytosis. The agonists showed additive effects but the action of EGF is likely to be mediated by a distinct receptor because maximal stimulation achieved with EGF was enhanced further by ZP. Generation of DAG and exocytosis stimulated by EGF were inhibited by tyrphostin A48, indicating that tyrosine kinase activity mediates EGF action. On the other hand, pertussis toxin did not affect the EGF-induced formation of DAG or exocytosis, ruling out the involvement of sperm Gi-like proteins. These results indicate that EGF could be an important co-factor in the initiation of exocytosis in spermatozoa. PMID- 7883041 TI - Comparative thermodynamic analyses of the Fv, Fab* and Fab fragments of anti dansyl mouse monoclonal antibody. AB - In order to investigate the role of the constant domains on the antigen-binding property of the variable domains, we have carried out a comparative thermodynamic study of the anti-dansyl Fv, Fab* and Fab fragments that possess the identical amino acid sequence of the variable domains. The thermodynamic analyses have shown that binding constants, enthalpy changes and entropy changes are similar for the three antigen-binding fragments, whereas the thermal stability of Fab is much higher than that of Fv and Fab*. We have concluded that (i) the variable domains of the three antigen-binding fragments possess identical intrinsic capability for antigen binding and (ii) the two constant domains serve to improve the stability of the variable domains. PMID- 7883043 TI - Lipid specificity for membrane mediated partial unfolding of cytochrome c. AB - In this study we investigated the lipid specificity for destabilization of the native structure of horse heart cytochrome c by model membranes. From (i) the enhanced release of deuterium from deuterium-labelled cytochrome c and (ii) the increased proteolytic digestion of the protein in the presence of anionic lipids, it was concluded that these lipids are able to destabilize the native structure of cytochrome c. Changes in the absorbance at 695 nm indicated that the destabilization was accompanied by a diminished ligation of Met-80 to the heme. Beef heart cardiolipin was found to be more effective than DOPS, DOPG or DOPA, while no protein destabilization was observed in the presence of the zwitterionic lipid DOPC or, surprisingly, in the presence of E. coli cardiolipin. Experiments with mitoplasts showed that the protein can also be destabilized in its native structure by a biological membrane. PMID- 7883042 TI - The action of mercury on the binding of the extrinsic polypeptides associated with the water oxidizing complex of photosystem II. AB - Mercury (Hg2+), a sulfhydryl group reactant, was used to probe structure-function relationships in photosystem II (PSII). In the present work, we investigated the impact of mercury on the polypeptide composition of PSII submembrane preparations. Electrophoretic analysis revealed that the incubation of the membranes in the presence of mercury produces the depletion of a polypeptide of molecular weight of 33 kDa. This polypeptide corresponds to the extrinsic protein EP33 of the oxygen evolving complex removed following urea treatment. However, the two closely related extrinsic polypeptides of 16 and 23 kDa, usually removed concomitantly after urea treatment, remained unaffected after the mercury treatment. These data demonstrated the existence of an intrinsic binding site for EP23. The molecular mode of action of mercury in the oxygen evolving complex of PSII is discussed. PMID- 7883044 TI - Site-directed disulfide reduction using an affinity reagent: application on the nicotinic acetylcholine receptor. AB - The aim of this study was to present a new concept of site-directed reduction of disulfide bonds based upon the use of an affinity ligand harbouring a readily oxidizable dithiol. The cysteine bond involved in the acetylcholine binding site of the AChoR was specifically reduced by a carbamylcholine analogue. The ligand, in its oxidized form, was characterized by an affinity constant of 20 microM for the agonist binding site. In its dithiol form, it specifically reduced the disulfide between Cys-192 and Cys-193 on the alpha-subunits of the nicotinic acetylcholine receptor. This reduction needed 10 times lower concentration when carried out with site-directed reducing agent (ARA) than with DTT, and was highly specific for the alpha-subunits. The contribution of the carbamylcholine moiety of the site-directed reducing agent was clearly demonstrated in kinetic studies where reduction abilities of ARA, DTT and the methylated analogue of ARA (MeRA) were compared. At the same concentration (20 microM), DTT and MeRA had a 25 times lower initial rate of reduction than ARA. With 200 microM of DTT this initial reduction was still 4 times lower. Furthermore, the use of a maleimido undecagold cluster which specifically labeled the reduced nicotinic receptor opens the way to structural analysis of the agonist binding site by electron microscopy. These results demonstrate the potency of this kind of site-directed reducing agent for structural study of receptors or enzymes involving a disulfide bond in their active site. PMID- 7883045 TI - Alpha-latrotoxin stimulates glutamate release from cortical astrocytes in cell culture. AB - The mechanism responsible for the ability of bradykinin to cause calcium dependent release of glutamate from astrocytes in vitro was investigated. The glutamate transport inhibitor, dihydrokainate, did not block bradykinin-induced glutamate release, and bradykinin did not cause cell swelling. These data exclude the involvement of glutamate transporters or swelling mechanisms as mediating glutamate release in response to bradykinin. alpha-Latrotoxin (3 nM), a component of black widow spider venom, stimulated calcium-independent glutamate release from astrocytes. Since alpha-latrotoxin induces vesicle fusion and calcium independent neuronal neurotransmitter release, our data suggest that astrocytes may release neurotransmitter using a mechanism similar to the neuronal secretory process. PMID- 7883046 TI - Alpha-tocopherol mediated peroxidation in the copper (II) and met myoglobin induced oxidation of human low density lipoprotein: the influence of lipid hydroperoxides. AB - The principal antioxidant in human LDL, alpha-tocopherol, is converted to the alpha-tocopheroxyl radical after reaction with peroxyl radicals or Cu2+, and, if it does not terminate with peroxyl radicals, could initiate lipid peroxidation; a phenomenon called 'tocopherol mediated peroxidation'. Only in the presence of Cu2+ and low levels of lipid hydroperoxides was an alpha-tocopherol dependent decrease in the resistance of LDL to oxidation detected. This suggests that tocopherol mediated peroxidation will probably not contribute significantly as a pro-oxidant process in those individuals most at risk of developing atherosclerosis through an oxidative mechanism. PMID- 7883047 TI - Molecular cloning and expression of a cDNA for human kidney cysteine conjugate beta-lyase. AB - Kidney cysteine conjugate beta-lyase (glutamine transaminase K, kyneurenine aminotransferase, EC 2.6.1.64) metabolises the cysteine conjugates of certain halogenated alkenes and alkanes to form reactive metabolites which can produce nephrotoxicity and neurotoxicity in experimental animals and man. Using a combination of hybridisation screening and PCR techniques we have isolated a full length cDNA for human kidney cysteine conjugate beta-lyase. Comparison of the deduced amino acid sequence with that of the rat enzyme indicated an 82% overall similarity, with 90% similarity around the pyridoxal phosphate binding site, many of the changes being conservative in nature. Expression of the cDNA in Cos-1 cells resulted in the production of a cytosolic enzyme which showed both cysteine conjugate beta-lyase and glutamine transminase K activity. Preliminary mapping of the gene for human cysteine conjugate beta-lyase by PCR analysis of genomic DNA from human-rodent hybrid cells indicated that it is located on human chromosome 9. PMID- 7883048 TI - The 3'-untranslated region of brome mosaic virus RNA does not enhance translation of capped mRNAs in vitro. AB - The translation enhancing ability of cis-acting 3'-terminal untranslated region (3'-UTR) of brome mosaic virus (BMV) was examined. Two chimeric mRNA constructs translated in rabbit reticulocyte lysates contained the BMV coat protein (CP) gene and NPTI gene, respectively. It was shown that the 3'-UTR of BMV RNA enhanced the translational efficiency of uncapped but not capped messages. PMID- 7883049 TI - Phenotypic features of trehalase mutants in Saccharomyces cerevisiae. AB - In the yeast Saccharomyces cerevisiae, some studies have shown that trehalose and its hydrolysis may play an important physiological role during the life cycle of the cell. Recently, other studies demonstrated a close correlation between trehalose levels and tolerance to heat stress, suggesting that trehalose may be a protectant which contributes to thermotolerance. We had reported lack of correlation between trehalose accumulation and increase in thermotolerance under certain conditions, suggesting that trehalose may not mediate thermotolerance [Nwaka, S., et al. (1994) FEBS Lett. 344, 225-228]. Using mutants of the trehalase genes, NTH1 and YBR0106, we have demonstrated the necessity of these genes in recovery of yeast cells after heat shock, suggesting a role of these genes in thermotolerance (Nwaka, S., Kopp, M., and Holzer, H., submitted for publication). In the present paper, we have analysed the expression of the trehalase genes under heat stress conditions and present genetic evidence for the 'poor-heat-shock-recovery' phenotype associated with NTH1 and YBR0106 mutants. Furthermore, we show a growth defect of neutral and acid trehalase-deficient mutants during transition from glucose to glycerol, which is probably related to the 'poor-heat-shock-recovery' phenomenon. PMID- 7883050 TI - Processing of secretogranin II by prohormone convertases: importance of PC1 in generation of secretoneurin. AB - Secretoneurin is a recently characterized neuropeptide present in the primary amino acid sequence of secretogranin II. We investigated the proteolytic processing of secretogranin II by prohormone convertases in vivo in a cellular system using the vaccinia virus system. Both PC1 and PC2 can cleave the secretogranin II precursor at sites of pairs of basic amino acids to yield intermediate-sized fragments. Other convertases like PACE4, PC5 and furin were not active. For the formation of the free neuropeptide secretoneurin a different pattern was found. Only PC1 but none of the other convertases tested including PC2 were capable of generating secretoneurin. Our results demonstrate that the prohormone convertases PC1 and PC2 are involved in proteolytic processing of secretogranin II. The neuropeptide secretoneurin can only be generated by PC1 suggesting tissue-specific processing of secretogranin II in neurons expressing different subsets of the prohormone convertases. PMID- 7883051 TI - Ebulitins: a new family of type 1 ribosome-inactivating proteins (rRNA N glycosidases) from leaves of Sambucus ebulus L. that coexist with the type 2 ribosome-inactivating protein ebulin 1. AB - A new family of single chain (type 1) ribosome-inactivating proteins (RIPs), that we have named ebulitins, have been found in mature leaves of Sambucus ebulus L., a caprifoliaceae plant also known to contain a non-toxic two chain (type 2) RIP named ebulin I in its leaves. Ebulitins are basic proteins of M(r) 32,000, 29,000 and 29,000 for ebulitins alpha, beta and gamma, respectively. The simultaneous presence of different basic type 1 and acidic type 2 RIPs in the same plant and in the same tissue is described here for the first time and opens a new door in research into RIPs. PMID- 7883052 TI - Cyclic ADP-ribose and inositol 1,4,5-triphosphate mobilizes Ca2+ from distinct intracellular pools in permeabilized lacrimal acinar cells. AB - In permeabilized lacrimal acinar cells, cyclic ADP-ribose (cADP-ribose) and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) release Ca2+ in a dose dependent manner from distinct thapsigargin-sensitive Ca2+ pools. Ryanodine specifically blocks the Ca2+ response to cADP-ribose, whereas heparin strongly reduces the response to Ins(1,4,5)P3 application. GTP causes a rapid Ca2+ release by a ryanodine- and heparin-insensitive mechanism and potentiates Ins(1,4,5)P3 but not cADP-ribose evoked Ca2+ release. It is estimated that cADP-ribose can release 16 mumol Ca2+/l cells, whereas Ins(1,4,5)P3 can mobilize 55 mumol Ca2+/l cells. The results suggest that cADP-ribose and Ins(1,4,5)P3 release Ca2+ from distinct internal stores and that a third Ca2+ pool exists which can selectively interact with the Ins(1,4,5)P3-sensitive Ca2+ store by a GTP-mediated process. PMID- 7883053 TI - Kinetics of the unfolding-folding transition of Bacillus subtilis levansucrase precursor. AB - The reversible folding-unfolding transition of mature and precursor forms of Bacillus subtilis levansucrase were compared under physiological conditions of pH and temperature. The time constant of the folding reaction was not modified by the presence of the signal sequence and the precursor in the native form was slightly more resistant to the denaturing action of urea. However, the folding pathway could be different for each protein since a domain of the mature levansucrase underwent an independent transition which is not observed during the renaturation process of prelevansucrase. PMID- 7883054 TI - Function of N-terminal import signals in trypanosome microbodies. AB - The glycosomes of trypanosomes are related to eukaryotic peroxisomes. For many glycosomal and peroxisomal proteins, a C-terminal SKL-like tripeptide known as PTS-1 serves as the targeting signal. For peroxisomes, a second N-terminal signal (PTS-2) was demonstrated on rat 3-ketoacyl-CoA thiolase. Several glycosomal proteins do not bear a PTS-1. One such protein, fructose bisphosphate aldolase, has a PTS-2 homology at its N-terminus. To find out whether the PTS-2 pathway exists in trypanosomes, we expressed chloramphenicol acetyltransferase fusion proteins bearing N-terminal segments of either rat thiolase or trypanosome aldolase. The mammalian PTS-2 clearly mediated glycosomal import. The aldolase N terminus mediated import with variable efficiency depending on the length of the appended sequence. These results provide evidence for the existence of the PTS-2 pathway in trypanosomes. PMID- 7883055 TI - Zfyl encodes a nuclear sequence-specific DNA binding protein. AB - Zfyl is a mouse Y chromosomal gene encoding a zinc finger protein which is thought to have some function during spermatogenesis. Here we show that, when introduced into tissue culture cells, Zfyl is targeted to the nucleus. Two independent signals are present within the protein for nuclear localization. This nuclear Zfyl protein is able to bind strongly to DNA-cellulose and, using site selection assays, we have identified specific Zfyl DNA binding sites. Taken together these results suggest that Zfyl is a nuclear-located sequence-specific DNA binding protein which functions during spermatogenesis. PMID- 7883056 TI - Cytolysis of hemocytes induced by serum and plasma in three crustaceans, Panulirus japonicus, Penaeus japonicus, and Homarus americanus. AB - The effects of serum and/or plasma of three crustacean species on cellular morphology of homologous and heterologous hemocytes were observed using an in vitro short-term culture system. When hemocytes of the spiny lobster, Panulirus japonicus, isolated from hemolymph were mixed with serum of the same species, rapid cytolysis occurred in hyaline and semigranular cells. Plasma of Panulirus japonicus dialyzed against artificial sea water (dialyzed plasma) had the same cytolytic effect on hyaline and semigranular cells. Although the granular cells are not lysed, exposure to serum and plasma does produce changes in morphology and behavior (adhesion and spreading). Dialyzed plasma of the shrimp (Penaeus japonicus) and the lobster (Homarus americanus) also showed the same phenomena on homologous hemocytes. Dialyzed plasma of these three species had a less pronounced cytolytic effect on heterologous hemocytes. The cytolytic activity of the dialyzed plasma was weakened by heat treatment and inactivated by protease treatment. These results suggest that a protein factor(s) that specifically induces bursting of hyaline and semigranular cells exists in plasma of crustaceans. PMID- 7883057 TI - Inhibition of in vitro replication of the oyster parasite Perkinsus marinus by the natural iron chelators transferrin, lactoferrin, and desferrioxamine. AB - The mammalian iron-binding proteins transferrin and lactoferrin, the bactericidal peptide lactoferricin B, and the bacterial siderophore desferrioxamine were tested for their ability to inhibit the in vitro replication of the oyster parasite Perkinsus marinus. All three chelators were effective in reducing the parasite proliferation in a dose-dependent manner. Lactoferricin B, a peptide of lactoferrin that exhibits bactericidal properties unrelated to iron chelation, had no inhibitory activity on the parasite. When the chelators were partially or completely saturated with the appropriate iron equivalents, their inhibitory effects on the parasite proliferation were diminished or abolished accordingly, confirming that this activity was related to the chelator's capacity for iron sequestration. Our results indicate that the parasite has a strong requirement for soluble iron and its growth rates are correlated with iron availability. We propose that excess iron accumulation in the host Crassostrea virginica promotes parasite proliferation. P. marinus may avoid oxidative damage that would compromise its intracellular survival by exhaustion the host's intracellular selected iron pools required for superoxide and hydroxyl radical production. PMID- 7883058 TI - Surgical fusion between incompatible colonies of the compound ascidian, Botrylloides fuscus. AB - In the compound ascidian Botrylloides fuscus, allorecognition responses were observed at the colonial margin (natural growing edge) as necrotic reactions in the subcuticular region of the facing tunic. However, artificial cut surface contacts between incompatible colonies resulted in the formation of chimeras with common vascular systems, termed "surgical fusion." The occurrence of surgical fusion in B. fucus contrasts with rejection occurring under the same conditions in other botryllids. Together the two observations suggest that self-nonself recognition may be a specialized function of tunic cells and their precursors in the blood, and the fusion (vascular interconnection) is a different process than rejection with different effectors and recognition systems. In all pairwise combinations among 12 and 14 colonies, more than 60% of combinations resulted in fusion when colonies were assayed by growing edge contact. This rate of fusible combinations is much higher than those of the other botryllid ascidians previously studied. PMID- 7883059 TI - Chemotactic responses of hagfish (Vertebrata, Agnatha) leucocytes. AB - The chemotactic responses of hagfish leucocytes were tested using a variety of chemoattractants. Leucocyte migration was significantly enhanced by purified mammalian complement anaphylotoxin (C5a) and LPS-activated hagfish plasma. Checkerboard analyses confirmed that the responses of leucocytes to both of these chemoattractants were directed along concentration gradients (chemotaxis) and did not result from accelerated random movement (chemokinesis). Chemotaxis was undertaken by leucocyte fractions that were enriched in granulocytes, the predominant phagocytic cells of hagfish. The data suggest that chemotactic mechanisms may have been conserved during evolution to such a degree that mammalian chemoattractants can bind and activate chemotactic receptors on hagfish leucocytes. Moreover, hagfish appear to express plasma proteins that are structurally and functionally homologous to mammalian complement anaphylotoxins. PMID- 7883060 TI - Damselfish with neurofibromatosis exhibit cytotoxicity toward tumor targets. AB - Damselfish neurofibromatosis (DNF) is a malignant transmissible disease affecting Schwann cells, and is the only naturally occurring animal model of human neurofibromatosis type 1. The current study was designed to determine whether fish in the early stages of disease have measurable immune responses toward DNF tumor cells. Three DNF tumor cell lines were used as targets in standard 51Cr cytotoxic assays. In addition, Lutjanus griseus erythrocytes served as nonspecific targets, and concanavalon A (Con A) blasts from healthy animals served as normal target cells. Results of this study show that tumor-bearing damselfish have cells capable of destroying tumor targets but healthy animals display minimal, if any, reactivity toward the DNF tumor lines. The majority of antitumor activity resides in the spleen; the pronephros appears to contain the majority of nonspecific activity. Data also show that some of the effector cells are analogous to the nonspecific cytotoxic cells of catfish. No lysis of healthy damselfish targets was observed. Thus damselfish have cytotoxic cells capable of interacting with tumor targets, but in the majority of animals this response is not adequate to circumvent the process of tumorigenesis. PMID- 7883061 TI - Effects of transforming growth factor beta 1 on rainbow trout Oncorhynchus mykiss macrophage respiratory burst activity. AB - Natural bovine transforming growth factor beta 1 (TGF-beta 1) was found to have both enhancing and suppressing effects on the respiratory burst activity of rainbow trout, Oncorhynchus mykiss, head kidney macrophages. Incubation with TGF beta 1 alone increased respiratory burst activity using doses from 0.05 to 0.2 ng/mL. However, incubation of activated macrophages with TGF-beta 1 decreased their respiratory burst activity in a dose-dependent manner. Coincubation of macrophages with activating signals (macrophage activating factor containing supernatants and tumor necrosis factor alpha) and TGF-beta 1 inhibited the ability of such signals to increase respiratory burst activity. Similarly, pretreatment of macrophages with TGF-beta 1 prior to treatment with activating signals resulted in a time and dose-dependent decrease in activity relative to cells not treated with TGF-beta 1. These suppressive effects were largest using higher doses of TGF-beta 1 (1 ng/mL). The conservation of TGF-beta s and their possible mode of action are discussed. PMID- 7883062 TI - Variability in an MHCMosa class II beta chain-encoding gene in striped bass (Morone saxatilis). AB - The major histocompatibility complex (MHC) class II B locus of the striped bass (Morone saxatilis) was found to contain multiple forms of the class II B gene. Seven complete MHC class II B cDNA clones were isolated and sequenced, identifying five unique allelic forms of a MHC class II B gene. Among three specimens, each representing a geographically distinct population (Chesapeake Bay, MD; Roanoke River, NC; and Santee-Cooper Reservoir, SC) extensive variability was detected in the beta 1 encoding domain, which corresponds with the functional peptide-binding region (PBR) of known MHC class II molecules. The location of variable amino acid residues in the beta 1 domains corresponds with polymorphic sites observed in other teleosts and higher vertebrates. The amino acid translated beta 2 domain encoding regions, transmembrane regions, and cytoplasmic regions of the five clones correlated well with those of known vertebrate MHC class II proteins. Seventy-one percent of the variability found within the presumed PBR encoded at the MHCMosa class II B locus corresponded with that of the PBR of a human MHC class II B gene. Overall, the Mosa sequences showed greatest similarity to the MHC class II B genes of cichlid fishes, as expected from phylogenetic relationships. PMID- 7883063 TI - Apoptosis in the thymus of developing Xenopus laevis. AB - Metamorphosis in Xenopus laevis is a time when thyroxine and glucocorticoid levels rise, dramatic morphological and physiological changes take place, and tolerance is established to newly expressed adult antigens. In vitro exposure of thymocytes tested at different metamorphic stages, to the T-cell lectin, phytohemagglutinin (PHA), stimulates increased apoptosis, but incubation with the synthetic glucocorticoid, dexamethasone (DEX), fails in this regard. Altered-self antigenicity, following trinitrobenzene sulfonic acid (TNBS) treatment, increases apoptosis only in the late stages of metamorphosis. Developmentally blocked metamorphosing larvae demonstrate low thymic apoptotic rates that are also unaffected by in vitro exposure to DEX or by in vivo exposure to thyroxine, but are increased by PHA and in some individuals by TNBS. When released from blockade, their thymic apoptotic rates rise as progress through metamorphosis is renewed. Larval thymic apoptosis is glucocorticocoid- and thyroxine insensitive, but is lectin and altered-self antigen activated, particularly during postclimax stages. PMID- 7883064 TI - Effect of triiodothyronine and in vitro growth hormone on avian interleukin-2. AB - One-day-old chickens were treated with varying levels of triiodothyronine (T3) added to the diet. At 28 days of age, the IL-2-like activity in the splenocyte culture supernatants were assessed. The lowest dose of T3 (0.1 ppm) enhanced IL-2 like activity while the highest dose (1.0 ppm) was significantly suppressive. The intermediate dose elicited varying effects. Recombinant chicken growth hormone (rcGH) was added to some cultures 24 h prior to IL-2 assay. In vitro rcGH significantly depressed the IL-2-like activity of splenocytes from animals given the low T3 diet. The addition of varying concentrations of T3 in vitro to splenocytes from non-T3-supplemented chickens had no effect on the IL-2-like activity. These results indicate that in vivo supplementation of low dietary T3 but not in vitro T3 is effective in enhancing avian IL-2-like activity. The addition of rcGH in vitro can modify this response. PMID- 7883065 TI - Effects of protein tyrosine kinase inhibitors on egg activation and fertilization dependent protein tyrosine kinase activity. AB - Fertilization results in the activation of protein tyrosine kinases within minutes of sperm-egg binding, although the role of the kinase(s) involved is not clear. In the present study, we have treated sea urchin eggs with genistein, as well as other protein tyrosine kinase inhibitors, and have characterized the subsequent effect on fertilization and egg activation. Genistein treatment of sea urchin eggs inhibits the overall fertilization-dependent tyrosine kinase activity as well as the specific phosphorylation of a 350-kDa protein, but it did not inhibit cAMP-dependent kinase and had little effect on protein kinase C at concentrations less than 100 microM. Genistein, erbstatin, and tyrphostin B42 did not inhibit the early events of fertilization such as elevation of the fertilization envelope; however, later events such as pronuclear migration, DNA synthesis, and cell division were inhibited. These results suggest that protein tyrosine kinases activated following fertilization play a role in the later events of egg activation such as the initiation of pronuclear movement and entry into the S phase of the cell cycle. PMID- 7883066 TI - Two chondroitin sulfate proteoglycans differentially expressed in the developing chick visual system. AB - Two monoclonal antibodies, 2B9 and 9BA12, were used to identify and characterize two different chondroitin sulfate proteoglycans (CSPGs) associated with the embryonic chick visual system. Monoclonal antibody 2B9 recognizes a carbohydrate epitope of collagen type IX proteoglycan. Immunohistochemistry showed that collagen type IX proteoglycan was abundant in the vitreous body and meninges, but absent in brain and retina. In developing trunk regions, collagen type IX proteoglycan is segmentally distributed in the somites, appearing only in the posterior sclerotome. Monoclonal antibody 9BA12 recognizes collagen type IX proteoglycan from vitreous body and an unidentified chondroitin sulfate proteoglycan in retina and brain, herein referred to as 9BA12 CSPG. Immunohistochemistry showed that 9BA12 CSPG is present in the optic fiber layer of the retina, coinciding temporally and spatially with the onset and cessation of ganglion cell axon growth. In the trunk region, 9BA12 immunostaining appears in the developing spinal cord and throughout the sclerotome. In culture, neither the collagen type IX proteoglycan nor the brain-derived 9BA12 CSPG were able to support neurite outgrowth from retinal ganglion cell explants. In combination with basal lamina proteins, collagen type IX proteoglycan slightly inhibited neurite outgrowth and led to a stronger fasciculation of retinal axons. In contrast, 9BA12 CSPG had no inhibitory effect on the outgrowth of retinal axons and had no effect on their fasciculation. Our study demonstrates the existence of two chondroitin sulfate proteoglycans in the developing visual system of the chick. Based on the developmental expression and the results from neurite outgrowth experiments, it was concluded that the 9BA12 CSPG does not operate as a neurite outgrowth inhibitor for retinal axons. PMID- 7883067 TI - Eyespot development on butterfly wings: the focal signal. AB - The eyespot colour pattern on butterfly wings is specified in the early pupal epidermis by signals from a central "focus." In Bicyclus anynana we show that a small square of focal epidermis, grafted to a range of distal wing sites, induces eyespot formation in surrounding host tissue. Signaling is limited to the focus, and even an adjacent (parafocal) graft does not maintain its normal fate (of contributing to the eyespot) and does not influence its surroundings. Along the wing, there is an abrupt change in the epidermis, as a focus grafted to a proximal site provokes no host response. The results of several grafting experiments demonstrate that their different response properties are autonomous to small areas of the distal and proximal epidermis and that the nonresponding proximal tissue can nonetheless transmit the focal sign. The Bicyclus dorsal forewing has a small anterior and a large posterior eyespot, and we show that this results mainly from a difference in focal signals, not in the epidermal response. A grafted posterior focus induces a large eyespot, whereas an anterior focus induces a small eyespot. Furthermore, the anterior and posterior eyespots differ in proportions, and this difference also depends on the identity of the focus, not on the responding epidermis. Eyespots are specified over many cell diameters from the focus by a mechanism which could consist of one long-range signal, such as a morphogen gradient or of a cascade of short-range interactions initiated by the focus. Focal control of the difference in size and proportion between the anterior and posterior eyespot is more readily compatible with a gradient mechanism. Neither model, however, readily explains why the pattern induced by a grafted focus is smaller, but its peripheral gold annulus is broader than in the corresponding control eyespot. Also, there is no direct evidence for long-range gradients, in the butterfly wing or any other insect epithelium. PMID- 7883068 TI - Addition of purified basal lamina molecules enables Schwann cell ensheathment of sympathetic neurites in culture. AB - Our aim was to determine the effect of purified basal lamina components on the differentiation of non-myelin-forming Schwann cells accompanying rat sympathetic neurons in culture. Previous work has demonstrated that Schwann cells contacting superior cervical ganglion neurons cultured in the presence of ascorbate and serum fail to effectively deposit matrix and ensheathe neurites unless fibroblasts are also present. We questioned if an increase in the amount of available basal lamina components could mimic fibroblast-induced Schwann cell differentiation. Superior cervical ganglion neuron plus Schwann cell cultures were supplemented with purified basal lamina molecules for up to 7 weeks. The addition of laminin, type IV collagen, heparan sulfate proteoglycan, or a combination of all three components, led to increased basal lamina deposition and increased neurite ensheathment compared with cultures with no additions. In long term cultures receiving component additions, however, ensheathment was exaggerated, and the Schwann cells were hypertrophic. The ensheathing conformations adopted by these Schwann cells surpassed normal-appearing ensheathment and resembled more unusual unmyelinated nerve morphology found in vivo by others in normal senescence and in several peripheral neuropathies. These experiments show that increased availability of exogenous basal lamina components leads to increased basal lamina deposition and that basal lamina elaboration can have dramatic effects on the morphology of nonmyelinating Schwann cells. These findings suggest that influences of extracellular matrix should be considered when unusual Schwann cell/axon conformations are seen in vivo. PMID- 7883069 TI - Sperm from mice carrying one or two t haplotypes are deficient in investment and oocyte penetration. AB - The t haplotypes, mutant forms of the proximal third of mouse chromosome 17 (the t complex), contain factors that contribute to defective sperm function in fertilization. Males carrying two t haplotypes (tx/ty mice) are sterile; their sperm have very poor motility and are unable to penetrate zona-free eggs. Although males carrying one t haplotype (t/+) are fertile, genetic evidence suggests that the sperm carrying the normal form of chromosome 17 (+t) are dysfunctional in fertilization, and some or all sperm have abnormal motility. Some of the same genetic factors that cause sterility in tx/ty males probably contribute to the dysfunction of +t sperm from t/+ males; however, it is unclear which steps in gamete interaction are defective in sperm from t/+ males, or whether the defects are similar to those observed in sperm from tx/ty males. We have developed a unique low sperm:egg ratio IVF assay for sperm function in fertilization. Using this assay, we have shown that tw5/+ sperm are less able than congenic +/+ sperm to penetrate the zona (probably due to their abnormal motility) and to penetrate the zona-free oocyte. Since tw5/tw32 sperm are unable to complete these same two steps in sperm-egg interaction, these specific deficits could be involved in both transmission ratio distortion and sterility. We have also shown that tw5/tw32 sperm are deficient in their ability to bind to the zona and to the oolemma. These results suggest that t haplotypes contain loci which affect a number of sperm functions and thus could be a rich source of genes important for sperm-egg interaction. PMID- 7883070 TI - Changing distributions of extracellular matrix components during early wing morphogenesis in Drosophila. AB - A new monoclonal antibody, specific to an epitope in the carboxyl terminus of the Drosophila collagen IV molecule (basement membrane collagen) was identified. The distributions of collagen IV, laminin, and an additional extracellular molecule, the 2G2 antigen (2G2-Ag), were followed immunocytochemically during early wing development. In late third instar larvae, collagen IV and laminin surround the entire wing disc, whereas the 2G2-Ag is limited to the region of the future wing pouch. For the first few hours following eversion of the disc, all three ECM components line the basal surfaces of all epithelial cells in the wing pouch, both those destined to line the wing veins and those destined to become tightly apposed in the large intervein regions. Collagen IV and laminin persist on these cells during the two initial rounds of apposition of dorsal and ventral wing surfaces; later, they become restricted to the cells lining the veins. The 2G2-Ag disappears completely quite early in the pupal period. Collagen IV appears to be synthesized at least twice, once in the larva and a second time in the pupa; in between it is enzymatically cleaved and may be eliminated, probably by hemocytes. In an extreme allele of blistered the wing is ballooned to form a single internal space. Collagen IV and laminin line all basal wing cell surfaces early in pupal development as they do in the wild type. Later, however, they continue to line the entire cavity of the mutant wing rather than assuming a restricted distribution. In a completely veinless wing (rhomboidveinletvein), collagen IV and laminin are also present generally on basal surfaces at early times, but are completely absent between the tightly apposed wing layers later. The ECM distributions both in wild type wings and in mutants suggest that the matrix plays a role in the establishment of the wing venation pattern. One possibility, strengthened by recent findings regarding ECM receptors in Drosophila, is their involvement in dorsal-ventral wing layer adhesion. Our findings also lead us to suggest that certain sets of features which distinguish vein from intervein cells may be linked during cell differentiation and thus help to define these cell phenotypes. The features include cytoskeletal specializations and certain cell surface and ECM molecules. PMID- 7883071 TI - Up-regulation of L-type Ca2+ channel associated with the development of elevated K(+)-mediated survival of superior cervical ganglion cells in vitro. AB - We have previously shown that elevated K(+)-mediated neuronal survival correlates well with a sustained increase in cytoplasmic Ca2+ ([Ca2+]i) through the opening of L-type Ca2+ channels. Elevated K+ (40 mM), however, failed to support the survival of superior cervical ganglion (SCG) cells freshly isolated from newborn rats, while another depolarizing agent, veratridine, was able to do so, suggesting that elevated K(+)-mediated Ca2+ influx occurs in a stage-dependent manner. Indeed, sustained levels of [Ca2+]i in response to high K+ remained low (91 nM) in these neurons, but became elevated (238 nM) in SCG neurons which had been exposed to nerve growth factor (NGF) for 5-7 days and were capable of responding to elevated K+ by survival. Semiquantitative PCR measurements of L type Ca2+ channel mRNA revealed that this transcript increased dramatically during incubation with NGF for 3 days and reached a plateau level at Day 5 (seven fold per surface area or nine-fold per total volume compared to that at Day 1). These findings show that NGF-mediated up-regulation of the expression of L-type Ca2+ channel mRNA correlates with the development of elevated K(+)-mediated neuronal survival in vitro and suggest its involvement in coordinate strengthening of pre- and postganglionic synapses in rat SCG neurons. PMID- 7883072 TI - Regulation of Dictyostelium adenylylcyclases by morphogen-induced modulation of cytosolic pH or Ca2+ levels. AB - Inhibition of cAMP production and consequent inactivation of protein kinase A (PKA) by the putative morphogen ammonia has been suggested to block culmination and stalk cell differentiation in Dictyostelium. Since other weak bases mimic and weak acids act oppositely to ammonia, its effects were attributed to cytosolic or vesicular alkalinization; the latter resulting in impaired Ca2+ sequestration. We investigated whether weak bases and acids modulate the activity of the two Dictyostelium adenylylcyclases ACA and ACG in a manner consistent with their effects on development. It appeared that ammonia inhibits both ACG activity and ACA activation only transiently and does not significantly affect cAMP levels in slugs. Surprisingly, weak acids inhibit both ACA and ACG permanently, but do not affect secretion of cAMP as was suggested earlier. The effects of weak acids, which reduce cytosolic pH, are consistent with the pH dependence of ACA and ACG. In lysates, basal and GTP gamma S-stimulated ACA activity as well as ACG activity are optimal at pH 8 and are virtually absent below pH 7. ACG activity in cell lysates is completely insensitive to Ca2+, while GTP gamma S-stimulated ACA activity is maximally 50% reduced by supraphysiological Ca2+ concentrations. The observation that weak acids strongly inhibit ACA and ACG while promoting a PKA dependent process such as stalk cell differentiation suggests that in Dictyostelium PKA can be activated in the absence of cAMP production. PMID- 7883073 TI - Microtubule organization, acetylation, and nucleation in Xenopus laevis oocytes: II. A developmental transition in microtubule organization during early diplotene. AB - Confocal immunofluorescence microscopy of ovaries from juvenile frogs revealed changes in the organization, acetylation, and nucleation, of microtubules (MTs), and redistribution of gamma-tubulin (gamma-TB), during early oogenesis in Xenopus laevis. Interphase oogonia contained sparse, radially organized, MT arrays and prominent centrosomes, Acetylated MTs were not commonly found in oogonia. In contrast, small (approximately 12-25 microns), postmitotic (stage 0) oocytes contained dense, highly polarized, MT networks that exhibited little or no evidence of radical organization. Examination of stage 0 oocytes stained with antibodies to gamma-TB, in conjunction with assays of MT nucleation activity, revealed that stage 0 oocytes do contain active centrosomes. In addition, stage 0 oocytes contained numerous acetylated MTs, suggesting that arrest in meiotic prophase is accompanied by MT stabilization. Early stage I oocytes (diameters from approximately 35-50 microns) exhibited a rounded morphology and contained a dispersed, apparently disordered, MT array with a substantial population of acetylated MTs. Examination of stage I oocytes stained with gamma-TB antibodies revealed that this centrosomal protein was present in multiple cytoplasmic foci which did not function as MTOCs following cold-induced MT disassembly. The results presented indicate that the maternal centrosome is inactivated during early stage I, roughly coincident with the onset of the diplotene stage of meiotic prophase and prior to assembly of the mitochondrial mass. Our observations place constraints on the role of MTs and the maternal centrosome during specification of the animal-vegetal axis of Xenopus oocytes and raise questions regarding the mechanisms by which MT assembly and organization are regulated during oocyte differentiation. PMID- 7883074 TI - The Drosophila Wnt protein DWnt-3 is a secreted glycoprotein localized on the axon tracts of the embryonic CNS. AB - The Wnt gene family encodes highly conserved cysteine-rich proteins which appear to act as secreted developmental signals. Both the mouse Wnt-1 gene and the Drosophila wingless (wg) gene play important roles in central nervous system (CNS) development. wg is also required earlier, in the development of the embryonic metameric body pattern. We have begun to characterize the developmental expression and role of another member of the Drosophila Wnt gene family, DWnt-3. Using antisera raised to the DWnt-3 protein, we show that the protein is secreted in vivo. The early protein expression domains include the limb and appendage primordia. Late expression domains comprise the ventral cord and supraesophageal ganglia of the CNS. Notably, DWnt-3 protein accumulates on the commissural and longitudinal axon tracts of the CNS. Ectopic expression of DWnt-3 in transgenic embryos bearing a HS-DWnt-3 construct leads to specific disruption of the commissural axon tracts of the CNS. We also show that DWnt-3 does not functionally replace wg in an in vivo assay. Experiments with a tissue culture cell line transfected with a construct encoding the DWnt-3 gene show that DWnt-3 protein is efficiently synthesized, glycosylated, proteolytically processed, and transported to the extracellular matrix and medium. DWnt-3, therefore, encodes a secreted protein, which is likely to play a role in development of the Drosophila CNS. PMID- 7883075 TI - Initial axial level-dependent differences in size of avian dorsal root ganglia are imposed by the sclerotome. AB - We have recently shown that there is very early variation in dorsal root ganglia (DRG) size based on their axial position. From the time of their condensation at Stage (St.) 20 (Embryonic Day 3), before the onset of apoptosis, the ganglia in brachial segments 14 and 15 are more than 80% larger on the average than those in cervical 5 and 6. This difference in volume is due to increased numbers of cells in the brachial DRG. In addition, the rostrocaudal length was found to be significantly greater for brachial ganglia, and the greater length of the brachial ganglia was found to be correlated with a greater length of brachial than cervical sclerotomes. It was therefore proposed that the difference in DRG size at the time of gangliogenesis is likely to arise from colonization by a larger initial number of neural crest cells of the longer adjacent rostral sclerotomes in brachial somites. In the present work, we have performed two types of experiments to test this hypothesis. First, we have performed heterotopic grafts of segmental plate mesoderm from cervical to brachial levels and vice versa. In all of these grafts, the sclerotomes developed with a rostrocaudal extent (length) corresponding to their level of origin in the donor embryo. DRG that formed in the grafted mesoderm attained a length appropriate to that of ganglia developing in segments of the axial level of the donor mesoderm, not that of the host. Second, we have estimated proliferation of DRG cells at St. 20 using HNK-1/bromodeoxyuridine double-stain immunocytochemistry. The percentage of cells in S-phase at both brachial and cervical levels of the neuraxis in newly formed ganglia was observed to be the same. These two lines of evidence strongly argue that the initial difference in size between DRG at different axial levels is not intrinsic, but rather is imposed by the mesodermal microenvironment in which they develop, as is the case for DRG segmentation. This is in contrast to what may occur in the hindbrain, where determination of rhombomere identity and neural crest segmentation are thought to be intrisic to the nervous system. PMID- 7883076 TI - Arrest of stomatal initials in Tradescantia is linked to the proximity of neighboring stomata and results in the arrested initials acquiring properties of epidermal cells. AB - We examined spatial relations of arrested stomatal initials and their differentiated state on leaves of the monocotyledon Tradescantia. The placement and proximity of stomata and arrested stomatal initials to the five nearest stomata were studied to test the hypothesis that if developing stomatal initials occur too close to one another, initials will arrest. The results showed that arrested stomatal initials were not randomly placed, but were closely associated with another stoma, most often in an adjacent cell file. The distance to their nearest stomatal neighbors was less than the equivalent distance between stomata that mature. After stomatal initials form, their position within or across cell files was not adjusted by cell division or expansion. Synergistic effects from several neighboring stomata could not be linked to stomatal arrest; rather, arrest was associated only with the nearest stomatal neighbor. Since the arrest of stomatal initials was distance dependent, a failure intrinsic to the arrested initials is not solely responsible for halting stomatal development. These data show that an inhibitory mechanism adjusts stomatal development to influence the final distribution of Tradescantia stomata. The pigmentation and expansion characteristics of arrested stomatal initials were like those of epidermal cells, indicating that the initials did not remain halted at a specific point in their development. The capacity of arrested initials to differentiate in the epidermal cell pathway indicates that they remain pluripotent after their initial specification and that the opportunity for patterning is long enough to permit their entry into the epidermal cell pathway. PMID- 7883077 TI - Linear aggregations of stomata and epidermal cells in Tradescantia leaves: evidence for their group patterning as a function of the cell cycle. AB - We tested Charlton's hypothesis (1990) that stomata are present and patterned in linear cell aggregations using the monocot Tradescantia. We examined the following features of the leaf epidermis in support of this theory: linear groups (strings) of stomatal complexes and of epidermal cells were sought in immature and mature regions of entire leaves; the lengths (in cell number) and incidences (numerical occurrence) of both string types were determined; the uniformity and progression of stomatal differentiation within strings were studied; physical characteristics of differentiating strings within cell files were measured. Undifferentiated epidermal cells from the leaf base were stained with DAPI to reveal precursors of stomatal strings immediately proximal to the stomatal initial region. The results indicated that the Tradescantia epidermis in the leaf blade consists of linear groups of stomata and epidermal cells, which did not change in cell number nor incidence during development. The incidence of stomata by length was nonrandom. Although incidence decreased with string length, the decline was not linear nor exponential. Stomatal strings show cell cycle synchrony in DAPI staining of stomatal precursors and synchrony of stomatal differentiation within a string. The irregularity in the length of the stomatal development region, and each differentiation stage in it, by cell file was consistent with the variation in string length and unity in string development. The evidence supports Charlton's hypothesis that cells are patterned based on their position in the cell cycle and that linear groups of stomata reflect cell lineages, which maintain a degree of cell cycle synchrony. PMID- 7883078 TI - Ectopic TGF beta 1 expression in the secretory mammary epithelium induces early senescence of the epithelial stem cell population. AB - An important feature of the mammary gland is the regenerative capacity of its epithelium which is demonstrated upon successive cycles of lactation and involution. Pregnant mice expressing a whey-acidic protein (WAP) promoter-driven transforming growth factor-beta 1 (TGF beta 1) cDNA are unable either to generate a secretory mammary epithelium or to lactate. Here we investigate whether ectopic TGF beta 1 induces this phenotype by affecting the transgenic epithelium directly or in trans. Reciprocal transplantation of mammary tissue between normal and transgenic hosts resulted in the development of the respective phenotypes of the transplants within the same mammary fat pad. When isolated mammary epithelial cells from both were mixed before implantation so that transgenic and normal epithelium would develop together more proximately, both phenotypes were simultaneously observed in the resultant chimeric mammary outgrowths. Since no trans effect was detectable, we hypothesize that early expression of the transgene results in compromised lobular progenitor cells through an intracrine mechanism. Consistent with this posit, WAP promoter-driven protein expression was detected in individual cells of the subtending ducts of immature females at estrus. Transplantation of WAP-TGF beta 1 mammary gland into nonpregnant hosts revealed that transgenic implants, even those from young postpubertal virgin females, had a diminished ability to repopulate epithelium-free mammary fat pads. Accordingly, the ectopic expression of WAP-TGF beta 1 not only impairs lobular progenitors, but also promotes an early senescence of the regenerative capacity of the mammary ductal epithelium. This leads us to propose that mammary epithelial stem cells give rise to two functionally distinct progenitor cells in the mammary gland epithelium: one capable of producing daughters committed to ductal formation, the other capable only of producing daughters committed to lobular function. PMID- 7883079 TI - Molecular mechanisms of the activation of maturation-promoting factor during goldfish oocyte maturation. AB - Oocyte maturation is triggered by the activation in the oocyte cytoplasm of maturation-promoting factor (MPF), which consists of cdc2 (a catalytic subunit) and cyclin B (a regulatory subunit). Immature goldfish oocytes contain only inactive monomeric 35-kDa cdc2 and do not stockpile cyclin B. In maturing oocytes, activation of cdc2 is associated with its Thr161 phosphorylation and mobility shift on SDS-PAGE from 35 to 34 kDa after binding to cyclin B. Using mutant cdc2, we show that Thr161 phosphorylation is required for both the downward shift and the kinase activation. Since cdc2 Tyr15 is not phosphorylated after binding to cyclin B, it does not require dephosphorylation. This situation is obviously different from that in immature Xenopus oocytes, in which the cdc2 cyclin B complex preexists with cdc2 phosphorylated on both Tyr15 and Thr161, thereby requiring Tyr15 dephosphorylation catalyzed by cdc25 phosphatase for MPF activation. These results indicate that these species employ different mechanisms of MPF activation during oocyte maturation, although the final molecular structure of the active MPF (cdc2 bound to cyclin B and phosphorylated on Thr161) is identical. PMID- 7883080 TI - Biochemical evidence for cell fusion in placentas of mouse aggregation chimeras. AB - Eight series of mouse chimeras were produced by aggregating 8-cell embryos that differed at the Gpi-1s locus, encoding glucose phosphate isomerase (GPI-1). Chimeric blastocysts (Gpi-1sa/Gpi-1sa <--> Gpi-1sb/Gpi-1sb) were transferred to pseudopregnant females, which produced only GPI-1C enzyme. Quantitative electrophoresis of GPI-1 was used to estimate the contribution of each embryo (GPI-1A and GPI-1B enzyme activity) to the fetus and placentas of 12 1/2 day chimeric conceptuses. Chimeric fetuses and placentas were identified by the presence of both GPI-1AA and GPI-1BB homodimers. The overall distribution of the percentage GPI-1A in the placentas was bimodal or U-shaped. It was positively correlated with the %GPI-1A in the fetus in most of the eight series of chimeras analyzed. In the first chimera experiment, involving seven series of chimeras, GPI-1AB heteropolymer was detected in 78/211 (37%) of the placentas. Heteropolymer was not detected in chimeric placentas with an unbalanced composition of GPI-1A and GPI-1B. The production of heteropolymer implies that GPI-1A and GPI-1B monomers are produced in the same cell and that fusion must have occurred between the two genetically distinct cell populations in the placenta. In the second experiment, samples of different regions were dissected from another series of 27 chimeric placentas and analyzed; 12 contained heteropolymer. Although GPI-1AB heteropolymer was widely distributed throughout the placenta it was detected less frequently in the outer part of the placenta. In another experiment, analysis of 34 homozygous (nonchimeric) Gpi-1sb/Gpi-1sb conceptuses transferred to homozygous Gpi-1sa/Gpi-1sa reproductive tracts revealed no evidence for fusion between maternal cells and cells of zygotic origin in the placenta. The chimera studies provide biochemical evidence for fusion between zygotic cells in the murine placenta. This presumably occurs during the formation of the syncytial trophoblast. PMID- 7883081 TI - Secreted and membrane-bound isoforms of T1, an orphan receptor related to IL-1 binding proteins, are differently expressed in vivo. AB - The murine T1 gene encodes a membrane-bound glycoprotein (T1-M), highly similar to interleukin-1 (IL-1) receptor type I, and a soluble variant (T1-S) representing its isolated extracellular domain. In vivo, the expression pattern of both T1 isoforms differs drastically. The T1-M receptor is abundantly expressed in single cells of the major hemopoietic organs (embryonic liver, spleen, bone marrow). It is restricted to few hemopoietic cell types throughout ontogenesis. By contrast, the soluble T1-S protein is predominantly expressed in selected nonhemopoietic embryonic tissues (developing skin, bone, and retina) and deposited in extracellular matrix. Despite the similarity of the T1 ligand binding domain to all IL-1-binding proteins, it does not exhibit affinity to either IL-1 alpha or -beta. Thus, T1-M likely represents a novel orphan receptor of selected hemopoietic cells. The matrix-associated T1-S variant might act to create a reservoir of the putative T1 ligand in some differentiating tissues. PMID- 7883082 TI - Eyespot development on butterfly wings: the epidermal response to damage. AB - Eyespot colour patterns decorate the wings of many butterfly species. The eyespot is specified in the early pupal epidermis by signals from a central "focus," and it has been suggested that the focus is the source of a diffusible morphogen gradient. We show that ectopic eyespots can be induced in nonfocal positions throughout the distal, but not the proximal, wing epidermis of Bicyclus anynana by mild epidermal damage inflicted at 12-18 hr (into a 6- to 7-day pupal period). Damage may lower, locally and transiently, the threshold for response to morphogen. Here, we have tested two predictions of the gradient model. As predicted, mild damage close to the focus (parafocal) locally extends the eyespot, making it markedly asymmetrical, even after early operations (1 or 6 hr), when remote epidermis is non-responsive. Early parafocal operations also have an unexpected result, however, reducing the extent of the eyespot in other directions, perhaps through a long-range "wound effect" on the signaling activity of the focal cells. The model also correctly predicts that increasing the severity of a nonfocal operation will prolong the transient damage and hence give ectopic eyespots after early (1- or 6-hr) operations. We do not, however, find the expected size increase in ectopics induced by the later (12 or 18 hr) severe damage. Similarly, we demonstrate the predicted effect of early (1 or 6 hr) mild damage in increasing the response to a subsequent (18 hr) operation at the same position. The gradient model is therefore supported by most aspects of eyespot induction in response to epidermal damage. PMID- 7883083 TI - Human genetic polymorphisms. AB - Mutations in the human genome lead to genetic polymorphisms in the population. While many of these are considered to be normal variants, many lead to human disease and are usually maintained in the population by a balance between mutation and selection. The frequency and type of mutations have been determined for a number of loci in man. The frequency of mutation in transgenes is now receiving considerable attention, since proteins synthesized in recombinant DNA biological systems are subject to genetic alteration through mutation and selection. These changes can occur in the transgene, but mutations in the host cell genes can also produce structural modifications for example, by changes in post-translational modification. Mutation rates for human genes may be as high as 10(-5) per locus per generation. Spontaneous mutations that inactivate gene function in bacteria occur at a rate of 10(-5)-10(-6) per locus per generation. On the other hand the frequency of spontaneous mutations per nucleotide is two orders of magnitude less (usually less than 10(-7)). PMID- 7883085 TI - Mass spectrometry in the standardisation of recombinant products. PMID- 7883084 TI - A clinical evaluation of genetic stability. AB - Mutation in a genetically engineered cell line has not been shown to have been responsible for adverse clinical reactions in a currently licensed biotechnology product. There exists, however, the theoretical possibility that mutations in the production cell line could ultimately lead to patient exposure to aberrant proteins which could result in unanticipated or deleterious effects. The clinical trials of recombinant antihaemophilic factor, a large complex glycoprotein, which is administered chronically, offered a unique opportunity to explore this theoretical concern. In this retrospective analysis of patient data, evidence for unanticipated or adverse events which could possibly be attributed to mutations in the genetically engineered cell line was sought. Extensive analysis of a variety of patient data such as the efficacy, alterations in pharmacokinetic parameters, and inhibitor formation, gave no support for concern over host cell mutation. While this retrospective analysis cannot absolutely exclude the possibility of mutational events, those clinical data in combination with the product characterization information indicate that for this recombinant product, mutation is a highly improbable event. PMID- 7883086 TI - Genetic stability of protein expression systems in yeast. AB - For the expression of recombinant proteins in yeast, genetic stability is monitored using a combination of standard microbiology and nucleic acid testing procedures. Process consistency during the cell amplification and product expression phases of fermentation are also reliable indicators of stability. The potential for instability arising from point mutation, gene conversion or recombination has been shown to occur at a low frequency and does not generally affect protein product quality. PMID- 7883087 TI - Analytical strategies for the determination of protein modifications. AB - Assessment of recombinant protein product purity and consistency has been successfully accomplished by using a battery of quantitative analytical methods. The development of analytical methods for product control requires an understanding of potential changes in protein structure which could be caused by degradation and modification. This paper will review some of the common mechanisms of protein degradation and common modifications which can occur during the fermentation/cell culture and purification processes. It will also present examples of analytical techniques which have successfully elucidated some of these changes in protein structure. PMID- 7883088 TI - Use of biosensors to characterize recombinant proteins. AB - A new biosensor technology based on surface plasmon resonance (BIAcore, Pharmacia) is described which allows the surface and conformational integrity of a recombinant product to be monitored by measuring the binding characteristics of a panel of monoclonal antibodies. Interactions between the antibodies and the recombinant product are measured in real time in a quantitative and highly reproducible manner. This allows the association and dissociation kinetic rate constants of the antibodies to be calculated and not only the equilibrium binding constant. Besides using antibodies as conformational probes, the biosensor can also be used to measure directly the binding of a recombinant product to its natural biological ligand. Quantitative binding assays using biosensors are a powerful method for assessing the lot-to-lot consistency of recombinant products. PMID- 7883089 TI - Recombinant receptors as probes for the study of genetic stability. AB - Membrane receptors coupled to GTP binding G-proteins constitute one of the largest families of proteins involved in ligand binding, signal transmission and modulation of physiological effects. A large majority of current pharmaceuticals are actually ligands for this type of receptor, including e.g. the catecholamine, dopamine, serotonin and histamine antagonists. In recent years, an impressive number of the genes encoding these receptors have been cloned, sequenced and expressed in model cell lines. Molecular genetics has thus uncovered the existence of a surprisingly large number of homologous receptor subtypes each capable of binding the same natural ligand, but which may be distinguished on the basis of variable recognition patterns of synthetic ligand panels, variable expression during development and differentiation or different G-protein coupling and effector modulation. We have summarized in Table 1 some of the recently cloned receptors and have attempted to group them according to the type of ligand recognized: non peptidic, peptidic or other, including light and olfactory substances. Further information and references can be found in recent reviews. PMID- 7883090 TI - The role of bioassays in the assessment of recombinant proteins. AB - Although the need is diminishing, biological assays still have an important place in the characterization and quality control of therapeutic peptides prepared by recombinant DNA technology. This role needs to be assessed on a case-by-case, product-by-product basis. It includes as a minimum the need to establish during product development the range and quantitative nature of its biological activities, particularly those relevant to its intended clinical use and potential side effects. For those products whose quality and consistency can be established by alternative approaches, then a biological assay may no longer be necessary on a batch basis. For others, bioassays will be required until adequate and appropriate alternatives can be shown, through international collaborative studies, to be sufficient to assure the product's efficacy and safety in clinical use. So-called "bio-identity" tests are inappropriate and should not be used. PMID- 7883091 TI - New techniques in protein chemistry. PMID- 7883092 TI - Report on the Genetic Stability Symposium. April 10-12, 1991. West Coast Chapter, Parenteral Drug Association. PMID- 7883093 TI - Ensuring the consistency of rDNA-derived biologicals: the contribution of gene sequencing. AB - The past few years have seen an interesting debate on the extent to which DNA sequencing of expression systems is appropriate as a basis for assessing the quality and consistency of rDNA-derived products. While there is a need to improve and validate the ability of end-product testing procedures to detect low levels of variant proteins, there are several reasons why it may not be justified to require extensive DNA sequence analysis of large numbers of individual clones of producer cells. These include difficulties in interpreting the resultant data due to artefacts introduced by PCR and the fact that other events, such as translational errors and chemical and enzymic alterations during production and downstream processing, also lead to potential heterogeneity of pharmaceutical proteins. The evaluation of these products can only be made at the protein level. Some DNA sequencing will be required during product development, but in practice the quality and consistency of rDNA-derived products are best determined by a range of in-process and end-product testing procedures, including the use of biological assays and standardization. PMID- 7883094 TI - Genetic stability and product consistency of rDNA-derived biologicals from mammalian cells. PMID- 7883095 TI - Translational errors during recombinant protein synthesis. AB - Cloned human genes can now be readily expressed in organisms like Escherichia coli (E. coli) and fungi and this has made recombinant human proteins available for use in clinical medicine. Expressing foreign proteins at high rates to make them major cell components can, however, lead to nutritional stresses in the production cells. Such stresses markedly increase the frequency of random translational errors, both in model laboratory experiments and in actual fermentations. The burden of detecting and removing errors then falls on the purification processes. Random errors are, however, difficult to detect as they will produce a heterogeneous mixture of polypeptides. Each type of altered protein may be present in quite small amounts but the total number of erroneous molecules could be substantial. Little is known about how erroneous proteins could affect patients and much more information is needed to clarify this problem. Techniques for limiting and monitoring translational errors are briefly discussed. PMID- 7883096 TI - Assessing genetic stability at the nucleic acid level. AB - Due to the natural genetic instability of any living organisms as well as faulty amino acid incorporation by the translational machinery or by post-processing alteration, a recombinant protein is prone to contamination at various levels by mutated or altered molecules. However, it should be borne in mind that alteration at the nucleic acid level will be amplified and may affect a substantial percentage of the whole population, while alterations introduced at the protein level are not further amplified and will at the most constitute a harmless background. While it is the protein and not the gene that is used as a medicine, it is important to recognize that analytical results obtained at the protein level are better interpreted when they are backed by good knowledge of the genetic system. Direct sequencing of a gene borne by a plasmid or of a reverse transcriptase-polymerase chain reaction (RT PCR) product can provide the sequence of the majority of the molecules. However, it fails to detect mutated molecules corresponding to a low level of contaminant. Therefore, a statistical treatment of the polymorphism of the population or the use of alternative methods such as those based on single-strand conformational polymorphism (SSCP) or chemical cleavage modification (CCM) are recommended. PMID- 7883097 TI - Genetic stability and recombinant product consistency. PMID- 7883098 TI - Genetic and phenotypic markers and their relationship to product quality and consistency. AB - Manufacturers of products derived from biological systems have long sought to identify relevant genotypic and phenotypic markers displayed by production strains and cell lines which could be employed as in-process monitors to predict product quality. Ideally, changes in these markers would signal possible changes in product quality and could be used to ensure batch to batch product consistency. In mammalian cell culture-based manufacturing processes, individual cell lines can exhibit varying genotypes and phenotypes, not all of which are relevant to cellular protein synthesis. In this paper we present data illustrating that two key phenotypic markers, thought to be relevant to protein biosynthesis (specific growth rate and cellular productivity), can vary significantly without causing obvious changes in product characteristics. Additionally, we outline our approach to genotypic characterization at the cell bank and post-process stages and our rationale for this approach. PMID- 7883099 TI - Consistency and stability of recombinant fermentations. AB - Production of proteins of consistent quality in heterologous, genetically engineered expression systems is dependent upon identifying the manufacturing process parameters which have an impact on product structure, function, or purity, validating acceptable ranges for these variables, and performing the manufacturing process as specified. One of the factors which may affect product consistency is genetic instability of the primary product sequence, as well as instability of genes which code for proteins responsible for post-translational modification of the product. Approaches have been developed for mammalian expression systems to assure that product quality is not changing through mechanisms of genetic instability. Sensitive protein analytical methods, particularly peptide mapping, are used to evaluate product structure directly, and are more sensitive in detecting genetic instability than is direct genetic analysis by nucleotide sequencing of the recombinant gene or mRNA. These methods are being employed to demonstrate that the manufacturing process consistently yields a product of defined structure from cells cultured through the range of cell ages used in the manufacturing process and well beyond the maximum cell age defined for the process. The combination of well designed validation studies which demonstrate consistent product quality as a function of cell age, and rigorous quality control of every product lot by sensitive protein analytical methods provide the necessary assurance that product structure is not being altered through mechanisms of mutation and selection. PMID- 7883100 TI - Gene stability in mammalian cells and protein consistency. AB - The safety of a patient who is the recipient of protein drugs has to be assured. A "wrong" protein is thought to represent a great risk. The philosophy of testing strategies related to gene stability with product safety will be discussed in the light of experimental data available today. Although all mammalian cell lines used in the production of biologicals including recombinant DNA-derived lines have been produced from individual clones (functional monoclonality) they have been found to be heterogenous with regard to the genomic content (number of chromosomes, characteristics of identifiable chromosomes and position and number of integrated recombinant sequences). The verification of the presence of correct gene in a production cell line constitutes a well accepted and useful test, especially if derived by "population sequencing". A batch not related repeated confirmation of this fact cannot lead to any additional assurance for the correctness of all proteins constituting a given product beyond the level provided by cheminal testing. In contrast to this obvious and unavoidable heterogeneity in cellular genomes, the coding regions of genes have not been shown to change. Evidence is available to demonstrate the consistency of protein products originating from recombinant (and hybridoma) cell lines, e.g. more than 500,000 patients have received and tolerated rtPA well. PMID- 7883101 TI - The origins and consequences of genetic instability in prokaryotes. AB - The causes of genetic change include errors in replication and repair, transposition and recombination. Together, these processes generate a reservoir of genetic variants from which selection will amplify any changes which increase host fitness. Recombination, transposition and slippage during replication may all result in large-scale DNA rearrangements. Homologous and illegitimate recombination generate deletions, inversions, duplications and fusions. Intramolecular transposition can cause deletion or inversion of DNA sequences adjacent to the mobile element, while intermolecular movement may lead to fusion of donor and target replicons when transposition is replicative. Of crucial importance is how genetic variation affects the fitness of the host cell. For a neutral variant the probability of eventual fixation is small, but changes which increase host cell fitness pose a more serious problem because these cells will eventually dominate the culture. The most effective way to combat the proliferation of variant plasmid cloning vectors is to block the processes by which they arise. Cloning vectors should be "stress-tested" and DNA sequence analysis programs can be used to screen for sequence repetition which should be removed, as far as possible, from both vectors and cloned sequences. It is also important that vectors place modest metabolic demands on their hosts in order to minimise the potential increase in fitness associated with changes in plasmid structure. PMID- 7883102 TI - Polymerase chain reaction (PCR) and sequencing. AB - For sequence analysis of transfected genes there are two approaches which can be adopted. One is to derive a consensus sequence of the gene in question and this may, in addition to providing the basic sequence, provide limited information on the presence of variant sequences. In order to provide more extensive data on variant sequences a second approach has to be adopted and that is to subclone the transfected gene (or mRNA) and analyse the sequences of large numbers of the subclones. While there are few obstacles nowadays to deriving a consensus sequence, considerable care has to be exercised in interpreting sequence data derived after subcloning because of the possible introduction of laboratory artefacts. PMID- 7883103 TI - Use of polymerase chain reaction (PCR) in the development of a recombinant organism. AB - Tryptic mapping of a purified recombinant antibody expressed in a mammalian cell line demonstrated low level heterogeneity in the heavy chain. Amino acid analysis and N-terminal sequencing of these fragments revealed that a conversion of tyrosine (Y) to glutamine (Q) had occurred at residue 376. DNA sequencing of 30 clones of the original expression construct indicated that the chance of the Y376Q variant being present in the original plasmid was low, < 5%. Once the gene had been cloned into a mammalian cell system, sequencing of 30 clones is considered ineffective for screening large numbers of subclones. Consequently, an alternative method was developed to directly probe total mammalian DNA for the presence of cloned variant. The method described here uses a polymerase chain reaction (PCR) based assay optimizing the ability of Taq polymerase to distinguish whether the 3' end of primers have completely annealed with template DNA during PCR cycling. Ten percent of the subclones producing high levels of the variant were identified and experiments indicated that the Y to Q conversion had developed during transfection of the antibody gene into the mammalian cell system. PCR was shown to be useful as a quick screen for verification of a cloned variant. Tryptic mapping is still considered the most sensitive and appropriate analytical tool for assessing genetic heterogeneity of recombinant cell lines. PMID- 7883104 TI - Genetic stability of rDNA production systems, a case report. AB - Producing rDNA proteins to be used as human therapeutic agents requires a biological production system during both storage and growth. The genetic make-up of a biological system is usually known through the laboratory history of the host strain and the process of vector construction. All master cell banks prepared for the production of medicinal products are fully characterized at the genetic and biochemical level. Whether these characteristics can be consistently maintained, particularly when the cells are propagated through a high number of generations and the culture grown into tens of thousands of litres, will have significant effects on the quality of the final products. Considerable experience and data regarding the stability of biological production systems involving plasmid and E. coli or yeast have been accumulated during the past 10 years. These data, including size and restriction analyses of the plasmid and sequence determination of relevant portions of the plasmid DNA isolated from cells collected before culture harvest, demonstrated that plasmid alteration at the structural level do occur, and some with high frequency or concentration. Assisted by such genetic information, criteria for accepting or rejecting a fermentation run can be established. PMID- 7883105 TI - The limitations of nucleic acid testing. PMID- 7883106 TI - Cocaine alters cyclic motor activity in the fetal rat. AB - Individual rat fetuses were exposed to cocaine by injection into the cisterna magna on E20 or E21 of gestation. On E20, cocaine elevated motor activity throughout the 20-min session, with activity increasing to double SAL-injected levels by the end of the session. On E21, overall activity also was elevated after cocaine, increasing four- to fivefold in the first 5 min of the session, and decreasing to twice the levels of SAL controls thereafter. Movement time series were subjected to spectral analysis to characterize cyclic motor organization. Cyclicity was evident in 67% of control and 97% of cocaine-injected fetuses. Cocaine increased the number of peaks in the movement spectrum and resulted in greater spectral density at the primary frequency of cyclic movement. Prenatal exposure to cocaine may alter patterns of cyclicity in the fetus, with consequences for the normal development of attention and behavioral state in the neonate. PMID- 7883107 TI - Potentiation of isolation-induced vocalization by brief exposure of rat pups to maternal cues. AB - Since their discovery in 1956, the highest rates of ultrasonic vocalization (USV) have been recorded from infant rats when first isolated in an unfamiliar place. We now report that peak USV rates can be doubled by allowing test pups a brief initial period of contact with their anesthetized dam (1-10 min) in the test chamber before isolating the pup by her removal. Potentiation of the isolation response was specific to the dam, for it failed to occur following initial contact with a group of 4 warm, anesthetized littermates. Control experiments showed that potentiation could not be attributed to thermal contrast, experimenter handling, general behavioral activation, novelty of maternal cues, or nursing deprivation. Furthermore, it did not occur when pups were taken for isolation testing directly from prolonged contact with their anesthetized dam in the home cage. Potentiation may be understood in terms of the communicative role of the pups' call and/or prior learning contingencies within the mother-infant interaction. PMID- 7883108 TI - Sound localization in newborn human infants. AB - Newborns' localization of sounds was examined in two experiments that utilized different psychophysical procedures and imposed different task demands. The results of both experiments were consistent in indicating that neonates not only differentiate the hemifield of a sound source but have some capacity to localize a sound within the hemifields. Adjustment of their initial head turn angle following a within-hemifield shift in location of an ongoing sound indicated that head orientation in neonates is elicited not only by sound onset but also by changes in location of an ongoing sound. Thus, multiple stimulus parameters impact on this neonatal response. Results are related to research on sound localization in older infants, and discussed in light of early development of the central auditory system. PMID- 7883109 TI - Dynamics of beta-cell mass in the growing rat pancreas. Estimation with a simple mathematical model. AB - The growth and development of the endocrine pancreas has been studied for many years, but questions remain concerning the regulation of the mass of insulin producing beta-cells both in the normal growing pancreas and during the pathogenesis of diabetes. The homeostatic control of beta-cell mass in both normal and pathophysiological conditions is based on the balance of cell proliferation, cell growth, and cell death. To gain insight into the relative contribution of each of these dynamic processes, we first mathematically analyzed the data available on the components involved in the maintenance of beta-cell mass, including rates of replication, beta-cell volume, and the beta-cell mass itself, at various ages in normal Sprague-Dawley rats. Then these data were combined in a simple mass balance equation to construct a mathematical model of the dynamics of the beta-cell mass in the normal growing rat pancreas. Such a model has allowed us to infer the contributions of fluxes that cannot be measured, i.e., neogenesis and cell death, to the known mass of beta-cells. Another important contribution of this model is to raise unanswered questions concerning the control of the balance of cell death and cell renewal in the endocrine pancreas. PMID- 7883110 TI - Human insulin in hypoglycemia. A new arena? PMID- 7883111 TI - Rate of weight gain, weight fluctuation, and incidence of NIDDM. AB - The relationships of rate of weight gain and weight fluctuation to incidence of non-insulin-dependent diabetes mellitus (NIDDM) were examined in Pima Indians. The 1,458 subjects were participants in a prospective study with examinations approximately every 2 years. Rate of weight gain was defined as the slope of the regression line of weight with time for two or more consecutive examinations > or = 2 years apart and weight fluctuation as the root-mean-square departure from this line for four examinations. Among men, incidence of NIDDM was strongly and significantly related to rate of weight gain (e.g., age-adjusted incidence = 56.7/1,000 person-years in those with weight gain > or = 3 kg/year and 16.9/1,000 person-years for those losing weight [Ptrend < 0.01]). In women, weight gain was significantly related to diabetes incidence only in those who were not initially overweight (body mass index < 27.3 kg/m2). In contrast to the relationship with weight gain, weight fluctuation was not associated with incidence of diabetes in either sex. These findings suggest that weight control in overweight individuals may be a more effective strategy for prevention of NIDDM in men than in women, whereas prevention of obesity may prevent diabetes in both sexes. Concern about a diabetogenic effect of weight fluctuation should not deter weight-control efforts. PMID- 7883112 TI - Insulin inhibits liver expression of the CCAAT/enhancer-binding protein beta. AB - The CCAAT/enhancer-binding protein beta (C/EBP beta) is a transcription factor that is abundant in the liver. The concentration of C/EBP beta mRNA in the liver of mice and rats fed a high-carbohydrate diet, which causes a rise in blood insulin levels, was lower (80 and 65%, respectively) than that detected in animals fed a standard diet. Similarly, the expression of the human insulin gene in the liver of transgenic mice led to a decrease in the concentration of C/EBP beta mRNA. However, no change was detected in the mRNA levels of C/EBP alpha or cAMP regulatory element-binding protein transcription factors in the livers of these mice. Furthermore, the expression of the C/EBP beta gene increased in the liver of diabetic rats and decreased in the liver of diabetic animals treated with vanadate, an insulin mimetic agent. In addition, a decrease in C/EBP beta protein was observed in liver nuclei from mice after insulin injections, in mice fed a high-carbohydrate diet, and in transgenic mice expressing the insulin gene in the liver. These results suggest that insulin might control gene expression in vivo, at least in part, by a mechanism involving a decrease in the transcription factor C/EBP beta. PMID- 7883113 TI - Differential effects of human and animal insulin on the responses to hypoglycemia in elderly patients with NIDDM. AB - Recent studies suggest that insulin-dependent diabetes mellitus patients switched from animal to human insulin may have decreased awareness of hypoglycemic warning symptoms. The risk of severe or fatal hypoglycemia associated with the treatment of diabetes increases with age. We conducted these studies to determine if awareness of hypoglycemic warning symptoms was greater with animal than with human insulin in elderly patients with diabetes. Nonobese elderly patients with non-insulin-dependent diabetes mellitus (NIDDM) (n = 13; age, 74 +/- 1 years; body mass index, 26.6 +/- 0.7 kg/m2) underwent paired hyperinsulinemic glucose clamp studies (insulin infusion rate 60 mU.m-2.min) in random order. In one study, regular human insulin was infused, and in the other study, regular beef/pork insulin was infused. In all studies, plasma glucose was decreased from fasting levels to 5 mmol/l during the first 60 min and was then allowed to fall to 4.4, 3.8, 3.3, and 2.8 mmol/l in each subsequent hour. Subjects were blinded as to which study they were undergoing. In each study, a hypoglycemic symptom checklist was administered, and counterregulatory hormones were measured every 15 min. Neuropsychological tests were performed every hour. Counterregulatory hormone responses to the two insulin preparations were similar. Autonomic (P < 0.05) and neuroglycopenic (P < 0.01) symptom scores were significantly higher during the beef/pork insulin studies. The responses on the neuropsychological tests were not significantly different. We conclude that beef/pork insulin results in greater awareness of hypoglycemic warning symptoms than does human insulin in elderly patients with NIDDM. PMID- 7883114 TI - T-cell reactivity to beta-cell membrane antigens associated with beta-cell destruction in IDDM. AB - Insulin-dependent diabetes mellitus (IDDM) results from a T-cell-mediated destruction of the insulin-producing beta-cells. In this study, we designed a sensitive assay to detect and identify islet cell-reactive T-cells in patients with newly diagnosed IDDM. The relation between T-cell recognition of beta-cell antigens with IDDM and the pathogenesis of the disease (the beta-cell destruction process) was tested in a large group of IDDM patients and compared with T-cell responses in nondiabetic children with other chronic inflammations and in immunologically normal, age-matched control subjects. The results demonstrate that peripheral blood T-cells reacting with a beta-cell membrane preparation enriched for insulin-secretory granule antigen were detectable in the majority of newly diagnosed IDDM patients (27 of 40 [67%]; mean stimulation index [SI] 37.0). Such reactivity was reduced postonset in IDDM patients proportionally to the duration of the disease (11 of 30 [37%]; mean SI 8.7). Nondiabetic age-matched control subjects showed no responses or moderate responses to the granule preparation (4 of 48 [8%]; mean SI 3.4). The magnitude of the T-cell response was significantly greater in newly diagnosed IDDM patients than in IDDM patients tested at least 2 years postonset (P < 0.001). Two children in remission for insulin dependency (so-called honeymoon period) displayed exceptionally high proliferative responses to insulin-secretory granules (mean SI 86.7). These results imply that T-cell recognition of insulin-secretory granule antigens is associated with IDDM and in particular with the immune-mediated process of beta cell destruction. PMID- 7883116 TI - Human hexokinase II mRNA and gene structure. AB - This study reports the isolation and characterization of the human hexokinase II (HKII) gene. This gene is approximately 50 kilobases in length and contains 18 exons, ranging in size from 96 to 2,536 base pairs, that are exactly the same size as the corresponding exons in the rat HKII gene. A cDNA representing the entire open reading frame for HKII was synthesized using a series of polymerase chain reactions with human skeletal muscle RNA as the template, and this allowed us to deduce the complete structure of the HKII mRNA. The human HKII mRNA has 431 nucleotides (nt) of 5' noncoding sequence, 2,751 nt of coding sequence, and 2,394 nt of 3' noncoding sequence. The open reading frame encodes a protein of 917 amino acids with an estimated molecular mass of 102.4 kDa. There is a high degree of similarity in the amino acid and nt sequences of the rat and human glucokinase and HKII proteins and genes. This, coupled with the observation that the exon sizes are conserved, suggests a common evolutionary origin of the these two genes. PMID- 7883115 TI - Evidence for a major gene affecting postchallenge insulin levels in Mexican Americans. AB - Hyperinsulinemia, which is considered a hallmark of insulin resistance, precedes the development of non-insulin-dependent diabetes mellitus (NIDDM). Results of family and twin studies have shown that heredity influences insulin resistance and insulin levels. In Caucasian families ascertained through two or more NIDDM siblings, it has been reported that single genes with large effects, i.e., major genes, influence both fasting and 1-h postchallenge insulin levels. To determine whether a major gene affects 2-h postchallenge insulin levels in Mexican Americans, we conducted segregation analyses using data collected on 527 pedigreed individuals from 27 families in San Antonio, TX. Probands for the families were randomly ascertained and all first-, second-, and third-degree relatives aged 16 years and older were invited to participate. Subjects received a 2-h oral glucose tolerance test, and diabetes was diagnosed according to World Health Organization criteria. We found that an autosomal dominant major gene best described the inheritance of 2-h insulin levels (ln-transformed) in these 27 families. Of the individuals in the population, 17% were homozygous for the 2-h low-insulin allele (back-transformed mean = 125 pmol/l) and 83% were heterozygous or homozygous for the 2-h high-insulin allele (back-transformed mean = 406 pmol/l). This major gene accounted for 31% of the variance in ln(2-h insulin levels) in this population. Using quantitative trait linkage analyses, we excluded tight linkage between this gene affecting 2-h insulin levels and three candidate loci for insulin levels: the insulin receptor gene, the low-density lipoprotein receptor gene, and the glucokinase gene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883117 TI - Factors modifying the risk of IDDM in offspring of an IDDM parent. AB - Offspring of mothers with insulin-dependent diabetes mellitus (IDDM) have a much lower risk of IDDM than do offspring of diabetic fathers, and this risk is particularly low for offspring born to diabetic mothers over the age of 25 years. To determine whether increasing maternal age also protects the offspring of IDDM fathers from IDDM, we surveyed 367 IDDM fathers (IDDM onset before age 35) who first came to the Joslin Clinic (Boston, MA) between 1945 and 1969. Of the 840 offspring of these men, IDDM developed in 28 before the age of 20, giving a cumulative risk of 5.1 +/- 1.0% (means +/- SE). Because this is similar to the result of our earlier study of IDDM fathers, the two groups were combined to give 1,084 offspring, 39 having IDDM (cumulative risk of IDDM 5.4 +/- 0.9% by age 20), for comparison with our cohort of 1,391 offspring of 739 IDDM mothers. In that cohort, IDDM developed in 20 offspring before the age of 20 years, giving a cumulative risk of 2.1 +/- 0.5%. The risk of diabetes in offspring was higher if the parent's IDDM was diagnosed before age 11 than if it was diagnosed later: 9.3 compared with 4.0% (P = 0.006) for the offspring of IDDM fathers and 2.7 compared with 1.8% for the offspring of IDDM mothers (P = 0.06). In the families in which the father's IDDM was diagnosed after age 11, a protective effect of maternal age > or = 25, similar to that in families of IDDM mothers, seems to be present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883118 TI - Slow [Ca2+]i oscillations induced by ketoisocaproate in single mouse pancreatic islets. AB - The effect of alpha-ketoisocaproate (KIC), the first catabolic metabolite of the amino acid leucine, on [Ca2+]i, insulin release, and membrane potential was measured in mouse pancreatic islets of Langerhans. Stimulatory concentrations of KIC (2.5-10 mmol/l) caused slow oscillations of [Ca2+]i and cyclic variations of the membrane potential. Slow [Ca2+]i oscillations depended on extracellular calcium. Simultaneous measurements of [Ca2+]i and insulin release resolved pulsatile insulin secretion that paralleled slow [Ca2+]i oscillations. Whereas 11 mmol/l glucose induced a significant increase in cAMP, KIC was unable to modify it. Glucagon (10 nmol/l), which significantly increased cAMP in mouse islets, also increased the frequency of glucose-induced fast [Ca2+]i oscillations. However, neither glucagon (10 nmol/l) nor dibutyryl cAMP (1 mmol/l) was able to change the slow oscillation pattern into a fast pattern. Imaging of Ca2+ showed that KIC-induced slow oscillations were synchronic throughout the whole islet. It is suggested that beta-cell electrical activity plays a role in the origin of slow [Ca2+]i oscillations. PMID- 7883119 TI - Regulation of glycogen synthase by glucose, glucosamine, and glutamine:fructose-6 phosphate amidotransferase. AB - The hexosamine biosynthesis pathway has been hypothesized to mediate some of the regulatory as well as the deleterious effects of glucose. We have stably overexpressed the cDNA for human glutamine:fructose-6-phosphate amidotransferase (GFA), the rate-limiting enzyme in the hexosamine biosynthesis pathway, in rat-1 fibroblasts. Two cell lines expressing the human RNA were selected by Northern analysis, and they exhibited 51-95% increases in GFA activity. Insulin-stimulated glycogen synthase (GS) activity and net glycogen synthesis were assayed, and GFA cells revealed decreased insulin sensitivity for both GS and net glycogen synthesis. The ED50 for insulin stimulation of GS was 2.45 +/- 0.4 nmol/l insulin in controls and 5.29 +/- 1.01 nmol/l in GFA cells (P < 0.005). For insulin stimulated glycogen synthesis, the ED50 was 3.43 +/- 0.88 nmol/l in controls and 5.54 +/- 0.98 nmol/l in GFA cells (P < 0.005). There were no significant differences in maximally insulin-stimulated or total GS activities, insulin binding or receptor number, or glucose uptake between GFA and control cells. We also examined the effects of glucose on GS activity. GFA cells had a twofold increase in GS activity at low glucose (0.5 mmol/l) when compared with controls (P < 0.025). Both GFA and control cells had an approximately 75-80% decrease in GS activity as glucose concentration was increased from 0.5 to 20 mmol/l. This change in GS activity was not observed until after 12 h in culture. GFA cells were more sensitive to the effects of glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883120 TI - Amino acid substitutions in hexokinase II among patients with NIDDM. AB - Hexokinase (HK) II plays an important role in intracellular glucose metabolism by catalyzing the conversion of glucose to glucose-6-phosphate. HKII is considered to be a promising candidate gene for non-insulin-dependent diabetes mellitus (NIDDM) and insulin resistance. Therefore, we investigated the frequency of variants in the coding region of the HKII gene in patients with NIDDM. Initial screening included a population-based sample of 40 Finnish patients with typical NIDDM, and subsequent screening included an additional 72 patients with NIDDM. By applying single-strand conformation polymorphism analysis and direct sequencing, the following amino acid substitutions were found among the 112 NIDDM patients: Ala314Val in one patient (0.9%), Arg353Cys in three patients (2.7%), and Arg775Gln substitution in three patients (2.7%). We also screened 97 subjects with completely normal glucose tolerance and a negative family history of diabetes for these mutations. The Ala314Val and the Arg353Cys substitutions were not found in control subjects, but the Arg775Gln substitution was found in two (2.1%) control subjects. None of these mutations were located close to the glucose- and ATP-binding sites of HKII. We conclude that mutations of the HKII gene are not a major etiological factor for NIDDM in the Finnish population. PMID- 7883121 TI - Role for transforming growth factor beta in thromboxane-induced increases in mesangial cell fibronectin synthesis. AB - Thromboxane A2 (TXA2) has been implicated in the pathogenesis of progressive glomerulosclerosis and stimulates the synthesis of matrix protein by mesangial cells (MCs). This study examined the role of transforming growth factor beta (TGF beta) in the mediation of the action of the stable TXA2/prostaglandin (PG) endoperoxide analog U-46619 to stimulate fibronectin (Fn) synthesis in cultured rat MC. Exogenous TGF-beta increased Fn synthesis by MC in a concentration- and time-dependent fashion, as reflected by incorporation of [35S]methionine into immunoprecipitable Fn. Submaximal concentrations of TGF-beta (1-2.5 pmol/l) increased Fn synthesis two- to threefold, a response comparable in magnitude to that observed with a maximal stimulatory concentration (1 mumol/l) of U-46619. Anti-TGF-beta antibody, but not isotypic IgG, blocked the increases in Fn synthesis induced by both U-46619 and exogenous TGF-beta. Endogenous TGF-beta bioactivity in MC culture media, assessed by the mink lung epithelial cell system, was significantly increased by 1 mumol/l U-46619 (1.7 +/- 0.3 pmol/l) compared with that of control media (0.6 +/- 0.1 pmol/l, P < 0.05). Total (active plus latent) TGF-beta bioactivity, assayed after heat activation of latent TGF beta, was also significantly higher in media of MCs cultured with U-46619 (45 +/- 4 pmol/l) compared with control (24 +/- 4 pmol/l). Thus, U-46619 increased endogenous TGF-beta bioactivity to a level sufficient to account for the enhancement of Fn synthesis observed with U-46619, as reflected by the Fn synthetic response to exogenous TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883122 TI - Analysis of the hexokinase II gene in subjects with insulin resistance and NIDDM and detection of a Gln142-->His substitution. AB - Hexokinase II (HKII) is the predominant hexokinase isozyme expressed in insulin responsive tissues. Since defects involving glucose transport and/or its phosphorylation to glucose-6-phosphate are present in muscle of insulin-resistant humans, HKII should be viewed as a candidate gene for inherited insulin resistance and susceptibility to non-insulin-dependent diabetes mellitus (NIDDM). To investigate the prevalence of potential mutations in the gene encoding HKII, we used the polymerase chain reaction (PCR) to amplify each of the 18 exons of the HKII gene from genomic DNA derived from 59 subjects: 25 insulin-resistant probands with clinical features of the type A syndrome and 34 NIDDM subjects enrolled in the United Kingdom Prospective Study of Therapies of NIDDM (UKPDS) who represented the highest percentile of fasting hyperinsulinemia in the UKPDS population of 5,098 subjects. PCR products corresponding to individual HKII exons derived from each subject were screened for the presence of nucleotide variation using a sensitive nonradioactive single-strand conformation polymorphism (SSCP) protocol. Variant SSCP patterns indicative of genetic variation were detected only in PCR amplimers containing exons 4-7, 10, 15, and 17. Direct sequencing of amplified DNA from individuals affected with variant SSCP patterns revealed the presence of the following silent polymorphisms: Asp251 (GAT/C) in exon 7 and Asn692 (AAT/C) in exon 15. SSCP variants detected in PCR products containing exons 5, 10, and 17 were due to single base substitutions in flanking intronic sequences. A polymorphic GGA repeat was identified within intron 5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883123 TI - Identification of four amino acid substitutions in hexokinase II and studies of relationships to NIDDM, glucose effectiveness, and insulin sensitivity. AB - Human hexokinase (HK) II, a glucose phosphorylating enzyme in muscle tissue, plays a central role in glucose metabolism. Since reduced insulin-stimulated glucose uptake and reduced glucose-6-phosphate content in muscle have been demonstrated in pre-non-insulin-dependent diabetes mellitus (pre-NIDDM) and NIDDM subjects, we have examined the coding region of the HKII gene in NIDDM patients to determine whether these patients show genetic polymorphisms that are associated with or contribute to the disease. Single-strand conformational polymorphism analysis and nucleotide sequencing were initially performed on the entire coding region of the HKII gene of 38 insulin-resistant NIDDM patients and 5 healthy control subjects. This analysis revealed four missense mutations at codons 142 (Gln to His), 148 (Leu to Phe), 497 (Arg to Gln), and 844 (Arg to Lys) and an additional six exon polymorphisms that did not predict any change in amino acid composition of the protein. One homozygous and nine heterozygous carriers of the codon 142 mutation were found among the NIDDM patients. The mutations at codons 148, 497, and 844 were each found in one diabetic subject and only on one allele. There were no carriers of compound heterozygous mutations. A subsequent study of 301 patients with NIDDM and 151 healthy control subjects revealed no additional mutations at codons 148, 497, or 844. The total frequency of the mutated allele at codon 142 was 18.9% among the control subjects and 17.0% among the NIDDM patients (chi 2 = 0.56, P = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883124 TI - Diabetes induced with low doses of streptozotocin is mediated by V beta 8.2+ T cells. AB - T-cells have been shown to cause insulitis and ultimately be responsible for the destruction of beta-cells in animal models of insulin-dependent diabetes mellitus (IDDM). In one murine model, insulitis and hyperglycemia occur after administration of five low doses of streptozotocin (STZ) (multidose STZ-induced diabetes mellitus [MDSM]). Insulitis can first be identified in the islets after the final (fifth) daily dose of STZ is given. We have studied the T-cells that infiltrate the islets of Langerhans during the early stages of diabetes by preparing Southern blots of T-cell receptor (TCR) beta-chain genes amplified by polymerase chain reaction (PCR) from islets from C57BL/KsJ mice given multiple doses of STZ. The relative abundance of TCR gene products in islets was compared with spleen cells stimulated with anti-CD3 monoclonal antibody (mAb). We found that after the fourth dose of STZ, there was a striking increase in the amount of V beta 8.2 TCR gene product (37 +/- 4% of total PCR signal) compared with T-cells in the spleen (9 +/- 2%, P < 0.01), which increased further 2 days after the final dose of STZ (47 +/- 5%, P < 0.001). We studied the heterogeneity of the size of the V beta 8.2 TCR CDR3 region and found primarily products with only two lengths compared with a heterogeneous population in the spleen. Treatment with anti-V beta 8 mAb, but not anti-V beta 9 and anti-V beta 13 mAbs, prevented development of hyperglycemia (P < 0.0001) and insulitis (P < 0.0005) after STZ administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883125 TI - [Coronary angioplasty in an Italian hospital without on-site cardiac surgery: the results and outlook]. AB - BACKGROUND: The concept of the absolute need of surgical standby for coronary angioplasty, although still strongly supported by the Task Force of the AHA and ACC, has been changing over the years according to the developments of PTCA equipment and the introduction of autoperfusion balloon catheters and coronary stents. In many European countries and in Canada, due to the relative lack of institutions performing cardiac surgery, almost 40% of cardiac laboratories are now performing PTCA without on-site surgical standby. METHODS AND RESULTS: Following a previous experience in another institution with on-site cardiac surgery, since January 1991 until February 1994, 742 Patients underwent PTCA in our Hospital not provided with on-site cardiac surgery. Surgical standby was requested in 99 cases to nearby surgical centers and it was utilized in 6 cases. Primary success was achieved in 91% of stenoses (94% in non occlusive and 69% in totally occlusive lesions). The mortality rate in cases other than cardiogenic shock was 0.13%, the myocardial infarction rate was 1.2% and the rate of emergency coronary bypass operation was 0.8%. CONCLUSIONS: PTCA in our view, as well as others', can be successfully performed in Institutions without on-site surgical support, provided the cardiac team has achieved a satisfactory experience and skill, the correct equipment for treatment of occlusive complications is available and a nearby surgical institution is alerted for procedures considered at particular risk, due to the amount of myocardium in jeopardy in case of irreversible arterial occlusion. PMID- 7883126 TI - [Coronary angioplasty and surgical standby : an open problem]. PMID- 7883127 TI - [The ECCIS study: the epidemiology and clinical picture of silent ischemic cardiopathy. Epidemiologia e Clinica della Cardiopatia Ischemica Silente]. AB - BACKGROUND: The ECCIS project (Epidemiology and Clinic of Silent Ischemic Heart Disease) is an italian epidemiological study based on a population sample of 4,842 totally asymptomatic men aged 40-59 whose primary aim is the evaluation of the prevalence of totally silent myocardial ischemia and silent myocardial infarction. METHODS: The systemic search for markers of silent ischemia and infarction was pursued along 3 screening stages: the 1st stage included resting electrocardiogram, hyperventilation test, exercise electrocardiogram and 24-hour Holter electrocardiogram; the 2nd stage included echocardiogram, thallium-201 scintigraphy in conjunction with exercise test or dypiridamole test, exercise radionuclide ventriculography and ergometrine test; the 3rd stage included coronary angiography. After the completion of the 1st stage procedures 439 men (9.1%) with abnormal results and low probability of disease were invited to the 2nd stage and 387 accepted to undergo the diagnostic procedures. After the completion of the 2nd stage, 104 men with moderate or high suspicion of silent myocardial ischemia or infarction were invited to perform coronary angiography but only 62 men accepted to undergo the 3rd stage procedures (participation rate 59.6%). RESULTS: The final diagnosis of totally silent myocardial ischemia or infarction on the basis of predefined criteria was established in 25 patients. The prevalence of silent ischemic heart disease on the overall original 4,842 men was 0.52% (95% CL, 0.32 and 0.72%), while the final estimate after adjusting for participation rates at 2nd and 3rd stages was 0.89% (95% CL, 0.6 and 1.1%). CONCLUSIONS: The results of the ECCIS study show that the prevalence of silent myocardial ischemia is definitely lower than that revealed by prior epidemiological studies in Norway and in USA. PMID- 7883128 TI - [Aortic valve replacement in old age. The results and follow-up echo-Doppler study of the prostheses]. AB - BACKGROUND: To analyze the results of aortic valve replacement in elderly patients and to evaluate the hemodynamic performance of valvular prostheses, we have retrospectively studied the patients 70 years of age or older, who consecutively underwent aortic valve replacement in our Center. METHODS: From January 1988 to December 1992, a series of 112 patients aged 70 to 88 years (mean 74.8 +/- 3.8 years) underwent aortic valve replacement; 49.1% of patients were male; aortic valvular lesion was: stenosis in 65.2%, insufficiency in 9.8% and mixed stenosis and insufficiency in 25.0%. In 73.2% isolated valve disease was present; in 25.0% coronary artery disease was associated. Preoperatively 58.9% were in New York Heart Association class III, and 29.5% were in class IV. Concomitant extracardiac diseases were present in 73.2%. The types of valve prostheses employed were: mechanical tilting disc (28 cases), mechanical bileaflet (40 cases), bioprosthesis (44 cases). A significantly favourable relationship between body surface area and size of prostheses was evident. RESULTS: Overall hospital mortality was 8.9% (5.4% for elective isolated aortic valve replacement) with significant difference (p = 0.006) related to criteria for surgical indication (elective 6.4%, urgent 10.0%, emergency 37.5%). Valvular lesion, age, sex, associated coronary artery bypass surgery, the values of peak and mean aortic valve gradient, the relative wall thickness and the presence of extracardiac disease have not been identified as risk factors for hospital mortality. The mean follow-up of the 102 discharged patients is 27.1 +/- 16.5 months (range 2 to 64 months). Eight late deaths (7.8%) occurred; the overall actuarial freedom from all deaths (excluding hospital mortality) was 95.6 +/- 2.2% at 1 year and 88.6 +/- 4.0% at 3 and 5 years. Five non fatal valve related complications occurred: hemorrhage in 4 cases (1.8% pt/yr) and hemolysis in 1 case (0.4% pt/yr). Ninety-seven percent of patients were found to be in NYHA functional class I or II. Comparative echocardiographic evaluation of the prostheses showed significant differences in mean gradient: regarding 21 mm size lower in bileaflet than in tilting disc and regarding 23 mm size lower in bileaflet than in tilting disc or bioprostheses. CONCLUSIONS: Aortic valve replacement has proved to be safe and effective in the elderly population and is considered the procedure of choice for aortic valve disease. Although we consider mandatory to choose the valve substitute matching different physiopathological and psychological attitudes of individual patient, mechanical prostheses and particularly bileaflet type for size < or = 21 mm should be preferred. PMID- 7883130 TI - [Cardiac retransplantation: is it justified in childhood?]. AB - A 7-year-old boy had undergone heart transplantation (HT) at 1 year of age. The immunosuppressive regimen consisted of cyclosporine and azathioprine (Cy+Aza). During the follow-up there were 7 episodes of moderate rejection: 4 of them occurred during the first 3 months. He had cytomegalovirus (CMV) seroconversion 4 years after HT. After 5 years since he underwent primary HT, cardiac catheterization and selective coronary angiography, performed on a yearly basis, showed triple vessel occlusive disease. The treadmill test was positive. During the following year, the patient's clinical condition deteriorated: in May '92 he underwent retransplantation. Cross-match was negative and there were no common HLA-DR antigens between the first and the second donor heart. Only 1 rejection episode occurred during the first 18 months of follow-up. Despite the shortage of donor hearts we feel that retransplantation is justified as an elective procedure in pediatric patients with cardiac allograft vasculopathy (CAV). PMID- 7883129 TI - [Arrhythmic symptoms and events in patients wearing an implantable automatic defibrillator]. AB - BACKGROUND: Although symptoms can be of some help in identifying the arrhythmia related to implantable cardioverter-defibrillator (ICD) discharge, symptomatic supraventricular arrhythmias and asymptomatic ventricular tachycardia have been reported. METHODS: In 18 survivors of cardiac arrest implanted with an ICD, the symptoms and intracardiac electrograms were systematically evaluated, in order to better define a relationship between some symptoms and supraventricular or ventricular tachyarrhythmias. RESULTS: A total number of 249 arrhythmic episodes were detected by the ICD during a mean follow-up of 378 +/- 107 days (range 137 to 642). Within this time, in 15 out of 18 patients (83%) at least one arrhythmic event alerting the device occurred, determining a therapeutic attempt in 13 patients. Only 49% of the episode stored by the ICD were symptomatic. Symptoms like palpitations, dizziness, "going under" lacked of predictability for ventricular tachycardia; in contrast, patients describing a "hot flush", alone or associated with palpitations, lightheadedness, dizziness most commonly recognized a ventricular tachyarrhythmias. This symptom had a good sensitivity (72%) and a high specificity (95%) in detecting a sustained ventricular tachycardia. CONCLUSIONS: Since in most cases symptoms are not a reliable criterion for validating ICD discharges stored electrograms during ICD activation need to be considered for analysis. However, the data of this study showed the importance of "hot flush" as a key symptom for recognizing the occurrence of a sustained ventricular tachyarrhythmia. PMID- 7883131 TI - [Obstruction of the superior vena cava following a corrective intervention for total anomalous pulmonary venous return treated by percutaneous angioplasty]. AB - We report a case of a patient operated on for total anomalous pulmonary venous drainage at the age of six months. Seven years later an angiographic examination showed a obstruction of superior vena cava at Juxta right atrial. The patient, asymptomatic until the age of fifteen, was then subjected to further hemodynamic and angiocardiographic examination due to the appearance of an incessant and therapy-resistant cough. After the diagnostic procedure was completed, percutaneous balloon angioplasty was performed on the obstruction, which marked the remission of the symptoms. PMID- 7883132 TI - [Prognostic stratification at discharge after acute myocardial infarct: the significance of the female sex. Participants in the GISSI-2 study. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico]. PMID- 7883134 TI - [Severe mitral insufficiency: the current surgical indications and new prospects]. PMID- 7883133 TI - [The evolution of hospital mortality due to acute myocardial infarct in the first 2 GISSI studies. Participants in the GISSI 1 and GISSI 2 studies. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico]. AB - During the short while of 5 years, between 1984 and 1985, two large clinical trials have been performed in Italy concerning fibrinolytic therapy in Acute Myocardial Infarction: GISSI 1 and GISSI 2. They made possible to evaluate the evolution of demographic and clinical features, the in-hospital mortality rate, and the causes of death of a huge number of patients admitted to CCU throughout the whole country. Out of 31,826 patients with acute myocardial infarction admitted to 176 CCU participating to the GISSI 1 16.9% were 75 years old and 24.7% were females; 21.8% and 26.4% were the percentages in the 38,086 patients admitted to the 223 CCU participating in the GISSI 2. Despite the higher prevalence of the two demographic characteristic with the worse prognosis, the in hospital mortality rates were respectively 12.2% in the GISSI 1 and 10.0% in the GISSI 2 studies, with a statistically significant decrease (RR 0.84; C.L. 0.80 0.88). The significant decrease in the in-hospital mortality concerns also the patients populations selected according to the same criteria of inclusion in the two trials (within 6 hours from the onset of symptoms and with only ST elevation at the ECG of admission) and to the treatment with fibrinolytic drug (SK or rtPA). As a matter of fact 468 patients died of the 4,696 (10.0%) treated with SK in the GISSI 1 against 1,092 patients of 12,381 (8.8%) enrolled in the GISSI 2 and treated with SK or rtPA (RR 0.87; L.C. 0.78-0.98). The reduction of in hospital mortality may be explained by some differences in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883135 TI - [Automatic defibrillator or anti-arrhythmia drugs for the therapy of patients who survived heart arrest or with syncopal ventricular arrhythmias? A critical analysis of the models relative to the studies in progress]. PMID- 7883136 TI - [Incessant ectopic atrial tachycardia during pregnancy: radiofrequency transcatheter ablation in the immediate postpartum with resolution of the relative picture of dilated cardiomyopathy]. PMID- 7883137 TI - [Does the absence of thrombi in the transesophageal echocardiogram justify cardioversion without anticoagulant prophylaxis in patients with atrial fibrillation?]. PMID- 7883138 TI - [The myocardial infarct patient arrives in the hospital 6 hours after the appearance of symptoms: is thrombolysis useful?]. PMID- 7883139 TI - [When is it useful after thrombolysis to subject the patient to predischarge coronary angiography?]. PMID- 7883140 TI - Seasonal changes in body mass, insulin, and glucocorticoids of free-living golden mantled ground squirrels. AB - The aim of the present study was to determine the relationship between seasonal variation in levels of insulin, cortisol, and corticosterone and body mass in a natural population of golden-mantled ground squirrels (Spermophilus saturatus) over the active season, from April to August. The body mass of females is at an active season minimum on emergence from hibernation, increases during pregnancy and lactation, and shows a further rise during fattening, reaching a peak in August. Males are heavier than females on emergence from hibernation, lose mass during the mating period, then gradually increase to a maximum in August. Plasma insulin titers generally reflected these patterns of change in body mass. Levels in males were almost double those of females on emergence, then decreased as body mass was lost during mating. Male values increased in July and peaked in August, coincident with the body mass maximum. Females, in contrast, showed very low insulin levels in April on emergence and increased levels during lactation, continuing high into the fattening period. Corticosterone levels were low in both sexes at the beginning of the season and rose throughout most of the active season; female levels exceeded those of males during the lactation phase. Cortisol titers gradually decreased over the first half of the active season in both sexes, but later increased to a seasonal maximum at the end of the season, coincident with the peak in body mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883141 TI - Adrenocorticotropic hormone in relation to interrenal function during stress in tilapia (Oreochromis mossambicus). AB - This study examines ACTH-like immunoreactivity in the pituitary pars distalis and pars intermedia of the freshwater teleost Oreochromis mossambicus (tilapia). Two products (tACTHA and tACTHB) were present in both lobes. These two products also accounted for the majority of the ACTH i.r. when in vitro pars distalis incubation medium was analyzed by HPLC. In a homologous bioassay the two tilapia ACTH-like molecules and human ACTH1-39 possessed similar corticotropic potency. The peptides were quantified using a newly validated radioimmunoassay, which was also used to measure ACTH in plasma of unstressed and stressed fish. Short-term (< 12 min) stress rapidly increased plasma cortisol, reaching levels of around 300 ng/ml in 5 min. Surprisingly, this initial elevation was not accompanied by a rise in plasma ACTH levels. A more prolonged (3 hr) confinement in pairs resulted in high plasma cortisol and ACTH levels in one fish of every pair. The second fish had control ACTH levels and only marginally elevated cortisol levels. Therefore, in this species social interactions seem to influence the reaction of the pituitary-interrenal axis to stress. The short-term cortisol response to disturbance could be abolished completely by pretreating fish in vivo with cortisol for 48 hr. This treatment did not alter circulating ACTH levels. It is concluded that tilapia did not rely on circulating ACTH for a rapid elevation of plasma cortisol levels. Both neuronal mechanisms and cortisol feedback may regulate the pituitary-interrenal axis at the level of the interrenal. PMID- 7883142 TI - A radioimmunoassay for recombinant-derived chicken prolactin suitable for the measurement of prolactin in other avian species. AB - A homologous radioimmunoassay for chicken prolactin is described. The assay is based on recombinant-derived chicken prolactin that has been used to raise an antibody and produce 125I-labeled tracer and assay standards. The radioimmunoassay measures a minimum of 0.03 +/- 0.01 ng of the recombinant prolactin with 50% displacement of binding by 0.6 +/- 0.1 ng. Chicken plasma and pituitary immunoreactivity dilute in parallel with the standard curve. The mean (+/- SE) concentrations of plasma prolactin were 12.1 +/- 1.5, 433.2 +/- 5.5, and 1609.8 +/- 18.5 ng/ml in out-of-lay, laying, and incubating bantam hens, respectively. The binding of recombinant prolactin was not displaced by extracts of neural lobe or plasma from a hypophysectomized hen. Plasma prolactin concentrations were increased after intravenous administration of chicken vasoactive intestinal polypeptide or quipazine, a 5-HT agonist. The assay measures immunoreactive prolactin in other birds. Plasma from quail, turkey, great tit, and wryneck displaced the 125I-labeled prolactin tracer parallel to the standard curve. Starling, ring dove, and penguin plasma displaced the binding in a nonparallel manner. PMID- 7883143 TI - Corticosterone-induced insulin resistance is not associated with alterations of insulin receptor number and kinase activity in chicken kidney. AB - Chicken renal insulin receptors have been recently characterized; their number and kinase activities vary in response to altered nutritional status. In the present study, the effect of chronic corticosterone treatment was examined in 5 week-old chickens. The development of an insulin resistance following corticosterone was suggested after 1 and 2 weeks of treatment by a significant increases in plasma insulin levels (1.63 +/- 0.13 vs 0.56 +/- 0.14 ng insulin/ml in controls) and in renal cytosolic phosphoenolpyruvate carboxykinase activity (17.2 +/- 0.8 vs 13.7 +/- 0.7 nm/mn/mg tissue in controls). No significant changes were present at the level of insulin receptor number and kinase activity. Therefore, in kidney and, as previously observed, in muscles, corticosterone can induce insulin resistance at postreceptor steps in the cascade of events leading to insulin action. PMID- 7883144 TI - Distribution and molecular forms of C-type natriuretic peptide in plasma and tissue of a dogfish, Triakis scyllia. AB - A radioimmunoassay (RIA) to measure C-type natriuretic peptide (CNP) of a dogfish, Triakis scyllia, was established, and plasma and tissue levels of CNP were measured. Molecular forms of CNP in plasma and tissues were also examined using a combination of the RIA and cation-exchange high-performance liquid chromatography (HPLC). The antibody used in the assay cross-reacted with all forms of Triakis CNP, as well as eel CNP, against which the antibody was raised. The antibody exhibited no cross-reaction with any atrial, brain (B-type), and ventricular natriuretic peptides examined and showed a weak cross-reaction with porcine CNP. The detection limit of this assay was 0.8 fmol/tube of Triakis CNP 22 which was used as standard. The CNP level in the Triakis plasma was 1.97 +/- 0.38 pmol/ml (n = 5) which far exceeded the physiological levels of any natriuretic peptides in other species. Among various tissues examined, the highest concentration of CNP was measured in the atrium, followed by the ventricle, brain, and pituitary. Low levels were detected in the kidney, liver, and digestive tracts. HPLC analyses revealed that the major form of CNP in the brain was CNP-22, while it was proCNP (CNP-115) in the heart. In contrast to other species from teleosts to mammals thus far examined, the majority of CNP in dogfish plasma was prohormone instead of processed, mature forms. PMID- 7883145 TI - Diffusion between the neurohypophysis and the adenohypophysis of lampreys, Petromyzon marinus. AB - Horseradish peroxidase (HRP), a protein that can be visualized by appropriate histochemical procedures, was injected into the third ventricle of the brain of adult lampreys, Petromyzon marinus. Within 5 to 15 min HRP had passed through the neurohypophysis, which forms the floor of the third ventricle. It appeared at this time to have diffused throughout the connective tissue separating the adenohypophysial follicles from the neurohypophysis and from each other. This observation would indicate that it is possible for neurosecretory peptides like gonadotropin-releasing hormone to diffuse from the brain (neurohypophysis) to the adenohypophysis and thus regulate its secretory activity in lampreys. PMID- 7883146 TI - Identification of the molecular forms of and steroid hormone response to gonadotropin-releasing hormone in the Australian lungfish, Neoceratodus forsteri. AB - Gonadotropin-releasing hormone (GnRH) peptides in the hypothalamus of the lungfish, Neoceratodus forsteri, were investigated by reverse-phase HPLC and RIA with region-specific antisera. Both chicken GnRH II and mammalian GnRH were identified, the latter being present in greater concentration. The steroidogenic response to a single intracardiac injection of synthetic mammalian GnRH was investigated in early and late spring (beginning and end of spawning season) and in early autumn. In early spring, both sexes responded with rapid and transient elevation of circulating steroid hormones. Testosterone in males showed the greatest response by elevating from 120 to 240 nmol/liter within 2 min of the injection and returning to approximately 100 nmol/liter within 15 min. Female lungfish showed a similar but slightly less dramatic response in circulating estradiol and testosterone. The responses of both males and females were reduced in late spring and abolished in early autumn, which is indicative of a period of seasonal refractoriness. PMID- 7883147 TI - Sex steroid binding proteins in the plasma of the green frog, Rana esculenta: changes during the reproductive cycle and dependence on pituitary gland and gonads. AB - Sex steroid binding proteins (SSBP) have been reported in the plasma of female and male Rana esculenta. In both sexes SSBP bind [3H]estradiol and [3H]testosterone with medium-high affinity and high specificity. Using ion exchange chromatography SSBP resolve into two peaks eluting at 0.27 M (peak I) and 0.36 M (peak II) NaCl. Both peaks bind [3H]estradiol and [3H]testosterone equally well. Isoelectrofocusing showed that peak I focused at pH 6.0 and 7.5, whereas peak II focused at pH 6.0. SSBP capacity for [3H]estradiol and [3H]testosterone changes throughout the reproductive cycle, showing low levels during the nonbreeding period and increasing levels during the breeding period. Hypophysectomy and/or gonadectomy result in small changes in SSBP capacity. Short term steroid hormone treatment of gonadectomized animals does not modify SSBP capacity. PMID- 7883148 TI - Spasmogenic actions of frog urotensin II on the bladder and ileum of the frog, Rana catesbeiana. AB - The effects of synthetic frog urotensin II on the motility of isolated smooth muscle strips of urinary bladder and ileum from the bullfrog Rana catesbeiana were investigated. The strips of bladder exhibited strong spontaneous contractions. Frog urotensin II produced a concentration-dependent increase in the frequency of contraction (EC50 = 8.1 x 10(-9) M) but had no significant effect on tension. Maximum stimulation (4 times the rate of spontaneous contractions) was produced by 10(-7) M peptide. The ileal smooth muscle strips exhibited only weak spontaneous contractions but frog urotensin II produced concentration-dependent increases in both the frequency (EC50 = 1.3 x 10(-9) M) and the strength (EC50 = 3.6 x 10(-9) M) of contraction. The peptide had no effect on the motility of strips of rat urinary bladder and ileum. In both the frog bladder and ileum preparations, the effect of urotensin II was not affected by preincubation of the strips with atropine, tetrodotoxin, and somatostatin-14 but indomethacin produced a significant (P < 0.05) decrease in the strength of the contractions of the bladder (to 21 +/- 6% of control values) and ileum (to 32 +/- 13%). Arachidonic acid produced an increase in the frequency of contraction of the bladder and an increase in both the frequency and the strength of contraction of the ileum. The data demonstrate that urotensin II exercises a spasmogenic effect on amphibian smooth muscle that is similar to that of the peptide on teleost tissues. An involvement of prostaglandin synthesis in the spasmogenic action of urotensin II on frog bladder and ileum is indicated. PMID- 7883149 TI - Rainbow trout ventricular natriuretic peptide: isolation, sequencing, and determination of biological activity. AB - Ventricular natriuretic peptide (VNP) is a new type of cardiac natriuretic peptide initially isolated from the eel ventricle. VNP has been isolated from cardiac ventricles of the rainbow trout, Oncorhynchus mykiss, and found to consist of 35 amino acid residues carrying a C-terminal tail sequence with 14 amino acid residues. Thus, the long C-terminal sequence characteristic of VNP was also conserved in the trout VNP. A VNP with 4 amino acid residues truncated from the C-terminus was also isolated from trout ventricles and sequenced. Sequence identity of trout VNP to eel VNP was 77%; while it was 56% to eel A-type natriuretic peptide (ANP). Trout VNP caused characteristic biphasic vasopressor/depressor effects in the trout similar to those produced by rat and eel ANP. Trout VNP and human ANP were almost equipotent in their vasopressor and depressor activity in trout. Unlike eel VNP, therefore, homologous VNP did not exhibit greater activity in the trout. In the rat, however, trout VNP was more potent than eel peptide and was almost equipotent to human ANP for both vasodepressor and natriuretic effects. The high potency of trout VNP appears to be due in part to its longer-lasting effect compared to human ANP. PMID- 7883150 TI - In vivo actions of a gonadotropin-releasing hormone (GnRH) antagonist on gonadotropin-II and growth hormone secretion in goldfish, Carassius auratus. AB - In our previous in vitro studies, [Ac-delta 3-Pro1, 4FD-Phe2, D-Trp3,6]-mGnRH (analog E) suppressed both gonadotropin-II (GTH-II) and growth hormone (GH) release stimulated by sGnRH and cGnRH-II. In the present study analog E significantly inhibited the increases in plasma GTH-II levels stimulated by sGnRH in sexually mature female and sexually recrudescent goldfish. Treatment of goldfish with alpha-methyl-p-tyrosin methyl ester (alpha-MPT) inhibits dopamine synthesis and abolishes the inhibitory actions of dopamine on GTH-II release, resulting in a potentiation of the GTH-II response to sGnRH. Following alpha-MPT pretreatment, analog E significantly reduced basal plasma GTH-II levels, and suppressed both sGnRH and cGnRH-II actions on GTH-II release. Analog E also inhibited the increase in plasma GTH-II levels in sexually mature male goldfish exposed to the female sexual pheromone, 17 alpha, 20 beta-dihydroxy-4-pregnen-3 one (17 alpha 20 beta-P), demonstrating that the increase in plasma GTH-II levels is due to release of endogenous GnRH. Analog E significantly inhibited the increases in plasma GH levels stimulated by treatment with sGnRH. Implantation of estradiol pellets increases basal plasma GH levels and increases the GH responsiveness to sGnRH in sexually recrudescent goldfish; analog E also suppressed the increase in plasma GH levels stimulated by injection of sGnRH in estradiol-treated fish. Analog E suppressed basal GTH-II and GH levels in fish that were unhandled prior to injection; however, analog E was not effective in reducing basal plasma GTH-II or GH levels in experiments in which the fish were blood sampled or subjected to some experimental manipulation prior to injection of analog E. Analog E also suppressed basal levels of GTH-II in alpha-MPT-treated fish, suggesting that stress inhibition of GTH-II release may be mediated by the dopaminergic system. In summary, the results demonstrate that (i) analog E can suppress the actions of exogenous sGnRH and cGnRH-II on GTH-II and GH release in vivo, (ii) the GnRH system mediates, at least in part, the plasma GTH-II response in sexually mature male goldfish following exposure to the female sexual pheromone 17 alpha 20 beta-P, and (iii) endogenous GnRH peptides are important in the regulation of basal plasma levels of GTH-II as well as GH, particularly in low stress conditions. PMID- 7883151 TI - A radioimmunoassay for the determination of arginine vasotocin (AVT): plasma and pituitary concentrations in fresh- and seawater fish. AB - A specific radioimmunoassay was developed and characterized for the measurement of arginine vasotocin (AVT) in teleost fish. Specificity of the antibody for AVT was demonstrated by parallelism of a series of AVT standards with serially diluted pituitary and plasma extracts. Crossreactivity of the antibody with the other teleost neurohypophysial peptide, isotocin, was less than 1% and the sensitivity of the assay was 0.24 fmol/assay tube. AVT was extracted from plasma by reverse-phase liquid chromatography [efficiency of 87.6 +/- 9.3% (n = 5)] and demonstrated as an effective procedure for plasma volumes ranging from 0.4 to 1.2 ml. Plasma AVT concentrations measured in a range of euryhaline and stenohaline teleost fish were between 10(-12) and 2 x 10(-11) M (1-20 pg/ml). There were no consistent differences between plasma AVT levels in euryhaline fish (flounder, trout, and eel) adapted to fresh water (FW) and sea water (SW). In flounder, pituitary AVT levels in FW- and SW-adapted fish were also similar. PMID- 7883152 TI - Induction of vitelline envelope proteins by estradiol-17 beta in 10 teleost species. AB - Induction of vitelline envelope proteins by estradiol-17 beta was investigated in 14 teleost species from five systematic groups to assess whether estradiol-17 beta controls the synthesis of vitelline envelope proteins in teleost fish. Vitelline envelope proteins were detected in plasma from fish treated with estradiol-17 beta using three different antisera directed against vitelline envelope proteins from three teleosts. Induction of vitelline envelope proteins was demonstrated in 10 species. In 6 of these species males were available and used to demonstrate that the synthesis of vitelline envelope proteins is not restricted to the ovaries. The immunoreactivity of the proteins varied considerably within and between species. It is suggested that the synthesis of vitelline envelope proteins is controlled by estradiol-17 beta in the majority of teleost species. PMID- 7883153 TI - [A comparative genetic analysis of interlinear differences in intensity of lipid peroxidation and life span in Drosophila melanogaster. Inbred lines and hybrids]. AB - The interrelationship between the level of peroxidation lipid and longevity was studied as based on highly inbred lines of Drosophila melanogaster, bred for adaptively important characters. The concepts of the free-radical theory proved valid for the lines and failed to be supported for the crosses. The dominant role of heterosis in the protecting against the "aging action" of free radicals is postulated. PMID- 7883154 TI - [The mechanism of the interchromsomal effect on crossing over in Drosophila melanogaster: delayed crossing over]. AB - Interchromosomal effect on crossing-over (IEC) in autosome 2 has been studied in 2/F(2L); F(2R) females heterozygous for free arms (acrocentrics) and in Is(Y;2)419/+ females with an insertion of Y-material into the region 34A. IEC was induced by In(1)dl-49 + BM1 inversion. Manifestations of IEC included increased recombinational length of chromosome 2 and decreased interference. IEC was not observed in Df(2L)TW161/+ females with 38A-40 deletion. The patterns of IEC in three types of gametes of the 2/F(2L); F(2R) female depended on the pairing relations of the affected chromosome (chromosome-responder). In the case of normal pairing between the metacentric autosome 2 (the metacentric) and the F(2R) acrocentric, the increment in 2R length was minimal (20%), and the increment in the proportion of multiple-exchange (high-rank) tetrads (E2 + E3), maximal (8 to 10%). In the case of disturbed pairing 2-F(2R) nondisjunction, 2R length was increased by 77%, paralleled by a minimal increase in the proportion of high-rank tetrads (4%). Similarly, in females with the insertion, a pronounced increase in 2L length (74%) was associated with a moderate level of high-rank tetrads. When pairing in the chromosome-responder was normal, the increment in crossing-over was maximal in the pericentromeric region. In the case of disturbed pairing, this maximum either shifted toward the middle of the arm 2-F(2R) nondisjunction, or occupied a distal position (in females with the insertion). It is concluded that IEC pattern depends on the order of pairing in the chromosome-responder. The mechanism of IEC appears to be related to pairing "defects" within the responder. It is tempting to speculate that the onset of crossing-over is a whole-cell event, which is regulated by the overall level of chromosome pairing within the meiotic cell. Chromosomal aberrations increase the time required for attaining this level, and the start of crossing-over is delayed. As a result, (1) exchanges are observed in the regions of late synapsis, which are usually not involved in crossing-over; (2) overabundance of recombination enzymes, caused by delayed start of crossing-over, creates the conditions for decreased interference in paired regions. PMID- 7883155 TI - [Prospects for obtaining a mapping panel for somatic cell marsupial-rodent hybrids for the short-tailed opossum Monodelphis domestica]. AB - A possibility of obtaining a panel of marsupial-rodent somatic cell hybrid clones has been explored, with a view to mapping the genome of the opossum (Monodelphis domestica). Fusion of opossum cells (splenocytes, bone marrow cells, and fibroblasts) with fibroblasts of Chinese hamster or vole (HGPRT- and TK- mutants, respectively) produced 146 hybrid clones. The majority of marsupial-mammalian somatic cell hybrids were characterized by pronounced fragmentation and segregation of marsupial chromosomes. To overcome this difficulty, a method for rapid screening was developed, which allowed the early selection of clones rich in chromosomal material of opossum. Based on the screening results, 25 clones of independent origin were selected. A detailed genetic analysis, which included chromosome G-banding and in situ hybridization of biotin-labeled opossum DNA on metaphase chromosomes, allowed further selection of seven hybrid clones containing one to six intact chromosomes of M. domestica. Opossum chromosomes were present in various combinations against the background of Chinese hamster or vole chromosomes. The clones will be included in the panel of opossum-rodent somatic cell hybrids, which is currently being created. PMID- 7883156 TI - [Restriction-deletion polymorphism of mitochondrial DNA region V in some populations of aboriginal residents of Siberia and the Far East]. AB - The distribution of a deletion and of an Ava II site in region V of mitochondrial DNA (mtDNA) was studied in five populations of native inhabitants of the Asian part of Russia, including Chukchi, Asian Eskimos, Evenks, Buryats, and Northern Sel'kups. A deletion with a frequency of 6.3% was found only in Buryats, In Chukchi and Eskimos the AvaII site was not found. A maximal frequency of 11.3% was observed in the Evenks. A comparison with published data was conducted; it revealed a gradient of decreasing frequency of the deletion from Southeast Asia to the North, with its complete absence in the circumpolar regions. In the territory of northeast Asia, all three mitotypes are found, formed by a combination of two polymorphic markers of mtDNA region V, which were found earlier in humans in the New World. The data obtained necessitates a more detailed analysis of the population polymorphism of mtDNA in this region of Asia. PMID- 7883157 TI - [Variability of biochemical gene markers in residents of the city of Tomsk]. AB - Variation of seven biochemical gene markers (Tf, Gc, Hp, ACP1, PGM1, PGD, and EsD) in the population of Tomsk was examined. The genetic structure of this population is compared to that of other urban populations from different regions of Russia. PMID- 7883158 TI - [Single-primer variant of PCR-amplifications of segments of the main noncoding region of human mitochondrial DNA]. AB - A method for amplifying segments of the main non-coding region of human mitochondrial DNA using a single-primer PCR is proposed. The method employs oligonucleotides that are homologous to this region of the human mitochondrial genome. Possible reaction mechanisms and the perspectives for using the method in evolutionary and population genetic studies are discussed. PMID- 7883159 TI - [Computer technology for genetic-geographical study of the gene pool. II. Statistical transformation of maps]. AB - Transformations of computer maps of geographical distribution of gene frequencies using basic mathematical statistical procedures are considered. These transformations are designated as statistical transformation of maps. Two transformation groups are considered: of one map separately and of a group of maps. Transformations possess a value beyond their use as intermediate stages of more complicated cartographical analysis: the resulting maps carry entirely new information on the geography of genes or a gene pool. This article considers three examples of obtaining new genetic profiles using statistical transformation algorithms. These profiles are of: heterozygosity (of HLA-A, B, C loci in northeastern Eurasia); (2) disease risk (Rh-incompatibility of mother and child with simultaneous registration of Rh and ABO blood groups in Eastern Europe); (3) genetic distances (from own mean ethnic values for Belarus' and from mean Russian values for the gene pool of Eastern Europe). PMID- 7883160 TI - [Differences in antimutagenic activity of vitamin preparations in human cells under the effect of various types of mutagens]. AB - The effect of ascorbic acid, retinol, and their mixture on the survival of human cells treated by mutagens was studied. The results provide evidence about the specific protective activity of each vitamin with respect to specific mutagenic effect. Information about specificity of "antimutagen-mutagen" effect accounting for mutagen cytotoxic properties can be readily obtained with the use of the method of vital cell staining with Tripane Blue. PMID- 7883161 TI - [Comparison of several Russian populations by vital statistics and frequency of genes, causing hereditary diseases]. AB - Distances computed from vital statistics using the Euclid formula and thus termed "vital" are proposed for use in population studies. An example of use of these statistics for comparison of four large geographically separated Russian populations is given. PMID- 7883162 TI - [Mapping of the gene for antidiuretic hormone in Rattus norvegicus]. AB - The gene for rat antidiuretic hormone was cytologically mapped using in situ hybridization. The gene was localized to chromosome 3, in region 3q41-q42. PMID- 7883163 TI - [Use of an information-search diagnostic system for recognizing acute hereditary metabolic diseases with early lethal outcomes]. AB - An information retrieval diagnostic system for hereditary metabolic diseases that are characterized by acute progression and early fatal outcome was developed. The system includes four databases: a list of nosological forms (n = 152), a list of clinical symptoms and characteristics (n = 1094), clinical portraits of every disease, and a list of biochemical characteristics (n = 1072). The system describes each disease as follows: clinical phenotype, etiology, genetics, pathogenesis, biochemical phenotype, paraclinical investigations, differential diagnosis, treatment, and prevention. PMID- 7883165 TI - G1 cyclin turnover and nutrient uptake are controlled by a common pathway in yeast. AB - Entry into a new cell cycle is triggered by environmental signals at a point called Start in G1 phase. A key regulator of this transition step in yeast is the CDC28 kinase together with its short-lived regulatory subunits called G1-cyclins or CLN proteins. To identify genes involved in G1-cyclin degradation, we employed a genetic screen by selecting for stable CLN1-beta-galactosidase fusion proteins. Surprisingly, one group of mutants was found to be allelic to GRR1, a gene previously described to be involved in glucose uptake, glucose repression, and divalent cation transport. In grr1 mutants, both CLN1 and CLN2 cyclins are significantly stabilized. A suppressor analysis indicated that G1-cyclin stabilization in grr1 was not a consequence of the nutrient uptake defect. This suggests that the GRR1 gene product is part of a common regulatory pathway linking two functions important for cell growth, nutrient uptake, and G1 cyclin controlled cell division. PMID- 7883164 TI - The Cpx two-component signal transduction pathway of Escherichia coli regulates transcription of the gene specifying the stress-inducible periplasmic protease, DegP. AB - DegP is a heat-shock inducible periplasmic protease in Escherichia coli. Unlike the cytoplasmic heat shock proteins, DegP is not transcriptionally regulated by the classical heat shock regulon coordinated by sigma 32. Rather, the degP gene is transcriptionally regulated by an alternate heat shock sigma factor, sigma E. Previous studies have demonstrated a signal transduction pathway that monitors the amount of outer-membrane proteins in the bacterial envelope and modulates degP levels in response to this extracytoplasmic parameter. To analyze the transcriptional regulation of degP, we examined mutations that altered transcription of a degP-lacZ operon fusion. Gain-of-function mutations in cpxA, which specifies a two-component sensor protein, stimulate transcription from degP. Defined null mutations in cpxA or the gene encoding its cognate response regulator, cpxR, decrease transcription from degP. These null mutations also prevent transcriptional induction of degP in response to overexpression of a gene specifying an envelope lipoprotein. Cpx-mediated transcription of degP is partially dependent on the activity of E sigma E, suggesting that the Cpx pathway functions in concert with E sigma E and perhaps other RNA polymerases to drive transcription of degP. PMID- 7883166 TI - Reciprocal interferences between nucleosomal organization and transcriptional activity of the yeast SNR6 gene. AB - Recent work has demonstrated a repressive effect of chromatin on the transcription of the yeast SNR6 gene in vitro. Here, we show the relations between chromatin structure and transcriptional activity of this gene in vivo. Analysis of the SNR6 locus by micrococcal nuclease digestion showed a protection of the TATA box, nuclease-sensitive sites around the A and B blocks, and arrays of positioned nucleosomes in the flanking regions. Analysis of a transcriptionally silent SNR6 mutant containing a 2-bp deletion in the B block showed a loss of TATA-protection and rearrangement or destabilization of nucleosomes in the flanking regions. Hence, SNR6 organizes the chromatin structure in the whole region in a manner dependent on its transcriptional state. Transcriptional analysis was performed by use of maxi-gene SNR6 constructs introduced into histone-mutated strains. Chromatin disruption induced by histone H4 depletion stimulated the transcription of promoter-deficient, but not of wild type SNR6 genes, revealing a competition between the formation of nucleosomes and the assembly of Pol III transcription complexes that was much in favor of transcription factors. On the other hand, amino-terminal mutations in histone H3 or H4 had no effect (H4) or only a moderate stimulatory effect (H3) on the transcription of promoter-deficient SNR6 genes. PMID- 7883167 TI - Identification and characterization of genes that are required for the accelerated degradation of mRNAs containing a premature translational termination codon. AB - In both prokaryotes and eukaryotes nonsense mutations in a gene can enhance the decay rate of the mRNA transcribed from the gene, a phenomenon described as nonsense-mediated mRNA decay. In yeast, the products of the UPF1 and UPF3 genes are required for this decay pathway, and in this report we focus on the identification and characterization of additional factors required for rapid decay of nonsense-containing mRNAs. We present evidence that the product of the UPF2 gene is a new factor involved in this decay pathway. Mutation of the UPF2 gene or deletion of it from the chromosome resulted in stabilization of nonsense containing mRNAs, whereas the decay of wild-type transcripts was not affected. The UPF2 gene was isolated, and its transcript was characterized. Our results demonstrate that the UPF2 gene encodes a putative 126.7-kD protein with an acidic region at its carboxyl terminus (-D-E)n found in many nucleolar and transcriptional activator proteins. The UPF2 transcript is 3600 nucleotides in length and contains an intron near its 5' end. The UPF2 gene is dispensable for vegetative growth, but upf2 delta strains were found to be more sensitive to the translational elongation inhibitor cycloheximide than UPF2+. A genetic analysis of other alleles proposed to be involved in nonsense-mediated mRNA decay revealed that the UPF2 gene is allelic to the previously identified sua1 allele, a suppressor of an out-of-frame ATG insertion shown previously to reduce translational initiation from the normal ATG of the CYC1 gene. In addition, we demonstrate that another suppressor of this cyc1 mutation, sua6, is allelic to upf3, a previously identified lesion involved in nonsense-mediated mRNA decay. PMID- 7883168 TI - Identification of a novel component of the nonsense-mediated mRNA decay pathway by use of an interacting protein screen. AB - Rapid turnover of nonsense-containing mRNAs in yeast in dependent on the product of the UPF1 gene (Upf1p). Mutations in UPF1 lead to the selective stabilization of mRNAs containing early nonsense mutations without affecting the decay rates of most other mRNAs. To identify other integral components of this decay pathway, we have employed a two-hybrid screen, seeking those cellular factors that specifically interact with Upf1p. Screening of yeast genomic libraries identified six genes encoding potential Upf1p-interacting proteins. These include four previously uncharacterized genes, NMD1-4 (nonsense-mediated mRNA decay), DBP2, a gene encoding a putative RNA helicase with homology to mammalian p68 RNA helicase, and SNP1, a gene encoding a U1 snRNP 70-kD protein homolog. In this paper we report the identification and characterization of NMD2, a yeast gene that encodes a specific Upf1p-interacting protein. Disruption of NMD2 yields a nonsense-mediated mRNA decay phenotype identical to that obtained in UPF1 deletion strains, indicating that the NMD2 gene product (Nmd2p) is a new factor in the nonsense-mediated mRNA decay pathway. Deletion analysis demonstrated that the acidic carboxyl terminus of Nmd2p constituted the Upf1p-interacting domain. High-level expression of a fragment of Nmd2p containing this domain had a dominant-negative effect on nonsense-mediated mRNA decay when the protein was localized the cytoplasm but not when it was localized to the nucleus, indicating that this decay pathway has a cytoplasmic component. The association of a dominant-negative phenotype with a gene fragment identified in a two-hybrid screen suggests a generalized approach to confirming the function of genes identified in such screens. PMID- 7883169 TI - RNA polymerase II subunit RPB9 is required for accurate start site selection. AB - The diverse functions of Saccharomyces cerevisiae RNA polymerase II are partitioned among its 12 subunits, designated RPB1-RPB12. Although multiple functions have been assigned to the three largest subunits, RPB1, RPB2, and RPB3, the functions of the remaining smaller subunits are unknown. We have determined the function of one of the smaller subunits, RPB9, by demonstrating that it is necessary for accurate start site selection. Transcription in the absence of RPB9 initiates farther upstream at new and previously minor start sites both at the CYC1 promoter in vitro and at the CYC1, ADH1, HIS4, H2B-1, and RPB6 promoters in vivo. Immunoprecipitation of RNA polymerase II from cells lacking the RPB9 gene revealed that all of the remaining 11 subunits are assembled into the enzyme, suggesting that the start site defect is attributable solely to the absence of RPB9. In support of this hypothesis, we have shown that addition of wild-type recombinant RPB9 completely corrects for the start site defect seen in vitro. A mutated recombinant RPB9 protein, with an alteration in a metal-binding domain required for high temperature growth and accurate start site selection in vivo, was at least 10-fold less effective at correcting the start site defect in vitro. RPB9 appears to play a unique role in transcription initiation, as the defects revealed in its absence are distinct from those seen with mutants in RNA polymerase subunit RPB1 and factor e (TFIIB), two other yeast proteins also involved in start site selection. PMID- 7883170 TI - flbD encodes a Myb-like DNA-binding protein that coordinates initiation of Aspergillus nidulans conidiophore development. AB - The timing of asexual fruiting body formation during Aspergillus nidulans colony development is precisely regulated so that conidiophores are typically produced 1 2 mm behind the growing edge of the colony. Mutations in any of four A. nidulans genes, flbB, flbC, flbD, or flbE, result in colonies that are delayed at least 24 hr in their ability to initiate conidiophore development resulting in fluffy colonies with conidiophores forming in the center, at least 12-15 mm behind the growing edge. The requirement for each of these four genes in determining the timing of developmental initiation precedes transcriptional activation of the primary developmental regulatory gene brlA, indicating a possible role for each gene in developmentally regulated activation of brlA expression. The wild-type flbD gene was isolated and shown to encode an approximately 1.6-kb mRNA that is present throughout the A. nidulans life cycle. The deduced FlbD protein sequence predicts a 314-amino-acid polypeptide with significant identity at its amino terminus to the DNA-binding domain of the Myb family of transcription factors indicating that FlbD probably functions as a sequence-specific transcriptional activator. Although conidiophore development does not normally occur in submerged culture, forced overexpression of flbD in submerged hyphae caused inappropriate activation of brlA expression and resulted in production of complex conidiophores that produced all of the distinct cell types observed in wild-type conidiophores including viable spores. This ability of flbD overexpression to activate conidiation requires brlA, flbB, and flbA (another early developmental regulator) but does not require flbC or flbE. We propose that FlbD functions during normal development by activating transcription of other genes required for development (such as brlA) and that FlbD activity is normally controlled post transcriptionally by an unknown mechanism. PMID- 7883171 TI - Cell-cell signaling pathway activating a developmental transcription factor in Bacillus subtilis. AB - Transcription in the mother cell at early stages of sporulation in Bacillus subtilis is controlled by sigma E, a sigma factor that is synthesized in the predivisional cell as an inactive larger precursor, pro-sigma E. Activation of sigma E depends on sigma F, the factor that governs transcription in the forespore. Genetic experiments have indicated that transduction of the activation signal from the forespore to the mother cell requires the products of some genes belonging to the sigma F-controlled regulon. We have identified and characterized a sigma F-dependent gene, csfX, encoding a protein necessary and sufficient for triggering processing of pro-sigma E. The CsfX protein contains a typical amino terminal signal sequence suggesting that, although synthesized in the forespore, it may act across the septum to activate the membrane-bound enzyme that is responsible for pro-sigma E processing in the mother cell. PMID- 7883172 TI - Photoaffinity cross-linking of TaqI restriction endonuclease using an aryl azide linked to the phosphate backbone. AB - In an effort to identify amino acid (aa) residues near the active site of TaqI restriction endonuclease (ENase), a sequence-specific photoaffinity reagent was designed. This reagent exploits the finding that modification of the Rp oxygen of the scissile phosphate does not interfere with substrate binding. The TpCGA phosphate was substituted with an Rp phosphorothioate group to direct the placement of the heterobifunctional reagent p-azidophenacyl bromide. TaqI bound the photoaffinity reagent specifically and formed a covalent adduct with the ENase in the presence of UV light. The modified aa was identified as Tyr161. This aa was changed to Phe by site-directed mutagenesis, and the resulting Y161F mutant was characterized. Removal of the Tyr161 hydroxyl group lowered both the kcat and the Km fivefold, indicating that, while this aa may be near the scissile phosphate, it is not critically required for catalysis. PMID- 7883173 TI - Nucleotide sequences transferred by gene conversion in the bacterium Acinetobacter calcoaceticus. AB - Exchange of nucleotide (nt) sequences between the catIJF and pcalJF regions of the Acinetobacter calcoaceticus chromosome appears to contribute to frequent repair of mutations, including removal of a Tn5 insertion from pcaJ. Repaired nt sequences are the products of nonreciprocal genetic exchange. The length of donor catIJF nt tracts recovered in repaired pcaIJF DNA ranged from less than 315 nt to more than 881 nt. This evidence does not distinguish gene conversion from natural transformation as a cause of repair, but natural transformation does not appear to contribute significantly, because it, unlike the repair process, is inactive in the presence of DNase. High-frequency recombination between catIJF and pcaIJF raises the question of why DNA between these chromosomal regions is stable. It is possible that some of the recombinational processes associated with gene conversion are unlike those underlying natural transformation. PMID- 7883174 TI - Analysis of the halobacterial plasmid pHK2 minimal replicon. AB - The pMDS series of cloning vectors developed for use in halophilic archaea have utilized a 10.5-kb plasmid, pHK2, from Haloferax sp. Aa2.2. The minimal replicon of pHK2 has now been determined (3359 bp) and completely sequenced. No significant sequence similarity was found between the pHK2 subfragment and plasmid pHV2 from the closely related H. volcanii. However, a long open reading frame (ORF), named rep, was identified which encodes a putative protein with approx. 30% sequence identity to ORFs within plasmids pGRB1, pHGN1 and pHSB1 from Halobacterium sp. All these putative Rep proteins contain sequence motifs conserved in bacterial plasmids and phage genomes known to replicate via a rolling-circle mechanism. PMID- 7883176 TI - Cloning and characterization of a novel polygalacturonase-encoding gene from Aspergillus parasiticus. AB - Pectinases produced by Aspergillus flavus and A. parasiticus are believed to play a significant role in the ability of these fungi to spread in cotton bolls and other crops. Utilizing a DNA probe, generated by PCR, of the Aspergillus niger pgaII gene, we have isolated a novel, constitutively expressed polygalacturonase (PG)-encoding gene (pecA) from an A. parasiticus cDNA library. DNA sequence analysis and the deduced amino acid (aa) sequence of pecA demonstrated significant identity at the nucleotide and aa levels with other PG of fungal origin. Northern blot analysis of RNA isolated from A. parasiticus grown on either glucose or pectin as the sole carbon source showed that pecA was expressed during growth in both media. PMID- 7883175 TI - Identification of four new prokaryotic bacterioferritins, from Helicobacter pylori, Anabaena variabilis, Bacillus subtilis and Treponema pallidum, by analysis of gene sequences. AB - The nucleotide (nt) sequence of the Helicobacter pylori (Hp) napA gene, encoding neutrophil-activating protein A (HPNAP) was determined. Alignment of this sequence with those of known bacterioferritins (Bfr) revealed sequence homology and conservation of a 7-amino-acid (aa) motif constituting the ferroxidase (Frx) center of Bfr in the HPNAP. The N-terminal aa sequence deduced from the iron regulated mrgC gene of Bacillus subtilis [Chen et al., J. Bacteriol. 175 (1993) 5428-5437] is highly similar to that of HPNAP and contains five Frx center aa residues. The deduced aa sequences for proteins of unknown function in Treponema pallidum [Walfield et al., Infect. Immun. 57 (1989) 633-635] and in the cyanobacterium Anabaena variabilis [Sato, GenBank accession No. JU0384 (1991)] identify these two proteins as Bfr. Although the DNA-binding protein from starved cells of Escherichia coli [Almiron et al., Genes Dev. 6 (1992) 2646-2654] is clearly a HPNAP/Bfr homologue, a significant part of its Frx center is missing. It is unlikely that the intracellular function of HPNAP is related to its ability to activate neutrophils. PMID- 7883177 TI - A phosphate-repressible, high-affinity phosphate permease is encoded by the pho 5+ gene of Neurospora crassa. AB - The pho-5+ gene of Neurospora crassa, which encodes a high-affinity phosphate permease, has been cloned and analyzed. The deduced ORF of 1707 nucleotides is interrupted by a single 63-nt intron and codes for a protein of 569 amino acids (aa). This aa sequence has 48% identity with the high-affinity phosphate transporter of Saccharomyces cerevisiae, PHO84. The pho-5 null mutants have no obvious phenotype. Strains which contain a null mutation in pho-4, which encodes an additional high-affinity phosphate permease [Bowman et al., J. Bacteriol. 153 (1983) 292-296], also have no obvious phenotype. However, strains containing mutations in both pho-5 and pho-4 are unable to grow under phosphate-restrictive conditions. PMID- 7883178 TI - Cloning and sequencing of the putative Azospirillum brasilense gene encoding GTP cyclohydrolase II. AB - Sequence analysis of a fragment of Azospirillum brasilense DNA revealed the presence of a ribA homologue, of which the 3' portion encodes a putative GTP cyclohydrolase II. The 5' portion (approx. half of the ORF) does not show homology to any other sequence from the databases. PMID- 7883179 TI - The carboxyphosphonoenolpyruvate synthase-encoding gene from the bialaphos producing organism Streptomyces hygroscopicus. AB - The nucleotide (nt) sequence of the Streptomyces hygroscopicus gene encoding carboxyphosphonoenolpyruvate (CPEP) synthase, that catalyzes a transesterification between phosphoenolpyruvate (PEP) and phosphonoformate (PF) in the bialaphos biosynthetic pathway, has been determined. The amino-acid sequence deduced from the nt sequence is similar to several eukaryotic 2-phospho D-glycerate hydrolases (EC 4.2.1.11). PMID- 7883180 TI - Sequence, expression and transcriptional analysis of the coronafacate ligase encoding gene required for coronatine biosynthesis by Pseudomonas syringae. AB - Pseudomonas syringae pv. glycinea PG4180 produces the chlorosis-inducing phytotoxin coronatine (COR), which consists of a polyketide component, coronafacic acid (CFA), ligated by an amide bond to coronamic acid (CMA), an ethylcyclopropyl amino-acid derived from isoleucine. We report the nucleotide sequence of a 2.37-kb region containing the coronafacate ligase-encoding gene (cfl) which is required for the amide linkage of CFA and CMA. The transcription start point for cfl was identified, and the Cfl protein was overproduced from the T7lac promoter in Escherichia coli. The deduced amino-acid sequence of Cfl showed homology to a variety of adenylate-forming enzymes which bind and hydrolyze ATP in order to activate their substrates for further ligation. PMID- 7883181 TI - Competence for genetic transformation in Streptococcus pneumoniae: organization of a regulatory locus with homology to two lactococcin A secretion genes. AB - Regulation of competence for genetic transformation in Streptococcus pneumoniae involves the comAB locus and a small extracellular protein, the competence factor (CF). The comA or comB mutations block both spontaneous competence induction and elaboration of CF, yet permit induction of competence by added CF and subsequent transformation at normal levels. Sequence and genetic studies showed that the com locus comprised the comA and comB genes, encoding 77- and 50-kDa proteins, respectively, and demonstrated that they were closely flanked by genes and DNA not required for competence regulation. In-frame deletion of comA demonstrated that the translation product of this gene is required for normal competence regulation; deletion-replacement mutations showed that no com gene lay in the 0.2 kb gap between comB and purC or within 2.5 kb upstream from comA. Strong sequence similarities (51-59% identities) showed that ComA and the proteins, PdcD and LcnC, which act in the secretion of pediocin A-1 and lactococcin A, respectively, form a subfamily within the large ABC-transporter protein family. ComB was found to be homologous to a single known protein, LcnD, required for secretion of the peptide antibiotic lactococcin A. Thus, the comAB locus displays homology to two lactococcin A secretion genes, but is devoid of additional linked com genes. The results suggest that the mechanism for CF production is similar to that for the small peptide bacteriocins, lactococcin A and pediocin A-1, but that its genetic organization is unusual in being split into at least two separate operons. PMID- 7883182 TI - Cloning of the genes encoding thymidine diphosphoglucose 4,6-dehydratase and thymidine diphospho-4-keto-6-deoxyglucose 3,5-epimerase from the erythromycin producing Saccharopolyspora erythraea. AB - Genes involved in deoxysugar metabolism, encoding thymidine diphospho (TDP) glucose 4,6-dehydratase (gdh) and a putative TDP-4-keto-6-deoxyglucose 3,5 epimerase (kde), were cloned from the erythromycin (Er)-producing Saccharopolyspora erythraea by means of an oligodeoxynucleotide corresponding to a segment of the purified Gdh protein. Determination of the nucleotide sequence established that kde lies 3' to gdh. The function of gdh was confirmed by an enzymatic assay following expression of the gene in Escherichia coli. Southern analysis indicated that Sa. erythraea contains only one copy of gdh and kde. It was not possible to establish whether these genes are required for Er biosynthesis, but they appear to be essential for cellular metabolism, since resolution of a partial diploid containing a wt and a disrupted copy of gdh always maintained the wt gene. These loci do not lie within or near the known boundaries of the cluster of Er-production and -resistance genes, nor do they appear to be flanked by other deoxysugar biosynthesis genes. PMID- 7883183 TI - Three genes hrdB, hrdD and hrdT of Streptomyces griseus IMRU 3570, encoding sigma factor-like proteins, are differentially expressed under specific nutritional conditions. AB - Three genes (hrd) homologous to the rpoD gene of Escherichia coli, that encode sigma factor-like proteins, have been cloned from DNA of the candicidin-producing strain Streptomyces griseus IMRU 3570. They are located in different regions of the chromosome. Sequence analysis showed that the first one is analogous to the hrdB gene of S. coelicolor. The second showed high similarity to the hrdD gene of S. coelicolor and S. aureofaciens and is linked, as in S. coelicolor, to a N acetyltransferase-encoding gene (nat) distantly related to the pat and bar genes that encode resistance to bialafos. The third showed no close homology with other known hrd genes from actinomycetes and has been named hrdT. Functional domains in the three S. griseus Hrd proteins are highly conserved in relation to those of the sigma 70 protein family. Northern analysis showed that hrdB is expressed as a 1.9-kb transcript during active growth in phosphate-rich medium, but it is less efficiently transcribed under sporulation conditions (phosphate-starved) or after a heat-shock treatment. Two other shorter transcripts of 1.2 and 0.7 kb were also detected with the same probe. The hrdD gene is transcribed as a single 1.1-kb transcript under sporulation conditions following nutritional shiftdown and, to a lower extent, during growth conditions in phosphate-rich medium. The hrdT gene is weakly transcribed (1.5-kb RNA) under all conditions tested. The hrd-encoded sigma factors probably recognize actinomycetes promoters (SEP type) with E. coli like consensus sequences. PMID- 7883184 TI - A group-I intron in the mitochondrial large-subunit ribosomal RNA-encoding gene of Dictyostelium discoideum: same site localization in alga and in vitro self splicing. AB - A 547-bp group-I intron belonging to subgroup IA1 was found near the 3' end of the large subunit ribosomal RNA-encoding gene (LSUrRNA) in the mitochondrial (mt) DNA of the cellular slime mold Dictyostelium discoideum. This intron was inserted in a highly conserved stretch within the sequence that encodes the peptidyl transferase center domain V in the corresponding region of the Escherichia coli LSUrRNA. Interestingly, the insertion site of the intron is the same as that of the So.LSU.2 intron of the green alga, Scenedesmus obliquus, mt DNA and the Pw.LSU.2 intron of the colorless alga, Prototheca wickerhamii, mt DNA. The intron could self-splice in vitro at a concentration higher than 20 mM MgCl2. Polymerase chain reaction analysis showed the possible existence of an intron similar to that of D. discoideum LSUrRNA in another cellular slime mold, Polysphondylium pallidum (CK-8), but not in D. mucoroides (Dm7 and Dm11). PMID- 7883185 TI - The pCLIP plasmids: versatile cloning vectors based on the bacteriophage lambda origin of replication. AB - A series of general-purpose plasmid vectors based on the phage lambda origin of replication (ori) has been constructed. Each vector consists of a backbone plasmid encoding chloramphenicol resistance (CmR) and containing a unique HaeII site into which the lacZ alpha-complementing multiple cloning site (MCS) region of an established vector was inserted. To increase the cloning potential of the inserted MCS, superfluous restriction sites in the backbone were removed by a variety of techniques. The vectors, designated pCLIP (for CmR lambda ori integration proficient) plasmids, are of medium copy number and are compatible with most other vectors in common use. A total of 17 unique restriction sites in pCLIP8, pCLIP9, pCLIP18, pCLIP19 and pCLIP23 are available for cloning. As well as possessing the usual properties of vectors, the pCLIP plasmids are able to integrate reversibly into lambda prophage by homologous recombination. Thus, cloned DNA can be maintained in single or multiple copy at will. By integrating recombinant plasmids into appropriate deletion prophages followed by induction, phage::plasmid hybrids are produced which can be manipulated as phage. These properties are demonstrated using a test recombinant plasmid, pCLIPLEU2. The pCLIP vectors are therefore useful for routine plasmid cloning, complementation analysis and applications where the ability to manipulate recombinants in plasmid, phage or prophage forms is advantageous. PMID- 7883186 TI - A versatile vector for controlled expression of genes in Escherichia coli and Salmonella typhimurium. AB - We have constructed two expression vectors based on the pJF118HE vector developed for Escherichia coli by Furste et al. [Gene 48 (1986) 119-131]. The tac promoter (ptac) was exchanged for the trc promoter (ptrc) and an NdeI site was created at the appropriate distance from the ribosome-binding site. The NdeI site permits cloning of a gene at its translation start point without altering the amino-acid sequence of the synthesized protein, while ptrc and the lacIQ gene confer inducible and controlable expression. We have tested these plasmids in E. coli and Salmonella typhimurium. PMID- 7883187 TI - Cloning and sequencing of a previously unidentified gene that is involved in the biosynthesis of heme in Escherichia coli. AB - We have isolated a number of porphyrin (Por)-synthesis mutants as light-resistant revertants of a light-sensitive strain delta visA (hemH) of Escherichia coli that accumulates protoPor IX in the cell. Among such mutants, we found a double mutant (H103) with mutations in hemA and in a new gene downstream of hemA. This new gene, designated hemK, was located at 27 min on the linkage map of the E. coli chromosome. By nucleotide (nt) sequencing, it was demonstrated that hemK forms part of the hemA-prfA-hemK operon and encodes 225 amino acids that show no significant homology to any protein in the standard databases. The mutant strain H103 formed small colonies and showed no catalase activity even in the presence of 5-aminolevulinic acid (ALA), indicating its inability to catalyze a step in the biosynthesis of heme from ALA. An extract of H103 cells has readily detectable ALA dehydratase and porphobilinogen deaminase activities. H103 cells carrying a plasmid that included only hemA as an insert accumulated protoPor and coproPor, but showed no sensitivity to light, a result that suggests that it may be deficient in protoporphyrinogen oxidase activity. PMID- 7883188 TI - Heterogeneity of the amino-acid sequences of Escherichia coli Shiga-like toxin type-I operons. AB - PCR was used to amplify approx. 1470-bp segments of DNA containing complete Shiga like toxin type I (sltI) operons from Escherichia coli strains belonging to serotypes O48:H21, O111:H- and OX3:H8. These fragments were cloned and DNA sequence analysis identified several variations, as compared with published sltI sequences. All three sltI genes analysed were more closely related to Shiga toxin encoding genes (sht) of Shigella dysenteriae type 1, than to previously published E. coli phage-encoded sltI genes. The greatest deviation in deduced amino acid (aa) sequence was observed in the SltI protein from the OX3:H8 strain, which differed from the phage 933J-encoded SltI by 9 aa in the A subunit and 3 aa in the B subunit. PMID- 7883189 TI - Genes encoding RubisCO in Pseudomonas hydrogenothermophila are followed by a novel cbbQ gene similar to nirQ of the denitrification gene cluster from Pseudomonas species. AB - The cbbL and cbbS genes, encoding ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO), were cloned and sequenced from a thermophilic hydrogen-oxidizing bacterium, Pseudomonas hydrogenothermophila strain TH-1. The cbbL gene encoded a 474-amino-acid (aa) protein (53,285 Da); cbbS encoded a 124-aa protein (14,656 Da). An ORF found downstream from the cbbLS genes encoded a 267-aa protein (29,565 Da) which had no similarity to cbbX located downstream from cbbLS from Alcaligenes eutrophus and Xanthobacter flavus. This gene, called cbbQ, was highly similar to the nirQ gene of the denitrification gene cluster from P. aeruginosa and P. stutzeri. PMID- 7883190 TI - Isolation and characterization of a Vibrio cholerae gene (tagA) that encodes a ToxR-regulated lipoprotein. AB - The Vibrio cholerae (Vc) gene (tagA) coding for the TagA lipoprotein has been isolated. Sequencing of tagA revealed the presence of an open reading frame (ORF) of 568 amino acids with a characteristic signal peptidase II cleavage site at the N terminus. Electrophoretic analysis of proteins synthesized by Escherichia coli (Ec) cells following T7 promoter/RNA polymerase-directed expression of tagA, revealed a closely migrating doublet of proteins corresponding to two species of TagA. Computer-generated alignment algorithms predict that a homology exists between Vc TagA and Ec K99 fimbriae biogenesis determinant FanD. PMID- 7883191 TI - A new mobilizable cosmid vector for use in Vibrio cholerae and other gram negative bacteria. AB - A new mobilizable cosmid vector, pCOS5, was engineered for use in Vibrio cholerae (Vc). Plasmid pCOS5 is small in size (7286 bp), contains the oriT from plasmid RK2, and has several unique restriction sites. The complete nucleotide sequence of pCOS5 was deduced from the DNA fragments used in its construction. Biparental matings using Escherichia coli (Ec) SM10 and triparental matings using Ec DH5 alpha[pRK2013] were used to measure the conjugation frequency of pCOS5 and pAJM1, a clone containing a 40-kb insert of chromosomal DNA from Vc ligated into pCOS5. Transfer of pCOS5 or pAJM1 to Vc occurred at a frequency of between 10(-2)-10(-3) transconjugants per recipient cell. The promiscuous nature of RP4/RK2 transfer functions makes pCOS5 a potentially useful vector for mobilizing large fragments of cloned DNA between different Gram- bacteria that support replication of ColE1 plasmids or as a mobilizable suicide vector in Gram- bacteria where replication of ColE1 plasmids is not supported. PMID- 7883192 TI - Sequence and arrangement of genes encoding sigma factors in Clostridium acetobutylicum ATCC 824. AB - The nucleotide sequence of a 2.7-kb region of Clostridium acetobutylicum ATCC 824 DNA containing three open reading frames was determined. They encoded homologs of three proteins of Bacillus subtilis, and the gene arrangement in both organisms was identical. The first gene, orfA, was 801-bp long; the 31-kDa (266 aa) product it encoded exhibited homology with the putative sigma E-processing enzyme. The second gene, sigE, was 708-bp long encoding a 27-kDa (235 aa) product; the third gene, sigG, was 774-bp long encoding a 30-kDa (257 aa) product. These two proteins showed high homology with sigma E and sigma G, two sporulation-specific sigma factors. PMID- 7883193 TI - Overproduction, purification and structural characterization of the functional N terminal DNA-binding domain of the fru repressor from Escherichia coli K-12. AB - A DNA fragment encoding the DNA-binding domain (amino acids 1-60) of the Escherichia coli fru transcriptional regulator was cloned into the pGEX-KT vector and expressed in frame with the fused gene encoding glutathione S-transferase. The fusion protein was purified to homogeneity by affinity chromatography on immobilized glutathione, and then cleaved with thrombin. After separation by a cation-exchange chromatography step, the DNA-binding domain exhibited proper folding, as shown by proton NMR analysis. Furthermore, it showed specific interaction with the operator region of the ace operon, as checked by gel retardation and DNA methylation-protection experiments. PMID- 7883194 TI - Identification of a chromosomally encoded ABC-transport system with which the staphylococcal erythromycin exporter MsrA may interact. AB - The energy-dependent efflux of erythromycin (Er) in staphylococci is due to the presence of msr A, which encodes an ATP-binding protein. MsrA is related to the multi-component ATP-binding cassette (ABC) transporters which characteristically also contain membrane-spanning domains. Since MsrA functions in a heterologous host in the absence of other plasmid-encoded products, the requirement for a transmembrane (TM) complex might be fulfilled by hijacking a chromosomally encoded protein. Two genes, stpA and smpA, were identified upstream from msrA on the original Staphylococcus epidermidis plasmid, encoding an ATP-binding protein and a hydrophobic TM protein, respectively. Sequences highly similar to stpA and smpA (stpB and smpB) were also found adjacent to a chromosomal copy of msrA in S. hominis. In Southern blots, internal fragments of stpA or smpA hybridized to the chromosome of the Ers S. aureus RN4220. Cloning and sequence analysis of the region identified revealed the presence of two genes, stpC and smpC, related to stpA and smpA. The deduced amino-acid sequences of the gene products showed that StpA and StpC were 85% identical, whereas SmpA and SmpC were 65% identical. A gene similar to msrA was not present in the S. aureus chromosome. There was no further sequence similarity outside these conserved regions. These results indicate that the chromosomes of S. hominis and S. aureus contain sequences encoding a potential TM protein with which MsrA might interact. PMID- 7883195 TI - Cloning, sequencing and expression of serine/threonine kinase-encoding genes from Streptomyces coelicolor A3(2). AB - A 6.3-kb DNA fragment encoding two eukaryotic-type serine/threonine protein kinases (Ser/Thr PK) was cloned from Streptomyces coelicolor A3(2) by using a PCR product obtained with primers based on highly conserved regions of eukaryotic Ser/Thr PK. The nucleotide (nt) sequence of the essential 4.4-kb fragment contained two possible ORFs. One ORF (PkaA) contained 543 amino acids (aa), while another (PkaB) consisted of 417 aa. The N-terminal half of both proteins showed significant similarity with the catalytic domain of eukaryotic Ser/Thr PK. On the other hand, the C-terminal region of PkaA, but not of PkaB, is rich in Pro and Gln residues, indicating that PkaA works as a PK as well as a transcription factor. The pkaB gene was overexpressed in Escherichia coli, and the gene product (PkaB) was found to be phosphorylated mainly at Thr. The pkaA gene was also overexpressed in E. coli, and the gene product (PkaA) was found to be phosphorylated mainly at Thr and slightly at Ser. In the case of PkaA, at least 100 aa residues from the C terminus were not essential for the PK activity. When the PCR product was used as a probe, it hybridized to DNA fragments from all the Streptomyces species tested, indicating that these types of Ser/Thr PK are distributed ubiquitously and play significant physiological roles in the various species of Streptomyces. PMID- 7883196 TI - 'How and why we age'. PMID- 7883197 TI - Multiple black lesions on the trunk. PMID- 7883198 TI - Hand and wrist disorders: how to manage pain and improve function. AB - Pain, swelling, or impaired function of the hand or wrist may be the result of one of several chronic or acute conditions, including tendinitis, arthritis, infection, or trauma. The first step in diagnosing a hand or wrist disorder is a detailed history. Include a review of the medical history, as many systemic disorders (eg, psoriasis, diabetes mellitus, rheumatoid arthritis, and scleroderma) may affect the hand and wrist. In the physical exam, assess motions of the cervical spine and those of all joints in the symptomatic extremity. A simple neurologic evaluation is required to assess function of the major nerves in the upper extremity. X-rays are indicated in any patient with hand or wrist pain. PMID- 7883199 TI - House calls: a practical guide to seeing the patient at home. AB - The physician and/or healthcare team is responsible for the planning, design, implementation, and authorization of home care services. Home visits are appropriate for elderly homebound patients and for those who are having problems at home, such as recent falls or suspected abuse. The home visit can provide valuable information that is not readily accessible in the office setting. At the home, the comprehensive geriatric assessment should include history and physical exam, plus a medication review, environmental evaluation, and assessment of functional status. Discussion with the family is also important, as caregiver burnout can adversely affect the well-being of the frail older patient living at home. Environmental modifications can improve home safety and reduce the risk for falls. PMID- 7883200 TI - Progressive dementia: strategies to manage new problem behaviors. AB - The primary care physician plays a key role in the diagnosis and treatment of progressive dementia and in coordinating supportive care with the patient's caregivers. When a patient exhibits a new symptom such as wandering or verbal abuse, your initial workup should eliminate acute medical illness, psychiatric disorders, and drug reactions that may present as behavioral symptoms. In the home, the main focus of care is to provide a safe and secure environment, using preventive measures to minimize the risk of injuries. When caregivers become exhausted from dealing with nocturnal wakenings, a short course of sleep medication for the dementia patient is often necessary. To improve communication, avoid stressful and confusing situations that compound the patient's difficulty in understanding messages or expressing thoughts. PMID- 7883201 TI - Slipping rib syndrome: don't be fooled. PMID- 7883202 TI - Pathogenic importance of muscular disorders in tension-type headache. PMID- 7883203 TI - MR-imaging of post-traumatic olivary hypertrophy. AB - We present clinical and magnetic resonance (MR) findings in 83 patients with inner cerebral trauma (ICT). In addition to the ICT-related lesions, uni- or bilateral enlargement and signal abnormalities of the inferior olivary nucleus were detected by MR in 9.6% of patients as a consequence of lesions within the dentato-rubro-olivary pathway. Clinically, segmental myoclonias were present in five patients. These observations suggest that MR imaging is highly sensitive in the detection of olivary hypertrophy and of causative traumatic lesions of the dentato-rubro-olivary pathway. PMID- 7883204 TI - Sleep in the last remission stages of vegetative state of traumatic nature. AB - Polygraphic studies were carried out on 20 patients (13 male, 7 female, average age 25.3 years) in the last remission stages of a traumatically caused vegetative state (apallic syndrome: stages V-VIII according to Gerstenbrand's classification). The presence of all the stages of NREM and REM sleep was observed in all patients, as was typical spindling activity. With respect to patients in the first remission stages of vegetative state, the total sleep time (TST) was seen to increase as a percentage of the total time in bed (95%) and with respect to TST, the periods of waking after a period of sleep diminished (wake after sleep onset: 9.73%). Stage I decreased (10.39%), while stages II-III IV increased (32.36%, 4.29% and 6.04% respectively). There was a clear increase in the REM percentage (37.19%); spindling rate and index both increased (4.9/min and 12.1 respectively). PMID- 7883205 TI - Sudomotor dysfunction in amyotrophic lateral sclerosis. AB - We performed a quantitative sudomotor function test on 11 patients with classic amyotrophic lateral sclerosis (ALS) and 11 age-matched control subjects. Thermal warming increased the sweat rate in the forearm of ALS patients and in the forearm and thigh of control subjects. The sweat rate in the thigh of ALS patients was lower than that of controls. Thyrotropin releasing hormone increased the sweat rate in the forearm and thigh and decreased oral temperature in both ALS and controls but the lower extremity response was reduced in ALS. Results of the sudomotor axon reflex test on the thigh indicate that in ALS, there is mild postganglionic sudomotor dysfunction. We conclude that patients with ALS have mild thermoregulatory sweat dysfunction due to postganglionic lesions in the lower extremities. PMID- 7883206 TI - Instability of R3 response of the blink reflex in patients with HAM/TSP. AB - HAM/TSP patients presenting interneuronal hyperexcitability of the brainstem displayed the R3 response with closed eyes but this was either diminished or disappeared contralaterally to the stimulation side when they were tested with their eyes open. Lack of regulation of the interneuronal network between R1 and R3 could be the most probable cause of these features. PMID- 7883207 TI - Electrocortical desynchronization after microinfusion of kainic acid into the locus coeruleus in rats. AB - Receptors for the endogenous excitatory amino acid, 1-glutamate, occur in the rat locus coeruleus (LC), an area of the brain involved in the control of sleep/arousal mechanisms and other behavioral functions. However, the functional role of this neurotransmitter system in the LC has yet to be clarified. Therefore, to address this question we have studied the gross behavioral changes and the effects on the electrocortical (ECoG) spectrum power in rats receiving focal injections into the LC of kainic acid, an agonist at the non-N-methyl-D aspartate (non-NMDA) glutamate receptor subtype. Unilateral injection of kainic acid (25, 50, 100 and 200 pmol) into the rat LC produced contralateral turning, circling and stereotypes; these effects were accompanied by dose-dependent ECoG desynchronization and by a significant decrease in total voltage power and in 6 9, 9-12 and 12-16 Hz bands of the ECoG spectrum. A pretreatment (15 min before) with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) (50 and 100 pmol), a competitive non-NMDA receptor antagonist, or with dizocilpine meleate (MK-801) (1 pmol) and 3 (2-carboxy-piperazine-4-yl)-1-propenyl-1-phosphonic acid) (CP-Pene) (10 pmol), two selective NMDA receptor antagonists, injected directly into the LC, abolished the behavioral and ECoG spectrum power effects typically elicited by kainic acid (50 pmol). Similar results were observed in rats pretreated with diazepam (0.5 mg/kg given i.p. 15 min before kainic acid).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883208 TI - Laparoscopic cholecystectomy. PMID- 7883209 TI - Hyposplenism in gastrointestinal disease. PMID- 7883211 TI - Functional defect of T cells in autoimmune gastritis. AB - The functional response and phenotypic characterisation of peripheral blood T cells were studied in 41 patients with autoimmune gastritis--nine patients with autoimmune gastritis alone, 11 with untreated pernicious anaemia, and 21 with resolved pernicious anaemia who were taking vitamin B-12. Phenotypic analysis showed no changes in the CD4/CD8 ratio in any group of patients. CD3+ cells were significantly decreased and CD16+ cells were significantly increased in patients with autoimmune gastritis alone. Phytohaemagglutinin induced T cell proliferation, with or without interleukin 2, was reduced in the three groups. T cell proliferation induced by phorbol myristate acetate was normal. Interleukin 2 production of phytohaemagglutinin-stimulated lymphocytes was normal in the three groups. Five patients with pernicious anaemia treated with vitamin B-12 were followed and persistent hypoproliferation of T cells in response to phytohaemagglutinin was observed. The follow up study of the phenotype of these patients showed a significant increase of the CD2+ CD3- lymphocyte population after six months' treatment. In conclusion, the three groups of autoimmune gastritis patients studied have a functional defect in T cells that is independent of B-12 treatment and of the presence of pernicious anaemia. PMID- 7883210 TI - Artificial livers--what's keeping them? PMID- 7883212 TI - Satiety effects of a physiological dose of cholecystokinin in humans. AB - Cholecystokinin 33 (CCK) was infused intravenously to eight healthy obese women and 10 healthy lean women of the same age, in doses that elicited plasma cholecystokinin concentrations in the physiological range. The effect of these infusions after a standardised banana 'shake' (preload) on food intake and satiety signals was compared with the effect of saline infusions in the same subjects. For the whole group food intake (mean (SEM)) (282 (29 g)) was significantly less during CCK than during saline (346 (31) g, p < 0.05). Hunger feelings tended to be less during CCK infusions. Examination of the separate subgroups showed no differences between lean and obese subjects in the satiety effects of CCK. In conclusion, under the conditions of this study, CCK significantly decreases food intake in humans, and this effect is similar for lean and obese subjects. PMID- 7883213 TI - Reasons for variations in the use of open access gastroscopy by general practitioners. AB - This study aimed to investigate the wide variation between general practitioners (GPs) in their use of open access gastroscopy by assessing (i) their partnership share, workload, and the aggregated practice request rate; (ii) correlations with their professional and practice characteristics; and (iii) a comparison with referral rates to medicine, surgery, and all specialties. All 145 GPs and their practice managers were sent a questionnaire and hospital held data on all requests for open access gastroscopy over one year were reviewed. During the year, the 145 GPs made 1210 requests for open access gastroscopy, varying from one to 44 per GP. There were 987,880 practice consultations altogether, an average of 22,451 per practice or 7127 per whole time practitioner. Requests for open access gastroscopy formed 2.4% of all referrals, an average of one per 1000 consultations, or eight per GP. Of a total of 49,123 referrals to all specialties (371 per GP) 4218 (8.5%) were to medicine, and 6444 to surgery (13.1%). The following factors did not correlate with requests: vocational training, a concurrent hospital post, length of service, or receipt of the deprivation allowance by the practice. When the open access gastroscopy referral rate was aggregated for each practice the variation between practices was narrowed to essentially twofold. Requests for open access gastroscopy form a small proportion of all referrals (2.4%). Aggregated practice request rates are relatively uniform compared with the wide variation between individual GPs, suggesting a disproportionate gastroenterology workload between partners. The open access gastroscopy service does not seem to be subject to misuse from most GPs if a variation in practice usage is used as a measure. PMID- 7883214 TI - Relation between gastric emptying rate and energy intake in children compared with adults. AB - Measurement of gastric emptying rate of solids in children is difficult because the available methods are either invasive or induce a substantial radiation burden. In this study the newly developed 13C octanoic acid breath test was used to examine the gastric emptying rate of solids and milk in healthy children and to compare gastric emptying in children and adults. Fifteen healthy children and three groups of nine healthy adults were studied, using three different test meals labelled with 50 mg of 13C octanoic acid: a low caloric pancake (150 kcal), a high caloric pancake (250 kcal), and 210 ml of milk (134 kcal). Breath samples were taken before and at regular intervals after ingestion of the test meal, and analysed by isotope ratio mass spectrometry. The gastric emptying parameters were derived from the 13CO2 excretion curves by non-linear regression analysis. No significant difference was found between children and adults in the emptying rate of the low caloric solid test meal. In children as well as in adults, increasing the energy content of the solid meal resulted in a significantly slower emptying rate. The milk test meal, however, was emptied at a faster rate in adults and at slower rate in children compared with the low caloric solid test meal. Moreover, the emptying rate of milk in children was significantly slower than in adults. In conclusion, a similar gastric emptying rate of solids but a slower emptying of full cream milk was shown in children of school age compared with adults, using the non-radioactive 13C octanoic acid breath test. PMID- 7883215 TI - Importance of reflux symptoms in functional dyspepsia. AB - The relation between symptom severity in gastro-oesophageal reflux disease (GORD) and quantitated oesophageal acid reflux is variable. Furthermore, when oesophageal acid exposure lies within the conventional normal range, the cause of the symptoms is unknown. This prospective study evaluated 24 hour ambulatory oesophageal pH profiles in relation to objective symptom scores in 100 dyspeptic patients who were free from ulcer and gall stones. Twenty patients had raised oesophageal acid exposure and reflux symptoms consistent with GORD, and 80 had oesophageal pH profiles within the conventional normal range. Forty four of the 80 had severe or moderate reflux symptoms and were classified as having reflux like functional dyspepsia (RFD); 36 had minimal or absent reflux symptoms, and were categorised as having non-reflux dyspepsia (NFD). While oesophageal pH profiles lay within the conventional normal range in both functional dyspepsia subgroups, patients with RFD had consistently greater acid exposure values as follows: mean (SEM) total oesophageal acid exposure time, RFD 16.2 (2.56) min v NFD 9.05 (2.0) min (p < 0.03); percentage of time with pH < 4, RFD 1.4 (0.2) v NFD 0.8 (0.2) (p < 0.03); DeMeester scores, RFD 12.8 (0.5) v NFD 11.4 (0.4) (p < 0.03). The RFD group had a pain/reflux event correlation of 23.8 (5.3)% v 8.1 (3.7)% for the NFD group (p < 0.01). This study shows that patients with RFD have oesophageal acid exposure that lies below the diagnostic threshold for GORD, but exceeds that of patients with NFD. The high pain/reflux event correlation in RFD, suggests that subthreshold oesophageal acid exposure may be associated with troublesome reflux symptoms. PMID- 7883216 TI - Effect of Helicobacter pylori eradication on gastric metaplasia of the duodenum. AB - Helicobacter pylori associated duodenal ulcers occur in patches of gastric metaplasia. The pathogenesis of gastric metaplasia is unclear, but it has been produced in experimental animals by acute injury and has been shown to be present to a greater extent of H pylori positive subjects. This study aimed to discover if gastric metaplasia regressed with eradication of H pylori or healing of duodenal ulcers, or both. Thirty two duodenal ulcer patients with H pylori infection confirmed by biopsy urease test and by antral histological examination were studied. Patients were treated with triple therapy (deNol 240 mg twice daily, amoxycillin 500 mg three times daily, and metronidazole 400 mg three times daily) for two weeks after the first endoscopy and were subsequently re endoscoped. Three duodenal bulb biopsy specimens were obtained per patient at each endoscopy. Biopsy sections were stained with haematoxylin and eosin to determine the severity of duodenitis, and with diastase periodic acid Schiff/alcian blue to assess the extent of gastric metaplasia. Slides were assessed by two histopathologists unaware of treatment status. H pylori was eradicated in 63% of subjects and all ulcers were healed at follow up. The median extent of gastric metaplasia at the start of treatment and 6-18 months (median 10) after treatment was compared in the two groups. Gastric metaplasia declined in eradicators from 16% to 8% (p < 0.05) while in non-eradicators there was no significant change (25% initially and at follow up). A positive relation between extent of gastric metaplasia and duodenal inflammation score was present before treatment (r(s) = 0.74, p < 0.001) and was unchanged after treatment in the non eradicator group (r(s) = 0.89, p < 0.001). In the eradicator group, however, the inflammation score had significantly declined (p < 0.02) and the close relation with gastric metaplasia was no longer present. These results suggest that H pylori itself is at least in part responsible for producing gastric metaplasia of the duodenum. PMID- 7883217 TI - Helicobacter pylori associated with a high prevalence of duodenal ulcer disease and a low prevalence of gastric cancer in a developing nation. AB - This study examines the relationship between Helicobacter pylori infection and peptic ulcer disease and gastric cancer--in particular, the presence or absence of bacteria, the grading of gastritis, and the degree of inflammation in the antral and oxyntic mucosae. The grading of gastritis and the detection of H pylori were determined by histology using the Sydney system. Of the 1006 patients examined, 34.5% had duodenal ulcer disease, 3.5% gastric ulcer disease, and 2% with coexistent ulceration. Most patients (50.2%) were classified as having non ulcer dyspepsia. Altogether 2.4% of patients had gastric cancer and two further patients had carcinoma in the gastric stump. Of the ulcer disease patients, 87.2% had histological evidence of H pylori infection. After patients who had taken antibiotics or bismuth compounds in the preceding four weeks were excluded, 98.9% of the duodenal ulcer disease, 100% of the gastric ulcer disease, and 100% of the coexistent ulcer disease patients had evidence of H pylori infection. In patients with gastric cancer who had not taken antimicrobial agents in the four weeks before endoscopy, 83.3% had evidence of H pylori infection. Thus, there was a high rate of duodenal ulcer disease and a low rate of gastric ulcer disease in southern China, an area of low gastric cancer mortality. There was a specific topographical relationship between H pylori, the histological response, and gastroduodenal disease. Our data suggest that the status of a nation as either 'developed' or 'developing' can not be used to predict the upper gastrointestinal disease profile of its population. PMID- 7883218 TI - Gastrin and the growth of the gastrointestinal tract. AB - While the proliferative effects of gastrin in the gastric fundus are well established, there is a considerable degree of confusion regarding the role of gastrin on the growth of the small intestine and colon. The hypothesis that gastrin is trophic throughout the gut was tested by giving three doses of pentagastrin and one of gastrin 17 to rats maintained by total parenteral nutrition (TPN). The rats were fed intravenously for one week, with the various peptides added to the TPN diet. The number of vincristine arrested metaphases per gland or crypt was then scored to determine the proliferative state. Both gastrin 17 and pentagastrin were found to be trophic in the gastric fundus, but not to the gastric antrum. A proliferative response was also seen in the duodenum, but with little evidence of a dose response element. No effect on small bowel weight was seen, and no proliferative effect was noted in the mid small bowel, thus the duodenal effect could be attributed to a local action of increased acid output on the duodenum, not a general role throughout the small intestine. No proliferative effects of pentagastrin or gastrin were seen in the colon. It is therefore concluded that the trophic role of gastrin is restricted to the gastric fundus and the proximal duodenum. PMID- 7883219 TI - Rat intestinal mucosal responses to a microbial flora and different diets. AB - The effects of diet on the histochemical composition of intestinal mucosubstances and the morphology of the villi and crypts were investigated by comparing the data of germ free and conventionally maintained rats fed either a purified diet or a commercial diet. The influence of intestinal microflora was evaluated by comparing the germ free rats and those harbouring either a conventional rat flora or a human microbial flora. In both germ free rats and those maintained conventionally, feeding a purified diet resulted in shallower crypts in the small intestine but deeper crypts in the large intestine compared with their counterparts fed on the commercial diet. The preliminary data obtained with association of human flora showed a reduction of the villus height and crypt depth in the small intestine and, to some extent, the amount of neutral mucins in the goblet cells of both small and large intestine and an increase in the amount of sulphated mucins in the large intestine. In rats given the commercial diet the periodic acid Schiff staining for neutral mucins was more intense in the upper crypts of the small intestine than in the lower crypts, and to a lesser extent in the upper crypts of the large intestine. These results provide evidence that the dietary composition, microbial flora, as well as the interactions between the dietary constituents and microbial flora change the mucosal architecture and the mucus composition and therefore alter the functional characteristics of the intestinal tract. PMID- 7883220 TI - Chloride dependent amino acid transport in the human small intestine. AB - Carriers of beta amino acids and imino acids in the small intestine of rabbits and guinea pigs are chloride dependent, and a cotransport of chloride, sodium, and 2-methyl-aminoisobutyric acid has been shown. This study examines the chloride dependence of amino acid transport in the human small intestine. The steady state tissue uptake of amino acids, given as the ratio between substrate concentration in intracellular and extracellular water after 35 minutes incubation at 37 degrees C, was determined in mucosal biopsy specimens from the duodenum of patients undergoing diagnostic upper endoscopy and compared using one way analysis of variance. Uptake of leucine and alpha-methyl-D-glucoside in the duodenum and the distal ileum did not differ. The accumulation of all substrates was sodium dependent. In the absence of mucosal chloride the uptake of taurine, glycine, and 2-methyl-aminoisobutyric acid was significantly reduced while that of leucine and alpha-methyl-D-glucoside was unaffected and the reduction of beta alanine uptake not statistically significant. Uptake of 2-methyl-aminoisobutyric acid and proline showed mutual inhibition. Leucine did not reduce uptake of the beta amino acids. In conclusion, chloride dependent transport processes for 2 methyl-amino-isobutyric acid, taurine, and glycine are present in the human small intestine. PMID- 7883221 TI - Characterisation of the influence of anti-gastrin, anti-epidermal growth factor, anti-oestradiol, and anti-luteinising hormone releasing hormone antibodies on the proliferation of 27 cell lines from the gastrointestinal tract. AB - Numerous data from published reports prove that the proliferation of gastrointestinal tumour cell lines are under the control of many hormones or growth factors, or both. Most of these publications report the influence on a very small number of cell lines of one or two such factors only. This work deals with the in vitro characterisation of the influence of the anti-gastrin, the anti epidermal growth factor (EGF), the anti-oestradiol (E2), and the anti-luteinising hormone releasing hormone (LHRH) antibodies on the proliferation of a large series of gastrointestinal cell lines. Cell proliferation was assessed by means of the colorimetric MTT assay on a series of 27 gastrointestinal cell lines obtained from the American Type Culture Collection (ATCC). Of the 27 cell lines, the anti-gastrin, the anti-EGF, the anti-E2, and the anti-LHRH neutralising antibodies considerably influenced the proliferation of 13, 25, 12, and 16. No gastrointestinal cell line was unresponsive to the four antibodies simultaneously. The anti-gastrin and anti-EGF antibody induced effects on the 27 gastrointestinal cell line proliferation were significantly correlated, as was also the case for the anti-E2 and anti-LHRH antibody induced effects. Of the anti gastrin, the anti-EGF, the anti-E2, and the anti-LHRH antibodies, it was the anti EGF one that had the greatest influence, both quantitatively and qualitatively, on gastrointestinal cell proliferation. The correlation of the effects of definite anti-hormone antibodies is suggestive of a common mechanism of action for the corresponding hormones and casts some doubt on the efficiency of anti hormone monotherapy. PMID- 7883222 TI - Sequential changes in small intestinal structure and function during rotavirus infection in neonatal rats. AB - Rotavirus infection is the most common cause of acute diarrhoea in children worldwide. The structural and functional consequences of mammalian rotavirus infection in the small intestine have been incompletely studied and the mechanism of enterocyte damage poorly defined. This study used a neonatal rat model of group B rotavirus infection to study the natural history, clinical features, and the structural and functional consequences of infection in the small intestine. Group B rotavirus infection in eight day old neonatal rats produced diarrhoea by 24-36 hours, which was accompanied by weight loss during the early stages of infection. By seven days the diarrhoea had ceased and body weight was similar to noninfected controls. Rotavirus could be recovered in faeces from 24-72 hours. Light microscopy and morphometry confirmed reduction in villous height in both jejunum and ileum, with a reduction in total mucosal thickness indicating true flat mucosa. Increase in crypt depth followed villous shortening and continued as villous height progressively increased between 96-168 hours. Steady state perfusion of the entire small intestine with a plasma electrolyte solution confirmed the presence of a net secretory state for water between 12-48 hours, with a parallel reduction in sodium absorption. Group B rotavirus infection produces a self limiting acute diarrhoeal illness in neonatal rats similar to human rotavirus infection. Infection causes a reversible flat mucosa resulting from enterocyte loss associated with a net secretory state for water and impaired sodium absorption as a functional correlate. These findings may have relevance for the pathogenesis of human rotavirus infection. PMID- 7883223 TI - Seroconversion of reticulin autoantibodies predicts coeliac disease in insulin dependent diabetes mellitus. AB - Serum IgA class reticulin autoantibody test was performed prospectively once a year on 238 children and adolescents with insulin dependent diabetes mellitus (IDDM). At the initial testing, within one year after onset of IDDM, five were positive and 233 were negative. During follow up a further 11 of the initially antibody negative children became positive (6.7%). Jejunal biopsy was performed at the appearance of the autoantibodies and silent coeliac disease was shown in nine (3.8%). One of these children showed on initial biopsy after the onset of IDDM to have normal jejunal mucosal architecture deteriorating later to a flat lesion. Jejunal immunohistochemical studies of another of the patients positive for reticulin autoantibodies but normal on routine biopsy showed an increased density of intraepithelially located gamma/delta T cells and aberrant HLA-DR expression in the crypts pointing to ongoing mucosal inflammation and potential coeliac disease. This study shows that in IDDM patients, reticulin autoantibody negative subjects become antibody positive, which may be followed by coeliac disease. Repeated serological screening and rebiopsy should be considered to detect late developing clinically silent coeliac disease among patients with IDDM. PMID- 7883224 TI - Quantification of inflammatory bowel disease activity using technetium-99m HMPAO labelled leucocyte single photon emission computerised tomography (SPECT). AB - Technetium-99m HMPAO labelled white cell bowel uptake was quantified in 23 patients with suspected colitis by means of the novel technique of single photon emission computerised tomography (SPECT) using a standard gamma-camera. Uptake in colon segments was quantified on transaxial images and expressed as a fraction of marrow uptake (SPECT score). Segmental histological disease activity was assessed at colonoscopy (20) or at surgery (3). Segmental histology score correlated with SPECT score r = 0.79 (p < 0.001). Overall SPECT score for all affected segments correlated with Crohn's disease activity index (CDAI) r = 0.66, p = 0.001 and with laboratory activity indices; erythrocyte sedimentation rate r = 0.44, p = 0.03, C reactive protein r = 0.38, p = 0.05, and albumin r = -0.46, p = 0.03. Small bowel SPECT score in 13 patients correlated with CDAI r = 0.65, p < 0.01 but not with erythrocyte sedimentation rate or C reactive protein. Five patients with positive small bowel white cell uptake had normal C reactive protein and erythrocyte sedimentation rate. Overall SPECT score for disease at all sites correlated with both CDAI and with laboratory indices of inflammation. 99mTc HMPAO SPECT provides non-invasive and accurate quantification of inflammatory bowel disease activity in both large and small bowel and may be useful in the objective evaluation of treatment for inflammatory bowel disease. PMID- 7883225 TI - Caffeine phenotyping of cytochrome P4501A2, N-acetyltransferase, and xanthine oxidase in patients with familial adenomatous polyposis. AB - Patients with familial adenomatous polyposis (FAP) and age and sex matched controls were tested for cytochrome P4501A2 (CYP1A2), N-acetyltransferase, and xanthine oxidase activities using caffeine urinary metabolites as a discriminator. FAP patients showed significant underactivity of N acetyltransferase (which inactivates some carcinogens) and significant overactivity of CYP1A2 (which activates some carcinogens). Xanthine oxidase activity, which can generate free radicals and cause cellular damage, was significantly increased in the FAP patients. All but one of the FAP patients had undergone colectomy. A separate group of six patients was therefore assessed before and at an average time of eight weeks after colectomy. No effect on enzyme activity was seen. The differences in enzyme activities detected in this study could produce an excess of active carcinogenic metabolites in the bile of FAP patients and contribute to the high risk for intestinal cancer in FAP. PMID- 7883226 TI - 1,25-Dihydroxyvitamin D3 and retinoid X receptor expression in human colorectal neoplasms. AB - Epidemiological studies suggest that 1,25-dihydroxyvitamin D3 (D3) protects against colorectal carcinogenesis. Animal and in vitro studies show an antiproliferative effect of D3 in a variety of tumours including those of large bowel origin. D3 actions are mediated by D3 receptors (VDR) alone or by VDR in conjunction with retinoid X receptors (RXRs) in all D3 responsive tissues. The expression of mRNAs encoding VDR and RXRs in normal and malignant human colorectum was determined. Full length VDR (4.6 kB), RXR alpha (5.5 kB), and RXR gamma (3.5 and 7 kB) mRNAs were expressed in all tissues, but RXR beta mRNA was not expressed in any. VDR expression was reduced in 12 carcinomas relative to paired normal mucosa, and RXR alpha expression was reduced in nine. There was no correlation between VDR or RXR alpha expression and the site, grade of differentiation, or Dukes's staging of the tumour. The finding of persistent VDR and RXR coexpression in all colorectal tumours provides a rational basis for exploring a role for D3 in the treatment of colorectal malignancy. PMID- 7883227 TI - Characterisation of CYP3A gene subfamily expression in human gastrointestinal tissues. AB - The human CYP3A subfamily is of interest due to its multiplicity, activity toward known carcinogens, and extrahepatic expression. In situ hybridisation analysis of formalin fixed, routinely processed biopsy specimens was used to localise CYP3A mRNA in human gastrointestinal tissues from several individuals. CYP3A mRNA is abundant in human liver and in mucosal epithelial cells of all segments of the human small intestine. RNA blot analyses showed that the mRNA species observed in most livers and in human small intestine represent CYP3A3/3A4 transcripts. This was confirmed at the protein level by immunoblot comparison of small intestine microsomes to in vitro expressed CYP3A4 and CYP3A5 proteins. In liver and small intestine, CYP3A mRNA is not uniformly distributed, with grain density highest in cells within the respective non-proliferative compartments. CYP3A mRNA was also observed in human oesophagus and colon. RNA blot analysis of multiple colons showed heterogeneity in the CYP3A mRNAs present. Two CYP3A mRNAs (CYP3A3/3A4 and CYP3A5) were detected in colon samples from several individuals. In addition to those localisation studies, the capacity of expressed CYP3A4 and CYP3A5 to activate the dietary heterocyclic amine MeIQ in the presence of alpha naphthoflavone was shown. These results show that there is considerable heterogeneity in the expression of the CYP3A subfamily in human gastrointestinal tissues. PMID- 7883228 TI - Unconjugated secondary bile acids in the serum of patients with colorectal adenomas. AB - A positive association between deoxcholic acid (DCA) in the serum and colorectal adenomas, the precursors of colorectal cancer has recently been found, which supported the hypothesis of a pathogenic role of DCA in colonic carcinogenesis. This approach was based on the hypothesis that DCA formed in the colon is absorbed into the portal venous blood and exhibits a constant spillover to the systemic circulation. To further substantiate this hypothesis this study investigated whether in the serum of adenoma patients DCA was higher in the unconjugated fraction, which originates directly from the colon. DCA was found to be 2.8-fold higher in the unconjugated fraction of patients with colorectal adenomas than in controls (0.89 v 0.32 mumol/l, p < 0.0025), 1.9-fold in the total DCA fraction (1.89 v 0.95 mumol/l, p < 0.0001), and 1.4-fold in the conjugated fraction (0.67 v 0.47 mumol/l, p < 0.05). It was further found that the bacterial isomerisation product 3 beta-DCA was twofold higher in the unconjugated fraction of adenoma patients than in controls (0.08 v 0.04 mumol/l, p = 0.27), 1.8-fold in the total iso-DCA fraction (0.11 v 0.06 mumol/l, p < 0.05), and 1.5-fold in the conjugated iso-DCA fraction (0.03 v 0.02 mumol/l, p = 0.68). The data suggest that the positive association between the serum DCA concentration and colorectal adenoma as described previously results from the DCA fraction that is absorbed from the colon. This further supports a pathogenic role of DCA in the carcinogenesis of colorectal cancer. PMID- 7883229 TI - Reporting simplified colonic transit studies using radionuclides: clinician friendly reports. AB - This study describes a graphic presentation of the results of a simplified segmental colonic transit model. This study requires three sets of images on three consecutive days after intake of indium-111 resin capsule at each time point. The per cent of ingested activity is calculated in each region of the colon and in the faeces. The program uses standard PC compatible graphic package, CorelDRAW (Corel Corporation). The report for the patients' notes consists of three schematic diagrams of colon with regions identified and a pot representing the faecal activity. The per cent of administered activity in each region and pot is both printed and represented by shades of grey (white representing 0% and black 100% activity), for each region and the pot. The distribution of activity is clearly seen at each time point and the report is presented on single A4 size sheet of paper. Using a simplified colonic study protocol it is possible to produce clinician friendly reports on a single sheet of paper. PMID- 7883231 TI - Natural history and prognosis of diarrhoea of unknown cause in patients with acquired immunodeficiency syndrome (AIDS). AB - This paper is a prospective study of patients with advanced human immunodeficiency virus infection and chronic diarrhoea for which no cause could be found after extensive investigations, including examination of multiple stool specimens for all known faecal pathogens and the histological examination of small and large bowel biopsy specimens. Of 39 such patients recruited from 155 prospectively investigated patients, eight had a possible cause of diarrhoea identified on follow up investigations, including small bowel neoplasms in three and cytomegalovirus in two. In 17 of the remaining 31 the diarrhoea resolved completely in a mean of seven months from its onset. Eleven had continuing mild or intermittent diarrhoea and three had more than 1 litre of diarrhoea daily for which no cause could be found. The median survival for patients with 'pathogen negative' diarrhoea was 48.7 months, which is similar to that of control patients with no diarrhoea and significantly longer than that of matched patients with a gastrointestinal pathogen (9.6 months). PMID- 7883230 TI - Prospective study of physical activity and the risk of symptomatic diverticular disease in men. AB - The relationship between physical activity and risk of symptomatic diverticular disease has not been investigated directly. This association was examined in a prospective cohort of 47,678 American men, 40 to 75 years of age, and free of diagnosed diverticular disease, colon or rectal polyp, ulcerative colitis, and cancer before 1988. During four years of follow up, 382 newly diagnosed cases of symptomatic diverticular disease were documented. After adjustment for age, energy adjusted dietary fibre, and energy adjusted total fat, overall physical activity was inversely associated with the risk of symptomatic diverticular disease (for highest versus lowest extremes, relative risk (RR) = 0.63 (95% confidence interval (CI) 0.45, 0.88). Most of the inverse association was attributable to vigorous activity, for extreme categories RR = 0.60 (95% CI 0.41, 0.87). For activity that was not vigorous the RR was 0.93 (95% CI 0.67, 1.69). Several specific activities were inversely associated with the risk of diverticular disease, but jogging and running combined was the only individual activity that was statistically significant (p for trend = 0.03). For men in the lowest quintile for dietary fibre intake and total physical activity (compared with those in the opposite extreme), the RR was 2.56 (95% CI 1.36, 4.82). Physical activity, along with a high fibre diet, may be an important factor in the prevention of symptomatic diverticular disease. PMID- 7883232 TI - Intraluminal gastric pH in chronic pancreatitis. AB - The aim of this study was to assess the circadian variations of intragastric pH in 28 inpatients with chronic pancreatitis (mean (SD) age 46.8 (12.4) years) and in 14 controls (45.4 (9.8)). pH Metry was performed using a monocrystalline antimony electrode placed in the body of the stomach under fluoroscopic control and connected up to a recorder (MKII Digitrapper, Synectics). The evaluation parameters, expressed as median and interquartile range, were: total period, postprandial periods (P1 and P2), interdigestive, and nocturnal phases. Patients with chronic pancreatitis were subdivided into three groups on the basis of severity of exocrine pancreatic insufficiency (secretin-caerulein test: lipase output at 60-90 min)--that is, those with severe insufficiency (chronic pancreatitis-SI: 13 patients, lipase output < 10% normal values and pancreolauryl test < 20%), those with only mild insufficiency (chronic pancreatitis-MI: seven patients), and those with normal secretion (chronic pancreatitis-NF: eight patients). The chronic pancreatitis-SI patients present significantly greater gastric acidification in the postprandial periods compared with controls (P1: p < 0.001; P2: p < 0.01), and with chronic pancreatitis-MI plus chronic pancreatitis NF subjects (P1: p < 0.01; P2: p < 0.05), taken together. In conclusion, gastric acidity, exocrine pancreatic insufficiency, and impaired digestion are closely related during the course of chronic pancreatitis. PMID- 7883233 TI - A variant alkaline phosphatase found in a case of gastric carcinoma with super bone scan. AB - A rare case of gastric carcinoma associated with increased serum variant alkaline phosphatase activities is presented. A 54 year old man had extremely high serum alkaline phosphatase activity (18,607 U/l) with normal calcium and phosphate concentrations. His bone scintigram showed abnormal findings, 'super bone scan'. He was diagnosed as having Borrmann type 4 gastric carcinoma with diffuse bone metastases by examinations of the upper gastrointestinal tract and iliac bone biopsy. The alkaline phosphatase isozyme of this patient was of the bone type as measured by cellulose acetate membrane electrophoresis and the placenta/bone type by agarose gel electrophoresis, respectively. Immunoelectrophoresis and the immunoprecipitation method using monoclonal antibodies against various alkaline phosphatase isozymes, however, showed that his serum alkaline phosphatase had the liver type antigenicity. Furthermore, it had a larger molecular size and different sugar chains compared with the common liver type alkaline phosphatase. These findings suggest that a unique variant alkaline phosphatase was produced by gastric cancer cells, which is possibly an explanation for the high serum alkaline phosphatase activities in this patient. PMID- 7883234 TI - Increased CA 125 in a patient with tuberculous peritonitis: case report and review of published works. AB - A case of a middle aged woman with weight loss, ascites, and a pleural effusion is presented where a clinical diagnosis of ovarian cancer was made. Her CA 125 was greatly increased at 873 IU/ml and the ascites was a lymphocytic exudate but cytology failed to show malignant cells. Operative biopsy showed numerous noncaseating granulomas in the omentum but no mycobacterial organisms were seen. Empiric antituberculous treatment was started before positive culture results were received and when treatment had ended both the ascites and pleural effusion had resolved and the CA 125 had fallen to 7 IU/ml. Review of published works showed several other examples of tuberculous peritonitis associated with increased CA 125 and the possible cause of raised CA 125 in this condition is discussed. PMID- 7883236 TI - Fatal infectious mononucleosis: a severe complication in the treatment of Crohn's disease with azathioprine. AB - A 19 year old man with a history of Crohn's disease treated with azathioprine and prednisone, died after a primary infection with Epstein-Barr virus. He had the characteristics of the virus associated haemophagocytic syndrome, a rare complication of viral infections, which consists of fever, constitutional symptoms, hepatosplenomegaly, liver function and coagulation abnormalities, and hypertriglyceridaemia. Additionally, there was pain, cytopenia, and histiocytic hyperplasia in the bone marrow, spleen, or lymph nodes. This severe complication has been reported previously in renal transplant patients, but not in those with inflammatory bowel disease taking azathioprine. The immunosuppressive therapy may have contributed to this fatal complication of infectious mononucleosis, and this complication should be considered when treating a patient with inflammatory bowel disease with azathioprine. PMID- 7883237 TI - Recurrent gastrointestinal bleeding associated with chronic pancreatitis. AB - A 52 year old man with chronic pancreatitis presented with recurrent upper gastrointestinal bleeding. Gastroscopy was normal, but visceral angiography suggested that there were gastric varices. Despite treatment with propranolol he had further episodes of bleeding and so underwent splenectomy to decompress the gastric varices. When the spleen was removed, however, an inflammatory mass in the head of the pancreas adherent to the posterior gastric wall was noted. Within it the splenic artery was visible and communicated with the gastric lumen through a small opening in the gastric wall. The artery was ligated and the patient has since had no further bleeding. Thus, chronic pancreatitis should be considered as a cause of recurrent upper gastro-intestinal bleeding, especially when gastroscopy is normal. PMID- 7883238 TI - Gastroenterological practice in Canada. PMID- 7883235 TI - Colitis ulcerosa complicated by malignant lymphoma: case report and analysis of published works. AB - A 51 year old woman with a two year history of ulcerative colitis developed a wide spread gastrointestinal non-Hodgkin's lymphoma of low grade malignancy (MALT lymphoma) involving upper and lower gastrointestinal tract, spleen, and bone marrow. After chemotherapy, clinical symptoms improved and lymphocytic infiltrates disappeared. Thirty nine cases of ulcerative colitis and 22 cases of Crohn's disease complicated by gastrointestinal lymphomas reported in published works are reviewed. In inflammatory bowel diseases any dense lymphocytic infiltrates seen in biopsy specimens obtained from ulcerative colitis or Crohn's disease should be assessed to exclude gastrointestinal lymphoma. PMID- 7883239 TI - Effect of long-term administration of melatonin on ultrastructure of pinealocytes in gilts. AB - We studied the ultrastructural changes in gilts' pineal gland after the oral administration of melatonin in dose 3 mg once daily (in ethanol vehicle) for 46 consecutive days. Appearance of the pinealocytes containing numerous secretory granules and an enlarged Golgi apparatus was the most visible effect of the melatonin administration. The melatonin treatment caused also some differences in the structure of pinealocytes with cytoplasmic dense bodies. The present results suggest that the orally administered melatonin had some effects on pigs' pineal gland. PMID- 7883240 TI - Morphometric ultrastructural study of satellite cells of rats during postnatal development (1st and 30th day of life). AB - Ultrastructural morphometric analysis of satellite cells of the diaphragm from one and 30-day-old rats was performed. The nuclear and cytoplasmic components of the cells were evaluated. The results obtained indicate that the satellite cells of one-day-old female rats are in a state of low activity. In 30-day-old animals, on the contrary, the cells are excited and active. This may be connected with their intensive participation in the process of development of the diaphragm muscle. PMID- 7883241 TI - Neuroendocrine component of different types of the pulmonary carcinoma. AB - One hundred and seventy lung tumors were examined: 155 squamous cell carcinoma, 12 adenocarcinomas and 3 mixed adenosquamous carcinoma. In electron microscopic examination the neuroendocrine cells were found: in 31 cases of squamous carcinoma, in 9 cases of adenocarcinoma, and 1 case of mixed adenosquamous carcinoma. PMID- 7883242 TI - Three dimensional analysis of thymic medulla. AB - In consecutive serial paraffin sections centers of gravity were defined for individual cross-sections of thymic medulla of the rat. Coordinates of the centers provided grounds for a three-dimensional reconstruction of thymic medulla using for the purpose computer techniques. In all cases the medulla exhibited continuity throughout the organ and showed dendritic character with up to IVth order branching. Moreover, analysis of thymic medulla structure allowed to exclude existence of a structure which would correspond to thymic lobuli. Apart from volume and area of the cortex and the medulla, lengths of the medulla and of its branches were determined. Statistical analysis of the results demonstrated that length of individual types of medulla branches was the least variable character of the thymus while the most variable one included area of the cortex and the medulla and their volume. All parameters describing volume and area of the thymic cortex/thymic medulla were found to correlate with each other. No significant relation was observed between the parameters on one hand and length of the medulla on the other. PMID- 7883243 TI - The development of the spinal accessory nerve in human embryos during 5th week (stages 14 and 15). AB - The spinal part of the accessory nerve was investigated in serially sectioned human embryos at developmental stages 14 and 15. It has been recognized that the spinal accessory nucleus extends through the upper 4 or 6 cervical segments of the spinal cord. The nucleus is formed by group of cells lying dorsolaterally to the primordium of the ventral horn. There is no continuation of the cells forming the spinal nucleus of the XIth nerve with primordium of the nucleus ambiguus. Extramedullary roots of the spinal accessory nucleus form a long trunk ascending into skull and uniting with vagus nerve. In one embryo at stage 15 the spinal accessory nerve separates at the level of the lower ganglion of the vagus. PMID- 7883244 TI - Cortical branches of the middle cerebral artery in human fetuses. AB - In 30 human fetuses, aged 20-31 weeks, the middle cerebral artery and its cortical branches were investigated with injection method. The cortical branches pass on the superlateral surface of the cortex and from a dense net communicating with corresponding vessels of the anterior and posterior cerebral arteries. PMID- 7883245 TI - Sources and variations of the arteries supplying the cervical part of the spinal cord in white rat. AB - Investigations were performed in 36 rats of Wistar strain. In 50% of cases the accessory arteries originating from the vertebral artery and connections of the ventral spinal artery with the first radicular arteries were found. The dorsal spinal arteries always originated from the intracranial part of the vertebral artery, and in many instances their discontinuity at the level of C4--C6 was observed. Besides the spinal arteries the cervical part of the spinal cord is supplied by radicular arteries which are more frequent in rats than in human. PMID- 7883247 TI - A comparative study of the utilization of ether- and ester-linked phospholipid containing liposomes by J774.E1 macrophage cell-line infected with Leishmania mexicana mexicana amastigotes. AB - The macrophage cell-line J774.E1 and Leishmania m. mexicana infection was used to investigate the uptake of liposomes, which differed in their bulk phospholipid: ester- or ether-analogue of phosphatydilcholine (PC). The receptor-mediated uptake of both species of liposomes, containing native or acetylated LDL as ligands was also evaluated. Uninfected and infected J774.E1 cell-line accumulated more ester- and ether-liposomes alone than mixed type (50:50, ester/ether). The utilization was significantly enhanced when both types of liposomes contained native LDL. The highest uptake was recorded for liposomes bearing acetylated LDL by infected J774.E1 cells. Accumulation of ester- and ether-liposomes with the same ligand was not markedly affected by different chemical nature of PC. Finally, ether-liposomes alone possessed certain activity against Leishmania m. mexicana amastigotes. The results presented here demonstrated the usefulness of ether-liposomes with specific ligands in site-specific delivery of antileishmanial compounds in vitro. PMID- 7883246 TI - Relationship between the intervertebral foramina and the spinal nerves at the level of C4-T2 of the human fetal vertebral column. AB - In 80 human fetuses of both sexes, aged 4 to 7 months the spatiality of the intervertebral foramina and the area of the cross-section of the spinal nerves at the level of C4-T2 of the vertebral column were investigated. It was found that the narrowness of the intervertebral foramen is not related to the sex of fetus. The most probable places for such narrowness are intervertebral foramina C4-C5 and T1-T2 on the right side and C7-T1 on the left side. PMID- 7883248 TI - Further description of blood stages of Plasmodium petersi from Cercocebus albigena monkey. AB - Additional information is given on the erythrocytic stages of Plasmodium petersi (Poirriez, Baccam, Dei-Cas, Brogan et Landau, 1933), which was found in a Cercocebus albigena monkey from the Central-African Republic. The first colour pictures of P. petersi are presented. In 60% of young trophozoites, the vacuole is divided into two or three parts by thin cytoplasmic streaks. In young trophozoites and almost mature schizonts, 80% of nuclei are oval or kidney shaped; they are two-coloured; measurement of their surface area shows that it is about twice that of the nuclei of P. gonderi at the same stages. Studies using polarised light show that most of the pigment granules are elongated (spindle shaped) and found at the periphery of old trophozoites and schizonts. P. petersi can easily be distinguished from P. gonderi and P. georgesi, the two other species found so far in Cercocebus monkeys, which are regarded as the African equivalents of the Asian macaques. PMID- 7883249 TI - Response of Ig-positive cells to Goussia carpelli (Protozoa: Apicomplexa) infections in carp (Cyprinus carpio L.). AB - The kinetics of Ig-positive cell populations in carp tissues was followed during an infection with the gut dwelling coccidian Goussia carpelli Leger et Stankovich, 1921. In cell suspensions of the anterior and posterior sections of the intestine, the proportion of Ig-positive cells increased with the development of the coccidia and peaked during oocyst formation at day 15 post exposure. These results suggest a reaction of the local mucosal immune system. In cell suspensions of pronephros the proportion of Ig-positive cells increased as well, indicating that a systemic immune response was also induced against this intestinal coccidian parasite of carp. PMID- 7883250 TI - Observations on the development of Syncuaria squamata (Nematoda: Acuariidae), a parasite of cormorants, in the intermediate and paratenic hosts. AB - The development of the nematode Syncuaria squamata (Linstow, 1883), a gizzard parasite of cormorants, was experimentally studied in the ostracod Notodromas monacha. After the eggs of this nematode have been swallowed by the ostracod, the toothed first-stage larvae of the parasite are released and penetrate through the intestinal wall into the haemocoel of the crustacean. Before attaining the infective third stage, the larvae moult twice in the body of the intermediate host (9-11 and 13-15 days after infection at water temperatures of 20-22 degrees C). The fishes Alburnoides bipunctatus, Noemacheilus barbatulus, Oncorhynchus mykiss and Poecilia reticulata were for the first time recorded as suitable experimental paratenic hosts of S. squamata third-stage larvae in which a slight growth of larvae may occur. The first recorded natural paratenic host of this nematode was tench, Tinca tinca, originating from a South-Bohemian pond where cormorants occur. Paratenic hosts are apparently the main source of S. squamata infection for cormorants. PMID- 7883251 TI - Dynamics of Anguillicola crassus (Nematoda: Dracunculoidea) infection in eels of Lake Balaton, Hungary. AB - Following the introduction of Anguillicola crassus into Lake Balaton, by 1991 the entire eel population became infected. At the same time, marked differences existed in the prevalence and intensity of infection between different areas of the lake. The highest prevalence values occurred in the eastern basin less densely populated with eels, while in the western basin a large proportion of the fish were free of infection. Helminth-free status accompanied by thickening of the swimbladder wall developed after intensive infections. In 1991, eel mortality could be observed only in the western basin. In 1992, the number of eels with swimbladders having a thickened wall but not containing helminths increased also in the central and eastern areas of the lake. Parallel to this, a mortality less expressed than the one in 1991 occurred in the central part of the lake. By 1993, a host-parasite equilibrium had become established in Lake Balaton. PMID- 7883252 TI - Present occurrence of Anguillicola novaezelandiae (Nematoda: Dracunculoidea) in Europe and its development in the intermediate host. AB - An examination of a sample of European eels, Anguilla anguilla (L.), collected from Lake Bracciano near Rome in 1993, the only known European locality with the occurrence of the introduced swimbladder nematode Anguillicola novaezelandiae Moravec et Taraschewski, 1988, revealed for the first time the presence of two Anguillicola species, A. novaezelandiae and A. crassus. In view of the investigations carried out by current authors in Bracciano Lake in the years 1982 1992, it is apparent that the latter species has been introduced into the lake quite recently, where it quickly became a dominant species. The development of A. novaezelandiae was experimentally studied in the copepod intermediate host, Cyclops strenuus, for the first time. The copepods were infected with nematode second-stage larvae at 21-22 degrees C; fully developed infective third-stage larvae were obtained 13 days p.i. The general morphology of individual larval stages of A. novaezelandiae was similar to that of larvae of the related species A. crassus. PMID- 7883253 TI - Modes of entry of the first-stage larvae of Elaphostrongylus cervi (Nematoda: Protostrongylidae) into pulmonate snails Arianta arbustorum and Helix pomatia. AB - Experimental infection of the pulmonate snails Arianta arbustorum L. and Helix pomatia L. with first-stage larvae of protostrongylid nematode Elaphostrongylus cervi Cameron, 1931 was performed in order to determine modes of larval entry into the body of the snail intermediate host. Groups by four individuals of both snail species were examined histologically 30, 60, 90, and 120 minutes after the beginning of exposure and 1, 2, 4, and 7 days post infection. All 64 snails examined were found to be successfully infected. The superficial furrows of the sole were recognized as the most important site of larval entry into the snail organism. Larval penetration was observed to be accompanied by destruction of the superficial epithelium. The number of larvae found in the subepithelial connective tissue of the headfoot was significantly higher than that found in other tissues and organs. Larval counts in individual parts of the body of snails examined from 0 to 7 days p.i. did not fluctuate significantly. The present results indicate that only those protostrongylid larvae which actively penetrated the superficial epithelium of the snail sole play an important role in the life cycle. PMID- 7883254 TI - Third-stage larvae of Daniconema anguillae (Nematoda: Dracunculoidea) in the subcutaneous tissue of eel Anguilla anguilla. AB - Daniconema anguillae Moravec et Koie, 1987 larvae measuring 1.64-1.76 mm were occasionally found in considerable numbers in the fins and subcutaneous connective tissue of approximately 50% of eel Anguilla anguilla (L.) sampled from Lake Balaton, Hungary. The larvae were noted for their slender body, very long tail with a rounded tip, a densely transversely striated cuticle, and the presence of boring tooth and large kidney-shaped amphids on the cephalic end. The larvae could easily be recovered from the above mentioned organs by placing them into isotonic saline solution. No disease signs or pathological changes attributable to the larval infection could be observed. The only histological indication of host reaction was the appearance of macrophages adhering to the body surface of larvae and of cells with spherical nucleus in areas around the larvae. A possible life cycle pattern of D. anguillae is discussed. PMID- 7883255 TI - Serum antibody profiles of Sarcoptes scabiei infested or immunized rabbits. AB - The circulating antibody profiles of rabbits infected or immunized with Sarcoptes scabiei var. canis were compared. Crossed immuno-electrophoretic analysis showed that infested hosts produced serum antibody to 12 proteins (antigens) in an extract made from sarcoptic mite bodies. In contrast, rabbits immunized with an extract made from mite bodies produced antibody to 20 Sarcoptes proteins (antigens). SDS-PAGE/immunoblot analysis revealed that serum from immunized rabbits contained antibodies that bound strongly to proteins of 25 and 39-52 kD that were only barely visualized by antibodies in serum from infested rabbits. PMID- 7883256 TI - Midgut hemagglutinins in five species of tsetse flies (Glossina spp.): two different lectin systems in the midgut of Glossina tachinoides. AB - Lectin activities were studied in five different species of tsetse flies. Different native or enzymatically treated human or animal red blood cells were used to detect hemagglutination activity in midgut extracts. Two inducible lectin systems in the midgut of G. tachinoides were distinguished. PMID- 7883257 TI - The ultrastructure of the intestinal microvillous border in the common vole (Microtus arvalis) naturally infected with Giardia microti. AB - The anterior jejunum from common vole naturally infected with Giardia microti (Kofoid et Christiansen, 1915) was examined by TEM and compared with the anterior jejunum from control (metronidazole-treated, Giardia-free) common voles (Pallas, 1778). Giardia microti infection resulted in significant diffuse shortening of microvilli and significant greater microvillous diameters. In addition, deformations of the microvilli were observed at the margin of the ventral disc. The microvilli attached to the lateral crest of the ventral disc were vesiculated with a disorganised filamentous core and contained whorled structures resembling "myelin-like figures". The findings are discussed in context of the Giardia epithelial cell interaction. PMID- 7883258 TI - Spirocamallanus rebecae sp. n. (Nematoda: Camallanidae) from freshwater fishes in south-eastern Mexico. AB - Spirocamallanus rebecae sp. n. is described from freshwater cichlids in some lakes of Southeast Mexico. It has 14 spiral bands in the buccal capsule, similar unequal spicules 503-544 and 281-297 long, 3 precloacal and 6 postcloacal pairs of papillae, vulva situated in the middle part of the body. An updated list of the species of the genus is presented. PMID- 7883259 TI - Two new species of the genus Goezia, G. brasiliensis sp. n. and G. brevicaeca sp. n. (Nematoda: Anisakidae), from freshwater fishes in Brazil. AB - Examination of freshwater fishes from the Parana River in southern Brazil during March 1992, revealed the presence of two new, previously undescribed species of the genus Goezia: G. brasiliensis sp. n. is described from the stomach of Brycon hilarii (family Characidae) (type host) and the intestine of Pseudoplatystoma coruscans (Pimelodidae) and it is characterized mainly by the length (0.802 mm) of spicules, number and arrangement of male caudal papillae (10 pairs of preanals and 4 pairs of postanals) and body measurements (male 11 mm, female 10-16 mm); the main characteristics of G. brevicaeca sp. n., described from the stomach of Brycon hilarii, are a short anterior intestinal caecum reaching anteriorly only to the posterior end of oesophagus, comparatively short spicules (0.367 mm), number of male caudal papillae (20 pairs of preanals and 4 pairs of post-anals) and an elongate, rather long body (male 17 mm, female 23 mm). PMID- 7883260 TI - Demodex agrarii sp. n. (Acari: Demodecidae) from cerumen and the sebaceous glands in the ears of the striped field mouse, Apodemus agrarius (Rodentia). PMID- 7883261 TI - Effect of repeated infestations of BALB/c mice with Ixodes ricinus nymphs on tick borne encephalitis virus infection. AB - The effect of repeated infestations of BALB/c mice with Ixodes ricinus (L.) nymphs on tick borne encephalitis (TBE) virus infection was studied. Enhancement of nymphal feeding, occurring in noninfected mice during the quaternary infestations, was less apparent or absent in female nymphs engorged on TBE virus infected mice. The mice infected with TBE virus during quaternary tick infestation survived significantly longer (P < 0.01) than mice infected with TBE virus during the primary tick infestation. The mean titre of virus in murine blood (determined by plaque assay) was significantly lower (P < 0.01) and the number of nymphs acquiring virus was reduced (P < 0.05) when feeding on hosts infected during the quaternary infestation. The results indicate that repeated infestations of I. ricinus nymphs on BALB/c mice, although enhancing tick feeding, reduced infection with TBE virus when inoculated intraperitoneally. PMID- 7883262 TI - [Organization of central interdisciplinary emergency admission. Immediate and subsequent aspects of highly developed preclinical management]. PMID- 7883263 TI - [Anticholinergic delirium--diagnosis and therapy]. AB - Anticholinergic delirium is a common side effect of various psychotropic drugs. The correct diagnosis is often delayed. The anticholinergic potential of many psychotropic agents is not known; it may become more manifest as a result of combination and cumulation effects. When the correct diagnosis has been established, a dose reduction or discontinuation of the drug involved may prove effective treatment. PMID- 7883264 TI - [Exogenous effects on ACTH and cortisol secretion]. AB - The availability of human corticotropic hormone, together with sensitive methods of measuring ACTH and cortisol have recently made possible studies on the mode of secretion of these hormones, secreted episodically and parallel in man, and exogenous factors modulating their liberation. Time of day, meals, physical activity and stress, lack of sleep and REM sleep all have an influence on the daily rhythm of their secretion. Phenytoin, ketoconazole, and cyproterone acetat modify the secretion of cortisol; opiates and diazepam inhibit that of ACTH. The liberation of CRH and ACTH is stimulated by the appetite suppressant, serotonin, and inhibited by the appetite-stimulating antagonist cyproheptadine and by glucocorticoids. PMID- 7883265 TI - [Differential diagnosis of Hepatitis A, B, C, D and E. Clinical, biochemical and viral serologic criteria. 3: Serology--hepatitis B]. PMID- 7883266 TI - [Intermittent self-ventilation. Therapy of chronic respiratory pump fatigue]. AB - Chronic fatigue of the respiratory pump may be due either to constant overexertion of otherwise healthy muscles of respiration (e.g. due to chronic obstructive lung disease, scoliosis) or to certain neuromuscular diseases (e.g. Duchenne type muscular dystrophy). Intermittent self-ventilation (ISV) is employed--in particular at night--in order to prevent imminent exhaustion of the respiratory muscles. The relief provided by ISV gives the muscles a chance to recover. The muscles of respiration can be largely rested by the use of volume controlled ventilation (IPPV), or partially rested by-BiPAP ventilation (Stimotron). Two main approaches to ventilation are available: non-invasive via a breathing mask or, if this is not possible, invasive ventilation via a tracheostomy. In addition to the commercially available standard nasal masks, we more often make use of custom-made so-called Grafschaft nose-and-mouth masks. The early provision of support for the muscles of respiration can obviate, or at least delay, the need for emergency intubation and subsequent assisted ventilation in an icu in endangered patients. PMID- 7883267 TI - [Drug therapy of migraine--a review of the literature]. AB - The medical treatment of migraine has two objective points: therapy for treating symptoms of an acute attack and prophylactic therapy for reducing frequency and severity of migraine attacks. A number of different therapeutic approaches for a symptomatic and a prophylactic therapy exists. The following article tries to give a survey of possible treatment strategies of migraine published within the last three years. PMID- 7883268 TI - [Therapy with immunoglobulins in neurologic autoimmune diseases. Indications and mechanism of action]. AB - Intravenous 7S-immunoglobulins (IVIg) are made of intact human IgG from pooled plasma by using cold alcohol fractionation followed by further purification steps to remove complement-activating material. The half-life of IVIg in vivo is approximately 3 weeks. Favourable effects were reported in patients with myositis and multifocal motor neuropathy who did not respond to established immunosuppressive therapies, and in Guillain-Barre-Syndrome and chronic inflammatory demyelinating polyneuropathy. No definite recommendation can presently be made concerning their use in other neuromuscular disorders and in multiple sclerosis where the results of ongoing and future controlled studies have to be awaited. Some of the possible mechanisms of immunoglobulin efficacy have been delineated in animal models and tissue culture: anti-idiotypic suppression, down-regulation of B- and T-cell activation, blockade of Fc receptors on phagocytic cells, neutralisation of superantigen and complement mediated effects, down-regulation of cytokine production and neutralisation of cytokines. Few side effects have been reported to date. However, treatment is expensive when compared with established immunosuppressive therapies. The main risk consists of the transmission of infectious agents that can only be excluded if the manufacturing process is optimal. A broad and uncontrolled use of immunoglobulins in the treatment of neurologic disorders is discouraged. PMID- 7883269 TI - [The cerebellum and cognition--psychopathological, neuropsychological and neuroradiological findings]. AB - It is a classical topic of clinical neurology that cerebellar dysfunctions give rise to motor deficits but spare the sensory and mental domains. Since the last century, however, cognitive decline occasionally has been attributed to diseases and lesions of the cerebellum. In recent years this assumption has gained in importance. The recent literature puts forward four arguments in favour of this suggestion: a) The neocerebellum has large reciprocal fibre connections with the association areas of the cerebral cortex. b) Functional imaging studies revealed activation of circumscript cerebellar regions during cognitive tasks. c) Patients with cerebellar malformations and diseases, respectively, may present with psychopathological signs and neuropsychological deficits. d) Atrophy of the cerebellum has been reported in schizophrenic and autistic syndromes. The present review aims at a critical evaluation of the relevant clinical and neuropsychological literature. So far there is no convincing evidence that lesions and diseases restricted to the cerebellum give rise to dementia or to impaired verbal and visual memory functions. With respect to specific perceptual tasks such as the discrimination of time intervals, problem solving, and visuospatial functions, no definite conclusion is possible so far. Some studies revealed cerebellar atrophy in schizophrenic and autistic patients. However, the functional relevance of these findings must be questioned since cytoarchitectonic alterations in extracerebellar areas, e.g. the basal forebrain, are present in these disorders as well. PMID- 7883270 TI - [In search of lost time--memory in dementia]. AB - With the progressing loss of coherent memory the world of the demented person dissolves into a succession of fragmented and incomprehensible situations. The resulting uncertainty leads to an increased need of self-assurance: in search of familiar surroundings and personal identity, the patient escapes into his preserved memories and begins to live in his past. Reminiscence may thus become a source of continuous strain to the persons entrusted with caring for the patient; on the other hand, it may as well open avenues to a deeper understanding of the patient and his world. PMID- 7883271 TI - [Red blood cell band 3: structure and function]. PMID- 7883272 TI - [Activation of neutrophil NADPH oxidase]. PMID- 7883273 TI - [Extra- and intracellular modulation of GABAA response]. PMID- 7883274 TI - Informative usefulness of age, sex and vital signs in the differential diagnosis of disturbed consciousness among 175 emergency outpatients. AB - Final diagnoses were determined among 175 emergency patients with disturbed consciousness with a Glasgow Coma Scale (GCS) of less than 15 and diagnostic usefulness of basic information was assessed using clinico-epidemiological indices. Subject patients included 98 males and 77 females with average age 53.4 years. Final diagnoses were as follows: intracranial lesions in 69 patients (39.4%), metabolic and systemic diseases in 97 (55.4%), mental diseases in 4 (2.3%), and diseases of unknown origin in 5 (2.9%). Cerebrovascular disorders and epilepsy were most frequent among the intracranial lesions, and poisoning, hypoglycemia, acute alcoholism and hypoxic encephalopathy among the metabolic and systemic diseases. Informative usefulness of age, sex and vital sings in diagnosing cerebrovascular disorders was analyzed with the use of ROC curves, showing that cut-off points of age over 60 years and of systolic blood pressure greater than 160 mmHg were most useful. PMID- 7883275 TI - Age-related increase in neuropeptide Y-like immunoreactivity in cerebrospinal fluid in women. AB - In order to investigate the age-related changes in neuropeptide Y (NPY) in cerebrospinal fluid (CSF) of men and women, we examined the concentration of NPY like immunoreactivity (NPY-LI) in CSF of a large population of Japanese men and women by specific radioimmunoassay (RIA). The dilution curve of CSF extract paralleled the standard curve of RIA for human NPY. Gel chromatographic studies revealed the presence of two peaks of NPY-LI, one emerging at the elution position of synthetic NPY and another emerging at a higher-molecular-weight position. NPY-LI in the CSF in 201 men (aged 17 to 69y) and 118 women (aged 17 to 69y) was 124 +/- 4 and 136 +/- 6 pg/ml (mean +/- SE), respectively. NPY-LI in the CSF of women, but not of men, increased significantly with aging. This finding suggests that the level of NPY with aging in the central nervous system (CNS) may be regulated somewhat differently in men and women. PMID- 7883276 TI - Ki-1 (CD30)-positive large cell lymphoma presented with leukemia: a case report. AB - A 77 year-old woman with Ki-1 positive large cell lymphoma who presented with leukemic phase of the disease is reported. She noticed general fatigue and fever in 1992 and was found to have anemia and abnormal lymphoid cells in the peripheral blood. The bone marrow was diffusely involved by these cells, differentials of which included acute megakaryocytic leukemia, malignant histiocytosis, and anaplastic large cell lymphoma. Immunophenotypic analysis showed that they were positive for CD3, HLA-DR, CD25 and CD30, but negative for CD4, CD8, CD19, FVIII and GpIIb/IIIa indicating Ki-1 positive lymphoma with T cell lineage. It may involve bone marrow, but leukemic phase of the disease is rarely seen. Therefore, it should be added to the differential diagnosis when large anaplastic or pleomorphic cells are seen in the bone marrow and/or peripheral blood. PMID- 7883277 TI - IgG & IgM antibodies against measles virus in unvaccinated infants from Pune: evidence for subclinical infections. AB - IgG and IgM class of antibodies to measles virus were estimated in the plasma samples of 211 unvaccinated infants living under overcrowded conditions in Pune, Maharashtra. IgG antibodies to measles virus, in high titres, were detected in 52.1 per cent and IgM antibodies in 31.3 per cent of the infants studied. Most of the infants with IgM antibodies to measles virus had not suffered from an attack of measles. A history of contact with an older child with overt measles was available for 13.3 per cent of the 211 infants studied. Among these infants with such a contact history, 82.1 per cent had IgM antibodies to measles virus. These observations suggest that many infants studied by us, had experienced subclinical measles infections and many times older children with measles at home or in the neighbourhood might have transmitted such infections. PMID- 7883278 TI - Effect of some new insect growth regulators on metamorphosis & reproduction of Aedes aegypti. AB - Fourth instar larvae and pupae of Ae. aegypti were treated with four most active insect growth regulators from a new series of mixed alkyl and aryl diethers based on geraniol. Considerable reduction in fecundity and fertility of adults was obtained. Treatment of pupae or pharate adults did not affect adult emergence. Topical treatment of adult females caused great reduction in fertility and fecundity in older as compared to younger females. In addition to the effects on reproduction, adult survival was also reduced in the treated younger females. PMID- 7883279 TI - In vivo localized proton magnetic resonance spectroscopy of intracranial tuberculomas. AB - In vivo proton magnetic resonance spectroscopy (MRS) was performed in ten patients with intracranial tuberculomas with the aim of finding biochemical finger prints which may help in the noninvasive diagnosis of the disease. Diagnosis of tuberculoma was confirmed in all these cases retrospectively. Ex vivo spectroscopy of formalin fixed samples of four granulomas and a normal brain (cerebellar) tissue, was performed to confirm the in vivo resonances. The in vivo study showed resonance at 1.3 ppm and 0.9 ppm assigned to methylene group (CH2)n and terminal methyl groups (-CH3) of fatty acids respectively which was subsequently confirmed by the ex vivo study. Large resonances of fatty acids in in vivo study appeared to be due to high lipid content of caseous material. It is concluded that in vivo proton spectroscopy may be helpful in differentiating tuberculomas from other intracranial mass lesions which have diagnostic difficulties on MR imaging. PMID- 7883280 TI - Long term effects of atenolol in patients of mitral stenosis & normal sinus rhythm. AB - We studied the effect of atenolol 100 mg/day in 50 symptomatic patients of mitral stenosis and normal sinus rhythm, in a placebo controlled study. Atenolol caused significant bradycardia as compared to placebo (vitamin C; P < 0.001) without any adverse effects. It also increased exercise capacity significantly as compared to placebo (P < 0.001). All the patients were followed up to the period of 9 months and no adverse effects were seen. We conclude that beta adrenergic blocking drugs like atenolol can be used as the only treatment for patients with mitral stenosis without congestive heart failure and in sinus rhythm, for long-term symptomatic relief. PMID- 7883281 TI - Prevention of ischaemia-induced biochemical changes by curcumin & quinidine in the cat heart. AB - Effect of myocardial ischaemia on the bioantioxidants levels in the cat heart was evaluated. In addition, effect of curcumin, an anti-inflammatory and anti thrombotic drug, and quinidine, a standard antiarrhythmic drug, was also studied in the cat. Myocardial ischaemia was induced by the ligation of left descending coronary artery. Quinidine (1 mg/kg, iv) was administered 15 min prior to while curcumin (100 mg/kg, ip) was given 30 min before ligation. Hearts were removed 4 h post coronary artery ligation. Levels of glutathione (GSH), malonaldelhyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and lactate dehydrogenase (LDH) were estimated in the ischaemic and non-ischaemic zones. Both the drugs protected the animals against decrease in the heart rate and blood pressure following ischaemia. In the ischaemic zone, after 4 h of ligation, an increase in the level of MDA and activities of MPO and SOD (cytosolic fraction) were observed. Quinidine and curcumin pretreatment prevented the ischaemia-induced elevation in MDA contents and LDH release. Curcumin pretreatment did not prevent the increase in MPO activity while quinidine did. Results obtained indicate alterations in the bioantioxidants following ischaemia and both curcumin and quinidine prevented ischaemia induced changes in the cat heart. PMID- 7883282 TI - Genetic marker profile of primitive Kutia Kondh tribal population of Phulbani district (Orissa). AB - Blood samples from 330 Kutia Kondhs (a primitive tribal population of Orissa) were subjected to a battery of tests for genetic markers to find out the incidence of various blood group polymorphisms (ABO, MN, Duffy, JKa), serum proteins, sickling and G-6-PD deficiency. Predominance of O (39.09%) blood group for ABO, N blood group (53.44) for MN and Fya+b+ (55.72) for Duffy blood group, were observed. High incidence of Hp2-1 (39.33), SS (70.43) and CC (96.65) for haptoglobulin, C3 and transferrin respectively were seen. The overall frequency of sickling was observed to be 16.36 per cent. The sex-wise distribution of G-6 PD was 13.71 per cent for males and 1.84 for females. PMID- 7883283 TI - Calcium activated neutral protease & calcium ATPase in glucose-6-phosphate dehydrogenase deficiency hemizygotes. AB - To study the mechanism of haemolysis in G6PD deficient erythrocytes, studies were undertaken in G6PD deficiency and in normal erythrocytes artificially loaded with calcium. Significantly increased concentrations of calcium, calcium activated neutral protease (CANP) and calcium ATPase were found in patients of G6PD deficiency. However, the membrane bound calcium, the total glycoprotein and sulphydryl groups of membrane were observed to be decreased. Similar results were also observed in the normal erythrocytes when loaded with calcium. These results point to the role of the proteolytic process in membrane modification, and altered membrane permeability during the haemolytic process. Our observations in G6PD deficiency and in in vitro point to the existence of a calcium dependent proteolytic preconditioning of erythrocyte accelerating the haemolysis. PMID- 7883284 TI - Increasing prevalence of human immunodeficiency virus infection among patients attending a clinic for sexually transmitted diseases. AB - Of 5883 patients screened during 1986 to 1993 in the sexually transmitted diseases (STD) clinic at a hospital in Vellore, south India, 105 (1.79%) were positive for human immunodeficiency virus (HIV) antibody. The prevalence of HIV infection increased from 0.26 per cent in 1986 to 2.64 per cent in 1993. In 1992 the prevalence was even higher, namely 3.94 per cent. The overall prevalence in these 8 yr was 1.98 per cent among men (n = 4392) and 1.21 per cent among women (n = 1491), the difference being statistically significant (P < 0.05). The prevalence in men rose from 0.36 per cent in 1986 to 4.24 per cent in 1992, and in women from 0 to 3.04 per cent during the same period. The major source of infection in men was female commercial sex workers, but among women it was mostly their husbands. The increase in prevalence of HIV infection is alarming, and indicates that the massive educational campaigns and other preventive measures have not resulted in decreased transmission. PMID- 7883285 TI - Intellectual environment, technical resources and curiosity: elements for competitive research. PMID- 7883286 TI - von Helmholtz (1821-1894) PMID- 7883288 TI - Cardiovascular responses to phenylephrine and sodium nitroprusside during acute coronary occlusion in dogs. AB - The effects of administration of pressor agent phenylephrine (PE) and depressor agent, sodium nitroprusside (SNP) (10-40 micrograms/kg) on arterial blood pressure (ABP) and heart rate (HR) were investigated during acute occlusion of left anterior descending coronary artery (LAD) in anaesthetized, artificially ventilated dogs with and without the influence of selective blockade of autonomic nervous system (ANS). ABP response to PE was significantly (P < 0.05) attenuated following 4 hrs of LAD occlusion in all the four groups of animals. SNP response at higher dose (40 micrograms/kg) was also significantly (P < 0.05) attenuated 4 hrs after LAD occlusion in ANS intact, beta-blocked and atropinized groups. The bradycardia response to PE after LAD occlusion was abolished in vagotomized group while in the other three groups, it was significantly attenuated following 4 hrs of LAD occlusion. The tachycardia response to SNP was significantly (P < 0.05) attenuated 4 hrs after LAD occlusion in ANS intact and atropinized animals. The response was abolished in beta-blocked animals and no significant change occurred (P > 0.05) in vagotomized group. This study suggests that the cardiovascular reflex effects of PE and SNP are significantly attenuated following acute LAD occlusion. Blocking any of the components of ANS changed this responsiveness. PMID- 7883287 TI - Drugs influencing cognitive function. PMID- 7883289 TI - Potassium channel blockade amplifies cardiac instability numerical studies of torsades de pointes. AB - Suppression of responses to premature stimulation has been the guiding principle in managing many cardiac arrhythmias. Recent clinical trails revealed that sodium channel blockade increased the incidence of re-entrant cardiac arrhythmias resulting in sudden cardiac death, although the physiologic mechanism remains uncertain. Potassium channel blockade offers an alternative mechanism for suppressing responses to premature stimuli. We have developed a simple model of a 2D sheet of excitable cells. We can initiate re-entrant activation with stimuli timed to occur within a period of vulnerability (VP). Reducing the Na conductance increases the VP while reducing the K conductance increases the collective instability of the array, and arrhythmias similar to torsades de pointes seen in patients subjected to K channel blocked can be readily initiated. Thus, while K channel blockade may suppress excitability by prolonging the action potential duration, it appears to simultaneously exhibit proarrhythmic properties that result in complex re-entrant arrhythmias. PMID- 7883290 TI - Cyclical mastalgia--is it a manifestation of aberration in lipid metabolism? AB - Several therapeutic and investigative studies suggest the possibility of the role of lipid profile aberrations in the pathophysiology of cyclical mastalgia. This prospective study is aimed to look for such aberrations. Fifty-seven patients of benign breast disease were included in this study who were symptomatic for at least 6 months prior to presentation. Detailed serum lipid profile work up was performed on day 1, 15 and 25 of menstrual cycle. The patients with symptoms of maximal severity (or limited to) during leuteal phase of menstrual cycle were included in group I (n = 32). Those who had mastalgia, but did not have above mentioned cyclical variation, were included in group II (n = 25). Since noncyclical mastalgia is a group of heterogeneous disorders of varied etiology, the patients in group II were treated as controls. At day 25, there was an elevation in mean values of HDL-C (P = 0.03) and HDL-C/LDL-C ratio (P = 0.01), and reduction in TC/HDL-C ratio (P < 0.03), in group I. This has not been the case with group II patients. When the patients of mastalgia were treated with low fat dietary regimen, there was a significant difference in the responses of these two groups (P value < 0.0001). Based on the results of lipid profile study and dietary intervention, we conclude that cyclical mastalgia is an entity which is distinctly different from noncyclical mastalgia and needs a different therapeutic approach. Our data, both investigative and therapeutic, suggests that cyclical mastalgia may be a result of cyclical aberrations in lipid metabolism, and the physiological treatment in the form of an appropriate dietary regimen holds a considerable promise. PMID- 7883291 TI - Effect of oral zinc supplementation on copper and haemoglobin levels in pregnant women. AB - In the present study, pregnant women in different trimesters of pregnancy were randomly allocated to untreated control group (Gp A; n = 58), and zinc treated group (Gp B; n = 104). Both groups were administered ferrous sulphate 60 mg, and folic acid 5 mg, twice daily throughout the period of study. Gp B subjects were also administered 45 mg elemental zinc, in a single daily post lunch dose. Maternal blood and urine samples collected in each trimester, and at the time of delivery, and blood taken from the umbilical cord were tested for Cu levels. Maternal Hb was also estimated. In Gp A, mean serum Cu increased significantly from 117.15 +/- 2.12 micrograms/dl in I trimester to 138.57 +/- 0.92 micrograms/dl in III trimester (P < 0.001). In Gp B, serum Cu declined significantly from 115.64 +/- 1.12 micrograms/dl in I trimester to 111.10 +/- 0.99 micrograms/dl in III trimester (P < 0.001). Urinary Cu declined significantly from 47.24 +/- 2.31 micrograms/24 hrs in I trimester to 37.43 +/- 2.06 micrograms/24 hrs in III trimester (P < 0.01). Zn treatment did not alter differentially the serum Cu levels in anaemic and normohaemic subjects. Gp B cord blood serum Cu was significantly lower as compared to respective controls, significance being proportional to duration of zinc administration. Hb levels increased significantly in all subjects. Increase in Hb in Gp B was significantly higher in comparison to that in Gp A (P < 0.05). Elemental zinc when administered to pregnant women in a dose of 20-45 mg/day, causes improvement in Hb level, without leading to hypocupremia. PMID- 7883292 TI - Some observations on clinical, cognitive and neurophysiological changes in subjects consuming indigenous alcohol. AB - Sixty-two subjects in age range of 25-50 years consuming more than 300 ml of alcohol daily, and an equal number of age matched non-alcoholic volunteers serving as control were tested. Their clinical and neurological evaluation, including electrophysiology was carried out. Their cognitive functions were measured using the modified WAIS system. In alcoholics there was a significant impairment of cognition, especially in orientation, attention and immediate recall. Their P300 wave was grossly abnormal as compared with the controls. Other electrophysiological investigations (EEG, NCV, EMG, BAER, VER) were normal. It is concluded that cognition may be grossly impaired in chronic alcoholics, which may not manifest clinically but is observed only after formal testing. PMID- 7883293 TI - Cyanide induced changes in dynamic pulmonary mechanics in rats. AB - Effect of subcutaneously (s.c.) administered potassium cyanide (0.5 and 1.0 LD50) and inhalation of hydrogen cyanide (55 ppm or 60.6 mg/m3) for 30 minutes was studied on various physiological parameters related to dynamic pulmonary mechanics in anaesthetized rats. Total pulmonary phospholipid with its fractions were also estimated. Both s.c. (1.0 LD50) and inhalation exposures increased air flow, transthoracic pressure and tidal volume accompanied by significant decrease in pulmonary phospholipids. Inhalation of hydrogen cyanide also exhibited direct effect on the pulmonary cells as evidenced by decreased compliance. The study suggests that inhalation of cyanide is more injurious compared to parenteral route. PMID- 7883294 TI - An evaluation of the assess peak flow meter on human volunteers. AB - The Assess peak flow meter was tested by comparing PEF values obtained on it for 49 normal subjects, with the values obtained for the same subjects on the Wright and mini-Wright meters. Its reproducibility was tested by comparing its coefficient of variation with that of the other 2 instruments. PEF values on the Assess were 5% lower in lower ranges and 9% higher in higher ranges tested as compared with those on the Wright. Values from the mini-Wright and Wright paralleled each other with the former values 3-5% higher. Variabilities on the Assess were 20-50% higher than those of the other 2 meters. Further, PEF values > 670 L/min could not be read by the Assess. Although the Assess fulfils necessary criteria for accuracy and reproducibility, it appears to be less reliable than the other 2 instruments, and its range limits and utility. PMID- 7883295 TI - Ketosis resistant diabetes of the young: a profile of its exocrine and endocrine pancreatic dysfunction. AB - A subset of insulin requiring diabetes in the young (IRDY) is ketosis resistant. Its pathogenesis and pathophysiology remain ill defined. The current study was done to evaluate the exocrine and endocrine dysfunction in ketosis resistant young diabetics. Fecal chymotrypsin (unit/G), basal & stimulated c-peptide levels (pmol/ml) and sonographic evaluation of the pancreas were done in 59 IRDY patients: 34 ketosis resistant (KR) and 24 ketosis prone (KP). Fecal chymotrypsin levels in KR (11.1 +/- 3.4) and KP (10.3 +/- 5.1) were lower than in controls (22.4 +/- 7.3) (P < 0.01). KR subjects had better endogenous insulin reserves than KP subjects: the basal and stimulated c-peptide levels in KR patients (0.12 & 0.17) were higher than in KP subjects (0.06 and 0.07) (P < 0.05). A strong correlation was noted between the exocrine and beta cell dysfunction in KR subjects (r = 0.7, P < 0.05). Pancreas was smaller in KR and KP patients than in controls (P < 0.05) on sonography. Thus the resistance to ketosis is a reflection of the better preserved beta cell reserves in the KR patients. Loss of the trophic effect of insulin and associated malnutrition is responsible for their exocrine dysfunction. PMID- 7883296 TI - Serum magnesium: a prognostic tool of acute myocardial infarction. AB - In an attempt to find the prognostic value of serum magnesium in various complications, serum magnesium was estimated spectrophotometrically, in patients of acute myocardial infarction. There was a statistically insignificant difference in serum magnesium levels of complicated group of patients (1.627 +/- 0.192 mg/100 mL) and those who had uneventful recovery (1.412 +/- 0.132 mg/100 mL). However, this difference was highly significant when compared between control group (2.514 +/- 0.16 mg/100 mL) and complicated and uncomplicated cases separately. It was also observed that serum magnesium levels were lowest in patients who died due to major arrhythmias and cardiogenic shock followed by patients who had arrhythmias (especially ventricular tachycardia) and pump failure. The routine use of iv magnesium is recommended within first few hours of acute myocardial infarction to reduce mortality, arrhythmias and pump failure. PMID- 7883297 TI - Influence of handedness on the visual and auditory reaction time. AB - Visual Reaction Time (VRT) and Auditory Reaction Time (ART) were measured in right-handed and left-handed human volunteers, using an Electronic Response Timer Unit. The study demonstrated that a group of left-handed women reacted faster (P < 0.05) with their left hand to an auditory stimulus than their counterpart using their right hand. VRT did not show any significant change within, and between, the groups and was not influenced by sex or age. The observed differences in ART may be due to central phenomenon. PMID- 7883299 TI - Cross reactivity of cephalosporins with penicillin. AB - Cross antigenicity of cephalosporins with penicillin has been studied experimentally and also by using serum from penicillin sensitive individuals. Definite hypersensitivity reaction was observed in all the animals sensitised with cephalosporins and challenged with penicillin except in rats. Cephalosporins could elicit reaction in tissues sensitised passively with serum obtained from penicillin sensitive individuals. PMID- 7883298 TI - Zinc levels in maternal and cord blood and in amniotic fluid--a possible marker for foetal malformation. AB - Zinc levels were estimated from the maternal and cord blood drawn at delivery and in the amniotic fluid drawn before delivery in 9 pregnancies resulting in congenitally abnormal foetuses and 21 pregnancies resulting in normal healthy babies. Zinc levels were significantly lower (P < 0.01) in maternal and cord blood serum in congenitally malformed babies as compared to healthy normal controls. Amniotic fluid zinc levels were significantly higher (P < 0.01) in pregnancies with malformed babies. The use of zinc levels as marker for foetal malformation has been suggested. PMID- 7883300 TI - Inhibition of tumour promotion in mice by eugenol. AB - Number of tumours (papillomas) produced by the application of 7,12-dimethyl benz (a) anthracene as initiator and croton oil promoter in mice were considerably inhibited (84%) by the prior application of eugenol. Moreover, there was considerable decrease in the number of tumour bearing animals and their onset. Eugenol inhibited superoxide formation and lipid peroxidation and the radical scavenging activity may be responsible for its chemopreventive action. PMID- 7883301 TI - Study on modification of hypoglycaemic effect of quinine by doxycycline in albino rats. AB - Hypoglycemia has been reported to occur in the patients and animals infected with various species of plasmodium (1). The use of quinine has been associated with significant decrease in blood sugar level, thus worsening the prognosis (2). In such a situation cautious thinking of possible drug interaction which may, further, aggravate the hypoglycemia is mandatory. But the data of the drug interaction of the combination of quinine and doxycycline in the treatment of chloroquine or multi-drug resistant falciparum malaria are not available. This study was aimed to find out whether this combination can cause more hypoglycemia when compared to quinine alone. PMID- 7883302 TI - Changes in the blood lipid profile after administration of Ocimum sanctum (Tulsi) leaves in the normal albino rabbits. AB - Administration of fresh leaves of Ocimum sanctum (Tulsi) mixed as 1 g and 2 g in 100 gms of diet given for four weeks, brought about significant changes in the lipid profile of normal albino rabbits. This resulted in significant lowering in serum total cholesterol, triglyceride, phospholipid and LDL-cholesterol levels and significant increase in the HDL-cholesterol and total faecal sterol contents. PMID- 7883303 TI - Effect of different feeding schedules on food intake in caudate lesioned rats. AB - Inbred albino rats were exposed to different feeding schedules before and after caudate nucleus lesions. The animals show adaptation to the new patterns of food deprivation even after caudate nucleus lesions. However, the lesioned animals are not able to elevate their food intake or body weight to the prelesion levels. These findings suggest that feeding, satiety and body weight mechanisms are disturbed in the absence of intact caudate nucleus, possibly due to removal of nigro-striatal dopamine influence. PMID- 7883304 TI - Influence of ranitidine on the hypoglycaemic activity of glibenclamide and tolbutamide in rabbits. AB - The influence of ranitidine on the hypoglycaemic activity of glibenclamide and tolbutamide was studied in rabbits. Ranitidine treatment (15 mg/kg, po, twice daily for one week) enhanced the hypoglycaemic activity of glibenclamide (40 micrograms/kg, po) while it has not altered either the hypoglycaemic activity or pharmacokinetics of tolbutamide (40 mg/kg, po) in rabbits. PMID- 7883305 TI - Influence of lateral posture on sweating: does posture alter the sympathetic outflow to the sweat glands? AB - Our unpublished observation that a lateral decubitus posture influences the pattern of sweating was systematically tested by measuring galvanic skin resistance (GSR). Changes in the GSR between two electrodes placed on skin was used to quantify the degree of sweating. In the lateral posture, sweating is inhibited on the lower half and stimulated on the upper half and reversal of the lateral posture induces sweating on the opposite half of the body. This observation suggests that the autonomic nervous system is controlled at least in part, by body posture. PMID- 7883306 TI - City health development. PMID- 7883307 TI - Variations in blood pressure of adolescents in relation to sex and social factors in a rural area of Haryana. AB - Adolescent students of a rural block were studied to find out variation in blood pressure in relation to sex, caste and socioeconomic status. Females had significantly higher mean values of blood pressure; both systolic and diastolic. There was significant variation in systolic blood pressure amongst adolescents of various socio- economic classes. Prevalence of systolic hypertension (95 percentile) was higher in adolescents of upper middle social class and diastolic hypertension in Prestige castes. It is suggested that screening for hypertension should be done at school leaving age and high risk adolescents should be advised about periodic check-up, proper diet, salt restrictions and exercise so that frank hypertension could be prevented in adulthood. PMID- 7883308 TI - Studies on victims of bite by a dog in Delhi. AB - Ninety persons were bitten by a single rabid dog on 23rd January, 1992 in Central Delhi area. All patients were given immediate first-aid, prophylactic tetanus toxoid injection and post-exposure antirabies treatment i.e., hyperimmune antirabies serum (ARS) and antirabies vaccination in different Hospitals of Delhi. Fifteen (15) patients received tissue culture antirabies vaccine (Rabipur or Verorab) and rest 75 patients were given nervous tissue vaccine. ARS was given to all patients as all had severe (Class-III) bite. Altogether there were 76 male and 14 female and 80 adult and 10 children bitten by the dog. All patients well tolerated the vaccines excepting a few, who developed very minor side-effects. Investigation regarding post-exposure antirabies antibody assessment were carried out in twenty-four patients at WHO Collaborative Centre for Rabies. Epidemiology for South-east Asia at National Institute of Communicable Diseases, Delhi. Paired blood samples were obtained from these patients and all of them had protective antibody titre (0.5 IU/ml) with mean titre of 1.81 IU/ml and 2.11 IU/ml in first and second samples, respectively. All patients were followed after six months and there were no death or vaccine failure reported. PMID- 7883309 TI - Tobacco smoking in a defined community of Delhi. AB - A Community based study was conducted in urban Delhi. It was found that Smokers constituted about 32 percent of adult males in Delhi Admin. Flats, Timarpur. Proportion of smokers was highest in 41-50 years age. 31 percent of school teachers were smokers. Out of all who tried to live-up smoking, 8 percent reverted back after abstinence of two year or more. About three fourth of the smokers were worried ill effects of smoking's on them and others. Significantly higher number of non-smokers expressed opinion for total stopping of advertisement and complete ban of sale of smoking tobacco. PMID- 7883310 TI - Artificial feeding practices in rural community--a cross sectional study in Warangal area (Andhra Pradesh). PMID- 7883311 TI - Perinatal mortality in eclampsia in relation to drug therapy. AB - Fifty-nine babies were born to eclamptic mothers among 7500 deliveries giving incidence of occurrence of 0.77 percent. The perinatal mortality in eclamptic babies was 32.7%, whereas the total perinatal mortality rate amongst all the deliveries was 10.5%. The mothers were treated within Group I--diazepam, Group II i chlorpromazine (largactil), phenargan and diazepam and Group III--largactil, phethidine and phenargan. The mortality rate was 23.8%, 18.8% and 66.6% respectively. The highest number of still-born i.e. six out of 8 occurred in Group III. Hundred percent still-born was noted in 28-32 weeks of gestation and birth weight less than 1.5 kg irrespective of drug regimes. Iargactil potentiates the respiratory depressant effect of pethidine and may cause high rate of still birth and death after birth. PMID- 7883312 TI - Evaluation of susceptibility status of Culex quinquefasciatus larvae to few organophosphorus insecticides based on logistic regression analysis. AB - A laboratory trial was carried out at Pune to evaluate the effectiveness of five types of larvicides viz. Malathion, Temephos, Fenthion, Dichlorvos and Fenitrothion against Culex quinquesfasciatus larvae. The expected number of mortality at various dose levels for the five types of insecticides were estimated separately using logistic regression model. Based on the fitted model, the estimated dose level corresponding to the 90 percent mortality (LC90) was obtained for each insecticide. Approximate 95 percent confidence intervals for the LC90 dose, in each case, has been provided. The analysis revealed that out of all the five types of insecticides included in the study, fenthion was the most effective. The estimated value of LC90 in this case was the lowest and is equal to 0.007 mg/L. The effectiveness of temephos, dichlorvos and fenitrothion was found to be approximately same and malathion was the least effective. The results were found to be comparable with that obtained under probit method. PMID- 7883313 TI - How do mothers recognize and treat pneumonia at home? AB - Two hundred mothers of children under five years of age having lower respiratory tract infection were interviewed with the help of pretested unstructured questionnaire to know the danger signs perceived by her in a child suffering from pneumonia and the home remedies used by them before seeking medical help. 'Pasli Chalna' and refusal to feed were the most common symptoms perceived as dangerous. 'Pasli Chalna' correlated with retractions in 91.9% and fast breathing in 8.1% cases. Honey (25%) and Ginger (27%) were the most common home remedies used for relief of cough. Self advised medications were used by 24% mothers and majority (58.4%) gained this knowledge from mass media. PMID- 7883314 TI - Hyponatremia in sick children: a marker of serious illness. AB - To study the association between hyponatremia (serum sodium < or = 130 mEq/L) and the final outcome of the illness, we correlated serum sodium concentration at the time of hospitalization with the length of hospital stay and mortality in a prospective study of 727 sick children aged upto 12 years, who sought emergency care. The mean +/- SE duration of hospital stay (7.7 +/- 0.4 days) among 217 children with serum sodium < or = 130 mEq/L was about 30% longer than that of 510 children with serum sodium > or = 131 mEq/L (5.9 +/- 0.3 days) (p < 0.01). This remained unaffected by the sex and the age group, but was further prolonged in children with hypotonic--euvolemic type of hyponatremia as compared to those with hypovolemic hyponatremia. The mortality rate in 510 children with normal serum sodium concentration (> or = 131 mEq/L) was 5.3%. In contrast, it was 17% in 47 children with serum sodium < 125 mEq/L (Relative Risk 3.2; 95% Confidence Interval 1.6-6.7) and 9.3% in 170 children with serum sodium between 126-130 mEq/L (Relative Risk--1.8; 95% Confidence Interval 1.1-3.7) (p < 0.01). Hyponatremia in acutely ill children at admission indicates a poor prognosis. PMID- 7883315 TI - Epidemiology, subgroups and serotypes of rotavirus diarrhea in north Indian communities. AB - To know prevalence of rotavirus diarrhea subgroups and serotypes, a prospective study was conducted in rural, periurban and urban communities at Chandigarh. Weekly surveillance for diarrheal episodes was carried out in 110 families each from rural, periurban and urban localities constituting 584 children < 5 years of age from October, 1988 to February, 1991. Stool samples of 218 diarrheal episodes occurring in 115 children were subjected to rotavirus detection by ELISA. Rotavirus positive samples were further analyzed for subgroups and serotypes using specific monoclonal antibodies. Overall prevalence of rotavirus diarrhea was 4.3% (25/584). Rotavirus constituted 11.5% (25/218) of total diarrheal episodes and 22% (25/115) among the children affected with acute diarrhea. Among rural, periurban and urban communities, the overall prevalences of rotavirus diarrhea were 7.3%, 3.2% and 2.3% and episode related prevalences of 31.8%, 7.4% and 5%, respectively (chi 2 test for trend was highly significant from rural to periurban to urban localities). Forty per cent (10/25 of rotavirus positive samples were subgroup I and 60% (15/25) sub-group II. Of the 25 rotavirus strains, 40% (10) were serotype 2, 24% (n = 6) serotype 3 and 36% (n = 9) serotype 4. No definite temporal or seasonal pattern of rotavirus was observed; however, more of rotavirus diarrheal episodes (16%) occurred during winter season. Subgroups and serotypes were observed to cocirculate during the rotavirus episodes. Demonstration of serotypes in our field study imply that the vaccine to be used in our country must be cross protective to have an effective impact on rotavirus infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883316 TI - Measles associated diarrhea and pneumonia in south India. AB - A prospective study was undertaken from April 1988 to April 1989, to assess the diarrheal and respiratory complications of measles. Standard definitions were used for the cases, Measles Associated Diarrhea (MAD) and Measles Related Pneumonia (MRP). Children with diarrhea not related to measles were recruited for comparison for MAD. There was a total of 454 cases, measles 53 (11.7%), measles associated diarrhea (MAD) 113 (24.9%), measles related pneumonia (MRP) 186 (41.0%) and MAD with MRP 102 (22.5%). Children under 10 months and 24 months were 11% and 51.5%, respectively. Altogether 215/401 (53.6%) and 288/401 (71.8%) had diarrhea and pneumonia. Children who had been measles vaccinated were 8.4%. The overall case fatality was 4.2%. Case fatality in pneumonia was 1.1%. There was no statistically significant difference between the MAD and diarrhea in relation to religion, water supply, the method of excreta disposal, nutritional status and immunization status other than measles vaccination. There was significant difference in the nature of stools between the two groups, the stools of MAD were more of dysenteric in nature (p < 0.005). Vitamin A deficiency as evidenced by eye signs, was significantly more in MAD than in diarrhea (p < 0.001). It is recommended that Vitamin-A be given to all children with measles, complication due to diarrhea be promptly and adequately treated and to consider measles vaccination earlier than 9 months. PMID- 7883318 TI - Rota virus diarrhea among infants and children at Tirupati. PMID- 7883317 TI - Assessment of knowledge and skills about growth monitoring amongst medical officers, child development project officers and multi purpose workers. PMID- 7883319 TI - Niemann-Pick disease type IS in sibs with 20 years follow up. PMID- 7883320 TI - The clinical value of a perinatal autopsy. PMID- 7883321 TI - Sirenomelia with spina bifida. PMID- 7883322 TI - Mothers' beliefs and practices regarding prevention and management of diarrheal diseases. PMID- 7883323 TI - Neutropenic enterocolitis with acute leukemia. PMID- 7883324 TI - Myelonecrosis in acute leukemia. PMID- 7883325 TI - Phantom hernia--an unusual manifestation of hypokalemia. PMID- 7883326 TI - An unusual case of kerosene oil poisoning. PMID- 7883327 TI - Neonatal ventilation--teething problems. PMID- 7883328 TI - Rare associations with Goldenhar syndrome. PMID- 7883329 TI - Pulmonary hydatid cyst an unusual presentation. PMID- 7883330 TI - Factors influencing survival in esophageal atresia. AB - There is little published literature from the third World countries that described the factors influencing survival of babies with esophageal atresia. We analysed 25 consecutive neonates treated for esophageal atresia. The overall survival rate was 36%. All 4 babies in Waterston Group A, 37.5% in Group B, and 15.4% in Group C survived. All 9 preterm babies died. Only 2 of the 16 babies who had pre-operative chest infection survived. The mean delay in diagnosis was 54 h in outborn babies and 20 h in hospital-born babies. We believe that a survival rate of 40% is easily achieved with minimum infrastructural inputs. Simple methods and practices that would vastly improve operative results have been suggested. PMID- 7883331 TI - Total thoracic stomach. PMID- 7883332 TI - Impact of nutrition and health education on rural pre-school children. AB - Pre-school children (n = 155) belonging to low socio-economic group from eight creches in villages around Chandigarh, were imparted nutrition and health education (NHE) for one year. Appropriate teaching material in the form of songs, rhymes and roleplays were scientifically developed for the purpose. For impact evaluation, objective tools in the form of checklists were formulated and used. NHE on three aspects, i.e., personal hygiene (PH), food hygiene (FH) and recognition of foods (RF) was imparted by Balsevikas (BSs) incharge of the creches, daily in a non-formal manner, for one year and evaluated periodically. On PH only, children of the lowest income group improved significantly. On FH and RF, all children registered significant improvement as these two aspects, were under the direct control of BSs who enthused and involved the children by providing an interacting and stimulating environment. The results are encouraging and indicate the pre-school children are educable in NHE provided participatory and appropriate material and methods are used. PMID- 7883333 TI - Diagnosis of tuberculosis current status. PMID- 7883334 TI - Meconium aspiration syndrome: recent concepts. PMID- 7883335 TI - Diabetes mellitus in infancy. PMID- 7883336 TI - Spinal cord injury in cephalic presentation. PMID- 7883337 TI - Congenital gingival granular cell tumor of newborn. PMID- 7883338 TI - Spontaneous gastric perforation in a neonate. PMID- 7883339 TI - Conjoined twins. PMID- 7883340 TI - ORS controversies and perspectives. PMID- 7883341 TI - Safe motherhood: when to begin. AB - Two thousand five hundred college girls were assessed for their knowledge and attitudes regarding sex, pregnancy and child rearing with the help of a pretested questionnaire. The site of menstruation was known to only 35.3% of the girls. The knowledge about the time and site of conception was 25.3% and 58.2%, respectively. Only 16.3% of the respondents knew the normal route of delivery although the duration of normal pregnancy was known to majority (87.7%). The girls were aware of the ideal timing of abortion (67.5%) but the safe method and legality were poorly known facts. Only 5% of the girls believed in pre-marital sex. More than half (54.9%) of the girls knew about some form of contraceptive, Copper-T being the best known. Nearly one fifth of the girls were either undecided or wished family members to decide about antenatal check-ups. The need for better diet and injections during pregnancy was well known although few (15.2%) were aware of the injections being tetanus toxoid. Only about 10% wanted a home delivery but one fourth felt that a Dai or a relative was suitable for conducting the delivery. An overwhelming majority of the students stated that knowledge about above facts was important and they would like to learn about them preferably during college education. It is recommended that 'Family life education' be provided during pre-adolescent and adolescent years to ensure a safe motherhood and a healthy child. PMID- 7883342 TI - An epidemiological study of congenital malformations in rural children. AB - Children between 0-6 years of age from six villages of Ambala District were screened for congenital malformations. Of 1371 children, malformations were observed in 30 (prevalence 22/1000). Twenty children had major malformations and six had multiple anomalies. Cardiovascular malformations were the commonest (37%) followed by musculoskeletal (30%), gastrointestinal (23%), central nervous system (13%) and genitourinary anomalies (6.6%). An etiological factor (maternal rubella infection or drug exposure during early pregnancy) could be ascertained in only 3 cases. Traditional birth attendents (TBA) and Anganwadi workers (AWW) were helpful in identifying 95% of the cases with externally visible malformations in rural areas. In majority of cases no remedial measures were taken by the parents. PMID- 7883343 TI - One year outcome of babies with severe neonatal hyperbilirubinemia and reversible abnormality in brainstem auditory evoked responses. AB - Brainstem auditory evoked responses (BAER) were longitudinally recorded prospectively in 18 term infants with neonatal hyperbilirubinemia (NHB) (total serum bilirubin > 15 mg/dl). Seven neonates had abnormal BAER. Wave complex IV-V was absent in eight recordings in NHB group while they were normal in the control group (p < 0.001). Prolongation of latency of waves I and V and interwave conduction time (wave I-V) occurred in jaundiced infants especially when unconjugated serum bilirubin level rose above 22 mg/dl. The abnormalities in BAER reversed to normal in all seven neonates after exchange blood transfusion indicating transient nature of bilirubin toxicity to the brain. All seven neonates in the study and control group had normal hearing, development quotient and were free of neurological sequelae on follow up for one year. PMID- 7883344 TI - Cord blood cortisol levels and respiratory distress syndrome. AB - Cord blood cortisol levels were analyzed in 121 neonates, using a "Coat a Count" RIA kit. Forty two appropriate for gestation age (AGA) preterms < 34 weeks who had not received antenatal dexamethasone constituted Group A, 32 AGA preterms < 34 weeks gestation who had received dexamethasone antenatally comprised Group B, while Group C consisted of 47 term normal neonates. Cortisol levels were compared in these 3 groups and correlated to the development of respiratory distress syndrome (RDS). It was observed tht preterms (Groups A and B) had significantly (p < 0.005) lower levels (8.45 +/- 6.31 micrograms/dl) compared to term neonates (11.67 +/- 4.68 micrograms/dl). Antenatal dexamethasone therapy did not significantly alter cortisol levels within the group of preterms. There was a significant difference (p < 0.02) in cortisol levels between those preterms who developed RDS (5.41 +/- 4.91 micrograms/dl) and those who did not (9.58 +/- 6.45 micrograms/dl). Preterms (Grous A and B) who did not develop RDS had cortisol levels comparable to term neonates. There was a significant reduction in the incidence of RDS (p < 0.05) in preterms who had received antenatal dexamethasone. Cord blood cortisol levels < or = 7 micrograms/dl had a positive predictive accuracy of 36.59% and negative predictive accuracy of 93.75% in predicting onset of RDS. PMID- 7883345 TI - Changing scenario of birthweight in south India. AB - Reducing incidence of low birthweight and increasing mean birthweights are now considered seriously in the national action plans. Comparison of birthweights obtained over two decades from the representative random segments of rural and urban areas of North Arcot Ambedkar district, Tamil Nadu, India, were studied. Although statistically significant (p < 0.001), the mean birthweight shows only a marginal increase of 70 g from 2774.5 g (+/- 500.2) in 1969-73 to 2845.4 g (+/- 451.0) in 1989-93. The mean birthweight stratified by area and gender also revealed similar increase. On the other hand, the proportion of low birthweight (< 2500 g) newborns reduced significantly from 27.2% to 15.9% in rural and 19.1% to 10.8% in urban area over the decades (p < 0.001). The increase in the mean birthweight and the decline in the percentage of low birthweight newborns over the years was greater in rural than the urban community, but the rural newborns continued to weigh lesser than their urban counterparts. PMID- 7883346 TI - Cerebrospinal fluid C-reactive protein in the diagnosis of meningitis in children. AB - C-reactive protein was evaluated in the cerebrospinal fluid of 250 patients to determine if its measurement is of any clinical value in the diagnosis of bacterial meningitis. The C-reactive protein was found to be significant in the diagnosis of bacterial meningitis. PMID- 7883347 TI - Are diarrheal incidence and malnutrition related in under five children? A longitudinal study in an area of poor sanitary conditions. AB - This study was conducted in Atali and Garkhera villages of Faridabad district of Haryana to assess the relationship between diarrheal incidence and malnutrition. Two hundred and fifty children in the age group of 6-47 months were followed up for one year from June 1988. History of diarrheal episodes was ascertained by fortnightly home visits. Nutritional status (weight for age) of the children was assessed at the beginning of the study and at every four monthly interval. The mean diarrheal incidence was 2.88 +/- 1.28 episodes per child year. The pre valence of moderate to severe malnutrition in the children was 35% out of which 8.8% were severely malnourished. Although severely malnourished children had 0.56 more episodes of diarrhea in a year compared to normally nourished, the difference was not statistically significant. Similarly, number of episodes of diarrhea also did not affect the subsequent nutritional status of the children. The possible reason for this could be that in areas of poor sanitary conditions, nutritional status may not play an important role in increasing the susceptibility of children to diarrhea. PMID- 7883348 TI - Immunization practices amongst pediatricians: a postal survey. AB - A postal survey regarding immunization practices amongst pediatricians was conducted. Out of 250 contacted, 108 responded (43.2%). The responders consisted of senior pediatricians, out of which 31 were serving or were retired Professors of Pediatrics from various Medical Colleges (27.7%). The survey showed that 20.4% give 3 doses of OPV during the first year, 18.5% give 4 doses and 61.1% give 5 doses. Only 11.1% give one "booster" dose of OPV, 72.2% give 2, 13% give 3 and 3.7% give 4 or more "booster" doses. Only 11.1% give "booster" doses upto the age of 2 years, 76.9% upto 5 year, while 12% give "booster" doses beyond the age of 5 years--some upto 14 years of age. Thirty six per cent advice 4 weeks and 36.1% advice 4-6 weeks interval between 2 OPV doses. Nearly one fifth (22.7%) give BCG "booster" doses upto 5 years of age and 6.5 give "booster" to adolescents. Thirteen per cent give Measles/MMR vaccines booster dose beyond the age of 2 years upto 16 years. This study shows that pediatricians follow different schedules and regimes for almost all the vaccines. Often similar schedules are not practised by pediatricians working in the same institutions. PMID- 7883349 TI - Present status of rotavirus vaccine. PMID- 7883350 TI - Surfactant therapy in neonatal respiratory distress syndrome. PMID- 7883351 TI - Who decides? PMID- 7883352 TI - Enteric fever--a changing sensitivity pattern, clinical profile and outcome. PMID- 7883353 TI - Drug availability and its utilization in Anganwadis. PMID- 7883354 TI - Prospect of splenectomy in thalassemia. PMID- 7883355 TI - Parenteral ciprofloxacin in persistent diarrhea. PMID- 7883356 TI - Pulse therapy in scleroderma. PMID- 7883357 TI - Sick sinus syndrome--a rare complication of typhoid fever. PMID- 7883358 TI - Recent concepts in management of nephrotic syndrome. PMID- 7883360 TI - Ultrasonographic normogram of fetal kidney circumference and fetal abdominal circumference ratio for early prenatal diagnosis. AB - Serial ultrasound scans were done in 300 fetuses between 16 to 24 weeks of gestation to establish the normogram of fetal kidney circumference (FKC) and fetal abdominal circumference (FAC) ratio (FKC/FAC). Of 300 fetuses, 150 fetuses were in the high risk group for fetal malformation and 150 patients were in the control group. The value of FKC/FAC varied from 0.27 to 0.30 from 16 to 24 weeks of gestation. No statistical difference was observed in the value of FKC/FAC in high risk and low risk (control) cases (p > 0.05). The value of FKC/FAC greater than or equal to 0.5 at 20 weeks or more was pathological for enlarged kidney. In 4 cases of multicystic kidney, the value of FKC/FAC ranged from 0.50 to 0.52 which was approximately 6SD above the normal mean ratio for that period of gestation. PMID- 7883359 TI - Pattern of acute renal failure at a referral hospital. AB - Fifty two children (upto 12 years age) with acute renal failure (ARF) admitted to the Nephrology services between January, 1989 to August, 1992 were studied to determine the cause and outcome. Of these, 39 were boys and 13 girls; 27 (51.9%) patients were below 4 years of age. Hemolytic uremic syndrome (HUS) was the commonest cause of ARF (30.8%) followed by acute tubular necrosis (ATN) in 28.84% and acute glomerulonephritis in 19.23%. All patients had severe renal involvement with anuria in 53.6% and oliguria in 46.4% at presentation. HUS was the leading cause of anuria (53.6%), followed by obstructive uropathy (21.4%). Thirty five patients required dialytic support for a median duration of 18 days (2-90 days). The mortality was 34.6%. Seven patients of HUS, 4 patients of ARF following surgery, 3 patients each of ATN and glomerulonephritis and one patient of obstructive uropathy died. Anuria at onset, central nervous system or respiratory complications and delay in institution of dialytic support were bad prognostic factors. We conclude that early referral and prompt institution of dialytic support may be helpful in decreasing the mortality. PMID- 7883361 TI - Norms for renal parenchymal volume in Indian children. AB - Seventy-seven clinically normal children with kidneys of normal size were examined sonographically. Renal parenchymal volumes were calculated and related to age, height, body weight and body surface area; growth charts were constructed. A significant correlation was found between the renal parenchymal volume and the body somatometric parameters. The present report thus provides norms for renal parenchymal volume in Indian children. PMID- 7883362 TI - Obesity and hypertension in children. AB - A study was conducted on two thousand five hundred and sixty school children to evaluate the prevalence of hypertension in apparently healthy school children of a prosperous, industrialized city of Punjab. The children belonged to 5-15 years age group of both sexes. The weight (kg) was taken by a standardized weighing machine while height was measured using a calibrated bar. For diagnosing obesity, the body mass index (BMI) was calculated by the formula: [formula: see text] A value of > or = 2.26 was considered as obesity. Blood pressure (BP) measurements were taken by a a mercury sphygmomanometer as per the recommendations of American Heart Association. Hypertension was diagnosed if blood pressure was more than 95th percentile for the age. Family history of hypertension was enquired from the parents of children. The BP of the hypertensive children was reassessed after six and nine months. The prevalence of hypertension was 2.8% at the first screening but decreased to 1.3% and 1.1% by 6 and 9 months, respectively. This fall was statistically significant (p < 0.01). There was no significant difference in the prevalence of hypertension between the two sexes. At the final screening, only children of 11 years or above were hypertensive. A statistically significant correlation with positive family history of hypertension was noted; 85.7% of hypertensive children had positive family history. The prevalence of hypertension was much higher in obese as compared to non-obese children (13.7% vs 0.4%). The correlation between obesity and hypertension was statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883363 TI - Carbohydrate malabsorption in acute diarrhea. AB - A group of 245 well nourished infants with acute diarrhea were screened for carbohydrate malabsorption by evaluating stool pH and reducing substances in the stools. Carbohydrate malabsorption was diagnosed in 28 cases (11%). Clinical features of carbohydrate intolerance were present in only one case. The duration of diarrhea after admission ranged from 1 to 13 days (mean 3.9 days). An oral lactose tolerance test was consistent with lactase deficiency in 32% of all cases. Thin layer chromatography showed many carbohydrates including monosaccharides in the stools, indicating that the defect in intestinal absorption was not specific for lactose. PMID- 7883364 TI - Pulmonary cavitatory tuberculosis in children. AB - This study was undertaken to analyse children with pulmonary cavitatory tuberculosis which is a rare and infectious condition. The pretreatment characteristics, course and response to three different anti-tuberculous regimes in 27 children with cavitary pulmonary lesions registered at the TB Clinic, Institute of Child Health, are described. Male:Female ratio was 1.2:4. Thirty per cent of affected children were below 3 years of age and had predominant lower lobe involvement whereas in older children the upper lobes were affected. Eighty five per cent of children had definite history of contact with an adult with tuberculosis. Tuberculin test was positive in 70% of children. Cavitary lesion were observed in the right lung in 66% of cases. Follow up and surveillance was carried out in 23 children who completed the anti tuberculous treatment. Regimes with isoniazid, rifampicin, pyrazinamide and streptomycin were given to different groups. Response and compliance was also monitored. Eleven out of 23 children had persistence of radiological lesions even after completion of 9 months of therapy. Inclusion of streptomycin with 2 or 3 bactericidal drugs in the intensive phase showed a better response. PMID- 7883365 TI - Breast feeding pattern in neonates. AB - The present study comprised 100 mothers of newborn babies with regard to their belief and practices about lactation. A vast majority (98.2%) of the mothers were breast feeding, 87.9% mothers used prelacteal feeds of one sort or the other. Only 0.5% breast fed their babies within 6 hours and nearly 50% started after 48 hours. Colostrum was discarded by 82.9% of mother and nearly 73% wanted to continue breast feeding beyond 1 year. The age of weaning preferred was after 1 year by 91%. Only 24.7% mothers had undergone antenatal check ups. Hence, much needs to be done with regards to proper antenatal care and advice to discourage wrong and harmful feeding practices. PMID- 7883367 TI - Cutaneous larva migrans in an infant. PMID- 7883366 TI - Infant feeding practices in Bombay slums. AB - A study was conducted in two slum areas in a Bombay suburb covering a total population of 4879. One hundred and fifty-three mothers having children below two years were interviewed. Ninety six per cent infants below the age of 4 months received breast milk, though exclusive breastfeeding was practised only in 37% infants. Timely complementary feeding rate was only 0.48. Twenty three per cent of mothers used bottle for administration of supplementary food or water. Only 15.7% of mothers used commercial milk formula and 8.5% used commercial weaning food. PMID- 7883368 TI - An outbreak of poliomyelitis in the Marathwada region of Maharashtra State: 1990. PMID- 7883369 TI - Nutritional status, social awareness and attitude towards marriage of adolescents in a tribal ICDS block of Himachal Pradesh. PMID- 7883370 TI - Marshall-Smith syndrome: a distinct entity. PMID- 7883371 TI - Microcytic hypochromic anemia in idiopathic pulmonary hemosiderosis: a diagnostic pitfall. PMID- 7883372 TI - Stressful family life events and parental perception of poor appetite in children. PMID- 7883373 TI - Schinzel-Giedion syndrome. PMID- 7883374 TI - Chediak-Higashi syndrome. PMID- 7883375 TI - Jarcho-Levin syndrome. PMID- 7883376 TI - Accidental dapsone poisoning in children. PMID- 7883377 TI - Present day concepts on promotion of breastfeeding in India. PMID- 7883378 TI - Undigested food presenting as bizarre objects in stool. PMID- 7883379 TI - Simpler tools for peritoneal dialysis of term newborns and young infants. PMID- 7883380 TI - Cerebral malaria vivax or mixed? PMID- 7883381 TI - Primary gastrinoma of the liver. PMID- 7883382 TI - Penile agenesis. PMID- 7883383 TI - Dermoid of the nasopharynx. PMID- 7883384 TI - Sedation in pediatric practice. PMID- 7883385 TI - Theophylline in childhood asthma. PMID- 7883386 TI - Haematological effects of pulse steroid therapy. AB - The aim of this study was to determine the haematological effects of 1 g methylprednisolone given intravenously as pulse steroid therapy (PST) to 10 cancer patients who had not received any chemotherapy or immunoactive drugs in the previous 3 weeks. Haematological values as determined with flow cytometry were evaluated before, and 1 and 24 h after, the pulse therapy. Total leucocyte count was found to be decreased at the first hour and significantly increased at the 24th hour, whereas total lymphocyte count decreased at the first hour and remained low at 24 h. CD4 lymphocytes were found decreased at the first hour whereas CD8 lymphocytes were significantly decreased at the 24th hour. The CD4/CD8 lymphocyte ratio and the values of haematocrit and platelets did not change significantly. The decrease in the total leucocyte count after 1 hour of steroid administration was notable, in addition to the results which were in accordance with previously reported data about steroid effects on haematological values. PMID- 7883387 TI - Fosfomycin distribution in the lower urinary tract after administration of fosfomycin trometamol salt. AB - Fosfomycin trometamol (FT) is a new fosfomycin salt with pharmacokinetic characteristics allowing hypothesis of its use in the single-dose therapy of lower urinary tract infections. In this study the diffusion of fosfomycin into bladder mucosa and urine after administration of a single oral dose of FT (3 g) was evaluated in patients affected by bladder or prostatic carcinoma having to undergo surgery. The administration of FT was scheduled in order to obtain blood, urine and tissue samples, to be collected during surgical operation at different times post administration. The peak concentrations in serum and bladder mucosa were detected within 3 h and 6 h respectively. Fosfomycin concentrations in bladder mucosa proved to be higher than the MICs of the most common urinary tract pathogens for at least 36 h. In urine, fosfomycin reached concentrations markedly higher than those found in serum and bladder mucosa, antibacterial levels lasting until the 48th hour post dosing. Fosfomycin trometamol, because of its pharmacokinetic and pharmacodynamic properties, appears to be suitable for single dose therapy of uncomplicated UTIs. PMID- 7883388 TI - Immune response in patients with intra-abdominal infections treated with carbapenems. AB - The immune responses against isolated microorganisms in patients with intraabdominal infections treated with meropenem or imipenem/cilastatin were investigated. Fifty-nine patients received meropenem 500 mg t.i.d. intravenously for 3-21 days (mean 5.4 days) and 50 patients imipenem/cilastatin 500 mg/500 mg t.i.d. intravenously for 3-17 days (mean 5.1 days). Three serum samples were taken from each patient, the first sample at admission, the second sample between three and seven days after start of antibiotic treatment, and the third sample between 14 and 28 days later. Ninety-eight per cent of the patients in the meropenem group and 95% of the patients in the imipenem/cilastatin group were cured. There was no difference in the clinical outcome between the two treatment groups. Escherichia coli, Bacteroides fragilis group, anaerobic cocci, Staphylococcus epidermidis, and Klebsiella spp. predominated among the isolated microorganisms. Thirty-nine patients in the meropenem group had significant immune responses against one or more of the isolated microorganisms while 31 patients in the imipenem/group had significant responses. E. coli and B. fragilis gave rise in antibody titres in most patients indicating that these species are the most important pathogens in intraabdominal infections. PMID- 7883390 TI - Pharmacodynamics and pharmacokinetics of Veliten (rutine, alpha-tocopherol and ascorbic acid) in patients with chronic venous insufficiency. AB - The aim of this study was to evaluate the pharmacodynamics and pharmacokinetics of a single oral dose of Veliten in 12 patients affected by chronic venous insufficiency. In particular, the pharmacokinetics of two components of Veliten, namely rutine and alpha-tocopherol, were considered, while with respect to pharmacodynamics, studies were made of venous function, haemocoagulative and fibrinolytic balance, and haemorheological parameters. Correlation between such changes and plasma drug levels was also evaluated. We found a significant increase of venous tone, venous capacity and venous distension after drug intake, as well as a significant activation of fibrinolysis (globally evaluated with euglobulin lysis time), related to a slight increase of plasminogen tissue activator. These changes appeared concomitantly with maximal plasma levels of rutine. We did not find any modifications of coagulative and haemorheological parameters. PMID- 7883391 TI - Metabolic Interactions, Nutritional Aspects, and the Immune System. 2nd International Heinz Nixdorf Symposium on Applied Immunology: Exercise and Sports of the German Federation of Sports Medicine. Paderborn, October 15, 1993. PMID- 7883389 TI - Influence of concomitant food intake on the gastrointestinal absorption of fluconazole and itraconazole in Japanese subjects. AB - The effect of food intake on the pharmacokinetics of orally administered fluconazole or itraconazole was investigated in a single-dose randomized two-way crossover study in Japanese subjects. 100-mg capsules of fluconazole or itraconazole were given to two parallel groups, each of 12 male and female volunteer subjects, and plasma concentrations of the antimycotics were determined by specific assays. Gastric pH and gastric emptying times were measured by coadministration of a radiotelemetric pH capsule. Intersubject variations in drug plasma concentrations were found to be much higher with itraconazole than with fluconazole. The coefficient of variation of the AUC (0-72) after food amounted to +/- 62% for itraconazole and +/- 16% for fluconazole. The consumption of a heavy breakfast significantly delayed the tmax of both drugs by approximately two hours (p < 0.05). This effect was accompanied by a significant prolongation of gastric emptying times (p < 0.0001). Food intake had essentially no effect on the absorbed amounts of fluconazole. The median relative bioavailability (postprandial vs fasting) based on AUC (0-72) was f = 0.99, with an individual range from 0.72 to 1.15. The corresponding Cmax ratio was 1.04 (range 0.91-1.17). The effect of food on the bioavailability of itraconazole was highly variable: it ranged from marked reductions (f = 0.35) to large increases (f = 3.74) of the AUC (0-72), at a median ratio of f = 1.23. The Cmax ratios postprandial vs fasting ranged between 0.27 and 5.71 (median = 1.04). It is concluded that food had an unpredictable effect on the extent of itraconazole absorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883392 TI - The immune system during exposure to extreme physiologic conditions. AB - It is not clear how the immune system is modulated in response to physical stress (e.g. trauma, surgery, burn and sepsis). In order to better understand the stress induced immune changes, effects of isolated stressors are evaluated. Human experiments include hypoxia, head-up tilt, hyperthermina and exercise, which influence all lymphocyte subtypes and especially so the natural killer (NK) cells. In essence, the immune response is enhanced even by light physical stress, but suppressed after prolonged, intense stress. PMID- 7883393 TI - Leucocytes, lymphocytes, activation parameters and cell adhesion molecules in middle-distance runners under different training conditions. AB - 20 young male track and field runners (400 m-3000 m) with a 4 mmol/l lactic acid threshold of x = 4.97 +/- 0.35 m/s were tested after three different training periods: 1. at the end of a two month endurance training, practised nearly every day; 2. after a period of speed and strength training, which was specific with respect to their discipline, with anaerobic lactic energy production up to 15 mmol/l lactic acid; 3. during the competition period. The blood samples were taken at rest (4 p.m.) and 22 hrs after the last exercise. On the cell surface the antigens CD3+, CD20+CD23+, CD4+HLADR, CD4+CD25+, CD8+CD28+, CD4+CD45RO+, CD16+CD56+, CD54+ and in the blood serum the concentrations of s-IL-2-R, s-ICAM-1 were analysed. 13 students of physical education served as a control group. The main results were: Only at the end of the endurance training period (1) an increase of s-ICAM-1 was found, which may be interpreted as a protective mechanism against infections. Compared with the control group CD20+CD23+ antigen was constantly elevated and during the transition from the training to the competition period the CD4+CD45RO+ subset increased. These results may provide evidence for a connection to a susceptibility to allergic disease and to overtraining. Furthermore, an activation of the specific immune system was indicated by an elevation of the s-IL-2-R and an activation of the monocytic phagocytic system was shown by increased levels of ICAM-1. The importance of these results for the training process and with regard to susceptibility to infections is discussed. PMID- 7883394 TI - Effects of aerobic exercise training on lymphocyte subpopulations. AB - This study was conducted to determine the effects of an aerobic exercise training program on subpopulations of lymphocyte phenotypes. Fourteen healthy but sedentary males, 18-40 years of age, were randomly assigned to either an aerobic exercise training or control condition. Aerobic exercise training consisted of three 45-minute sessions of cycle ergometry exercise per week at 70-80% of age predicted maximum heart rate for ten weeks. The aerobic exercise training resulted in a significant decrease in submaximal heart rate from 176 to 150 beats per minute to a fixed work rate of 150 watts (p < .01). This training effect was accompanied by increases in the resting level of the following lymphocyte subpopulations: CD2 (1717 vs 2183 mm3; p < .01), CD4 (942 vs 1280 mm3; p < .01), CD45RA+CD4+ (312 vs 595 mm3; p < .01), CD8 (655 vs 816 mm3; p < .05), and CD20 (162 vs 244 mm3; p < .01) cell counts. These findings indicate that several lymphocyte subpopulations are increased following a 10-week program of aerobic exercise training. PMID- 7883395 TI - Exercise, infection, and immunity. AB - In this article, emphasis was placed on the relationship between exercise and upper respiratory tract infection (URTI) in humans, experimentally induced infections in animals subjected to varying levels of exertion, and potential changes in the immune system that might explain the altered risk of infection. With regard to induced infections in animals, the influence of any exercise intervention appears to be pathogen specific, and dependent on the species, age, and sex of the animals selected for study, and the type of exercise paradigm. In general, although further research with larger subject pools and improved study designs is needed, published data at this time support a "J" curve relationship between risk of URTI and increasing exercise workloads. For example, individuals exercising moderately may lower their risk of URTI while those undergoing heavy exercise regimens may have higher than normal risk. Although researchers have investigated changes in immune function that might provide a biological rationale for the "J" curve model of infection and exercise, the wide variety of research designs, exercise protocols, subject characteristics, and methodologies combined with the innate complexity of the immune system have made interpretation of published findings equivocal. T and NK cell function, for example, is often reported to be decreased during recovery from high-intensity exercise. However, when adjustments are made for exercise-induced perturbations in blood lymphocyte subsets, any link to decreased host protection is unlikely. PMID- 7883396 TI - Biochemical mechanisms to explain immunosuppression in well-trained and overtrained athletes. AB - Glutamine is utilized at a high rate by some cells of the immune system (including lymphocytes and macrophages) and is essential for the viability and normal functioning of these cells. Experiments on lymphocytes in vitro showed that the proliferative response of these cells was dependent on the concentration of glutamine and this suggests that a decrease in plasma glutamine concentration could be responsible, at least in part, for the reported impairment of immune function in various conditions. Much of the glutamine that enters the body is utilized by cells of the small intestine, so that muscle is an important source for the plasma glutamine, Hence, the plasma concentration of glutamine represents a "metabolic link" between skeletal muscle and cells of the immune system. Indeed, the flux-generating step of glutamino metabolism in cells of the immune system is considered to be located in skeletal muscle which synthesizes and stores glutamine. The flux generating step is probably the outward transport of glutamine across the plasma membrane. The rate of this transport process and therefore glutamine release from muscle is decreased in conditions associated with a reduction in immune function or activity in the rat such as sustained exercise. The plasma glutamine concentration in man is decreased in a number of pathological conditions, with the largest decrease recorded following major burns. It is also decreased after prolonged exercise (e.g. marathon run) and in the overtrained state. It is suggested, therefore, that sustained physical activity could damage the glutamine release process so that it does not respond adequately to increased glutamine requirement by the immune system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883397 TI - Recruitment and recirculation of leukocytes after an ultramarathon run: preferential homing of cells expressing high levels of the adhesion molecule LFA 1. AB - The alpha L beta 2 (CD11a/CD18) integrin LFA-1 (lymphocyte function-associated antigen-1) mainly contributes to the firm arrest of leucocytes on the endothelium. Its cell surface density is thought to be important for the exercise induced homing of leucocytes. 9 athletes (7 males, 2 females, age 36-68 years, body mass 64 +/- 10 kg, height: 175 +/- 10 cm) absolved a competitive 100 km run in 8:07 hours (range: 7:29-9:50 hours). Immunophenotyping of circulating leucocytes and data acquisition by three colour flow cytometry before and up to 3 hours after the race showed that post exercise lymphocyte subpopulations with a higher expression of CD11a like CD3+CD8+CD45RO+ T-cells, natural killer cells (CD3-CD16/CD56+) and cytotoxic, not MHC-restricted T-cells (CD3+CD16/CD56+) decreased significantly more than CD45RO+ and CD45RO- helper-T-cells (CD3+CD4+), CD3+CD8+CD45RO-T-cells and B-cells (CD19+), which have lower levels for CD11a. Cell concentrations of regular monocytes (Fc gamma receptor 3 negative, LFA-1 low positive) increased, whereas mature monocytes (Fc gamma receptor 3 low or high positive respectively, LFA-1 high positive) decreased. In conclusion the surface density of the adhesion molecule LFA-1 on leucocytes is likely to contribute significantly to the extent of leucocyte's homing after long endurance exercise. PMID- 7883398 TI - Exercise and training: influences on cytotoxicity, interleukin-1, interleukin-2 and receptor structures. AB - Exercise responses are discussed with particular reference to the functional system involving interleukin-1, interleukin 2 and cytotoxicity. Prolonged endurance exercise causes an increase in plasma levels of interleukin-1, possibly as a response to muscle injuries, but plasma interleukin-2 levels generally fall. The latter change probably reflects stronger binding, consequent upon increased expression of p70-75 receptors for IL-2, and changes in the distribution or activity of target cells; IL-1 secretion may enhance the responsiveness of peripheral blood mononuclear cells, but prostaglandin secretion decreases their IL-2 production. Moderate exercise increases the cytolytic action of NK cells, but there is a prolonged fall of cytolytic activity after exhausting or psychologically stressful exercise; again these responses probably reflect altered IL-2 levels or receptor expression. Appropriately graded training reduces the adverse immune reactions associated with challenging exercise. Cross sectional comparison and training experiments both show an increased expression of p70-75 IL-2 receptors on the NK cells of active individuals. Moreover, moderate training reduces the exercise-induced suppression of IL-2 production. However, training that is pursued to the level of staleness, nutrient deficiency or muscle damage has a negative impact upon both the production of interleukins and the leukocyte response. Coaches must thus gauge training programs to optimize not only physiological function but also immune responses. PMID- 7883399 TI - The cytokine response to strenuous exercise. AB - Several groups have now investigated the cytokine response to strenuous exercise. In this article we try to summarize known data on this topic. Significant, albeit mild increases in plasma levels of the monokines IL-1, TNF-alpha, IL-6, and of soluble IL-2 receptor have been reported following strenuous exercise. Increased excretion of cytokines after exercise can also be shown in the urine of athletes. Modulation of cytokine release by strenuous exercise can also be demonstrated using in vitro cell cultures. Several authors have shown an increase in endotoxin stimulated monokine release following exercise. In contrast, using whole blood cultures we found strongly depressed production of interferon gamma (in response to mitogen or endotoxin) following strenuous exercise. The potential significance of cytokine modulation for exercise-related immunological problems is discussed. PMID- 7883400 TI - Physiology and biochemistry: influence of exercise on phagocytosis. AB - Phagocytic cells constitute the organism's first line of defence against external aggression. These cells carry out their non-specific defence function through what is known as the phagocytic process. This can be split up into several stages: adherence, chemotaxis, attachment, ingestion and killing of the foreign agent. The influence of exercise on the phagocytic process is dependent on the step considered, but in general, different responses have been observed in the adherence and chemotaxis capacities depending both on the intensity of exercise and on the phagocyte (neutrophil or monocyte-macrophage) studied. However, with respect to the attachment and ingestion of antigen, exercise generally induces an increase in every "situation", independent of the intensity of physical activity and the involvement of neutrophils or macrophages. The results with regard to the microbicide capacity that have been obtained up to the present time are very contradictory, showing perhaps a greater dependence on the phagocyte studied and on the intensity of exercise. This fact may be due to different methods used in the studies. One could conclude that exercise stimulates certain stages of the phagocytic process. This stimulation could counterbalance the decreased lymphoid activity after certain types of exercise that some authors have reported. PMID- 7883401 TI - Mucosal (secretory) immune system responses to exercise of varying intensity and during overtraining. AB - Athletes are susceptible to upper respiratory tract infection (URTI) during intense training and after major competition; high rates of URTI have also been associated with the overtraining syndrome (staleness). Secretory immunoglobulin A (IgA), the predominant immunoglobulin in mucosal secretion, is a major effector of resistance against pathogenic microorganisms causing URTI. Previous work has shown that salivary IgA levels decrease after a single bout of intense prolonged exercise. The purpose of these studies was to examine the IgA response to various exercise conditions. Whole, unstimulated saliva was obtained before and after exercise. IgA concentration (microgram.mg protein-1) was measured by ELISA and IgA secretion rate (microgram.min-1) calculated. Study 1: Recreational joggers ran on a treadmill for 40 min at 55% and 75% VO2peak and competitive distance runners ran for 90 min at the same intensites. In both groups, IgA secretion rate did not change significantly after exercise at either intensity. Study 2: Competitive runners ran on a treadmill for 90 min at 75% VO2peak on 3 consecutive days. IgA secretion rate decreased 20 to 50% after exercise (p < .001). Post exercise IgA secretion rates were significantly lower (p < .05) on days 2 and 3 compared with day 1. Study 3: Elite swimmers were followed over a 6 month season, with IgA concentration measured at 5 times. Throughout the season, IgA concentration was significantly (p < .05) lower in stale compared with well trained swimmers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883402 TI - Allergy and sports: exercise-induced asthma. AB - In some asthmatic subjects exercise is followed by a bronchospastic response that generally lasts 30-60 minutes and regresses spontaneously. The initiating stimulus is thought to be the cooling and/or dehydration of airways caused by hyperpnea. The mechanisms leading from thermodynamic changes to airway narrowing are object of controversy. Two hypotheses have been proposed, one suggesting that an increase in the osmolarity of airway lining fluid following water loss causes mediator release, and the other suggesting that an excessive vasodilation during airway rewarming causes vascular engorgement, thus reducing airway caliber. Other controversial issues in exercise-induced asthma are the role of airway inflammation and the question whether a late-phase response may occur. That inflammatory cells and mediators play a role is suggested by increased numbers of eosinophil and epithelial cells in bronchoalveolar lavage and by the efficacy of cromolyn and leukotriene antagonists in preventing EIA. The existence of late phase response to exercise is questionable because exercise does not cause an increase in airway responsiveness, which usually accompanies late-phase responses to allergens. Furthermore, data of bronchoalveolar lavage and bronchial biopsy suggest that the delayed broncho-constriction that may be observed after exercise reflects airway instability in subjects with more prominent eosinophilic inflammation of airways and is not specific to exercise. PMID- 7883403 TI - Healthy skin for all. International Committee of Dermatology. PMID- 7883404 TI - Associations of pemphigus and autoimmune disease with malignancy or thymoma. PMID- 7883405 TI - Contact pemphigus: a subgroup of induced pemphigus. PMID- 7883406 TI - Psychosomatic study of self-excoriative behavior among male acne patients: preliminary observations. AB - BACKGROUND: Studies of the psychosomatic correlates of self-excoriative behavior in acne have involved mainly women with acne excoriee. Little is written about the psychosomatic factors that affect men with acne. Excessive self-excoriation of acne lesions is an important clinical factor because it can prolong the course of the disease and exacerbate the deeper inflammatory process with an increase in the severity of scarring. METHODS: Thirteen men (mean +/- SE: age: 22.2 +/- 1.4 years) with mild to moderate facial acne, whose self-excoriative behavior was not severe enough to result in acne excoriee, completed a battery of self-rated questions assessing their self-excoriative behaviors, the severity of their acne, and various psychologic factors. RESULTS: Certain aspects of self-excoriative behavior (e.g., a tendency to pick or squeeze the acne lesions when stressed) correlated directly with depression (brief symptom inventory (BSI)) (Pearson r = 0.64, P = 0.02) and anxiety (BSI) (Pearson r = 0.61, P = 0.03) scores. The dermatologic indices of acne severity such as inflammation (Pearson r = 0.82, P = 0.0004) and pustules (Pearson r = 0.62, P = 0.03) were the strongest correlates of self-excoriative behavior. CONCLUSION: Self-excoriative behavior in men with acne may be exacerbated by a coexisting depressive or anxiety disorder. In contrast, women with acne excoriee have been reported to suffer from an immature personality where the cutaneous condition may serve as "an appeal for help." Men who excessively pick their acne will benefit from aggressive dermatologic therapies and should be assessed for underlying depressive and anxiety disorders. PMID- 7883407 TI - Alopecia areata and increased prevalence of psychiatric disorders. AB - BACKGROUND: The relationship between psychiatric disorders and alopecia areata has not been well studied. Although previous reports have been unable to correlate psychiatric illness with hair loss, a recent study determined that 74% of patients with alopecia areata (AA) under evaluation had one or more lifetime psychiatric diagnoses. METHODS: Two hundred and ninety-four community-based patients with alopecia areata responded to a detailed questionnaire distributed by Help Alopecia International Research, Inc. The prevalence of psychiatric disorders was determined using diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM-IIIR). RESULTS: Major depression, generalized anxiety disorder, social phobia, and paranoid disorder were all present in patients with alopecia areata at rates significantly higher than in the general population. CONCLUSIONS: Alopecia areata patients are at a higher risk of developing psychiatric comorbidity during their clinical course. PMID- 7883408 TI - Nature and treatment of delusional parasitosis: a different experience in India. AB - BACKGROUND: Delusional parasitosis has been described as a rare syndrome, often involving elderly women who respond poorly to treatment except to pimozide. METHOD: Nineteen cases of delusional parasitosis given antipsychotic treatment other than pimozide were followed up and the responses assessed in a structured manner. RESULTS: The frequency of the syndrome was higher than generally reported and the patients were younger and had been ill for a shorter period. There was good response to antipsychotic treatments using trifluoperazine, haloperidol, chlorpromazine, and electroconvulsive therapy, and 11 cases showed complete remission, five of them maintaining the recovery for more than 3 years. CONCLUSIONS: Delusional parasitosis is not as rare as described: it does not need to be chronic, and can involve young patients. Antipsychotic treatments other than pimozide are equally effective in delusional parasitosis especially if the patients are young and seen early in the illness. The frequency and nature of the disorder observed could probably be due to regional cultural factors. PMID- 7883409 TI - Giant vascular leiomyosarcoma. PMID- 7883410 TI - Coexistence of trichostasis spinulosa and eruptive vellus hair cysts. PMID- 7883412 TI - Dermatology and primary health care. PMID- 7883411 TI - Insecticide-induced lupus erythematosus. PMID- 7883413 TI - Skin-picking: the best cutaneous feature in the recognization of Prader-Willi syndrome. PMID- 7883414 TI - Effects of azelastin on pruritus and plasma histamine levels in hemodialysis patients. AB - BACKGROUND: Persistent pruritus is the most common symptom in hemodialysis patients. Its causes are poorly understood and there is no effective treatment. We have studied the effect of azelastin HCL on the plasma histamine concentrations and pruritus in maintenance dialysis patients with or without erythropoietin therapy. PATIENTS: Twenty-eight hemodialysis patients were divided into four groups according to the presence or absence of pruritus and whether or not they received erythropoietin therapy. RESULTS: Histamine concentrations in the patient groups were significantly higher than in healthy volunteers, but a significant difference could not be found among the four groups. The patients with pruritus showed no change in their histamine concentration during treatment with azelastin HCL, but their pruritus scores decreased remarkably. CONCLUSIONS: The present data do not support the thesis that the increased plasma histamine concentration is causally related to pruritus in hemodialysis patients or that the antiallergic drug, azelastin HCL, alleviates the pruritus of dialysis patients by decreasing plasma histamine levels. The possible role of the increased tissue levels of histamine remains to be studied. PMID- 7883415 TI - Leprosy illustration in medical literature. PMID- 7883416 TI - Skin immune system activation in pruritic urticarial papules and plaques of pregnancy. PMID- 7883417 TI - Treatment of psoriasis with topical aminophylline. PMID- 7883418 TI - Bilateral retinal detachment in Alezzandrini's syndrome. PMID- 7883419 TI - Verocay bodies in neurofibroma. PMID- 7883420 TI - Surgical pathology of the lower uterine segment caesarean section scar: is the scar a source of clinical symptoms? AB - A series of 51 hysterectomy specimens was studied to define the pathological changes that are present in the area of the post-caesarean section scar. An attempt was made to correlate these findings with the clinical symptoms that had led to the hysterectomy. Scar tissue, present for 2-15 years since the last caesarean section, contributed to significant pathological changes, including distortion and widening of the lower uterine segment (75%), "overhang" of congested endometrium above the scar recess (61%), polyp formation conforming to the contours of the scar recess (16%), moderate to marked lymphocytic infiltration (65%), residual suture material with foreign body giant cell reaction (92%), capillary dilatation (65%), free red blood cells in the endometrial stroma of the scar (suggesting recent hemorrhage) (59%), fragmentation and breakdown of the endometrium of the scar (37%), and iatrogenic adenomyosis confined to the scar (28%). These findings suggest that in some patients the anatomical abnormalities that develop in relation to the scar (especially the presence of a prominent congested fold of endometrium or the presence of small polyps) could give rise to clinical symptoms such as menorrhagia. In addition, inflammatory infiltration with fibrosis and distortion of the lower uterine segment could contribute to such symptoms as lower abdominal pain, dyspareunia, and dysmenorrhea. PMID- 7883421 TI - Reliability of tumor typing of endometrial carcinoma in prehysterectomy curettage. AB - The aim of this study was to determine the sensitivity and the specificity of tumor typing in the prehysterectomy curettage in order to assess the diagnostic accuracy in patients with endometrial cancer. Tumor typing was performed on complete prehysterectomy curettages of 154 patients with endometrial cancer treated during 1987-1991. The results were compared with the histologic findings of the hysterectomy specimen as the gold standard. Patients with no carcinoma demonstrable postoperatively in the removed uterus were excluded from the study. Tumor typing on prehysterectomy curettage revealed only a moderate sensitivity of 46-64%. In contrast, the specificity was > 90% for all histologic subtypes with the exception of the endometrioid tumor type (68%). The histologic subtypes (papillary, adenocarcinoma with squamous differentiation, mucinous, serous papillary, clear cell) achieved similar high predictive values despite a much lower prevalence due to the high values of specificity. Tumor typing of endometrial carcinoma based upon the findings of the prehysterectomy curettage reveals different reliabilities depending on the tumor type. PMID- 7883422 TI - Small cell neuroendocrine carcinoma of the endometrium. AB - Ten cases of endometrial small cell neuroendocrine carcinoma are described. The ages of the patients ranged from 50 to 75 years (mean, 64 years). Most of the tumors were bulky, intraluminal masses that invaded at least half of the myometrial wall. Small cells were the only malignant element in two tumors. In the other eight, there were admixed elements of adenocarcinoma (five), adenosquamous carcinoma (two), or heterologous mesodermal mixed tumor (one). Histologic examination of metastatic deposits in six cases revealed solely small cells in all but one. Immunohistochemical evidence of neuroendocrine differentiation was demonstrated in all tumors using the markers chromogranin, synaptophysin, leu-7, or neuron-specific enolase. Six of these tumors were originally interpreted as mesodermal mixed tumors with a homologous, stromal-type sarcomatous component at initial pathologic examination, but were reclassified as carcinoma. Clinical follow-up of these 10 patients and an additional seven well documented patients reported in the literature provided strong evidence for the aggressive nature of this neoplasm. Endometrial small cell neuroendocrine carcinoma is a rare, but aggressive neoplasm that can commonly be mistaken for a homologous-type mesodermal mixed tumor. PMID- 7883423 TI - Early pathologic stage clear cell carcinoma and uterine papillary serous carcinoma of the endometrium: comparison of clinicopathologic features and survival. AB - Clear cell carcinoma (CCC) and uterine papillary serous carcinoma (UPSC) are aggressive variants of endometrial carcinoma that may coexist or share some clinicopathologic features suggesting a similar biologic spectrum and the need for a common therapeutic approach. Twenty-nine cases of pathologic FIGO stage I and II CCC and 47 cases of FIGO stage I and II UPSC seen and treated at Yale-New Haven Hospital were reviewed, and the survival rates with regard to various pathological parameters were compared. Both groups of patients had similar clinical profiles with respect to presentation, age, weight, and medical problems. The 5-year survival for pathologic stage I patients with CCC was 72% and for those with UPSC 44%. The 5-year survival for pathologic stage II patients with CCC was 59% and for those with UPSC 32%. Analysis of survival showed that the depth of myometrial invasion, the presence of vascular space invasion, and the admixture of endometrioid features did not influence survival in either group of patients. In CCC, survival was also not influenced by the predominant histologic pattern, i.e., papillary versus nonpapillary. The results of this study suggest that early stage CCC and UPSC have similar clinicopathologic profiles, suggesting the need for aggressive approaches including a staging laparotomy and possibly similar therapy. However, the stage I CCC patients had a significantly better survival than the stage I UPSC patients. PMID- 7883424 TI - Malignant mixed mullerian tumor versus high-grade endometrial carcinoma and aggressive variants of endometrial carcinoma: a comparative analysis of survival. AB - To ascertain whether uterine malignant mixed mullerian tumors are biologically distinct from high-grade endometrial carcinomas (FIGO grade 3), we compared patient survival in 32 and 39 cases, respectively. The Cox proportional hazard model was employed to determine whether tumor type was an independent predictor of survival. The survival of patients with MMMT was also compared to that of patients with serous adenocarcinoma and clear cell carcinoma. The 5-year overall and disease-free survival were significantly lower for malignant mixed mullerian tumors (25% and 11%) than for high-grade endometrial carcinomas (64% and 56%). Using the Cox proportional hazard model, tumor type (MMMT vs. high-grade endometrial carcinoma) was a statistically significant predictor of survival after other important prognostic variables such as pathologic stage, depth of myometrial invasion, and vascular invasion had been taken into account. The increased aggressiveness of MMMT appears most attributable to their tendency to reach a more advanced stage by the time of clinical presentation and to their greater propensity for upper abdominal dissemination. The survival of patients with MMMT was also lower than that of patients with the special histologic variants of endometrial carcinoma, serous adenocarcinoma and clear cell carcinoma, which are recognized for their unusually aggressive clinical behavior. These results indicate that uterine malignant mixed mullerian tumors are clinically more aggressive than high-grade endometrial carcinomas and should continue to be recognized as a distinct entity. PMID- 7883425 TI - Proliferative and apoptotic status in endometrial adenocarcinoma. AB - The contribution of cell proliferation and apoptosis to growth patterns in endometrial adenocarcinoma were investigated. Immunohistochemical staining was carried out by an antibody for Ki-67 proliferative antigen, Ley apoptotic antigen, and oncogene products bcl-2 and p53. Forty cases of endometrial adenocarcinoma were classified as exophytic, endophytic, and mixed exo- and endophytic in light of their vertical growth pattern, and, in each case, the carcinomatous area was divided into three layers by its vertical axis. In all but one case, no zonal distribution of the antigen expression was observed. In one case, an exophytic tumor, Ki-67 expression was intense in the surface layer and Ley expression in the deep layer was also intense, suggesting a correlation between macroscopic growth pattern and cellular growth and apoptotic potential. However, in general, zonal distribution of cell proliferation and apoptosis could not explain the growth morphology of endometrial adenocarcinoma of the uterus and it was suggested that factor(s) other than cell proliferation and apoptosis determine macroscopic growth patterns. PMID- 7883426 TI - Microglandular hyperplasia of the cervix: a true "pill" lesion? AB - For many years, it has been assumed that microglandular hyperplasia (MGH) of the cervix occurs almost exclusively in women with endogenous (pregnancy) or exogenous (oral contraceptives) progestational stimulation, but this relationship has never been subjected to rigorous epidemiologic study. All available cases of MGH in our 1990 surgical pathology files were reviewed and clinical histories obtained. For each case of MGH, a control was chosen, consisting of a case in the same time frame of a woman of similar age who had undergone the same procedure (biopsy, conization, hysterectomy) for the same indication. A documented history of current oral contraception or pregnancy within the past 6 months was obtained in 57.9% (22 of 38) of the MGH cases and 47.4% (18 of 38) of the controls. This difference was not statistically significant by McNemar's test for paired data. The histologic features of the MGH lesions (lesion size, cytologic atypia, prominence of inflammation, and presence of solid component and of squamous metaplasia) were evaluated blindly without knowledge of the hormonal history. There were no statistically significant differences by the chi 2 test of association between cases with and without hormonal histories. This study provides no support for considering MGH or any of its constituent features. This study provides no support for considering MGH or any of its constituent features as causally related to oral contraception or other known hormonal perturbations. PMID- 7883427 TI - Primary vulvar sarcomas. AB - Vulvar sarcomas are uncommon, comprising only approximately 2% of all vulvar malignancies. Consequently, most reported series contain only a few cases. We add to the literature 10 cases of various primary sarcomas of the vulva, including previously unreported cases of angiosarcoma and a neoplasm resembling Ewing's sarcoma. The only histologic feature helpful in determining prognosis was tumor necrosis. PMID- 7883428 TI - Cervical cytology and conservative management of cervical neoplasias during pregnancy. AB - To elucidate the clinical significance of cervical cytology during pregnancy, 7,725 pregnant women were examined. Abnormal cytologic findings were recorded in 65 cases (0.8%). Colposcopically directed punch biopsies revealed cervical dysplasia and carcinoma in 27 cases (0.35%). The incidences in a massive examination for 714,119 women in Osaka Prefecture were 1.1% and 0.25%, respectively. Cytologic findings of the patients with cervical neoplasia during pregnancy agreed well (76%) with their histologic findings. Colposcopically, the squamo-columnar junction was visible in many cases, and white epithelium was most commonly observed during pregnancy. Pre- and postpartum follow-up study revealed that progression from dysplasia was seen only in two (20%) of 20 cases. Laser conization was performed on six women during pregnancy, and four were microinvasive carcinoma, all of which underwent normal vaginal delivery without any complication from conization. These results suggest that routine cervical cytology must be performed during pregnancy, and cytologic and colposcopic diagnosis may supply enough data to avoid unnecessary biopsies. Moreover, laser conization is recommended as an excellent diagnostic and therapeutic procedure for women with microinvasive carcinoma during pregnancy. PMID- 7883429 TI - Mucinous and clear cell adenocarcinomas of the endometrium in patients receiving antiestrogens (tamoxifen) and gestagens. AB - In recent years, tamoxifen therapy for breast carcinoma has been associated with endometrial carcinoma with increasing frequency. We describe 10 cases of this association as well as 12 cases of endometrial carcinoma after therapy with synthetic gestagens. All but one of the 22 carcinomas we describe here were of the mucinous or clear cell type, and arose in atrophic endometria containing foci of mucinous (endocervical) and clear cell metaplasia. In the endometrium, the antiestrogenic action of tamoxifen closely resembles the antiproliferative action of synthetic gestagens on the endometrium. In the endocervix, tamoxifen as well as synthetic gestagens, stimulate the endocervical mucosa to proliferate. In the endometrium, both tend to produce mucinous (endocervical) and clear cell metaplasia. A weak estrogenic action of tamoxifen may be expected to augment its own antiestrogenic gestagen-like action. Consequently, the antiestrogenic effect of tamoxifen is most likely responsible for the development of endocervical metaplasia and possibly corresponding endocervical and clear cell types of carcinomas within an atrophic endometrium. We believe that gestagen therapy administered to patients with endometrioid type carcinoma is contraindicated in patients with mucinous adenocarcinoma of the endometrium and that this is another reason to distinguish between these two types of carcinoma. PMID- 7883430 TI - IUD-associated pelvic actinomycosis: a report of five cases. AB - Five cases of intrauterine device (IUD)-associated tuboovarian actinomycosis are presented. The patients' ages ranged from 33 to 49 years and their IUD usage from 2 to 12 years. Clinical features of the cases included stenosis of the sigmoid colon in 4 cases, ureteric or bladder obstruction in two cases, and rectal fistula in a further instance. All patients were successfully treated postoperatively with penicillin or ampicillin. An initial diagnosis of ovarian carcinoma was considered in all cases. Although Actinomyces is difficult to differentiate histopathologically from microorganisms and other substances that cause the Splendore-Hoeppli phenomenon, morphological diagnosis permits a quicker and more practical approach than bacterial cultures in the establishment of postoperative antibiotic treatment. Intraoperative frozen-section diagnosis of an acute inflammatory process permits the surgeon to make an immediate decision in order to avoid extensive surgery when ovarian carcinoma is suspected. PMID- 7883431 TI - Primary squamous cell carcinoma of the endometrium: a case report and a suggestion of new histogenesis. AB - A case of primary endometrial squamous cell carcinoma (ESCC) in a 75-year-old woman is reported. In her endometrium, mature stratified squamous epithelium was associated with mucinous glands in which epithelium and glands were identical to those of the uterine cervix, but which were not connected with the cervix. Thus, the endometrial squamous epithelium with mucinous glands was diagnosed as heterotopic cervical tissue. This heterotopia was surrounded by ESCC and connected with it. The present case suggests that some ESCCs may arise in heterotopic cervical epithelium in the endometrium. PMID- 7883432 TI - Uterine atypical polypoid adenomyoma and ovarian endometrioid carcinoma: metastatic disease or dual primaries? AB - Atypical polypoid adenomyoma (APA) is an uncommon uterine tumor that rarely metastasizes, although it closely resembles a well-differentiated endometrioid carcinoma. A 37-year-old woman with a history of pelvic endometriosis and oral contraceptive use developed an APA and later presented with bilateral ovarian endometrioid carcinomas. DNA ploidy analysis and human papilloma virus (HPV) typing of the APA and ovarian carcinomas were performed to characterize the primary or metastatic nature of the tumors. Both tumors were aneuploid. The APA had a DNA index of 1.53, compared with 1.19 for the ovarian carcinoma. The APA contained HPV 18, and the ovarian carcinoma a mixed infection of HPV 6, 11, 16, and 18, with types 6 and 11 predominating. These differences in DNA index and HPV type supported the autonomous nature of the APA and the ovarian carcinomas. The report affirms the benign outcome of APA, highlights its complication by a second malignancy, and suggests an etiological role for endometriosis, steroid hormones, and possibly the HPV in the formation of one or both tumors. PMID- 7883433 TI - Borderline and malignant serous tumor arising in pelvic lymph nodes: evidence of origin in benign glandular inclusions. AB - This report describes two cases of malignant serous cancers with areas of borderline malignancy, which appear to have arisen within benign glandular inclusions of coelomic origin in pelvic or para-aortic lymph nodes. The patients were 44 and 62 years of age. In both cases the nodes contained benign glandular inclusions lined by a single layer of epithelium which resembled that of tubal epithelium. The location of the glandular epithelium varied from within the fat near the node to intracapsular, subcapsular, or interfollicular positions. The number of glands ranged from few to extensive. In both cases the glandular inclusions disclosed epithelial proliferations, ranging from minor degrees of stratification with formation of small papillae of atypical cells (borderline serous tumor) to almost solid tumor typical of serous cancer. In both cases, the borderline and cancerous tumors exhibited areas of transition which appeared to arise from benign glands. Although benign glandular inclusions of coelomic origin are well documented to occur in pelvic or para-aortic lymph nodes of 5-20% of women and have been considered to be of significance only because of the possibility of the misdiagnosis of cancer, it should now be recognized that the glandular inclusion cysts themselves can become neoplastic. PMID- 7883434 TI - Localization of the major immunogen and other glycoproteins of the louse Polyplax spinulosa. AB - A 31-kDa.immunogenic glycoprotein of Polyplax spinulosa was localized on louse sections using indirect immunofluorescence with specific antibodies of louse infested rats and using fluorescein-labelled lectins. Antibodies of infested rats reacted specifically with midgut epithelium and semi-digested content of the gut. They did not bind to other louse tissues including salivary glands. The lectins concanavalin A and wheat germ agglutinin bound strongly to the immunogen, the gut and its semidigested contents. Electrophoretic and blotting analysis showed the presence of a 31-kDa glycoprotein component reacting with specific rat antibodies, concanavalin A and wheat germ agglutinin in louse faeces. The result indicates that the 31-kDa immunogen is secreted by the midgut epithelium into the gut lumen and faeces. We suggest that rats become immunized by scratching the lice faeces into the skin. PMID- 7883435 TI - 5-hydroxytryptamine-immunoreactivity in the monogenean parasite, Entobdella soleae. AB - 5-HT-immunoreactivity in Entobdella soleae was found to be extensive throughout both the central and peripheral nervous systems, with the strongest staining occurring in the innervation of the forebody, most notably in the paired cerebral ganglia, pharynx and adhesive pads. In the reproductive system, staining was evident throughout the numerous cell bodies and fibres innervating the musculature of the egg-assembly apparatus. The haptor contained an extensive array of serotoninergic fibres derived from the main longitudinal cords; this array was associated with the haptoral muscles and sclerites, and possibly with the ventral sensory papillae. PMID- 7883436 TI - Ultrastructure of sperm and spermiogenesis in the monocotylid monogeneans Monocotyle helicophallus and Calicotyle australiensis (Platyhelminthes). AB - Spermiogenesis in Monocotyle helicophallus involves formation of free flagella which rotate to lie parallel before fusing. There is no median cytoplasmic process. A small number of microtubules (usually 2-4) is associated with the axonemes in the zone of differentiation. Nucleus and a fused mitochondrion migrate alongside the axonemes and one basal body moves distally. A coil of nucleus, originally in the cytophore, also moves out along the shaft. The mature spermatozoan has only a single axoneme for a short distance at each end, with two associated microtubules at the proximal end, as well as one axoneme, nucleus and mitochondrion throughout most of its length (the nucleus being enlarged and roughly coiled in one region), and a short region of two overlapping axonemes. We interpret our findings as two axonemes arranged almost end to end, one extending from the proximal end to some point in the mid-region, where the second axoneme begins and continues to the distal end of the sperm. Spermatozoa of Calicotyle australiensis develop from a zone of differentiation which has two basal bodies and a complete ring of cortical microtubules. Two initially free axonemes fuse with each other and there is no median cytoplasmic process. Spermatids form within parallel canals in the cytophore, by backward movement of the zone of differentiation. Prior to detachment, an electron-dense spiral end-piece forms around and proximal to the basal body region. Sixty-four spermatids are present in each isogenic group. With the study of spermiogenesis in more species of Monogenea Monopisthocotylea, it is apparent that the previously designated sperm patterns 2 and 3 are not distinct and should be combined and re-defined. Species previously designated as having sperm patterns 2 and 3 can all be accommodated by the description "two normal axonemes or one normal and one shortened, altered or displaced axoneme, and none, one or a few cortical microtubules remaining in a region of the sperm derived from the zone of differentiation in which a few or a complete ring of microtubules was present". PMID- 7883437 TI - A tropical assemblage of ectoparasites: gill and head parasites of Lethrinus miniatus (Teleostei, Lethrinidae). AB - Aspects of the community ecology of metazoan ectoparasites of Lethrinus miniatus (Teleostei. Lethrinidae) from 3 localities on the Great Barrier Reef were examined. Twelve species of Monogenea, 6 of Copepoda, 2 species of adult and several larval Isopoda and 1 leech were found. Total parasite numbers reach 3500 per host, and prevalence of infection with a particular parasite species reached 100% in some species. Numbers of parasite species per fish varied from 5 to 11. Four parasite species were most dominant on different fish if intensities of infection were used to calculate dominance, one species representing about 80% of all parasite individuals on a particular fish at 2 localities and about 50% at the third locality. Ten parasite species were most dominant on different fish, if volume (biomass) was used for calculating dominance, one species representing about 55% at one and 80% of total parasite volume at 2 localities. Parasites included at least 12 congeneric species of 4 or more genera, and those (of 2 genera) occurring on the gills showed much overlap in their distribution. Congeneric Monogenea of the families Dactylogyridae and Diplectanidae occurring in the same sites differ markedly in the size and structure of their copulatory sclerites. Positive associations between species were much more common than negative ones. The bony parts of the gills (gill arches) were never found to be infected, indicating the availability of empty niches. PMID- 7883439 TI - A PCR strategy for the isolation of glutathione S-transferases (GSTs) from nematodes. AB - Anchor based PCR technology has been used to isolate a GST sequence from the gastro-intestinal nematode Heligmosomoides polygyrus. A 800 base pair product was amplified from first-strand cDNA using primers based on the N-terminal sequence of purified H. polygyrus GST (upstream primer) and a non-specific polyadenylate tail with an anchor sequence (downstream primer). The product was cloned into pUC18 and sequenced. A reading frame of 648 bases in the sequence encoded a protein which has 30% homology with the alpha family of mammalian glutathione S transferases. PMID- 7883438 TI - The Indian soft-furred rat, Millardia meltada, a new host for Nippostrongylus brasiliensis, showing androgen-dependent sex difference in intestinal mucosal defence. AB - Susceptibility of the Indian soft-furred rat, Millardia meltada, to infection with the intestinal helminth, Nippostrongylus brasiliensis, was examined. After subcutaneous infection with 1500 infective larvae (L3), daily faecal egg output (EPG) of both male and female animals reached a peak at 1 week post-infection (p.i.) with the same magnitude (about 20,000 epg faeces) and then rapidly decreased below detection level at around 2 weeks p.i. In male animals, however, after a transient cessation at 2 weeks p.i., parasite eggs reappeared in faeces 3 weeks afterwards, though the counts were far lower than the first peak. This phenomenon was rarely seen in female animals. High susceptibility of M. meltada to N. brasiliensis was confirmed by worm burdens. About 70% of the initial dose of larvae became adult worms in the intestine of male and female hosts. As suggested by the decline in egg counts, the majority of adult worms were expelled by 2 weeks p.i. The residual worm burden at 2 and 4 weeks p.i. was significantly higher in male than female animals. When orchidectomized males were infected with N. brasiliensis, the magnitude of residual worm burden was significantly reduced. On the other hand, ovariectomy did not affect the number of residual worms in females. PMID- 7883440 TI - Isolation and biochemical characterisation of a glutathione S-transferase from Echinococcus granulosus protoscoleces. AB - A protein fraction migrating as a M(r) 24 kDa band on SDS-PAGE was isolated by affinity chromatography on glutathione-agarose from a soluble extract of E. granulosus proto-scoleces from sheep(UK). This fraction had glutathione S transferase activity of 0.4 mumol min-1 mg-1 when measured using a standard synthetic substrate and its determined N-terminal amino acid sequence most closely resembled Mu class glutathione S-transferases. In addition, protoscoleces from the distinct sheep and horse E. granulosus strains showed a different pattern of glutathione-binding proteins: the M(r) 24 kDa species was obtained in both cases whereas an additional band of slightly faster electrophoretic mobility was isolated from horse(UK) protoscoleces. PMID- 7883441 TI - Comments on Poulin, R. the disparity between observed and uniform distributions: a new look at parasite aggregation. PMID- 7883442 TI - Antibody responses of sheep to challenge with Trichostrongylus colubriformis and the effect of dexamethasone treatment. AB - Eight-month-old random bred Romney wether lambs were reared nematode-free in pens and assigned to 4 groups each of 5 lambs. Lambs in 3 groups were infected orally, twice a week, with 5000 Trichostrongylus colubriformis infective larvae (L3), a control group remained unifected throughout. Two infected groups were treated with dexamethasone (0.5 mg kg-1 bodyweight), one between days -7 and 77, the other between days 77-154. Nematode challenge infection was withheld from the third group from day 133 after anthelmintic treatment. Nematode eggs in sheep faeces (FEC) were monitored at weekly intervals. T. colubriformis-specific antibody levels were determined twice a week and specific immunoglobulin isotypes (IgA, IgG1, IgG2 and IgM) determined weekly in serum samples using ELISA. Resistance, as measured by FEC, was expressed by 35 days after L3 infection began but sheep dosed with dexamethasone did not develop resistance. Extant resistance was abrogated in sheep dosed with dexamethasone. Nematode challenge resulted in elevated serum levels of antibodies to T. colubriformis L3 excretory/secretory antigens, these consisted predominantly of IgG1 and IgM. The IgG1 response was more persistent than the IgM response. Specific serum IgA and IgG2 responses were low, but significant, in nematode-challenge sheep. Dexamethasone treatment prevented the antibody responses and resulted in a rapid reduction of extant antibody levels in resistant sheep. Weight gain was reduced by nematode challenge with or without dexamethasone treatment compared with control sheep. PMID- 7883443 TI - Echinococcus granulosus: the mechanism of oncosphere lysis by sheep complement and antibody. AB - A heat-labile component of normal sheep serum (56 degrees C for 30 min but not 50 degrees C for 30 min) was able to lyse oncospheres in vitro. The degree of effect, and the proportion of oncospheres lysed, was related to the concentration of normal unheated sheep serum complement, or other sources of complement (rabbit, mouse) in the culture. Lower concentrations were required for lysis if the culture serum was obtained from sheep immune to E. granulosus infection. Heat inactivation of normal or immune sheep serum removed any lytic ability. No lysis occurred in any concentration of unheated foetal lamb serum. However, unheated foetal lamb serum was able to restore the lytic effect to heated normal or immune serum. This suggests that lysis in both immune and normal serum is antibody dependent and complement-mediated. The lysis in normal serum would appear to be due to natural cross-reacting antibodies that can fix complement at the oncosphere surface. The complement lesion resulted in damage to the plasma membrane. This then peeled back, predisposing the oncosphere to osmotic destruction. The use of bleach to dissolve the embryophore caused damage to the plasma membrane similar to that caused by complement. Developing metacestodes at 3 days of age in vitro in immune serum were susceptible to the addition of complement at that time. PMID- 7883444 TI - Use of specific antibody and circulating antigen serum levels in the hydatid immunodiagnosis of asymptomatic population. AB - Levels of specific antibodies (Ab) and circulating antigens (CAg) were tested by ELISA in sera from 115 surgically confirmed hydatid patients, 41 individuals exhibiting other parasitic and unrelated diseases and 69 healthy subjects. Addition of CAg data to Ab detection in this sera collection increased sensitivity from 85% (only Ab) to 89% (Ab + CAg). Combination of ultrasonography with Ab and CAg serology for diagnosis of asymptomatic population in endemic areas was analyzed. One field survey (163 persons) involved both blood extraction and ultrasonography to all the population. Three people exhibited cyst images and all of them were Ab positive, while 6 Ab and 1 CAg positive individuals exhibited no cyst image. Another survey (1620 persons) involved a selection of 85 subjects for serology according to ultrasound data and record of family hydatid history. Twelve per cent exhibited no hydatid image being serologically positive and 14% were serologically negative but exhibited cyst image. Ultrasonography and serology (Ab and CAg) should be used in combination to maximize the diagnostic yield in asymptomatic population. PMID- 7883445 TI - Identification of Schistosoma mansoni antigens recognized by spleen cells of C57B1/6 mice immunized with ultraviolet-irradiated cercariae. AB - Spleen cells of C57B1/6 mice immunized twice with Schistosoma mansoni cercariae attenuated by ultraviolet irradiation proliferated and produced interleukin-(II) 2 and/or II-4 in response to both soluble schistosomular and adult worm antigens of 72-68, 60-62, 50, 45, 29.5 and 28 kDa. All of these bands, except the 45 kDa, were also recognized by serum antibodies in Western blotting. PMID- 7883446 TI - Regulatory effect of anti-interleukin-5 monoclonal antibody on intestinal worm burden in a primary infection with strongyloides venezuelensis in mice. AB - The intestinal worm burden in Strongyloides venezuelensis-infected mice was influenced by treatment with anti-interleukin-5 (IL-5) monoclonal antibody (NC17) when NC17 was given to mice 3-7 days before infection. The present study has examined the involvement of IL-5 in susceptibility at different in the development of the parasite in the host. The results show that the number of tissue-migrating larvae recovered from the lungs in a primary infection was not affected by anti-IL-5 monoclonal antibody treatment, whereas intestinal worm counts increased in mice treated with 0.25-1 mg of NC17. In mice treated with 0.1 mg of NC17, adult worm recovery was not significantly different from non-treated controls. Peripheral and tissue eosinophilia were not observed in the early phase of infection (days 4-8). Six days after transfer of lung-stage larvae to NC17 treated mice, adult worm recovery was higher than that of control mice. These results suggest that non-eosinophil response(s), which were dependent on IL-5, were involved in the initial establishment of the intestinal stage of S. venezuelensis in mice. We discuss the mechanisms that control the susceptibility to the parasite from the viewpoint of host defence. PMID- 7883447 TI - Nippostrongylus brasiliensis: ability of plasma to prime free radical generation by leukocytes in response to adult worms not due to gamma-interferon or tumour necrosis factor. AB - Plasma-borne factors prime leukocytes from both infected and uninfected rats for radical generation in response to N. brasiliensis. The concentration of these factors is increased following infection and reaches maximal levels on day 8 post infection (p.i.) as demonstrated by the striking ability of plasma from infected rats to prime leukocytes from uninfected rats to produce free radicals in response to adult worms. The cytokines, gamma-interferon and tumour necrosis factor (TNF) can be detected in plasma during infection with a variety of organisms and several lines of immunological and pathophysiological evidence, including radical generation, weight loss, anaemia and diarrhoea, implicate generation of these proteins in response to infection with N. brasiliensis. We therefore investigated whether gamma-interferon and TNF were detectable in the plasma of rats infected with N. brasiliensis and whether the presence of these cytokines correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis. However, gamma-interferon was not detected in the plasma of rats at any time after infection with N. brasiliensis and neutralizing monoclonal antibody to rat gamma-interferon had no effect on the ability of plasma to prime free radical generation. TNF was detected in the plasma of heavily-infected rats but only at very low levels (< 1 ng/ml), though copius in vivo synthesis of TNF could be induced by treatment of the infected rats with lipopolysaccharide (LPS). However, neither parasite-induced nor parasite plus LPS induced plasma TNF correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883448 TI - Identification and partial characterization of the proteases from different developmental stages of Schistocephalus solidus (Cestoda: Pseudophyllidae). AB - The proteolytic activities of extracts prepared from procercoids and plerocercoids as well as adults of the pseudophyllidean cestode Schistocephalus solidus were examined using several proteins and synthetic peptides as substrates. Whole bodies of procercoids and the isolated syncytial tegument of plerocercoids and adults prepared by freeze-thaw were studied. Extracts of procercoids contained a chymotrypsin-like proteinase exhibiting a molecular weight of 23,500 determined by gel filtration chromatography. The proteinase showed collagenolytic activity and had a pH optimum at 8. Such a proteinase was absent in plerocercoids and adults. In these developmental stages leucine aminopeptidases were detected in the isolated syncytial tegument having molecular weights of 93,500 (plerocercoids) and 89,000 (adults), respectively. The aminopeptidases in both stages displayed optimal activity at pH 8.5. The chymotrypsin-like proteinase of the procercoid is possibly necessary for the penetration of the host's intestinal wall, whereas the aminopeptidases of the plerocercoid and the adult of S. solidus may aid in parasite nutrition by degrading oligopeptides at the tegumental surface. PMID- 7883449 TI - The chemosensitivity of the rodent malarias--relationships with the biology of merozoites. AB - According to the hypothesis proposed by Landau, Cambie & Chabaud (1990, Annalees de Parasitologie Humaine et Comparee 65: 101-103), the chemoresistance of malaria is related to the selection of strains with latent merozoites, the latter being capable of penetrating into red blood cells at other times than that of the time of schizogony and reinfect the host with as much of a delay as several days. They determine an asynchronism of the schizogonic rhythm and, being so far resistant to all known medication, should induce, at least to some extent, a chemoresistance. Consequently, there are three factors linked to merozoites: latency, asynchronism and chemoresistance. The relationship between asynchronism and latency of merozoites has been demonstrated previously (Cambie, Landau & Chabaud, 1990, Compte Rendus de l'Academie des Sciences de Paris 310: 183-188.). In the present work it was shown that the two classifications of strains, first in order of increasing chloroquine resistance, second in order of increasing degree of persistance of merozoites in the blood, are almost identical for the 10 strains, subspecies or species of Plasmodium considered. The relationship between latency of merozoites and chemoresistance appears to have been demonstrated. PMID- 7883450 TI - Pathology of infection with Paramphistomum ichikawai in sheep. AB - Lambs were given 40,000 or 50,000 metacercariae of Paramphistomum ichikawai by injection into the rumen and necropsied at 21, 42 and 84 days after infection. Pathological changes were observed grossly and confirmed histologically in the small intestine and rumen. The numbers of flukes and their location in the gastrointestinal tract were recorded and the populations of eosinophils, mast cells and globule leucocytes estimated. Changes varied, according to the numbers of flukes present, from a localised enteritis and villous atrophy in the duodenum in light infections to severe destruction of the mucosa extending into most of the jejunum in heavy infections. As the infection progressed changes were characterised by extensive thickening and fibroplasia in the mucosa and submucosa. Severe damage to the mucosa of the rumen was also observed in heavy infections. Heavy infections were associated with increased infiltration with eosinophils. Mast cells were generally depleted and globule leucocytes only appeared after the flukes had left the small intestine. Migration of the flukes from the small intestine was delayed in heavy infections exacerbating the effect of the infection. It is suggested that the presence of 20,000 to 25,000 flukes would result in clinical disease; smaller numbers would cause significant subclinical disease. PMID- 7883451 TI - Effects of prefrontal cortex lesions on visual evoked potential augmenting/reducing. AB - Visual evoked potentials to 4 stimulus intensities were recorded from Fz, Cz, and Oz, all referred to A2, in 23 neurologically normal subjects and 21 neurosurgical patients with prefrontal lesions. The response amplitude as a function of intensity was evaluated for P1/N1 and N1/P2 components. At the Oz lead, the EP amplitude consistently increased with brighter stimuli more rapidly in the prefrontal group than in the controls. Similar, though less consistent, effects were seen at Fz and Cz. These findings suggest that the phenomenon of augmenting/reducing is at least partially influenced by prefrontal-mediated inhibition of sensory processes. PMID- 7883452 TI - Mental practice of motor skills used in poststroke rehabilitation has own effects on central nervous activation. AB - In the last years it has been shown that the use of the EMG triggered electrical myostimulation (ETEM) brings good results in poststroke rehabilitation. It has been hypothesized that the relearning effects obtained by means of ETEM are due to the reinstatement of proprioceptive feedback. However, the technique is most powerful if imagination of motor acts (the so called mental practice) is used as an initial part of ETEM. Since mental practice in healthy people leads to central nervous activation processes as well as to an improvement of motor skills, we investigated the effects of mental practice alone on central nervous activity by means of EEG in stroke patients. Twelve left-sided hemiplegic patients who underwent a specific poststroke rehabilitation treatment were requested to perform a simple arm movement sequence. In the following mental practice period the patients were requested to imagine the same sequence without any real movement. EEG background activity was recorded during baseline and imagination periods. After the calculation of z-transformed power values within the alpha and beta-1 band, differences between rest and imagination periods were evaluated for significance. Stroke patients showed significant decreases of alpha as well as beta-1 power during mental practice in comparison to the rest period. These changes are similar to those obtained in healthy subjects. Central alpha power diminished only during imagination of the contralateral arm. This phenomenon as well as the decrease of beta-1 power in central derivation were also obtained during real motor performance and might indicate an activation of the sensorimotor cortex. In accordance with the hypothesis of internal feedback mechanisms, this activation is a necessary prerequisite for motor learning during mental practice. We conclude that mental practice of motor skills might have own effects in poststroke rehabilitation. PMID- 7883453 TI - Special talents in Geschwind's and Galaburda's theory of cerebral lateralization: an examination in a female population. AB - Geschwind and Galaburda (1985) proposed that delayed growth of posterior left hemisphere sites in male dyslexics are associated with markers of anomalous dominance (AD) and special cognitive talents. We found that talent in a female population was related to the strength of nonright-handedness, and was elevated in right-handed individuals with histories of familial left-handedness. Subjects reporting a history of dyslexia tended to be musically talented. While immune disorders were not related to talent for the whole population, they did co-occur with talents in a group of 10 individuals reporting 7 or more AD markers. PMID- 7883454 TI - Spatial acalculia. AB - Twenty-one patients with right hemisphere damage were studied (11 men, 10 women; average age = 41.33; range 19-65). Patients were divided into two groups: pre Rolandic (six patients) and retro-Rolandic (15 patients) right hemisphere damage. A special calculation test was given. Different types of calculation errors were analyzed. Spatial alexia and agraphia for numbers, loss of calculation automatisms, reasoning errors, and general spatial defects interfering with normal number writing and reading, were observed. Number processing was impaired, whereas the calculation system was partially preserved. Fact retrieval and procedural difficulties were observed, but arithmetical rules were properly used. It is concluded that calculation abilities in right hemisphere damaged patients are disrupted as a result of: (1) visuospatial defects that interfere with the spatial arrangement of numbers and the mechanical aspects of mathematical operations: (2) inability to recall mathematical facts and appropriately to use them; and (3) inability to normally conceptualize quantities and process numbers. PMID- 7883455 TI - Effect of selenium and vitamin E on iminodipropionitrile induced dyskinesia in rats. AB - The present study was undertaken to determine the effect of combination of selenium and vitamin E on experimentally induced dyskinesia in rats. The dyskinetic syndrome was produced in 4 groups of 6 male rats each weighing 250 300g by intraperitoneal (ip) administration of iminodipropionitrile (IDPN) in doses of 100 mg/kg body weight daily for 12 days. A group of 6 rats (group 1) served as control and received normal saline only. The rats in group 2 (IDPN only) received normal saline (ip) 30 minutes before the administration of IDPN. The animals in groups 3, 4 and 5 received selenous acid (5 mumol/kg), vitamin E (500 mg/kg p.o.) and a combination of selenous acid and vitamin E respectively, daily, 30 minutes before IDPN for 12 days. Twenty four hours after the last dose of IDPN, the dyskinetic behavior including vertical head movements (retrocollis), horizontal head movements (laterocollis), circling and backwalking of each rat was studied for a period of 10 minutes. Immediately after behavioral studies, the animals were sacrificed and brains were dissected out for the analysis of conjugated dienes, lipid hydroperoxides and vitamin E. The results of this study showed that treatment of rats with IDPN only for 12 days produced dyskinetic syndrome in all the rats characterized by vertical and horizontal head movements, circling and backwalking. Concomitant treatment of rats with vitamin E and selenium individually reduced IDPN induced dyskinesia, and the symptoms were almost completely absent when the combination of these two agents was used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883456 TI - Endogenous opioid peptide level changes under electrostimulation and their assessment by the EEG. AB - Endogenous opioid peptide (EOP) system plays an important role in the interaction of human organism with different stress factors, providing stress-limiting and stress-protective functions. Different kinds of electrostimulation seem to produce anti-stress and pain relief effects due to EOP system activation. The presented paper reviews recent literature concerning EOP system activation under electrostimulation and its reflections in the EEG characteristics. The results and opportunities of high resolution EEG structure analysis utilization for EOP level control, as well as for stress-induced state assessment and correction via resonance activation of brain EEG oscillators by means of frequency-tuned external stimulation are presented. PMID- 7883457 TI - Are frontal and parietal somatosensory evoked potentials functionally dissociated by changing stimulus rate? AB - The cortical somatosensory evoked potentials are known to be sensitive to relatively small changes in the stimulus repetition rate of the afferent nerve. However, conflicting reports exist as to whether frontally and parietally recorded potentials at a given latency show differential behaviors as a function of stimulus rate. Because such dissociations of frontal and parietal potentials can have significant implications for the SEP generation mechanisms, the present study was undertaken to further describe in detail these effects on frontal, central and parietal waveforms after median nerve stimulation. Increasing stimulus repetition rate from 1 Hz to 5 Hz had the following effects: (i) in 9 of 16 subjects, the frontal P20 diminished while parietal N20 clearly remained unaltered, (ii) the central P22 was reduced in all subjects, (iii) frontal N30 and parietal P27 were attenuated in all subjects, the average magnitude of the reductions being nearly equal for these deflections. The results support the view that changing stimulus rate can functionally dissociate frontal and parietal activity around 20 ms, indicating that several partially independent neural populations can contribute to the frontal P20. The results did not lend support for functional dissociation of frontal N30 from parietal P27. PMID- 7883458 TI - Modulation of the electrically evoked blink reflex by different levels of tonic preinnervation of the orbicularis oculi muscle. AB - Eleven subjects were instructed to maintain different levels of tonic pre innervation of the two orbicularis oculi muscles: relaxation, 25%, 50%, 75% and 100% of maximum voluntary contraction. Surface electromyographic activity was recorded unilaterally from the left orbicularis oculi muscle while cutaneous reflex responses were evoked electrically during different levels of pre innervation. Latencies of the early (R1) and late (R2) blink reflex responses were significantly shorter during moderate pre-innervation level (25%) compared to relaxation, with no further latency decrease under stronger tonic pre innervation. The amplitude of the R1 component increased significantly until a pre-innervation level of 50% of maximum voluntary contraction was reached. There was no further amplitude enhancement with stronger pre-innervation. R2 amplitudes linearly increased with the increasing pre-innervation levels, possibly reflecting recruitment of a greater number of motor units for the late component or a postponement of motoneuron synchronization of the late component. PMID- 7883459 TI - P3 event-related potentials and performance of young and old subjects for music perception tasks. AB - Event-related potentials and performance data were recorded from young and old subjects performing six tasks involving auditory discrimination of musical stimuli. Tasks included pure tone, timbre, rhythm, and interval discrimination, detection of a meter shift, and discrimination of open and closed harmonic endings for chord progressions. P3 latencies were generally longer for the old subjects. P3 amplitude and performance differences between subject groups were not significant. Our results provide a quantitative probe of the neural and behavioral significance of the influence of aging and stimulus complexity on the processing of some of the elementary constituents of music. In particular, pure tone and timbre discrimination appear to correspond to behaviorally and neurally simpler processing than does discrimination of the other musical constituents tested in our study. PMID- 7883460 TI - Effect of vitamin E on chromosomal damage in bone marrow cells of mice having received low dose of X-ray irradiation. AB - When mice had received various doses (0, 0.1, 0.2, 0.4 and 0.8 Gy) of X-ray to their whole bodies, the increased % of reticulocytes with micronucleus (MNs) in peripheral blood, an indicator of chromosomal damage in bone marrow cells, was the highest at 44 hr after the irradiation. At the time, the dose-dependent increase of the % was clearly observed. Using this method, the protective effect of vitamin E on X-ray-induced chromosomal damage was examined. Mice were given various doses (0, 75, 300 mg/kg body weight) of vitamin E by intragastric gavage for 4 days, or fed either a basal vitamin E diet (3 mg % of vitamin E) or a high vitamin E diet (100 mg % of vitamin E) for 5 weeks. Then, the mice were given whole body X-ray irradiation at the dose of 0.3 or 0.4 Gy. Vitamin E concentration in bone marrow cells was significantly elevated by the vitamin E treatment, but was not decreased after irradiation. The vitamin E treatment was unable to inhibit the % of reticulocytes with MNs induced by the irradiation. These results indicate that vitamin E in the bone marrow could not significantly prevent chromosomal damage in bone marrow cells against a low dose of X-ray irradiation. PMID- 7883461 TI - Riboflavin sensitized photooxidation of tyrosine. AB - The oxygen reactive species generated during the photooxidation of tyrosine sensitized by riboflavin were studied and the products formed were isolated. It was found that this process occurs preferently through a type I mechanism, which involves the direct interaction between the excited state of the sensitizer and tyrosine. The formation of O2.-, H2O2 and .OH was detected along the photooxidative process. By changing H2O by D2O it could be established that 1O2 has no significant role in the photooxidation of tyrosine sensitized by riboflavin. When a previously irradiated solution of tyrosine was applied to a Sephadex G-15 column, four fractions could be separated corresponding to products having hydrodynamic volumes larger than those of the reactants. By the use of 14C tyrosine the aminoacidic origin of the products could be determined; one of them was identified as bityrosine, according to its fluorescence properties and 1H-NMR spectrum. PMID- 7883462 TI - Optimal and stable conditions for the determination of erythrocyte glutathione reductase activation coefficient to evaluate riboflavin status. AB - To measure the activation coefficient (AC) of erythrocyte glutathione reductase (GR), suspended whole blood was lysed in a preincubation solution, with or without 100 microM flavin adenine dinucleotide (FAD). Upon addition of the reaction mixture, FAD concentration decreased about 10-fold. No AC values < 1 were obtained in any of the subjects. The range of unstimulated activity per g hemoglobin (Hb) was 5 to 12 U. AC values of healthy subjects (1.3) decreased to about 1.15 after vitamin supplementation of 1 RDA for 3 wk. In healthy young subjects consumption of dietary riboflavin at levels as low as 0.5 mg/d resulted in an AC of 1.6. PMID- 7883463 TI - Interaction among dietary vitamin B6, proteins and lipids: effects on liver lipids in rats. AB - Vitamin B6 is involved in protein and lipid metabolism. Yet the effect of pyridoxine deficiency has been studied in relation to separate dietary parameters, we aim to investigate the effect of pyridoxine deficiency associated with a high intake of proteins and/or low EFA content in the diet. Vitamin B6 and PLP contents, fatty acid compositions of lipids and phospholipids were determined in liver of groups of rats fed on diets with different amounts of proteins (20 40%) and EFA (2-35%). The results show a complex interaction among tested nutritional factors with a prevailing influence of dietary proteins on lipid content of liver and of low EFA intake and vitamin B6 on PUFA metabolism. The effects of pyridoxine deficiency on lipid metabolism were dependent on the EFA content of the diet. PMID- 7883464 TI - Cobalt-vitamin B12 deficiency causes lipid accumulation, lipid peroxidation and decreased alpha-tocopherol concentrations in the liver of sheep. AB - A disease, known as ovine white liver disease (OWLD) was experimentally reproduced in lambs by feeding a diet depleted of cobalt. At necropsy, affected animals had pale, swollen, friable fatty livers, and showed marked accumulation of lipofuscin. Control animals, fed the same diet to which adequate amounts of cobalt had been added, were clinically normal. In animals with OWLD, liver triglyceride and free fatty acid concentrations were increased. A decrease in the ratio of phosphatidyl choline to phosphatidyl ethanolamine in the liver may result in a reduced ability to export triglycerides as very low density lipoprotein. This may cause the lipid accumulation characteristic of OWLD. Lipofuscin accumulation, another feature of OWLD, is a consequence of lipid peroxidation. Evidence for a peroxidative challenge was provided by the finding of reduced concentrations of alpha-tocopherol, elevated concentrations of induced 4-hydroxynonenal, and decreased amounts of the most readily peroxidizable fatty acids in the liver of animals with OWLD, by comparison with controls. The initiator of the peroxidative challenge is unknown, but may be related to the finding of increased concentrations of homocysteine in the plasma of animals with OWLD. PMID- 7883465 TI - Ascorbate and exercise in the Northern Ireland population. AB - The relationship between physical activity, physical fitness and serum ascorbate was examined in the Northern Ireland Health and Activity Survey. This was a cross sectional population study (n = 1600), using a two stage probability sample, of the population of N. Ireland. Physical activity profile was recorded by computer assisted interview and physical fitness was determined by estimation of VO2 max by extrapolation from submaximal oxygen uptake. Serum ascorbate was measured using a colorimetric reaction of 2,4 dinitrophenylhydrazine with dehydroascorbate. Mean serum ascorbate was greater in females than males (p < 0.001), and was lower in smokers than non-smokers in both males (p = 0.01) and females (p < 0.001). There was no statistically significant relationship between serum ascorbate and age, social class, body mass index, physical activity or physical fitness in males but there was a relationship with age (p < 0.01) and physical fitness (p < 0.05) in females. PMID- 7883466 TI - Plasma vitamin C assays: a European experience. EC FLAIR Concerted Action No. 10: Micronutrient Measurement, Absorption and Status. AB - Assay procedures for plasma concentrations of vitamin C, and hence for vitamin C status, currently in use in European population-surveillance laboratories and elsewhere, are based on a wide range of disparate techniques and reactions. The problem of achieving harmonisation between these techniques, and between laboratories, is further complicated by the instability of the vitamin, and the existence of several chemical forms. In the course of a European Community FLAIR programme, of inter-laboratory assay method comparisons for micronutrients, nine European laboratories performed either one or two coordinated ring tests, and some coordinated checks on in-house plasma samples, spiked with a low level of ascorbic acid. The principal conclusion was that good agreement was difficult to obtain, between laboratories and between methods, at plasma vitamin C concentrations close to the cut-off for biochemical deficiency, i.e. ca. 11 microM vitamin C in untreated plasma. By the second ring test, and after the correction of some aberrant results due to malfunctioning apparatus, interlaboratory coefficients of variation of 13-20% were achieved, within the biochemically "normal" range of 36-94 microM. There remains, however, a need for critical within and between-laboratory checks and comparisons, and for new quality control materials, with assigned values. PMID- 7883467 TI - FLAIR intercomparisons on serum and red cell folate. AB - Interlaboratory variation in the results for serum and red cell folate was assessed as part of the EC FLAIR Concerted Action No 10 with 11 participating laboratories from 7 European countries. In the first intercomparison freeze dried quality control serum samples at two different levels were analysed using different assay methodologies (microbiological, radioassay, HPLC and chemilumiscence). Considerable variability was observed both between different methods ("over-all" coefficient of variation (CV) 18-41%), as well as between laboratories using a similar assay kit/protocol. In the second intercomparison recovery studies were performed with sera spiked with calibrated standard preparations of pteroylmonoglutamic acid (PGA) or 5-methyltetrahydrofolic acid (5 MTHF). With radioassays average PGA recoveries ranged between 86-140% (mean 110%), for 5-MTHF between 99-144% (mean: 130%). In the third intercomparison with commercial whole blood control samples variabilities (CV's) between 36 and 63% were found. These results indicate that especially radioassays tend to overestimate serum folate content due to improper standard calibration. Also small differences in assay pH as well as matrix effects may contribute to the variability. These data stress the importance of improved standardization of (commercial) diagnostic kits and the provision of suitable reference materials with assigned folate levels spanning its physiological concentration range. PMID- 7883468 TI - Effects of ageing on folate metabolism in rats fed a long-term folate deficient diet. AB - The present study was focused on the effects of feeding to young (2 mo. old) and aged (30 mo. old) rats either a folate repleted or a folate deficient diet for seven weeks on several markers of folate metabolism. Serum and liver folate contents were determined, and hepatic distribution of folates based on glutamic acid chain length and pteridine ring was obtained. In addition, liver s adenosylmethionine (Ado Met) and s-adenosylhomocysteine (AdoHcy) concentrations, as well as serum homocysteine concentration have been also determined. Ageing itself seems not to be associated with lower hepatic folate content, but in serum a 50% decrease was observed. Feeding the folate deficient diet did result in significant lower (p < 0.001) liver folate content in both age groups, and in marked decreases in serum folates. These quantitative changes in the folate deficient groups were associated with an elongation of the glutamate chain length, mostly represented by a significant decrease in the proportion of pentaglutamyl derivatives, an increase of hexaglutamyl, and appearance of hepta and octaglutamyl folate derivatives. However, there were no important modifications in the pteridine ring distribution regardless of the age and level of dietary folate. In the present study, ageing seems to be associated with a significantly lower AdoMet/AdoHc ratio (65% decrease, p < 0.05), irrespective of the folic acid included in the diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883469 TI - Diet intake and vitamin supplement use of Hungarian women during the preconceptional period. AB - The Hungarian participation in the establishment of the new primary prevention of neural-tube defects by periconceptional supplementation with multivitamins including folic acid or with folic acid alone has been significant. Food and supplement consumption during the preconceptional period are hypothesized to closely reflect intakes during the time of neural-tube development, i.e., between the 15th and 28th day postconception. A daily personal diary of food intake during one month of the preconceptional period was evaluated and the data on vitamin supplement use were obtained by interview. In Hungary, folic acid (158.5 micrograms/day) in the normal diet does not seem to be sufficient to reduce the risk of neural-tube defects. The women who used multivitamin supplements routinely in the preconceptional period were not attempting to prevent neural tube defects as no women took single folic acid supplement in the study. PMID- 7883470 TI - Antioxidant vitamins in malnourished Nigerian children. AB - The antioxidant capacity in malnutrition--as far as it is related to vitamins- was studied by determining the plasma concentrations of the most prominent antioxidant vitamins (retinol, tocopherols, carotenoids, cryptoxanthine, lycopene, and ubiquinone-10) in marasmic (M; n = 15), severe marasmic (SM; n = 8), kwashiorkor (KW; n = 12), and normally nourished (CO; n = 18) children in Nigeria. Retinol was found to be reduced in severe marasmic children when compared to local controls (medians and interquartile ranges; SM: 155 micrograms/l, 117-178 micrograms/l; CO: 281 micrograms/l 209-413 micrograms/l; p < 0.005). A strong correlation between plasma retinol and retinol binding protein could be found in all groups (SM: r = 0.79; M: r = 0.93; KW: r = 0.80; CO: r = 0.70). The tocopherol/lipid-ratio was lowered in kwashiorkor (median 0.48 mg/g, interquartile range 0.41-0.66 mg/g). A sufficient tocopherol status was only found in one child with kwashiorkor. alpha-Carotene, beta-carotene, cryptoxanthine and lycopene were below the detection limits in most of the malnourished children. Plasma ubiquinone-10 was significantly higher in kwashiorkor (median 1.05 micrograms/ml, interquartile range 0.88-1.17 micrograms/ml) than in all other groups (CO: 0.71 micrograms/ml, 0.55-0.99 micrograms/ml: M: 0.72 micrograms/ml, 0.65-0.83 micrograms/ml; SM: 0.89 micrograms/ml, 0.61-0.83 micrograms/ml). It is concluded that a depletion of antioxidant vitamins is present in malnourished Nigerian children, especially pronounced in the kwashiorkor syndrome. The mechanisms leading to elevated plasma ubiquinone-10 in kwashiorkor require further studies. PMID- 7883471 TI - Antioxidative effect of dietary coenzyme Q10 in human blood plasma. AB - The effect of an oral dose of 90 mg/day coenzyme Q10 on the antioxidative status in 22 healthy young subjects (9 men and 13 women) was investigated before and after induction of an oxidative stress by fish oil supplementation. The levels of oxidised and reduced coenzyme Q10, alpha-tocopherol, ascorbate, TBARS and the fatty acid composition of phospholipids were determined in plasma. The total amount of plasma coenzyme Q10 increased significantly from 0.7 +/- 0.1 mumol/l before supplementation to 1.7 +/- 0.3 mumol/l after one week of supplementation while the redox status (reduced CoQ10/total CoQ10) remained constant, even during a following fish oil supplementation. The level of TBARS decreased during the first 2 weeks of CoQ10 ingestion while the content of alpha-tocopherol increased in the second week and ascorbate did not change. The decrease of TBARS and the presence of the majority of the orally supplemented CoQ10 in the reduced form in plasma seem to indicate an antioxidative role of CoQ10 in blood plasma. PMID- 7883472 TI - Effects of fructooligosaccharides on the absorption of magnesium and calcium by cecectomized rats. AB - We reported previously that feeding of fructooligosaccharides (FO) increased the apparent absorption of calcium (Ca), magnesium (Mg) and phosphorus (P) in rats. We suggested that there was an important correlation between this phenomenon and fermentation of FO in the large intestine. However, the precise mechanism remained to be characterized. Therefore, we performed a mineral-balance study to identify the segment of lumen in which FO affects mineral absorption, using cecectomized rats. Sham-operated rats and cecectomized rats were fed a control diet (without FO) or an FO-diet (containing 50 g of FO per kg of feed) for 28 days. Feeding of the FO-diet decreased the luminal pH in the cecum and colon in the sham-operated rats. In the cecectomized rats, feeding of the FO-diet also decreased the luminal pH in the colon. Thus, FO was fermented in the colon of the cecectomized rats. However, the acid composition of feces was altered by cecectomy. Feeding of the FO-diet increased the absorption of Ca and Mg in the sham-operated rats. In the cecectomized rats, the FO-diet increased the absorption of Mg but did not increase the absorption of Ca. These results suggest the mechanisms for the absorption of Ca and Mg when rats are fed an FO are different. PMID- 7883473 TI - Iron status, blood lipids and endogenous antioxidants in response to dietary iron levels in male and female rats. AB - The effect of dietary iron levels on iron status, blood lipids and endogenous antioxidants was investigated in male and female rats. Diets low in iron (15 mg/kg Fe; LFe) or high in iron (400 mg/kg Fe; HFe) were given to groups of male (n = 6) and female (n = 6) weanling rats for six weeks. In a second experiment the same dietary iron levels were fed to groups (n = 12) of males and females for seven months, during which colon tumours were induced. Indices of iron status, blood lipid levels and antioxidant enzyme activities were measured in both experiments. In the first experiment, indices of iron status were significantly higher in HFe rats and in females compared with males. Cholesterol and triglycerides were significantly higher in HFe rats and cholesterol was significantly higher in males. Plasma albumin and bilirubin levels and plasma caeruloplasmin activity were significantly higher in female rats. The second experiment confirmed the higher indices of iron status in HFe rats and in female rats, and also showed that plasma cholesterol levels were significantly higher in HFe rats. There were no consistent, significant differences over both experiments in activities of the antioxidant enzymes measured. Results show that higher dietary iron levels are associated with higher cholesterol levels in male and female rats. However cholesterol was found to be higher in male rats while iron status was higher in female rats. This indicates that factors other than iron status are responsible for the differences in cholesterol in male and female rats. PMID- 7883474 TI - Influence of dietary fat components and intestinal resection on iron, zinc and copper metabolism in rats. AB - The effect of resecting 50% of the distal small intestine (DSI) on iron, zinc and copper nutritive utilization was studied in rats fed two different types of diet: a standard diet containing 4% olive oil (A) and a diet containing different sources of fat (1/3 olive oil, 1/3 sunflower oil and 1/3 medium chain triglycerides) (B). One month and 7 days after surgery, intestinal resection led to a deterioration in digestive (ADC) and metabolic (balance) utilization of iron, zinc and copper. To assess trace metal postresectional homeostasis, we also measured these mineral concentrations in whole blood, plasma and several organs (liver, femur, sternum, longissimus dorsi muscle and testes). Our findings showed no significant differences in iron, zinc and copper concentrations between the organs, suggesting that the observed decrease in digestive and metabolic efficiency of these minerals was not markedly reflected at the postabsorptive level, since the distribution of the trace elements in the whole organism remained unchanged. We conclude that one month and 7 days after this surgical intervention, adaptive mechanisms are well developed in resected rats fed a diet with an adequate mineral supplement. PMID- 7883476 TI - Reentry and the problem of cortical integration. PMID- 7883475 TI - Population activity in the control of movement. PMID- 7883477 TI - Coherence as an organizing principle of cortical functions. PMID- 7883478 TI - Temporal mechanisms in perception. PMID- 7883479 TI - Selection versus instruction: use of computer models to compare brain theories. PMID- 7883480 TI - Memory and forgetting: long-term and gradual changes in memory storage. PMID- 7883481 TI - Population thinking and neuronal selection: metaphors or concepts? PMID- 7883482 TI - Implicit knowledge: new perspectives on unconscious processes. PMID- 7883483 TI - Phantom limbs, neglect syndromes, repressed memories, and Freudian psychology. PMID- 7883484 TI - Selectionist and instructionist ideas in neuroscience. PMID- 7883485 TI - Neural darwinism and a conceptual crisis in psychoanalysis. PMID- 7883486 TI - A new vision of the mind. PMID- 7883487 TI - Morphoregulatory molecules and selectional dynamics during development. PMID- 7883488 TI - Exploration and selection in the early acquisition of skill. PMID- 7883489 TI - Laparoscopic surgery comes of age. PMID- 7883490 TI - The evolving role of ERCP and laparoscopic common bile duct exploration in the era of laparoscopic cholecystectomy. PMID- 7883491 TI - Laparoscopic cholecystectomy: cost effectiveness and quality enhancement. PMID- 7883492 TI - Laparoscopic cholecystectomy in 1000 consecutive cases. PMID- 7883493 TI - Four-year outcome data for 400 laparoscopic cholecystectomy patients: recognition of persistent symptoms. PMID- 7883495 TI - The remaking of a surgeon. PMID- 7883494 TI - Laparoscopic approach to acute cholecystitis: a four year retrospective review. PMID- 7883496 TI - Laparoscopic surgery: cost, credentialing, training, safety and legal issues. PMID- 7883497 TI - The impact of laparoscopy on clinical cancer staging: a worldwide perspective. PMID- 7883498 TI - Laparoscopic colorectal resection: a review of the current experience. PMID- 7883499 TI - Improved efficiency in laparoscopic abdominoperineal resection: the Kim-Geis approach. PMID- 7883500 TI - Adoption of laparoscopic colectomy procedures: relationship to local factors and preceptorships. PMID- 7883501 TI - Benefits of complexity scales in laparoscopic colectomy. PMID- 7883502 TI - Laparoscopic colon surgery: some helpful hints. PMID- 7883503 TI - Laparoscopic colorectal surgery. A provocative critique. PMID- 7883504 TI - Laparoscopic colon surgery for cancer: controversy, caution and common sense. PMID- 7883505 TI - Laparoscopic appendectomy in the 1990's. PMID- 7883506 TI - Laparoscopic appendectomy. PMID- 7883507 TI - Recurrent appendicitis after laparoscopic appendectomy. PMID- 7883508 TI - Laparoscopic adrenalectomy. PMID- 7883509 TI - Advanced laparoscopic procedures for the non-advanced laparoscopic surgeon. PMID- 7883510 TI - Laparoscopy in general surgery: training, credentialing, and safety. PMID- 7883511 TI - Training, credentialing, economics and risk management in operative laparoscopy. PMID- 7883512 TI - Cost analysis of office surgery clinic with comparison to hospital outpatient facilities for laparoscopic procedures. PMID- 7883513 TI - [Antiretroviral therapy in adult HIV-infected patients]. PMID- 7883514 TI - [Modern treatment of primary osteoporosis]. PMID- 7883515 TI - [Is the value of antioxidative vitamins established?]. PMID- 7883516 TI - [Thrombolysis and coronary dilatation in therapy of acute myocardial infarct]. PMID- 7883518 TI - [Bile acids in therapy of liver diseases]. PMID- 7883517 TI - [Are proton pump inhibitors safe?]. PMID- 7883519 TI - [45-year-old patient with hepatosplenomegaly, polyneuropathy and M-gradient]. PMID- 7883520 TI - [27-year-old patient with nodules in the breast, tongue, subcutis and brain]. PMID- 7883521 TI - [Optimal dosage of acetylsalicylic acid in therapy of coronary heart disease]. PMID- 7883522 TI - [Which diuretic therapy in be used in patients with liver cirrhosis and hyponatremia, especially with possible kidney failure]. PMID- 7883523 TI - [During which time period after administration of streptokinase is renewed administration of this drug contraindicated?]. PMID- 7883524 TI - [Fever of unknown origin]. PMID- 7883525 TI - [Paraneoplastic syndromes]. PMID- 7883526 TI - [Diagnosis of function in angiology]. PMID- 7883527 TI - [Aspects of function in endocrine diagnosis]. PMID- 7883528 TI - [Spiroergometry]. PMID- 7883529 TI - [Measuring pulmonary artery pressure in analysis of pulmonary circulation]. PMID- 7883530 TI - [Noninvasive diagnosis of major circulatory function]. PMID- 7883531 TI - [Progressive loss of vision in suspected tumor]. PMID- 7883532 TI - [Liver transplantation in hemophilia A?]. PMID- 7883533 TI - [Treatment after myocardial infarct with ACE inhibitors. Are all problems solved by "mega-studies"?]. PMID- 7883534 TI - [16th Congress of the European Society of Cardiology and 12th World Congress of Cardiology, Berlin 10-14 September 1994]. PMID- 7883535 TI - [What are the treatment possibilities for myelodysplastic syndrome?]. PMID- 7883536 TI - [Hemorrhagic diathesis]. PMID- 7883537 TI - [Function tests in gastroenterology]. PMID- 7883539 TI - Mental health outreach program following the earthquake in Armenia: utilizing the nursing process in developing and managing the post-natural disaster plan. AB - This article provides a description of the eight phases of the Mental Health Outreach Program (MHOP) cofounded by the author to address the needs of the surviving community following the 1988 earthquake in Armenia. For the purposes of the MHOP, the nursing process was expanded from five to eight phases: 1) preassessment, 2) assessment, 3) analysis, 4) community diagnosis, 5) planning, 6) implementation, 7) evaluation, and 8) remodification. A framework for assessing the level of trauma in an unfamiliar community (with its mnemonic acronym COPE), which was formulated by the author to expedite the assessment and implementation phases, is described. The article concludes with a set of recommendations for psychiatric mental health nurses in mitigating the negative impact and consequences of disasters. PMID- 7883540 TI - Chinese perspectives on culture and mental health. AB - Central to providing culturally appropriate nursing care is sensitivity to and knowledge about the group being cared for. Although "mental health" and "mental illness" are artificial concepts among people who do not differentiate and treat mind, body, and spirit separately, and who may not differentiate illness from other problems of living, many individuals ethnically rooted in one or more Asian cultures enter Western mental health care systems. Quality nursing care requires understanding and respect for traditional values, beliefs, and practices that may differ significantly from those typical of Western European-based societies. Whether clients are traditional in orientation or highly acculturated to Western ways, nurses are responsible for providing culturally appropriate care. This article discusses mental health and nursing care from various perspectives of Asian and Asian-American clients, and in particular those of Chinese descent. PMID- 7883541 TI - Depression among Chinese Americans: a review of the literature. AB - The Chinese American population is among the fastest growing ethnic minority groups in the United States. Knowledge of the interaction between culture, disease expression, and utilization of psychiatric treatment by this population is limited. This article gives a general review of the literature on depression among Chinese Americans in order to clarify misconceptions, to increase knowledge of research on depression that has been done on one specific Asian-American group, and to set a direction for future nursing research and intervention. PMID- 7883542 TI - Reflections: waiting for death--a nursing response to a family grieving for a victim of terrorism. AB - This article is written from the perspective of the primary care nurse in Turkey and describes the emotional states of three sisters, one of whom was a nurse, while denying and then awaiting the death of their brother. He was shot by terrorists in the frontal lobe and was in intensive care. PMID- 7883543 TI - Safety of preoperative enoxaparin in head and neck cancer surgery. AB - BACKGROUND: Thromboembolism is a risk in major head and neck cancer surgery patients predisposed to thrombosis. This study was designed to determine whether enoxaparin (a low molecular weight heparin) administered prior to surgery induces perioperative bleeding. METHODS: Forty patients scheduled for major cervicofacial cancer surgery were randomized in a double-blind study to receive either 20 mg enoxaparin or placebo, 12 hours before surgery. Blood losses were measured at the end of surgery and 6 hours later. RESULTS: Bleeding was equal in the placebo group and in the enoxaparin group, with losses of 648 +/- 106 mL and 602 +/- 106 mL (p = 0.76), respectively. Six hours after surgery, blood collected was 159.3 +/- 25.7 mL in the placebo group vs 151.4 +/- 21 mL in the enoxaparin group (p = 0.81). CONCLUSION: Preoperative administration of enoxaparin is safe in head and neck cancer surgery, but further studies are required to evaluate its efficacy in preventing thromboembolism. PMID- 7883544 TI - Linac radiosurgery for locally recurrent nasopharyngeal carcinoma: rationale and technique. AB - BACKGROUND: Patients with locally recurrent nasopharyngeal carcinoma benefit from reirradiation. A main barrier to successful palliation or cure is dose limitation secondary to normal tissue tolerance. There are many strategies to increase the tolerated dose to the recurrent lesions. Stereotactic radiosurgery for the treatment of these lesions has rarely been reported. METHODS: Three patients with recurrent nasopharyngeal carcinoma were treated with linac-based stereotactic radiosurgery. RESULTS: One patient remained disease-free 1 year after radiosurgery; the second patient had neurologic deterioration of uncertain etiology (complication vs recurrence) 6 months after radiosurgery; and the third patient had local recurrence 6 months after radiosurgery. CONCLUSION: Stereotactic radiosurgery can be used to deliver a boost dose of radiation to recurrent nasopharyngeal carcinomas. The technique is increasingly available and may offer some advantages compared with other techniques. Treatment recommendations are presented. PMID- 7883545 TI - Color Doppler imaging for vocal cord palsy. AB - BACKGROUND: Conventional techniques of laryngoscopy for vocal cord palsy can sometimes be difficult or impossible to perform, and B-mode real-time ultrasonography has been previously reported by the authors to be helpful in these situations. In some cases, however, B-mode ultrasonography can be inconclusive. We investigated whether color Doppler imaging can significantly improve vocal cord examination in these cases. METHOD: Ten normal volunteers were examined using the Acuson 128XP/5 with a 7-MHz L7384 linear transducer. The thyroid cartilage was used as an acoustic window. Several distinct color flow patterns were observed with the subjects breathing quietly at rest, at the start of vocalization, and in prolonged phonation. Eight patients with hoarseness of voice were then examined by two separate observers in a double-blinded fashion. The first observer performed B-mode ultrasonography and color Doppler imaging, while the second observer performed indirect laryngoscopy and direct fiberoptic laryngoscopy. RESULTS: Laryngoscopy was used as the standard for comparison. B mode real-time ultrasonography correctly identified vocal cord palsy in three patients and normal vocal cords in one. The remaining four patients were reported as equivocal or normal. Color Doppler imaging correctly identified the problem in all eight patients. CONCLUSION: Color Doppler imaging for vocal cord examination is more sensitive than B-mode real-time ultrasonography, and seems to be as accurate as laryngoscopy in determining vocal cord palsy or paresis. PMID- 7883546 TI - Relationship between vocal cord paralysis and benign thyroid disease. AB - BACKGROUND: Vocal cord paralysis is generally associated with advanced thyroid malignancy. It may also be present in the setting of benign thyroid disease. This association may be incidental as well as causal. METHODS: Retrospective review of cases with concurrent diagnosis of vocal cord paralysis and benign thyroid disease. RESULTS: Eight cases found, all with documented vocal cord paralysis, by laryngoscopy. Four patients had nodular thyroid disease, but in two it was contralateral to the recurrent laryngeal nerve paralysis. The remaining patients had goiters of various sizes. Six patients were euthyroid, two on thyroid hormone replacement. Two patients were thyrotoxic: one had Graves' disease and the other had subacute thyroiditis. CONCLUSIONS: Vocal cord paralysis can be the result of benign thyroid disease by such mechanisms as compression, stretching, or inflammation. Malignant thyroid disease should always be ruled out in structural thyroid abnormalities. Vocal cord paralysis can also be an incidental finding unrelated to thyroid abnormality. PMID- 7883547 TI - Superior laryngeal nerve injury from thyroid surgery. AB - BACKGROUND: Injury to the recurrent laryngeal nerve is a well-recognized complication of thyroid surgery. Injury to the superior laryngeal nerve is less documented, perhaps due to the difficulty in recognizing its manifestations. This study was designed to document the incidence of injury to the superior laryngeal nerve in a series of patients who underwent thyroidectomy. METHODS: Twenty consecutive patients with thyroidectomy during a 9-month period underwent evaluation for superior laryngeal nerve injury 3 months postoperatively. Methods for evaluation included laryngeal videostroboscopy, laryngeal electromyography, and a subjective interview. RESULTS: One patient (5%) was diagnosed with unilateral superior laryngeal nerve injury. CONCLUSIONS: The risk of injury to the superior laryngeal nerve during thyroidectomy is significant, and the result may be devastating to those patients who rely on their voices professionally. Laryngeal videostroboscopy and electromyography may be necessary to diagnose superior laryngeal nerve injury. PMID- 7883548 TI - Anaplastic carcinoma of the thyroid: a 24-year experience. AB - BACKGROUND: Anaplastic carcinoma of the thyroid gland is a lethal entity; few patients live more than 12 months following diagnosis. We retrospectively reviewed the experience with this entity at our cancer institute and identified a subgroup of patients with complete resection who have a 60% 5-year survival. METHODS: Twenty-one cases of anaplastic carcinoma of the thyroid gland were analyzed retrospectively with respect to prognostic factors influencing survival. This represents 2.7% of 771 cases of thyroid cancer seen at our institution from 1968 to 1992. The median age at presentation was 65.1 years; male/female ratio was 1:1.1; and the most common symptom was a rapidly enlarging neck mass (76%). RESULTS: Estimated 5-year survival was 10% (median: 4.5 months). Tumor size less than 6.0 cm (p = .004) and female gender (p = .02) were significant prognostic factors. Five patients who underwent complete resection had an estimated 5-year survival of 60% (median: 131 months). Four of these patients had postoperative radiotherapy with or without sequential chemotherapy. Two of these patients survived more than 10 years, and a third remains alive without disease at 26 months. PMID- 7883550 TI - Pregnant woman with a neck mass. AB - None of the consultants was comfortable with the idea of proceeding with the biopsy of a neck mass in an outpatient clinic setting. All warned about the possible relationship of the mass with important anatomic structures. With regard to needing further information, physicians requested an imaging study of the neck, thoracic cavity, and mediastinum (Dr. Cummings); pelvic examination, breast examination with mammography, chest x-ray, and CBC (Dr. Weymuller); flexible endoscopy, chest x-ray, CBC, and MRI (Dr. Woodson). All three experts advised her to put IVF on hold. After the work-up, they would proceed with a biopsy of the mass and send the tissue to the pathologist in saline. In addition, tissue should be examined for fungus and AFB (Drs. Weymuller and Woodson). Because the patient proceeded with IVF and became pregnant, two experts advised her to abort and proceed with treatment for her Hodgkin's disease (Drs. Cummings and Woodson). The other option was for her to continue her pregnancy and proceed with radiotherapy to her neck, with shielding of the abdomen (Dr. Weymuller). PMID- 7883549 TI - DNA content in adenoid cystic carcinomas. AB - BACKGROUND: A retrospective study was performed on 51 patients with adenoid cystic carcinomas to see whether DNA ploidy, tumor stage, and histopathologic grading correlated with prognosis. METHODS: Histopathologic grading was performed according to Szanto et al and DNA content was estimated from archived material using the technique by Hedley et al. RESULTS: Thirty-nine tumors were DNA diploid and 12 were DNA aneuploid. Histologic grade III was more often associated with DNA aneuploidy than the lower grades (p = 0.011). DNA ploidy also correlated with clinical stage (p = 0.011). Log-rank analysis and Cox regression analysis of treatment failures revealed significant findings for S-phase value and DNA ploidy. CONCLUSIONS: Our results indicate that DNA ploidy estimations, S-phase value, and histologic grading are prognostic factors in adenoid cystic carcinomas. These examinations should therefore be incorporated in the evaluation of patients with adenoid cystic carcinomas. PMID- 7883551 TI - In situ skin grafting of free muscle flaps prior to microvascular transfer to provide intraoral lining for full-thickness defects. AB - BACKGROUND: Previously, the importance of providing skin for intraoral lining for full-thickness mucocutaneous defects has been emphasized. More recently, simple skin grafting of the intraoral portion of muscle flaps has been described. METHODS: Six patients were evaluated who had full-thickness mucocutaneous defects reconstructed by means of free muscle flaps with skin grafting of the intraoral muscle surface. An illustrative case is provided. A technique of preplacing the skin graft on the muscle prior to microvascular transfer is described. Mucosal biopsies were performed at the reconstruction site. RESULTS: All patients had complete take of the skin grafts. No fistulas occurred. Functional and esthetic results were satisfactory. CONCLUSIONS: The ideal candidate for this form of reconstruction is one in whom there is a large, full-thickness mucocutaneous defect. Preplacement of the skin graft reduces ischemia time, allows suturing of the skin graft to the muscle surface outside the narrow confines of the oral cavity, and enables placement of multiple quilting sutures that secure the graft against shear forces and so obviate the need for a stent dressing. PMID- 7883552 TI - Kaposi's sarcoma of the oral cavity in a non-AIDS patient: case report and review of the literature. AB - BACKGROUND: Not every patient with Kaposi's sarcoma (KS) has acquired immunodeficiency syndrome (AIDS). The "classic" form of KS is rare, and is associated with an indolent course. It is very distinct from AIDS-associated KS in which oral involvement is common and may be the initial presenting feature of this disease. Two other types of KS are recognized, the African and renal transplant-associated, which also are rarely associated with oral involvement. METHODS: We present the case of a 76-year-old man of Mediterranean ancestry who was found to have a biopsy-proven classical KS lesion of the hard palate. The patient was followed by the Radiation Therapy and Otolaryngology Services during and after his treatment. A review of the literature was also conducted. RESULTS: Radiotherapy was ineffective at a dose considered "standard" for KS in AIDS patients (1,500 cGy), but was effective when continued to 4,800 cGy. A 24-month follow-up showed no evidence of recurrence in the oral cavity. CONCLUSIONS: KS of the oral cavity, is almost always associated with AIDS in the United States, However, it can occur in any of the four types of KS. Although this neoplasm is typically highly radiosensitive, the treatment for each patient needs to be individualized. PMID- 7883553 TI - Bilateral chylothorax following neck dissection. AB - BACKGROUND: Bilateral chylothorax, as a complication of neck dissection, is extremely rare, and was first described in 1907. Ten cases are reported in the literature. METHODS: This presentation illustrates an additional case of bilateral chylothorax occurring after neck dissection. Anatomic and physiologic considerations are presented and possible mechanisms of pathogenesis are discussed. RESULTS: Chylothorax has two major complications: respiratory and metabolic. The modern concepts of treatment are summarized. CONCLUSIONS: After neck dissection, the clinician should suspect chylothorax if the patient had respiratory embarrassment and an abnormal chest x-ray postoperatively. PMID- 7883554 TI - Risk factors for complications in clean-contaminated head and neck surgical procedures. AB - BACKGROUND: Contamination of a head and neck surgical wound with oropharyngeal secretions has been shown to dramatically increase the incidence of wound complications. Appropriate perioperative antibiotic prophylaxis has significantly reduced contaminated wound infection rates in several previous reports. The current study examined multiple patient parameters to determine risk factors for all perioperative complications following clean-contaminated head and neck surgical procedures. METHODS: Retrospective review of medical records from 159 patients who underwent clean-contaminated major head and neck surgical procedures at the University of Washington between 1985 and 1991. More than 30 preoperative and operative parameters were evaluated, and all complications were recorded. The data were examined using a multivariate statistical analysis. RESULTS: An overall complication rate of 63% included 22% with wound infections (oro/pharyngocutaneous fistula or purulent drainage), 22% with other types of infections, and 51% with noninfectious complications. The overall perioperative mortality rate was 1.2% (two patients). Prior radiotherapy, operative time, perioperative transfusion, and flap reconstruction were all associated with a significantly higher overall complication rate (p < or = 0.05). Only prior radiotherapy therapy correlated with an increase in wound infection rate (p = 0.05). CONCLUSIONS: Prior radiotherapy significantly increases the risk of perioperative complications and wound infections following clean-contaminated head and neck surgical procedures. Other factors reflecting the complexity of the procedure also influence the overall complication rate. PMID- 7883555 TI - Treatment of extrathyroidal extension from papillary thyroid cancer. PMID- 7883556 TI - Radioactive materials in recycled metals. AB - In recent years, the metal recycling industry has become increasingly aware of an unwanted component in metal scrap--radioactive material. Worldwide, there have been 35 instances where radioactive sources were unintentionally smelted in the course of recycling metal scrap. In some cases contaminated metal consumer products were distributed internationally. In at least one case, serious radiation exposures of workers and the public occurred. Radioactive material appearing in metal scrap includes sources subject to licensing under the Atomic Energy Act and also naturally occurring radioactive material. U.S. mills that have smelted a radioactive source face costs resulting from decontamination, waste disposal, and lost profits that range from 7 to 23 million U.S. dollars for each event. To solve the problem, industry and the government have jointly undertaken initiatives to increase awareness of the problem within the metal recycling industry. Radiation monitoring of recycled metal scrap is being performed increasingly by mills and, to a lesser extent, by scrap processors. The monitoring does not, however, provide 100% protection. Improvements in regulatory oversight by the government could stimulate improved accounting and control of licensed sources. However, additional government effort in this area must be reconciled with competing priorities in radiation safety and budgetary constraints. The threat of radioactive material in recycled metal scrap will continue for the foreseeable future and, thus, poses regulatory policy challenges for both developed and developing nations. PMID- 7883557 TI - Use of risk projection models for the comparison of mortality from radiation induced breast cancer in various populations. AB - The aim of our study is to compare lifetime risk estimates for radiation-induced breast cancer between various populations. Some epidemiological studies, mainly on Japanese A-bomb survivors, but also on North American populations irradiated for medical reasons, provide risk coefficients for excess mortality from breast cancer after exposure to ionizing radiation. For this comparative study, these risk coefficients have been transferred into the Japanese, American, and French populations, using demographic data, risk projection models, and assuming an individual acute exposure. The lifetime risk estimates are similar in the three populations when the additive projection model is used because of the similarity of the life tables of the three countries. However, using the multiplicative model, large differences appear due to the discrepancies in the baseline breast cancer rates between the Japanese and Occidental populations. It is for this reason that transfer of risk coefficients fitted on the Japanese population data must be considered with caution when applied to an Occidental population. Lifetime risk estimates for a given population, the French population for example, are largely dependent on the risk coefficients considered from various epidemiological studies. Nevertheless, for each source of data, they are higher with the multiplicative model than with the additive one. Moreover, it should be noted that data from medical irradiation lead to higher risk estimates when using the additive model, whereas studies of the A-bomb survivors lead to higher risk estimates with the multiplicative model. This comparative study points out the variations of the lifetime risk calculations according to the baseline breast cancer mortality rates of the three populations and with the use of different mathematical projection models. PMID- 7883558 TI - The Utah Leukemia Case-Control Study: dosimetry methodology and results. AB - This paper discusses the dosimetry methodology used to estimate bone marrow dose and the results of dosimetry calculations for 6,507 subjects in an epidemiologic case-control study of leukemia among Utah residents. The estimated doses were used to determine if a higher incidence of leukemia among residents of Utah could have been attributed to exposure to radioactive fallout from above-ground nuclear weapons tests conducted at the Nevada Test Site. The objective of the dosimetry methodology was to estimate absorbed dose to active marrow specific to each case and each control subject. Data on the residence of each subject were available from records of the Church of Jesus Christ of Latter-day Saints. Deposition of fallout was determined from databases developed using historical measurements and exposure for each subject from each test was estimated using those data. Exposure was converted to dose by applying an age-dependent dose conversion factor and a factor for shielding. The median dose for all case and control subjects was 3.2 mGy. The maximum estimated mean dose for any case or control was 29 +/- 5.6 mGy (a resident of Washington County, UT). Uncertainties were estimated for each estimated dose. The results of the dosimetry calculations were applied in an epidemiological analysis. PMID- 7883559 TI - The Utah Thyroid Cohort Study: analysis of the dosimetry results. AB - Above ground testing of nuclear weapons at the Nevada Test Site (NTS) during the 1950s created radioactive fallout that was dispersed into the atmosphere and deposited over a large geographical area of the U.S. One area believed to have received a considerable amount of exposure to radioiodines (131I and 133I) in the fallout was southwest Utah and southeast Nevada. This paper describes the estimates of doses to the thyroid for a cohort of 3,545 subjects who were children during the atmospheric testing period. This group of children was examined for thyroid disease during 1965-1970 and again in 1985-1986. The cohort was made up of children who lived in three counties in 1965: Washington County, Utah; Lincoln County, Nevada; and Graham County, Arizona (originally thought to be an unexposed group). Pathway analysis was used in the dosimetry, considering exposures through the ingestion of milk and vegetables, inhalation of iodine during the passage of the fallout cloud, and external exposure. Specific data were obtained on diet (including sources and levels of milk and vegetables consumed, residence history, and lifestyle) by interviewing the parents or nearest living relative of subjects. The final dosimetry file for each member of the cohort contained specific doses to the thyroid glands and uncertainties (reported as geometric standard deviations, GSD) related to each dose estimate. The mean absorbed dose to the thyroid for subjects living in Washington County, Utah, was 170 mGy; for Lincoln County, Nevada, 50 mGy; and for those living in Graham County, Arizona, 13 mGy. The maximum dose to any subject was 4,610 mGy. There were 10 subjects who had doses greater than 1 Gy. The majority of uncertainty values calculated in this study were GSD values between 2.0 and 4.0. The results of the dosimetry were combined with the results of clinical examinations of the cohort to determine if a causal relationship exists between dose to thyroid from NTS generated radioactive iodines and the incidence of thyroid disease. PMID- 7883560 TI - Fractional absorption of ingested uranium in humans. AB - This paper provides a review and reanalysis of data relating to gastrointestinal (GI) uptake of uranium in humans. Estimates of GI uptake of uranium in adult humans have been derived from results of three controlled experimental studies involving short-term oral intake of an elevated quantity of uranium in fluids, from a controlled balance study conducted in a metabolic research ward of a hospital, and from a variety of environmental studies in which urinary uranium could be related to total intake or total excretion of this element in the same population. For controlled studies, uptake values range from less than 0.1% to about 6% for individual subjects, with central values for different studies falling in the range 1-2.4%. Environmental studies yield central estimates in the range 0.3-3.2%. Expressed as a percentage of total intake of uranium in food and fluids, average GI uptake of uranium in adult humans appears to be about 1-1.5%. Limited intake and excretion data for environmentally exposed human subjects > or = 5 y of age do not reveal important differences with age in uranium uptake, but more definitive information is needed for children. More information is also needed to determine whether fractional uptake of uranium increases with decreasing levels of intake and whether uptake from drinking water is substantially higher than uptake from food. Data for laboratory animals indicate that fractional uptake of uranium depends strongly on the chemical form ingested and the length of time since the last intake of food. PMID- 7883561 TI - Tritium concentrations of blood samples collected throughout Japan. AB - Tritium concentrations were measured for blood samples collected from 20 cities throughout Japan during 1989-1990. The mean 3H concentration was found to be 1.4 +/- 0.4 Bq L-1 and 1.0 +/- 0.4 Bq L-1 (combustion water) for free water 3H and organically-bound 3H, respectively, excluding the abnormally high data of one city. The organically-bound 3H contents clearly depended on the latitudes of sampling locations, although the free water 3H concentrations showed no correlation with the latitudes. Organically-bound 3H is considered to be more suitable than free water 3H as an indicator of long time 3H exposure to human. PMID- 7883562 TI - Trends of population radiation absorbed dose from diagnostic nuclear medicine procedures in Iran: 1985-1989. AB - In view of the rapid expansion of diagnostic nuclear medicine procedures in Iran, this study was undertaken to examine trends of nuclear medicine practice in the country and to determine the mean effective dose equivalent per patient and per capita. Comprehensive national data covering 93% of all nuclear medicine centers in 1985-1989 were obtained. The total number of nuclear medicine examinations increased by 42% during these years. The relative frequency of thyroid investigations was 84% followed by liver/spleen and bone procedures (7% and 6%, respectively). 99mTc was the radionuclide of choice for 86% of investigation while 131I alone accounted for 59% of collective effective dose equivalent. The annual average number of nuclear medicine procedures per 1,000 people was 1.9. For the thyroid, the highest number (48%) of patients investigated was in the 15 29 y age group and the lowest (3%) was in the > 64 y age group. The male to female ratio of thyroid and cardiac patient was 0.18 and 3.64, respectively. The numbers of males and females studied for the remaining eight procedures were less frequent and about the same. The mean effective dose equivalent per patient and per capita was about 4.3 mSv and 8 microSv, respectively. 131I was responsible for most of collective effective dose equivalent produced by nuclear medicine. Therefore, future efforts should be concentrated on dose reduction for diagnostic 131I tests. PMID- 7883563 TI - Formulation of the reference Indian adult: anatomic and physiologic data. AB - Data on heights and weights of Indian males and females of various ages are presented. The weights of specific organs obtained from post-mortem records of accident cases of Indian adults and children are also presented to provide some inputs towards formulation of an Indian Reference Man for radiation protection purposes. An intercomparison of the present data with the data available from other sources including those for ICRP Reference Man, Woman, and Child has been made. The daily intakes of air, water, and dietary constituents of an average Indian adult are also given. PMID- 7883565 TI - Calculation of dose, dose equivalent, and relative biological effectiveness for high charge and energy ion beams. AB - The Green's function for the transport of ions of high charge and energy is utilized with a nuclear fragmentation database to evaluate dose, dose equivalent, and RBE for C3H10T1/2 cell survival and neoplastic transformation as a function of depth in soft tissue. Such evaluations are useful to estimates of biological risk for high altitude aircraft, space operations, accelerator operations, and biomedical applications. PMID- 7883564 TI - A comparison of techniques used to estimate the amount of resuspended soil on plant surfaces. AB - The objectives of this study were to compare four common techniques used to estimate soil mass loadings on plant surfaces and to assess the need to account for particle-size distributions of both the soil tracer and contaminant of concern within the soil. Soil loadings (g soil kg-1 dried plant) from split samples collected in a pasture near Chernobyl were estimated using soil tracers of plutonium analyzed via alpha spectroscopy (mean +/- standard error; 1.0 +/- 0.2), titanium analyzed with an inductive coupled plasma spectrometer; (3.6 +/- 0.6), and neutron activation analysis for scandium (8.1 +/- 1.6), as well as simply washing the soil off the vegetation (34.1 +/- 5.6) Differences were significant at p < 0.001. We also found that soil loading estimates from any one technique varied by a factor of 10 depending on the soil particle size used in the calculations. This was because soil loadings decreased when smaller-sized soil fractions dominated the resuspension process. However, the percent of the plant's total contamination attributable to soil loading increased with smaller soil particles. Smaller soil particles apparently contribute less to the mass of soil loading (g soil kg-1 dry plant), but more to the total plant contamination (Bq) because of the higher concentration of contaminant found in the smaller sized soil fractions. Differences in mass loading estimates due to the technique chosen (a factor of 10), or due to differences in elemental concentration as a result of the soil particle size used in the calculation (also a factor of 10), were greater than the natural variability observed in the field (2.5). PMID- 7883566 TI - Testing the conservativeness of a screening model in a model validation exercise. AB - Although models for calculating derived emission limits have been around for many years, the opportunity to test them against independent data sets did not arise until the Biospheric Model Validation Study (BIOMOVS) was organized in 1985. Within BIOMOVS, two scenarios tested predictions of the movement of 131I and 137Cs from air to soil, pasture, milk, and beef. One of these scenarios was a model intercomparison of a chronic release over 30 y. The second scenario, using data gathered world-wide after the Chernobyl accident, allowed predictions to be compared directly with observations. The Canadian Standards Association's Guidelines for Calculating Derived Release Limits for Radioactive Material in Airborne and Liquid Effluents for Normal Operation of Nuclear Facilities was tested in both these scenarios to see whether its predictions were suitably conservative, as they should be for a screening model. A comparison was made between results of the Canadian Standards Association's model and those of other screening models on the one hand and results of models attempting to predict best estimates on the other hand. This analysis shows that often screening models are not conservative, and thus there should be much more effort to test the models against observations. PMID- 7883567 TI - An automated gross alpha/beta activity monitor applied to time-resolved quantitative measurements of 222Rn progeny in air. AB - Automated monitors for the determination of airborne radioactivity are widely in use as early warning systems for nuclear emergencies; however, the data acquired for this purpose are seldom used for analyzing spatial and temporal variations of natural radioactivity (especially radon and short-lived decay products). This paper shows that a specific type of airborne gross alpha/beta activity monitor, applied in several European emergency networks, can be effectively used to study the transport of 222Rn progeny in the outdoor environment. Real-time recordings (10-min sampling time) can, independent of the actual equilibrium ratio, be converted to the equilibrium-equivalent decay-product concentration (EEDC) of 222Rn. Medium volume air sampling and a slow-moving tape air sampler yield a low detection limit of < or = 0.1 Bq m-3. This paper further describes all factors and processes contributing to the uncertainty in the data obtained in this way; the total error in single recordings is estimated at 20-25% (95% confidence interval). Data of 222Rn progeny obtained from the Dutch National Radioactivity Monitoring network agree with results of other radon surveys. PMID- 7883568 TI - Monte Carlo simulation of radon emanation from dry building materials. AB - Prediction of radon release from building materials is a general problem. Since it is impractical to follow each recoil radon path and measure the surface area of porous texture by experimental methods, a powerful computer simulation approach is conducted in this paper. The Monte Carlo simulation program TRIM, based on the momentum and energy conservation of the ion transport in matter, is modified to simulate the recoil path in a 3-D frame. A follow-up Monte Carlo program was established further to calculate the detailed recoil range distribution and the recoil probability (emanating power). The powerful Turning Bands Method (TBM) of random field is applied to simulate the 3-D porous texture based on the porosity and the correlation function of the porous texture. Based on the simulated porous texture, the fractal dimension of the surface is calculated and used to calculate the effective surface area for radon recoil. The relations between the air buffer thickness, embedding effect of recoil, and the measuring scale of the surface area for the porous texture are discussed and numerically calculated. After these calculations are performed, the relations between the emanating rate, surface area, material density, and porosity are established to calculate the radon emanation rate from porous materials. This paper provides a clear theoretical picture of the mechanism of radon release from the building materials. It has also potential application to the recoil release calculations of other radioactive elements from solid materials. PMID- 7883569 TI - Estimates of inhalation doses resulting from the possible use of phospho-gypsum plaster-board in Australian homes. AB - Current materials used as internal lining in Australian buildings are based on natural gypsum of low radium content. A study was carried out to estimate the contribution to the annual effective dose due to airborne contamination from chemical by-product gypsum plaster-board of higher radium content if it were used as an internal lining. The 226Ra content and 222Rn exhalation rate were measured for several samples of the plaster-board, and the behavior of 222Rn and its progeny (218Po, 214Pb, 214Bi, and 214Po) in a typical building was modeled numerically, using the results of the exhalation rate measurements as input. For building ventilation rates greater than approximately 0.5 air changes per hour, the contribution to the total annual effective dose from inhalation of 222Rn and its progeny exhaled from the phospho-gypsum plaster-board is estimated to be below 1 mSv. This contribution is reduced if the surface of the plaster-board is coated with paint or cardboard, or if the very fine particles are removed from the phospho-gypsum during manufacture of the plaster-board. The effective doses arising from dust generation during the installation of the plaster-board are also estimated to be below 1 mSv. The recommended action level of 200 Bq m-3 for radon in air in Australia corresponds to an annual effective dose of approximately 6 mSv. The study indicates that the suggested acceptable level of 185 Bq kg-1 for the 226Ra concentration in the plaster-board may be too restrictive under Australian conditions. PMID- 7883570 TI - Dose measurement for 89Sr chloride injection. PMID- 7883571 TI - Video display terminal very low frequency measurements: the need for protocols in assessing VDT user "dose". AB - It has been well established that video display terminals (VDTs) which employ the use of a cathode ray tube produce electric and magnetic fields of varying frequencies. Numerous studies have attempted to relate magnetic field exposure from VDTs in the extremely low frequency (ELF) and very low frequency (VLF) bands to adverse pregnancy outcome. Initial studies utilized VDT use time as a surrogate assessment of exposure, while later studies have obtained actual measurements. These measurements have been typically obtained at fixed distances from the screen. While VDT measurement criteria have been established for measuring VDT fields, criteria for the assessment of VDT user exposure has not. VLF magnetic and electric field measurements from approximately 140 and 40 different VDTs, respectively, were obtained over a 3-y period at the following positions: 0.50 m from the vertical centerline of the screen and at the approximate location of VDT user reproductive organs--0.30 m above the seat of the VDT operator in the working position. The measurement results of the two aforementioned locations were compared and demonstrate very little correlation. This lack of correlation indicates that VDT operator exposure assessment criteria are needed to determine any dose-response relationship between VDT electric and/or magnetic fields and adverse health implications. PMID- 7883572 TI - Electron paramagnetic resonance dosimetry of dentine following removal of organic material. AB - The feasibility of using dentine from surgically extracted human teeth as in vivo dosimeters was investigated. The organic fraction of human dentine was removed by Soxhlet extraction with diethylenetriamine. The specimens were then crushed and 75 to 250 microns granules were given doses of gamma radiation ranging from 50 mGy to 8 Gy. Following irradiation, electron paramagnetic resonance spectra were collected. Signals were detected with Lande factors of g = 2.0018, line width = 0.903 mT; and g = 1.9961, line width = 0.444 mT. These signals have both been reported for hydroxyapatite of bone and enamel. Several other signals were also seen but not characterized. It was concluded that doses of 500 mGy or less may be resolved with prior removal of the organic component of dentine. PMID- 7883573 TI - Potential effects of surface water components on actinide determinations conducted by ion chromatography. AB - An elution program for separating actinides (thorium, uranium, neptunium, plutonium, americium, and curium) on low hydrophobicity ion exchange columns was evaluated for solutions spiked with actinides and common surface water components. Potential interferences from dissolved ions (Na+, K+, Ca2+, Cl-, and SO(4)2-), humic acid, and radium were investigated. Sulfate levels greater than 0.25 mumol interfered with separation of americium, curium, and plutonium. Humic acid levels above 100 micrograms produced distinct widening of actinide peaks and reduced actinide recoveries. These interferences limit the range of useful sample volumes and create a need for sample pretreatment procedures. No interferences were produced by 0.025 to 2.5 mumol Ca2+, 0.045 to 4.5 mumol Na+, 0.015 to 1.5 mumol K+, and 0.025 to 4.5 mumol Cl-. In the absence of interferences, the program effectively separated radium from the actinides. PMID- 7883574 TI - 222Rn variations in Mystery Cave, Minnesota. AB - 222Rn concentrations and meteorological parameters were measured at 4-h intervals over a 2-y period in Mystery Cave, southeastern Minnesota. Continuous radon monitors and meteorological sensors connected to data loggers were installed at several locations along commercial tour routes. 222Rn concentrations ranged as high as 25 kBq m-3 in summer and 20 kBq m-3 in winter. Average winter concentrations were lower than summer by at least a factor of two. Seasonal radon variations were correlative with outside air temperatures. During the winter, radon concentrations were observed to fluctuate periodically by factors of 20 or more in under 24 h. Both the long- and short-term variations are correlative with temperature-induced mixing of cave air with surface air. PMID- 7883575 TI - A survey of films for use as dosimeters in interventional radiology. AB - Analysis of radiation doses in interventional radiological procedures that can lead to deterministic radiation effects such as erythema and epilation would assist physicians in planning patients care after exposure and in reducing doses. Photographic films used to measure skin exposure in the past are too sensitive for the high doses involved in interventional procedures. Seventeen different types of films, many of which are generally available in hospitals, were surveyed to see if any would meet the demands of interventional radiology. Sensitometric curves obtained demonstrate that most films are inappropriate for high dose procedures. Using Kodak Fine Grain Positive and Dupont duplicating films and automatic processing, doses as high as 2.8 Gy could be measured with reasonable accuracy. Similar results can be obtained by manually processing Kodak XV-2 verification film at room temperature. PMID- 7883576 TI - Generic values of model transfer parameters and corresponding post-Chernobyl experimental evaluations. PMID- 7883577 TI - The potential for bidirectional promoter activity of the human PDGF-A chain gene. AB - Platelet-derived growth factor (PDGF) is a heterodimeric glycoprotein consisting of A and B chains. A functional promoter had been identified in the 5' flanking region of the human PDGF-A chain gene. We found that the PDGF-A chain promoter region possesses the potential for bidirectional activity. This bidirectional promoter activity is influenced by the 5'-untranslated region (5'-UTR) and serum concentration. The 5'-UTR may regulate expression of the PDGF-A chain by transcription in the opposite direction. PMID- 7883578 TI - Serum and urinary type IV collagen concentrations in the assessment of diabetic microangiopathy. AB - We investigated the role of measurement of serum and urinary type IV collagen (IV C) levels in monitoring diabetic microangiopathy. Furthermore, we compared these levels in diabetic nephropathy and non-diabetic renal disease (NDRD). A one-step sandwich enzyme immunoassay was used to measure IV-C levels in 82 diabetic patients, 33 NDRD patients and 20 healthy non-diabetic control subjects. The diabetic patients were classified into four groups according to urinary albumin/creatinine index (ACI) (mg/g) and serum creatinine (s-Cr) (mg/dl): normoalbuminuria (ACI < 30), microalbuminuria (ACI 30-300), albuminuria (ACI > 300, s-Cr < 1.99 mg/dl) and renal insufficiency (s-Cr > 1.99 mg/dl). Serum and urinary IV-C levels were significantly elevated even in diabetic patients without clinical evidence of microangiopathy compared with control subjects (p < 0.05 and p < 0.01, respectively). Both levels were significantly higher in normoalbuminuric patients than in the control subjects, and in patients with microalbuminuria, albuminuria or renal insufficiency than in normoalbuminuric patients, with significant differences between these groups (serum and urinary IV C, both p < 0.0001 by ANOVA). Urinary IV-C and albumin levels were significantly correlated, even in normo- and microalbuminuric patients (r = 0.55, p < 0.0001). Serum IV-C in normoalbuminuric patients rose significantly as the degree of retinopathy progressed from background to proliferative stages (p < 0.05). Neither serum nor urinary IV-C levels were influenced by glycemic control. Albuminuric diabetic patients (with and without renal insufficiency) had significantly higher levels of serum IV-C compared with those in proteinuric NDRD patients (p < 0.005), though there was no significant difference in the urinary IV-C level. However, the urinary IV-C/albumin ratio was significantly higher in albuminuric diabetic patients than in proteinuric NDRD patients, even after adjusting for s-Cr and creatinine clearance (p < 0.0001). In conclusion, we suggest that measured serum and urinary IV-C concentrations may serve as new markers for monitoring the development and progression of diabetic microangiopathy, particularly nephropathy. Furthermore, the measurement of serum IV-C concentrations and urinary IV-C/albumin ratios in diabetic patients may allow diabetic nephropathy and non-diabetic renal disease to be differentiated. PMID- 7883579 TI - Effectiveness of assistance circulations for distal circulatory support during cross-clamping of the descending thoracic aorta. AB - In order to find the ideal distal circulatory support during cross-clamping of the descending thoracic aorta, the author compared the effects of simple shunting (SS) and centrifugal pump (CP) on hemodynamics and metabolisms in mongrel dogs. In group I (control), the aorta was cross-clamped for two hours without SS or CP; in group II (SS), a temporary shunt was placed between the left common carotid and left femoral arteries during cross-clamping; in group III (CP), with left heart bypass, the flow was maintained about the same as that in group II; in group IV (CP), proximal pressure was maintained unchanged. Hemodynamic and metabolic parameters were recorded prior to cross-clamping and every 30 min for four hours during and after cross-clamping. All animals in group I suffered from hemodynamic instability, metabolic abnormalities and neurologic injury and died within 12 hours. Hemodynamic changes were more unstable in group III than in groups II and IV. Three dogs in group III and also in group IV but none in group II, suffered from neurologic injury. Metabolic changes in groups II, III and IV were not significant. The author conclude that hemodynamic and metabolic abnormalities can be minimized through the efficient use of a shunt in cross clamping of the descending thoracic aorta and postoperative complications such as paraplegia, renal failure and hepatic dysfunction can be prevented. The centrifugal pump as a distal circulatory support device is able to maintain stable hemodynamics and normal distal organic metabolisms if aortic pressure proximal to the clamp is maintained essentially unchanged through regulation of pump flow. However, it is unable to prevent paraplegia during cross-clamping of the descending thoracic aorta for two hours. Shortening the time of cross clamping of the descending thoracic aorta is necessary to prevent paraplegia. PMID- 7883580 TI - TJS-010, a new prescription of Kampo medicine with putative antidepressive and anxiolytic properties.--A behavioral study using experimental models for depression and anxiety. AB - We investigated the effect of TJS-010, a new prescription of Kampo or oriental medicine, on the locomotor activity and body temperature in rats in order to determine its antidepressive and anxiolytic effects. Tetrabenazine(TBZ), which sometimes induces depression in humans, decreased the spontaneous locomotion in rats, and attenuated the content of amines in several regions in the rat brain when intraperitoneally injected. TJS-010 was orally administered at a concentration of 750 mg/kg, and inhibited the locomotor suppression. The content of amines was not, however, altered. These results indicate that TJS-010 postsynaptically modulates the transmission or transduction. Imipramine, 5mg/kg, also enhanced locomotion in TBZ-treated rats, which was similar to the effect of TJS-010. These results suggest that TJS-010 has an antidepressive effect. TJS-010 also facilitated the hypothermia induced by subcutaneous injection of 0.1 mg/kg (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT), which is known to be mediated by serotonin-1A receptors. The hypothermia in the rats via an activation of serotonin-1A receptors is often observed with anxiolytic drugs. These results may raise the possibility that TJS-010 has an anxiolytic property. TJS-010 may serve as a useful drug for the treatment of those who suffer from depressive and anxiety disorders. PMID- 7883581 TI - Effect of immunomodulatory artificial blood exchange (IABX) on guinea pig-to-rat heart xenografts. AB - The aim of this study was to assess the effectiveness of pregraft immunomodulatory artificial blood exchange (IABX) in a guinea pig-to-rat xeno discordant heart transplantation, using an artificial blood (FC43 emulsion: The Green Cross, Japan) in exchange for a large volume of whole blood to remove humoral immune factors en bloc from the recipient rat. In the rats treated with IABX, rhythmic beating of the grafted heart was maintained for 2 hr, whereas the untreated heart beat lasted for only 15.2 +/- 5.2 min (n = 6). In the graft hearts treated with IABX, no pathologic changes such as multiple coronary thromboses due to hyperacute rejection (HAR) were observed. Humoral immune factors (natural-IgM titer, ACH50 and CH50 complement activities, platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen serum concentration), which are thought to contribute to HAR, decreased significantly following the IABX treatment. We conclude that IABX is an efficient method for prolonging the survival time of guinea pig heart xenografts by inhibiting thrombus formation in the xeno-graft heart. It was confirmed that IABX could remove recipient humoral immune factors en bloc. PMID- 7883582 TI - Indoor air quality and ventilation strategies in the use of combustion space heating appliances in housing. AB - Indoor air quality (IAQ) in the use of combustion appliances is important for adequate evaluation of air pollution health risks. Since people spend most of their time inside buildings, especially the elderly and children, their exposure to indoor air contaminants can increase health problems in the community. Combustion materials emitted from combustion space heating appliances in housing during the winter may become a serious problem to health, since sources of ventilation are usually left closed to obtain a comfortable temperature level. To evaluate the IAQ and factors that may decrease combustion materials emitted from heaters, a study was done by using a house exposure model. The study found that IAQ in an unventilated house during combustion heater use was poor due to lack of fresh air. When using a heater, natural ventilation should be used to dilute air contaminants emitted from the heater. A concentration of carbon dioxide at about 1000 ppm and a comfortable temperature of 20 degrees C could be maintained by applying natural ventilation of about 0.12 m2 during the use of an unvented kerosene space heater. However, ventilation also depends on the number of the occupants and the wind velocity. The use of a steamer is also important to provide optimum humidity levels without elevating the respirable dust concentration above the acceptable limit. PMID- 7883583 TI - Findings of transesophageal echocardiographic images in placing the coronary sinus perfusion catheter. AB - In retrograde cardioplegia (RCP), some difficulty is occasionally encountered when inserting a catheter into the coronary sinus (CS). Although the usefulness of transesophageal echocardiography (TEE) for guiding the cannulation procedures has been previously reported by other authors, we have obtained additional findings by TEE monitoring of eleven patients during placement of the CS catheter. The diameter of the CS ranged from 5.5 to 10.7 mm, indicating that it was large enough for the CS catheter to be inserted and that the resistance at insertion was not due to narrow CS. The precise time for inserting the catheter, for which myocardial protection is delayed, ranged from 8 to 376 seconds, with an average of 98 seconds. Dislodgement of the catheter was found in two cases. In case of difficult cannulation, the catheter tip was found to be pushing the right atrial wall adjacent to the CS orifice or alternatively it entered the middle cardiac vein which had a common atrial orifice with the CS in this particular case. We found that the knowing the following technical problems helps appropriate monitoring: the catheter tip becomes unclear when it is not perpendicular to the ultrasonic beam, when surgeon's fingers are placed behind the heart, or when the blood is entirely exsanguinated. Finally we present the possibility of employing images of overflow out of CS during RCP infusion, detected by TEE, as an index of efficient perfusion at the interventricular septum. PMID- 7883584 TI - Pharmacokinetic behavior of cyclosporine A in liver dysfunction. AB - The pharmacokinetic behavior of cyclosporine A (CyA), known as a potential immunosuppressive agent to prevent graft rejection in transplantation, was studied in patients with acute hepatitis and primary biliary cirrhosis (PBC). The ratios of blood concentration of total CyA (CyA and its metabolites), CyA, and CyA metabolites to dose/kg body weight, (t-CyA/dose, CyA/dose, and CyA-Met/dose, respectively) were significantly higher in patients with hepatitis than those in renal transplantation. In PBC patients these ratios showed a tendency to be smaller than those in renal transplantation, but were not significant. The ratio of CyA-Met/CyA was higher in the patients with hepatitis and PBC than that in renal transplantation. It was highest in the patients with PBC. The ratio of CyA Met/CyA was significantly increased with a decrease of liver functions evaluated by serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and total serum bilirubin (t-Bil). These results indicate that hepatic function affects the pharmacokinetic behavior of CyA and the increased ratio of CyA-Met/dose could be caused by a possible increased efflux of metabolites into the blood circulation due to impaired bile excretion. These results also indicate the importance of therapeutic drug monitoring (TDM) in the use of CyA with patients with hepatic dysfunction. PMID- 7883585 TI - Identification of 5' regulatory elements of the PDGF-A chain gene, and interaction with single-stranded DNA binding protein. AB - The expression of platelet-derived growth factor (PDGF) is controlled in a very complicated manner. To clarify the mechanism of regulation of the PDGF-A chain gene, deletion analysis of the 5'-flanking region was performed. We identified a positive regulatory element 25 base pairs (bp) upstream of TATAA, a negative element 135 bp upstream, a positive element 223 bp upstream and a negative element further upstream. These regulatory sites of the PDGF-A chain gene may be involved in tissue specificity, developmental regulation, and transformation. In addition, our analysis suggested the presence of a strand non-specific single stranded DNA binding nuclear protein in the positive regulatory element 25 bp upstream of TATAA. PMID- 7883586 TI - Immunolocalization of connexin 43 in the tooth germ of the neonatal rat. AB - Rabbit polyclonal antibodies to amino acids 346-360 of connexin 43, the 'heart' gap junction protein, were employed to immunolocalize connexin 43 gap junctions in the neonatal rat molar tooth germ. Connexin 43 appears early in the differentiation of both ectodermally derived and ectomesenchymally derived cells of the developing tooth. Connexin 43 immunoreactivity is present in the epithelial components of the enamel organ, including the area of the proximal and distal junctional complexes of the ameloblast layer, and the stratum intermedium, stellate reticulum and outer enamel epithelium. Secretory odontoblasts and developing alveolar bone also display a pattern of connexin 43 immunostaining. Both the epithelial and ectomesenchymally-derived components of the developing tooth acquire connexin 43 channels in a manner that correlates with cell differentiation. In addition, three regions can be defined by connexin 43 immunostaining: the epithelia of the enamel organ that are derived from the oral epithelium, the odontoblast layer derived from the ectomesenchyme, and the alveolar bone. The results suggest that connexin 43 may provide the mechanism for functional compartmentalization of the tissues associated with tooth formation. Compartmentalization suggested by connexin 43 expression could play important roles in the development and functions of these tissues. PMID- 7883587 TI - Application of biotinylated oligonucleotide probes to the detection of pituitary hormone mRNA using northern blot analysis, in situ hybridization at the light- and electron-microscope levels. AB - There have been many reports on radioisotopic in situ hybridization (ISH) studies for the demonstration of pituitary hormone mRNAs in normal pituitary gland and pituitary adenomas. Recent studies have revealed that non-radioisotopic ISH has several advantages over the radioisotopic method. Using ISH with biotinylated oligonucleotide probes, we have been able to localize various pituitary hormone mRNAs in paraffin wax or frozen sections of rat normal pituitary gland and human pituitary adenomas. For control studies we used ISH with sense probes, ISH without probes, pretreatment with ribonuclease, ISH with a probe for beta-actin and Northern blot hybridization. Using biotinylated probes, gene transcripts of rat growth hormone and prolactin were detected by Northern blot hybridization. The same biotinylated probes were used not for light microscope ISH but also for the electron microscopical demonstration of rat growth hormone and prolactin mRNAs on the polysomes of the rough endoplasmic reticula. It is emphasized that biotinylated oligonucleotide probes are useful for the analysis of pituitary endocrine function because they are applicable to the three hybridization methods, namely, Northern blot hybridization and ISH at the light and electron microscope levels. PMID- 7883588 TI - Ultracytochemical localization of particulate guanylate cyclase after stimulation with natriuretic peptides in lamb olfactory mucosa. AB - The ultracytochemical localization of particulate guanylate cyclase has been studied in lamb olfactory mucosa after activation with rat atrial natriuretic factor (rANF), porcine brain natriuretic peptide (pBNP), porcine C-type natriuretic peptide (pCNP) or rat brain natriuretic peptide (rBNP). Particulate guanylate cyclase is the receptor for these peptides and recently two subtypes of the cyclase have been identified. These isoforms are stimulated differently by ANF, BNP and CNP. Under our experimental conditions, rANF, pCNP and pBNP were strong activators of particulate guanylate cyclase in lamb olfactory mucosa, as demonstrated by the presence of reaction product. Samples incubated in basal conditions without rANF, pCNP or pBNP, or samples incubated in presence of rBNP did not reveal any cyclase activity. The rANF-stimulated cyclase activity was localized in the apical portion of olfactory epithelium. pCNP-stimulated guanylate cyclase was detected to the lamina propria in association with secretory cells of Bowman's glands and with cells in close relation with Bowman's glands (elongated cells and myoepithelial cells). The cyclase activity stimulated by pBNP was limited to cells of Bowman's glands. The present data indicate that ANF and CNP are recognized by different receptors and that BNP and CNP bind to the same receptor. PMID- 7883589 TI - Lectin binding in the anterior segment of the bovine eye. AB - Eleven different fluorescent lectin-conjugates were used to reveal the location of carbohydrate residues in frozen sections of the anterior segment of bovine eyes. The lectins were specific for the following five major carbohydrate groups: (1) glucose/mannose group (Concanavalin A (Con A)); (2) N-acetylglucosamine group (wheat germ agglutinin (WGA)); (3) galactose/N-acetylgalactosamine group (Dolichos biflorus agglutinin (DBA), Helix pomatia agglutinin (HPA), Helix aspersa agglutinin (HAA), Psophocarpus tetragonolobus agglutinin (PTA), Griffonia simplicifolia agglutinin-I-B4 (GSA-I-B4), Artocarpus integrifolia agglutinin (JAC), peanut agglutinin (PNA) and Ricinus communis agglutinin (RCA-I)); (4) L fucose group (Ulex europaeus agglutinin (UEA-I)); (5) sialic acid group (wheat germ agglutinin (WGA)). All the studied lectins except UEA-I reacted widely with different structures and the results suggest that there are distinct patterns of expression of carbohydrate residues in the anterior segment of the bovine eye. UEA-I bound only to epithelial structures. Some of the lectins reacted very intensely with apical cell surfaces of conjunctival and corneal epithelia suggesting a different glycosylation at the glycocalyx of the epithelia. Also, the binding patterns of conjunctival and corneal epithelia differed with some of the lectins: PNA and RCA-I did not bind at all, and GSA-I-B4 bound only very weakly to the epithelium of the cornea, whereas they bound to the epithelium of the conjunctiva. In addition, HPA, HAA, PNA and WGA did not bind to the corneal basement membrane, but bound to the conjunctiva and vascular basement membranes. This suggests that corneal basement membrane is somehow different from other basement membranes. Lectins with the same carbohydrate specificity (DBA, HPA, HAA and PTA) reacted with the sections almost identically, but some differences were noticed: DBA did not bind to the basement membrane of the conjunctiva and the sclera and did bind to the basement membrane of the cornea, whereas other lectins with same carbohydrate specificities reacted vice versa. Also, the binding of PTA to the trabecular meshwork was negligible, whereas other lectins with the same carbohydrate specificities reacted with the trabecular meshwork. GSA-I-B4 reacted avidly with the endothelium of blood vessels and did not bind to the stroma, so that it made blood vessels very prominent and it might be used as an endothelial marker. This lectin also reacted avidly with the corneal endothelium. Therefore, GSA-I-B4 appears to be a specific marker in bovine tissues for both blood vessel and corneal endothelium cells. PMID- 7883591 TI - Intratracheally-instilled antileukoprotease and alpha 1-proteinase inhibitor: effect on human neutrophil elastase-induced experimental emphysema and pulmonary localization. AB - The protective capacities of intratracheally-instilled antileukoprotease and alpha 1-proteinase inhibitor towards human neutrophil elastase (HNE)-induced pulmonary injuries were compared in hamsters. The antiproteases were instilled in equimolar amounts up to 20 h before HNE instillation. At all intervals, both inhibitors were able to inhibit HNE-induced emphysema efficiently. At 1 h before HNE instillation, alpha 1-proteinase inhibitor was more effective in this regard than antileukoprotease. alpha 1-Proteinase inhibitor, instilled 1 to 12 h before HNE, efficiently inhibited HNE-induced haemorrhage, while the antileukoprotease protected haemorrhage only when it was administered 1 h before HNE. The development of secretory cell metaplasia was affected only when both inhibitors were instilled 1 h before HNE. In a second series of experiments, the localization of the two antiproteases after intratracheal instillation in hamster was investigated using an indirect immunofluorescence technique. Up to 20 h after installation, antileukoprotease was found to be associated with elastin fibres at all points of time investigated. In contrast, alpha 1-proteinase inhibitor was observed to be located in the alveolar lining and diffusely in the alveolar lung tissue at all points of time investigated. No association of the inhibitor with elastin fibres was found. We conclude that the fraction of antileukoprotease associated with the elastic fibre may be important in the protection of HNE induced pulmonary emphysema. PMID- 7883590 TI - Two-dimensional cryostat section electrophoresis: a novel method and its application to the diseased synovial membrane. AB - A two-dimensional electrophoresis technique for analysing sections of human tissue is described. Cryostat sections, 10 microns thick, are placed on an isoelectric focusing gel and then transferred to an SDS gel in the second dimension. The protein pattern is visualized by silver staining and is thought to represent soluble proteins. The silver-stained proteins were found to be both reproducible and, to the extent tested, organ-specific. This method was used to analyse 43 synovial membranes from patients suffering from rheumatoid arthritis or degenerative joint diseases. The analysis did not reveal any specific protein pattern for rheumatoid arthritis. The protein spot number was not related to the cause of arthritis. However, the total protein spot number was related to the histomorphological synovitis type, with those exhibiting either an exudative or proliferative synovitis pattern possessing significantly higher protein spot numbers than those specimens exhibiting a sero-fibrous or lympho-plasmacytic pattern of synovitis. PMID- 7883592 TI - Major histocompatibility complex class II alleles and haplotypes and blood groups of four Amerindian tribes of northern Colombia. AB - MHC class II alleles and haplotypes were determined from unrelated individuals and families of the Arhuaco (n = 107), Kogi (n = 42), Arsario (n = 18), and Wayu (n = 88) tribes located in the northern part of Colombia. Class II DRB, DQA1, and DQB1 alleles were determined by PCR-SSO and PCR-RFLP based methods. Four haplotypes, [DRB1*0407, DRB4*0101, DQA1*03, DQB1*0302]; [DRB1*0403, DRB4*0101, DQA1*03, DQB1*0302]; [DRB1*1402/1406, DRB3*0101, DQA1*0501, DQB1*0301]; and [DRB1*0802, DQA1*0401, DQB1*0402], were observed among these four tribes. In addition to these haplotypes, the Wayu Indians showed a frequency of 21.3% for the [DRB1*1602, DRB5*02, DQA1*0501, DQB1*0301] haplotype, 13.1% for the [DRB1*0411, DRB4*0101, DQA1*03, DQB1*0302] haplotype, and 8.1% for the [DRB1*0411, DRB4*0101, DQA1*03, DQB1*0402] haplotype. Red cell antigen typing was used to calculate genetic admixture. The Kogi and Arsario showed no genetic admixture while the Arhuaco tribe showed admixture with genes of African origin and the Wayu showed admixture with Caucasians as well as genes of African origin. These findings were confirmed by the MHC class II allele and haplotype data obtained, as alleles and haplotypes of Caucasian and African origin were detected in the Wayu and Arhuaco and not in the Kogi or Arsario. These studies will be important in disease association and transplantation studies for Amerindian and colombian populations and for correlating genetic traits with the anthropologic and linguistic data available in order to better understand the Amerindian populations. PMID- 7883593 TI - Tumor necrosis factor alpha-308 gene variants in relation to major histocompatibility complex alleles and Felty's syndrome. AB - The location of the human TNF genes within the MHC complex has prompted much speculation about the role of TNF alleles in the etiology of MHC-associated autoimmune diseases. On sequencing the 5' regulatory region of the human TNFA gene a G (TNFA-308G) to A (TNFA-308A) transition polymorphism at position -308 was discovered. We have developed a simple PCR assay to facilitate the screening of the -308 polymorphism at the DNA level. In view of the possible linkage between the TNFA-308A allele and a certain MHC type, TNFA-308 genotypes in HLA typed healthy individuals (n = 88) were determined. A statistically significant association between the TNFA-308A allele and HLA-DR3, DQB1*0201, DQA1*0501, A1, B8, and the NcoI 5.5-kb RFLP of the TNFB gene was observed. In addition, we determined the frequency of the TNFA-308A allele in patients with FS (n = 13), an HLA-DR4-associated disease. In this study, no association was found of Felty's syndrome with the TNFA-308A allele, indicating that this allele does not appear to be a susceptibility factor for FS. PMID- 7883594 TI - Characterization of the HLA-A polymorphism by locus-specific polymerase chain reaction amplification and oligonucleotide hybridization. AB - This report describes a PCR-based typing protocol for the HLA-A polymorphism. Locus-specific primers selectively amplified HLA-A sequences from exon 1 to exon 3 in a single PCR that avoided co-amplification of other classical and nonclassical class I genes. The allelic variation in exons 2 and 3 of the HLA-A gene was examined with a set of 44 oligonucleotide probes. According to the recognized HLA-A sequences the protocol is potentially able to distinguish all known HLA-A alleles with unique nucleotide sequences in this gene region. The related HLA-A genotypes can also be identified in both homozygous and heterozygous individuals. Thus the protocol provides the highest resolution for HLA-A typing. The PCR-SSO typing technique is accurate, reliable, and particularly suitable for a large number of samples. The DNA typing results from 42 Tenth IHWS B-cell lines are compatible with the serologic and IEF definitions. Sixty-six unrelated donors from a northern Chinese population were also tested, with 16 HLA-A alleles detected. Four subtypes of HLA-A2 were found in this population. The distribution of HLA-A subtypes in the population indicated that 40% of donor-recipient pairs thought to be matched for HLA-A by serology would be mismatched. Two novel HLA-A alleles were identified by unusual oligonucleotide hybridization patterns. PMID- 7883595 TI - Association between chronic cutaneous lupus erythematosus and HLA class II alleles. AB - CCLE, a disease entity at the benign end of the lupus spectrum, is characterized by marked photosensitivity and skin lesions in sun-exposed areas. The histopathology of lesions resembles hypersensitivity type IV reactions. We have asked whether an association between class II alleles and CCLE exists. RFLP analysis of HLA-DQA genes revealed a Taq I HLA-DQA1 allelic restriction fragment overrepresented in a group consisting of 26 patients as compared to healthy control individuals. This result was corroborated by typing with oligonucleotide probes. The presence of the DQA1*0102 allele in the patients' group led to a relative risk of 4.57, with a statistical significance of p < 0.05 after correction for 36 comparisons. Although not statistically significant, it is interesting that all patients possess in at least one of their HLA-DQA1 alleles a nucleotide sequence coding for the amino acid glutamine at position 34 of the DQ alpha molecule. The expected frequency of these alleles in the control population amounts to 82%. The HLA-DRB1*16 allele, which is found in linkage disequilibrium with the HLA-DQA1*0102 allele, is also observed at an increased frequency in the patient's group, though the association was not significant after correction for the number of comparisons. However, no associations of CCLE with alleles at the HLA-DPB1 locus was found. The association of CCLE with certain HLA class II alleles points to an involvement of HLA-DQ and/or -DR molecules in the pathogenesis of the disease. Alternatively, genetic loci in linkage disequilibrium may code for elements which contribute to the development of CCLE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883596 TI - T cells from the small intestinal mucosa of a DR4, DQ7/DR4, DQ8 celiac disease patient preferentially recognize gliadin when presented by DQ8. AB - CD is an immunologic disease of the small intestine which is precipitated by ingestion of wheat gliadin. Most patients carry the HLA-DQ (alpha 1*0501, beta 1*0201) (DQ2) heterodimer. We recently reported that a preponderance of gliadin specific T cells from the small intestinal mucosa of DQ2-positive CD patients were restricted by this DQ heterodimer. However, a small percentage of CD patients do not carry this DQ heterodimer, and most of them instead carry DQ (alpha 1*0301, beta 1*0302) (DQ8). Here we report that a majority of gliadin specific T cells from the small intestinal mucosa of a DR4,DQ7/DR4,DQ8 heterozygous CD patient are restricted by DQ8. Thus, preferential presentation of gliadin-derived peptides to T cells by the CD-associated DQ2 and DQ8 molecules may be an initial and important immunopathogenic step in CD. PMID- 7883597 TI - Toward an understanding of the health status of black adolescents: an application of the stress-coping framework. AB - The transition from adolescence to adulthood for many urban black youth today contains a number of formidable barriers and often results in a variety of adverse developmental and behavioral outcomes. Nurses and other health providers have an obligation to answer the urgent need for improvements in the health status of black adolescents. This paper reviews the current psychosocial functioning of black youth while emphasizing the disadvantaged social contexts in which most live, which place them at a higher risk for a variety of negative outcomes. Data concerning mental and social health indicators for black adolescents suggest (a) a negative mental health trajectory with high rates of depression, psychiatric hospitalization rates, and suicides, and (b) a poor social health status with alarming school dropout and juvenile delinquency rates, and chronic violence exposure, substance use, and teen pregnancy. An application of the stress-coping framework to black adolescents is suggested as a way to conceptualize the relationship between stress factors and their influence on development. Because this framework places much emphasis on environmental factors as causes for psychological distress, it provides a means to account for the differential incidence of mental and social illnesses among black adolescents. Nursing interventions related to stress and coping among black adolescents may serve to increase well-being and actualize health promotion. However, research efforts are needed to discover which strategies are used by black youth to cope with the stressful experiences faced in their daily lives. Findings could enhance the design, planning, and implementation of prevention and educational programs, making them more consistent with the unique needs of black adolescents. PMID- 7883598 TI - Anticipatory guidance: alcohol, adolescents, and recognizing abuse and dependence. AB - Alcohol is the most used and abused addictive drug used by adolescents, making adolescent alcohol abuse a major social problem. Alcohol-related traffic fatalities continue to be the leading cause of death for 15-19-year-old youths. Factors that influence adolescents' decision to drink and drive include lack of reliable knowledge about alcohol and its effects, and lack of decision-making skills. Literature shows that promoting public awareness and education is a major method of prevention of alcohol abuse in its early stages. Nursing's goal is to help families to have a greater degree of intrafamily control and coping. Anticipatory guidance is an excellent method of empowering and educating families about alcohol facts, including risk factors, phases and consequences of usage, problem identification via information probes, and interventions that can be instituted early in a child's life to prevent adolescent alcohol-related problems. PMID- 7883599 TI - Health behaviors of adolescents who have been diagnosed with cancer. AB - Many challenges related to the development and diagnosis of cancer are faced by adolescents with the disease. Adolescence is a developmental period for behaviors that risk health. The article describes behaviors that promote and risk health among adolescents who have been diagnosed with cancer. A paucity of studies exists on health-promoting and -risking behaviors among adolescents with cancer. Further studies are needed to explore and describe these adolescents' health promoting and -risking behaviors. Health care professionals must comprehensively address these adolescents' health care needs related to the diagnosis of cancer as well as the developmental challenges of adolescence. PMID- 7883600 TI - Coordinating a multidisciplinary discharge for the technology-dependent child based on parental needs. AB - Primary nurses, case managers, and clinical nurse specialists in pediatric settings are continually providing care for chronically ill children. With our advancing medical knowledge and technology, the concept of chronically ill children has taken on an added dimension: technology-assisted living. Technology dependent children pose the greatest challenge for discharge into the home environment. This article identifies the chronically ill technology-dependent child and family and their needs in order to develop a chronologic plan for a successful multidisciplinary discharge. PMID- 7883601 TI - Graduate nursing education: developmental disabilities and special health care needs. AB - As children and adults with developmental disabilities and special health care needs are integrated into home, school, and community life, nurses are being required to provide leadership, advocacy, and training in community settings to a much greater extent than in the past. To assess the school and community need for formal graduate preparation for nurses who work with individuals with developmental disabilities and/or special health care needs, 25 nurses in leadership positions representing urban and rural health agencies throughout Minnesota took part in a 5-hour focus group discussion. Analysis of data summarized from this process shows five features of the recommended curriculum necessary for advanced practitioners in this specialty area: (a) discipline specific core competencies, (b) discipline-specific specialty competencies, (c) genetic competencies not specific to nursing but necessary to function in nursing roles, (d) interdisciplinary and intradisciplinary learning experiences, and (e) clinical experiences with preceptors. The authors recommend the development of interdisciplinary graduate programs designed to prepare nurses to assume leadership roles in school health, public health, home health care, and systems management that will affect public policy and, ultimately, promote change in the systems charged with responsibility to serve this population. PMID- 7883602 TI - Take me out to the ball game: growing up female in America. PMID- 7883603 TI - The nurse's role in planning for inclusion of medically fragile and technology dependent children in public school settings. AB - With the increasing number of medically fragile and technology-dependent children in schools, greater collaboration is required between health care professionals and public school personnel to ensure that safe and effective services are provided. This article describes a comprehensive process involving two different, though interrelated, teams on which the pediatric nurse plays a critical role. The process involves collaborative multidisciplinary medical-health team activities, referral to the educational system before discharge from the hospital setting, collaborative multidisciplinary medical-health-educational team activities, and development of a health care plan, training, and follow-up that facilitates a safe, successful transition from the medical-rehabilitation setting into the community educational environment. Implications for states are provided, with special emphasis on rural communities. PMID- 7883604 TI - Statistical power analysis in pediatric nursing research. AB - Pediatric nurse researchers take a serious risk when they design an intervention study with insufficient power. In an underpowered study, the researcher may be testing a genuinely effective treatment but fail to recognize its efficacy. In the first part of this article, the concept of power analysis and how to perform a statistical power analysis are addressed. The second half of this article includes a review of published nursing research studies for the past 5 years in three nursing research journals. Specific examples of pediatric nursing research are highlighted. This review revealed a neglect of power analysis. Nurse researchers need to pay greater attention to statistical power analysis. It is an essential procedure for researchers to use before conducting a study. PMID- 7883605 TI - Effect of parental participation on hospitalized child behavior. AB - A short-term longitudinal descriptive evaluation of current levels of parents' participation in the care of a child hospitalized with leukemia was conducted to identify varying levels of parent participation and their relationship to the child's behavior during hospitalization. A positive relationship between the number of activities a parent participates in and the child's behavior during hospitalization was revealed. PMID- 7883606 TI - Who's moving the children? Pediatric transport: selection, education, and management. AB - Moving patients through the maze of available services within the health care system is, at best, complex. When the patient is a child and that child is seriously ill, the situation progresses from complex to critical. The expeditious and safe transport of a seriously ill child is generally assigned to a specifically designated and trained group of health care professionals. Although such transport is essential, only a few sources could be found in the literature that described the role preparation, function, or management of a pediatric transport team. Therefore, this study was undertaken to collect information from institutions that provide transport services for neonatal and pediatric patients. The purpose was to identify national trends, describe the composition and functional aspects of the transport team, and identify criteria used for selection, orientation, and training of team members. Representatives of 56 geographical and administratively diverse institutions responded to a structured telephone interview. Findings revealed two functionally distinct types of transport teams: dedicated (N = 38) and unit based (N = 18). Included in the data obtained were types and numbers of patients transported, average response time and distance, personnel composition, and educational and experiential standards for staff and management. PMID- 7883607 TI - William Malcolm Beeson, 1911-1988: a brief biography. PMID- 7883608 TI - Influence of penning type and feeding level on sexual behavior and feet and leg soundness in boars. AB - Ninety-six Yorkshire males at 28 d of age were placed on a pre-test feeding regimen (22% CP) of either ad libitum (A) access to feed or a restricted (R, 85% of A) diet. All pigs were housed in groups of four until approximately 30 kg body weight. The boars were then placed under test and assigned to a group pen (GP) containing eight boards or to individual pens (IP) and fed a 16% CP diet at A or R levels. Feeding types during pre-test and test phases were, therefore, ad libitum followed by ad libitum (AA), ad libitum: restricted (AR), restricted: ad libitum (RA), and restricted: restricted (RR) for each of the two (IP and GP) housing types. All boars were weighed every 2 wk to determine the feeding level and ADG. The pen floors were partly slatted with water nipples in the slatted areas. Areas available for each board were 1.63 and 2.15 m2 in IP and GP, respectively. Sexual behavior, semen characteristics, and feet and leg scores were recorded between 150 and 240 d of age. The IP boards required longer (P < .05) contact with receptive gilts before mating, made more (P < .01) ano-genital sniffings, and attempted more (P < .10) incorrect mounts than GP boars. The GP boards had a higher (P < .01) mating score, younger (P < .001) age at completion of the mating test, and lower (P < .01) total sperm count and sperm concentration (P < .001) than IP boars. The AA boards exhibited less (P < .10) chomping and salivation than boars on other feeding regimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883609 TI - Comparison of litter adjustment factors in Yorkshire and Landrace data. AB - National Swine Improvement Federation (NSIF) adjustment factors presently used to standardize litter data for age at 21 d, number born alive (NBA), 21-d litter weight, and number after transfer (NAT) were evaluated using 104,884 litters in 1,348 Yorkshire herds and 20,370 litters in 197 Landrace herds. In addition, adjustment factors for number weaned were calculated for standardization of this trait. Number weaned is adjusted for parity and NAT. The mixed-model least squares, maximum likelihood computer program described by Harvey was used in the analyses. Yorkshire and Landrace data were combined to test for breed effects and interactions involving breed. Breed interactions were different (P < .05). Therefore, breed-specific adjustment factors were calculated for Yorkshire and Landrace data sets. Also, adjustment factors were calculated for combined data that might be appropriate to use for breeds without specific adjustments available. Parity adjustment factors for NBA and 21-d litter weight were different (P < .05) from current NSIF recommendations, as was the NAT adjustment for 21-d litter weight. The age-at-weaning multiplicative factors were not different (P > .05) from current NSIF values. However, in all three data sets, the intercepts and linear coefficients of the quadratic regression for age at weaning were different (P < .05) from NSIF's. A Student-Newman-Keuls (SNK) test was used to evaluate the NSIF groupings of parity and number after transfer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883610 TI - Performance, clinical chemistry, and carcass responses of finishing lambs to formulated sometribove (methionyl bovine somatotropin). AB - Formulated zinc methionyl bST (sometribove, 50, 100, or 150 mg) was administered as a single treatment once every 2 wk or as two equal treatments once/week to evaluate the efficacy of prolonged release delivery of bovine somatotropin (bST) in finishing lambs. Feed conversion during the 6-wk treatment period was improved 9 and 19% in lambs that received treatments once and twice/2 wk, respectively (P < .05), and the responses to differing doses were similar within a dosing frequency (P > .05). Carcass muscle:fat ratio indicators generally were affected in a dose-related manner and were independent of frequency of administration. For example, fat thickness was 17, 30, and 42% lower than control in lambs that received 50, 100, and 150 mg of formulated sometribove/2 wk, respectively (P < .05). Percentages of muscle were higher and of fat were lower with increasing dose of formulated sometribove, but weight of only fat was significantly affected (P < .05). Clinical chemistry indices of metabolic effects of bST (e.g., circulating bST, IGF-I, insulin, glucose, and urinary nitrogen concentrations) were affected in directions similar to those observed with bST administered by daily injection. The results of this study demonstrate the growth performance and carcass composition advantages of a formulation designed to deliver bST over a 2 wk period. PMID- 7883611 TI - Transport of pigs different with respect to the halothane gene: stress assessment. AB - Two transport experiments were carried out with 18 pigs each. These pigs originated from three genetic lines (homozygous halothane-positive and -negative and heterozygotes). Half the pigs were unfed for 12 h before transport. All pigs were transported twice for 2 h. Before and after transport pigs were anesthetized to take blood samples from the jugular vein and biopsies from the biceps femoris. At the same time equipment to measure body temperature and heart rate were attached or detached. Plasma cortisol and beta-endorphin concentrations were measured as well as the glycogen concentration in the muscle sample. Line differences were detected with respect to body temperature (P < .04), heart rate (P < .05), and cortisol (P < .01). The withholding of feed influenced (P < .04) plasma beta-endorphin concentration. Body temperature (P < .02), heart rate (P < .001), cortisol (P < .01), and beta-endorphin (P < .001) were different before and after transport, whereas a training effect of the transport number was observed for heart rate (P < .07) and plasma beta-endorphin (P < .02). No interactions between treatments were observed. The relationship between cortisol and beta-endorphin suggests a nonconcomitant release of ACTH and beta-endorphin. PMID- 7883612 TI - Additive genetic groups for animals evaluated in more than one breed association national cattle evaluation. AB - Additive genetic groups were included in the 1993 Red Angus Association of America national cattle evaluation for phantom parents of individuals who were registered with the American Angus Association (AAA). Genetic groups were formed for each component in two multiple-trait evaluations in which all animal effects were fit. Additive direct effects were included for birth weight, weaning weight (WW), and milk (MILK). In a second analysis the additive direct effect of 160-d postweaning gain was analyzed with WW and MILK. Of the 387,665 animals, 50,838 had at least one phantom parent assigned to one of five genetic groups fit as fixed effects for each additive component. Of these 50,838 animals, 1,324 were identified as registered with the AAA. An average of 906 animals per component had an AAA EPD available. Animals with a known AAA EPD were designated into one of three groups of equal numbers based on AAA EPD for each component (1 = low, 2 = medium, 3 = high). Animals in the fourth genetic group were those registered with the AAA but with no EPD available for the component. The fifth genetic group included all other animals with phantom parents. Grouping on AAA EPD allowed for EPD on animals out of parent(s) registered with the AAA to be more closely aligned to the AAA EPD because they were regressed from the group solution instead of zero. Grouping based on EPD from another NCE should be considered in the production of multibreed EPD. PMID- 7883613 TI - Effects of data structure on variance of prediction error and accuracy of genetic evaluation. AB - Several features of data structure were studied to determine their effects on variance of prediction error and accuracy of evaluation. Assigning 50 sires with progeny to a portion of 10, 25, or 50 contemporary groups according to a sire model with and without additive genetic relationships, or assigning 50 individuals with their own record to one of 2, 5, or 10 contemporary groups according to an animal model, established the designs. Additive genetic relationships were based on stimulated pedigree files. Low, medium, and high heritabilities (.10, .25, and .40, respectively) were considered. The inverse of coefficient matrices gave variances of prediction error. Populations derived from the sire model (n = 8,100) consisted solely of progeny-tested individuals. For them, number of progeny had a quadratic (P < .001) association with variance of prediction error (R2 = 56 to 82%), which selection index theory underestimated when there were < 100 progeny. Number of direct connections (sires of contemporaries of progeny) together with progeny numbers explained variance of prediction error (R2 = 76 to 90%) better than either variable alone. With no direct connections, variance of prediction error was maximum unless a relative with at least one direct connection itself existed. Populations derived from the animal model (n = 900) consisted of animals with designs representing a progeny test, performance test, or a combination of both (34, 41, and 25% of the total, respectively). For performance-tested animals (without progeny), number of genetic connections was not highly correlated with variance of prediction error (r = -.10, across h2), but relatives prevented zero accuracies when contemporary groups consisted of one animal. Even when animals had no relatives, more than five members per contemporary group gave little additional increase in accuracy. For other than a progeny test, designs were complex, being described by many variables that were confounded. PMID- 7883614 TI - An experimental comparison of equivalent terminal and rotational crossbreeding systems in swine: pig performance. AB - Eleven thousand forty-nine pigs produced from 934 litters using 262 rotational and F1 crossbred sows were used to study differences in pig weights, survival rates and pen average daily gain, daily feed intake, and feed conversion between pigs from equivalent three-breed rotational and three-breed terminal crossbreeding systems using Duroc, Yorkshire, and Landrace breeds. Pig weights at birth and 21 and 56 d and days to reach 100 kg did not differ (P > .10) between the terminal and rotational crossbreeding systems. However, ultrasound backfat thickness of pigs from the terminal crossbreeding system was .04 cm greater (P < .007) than that of pigs from the rotational crossbreeding system. Survival rate from 56 d to 100 kg was .8% greater (P < .01) for pigs from the terminal crossbreeding system than for those from the rotational crossbreeding system. The crossbreeding system had no effect (P > .10) on survival rate at birth, from birth to 21 d, from 21 to 56 d, or from birth to 100 kg. Differences between the two crossbreeding systems were nonsignificant (P > .20) for pen average daily gain, daily feed intake, and feed conversion. Breed composition of pigs was an important source of variation (P < .01) for pig weights at birth and at 56 d. Similarly, breed composition of the pig also affected ultrasound backfat thickness at 100 kg (P < .01), but not days required to reach 100 kg (P > .10). For survival traits, only survival rate from 56 d to 100 kg was influenced by breed composition of the pig.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883615 TI - Life cycle evaluation of five biological types of beef cattle in a cow-calf range production system: I. Model development. AB - Data collected during a 10-yr study at the Northern Agricultural Research Center (NARC), Havre, MT were used in construction of a simulation model to evaluate production systems using different breed groups. Five dam breed groups, straightbred Hereford (HH), 50% Angus-50% Hereford (AH), 25% Simmental-75% Hereford (1S3H), 50% Simmental-50% Hereford (1S1H), and 75% Simmental-25% Hereford (3S1H), were studied. The simulated system was a northern range cow-calf production system with spring calving and fall weaning. Replacement heifers were purchased and all calves were marketed at weaning. All nonpregnant females were sold in the fall. Statistical analyses of the data yielded input values (least squares means for breed group x age x sex subclasses) for cow and calf weights, pregnancy rate, dystocia, and calf survival. Pregnancy, dystocia, calf survival, calf weights, and cow weights were simulated stochastically. Energy requirements for maintenance, growth, gestation, and lactation were predicted from equations adapted from the literature based on body weight, frame size, sex, and breed group. Economic inputs and outputs were computed by accounting for variable input expenses and output revenues associated with animal performance and fixed costs associated with range management. Simulated measures of system performance included measures of energy conversion, break-even prices, and profit. PMID- 7883616 TI - Life cycle evaluation of five biological types of beef cattle in a cow-calf range production system: II. Biological and economic performance. AB - Results from a 10-yr study of five dam breed groups in a range beef production system were used as inputs to a simulation model to evaluate life cycle biological and economic performance. Dam breed groups were straightbred Herefords (HH), Angus-Hereford and Simmental-Hereford F1 crosses (AH and 1S1H), 75% Hereford-25% Simmental (1S3H), and 25% Hereford-75%. Simmental (3S1H). Biological measures were number of lifetime matings, calves weaned and kilograms of calf weight sold per cow exposed, and metabolizable energy (ME) consumed per kilogram of calf weight sold and per kilogram of total weight sold. Simulated economic measures were break-even steer prices, total production costs, net profit per cow exposed, and net profit for a ranch of fixed size. The HH and 3S1H dams consumed the least ME per kilogram of total weight sold yet had the highest steer break even prices and lowest profits. The F1 dams yielded consistently higher profits than other dam breed groups. Breed group rankings were not sensitive to prices paid for hay or calf prices relative to cow prices. Regression techniques were used to estimate maternal heterosis and maternal breed substitution effects from the simulated data. Maternal heterosis effects were large and highly significant for all measures of system performance and were desirable for all traits except ME/kilogram of total weight sold. Maternal heterosis for net profit was nearly $70.cow-1.yr-1 and $20,400/yr for a ranch of fixed size (2,700 AUM range forage). Maternal breed substitution effects were generally much smaller than heterosis effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883617 TI - Heat and social stress effects on pig immune measures. AB - Forty-eight domestic pigs were used to evaluate the effects of heat and social stress on immune indices. Pigs were brought together in groups of three per pen and video-taped for the first 72 h. Video tapes were viewed to determine time spent in aggressive and submissive behaviors. Social status of each pig was determined from outcomes of agonistic interactions. Pens of pigs were housed in either a thermoneural (control, 24 degrees C) or heat-stress (33 degrees C) air temperature. Immune measures were determined from blood samples obtained on d 0, 7, 14, 21, and 28 after grouping. Social status had an effect (P < .05) on lymphocyte proliferation in response to pokeweed mitogen: socially intermediate pigs had a higher proliferative response than socially dominant or subordinate pigs. Many immune measures showed a significant interaction between heat and social stress over days of the study. Generally, socially dominant or submissive pigs had alterations in immune function (elevated numbers of neutrophils, decreased antibody production) compared with socially intermediate pigs. In conclusion, heat and social stress interact in their effect on the pig's immune system. Although one might have predicted immunosuppression among submissive pigs, there also seemed to be immunological costs to dominant pigs as well. These data also have implications in design of stressor research in that social behavior should be measured or controlled. PMID- 7883618 TI - An ellipsoid farrowing crate: its ergonomical design and effects on pig productivity. AB - An ellipsoid farrowing crate was designed and compared to the conventional rectangular crate with regard to its effect on sows' production traits. The main features of this crate are its oval horizontal frame and bowed vertical bars. Thirty-two sows farrowed in each system. Those in the ellipsoid crates raised 318 pigs and those in the rectangular crates raised 304. Stillbirth rate was lower in the ellipsoid crates than in the rectangular crates (P < .05). Among pigs born live, no significant difference due to crate was found on the deaths by crushing, infection, and other causes. The overall pigs' weaning rate from total births was also similar in both crates (P > .05). The daily weight gains of pigs for the 1st wk in the ellipsoid crate did not differ from those of pigs in the rectangular crates (P > .05) but were higher for the period from d 7 to d 21 (P < .05). The ellipsoid crate allowed the sow to turn around and have more freedom to move. However, the increase in sow movement did not cause a higher pig crushing rate than that in the traditional crate (P > .05). Behavioral observations also showed that the ellipsoid farrowing crate permitted easier visual and tactile contact of dams with their pigs and offered pigs better access to the sow's teats. PMID- 7883619 TI - The mechanical properties of equine third metacarpals as affected by age. AB - Twenty-five pairs of equine third metacarpals (McIII) were collected from horses of varying breeds and ranging in age from 1 d to 27 yr. Standard three-point bending tests were performed on the McIII to obtain comparative data on breaking load (BL), breaking strength (BS), and elasticity (E). Broken bones were reassembled and 2-cm sections cut from the bone 1 cm below the nutrient foramen and at the site of the break. Bone mineral content (BMC) and geometrical properties of these sections were determined. Maximum BMC (17.3 g/2 cm) was reached at 6.0 +/- 1.8 yr of age. Horses in this study achieved 76% of maximum BMC by 1 yr of age. Maximum BL (1,888 kg) was reached at 4.6 +/- 1.8 yr of age. The coefficient of determination (r2) between BMC and BL was .92 (P < .001). Breaking strength peaked at 2,272 kg/cm2 at 6.3 +/- 1.2 yr of age. The correlation between BS and BMC was .84 (P < .0001). At 1 yr of age BS was 1,919 kg/cm2, or 85% of maximum BS. Elasticity increased linearly with log 10 age (r2 = .91). The r2 of BMC and E was .79 (P < .001). Area moment of inertia (I) of the cortex of the bone was best approximated by the area of an ellipse (r2 = .91; P < .01). Results suggest that bone strength in horses peaks after most race horses have completed their careers. PMID- 7883620 TI - Stearoyl coenzyme A desaturase enzyme activity and mRNA levels are not different in subcutaneous adipose tissue from Angus and American Wagyu steers. AB - We proposed that greater stearoyl coenzyme A (CoA) desaturase enzyme activity caused the elevated monounsaturated fatty acids observed in American Wagyu adipose tissue. Stearoyl CoA desaturase mRNA concentrations and enzyme activities were measured in subcutaneous adipose samples from Angus (n = 5) and American Wagyu (n = 5), fed to the Japanese market end point. A rat liver stearoyl CoA desaturase cDNA clone was used to measure the relative amounts of stearoyl CoA desaturase mRNA. Enzyme activities and mRNA concentrations, as measured by laser densitometry of slot-blot autoradiograms, were not significantly different between the two breeds at this stage of growth. This investigation has demonstrated that, at this stage of maturity, differences in fatty acid composition between Angus and American Wagyu steers cannot be attributed to differences in stearoyl CoA desaturase enzyme activity. PMID- 7883621 TI - Effects of testosterone on skeletal growth in lambs as assessed by labeling index of chondrocytes in the metacarpal bone growth plate. AB - The effects of testosterone on the epiphyseal growth plate of metacarpal bones of growing sheep were evaluated in 20 rams, 20 wethers, and 20 wethers receiving subcutaneous testosterone replacement therapy. Two animals from each testosterone treatment group were slaughtered at 14-d intervals from 49 to 133 d, and then at 28-d intervals until 217 d, for a total of 10 slaughter ages. Immediately after slaughter, the cannon bones were dissected of extraneous tissue, weighed, and their lengths measured. Growth plates from the metacarpal bones were isolated and explants were cultured for 24 h in medium containing [3H]thymidine. After autoradiography, labeling index was calculated as the ratio of labeled to total nuclei in the resting and proliferative zones of the growth plate. Testosterone increased (P < .03) weight and length of the metacarpal bone. Increased bone length due to testosterone was associated, in part, with a higher (P < .05) labeling index in chondrocytes of the proliferative zone of the growth plate. Labeling indices in the resting zone chondrocytes of rams were higher near the time of puberty. Accelerated growth followed by cessation of growth occurs concurrently with puberty in males of several species and is accompanied by an increase in the blood concentration of testosterone. Testosterone may mediate this accelerated growth by first increasing bone growth and then depleting the source of stem cells in the cartilage growth plate, the site where growth in length of long bones occurs. PMID- 7883623 TI - Electromagnetic scanning of pork carcasses in an on-line industrial configuration. AB - The objective of this study was to test and validate electromagnetic scanning of whole pork carcasses in an on-line, integrated, industrial configuration. The electromagnetic (EM) scanner was installed in two pork processing facilities (Plant A and Plant B). Plant A was a small pork fabrication plant that further processed chilled pork carcasses. Carcasses were delivered to Plant A by refrigerated trucks. The amount of EM energy absorbed by the carcasses was recorded as they were conveyed through the EM field. A plot of the absorption units over time (EM scan curve) was used to obtain predictive variables for estimating carcass and primal cut composition. Forty-eight whole, chilled carcasses (Group A) were electromagnetically scanned and conveyed onto the fabrication line. The average percentage carcass lean for Group A was 49.1% (range = 36.5 to 59.5%). Right carcass sides were removed from the processing line, fabricated into primal cuts, and dissected into fat, lean, and bone. Prediction equations were developed from EM scans for weight of total dissected carcass lean (R2 = .830; root mean square error = 1.80 kg), percentage of carcass lean (R2 = .820; root mean square error = 2.29%), and weight of dissected ham, longissimus muscle, and shoulder lean. In Plant B, the electromagnetic scanner was installed at the end of a pork slaughter line to ensure carcass scanning at a consistent carcass temperature. Fifty whole, pre-rigor eviscerated carcasses (Group B) were electromagnetically scanned before entering the chill cooler where fat and loin tissue depths were obtained by an optical grading probe. The average percentage carcass lean for Group B was 46.7% (range = 30.1 to 57.3%). Prediction equations were developed from EM scans for weight of total dissected carcass lean (R2 = .904; root mean square error = 1.59 kg), percentage of carcass lean (R2 = .863; root mean square error = 2.05%), and weight of dissected ham, loin, and shoulder lean. Statistical equations developed for the prediction of dissected primal cut lean were superior from EM scans of Group B (prerigor) carcasses. Electromagnetic scanning proved more statistically efficient than optical probes for predicting weight of dissected carcass lean and percentage of carcass lean. Statistical comparison of EM scan equations from Groups A and B are not completely valid because two different populations of carcasses were tested at different times of the year. The results of this study show that EM scanning has the potential to accurately predict pork carcass composition in a fully automated, on-line industrial configuration. PMID- 7883622 TI - Carcass composition of "bob" and "special-fed" veal and its prediction. AB - Percentage of lean, fat, and bone were determined in 18 bob veal (BV) and 28 special-fed veal (SFV) carcasses. Carcasses were subjected to a set of visual conformation scores and a variety of physical measurements. No significant differences were found regarding carcass percentage of lean, fat, and bone within the three BV weight groups (P > .05). On average, SFV were 12% fatter than BV and did not have a greater percentage of lean (P > .05), except for SFV carcasses weighing 88.2 to 97.7 kg. Bob veal had less fat (internal, external, and intermuscular) and a higher bone percentage than SFV (P < .05). The round and shoulder primals had the greatest proportion of lean in both the BV and SFV carcasses. Bob veal carcasses had an average conformation score of average Good and SFV carcasses had an average conformation score of average Choice. In addition, a parsimonious subset of variables was identified for predicting total percentage of lean (TPLEAN) for both BV and SFV separately, using "stepwise" regression model building procedures. For BV, all four identified predictor variables were subjective conformation scores (i.e., muscling, appearance, leg thickness, loin-back plumpness) (R = .73, P < .03). For SFV, four predictor variables were also identified: kidney and pelvic fat, fat thickness, carcass length, and lateral thickness (R = .61, P < .03). Although both regression equations were significant predictors of TPLEAN, confidence limits for predicting future TPLEAN value were wide relative to the variation in the actual TPLEAN values. Thus, the practical utility of the regression equations is limited. PMID- 7883624 TI - Biological availability of phosphorus in defluorinated phosphates with different phosphorus solubilities in neutral ammonium citrate for chicks and pigs. AB - Two experiments were conducted to assess the bioavailability of P in five sources of defluorinated phosphate (DFP) that differed in P solubility in neutral ammonium citrate (NAC). In Exp. 1, 384 2-d-old male chicks were fed a corn cornstarch-dextrose-soybean meal basal diet (1.22% lysine, 1.00% Ca, .45% P) or the basal with .05 or .10% P from monosodium phosphate (MSP), or .10% P from DFP with 60, 70, 75, 82, or 91% NAC soluble P. Each diet was fed to six pen replicates of eight chicks per pen for 14 d (58 to 402 g). Growth rate, feed/gain, and tibia breaking strength and ash concentration were improved (P < .001) by P supplementation, regardless of P source. Tibia strength and ash were regressed on P intake, and slope-ratios were calculated to assess the relative bioavailability of P in the DFP sources. The bioavailabilities of P in the 60, 70, 75, 82, and 91% NAC soluble DFP sources, relative to MSP (given a value of 100), were 81, 75, 84, 84, and 91%, respectively (linear, P < .08). In Exp. 2, 35 individually penned pigs were fed a corn-soybean meal basal diet (.95% lysine, .75% Ca, .33% P) or the basal with .15% P from MSP or from the five DFP sources. Each diet was fed to five pigs for 33 d (15.0 to 35.9 kg). Growth rate, feed/gain, and breaking strength of the metacarpals, metatarsals, and femurs were improved (P < .001) by MSP and DFP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883625 TI - The effect of dietary protein on performance and immune response in weanling pigs subjected to an inflammatory challenge. AB - A total of 96, 21-d-old, crossbred weanling pigs (average initial weight was 6.0 kg) were assigned to one of six treatments to investigate the effect of dietary protein on performance and immune function of Escherichia coli lipopolysaccharide (LPS)-challenged and unchallenged pigs. A control diet was formulated to contain 14.7 MJ of DE/kg, 14 g of CP/MJ of DE, and 7 g of lysine/100 g of CP. Diets low and high in protein were formulated by changing protein levels to 60 or 120% of the control diet. On d 7 and 21, pigs were challenged with either a LPS solution or a saline solution. Lymphocyte blastogenesis was measured 2 d after LPS challenges and antibody response to sheep red blood cells (SRBC) or ovalbumin was measured 3 d after the challenges. Gain and feed consumption were determined 3 d after each LPS injection and at weekly intervals for a total period of 5 wk. Injection of LPS decreased daily gain, feed intake, feed efficiency, and efficiency of protein utilization (P < .05). No interactive effects between LPS challenge and dietary protein were observed for pig performance (P > .10). Daily gain and feed efficiency were improved when protein level was increased from 60 to 100% of the control diet (P < .01). Efficiency of protein utilization for weight gain was lower when the 120% protein diet was fed (P < .01). Antibody response to SRBC or ovalbumin was not affected by treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883626 TI - Effects of diet acidity and protein level or source of calcium on the performance, gastrointestinal content measurements, bone measurements, and carcass composition of gilt and barrow weanling pigs. AB - A total of 228 crossbred weanling pigs (average age of 25 d and BW of 6.44 kg) were used in two trials to evaluate the responses to sex, diet acidity, protein level, and source of calcium on the performance, gastrointestinal digesta measurements, bone measurements, and carcass composition. Diet acidity was manipulated by varying the sources of supplemental phosphorus in the diets. Trial 1 (5 wk) was conducted as a 2 x 3 x 2 factorial to evaluate sex (gilts and barrows), diet acidity (pH 5.9 and .90% P, pH 6.1 and .63% P, and pH 6.9 and .63% P), and level of protein (16 and 22% CP). In Trial 2 (6 wk), diet acidity (pH 5.5, 5.9, and 6.8, all with .7% P) and Ca sources (CaCO3 and CaSO4) were used with gilts and barrows. The sex x diet acidity interactions were significant for ADG in both trials. Barrows seemed to respond to both the more acidic diets and the buffered phosphate diets even though the pH was less acidic than that of the unbuffered diets. Gilts responded only to the more acidic diets. In Trial 1, gilts ate more and grew faster (P < .05) than barrows, but no sex effects on performance were observed in Trial 2. Pigs fed 22% CP diets grew faster (P < .001) and more efficiently (P < .001) than did pigs fed 16% CP diets, but protein level x diet acidity and protein level x sex interactions were not significant. Stomach digesta DM, pH, and titration value were not consistently influenced by sex and diet acidity in Trials 1 and 2, by protein level in Trial 1, and by calcium source in Trial 2. Only the sex x diet acidity interaction for stomach DM tended to be significant in both trials; gilts fed the less acidic diets had the lowest DM, whereas barrows fed the more acidic diets had the lowest DM values. Although not significant in every case in both trials, bone (average of metacarpal and metatarsal) volume was lower and specific gravity and shear stress values were higher for gilts than for barrows. Pigs fed 16% CP diets had higher specific gravity (P < .05) and stress (P < .06) values than pigs fed 22% CP diets. A protein level x diet acidity interaction (P < .03) for stress suggested that pigs fed 22% CP diets were unaffected by diet acidity, whereas pigs fed 16% CP had the highest stress values when fed the more acidic diet and the lower P level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883627 TI - Bioavailability of zinc from inorganic and organic sources for pigs fed corn soybean meal diets. AB - Two experiments were conducted with pigs 1) to determine the effect of supplemental Zn on growth performance, bone Zn, and plasma Zn in pigs fed Zn unsupplemented, corn-soybean meal diets and 2) to assess bioavailability of Zn from inorganic and organic Zn sources. In both experiments, weanling pigs were fed a diet with no supplemental Zn for 5 wk to deplete their Zn stores. In Exp. 1, 192 pigs were fed a corn-soybean meal diet (growing diet, 32 mg/kg of Zn; finishing diet, 27 mg/kg of Zn) supplemented with feed-grade ZnSO4.H2O to provide 0, 5, 10, 20, 40, and 80 mg/kg of supplemental Zn. Supplemental Zn did not affect weight gain, feed intake, or gain/feed during either the growing or the finishing period (P > .05). However, bone and plasma Zn concentrations increased linearly (P < .01) in response to supplemental Zn at dietary Zn levels between 27 mg/kg (basal) and 47 mg/kg (breakpoint). In Exp. 2, three levels of supplemental Zn from ZnSO4.H2O (0, 7.5, and 15 mg/kg of supplemental Zn) were used to construct a standard curve (metacarpal, coccygeal vertebrae, and plasma Zn concentrations regressed on supplemental Zn intake; R2 = .93, .89, and .82, respectively). From the standard curve, the bone and plasma Zn concentrations obtained from pigs fed 15 mg/kg of supplemental Zn from ZnO and 7.5 mg/kg of supplemental Zn from Zn methionine (ZnMET) and Zn-lysine (ZnLYS) were used to calculate bioavailable Zn via multiple linear regression, slope-ratio analysis. The estimates of Zn bioavailability differed depending on which variable was used. Overall trends indicated the following rankings: ZnSO4.H2O > ZnMet > ZnO > ZnLys. PMID- 7883628 TI - Effect of spray-dried porcine plasma protein on feed intake, growth rate, and efficiency of gain in mice. AB - One hundred eight mice were weaned at 21 +/- 1 d and allotted to four dietary treatments: 1) control, 2) control + 4% spray-dried porcine plasma protein (SDPP), 3) control + 8% SDPP, and 4) control + 12% SDPP. Daily gain for males increased with increasing SDPP during wk 1 (P < .01), wk 2 (P < .01), and for the entire 3 wk (P < .01). Daily gain increased quadratically with increasing SDPP for females during wk 1 (P < .05). During the 3rd wk, ADG decreased for females with increasing SDPP (P < .05). Daily feed intake increased linearly (P < .01) with increasing SDPP in all periods. Gain-to-feed ratio (G/F) increased with increasing SDPP during wk 1 (P < .01) and for the first 2 wk (P < .05). During wk 3, G/F decreased with increasing SDPP level (P < .01). Gain-to-feed ratio of females responded quadratically to increasing SDPP during wk 1 (P < .05), whereas G/F of males increased linearly with increasing SDPP level. Gain-to-feed ratio for the entire trial was unaffected by treatment among females (P = .82) but increased linearly with increasing SDPP levels among males (P < .01). Liver weight increased quadratically with increasing SDPP levels for males (P < .05) and females (P < .05). Treatment effect on liver weight per kilogram BW.75 approached significance (P < .10) in females. Male liver weight/100 g BW and liver weight per kilogram BW.75 responded quadratically to increasing SDPP levels (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883629 TI - Effects of basic fibroblast growth factor and heparin on follicle-stimulating hormone-induced steroidogenesis by bovine granulosa cells. AB - The objectives of the present study were to determine the effect of and interaction between basic fibroblast growth factor (bFGF) and heparin, a major bFGF-binding protein, on bovine granulosa cell estradiol and progesterone production. Cells from small (1 to 5 mm) follicles were collected from cattle, cultured for 2 d in medium containing 10% fetal calf serum, and then treated for 1 d with bFGF and(or) heparin in serum-free medium. Treatment with .1 to 10 micrograms/mL of heparin for 1 d had no effect (P > .05), whereas 100 micrograms/mL of heparin inhibited (P < .05) FSH-induced estradiol production by bovine granulosa cells. Treatment with .1 to 1.0 ng/mL of bFGF for 1 d, supplied with human serum albumin as a carrier protein, inhibited (P < .05) FSH-induced estradiol production by bovine granulosa cells, with the greatest inhibition detected at 1.0 ng/mL; coculture with 10 micrograms/mL of heparin did not influence these effects. In comparison, .1 ng/mL of bFGF supplied carrier-free had no effect (P > .05) on FSH-induced estradiol production, whereas 1.0 to 100 ng/mL of carrier-free bFGF inhibited (P < .05) FSH-induced estradiol production, with the greatest inhibition detected at 100 ng/mL. The presence of heparin (10 micrograms/mL) had variable effects on granulosa cell estradiol and progesterone production inhibited by carrier-free bFGF. These results indicate that bFGF may play a significant role in FSH-modulated granulosa cell steroidogenesis during follicular development in cattle. PMID- 7883630 TI - Body energy reserves influence the onset of luteal activity after early weaning of beef cows. AB - The influence of body energy reserves on the onset of luteal activity and concentrations of LH and IGF-I in serum was evaluated in postpartum anestrous beef cows after early weaning. Multiparous Hereford and Hereford x Angus cows (n = 24) were fed during gestation to establish body condition scores between 3 and 6 (BCS, 1 = emaciated; 9 = obese) at parturition. Concentrations of progesterone in plasma were determined weekly for 5 wk postpartum (PP). Anovulatory cows and their calves (n = 19) were confined in stalls on d 40 +/- 3 PP. Jugular cannulas were inserted on d 44 +/- 3 PP, and calves were weaned (d 0) the following day. Blood samples were collected from all cows for 4 h (every 10 min) before weaning and on d 1, 2, 4, 6, 8, and 10 after weaning and LH was quantified. Progesterone was quantified in daily blood samples until d 10, and in samples taken twice weekly until d 46. Within 25 d after weaning, 100% of the cows with BCS < or = 5 at weaning (n = 7) had initiated luteal activity, whereas only 43% (P < .01) of the cows with BCS < 5 (n = 12) had luteal activity. Mean serum IGF-I concentrations were correlated with BCS (r = .50; P < .05). Frequency of LH pulses was influenced (P < .01) by body condition at weaning but was not influenced by day after weaning. The number of LH pulses at weaning, serum IGF-I, and the interval to the onset of ovarian activity after early weaning of anestrous beef cows were influenced by BCS. PMID- 7883632 TI - Luteolytic effect of prostaglandin F2 alpha and two metabolites in ewes. AB - Twenty-three ewes were used in an experiment to determine the point in metabolism at which prostaglandin (PG) F2 alpha loses its luteolytic activity. Ewes exhibited at least one normal estrous cycle (15 to 19 d) and then were randomly assigned to one of four treatment groups: 1) control, 2) PGF2 alpha, 3) 15-keto PGF2 alpha, or 4) 13,14-dihydro-15-keto-PGF2 alpha (PGFM). Each ewe received an i.m. injection of the designated treatment (5 mg in 1 mL of sterile saline) during the midluteal phase of the estrous cycle (d 8, 9, 10, or 11 after estrus). An identical second injection was given to each ewe 3 h after the first injection. Beginning at 9 h after injection, concentrations of progesterone were lower (P < .01) in the PGF2 alpha-treated ewes than in ewes in the other three groups. These differences were maintained throughout the duration of the 48-h sampling period in five of the six ewes that received PGF2 alpha. None of the ewes in the other three treatment groups exhibited any change in concentrations of progesterone. Ewes were classified as completing luteolysis if concentrations of progesterone decreased to less than 1 ng/mL within 48 h after the first injection. Five of the six ewes receiving PGF2 alpha completed luteolysis (P < .05), whereas none of the ewes in the other three groups completed luteolysis. The interestrous interval was reduced by approximately 5 d in the PGF2 alpha treated group compared with the other three treatment groups (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883631 TI - Long-term effects of human growth hormone-releasing hormone and photoperiod on hormone release and puberty in dairy heifers. AB - Forty-eight Holstein dairy heifers (98.9 kg BW; 3 mo old) were subjected for 246 d to twice-daily s.c. injections of saline (CTL) or human growth hormone releasing hormone (GRH; 5 micrograms/kg BW) and to photoperiods of 8 h of light (L): 16 h of dark (D) or 16L:8D according to a 2 x 2 factorial arrangement of treatments. Jugular blood samples were collected from 16 heifers at 3, 4, 8, and 11 mo of age to monitor prolactin, growth hormone, and estradiol-17 beta. Plasma progesterone concentrations were monitored weekly in all heifers as an index of puberty (> 1 ng/mL). Growth hormone release was induced by GRH (P < .001) throughout the trial; area under the GH curve (AUC) averaged 1,582 vs 3,643 ng.min-1.mL-1 in CTL vs GRH heifers. However, GRH-induced GH response was less (P < .05) after the second daily injection. There was also an interaction (P = .08) between GRH, photoperiod, and days of treatment on GRH-induced GH response; AUC was greater in GRH-16L:8D than in GRH-8L:16D heifers at 3 mo but less at 8 mo of age. The PRL concentrations were similar for both photoperiods at 3 mo (36.4 vs 41.7 ng/mL) and 8 mo (16.2 vs 12.8 ng/mL) of age but were greater in 16L:8D vs 8L:16D heifers at 4 mo (18.4 vs 39.3 ng/mL) and 11 mo (26.3 vs 44.1 ng/mL) of age (photoperiod x day interaction, P < .001). Photoperiod of 16L:8D vs 8L:16D reduced (P < .01) weight at puberty in CTL heifers (251 vs 303 kg BW) and to a lesser extent in GRH-treated heifers (271 vs 284 kg BW; GRH x photoperiod interaction, P = .10). In conclusion, GH response is maintained throughout 8 mo of GRH treatment, and a 16L:8D photoperiod will reduce age and weight at puberty in heifers. Furthermore, refractoriness to photoperiod-induced PRL changes was detected. PMID- 7883633 TI - Effect of dietary copper, iron, and molybdenum on growth and copper status of beef cows and calves. AB - A study was conducted to determine the effects of copper (Cu) depletion by feeding diets high in either iron (Fe) or molybdenum (Mo) on performance and Cu status of beef cows and calves. Thirty-eight 2-yr-old beef heifers, entering the last one-third of gestation, were randomly assigned by expected calving date to one of four diets: 1) control (CON; corn silage-soybean meal-based diet, 4 mg of Cu/kg), 2) control + 600 mg of Fe (as FeCO3)/kg, 3) control + 5 mg of Mo (as Na2MoO4)/kg, and 4) control + 10 mg of Cu (as CuSO4)/kg. From d 28 until after the end of the calving season (d 125), heifers receiving supplemental Cu had higher (P < .05) plasma Cu levels and ceruloplasmin activities than heifers fed the other diets. By d 224, plasma Cu concentrations of heifers fed the CON and Fe diets had increased to levels similar to those observed in the Cu-supplemented heifers, whereas the Mo heifers exhibited the lowest (P < .05) plasma Cu of the four treatments from d 168 through the remainder of the 280-d trial. Plasma Cu concentrations and ceruloplasmin activities were greater (P < .05) in Cu supplemented than in non-Cu-supplemented calves (diets 1, 2, and 3) from d 168 onward, and the Fe- and Mo-supplemented calves did not differ in either measurement at any time during the trial. Rate of gain did not differ among calves fed the CON, Fe- or Cu-supplemented diets, whereas the Mo-supplemented calves gained at a much slower (P < .05) rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883634 TI - Bioavailability of feed-grade copper sources (oxide, sulfate, or lysine) in growing cattle. AB - Plasma Cu concentrations and ceruloplasmin (a Cu metalloenzyme) activity were used to assess relative Cu bioavailability from different Cu sources for growing cattle. In Exp. 1, 18 calves (average BW 207 +/- 7.7 kg) that had been fed Cu deficient diets since birth were randomly assigned to treatment. Treatments consisted of control (n = 3) or 30 mg/d of supplemental Cu (n = 5/treatment) from Cu oxide (CuO), Cu sulfate (CuSO4), or Cu lysine. Blood samples were obtained for plasma Cu and ceruloplasmin activity on d 0, 7, 14, and 21. Plasma Cu and ceruloplasmin activity were greater (P < .05) on d 7, 14, and 21 for calves supplemented with CuSO4 than for controls. Copper status of calves fed Cu lysine did not differ from that of calves fed CuSO4. Compared with d-0 values, plasma Cu concentrations by d 21 had increased by 95 and 98% in calves supplemented with CuSO4 and Cu lysine, respectively. Copper oxide supplementation did not increase Cu status above that observed in control calves. In Exp. 2, 36 calves (average BW 211 +/- 4.4 kg) were used to compare the relative bioavailability of Cu from CuO and CuSO4 when supplemented to corn silage-based diets high in the Cu antagonists iron (Fe) or molybdenum (Mo). Treatments consisted of no supplemental Cu or 8 mg of supplemental Cu/kg diet from either CuSO4 or CuO. Within each Cu treatment, diets were supplemented with 600 mg of Fe or 5 mg of Mo/kg diet. In calves fed 5 mg of Mo/kg, plasma Cu was lower (P < .05) in those fed no supplemental Cu or CuO compared with calves fed CuSO4 by d 91 and at subsequent sampling dates throughout the 154-d study. Plasma ceruloplasmin activity was decreased (P < .01) by Mo and was increased (P < .05) by CuSO4 compared with CuO. Based on plasma Cu and ceruloplasmin activity, CuSO4 and Cu lysine were similar in bioavailability, but CuO was essentially unavailable. PMID- 7883635 TI - Effect of dietary canola on fatty acid composition of bovine adipose tissue, muscle, kidney, and liver. AB - The purpose of this study was to determine effects of feeding canola and soybean products as protein supplements on fatty acid composition of adipose tissue and muscle of slaughter bulls and steers and on fatty acid composition of kidney and liver total lipids of bulls. Products included canola meal (CM), extruded canola (EC, full-fat), ground canola (GC, full-fat), soybean meal (SBM), and extruded soybeans (ES, full-fat). Tissues were obtained at slaughter from 75 crossbred beef bulls and 50 crossbred beef steers fed corn silage (17.2 to 29.7% of DM), ground corn (56.5 to 75.0% of DM), and protein supplements (6.8 to 21.6% of DM). The DMI was not influenced by dietary fat in either trial. Gain: feed was greater (P < .05) for bulls fed CM than for bulls fed ES, EC, or GC. Carcasses were not influenced appreciably by dietary fat. Adipose tissue of EC-fed cattle had the lowest percentage of 16:0 (P < .05, vs SBM, CM, and GC), whereas both EC- and GC fed cattle had the highest 18:0 (P < .05). In muscle (pectoral), EC-fed bulls had a higher percentage of 18:1 than SBM-fed bulls (P < .05), and EC-fed steers had the lowest 16:0 and 16:1 and highest 18:0, 18:3, and 20:1 (P < .05). Kidney total lipids of EC- and GC-fed bulls had the lowest percentage of 16:0 and highest 18:1 and 18:3 (P < .05); bulls fed ES had the highest percentage of 18:2. Liver-lipid 16:0 was highest in ES-fed bulls and lowest in EC-fed bulls, which also had the highest 18:0 (P < .05). Bulls fed EC and GC had the highest 18:3 and 20:5 (P < .05). In conclusion, dietary full-fat canola and in some cases full-fat soybeans altered the fatty acid composition of lipids of adipose tissue, muscle, kidney, and liver of beef cattle. PMID- 7883636 TI - Breed differences and genetic parameters for body composition traits in beef cattle. AB - The recent scientific literature was reviewed to summarize breed differences and genetic parameters for carcass traits in beef cattle. Heritability estimates were generally moderate to large, suggesting good potential for accurate genetic selection for a given individual carcass characteristic. However, effectiveness of multiple-trait selection for some trait combinations could be slowed by genetic antagonisms between traits, suggesting the use of terminal breeding systems with complementary sire and dam genetic types. Individual and maternal heterosis estimates from age-constant analyses were numerically positive for most carcass traits, although estimates from weight-constant analyses were generally nonsignificant. Potential contributions to improved carcass composition from crossbreeding would primarily result from genetic complementarity rather than heterosis. Considerable variation exists between breeds for body composition, and breed rankings vary across different traits. Studies have consistently indicated reduced meat tenderness for Bos indicus compared with Bos taurus breeds. Some differences in breed rankings for marbling vs tenderness were noted. If the U.S. beef industry shifts toward a more value-based marketing system, some genetic concerns will include 1) an apparent antagonistic relationship between marbling and cutability across breeds and within some breeds, 2) inconsistency of beef tenderness, particularly in Bos indicus cattle, 3) the effect of increased leanness on female reproductive performance, and 4) the extent to which terminal breeding systems can be used. PMID- 7883637 TI - Implications of genetic changes in body composition on beef production systems. AB - Changing the body composition of beef has implications for the entire beef production system. The dynamic nature of an animal's body composition and the production system itself make predictions of the implications of genetic change in body composition difficult. The cow-calf, stocker, and feeder segments of the production system will be affected differently. Leaner cattle tend to be slaughtered at heavier weights. Heavier weights effectively reduce composition differences of slaughter beef to less than the genetic differences. The effects of four pricing scenarios on slaughter weight and composition were evaluated for two leaner genotypes, one with no change in marbling and one with reduced marbling. A genetic difference of 1.0 yield grade at the same carcass weight resulted in slaughter beef that differed by .4 to 1.0 yield grade because of increased slaughter weights. Separate analyses suggested the stocker segment of beef production will be least affected by changes in body composition. Genotypes that are best fitted to slaughter requirements will have the most flexibility in types of stocker systems that can be used. The cow-calf segment of beef production has several options to adapt to leaner cattle. Management to reduce nutritional stress on leaner cows may be required by some producers. Increased selection for reproductive traits in cow genotypes may be needed. An alternative to selection for reproduction is terminal crossing to partially disassociate the slaughter animals' genotype from the cow's genotype. PMID- 7883638 TI - Rapid communication: dinucleotide repeat polymorphism of rainbow trout, FGT2. PMID- 7883639 TI - Rapid communication: dinucleotide repeat polymorphism of rainbow trout, FGT3(1). PMID- 7883640 TI - Rapid communication: dinucleotide repeat polymorphism of rainbow trout, FGT4(1). PMID- 7883641 TI - Rapid communication: dinucleotide repeat polymorphism of rainbow trout, FGT5(1). PMID- 7883642 TI - Intestinal carriage of campylobacters, salmonellas, yersinias and listerias in pigeons in the city of Barcelona. AB - The faecal bacterial flora of pigeons, which may be the source of infectious diseases in man, was studied in the city of Barcelona. Four hundred cloacal specimens were examined for Campylobacter jejuni, Camp. coli, Salmonella spp., Yersinia spp. and Listeria spp., over a 12 month period. Campylobacter jejuni was the most frequently isolated micro-organism, found in 105 pigeons (26.2%), with a greater incidence in the districts of the city with a high density of pigeons and without seasonal variation. Salmonella spp. were isolated from six specimens (1.5%) and Yersinia intermedia was isolated from only one pigeon. PMID- 7883643 TI - The effect of sewage sludge treatment processes on oocysts of Cryptosporidium parvum. AB - The effect of common sewage sludge treatment processes on oocysts of the coccidian protozoan Cryptosporidium was evaluated in laboratory simulations. The ability of primary sewage sedimentation to remove Cryptosporidium oocysts was found to be poor. Thermophilic (55 degrees C) aerobic digestion and sludge pasteurization at the same temperature were found to be effective treatments to inactivate Cryptosporidium oocysts. Approximately 10% of the oocyst population were found to be viable after 18 d exposure to mesophilic (35 degrees C) anaerobically digesting sludge. The viability of Cryptosporidium oocysts decreased within the range 20-40% in sludge-treated soil mesocosms over 30 d. The survival results obtained, however, indicated that oocysts would survive well beyond this period. PMID- 7883644 TI - The antimicrobial activity of hexapeptides derived from synthetic combinatorial libraries. AB - A series of peptides identified through the use of synthetic hexapeptide combinatorial libraries (represented by the formula Ac-RRWWCO-NH2) were examined for their antimicrobial activity against five different micro-organisms. Their toxicity was also evaluated in an in vitro haemolytic assay. The peptides showed activity against the five micro-organisms, although higher activities were found against Gram-positive bacteria. Both growth inhibition and cell viability assays were carried out to demonstrate the bactericidal activities of these peptides against two of the micro-organisms tested. The dimeric cystine forms of these peptides were shown to have biological activities identical to the monomeric forms. PMID- 7883645 TI - A novel approach to mode of action of cationic biocides: morphological effect on antibacterial activity. AB - A new concept for the mode of action of cationic biocides is proposed in which the antibacterial activity of cationic disinfectants is ascribed essentially to molecular organizations of cations within aggregates, i.e. the activity is determined by the size of aggregates and number of active molecules comprising the aggregate. On the basis of the new concept, the morphological effect of disinfectants in aqueous solution on the antibacterial activity is discussed for low molecular weight phosphonium salts with single and double long alkyl chains (carbon number 14). The proposed new concept can be applied to all phenomena reported previously in antibacterial activity of cationic biocides and this concept is very important from the viewpoint of molecular design of more active cationic biocides. PMID- 7883646 TI - Non-culturable Legionella pneumophila associated with Acanthamoeba castellanii: detection of the bacterium using DNA amplification and hybridization. AB - The intracellular localization of Legionella pneumophila serogroup 1 within Acanthamoeba castellanii rendered the bacteria non-culturable on supplemented BCYE agar. DNA amplification, using two 19-mer primers, and hybridization using a 25-mer oligonucleotide probe, permitted detection of Leg. pneumophila in approximately 81% (29/36) of samples where the bacteria could not be detected using culture. A combination of co-cultivation of samples with Leg. pneumophila naive A. polyphaga or Hartmannella vermiformis, incubation in a defined liquid medium or use of catalase indicated that approximately 31% (9/29) of the samples contained Leg. pneumophila which were viable although not culturable. PMID- 7883647 TI - Comparative study of the growth of Listeria monocytogenes in defined media and demonstration of growth in continuous culture. AB - A basic requirement for physiological studies with Listeria monocytogenes is a chemically defined medium that supports growth of the bacterium in batch and continuous culture. A number of such media have been devised but comparative studies of their efficiency are few and none has been used in continuous culture. Six of the media were compared for their ability to sustain sequential growth of L. monocytogenes in static and aerated batch culture with glucose as sole carbon source. The most suitable, judged on the basis of ease of preparation, growth rate and yield, was that of Trivett and Meyer (1971). This medium was shown to support growth of L. monocytogenes NCTC 7973 in continuous culture in a chemostat. A lytic phenomenon, noted with the same strain under anaerobic conditions and in batch culture in the chemostat, is discussed. PMID- 7883648 TI - A numerical taxonomic study of fluorescent Pseudomonas strains isolated from natural mineral waters. AB - Forty-six strains of fluorescent pseudomonads, isolated from natural mineral waters, together with 12 strains from clinical material and 44 reference strains, were phenotypically classified by 281 characteristics. The data were processed by the Dice similarity coefficient and unweighted pair group algorithm with arithmetic averages. Eight clusters were defined at the 62% similarity level. Clusters I, II and IV were further divided into nine subclusters. Virtually all the mineral water strains fall into three groups: Ib (eight strains), IIa (14 strains) and V (16 strains). Subclusters Ib and IIa included natural mineral water strains only. Cluster V contained 13 mineral water strains and three culture collection strains of Pseudomonas fluorescens biovar III. DNA/DNA hybridization studies are needed to define the taxonomic status of these three groups within the genus Pseudomonas. PMID- 7883649 TI - The effect of hydroxycinnamic acids and potassium sorbate on the growth of 11 strains of spoilage yeasts. AB - Hydroxycinnamic acids and their derivatives occur widely in plants, fruits and wine. The effect of the common hydroxycinnamic acids (caffeic, coumaric and ferulic acids), at concentrations of 100 and 500 mg l-1, on growth of 11 strains of spoilage yeasts was measured spectrophotometrically and compared with that of potassium sorbate. Ferulic acid was the most generally inhibitory hydroxycinnamic acid. At 500 mg l-1 it appreciably inhibited Pichia anomala, Debaryomyces hansenii and Saccharomyces cerevisiae and prevented detectable growth of one strain each of P. anomala and D. hansenii. Caffeic acid was the least inhibitory compound and coumaric acid had an intermediate effect. The more resistant strains of yeast were P. membranaefaciens, Saccharomycodes ludwigii and Zygosaccharomyces bailii. Sensitivity to hydroxycinnamic acid was, in general, associated with sensitivity to potassium sorbate; at a given concentration potassium sorbate was more inhibitory than were any of the hydroxycinnamic acids. PMID- 7883650 TI - Chelation of copper reduces inhibition by oxidized lipoproteins of endothelium dependent relaxation in porcine coronary arteries. AB - We examined the effect of dialyzing oxidized low-density lipoprotein (oLDL) against Krebs-Ringer solution, in the absence (yielding d-oLDL) or presence (yielding EDTA-oLDL) of ethylenediamine tetraacetic acid (EDTA), to investigate the mechanism that underlies the inhibition of endothelium-dependent relaxation (EDR) by o-LDL. Oxidation of LDL by exposure to Cu2+ resulted in the formation of a thiobarbituric acid-reacting substance (TBARS) and lipid hydroperoxide (LPO). At a concentration of 5 mg/dl, d-oLDL markedly attenuated EDR in the porcine coronary artery. Analysis of d-oLDL by gel filtration revealed that TBARS was ditributed in both the lipoprotein and the aqueous phases, whereas LPO was present only in the lipoprotein particles. Lysophosphatidylcholine (LPC), which has been suggested to be responsible for the impairment of EDR by oLDL, was present not only in the lipoprotein but also in the aqueous phase. However, EDR inhibitory activity was observed only in the oLDL particles, not in the aqueous phase. Almost all Cu2+ associated with the oLDL particles was removed by dialysis of oLDL against Krebs-Ringer solution containing EDTA. EDTA-oLDL or native LDL, at concentrations as high as 75 mg/dl, exerted only a moderate inhibitory action on EDR, Both TBARS and LPO in EDTA-oLDL were distributed only in the lipoprotein particles, not in the aqueous phase. These results demonstrate that the impairment of EDR by oLDL is related both to LPO and to transition metal ions such as Cu2+ associated with the lipoprotein particles, not to the amount of the TBARS or negative charge, and that factors other than LPC may affect EDR. PMID- 7883651 TI - Determinants of collateral development in a canine model with repeated coronary occlusion. AB - It is now accepted that repetitive 2-min coronary occlusion can develop collateral vessels to the area perfused by the occluded coronary artery. However, which factors influence collateral development has yet to be fully elucidated. The goal of the present study was to identify the determinants of the rate of coronary collateral development in dogs undergoing repeated coronary occlusion. The study was conducted in 19 conscious dogs instrumented for measurements of a subendocardial segment length in the area perfused by the left circumflex coronary artery (LCCA), LCCA flow, and left ventricular pressure. An externally inflatable pneumatic occluder was placed around the LCCA. After the recovery from surgery, 2-min LCCA occlusions were conducted eight times daily. Following 141 +/ 61 (SD) LCCA occlusions (20 +/- 7 days), an LCCA occlusion produced no reduction in segment shortening and negligible reactive hyperemia. The total number of LCCA occlusions needed for adequate collateral development (the rate of collateralization) correlated well with the severity of myocardial ischemia during the first occlusion, which was determined mainly by the extent of postsurgical initial collateral circulation. On the other hand, the response to the ischemic stimulus in the later stage of collateral development was independent of the extent of development of the initial postsurgical collaterals. It is concluded that the overall rate of collateral development is slower in dogs with initially poorer collaterals; however, the response of each dog to the ischemic stimulus in the later stage of collateral development was similar among dogs regardless of the extent of the initial collaterals. PMID- 7883652 TI - Rate-dependent prolongation of action potential duration in single ventricular myocytes obtained from hearts of rats with streptozotocin-induced chronic diabetes sustained for 30-32 weeks. AB - We examined the characteristics of the action potentials of single ventricular myocytes obtained from the hearts of rats with chronically-induced diabetes. Male Wistar rats were made diabetic by injecting streptozotocin (65 mg/kg) and 30-32 weeks later the hearts were excised and used for an electrophysiological study. Action potentials were recorded from isolated right ventricular myocytes by an electrode fabricated for patch clamp in the whole-cell recording configuration. The action potential durations (APDs) of steady state chronic diabetic rat myocytes were longer than those of age-matched normal rat myocytes at all levels of repolarization (APD25, APD50, APD75, and APD90). As the stimulation frequency was increased (0.2-2 Hz), the APDs were lengthened in both diabetic and normal rats, and the difference of APDs between the groups was greater when the stimulation frequency was higher. When we examined alterations of APDs under conditions of train stimulation (2Hz, 20 stimuli), (1) the APDs in both groups were prolonged, and (2) the degree of prolongation of APD was significantly greater and the rate of APD prolongation was significantly faster in myocytes from the diabetic rats. The prolongation of APD in these heart cells is probably secondary to alteration of the transient outward current Ito, and sheds light on repolarization abnormality in cases of diabetic cardiomyopathy. PMID- 7883654 TI - Usefulness of transesophageal echocardiography for guiding pulmonary artery catheter placement in the operating room. AB - The usefulness of transesophageal echocardiography (TEE) for guiding the placement of a pulmonary artery (PA) catheter was evaluated in 31 patients (TEE group); 31 patients who were treated before TEE guidance was used (control group). In the control group, use of the PA catheter was abandoned in two patients; because of an unstable condition and marked arrhythmias, respectively. The key findings for TEE guidance were: (1) pulsatile to-and-fro movement of the balloon, i.e., "shuttle movement" and (2) loss of shuttle movement at wedging of the balloon, i.e., "anchoring sign." When the PA catheter did not enter the right vertricle (RV), the balloon was found to be in the inferior vena cava or the right atrium (RA) without shuttle movement. Coiling of the catheter was suggested in the latter situation. Coiling also occurred in the RV, often associated with frequent arrhythmias. These findings indicate that the catheter should be withdrawn once. TEE allowed for readjustment of the catheter tip position by enabling the balloon to be wedged twice. An excessively deep placement of the catheter tip was seen in 5 of the controls, but in none of the TEE group. Biplane TEE was found to be advantageous for guiding PA catheter placement and for visualizing the RV inflow and outflow tract in a single view, with the shuttle movement of the balloon in its long axis. TEE acts as an "eye" in the operating room, as does fluoroscopy, enabling smooth placement of the PA catheter. PMID- 7883653 TI - Asynchronous volume changes of the two ventricles after Fontan operation in patients with a biventricular heart. AB - Coordinated contraction of the ventricle is an important determinant of pump function, which seems to be particularly important in Fontan circulation with one pumping ventricle. We analyzed the synchronism of contraction of the two ventricles in 11 patients with a biventricular heart who had undergone Fontan operation. Curves representing ventricular volume changes in a cardiac cycle measured on angiograms were smoothed and divided into 20 segments. We calculated the number of segments of the same directional volume changes (synchronous changes) between the two ventricles (synchronous ratio). We also calculated the total volume of the two ventricles (the two as one whole ventricle) by adding their volumes in each segment and calculated the ratio (stroke volume ratio) of the aortic stroke volume from the whole ventricle to the sum of stroke volumes of the morphological right and left ventricles. If the two ventricles ejected the blood in a completely synchronous manner, these ratios should be 1.0. In seven patients with synchronous ratios of 0.75 or greater and a stroke volume ratio of greater than 0.95, the cardiac index was 3.2 +/- 0.3 l/min/m2, the maximum total volume (corresponding to end-diastolic volume) was 106 +/- 45% normal, and the ejection fraction was 0.44 +/- 0.10. In four patients with ratios of less than 0.70 and 0.95, respectively, the parameters were 2.4 +/- 0.5 (P < 0.05), 193 +/- 92%, and 0.33 +/- 0.08, respectively. The synchronous ratio was inversely correlated with cardiac output. In conclusion, synchronism of the cardiac cycle of the two ventricles affects Fontan circulation in patients with a biventricular heart. PMID- 7883655 TI - Echocardiographic evaluation of hearts with twisted atrioventricular connections (criss-cross heart). AB - An echocardiographic study was performed on seven patients with twisted atrioventricular connections (criss-cross heart) relative to the usual atrial arrangement. The atrioventricular connections were concordant in five patients and discordant in two. The ventriculoarterial junction was either double-outlet right ventricle (n = 6) or discordant connections (n = 1). Associated cardiac defects were ventricular septal defect (n = 7), pulmonary stenosis (n = 5), straddling tricuspid valve (n = 2), and straddling mitral valve (n = 1). Malalignment between the atrial and ventricular septum was the most important feature of this disease and resulted in altered spatial orientation of the trabecular ventricular septum, and recesses in the ventricles and the right atrium. When assessed by echocardiography, these anatomical features were not invariably recognized in every case, but they were dependent upon the type of atrioventricular connections and the presence of straddling of the atrioventricular valves. Left ventricular recess was the most consistent feature and was present in every patient, regardless of the atrioventricular connections. Right atrial recess was found in four of five patients with concordant atrioventricular connections but was not present in patients with discordant atrioventricular connections. Right ventricular recess was recognized as such in a single patient with concordant atrioventricular connection and straddling mitral valve. The trabecular septum was oriented in a horizontal plane in hearts with concordant atrioventricular connections and without atrioventricular valve straddling. The trabecular septum was oriented semivertically in all other hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883656 TI - Mycobacterium tuberculosis--from the gene to the diagnosis. PMID- 7883657 TI - Anti leishmanial therapy--the changing scene. PMID- 7883658 TI - Diagnosis of tuberculous meningitis by enzyme-linked immuno-sorbent assay (ELISA), using an affinity chromatography purified mycobacterial antigen. AB - Using an immunoabsorbent affinity chromatography, a mycobacterial antigen was isolated from culture filtrate of H37Ra Mycobacterium tuberculosis (MTB). The immunoabsorbents were prepared by coupling cynogen bromide-activated Sepharose-4B with human IgG antibody to MTB. Cerebrospinal fluids (CSF) from 10 culture positive, 30 culture negative patients with tuberculous meningitis (TBM) were assayed, for IgG antibody to this mycobacterial antigen by ELISA. CSFs from 50 patients with non-tuberculous neurological diseases were selected as control group. At a selected 'cut off' titre of 1:80, 21 out of 30 CSFs from culture negative patients gave positive results. No false negative result was observed in CSF from 10 culture positive patients with TBM. No false positive results were recorded in CSFs of 50 patients with non-tuberculous neurological diseases. Technical aspects involved in the isolation of this myobacterial antigen and its potential applications in the laboratory diagnosis of TBM have been emphasised in this study. PMID- 7883659 TI - Treatment of visceral Leishmaniasis unresponsive to pentamidine with amphotericin B. AB - Twenty five cases of visceral leishmaniasis unresponsive to Pentamidine were treated with Amphotericin B in the dose schedule of 0.75 mg per kg body weight I.V. on alternate days for total 15 infusions. Full cure was achieved in all twenty five (hundred per cent) cases, no significant toxicity was observed during as well as after treatment and none of the patients relapsed during twelve months follow-up. PMID- 7883660 TI - Experience with amphotericin B in sodium stibogluconate--unresponsive cases of visceral Leishmaniasis in north Bihar. AB - One hundred cases of Indian Kala-azar unresponsive to sodium stibogluconate (SSG) were treated with amphotericin B. The drug was given in the dose schedule of 0.75 mg/kg body weight on alternate days intravenously dissolved in 5 percent dextrose solution. After 15 infusions given over a period of 30 days, all cases became clinically and parasitologically cured. Mild adverse reactions were noted during therapy. No relapse was observed at follow up after 12 months. PMID- 7883661 TI - Osteomalacia--fifty five patients seen in a teaching institution over a 4 year period. AB - A retrospective analysis of 55 cases of osteomalacia shows that poor calcium intake and poor sunlight exposure are the most common causes for osteomalacia. However, in patients with normal nutritional history, other disorders such as renal tubular acidosis and tumour induced osteomalacia should be looked for. A careful drug history, particularly anticonvulsant use is essential. In 4 patients there was an association between anti-tuberculous drug use and osteomalacia. Further prospective studies are needed to determine the relationship between Rifamicin use and osteomalacia. PMID- 7883662 TI - A modified curriculum for clinical pharmacology during undergraduate training in India. AB - The present curriculum for clinical pharmacology during undergraduate medical training appears very inadequate as evidenced from the analysis of a questionnaire sent to all medical schools in the country. Recognising the need for the subject to be taught in a meaningful way and keeping in view the suggestions made through the questionnaire, a modified curriculum and evaluation of the course that spans through the clinical years of training is presented. PMID- 7883663 TI - Recovery positive exercise stress test: an indication for coronary artery disease. AB - The significance of ST depression occurring during exercise treadmill stress test has been well established. However, at times there may be no ST segment changes during exercise with changes occurring during the recovery phase. Out of the 1234 patients who underwent exercise stress test, 17 patients had ST segment changes confined to recovery phase. Coronary angiography performed in these 17 patients showed 11 patients had significant coronary artery disease (CAD), with nine patients having triple vessel disease and 2 having double vessel disease. Analysis showed there was no significant difference in the two groups of CAD and no CAD with respect to sex ratio, mean duration of exercise, maximal heart rate and double product achieved. CONCLUSION: Although, patients with recovery positive stress test may have normal coronary angiography, a large number of patients (64.7%) in our study had significant CAD. Hence, such patients should be subjected to another noninvasive test such as thallium perfusion scan or coronary angiography. PMID- 7883664 TI - Evaluation of apolipoproteins A1 and B in survivors of myocardial infarction. AB - Lipid profile of sixty survivors of myocardial infarction was studied and these results were compared with hundred age and sex matched controls. Seventy one percent had normal cholesterol (Ch). However, 80% of them had elevated serum Triglyceride (Tg) values. A decreased apolipoprotein A1 (apo A1) with an increased apolipoprotein B (apo B) values were observed in these patients. Ratio of apo A1 to apo B remained significantly low in survivors of myocardial infarction. It was seen that more abnormalities in patients were observed in apolipoprotein concentrations rather than lipoprotein or lipid concentration. PMID- 7883665 TI - Computer--aided drug interaction retrieval programme. AB - A drug interaction database has been created to include information on drug interactions based both on the generic and trade names of drugs. The database has approximately one thousand records that provide the information on drug-drug, food, smoke, alcohol interactions and a message to briefly describe the particulars of drug interactions. The computer programme was designed using Dbase III plus commands, to readily identify potentially significant interactions in a prescription. The computer outputs may be used to alert the physicians in time to take precautions and hence to reduce the incidences of adverse effects associated with drug interactions. This would result in reduction in hospital stay as well as reducing costs of medical care. This is urgently needed in public as well as private hospitals. PMID- 7883666 TI - Prolactin and cortisol levels in seizure disorders. AB - Levels of prolactin (PRL) and cortisol were estimated to find out the acute effects of generalised tonic clonic seizures (GTCS), partial seizures and pseudoseizures in 60, 18 and 9 patients respectively. Prolactin levels were estimated at 20, 60 and 120 minutes whereas, cortisol was estimated at 20, 60, and 120 minutes postictally. Cortisol and PRL estimation was also done in 10 healthy controls and 11 patients of epilepsy during interictal phase. Serum PRL levels were elevated (> 25 ng/ml) in 68.33% of GTCS and 11.11% of partial seizure cases. The peak levels were achieved in first 30 minutes after the seizures with a gradual return to base line during subsequent one hour. None of the patients with pseudoseizure showed any rise in serum PRL levels. The interictal PRL levels were normal in all the epileptics. Plasma cortisol levels were elevated during 60 to 120 minute postictal period in 45% of GTCS, 55.55% of partial seizures and 66.66% of pseudoseizure patients. Cortisol appears to be non-selectively triggered by all stressful events but postictal PRL estimation can help in differentiating pseudoseizures from GTCS. While an elevated PRL indicates the occurrence of grandmal seizure, a normal postictal PRL level does not always exclude epileptic seizure, specially a partial seizure. PMID- 7883667 TI - Serum pepsinogen levels in patients with gastro-duodenal lesions. AB - Serum pepsinogen (SP) levels were studied in 100 patients with gastroduodenal lesions, and 100 healthy volunteers. SP levels were significantly elevated in patients with duodenal ulcer (DU) and duodenitis compared to the controls. SP values above 150 ug Tyr/ml/24 hr were highly suggestive of duodenal ulcer disease. Age and sex of patients and controls did not influence SP levels. The mean values of SP in North India were found to be lower in both normal and DU subjects compared to the west. PMID- 7883669 TI - Hypozincemia in diabetes mellitus. AB - The present study was conducted on 20 age and sex matched healthy controls and 30 patients of diabetes mellitus. Serum zinc levels in diabetics were found to be significantly (p < 0.001) reduced as compared to healthy controls. There was no significant sex difference (P > 0.05) in serum zinc levels amongst diabetic patients and healthy controls. Hypozincema in diabetes mellitus may be due to altered zinc metabolism and oral zinc may have a role in therapy. PMID- 7883668 TI - Helicobacter pylori in dental plaque of children and their family members. AB - A prospective study was undertaken to determine the presence of Helicobacter pylori in the dental plaque of children and their family members. 22 children (age range: 2-12 years; males: 16) admitted to the paediatric ward for various disorders and 17 healthy family members (age range: 7-40 years; males: 9) of 13 of these children were screened for presence of Helicobacter pylori in the dental plaque by the rapid urease test. H. pylori was detected in dental plaque of 82% (18/22) children and 88% (15/17) of family members. In 85% (28/33) of the positive cases the rapid urease test was positive within 1 hour. Our observations indicate that Helicobacter pylori is present in the dental plaque of majority of children and their family members. PMID- 7883670 TI - Incidence of coxsackie (B) virus infection in diabetics. AB - 45 diabetic patients were screened for raised titres against Coxsackie group of viruses. 11 diabetic patients showed raised titres of neutralising antibodies against one of the coxsackie group of viruses, as against 3 in 25 controls. PMID- 7883671 TI - Delayed hypersensitivity reaction and tuberculosis: review of a hypothesis. PMID- 7883672 TI - Short-term risk factors of coronary artery disease-emerging focus for the 1990s. PMID- 7883673 TI - Severe pulmonary hypertension due to pulmonary thromboembolism following a ventriculo-atrial shunt. PMID- 7883674 TI - An unusual cause for angioneurotic oedema. PMID- 7883675 TI - Pulmonary and cerebral cryptococcosis. PMID- 7883676 TI - Spontaneous rupture of the oesophagus presenting as bilateral pyopneumothorax. PMID- 7883677 TI - Neuropsychiatric presentations in a case of infective endocarditis. PMID- 7883678 TI - Hand mirror cell variant of acute lymphoblastic leukaemia. PMID- 7883679 TI - Hut lung--a domestically acquired pneumoconiosis. PMID- 7883680 TI - A case of continuous muscle fibre activity. PMID- 7883681 TI - Recurrent massive pleural effusion after esophageal variceal sclerotherapy. PMID- 7883682 TI - Angiofollicular lymphoid hyperplasia presenting as POEMS syndrome. PMID- 7883683 TI - Holter monitoring in chronic renal failure before and during dialysis. PMID- 7883684 TI - Platelet hyperactivity in bronchial asthma. PMID- 7883686 TI - Continuous arteriovenous haemofiltration & haemodialysis. PMID- 7883685 TI - Incidence of intracavitary thrombus in dilated cardiomyopathy. PMID- 7883687 TI - Whose area of speciality is this? PMID- 7883688 TI - Ciprofloxacin induced Stevens-Johnson syndrome. PMID- 7883689 TI - Sodium azide--a rare poisoning. PMID- 7883690 TI - Antianginal and cardiopretective effects of terminalia arjuna. PMID- 7883691 TI - Case of cerebral malaria presenting as subarachnoid haemorrhage. PMID- 7883692 TI - Look into your cholesterol. PMID- 7883693 TI - Antianginal and cardiopretective effects of terminalia arjuna. PMID- 7883694 TI - Recommending antibiotics for serious infections after in vitro studies. PMID- 7883695 TI - Does quiniodochlor have bile--acid binding properties? PMID- 7883696 TI - Need to revive intravenous iron infusion therapy. PMID- 7883697 TI - Multidomain architecture of beta-glycosyl transferases: implications for mechanism of action. PMID- 7883698 TI - Control of transcription termination by an RNA factor in bacteriophage P4 immunity: identification of the target sites. AB - Prophage P4 immunity is elicited by a short, 69-nucleotide RNA (CI RNA) coded for within the untranslated leader region of the same operon it controls. CI RNA causes termination of transcription that starts at the promoter PLE and prevents the expression of the distal part of the operon that codes for P4 replication functions (alpha operon). In this work, we identify two sequences in the untranslated leader region of the alpha operon, seqA and seqC, that are the targets of the P4 immunity factor. seqA and seqC exhibit complementarity to a sequence internal to the CI RNA (seqB). Mutations in either seqA or seqC that alter its complementarity to seqB abolished or reduced P4 lysogenization proficiency and delayed the shutoff of the long transcripts originating from PLE that cover the entire operon. Both seqA and seqC single mutants were still sensitive to P4 prophage immunity, whereas P4 seqA seqC double mutants showed a virulent phenotype. Thus, both functional sites are necessary to establish immunity upon infection, whereas a single site appears to be sufficient to prevent lytic gene expression when immunity is established. A mutation in seqB that restored complementarity to both seqA and seqC mutations also restored premature termination of PLE transcripts, thus suggesting an important role for RNA-RNA interactions between seqB and seqA or seqC in P4 immunity. PMID- 7883700 TI - Molecular and expression analysis of the Rhizobium meliloti phosphoenolpyruvate carboxykinase (pckA) gene. AB - The pckA gene of Rhizobium meliloti, encoding phosphoenolpyruvate carboxykinase, was isolated from a genomic cosmid library by complementation of the succinate growth phenotype of a Pck- mutant. The gene region was mapped by subcloning and Tn5 insertion mutagenesis. The DNA sequence for a 2-kb region containing the structural gene and its promoter was determined. The pckA gene encodes as 536 amino-acid protein that shows homology with other ATP-dependent Pck enzymes. The promoter was identified following primer extension analysis and is similar to sigma 70-like promoters. Expression analysis with a pckA::lacZ gene fusion indicated that the pckA gene was strongly induced at the onset of stationary phase in complex medium. When defined carbon sources were tested, the expression level of the pckA gene was found to be high when cells were grown in minimal media with succinate or arabinose as the sole carbon source but almost absent when glucose, sucrose, or glycerol was the sole carbon source. Glucose and sucrose were not found to strongly repress pckA induction by succinate. PMID- 7883701 TI - The end of the cob operon: evidence that the last gene (cobT) catalyzes synthesis of the lower ligand of vitamin B12, dimethylbenzimidazole. AB - The cob operon of Salmonella typhimurium includes 20 genes devoted to the synthesis of adenosyl-cobalamin (coenzyme B12). Mutants with lesions in the promoter-distal end of the operon synthesize vitamin B12 only if provided with 5,6-dimethylbenzimidazole (DMB), the lower ligand of vitamin B12. In the hope of identifying a gene(s) involved in synthesis of DMB, the DNA base sequence of the end of the operon has been determined; this completes the sequence of the cob operon. The cobT gene is the last gene in the operon. Four CobII (DMB-) mutations mapping to different deletion intervals of the CobII region were sequenced; all affect the cobT open reading frame. Both the CobT protein of S. typhimurium and its Pseudomonas homolog have been shown in vitro to catalyze the transfer of ribose phosphate from nicotinate mononucleotide to DMB. This reaction does not contribute to DMB synthesis but rather is the first step in joining DMB to the corrin ring compound cobinamide. Thus, the phenotype of Salmonella cobT mutants conflicts with the reported activity of the affected enzyme, while Pseudomonas mutants have the expected phenotype. J. R. Trzebiatowski, G. A. O'Toole, and J. C. Escalante Semerena have suggested (J. Bacteriol. 176:3568-3575, 1994) that S. typhimurium possesses a second phosphoribosyltransferase activity (CobB) that requires a high concentration of DMB for its activity. We support that suggestion and, in addition, provide evidence that the CobT protein catalyzes both the synthesis of DMB and transfer of ribose phosphate. Some cobT mutants appear defective only in DMB synthesis, since they grow on low levels of DMB and retain their CobII phenotype in the presence of a cobB mutation. Other mutants including those with deletions, appear defective in transferase, since they require a high level of DMB (to activate CobB) and, in combination with a cobB mutation, they eliminate the ability to join DMB and cobinamide. Immediately downstream of the cob operon is a gene (called ORF in this study) of unknown function whose mutants have no detected phenotype. Just counterclockwise of ORF is an asparagine tRNA gene (probably asnU). Farther counterclockwise, a serine tRNA gene (serU or supD) is weakly cotransducible with the cobT gene. PMID- 7883699 TI - Regulation of the hemA gene during 5-aminolevulinic acid formation in Pseudomonas aeruginosa. AB - The general tetrapyrrole precursor 5-aminolevulinic acid is formed in bacteria via two different biosynthetic pathways. Members of the alpha group of the proteobacteria use 5-aminolevulinic acid synthase for the condensation of succinyl-coenzyme A and glycine, while other bacteria utilize a two-step pathway from aminoacylated tRNA(Glu). The tRNA-dependent pathway, involving the enzymes glutamyl-tRNA reductase (encoded by hemA) and glutamate-1-semialdehyde-2,1 aminomutase (encoded by hemL), was demonstrated to be used by Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas stutzeri, Comamonas testosteroni, Azotobacter vinelandii, and Acinetobacter calcoaceticus. To study the regulation of the pathway, the glutamyl-tRNA reductase gene (hemA) from P. aeruginosa was cloned by complementation of an Escherichia coli hemA mutant. The hemA gene was mapped to the SpeI A fragment and the DpnIL fragment of the P. aeruginosa chromosome corresponding to min 24.1 to 26.8. The cloned hemA gene, coding for a protein of 423 amino acids with a calculated molecular mass of 46,234 Da, forms an operon with the gene for protein release factor 1 (prf1). This translational factor mediates the termination of the protein chain at the ribosome at amber and ochre codons. Since the cloned hemA gene did not possess one of the appropriate stop codons, an autoregulatory mechanism such as that postulated for the enterobacterial system was ruled out. Three open reading frames of unknown function transcribed in the opposite direction to the hemA gene were found. hemM/orf1 and orf2 were found to be homologous to open reading frames located in the 5' region of enterobacterial hemA genes. Utilization of both transcription start sites was changed in a P. aeruginosa mutant missing the oxygen regulator Anr (Fnr analog), indicating the involvement of the transcription factor in hemA expression. DNA sequences homologous to one half of an Anr binding site were detected at one of the determined transcription start sites. PMID- 7883702 TI - Cell surface display of recombinant proteins on Staphylococcus carnosus. AB - A novel expression system for surface display of heterologous proteins on Staphylococcus carnosus cells has been developed. Taking advantage of the promoter and secretion signals, including a propeptide region, from the lipase gene of Staphylococcus hyicus and the cell wall-spanning and membrane-binding region of protein A from Staphylococcus aureus, efficient surface display of an 80-amino-acid peptide from a malaria blood stage antigen could be achieved. A serum albumin binding protein from streptococcal protein G was used both as a general reporter molecule and to increase the accessibility of the surface displayed proteins. Immunoblotting, immunogold staining, and immunofluorescence on intact recombinant S. carnosus cells verified the presence of the propeptide, the malaria antigen, and the albumin-binding reporter protein on the bacterial surface. For the first time, fluorescence-activated cell sorting was used to analyze the presence of surface-displayed hybrid receptors on gram-positive bacteria. PMID- 7883703 TI - The Escherichia coli G-fimbrial lectin protein participates both in fimbrial biogenesis and in recognition of the receptor N-acetyl-D-glucosamine. AB - The gafD gene encoding the N-acetyl-D-glucosamine-specific fimbrial lectin (adhesin) protein GafD of uropathogenic Escherichia coli was cloned and subjected to genetic analysis. The corresponding gene product was isolated as a MalE fusion protein. The lectin gene was identified with the aid of deletion mutagenesis; mutations in gafD impaired either receptor binding or both receptor binding and fimbria production, depending on the mutation created. All mutants converted to wild-type expressors when complemented in trans with the cloned intact gafD gene. The predicted 354-amino-acid sequence of GafD, deduced from the nucleotide sequence, is closely related to those of the fimbria-associated F17-G and F17b-G proteins coded for by enterotoxigenic and invasive E. coli strains. Isolated GafD was shown to recognize N-acetyl-D-glucosamine by virtue of specific binding to an immobilized receptor, thus proving directly that GafD is a sugar-binding protein. Our results indicate that GafD as such is sufficient for receptor recognition and that the protein also participates in fimbrial biogenesis. PMID- 7883704 TI - Aromatic effector activation of the NtrC-like transcriptional regulator PhhR limits the catabolic potential of the (methyl)phenol degradative pathway it controls. AB - Pseudomonas putida P35X (NCIB 9869) metabolizes phenol and monomethylphenols via a chromosomally encoded meta-cleavage pathway. We have recently described a 13.4 kb fragment of the chromosome that codes for the first eight genes of the catabolic pathway and a divergently transcribed positive regulator, phhR. The eight structural genes lie in an operon, the phh operon, downstream of a -24 TGGC, -12 TTGC promoter sequence. Promoters of this class are recognized by RNA polymerase that utilizes the alternative sigma 54 factor encoded by rpoN (ntrA) and are positively regulated by activators of the NtrC family. In this study, we have identified the coding region for the 63-kDa PhhR gene product by nucleotide sequencing of a 2,040-bp region and polypeptide analysis. PhhR was found to have homology with the NtrC family of transcriptional activators, in particular with DmpR, the pVI150-encoded regulator of (methyl)phenol catabolism by Pseudomonas sp. strain CF600. By using a luciferase reporter system, PhhR alone was shown to be sufficient to activate transcription from the phh operon promoter in an RpoN+ background but not an RpoN- background. Luciferase reporter systems were also used to directly compare the aromatic effector profiles of PhhR and DmpR. Evidence that the difference in the growth substrate ranges of strains P35X and CF600 is due to the effector activation specificities of the regulators of these systems rather than the substrate specificities of the catabolic enzymes is presented. PMID- 7883705 TI - Identification of endo-beta-N-acetylglucosaminidase and N-acetylmuramyl-L-alanine amidase as cluster-dispersing enzymes in Staphylococcus aureus. AB - Two proteins which are capable of dispersing cell clusters of Staphylococcus aureus have been purified from a S. aureus FDA209P culture supernatant. Both of them were found to have bacteriolytic activity. From the elution profile of column chromatography and Western blot (immunoblot) analysis, one of them was identified as a 51-kDa endo-beta-N-acetylglucosaminidase (GL). The other was a 62 kDa protein on the basis of sodium dodecyl sulfate gel electrophoresis. Analysis of the peptidoglycan fragments following treatment with the 62-kDa protein indicated that this protein is an N-acetylmuramyl-L-alanine amidase (AM). In vitro studies of cluster dispersion activities using S. aureus mutant strains Lyt66 or S. aureus Wood46 grown as clusters demonstrated that these two enzymes act synergistically to disperse clusters into single cells. Antiserum against the 51-kDa GL cross-reacted with the 62-kDa AM, and S. aureus FDA209P grown in the presence of anti-51-kDa-GL immunoglobulin G induced giant clusters. Clusters induced by anti-51-kDa GL and by Cibacron blue F3G-A were dispersed by coincubation with the 51-kDa GL and the 62-kDa AM. Western blot analysis demonstrated that the 51-kDa GL and the 62-kDa AM were missing in culture supernatants of S. aureus Lyt66, Wood46, and RUSAL2 (Tn551 autolysin-defective mutant), which grow in clusters. These results strongly suggest that the 51-kDa GL and 62-kDa AM are involved in cell separation of daughter cells after cell division. PMID- 7883706 TI - Gratuitous overexpression of genes in Escherichia coli leads to growth inhibition and ribosome destruction. AB - We attempted to test the idea that the relative abundance of each individual tRNA isoacceptor in Escherichia coli can be altered by varying its cognate codon concentration. In order to change the overall codon composition of the messenger pool, we have expressed in E. coli lacZ with the aid of T7 RNA polymerase so that their respective gene products individually accounted for 30% of the total bacterial protein. Unexpectedly, the maximum expression of either test gene has no specific effect on the relative rates of synthesis of the tRNA species that we studied. Instead, we find that there is a cumulative breakdown of rRNAs, which results in a loss of ribosomes and protein synthetic capacity. After either of the test genes is maximally induced, there is a growing fraction of protein synthesis invested in beta-galactosidase or delta tufB that is matched by a comparable decrease of the fraction of normal protein synthesis. We have also observed enhanced accumulation of two heat shock proteins during overexpression. Finally, after several hours of overexpression of either test protein, the bacteria are no longer viable. These results are relevant to the practical problems of obtaining high expression levels for cloned proteins. PMID- 7883707 TI - The genes encoding the delta subunits of dinitrogenases 2 and 3 are required for mo-independent diazotrophic growth by Azotobacter vinelandii. AB - vnfG and anfG encode the delta subunits of alternative nitrogenases 2 and 3 in Azotobacter vinelandii, respectively. As a first step towards elucidating the role of these subunits, diazotrophic growth and acetylene reduction studies were conducted on mutants containing alterations in the genes encoding these subunits. Mutants containing a stop codon (C36stop) or an in-frame deletion in anfG were unable to grow in N-free, Mo-deficient medium (Anf-). Mutants in which cysteine 36 of AnfG (a residue conserved between VnfG and AnfG) was changed to Ala or Ser were Anf+. Thus, this conserved cysteine is not essential for the function of AnfG in dinitrogenase 3. A mutant with a stop codon in vnfG (C17stop) grew after a lag of 25 h in N-free, Mo-deficient medium containing V2O5. However, a Nif- Anf strain with this mutation was unable to grow under these conditions. This shows that the vnfG gene product is required for nitrogenase 2-dependent growth. Strains with mutations in vnfG and anfG reduced acetylene to different degrees. This indicates that the delta subunits are not required for acetylene reduction by nitrogenases 2 and 3. PMID- 7883708 TI - Construction and characterization of mutants of Salmonella typhimurium deficient in DNA repair of O6-methylguanine. AB - Escherichia coli has two O6-methylguanine DNA methyltransferases that repair alkylation damage in DNA and are encoded by the ada and ogt genes. The ada gene of E. coli also regulates the adaptive response to alkylation damage. The closely related species Salmonella typhimurium possesses methyltransferase activities but does not exhibit an adaptive response conferring detectable resistance to mutagenic methylating agents. We have previously cloned the ada-like gene of S. typhimurium (adaST) and constructed an adaST-deletion derivative of S. typhimurium TA1535. Unexpectedly, the sensitivity of the resulting strain to the mutagenic action of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was similar to that of the parent strain. In this study, we have cloned and sequenced the ogt like gene of S. typhimurium (ogtST) and characterized ogtST-deletion derivatives of TA1535. The ogtST mutant was more sensitive than the parent strain to the mutagenicity of MNNG and other simple alkylating agents with longer alkyl groups (ethyl, propyl, and butyl). The adaST-ogtST double mutant had a level of hypersensitivity to these agents similar to that of the ogtST single mutant. The ogtST and the adaST-ogtST mutants also displayed a two to three times higher spontaneous mutation frequency than the parent strain and the adaST mutant. These results indicate that the OgtST protein, but not the AdaST protein, plays a major role in protecting S. typhimurium from the mutagenic action of endogenous as well as exogenous alkylating agents. PMID- 7883709 TI - A short-filament mutant of Anabaena sp. strain PCC 7120 that fragments in nitrogen-deficient medium. AB - Strain 129 is a fragmentation mutant of the filamentous cyanobacterium Anabaena sp. strain PCC 7120. Growing with fixed nitrogen, this mutant forms filaments that are much shorter than wild-type filaments. Following starvation for fixed nitrogen, strain 129 becomes nearly unicellular and forms few heterocysts, although electron microscopy suggests that proheterocysts form while fragmentation occurs. Starvation for sulfate, phosphate, iron, and calcium does not cause this fragmentation. The affected gene in strain 129, fraC, was cloned by complementation and characterized. It encodes a unique 179-amino-acid protein rich in phenylalanine. Insertional inactivation of the chromosomal copy of fraC results in a phenotype identical to that of strain 129, while complementation using a truncated version of FraC results in only partial complementation of the original mutant. Heterocysts could be induced to form in N-replete cultures of strain 129, as in wild-type cells, by supplying extra copies of the hetR gene on a plasmid. Thus, FraC is required for the integrity of cell junctions in general but is apparently not directly involved in normal differentiation and nitrogen fixation. PMID- 7883710 TI - New beta-glucoside (bgl) genes in Bacillus subtilis: the bglP gene product has both transport and regulatory functions similar to those of BglF, its Escherichia coli homolog. AB - The Bacillus subtilis sacY and sacT genes encode antiterminator proteins, similar to the Escherichia coli bglG gene product and required for transcription of sucrose metabolism genes. A Tn10 insertion into bglP (formerly sytA) has been previously identified as restoring sucrose utilization to a strain with deletions of both sacY and sacT. The nucleotide sequence of bglP showed a high degree of homology with the E. coli bglF gene (BglF is a beta-glucoside permease of the phosphotransferase system and also acts as a negative regulator of the BglG antiterminator). Complementation studies of an E. coli strain with a deletion of the bgl operon showed that BglP was a functional beta-glucoside permease. In B. subtilis, bglP complemented in trans both the bglP::Tn10 original insertion and a phenotypically similar bglP deletion. Disruption of licT abolished the suppressor phenotype in a bglP mutant. LicT is a recently identified third B. subtilis antiterminator of the BglG/SacY family. These observations indicated that BglP was also a negative regulator of LicT. Both LicT and BglP seem to be involved in the induction by beta-glucosides of an operon containing at least two genes, bglP itself and bglH, encoding a phospho-beta-glucosidase. Other beta-glucoside genes homologous to bglP and bglH have been recently described in B. subtilis. Thus, B. subtilis possesses several sets of beta-glucoside genes, like E. coli, but these genes do not appear to be cryptic. PMID- 7883711 TI - bfr1+, a novel gene of Schizosaccharomyces pombe which confers brefeldin A resistance, is structurally related to the ATP-binding cassette superfamily. AB - We have isolated a Schizosaccharomyces pombe gene, bfr1+, which on a multicopy plasmid vector, pDB248', confers resistance to brefeldin A (BFA), an inhibitor of intracellular protein transport. This gene encodes a novel protein of 1,531 amino acids with an intramolecular duplicated structure, each half containing a single ATP-binding consensus sequence and a set of six transmembrane sequences. This structural characteristic of bfr1+ protein resembles that of mammalian P glycoprotein, which, by exporting a variety of anticancer drugs, has been shown to be responsible for multidrug resistance in tumor cells. Consistent with this is that S. pombe cells harboring bfr1+ on pDB248' are resistant to actinomycin D, cerulenin, and cytochalasin B, as well as to BFA. The relative positions of the ATP-binding sequences and the clusters of transmembrane sequences within the bfr1+ protein are, however, transposed in comparison with those in P glycoprotein; the bfr1+ protein has N-terminal ATP-binding sequence followed by transmembrane segments in each half of the molecule. The bfr1+ protein exhibited significant homology in primary and secondary structures with two recently identified multidrug resistance gene products of Saccharomyces cerevisiae, Snq2 and Sts1/Pdr5/Ydr1. The bfr1+ gene is not essential for cell growth or mating, but a delta bfr1 mutant exhibited hypersensitivity to BFA. We propose that the bfr1+ protein is another member of the ATP-binding cassette superfamily and serves as an efflux pump of various antibiotics. PMID- 7883712 TI - Molecular cloning and nucleotide sequence of the gene encoding the major peptidoglycan hydrolase of Lactococcus lactis, a muramidase needed for cell separation. AB - A gene of Lactococcus lactis subsp. cremoris MG1363 encoding a peptidoglycan hydrolase was identified in a genomic library of the strain in pUC19 by screening Escherichia coli transformants for cell wall lysis activity on a medium containing autoclaved, lyophilized Micrococcus lysodeikticus cells. In cell extracts of L. lactis MG1363 and several halo-producing E. coli transformants, lytic bands of similar sizes were identified by denaturing sodium dodecyl sulfate (SDS)-polyacrylamide gels containing L. lactis or M. lysodeikticus cell walls. Of these clearing bands, corresponding to the presence of lytic enzymes with sizes of 46 and 41 kDa, the 41-kDa band was also present in the supernatant of an L. lactis culture. Deletion analysis of one of the recombinant plasmids showed that the information specifying lytic activity was contained within a 2,428-bp EcoRV Sau3A fragment. Sequencing of part of this fragment revealed a gene (acmA) that could encode a polypeptide of 437 amino acid residues. The calculated molecular mass of AcmA (46,564 Da) corresponded to that of one of the lytic activities detected. Presumably, the enzyme is synthesized as a precursor protein which is processed by cleavage after the Ala at position 57, thus producing a mature protein with a size of 40,264 Da, which would correspond to the size of the enzyme whose lytic activity was present in culture supernatants of L. lactis. The N-terminal region of the mature protein showed 60% identity with the N-terminal region of the mature muramidase-2 of Enterococcus hirae and the autolysin of Streptococcus faecalis. Like the latter two enzymes, AcmA contains C-terminal repeated regions. In AcmA, these three repeats are separated by nonhomologous intervening sequences highly enriched in serine, threonine, and asparagine. Genes specifying identical activities were detected in various strains of L. lactis subsp. lactis and L. lactis subsp. cremoris by the SDS-polyacrylamide gel electrophoresis detection assay and PCR experiments. By replacement recombination, an acmA deletion mutant which grew as long chains was constructed, indicating that AcmA is required for cell separation. PMID- 7883714 TI - Characterization of nifB, nifS, and nifU genes in the cyanobacterium Anabaena variabilis: NifB is required for the vanadium-dependent nitrogenase. AB - Anabaena variabilis ATCC 29413 is a heterotrophic, nitrogen-fixing cyanobacterium containing both a Mo-dependent nitrogenase encoded by the nif genes and V dependent nitrogenase encoded by the vnf genes. The nifB, nifS, and nifU genes of A. variabilis were cloned, mapped, and partially sequenced. The fdxN gene was between nifB and nifS. Growth and acetylene reduction assays using wild-type and mutant strains indicated that the nifB product (NifB) was required for nitrogen fixation not only by the enzyme encoded by the nif genes but also by the enzyme encoded by the vnf genes. Neither NifS nor NifU was essential for nitrogen fixation in A. variabilis. PMID- 7883713 TI - Cloning, sequencing, and expression of the uroporphyrinogen III methyltransferase cobA gene of Propionibacterium freudenreichii (shermanii). AB - We cloned, sequenced, and overexpressed cobA, the gene encoding uroporphyrinogen III methyltransferase in Propionibacterium freudenreichii, and examined the catalytic properties of the enzyme. The methyltransferase is similar in mass (27 kDa) and homologous to the one isolated from Pseudomonas denitrificans. In contrast to the much larger isoenzyme encoded by the cysG gene of Escherichia coli (52 kDa), the P. freudenreichii enzyme does not contain the additional 22 kDa peptide moiety at its N-terminal end bearing the oxidase-ferrochelatase activity responsible for the conversion of dihydrosirohydrochlorin (precorrin-2) to siroheme. Since it does not contain this moiety, it is not a likely candidate for synthesis of a cobalt-containing early intermediate that has been proposed for the vitamin B12 biosynthetic pathway in P. freudenreichii. Uroporphyrinogen III methyltransferase of P. freudenreichii not only catalyzes the addition of two methyl groups to uroporphyrinogen III to afford the early vitamin B12 intermediate, precorrin-2, but also has an overmethylation property that catalyzes the synthesis of several tri- and tetra-methylated compounds that are not part of the vitamin B12 pathway. The enzyme catalyzes the addition of three methyl groups to uroporphyrinogen I to form trimethylpyrrocorphin, the intermediate necessary for biosynthesis of the natural products, factors S1 and S3, previously isolated from this organism. A second gene found upstream from the cobA gene encodes a protein homologous to CbiO of Salmonella typhimurium, a membrane-bound, ATP-dependent transport protein thought to be part of the cobalt transport system involved in vitamin B12 synthesis. These two genes do not appear to constitute part of an extensive cobalamin operon. PMID- 7883716 TI - Widespread protein sequence similarities: origins of Escherichia coli genes. AB - To learn more about the evolutionary origins of Escherichia coli genes, we surveyed systematically for extended sequence similarities among the 1,264 amino acid sequences encoded by chromosomal genes of E. coli K-12 in SwissProt release 26 by using the FASTA program and imposing the following criteria: (i) alignment of segments at least 100 amino acids long and (ii) at least 20% amino acid identity. Altogether, 624 extended alignments meeting the two criteria were identified, corresponding to 577 protein sequences (45.6% of the 1,264 E. coli protein sequences) that had an extended alignment with at least one other E. coli protein sequence. To exclude alignments of questionable biological significance, we imposed a high threshold on the number of gaps allowed in each of the 624 extended alignments, giving us a subset of 464 proteins. The population of 464 alignments has the following characteristics expressed as median values of the group: 254 amino acids in the alignment, representing 86% of the length of the protein, 33% of the amino acids in the alignment being identical, and 1.1 gaps introduced per 100 amino acids of alignment. Where functions are known, nearly all pairs consist of functionally related proteins. This implies that the sequence similarity we detected has biological meaning and did not arise by chance. That a major fraction of E. coli proteins form extended alignments strongly suggests the predominance of duplication and divergence of ancestral genes in the evolution of E. coli genes. The range of degrees of similarity shows that some genes originated more recently than others. There is no evidence of genome doubling in the past, since map distances between genes of sequence related proteins show no coherent pattern of favored separations. PMID- 7883715 TI - Imidazole acetol phosphate aminotransferase in Zymomonas mobilis: molecular genetic, biochemical, and evolutionary analyses. AB - hisH encodes imidazole acetol phosphate (IAP) aminotransferase in Zymomonas mobilis and is located immediately upstream of tyrC, a gene which codes for cyclohexadienyl dehydrogenase. A plasmid containing hisH was able to complement an Escherichia coli histidine auxotroph which lacked the homologous aminotransferase. DNA sequencing of hisH revealed an open reading frame of 1,110 bp, encoding a protein of 40,631 Da. The cloned hisH product was purified from E. coli and estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to have a molecular mass of 40,000 Da. Since the native enzyme had a molecular mass of 85,000 Da as determined by gel filtration, the active enzyme species must be a homodimer. The purified enzyme was able to transaminate aromatic amino acids and histidine in addition to histidinol phosphate. The existence of a single protein having broad substrate specificity was consistent with the constant ratio of activities obtained with different substrates following a variety of physical treatments (such as freeze-thaw, temperature inactivation, and manipulation of pyridoxal 5'-phosphate content). The purified enzyme did not require addition of pyridoxal 5'-phosphate, but dependence upon this cofactor was demonstrated following resolution of the enzyme and cofactor by hydroxylamine treatment. Kinetic data showed the classic ping-pong mechanism expected for aminotransferases. Km values of 0.17, 3.39, and 43.48 mM for histidinol phosphate, tyrosine, and phenylalanine were obtained. The gene structure around hisH-tyrC suggested an operon organization. The hisH-tyrC cluster in Z. mobilis is reminiscent of the hisH-tyrA component of a complex operon in Bacillus subtilis, which includes the tryptophan operon and aroE. Multiple alignment of all aminotransferase sequences available in the database showed that within the class I superfamily of aminotransferases, IAP aminotransferases (family I beta) are closer to the I gamma family (e.g., rat tyrosine aminotransferase) than to the I alpha family (e.g., rat aspartate aminotransferase or E. coli AspC). Signature motifs which distinguish the IAP aminotransferase family were identified in the region of the active-site lysine and in the region of the interdomain interface. PMID- 7883717 TI - Streptomycin- and rifampin-resistant mutants of Escherichia coli perturb F exclusion of bacteriophage T7 by affecting synthesis of the F plasmid protein PifA. AB - Certain alleles of rpsL that confer resistance to the antibiotic streptomycin almost completely relieve F exclusion of bacteriophage T7. Introduction of a specific rpoB allele conferring resistance to rifampin into the rpsL strain restores the ability of the F-containing strain to exclude T7. This variation in the severity of F exclusion is reflected in the levels of the F-encoded inhibitor protein PifA: F'-containing cells that harbor specific rpsL alleles are phenotypically Pif-, but become Pif+ by the further acquisition of a specific rpoB allele. F-containing cells harboring the gyrA43(Ts) mutation also appear phenotypically Pif-, possibly because repression of the pif operon is enhanced by an altered DNA conformation in the gyrase mutant strain. PMID- 7883719 TI - A mutant phosphoenolpyruvate carboxykinase in Escherichia coli conferring oxaloacetate decarboxylase activity. AB - The phosphoenolpyruvate carboxykinase in Escherichia coli (encoded by pck) catalyzes the conversion from oxaloacetate (OAA) to phosphoenolpyruvate under gluconeogenic conditions. We report here the characterization of two mutant alleles, pck-51 and pck-53, both of which are point mutations leading to single amino acid changes (D to N at position 268 and G to S at position 284, respectively). Pck51 is an altered-activity mutant that catalyzes the conversion from OAA to pyruvate (OAA decarboxylase activity). This new activity was not detected from the wild-type Pck, and it complements the pck null mutation only in a pps+ background. Pck53 is a reduced-activity mutant that complements the pck null mutation in a strain-dependent fashion. PMID- 7883718 TI - Genetic and molecular characterization of the polar flagellum of Vibrio parahaemolyticus. AB - Vibrio parahaemolyticus possesses two alternate flagellar systems adapted for movement under different circumstances. A single polar flagellum propels the bacterium in liquid (swimming), while multiple lateral flagella move the bacterium over surfaces (swarming). Energy to rotate the polar flagellum is derived from the sodium membrane potential, whereas lateral flagella are powered by the proton motive force. Lateral flagella are arranged peritrichously, and the unsheathed filaments are polymerized from a single flagellin. The polar flagellum is synthesized constitutively, but lateral flagella are produced only under conditions in which the polar flagellum is not functional, e.g., on surfaces. This work initiates characterization of the sheathed, polar flagellum. Four genes encoding flagellins were cloned and found to map in two loci. These genes, as well as three genes encoding proteins resembling HAPs (hook-associated proteins), were sequenced. A potential consensus polar flagellar promoter was identified by using upstream sequences from seven polar genes. It resembled the enterobacterial sigma 28 consensus promoter. Three of the four flagellin genes were expressed in Escherichia coli, and expression was dependent on the product of the fliA gene encoding sigma 28. The fourth flagellin gene may be different regulated. It was not expressed in E. coli, and inspection of upstream sequence revealed a potential sigma 54 consensus promoter. Mutants with single and multiple defects in flagellin genes were constructed in order to determine assembly rules for filament polymerization. HAP mutants displayed new phenotypes, which were different from those of Salmonella typhimurium and most probably were the result of the filament being sheathed. PMID- 7883721 TI - A reassessment of the relationship between aroK- and aroL-encoded shikimate kinase enzymes of Escherichia coli. AB - In the course of sequencing the aroK gene, a number of errors were found in the published sequence. The corrected sequence alters the length of the aroK coding region such that the AroK and AroL proteins are now of comparable length and the homology between them extends the entire length of the two enzymes. PMID- 7883720 TI - The amino acid sequence of Lrp is highly conserved in four enteric microorganisms. AB - Lrp (leucine-responsive regulatory protein) is a global regulator of metabolism in Escherichia coli (J. M. Calvo and R. G. Matthews, Microbiol. Rev. 58:466-490, 1994). The lrp genes from three other enteric microorganisms, Enterobacter aerogenes, Klebsiella aerogenes, and Salmonella typhimurium, were cloned and sequenced. An analysis of these sequences and of the previously determined sequence from E. coli indicated that the vast majority of changes were synonymous rather than nonsynonymous changes. Nucleotide changes occurred at 89 of 492 positions but resulted in amino acid changes at only 2 of 164 positions. This analysis suggests that the Lrp amino acid sequence is highly adapted for function and that almost all amino acid changes lead to a protein that functions less well than the wild-type protein. PMID- 7883722 TI - Identification of a Bacillus subtilis spo0H allele that is necessary for suppression of the sporulation-defective phenotype of a spo0A mutation. AB - A mutation in Bacillus subtilis spo0A codon 97 suppressed the sporulation defect caused by the spo0A9V mutation. The suppressor activity of the codon 97 mutation was evident only in the presence of a novel spo0H allele. Our results suggest that the spo0A gene product interacts with the sigma factor subunit of RNA polymerase. PMID- 7883723 TI - Genetic evidence that PpsR from Rhodobacter sphaeroides 2.4.1 functions as a repressor of puc and bchF expression. AB - The ppsR gene (R. J. Penfold and J. M. Pemberton, J. Bacteriol. 176:2869-2876, 1994) from Rhodobacter sphaeroides 2.4.1 functions as a transcriptional repressor of puc and bchF expression. The carboxy terminus of PpsR, containing the putative DNA-binding domain, by itself possesses repressor activity. Intact palindromes having the motif TGT-N12-ACA are required for PpsR activity. PMID- 7883724 TI - Distribution of the CorA Mg2+ transport system in gram-negative bacteria. AB - The CorA Mg2+ transport system is the dominant constitutive uptake mechanism in Salmonella typhimurium and Escherichia coli. Southern blot hybridization and PCR techniques were used to screen a panel of 18 additional gram-negative bacterial species for corA homologs. Virtually all strains tested positive for the presence of corA. Thus, corA appears to be ubiquitous within gram-negative bacteria and is likely their major Mg2+ influx system. PMID- 7883725 TI - Exoglucanase activities of the recombinant Clostridium thermocellum CelS, a major cellulosome component. AB - The recombinant CelS (rCelS), the most abundant catalytic subunit of the Clostridium thermocellum cellulosome, displayed typical exoglucanase characteristics, including (i) a preference for amorphous or crystalline cellulose over carboxymethyl cellulose, (ii) an inability to reduce the viscosity of a carboxymethyl cellulose solution, and (iii) the production of few bound reducing ends on the solid substrate. The hydrolysis products from crystalline cellulose were cellobiose and cellotriose at a ratio of 5:1. The rCelS activity on amorphous cellulose was optimal at 70 degrees C and at pH 5 to 6. Its thermostability was increased by Ca2+. Sulfhydryl reagents had only a mild adverse effect on the rCelS activity. Cellotetraose was the smallest oligosaccharide substrate for rCelS, and the hydrolysis rate increased with the substrate chain length. Many of these properties were consistent with those of the cellulosome, indicating a key role for CelS. PMID- 7883726 TI - Modulation of the allosteric equilibrium of yeast chorismate mutase by variation of a single amino acid residue. AB - Chorismate mutase (EC 5.4.99.5) from the yeast Saccharomyces cerevisiae is an allosteric enzyme which can be locked in its active R (relaxed) state by a single threonine-to-isoleucine exchange at position 226. Seven new replacements of residue 226 reveal that this position is able to direct the enzyme's allosteric equilibrium, without interfering with the catalytic constant or the affinity for the activator. PMID- 7883727 TI - The effects of race on diagnosis and disposition from a psychiatric emergency service. AB - BACKGROUND: Previous studies have reported that racial differences exist in patterns of clinical psychiatric diagnoses as well as the distribution of mental health services resources. The psychiatric emergency service serves as an entry point into the mental health system, so it plays a potentially important role in addressing racial disparities in diagnosis and disposition. To address this disparity, the authors studied two specific questions: (1) are there racial differences in diagnosis and (2) are there racial differences in disposition of patients visiting a psychiatric emergency service? METHOD: Demographic and clinical data were obtained by retrospective chart review of 490 patients randomly selected from 9500 visits to a large psychiatric emergency service during a 1-year period. All clinical information had been recorded by the primary treaters who had no knowledge of this study. RESULTS: Black patients were significantly more likely to be diagnosed with schizophrenia and substance abuse than similar white patients, although less likely to be diagnosed with a personality disorder. Black patients were significantly more likely to be hospitalized, particularly at a public hospital, although there were no significant differences in insurance coverage or measures of suicidal or homicidal ideation. CONCLUSION: Despite the availability of DSM-III-R criteria, black patients continue to be disproportionately diagnosed with schizophrenia. In this sample, this diagnosis may have been given in lieu of a personality disorder or affective illness diagnosis. Black patients are also more likely to be hospitalized. These observations suggest that further research is needed to clarify the effects of race on the decision-making process in diagnosis and disposition from the psychiatric emergency service. PMID- 7883728 TI - Is clozapine a mood stabilizer? AB - BACKGROUND: Clozapine has been increasingly shown to be effective in the acute and maintenance treatment of bipolar disorders. For this reason, we studied whether clozapine alone is effective as a mood stabilizer in patients with refractory bipolar disorders. METHOD: Subjects were part of a long-term follow-up study cohort of 193 patients with refractory mood disorders who were treated with clozapine at McLean Hospital prior to July 1, 1992. Patients included in this study were those older than 16 years with bipolar disorder (manic or mixed) and schizoaffective disorder, bipolar type, discharged taking clozapine alone (N = 17). Hospital records on all patients were reviewed by trained raters blind to "best-estimate" diagnoses. Response to clozapine was determined by the Clinical Global Impressions-Improvement (CGI-I) scale. Patients were contacted at least 6 months after clozapine initiation for semistructured follow-up interviews by raters blind to diagnosis and baseline information. RESULTS: Seventeen subjects were contacted 16.1 +/- 5.6 months after clozapine initiation. Most of the 17 patients had previously failed trials of lithium, valproate, carbamazepine, neuroleptics, combinations of these, and electroconvulsive therapy; or had tardive dyskinesia. Of these patients, 65% (11/17) continued to be on clozapine therapy alone at follow-up and had no subsequent rehospitalization or affective episode. At follow-up, there was a significant decrease in the rehospitalization rate (p = .025) than before starting clozapine and a significant improvement in CGI-I scores (p = .02). CONCLUSION: Clozapine monotherapy is an effective mood stabilizer, reducing both the number of affective episodes and rehospitalizations in patients with severe refractory bipolar illness. PMID- 7883729 TI - Panic-phobic patients and developmental trauma. AB - BACKGROUND: Several studies suggest high rates of developmental trauma among adult anxiety disorder patients. We attempted to replicate these findings in patients with panic disorder, agoraphobia, and/or social phobia in comparison with a nonclinical population and to evaluate possible relationship of traumas and phobic subtypes. METHOD: Fifty-one patients with panic disorder with agoraphobia and/or social phobia were assessed for lifetime diagnoses using interviews and rating scales and for developmental trauma by the Life Experience Questionnaire (LEQ). Fifty-one demographically similar nonclinical subjects completed a questionnaire that included the LEQ and screening questions for lifetime psychopathology. RESULTS: Childhood trauma was reported by 63% (N = 32) of the patients (vs. 35% or 18 of comparison subjects and 24% or 9 of subjects negative for lifetime psychopathology; chi 2 = 7.7, df = 1, p < .01). Sexual and/or physical abuse histories (and not separation and/or loss) were significantly increased in the patient group and were most specifically associated with social phobia. CONCLUSION: We find a similar, increased rate of childhood trauma as has been reported in previous studies of anxiety disorder patients. In our findings, this most specifically represents an association of social phobia and sexual/physical abuse histories. PMID- 7883730 TI - Valproate in the treatment of acute bipolar affective episodes complicated by substance abuse: a pilot study. AB - BACKGROUND: Bipolar disorder is commonly complicated by comorbid substance dependence. Little is known about treatment of this important subpopulation of patients with bipolar disorder. The following study was designed to preliminary explore the use of valproate in a group of patients with comorbid bipolar disorder and substance dependence. METHOD: Nine patients with bipolar disorder, as defined by DSM-III-R, and concurrent substance dependence (five alcohol, three polysubstance abuse, one cocaine) were treated with valproate in an open-label, nonblinded trial. Subjects were followed for a mean of 16 weeks. Ratings included measures of affective state (Young Mania Rating Scale, Hamilton Rating Scale for Depression [HAM-D]) as well as substance use (Time-Line Follow-Back). RESULTS: Patients tolerated valproate well with minimal reports of side effects and no liver toxicity or increase in liver function tests noted. The mean +/- SD maintenance dose of valproate was 1583 +/- 204 mg/day. Subjects evidenced significant decreases in both depression (HAM-D score 17.8 vs. 10.4, p < or = .005) and mania (Young Mania Rating Scale score 12.0 vs. 4.9, p < or = .001) ratings by Week 4, which were sustained throughout the study period. There was a significant decrease in number of days of substance use (t = 4.7, p < or = .005) as well as the amount of substances used during the follow-up period as compared with the month before valproate treatment. CONCLUSION: While limited by the open label, nonblinded nature of the design, this study provides preliminary evidence for the efficacy of valproate in the acute treatment of bipolar episodes complicated by concomitant substance dependence. The medication was well tolerated, and no unacceptable elevations in liver function tests were seen. PMID- 7883731 TI - Possible serotonin syndrome following the combined administration of clomipramine and alprazolam. PMID- 7883732 TI - Doxepin withdrawal mania. PMID- 7883733 TI - Sertraline treatment of aggression in a developmentally disabled patient. PMID- 7883735 TI - Estimation of the association between desipramine and the risk for sudden death in 5- to 14-year-old children. AB - BACKGROUND: Four cases of sudden death in children 12 years or younger during desipramine treatment were identified between 1986 and 1992. We evaluated whether these events support the hypothesis that exposure to therapeutic doses of desipramine contributes to the risk for sudden death in otherwise healthy children. METHOD: The National Center for Health Statistics provided the baseline number of sudden unexplained deaths in children 5 to 14 years old. Data from the National Disease and Therapeutic Index were used to estimate the exposure to desipramine in children in the same age group. Since two of the four deaths were identified by 1987, we used the post-1987 experience as if it were a prospective period in which a causal association could be examined. RESULTS: The number of sudden deaths in desipramine-exposed children did not increase from 1986 to 1992 despite a marked increase in exposure. By using 4 to 6 months as the average lifetime of a desipramine prescription and a baseline rate of sudden death of 4.2 deaths/million/year in this population, the post-1987 period would account for 162,000 to 242,000 person-years of desipramine exposure. Although not statistically significant, this level of exposure corresponds to a relative risk of 2.1 (95% CI = 0.5 to 15) to 3.1 (95% CI = 0.8 to 22). CONCLUSION: Although, based on our estimates, the evidence for an association between desipramine and sudden death in children aged 5 to 14 years appears weak, replication of our findings is needed with a more precise numerator (total number of deaths) and denominator (the appropriate conversion from drug appearance to actual exposure) before a firm conclusion on this subject can be drawn. Until then, even if remote, the possibility of an association between desipramine and sudden death in children stresses the importance of assessing risks and benefits when desipramine is used in pediatric patients. PMID- 7883734 TI - Treatment of sexual side effects with dopaminergic agents. PMID- 7883736 TI - Assessment of extrapyramidal symptoms during acute neuroleptic treatment. AB - BACKGROUND: Acute administration of traditional neuroleptic drugs is often accompanied by the emergence of extrapyramidal symptoms (EPS). The use of a standardized scale to measure EPS can assist the clinician in assessing the occurrence and severity of these adverse reactions. The current work presents the interrater reliability and validity of the Yale Extrapyramidal Symptom Scale (YESS)--an eight-item, easy-to-administer scale for assessing emergence, severity, and type of side effects that commonly occur during acute treatment. METHOD: Interrater reliability (Study 1) and validity (Study 2) of the scale were studied using two independent samples of acutely psychotic patients treated with neuroleptic drugs. Study 1: Interrater reliability was assessed by comparing the YESS ratings of two clinicians blind to the other's rating and to the patient's drug regimen and dose. Study 2: Validity was studied by examining whether YESS items correlated with other EPS measures (convergent validity) but not with psychotic symptoms that may be confused with EPS (discriminant validity). RESULTS: Interrater agreement between clinicians was good to excellent. YESS items correlated with assessments used to measure symptoms of Parkinson's disease and akathisia and generally showed low nonsignificant correlations with ratings of symptoms of psychosis. CONCLUSION: The current work presents a brief EPS scale for the assessment of commonly occurring neuroleptic-induced extrapyramidal side effects. It was demonstrated that the YESS could be used reliably across clinician raters and that the YESS is a valid measure for assessing EPS during acute treatment. PMID- 7883737 TI - A medication algorithm for treatment of bipolar rapid cycling? AB - Individuals with the rapid cycling form of bipolar disorder represent 13% to 20% of the bipolar population. Although lithium remains the treatment of choice for classic bipolar disorder, failure rates as high as 72% to 82% have been reported for lithium among those who have the rapid cycling variant. Treatment alternatives, including the use of divalproex sodium and carbamazepine, have shown promise for this often treatment-refractory group of patients. Predictors of positive outcome for the acute and prophylactic management of mania with divalproex sodium have emerged; they include nonpsychotic mania, the occurrence of decreasing or stable episode frequencies, mild mania, and mixed states. Predictors for positive acute and prophylactic antidepressant responses to divalproex sodium include nonpsychotic mania, increasingly severe mania, and the absence of borderline personality. Mixed results have been reported for studies using carbamazepine therapy for the treatment of rapid cycling bipolar disorder. Some investigators have reported success with carbamazepine in conjunction with other medications, while others have not. A psychopharmacologic algorithm for the treatment of rapid cycling bipolar disorder is proposed. There is a growing opinion among psychiatrists that patients who rapidly cycle should be treated with an anticonvulsant prior to lithium. However, until homogeneous cohorts of rapid cyclers undergo at least random assignment to different open treatments, these recommendations remain controversial. PMID- 7883738 TI - The relationship between substance abuse and bipolar disorder. AB - The significant prevalence of substance use disorders among patients with psychiatric illnesses has attracted increasing interest. One large epidemiologic study indicates that, of all Axis I disorders, bipolar disorder is the most likely to co-occur with alcohol or drug abuse. Evidence is emerging that shows that bipolar patients who also abuse drugs or alcohol have an earlier onset and worse course of illness compared with those who do not. They are more likely to experience irritable and dysphoric mood states, increased treatment resistance, and a greater need for hospitalization. Caution about diagnosing bipolar disorder in the presence of substance abuse is advised because of overlapping symptomatology. A rationale for the pharmacologic approach to treatment is explored. Data from several studies indicate that the presence of a substance use disorder may be a predictor of poor response to lithium. While it is possible that the anticonvulsants divalproex sodium and carbamazepine may be more useful in this population, a direct comparison of lithium with the anticonvulsants in a substance-abusing population of individuals with bipolar disorder has not yet been performed. Further investigation of diagnostic and treatment issues in this important population of patients with bipolar disorder is needed. PMID- 7883739 TI - Predictors of response to divalproex and lithium. AB - Predictors of response to mood stabilizers are of interest to psychiatrists because patients want and deserve prompt improvement, need to preserve limited hospital benefits, and desire agents that are both efficacious and free of adverse effects. Clinically practical guidelines for the likelihood of lithium responsiveness include mild and uncomplicated illness, pure manic symptomatology, prior response to lithium, and infrequent episodes. Divalproex has a broader spectrum of responders and has approximately equal benefit for patients with pure mania as for those with several forms of bipolar disorder that respond poorly to lithium (e.g., mixed mania, rapid cycling, comorbid substance abuse, and secondary bipolar disorder). Carbamazepine may be effective in patients who failed to respond to lithium and is more likely to be effective as part of combined drug therapy than as monotherapy. This review points out that, although the number of firm findings regarding predictors of response and the features associated with response are few, many of these can be combined with other general clinical information about the status of the patient to provide a guide to treatment selection and implementation of a therapeutic regimen. PMID- 7883740 TI - History of the development of valproate for treatment of bipolar disorder. PMID- 7883741 TI - Secondary mania: diagnosis and treatment. AB - Increasing evidence indicates that subtypes of bipolar disorder differ not only in symptomatology and associated clinical features, but by differences in age at onset, illness course, and response to treatment. Secondary manic states differ from typical bipolar states and are often especially difficult to treat. Although the correction of the underlying organic factors (toxic, metabolic, or infectious) may effectively reverse the manic presentation, many organic factors are not reversible (trauma, stroke, and aging), and the presence of these etiologic factors can complicate traditional antimanic treatments. Lithium may be effective for treating patients with secondary mania, but data from published studies show that in this population the associated adverse effects often limit its usefulness. Anticonvulsants appear to offer an effective alternative. Divalproex sodium, in particular, has been shown to be an effective and well tolerated treatment in open trials in the elderly and other patient groups with secondary mania. Controlled clinical trials are necessary to confirm the efficacy and tolerability of mood-stabilizing anticonvulsants in the treatment of secondary mania. PMID- 7883743 TI - Selective hydrolysis of tRNA by ethylenediamine bound to a DNA oligomer. AB - A sequence-selective artificial ribonuclease was prepared by attaching ethylenediamine to the 5'-end of a DNA oligomer as the sequence-recognizing moiety. The hybrid, incorporating a 19-mer DNA which is complementary with the A44-A62 sequence of tRNA(Phe), hydrolyzed the tRNA selectively at the 3'-side of C63. PMID- 7883742 TI - Mixed or dysphoric manic states: psychopathology and treatment. AB - Although the diagnostic criteria for the phenomenon of mixed states are not well defined, it is clear that this variant of bipolar disorder is prevalent, severe, and difficult to treat. The presence of complicating factors, such as substance abuse, neurologic insults or disorders, or developmental disorders, appears to increase the risk for developing mixed states. Several investigators have reported that patients with mixed episodes are less responsive to lithium therapy than are patients with pure mania. This review, however, reports that only limited data are available to support the efficacy of other antimanic agents. Divalproex appears to be more efficacious than lithium for patients in mixed states, but studies with larger patient populations are needed for confirmation. More than one agent may be required to bring about effective treatment, a factor that complicates simple comparator studies. When conventional pharmacotherapy fails, electroshock therapy often proves useful. PMID- 7883744 TI - Changes in ornithine metabolic enzymes induced by dietary protein in small intestine and liver: intestine-liver relationship in ornithine supply to liver. AB - Compared with the activity obtained with a high-protein diet in rats, a low protein diet doubled the activity of ornithine aminotransferase [EC 2.6.1.13] (OAT), a key enzyme for citrulline synthesis, in the small intestine. The induction of ornithine aminotransferase in the small intestine by the low-protein diet and its suppression by the high-protein diet, and the converse in the liver, were immunohistochemically verified with anti-OAT antiserum. The immunohistochemical studies revealed that ornithine aminotransferase molecules localized in the villous surface epithelia, but not in the cryptic epithelia, were most responsive to the changes in dietary conditions, these results indicating that intestinal ornithine aminotransferase may be involved in the ornithine supply to the liver, with the reversal of the enzyme reaction occurring with a low-protein diet. Reconstituted model experiments on citrulline synthesis revealed that the addition of ornithine carbamoyl-transferase and carbamoyl phosphate was essential to overcome the unfavorable equilibrium of the reverse reaction, and the further addition of glutamate dehydrogenase and ammonia resulted in a stimulating effect. PMID- 7883745 TI - Myosin subfragment-1 isoforms having different heavy chain structures from fast skeletal muscle of thermally acclimated carp. AB - Three heavy chain isoforms of chymotryptic myosin subfragment-1 (S1) with different molecular sizes of 96 kDa (H1), 94 kDa (H2), and 92 kDa (H3), were detected in the fast skeletal muscle from thermally acclimated carp. In total, six S1 isoforms were present, including two S1 isoforms for each heavy chain due to associated A1 and A2 light chains. H1 heavy chain was dominant in the 10 degrees C-acclimated carp and responsible for high acto-S1 Mg(2+)-ATPase activity and low thermostability. In contrast, H3 heavy chain predominating in the 30 degrees C-acclimated carp showed low acto-S1 Mg(2+)-ATPase activity and high thermostability. H2 heavy chain was found in the 10- and 20 degrees C-acclimated fish. H3 heavy chain featured three tryptic fragments with normal molecular masses of 25, 50, and 20 kDa in order from the N-terminus. However, H1 heavy chain contained an unusual, longer "20 kDa" peptide whose molecular size was estimated to be about 23 kDa. PMID- 7883746 TI - Computer prediction of general PCR products based on dynamical solution structures of DNA. AB - A computer program which can predict general PCR products was developed and experimentally verified to be useful. This means that the approximation of solution structures of DNA based solely on Watson-Crick base pairing is effective. Intramolecular higher structures were shown to be responsible for the discrepancies between the predictions and the experimental results. This study provides a theoretical background to arbitrarily primed (or random) PCR. Other basic issues relating to general PCR are also discussed. PMID- 7883747 TI - Induction of essential components of the superoxide generating system in human monoblastic leukemia U937 cells. AB - Cytochrome b558 composed of large and small subunits, and cytosolic 47- and 65 kDa proteins are important constituents of the superoxide (O2-) generating system in phagocytes and B lymphocytes. In this paper, we describe changes in O2(-) generating activity and expression of O2(-)-generating components during differentiation of human monoblastic leukemia U937 cells to macrophage-like cells. Undifferentiated U937 cells generated no O2- in response to a stimulation, although they expressed the three components other than the cytochrome b558 large subunit. When U937 cells were cultured with agents that induced the cell differentiation, such as vitamin D3, retinoic acid, interferon-gamma, and tumor necrosis factor, O2(-)-generating activity increased 5- to 200-fold depending on the agent used. Immunoblotting analysis revealed that the amounts of the four protein components essential for O2- generation increased, although their induction levels were significantly different between inducers. Among the four protein components, the cytochrome subunits were induced in low levels by all agents tested, which may explain why the O2(-)-generating activity of differentiated U937 cells was much lower than that of neutrophils from peripheral blood. PMID- 7883748 TI - Expression of mRNA for matrix gamma-carboxyglutamic acid protein during progression of atherosclerosis in aortae of Watanabe heritable hyperlipidemic rabbits. AB - In an effort to characterize mRNAs that are highly expressed during atherosclerosis, we employed differential hybridization screening of a cDNA library constructed from total RNA derived from the aorta of Watanabe heritable hyperlipidemic (WHHL) rabbits. Characterizing the cDNAs for mRNAs that are present in large amounts in WHHL rabbit aortae, we identified a positive clone encoding matrix gamma-carboxyglutamic acid protein (MGP). The primary structure of rabbit MGP was deduced from nucleotide sequence analysis of the cDNA. Northern blot analysis of total RNA prepared from aortae of WHHL and normal rabbits of various ages indicated that the expression of MGP mRNA increased in proportion to the progression of atherosclerosis in WHHL rabbits. Analysis of MGP mRNA by in situ hybridization revealed that a significant amount of MGP mRNA is accumulated in atherosclerotic lesions of WHHL rabbits, suggesting that the expression of MGP mRNA is correlated with the progression of atherosclerosis. PMID- 7883750 TI - Heat shock protein 90 strongly stimulates the binding of purified estrogen receptor to its responsive element. AB - We previously showed that the 9 S estrogen receptor (ER) could be reconstituted from purified ER and purified heat shock protein 90 (hsp 90). So, we investigated the role of hsp 90 in the binding of purified ER to an estrogen responsive element (ERE) by using the reconstitution system. ER purified from calf uterus showed a very low binding capacity to an ERE from the vitellogenin A2 gene in the gel mobility shift assay. However, the binding was strongly stimulated by reconstitution with hsp 90 and was proportional to the amount of reconstituted 9 S ER. Hsp 70, a typical molecular chaperone and a component of some steroid receptors, did not cause similar stimulation. The equilibrium dissociation constants (Kd) of the occupied and unoccupied 9 S ER for the ERE were the same as each other, indicating that the binding of ER to the ERE was independent of the ligand. H222, a monoclonal antibody which binds to the hormone-binding domain (HBD) of ER, recovered the high affinity ER-ERE binding. The binding of hsp 90 to ER suppressed the Triton X-100 stimulated estradiol-dissociation from the ER. The sedimentation coefficients and Stokes' radii of the purified and unpurified cytosolic ER were compared, and it was shown that the purified ER was not unfolded and had a rather compact structure, similar to the cytosolic ER.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883749 TI - Divalent metal ion-dependent mitochondrial degradation of unassembled subunits 2 and 3 of cytochrome c oxidase. AB - Intracellular protein degradation plays an important role in maintaining the stoichiometry of the different subunits of an oligomeric enzyme. In a Saccharomyces cerevisiae mutant defective in cytochrome c oxidase subunit 4 encoded in nuclear DNA, mitochondrial-encoded subunits 2 and 3 cannot assemble normally [Dowhan et al. (1985) EMBO J. 4, 179-184]. In this study, we show that those unassembled forms of subunits 2 and 3 in this strain are eliminated rapidly by degradation. Reduction of the intracellular ATP level by inhibiting the glycolytic pathway, or inhibition of the entry of ATP into mitochondria by bongkrekic acid, both of which are expected to reduce the intramitochondrial ATP level in respiratory-deficient cells such as WD1, significantly suppressed the degradation, suggesting that the degradation requires intramitochondrial ATP. The degradation was also inhibited by o-phenanthroline, a membrane-permeable metal chelator, and this inhibitory effect was suppressed by addition of an excess amount of Co2+, Mn2+, or Zn2+, but not by Ca2+ or Mg2+, suggesting a novel metal dependence of the degradation of unassembled Cox II and Cox III which has not been reported previously for mitochondrial metabolic protein degradation systems. A potential advantage of using this strain for identifying the factor(s) involved by a genetical approach is discussed. PMID- 7883751 TI - Hemolytic properties of Ca(2+)-treated human erythrocytes under hydrostatic pressure. AB - The effect of intracellular Ca2+ on high pressure-induced hemolysis of human erythrocytes was examined. Red cells were incubated with Ca2+ (0.01-1 mM) in the presence of ionophore A23187. The Ca(2+)-loaded cells were subjected to a pressure of 200 mPa. Treatment with 0.1 mM Ca2+ had the greatest suppressive effect on the hemolysis. On removal of intracellular Ca2+, red cells showed a morphological change from echinocytes to normal discocytes but the hemolysis remained unaltered. Measurement of intracellular K+ and viscosity demonstrated that the suppressive effect of Ca2+ on the hemolysis is irreversible and is largely associated with the increase of intracellular viscosity induced by K+ efflux. PMID- 7883752 TI - Identification of the reactive site of ascidian trypsin inhibitor. AB - A trypsin inhibitor from hemolymph of the solitary ascidian, Halocynthia roretzi, has been reported to be present in two forms, ATI-I and ATI-II. ATI-I consists of a single polypeptide chain with a unique sequence of 55 amino acid residues, while ATI-II has two chains that seem to be derived from ATI-I by cleavage at the Lys16-Met17 bond [Kumazaki, T., Hoshiba, N., Yokosawa, H., and Ishii, S. (1990) J. Biochem. 107, 409-413]. ATI-II (as modified inhibitor) was proved to be produced by incubation of ATI-I (as virgin inhibitor) with a catalytic amount of bovine trypsin. The tryptic hydrolysis at the Lys16-Met17 bond in virgin inhibitor showed a maximum velocity at around pH 3.5. On the other hand, acid treatment of a complex prepared by mixing equimolar quantities of trypsin and the the modified inhibitor yielded free trypsin and the virgin inhibitor. The results of chemical analyses indicated that the Lys16-Met17 bond that had been cleaved in ATI-II was resynthesized by the acid treatment. These findings strongly suggest that the Lys16-Met17 bond is the reactive site of ATI for trypsin. PMID- 7883753 TI - Activation of the alternative pathway of human complement by apoptotic human umbilical vein endothelial cells. AB - Complement activation generally does not occur on homologous cells. We observed C3 deposition on cultured human umbilical vein endothelial cells (HUVEC) when those which had died of apoptosis were treated with human serum. The C3 deposition on apoptotic HUVEC required Mg2+ but not Ca2+. In addition, the incubation of apoptotic HUVEC with purified C3, B, and D in the presence of Mg2+ resulted in C3 deposition. These results indicated that the C3 deposition on apoptotic HUVEC is mediated by the activation of the alternative complement pathway. C3 contains an intrachain thioester bond in the alpha chain (110 kDa) and upon activation to C3b, binds with membrane molecules by forming an ester or amide bond. Western blotting of reduced C3b-membrane molecule complexes, isolated from serum-treated apoptotic HUVEC by immunoprecipitation with anti-C3, revealed the covalent binding of C3b to several membrane molecules. Most of the C3b membrane molecule complexes were cleaved by hydroxylamine, suggesting covalent binding via an ester bond. The molecular mass of the major alpha chain fragment released by hydroxylamine treatment was not 105 kDa but 68 kDa, which corresponds to the alpha 1 fragment of iC3b. These results indicate that most of the C3b on HUVEC was cleaved at its alpha' chain to yield iC3b, which consists of three disulfide-linked polypeptide chains and is a ligand of the complement receptor type 3 (CR3) of phagocytes. These results suggest that apoptotic HUVEC can activate the alternative pathway of the homologous complement and that the complement is related to the clearance of apoptotic cells by phagocytes. PMID- 7883754 TI - Characterization of hamster CYP1A1 gene: inducible expression and negative regulation. AB - A genomic clone encoding the hamster CYP1A1 gene was isolated from a hamster EMBL 3 genomic library and characterized. The CYP1A1 gene contained seven exons including the noncoding first exon as determined for CYP1A1 of other species. DNA sequence analysis up to -2307 bp of the CYP1A1 gene revealed the occurrence of five consensus xenobiotic responsive elements (XREs) and one basal transcription element (BTE) in addition to the canonical TATA box. For functional analysis, transfection experiments were performed in human hepatoma HepG2 cells with reporter gene constructs consisting of fragments with various lengths of the 5' flanking region of the CYP1A1 gene and bacterial chloramphenicol acetyltransferase (CAT) gene. External deletion of the upstream region from the reporter gene resulted in a stepwise decrease of the CAT activity, suggesting that XREs were responsible for inducible expression of CYP1A1 gene by 3 methylcholanthrene (MC). A negative regulatory element (NRE) was also identified in the 5'-flanking region at -833 to -642. Removal of the NRE from the CYP1A1-CAT fusion gene resulted in about 3-fold increase of MC-inducible CAT activity. Using gel retardation assays with HepG2 nuclear extract, we demonstrated the presence of a specific protein which bound to the NRE fragment. Further competition analysis and methylation interference assays revealed that the nuclear protein bound to a 22-base fragment (from -688 to -709) of the NRE region, whose sequences were conserved among hamster, human, and rat CYP1A1 genes. PMID- 7883756 TI - Isolation and characterization of the prolyl aminopeptidase gene (pap) from Aeromonas sobria: comparison with the Bacillus coagulans enzyme. AB - The Aeromonas sobria pap gene encoding prolyl aminopeptidase (PAP) was cloned. It consists of 425 codons and encodes a homotetrameric enzyme of 205 kDa. The purified enzyme showed an almost absolute specificity for amino-terminal proline. Proline and hydroxyproline residues from many peptide and amide substrates could be easily removed, while no activity was detected for substrates having other amino terminals. The enzyme was very similar to that from Bacillus coagulans in many aspects, such as the strong inhibition caused by PCMB and the weak or no inhibition caused by DFP and chelators, respectively. However, these enzymes show only 15% identity in their amino acid sequences. Differences were also observed in their molecular weight, stability and activity toward some peptide substrates. When aligning the deduced amino acid sequence with known sequences from other microorganisms, conserved sequences were found at the amino-terminal region; the significance of these conserved regions is discussed. Based on the results of this work, and on the studies available to date, the occurrence of at least two types of PAPs is postulated. One group would be formed by the Bacillus, Neisseria, and Lactobacillus enzymes, and the other by enzymes such as the Aeromonas PAP. PMID- 7883755 TI - Structural analysis of underivatized and derivatized aminophospholipids and phosphatidic acid by positive ion liquid secondary ion and collisionally induced dissociation tandem mass spectrometry. AB - This paper describes an approach for structurally analyzing aminophospholipids, including glycerophosphatidylethanolamine, glycerophosphatidylserine and their lyso analogues, and glycerophosphatidic acid by positive-ion liquid secondary-ion and four-sector tandem mass spectrometry. Polar head groups and the composition and position of the fatty acid chains in aminophospholipid species as well as diacyl and monoacyl phosphatidylethanolamine and their plasmalogen species can be characterized by collisionally induced dissociation of [M+H]+ ions of underivatized molecular species. Tandem mass spectrometry of [M+Na]+ and [M + 2Na H]+ ions of 9-fluorenylmethyloxycarbonyl-derivatized glycerophosphatidylethanolamine and glycerophosphatidylserine induces fragmentation processes, but product ions are generally less structurally informative. Collisionally induced dissociation of [M + 2Na-H]+ ions of the molecular species of glycerophosphatidic acid not only yields information on the composition and position of fatty acid chains, but also allows the double bond location to be identified. This common positive-ion method is particularly effective in characterizing the molecular species of natural ethanolamine glycerophospholipids because of the advantage of a low detection limit. This approach also represents a useful alternative for the analysis of the molecular species from natural aminophospholipids by tandem mass spectrometry. PMID- 7883757 TI - Role of transit peptide sequence of plastocyanin for its expression, processing, and copper-binding activity in Escherichia coli. AB - Plastocyanin is a copper protein that functions as an electron carrier in the thylakoid lumen of the chloroplast. To characterize the transit peptide of plastocyanin and develop expression systems for it in Escherichia coli, three kinds of expression vectors which encode different size precursor plastocyanin molecules were constructed. Their expression, processing, and copper-binding activity have been examined. When the full-length cDNA encoding the precursor plastocyanin from Silene pratensis was expressed in E. coli, a large amount of precursor plastocyanin accumulated in insoluble aggregates. Its accumulation level was increased by the addition of copper ions. About six percent of precursor plastocyanin molecules were transported into the periplasmic space and processed to the mature protein. On the other hand, expression of the intermediate size cDNA, which contains the hydrophobic domain and basic amino acid of C-terminal transit peptide, caused exclusive translocation to the periplasmic space and correct processing to the mature size. The addition of copper ions increased the holo-protein content, but did not change the polypeptide content of mature plastocyanin, indicating that translocation and processing are independent of the incorporation of copper ions. The mature plastocyanin content corresponds to 8% (w/w) of the total E. coli protein content (123 mg per liter of culture). The purified mature holo-protein showed almost the same spectroscopic and kinetic properties as those of purified spinach plastocyanin. Expression of the cDNA encoding the mature polypeptide and two preceeding amino acid residues caused the accumulation of only a small amount of plastocyanin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883758 TI - Possible involvement of lipoxygenase metabolites of arachidonic acid in the regulation of pregnenolone synthesis in bovine adrenocortical mitochondria. AB - Our previous investigations demonstrated that 5- and 15-lipoxygenase metabolites of arachidonic acid are synthesized in bovine adrenal fasciculata cells, although their exact role in the regulation of adrenal steroidogenesis is unknown. Thus we attempted to investigate their direct effects on cholesterol side-chain cleavage in bovine adrenal mitochondria. We also examined Ca2+ efflux in mitochondria, based on a reported correlation between pregnenolone formation and Ca2+ release in adrenal mitochondria. The present experiments showed that 5-HETE increased pregnenolone generation in the isolated intact mitochondria, but not in the inner mitochondrial membrane. Thus it is suggested that 5-HETE may activate cholesterol side-chain cleavage by inducing the translocation of cholesterol from the outer to the inner mitochondrial membrane. The present experiments also demonstrated that 5-HPETE, 5-HETE, 15-HPETE, and 15-HETE, but not leukotriene B4, activated cholesterol side-chain cleavage and Ca2+ efflux from mitochondria, suggesting that these substances may activate cholesterol side-chain cleavage by regulating Ca2+ movement in mitochondria. These effects were additively enhanced when mitochondria were stimulated simultaneously with these substances and GTP. Therefore, both GTP and lipoxygenase metabolites seem to play crucial roles in the regulation of pregnenolone generation. The direct effect of 5- and 15 lipoxygenase metabolites other than leukotriene B4 on the regulation of pregnenolone synthesis, which is known to be the rate-limiting step of steroidogenesis, were clearly observed in the present experiments. PMID- 7883759 TI - Site- and strand-specific nicking at oriT of plasmid R100 in a purified system: enhancement of the nicking activity of TraI (helicase I) with TraY and IHF. AB - We developed a purified system for reproducing the nicking reaction at the site 59 base pairs upstream of the TraY protein binding site, sbyA, in the oriT region of plasmid R100. Nicking at oriT occurred efficiently in the presence of the plasmid-encoded proteins, TraI and TraY, integration host factor (IHF), and Mg2+, but inefficiently in the presence of the TraI protein and Mg2+. The products were complex DNA molecules with a protein covalently linked with the 5' end of the nick in the strand, which is supposed to be transferred during conjugation. The same complex DNA molecules were formed in the presence of the TraI protein alone, indicating that the protein attached at the 5' end of the nick is the TraI protein. Stimulation of the nicking reaction by the TraY protein and by IHF, whose binding site has been mapped between the nicking site and sbyA, indicates that DNA bending is important in the formation of the complex including the TraI and TraY proteins at oriT. PMID- 7883760 TI - Human arylhydrocarbon receptor: functional expression and chromosomal assignment to 7p21. AB - We isolated the human arylhydrocarbon receptor (AhR) cDNA from a human lung cDNA library, by using mouse AhR cDNA as a labeled probe. The nucleotide sequence of cloned human AhR cDNA is identical to the previously reported human AhR sequence [Dolwick et al. (1993), Mol. Pharmacol. 44, 911-917] from cell line HepG2. The overall amino acid identity with mouse AhR from cell line Hepa-1 is 72.5%. The human AhR expressed either in COS-7 cells or in a reticulocyte lysate in vitro translation system showed specific dioxin-binding activity and Arnt-dependent DNA binding activity. Chromosomal localization of the AhR gene was determined to be chromosome 7p21 by fluorescent in situ hybridization and DNA blot hybridization using 23 human x mouse or Chinese hamster hybrid cell DNAs. PMID- 7883761 TI - An S-alkylating reagent with positive charges as an efficient solubilizer of denatured disulfide-containing proteins. AB - A novel S-alkylating reagent, N-(3-bromopropyl)-N,N,N',N',N'-pentamethyl-1,3 propanedi(ammonium bromide) (TAP2-Br) which carries two positive charges in the molecule, was prepared to increase the solubility or to decrease the hydrophobicity of cysteine-containing denatured proteins (or peptides). S Alkylation with TAP2-Br introduces two positive charges per cysteine residue, which will effectively shift the net charge of a protein in the positive direction. Disulfide-containing proteins, such as hen egg-white lysozyme, RNase A, BSA, and soybean trypsin inhibitor (Kunitz type), were reduced and S-alkylated with TAP2-Br to evaluate the potential of this reagent compared with other S alkylating reagents such as monoiodoacetic acid, bromosuccinic acid and (3 bromopropyl)trimethylammonium bromide. The solubilities of these denatured proteins in the pH range of 2-10 indicated that S-alkylation with TAP2-Br effectively solubilized not only basic proteins (lysozyme and RNase) but also an acidic protein containing a fairly large number of cysteine residues (BSA). Moreover, the retentions of cysteine-containing tryptic peptides derived from lysozyme on reversed-phase HPLC were greatly reduced by S-alkylation with TAP2 Br. These results indicate that TAP2-Br is very useful to increase the solubility of some cysteine-containing denatured proteins and to decrease the hydrophobicity of peptides containing cysteine residue(s). PMID- 7883762 TI - Intracellular calcium dependent activation of p72syk in platelets. AB - We previously demonstrated that thrombin-induced activation of p72syk was independent of intracellular Ca2+ elevation in platelets. However, our previous studies also demonstrated that activation of platelets by ionophore A23187 results in a dramatic increase in tyrosine phosphorylation of several cellular proteins. In the present study, we investigated the effect of Ca2+ elevation on the activity of p72syk. When washed porcine platelets were stimulated with ionophore A23187 and the activity of p72syk was assessed by means of an immunoprecipitation kinase assay, A23187 caused a time- and dose-dependent increase in the specific activity of p72syk. In addition, pretreatment of platelets with both aspirin and ADP scavengers or chelation of extracellular Ca2+ by EGTA had no effect on the A23187-induced activation of p72syk. These results indicate that A23187-induced activation of p72syk is independent of the formation of endoperoxide/thromboxane A2, released ADP and extracellular Ca2+, suggesting the existence of a novel pathway for activation of p72syk. Furthermore, evidence is presented which indicates a synergistic effect of A23187 and thrombin on the activation of p72syk, and an inhibitory effect of pretreatment with phorbol 12 myristate 13-acetate, a protein kinase C activator, on the activation of p72syk induced by either A23187 or thrombin. PMID- 7883763 TI - Role of Ca2+ in the binding of phospholipase A2 with a monomeric substrate and with its amide-type analog. AB - Effects of Ca2+ on the kinetic parameters for the hydrolysis of monodispersed 1,2 dihexanoyl-sn-glycero-3-phosphorylcholine (diC6PC), catalyzed by Group I phospholipases A2 (PLA2s) from Pseudechis australis, Naja naja atra, and bovine pancreas and by Group II enzymes from Vipera russelli russelli, Agkistrodon halys blomhoffii, and Trimeresurus flavoviridis, were studied by the pH-stat assay method at 25 degrees C, pH 7.5-8.2, and an ionic strength of 0.1 or 0.2 in the absence or presence of an amide-type substrate analog, 2-dodecanoyl-amino-1 hexanol-phosphoglycol. The binding of genuine substrate to the Group II enzymes and that of its analog to the Groups I and II enzymes were markedly facilitated by the binding of Ca2+ to the enzymes. On the other hand, the binding of genuine substrate to the Group I enzymes was found to be independent of the Ca2+ binding. The former result suggests that the structures of the Group II enzyme-genuine substrate complexes and both types of enzyme-analog complexes are generally stabilized by the Ca2+ binding, whereas the latter indicates that the structures of the Group I enzyme-genuine substrate complexes are already similar to those of their Ca2+ complexes and that, therefore, these enzyme-substrate interactions are independent of the Ca2+ binding. PMID- 7883764 TI - Human centromere protein C (CENP-C) is a DNA-binding protein which possesses a novel DNA-binding motif. AB - Mammalian centromere proteins (CENPs) can be divided into those that translocate from centromere to midzone in the progress of mitosis, and those that remain at the centromere throughout the cell cycle. The latter including CENP-A, CENP-B, and CENP-C is the candidate for DNA-binding protein. CENP-B has been shown previously to possess the specific DNA-binding activity to 17-base pair sequences dispersed on human centromeric alphoid repeats. In this study, we examined DNA binding property of CENP-C that is localized to inner kinetochore plate of the metaphase chromosome. We independently isolated a full-length cDNA encoding human CENP-C and expressed it as the polypeptide tagged with histidine oligomer in Escherichia coli. After affinity purification with Ni(2+)-chelated resin, DNA binding activity of the recombinant CENP-C renatured on the membrane was demonstrated by using human genomic DNA and an alphoid subfamily in South-Western type blotting analysis. By constructing a series of truncated products, the DNA binding domain was located at an internal 101-amino-acid stretch with no apparent homology to any other DNA-binding proteins. This may suggest that CENP-C is directly involved in formation of kinetochore chromatin fibers. PMID- 7883765 TI - Activation of phospholipase D in Chinese hamster ovary cells expressing platelet activating factor receptor. AB - Platelet-activating factor (PAF) activated phospholipase D (PLD) in WT-H cells, CHO cells stably expressing cloned guinea-pig PAF receptor. The PLD activation was found to be dependent on extracellular Ca2+, protein kinase C (PKC), and a currently unidentified protein tyrosine kinase (PTK). PTK inhibitors ST-638 and genistein inhibited PLD activation induced by PAF as well as phorbol myristate acetate, indicating that PTK acts downstream of PKC. Furthermore, activation of MAP (mitogen-activated protein) kinases, as assessed by their phosphorylation, was also dependent on Ca2+, PKC, and PTK. The correlation between PLD activity and MAP kinase activation, together with the previously observed MAP kinase activation associated with arachidonic acid release by cPLA2 [Honda et al. (1994) J. Biol. Chem. 269, 2307-2315], led us to examine the involvement of MAP kinase in PLD activation. The results indicate that PLD and MAP kinases are activated through the common pathway consisting of Ca2+, PKC, and the unidentified PTK, which act in parallel, but not in a linear sequence. PMID- 7883766 TI - Targeting of the immunoglobulin-binding domain of protein A to the extracellular matrix using a minifibronectin expression vector. AB - A truncated form of fibronectin consisting of the N-terminal 70-kDa and C terminal 37-kDa regions, referred to as "minifibronectin," retains the ability to assemble into the extracellular matrix, even though it lacks the central approximately 120-kDa region containing most of the type III modules (Ichihara Tanaka, K., Titani, K., and Sekiguchi, K., FEBS Lett. 299, 155-158, 1992). Taking advantage of the matrix assembly activity of minifibronectin, we developed a novel method to target non-matrix proteins to the extracellular matrix by inserting them between the N-terminal 70-kDa and the C-terminal 37-kDa regions of minifibronectin. Using the immunoglobulin-binding domain of Staphylococcal protein A as a model, we demonstrated that the bacterial protein expressed in mouse L cells as a chimeric protein with minifibronectin is secreted as disulfide bonded dimers and successfully deposited onto the extracellular matrix of transfected cells. The chimeric protein retained the immunoglobulin-binding activity not only in solution but also after deposition at the matrix. This targeting strategy we developed will provide a means to manipulate the biological functions of the extracellular matrix through targeting of a wide variety of non matrix proteins. PMID- 7883767 TI - Classification of signals for blocking apoptosis in vascular endothelial cells. AB - The survival and death of human umbilical vascular endothelial cells in culture are affected by several factors, such as fibroblast growth factor (FGF), serum, phorbol ester (TPA), and vanadate. In order to identify common aspects of the various signal-transduction processes during the course of apoptotic or programmed cell death, we designed experiments to distinguish between these factors in terms of the pathway that is responsible for the processing of each stimulus. We found, for example, that the effect of removal of FGF was specifically overcome by the addition of the phorbol ester. Our results indicated that two distinct pathways were operative, one specific for signal transduction initiated by FGF and phorbol ester and another specific for signal transduction initiated by serum and vanadate. These two pathways merged down-stream of the individual signal-processing pathways. PMID- 7883768 TI - Perchlorate-induced formation of the alpha-helical structure of mastoparan. AB - Mastoparan, a basic tetradecapeptide from wasp venom, has been considered to be unfolded under aqueous conditions. On the basis of the far-UV circular dichroism spectrum, we found that sodium perchlorate at molar concentrations stabilizes an alpha-helical structure of mastoparan. To understand the mechanism of the perchlorate-induced stabilization of the alpha-helical structure, we synthesized a dimeric form of mastoparan derivative, which was linked at the C terminal by a disulfide bond. The linkage decreased the concentration of perchlorate required to stabilize the alpha-helical structure by 30-fold. With the dimeric mastoparan derivative, we measured the effects of several salts such as sodium trichloroacetate, sodium trifluoroacetate, and sodium chloride. The concentration of salts required to induce the conformational transition varied and the order of effectiveness of different salts was consistent with the electroselectivity series of anions toward anion-exchange resins, indicating that the anion binding to the positively charged amino groups is responsible for the transition. These results suggest that the salt-induced formation of the alpha-helical state of mastoparan can be explained by a mechanism similar to that proposed for the salt induced conformational transition of melittin. PMID- 7883769 TI - Identification and characterization of the ackA (acetate kinase A)-pta (phosphotransacetylase) operon and complementation analysis of acetate utilization by an ackA-pta deletion mutant of Escherichia coli. AB - The pta gene encoding phosphotransacetylase was cloned on a high copy plasmid with or without the ackA gene encoding acetate kinase in Escherichia coli. The acetate kinase and phosphotransacetylase were overproduced in cells harboring the plasmid possessing both genes. Nucleotide sequencing of the pta gene revealed that it is able to produce a polypeptide comprising 714 amino acid residues, which starts at 70 base pairs downstream from the stop codon of the ackA gene. The 77-kDa protein band of overproduced phosphotransacetylase was observed on SDS polyacrylamide gel electrophoresis, of which the amino terminal sequence corresponds to that of the deduced polypeptide without the amino terminal methionine. Two transcripts of pta of different sizes were found in the cells. A 3,700 nucleotide transcript, which covers the ackA and pta genes, seemed to be produced by the first promoter in the operon and a 2,300 nucleotide transcript, which covers just pta, seemed to be produced by the second promoter. In a synthetic medium containing acetate as the sole carbon source, the growth of an ackA-pta double mutant was greatly impaired. Complementation analyses revealed that both the acetate kinase and phosphotransacetylase were required for the rapid growth in the acetate medium. PMID- 7883770 TI - Purification and characterization of Ca2+/calmodulin-dependent protein kinase IV kinase from rat brain. AB - Calmodulin-dependent protein kinase IV (CaM-kinase IV) kinase was recently discovered in the rat brain by its activity to activate the inactive recombinant CaM-kinase IV expressed in Escherichia coli [Okuno, S. and Fujisawa, H. (1993) J. Biochem. 114, 167-170]. In the present study, CaM-kinase IV kinase was purified approximately 2,000-fold from rat cerebral cortex by purification procedures including calmodulin affinity chromatography, and its properties were examined. The highly purified CaM-kinase IV kinase gave one major protein band corresponding to a molecular weight of about 66,000 upon SDS-PAGE. The purified CaM-kinase IV kinase phosphorylated and concomitantly activated CaM-kinase IV purified from rat brain as well as the recombinant kinase expressed in Escherichia coli in a Ca2+/calmodulin-dependent manner. The phosphorylation of CaM-kinase IV by CaM-kinase IV kinase occurred on only serine residue(s). Among a number of proteins, including several known to be phosphorylated by the various protein kinases tested, CaM-kinase IV was the best substrate for CaM-kinase IV kinase. Since syntide-2, a synthetic peptide known to be a good peptide substrate for calmodulin-dependent protein kinase II (CaM-kinase II), was a fairly good substrate for CaM-kinase IV kinase, some kinetic properties of CaM-kinase IV kinase were examined using syntide-2 as a substrate. The Km value for the peptide substrate in the presence of Ca2+/calmodulin was almost two orders of magnitude lower than that in its absence, although the Vmax value was almost the same in the presence and absence of Ca2+/calmodulin. PMID- 7883771 TI - Construction and characterization of chimeric enzyme consisting of an amino terminal domain of phenylalanine dehydrogenase and a carboxy-terminal domain of leucine dehydrogenase. AB - Phenylalanine dehydrogenase of Thermoactinomyces intermedius acts preferentially on L-phenylalanine and L-tyrosine, whereas leucine dehydrogenase of Bacillus stearothermophilus acts almost exclusively on L-leucine and some other branched chain L-amino acids. The two enzymes share a sequence similarity (47%). Aiming at elucidation of the mechanism of substrate recognition by the two amino acid dehydrogenases, we have genetically constructed a chimeric enzyme consisting of an N-terminal domain of phenylalanine dehydrogenase containing the substrate binding region and a C-terminal domain of leucine dehydrogenase containing the NAD(+)-binding region. The chimeric enzyme purified to homogeneity acted on phenylalanine with a specific activity of 6% of that of the parental phenylalanine dehydrogenase and showed a broad substrate specificity in the oxidative deamination, like phenylalanine dehydrogenase. However, it acted much more effectively than phenylalanine dehydrogenase on isoleucine and valine. Its Km values for L-phenylalanine and L-leucine were similar to those of phenylalanine dehydrogenase. The substrate specificity of the chimeric enzyme in the reductive amination was an admixture of those of the two parent enzymes. These results suggest that the two domains of phenylalanine dehydrogenase and leucine dehydrogenase probably can fold independently. Accordingly, their chimera forms a new active enzyme which consists of their N- and C-terminal domains containing the substrate- and coenzyme-binding regions, respectively. However, the two domains of chimeric enzyme interact and communicate with each other to form a new active site and consistently show the new substrate specificity. PMID- 7883772 TI - Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial. AB - A phase II trial of menadione (2.5 g/m2 as a continuous intravenous infusion over 48 h) followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4-6 weeks was performed in 43 patients with advanced gastrointestinal cancer. Menadione, a vitamin K analog that lowers intracellular pools of reduced glutathione, was combined with mitomycin C in an attempt to overcome thiol mediated resistance to alkylating-agent chemotherapy. The median age of patients entered on this trial was 58 years; performance status ranged from 60%-100%. None of the 43 evaluable patients obtained an objective response to this combination regimen. Median survival was 6.6 months. Treatment with menadione and mitomycin C was reasonably well tolerated except for hematological toxicity. A total of 27% of treatment courses were complicated by grade 3 or 4 hematological toxicity including one episode of hemolytic anemia and one episode of hemolytic uremic syndrome. One patient developed irreversible interstitial pneumonitis, and 1 patient had an asymptomatic decrease in the left-ventricular ejection fraction. Despite preclinical evidence indicating that menadione pretreatment enhances the cytotoxicity of mitomycin C, our study documents the resistance of advanced gastrointestinal cancers, particularly colorectal cancer, to mitomycin C modulated by menadione. PMID- 7883773 TI - Prognostic value of proliferating cell nuclear antigen and c-erbB-2 compared with conventional histopathological factors in breast cancer. AB - Expression of proliferating cell nuclear antigen (PCNA) and c-erbB-2 oncoprotein has been assessed in 471 women with breast cancer to evaluate their prognostic value as compared to conventional histopathological factors. In univariate analysis, high PCNA expression (> or = 20%) predicted a significantly worse survival in lymph-node-negative tumors (univariate P = 0.031). However, the effect disappeared in multivariate analysis and the histological grade remained the only independent factor for this group. Despite its close correlation to histological grade (P < 0.001), PCNA expression discriminated subsets with different survival within the heterogeneous group of moderately differentiated tumors (univariate P = 0.073, multivariate P = 0.075). PCNA expression was not found to be a significant prognostic factor in lymph-node-positive tumors, thus it was of limited value for breast cancer patients as a whole. c-erbB-2 protein overexpression was associated with a worse survival (univariate P = 0.019, multivariate P = 0.057) for the entire group of patients. The effect was mainly attributed to the significance of c-erbB-2 as an independent factor in lymph-node positive (up to three nodes, multivariate P = 0.04; four or more nodes: multivariate P = 0.017) and large tumors (> 2 cm: multivariate P = 0.002). c-erbB 2 was without significance in lymph-node-negative patients. Though both factors might amplify the prognostic information for distinct patient subsets they do not achieve the strong prognostic value of conventional histopathological features in breast cancer. PMID- 7883774 TI - Nomograms for determining the probability of axillary node involvement in women with breast cancer. AB - We have previously reported that a history of pregnancy is independently associated with axillary node involvement in breast cancer patients. We have now studied additional women with breast cancer and have used our data and the logistic model to produce nomograms for determining the risk of axillary node involvement, based on tumor size, age, and number of pregnancies. There was an increase in the incidence of axillary node involvement in women with a history of pregnancy. To exclude the confounding effect that tumor size or age might have on node involvement, logistic regression was performed. Pregnancy, tumor size, and age were the three independent variables. History of pregnancy had a significant effect on node involvement (P = 0.036) that was independent of tumor size and age. Nomograms were constructed from these data. Surgeons do not perform an axillary dissection in every breast cancer patient. If the axilla is clinically negative and the tumor small, the surgeon, medical oncologist, and radiation oncologist may decide that a dissection need not be done. The nomograms in this article may allow for a more methodical choice of patients for axillary dissection. Moreover, a radiation oncologist might use the nomograms to help decide whether to irradiate an undissected axilla. PMID- 7883775 TI - Possible lack of full cross-resistance of 5HT3 antagonists; a pilot study. AB - We investigated the potential of cross-over to the serotonin receptor (5HT3) antagonist ondansetron after protection failure with tropisetron. Several cases of complete protection were observed. These limited data suggest that there is an indication for retreatment with a different 5HT3 antagonist after an initial failure to another and also stress the need and relevance for comparative studies between 5HT3 antagonists. PMID- 7883776 TI - A prospective randomized evaluation of three schedules of mesna administration in patients receiving an ifosfamide-containing chemotherapy regimen: sustained efficiency and simplified administration. AB - Chemotherapy with oxazaphosphorines, such as ifosfamide, is often limited by unacceptable urotoxicity. Without uroprotection hemorrhagic cystitis becomes dose limiting. Mesna, a thiol compound, is a drug able to bind the toxic metabolites, forming nontoxic compounds in the urine. A total of 122 patients were enrolled in this study and 228 chemotherapy cycles with an ifosfamide-containing regimen were performed (225 evaluable). Mesna was given at the same total dose as the ifosfamide in all arms. On arm A, mesna was given i. v. in equal doses 15 min before and 4 h and 8 h following the ifosfamide dose. On arm B, mesna was given in three equivalent doses 15 min before (i.v.) and 4 h (i.v.) and 8 h (p.o., double dose) following ifosfamide. On arm C, mesna was given i.v. in two equal doses given 15 min before and 4 h following. The incidence of urotoxicity was very low (lower than 15%) in the three arms, 0% in A, 1.36% in B and 2.70% in C. All three arms were equally efficient. Schedule C was considered superior to the others, since it was equally effective, simpler and more convenient. PMID- 7883777 TI - Influence of hexadecylphosphocholine on the release of tumor necrosis factor and nitroxide from peritoneal macrophages in vitro. AB - Hexadecylphosphocholine (HPC) has been investigated intensively for its cancerostatic properties. One explanation for the mechanism of action of HPC assumes that it plays a role in stimulation of the immune system. In particular, its potency to activate macrophages has already been recognised for different lyso- and ether lipids. Important steps in the cascade for developing cytotoxic effects of macrophages on tumor cells are the release of nitric oxide radicals (NO) and/or tumor necrosis factor (TNF). The aim of our study was to examine the role of HPC as primer and/or trigger for macrophage activation to cytotoxicity. In our experiments we used HPC in free (micellar) or liposomal form in different primer/trigger combinations with lipopolysaccharide (LPS). A weak change in morphology was revealed by electron microscopy, if macrophages were harvested from mice previously treated with HPC or HPC multilamellar vesicles. This observation was quantified by the measurement of NO, TNF and cytotoxic activity of the peritoneal macrophages. A specific release of NO was induced by the combination of in vivo treatment with liposomal HPC and subsequent stimulation by LPS in vitro. This process started only after 12 h of in vitro incubation of macrophages with the endotoxin. The release of TNF was dependent of the primer/trigger combination used. A moderate priming effect was obtained with HPC in liposomal form independently of the trigger. On the other hand, liposomes as priming agents were found to induce a dramatic increase in TNF release after in vitro coculture with the trigger LPS. The high release of NO and TNF is accompanied by only a weak increase in tumor cytostasis. The best results were once more found with macrophages primed with liposomal HPC and then triggered with LPS. PMID- 7883778 TI - Growth stimulation of ferritin of human leukemia cells in vitro. AB - Ferritin has been reported to inhibit the growth of some leukemia cells in serum supplemented culture. Recently we have found that ferritin stimulates the proliferation of human acute myeloblastic leukemia cells HL-60 and erythroleukemia cells K-562-T1 in serum-free medium. In this study, we examined the effect of ferritin against 14 human leukemia cell lines using human heart ferritin in serum-depleted culture medium. Among 14 cell lines tested, 10 were stimulated to proliferate by ferritin (maximum response at 30-300 ng/ml) with 0 1% fetal calf serum (FCS). The growth of all the cell lines was significantly inhibited by ferritin in the presence of 10% FCS. These results suggest that ferritin has dual functions; it promotes the growth of leukemia cells with low concentrations of FCS, but suppresses their growth with high concentrations of FCS. PMID- 7883779 TI - TP53 gene mutations in gastric carcinoma detected by polymerase chain reaction/single-strand conformation polymorphism analysis of archival material. AB - TP53 gene mutations, one of the most common alterations described in human tumors, have also been detected in gastric carcinoma, and shown to occur rather late in disease progression. A better assessment of the prognostic value of TP53 gene mutations can be obtained by examining archival material, as this allows stored cases with well-defined histories to be monitored. We performed immunohistochemical and polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analyses of formalin-fixed paraffin-embedded material from nine selected cases of gastric carcinoma at different pathological stages. PCR-SSCP analysis of TP53 exons 5-8 detected missense point mutations in two out of five immunostain(PAb1801)-positive tumors, and a deletion (allowing for a premature stop codon) in one of the remaining four immunostain-negative tumors. Thus, PCR-SSCP analysis represents a feasible strategy for the detection of TP53 alterations in archival material of gastric carcinoma cases. PMID- 7883780 TI - Synergistic interactions between interferon beta and carboplatin on SK-MEL 28 human melanoma cell growth inhibition in vitro. AB - Carboplatin and interferon beta (IFN beta) were tested alone and in combination for their antiproliferative activity on the human melanoma cell line SK-MEL 28 in vitro. Cells were incubated for 4 days in the presence of carboplatin (0.1 mM and 0.1 microM) and interferon beta (5 pM and 5 nM) and cell growth inhibition was determined by the sulphorhodamin B assay. The antiproliferative effects of the drug combinations were analysed using Berenbaum's hyperplane theorem to determine additive, synergistic and antagonistic effects. IFN beta was found to be 10,000 times more active in inhibiting cell growth of SK-MEL 28 cells than carboplatin on the basis of IC50 values (IFN beta: IC50 = 1.24 nM, carboplatin: IC50 = 18.2 microM). The addition of IFN beta at 0.5 nM reduced the IC50 value of carboplatin 18.0-fold; with IFN beta at 0.05 nM a dose reduction of 1.84 was measured. At the carboplatin: IFN beta molar concentration ratios of 2000:1 and 6000:1, interaction indices (I) of 0.66 and 0.83 were determined respectively, indicating synergistic interactions between the two drugs. At higher carboplatin: IFN beta molar ratios (20,000:1 and 60,000:1) an additive interaction was observed (I = 1.07 and 1.20). However, further in vitro studies with several melanoma cell lines are necessary to evaluate the potential effectiveness of the drug combination of carboplatin and IFN beta for eventual clinical utilisation. PMID- 7883781 TI - Characterization of chemotherapy-induced morphonuclear modifications in the P388 leukaemia and the MXT mammary tumour models of the mouse. AB - Chemotherapy-induced morphonuclear modifications were monitored in vivo by means of the digital cell image analysis of Feulgen-stained nuclei. Two experimental models were used, i.e. the P388 mouse leukaemia and the MXT mouse mammary carcinoma. The drugs used were doxorubicin, etoposide and cyclophosphamide. The results indicate that the chemotherapy induced a significant decrease in the MXT tumour growth and a significant increase in the survival of the P388 leukaemic mice. These effects were accompanied at the morphonuclear level by an increase in the nuclear area, by modifications in the DNA content in accordance with the effects of the drugs on the cell cycle and by several modifications in the chromatin texture in accordance with the model or the drugs studied. While there were neither homogeneous morphonuclear changes in all treatment groups nor clearcut correlations between the morphonuclear changes and tumour growth or the survival of the animals, the present study nevertheless shows that it is possible, at least partly, to monitor in vivo certain chemotherapy-induced effects occurring at the morphonuclear level, and subsequently to obtain information on the mode of action of the drugs. PMID- 7883782 TI - 6-Amino-6-deoxyascorbic acid induces apoptosis in human tumor cells. AB - 6-Amino-6-deoxyascorbic acid was found to inhibit human tumor cell growth. The antitumor effect depends on the tumor type and concentration of the acid. After cell treatment with 6-amino-6-deoxyascorbic acid, drastic morphological changes were found. Although image analysis did not show a difference in p53 and c-myc gene expression, the appearance of chromatin aggregation and DNA fragmentation points to apoptosis or programmed cell death. PMID- 7883783 TI - Wilms' tumour--a case of disrupted development. AB - Wilms' tumour is a paediatric kidney malignancy that arises through aberrant differentiation of nephric stem cells. We are studying the role of one Wilms' tumour predisposition gene, WT1. This is a tumour suppressor gene whose function is required for normal development of the genitourinary system. WT1 encodes a putative transcriptional repressor of the zinc finger family. Here we discuss how one of the normal functions of WT1 may be to suppress myogenesis during kidney development. Furthermore, we describe how we are proposing to use YAC (yeast artificial chromosome) transgenesis to analyse WT1 regulation and function in mice. We also discuss the evolution of the WT1 gene amongst different vertebrate classes and how this may provide insights into genitourinary evolution. PMID- 7883784 TI - Signal transduction by the macrophage-colony-stimulating factor receptor (CSF 1R). AB - The macrophage-specific colony-stimulating factor 1 (CSF-1 or M-CSF) is required throughout the G1 phase of the cell cycle to regulate both immediate and delayed early responses necessary for cell proliferation. These are triggered by the binding of the growth factor to the colony-stimulating factor 1 receptor and the activation of its intrinsic tyrosine-specific protein kinase. Phosphorylation of the colony-stimulating factor 1 receptor on specific tyrosine residues enables it to bind directly to cytoplasmic effector proteins, which in turn relay receptor induced signals through multiple-signal transduction pathways. The activity of p21ras as well as transcription factors of the ets gene family appears to be required for colony-stimulating factor 1 to induce the c-myc gene, and the latter response is essential to ensure cell proliferation. Genes within the fos/jun or activator protein 1 family are targeted via a parallel and independently regulated signal transduction pathway. The continuous requirement for colony stimulating factor 1 after the immediate early response is initiated indicates that expression of additional delayed early response genes, although contingent on previously induced gene products, might also depend on colony-stimulating factor 1-induced signals. Among the growth factor-regulated delayed early response genes are D-type G1 cyclins, which play an important role in cell-cycle progression. PMID- 7883785 TI - Focal adhesion kinase: structure and signalling. AB - Studies on the attachment and spreading of cells in culture have provided valuable insights into the mechanisms by which cells transmit information from the outside to the inside of the cell. This brief review considers recent information on the role of focal adhesion-associated protein tyrosine kinases in integrin-regulated cell signalling. PMID- 7883786 TI - Regulation and function of the MAP kinase cascade in Xenopus oocytes. AB - In Xenopus oocytes, activation of MAP kinase occurs during meiotic maturation through a protein kinase cascade (the MAP kinase cascade), which is utilized commonly in various intracellular signaling pathways in eukaryotes. Studies with a neutralizing antibody against Xenopus MAP kinase kinase (MAPKK), a direct upstream activator for MAP kinase, have shown that the MAP kinase cascade plays a crucial role in both initiating oocyte maturation and inducing metaphase arrest. PMID- 7883787 TI - Signal transduction through the GTP-binding proteins Rac and Rho. AB - Actin reorganization is an early response to many extracellular factors. In Swiss 3T3 fibroblasts, the Ras-related GTP-binding proteins Rho and Rac act as key signal transducers in these responses: Rho is required for growth factor-induced formation of stress fibres and focal adhesions, whereas membrane ruffling is regulated by Rac proteins. Several proteins that act as GTPase activating proteins (GAPs) for Rho-related proteins have been identified, and these could act either as targets or down-regulators of Rho or Rac in cells. In vitro, the GAP domain of p190 has a striking preference for Rho as a substrate, and when microinjected into Swiss 3T3 cells it inhibits stress fibre formation but not membrane ruffling induced by growth factors. BcrGAP acts on Rac but not Rho in vitro, and specifically inhibits membrane ruffling in vivo. Finally, RhoGAP acts preferentially on the Rho-related protein G25K/Cdc42Hs in vitro, but can inhibit Rho-mediated responses in vivo. These results suggest that p190, Bcr and RhoGAP play specific roles in signalling pathways through different Rho family members. The mechanisms underlying Rho-regulated stress fibre formation have been investigated further by analysing the role of other signals known to be activated by lysophosphatidic acid (LPA). Neither activation of PK-C, increased intracellular Ca2+, decreased cAMP levels or Ras activation appear to mediate stress fibre formation. However, LPA stimulates tyrosine phosphorylation of a number of proteins, including the focal adhesion kinase, pp125FAK, and genistein, a tyrosine kinase inhibitor, prevents this increase in tyrosine phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883788 TI - The role of the p53 and Rb-1 genes in cancer, development and apoptosis. AB - Gene targeting using embryonal stem cells has been used to generate strains of mice with inactivating mutations at the Rb-1 and p53 tumour suppressor loci. Mice heterozygous for a null allele of Rb-1 do not show retinoblastomas but instead develop pituitary tumours. Homozygotes die at between 10 and 14 days' gestation and show increased levels of both cell division and cell death by apoptosis in the haematopoietic and nervous systems. This is consistent with the view that the Rb-1 gene product plays a general role in the maturation of precursor cells. In contrast, mice heterozygous for a null allele of p53 are predisposed to a spectrum of tumours, while the corresponding homozygotes are viable but show a very high tumour incidence. Thymocytes from p53 homozygotes, unlike wild-type thymocytes, do not show increased levels of apoptosis following treatment with DNA-damaging agents, while response to its induction by other agents is unaltered. Similarly, epithelial cells from the crypts of both small and large intestine of p53-deficient mice are resistant to the induction of apoptosis by gamma-irradiation. In contrast, two other early responses of wild-type crypts to gamma-irradiation, namely the G2 block and the reduction in bromodeoxyuridine incorporation, are both largely intact in p53-deficient mice. These observations are consistent with the view that p53 is responsible for monitoring DNA damage so that damaged cells can be either repaired or eliminated prior to division. PMID- 7883789 TI - Drosophila in cancer research: the first fifty tumor suppressor genes. AB - In Drosophila, over 50 genes have been identified in which loss-of-function mutations lead to excess cell proliferation in the embryo, in the central nervous system, imaginal discs or hematopoietic organs of the larva, or in the adult gonads. Twenty-two of these genes have been cloned and characterized at the molecular level, and nine of them show clear homology to mammalian genes. Most of these mammalian genes had not been previously implicated in cell proliferation control. Overgrowth in some of the mutants involves conversion to a cell type that, in normal development, shows more cell proliferation than the original cell type. Thus the neurogenic mutants, including Notch, show conversion of epidermal cells to neuroblasts, leading to the 'neurogenic' phenotype of excess nervous tissue. The ovarian tumor mutants show conversion of the female germ line to a cell type resembling the male germ line, which undergoes more proliferation than the female germ line. Mutations of the fat locus cause hyperplastic overgrowth of imaginal discs, in which the epithelial structure is largely intact. The predicted fat protein product is a giant relative of cadherins, supporting indications from human cancer that cadherins play an important role in tumor suppression. Mutations in the lethal(2)giant larvae and lethal(1)discs large genes cause neoplastic overgrowth of imaginal discs as well as the larval brain. The dlg gene encodes a membrane-associated guanylate kinase homolog that is localized at septate junctions between epithelial cells. This protein is a member of a family of homologs that also includes two proteins found at mammalian tight junctions (ZO-1 and ZO-2) and a protein found at mammalian synaptic junctions (PSD-95/SAP90). Genes in which mutations cause blood cell overproduction include aberrant immune response-8, which encodes the RpS6 ribosomal protein and hopscotch, which encodes a putative non-receptor protein tyrosine kinase. The gene products identified by ovarian tumor mutants do not show clear amino acid sequence homology to known proteins. Drosophila provides an opportunity to rapidly identify and characterize tumor suppressor genes, many of which have mammalian homologs that might also be involved in cell proliferation control and tumor suppression. PMID- 7883790 TI - Pax genes in development. AB - The Pax gene family consists of nine members encoding nuclear transcription factors. Their temporally and spatially restricted expression pattern during embryogenesis suggests that they may play a key role during embryogenesis. Direct evidence for the important role of the Pax genes during embryonic development has been demonstrated by the correlation of mouse developmental mutants and human syndromes with mutations in some Pax genes. To date three Pax genes have been shown to be mutated in undulated, Splotch and small eye, respectively. In man, Pax-3 is mutated in the Waardenburg syndrome, while in aniridia Pax-6 is mutated. PMID- 7883791 TI - Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes and Hirschsprung disease. AB - Distinct point mutations in the RET proto-oncogene are the cause of the inherited multiple endocrine neoplasia type 2 syndromes (MEN 2), and the congenital gut disorder Hirschsprung disease. The site and type of these mutations suggests that they have differing effects on the activity of the receptor tyrosine kinase encoded by RET. The normal function of the RET receptor tyrosine kinase has yet to be determined. However, this has been investigated by the inactivation of the RET gene in transgenic mice. The developmental abnormalities apparent in these mice, together with the observation that the major tissues affected in MEN 2 and Hirschsprung disease have a common origin in the embryonal neural crest, suggest that RET encodes a receptor for a developmental regulator involved in the genesis of a variety of neural crest derivatives, and in the organogenesis of the kidney. PMID- 7883792 TI - bcl-2 in cancer, development and apoptosis. AB - The bcl-2 gene provides a window on the basic cellular machinery of apoptosis or programmed cell death, a process involved in virtually all biologic events in multicellular organisms, but particularly relevant to neoplasia and development. bcl-2 gene function supports cell survival and appears to lie at a nodal point in pathways leading to activation or execution of apoptosis. Carcinogenesis may involve several steps at which cell death programs are normally activated and are bypassed in cancer cells, including apoptotic pathways activated by several oncogenes. Functional redundancy and the complexity of the regulation of cell survival are demonstrated by the less than expected phenotype of bcl-2 knockout mice and the cloning of several bcl-2 related genes, some of which promote cell death. The molecular function for bcl-2 is unknown, but several lines of evidence support a role in protection from oxidative stress. These studies suggest that many environmental perturbations and genetic pathways converge to disrupt a metabolic balance between oxidant generation and anti-oxidant defenses. PMID- 7883793 TI - Coupling of DNA replication and mitosis by fission yeast rad4/cut5. AB - The fission yeast cut5+ (identical to rad4+) gene is essential for S phase. Its temperature-sensitive (ts) mutation causes mitosis while S phase is inhibited: dependence of mitosis upon the completion of S phase is abolished. If DNA is damaged in mutant cells, however, cell division is arrested. Thus the checkpoint control system for DNA damage is functional, while that for DNA synthesis inhibition is not in the cut5 mutants. Transcription of the cut5+ gene is not under the direct control of cdc10+, which encodes a transcription factor for the START of cell cycle. The transcript level does not change during the cell cycle. The protein product has four distinct domains and is enriched in the nucleus. Its level does not alter during the cell cycle. The N-domain is important for cut5 protein function: it is essential for complementation of ts cut5 mutations and its overexpression blocks cell division. Furthermore, it resembles the N-terminal repeat domain of proto-oncoprotein Ect2, which, in the C-domain, contains a regulator-like sequence for small G proteins. We discuss a hypothesis that the cut5 protein is an essential component of the checkpoint control system for the completion of DNA synthesis. The restraint of mitosis until the completion of S phase is mediated by the cut5 protein, which can sense the state of chromosome duplication and negatively interacts with M phase regulators such as cdc25 and cdc2. PMID- 7883794 TI - Regulation of the cell cycle timing of Start in fission yeast by the rum1+ gene. AB - We have identified the rum1+ gene as a new regulator of the G1-phase of the fission yeast cell cycle. rum1+ determines the cell cycle timing of Start, by maintaining cells in a pre-Start state until they have attained a minimal critical mass. Cells lacking rum1+ are unable to arrest in pre-Start G1 in response to nitrogen starvation and are subsequently sterile. In addition, rum1+ prevents entry into mitosis from pre-Start G1, as shown by the fact that cdc10 mutants in the absence of rum1+ undergo lethal mitosis without entering S-phase. PMID- 7883795 TI - G1 control in mammalian cells. AB - Cyclin-dependent kinases (Cdks) control the major cell cycle transitions in eukaryotic cells. On the basis of a variety of experiments where cyclin function either is impaired or enhanced, D-type cyclins as well as cyclins E and A have been linked to G1 and G1/S phase roles in mammalian cells. We therefore sought to determine if agents that block the G1/S phase transition do so at the level of regulating the Cdk activities associated with these cyclins. A variety of conditions that lead to G1 arrest were found to correlate with accumulation of G1 specific Cdk inhibitors, including treatment of fibroblasts with ionizing radiation, treatment of epithelial cells with TGF-beta, treatment of HeLa cells with the drug lovastatin, and removal of essential growth factors from a variety of different cell types. Mechanistically, inhibition of Cdks was found to involve the stoichiometric binding of Cdk inhibitor proteins. p21Waf1/Cip1 was associated with DNA damage induced arrest while p27Kip1/p28Ick1 accumulated under a variety of antiproliferative conditions. PMID- 7883796 TI - A developmental context for multiple genetic alterations in Wilms' tumor. AB - Wilms' tumor has served as an example of Knudson's two-hit hypothesis of recessive tumor genes, but the genetics has proven to be surprisingly complex. WT1, a tumor suppressor gene on 11p13, is mutated in only a small fraction of Wilms' tumors, and a second chromosomal region, 11p15, harbors a second Wilms' tumor gene also involved in other cancers. In addition, loss of genomic imprinting, or parental origin-specific gene expression of at least two genes, appears to be an early step in Wilms' tumorigenesis and common cancers. Finally, genes on other chromosomes also play a role. I propose a model of Wilms' tumorigenesis in which multiple genetic alterations act within a specific developmental context, accounting for the epidemiological and pathological heterogeneity of Wilms' tumor, as well as the tissue specificity of the tumor types arising from alterations in these genes. PMID- 7883797 TI - The role of cdc25 in checkpoints and feedback controls in the eukaryotic cell cycle. AB - Major checkpoints that gate progression through the cell cycle function at the G1/S transition, entry into mitosis and exit from mitosis. Cells use feedback mechanisms to inhibit passage through these checkpoints in response to growth control signals, incomplete DNA replication or spindle assembly. In many organisms, transition points seem to involve regulation of the activity of cyclin dependent kinases (cdks) not only through their interactions with various cyclins, but also by phosphorylation-dephosphorylation cycles acting on the kinase activity of the cdks. These phosphorylation cycles are modulated by the regulation of the opposing kinases and phosphatases that act on cdks and form feedback loops. In this article, we discuss the role of positive and negative feedback loops in cell cycle timing and checkpoints, focusing more specifically on the regulation of the dual specificity cdc25 phosphatase. PMID- 7883798 TI - pRB, p107 and the regulation of the E2F transcription factor. AB - Small DNA tumor viruses, such as adenovirus, encode proteins that deregulate the cell cycle. These proteins are potent transforming agents when tested in standard oncogenic assays. For adenovirus the best characterized viral oncoproteins are the early region 1A (E1A) products. Mutational studies have shown that E1A's oncogenic ability is determined primarily by its ability to bind to certain cellular proteins and interfere with their function. One of these cellular targets for E1A is the product of the retinoblastoma tumor suppressor gene, pRB. pRB is a negative regulator of cell proliferation, and its inactivation has been shown to be an important oncogenic step in the development of many human cancers. In adenovirusmediated transformation, E1A binds to pRB and inactivates it, thus functionally mimicking the loss of pRB often seen in human tumors. There is now compelling evidence to suggest that pRB regulates transcription at specific phases of the cell cycle by physically associating with key transcription factors. The best characterized target of pRB is the transcription factor E2F. The interaction of pRB and E2F leads to the inhibition of E2F-mediated transactivation. Most of the genes that are known to be controlled by E2F have key roles in the regulation of cell proliferation. During cell cycle progression, phosphorylation of pRB appears to change its conformation and E2F is released. In pathogenic settings E2F transactivation is not regulated by pRB binding. In human tumors with mutations in the retinoblastoma gene, functional pRB is absent and hence can no longer inhibit E2F activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7883799 TI - The D-type cyclins and their role in tumorigenesis. AB - The D-type cyclins are expressed during the progression from G0/G1 to S phase in the mammalian cell cycle. There is considerable evidence that they contribute to the development of specific cancers, both in humans and in mouse models. For example, cyclin D1 can be activated by chromosomal translocation, DNA amplification and retroviral integration. Cyclins D1, D2 and D3 preferentially associate with two closely related members of the cyclin-dependent kinase family, Cdk4 and Cdk6 and the various complexes are each capable of phosphorylating the retinoblastoma gene product (pRb), at least in vitro. This suggests that the growth promoting effects of the D-cyclins may be manifest via their interactions with tumour suppressor genes. PMID- 7883800 TI - Structure and function of SH2 domains. AB - In order for cells to respond to their environment, a series of regulated molecular events has to take place. External signalling molecules bind to cellular receptors and thereby trigger the activation of multiple intracellular pathways, which modify cellular phenotypes. The cell-surface receptors for a wide range of polypeptide hormones possess protein tyrosine kinase activity, which is induced by binding of the appropriate extracellular ligand. Tyrosine phosphorylation can act as a molecular switch, by initiating the recruitment of cytoplasmic effector molecules containing Src homology (SH) 2 domains, to activated receptors. These SH2-containing proteins, in turn, regulate intracellular signalling pathways. Here, we discuss the role of tyrosine phosphorylation in triggering signalling pathways, as well as the functions of SH2 domains, which mediate these events through phosphotyrosine-dependent protein protein interactions. PMID- 7883801 TI - An unusual cause of pulmonary embolism in a young man. PMID- 7883802 TI - Apocalypse. PMID- 7883803 TI - Myocardial injury: anterior and inferior? PMID- 7883804 TI - Case in point. Lymphogranuloma venereum. PMID- 7883806 TI - A checklist for contracts. PMID- 7883805 TI - Mixed cryoglobulinemia and hepatitis C virus. AB - HCV appears to cause chiefly an asymptomatic chronic infection, which is nonetheless linked to a heightened prevalence of "essential" mixed cryoglobulinemia. The monoclonal rheumatoid factor occurring in the disease may result from chronic stimulation of the immune system, perhaps by the virus directly. PMID- 7883807 TI - Refining our management of asthma. PMID- 7883808 TI - Syncope in a middle-aged man at work. PMID- 7883809 TI - Unexplained hemothorax, hemarthrosis, and palpable purpura. PMID- 7883810 TI - A practical approach to nephrolithiasis. AB - Detailed metabolic evaluation and prophylaxis for all patients presenting with a first renal stone seems inappropriate. The crucial clinical problem lies in predicting which patients are likely to have a recurrence. Stone composition is an important guide for the physician's decisions concerning investigation and a rational choice of treatment. PMID- 7883811 TI - Deep vein thrombosis: recovery or recurrence? AB - As many as two thirds of patients with new symptoms after documented DVT have postphlebitic syndrome, not DVT. Noninvasive imaging is central to the differentiation so that unnecessary anticoagulation therapy can be avoided. Recent changes in heparin and warfarin protocols for DVT are also outlined. PMID- 7883812 TI - Penicillin for streptococcal pharyngitis: has anything changed? AB - It used to be simple: A single IM injection or 10 days of oral therapy would cure the sore throat and prevent rheumatic fever. Post-treatment carriage of group A does not seem to be adequate reason to switch strategies today. PMID- 7883813 TI - Recurrent cellulitis complicating chronic lymphedema. PMID- 7883814 TI - Drugs or ablation for supraventricular tachycardia? PMID- 7883815 TI - Individualizing drug therapy for the hypertensive patient. AB - When prescribing antihypertensive agents, the clinician must take into account coexisting conditions, lest treatment produce adverse, perhaps even life threatening, side effects. The preferred agents and those to be avoided are discussed for six associated pathologies. Available drug options now permit tailored therapy that not only lowers blood pressure but also minimizes organ damage. PMID- 7883816 TI - Expression of epidermal growth factor, transforming growth factor-alpha, and their common receptor genes in human umbilical cords. AB - Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha), present in amniotic fluid and/or in fetal blood, could potentially regulate cord functions. The present study investigated the possible presence of functional receptors and EGF and TGF alpha themselves in umbilical cord. The reverse transcription-polymerase chain reaction followed by Southern blotting demonstrated that human umbilical cords contain EGF, TGF alpha, and EGF/TGF alpha messenger ribonucleic acid (mRNA) transcripts. In situ hybridization revealed that these mRNA transcripts are present in vascular endothelial cells and smooth muscle, amnion, and myofibroblasts in Wharton's jelly. Western immunoblotting showed that the cords contain a 170-kilodalton EGF/TGF alpha receptor protein. Immunocytochemistry demonstrated that all of the cells that contained mRNA transcripts also contained corresponding proteins. Umbilical amnion contains more EGF, TGF alpha, and their receptors than any other part of the cord. In the cord, the fetal and middle portions contain more than the placental portion or the vessels inside the placental tissue. The cord receptors can bind [125I]EGF, stimulate receptor autophosphorylation, and increase cyclooxygenase-1 and -2 and prostaglandin E2, suggesting that the receptors are functional. In summary, our study demonstrates that human umbilical cord expresses EGF, TGF alpha, and their common receptor genes. The cord EGF/TGF alpha receptors are functional in terms of binding of EGF, activation of receptor autophosphorylation, and increasing the formation of vasoconstrictive eicosanoid. Thus, EGF, TGF alpha, and their receptors could be one of the determinants of human fetal growth and development by autocrine, paracrine, and endocrine actions in umbilical cord. PMID- 7883817 TI - Immunocytochemical analyses of dehydroepiandrosterone sulfotransferase in cultured human fetal adrenal cells. AB - Dehydroepiandrosterone sulfate is the major steroid secretory product of the human fetal adrenal gland. Several factors have been shown to modulate the secretion of this steroid by cultured fetal adrenal cells. In addition to the cytochrome P450 enzymes that are important in steroid biosynthesis, dehydroepiandrosterone sulfotransferase (DST) is likely to be a key regulated enzyme in the formation of sulfated steroids, which are characteristic of the human adrenal cortex, particularly that of the fetus and the adult zona reticularis. In the present investigation, we sought to evaluate the cellular localization of DST in cultures derived from the fetal zone, neocortex, and adrenal capsule and to determine the effects of ACTH and other agonists of the protein kinase-A pathway on the abundance of DST in such cells. Cells derived from the fetal zone, neocortex, and adrenal capsule were either precultured for 3 13 days in plastic flasks followed by culture on coverslips or were cultured directly on coverslips in control medium (McCoy's 5A medium that contained 5% fetal bovine serum) or control medium plus ACTH, forskolin, or dibutyryl cAMP for 1-4 days. Cells were fixed in buffered formalin and then immunostained for DST by use of a rabbit polyclonal antiserum prepared against human liver DST. DST immunoreactivity was abundant in freshly isolated cortical cells derived from fetal zone and neocortex. DST immunoreactivity was still observable in fetal zone and neocortex cells as well as in cells prepared from enzymatic digests of adrenal capsule after scraping off adherent neocortex cells following culture for 9-14 days in control medium. Adrenal fibroblasts were negative for DST. DST abundance in cortical cells was increased in cultures supplemented with ACTH, forskolin, or dibutyryl cAMP compared to that in cultures grown in control medium alone. The results of Western blot analyses of DST in these cells were consistent with the immunocytochemical data. These results suggest that DST is present in both fetal zone and neocortex cells of the human fetal adrenal at midgestation and that the production of DST is stimulated by ACTH and agonists of the protein kinase-A signal transduction pathway in the human fetal adrenal gland. PMID- 7883818 TI - Lack of association between a polymorphism in the coding region of the thyrotropin receptor gene and Graves' disease. AB - Using a combination of polymerase chain reaction amplification, oligonucleotide mismatch hybridization, and direct sequencing, we analyzed the distribution of a recently described TSH receptor gene polymorphism in 88 patients with Graves' disease but no clinically apparent eye disease, 53 patients with Graves' disease and associated ophthalmopathy, 39 patients with autoimmune hypothyroidism, and 156 control subjects. No significant difference in the distribution of this polymorphism was found between either group of Graves' patients, the hypothyroid patients, or the control group. These results suggest that this coding region polymorphism is not associated with the occurrence of Graves' disease or Graves' ophthalmopathy. PMID- 7883819 TI - Intraoperative measurement of adrenocorticotropin (ACTH) during removal of ACTH secreting bronchial carcinoid tumors. AB - The optimal treatment for ectopic ACTH syndrome is the complete removal of the tumor secreting ACTH. These tumors are often occult, with their location suggested but not proven with imaging techniques. The intraoperative measurement of ACTH by immunoradiometric assay in five patients with the occult ectopic ACTH syndrome during removal of suspicious intrapulmonary lesions is reported. A significant ACTH gradient was detected in the pulmonary veins of the affected lobes in two patients. ACTH had decreased significantly in all five patients by 10 and 15 min after tumor removal. All five patients had histologically proven ACTH-secreting bronchial carcinoid tumors, suppressed plasma ACTH by 24 h after tumor removal, and subsequent secondary adrenal insufficiency indicating successful surgical therapy (five of five true-positive). In one patient, previous surgery was not curative and did not result in a decrease in intraoperative measurement of ACTH (one of one true-negative). It was demonstrated that a rapid ACTH immunochemiluminescence assay with a 15-min incubation time has sufficient sensitivity and precision to detect decreases in ACTH described above. These results demonstrate that complete removal of ACTH secreting bronchial carcinoid tumors can be detected intraoperatively by a decrease in arterial ACTH by 15 min. The modification of the ACTH immunochemiluminescence assay to 15 min incubation allows the documentation of a successful tumor removal in the operating room. It may also be used to locate the tumor intraoperatively by selective pulmonary vein sampling. This protocol may be applicable to the intraoperative measurement of ACTH during pituitary microadenomectomy for Cushing's disease. PMID- 7883820 TI - Artificial mutations in P450c11AS (aldosterone synthase) can increase enzymatic activity: a model for low-renin hypertension? AB - The conversion of 11-deoxycorticosterone (DOC) to aldosterone is catalyzed by a single enzyme, termed P450c11AS, which has 11 beta-hydroxylase, 18-hydroxylase and 18-oxidase activities. The normotensive Dahl salt-resistant (R) rat has two mutation in P450c11AS that increase its aldosterone synthase activity. If such a mutation were to occur in human patients the predicted phenotype would be low renin hypertension with elevated ratios of plasma aldosterone to plasma renin activity. Before searching for P450c11AS mutations in such patients we sought to determine if mutations in human P450c11AS could increase enzymatic activity in a fashion analogous to the Dahl R rat. We used site-directed mutagenesis of the human P450c11AS cDNA to create the mutants Glu 136-->Asp, Lys 251-->Arg and the combination of the two; these mutations correspond to those seen in the Dahl R rat. Cells transfected with these mutant human P450c11AS sequences could convert [14C]DOC to corticosterone, 18OH-corticosterone, and aldosterone. In particular the Lys 251-->Arg mutant produced 4 times as much 18OH-corticosterone and 50-80% more aldosterone than the wild type. These data show that mutations of human P450c11AS can increase enzymatic activity, suggesting that such mutations could, in theory, be the basis of some forms of human low-renin hypertension. PMID- 7883821 TI - Clinical review: 67: Approach to chemoprevention of prostate cancer. PMID- 7883822 TI - Bones of contention: the problem of mild hyperparathyroidism. PMID- 7883823 TI - Longitudinal measurements of bone density and biochemical indices in untreated primary hyperparathyroidism. AB - A large number of patients with primary hyperparathyroidism today do not undergo parathyroidectomy. In this prospective study, we evaluated the effect of untreated disease on biochemical and bone densitometric indices. In 66 patients, seven annual measurements showed no change in serum calcium, phosphorus, PTH, vitamin D, or alkaline phosphatase; in urinary calcium, hydroxyproline or hydroxypyridinium cross-link excretion; or lumbar spine, femoral neck, and radial bone mineral density. The subset of postmenopausal women also showed no change in biochemical indices or bone density at any of the three sites. Twenty-four patients met guidelines for surgery as established by the NIH Consensus Conference, 1990. They differed from those who did not meet these guidelines only by being younger (50 +/- 3 vs. 62 +/- 2 yr; P = 0.0005) and by having higher urinary calcium excretion [7.7 +/- 0.9 vs. 5.4 +/- 0.3 mmol/L (310 +/- 37 vs. 215 +/- 14 mg/g creatinine); P < 0.01]. No longitudinal changes in biochemical profile or bone mineral density at any site were noted in this subgroup. Conservative management of patients with mild primary hyperparathyroidism does not lead to progression of disease, as reflected by biochemical indices. Bone density is maintained over 6 yr of observation at sites reflecting both cortical (radius) and cancellous (lumbar spine) bone. PMID- 7883824 TI - Increased bone mineral density after parathyroidectomy in primary hyperparathyroidism. AB - Skeletal involvement in primary hyperparathyroidism is characterized by preferential loss of cortical bone, whereas cancellous bone is relatively spared. Little data are available concerning changes in bone density, particularly at sites containing more cancellous bone, after successful parathyroidectomy. Most patients with primary hyperparathyroidism are asymptomatic, but approximately 50% meet one or more criteria for surgery. In a prospective study of 34 patients who met one or more such criteria, bone density rose at all skeletal sites (lumbar spine, femoral neck, and the radius) in the 4 yr after surgery. The lumbar spine, with most cancellous bone, showed a rapid (mean +/- SE, yr 1, 8.2 +/- 2.0%; P < 0.005) and sustained (yr 4, 12.8 +/- 2.8%; P < 0.001) rise. Post-menopausal patients were similar (by yr 4, 12.5 +/- 2.7%; P < 0.005). At the femoral neck, with intermediate cancellous and cortical composition, a similar increase was noted (12.7 +/- 3.8% by yr 4; P < 0.01). The distal radius, containing mostly cortical bone, rose modestly (4.0 +/- 1.5% by yr 3; P < 0.05), except in patients with lowest preoperative bone density, where the increase was marked (12.3 +/- 2.6% by yr 3; P < 0.05). In patients meeting surgical guidelines, parathyroidectomy is associated with improved bone mineral density. PMID- 7883825 TI - 21-deoxyaldosteronism: a new clinical syndrome. PMID- 7883826 TI - A new subset of mineralocorticoid hypertension with excess of 21-deoxyaldosterone and Kelly's-M1 steroid: clinical and morphological findings. AB - Ten cases of adrenal adenomas, one case with unilateral adrenal hyperplasia, and another case with apparent bilateral are reported, in whom an alternative pathway of aldosterone via 21-deoxyaldosterone is operative. They all manifested hypertension, low renin activity, low normal potassium values, as well as high urinary excretion rates of 21-deoxyaldosterone and its related metabolite Kelly's M1 steroid. In all cases, urinary aldosterone metabolites (aldosterone-18 glucuronide and tetrahydroaldosterone) and aldosterone precursor 18 hydroxycorticosterone levels were normal. Hence, the adrenal lesions give rise to hyper-21-deoxyaldosteronism. 21-Deoxyaldosterone is a weak mineralocorticoid, and its elevated production in the presence of normal aldosterone can induce a pathological state of hypermineralocorticoidism. Adrenalectomy resulted in normalization of hypertension in six of eight and amelioration in two of eight cases. Six of seven adenoma cases examined as well as the case of unilateral adrenal hyperplasia were sensitive to ACTH. One of the seven adenomas and, as expected, the case with apparent bilateral hyperplasia were angiotensin responsive. Histologically and electron microscopically, the operated adenomas consisted predominantly of clear cells, characterized by mitochondria with tubulo vesicular internal structure similar to those of the zona fasciculata (in contrast, our classical Conn's adenoma with normal 21-deoxyaldosterone excretion exhibited a more heterogenous histological appearance and were, in terms of ultrastructure, more similar to cells of the zona glomerulosa). Ultrastructurally and immunocytochemically, the clear cells of 21-deoxyaldosterone adenomas showed features of both the zona glomerulosa and the zona fasciculata and are, hence, considered to be hybrid cells. We conclude that the determination of 21 deoxyaldosterone and Kelly's-M1 should be considered in the diagnosis of mineralocorticoid-induced forms of hypertension, especially when an adrenal adenoma has been detected with an imaging procedure. PMID- 7883827 TI - Extensive personal experience: the clinical evaluation and management of osteoporosis. PMID- 7883828 TI - Corticosteroid-binding globulin modulates cortisol concentration responses to a given production rate. AB - In most clinical situations, the ability of the adrenal to produce cortisol is studied with measurements of cortisol concentration. The validity of this assumes the existence of a predictable relationship between cortisol production and plasma cortisol concentration. This assumption was tested by determining if production rates, as simulated by constant cortisol infusions, were predictive of the resultant plasma and urine cortisol concentrations in dexamethasone suppressed subjects. Additional attempts to predict simulated cortisol production rates were made with infusions of [9,12,12-2H3]cortisol. Thirty-six 8-h cortisol infusions were performed in 24 subjects. Although there was a tendency to achieve a higher plasma cortisol concentration response at a higher cortisol infusion rate (P < 0.04), the known cortisol infusion rate was a poor predictor of plasma cortisol responses (r2 = 0.12). Addition of corticosteroid-binding globulin concentration (CBG) as a covariate greatly improved the predictability of plasma cortisol responses (r2 = 0.52). Urine free cortisol, normalized to inulin excretion, had a predictable relationship to cortisol infusion rate (r2 = 0.82). Isotope-enrichment data from a group of 6 subjects receiving multiple cortisol infusions during administration of [9,12,12-2H3]cortisol gave the most accurate predictions of the known cortisol infusion rates (r2 = 0.93). It is concluded that: 1) cortisol infusion (production) rate and plasma cortisol concentration are poorly correlated; 2) CBG is an important modulator of concentration responses to a given production rate; and 3) short (8-h) infusions of [9,12,12 2H3]cortisol may be used to determine cortisol production rates in humans. The mechanisms by which CBG modulates cortisol concentration responses are elaborated in a companion report. PMID- 7883829 TI - Corticosteroid-binding globulin influences kinetic parameters of plasma cortisol transport and clearance. AB - In an accompanying study, we reported a very poor correlation between the magnitude of a continuous cortisol infusion in dexamethasone-suppressed adults and the resultant steady state plasma cortisol concentration (r2 = 0.13). The concentration of corticosteroid-binding globulin (CBG) was found to explain an additional 39% of the variance in cortisol response. We hypothesized that CBG might act by altering kinetic parameters of cortisol transport. According, the rate of cortisol disappearance (Kd), volume of distribution (V), and pool size (P) were determined after bolus injection of a stable isotope of cortisol in two groups of healthy female subjects with both normal and elevated CBG concentrations. The bolus studies were performed during continuous cortisol infusion and steady state conditions of plasma cortisol concentration. Two models were used to generate the kinetic parameters. The kinetic parameters thus generated were able to predict the known cortisol infusion rate with 4-16% error. The goodness of fit of modeled to experimental data was excellent in all cases (> 0.93). In both models, Kd had a negative correlation to the CBG concentration (P < 0.05), a negative correlation to the volume of distribution (P < 0.03), and a positive correlation (P < 0.03) to pool size. Excellent correlations were noted between both models in estimates of kinetic parameters (r2 = 0.82-0.97; P < 0.01). We conclude that CBG, in addition to its role of transport protein, plays an active role in determining the disposition of cortisol in humans. PMID- 7883830 TI - Estrogen action on the bone mass of postmenopausal women is dependent on body mass and initial bone density. AB - Recent evidence suggests that estrogen replacement therapy (ERT) may be effective in preventing bone loss even in late postmenopausal women. We analyzed the role of age and other factors as determinants of ERT action on vertebral bone density (VBD) in 73 consecutive Caucasian postmenopausal women treated for 1 yr or longer. A group of 44 women who received calcium supplements only were analyzed as controls. VBD was measured every 6 months by dual energy x-ray absorptiometry, and yearly rates of change were calculated by linear regression for each subject. VBD increased in the estrogen-treated group (+17.32 +/- 2.84 mg/cm2.yr; 2.42 +/- 0.37%/yr) and did not significantly change in untreated subjects (-4.08 +/- 3.68 mg/cm2/yr; -0.60 +/- 0.58%/yr). Women older than 60 yr experienced greater, although not significant, increments compared to younger subjects (+3.23 +/- 4.03% vs. +1.42 +/- 3.00%/yr), as did women more than 10 yr postmenopausal compared to patients within 10 yr after the menopause (+3.38 +/- 4.11% vs. +1.19 +/- 2.70%/yr). Rates of VBD change were positively correlated with age (r = 0.29; P = 0.014), years since menopause (r = 0.33; P = 0.005), and body mass index (BMI; r = 0.35; P = 0.003) and negatively with estimated initial VBD (r = -0.23; P = 0.05). However, only the relationships between bone density changes and BMI (r = 0.33; P < 0.01) and estimated initial VBD (r = -0.26; P < 0.05) held in a partial correlation analysis. BMI and estimated initial VBD were the only significant predictive factors for response to ERT (r2 = 21%) in a multivariate regression model. Therefore, the response to ERT depends mostly on BMI and initial VBD. Women with large body frames and those with lower initial VBD respond better to estrogen than slender women with higher bone mass. PMID- 7883831 TI - Zona fasciculata-like cells determine the response of plasma aldosterone to metoclopramide and aldosterone synthase messenger ribonucleic acid level in aldosterone-producing adenoma. AB - The different responses of plasma aldosterone to ACTH and angiotensin II in aldosterone-producing adenoma (APA) is thought to be due to the various cellular compositions of the tumors. To investigate whether the dopaminergic regulation of aldosterone in APA is also dependent on the cellular types, we studied the effects of metoclopramide on plasma aldosterone in six patients with APA. The messenger RNA (mRNA) levels of aldosterone synthase (P450aldo), 11 beta hydroxylase (P450(11) beta), and 17 alpha-hydroxylase (P450(17) alpha) of APA and normal adrenal glands were determined by competitive polymerase chain reaction. After administration of metoclopramide (an antagonist of dopamine-2 receptor), the increment of plasma aldosterone correlated inversely with the percentage of zona fasciculata cells of APA. The mRNA level of P450aldo in the tumorous portion was much higher, whereas the levels of P450(11) beta and P450(17) alpha mRNAs were lower, than those of the nontumorous portion and normal adrenals. There was a correlation of the percentage of zona fasciculata cells in APA with the levels of P450aldo and P450(11) beta mRNAs, but not with P450(17) alpha mRNA. These results suggest that differential responsiveness of plasma aldosterone to metoclopramide may be due to various proportions of different cell types in APA that may have different expression of dopamine-2 receptor. In addition, this histologically dependent expression was present at the transcriptional level of the gene responsible for aldosterone biosynthesis. PMID- 7883832 TI - Is radiation-induced ovarian failure in rhesus monkeys preventable by luteinizing hormone-releasing hormone agonists?: Preliminary observations. AB - With the advent of cancer therapy, increasing numbers of cancer patients are achieving long term survival. Impaired ovarian function after radiation therapy has been reported in several studies. Some investigators have suggested that luteinizing hormone-releasing hormone agonists (LHRHa) can prevent radiation induced ovarian injury in rodents. Adult female rhesus monkeys were given either vehicle or Leuprolide acetate before, during, and after radiation. Radiation was given in a dose of 200 rads/day for a total of 4000 rads to the ovaries. Frequent serum samples were assayed for estradiol (E2) and FSH. Ovariectomy was performed later. Ovaries were processed and serially sectioned. Follicle count and size distribution were determined. Shortly after radiation started, E2 dropped to low levels, at which it remained, whereas serum FSH level, which was low before radiation, rose soon after starting radiation. In monkeys treated with a combination of LHRHa and radiation, FSH started rising soon after the LHRHa loaded minipump was removed (after the end of radiation). Serum E2 increased after the end of LHRHa treatment in the nonirradiated monkey, but not in the irradiated monkey. Follicle counts were not preserved in the LHRHa-treated monkeys that received radiation. The data demonstrated no protective effect of LHRHa treatment against radiation-induced ovarian injury in this rhesus monkey model. PMID- 7883833 TI - The effect of desipramine on basal and naloxone-stimulated cortisol secretion in humans: interaction of two drugs acting on noradrenergic control of adrenocorticotropin secretion. AB - Desipramine (DMI), a tricyclic antidepressant and norepinephrine (NE) reuptake blocker, is reported to induce ACTH and cortisol release acutely in humans, probably by facilitating central NE neurotransmission. Tricyclic antidepressant therapy, including DMI, normalizes the ACTH and cortisol hypersecretion that often accompanies depression. The mechanism of hypothalamic-pituitary-adrenal (HPA) axis inhibition by DMI in humans is unknown. In rats, DMI reduces the activity of the locus ceruleus, a major source of NE innervation of the hypothalamic paraventricular nucleus, the site of CRH neurons. Naloxone induces ACTH and cortisol release in humans through a noradrenergic-mediated mechanism and a probable consequent stimulation of hypothalamic CRH release. To study the interaction of these drugs on NE neurotransmission and, hence, HPA axis activity in humans, we administered DMI alone and with naloxone in a randomized, double blind, placebo-controlled protocol in eight healthy male volunteers. DMI (75 mg, orally) was given 180 min before naloxone (125 micrograms/kg BW, i.v.). Plasma ACTH and cortisol were measured at frequent intervals from 60 min before to 120 min after naloxone treatment. Plasma cortisol levels were 77% higher 180 min after DMI compared to those after placebo treatment (287 +/- 17 vs. 162 +/- 14 nmol/L; P = 0.000005). DMI reduced the naloxone-induced rise in cortisol (P = 0.02), but there was no change in the integrated cortisol response. The increase in basal plasma ACTH levels after DMI treatment did not reach statistical significance. DMI significantly increased systolic blood pressure and heart rate consistent with an effect on the noradrenergic control of the cardiovascular system. In summary, DMI increased basal cortisol levels consistent with facilitation of NE neurotransmission and, hence, hypothalamic CRH release. However, DMI had no enhancing effect on naloxone-induced cortisol release. This contrasts with the synergy observed when non-antidepressant agents that increase NE neurotransmission are given with naloxone to humans. DMI increases glucocorticoid feedback sensitivity in the rat HPA axis after several weeks through up-regulation of central corticosteroid receptors. However, this slowly developing effect is unlikely to occur during these acute studies. The effect of DMI on naloxone-induced cortisol release is consistent with an inhibitory effect on central noradrenergic control of ACTH release, perhaps at the locus ceruleus. This is the first human study to suggest an inhibitory effect of DMI on central noradrenergic control of ACTH release. PMID- 7883834 TI - Identification, molecular characterization, and cellular studies of an apolipoprotein E mutant (E1) in three unrelated families with hyperlipidemia. AB - Remnants of triglyceride-rich lipoproteins accumulate in plasma of subjects with type III hyperlipoproteinemia (HLP) due to defective clearance by hepatic receptors. Although most subjects with type III HLP are homozygous for apolipoprotein (apo) E2 (arg158-->cys, R158C), a variant that binds defectively to cell surface receptors, some individuals with type III HLP have rare mutations of apo E. We identified six subjects from three families with type III HLP who had either an apo E3/1 or E4/1 phenotype by isoelectric focusing. Using DNA restriction isotyping with HhaI, all six subjects were determined to have only one apo E allele encoding cys158 and the other encoding arg158. Subsequently, digestion of polymerase chain reaction-amplified portions of exon 4 of the apo E gene with endonucleases HaeIII, TaqI, and Sau3AI demonstrated a second DNA variant that encoded a single amino acid substitution (gly127-->asp, G127D) due to a guanosine-to-adenosine nucleotide change resulting in the apo E1 isoform (G127D, R158C), which had arisen from a parent apo E2 allele. This mutation was confirmed with direct DNA sequencing. Incubation of very low density lipoprotein (VLDL) isolated from hyperlipidemic apo E1 subjects with J774 macrophages resulted in a 7- to 12-fold increase in cellular cholesterol ester compared with VLDL from apo E2/2 subjects. Although heterozygosity for apo E1 alone did not impair the interaction of VLDL with cellular receptors in vitro, its presence in subjects with type III HLP suggests that apo E1, perhaps in combination with secondary factors, may be causative for the dyslipidemia. PMID- 7883835 TI - No apparent mineralocorticoid receptor defect in a series of sporadic cases of pseudohypoaldosteronism. AB - Pseudohypoaldosteronism (PHA) is characterized by congenital resistance of the kidney and/or other mineralocorticoid target tissues to aldosterone, resulting in excessive salt wasting. Although the mineralocorticoid receptor (MR) was suggested as a potential locus of the defect in this disease, no such abnormality was found in 3 recently reported cases, one of whom belongs to this series of 5 patients. Molecular studies of the MR complementary DNA and gene in this series of sporadic cases of pseudohypoaldosteronism are reported. Four of these patients had multiple mineralocorticoid target tissue resistance, whereas 1 had transient isolated resistance in the kidney. A nonconservative homozygous mutation (C944- >T944, Ala241-->Val241) was identified in the complementary DNA of 4 of the patients but was also found in 62 of 100 normal alleles. One of these 4 patients had an additional conservative heterozygous mutation (A760-->G760, Ileu180- >Val180), which was also present in 11 of 100 normal alleles. None of the patients had any abnormalities in the first untranslated exon and 0.9 kilobases of the 5'-regulatory region of the MR gene, which were fully sequenced and compared with the normal sequence. It is concluded that the mutations identified in 4 of these 5 patients with PHA are polymorphisms, which on their own have no apparent pathophysiological significance. It is hypothesized that the defect causing PHA might be in a post-MR step of aldosterone action or in an unsuspected nonclassic receptor for this hormone. PMID- 7883836 TI - The effect of alprazolam on serum cortisol and luteinizing hormone pulsatility in normal women and in women with stress-related anovulation. AB - Alprazolam, a benzodiazepine derivative, stimulates specific gamma-aminobutyric acidA receptors and has been found to inhibit CRH activity in the brain. This study examined the effect of alprazolam on serum cortisol and LH pulsatility in six women in the early follicular phase (EFP), six women in the midluteal phase (MLP), and six women with stress-related anovulation (SRA) of normal weight, but with a previous history of anorexia nervosa. Subjects were given alprazolam (2 mg, orally) or an identical placebo capsule at 0900 h, and blood samples were collected through an indwelling venous catheter every 10 min for 8 h in the SRA women and 10 h in EFP and MLP women. Women with SRA were also given clomiphene (100 mg/day) for 5 days before a further 8-h blood sampling session. As expected, there was a diurnal decline in serum levels of cortisol, which was significantly less in women with SRA (55 +/- 4%) than those in both EFP (76 +/- 4%) and MLP women (75 +/- 3%; P < 0.005). The food-related rise of cortisol that follows lunch in normal women was absent in women with SRA. Alprazolam accentuated the decline in serum cortisol, and in all three groups, the mean serum cortisol level after alprazolam treatment was significantly less (P < 0.05) than that after placebo. In SRA women, alprazolam restored visible LH pulses in all women and increased the mean LH pulse frequency (P < 0.02) and pulse amplitude (P < 0.05). This was associated with an increase in mean serum LH from 1.3 +/- 0.3 to 3.0 +/- 0.06 IU/L (P < 0.02). In EFP women, alprazolam reduced the frequency of LH pulsatility from a mean of 5.8 +/- 0.7 to 3.2 +/- 0.5 pulses/10 h (P < 0.02) and increased the mean pulse amplitude from 2.4 +/- 0.5 to 5.0 +/- 1.1 IU/L (P < 0.0005). Alprazolam had no significant effect on LH pulsatility or amplitude in MLP women. To explain this variation in response to alprazolam, we propose that alprazolam accelerates the GnRH pacemaker in SRA women by inhibiting excessive CRH activity, which blocks the GnRH pacemaker in these women. In normal women, we hypothesize that tonic inhibition of the GnRH pacemaker by CRH is minimal, and the reduced pulsatility of LH after alprazolam treatment in EFP women results from inhibition of stimulatory noradrenergic neurons. In MLP women, we propose that preexisting opioid inhibition of noradrenergic neurons by progesterone blocks this effect of alprazolam. PMID- 7883837 TI - The use of human recombinant gonadotropin receptors to search for immunoglobulin G-mediated premature ovarian failure. AB - Anti-FSH receptor antibodies, detected using animal systems, have been reported in a few patients with premature ovarian failure (POF). However, assays based on animal receptors may be inappropriate for detecting inhibiting antibodies in humans. Accordingly, we tested for interfering antibodies in patients with POF using a recombinant system expressing human (h) FSH and LH receptors. A mouse adrenal cell line transfected with the hFSH receptor (Y1-hFSHR) exhibits a dose dependent increase in progesterone when exposed to hFSH. An embryonal kidney cell line transfected with the hLH receptor gene (hLHR-293) exhibits a dose-dependent increase in cAMP when exposed to hLH. We isolated immunoglobulins G (IgG) from 38 patients with POF and 14 normal women. We stimulated Y1-hFSHR and hLHR-293 cells with hFSH or hLH in the presence of these IgG and determined the resulting progesterone or cAMP response. The progesterone and cAMP responses obtained in the presence of IgG from patients with POF did not differ significantly from the responses in the presence of IgG from normal women. In contrast, antigonadotropin polyclonal antibodies isolated in the same manner as the above IgGs caused a greater than 90% reduction in the response of the Y1-hFSHR and hLHR-293 cells. We did not detect inhibitory antibodies in any of our 38 patients with POF. Therefore, if blocking antibodies interfering with gonadotropin-receptor interaction are a mechanism for POF, they account for a small minority of cases (< 8%). PMID- 7883838 TI - Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo. AB - Endothelin-1 (ET-1) is a potent vasoactive and mitogenic peptide produced by the vascular endothelium. In this study, we evaluated whether insulin stimulates ET-1 secretion by human endothelial cells derived from umbilical cord veins and by human permanent endothelial hybrid cells Ea.hy 926. Moreover, to provide evidence that insulin may stimulate ET-1 secretion in vivo, plasma ET-1 levels were evaluated in 7 type II diabetic normotensive males (mean age, 54.3 +/- 4.0 yr) during 2-h hyperinsulinemic euglycemic clamps (287 pmol insulin/m2.min-1) as well as in 12 obese hypertensive males (mean age, 44.2 +/- 4.6 yr) before and after a 12-week period of caloric restriction. Our results showed that insulin stimulated ET-1 release from cultured endothelial cells in a dose-dependent fashion. ET-1 release persisted for 24 h and was also observed at physiological insulin concentrations (10(-9) mol/L). The insulin-induced ET-1 secretion was inhibited by genistein, a tyrosine kinase inhibitor, and by cycloheximide, a protein synthesis inhibitor, suggesting that it requires de novo protein synthesis rather than ET-1 release from intracellular stores. In the in vivo experiments, plasma ET-1 levels rapidly increased during euglycemic hyperinsulinemic clamps (from 0.76 +/- 0.18 pg/mL at time zero to 1.65 +/- 0.21 pg/mL at 60 min; P < 0.05) and persisted elevated until the end of insulin infusion (1.37 +/- 0.37 pg/mL at 120 min; P < 0.05 vs. time zero). In obese hypertensives, plasma ET-1 levels significantly decreased after 12 weeks of caloric restriction (from 0.85 +/- 0.51 to 0.48 +/- 0.28 pg/mL; P < 0.04). The decrease in body weight induced by caloric restriction was accompanied by a significant reduction in fasting insulin levels (from 167.2 +/- 94.0 to 98.9 +/- 44.9 pmol/L; P < 0.05) which correlated with the reduction in plasma ET-1 levels (r = 0.78; P < 0.003). In conclusion, our data show that insulin stimulates both in vitro and in vivo ET-1 secretion. Such interaction could play a significant role in the development of atherosclerotic lesions in hyperinsulinemic conditions. PMID- 7883839 TI - Sustained therapy with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors does not impair steroidogenesis by adrenals and gonads. AB - Plasma lipoproteins are a major source of cholesterol for steroid hormone synthesis. 3-Hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitors, which reduce both intracellular cholesterol synthesis and serum cholesterol levels, thus have a potential negative impact on steroidogenesis. In this study, we evaluated basal and maximally stimulated adrenocortical and testicular steroidogenesis in 24 hypercholesterolemic male subjects during 6-36 months of statin treatment. One group was evaluated before treatment and after 6 months of treatment. A second group, which received long term treatment, was evaluated after 24-36 months and then 2 months after treatment had been discontinued. Fourteen subjects were given simvastatin, and 12 were given pravastatin, both at the maximum therapeutic dosage of 40 mg/day. During statin therapy, serum cholesterol was lowered by about 30%. Basal serum and urinary cortisol levels as well as serum cortisol response to ACTH were not influenced by statin therapy. Basal serum testosterone and its response to hCG were also unchanged by statin treatment. In addition, steroid hormone urinary metabolites were strikingly similar when patients were given HMG-CoA reductase inhibitors and when they were not. These results indicate that maximum therapeutic doses of statins have no negative impact on adrenocortical and testicular steroidogenesis even when these glands are maximally stimulated. PMID- 7883840 TI - Pharmacokinetics, pharmacodynamics, and tolerability of cabergoline, a prolactin lowering drug, after administration of increasing oral doses (0.5, 1.0, and 1.5 milligrams) in healthy male volunteers. AB - Cabergoline (CAB) a long-acting dopaminergic ergoline derivative, was given orally, in single doses of 0.5, 1.0, and 1.5 mg, to 12 healthy men in order to evaluate its PRL-lowering effect as well as its plasma pharmacokinetics and urinary excretion. Drug administrations were separated by 5-week washout periods. Blood samples for PRL and CAB determination were taken at baseline and for 840 h thereafter (every 1 h up to 4 h, every 4 h up to 12 h, every 24 h up to 168 h, and weekly up to 5 weeks). Fractional urine collections for CAB excretion were taken immediately before drug administration, every 4 h up to 12 h, and every 12 h up to 168 h. During the study period, blood pressure and heart rate were monitored at the same time periods of plasma sampling for CAB, and electrocardiographic tracings and hematological evaluations were performed before and after each treatment period. All CAB doses (0.5, 1.0, and 1.5 mg) produced in all subjects a complete PRL suppression (PRL < 1.0 micrograms/L), that occurred earlier and persisted longer with the two higher doses. PRL secretion areas [area under the curve (AUC) 0-48 h and 48-840 h] were higher after 0.5-mg than after 1.0- and 1.5-mg doses. In particular, in the first portion of the area, the difference between 0.5 mg and both 1.0 and 1.5 mg was highly statistically significant (P < 0.01) without significant differences between the two highest doses. Mean CAB maximal plasma concentrations (Cmax) were 33.3 +/- 3.69, 40.3 +/- 2.49, and 67.0 +/- 9.79 ng/L after 0.5, 1.0, and 1.5 mg CAB, respectively; time to Cmax was 2 h (median) for all doses; CAB AUC(0-168 h) after 0.5 mg CAB was significantly lower (P < 0.01) than after 1.5 mg CAB. The percentages of the administered doses of CAB excreted in urine were 1.1 +/- 0.1%, 1.1 +/- 0.1%, and 1.2 +/- 0.1% for the 0.5-, 1.0-, and 1.5 mg doses, respectively (P = NS). CAB AUCs(0-168 h) and Cmax normalized to the 1.0-mg dose were compared by two-way analysis of variance; no significant differences were found for CAB AUCs(0-168h); Cmax after 0.5 mg was significantly higher (P < 0.01) than after 1.0 and 1.5 mg CAB. A progressive decrease of systolic and diastolic blood pressure was observed, and symptomatic hypotension after the 1.0-mg dose did not allow one subject to receive the 1.5-mg dose. Other mild to moderate adverse events occurred only after 1.0 and 1.5 mg CAB. These results indicate that, in the dose range of 0.5-1.5 mg, the pharmacokinetics of CAB are dose independent, and that the pharmacodynamic data and the frequencies of adverse events of CAB are dose related, with no significant differences in the PRL-lowering effect of the 1.0- and 1.5-mg doses. PMID- 7883841 TI - High diagnostic sensitivity of glutamate decarboxylase autoantibodies in insulin dependent diabetes mellitus with clinical onset between age 20 and 40 years. The Belgian Diabetes Registry. AB - Patients with adult-onset Type 1 (insulin-dependent) diabetes mellitus (IDDM) are more difficult to identify than young patients, as their clinical onset is often less acute with a questionable state of insulin dependency. Classification may be facilitated by the detection of autoantibodies that are associated with IDDM. The prevalence of islet cell autoantibodies (ICA) and insulin autoantibodies (IAA) is, however, markedly lower in adult than in young patients. The present study assesses the usefulness of antibodies against glutamate decarboxylase (GAD), as a complementary marker. Sera from 312 recent-onset IDDM patients under age 40 and 163 age-matched controls were assayed for IAA, ICA, and antibodies against recombinant GAD65 (M(r) 65,000) or GAD67 (M(r) 67,000). IAA or ICA occurred in over 90% of patients diagnosed under age 20 but only in 65% of patients between age 20 and 40. Determination of GAD65-Ab did not increase the percent antibody positive patients under age 10, but did so at older ages: from 92-98% in the 10 19 years age group, and from 65-85% in the 20-39 years age group. The determination of GAD67-Ab did not add to the information provided by the GAD65-Ab assay. Our results indicate that, alone or in combination with ICA, the GAD65-Ab assay identified more patients with an IDDM marker in the age group 20-39 years than in the group under age 20. PMID- 7883842 TI - Multiphasic thyrotropin responses to thyroid hormone administration in man. AB - The magnitude and temporal pattern of serum TSH suppression after single or multiple doses of thyroid hormone (T3, T4, or triiodothyroacetic acid) were studied using third and fourth generation TSH assays (sensitivities, 0.01 and 0.001 mU/L, respectively). A constant T3 dose (263 micrograms i.v.) administered at a uniform clock time (1200 h) produced identical serum TSH suppression patterns, (percent of control TSH vs. hours) in euthyroid and hypothyroid subjects. The percent log TSH vs. log time plot revealed three temporally distinct linear suppression phases: phase 1, a rapid TSH suppression, onset 1 h and lasting for 10-20 h; phase 2, slower suppression, onset between 10 and 20 h and lasting for 6-8 weeks; and phase 3, an invariable low TSH level (< 0.01 mU/L) with chronic T3 suppression (100 micrograms four times a day). TSH escaped maximal suppression at a similar serum T3 level in both euthyroid and hypothyroid subjects (2.9 +/- 0.2 vs. 3.5 +/- 0.5 nmol/L, respectively; P > 0.9), despite different basal serum T3 values (2.0 +/- 0.1 vs. 0.6 +/- 0.1 nmol/L, respectively; P < 0.01). Two milligrams of triiodothyroacetic acid or 2 mg T4 given iv at 1200 h produced TSH suppression patterns similar to T3. The phase 1 suppression varied with the clock time of T3 administration, (steeper responses were seen at 2400 vs. 1200 h), whereas phase 2 responses were unaltered. This study shows that thyroid hormone suppression of TSH is a complex, biphasic, nonlinear process, which is reproducible and independent of thyroid status or the thyroid hormone analog used. It is hypothesized that phase 1 reflects inhibition of release of preformed hormone, whereas phase 2 likely reflects inhibition of de novo synthesis and/or thyrotroph storage of TSH. In contrast, phase 3 secretion seems to represent basal constitutive TSH release, which may have relevance to the role of thyroid hormone-suppressive therapy in the treatment of patients with benign or neoplastic thyroid disease. PMID- 7883843 TI - Prolonged opioid blockade does not influence luteinizing hormone modifications of the follicular and luteal menstrual phases. AB - Although an acute opioid withdrawal markedly modifies LH secretion in the different phases of the menstrual cycle, whether a sustained opioid blockade imbalances spontaneous LH modifications associated with the progression of the follicular or luteal menstrual phases is presently unknown. Accordingly, normal cycling women during either the follicular (n = 14) or luteal (n = 14) menstrual phase, randomly and in double blind fashion, received either placebo (n = 7 for each phase) or 50 mg/day of the oral opioid antagonist naltrexone (n = 7 for each phase). In each subject, LH pulsatility (10-min blood drawing for 8 h) and the pituitary LH response to a 10-micrograms GnRH stimulus were investigated at baseline and on the fifth day of placebo/naltrexone administration. In the follicular phase, after placebo treatment, the number and amplitude of LH pulses did not significantly vary, whereas mean LH levels (P < 0.01) and the LH response to GnRH (P < 0.05) were significantly increased. The same occurred after naltrexone treatment, when significant increases in both mean LH levels (P < 0.02) and LH response to GnRH (P < 0.025) were observed. In the luteal phase, after placebo administration, the frequency of LH pulses and mean LH levels were not modified, but both the amplitude of LH pulses (P < 0.025) and the LH response to GnRH were reduced (P < 0.02). The same occurred after naltrexone treatment, when significant decreases in both the amplitude of LH pulses (P < 0.05) and the LH response to GnRH (P < 0.05) were observed. During both phases of the menstrual cycle, the modifications observed during naltrexone treatment were similar and not significantly different from those observed during placebo. The present data do not support important modulatory functions for endogenous opioid peptides on spontaneous LH modifications occurring with the progression of the follicular or the luteal menstrual phases. PMID- 7883844 TI - Applications of an enzyme immunoassay for a new marker of bone resorption (CrossLaps): follow-up on hormone replacement therapy and osteoporosis risk assessment. AB - An enzyme-linked immunosorbent immunoassay (ELISA) for a new marker of bone resorption (CrossLaps) was evaluated. The ELISA procedure determines degradation products of type I collagen in urine. Values obtained in the ELISA and in pyridinoline by high pressure liquid chromatography were correlated after a correction for creatinine. A high correlation was found (r = 0.77; n = 81). A group of postmenopausal women (n = 180) showed an increase of more than 70% compared to values in premenopausal women (n = 104). Hydroxyproline was increased by 23%, osteocalcin by 52%, pyridinoline by 31%, and deoxypyridinoline by 50%. A highly significant decrease (60.7%) in the CrossLaps values was seen after 12 months in samples from patients receiving hormone replacement therapy compared to a placebo group. The spontaneous bone loss in an untreated group of women was determined by repeated forearm bone mass measurement over 24 months. Baseline values obtained in the CrossLaps ELISA were correlated to the rate of loss, yielding a highly significant r value of -0.61, indicating that CrossLaps might be a useful parameter for assessment of the risk of osteoporosis in postmenopausal women. PMID- 7883845 TI - No evidence for oncogenic mutations in the adrenocorticotropin receptor gene in human adrenocortical neoplasms. AB - The mechanism(s) of tumorigenesis for the majority of adrenocortical neoplasms remain unknown. G-Protein-coupled receptors were recently proposed as candidate protooncogenes. That activating mutations of this class of receptors might be important for tumor induction or progression of endocrine neoplasms was strengthened by the recent identification of such mutations in hyperfunctioning thyroid adenomas. To examine whether the ACTH receptor (ACTH-R) gene could be an oncogene in human adrenocortical tumors, we amplified by the polymerase chain reaction and directly sequenced the entire exon of the ACTH-R gene in 25 adrenocortical tumors (17 adenomas and 8 carcinomas) and 2 adrenocortical cancer cell lines. We found no missense point mutations or even silent polymorphisms in any of the tumors and cell lines studied. We conclude that activating mutations of the ACTH-R gene do not represent a frequent mechanism of human adrenocortical tumorigenesis. PMID- 7883846 TI - Heterogenous in vivo and in vitro expression of basic fibroblast growth factor by human pituitary adenomas. AB - Basic fibroblast growth factor (bFGF) is a potent mitogenic and angiogenic factor that is known to regulate GH, PRL, and TSH secretion. Sequences within a bFGF gene family member have been detected in transforming DNA samples derived from human PRL-secreting tumors. Furthermore, elevated serum concentrations of bFGF have been noted in patients with multiple endocrine neoplasia-1. To further examine the significance of bFGF in sporadic human pituitary adenomas, we investigated the expression of bFGF by these tumors. Using an enzyme-linked immunoassay that recognizes all 16-24 kilodalton molecular mass forms of bFGF, we measured circulating serum concentrations in 21 patients with sporadic pituitary adenomas; they ranged from less than 0.5-84 pg/mL and declined following surgical adenomectomy. To confirm the pituitary source of this growth factor, we determined in vitro bFGF release from 43 adenomas (10 GH, 7 PRL, 10 ACTH, 14 gonadotrope adenomas/oncocytomas, and 2 silent subtype 3 adenomas). bFGF was present with wide variability (0.75-2100 pg/24 h.10(5) cells) in conditioned culture media of all adenomas examined. The adenohypophysial source of this growth factor was further demonstrated by the reverse hemolytic plaque assay. Variable bFGF messenger RNA expression was identified by the reverse transcription polymerase chain reaction technique in 9 functional (2 PRL, 5 GH, 2 ACTH) and 7 nonfunctional (1 oncocytoma, 2 null cell, 2 gonadotrope, 2 Silent Subtype 3) adenomas examined. bFGF levels were unaltered in vitro following hypothalamic hormone stimulation/inhibition. The lack of a bFGF signal peptide sequence and hypothalamic hormone-independence suggest that secretion of this factor may be independent of pituitary hormone regulation. Immunocytochemistry failed to localize bFGF in tumors that released this factor in vitro, suggesting that storage of this peptide does not correlate with its synthesis and release. In conclusion, the heterogenous expression of bFGF suggests that it may play a specific and selective role in the tumorigenic process of some pituitary adenomas. PMID- 7883847 TI - Type 2 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal adrenal steroidogenesis. AB - Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) have been described which catalyze the interconversion of cortisol (F) to cortisone (E). 11 beta HSD activity has previously been reported in placenta and fetal membranes, where its role may be to protect the developing fetus from glucocorticoid excess. Furthermore, in the rat, an association between placental 11 beta HSD activity and the subsequent development of hypertension in the offspring has been reported. We have characterized the isoforms of 11 beta HSD in human fetal membranes and dissected placental tissue at term and investigated the relationship between placental 11 beta HSD activity and fetal and placental weights. 11 beta HSD activity studies in the presence of 0.1 mumol/L F and NAD (indicative of type 2 isoform activity) revealed high levels of activity in trophoblast dissected free of vessels (561 +/- 87 pmol E/h.mg protein; n = 4) > undissected placenta > cotyledenous vessels dissected away from trophoblast > placental and reflected amnion. In contrast, in the presence of 2.5 mumol/L F and NADP (indicative of type 1 isoform activity), only decidua and chorion demonstrated significant levels of 11 beta HSD activity. Type 1 11 beta HSD activity in chorion was probably due to decidual contamination, in that it was absent in decidua-free fused chorion obtained from a twin pregnancy. In keeping with these data, type 1 11 beta HSD messenger ribonucleic acid (1.5 kilobases) was detected in decidua, but in no other tissue, and high levels of type 2 11 beta HSD messenger ribonucleic acid (1.9 kilobases) were found in undissected placenta and trophoblast. In 27 term placentas, 11 beta HSD activity varied from 194-448 pmol E/h.mg protein. There was a weak, but significant, positive correlation between term placental 11 beta HSD activity and fetal weight (r = 0.408; P = 0.034), but no correlation with placental weight. Thus, in man, the reported association of a small fetus and a large placenta predisposing to adult hypertension cannot be explained on the basis of defective 11 beta HSD activity. However, the placenta offers an immense reservoir for F clearance (1.73-7.95 mumol/min.placenta) and may be a principal factor driving fetal ACTH secretion and, hence, fetal adrenal steroidogenesis. PMID- 7883848 TI - The effects of different doses of oral iodized oil on goiter size, urinary iodine, and thyroid-related hormones. AB - The prevention of iodine deficiency is still a worldwide concern. This study, conducted in Soja in western Sudan, was carried out to evaluate the effects of a dose of iodized oil sufficient enough to give maximum protection against goiter and provide an acceptable iodine supply without side-effects over a sufficiently long period of time. Adult goitrous subjects (n = 117) were randomly assigned to three groups, A, B, and C, and received a single oral dose of 200, 400, or 800 mg iodine, respectively. Urine and blood samples were collected at the start of the study and monitored for 1 yr. In the 3 groups, mean serum T4 and median urinary iodine and serum TSH values were restored to reference limits, and these were maintained for about 1 yr. In each treatment group, about two thirds of the subjects displayed a reduction in goiter size, and the 400- and 800-mg doses were not more efficient than the 200-mg dose to accomplish normalization of thyroid hormone values. A temporary rise in TSH was noted 1 week after iodine administration in 1, 3, and 10 subjects, respectively, and 1, 0, and 3 subjects showed biochemical signs of thyrotoxicosis during the year after treatment with the 3 different doses. The data indicate that oral administration of 200 mg iodine is effective and acceptable for treating iodine deficiency in adults for 1 yr. Because of the risks of side-effects and the shortage of medical resources, higher doses are not recommended. PMID- 7883849 TI - The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. AB - To study the effects of prolonged anorexia nervosa on bone density (BD) and to determine whether estrogen administration prevents bone loss in women with this disorder, 48 amenorrheic women with anorexia nervosa (mean age, 23.7 yr) were randomized to receive estrogen and progestin replacement (n = 22) or no replacement (n = 26). Clinical variables, biochemical indices, and spinal trabecular BD were measured every 6 months for a mean of 1.5 yr. Initial mean BD (130 +/- 27 mg K2HPO4/cm3, +/- 1 SD) was significantly (P < 0.001) less than normal (176 +/- 26 mg K2HPO4/cm3) and less than 2 SD below normal in 21 of the 48 women. Forty-four women completed the study (19 in the estrogen group and 25 in the control group). The mean duration of follow-up was comparable in the estrogen treated (1.57 +/- 0.89 yr) vs. the control group (1.41 +/- 0.69 yr). The estrogen treated group had no significant change in BD compared with the control group; however, there was a 4.0% increase in mean BD in patients with an initial ideal body weight of less than 70% who were treated with estrogen. In contrast, control patients with comparably low initial weight had a 20.1 % decrease in BD. Women in the control group with spontaneous resumption of menses, all of whom had an initial percent ideal body weight of greater than 70%, had a 19.3% increase in bone mass. It is concluded that: 1) estrogen replacement cannot prevent progressive osteopenia in young women with anorexia nervosa; 2) a subset of patients may have improved BD with estrogen and progestin administration depending on initial body weight; and 3) recovery from anorexia nervosa is associated with significantly improved BD. PMID- 7883850 TI - Identification of activins and follistatin proteins in human follicular fluid and placenta. AB - Follistatin, an activin-binding protein, is able to neutralize the various activities of activin by forming an inactive complex with it. The widespread tissue localization of follistatin is very similar to that of activin, which suggests that it plays a local modulatory role in the various paracrine/autocrine actions of activin. We detected significant activin-binding activities in human follicular fluid and placental homogenates, although they were much lower than those in porcine and bovine follicular fluids, which raised the possibility that follistatin is present in human follicular fluid and placenta. Therefore, we attempted to identify the protein molecules responsible for this activin-binding activity in human follicular fluid and placental homogenates. Human follicular fluid, collected from in vitro fertilization patients, was processed by affinity chromatography successive steps on sulfated gel matrices and reverse phase high performance liquid chromatography (HPLC). The final HPLC yielded abundant follistatin and almost equimolar amounts of activin-A, -AB, and -B. The follistatin protein showed characteristic multiple bands when analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The ability of each band to bind activin specifically was determined by activin binding assay and ligand blotting analysis. Several pieces of evidence, including the immunoblotting analysis and functional assay results, demonstrated the presence of three activin isoforms, A, AB, and B, in the follicular fluid. In contrast, human placental homogenates were found to contain follistatin and activin-A proteins only. Activin-AB and -B were not detected in any HPLC fraction, indicating that activin-A is the major form of activin in the human placenta. The present data indicate that the three activin isoforms and multiple forms of follistatin exist in human follicular fluid, and the activin-A isoform and follistatin exist in human placenta. They suggest that the physiological functions of the activin isoforms during embryonic development differ and that follistatin plays a functional role in the local control system(s) that regulates human reproduction. PMID- 7883852 TI - Intestinal lymphangiectasia in a patient with autoimmune polyglandular disease type I and steatorrhea. AB - Steatorrhea is seen in 18-24% of patients with autoimmune polyglandular disease (APD) type 1. The etiology and pathophysiology of the steatorrhea in this disease are unknown. We present a patient with APD type 1 and steatorrhea in whom biopsies revealed intestinal lymphangiectasia. This association has not been previously described. Intestinal lymphangiectasia may explain the steatorrhea in some patients with ADP type 1. As blind intestinal biopsies may miss areas of intestinal lymphangiectasia, endoscopically directed intestinal biopsies should be included in the evaluation of steatorrhea in APD type 1. PMID- 7883851 TI - Autoimmune endocrine disease induced by recombinant interferon-alpha therapy for chronic active type C hepatitis. AB - To elucidate the role played by interferon-alpha (IFN alpha) in the pathogenesis of autoimmune endocrine disease, we determined the autoantibody status, thyroid function test results, hemoglobin-A1c levels, and clinical symptoms of 58 patients who received IFN alpha for treatment of chronic active type C hepatitis. Each patient was treated for 6 months with a total dose of 391 +/- 140 x 10(6) U (mean +/- SD). Thyroid microsomal and/or thyroglobulin antibodies newly appeared or were increased in titer in 6 patients, 2 of whom developed hypothyroidism during IFN alpha therapy. Neither islet cell antibodies nor insulin-dependent diabetes mellitus developed during IFN alpha therapy, although hemoglobin-A1c levels were increased in 2 patients. One patient became positive for antimitochondrial antibodies, and another patient with preexisting antimitochondrial antibodies also manifested deterioration in liver function test results. Parietal cell antibodies and smooth muscle cell antibodies were the most frequent newly developed antibodies in 7 patients. Adrenal medullary cell antibodies and nuclear antibodies newly developed in 2 and 1 patients, respectively. At least 1 of 8 autoantibodies newly appeared in 19 patients (32.8%) and hypothyroidism developed in 2 patients (3.4%) during IFN alpha therapy. On the other hand, in 19 age- and sex-matched patients who did not receive IFN alpha, no autoantibody appeared, and no autoimmune disease developed during a follow-up period of 3 months. These findings suggest that IFN alpha acts as an immunomodulatory agent, inducing autoantibody production and the development of autoimmune disease in susceptible patients. Special attention should be paid to the development of hypothyroidism during IFN alpha therapy. PMID- 7883853 TI - Growth hormone inhibits lipoprotein lipase activity in human adipose tissue. AB - The in vitro effects of GH on human adipose tissue lipoprotein lipase (LPL) activity and messenger ribonucleic acid (mRNA) levels were studied using a tissue incubation technique. After preincubation for 3 days, abdominal sc adipose tissue pieces were exposed to cortisol (1000 nmol/L) for 3 days to induce LPL activity. Addition of GH (50 micrograms/L) to the cortisol-containing medium during the last 24 h (day 6) caused a decrease by 84 +/- 4% (P < 0.01) in heparin-releasable LPL activity and by 65 +/- 4% (P < 0.01) in total LPL activity. Moreover, the heparin-releasable fraction was reduced from 42% of the total LPL activity with cortisol alone to 17% when both GH and cortisol were present in the incubation medium during the last 24 h (P < 0.01). The reduction in LPL activity in response to GH was not accompanied by a decrease in the level of LPL mRNA measured by a solution hybridization ribonuclease protection assay. In adipose tissue incubated in the control medium for 6 days, the addition of GH alone during the last 24 h caused an insignificant decrease in heparin-releasable LPL activity. Low control activities limited the scope for further decrease. It is concluded that GH counteracts the potent stimulatory effect of glucocorticoids on LPL activity without affecting LPL mRNA levels. Therefore, the inhibition of LPL activity by GH probably occurs during translation and/or posttranslational processing of the enzyme, and the mechanism may involve a decreased channeling of the lipase to the cell surface. PMID- 7883854 TI - Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamopituitary disconnection: evidence that GHRP-6 main action is exerted at the hypothalamic level. AB - GH-releasing peptide (GHRP-6; His-D Trp-Ala-Trp-D Phe-Lys-NH2) is a synthetic compound that releases GH in a specific and dose-related manner through mechanisms and a point of action that are mostly unknown but different from those of GHRH. In man, GHRP-6 is more efficacious than GHRH, and a striking synergistic action on GH release is observed when GHRP-6 and GHRH are administered simultaneously. Based on such a synergistic action, it has been hypothesized that GHRP-6 acts through a double mechanism by actions exerted both at the pituitary and hypothalamic levels. The aim of the present study was 2-fold: 1) to further characterize the mechanism of action and synergistic effects of GHRP-6; and 2) to study its action in patients with hypothalamopituitary disconnection. Twelve patients with different neuroendocrine pathologies leading to a state of hypothalamopituitary disconnection (functional stalk section) and 11 age- and sex matched normal controls were studied. Each subject underwent 3 tests on separate occasions, being challenged with GHRH (100 micrograms, i.v.), GHRP-6 (90 micrograms, i.v.), or GHRH plus GHRP-6. GH was analyzed as the area under the curve (mean +/- SE, micrograms per L/120 min). In normal subjects GH secretion was 483.7 +/- 99.2 after GHRH, 1434.8 +/- 393.0 after GHRP-6, and 3771.5 +/- 399.6 after GHRH plus GHRP-6; the level of GH secreted after GHRH plus GHRP-6 treatment was significantly (P < 0.05) higher than after the arithmetic sum of GH levels after both compounds administered separately. In the group of patients with hypothalamopituitary disconnection, the level of GH secreted after GHRH was similar to that in controls (423.4 +/- 62.8); however, a complete blockade was observed after GHRP-6 (97.3 +/- 7.9), significantly (P < 0.05) lower than after GHRH as well as lower than the GHRP-6-induced GH release in control subjects (P < 0.01). After GHRH plus GHRP-6, the patients with hypothalamopituitary disconnection showed severely reduced secretion (745.3 +/- 67.6; P < 0.01 vs. controls), a value that was not significantly different from the arithmetic addition of levels produced by both compounds administered separately.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7883855 TI - Effect of endothelin-1 in man: impact on basal and adrenocorticotropin-stimulated concentrations of aldosterone. AB - The effect of exogenous endothelin-1 [2 pmol (5 ng)/kg.min for 15 min, followed by 1 pmol (2.5 ng)/kg.min for 105 min] on basal and ACTH (250 micrograms, i.v.) stimulated plasma concentrations of aldosterone, cortisol, testosterone, corticosterone, and 18-hydroxycorticosterone was investigated in a group of healthy male volunteers (n = 6). Plasma concentrations of aldosterone remained unchanged during a placebo experiment (i.e. in the absence of both exogenous ACTH and of endothelin-1). In the absence of exogenous ACTH, the i.v. administration of endothelin-1 did not influence plasma concentrations of aldosterone. The i.v. administration of 0.25 mg ACTH induced a rise in plasma concentrations of aldosterone from a basal value of 152.6 +/- 38.8 to 362.6 +/- 77.7 pmol/L. This ACTH-induced rise was markedly augmented (P < 0.01) by the concomitant administration of endothelin-1, when peak plasma concentrations of aldosterone of 632.5 +/- 230.2 pmol/L were observed. Basal and ACTH-stimulated concentrations of cortisol, corticosterone, and 18-hydroxycorticosterone were unchanged by the concomitant infusion of endothelin-1. Thus, exogenous endothelin-1 influences adrenal function in healthy men by selectively augmenting the ACTH-induced secretion of aldosterone. PMID- 7883856 TI - Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N terminally truncated peptide that is a major endogenous metabolite in vivo. AB - The metabolism of glucagon-like peptide-1 (GLP-1) has not been studied in detail, but it is known to be rapidly cleared from the circulation. Measurement by RIA is hampered by the fact that most antisera are side-viewing or C-terminally directed, and recognize both intact GLP-1 and biologically inactive. N-terminally truncated fragments. Using high pressure liquid chromatography in combination with RIAs, methodology allowing specific determination of both intact GLP-1 and its metabolites was developed. Human plasma was shown to degrade GLP-1-(7 36)amide, forming an N-terminally truncated peptide with a t1/2 of 20.4 +/- 1.4 min at 37 C (n = 6). This was unaffected by EDTA or aprotinin. Inhibitors of dipeptidyl peptidase-IV or low temperature (4 C) completely prevented formation of the metabolite, which was confirmed to be GLP-1-(9-36)amide by mass spectrometry and sequence analysis. High pressure liquid chromatography revealed the concentration of GLP-1-(9-36)amide to be 53.5 +/- 13.7% of the concentration of endogenous intact GLP-1 in the fasted state, which increased to 130.8 +/- 10.0% (P < 0.01; n = 6) 1 h postprandially. Metabolism at the C-terminus was not observed. This study suggests that dipeptidyl peptidase-IV is the primary mechanism for GLP-1 degradation in human plasma in vitro and may have a role in inactivating the peptide in vivo. PMID- 7883857 TI - Ontogeny of the estrogen receptor in the human fetal uterus. AB - The role of estrogen and its receptor in the development of the human fetal reproductive tract is unknown, but it may be involved in uterine maturation. In mouse and guinea pig uteri, studies have identified estrogen receptor (ER) protein during the fetal period. In the human, there are no published data regarding the ER during fetal uterine development. The purpose of this study was to investigate the pattern of ER gene and protein expression in the human fetal uterus. Uteri were obtained from abortuses (n = 43; range, 10-24 weeks gestation) of women undergoing elective termination of pregnancy. Reverse transcription polymerase chain reaction was performed with whole uteri as well as cultured fetal uterine stroma-like cells (n = 15). Immunolocalization studies were performed on frozen uterine sections using the H222 monoclonal antibody (Abbott Laboratories) directed against the ER (n = 20). Western blotting was used to confirm the identity of the ER protein (n = 3). Ligand binding studies were performed using radiolabeled [3H]estradiol (n = 5). Using reverse transcription polymerase chain reaction, a 263-basepair DNA fragment corresponding to the ER was consistently present in uteri after 15 weeks gestation. By immunohistochemistry, the ER is expressed within the uterine mesenchyme in a discrete cylindrical pattern at the interface of the differentiating endometrial stroma and myometrium. Western blotting confirmed the presence of a protein of an apparent mol wt of 66 kilodaltons, the predicted size of the ER. Ligand binding studies for the ER gave a value less than 8 fmol/mg protein. In summary, the ER gene is expressed in the uterus beginning in the early second trimester during fetal development. ER protein is localized in a discrete cylindrical pattern within the developing uterus. The highly specific location of the ER protein together with the messenger ribonucleic acid data suggest a role for the ER in differentiation of the primitive uterine mesenchyme into stromal and myometrial compartments. PMID- 7883858 TI - Expression and modulation of the parathyroid hormone (PTH)/PTH-related peptide receptor messenger ribonucleic acid in skin fibroblasts from patients with type Ib pseudohypoparathyroidism. AB - To explore the possibility that defects in the regulation of expression of the messenger ribonucleic acid (mRNA) coding for the PTH receptor could be involved in pseudohypoparathyroidism type Ib (PHP-Ib), PTH-induced cAMP production and PTH/PTH-related peptide (PTH-rp) receptor mRNA expression, measured using a ribonuclease protection assay, were compared in untreated and dexamethasone (dexa)-pretreated (5 x 10(-7) mol/L; 7 days) cultured skin fibroblasts from controls (n = 4) and patients with PHP-Ib (n = 6). In control fibroblasts, stimulation of cAMP production by PTH and expression of PTH/PTH-rp receptor mRNA were easily detectable and were not significantly affected by dexa pretreatment. In fibroblasts from three PHP-Ib patients demonstrating reduced PTH-induced cAMP production that was reversed by dexa, the level of basal PTH/PTH-rp receptor mRNA was also reduced, but increased to levels similar to those in control cells after dexa pretreatment. In fibroblasts from a patient with resistance to PTH not reversed by dexa, PTH/PTH-rp receptor mRNA expression was also significantly lower than that in control cells (18 +/- 13%; P < 0.001) and remained only 30 +/- 15% of that observed in control cells after dexa pretreatment (P < 0.001). In fibroblasts from two PHP-Ib patients expressing normal cAMP responsiveness to PTH before and after dexa treatment, the level of PTH/PTH-rp receptor mRNA was not different from that in control cells before or after dexa treatment. Thus, in all conditions where PTH-induced cAMP production by PHP-Ib fibroblasts was reduced, the abnormality could be explained by the reduced level of PTH/PTH-rp receptor mRNA in these cells. These results suggest that defects in the regulation of expression of the PTH/PTH-rp receptor mRNA, not structural defects in the receptor itself, explain the PTH resistance in PHP-Ib in the patients evaluated, but several different defects must exist. PMID- 7883859 TI - Soluble cytokine receptors and the low 3,5,3'-triiodothyronine syndrome in patients with nonthyroidal disease. AB - Cytokines have been implicated in the pathogenesis of the low T3 syndrome during illness. This is supported by our recent observation of a strong negative relationship between serum T3 and serum interleukin-6 (IL-6) in nonthyroidal illness (NTI). In the last few years, soluble cytokine receptors and cytokine receptor antagonists have been discovered in human serum. These proteins have the potential to further regulate cytokine activity. Therefore, we now studied the association between serum T3 and serum levels of soluble tumor necrosis factor alpha (sTNF alpha R p55 and sTNF alpha R p75), soluble interleukin-2 receptor (sIL-2R), and the interleukin-1 receptor antagonist (IL-1RA) in 100 consecutive hospital admissions with a wide variety of nonthyroidal diseases. Patients were divided into group A (T3, > or = 1.30 nmol/L; T4, > or = 75 nmol/L; n = 41), group B (T3, < 1.30 nmol/L; T4, > or = 75 nmol/L; n = 46), and group C (T3, < 1.30 nmol/L; T4, < 75 nmol/L; n = 13). Serum sTNF alpha R p55, sTNF alpha R p75, sIL-2R, and IL-1RA were lower in group A than in groups B and C [median values; sTNF alpha R p55, 1.25, 2.25, and 3.55 ng/mL (P < 0.001); sTNF alpha R p75, 2.02, 4.56, and 7.00 ng/mL (P < 0.001); sIL-2R, 184, 259, and 272 U/mL (P = 0.0004), respectively]. Serum IL-1RA levels were not different in the three groups (median values, 122, 193, and 258 pg/mL, respectively). Taking all patients together, a significant negative relation was found among serum T3 and sTNF alpha p55 (r = 0.59; P < 0.0001), sTNF alpha R p75 (r = -0.55; P < 0.0001), sIL-2R (r = -0.54; P < 0.0001), IL-1RA (r = -0.38; P = 0.001), and IL-6 (r = -0.56; P < 0.0001). A remarkable high correlation (r = -0.70; P < 0.0001) was found between serum T3 and a newly designed total score based on the summation of serum levels of IL-6 and the four soluble cytokine receptor proteins. IL-6 and the four cytokine receptor proteins were all significantly related to each other. Stepwise multiple regression indicated IL-6 and sTNF alpha R p75 as independent determinants of T3 [serum T3 = 2.09-0.32ln (sTNF alpha R p75) -0.15ln (IL-6); r = 0.70]. The variability in serum T3 was accounted for 35% by changes in ln (sTNF alpha R p75) and 14% by changes in ln (IL-6).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7883860 TI - Cytokine measurements and interpretation of cytokine assays in human disease. AB - Cytokines are powerful mediator and communication molecules capable of regulating a wide spectrum of biologic functions, including immune responses. Although the role of cytokines in the pathogenesis of human disease is not yet understood, assays for cytokines have become a common feature in research and clinical laboratories. However, numerous pitfalls accompany measurements of cytokine levels in body fluids and of cytokine synthesis or gene expression in tissue. Interpretation of results obtained in cytokine assays, especially those performed with pathologic specimens, is fraught with difficulties. While cytokine assays are clearly of value in monitoring patients treated with recombinant cytokines or receiving anticytokine therapy, the clinical significance of cytokine assays is not yet fully established. In this review, some of the complexities associated with cytokine monitoring are discussed. The crucial importance of understanding cytokine biology for meaningful assay interpretation is emphasized. PMID- 7883861 TI - Acute ethanol consumption synergizes with trauma to increase monocyte tumor necrosis factor alpha production late postinjury. AB - The hypothesis that acute ethanol uptake plus trauma can synergize to increase immunosuppression was tested. We found that, unlike non-alcohol-exposed patients, patients with acute alcohol use prior to trauma have a transient decrease in monocyte tumor necrosis factor alpha (TNF alpha) production during the very early postinjury (0-3 days) period. However, TNF alpha production by these alcohol exposed patients' monocytes (M0) became hyperelevated late postinjury (> 9 days). Consequently, these massively elevated M0 TNF alpha levels can contribute to posttrauma immunosuppression after acute alcohol use. We also demonstrate that normal monocyte activation with the superantigen, Staphylococcus enterotoxin B (SEB), results in a preferential induction of cell-associated M0 TNF alpha production, described as characteristic of immunosuppressed trauma patients. Acute in vitro ethanol treatment down-regulated the elevated TNF alpha production by trauma patients' M0 after either SEB, muramyl-dipeptide (MDP), interferon gamma plus MDP, or lipopolysaccharide (LPS) stimulation. Both SEB- and LPS induced TNF alpha mRNA induction was inhibited by acute alcohol treatment in normal M0, indicating that ethanol can regulate cytokine gene expression. An additional immunosuppressive effect of acute ethanol's stimulation was suggested by its induction of elevated transforming growth factor beta production in trauma patients' activated M0. PMID- 7883862 TI - Cystic fibrosis-related diabetes is associated with HLA DQB1 alleles encoding Asp 57- molecules. AB - The incidence of insulin-dependent diabetes in individuals with cystic fibrosis is nearly 100 times greater than in the general population. In the latter group, strong associations with specific HLA DQA1 and DQB1 alleles have been observed. To determine if a similar distribution of alleles occurs in cystic fibrosis patients with diabetes, a cohort of these individuals was typed for DQA1 and DQB1 alleles. HLA DQB1*0201 (Asp57-) was more frequent in diabetics compared to controls (40.4 vs 28%), while the frequency of alleles encoding Asp57+ molecules was lower in diabetics relative to both the cystic fibrosis-only controls (P = 0.025) and the general population (P = 0.008). The presence of at least one protective DQA1-DQB1 heterodimer (i.e., Arg52- and Asp57+, respectively) in cis or trans was significantly lower in the diabetics than in either of the control groups. Thus, the HLA alleles known to be associated with insulin-dependent diabetes mellitus in the general population are also found in diabetics with cystic fibrosis. PMID- 7883863 TI - A unique syndrome of immunodeficiency and autoimmunity associated with absent T cell CD2 expression. AB - CD2 is a glycoprotein expressed on the surface of human T cells that mediates adhesion between T cells and antigen presenting cells. CD2 also functions in concert with the T cell receptor to transduce signals that lead to T cell activation. The CD8 and CD4 molecules are transmembrane glycoproteins that are expressed on mutually exclusive populations of mature T cells and bind to determinants on major histocompatibility complex class I and class II molecules respectively. Like CD2, CD4 and CD8 function to promote adhesion between T cells and antigen presenting cells and potentiate signaling via the T cell receptor. We studied a patient with idiopathic lymphopenia and disseminated infection with Mycobacterium avium. The patient also suffered from recurrent deep venous thrombosis in association with anticardiolipin and anti-DNA antibodies. Peripheral blood T cells from this patient were polyclonal and expressed no detectable CD2 RNA or protein as determined by northern blotting, immunofluorescent staining with anti-CD2 antibodies, and failure to form rosettes with sheep red blood cells. In addition, the majority (85%) of this patient's T cells did not express either CD4 or CD8 but did express the alpha/beta T cell receptor. T cells from this patient failed to respond to stimulation with alloantigen or specific antigen. In contrast, there was a normal response to stimulation with immobilized anti-CD3 antibody. The clinical and immunologic findings in this patient provide in vivo evidence that the accessory molecules CD2, CD4, and CD8 play important roles in the regulation of normal human T cell activation. PMID- 7883864 TI - Factors influencing serum neopterin and beta 2-microglobulin levels in a healthy diverse population. AB - Sera and questionnaire data from a population-based random sample of healthy adults was used to evaluate factors influencing neopterin and beta 2 microglobulin (beta 2m) values. Both neopterin and beta 2m levels increased with age and were higher among white than blacks (mean values for whites and blacks: neopterin, 5.06 vs 4.49 nmol/L; beta 2m, 1.36 vs 1.28 mg/L). Gender differences were noted for beta 2m but not neopterin values (beta 2m males vs females: 1.37 vs 1.29 mg/L). Neopterin values were lower among current smokers than among nonsmokers (4.32 vs 5.16 nmol/L) and were higher among users of antihistamines (5.46 among users vs 4.65 nmol/L among nonusers). Neopterin and beta 2m were correlated in this healthy adult population (adjusted r = 0.53, P = 0.001), yet no other interrelationships with numerous biologic markers except between beta 2m and serum-soluble interleukin-2 receptor levels (adjusted r = .41, P = 0.05) were observed. These findings provide important baseline information to consider before planning or evaluating studies utilizing neopterin or beta 2m levels. PMID- 7883865 TI - Polyreactive IgM antibodies in the circulation are masked by antigen binding. AB - Human plasma containing IgM showed only minimal, if any, reactivity with a panel of antigens as measured by ELISA. In contrast, affinity-purified IgM showed many times more reactivity with the same panel of antigens. When plasma was added back to the affinity-purified IgM, the reactivity of the IgM with antigens was completely inhibited by undiluted plasma and by as much as 40% with as little as a 1:100 dilution of plasma. When the affinity-purified IgM was affinity-purified a second time by passage through antigen-specific columns (e.g., insulin or Fc or beta-galactosidase), the eluted antibodies bound not only to the antigen used for purification, but also to a panel of unrelated antigens, indicating that the antibodies were polyreactive. It is concluded that polyreactive IgM antibodies are present in the circulation but are masked by binding to circulating antigens. PMID- 7883866 TI - Increased interleukin-6 (IL-6) production in a young child with clinical and pathologic features of multicentric Castleman's disease. AB - A 21-month-old boy presented with a papular rash, lymphoadenopathy, and splenomegaly. He developed symmetric polyarthritis, fever, and progressive glomerulonephritis. Serologies for viral agents including HIV were negative. Antinuclear antibody was transiently positive, but no anti-DNA antibodies were present. CH50 and serum C3 values were low. Biopsies of skin, kidney, bone marrow, and lymph node were obtained. There was a perivascular and periadnexal lymphocytic infiltrate in the skin, with a normal epidermis. Renal biopsy showed proliferative mesangial glomerulonephritis. Bone marrow showed an increased number of plasma cells. Lymph node showed histologic changes described in multicentric Castleman's disease including marked follicular hyperplasia, vascular proliferation, and interfollicular expansion with numerous plasma cells. IL-6 mRNA was demonstrated in cells in the marginal zone and interfollicular regions of the node by in situ hybridization. Likewise, the serum IL-6 level was elevated during a clinical exacerbation of the patient's nephritis. These data suggest an underlying lymphoproliferative disorder, such as Castleman's disease, with overproduction of IL-6 resulting in systemic features of the disease, including glomerulonephritis. PMID- 7883867 TI - Expression of E-cadherin during craniofacial development. AB - The cell adhesion molecule E-cadherin is assumed to play an important role in organogenesis and histogenesis. We have analyzed the presence of E-cadherin during normal and disturbed craniofacial development with respect to palate and tooth formation by immunohistochemistry using a rat monoclonal antibody (DECMA-1) and by in situ hybridization using an oligonucleotide probe. Cleft palate was induced by retinoic acid (RA) treatment of pregnant dams. Normal and RA-treated fetuses of gestational days 14-18 were examined. E-cadherin was present in epithelia of both ectodermal and endodermal origin, including developing teeth and epithelia of the palate as well as respiratory and oral epithelia. The expression level of E-cadherin increased with age and differentiation. In normal fetuses, at day 18, the expression was higher in the epithelia of the oral cavity than in the forming nasal cavity. The expression pattern of E-cadherin implies that this molecule has a role during normal development of the epithelia of the craniofacial complex. PMID- 7883868 TI - Glucocorticoids, TGF-beta, and embryonic mouse salivary gland morphogenesis. AB - Branching morphogenesis is a fundamental embryologic process in many developing organs: salivary gland, lung, pancreas, mammary gland, and kidney. Glucocorticoids (CORT) are known to regulate morphogenesis in several branching organs (e.g., lung); we hypothesize that CORT is also important to embryonic mouse salivary gland morphogenesis. We studied the CORT-glucocorticoid receptor (GR) signal transduction pathway during embryonic mouse submandibular gland development. Western analysis demonstrates that the 96-kDa GR is present in E14 to E18 submandibular glands. The embryonic GR is functional, as defined by its ability to bind a DNA CORT response element, for all gestational ages evaluated (E14 to E18); increasing GR levels are observed with progressive development. The level of endogenous corticosterone in embryonic submandibular glands was also determined. Using radioimmunoassays corticosterone is first detected on day 15 of gestation; there is a progressive increase in steroid levels from day 15 to 18 of gestation. In addition, we investigated the effect of exogenous CORT on submandibular gland morphogenesis in vivo and in vitro. In vivo experiments were performed using maternal injection of CORT or sham injection on day 12 of gestation with sacrifice 72 hr post-injection (E15). CORT treatment significantly increases embryonic submandibular gland growth in vivo. To further analyze the effect of exogenous CORT on embryonic submandibular gland morphogenesis, E13 mouse submandibular glands were cultured under serum-free, chemically-defined conditions. A significant (P < 0.05) enhancement of mean branching ratios (72 hr/0 hr) is detected in CORT-supplemented explants (10(-5) M to 10(-8) M) compared to control explants; doses more dilute than 10(-8) M CORT do not significantly (P > 0.10) increase the induction of branching. In addition, CORT administration to embryonic mice in utero enhances the expression of acinar-cell specific mucin protein. These data indicate that the CORT-GR signal transduction pathway plays an important role in salivary gland morphogenesis. Northern analysis of TGF-beta 1, TGF-beta 2, and TGF-beta 3 transcript levels in vivo confirms the presence of TGF-beta 1 and TGF-beta 2 and identifies TGF-beta 3 in embryonic submandibular glands. To begin to identify a molecular mechanism of CORT-GR mediated submandibular gland morphodifferentiation, we studied the effect of CORT on growth factor gene expression, specifically TGF-beta. Northern analysis suggests that the CORT-GR signal transduction pathway modulates the rate of morphogenesis by regulating TGF-beta 2 and TGF-beta 3 mRNA expression. PMID- 7883869 TI - Holoprosencephaly and hypognathia with two proboscides: report of a case and review of unusual proboscides. AB - An unusual case of alobar holoprosencephaly is reported with hypognathic cyclopia and two proboscides, one supra- and one subocular. Only one previously reported instance with cyclopia and two proboscides is known. Four general types of proboscis formation are reviewed: holoprosencephalic, lateral nasal, accessory, and disruptive. PMID- 7883870 TI - Cranial base and vertebral column in human anencephalic fetuses. AB - The purpose of the present study was to investigate the axial skeleton related to the notochord in human anencephalic fetuses in order to elucidate the pathogenesis. Fifteen second trimester fetuses were examined. The spine and the cranial base were dissected and radiographed. Comparison with normal fetuses was performed. Two patterns of abnormal ossification were seen. Anencephalic cases without cervical rachischisis (Groups I and II) differed markedly from cases with cervical rachischisis (Group III). Morphological characteristics, such as bilateral narrowing of the basilar part of the occipital bone combined with normal cranio-caudal dimension, were found in cases without cervical rachischisis. In these cases frontal clefting of vertebral corpora occurred. Caudocranial shortening of the basilar part of the occipital bone was found in cases with cervical rachischisis, where complete median clefting of vertebral corpora also occurred. Because the vertebral corpora and the basilar part of the occipital bone develop around the notochord, which interacts also in the process of neurulation, the defects might indicate a notochordal insufficiency. The study showed that when the initial closure of the neural groove failed, the skeletal deviations were more extensive. The study supports the hypothesis that the notochord is an important clue to an understanding of the pathogenesis in anencephaly. PMID- 7883871 TI - Temporomandibular joint development in the marmoset--a mirror of man. AB - The timing of temporomandibular joint (TMJ) development in the cotton-eared marmoset was studied by histological examination of joints taken during embryogenesis and compared with TMJ development reported in man. Specimens were obtained via hysterotomy at intervals during pregnancies dated by estimation of uterine size or fetal head diameter. Elements of the marmoset TMJ were first identified at 70-85 days gestation, and TMJ morphogenesis was complete at 110-125 days. The chronological events of TMJ embryogenesis were found to run parallel to the human but were delayed by 30 days. At birth, after 150 days gestation, the marmoset TMJ resembled the human joint at the end of the second trimester, with all cell layers of the condylar cartilage in place and ossification started in temporal and condylar components. A new world primate, the cotton-eared marmoset is proposed as an animal model for craniofacial studies involving the TMJ on grounds of its close comparability to man. PMID- 7883872 TI - Prenatal sagittal growth of the osseous components of the human palate. AB - The human osseous palate consists of the palatine processes of the maxillary bone anterior to the transverse palatine suture and the horizontal processes of the palatine bone posterior to the suture. The purpose of the present study was to analyze the sagittal growth of these different bone components bordering the transverse palatine suture. The material comprised radiographs of cranial midsagittal tissue blocks from 44 human fetal specimens obtained by legally approved abortions. Gestational age (GA) ranged from 10 to 26 weeks and crown rump lengths (CRLs) from 50 to 240 mm. The lengths of the maxillary and palatine components of the hard palate were measured with a digital caliper on 3x-enlarged projections of the radiographs. A significant increase in the lengths of both palatal components occurred during the period investigated. Regression analysis on GA showed a linear course of the growth curve in the period studied and gave indirect evidence of a curvilinear shape in the period preceeding the one studied. Growth rates for the palatal dimensions were found to be proportional to that of CRL. The increase in total length resulted predominantly from an increase in the anteroposterior dimension of the maxillary component. PMID- 7883873 TI - Misidentification of clinical yeast isolates by using the updated Vitek Yeast Biochemical Card. AB - The Vitek Yeast Biochemical Card (YBC) is widely used as a rapid identification (RI) (within 48 h) system for clinical yeast isolates. We compared the RI results obtained by the YBC technique with matched results obtained with the API 20C system. The RI of germ tube-negative yeasts isolated from 222 clinical specimens was performed with the YBC system, and the results were compared with those of standard identifications obtained by using the API 20C system and morphology, with additional biochemical reactions performed as required. Commonly isolated yeasts (Candida albicans [n = 29], Candida tropicalis [n = 40], Torulopsis [Candida] glabrata [n = 28], Candida parapsilosis [n = 12], and Cryptococcus neoformans [n = 14]) were generally well identified (115 of 123 [93%] identified correctly, with only C. albicans, C. tropicalis, and C. neoformans mis- or unidentified more than once). The RI of less commonly isolated yeasts included in the YBC database, however, was less successful (54 of 99 [55%] correct). The YBC card failed to identify 42% (10 of 24) of Candida krusei isolates, 80% (4 of 5) of Candida lambica isolates, 88% (7 of 8) of Trichosporon beigelii isolates, and 83% (10 of 12) of Cryptococcus isolates (non-C. neoformans species). For most identification failures (79%; 42 of 53) there was no identification by the end of 48 h; the other identification failures (21%; 11 of 53) gave definite but incorrect identifications. Of eight rare clinical yeast isolates not included in the Vitek database, six were correctly, not identified, while two (25%) were falsely assigned a definite RI (one Hansenula fabianii isolate was identified as Rhodotorula glutinis, and one Hansenula isolate [non-Hansenula anomala] was identified as Hansenula anomala). While the Vitek YBC rapidly and adequately identifies common yeast isolates, it fails in the RI of more unusual organisms. PMID- 7883874 TI - Detection and sequencing of rotavirus VP7 gene from human materials (stools, sera, cerebrospinal fluids, and throat swabs) by reverse transcription and PCR. AB - Human rotavirus RNAs from stool samples, sera, cerebrospinal fluids, and throat swabs of 15 children with rotavirus gastroenteritis were detected and serotyped by reverse transcription and PCR. The reverse transcription-PCR method may allow us to consider rotavirus infections in other parts of the body in addition to the gastrointestinal tract. Moreover, sequence analysis of the VP7 gene was performed on seven samples (one stool, two serum, three cerebrospinal fluid, and 1 throat swab sample). There were no appreciable differences in viral sequences between samples from cerebrospinal fluids, sera, or stools. PMID- 7883875 TI - Early diagnosis of Lassa fever by reverse transcription-PCR. AB - We developed a method based on a coupled reverse transcription-PCR (RT-PCR) for the detection of Lassa virus using primers specific for regions of the S RNA segment which are well conserved between isolates from Sierra Leone, Liberia, and Nigeria. The specificity of the assay was confirmed by Southern blotting with a chemiluminescent probe. The assay was able to detect 1 to 10 copies of a plasmid or an RNA transcript containing the target sequence. There was complete concordance between RT-PCR and virus culture for the detection of Lassa virus in a set of 29 positive and 32 negative serum samples obtained on admission to the hospital from patients suspected of having Lassa fever in Sierra Leone. Specificity was confirmed by the failure of amplification of specific products from serum samples collected from 129 healthy blood donors in Sierra Leone or from tissue culture supernatants from cells infected with related arenaviruses (Mopeia, lymphocytic choriomeningitis, Tacaribe, and Pichinde viruses). Sequential serum samples from 29 hospitalized patients confirmed to have Lassa fever were tested by RT-PCR and for Lassa virus-specific antibodies by indirect immunofluorescence (IF). RT-PCR detected virus RNA in 79% of the patients at the time of admission, comparing favorably with IF, which detected antibodies in only 21% of the patients. Lassa virus RNA was detected by RT-PCR in all 29 patients by the third day of admission, whereas antibody was detectable by IF in only 52% of the patients. These results point to an important role for RT-PCR in the management of suspected cases of Lassa fever. PMID- 7883876 TI - Typing of Pneumocystis carinii strains that infect humans based on nucleotide sequence variations of internal transcribed spacers of rRNA genes. AB - Small portions of the 18S and the 26S rRNA genes, the entire 5.8S rRNA gene, and internal transcribed spacers ITS1 and ITS2 (located between the 18S and 5.8S rRNA genes and between the 5.8S and 26S rRNA genes, respectively) of Pneumocystis carinii that infect humans were cloned and sequenced. The nucleotide sequences of the 18S, 5.8S, and 26S rRNA genes determined in the study were approximately 90% homologous to those of P. carinii that infect rats, while the sequences of ITS1 and ITS2 of P. carinii from the two different hosts were only 60% homologous. The 18S, 5.8S, and 26S rRNA gene sequences of P. carinii from 15 patient specimens were determined and were found to be identical to each other, whereas the ITS sequences were found to be variable. With the observed sequence variation, it was possible to classify the ITS1 sequences into two types and the ITS2 sequences into three types. P. carinii strains that had the same type of ITS1 sequence could have a different type of ITS2 sequence. On the basis of the sequence types of the two ITS regions, P. carinii from the 15 patients were classified into four groups. P. carinii from three patient specimens were found to contain two different ITS sequence patterns. More surprisingly, one additional specimen was found to have one ITS sequence typical of P. carinii isolates that infect humans and another typical of P. carinii isolates that infect rats. The studies indicate that it is possible to type P. carinii strains on the basis from one patient, suggesting that coinfection with more than one strain of P. carinii may occur in the same patient. PMID- 7883877 TI - Efficient subtyping of pathogenic Yersinia enterocolitica strains by pulsed-field gel electrophoresis. AB - Yersinia enterocolitica is an enteropathogen that has recently and rapidly expanded over the world. There is a close correlation between the biotypes, serotypes, and phage types of the strains, making it virtually impossible to distinguish isolates of the same serotype with the classical phenotypic markers. In the present study, pulsed-field gel electrophoresis (PFGE) was used to compare the NotI genomic profile (i.e., pulsotype) of 20 strains each of serotypes O:3, O:9, and O:5. Eleven, 12, and 18 different pulsotypes were obtained, respectively, indicating that this technique is very efficient for subtyping pathogenic isolates of Y. enterocolitica. Within strains of serotype O:5, PFGE differentiated two subgroups that corresponded to two biotypes (biotypes 1A and 3). Comparison of the pulsotypes of three strains of biotype 3 and serotype O:3 (referred to as 3/O:3) with those of strains 4/O:3 and 3/O:5 suggested that the pulsotype is closer to the biotype than to the serotype. The pulsotypes of five pairs of strains isolated from the same patient or siblings were also analyzed. In four pairs, the two strains displayed identical pulsotypes, indicating that PFGE might be a powerful epidemiological tool. In the fifth pair, one restriction fragment differed, suggesting that genomic polymorphism may occur in vivo in Y. enterocolitica. Finally, the in vitro genomic stabilities of one strain each of Y. enterocolitica O:3, O:9, and O:5 were investigated. The pulsotypes of 10 isolated colonies were identical within each strain, indicating that in vitro, the genome of Y. enterocolitica is much more stable than that of Y. pestis. PMID- 7883878 TI - Genetic variability among Chlamydia trachomatis reference and clinical strains analyzed by pulsed-field gel electrophoresis. AB - Pulsed-field gel electrophoresis (PFGE) was applied to Chlamydia trachomatis reference strains representing each of the 18 serovars and to 29 clinical isolates from genital specimens collected in Bordeaux, France, or Malmo, Sweden. Comparison of the fingerprint patterns of the reference strains revealed a high level of polymorphism of the total DNA when SmaI was used (14 profiles), whereas the other enzymes, Sse8387I and ApaI, showed fewer differences. Some serovars, considered to be closely related on the basis of their antigenic determinants located on the major outer membrane protein (MOMP), such as D and Da or I and Ia, were shown to be different after PFGE of their genomic DNAs. However, serovars B and Ba and serovars L2 and L2a had identical patterns after analysis with the three endonucleases. When applied to clinical isolates, which were typed by restriction fragment length polymorphism analysis of the MOMP gene, PFGE allowed the detection of intragenotype polymorphisms and showed the identity of two strains successively isolated from the same patient. This technique seems to be an efficient tool for epidemiological studies when used in addition to serotyping or genotyping by restriction fragment length polymorphism analysis of the MOMP gene. PMID- 7883879 TI - Interactions with lectins and agglutination profiles of clinical, food, and environmental isolates of Listeria. AB - On the basis of preliminary trials with 14 collection strains of Listeria, five lectins (Canavalia ensiformis, concanavalin A; Griffonia simplicifolia lectin I; Helix pomatia agglutinin; Ricinus communis agglutinin; and Triticum vulgaris wheat germ agglutinin) were selected to set up a microtiter agglutination assay. The lectin agglutination profiles of 174 clinical, food, and environmental strains of Listeria monocytogenes, Listeria innocua, and Listeria seeligeri were investigated. Data on the standard determination of the antigenic structure were available for clinical strains; nonclinical isolates were assigned to serogroup 1 or 4 with commercial antisera. The listeria-lectin interaction was related to serological type rather than species; in particular, the strains assigned to serogroup 1 or belonging to serovars 1/2a, 1/2b, 1/2c, 3a, 3b, and 7 were never agglutinated by G. simplicifolia lectin I. The five-lectin set proved to be capable of detecting differences between serologically identical isolates of L. monocytogenes. Of the 150 isolates of this species, 144 were distributed over 15 different lectin agglutination profiles and 6 autoagglutinated, the overall typeability being 96%. However, the profiles encountered among L. monocytogenes isolates were not randomly distributed. With strains assigned to serogroup 1 or belonging to serovars 1/2a, 1/2b, 1/2c, and 3b, the clinical isolates fell into only two of the eight patterns recorded overall; with strains of serogroup 4 and serovar 4b, food and environmental isolates were distributed over eight of the nine patterns found in total, while clinical isolates were distributed over five patterns. In a comparative study of 15 epidemiologically relevant isolates of L. monocytogenes from five distinct outbreaks, strains with identical phage types and/or DNA fingerprints displayed identical lectin profiles. The heterogeneity of agglutination profiles may form the basis of a new approach to L. monocytogenes typing. PMID- 7883880 TI - Comparison of ribotyping and multilocus enzyme electrophoresis for subtyping of Listeria monocytogenes isolates. AB - Ribotyping was compared with multilocus enzyme electrophoresis (MEE) for subtyping 305 Listeria monocytogenes isolates from clinical and nonclinical sources. For ribotyping, EcoRI-restricted genomic DNA fragments of L. monocytogenes strains were separated by agarose gel electrophoresis, and Southern blots were probed with a cloned Escherichia coli rrnB operon (plasmid pKK3535) labeled with digoxigenin. The L. monocytogenes isolates were divided into 28 distinct ribotypes, while MEE analysis divided the same isolates into 78 electrophoretic types (ETs). On the basis of their ribotype profiles, the strains were divided into two subgroups. The ribotype alpha (RT alpha) subgroup contained serotypes 1/2a, 1/2c, and 3a, and the ribotype beta (RT beta) subgroup contained serotypes 1/2b, 3b, 4b, and 4ab. This division is in complete agreement with MEE analysis, which divides the species into two subgroups (ET groups A and B), with the same serotype distribution in each subgroup. Overall, MEE was more discriminating than ribotyping. However, in several instances ribotyping discriminated between isolates within the same ET. Ribotyping was more discriminating for serotypes 1/2a, 1/2c, and 3a (Simpson's Index for Diversity [DI] = 0.81) than for serotypes 1/2b and 4b (DI = 0.76). A substantial proportion (69%) of serotype 1/2b and 4b strains clustered in five ETs and five ribotypes. These data suggest that ribotyping and MEE do not provide adequate discrimination between strains of serotypes 1/2b and 4b. Methods such as pulsed-field gel electrophoresis and random amplified polymorphic DNA analysis should be explored for further discrimination of strains of these serotypes. PMID- 7883881 TI - Identification of mycobacteria by PCR-based sequence determination of the 32 kilodalton protein gene. AB - In this study, a part of the nucleotide sequence of the mycobacterial 32-kDa protein gene was determined by PCR-based sequencing. A total of 24 mycobacterial strains, representing 10 species, were studied. Sequences of all tested members of the Mycobacterium tuberculosis complex were identical to each other and to the previously published sequence of M. tuberculosis H37Rv. The sequences of M. avium and M. intracellulare were different from each other. MAIX strains, identified with the Gen-Probe MAIX test, had sequences identical to each other but clearly different from those of M. avium and M. intracellulare. Each of the other mycobacterial species investigated, i.e., M. kansasii, M. gastri, M. gordonae, and M. malmoense, had a unique species-specific sequence. These results demonstrate that there is variation in the nucleotide sequence of the 32-kDa protein gene among different mycobacterial species. Thus, we propose that this gene can be used for PCR-based identification of mycobacteria. PMID- 7883882 TI - Pneumococci in nasopharyngeal samples from Filipino children with acute respiratory infections. AB - The presence of Streptococcus pneumoniae in the upper respiratory tract was studied in 318 Filipino children less than 5 years old with an acute lower respiratory tract infection. Nasopharyngeal samples were obtained from 292 children. With both quantitative bacterial culture and detection of capsular polysaccharide antigens by coagglutination, counterimmunoelectrophoresis, and latex agglutination, pneumococci were found in 160 (70%) of the 227 samples eligible for analysis. Culture was positive in 115 samples and antigen was positive in 140 samples. The culture isolation rate was significantly lower if the patient had received antimicrobial agents in the 48 h prior to the sampling. The seven most common types or groups of pneumococci were 6, 14, 19, 23, 15, 7, and 11, which together accounted for 64% of all pneumococcal findings. PMID- 7883883 TI - PCR identification of four medically important Candida species by using a single primer pair. AB - A single pair of primers was used in a PCR assay to amplify and identify the DNAs from four medically important Candida species: C. albicans, C. parapsilosis, C. tropicalis, and C. (Torulopsis) glabrata. The report describes the first successful amplification of a chitin synthase-specific fragment from the four Candida species responsible for more than 90% of all cases of neonatal candidemia. The primer pair sequence was based on that from the C. albicans chitin synthase gene, CHS1 (J. Au-Young and P.W. Robbins, Mol. Microbiol. 4:197 207, 1990). Each of the four amplified products is a single band of a different size. The DNA sequence of each PCR product was determined, and four species specific probes were synthesized. The DNAs from as few as 10 organisms in 100 microliters of plasma could be detected after amplification and Southern blot analysis. In a retrospective study of 27 paired blood samples from 16 patients with culture-proven candidemia, PCR analysis was successful at detecting and correctly identifying to the species level 26 of the 27 Candida isolates. The speed and accuracy of this PCR-based technology make it a very powerful tool for detecting and diagnosing candidemia. Implementation of this assay for analyzing blood samples should result in the more timely treatment of neonatal candidemia, thereby reducing morbidity and mortality. PMID- 7883884 TI - Comparison of two panels of monoclonal antibodies for determination of Chlamydia trachomatis serovars. AB - A panel of monoclonal antibodies was developed for serovar typing of clinical isolates of Chlamydia trachomatis. The panel could distinguish all 15 established serovars from one another, although the hybridomas of the panel were developed by fusions of myeloma cells and spleen cells from mice immunized with antigen derived from the urogenital serovars D to L3. The typing assay was based on a dot enzyme immunoassay, and the monoclonal antibodies that were included in the panel reacted strongly in this assay. A collection of 289 clinical isolates from The Netherlands was typed. The observed serovar frequency distribution was 51 isolates of serovar D (17.6%), 103 isolates of serovar E (35.6%), 62 isolates of serovar F (21.5%), 28 isolates of serovar G (9.9%), 14 isolates of serovar H (4.8%), 2 isolates of serovar I' (0.7%), 20 isolates of serovar J (6.9%), and 9 isolates of serovar K (3.1%). These results were confirmed by typing these isolates with a panel of monoclonal antibodies purchased from the Washington Research Foundation, Seattle. No strain variation was observed within serovar D with both panels. However, restriction fragment length polymorphism analysis of the gene encoding the major outer membrane protein showed that 32 isolates were similar to the prototype D and 17 were similar to the variant D-. The two others showed a new restriction pattern. Our panel of monoclonal antibodies contained one monoclonal antibody that divided the serovar G isolates into two groups. This differentiation was confirmed by restriction fragment length polymorphism analysis, confining this difference to a known sequence variation in variable domain IV. These data support the subdivision of serovar G into serovars G (prototype strain UW-57) and Ga (prototype strain IOL-238). PMID- 7883885 TI - Molecular epidemiologic analysis of Vibrio cholerae O1 isolates by pulsed-field gel electrophoresis. AB - Isolates of Vibrio cholerae O1 El Tor from two well-defined cholera outbreaks in Malaysia were analyzed by using pulsed-field gel electrophoresis (PFGE). Isolates from sporadic cases occurring during the same time period were also studied. Digestion of chromosomal DNA from these isolates of V. cholerae O1 with restriction endonucleases NotI (5'-GCGGCCGC-3') and SfiI (5'-GGCCNNNN-3'), followed by PFGE, produced restriction endonuclease analysis (REA) patterns consisting of 13 to 24 bands (ranging in size from 46 to 398 kbp). Analysis of the REA patterns generated by PFGE after digestion with NotI and SfiI suggested the clonal nature and close genetic identity of the isolates obtained during each of the two outbreaks (Dice coefficient, 0.93 to 1.0). Although they had very similar REA patterns, the two outbreak clones were not identical. Isolates of V. cholerae O1 from sporadic cases, on the other hand, appeared to be much more heterogeneous (five different REA patterns detected in the five isolates tested; Dice coefficient, 0.31 to 0.81) than those obtained during the two outbreaks. We conclude that PFGE of V. cholerae O1 chromosomal DNA digested with infrequently cutting restriction endonucleases is a useful method for molecular typing of V. cholerae isolates for epidemiological purposes. PMID- 7883886 TI - Detection of Borrelia burgdorferi sensu lato in lesional skin of patients with erythema migrans and acrodermatitis chronica atrophicans by ospA-specific PCR. AB - The aim of this study was to develop a sensitive and specific PCR for the detection of Borrelia burgdorferi DNA. The plasmid-located gene coding for the outer surface protein A (OspA [31-kDa protein]) was used as a target. Nucleotide sequence information from different B. burgdorferi ospA genotypes was used to design primers homologous to different genotypes. The sensitivity of the nested PCR differed from 1 fg to 1 pg of borrelial DNA, depending on the strain analyzed. No cross-reactions with DNA from spirochetes other than B. burgdorferi or with human DNA were observed. A total of 22 skin biopsy samples from patients with erythema migrans (EM [n = 10]) or acrodermatitis chronica atrophicans (ACA [n = 12]) were examined for the presence of B. burgdorferi by nested PCR. Of 22 biopsies, 80% from EM patients and 92% from ACA patients were positive by PCR amplification. By comparison, 50% of the EM patients had elevated B. burgdorferi specific immunoglobulin M (IgM) and/or IgG antibody levels as tested by enzyme linked immunosorbent assay (ELISA) using purified B. burgdorferi flagella as antigen. A total of 33% of ACA patients had elevated IgM titers, and all had high IgG titers in their sera. Only 30% of specimens from patients with EM and none from patients with ACA were positive by culture. All culture-positive specimens were also positive by PCR. Thus, the sensitivities of the PCR were 80 and 92%, respectively, for patients with EM and ACA on the basis of the clinical and histopathological diagnoses of Lyme disease. From these results, we conclude that PCR is a suitable method to detect B. burdorferi sensu lato DNA in skin biopsy samples and could be applied as an additional diagnostic tool. PMID- 7883887 TI - Molecular fingerprinting of Legionella species by repetitive element PCR. AB - Repetitive element PCR (rep-PCR) uses outward-facing primers to amplify multiple segments of DNA located between conserved repeated sequences interspersed along the bacterial chromosome. Polymorphisms of rep-PCR amplification products can serve as strain-specific molecular fingerprints. Primers directed at the repetitive extragenic palindromic element were used to characterize isolates of Legionella pneumophila and other Legionella species. Substantial variation was seen among the rep-PCR fingerprints of different Legionella species and serogroups. More limited, but distinct, polymorphisms of the rep-PCR fingerprint were evident among epidemiologically unrelated isolates of L. pneumophila serogroup 1. Previously characterized Legionella isolates from nosocomial outbreaks were correctly clustered by this method. These results suggest the presence of repetitive extragenic palindromic-like elements within the genomes of members of the family Legionellaceae that can be used to discriminate between strains within a serogroup of L. pneumophila and between different Legionella species. rep-PCR appears to be a useful technique for the molecular fingerprinting of Legionella species. PMID- 7883888 TI - Use of Gen-Probe AccuProbes to identify Mycobacterium avium complex, Mycobacterium tuberculosis complex, Mycobacterium kansasii, and Mycobacterium gordonae directly from BACTEC TB broth cultures. AB - To evaluate the utility of Gen-Probe AccuProbes for the identification of mycobacteria directly from BACTEC TB 12B vials containing acid-fast bacilli, culture results for 11,375 clinical specimens other than blood received from 1 January 1992 to 30 September 1993 were reviewed retrospectively. During this period, a total of 359 of 11,375 BACTEC vials were positive for acid-fast bacilli and were evaluated for mycobacteria with one or more probes: 224 were probed for Mycobacterium tuberculosis complex, 253 were probed for Mycobacterium avium complex, 64 were probed for Mycobacterium kansasii, and 77 were probed for Mycobacterium gordonae. After initial testing with the probes, 75 vials were positive for M. tuberculosis complex, 99 were positive for M. avium complex, 11 were positive for M. kansasii, and 55 were positive for M. gordonae. Repeat testing of vials that were initially probe negative or testing of colonies from subcultures of these vials identified an additional 11 M. tuberculosis, 27 M. avium complex, 1 M. kansasii, and 9 M. gordonae that were not detected on initial screening. On the basis of these data, the percentage of organisms identified directly from the BACTEC TB 12B vials upon initial screening with each of the four AccuProbes was 87.2% for M. tuberculosis complex, 78.6% for M. avium complex, 91.7% for M. kansasii, and 85.9% for M. gordonae. PMID- 7883889 TI - Use of cephalexin-aztreonam-arabinose agar for selective isolation of Enterococcus faecium. AB - Cephalexin-aztreonam-arabinose agar (CAA), a new selective agar, was examined in comparison with nalidixic acid-colistin agar for the differentiation of Enterococcus faecium from other enterococci and the ability to isolate the organism from feces. Two hundred sixteen enterococcus isolates and a variety of gram-positive and gram-negative control strains were inoculated onto both media. All control strains of E. faecium were easily differentiated from Enterococcus faecalis and Enterococcus durans on the basis of arabinose fermentation on CAA. Differentiation of E. faecium from other enterococci or Streptococcus bovis was not possible on nalidixic acid-colistin agar. Increased isolation of E. faecium was demonstrated on CAA when both media were compared for the isolation of the organism from feces. CAA has been shown to possess excellent differential and selective features allowing the simple and effective isolation of E. faecium from heavily contaminated sites. PMID- 7883890 TI - Rapid identification of bacteria by PCR-single-strand conformation polymorphism. AB - A new molecular biological approach for the identification of bacteria is described. This approach employs PCR of bacterial cell lysates with conserved primers located in the 16S rRNA sequence flanking a variable region, and analysis of the amplified product was based on the principle of single-strand conformation polymorphism (SSCP). The PCR product was denatured and separated on a nondenaturing polyacrylamide gel. SSCP patterns were detected by silver staining the nucleic acids. The mobility of the single-stranded DNA is sequence dependent and could be used to identify the unknown bacteria. Feasibility of the technique was demonstrated for a broad panel of gram-negative and gram-positive bacteria. We tested over 100 strains of bacteria representing 15 genera and 40 species. With the use of only two primer sets, P11P-P13P and ER10-ER11, we were capable to discriminate the tested species at the genus and species levels. Species-specific patterns were obtained for, e.g., Clostridium spp., Listeria spp., Pseudomonas spp., and Enterobacter spp. PCR-SSCP is a sensitive technique; e.g., the sensitivity obtained for Escherichia coli cells was 30 CFU. This technique is a simple and rapid method for the detection and identification of a wide spectrum of bacteria by whole-cell-based PCR amplification with the use of conserved primers and identification by nondenaturing gel electrophoresis. PMID- 7883891 TI - Clinical significance of serum hepatitis C virus (HCV) RNA as marker of HCV infection. AB - We have evaluated the clinical significance of hepatitis C virus (HCV) RNA determination by analyzing a group of 221 hospitalized patients with abnormal liver function tests. Serum HCV RNA was detected by "nested" PCR amplification followed by nonisotopic hybridization. Of the 200 (90.5%) patients with anti-HCV positive enzyme-linked immunosorbent assay results, 152 (76%) were RIBA reactive, 47 (23.5%) had indeterminate results, and 1 (0.5%) was nonreactive. Of the 180 (90%) patients positive for anti-HCV and HCV RNA, 138 (76.7%) were RIBA reactive and 42 (23.3%) were RIBA indeterminate. The pattern of RIBA reactivity did not correlate with the presence of HCV RNA. Elevated alanine aminotransferase levels were associated neither with the presence of viremia nor with the RIBA pattern. Histological findings consistent with non-A non-B hepatitis correlated with the presence of HCV RNA but not with the RIBA pattern. HCV RNA was detected in 11 of 21 (52.4%) anti-HCV-negative patients. These 11 patients were either immunosuppressed or in the prodromic phase of acute hepatitis C. Circulating HCV RNA can therefore be described as being predictive of virus-induced liver damage in anti-HCV-positive patients and may be useful in the diagnosis of HCV infection in anti-HCV-negative immunosuppressed patients or in those with early acute infection. PMID- 7883892 TI - Laboratory investigation of a multistate food-borne outbreak of Escherichia coli O157:H7 by using pulsed-field gel electrophoresis and phage typing. AB - Two hundred thirty-three isolates of Escherichia coli O157:H7 were analyzed by both pulsed-field gel electrophoresis (PFGE) and bacteriophage typing. All 26 isolates from persons whose illness was associated with a recent multistate outbreak of E. coli O157:H7 infections linked to the consumption of undercooked hamburgers and all 27 isolates from incriminated lots of hamburger meat had the same phage type and the same PFGE pattern. Twenty-five of 74 E. coli O157:H7 isolates from Washington State and 10 of 27 isolates from other states obtained during the 6 months before the outbreak had the same phage type as the outbreak strain, but only 1 isolate had the same PFGE pattern. PFGE thus appeared to be a more sensitive method than bacteriophage typing for distinguishing outbreak and non-outbreak-related strains. The PFGE patterns of seven preoutbreak sporadic isolates and five sporadic isolates from the outbreak period differed from that of the outbreak strain by a single band, making it difficult to identify these isolates as outbreak or non-outbreak related. Phage typing and PFGE with additional enzymes were helpful in resolving this problem. While not as sensitive as PFGE, phage typing was helpful in interpreting PFGE data and could have been used as a simple, rapid screen to eliminate the need for performing PFGE on unrelated isolates. PMID- 7883893 TI - Restriction fragment length polymorphism Mycobacterium tuberculosis strains isolated from Greenland during 1992: evidence of tuberculosis transmission between Greenland and Denmark. AB - In order to describe the transmission of tuberculosis (TB) at the clonal level in a defined geographic region during a certain period of time, all isolates of Mycobacterium tuberculosis collected during 1992 from Greenland were subjected to analyses of DNA restriction fragment length polymorphism (RFLP). The RFLP patterns obtained by probing the genomic DNA with the repetitive insertion segment IS6110 revealed a high degree of similarity among the isolates, indicating a relatively high transmission rate and a close relationship between the individual M. tuberculosis clones. This was further confirmed by reprobing the Southern blots with two more-stable genetic markers, IS1081 and the DR sequence. The RFLP patterns were compared with those of 245 M. tuberculosis strains collected from Denmark during the same period (representing 91% of all new, bacteriologically verified cases of TB in Denmark in 1992). One of the three prevalent IS6110-defined clusters was traced to a group of immigrants from Greenland living in a small, defined geographical region in Denmark and to a group of Danish citizens either with known contact with these immigrants or, in other cases, with a record of previous travel or working activities in Greenland. The study showed that the present technique is extremely helpful in monitoring the spread of TB and thereby also contributing to improved disease control. PMID- 7883894 TI - Rapid identification of Candida albicans by using Albicans ID and fluoroplate agar plates. AB - Two commercially available agar media, Albicans ID and Fluoroplate, that use a chromogenic or a fluorogenic substrate for the detection and identification of Candida albicans were evaluated. From 1,006 clinical samples containing 723 yeast strains, 352 C. albicans strains were detected with either of the two media. The sensitivity of each of the two media was 93.8% and the specificity was 98.6%, with five false-positive reactions for Candida tropicalis and no false-negative reactions. PMID- 7883896 TI - Characterization of Coccidioides immitis isolates by restriction fragment length polymorphisms. AB - The marked increase in the number of cases of coccidioidomycosis in California in 1992 led to a study of isolates from various patients and environmental sources by restriction fragment length polymorphism (RFLP) analysis. Of 15 different isolates, most of the isolates (13 of 15) from California and 1 from Venezuela yielded one main RFLP pattern with evidence of two subgroups. The other two isolates (both from patients in the San Joaquin Valley of California) yielded a different RFLP pattern. PMID- 7883895 TI - Helicobacter sp. strain Mainz isolated from an AIDS patient with septic arthritis: case report and nonradioactive analysis of 16S rRNA sequence. AB - A campylobacter-like organism was isolated from an effusion of the left knee joint of an AIDS patient 2 weeks after bacteremia with a morphologically identical organism. Amplified genomic 16S rRNA sequences were analyzed by a nonradioactive blotting technique. The closest match was found with Helicobacter fenelliae (97.7% homology). Sequence data and phenotype suggest that the isolate may represent a so far unrecognized species of the genus Helicobacter. PMID- 7883897 TI - Propionibacterium acnes as a cause of aggressive aortic valve endocarditis and importance of tissue grinding: case report and review. AB - A case of prosthetic valve endocarditis with Propionibacterium acnes is described. The diagnosis was documented by histology and isolation of P. acnes from both blood and anulus tissue. Grinding of the tissue, which was first omitted to avoid contamination, was indispensable for cultivating the agent. The literature for P. acnes endocarditis is reviewed. PMID- 7883898 TI - Subtype analysis of hepatitis C virus in Indonesia on the basis of NS5b region sequences. AB - A recently identified subtype of hepatitis C virus, subtype 1d, was found to be common in Indonesia, being isolated from 4 (20%) of 20 and 11 (34%) of 32 patients with chronic hepatitis and liver cirrhosis, respectively. A new group of sequence variants was also identified, although its prevalence ratio was not as high in the area surveyed. PMID- 7883899 TI - Preliminary results of Pneumocystis carinii strain differentiation by using molecular biology. AB - The mode of Pneumocystis carinii transmission is controversial. Recent studies point to exogenous inoculation rather than reactivation, and person-to-person transmission has also been suggested. Comparison of nucleotide sequences of the large-subunit mitochondrial rRNA gene of P. carinii from human immunodeficiency virus-seropositive patients showed strain differences. PMID- 7883900 TI - Serological cross-reaction between Legionella spp. and Capnocytophaga ochracea by using latex agglutination test. AB - Cross-reactivity between Legionella spp. and Capnocytophaga ochracea was noted by latex agglutination tests (Serobact Legionella; Disposable Products, Adelaide, Australia). Four of 11 (36%) C. ochracea isolates agglutinated with latex reagents designed to identify Legionella pneumophila serogroups. C. ochracea isolated on buffered charcoal yeast extract media may give false-positive results in this Legionella latex agglutination assay. PMID- 7883901 TI - Antibiotic resistance of clinical isolates of Streptococcus pneumoniae in Greece. AB - The antibiotic susceptibilities of 1,002 Streptococcus pneumoniae clinical isolates from patients with community-acquired pneumonia were determined over an 18-month period. Resistance rates were 14% for penicillin, 20% for erythromycin, 26% for tetracycline, and 1% for chloramphenicol. Resistance to non-beta-lactam antibiotics was associated with penicillin resistance at statistically levels. PMID- 7883902 TI - Detection of immunoglobulin M (IgM), IgA, and IgG Norwalk virus-specific antibodies by indirect enzyme-linked immunosorbent assay with baculovirus expressed Norwalk virus capsid antigen in adult volunteers challenged with Norwalk virus. AB - Pre- and postexposure sera collected from 17 adult volunteers challenged with Norwalk virus as described previously (D. Y. Graham, X. Jiang, T. Tanaka, A. Opekun, P. Madore, and M. K. Estes, J. Infect. Dis. 170:34-43, 1994) were examined for Norwalk virus-specific immunoglobulin M (IgM), IgA, and IgG by indirect enzyme-linked immunosorbent assays with recombinant Norwalk virus antigen bound to the solid phase. Sixteen of the 17 volunteers had evidence of past infection, all presenting with preexisting IgG antibody of high avidity; only one volunteer had no evidence of previous infection. Virus infection was detected in 14 of the 16 volunteers with evidence of past infection, and 9 of the infected volunteers had symptomatic illness. A significant rise in both virus specific IgA and IgG titers was detected after challenge in all of the volunteers who became ill. Five of the asymptomatic volunteers who were infected had rising titers of virus-specific IgG, but only two of the five had a concomitant rise in their virus-specific IgA antibody titers. Antibody rises were detectable in eight of nine ill volunteers 8 to 11 days after challenge but in the asymptomatic volunteers only after more than 15 days had elapsed. Virus-specific IgM was detected after challenge in all 14 infected volunteers. Between symptomatic and asymptomatic volunteers there were no significant differences in titers of virus specific IgG and IgA in serum before challenge; however, there were significantly higher titers in symptomatic volunteers between 8 and > 90 days after challenge for virus-specific IgG and 8 and 24 days after challenge for virus-specific IgA. PMID- 7883903 TI - Optimization of quantitative culture assay for human immunodeficiency virus from plasma. Plasma Viremia Group Laboratories of the AIDS Clinical Trials Group (National Institute of Allergy and Infectious Diseases). AB - Experimental conditions essential to a simple, reproducible, quantitative human immunodeficiency virus plasma assay were determined. Five parameters were evaluated: length of culture, reproducibility, assay dilution schema, washing procedures, and anticoagulant usage. The recommended quantitative plasma assay utilizes undiluted citrated plasma cultured with peripheral blood mononuclear cells for 14 days with fivefold dilutions and a medium change on day 1 with no washing. PMID- 7883904 TI - Detection of mip gene by PCR for diagnosis of Legionnaires' disease. AB - The mip gene of Legionella pneumophila was demonstrated by PCR and probing in paired acute-phase and convalescent-phase sera from five patients with Legionnaires' disease but not in the acute-phase sera of 100 patients with pneumonia that showed no serological evidence of Legionella infection. PCR may help in cases presenting diagnostic difficulty. PMID- 7883905 TI - PCR amplification of variable sequence upstream of katG gene to subdivide strains of Mycobacterium tuberculosis complex. AB - PCR amplification of a species-specific 2-kb KpnI fragment of variable size located 10 kb upstream of the katG gene was used to subdivide 130 clinical isolates of Mycobacterium tuberculosis. Seven subtypes were identified, and their frequencies were distributed normally with respect to the size of the amplified product. PMID- 7883906 TI - Comparison of three stool-processing methods for detection of Salmonella serogroups B, C2, and D by PCR. AB - Three different stool sample-processing methods (centrifugation, immunomagnetic separation, and selective enrichment cultivation) for the identification of Salmonella serogroups by PCR were studied. The corresponding sensitivities in an ethidium bromide stained-agarose gel were 10(5), 10(3), and 10 bacteria, respectively. The PCR assay with overnight enrichment performed as well as, or even better than, the conventional culture technique. Of 485 clinical stool samples, PCR correctly identified all 230 culture-positive samples as well as mixed Salmonella infections in four cases. PMID- 7883907 TI - Transportation of Helicobacter pylori cultures by optimal systems. AB - Cultures of Helicobacter pylori on chocolate agar slants in bijou bottles and on chocolate agar plates inside BBL Campy Pouches were mailed from Dublin to Galway, Ireland; Bordeaux, France; and Beijing, China. Both systems maintained viability of H. pylori for at least 4 days under mailing conditions. Ninety percent of the isolates on the slants survived for 6 days, but only 30% of the isolates in the pouches survived. When the slants were stored at 4 degrees C after arrival, 50% of the isolates were recoverable 10 days after mailing. Failure of recovery was due to coccoid formation by the organisms. Contamination was not a problem in either system. Chocolate agar slants are considered the more suitable system for transporting H. pylori cultures, especially when transport time longer than 4 days is expected. PMID- 7883908 TI - Severe osteomyelitis due to the zygomycete Apophysomyces elegans. AB - We describe a previously healthy 69-year-old man presenting with osteomyelitis of the humerus due to the zygomycete Apophysomyces elegans. The infection was acquired in Aruba, The Netherlands Antilles. The skin provided the most likely portal of entry, although there was no history of a traumatic inoculation. The patient had no history of diabetes, and no underlying immune defects were found. Despite treatment with 7.9 g of amphotericin B, an interthoracoscapular amputation proved necessary to curtail the rapid spread of the fungus in this immunocompetent host. PMID- 7883909 TI - Evaluation of new transport medium for detection of herpes simplex virus by culture and direct enzyme-linked immunosorbent assay. AB - The transport medium Multi-Microbe Media (M4) was evaluated prospectively by culture and direct enzyme-linked immunosorbent assay (ELISA) for detection of herpes simplex virus from 473 specimens. In addition, 377 specimens in Bartels Viral Transport Medium were evaluated. By using culture as a "gold standard," the ELISA sensitivity was approximately 85%, while the specificities exceeded 96% for both media. PMID- 7883910 TI - Genomic stability of Legionella pneumophila isolates recovered from two cardiac transplant patients with nosocomial Legionnaires' disease. AB - Pulsed-field gel electrophoresis revealed that multiple consecutive isolates of Legionella pneumophila from two cardiac transplant patients remained genomically stable, despite exposure to host defenses and antimicrobial agents. PMID- 7883911 TI - Correlation between detection of herpes simplex virus in oral secretions by PCR and susceptibility to experimental UV radiation-induced herpes labialis. AB - We examined the oral secretions of 25 patients for herpes simplex virus (HSV) at the time of and following experimental UV radiation (UVR). HSV was detected in one or more oral secretion specimens in 5 of 12 (42%) cases by cell culture and in 8 of 12 (67%) cases by PCR. On the day of UVR, HSV was detected in 1 of 12 (8%) patients who developed a lip lesion and 2 of 16 (13%) patients who did not (the difference is not significant). We conclude that PCR is more sensitive than culture in the detection of HSV and that HSV is not shed with increased frequency from the oral cavity before the development of UVR-induced herpes labialis. PMID- 7883912 TI - Case of Aeromonas veronii (DNA group 10) bacteremia. AB - We describe the first case report of bacteremia due to Aeromonas veronii biotype veronii. The infection occurred in a 77-year-old man suffering from multiple underlying conditions which included cancer of the sigmoid colon. Because of the unusual biochemical phenotype of this group (ornithine decarboxylase positive), it was originally identified as Vibrio cholerae. PMID- 7883913 TI - Abortion associated with Campylobacter upsaliensis. AB - Campylobacter upsaliensis was isolated from the blood and fetoplacental material of an 18-week-pregnant woman who had contact with a household cat. We believe this is the first report of abortion associated with C. upsaliensis infection. PMID- 7883914 TI - Bordetella bronchiseptica in an AIDS patient cross-reacts with Legionella antisera. PMID- 7883915 TI - Femoral shaft fractures. PMID- 7883916 TI - Ultrasonography in developmental hip dysplasia. AB - With the evolving use of ultrasonography, there has been an increasing emphasis on the technically oriented diagnosis of developmental hip dysplasia. Graf's alpha and beta angles and Harcke's bony rim percentage are two of the more common criteria, but their repeatability and reliability have not been well documented. Fifty-eight hip ultrasounds of 29 infants were measured independently by three physicians, and statistical analysis was performed. It was concluded that Graf's and Harcke's methods could be repeatable with training and frequent use of ultrasonography. Harcke's guidelines have a large equivocal zone, which limited their clinical usefulness. Graf's angles gave a better classification, but their clinical relevance has not been proven. PMID- 7883917 TI - Brachyolmia: a report of two cases. AB - Brachyolmia is a rare form of skeletal dysplasia characterized by generalized platyspondyly without significant epiphyseal, metaphyseal, or diaphyseal changes in the long bones. Two cases of brachyolmia are reported: one of the Hobaek type, and another of the dominant type. One patient developed linear densities in the femoral necks: The manifestation is thought to be specific to the Hobaek type. Another patient had atlantoaxial instability and failure of ossification of the dens. These complications of brachyolmia have not been previously reported. PMID- 7883918 TI - Entrapment of pronator-quadratus in pediatric distal-radius fractures: recognition and treatment. PMID- 7883919 TI - Open-reduction and intertrochanteric osteotomy for osteonecrosis and extrusion of the femoral head in adolescents. AB - Extrusion of the femoral head during late childhood and adolescence can be caused by tissue interposition following traumatic hip dislocation, inflammatory joint disease, or avascular necrosis with flattening of the femoral head. We report our experience of treatment by reorientation of the extruded femoral head with combined open-reduction and intertrochanteric osteotomy in seven young patients with Ficat stage III or IV avascular necrosis. Six of the seven patients showed improvement of pain and limp. They also had radiographic improvement of joint space and congruency, which suggests that the degenerative process and further surgery may be delayed. PMID- 7883920 TI - Femoral head avascular necrosis associated with intramedullary nailing in an adolescent. AB - An adolescent developed avascular necrosis of the femoral head after intramedullary nailing for a femoral diaphyseal fracture. This complication is most likely secondary to injury to the posterior superior ascending branch of the medial circumflex artery at the time of rod insertion. This artery is situated close to the proximal insertion hole just posterior to the trochanteric notch and piriformis fossa. Other methods of fracture treatment, either operative or nonoperative, should be considered in skeletally immature patients. PMID- 7883921 TI - Avascular necrosis of the femoral head after closed intramedullary shortening in an adolescent. AB - Closed intramedullary shortening has become a popular treatment method for limb length inequality in adolescents. An important, potentially devastating complication of closed intramedullary fixation only recently described is avascular necrosis of the femoral head. We believe alternative treatment options must be considered to avoid this irreversible and catastrophic complication. A larger series may define the inherent risks of this complication and help determine the ideal treatment for femoral shortening and stabilization in the adolescent. PMID- 7883922 TI - The hammock suspension technique for hip spica cast application in children. AB - The hammock suspension technique for hip spica cast application in children utilizes a classic suspension system to support infants during application of the hip spica cast. The suspension system is simple and safe, and requires only readily available materials. The suspension system is exceptionally well tolerated by infants. This technique was used in nine infants with femur fractures. All fractures healed. This technique requires a minimum of skilled assistance and proved useful in children under 2 years of age. This technique is suggested as an extremely practical method of performing this common orthopaedic procedure. PMID- 7883923 TI - Longitudinal growth from the proximal femoral growth centers in the rabbit. AB - We selectively ablated the proximal growth centers of the femur in 3-week-old white New Zealand rabbits to study the contribution of each physis to bone length. The results were compared with the normal growth pattern determined in our previously published study. Growth in 10 femora with ablated greater trochanteric apophyses was normal as was the rate of growth for the 11 femora in which the proximal physis and femoral head were excised. Following femoral head excision, growth of 10 greater trochanteric apophyses, transferred in situ with muscular pedicle, was delayed initially, then increased at a rate very different from the control trochanteric growth. On the basis of this animal study, we support substitution of the greater trochanteric apophysis for an injured femoral neck physis to provide growth in the length of the femur. PMID- 7883924 TI - A prospective study of early spica casting outcomes in the treatment of femoral shaft fractures in children. AB - We analyzed the early spica casting outcomes of 50 children age 2 to 10 years with uncomplicated femoral shaft fractures treated at Johns Hopkins Hospital between October 1987 and October 1990. Our objective was to develop criteria for the prospective identification of patients who can be safely and dependably treated with early spica casting without excessive shortening of the fracture fragments. Forty-one (82%) children had an acceptable outcome and nine (18%) had an unacceptable outcome according to our definition of > 25 mm of fracture fragment overlap at 3 to 4 weeks follow-up. A new clinical test, the telescope test, was statistically significant (p < 0.001) for association with spica casting outcome. Age, sex, fracture location, mechanism of injury, fracture type, and resting roentgenogram fracture fragment overlap were not statistically significant (p > 0.10). The telescope test had a sensitivity of 78%, a specificity of 85%, and a negative predictive value of 95% for predicting spica casting outcome. The relative risk of failing spica casting after a positive telescope test was 20.4 (95% CI, 2.74-225.10). We conclude that children 2 to 10 years of age with uncomplicated femoral shaft fractures and a negative telescope test can be safely treated with early spica casting and have a 95% change of having a successful outcome with this treatment. PMID- 7883925 TI - Improved treatment of femoral shaft fractures in children utilizing the pontoon spica cast: a long-term follow-up. AB - This prospective study looked at 91 pediatric femur fractures. Patients were randomized into two groups: (a) A traditional group treated with 3 weeks in traction followed by spica; and (b) a pontoon spica group in which patients were treated first with only a few days in traction and then with a 90-90 pins-in plastic spica. The pontoon spica provides excellent short- and long-term results. These include (a) providing substantial cost savings; (b) causing much less inconvenience to the family and child; (c) reducing the number of inpatient days, thereby freeing hospital beds; (d) permitting early motion; (e) reducing the number of short-term complications; and (f) preventing excessive shortening while controlling rotation. PMID- 7883926 TI - The psychosocial characteristics of children with fractures. AB - We examined the psychosocial characteristics of 52 children with fractures. The parents completed questionnaires regarding injury circumstances, family functioning, home environment, and child behavior. Established psychosocial questionnaires were used: the McMaster Family Assessment Device (family environment), the Conners Parent Symptom Questionnaire, and Achenback Child Behavior Checklist (child behavior). Parent's perception of family functioning fell within the average range. The children exhibited a significantly high degree of social competence problems as well as behavioral difficulties. These behavioral difficulties included conduct disorder features, psychosomatic complaints, and impulsive/hyperactive behavior. To the extent that these variables constitute risk factors unique to children with fractures, prevention strategies can be designed to decrease the incidence of pediatric fractures. PMID- 7883927 TI - Neurovascular injury and displacement in type III supracondylar humerus fractures. AB - From July 1987 to January 1991, 59 consecutive type III supracondylar humerus fractures in children were identified at Children's Hospital, Boston. Twenty-nine patients (49%) had evidence of neurovascular compromise. The median nerve was involved in 15 (52%) of these patients and was associated with posterolateral displacement in 87% of cases. The radial nerve was involved in eight (28%) of these patients and was associated with posteromedial displacement in every case. Injuries to the brachial artery occurred in 11 (38%) of these patients and was associated with posterolateral displacement in 64% and posteromedial displacement in 36% of cases. We conclude that posterolateral displacement in type III supracondylar humerus fractures is strongly associated with median nerve injuries. Posteromedial displacement is responsible for injuries. Posteromedial displacement is responsible for injuries to the radial nerve in virtually every instance. Brachial artery injuries may occur with either type of displacement. Neurovascular injury is higher than previously reported in these fractures. PMID- 7883928 TI - A surgical technique of radioulnar osteoclasis to correct severe forearm rotation deformities. AB - Twenty-six forearms in 23 patients with marked pronation or supination deformities were treated with osteoclasis. Etiologies included 12 radioulnar synostoses, five brachial plexus injuries, three hemiplegias, two hemimelias, and four other types of deformities. Drill-assisted osteotomy of both the radius and ulna was followed 10 days later by manipulation to the desired functional position. Dominant extremities were placed in 20 degrees pronation, and nondominant extremities in 20 degrees supination. Range of motion was not significantly changed, but the arc of motion occurred in a more functional hand position. Average correction for 15 pronation deformities was 81 degrees and 69 degrees for 11 supination deformities. Two nonunions healed after bone grafting and there were no instances of neuromuscular compromise. Functional improvement was obtained in 25 of 26 forearms. PMID- 7883929 TI - Lessons learned after second-look arthroscopy in type III fractures of the tibial spine. AB - Ten patients with type III intercondylar eminence fractures with 6 years of follow-up underwent second-look arthroscopy after new injuries or complaints. Initial treatment was closed reduction (group I), arthroscopic reduction (group II), and arthroscopic reduction with internal fixation (group III). Lysholm ratings and one leg hop tests were normal in groups II and III and < 90% in group I. Tegner levels were 8, 9, and 10 in groups I, II, and III, respectively. International Knee Documentation Committee ratings were grades C, B, and A for groups I, II, and III, respectively. Arthroscopy revealed > 3 mm offset in groups I and II, suggesting loss of reduction, and grades II and III retropatellar chondromalacia. The fracture "footprint" is not congruous with the femoral condyle in extension or flexion. Loss of reduction led to laxity and prolonged morbidity. CLINICAL RELEVANCE: Loss of reduction is common after closed treatment of tibial spine fractures and should be closely monitored. Type III fractures that are unreducible or displaced require reduction, appropriate tensioning, internal fixation, and aggressive rehabilitation. PMID- 7883930 TI - Long-term follow-up of anterior tibial spine fractures in children. AB - In a long-term follow-up (mean 16 years) of 61 children with anterior tibial spine fractures, subjective knee function (Lysholm score) was excellent or good in 87% of the subjects and fair in 13%. Eleven percent of the children had a lower activity level (Tegner score) than desired. Muscle performance was affected in those subjects with the lowest Lysholm scores. Pathological knee laxity was found in 38% of the subjects, but was not reflected in poor subjective knee function. Age at injury did not influence the outcome. There was no indication that young children can eliminate slackness of the anterior cruciate ligament by further growth. Only in type III fractures was there a correlation between fracture displacement after healing and knee laxity, as well as between knee laxity and Lysholm score. Arthroscopy-guided or open reduction and internal fixation seems to be a worthwhile procedure only in dislocated type III fractures. PMID- 7883931 TI - Fracture of the superior pelvic quadrant in a child. AB - We present a case report (with review of the literature) of a 3-year-old child who was struck by an automobile, sustaining a superior quadrant pelvic fracture that involved the sacroiliac joint, the adjacent ilium, and the acetabulum. This was successfully treated by open reduction and fixation with cannulated screws. PMID- 7883932 TI - "Trapdoor" procedure for osteonecrosis with segmental collapse of the femoral head in teenagers. AB - Osteonecrosis of the femoral head in adolescents often leads to serious destructive changes in the hip with resulting significant disability. Between March 1981 and June 1990 we treated 13 teenagers (14 hips) using the "trapdoor" bone grafting procedure for severe femoral head osteonecrosis with articular surface collapse. Nine cases (10 hips) had the trapdoor procedure combined with containment osteotomy of the femur and acetabulum. Thirteen of the 14 hips had adequate follow-up to be included in this report. The main focus of this report is the 10 hips treated with a trapdoor bone grafting plus containment procedure (femoral osteotomy, acetabular osteotomy, or both). At an average follow-up of 4 years 5 months, clinically seven cases (eight hips) had a good result and two had a fair result. Radiographic evaluation showed six hips with a good result, three hips with a fair result, and one with a poor result. None of these 10 hips has yet required hip fusion or replacement arthroplasty, suggesting that trapdoor bone grafting plus containment can serve as a procedure to delay the need for hip fusion in femoral head avascular necrosis in teenagers. PMID- 7883933 TI - Analgesia for the reduction of fractures in children: a comparison of nitrous oxide with intramuscular sedation. AB - A prospective, randomized study was undertaken to compare the effectiveness of nitrous oxide with intramuscular sedation (meperidine and promethazine) in providing analgesia and amnesia during the reduction and treatment of children's fractures in an outpatient clinic setting. Fifteen patients received a 50:50 mixture of nitrous oxide and oxygen, and 15 received intramuscular injection. The two groups were similar in regard to gender distribution, age, and fracture types. Pain response was recorded using the Children's Hospital of Eastern Ontario (Canada) Pain Scale (CHEOPS) at the time of fracture reduction and 30 min postreduction. At the first follow-up visit a questionnaire regarding the patient's memory and subjective experience of the fracture reduction was answered. Data between the two groups were compared using the Mann-Whitney test. The CHEOPS scores, and the memory and subjective experience of the fracture reduction were similar between the two groups. Time in the outpatient department averaged 83 min for the intramuscular group and 30 min for the nitrous oxide group (p < 0.01). All of the nitrous oxide patients stated they would use nitrous oxide again, whereas only eight of 15 intramuscular patients stated they would try intramuscular sedation again. Nitrous oxide is as effective as intramuscular sedation in providing analgesia and amnesia in the treatment of children's fractures while having a more rapid onset and a shorter recovery period with greater patient acceptance. PMID- 7883934 TI - Major lower extremity lawn mower injuries in children. AB - Between 1983 and 1993, 16 children with 18 lower extremity power lawn mower related injuries were treated at Children's Hospital of Philadelphia. Eleven of 16 patients (69%) were bystanders or nonoperators. The average age at injury was 4 years 9 months. Length of follow-up averaged 3 years 10 months. There was an average of 4.9 procedures per patient. Fourteen of the 18 limbs injured required eventual amputation (78%). We propose a new classification of lawn mower injuries in children. The most common injury (16 of 18 limbs) was a shredding type injury and was either intercalary or distal. The second was a paucilaceration type (two of 18 limbs). Of the four salvaged limbs, there were two shredding type injuries, and on most recent follow-up are considered to have poor results. The two patients with the paucilaceration type injuries and limb salvage are considered to have excellent results. All patients with a shredding type injury ultimately required amputation or had poor results with the salvaged limb. Limb salvage surgery was associated with prolonged hospitalizations, a higher incidence of surgical problems, a longer treatment course, and more complications than early ablative procedures. PMID- 7883935 TI - Lawn mower injuries in children: a preventable impairment. AB - Every year there are seven million new lawn mowers purchased in the United States, each of which is capable of injuring young children, especially those > 14 years of age. A total of 33 children injured by a lawn mower were reviewed to identify the mechanism of injury, to determine the factors responsible for the accident, to determine an effective treatment regime, and to evaluate the permanent impairment for these patients. Classified according to their mechanism of injury, 14 children were injured as bystanders, 13 injured as riders, and six injured as operators. Categorized according to the anatomical location of injury, there were eight head and eye injuries, 12 upper extremity injuries, and 13 lower extremity injuries. There were 13 amputations (39.3%). The treatment management was satisfactory, but 23 children had an impairment > 40% of the whole person. We believe that the incidence of these injuries can be reduced by public awareness. Each orthopaedic surgeon should take on the task of educating the public about the dangers and wounding capacity of these machines and instructing the proper safety precautions that should be taken when mowing the lawn, especially when children are involved. The bottom line is that children should not be allowed in the yard while the lawn is being mowed nor should they be allowed to mow the lawn until they are > or = 15 years of age. PMID- 7883936 TI - Bone age determination in children with Legg-Calve-Perthes disease: a comparison of two methods. AB - In 100 children (17 girls, 83 boys) with Legg-Calve-Perthes disease, the average chronological age, pelvis bone age, and hand-wrist bone age were significantly different for the girls (8.2, 6.9, and 7.0 years, respectively; p < 0.05) and the boys (8.2, 7.4, and 5.9 years, respectively; p < 0.05). For the girls, the chronological age was greater than the pelvis bone age and the hand-wrist bone age (p < 0.05); there was no difference between the pelvis and hand-wrist bone age. For the boys, the chronological age was greater than the pelvis bone age and the hand-wrist bone age (p < 0.05); the pelvis bone age was greater than the hand wrist bone age and less than the chronological age (p < 0.05). The acromelic growth in Legg-Calve-Perthes disease may explain why the more proximal pelvis bone age in boys was less delayed than that of the more distal hand-wrist. PMID- 7883937 TI - Progressive coxa valga after childhood excision of the hip abductor muscles. AB - To our knowledge, progressive coxa valga, femoral anteversion, and hip subluxation after surgical resection of soft tissue tumors of the gluteal muscles have not been described. The importance of this paper is to document proximal femoral deformity and hip subluxation in children after tumor resection of the hip abductor muscles, to provide guidelines for diagnosis and management of this problem, and to avoid late complications of progressive joint incongruity. Late deformity was seen in two cases after limb salvage surgery for a soft tissue buttock tumor. In both cases, the gluteus medius and minimus muscles were completely resected and the tensor fascia lata and gluteus maximus were partially resected. The ages of the patients at initial treatment were 4 months old and 5 years old, and both patients were followed for a minimum of 4 years. Valgus deformity was seen as early as 15 months. One patient has had a varus osteotomy to correct severe coxa valga and hip subluxation; the other patient with moderate deformity is being followed clinically and radiographically. PMID- 7883938 TI - Capsulorrhaphy versus capsulectomy in open reduction of the hip for developmental dysplasia. AB - Capsulorrhaphy and capsulectomy were prospectively compared in open reduction of the hip for developmental dysplasia. There were 39 patients: 16 capsulorrhaphy and 23 capsulectomy. Follow-up averaged 22 months postsurgery. The surgical technique included innominate osteotomy, and femoral shortening and derotation. Avascular necrosis developed in one capsulorrhaphy patient. Postoperative redislocation occurred in three capsulorrhaphy and no capsulectomy patients. Three capsulorrhaphy and three capsulectomy patients had acetabular dysplasia. Neither capsulorrhaphy nor capsulectomy produced superior hip motion at last examination. PMID- 7883939 TI - The depoliticizing of hunger. PMID- 7883940 TI - Food protection: the mission may be hazardous to your health. PMID- 7883941 TI - Public health and health care reform: the American Public Health Association's perspective. AB - This paper discusses the American Public Health Association's goals with regards to the current health care reform debate. By outlining the organization's historical context with regards to health care reform as well as the parameters of the current medical care and public health crises, the paper explains why APHA's advocacy efforts focused on two major issues: the adoption of a national health program that features universal coverage with a comprehensive set of benefits for all our nation's residents, and the enhancement of the federal, state, and local public health infrastructure. The paper argues that both medical care services and public health programs must be expanded if we are to improve the nation's overall health status. PMID- 7883942 TI - Global environmental change and human health: new challenges to scientist and policy-maker. AB - Human health may not remain sustainable if damage to the global environment continues. The argument is simple: Earth is essentially a closed system; humans are proliferating and commandeering more surface area, food and energy; the resultant accumulation of waste gases, depletion of soil and water, and loss of biodiversity is starting to overload Earth's carrying capacity. There are limits in any closed system and our species is now pressing against some of them. These are new problems and we cannot be certain of the consequences for human health. A warmer world will probably have more frequent heatwaves, unstable weather, increased spread of mosquito-borne infectious diseases, and disruptions to agriculture. Ozone depletion, if sustained, may cause moderate increases in skin cancer and cataracts, and may damage crop growth and marine stocks. Depletion of agricultural resources, overfishing, and loss of genetic resources from species extinction all entail potentially serious consequences for human health. The manifest uncertainties of these global change processes and the need for prediction, rather than empirical observation, create new challenges to health scientists. Likewise, policy-makers will have to deal with best estimates and long time-frames, informed by understanding of ecological realities. PMID- 7883943 TI - Media advocacy: a strategy for empowering people and communities. AB - Media advocacy is a new strategy that is emerging in the public health community. It has been particularly visible in communities of color. Media advocacy is defined as the strategic use of mass media to advance public policy initiatives. Media advocacy is rooted in community advocacy and has as its goal the promotion of healthy public policies. It can be differentiated from traditional mass media strategies in a number of ways. Media advocacy shifts the focus from the personal to the social, from the individual to the political, from the behavior or practice to the policy or environment. While traditional media approaches try to fill the "knowledge gap," media advocacy addresses the "power gap." Improvements in health status are believed to come about primarily from gaining more power over the policy environment rather than simply gaining more knowledge about health behaviors. PMID- 7883944 TI - Highway deaths: false PR on the effects of PR. AB - In June, 1988, the Department of Public Safety (DPS) in South Carolina launched a media campaign, called "Highways or Dieways?", in an attempt to reduce motor vehicle fatalities. Deaths per vehicle mile declined during the succeeding years and the DPS attributed all of the reduction to the campaign, gleaning some 62 awards in the process. This research indicates that the DPS took credit for a decline in fatalities that resulted from other factors. Fatality rates in South Carolina were actually higher during the campaign than would have been expected from the historic association of South Carolina's rates with the national rate or those of other states in the region. The campaign actually illustrates the principle that ad campaigns alone are often ineffective in changing public health. PMID- 7883945 TI - Knowledge of risk factors and risk behaviors related to coronary heart disease among blue and white collar males. AB - In this report the data regarding coronary heart disease (CHD) from the 1990 Health Promotion and Disease Prevention Supplement of the National Health Interview Survey are used to examine the relationship between risk factor knowledge and health related behaviors among currently employed white collar (N = 5,349) and blue collar (N = 4,158) men workers. Blue collar employees have less knowledge about CHD risk factors, less favorable risk factors status, and poorer health practices than their white collar workers. Despite these findings within each occupational group, the relationship of knowledge to either risk factor status or health practices is similar. Knowledge is generally related to the attempts to change behaviors. However, for the different risk factors, the associations vary. For example, knowledge of cigarette smoking as a risk factor of CHD is negatively associated with reported ever smoking or current smoking, but not with heavy smoking. In contrast, knowledge of overweight, high serum cholesterol, and high blood pressure as CHD risk factors is not associated with risk factor status. These results suggest that while difference in level of knowledge and risk profiles remain between blue collar and white collar employees, the associations between knowledge and risk profiles are similar. Programs located at worksites must continue to provide education opportunities about the risk factors, especially among blue collar workers. PMID- 7883946 TI - AIDS knowledge, occupational precautions, and public education activities among law enforcement officers and first responders. AB - A survey on AIDS was administered within a large, southern California jurisdiction to law enforcement officers and first responders (paramedics, firefighters). Respondents had accurate knowledge about AIDS but several incorrect perceptions about HIV transmission; a substantial proportion believed that HIV could be contracted from casual contact. AIDS training was not frequent. Self-assessment of HIV risk was medium to high risk in one-third of respondents, and was largely attributable to fear of occupational exposure. Appropriate precautionary professional practices were adopted at low frequencies, with respondents adopting preventive measures less than 50% of the time on 7 of 10 measures. Seventeen percent reportedly received requests for HIV/AIDS education from members of the public, which is incongruous with law enforcement officers' and first responders' demonstrated level of knowledge about HIV transmission. It was concluded that improved educational programs on HIV/AIDS are needed for law enforcement officers and first responders to increase the use of occupational precautions in the field, and to improve the accuracy of public AIDS education activities conducted by these professionals. PMID- 7883947 TI - Molecular and cellular basis of deficiency of the b subunit for factor XIII secondary to a Cys430-Phe mutation in the seventh Sushi domain. AB - We studied the defect responsible for deficiency of the b subunit for factor XIII in the first known case of this condition. The patient is a compound heterozygote of two genetic defects: deletion of A-4161 at the acceptor splice junction of intron A, resulting in a loss of the obligatory AG splicing sequence; and, replacement of G-11499 by T in exon VIII, resulting in an amino acid substitution of Cys430 by Phe. To determine how the latter mutation impaired b subunit synthesis, recombinant b subunit bearing the mutation was expressed in BHK cells. The mutant as well as wild-type b subunit was synthesized by the cells. However, the apparent molecular weight of the mutant was slightly higher than those of the wild-type and plasma b subunits under nonreducing conditions, probably because of destruction of a disulfide bond. The mutant b subunit was secreted from the cells much less effectively than the wild type and remained susceptible to endoglycosidase H, indicating that it was not transported from the endoplasmic reticulum to the Golgi apparatus where the processing of oligosaccharides occurs. Immunofluorescence study suggested that the mutant protein was retained in the endoplasmic reticulum. These studies demonstrate that a Cys430-Phe mutation does not prevent the de novo synthesis of the b subunit, but alters the conformation of the mutant protein sufficiently to impair its intracellular transport, resulting in its deficiency in this patient. PMID- 7883949 TI - Effect of alpha-tocopherol on restenosis after angioplasty in a model of experimental atherosclerosis. AB - The ability of alpha-tocopherol to reduce restenosis after angioplasty was tested in a rabbit model in which angioplasty was performed on established atherosclerotic lesions. Lesions induced by 4 wk of cholesterol feeding after focal desiccation of femoral arteries were balloon dilated. 3 wk after angioplasty, angiographically determined minimum luminal diameters were less in the untreated group (0.80 +/- 0.51 mm) than in the group treated with oral alpha tocopherol beginning 19 d before angioplasty (1.38 +/- 0.29 mm; P < 0.01). The cross-sectional area of the intima-media was greater in the untreated group (1.18 +/- 0.48 mm2) than in the alpha-tocopherol group (0.62 +/- 0.25 mm2, P < 0.0001). These differences were not due to vasoconstriction or altered plasma cholesterol. Alpha-tocopherol thus reduced restenosis after angioplasty in this model. In rabbit vascular smooth muscle cells, oxidized low density lipoprotein stimulated DNA synthesis. Alpha-tocopherol treatment inhibited DNA synthesis stimulated by oxidized low density lipoprotein, but not by serum. The findings are consistent with the hypothesis that oxidized lipids can stimulate hyperplasia and that antioxidants may limit hyperplasia by inhibiting either the oxidation or the proliferative effects of oxidants on cells. PMID- 7883948 TI - Modulation of neutrophil influx in glomerulonephritis in the rat with anti macrophage inflammatory protein-2 (MIP-2) antibody. AB - The role of the chemokine, macrophage inflammatory protein-2 (MIP-2), during anti glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was studied. Rat MIP-2 cDNA had been cloned previously. Recombinant rat MIP-2 (rMIP 2) from Escherichia coli exhibited neutrophil chemotactic activity and produced neutrophil influx when injected into the rat bladder wall. By using a riboprobe derived from the cDNA and an anti-rMIP-2 polyclonal Ab, MIP-2 was found to be induced in glomeruli with anti-GBM Ab GN as mRNA by 30 min and protein by 4 h, with both disappearing by 24 h. The expression of MIP-2 correlated with glomerular neutrophil influx. A single dose of the anti-MIP-2 Ab 30 min before anti-GBM Ab was effective in reducing neutrophil influx (40% at 4 h, P < 0.01) and periodic acid-Schiff deposits containing fibrin (54% at 24 h, P < 0.01). The anti-rMIP-2 Ab had no effect on anti-GBM Ab binding (paired-label isotope study). Functional improvement in the glomerular damage was evidenced by a reduction of abnormal proteinuria (P < 0.05). These results suggest that MIP-2 is a major neutrophil chemoattractant contributing to influx of neutrophils in Ab-induced glomerular inflammation in the rat. PMID- 7883950 TI - The low molecular mass GTP-binding protein Rho is affected by toxin A from Clostridium difficile. AB - Enterotoxin A is one of the major virulence factors of Clostridium difficile, and the causative agent of antibiotic-associated pseudomembranous colitis. In cell culture (NIH-3T3, rat basophilic leukemia cells) toxin A inhibits Clostridium botulinum ADP-ribosyltransferase C3 (C3)-catalyzed ADP-ribosylation of the low molecular mass GTP-binding Rho proteins. Rho participates in the regulation of the microfilament cytoskeleton. Decrease in ADP-ribosylation of Rho occurs in a time- and concentration-dependent manner and precedes the toxin A-induced destruction of the actin cytoskeleton. Action of toxin A is not due to proteolytical degradation of Rho or to an inherent ADP-ribosyltransferase activity of toxin A. Toxin A-induced decrease in ADP-ribosylation is observed also in cell lysates and with recombinant RhoA protein. A heat stable low molecular mass cytosolic factor is essential for the toxin effect on Rho. Thus, the enterotoxin (toxin A) resembles the effects of the C. difficile cytotoxin (toxin B) on Rho proteins (Just, I., G. Fritz, K. Aktories, M. Giry, M. R. Popoff, P. Boquet, S. Hegenbath, and C. Von Eichel-Streiber. 1994. J. Biol. Chem. 269:10706-10712). The data indicate that despite different in vivo effects, toxin A and toxin B act on the same cellular target protein Rho to elicit their toxic effects. PMID- 7883951 TI - Increased secretory demand rather than a defect in the proinsulin conversion mechanism causes hyperproinsulinemia in a glucose-infusion rat model of non insulin-dependent diabetes mellitus. AB - Hyperproinsulinemia in non-insulin-dependent diabetes mellitus (NIDDM) is due to an increased release of proinsulin from pancreatic beta cells. This could reside in increased secretory demand placed on the beta cell by hyperglycemia or in the proinsulin conversion mechanism. In this study, biosynthesis of the proinsulin conversion enzymes (PC2, PC3, and carboxypeptidase-H [CP-H]) and proinsulin, were examined in islets isolated from 48-h infused rats with 50% (wt/vol) glucose (hyperglycemic, hyperinsulinemic, and increased pancreatic proinsulin to insulin ratio), 20% (wt/vol) glucose (normoglycemic but hyperinsulinemic), and 0.45% (wt/vol) saline (controls). A decrease in the islet content of PC2, PC3, and CP-H from hyperglycemic rats was observed. This reduction did not correlate with any deficiency in mRNA levels or biosynthesis of PC2, PC3, CP-H, or proinsulin. Furthermore, proinsulin conversion rate was comparable in islets from hyperglycemic and control rats. However, in islets from hyperglycemic rats an abnormal increased proportion of proinsulin was secreted, that was accompanied by an augmented release of PC2, PC3 and CP-H. Stimulation of the beta cell's secretory pathway by hyperglycemia, resulted in proinsulin being prematurely secreted from islets before its conversion could be completed. Thus, hyperproinsulinemia induced by chronic hyperglycemia likely results from increased beta cell secretory demand, rather than a defect in the proinsulin processing enzymes per se. PMID- 7883952 TI - DNA repair is more important than catalase for Salmonella virulence in mice. AB - Pathogenic microorganisms possess antioxidant defense mechanisms for protection from reactive oxygen metabolites such as hydrogen peroxide (H2O2), which are generated during the respiratory burst of phagocytic cells. These defense mechanisms include enzymes such as catalase, which detoxify reactive oxygen species, and DNA repair systems which repair damage resulting from oxidative stress. To determine the relative importance of these two potentially protective defense mechanisms against oxidative stress encountered by Salmonella during infection of the host, a Salmonella typhimurium double mutant unable to produce either the HPI or HPII catalase was constructed, and compared with an isogenic recA mutant deficient in DNA repair. The recA mutant was hypersusceptible to H2O2 at low cell densities in vitro, while the catalase mutant was more susceptible to high H2O2 concentrations at high cell densities. The catalase mutant was found to be resistant to macrophages and retained full murine virulence, in contrast to the recA mutant which previously was shown to be macrophage-sensitive and attenuated in mice. These observations suggest that Salmonella is subjected to low concentrations of H2O2 while at relatively low cell density during infection, conditions requiring an intact DNA repair system but not functional catalase activity. PMID- 7883953 TI - Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency. AB - We have recently described hereditary membranoproliferative glomerulonephritis type II in the pig. All affected animals had excessive complement activation, revealed as low plasma C3, elevated plasma terminal complement complex, and massive deposits of complement in the renal glomeruli, and eventually died of renal failure within 11 wk of birth. The aim of the present study was to investigate the cause of complement activation in this disease. Transfusion of normal porcine plasma to affected piglets inhibited complement activation and increased survival. Plasma was successively fractionated and the complement inhibitory effect of each fraction tested in vivo. A single chain 150-kD protein which showed the same complement inhibitory effect as whole plasma was finally isolated. Immunologic cross-reactivity, functional properties, and NH2-terminal sequence identified the protein as factor H. By Western blotting and enzyme immunoassay, membranoproliferative glomerulonephritis-affected piglets were demonstrated to be subtotally deficient in factor H. At 1 wk of age, median (range) factor H concentration was 1.6 mg/liter (1.1-2.3) in deficient animals (n = 13) and 51 mg/liter (26-98) in healthy littermates (n = 52). Our data show that hereditary porcine membrano-proliferative glomerulonephritis type II is caused by factor H deficiency. PMID- 7883954 TI - Heparin-enhanced plasma phospholipase A2 activity and prostacyclin synthesis in patients undergoing cardiac surgery. AB - Although eicosanoid production contributes to physiological and pathophysiological consequences of cardiopulmonary bypass (CPB), the mechanisms accounting for the enhanced eicosanoid production have not been defined. Plasma phospholipase A2 (PLA2) activity, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TXB2) levels were measured at various times during cardiac surgery. Plasma PLA2 activity increased after systemic heparinization, before CPB. This was highly correlated with concurrent increases in plasma 6-keto PGF1 alpha, TXB2 concentrations did not increase with heparin administration but did increase significantly after initiation of CPB. High plasma PLA2 activity, 6 keto-PGF1 alpha, and TXB2 concentrations were measured throughout the CPB period. Protamine, administered to neutralize the heparin, caused an acute reduction of both plasma PLA2 activity and plasma 6-keto-PGF1 alpha, but no change in plasma TXB2 concentrations. Thus the ratio of TXB2 to 6-keto-PGF1 alpha increased significantly after protamine administration. Enhanced plasma PLA2 activity was also measured in patients with lower doses of heparin used clinically for nonsurgical applications. Human plasma PLA2 was identified as group II PLA2 by its sensitivity to deoxycholate and dithiothreitol, its substrate specificity, and its elution characteristics on heparin affinity chromatography. Heparin addition to PMNs in vitro resulted in dose-dependent increases in cellular PLA2 activity and release of PLA2. The PLA2 released from the PMN had characteristics similar to those of post-heparin plasma PLA2. In conclusion, plasma PLA2 activity and 6-keto-PGF1 alpha concentrations are markedly enhanced with systemic heparinization. Part of the anticoagulant and vasodilating effects of heparin may be due to increased plasma prostacyclin (PGI2) levels. In addition the pulmonary vasoconstriction sometimes associated with protamine infusion during cardiac surgery might be due to decreased plasma PLA2 activity, with an associated increased TXB2/6-keto-PGF1 alpha ratio. PMID- 7883955 TI - Inhibition of leukocyte-endothelial cell interactions and inflammation by peptides from a bacterial adhesin which mimic coagulation factor X. AB - Factor X (factor ten) of the coagulation cascade binds to the integrin CD11b/CD18 during inflammation, initiating procoagulant activity on the surface of leukocytes (Altieri, D.C., O.R. Etingin, D.S. Fair, T.K. Brunk, J.E. Geltosky, D.P. Hajjar, and T. S. Edgington. 1991. Science [Wash.DC]. 254:1200-1202). Filamentous hemagglutinin (FHA), an adhesin of Bordetella pertussis also binds to the CD11b/CD18 integrin (Relman D., E. Tuomanen, S. Falkow, D.T. Golenbock, K. Saukkonen, and S.D. Wright. 1990. Cell. 61:1375-1382). FHA and the CD11b/CD18 binding loops of Factor X share amino acid sequence similarity. FHA peptides similar to Factor X binding loops inhibited 125I-Factor X binding to human neutrophils and prolonged clotting time. In addition, ETKEVDG and its Factor X analogue prevented transendothelial migration of leukocytes in vitro and reduced leukocytosis and blood brain barrier disruption in vivo. Interference with leukocyte migration by a coagulation-based peptide suggests a novel strategy for antiinflammatory therapy. PMID- 7883956 TI - Effect of recombinant human tumor necrosis factor-alpha on cerebral oxygen uptake, cerebrospinal fluid lactate, and cerebral blood flow in the rabbit: role of nitric oxide. AB - Among the important pathophysiologic alterations in the brain in bacterial meningitis are abnormalities of cerebral circulation and metabolism; however, the precise mechanisms by which these disturbances occur are not completely delineated. It has been recently recognized that cytokines are produced by tissues in the central nervous system in meningitis and play a critical role in the host inflammatory response. Because these mediators are involved in circulatory and metabolic disturbances in other tissues in sepsis, we investigated the role of tumor necrosis factor-alpha in the central nervous system in a rabbit model. We found that injection of recombinant human TNF into the cisterna magna in the rabbit led to an acute reduction in cerebral oxygen uptake and a more prolonged reduction in cerebral blood flow. This was accompanied by an increase in intracranial pressure and an increase in cerebrospinal fluid lactate. Reduction in oxygen uptake and increases in intracranial pressure and CSF lactate were blocked by pretreatment with L-NAME, an inhibitor of nitric oxide synthase. Reduction in cerebral blood flow was not affected by L-NAME treatment and was due to increased cerebrovascular resistance and reduced oxygen demand. These results suggest that TNF may be a critical mediator of changes in cerebral circulation and metabolism and that some of these changes occur via the nitric oxide pathway. PMID- 7883957 TI - Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction. AB - The purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. Hearts were isolated 8 wk later and buffer perfused isovolumically. MI hearts showed reduced left ventricular developed pressure, but oxygen consumption was unchanged. High-energy phosphate contents were measured chemically and by 31P-NMR spectroscopy. In residual intact left ventricular tissue, ATP was unchanged after MI, while creatine phosphate was reduced by 31%. Total creatine kinase (CK) activity was reduced by 17%, the fetal CK isoenzymes BB and MB increased, while the "adult" mitochondrial CK isoenzyme activity decreased by 44%. Total creatine content decreased by 35%. Phosphoryl exchange between ATP and creatine phosphate, measured by 31P-NMR magnetization transfer, fell by 50% in MI hearts. Thus, energy reserve is substantially impaired in residual intact myocardium of chronically infarcted rats. Because phosphoryl exchange was still five times higher than ATP synthesis rates calculated from oxygen consumption, phosphoryl transfer via CK may not limit baseline contractile performance 2 mo after MI. In contrast, when MI hearts were subjected to acute stress (hypoxia), mechanical recovery during reoxygenation was impaired, suggesting that reduced energy reserve contributes to increased susceptibility of MI hearts to acute metabolic stress. PMID- 7883958 TI - A functional role for endogenous atrial natriuretic peptide in a canine model of early left ventricular dysfunction. AB - Asymptomatic or early left ventricular dysfunction in humans is characterized by increases in circulating atrial natriuretic peptide (ANP) without activation of the renin-angiotensin-aldosterone system (RAAS). We previously reported a canine model of early left ventricular dysfunction (ELVD) produced by rapid ventricular pacing and characterized by an identical neurohumoral profile and maintenance of the natriuretic response to volume expansion (VE). To test the hypothesis that elevated endogenous ANP suppresses the RAAS and maintains sodium excretion in ELVD, we assessed the effects of antagonism of ANP on cardiorenal and neurohumoral function in ELVD. Chronic ANP suppression was produced by bilateral atrial appendectomies before the production of ELVD by rapid ventricular pacing (ELVD-APPX, n = 5). This group was compared with a separate group with ELVD and intact atrial appendages (ELVD-INTACT, n = 8). ELVD-APPX was characterized by lower circulating ANP (50 +/- 11 vs. 158 +/- 37 pg/ml, P < 0.05), activation of plasma renin activity (PRA) (9.4 +/- 2.4 vs. 0.6 +/- 0.4 ng/ml per h, P < 0.05) and aldosterone (36.4 +/- 12.5 vs. 2.5 +/- 0.0 ng/dl, P < 0.05) when compared to ELVD-INTACT. In comparison to the ELVD-INTACT group, sodium excretion was decreased before and during VE in the ELVD-APPX group. Acute ANP antagonism was produced by administration of the particulate guanylate cyclase coupled natriuretic peptide receptor antagonist, HS-142-1, to seven conscious dogs with ELVD and intact atrial appendages (ELVD-INTACT). HS-142-1 decreased plasma concentrations and renal generation of the ANP second messenger, cGMP, and was associated with activation of PRA and sodium retention with enhanced tubular sodium reabsorption. These data support a significant role for elevated endogenous ANP in the maintenance of sodium excretion and regulation of the RAAS in experimental ELVD. PMID- 7883959 TI - A pathogenic role of visceral fat beta 3-adrenoceptors in obesity. AB - Increased release of free fatty acids (FFA) from visceral fat cells to the portal venous system may cause several metabolic disturbances in obesity. However, this hypothesis and the underlying mechanism remain to be demonstrated. In this study catecholamine-induced lipid mobilization through lipolysis in omental adipose tissue was investigated in vitro in 25 markedly obese subjects (body mass index range 35-56 kg/m2) undergoing weight reduction surgery and in 19 nonobese subjects (body mass index range 20-28 kg/m2) undergoing cholecystectomy. Release of FFA and glycerol, induced by norepinephrine or adrenergic receptor subtype specific agonists, were determined in isolated omental fat cells. The obese subjects had higher fat cell volume, blood pressure, plasma insulin levels, blood glucose, plasma triglycerides, and plasma cholesterol than the controls. There was evidence of upper-body fat distribution in the obese group. The rate of FFA and glycerol response to norepinephrine was increased twofold in the cells of obese subjects; no significant reutilization of FFA during catecholamine-induced lipolysis was observed in any of the groups (glycerol/FFA ratio near 1:3). There were no differences in the lipolytic sensitivity to beta 3- or beta 2 adrenoceptor specific agonists between the two groups. However, beta 3 adrenoceptor sensitivity was approximately 50 times enhanced (P = 0.0001), and the coupling efficiency of these receptors was increased from 37 to 56% (P = 0.01) in obesity. Furthermore, the obese subjects demonstrated a sixfold lower alpha 2-adrenoceptor sensitivity (P = 0.04). beta 3-Adrenoceptor sensitivity, but not alpha 2-, beta 1-, or beta 2-adrenoceptor sensitivity, correlated with norepinephrine-induced lipolysis (r = -0.67, P = 0.0001) and fat cell volume (r = -0.71, P = 0.0001). In conclusion, catecholamine-induced rate of FFA mobilization from omental fat cells is accelerated due to elevated rate of lipolysis in obesity, mainly because of an increased beta 3-adrenoceptor function, but partly also because of a decreased alpha 2-adrenoceptor function. This promotes an increased release of FFA to the portal system, which may contribute to the parallel metabolic disturbances observed in upper-body obesity. PMID- 7883960 TI - Telomeric DNA in normal and leukemic blood cells. AB - We studied telomeric DNA in leukemic cells as well as in normal T cells, B cells, monocytes, polymorphonuclear leukocytes, and bone marrow hematopoietic progenitor cells. No marked differences were observed in the sizes of the telomeric repeats in the various populations of normal blood cells obtained from donors in their twenties to sixties, and the telomere length ranged between 8.5 and 9.0 kb. The leukemic cells of 12 patients with acute leukemia (seven with myeloid and five with lymphoid leukemia) showed a variable reduction in the length of telomeric DNA, ranging from 2.7 to 6.4 kb. The average telomere length was 4.8 and 4.7 kb in myeloid and lymphoid leukemia, respectively, while the telomere length in peripheral blood mononuclear cells obtained from the same patients during complete remission was 8.5 and 7.9 kb, respectively. When the same Southern blots were hybridized with Alu or alphoid sequences, no marked changes in the sizes of the repetitive DNA sequences were observed, indicating that the DNA abnormality in the leukemic cells was specific to the telomere region. Investigation of telomeric DNA changes may be helpful in determining the biological properties of leukemic cells. PMID- 7883961 TI - Role of the low density lipoprotein receptor in the flux of cholesterol through the plasma and across the tissues of the mouse. AB - These studies were undertaken to quantify cholesterol balance across the plasma space and the individual organs of the mouse, and to determine the role of the low density lipoprotein receptor (LDLR) in these two processes. In the normal mouse (129 Sv), sterol was synthesized at the rate of 153 mg/d per kg body weight of which 78% occurred in the extrahepatic tissues while only 22% took place in the liver. These animals metabolized 7.1 pools of LDL-cholesterol (LDL-C) per day, and 79% of this degradation took place in the liver. Of this total turnover, the LDLR accounted for 88% while the remaining 12% was receptor independent. 91% of the receptor-dependent transport identified in these animals was located in the liver while only 38% of the receptor-independent uptake wsa found in this organ. When the LDLR was deleted, the LDL-C production rate increased 1.7-fold, LDL-C turnover decreased from 7.1 to 0.88 pools/d, and the plasma LDL-C level increased 14-fold, from 7 to 101 mg/dl. Despite these major changes in the circulating levels of LDL-C, however, there was no change in the rate of cholesterol synthesis in any extrahepatic organ or in the whole animal, and, further, there was no change in the steady-state cholesterol concentration in any organ. Thus, most extrahepatic tissues synthesize their daily sterol requirements while most LDL-C is returned directly to the liver. Changes in LDLR activity, therefore, profoundly alter the plasma LDL-C concentration but have virtually no affect on cholesterol balance across any extrahepatic organ, including the brain. PMID- 7883962 TI - Induction of sustained expression of proto-oncogene c-fms by platelet-derived growth factor, epidermal growth factor, and basic fibroblast growth factor, and its suppression by interferon-gamma and macrophage colony-stimulating factor in human aortic medial smooth muscle cells. AB - Vascular medial smooth muscle cells migrate, proliferate and transform to foam cells in the process of atherosclerosis. We have reported that the intimal smooth muscle cells express proto-oncogene c-fms, a characteristic gene of monocyte macrophages, which is not normally expressed in medial smooth muscle cells. In the present study, we demonstrated that combinations of platelet-derived growth factor (PDGF)-BB and either epidermal growth factor (EGF) or fibroblast growth factor (FGF) induced high expression of c-fms in normal human medial smooth muscle cells to the level of intimal smooth muscle cells or monocyte-derived macrophages, whereas c-fms expression by PDGF-BB alone was 1/10 and both EGF and FGF had no independent effect on c-fms expression. By contrast, interferon (IFN) gamma and macrophage colony-stimulating factor (M-CSF) suppressed the induction of c-fms expression. These results indicate that multiple growth factors and cytokines may play a role in the phenotypic transformation of medial smooth muscle cells to intimal smooth muscle cells in atherosclerotic lesions by altering c-fms expression. PMID- 7883963 TI - Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy. AB - To clarify the role of PDGF A-chain in hypertensive vascular hypertrophy of spontaneously hypertensive rats (SHRs), we studied levels of PDGF A-chain gene expression and transcription factors related to the gene in vascular smooth muscle cells (VSMCs) of SHRs in vivo. RNase protection assay and in situ hybridization showed that PDGF A-chain mRNA levels in VSMCs of SHRs were twofold higher than in those of normotensive Wistar-Kyoto rats. Gel retardation assays showed that levels of Sp1 and AP-2 in VSMCs of SHRs were twofold more abundant than in those of Wistar-Kyoto rats. Treatment with four pharmacologically different species of antihypertensive drugs for 2 wk decreased the levels of both PDGF A-chain mRNA and Sp1, but not AP-2 level in VSMCs of SHRs with regression of aortic hypertrophy, indicating that increases in levels of both PDGF A-chain mRNA and Sp1 in VSMCs of SHRs were associated with high blood pressure. These results suggest that high blood pressure is a stimulus which upregulates PDGF A-chain gene expression in VSMCs of SHRs, resulting in an autocrine enhancement in hypertensive vascular hypertrophy, and that the activation of the gene may be mediated through increases in Sp1 in these cells. PMID- 7883964 TI - Atrial and brain natriuretic peptides stimulate the production and secretion of C type natriuretic peptide from bovine aortic endothelial cells. AB - C-type natriuretic peptide (CNP) is a member of the natriuretic peptide family which is produced in vascular endothelial cells and may play an important paracrine role in the vasaculature. We sought to determine the regulation of CNP production by other vasoactive peptides from cultured aortic endothelial cells. The vasoconstrictors endothelin-1 and angiotensin II had little effect on the basal secretion of CNP. In contrast, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) strongly stimulated the secretion of CNP. BNP caused as much as a 400-fold enhancement above the basal accumulated secretion of CNP over 24 h at a concentration of 1 microM; this was 20 times greater than the stimulatory effect of ANP, BNP and ANP also significantly enhanced the production of new CNP protein (translation) and mRNA expressed in the BAEC. In contrast, C ANP-4-23, a truncated form of ANP which selectively binds to the natriuretic peptide clearance receptor, did not stimulate CNP secretion. The enhanced production and secretion of CNP, caused by either ANP or BNP, was significantly prevented by LY 83583, an inhibitor of cGMP generation, and was also attenuated by KT 5823, an inhibitor of cGMP-dependent protein kinase. Our results indicate that ANP and BNP can stimulate CNP production through a guanylate cyclase receptor on endothelial cells. BNP is a much more potent stimulator of CNP secretion, compared to ANP. Our findings suggest that the vasodilatory, and anti mitogenic effects of ANP and BNP in the vasculature could occur in part through CNP production and subsequent action if these interactions occur in vivo. PMID- 7883965 TI - Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency. AB - Clinical and immunologic features of a recently recognized X-linked combined immunodeficiency disease (XCID) suggested that XCID and X-linked severe combined immunodeficiency (XSCID) might arise from different genetic defects. The recent discovery of mutations in the common gamma chain (gamma c) gene, a constituent of several cytokine receptors, in XSCID provided an opportunity to test directly whether a previously unrecognized mutation in this same gene was responsible for XCID. The status of X chromosome inactivation in blood leukocytes from obligate carriers of XCID was determined from the polymorphic, short tandem repeats (CAG), in the androgen receptor gene, which also contains a methylation-sensitive HpaII site. As in XSCID, X-chromosome inactivation in obligate carriers of XCID was nonrandom in T and B lymphocytes. In addition, X chromosome inactivation in PMNs was variable. Findings from this analysis prompted sequencing of the gamma c gene in this pedigree. A missense mutation in the region coding for the cytoplasmic portion of the gamma c gene was found in three affected males but not in a normal brother. Therefore, this point mutation in the gamma c gene leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID. PMID- 7883966 TI - Recurrent fatal hydrops fetalis associated with a nucleotide substitution in the erythrocyte beta-spectrin gene. AB - We studied a kindred in which four third-trimester fetal losses occurred, associated with severe Coombs-negative hemolytic anemia and hydrops fetalis. Postmortem examination of two infants revealed extensive extramedullary erythropoiesis. Studies of erythrocytes and erythrocyte membranes from the parents revealed abnormal erythrocyte membrane mechanical stability as well as structural and functional abnormalities in spectrin, the principal structural protein of the erythrocyte membrane. Genetic studies identified a point mutation of the beta-spectrin gene, S2019P, in a region of beta spectrin that is critical for normal spectrin function. Both parents and two living children were heterozygous for this mutation; three infants dying of hydrops fetalis were homozygous for this mutation. In an in vitro assay using recombinant peptides, the mutant beta-spectrin peptide demonstrated a significant abnormality in its ability to interact with alpha spectrin. This is the first description of a molecular defect of the erythrocyte membrane associated with hydrops fetalis. PMID- 7883967 TI - Effect of granulocyte-macrophage colony-stimulating factor in experimental visceral leishmaniasis. AB - GM-CSF induces three effects potentially beneficial in visceral leishmaniasis: blood monocyte mobilization, macrophage activation, and amelioration of granulocytopenia. To determine the experimental role and effect of GM-CSF in this intracellular infection, livers from Leishmania donovani-infected BALB/c mice were tested for GM-CSF mRNA expression and mice were treated with anti-GM-CSF antiserum or GM-CSF. L. donovani infection upregulated hepatic GM-CSF mRNA expression by 10-fold, and anti-GM-CSF treatment exacerbated visceral infection and tripled liver parasite burdens 4 wk after challenge. In euthymic mice with established infection, treatment with 1-5 micrograms/d murine GM-CSF induced three dose-related effects: peripheral blood leukocytosis, preferential accumulation of myelomonocytic cells at visceral foci of infection, and leishmanicidal activity comparable to that achieved by IFN-gamma. These effects were either largely or entirely T cell dependent. Treatment with human GM-CSF also induced anti-leishmanial activity but with little effect on peripheral leukocyte number or tissue myelomonocytic cell influx; human G-CSF stimulated marked peripheral granulocytosis and neutrophil tissue accumulation but induced little antileishmanial effect. These results identify a role for endogenous GM CSF in the initial host defense response to L. donovani, reemphasize the influxing monocyte as an effector cell, and indicate that GM-CSF can be used as an antileishmanial treatment. PMID- 7883968 TI - Cross-resistance between cisplatin, antimony potassium tartrate, and arsenite in human tumor cells. AB - Cross-resistance between cisplatin (DDP) and metalloid salts in human cells was sought on the basis that mechanisms that mediate metalloid salt cross-resistance in prokaryotes are evolutionarily conserved. Two ovarian and two head and neck carcinoma cell lines selected for DDP resistance were found to be cross-resistant to antimony potassium tartrate, which contains trivalent antimony. The DDP resistant variant 2008/A was also cross-resistant to arsenite but not to stibogluconate, which contains pentavalent antimony. A variant selected for resistance to antimony potassium tartrate was cross-resistant to DDP and arsenite. Resistance to antimony potassium tartrate and arsenite was of a similar magnitude (3-7-fold), whereas the level of resistance to DDP was greater (17 fold), irrespective of whether the cells were selected by exposure to DDP or to antimony potassium tartrate. In the resistant sublines, uptake of [3H] dichloro(ethylenediamine) platinum(II) was reduced to 41-52% of control, and a similar deficit was observed in the accumulation of arsenite. We conclude that DDP, antimony potassium tartrate, and arsenite all share a common mechanism of resistance in human cells and that this is due in part to an accumulation defect. PMID- 7883969 TI - The purinergic P2Z receptor of human macrophage cells. Characterization and possible physiological role. AB - We have investigated responses of human monocyte/macrophage cells to extracellular ATP (ATPe). Freshly isolated peripheral blood monocytes showed responses linked to P2Y but not P2Z purinergic receptors; however, during in vitro macrophage differentiation, these cells also exhibited responses suggestive of the presence of the membrane-permeabilizing P2Z receptor. In fact, in human macrophages a brief (15-min) exposure to ATPe, but not other nucleotides, caused (1) a rapid and long-lasting plasma membrane depolarization; (2) a large increase in intracellular Ca2+ concentration followed by efflux of the Ca2+ indicator; (3) uptake of low molecular weight hydrophilic molecules such as Lucifer yellow and ethidium bromide; and (4) cell rounding, swelling, and eventual release of the cytoplasmic enzyme lactate dehydrogenase. rIFN-gamma enhanced both membrane permeabilizing and cytotoxic ATPe effects. Membrane permeabilization and cytotoxicity were fully blocked by pretreatment of the cells with oxidized ATP, a compound recently shown to block P2Z receptors covalently in macrophages. Blocking of the P2Z receptor by oxidized ATP also inhibited multinucleated giant cell generation stimulated by concanavalin A or rIFN-gamma without decreasing monocyte migration or membrane adhesion molecule expression. These data suggest that human macrophages express rIFN-gamma-modulated purinergic P2Z receptors in vitro and hint at a role for these plasma membrane molecules in the generation of macrophage polykarions. PMID- 7883970 TI - Decreased stress responsivity of central and peripheral catecholaminergic systems in aged 344/N Fischer rats. AB - We investigated the effects of stress on central and peripheral sympatho-adrenal and sympatho-neural functions in healthy, intact young (3-4 mo) and aged (24 mo) male Fischer 344/N rats. Extracellular fluid (ECF) levels of the catecholamines norepinephrine (NE), dihydroxyphenylglycol (DHPG), methoxyhydroxyphenylglycol (MHPG), and dihydroxyphenylacetic acid (DOPAC) were obtained by microdialysis in the paraventricular nucleus (PVN) of the hypothalamus at baseline and during immobilization (IMMO). The baseline levels of these substances were similar in both age groups, and their concentrations increased significantly in response to IMMO. The IMMO-induced increases of NE and MHPG, however, were significantly smaller in old than in young rats. Plasma levels of the catecholamines NE, DHPG, MHPG, DOPAC, dihydroxyphenylalanine (DOPA), epinephrine (EPI), dopamine (DA), and HVA were also determined in young and old rats during IMMO. Basal levels of these substances were significantly higher in old than in young rats. The magnitude of the IMMO-induced increases in the majority of these compounds however, was significantly smaller in old than in young rats. We conclude that, at the basal state, aging in the Fischer rat is associated with normal PVN ECF, but high plasma catecholamine levels; at stress state, however, old rats have substantially lesser activation of their central and peripheral catecholaminergic systems than young rats. PMID- 7883971 TI - Familial ligand-defective apolipoprotein B. Identification of a new mutation that decreases LDL receptor binding affinity. AB - Detection of new ligand-defective mutations of apolipoprotein B (apoB) will enable identification of sequences involved in binding to the LDL receptor. Genomic DNA from patients attending a lipid clinic was screened by single-strand conformation polymorphism analysis for novel mutations in the putative LDL receptor-binding domain of apoB-100. A 46-yr-old woman of Celtic and Native American ancestry with primary hypercholesterolemia (total cholesterol [TC] 343 mg/dl; LDL cholesterol [LDL-C] 241 mg/dl) and pronounced peripheral vascular disease was found to be heterozygous for a novel Arg3531-->Cys mutation, caused by a C-->T transition at nucleotide 10800. One unrelated 59-yr-old man of Italian ancestry was found with the same mutation after screening 1,560 individuals. He had coronary heart disease, a TC of 310 mg/dl, and an LDL-C of 212 mg/dl. A total of eight individuals were found with the defect in the families of the two patients. They had an age- and sex-adjusted TC of 240 +/- 14 mg/dl and LDL-C of 169 +/- 10 mg/dl. This compares with eight unaffected family members with age- and sex-adjusted TC of 185 +/- 12 mg/dl and LDL-C of 124 +/- 12 mg/dl. In a dual label fibroblast binding assay, LDL from the eight subjects with the mutation had an affinity for the LDL receptor that was 63% that of control LDL. LDL from eight unaffected family members had an affinity of 91%. By way of comparison, LDL from six patients heterozygous for the Arg3500-->Gln mutation had an affinity of 36%. The percentage mass ratio of the defective Cys3531 LDL to normal LDL was 59:41, as determined using the mAb MB19 and dynamic laser light scattering. Thus, the defective LDL had accumulated in the plasma of these patients. Using this mass ratio, it was calculated that the defective Cys3531 LDL particles bound with 27% of normal affinity. Deduced haplotypes using 10 apoB gene markers showed the Arg3531-->Cys alleles to be different in the two kindreds and indicates that the mutations arose independently. The Arg3531-->Cys mutation is the second reported cause of familial ligand-defective apoB. PMID- 7883972 TI - Heterogeneous expression of cholesterol 7 alpha-hydroxylase and sterol 27 hydroxylase genes in the rat liver lobulus. AB - We investigated the lobular localization and molecular level of expression of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase, two key enzymes in bile acid synthesis, in isolated periportal and pericentral hepatocytes and by in situ hybridization of rat liver. Enzyme activity, mRNA, and gene transcription of cholesterol 7 alpha-hydroxylase were predominant in pericentral hepatocytes of control rats, being 7.9-, 9.9-, and 4.4-fold higher than in periportal hepatocytes, respectively. Similar localization was found for sterol 27 hydroxylase: 2.9-, 2.5-, and 1.7-fold higher enzyme activity, mRNA, and gene transcription, respectively, was found in pericentral hepatocytes. Interruption of the enterohepatic circulation with colestid resulted in upregulation of these parameters for both enzymes, as a consequence of stimulated gene expression mainly in the periportal zone. In contrast, mRNA levels and gene transcription of 3-hydroxy-3-methylglutaryl CoA reductase showed opposite lobular distribution. Selective periportal expression for the latter was enhanced, but remained local, after colestid treatment. In situ hybridization showed unambiguously that cholesterol 7 alpha-hydroxylase mRNA is localized exclusively in the pericentral zone and that sterol 27-hydroxylase mRNA is expressed preferentially in the pericentral region, though less pronounced. Administration of colestid led to expression of both genes within a larger area of the liver lobulus. In conclusion, we suggest that cholesterol 7 alpha-hydroxylase and sterol 27 hydroxylase are coordinately regulated by the bile acid gradient over the lobulus, resulting in predominant expression in the pericentral zone. Opposite lobular localization of cholesterol and bile acid synthesis provides an alternative view to interregulation of these metabolic pathways. PMID- 7883973 TI - Activation of mesangial cells by the phosphatase inhibitor vanadate. Potential implications for diabetic nephropathy. AB - The metalion vanadate has insulin-like effects and has been advocated for use in humans as a therapeutic modality for diabetes mellitus. However, since vanadate is a tyrosine phosphatase inhibitor, it may result in undesirable activation of target cells. We studied the effect of vanadate on human mesangial cells, an important target in diabetic nephropathy. Vanadate stimulated DNA synthesis and PDGF B chain gene expression. Vanadate also inhibited total tyrosine phosphatase activity and stimulated tyrosine phosphorylation of a set of cellular proteins. Two chemically and mechanistically dissimilar tyrosine kinase inhibitors, genistein and herbimycin A, blocked DNA synthesis induced by vanadate. Vanadate also stimulated phospholipase C and protein kinase C. Downregulation of protein kinase C abolished vanadate-induced DNA synthesis. Thus, vanadate-induced mitogenesis is dependent on tyrosine kinases and protein kinase C activation. The most likely mechanism for the effect of vanadate on these diverse processes involves the inhibition of cellular phosphotyrosine phosphatases. These studies demonstrating that vanadate activates mesangial cells may have major implications for the therapeutic potential of vanadate administration in diabetes. Although vanadate exerts beneficial insulin-like effects and potentiates the effect of insulin in sensitive tissue, it may result in undesirable activation of other target cells, such as mesangial cells. PMID- 7883974 TI - Kinetic modeling and mathematical analysis indicate that acute phase gene expression in Hep 3B cells is regulated by both transcriptional and posttranscriptional mechanisms. AB - To evaluate the possible role of posttranscriptional mechanisms in the acute phase response, we determined the kinetics of transcription (by nuclear run-on assay) and mRNA accumulation of five human acute phase genes in Hep 3B cells incubated with conditioned medium from LPS-stimulated monocytes. Increase in mRNA accumulation was comparable to increase in transcription rate for fibrinogen alpha and alpha-1 protease inhibitor, suggesting largely transcriptional regulation. In contrast, mRNA accumulation was about 10-20-fold greater than transcriptional increase for serum amyloid A, C3, and factor B, suggesting participation of posttranscriptional mechanisms. Since finding a disparity between the magnitudes of increase in mRNA and transcription does not definitively establish involvement of posttranscriptional mechanisms, we subjected our data to modeling studies and dynamic mathematical analysis to evaluate this possibility more rigorously. In modeling studies, accumulation curves resembling those observed for these three mRNAs could be generated from the nuclear run-on results only if posttranscriptional regulation was assumed. Dynamic mathematical analysis of relative transcription rates and relative mRNA abundance also strongly supported participation of posttranscriptional mechanisms. These observations suggest that posttranscriptional regulation plays a substantial role in induction of some, but not all acute phase proteins. PMID- 7883975 TI - Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart. AB - To determine whether beta-adrenergic receptor agonist activation influences guanosine 5'-triphosphate-binding protein (G-protein) expression and beta adrenergic receptor kinase activity in the heart, we examined the effects of chronic beta 1-adrenergic receptor antagonist treatment (bisoprolol, 0.2 mg/kg per d i.v., 35 d) on components of the myocardial beta-adrenergic receptor-G protein-adenylyl cyclase pathway in porcine myocardium. Three novel alterations in cardiac adrenergic signaling associated with chronic reduction in beta adrenergic receptor agonist activation were found. First, there was coordinate downregulation of Gi alpha 2 and Gs alpha mRNA and protein expression in the left ventricle; reduced G-protein content was also found in the right atrium. Second, in the left ventricle, there was a twofold increase in beta-adrenergic receptor dependent stimulation of adenylyl cyclase and a persistent high affinity state of the beta-adrenergic receptor. Finally, there was a reduction in left ventricular beta-adrenergic receptor kinase activity, suggesting a previously unrecognized association between the degree of adrenergic activation and myocardial beta adrenergic receptor kinase expression. The heart appears to adapt in response to chronic beta-adrenergic receptor antagonist administration in a manner that would be expected to offset reduced agonist stimulation. The mechanisms for achieving this extend beyond beta-adrenergic receptor upregulation and include alterations in G-protein expression, beta-adrenergic receptor-Gs interaction, and myocardial beta-adrenergic receptor kinase activity. PMID- 7883976 TI - An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance. AB - The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population. A polymorphism at codon 54 of FABP2 was identified that results in an alanine-encoding allele (frequency 0.71) and a threonine-encoding allele (frequency 0.29). Pimas who were homozygous or heterozygous for the threonine encoding allele were found to have a higher mean fasting plasma insulin concentration, a lower mean insulin-stimulated glucose uptake rate, a higher mean insulin response to oral glucose and a mixed meal, and a higher mean fat oxidation rate compared with Pimas who were homozygous for the alanine-encoding allele. Since the FABP2 threonine-encoding allele was found to be associated with insulin resistance and increased fat oxidation in vivo, we further analyzed the FABP2 gene products for potential functional differences. Titration microcalorimetry studies with purified recombinant protein showed that the threonine-containing protein had a twofold greater affinity for long-chain fatty acids than the alanine-containing protein. We conclude that the threonine containing protein may increase absorption and/or processing of dietary fatty acids by the intestine and thereby increase fat oxidation, which has been shown to reduce insulin action. PMID- 7883978 TI - Unique C1 inhibitor dysfunction in a kindred without angioedema. II. Identification of an Ala443-->Val substitution and functional analysis of the recombinant mutant protein. AB - We have determined the cause of an unusual C1 inhibitor abnormality in a large kindred. We previously found that half of serum C1 inhibitor molecules in affected kindred members are normal. The other half complexed with C1s but showed little complex formation with C1r. These molecules also appeared to be relatively resistant to digestion by trypsin. Taken together, the findings suggested that members of this kindred are heterozygous for an unusual C1 inhibitor mutation. Sequencing of genomic DNA from the kindred revealed that thymine has replaced cytosine in the codon for Ala443 (P2 residue) in one C1 inhibitor allele, resulting in substitution with a Val residue. To test the effect of this substitution, a mutant C1 inhibitor containing Ala443-->Val was constructed by site-directed mutagenesis and expressed in COS-1 cells. Both the Ala443-->Val mutant and the wild-type C1 inhibitor complexed completely with C1s, kallikrein, and coagulation Factor XIIa after incubation at 37 degrees C for 60 min. In contrast, the mutant inhibitor failed to complex completely with C1r under the same conditions. Time course analysis showed that the ability of the mutant to complex with C1s is also impaired: although it complexed completely in 60 min, the rate of complex formation during a 0-60-min incubation was decreased compared with wild-type C1 inhibitor. The mutant inhibitor also formed a complex with trypsin, a serine protease that cleaves, and is not inhibited by, wild-type C1 inhibitor. The Ala443-->Val mutation therefore converts C1 inhibitor from a substrate to an inhibitor of trypsin. These studies emphasize the role of the P2 residue in the determination of target protease specificity. PMID- 7883977 TI - Human and murine pituitary expression of leukemia inhibitory factor. Novel intrapituitary regulation of adrenocorticotropin hormone synthesis and secretion. AB - Leukemia inhibitory factor (LIF) gene expression was detected in human fetal pituitary tissue by expression of LIF mRNA transcripts, protein immunocytochemistry, and immunoelectron microscopy. Fetal LIF immunoreactivity colocalized with 30% of ACTH-expressing cells, approximately 20% of somatotrophs, and approximately 15% of non-hormone-expressing cells. LIF was also strongly expressed in normal adult pituitary and in four growth hormone-producing and two ACTH-producing adenomas, but not in eight nonfunctioning pituitary tumors. Culture of fetal cells expressing surface LIF-binding sites demonstrated predominance of in vitro ACTH secretion as compared with other pituitary hormones. In AtT-20 murine cells, LIF (ED50 10 pM) stimulated basal proopiomelanocortin mRNA levels by 40% and corticotropin-releasing hormone induced ACTH secretion (two- to threefold), as did oncostatin M (ED50 30 pM), a related peptide. ACTH responses were not further enhanced by both cytokines together, which is consistent with their shared receptor. Anti-LIF antiserum neutralized basal and LIF-induced ACTH secretion, suggesting autocrine regulation of ACTH by LIF. The results show that human pituitary cells express the LIF gene and LIF-binding sites, predominantly in corticotrophs. Pituitary LIF expression and LIF regulation of proopiomelanocortin and ACTH reflect an intrapituitary role for LIF in modulating early embryonic determination of specific human pituitary cells and as a paracrine or autocrine regulator of mature ACTH. PMID- 7883979 TI - Premature termination codons on both alleles of the type VII collagen gene (COL7A1) in three brothers with recessive dystrophic epidermolysis bullosa. AB - Epidermolysis bullosa (EB) is a group of heritable mechano-bullous skin diseases classified into three major categories on the basis of the level of tissue separation within the dermal-epidermal basement membrane zone. In the most severe, dystrophic (scarring) forms of EB, blisters form below the cutaneous basement membrane at the level of the anchoring fibrils, which are composed of type VII collagen. Ultrastructural observations of altered anchoring fibrils and genetic linkage to the type VII collagen locus (COL7A1) have implicated COL7A1 as the candidate gene in the dystrophic forms of EB. We have recently cloned the entire cDNA and the gene for human COL7A1. In this study, we describe distinct mutations in both COL7A1 alleles in three brothers with severe, mutilating recessive dystrophic EB (the Hallopeau-Siemens type, HS-RDEB). The patients are compound heterozygotes for two different mutations, both of which result in a premature termination codon in COL7A1, and the parents were shown to be clinically heterozygous carries of the respective mutations. Premature termination codons in both alleles of COL7A1 appear to be the underlying cause of severe, recessive dystrophic EB in this family. PMID- 7883980 TI - Targeting gene expression to the vascular wall in transgenic mice using the murine preproendothelin-1 promoter. AB - To develop a system for overexpressing genes in the vascular wall, we created transgenic mice using the reporter gene luciferase and the murine preproendothelin-1 promoter. In vitro analysis suggested that the murine 5' flanking region contained endothelial-specific elements in a 5.9-kb fragment. Five transgenic mice colonies established from independent founders all exhibited the highest level of luciferase activity in the aorta with up to 8,540 light units per microgram of protein. Immunohistochemistry with anti-luciferase antisera revealed high levels of expression in the endothelial cells of both large and small arteries and lower levels of expression in veins and capillaries. Significant expression was also seen in arterial smooth muscle cells and in select epithelial surfaces which is consistent with the known distribution of endothelin-1 in mammals. The further demonstrate the targeting capability of this system, we overexpressed the lipid-peroxidating enzyme, human 15-lipoxygenase, in the vessel wall of transgenic mice. As with luciferase, expression of active enzyme and immunohistochemical localization in vascular cells were documented in transgenic animals. Hence, this new system can be used to direct expression of molecules to the vascular wall for the purpose of examining the biological significance of either overexpression or inhibition of select proteins. PMID- 7883981 TI - 180-kD bullous pemphigoid antigen (BP180) is deficient in generalized atrophic benign epidermolysis bullosa. AB - Generalized atrophic benign epidermolysis bullosa (GABEB) is a form of nonlethal junctional epidermolysis bullosa characterized by universal alopecia and atrophy of the skin. We report a deficiency of the 180-kD bullous pemphigoid antigen in three patients with GABEB from unrelated families. We screened specimens of clinically normal skin from nine junctional epidermolysis bullosa patients (3 GABEB, 4 lethal, 1 cicatricial, 1 pretibial) by immunofluorescence using monoclonal antibodies to the 180-kD and 230-kD bullous pemphigoid antigens (BP180 and BP230). In the skin of the three GABEB patients there was no reactivity with antibodies to BP180, whereas staining for BP230 was normal. In the skin of the other six, non-GABEB patients, included in this study the expression of BP180 and BP230 was normal. Immunoblot analysis of cultured keratinocytes from one of the GABEB patients also failed to detect BP180 antigen, whereas BP230 was present in normal amounts. The deficient expression of BP180 is reflected in the RNA message, as in Northern blot analysis a reduced amount of BP180 transcripts, although of normal length, were detected. Interestingly, in another GABEB patient there were not-involved areas of skin, in which blistering could not be induced by rubbing. Biopsy material from these areas showed interrupted staining for BP180. There was no staining for BP180 in areas of clinically normal but involved skin of this patient. In conclusion, this study reveals that the BP180 antigen is deficient and the BP180 mRNA is reduced in generalized atrophic benign epidermolysis bullosa. PMID- 7883982 TI - Angiotensin II induces plasminogen activator inhibitor-1 and -2 expression in vascular endothelial and smooth muscle cells. AB - Angiotensin II (AII)- and Arg8-vasopressin (AVP)-regulated gene expression in vascular cells has been reported to contribute to vascular homeostasis and hypertrophy. In this report, AVP-induced expression of plasminogen activator inhibitor (PAI)-2 mRNA in rat microvessel endothelial (RME) cells was identified using differential mRNA display. Further characterization of vasoactive peptide effects on PAI expression revealed that AII stimulated a 44.8 +/- 25.2-fold and a 12.4 +/- 3.2-fold increase in PAI-2 mRNA in RME cells and rat aortic smooth muscle cells (RASMC), respectively. AII also stimulated a 10- and 48-fold increase in PAI-1 mRNA in RME cells and RASMC, respectively. These AII effects were inhibited by either Sar1, Ile8-angiotensin or the AT1 antagonist DuP 735, but were not significantly altered in the presence of the AT2 antagonist PD123319. AII stimulation of RASMC and RME cells also significantly increased both PAI-1 protein and PAI activity released to the culture medium. Inhibition of protein kinase C completely blocked PMA-stimulated induction of PAI-2 mRNA in both cell types and inhibited the AII-stimulated increase in RASMC by 98.6 +/- 2.8%. In contrast, protein kinase C inhibition only partially decreased the AII stimulated PAI-2 expression in RME cells by 68.8 +/- 11.1%, suggesting that a protein kinase C-independent mechanism contributes to a 6.9 +/- 1.5-fold AII induction of PAI-2 expression in endothelial cells. AII and PMA also stimulated protein tyrosine phosphorylation in RME cells, and the tyrosine kinase inhibitor genistein partially blocked their induction of PAI-2 mRNA. These findings suggest that AII may regulate plasminogen activation in the vasculature by inducing both PAI-1 and PAI-2 expression. PMID- 7883984 TI - Monocyte chemotactic protein-1 (MCP-1), -2, and -3 are chemotactic for human T lymphocytes. AB - Monocyte chemotactic protein (MCP)-1, -2, and -3 all have been shown to induce monocyte/macrophage migration in vitro and MCP-1, also known as MCAF, chemoattracts basophils and mast cells. We report here that natural MCP-1 as well as synthetic preparations of MCP-2 and MCP-3 stimulate significant in vitro chemotaxis of human peripheral blood T lymphocytes. This MCP-induced migration was dose-dependent and directional, but not chemokinetic. Phenotypic analysis of the T cell population responsive to MCP-1, MCP-2, and MCP-3 demonstrates that both CD4+ and CD8+ T cells migrated in response to these chemokines. Similar results were observed using human CD4+ and CD8+ T cell clones. Neutralizing antisera to MCAF or MCP-2 abrogated T cell migration in response to MCP-1 and MCP 2, respectively, but not to RANTES. Subcutaneous administration of purified MCP-1 into the hind flanks of SCID mice engrafted with human peripheral blood lymphocytes (PBL) induced significant human CD3+ T cell infiltration into the site of injection at 4 h. These results demonstrate that MCP-1, MCP-2, and MCP-3 are inflammatory mediators that specifically stimulate the directional migration of T cells as well as monocytes and may play an important role in immune cell recruitment into sites of antigenic challenge. PMID- 7883983 TI - Fluid shear stress induces endothelial transforming growth factor beta-1 transcription and production. Modulation by potassium channel blockade. AB - The endothelium has the capacity to modulate vascular structure in response to hemodynamic stimuli. We tested the hypothesis that exposure of the endothelium to increased laminar shear stress induces the expression of TGF beta 1 via a signal transduction pathway modulated by K+ channel currents. Although TGF beta 1 is normally secreted in a latent, inactive form, exposure of cultured endothelial cells to steady laminar shear stress (20 dynes/cm2) induced increased generation of biologically active TGF beta 1. This increase in active TGF beta 1 was associated with a sustained increase in TGF beta 1 mRNA expression within 2 h of stimulation. TGF beta 1 mRNA levels increased in direct proportion to the intensity of the shear stress within the physiologic range. The effect of shear stress on TGF beta 1 mRNA expression was regulated at the transcriptional level as defined by nuclear run-off studies and transient transfection of a TGF beta 1 promoter-reporter gene construct. Blockade of endothelial K+ channels with tetraethylammonium significantly inhibited: activation of TGF beta 1 gene transcription; increase in steady state mRNA levels; and generation of active TGF beta 1 in response to shear stress. These data suggest that endothelial K+ channels and autocrine-paracrine TGF beta 1 may be involved in the mechanotransduction mechanisms mediating flow-induced vascular remodeling. PMID- 7883985 TI - Subtype 2 of angiotensin II receptors controls pressure-natriuresis in rats. AB - Angiotensin II recognizes two receptor subtypes, AT1 and AT2, both of them having been recently cloned. Although AT2 receptors represent 5-10% of angiotensin II receptors in the kidneys of adult rats, their function remains unknown. In the present work, we examined the possible contribution of AT2 receptors to the regulation of pressure-natriuresis in anesthetized rats infused either with the specific AT2 antagonist PD 123319, or with CGP 42112B, an AT2 ligand with agonistic properties. The effects of PD 123319 were examined in a preparation with stable levels of angiotensin II, and in which AT1 receptors were blocked by the specific antagonist losartan. The effects of CGP 42112B were studied in rats deprived of endogenous angiotensin II. AT2 receptor blockade with PD 123319 did not change the renal blood flow while it increased the diuresis and natriuresis. These effects persisted even after full AT1 receptor blockade with losarfan. CGP 42112B did not modify the renal blood flow, but dose-dependently decreased urine flow and natriuresis. These results show that, contrary to AT1 receptors, renal AT2 receptors have no effect on total renal blood flow, but blunt the pressure natriuresis, thus demonstrating that this receptor subtype is involved in a function of importance for body fluid and blood pressure regulation. PMID- 7883986 TI - Induction of cross-reactive anti-dsDNA antibodies in preautoimmune NZB/NZW mice by immunization with bacterial DNA. AB - To investigate the role of antigen drive in anti-double-stranded (ds) DNA production, the antibody response induced in lupus-prone NZB/NZW mice by E. coli (EC) dsDNA was evaluated. Preautoimmune NZB/NZW female mice were immunized with complexes of EC dsDNA with methylated bovine serum albumin (mBSA) in complete Freund's adjuvant; control mice received either mBSA complexes with calf thymus (CT) dsDNA or mBSA alone in adjuvant. IgG antibody responses were assessed by ELISA. Similar to normal mice, immunized NZB/NZW mice produced significant levels of anti-dsDNA when measured with EC dsDNA as antigen. Whereas normal mice produce antibodies which are specific for the immunizing bacterial DNA, NZB/NZW mice produced antibodies that bound crossreactively to CT dsDNA by ELISA. Furthermore, the induced antibodies resembled lupus anti-DNA in their fine specificity for polynucleotide antigens and reactivity with Crithidia luciliae DNA. Despite their response to EC dsDNA, NZB/NZW mice immunized with CT dsDNA failed to generate significant anti-dsDNA responses. These results provide further evidence for the enhanced immunogenicity of bacterial DNA and suggest that immune cell abnormalities in NZB/NZW mice promote the generation of crossreactive autoantibody responses when confronted with a foreign DNA. PMID- 7883987 TI - The low density lipoprotein receptor is not required for normal catabolism of Lp(a) in humans. AB - Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein which is similar in structure to low density lipoproteins (LDL). The role of the LDL receptor in the catabolism of Lp(a) has been controversial. We therefore investigated the in vivo catabolism of Lp(a) and LDL in five unrelated patients with homozygous familial hypercholesterolemia (FH) who have little or no LDL receptor activity. Purified 125I-Lp(a) and 131I-LDL were simultaneously injected into the homozygous FH patients, their heterozygous FH parents when available, and control subjects. The disappearance of plasma radioactivity was followed over time. As expected, the fractional catabolic rates (FCR) of 131I-LDL were markedly decreased in the homozygous FH patients (mean LDL FCR 0.190 d-1) and somewhat decreased in the heterozygous FH parents (mean LDL FCR 0.294 d-1) compared with controls (mean LDL FCR 0.401 d-1). In contrast, the catabolism of 125I-Lp(a) was not significantly different in the homozygous FH patients (mean FCR 0.251 d-1), heterozygous FH parents (mean FCR 0.254 d-1), and control subjects (mean FCR 0.287 d-1). In summary, absence of a functional LDL receptor does not result in delayed catabolism of Lp(a), indicating that the LDL receptor is not a physiologically important route of Lp(a) catabolism in humans. PMID- 7883989 TI - Of mice and men: the mice were right. PMID- 7883988 TI - Abnormal contractile properties of muscle fibers expressing beta-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy. AB - Missense mutations in the beta-myosin heavy chain (beta-MHC) gene cause hypertrophic cardiomyopathy (HCM). As normal and mutant beta-MHCs are expressed in slow-twitch skeletal muscle of HCM patients, we compared the contractile properties of single slow-twitch muscle fibers from patients with three distinct beta-MHC gene mutations and normal controls. Fibers with the 741Gly-->Arg mutation (near the binding site of essential light chain) demonstrated decreased maximum velocity of shortening (39% of normal) and decreased isometric force generation (42% of normal). Fibers with the 403Arg-->Gln mutation (at the actin interface of myosin) showed lowered force/stiffness ratio (56% of normal) and depressed velocity of shortening (50% of normal). Both the 741Gly-->Arg and 403Arg-->Gln mutation-containing fibers displayed abnormal force-velocity relationships and reduced power output. Fibers with the 256Gly-->Glu mutation (end of ATP-binding pocket) had contractile properties that were indistinguishable from normal. Thus there is variability in the nature and extent of functional impairments in skeletal fibers containing different beta-MHC gene mutations, which may correlate with the severity and penetrance of the disease that results from each mutation. These functional alterations likely constitute the primary stimulus for the cardiac hypertrophy that is characteristic of this disease. PMID- 7883990 TI - The potential significance of beta 3 adrenergic receptors. PMID- 7883991 TI - RecA versus catalase: who's on first? PMID- 7883992 TI - Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts. Evidence for increased cell viability and suppression of cytokine release. AB - To elucidate cellular concepts for protection against ultraviolet (UV) light we investigated the effect of heat shock protein 70 (hsp70) overexpression on cell viability and on the secretion of UV-inducible immunological cytokines. Transfected murine fibrosarcoma cells (WEHI-S), overexpressing hsp70 or a sham transfected control were used. Overexpression of hsp70 was sufficient to markedly increase cell viability upon treatment with UVB (290-320 nm). Since long wave UV (UVA, 320-400 nm) as well as UVB turned out to stimulate the release of O2- radicals we studied the cell viability upon oxidative stress. Hsp70 overexpression increased viability upon treatment with hydrogen peroxide or menadione, but had no influence on UV-induced O2- release. UV-light is known to upregulate immunologic and proinflammatory cytokines such as IL-1 and IL-6. Oxidative stress appeared to exert a similar effect. Hsp70 overexpression markedly decreased the release of IL-6 induced by UVA, UVB and oxidative stress. To test whether the hsp70 mediated suppression is confined to events caused by UV light we determined IL-1-mediated effects. IL-1-induced IL-6 release was reduced by hsp70 overexpression, whereas the IL-1 mediated activation of nuclear factor kappa B was not affected. Our data suggests that hsp70 plays a central role not only in cell protection against UV-light, but also in the regulation of proinflammatory cytokine release induced by UV-exposure. PMID- 7883993 TI - Juvenile chronic arthritis: T cell reactivity to human HSP60 in patients with a favorable course of arthritis. AB - Synovial fluid and peripheral blood mononuclear cell proliferative responses to the 60-kD human heat shock protein (HSP60) were studied in 23 patients with juvenile chronic arthritis (JCA) and 7 non-JCA control patients. All patients showed active arthritis at the time of study. The patients were divided into two groups according to the presence (group A) or absence (group B) of T lymphocyte reactivity to human HSP60. We show that reactivity to human HSP60 is primarily, though not exclusively, occurring in patients with a remitting course of disease, i.e., the subgroup of HLA-B27 negative JCA patients with an oligoarticular onset. Immunohistochemical analysis of HSP expression in synovial membranes showed a significantly higher intensity of staining in JCA patients than in non-JCA controls. The results suggest that, in accordance with the earlier observation made in experimental models, T lymphocyte reactivity to human HSP60 in this subgroup of JCA patients may be part of T cell regulatory mechanisms that control the development of arthritis. PMID- 7883994 TI - A nonsense mutation 1669Glu-->Ter within the regulatory domain of human erythroid ankyrin leads to a selective deficiency of the major ankyrin isoform (band 2.1) and a phenotype of autosomal dominant hereditary spherocytosis. AB - We describe a nonsense mutation in the regulatory domain of erythroid ankyrin associated with autosomal dominant hereditary spherocytosis with a selective deficiency of the ankyrin isoform 2.1 (55% of normal), a deficiency of spectrin (58% of normal) proportional to the decrease in ankyrin 2.1, and a normal content of the other main ankyrin isoform, protein 2.2. PCR amplification of cDNA encoding the regulatory domain of ankyrin revealed a marked decreased in the ratio of ankyrin 2.1 mRNA to the ankyrin 2.2 mRNA. Sequencing of ankyrin gene in the region where the 2.1 and 2.2 mRNA differ detected a nonsense mutation 1669Glu ->Ter (GAA-->TAA) in one ankyrin allele. Only normal ankyrin 2.1 mRNA was detected in the reticulocyte RNA. Since the alternative splicing within the regulatory domain of ankyrin retains codon 1669 in ankyrin 2.1 mRNA and removes it from ankyrin 2.2 mRNA, we propose that the 1669Glu-->Ter mutation decreases the stability of the abnormal ankyrin 2.1 mRNA allele leading to a decreased synthesis of ankyrin 2.1 and a secondary deficiency of spectrin. PMID- 7883996 TI - Molecular and biochemical basis of intermediate maple syrup urine disease. Occurrence of homozygous G245R and F364C mutations at the E1 alpha locus of Hispanic-Mexican patients. AB - Maple syrup urine disease (MSUD) is caused by a deficiency of the mitochondrial branched-chain alpha-keta acid dehydrogenase (BCKAD) complex. The multienzyme complex comprises five enzyme components, including the E1 decarboxylase with a heterotetrameric (alpha 2 beta 2) structure. Four unrelated Hispanic-Mexican MSUD patients with the intermediate clinical phenotype were diagnosed 7 to 22 mo after birth during evaluation for developmental delay. Three of the four patients were found homozygous for G to A transition at base 895 (exon 7) of the E1 alpha locus, which changes Gly-245 to Arg (G245R) in that subunit. The remaining patient was homozygous for T to G transversion at base 1,253 in the E1 alpha gene, which converts Phe-364 to Cys (F364C) in the gene product. Transfection studies in E1 alpha-deficient lymphoblasts indicate that both G245R and F364C mutant E1 alpha subunits were unable to significantly reconstitute BCKAD activity. Western blotting showed that both mutant E1 alpha subunits in transfected cells failed to efficiently rescue the normal E1 beta through assembly. The putative assembly defect was confirmed by pulse-chase labeling of E1 subunits in a chaperone-augmented bacterial overexpression system. The kinetics of initial assembly of the G245R E1 alpha subunit with the normal E1 beta was shown to be slower than the normal E1 alpha. No detectable assembly of the F364C E1 alpha with normal E1 beta was observed during the 2 h chase. Small amounts of recombinant mutant E1 proteins were produced after 15 h induction with isopropyl thiogalactoside and exhibited very low or no E1 activity. Our study establishes that G245R and F364C mutations in the E1 alpha subunit disrupt both the E1 heterotetrameric assembly and function of the BCKAD complex. Moreover, the results suggest that the G245R mutant E1 alpha allele may be important in the Hispanic-Mexican population. PMID- 7883995 TI - The serum angiotensinogen concentration and variants of the angiotensinogen gene in white and black children. AB - The T235 allele of the angiotensinogen gene (AGT) has been associated with hypertension. Blood pressure increases faster over time in black children than in white children, and in adults hypertension is more prevalent in blacks. We sought evidence for a role for angiotensinogen to contribute to racial differences in blood pressure in a study of 148 white and 62 black normotensive children (mean age, 14.8 yr). The frequency of the T235 allele was 0.81 in blacks and 0.42 in whites (chi 2 = 77.3, P = 0.0001). The mean angiotensinogen level was 19% higher in blacks than in whites (P = 0.0001 for males, P = 0.004 for females). Genotype was positively related to serum angiotensinogen in white children (P = 0.0001 for males, P = 0.004 for females), but a similar relationship was absent in blacks where the frequency of M235 may have been too low to discern an association. Longitudinal blood pressure (measured twice yearly) adjusted for body mass index showed a marginally significant relationship to the angiotensinogen level (P = 0.07). An independent relationship of serum angiotensinogen with body mass index (P = 0.0001) and race (P = 0.0003) was also observed. In summary, T235 was more frequent, and the level of angiotensinogen was higher in blacks than in whites. Such a racial difference in the renin-angiotensin system may contribute to the disparity in blood pressure levels of white and black young people. PMID- 7883997 TI - Identification of malignant cells in multiple myeloma bone marrow with immunoglobulin VH gene probes by fluorescent in situ hybridization and flow cytometry. AB - Because it has been difficult to identify and separate malignant cells in human lymphoid malignancies, we have developed a flow cytometry-based fluorescent in situ hybridization (FISH) technique using immunoglobulin (Ig) heavy chain variable region (VH) gene probes. After obtaining the specific VH gene sequence expressed by the multiple myeloma IM-9 cell line and the malignant cells in five multiple myeloma patients, sense and antisense biotinylated single-stranded RNA probes were prepared by transcription from the malignant clone's VH DNA sequences. The cells from the IM-9 cell line and from the mononuclear bone marrow cells of multiple myeloma patients were fixed, hybridized with the above biotinylated RNA probes, incubated with streptavidin-phycoerythrin, and analyzed by FACS analysis. The myeloma cells stained positive with their own specific antisense VH biotinylated RNa probes, whereas sense and irrelevant antisense biotinylated probes demonstrated only background staining. Dilutional concentrations of the IM-9 cell line with normal bone marrow cells were also accurately quantitated by this procedure. The application of this technique will allow a more accurate assessment of tumor burden in patients with multiple myeloma and should permit an accurate method of tumor cell purification for clinical as well as biological studies. Furthermore, this technological advance should be equally effective at identifying specific VH gene-expressing cells in other lymphoid malignancies, as well as in nonmalignant B cell disorders. PMID- 7883999 TI - Metabolic predictors of obesity. Contribution of resting energy expenditure, thermic effect of food, and fuel utilization to four-year weight gain of post obese and never-obese women. AB - This prospective study was designed to identify abnormalities of energy expenditure and fuel utilization which distinguish post-obese women from never obese controls. 24 moderately obese, postmenopausal, nondiabetic women with a familial predisposition to obesity underwent assessments of body composition, fasting and postprandial energy expenditure, and fuel utilization in the obese state and after weight loss (mean 12.9 kg) to a post-obese, normal-weight state. The post-obese women were compared with 24 never-obese women of comparable age and body composition. Four years later, without intervention, body weight was reassessed in both groups. Results indicated that all parameters measured in the post-obese women were similar to the never-obese controls: mean resting energy expenditure, thermic effect of food, and fasting and postprandial substrate oxidation and insulin-glucose patterns. Four years later, post-obese women regained a mean of 10.9 kg while control subjects remained lean (mean gain 1.7 kg) (P < 0.001 between groups). Neither energy expenditure nor fuel oxidation correlated with 4-yr weight changes, whereas self-reported physical inactivity was associated with greater weight regain. The data suggest that weight gain in obesity-prone women may be due to maladaptive responses to the environment, such as physical inactivity or excess energy intake, rather than to reduced energy requirements. PMID- 7883998 TI - Posttranscriptional stabilization underlies p53-independent induction of p21WAF1/CIP1/SDI1 in differentiating human leukemic cells. AB - p21WAF/CIP1/SDI1 is a recently identified gene expressed in cells harboring wild type but not mutant p53 gene. It encodes a nuclear protein of 21 kD which inhibits cyclin-dependent kinase activity. Constitutive p21WAF1/CIP1/SDI1 mRNA expression was detected in neoplastic cells from patients with various hematological malignancies as well as in normal bone marrow mononuclear cells and in myeloid and lymphoid cell lines independent of their p53 status. Induced differentiation of the p53-deficient promyelocytic HL-60 cells along the monocytic lineage by phorbol ester or 1a,25 dihydroxyvitamin D3 resulted in a marked increase of both p21WAF1/CIP1/SDI1 mRNA and protein expression due to enhanced mRNA stability. Differentiation towards the granulocytic lineage by all trans retinoic acid or dimethylsulfoxide failed to produce this effect. p21WAF1/CIP1/SDI1 is an immediate early gene since its upregulation occurred independently of de novo protein synthesis. The induction of p21WAF1/CIP1/SDI1 expression and its regulation in p53-deficient differentiating leukemic cells support the idea of an additional, p53-independent role of p21WAF1/CIP1/SDI1 in human hematopoiesis. PMID- 7884000 TI - Transforming growth factor-beta reverses a posttranscriptional defect in elastin synthesis in a cutis laxa skin fibroblast strain. AB - Skin fibroblasts from two cases of autosomal recessive cutis laxa (CL), having insignificant elastin production and mRNA levels, were challenged with transforming growth factor beta-1 (TGF-beta 1). Elastin production was brought from undetectable values to amounts typical of normal human skin fibroblasts in a dose-dependent fashion. Basic fibroblast growth factor (100 ng/ml) alone or in combination with TGF-beta 1 reduced elastin production and mRNA expression in CL skin fibroblasts more extensively than in normal cells. In situ hybridization showed that these effects were at the transcript level. One of the CL strains was examined in detail. Transcription rates for elastin were similar in normal and CL and unchanged by TGF-beta 1 or TGF-beta 2 (10 ng/ml), while in CL elastin mRNA half-life was increased > 10-fold by TGF-beta 2 and reduced 6-fold after TGF-beta 2 withdrawal, as compared with a control strain. Cycloheximide partially reversed elastin mRNA instability. These data are consistent with a defect in elastin mRNA stability that requires synthesis of labile factors or intact translational machinery, resulting in an extremely low steady state level of mRNA present in this strain of CL. Furthermore, TGF-beta can relieve elastin mRNA instability in at least one CL strain and elastin production defects in both CL strains. PMID- 7884002 TI - Reinnervation of the trapezius muscle after radical neck dissection. AB - Based on the observation, that the caudal parts of the trapezius muscle after radical neck dissection with complete loss of the spinal accessory nerve, are still innervated to an individually varying degree, and on recent anatomical findings relating to this fact, a method for completely reinnervating the trapezius muscle, despite uncompromising radicality of the dissection, is introduced. This procedure consists of identifying and dislodging a subfascial branch of the deep cervical plexus running to the caudal parts of the trapezius muscle in the lateral cervical triangle and anastomosing it to the distal stump of the accessory nerve, using microsurgical techniques, thereby connecting it to the whole innervation system of the muscle. Clinical and electromyographical examinations showed very good recovery of all three portions of the muscle, 15 months after the procedure, in 46 of 52 patients (85%), although these patients were preselected by temporarily blocking the accessory nerve prior to operation, as possessing very little additional nerve supply. PMID- 7884001 TI - Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. A potential link between the renin-angiotensin system and thrombosis. AB - Plasminogen activator-inhibitor C-1 (PAI-1) plays a critical role in the regulation of fibrinolysis, serving as the primary inhibitor of tissue-type plasminogen activator. Elevated levels of PAI-1 are a risk factor for recurrent myocardial infarction, and locally increased PAI-1 expression has been described in atherosclerotic human arteries. Recent studies have shown that the administration of angiotensin converting enzyme inhibitors reduces the risk of recurrent myocardial infarction in selected patients. Since angiotensin II (Ang II) has been reported to induce PAI-1 production in cultured astrocytes, we have hypothesized that one mechanism that may contribute to the beneficial effect of angiotensin converting enzyme inhibitors is an effect on fibrinolytic balance. In the present study, we examined the interaction of Ang II with cultured bovine aortic endothelial cells (BAECs) and the effects of this peptide on the production of PAI-1. 125I-Ang II was found to bind to BAECs in a saturable and specific manner, with an apparent Kd of 1.4 nM and Bmax of 74 fmol per mg of protein. Exposure of BAECs to Ang II induced dose-dependent increases in PAI-1 antigen in the media and in PAI-1 mRNA levels. Induction of PAI-1 mRNA expression by Ang II was not inhibited by pretreating BAECs with either Dup 753 or [Sar1, Ile8]-Ang II, agents that are known to compete effectively for binding to the two major angiotensin receptor subtypes. These data indicate that Ang II regulates the expression of PAI-1 in cultured endothelial cells and that this response is mediated via a pharmacologically distinct form of the angiotensin receptor. PMID- 7884003 TI - Surgical management of the osteoradionecrotic mandible with free vascularised composite flaps. AB - Osteoradionecrosis (ORN) of the mandible is a serious sequel to radiotherapy administered for malignant neoplasms of the head and neck. In a retrospective/prospective study, 28 patients with mandibular defects due to ORN were reviewed. Monocortical and bicortical defects as well as pathological fractures were reconstructed by means of a free serratus anterior/rib (n = 8) or a vascularised iliac crest flap (n = 25). All the former survived; a pathological fracture, however, occurred postoperatively in 2 of the patients (25%). Five iliac crests were lost (20%). The remaining bone struts healed well. The donor site morbidity was very low. Clinical and radiological longterm follow-up showed that a very acceptable functional and cosmetic result was achieved in all cases. Progress of ORN was prevented in ca. 90% of all patients. The radiological follow up was facilitated with the use of high-resolution CT-scans. PMID- 7884004 TI - The use of mouldable acrylic for restoration of the temporalis flap donor site. AB - Despite the wide popularity of the pedicled temporalis myofascial flap, aesthetic management of the temporalis donor site has received little attention. A technique for immediate camouflage of the temporalis flap donor site with cold cure methyl methacrylate, either alone or in combination with residual muscle in the temporal fossa, is presented. A retrospective evaluation of this technique in 34 consecutive patients was undertaken, with particular reference to the aesthetic results and morbidity associated with the use of cold-cure acrylic for this form of reconstruction. Apart from transient postoperative swelling and neuropraxia, no major or lasting complications associated with the use of cold cure acrylic were recorded. The aesthetics of the camouflaged temporalis donor site by acrylic alone, or when combined with part of the temporalis muscle, was judged objectively to be excellent in 25 patients, satisfactory in 3 patients, and poor in 2 patients. 4 patients who did not have acrylic reconstruction, but had part of the temporalis muscle transposed to conceal the anterior fossa depression, leaving the posterior fossa unreconstructed, were judged mostly as satisfactory. Histology of the soft tissues around an acrylic implant after nearly 2 years confirmed the good biocompatibility of this material. It is concluded that this technique is a safe and reliable method for immediate camouflaging of the temporal fossa after harvesting a temporalis muscle flap. PMID- 7884005 TI - Reconstruction of facial soft tissues after resection of skin tumors. AB - The aim of the present study was to analyse the results of various reconstruction techniques of the facial skin with regard to general parameters such as the patients' age and health condition and to surgical parameters such as defect size, contamination of surgical fields and the type of reconstruction. 273 cases were evaluated, comprising local flaps (217), island flaps (21), free skin grafts (22) and cutaneous or myocutaneous distant flaps (13). The overall rate of major complications was 13.5%. No correlation was found with the age or impaired health of the patients nor did contamination by oral/nasal bacterial flora or the type of restoration show any significant correlation. The size of the defect turned out to be the only variable significantly related to the occurrence of complications (p = 0.0108). The complication rate observed following the repair of defects smaller than 30 mm in diameter was 7.5% while it rated 19.1% following the repair of defects larger than 30 mm. The overall rate of partial or total flap necrosis was low (2.9%). Secondary corrections and further surgical re-entry were required in 4.7% of all patients. PMID- 7884006 TI - Ameloblastic fibrosarcoma of the jaw: report of five cases. AB - Five cases of ameloblastic fibrosarcomas (AFS) are reported. The tumour was characterized histologically by a biphasic pattern: the malignant mesenchymal component had the features of an intermediate grade fibrosarcoma in 3 cases, malignant fibrous histiocytoma and osteogenic sarcoma in 2 cases. The epithelial odontogenic component had a benign appearance cytologically. In 1 patient, in the recurrence only the malignant mesenchymal component was present. AFS is a fully malignant tumour, in fact 1 patient died of the tumour after inadequate surgical treatments, and 2 patients had a recurrence after intralesional surgery. The treatment of choice was achieved when surgery with wide surgical margins was performed. As MFH and OGS features are present in the malignant mesenchymal component of this tumour we prefer to use the broad term ameloblastic sarcoma instead of AFS. PMID- 7884007 TI - Peripheral trigeminal nerve surgery for patients with atypical facial pain. AB - Atypical facial pain (AFP) is characterized by a constant, poorly defined anatomically aching pain, lacking the paroxysmal quality, trigger point activation, and well-defined anatomical distribution of trigeminal neuralgia. This study examines a set of AFP patients with respect to their responses to external decompression (4 patients) and neurectomy (11 patients). Criteria for trigeminal nerve exploration were: failure of non-operative treatments, the ability to control pain temporarily with local anesthetic nerve blocks, and pain generally located within the anatomical distribution of the affected nerve. Decision as whether to perform an external decompression or neurectomy was based on gross anatomical findings during exploration. A retrospective interview was conducted to evaluate the effects of the chosen procedure in regard to subjective level of pain, freedom from restrictions placed on activities of daily living, and past medical history, including history of the facial pain. The neurectomy procedure (p = 0.022), medical history of autoimmune disease (p = 0.004), and preoperative pain distribution on the left side (p = 0.042), were all found to have a positive effect on outcome. History of psychiatric treatment (p = 0.055) and preoperative affected activities of daily living (p = 0.026) significantly adversely affected the outcome. PMID- 7884008 TI - Changes in the temporomandibular joint caused by the vertical facial pattern. Study on an experimental model. AB - An experimental model reproducing open bite or verticalized facial pattern was used to study its effect on the temporomandibular joints. 140 Wistar rats were used, divided into 3 groups: bilateral resection of the masseteric muscle, simulated muscular resection and control group. A series of radiological, morphological and histological tests were analyzed. The posterior rotation of the jaw caused by muscular resection although not producing a degenerative effect, did produce specific articular changes in the temporomandibular joint components. PMID- 7884009 TI - Cephalometric alterations following facial advancement surgery. 2. Clinical and computerised evaluation. AB - Part 1 of this investigation identified an established patient cohort whose treatment is best suited to combined surgical-orthodontic correction of dento facial deformity. This is as opposed to the attempted correction of the problem by an orthodontics-only or a surgery-only approach. Experienced surgeons will subjectively assess facial aesthetics and devise surgical treatment objectives in terms of the beneficial soft tissue improvements derived from dento-skeletal manipulation. None the less, traditional and soft tissue cephalometric parameters remain a guideline in the diagnostic phase of treatment. Part 2 of this investigation compared pre and postoperative clinical and computerised evaluations of patients diagnosed as having combined mid and lower dento-facial deficiency with Class 1 dento-skeletal parameters. PMID- 7884010 TI - Comparison of injuries to children with and without disabilities in a day-care center. AB - Injury rates and characteristics of children with and without disabilities in separate day-care programs were studied retrospectively through a record review of injury logs. The study focused on three issues: (1) initial injury rates and multiple injury rates, with comparisons by gender and program; (2) the characteristics of children who were injured compared to those who were not injured; and (3) comparisons between programs on characteristics and consequences of injuries. Injury rates were calculated on the basis of children's exposure time in the day-care setting. Results showed that children with disabilities had higher rates of injury than those without disabilities. Injury prevention in day care should be tailored to the characteristics of children and the types of injuries that occur in this setting. PMID- 7884012 TI - Temperament and sleeping patterns in colicky infants during the first year of life. AB - A prospective study of 59 colicky infants and 58 age-matched controls assessed infants' temperament at the ages of 3 and 12 months and their sleeping patterns at the ages of 8 and 12 months. At age 3 months, the mothers regarded the colicky infants as more intense in their reactions, less persistent, more distractible, and more negative in their mood. At age 12 months, mothers regarded 23% of the colicky infants to be more difficult than average compared to 5% of controls. The mothers regarded their colicky infants as more active and less persistent. However, the Toddler Temperament Scale showed no difference between the groups in any area of temperament. No significant difference was found between the two groups in sleeping patterns. The discrepancy between infants' actual temperament and mothers' general perception of temperament may reflect the influence of infantile colic on the mother-infant relationship. PMID- 7884011 TI - Self-esteem of young adults with chronic health conditions: appraising the effects of perceived impact. AB - The relationships between selected condition characteristics and self-esteem were investigated in a randomly drawn, community-based sample of 286 young adults with chronic illnesses and disabilities. Whether appraisals of the impact of the condition mediated relationships between condition characteristics and self esteem, as measured by the Rosenberg Self-Esteem Scale, was also measured. As a group, the youth in this sample reported positive self-esteem. When sociodemographic and condition-related variables were considered simultaneously, maternal education, unpredictability of symptoms, prognosis, sensory impairment, and the presence of a co-occurring learning disability were found to have direct effects on esteem. Perceived impact mediated the relationship between condition characteristics and self-esteem. The results are discussed in relation to the role of impact appraisal in determining the emotional well-being of young adults with chronic illnesses. PMID- 7884014 TI - Is abuse during childhood a risk factor for developing substance abuse problems as an adult? AB - The purpose of this study was to evaluate the relationship between a history of childhood physical abuse and later substance abuse, controlling for family history of substance abuse. The study was a cross-sectional survey. Subjects were a convenience sample of mothers with children younger than 6 years being seen for routine care in five pediatric clinics. Mothers were given an anonymous, self administered questionnaire on demographics, substance abuse, history of physical abuse, and family history of substance abuse. Of the 733 respondents, 24% reported having been physically abused, 24% reported a family history of substance abuse, and 36% had a positive screen for substance abuse. A positive screen for substance abuse was more common among those who reported having been abused than those who had not (47% vs 32%, p < .001). After controlling for family history of substance abuse, a history of being abused remained significantly associated with current substance abuse (odds ratio = 1.58, 95% confidence interval 1.1, 2.2). Suffering abuse during childhood is a significant risk factor for later substance abuse, even after controlling for a family history of substance abuse. Clinicians treating victims of abuse may wish to include substance abuse prevention measures. PMID- 7884013 TI - Antineuronal antibodies: tics and obsessive-compulsive symptoms. AB - Fluorescent serum antibody determinations were used to examine whether children with obsessive-compulsive disorder (OCD) or less pervasive obsessive-compulsive symptoms (OCS) would show evidence of caudate nucleus involvement. Recent studies of OCD have documented smaller caudate nucleus volumes in adults with childhood onset than in normal controls, but not smaller putamen volumes. Thirty-eight cases were recruited from an ongoing study of childhood neurodevelopmental disorders. Nineteen samples from clinical cases had existing or previously documented OCS and attention-deficit hyperactivity disorder (ADHD) with or without concomitant tics. Nineteen additional clinical controls with ADHD, but without tics or OCS, were identified. The sera from clinical cases showed antibodies directed against caudate [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.0 to 4.1], putamen (OR 3.0; 95% CI 1.5 to 5.8), or both (OR 2.9; 95% CI 1.58 to 5.7) at a rate significantly higher than that of clinical controls, providing evidence of basal ganglia involvement in OCS. These preliminary data do not support a differential effect against caudate compared to putamen for these children, but suggest a more generalized central nervous system response. PMID- 7884015 TI - Behavioral and pharmacological treatments for tic and habit disorders: a review. AB - Children with tic and habit disorders are often seen by pediatricians, psychologists, or psychiatrists for evaluation and treatment. Current knowledge of the treatment-outcome research in these areas can serve as an important guide in the evaluation and treatment planning process. This article reviews the behavior therapy and pharmacological treatment of motor and vocal tic disorders, self-destructive oral habits, trichotillomania (hair pulling), onychophagia (nail biting), and thumb sucking. The research evidence indicates that all of these disorders can be effectively treated with behavioral or pharmacological approaches. PMID- 7884016 TI - Fluoxetine inhibition of phenytoin metabolism. PMID- 7884017 TI - A double-blind controlled study of intramuscular zuclopenthixol acetate and liquid oral haloperidol in the treatment of schizophrenic patients with acute exacerbation. AB - We carried out a 9-day double-blind clinical trial comparing intramuscular zuclopenthixol acetate with liquid oral haloperidol in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation. A parallel-group design was used with stratification by sex. Zuclopenthixol acetate (50 to 150 mg) was given intramuscularly every 3 days, whereas liquid haloperidol (10 to 30 mg daily) was given orally three times a day, with supplementary doses of each medication given under double-blind conditions when needed for agitation. No other sedative drugs, including benzodiazepines, were administered. The mean daily dose was 18.9 mg for haloperidol as compared with a mean dose per 3 days of 117.6 mg for zuclopenthixol. The two treatments were found to be equally efficacious on the Brief Psychiatric Rating Scale and Clinical Global Impression Scale. Both drugs induced similar extrapyramidal side effects. However, more tremors were associated with zuclopenthixol as was a tendency for tardive dyskinesia to be unmasked at the end of the injection interval. Sedation was higher with zuclopenthixol acetate than with haloperidol. Serum creatinine phosphokinase levels were not significantly increased after zuclopenthixol injections. The results of this trial suggest that zuclopenthixol acetate given intramuscularly every second to third day offers an alternative to conventional liquid oral haloperidol in the management of acute schizophrenia. PMID- 7884018 TI - Is baseline agitation a relative contraindication for a selective serotonin reuptake inhibitor: a comparative trial of fluoxetine versus imipramine. AB - A common presentation for major depression includes psychomotor agitation. However, this subtype has been the infrequent subject of controlled investigation during depression trials. Yet, the subcategorization of agitated depression has historically been associated with the belief that older, sedating compounds have a superior risk:benefit profile. In the 8-week, double-blind, randomized, parallel trial, 124 subjects with Research Diagnostic Criteria-compatible agitated depression were randomized to either imipramine (IMI) or fluoxetine (FLU). Both compounds proved to be similarly effective as measured by change in HAM-D17, HAM-D17 response, and HAM-D17 remission rates. Similar comparability was seen in secondary measures of agitation, anxiety, suicidality, and global impressions. However, of note, a statistically significant difference in early discontinuations because of intolerable adverse events emerged. Whereas 43.5% of IMI subjects discontinued early, only 9.7% of FLU subjects (p < 0.001) did. Significantly more central nervous system events characterized the IMI than the FLU subgroup (IMI, 24.2%, vs. FLU, 6.5%; p = 0.006). In conclusion, among subjects with major depression, subtype agitated, the risk:benefit profile favored FLU over IMI. This was driven by the superior tolerance of FLU. No evidence emerged in support of the clinical hypothesis that a "sedating" agent is the treatment of choice for this group. The results are important when striving to maximize compliance with pharmacotherapy in order to minimize recidivism and associated psychological and economic morbidity. PMID- 7884019 TI - The effect of amitriptyline, doxepin, fluvoxamine, and paroxetine treatment on heart rate variability. AB - A total of 32 unmedicated patients with episodes of major depression (DSM-III-R) and 32 normal control subjects matched for age and sex were tested for heart rate variability (R-R variation) while resting and during deep breathing. Compared with the group of healthy subjects, the depressed patients showed no abnormalities before therapy. The patients were randomly allocated for treatment with 150 mg of amitriptyline per day (N = 8), 150 mg of doxepin per day (N = 8), 150 mg of fluvoxamine per day (N = 8), and 20 mg of paroxetine per day (N = 8). During treatment with either amitriptyline or doxepin, the coefficients of variation at rest and during deep breathing, which are largely independent of heart rate, had significantly decreased after 14 days (p = 0.012), whereas patients treated with fluvoxamine or paroxetine showed no significant changes of heart rate variability parameters after 14 days. The implications of these findings are discussed. PMID- 7884020 TI - Fluoxetine alters the effects of intravenous cocaine in humans. AB - Fluoxetine, a selective serotonin reuptake inhibitor, is currently being evaluated as a potential treatment for cocaine abuse. This 4-week inpatient study evaluated the pharmacologic interaction between fluoxetine and cocaine in healthy adult male volunteers (N = 5) with histories of cocaine abuse. Oral capsules were administered daily containing either placebo (weeks 1 and 4) or fluoxetine in a series of ascending doses (10, 20, 30, and 40 mg) where each dose was given for three to four consecutive days. Cocaine challenge sessions were conducted twice weekly, once at each active dose level and twice during both the placebo and washout phases. Subjects received three ascending intravenous doses of cocaine (0, 20, and 40 mg) 1.5 hours apart and were monitored on physiologic and subjective measures. Cocaine alone increased heart rate, blood pressure, and pupillary diameter and increased subjective reports reflecting positive mood effects and drug liking. Fluoxetine (40 mg) significantly decreased subjective ratings of cocaine's positive mood effects on several visual analog measures. Fluoxetine also attenuated the mydriatic effect of cocaine. No adverse physiologic interactions between the two drugs were observed on cardiovascular measures. These data suggest that fluoxetine may be safely used in the presence of cocaine use and should be investigated further as a potential pharmacotherapy for cocaine abuse. PMID- 7884021 TI - Rash complicating carbamazepine treatment. AB - Carbamazepine--widely used in the treatment of trigeminal neuralgia, seizure disorders, and more recently, manic-depressive illness--is generally safe and well tolerated. Although serious adverse reactions, such as hematologic toxicity, may occur rarely, we have found that carbamazepine-induced rash is common, occurring in 13 (12%) of 113 patients. We describe our experience with carbamazepine-induced rash, including clinical characteristics, demographic features, and associated laboratory findings. Integrating our findings with the literature, we also discuss incidence, possible mechanisms, and implications for treatment because these benign rashes can occasionally progress to more fulminant and life-threatening eruptions. PMID- 7884022 TI - Pharmacologic effect of toloxatone on reactivity to the 35% carbon dioxide challenge: a single-blind, random, placebo-controlled study. AB - The effect of a short treatment (7 days) with the reversible monoamine oxidase type A inhibitor toloxatone on the reactivity to the inhalation of 35% CO2 was evaluated in 18 panic patients who responded to 35% CO2 inhalation with panic before treatment. A single-blind, placebo-controlled design was applied. Panic patients were randomly assigned to the toloxatone (N = 10) or placebo (N = 8) groups and were given the 35% CO2 challenge on days 1 (before starting the treatment), 3, and 7. Patients on placebo did not report any significant changes in their reactivity to 35% CO2 during the three sessions, whereas patients on toloxatone reported a significant attenuation of the reactivity on day 7. These results indicate that (1) anxiety provoked by the inhalation of 35% CO2 is reproducible; (2) placebo has a negligible effect on 35% CO2 reactivity; and (3) reactivity to 35% CO2 is significantly attenuated by short treatment with toloxatone, possibly related to its antipanic activity. PMID- 7884024 TI - Cyproheptadine in treatment-resistant chronic schizophrenics with prior negative response to fluoxetine. PMID- 7884023 TI - Venlafaxine for treatment-resistant unipolar depression. AB - The purpose of this study is to evaluate the novel antidepressant venlafaxine for the management of treatment-resistant unipolar depression. We gave unblinded venlafaxine to 84 consecutive outpatients and inpatients who met DSM-III-R criteria for major depression and who had failed to respond to at least three adequate trials of antidepressants from at least two different antidepressant classes or electroconvulsive therapy, plus at least one attempt at augmentation. Patients were evaluated after a drug free period at baseline and regular intervals with the 21-item Hamilton Rating Scale for Depression (HAM-D-21), Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions Scale Improvement item (CGI). Full response for each scale was defined as follows: HAM-D-21 score of 8 or lower, a MADRS score of 12 or lower, and CGI score of 1; partial responses was defined as a 50% decrease in the HAM-D and MADRS, with final scores greater than 8 and 12, respectively, and for the CGI, a score equal to 2. About a third of patients were considered to be either full or partial responders (32.9% by HAM-D-21, 30.0% by MADRS, and 40% by CGI) after 12 weeks of venlafaxine treatment. To date, about 46% of responders have sustained their response for at least 3 months after the acute response. Venlafaxine is effective for a significant, but small, minority of patients with rigorously defined triple-resistant depression; the improvement was maintained for about half of the responders for the first 3 months of maintenance therapy. PMID- 7884025 TI - Clozapine rechallenge after marked liver enzyme elevation. PMID- 7884026 TI - Seizures in two patients after the addition of lithium to a clozapine regimen. PMID- 7884027 TI - Unsuccessful reexposure to clozapine. PMID- 7884028 TI - Syncope associated with the combination of clozapine and enalapril. PMID- 7884029 TI - Sertraline and speech blockage. PMID- 7884030 TI - Fluoxetine-associated panic attacks. PMID- 7884031 TI - Priapism with sertraline and lithium. PMID- 7884032 TI - Lithium-induced renal dysfunction. PMID- 7884033 TI - Case 2: Dizzy Giuseppi or the vertiginous virtuoso. PMID- 7884034 TI - Is there anything new on the use of psychotropic drugs during pregnancy? PMID- 7884035 TI - Fine structure of rat septohippocampal neurons. III. Recovery of choline acetyltransferase immunoreactivity after fimbria-fornix transection. AB - Most cholinergic projection neurons in the medial septal nucleus (MS) lose their capability to synthesize choline acetyltransferase (ChAT) after axotomy by bilateral fimbria-fornix transection. We have recently shown that identified septohippocampal neurons survive axotomy up to 10 weeks and display fine structural characteristics of cells in control rats. However, the fate and functional role of these neurons remained unclear. Here we describe observations made in rats which survived axotomy for 6 months. Adult Sprague-Dawley rats were subjected to bilateral transection of the fimbria-fornix system. In some animals septohippocampal projection neurons were labeled by the retrograde fluorescent tracer Fluoro-Gold (FG) prior to axotomy. After varying survival times following fimbria-fornix transection, the animals were fixed and sections of the septal region immunostained for ChAT. Three weeks postlesion, the number of ChAT positive cells in the MS was reduced to 19% of control, suggesting a severe neuronal loss. However, 10 weeks and 6 months after axotomy this value increased to 28% and 54%, respectively. Fine-structural analysis of ChAT-positive neurons after 6 months survival revealed all characteristics of vital cells including normal input synapses. The majority of these cells could be identified as former septohippocampal projection neurons by the presence of FG. We conclude that many neurons in the MS have the capacity to restore their transmitter synthesis in a long-lasting process following axotomy. PMID- 7884037 TI - Postnatal development of the hamster cochlea. II. Growth and differentiation of stereocilia bundles. AB - The postnatal development of stereocilia was studied in the Syrian golden hamster. The purpose was to describe the morphological changes underlying the differentiation of stereocilia bundles and to define the time course of their growth in different regions of the cochlea. Differentiation of the hair bundle occurred by progressive changes in stereocilia number, dimensions, and spatial relationships. The overall transformation of the bundle is interpreted as a four stage process involving the initial production of stereocilia (stage I), differentiation into tall and short populations (stage II), formation of distinct ranks (stage III), and resorption of excess stereocilia (stage IV). The orientation and arrangement of stereocilia during stage II began to occur before the tectorial membrane grew over the hair cell field. Growth in the dimensions of stereocilia occurred continuously throughout these four stages with increases in length and width occurring simultaneously. The time frame of the growth process depended both on location along the organ of Corti and on the type of hair cell. Hair bundles in the basal turn began growing and reached maturity a few days earlier than those in the apical turn. Stereocilia of outer hair cells matured earlier than those of inner hair cells. Outer hair cell stereocilia reached their adult lengths by 14 days after birth, those of inner hair cells between 16 and 18 days after birth. A kinocilium was present on almost all hair cells on the day of birth, but most were eliminated by 14 days after birth. Tip links were observed as early as 4 days after birth, and their growth appeared to be synchronous with the growth of stereocilia. The spatial gradient of stereocilia length, which increased toward the apex in the adult, was nearly the reverse of that seen at birth. The gradient for inner hair cells was associated with a gradient in the rate of stereocilia growth. The data further expand the foundation for interpreting mechanisms underlying the morphogenesis of stereocilia bundles in mammals and for understanding structure-function relationships during development. PMID- 7884036 TI - Microglia in the avian retina: immunocytochemical demonstration in the adult quail. AB - Immunocytochemical techniques were used in conjunction with the QH1 antibody to study the morphological characteristics and distribution of microglia in the avascular retina of an avian species (the quail). The majority of microglial cells appeared in the outer and inner plexiform layers throughout the entire retina, whereas a few microglial cells in the nerve fiber layer were seen only in the central zone of the retina, near the optic nerve head. In the outer plexiform layer, microglial cells were star-shaped, with processes that ramified profusely in the horizontal plane. Fine process tips extended outward radially, insinuating themselves among the photoreceptors. A regular mosaic-like arrangement of microglial cells was evident in the outer plexiform layer, with no overlapping between adjacent cell territories. Microglial cells in the inner plexiform layer ramified through the entire width of this layer, showing radial and horizontal processes. Microglia in the inner plexiform layer also tended to be regularly distributed in a mosaic-like fashion, although there was slight overlapping between adjacent cell territories. Microglia density in this layer was approximately twice that in the outer plexiform layer. This pattern of microglial distribution was similar to that described in vascular retinae of several species of mammals, a finding that suggest that blood vessels are not responsible for the final locations of microglia in the adult retina, and that microglial precursors must migrate through long distances before they reach their precise destination. PMID- 7884038 TI - Central processing of sex pheromone, host odour, and oviposition deterrent information by interneurons in the antennal lobe of female Spodoptera littoralis (Lepidoptera: Noctuidae). AB - Physiological and anatomical characteristics of antennal lobe interneurons in female Spodoptera littoralis (Boisd.) were investigated using intracellular recording and staining techniques. Responses of local interneurons and projection neurons to female sex pheromone components, host plant odours, and behaviourally active oviposition deterrents were recorded. We found local interneurons and projection neurons that responded specifically to only one or two of the tested odours, but we also found less specific cells, and neurons that responded to most of the tested odourants. These findings show that there are not only specific olfactory pathways in female moths up to the protocerebral level, but also that integration can begin in the antennal lobe. No correlation was found between the degree of specificity of either local interneurons or projection neurons and their respective morphological characteristics. Specialized and unspecialized local interneurons arborized throughout the antennal lobe. Specialized and unspecialized projection neurons had uniglomerular arborizations in the antennal lobe and sent their axons to the calyces of the mushroom body, and to the lateral horn of the protocerebrum. One specific projection neuron had multiglomerular arborizations and projected only to the lateral horn of the protocerebrum. Projection neurons arborizing in the glomeruli closest to the entrance of the antennal nerve always responded to pheromone components. No other correlations were found between the arborization pattern of projection neurons in the antennal lobe or in the protocerebrum and their response characteristics. The sensitivity of local interneurons and projection neurons was in the same range as that of receptor neurons in olfactory sensilla on the antennae, suggesting a much lower convergence in the central nervous system in females than in the pheromone processing pathway in males. PMID- 7884039 TI - Rearing with monocular lid suture induces abnormal NADPH-diaphorase staining in the lateral geniculate nucleus of cats. AB - We investigated the changes in NADPH-diaphorase staining that occur in the lateral geniculate nucleus of cats following rearing with monocular lid suture. This staining allows visualization of the synthesizing enzyme of nitric oxide, a neuromodulator associated with plasticity. In the lateral geniculate nucleus of normally reared cats, NADPH-diaphorase exclusively labels the axons and terminals of an input from the parabrachial region of the brainstem; no geniculate cells in the A-laminae are labeled. Early monocular lid suture has no obvious effect on the NADPH-diaphorase staining of parabrachial axons. However, this lid suture results in the abnormal appearance of NADPH-diaphorase staining for geniculate somata. These cells are located primarily in the nondeprived laminae. Double labeling experiments indicate that these cells with abnormal NADPH-diaphorase reactivity are Y relay cells: NADPH-diaphorase staining is found in cells retrogradely labeled from visual cortex; it is found in cells labeled with a monoclonal antibody for CAT-301, which selectively targets Y cells; it is not found in cells labeled with an anti-GABA antibody, which targets interneurons. Also, NADPH-diaphorase labeled cells are among the largest cells in the nondeprived laminae, again suggesting that they are Y relay cells. We cannot suggest a specific mechanism for this induction of NADPH-diaphorase labeling, but it does not seem to be due to abnormal binocular competition induced by the monocular lid suture. PMID- 7884040 TI - Immunocytochemical expression of the blood-brain barrier glucose transporter (GLUT-1) in neural transplants and brain wounds. AB - The present study examined the immunocytochemical expression of the blood-brain barrier glucose transporter (GLUT-1) in a series of fetal neocortical transplants, autonomic tissue transplants, and stab wounds to the rat brain. GLUT 1 is one of a family of different glucose transporters and is found exclusively on barrier-type endothelial cells. In the brain it is responsible for the regulated facilitative diffusion of glucose across the blood-brain barrier. This investigation is the first to determine if this important molecule is altered during the process of angiogenesis that occurs following neural transplantation procedures or direct brain injury. Beginning in late fetal brain, e.g., E18 and continuing into maturity, GLUT-1 was strongly and exclusively expressed on normal cerebral vessels. In solid fetal central nervous system (CNS) transplants up to around 3 weeks postoperative, GLUT-1 was only weakly expressed, particularly as exemplified by colloidal gold immunostaining when compared with the host. At later times examined, up to 15 months postoperative, GLUT-1 immunoexpression was comparable with the normal adjacent brain. In autonomic tissue transplants, where the vessels do not have a blood-brain barrier, as expected, GLUT-1 was not expressed. In stab wounds, at 1 week there was extensive gliosis, and the injured vessels appeared fragmented and collapsed but still expressed GLUT-1, although to a somewhat lesser extent than normal brain. Between 3 and 6 weeks, GLUT-1 was expressed on tortuous vessels and in apparently fibrillar processes in the wound vicinity with a similar pattern to astrocyte (GFAP) reactivity. These results suggest the occurrence of a down-regulation of GLUT-1 in early transplants, perhaps related to reduced glycolytic activity or transient ischemia, or possibly due to the utilization of alternative energy sources. That GLUT-1 expression was not entirely lost in stab wounds to the mature brain suggests that the protein may be more labile in fetal or perinatal brain than in the adult and may not be affected by direct injury. Coupled with previous transplantation studies that have shown reduced neuronal glycolysis and potential barrier alterations, the reduction of GLUT-1 activity within nearly the identical time frame could indicate a relatively early critical period in cellular metabolism following transplantation of CNS tissue. PMID- 7884041 TI - Cellular localization and laminar distribution of AMPA glutamate receptor subunits mRNAs and proteins in the rat cerebral cortex. AB - The cellular and laminar distributions of the alpha-amino-3-hydroxy-5- methyl-4 isoxazole propionate (AMPA) receptor subunits GluR1-4 have been investigated in the cerebral cortex of adult rats by in situ hybridization with 35S-labeled cRNA probes and by immunocytochemistry with subunit-specific antibodies. In sections incubated with the GluR1-4 antisense probes, specific hybridization signal was observed in many but not all cortical cells. Experiments with in situ hybridization and antibodies to glial fibrillary acidic protein (GFAP) showed that percentages of GFAP-immunoreactive cells labeled by the GluR1-4 probes were 20%, 9.4%, 8.2%, and 57.3%, respectively. A semiquantitative evaluation revealed that about 56% of cortical neurons contained the GluR1 subunit, 80% the GluR2, 63% the GluR3, and 44% the GluR4. The number of grains associated with every neuron was determined from sections exposed for 15 days, the background level was subtracted, and labeled neurons were divided into four groups: A (< or = 10 grains), B (11-20 grains), C (21-30 grains), and D (> 30 grains). The number of neurons belonging to each of these groups was then evaluated for their occurrence in each cortical layer. Immunocytochemistry with subunit-specific antibodies showed that 1) GluR1-immunoreactive neurons were mostly layers V and VI nonpyramidal neurons; 2) GluR2/3-immunoreactive neurons were more numerous in layers II-III and V-VI, and most of them were pyramidal; and 3) GluR4-positive cells were the least numerous, and they were either neurons (pyramidal and nonpyramidal) or astrocytes. These observations indicate that cortical neurons exhibit a remarkable degree of heterogeneity with regard to both the composition and the number of AMPA receptors and suggest that this diversity might be correlated with the functional attributes of neurons receiving glutamatergic afferents and with the physiological features of corticifugal neurons. PMID- 7884042 TI - Immunocytochemical localization of the beta 2 subunit of the gamma-aminobutyric acidA receptor in the rat brain. AB - An antiserum to the beta 2 subunit of the rat gamma-aminobutyric acid (GABAA) receptor was prepared by immunizing a rabbit with a fusion protein expressed in bacteria. The fusion protein had the large, intracellular loop expanding between the putative M3 and M4 transmembrane domains of the beta 2 subunit fused to staphylococcal protein A (SPA). The antiserum immunoprecipitated both the solubilized and the affinity-purified GABAA receptors. The anti-beta 2 antibodies were affinity purified on immobilized beta 2 intracellular loop peptide. The antibodies recognized a 55-57 kDa peptide in immunoblots of either crude membranes from rat cerebral cortex or affinity-purified GABAA receptors from bovine cerebral cortex. Immunocytochemistry with the affinity-purified antibody has revealed for the first time the localization of the beta 2 subunit in the rat brain. A comparative study of the regional and cellular immunoreactivities of the affinity-purified anti-beta 2 antibody and the monoclonal antibody 62-3G1 (which recognizes both beta 2 and beta 3 subunits) is presented. The procedure described for generating and preparing specific anti-beta 2 subunit antibodies that are valuable for immunocytochemistry could be extended to other GABAA receptor subunits. PMID- 7884043 TI - Two types of interneuron in the dorsal lateral geniculate nucleus of the rat: a combined NADPH diaphorase histochemical and GABA immunocytochemical study. AB - The rationale for this study was to provide a comprehensive light microscopical description of the morphology of diaphorase-reactive neurons and neuropil elements in the dorsal lateral geniculate nucleus (dLGN) of the rat. An additional objective was to quantitatively assess whether a subpopulation of the diaphorase-reactive neurons, previously shown to be GABA-immunoreactive, constitute a distinct type of local-circuit neuron in the rat dLGN. Diaphorase activity was localised in a population of predominantly bipolar fusiform neurons. These cells were weak to moderately stained and possessed the morphological features of intrinsic inhibitory neurons, previously called class B neurons in the rat dLGN. Quantitative estimates indicated that the diaphorase-reactive neurons constituted approximately 10% of the total neuron composition of the dLGN. The majority (about 83%) of the diaphorase-reactive cells were located in the lateral half of the nucleus. In addition, a dense plexus of diaphorase reactive varicose fibres was found throughout the dLGN lying between the oriented fibre bundles coursing dorsoventrally through the LGN. Diaphorase-reactive punctae were found to be closely associated with the somata and proximal dendritic segments of nonreactive neurons and also with the stained proximal dendritic segments of diaphorase-reactive dLGN neurons. The source of the diaphorase-reactive fibres in the dLGN was unknown. Evidence suggests, however, that they are of extrinsic origin. The GABA-immunoreactive nature of the diaphorase neurons in the dLGN was demonstrated by colocalising GABA immunoreactivity within the somata of diaphorase-reactive cells. The majority (> 90%) of diaphorase-reactive dLGN neurons were GABA-immunopositive. Also present was a distinct population of GABA-immunopositive neurons that were not diaphorase reactive. In this study, cells that were solely GABA-immunopositive have been called class B1 neurons, while cells that were both diaphorase-reactive and GABA immunoreactive have been called class B2 neurons. Size-frequency distributions of somatic profile areas established that the two populations of GABA-immunoreactive neuron were significantly different. Class B1 neurons constituted 57%, with class B2 cells representing 43% of all GABA-immunostained neurons in the rat dLGN. The characteristic morphological features, neurochemical identity and frequency of the diaphorase-reactive neurons in the rat dLGN indicate that they represent a subpopulation of inhibitory interneurons with the ability to affect intrinsic dLGN operations and thalamocortical interactions using the neuromodulator nitric oxide. PMID- 7884044 TI - Cytochemical characteristics of neurons in the trigeminal mesencephalic nucleus of hatchling chicks. AB - The goal of the present study was to identify cytochemical markers characteristic of muscle afferents in hatchling chicks. To this end, we stained neurons in the trigeminal mesencephalic nucleus with a variety of markers that label subsets of neurons in avian dorsal root ganglia. We found that trigeminal mesencephalic neurons are surprisingly heterogeneous in their cytochemical make-up, expressing, to varying degrees, substance P, cholecystokinin, carbonic anhydrase, calbindin D 28k, parvalbumin, and S-100 beta. Calbindin D28k and S-100 beta appeared to be expressed equally in medial and lateral divisions of the trigeminal mesencephalic nucleus. In contrast, substance P- and cholecystokinin-immunoreactive neurons were more abundant in the medial division, whereas carbonic anhydrase activity and parvalbumin immunoreactivity were stronger in the lateral division. We were unable to detect met-enkephalin, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal peptide, somatostatin, gamma-aminobutyric acid, or tyrosine hydroxylase in the trigeminal mesencephalic nucleus. Moreover, these neurons did not appear to bind the lectin Dolichos biflorus agglutinin. The heterogeneity of expression of markers among trigeminal mesencephalic nucleus neurons, especially between neurons in the medial and lateral divisions, suggests that these neurons are functionally diverse. PMID- 7884045 TI - Distribution of thyrotropin-releasing hormone (TRH)-containing cells and fibers in the human hypothalamus. AB - In the present study, we describe for the first time the distribution of thyrotropin-releasing hormone (TRH)-containing cells and fibers in the human hypothalamus using brain material obtained with a short postmortem delay. Following fixation in paraformaldehyde, glutaraldehyde and picric acid, excellent staining was obtained with two different TRH antisera. Many TRH-containing neurons were present in the paraventricular nucleus (PVN), especially in the dorsocaudal part of this nucleus. They were mostly parvicellular, but a few magnocellular TRH-positive neurons were observed as well. The PVN also contained a dense network of TRH fibers. The supraoptic nucleus (SON) did not show any TRH immunoreactivity, excluding the possibility of cross-reactivity of the antiserum with neurohypophysial hormones or their precursors. In addition, TRH cells were found in the suprachiasmatic nucleus (SCN), which is the circadian clock of the brain, in the sexually dimorphic nucleus (SDN) and dorsomedially of the SON. We observed small number of TRH cells throughout the hypothalamic gray in all subjects studied. A high density of TRH-containing fibers was seen not only in the median eminence but also in other hypothalamic areas, e.g., in the ventromedial nucleus (VM) and in the perifornical area. The results generally agree with earlier data in the rat, with the exception of the absence of TRH cells in the SON. The large number of sites of TRH-containing fiber terminations on neurons suggests important physiological functions of this neuropeptide as a neurotransmitter or neuromodulator in the human brain, in addition to its role as a neurohormone in pituitary secretion of thyroid-stimulating hormone (TSH). PMID- 7884046 TI - Parvalbumin-containing GABAergic neurons in the basal ganglia output system of the rat. AB - The output of the basal ganglia is directed through the entopeduncular nucleus (EPN) and the substantia nigra pars reticulata (SNR) and pars lateralis (SNL), which provide a gamma-aminobutyric acidergic (GABAergic) projection to various nuclei of the thalamus and brainstem. Although many neurons within the SNR and EPN have been described as modality specific, the morphological and neurochemical similarities preclude their precise identification. In the present study, the immunocytochemical localization of parvalbumin, a calcium-binding protein, is used in combination with axonal tracing to verify neuronal heterogeneity within the SNR, SNL, and EPN. The results reveal that the majority of neurons in all three centers contain parvalbumin. The parvalbumin-containing neurons are distributed in the caudal two-thirds of the EPN, the rostral part of the SNL, and the lateral two-thirds of the entire rostrocaudal extent of the SNR, the areas involved in sensorimotor function of the basal ganglia. Moreover, the nigrothalamic, nigrocollicular, and EPN-thalamic neurons possess parvalbumin immunoreactivity, whereas the EPN-habenular neurons are devoid of parvalbumin immunoreactivity. The results indicate a neurochemical heterogeneity within the GABAergic output neurons of the basal ganglia and suggest that the parvalbumin containing neurons of the SNR, SNL, and EPN are the tonically active output neurons that form a major link in the disinhibitory neuronal circuit of the basal ganglia, especially that concerned with sensorimotor function. PMID- 7884047 TI - Embryonic development of the stomatogastric nervous system in Drosophila. AB - Using several cell-specific markers, the pattern of proliferation, morphogenesis, and neuronal differentiation of the Drosophila larval stomatogastric nervous system (SNS) was analyzed. In the late embryo, four SNS ganglia (frontal ganglion, hypocerebral ganglion, paraesophageal ganglion, ventricular ganglion) can be distinguished. In the early embryo, the precursor cells of the SNS (SNSPs), being an integral part of the anlage of the esophagus, undergo four synchronous rounds of division. Subsequently, SNSPs segregate from the esophageal epithelium in a complex and stereotyped pattern. The majority of SNSPs invaginate and transiently form three (rostral, intermediate, caudal) pouches that, after separating from the esophagus, become epithelial vesicles. At later stages, these SNSPs gradually lose their epithelial phenotype. Starting at the anterior-dorsal tip of each vesicle, SNSPs dissociate from one another and migrate to the various locations where they differentiate as neurons. Cells of the rostral and intermediate vesicle contribute to the frontal ganglion; the hypocerebral ganglion develops from the intermediate vesicle, the paraesophageal ganglion from the rostral vesicle, and the ventricular ganglion from the caudal vesicle. In addition to the invaginating SNSPs, several distinct groups of SNSPs delaminate as individual cells from the esophageal epithelium. Three clusters of SNSPs delaminate from a region anterior to the rostral pouch; a single SNSP delaminates from the tip of each pouch. All delaminating SNSPs contribute to the frontal ganglion. A significant number of SNSPs undergo cell death. In the late embryo, the stomatogastric ganglia are interconnected by the recurrent nerve and esophageal nerves. The frontal ganglion projects to the brain via the frontal connectives. Both recurrent nerve and frontal connectives are pioneered by small subpopulations of early differentiating stomatogastric neurons that most likely derive from among the dSNSPs and iSNSPs. PMID- 7884048 TI - Distribution of beta-endorphin-like-immunoreactive structures in the chicken and quail brain as demonstrated with a new homologous antibody directed against a synthetic peptide. AB - A polyclonal rabbit antibody was raised against a synthetic peptide fragment located at the C-terminal end of turkey beta-endorphin (beta-END) and used to analyze the distribution of beta-END-immunoreactive-like structures in the quail and chicken brain. Three major groups of immunopositive cells were detected in the preoptic area-hypothalamus complex. A thin layer of immunopositive cells was parallel and adjacent to the ventral edge of the brain in the preoptic and anterior hypothalamic region, a more numerous group of immunoreactive perikarya was located along the walls of the third ventricle in these same regions, and, finally, a few scattered cells were found in a more lateral position on both the internal and external sides of the tip of the fasciculus prosencephali lateralis. The periventricular cell population extended in the caudal direction until the posterior hypothalamus. Labelled fibers were always associated with these immunoreactive perikarya, and they were also found in the adjacent hypothalamic regions. A dense innervation of the median eminence was also detected. These data are compared with previous studies in mammals and birds that had identified more restricted populations of immunoreactive cells and the possible sources of the observed discrepancy are discussed. The functional significance of the present data is also briefly analyzed. PMID- 7884049 TI - Mu, delta, and kappa opioid receptor mRNA expression in the rat CNS: an in situ hybridization study. AB - The mu, delta, and kappa opioid receptors are the three main types of opioid receptors found in the central nervous system (CNS) and periphery. These receptors and the peptides with which they interact are important in a number of physiological functions, including analgesia, respiration, and hormonal regulation. This study examines the expression of mu, delta, and kappa receptor mRNAs in the rat brain and spinal cord using in situ hybridization techniques. Tissue sections were hybridized with 35S-labeled cRNA probes to the rat mu (744 1,064 b), delta (304-1,287 b), and kappa (1,351-2,124 b) receptors. Each mRNA demonstrates a distinct anatomical distribution that corresponds well to known receptor binding distributions. Cells expressing mu receptor mRNA are localized in such regions as the olfactory bulb, caudate-putamen, nucleus accumbens, lateral and medial septum, diagonal band of Broca, bed nucleus of the stria terminalis, most thalamic nuclei, hippocampus, amygdala, medial preoptic area, superior and inferior colliculi, central gray, dorsal and median raphe, raphe magnus, locus coeruleus, parabrachial nucleus, pontine and medullary reticular nuclei, nucleus ambiguus, nucleus of the solitary tract, nucleus gracilis and cuneatus, dorsal motor nucleus of vagus, spinal cord, and dorsal root ganglia. Cellular localization of delta receptor mRNA varied from mu or kappa, with expression in such regions as the olfactory bulb, allo- and neocortex, caudate putamen, nucleus accumbens, olfactory tubercle, ventromedial hypothalamus, hippocampus, amygdala, red nucleus, pontine nuclei, reticulotegmental nucleus, motor and spinal trigeminal, linear nucleus of the medulla, lateral reticular nucleus, spinal cord, and dorsal root ganglia. Cells expressing kappa receptor mRNA demonstrate a third pattern of expression, with cells localized in regions such as the claustrum, endopiriform nucleus, nucleus accumbens, olfactory tubercle, medial preoptic area, bed nucleus of the stria terminalis, amygdala, most hypothalamic nuclei, median eminence, infundibulum, substantia nigra, ventral tegmental area, raphe nuclei, paratrigeminal and spinal trigeminal, nucleus of the solitary tract, spinal cord, and dorsal root ganglia. These findings are discussed in relation to the physiological functions associated with the opioid receptors. PMID- 7884050 TI - Plasticin, a newly identified neurofilament protein, is preferentially expressed in young retinal ganglion cells of adult goldfish. AB - The adult goldfish retina and optic nerve display continuous growth, plasticity, and the capacity to regenerate throughout the animal's life. The intermediate filament proteins in this pathway are different from those in adult mammalian nerves, which do not continuously grow or normally regenerate. One novel intermediate filament protein of the goldfish visual pathway is plasticin, which is synthesized in ganglion cells and transported into the optic nerve. Using specific polyclonal antibodies raised against a plasticin fusion protein, we investigated the distribution of this protein in the normal retina and nerve and in the retina and nerve following optic nerve crush. In the normal pathway, plasticin was localized predominantly to the axons of very young ganglion cells; however, there was considerable immunoreactivity in older axons as they approach the chiasm. In addition, following optic nerve crush, all ganglion cell somata and their axons proximal to the crush site became equally immunoreactive. The results suggest that plasticin may contribute to axonal growth, plasticity, and regeneration. PMID- 7884051 TI - Differential physiology and morphology of motor axons to ventral longitudinal muscles in larval Drosophila. AB - Morphological and physiological characteristics of the two major motor axons supplying the commonly studied ventral longitudinal muscle fibers (6 and 7) of third-instar Drosophila melanogaster larvae were investigated. The innervating terminals of the two motor axons differ in the size of their synapse-bearing varicosities. The terminal with the larger varicosities also fluoresces more brightly when stained with the vital fluorescent dye 4-(4-diethylaminostyryl)-N methylpyridinium iodide (4-Di-2-Asp) and occupies a larger total contact area on the muscle fiber. Through selective simultaneous recording of synaptic currents from identified boutons in living preparations during elicitation of synaptic potentials, it was shown that the axon with the smaller varicosities generates a large excitatory junction potential (EJP) in muscle 6 and that the axon with the larger varicosities generates a smaller EJP. Short-term facilitation is more pronounced for the smaller EJP. In preparations treated with 4-Di-2-Asp, the fluorescence of smaller varicosities increases with stimulation that elicits the large EJPs, indicating an activity-dependent entry of calcium that enhances mitochondrial fluorescence. The differences in morphology and physiology of the two axons are similar to, though less pronounced than, those observed in "phasic" and "tonic" motor axons of crustaceans. PMID- 7884053 TI - Infertility in the mare. PMID- 7884052 TI - Effects of retinal lesions upon the distribution of nicotinic acetylcholine receptor subunits in the chick visual system. AB - Immunohistochemistry was used in this study to evaluate the effects of retinal lesions upon the distribution of neuronal nicotinic acetylcholine receptor subunits in the chick visual system. Following unilateral retinal lesions, the neuropil staining with an antibody against the beta 2 receptor subunit, a major component of alpha-bungarotoxin-insensitive nicotinic receptors, was dramatically reduced or completely eliminated in all of the contralateral retinorecipient structures. On the other hand, neuropil staining with antibodies against two alpha-bungarotoxin-sensitive receptor subunits, alpha 7 and alpha 8, was only slightly affected after retinal lesions. Decreased neuropil staining for alpha 7 like immunoreactivity was only observed in the nucleus of the basal optic root and layers 2-4 and 7 of the optic tectum. For alpha 8-like immunoreactivity, slight reduction of neuropil staining could be observed in the ventral geniculate complex, griseum tecti, nucleus lateralis anterior, nucleus lentiformis mesencephali, layers 4 and 7 of the tectum, and nucleus suprachiasmaticus. Taken together with previous data on the localization of nicotinic receptors in the retina, the present results indicate that the beta 2 subunit is transported from retinal ganglion cells to their central targets, whereas the alpha 7 and alpha 8 subunit immunoreactivity appears to have a central origin. The source of these immunoreactivities could be, at least in part, the stained perikarya that were observed to contain alpha 7 and alpha 8 subunits in all retinorecipient areas. In agreement with this hypothesis, the beta 2 subunit of the nicotinic acetylcholine receptors was not frequently found in perikarya of the same areas. PMID- 7884054 TI - Tuberculosis in the brushtail possum (Trichosurus vulpecula) after intratracheal inoculation with a low dose of Mycobacterium bovis. AB - Six possums were each inoculated with approximately 125 colony-forming units of Mycobacterium bovis via a cannula inserted per os into the trachea. Five other possums were sham inoculated and housed separately. At postmortem examination 55 to 57 days after inoculation, all six infected possums showed extensive macroscopical lesions of tuberculosis in the lungs and bronchial lymph nodes and some also had lesions in the liver, kidney, spleen and hepatic lymph nodes. Mycobacterium bovis was isolated from all of these possums. No evidence of M. bovis infection was detected in the five control animals. In the M. bovis infected possums, microscopical examination of organs and lymph nodes demonstrated a much wider distribution of lesions than did macroscopical examination. The location of early lesions indicated that the paracortical region of the lymph nodes, the marginal zone and periphery of lymphoid follicles in the spleen, and the cortex of the kidney were predilection sites for lesions resulting from haematogenous spread of infection. This method for reproducing bovine tuberculosis in the possum was more suitable for experimental studies than previously published methods. PMID- 7884055 TI - Resistance of castrated male horses to attempted establishment of the carrier state with equine arteritis virus. AB - Twelve geldings all became infected when inoculated intranasally with the KY-84 strain of equine arteritis virus (EAV), a strain previously shown to be capable of establishing the carrier state in the stallion. With the exception of one animal that showed no effects other than pyrexia, all of the geldings developed clinical signs characteristic of equine viral arteritis (EVA). The geldings were febrile for varying periods within the range of 2-10 days after inoculation. Viraemia occurred from day 2 onwards, for periods varying from 9 to at least 19 days. Nasal shedding of virus began 2-4 days after inoculation and persisted for periods ranging from 7-14 days. All geldings "seroconverted" to EAV by day 11, with serum neutralization titres ranging from 8 to 64. The titres ranged from 8 to 32 after 4 weeks. Low concentrations of EAV were detected in the kidney and blood of one gelding killed 30 days after inoculation and in the blood of another killed after 57 days. Virus was not isolated from any tissue or fluid sample collected from the remaining 10 geldings, all of which were killed between days 30 and 148. The findings confirm that persistent EAV infection is unlikely to occur in geldings and support the results of previous studies, which demonstrated that testosterone plays an essential role in the establishment and maintenance of the carrier state. PMID- 7884056 TI - Lipofuscin and abnormalities in colloid in the equine thyroid gland in relation to age. AB - Lipofuscin accumulation and other histological changes in thyroid tissue, previously reported to be age-related, were studied in 31 horses aged up to 35 years. The number of lipofuscin granules relative to thyrocytes increased from birth to 5 years of age. There was a wide individual variation in the number of lipofuscin granules in thyrocytes in mature horses, but this was not directly related to age. Several abnormalities were identified in thyroid colloid. The prevalence of spherites, lipofuscin granules, nucleated cells and shreds of colloid increased with age, but the prevalence of calcium oxalate crystals, erythrocytes, basophilic zones and solid fragments of colloid did not. In horses younger than 7 years, particularly large lipofuscin granules were found in thyrocytes of a small proportion of follicles which also contained abnormal colloid. Such follicles became more common in older horses without being accompanied by large lipofuscin granules. No correlation was found between granule numbers and frequency of colloid abnormalities. These results cast doubt on the traditional assumption that lipofuscin is indigestible cellular residue, since there was little evidence for excretion of granules. It is postulated that lipofuscin in this tissue may be a normal stage in lysosomal catabolism. PMID- 7884058 TI - Haematological and serum biochemical changes in the rat due to protein malnutrition and gossypol-ethanol interactions. AB - The effects of protein malnutrition on haematological and serum biochemical values were evaluated in gossypol-treated rats which were simultaneously fed with ethanol. Gossypol caused anaemia, leucopenia and thrombocytopenia in malnourished animals, suggesting a depression of bone marrow activity. Gossypol also caused a significant elevation of serum alkaline phosphatase and alanine aminotransferase activities and increases in the concentrations of Mg++ and Ca++ with reduced albumin, regardless of the nutritional status. These changes were more severe with malnutrition. Ethanol alone caused a thrombocytopenia but no other significant haematological changes. However, it appeared to cause derangement of lipid and protein metabolism as reflected in serum cholesterol and urea. The toxic effects seen in gossypol-treated rats were significantly reduced in animals simultaneously given ethanol. As the livers of gossypol-treated rats were significantly heavier than in these animals, it seems possible that ethanol consumption enhances the ability of the liver to metabolize gossypol, thereby reducing its accumulation and consequently its toxicity. However, further studies are needed to determine the mechanisms responsible. PMID- 7884059 TI - A congenital abnormality of calves, suggestive of a new type of arthropod-borne virus infection. AB - About 1000 calves with a congenital disease were born in Kagoshima prefecture, Japan, between October 1990 and October 1991, the peaks of the epidemic being in March and July 1991. Of 85 abnormal calves examined pathologically and serologically, 70 appeared to have been suffering from a viral disease. Of these 70 animals, 17 had lesions bearing some resemblance to those of the diseases produced by Akabane, Chuzan, Aino, bluetongue and bovine viral diarrhoea-mucosal disease viruses-diseases known to occur in Kagoshima-but serum samples contained no antibodies to these viruses or to infectious bovine rhinotracheitis virus. This suggested the occurrence of a new type of viral infection in southern Japan. Six of the 17 calves were born dead and the others manifested clinical signs such as weakness, difficulty in sucking, inability to stand, vertigo, opisthotonus, staggering and weak eyesight or blindness. They were of small size and showed domed head, scoliosis, arthrogryposis, maxillary retraction, sunken eye, cataracts, and irregularities and defects of the teeth. At necropsy, almost all cases showed hydranencephaly, and many had cerebral defects and cerebellar hypoplasia or agenesis. Both cerebral and cerebellar lesions were seen in six cases, two of which showed a hypoplastic defect of the brain stem. Histopathological examination of the affected organs revealed gliosis, loss of cerebral parenchyma resulting from dilation of the ventricles, perivascular cuffing with round cells such as lymphocytes and plasma cells, proliferation of blood vessels, thick-walled blood vessels in the brain stem, dilation of mesencephalic aqueducts, cerebellar cortical dysplasia, decreased nerve cells in the ventral horn of the spinal cord, and myodysplasia of skeletal muscle. PMID- 7884057 TI - Hepatic accumulation of alpha-1-antitrypsin in chronic liver disease in the dog. AB - Alpha-1-antitrypsin deficiency has long been known to cause liver cirrhosis in man, but whether it does so in the dog is uncertain. To investigate this point 57 dogs with clinically and histopathologically diagnosed chronic liver disease were examined. Isoelectric focusing of blood serum from these dogs and from 25 clinically healthy dogs revealed three different types of alpha-1 antitrypsin, designated F(fast), I(intermediate) and S(slow). They appeared in both homozygous and heterozygous forms, the F type being seen most frequently. The I type was more common in cocker spaniels than in other breeds. Immunostaining for alpha-1 antitrypsin revealed that 37 diseased dogs had alpha-1 antitrypsin in the cytoplasm of their hepatocytes. Of these, 21 dogs had globular alpha-1 antitrypsin inclusions in the endoplasmic reticulum, indicating aggregated protein. Accumulated alpha-1 antitrypsin was found most frequently in dogs having the I and S types of alpha-1 antitrypsin, either homozygously or heterozygously. With a few exceptions, F-homozygotic dogs had no hepatocellular alpha-1 antitrypsin accumulation. As alpha-1 antitrypsin aggregation is lethal to hepatocytes and as cell death attracts mononuclear blood cells whose cytokines induce continued alpha-1 antitrypsin synthesis with subsequent risk of further alpha-1 antitrypsin accumulation, liver disease may thus be maintained. Whether alpha-1 antitrypsin aggregates actually initiate liver disease in dogs, as in man, remains to be elucidated by further biochemical investigation of the three canine alpha-1 antitrypsin types found. PMID- 7884060 TI - Pulmonary neuroendocrine carcinoma in a four-month-old dog. AB - A 4-month-old male Siberian Husky dog had a history of coughing, high fever and anorexia. Thoracic radiographs revealed increased radiographic density in the cranial and middle lobes of the right lung, with pleural effusion. Cytological examination of the pleural fluid suggested carcinomatous pleuritis. Right-side thoracotomy and resection of the cranial and middle lobes were performed. Histopathological examination of the resected tissue revealed an anaplastic large cell carcinoma. The tumour cells were positive for neuron specific enolase and also contained neuroendocrine granules. A particularly unusual feature of this case of pulmonary neuroendocrine carcinoma was the young age of the affected animal. PMID- 7884061 TI - An immunohistochemical study of an equine B-cell lymphoma. AB - The tissues of an 8-year-old thoroughbred castrated male horse with equine lymphoma were examined immunohistochemically. Neoplastic masses were observed in the mediastinum, mesenteric lymph nodes, gastric mucosa and serosa, liver capsule, and spleen capsule with associated lymph nodes. Histopathologically, the neoplastic cells were seen to consist predominantly of a mixture of well differentiated small and large types. Immunohistochemically, the small lymphoid cells were MHC class IIlow+ and PanT- and the large lymphoid cells were MHC class IIhigh+ and PanT-. These findings revealed that the neoplastic cells were of B lymphocyte lineage. PMID- 7884062 TI - Malignant mesothelioma with metastases and mast cell leukaemia in a cat. AB - Abdominal malignant mesothelioma was found in a 17-year-old, spayed female Japanese domestic cat with mast cell leukaemia. The mesothelioma was mainly located at the periphery of the pancreas, spleen and stomach, and showed metastases to the lung, an anterior mediastinal lymph node and lymph ducts in the tracheal mucosa. Micro-circulatory defects caused by the mast cell leukaemia may have been partly responsible for the distant metastases. PMID- 7884063 TI - The effects of bromocriptine and prolactin on porphyrin biosynthesis in the harderian gland of the male hamster, Mesocritecus auratus. AB - Porphyrin biosynthesis was examined in the Harderian gland of the male golden hamster by fluorometric assays of gland porphyrin content and by measuring the activity of a rate-limiting enzyme for haem biosynthesis, 5-aminolaevulinic acid synthase. Both porphyrin content and enzyme activity are low in normal male glands but were greatly raised in males castrated for 6 weeks. However, porphyrin synthesis remained at basal levels in castrates given the dopamine agonist bromocriptine; this suppression could be reversed by simultaneous prolactin administration, and castrated males receiving prolactin alone exhibited very high enzyme activity and porphyrin content. Bromocriptine also prevents the morphological feminisation of the Harderian gland which would normally occur after castration; again, the simultaneous administration of prolactin permits feminisation to occur. The results support the hypothesis that, while androgens have an inhibitory effect on porphyrin synthesis within this model, other factors, including prolactin, are permissive. PMID- 7884064 TI - The optimal depot fat composition for hibernation by golden-mantled ground squirrels (Spermophilus lateralis). AB - Golden-mantled ground squirrels (Spermophilus lateralis) are herbivores that hibernate during winter. Although little is known about the nutritional/physiological constraints on hibernation, numerous studies have demonstrated that increasing the amount of linoleic acid (a polyunsaturated fatty acid) in the diet enhances hibernation. This is probably because high linoleic acid diets reduce the melting points of the depot fats produced for hibernation which makes them more metabolizable at low body temperatures. This suggests that a major limitation on hibernation may be obtaining enough linoleic acid in the diet for proper hibernation. In all previous studies, however, the amount of linoleic acid in the diets of free-ranging animals was either not considered, or the range of dietary linoleic acid contents in the experiments was less than that of natural diets. It is thus not known whether the amount of linoleic acid available to hibernators under natural conditions actually limits their torpor patterns. A series of laboratory feeding and hibernation experiments were conducted with S. lateralis and artificial diets with different linoleic acid contents that were either below or above the linoleic acid content of the natural diet. The results demonstrated that when dietary linoleic acid contents are either below or above natural levels, hibernation ability is greatly reduced. Hibernation ability was reduced when the squirrels were maintained on a high linoleic acid diet probably by the production of toxic lipid peroxides in brown adipose tissues. The results indicate that there is an optimal level of dietary linoleic acid for proper hibernation, and this is equal to that of the natural diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884065 TI - Changes in milk composition during lactation in three species of insectivorous bats. AB - Changes in milk composition are described for three species of free-ranging insectivorous bats (Myotis lucifugus, M. velifer, and Tadarida brasiliensis) from early to mid (peak) lactation. Dry matter and energy concentrations in milk increased from early to mid-lactation. In M. lucifugus and T. brasiliensis, but not M. velifer, these increases were due largely to a rise in fat concentration, since protein and carbohydrate remained relatively constant. Energy content of milk (kJ.g-1) for each species from early through mid-lactation was related to dry matter (DM) as follows: M. lucifugus (y = 0.31 DM-0.32, r2 = 0.68), M. velifer (y = 0.48 DM-5.08, r2 = 0.99), and T. brasiliensis (y = 0.37 DM-1.51, r2 = 0.61). Comparison of the effect of sampling method on milk composition of T. brasiliensis indicated that fat, dry matter, and energy concentrations increased significantly from pre-dawn to pre-noon samples. Relatively high fat and low water levels in T. brasiliensis milk may reflect the limited access that lactating females have to free water, as well as need to minimize mass of stored milk during long foraging trips. Conversely, lower fat concentrations and higher water levels in milk in M. lucifugus and M. velifer may relate to the propensity for colonies of these two species to roost and forage near bodies of water. In addition, differences in milk fat concentrations observed among the three species may correlate to daily suckling schedules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884066 TI - Digestive performance and selective digesta retention in the long-nosed bandicoot, Perameles nasuta, a small omnivorous marsupial. AB - Bandicoots are opportunistic omnivores that feed on invertebrates, fungi and both epigeal and hypogeal plant parts. We examined the performance of the digestive tract of the long-nosed bandicoot (Perameles nasuta) in terms of intake and total digestibility, patterns of excretion of inert digesta markers, and likely sites of digesta retention, on two diets designed to mimic part of their natural plant and insect diets. On the insect diet (mealworm larvae), bandicoots virtually maintained body mass at a digestible energy intake of 511 kJ.kg-0.75.day-1 and were in strongly positive nitrogen balance. In contrast, on the plant diet (shredded sweet potato), bandicoots ate only one-third as much digestible energy, lost 7% body mass, and were in negative nitrogen balance. Mean retention times of two particle markers on the plant diet (27.5 and 27.0 h) were more than double those on the insect diet (12.4 and 11.2 h), and on both diets the mean retention time of the fluid digesta marker was greater than those of the particle markers, indicating consistent selective retention of fluid digesta in the gut. It was seen radiographically than in mealworm-fed bandicoots major sites of digesta retention were the distal colon and rectum, whereas in the sweet potato-fed animals the caecum and proximal colon were principal sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884067 TI - ACTH, cortisol and glucose responses after administration of vasopressin in cattle and sheep. AB - The present study compared the effects of vasopressin on plasma concentrations of corticotropin, cortisol and glucose in cattle and sheep. After intravenous injection of 1, 0.1 and 0.01 microgram vasopressin per kg body weight, the plasma vasopressin concentration increased proportionally to the injected dose, and this increase was similar in cattle and sheep. Doses of 1 and 0.1 microgram per kg body weight of vasopressin triggered significant responses of corticotropin, cortisol and glucose in cattle and sheep. The corticotropin response to both doses was significantly greater in sheep, whereas the glucose response was greater in cattle. The cortisol response did not differ between species. The lowest dose of vasopressin (0.01 microgram per kg body weight) still induced a significant cortisol response without a substantial effect on plasma corticotropin, suggesting that a direct action of vasopressin on the adrenals may contribute to the observed cortisol response. The results demonstrate that vasopressin increases plasma levels of corticotropin, cortisol and glucose in cattle, as it does in sheep, but the intensities of the corticotropin and glucose responses to vasopressin differ between cattle and sheep. The reasons for these differences remain to be clarified. PMID- 7884068 TI - Current and future prospects for oral health science and technology. PMID- 7884069 TI - Research, technology transfer, and dentistry. AB - The periodontal discipline illustrates the need for dentists to be doctors specializing in oral medicine. Research findings are tending toward more complex and possibly lengthy treatment with drugs and/or growth factors, necessitating a curriculum with more emphasis on pharmacology, medical management, critical review of clinical trial results, and evaluation of risk-benefit ratios. PMID- 7884070 TI - Financing dental education. PMID- 7884071 TI - A quarter century of changes in oral health in the United States. AB - This paper provides an overview of the oral health status of Americans since the 1960s. Data from seven national surveys, conducted between 1960 and 1987, have been presented. Estimates of coronal and root caries, periodontal diseases, and tooth loss were reviewed. In addition, data on edentulism and oral cavity and pharyngeal cancer were included. Although the purpose of this paper is descriptive rather than analytical, some important trends have been noted: The number of children who were free from dental caries increased dramatically between 1963 and 1987. By 1987, almost one-half of school children between the ages of 5 and 17 were caries-free. Among those children with dental decay, the number of teeth affected has also declined. The oral health of adults also improved during the 27-year period included in this review. In particular, the mean number of missing teeth and the percentage of edentulous adults have declined substantially. Trends in periodontal diseases were difficult to determine due to changes in the measures of periodontal diseases utilized in the surveys. In the most recent survey of employed U.S. adults, approximately 44 percent were found to have gingivitis and slightly more than 13 percent had periodontal pockets 4-5 mm in depth. Approximately 30,000 new cases of oral cavity and pharyngeal cancer were diagnosed in 1993, resulting in approximately 8,000 deaths. African Americans have higher incidence and mortality rates than white Americans and also have a much lower five-year survival rate. PMID- 7884072 TI - Licensure and certification of dentists and accreditation of dental schools. PMID- 7884073 TI - A review of methods used to project the future supply of dental personnel and the future demand and need for dental services. PMID- 7884075 TI - Dental education at the crossroads--summary. PMID- 7884074 TI - Variation, treatment outcomes, and practice guidelines in dental practice. PMID- 7884076 TI - Issues in dental curriculum development and change. AB - Lessons from other places present several diverse suggestions for the dental curriculum's continuing improvement. Models from other professional education venues (medical schools), conceptual frameworks for self-reflection (ethos), and the scientific bases for learning and teaching (cognitive psychology) demonstrate that an interplay of factors must be addressed to advance the curriculum. PMID- 7884077 TI - Inheritance of resistance to Bacillus thuringiensis subsp. tenebrionis CryIIIA delta-endotoxin in Colorado potato beetle (Coleoptera: Chrysomelidae). AB - We investigated the genetic inheritance of Colorado potato beetle, Leptinotarsa decemlineata (Say), resistance to Bacillus thuringiensis CryIIIA delta-endotoxin. Standard reciprocal crosses and backcrosses between susceptible (S) and resistant (R) strains were used to determine the characteristics of resistance. Analysis of probit lines from the F1 reciprocal crosses indicated that B. thuringiensis delta endotoxin resistance was inherited autosomaly without maternal effects. We estimated the degree of dominance to be 0.77 and 0.76 for the (R x S) and (S x R) F1 generations, respectively, indicating that B. thuringiensis CryIIIA delta endotoxin resistance is conferred by incompletely dominant genes. Chi-square analysis of mortality responses of backcrossed offspring suggested that resistance might be caused by more than one locus. The stability of resistance was also studied by testing seventeen generations of resistant beetles after the selection pressure was removed. When the selection pressure was removed, the resistance level of the selected colony decreased after five generations. The resistance level did not decrease further when the selection was removed for > 12 generations. PMID- 7884078 TI - Effect of horn fly (Diptera: Muscidae) control during the spring on calf production by fall-calving beef cows. AB - In the spring of three consecutive years, horn fly, Haematobia irritans (L.), populations on fall-calving cows were reduced 82% for a 12-wk period using pyrethroid-impregnated ear tags. Horn fly populations on control cows exceeded 200 flies per animal for an average of 6 wk. Although the weights of cows and calves and body condition scores of both control and treated groups varied from year to year, a year x treatment effect (P < 0.01) on cow and calf weight gain was observed. However, differences in cow and calf production between treatments were not associated with differences in exposure to horn flies, and no significant effect on weaning weight of fall-born calves was associated with horn fly control. Calf body condition scores were also unaffected by horn fly control. PMID- 7884079 TI - Hawaiian tephritid fruit flies (Diptera): integrity of the infestation-free quarantine procedure for 'Sharwil' avocado. AB - In 1990, the infestation-free quarantine procedure for 'Sharwil' avocados grown in Kona, HI, was approved based on the assumption that fruits on trees are not hosts of tephritid fruit flies. In February 1992, the infestation-free quarantine procedure was suspended because of discovery of oriental fruit fly, Bactrocera dorsalis (Hendel), larval infestation in fruits on trees in certified orchards. Subsequently, an intensive field study was conducted to determine the level of tephritid fruit fly infestations in 'Sharwil' fruits. Results gathered negated two assumptions of the infestation-free quarantine procedure. First, the procedure assumed that only immature and mature green fruits are attached on trees; our data showed that, although most fruits on trees were either immature or mature green, a few ripe fruits occurred during the fruiting season. Second, the procedure assumed that mature green fruits have absolute resistance to tephritid fruit flies occurring in Hawaii; our field data showed that mature green 'Sharwil' avocados are suitable hosts of oriental fruit fly, albeit poor hosts. We present several hypotheses that may explain the failure of the infestation-free quarantine procedure for 'Sharwil' avocados. Morphological, physical, and chemical attributes of maturing 'Sharwil' fruits that may be useful in developing indices of fruit maturity and quality are also presented. PMID- 7884080 TI - Variation in tolerance to Bacillus thuringiensis among and within populations of the spruce budworm (Lepidoptera: Tortricidae) in Ontario. AB - Variation in tolerance to Bacillus thuringiensis Berliner subsp. kurstaki (strain HD-1-S-1980) among and within populations of the spruce budworm, Choristoneura fumiferana (Clemens), was assessed in the laboratory. Force-feeding assays using offspring of females collected as pupae from nine locations throughout Ontario and from a laboratory colony (DCF) demonstrated limited variation in tolerance among populations. Variation among populations was comparable with the variation observed among repeated assays with different batches of larvae from the DCF colony. Population LC50s were not significantly associated with age of the outbreak, host-plant species, incidence of the microsporidian Nosema fumiferanae (Thomson), or size of the female parent. Upper limits for genetic variation in tolerance were estimated by examining variation among full-sibling families within same populations. Mortality of individual families ranged from 6.5 to 70.9% within five field populations and from 2.7 to 93.3% within two laboratory colonies in response to a dose that caused a mean mortality of 40%. Familial factors accounted for 32.8% of the phenotypic variation in response across field populations, as compared with 3% for population factors. These data suggest that the phenotypic variation in tolerance to B. thuringiensis has a substantial genetic component and may provide a basis for evolution of resistance given sufficient selection pressure. PMID- 7884081 TI - Cardiac syndrome X: clinical characteristics and left ventricular function. Long term follow-up study. AB - OBJECTIVES: Our aim was to study the clinical characteristics and evolution of symptoms and left ventricular function in a clinically homogeneous group of patients with syndrome X (angina pectoris, positive exercise test results and normal coronary arteriograms). BACKGROUND: The syndrome of angina with normal coronary arteriograms is heterogeneous and encompasses different pathogenetic entities. These characteristics may contribute to the existing controversy concerning the cause of syndrome X. METHODS: We studied 99 patients with syndrome X (78 women, 21 men; mean age +/- SD 48.5 +/- 8 years). All underwent clinical characterization, ambulatory electrocardiographic (ECG) monitoring and echocardiographic assessment of left ventricular function during a follow-up period of 7 +/- 4 years. RESULTS: The syndrome was more common in women than in men. Of the women, 61.5% were postmenopausal before the onset of chest pain. All 99 patients had exertional angina, and 41 also had rest angina. The average duration of episodes of chest pain was > 10 min in 53% of patients. Sublingual nitrate was effective for relief of pain in 42% of patients. Transient ST segment depression was observed during ambulatory ECG monitoring in 64 patients and myocardial perfusion abnormalities in 22. During the first stage of the exercise test, 32 patients had an increase > 20 mm Hg in systolic blood pressure and showed an earlier onset of ST depression and shorter exercise time than did patients whose blood pressure increased < or = 20%. During follow-up, no deaths or myocardial infarctions occurred, ventricular function was unchanged (shortening fraction 35.4 +/- 4% vs. 35.6 +/- 3%; heart failure developed in only one patient), systemic hypertension occurred in eight patients and conduction disturbances in four. Symptoms lessened in 11 patients, were variable or unchanged in 64 and worsened in 24. CONCLUSIONS: Syndrome X, as defined in this study, occurs predominantly in postmenopausal women. Patients usually have chest pain typical for angina, but conventional antianginal treatment is not often successful. Myocardial perfusion abnormalities occur in a small proportion of patients. Long-term survival is not adversely affected, and deterioration of cardiac function rarely occurs. PMID- 7884082 TI - Strategies for prognostic assessment of uncomplicated first myocardial infarction: 5-year follow-up study. AB - OBJECTIVES: Our aim was to use noninvasive studies early after infarction to assess medium-term prognosis in patients with a first uncomplicated myocardial infarction. BACKGROUND: Although the use of early postinfarction assessment to gauge short-term prognosis in myocardial infarction is well established, there have been few comprehensive evaluations of noninvasive methods for assessing medium- and long-term prognosis. METHODS: We prospectively studied 115 consecutive patients < 65 years old with a first acute uncomplicated myocardial infarction to evaluate the prognostic role of predischarge cardiac studies. These included submaximal exercise testing, thallium-201 scintigraphy, radionuclide exercise ventriculography, two-dimensional echocardiography, ambulatory electrocardiographic (Holter) monitoring and cardiac catheterization. All patients without complications were followed up > or = 5 years. RESULTS: During the follow-up period, 78 patients (68%) developed complications, which were severe in 37 (32%). Exercise thallium-201 scintigraphy yielded the highest percentage (77%) for correctly classified patients. It also had the highest predictive value for complications (97%) and severe complications (92%) when it was used in association with exercise testing and radionuclide ventriculography. The addition of cardiac catheterization did not improve on the predictive power of noninvasive studies. Four decision trees (exercise testing + echocardiography, exercise testing + radionuclide ventriculography, thallium-201 + echocardiography, thallium-201 + radionuclide ventriculography) allowed stratification of all patients in a high, intermediate or low risk category. The combination of thallium-201 scintigraphy and radionuclide ventriculography yielded the best results (90% predictive value for complications if the outcome of both tests was positive), but there were no significant differences with the other models. CONCLUSIONS: Any combination of a test detecting residual ischemia or functional capacity, or both (exercise testing or thallium-201 scintigraphy), and a test assessing ventricular function (echocardiography or radionuclide ventriculography) results in useful prognostic information in patients with an uncomplicated first acute myocardial infarction. PMID- 7884083 TI - Transesophageal dobutamine stress echocardiography in the evaluation of coronary artery disease. AB - OBJECTIVES: The goal of this study was to determine the feasibility, safety, sensitivity and specificity of transesophageal dobutamine stress echocardiography for the detection of coronary artery disease. BACKGROUND: Dobutamine stress echocardiography has been shown to be an extremely sensitive and specific noninvasive technique for the detection of myocardial ischemia. However, inadequate transthoracic images preclude the use of dobutamine stress echocardiography in a small but significant group of patients. Transesophageal echocardiography provides better resolution than that obtained with routine transthoracic imaging. METHODS: Patients scheduled for routine cardiac catheterization underwent transesophageal dobutamine stress echocardiography. All patients underwent coronary arteriography within 48 h of the study, and lesion severity was determined by quantitative coronary angiography. Significant coronary obstruction was defined as stenosis > 50%. RESULTS: Fifty-one male patients were enrolled in the study; six were excluded for technical reasons. There were no adverse outcomes or complications. Of 27 patients with significant coronary artery disease, 22 had positive study results (sensitivity 82%). Of 13 patients without significant obstructive coronary disease, 1 had a false positive study result (specificity 93%). In patients with a minimal lumen diameter < 1.25 mm, sensitivity was > 80%, and in patients with a minimal lumen diameter > 1.5 mm, sensitivity was < 70%, suggesting that lesions with a minimal lumen diameter < 1.25 mm are more likely to be physiologically significant. CONCLUSIONS: Transesophageal dobutamine stress echocardiography is a feasible, safe and accurate technique for the detection of myocardial ischemia. There are inherent limitations to this technique in that transesophageal echocardiography must be performed. Transesophageal dobutamine stress echocardiography may allow extension of dobutamine stress testing to patients with inadequate transthoracic echocardiographic imaging and may provide an opportunity for further research applications. PMID- 7884084 TI - Comparison of thallium-201 single-photon emission computed tomography and electrocardiographic response during exercise in patients with normal rest electrocardiographic results. AB - OBJECTIVES: This study compared the diagnostic accuracy of exercise thallium-201 single-photon emission computed tomography (SPECT) with the exercise electrocardiographic (ECG) response in patients with normal baseline ECG results. BACKGROUND: Previous studies comparing exercise thallium imaging with exercise electrocardiography have included patients with abnormal rest ECG results that may have biased the results in favor of thallium imaging. METHODS: Of 321 patients with a pretest likelihood of coronary artery disease of 70 +/- 29% (mean +/- SD) who underwent exercise stress testing and coronary angiography, 68 had no coronary artery disease; 94 had one-vessel disease; 79 had two-vessel disease; and 80 had three-vessel or left main coronary artery disease. RESULTS: The diagnostic accuracy of SPECT was higher than that of the ECG response (79% vs. 49%, p < 0.0001). Patients with extensive (left main or three-vessel) coronary artery disease were older and had a lower work load, lower heart rate, greater ST segment depression and more extensive perfusion abnormalities than patients with no disease or one- or two-vessel disease. Multivariate discriminant analysis of exercise and thallium variables identified multivessel thallium abnormalities (F = 35), exercise heart rate (F = 18) and extent of ST segment depression (F = 6) as independent predictors of extensive disease. Of the 80 patients with left main or three-vessel disease, 37 (46%) had > or = 2-mm ST segment depression, 44 (55%) had multivessel SPECT abnormalities, and 61 (76%) had either > or = 2-mm ST depression or multivessel SPECT abnormalities (p = 0.0005 vs. the ECG response; p = 0.01 vs. SPECT). CONCLUSIONS: In patients with an intermediate to high pretest probability of coronary artery disease and normal baseline ECG results, SPECT is superior to the ECG response in detecting coronary disease. Further, SPECT provides incremental power in identifying patients with extensive (left main or three-vessel) coronary disease. PMID- 7884085 TI - Differential progression of complex and smooth stenoses within the same coronary tree in men with stable coronary artery disease. AB - OBJECTIVES: We sought to compare the evolution of complex and smooth stenoses within the same coronary tree in patients with stable coronary artery disease. BACKGROUND: Progression of coronary stenosis has prognostic significance and may be influenced by local and systemic factors. Stenosis morphology is a determinant of disease progression, but no previous study has systematically assessed progression of complex and smooth stenoses within the same patient. METHODS: We studied 50 men with stable angina who 1) had one complex coronary stenosis and one smooth stenosis in different noninfarct-related coronary vessels at initial coronary angiography, and 2) had a second angiogram after a median interval of 9 months (range 3 to 24). Patients with lesions > or = 10 mm long, at a major branching point or with > 85% diameter reduction were not included. Coronary lesions were measured quantitatively from comparable end-diastolic frames. Stenosis morphology was determined qualitatively by two independent observers. RESULTS: All patients remained in stable condition during follow-up. Progression, defined as an increase in diameter stenosis by > or = 15% was seen in only eight complex stenosis (16%) but in no smooth lesions (p < 0.01). The severity of complex stenoses changed more than that of corresponding smooth stenoses (mean +/ 1 SD 5.8 +/- 13% vs. -0.06 +/- 6%, p < 0.01). On average, the annual rate of growth was 11.4 +/- 28% and 1.5 +/- 14% for complex and smooth lesions, respectively (p < 0.01). CONCLUSIONS: Few coronary stenoses progress rapidly in stable angina. Complex and smooth coronary stenoses progress at different rates within the same coronary tree. complex stenosis morphology itself is an important determinant of progression of stenosis in patients with apparently clinically stable coronary artery disease. PMID- 7884086 TI - Improvement of global and regional left ventricular function by percutaneous transluminal coronary angioplasty after myocardial infarction. AB - OBJECTIVES: This study was designed to evaluate how elective percutaneous transluminal coronary angioplasty of the infarct-related vessel after acute myocardial infarction affects global ejection fraction and regional wall function. BACKGROUND: The severity of the residual stenosis of the infarct related artery after thrombolysis is an important predictor of changes in left ventricular function; however, the optimal time to restore complete perfusion in the infarct area has not been determined. METHODS: We prospectively evaluated patients with a first myocardial infarction, postinfarction ischemia and residual high grade stenosis with reduced flow in the infarct-related artery who underwent successful coronary angioplasty. The group comprised 74 patients (61 men, 13 women with a mean age +/- SD of 55.9 +/- 9.9 years). Global ejection fraction and infarct region function (expressed as area ejection fraction) were angiographically measured before coronary angioplasty (3.9 +/- 2.1 weeks after infarction) and on routine follow-up study 6 +/- 1 months after angioplasty. RESULTS: Restenosis with reduced flow occurred in 15 patients (20%). The global ejection fraction in patients with complete flow at follow-up increased significantly from 56.8% +/- 12% to 62.3% +/- 12.5% (p < 0.001). Regional wall motion of the infarct area increased from 12.1% to 22.5% (p = 0.001) in patients with anterior wall infarction and from 20.4% to 28.5% (p = 0.002) in those with inferior wall infarction. In patients with restenosis there was no difference at follow-up either in global ejection fraction (from 47.7% +/- 7.7% to 47.1% +/- 12.7%, p = 0.57) or in regional wall motion of the infarct area. CONCLUSIONS: Global and regional myocardial dysfunction due to postinfarction ischemia lessens significantly after successful coronary angioplasty of the infarct-related coronary artery with long-term sustained normal, complete flow. In contrast, restenosis with reduced flow prevents long-term improvement of left ventricular function. PMID- 7884087 TI - Detailed clinical and angiographic analysis of transluminal extraction coronary atherectomy for complex lesions in native coronary arteries. AB - OBJECTIVES: The purpose of this study was to describe the results of transluminal extraction coronary atherectomy in native coronary arteries. BACKGROUND: Transluminal extraction coronary atherectomy was approved by the Food and Drug Administration for use in native coronary arteries and vein grafts. METHODS: Between December 1988 and July 1992, transluminal extraction coronary atherectomy was performed in 181 native coronary arteries in 175 patients. A detailed angiographic and clinical assessment was performed. RESULTS: Quantitative angiography (mean +/- SD) revealed an increase in minimal lumen diameter from 1.0 +/- 0.6 mm before to 1.3 +/- 0.7 mm after atherectomy, to 2.1 +/- 0.8 mm after final treatment (p < 0.001), corresponding to a diameter stenosis of 70 +/- 16%, 61 +/- 21% and 36 +/- 21%, respectively (p < 0.001). Final procedural success (final diameter stenosis < 50%, no major complications) was achieved in 84%. Adjunctive angioplasty was used after atherectomy in 152 lesions (84%) to further enlarge lumen dimensions (130 lesions, 72%), salvage technical failures (2 lesions, 1%) and reverse atherectomy-induced abrupt closures (20 lesions, 11%). Clinical complications included death (2.3%), Q wave myocardial infarction (3.4%) and emergency bypass surgery (2.8%). The strongest independent correlate of major clinical complications was development of abrupt closure immediately after atherectomy (p = 0.01). Clinical follow-up of 92% of eligible patients revealed clinical restenosis (repeat intervention, late bypass surgery, myocardial infarction or death) in 28.5%. Angiographic follow-up of 83% of eligible lesions revealed a restenosis rate (diameter stenosis > 50%) of 61%. CONCLUSIONS: Transluminal extraction coronary atherectomy is limited by a modest degree of lumen enlargement, frequent need for adjunctive angioplasty and a high restenosis rate. For complex lesions in native coronary arteries, transluminal extraction coronary atherectomy appears to offer no advantage over conventional balloon angioplasty. PMID- 7884088 TI - Clinical and lesion morphologic determinants of coronary angioplasty success and complications: current experience. AB - OBJECTIVES: This study evaluated the validity of the American College of Cardiology/American Heart Association ABC lesion classification scheme and its modifications. BACKGROUND: With the continued refinement in angioplasty technique and equipment evolution, the lesion morphologic determinants of immediate angioplasty outcome have changed significantly. Hence, the validity of the classification scheme has been questioned. METHODS: We assessed the lesion morphologic determinants of immediate angioplasty outcome in 729 consecutive patients who underwent coronary angioplasty of 994 vessels and 1,248 lesions. RESULTS: Angioplasty success was achieved in 91% of lesions, and abrupt closure occurred in 3%. Success was achieved in 96%, 93% and 80% of type A, B and C lesions, respectively (A vs. B, p = NS; B vs. C, p < 0.001; A vs. C, p < 0.001; A vs. B1, p = NS; A vs. B2, p = 0.03; B1 vs. B2, p = 0.02; B2 vs. C, p < 0.001; C1 vs. C2, p = NS). Abrupt closure occurred in 2.1%, 2.6% and 5% of type A, B and C lesions, respectively (A vs. B, B vs. C, A vs. C and A vs. B1, all p = NS; B1 vs. B2, p = 0.01; B2 vs. C1, p = NS; C1 vs. C2, p = 0.04). Type B characteristics had a success rate ranging from 74% to 95% and an abrupt closure rate ranging from 2.2% to 14%. Type C characteristics had a success rate ranging from 57% to 88% and an abrupt closure rate ranging from 0% to 16%. Longer lesions, calcified lesions, diameter stenosis of 80% to 99% and presence of thrombus were predictive of a lower success rate. Longer lesions, angulated lesions, diameter stenosis of 80% to 99% and calcified lesions were predictive of an abrupt closure. CONCLUSIONS: The previously proposed classification schemes are outdated and need to be changed for application in current angioplasty practice. Analyzing specific lesion morphologic characteristics rather than applying a simple lesion classification score when evaluating angioplasty outcome may be more useful because it provides a more precise profile of the lesion and allows better patient stratification and selection. PMID- 7884089 TI - Stent implantation of saphenous vein graft aorto-ostial lesions in patients with unstable ischemic syndromes: immediate angiographic results and long-term clinical outcome. AB - OBJECTIVES: This study examined the immediate angiographic and long-term clinical results of stenting saphenous vein graft aorto-ostial stenosis at a single center. BACKGROUND: Data on the feasibility, safety and short- and long-term clinical results of stent implantation in aorto-ostial lesions in patients with unstable angina are limited. METHODS: Palmaz or Palmaz-Schatz stents were deployed in 29 patients (mean [+/- SD] age 70 +/- 10 years) with complex (B2 or C) vein graft aorto-ostial lesion morphology. All patients had angina at rest; 23 (79%) had a previous myocardial infarction; and 13 (45%) had two previous bypass operations (mean graft age 9 +/- 5 years). Mean left ventricular ejection fraction was 42 +/- 13%. RESULTS: Thirty-two stents were deployed in 25 new and 4 restenotic aorto-ostial lesions. Ten additional stents were implanted in five patients for eight lesions other than at ostial locations. Stent implantation was successful in all patients. There was no death, Q wave myocardial infarction, bypass surgery or stent thrombosis in the first 30 days. Stenting improved minimal lumen diameter from 0.7 +/- 0.5 mm (95% confidence interval [CI] 0.5 to 0.8) to 3.3 +/- 0.5 mm (CI 3.2 to 3.5) and percent diameter stenosis from 80 +/- 13% (CI 75% to 85%) to 1 +/- 12% (CI -3% to 6%) (p < 0.001 for both variables). Immediate loss from recoil was 0.2 +/- 0.2 mm (CI 0.2 to 0.3), corresponding to a percent recoil of 7 +/- 5% (CI 5% to 9%). Clinical follow-up in all patients at a mean of 11 +/- 8 months revealed that 27 patients (94%) were free of death or myocardial infarction. Bypass surgery and balloon angioplasty were required in one (3%) and two (6%) patients, respectively. In 21 (88%) of the remaining 24 patients, symptoms were lessened by two or more symptom classes. CONCLUSIONS: Palmaz or Palmaz-Schatz stent implantation for saphenous vein graft aorto-ostial stenosis has a high likelihood of immediate success and is associated with a large immediate gain in lumen diameter. Thirty-day and long-term adverse event rates are low. These data suggest that stenting saphenous vein graft aorto-ostial lesions is an acceptable therapeutic option in selected elderly patients with unstable angina and large-diameter vessels. PMID- 7884090 TI - Adverse prognostic significance of concentric remodeling of the left ventricle in hypertensive patients with normal left ventricular mass. AB - OBJECTIVES: We examined the prognostic significance of concentric remodeling of the left ventricle in patients with essential hypertension and normal left ventricular mass on echocardiography. BACKGROUND: An echocardiographic pattern of concentric remodeling of the left ventricle has been associated with clinical features of increased cardiovascular risk, but the independent prognostic value of this finding in hypertensive patients with normal left ventricular mass has not been established. METHODS: Six hundred ninety-four patients with essential hypertension and normal left ventricular mass (< 125 g/m2) on echocardiography were prospectively followed up for < or = 7.7 years (mean 2.71). Baseline echocardiography and 24-h noninvasive ambulatory blood pressure monitoring were performed in all patients at the time of initial diagnostic evaluation. Concentric remodeling was defined by the thickness of the septum or posterior wall divided by the left ventricular radius at end-diastole > or = 0.45. RESULTS: Prevalence of concentric remodeling was 39.2%. During follow-up there were 29 cardiovascular morbid events. Cardiovascular morbidity, expressed as the combined number of fatal and nonfatal events per 100 patient-years, was 1.53 in the overall study group, 1.12 in the subgroup with normal left ventricular geometry and 2.39 in that with concentric remodeling. After assessment of the independent association with several covariates (age, gender, diabetes, left ventricular mass index, mean clinic blood pressure and mean 24-h ambulatory blood pressure) in Cox proportional hazard models, the risk of cardiovascular morbid events was higher in the group with concentric remodeling than in that with normal geometry (relative risk 2.56, 95% confidence interval 1.20 to 5.45, p < 0.01). CONCLUSIONS: Concentric remodeling of the left ventricle, defined by the thickness of the septum or posterior wall divided by the left ventricular radius at end-diastole > or = 0.45, is an important and independent predictor of increased cardiovascular risk in hypertensive patients with normal left ventricular mass on echocardiography. PMID- 7884091 TI - Prognosis of left ventricular geometric patterns in the Framingham Heart Study. AB - OBJECTIVES: The goal of this study was to determine the incremental prognostic value of left ventricular geometric patterns beyond that provided by cardiovascular disease risk factors, including left ventricular mass. BACKGROUND: Left ventricular geometry may be classified into the following four mutually exclusive groups on the basis of left ventricular mass and relative wall thickness: concentric hypertrophy (increased mass and increased relative wall thickness), eccentric hypertrophy (increased mass and normal relative wall thickness), concentric remodeling (normal mass and increased relative wall thickness) and normal geometry (normal mass and normal relative wall thickness). The prognosis associated with these patterns in a population-based sample is not known. METHODS: Proportional hazards regression models were used to evaluate the prognostic importance of left ventricular geometry in 3,216 subjects in the Framingham Heart Study who were > or = 40 years old and free of clinically apparent cardiovascular disease, after adjustment for traditional cardiovascular risk factors and left ventricular mass. The follow-up period was 8 years. RESULTS: Subjects with concentric hypertrophy had the worst prognosis, followed by those with eccentric hypertrophy, concentric remodeling and normal geometry. Subjects with concentric hypertrophy also had the highest left ventricular mass. The association between type of geometry and prognosis was largely attenuated by adjustment for baseline differences in left ventricular mass. The odds ratio for incident cardiovascular disease in subjects with concentric hypertrophy compared with those who had normal geometry was 1.3 (95% confidence interval [CI] 0.8 to 2.1) in men and 1.2 (95% CI 0.6 to 2.3) in women after adjustment for other cardiovascular risk factors, including left ventricular mass. CONCLUSIONS: In a population-based sample of subjects without cardiovascular disease, knowledge of left ventricular geometry provided little prognostic information beyond that available from left ventricular mass and traditional cardiovascular risk factors. PMID- 7884092 TI - Left ventricular geometry, pathophysiology and prognosis. PMID- 7884093 TI - Empiric determination of the transition from concentric hypertrophy to congestive heart failure in essential hypertension. AB - OBJECTIVES: Our aim was to determine whether there is a final transition from left ventricular hypertrophy to congestive heart failure in the late stage of essential hypertension. BACKGROUND: A theoretic model using the concept of systolic transmural nonuniform wall thickening was applied to develop a concentric two-shell geometry allowing evaluation of the mechanics of circumferential midwall fibers. METHODS: We evaluated pressure-volume data from 46 normal control subjects (control group) and 70 patients with hypertension: 33 without hypertrophy (hypertension only group), 14 with hypertrophy (hypertrophy group) and 23 with heart failure in addition to hypertrophy (heart failure group). RESULTS: End-diastolic volume index was higher in the heart failure group than in the control group (p < 0.01). Although left ventricular wall thickness and mass index were increased in both the hypertrophy and the heart failure group, concentricity indexes as assessed by ratios of left ventricular wall thickness to dimension and mass index to end-diastolic volume index were maximal in the former. Although endocardial and standard midwall fractional shortening did not differ among the control, hypertension only and heart failure groups, that of the modified midwall by concentric two-shell geometry was decreased in the hypertrophy and the heart failure groups (p < 0.05). The Hotelling T2 test and Mahalanobis distance clearly discriminated the latter two groups with end systolic stress and modified midwall fractional shortening relation. CONCLUSIONS: A fitting segmented regression model predicted a progression to hypertrophy and identified a transition from hypertrophy to heart failure by a combination of modified midwall fractional shortening and concentricity indexes. PMID- 7884094 TI - Lack of association of recreational cocaine and alcohol use with left ventricular mass in young adults. The Coronary Artery Risk Development in Young Adults (CARDIA) study. AB - OBJECTIVES: This study examined the associations of left ventricular mass with self-reported cocaine and alcohol use prevalent in the young adult population. BACKGROUND: Increased left ventricular mass has been associated with long-term use of cocaine and alcohol; however, few of the published studies have been population based. METHODS: Data from 3,446 black and white participants (mean age 29.9 years) in the Coronary Artery Risk Development in Young Adults (CARDIA) study were used to examine the associations between echocardiographically measured left ventricular mass obtained from 1990 to 1991 and self-reported cocaine and alcohol use. Categories of cocaine use were those who denied ever using cocaine (n = 2,122), experimental users who admitted to cocaine use only 1 to 10 times in their lifetime (n = 755) and recurrent users who admitted to cocaine use > 10 times in their lifetime (n = 568). For alcohol consumption, categories were abstainers who consistently denied any alcohol consumption in the year before each of the three CARDIA examinations (n = 275), occasional users who admitted consuming alcohol less than once a week or not at all during the year before the third examination (n = 1,322), moderate users who consumed 1 to 209 ml of alcohol/week during the year before the third examination (n = 1,524) and heavy users who consumed > or = 210 ml of alcohol/week during the year before the third examination (n = 323). Estimated power to detect a 10% difference in left ventricular mass between groups was > 80%. RESULTS: For white women, left ventricular mass was significantly higher among those who reported 1 to 10 lifetime uses of cocaine than in never-users (128.5 g [SE 2.0] vs. 122.7 g [SE 1.4], p = 0.002). There were no other significant differences in left ventricular mass among categories of cocaine or alcohol use in unadjusted analyses or among analyses controlling for age, body mass index, alcohol or cocaine use, physical activity, cigarette smoking status and systolic blood pressure. CONCLUSIONS: At the levels of consumption reported, neither cocaine nor alcohol use was associated with left ventricular mass in this cohort of healthy young adults. PMID- 7884095 TI - Circadian pattern of ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators. AB - OBJECTIVES: This study examined the temporal patterns of ventricular tachycardia detections by implantable cardioverter-defibrillators for circadian variability. BACKGROUND: Previous studies of circadian arrhythmia patterns have been methodologically limited by very brief observational periods. Late-generation implantable cardioverter-defibrillators accurately record the times of arrhythmia detections during unlimited follow-up. METHODS: Forty-three patients with late generation implantable cardioverter-defibrillators were followed up for 226 +/- 179 days (mean +/- SD). The times of all recorded episodes of ventricular tachyarrhythmias were retrieved from the data log of each device during follow up. RESULTS: The weighted distribution of 830 ventricular tachyarrhythmia episodes from the 43 patients fit a single harmonic sine curve model with a peak between 2 and 3 P.M. (95% confidence interval 1:13 to 4:13 P.M., R = 0.75, p < 0.05). The distributions of spontaneously terminating episodes, episodes receiving device therapy, episodes receiving shocks and episodes in the absence of antiarrhythmic therapy also fit the sine curve model (all R = 0.53 and 0.73, all p < 0.05), all with peak frequencies between 2:08 and 3:09 P.M. and 95% confidence intervals for peak frequencies between 11:38 A.M. and 5:07 P.M. Episodes recorded during continuous antiarrhythmic drug therapy did not fit the model (p > 0.05). CONCLUSIONS: The distribution of ventricular tachyarrhythmias detected by late-generation implantable cardioverter-defibrillators follows a circadian pattern, with a peak tachycardia frequency between noon and 5 P.M. This pattern was not observed in patients receiving antiarrhythmic drug therapy. Knowledge of circadian periodicity for these events has implications for patient management. PMID- 7884096 TI - Definition of the best prediction criteria of the time domain signal-averaged electrocardiogram for serious arrhythmic events in the postinfarction period. The Cardiac Arrhythmia Suppression Trial/Signal-Averaged Electrocardiogram (CAST/SAECG) Substudy Investigators. AB - OBJECTIVES: The goal of this study was to establish guidelines for the prognostic use of the time domain signal-averaged electrocardiogram (ECG) after myocardial infarction. BACKGROUND: Previous studies of the prognostic use of the signal averaged ECG in postinfarction patients had one or more of the following limitations: a small study group, empiric definition of an abnormal recording and possible bias in the selection of high risk groups or classification of arrhythmic events, or both. To correct for these limitations, a substudy was conducted in conjunction with the Cardiac Arrhythmia Suppression Trial (CAST). METHODS: Ten centers recruited 1,211 patients with acute myocardial infarction without application of the ejection fraction or Holter criteria restrictions of the main CAST protocol. Several clinical variables, ventricular arrhythmias on the Holter recording, ejection fraction and six signal-averaged ECG variables were analyzed. Patients with bundle branch block were excluded from the analysis, and the remaining 1,158 were followed for up to 1 year after infarction. The classification of arrhythmic events was reviewed independently by the CAST Events Committee. RESULTS: During an average (+/- SD) follow-up of 10.3 +/- 3.2 months, 45 patients had a serious arrhythmic event (nonfatal ventricular tachycardia or sudden cardiac arrhythmic death). A Cox regression analysis with only the six signal-averaged ECG variables indicated that the filtered QRS duration at 40 Hz > or = 120 ms (QRSD-40 Hz) at a cutpoint > or = 120 ms was the most predictive criterion of arrhythmic events. In a regression analysis that included all clinical, Holter and ejection fraction variables, a QRSD-40 Hz > or = 120 ms was the most significant predictor (p < 0.0001). The positive, negative and total predictive accuracy and odds ratio for QRSD-40 Hz > or = 120 ms were 17%, 98%, 88% and 8.4, respectively, and improved to 32%, 97%, 94% and 16.7, respectively, after combination with ejection fraction < or = 40% and complex ventricular arrhythmias on the Holter recording. CONCLUSIONS: The signal-averaged ECG predicts serious arrhythmic events in the first year after infarction better than do clinical, ejection fraction and ventricular arrhythmia variables, and QRSD-40 Hz > or = 120 ms provides the best predictive criterion in this clinical setting. PMID- 7884097 TI - Effects of oral pirenzepine on heart rate variability and baroreceptor reflex sensitivity after acute myocardial infarction. AB - OBJECTIVES: Our aims were 1) to assess whether oral pirenzepine could increase indexes of cardiac vagal activity in postinfarction patients, and 2) to compare the effects of this agent with those of transdermal scopolamine. BACKGROUND: Depression of vagal tone and reflexes predicts a poor arrhythmic outcome after myocardial infarction. Interventions for shifting the sympathovagal balance toward vagal dominance are now of increased clinical interest. Intravenous pirenzepine increases RR interval variability in normal volunteers, a finding that could have therapeutic implications if confirmed in postinfarction patients after oral administration of the drug. METHODS: In a single-blind placebo controlled crossover trial, short-term RR interval variability and baroreceptor reflex sensitivity were evaluated in 20 patients an average of 19 +/- 6 days after infarction. Analysis was performed during control conditions and during administration of placebo, oral pirenzepine and transdermal scopolamine. RESULTS: Compared with placebo, at a dose of 25 mg twice daily, pirenzepine significantly increased all time and frequency domain measures of RR interval variability and augmented baroreceptor reflex sensitivity by 60% (mean +/- 1 SD 10.4 +/- 5.9 vs. 6.5 +/- 3.2 ms/mm Hg, p = 0.0007). Pirenzepine and scopolamine showed a similar vagomimetic effect, but the overall incidence of adverse effects was lower with pirenzepine (1 [5%] of 20 vs. 10 [50%] of 20). CONCLUSIONS: In patients with a recent myocardial infarction, oral pirenzepine proved equal to transdermal scopolamine in significantly increasing indexes of cardiac vagal activity. These data suggest that oral pirenzepine may have a therapeutic potential for preventing malignant ventricular arrhythmias after infarction. PMID- 7884098 TI - Left ventricular mass increases during cardiac allograft vascular rejection. AB - OBJECTIVES: This study evaluated whether left ventricular mass increases during cellular or vascular (humoral) cardiac allograft rejection. BACKGROUND: An increase in left ventricular mass during cellular cardiac allograft rejection has been described by other investigators, although controversy has existed over the validity of these findings. Left ventricular mass changes have not been evaluated in the setting of vascular (humoral) cardiac allograft rejection. METHODS: To determine the effect of allograft rejection on left ventricular mass, we retrospectively reviewed endomyocardial biopsy results and corresponding echocardiograms in 41 cardiac transplant recipients undergoing treatment for allograft rejection. Left ventricular mass was assessed by two-dimensional echocardiography using the method of Schiller. Maintenance immunosuppression included cyclosporine in all patients. RESULTS: Although significant changes in left ventricular wall thickness, mass and dimensions were not observed in patients experiencing moderate or severe cellular allograft rejection (International Society for Heart and Lung Transplantation grades III and IV, n = 27), marked changes were noted in patients with vascular (humoral) rejection (n = 14). Patients with vascular rejection demonstrated an echocardiographic mean (+/- SEM) increase in left ventricular wall mass (from 109 +/- 17 to 151 +/- 17 g), and left ventricular wall thickness (from 1.3 +/- 0.1 to 1.6 +/- 0.1 cm) during the rejection episode. Additionally, vascular rejection was associated with a trend toward an increase in left ventricular systolic dimension (from 2.6 +/- 0.1 to 3.0 +/- 0.2 cm) and a decrease in left ventricular fractional shortening and increased incidence of hemodynamic compromise with rejection (50% for vascular vs. 11% for cellular rejection). CONCLUSIONS: Left ventricular mass increases during episodes of vascular (humoral) rejection, but there is no significant change in left ventricular mass during cellular cardiac allograft rejection. PMID- 7884099 TI - Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: evidence for late reinnervation. AB - OBJECTIVES: This study attempted to determine whether cardiac sympathetic reinnervation occurs late after orthotopic heart transplantation. BACKGROUND: Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic nerves. Iodine-123 (I-123) MIBG cardiac uptake reflects intact myocardial sympathetic innervation of the heart. Cardiac transplant recipients do not demonstrate I-123 MIBG cardiac uptake when studied < 6 months from transplantation. However, physiologic and biochemical studies suggest that sympathetic reinnervation of the heart can occur > 1 year after transplantation. METHODS: We performed serial cardiac I-123 MIBG imaging in 23 cardiac transplant recipients early (< or = 1 year) and late (> 1 year) after operation. In 16 subjects transmyocardial norepinephrine release was measured late after transplantation. RESULTS: No subject had visible I-123 MIBG uptake on imaging < 1 year after transplantation. However, 11 (48%) of 23 subjects developed visible cardiac I-123 MIBG uptake 1 to 2 years after transplantation. Only 3 (25%) of 12 subjects with a pretransplantation diagnosis of idiopathic cardiomyopathy demonstrated I-123 MIBG uptake compared with 8 (73%) of 11 with a pretransplantation diagnosis of ischemic or rheumatic heart disease (p = 0.04). All 10 subjects with a net myocardial release of norepinephrine had cardiac I-123 MIBG uptake; all 6 subjects without a net release of norepinephrine had no cardiac I-123 MIBG uptake. CONCLUSIONS: Sympathetic reinnervation of the transplanted human heart can occur > 1 year after operation, as assessed by I-123 MIBG imaging and the transmyocardial release of norepinephrine. Reinnervation is less likely to occur in patients with a pretransplantation diagnosis of idiopathic cardiomyopathy than in those with other etiologies of congestive heart failure. PMID- 7884100 TI - Atrial emptying with orthotopic heart transplantation using bicaval and pulmonary venous anastomoses: a magnetic resonance imaging study. AB - OBJECTIVES: We hypothesized that orthotopic heart transplantation with bicaval and pulmonary venous anastomoses preserves atrial contractility. BACKGROUND: The standard biatrial anastomotic technique of orthotopic heart transplantation causes impaired function and enlargement of the atria. Cine magnetic resonance imaging (MRI) allows assessment of atrial size and function. METHODS: We studied 16 patients who had undergone bicaval (n = 8) or biatrial (n = 8) orthotopic heart transplantation without evidence of rejection and a control group of 6 healthy volunteers. For all three groups, cine MRI was performed by combining coronal and axial gated spin echo and gradient echo cine sequences. Intracardiac volumes were calculated with the Simpson rule. Atrial emptying fraction was defined as the difference between atrial diastolic and systolic volumes, divided by atrial diastolic volume, expressed in percent. All patients had right heart catheterization. RESULTS: Right atrial emptying fraction was significantly higher in the bicaval (mean [+/- SD] 37 +/- 9%) than in the biatrial group (22 +/- 11%, p < 0.05) and similar to that in the control group (48 +/- 4%). Left atrial emptying fraction was significantly higher in the bicaval (30 +/- 5%) than in the biatrial group (15 +/- 4%, p < 0.05) and significantly lower in both transplant groups than in the control group (47 +/- 5%, p < 0.05). The left atrium was larger in the biatrial than in the control group (p < 0.05). Cardiac index, stroke index, heart rate and blood pressure were similar in the transplant groups. CONCLUSIONS: Left and right atrial emptying fractions are significantly depressed with the biatrial technique and markedly improved with the bicaval technique of orthotopic heart transplantation. The beneficial effects of the latter technique on atrial function could improve allograft exercise performance. PMID- 7884101 TI - Correspondence of left ventricular ejection fraction determinations from two dimensional echocardiography, radionuclide angiography and contrast cineangiography. AB - OBJECTIVES: This study assessed the agreement of left ventricular ejection fraction determinations from two-dimensional echocardiography, radionuclide angiography and contrast cineangiography. BACKGROUND: Previously published reports suggest that two-dimensional echocardiography, radionuclide angiography and contrast cineangiography are equally acceptable methods of assessing left ventricular ejection fraction on the basis of high coefficients of correlation. However, correlation of methods does not necessarily imply agreement. METHODS: In a prospective analysis, 25 consecutive subjects all had two-dimensional echocardiography and radionuclide angiography performed within 10 days of each other in the cardiology department of metropolitan community hospital. A retrospective computer search (Medline) revealed seven studies, using the coefficient of correlation (r), comparing two-dimensional echocardiographic left ventricular ejection fraction (n = 268) with radionuclide angiographic (n = 174) or contrast cineangiographic (n = 119) left ventricular ejection fractions. RESULTS: The eight individual studies (n = 293) comparing two-dimensional echocardiography with either radionuclide angiography or contrast cineangiography exhibited coefficients of correlation ranging from 0.78 to 0.93. Agreement analysis using the method of Bland and Altman was performed by averaging the results obtained from the two techniques and determining how disparate any single ejection fraction was (with 95% confidence limits) from the mean value. Agreement ranged from 23% to 42% around the mean ejection fraction. The average lack of agreement between the two methods for all studies involved was 17%, with an average r value of 0.86. CONCLUSIONS: Left ventricular ejection fraction determinations by means of two-dimensional echocardiography, radionuclide angiography and contrast cineangiography exhibit high correlation and only moderate agreement. High correlation does not always imply high agreement. These results suggest that, when validated by agreement analysis, multiple studies may not be necessary in appropriate clinical situations, potentially reducing costs. PMID- 7884102 TI - Video-assisted thoracoscopic vascular ring division in infants and children. AB - OBJECTIVES: This study evaluated our early experience with video-assisted thoracoscopic vascular ring division and compared this approach with division by means of a conventional open thoracotomy. BACKGROUND: Video-assisted thoracoscopic techniques reduce surgical trauma and have been applied to several adult thoracic procedures; however, pediatric applications have been limited. We developed instruments and techniques for video-assisted thoracoscopic vascular ring division in the pediatric population. METHODS: We compared patient characteristics, operative results and postoperative hospital courses of all patients undergoing vascular ring division by a video-assisted approach with a historical control group of all patients undergoing division by an open thoracotomy between January 1991 and December 1992. RESULTS: Eight patients (median age 5 months, range 40 days to 5.5 years; median weight 6.2 kg, range 1.8 to 17.1) underwent video-assisted thoracoscopic vascular ring division. Four had a double aortic arch with an atretic left arch and a left ligamentum, and four had a right aortic arch with aberrant left subclavian artery and a left ligamentum. All eight had successful ring division with symptomatic relief and no mortality. A limited thoracotomy was performed in three patients to divide patent vascular structures, and the hospital period was prolonged in one because of chylothorax. These eight patients were compared with a historical cohort of eight pediatric patients having vascular ring division performed by a conventional thoracotomy. The two groups did not differ in age, weight, intensive care unit or postoperative hospital stay, duration of intubation or thoracostomy tube or hospital charges. Total operating room time was longer for the group undergoing video-assisted operation. CONCLUSIONS: Early results for video-assisted thoracoscopic vascular ring division are comparable to those of the conventional surgical approach. With further refinement in technique and instrumentation, video-assisted surgical intervention may become a viable alternative to open thoracotomy for management of the symptomatic vascular ring. PMID- 7884103 TI - Unroofed coronary sinus and coronary sinus orifice atresia. Implications for management of complex congenital heart disease. AB - OBJECTIVES: The aim of this study was to assess the morphology of the coronary sinus, its drainage and associated cardiac malformations when there is either complete unroofing of the coronary sinus or atresia of its connection to the right atrium. BACKGROUND: As more children with complex cardiac anomalies are accepted for primary surgical repair or palliation with cavopulmonary anastomoses, a knowledge of coronary sinus and systemic venous anomalies is important if coronary venous return is to be preserved and residual shunts avoided. METHODS: Twenty-six heart-lung specimens without a coronary sinus draining to the right atrium were identified from the Leiden collection of congenital heart malformations. These were classified into specimens with an unroofed coronary sinus and those with atresia of the coronary sinus orifice. Attention was paid to the associated cardiac malformations. RESULTS: In 14 (54%; confidence limits [CL] 35%, 73%) of 26 specimens, there was an unroofed coronary sinus, associated with persistence of the left superior caval vein. An inferoposterior location of an atrial septal defect was detected in 2 (14%; CL 4%, 33%) of 14. Atrial appendage anomalies were seen in 13 (93%; CL 79%, 106%) of 14 specimens, exemplified by both right and left isomerism. These were frequently associated with an atrioventricular septal defect (12 [86%; CL 67%, 104%] of 14). An atretic coronary sinus orifice was seen in 12 (46%; CL 27%, 65%) of 26. Atrial appendage anomalies (2 [17%; CL -4%, 38%] of 12) were rare in these cases. The drainage was then by way of a left superior caval vein or, in its absence, a coronary sinus to left atrial window. Ventricular hypoplasia was seen in both categories of coronary sinus abnormalities. Important ventricular hypoplasia was seen in 12 cases (46%; CL 27%, 65%). CONCLUSIONS: These findings emphasize the need to study coronary sinus drainage before procedures such as ligation or transcatheter coil embolization of a left superior caval vein, venous redirection or closure of a dorsal atrial septal defect are contemplated. These procedures might inadvertently lead to impairment of coronary venous return or persistence of an intracardiac shunt. PMID- 7884104 TI - Effects of physiologic and pharmacologic adrenergic stimulation on heart rate variability. PMID- 7884105 TI - Resilience to exercise detraining in healthy older adults. AB - OBJECTIVE: To determine the effects of stopping and restarting two types of exercise programs in older adults. DESIGN: A controlled, longitudinal study that utilized random assignment of volunteers. Treatments were exercise programs designed to improve cardiovascular or neuromuscular fitness. MEASUREMENTS: Dependent variables measured before and after implementation of treatments were: maximum oxygen consumption, oxygen pulse, treadmill and cycle training workloads, quadriceps isokinetic peak torque, quadriceps isokinetic total work, and quadriceps training workload. MAIN RESULTS: Exercise training was highly effective in improving cardiovascular endurance or muscular strength. Ten weeks of exercise detraining resulted in small losses in newly gained cardiovascular capacity but more noticeable losses in muscular strength. Exercise retraining was accomplished easily using cardiovascular or resistive exercises. The functional benefits of restarting a cardiovascular exercise program appeared additive despite a 10-week intervening period of exercise detraining. In this age group, cardiovascular exercise produced limited improvements in muscular strength, and resistive exercise training positively influenced cardiovascular exercise performance. CONCLUSIONS: Older adults are fairly resilient to 10 weeks of cardiovascular detraining and retain newly gained muscular strength for at least 5 weeks, despite an interruption of formal exercise. An occasional missed exercise session or temporary cessation of habitual exercise should not be a cause for distress in exercising older adults. Instead, they should realize the case with which they may restart their exercise program and also appreciate the generalized fitness benefits that can be ascribed to becoming more active. PMID- 7884106 TI - Older age and the underreporting of depressive symptoms. AB - OBJECTIVE: To determine whether older age is associated with a decrease in self reported depressive symptoms, independent of examiner-rated symptoms, in inpatients with major depression. DESIGN: Survey study. SETTING: Inpatient psychiatric units at a university medical center. PATIENTS: Eligible subjects were those over 20 years of age with a primary diagnosis of DSM-III-R major depression. Participation was sought from all subjects over 60 years of age and from every second or every third younger subject, depending on rater availability. Of 137 eligible subjects, 97 completed all study measures. MEASUREMENTS: The Beck Depression Inventory (BDI), as a measure of self-reported depressive symptoms, was the dependent variable. The Hamilton Rating Scale for Depression (Ham-D) was used to assess examiner-rated symptoms. MAIN RESULTS: Older age (P = .03) was associated negatively and examiner-rated depressive symptoms (P = .0001) were associated positively with BDI score. Other variables, including gender, education, age of depression onset, and medical illness burden, were not independently associated with BDI. Examination of depressive symptom subtotals (psychologic/affective vs. somatic/neurovegetative) revealed that only the self-reported psychologic/affective subtotal was significantly associated with age (P = .0018). CONCLUSIONS: Some older patients with clinically significant depression underreport their symptoms. When asking older patients about depressive symptoms, clinicians should view negative responses only within larger clinical contexts and should obtain information from other sources as needed. Similar concerns must temper interpretation of research that relies on subject self-report to study depression in late life. PMID- 7884107 TI - Medical care utilization among older HMO members with and without hypertension. AB - OBJECTIVES: To compare hospital utilization, health status, and sociodemographic characteristics of older persons with and without hypertension and to examine the nature of the association of hypertension with medical care utilization. DESIGN: A retrospective, nonexperimental study. SETTING: A large health maintenance organization (HMO), located in the Portland, Oregon and Vancouver, Washington areas, that provides comprehensive, prepaid benefits to its members. PARTICIPANTS: Approximately 4200 older (> or = 65 years) members enrolled in the Social HMO Demonstration Project. MEASUREMENTS: The dependent variables were (1) whether a member was hospitalized (0 = no; 1 = yes) and (2) the number of hospitalizations during the 12-month period before the return of the Health Status Form, a mail questionnaire. The predictor variables were high blood pressure and other medical conditions, health status, and sociodemographic characteristics. Patients classified as hypertensive were those who self-reported high blood pressure and who received two or more dispensings for antihypertensive medications. RESULTS: Older hypertensives were more likely than older nonhypertensives to have been hospitalized (odds ratio (OR) = 1.14 (95% CI 1.01, 1.27)), self-report their health as only good or fair (P < .001), self-report IADL functional limitations (P < .001), and to be younger than nonhypertensives (P < .001). Utilization differences were similar after controlling for patients' age and gender. Factors independently associated with an increased likelihood of hospitalization were male gender (OR = 1.14 (1.00,1.31)), age (OR = 1.35 (1.00,1.81)), poor (OR = 1.32 (1.02,1.72)) or fair (OR = 1.20 (1.01,1.44)) self rated health status, functional limitations in activities of daily living (OR = 1.74 (1.48,2.03), and self-reported heart trouble (OR = 1.50 (1.34,1.68)), stroke (OR = 1.37 (1.15,1.64)), or cancer (OR = 2.89 (1.72,4.84)). Factors independently associated with a decreased likelihood of hospitalization were excellent self reported health (OR = 0.65 (0.47,0.90)), no physical impairments (OR = 0.59 (0.48,0.72)), and no circulation problems (OR = 0.85 (0.74,0.98)). CONCLUSIONS: Older hypertensive patients had poorer self-reported health, more functional limitations, used more hospital services, and were not as old as nonhypertensive older patients. To the extent that general health is improved by treatment of hypertension, appropriate treatment of high blood pressure may not only improve health, it may also reduce medical care utilization. Our findings offer further support for hypertension prevention, detection, and treatment programs designed to reduce or minimize hypertension's later medical complications and to reduce future utilization. PMID- 7884108 TI - Predicting bacteremia in older patients. AB - OBJECTIVE: To evaluate potential clinical predictors of bacteremia in hospitalized geriatric patients and to propose an individual risk score as an alternative to "subjective" clinical judgment for a more efficient approach in early recognition and treatment of bacteremia. DESIGN: A 16-month prospective study. SETTING: The University Geriatric Hospital of Geneva, Switzerland. PATIENTS: Four hundred thirty-eight patients aged 62 years or older in whom 558 episodes of bacteremia were suspected. MEASUREMENTS: The unit of evaluation was the blood culture episode, which was defined as a 48-hour period beginning with the drawing of the first blood for culture. An extensive precoded protocol, including clinical and biological data, was completed by the resident who requested the blood cultures. For each episode, the resident also provided a subjective assessment of the probability of bacteremia. Odds ratios and their variances were used to estimate the relative risks of potential predictors of bacteremia. The performance of a predictive clinical model based on risk score threshold was evaluated by means of a receiver-operating characteristic analysis. RESULTS: Of the 558 potentially bacteremic episodes investigated, 46 (8.2%) yielded positive blood cultures. The bacteremia rate was strongly associated with the type of episode: it reached 15.6% among the community-acquired (CA) episodes (those occurring within 48 hours of hospital admission) and 6.0% only among the hospital-acquired (HA) episodes (those occurring after the first two days of hospitalization). Predictors of bacteremia with highest relative risks included: bladder catheter removal, fever (> or = 38.5 degrees C), rigors, shock, total band count > or = 1500/mm3, and lymphocyte count < or = 1000/mm3. When assessed by episode type, it appeared that bladder catheter removal and rigors were good predictors of bacteremia in HA episodes only, whereas fever (> or = 38.5 degrees C) had a good predictive value in CA episodes only. The performance of the clinical model was two times better than the physician's subjective ability to predict bacteremia when the threshold of the risk score was fixed at two or more predictors per episode. CONCLUSIONS: These findings provide means to identify older hospitalized patients at high risk of bacteremia. Although the proposed predictive model will need further validation and more precise evaluation of the potential benefits, it may nevertheless be of some help in early recognition and treatment of bacteremia. PMID- 7884109 TI - Elevated plasma levels of interleukin-6 in postmenopausal women do not correlate with bone density. AB - OBJECTIVE: To determine if plasma levels of Interleukin-6 (IL-6) across the lifespan correlate with bone density or plasma osteocalcin. DESIGN: Cross sectional study. PARTICIPANTS: Forty-five healthy community-dwelling volunteers aged 25-74 years. Exclusion criteria were smoking use of medications known to affect bone metabolism (corticosteroids, heparin, thyroxine, thiazides, and anticonvulsants), and presence of chronic inflammatory disease. MEASUREMENTS: Bone density was measured by dual-energy X-ray absorptiometry at the femoral neck and lumbar spine. Plasma levels of IL-6 and osteocalcin were determined by ELISA and RIA, respectively. RESULTS: Plasma levels of IL-6 increased with advancing age (P < .0001) and correlated with postmenopausal status (P < .0001). No correlation was observed between plasma IL-6 level and bone mineral density at either the lumbar spine or femoral neck, and none was observed with plasma osteocalcin. CONCLUSIONS: The elevation of plasma IL-6 observed following menopause is consistent with the proposed importance of estrogen in the regulation of IL-6. These findings do not provide support for a role of IL-6 in determination of peak bone density or subsequent development of osteoporosis. However, it is possible that plasma levels of IL-6 differ from those in the bone microenvironment. PMID- 7884110 TI - Predictors of hospital mortality in older patients with subdural hematoma. AB - OBJECTIVE: To identify presenting characteristics of older patients with subdural hematoma who are unlikely to survive hospitalization. DESIGN: A retrospective cohort. PATIENTS: All patients > or = 65 years of age hospitalized at a tertiary care center from 1985-1990 with the primary diagnosis of subdural hematoma. MEASUREMENTS: Chart review was performed to characterize presenting clinical characteristics, hospital course, and outcome at the time of hospital discharge. MAIN RESULTS: Of the 157 eligible patients, 42% (66/157) were > or = 80 years of age. Although 30% of patients had no recorded trauma, 54% experienced a fall before hospitalization. Twenty-six percent (47/157) of patients had been on antithrombotic therapy (14 on coumadin, two on heparin, 31 on antiplatelet agents, one on both coumadin and an antiplatelet agent). Sixty percent of patients had no focal neurologic findings, and the mean Glasgow Coma Score was 12.3 (+/- 3.6). The hematoma was considered chronic in 49% (77/157) of cases, based on time from antecedent trauma or on neuroimaging criteria. Midline shift by neuroimaging was present in 69%. Overall hospital mortality was 31% (48/157). Using logistic regression to control for other factors, level of consciousness (Glasgow Coma Score < = 7) (OR = 10.4), age > or = 80 (OR = 3.7), duration of hematoma considered acute (OR = 2.7), and craniotomy (OR = 2.6) were significantly associated with hospital mortality. Presence of focal symptoms, previous antithrombotic medication use, nature of trauma, comorbidity score, and presence of midline shift were not associated with hospital mortality. CONCLUSIONS: Among older patients with subdural hematoma, level of consciousness, extreme old age, duration of the hematoma, and nature of the intervention were significantly associated with hospital mortality. These factors should help physicians in clinical decision making and formulation of advance directives for geriatric patients with subdural hematoma. PMID- 7884111 TI - Effectiveness of oral antibiotic treatment in nursing home-acquired pneumonia. AB - OBJECTIVE: To determine factors associated with success or failure of oral antibiotic treatment for nursing home-acquired pneumonia (NHAP). DESIGN: Retrospective study of outcomes for all identifiable NHAP cases in 1991. SETTING: The Nursing Home Services Program of St. Paul Ramsey Medical Center and 31 metropolitan St. Paul, Minnesota, community nursing homes. PARTICIPANTS: Nursing home (NH) cohort: 124 patients (mean age 85.2 years) with a new respiratory symptom and new infiltrate on portable chest X-ray for whom oral antibiotics were prescribed. Hospital cohort: 74 NH patients (mean age 84.3 years) admitted to hospital with new X-ray infiltrate and pneumonia diagnosis. Supportive care status patients were excluded. Forty-three physician/nurse practitioner (MD/NP) teams were represented. MEASUREMENTS: Nursing home cohort: Outcomes of hospitalization within 14 days or 30-day mortality. A discriminant model was applied to predict outcome and discriminant rule performance was analyzed. Hospital cohort: 30-day mortality. RESULTS: Of 198 episodes of NH pneumonia, 63% were treated in the facility; 30.6% (38) failed NH treatment. Thirty-day mortality was 13%. There was no examination by the MD or NP for 59% of NH-treated episodes. The hospital cohort had a higher mean pulse (P < .05) but a similar frequency of feeding dependence. Hospital cohort mortality was 17.6%. The NH treatment failure group had significantly higher proportions of pulse > 90/min, temperature > 100.5 degrees F, respirations > 30/min, feeding dependence, and mechanically altered diets. A discriminant model using these factors was significant (P = .002). The NH treatment failure rate was 11% for no factors present, 23% for two or fewer factors, and 59.5% for three or more (likelihood ratio 3.1). Thirty-two percent of the hospital cohort had zero or one factor present and were alive at 30 days. CONCLUSION: The majority of NHAP episodes were treated successfully with oral antibiotics, but 31% failed treatment in the NH. Patients with a mechanically altered diet or requiring feeding assistance by staff had significantly higher failure rates. Feeding dependence and need for a mechanically altered diet as well as abnormal vital signs are associated with oral antibiotic treatment failure. These factors should be considered in treatment decisions for NHAP. PMID- 7884112 TI - Life satisfaction and associated factors in older Hong Kong Chinese. AB - OBJECTIVE: To determine life satisfaction and its association with physical, functional, socioeconomic, psychological, and social support characteristics in Hong Kong Chinese aged 70 years and older. DESIGN: Cross-sectional study. SETTING: Territory-wide random sample of persons aged 70 years and older. SUBJECTS: A total of 843 men and 714 women were selected by random sampling, stratified by age and sex, from the Old age and Disability Allowance Register, after exclusion of subjects with cognitive impairment. MEASUREMENTS: Life satisfaction was assessed by the subjects' response to the question "Are you satisfied with life", using a 0 to 10-point linear scale. They were also asked to name the most important factor contributing to life satisfaction. Information was also obtained regarding physical health, functional ability, depressive symptoms, and socioeconomic factors. RESULTS: There was a weak association between score and age. Health, adequate income to meet living expenses, and caring relatives were rated the most important factors (> 65%). Some of these factors were also those associated with a high life satisfaction score. Factors associated with a life satisfaction score greater than 6 points were higher social class and educational attainment, adequate income to meet living expenses, satisfactory living arrangement, Christianity, good social support, participation in social activities, functional independence, good self-perceived health, good hearing and vision, daily exercise, absence of recurrent falls, and low depressive symptom score. Multiple logistic regression identified having two or more relatives and tertiary education as positive associated factors, whereas inadequate income to meet expenses, dissatisfaction with living arrangement, nonparticipation in religious group activities, and a high depressive symptom score were negative associated factors. CONCLUSION: In older Chinese, social factors such as the support provided by family members, as well as adequate income to meet living expenses, play a role equal to that of physical factors in contributing to life satisfaction. PMID- 7884113 TI - Clinical spectrum of tuberculosis in older patients. AB - OBJECTIVE: To investigate the clinical differences between old and young patients infected with Mycobacterium tuberculosis in a developing country. DESIGN: Retrospective chart and chest radiograph review. SETTING: A university-affiliated teaching hospital. PATIENTS: The medical records of patients with documented tuberculosis (TB) from January 1990 through December 1991 were analyzed. Clinical assessment included sex, age, diagnosis at first visit, past history, symptoms and signs, laboratory data, X-ray findings, bacteriological examinations, outcome, time elapsed from first visit to initiation of anti-TB therapy and the major determinants for starting anti-TB therapy. Statistical significances were analyzed by Student's t test and chi 2 tests. RESULTS: Among 205 patients with culture-proven TB, 57 were 65 years of age and older (range, 65 to 91; mean, 73) and 148 under 65 years of age (range, 16 to 64; mean, 41). There was a higher incidence of previous TB (26.3% vs. 16.2%) and diabetes mellitus (24.5% vs. 14.3%) in the elderly patients. Initial diagnosis of TB at first visit was less frequent in the elderly than in the young group (38.6% vs. 47.3%), although symptoms and signs at first visit were similar in each of the age groups. Radiographic presentation with mass lesions was more frequently encountered in elderly patients (10.5% vs. 2.1%, P < .05). Elapsed time from the first visit to suspicion of TB and the initiation of anti-TB therapy was frequently delayed in elderly patients (22 +/- 23 vs. 13 +/- 20 days, P < .05). The incidence of drug resistance (39% vs. 16%, P < .05) and unfavorable response to anti-TB therapy (17.5% vs. 3.4%, P < .05) were significantly higher in the older patients. CONCLUSIONS: Although clinical presentation of TB in the elderly did not differ significantly from that in younger patients, this study showed that diagnosis and treatment were more often delayed in the elderly, and there was a higher incidence of treatment failure. PMID- 7884114 TI - Effect of psyllium on absorption of co-ingested calcium. AB - OBJECTIVE: To determine whether psyllium fiber (in the form of Metamucil) interferes with absorption of calcium ingested at the same meal. DESIGN: Three way, randomized, cross-over study in 15 healthy postmenopausal women, with calcium-fortified orange juice as the calcium source in all three meals. The test load of calcium was 219 mg (approximately 5.5 mmol). One test meal contained Metamucil, providing 3.4 g psyllium fiber; one had an equivalent amount of neutral cellulose; the third had no added fiber. METHODS: The calcium-fortified orange juice was extrinsically labeled with 45Ca; calcium absorption fraction was calculated from the specific radioactivity of serum calcium at 5 hours after tracer ingestion. RESULTS: Fractional absorption of calcium from orange juice without added fiber averaged 0.341 +/- 0.059; in the presence of psyllium fiber, 0.317 +/- 0.067; and in the presence of neutral fiber, 0.354 +/- 0.083. While the absorption with cellulose was slightly higher than in the absence of fiber, and the absorption with psyllium was slightly lower, neither difference was statistically significant. However, the difference between added psyllium and cellulose was statistically significant (P < .05). CONCLUSION: Psyllium in the form of Metamucil makes little practical difference to availability of co ingested calcium when ingested at typical therapeutic doses. PMID- 7884115 TI - Evidence for inflammation as a cause of hypocholesterolemia in older people. PMID- 7884116 TI - Predictors of Pap smear screening in socioeconomically disadvantaged elderly women. AB - OBJECTIVE: The objective for this study was to identify predictors for participation in Pap smear screening in a socioeconomically disadvantaged older population. DESIGN AND SAMPLE: A cross-sectional survey design was used to examine data from 238 southern women 50 years of age and older who were recruited from 24 randomly selected congregate meal sites of the Council on Aging. MEASUREMENTS: The 45-item questionnaire covered demographics, Pap smear screening history, and colorectal cancer screening history. RESULTS: Among this older, very low income population, women who had never had Pap smears (17.2%) were significantly more likely to have no phone or to be unable to use a phone (adjusted odds ratio (aOR) = 4.1; 95% confidence interval (CI) 1.6-10.6), to have annual incomes of less than $5,800 (aOR = 3.1; 95% CI 1.1-9.0), to be widowed (aOR = 2.8; 95% CI 1.1-7.3), to have no family history of cancer (aOR = 3.3, 95% CI 1.3-10.0), to report having never had a rectal examination (aOR = 5.4, 95% CI 1.8-16.0), and not to have participated in a free fecal occult blood testing program (aOR = 5.0, 95% CI 2.0-10.0). CONCLUSIONS: These data, unique in including very low income (< $10,000) and older women (65 and over), found that income and access to a phone were strongly correlated with cervical cancer screening participation. Women who lacked external incentives for screening (being widowed and not having a family history of cancer) were less likely to obtain screening. This study's finding that "not having a phone" was a strong predictor for nonparticipation in cervical cancer screening has implications for national telephone-derived estimates of cervical cancer screening. PMID- 7884117 TI - A randomized comparison of intravenous amrinone versus dobutamine in older patients with decompensated congestive heart failure. AB - OBJECTIVE: To compare the hemodynamic effects of amrinone and dobutamine in patients 75 years of age or older who have severe congestive heart failure requiring invasive hemodynamic monitoring and inotropic support. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: Coronary care unit of a university teaching hospital. PARTICIPANTS: Fourteen patients > or = 75 years of age (mean 80.3 +/- 5.7 years) with refractory New York Heart Association class IV congestive heart failure. All patients had a cardiac index < 2.5 L/min/M2 (mean 1.8 +/- 0.3 L/min/M2), pulmonary capillary wedge pressure > or = 18 mm Hg (mean 26 +/- 10 mm Hg), and left ventricular ejection fraction < 40% (mean 26 +/- 10%). INTERVENTION: Patients were randomly assigned to treatment with 2-hour infusions of amrinone (n = 7) or dobutamine (n = 7) at fixed dosages of 5 and 10 micrograms/kg/min. MEASUREMENTS: Complete hemodynamic data were obtained at baseline and after each 2-hour medication infusion. Transthoracic two dimensional echocardiography was performed at baseline and after the 10 micrograms/kg/min medication dose. The primary analysis compared the effects of the two drugs on cardiac index and stroke volume index at each of the two dosages. RESULTS: Both amrinone and dobutamine had salutary hemodynamic effects, as indicated by improvements in cardiac index, stroke volume index, pulmonary capillary wedge pressure, and systemic vascular resistance (all P < .05 except effect of amrinone on stroke index and wedge pressure). Although the overall hemodynamic effects of amrinone and dobutamine were similar, stroke volume index was higher with dobutamine at the 10 micrograms/kg/min dose (35 +/- 7 ml/M2 vs 26 +/- 6 mL/M2; P = .045). Two dobutamine patients were withdrawn from the study after the 5 micrograms/kg/min dose due to adverse effects (tachycardia, increased ventricular ectopy). One additional patient in each group was noted to have ventricular arrhythmias not requiring termination of the protocol. CONCLUSIONS: Both amrinone and dobutamine are efficacious in improving hemodynamics in older patients with severe congestive heart failure caused by left ventricular contractile dysfunction. Despite the effect of aging on beta-adrenergic responsiveness, dobutamine is at least as effective as amrinone but may be associated with a higher incidence of arrhythmic side effects. PMID- 7884119 TI - Urine specimen collection from incontinent female nursing home residents. AB - OBJECTIVE: To determine if a clean catch technique can accurately diagnose bacteriuria among incontinent female nursing home residents. DESIGN: Cultures and dipstick screening test results from paired urine specimens, one collected by a clean catch technique and the other collected by sterile in-and-out catheterization, were compared. PARTICIPANTS: A total of 101 incontinent female nursing home residents who were being assessed for participation in a larger clinical intervention trial for incontinence. MEASUREMENTS: Each urine was tested by a dipstick method for leukocyte esterase and nitrite and sent to a bioclinical laboratory for quantitative culture. RESULTS: Positive and negative culture results matched in 92 of the 101 paired specimens. Using the catheter specimen as a gold standard, the clean catch had a sensitivity of 90%, specificity of 92%, positive predictive value of 81%, and a negative predictive value of 95%. In a population with symptoms suggestive of infection, among whom the prevalence of bacteriuria would likely be higher than in the asymptomatic residents we studied (e.g., 60% vs 30%), the positive predictive value would increase to 95%, but the negative predictive value would decrease to 86%. The concordance of the results of the urine screening tests was not as good, except for the detection of a positive leukocyte esterase test and a negative nitrite test. CONCLUSION: Incontinent female nursing home residents do not necessarily have to be catheterized in order to obtain an accurate quantitative urine culture. Our results using a careful clean catch technique are comparable to those previously reported using urine obtained from a urine-soiled diaper as well as those using a condom catheter technique in men. PMID- 7884118 TI - Dependence in activities of daily living as a risk factor for fall injury events among older people living in the community. PMID- 7884120 TI - Breast lump in an 85-year-old woman with dementia: a decision analysis. PMID- 7884121 TI - Urinary incontinence associated with dementia. AB - Urinary incontinence is common in patients with dementia and is more prevalent in demented than in nondemented older individuals. It occurs with equal or greater frequency in males than in females, and this contrasts with the female preponderance in community-based, general older populations. Since the etiology of incontinence in dementia is multifactorial, a comprehensive assessment of factors within and outside the lower urinary tract is essential. A careful clinical evaluation is sufficient to guide treatment in most cases. Further research is needed to determine the role of simple cystometry and more complex urodynamic investigation in these patients. Research on the management of urinary incontinence in demented patients has focused almost exclusively on toileting programs and drug treatments for detrusor hyperactivity. To date, anticholinergic and antispasmodic medications have not been shown to be effective in treating incontinence in demented persons. However, the few studies undertaken have been in the most severely mentally and physically deteriorated patients, and it is possible that these medications have greater efficacy in less impaired individuals. Prompted voiding regimens have been shown to reduce incontinence by an average of 32% and appear to be a useful approach in managing incontinence in some of these patients. However, unless staff management systems are employed, staff compliance with these programs diminishes with time and the labor costs involved may limit their applicability in nursing homes. Patients who are the most severely cognitively impaired, least mobile, and have the greatest frequency of incontinence derive the least benefit from toileting programs, and palliative measures may be more appropriate in these cases. PMID- 7884122 TI - Usefulness of M-mode, 2-dimensional, and Doppler echocardiography in the diagnosis, prognosis, and management of valvular aortic stenosis, aortic regurgitation, and mitral annular calcium in older patients. AB - OBJECTIVE: To review the diagnosis, prognosis, and management of valvular aortic stenosis, aortic regurgitation, and mitral annular calcium (MAC) with emphasis on older persons. DATA SOURCES: A computer-assisted search of the English-language literature (MEDLINE database) followed by a manual search of the bibliographies of pertinent articles. STUDY SELECTION: Studies on the diagnosis, prognosis, and management of valvular aortic stenosis, aortic regurgitation, and MAC were screened for review. Studies in older persons and recent studies were emphasized. DATA EXTRACTION: Pertinent data were extracted from the reviewed articles. Emphasis was on studies involving older persons. Relevant articles were reviewed in depth. DATA SYNTHESIS: Available data about the diagnosis, prognosis, and management of valvular aortic stenosis, aortic regurgitation, and MAC with emphasis on studies involving older persons were summarized. CONCLUSIONS: Valvular aortic stenosis, aortic regurgitation, and MAC are degenerative cardiac disorders which are common in older people. The presence and severity of these cardiac disorders are diagnosed by M-mode, 2-dimensional, and Doppler echocardiography. M-mode, 2-dimensional, and Doppler echocardiographic techniques are also very useful in the prognosis and management of these cardiac disorders in older persons. PMID- 7884123 TI - Health outcomes of post-hospital in-home team care: secondary analysis of a Swedish trial. AB - OBJECTIVE: To determine patient and treatment-related factors predictive of health outcomes. DESIGN: Secondary analysis of a randomized trial with 6-month follow-up. After using bivariate and three-way analysis in the total sample to screen outcome predictors and interactions among baseline variables, multivariate logistic regression was used to model outcomes. SETTING: A county general hospital in central Stockholm, and patients' homes nearby. PATIENTS: Hospital inpatients stable for discharge from acute care, having at least one chronic condition, and dependent in 1 to 5 Katz activities of daily life (ADLs) were included. Subjects (mean age = 81.1 years) were randomized to "team" (n = 150) or "usual care" (n = 99). INTERVENTIONS: Team patients were eligible for in-home primary care by an interdisciplinary team that included a physician, physical therapist, and 24-hour nursing services and geriatric consultation where necessary. "Usual-care" patients received standard district nurse-administered services at home upon hospital discharge. MEASUREMENTS: Demographic, functional status, and medical characteristics were measured at randomization. Outcomes included survival and higher ADL, instrumental ADL (IADL), and outdoor ambulation scores. MAIN RESULTS: Multiple medical, social, behavioral, and functional factors were associated with outcomes. Primary cardiac disease, number of prescription drugs, alcohol abstinence, and baseline mental status all impacted 6 month survival. Controlling for other factors, team care improved the likelihood of ambulation independent of personal assistance at follow-up (P = .027), treating an estimated 10 patients per 1 benefiting. Further, rehabilitative in home team care neutralized mortality and functional risk factors (low number of baseline contacts and coresidence) apparent in usual care. CONCLUSIONS: Heterogeneous clinical populations of older patients contain many prevalent characteristics important to outcomes. Secondary analysis of trials including interactions identifies treatable and untreatable risks, what program components may be effective, and who benefits. PMID- 7884124 TI - Exercise: the right prescription. PMID- 7884125 TI - Urinary incontinence and dementia: the perils of guilt by association. PMID- 7884126 TI - Increased mortality in older persons with hypocholesterolemia: cause or effect. PMID- 7884127 TI - Erythropoietin therapy for anemia. PMID- 7884128 TI - Futility in clinical practice. PMID- 7884129 TI - Is it heaven? Pleasant visual hallucinations in nonagenarians. PMID- 7884130 TI - Increased CSF pyruvate levels as a marker of impaired energy metabolism in Alzheimer's disease. PMID- 7884131 TI - Torsades de pointes in a nonagenarian. PMID- 7884132 TI - Pain assessment in the Alzheimer's patient. PMID- 7884133 TI - Our optometric heritage, the beginning of ophthalmic comanagement. PMID- 7884134 TI - The optometrist and the practice of low vision care. PMID- 7884135 TI - Optometric contributions to the vision rehabilitation network. PMID- 7884136 TI - High myopia trilogy. PMID- 7884137 TI - Vision rehabilitation therapy for the bioptic driver. AB - BACKGROUND: The use of a bioptic telescope for driving purposes has been controversial. This controversy has been fueled by confusion over which vision skills are needed for driving and how they are measured and developed. To make this issue even more complex, there are no standardized programs for evaluating patients and teaching basic vision skills needed to drive safely. METHODS: This paper will address vision skills and abilities which, intuitively, play an important role in driving. We will also propose a training program for the successful development of these skills since they relate to active driving, specifically, with a bioptic telescope. RESULTS: Our experience in working with patients who are partially sighted in the driving program seems to indicate that these patients have confidence in using their bioptic telescopic lens system for driving purposes. They appreciate and recognize the responsibility that comes with the independence that is gained from driving with the bioptic system. CONCLUSIONS: It is our hope that by providing these patients with appropriate care and training, we afford them the opportunity to adjust to their bioptic driving lens system and enjoy more years of independence and safe driving. PMID- 7884138 TI - New ergonomic stand magnifiers. AB - BACKGROUND: Stand magnifiers are not satisfactory for reading and other near visual requirements for many low vision patients. METHODS: Four new stand magnifiers have been developed with ergonomic advantages such as a comfortable viewing angle, the capacity for both reading and writing, better illumination, a wider field of view, variable power and magnification, and a longer working distance. The four new stand magnifiers are a spherical mirror magnifier, a cylindrical mirror magnifier, a reflecting prism magnifier, and a zoom magnifier. These magnifiers were tested on 39 subjects from five low vision clinics and compared to a commercial stand magnifier. The study determined reading speed and subject preference for these magnifiers. RESULTS: The reading speed of subjects with the new magnifiers increased over time and there was a significant change in preference over time. Results showed that 29 out of the 39 subjects on the final day of testing picked one of the new magnifiers as their device of choice. Reading speeds were comparable overall on all devices except for the cylindrical magnifier which was somewhat less. CONCLUSIONS: These four new ergonomically designed magnifiers were preferred by low vision patients compared to a commercial stand magnifier. PMID- 7884139 TI - Low vision aids training in the home. AB - BACKGROUND: In a continuing effort to better serve the low vision community, The Center for the Partially Sighted has developed an in-home low vision aids training (LVAT) program. Of interest to anyone working in the field of low vision is a description of our training materials and methodology, and a discussion of the efficacy of this program. METHODS: The previous literature on low vision was evaluated and organized into an orderly program geared toward the visual rehabilitation of low vision patients. RESULTS: Implementation of LVAT in the home began as a pilot project directed toward patients with macular degeneration who have begun reading as a primary goal of rehabilitation. CONCLUSIONS: Successful vision rehabilitation with low vision devices can be accomplished with proper training. Typically the exam does not allow ample opportunity to ensure that a patient is proficient in the use of a device. Follow-up training in the home environment may provide the necessary intervention to maximize patients' comfort and efficiency with low vision devices and their ability to accomplish near point tasks. PMID- 7884140 TI - Visual rehabilitation in low vision patients with aging macular degeneration. AB - Using optical visual aids, visual rehabilitation was performed in 14 cases (25 eyes) for low-vision patients with aging macular degeneration (AMD). With distance aids, visual acuity improvements were recorded for 24 eyes (95 percent) out of 25 eyes. Twelve eyes (48 percent) achieved vision equal to or better than 0.4. Utilizing near visual aids, the near visual acuity for all eyes (100 percent) were improved. Thirteen eyes (52 percent) received near vision equal to or better than 0.5. Ten patients were able to read No. 5 equal to or better than 0.5. Ten patients were able to read No. 5 Chinese print (corresponding visual angle is 0.67 at 30 cm of reading distance). The reading success rate was 71.4 percent. The results suggest that the application of visual aids is an effective method to improve the distance and near visual acuity of low vision patients with AMD. PMID- 7884141 TI - The introduction of new condensing lenses for fundus examination. AB - BACKGROUND: Examination of the inner eye is an important part of any comprehensive eye examination. There are a number of instruments used for examination of the ocular fundus; each has its advantages and disadvantages. Many of these instruments rely on hand-held lenses of which there are a number of options. METHODS: A doublet design lens consisting of two aspheric, plano-convex lenses, which have their convex sides facing toward each other and are separated by an air space, was evaluated and compared with other commercially available condensing lenses. RESULTS: A + 13.5 and +16 diopter doublet lens can be a valuable lens for binocular indirect ophthalmoscopy when compared with currently available, commercially available lenses. CONCLUSIONS: Innovative designs in lenses used with binocular indirect ophthalmoscopy may add considerably to the enhancement of the examination of the ocular fundus. PMID- 7884142 TI - Retention of inhaled hexafluorocyclobutene in the rat. AB - Hexafluorocyclobutene (HFCB), a cyclic analogue of perfluoroisobutene (PFIB), is a reactive gas that induces a fulminating pulmonary oedema in rats from which animals may die after an apparently asymptomatic period between 24 and 30 h, depending on the dose. To determine the dose of inhaled gas to the respiratory tract, the retention of HFCB has been determined in the rat at three inhaled concentrations with simultaneous measurement of respiratory parameters. Rats exposed continuously to HFCB retained 25%, 19% and 16% of the inhaled dose after exposure to 1.2, 6 and 30 ppm, respectively, which fell to 24%, 17% and 9% at 30 min and 21%, 16% and 6.5% after 1 h. The rate of uptake of HFCB decreased markedly at the highest concentration from 200 to 112 nmol min-1 kg-1 after 30 min and to 90 nmol min-1 kg-1 after a further 30 min. Ventilatory parameters were unchanged throughout the experiment and there was no evidence of pathological or histopathological damage at the end of the exposure. On renewal of exposure to gas after a 15-min pause, the percentage of gas retained was unchanged from that determined previously. The results indicate that there is a saturable component within the respiratory tract that is both time and concentration dependent. Hexafluorocyclobutene does not produce direct pathological damage outside the lung, which indicates that it may react rapidly with tissue components within the lung. PMID- 7884143 TI - Effects of atrazine on reproductive performance in the rat. AB - The effects of subacute exposure to atrazine on body weight, ovarian cycling, conception rate and the size of litters in Fischer strain rats were studied. An atrazine dose of 120 mg kg-1 body wt given p.o. daily for 7 days to both female and male rats caused statistically significant loss of body weight in both sexes during the period of treatment. After the cessation of treatment the body weight of female rats remained below control body weights at least for 2 weeks. In male rats the difference in body weights narrowed with time and reached control level 5 days after the last dose. Atrazine caused a significant increase in the relative weights of pituitary and prostate. Atrazine also transiently prolonged the oestrous cycle, characterized by extended vaginal dioestrus. As a result of disturbed ovarian cycling, the rate of successful mating decreased in the first week after treatment when both sexes were exposed or exposed females were mated with an unexposed male. No similar effect was observed when only the males were exposed. The size of litters did not differ significantly between experimental groups. PMID- 7884144 TI - Comparison of the sensory irritation response in mice to chlorine and nitrogen trichloride. AB - The expiratory bradypnoea indicative of upper airway irritation in mice was evaluated during a 60-min oronasal exposure to increasing concentrations of chlorine and nitrogen trichloride. The airborne concentration resulting in a 50% decrease in the respiratory rate of mice (RD50) was calculated for each chemical. Chlorine and nitrogen trichloride showed dissimilar concentration-response curves. While the maximal response of nitrogen trichloride was reached in 10 min, the maximal response of chlorine was reached between 45 and 60 min of exposure. The results showed both chemicals to have an irritant potency of the same order of magnitude. The RD50 values of chlorine and nitrogen trichloride were 3.5 and 2.5 ppm, respectively. On the basis of a TLV-STEL (threshold limit value for short-term exposure limit) equal to 0.1 RD50 and a TLV-TWA (time-weighted average) equal to 0.03 RD50, the current TLVs for chlorine seem too high (1 and 0.5 ppm, respectively) and should be reduced to 0.5 and 0.1 ppm, respectively. For nitrogen trichloride, 0.3 ppm and 0.1 ppm are proposed as TLV-STEL and TLV TWA, respectively. PMID- 7884145 TI - Toxicological evaluation of 1-chloroacetophenone and dibenz[b,f]-1,4-oxazepine after repeated inhalation exposure in mice. AB - Toxicological evaluation was made on the effects of two peripheral sensory irritants (tear gases): 1-chloroacetophenone (CN) and dibenz[b,f]-1,4-oxazepine (CR). Animals had a 15-min daily inhalation exposure to average vapour concentrations of 87.6 mg CN m-3 or 1008 mg CR m-3 (both equal to 0.05 LC50) for 5 or 10 days and were sacrificed 24 h after the last exposure, when biochemical and histopathological observations were made. Both chemicals caused a significant decrease in body weight gain. Histological changes in lung, liver and kidneys were more severe after 10 than after 5 days of exposure and were more severe in CN-exposed than in CR-exposed mice. Organ weight to body weight ratios remained normal except for the spleen to body weight ratio, which decreased in CN-exposed mice after both 5 and 10 days of exposure. Biochemical indicators showed a toxic response only in CN-exposed mice, but the only consistent change was an increase in blood glucose. Hepatic alkaline phosphatase was not influenced, malondialdehyde concentration and acid phosphatase activity were increased only after 5 days of exposure and liver GSH concentration decreased after 10 days of exposure. Results indicate that CN is not only more toxic than CR in absolute terms but is also more toxic at the 5% level of their LC50. PMID- 7884147 TI - Role of lipid peroxidation in biliary obstruction in the rat. AB - There is poor evidence about the participation of lipoperoxidative processes in liver damage induced by biliary obstruction, thus the aim of this work was to study the role of lipid peroxidation in this model of liver injury. Biliary obstruction was induced in male Wistar rats by ligation of the common bile duct; control animals were sham operated. Rats were sacrificed at different times after surgery. Liver sections were used for glycogen and lipoperoxidation quantification. Markers of liver damage were determined in serum. All serum markers of liver damage increased after 1 day of biliary obstruction. Liver glycogen content decreased 1 day after surgery. On the other hand, lipoperoxidation increased later than markers of liver damage, suggesting that it is a consequence rather than the cause of liver injury. Moreover, administration of colchiceine (a good free-radical scavenger) or vitamin E prevented lipoperoxidation but not liver damage, confirming that lipoperoxidation does not play an important role in liver damage induced by biliary obstruction. This model of liver injury seems to be useful for testing hepatoprotective drugs that do not act as free-radical scavengers. PMID- 7884146 TI - Effect of chemical form, route of administration and vehicle on 3,5 dichloroaniline-induced nephrotoxicity in the Fischer 344 rat. AB - Chloroanilines are widely used chemical intermediates for the manufacture of dyes, agricultural chemicals and industrial compounds. Nephrotoxicity occurs as one toxicity following intraperitoneal (i.p.) administration of chloroaniline hydrochlorides to rats. The purpose of this study was to examine the effect of chemical form, route of administration and vehicle on 3,5-dichloroaniline-induced nephrotoxicity. In one set of studies, male Fischer 344 rats (four to eight per group) were administered a single i.p. injection of 3,5-dichloroaniline free base or hydrochloride salt, cysteine hydrochloride or ornithine hydrochloride (0.8, 1.0 or 1.5 mmol kg-1) or an appropriate vehicle and renal function monitored for 48 h. Only 3,5-dichloroaniline hydrochloride induced nephrotoxicity that was characterized as acute renal failure. When 3,5-dichloroaniline free base (0.8 mmol kg-1) was administered in dimethyl sulfoxide (DMSO), all rats died within 24 h. In a second experiment, the free base or hydrochloride form of 3,5 dichloroaniline (1.5 mmol kg-1) or vehicle (0.9% saline or sesame oil, respectively) were administered orally and renal function monitored for 48 h. No evidence of nephrotoxicity was observed following either treatment. However, when the hydrochloride salt was given in 25% DMSO in 0.9% saline, all rats died within 24 h, with two rats demonstrating increased proteinuria, glucosuria and hematuria within the first 6 h after treatment. These results demonstrate that 3,5 dichloroaniline nephrotoxicity is potentiated by the administration of systemic acid, but that acid alone has no effect on renal function at the dose tested. Also, 3,5-dichloroaniline (hydrochloride or free base form) is less toxic orally than when administered i.p.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884148 TI - Time-dependent effects of lead on rat reproductive functions. AB - The effects of exposure to lead on endocrine function and the reproductive parameters were studied in pubertal rats treated with 1.0 g l-1 lead acetate in drinking water for 20 days (subacute group) or 9 months (chronic group) in addition to i.v. injections of lead acetate (0.1 mg 100 g-1 body wt.) every 10 (subacute group) or 15 days (chronic group). Although basal levels of testosterone were higher both in plasma and in testes of acutely intoxicated animals, the circulating levels of luteinizing hormone (LH) were not affected in either group, nor was the LH-releasing hormone content of the median eminence. The density of [125I]LH/human chorionic gonadotrophin (hCG) binding sites in testicular homogenates was reduced by saturnism in both groups, concomitant with a significantly increased apparent affinity constant of the hormone-receptor complex. These data can be viewed as the result of a mixture of specific lead toxicity (e.g. at the enzyme level) with other more general actions (e.g. at the level of the hypothalamus-pituitary-testicular axis). PMID- 7884149 TI - Toxicological evaluation of mu-agonists. Part I: Assessment of toxicity following 30 days of repeated oral dosing of male and female rats with levo-alpha acetylmethadol HCl (LAAM). AB - This study evaluated levo-alpha-acetylmethadol hydrochloride (LAAM), a long acting morphine-like (mu) agonist approved in 1993 to treat opiate dependence. Sprague-Dawley rate (20/sex/group) were gavaged with doses of 3.0-33.5 mg kg-1 for 30 days followed by a 14-day drug-free recovery period. Treatment-related effects included dose-dependent CNS depression, decreased food consumption and body weight gain, reddish urine and abdominal staining. Tolerance developed by day 7. Mortality was dose-dependent; deaths occurred predominantly during the first week. Increased alanine aminotransferase (SGOT, AST) and lactate dehydrogenase (LDH), observed only in high-dose males, were associated with findings in liver. Decreases in spleen/brain weight and increases in brain/body weight ratios were seen in both sexes. Decreases in weights of heart, liver and kidney achieved statistical significance only for high-dose groups. Kidneys of mid- and high-dose groups displayed intertubular mineral/crystal deposition, focal corticomedullary mineralization and focal regenerative tubular epithelium. Centrilobular hypertrophy was observed in livers of high-dose males and mid- and high-dose females. Following the recovery period, decreased body weights and increased brain/body weight ratios occurred in mid-dose males and low-dose females. Weights of liver and kidney and organ/brain weight ratios were decreased in mid-dose males. Histopathological findings observed in kidneys and livers had abated. In summary, acute and repeated administration of LAAM produced a spectrum of activity consistent with its profile as a long-acting pure mu-agonist which stimulates microsomal enzymes in rodents. Renal and hepatic effects seen in initially drug-naive rats treated with morphine-type agonists are not observed in tolerant individuals stabilized on mu-agonists to treat opiate dependence. PMID- 7884150 TI - Pathological mechanisms of hepatic tumour formation in rats exposed chronically to dietary hexachlorobenzene. AB - The chronic dietary administration of hexachlorobenzene (HCB) to rats for a year or more results in the formation of liver tumours described as hepatocellular carcinomas, hepatomas or haemangiomas. The hepatotoxicity of HCB, which is greatest in hamsters and rats, gives rise to peliosis and necrosis with haemosiderosis. This pattern of hepatotoxicity indicates vascular damage, which through haemosiderosis could increase not only the toxic effect of HCB to hepatocytes but also its tumourogenic potential. The present study confirmed vascular damage by the identification of widespread fibrin deposits in the livers of rats chronically exposed to HCB, using an antibody to rat fibrin. Based on our study we suggest that the formation of hepatomas and haemangiomas with elements of peliosis (cystic blood-filled cavities) could be explained by the compensatory hyperplastic responses to hepatocellular necrosis and by the simultaneous loss of hepatocellular cords. The accumulation of iron in the liver would strongly potentiate the development of hepatic tumours, as has been found in HCB and polychlorinated biphenyl-treated mice with iron overload. The implications of this non-genotoxic mechanism of hepatoma formation for the assessment of human health risk are discussed. PMID- 7884151 TI - Determination of free malonaldehyde formed in liver microsomes upon CCl4 oxidation. AB - Free malonaldehyde formed in the microsomes prepared from livers of monkey, rat, rabbit, mouse, cow, pig, dog, sheep and horse upon CCl4 oxidation was derivatized by reaction with N-methylhydrazine to form 1-methylpyrazole which was subsequently analyzed by capillary gas chromatography. Among the livers from animals tested, the monkey and rat livers produced the most malonaldehyde upon CCl4 treatment. Horse liver showed the greatest resistance to CCl4 oxidation. The gas chromatography method used in the present study exhibited an accurate and specific measurement of free malonaldehyde that might provide an understanding of the biochemical process of in vitro lipid peroxidation. PMID- 7884152 TI - Effect of an intracerebroventricularly administered vasopressin V1 antagonist on blood pressure and heart rate in deoxycorticosterone-salt hypertensive rats. AB - It is well known that peripheral vasopressin (VP) is essential for the development and maintenance of DOC-salt hypertension. It is, however, still unclear whether central VP is involved in this type of hypertension. Therefore, the aim of this study was to clarify the role of central VP in the regulation of blood pressure in DOC-salt hypertension. In order to examine this issue, three series of investigations were performed. First, a novel vasopressin V1 antagonist (OPC21268) was administered intravenously to DOC-salt hypertensive rats, and mean arterial blood pressure (MABP) and heart rate (HR) were recorded. Second, the concentration of VP in the perfusate of microdialysis of cerebrospinal fluid (CSF) was determined in DOC-salt hypertensive and control rats. Finally, intracerebroventricular (i.c.v.) administration of a V1 antagonist was performed in DOC-salt hypertensive rats to determine the central mechanism of hypertension. Intravenous administration of a V1 antagonist had no effect on MABP and HR. There was no difference in VP in the perfusate of CSF between DOC-salt hypertensive and control rats. I.c.v. administration of a V1 antagonist significantly decreased MABP and HR in a dose-dependent manner in DOC-salt hypertensive rats (P < 0.05 0.01). These results suggest that central VP is involved in the maintenance of DOC-salt hypertension, and the mechanism is, in part, mediated by upregulation of the V1 receptor. PMID- 7884153 TI - Vagal efferent nerve-dependent inhibitory action of pancreatic polypeptide and peptide YY in conscious rats: comparison with somatostatin. AB - The release of pancreatic polypeptide (PP) and peptide YY (PYY) is regulated by the vagal nerve, and the inhibitory effect of these peptides on pancreatic exocrine secretion shows indirectly via a neural mechanism. To determine the role of the vagal nerve on the inhibitory action of these peptides on the pancreas, we compared the effect on the pancreatic response to bile and pancreatic juice diversion in conscious rats with and without vagotomy. We also studied this response in rats treated with capsaicin, because bile-pancreatic juice diversion is the most potent endogenous stimulation of pancreatic secretion in conscious rats. In addition, since somatostatin potently inhibits of pancreatic enzyme secretion, the effects of PP and PYY were compared with somatostatin. An intravenous infusion of 2.5 nmol/kg per h of PP and PYY significantly inhibited the pancreatic responses of bile and pancreatic juice diversion in animals with an intact vagal nerve and in those treated with capsaicin, whereas the same dose of peptides failed to inhibit pancreatic secretion in vagotomized rats. Somatostatin inhibited pancreatic secretion under all conditions tested. We concluded that the inhibitory action of PP and PYY on pancreatic secretion is fully mediated by the vagal efferent nerve although other multiple mechanisms are involved for the inhibitory action of somatostatin. PMID- 7884154 TI - Alpha 1B-receptors and intracellular calcium mediate sympathetic nerve induced constriction of rat irideal blood vessels. AB - The present study has investigated the receptors involved in the non-cholinergic nerve mediated constriction of the larger blood vessels (30-50 microns) within the rat iris. This response was blocked by the alpha-adrenoceptor antagonist, benextramine (10(5) M). Furthermore, the response was more sensitive to blockade by the alpha 1 antagonist, prazosin (IC50 9 x 10(-10) M), than to blockade by the alpha 2 antagonist, yohimbine (IC50 2 x 10(-7) M), or the adrenergic antagonist, WB4101 (IC50 2 x 10(-8) M), and was abolished by chloroethylclonidine (10(-5) M). These results suggest the involvement of alpha 1B-adrenoceptors. The nerve mediated constriction was not blocked by the voltage-dependent calcium channel blocking drugs, nifedipine (10(-6) M), verapamil (10(-6) M) or diltiazem (10(-6) M), but was completely abolished by the intracellular calcium mobilizer, caffeine (10(-3) M), supporting the hypothesis that alpha 1B-adrenoceptors are activated following nerve stimulation. Dantrolene (10(-4) M), which interferes with calcium release from the sarcoplasmic reticulum, reduced the nerve mediated constriction by 40% as did thapsigargin (2 x 10(-6) M), which inhibits the calcium ATPase responsible for uptake of calcium into intracellular stores. When influx of calcium was blocked by verapamil (10(-6) M), thapsigargin, but not dantrolene, completely abolished the response. Noradrenaline (10(-5) M) produced a vasoconstriction in the presence or absence of external calcium although the latter response was significantly smaller than the former. Vasoconstriction produced by a submaximal concentration of noradrenaline (10(-6) M), was completely prevented by pretreatment with chloroethylclonidine. The data indicate that noradrenaline released from sympathetic nerves causes a constriction of arterioles in the iris by activating alpha 1B-adrenoceptors and releasing calcium from dantrolene sensitive and insensitive intracellular stores, followed by inflow of calcium through verapamil sensitive calcium channels. Applied noradrenaline also activates chloroethylclonidine sensitive receptors on the arteriolar surface. PMID- 7884155 TI - Regulation of the descending relaxation phase of intestinal peristalsis by PACAP. AB - The presence of pituitary adenylate cyclase-activating peptide (PACAP), a homologue of vasoactive intestinal peptide (VIP), in enteric neurons suggests that it may involved in the regulation of the descending relaxation phase of the peristaltic reflex. The role of PACAP was evaluated by measurement of PACAP release and by immuno-neutralization with specific monoclonal antibodies to PACAP 27 and PACAP-38, and an antibody to VIP. Electrical field stimulation at 4 Hz caused a 12-fold increase in PACAP release that was inhibited by 53 +/- 6% (P < 0.01) by the nitric oxide synthase inhibitor, NG-nitro-L-arginine (L-NNA). Orad stretch of colonic segments elicited descending relaxation and PACAP release in proportion to the degree of stretch. PACAP release induced by 10-g stretch was inhibited by 67 +/- 10% (P < 0.01) by L-NNA. Previous studies (Am. J. Physiol., 264 (1993) G334-G340) showed that orad stretch elicits also VIP release and nitric oxide (NO) production and that VIP release is inhibited (59%) by L-NNA. Preincubation of the segments with PACAP-27 plus PACAP-38 antibodies (50 micrograms/ml each), or with VIP antibody (1:60) inhibited descending relaxation at all degrees of stretch (inhibition with PACAP antibodies: 90 +/- 8% with 2-g and 22 +/- 5% with 10-g stretch). Preincubation with both PACAP and VIP antibodies virtually abolished descending relaxation. A similar pattern was observed with the antagonists, PACAP6-38 and VIP10-28, alone and in combination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884156 TI - Extensive distribution of NADPH diaphorase activity in the nerve supply of the cat lower urinary tract. AB - Nitric oxide is a neurotransmitter which causes smooth muscle relaxation and may contribute to this response in some regions of the lower urinary tract. In the present study the distributions of neurons and their axons which contain the synthetic enzyme for nitric oxide, nitric oxide synthase, were mapped by staining for NADPH diaphorase in sections of proximal urethra, bladder trigone and detrusor and whole mounts of vesical ganglia from cats. Stained axons were present in the smooth muscle of all regions of bladder and proximal urethra, but were most common in the urethra and least prevalent in the detrusor. Stained axons were also present in the mucosa; most of these were associated with blood vessels, but some travelled close to the epithelium. Stained mucosal axons were much more numerous in the proximal urethra than in any bladder region. Darkly stained neuronal somata were found throughout the vesical ganglia, where they appeared to comprise the majority of neurons. Small ganglia containing stained neurons were also found in sections of various urinary tract regions, where they were located in the serosa, between muscle layers and, in the urethra, also in the mucosa. These studies have shown an extensive distribution of neurons and axons that stain for NADPH diaphorase (and are predicted to synthesize nitric oxide) throughout all tissues of the cat lower urinary tract. It is hypothesized that nitric oxide is an inhibitory transmitter in the cat bladder and proximal urethra and may also have a role as a sensory transmitter in the mucosa of these regions. PMID- 7884157 TI - Instrumentation of ramus circumflexus compromises the innervation of coronary artery and myocardium. AB - A fine non-compressing methacrylate ring was implanted on the ramus circumflexus (RC) in 13 dogs. After the animals survived 7-14 days, the distribution and the rate of the Wallerian degeneration was studied in coronary arteries and myocardium by means of the formaldehyde induced fluorescence (FIF) technique and the transmission electron microscopy. The density of vasomotor innervation in the main arterial trunks was expressed as the number of transsected terminals per 1 mm2 of the transversally sectioned media; the density of adrenergic terminals in the myocardium was determined by the point-counting method. A compact scar encompassing the ring was found. The scar compressed some perivascular nerves. As a consequence, by about 40% of terminals degenerated in the RC. The innervation of the branching of this artery was compromised as well. Moreover, the density of nerve terminals in myocardium decreased around the whole circumference of the ventricles and in the septum, equally by 29%. The value was lower than that found after the instrumentation of ramus interventricularis anterior (50%). The results indicate (i) a compromise of the innervation of coronary artery and myocardium after the instrumentation of RC; (ii) the different decrease in density of nerve terminals in the myocardium suggests that majority of adrenergic nerve supply for ventricle myocardium is running along ramus interventricularis anterior. PMID- 7884158 TI - Comparison of the postural tachycardia syndrome (POTS) with orthostatic hypotension due to autonomic failure. AB - Postural tachycardia syndrome (POTS) is characterized by orthostatic dizziness, tremulousness, tachycardia and variable blood pressure changes. Since some POTS patients have a marked reduction in pulse pressure on standing, a major mechanism of their symptoms might be venous pooling. We therefore studied the cardiovascular response to head-up tilt, Valsalva maneuver and deep breathing in: control subjects (n = 11; F = 8; M = 3; 39.2 +/- 14.4 years); patients with orthostatic hypotension secondary to autonomic failure (n = 11; F = 9; M = 2; 61.7 +/- 13.0 years), and patients with POTS (n = 15); F = 13; M = 2; 32.3 +/- 10.6 years). Blood pressure was measured with a Finapres, and cardiac output, stroke volume, end-diastolic volume and thoracic impedance (TFI) were measured by thoracic electrical bioimpedance. During tilt (in contrast to patients with orthostatic hypotensiom), patients with POTS had excessive tachycardia (P < 0.001), a normal to excessive total peripheral resistance increase, and an exaggerated decrease in stroke volume (P < 0.001) and end-diastolic volume (P < 0.001). These findings suggest that sympathetic arteriolar function remains relatively intact but that sympathetic venomotor function is selectively impaired. These findings may have significant implications for the treatment of patients with POTS. PMID- 7884159 TI - H3 receptors: modulation of histamine-stimulated neural pathways influencing electrogenic ion transport in the guinea pig colon. AB - The role of H3 receptors in neurally-evoked recurrent increases in chloride ion secretion evaluated from changes in short-circuit current (Isc) was examined during application of histamine or histamine analogs. Muscle-stripped or whole thickness segments of distal colon were set up in flux chambers. Histamine and dimaprit, an H2 receptor agonist, caused recurrent increases in Isc. Dimaprit evoked recurrent responses were reduced by the H3 receptor agonists, N alpha methylhistamine and R alpha-methylhistamine, and the inhibition was reversed by the H3 receptor antagonist, burimamide. Histamine-evoked recurrent increases in Isc were enhanced by the H3 receptor antagonists burimamide and thioperamide. The results indicate that H3 receptors play an inhibitory role in histamine-evoked, neurally-mediated recurrent increases in Isc in guinea pig colon. PMID- 7884160 TI - Development of fear-related heart rate responses in neonatal rabbits. AB - Classical simple conditioning of heart rate (HR) was studied in rabbits between the 1st and 18th neonatal day. An auditory stimulus (1000 Hz, 5 s) served as the conditioned stimulus (CS), and a train of electric impulses (100 Hz, 500 ms, 1 1.5 mA) was used as the unconditioned stimulus (US). HR responses developed during orientation session (CS-alone) as well during acquisition (CS-US paired) were analyzed and compared to those developed by young adult rabbits (3-month old). In all neonatal animals tested, baseline HR measured during an adaptation session preceding conditioning, was similar though significantly higher than that measured in adult rabbits (Newman-Keuls P < 0.05). Before the 10th neonatal day, the animals did not show either somatomotor or HR orienting responses to the CS alone presentations. Consequently, since orienting reactions play a necessary role in the formation and manifestation of conditioned reflexes, 1 to 10-day-old infant rabbits were not submitted to the acquisition session. All the other neonatal groups, while showing orienting behaviours similar to those exhibited by adults (head and pinna movement), presented different patterns of HR orienting responses (no response, bradycardia, tachycardia, bradycardia/tachycardia etc.). As for the acquisition session, the first bradycardic response, similar to that developed by adult rabbits, was found in 18-day-old rabbits. However, also in this neonatal group the amplitude of the conditioned response was significantly smaller when compared to that exhibited by young adults (Newman-Keuls P < 0.01). In addition, in some of the 10-day-old neonates, HR appeared very unstable and dropped to very low values (as low as 146 beats/min) early during conditioning, apparently as a consequence of CS-US association. As for the unconditioned response, no differences were found between adult rabbits and the neonatal animals older than 12 days. In contrast, most of the 10-day-old rabbits showed either bradycardia or no response to the unconditioned stimulus. Considering the ability of mammalian infants to learn somatomotor conditioned responses at early stages of maturation, conditioning of HR responses occurs late during ontogeny. Since this incapacity to show HR conditioned responses before the 18th postnatal day cannot be ascribed to their inability to show phasic HR changes nor to a failure in detecting the auditory stimulus, these results suggest the possibility that HR conditioned responses may be mediated by neural structures developing later during maturation. PMID- 7884161 TI - Elders vulnerable to telemarketing fraud and abuse. PMID- 7884162 TI - Postcardiac-event elderly: effect of exercise on cardiopulmonary function. AB - 1. The findings of this study contradicted those of previous studies in the areas of respiratory rates, conditioning, and the effect of exercise on diastolic blood pressure. 2. This study indicates that the heart's requirement for oxygen at a given MET load (a unit of energy cost-related to workload) is significantly reduced in elderly cardiac-event patients following a 6-week conditioning program; thus, a similar program would appear to provide cardioprotective effects to this population. 3. This study demonstrated that, as a result of physical conditioning, heart rate, systolic blood pressure, and rate-pressure product showed significant beneficial reductions which would allow elderly postcardiac event patients to function more effectively in daily activities. PMID- 7884163 TI - Quality of life: its meaning to the long-term care resident. AB - 1. While the physical and recreational environments have been shown to be important to the mental health of the long-term care resident, human relationships and social contact have been described as being far more important in determining quality of life. 2. This study identified two new findings as contributing to quality of life--caring for oneself and the importance of helping others. 3. Failure to accurately assess a resident's ability to provide self-care may lead to excess disability, a situation in which a resident may become more functionally disabled, in part, due to the staff performing more care than is actually needed. PMID- 7884164 TI - A nursing protocol to assess causes of delirium. Identifying delirium in nursing home residents. AB - Because delirium is often a harbinger of underlying physical illness in frail elders--which can cause further morbidity and functional decline--it is essential to accurately assess the causes of delirium. Nurses working in nursing homes are in the best position to make these assessments and advocate for the appropriate management of delirium. The implementation of the proposed nursing protocol may empower nurses and, thus, improve outcomes of nursing home residents suffering from delirium. PMID- 7884165 TI - Social support. Among elderly in two community programs. AB - Elderly individuals lacking adequate social support have shown greater deficits and difficulties in illness recovery, length of hospitalization, and development of cognitive and emotional changes than those who do receive adequate social support. This study evidenced a very meaningful finding for nurses--older adults who are often dependent upon others for support in some or most facets of daily living specified love and respect as the type of support most needed, rather than tangible aid. In most communities, a wide array of educational and support group programs are offered to older adults. Social networking and the enhancement of social support among participants should be primary goals of such programs. PMID- 7884166 TI - Use of restraints; changes in nurses' attitudes. AB - Patients can become more agitated after the application of restraints. Restraints may be necessary to prevent injury to patients. Diversions, presence of family members, recliner chairs, day rooms, or sitters are alternatives to physical restraints. PMID- 7884167 TI - Wound and skin team. Impact on pressure ulcer prevalence in chronic care. AB - 1. Decreasing the prevalence of pressure ulcers in a chronic care hospital presents a challenge to care providers. 2. The promotion of staff nurses as educational resources has a positive effect on their participation in a wound and skin care team. 3. When basic prevention practices are not in place, risk factors are less useful indicators to predict the development of pressure ulcers. 4. Educating nurses about pressure ulcer etiology, prevention strategies, and treatments has a positive impact on reducing the number of patients who develop pressure ulcers and the number of pressure ulcers that develop on patients in a chronic care hospital. PMID- 7884168 TI - Meeting the needs of home caregivers: a family caregiver checklist. PMID- 7884169 TI - Triple therapy eradicated H. pylori equally in patients pretreated with omeprazole or ranitidine. A 12-month follow-up. AB - The aim of this study was twofold: first, to investigate the effectiveness of a standard triple therapy (tripotassium dicitrato bismuthate, 125 mg q.i.d., tetracycline hydrochloride 500 mg q.i.d., and metronidazole 500 mg t.i.d.) in eradicating Helicobacter pylori in patients with duodenal ulcer successfully healed with omeprazole or ranitidine; second, to examine the influence of the eradication on duodenal ulcer recurrence rate after 12 months. Two hundred forty five consecutive H. pylori-positive patients with healed duodenal ulcer either with omeprazole (20 mg/day, 126 patients) or with ranitidine (150 mg b.i.d., 119 patients) given at random, began triple therapy for 15 days. H. pylori eradication was looked for 4-5 weeks later by culture of biopsy material, hematoxylin-eosin stain, and rapid urease test. H. pylori-eradicated patients were followed up for 12 months. Endoscopy was carried out at the end of the follow-up or whenever symptoms appeared. Five patients (2.0%) withdrew because of triple-therapy-related side effects. The eradication rate was 92% (220 of 240 patients); no difference was found between those healed with omeprazole (93%, 114 of 123 patients) or ranitidine (91%, 106 of 117 patients). Of 220 successfully treated patients, 132 completed the 12-month follow-up. The duodenal ulcer recurrence rate was 4% (5 of 132 patients); 3% (2 of 70) in the omeprazole group and 5% (3 of 62) in the ranitidine group healed. All the recurrences were asymptomatic. H. pylori recurrence rate was 11% (14 of 132 patients); no difference was found between patients healed with omeprazole (10%, 7 of 70 patients) or with ranitidine (11%, 7 of 62 patients). All the recurrent duodenal ulcers occurred in H. pylori-positive patients (36%, 5 of 14 patients). Standard triple therapy after duodenal ulcer healing with omeprazole or ranitidine eradicates H. pylori in comparable high rates. Side effects were mild and dropouts were only 2%. Ulcer recurrence rate 12 months after eradication was low and comparable between those healed with omeprazole or ranitidine. PMID- 7884170 TI - Comparison of serum anti-gliadin, anti-endomysium, and anti-jejunum antibodies in adult celiac sprue. AB - We compared the diagnostic accuracy of a new immunological marker of celiac sprue (CS), the antijejunum antibody (JAB), with that of antigliadin (AGA) and antiendomysium (EmA) antibodies. One hundred untreated adults with biopsy-proven CS, 52 healthy controls, and 57 patients with inflammatory bowel disease, lymphoma of the small bowel, Whipple's disease, and irritable bowel syndrome were investigated. Only JAB and EmA were detected at a similar titer in all patients with untreated CS but in no controls (100% sensitivity and specificity). Sensitivity of AGA was, respectively, 55% for IgA and 78% for Ig class, with a 100 and 82% specificity. The differences in frequencies between both EmA and JAB with IgA and IgG AGA were highly significant. We conclude that JAB and EmA provide a reliable noninvasive screening test for clinically significant gluten sensitive enteropathy. The lower cost of IgA-JAB is a major advantage, owing to the different availability of the lower third of the esophagus and jejunum from primates. The sensitivity and specificity of the two tests are almost identical, but we find interpreting EmA easier than JAB especially when the titer is low. PMID- 7884171 TI - Is vagotomy and gastrectomy still justified for gastroduodenal ulcer? PMID- 7884172 TI - Death from Crohn's disease. Lessons from a personal experience. AB - We traced 1,000 patients with Crohn's disease hospitalized at Lenox Hill Hospital in New York City during 1972-1987 to identify those who died, the events preceding death, and their relationship to Crohn's disease. We considered any management early in the disease that might have influenced outcome. We introduce the term "virulent" Crohn's disease to describe those patients with most or all of the following: young age at onset, multiple surgical procedures, short bowel/malabsorption, chronic steroid therapy, narcotic addiction, and sepsis. Twenty-five patients (2.6%) had died. Major events preceding 18 deaths related to Crohn's disease were virulent Crohn's disease (six), gastrointestinal neoplasms (six), complications in the elderly (five), and complications of drug therapy (one). Those seven deaths probably unrelated to Crohn's disease were attributed to extraintestinal neoplasms (four) and myocardial infarction (three). Death was related to Crohn's disease or its treatment in 72% and perhaps in all. Ten of the 25 died at age 46 or younger (mean 36 years, range 25-46 years). Twenty-two (88%) who died had undergone surgery for Crohn's disease (mean 3.3 procedures) including eight who died postoperatively (six elderly), attributable to sepsis in seven and pulmonary embolism in one. The events preceding death suggest that early aggressive nonoperative therapy for severe Crohn's disease warrants a careful controlled evaluation. PMID- 7884173 TI - Usual therapy improves perianal Crohn's disease as measured by a new disease activity index. McMaster IBD Study Group. AB - Troublesome perianal disease occurs in approximately 35% of patients with Crohn's disease, yet conventional disease activity indices do not reflect the severity of this feature. To assess the degree of impairment and response to therapy, we identified five simple elements and graded each on a 5-point Likert scale in 37 patients at 124 visits. At each visit a Crohn's Disease (CDAI) or Simple Activity Index (HBDAI), Perianal Disease Activity Index (PDAI), and treatment were recorded. The PDAI was validated against physician (MDGA) and patient (PGA) global assessments, and treatment was prescribed for the perianal disease. Measurement error was evaluated in 19 patients who were clinically stable at two consecutive visits. The ability of the PDAI to detect important clinical change was tested in 20 subjects exhibiting a change on PGA at consecutive visits. There were strong correlations between PDAI, MDGA, and PGA scores at all visits (R = 0.66-0.72; p < 0.001), whereas the CDAI and HBDAI correlated poorly with PDAI (R < 0.23). Physicians prescribed more aggressive therapy for higher PDAI scores (r = 0.53). Mean PDAI scores between visits in clinically stable subjects were not significantly different [5.58 +/- 2.79 (initial); 5.42 +/- 2.55 (follow-up); p = 0.63]. PDAI significantly improved between visits when the perianal disease had improved (PDAI score difference 3.05 +/- 2.96; P = .0002). We conclude that the PDAI is simple and clinically useful for patient management. It should now be assessed in a clinical trial. PMID- 7884174 TI - Drinking habits and pain in chronic pancreatitis. AB - To study the role that continuous drinking plays in the pain of chronic pancreatitis, we have examined 67 patients with alcoholic chronic pancreatitis with pain and 29 patients without pain, and we report on their alcoholic habits. Drinking habits played a part 92 (67.6%) of 136 times in patients with pain; in 185 without pain, 86 (46.5%) had continued their drinking habit (p < 0.001). Advanced pancreatic exocrine insufficiency was seen in 27 patients; 11 of them had pain during follow-up, whereas 16 did not. The nondrinker rate was similar in patients with and without pain, whereas among 69 patients with better pancreatic exocrine function, 56 had pain episodes and 13 did not. Alcoholic consumers were significantly more in number in the pain group: 70.4% versus 35% of the no pain group (p < 0.002). Our study shows that drinking alcohol in patients with chronic pancreatitis increased the frequency of painful episodes when there was relatively good pancreatic function, whereas in severe pancreatic insufficiency drinking had less influence on the development of pain. PMID- 7884176 TI - Alcohol in chronic pancreatitis. Does it provoke the pain? PMID- 7884175 TI - Abstinence in alcoholic chronic pancreatitis. Effect on pain and outcome. AB - The role of alcohol in causing chronic pancreatitis is well-known, but the role of abstinence remains controversial and not well-understood. In this article, I examine the literature dealing with the effect of abstinence on chronic pain and the long-term outcome of chronic pancreatitis. A series of 50 patients with alcoholic chronic pancreatitis from my practice supplements the data. Alcohol consumption > 70 g/day for 7 or more years is characteristic. Moderate to severe abdominal pain is the dominant symptom. When patients stop drinking, abdominal pain disappears in the majority, pancreatic function deteriorates more slowly, the death rate diminishes, and a normal life is often possible. If abdominal pain continues after abstinence and the pancreatic duct remains dilated, a lateral pancreatojejunostomy helps most patients. In many patients not suitable for surgery, pain resolves with time. PMID- 7884177 TI - Raising the dose of interferon does not improve the response in chronic hepatitis C. AB - We report results of dose escalation to 5 or 6 million units (MU) three times weekly (t.i.w.) of interferon-alpha in 17 consecutive patients with chronic active hepatitis C who were not responding to 3 MU t.i.w. after > or = 12 weeks of therapy. The mean pretreatment alanine aminotransferase (ALT) level was 206 +/ 62 U/L and, at the time of dose escalation, 113 +/- 71 U/L. Two patients could not tolerate the dose escalation. The remaining 15 patients were treated for an additional 10 +/- 3.5 weeks. Three patients had a complete response 3-8 weeks after dose escalation. At the end of high-dose therapy, the mean ALT level was 105 +/- 76 U/L (n = 15). During the 6-month posttreatment follow-up time, the mean ALT level was 147 +/- 85 U/L. All three responders had a relapse. Increasing the dose of interferon-alpha to 5-6 MU t.i.w. in chronic hepatitis C patients who are not responding to interferon-alpha, 3 MU t.i.w., at the 12th week of therapy is unlikely to result in sustained normalization of ALT levels. PMID- 7884178 TI - Gastrocolic fistula secondary to primary gastric lymphoma. AB - Gastrocolic fistula in primary non-Hodgkin's lymphoma (NHL) of the stomach is rare; in a review of the literature we found only four cases, all in association with disseminated (stage IV) disease. We describe the first case of a gastrocolic fistula in a patient with stage IE lymphoma. The diagnosis was suggested by feculent vomiting, and the fistula was located using barium enema and CT scan. Therapy consisted of local resection followed by combination chemotherapy. PMID- 7884179 TI - A case of biliptysis. AB - A 76-year-old white woman with ovarian adenocarcinoma developed massive biliptysis following an unexpected respiratory arrest. The possibility of active right upper quadrant disease had not been entertained until she developed this complication of a biliobronchial fistula. Because this sign had not previously been observed by any of us, it led to a comprehensive review of the topic of biliobronchial fistula. PMID- 7884180 TI - Nortriptyline-induced fulminant hepatic failure. AB - We describe, to our knowledge, the first reported case of nortriptyline-induced fulminant hepatic failure. This tricyclic antidepressant drug was taken by a postmenopausal woman for 64 days before her presentation. The absence of fever, rash, or marked eosinophilia, the predominant zone 3 necrosis with bridging, and the latent period favor a metabolic idiosyncratic reaction. The fatal outcome underscores the importance of recognizing the association and discontinuing the offending agent. PMID- 7884181 TI - Hepatic involvement culminating in cirrhosis in a child with disseminated cryptococcosis. AB - A 7-year-old child had unusual manifestation of cryptococcosis; liver and lymph node involvement predominated. There was evidence of cryptococcal hepatitis, extrahepatic biliary obstruction, and subsequent cirrhosis of the liver. Despite widespread dissemination, underlying immune disturbance was not evident. The patient was treated with two courses of amphotericin and 5-flucytosine. PMID- 7884182 TI - Reflux in untreated achalasia patients. AB - We made a prospective assessment of acid exposure in the distal esophagus in 48 consecutive untreated patients with achalasia using 24-h ambulatory esophageal pH studies. The majority of patients (38/48) experienced reflux that was within reported values for normal controls (total time pH < 4.0, 1.8 +/- 1.9%). Approximately 20% (10/48), however, demonstrated abnormal acid exposure (total time pH < 4.0, 18.8 +/- 14.8%). The difference in reflux expressed by these two groups was not due to a significant difference in lower esophageal sphincter pressure (p > 0.05) or retained food. An in vitro model of lactobacillus fermentation supported the contention that true acid reflux accounted for changes in esophageal pH. Repeat pH studies were obtained in 23 patients following treatment: 15 underwent pneumatic dilatation and 8 underwent limited myotomy. Although no significant differences were found between pre- and posttreatment reflux, some patients undergoing either treatment were found to demonstrate increased acid exposure. In conclusion, we believe that patients with achalasia should be tested by pH study both before and after treatment. Most of the patients who demonstrated significant pretreatment reflux were asymptomatic, and both methods that were used to decrease resting sphincter pressure were shown to be able to increase distal acid exposure. PMID- 7884183 TI - Constipation and incontinence in the elderly. AB - We summarize the prevalence and causes of constipation and incontinence in an elderly, drawing particular attention to the roles of immobility, dietary fiber, and dehydration. The physiology of fecal impaction is described in detail, and neurological and mechanical causes (rectal prolapse, rectocele, and hemorrhoids) of constipation are discussed. Consideration is also given to constipation associated with diverticular disease and ulcerative colitis. We also discuss the pathogenesis of fecal incontinence in the elderly, paying particular attention to fecal impaction and neurological causes that result in both constipation and incontinence. The importance of previous obstetric trauma and pudendal enuropathy is emphasized. We conclude with detailed guidelines of the clinical assessment and management of an elderly patient with a disorder of defecation. PMID- 7884184 TI - Partial nodular transformation of the liver with portal vein thrombosis. A report of two autopsy cases. AB - Partial nodular transformation (PNT) of the liver is a rare condition in which nonfibrous nodules composed of hyperplastic hepatocytes replace the hepatic parenchyma around the hepatic hilus. We report two autopsy cases involving PNT of the liver with portal vein thrombosis. Case 1 was a 27-year-old man with malignant lymphoma. Ascites gradually increased, and he died 4 years after the onset of his illness. Case 2 was a 73-year-old woman treated for cirrhosis for 4 years who died of renal failure. Postmortem examination of these two cases revealed numerous coalescent nodules in the hilus of the liver as well as portal vein thrombus in the hilus. Microscopically, these nodules in the perihilar area were composed of hyperplastic hepatocytes without fibrous rim, and the peripheral parenchyma showed atrophy to some extent. The portal vein thrombi in the hilus and large portal tracts were mainly fresh and partially organized. Portal vein branches in the peripheral small portal tracts were devoid of significant pathologic changes. We suggest that PNT of the liver in our cases occurred as the result of uneven blood supply to the perihilar parenchyma due to portal vein thrombosis in the hepatic hilus. PMID- 7884185 TI - Endoscopic ultrasonography as a guide to strip biopsy removal of esophageal submucosal tumors. PMID- 7884186 TI - Intragastric fermentation in patients with gastroparesis diabeticorum. PMID- 7884187 TI - Acute proctitis after a hot-water enema. PMID- 7884188 TI - Gallbladder tuberculosis with perforation and intrahepatic biloma. PMID- 7884189 TI - Mesenteric ischemia due to an occluded superior mesenteric artery treated by percutaneous transluminal angioplasty. PMID- 7884190 TI - Benign retropneumoperitoneum induced by vomiting. PMID- 7884191 TI - Risk of human immunodeficiency virus infection for emergency department workers. Italian Study Group on Occupational Risk of HIV Infection. AB - To evaluate the risk of human immunodeficiency virus (HIV) exposure among emergency department workers (EDWs) and their ability to identify HIV-infected patients, a seroprevalence study was performed in March 1991 in the emergency departments (EDs) of six Italian urban hospitals. At each visit, patients aged 18 65 years were asked to undergo fingerstick blood sampling for anonymous, unlinked HIV testing performed on blood adsorbed filter paper collection cards. Demographic characteristics, known or suspected HIV risk factors, and occupational exposures reported by the EDWs during the patient's visit were recorded. On 9,457 consecutive visits, 9,005 samples (95%) were tested and 65 (0.7%) were HIV positive. ED staff failed to identify 59% of HIV-infected patients. The rate of occupational exposures was 0.13/100 visits. As it is impossible to predict the HIV status of patients attending EDs, adherence to universal precautions and the development of safer devices should be utilized to minimize the risk of blood-borne infections in EDWs. PMID- 7884192 TI - The management of sharps in the emergency department: is it safe? AB - In this study, we observed the management of sharps by health care workers including physicians, nurses, technicians, and students in the Emergency Department of the University of California-San Diego Medical Center. Twenty-eight percent of 418 observed sharp utilizations were managed in such a way that excess risk was conferred to the user, another person, or both. Twenty-seven percent conferred excess risk to the user and 12% to another person. Twenty percent of 322 recappable needles were recapped using a two-handed technique; 64% were disposed of uncapped. Four sharps (1%) were inadvertently thrown in the trash. Of the 418 observed sharp utilizations, none resulted in a puncture wound, although the four that were thrown in the trash represent a very high risk of injury to others. Physicians were observed handling the highest percentage of sharps in manners associated with excess risk while technicians and students managed sharps with the least risk. Among sharps used on patients who were IV drug abusers with unknown HIV status, 29% (n = 28) were handled with excess risk to the user, another person, or both. Of 24 sharps used on known HIV-infected patients, there were no practices observed that subjected either the user or another person to excess risk. PMID- 7884193 TI - Epidemiology and prevention of blood and body fluid exposures among emergency department staff. AB - Emergency Department (ED) staff are vulnerable to occupational exposure to infectious blood and body fluids (BBF). Universal precautions are often ignored in the ED setting. Identification of body locations at high risk of BBF exposure may allow development of site specific protective garments that minimize risk and inconvenience. All permanent staff (92) in a 58,000 visit public university hospital ED with potential for BBF exposure were surveyed. Respondents estimated the number of BBF contacts sustained during the past year, describing their most recent contact in detail. Seventy-eight of 91 (85%) responded, reporting average rates of 54.1 intact skin, 1.5 nonintact skin, and .87 mucous membrane BBF contacts per full-time employee per year. Of the most recent incidents, 94% involved blood, 22% involved vomit or urine, and 11% involved saliva. Eighty eight percent of BBF contacts were to unprotected skin or mucous membranes, either when no barrier was worn or at the gap between gloves and sleeves. Most (66%) were distal to the elbow; 13% involved the face. Use of long gloves or another continuous protective barrier from the fingers to the elbow, in addition to increased use of face masks or shields, would markedly reduce the rate of ED BBF contacts with a minimum of inconvenience. PMID- 7884194 TI - Plasma beta-endorphin levels and childhood intussusception. AB - To determine whether childhood intestinal intussusception is associated with elevated plasma beta-endorphin levels, a series of patients was studied prospectively. Fourteen patients (age range between 3 months and 7 years) presented to two university pediatric emergency departments in Chicago with clinical symptoms and signs of intussusception. Venous blood (2cc) was withdrawn for plasma beta-endorphin determination, followed by barium enema. Plasma beta endorphin levels were measured by radioimmunoassay. The mean beta-endorphin level of the 8 patients with barium enema proven intussusception was 14.1 +/- 12.0 pg/ml. Two of these patients presented with marked lethargy and had beta endorphin levels of 7.5 and 21.2 pg/ml. The mean plasma beta-endorphin level of the 5 patients with negative barium enema studies was 18.1 +/- 10.0 pg/ml (P = 0.56). A sixth control patient had a plasma beta-endorphin level of 1569 pg/ml. In conclusion, childhood intestinal intussusception is not associated with elevated plasma beta-endorphin levels. PMID- 7884195 TI - End-tidal carbon dioxide detection in emergency intubation in four groups of patients. AB - A prospective clinical trial was conducted at a level I trauma center to assess the efficacy of end-tidal carbon dioxide (CO2) detection in four groups of patients requiring emergency intubation because of cardiac arrest, major trauma, respiratory failure, or the need for airway protection. A semiquantitative, colorimetric FEF end-tidal CO2 detector (Fenem, Inc, New York, NY) was used to evaluate endotracheal versus esophageal intubation. This disposable, bedside detector registers three ranges of CO2 concentration: "A" (purple) indicates low levels and probable esophageal intubation; "B" (beige) indicates moderate levels and probable tracheal intubation with hypocarbia; "C" (yellow) indicates high levels and tracheal intubation. Clinical observation, patient response, chest x ray films, and arterial blood gas results were used to corroborate placement of the endotracheal tube. The FEF detector was found to be 100% reliable for confirming tracheal placement when registering levels in the B and C ranges and 100% reliable for detecting esophageal intubation when registering levels in the A range. In conclusion, the FEF CO2 detector is a reliable and useful adjunct for airway management of diverse groups of patients in the emergency setting. PMID- 7884196 TI - Acute diverticulitis in young adults. AB - Diverticular disease of the colon is generally considered a disease of older patients, rarely causing symptoms before age 40. Two recent cases of ruptured sigmoid diverticulitis in young female patients presenting to our Emergency Department prompted a review of the literature on this topic. Diverticulitis is more common in patients under 40 than previously suspected. Presented are the two cases and a brief summary of the literature review. PMID- 7884197 TI - Posterior sternoclavicular dislocation: a case report. AB - Posterior sternoclavicular dislocation is a relatively rare form of trauma, but one that must be recognized by the emergency physician. Such a case is presented here. Due to the proximity of the clavicle to critical thoracic outlet structures, serious complications can arise from a posterior dislocation: impingement on and possible trauma to the trachea, pneumothorax, laceration of underlying great vessels, brachial plexus injury, esophageal trauma, and laryngeal trauma that may cause permanent vocal cord changes. Many of these potential complications are life-threatening, and it is important that this injury not be triaged in the emergency department as a minor injury, thereby leading to its improper or delayed treatment. PMID- 7884198 TI - Spinal cord ischemia after cardiac arrest. AB - Subsequent to cardiac arrest, a 58-year-old man with intractable dysrhythmia and severe arteriosclerosis developed flaccid paraplegia, depressed deep tendon reflexes, and showed no pain or temperature sensation caudal to Th-7 in spite of completely intact proprioception and vibration sensation. An echocardiogram showed no clots or vegetation on the prosthetic valve and no thrombus in the left atrium or left ventricle. The patient's paraplegia was permanent, at least through a follow-up period of 2 years. These findings suggest that the etiology was spinal cord ischemia due to blood supply in the area of the anterior spinal artery (ASA); however, magnetic resonance T2-weighted imaging demonstrated signal abnormalities throughout the gray matter and in the adjacent center white matter. Somatosensory-evoked potentials (SEP) measure neural transmission in the afferent spinal cord pathway, which is located in the lateral and posterior columns of the white matter; these showed a delay in latency between Th-6 and Th-7. The spinal cord is as vulnerable to transient ischemia as the brain. Spinal cord ischemia after cardiac arrest results from principal damage in the anterior horn of the gray matter, the so-called ASA syndrome; however, the pathways of SEP and pathogenesis of the spinal cord ischemia need further investigation. PMID- 7884199 TI - Beta blocker toxicity after overdose: when do symptoms develop in adults? AB - Published reports of beta blocker ingestions in adults are retrospectively reviewed to determine at what point postingestion symptoms develop. Thirty-nine symptomatic beta blocker ingestions were found. The patients ranged from 14 to 67 years of age. Thirty-one (80%) of those who demonstrated symptoms did so within 2 h of ingestion. This number rose to thirty-eight (97%) by 4 h postingestion. Only one patient developed symptoms after more than 4 h of asymptomatic observation. The development of bradycardia and first degree atrioventricular block during observation appeared to predict toxicity in this patient who suddenly developed hypotension 6 h postingestion. No patient required treatment for delayed cardiovascular depression if they remained asymptomatic during a 4-h period of observation postingestion and demonstrated a normal electrocardiogram throughout. Whether the risk of delayed onset of toxicity after 6 h of asymptomatic observation is sufficiently low to warrant "medical clearance" requires further investigation. PMID- 7884200 TI - Maintenance fluids in prehospital care: crystalloid versus dextrose solutions--is there a difference? AB - D5W is the maintenance fluid often used in prehospital care when transporting patients with cardiac or central nervous system processes. However, there is evidence that dextrose solutions are potentially harmful, and that suggests isotonic crystalloid solutions are the preferred maintenance fluid in treating emergent patients regardless of their underlying disease. Dextrose solutions may exacerbate cellular ischemic damage and they cannot be used to resuscitate hypotensive patients. Crystalloids do not cause fluid overload when used at maintenance rates and are effective resuscitative agents in managing hypotension. The use of a single crystalloid solution in the prehospital environment would simplify equipment stocking and management protocols, minimize cost, and would not have an adverse impact on patient care. PMID- 7884201 TI - Disaster preparedness of home health care agencies in San Diego County. AB - A questionnaire was sent to 53 home health care agencies in San Diego to assess their state of disaster readiness. Thirty agencies returned completed questionnaires. Of these, 90% have written disaster plans, but only 33% conduct regular drills to practice their written plans. A 24-h telephone number is available to patients at 96% of the agencies. One-fourth of the agencies serving ventilator-dependent patients do not make utility companies aware of their special needs. Of 11 hospital-sponsored agencies, 18% include backup agreements with other agencies, while 79% of non-hospital-sponsored agencies have planned such backup. The majority (92%) of "private-for-profit" agencies have backup arrangements, but only 38% of the public or nonprofit agencies have such arrangements. Additionally, 31% of the home health care agencies do not feel they would be able to meet the needs of their clients in the event of a disaster. Specific recommendations for such agencies in developing disaster plans, and exercising them, are made. PMID- 7884202 TI - Human T-cell lymphotrophic virus type-I (HTLV-I) retrovirus and human disease. AB - Human T-cell lymphotrophic virus type-I (HTLV-I) was the first pathogenic retrovirus identified in humans. HTLV-I is now linked to a number of clinical diseases, most notably adult T-cell leukemia/lymphoma and the syndrome known as HTLV-associated myelopathy or tropical spastic paraparesis (HAM/TSP). For the emergency physician practicing among patients from high-risk groups, HTLV-I infection and its associated diseases are presenting an increasing challenge. This report describes its transmission, seroprevalence, associated diseases, and methods to control the spread of this retrovirus. PMID- 7884203 TI - Octave Landry: Guillain-Barre syndrome. AB - The clinical features of Guillain-Barre syndrome were initially described by Octave Landry in 1859. Subsequently, Guillain, Barre, and Strohl described a similar syndrome that also displayed a marked increase in cerebrospinal fluid albumin without an increase in white blood cells--an "albuminocytologic dissociation." The hallmark clinical findings in Guillain-Barre syndrome are symmetrical ascending paralysis and areflexia. The differential diagnosis is large, and early cases are often misdiagnosed. Of importance to the emergency physician are the various spinal cord compression syndromes that may present in similar fashion. Acute therapy includes hospitalization and frequent assessment of vital capacity to determine the need for ventilatory assistance. PMID- 7884204 TI - The complex legacy of the sage of Monticello. PMID- 7884205 TI - Gabrielle takes off. PMID- 7884206 TI - Equipment organization in the emergency department adult resuscitation area. AB - It is important to design the resuscitation area in the emergency department to avoid restrictions to movement of personnel around the patient and to enable rapid and efficient access to equipment. The delivery of monitors and gases from above will reduce interference to flow by mechanical components. Preassembled airway equipment and the organization of equipment using an intuitive system, such as anatomic arrangement, aids in the rapid location of needed equipment. PMID- 7884207 TI - Relief of posttraumatic headache by intravenous chlorpromazine. AB - We report the case of an 18-year-old male with a vascular-type headache occurring 3 days after a minor closed-head injury. The headache resolved completely, without recurrence, with a single dose of intravenous chlorpromazine. This case and the few others reported in the literature illustrate that the response of a headache to antimigraine therapy cannot be relied upon to diagnose or confirm a diagnosis of migraine headache, or to rule out other intracranial pathology. PMID- 7884208 TI - Emergency pain management: a Canadian Association of Emergency Physicians (CAEP) consensus document. AB - Pain is the most common presenting complaint heard in Emergency Medicine, yet it is poorly controlled. Evaluation of this pain should be with use of objective pain scales completed by the patient, not relying on physician impression. Treatment modalities available in the Emergency Department, a review of medications and their dosing as well as specifics to pediatric pain management are presented. The final section reviews situation or diagnosis specific pain control: headaches, renal colic, polytrauma victims, abdominal pain, soft tissue injury and acute arthritis. These recommendations are based on a Canadian Association of Emergency Physicians (CAEP) consensus conference held in April 1993. The literature was reviewed extensively and used as the basis for the consensus workshops and discussion. At the writing of the consensus paper, however, no specific ideas were borrowed from any one article. The appended bibliography is suggested reading, selected from the larger literature review. There are to date few controlled multi centre trials in overall pain management that would allow guidelines to be produced. PMID- 7884209 TI - Platelet occlusion phenomenon after short- and long-term survival following complete cerebral ischemia in rats produced by cardiac arrest. AB - Platelet interaction with cerebral microvessels was studied in rats after global brain ischemia. Studies were performed with a model of global central nervous system ischemia produced by cardiocirculatory arrest in normothermic rats. The ischemic period of 5-min was followed by times of recirculation lasting 5 and 15 mins, 1, 3, 6, 24, and 48 hrs, and 6, 10, and 12 months. After different periods of survival, blood vessels from brains were examined by transmission electron microscopy. Our investigation revealed numerous platelet aggregates of varying sizes within both arterial and venous intraparenchymal vessels. At the same time, we also noted platelets in various stages of disintegration. Platelets close to the endothelial cells were often degranulated, with shape changes including pseudopodia. Aggregates of platelets were focal, random, and more widespread occurring in the cerebral cortex, thalamus, basal ganglia, hippocampus, and cerebellum. We also observed recent aggregates of platelets and thrombi, which presented varying degrees of degranulation. In one time period, some platelets were found outside the brain vessels (in the perivascular space after 24 hrs of survival). We present evidence that platelet aggregation was repeated a long time after the ischemic incident, i.e., after one year. The main result was a prominent and local accumulation of platelets in microvessel branches or regions of vessel bifurcations, which correlated well with blood-brain barrier alterations observed previously in this model. The platelet aggregations increased in frequency with longer periods of recirculation. We noted that local platelet adhesion/aggregation was present after brain ischemia requiring no denudation or exposure of the basal lamina.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884210 TI - Distribution of calbindin D28k immunoreactive cells and fibers in the monkey hippocampus, subicular complex and entorhinal cortex. A light and electron microscopic study. AB - Calbindin D28k (CB)-containing neurons and axon terminals in the hippocampus, subicular complex and entorhinal cortex of the African green monkey (Cercopithecus aethiops) were studied by light and electron microscopic immunocytochemistry. CB was present in granule cells of the dentate gyrus, pyramidal neurons of hippocampal fields CA1 and CA2, and in pyramidal neurons of the prosubiculum and entorhinal cortex. In contrast, pyramidal neurons in the CA3, subiculum and presubiculum were not labeled. A subpopulation of non principal neurons (non-granule and non-pyramidal cells) was also stained for CB. These cells were rare in the hippocampus and subiculum, but were more frequently observed in the presubiculum, parasubiculum, and in the entorhinal cortex. In the electron microscope, these non-principal cells displayed fine-structural characteristics of GABAergig neurons. Strongly stained CB-immunoreactive bundles of myelinated axons were found in the molecular layer of the subiculum and in various layers of the presubiculum. The CB-positive, unmyelinated axons of the granule cells, the mossy fibers, gave rise to distinct fiber bundles. Mossy fiber terminals formed asymmetric synapses on large spines in the hilus and CA3. In addition to the giant mossy fiber boutons, there were large CB-positive terminals that formed asymmetric synapses with dentritic spines throughout the hippocampal formation. These boutons also formed axo-dendritic synapses in the entorhinal cortex. Axon terminals that formed symmetric synapses and might, thus, be derived from non-principal neurons, were rarely found in the hippocampus and subicular complex. They were more frequent in the parasubiculum and entorhinal cortex. These CB-positive terminals were small, heavily immunostained, and formed symmetric axo-dendritic synapses. Our results demonstrate a great diversity of CB containing neurons, axons, and terminals in the monkey hippocampal formation. In general, regions that received a dense innervation of CB-positive terminals displayed pyramidal neurons that all lacked this calcium-binding protein. Further studies are required to understand the functional significance of these findings. PMID- 7884211 TI - Localization of insulin-like immunoreactive neurons in the hypothalamic paraventricular and supraoptic nuclei of streptozotocin-induced diabetic rats. AB - Insulin-like immunoreactive (ILIR) neurons were localized in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON) of normal as well as streptozotocin-induced diabetic rats at different time intervals ranging from 1 to 12 months post-diabetes. Insulin-like immunoreactivity was localized in the cytoplasm and nucleoplasm of the neuronal somata in the PVN and SON of control rats but the nucleolus appeared unlabelled. In the neuropil of PVN and SON, the reaction product was mainly localized in the dendrites and axonal profiles. The overall intensity of labelling was light and diffuse. In streptozotocin-induced diabetic rats, also the PVN and SON contained ILIR neuronal somata, dendrites and axonal profiles. However, these ILIR neuronal profiles displayed abnormality at all the time intervals studied. At 1-6 months post-diabetes, the ILIR somata and dendrites appeared to be hypertrophied and they contained dilated endoplasmic reticulum. Both ILIR myelinated as well as non-myelinated axons were also present in the neuropil. Numerous unlabelled axon terminals showing swollen agranular as well as dense-cored spherical vesicles were also present in the neuropil and they were presynaptic to labelled dendrites. At 9-12 months post-diabetes, some of the ILIR neuronal profiles appeared to be degenerating. The ILIR somata showed distended rER, membranous bodies and autophagic vacuoles. Highly vacuolated ILIR dendritic processes were also present in the neuropil. It is hypothesized that streptozotocin-induced diabetes produced a state of hypoinsulinemia or hyperglycemia which in turn sensitized the PVN and SON resulting in hyperactivity of the ILIR neurons and the prolonged stimulus could have possibly produced the neuronal degeneration seen at later survival periods. PMID- 7884212 TI - Cytochemical and immunocytochemical comparative localization and characterization of acid sulfated glycolaminoglycans (sGAG) in several areas of the rat cerebral cortex during postnatal development. AB - There are some evidences demonstrating that Acid Sulfated Proteoglycans take part in several Central Nervous System (CNS) functions (Brittis et al., 1992; Carbonetto, 1989; Carey et al., 1990, 1992; Fichard et al., 1991; Kalb and Hockfield, 1990; Lafont et al., 1992; Schubert and Lacorbiere, 1985; Schubert et al., 1988, 1989; Snow et al., 1990, 1991, 1992). To date, the immunocytochemical methods have been developed to detect different proteglycans using specific monoclonal antibodies (Bertolotto et al., 1991; Watanabe et al., 1989; Zaremba et al., 1989). The aim of the present paper is to compare the localization of chondroitin-0-sulfate, -4-sulfate, -6-sulfate and keratan sulfate proteglycans in the rat cerebral cortex during the postnatal development, using both colloidal iron and immunocytochemical methods. Our observations, with the light microscope, revealed an intense immunocytochemical reaction closely associated to the neuronal membranes that, in most cases, were located in the III, IV, V and VI cortical layers of the 20 and 30 postnatal day rats, but not in the 7 and 15 postnatal ones. The colloidal iron reaction revealed similar distribution as that one observed with the immunocytochemical method for chondroitin-0-sulfate, -4 sulfate, -6-sulfate proteoglycans. At electron microscopic level it has been observed positive immunostaining for these sulfated proteoglycans on the plasma membrane of these scattered neurons. Positive immunoreaction for Keratan sulfate proteoglycan was demonstrated inside several astrocytes of 7, 15, 20 and 30 postnatal day rat cerebral cortexes, but it has not been observed in neurons. Taking into account the previous biochemical studies, our observation have led us to suggest that a unique membranous protein could be binded to several acid sulfated glycosaminoglycans (sGAG) types in a particular neuronal subset. PMID- 7884213 TI - Morphometric study on the postnatal growth of the cerebral cortex of Australian aborigines and Caucasians. PMID- 7884214 TI - Morphometric study on the postnatal growth of the visual cortex of Australian aborigines and Caucasians. PMID- 7884215 TI - Decrease of gap junction number in the rat neural tube between ED 11 and ED 15. AB - The apical regions of neuroepithelial cells of 11 and 15 day-old rat embryos were found to be interconnected near their luminal surface by extended junctional complexes, consisting of tight junctions and desmosome-like contacts. On the 11th and 12th embryonal day, small gap junction cell contacts occur in the juxtaluminal region of the neural tube. Besides these intercellular gap junctions, annulated gap junctions, located intracellularly, were also detected at this developmental stage. The latter type is thought to originate from intercellular gap junctions by an invagination process in the course of degradation of extended contacts which exist between neuroepithelial cells in earlier developmental phases. The decrease of gap junction number by the 14th and 15th embryonal day could be correlated with processes of cellular development and differentiation. PMID- 7884216 TI - Visceral leishmaniasis: more prevalent and more problematic. PMID- 7884217 TI - Outcome of Toxoplasma gondii mismatches in heart transplant recipients over a period of 8 years. AB - Donor-related infection due to Toxoplasma gondii is a well-recorded complication of cardiac transplantation. In order to assess the efficacy of co-trimoxazole in small doses as prophylaxis for primary Toxoplasma gondii infection in seronegative heart and heart-lung transplant recipients receiving organs from seropositive donors, we reviewed the serostatus and clinical outcome of all such mismatched transplants performed at our unit over a period of 8 years. Of 310 transplants performed between May 1985 and May 1993, donor and recipient serum samples were available for 257 heart and 33 heart-lung transplants. Of these, 13 (4.5%) were toxoplasma mismatches. Post-transplant review serum samples were available for 3 months or longer for nine of the 13 mismatches. The first three patients received co-trimoxazole 480 mg bd orally for 3 months (regimen A) while the remainder received only the standard prophylaxis designed for Pneumocystis carinii i.e., 960 mg bd orally three times per week for 3 months (regimen B). Seroconversion was demonstrated in only one patient (regimen A). Furthermore, none of the mismatched patients developed serious infection compatible with primary toxoplasmosis. We therefore conclude that in centres with a low prevalence of toxoplasma seropositivity, testing of donor and recipient serum for Toxoplasma gondii antibody should be performed only when clinically indicated and, in addition, standard prophylaxis for Pneumocystis carinii may be adequate for preventing primary toxoplasmosis. PMID- 7884218 TI - Treatment of late Lyme borreliosis. AB - The aim of this study was to develop a treatment for late Lyme borreliosis and to compare the clinical results with serological findings before and after treatment. It was done in the Aland Islands (population 25,000), a region endemic for Lyme borreliosis. The patients were the first consecutive 100 patients from the Aland Islands with late Lyme borreliosis. They were followed for at least 1 year after treatment. The clinical results of treatment were compared with results of analyses of flagellar IgG antibodies to Borrelia burgdorferi done at the time of diagnosis before treatment and up to 12 months afterwards. Short periods of treatment were not generally effective. The outcome was successful in four of 13 treatments with 14 days of intravenous ceftriaxone alone, in 50 of 56 assessable treatments with ceftriaxone followed by 100 days of amoxycillin plus probenecid, and in 19 of 23 completed treatments with ceftriaxone followed by 100 days of cephadroxil. Titres of IgG antibodies to B. burgdorferi flagella declined significantly after 6 and 12 months in the patients who had successful treatments. All patients whose final titres were less than 30% of the initial titre were in the successful group. Their titres usually remained above the upper limit of normal for a long time but a decline to a value of less than 30% of that before treatment was always a sign of cure. PMID- 7884219 TI - Hepatitis C virus infection in sexually active homosexual men. AB - While hepatitis C virus (HCV) is known to be transmitted parenterally, the role of sexual transmission remains unclear. In order to examine the association of sexual risk factors with HCV seroprevalence at a time when unprotected sexual practices were still quite common, 435 homosexual men recruited from a municipal sexually transmitted disease clinic with behavioural data and serologic specimens from 1983-1984 were evaluated. Overall, 25% of men reporting injecting drug use (IDU) and 5% of men with no IDU were anti-HCV positive; the rate in the non-IDU was significantly higher than age-matched rates in blood donors (summary odds ratio 3.5, 95% confidence interval 2.8-4.2). In addition to IDU, amphetamine and phencyclidine use were also associated with anti-HCV positivity on univariate analysis. Sexual risk factors for anti-HCV positivity included anal receptive intercourse, 'fisting', having an IDU sexual partner, a self-reported history of genital herpes and HIV seropositivity. On multivariate analysis, only IDU was significantly associated with anti-HCV positivity. Thus, sexual practices appear to play a minor role in transmission of HCV. PMID- 7884220 TI - Serum concentrations of soluble intercellular adhesion molecule-1 and progress towards disease in patients infected with HIV. AB - Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule that is primarily involved in cell to cell adhesive interactions of the immune system. Concentrations of soluble ICAM-1 (s-ICAM-1) shed into the circulation were measured by a quantitative ELISA in HIV-infected persons without AIDS, patients with AIDS with or without evidence of acute opportunistic infection at the time of sampling, and HIV-seronegative patients with toxoplasmosis, community-acquired pneumonia, leishmaniasis and rickettsial infections. Patients were classified on the basis of clinical condition and CD4+ T-cell counts according to the 1993 revised HIV classification of the USA Centers for Disease Control. Concentrations of s-ICAM-1 in the serum of HIV-infected persons without AIDS-indicator conditions (categories A1, A2, B1 and B2) as well as in the serum of patients with AIDS (categories A3, B3, C1, C2 and C3) were significantly higher than normal (mean +/- S.E.M. 469 +/- 23, n = 60 and 780 +/- 73, n = 56, respectively, versus 329 +/- 15 ng/ml, P < 0.0001 and < 0.0001 respectively) and differed also significantly from each other (P < 0.0001). Raised concentrations of s-ICAM-1 in the serum of afebrile patients with AIDS but without acute opportunistic infection at the time of sampling (mean +/- S.E.M. 672 +/- 76, n = 29) did not differ from those of the remaining patients with AIDS or from those of HIV seronegative patients with the infections studied. A steady and significant increase of serum concentrations of s-ICAM-1 with progress of disease according to clinical category (categories A-->B-->C, p = 0.0007) as well as with the loss of circulating CD4+ T-cells (categories 1-->2-->3, p = 0.009) was observed. Individual serum concentrations of s-ICAM-1 showed negative correlations with individual total lymphocyte (P = 0.004), CD4+ T-cell (P = 0.05), CD8+ T-cell counts (P = 0.03) as well as positive correlation with serum concentrations of soluble interleukin-2 receptors (P < 0.0001), an indirect marker of progress of HIV-related disease. Serum concentrations of s-ICAM-1 did not differ between patients with AIDS who were receiving or not receiving zidovudine at the time of sampling. A longitudinal survey is needed in order to determine whether measuring serum concentrations of s-ICAM-1, although not specific, has any predictive or prognostic value in these patients as well as whether this bioactive molecule has any pathogenetic role in the progress of disease in HIV infection. PMID- 7884221 TI - Neonatal Haemophilus influenzae infections. AB - Thirteen cases of neonatal Haemophilus influenzae (HI) infections were identified in Al-Baha Region, Saudi Arabia during 1 year: seven male, six female. The mean weight and age were 36.0 weeks (28-44) and 2.5 kg (1.1-4.5) respectively. All babies were delivered outside the hospital, five at home and eight at primary care centres. HI was isolated from the lungs in 12 (92%), eyes in seven (54%), and from the blood in four (31%). None of the neonates had meningitis. HI resistant to ampicillin and cefuroxime were identified in one case (7.7%) each. All survived and were discharged home in good condition. Our findings suggest that HI is becoming more recognised as a cause of neonatal infections especially in premature babies. The current starting regimen of antibiotics for suspected sepsis in neonates (ampicillin and gentamicin) adequately cover for HI sepsis and need not be changed unless lack of response to treatment is documented. PMID- 7884222 TI - Meningococcal meningitis with 'normal' cerebrospinal fluid. AB - A prospective study was made of all patients with normal CSF counts and positive cultures for Neisseria meningitidis diagnosed in "El Valles" County, Barcelona between January 1987 and December 1990. Meningococcal meningitis was documented in 82 patients, eight of whom (seven children, five boys and two girls with a mean age of 5.6 +/- 3.3 years, and a 69-year-old male patient) had no apparent CSF abnormalities in the initial lumbar puncture. At the time of admission all patients had fever (mean 39.1 degrees C) of 10.8 +/- 5.6 hour duration and petechial rash which had been present for a mean of 3.6 +/- 3.3 hours. Signs of meningeal irritation were not found. A 4-month-old infant with symptoms of circulatory collapse, intracranial hypertension and impairment of consciousness subsequently died of septicemia in 48 hours. Group B N. meningitidis was isolated in six cases (reduced penicillin-susceptibility in two cases) and group C N. meningitidis in the remaining two (reduced penicillin-susceptibility in one case). Patients without pleocytosis did not differ in a statistically significant fashion from the patients with high pleocytosis in the duration of temperature, and petechial rash, leukopenia, positive blood culture and fatal outcome. PMID- 7884223 TI - Coagulase-negative staphylococcal bacteraemia with special reference to septic shock: experience in an intensive care unit. AB - During a period of 4.5 years, 48 patients with bacteraemia due to coagulase negative staphylococci were studied prospectively in order to evaluate their clinical profile, management and outcome. There were 25 males and 23 females with ages ranging between 13 and 100 years. Over 60% of patients belonged to the age group 30 to 69 years. Shock was recorded in 23 (48%) of the 48 patients. Of the shocked patients, 16 were immunocompromised and also had abnormal coagulation. Their mortality was 44%. By contrast, none of the immunocompromised patients without shock died. Abnormal coagulation was found in 17 patients without septic shock. Their mortality was 5.9%. The commonest underlying disease was respiratory failure especially in shocked patients. The source of infection was identified in the majority of cases. In addition, most patients had an indwelling intravascular catheter especially an arterial one. The overall mortality was 16.7% (8/48). It was significantly higher in patients with shock than in those without shock (30.4% vs. 4.0%, P < 0.05). PMID- 7884224 TI - Biotyping of Campylobacter jejuni and Campylobacter coli infections in Spain. AB - Biochemical profiles were studied in 102 Campylobacter isolates from patients affected by enteric disease in Orense (Spain) over a 1-year period. The isolates were identified as hippurate-positive Campylobacter jejuni (n = 90), Campylobacter coli (n = 10) and hippurate-negative C. jejuni (n = 2). Seventy seven of the hippurate-positive and both hippurate-negative C. jejuni isolates were biotyped as C. jejuni subsp. jejuni biotype 1, nine as C. jejuni subsp. jejuni biotype 2 and four as C. jejuni subsp. doylei. Hippurate-hydrolysis was correlated to a simple scheme based on L-arginine arylamidase production, propionate assimilation and malate assimilation which yielded sensitivity and specificity values of 0.90 and 1.00, respectively. Effective grouping of nalidixic acid-resistant C. jejuni and C. coli isolates (38.5% of the total) was also achieved. PMID- 7884225 TI - Barnett Christie Lecture (1993). The natural history of HIV infection: a study in Edinburgh drug users. PMID- 7884226 TI - Mycoplasma fermentans and HIV-associated nephropathy. AB - We describe a patient in whom HIV-associated nephropathy developed in association with the detection of Mycoplasma fermentans. This mycoplasma was found in renal tissue by means of a polymerase chain reaction when nephropathy was first evident, and subsequently in urine, blood and the throat. The evidence presented strengthens the causal association of this micro-organism with HIV-induced nephropathy. PMID- 7884227 TI - Stomatococcus mucilaginosus lower respiratory tract infection in a patient with AIDS. AB - We describe a case of recurrent Stomatococcus mucilaginosus lower respiratory tract infection in a patient with AIDS. Apart from S. mucilaginosus no other pathogens were found to account for infection. There was a rapid response to rifampicin, the organism being resistant to penicillin, co-trimoxazole and ciprofloxacin. Infections caused by this organism are increasingly described, but there are few reports of lower respiratory tract infection. PMID- 7884228 TI - Cytomegalovirus encephalitis in two patients with AIDS receiving ganciclovir for cytomegalovirus retinitis. AB - Cytomegalovirus (CMV) encephalitis has been reported with increasing frequency in patients with AIDS. Nevertheless, the management of CMV-related encephalitis appears to be problematic and data in the literature on the clinical efficacy of ganciclovir therapy is sparse and controversial. We describe two patients with AIDS who developed CMV encephalitis while receiving ganciclovir maintenance therapy for CMV retinitis. Moreover, there was no improvement in neurological status or virological and radiological response during a further induction course of ganciclovir. These observations suggest that the currently recommended therapeutic protocols with ganciclovir are not effective in the prevention and treatment of CMV encephalitis in patients with AIDS. PMID- 7884229 TI - Primary meningococcal pericarditis with cardiac tamponade in an infant. PMID- 7884230 TI - High incidence of haemorrhagic colitis due to Escherichia coli O157 in one Scottish town: clinical and epidemiological features. AB - Verotoxin-producing strains of Escherichia coli (VTEC), in particular serotype O157:H7, are now recognised as the major cause of haemorrhagic colitis and the haemolytic uraemic syndrome (HUS) in the U.K. and in North America, and increasingly so in other countries. Over a 3-year period (1989-1991), 16 cases of E. coli 0157 infection occurred in one town (Peterhead) in north-east Grampian. Four patients required admission to hospital, of whom three developed HUS. The bovine source of VTEC infection has now been clearly established with foodborne, waterborne, person-to-person and zoonotic transmission described. Despite extensive local enquiries, the source(s) of infection of the 16 cases in Peterhead was not established. Much still needs to be learned about the epidemiology, risk factors and long-term clinical sequelae of VTEC infection and HUS. Close collaboration between the medical and veterinary professions is of paramount importance in order to provide better understanding of the prevalence of E. coli O157 infection in cattle and the route(s) of transmission to humans. PMID- 7884231 TI - An account of bubonic plague in seventeenth century India in an autobiography of a Mughal emperor. PMID- 7884232 TI - Intrafamilial transmission of hepatitis C virus. PMID- 7884233 TI - Morganella morganii meningitis in a patient with AIDS. PMID- 7884234 TI - Antinuclear antibodies in visceral leishmaniasis. PMID- 7884235 TI - Kinetoplast-associated proteins as potential drug targets and diagnostic markers for trypanosomiasis. PMID- 7884236 TI - Clinical outcome of intraoperative pelvic hyperthermochemotherapy for patients with Dukes' C rectal cancer. AB - In attempts to prevent local recurrence after curative resection for rectal cancer, intraoperative pelvic hyperthermochemotherapy (IOPHC) was prescribed for 27 patients with Dukes' C cancer. The procedures used were as follows: immediately after amputation or resection of the rectum with extended lymphadenectomy, the pelvic cavity was filled with physiological saline containing 40 micrograms/ml mitomycin C, which was warmed at 45 degrees C for 90 min with an apparatus devised for IOPHC. Thirty-five patients who underwent surgery alone for Dukes' C rectal cancer within the same period served as controls. There was a local recurrence in three patients in the IOPHC group (11.1%), and in 13 in the control group (37.1%). With regard to hepatic or pulmonary metastasis, there was no difference between the two groups. There was no morbidity in the IOPHC treatment except for a large volume of exudate from the pelvic cavity. Thus, IOPHC can be considered as one option for limiting local recurrence after surgical resection of an advanced rectal cancer. PMID- 7884238 TI - Dose uniformity in scanned focused ultrasound hyperthermia. AB - Scanned focused ultrasound (SFUS) is unique amongst noninvasive methods of inducing hyperthermia in that the absorbed power (SAR) distribution may be controlled at a scale of 0.5 cm or better. This high degree of spatial control of SAR implies that differences in local tissue cooling due to heterogeneity in perfusion, variations in the density of discrete thermally significant vessels and even local cooling around single large vessels may be compensated during SFUS treatments. In this paper we calculate thermal dose distributions arising from three different SFUS techniques: (1) the high-temperature short-duration (HTSD) ultrasound technique; (2) conventional systems employing a fixed scan and fixed SAR simulated by a uniform SAR; and (3) we optimize the SAR distribution using information from angiography and thermal models. These techniques are tested in the same anatomy having discrete vessels, a non-uniform vessel density and with little, if any, preheating of the incoming blood (i.e. the worst-case situation). The application of a uniform SAR to this volume resulted in a highly non-uniform thermal dose distribution. The situation is clearly improved in HTSD hyperthermia; however, the desired accuracy of positioning within the tumour is high, and to minimize background heating the focus must be stepped slowly and preferably in a semi-random pattern through the target volume. The third technique which employs spatial control over SAR resulted in the greatest uniformity in thermal dose. However, the use of this technique requires the input of the complete three-dimensional discrete vessel network and the availability of a tested three-dimensional discrete vessel thermal model. PMID- 7884237 TI - Finite element simulation of Sigma 60 heating in the Utah phantom: computed and measured data compared. AB - An initial series of comparisons are made between finite element computations and laboratory measurements obtained during heterogeneous phantom heating with the Sigma 60 applicator. The phantom is a relatively complex, though still idealized, rendering of the pelvic area which has been used to study the deep heating characteristics of the Sigma 60 in this anatomy. Direct electric field measurements as well as inferred SAR through transient temperature analysis are plotted against computed results along 11 one-dimensional tracks through the phantom. Quantitative comparisons provided through the track-by-track analysis show generally good agreement between computation and measurement. The finite element method is found to predict well the jumps in the electric field when polarized perpendicularly to a muscle/fat interface. Visualizations of the complete three-dimensional distributions are also highlighted and correlate well with physical reasoning about the expected behaviour of the fields produced. Some discrepancies in the data persist and are discussed and analysed in depth. They underscore the difficulties that can arise in performing comparisons between measured and computed results and stress the need for careful and thorough investigations when attempting these types of model validation studies. PMID- 7884239 TI - Hyperthermic potentiation of cisplatin toxicity in a human small cell lung carcinoma cell line and a cisplatin resistant subline. AB - A human small cell lung carcinoma cell line (GLC4) and its subline with in vitro acquired cisplatin (cDDP) resistance (GLC4-cDDP) were used to study the applicability of hyperthermia to interfere with acquired cDDP resistance. GLC4 and GLC4-cDDP did not differ in heat sensitivity (clonogenic ability). Both cell lines could be sensitized to cisplatin to a considerable extent, both at 42 and 43 degrees C. For 42 degrees C hyperthermia treatments up to 90 min no differences in TER between the cell lines were observed. Only prolonged (> or = 45 min) exposures to 43 degrees C hyperthermia sensitized the resistant cell line to a greater extent than the parent cell line, resulting in a reduction of the resistance factor from 3.6 (at 37 degrees C) to 1.7 (60 min 43 degrees C). The finding in this human system that for treatments up to 90 min, 43 degrees C heat is more suitable than 42 degrees C heat to reduce cDDP resistance, is in accordance with earlier findings with murine cells (Konings et al. 1993). Effects of heat, cisplatin and combined treatments on cell killing were not only measured with the clonogenic assay, but also with the microculture tetrazolium method (MTT assay), an assay of potential use in the clinic for rapid screening of cells obtained from patients. The data with the latter assay were comparable to those obtained with the clonogenic assay. However, its applicability to measure thermo chemosensitization is limited due to its inability to measure more than one log of cell killing. PMID- 7884240 TI - Effect of whole body hyperthermia on carboplatin disposition and toxicity in dogs. AB - Fifty dogs with refractory or disseminated spontaneous tumours were evaluated in two independent phase I studies using either carboplatin (CBDCA) alone or CBDCA plus whole body hyperthermia (WBH). CBDCA was administered as a 30 min infusion at the onset of the plateau phase of WBH in dogs receiving combined treatment. Serum samples were collected and drug disposition was determined in both treatment groups. The dose-effect relationship was mathematically described with a logistic regression model developed from categorical toxicity data accumulated throughout the first two treatment courses in all dogs. The maximum tolerated dose (MTD) was defined as that dose which resulted in a 50% probability of achieving moderate or severe toxicity. The only toxicities observed were neutropenia and thrombocytopenia, which were dose-dependent. The nadir occurred between 7 and 14 days following treatment. A significant decrease in the area under the serum CBDCA versus time curve for dogs undergoing WBH was consistent with increased tissue binding of the drug as well as increased urinary eliminations. Serum AUC values determined following the first course of treatment were predictive of subsequent toxicity in both treatment groups. The MTD (95%CI) for CBDCA and CBDCA/WBH were estimated to be 318(44) and 239(51) mg/M2 respectively (p = 0.08). A randomized phase II evaluation should be initiated to determine if a therapeutic gain can be achieved using combined CBDCA and WBH. Further refinement of the CBDCA dose in such a trial should be based on both pharmacokinetic parameters and normal tissue response. PMID- 7884241 TI - Interaction between adriamycin cytotoxicity and hyperthermia: growth-phase dependent thermal sensitization. AB - Thermal sensitization of adriamycin cytotoxicity was studied in vitro and in vivo using tumour cells originated from a spontaneous mouse fibrosarcoma, FSa-II. The adriamycin dose-cell survival curve for exponentially growing cells was biphasic with the initial sensitive portion followed by a resistant tail. The survival curves determined in vitro as a function of treatment time at various temperatures were also biphasic. With increasing temperatures the initial portion became steeper and the resistant fraction decreased. At a temperature of 43 degrees C, which gives lethal damage to cells by itself, the cell survival decreased rapidly during the initial 30 min of treatment and became relatively constant for subsequent treatment times up to 180 min. The tumour response determined by the median tumour growth time for one-half of treated tumours to reach 1000 mm3 from the treatment day (35 mm3) indicated that the tumour response to adriamycin was independent of temperature. Hyperthermia at 43.5 degrees C for 60 min prolonged the tumour growth time without showing chemosensitization. The maximum drug dose used was 12 mg/kg that is < LD10 or the drug dose that kills animals with < 10% probability. The dose-response curves (tumour growth versus drug dose) showed identical slopes at room temperature, 41.5 and 43.5 degrees C. Further studies were conducted in vitro. Plateau phase cells were treated with graded adriamycin doses for 60 min at 37 degrees C, or with a constant adriamycin dose of 0.25 microgram/ml for various times at 37 or 43 degrees C. The dose-cell survival curves for both exponential and plateau phase cells were biphasic, but the plateau phase cells were more resistant to adriamycin at 37 degrees C than the exponential phase cells. The survival curve for plateau phase cells, determined as a function of treatment time, showed an initial shoulder followed by an exponential portion. Compared with the heat survival curve at 43 degrees C, the survival curve for the drug treatment at 43 degrees C was identical to that for the heat alone treatment for the first 60 min and then became steeper than the heat alone survival curve. These results suggest that adriamycin cytotoxicity may be enhanced at elevated temperatures only when tumours are treated for a prolonged time or possibly with a large drug dose. PMID- 7884242 TI - Effect of protracted mild hyperthermia on polymerase activity in a human melanoma cell line. AB - Radioresistant human melanoma SkMel-3 was evaluated with its sensitivity to thermal cell killing and polymerase inactivation. Cells were heated from 40 to 45 degrees C and demonstrated no thermal tolerance development for any of the temperatures tested. In addition, at 45 degrees C the heat survival curve showed a large shoulder indicating capacity for accumulation of sublethal heat damage. Also at 45 degrees C heating polymerase beta was more sensitive than polymerase alpha + delta + epsilon. At 42 degrees C, the polymerase sensitivities were nearly the same but at the lower temperatures (41 and 40 degrees C) polymerase beta became progressively more resistant than the polymerase alpha + delta + epsilon. Thus, mild hyperthermia effects may be different than high temperature hyperthermia and may be related to polymerase alpha + delta + epsilon activity. PMID- 7884243 TI - Interstitial hyperthermia and interstitial radiotherapy of a rat rhabdomyosarcoma; effects of sequential treatment and consequences for clonogenic repopulation. AB - Animal tumour experiments have been performed to elucidate the interactions between interstitial hyperthermia (IHT) and interstitial radiotherapy (IRT), and to obtain information about the most effective sequence of these treatment modalities. Experimental tumours, transplanted in the flank of Wag/Rij rats, were treated with IHT for 0.5 h at 44 degrees C, and with IRT using low dose-rate (LDR) iridium-192 sources. Both tumour cure probability and the fraction of clonogenic cells in vitro after different IHT and IRT treatments in vivo, were used as endpoints. The sequence of a short (0.5 h) IHT treatment followed by an extended LDR-IRT treatment lasting up to 10 days appeared to be very effective, and resulted in a significant thermal enhancement ratio of 1.34 at the 50% tumour cure probability level. A not significantly increased thermal enhancement of 1.06 was found when the same IHT treatment followed IRT. The level of clonogenic cell survival after IHT alone is high (0.24 +/- 0.08) compared with that after an IRT dose of 20 Gy (0.017 +/- 0.004). Clonogenic cell repopulation started 2-4 days after the in vivo treatment irrespective of the type of treatment. The in vivo combination of IHT and LDR-IRT resulted in lower surviving fractions compared with IRT alone, regardless of the time interval between the end of treatment and in vitro clonogenic assay. IHT followed by LDR-IRT appeared to be the most effective treatment in terms of tumour cure. The in vivo/in vitro studies indicated that the effect of hyperthermia is mainly attributed to radiosensitization, possibly by partial inhibition of sublethal damage repair processes during the subsequent irradiation. The hyperthermia-induced cytotoxicity was of minor importance as estimated from the surviving clonogenic fraction. PMID- 7884245 TI - [Surgical repair of post-infarction ventricular septal defects--reconstruction with pericardial patch]. AB - Despite improvements in the pre- and postoperative management of patients with post-infarction ventricular septal defects, the results after surgery have been variable. This is in part due to advanced patient age, multi-vessel coronary disease. In addition, resection of the infarcted ventricular septum results in significant compromise in left ventricular function. Since January of 1993, we have used a new technique for the reconstruction of the left ventricle using a single pericardial patch. In this method, which was introduced by Komeda and David in 1990, a single patch is sutured to the interventricular septum and the lateral ventricular wall, excluding the infarcted muscle from the left ventricular cavity. This method was used in the treatment of four patients. There was no bleeding along the suture lines at operation, all of the patients survived. Postoperatively, all four were functional New York Heart Association Class 1. One patient underwent re-operation on the 12th day using the same technique because of a residual shunt. Another two patients had small residual shunts, which spontaneously resolved in 2 to 7 months. Left ventricular function evaluated 1 month after the operation utilizing cardiac catheterization revealed a mean stroke volume index of 40 (range: 32-45 ml/m2, and a mean left ventricular ejection fraction of 71 (range: 70-73%). An excellent functional outcome has thus been achieved with the reconstruction of post-infarction ventricular septal defects using a single pericardial patch. PMID- 7884244 TI - Effects of intraoperative hyperthermia on canine sciatic nerve: histopathologic and morphometric studies. AB - Failure to achieve local control in the treatment of pelvic and retroperitoneal tumours results in a high rate of recurrences. The objective of intraoperative hyperthermia (IOHT) is to enhance the effect of intraoperative radiation therapy and to increase local tumour control. The tolerance of peripheral nerves to heat may limit the heat dose that can be applied to tumours. Histopathologic and histomorphometric changes of canine sciatic nerve after 60-min IOHT were studied in three groups of five dogs each for temperatures of 43, 44 and 45 degrees C. IOHT was performed using a water-circulating hyperthermia device with a multichannel thermometry system on surgically exposed sciatic nerve. Histopathologic and histomorphometric studies were done immediately, 3 weeks and 12 months after IOHT. Histologic changes observed immediately after treatment were minimal but at 3 weeks following 60-min 45 degrees C IOHT both axon and myelin loss and an increase in endoneurial fibrous tissue were observed. Twelve months after treatment a statistically significant decrease in axon, myelin and small vessel percentages as well as an increase in endoneurial and epineural connective tissue were observed for dog treated to 45 degrees C. Dog treated to 44 degrees C for 60 min had similar statistically significant but less severe changes. Twelve months after 43 degrees C IOHT for 60 min, nerve fibres appeared normal and endoneurial connective tissue was only increased mildly around small and medium-sized vessels. These results suggest that temperatures to the peripheral nerve > 44 degrees C for 60 min are likely to cause significant histopathologic changes that can be found 12 months after treatment. A hypothesis of the mechanism of heat injury to peripheral nerves was developed. PMID- 7884246 TI - [Clinical study of two-area coronary bypass by one arterial graft]. AB - In coronary artery bypass grafting (CABG), the possibility of scant flow of arterial graft compared with vein graft is pointed out. This study was carried out to clarify the propriety of two-area bypass by one arterial graft. CABG only with arterial graft was performed on 139 patients from 1992 to 1994, and two-area bypass by one arterial graft was carried in 34 cases (68 branches). The rate of improvement (%) was defined as follows: (number that showed improvement of regional left ventricular (LV) wall motion on post-operative LV graphy/number that showed decreased regional LV wall motion on pre-operative LV graphy) x 100. Sixty six branches were patent, and we evaluated these 66 LV regional wall motions. The rate of improvement in ischemic area was 53.8% (7/13 branches), and 38.1% (8/21 branches) in infarction areas. Compared with the control group, no significant difference was noted. These 34 cases showed no significant differences in mortality, postoperative IABP using rate, incidences of mediastinitis and pleural effusion compared with the control group. In view of good effect for LV wall motion and high safety operative results, this operation is regarded as a useful procedure for expanding indication of CABG only by arterial graft. PMID- 7884247 TI - [Two cases of traumatic aneurysm of the aortic isthmus]. AB - Two cases with blunt traumatic aneurysm of the aortic isthmus were treated recently. One was operated in early stage using heparin-bounded transient aorto aorta bypass. The other underwent delayed operation with aorto-aorta bypass using centrifugal pump. Patch closures with Dacron fabric sealed by equine pericardium were performed in both of them with satisfactory results. We discussed the controversial problems, the timing of the operation and the method of adjunct circulation. PMID- 7884248 TI - [A case of primary mediastinal teratocarcinoma in a young girl]. AB - Primary malignant germ cell tumors of the mediastinum are rare neoplasm, almost always occurring in young adult males. This report described embryonal carcinoma in a 13-year-old girl. The patient was checked up at chest X-ray examination of middle-school pupils on June 1989, and was referred to us because of rapid enlargement of the shadow on October 1989. Chest rentogenograms on admission showed a large mass at the anterior mediastinum, and MRI also revealed a multicystic one extending to the right hemithorax and pressing the superior vena cava and the right atrium. Her serum AFP level was high at 211.1 ng/ml. At operation, on November 6, 1989, a large tumor (110 x 95 x 75 mm) was removed completely through median sternotomy. Histological study of the lesion revealed a wide spread of cystic mature teratoma containing some foci of embryonal carcinoma. Positive immunochemical reaction indicated the presence of AFP in these carcinoma cells. She was treated with 13 courses of anti-cancer chemotherapy by various combinations of CDDP, THP-ADR, VP-16, VCR, ACD, CPM, CBDCA, for one postoperative year. She showed clinical improvement and has continued to be free from recurrence now at 52 months after surgery. PMID- 7884249 TI - [Postoperative choreoathetosis in a case of tetralogy of Fallot]. AB - We presented a case of severe postoperative choreoathetosis which occurred in a 3 year-old boy with tetralogy of Fallot early postoperatively but almost completely recovered within two years after the operation. Because of the large coronary arterial branch on the right ventricular outflow, a small outflow incision and deep hypothermia (lowest rectal temperature was 13 degrees C) and short duration of circulatory arrest (8 minutes) were adopted. Postoperative course was uneventful till the onset of choreoathetosis on the fifth postoperative day. His symptoms and signs of choreoathetosis, oral-facial dyskinesias, hypotonia, affective changes and also pseudobulbar signs were becoming serious during the first week from the onset, but afterwards his condition started getting better gradually every week, and every month. Now, 20 months after the operation, he is almost completely recovered except for small and slow involuntary movements. Though investiations including CT, MRI and EEG were all almost normal, regional nonspecific low area of the frontal lobe and cerebellum was detected by SPECT (single photon emission computed tomography) on the 32nd and 94th postoperative days, respectively. PMID- 7884250 TI - [Esophageal perforation by alkalis--a case report with conservative therapy]. AB - In May 1993, a 59-year-old woman attempting suicide with toilet detergent (1% sodium hydroxide) was hospitalized as an emergency case. She developed sudden high fever (38-39 degrees C) on the 26th admission day. Thereafter diagnosis of left pyothorax due to perforation on caustic esophageal ulcer was made. Subsequent to thoracentesis continuous dranage of the left thoracic cavity ceased the fever after three days. Oral intake began on the 28th and extubation of the dranage was done on the 42nd after admission. Following hospital course of the patient was uneventful and the patient was discharged on the 111th day after admission. Esophagofluoroscopy taken at 6 months after discharge revealed no esophageal stenosis, and the patient returned to full social activities in good health. PMID- 7884251 TI - [Pulsatile total cavopulmonary shunt for hypoplastic right heart syndrome with abnormal systemic venous return--a case report]. AB - A pulsatile total cavopulmonary shunt was successfully performed on a 5-year-old girl with hypoplastic right heart syndrome associated with abnormal systemic venous return; at the same time, modified mitral valve replacement was performed for mitral regurgitation. The right atrium, tricuspid valve and right ventricle were all extremely dimunitive. The diameter of the tricuspid valve was 50% of normal and the volume of the right ventricle was 8.6% of normal. In addition, there were severe subpumonary stenosis, a restrictive ventricular septal defect (VSD) and an atrial septal defect (ASD). The bilateral superior venae cavae (SVCs) and the hepatic vein drained to the left atrium, and the inferior vena cava was infrahepatically interrupted with a hemiazygos connection to the left superior vena cava. At the operation, each SVC was anastomosed end-to-side to each branch of the pulmonary artery (PA). The restrictive ventricular septal defect and stenotic subpulmonary lesion were left. The diameter of the ASD was reduced from 12 mm to 7 mm. The main PA was neither divided nor banded. The pulsatile blood flow from the left heart to the PA was regurated by a native restrictive VSD and stenotic subpulmonary lesion, and that from the right heart via the ASD was limited by reducing the size of the ASD. These described anatomic arrangements produced adequate antegrade pulsatile flow in the PA, which might prevent the development of pulmonary arteriovenous fistulae and, besides permit transfer of drainage of the hepatic vein from the left to the right atrium via the ASD in future. PMID- 7884252 TI - [Aortic root replacement in twin Marfan patients]. AB - We have performed aortic root replacement in twin Marfan patients. They were male and aged 33 years at the times of the operations. One had pneumonia but the other had no complaints. Echocardiography showed geometries typical of annuloaortic ectasia (aortic diameters of 6.4 and 6.8 cm) and a moderate degree of aortic insufficiency. Aortic roots were replaced utilizing composite valve graft and the coronary orifices were reimplanted with Carrel's patch technique. The operations were carried out at almost the same time. The patients had a satisfactory postoperative course. Because of the potential for late dissection or aneurysm in other areas of the aorta, they should have regular follow-up examinations by MRI and CT indefinitely. PMID- 7884253 TI - [Modified David's operation for aortic regurgitation associated with annulo aortic ectasia]. AB - Composite graft replacement of the ascending aorta and aortic valve has been indicated for aortic regurgitation (AR) associated with annulo aortic ectasia (AAE). 29-year-old female with AR due to AAE associated with Marfan's syndrome underwent the replacement of ascending aorta by sparing an aortic valve with good result. Under cardiopulmonary bypass, the proximal ascending aorta was dissected circumferentially down to the ventriculo-aortic junction. The aneurysmal aorta and the all three sinuses of valsalva were excised, leaving 7 mm of arterial wall attached to the aortic valve and small buttons of arterial wall around the both left and right coronary arteries. The aortic valve was reimplanted inside a 28 mm Dacron graft which was calculated by aortic valve leaflet height. The left coronary artery was reimplanted to the graft by interposing a short 10 mm Dacron graft between coronary ostia and graft and the right coronary artery was anastomosed directly to the graft (Piehler's procedure). We called these procedure "modified David's operation". The patient has survived the operative procedure without any complications. Postoperative aortogram showed a competent aortic valve and the peak systolic pressure gradient across the aortic valve was 20 mmHg. We believe this new procedure preserving the native aortic valve is useful for preventing from some complications associated with artificial heart valves. PMID- 7884254 TI - [Thymoma associated with progressive systemic sclerosis--a case report]. AB - A 59-year-old man was admitted to hospital with sclerodactyly and high grade fever. He complained of wrist joint pain and swelling of bilateral hands. Despite of administration of non steroid anti-inflammatory drug and steroid the symptoms were progressive and sclerodactyly spreaded to the forearm. Through the results of the laboratory examination, he was diagnosed as progressive systemic sclerosis (PSS). Chest CT scan showed an anterior mediastinal tumor, and histological examination revealed a spindle cell type thymoma with mild lymphocytic infiltration. During hospitalization, the pulse therapy of steroid was administrated. Progressive sclerodactyly and interstitial pneumonia were improved, but stiffness of hand and joint pain was not diminished. In expectation of improvement of the symptoms, mediastinal tumor was removed. Histological diagnosis was thymoma of epitherial type. After surgery, symptoms decreased and at last diminished, dosage of steroid could be tapered. PMID- 7884255 TI - [Regional work of the left ventricle before and after CABG]. AB - To evaluate the effects of CABG on regional function of the left ventricular wall, regional work of the left ventricular anterior wall was calculated before and after CABG in 8 patients with multivessel coronary artery disease. In all patients, including CABG for LAD branch, complete revascularization was performed. Regional work of the left ventricular wall was calculated as RW (mJ/cm3) = - integral of sigma d epsilon, where sigma = wall stress and epsilon = regional strain (1n (1/H): H = wall thickness). A major and a minor axis, and anterior wall thickness during cardiac cycle were obtained from the left ventriculogram. Preoperatively, the RW varied widely (from -0.9 to 13.3 mJ/cm3). In 4 cases, the RW decreased and in the other cases, it increased. The RW converged in the tight range (from 2.5 to 6.7 mJ/cm3), postoperatively. These results suggest a uniformalization of the RW in the different regions of the left ventricle was established after the complete revascularization. We conclude that the RW obtained from the analyses of sigma-epsilon relationship is a useful index for evaluating the effects of CABG on the treated region of the left ventricle. PMID- 7884256 TI - [Diltiazem abolishes the effect of ryanodine in St. Thomas' Hospital cardioplegic solution on the post-ischemic functional recovery]. AB - Calcium-induced calcium release (CICR) from sarcoplasmic reticulum (SR) may contribute to calcium depletion of SR during the infusion of cardioplegic solution, which may protect the intracellular calcium overload observed during myocardial reperfusion. We have, therefore, investigated (1) the ability of ryanodine-containing cardioplegic solution to enhance myocardial protection and (2) the influence of diltiazem, L-type calcium channel blocker, on the ryanodine enhanced cardioprotective effect in the isolated working rat heart. Hearts (n = 6 8/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer (Ca2+ = 2.4 mM). This was followed by a 3 min infusion of St. Thomas' Hospital cardioplegic solution containing (1) 0 nmol/L of ryanodine or (2) 1.75 nmol/L of ryanodine combined with various concentrations of diltiazem (0, 0.13, 0.25 and 0.50 mumol/L). Hearts were then subjected to 40 min of normothermic (37 degrees C) global ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). (1) The recovery of aortic flow (%AF) was 52.2 +/- 3.5% in the ryanodine-free group. (2) %AF was 72.0 +/- 1.4%, 50.0 +/- 2.6*, 61.7 +/- 3.2* and 58.3 +/- 2.8*% in the 0, 0.13, 0.25 and 0.50 mumol/L diltiazem groups, respectively (*p < 0.05 vs the 0 mumol/L diltiazem group). Creatine kinase (CK) leakage during Langendorff reperfusion was less in the 0 mumol/L diltizaem (plus 1.75 nmol/L ryanodine) group than the ryanodine-free group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884257 TI - [Usefulness of allopurinol for prevention of myocardial reperfusion injury in open heart surgery]. AB - Xanthine oxidase has been demonstrated to be an important factor in postischemic reperfusion injury. Allopurinol is the inhibitor of xanthine oxidase. In this study, we evaluated usefulness of allopurinol for prevention of myocardial reperfusion injury in open heart surgery. Twenty adult patients were divided into two groups; Ap-group (n = 10) were administered allopurinol for seven days just before operation and control-group (n = 10) were administered nothing. The dose of allopurinol was ranged 100-300 mg/day. The dose was determined according to renal function of patients. Coronary sinus blood hypoxanthine, xanthine, uric acid, lactate, pyruvate, CK, and CK-MB levels were measured at before CPB, 5 and 15 min. after aortic declamping, 5 min. after CPB. Hypoxanthine and xanthine levels in Ap-group were significantly higher than those in control-group at 5 and 15 min. after aortic declamping, 5 min. after CPB. Uric acid levels in Ap-group were significantly lower than those in control-group at 5 and 15 min. after aortic declamping, 5 min. after CPB. Lactate, pyruvate, CK, and CK-MB levels were not different between Ap-group and control group. We considered that allopurinol suppressed the reaction rate of xanthine oxidase. Therefore, the levels of intermediates, hypoxanthine and xanthine, were high and, the level of final product, uric acid was low in Ap-group. However, allopurinol had no efficacy for the level of lactate, pyruvate, CK, and CK-MB, in this study. PMID- 7884258 TI - [Valvular surgery for the patients 70 years old or older]. AB - From January 1986 to June 1993, twenty one patients aged 70 years or older with valvular heart disease underwent open heart surgery. There were 12 males and 9 females with a mean age of 71.2 years (range 70 to 76). Eight patients were in NYHA class III, and 4 in class IV preoperatively. AVR was performed in 10 patients, MVR, MVR with TAP, OMC, AVR with MAP, DVR with TAP in 4, 4, 1, 1, and 1, respectively. Mechanical and bioprosthetic valves were replaced in 11, and 9 patients respectively. There were 6 early death (4 operative, 2 hospital). Longer duration of cardiopulmonary bypass (p < 0.05) and aortic crossclamp time (p < 0.05) were the risk factors independently for early mortality. Follow-up of 15 hospital survivors was 100% (8 months-7.7 years, mean: 3.2 years) and cumulative follow-up was 47.6 patients years (PY). There was one late death, and one prosthetic valve endocarditis (2.1%/PY). No other valve-related complications was occurred. Actuarial survival rate and freedom from valve-related morbidity at seven years were 83.3%, and 93.3%, respectively. These results show that operative mortality of valvular disease in elderly patients remains high, but the late results is acceptable one. Valve surgery for these elderly patients is reasonably acceptable. PMID- 7884259 TI - [Criteria of limited operation for bronchial carcinoid]. AB - The purpose of this study is to establish criteria of limited operation for bronchial carcinoid. Ten cases surgically treated in our hospital and 47 cases reported in Japan from 1981 to 1992 were examined. Thirty-nine cases had typical carcinoid tumor and 18 had atypical. Limited operation, such as pulmonary segmentectomy, wedge resection or partial resection, was performed in 12 cases. In these, all patients of typical type were alive except for a case died of other disease. However, two patients of atypical type died of distant metastasis of the tumor. No lymph node metastasis was revealed in all cases of typical type. On the contrary, in cases of atypical type, six had n1 and two had n2 disease. Moreover, two cases with n1 disease had pulmonary metastasis. Therefore, patients with typical bronchial carcinoid can be cured by limited operation, but radical operation should be indicated for atypical bronchial carcinoid. PMID- 7884260 TI - [Experience of coronary artery bypass grafting with inferior epigastric artery (IEA) and pathological examination of the IEA]. AB - From January to March 1994, coronary artery bypass grafting (CABG) using the inferior epigastric artery (IEA) were performed in 10 patients. The stumps of the IEAs were examined pathologically. 1. Intimal thickening of the IEA was scarcely noted. 2. Internal elastic lamina of the IEA showed good development equivalent to the internal thoracic artery (ITA). 3. Tunica media of the IEA was poor in elastic fibers and rich in smooth muscle cells compared with the ITA. 4. The thickness of intima + media was 150-360 microns, suggesting its low risk of ischemic necrosis in case of free grafting. These results suggested the IEA to be a good graft material applicable for CABG. PMID- 7884262 TI - [Valve replacement in an infant with congenital mitral stenosis--report of a case which showed hemodynamics similar to that of hypoplastic left heart syndrome in neonatal period]. AB - In the neonatal period, the patient showed severely hypoplastic left ventricle, severe mitral stenosis, patent foramen ovale and patent ductus arteriosus with right-to-left shunting, which resulted in the hemodynamics similar to that of hypoplastic left heart syndrome. However, progressive left ventricular growth was recognized after spontaneous closure of the foramen ovale, and the cardiac catheterization at the age of 6 months revealed almost normal left ventricular volume and systolic forward flow from the left ventricle to the descending aorta. The operation was performed at the age of 7 months under cardiopulmonary bypass with moderate hypothermia and cardiac arrest. The mitral leaflets were thickened and dysplastic, two short papillary muscles were hypertrophic and very closely related, and the chordae were extremely short and fused each other making the interchordal space obstructed. Because the mitral annular diameter (13 mm) was too small for conventional valve replacement, the prosthetic valve (CarboMedics #16) was sewn to the left atrial wall 5 to 10 mm above the mitral annulus. The ductus arteriosus was ligated. The postoperative cardiac catheterization showed residual pulmonary hypertension, but pulmonary vascular response to oxygen inhalation was recognized. We consider that there were two important hemodynamic factors which led to successful biventricular repair in this case. First, early spontaneous closure of the foramen ovale accerelated the left ventricular growth and prevented right ventricular failure resulting from increased pulmonary blood flow. Second, considerable part of the systemic output was supplied through a large ductus arteriosus, and thus over-systemic pulmonary hypertension was avoided. PMID- 7884261 TI - [Surgical repair of valvular diseases in patients over 75 years of age]. AB - From January 1985 through August 1993, 41 patients older than 70 years underwent valvular surgery. In them, 10 patients were older than 75 years old. We evaluated those operative results. First, we classified them into 3 groups; Group A: over 75 y.o. (10 cases), Group B: 70-74 y.o. (31 cases) and Group C: 60-69 y.o. (39 cases, from January 1992 through August 1993). Surgical deaths were 1 case in Group A, and 1 in Group B. Distant deaths were 1 case in Group B, and 2 in Group C. Preoperative cardiac catheterization data showed the progression of cardiac failure in proportion to aging. But postoperative data showed no difference among 3 groups, and the condition was reversible. NYHA classification and cardiothoracic ratio (CTR) showed the same results. In summary, in valvular diseases in patients over 75 years of age, the progression of the condition was recognized but it was reversible. So we conclude that the surgical repair of no influence of age is necessary. PMID- 7884263 TI - [Effect of autologous platelet rich plasma on adult open heart surgery]. AB - To reduce the rate and the volume of homologous blood transfusion, we have used autologous platelet rich plasma (PRP) in adult open heart surgery. From Jan. 1988 to Jun 1992, 191 patients have underwent open heart surgery of coronary artery disease or valvular heart disease in our institution. We divided these patients into two groups: (1) PRP group; autologous PRP was used in 99 cases, (2) C (Control) group; autologous PRP was not used in 92 cases. Patient characteristics of age, sex, body weight, preoperative hematocrit values, preoperative platelet counts, and CPB time were same in these groups. Intraoperative and postoperative blood loss in PRP group were significantly less than those in C group (376 ml and 458 ml vs 511 ml and 568 ml; p < 0.01). Homologous blood transfusion rate (number of patients receiving homologous blood transfusion/all patients) was lower in PRP group (11.1% vs 32.6%; p < 0.01). The volume of homologous blood transfusion in the patients receiving transfusion were smaller in PRP group (7.5 U vs 13.3 U; p < 0.05). We conclude autologous PRP is useful in adult open heart surgery to reduce the perioperative blood loss, the rate, and the volume of homologous blood transfusion. PMID- 7884264 TI - [A case of invasive thymoma with myasthenia gravis and pure red cell aplasia]. AB - The patient was a 42-year-old man whose main complaints were ptosis, diplopia and muscle weakness. Chest X-ray film revealed a right hilar mass and chest CT showed a solid mass at right anterior superior mediastinum. Laboratory studies revealed myasthenia gravis (MG) on EMG and pure red cell aplasia (PRCA) on hematology. An extended thymectomy, including the thymoma, was performed. Thrombocytopenia appeared postoperatively, but it improved when a platelet transfusion was given. Steroid was administered for postoperative adjuvant therapy, and the MG and PRCA were alleviated. This rare case of simultaneous MG and PRCA as complications of a thymoma is reported. PMID- 7884265 TI - [Successful cardiac surgery using normothermic cardiopulmonary bypass in an elderly patient with cryoglobulinemia]. AB - The case of 70-year-old woman with cryoglobulinemia who underwent urgent operation for angina pectoris and mitral regurgitation is reported. Three bypass grafts and mitral valvuloplasty were performed under normothermic cardiopulmonary bypass with continuous warm blood cardioplegia. The postoperative course was uneventful. Normothermic cardioplegia requires further study as a technique for managing patients with cold autoimmune diseases such as cryoglobulinemia who require cardiopulmonary bypass. PMID- 7884266 TI - [Successful surgical treatment of active infective endocarditis associated with perforation of aortic wall]. AB - A 69-year-old man was transferred to our hospital because of severe progressive heart failure, eyeground hemorrhage due to embolism and uncontrollable inflammation. Emergent operation was suggested. Aortic valve replacement with a 23 mm Carpentier-Edwards bioprosthesis and patch closure of perforation using Dacron double velore was successfully performed. Vegetation was observed from the commissure between left and non coronary cusp to the aortic wall. Perforation (3 mm in diameter) and a moderate amount of bloody pericardial effusion were recognized. However periannular abscess was not detected. Postoperative course was uneventful and no recurrence of infection has been seen. We believe that surgical treatment for active infective endocarditis should be recommended when the bactericidal agents are ineffective and before the hemodynamics is suddenly deteriorated and the embolism occurs to the other organs. PMID- 7884267 TI - [A case report of acute pulmonary valve endocarditis caused by fungi]. AB - A 42 years old female was admitted for evaluation of unrelenting fever and dyspnea on exertion in March, 1991. The patient had a VSD closure in 1968. After admission, serial blood cultures were found to be positive for Candida Parapsilosis and a massive vegetation on the pulmonary valve was demonstrated by echocardiography. Chest X-ray disclosed a wedge-shaped density in the right middle lung lobe that was a compatible finding with pulmonary infarction. At surgery, performed 3 days later the admission, pulmonary valve was entirely resected without replacing it with prosthesis. Antifungal treatment was intensively given afterwards. Her postoperative course was without event and she was sent home on the 51st postoperative day. Right heart catheterization done two years surgery, revealed the pulmonary vascular resistance was 216 dynes sec cm-5. We anticipate that this degree of pulmonary vascular resistance will allow the patient enough to do well without needing valve prosthesis in the near future. PMID- 7884268 TI - [A case of metachronous primary cancer of the lung, rectum and trachea]. AB - We reported a metachronous primary triple cancer of lung, rectum and trachea. Patient was a 64-year-old male, who was admitted with a episode of bloody sputum. A chest X-ray and rentogen tomogram showed a irregularity and narrowing of the upper trachea. Transbronchoscopic biopsy specimen showed squamous cell carcinoma. December '92, trachea was resected in the length of five cartilages and end-to end anastomosis was performed. Microscopic examination demonstrated a moderately differentiated squamous cell carcinoma with mediastinal lymph node metastasis. Therefore, he received a course of 30 Gy of radiation to the upper mediastinum after surgery. Three years before the tracheal resection, he had undergone left pneumonectomy for moderately differentiated squamous cell carcinoma of the lung. Nineteen months after the pulmonary resection, he had undergone low anterior resection of the colon for the rectum carcinoma. PMID- 7884269 TI - [One and one half ventricle repair for pure pulmonary atresia--a case report]. AB - One and one half ventricle repair consisting of the Glenn operation and the right ventricular outflow tract reconstruction was performed in a 4-year-old boy. The diagnosis of this patient was pure pulmonary atresia. He had undergone Brock's operation, Blalock-Taussig shunt and a central shunt at neonatal period. At the time of one and one half ventricle repair, the connection between the superior vena cava and the right atrium was left open. Although the RVEDV was 34.3% of normal, the topology of the right ventricle was tripartite. At three months after one and one half ventricle repair, RVEDV increased up to 52.7% of normal. This data suggests that a further definitive surgery, i.e., complete biventricular repair could be applicable in the future. PMID- 7884270 TI - [A case report of chronic traumatic thoracic aneurysm (thrombotic closure type) which appeared as a mediastinal tumor in preoperative findings]. AB - Chronic traumatic thoracic aneurysm is considered to be an uncommon disease. A case of 59-year-old man who had a history of blunt chest trauma with a traffic accident thirty years ago is reported. He has no symptoms and no signs since the accident. The roentogenogram of his chest showed widening of upper mediastinum, but aortography did not reveal the aneurysmal dilatation of the aortic arch. CT and MRI study showed an inhomogenous mediastinal tumor simulating neoplasm neighboring the aortic arch. At surgery, it was found to be a thoracic semispherical pseudo-aneurysm (thrombotic closure type) measuring 3 cm diameter with slightly hard fibrous tissue contained aseptic brownish fluids. Following partial clamping of the aorta, the thoracic pseudo-aneurysm was opened and the direct closure of the aortic tear with teflon felt was performed. It is important to check the presence of the thoracic pseudo-aneurysm for following-up the patient after the thoracic trauma. PMID- 7884271 TI - [A case of hemothorax occurred two months after graft replacement of descending thoracic aorta with Hemashield arterial prosthesis]. AB - A 70-year-old man performed graft replacement of descending thoracic aorta for chronic aortic dissection (DeBakey IIIb) with Hemashield arterial prosthesis. He also had coronary artery disease (LAD seg. 7.99% stenosis) and he had received PTCA prior to operation. He was administered anticoagulants such as Aspirin and Warfarin postoperatively. Two months after operation, he complained dyspnea and came back to our hospital. Chest X-ray showed left hemothorax. CT scan and aortogram could not revealed bleeding points such as pseudoanerysm at anastomosis site nor new dissection. He recovered after discontinued anticoagulants and drainage. If you need to use the anticoagulants after graft replacement with Hemashield, you should administer the anticoagulants about 14 days after operation. This is the first clinical report that hemothorax occurred two months after graft replacement with Hemashield. PMID- 7884272 TI - [Biosynthesis of the GPI anchor]. PMID- 7884273 TI - [A new development in isoprenoid biochemistry brought by the discovery of prenylated proteins]. PMID- 7884274 TI - [Three-dimensional structure of an extracellular calcium binding protein, protein S. spore adhesion in myxobacteria]. PMID- 7884275 TI - [Cerebellar long-term memory and gene expression]. PMID- 7884276 TI - [Structure and function of nonmuscle myosins]. PMID- 7884277 TI - [Induction of stress proteins in the endoplasmic reticulum of Saccharomyces cerevisiae]. PMID- 7884279 TI - [Archaebacteria and evolution of life: recent progress in the research]. PMID- 7884278 TI - [How does calmodulin express Ca(2+)-signals--recent progress by solution X-ray scattering]. PMID- 7884280 TI - [Structure and function of a multi-functional protein "clusterin" which inhibits the polymerization of amyloid beta of Alzheimer's disease]. PMID- 7884281 TI - Use of semiquantitative reverse transcription-polymerase chain reaction to study gene expression in normal human skin fibroblasts following low dose-rate irradiation. AB - One way to study the effect of radiation on gene expression is to monitor changes in the levels of specific messenger RNAs. We describe the use of reverse transcription-polymerase chain reaction (RT-PCR) analysis, a faster and more sensitive procedure than the traditional techniques to monitor RNA levels. Using RT-PCR, we confirmed previous results showing increased levels of GADD45 transcripts after high dose-rate X-irradiation in normal human fibroblasts. No differences were observed in the transcript levels of beta-ACTIN, beta MICROGLOBULIN, Cu-Zn SUPEROXIDE DISMUTASE (SOD-1) and CATALASE. In cells exposed to 3-6 Gy low dose-rate gamma-irradiation we observed increased levels of the GADD45 transcript and lower transcript levels of the genes TOPOISOMERASE II alpha, FACC, CYCLIN A and CYCLIN B. No differences were detected in the transcript levels of beta-ACTIN, beta-MICROGLOBULIN, SOD-1, URACYL-DNA GLYCOSYLASE, CYCLIN C, CYCLIN E, CYCLIN D1, CYCLIN D2, CYCLIN D3, TOPOISOMERASE I and TOPOISOMERASE II beta. PMID- 7884282 TI - A knowledge-based model of DNA hydration. AB - The aqueous hydration of DNA is an important aspect of its structure, which is of direct relevance to mechanisms of radiation damage. We have made a quantitative analysis of solvent interactions within hydrogen bonding distance of polar atoms of oligonucleotides using 12 B-DNA oligonucleotide crystal structures. The distribution of water molecules around the four bases, the sugar residues and the phosphate groups were generated and analysed both qualitatively and quantitatively. These data have then been used in a knowledge-based method to generate the likely hydration sites around a canonical B-DNA conformation in order to generate models of use in track studies of radiation damage. PMID- 7884283 TI - Use of pulsed-field gel electrophoresis to investigate factors influencing the measurement of DNA double-strand breaks in human brain tumour specimens. AB - We used pulsed-field gel electrophoresis combined with densitometry to investigate variables influencing the measurement of DNA double-strand breaks (dsb) in human brain tumour cells and frozen tissue. Our studies showed that this system worked best when we ran the gel at 60 V for 22-25 h at 18 degrees C with a pulse time of 15 s in 1xTris-acetic acid-EDTA buffer. Because the densitometric analysis worked well only when DNA concentrations were within a certain range, we developed a quick assay using a DNA-specific dye (TO-PRO-1) to determine concentrations before making agarose plugs. When we used our optimal procedure to measure dsb in six frozen human brain tumour specimens, we found that radiation resistant tumours had significantly more initial dsb than did radiation-sensitive tumours. The number of residual dsb could not be ascertained because the process of freezing the specimens destroyed dsb repair ability. PMID- 7884284 TI - Separation of DNA fragments induced by ionizing irradiation using a graded-field gel electrophoresis. AB - A method is described that allows a separation of X-ray induced DNA fragments by graded-field gel electrophoresis. Synchronized G1 and asynchronous CHO cells were embedded in agarose and irradiated with X-ray doses ranging from 1 to 100 Gy. Following proteolysis by sarcosine and proteinase K, electrophoresis was run for 49 h using graded electric fields with stepwise increasing field strength (0.6, 1.5, 3 and 9 V/cm). Since the molecular size of DNA able to migrate decreased with increasing voltage, each voltage step led to the generation of a distinct DNA band with the largest fragments in band 1, fragments of intermediate size in bands 2 and 3 and the smallest fragments in band 4. Using yeast chromosomal DNA as a reference, the molecular weight of eluted fragments was calculated to range from 1 to 10 Mbp. It could be shown that the fragment size was not the only criterion that discriminates migrating from non-migrating DNA. DNA fragments were found to be retained in the well by an unknown factor presumably associated with DNA conformation. This retention factor increased with increasing fragment size. Graded-field gel electrophoresis also allowed the determination of the absolute number of double-stranded breaks (dsb) induced, which amounted to 11.5 x 10(-12) dsbs Gy-1 Da-1 corresponding to 37 dsbs/G1 cell. PMID- 7884285 TI - Radiation-induced damages in single- and double-stranded DNA. AB - In the present study, we searched for possible effects of DNA strandedness (single and double), on two types of damages, frank strand breaks (FSB, observed at neutral pH) and alkali labile sites (ALS, leading to breaks at alkaline pH) induced by irradiation with gamma-rays (60Co) or fast neutrons (p34,Be). Sequencing gel electrophoresis allowed us to follow the occurrence of these damages at each nucleotide site in single (ss-ss), double (ds-ds), and half single-half double (ss-ds and ds-ss) stranded oligonucleotides. Globally, in DNA with random sequences of bases, no differences in FSB and ALS yield between the single and the double-stranded conformations were observed. One observes, however, an increased alkaline lability at some guanine sites belonging to single stranded region of ss-ds or ds-ss. Nevertheless, strandedness influences the radiosensitivity of some particular sequences, i.e. the 5'-AATT sequences. This region is less radiosensitive than the rest of DNA in the double helical, but not in the single-stranded conformation. The results are discussed in terms of DNA conformation. PMID- 7884286 TI - Chromosome alterations that correlate with progression to immortality in Syrian hamster embryo cells transformed by gamma-irradiation. AB - Primary Syrian hamster embryo (SHE) cells can be transformed in vitro by gamma irradiation or spontaneously and display morphological alterations in discrete colonies as the earliest recognizable transformants. These morphologically transformed colonies can progress to give rise to immortal cell lines. The purpose of the present study was to determine if specific chromosome changes occur that correlate with immortalization. In the non-irradiated culture, 18 transformed colonies were isolated, of which two became immortal. In the irradiated culture, six out of 18 transformed colonies isolated progress to immortalization. Seven out of eight immortalized cell lines exhibited either numerical and/or structural chromosome alterations. Of six radiation-induced immortal lines, four lines showed rearrangements in the long arms of chromosome 3 (3q +) and chromosome 6 (6q +) non-randomly. In all cases, both 3q + and 6q + were detected in the primary transformed colonies from which the immortal cell lines arose. Both 3q + and 6q + occurred always as heterozygotes in the primary transformed colonies. 3q + and 6q + were never found in the non-irradiated culture, demonstrating that these chromosome changes were induced by irradiation. 3q + and 6q + may correlate with progression to immortality in SHE cells transformed by gamma-irradiation. PMID- 7884287 TI - Occupational exposure to radiation induces an adaptive response in human lymphocytes. AB - The in vitro pretreatment of phytohaemagglutinin stimulated human lymphocytes with tritiated thymidine or with low doses of X-rays induces a response that makes these cells less susceptible to further genetic damage induced by subsequent high doses of radiation. This phenomenon has been called 'Adaptive Response' because it is similar to the one described in E. coli. In the present study, we describe that lymphocytes irradiated in vitro at 2 Gy, from individuals occupationally exposed to X and gamma rays, show lower frequencies of dicentrics than those from non-occupationally exposed individuals irradiated in the same conditions. Our results could indicate that an adaptive response can also be induced in lymphocytes in vivo by very low occupational doses of radiation, and that for biological dosimetry purposes it is necessary to know the individual's history of exposure to mutagens. PMID- 7884288 TI - Flow cytometric analysis of micronuclei in the CD2+/- subpopulation of human lymphocytes enriched by magnetic separation. AB - An improved flow cytometric method for the scoring of micronuclei in human lymphocytes irradiated in vitro is presented. Because, especially in cultivated human lymphocytes, unspecific DNA-containing debris from dying cells can influence the measured frequency of micronuclei, a preselection of CD2 + population was performed before preparation of the suspension of micronuclei and nuclei. Magnetic separation using anti-CD2 antibody-conjugated magnetic beads were used for this purpose. The results obtained by this improved flow cytometric technique were compared with results obtained by microscopic scoring using the CB technique. No correlation was found when the individual values in unirradiated controls were compared, due mainly to the presence of DNA-containing particles from fragmented cell nuclei and other unspecific debris. The averaged data from nine dose-effect curves simultaneously analysed by both techniques showed a linear-quadratic dose dependence with alpha and beta's that were similar for flow cytometry and for microscopic scoring. Only the constant term was higher for the flow cytometric results. A correlation between both techniques applied to individual data at doses > 0.2 Gy could also be demonstrated. It is concluded that a dose estimation of man exposed to low doses of ionizing radiation can at present not be improved by the flow cytometric technique. PMID- 7884289 TI - Heat-induced intranuclear protein aggregation and thermal radiosensitization. AB - In the current study, the hypothesis that thermal radiosensitization is (indirectly) caused by heat-induced denaturation and aggregation of nuclear proteins is further investigated. Thermotolerant rodent cells showed a reduced intranuclear protein aggregation as compared with non-tolerant cells immediately after a heat treatment. This was reflected in the extent of radiosensitization when the cells were X-irradiated immediately after a heat treatment. When heat and radiation were separated in time, a faster disaggregation was found in thermotolerant cells, which was paralleled by a more rapid decline of radiosensitization. Cells transfected with hsp72 showed protection against heat induced nuclear protein aggregation and reduced thermal radiosensitization. Transfection with hsp27 resulted in an accelerated nuclear protein disaggregation and accelerated decline of thermal radiosensitization. Despite a significant overall correlation between TER and nuclear protein aggregation, the slopes of the correlation curves for the individual cell lines deviated significantly. Yet, the experiments support the hypothesis that radiosensitization is primarily caused by inhibition of DNA repair as a result of the presence of denatured and aggregated proteins in the cell nucleus. Expression of hsps (e.g. in thermotolerant cells), by affecting nuclear protein aggregation, can have an impact on thermal radiosensitization. PMID- 7884290 TI - Does tirapazamine (SR-4233) have any cytotoxic or sensitizing effect on three human tumour cell lines at clinically relevant partial oxygen pressure? AB - Solid human tumours contain areas with low oxygen tension (pO2). For bioreductive drugs it is important to define the cytotoxic effect according to drug concentration and to clinically relevant pO2. In this study, the pO2 dependence of the survival of three human cell lines (HRT 18, Na11 +, and MEWO), exposed to tirapazamine (SR-4233) alone or combined with ionizing radiation, was studied in vitro. Gas changes were made to obtain five different oxygen concentrations: air (20.9% O2), 10, 2, 0.2 and 0.02% O2 (hypoxia). Tirapazamine below a concentration of 100 microM was not cytotoxic in air or at 10% O2. At 100 microM tirapazamine was toxic in 2% O2, and at 50 microM in 0.2% O2. For pO2 < 0.2% O2, there was a marked increase in cell killing when 10 microM tirapazamine was combined with 2 Gy, compared with either 10 microM or 2 Gy given alone (p < 0.03). The cytotoxic effect of tirapazamine on human tumour cells in vitro is highly dependent on clinically relevant pO2's. The activation of tirapazamine at a low concentration and at a pO2 found mainly in tumours could yield a very beneficial therapeutic ratio. PMID- 7884291 TI - Postnatal neurophysiologic effects of prenatal X-irradiation. AB - Histological and neurophysiological effects of in utero irradiation were examined following exposure of pregnant Wistar rat to 2.0 Gy X-irradiation or sham irradiated on the 17th day of gestation. The 234 newborns were monitored for the age of appearance of four selected physiologic markers and the age of acquisition of five selected reflexes. Offspring were evaluated as young adults using selected behavioural tests. Postnatal growth was monitored weekly. Selected offspring were autopsied to determine the presence of morphologic central nervous system alterations. The results indicated that 2.0 Gy X-irradiation during the foetal period in rat gestation caused permanent alterations in the mature adult organism, which include non-recuperable growth retardation, morphologic changes in the brain such as microcephaly, abnormal cerebellar cortical cellular patterns, and alterations in the cell architecture of the hippocampus; diminished attainment of selected reflexes; alterations in the appearance of selected physiologic markers; and changes in adult test performance indicating significant hyperactivity among the irradiated offspring. Such exposure to X-irradiation during this period results in behavioural and morphologic alterations, which persist throughout life. PMID- 7884292 TI - Bis-dithiocarbamates: effective chelating agents for mobilization of polonium-210 from rat. AB - The time dependence of organ distribution and excretion of intravenously (iv) injected 210Po was investigated after the single or repeated administration of N,N'-diethylamine-N-carbodithioate (diethyldithiocarbamate, DDTC) and three bis dithiocarbamates: N,N'-dimethylethylenediamine-N,N'-biscarbodithioate (MeTTC), N,N'-diethylethylenediamine-N,N'-biscarbodithioate (EtTTC), and N,N' di)20hydroxyethyl)ethylenediamine-N,N'-biscarbodithioate++ + (HOEtTTC). The biokinetics of iv injected 210Po was used as a model for the behaviour of 210Po absorbed into the blood from any other site of entry into the body. The most effective chelating agent was HOEtTTC, which was not only effective when injected subcutaneously (sc) immediately after 210Po, but also 1 h later. Toxic effects of DDTC were observed in a metabolic study when the effect of HOEtTTC was compared with that of DDTC. DDTC caused accumulation of 210Po in brain and transiently in liver. When HOEtTTC was administered, the faecal excretion of 210Po was increased from the very beginning. MeTTC, EtTTC and N-(2,3-dimercaptopropyl)phtalamidic acid (DMPA) were ineffective when the treatment started 1 h after iv injection of 210Po. PMID- 7884293 TI - Neuropathic spinal arthropathy: a case history and six year follow-up. AB - Neuropathic spinal arthropathy is a rare but well-reported sequela of tabes dorsalis. It is now more frequently seen as a complication of spinal cord injury- particularly after spinal fusion. With improved longevity of spinal cord injured patients we are seeing this entity in increased frequency. Clinical and radiographic aspects are described, and a case history is depicted. Classic treatment has been conservative. Based on the changing nature of its etiology and favorable reports from large centers we advocate anterior and posterior fusion and instrumentation of Charcot's Spine. PMID- 7884294 TI - Clinical significance of mycobacterium other than tuberculosis isolated from respiratory specimens at a university hospital. AB - BACKGROUND: Mycobacteria other than tuberculosis (MOTT) are ubiquitous and have been recognized to cause pulmonary disease. Because of newer laboratory diagnostic techniques, it has become more frequent to identify MOTT from pulmonary specimens. The objective of this study was to determine the spectrum of MOTT in pulmonary specimens in hospitalized patients and determine their clinical significance. METHODS: A retrospective study of all cases of positive pulmonary specimens cultured for MOTT in patients admitted to University of Louisville Hospital from January 1989 to December 1992 was performed. A determination of whether or not the MOTT caused pulmonary disease was made, using the criteria required by the American Thoracic Society. RESULTS: There were 221 positive pulmonary specimen cultures for mycobacteria, of which 164 were MOTT and 57 were M tuberculosis. Of the MOTT isolates, 82 (50%) were M gordonae; 44 (27%) M avium intracellulare; 18 (11%) M chelonae; 12 (7%) M fortuitum; 2 (1%) M kansasii; 2 (1%); M scrofulaceum; 2 (1%) M xenopi; and 2 (1%) M terrae. From all the MOTT cases, only one met the criteria for MOTT pulmonary disease. The rest were found to be non-pathogens, either colonizers or contaminants. CONCLUSION: Newer laboratory diagnostic techniques are improving isolation and identification of MOTT. Even though reports of positive pulmonary specimens for MOTT are becoming more numerous, MOTT was found to be a rare pulmonary pathogen in our hospital, when strict criteria were used. PMID- 7884295 TI - An alternate method for intercostal blockade for the management of post herpetic neuralgia. PMID- 7884296 TI - Stand up comedy and the practice of medicine. PMID- 7884297 TI - The "Mother of Rowan County" named Country Doctor of the Year. PMID- 7884298 TI - Effects of direct instruction in Spanish phonology on the native-language skills and foreign-language aptitude of at-risk foreign-language learners. AB - This study examined the effect of an academic year of direct instruction in the phonology/orthography of Spanish on the native-language skills and foreign language aptitude of high school women identified as at risk (n = 14) and not at risk (n = 19) for experiencing problems with learning a foreign language. At-risk students received a specialized teaching approach; not-at-risk students received traditional foreign-language instruction. Pre- and posttest results showed that both groups improved significantly on a foreign-language aptitude test, and the at-risk group made significant gains on native-language phonology/orthography measures. Pretest comparisons showed significant between-group differences on several phonological/orthographic measures and the foreign-language aptitude test. Posttest comparisons showed that the not-at-risk subjects still scored significantly higher than at-risk subjects on the foreign-language aptitude measure; no differences were noted on two native-language phonological/orthographic measures. Pre- and posttest comparisons between groups showed that the at-risk group made significantly greater gains than the not-at risk group on phonological/orthographic measures. Implications for instruction are presented. PMID- 7884299 TI - The career success of an adult with a learning disability: a psychosocial study of amnesic-semantic aphasia. AB - B.I. is a 39-year-old, intellectually gifted (IQ = 130) man with learning disabilities who, without known cause, demonstrated symptoms of amnesic-semantic aphasia at age 13. This led to placement in a public school class for students with mild mental retardation and to his dropping out of school after repeating Grade 9. His aphasia is associated with a severe deficit in speech comprehension, poor reading and writing, spatial confusion, and episodic memory loss. We studied the remarkable behavioral and cognitive adjustments that have enabled him to lead a fulfilling life and become a highly successful business executive. Implications are discussed in the context of patterns of successful functioning and current views of the neuropsychological and neurological bases of such disorders. PMID- 7884300 TI - An experiment on cognitive remediation of word-reading difficulty. AB - Cognitive remediation of decoding deficit was attempted by following a theoretically based program. The theory identifies four major cognitive processes: Planning, Attention, Simultaneous, and Successive (PASS) processing. The PASS Remedial Program (PREP) provides 10 structured tasks that are aimed at developing internalized strategies for mainly successive processes (6 tasks) and simultaneous process (4 tasks); deficits in either of the two may lead to poor decoding. Through its "global process" training and curriculum-related "bridging" training, PREP facilitates application of internalized strategies arrived at inductively for learning word decoding and spelling; it does not provide direct teaching of rules or exercises. To test the efficacy of PREP, we divided 51 children with decoding difficulties in Grade 4 into two groups: PREP (both global and bridging) and no treatment. In the second part of the study, children from the no-treatment group received either the global or the bridging part of PREP. The relative efficacy of training was tested by pre-, and posttests of performance on a standard word-decoding test (the WRMT-R), as well as on some cognitive tests (e.g., the CAS). The largest improvement in word decoding occurred for the PREP combined global and bridging treatment. The mechanism through which PREP improves word reading is discussed, as is the use of PREP for children at risk of developing dyslexia. PMID- 7884301 TI - Developmental right-hemisphere syndrome: clinical spectrum of the nonverbal learning disability. AB - We report the clinical characteristics of the developmental right-hemisphere syndrome (DRHS), a nonverbal learning disability, in 20 children (9 girls and 11 boys; mean age = 9.5 years) who also manifested attention-deficit/hyperactivity disorder (ADHD), severe graphomotor problems, and marked slowness of performance. Diagnostic criteria for this study included (a) emotional and interpersonal difficulties; (b) paralinguistic communication problems; (c) impaired visuospatial skills, verbal IQ > performance IQ, and verbal IQ > or = 85; and either (d) dyscalculia or (e) neurological signs on the left side of the body. In this group, verbal IQ was significantly higher than performance IQ (106.6 +/- 13.0 vs. 85.1 +/- 13.1, respectively, p < .01). Arithmetic was the lowest score among the verbal subtests (7.8 +/- 3.5, p < .01) and Geometrical Design was the lowest score among the performance subtests (5.8 +/- 1.7). Thirteen children had soft neurological signs on the left side of the body. ADHD was seen in all 20 children, marked slowness of performance in 16, and severe graphomotor problems in 18. The latter two features have not been previously described as part of DRHS. PMID- 7884302 TI - Teachers' attitudes toward increased mainstreaming: implementing effective instruction for students with learning disabilities. AB - To investigate the types of instructional strategies offered in mainstream classes, we asked 127 mainstream teachers in Grades 1 through 8 to complete a self-evaluation concerning instructional strategies used in their general education classes. Also, each teacher completed questionnaires concerning their attitudes toward their own efficacy and toward mainstreaming. ANOVAs comparing teachers with positive attitudes toward mainstreaming and teachers with less positive attitudes indicated that the teachers with less positive attitudes used effective mainstream instructional strategies less frequently. Implications of these results in terms of recent educational initiatives resulting in increased inclusion programs are discussed. PMID- 7884303 TI - Comorbidity of reading and mathematics disabilities: genetic and environmental etiologies. AB - Although children with learning disabilities frequently manifest comorbid reading and mathematics deficits, the cause of this comorbidity is unknown. To assess the extent to which comorbidity between reading and mathematics deficits is due to genetic and environmental influences, we conducted a twin study of reading and mathematics performance. Data from 148 identical and 111 fraternal twin pairs in which at least one member of the pair had a reading disability were subjected to a cross-concordance analysis and also fitted to a bivariate extension of the basic multiple regression model for the analysis of selected twin data. Results of these analyses suggest that genetic and shared-environmental influences both contribute to the observed covariance between reading and mathematics deficits. PMID- 7884304 TI - Interleukin-9 and its receptor: involvement in mast cell differentiation and T cell oncogenesis. AB - Interleukin-9 (IL-9) is a multifunctional cytokine produced by activated TH2 clones in vitro and during TH2-like T cell responses in vivo. The IL-9 receptor is a member of the hemopoietin receptor superfamily and interacts with the gamma chain of the IL-2 receptor for signal transduction. Various observations indicate that IL-9 is actively involved in mast cell responses by inducing the proliferation and differentiation of these cells. The role of IL-9 in T cell responses is less clear. Although freshly isolated normal T cells do not respond to IL-9, this cytokine induces the proliferation of murine T cell lymphomas in vitro and in vivo overexpression of IL-9 results in the development of thymic lymphomas. In the human, the existence of an IL-9-mediated autocrine loop has been suggested for some malignancies such as Hodgkin's disease. Other potential biological targets for IL-9 include B lymphocytes, hematopoietic progenitors, and immature neuronal cell lines. PMID- 7884305 TI - Review of the macrophage disappearance reaction. AB - Macrophages (M phi s) undergo a physiological response known as the macrophage disappearance reaction (MDR) in response to certain stimuli in the peritoneal compartment. The types of stimuli that can cause the MDR, the relationship of the MDR to the host immunological response, and the possible role of the MDR in M phi activation are reviewed. The data indicate that the MDR occurs in response to both acute nonspecific inflammatory and specific immune delayed hypersensitivity processes and that the MDR may play an important role in M phi activation. PMID- 7884306 TI - Intercellular adhesion molecule 1 (ICAM-1) expression and its role in neutrophil induced ischemia-reperfusion injury in rat liver. AB - The potential role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of reperfusion injury was investigated in male Fischer rats subjected to 45 min of hepatic ischemia and 24 h of reperfusion. ICAM-1 mRNA levels increased during ischemia in the ischemic liver lobes; however, during reperfusion mRNA levels increased in both the ischemic and nonischemic lobes. Immunohistochemical evaluation indicated ICAM-1 expression only on sinusoidal lining cells in controls; ischemia-reperfusion enhanced ICAM-1 expression in the sinusoids and induced some expression on hepatocytes. The monoclonal anti-ICAM-1 antibody 1A29, but not an immunoglobulin G control antibody, administered at 1 h and 8 h of reperfusion (2 mg/kg) significantly attenuated liver injury as indicated by 51% lower plasma alanine aminotransferase activities and 32-36% less hepatic necrosis at 24 h without affecting reactive oxygen formation by Kupffer cells and hepatic neutrophils. Although 1A29 reduced neutrophil extravasation in a glycogen peritonitis by 60%, the antibody had no significant effect on hepatic neutrophil infiltration during reperfusion. These data suggest that ICAM-1 plays a significant role during the neutrophil-dependent injury phase after hepatic ischemia and reperfusion and therefore blocking this adhesion molecule may have therapeutic potential against postischemic acute liver failure. PMID- 7884307 TI - Free-form neutrophil elastase is an independent marker predicting recurrence in primary breast cancer. AB - We have measured the immunoreactive neutrophil elastase (ir-NE) concentration in tumor extracts of 313 primary human breast cancers using an enzyme-linked immunosorbent assay recently developed and have evaluated its association with disease-free survival. This is a sensitive assay that enables rapid measurement of both free-form and alpha 1-proteinase inhibitor (alpha 1-PI)-complexed form of ir-NE. Breast cancer patients with high ir-NE concentrations had a significantly shorter disease-free survival (P = .013) than those with a low ir-NE concentration at the cutoff point of 9.0 micrograms/100 mg protein, which was determined in another group of 49 patients. In multivariate analysis, the ir-NE level was found to be an independent prognostic factor (relative risk = 2.2, P = .025) for disease recurrence in human breast cancer. Furthermore, when multivariate analysis was repeated with inclusion of each level of free-form and alpha 1-PI-complexed form, the former level was an independent predictor of recurrence (relative risk = 2.5, P = .015), whereas the latter was not independently predictive (P = .43). These results support the hypothesis that this enzyme may play an active role in the tumor progression that leads to metastasis in human breast cancer. PMID- 7884308 TI - Secreted glucocorticoids regulate leukocyte-endothelial interactions in inflammation. A direct vital microscopic study. AB - Leukocytes come into intimate contact with the venular endothelium as they extravasate from blood to the interstitium during inflammation. In exteriorized tissues, the number of leukocytes rolling along the vessel wall was markedly increased in adrenalectomized and metyrapone-treated animals, relative to sham operated and normal animals. During the development of an acute, local inflammatory response, rollers were numerically decreased and a stronger adhesion of the cells to the endothelium, with a concomitant migration into tissues, was observed. Adhesion and migration were much more marked in adrenalectomized and metyrapone-treated animals than in controls, suggesting that secreted glucocorticoids exert a suppressive effect on leukocyte-endothelial interactions. The increased number of rolling leukocytes in adrenalectomized and metyrapone treated animals apparently resulted in more cells available to migrate into inflamed tissues. The effect appears to involve receptor occupancy and induction of gene expression because normal animals receiving the steroid antagonist RU 38 486, actinomycin D, or cycloheximide behaved as adrenalectomized or metyrapone treated animals. Administration to adrenalectomized animals of a monoclonal antibody to the membrane glycoprotein complex CD18 did not affect the number of rolling cells, but dramatically reduced the number of adherent or migrated leukocytes. It is suggested that secreted glucocorticoids, in addition to an effect on rolling behavior of circulating leukocytes, might also modulate the activity of the glycoprotein complex CD18 on white blood cells. The ultimate consequence is a restrictive effect on cell emigration in inflammation. PMID- 7884309 TI - Neutrophil activation by anti-beta 2 glycoprotein I monoclonal antibodies via Fc gamma receptor II. AB - Murine monoclonal antibodies (mAbs) to human beta 2-glycoprotein I (beta 2GPI), a plasma protein required for the binding of some antiphospholipid antibodies, have been shown to possess lupus anticoagulant properties and to activate platelets via Fc gamma receptor (Fc gamma R) crosslinking. Here we investigated their ability to induce polymorphonuclear leukocyte (PMN) functional responses. The six mAbs (IgG1 isotype) tested in combination with beta 2GPI led to a concentration dependent activation of human PMNs as appreciated by granule release, H2O2 production, and cytosolic Ca2+ increase. This activation process was accompanied by the enhancement of PMN-mediated heparan sulfate loss from the endothelial cell line EA.hy 926 without evidence for cell lysis or detachment. F(ab')2 fragments of one of the mAbs bound to PMNs in a beta 2GPI-dependent manner but were devoid of activating effects. Carbamylated beta 2GPI was unable to mediate PMN-antibody binding and subsequent activation. In addition, cationization of beta 2GPI or removal of its sialic acid groups led to higher efficiency in binding to the PMN surface and triggering activation in comparison with the untreated protein. Thus, the process of PMN activation depends on mAb binding to these cells through both Fab (via beta 2GPI) and Fc domains, as confirmed by the suppression of all responses upon treatment with an anti-Fc gamma RII, but not anti-Fc gamma RIII, antibody. Our data suggest a model of cellular activation by beta 2GPI-dependent antiphospholipid antibodies. PMID- 7884310 TI - Loss of response to beta-adrenoceptor agonists during the maturation of human monocytes to macrophages in vitro. AB - We have previously reported that human airway macrophages do not respond to the beta-adrenoceptor agonist isoprenaline. The airway macrophage is known to be derived from the blood monocyte. In this study we have assessed the effect of beta-adrenoceptor stimulation on human monocytes matured into macrophages in vitro, to determine whether the lack of response previously observed in the airway macrophage may be a consequence of differentiation. The release of thromboxane B2 (TXB2) from freshly isolated monocytes stimulated by opsonized zymosan (OPZ) was inhibited by 39.3 +/- 5.5% in the presence of isoprenaline (10( 7) M). However, the response was lost in the monocyte-derived macrophage (MDM), where isoprenaline (10(-7) M) caused only 4.0 +/- 9.3% inhibition of OPZ stimulated TXB2 release. In contrast forskolin (10(-5) M) inhibited MDM TXB2 release by 36.4 +/- 17.3%, indicating that the adenylyl cyclase was functional. Measurement of adenylyl cyclase activity showed that there was a reduction in the basal level, 17.03 +/- 4.1 to 7.9 +/- 4.6 cyclic AMP pmol/min/mg protein, and NaF (10(-2) M)-induced activity, 116.3 +/- 32.1 to 21.9 +/- 12.6 cyclic AMP pmol/min/mg protein, between freshly isolated monocytes and MDMs, respectively. In addition, there was no change in MDM basal adenylyl cyclase activity on exposure to isoprenaline. Thus we have demonstrated the loss of beta-adrenoceptor function during the maturation of human monocytes to macrophages in vitro, despite a functional adenylyl cyclase system. In this respect the monocyte derived macrophage is like the airway macrophage. PMID- 7884311 TI - Enhancement in accessibility to macrophages by modification of mucin-type carbohydrate chains on a tumor cell line: role of a C-type lectin of macrophages. AB - We investigated the role of mucin-type (O-linked) carbohydrate chains of tumor target cells in the recognition by macrophages through a Gal/GalNAc-specific calcium-dependent lectin. Binding of a soluble form of this lectin to P815 mastocytoma cells was increased by treatment with benzyl-GalNAc, which presumably inhibited the extension of mucin-type carbohydrate chains. The levels of cell surface expression of GalNAc residues were elevated after benzyl-GalNAc treatment, as revealed by the binding of Vicia villosa agglutinin B4 and Dolichos biflorus agglutinin. Adhesion of treated P815 cells to this lectin immobilized on plastic surfaces also increased. Furthermore, the binding of P815 cells to macrophage-like RAW 264.7 cells and to peritoneal macrophages also increased after the same treatment. We concluded that elevated levels of cell surface terminal GalNAc in mucin-type carbohydrate chains increased accessibility of P815 cells to macrophages through Gal/GalNAc-specific calcium-dependent lectins. PMID- 7884312 TI - Immunocytochemical detection of lipid peroxidation in phagosomes of human neutrophils: correlation with expression of flavocytochrome b. AB - Oxidants generated by the NADPH oxidase of activated neutrophils can react with a number of tissue targets to form toxic metabolites such as 4-hydroxynonenal (4 HNE). 4-HNE is a lipid peroxidation product generated by free radical attack on omega-6 polyunsaturated fatty acids and is a marker for membrane lipid peroxidation. In this study, we examined the accumulation of 4-HNE-protein adducts in phagosomes of neutrophils obtained from a male patient with homozygous X-linked, flavocytochrome b-deficient chronic granulomatous disease (CGD), his heterozygous mother, and his normal father. Specific polyclonal antibodies recognizing 4-HNE-protein adducts and gp91-phox (flavocytochrome b large subunit) were prepared and used to immunocytochemically detect these antigens in cryofixed, molecular distillation-dried neutrophils. No 4-HNE-protein adducts were detected in flavocytochrome b-deficit cells from the homozygous patient or from the heterozygous CGD carrier. However, in gp91-phox-positive cells from both the normal and heterozygous CGD carrier, significant 4-HNE-protein adduct labeling was observed, primarily in the phagosomes. When data from single- and double-labeled cells were combined, the frequency distribution of the labels in phagosomes supported this observation, showing that neutrophils from the heterozygous CGD carrier were 71% 4-HNE-protein adduct-positive and 56% gp91-phox positive, while cells from the normal father were > 97% positive for both 4-HNE protein adducts and gp91-phox. These results confirmed the nitroblue tetrazolium tests of 100%, 60 +/- 2%, and 0% positive for the father's, mother's, and son's cells, respectively, and demonstrated that 4-HNE-protein adduct antibodies are useful and accurate probes of the occurrence of lipid peroxidation in vivo. We conclude that 4-HNE and resulting 4-HNE-protein adducts are generated as a result of NADPH oxidase activity in the phagosomes of human neutrophils and that these lipid peroxidation products may contribute to microbial killing and/or damage of neutrophil phagolysosomal proteins. PMID- 7884313 TI - Distinct actions of benzene and its metabolites on nitric oxide production by bone marrow leukocytes. AB - Benzene is a widely used industrial solvent known to cause bone marrow depression. This is associated with increased production of reactive oxygen metabolites and nitric oxide by bone marrow phagocytes, which have been implicated in hematotoxicity. Benzene metabolism to phenolic intermediates appears to be an important factor in bone marrow toxicity. In the present studies, we compared the effects of benzene and several of its metabolites on nitric oxide production by murine bone marrow leukocytes. Bone marrow cells readily produced nitric oxide in response to the inflammatory mediators lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Treatment of mice with benzene (800 mg/kg), or its metabolites hydroquinone (100 mg/kg), 1,2,4 benzenetriol (25 mg/kg), or p-benzoquinone (2 mg/kg), at doses that impair hematopoiesis, sensitized bone marrow leukocytes to produce increased amounts of nitric oxide in response to LPS and IFN-gamma. Granulocyte-macrophage colony stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) augmented bone marrow leukocyte production of nitric oxide induced by inflammatory mediators. Benzene, as well as its metabolites, markedly increased the sensitivity of the cells to both GM-CSF and M-CSF. Cells from hydroquinone- or 1,2,4-benzenetriol-treated mice were significantly more responsive to the inflammatory cytokines and growth factors than cells isolated from benzene- or p benzoquinone-treated mice, suggesting that the phenolic metabolites of benzene are important biological reactive intermediates. Because nitric oxide suppresses cell growth and can be metabolized to mutagens and carcinogens, the ability of benzene and its metabolites to modulates its production in the bone marrow may be important in their mechanism of action. PMID- 7884314 TI - Effects of oxidized LDL on mononuclear phagocytes: inhibition of induction of four inflammatory cytokine gene RNAs, release of NO, and cytolysis of tumor cells. AB - A critical step in development of atherosclerosis is the interaction of oxidized low-density lipoprotein (LDL) with mononuclear phagocytes. Oxidized LDL, as well as acetyl-LDL, is rapidly taken up into macrophages via a family of scavenger receptors. We report that macrophages treated with oxidized LDL have markedly lower levels of mRNA specific for the genes MCP-1, TNF-alpha, IL-1 alpha, and KC as measured by Northern blot analyses of lipopolysaccharide (LPS)-stimulated macrophages. By contrast, acetyl-LDL does not inhibit these genes at the doses at which oxidized-LDL is effective. Similar effects are observed whether the LDL is oxidized in the presence of Cu2+ or of Fe2+. Such inhibition also occurs when maleylated bovine serum albumin (BSA), which also clears by one or more scavenger receptors on macrophages, is used as the stimulant. Fe2+ or Cu2+ oxidized LDL inhibits release of nitric oxide when triggered by LPS and direct cytolysis of tumor cells when triggered by maleylated BSA or LPS. Taken together, the data presented indicate that oxidized LDL inhibits induction of several important gene RNAs as well as functional markers that characterize the development of inflammatory and fully activated macrophages. PMID- 7884315 TI - Normal human sweat contains interleukin-8. AB - Sweating in humans is induced by physical or emotional stress, which raises the possibility that sweating may relate to host defense. We therefore asked whether human eccrine sweat attracts leukocytes and found that it is chemotactic for human neutrophils. This activity was due to several chemoattractants, one of which was interleukin-8 (IL-8). Using immunohistochemistry and in situ hybridization IL-8 and its mRNA have been detected in sweat gland epithelium, indicating that IL-8 is produced in situ. This establishes a pattern of physiological IL-8 secretion by exocrine glands and suggests that, in addition to its role as a major inflammatory mediator, IL-8 also has physiological homeostatic functions. PMID- 7884316 TI - Blood, sweat, and chemotactic cytokines. PMID- 7884317 TI - Differential inhibitory effects of interleukin-10, interleukin-4, and dexamethasone on staphylococcal enterotoxin-induced cytokine production and T cell activation. AB - The cytokine profile of human peripheral blood mononuclear cells (PBMC) stimulated by staphylococcal enterotoxin (SE) A and B was examined. Production of tumor necrosis factor (TNF alpha), interleukin (IL)-1, IL-6, IL-2, and gamma interferon (IFN-gamma) was observed. In contrast, Th2 cytokines IL-4 and IL-10 were absent from SEA- or SEB-stimulated PBMC. Moreover, adding IL-10 to SE stimulated PBMC inhibited the production of IL-1, IL-6, TNF alpha, and IFN gamma by 50 to 80% but had less effect (8-30%) on T cell proliferation. IL-4 was less effective than IL-10 in inhibiting cytokine production and enhanced T cell proliferation by SEA or SEB. The anti-inflammatory agent, dexamethasone, was the most potent agent in controlling the SE-mediated effects as evidenced by inhibited T cell proliferation (55%) and reduced levels of IL-1, IL-6, and IFN gamma (60% to 100%) and TNF alpha (50%). Reducing levels of toxic mediators such as TNF alpha, IL-1, IL-6, and IFN gamma by dexamethasone in SE-induced T cell responses may be a useful therapeutic strategy to circumvent SE toxicity and pathogenesis. PMID- 7884318 TI - 75- but not 55-kDa tumor necrosis factor receptor is active in the homotypic aggregation and proliferation of human lymphokine-activated T killer (T-LAK) cells in vitro. AB - Lymphotoxin (LT) and tumor necrosis factor (TNF) play important roles in the maturation and growth of human lymphokine-activated T killer (T-LAK) cells in vitro. The role of 55- and 75-kDa TNF receptor (TNF-R) in the aggregation and proliferation of T-LAK cells was investigated using agonistic anti-TNF-R rabbit polyclonal antibodies. Human peripheral blood T cells and T-LAK cells predominantly express 75-kDa TNF-R. The proliferation of T-LAK cells during the generation phase is supported by innate LT and TNF. In this phase, the proliferation was upregulated by anti-75- but not 55-kDa TNF-R antibody. Homotypic aggregation of T-LAK cells was induced by LT, TNF, and anti-75- but not by anti-55-kDa TNF-R antibody. The increase of homotypic aggregation was accompanied by up-regulation of intercellular adhesion molecule 1 but not lymphocyte function-associated antigen 1 expression on cells and by an elevation of membrane fluidity, both of which were up-regulated by anti-75- but not 55-kDa TNF-R antibody. Interestingly, LT and TNF suppressed the proliferation of mature T-LAK cells. Anti-75- but not 55-kDa TNF-R antibody suppressed the proliferation, mimicking LT and TNF. These findings indicated that 75- but not 55-kDa TNF-R is biologically active in the modulation of aggregation and proliferation of human T LAK cells in vitro. PMID- 7884319 TI - Synergism between interferon-gamma and cytokines or lipopolysaccharide in the activation of the HIV-LTR in macrophages. AB - Macrophages (mos) obtained from transgenic mice carrying the HIV long terminal repeat-chloramphenicol acetyl transferase (LTR-CAT) sequence were used to study the influence of various biologic response modifiers (BRMs) on the activation of LTR-directed CAT expression. It was found that LPS or IL-6 alone induced moderate levels of CAT expression, whereas IFN-gamma or TNF-alpha had no significant effect. Co-exposure of mos to IFN-gamma and either LPS, IL-6, or TNF-alpha led to significant synergistic increases in CAT levels. Levels were also synergistically augmented when mos were exposed first to IFN-gamma (priming), washed, and then exposed to either LPS, IL-6, or TNF-alpha. Although IL-6 was synergistic with subsequently added IFN-gamma, the reverse sequence of addition was more effective. LPS and TNF-alpha were inactive when added before IFN-gamma. Initial priming signals were rapid as exposure for 3 h to IFN-gamma was sufficient to prepare the cells for subsequent activation by other BRMs. These results suggest that the duration of latency and progression of HIV infections may be greatly influenced by events such as intercurrent infections that cause IFN-gamma production, thereby priming mos to respond to other cytokines that have been reported to be constitutively elevated during the course of infection with HIV (e.g., IL-6 and/or TNF-alpha). PMID- 7884320 TI - Cloning and characterization of a novel cDNA that is IFN-gamma-induced in mouse peritoneal macrophages and encodes a putative GTP-binding protein. AB - Macrophage activation by IFN-gamma results in a cascade of gene expression. To identify genes activated in mouse peritoneal macrophages by IFN-gamma, we created a cDNA subtraction library of IFN-gamma-induced genes. We have isolated from this subtraction library a novel cDNA clone, called Mg21, whose mRNA is absent in unstimulated mouse peritoneal macrophages and is induced to high levels within 4 h following the addition of IFN-gamma. Induction of Mg21 mRNA by IFN-gamma occurred in the presence of cycloheximide, indicating that expression of Mg21 mRNA does not require protein synthesis. A small amount of Mg21 mRNA was also induced by LPS, but not by IL-2, IL-4, IL-10, or TNF-alpha. The DNA sequence of Mg21 is 1617 nucleotides and contains an open reading frame that codes for a protein of 415 amino acids with a predicted molecular weight of 47,106 Da. The predicted amino acid sequence lacks a signal sequence or transmembrane segments, indicating that the protein is an intracellular protein. Computer search of the GenBank and EMBL databases indicates that this cDNA clone is unique but has 57% sequence identity with IRG-47, which is a mouse gene induced by IFN-gamma in pre B and B lymphocyte cell lines. IRG-47 encodes an intracellular protein that contains three conserved protein motifs present in GTP-binding proteins. Analysis of the protein sequence of Mg21 showed that these three conserved protein motifs are also present in Mg21. PMID- 7884321 TI - Differential regulation of fyn-associated protein tyrosine kinase activity by macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF). AB - The proliferation and differentiation of macrophages are regulated by, among others, GM-CSF and M-CSF. Treatment of bone marrow nonadherent (NA) cells with M CSF induced a greater percentage of NA cells into adherent cells, recognized as monocyte/macrophages, than did GM-CSF. The effect of GM-CSF and M-CSF on the activation of fyn kinase, a 59-kDa src family-related protein tyrosine kinase (PTK), was studied. Control cultures of bone marrow NA cells expressed only minimal levels of fyn kinase activity. Treatment of bone marrow NA cells with M CSF, but not GM-CSF, for 12 to 24 h greatly enhanced the levels of fyn kinase activity. The effect of M-CSF on the activation of fyn kinase was further investigated using bipotential adherent bone marrow-derived macrophages (BMDMs) that coexpress receptors for both GM-CSF and M-CSF. BMDMs can be induced by either growth factor to undergo extensive proliferation in vitro. Compared to bone marrow NA cells, BMDMs displayed higher levels of basal fyn kinase activity, which were similarly elevated by M-CSF but not GM-CSF treatment. The role of fyn kinase in regulating cell adhesion was investigated by growing BMDMs in both tissue culture and Teflon flasks. The growth of BMDMs was anchorage independent; the majority of them continued to proliferate as cell suspension in Teflon flasks. Whereas the levels of fyn kinase activity in adherent BMDMs grown in tissue culture flasks increased steadily, those in BMDMs grown in Teflon flasks diminished. To study the role of fyn kinase in growth regulation, BMDMs were treated with c-fyn sense and antisense s-oligos. In the presence of c-fyn antisense s-oligos, the proliferative response of BMDMs to M-CSF but not GM-CSF was inhibited. In contrast, the proliferation of BMDM in response to either GM CSF or M-CSF was not influenced by c-fyn sense s-oligos. Collectively, our data suggest that the activation of fyn kinase is closely associated with the acquisition of adherent capacity in maturing macrophages. PMID- 7884322 TI - A mouse monoclonal antibody specific for the V beta 5.3 chain of the human TcR recognizes a subgroup of the mouse TcR V beta 8.2 chains. AB - We have analyzed the reactivity of a mouse monoclonal antibody directed against the human T cell receptor for antigen (TCR). This antibody (111-427) of immunoglobulin G1 isotype has been produced in a BALB/c mouse immunized with HPB ALL cells and normal human peripheral blood leukocytes. It reacts specifically with the HPB-ALL lymphoma and 2 to 7% of normal human blood lymphocytes, on which it has a mitogenic effect in vitro. We have shown that it immunoprecipitates the alpha beta TCR of HPB-ALL and that it is specific for the V beta 5.3 chain of the human TCR. In addition, we have observed that this antibody stains a minor fraction of T lymphocytes in different strains of mice. We have screened a number of murine T cell clones or hybridomas and have found that the T cell hybrid line DO.11.10.S4.4 is positive. We have been unable to immunoprecipitate reproducibly the molecule recognized by 111-427 after 125I cell surface labeling and cell lysis in NP-40 or digitonin, probably because of low-affinity binding. On Western blotting, 111-427 revealed one band that has an apparent molecular mass of 89 kDa in nonreducing conditions and disappears after reduction. Similar results were obtained in parallel with the F23.1 and F23.2 antibodies. Thus, this antibody appears to recognize an epitope present primarily on the V beta 8.2 chain of the mouse TCR. We have assayed its capacity to stimulate splenic T lymphocytes in vitro. We have observed that it is capable of triggering, to a minor degree in soluble form and very effectively when coupled to Sepharose beads, the proliferation of spleen T lymphocytes from mice chronically infected with the blood parasite Trypanosoma cruzi. PMID- 7884323 TI - TNF-alpha stimulates increased plasma membrane guanine nucleotide binding protein activity in polymorphonuclear leukocytes. AB - TNF-alpha enhances the response of polymorphonuclear leukocytes (PMN) to chemoattractants: however, the mechanism by which this occurs is unclear. We addressed the hypothesis that TNF-alpha enhances the PMN response to chemoattractants by increasing chemoattractant receptor transmembrane signaling, using fMLP as the model chemoattractant. fMLP-stimulated guanine nucleotide binding (G) protein activation was significantly increased in plasma membranes isolated from PMNs exposed to TNF-alpha 100 U/ml for 10 minutes (TNF-M), compared to membranes from control cells (CM). Formyl peptide receptor number and affinity were not significantly different in CM and TNF-M. Gi and Gs content were increased in TNF-M as measured by pertussis toxin and cholera toxin (CT) catalyzed ADP-ribosylation, respectively. The increased Gi was coupled to the formyl peptide receptor as shown by receptor-specific CT labeling of Gi. Immunoblot analysis showed that both G alpha i2 and G alpha 3 were increased in TNF-M. The functional activity of the increased G protein content was demonstrated by increased NaF-stimulated phospholipase D activity in TNF-alpha treated PMNs. We conclude that TNF-alpha rapidly stimulates increased PMN plasma membrane expression of G proteins that couple formyl peptide receptors to effector enzymes. Regulation of G protein expression may be a significant mechanism by which TNF regulates PMN function. PMID- 7884324 TI - Identification of macrophage activation associated proteins by two-dimensional gel electrophoresis and microsequencing. AB - To understand activation in monocytes and macrophages we have studied changes in protein synthesis using the human monocytoid U937 cell line and two-dimensional polyacrylamide gel electrophoresis (2D PAGE) and protein sequencing. U937 cells that had been metabolically labeled during treatment with PMA, LPS, or IFN-gamma showed appreciable increases or decreases in synthesis of 14 proteins when analyzed by 2D PAGE. Although some 20 proteins are reported to be affected by these agents in U937 cells, none of them correspond with the 14 proteins studied here. Of the 14 observed changes, four spots (p41/65, p35/65, p26/44, p20/53) were up-regulated by PMA only, one (p16/44) by LPS only, five spots (p29/47, p26/45, p26/48, p12/47, p10/45) by both LPS and PMA, and, finally, one (p29/45) by all three agents. Two spots (p20/59 and p20/61) were down-regulated by IFN gamma and one of these spots (p20/59) was up-regulated by LPS. Only one spot (p20/48) was up-regulated by IFN-gamma. Eleven spots with matching mobilities (both M(r) and pI) to those identified in U937 were observed on 2D PAGE gels from human culture derived macrophages. Ten spots from U937 were sequenced by Edman degradation. Two were could not identified from information contained in the available DNA and protein databases and thus represent novel proteins, whereas a further six of the proteins were N-terminally blocked. The remaining two (29/47 and 12/47, respectively) were identified from existing protein databases as translationally controlled tumor protein (TCTP) and cytokeratin. This is the first report of the presence of TCTP in hemopoietic cells and its modulation by PMA or LPS in any cell type. We believe that 2D PAGE and sequencing is a powerful approach for identifying key proteins in macrophage cellular activation. PMID- 7884325 TI - Monoclonal antibody EG2 reactivity cannot be used as an immunohistochemical activation marker for eosinophils. PMID- 7884326 TI - Motions of the head and thorax during neck manipulations. AB - OBJECTIVE: The purpose of this study was to determine the amplitudes and variations of preload positioning and displacements of the head and thorax during spinal manipulative therapy (SMT) applied to C2. DESIGN: This experimental study measured the biomechanics of SMT applied to C2. SETTING: Biomechanics Laboratory, Mechanical Engineering and Applied Mechanics, University of Michigan and Spinal Ergonomics and Joint Research Laboratory, National College of Chiropractic. PARTICIPANTS: Eighteen healthy volunteers from the University of Michigan and the National College of Chiropractic were manipulated by a total of eight experienced chiropractic physicians licensed in the state in which they participated. INTERVENTION: Sixty-six Direct Break (DB) and twenty-three Rotary Break (RB) diversified procedures were administered to C2. Randomization of the DB was made on two variables, direction and intended load intensities. The RB was administered only from the right by each physician. MAIN OUTCOME MEASURES: Linear and angular displacement time histories for the head and thorax mass centers were monitored during the preload setup of each procedure and the dynamic delivery of the treatment procedures. CONCLUSIONS: DB procedures were found to have sagittally symmetric positioning and displacements as a function of intended direction of the procedure. Both DB and RB methods consisted of preload positioning with head flexion. RB rotation and lateral bending preload positions approached the maximal voluntary ranges of motion for the upper cervical spine. Variations among procedures by one manipulator were approximately the same as for variations among manipulators. Data indicates that SMT procedures can be successfully modified to control amplitude and direction of body segment displacements that arise. PMID- 7884327 TI - Attitudes on immunization: a survey of American chiropractors. AB - OBJECTIVE: To assess chiropractic attitudes toward immunization. DESIGN: Random sample survey by mail. PARTICIPANTS: One percent of American chiropractors were surveyed. The response rate was 37%. INTERVENTIONS: Participants were asked to read APHA policy statement "7805: Immunization Against Childhood Diseases" before filling out the survey. MAIN OUTCOME MEASURES: Five-point Likert scales of agreement and disagreement. RESULTS: One-third agree that there is no scientific proof that immunization prevents disease, that vaccinations cause more disease than they prevent, and that contracting an infectious disease is safer than immunization. Eighty-one percent feel immunization should be voluntary and 46% support an official policy against the APHA resolution 7805. ICA members were more likely to agree with negative statements concerning immunization than ACA members. CONCLUSIONS: There is a significant minority of American chiropractors who harbor anti-immunization sentiments despite the weight of scientific evidence supporting its value. Greater efforts must be made by chiropractic educators, associations, and licensing boards to ensure that clinicians base their attitudes on clinical and epidemiological research rather than emotion, rhetoric and dogma. PMID- 7884328 TI - Interexaminer reliability of palpation for cervical spine tenderness. AB - OBJECTIVE: To assess the interexaminer reliability of manual palpation for cervical spine tenderness in neck pain patients. DESIGN: Interexaminer reliability was studied using a within-subjects (repeated measures) design. Seven joints on the symptomatic side of the neck were palpated for maximal tenderness. SETTING: Private chiropractic practice of the Los Angeles College of Chiropractic. PATIENTS: Thirty patients with unilateral mechanical neck pain, symptomatic at the time of examination, were recruited from a chiropractic practice. RESULTS: Good interexaminer reliability (kappa = .68, p < .001, percent agreement 76.6%). CONCLUSION: In this population, palpation for cervical spine tenderness is a highly reliable examination tool. The findings of this study are consistent with those of palpation of the lumbar spine. Further investigation is needed to assess the usefulness of spinal tenderness as an outcome measure, the behavior of tenderness over time, and the prevalence of tenderness in symptomatic and asymptomatic populations. PMID- 7884329 TI - Chiropractic management of primary nocturnal enuresis. AB - OBJECTIVE: To evaluate chiropractic management of primary nocturnal enuresis in children. DESIGN: A controlled clinical trial for 10 wk preceded by and followed by a 2-wk nontreatment period. SETTING: Chiropractic clinic of the Palmer Institute of Graduate Studies and Research. PARTICIPANTS: Forty-six nocturnal enuretic children (31 treatment and 15 control group), from a group of 57 children initially included in the study, participated in the trial. INTERVENTION: High velocity, short lever adjustments of the spine consistent with the Palmer Package Techniques; or a sham adjustment using an Activator at a nontension setting administered to the examiner's underlying contact point. Two 5th-year chiropractic students under the supervision of two clinic faculty performed the adjustments. MAIN OUTCOME MEASURES: Frequency of wet nights. RESULTS: The post-treatment mean wet night frequency of 7.6 nights/2 wk for the treatment group was significantly less than its baseline mean wet night frequency of 9.1 nights/2 wk (p = 0.05). For the control group, there was practically no change (12.1 to 12.2 nights/2 wk) in the mean wet night frequency from the baseline to the post-treatment. The mean pre- to post-treatment change in the wet night frequency for the treatment group compared with the control group did not reach statistical significance (p = 0.067). Twenty-five percent of the treatment group children had 50% or more reduction in the wet night frequency from baseline to post-treatment while none among the control group had such reduction. CONCLUSIONS: Results of the present study strongly suggest the effectiveness of chiropractic treatment for primary nocturnal enuresis. A larger study of longer duration with a 6-month follow-up is therefore warranted. PMID- 7884330 TI - Does obesity cause low back pain? AB - OBJECTIVES: The purpose of this study is to review the recent literature on the association between obesity and low back pain, in an effort to determine whether weight control can be considered an appropriate treatment for low back pain, and whether obesity can be considered a primary etiology of low back pain. DATA SOURCES: We reviewed articles in English from 1970 to present on MEDLINE that listed both obesity and low back pain as key words. Because of the paucity of articles retrieved this way, we also reviewed the bibliographies of each article to draw more studies into our review. Our search generated only seven studies. A standard textbook of obesity was also utilized as a source of basic science of obesity. CONCLUSION: Our review of these articles revealed a possible association between obesity and low back pain only in the upper quintile of obesity, and no evidence of a temporal relationship between weight change and low back pain change. The studies reviewed failed to differentiate low back pain patients by diagnosis and failed to quantify the possible presence of emotional factors in obese low back pain patients. As an incidental finding, one study documented a significant correlation between smoking history and low back pain. We concluded that there is no evidence in the current literature to support obesity that is not in the highest quintile as a cause of low back pain. We recommended that a longitudinal study be done that subclassified obese low back pain patients by mechanical and psychological diagnosis. PMID- 7884331 TI - Manipulation under anesthesia combined with epidural steroid injection. AB - OBJECTIVE: To demonstrate the benefit of cooperation between medical and chiropractic specialists and the usefulness of combining chiropractic and epidural injection in particular cases of back pain. CLINICAL FEATURES: Two cases of low back pain, both with disk protrusions and osteophytic changes, had no response to several weeks of alternate day (or more) chiropractic care. A third case of herniated intervertebral disks and low back pain had no improvement from treatment with epidural steroidal injection. INTERVENTION AND OUTCOME: The two cases of failed response to chiropractic each experienced a dramatic therapeutic leap with a single treatment of manipulation under anesthesia/epidural steroid injection (MUA/ESI). Both patients maintained their improved condition on tapering schedules of maintenance chiropractic care. In the third case of failed response to ESI, severe pain precluded initial chiropractic treatment. This was only possible at the first treatment with MUA provided by epidural injection. A single treatment of MUA/ESI brought rapid and profound relief and was followed by continued chiropractic care. The patient remained pain-free except for a brief partial relapse that responded promptly to chiropractic. CONCLUSIONS: Cooperation between medical and chiropractic specialists is to be encouraged. These cases demonstrate cooperation between an anesthesiologist and a chiropractor. By using a single treatment of manipulation under epidural anesthesia/epidural steroid followed by continued chiropractic, we were able to lead our patients out of therapeutic dead ends and deal with the dilemma of a patient in too much pain to tolerate an initial chiropractic treatment. PMID- 7884332 TI - Chronic myelogenous leukemia in a 16-yr-old. AB - OBJECTIVE: To present an unusual case of chronic myelogenous leukemia (CML) in an adolescent with a complaint of leg pain. Clinical presentation is highlighted and a brief review of the childhood leukemias and common clinical features are outlined. CLINICAL FEATURES: A 16-yr-old black male was seen after suffering from leg and knee pains for 7 months. Exquisite tibial pain, normal radiographs and an abnormal CBC led to the diagnosis of leukemia. Subsequent referral for bone marrow examination confirmed the final diagnosis of chronic myelogenous leukemia. INTERVENTION AND OUTCOME: The patient was referred to a pediatric hematologist oncologist for medical management of his condition. He is currently receiving chemotherapy and the search for a suitable donor for bone marrow transplant is in progress. CONCLUSION: This case demonstrates the importance of considering one of the more common pediatric malignancies, such as leukemia, in the differential diagnosis of children with musculoskeletal complaints. Chronic myelogenous leukemia accounts for only 3-5% of cases of childhood onset. Its rare incidence in childhood constitutes the basis for this case report. PMID- 7884333 TI - A new management model for treating structural-based disorders: dental orthopedic and chiropractic co-treatment. PMID- 7884334 TI - Muscle testing response to provocative vertebral challenge and spinal manipulation: a randomized controlled trial of construct validity. PMID- 7884335 TI - Multicentric reticulohistiocytosis (lipoid dermatoarthritis) PMID- 7884336 TI - A comparative radiologic examination for unresponsive plantar fasciitis. PMID- 7884337 TI - A comparative radiologic examination for unresponsive plantar fasciitis. PMID- 7884338 TI - Absence of symmetry in superior articular facets on the first cervical vertebra in humans: implications for diagnosis and treatment. PMID- 7884339 TI - Research and Technology Transfer in Computerized Electrocardiography. Proceedings of the 19th annual ISCE conference. Santa Barbara, California, April 23-28, 1994. PMID- 7884340 TI - Effects of gender and age on heart rate variability in healthy individuals and in persons after sudden cardiac arrest. AB - The purpose of this study was to describe the effects of gender and age on heart rate variability (HRV) in healthy volunteers (n = 111; 40 men and 71 women) and in persons after sudden cardiac arrest (SCA) (n = 95; 79 men and 16 women). Frequency-domain measurements and six time-domain measurements of HRV (SDANN, 24 hour SD, SD, RMSSD, RR50, and %RR50) were taken. Two-factor analysis of variance was performed. In general, HRV was significantly lower in healthy women compared with healthy men in all the time-domain and frequency-domain variables except for the high-frequency components, RMSSD, RR50, and %RR50. There were no significant gender differences in the SCA sample. All the time-domain and frequency-domain measurements decreased with age in the healthy sample, but only the frequency domain measurements decreased with age in the SCA sample. PMID- 7884341 TI - Using directly acquired digital ECG data to optimize the diagnostic criteria for anterior myocardial infarction. AB - The use of a newly developed method of directly transferring digital data from Marquette electrocardiogram (ECG) systems (Milwaukee, Wisconsin) to personal computers for subsequent storage and analysis is illustrated. This method can eliminate the slowness and inaccuracy associated with measuring relevant ECG parameters from analog tracings and manually entering the data into a computer. In this study, the new method was used to derive ECG criteria for anterior myocardial infarction and to compare their performances to those of the current Marquette 12SL diagnostic program and of a group of cardiologists who had also interpreted the ECGs. Using angiographic data, 82 normal subjects and 55 patients with anterior myocardial infarction were identified. The digital ECG data from the patients in each group were transferred to a personal computer and frequency distributions of these data were generated. From these frequency distributions, the ECG criteria that most reliably separated the two groups were identified. The diagnostic performance of the best of these empirically derived criteria appears clinically superior to the performances of both the 12SL program and the cardiologists who had also interpreted the ECGs. PMID- 7884342 TI - Assessment of spatial and temporal characteristics of ventricular repolarization. AB - Measurement of dynamics and spatial characteristics of ventricular repolarization is of interest in assessing patients with ischemic heart disease, particularly in relation to the detection and characterization of ischemic events, identification of patients at risk of ventricular arrhythmias, or determination of the efficacy of drugs intended to alter repolarization. The QT interval (QTI) has been the index of choice for assessing repolarization abnormalities. It is a general measure of repolarization duration but lacks the power to assess the spatial aspects of repolarization and the ability to detect localized shortening in the setting of global prolongation. For direct cardiac surface measurement, QRST integrals and activation recovery intervals (ARIs) were used to assess repolarization and its disparity. The use of similar measurements from the body surface was proposed to provide better characterization of repolarization, its disparity, and its dynamics than is possible using the QTI. In one open-chest experiment using an intact canine heart and two experiments using isolated canine hearts suspended in a torso-shaped electrolytic tank, 64 epicardial electrograms and 192 torso surface electrocardiograms were measured simultaneously. Ventricular repolarization was globally altered by varying pacing cycle lengths or tank temperature. Atrial and ventricular pacing were used to assess sensitivity of repolarization indices to activation sequence. At the cardiac surface, (1) QTI tracks global repolarization changes but is affected by activation sequence and insensitive to localized shortening of repolarization; (2) distribution of QRST integrals reflects disparity of repolarization and is largely independent of activation sequence; and (3) ARI measures local repolarization duration and is only weakly affected by activation sequence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884343 TI - Atlas of paced body surface QRS integral maps for localization of the site of origin of postinfarction ventricular tachycardia. AB - Current mapping during radiofrequency (RF) catheter ablation of postinfarction ventricular tachycardia (VT) is based primarily on the use of single-site mapping techniques. Although such techniques are highly suitable for distinguishing the ultimate site where RF energy is delivered by enabling detailed localization of the exit site or critical component of the VT reentrant circuit, they are time consuming and inefficient for initial rapid identification of the arrhythmogenic target area. This study features the design and preliminary clinical application of a new noninvasive method that is aimed at speeding up the initial phase of the VT mapping procedure. This method is based on the use of an atlas of 62-lead body surface QRS integral map patterns that was previously developed using left ventricular pace mapping in patients with remote anterior or inferior myocardial infarction. The atlas contains 18 and 22 different paced QRS integral map patterns obtained in patients with previous anterior or inferior myocardial infarction, respectively. Each specific QRS pattern in the atlas provides a unique infarct-specific spatial electrocardiographic representation of the onset of ectopic ventricular activation in a circumscribed endocardial segment of the left ventricle. Localization of the segment of VT origin is obtained by visually or mathematically comparing the QRS integral map recorded during VT with one of the two sets of paced QRS integral maps contained within the atlas with the purpose of selecting the best matching paced QRS integral map pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884344 TI - QRST changes during and after percutaneous transluminal coronary angioplasty. AB - This study reports preliminary results on 45 patients who underwent percutaneous transluminal coronary angioplasty (PTCA); 120-lead data (including the 12-lead standard electrocardiogram [ECG]) were recorded before, during, and after balloon inflation. Twenty-one patients underwent PTCA for left anterior descending coronary disease, 13 for right coronary artery disease, and 10 for left circumflex; 1 patient had combined left anterior descending and right coronary artery disease. In each patient, voltage data recorded during the various phases of the procedure were compared with the patient's own baseline data. In 18 patients, 120 leads were also recorded 24 hours after PTCA. In this study, the usefulness of the standard 12-lead ECG was investigated in locating the coronary artery being occluded, in elucidating the mechanisms of the QRS changes, and in identifying changes occurring 24 hours after completion of the procedure. Results indicate that the observation of ST elevation in the 12-lead ECG may lead to ambiguous interpretation. Also, limiting observation to ST-T patterns alone instead of including QRS changes further hampers correct identification of the involved vessel. QRS modifications during inflation are interpreted as conduction disturbances, although other mechanisms are evoked: study of surface maps may contribute to the understanding of these mechanisms. Changes present 24 hours later are visible in the standard leads, but again, in the absence of the thoracic potential distribution, these are difficult to interpret. These changes were different from those observed after cessation of inflation at the end of the procedure. It is hypothesized that next-day changes may reflect reperfusion injury and/or represent myocardial stunning. Presence of injury and reversibility of changes require further investigation. Also, biochemical markers such as creatine kinase-MB mass, creatine kinase-MB activity, myoglobin, and troponin-T may help elucidate the significance of these findings. PMID- 7884345 TI - Discriminant function analysis of body surface potential maps in acute myocardial infarction. AB - Using a newly developed 64-electrode portable mapping device, QRS and ST-T isointegral maps were compared in 194 control subjects and 101 patients. One hundred ninety-four control subjects (mean age, 48 years; 120 men) with no history of cardiac disease were selected randomly and mapped. One hundred one patients (mean age, 62 years; 77 men) were mapped at presentation of chest pain suggestive of first myocardial infarction (MI); all patients had classic 12-lead electrocardiographic findings--46 with anterior and 55 with inferior MI. The diagnosis was confirmed in all cases by a significant rise in serial cardiac enzymes. The mean delay between onset of chest pain to map recording was 163 minutes. Of the 101 patients, 78 were first mapped outside the hospital. Applying discriminant function analysis to the isointegral measurements made on the control subjects and on the first map of MI patients achieved a correct classification of 97% of the control subjects (189 of 194) and 72% of the anterior (33 of 46) and 76% of the inferior (42 of 55) MI groups. This preliminary study suggests that discriminant function analysis, based on isointegral maps, not only provides a method of separating control subjects from MI patients but that it can also differentiate between types of infarct. Further studies are required to improve the predictive values of discriminant function and to extend the methodology to assess both the site and size of MI. PMID- 7884346 TI - Interventional electrophysiology. State-of-the-art and future directions. PMID- 7884347 TI - Radionuclide imaging tools for understanding arrhythmia mechanisms. PMID- 7884348 TI - Considerations in the design and implementation of computerized EP laboratory systems. PMID- 7884349 TI - Functional approach to site-by-site catheter mapping of ventricular reentry circuits in chronic infarctions. PMID- 7884350 TI - Three-dimensional endocardial mapping system using a novel x-ray imager and locating catheter. AB - Percutaneous radiofrequency catheter ablation (RFCA) has a very high success rate for certain arrhythmias, such as Wolff-Parkinson-White syndrome and idiopathic ventricular tachycardias in the right ventricular outflow tract. These arrhythmias are typically characterized by a single site of arrhythmogenic tissue that is well bounded by anatomic markers. Success rates for RFCA for reentrant ventricular tachycardias, tachycardias not closely associated with anatomic markers, and those having larger tissue areas requiring multiple overlapping lesions have been significantly lower. An endocardial mapping system is being developed that includes a fluoroscopic imager that scans the field of view with a series of small x-ray beams and electrophysiology catheters modified to include miniature x-ray sensor elements. Preliminary work indicates that the accuracy of determining the mapping catheter location relative to the reference catheters will be +/- 1.5 mm. Substituting a highly accurate three-dimensional coordinate system for anatomic markers could improve the success rate of RFCA for complex arrhythmias. PMID- 7884352 TI - Simulation of intracardiac electrograms with a moving dipole source. Role of electrode geometry and high-pass filtering. PMID- 7884351 TI - Effects of age, sex, and race on ECG interval measurements. AB - The effects of age, sex, and race on the electrocardiogram (ECG) were studied using three separate populations: a pediatric group of 1,782 neonates, infants, and children, and adult white group of 1,555 individuals, and an adult Chinese cohort of 503 individuals. All ECGs were processed using the same computer program, and various interval measurements were derived, including QRS duration, heart rate, QT dispersion, and selected Q-wave durations. Also, a small subgroup of 195 white subjects had a signal-averaged ECG recorded. In the pediatric group, there was a clear link between age and QRS duration, which increased linearly from about 1 year of age to adolescence. In the adults, the principal differences were an increased QRS duration in men compared with women both in the standard and signal-averaged ECG. Upper limits of normal heart rate also tended to be higher in women than in men in the two adult populations. Small racial differences could be seen in some measurements, but were not thought to be of clinical significance. PMID- 7884353 TI - Automated analysis of spontaneously occurring arrhythmias by implantable devices. Limitations of using rate and timing features alone. AB - Real-time automated systems for arrhythmia analysis by implantable antitachycardia devices have been designed to incorporate two-channel rate criteria with intracavitary atrial and ventricular electrogram morphology. Because the power requirements for morphologic analysis substantially limit antitachycardia device longevity, the authors sought to develop an alternative algorithm that relies solely on rate and three newly developed timing features: onset (median ventricular rate filtering to detect abrupt onset), loss of atrioventricular (AV) sequency (premature ventricular depolarizations), and regularity-multiplicity (minimal median cycle length variation concurrent with integral [n:1] AV periodicity). This system was assessed using spontaneously occurring arrhythmias in patients undergoing electrophysiology studies. Electrograms were captured on FM tape (1-500 Hz) using biopolar catheters in the high right atrium and the left ventricular apex. In 11 patients, 25 distinct arrhythmias were analyzed, which included sinus tachycardia (ST) (1 passage), supraventricular tachycardia (SVT) (6 passages), ventricular tachycardia (VT) with concurrent sinus rhythm (16 passages), VT with concurrent atrial flutter (VT/AFl) (2 passages), and ventricular fibrillation (VF) (1 passage). The algorithm correctly diagnosed 1 of 1 episode of ST, 4 of 6 episodes of SVT, 15 of 16 episodes of VT with concurrent sinus rhythm, 0 of 2 episodes of VT/AFl, and 1 of 1 episode of VF. Ventricular tachycardia episodes were misdiagnosed as SVT because of absence of loss of AV sequency in VT onset (1 episode), presence of multiplicity between VT and AFl (1 episode), and absence of VT regularity during AFl (1 episode).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884354 TI - Development of ECG criteria to diagnose the number of narrowed coronary arteries in rest angina using new self-learning techniques. AB - Recently, an evaluation of the value of the resulting electrocardiogram recorded during chest pain for identifying high-risk patients with three-vessel or left main stem coronary artery disease has resulted in the definition of one characteristic pattern: ST-segment depression in leads I, II, and V4-V6 and elevation in lead aVR. This study evaluated the generation of such criteria using two self-learning techniques: neural networks and induction algorithms. In 113 patients, five variables, including the amount of ST elevation, the number of leads with abnormal ST-segments, and this above-mentioned characteristic sign, were correlated with the number of narrowed vessels. All patients were randomly subdivided into a training (n = 63) and test set (n = 50), stratified for both this characteristic sign and for the vessel involved. Using the learning set, the neural network and the induction algorithm were trained separately to identify (1) pure left main stem disease and (2) three-vessel disease and left main stem disease. The neural network was trained for 1,000 runs. The induction algorithm was trained, allowing all variables to be used in any order. The experiments were repeated after adding weight factors to promote the recognition of the more severe cases. Subsequently, the ST elevation in all 12 leads was added to the training and test sets, once with and once without the polarity of the ST deviation. Altogether, 18 different combinations were evaluated. Basically, the neural network and the induction algorithm approach misclassified the same cases in corresponding test combinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884355 TI - Validity of the uniform double layer in the solution of the ECG forward problem. AB - This study attempted to solve the electrocardiographic forward problem (ie, to predict body surface potential fields from pathways of depolarization). A perfused heart was suspended in a cylinder and surrounded with fluid of the conductivity of the lung. Computation of potential fields included conductivity and boundary effects and assumed a uniform double-layer source. Three instants (early, late, and mid QRS) during normal depolarization and one instant during a stimulated beat were studied. There was good qualitative agreement between recorded and predicted fields early and late in the QRS and during the stimulated beat, but there were quantitative differences. The cardiac generator was far stronger late in the QRS. In mid QRS, the agreement between recorded and predicted fields was very poor. To resolve questions raised in this study, potentials around a small volume of stimulated tissue were recorded and predicted. Recorded potentials were compared with potentials calculated (1) on the assumption that the cardiac generator is a uniform double layer and (2) on the assumption that all current flows along the long axes of the cardiac fibers. The recorded potentials compared most favorably with the second of these. These studies led to the opinion that the uniform double-layer assumption is inadequate for prediction of body surface potential fields from depolarization pathways. Other studies of the forward and inverse problem that assume a uniform double layer source are considered to be successful and therefore disagree with this study's conclusion. It appears that the question needs further experimental study. PMID- 7884356 TI - Effects of coupling heterogeneity on fractionated electrograms in a model of nonuniformly anisotropic ventricular myocardium. AB - To further understand the relation between heterogeneously infarcted myocardium and fractionated electrograms, a computer model was used to test the hypothesis that the way electrogram metrics change with electrode location relates to statistical properties of the underlying myocardium. A sheet of Beeler-Reuter elements was coupled with cytoplasmic resistance to form cells. Junctional resistance values were assigned using a recursive randomization to produce a fractal pattern, simulating damage from disrupted blood supply. The pattern's correlation dimension, D, was a statistical measure of heterogeneity. Unipolar electrogram's amplitude, duration, number of inflections, peak frequency, bandwidth, and the rate of change of metrics with height were calculated. Analysis of variance indicated (P < .0001) that peak-to-peak amplitude and bandwidth decreased at a slower rate when height was increased above heterogeneous tissue as compared with homogeneous tissue. These findings could be useful during clinical mapping procedures as statistical estimates of tissue structure. PMID- 7884357 TI - Impaired heart rate variability and increased ventricular ectopic activity in patients with left ventricular hypertrophy. PMID- 7884358 TI - Smoothing techniques for improving the repeatability of the automated diagnosis of inferior myocardial infarction. AB - This study describes the implementation of novel techniques that have been designed with the aim of improving the repeatability of the diagnostic section of the Glasgow electrocardiographic (ECG) analysis program. Specific reference is made to the agreement in consecutive computer-assisted diagnoses of inferior myocardial infarction (IMI). Inherent repeat variation was estimated in ECG parameters of interest and used in conjunction with smoothing methods to produce a continuous Q-wave index ranging from 0 (no IMI) to 1 (IMI). A decision as to the presence or absence of IMI was then made on the basis of this smooth index. The sensitivity and specificity of the new approach remain unchanged from the conventional procedure when analyzing single ECGs. However, consistency in interpretation of day-to-day and minute-to-minute ECG interpretations was enhanced. Specific reference is made to the agreement between consecutive pairs of computer-assisted diagnoses of ECGs from the same patient with which one or both interpretations was that of IMI. PMID- 7884359 TI - Use of artificial neural networks within deterministic logic for the computer ECG diagnosis of inferior myocardial infarction. AB - An investigation into the use of software-based artificial neural networks for the electrocardiographic (ECG) detection of inferior myocardial infarction was made. A total of 592 clinically validated subjects, including 208 with inferior myocardial infarction, 300 normal subjects, and 84 left ventricular hypertrophy cases, were used in this study. A total of 200 ECGs (100 from patients with inferior myocardial infarction and 100 from normal subjects) were fed to 66 supervised feedforward neural networks for training using a back-propagation algorithm. QRS and ST-T wave measurements were used as the input parameters for the neural networks. The best performing network using QRS measurements only and the best using QRS and ST-T data were selected by assessing a test set of 292 ECGs (108 from patients with inferior myocardial infarction, 84 from patients with left ventricular hypertrophy, and 100 from normal subjects). These two networks were then implanted separately into the deterministic Glasgow program for further study. After the implementation, it was found necessary to include a small inferior Q criterion to improve the specificity of reporting inferior myocardial infarction, thereby producing a small loss of sensitivity as compared with use of the network alone. The use of an artificial neural network within the deterministic logic performed better than either alone in the diagnosis of inferior myocardial infarction, producing a 20% gain in sensitivity with 2% loss in overall specificity compared with the original deterministic logic. PMID- 7884360 TI - Time-domain and frequency-domain analyses of the signal-averaged ECG in patients with sustained ventricular tachyarrhythmia and nonischemic heart diseases. AB - Signal-averaged electrocardiogram (ECG) variables were analyzed in 81 patients with ventricular tachyarrhythmia and nonischemic heart disease using the ART LVP 101 EPX system (Austin, TX): 15 ventricular tachycardia patients with arrhythmogenic right ventricular dysplasia (ARVD), 7 ventricular tachycardia patients with dilated cardiomyopathy, 25 patients with "idiopathic" verapamil sensitive left ventricular tachycardia, 24 patients with "idiopathic" right ventricular tachycardia, and 10 "idiopathic" ventricular fibrillation (IVF) patients with rbbb pattern and ST-segment elevation in the precordial leads. Data from 52 normal control subjects were also analyzed. The first study was to test the hypothesis of any difference in signal-averaged ECG indices between patients with ARVD and patients with dilated cardiomyopathy. Longer filtered QRS duration and T40 and higher amplitude of the terminal filtered QRS complex outside the end of the standard QRS complex (log V-outside) were noted in patients with ARVD (filtered QRS duration, 172 vs 144 ms, P < .05; T40, 94 vs 62 ms, P < .05; log V outside, 1.48 vs 0.56, P < .01). Endocardial mapping showed noticeable extension of fractionated electrograms in the right ventricle and longer duration of fractionated intracardiac electrograms in patients with ARVD, which might explain the difference in signal-averaged ECG indices between these two diseases. The second study was to test the hypothesis of and the variables that can suggest the arrhythmogenic substrate in patients with idiopathic ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884361 TI - Ethnic differences in ECG amplitudes in North American white, black, and Hispanic men and women. Effect of obesity and age. AB - General trends were investigated in the age-evolution of electrocardiogram (ECG) patterns using ECG data of North American white, black, and Hispanic men and women aged 25-74 years, derived from the Second National Health and Nutrition Examination Survey and the Hispanic Health and Nutrition Examination Survey. The data were stratified by race, sex, age, and obesity. There were substantial racial differences in ECG amplitudes. In general, ECG amplitudes and amplitude combinations used in left ventricular hypertrophy (LVH) criteria were larger in blacks than in whites. RV5 was smaller in all age groups of Hispanic women and in younger men, and RaVL was larger in Hispanics than in whites. There was, however, no significant difference in RaVL + SV3 amplitude between Hispanics and whites except in the youngest age group. The QRS frontal plane axis increased in men and women in all three racial groups by about 8 degrees per decade of age. Overweight was associated with 14 degrees more horizontal axis. RaVL and RaVL + SV3 amplitudes increased systematically with age and overweight, but there was an opposite tendency in RV5 amplitude. Multivariate logistic regression analyses indicated that age and the QRS axis had a relatively minor influence on LVH likelihood. Being black was associated with a more than fourfold excess of LVH by the Minnesota code criteria and a nearly threefold excess of LVH by the Cornell voltage criteria. Being overweight did not influence the odds ratio for LVH by the Cornell voltage criteria except in Hispanics, but the odds ratio for LVH was reduced by about 25% according to the Minnesota code criteria. The odds ratio of having LVH differed substantially for men and women by the Minnesota code and Cornell voltage criteria. Whereas there was a more than twofold excess likelihood of LVH in men by the Minnesota code criteria, there was a more than threefold excess of LVH likelihood in women by the Cornell voltage criteria when age, obesity, QRS axis, and race were simultaneously included as covariates in the logistic regression model. PMID- 7884362 TI - Combined time-domain and spectral turbulence analysis of the signal-averaged ECG improves its predictive accuracy in postinfarction patients. AB - The predictive accuracy of time-domain (TD) late potential analysis of the signal averaged electrocardiogram in postmyocardial infarction (MI) is limited by the high incidence of false positives in inferior MI. However, frequency-domain spectral turbulence (ST) analysis suffers from a high incidence of false positives, especially in anterior MI. A prospective study was conducted of 262 patients with acute MI to investigate the hypothesis that combined TD and ST analyses of the signal-averaged electrocardiogram could improve its predictive accuracy for serious arrhythmic events in the post-MI period. Abnormal TD criteria were RMS40 less than 25 microV at 25 Hz plus RMS40 less than 16 microV at 40 Hz, and abnormal ST criteria were a turbulence score of 3 or 4. Seventeen patients had arrhythmic events during 10.5 +/- 2.4 months of follow-up evaluation (13 sudden cardiac death judged to be due to arrhythmia and 4 nonfatal sustained ventricular tachycardia). The total predictive accuracy of combined TD and ST (92%) was higher than TD (87%), whereas ST had the lowest total predictive accuracy of 78%. The negative predictive accuracy of all three analyses was high (96-97%). However, the positive predictive accuracy of TD (28%) was higher than ST (14%). Combined TD and ST significantly improved the positive predictive accuracy of the test to 35% in the total group and to 40% in patients with first anterior or inferior MI. The best results were obtained in patients with first anterior MI, where the positive predictive accuracy of combined analysis was 50%. PMID- 7884363 TI - Time-frequency structure of the high-resolution ECG. AB - This study considers the problem of representing high-resolution ECG (HRECG) signals in the time-frequency plane using spectrotemporal mapping (STM). High resolution ECG signal components overlap in both time and frequency. The central issue with STM techniques is whether sufficient time-frequency resolution exists to discriminate normal and abnormal QRS signals. The trade-off between signal resolution in time and in frequency must be made without a priori knowledge of the HRECG's time-frequency structure. A simulation experiment was performed to examine the time-frequency distribution of normal, abnormal low-level (late potentials), and bundle branch block components of the QRS. Results suggest that discrimination of these signals with STM is problematic. Signals and noise within the HRECG ensemble can, however, be easily distinguished. This observation forms the basis of a new optimally filtered ensemble averaging technique for signal-to noise ratio enhancement. PMID- 7884364 TI - Time-domain and frequency-domain analyses of the signal-averaged ECG in patients with ventricular tachycardia and ischemic versus nonischemic dilated cardiomyopathy. AB - The value of time-domain and frequency-domain (spectral turbulence) analyses of the signal-averaged electrocardiogram was investigated to predict induced sustained monomorphic ventricular tachycardia (VT). Two groups of patients with spontaneous nonsustained VT and left ventricular ejection fraction less than 50% were enrolled: 70 patients with idiopathic dilated cardiomyopathy (group 1) and 70 patients with ischemic heart disease (group 2). Sustained VT was induced in 9 cases (13%) in group 1 and 16 (23%) in group 2. The prevalence of abnormal time domain and spectral turbulence analysis was 16 and 37%, respectively, in group 1 and 27 and 51%, respectively, in group 2 (NS). In group 1, the predictive accuracy of time-domain and spectral turbulence analysis for induced VT was 86 and 67%, respectively (P < .01). In group 2, the predictive accuracy of the two techniques for induced VT was, respectively, 79 and 66% (NS). In both groups, the predictive accuracy of time-domain analysis was higher than that of spectral turbulence analysis in patients with intraventricular conduction defect (IVCD): 65 versus 25%, respectively, in group 1 (P < .01), and 81 versus 44%, respectively, in group 2 (P < .05). However, the predictive accuracy of time domain and spectral analyses was similar in patients without IVCD: 94 versus 84%, respectively, in group 1, and 77 versus 74%, respectively, in group 2. Thus, in patients with dilated cardiomyopathy, (1) the etiology does not affect the predictive accuracy of time and frequency domain and frequency-domain analyses have high predictive accuracy in patients without IVCD; and (3) spectral turbulence analysis does not improve VT prediction in patients with IVCD. PMID- 7884365 TI - Spectral analysis of the cardiac cycle of signal-averaged Frank leads from patients with ventricular tachycardia. AB - Identification of the spectral features in electrocardiograms that distinguish patients prone to ventricular tachycardia (VT) is a prerequisite to increasing the diagnostic power of the signal-averaged electrocardiogram (SAECG). To determine distinguishing features of the magnitude spectrum, the spectra of SAECGs of sinus beats were analyzed over the entire cardiac cycle from 32 patients with VT, 30 without VT, and 10 normal control subjects. The magnitude spectra of the Frank SAECGs separated patients with VT from those without VT over the band from 7 to 140 Hz with a P value of .000000047. To determine distinguishing features of phase and group-delay spectra, SAECGs of sinus beats over the entire cardiac cycle were analyzed from 57 patients with VT, 65 without VT, and 20 normal control subjects. Unwrapped phase spectra from SAECGs of the entire cardiac cycle were calculated with respect to the onset of the Q wave. Phase spectra of SAECGs from patients with VT differed from those from non-VT patients at frequencies of 60 Hz or greater (P = .00085). Average group delays in SAECGs from patients with and without VT differed (P = .00000069) from 14 to 24 Hz. Group delays in the VT patients in the 14-24-Hz band were on average 9 ms and 5 ms longer than those of the non-VTs and normal subjects, respectively. Time domain reconstructions demonstrated that distinguishing frequency bands were detectable throughout the QRS complex, ST-segment, and T wave in SAECGs from each group. Thus, the spectra of SAECGs over the cardiac cycle contain features that together with temporal features from throughout the cardiac cycle are essential in improving methods for stratifying risk of VT. PMID- 7884366 TI - Spectral turbulence analysis versus time-domain analysis of the signal-averaged ECG in survivors of acute myocardial infarction. AB - This study compared the time-domain and spectral turbulence analyses of signal averaged electrocardiogram (ECG) for the prediction of risk after acute myocardial infarction. Signal-averaged ECGs were recorded in 553 survivors of acute myocardial infarction before hospital discharge. The study excluded cases with bundle branch block and other conduction abnormalities, and patients were followed for at least 1 year. During the first year of the follow-up period, 30 patients died and 20 presented with ventricular tachycardia/fibrillation. The signal-averaged ECG recordings were analyzed using conventional time domain at 40 250 Hz and spectral turbulence analyses. The indices provided by both types of analysis were compared in patients with and without endpoints. The optimum positive predictive characteristics were calculated for the prediction of all cause mortality and of ventricular tachycardia based on the time domain and on the spectral turbulence indices. Spectral turbulence analysis provided significantly lower positive predictive accuracy (14.5% at 40% sensitivity) than the time-domain analysis (26.7% at 40% sensitivity) for prediction of ventricular tachycardia/fibrillation during 1 year after infarction (P < .01). However, spectral turbulence analysis provided significantly higher positive predictive accuracy (27.2% at 30% sensitivity) than the time-domain analysis (16.9% at 30% sensitivity) for the prediction of 1-year all-cause mortality (P < .01). Thus, spectral turbulence analysis was inferior to the time-domain analysis in predicting ventricular tachycardia/fibrillation during the first year after myocardial infarction, but it was more powerful in predicting 1-year mortality. PMID- 7884367 TI - From signal/noise to information content/noise. Reconsidering the statistical analysis of continuous ST-segment data streams with gaps: potential optimization of application-specific information content using left, right, and interval censoring. PMID- 7884370 TI - Derived 12-lead ECG. Comparison with the standard ECG during myocardial ischemia and its potential application for continuous ST-segment monitoring. PMID- 7884368 TI - Implementation of ST-segment criteria in clinical monitoring devices. Implications of criteria from field trials and the federal regulatory process. AB - Manufacturers are challenged with providing ST-segment monitoring devices in a timely manner that meet the needs of clinicians and that satisfy the purview of the Federal Drug Administration (FDA) Office of Device Evaluation. The initial challenge is to explain the intended use for the product; are clinicians using the monitoring device to view measured ST-segment values or are they attempting to detect ischemic changes? A device that has only been tested by the manufacturer for its accuracy in detecting ST level changes may only be used for that purpose. A "field trial" of several months at clinical sites is typically conducted to confirm the accuracy of the St-segment measurement and to validate the device's "ease of use." If the monitoring device is intended for detecting ischemic changes, it must be clinically tested to demonstrate this capability. A "clinical trial" to detect ischemic changes could start to approach the scope and time one might expect for the clinical testing of a drug. Alarming for an ST segment level change provides a dilemma for manufacturers. The FDA has questioned the rationale for providing ST alarms. The question comes from the position that ST-segment level changes have a low positive predictive accuracy for detecting "ischemia" (implications: clinical trial, etc.) and that many ST-segment level changes are not clinically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884369 TI - Basic components and patterns of acute ischemia recovery assessed from continuous ST monitoring in acute myocardial infarction treated by thrombolytic therapy. AB - Continuous ST monitoring of the lead showing the highest ST elevation on the admission 12-lead electrocardiogram was performed in patients with acute myocardial infarction of 6 hours or less enrolled in the OSIRIS and GUSTO trials. ST elevation measured at j + 50 ms was averaged from all normal beats every 20 seconds. ST trends were visually analyzed by two observers blinded from the thrombolytic treatment, its onset, and coronary angiograms performed 21 hours (median) after thrombolysis. Three basic and consecutive components were considered for analysis: the initial amplitude of ST elevation (A1), the maximal amplitude recovery (REC), and the minimal ST amplitude (A2). Prespecified patterns (PAT) were considered: PAT 1 integrated permanent A1 elevation followed by REC, PAT 2 intermittent A1 elevation, and REC. Prespecified pattern 3 was considered in absence of REC. Twenty-four-hour trends were recorded in 347 patients and judged adequate in 306 (88%) followed by angiography in 268 (77%). This group was not clinically different from the 79 patients without ST/angiography. Prespecified pattern 1 was identified in 81%, PAT 2 in 8%, and PAT 3 in 11% of the patients. The positive predictive value of PAT 1 + 2 for coronary patency was 94%, the negative predictive value 72%, sensitivity 96%, and specificity 60%. A salient feature was the occurrence of ST overshoot defined by a > or = 1 mm increase above A1 within the first minutes of REC. Overshoot occurred in 35% of PAT 1 and predicted subsequent patency in all but two patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884371 TI - Reassessing the clinical significance of ST-segment depression that occurs concomitantly with the ST-segment elevation during acute myocardial infarction with the use of continuous ST-segment analysis. PMID- 7884372 TI - Reflections on the 1993 ISCE meeting and progress report with future directions. PMID- 7884373 TI - ECG myocardial infarct size: a gender-, age-, race-insensitive 12-segment multiple regression model. I: Retrospective learning set of 100 pathoanatomic infarcts and 229 normal control subjects. AB - In this early study of ongoing work with multiple regression modeling for mapping myocardial infarct (MI) into 12 left ventricular (LV) segments, promising results have been presented using electrocardiographic (ECG) QRS variables that are gender, age, and race insensitive (GARI), the GARI-QRS 12-segment multiple regression model. These include Q, R, and S duration, expressed as percentage total QRS duration, and R/Q duration, R/Q amplitude, R/S duration, and R/S amplitude variables. For version I, building 12 regression models using 68 single and 32 multiple MIs, the GARI-QRS variables correlated with pathoanatomic MI in each of 12 segments with r values ranging from .67 to .88. In version II of the model, using all MIs and 229 normal subjects, r = .73-.91. Version II predictions of MI in 12 LV segments for each subject were used to calculate the predicted total percentage LV infarct, which correlated well with that found at autopsy. The r values found were .81 for all single MIs, .73 for multiple MIs, and .80 for all MIs taken together. With refinements of the input ECG variables to include (1) improvement in the GARI-QRS variables, (2) adding a significant number of subjects with hypertrophies and conduction defects with and without MI to an expanded learning set, and (3) applying the enhanced 12-LV-segment regression models to a similar test set, it is to be expected that these regression models can be improved even further in such a way as to be applicable to general clinical populations using routine computerized ECG analysis programs. PMID- 7884375 TI - Parameter evaluation of the inverse power-law spectrum of heart rate. A quantitative approach for ECG arrhythmia analysis. AB - A preliminary study was performed to ensure reliable R-wave detection and fiducial mark location. A generalized phase-sampling model for spectral estimation was then used, based on an interest in beat-to-beat variations. Heart rate spectrum characteristics of 32 presumed-normal subjects and 44 records from the MIT-BIH electrocardiographic database (Massachusetts Institute of Technology, Cambridge, MA) were analyzed and three parameters were calculated: regression line slope, intercept, and cross correlation between the spectral data and the regression lines. Evaluation of these inverse power-law spectrum parameters provides a potential quantitative approach for characterizing erratic fluctuations of heart rate and is possibly used to distinguish between healthy and abnormal subjects. From the 44 recordings in the MIT-BIH database, a V-shaped curve was found in a plot of the regression line slope versus cross correlation. The results for both unmedicated and medicated patients with normal sinus rhythm cluster in the top left region of the graph. Also, 29 of the presumed-normal subjects cluster in the same region. Patients with premature ventricular contraction beats cluster in the top right region of the V-shaped curve. The rest of the recordings from the variety of arrhythmia cases in the database have low slopes and cross correlations, so they cluster near the apex of the V-shaped curve. Three volunteers who each had more than 32 atrial premature contraction and premature ventricular contraction beats also fall in this region of the graph. The results from 10 young volunteers from the United States and 15 volunteers from seven other countries cluster into different regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884374 TI - ECG changes during myocardial ischemia. Differences between men and women. AB - Women have a higher short-term mortality in acute myocardial infarction (MI) compared with men. This may be partly explained by differences in risk factors such as age and diabetes. However, several reports have focused on the occurrence of a sex bias making women less likely to be subjected to angiography and revascularization as well as aggressive pharmacologic treatment of acute MI. The decision to initiate these procedures is often based on ischemic changes of the electrocardiogram. It was therefore investigated whether differences between men and women in magnitude of electrocardiographic changes during myocardial ischemia could explain some of the differences previously reported. A total of 178 patients with chest pain suggestive of MI (135 men and 43 women) included in a study of thrombolytics were monitored for 24 hours with continuous vectorcardiography. Also, 81 patients with stable angina pectoris undergoing elective angioplasty were monitored during the procedure. In patients admitted with suspicion of MI, the initial summated ST deviation was 178 +/- 146 microV for men as compared with 105 +/- 91 microV for women (P = .002). During angioplasty, men had significantly more pronounced maximum ST deviation during inflation of the balloon (235 +/- 165 vs 156 +/- 89 microV; P = .036). In conclusion, men have more pronounced ST changes than women during myocardial ischemia. When fixed magnitudes of ST deviation are required for initiating therapy such as thrombolytics, this will favor treatment of men. A sex-adjusted limit for administrating thrombolytic drugs may be warranted in the light of the above findings. PMID- 7884376 TI - Nycthemeral profile of nonspectral heart rate variability measures in women and men. Description of a normal sample and two sudden cardiac arrest subsamples. AB - Heart rate variability (HRV), a noninvasive systemic index of the central autonomic nervous system, demonstrates considerable within-subject variability, including a strong systematic 24-hour nycthemeral (or less precisely, circadian) component. Recent interest in the timing of sudden cardiac arrest (SCA), especially the pronounced morning rise in sudden deaths, has motivated research into coincident dynamic phenomena in HRV indices of central autonomic nervous system activity. In this study, statistical (nonspectral) HRV measures (SD and %RR50) were summarized for consecutive 15-minute blocks from 24-hour Holter electrocardiogram tapes. Six subgroups were scrutinized: women and men respectively in three clinical strata (normal subjects [n = 85 women and 40 men], SCA with no current or prior myocardial infarction [MI] [n = 9 women and 31 men], SCA with old MI [n = 7 women and 48 men]). Significant nycthemeral effects were observable for all HRV measures in five of the six groups, with a dramatic fall in HRV during the hours of the morning with the highest phenomenologic incidence of SCA. Both strata of SCA subjects had much lower HRV than the normal subjects. This effect was strongest during the night-time hours, particularly for a purported index of vagal tone (%RR50). For reasons that are not known, the nine female SCA survivors who had no current or previous MI presented very distinct 24 hour patterns for the HRV measures studied. Twenty-four-hour profiles of short term statistical HRV provide a rich field for the observation of within-subject adaptations of the central autonomic nervous system inputs to the heart in both normal and clinical subgroups. PMID- 7884377 TI - Clinical relevance of assessing QT dynamicity in Holter recordings. AB - Ventricular repolarization (VR) duration is an electrophysiologic parameter that is poorly explored in the conventional electrocardiogram. The heart rate (HR) and the autonomic nervous system (ANS) condition its variations. The static QT measurement in the surface electrocardiogram and its correction using the Bazett formula constitute inadequate tools. The three-dimensional Holter recordings and their computerized analysis are better adapted to assess the dynamicity of VR, a relevant image of the myocardial state. QT and RR values are linearly correlated over 24 hours, but this does not allow one to study specifically the respective roles of HR and ANS on repolarization changes. To do so, it is necessary to select appropriately the QRST complexes according to their environment: not only the last RR cycle but the mean HR over the preceding minutes, and the circadian influences must be controlled to differentiate the role of the short- and long term influences. Combining the ATREC and the CAVIAR softwares now permits control of both time and space dimensions and to measurement of the QT variations with a precision of the order of 1 ms, a performance necessary to assess tiny but meaningful changes. The QT interval is shorter, and the slope of the QT/RR regression line is steeper at daytime compared with night, and many situations modify this normal behavior. Aging lengthens the QT interval and reduces the day to-night differences of QT duration and dynamicity. In contrast with duration, dynamicity does not depend on gender. Any heart disease, left ventricular hypertrophy, or heart failure alter QT dynamicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884378 TI - Automatic detection of spatial and dynamic heterogeneity of repolarization. AB - Heterogeneity of ventricular repolarization is associated with the development of life-threatening ventricular arrhythmias. Temporal heterogeneity of repolarization may be manifest in an individual beat (spatial heterogeneity) or in a sequence of beats (dynamic heterogeneity). Spatial inhomogeneity of repolarization throughout the myocardium may be expressed electrocardiographically as dispersion of repolarization durations computed in simultaneously recorded leads. The beat-to-beat changes in the repolarization pattern (duration and/or amplitude) may account for a dynamic (time-dependent) dimension of heterogeneity, occasionally seen as T-wave alternans. A visual detection of heterogeneous repolarization is a time-consuming, observer dependent, and frequently inaccurate process. Therefore, we developed computer algorithms designed to detect automatically (1) dispersion of repolarization and (2) nonvisible T-wave alternans from digitally recorded (1,000 Hz) X, Y, and Z electrocardiogram leads. This automatic approach was subsequently tested in 10 patients with idiopathic long QT syndrome and in 10 age-matched normal subjects. Long QT syndrome patients presented with significantly higher indices of heterogeneity in comparison with the control subjects; the dispersion of repolarization was 44 +/- 11 and 13 +/- 6 ms, respectively (P < .01), and T-wave alternans index was 0.40 +/- 0.37 and 0.03 +/- 0.06, respectively (P < .01). Simultaneous evaluation of spatial (dispersion of repolarization) and dynamic (T wave alternans) aspects of repolarization provides new insight into heterogeneity of electrical recovery after myocardial depolarization. The automatic detection of repolarization dispersion and T-wave alternans in digital electrocardiogram recordings provides a practical method to evaluate heterogeneity of repolarization and may be useful for stratifying patients at risk of ventricular arrhythmias. PMID- 7884379 TI - Sex differences in the rate of cardiac repolarization. PMID- 7884380 TI - Implantable monitoring systems. Design considerations and challenges. PMID- 7884381 TI - Sensitivity and specificity of a dual-chamber arrhythmia recognition algorithm for implantable devices. AB - Present ventricular rate-based arrhythmia detection algorithms lack specificity. Using a training set of 109 endocardial electrogram recordings, a sensitive and specific dual-chamber arrhythmia recognition algorithm has been developed. The algorithm uses atrial and ventricular rates, irregularity, degree of beat-to-beat similarity, and measure of electrogram complex distinctiveness to arrive at a diagnostic conclusion. A test set of 121 endocardial electrogram recordings obtained during provocative electrophysiology studies was then used for blinded validation of the algorithm. In normal rhythm, 1:1 tachycardia, atrial tachycardia, atrial flutter, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation, the percentages of sensitivity/specificity were, respectively, 100/99, 100/99, 80/99, 89/98, 91/97, 92/100, and 100/98. Although ventricular rate alone can usually distinguish normal rhythm, ventricular tachycardia, and ventricular fibrillation, it is confounded by atrial arrhythmias and 1:1 tachycardias. When tested on a database, a ventricular rate-only algorithm resulted in sensitivity/specificity of 100/65, 90/78, and 100/99%, respectively, for these three rhythms. Therefore, the dual-chamber algorithm based on both temporal and morphologic measures provides better distinction of normal rhythm and ventricular tachycardia than existing methods, without sacrificing sensitivity. PMID- 7884382 TI - Model-based analysis of the ECG during early stages of ventricular fibrillation. AB - During the early stages of ventricular fibrillation (VF), identification of the changes in electrocardiographic (ECG) characteristics may be helpful in the determination of defibrillation energy for implantable defibrillators. The hypothesis that the ECG can be quantified by using autoregressive (AR) modeling during VF was tested. Electrocardiograms were recorded for durations of up to 60 seconds of VF in five isolated rabbit hearts. Fourth-order AR parameters of successive 2-second epochs with 50% overlapping of data segments were estimated. At the beginning of VF, mean values of frequency of the first and second poles were 12.5 +/- 1.2 Hz and 24.7 +/- 1.9 Hz, respectively. During VF, frequencies of these poles decreased. At the end of 60 seconds, pole frequencies were 8.7 +/- 1.1 Hz and 21.4 +/- 0.8 Hz. Intersubject variability of the frequencies of the poles was found to be low. Maximum standard deviations for the frequencies of the first and second poles were determined to be 1.9 and 2, respectively. Results of this study show that the VF ECG can be modeled by using the AR modeling technique, and it is possible to quantify the changes in the frequency content of the ECG during VF by using this modeling method. PMID- 7884383 TI - Analysis of PTCA-induced ischemia using an ECG inverse solution or the wavelet transform. AB - In patients without significant collaterals, percutaneous transluminal coronary angioplasty (PTCA) produces acute transient ischemia that is detectable in both standard electrocardiograms (ECG) and body surface potential maps (BSPMs). Control recordings made before or between inflations provide personalized baselines, which isolate the effects of ischemia from interpatient differences, such as torso shape and electrode location. In this study, two methods of evaluating PTCA-induced ischemia from BSPM recordings are presented. In the first method, an ECG inverse solution that estimates epicardial potentials from body surface signals using a realistic model of torso geometry is applied. The strength of this method lies in its potential ability to localize areas of cardiac ischemia on the epicardial surface. In the second approach, wavelet transforms were used to perform a multiresolution decomposition of the BSPM data into different frequency bands. The basis functions of the wavelet transform are time-limited and narrow band and hence can be expected to be sensitive to features of the BSPM that originate in discrete electrophysiologic events, such as intrusion of the activation front onto regions of ischemia or arrhythmias due to local conduction abnormalities. The method also offers a means of temporal and frequency localization of cardiac events related to the initiation of injury currents and abnormal conduction due to PTCA-induced ischemia. The inverse solution and the wavelet transform each offer new views of the spatial and temporal courses of acute ischemia potentially leading to new diagnostic insights in ECG patient examination. PMID- 7884384 TI - Interdependence of corticosterone and thyroid hormones in toad larvae (Bufo boreas). II. Regulation of corticosterone and thyroid hormones. AB - Typically, the role of corticosterone(B) in metamorphosis is considered secondary to that of thyroid hormone, with B having only enhancing effects. In the current study, we demonstrate that the relationship between the thyroid hormones and B is much more complex and that thyroxine (T4) may depend on B for some of its functions. Tadpoles of the western toad (Bufo boreas) were treated with various combinations of corticosterone (B), thyroxine (T4), triiodothyronine (T3), a goitrogen (thiourea; Thio), and a corticoid synthesis inhibitor (metyrapone; MTP). Hormones were extracted from individual tadpoles and whole-body hormone levels determined by radioimmunoassay. B-treatment decreased the ratio of T4 to T3, suggesting that B increased the conversion of endogenous T4 to T3. In addition, B-treatment in combination with T4 resulted in high whole body-levels of T3. B also caused a decrease in whole body-thyroid hormone levels (T4 and T3), suggesting negative feedback on the hypothalamo-pituitary-thyroid axis and T3 had a similar effect, decreasing whole body-T4 levels. T4-treatment, but not T3, increased whole body-B levels and MTP-treatment in combination with T4 prevented the stimulatory effect of T4 on B production. MTP-treatment alone blocked all steroid metabolism of [3H]progesterone by the inter-renal in vitro, and lowered whole body-B levels three-fold in vivo. Thio-treatment reduced thyroid hormone levels and also resulted in decreased B. Finally, we suggest that these results demonstrate a system in which T4 may regulate its own potency: increasing T4 stimulates B production, which increases the conversion of T4 to its more active form T3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884385 TI - Factors influencing testosterone metabolism by anuran larvae. AB - The effects of experimental conditions--steroid concentration, temperature, treatment duration, tadpole density, and delivery mode--on testosterone (T) metabolic rates were examined in larval anurans. T uptake into tadpoles was measured by scintillation counting of [3H]T and metabolism of T was studied by thin layer chromatography in two anuran species, the African clawed frog (Xenopus laevis) and the western toad (Bufo boreas). T was extensively metabolized by both species, but the effects of each experimental condition on T metabolism varied between species. In the study of delivery mode, tadpoles injected with T dissolved in saline metabolized T faster than animals in groups where the steroid was added directly to the water. Animals injected with T dissolved in oil metabolized T the slowest, but T was short-lived in all cases. The current study demonstrates that concentration, temperature, treatment duration, tadpole density, and delivery mode may all affect steroid metabolic rates, but these effects vary between species in unpredictable ways. Since steroid metabolism may either activate or deactivate steroids, these factors are important in understanding the potency of steroids in tadpoles. A review of the literature dealing with steroid effects in anuran larvae illustrates these problems. PMID- 7884386 TI - Role of steroids in antler growth of red deer stags. AB - A series of six studies were carried out in red deer stags to test hypotheses concerning the importance of steroid control of velvet antler growth and to investigate mechanisms by which these hormones exert their effects. Medroxyprogesterone acetate (MPA) an LH inhibitor administered to stags during hard antler caused premature antler casting, reduced subsequent antler weight and caused a reduction in the LH and testosterone responses to GnRH. In two separate studies blockade of testosterone receptors with cyproterone acetate (CPA) administered to stags, either during early velvet antler growth or during the hard antler stage, significantly reduced LH and testosterone responses to GnRH. In both studies antler length, but not weight, was increased by CPA treatment. In another study testosterone implants were used to prevent the gradual decline in plasma testosterone levels normally observed during winter. Implants were removed 3 weeks before the anticipated date of antler casting. The implants significantly increased plasma testosterone levels and subsequent antler growth (expressed as a proportional increase compared with the previous year) compared with untreated controls. To determine whether the annual cycle of plasma testosterone response following GnRH stimulation was due simply to a lack of LH stimulation, ovine LH was injected on six occasions at defined stages of the antler cycle to red deer stags and the testosterone response measured. The testosterone responses were low at antler casting and during velvet antler growth compared with antler cleaning and peak rut. It appears low testosterone levels are due, in part, to a loss of responsiveness by the testes to LH as well as a low level of secretion of LH during the antler growing season. Finally synthetic ACTH was injected at the same defined stages of antler growth as in the previous study to determine whether cortisol and adrenal androgen production altered with the stage of the antler cycle. No significant differences were found in the dehydroepiandrosterone (DHEA) response, but cortisol responses were higher from late velvet antler growth to peak rut, compared with the times of antler casting and early velvet growth. Overall it was concluded that velvet antler growth can occur without testosterone stimulation during the period of velvet growth, but the data reinforce the concept that the timing of antler growth is linked to the annual cycle of testosterone. PMID- 7884387 TI - Effects of unilateral cranial sympathectomy either alone or with sensory nerve sectioning on pedicle growth in red deer (Cervus elaphus). AB - In a previous study (Li et al. [1993], J. Exp. Zool., 267:188-197) sensory nerve sectioning had no effect on the timing of pedicle growth. The aim of the present study was to determine whether sensory nerve sectioning in conjunction with sympathectomy would influence pedicle growth. Twelve intact male red deer calves were allocated to treatment before any pedicle growth as follows: 1) unilateral sensory nerve removal (USX, n = 5), 2) unilateral superior cervical ganglionectomy (SGX, n = 4), or 3) both USX and SGX (SG/USX, n = 3). The calves were observed weekly. In all cases the untreated side was the control. Pedicle initiation was measured with a pedicle detector and after initiation, growth was measured with a ruler. When the treated pedicles reached a length of 60 mm the calves were killed and tissues from the pedicle were examined immunohistochemically for nerves. No large bundles of nerves were observed in the treated pedicle although a few fine fibres were present. All calves grew pedicles. There were no significant differences in the timing of pedicle initiation either within treatment or between treatments. All denervated pedicles grew faster than controls and were consequently higher at examination. The fact that pedicle growth took place despite reduced innervation indicates that a continuous neural connection is not a pre-requisite for normal pedicle growth. PMID- 7884388 TI - Lysophosphatidylcholine treatment allows interspecies fertilization of hamster oocytes with zona pellucida by human spermatozoa. AB - The study of interspecific gamete interactions has been improved by the use of in vitro fertilization techniques. Zona pellucida is at the cellular level the main barrier to cross-fertilization. Moreover, there are several cases in which the heterologous spermatozoa fail to enter the cytoplasm of zona-free oocytes, emphasizing the notion that another important barrier exists to cross fertilization at the egg plasma membrane level. We report here a simple method to fertilize hamster oocytes with zona pellucida by human spermatozoa. We used lysophosphatidylcholine (LPC), a fusogenic agent, to treat spermatozoa, spermatozoa and zona-intact oocytes, or zona-intact oocytes alone. This molecule allows the penetration of hamster oocytes zona by human spermatozoa. Our results suggest that LPC modifies the zona pellucida of oocytes and the plasma membrane of both gametes in vitro, favouring sperm penetration through the zona pellucida and gamete fusion. PMID- 7884389 TI - Bone regrowth in young mice stimulated by nail organ. AB - Recent studies of postamputational repair following digit-tip amputation revealed an unexpected correlation between nail regrowth and bone regrowth in mice. To examine putative effects of nail on bone regrowth, phalangeal tips were amputated such that nail was artificially removed from distal levels or retained following proximal level amputations. In the absence of nail, bone did not regrow at distal levels. Conversely, when nail was surgically retained bone regrew from proximal levels. The nail organ profoundly influences bone regrowth. PMID- 7884390 TI - Studies on the autolysis of m-calpain from the skeletal muscle of the amphibian Rana ridibunda. AB - The autolytic mechanisms responsible for the regulation of m-calpain purified from the skeletal muscle of the amphibian Rana ridibunda were examined. Both subunits of the calpain molecule were found to undergo autolysis in the presence of Ca2+. Various divalent cations were examined for their ability to induce calpain autolysis. The concentrations of these cations required for the complete calpain autolysis were: 500 microM Ca2+, 800 microM Mn2+, 2 mM Sr2+, 10 mM Ba2+, whereas Mg2+, even at 10 mM did not induce any autolysis. Calpain autolysis induced by the above divalent cations is a temperature dependent process. Presence of Mn2+ or Sr2+ reduces the Ca2+ requirement of calpain for autolysis. The rate of autolysis depends on the protease concentration; protease inhibitors such as E-64, leupeptin, antipain, and iodoacetic acid inhibit the autolysis of calpain; E-64 inhibits irreversibly while leupeptin inhibits reversibly the autolysis; and irreversibly inactivated by E-64 calpain is fully digested by native calpain. Autolysis of calpain in the presence of alkali denatured casein increases the Ca2+ sensitivity of the protease for its half maximal and maximal caseinolytic activity. Limited autolysis of calpain is also induced in the presence of the endogenous substrate G-actin, and the rate of autolysis is slower than that obtained in the absence of substrates. PMID- 7884391 TI - Interdependence of corticosterone and thyroid hormones in larval toads (Bufo boreas). I. Thyroid hormone-dependent and independent effects of corticosterone on growth and development. AB - In a previous study (Hayes et al. [1993] J. Exp. Zool., 266:206-215), we demonstrated that exogenous corticosterone (B) inhibited growth, and had varied effects on development and metamorphosis in the toad (Bufo boreas). The current study determined the relation between the actions of B and thyroid hormones on body growth (length and weight), tail growth and reduction (length and height), rear leg growth and differentiation, and foreleg emergence (FLE). Thiourea (Thio; a goitrogen) and metyrapone (MTP; a glucocorticoid synthesis inhibitor) were used to determine the role of endogenous hormones in growth and development. These inhibitors were also used in various combinations with the thyroid hormones, thyroxine (T4) and triiodothyronine (T3), to determine the extent to which B's actions depend on the thyroid hormones. B was ineffective at inducing tail reduction (length and height) in the presence of Thio, but B enhanced the effects of both thyroid hormones, suggesting that the actions of B on the tail were dependent on thyroid hormones. B inhibited body growth even in the presence of Thio, but did not enhance thyroid hormone's inhibition of growth. B alone stimulated foreleg emergence (FLE) and enhanced thyroid hormone's activity on FLE when B and the thyroid hormones were given in combination, but did not induce FLE in the presence of Thio. B stimulated rear leg development, but not in the presence of Thio, suggesting that this effect was due to interactions with thyroid hormones. Furthermore, MTP antagonized the stimulatory effect of T4 on rear leg development, suggesting that endogenous B also interacted with exogenous thyroid hormones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884392 TI - The calcium ion and cell death. AB - There is now convincing evidence that the calcium ion can play a critical role in cell killing in the central nervous system and other tissues. Recent research has established some of the biochemical mechanisms by which intracellular Ca2+ overload can trigger either necrotic or apoptotic cell death, and a number of studies have shown that prevention of Ca2+ overload by pretreatment with either Ca2+ chelators, receptor antagonists or channel blockers can rescue cells that would otherwise die. Similarly, cells which express high levels of certain Ca(2+) binding proteins (e.g. calbindin-D28K) seem to be more resistant to killing. Thus, it appears that the development of improved strategies to prevent Ca2+ overload will be of importance for neuroprotection. The role of the calcium ion as intracellular regulator of many physiological processes is now well established. Thus, the effects of a variety of hormones and growth factors have been found to be mediated by transient increases in the level of cytosolic Ca2+, which frequently assume oscillatory patterns (see Carafoli, 1989 and Berridge, 1991 for reviews). Most often, the Ca2+ increase is initiated by the release of Ca2+ from intracellular stores followed by the stimulation of influx of extracellular Ca2+. Most regulatory effects of Ca2+ are mediated by Ca(2+) binding proteins (e.g. calmodulin) and achieved by alterations of the phosphorylation state of target proteins. Along with this knowledge has come the understanding that Ca2+ can also play a determinant role in a variety of pathological and toxicological processes. It has long been recognized that Ca2+ accumulates in necrotic tissue, and more recent work has revealed that a disruption of intracellular Ca2+ homeostasis is frequently associated with the early development of cell injury (Schanne et al., 1979; Jewell et al., 1982; Fleckenstein et al., 1983). This led to the formulation of the calcium hypothesis of cell injury, proposing that perturbation of intracellular Ca2+ homeostasis may be a common step in the development of cytotoxicity. Support for this hypothesis has come from a large number of studies demonstrating that the calcium ion plays a critical role in cytotoxicity and cell killing in many tissues, notably the central nervous system and the immune system (see Nicotera et al., 1992 for review). PMID- 7884393 TI - The enigma of neuromelanin in Parkinson's disease substantia nigra. AB - The function of neuromelanin accumulation in the nigrostriatal dopamine neurons remains uncertain. Nevertheless, it is recognized that neuromelanin disappearance parallels the loss of dopamine neurons in Parkinson's disease, suggesting its participation in nigral cell death. It has been well known for some years that in systemic tissues melanin is a double-edged sword. On the one hand it can act as an antioxidant, but in the presence of transitional metals (primarily, iron) and drugs it promotes the formation of reactive oxygen free radicals. It is now apparent that synthetic dopamine-melanin and neuromelanin exhibit similar properties in vitro and nigrostriatal dopamine neuron co-culture studies. Thus, the identification of ionic iron in dopamine neurons of Parkinson's disease zona compacta and its association with neuromelanin has conferred a cytotoxic property to neuromelanin. This may explain the reported vulnerability of substantia nigra dopamine neurons in Parkinson's disease. PMID- 7884394 TI - Blood to brain iron uptake in one rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol. AB - Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson's disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood. PMID- 7884395 TI - Clinical experiences with nimodipine in cerebral ischemia. AB - Increased intracellular calcium is involved in the death of neurons associated with cerebral ischemia. After extensive experimental work, the calcium antagonist nimodipine has been investigated in several clinical trials in patients with disorders of the cerebral circulation. A short overview on trials in subarachnoid hemorrhage, head injury, ischemic stroke and cerebral resuscitation is given in this paper. PMID- 7884396 TI - MPTP-induced degeneration: interference with glutamatergic toxicity. AB - Parkinson's disease (PD) is characterised by the progressive degeneration of nigrostriatal dopamine (DA) neurons resulting in the major symptoms of akinesia and rigidity. Although the primary cause of PD is still not known some features make this disorder a model for neurodegenerative diseases in general. It has been known for some time that symptomatic PD can be attributed to insults with symptoms occurring many years later such as post-encephalitic PD or PD following manganese poisoning. More recently, MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine) has been identified as a neurotoxin selective for melanin containing dopaminergic neurons in humans and non-human primates. The specificity of this neurotoxin and the striking clinical similarities to idiopathic PD, seen in primates, make MPTP-induced parkinsonism the most useful animal model of a neurological disease. There are numerous theoretical possibilities to interfere with both MPTP-induced neurotoxicity and the symptomatology of PD. In recent years excitatory amino acids have gained considerable interest since they can cause excitotoxic lesion of neurons under a number of pathological conditions (Olney et al., 1989; Choi, 1988). Here we summarise the present data and provide new experimental evidence indicating that MPTP-induced degeneration of dopaminergic neurons does involve glutamate-mediated toxicity. It is concluded that glutamate-mediated excitotoxicity results in the destruction of DAergic somata in the substantia nigra. Non-competitive or competitive NMDA antagonists protect nigral neurons from MPTP-induced degeneration whereas their striatal terminals still seem to degenerate. PMID- 7884397 TI - Influence of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, lipoic acid and L deprenyl on the interplay between cellular redox systems. AB - For several years there is controversy concerning the toxic potency of reaction products catalyzed by monoamine oxidase in neurodegenerative processes. There is uncertainty whether products of catecholamine oxidation are pathogenetically relevant factors for neuronal cell death in Parkinson's disease. To date products responsible for impairment of biochemical functions essential for cell viability are not yet identified, and the primary site of damage within the cell is unknown. Ammonia, aldehydes and hydrogen peroxide are formed via monoamine oxidase catalyzed oxidations of primary amines. But which of them, if any, is damaging to the cell? We discuss some aspects of the oxidative stress theory of cell degeneration in relation to toxicity of N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) and to monoamine oxidation. Furthermore, we consider possible functional relationships of mitochondrial electron transfer reactions, toxicity of MPTP and MAO activity. PMID- 7884398 TI - Clinical aspects of neuroprotection in Parkinson's disease. AB - Clinically a neuroprotective effect can only be presumed under the assumption that impairment of Parkinsonian symptoms, cellular dysfunction and cell degeneration are correlated. From the clinical point of view there is no real chance to demonstrate these correlations. For this reason it seems to be more realistic to differentiate between neuroprotective and functional neuroprotective effects. Bromocriptine as well as selegiline seem to have a functional neuroprotective effect. PMID- 7884399 TI - Clinical trials of neuroprotection in Parkinson's disease: long-term selegiline and alpha-tocopherol treatment. AB - Attempts to lessen the progression of Parkinson's Disease (PD) have made use of 2 strategies: inhibition of monoamine oxidase type B with deprenyl (selegiline) and the free radical trapping agent alpha-tocopherol (vitamin E). Clinical trials exploring these possibilities have suggested that deprenyl can alter the natural course of PD, although the mild symptomatic effects produced by this drug confound the analysis of its possible protective actions. Alpha-tocopherol conferred no neuroprotection. Since deprenyl produces a variety of pharmacological effects, the results of the DATATOP and related clinical studies with this drug are subject to several alternative explanations. PMID- 7884400 TI - Neuroprotection by dopamine agonists. AB - Research on Parkinson's disease has led to new hypotheses concerning the mechanisms of neurodegeneration and to the development of neuroprotective agents. Recent findings of impaired mitochondrial function, altered iron metabolism and increased lipid peroxidation in the substantia nigra of parkinsonian patients emphasize the significance of oxidative stress and free radical formation in the pathogenesis of Parkinson's disease. Present research is therefore focussing on improvements in neuroprotective therapy to prevent or slow the rate of progression of the disease. Possible neuroprotective strategies include free radical scavengers, monoamine oxidase-B inhibitors, iron chelators and glutamate antagonists. Recent studies point to the possibility of achieving neuroprotection in ageing and parkinsonism by the administration of dopamine agonists. In the rat, the dopamine agonist pergolide appears to preserve the integrity of nigrostriatal neurones with ageing. The prevention of age-related degeneration may be achieved as a result of a decreased dopamine turnover and reduced conversion of dopamine to toxic compounds. In our own study, bromocriptine treatment prevented the striatal dopamine reduction following MPTP administration in the mouse. These results suggest that the neurotoxic effects of MPTP can be prevented by bromocriptine. Monotherapy with the dopamine agonist lisuride in the early stages of Parkinson's disease delays the need for the initiation of levodopa treatment to a similar extent as has been reported for L-deprenyl. It remains to be shown whether this is due to neuroprotective efficacy of the dopamine agonist or to a direct symptomatic effect. PMID- 7884401 TI - Hypothalamic dysfunction in dementia. AB - In 40 patients with Alzheimer's disease (AD) 56 patients with senile dementia of Alzheimer type (SDAT) and 45 patients with vascular dementia (VAD) degree of dementia was rated into mild, moderate and severe according to DSM-III-R and on the GBS scale. Basal cortisol levels were determined and a dexamethasone test (DST) performed. Basal cortisol levels were high in all the dementia groups. Forty percent of AD patients, 54% of SDAT patients and 49% of VAD patients were non suppressors. Significant correlations between post DST cortisol levels and rated variables were seen mainly in the VAD group. The pathological DST could hardly be explained by presence of depression. In dementia, especially those with white matter disturbances, disconnections between cortical areas (hippocampus) and hypothalamus can be assumed explaining a reduced inhibitory tone on hypothalamus. When characterizing VAD patients with pathological DST these patients were significantly more intellectually impaired, showed higher degree of anxiety, restlessness and fear-panic than VAD patients with normal DST. Some behaviourial disturbances in dementia disorders may be a consequence of HPA over activity rather than a consequence of the dementia process itself. PMID- 7884402 TI - Therapy of Alzheimer disease: symptomatic or neuroprotective? AB - Therapeutic strategies aimed to treat Alzheimer disease (AD) may either produce an attenuation of symptoms or slow down deterioration by attenuating progression of the disease. Presently, cholinesterase inhibitors (ChEI) have shown the most promising therapeutical effects. The best documented clinical efficacy of ChEI are studies of THA (tacrine, tetrahydroaminoacridine). The results of five recent studies in a total of 1,242 patients are reported here. Based on differences from placebo in scoring, a gain of 2-12 (MMSE) or 5-6 (ADAS) months in deterioration can be seen for a THA treatment of 2-3 months duration. This suggests that if treatment with THA will be extended to a longer period, the drug effect may not be only a symptomatic improvement but a slow-down of disease course. A similarity of THA's effect in AD with L-deprenyl effects in Parkinson is suggested. PMID- 7884403 TI - Pharmacological evaluation of phenyl-carbamates as CNS-selective acetylcholinesterase inhibitors. AB - The pharmacological and clinical properties of a novel phenyl carbamate acetylcholinesterase (AChE) inhibitor, SDZ ENA 713 are described. In animals and human subjects this compound showed superior chemical stability, oral bioavailability and a longer duration of action than physostigmine. SDZ ENA 713 produced a 10-fold greater inhibition of AChE in the hippocampus and cortex than in the heart and skeletal muscle, which explains its relatively low toxicity and freedom from cholinergic side effects. The selective effect in the cortex and hippocampus may be due to its preferential inhibition of the G1 form of the enzyme, which is present in relatively higher concentrations in these brain areas. Evidence of a selective hippocampal action was obtained in normal human subjects in whom REM sleep density was increased at doses that had no effect on plasma cholinesterase. If memory impairments in AD are related to a lack of cholinergic activity in cortical and hippocampal brain areas, SDZ ENA 713 should produce significant symptomatic improvement. PMID- 7884404 TI - Adenosine--an endogenous neuroprotective metabolite and neuromodulator. AB - Adenosine is now widely accepted as the major inhibitory neuromodulator in the central nervous system besides GABA. It has been suggested to be an endogenous neuroprotective metabolite. In situations of metabolic stress, e.g. ischemia adenosine decreases energy demand and increases energy supply. Of particular relevance in this context is its modulation of glutamate release. A shift of this adenosine-glutamate balance in favor of adenosine helps to restore function at the cellular, organ and organism level. Adenosine A1 receptor agonists and metabolic inhibitors, e.g. of transport, deaminase and xanthine oxidase have been demonstrated to be effective in different animal models of ischemia. Nimodipine, a L-type channel calcium antagonist currently in clinical trials for stroke and dementia syndromes, has now been shown to be a potent adenosine transport inhibitor in clinically relevant concentrations. Increase of adenosinergic neuromodulation may well be one of several future therapeutic strategies in neuroprotection. PMID- 7884405 TI - Neuroprotective effects of TGF-beta 1. AB - The transforming growth factor-beta 1 (TGF-beta 1) has been shown to be an injury related peptide growth factor within the mammalian brain. We tested TGF-beta 1 for its protective effects against neuronal degeneration caused by sodium cyanide (1 mM) or by the excitatory amino acid L-glutamate (1 mM) in vitro and against ischemic injury in vivo caused by permanent occlusion of the left middle cerebral artery in mice. In vitro, TGF-beta 1 (1-30 ng/ml) significantly reduced hypoxic and excitotoxic neuronal damage in a concentration-dependent manner. In vivo, intracerebroventricular administration of TGF-beta 1 (1 microgram/kg) decreased the infarcted area on the mouse brain surface. The present results suggest that TGF-beta 1 is capable of protecting neurons against damage both in vitro and in vivo. PMID- 7884406 TI - New mechanisms of excitatory transmitter neurotoxicity. AB - Accumulating evidence suggests that either excessive activation or suppression of either ionotropic or metabotropic EAA receptors can have neurotoxic consequences, and a variety of different mechanisms may be involved. The major excitatory neurotransmitters in the mammalian CNS-glutamate (Glu) and acetylcholine (ACh)- have vitally important beneficial functions, but also harbor treacherous neurotoxic potential which, as will be described in this review, can be expressed as classical excitotoxicity or in several other ways that have yet to be studied in detail. PMID- 7884407 TI - The glycine binding site of the NMDA receptor: involvement in neurodegeneration and new approach for neuroprotection. AB - Excitatory amino acids may have a neurotoxic effect in acute and chronic neurodegenerative diseases. Glutamate mediated Ca-influx into the cell is caused by activation of the NMDA-receptor. In addition to the competitive binding site there is a glycine binding site at the NMDA-receptor, where in an agonistic function glycine leads to opening of the ion channel. Antagonists at this glycine binding site may reduce the Ca-influx and thereby have a neuroprotective effect. The affinity of HA-966 to the glycine binding site in human hippocampus brain tissue is in the low micromolar range (Ki = 8.1 +/- 1.5 microM). So HA-966 may play a role as a neuroprotective substance. PMID- 7884408 TI - Behavioural effects of NMDA-receptor antagonists. AB - NMDA receptor-antagonists were tested in dose ranges that have previously been found to produce anticonvulsant and anticataleptic (antiparkinsonian) effects in rats. Non-competitive NMDA receptor-antagonists had strong psychomotor stimulating effects, the competitive ones were weaker in this respect when given systemically. However, when locally injected into the striatum or into the nucleus accumbens, also the competitive NMDA-antagonists induced psychomotor stimulation. If at all, NMDA receptor-antagonists have rewarding effects, then they seem to be elicited only by the non-competitive NMDA receptor-antagonists. In maze tests, sensitive for hippocampally mediated learning, NMDA receptor antagonists impaired learning. While non-competitive NMDA-antagonists produced learning deficits over the whole dose range tested, competitive ones were only effective at higher dose levels. PMID- 7884409 TI - Glutamate receptor antagonists in cerebral ischaemia. AB - Glutamate mediated neuronal death has been implicated in every human neurodegenerative disease, but cerebral ischaemia is the area where the modulation of excitotoxicity is closest to providing a new therapeutic avenue. In cerebral ischaemia there is a marked, immediate increase in the extracellular concentration of glutamate, irrespective of the nature and primary cause of the ischaemic episode. Elevations in the extracellular concentrations of glutamate lead to excessive activation of the glutamate NMDA and AMPA receptor subtypes initiating a sequence of neurochemical events which lead ultimately to neuronal death. Animal models of focal cerebral ischaemia have been particularly influential in defining the anti-ischaemic effects of agents which block NMDA or AMPA receptors or which putatively reduce glutamate release. The systemic generation of anti-ischaemic efficacy data which addresses every contentious issue has been crucial for the progression of these agents to man. PMID- 7884410 TI - The competitive NMDA receptor antagonist CGP 40116 is a potent neuroprotectant in a rat model of focal cerebral ischemia. AB - Focal cerebral ischemia was induced in rats by permanent occlusion of the left middle cerebral artery (MCA). The cerebroprotective properties of the competitive NMDA antagonist CGP 40116 were evaluated in that model and compared to the neuroprotective effects of MK 801, D-CPPene and CGS 19755 under the same experimental conditions. Infarct volume was assessed using in vivo magnetic resonance imaging. The rank order of potency for the NMDA antagonists tested was MK 801 > CGP 40116 approximately D-CPPene > CGS 19755. CGP 40116 dose-dependently reduced the volume of cortical infarction, with an ED50 of 11 mg/kg i.v., and its cerebroprotective efficacy was comparable to that of MK 801. Neuroprotection by CGP 40116 was still apparent when treatment was started 30 minutes after MCA occlusion. It is concluded that CGP 40116 is an effective cerebroprotectant with potential clinical utility for amelioration of focal cerebral ischemic damage. PMID- 7884412 TI - Preoperative chemotherapy: a model for studying the biology and therapy of primary breast cancer. PMID- 7884411 TI - Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties. AB - The pharmacological inhibition of excitatory amino acid neurotransmission has evolved to be a major topic in neuropharmacology since enhanced synaptic action of glutamate and possibly other related neurotransmitters has been suggested to play a role both in acute neurological conditions such as ischemia and epilepsy and in chronic degenerative neurological diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. While antagonists at N-methyl-D aspartate (NMDA) type glutamate receptors include psychotomimetic and neurotoxic agents such as phencyclidine and MK-801, the aminoadamantanes represent a class of drugs which may be largely free of such actions and which have already been used clinically as antiviral and antiparkinsonian agents. Multiple in vitro studies have recently delineated the neuroprotective properties of amantadine, and of its more potent congener, memantine, which appear to mediate neuroprotection via inhibition of NMDA receptor-dependent glutamate activity. Thus, neuroprotection targeting glutamate receptors does apparently not have to be associated with prominent psychotogenicity, and the development and evaluation of new neuroprotective drugs will have to performed in consideration both of the relative safety and of the good clinical effect of the already known and established aminoadamantanes. PMID- 7884413 TI - Current approaches to hematopoietic stem-cell purging in chronic myeloid leukemia. PMID- 7884414 TI - Randomized trial of chemoendocrine therapy started before or after surgery for treatment of primary breast cancer. AB - PURPOSE: To evaluate in a randomized clinical trial systemic chemoendocrine therapy used as primary (neo-adjuvant) treatment before surgery in women with primary operable breast cancer. PATIENTS AND METHODS: Patients aged less than 70 years with clinically palpable, primary operable breast cancer diagnostically confirmed by fine-needle aspiration cytology (FNAC) and suitable for treatment with surgery, radiotherapy, cytotoxic chemotherapy, and tamoxifen were considered eligible. Patients randomized to neoadjuvant treatment received four cycles of chemo-therapy for 3 months before surgery followed by another four cycles after surgery, and were compared with patients randomized to adjuvant therapy who received eight cycles of chemotherapy over 6 months after surgery. RESULTS: Of 212 patients who were randomized to receive either adjuvant (n = 107) or neoadjuvant (n = 105) chemoendocrine therapy, 200 are now assessable for response. The two groups are comparable for age, menopausal status, disease stage, and surgical requirements. The overall clinical response rate was 85%, with a complete histologic response rate of 10%. There was a significant reduction in the requirement for mastectomy in patients who received neoadjuvant treatment (13%) as compared with those who received adjuvant therapy (28%) (P < .005). Symptomatic and hematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. The median follow-up period for patients in this trial is 28 months, during which time four patients have relapsed locally and 20, including one of the local relapses, have developed metastatic disease, 19 of whom have died. The follow-up period is too brief to evaluate relapse rate or survival duration. CONCLUSION: This trial confirms previous reports of a high rate of response to neoadjuvant therapy, but is the first to include small primary cancers and to show, in the context of a randomized trial, a reduction in the requirement for mastectomy. Until disease-free and overall survival data are available from the larger National Surgical Adjuvant Breast and Bowel Project (NSABP)-18 trial, such neoadjuvant treatment cannot be recommended outside of a clinical trial. PMID- 7884415 TI - Collection of peripheral-blood diploid cells from chronic myelogenous leukemia patients early in the recovery phase from myelosuppression induced by intensive dose chemotherapy. AB - PURPOSE: To evaluate whether intensive chemotherapy followed by peripheral stem cell (PSC) collections during early hematopoietic recovery results in a higher percentage of diploid cell collections in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). PATIENTS AND METHODS: Fifty five adults with Ph-positive CML received intensive chemotherapy with daunorubicin and high-dose cytarabine (ara-C) (DAUNO-HDAC; 26 patients) or fludarabine, high-dose ara-C, and mitoxantrone (FAM; 29 patients). Collections of the peripheral mononuclear cells were initiated when the WBC count was > or = 0.8 x 10(3)/microL. Simultaneous peripheral and marrow samples were subjected to cytogenetic studies. RESULTS: Thirty-eight of 55 patients (69%) were able to undergo the PSC collections. The rate of collection was higher in chronic phase (26 of 30 patients; 87%) than in accelerated (11 of 17; 65%) and blastic phases (1 of 8; 12%). Among the 30 patients in chronic phase, cytogenetic analyses of PSC showed cytogenetic responses (Ph-positive < 95%) in 60%, which were major (Ph < 35%) in 43% and complete (Ph = 0%) in 27%. Seven of 19 patients with simultaneous studies (37%; 23% of total) had a significantly lower percentage of Ph-positive cells in the peripheral collection compared with the marrow collection; one had the reverse phenomenon (5%; 3% of total). Cytogenetic responses were modest in both peripheral and marrow collections in CML accelerated and blastic phases. Myelosuppression-associated complications were frequent, resulting in febrile episodes in 76% of patients. CONCLUSION: PSC collection during early hematopoietic recovery from intensive chemotherapy allowed the collection of diploid-rich stem cells, mostly in chronic-phase CML. The approach could be used for in vivo purging before autologous stem-cell transplantation (ASCT). PMID- 7884416 TI - Improved survival for patients with acute myelogenous leukemia. AB - PURPOSE: Despite improvement in chemotherapy and supportive care over the past two decades, overall survival for patients with acute myelogenous leukemia (AML) remains poor; only 25% to 30% of individuals with this disorder will be cured. In 1987, we initiated a prospective multiinstitution study designed to improve long term survival in adults with AML. METHODS: We modified the usual 7-day treatment scheme of daunorubicin and cytarabine with high-dose cytarabine (HiDAC) on days 8 through 10 (3 + 7 + 3). Allogeneic or autologous bone marrow transplantation (BMT) was offered to all patients who entered complete remission (CR) to decrease the rate of leukemic relapse. Data were analyzed by intention to treat. RESULTS: CRs were achieved in 84 of 94 patients (89%; 95% confidence interval [CI], 83 to 95). Because of the high remission rate, factors previously thought to predict outcome, such as cytogenetics, WBC count, French-American-British (FAB) classification, sex, and age, were not useful prognostic variables. The overall survival rate for the entire cohort of patients from data of diagnosis is 55% at 5 years. Sixty percent of all patients who achieved a CR underwent marrow grafting. There was no significant difference in event-free survival (EFS) at 5 years comparing patients assigned to receive allogeneic BMT with patients assigned to receive autologous BMT (56% v 45%, P = .54). CONCLUSION: The long term disease-free survival observed in this study is excellent compared with historical data. This improvement in survival is probably due to the high rate of remission induction, as well as to the effective nature of the consolidation therapy. PMID- 7884417 TI - 2-Chlorodeoxyadenosine activity in patients with untreated chronic lymphocytic leukemia. AB - PURPOSE: 2-chlorodeoxyadenosine (2-CdA; cladribine) is a purine analog with activity in patients with chronic lymphocytic leukemia (CLL) who fail to respond to alkylator therapy. We conducted a phase II trial of 2-CdA in previously untreated CLL patients. PATIENTS AND METHODS: 2-CdA was administered to 20 patients with previously untreated CLL as a 0.1-mg/kg/d 7-day continuous intravenous infusion every 28 to 35 days until maximum response or prohibitive toxicity. RESULTS: A median of four courses (range, one to nine) was administered to each patient. Five patients (25%) achieved a complete response and 12 (60%) achieved a partial response, for an overall response rate of 85%. The median response follow-up duration was 8+ months (range, 3 to 27). Myelosuppression was the principal toxicity. Four of 20 patients (20%) experienced grade III or IV thrombocytopenia. Three patients, all of whom received corticosteroid therapy, developed opportunistic infections at a median of 19 months following discontinuation of 2-CdA therapy. CONCLUSION: 2-CdA has major activity in patients with previously untreated CLL, and the lower response rates seen in previously treated patients may be due in part to poor marrow reserve from prior therapy. Determination of the relative effectiveness of 2-CdA, fludarabine, and chlorambucil in the treatment of CLL patients will require a randomized trial. PMID- 7884418 TI - Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma. AB - PURPOSE: Interleukin-6 (IL-6) is a potent immunomodulatory cytokine that may have pathogenetic and prognostic significance in a number of disorders. The objective of this study was to examine the correlation between serum IL-6 levels and phenotypic characteristics, as well as outcome of patients with diffuse large cell lymphoma (DLCL). PATIENTS AND METHODS: Using an enzyme-linked immunosorbent assay (ELISA; lower limit of sensitivity, 0.35 pg/mL), we measured IL-6 levels in frozen sera from 33 healthy controls and 58 untreated patients with DLCL who were enrolled onto a single combination chemotherapy protocol. Serum IL-6 levels were correlated with clinical and laboratory features at diagnosis and with failure free and overall survival. RESULTS: Serum IL-6 levels in the lymphoma patients (median, 4.37 pg/mL; range, < 0.35 to 110 pg/mL) were significantly higher than in the control group (median, < 0.35 pg/mL; range, < 0.35 to 1.87 pg/mL) (P < .0001). Serum IL-6 levels were higher in patients with B symptoms (P = .012), an elevated beta 2-microglobulin level (> or = 3.0 mg/L) (P = .017), and a poor performance status (P = .02). Direct linear correlations with the erythrocyte sedimentation rate (ESR), platelet count, and total WBC count, and an inverse linear correlation with the serum albumin level, were observed (all P < .02). Patients with elevated serum IL-6 levels had inferior failure-free (P = .042) and overall survival (P = .05) compared with those with normal serum IL-6 levels. CONCLUSION: In patients with DLCL, elevated serum levels of IL-6 at diagnosis are frequent, strongly associated with many adverse disease features, and predictive of a poor failure-free and overall survival. PMID- 7884419 TI - Three-hour paclitaxel infusion in patients with refractory and relapsed non Hodgkin's lymphoma. AB - PURPOSE: Paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) is a novel antimicrotubule agent with anti-tumor activity against ovarian and breast carcinomas. Its activity when administered as a 3-hour intravenous infusion in patients with relapsed non-Hodgkin's lymphoma (NHL) has not been studied. PATIENTS AND METHODS: Patients with relapsed NHL were treated with a 3-hour infusion of 200 mg/m2 of Taxol every 3 weeks in an outpatient setting. All patients received premedication (dexamethasone, diphenhydramine, and cimetidine) to prevent allergic reactions. Responses were assessed after two courses of therapy, and patients who achieved at least partial remission (PR) continued to receive Taxol for a maximum of eight courses. RESULTS: Of 60 eligible patients, 54 (90%) were assessable for treatment toxicity and 53 (88%) were for treatment response (22 with primary refractory and 31 with relapsed disease). Twelve patients (23%) achieved a PR (n = 6) or complete remission (CR; n = 6) (95% confidence interval, 12% to 36%). Responses were observed in intermediate-grade (31%), low-grade (14%), and mantle-cell (17%) lymphomas. In the intermediate grade lymphomas, there was a trend for a higher response rate in relapsed versus primary refractory disease (54% v 13%; P = .08). Treatment-related toxicity included alopecia (100%), peripheral neuropathy (37%), myalgia or arthralgia (25%), and neutropenic fever (11%). None of the patients had allergic reactions or cardiac toxicity. CONCLUSION: At this dose and schedule, Taxol is an active agent in patients with relapsed NHL and can be safely administered in an outpatient setting. Combination programs with Taxol should be investigated for treatment of NHL. PMID- 7884420 TI - BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin's lymphoma. AB - PURPOSE: To evaluate the outcome of patients with relapsed or resistant non Hodgkin's lymphoma (NHL) undergoing high-dose chemotherapy and autologous bone marrow transplantation (ABMT) and to determine the main prognostic factors. PATIENTS AND METHODS: One hundred seven patients with relapsed or resistant intermediate-/high-grade NHL underwent high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy and ABMT at University College Hospitals between September 1981 and February 1993. The minimum follow-up duration of all patients is 6 months. RESULTS: At 3 months, the overall response rate to BEAM and ABMT was 73% (41% complete response and 32% partial response). The 5-year actuarial overall survival and progression-free survival rates were 41% and 35%, respectively. The early procedure-related mortality rate was 7% (eight of 107 patients). On multivariate analysis, the main prognostic factor was disease status at the time of ABMT. Patients with chemosensitive disease had an actuarial 5-year survival rate of 49% at 5 years compared with 13% for those with chemoresistant disease (P < .001). For patients considered to have chemosensitive disease at the time of transplantation, there is a significant difference in the actuarial progression-free survival rates for those who received high-dose therapy after attaining a partial response to first-line therapy (69% at 5 years) as compared with those with sensitive but relapsed disease (32% at 5 years) (P = .003). CONCLUSION: Patients with chemosensitive disease benefit most from high dose chemotherapy, and those who receive such therapy early after achieving a partial response to first-line therapy have a high rate of cure. PMID- 7884421 TI - High-dose cyclophosphamide, carmustine, and etoposide followed by allogeneic bone marrow transplantation in patients with lymphoid malignancies who had received prior dose-limiting radiation therapy. AB - PURPOSE: To evaluate a high-dose chemotherapy regimen without total-body irradiation (TBI) followed by allogeneic (allo) bone marrow transplantation (BMT) in patients with lymphoid malignancies who had received prior dose-limiting radiotherapy. PATIENTS AND METHODS: Fifty-six patients with non-Hodgkin's lymphoma (NHL, n = 26), Hodgkin's disease (HD, n = 17), or acute lymphoblastic leukemia (ALL, n = 13) with a history of previous radiation therapy were treated with cyclophosphamide (7.2 g/m2), carmustine (300 mg/m2 or 600 mg/m2), and etoposide (2,400 mg/m2; CBV) followed by allo BMT. RESULTS: Nine of 56 patients are alive and disease-free a median of 1,091 (range, 512 to 1,784) days post transplant. The probabilities of transplant-related mortality, relapse, and event free survival at 2 years for the entire group of 56 patients were .62, .59, and .17, respectively. Patients who received 600 mg/m2 of carmustine had a higher incidence of grade 3 or 4 regimen-related toxicities (RRTs) (14 of 22) than did patients who received 300 mg/m2 (12 of 33; P < .04), whereas there was no difference in relapse (.34 and .53, respectively, P = .73). Fourteen of 16 patients who received allo BMT for advanced disease (n = 12) or less-advanced disease (n = 4) but who were also eligible for auto BMT relapsed (n = 4) or died of transplant-related complications (n = 10). CONCLUSIONS: Allo BMT following a high-dose CBV regimen resulted in long-term disease-free survival in 17% of patients with lymphoid malignancies who had received prior dose-limiting radiotherapy. A high incidence of transplant-related complications, especially fatal idiopathic pneumonia syndrome (IPS) and a high relapse rate limited success. Morbidity and mortality associated with carmustine 600 mg/m2 were high and were not associated with a decrease in relapse. The number of patients in this study eligible for either allo or auto BMT was limited and precluded meaningful analysis of relative effectiveness. PMID- 7884422 TI - Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease. AB - PURPOSE: We assessed the cumulative risk of malignancies following treatment for Hodgkin's disease in childhood and adolescence and investigated related patient and treatment characteristics. PATIENTS AND METHODS: Medical records of 499 Hodgkin's disease patients treated between 1962 and 1993 were reviewed. There were 385 adolescents (> or = 10 years of age at diagnosis) and 114 preadolescents (< 10 years). Most patients (n = 346) were treated with radiation plus multiagent chemotherapy, while 30 received only chemotherapy and 123 only radiation therapy. Radiation doses ranged from 20 to 42 Gy. RESULTS: At a median follow-up duration of 9 years (range, 0.1 to 27.4), 25 patients have had second malignancies: 19 solid tumors, four acute nonlymphoblastic leukemias (ANLLs), 1 non-Hodgkin's lymphoma (NHL), and one chronic myeloid leukemia (CML). Three patients have had a third malignancy. The estimated cumulative risk of second malignancies increased from 1.5% at 5 years to 7.7% at 15 years. All but two of the patients with second malignancies were > or = 10 years of age at initial diagnosis, which reflects the higher risk among patients treated for Hodgkin's disease as adolescents (P = .01). Second malignancies were more common among female patients (P = .0002), even when those breast cancer were excluded (P = .007), and in those treated for recurrent Hodgkin's disease (P = .02). Patients with ANLL/NHL were older at diagnosis of Hodgkin's disease than those with solid tumors, (median age, 18.3 v 13.8 years; P = .04). There was no difference between groups treated with radiation therapy alone, chemotherapy alone, or radiation plus multiagent chemotherapy. CONCLUSION: Adolescents treated for Hodgkin's disease are at greater at risk of second malignancies than younger patients. Overall, adolescent females treated for recurrent Hodgkin's disease appear to be at greatest risk, while preadolescents appear to be protected from this late complication. PMID- 7884423 TI - The Third Intergroup Rhabdomyosarcoma Study. AB - PURPOSE: The ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation. PATIENTS AND METHODS: One thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression-free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984). RESULTS: The overall outcome of therapy in IRS-III was significantly better than in IRS-II (5 year PFS, 65% +/- 2% v 55% +/- 2%; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine and dactinomycin (VA), as did a comparable group treated with VA plus cyclophosphamide (C) (5-year PFS, 83% +/- 3% v 76% +/- 4%; P = .18). Results for patients with group II favorable-histology tumors, excluding orbit, head, and paratesticular sites, were inconclusive regarding the benefit from addition of doxorubicin (ADR) to VA. Patients with group III tumors, excluding those in special pelvic, orbit, and other selected nonparameningeal head sites, fared much better on the more intensive regimens of IRS-III than on pulsed VAC or VAC-VADRC in IRS-II (5-year PFS estimates, 62% +/- 3% v 52% +/- 3%; P < .01); however, there were no significant differences in outcome among the groups treated in IRS III. Patients with metastatic disease at diagnosis (clinical group IV) did not benefit significantly from the more complex therapies evaluated in IRS-III. CONCLUSION: Intensification of therapy for most patients in IRS-III, using a risk based study design, significantly improved treatment outcome overall. The largest gain from this strategy was realized in patients with gross residual tumor after biopsy (clinical group III). It was also possible to decrease therapy for selected patient subsets without compromising survival. PMID- 7884424 TI - Use of intracavitary cisplatin for the treatment of childhood solid tumors in the chest or abdominal cavity. AB - PURPOSE: Intracavitary (IC) delivery of cisplatin (CDDP) has been used in the treatment of a variety of adult malignancies based on the favorable pharmacokinetics obtained locally. Since IC CDDP has not been reported in children, we studied its use in a group of pediatric patients with regard to safety, toxicity, pharmacokinetics, and responses. PATIENTS AND METHODS: Eleven patients with an age range of 8 months to 21 years with diagnoses of rhabdomyosarcoma (n = 5), pleuropulmonary blastoma (n = 2), osteosarcoma (n = 2), Ewing's sarcoma (n = 1), and malignant rhabdoid tumor of the kidney (n = 1) were studied. Eight patients received intrapleural (IPL) CDDP and three received intraperitoneal (IP) CDDP, either at diagnosis (n = 3) or relapse (n = 8), for malignant pleural effusion (n = 3), malignant ascites (n = 2), pleural-based tumor (n = 4), pulmonary metastases (n = 1), or abdominal tumor spillage (n = 1). RESULTS: IC CDDP was well tolerated by pediatric patients. Two patients experienced a transient increase in serum creatinine levels (> two times baseline) and two patients experienced severe neutropenia (absolute neutrophil count < 500/microL). Pharmacokinectic measurements showed a 40-fold advantage for the pleural cavity versus serum after IPL CDDP and serum levels comparable to those achieved with systemic administration of CDDP. Four of five patients who received IC CDDP for malignant ascites or pleural effusion had at least a temporary response. Only three of 11 patients studied had local recurrences following IC CDDP. There are currently four survivors in the study group, including two long-term survivors at greater than 8 years since IPL CDDP treatment. CONCLUSION: The safety, toxicity, and pharmacokinetics of IC CDDP in pediatric patients are similar to that reported in adult patients. The low incidence of local recurrence following IC CDDP in this group of largely relapsed patients suggests that further study of IC CDDP for pediatric patients is warranted. PMID- 7884425 TI - Phase II study of docetaxel for advanced or metastatic platinum-refractory non small-cell lung cancer. AB - PURPOSE: We conducted a phase II study to determine the response to and toxicity of docetaxel (Taxotere; Rhone-Poulenc Rorer Pharmaceuticals, Inc, Collegeville, PA) in patients with advanced non-small-cell lung cancer refractory to prior platinum-containing chemotherapy (PCC) regimens. PATIENTS AND METHODS: Forty-four patients with stage IIIb or IV platinum-refractory non-small-cell lung cancer were treated with 100 mg/m2 of docetaxel intravenously over 1 hour every 3 weeks. The responses of 42 of 44 patients were assessable. Most patients had a Zubrod performance status of 1; the predominant histologic type was adenocarcinoma (61%), and 91% of patients had stage IV disease. RESULTS: Nine of 42 assessable patients (21%) achieved a partial response to treatment. The median response duration (from response to progression) was 17 weeks, and the projected median survival duration of all patients is 42 weeks (51 weeks for adenocarcinoma and 22 weeks for nonadenocarcinoma). Grade 3/4 neutropenia occurred in 85% of patients and was associated with fever that required intravenous antibiotics in 16% of patients (3% of cycles). Other acute side effects included easily treated hypersensitivity reactions and dermatitis. Cumulative side effects included fluid retention and neuropathy. CONCLUSION: Docetaxel administered at 100 mg/m2 intravenously every 3 weeks has notable activity against platinum-refractory non small-cell lung cancer, with a 21% major response rate. Primary side effects were neutropenia, hypersensitivity, and fluid retention. PMID- 7884426 TI - Teniposide for brain metastases of small-cell lung cancer: a phase II study. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. AB - PURPOSE: Here we report the results of a phase II study of teniposide, one of the most active drugs against small-cell lung cancer (SCLC), in patients with brain metastases. PATIENTS AND METHODS: Patients with SCLC who presented with brain metastases at diagnosis (n = 11) or during follow-up evaluation after treatment (n = 69) were treated with teniposide at a dose of 150 mg/m2 intravenously on days 1, 3, and 5 at 3-week intervals in an outpatient setting. Response in the brain was evaluated by brain computed tomography (CT) after two, six, and 12 courses. RESULTS: In 26 of 80 assessable patients, an intracranial response was seen, with a response rate of 33% (95% confidence interval, 22% to 44%). The median response duration was 5.4 months for patients with a complete response (CR) and 4.2 months for patients with a partial response (PR). Patients who required corticosteroids for peritumoral edema had a significantly lower response rate than patients who did not receive corticosteroids. Neurologic function at the start of treatment had a significant influence (neurologic function 1 better than 2, respectively, better than 3 and 4; P < .001), as did the number of cycles of previous chemotherapy (0 better than 1 to 5 cycles, respectively, better than > 5 cycles; P = .043). Grade 3/4 leukocytopenia and thrombocytopenia were seen in 3% and 39%, respectively, of 80 patients. Toxicity-related death was seen in eight patients, seven of whom were previously treated with chemotherapy. CONCLUSION: Teniposide is active against brain metastases of SCLC. It is a suitable drug for palliation, especially of patients without extensive pretreatment and with a good neurologic function and performance status. Patients previously treated with cranial radiotherapy are also candidates for this therapy. If systemic chemotherapy is considered for tumor progression outside the brain, radiotherapy of brain metastases might be omitted or delayed pending the effect of chemotherapy. The use of corticosteroids in patients with brain metastases treated with chemotherapy might influence the efficacy of the chemotherapy. PMID- 7884427 TI - Treatment outcome and prognostic factors for primary nasal lymphoma. AB - PURPOSE: To report our experience managing a large series of Chinese patients with primary nasal lymphoma. PATIENTS AND METHODS: From January 1975 to December 1993, 100 patients (median age, 50 years) with newly diagnosed primary nasal lymphoma were studied. There were four low-grade, 62 intermediate-grade, nine high-grade, and 25 unclassifiable lymphomas. Immunophenotyping was performed in 45 patients: eight B cell, 35 T cell, and two uncertain. All cases of angiocentric lymphoma that were typed were T cell. Fifty-two patients had stage I disease, 15 had stage II, four had stage III, and 29 had stage IV. Only 15 patients had B symptoms (weight loss, night sweats, and/or fever), and 11 had bulky disease. Thirty-nine patients with clinically localized stage I and II disease received local radiotherapy alone (before 1980), and the remaining 28 stage I and II patients received combination chemotherapy followed by local radiotherapy. The 33 patients with advanced stage III and IV disease were given combination chemotherapy, and additional radiotherapy was given to five of them who had bulky local disease. RESULTS: Significantly higher complete remission rates were observed in patients with early stages of disease and those without B symptoms. Superior disease-free survival after complete remission was observed in patients with stage I/II disease. Univariate factors associated with a better overall survival included age less than 60 years, stage I disease, and absence of B symptoms. Survival was significantly better in the subgroup of patients with stage I disease. CONCLUSION: Patients with nasal lymphoma, especially those with advanced disease, seemed to have a poor prognosis, and their clinical outcome was not improved significantly by the use of chemotherapy instead of radiotherapy or the use of doxorubicin-containing chemotherapeutic regimens. PMID- 7884428 TI - Organ-function preservation in advanced oropharynx cancer: results with induction chemotherapy and radiation. AB - PURPOSE: To evaluate the feasibility and efficacy of a strategy using induction chemotherapy followed by radiation therapy (RT) as a means of organ-function preservation in patients with advanced oropharynx cancer. PATIENTS AND METHODS: From January 1983 to December 1990, 33 patients with advanced squamous cell oropharynx cancer whose appropriate surgical management would have required a tongue procedure and potential total laryngectomy were treated with one to three cycles of cisplatin (CDDP)-based induction chemotherapy. Patients with a complete response (CR) or partial response (PR) at the primary site then received definitive external-beam RT with or without interstitial implant with or without neck dissection with surgery to the primary tumor site reserved for disease persistence or relapse; patients with less than a PR after chemotherapy had appropriate surgery and postoperative RT recommended. RESULTS: With a median follow-up period of 6.2 years, actuarial overall and failure-free survival rates at 5 years are 41% and 42%, respectively. Chemotherapy toxicity contributed to the death of two patients and was possibly a factor in two others. Local control was achieved in 14 patients (42%) without any surgery to the larynx or tongue. Among 13 patients currently alive, all had a preserved larynx and only one required tongue surgery; 12 of 13 have speech subjectively described as always understandable; and nine of 13 have no significant restrictions in their diet. CONCLUSION: This treatment program is feasible and effective in patients with advanced oropharynx cancer and produces an excellent functional outcome in most long-term survivors. Modifications to optimize patient selection, minimize toxicity, and improve local control are indicated. The relative toxicity, efficacy, and functional outcome provided by this and other chemotherapy and RT programs versus either standard surgery and/or RT options can only be addressed in a randomized comparison of these therapies. PMID- 7884429 TI - Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. AB - PURPOSE: To determine the efficacy and toxicity of a high-dose interleukin-2 (IL 2) regimen in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: Two hundred fifty-five assessable patients were entered onto seven phase II clinical trials. Proleukin (aldesleukin; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous (i.v.) infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical cycle of treatment was scheduled following 5 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. RESULTS: The overall objective response rate was 14% (90% confidence interval [CI], 10% to 19%), with 12 (5%) complete responses (CRs) and 24 (9%) partial responses (PRs). Responses occurred in all sites of disease, including bone, intact primary tumors, and visceral metastases, and in patients with large tumor burdens or bulky individual lesions. The median response duration for patients who achieved a CR has not been reached, but was 19.0 months for those who achieved a PR. Baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was the only predictive prognostic factor for response to IL-2. While treatment was associated with severe acute toxicities, these generally reversed rapidly after therapy was completed. However, 4% of patients died of adverse events judged to be possibly or probably treatment-related. CONCLUSION: High-dose IL-2 appears to benefit some patients with metastatic renal cell carcinoma by producing durable CRs or PRs. Despite severe acute treatment-associated toxicities, IL-2 should be considered for initial therapy of patients with appropriately selected metastatic renal cell carcinoma. PMID- 7884430 TI - Biologic and clinicopathologic factors as indicators of specific relapse types in node-negative breast cancer. AB - PURPOSE AND METHODS: We evaluated, in 1,800 patients with node-negative tumors treated with locoregional therapy until relapse, the competitive risks for different types of metastasis by cell proliferation (3H-thymidine labeling index [3H-dT LI]), estrogen receptors (ERs), and progesterone receptors (PgRs), and by the integration of biologic and clinicopathologic information. RESULTS: Hormone receptor status and proliferative activity of the primary tumor were not indicative of contralateral failures. Hormone receptors failed to predict the 8 year incidence of locoregional recurrence, but they were significant indicators of distant metastasis and overall survival. The latter finding was confirmed even in multivariate analysis. Conversely, cell proliferation predicted both locoregional and distant metastases and survival, regardless of patient age, tumor size, and ER and PgR status. Recursive partitioning and amalgamation analysis ascribed to cell proliferation an important prognostic role for locoregional recurrence together with patient age and tumor size. CONCLUSION: Biologic markers, in particular cell proliferation, provide information for the different types of relapse and could complement the predictive role of pathologic staging. PMID- 7884431 TI - Improved control of invasive cervical cancer in Sweden over six decades by earlier clinical detection and better treatment. AB - PURPOSE: Cancer of the cervix uteri can be controlled by cytologic screening for the detection of precursor lesions, but such intervention remains unrealistic in many countries in which this cancer is common. The possibility of reducing mortality by earlier clinical detection, followed by basic therapy, has never been properly assessed. PATIENTS AND METHODS: We compiled records of incident cases of invasive cancer of the cervix diagnosed in a defined area of Sweden from 1930 through 1990. In a cohort of 6,044 women, we analyzed temporal trends in incidence and survival by clinical stage and age at diagnosis. Generalized proportional hazards models were used to study several factors simultaneously and quantify the overall reduction in mortality. RESULTS: For each successive stage at diagnosis, the overall risk of dying increased 2.5-fold (95% confidence interval [CI], 2.4 to 2.7). From 1930, a marked improvement in stage distribution was accompanied by increasing survival rates in stages I and II disease. These changes largely took place before the introduction of screening and external-beam radiation. The 10-year relative survival rate increased from 33% in the 1930s to approximately 55% in the 1950s and thereafter. CONCLUSION: Improvements in public and professional awareness of cervical cancer resulted in diagnoses at earlier clinical stages. The rate of cure in early stages improved when basic local treatment was introduced, but only little of the progress was attributable to the introduction of more advanced treatment technologies. These findings offer considerable hope for a substantial reduction in the mortality of cervical cancer without cytologic screening, even in countries with limited resources. PMID- 7884432 TI - Impact of doxorubicin on survival in advanced ovarian cancer. AB - PURPOSE: Our study examined the impact of the addition of doxorubicin to ovarian cancer regimens in general, while removing the confounding influence of other drugs. MATERIALS AND METHODS: We performed an overview using the data from two large analyses, the Advanced Ovarian Cancer Trialists Group (AOCTG [Br Med J 303:884-893, 1991] and Williams et al [Seminars in Oncol 19:120-128, 1992 (suppl 2)]) and the Ovarian Cancer Meta-Analysis Project (OCMP [J Clin Oncol 9:1668 1674, 1991]). RESULTS: Our data suggest that the addition of doxorubicin significantly improves survival (hazards ratio, 0.85; 95% confidence interval [CI], 0.76 to 0.95; P = .003) and that the size of this benefit is of a similar magnitude to that of platinum. CONCLUSION: The implication of our results is that the basic drugs for the standard treatment of advanced ovarian should be a combination of platinum and doxorubicin. The addition of an alkylating agent may add toxicity and lead to a dose reduction of these two drugs. In view of recent data on combination therapy with paclitaxel and platinum, it would be appropriate to compare this regimen with a combination of doxorubicin and platinum. PMID- 7884433 TI - Recombinant human interleukin-3 to dose-intensify carboplatin and cyclophosphamide chemotherapy in epithelial ovarian cancer: a phase I trial. AB - PURPOSE: To define the optimal dose of recombinant human interleukin-3 (rhIL-3) required to intensify the dose of carboplatin and cyclophosphamide for advanced epithelial ovarian cancer. PATIENTS AND METHODS: Seventeen patients were treated on day 1 with carboplatin (dose adjusted for creatinine clearance: range, 257 to 385 mg/m2; median, 300 mg/m2) and cyclophosphamide (750 mg/m2). rhIL-3 5 micrograms/kg/d (n = 10) or 10 micrograms/kg/d (n = 7) was administered subcutaneously (SC) on days 2 through 11. Carboplatin dose was escalated if no postponement of cycles 1 to 3 had occurred. RESULTS: A 3-week interval was achieved in 62% of cycles and a 4-week interval in 81%, with no difference between the rhIL-3 doses. A neutrophil nadir less than 0.5 x 10(9)/L occurred in 35% of the cycles at 5 micrograms/kg/d and in 52% at 10 micrograms/kg/d of rhIL-3 (nonsignificant difference). The mean platelet nadir in cycle 1 was 173 +/- 78 x 10(9)/L at 5 micrograms/kg/d and 340 +/- 152 x 10(9)/L at 10 micrograms/kg/d of rhIL-3 (P < .05), with a faster recovery of platelets at 10 micrograms/kg/d (P < .05). Progressive myelotoxicity occurred for leukocytes and platelets at both rhIL-3 doses and required chemotherapy postponement in later cycles. The planned six cycles were completed by 41% of patients. Fever (> or = 38.5 degrees C) occurred in 38% of cycles at 5 micrograms/kg/d and in 97% at 10 micrograms/kg/d (P < .0005); headache and myalgias occurred in 30% and 44%, respectively. After two cycles, diffuse erythema, facial edema, and urticaria were observed in two patients at 5 micrograms/kg/d and in five patients at 10 micrograms/kg/d of rhIL 3. This resolved after discontinuation of rhIL-3 and administration of corticosteroids and antihistamines. CONCLUSION: A dose of 5 micrograms/kg/d of rhIL-3 proved to be optimal to intensify the carboplatin and cyclophosphamide regimen. It permitted the administration of carboplatin and cyclophosphamide combination therapy every 3 weeks in 62% of cycles. PMID- 7884434 TI - Population pharmacodynamic study of amonafide: a Cancer and Leukemia Group B study. AB - PURPOSE: To determine if variability in toxicity of amonafide during phase II trials could be correlated with pharmacokinetic variability. PATIENTS AND METHODS: Seventy-three patients enrolled onto three Cancer and Leukemia Group B (CALGB) phase II trials of amonafide (300 mg/m2 daily for 5 days) were studied, using a limited sampling strategy (45 minutes and 24 hours) to estimate the amonafide area under the plasma concentration-time curve (AUC). Concentrations of N-acetyl-amonafide, an active metabolite, were also determined. RESULTS: The primary determinant of toxicity at a fixed dose of amonafide was the extent of N acetylation. Fast acetylators (36% of patients) had significantly greater toxicity than slow acetylators (64% of patients), with median WBC nadirs of 500/microL and 3,400/microL, respectively (P < or = .001). In a multivariate analysis, lower pretreatment WBC count, lower albumin level, and nonwhite race were also independently associated with toxicity. Further analysis of interracial differences demonstrated that minority women had slower clearance of amonafide (P = .026) and a higher incidence of grade 4 leukopenia (P = .042). CONCLUSION: The highly variable toxicity of amonafide is primarily due to genetic differences in N-acetylation. Other genetic (race) and acquired factors (baseline WBC count and albumin level) also appear to influence the extent of toxicity observed following administration of this agent. PMID- 7884435 TI - Pain and depression in patients with newly diagnosed pancreas cancer. AB - PURPOSE: To evaluate the prevalence of pain and depression, their correlation, and their effect on quality of life in patients with recently diagnosed adenocarcinoma of the pancreas (PC). MATERIALS AND METHODS: Cross-sectional pain and psychosocial distress were assessed using validated instruments, including the Memorial Pain Assessment Card (MPAC), Beck Depression Inventory (BDI), Hopelessness Scale (BHS), and Functional Living Index-Cancer (FLIC). Patients were evaluated before their first operation for PC or first treatment with chemotherapy at a large tertiary-care cancer center. RESULTS: One hundred thirty patients with proven PC were studied: 83 before their operation and 47 before their first chemotherapy treatment. At the time of study entrance, 37% of patients had no pain and an additional 34% had pain that was mild or less severe. Only 29% of patients had moderate, strong, or severe pain. Chemotherapy patients reported significantly more intense pain than did preoperative patients (P = .02). Symptoms of depression were assessed using the BDI and BHS scales. A substantial minority of patients (38%) had BDI scores > or = 15, which suggests high levels of depressive symptoms. There was a significant correlation between increasing pain and depressive symptoms among those who experienced pain. Quality of life was assessed using the Weekly Activity Checklist (WAC) and the FLIC. Compared with patients who had no pain or mild pain, patients with moderate or greater pain had significantly impaired functional activity (P = .03) and poorer quality-of-life scores (P = .02) when compared with those with lesser degrees of pain. There were significant correlations between increasing pain and depression and between pain and depressive symptoms and impaired quality of life and function. CONCLUSION: Our results indicate that moderate or severe pain and symptoms of depression are not as prevalent in recently diagnosed PC patients as is generally believed. However, one third have inadequate pain control despite the use of oral analgesics. These patients can be identified by the use of a simple self-report instrument (the MPAC card). Quality of life and function are adversely affected by moderate or greater levels of perceived pain intensity. A simple and rapid assessment is possible and can identify high-risk patients in need of intervention that may improve quality of life. PMID- 7884436 TI - Ovarian cancer screening. AB - PURPOSE: To review potential screening tools of early ovarian cancer and the associated risk factors for the development of ovarian carcinoma. DESIGN AND RESULTS: A review of pertinent literature was conducted, restricted to English language published reports, book chapters, and articles. The value of serum tumor markers, particularly CA 125, ultrasound, transabdominal and transvaginal ultrasonography, and transvaginal color Doppler imaging as screening tools for ovarian cancer was assessed. CONCLUSION: Based on the literature, a large-scale long-term study that compares the mortality rates of a screened versus unscreened patient population is required before the efficacy of any screening method can be determined definitively. PMID- 7884437 TI - Combination chemotherapy with tetracycline and aggressive supportive care for immunoproliferative small-intestinal disease lymphoma. PMID- 7884438 TI - Polymerase chain reaction monitoring for bcl-2 can be a dependable test under the right conditions. PMID- 7884439 TI - Combination chemotherapy of metastatic melanoma. PMID- 7884440 TI - Effect of flutamide withdrawal on response assessment of estramustine and etoposide for prostate cancer. PMID- 7884441 TI - The price of success. PMID- 7884442 TI - Radiotherapy still has a major role in the management of localized orbital rhabdomyosarcoma. PMID- 7884443 TI - Reviving the pelvic examination for evaluating the status of ovarian carcinoma. PMID- 7884444 TI - Dynamic coupling among neocortical neurons during evoked and spontaneous spike wave seizure activity. AB - 1. We investigated the development from patterns of electroencephalogram (EEG) synchronization to paroxysms consisting of spike-wave (SW) complexes at 2-4 Hz or to seizures at higher frequencies (7-15 Hz). We used multisite, simultaneous EEG, extracellular, and intracellular recordings from various neocortical areas and thalamic nuclei of anesthetized cats. 2. The seizures were observed in 25% of experimental animals, all maintained under ketamine and xylazine anesthesia, and were either induced by thalamocortical volleys and photic stimulation or occurred spontaneously. Out of unit and field potential recordings within 370 cortical and 65 thalamic sites, paroxysmal events occurred in 70 cortical and 8 thalamic sites (approximately 18% and 12%, respectively), within which a total of 181 neurons (143 extracellular and 38 intracellular) were simultaneously recorded in various combinations of cell groups. 3. Stimulus-elicited and spontaneous SW seizures at 2-4 Hz lasted for 15-35 s and consisted of barrages of action potentials related to the spiky depth-negative (surface-positive) field potentials, followed by neuronal silence during the depth-positive wave component of SW complexes. The duration of inhibitory periods progressively increased during the seizure, at the expense of the phasic excitatory phases. 4. Intracellular recordings showed that, during such paroxysms, cortical neurons displayed a tonic depolarization (approximately 10-20 mV), sculptured by rhythmic hyperpolarizations. 5. In all cases, measures of synchrony demonstrated time lags between discharges of simultaneously recorded cortical neurons, from as short as 3-10 ms up to 50 ms or even longer intervals. Synchrony was assessed by cross-correlograms, by a method termed first-spike-analysis designed to detect dynamic temporal relations between neurons and relying on the detection of the first action potential in a spike train, and by a method termed sequential-field-correlation that analyzed the time course of field potentials simultaneously recorded from different cortical areas. 6. The degree of synchrony progressively increased from preseizure sleep patterns to the early stage of the SW seizure and, further, to its late stage. In some cases the time relation between neurons during the early stages of seizures was inversed during late stages. 7. These data show that, although the common definition of SW seizures, regarded as suddenly generalized and bilaterally synchronous activities, may be valid at the macroscopic EEG level, cortical neurons display time lags between their rhythmic spike trains, progressively increased synchrony, and changes in the temporal relations between their discharges during the paroxysms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884445 TI - Motor cortical activity during voluntary gait modifications in the cat. II. Cells related to the hindlimbs. AB - 1. To determine whether the motor cortex is involved in the modification of the hindlimb trajectory during voluntary adjustments of the locomotor cycle, we recorded the discharge patterns of 72 identified pyramidal tract neurons (PTNs) within the hindlimb region of pericruciate area 4 during a task in which cats stepped over obstacles attached to a moving treadmill belt. Data were also recorded from representative flexor and extensor muscles of the fore- and hindlimbs contralateral to the recording site. 2. To step over the obstacles, the cats increased flexion sequentially at the knee, ankle, and then the hip to bring the leg above and over the obstacle. This flexion movement was followed by a strong extension of the whole limb that repositioned the foot on the treadmill belt. These changes in limb trajectory were associated with large changes in the level of the activity of many flexor and extensor muscles of the hindlimb, and especially of the knee flexor, semitendinosus. On the basis of the time of onset of the knee and ankle extensor muscles in those steps when the limb was the first to be brought over the obstacle, the swing phase of the modified step cycle was subdivided into two parts, Phase I and Phase II, which correspond respectively to the flexion of the limb (F) and the initial extension (E1). 3. The temporal sequence of the movement was the same whether the hindlimb was the first (lead) or second (trail) to step over the obstacle, although the relative time between flexion at the three joints was changed in the two conditions. 4. Seventy-two PTNs were recorded from the posterior bank of the cruciate sulcus during the voluntary gait modifications. Sixty-three (63/72) of these PTNs had receptive fields that were confined to the contralateral hindlimb, or were recorded from penetrations in which such cells were found. Nine (9/72) PTNs had receptive fields on both the contralateral fore- and hindlimbs. Microstimulation applied through the recording electrode evoked, in all cases, brief twitch responses only in contralateral hindlimb musculature. 5. Forty-two (42/63) of those PTNs with receptive fields confined to the hindlimb showed a significant increase in their discharge frequency when the limb contralateral to the recording site was the first to step over the obstacle (lead limb). Twenty-nine PTNs (29/63) discharged maximally during the swing phase (18 in Phase I and 11 in Phase II), including two PTNS that also increased their discharge frequency during stance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884446 TI - Effects of conditioning cutaneomuscular stimulation on the soleus H-reflex in normal and spastic paretic subjects during walking and standing. AB - 1. The modulation of the soleus H-reflex by a conditioning cutaneomuscular stimulation was investigated in 10 normal and 10 spastic paretic subjects who suffered from incomplete spinal cord lesions. The different motor tasks examined were standing, locomotion, and the maintenance of static limb postures to mimic critical gait events. The test soleus H-reflex was obtained by stimulating the tibial nerve in the popliteal fossa with a single 1-ms pulse at an intensity that produced a barely detectable M wave. The conditioning stimulus, consisting of an 11-ms train of three 1-ms pulses at 200 Hz, was delivered to the ipsilateral medial plantar arch, stimulating predominantly the medial plantar nerve, at an innocuous intensity of 2.5-3.0 X sensory threshold and at a conditioning-test delay of 45 ms. 2. During quiet standing, the H-reflex amplitude was inhibited only marginally by the conditioning cutaneomuscular stimulation, not reaching statistical significance in either the normal or spastic group of subjects. Although there was a trend of reflex inhibition in the normal subjects as the conditioning intensity was increased, a reversed trend of reflex facilitation was observed in the spastic patients. 3. During treadmill walking, the conditioned H reflex was inhibited significantly during all phases in all the normal subjects and in one mildly impaired patient. In the moderately and severely impaired patients, cutaneomuscular stimulation selectively inhibited the soleus H-reflex in the early stance and swing phases, thereby producing a near normal phasic modulation pattern. Such modulatory effects were not present under static gait mimicking conditions. 4. The task-specific and phase-dependent effects of cutaneomuscular stimulation on the soleus H-reflex in the spinal cord-injured patients revealed strong inhibitory influence on Ia afferents from cutaneomuscular inputs. It is plausible that inhibition occurs at both pre- and postsynaptic levels. 5. It is concluded that normal Ia modulatory mechanisms during locomotion are deficient in spastic spinal cord-injured patients and can partially and artificially be restored by cutaneomuscular stimulation applied to the sole of the foot. This can be used as a functional electrical stimulation (FES) regime in gait rehabilitation. PMID- 7884447 TI - Global synchronous response to autogenous song in zebra finch HVc. AB - 1. The spatial distribution of neuronal responses to autogenous song (AS) was investigated in the HVc of urethan-anesthetized adult male zebra finches (Taeniopygia guttata). In seven birds, penetrations covered the entire mediolateral, rostrocaudal, or dorsoventral extents of HVc. In an eighth, control birth penetrations were made near to but outside of HVc. Reconstruction of recording sites from histological material indicated a good correspondence between sites that exhibited stronger responses to AS than to tone or noise bursts, and sites that were within HVc. 2. Within each experimental bird but not in the control, multiple-unit responses to AS were similar across the entire spatial extent of HVc (up to 1.3 mm). For each experimental bird, the strongest responses occurred within a narrow range of times. The middle of this range of times is called the time of maximum synchronization (TMS). Across birds, 34-75% of recording sites exhibited the same TMS. With the use of a criterion of > 33% of sites exhibiting their strongest responses at the TMS, the temporal scatter around the TMS varied between 6 and 138 ms across individuals. In six of the seven experimental birds, the position of the TMS was not affected by changing the window of integration from 10 to 150 ms. In two experimental birds, short windows of integration tended to emphasize beginning portions of the song. In one case this effect was sufficiently strong to change the TMS for short windows of integration. 3. Each TMS was associated with a syllable of maximum synchronization (SMS). The positions of the SMS varied considerably across birds. In four birds the SMS was one of the syllables of the first motif (a motif is a temporal sequence of syllables that can be repeated > or = 1 times to form a song), in two birds the SMS was the introductory note of song, and in one bird the SMS was the second syllable of the last (3rd) motif. Syllables of the same type as the SMS but occurring in other motifs typically elicited much weaker responses, in many cases weaker than other syllables in those motifs. Syllables that elicited strong responses in non-SMS motifs did not necessarily elicit strong responses in the SMS motif, even if they preceded the SMS. There were no apparent acoustical features of the SMS or the preceding syllable that could account for the global synchronous response to song.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884448 TI - Inhibitory inputs modulate discharge rate within frequency receptive fields of anteroventral cochlear nucleus neurons. AB - 1. The amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glycine function as inhibitory neurotransmitters associated with nonprimary inputs onto spherical bushy and stellate cells, two principal cell types located in the anteroventral cochlear nucleus (AVCN). These neurons are characterized by primary like (including phase-locked) and chopper temporal response patterns, respectively. 2. Inhibition directly adjacent to the excitatory response area has been hypothesized to sharpen or limit the breadth of the tonal frequency receptive field. This study was undertaken to test whether GABA and glycine circuits function primarily to sharpen the lateral edges of the tonal excitatory response area or to modulate discharge rate within central portions of the excitatory response area of AVCN neurons. 3. To test this, iontophoretic application of the glycineI antagonist, strychnine, or the GABAA antagonist, bicuculline, was used to block inhibitory inputs after obtaining control families of isointensity contours (response areas) from extracellularly recorded AVCN neurons. 4. Blockade of GABA and/or glycine inputs was found to increase discharge rate primarily within the excitatory response area of neurons displaying chopper and primary-like temporal responses with little or no change in bandwidth or in off-characteristic frequency (CF) discharge rate. 5. The principal sources of inhibitory inputs onto AVCN neurons are cells located in the dorsal cochlear nucleus and superior olivary complex, which appear to be tonotopically matched to their targets. In agreement with these morphological studies, the data presented in this paper suggest that most GABA and/or glycine inhibition is tonotopically aligned with excitatory inputs. 6. These findings support models that suggest that GABA and/or glycine inputs onto AVCN neurons are involved in circuits that adjust gain to enable the detection of signals in noise by enhancing signal relative to background. PMID- 7884449 TI - Envelope-responsive neurons in areas 17 and 18 of cat. AB - 1. Single cortical neurons are known to respond to visual stimuli containing Fourier components only in a narrow range of spatial frequencies. This investigation demonstrates that some neurons in cat area 17 and 18 can also respond to certain stimuli that have no Fourier components inside the cell's luminance spatial frequency passband. 2. To study such "non-Fourier" responses, we used envelope stimuli that consisted of a high-spatial-frequency sinusoidal luminance grating (carrier) whose contrast was modulated by a low-spatial frequency sine wave (envelope). There was no Fourier component at the apparent periodicity of the envelope spatial frequency. However, some cells responded to such a "phantom" component of the envelope modulation when it fell inside the cell's luminance spatial frequency passband while all the real Fourier components in the stimuli were outside. 3. We conducted extensive control experiments to eliminate the possibility of producing artifactual responses to the envelope stimuli due to any small residual nonlinearity of the z-linearized CRT screen. The control experiments included 1) testing of screen linearity to ensure that the effect from the residual screen nonlinearity was no larger than the sensitivity level of visual responses and 2) comparing the responses to envelope stimuli with the responses to the equivalent contrast of the artifact produced by the screen nonlinearity. All these control experiments indicated that any effect of screen nonlinearity did not contribute significantly to the neural envelope responses. 4. We performed a statistical analysis to obtain an index of relative strength of envelope responses for each cell and to objectively classify cells as "envelope-responsive" or "non-envelope-responsive."(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884450 TI - Population encoding of spatial frequency, orientation, and color in macaque V1. AB - 1. We recorded local field potentials in the parafoveal representation in the primary visual cortex of anesthetized and paralyzed macaque monkeys with a multicontact electrode that provided for sampling of neural activity at 16 sites along a vertical penetration. Differential recordings at adjacent contacts were transformed into an estimate of current source density (CSD), to provide a measure of local neural activity. 2. We used m-sequence stimuli to map the region of visual space that provided input to the recording site. The local field potential recorded in macaque V1 has a population receptive field (PRF) size of approximately 2 deg2. 3. We assessed spatial tuning by the responses to two dimensional Gaussian noise, spatially filtered to retain power only within one octave. Responses to achromatic band-limited noise stimuli revealed a prominent band-pass spatial tuning in the upper layers, but a more low-pass spatial tuning in lower layers. 4. We assessed orientation tuning by the responses to band limited noise whose spectrum was further restricted to lie within 45 degrees wedges. The local field potential showed evidence of orientation tuning at most sites. Orientation tuning in upper and lower layers was manifest by systematic variations not only in response size but also in response dynamics. 5. We assessed chromatic tuning by the responses to isotropic band-limited noise modulated in a variety of directions in tristimulus space. Some lower-layer locations showed a nulling of response under near-isoluminant conditions. However, response dynamics in upper and lower layers depended not only on luminance contrast, but also on chromatic inputs. 6. Responses to near isoluminant stimuli and to low-contrast luminance modulation were shifted to lower spatial frequencies. 7. We determined the extent to which various temporal frequencies in the response conveyed information concerning spatial frequency, orientation, and color under the steady-state conditions used in these studies. In each case, information is distributed in the response dynamics across a broad temporal frequency range, beginning at 4 Hz (the lowest frequency used). For spatial frequency the information rate remains significant up to at least 25 Hz. For orientation tuning and chromatic tuning, the information rate is lower overall and remains significant up to 13 Hz. In contrast, for texture discrimination, information is shifted to lower temporal frequencies. PMID- 7884451 TI - Evidence from simultaneous intracellular recordings in rat hippocampal slices that area CA3 pyramidal cells innervate dentate hilar mossy cells. AB - 1. Simultaneous intracellular recordings of area CA3 pyramidal cells and dentate hilar "mossy" cells were made in rat hippocampal slices to test the hypothesis that area CA3 pyramidal cells excite mossy cells monosynaptically. Mossy cells and pyramidal cells were differentiated by location and electrophysiological characteristics. When cells were impaled near the border of area CA3 and the hilus, their identity was confirmed morphologically after injection of the marker Neurobiotin. 2. Evidence for monosynaptic excitation of a mossy cell by a pyramidal cell was obtained in 7 of 481 (1.4%) paired recordings. In these cases, a pyramidal cell action potential was followed immediately by a 0.40 to 6.75 (mean, 2.26) mV depolarization in the simultaneously recorded mossy cell (mossy cell membrane potentials, -60 to -70 mV). Given that pyramidal cells used an excitatory amino acid as a neurotransmitter (Cotman and Nadler 1987; Ottersen and Storm-Mathisen 1987) and recordings were made in the presence of the GABAA receptor antagonist bicuculline (25 microM), it is likely that the depolarizations were unitary excitatory postsynaptic potentials (EPSPs). 3. Unitary EPSPs of mossy cells were prone to apparent "failure." The probability of failure was extremely high (up to 0.72; mean = 0.48) if the effects of all presynaptic action potentials were examined, including action potentials triggered inadvertently during other spontaneous EPSPs of the mossy cell. Probability of failure was relatively low (as low as 0; mean = 0.24) if action potentials that occurred during spontaneous activity of the mossy cell were excluded. These data suggest that unitary EPSPs produced by pyramidal cells are strongly affected by concurrent synaptic inputs to the mossy cell. 4. Unitary EPSPs were not clearly affected by manipulation of the mossy cell's membrane potential. This is consistent with the recent report that area CA3 pyramidal cells innervate distal dendrites of mossy cells (Kunkel et al. 1993). Such a distal location also may contribute to the high incidence of apparent failures. 5. Characteristics of unitary EPSPs generated by pyramidal cells were compared with the properties of the unitary EPSPs produced by granule cells. In two slices, pyramidal cell and granule cell inputs to the same mossy cell were compared. In other slices, inputs to different mossy cells were compared. In all experiments, unitary EPSPs produced by granule cells were larger in amplitude but similar in time course to unitary EPSPs produced by pyramidal cells. Probability of failure was lower and paired-pulse facilitation more common among EPSPs triggered by granule cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884452 TI - FRF peptides in the ARC neuromuscular system of Aplysia: purification and physiological actions. AB - 1. One preparation that has proven to be advantageous for the study of neuromuscular modulation is the accessory radula closer (ARC) muscle of Aplysia californica and its motor neurons B15 and B16. In this study three members of a new peptide family have been purified from this well-characterized preparation. Because these peptides terminate in Phe-Arg-Phe-amide, we have named them FRFA, FRFB, and FRFC. The FRFs are thus RFamide peptides and are related to the widely studied neuropeptide FMRFamide. 2. The FRFs are present in the ARC motor neuron B15 in small quantities. 3. When they are exogenously applied, the FRFs decrease the size of ARC muscle contractions elicited by stimulation of either motor neuron B15 or B16. They appear to do this by a combination of presynaptic and postsynaptic actions. 4. Presynaptically, the FRFs appear to act like the buccalins, another family of inhibitory ARC neuropeptides. Both families of peptides reduce the size of motor neuron-elicited excitatory junction potentials (EJPs) presumably by decreasing presynaptic acetylcholine (ACh) release. 5. Postsynaptically, the FRFs appear to depress contractions because they activate a characteristic voltage-dependent, 4-amino-pyridine-sensitive K current in the ARC muscle. The same current is activated by a second class of ARC modulators: those that exert potentiating actions at low doses and inhibitory actions at high doses, i.e., serotonin, the small cardioactive peptides (SCPs), and particularly the myomodulins. Receptors mediating activation of the K current by the FRFs and the other modulators do, however, appear to be different. 6. We hypothesize that the inhibitory actions of the FRFs prevent excessively large muscle contractions. If contraction size is limited, then contraction duration is also limited. This may allow faster and more energetically favorable switching between contractions of antagonistic muscles. PMID- 7884453 TI - Calcium current and inactivation in identified neurons in Hermissenda crassicornis. AB - 1. N-type (omega-conotoxin sensitive) calcium currents (ICa) were recorded in identified neurons in Hermissenda crassicornis using low-resistance patch electrodes (0.7 +/- 0.3 M omega; n = 101) under conditions that eliminated inward Na+ currents (choline ions substitution) and suppressed outward K+ currents (Cs+, tetraethylammonium, and 4-AP). Step depolarization from a holding potential of 60 mV to potentials above -30 mV elicited ICa, which peaked approximately 20 mV and declined with increasing depolarizations. 2. Evidence for a low-threshold current was present. Step depolarization from a more hyperpolarizing potentials (e.g., -90 mV) revealed a small shoulder (< 100 pA) at -60 to -40 mV that was sensitive to Co2+ and Ni2+. However, under the conditions examined here (holding potential of -60 mV), the high-voltage-activated current predominated. 3. Barium (Ba2+) and strontium (Sr2+) permeate the Ca2+ channel with similar activation kinetics (ease of permeation; Ba2+ > Ca2+ > Sr2+). Steady-state activation of permeability versus membrane potentials for Ca2+, Ba2+, and Sr2+ as charge carriers could be fitted with the Boltzmann equation, with half-activation voltage and slope factor of 2.9 and 7.7 mV for ICa, -13.1 mV and 7.8 for Ba2+ current (IBa) and -2.3 mV and 7.8 for Sr2+ current (ISr). The time course of activation was monotonic with time constant (tau) for ICa ranging from 2 to 8 ms. 4. The inactivation profile was complex. At negative step potentials (e.g., -20 mV), inactivation of the current was slow. Depolarization steps to relatively positive voltages (e.g., 10 mV) showed more rapid inactivation than those at more positive potentials (e.g., 40 mV). When extracellular Ca2+ was raised from 5 to 10 mM, a biphasic decay (tau fast of 25 +/- 4 ms; and tau slow of 473 +/- 64 ms; mean +/- SD, n = 9) was seen. Such an observation suggested a current-mediated inactivation. 5. With a pulse duration of approximately 350 ms, ISr showed inactivation whereas Ba2+ virtually removed the decay. However, IBa turned off with more prolonged depolarization. 6. A twin-pulse protocol was used to assess the voltage dependence of inactivation: an incomplete U-shaped inactivation curve was observed for ICa, IBa, and ISr. Channels available for inactivation were increased in the presence of Ca2+ ions. 7. Inactivation was further studied with the Ca2+ chelators, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N' tetraacetic acid and bis(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA). With 10 mM of BAPTA, in the pipette, inactivation was reduced but not removed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884454 TI - Phase-locked response characteristics of single neurons in the frog "cochlear nucleus" to steady-state and sinusoidal-amplitude-modulated tones. AB - 1. We made extracellular recordings from 164 single neurons in the frog dorsal medullary nucleus (DMN), a homologue of the cochlear nucleus. Phase-locked responses to tones at the unit's characteristic frequency (CF) and to off-CF tones were evaluated. We also stimulated units with tones at CF that were amplitude modulated sinusoidally between 5 and 1,000 Hz and examined responses to these stimuli. 2. Results showed that single neurons in the frog DMN displayed phase-locked discharges to tones at frequencies < or = 800 Hz. Phase-locking was robust at low frequencies (< 400 Hz) and became poorer at higher frequencies; the variation of the synchronization coefficient (SC) with frequency typically showed a low-pass characteristic. 3. The capacity of phase-locking to tones was correlated with the functional classification of a DMN neuron and the firing rate of its CF response. Primarylike neurons exhibited various degrees of phase-locked discharges to tones at off-CF frequencies. The average upper cutoff frequency, i.e., the frequency at which the SC dropped to 0.5 of maximum value, differed for the three classes of primarylike neurons. The average cutoff frequency was respectively 183, 325, and 536 Hz for primarylike neurons that displayed low (PL 1), intermediate (PL-2), and high (PL-3) steady-state firing rates to CF stimulation. The phasic neurons showed poor phase-locking capacities at all tone frequencies. 4. The frequency range of phase-locking to amplitude-modulated stimuli was also different for the different cell types, as evidenced by the units' modulation transfer functions (MTFs). The primarylike neurons exhibited mostly all-pass or low-pass sync-based MTFs. The mean upper cutoff frequencies for primarylike neurons having low-pass MTFs were 155 Hz for PL-1 neurons, 176 Hz for PL-2 neurons, and 218 Hz for PL-3 neurons. Pauser, chopper, phasic, and phasic-burst neurons gave mostly low-pass MTFs having a mean upper cutoff frequency of 219, 235, 242, and 251 Hz, respectively. 5. The phase-locking ability of DMN neurons to tones and to amplitude-modulated stimuli are compared with those of frog's primary afferent fibers and with those of avian and mammalian cochlear nucleus neurons. The significance of results in terms of sound localization and sound pattern recognition is discussed. PMID- 7884456 TI - Projections from the pelvic nerve to the periphery of the cat's thalamic ventral posterolateral nucleus and adjacent regions of the posterior complex. AB - 1. Mapping experiments were performed in the region of the ventral posterolateral nucleus of the lateral thalamus in pentobarbitone-anesthetized cats with the aim to locate foci with input from the electrically stimulated pelvic nerve. The locations of the recording sites were verified in Nissl-stained histological sections with reference to electrolytic lesions. 2. Of the 68 visceroceptive thalamic neurons identified, 63% were located in the periphery of the ventral posterolateral nucleus (VPLp) and 34% in the dorsal, lateral, and medial aspects of the posterior complex (POd, POl, and POm, respectively) directly adjacent to VPLp. The region surrounding the middle and caudal part of the ventral posterolateral nucleus (VPL) received a much denser input from the pelvic nerve than that around the rostral pole of VPL. 3. The response latencies of the thalamic neurons to pelvic nerve stimulation ranged from 10 to 65 ms (median: 16 ms; interquartile distance: 12-20 ms) indicating a transmission of information from the pelvic space via small and large diameter myelinated fibers. 4. Seventy nine percent of the visceroceptive neurons tested (n = 58), in addition, had low threshold somatic receptive fields that were located in 67% of the cases in regions of the lower back, the thigh, the tail and/or the heel and in 26% of the cases on the hindfoot. None of the 40 visceroceptive neurons tested with noxious mechanical stimulation of the skin responded to this kind of stimulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884455 TI - Reflex patterns in postganglionic neurons supplying skin and skeletal muscle of the rat hindlimb. AB - 1. Reflex patterns were analyzed in spontaneously active postganglionic vasoconstrictor neurons supplying skeletal muscle [muscle vasoconstrictor (MVC) neurons] and hairy skin [cutaneous vasoconstrictor (CVC) neurons] of the rat hindlimb. Postganglionic activity was recorded from single units and from filaments containing the axons of several spontaneously active neurons (multiunit preparations). The animals were freely breathing or artificially ventilated and maintained, in different experiments, under three different types of anesthesia (pentobarbital, chloralose, urethan). Reflexes were elicited by stimulation of arterial baroreceptors, chemoreceptors, cutaneous nociceptors, and cold receptors and visceral receptors from urinary bladder and colon. 2. Spontaneous activity of single postganglionic neurons ranged from 0.3 to 3.6 imp/s (median 1.15 imp/s and 1.0 imp/s in MVC and CVC neurons, respectively). Postganglionic axons conducted at 0.56 +/- 0.15 m/s (mean +/- SD, MVC neurons) and 0.53 +/- 0.11 m/s (CVC neurons). There was almost no difference in the rate of spontaneous activity under the three anesthetics used and whether the animals were artificially ventilated or breathing freely. 3. Stimulation of arterial baroreceptors by increasing arterial blood pressure by > 30 mmHg with intravenous injections of phenylephrine or angiotensin led to a depression of the activity in almost all vasoconstrictor neurons. In simultaneous recordings, with an identical increase of blood pressure, the magnitude of inhibition was greater in MVC neurons than in CVC neurons. Phasic stimulation of the arterial baroreceptors by the pulse pressure wave evoked a pronounced cardiac rhythmicity in the activity of the majority of MVC neurons (78%), but in only a small fraction of CVC neurons (18%). In most CVC neurons the cardiac rhythmicity was weak (33%) or absent (49%). When quantified the difference in the degree of cardiac rhythmicity between simultaneously recorded MVC and CVC neurons was highly significant (P < 0.001). 4. Noxious mechanical stimulation of skin of the ipsilateral hindpaw activated 20/35 MVC preparations (57%) and inhibited 25/47 CVC preparations (53%). Some CVC neurons (19%) were also activated, whereas the remainder of neurons were not affected. The quality of responses to noxious stimulation was correlated with the degree of cardiac rhythmicity that the sympathetic neurons displayed in their activity. A similar reciprocal response pattern in CVC and MVC neurons, albeit less pronounced, was observed to intense cold stimuli (chlor-ethyl spray) applied to the hindlimb. 5. This reciprocal pattern of the responses of MVC and CVC neurons was not observed when nociceptors from the contralateral hindlimb were stimulated and when cold stimuli were applied to the abdominal skin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884457 TI - Patterns of excitatory and inhibitory synaptic transmission in the rat neostriatum as revealed by 4-AP. AB - 1. Synaptic potentials induced by 4-aminopyridine (4-AP) were recorded intracellularly from rat neostriatal neurons in an in vitro slice preparation. EC50 for this 4-AP action was approximately 120 microM. The threshold for activation of synaptic potentials was 5 microM. 2. 4-AP-induced synaptic potentials appeared stochastically. Most were blocked by 1 microM tetrodotoxin or 400 microM Cd2+. Therefore they reflect a release of neurotransmitters dependent on both Ca2+ entry to the terminals and action potential firing. 3. Bicuculline (BIC) (< or = 10 microM), a gamma-aminobuturic acid-A (GABAA) antagonist, blocked about half of the 4-AP-induced synaptic potentials. This suggests that intrinsic inhibitory connections within the neostriatum are activated by 4-AP administration. 4. 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; < or = 10 microM) plus D-2-amino-5-phosphonovaleric acid (D-APV; < or = 100 microM) blocked most of the BIC-resistant 4-AP-induced synaptic potentials. This suggests that 4-AP induced release of glutamate (GLU) from extrinsic glutamatergic afferents. As most glutamatergic afferents are extrinsic, these afferents then would be able to fire spikes and release transmitter for several hours after they are cut from their somata. 5. If CNQX plus D-APV were administered before BIC, neostriatal neurons responded in different ways. In one half of the neurons, all induced synaptic potentials were blocked. This suggests that most GABAergic intrinsic connections between neostriatal neurons are activated indirectly by 4-AP. 4-AP would first activate extrinsic glutamatergic afferents and these in turn would activate GABAergic intrinsic neurons and connections. 6. In the remaining half of the recorded neurons, administration of CNQX plus D-APV blocked most, but not all of the 4-AP-induced synaptic potentials. The synaptic potentials that remained had a characteristic pattern: they were high amplitude, rhythmic, bursts of synaptic potentials. They were blocked by BIC (5 microM) but not by mecamylamine (> 10 microM). This suggests that these bursts of synaptic potentials were GABAergic and generated by intrinsic neurons. Therefore these neurons would not innervate all neostriatal neurons equally but just a subset of them. 7. Records from an identified aspiny neostriatal interneuron, obtained from the same preparation, are shown. This interneuron fired in bursts and its morphologically and physiologically similar to the recently described, fast spiking, parvalbumin immunoreactive, GABAergic, aspiny interneuron is functional in the slice preparation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884458 TI - Responses of rapidly adapting neurons in cat primary somatosensory cortex to constant-velocity mechanical stimulation. AB - 1. The responses of rapidly adapting (RA) neurons to constant-velocity ramp stimulation were studied in the forepaw representation of primary somatosensory cortex (SI) of anesthetized cats. Single probe stimuli were used to indent the skin or to move hair parallel to the skin surface. The velocity of the moving stimulus probe was varied to determine the rate sensitivity of the neurons. 2. The cortical RA neurons were classified into four categories identified as G1/F1, Gint/Fint, G2/F2, and complex classes. The primary bases for classification in the present experiments were the pattern of response during ramp stimulation, velocity threshold, and directional sensitivity. 3. Of the RA neurons recorded in SI, 84% (49/58) could be assigned to one of the three response classes with little ambiguity. The remaining neurons showed more complex responses. The form of the complex responses suggested that they arose from a combination of inputs of different response classes. Some of these appeared to arise from a combination of different RA input classes, whereas others had components that resembled responses previously described for C mechanoreceptors. 4. Increased ramp velocity resulted in increased average firing frequency in 87% of the RA neurons. This relationship, which could be fitted with a power function, varied with response class. G1/F1 neurons were more sensitive to stimulus rate than G2/F2 neurons. Significant differences between response classes also were seen in the relationship between ramp velocity and their number of evoked action potentials and in their spontaneous firing rates. 5. The results demonstrate that a discrete SI neuron population is sensitive to the rate of stimulus movement. This observation is consistent with psychophysical studies reporting effects of stimulus indentation rates on perception of single probe stimuli. The appearance of complex responses in a small proportion of SI neurons provides evidence of convergence in somatosensory pathways to SI. PMID- 7884459 TI - Proprioceptive activity in primate primary somatosensory cortex during active arm reaching movements. AB - 1. We studied the activity of 254 cells in the primary somatosensory cortex (SI) responding to inputs from peripheral proprioceptors in a variety of tasks requiring active reaching movements of the contralateral arm. 2. The majority of cells with receptive fields on the proximal arm (shoulder and elbow) were broadly and unimodally tuned for movement direction, often with approximately sinusoidal tuning curves similar to those seen in motor and parietal cortex. 3. The predominant temporal response profiles were directionally tuned phasic bursts during movement and tonic activity that varied with different arm postures. 4. Most cells showed both phasic and tonic response components to differing degrees, and the population formed a continuum from purely phasic to purely tonic cells with no evidence of separate distinct phasic and tonic populations. This indicates that the initial cortical neuronal correlates of the introspectively distinguishable sensations of movement and position are represented in an overlapping or distributed manner in SI. 5. The directional tuning of the phasic and tonic response components of most cells was generally similar, although rarely identical. 6. We tested 62 cells during similar active and passive arm movements. Many cells showed large differences in their responses in the two conditions, presumably due to changes in peripheral receptor discharge during active muscle contractions. 7. We tested 86 cells in a convergent movement task in which monkeys made reaching movements to a single central target from eight peripheral starting positions. A majority of the cells (46 of 86, 53.5%) showed a movement direction-related hysteresis in which their tonic activity after movement to the central target varied with the direction by which the arm moved to the target. The directionality of this hysteresis was coupled with the movement-related directional tuning of the cells. 8. We recorded the discharge of 93 cells as the monkeys performed the task while compensating for loads in different directions. The large majority of cells showed a statistically significant modulation of activity as a function of load direction, which was qualitatively similar to that seen in motor cortex under similar task conditions. Quantitatively, however, the sensitivity of SI proprioceptive cells to loads was less than that seen in motor cortex but greater than in parietal cortex. 9. We interpret these results in terms of their implications for the central representation of the spatiotemporal form ("kinematics") of arm movements and postures. Most importantly, the results emphasize the important influence of muscle contractile activity on the central proprioceptive representation of active movements. PMID- 7884460 TI - Electrotonic architecture of cat gamma motoneurons. AB - 1. Experimental measures of input resistance, RN, and responses to brief hyperpolarizing current pulses were obtained in identified gamma-motoneurons in pentobarbital-anesthetized cats using conventional sharp micropipettes. The same cells were subsequently injected with horseradish peroxidase and completely reconstructed. In two cells, the electrophysiological and morphological data were of sufficient quality to permit estimation of specific membrane resistance, Rm, using biologically plausible ranges of specific cytoplasmic resistance, Ri, and membrane capacitance, Cm. 2. A combination of steady-state and dynamic computer models were employed to reconcile cell morphology with RN and the trajectories of the voltage decay following brief current pulses delivered to the soma. Simulated transient responses matched the tails of the observed transient when generated with the same current injections used experimentally. With Cm < or = 1.0 microF cm-2, the most satisfactory fits were obtained when the values of Rm assigned to the soma, Rms, were much smaller than the spatially uniform value assigned to the dendrites, Rmd and Ri = 60-70 omega cm. With Cm = 1.0 microF cm-2, Rms ranged from 260 to 427 omega cm2, whereas Rmd was approximately 33 K omega cm2. With Cm = 0.8 microF cm-2, Rms ranged from 235 to 357 omega cm2 and Rmd was between 62 and 68 K omega cm2. When Rm was constrained to be spatially uniform (i.e., Rm = Rms), implausibly high values of Cm (2.5-5.0 microF cm-2; Ri = 70 omega cm) were required to match the observed tail time constant, tau o,peel, but the simulated transients did not otherwise match those obtained experimentally. 3. With best fit values of Rms and Rmd, both gamma-motoneurons were electronically relatively compact (80% of total membrane area within 0.85 length constants from the soma). However, the calculated average steady-state inward attenuation factor (AFin) for voltages generated at any point within the dendrites increased rapidly with distance from the soma, reaching levels of < or = 90 and < or = 45 for the proximal 80% of membrane area for the respective motoneurons in the presence of a somatic shunt (Rms << Rmd). If we assume that the somatic shunt is an artifact of sharp micropipette penetration (i.e., that Rms = Rmd for uninjured cells), then AFin decreased to < or = 20 and < or = 15, respectively, for the proximal 80% of cell membrane.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884461 TI - Differences between presynaptic and postsynaptic GABAB mechanisms in rat hippocampal pyramidal cells. AB - 1. Whole cell voltage-clamp techniques were used in the CA1 region of rat hippocampal slices to study presynaptic and postsynaptic gamma-aminobutyric acid B (GABAB) response mechanisms. The effects of the protein kinase C activator phorbol 12,13-diacetate (PDA), barium (Ba2+), and pertussis toxin were compared on the presynaptic and postsynaptic GABAB actions of bath-applied baclofen and paired-pulse depression (PPD) of the monosynaptic GABAA inhibitory postsynaptic current (IPSC). The magnitude of PPD was dependent on the amplitude of the first response. PPD was predominantly a GABAB-mediated effect, as it was very much reduced by the GABAB antagonist CGP 35348. 2. PDA enhanced monosynaptic GABAA IPSCs through an apparently presynaptic mechanism. Iontophoretic GABAA responses were unaffected, and there was no change in EIPSC. PDA increased the frequency of spontaneous, tetrodotoxin-insensitive IPSCs without significantly affecting their amplitudes. The inactive phorbol ester, 4 alpha-PDA did not alter IPSCs. After PDA application, stimulus intensity was adjusted to produce responses of comparable amplitude to control responses. PDA had a marked and reversible depressant effect on the postsynaptic GABAB response and caused a lesser, but still significant, reduction in the baclofen-induced reduction of monosynaptic IPSCs. PDA had no effect on PPD. 3. Ba2+ dramatically reduced postsynaptic GABAB responses; it had no effect on PPD. Ba2+ tended to decrease the presynaptic baclofen reduction of IPSCs, although this was not statistically significant. 4. Pertussis toxin, injected 2-3 days earlier into the intact hippocampus, blocked all three GABAB responses equally (approximately 70% decrease). 5. We conclude that presynaptic and postsynaptic GABAB mechanisms are mediated by G proteins that couple to different mechanisms. Discrepancies with previous work are evidently due to the use of different tissue preparations and different target responses. Even though protein kinase C activation caused a partial reduction in the presynaptic effect of baclofen, its lack of effect on PPD makes a significant role for protein kinase C in modulation of PPD unlikely. PMID- 7884462 TI - Age-related epileptogenic effects of corticotropin-releasing hormone in the isolated CA1 region of rat hippocampal slices. AB - 1. The effects of corticotropin-releasing hormone (CRH) on synaptically evoked population and intracellular responses in the isolated rat CA1 region of hippocampal slices were studied to evaluate possible differences between adult and juvenile rats. 2. The amplitude of orthodromically evoked (stratum radiatum stimulation) population spikes was reversibly enhanced by 0.2-0.6 microM CRH to a greater extent in slices from juvenile rats than from adult rats. In no case, however, did CRH cause seizure-like activity to develop under normal recording conditions. 3. In the presence of 10-30 microM bicuculline, interictal-like bursts of population spikes and corresponding intracellularly recorded action potentials could be evoked starting at postnatal day 8. The number of spikes and the duration of the evoked bursts in the CA1 region were reversibly increased by CRH (0.2-0.6 microM) to a greater extent in slices from juvenile than from adult rats. 4. The amplitude of the afterhyperpolarization following intracellularly evoked bursts of action potentials in CA1 pyramidal cells was reduced by 0.2 microM CRH to a similar degree in both young and adult rats. No consistent changes in input resistance or membrane potential were observed. 5. No correlation was found between the magnitude of the CRH-induced increase in responsiveness and the initial excitability in controls, suggesting that the CRH induced changes were independent of any age-dependent differences in general slice excitability. 6. Our results indicate that, in the CA1 region, CRH augments bicuculline-induced bursts to a greater extent in slices from young versus adult rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884463 TI - Neuronal responses in cat primary auditory cortex to electrical cochlear stimulation. I. Intensity dependence of firing rate and response latency. AB - 1. Responses of neurons in primary auditory cortex (AI) of the barbiturate anesthetized adult cat were studied using cochlear stimulation with electrical and acoustic stimuli. Acoustic stimulation of the ear ipsilateral to the studied cortical hemisphere with brief biphasic clicks was compared with electrical stimulation of the contralateral cochlea with brief biphasic electrical pulses delivered via a feline cochlear prosthesis. The contralateral ear was deafened immediately before implantation of the cochlear prosthesis. The feline cochlear prosthesis consisted of four bipolar electrode pairs and was placed in the scala tympani. Two bipolar electrode conditions were used for stimulation: one near radial pair with electrode spacing of approximately 0.5 mm, and one longitudinal pair with electrode spacing of approximately 6 mm. 2. The firing rates obtained from single- and multiple-neuron recordings were measured as a function of stimulus intensity for single electrical and acoustic pulses. Resulting rate/level functions were characterized by a fast growing low-level segment and a more slowly growing, saturating, or decreasing high-level segment. The slopes of these two segments as well as the stimulus level and firing rate at the juncture of these two segments (the transition point) provide a complete characterization of the response magnitude behavior as a function of stimulus intensity. 3. The main characteristics of rate/level functions obtained with electrical and acoustic cochlear stimulation were quite similar. However, for any given neuron, differences in the primary growth behavior, such as monotonic or nonmonotonic growth, could be observed between the different stimulation modes. 4. Response latencies from single- and multiple-neuron recordings were obtained as a function of stimulus intensity for electrical and acoustic pulses. Resulting latency/level functions were characterized by a rapidly decreasing low-level segment and a more slowly decreasing high-level segment. The slopes of these two segments as well as the stimulus level and response latency at the juncture of these two segments (the transition point) provide a complete characterization of the response latency behavior as a function of stimulus intensity. Transition point levels for the rate/level function and the latency/level were nearly identical. 5. The characteristic latency behavior for each neuronal response was found to be very similar for acoustic and electrical stimulation. Correlation analysis revealed a close relationship between latency parameters of the two electrical stimulation conditions, a weaker relationship between the longitudinal electrical and the acoustic conditions, and the weakest relationship between the radial electrical and acoustic conditions. 6. Correlation analysis for rate and latency parameters revealed several relationships between these response aspects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884464 TI - GABAB and adenosine receptors mediate enhancement of the K+ current, IAHP, by reducing adenylyl cyclase activity in rat CA3 hippocampal neurons. AB - 1. Gamma-aminobuturic acid-B (GABAB) and adenosine A1 receptors, which are expressed in hippocampal pyramidal cells, are linked to pertussis toxin-sensitive G-proteins known to be coupled negatively to the enzyme adenylyl cyclase. This study investigates the electrophysiological consequences of adenylyl cyclase inhibition in response to stimulation of these receptors. 2. Single-electrode voltage-clamp recordings were obtained from CA3 pyramidal cells in rat hippocampal slice cultures in presence of tetrodotoxin. The calcium-dependent potassium current (IAHP), which is very sensitive to intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP), was used as an electrophysiological indicator of adenylyl cyclase activity. 3. Application of baclofen (10 microM), a selective agonist at GABAB receptors, or adenosine (50 microM) each resulted in a transient decrease followed by a significant enhancement in the amplitude of evoked IAHP. The initial reduction in amplitude of IAHP probably reflects inadequacies in voltage clamp of electronically distant dendritic sites, due to the shunting caused by concomitant activation of potassium conductance by baclofen/adenosine. Comparable increases in membrane conductance in response to the GABAA agonist, muscimol, caused a similar reduction in IAHP. The enhancement of IAHP is consistent with an inhibition of constitutively active adenylyl cyclase. 4. The receptor mediating the responses to adenosine was identified as belonging to the A1 subtype on the basis of its sensitivity to the selective antagonist 8-cyclopentyl-1,3-dipropylxanthine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884465 TI - Behavior of identified Edinger-Westphal neurons during ocular accommodation. AB - 1. The present study used single-unit recording and antidromic activation techniques in alert rhesus monkeys to examine the static and dynamic behavior of 21 parasympathetic, preganglionic neurons of the Edinger-Westphal nucleus (EW) during ocular accommodation. 2. All identified EW neurons were active when viewing at optical infinity with an average firing rate of 11.6 spikes/s. During near viewing, there was a linear relationship between firing rate and accommodation with an overall gain for the population of preganglionic EW neurons of 3.3 (spikes/s)/diopter. 3. The activity of eight identified EW neurons was studied during viewing of targets with conflicting vergence and accommodative demands to dissociate their vergence and accommodation responses. With normal viewing these responses are so closely matched that it cannot be determined if the activity of a cell is related to vergence or to accommodation, but with dissociated viewing these relationships can be determined. Under this viewing condition, six preganglionic EW neurons showed the same relationship to accommodation as they did during normal viewing. However, the activity of two cells could not be explained solely by accommodation, and they showed some activity related to vergence. 4. Microstimulation at the sites of identified EW neurons produced accommodation in the ipsilateral eye. Repeated measures of the effect of microstimulation yielded a value of 75 ms for the latency of the response. This latency was essentially the same in both animals tested. 5. The activity of identified EW neurons is related to the velocity of accommodation as well as to static accommodation. The relationship between accommodation velocity and firing rate was studied for 15 identified EW neurons during sine-wave tracking of targets moving in depth. All of these cells showed a clear relationship between firing rate and accommodation velocity. Overall, this group of identified EW neurons showed a velocity sensitivity of 1.2 (spikes/s)/(diopter/s) and an estimated neural time constant of 380 ms. 6. Eleven neurons encountered near to preganglionic EW neurons could not be antidromically activated by stimulation of the oculomotor nerve. These neurons had statistically higher gains with respect to the near response; indeed, there was no overlap between the gains of these neurons and the gains of preganglionic EW neurons. Upon dissociation of vergence from accommodation, they were found to be related to either vergence or to vergence and accommodation but not solely to accommodation. PMID- 7884466 TI - Functional organization of sound direction and sound pressure level in primary auditory cortex of the cat. AB - 1. The functional organization of neuronal tuning to the azimuthal location and sound pressure level (SPL) of noise bursts was studied in high-frequency primary auditory cortex (AI) of barbiturate-anesthetized cats. Three data collection strategies were used to map neural responses: 1) electrode penetrations oriented normal to the cortical surface provided information on the radial organization of neurons' responses; 2) neurons' responses were examined at a few points in the middle cortical layers in multiple normal penetrations across AI to produce fine grain maps of azimuth and level selectivity; and 3) electrode penetrations oriented tangential to the cortical surface provided information on neurons' responses along the isofrequency dimension. 2. An azimuth-level data set was obtained for each single- or multiple- (multi-) unit recording; this consisted of responses to noise bursts at five SPLs (0-80 dB in 20-dB steps) from seven azimuthal locations in the frontal hemifield (-90 to +90 degrees in 30 degrees steps; 0 degree elevation). An azimuth function was derived from these data by averaging response magnitude over all SPLs at each azimuth tested. A preferred azimuth range (PAR; range of azimuths over which the response was > or = 75% of maximum) was calculated from the azimuth function and provided a level independent measure of azimuth selectivity. Each PAR was assigned to one of four azimuth preference categories (contralateral-, midline-, ipsilateral-preferring, or broad/multipeaked) according to its location and extent. A level function obtained from the data set (responsiveness averaged over all azimuths) was classified as monotonic if it showed a decrease of < or = 25% (relative to maximum) at the highest SPL tested (usually 80 dB), and nonmonotonic if it showed a decrease of > 25%. The percentage reduction in responsiveness, relative to maximum, at the highest level tested (termed nonmonotonic strength) and the preferred level range (PLR; range of SPLs over which responsiveness was > or = 75% of maximum) of each response was also determined. 3. Normal penetrations typically showed a predominance of one azimuth preference category and/or level function type. The majority of penetrations (26/36: 72.2%) showed statistically significant azimuth preference homogeneity, and approximately one-half (17/36: 47.2%) showed significant level function type homogeneity. Over one-third (13/36) showed significant homogeneity for both azimuth preference and level function type. 4. Mapping experiments (n = 4) sampled the azimuth and level response functions at two or more depths in closely spaced normal penetrations that covered several square millimeters of AI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884467 TI - Synaptic transmission between ventrolateral funiculus axons and lumbar motoneurons in the isolated spinal cord of the neonatal rat. AB - 1. We studied the projections of ventrolateral funiculus (VLF) axons to lumbar motoneurons in the in vitro spinal cord preparation of 1- to 6-day-old rats using extracellular and sharp-electrode intracellular recordings. 2. Ipsilateral and contralateral VLF projections to lumbar motoneurons (L4-L5) could be activated in the neonatal rat by stimulation of the surgically peeled VLF at the rostral (L1 L2) and caudal lumbar (L6) cord. Motoneurons were activated ipsilaterally through short- and long-latency projections in all cases and contralaterally through long latency projections in most cases. 3. Suppression of the excitatory components of VLF postsynaptic potentials (PSPs) by application of the specific antagonists of N-methyl D-aspartate (NMDA) and non-NMDA receptors, 2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquin-oxaline-2,3-dione (CNQX), revealed depolarizing PSPs that could be reversed at -55 to -60 mV by injection of depolarizing current steps to the motoneurons. These depolarizing PSPs were blocked by addition of strychnine and bicuculline and are therefore suggested to be glycine and gamma-aminobutyric acid-A (GABAA) receptor-mediated inhibitory PSPs. The identity of a small (< or = 0.2 mV) residual depolarizing component that persisted in the presence of APV, CNQX, strychnine, and bicuculline remains to be determined. 4. Short-latency excitatory PSPs (EPSPs) could be resolved from the ipsilaterally elicited VLF PSPs after the reduction of the polysynaptic activity in the preparation by administration of mephenesin, which was followed by suppression of the glycine and GABAA receptor-mediated components of the PSPs by bath application of strychnine and bicuculline. The latencies of these EPSPs were similar to those of the monosynaptic dorsal root afferent EPSPs recorded from the same motoneurons. These short-latency VLF EPSPs were shortened by the NMDA antagonist APV and revealed an NMDA receptor-mediated component after administration of the non-NMDA receptor antagonist CNQX. Addition of the GABAB receptor agonist L-(-) baclofen or the glutamate analogue L-2-amino-4 phosphonobutyric acid (L-AP4) attenuated the pharmacologically resolved short latency EPSPs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884468 TI - Mechanosensitive properties of pelvic nerve afferent fibers innervating the urinary bladder of the rat. AB - 1. Single-unit activity was recorded from S1 dorsal root afferent fibers in pentobarbital-anesthetized rats. In 25 experiments, 245 afferent fibers were identified by electrical stimulation of the pelvic nerve. Fifty-two percent were C fibers (conduction velocity: 1.70 +/- 0.04 m/s; mean +/- SE) and 48% were A delta-fibers (conduction velocity: 11.07 +/- 0.95 m/s). 2. Of 245 pelvic nerve afferent fibers, 92 (38%) responded to noxious urinary bladder distension (UBD; 80 mmHg); 57 of these fibers were C fibers and 35 were A delta-fibers. Forty-four fibers responded to colorectal distension (CRD; 80 mmHg); 32 were C fibers and 12 were A delta-fibers. A total of 39 fibers were identified in the anal mucosa; 3 were C fibers and 36 were A delta-fibers. Seventy fibers (28%) in these experiments were unresponsive to either UBD or CRD or to probing of the anal mucosa; 32 were unmyelinated C fibers and 38 were A delta-fibers. 3. Reproducibility of responses to repeated UBD (80 mmHg, 20 s; 8 trials at 4-min intervals) was tested in 10 fibers. In nine fibers, responses to repeated distension did not change; one fiber exhibited a progressive decrease in response magnitude after the third trial. 4. Of the 92 afferent fibers that responded to UBD, 45 were further characterized for responses to graded intensities of UBD. Forty fibers had some resting activity (1.7 +/- 0.3 impulses/s) and five fibers exhibited no ongoing activity. The response to UBD adapted slowly during the 20-s period of phasic UBD or during slow isotonic filling of the bladder. 5. The stimulus-response function (SRF) of fibers (n = 45) to graded UBD was monotonic < or = 80 mmHg. Thresholds for responses were determined after extrapolation of the least-squares linear regression line to the ordinate, and varied between 0 and 45 mmHg. The frequency distribution profile of thresholds revealed two populations of pelvic nerve afferent fibers in the urinary bladder: a larger group (n = 36) of low-threshold (LT) fibers (5.7 +/- 1.0 mmHg) and a smaller group (n = 9) of high-threshold (HT) fibers (34 +/- 2.5 mmHg). 6. Responses of four LT fibers to graded UBD were tested before and 30 min after instillation of 0.5 ml of 0.5% acetic acid (pH 3) into the bladder. The mean threshold for response of these fibers before instillation of acetic acid (9.4 +/- 3.1 mmHg) more than doubled (to 22.3 +/- 6.7 mmHg) after instillation of acetic acid.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884469 TI - Effects of posture on the coordination of respiration and swallowing. AB - 1. Although a pause in respiration during swallowing is a feature common to all mammals, inhibition usually occurs during expiration in adult humans and during inspiration in most other species. We tested the hypothesis that this difference is due, at least in part, to the position of the body while feeding. 2. The coordination of respiration and swallowing was studied in adult human subjects in two body positions; upright, which is typically human, and on hands and knees, which is similar to the feeding posture of most other animal species. 3. Our major finding was that the respiratory phase in which swallowing occurred was significantly related to posture. Swallows tended to occur late in the expiratory phase while feeding upright, but during early expiration while on all fours. 4. We speculate that the phase of respiration in which swallowing occurs changes with posture to compensate for the alterations in the mechanical properties of the upper body. PMID- 7884471 TI - Gaze strategies during linear motion in head-free humans. AB - 1. Eye-head coordination strategies during horizontal displacements along the y (interaural) axis were investigated in human subjects seated on a sled (linear accelerator device) and tested in head-free conditions. They were instructed to stabilize their gaze, while in motion, on an earth-fixed memorized target and then, after cart immobilization, to look again at the real target. The last part of the test required a corrective saccade, which enabled us to evaluate the error of the subject's displacement estimation. Eye and head compensatory reflexes were tested within the 0.001-0.2 g acceleration range with a sinusoidal motion amplitude of 0.8 m peak to peak. 2. Fixation stabilization on a memorized target was achieved by different eye-head coordination strategies. According to the relative contribution of eye and head motion, a continuum among individual strategies was observed, covering a range of head contributions varying from 0 to almost 100%. All these strategies were well adapted because they contributed to the counteraction of the displacement and led to an optimal gaze accuracy. 3. The use of various gaze strategies during linear motion to achieve the same movement differed according to the subject, but also depended upon motion kinematics. As a rule, head contribution increased as the magnitude of linear acceleration was enhanced. 4. Different eye-head coordination strategies implicated either a linear vestibulo-ocular reflex (LVOR) or ocular responses composed of a combination of antagonistic angular and linear vestibulo-ocular reflexes (AVOR LVOR). The slow phase direction of these two oculomotor responses for fixation stabilization on the target were compensatory and anticompensatory, respectively. 5. One of the major points of this study was the contribution of the saccadic system to gaze strategies, even in our experimental conditions where the head was free to move. We concluded that vestibular-saccadic cooperation appears to be a common feature in the elaboration of adequate fixation stabilization in daily life situations. 6. The functional coupling of these various subsystems involved in fixation stabilization depended on the range of motion: while the acceleration increased, the saccadic eye movements were replaced by vestibulo-ocular responses whose slow phase direction was opposite that of head motion and, therefore, directed away from the target. 7. Fast components of the nystagmic pattern of eye movements were able to improve gaze position accuracy, bringing the eyes toward the memorized target.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884470 TI - Effects of 5-HT on thalamocortical synaptic transmission in the developing rat. AB - 1. Recent immunocytochemical and receptor binding data have demonstrated a transient somatotopic patterning of serotonin (5-HT)-immunoreactive fibers in the primary somatosensory cortex of developing rats and a transient expression of 5 HT1B receptors on thalamocortical axons from the ventral posteromedial thalamic nucleus (VPM). 2. These results suggest that 5-HT should strongly modulate thalamocortical synaptic transmission for a limited time during postnatal development. This hypothesis was tested in intracellular recording experiments carried out in thalamocortical slice preparations that included VPM, the thalamic radiations, and the primary somatosensory cortex. Effects of 5-HT and analogues were monitored on membrane potentials and input resistances of cortical neurons and on the amplitude of the synaptic potentials evoked in them by stimulation of VPM. 3. Results obtained from cortical neurons in slices taken from rats during the first 2 wk of life indicated that 5-HT strongly inhibited the VPM-evoked excitatory postsynaptic potential (EPSP) recorded from cortical neurons in a dose dependent manner. In contrast, 5-HT had no significant effects on membrane potential, input resistance, or depolarizations induced by direct application of glutamic acid to cortical cells. 4. The effects of 5-HT were mimicked by the 5 HT1B receptor agonists 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP) and 7 trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]-quinoxaline maleate and antagonized by the 5-HT1B receptor antagonist (-)-pindolol. The 5-HT1A agonist [(+/-)8-hydroxydipropylaminotetralin HBr] (8-OH-DPAT) had less effect on the VPM elicited EPSP, and the effects of 5-HT upon this response were generally not antagonized by either 1-(2-methoxyphenyl)-4-[4-(2- phthalimmido)butyl]piperazine HBr (a 5-HT1A antagonist) or ketanserine (a 5-HT2 antagonist) or spiperone (a 5 HT1A and 2 antagonist). 5. The ability of 5-HT to inhibit the VPM-evoked EPSP in cortical neurons was significantly reduced in slices from animals > 2 wk of age. The effectiveness of TFMPP in such animals was even more attenuated than that of 5-HT, and the effectiveness of 8-OH-DPAT was unchanged with age. These results are consistent with the disappearance of 5-HT1B receptors from thalamocortical axons after the second postnatal week and the maintenance of 5-HT1A receptors on some neurons. 6. All of the results obtained in this study are consistent with the conclusion that 5-HT has a profound, but developmentally transient, presynaptic inhibitory effect upon thalamocortical transmission in the rat's somatosensory cortex. PMID- 7884472 TI - Rotational kinematics of the human vestibuloocular reflex. I. Gain matrices. AB - 1. This series of three papers aims to describe the three-dimensional, kinematic input-output relations of the rotational vestibuloocular reflex (VOR) in humans, and to identify the functional advantages of these relations. In this first paper the response to sinusoidal rotation in darkness at 0.3 Hz, maximum speed 37.5%/s, was quantified by the use of the three-dimensional analogue of VOR 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. 2. The three matrix elements indicating collinear gains (i.e., dependence of torsional eye velocity on torsional head velocity, vertical on vertical, and horizontal on horizontal) were smaller than the -1's required for optimal retinal image stabilization. Of these three the torsional gain was weakest: -0.37 for rotation about an earth-vertical axis, versus -0.73 and -0.64 for vertical and horizontal gains. Matrix elements indicating cross talk were mostly negligible. There was a tendency to leftward eye rotation in response to clockwise head motion, but this was not statistically significant. 3. VOR responses were compared for rotation about earth-vertical and earth-horizontal axes. The varying otolith input due to the rotation of the gravity vector relative to the head during earth-horizontal axis rotation made no difference to the collinear gains. 4. There were no consistent phase leads or lags except for a torsional phase lead of up to 10 degrees, usually more marked for clock-wise head rotation versus counterclockwise, and for oblique axis rotations versus purely torsional. 5. Torsional gain was magnified, averaging -0.52, when the torsional component of head rotation was only a small part of a predominantly vertical or horizontal rotation, i.e., when the axis of head rotation was near the frontal plane. Because most natural head rotations occur about such axes, the torsional VOR is probably somewhat stronger than the response to pure torsion would suggest. 6. The speed of eye rotation in response to a given stimulus varied widely among subjects, but the direction of rotation was much more uniform. For head rotations about oblique axes out of the frontal plane, there was a systematic misalignment of eye and head axes, with eye axes tilted toward the frontal plane. These findings can be explained on the basis of a strategy where the VOR balances the muscular effort of rotating the eyes against the cost of retinal slip. PMID- 7884473 TI - Rotational kinematics of the human vestibuloocular reflex. II. Velocity steps. AB - 1. Gain matrices were used to quantify the three-dimensional vestibuloocular reflex (VOR) in five human subjects who were accelerated over 1 s and then spun at a constant 150 degrees/s for 29 s in darkness. Rotations were torsional, vertical and horizontal, about earth-vertical and earth-horizontal axes. 2. Elements on the main diagonal of the gain matrices were much smaller than the optimal value of -1, and torsional gain was weaker than vertical or horizontal. Off-diagonal elements, indicating cross talk, were minimal except for a small but consistent horizontal response to torsional head rotation. 3. Downward slow phases were more than twice as fast as upward at the start of rotation about both earth-vertical and earth-horizontal axes, but the asymmetry vanished later in the rotation. 4. During earth-vertical-axis rotation, all matrix elements decayed to zero. The main-diagonal torsional and vertical gains waned with time constants close to that of the cupula (6.7 and 7.3 s). Velocity storage prolonged the horizontal response to horizontal head rotation (time constant 14.2 s) but not the horizontal response to torsion (7.7 s). A simple explanation is that velocity storage acts on a central estimate of head motion that accurately distinguishes horizontal from torsional and that the inappropriate horizontal eye velocity response to torsion occurs because of cross talk downstream from velocity storage. 5. During earth-horizontal-axis rotation, the torsional, vertical, and horizontal main-diagonal elements declined, with time constants of 7.6, 8.2, and 7.9 s, to maintained nonzero values, all equal to about -0.1. Off-diagonal elements, including the horizontal response to torsion, decayed to zero, so that the otolith-driven reflex, late in the rotation, was equally strong in all dimensions and almost free of detectable cross talk. 6. The difference between gain curves over the course of earth-vertical- and earth-horizontal-axis rotations was not constant but increased with time, suggesting that the VOR response to earth-horizontal-axis rotation is not a simple sum of canal and otolith reflexes. PMID- 7884474 TI - Rotational kinematics of the human vestibuloocular reflex. III. Listing's law. AB - 1. Do slow phase eye velocities generated by the vestibuloocular reflex (VOR) depend on eye position? If the purpose of the VOR is simply to stabilize the retinal image, there can be no such dependence, because eye velocity must always be equal and opposite to head velocity. But if the VOR tolerates some retinal slip to achieve other goals, such as reducing eye velocity or following Listing's law, then one should see specific patterns of dependence. We examined VOR responses of human subjects to yaw, pitch, and roll rotation looking in various directions to quantify how the input-output properties of the VOR vary with eye position. 2. Eye rotation axes during yaw and pitch tilted in the same direction as the gaze line but only one-quarter as far on average. Thus, during yaw head rotation, the axis of eye rotation was roughly aligned with the head axis when the subject looked straight ahead, but tilted up when the gaze direction was up, and down when gaze was down. The amount of tilt varied between subjects, but on average a 30 degrees change in eye position caused a 7.5 degrees tilt in the eye rotation axis. During pitch, the eye axis tilted right when gaze was right and left when gaze was left, also moving 7.5 degrees on average for a 30 degrees change in the gaze direction. 3. During roll stimulation, the axis of eye rotation tilted in the opposite direction to the gaze line, and about one-half as far. On average, when the gaze line moved 30 degrees down, the eye rotation axis tilted 12.0 degrees up; when the gaze moved 30 degrees left, the eye axis tilted 15.3 degrees right. 4. It is often argued that the torsional VOR is weak because head rotation about the line of sight causes little image displacement on the fovea. But the line of sight is collinear with the torsional axis only when the subject looks straight ahead. Does the "weak axis" of the VOR stay collinear with the gaze line when the subject looks eccentrically? We calculated the axis of head rotation for which the VOR response is weakest and found that it does vary with eye position, but does not stay parallel with the gaze direction. When subjects looked straight ahead, the weak axis was roughly collinear with the gaze line; when gaze shifted eccentrically, the weak axis shifted in the same direction but only about one-half as far.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884476 TI - Reorganization of cortical blood flow and transcranial magnetic stimulation maps in human subjects after upper limb amputation. AB - 1. Two complimentary techniques were used to study cortical function in six human upper limb amputees: positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) were made in subjects during limb movements to study activation of the primary motor (M1), primary somatosensory (S1), and association cortices; and electromyographic responses to transcranial magnetic stimulation (TMS) were measured in proximal upper limb muscles to assess the excitability of corticospinal neurons in subjects at rest. 2. To explore possible cortical mechanisms governing the phantom limb phenomenon, PET and TMS findings were compared between subjects with acquired, traumatic upper limb amputations (n = 3), in whom phantom limb symptoms were prominent, and congenital upper limb amputees (n = 3) without phantom limbs. 3. Paced shoulder movements were associated with significant blood flow increases in the contralateral M1/S1 cortex of both groups of amputees. In traumatic amputees, these increases were present over a wider area and were of significantly greater magnitude in the partially deafferented cortex contralateral to the amputation. In congenital amputees blood flow increases were also present over a wider area in the partially deafferented M1/S1 cortex, but their magnitude was not significantly different from that in the normally afferented M1/S1 cortex. 4. Abnormal blood flow increases also were present in the partially deafferented M1/S1 cortex of traumatic amputees during movement of the ipsilateral, intact arm. Abnormal ipsilateral M1/S1 responses were not present during movement of the intact arm in the congenital group. 5. TMS studies showed that the abnormal blood flow increases in the partially deafferented M1 cortex of traumatic amputees were associated with increased corticospinal excitability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884475 TI - Differential role of two Ca(2+)-permeable non-NMDA glutamate channels in rat retinal ganglion cells: kainate-induced cytoplasmic and nuclear Ca2+ signals. AB - 1. The permeability of non-N-methyl-D-aspartate (non-NMDA) glutamate channels to divalent cations and specifically the entry of Ca2+ and subsequent elevations in cytoplasmic and nuclear Ca2+ signals were investigated in cultured neonatal rat retinal ganglion cells using the whole cell patch-clamp technique and Ca2+ imaging with confocal microscopy. In addition, divalent-permeable non-NMDA receptor channels were studied in retinal slices using a Co2+ staining technique. 2. Using Ca2+ (2.5 mM) as the only permeable cation in the external solution, stimulation with 100 microM kainate produced nondesensitizing, nonselective cation currents with either low or high Ca2+ permeability. Both currents were reversibly blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Neurons with the low divalent-permeable currents (type 1) had reversal potentials of -41.5 +/- 4.4 mV (mean +/- SD), and neurons with the high divalent-permeable currents (type 2) had reversal potentials of -22.6 +/- 5.5 mV. The permeability ratio PCa/PCs was 3.3 for the type 1 currents and 8.5 for the type 2 currents, indicating a 2.5 fold greater permeability to Ca2+ for the type 2 non-NMDA glutamate channels. 3. Both types of non-NMDA glutamate channels showed relatively little selectivity between Ca2+ and Co2+. The type 1 neurons had a slightly higher permeability to Co2+ than to Ca2+, whereas the type 2 neurons were equally permeable to both divalent cations. The type 2 neurons had a much higher permeability for both divalent cations compared with the type 1 neurons. 4. Staining for Co2+ uptake through kainate-stimulated non-NMDA glutamate channels in retinal slices provided additional evidence for the presence of the two ganglion cell populations. Activation of the neurons by kainate in conditions isolating the non-NMDA glutamate channel caused differential uptake of Co2+. In contrast, depolarization in the presence of the non-NMDA antagonist CNQX failed to cause Co2+ influx. 5. Imaging experiments using confocal microscopy showed that kainate stimulation induced an increase in intracellular Ca2+ in both types of retinal ganglion cells, but only the type 2 neurons showed a substantial increase in cytoplasmic and nuclear Ca2+ signals. Kainate-induced Ca2+ signals in the type 2 neurons were almost nine times greater than those of the type 1 neurons. 6. When intracellular Ca2+ stores were depleted by brief treatment with thapsigargin, kainate-induced Ca2+ signals in the type 1 neurons were unchanged. However, in the type 2 neurons kainate no longer induced large Ca2+ signals in the cytoplasm and nucleus, despite normal influx of Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884477 TI - Alpha subunit of calcium/calmodulin-dependent protein kinase enhances excitatory amino acid and synaptic responses of rat spinal dorsal horn neurons. AB - 1. Here we report that in acutely isolated rat spinal dorsal horn (DH) neurons, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate and N-methyl-D-aspartate (NMDA) receptors can be regulated by endogenous and exogenous calcium/calmodulin-dependent protein kinase II (CaM-KII). Intracellularly applied, the alpha-subunit of CaM-KII enhanced AMPA/kainate and NMDA currents recorded with the use of the whole cell patch-clamp technique. 2. Microcystin, a nonselective phosphatases inhibitor, also enhances AMPA and NMDA responses. 3. Conventional intracellular recordings were made from substantia gelatinosa neurons in spinal cord slices to determine the effect of intracellular application of CaM-KII on excitatory synaptic potentials evoked by electrical stimulation of primary afferent fibers. Excitatory synaptic transmission was enhanced by CaM-KII, which is consistent with the importance of phosphorylation of the postsynaptic AMPA/kainate and NMDA receptor-ion complexes in the short- and long-term changes in synaptic transmission. PMID- 7884478 TI - Physiological correlate of fixation disengagement in the primate's frontal eye field. AB - 1. We recorded from the frontal eye field (FEF) of rhesus monkeys while they performed the gap task in which the fixation point disappears 200 ms before the appearance of the peripheral saccadic target. This gap allows the disengagement of fixation to begin before the acquisition of saccade coordinates, thereby greatly reducing saccade latency ("gap effect"). Very short-latency saccades obtained in this gap task have been called "express saccades". 2. We studied 145 FEF neurons that had presaccadic activity on conventional saccade tasks. When tested in the gap task with a 200-ms gap, nearly half of these neurons (69) increased their discharge rate in response to the disappearance of the fixation target. We call this increase a fixation-disengagement discharge (FDD). The mean latency of the start of the FDD relative to the fixation light extinction was 149 +/- 36 (SD) ms. 3. Gap-task trials with the saccade target in the cell's response field were randomly intermixed with trials having the target opposite to the cell's field. The FDD was present in both cases: on trials into the response field, the FDD was followed by the cell's presaccadic burst. On trials opposite the cell's field, the FDD activity was suppressed prior to the saccade. 4. The FDD was most likely to be found in cells that had the movement type of presaccadic activity, i.e., movement cells and visuomovement cells. FDD was observed in 57% of visuomovement cells A, B, and C, 50% with movement activity, and 18% purely visual.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884480 TI - Retinal ganglion neurons express a toxin-resistant developmentally regulated novel type of high-voltage-activated calcium channel. AB - 1. High-voltage-activated Ca2+ currents [ICa(HVA)] were studied in immunolabeled mouse retinal ganglion neurons (RGNs) to elucidate channel-specific components and their developmental changes in vitro. 2. Neurons were dissociated at postnatal day 5. RGNs were selected for electrophysiological measurements by vital labeling with an antibody against Thy-1.2. ICa(HVA) were recorded with patch electrodes in the whole cell configuration at a holding voltage (Vh) of -90 mV. 3. A total of 111 neurons was studied. On average, 13% of ICa(HVA) was reversibly blocked by 10 microM nifedipine, approximately 30% of the compound current displayed an irreversible block by 2.5 microM omega-conotoxin (omega-CTX) GVIA. The remainder current was resistant to both drugs, suggesting that the total ICa(HVA) was a mixture of at least three different components. 4. Developmental analysis revealed a significant increase of the omega-CTX GVIA/nifedipine-resistant component of ICa(HVA) (31% at day in vitro (DIV) 0-2, 70% at DIV 18-26) mainly at the expense of the omega-CTX-GVIA-sensitive current. No significant change was found in the nifedipine-sensitive component of ICa(HVA). 5. To characterize the Ca2+ current component that was resistant to both omega-CTX-GVIA and nifedipine at Vh -90 mV, three tests were performed. The P channel antagonist omega-agatoxin IVA (omega-Aga-IVA, 200 nM) completely failed to block ICa(HVA) in mouse RGNs. The novel Ca2+ channel blocker omega-CTX-MVIIC (5 microM) decreased the ICa(HVA) remaining after omega-CTX-GVIA treatment by only approximately 10%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884479 TI - Development of thyrotropin-releasing hormone and norepinephrine potentiation of inspiratory-related hypoglossal motoneuron discharge in neonatal and juvenile mice in vitro. AB - 1. The ontogeny of thyrotropin-releasing hormone (TRH) and norepinephrine (NE) potentiation of inspiratory-related hypoglossal (XII) motor nerve discharge was studied in medullary slices from P0-3, P7, and P11-14 mice that retain functional networks for respiration. 2. TRH, applied locally to the XII motor nucleus, had no effect on XII inspiratory burst amplitude in slices from P0-3 mice. By P7 there was significant potentiation of burst amplitude that increased more than three-fold by P11-14. NE applied to the XII nucleus produced significant potentiation in all age groups. Potentiation increased developmentally with the largest increase occurring between P0-3 and P7. 3. Thus catecholamine and TRH modulation of inspiratory-related XII nerve activity increases during the first two weeks of life; the potentiating effects of NE appear prior to those of TRH. 4. With rhythmically active, transverse medullary slices from mice up to 2 wk of age, it is now possible to study the development of XII motoneuron modulation as it relates to respiratory control of the upper airway. PMID- 7884481 TI - Cerebellar contribution to the spatial encoding of orienting gaze shifts in the head-free cat. AB - 1. Cerebellar saccadic dysmetria may result from a disturbance in the processes that ensure correct execution of gaze displacement. Alternatively, an impairment in the preparatory processes that lead to the specification of the movement goal may also produce this deficit. 2. We report here on a pharmacologically induced dysmetria that suggests a cerebellar contribution to the neural processes encoding the location of the goal for orienting gaze shifts. 3. Shifts of gaze (eye-in-space) were recorded in the head-free cat after the GABA agonist muscimol was unilaterally injected into the caudal part of the fastigial nucleus. 4. Gaze saccades towards the inactivated side were hypermetric. These ipsiversive movements overshot the target by a constant error, regardless of target eccentricity and initial gaze position. 5. Gaze saccades directed away from the inactivated side undershot the target. The degree of hypometria increased when the amplitude of the required movement increased. 6. These results suggest a different contribution of the caudal fastigial nucleus to the accuracy of visually triggered gaze shifts, depending on the direction of the impending saccade. The systematic error of ipsiversive movements and the inappropriate movements evoked by presenting a target at the same physical location as gaze reveal that fastigial inactivation interfered with the processes that encode the location of a visual target. PMID- 7884482 TI - Serotonin inhibits high-threshold Ca2+ channel currents in capsaicin-sensitive acutely isolated adult rat DRG neurons. AB - 1. The effect of serotonin (5HT) was studied on high-threshold Ca2+ channel currents in a subpopulation of acutely isolated rat dorsal root ganglion cell bodies that had long-duration action potentials, lacked IH current, were capsaicin-sensitive, and thus resembled C-type nociceptors. 2. In these neurons, 10 microM 5HT inhibited peak high-threshold Ca2+ channel currents by 61.5 +/- 6.9% (mean +/- SE), (n = 7). The effects of 5HT were mimicked by 1 microM (+)8 hydroxy-2-(di-n-propylamino)-tetralin HBr [(+)8-OH-DPAT] in five neurons tested, and the effects of 1 microM (+)8-OH-DPAT were antagonized by 100 nM 1-(2 methoxyphenyl)-4-[4-(2-phthalimmido)butyl]piperazine HBr (NAN-190) in six neurons tested. 3. The above data leads us to hypothesize that 5HT, released into the spinal cord by descending systems, may produce antinociception by inhibiting Ca2+ entry into afferent terminals of nociceptors via activation of 5HT1A receptors. PMID- 7884483 TI - Surround inhibition among projection neurons is weak or nonexistent in the rat neostriatum. AB - 1. Antidromic activation of striatal spiny projection neurons by substantia nigra stimulation in vivo did not evoke inhibitory postsynaptic potentials (IPSPs) in the antidromically activated neurons, or in neighboring spiny neurons. 2. More generalized activation of projection cells by stimulation of the efferent pathway in slices did not evoke IPSPs in spiny neurons. Inhibitory mechanisms were operative in these slices, as indicated by the presence of an IPSP component in the orthodromic response to local stimulation. 3. Dual intracellular recordings, obtained from cells located within 50-200 microns of each other in striatal slices also failed to demonstrate any inhibition among striatal spiny cells. Spikes triggered in one spiny neuron by current injection failed to produce any postsynaptic potential in nearby spiny cells at resting or depolarized membrane potentials. Excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the cortex were not affected by spiking of neighboring cells. 4. It is impossible to rule out the presence of inhibition among striatal spiny neurons in all circumstances. However, the absence of demonstrable IPSPs in these experiments argue against the common view that mutual inhibition among spiny neurons is a central organizing principle of striatal function. PMID- 7884484 TI - TTX-resistant NMDA receptor-mediated voltage oscillations in mammalian lumbar motoneurons. AB - 1. Whole cell current-clamp recordings were obtained from tetrodotoxin (TTX) isolated motoneurons in the in vitro neonatal rat spinal cord to examine the effects of N-methyl-D-aspartate (NMDA) receptor activation on membrane voltage. 2. NMDA induced rhythmic membrane voltage oscillations, and injection of current ramps revealed the presence of bistable membrane properties, the base and peak of which corresponded to the base and peak values of the voltage oscillations. 3. Nonlinear motoneuron membrane properties induced by NMDA receptor activation may be well suited to reinforce rhythmic patterns of motor output during certain behaviors such as locomotion. PMID- 7884485 TI - [Functional cerebral neuro-imaging at 1.5 Tesla. The results of visual, sensorimotor and auditory stimulations]. AB - Functional activation of the cerebral cortex can be observed with a standard 1.5 Tesla MRI magnet. We used a repeated FLASH 2D one-section sequence with a long echo (TE = 60 ms) and a small passing band. Modification of regional cerebral oxygenation due to neurone activation seems to be the main source of contrast. Sensorimotor stimulation was effected by an unusual mobilization of the fingers. Visual stimulation was performed by intermittent lightings at a frequency of 8 Hz. Auditory stimulation relied on listening to speech sounds. Signal increases were localized on the cerebral cortex with precise anatomico-functional correlation. Using a clinical 1.5 Tesla magnet requires an adequate treatment of data. Thus, stimulated cerebral activity can be portrayed by MRI therapy opening a new way for anatomico-functional cerebral studies. PMID- 7884486 TI - MR imaging of spondylitis with gadopentetate dimeglumine enhancement. AB - MR images of 17 patients with spondylitis were reviewed. T1 weighted spin-echo scans were obtained in 17 patients and proton density and T2 weighted scans were obtained in 15 patients. Unenhanced and gadopentetate dimeglumine enhanced scans were obtained in all patients. Five patients had pyogenic spondylitis, two patients tuberculous spondylitis, two patients fungal spondylitis and eight patients postoperative spondylitis. The four criteria described by Thrush and Enzmann were generally applicable in our study: 1) narrowing of the intervertebral disc; 2) cortical bone erosion; 3) abnormal signal in the adjacent vertebral bodies and 4) abnormal paraspinous or epidural soft tissue. In addition to plain sagittal T1 and T2 weighted images we suggest the routine administration of gadopentetate dimeglumine to assess the extent of the soft tissue mass and to differentiate postoperative spondylitis from a normal postoperative course, by showing disc enhancement. Disc enhancement occurs infrequently in the normal postoperative course. If it is associated with adjacent vertebral bone marrow changes it should be considered as postoperative spondylitis. A differential diagnosis between pyogenic, tuberculous, fungal and postoperative spondylitis was not possible although the pattern of enhancement in tuberculous spondylitis was different from the other cases of spondylitis. PMID- 7884488 TI - Spinal intradural extramedullary enterogenous cysts. Report of two cases and review of literature. AB - Two patients with intradural extramedullary cysts of the spinal canal are described. Both presented with slowly progressive myelo-radiculopathy caused by mucin-producing epithelial-lined cysts in cervical and upper thoracic region. Histologically, both lesions were considered to be neurenteric cysts with an endodermal origin. Radiographic diagnosis was made by a combination of myelography, computed tomographic scan with myelography (CTM), and magnetic resonance imaging (MRI). Complete surgical resection was curative in both cases. Clinical presentation, histological characteristics, imaging findings and surgical management of this rare lesion are highlighted. PMID- 7884487 TI - [The role of magnetic resonance angiography in the follow-up of intracranial arteriovenous malformations treated by an intravascular approach]. AB - The purpose of our work was to measure the accuracy and reliability of MR Angiography in the study and follow-up of intracranial arteriovenous malformations, and in particular to evaluate the results of endovascular treatment. Over an 18-month period 4 patients with such malformations were examined by MR-Angiography. There was an angioma of the corpus callosum, a left parieto-rolandic angioma, a posterior thalamic angioma and a cerebellar angioma. All examinations were performed with a Magneton-Impact 1 Tesla machine (Siemens, Erlangen, Germany), using a head coil, MR-Angiography with time-of-flight sequences and differential arterial and venous saturations. Each patient was examined by MR-Angiography first at the beginning of treatment, then when ambulatory after embolization. The morphological study applied to the afferent vessels, the nidus and the efferent veins. MR-Angiography proved to be very good in identifying the arteries feeding the malformation, and this made it easier to evaluate the reduction of their input after treatment, without having recourse to any arteriography. Beside, analysis of the nidus was facilitated by the judicious arrangement of arterial and venous saturations. In fact, the systematic use of MR Angiography in the follow-up of intracranial arteriovenous malformations makes it possible to measure, with full reliability, the efficacy of the endovascular treatment under conditions of comfort unequalled in these out-patients, and selective angiography sequences need to be performed only during therapeutic phases. PMID- 7884489 TI - Post-traumatic cerebral air embolism. Case report. AB - A case of post-traumatic cerebral air embolism is presented. In the chest-X radiography fractures of many ribs and hemo-pneumothorax were visible on the right side associated with intra-alveolar, interstitial hemorrhages and mediastinal emphysema. At the end of a CT scan of the head appeared features of arterial air embolism. The patient was diagnosed as brain dead and cardiac arrest occurred one hour after. PMID- 7884490 TI - Iatrogenic spinal epidermoid tumour associated with tuberous sclerosis. A diagnostic pitfall. AB - We present a case of spinal epidermoid tumour that was probably caused by lumbar punctures. The tumour was detected on MRI in a child with tuberous sclerosis complaining of atypical low back pain. Preoperatively the tumour was considered to be a cystic astrocytoma of ependymoma of the conus terminalis. The association of tuberous sclerosis with a spinal tumour is rare but has been recorded in the literature. The diagnosis was an epidermoid tumour (E.T.). The MRI appearances were unusual for a spinal ET: the signal intensity changes were different from those reported in the literature and the presence of calcification and cavitation has not yet been reported. This case represents a diagnostic pitfall, since both entities were unrelated. PMID- 7884491 TI - Society sues NRC over radiopharmacy rule. PMID- 7884492 TI - Nuclear medicine researchers scale to new heights. PMID- 7884493 TI - Reimbursement proposals aim to put more money in physicians' pockets. PMID- 7884494 TI - Cerebral perfusion imaging tracers for SPECT: which one to choose? PMID- 7884495 TI - Lung scan evaluation of thrombolytic therapy for pulmonary embolism. AB - Data from three trials of thrombolytic therapy for pulmonary embolism (PE) were combined to assess the utility of perfusion lung scan defect scoring in predicting the response to thrombolytic therapy. METHODS: Pre- and post-therapy lung scans and duration of symptoms were available for a total of 221 patients, 167 were treated with various thrombolytic regimes and 54 were treated with heparin alone. RESULTS: Improvement in the lung scan defect score was correlated with larger initial defect score (r = 0.53), segmental appearance (r = 0.31) and shorter duration of symptoms (r = 0.20). There was no significant residual correlation between improvement and segmental appearance in a multiple regression analysis after accounting for initial defect score and duration of symptoms. Two lung scan scoring methods (segmental and anterior-posterior method) provided similar results with low interobserver variability (r = 0.90 for both methods). CONCLUSION: This study indicates that the baseline perfusion lung scan defect severity helps to predict the response to thrombolytic therapy. PMID- 7884496 TI - Defining a role for thrombolytic therapy in the management of pulmonary embolism. PMID- 7884497 TI - Measurement of regional pulmonary blood flow with PET. AB - We have previously reported a method for measuring regional pulmonary blood flow (PBF) in experimental animals using 15O-water and PET. The method requires withdrawing blood from the pulmonary artery during the PET scan, so that the input function can be estimated for the one-compartment model used to analyze the data. The purpose of the present study was to modify and validate this technique for a more general use in humans. METHODS: PBF was measured after injections of 15O-water in 15 normal subjects and in five patients with reduced cardiac output. In ten of the normal subjects, PBF was also measured after the injection of 68Ga albumin macroaggregates (MAA). In the five other normal subjects and in the cardiomyopathy patients, PBF was measured twice after two separate 15O-water administrations. The input function was estimated from a region of interest (ROI) over the right ventricle (RV), with corrections when necessary, for time delays between RV and lung tissue. RESULTS: The mean value for PBF in the normal subjects was 121 +/- 32 ml/min/100 ml lung, and was 57 +/- 33 ml/min/100 ml lung in the patients with cardiomyopathy. The correlation between PBF measured with 15O-water and PBF measured with 68Ga-MAA was r = 0.96. There was no significant difference in the mean value for PBF or the ventral-dorsal distribution of PBF when sequential measurements were made in the same individual. PBF increased in general in the ventral-dorsal direction in these supine subjects, although PBF was more evenly distributed in the cardiomyopathy patients. CONCLUSION: Measurement of regional PBF with 15O-water and PET appears to be a valid, noninvasive approach for evaluating the pulmonary perfusion pattern of humans. PMID- 7884498 TI - Assessment of disease severity in parkinsonism with fluorine-18 fluorodeoxyglucose and PET. AB - Fluorine-18-fluorodeoxyglucose (FDG) and PET have been used to identify an abnormal regional metabolic covariance pattern in Parkinson's disease (PD). To examine the potential use of this covariance pattern as a metabolic imaging marker for PD, we describe the Topographic Profile Rating (TPR), which is a method for calculating subject scores for this pattern in individual PD patients. We then assess the relationship between these metabolic measures and objective independent disease severity ratings. METHODS: Two independent groups of PD patients were studied with FDG-PET. Group A consisted of 23 patients (mean age 60.2 +/- 12.2; mean Hoehn and Yahr stages 2.4 +/- 1.3) and Group B had 14 patients (mean age 49.0 +/- 12.1; mean Hoehn and Yahr stage 3.2 +/- 1.2). The regional cerebral metabolic rates for glucose (rCMRGlc) in all patients in each group were measured. TPR was used to calculate subject scores for the disease related covariance pattern on a patient-by-patient basis. RESULTS: In both PD patient groups, subject scores correlated with Hoehn and Yahr disease severity ratings (Group A: r = 0.59, p < 0.004; Group B: 0.57, p < 0.04), quantitative ratings for bradykinesia (Group A: r = 0.63, p < 0.002; Group B: r = 0.61, p < 0.03), rigidity (Group A: r = 0.59, p < 0.004; Group B: r = 0.59, p < 0.04), but not with tremor. CONCLUSION: These findings indicate that regional metabolic covariance patterns are robust imaging markers of disease severity. FDG-PET may be useful clinically in assessing parkinsonian disability and disease progression. PMID- 7884499 TI - Regional analysis of D2 dopamine receptors in Parkinson's disease using SPECT and iodine-123-iodobenzamide. AB - The goal of this study was to examine the relationship between D2 dopamine receptor density and levodopa dosage, disease duration and dyskinesia in Parkinson's disease (PD). METHODS: Iodine-123-iodobenzamide SPECT scans were obtained from 14 PD patients and 12 age-matched controls using a three-headed camera in conjunction with MRI and a fiducial-based image registration system to define regions of interest. Basal ganglia/cerebellum counts/voxel ratios in dorsal and ventral head of caudate and anterior and posterior putamen were measured at 30, 60, 120 and 180 min postinjection. As in 11C-raclopride studies, ratios obtained at that time when they asymptomatically approach a maximum value (180 min) were accepted as the best measure of receptor density. RESULTS: Among PD patients, a trend towards an inverse correlation between regional basal ganglia/cerebellum ratios and levodopa dosage achieved significance in ventral caudate (F = 6.244, p = 0.037); similarly, an inverse correlation between these ratios and disease duration achieved significance in anterior putamen (F = 13.144, p = 0.007). Ratios were significantly lower in anterior putamen in patients with dyskinesia (t = 3.068, p = 0.042). CONCLUSION: In PD, the previously observed inverse correlation between levodopa dosage and D2-receptor density appears to be most prominent in the least dopamine-depleted region, ventral caudate. There may be a genuine effect of disease duration on receptor density in putamen and reduced receptor density in anterior putamen may be associated with dyskinesia. PMID- 7884500 TI - Technetium-99m-HMPAO SPECT cerebral blood flow study in children with craniosynostosis. AB - Premature closure of cranial sutures (primary craniosynostosis) in children leads to characteristic skull deformities and prevents the constricted brain from growing normally. Although the cause remains unknown, several etiological factors have been cited. Recently, hypovascularity has been reported as a possible cause of craniosynostosis. METHODS: In a prospective study regional cerebral blood flow studies were carried out with 99mTc-HMPAO SPECT in seven children with craniosynostoses. Five preoperative and six postoperative studies were conducted and the results correlated with radiological and surgical findings. RESULTS: Preoperative studies revealed regional hypovascularity in the underlying cerebral hemisphere, corresponding to the fused sutures. Postoperative studies revealed disappearance of these perfusion defects in most cases, indicating normalization of perfusion following surgical decompression. CONCLUSION: This study establishes the presence of cerebral hypovascularity in craniosynostoses and suggests that early surgery and release of craniostenosis is essential to achieve optimum perfusion and brain development. PMID- 7884501 TI - Crossed cerebellar diaschisis: analysis of iodine-123-IMP SPECT imaging. AB - The aim of this study was to review the etiology of CCD and study factors that affect the development and manifestation of CCD. METHODS: Three hundred and eleven patients with supratentorial lesions were evaluated for the presence of CCD with SPECT and 123I-IMP. In representative cases, continuous arterial blood sampling was done and rCBF was calculated using Kuhl's method. RESULTS: IMP-SPECT detected an abnormality in 206 patients, of whom 30 had CCD. Of CCD patients, 27 had more than single lobe involvement, 17 had motor impairment, 8 of 11 had rCBF of less than 29.1 +/- 10.9 ml/100 g/min. There was also a significant difference in rCBF between non-CCD and CCD cases. CONCLUSION: Although CCD can also occur with dementia (mixed or vascular type), it is more common with multilobar lesions. It is also associated with the presence of motor impairment but not related to its severity. It is more likely to develop, however, if rCBF is less than 29.1 +/- 10.9 ml/100 g/min regardless of etiology. PMID- 7884502 TI - Somatostatin receptor scintigraphy in central nervous system tumors: role of blood-brain barrier permeability. AB - Somatostatin receptors are expressed in meningiomas and low-grade gliomas, raising the hope that scintigraphy with 111In-DTPA-D-Phe1-octreotide might be helpful in the in vivo localization, differential diagnosis and postoperative/postradiotherapy brain tumor follow-up. METHODS: Indium-111-DTPA-D Phe1-octreotide scintigraphy and brain scintigraphy using 99mTc-DTPA as a nonspecific tracer for blood-brain barrier integrity were simultaneously performed in 60 patients with CNS tumors using dual-isotope acquisition mode SPECT. For 23 patients, the scintigraphic findings were also compared with in vitro somatostatin receptor autoradiography of surgical biopsy specimens. RESULTS: In meningiomas (located outside the blood-brain barrier), the somatostatin receptor scan showed all tumors and scintigraphic signal intensity correlating with in vitro SSR density positive in all meningiomas. Less contrast was seen on 99mTc-DTPA scans. In all tumors inside the blood-brain barrier, the 111In-DTPA-D-Phe1-octreotide scan visualized the tumors with a disrupted blood brain barrier, as seen by 99mTc-DTPA scintigraphy. Discrepancies, however, were observed between somatostatin receptor scintigraphy and in vitro receptor autoradiography. CONCLUSION: Combined somatostatin receptor and 99mTc-DTPA scintigraphy may be helpful for noninvasive differentiation between meningiomas and other CNS tumors. False-negative scans were observed as a result of shielding by the intact blood-brain barrier. Interpretation of negative and positive somatostatin receptor scans in CNS tumors must therefore be done with caution. PMID- 7884503 TI - In vivo protein synthesis rate determination in primary or recurrent brain tumors using L-[1-11C]-tyrosine and PET. AB - The applicability of protein synthesis rate (PSR) determination with L-[1 11C]tyrosine (11C-TYR) and PET was assessed in patients suspected of a primary or recurrent brain tumor. METHODS: Simultaneous to intravenous injection of 265 MBq of 11C-TYR, dynamic PET acquisition was started and continued for 50 min. Arterial samples were taken and analyzed for 11C-TYR and metabolites. Based on this data, a model was proposed and the corresponding PSR calculated. RESULTS: Plasma metabolites were 11CO2, 11C-proteins and 11C-L-DOPA, constituting more than 50% of total plasma radioactivity at 40 min postinjection. Plasma 11CO2 reached a plateau of around 25% of total plasma radioactivity at 20 min postinjection. Plasma 11C-protein was not detected before 10 min postinjection, but increased exponentially afterwards to 20% at 40 min postinjection. Plasma 11C L-DOPA was the only acid-soluble radioactive metabolite detected and was less than 8% at 40 min postinjection. Using a five-compartment model, it was shown that while the net PSR was dependent on the recycling of amino acids from protein, the amino acid incorporation was not, which was thus used for subsequent analysis. It was found that our curve-fitting results were unreliable due to the exchange of 11C-TYR between plasma and erythrocytes whereas the graphical Patlak Gjedde analysis is hardly influenced by this transport phenomenon. The average amino acid incorporation rate thus calculated was 0.7 nmole/ml.min for nontumor tissue with a tumor versus nontumor average ratio of 1.7. CONCLUSION: The assessment of the PSR with TYR-PET is valuable and relatively simple to implement clinically. PMID- 7884504 TI - Radiolabeled chimeric anti-CEA monoclonal antibody compared with the original mouse monoclonal antibody for surgically treated colorectal carcinoma. AB - Biodistribution and tumor uptake of a chimeric human-mouse monoclonal antibody (MAb) and the original mouse MAb have been comparatively studied. METHODS: Eighteen patients with suspected colorectal cancer scheduled for surgery underwent immunoscintigraphy with 123I-labeled chimeric anti-CEA MAb. Iodine-125 and 131I trace-labeled chimeric and original mouse MAb were simultaneously injected for biodistribution studies. RESULTS: Similar serum kinetics and a low immunogenicity were observed for both antibodies. Mean binding capacity to CEA measured in PBS after radiolabeling was identical for both MAbs and it was slightly decreased when measured in serum 1-4 hr after injection. Radiochromatograms of patients sera showed immune complex formation related to the amount of circulating CEA. Postoperative ex vivo radioactivity counting in tissue samples revealed similar antibody distributions with notably similar antibody uptakes in tumors. High tumor uptakes (between 0.02 to 0.06% injected dose per g) were observed in 3 of 13 patients operated for primary or metastatic colorectal cancer. CONCLUSION: In this dual-label technique, the radioiodinated anti-CEA IgG4 chimeric MAb and the original mouse IgG1 MAb were shown to have very similar behavior in colorectal cancer patients. PMID- 7884505 TI - Comparison of complete versus fragmented technetium-99m-labeled anti-CEA monoclonal antibodies for immunoscintigraphy in colorectal cancer. AB - The goal of this study was to intraindividually compare complete versus fragmented directly labeled 99mTc monoclonal anti-CEA antibody with respect to antigen targeting and tumor uptake kinetics, sensitivity and diagnostic accuracy in colorectal cancer patients. METHODS: Twenty-five patients were investigated with 99mTc-labeled anti-CEA IgG1 BW 431/26 and the F(ab')2/Fab' fragment mixture F023C5 within 7 days. For quantitative analysis, an ROI technique was applied to planar scans, whole-body scans and SPECT slices 10 min to 48 hr postinjection. Final correlations were performed according to histology after surgery or biopsy. RESULTS: Earliest tumor detection with complete IgG1 was possible 4 hr postinjection (52% of finally positive lesions); imaging at 24 hr or even 48 hr was necessary in 48%. Tumor detection with fragments was possible in 17% at 1 hr postinjection and in 94% at 4 hr postinjection. In 35%, SPECT was necessary for tumor detection with both MAbs. Absolute antibody uptake in tumor lesions was higher with complete MAbs than with fragments. CONCLUSIONS: Lesions known for their good vascularization, vascular permeability and antigen accessibility were detected earlier and with higher sensitivity with fragments than with complete MAbs due to faster background clearance despite lower absolute antibody uptake. PMID- 7884506 TI - Iodine-131 therapy of hyperthyroidism in pediatric patients. AB - The purpose of this retrospective study was to evaluate the utility of 131I as therapy for hyperthyroidism in children and to evaluate its short-term side effects. METHODS: The results of 131I therapy of hyperthyroidism were evaluated in a group of 35 pediatric patients. RESULTS: In 29 patients propylthiouracil or methimazole therapy was abandoned due to noncompliance (13), relapse or failure to control hyperthyroidism (13), vasculitis (1), neutropenia (1) or a lupus-like syndrome (1). Average treatment activity was 7.7 +/- 2.9 (s.d.) mCi, corresponding to 0.16 +/- 0.03 mCi/g. Thirty patients (86%) received a single radioiodine treatment and five (14%) were retreated. In patients who became hypothyroid after a single dose, hypothyroidism was noted within 100 days of treatment. Clinical management problems included vomiting in four patients and enuresis in four patients. Mild radiation thyroiditis occurred in one patient and nodularity was noted after therapy in two patients. CONCLUSION: Iodine-131 is effective for both initial treatment of hyperthyroidism and the treatment of medical treatment failures in pediatric patients. Awareness of vomiting and enuresis as potential management problems is crucial when using 131I in this age group. Therefore, special treatment precautions may be required. PMID- 7884507 TI - Gallium-67 scintigraphy in lymphoma with bone involvement. AB - Both Hodgkin's and non-Hodgkin's lymphoma (NHL) may involve bone. Traditionally, 99mTc-MDP bone scintigraphy has been used to detect such involvement. In recent years, 67Ga scintigraphy has shown to be useful in monitoring treatment response in lymphoma. Although 99mTc-MDP has not been found particularly useful for monitoring bone response to cancer treatment, we were interested in whether 67Ga scintigraphy and SPECT could be used to monitor bone involvement with lymphoma. METHODS: Gallium-67 and 99mTc-MDP uptake were investigated in 20 patients with lymphoma involving the bone before treatment. Gallium-67 scans were done in 16 patients for monitoring response to treatment in the bone lesions. RESULTS: Gallium-67 studies diagnosed bone lesions in 19 of the 20 patients. Technetium 99m-MDP detected bone lesions in all patients investigated. In four patients, uptake by Ga-67 was more intense than 99mTc-MDP and in another four patients 99mTc-MDP uptake was more evident. Gallium-67, however, was useful in detecting other regions of involvement in 18 of the 19 patients with soft-tissue lymphoma lesions. Gallium-67 scintigraphy also correctly monitored bone response to treatment in all but one of the 16 patients who had 67Ga scintigraphy after completing therapy. CONCLUSION: Gallium-67 uptake by lymphoma involving the bone can be used to monitor osseous response to treatment. PMID- 7884508 TI - Esophageal hypomotility in primary and secondary Raynaud's phenomenon: comparison of esophageal scintigraphy with manometry. AB - Esophageal motility was assessed by manometry and scintigraphy in 25 patients with primary Raynaud's phenomenon and 24 patients with secondary Raynaud's phenomenon as part of a connective tissue disorder. METHODS: For each scintigraphic study, transit time was evaluated after three separate swallows. Scintigraphy was abnormal if transit time was longer than 15 sec for two or three measurements. RESULTS: In the case of primary Raynaud's phenomenon, manometry was normal in 24 of 25 patients. A similar ratio was found with scintigraphy. In the case of secondary Raynaud's phenomenon manometry was abnormal in 15 of 24 patients, while scintigraphy was abnormal in 13 of 24 patients. Considering manometry as gold standard, overall sensitivity of scintigraphy was 86%, specificity 89%, positive predictive value 75% and negative predictive value 94%. CONCLUSION: Esophageal dysfunction is common in patients with connective tissue disorders but rare in patients with primary Raynaud's phenomenon. Esophageal scintigraphy is a useful noninvasive initial screening test for esophageal dysfunction in patients with Raynaud's phenomenon. PMID- 7884509 TI - Myocardial glucose metabolism in noninsulin-dependent diabetes mellitus patients evaluated by FDG-PET. AB - Diabetes mellitus (DM) is one of several factors influencing the assessment of myocardial viability using fluorine-18 fluorodeoxyglucose (FDG) PET. METHODS: To compare the myocardial glucose metabolism of normal subjects to patients with DM, we performed a quantitative FDG study during insulin clamp, oral glucose loading and fasting in nine normal volunteers and eight patients with noninsulin dependent DM (NIDDM). RESULTS: During oral glucose loading, myocardium-to background (MB) ratio remarkably deteriorated in NIDDM patients compared with normals because of high plasma glucose and low serum insulin. Myocardial glucose utilization (MGU) rates in NIDDM patients were also lower than those in normal volunteers. MB ratio of FDG remarkably improved with insulin clamp in NIDDM patients compared with oral glucose loading. MGU rates during insulin clamp were still slightly lower than in the normal volunteers despite low plasma glucose and adequate plasma insulin. CONCLUSION: The insulin clamp method may be very useful in NIDDM patients for improved myocardial FDG uptake compared to oral glucose loading or fasting, but slight decreases in MGU rates during insulin clamp in NIDDM patients may be because of insulin resistance (GluT4 abnormality). PMID- 7884510 TI - Osseous and central nervous system sarcoidosis: scintigraphic and radiographic findings. AB - We present a case of painful osseous sarcoid involving the tibiae bilaterally. Lesions were initially found on plain radiographs and on a 99mTc-MDP bone scan. The patient was also found to have CNS involvement of sarcoidosis in the form of diabetes insipidus and panhypopituitarism. CNS lesions were demonstrated on CT and MR images. PMID- 7884511 TI - Scintigraphic pitfalls in giant parathyroid glands. AB - We report a case of hyperparathyroidism with surgically confirmed bilaterally enlarged parathyroid glands mimicking a normal thyroid gland. Technetium-99m pertechnetate-201Tl chloride subtraction scintigraphy was inconclusive because of suppressed thyroidal [99mTc]pertechnetate uptake after coronary angiography. Technetium-99m-sestamibi double-phase scintigraphy showed homogeneous 99mTc sestamibi uptake that mimicked a normal thyroid gland and no differential washout, thus leading to an erroneous visual interpretation of a normal scan. Semiquantitative assessment of tracer washout, however, can differentiate between normal thyroid tissue and symmetrical parathyroid uptake mimicking normal thyroid tissue. We conclude that semiquantitative assessment of tracer washout increases the diagnostic sensitivity of 99mTc-sestamibi double-phase scintigraphy if: (a) the interpreter is unaware of the anatomical situation, (b) the scintigraphic delineation of the thyroid is hampered by a blocked tracer uptake or (c) the visual interpretation reveals no differential washout in the neck region. PMID- 7884512 TI - Reversible hypoperfusion of the cerebral cortex in normal-pressure hydrocephalus on technetium-99m-HMPAO brain SPECT images after shunt operation. AB - A man with dementia underwent radionuclide cisternography to establish the diagnosis of communicating hydrocephalus. Technetium-99m-HMPAO brain SPECT images showed marked hypoperfusion of both posterior cerebral cortices and three dimensional displays that demonstrated perfusion defects at both of the posterior parietotemporal regions. A successful ventriculoperitoneal shunt operation was performed. Five and one-half months later, repeat three-dimensional display showed that the perfusion defects had resolved and a repeat brain SPECT image showed marked improvement of the hypoperfusion. This concurred with postoperative clinical improvement. Technetium-99m-HMPAO brain SPECT, which provides objective documentation of clinical recovery after surgery, could be routinely used to evaluate patients with normal-pressure hydrocephalus. PMID- 7884513 TI - Absent uptake on hepatobiliary scintigraphy in hepatic lobar infarction from portal vein occlusion in cholangiocarcinoma. AB - Hepatic infarction is an uncommon entity because of the dual blood supply to the liver. We report a case in which multimodalities demonstrate infarction of the left lobe of the liver secondary to left portal vein occlusion by an invasive cholangiocarcinoma. A 99mTc-DISIDA hepatobiliary scan showed complete absence of activity to the left of the gallbladder fossa. The differential diagnosis of absent hepatic activity on a hepatobiliary scan must include hepatic infarction. PMID- 7884514 TI - Myocardial technetium-99m-teboroxime uptake during adenosine-induced hyperemia in dogs with either a critical or mild coronary stenosis: comparison to thallium-201 and regional blood flow. AB - Experimental studies have shown 99mTc-teboroxime to have a higher first-pass myocardial extraction, exceeding that of 201Tl with nearly linear initial myocardial uptake over a wide range of coronary flows. The goal of this study was to quantitatively compare teboroxime with 201Tl for the assessment of a regional coronary flow imbalance when administered during adenosine vasodilation in dogs with either critical or mild LAD stenoses. METHODS: Twenty-four anesthetized dogs with either critical (n = 10) or mild (n = 14) LAD stenoses were given an i.v. infusion of adenosine (300 micrograms/kg/min). When LCx flow was maximal, 201Tl, teboroxime and microspheres were simultaneously injected and the dogs were killed either 2 or 4 min later. Regional 201Tl, teboroxime activities and myocardial blood flow were determined by gamma well counting and ex vivo imaging of 99mTc teboroxime activity in myocardial heart slices was performed. RESULTS: In both the critical and mild stenosis groups, the LAD/LCx zone ratios in dogs killed 2 min after tracer injection for both 201Tl (0.31 +/- 0.07, 0.63 +/- 0.05) and teboroxime (0.38 +/- 0.09, 0.72 +/- 0.04) significantly underestimated the microsphere flow ratio (0.18 +/- 0.05, 0.43 +/- 0.05) (p < or = 0.01), but the degree of underestimation was greater for teboroxime compared with Tl (p < or = 0.05). CONCLUSION: In dogs with either critical or mild LAD stenoses, as early as 2 min after tracer injection, the 201Tl activity ratio more accurately assessed the adenosine-induced regional flow heterogeneity than did teboroxime. These results highlight the importance of an ultra-fast imaging protocol when using teboroxime with pharmacologic stress. PMID- 7884515 TI - Methionine uptake by tumor tissue: a microautoradiographic comparison with FDG. AB - L-methyl-11C-methionine (11C-Met) and 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) are used for tumor diagnosis and treatment evaluation by PET. In order to examine the role of these tracers in cancer imaging, intratumoral properties of 14C-Met were studied and compared to those of 18F-FDG. METHODS: The distribution of 14C Met in various cellular elements of two different mouse malignant tumor tissues, MH134 and FM3A, was analyzed serially using microautoradiography within a period of 120 min after injection of the tracer. RESULTS: Carbon-14-Met and 18F-FDG showed different distributions in tumor tissue. Carbon-14-Met uptake by the tumor was mostly by viable cancer cells. The uptake by macrophages and other cellular components was low. The uptake was higher in the highly proliferative tumor but did not reflect protein synthesis. The rapid and slow growing tumors demonstrated that 14C-Met uptake ratio was lower than that of 18F-FDG, reflecting de novo DNA synthesis ratio. CONCLUSION: Carbon-14-Met uptake represents the presence of viable cancer cells. Carbon-11-Met may be suitable for treatment evaluation of individual tumors but not growth rates of different tumors. Fluorine-18-FDG reflects tumor-host immune system reaction and is an excellent tool for pretreatment evaluation of tumors and determination of tumor proliferative activity. PMID- 7884516 TI - High-resolution PET in cats: application of a clinical camera to experimental studies. AB - A commercial high-resolution scanner designed for clinical PET studies was tested for its applicability to investigate cerebral metabolism and blood flow in cats. METHODS: Cerebral blood flow, CMRO2, CBV and CMRglc were determined repeatedly using 15O steady-state oxygen methods and 18F-fluorodeoxyglucose (FDG). Metabolic and blood flow images of 14 contiguous 3-mm PET slices were compared to histological sections in four control animals. In another six cats, hemodynamic and metabolic changes were followed by serial multi-tracer PET for 24 hr after permanent occlusion of the left middle cerebral artery (MCA). Pattern and extent of changes of the physiological variables were related to the final infarct verified in matched histological sections. RESULTS: At spatial resolutions (FWHM) of 3.6 mm in transaxial planes and 4.0 mm axially, details of the gross anatomy of the cat brain were distinguished best in the FDG images. Cerebral blood flow, CMRO2 and CMRglc values measured in the cortex, white matter and basal ganglia were in the range of common autoradiographic results. Immediately after MCA occlusion, there was widespread decrease in blood flow, but metabolism was preserved at values, which suggest viable tissue. With time, the areas of increased oxygen extraction fraction (OEF) moved from the center to the periphery of the MCA territory. CONCLUSION: High-resolution PET can be used for repeat, quantitative imaging of blood flow and metabolism in small animals such as the cat. After MCA occlusion, the changes in blood flow and metabolism can be followed over time and can be related to the final morphological lesion. PMID- 7884517 TI - Frozen section microautoradiography in the study of radionuclide targeting: application to indium-111-oxine-labeled leukocytes. AB - The microscopic biodistribution of radioactivity in tissues is important in determining microdosimetry. This study addresses the use of frozen section microautoradiography in studying the subcellular distribution of 111In in leukocytes labeled with 111In-oxine. METHODS: In conjunction with frozen section microautoradiography, computer image analysis methods were applied to the analysis and quantification of leukocyte sections and superimposed autoradiographs. Rapid cell fractionation was used to confirm the results. RESULTS: The emulsion (Ilford K2) response was linear over the concentration range investigated (0-33 MBq ml-1). Resolution of radionuclide distribution was better than 2 microns. The autoradiographs showed no dependence of radiolabel uptake on cell type. Classification of all cells into intervals according to grain density suggests an exponential rather than normal distribution, with approximately 50% of cells having little or no radiolabel. In any one sample, cells which were heavily labeled were approximately 10 times more likely to be found in aggregates (60% found in aggregates, mostly neutrophils) than cells which were not heavily labeled (6% found in aggregates); and the grain densities were at least twofold higher over nuclei than over cytoplasm. The last observation was confirmed by the rapid cell fractionation method which showed that approximately 57% of the total radioactivity was bound to nuclei. CONCLUSION: Frozen section microautoradiography is a practical and reliable approach to determining sub-cellular distribution of 111In. The radiolabeling process causes aggregation of neutrophils. Uptake is not significantly dependent on cell type, but only a fraction of cells are appreciably labeled. The radioactive concentration in cell nuclei is at least two-fold higher than in cytoplasm. Microautoradiography can be used to provide distribution data as input into computer models for sub-cellular dosimetry. PMID- 7884518 TI - Attenuation correction in cardiac SPECT without a transmission measurement. AB - The accuracy of SPECT cardiac perfusion imaging is impaired by artifacts induced by nonuniform gamma-ray attenuation. This study proposes a method to estimate attenuation in the chest of patients without the additional hardware and expense of transmission imaging. METHODS: After the standard 201Tl or 99mTc-sestamibi delayed images were obtained, 99mTc macroaggregated albumin (MAA) was injected and dual-energy SPECT acquisition was performed with windows centered at 140 keV and 94 keV. Lung contours were obtained by thresholding the on-peak (140 keV) reconstructions. Outer body contours were defined from images produced by reconstruction of the lower energy scatter window obtained simultaneously at the time of the lung (MAA) imaging. Following assignment of standard attenuation values to the lung and nonlung (soft tissue) regions attenuation correction was achieved by means of a modified iterative Chang algorithm. The results were quantitatively evaluated by imaging of a cardiac phantom filled with uniform activity placed in a chest phantom. Sensitivity to the choice of lung and soft tissue attenuation values, the choice of the threshold used for lung segmentation, and errors in registration of the attenuation map were assessed. RESULTS: Application of this technique in a chest phantom and in patients imaged with both 201Tl and 99mTc-sestamibi resulted in improvement in artifactually decreased inferior wall activity without adversely affecting the other walls. The results were relatively insensitive to choice of values for lung and soft-tissue attenuation, lung thresholding, and small (< or = 1.3 cm) registration errors. CONCLUSION: This simple method corrects for nonuniform attenuation in males; studies are underway to adapt the method to determine breast contour in females and to determine the value of the method in clinical practice. PMID- 7884519 TI - Gallium-67 complexes as radioactive markers to assess gastric and colonic transit. AB - Constipation and gastroparesis are gastrointestinal tract disorders that can be assessed by using radioactive markers in conjunction with scintigraphic techniques. Indium-111-DTPA is the radiopharmaceutical of choice for treating colonic transit in constipated patients, but it is an expensive product and its availability has been unreliable. Indium-113m-DTPA was the tracer used in our study to determine the liquid gastric emptying rate in dual-isotope solid/liquid emptying studies, however, cessation of the 113Sn/113mIn generator production makes it unavailable. Thus, development of alternative tracers to 111In-DTPA and 113mIn-DTPA was essential. METHODS: Gallium-67-citrate and 67-Ga-EDTA were compared to 111In-DTPA to assess their efficacy for exclusive retention in the Gl tract. These markers were orally administered into rats and their three-day cumulative fecal excretion, urine excretion and carcass retention were measured. An in vitro gastric emptying model was used to determine liquid phase partitioning of 113mIn-DTPA, 67Ga-citrate and 67Ga-EDTA at 37 degrees. RESULTS: Gallium-67-citrate was predominantly excreted in the feces (97.2% +/- 0.2%) after three days, with negligible urine excretion (0.1% +/- 0.0%) and carcass retention (0.6% +/- 0.2%). These results are analogous to those obtained for 111In-DTPA for fecal excretion (96.7% +/- 2.6%), urine excretion (0.6% +/- 0.0%) and retention in the carcass (0.2% +/- 0.0%). Gallium-67-EDTA showed similar partitioning in the liquid phase of the gastric emptying model compared with 113mIn-DTPA. CONCLUSION: Gallium-67-citrate is an economical and readily available alternative to 111In-DTPA as a colonic transit radiopharmaceutical. Gallium-67-EDTA is also an alternative to 113mIn-DTPA for assessing liquid-phase emptying in a dual isotope solid/liquid gastric emptying study. PMID- 7884520 TI - Quantitative double-tracer autoradiography with tritium and carbon-14 using imaging plates: application to myocardial metabolic studies in rats. AB - A system for 3H- and 14C-labeled macroautoradiography was developed that is able to quantify the tissue radioactivity of two tracers using imaging plates. METHODS: Discrimination between electrons emitted from 3H and 14C is possible on the basis of their different energy distributions. The general use imaging plate with a protective layer detects 14C radioactivity, but it does not detect 3H radioactivity which has a lower energy distribution than 14C. Recently, a 3H sensitive imaging plate without a protective layer was developed. The 3H distribution image is obtained by subtracting the UR image from the TR image. For quantification of the tissue radioactivity of 3H and 14C, we obtained tissue equivalent values (Bq/mg) of commercially available 3H- and 14C-labeled graded standards using different dilutions of labeled heart paste and liquid scintillation counting. Using the 3H- and 14C-labeled graded standards, we confirmed the validity of the quantification of the 3H-autoradiographic intensity using this subtraction method. We applied this method to a rat model of acute myocardial ischemia to compare regional myocardial free fatty acid uptake determined by beta-methyl[1-14C]heptadecanoic acid to glucose uptake determined by 2-deoxy-D-[1-3H]glucose. RESULTS: Free fatty acid uptake was decreased sharply at the ischemic periphery where glucose uptake was preserved. CONCLUSION: This double-tracer autoradiography with 3H and 14C which has high sensitivity, a high spatial resolution of 50 microns and superior linearity with a wide dynamic range of 10(4) to 10(5) allows accurate quantification of the tissue radioactivity of the two radiopharmaceuticals. PMID- 7884522 TI - Tort law. Selected causes of action beyond professional negligence. PMID- 7884521 TI - Simplified multidose preparation of iodine-123-beta-CIT: a marker for dopamine transporters. AB - Iodine-123-beta-CIT is a SPECT radioligand for dopamine and 5-HT transporters with potential use in Parkinson's disease, schizophrenia and cocaine addiction studies. At present, preparation of no-carrier-added (NCA) [123I] beta-CIT is achieved by iododestannylation of a trialkylstannyl precursor with sodium [123I]iodide in the presence of oxidizing agent, followed by preparative HPLC. The purpose of this study was to develop a faster and simpler method for the routine preparation of this radiopharmaceutical. METHODS: Purification of the labeled compound was accomplished by solid phase extraction (SPE) with a C-18 Sep Pak Light cartridge, which removed unreacted iodide, reaction reagents, polar side products and tributylstannyl precursor. The tributylstannyl precursor was preferred as starting material over the trimethylstannyl precursor due to its higher lipophilicity, allowing better separation of the labeled product and precursor. A TLC method was developed to assess the radiochemical purity of the final product. RESULTS: The method produced [123I] beta-CIT in high radiochemical yields (75% +/- 4%), with high radiochemical purity (> or = 98%) and specific activity (> 67000 Ci/mmole), in 1.5 hr. The final formulation was sterile and pyrogen free. CONCLUSION: The results obtained by solid phase extraction are consistent with those obtained by the HPLC method; with the advantage that the SPE method does not require solvent extraction, evaporation under reduced pressure or HPLC purification. PMID- 7884523 TI - Using a Standard Staffing Index to allocate nursing staff. AB - The Standard Staffing Index (SSI) was established as a method to determine unit staffing needs and allocate staff effectively. Daily staffing is based on the SSI, the average patient acuity, and the unit census. This has resulted in time savings to determine staffing needs and accurate monitoring of staffing patterns and productivity by nurse managers. The SSI is based on specific patient needs as determined by regular evaluations and audits. PMID- 7884524 TI - Flipping assumptions and revisioning perioperative services. AB - As we approach a fully capitated healthcare environment, total revisioning and restructuring of hospitals as a whole, and perioperative services in particular, will be necessary to maintain the financial viability of our healthcare institutions. Nurse executives will be in pivotal roles in leading and influencing these hospital initiatives. The authors present a vision of the new hospital and discuss methods of responding to change within the healthcare environment, with an emphasis on perioperative services. An analysis of the findings of an operating room survey conducted with nurse executives is included in the discussion. PMID- 7884525 TI - The impact of healthcare reform on rural home health agencies. Issues and responses. AB - Healthcare reform will have an impact on home health services, but the extent of change depends on which elements are legislated. The author discusses major issues of reform related to rural home health agencies. Several proactive strategies are recommended, including staffing for a community-based care model, linkages with health providers and community agencies, and political agendas to direct local, state, and national policies related to rural home health services. PMID- 7884526 TI - Assessing the outcomes of professional practice redesign. Impact on staff nurse perceptions. AB - There are many reports in the literature of management innovations to redesign nursing roles and care delivery systems in response to the dramatic changes taking place in the healthcare environment. Few of these innovations have been evaluated systematically in terms of the dynamics and effects of change at the work group level. The authors present results of a longitudinal study evaluating the work group outcomes of a professional practice model implemented in an academic medical center. The strategy of integrating ongoing data collection and feedback into a process of continuous change also are presented. PMID- 7884527 TI - Integrating the Russian emigre nurse into U.S. nursing. AB - To meet the challenges of nursing's agenda for healthcare reform, the nursing profession and schools of nursing must recruit and retain nurses who reflect the diversity of the client population they will serve. With the opening of the former Soviet Union to emigration in 1988, Russian emigres are entering this country in increasing numbers. Many of these newcomers are Russian trained nurses with bicultural sensitivity and Russian language skills who do not possess the skills to practice in the United States. The author describes a tri-institutional project that focused on the design, implementation, and evaluation of a unique training project that prepares Russian nurse emigres for employment in the U.S. healthcare industry. PMID- 7884528 TI - Workplace deviance among nurses. The influence of work group norms on drug diversion and/or use. AB - This analysis attempts to integrate sociological and nursing perspectives regarding on-the-job drug theft and/or use by nurses. Specifically, it uses interview data, collected from 25 practicing nurses, to illustrate the link between work group norms and these forms of nursing deviance. These data suggest that informal work group norms often differ from formalized administrative guidelines. Under these circumstances, work group norms consistently take precedence and thus, serve to shape nurses' behaviors. PMID- 7884529 TI - Job sharing as a part-time employment alternative. PMID- 7884530 TI - Layoff survivor sickness. Minimizing the sequelae of organizational transformation. AB - In 1991, our University Hospital initiated a series of strategic changes designed to increase organizational effectiveness and efficiency, foster a culture of commitment to customer-driven service, and flatten the organizational structure, pushing decision making closer to the point of service. These events, although proactive and positive in their intent, triggered a significant, debilitating response among many members of the nursing staff. The authors discuss the experience of this organization, examines the process of transition and the responses of staff members to change, and provides recommendations for minimizing the sequelae of organizational transformation. PMID- 7884531 TI - Rewarding staff nurse preceptors. AB - Using clinical facility staff members to act as preceptors for senior students can provide multiple advantages; however, this process is labor intensive for staff nurses. The authors describe a survey of staff nurse and nurse manager perceptions of preceptor rewards. There were two statistically significant findings--a special dinner honoring the preceptors and a gift from the student. Anecdotal comments provided useful information. Namely, ongoing feedback between faculty and preceptor about the preceptor's effectiveness was seen as critical. Faculty consultation with unit projects, research, and continuing education programs provided by the faculty also were highly rated. PMID- 7884532 TI - Nursing service and nursing education. Working together in Norway. PMID- 7884533 TI - Modern applications for an ancient bean: soybeans and the prevention and treatment of chronic disease. AB - Soybeans have played an integral part in Asian culture, both as a food and as a medicine, for many centuries. In the West, soybeans are best known for their protein content but increasingly, soyfoods are being recognized as having potential roles in the prevention and treatment of chronic diseases, most notably cancer and heart disease. There are also potential roles for soyfoods with respect to osteoporosis and kidney disease. Although more research is needed, the existing database on the health effects of soyfood intake is quite extensive and clearly warrants greater recognition by the research and clinical communities. Given the ease with which soyfoods can be incorporated into the diet, be it via the traditional soyfoods such as tofu and soymilk, or the more modern soy protein products, such as soy isolates, concentrates and flours, soyfoods may be able to have a significant beneficial impact on public health. PMID- 7884534 TI - 1st International Symposium on the Role of Soy in Preventing and Treating Chronic Disease. Symposium proceedings. Mesa, Arizona, February 20-23, 1994. PMID- 7884535 TI - Traditional soyfoods: processing and products. AB - Although soyfoods have been consumed for more than 1000 years, only for the past 15 years have they made an inroad into Western cultures and diets. Soyfoods are typically divided into two categories: nonfermented and fermented. Traditional nonfermented soyfoods include fresh green soybeans, whole dry soybeans, soy nuts, soy sprouts, whole-fat soy flour, soymilk and soymilk products, tofu, okara and yuba. Traditional fermented soyfoods include tempeh, miso, soy sauces, natto and fermented tofu and soymilk products. This paper presents a brief overview of processing techniques used in the manufacture of traditional soyfoods. PMID- 7884536 TI - Soy protein products: processing and use. AB - Soy protein products are mainly used as ingredients in formulated foods and seldom are seen by the public. They consist of four broad categories. (1) Most soy proteins are derived from "white flakes," made by dehulling, flaking and defatting soybeans by hexane extraction. These may then be milled into defatted flours or grits containing approximately 50-54% protein; extracted with ethanol or acidic waters to remove flavor compounds and flatulence sugars, producing soy protein concentrates containing 65-70% protein; or processed into soy protein isolates containing 90+% protein by alkali extraction of the protein, removal of fiber by centrifugation and reprecipitation and drying of the protein. (2) Full fat products are made in enzyme-active and in toasted forms. (3) Various dried soyfoods, including soy milk and tofu, are produced. (4) Mixtures of soy proteins with cereals, dried milk or egg fractions, gelatin, stabilizers and emulsifiers are offered for specific baking, whipping, breading and batter applications. Texturized products, resembling meat chunks or bacon chips, are made by extrusion of flours and concentrates or spinning of isolates. Soy protein ingredients are used in compounded foods for their functional properties, including water and fat absorption, emulsification, aeration (whipping) and heat setting and for increasing total protein content and improving the essential amino acids profile. PMID- 7884537 TI - Compositional changes in trypsin inhibitors, phytic acid, saponins and isoflavones related to soybean processing. AB - Soybeans are high in protein but also contain a number of minor constituents traditionally considered to be antinutritional factors. These include trypsin inhibitors, phytic acid, saponins and isoflavones. These compounds are now thought to have beneficial biological effects in the diet, such as lowering blood cholesterol or preventing cancer. Soybean processing changes the content of these minor constituents in various ways. This review discusses the changes in content of trypsin inhibitors, phytic acid, saponins and isoflavones as soybeans are processed into the conventional protein ingredients, flours, concentrates and isolates, as well as some of the traditional Oriental soybean foods. PMID- 7884538 TI - Dietary protein, cholesterol and atherosclerosis: a review of the early history. AB - The first purely nutritional investigation into experimental atherosclerosis was carried out by Ignatowski in 1908. Believing that a toxic metabolite of animal protein led to atherosclerosis, he fed meat to adult rabbits and milk and egg yolk to weanling rabbits and caused atherosclerosis. For the next two decades experimental efforts from many laboratories were directed at determining which, if any, animal protein was the most atherogenic. The discovery in 1912 that dietary cholesterol per se was atherogenic turned attention to fat and cholesterol, eclipsing work on dietary protein. In 1926 Clarkson and Newburgh showed that the amount of cholesterol present in the animal protein they fed was insufficient to be atherogenic, demonstrating that some factor other than lipid determined atherogenicity. In 1940 Meeker and Kesten showed that animal protein (casein) was more atherogenic that plant protein (soy). Carroll and his co workers showed that most proteins of animal origin were more cholesterolemic for rabbits than were proteins of vegetable origin, although there was some overlap. Cholesterol turnover is slower and fecal excretion of cholesterol is reduced in rabbits fed casein as opposed to those fed soy protein. The mechanisms underlying this effect are moot. PMID- 7884539 TI - Soy consumption and cholesterol reduction: review of animal and human studies. AB - Animal proteins such as casein are more hypercholesterolemic than soy protein or other plant proteins when fed to rabbits in low-fat, cholesterol-free, semipurified diets. A casein-amino acid mixture produces a hypercholesterolemia similar to that of casein. This appears to be mainly due to lysine and methionine, although other essential amino acids probably contribute to the effect. Arginine appeared to counteract the hypercholesterolemic effects of other essential amino acids. Soy protein gave a lower level of serum cholesterol in rabbits than did a soy protein-amino acid mixture, suggesting the presence of factors in soy protein that counteract the effects of hypercholesterolemic amino acids. Soy protein is also less hypercholesterolemic than casein in other animal species, particularly when the diet contains cholesterol, and substitution of soy protein for animal protein in the diet reduces the concentration of serum cholesterol in humans. This effect is somewhat variable but is generally greater in hypercholesterolemic than in normocholesterolemic subjects. The differing effects of dietary proteins on serum cholesterol concentrations in humans and in rabbits are primarily due to changes in LDL cholesterol, and the hypercholesterolemia produced by dietary casein is associated with down regulation of hepatic LDL receptors. PMID- 7884540 TI - Soy and cholesterol reduction: clinical experience. AB - A role of vegetable proteins in reducing coronary artery disease risk was postulated as long ago as 1909 in Russia by Ignatowski. The protein hypothesis of atherosclerosis was pursued by many investigators, who studied the possible role of animal vs. vegetable protein in modifying concentrations of plasma lipids and thus cardiovascular disease risk. Over the past 20 y, our research group has examined the potential of a diet based on vegetable protein (in most cases, textured vegetable protein, or TVP) to modify plasma lipid concentrations. Textured products allow administration of a large percentage of protein (up to 50 60% in the product) and are available in a variety of food items. We studied > 1000 patients. An extensive review of the literature indicates that similar findings have been reported by others when administering TVP or TVP-like items to subjects with well-characterized hypercholesterolemia (Fredrickson type II). Data are less consistent for treatment of patients with marginal hypercholesterolemia or hypercholesterolemia already corrected by a standard diet before administration of soy products. The TVP diet, is, however, effective when normolipidemic individuals are made hypercholesterolemic by dietary cholesterol administration. These and other findings suggest that, in man, similar to experimental animals, soy protein may in some way up-regulate LDL receptors depressed by hypercholesterolemia or by dietary cholesterol administration. PMID- 7884541 TI - Overview of proposed mechanisms for the hypocholesterolemic effect of soy. AB - A large body of literature indicates that protein from soybeans reduces blood cholesterol concentrations in experimental animals as well as in humans. The mechanism and component of soy responsible has not been established fully. Some suggest that when soy protein is fed, cholesterol absorption and/or bile acid reabsorption is impaired. This is observed in some animal species, such as rabbits and rats, but not in humans nor when amino acids replace intact soy protein. Others propose that changes in endocrine status, such as alteration in insulin:glucagon ratio and thyroid hormone concentrations, are responsible. The metabolic changes that have been observed on soy protein feeding in a variety of animal models, and in some cases humans, include increased cholesterol synthesis, increased bile acid synthesis (or fecal bile acid excretion), increased apolipoprotein B or E receptor activity and decreased hepatic lipoprotein secretion and cholesterol content, which are associated with an increased clearance of cholesterol from the blood. One hypothesis suggests amino acid composition or proportionality of soy causes changes in cholesterol metabolism (possibly via the endocrine system). Others have proposed that nonprotein components (such as saponins, fiber, phytic acid, minerals and the isoflavones) associated with soy protein affect cholesterol metabolism either directly or indirectly. PMID- 7884542 TI - Cholesterol synthesis and absorption by 2H2O and 18O-cholesterol and hypocholesterolemic effect of soy protein. AB - The kinetic behavior of orally ingested 18O-cholesterol was compared with that of orally ingested 13C5-cholesterol in two normocholesterolemic men and the hypocholesterolemic effect of soy protein was demonstrated in 12 hypercholesterolemic men. Our results indicated no difference in the metabolism of orally ingested 18O- and 13C5-cholesterol. The use of 18O-cholesterol and 13C5 cholesterol also allowed simultaneous estimation of fractional rates of cholesterol synthesis using the 2H2O method, which were calculated to be 5.76 and 8.17%/d for the two normocholesterolemic subjects. The percent reduction in plasma cholesterol levels were found to be greater when the hypercholesterolemic men were placed on a soy protein diet than on an animal protein diet. PMID- 7884543 TI - Soy protein, thyroid regulation and cholesterol metabolism. AB - The effects of dietary protein on plasma cholesterol concentrations are well documented: animal proteins (casein) are hypercholesterolemic compared with plant proteins (soy protein). Although this effect of protein source on plasma cholesterol has been shown in many species, the mechanism is not completely understood. This paper reviews the relationship between dietary protein source and plasma thyroxine concentration. The basic premise is that feeding soy protein lowers plasma cholesterol concentration by causing an increase in plasma thyroxine concentrations. The metabolic changes involving cholesterol that occur when soy protein is fed are discussed. These changes are consistent with changes induced by elevating thyroxine. Data are presented from animal studies showing that feeding soy protein to laboratory animals consistently elevates plasma thyroxine concentrations. Furthermore, this elevation in plasma thyroxine concentrations precedes the change in plasma cholesterol concentrations: a necessary requirement for hypothesizing a causative effect. Possible mechanisms as to how a dietary protein source affects plasma thyroxine are also presented. PMID- 7884544 TI - Biology of atherosclerotic plaque formation: possible role of growth factors in lesion development and the potential impact of soy. AB - The advanced lesions of atherosclerosis occlude the affected artery by increasing the thickness of the intima. The focal thickening of the intima is due to a large increase in smooth muscle cells, formation of new connective tissue matrix by these smooth muscle cells and, in hyperlipidemic individuals, the accumulation of intracellular and extracellular lipid. Additionally, monocytes and T lymphocytes infiltrate the artery wall. Various forms of "injury" may lead to cellular infiltration and proliferation. Localized cellular infiltration of monocytes and T cells may be due to changes in adhesive properties of the endothelial surface, involving the expression of specific adhesion molecules. The directed cell migration and proliferation may represent the cells' response to polypeptide growth factors, acting singly or in concert. These peptide growth factors also modulate matrix synthesis and degradation, angiogenesis, cell-cell adhesion and cellular metabolism, including lipid uptake. In atherosclerosis, growth factors may be delivered by infiltrating cells or by activation of cells within the artery wall. Normally, growth factors and their cell-surface receptors are expressed at low or undetectable levels. Their up-regulation in early and developing atherosclerotic lesions suggests a pathogenic role for these molecules. Increased levels of isoflavonoids, in particular genistein, which are associated with consumption of soy-based diets, inhibit cell adhesion, alter growth factor activity and inhibit cell proliferation involved in lesion formation. PMID- 7884545 TI - Thrombotic mechanisms in atherosclerosis: potential impact of soy proteins. AB - Generally injuries that remove or disrupt the endothelial cells lining blood vessels stimulate formation of vascular lesions composed of smooth muscle cells. One of the first events after such endothelial cell disruption is the generation of thrombin at the site of injury. This leads to platelet activation and thrombus formation. Evidence suggests that thrombus formation may stimulate smooth muscle cell proliferation through the action of any number of factors emanating from the thrombus including platelet- or macrophage-derived factors, platelet-derived growth factor, basic fibroblast growth factor or thrombin. Atherosclerotic plaques continue to grow for many years. The slow indolent process of nondenuding chemical injury of the endothelium and lesion formation may be accelerated periodically by thrombi forming on the lumenal surface at sites of small denuding injuries leading to progressive atherosclerotic disease. Genistein, an isoflavonoid derived from soy products, has been shown to inhibit thrombin formation and platelet activation in vitro in addition to its antigrowth factor activity. Should it have similar actions in vivo, this compound has the potential to affect the progression of atherosclerotic disease by modifying coagulation responses. To assess the potential of genistein as a therapeutic for vascular disease, additional studies will be required to establish its effect on experimental vascular lesion formation. PMID- 7884546 TI - Protective effects of soy protein on the peroxidizability of lipoproteins in cerebrovascular diseases. AB - To study the mechanism of dyslipoproteinemia, lipoproteins [very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL)] were isolated from stroke patients and healthy persons by ultracentrifugation. Lipoproteins were dialyzed into copper dichloride solution to study the effects of soycreme administration on lipoprotein peroxidation. Blood was drawn from 15 patients with cerebral thrombosis who were not administered soycreme, 10 patients with cerebral thrombosis who were administered soycreme and 11 healthy persons. The lipoproteins were dialyzed into 5 mol/l copper dichloride solution for various lengths of time, and then lipid constituents in the lipoproteins were measured by thin-layer chromatography. After the dialysis, percentages of cholesteryl ester and triglyceride in various lipoproteins decreased significantly (P < 0.05 or 0.01) in both patient groups and in healthy persons. Spot X1 was found between triglyceride and free fatty acid on the thin-layer chromatography, and spot X2 was located between free fatty acid and free cholesterol after dialysis. Spots X1 and X2 reflect lipoprotein peroxidation. Percentages of these spots were higher in VLDL, LDL and HDL in the patient groups than in the healthy subjects. Soycreme administration suppressed the appearance of spots X1 and X2. Furthermore, blood cholesterol concentrations were reduced by the administration of soy protein. Thus, soy may be useful in the prevention and/or treatment of atherosclerosis. PMID- 7884547 TI - New directions in dietary studies of coronary heart disease. AB - For several decades the debate on diet and coronary heart disease has been dominated by the classic diet-heart hypothesis, which predicts an adverse effect of dietary saturated fat and cholesterol and a beneficial effect of polyunsaturated fat intake. However, recent research suggests that the diet-heart relationship is much more complex than previously recognized. Antioxidants, and in particular vitamin E, are emerging as potentially useful protective factors, and there is increasing evidence that hyperhomocysteinemia is a risk factor that may be modified by dietary changes. However, substantial data support the notion that the trans fatty acids contained in partially hydrogenated vegetable oils adversely affect the risk of coronary heart disease. Other questions, such as the role of selenium and iron, the ideal amount in the diet of polyunsaturated fat of the n-6 or n-3 group (including fish oil) and how the benefits of a diet high in monounsaturated fat (such as the Mediterranean diet) compare with those of diet low in total fat (such as the traditional Asian diet) remain to be settled. PMID- 7884548 TI - Overview: dietary approaches for reducing cardiovascular disease risks. AB - Current interest in reducing heart disease risks by diet involves attention to total fat; saturated, monounsaturated, polyunsaturated and trans fatty acids, as well as dietary cholesterol, soluble fiber, salt, alcohol, antioxidants, dietary alterations causing homocysteinemia and other dietary constituents, such as flavonoid compounds in some soy products. Principles to consider in crafting dietary approaches to reducing heart disease risk and some future directions for research are summarized. Public information about dietary approaches for reducing heart disease risk will benefit from the Nutrition Labeling and Education. PMID- 7884549 TI - Incorporating soy proteins into baked products for use in clinical studies. AB - Recent research at the University of Illinois and elsewhere has shown that soy protein isolates and associated isoflavones are dietary constituents that are effective in decreasing risk of cardiovascular disease and cancer. If acceptable soy-based foods can be developed, the use of these products in typical diets can be increased. Many studies of the effects of soy protein in humans relied on addition or substitution of marginally palatable soy products in animal protein based diets. Subjects found it difficult to comply with long-term protocols using soy ingredients that had distinctive flavors and textures. Early attempts to develop palatable products with soy supplementation met with limited success. New processing methods have created a generation of soy protein isolates with mild flavors and aromas, as well as improved functionality, which can be incorporated into a variety of food products at levels high enough to have an effect on health. We have developed product and recipe formulations that can be satisfactorily incorporated into typical diets. The procedures used for product development, sensory evaluation of the products and the effect they can have on overall dietary intakes are discussed. PMID- 7884550 TI - Perspectives on soy protein as a nonpharmacological approach for lowering cholesterol. AB - Dietary therapy is the first step in the treatment of hyperlipidemia. However, some patients are unable to lower their cholesterol concentrations to a desirable range with diet alone. For primary prevention of coronary artery disease, physicians and patients often wish to avoid pharmacologic therapy of elevated cholesterol concentrations. The use of adjuncts to diet such as soluble fibers, garlic and soy protein may allow target lipid concentrations to be reached without the use of drugs. Soy protein incorporated into a low-fat diet can reduce cholesterol and LDL-cholesterol concentrations. The main obstacles to greater use of soy protein in the therapy of hyperlipidemia include lack of knowledge by physicians and patients of its effects and lack of availability of easily used products. Although soy products such as tofu and soymilk are available in many stores, consumers may be unaware of their presence and uses. Without the publication of articles in mainstream medical journals on the cholesterol lowering effects of soy protein, few physicians are likely to know of possible uses. Readily available packaged products, recipes and cookbooks also will be necessary to make incorporation of soy protein into the American diet a reality. PMID- 7884551 TI - Diet and heart disease: health claims. AB - The Nutrition Labeling and Education Act of 1990 states, in part, that a product is misbranded if it bears a claim that characterizes the relationship of a nutrient to a disease or health-related condition (health claim), unless the claim is made in accordance with Food and Drug Administration (FDA) regulations. In response to the new law, on January 6, 1993, the FDA promulgated regulations that described general requirements for health claims on foods in conventional food forms and specific requirements for seven authorized health claim topics. Three authorized claims are related to heart disease: dietary saturated fat and cholesterol and coronary heart disease; fruits, vegetables and grain products that contain fiber, particularly soluble fiber, and risk of coronary heart disease and sodium and hypertension. The general requirements regulation specifies the scientific standard for assessing the validity of claims, criteria for the qualification of claims, conditions for disqualification and general labeling requirements for health claims. Approval for health claims is based on the totality of publicly available scientific evidence and significant agreement among experts qualified by scientific training and experience to evaluate the relationship. On January 4, 1994, the FDA finalized similar requirements for health claims on dietary supplements. PMID- 7884552 TI - Diet, signal transduction and carcinogenesis. AB - The defects in the regulation of cell growth and differentiation that manifest themselves as cancer result from multiple defective genes and their products, which are involved in the processes of cellular signaling, regulation of gene expression and control of the cell through its replication cycle. Each of these molecular defects represents a new target for development of novel therapeutic agents and prophylactic interventions. Evidence suggests that such therapeutic agents will show great efficacy for cells made cancerous by the single targeted defect. However, poor anticancer efficacy for clinically presenting cancer may occur as a result of the multiple molecular lesions. A combined-agent approach seems likely to be more successful, but this will require diagnosis of each tumor in substantially greater detail, down to the molecular level. When such molecular diagnosis becomes generally feasible, it should be possible to use combinations of highly specific agents at very low doses for therapy and ultimately for prevention of tumor metastasis. Chemoprevention in general may be achieved more easily than therapy with mechanism-based interventions, as certain individual lesions, in theory, may be rate limiting for carcinogenesis but may not be a significant contributor to the neoplastic phenotype by the time the tumor presents in the clinic. PMID- 7884553 TI - An overview of clinical cancer chemoprevention studies with emphasis on positive phase III studies. AB - Cancer prevention aims to halt or reverse the development and progression of precancerous cells through the use of noncytotoxic nutrients and/or pharmacologic agents during the lengthy time period between tumor initiation and frank malignancy. This paper reviews cancer chemoprevention studies and focuses on Phase III trials, which are large, randomized, placebo-controlled studies that usually last several years. Studies may include multiple agents and dose levels, long-term toxicity evaluations or the modulation of surrogate endpoint biomarkers. Sample sizes of individual studies vary depending on statistical concerns and the demographics of the subject population. Recent Phase III trials include several promising agents: retinol; the retinoids 13-cis retinoic acid, all-trans-retinoic acid and 4-hydroxyphenyl retinamide; beta-carotene; finasteride and tamoxifen. Because one of the many actions of retinoids is the induction of epidermal differentiation, clinical trials with this class of agents have largely been conducted in epithelial or squamous cell tumor types. Several Phase III studies that have targeted the reversal of premalignant lesions or the prevention of second primary tumors have shown promising positive results. In contrast, some studies have shown that chemopreventive agents may have limited activity against the recurrence or progression of cells that have already undergone malignant transformation. Thus, the role of chemoprevention appears to lie in reversal of the premalignant process rather than suppression of malignant growth. PMID- 7884554 TI - Soy and experimental cancer: animal studies. AB - Studies are reviewed that report consumption of soy protein diets inhibits the growth of various tumors in rats. The inhibitory effect has been attributed to the phytoestrogens (genistein and diadzein) or protein kinase inhibitor in soy protein products. Recent studies indicate that additional factors in soy protein products may also contribute to the inhibition of tumorigenesis, namely the deficiency of the essential amino acid methionine. Metastatic growth to the lungs of a primary rhabdomyosarcoma tumor was inhibited by feeding a soy protein diet. The effect was reversed by methionine fortification of the diet. Carcinogen induced mammary tumor development was inhibited during the promotional phase in rats fed soy protein isolate diet and reversed with a methionine-supplemented diet. Additional studies demonstrated that after excision of the primary mammary tumor, growth of additional tumors was inhibited when the diet was changed from casein to soy protein isolate. Histopathologic evaluation of the mammary tumors revealed more benign fibroadenomas and lower-grade adenocarcinomas in the soy protein group. Before carcinogen administration (at 7 weeks of age), ornithine decarboxylase activity and polyamine concentrations in the rat mammary epithelium were significantly lower in the soy protein group. These data suggest an inhibitory effect on mammary epithelial growth in the soy-protein-fed group. PMID- 7884555 TI - Epidemiology of soy and cancer: perspectives and directions. AB - Previous epidemiologic studies of the effects of soy protein on cancer risk have been limited by small variations in soy intake, inability to separate soy from other dietary variables and difficulties inherent in relating dietary intake to the development of cancer several decades later. As a result, although existing data suggest that soy protein may be protective for cancer risk, results are overall inconclusive. There is also evidence that soy products may affect risk factors for cancer, such as endogenous hormone levels. Preliminary data from our group indicate that young Adventist women who are vegetarians with high soy intake and a lower risk of breast cancer may have higher levels of an adrenal androgen, dehydroepiandrosterone sulfate. Other groups have noted that soy protein may be associated with alterations in the regulation and binding of ovarian hormones. Additional studies examining effects of soy protein on risk factors for cancer would help, not only in delineating mechanisms of cancer development, but also in designing dietary programs aimed at cancer prevention. PMID- 7884556 TI - Cancer chemoprevention agent development strategies for genistein. AB - Cancer chemoprevention refers to the reduction of cancer incidence by administration of agents or drugs that inhibit, reverse or retard the cancer process. Genistein has demonstrated a wide variety of biological activities that make it a good candidate for a chemopreventive agent. Many agents, such as genistein, are currently being tested with the goal of developing safe and effective chemopreventive drugs for human use. Genistein was investigated as a potential chemopreventive agent in an azoxymethane-induced colon carcinogenesis model. Genistein was tested for its ability to inhibit aberrant colon crypts in the colon of F344 rats that had been treated with azoxymethane. Genistein was administered in the diet from 1 wk before the carcinogen to 4 wk after the first carcinogen dose for a total of 5 wk. At both doses, 75 and 150 mg/kg, the mean number of foci per colon was significantly reduced. Further development of this agent includes demonstration of the preventive efficacy in an in vivo tumorigenesis model, followed by preclinical pharmacology and toxicology testing. Phase 1, 2 and 3 clinical chemoprevention trials would be then performed to determine pharmacokinetics, safe doses, and effectiveness for New Drug Approval. PMID- 7884557 TI - Saponins as anticarcinogens. AB - Saponins, which are present in plants, have been suggested as possible anticarcinogens. They possess surface-active characteristics that are due to the amphiphilic nature of their chemical structure. The proposed mechanisms of anticarcinogenic properties of saponins include direct cytotoxicity, immune modulatory effects, bile acid binding and normalization of carcinogen-induced cell proliferation. However, the anticarcinogenic effects of saponins from commonly consumed plant foods have not been studied. Soybeans are one of the most important sources of dietary saponins. They are the main protein supplier in many vegetarian diets. Our results showed that soybean saponins at the concentration of 150-600 ppm had a dose-dependent growth inhibitory effect on human carcinoma cells (HCT-15). Viability was also significantly reduced. Soybean saponins did not increase cell membrane permeability in a dose-dependent fashion, whereas gypsophilla saponin, a nondietary saponin, increased permeability with increasing concentrations. Electron microscopy indicated that soybean and gysophilla saponins alter cell morphology and interact with the cell membrane in different ways. PMID- 7884558 TI - Inositol phosphates have novel anticancer function. AB - Inositol hexaphosphate (InsP6, phytic acid) is ubiquitous in the plant kingdom and is abundant in cereals and legumes. In much smaller amounts InsP6 and its lower phosphorylated forms (InsP1-5) are contained in most mammalian cells, where they are important in regulating vital cellular functions. Both in vivo and in vitro experiments have suggested striking anticancer potential (preventive as well as therapeutic) for InsP6 with and without inositol. In addition to reduce cell proliferation, InsP6 increases differentiation of malignant cells often resulting in reversion to the normal phenotype. InsP6 is quickly absorbed from the rat stomach and upper intestine and distributed as inositol and InsP1. In vitro it is instantaneously taken up by malignant cells undergoing variable dephosphorylation to inositol and InsP1-5, pointing toward their role in mediating the action of InsP6. Because InsP6 is high in high-fiber diets, our studies also may explain, at least in part, the epidemiologic observation showing high-fiber diets are associated with a lower incidence of certain cancers. Although further studies are needed to elucidate the mechanism(s) of this action, inclusion of InsP6 in our strategies for cancer prevention and therapy is warranted. PMID- 7884559 TI - The evidence for soybean products as cancer preventive agents. AB - There is much evidence suggesting that compounds present in soybeans can prevent cancer in many different organ systems. The evidence for specific soybean-derived compounds having a suppressive effect on carcinogenesis in animal model systems is limited, however. There is evidence that the following isolated soybean derived products suppress carcinogenesis in vivo: a protease inhibitor, the Bowman-Birk inhibitor, inositol hexaphosphate (phytic acid) and the sterol beta sitosterol. Other compounds that may be able to suppress carcinogenesis in animals are the soybean isoflavones. Soybean compounds reported to have other types of anticarcinogenic activity include soybean trypsin inhibitor, saponins and genistein. There is much evidence to suggest that diets containing large amounts of soybean products are associated with overall low cancer mortality rates, particularly for cancers of the colon, breast and prostate. It is believed that supplementation of human diets with certain soybean products shown to suppress carcinogenesis in animals could markedly reduce human cancer mortality rates. PMID- 7884560 TI - Possible adverse effects of soybean anticarcinogens. AB - For soybeans to serve as a good source of protein for feeding animals as well as humans, a certain amount of heat treatment or some other form of processing must be applied. This is because there are present in soybeans certain heat-labile factors that exert an adverse effect on the nutritional value of the protein. The so-called protease inhibitors have received the most attention in this regard and have been shown to exert their antinutritional effect in the short term by causing pancreatic hypertrophy and hyperplasia in the rat, the underlying cause for an inhibition of growth in these animals. The prolonged feeding of raw soy flour or an enriched trypsin inhibitor fraction from soybeans to rats results in the development of hyperplastic and neoplastic nodules of the pancreas, including carcinomas. It should be emphasized that all of these adverse effects are seen when protease inhibitors are present in relatively high concentrations in the diet and may be completely unrelated to the anticarcinogenic effects seen at low concentrations of the Bowman-Birk inhibitor. Brief mention is also made of any possible adverse effects that may result from the presence of phytic acid and saponins in soybeans. PMID- 7884561 TI - In vitro hormonal effects of soybean isoflavones. AB - Isoflavones exhibit a multitude of biological effects that influence cell growth and regulation, and, thus, may have potential value in the prevention and treatment of cancer. Isoflavones are weak estrogens and can function both as estrogen agonists and antagonists depending on the hormonal milieu and the target tissue and species under investigation. Genistein, one of the two primary isoflavones in soybeans, has attracted much attention from the research community, not only because of its potential antiestrogenic effects, but because it inhibits several key enzymes thought to be involved in carcinogenesis. Although still speculative, greater dietary incorporation of soybean products, because of the high concentration of isoflavones, may be a safe and effective means of reducing cancer risk. PMID- 7884562 TI - Soybean phytoestrogen intake and cancer risk. AB - Because many Western diseases are hormone-dependent cancers, we have postulated that the Western diet, compared with a vegetarian or semi-vegetarian diet, may alter hormone production, metabolism or action at the cellular level. Recently, our interest has been focused on the cancer-protective role of some hormone-like diphenolic phytoestrogens of dietary origin, the lignans and isoflavonoids. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids but also lignans), as well as whole grain cereals, seeds, probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds with weak estrogenic and antioxidative activity; they have now been shown to influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation and angiogenesis, making them strong candidates for a role as natural cancer protective compounds. Epidemiological investigations support this hypothesis, because the highest levels of these compounds are found in countries or regions with low cancer incidence. This report is a review of results that suggest that the diphenolic isoflavonoids and lignans are natural cancer protective compounds. PMID- 7884563 TI - Potential adverse effects of phytoestrogens. AB - Evaluation of the potential benefits and risks offered by naturally occurring plant estrogens requires investigation of their potency and sites of action when consumed at natural dietary concentrations. Our investigations have examined the effects of a range of natural dietary concentrations of the most potent plant isoflavonoid, coumestrol, using a rat model and a variety of estrogen-dependent tissues and endpoints. Treatments of immature females demonstrated agonistic action in the reproductive tract, brain, and pituitary at natural dietary concentrations. Experiments designed to test for estrogen antagonism demonstrated that coumestrol did not conform to the picture of a classic antiestrogen. However, coumestrol did suppress estrous cycles in adult females. Developmental actions were examined by neonatal exposure of pups through milk of rat dams fed a coumestrol, control, or commercial soy-based diet during the critical period of the first 10 postnatal days or throughout the 21 days of lactation. The 10-day treatment did not significantly alter adult estrous cyclicity, but the 21-day treatment produced in a persistent estrus state in coumestrol-treated females by 132 days of age. In contrast, the 10-day coumestrol treatments produced significant deficits in the sexual behavior of male offspring. These findings illustrate the broad range of actions of these natural estrogens and the variability in potency across endpoints. This variability argues for the importance of fully characterizing each phytoestrogen in terms of its sites of action, balance of agonistic and antagonistic properties, natural potency, and short-term and long-term effects. PMID- 7884564 TI - Effect of genistein on in vitro and in vivo models of cancer. AB - In two-thirds of studies on the effect of genistein-containing soy materials in animal models of cancer, the risk of cancer (incidence, latency or tumor number) was significantly reduced. In addition, purified genistein delayed mammary tumor appearance in association with increased cell differentiation in mammary tissue in rats treated with 7, 12-dimethylbenz[a]anthracene when administered neonatally, inhibited phorbol ester-induced H2O2 production in a model of skin cancer, and inhibited aberrant crypt formation in a model of colonic cancer. In in vitro models, genistein inhibited the proliferation of human tumor cell lines in culture with a wide variation in IC50 values (2.6-79 mumol/L, or 1-30 micrograms/mL). In only a few cases was the IC50 below 13.2 mumol/L (5 micrograms/mL), the presumed upper limit for the serum genistein concentration in those on a high soy diet. In future studies, greater emphasis should be placed on the effect of genistein on nontransformed, normal cell lines from the tissues where cancer can occur rather than established tumor cell lines. Similarly, the effect of genistein on the progression and/or promotion of cancer may be more clearly examined using nontransformed cell lines transfected with specific oncogenes thought to be activated during oncogenesis. PMID- 7884565 TI - Evaluation of the biochemical targets of genistein in tumor cells. AB - Although data from epidemiological studies and cancer models suggest that genistein plays an important role in cancer prevention, the biochemical target(s) of genistein action is (are) not known. Genistein is a potent in vitro inhibitor of protein tyrosine kinase (PTK) activity, especially that of the epidermal growth factor receptor (EGF-R), having little effect on serine/threonine kinases. This led to the suggestion that genistein might exert its anti-cancer effects through inhibiting the activity of EGF-R PTK, or other crucial PTK's in vivo. Subsequent studies on intact tumor cell lines demonstrated that EGF-R and other growth factor receptors are able to transmit mitogenic signals in the presence of genistein. In fact, it is difficult to detect decreases in the tyrosine phosphorylation of discrete proteins after genistein treatment. Other mechanisms for the effect of genistein have been suggested from in vitro and cell culture data. Genistein not only inhibits the activity of purified topoisomerase II in vitro, but also leads to the accumulation of protein-associated single strand breaks in whole cells. Genistein also inhibits the production of reactive oxygen species which may lead to tissue damage and DNA modification. Additionally, genistein acts as a weak estrogen, modifies cellular differentiation programs, inhibits angiogenesis. modulates cell cycle events and may precipitate apoptosis. However, few of the above mechanisms in tumor cells are sensitive to the physiological serum concentrations of genistein (< 18.5 mumol/L, or < 5 micrograms/mL). Primary, nontransformed human mammary epithelial cells, which have a much greater sensitivity to genistein, would be a better system for the study of these mechanisms. PMID- 7884566 TI - Re: B-scan ultrasonic measurement of the lumbar spine canal as a predictor of industrial low back pain complaints and extended work loss, by M Battie et al. PMID- 7884567 TI - Re: Successful treatment of life-threatening proprionitrile exposure with sodium nitrite/sodium thiosulfate followed by hyperbaric oxygen, by Scolnick et al. PMID- 7884568 TI - Elevated dioxin blood levels in British chemical workers. PMID- 7884569 TI - Surgical gloves and hypersensitivity to latex. PMID- 7884570 TI - Sleep and alertness in a 12-hour rotating shift work environment. AB - Industrial workers on rotating shifts were evaluated for the effects of rotating shift work. Twenty-five (86%) of 29 workers in the study area who work 12-hour shifts in a scheduled 16-day rotation participated. The mean number of hours of sleep at home after working day shifts (5.6 hours) was less than after the first three night shifts (6.0, 6.4, and 6.6 hours, respectively). At work, the mean number of hours at reported peak alertness was greater during the night shift (6.1 hours) than the day shift (4.9 hours), but the perceived alertness levels were relatively lower on the night shift. Increased perceived difficulty working and decreased perceived productivity and safety were reported on the first night of the night shift. We demonstrate that workers on rotating shift work exhibit low alertness-related outcomes on both shifts. These workers have early shift work starting times that appear to disrupt sleep patterns on both day and night shifts. At this work site, a number of interventions to lessen the effects of rotating shift work are being evaluated. PMID- 7884571 TI - Mortality of iron foundry workers. III. Lung cancer case-control study. AB - A nested case-control study was undertaken to identify the determinants of lung cancer mortality in a cohort of 8147 foundry men among whom an excess of lung cancer deaths was previously observed. The present study consisted of all lung cancer deaths (N = 220) that occurred within this cohort between 1950 and 1989. both living and dead controls, matched on race and attained age, were selected in the ratio of 10:1 (N = 2200) by means of the incidence density sampling procedure. All cases and two controls per case, randomly selected from each case's 10 controls, were included in a smoking history survey. Basic smoking history information was obtained for about 71% of these study subjects. For the purpose of this study, formaldehyde exposure levels were categorized as high, medium, low, and none. Airborne silica exposure was categorized only as high, medium, and low levels, because all foundry workers were known to be exposed to silica. Conditional logistic regression analyses indicated that cigarette smoking was a strong predictor of lung cancer mortality in this cohort. Neither exposure to formaldehyde nor silica exposure level, nor employment in any of the six major work areas within the foundry, showed an association with lung cancer. PMID- 7884572 TI - Hazardous waste worker education. Long-term effects. AB - This study illustrates how a union education center successfully integrated adult empowerment education principles into the teaching methods and curriculum of a health and safety training program. The 12-month follow-up phone survey involved 481 local union respondents each representing a separate plant site and a group of 50 manager trainees. The evaluation shows that the training manual continued to be used by more than 70% of respondents, more than 70% taught coworkers, more than 50% of union trainees went on to train their managers, and more than 90% identified problems at work and sought and obtained changes in programs, training, or equipment. More than 20% reported that major spills had occurred following training. The majority stated that the handling of the spills improved. More than 80% stated that the training better prepared them for their health and safety duties. The managers' data substantially supported union members' reports. PMID- 7884573 TI - The detection of increased amounts of the extracellular domain of the epidermal growth factor receptor in serum during carcinogenesis in asbestosis patients. AB - Overexpression of the epidermal growth factor receptor (EGFr) has been implicated in the pathogenesis of a wide variety of human malignancies and may be related to asbestos-induced carcinogenesis. Overexpression of the EGFr can be detected immunologically by quantitation of the extracellular domain (ECD) in the extracellular fluid in vitro and in serum in vivo. An enzyme-linked immunosorbent assay (ELISA) for the EGFr ECD was used to examine banked serum samples of 38 asbestosis patients who subsequently developed cancer, 72 age-sex-race-smoking asbestos exposure matched asbestosis controls without cancer, and 20 age-sex-race smoking matched nonasbestosis noncancer controls. The mean serum level for the EGFr ECD in the cancer cases (636 +/- 299 fmol/ml) was statistically significantly elevated (P < 0.05) in comparison to the mean level in the asbestosis controls (546 +/- 147 fmol/ml) or the nonasbestosis controls (336 +/- 228 fmol/ml). Defining a positive elevation of the serum EGFr ECD as any value more than 2 standard deviations above the nonasbestosis control mean, 7 (18%) of the cancer cases were positive compared to 4 (6%) of the asbestosis controls and one (5%) of the nonasbestosis controls. In addition, all of these cancer cases had positive serum samples prior to the time of disease diagnosis (average = 5.1 years). These results suggest that serum EGFr ECD may be elevated at an early stage of carcinogenesis in some asbestosis patients and that further prospective study of the utility of this biomarker is warranted. PMID- 7884574 TI - Exposure to biogenic silica fibers and respiratory health in Hawaii sugarcane workers. AB - We conducted a cross-sectional environmental and medical survey of 355 male sugarcane workers in Hawaii to determine whether exposure to biogenic silica fibers (BSF) affected their respiratory health. Exposures to BSF ranged from nondetectable to more than 0.700 BSF/mL and varied by job and department. Respiratory symptoms, chest radiograph findings, and pulmonary function were not associated with BSF exposures. Cigarette smoking was associated with respiratory symptoms and pulmonary obstruction. Fifteen workers had pleural thickening or pleural plaques and 3 of these workers were exposed to BSF for more than 10 years. BSF exposure does not appear to influence the respiratory health of sugarcane workers; however, further study is warranted. PMID- 7884575 TI - Teaching stress management skills to occupational and environmental health physicians and practitioners. A graduate-level practicum. AB - The World Health Organization Study Group on Training and Evaluation in Occupational Medicine has emphasized recently the importance of incorporating theoretical and practical aspects of primary and secondary prevention of stress in the professional training of occupational health practitioners. This paper describes such a course developed for the Tel-Aviv University Medical School graduate program in occupational health. The course objectives are consistent with the current call for improved training in psychosocial issues in medical care. Twenty-three occupational health practitioners (physicians, nurses, hygienists, and social workers) participated in a bisemester course. The first part included a stress management and prevention program based on the Rational Emotive Training model. The main aim was to reduce irrational or dysfunctional thinking, which is considered a causal factor in stress and burnout. The second part involved the development and implementation of a field project on primary and secondary prevention of stress and its outcomes. Precourse, midcourse, and postcourse questionnaires showed a significant improvement in participants' psychosocial ability and a reduction in dysfunctional thinking compared with the control group. Such antistress resources may benefit practitioners and clients or patients alike, both potential victims of occupational stress. PMID- 7884576 TI - High-cost analysis. A closer look at the case for work-site health promotion. AB - Studies linking medical costs to behavioral risk and risk-lowering often use means for comparisons, although claims data are highly skewed. The result overestimates and obscures the case for work-site health promotion. In this study, high-cost analysis is illustrated in a sample of university employees. Five risk factors were examined: cholesterol, blood pressure, cardiovascular fitness, body fat, and smoking status. Screened employees who released their claims (n = 367) were examined against a random sample of employees (n = 587). Linear regression was used to determine the risk of having high claims costs within four gender-specific age groups. A formula was then applied to determine that more than 43% of the cost of medical claims was associated with elevated risk. High-cost analysis accounts for the skewness in claims data and presents a clear case for work-site health promotion. PMID- 7884577 TI - The private funding of public research. New directions in the administration of occupational and environmental health research. AB - Dr. Cullen: The experience with the new research models, starting with the prototypic experience of the rubber industry studies of the 1970s and expanding to diverse sectors of American industry in the 1980s, has yielded some important lessons for the future. In closing this symposium I shall try to summarize these briefly. Certain strengths of the evolving process seem common to each of the models. Alone and collectively, the new research arrangements have quite apparently served to increase substantially the pool of funds available to the academic sector for the study of occupational health and safety problems. As a consequence, a larger pool of investigators has participated in the research process, greatly strengthening the future academic capability and experience of our fragilely supported teaching centers. Combined with the involvement of the academic centers in the review process, there has been an undeniable broadening and deepening of the nation's research output and long-term capability in occupational health. On the side of the private sector, the new relationships have led to marked progress in the knowledge base about health and safety problems, with a heavily directed focus on those of greatest relevance to the industries involved. The credibility of the knowledge acquired has been enhanced, an important achievement in a society in which perception of truth is often as important as the truth itself! Because of the requirements of the process for broad involvement by the organizations which undertake these activities, health and safety have achieved far greater visibility and attention by corporate and union leaders who may have previously had no involvement in issues of health and safety.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884578 TI - TCV 116 prevents progressive renal injury in rats with extensive renal mass ablation. AB - OBJECTIVE: The objective of this study was to determine the renal protective effects of TCV 116, a novel, non-competitive, angiotensin II type 1 (AT1) receptor antagonist, in rats with 5/6 renal mass ablation. DESIGN: Adult male Wistar rats were subjected to 5/6 nephrectomy and treated continuously with either TCV 116 (group I, n = 8; group III, n = 9) or vehicle (group II, n = 8; group IV, n = 8). The development of elevated systolic blood pressure, 24-h urinary protein excretion, glomerular hemodynamics and glomerular morphology were compared among groups. RESULTS: Systolic blood pressure rapidly reached hypertensive levels in group II, increasing from 175 +/- 8 mmHg after 3 weeks to 221 +/- 15 mmHg after 12 weeks, whereas group I rats remained normotensive (101 +/- 8 to 112 +/- 6 mmHg). Similarly, urinary protein excretion increased from 45 +/- 11 to 104 +/- 18 mg/day in group II, but remained low (6.9 +/- 1 to 19 +/- 4 mg/day) in group I. After 12 weeks, there was an average of 42 +/- 6% glomerulosclerosis in group II, but only 1.6 +/- 0.5% in group I. After 4-6 weeks, a markedly elevated glomerular capillary pressure (62 +/- 1.2 mmHg) was observed in group IV, but the pressure was normal in group III (50 +/- 1.1 mmHg). CONCLUSIONS: These data show that TCV 116 prevents the development of systemic hypertension, glomerular capillary hypertension, proteinuria and glomerulosclerosis in rats with reduced renal mass. We therefore conclude that the renal protection associated with angiotensin I converting enzyme inhibitors and other pharmacologic blockers of the renin-angiotensin system arises chiefly from blockade of AT1 receptor-mediated hemodynamic effects. PMID- 7884579 TI - Widespread tissue distribution of human chymase. AB - OBJECTIVE: Human chymase is a potent and specific angiotensin (Ang) II-forming serine proteinase. Although the histological localization of heart chymase indicated that this enzyme contributes to extracellular Ang II formation, the systemic distribution and the level of expression of chymase in various human tissues have not been clarified. This information is needed to elucidate the human tissue Ang II system. METHODS: Levels of immunoreactivity and enzymatic activity in various human tissues were evaluated respectively by Western blot analysis and by an enzymatic assay for Ang II-forming activity from Ang I. RESULTS: High levels of chymase-like immunoreactivity were found in alimentary tract tissue, uterus and tonsil; moderate levels were found in both cardiac ventricles, lung, adenoid and liver; low levels were found in the cardiac atria, coronary artery, aorta and skin; and almost undetectable levels were found in the spleen and kidney. High levels of chymase-like enzymatic activity were detected in skin, oesophagus, stomach and uterus; moderate levels were found in both cardiac ventricles, lung, colon, tonsil, adenoid and renal cortex; and low levels were found in the cardiac atria, coronary artery, aorta, spleen, renal medulla and liver. CONCLUSIONS: Our studies have revealed heterogeneous and widespread tissue distribution of human chymase throughout the human body and indicate that chymase probably has a significant influence not only in the heart but also in other tissues. PMID- 7884580 TI - Involvement of the renin-angiotensin system in the development of left ventricular hypertrophy and dysfunction. AB - OBJECTIVES: To elucidate the regulation of cardiac gene expression by mechanical stress and to analyse molecular mechanisms associated with the involvement of angiotensin II (Ang II) in the development of cardiac hypertrophy and dysfunction. METHODS: Neonatal rat cardiocytes were cultured in deformable silicone dishes, and mechanical stress was imposed on the cardiocytes by stretching them. In in vivo studies, spontaneously hypertensive rats (SHR) were treated with a non-peptide, specific Ang II type 1 receptor antagonist, TCV 116. RESULTS: Expression of the c-fos gene was rapidly induced, and fetal type genes such as skeletal alpha actin and beta myosin heavy chain genes were re-expressed by stretching. The mechanical stress decreased the expression of Ca(2+)-ATPase in the sarcoplasmic reticulum. With regard to signals for the development of cardiac hypertrophy, mechanical stress evoked c-fos expression via the activation of protein kinase C. The phosphorylation cascade (sequential activation of protein kinase C, Raf-1 kinase, mitogen-activated protein kinase kinase, mitogen activated protein kinase and S6 kinase), which may be involved in protein synthesis and gene expression, was activated by mechanical stress in cardiocytes. Stretch-induced cardiac cellular hypertrophy was partially inhibited by TCV 116. TCV 116 treatment of SHR reduced left ventricular weight, left ventricular wall thickness, myocyte transverse diameter, V3 myosin heavy chain levels and the interstitial collagen volume fraction. CONCLUSIONS: These results indicate that AngII may, in part, mediate the stretch-induced hypertrophic growth of cardiomyocytes via the type 1 Ang II receptor. PMID- 7884581 TI - Angiotensin II antagonists DuP 753 and TCV 116. AB - BACKGROUND: Acute blockade of the renin-angiotensin system with the parenterally active angiotensin II antagonist saralasin has been shown to effectively lower blood pressure in a large fraction of patients with essential hypertension and to improve haemodynamics in some patients with congestive heart failure. It is now possible to chronically antagonize angiotensin II at its receptor using non peptide angiotensin II inhibitors such as losartan (DuP 753/MK-954) or TCV 116. EFFECT OF NON-PEPTIDE ANGIOTENSIN II ANTAGONISTS: When administered by mouth, DuP 753 and TCV 116 induce dose-dependent inhibition of the pressor response to exogenous angiotensin II. This effect is closely related to circulating levels of the corresponding active metabolites E3174 and CV11974. Preliminary studies performed in hypertensive patients suggest that losartan lowers blood pressure to an equivalent extent to an angiotensin converting enzyme (ACE) inhibitor. CONCLUSIONS: Further investigation is required to show whether these new angiotensin II antagonists compounds compare favourably with ACE inhibitors. PMID- 7884582 TI - Angiotensin II receptor antagonists versus angiotensin converting enzyme inhibitors: effects on renal function. AB - PURPOSE: Recent work has suggested that proximal tubular reabsorption of sodium may be regulated by a local renin-angiotensin system which may be independent of the circulating renin-angiotensin system. The aim of this review was to examine the long-term renal consequences of blockade of the renin-angiotensin system by angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists. RESULTS: Except in states of extreme volume depletion, in which ACE inhibitors may, unlike angiotensin II receptor antagonists, have an adverse effect on the glomerular filtration rate, no differences were observed between the two types of inhibitor. Like ACE inhibitors, the angiotensin II inhibitors TCV 116 and losartan cause a marked impairment in the renal adaptation to dietary sodium restriction, suggesting that blockade of the renin-angiotensin system is primarily involved in this process. CONCLUSIONS: Further studies in human renovascular hypertension and chronic renal disease are required. PMID- 7884583 TI - Open clinical studies on a new angiotensin II receptor antagonist, TCV 116. AB - OBJECTIVES: The goals of these preliminary studies were to evaluate the effects of a new angiotensin II receptor antagonist, TCV 116, on the daytime blood pressure profile in hospital inpatients with essential hypertension, and to evaluate the clinical efficacy and safety of this agent in outpatients with essential hypertension. SUBJECTS: In study 1, daytime blood pressure changes were studied in 28 inpatients with mild to moderate essential hypertension (systolic blood pressure > or = 150 mmHg, diastolic blood pressure > or = 90 mmHg). In study 2, 55 outpatients with essential hypertension (systolic blood pressure > or = 160 mmHg, diastolic blood pressure > or = 95 mmHg) were enrolled in a dose finding study. METHODS: In study 1, after a 1-week placebo run-in period, blood pressure and the pulse rate were measured every 2 h except at night. TCV 116 monotherapy was started at 1 mg/day and increased stepwise at 3- to 5-day intervals to 2, 4 and 8 mg/day until a predetermined reduction in blood pressure was achieved. The daytime profiles of blood pressure and the pulse rate were again monitored at the end of the treatment period. In study 2, after a 4-week placebo run-in period, TCV 116 alone was administered for 2 weeks at 1 mg/day. The dose was then increased to 2 mg/day and stepwise at 2-week intervals to 4 and 8 mg/day until a predetermined reduction in blood pressure was achieved. The total treatment period was 8-12 weeks. RESULTS: In study 1, a sufficient reduction in blood pressure was achieved in 19 of 28 patients (68%), with blood pressure significantly reduced at all measurement points, compared with the placebo run-in period. No differences were seen in the pulse rate. The only adverse reaction reported was a rash in one patient. In study 2, a sufficient reduction in blood pressure was achieved in 42 out of 55 patients (76%). The cumulative efficacy rate increased dose-dependently (15% at 1 mg/day, 38% at 2 mg/day, 60% at 4 mg/day and 76% at 8 mg/day). No differences were seen in the pulse rate. Adverse reactions were reported in three out of 55 patients (5.5%). No dry cough was reported by any of the patients. CONCLUSIONS: TCV 116, an angiotensin II receptor antagonist, has potential as an antihypertensive agent. A dose of 4-8 mg once per day appears to be appropriate for the treatment of patients with mild to moderate essential hypertension. PMID- 7884584 TI - Recombination pattern of the TCR gamma locus in human peripheral T-cell lymphomas. AB - The recombination events of the gamma and beta T-cell receptor (TCR) loci were analysed in a series of 39 peripheral T-cell lymphomas (PTCLs) in association with the expression of TCR chains. In TCR alpha beta PTCLs, 22/23 cases showed a gamma-gene rearrangement while only 18/23 showed a concomitant beta-gene rearrangement. The germline configuration of the beta locus was found in angiommunoblastic lymphadenopathy and lymphoepithelioid lymphomas. Three gamma delta PTCLs rearranged both gamma and beta genes. TCR silent PTCLs showed three different patterns of gamma- and beta-gene rearrangements. Three cases were in germline configuration for both loci; five cases had a rearranged gamma and a germline beta locus; and five cases had the two loci rearranged. Regarding the variable genes in the gamma-rearranged alleles, members of the V gamma I subgroup were the most frequently presented (39/50), followed by V gamma II, V gamma III, and V gamma IV (9/50, 1/50, and 1/50, respectively). Joining segment usage was as follows: J1 or J2 (32/50), JP1 or JP2 (17/50), and JP (1/50). Taken together, these data demonstrate that the gamma locus is more frequently rearranged whatever the TCR expression. The gamma-locus analysis provides a better diagnostic yield than the beta locus in the study of PTCL clonality. PMID- 7884585 TI - Loss of membranous E-cadherin expression in pancreatic cancer: correlation with lymph node metastasis, high grade, and advanced stage. AB - Epithelial cadherin (E-cadherin) is a Ca(2+)-dependent cell-cell adhesion molecule that connects cells via homotypic interactions. Its function is critical in the induction and maintenance of cell polarity and differentiation, and its loss of downregulation is associated with an invasive and poorly differentiated phenotype in colon and other tumors. We have used an avidin-biotin immunoperoxidase technique to localize E-cadherin in microwave-treated, paraffin embedded sections from 36 patients with pancreatic adenocarcinomas. E-cadherin was expressed by normal ductal and acinar cells with typical membranous staining at the intercellular junctions. Loss of normal surface E-cadherin expression was found in 19/36 (53 per cent) tumours compared to the adjacent normal ductal cells. Abnormal E-cadherin expression was found more frequently in poorly differentiated (grade III) (6/7, 86 per cent) than in well-differentiated tumors (grade I) (4/14, 28 per cent) (P = 0.012). Membranous E-cadherin expression was also lost more frequently in primary tumours with lymph node (stage III) (14/23, 61 per cent) and distant metastasis (stage IV) (2/2, 100 per cent) compared with 3/11 (27 per cent) lymph node-negative tumours (stage I) (P = 0.043). In conclusions, our data indicate that loss of membranous E-cadherin expression is associated with high grade and advanced stage in pancreatic cancer. PMID- 7884586 TI - Atypical alveolar hyperplasia: relationship with pulmonary adenocarcinoma, p53, and c-erbB-2 expression. AB - Atypical alveolar hyperplasia (AAH) has recently been described in human lungs in association with primary lung cancer, particularly adenocarcinoma. Unlike proximal bronchogenic carcinoma, peripheral (parenchymal) adenocarcinoma of the lung does not have a well-recognized progenitor lesion. Epidemiological morphometric, and cytofluorometric data in the literature suggest that AAH is a candidate premalignant entity. In this study, 97 AAH lesions were found in lungs resected from 29 patients (1-13 lesions per case, mean 3.5) being treated for presumed carcinoma (25/29 had adenocarcinoma). From a study case-load of 285 adenocarcinoma-bearing lungs, the AAH incidence was 8.8 per cent. Sections of 67 AAH lesions from 19 patients were stained using monoclonal antibodies against Ki67 (MIB1), p53 (DO7), and c-erbB-2 (NCL-CB11). Ki67 was expressed in up to 10 per cent of AAH nuclei. Thirty-nine lesions (58 per cent) showed stainable p53 protein, while five (7 per cent) expressed membrane c-erbB-2 oncoprotein. These latter five lesions were all strongly positive for p53, and both p53 and c-erbB staining was associated with increased cellular crowding and pleomorphism in AAH. These data demonstrate that AAH exhibits some genetic changes associated with malignancy and thereby support the hypothesis that AAH is premalignant. PMID- 7884587 TI - Incidence of latent infection of Epstein-Barr virus in lung cancers--an analysis of EBER1 expression in lung cancers by in situ hybridization. AB - To evaluate the presence of Epstein-Barr virus (EBV) in lung cancers of Japanese patients, 81 lung cancers were examined using a highly sensitive in situ hybridization (ISH) method, employing an antisense oligonucleotide probe for EBV encoded small nuclear RNA-1 (EBER). EBER1 expression was demonstrated in one poorly differentiated squamous cell carcinoma associated with marked lymphoid stroma (PDSCC-LS), two well differentiated adenocarcinomas, and two moderately differentiated squamous cell carcinomas, but was not detectable in other lung cancers, including small cell carcinomas. Unlike lymphoepithelioma-like undifferentiated carcinoma (LELC) of the lung, the PDSCC-LS consisted of poorly differentiated cells with distinct cell borders and nuclei with a coarse chromatin pattern and some prominent nucleoli. Most of the cancer cells expressed intense EBER1 signals. Although small to moderate numbers of cells positive for EBER1 were present in two adenocarcinomas and two squamous cell carcinomas, EBER1 signals varied in intensity and number in these four cases. Although polymerase chain reaction (PCR) and Southern blot hybridization with a 32P-labelled probe internal to the primers were conducted to detect the EBV genome in 24 lung cancers, including five EBER1-positive cases, the genome was found to be positive in the five cases with EBER1-positive staining, including the PDSCC-LS, two adenocarcinomas and two squamous cell carcinomas, but not in the other cases. This study indicates that the morphological features of EBV-associated lung cancers are not restricted to the typical LELC type. PMID- 7884588 TI - p53 protein, PCNA staining, and DNA content in follicular neoplasms of the thyroid gland. AB - Forty-nine follicular adenomas and 11 follicular carcinomas of the thyroid were investigated by immunohistochemistry for the expression of p53 protein and proliferating cell nuclear antigen (PCNA). The DNA ploidy and the S-phase fraction (SPF) of the neoplasms were analysed by flow cytometry. Twelve adenomas (24 per cent) and six carcinomas (55 per cent) were DNA non-diploid (P = 0.07). The carcinomas had a higher proliferation rate than the adenomas when assessed either by SPF size (median 9.9 per cent vs. 2.9 per cent, P = 0.0003) or by PCNA staining intensity (P < 0.0001). Some scattered nuclei in two (4 per cent) adenomas and in three (27 per cent) carcinomas stained positively for p53 (P = 0.04). The two adenomas with positive staining for p53 were subserially sectioned, but no signs of invasion were found; both patients are alive and well 6 and 7 years after surgery. One of the two adenomas showing positive p53 nuclear staining was DNA aneuploid, and both were positive in PCNA staining, but their SPFs were low (2.1 and 3.3 per cent). We conclude that p53 protein expression is not confined to follicular carcinomas; scattered p53-positive cells may also be present in histologically and clinically benign follicular adenomas. Because both follicular adenomas and carcinomas may be DNA aneuploid and their SPF and PCNA staining distributions overlap, the distinction between follicular adenoma and carcinoma should still be based on histological criteria. PMID- 7884589 TI - Prognostication of astrocytoma patient survival by Ki-67 (MIB-1), PCNA, and S phase fraction using archival paraffin-embedded samples. AB - The prognostic power of three proliferation estimation methods, Ki-67 (MIB-1) and PCNA immunohistochemistry, and flow cytometry (S-phase and S + G2/M fractions, respectively), were evaluated in 50 cases of astrocytoma. Each proliferation index showed a strong association with the grade of malignancy (grades I-IV). The MIB-1 labelling index (LI) provided additional information, as it could be used for the discrimination of grade II and grade III astrocytomas (P = 0.0357). All three proliferation estimation methods also had strong prognostic potential (MIB 1 LI: P < 0.0001; PCNA Li: P < 0.0001; S-phase: P = 0.0004; S + G2/M: P = 0.0124). According to the receiver operating characteristics (ROC) curve, the MIB 1 LI showed generally the best sensitivity and specificity in placing the patients correctly into groups of survivors and non-survivors, which was further confirmed in the multivariate analysis. Only 4 per cent of the patients having high MIB-1 scores (> 15.3 per cent) were alive after 2-years' follow-up. In contrast, 72 per cent of patients with tumours of low proliferation activity survived. It appears that Ki-67 (MIB-1) immunolabelling using archival paraffin embedded samples is of value in predicting prognosis in astrocytic tumours. PMID- 7884591 TI - Characterization of a subtype of primary osteoclastoma: extracellular calcium but not calcitonin inhibits aggressive HLA-DR-positive osteoclastoma possessing 'functional' calcitonin receptors. AB - We report here a case of primary osteoclastoma that despite possessing HLA-DR positive status and 'functional' calcitonin receptors, exhibited aggressive in vitro and in vivo bone resorptive activity. In the osteoclast bone slice assay employing scanning electron microscopy, the giant cell-mediated bone resorption was uninhibited by salmon calcitonin (10 nM) and significantly inhibited by raised extracellular calcium (20 mM). In Fura-2AM based microspectrofluorimetric assays, the presence of the 'functional' calcitonin receptors was ascertained by a rise in intracellular calcium induced by calcitonin and high extracellular calcium. These findings provide evidence for a hitherto unrecognized subtype of giant cells that have HLA-DR-positive status, exhibit avid bone resorptive activity, but remain insensitive to calcitonin despite possessing calcitonin receptors. PMID- 7884590 TI - The expression pattern of contractile and intermediate filament proteins in developing skeletal muscle and rhabdomyosarcoma of childhood: diagnostic and prognostic utility. AB - In order to investigate whether rhabdomyosarcoma (RMS) can be related to equivalent stages of skeletal muscle development, muscle tissue of 21 human foetuses and 112 primary RMSs were characterized immunohistochemically using antibodies directed against vimentin, desmin, muscle-specific actin (HHF35), sarcomeric actin (sr-actin), smooth muscle actin (sm-actin), and troponin-T. During fetal skeletal muscle development, all myotubes/fibres of the first and second generations expressed desmin, HHF35, and sr-actin. Vimentin was almost exclusively present in immature primary and secondary myotubes/fibres. Troponin-T was expressed in immature myotubes/fibres of the first and second generations as well as mature fibres of the second generation. Sm-actin was never expressed. Vimentin was expressed in 96 per cent of primary and 98 per cent of relapsed RMS; HHF35 in 96 and 98 per cent, respectively; desmin in 95 and 100 per cent; troponin-T in 82 and 75 per cent; sr-actin in 71 and 86 per cent; and sm-actin in 13 and 17 per cent. The proportion of RMS cells reacting with vimentin, HHF35, and desmin was consistently higher than those expressing sr-actin and troponin-T. Neither the shape nor size of neoplastic RMS cells nor the histopathological types were related to the expression pattern of the investigated markers. RMS with aberrant expression of two or more markers predicted a worse prognosis than RMS in which at most one marker was aberrantly expressed (25 per cent and 54 per cent 10-year survival, P = 0.01). These results demonstrate that HHF35, desmin, sr-actin, and troponin-T have the potential to confirm the commitment of the tumours to the myogenic pathway which supports the diagnosis of RMS. However, it was impossible to relate RMS to equivalent stages of skeletal muscle development. Aberrant marker expression by RMS cells correlated significantly with patients' survival. PMID- 7884592 TI - Possible role of tissue-bound calcium ions in citrate-mediated high-temperature antigen retrieval. AB - High-temperature preheating of sections in the presence of a salt (e.g., citrate) or a protein denaturant (e.g., urea) solution has been shown recently to provide a reliable alternative to tissue proteolysis for antigen retrieval from formaldehyde-fixed, paraffin-embedded tissues. However, the underlying mechanism of action of this form of pretreatment remains highly speculative. In this study, we show that calcium chelating agents such EDTA and EGTA are more effective than citrate in the retrieval of a citrate-sensitive nuclear antigen, Ki-67. Also, sodium carbonate and another calcium precipitating agent are both able to effect antigen retrieval at high temperatures. The overall data therefore suggest that either the chelation or the precipitation of tissue-bound calcium ions, and perhaps also other divalent metal cations, is a critical step in salt-mediated antigen retrieval. As a corollary, it is suggested that tight complexing of calcium ions or other divalent metal cations with proteins during formaldehyde tissue fixation is responsible for the masking of certain antigens. PMID- 7884593 TI - In defence of the post-mortem demonstration. PMID- 7884594 TI - Traumatic experiences and substance abuse. PMID- 7884596 TI - Alcoholism and trauma: a theoretical overview and comparison. AB - This article outlines a theoretical overview of evolving conceptions of trauma and their application to alcoholism. Traditional definitions of trauma are reviewed and Judith Herman's theory of psychological trauma and the process of recovery are summarized. This framework is used to describe the experience of being alcoholic, the child of an alcoholic (COA), the adult child of an alcoholic parent (ACA), and of being both alcoholic and an ACA. The developmental process of recovery within the 12-Step framework is compared to Herman's stages of trauma resolution. It is argued that trauma theory must be expanded to adequately described and explain the experiences of alcoholism and that issues of power and control must be reinterpreted to fit within the 12-Step model. This article posits that trauma theory offers an important link between the professional worlds of chemical dependency treatment and mental health. PMID- 7884595 TI - Traumatic experiences and substance abuse: mapping the territory. AB - This article examines the relationships between various types of traumatic experiences and addictive behavior, with an eye to formulating effective treatment strategies. Interventions in the posttraumatic stress disorder (PTSD) and related fields are reviewed in an effort to understand how best to integrate them into substance abuse treatment. The recovery-oriented therapy model is used as a framework to define treatment tasks at each stage of the recovery process: how one addresses painful issues depends on the objective, given the recovery stage at hand. These tasks include making a commitment to abstinence, stopping alcohol and other drug use, consolidating abstinence and changing lifestyles, and addressing short- and long-term psychosocial issues. The article focuses on the clinical features of PTSD in an effort to enhance the practitioner's ability to address this disorder within the context of substance abuse treatment. Finally, recommendations are offered for training practitioners at varying skill levels in the addiction treatment field. PMID- 7884597 TI - Trauma symptoms in substance abusers with and without histories of childhood abuse. AB - This study was designed to provide a prevalence rate of childhood abuse in patients being treated for alcohol and other drug problems, and to compare the extent of trauma symptoms that were present in substance abusers with and without childhood histories of physical, sexual, and emotional abuse. One hundred male veterans completed a standard test battery that included the Trauma Symptom Checklist and the Dissociative Experiences Scale. Clinical information pertaining to history of childhood abuse was obtained from the subjects' medical charts. Results demonstrated that 34% of the sample reported a history of childhood abuse. Although this group did achieve higher mean scores on all the scales, in comparison to the nonabused group, statistical significance was absent. Implications of these findings are discussed and future research is suggested. PMID- 7884599 TI - Integrated treatment for the survivor of childhood trauma who is chemically dependent. AB - A substantial percentage of individuals who are chemically dependent also suffer from posttraumatic stress disorder and other survivor syndromes related to childhood abuse. The synergism of these multiple conditions creates unique treatment challenges. An enhanced, integrated treatment approach increases the chances of a successful clinical outcome. This article discusses a treatment model for chemical dependence and trauma-related syndromes that blends mental health and 12-Step and other chemical dependence treatment notions into an integrated approach that treats both disorders simultaneously and comprehensively. The model uses the strategic principle of "safety first" to drive all interventions and has five stages to organize the selection and timing of treatment tactics: crisis, skills, education, integration, and maintenance. This article also presents specific therapeutic tactics for each stage and a composit case example blending the history and recovery process of a survivor to illustrate the model in action. PMID- 7884598 TI - History of sexual assault and the treatment of substance abuse disorders. AB - A treatment outcome study of adult patients treated for substance abuse disorders was conducted in which 80% of the participants were successfully contacted for follow-up six months post discharge. Analyses focused on baseline and outcome comparisons of patients with histories of sexual assault and patients with no history of sexual assault. The prevalence of assault in the sample was 15%. Baseline measures indicated that patients in the assaulted group were more likely to have a history of suicide planning and demonstrated greater psychiatric symptom severity as measured by the Brief Symptom Inventory. Outcome measures indicated that treatment was effective for both groups in psychiatric symptom reduction and in reduction of alcohol and other drug use. Results are discussed in terms of specific treatment needs for substance abuse patients with sexual assault histories. PMID- 7884600 TI - Eye movement desensitization and reprocessing: treating trauma and substance abuse. AB - Eye Movement Desensitization and Reprocessing (EMDR) is a new psychological methodology that has been applied to a wide range of psychological disorders. Clinical reports over the past three years indicate that it is an important addition to the treatment of substance abuse. EMDR offers a structured, client centered model that integrates key elements of intrapsychic, behavioral, cognitive, body-oriented, and interactional approaches. Treatment effects are quite rapid and, during an individual session, the therapist may witness accelerated processing of information involving a shift of cognitive structures (including the assimilation of positive beliefs) along with the desensitization of attendent traumata. The application of EMDR apparently stimulates an inherent physiological processing system that allows dysfunctional information to be adaptively resolved, resulting in increased insight and more functional behavior. The judicious use of EMDR includes a comprehensive client history and extensive preparation, allowing the client to deal with the high levels of disturbance often engendered by the treatment itself. After the inauguration of a sufficient therapeutic alliance, adequately addressing potential issues of secondary gain, and appropriate client stabilization, EMDR may be used to ameliorate the effects of earlier memories that contribute to the dysfunction, potential relapse triggers, and physical cravings. In addition, EMDR is used to incorporate new coping skills and assist in learning more adaptive behaviors. Other potential targets for reprocessing include treatment noncompliance, ambivalence about abstinence, and present crises. Finally, EMDR should be used on this clinical population only by a trained clinician who is educated and experienced with this problem area. PMID- 7884601 TI - Psychology of comorbid posttraumatic stress disorder and substance abuse: lessons from combat veterans. AB - This article provides important phenomenological observations, conceptual models, research findings, theoretical ideas, and psychotherapeutic techniques that are proving useful in working with combat veterans who display both PTSD and substance abuse disorders. Some of the clinical challenges of treating patients displaying a complicated trauma response are explored, such as the phenomena of patient and therapist dichotomous thinking, a "tuned-out" patient style, and difficulty establishing or maintaining therapeutic alliance. A clinically useful model (cocomplication model) is presented that views PTSD and substance abuse as tending mutually to impede resolution of one another, so that over time the patient may never achieve significant resolution of either problem. An overview of historical and current models of PTSD is then presented in order to provide a context for understanding ways that pretrauma variables might help determine the nature, persistence, and severity of adverse psychological reactions to overwhelming stress. Pathogenic beliefs developed in response to childhood mistreatment, abuse, or neglect are capable of mediating responses to later trauma. Once reinforced in combat or by other trauma, such beliefs may become particularly tenacious and compelling. Pathogenic beliefs incompatible with recovery from the trauma response and from addiction are reviewed. Testing for safety among traumatized populations is discussed and treatment suggestions are provided to avoid confirmation of pathogenic beliefs. A clinical case is provided that illustrates the application of these concepts to formulation and treatment. PMID- 7884602 TI - Anger management and temper control: critical components of posttraumatic stress disorder and substance abuse treatment. AB - Recent studies have shown associations among combat experience, PTSD, anger and hostility, and involvement in violence. Clinical observations of veterans enrolled in the Substance Use/Posttraumatic Stress Disorder Team (SUPT) program at the San Francisco Veterans Affairs Medical Center revealed relatively high levels of anger and aggressive behavior, including physical assaults and property damage. In response to this anger and aggressive behavior, an anger management treatment was added to the SUPT program's treatment of substance abuse and PTSD. Anger management consisted of a 12-week cognitive-behavioral group treatment. Session topics included identifying the physical, emotional, and situational cues to anger, developing individualized anger-control plans, recognizing and altering destructive self-talk, utilizing time-out, practicing conflict resolution techniques, and using the group to discuss and evaluate high-risk anger situations. Special attention was given to self-monitoring anger-escalating behavior (using an anger meter) and avoiding negative consequences. This article describes the components of the anger management treatment. A clinical vignette is also presented to illustrate the benefits of anger management treatment. PMID- 7884603 TI - Adolescents in a therapeutic community: treatment implications for teen survivors of traumatic experiences. AB - This article describes an adolescent with a history of severe traumatic experiences and treatment in a residential program for chemically dependent, severely emotionally disturbed youths between the ages of 12 and 18. It begins with a description of the long-term treatment program, the types of clients admitted, and the treatment activities provided. Basic findings from an outcome study conducted within the program made predictions regarding the length of time of residential treatment for drug addicted, severely emotionally disturbed adolescents regardless of trauma history. Pretreatment psychiatric functioning was addressed by utilizing GAF scores from the DSM-III-R for each of the participants in the study. Of 102 participants in the study, 34 were survivors of sexual abuse, physical abuse, or devastating natural disasters. A clinical case of a traumatized adolescent is presented in relation to adolescent identity, the distinction between adolescent and adult treatment, and a variety of treatment strategies that can influence an abused adolescent's long-term recovery from both addiction and trauma, including retention in treatment, the developmental stage of adolescence, identification and diagnosis of trauma during adolescence, building a working alliance, individual psychotherapy, psychopharmacology as an aid to psychotherapy, psychological debriefing, and group psychotherapy. PMID- 7884604 TI - Trauma and trauma-related disorders for women on methadone: prevalence and treatment considerations. AB - There is a growing recognition of the strong association between psychoactive substance abuse and violence. Repeated exposure to violent trauma is particularly salient for women. Moreover, violent trauma may play a role in the etiologies of depression, substance abuse, and trauma-related disorders, such as posttraumatic stress disorder (PTSD). For the female methadone patient, an untreated trauma related disorder can be a hidden factor that hinders treatment response and leads to treatment complications, such as depression, polysubstance abuse, or treatment drop out. This article reviews the prevalence of trauma and violence for women on methadone, comparing low-income, inner-city female drug abusers with males in methadone treatment on childhood and adulthood exposure to violent trauma and PTSD. Because women are in a minority in methadone maintenance treatment programs, standard treatment approaches have generally not focused on their particular issues and needs. Two alternative models are presented for group treatment of trauma and trauma-related disorders in female methadone patients; potential benefits of each in reducing symptomatology and improving interpersonal functioning are examined. Modification of standard approaches and the typical barriers to engagement in treatment for this special population are also addressed. PMID- 7884605 TI - Psychological functioning and substance abuse before and after the 1992 Los Angeles riot in a community sample of women. AB - An ongoing study of interventions designed to increase nontraditional social supports among women at high risk for HIV infection was in the field during the 1992 Los Angeles riot in those neighborhoods most affected by the urban unrest. Using data from structured interviews, the psychosocial characteristics, drug abuse patterns, and distress levels among the women who were recruited for the project in the six months before and after the riot were examined. While substance abuse levels among participants did not increase or decrease as a function of the riot, there were a smaller number of social supports and marginally greater levels of already high psychological distress. Women in the community specifically mentioned a lack of social supports from counselors available in affected areas after the riot. An ethnographic analysis discusses the experience of the participants in the community during the same period of time. Problems in social supports are pointed out. The results are discussed in terms of a general theory of service provision by increasing nontraditional social supports, especially immediately after a major cataclysm. PMID- 7884606 TI - Wilson's disease treated with trientine during pregnancy. PMID- 7884607 TI - Pancreatic exocrine failure in cystic fibrosis presenting as necrotising enteritis. PMID- 7884608 TI - Rapidly progressive and fatal scleromyxedema in an adolescent with Crohn's disease. PMID- 7884609 TI - Giant hyperplastic lymphoid polyp of the intestine: a rare polypoid lesion in childhood. PMID- 7884610 TI - Take this retrovirus and call me in the morning? PMID- 7884611 TI - Liver disease in pediatric ulcerative colitis. PMID- 7884612 TI - Animal models of necrotizing enterocolitis. PMID- 7884613 TI - Difficult feeders: intervene or watch? PMID- 7884614 TI - Circulating levels of interleukin-6, interleukin-8, and tumor necrosis factor alpha in children with autoimmune hepatitis. AB - Circulating levels of the proinflammatory cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured in 13 children with autoimmune hepatitis (AIH) (seven with type 1 and six with type 2). In untreated children with type 1 AIH, TNF-alpha, IL-6, and IL-8 levels were elevated when compared to those of healthy controls (p < 0.005, p < 0.02, p = 0.06, respectively), whereas in children with type 2 AIH, cytokine levels were normal in all except one sample. A significant decrease in circulating IL-6, IL-8, and TNF-alpha was observed when patients were evaluated during a subsequent remission. We found no significant correlation of cytokine levels with alanine aminotransferase (ALT) activity, total serum gamma-globulins, or prothrombin activity. In patients with cirrhosis, serum IL-8 and IL-6 levels were higher (significantly in the case of IL-8) than those of patients without cirrhosis. In conclusion, activation of the in vivo production of the proinflammatory cytokines IL-6, IL-8, and TNF-alpha appears to be associated with type 1 but not with type 2 AIH. PMID- 7884615 TI - Reversal of Indian childhood cirrhosis by D-penicillamine therapy. AB - Serial liver biopsy changes have been reviewed in 30 patients with Indian childhood cirrhosis (ICC) who were randomly allocated to receive treatment with penicillamine in a dose of 20 mg/kg/day, 10 of whom also received prednisolone, and five receiving placebo. The latter died within 185 (mean, 149) days of starting treatment. Nine receiving penicillamine died within 540 (mean, 338) days, but the remainder are well 5.1-9.3 years after commencing treatment. Initial biopsies showed severe hepatocellular injury, pericellular fibrosis, inflammatory infiltration, and orcein-staining granules. Second biopsies taken within 6 months of starting penicillamine usually showed persistence of inflammation and an increase in nodularity with thick and thin active septae. Subsequently the appearances were of an inactive micronodular cirrhosis, with reduction in septal inflammatory infiltrate, hepatocellular injury, and intensity of orcein staining. This further improved to a stage of incomplete fibrous septae. The last liver biopsies at 6-60 months (in 21 survivors) showed almost normal histology in four, incomplete fibrous septae in five, and inactive micronodular cirrhosis with thin septae in 12. Mean liver copper concentrations decreased from 1,407 (SEM, 121) micrograms/g at presentation to 925 (183), 317 (100), and 127 (35) at 6, 6-18, and > 18 months after starting treatment. By contrast, a second biopsy taken in the 6 months after diagnosis in placebo treated children showed persistence of ICC with increase in inflammation, fibrosis, and orcein staining. PMID- 7884616 TI - A complex biochemical modulation of intestinal ion transport in rats fed on high fat diets. AB - This study investigates the relationship between dietary fat and ion transport in rat intestine. Animals were fed isocaloric diets with high fat content as corn oil, evening primrose oil (Efamol), fish oil, Efamol/fish oil, olive oil, coconut oil, and butter. A low-fat (corn oil) diet was used in a control group. Biopsies of the small intestine from these animals were mounted in an Ussing chamber, and the intestinal mucosal to serosal ion transport was measured as short-circuit current (SCC). The SCC was stimulated in rats fed on diets high in polyunsaturated fatty acids such as corn oil, Efamol, fish oil, and Efamol/fish oil. SCC was also stimulated in rats fed on diets high in monosaturated fatty acids such as olive oil. Animals fed on diets high in saturated fatty acids such as coconut oil and butter, on the other hand, showed an inhibition in the SCC. To determine whether the effect of membrane lipids was mediated by a differential effect on membrane receptor proteins, the response to secretogogue challenge was studied. Biochemical agents and secretogogues including acetylcholine, noradrenaline, dibutyryl-cAMP, calcium ionophore A2318, and prostaglandin E2 were analysed and compared. These agents were able to influence the SCC, showing responses with marked differences between diet groups. PMID- 7884617 TI - Folic acid in the prevention of neural tube defects. PMID- 7884618 TI - Quantitative analysis and immunohistochemical studies on small intestinal mucosa of food-sensitive enteropathy. AB - Quantitative analysis and immunohistochemical studies of small intestinal mucosa were performed to investigate the mechanism of mucosal damage in 10 patients with food-sensitive enteropathy. Jejunal biopsy specimens were taken before and after treatment and after clinical relapse following a challenge test. The low villous height of untreated patients normalized after introduction of an elimination diet but declined again to subnormal level after a challenge test. Several other types of cells were significantly increased in the untreated patients in comparison to controls. These included HLA-DR+ (DR+) CD4+ cells in the lamina propria and intraepithelial CD8+ cells. Moreover, those cell patterns, such as increased DR+ CD4+ cells and CD8+ cells, normalized with treatment but regressed to pretreatment levels when the patients were challenged. These findings suggest that activated CD4+ cells in the lamina propria of the small intestinal mucosa, probably by releasing cytokines, may play an important role in contributing to mucosal damage in patients with food-sensitive enteropathy. PMID- 7884619 TI - In vivo study of colonic fermentation of carbohydrate in infants. AB - Dietary carbohydrate in the colon is fermented and converted into short-chain fatty acids. We studied the fate of carbohydrate that arrives in the colon under circumstances similar to those that occur during an episode of diarrhea and determined whether a quantitative correlation exists among certain indicators of colonic fermentation of carbohydrate arriving in the large bowel. A stable isotope method was used to estimate carbon scavenging by the colon. Fourteen infants with severe malnutrition and history of watery stools and/or increased numbers of stools in the preceding 20 days were studied. Infants underwent nasocecal intubation and a 60-min infusion of 0.5 g/kg glucose containing 5 mg/kg of 13C-glucose. Stools were assessed for carbohydrate-fermenting bacteria, acetate, glucose, and 13C abundance; blood was assessed for acetate; and breath was assessed for hydrogen. Some of the infants eliminated the infusate per anus within 30 min of the infusion (group I; n = 5), while others did so 120 min or more after the infusion (Group II; n = 9). The volume of fecal output after the intracecal infusion differed significantly between group I and group II (57 +/- 13 vs. 24 +/- 4 ml; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884620 TI - Applied potential tomography in the measurement of gastric emptying in infants. AB - The aim of this study was to investigate the feasibility of using applied potential tomography (APT), a noninvasive and nonradioactive method, to measure the rate of gastric emptying in preterm babies and infants < 3 months old. APT, a form of electrical impedance tomography, creates tomographic images of tissue resistivity to a small electrical current and has been used to study gastric emptying in adults. The rate of gastric emptying of 53 preterm infants and 29 term infants was measured. The test feed was either milk (formula milk or expressed breast milk) or Dioralyte (a commercial rehydration solution). When a nasogastric tube was present, the results obtained by APT were validated by comparing the volume of feed estimated to be present with the volume that could be aspirated. All infants completed the investigation without any problems. APT demonstrated a slower rate of emptying of milk feeds than Dioralyte and showed that milk and Dioralyte feeds in preterm babies emptied at a similar rate to feeds in term infants. In validation studies, gastric emptying has been observed in 44 of 47 studies, and this finding was confirmed by aspiration of the nasogastric tube. Applied potential tomography is a safe, noninvasive method for measuring gastric emptying in small infants. PMID- 7884621 TI - Very early onset nonorganic failure to thrive in infants. AB - Nonorganic failure to thrive (NOFTT) occurs in absence of any gastrointestinal, endocrine, or other chronic diseases. It is usually associated with psychosocial deprivation, although behavior problems may also contribute to its occurrence in absence of maternal pathology. We report seven infants and children between the ages of 13 and 30 months at the time of presentation, who failed to consume adequate calories and suffered from delayed growth. All were born at term after normal pregnancies with birth weights and lengths between the 50th and 95th percentiles except in one. None had any history of perinatal problems. Decreased intake was encountered almost immediately after birth, with lack of interest in consuming adequate calories. The evaluations performed did not reveal any specific etiology for the decreased intake. None had any developmental delay nor were there any psychiatric conditions in mothers. Changes in formulas or psychologic intervention were unsuccessful in modifying feeding habits except in two infants. All were supplemented with enteral supplements (Pediasure-five, Ensure-one, and Osmolite-one). Three did not consume enough orally and needed nasogastric tube infusions with eventual placement of gastrostomy tubes in two, and the third one has continued with nasogastric infusions. A significant increase in caloric intake caused improvement in growth percentiles. Height and weight percentiles improved in all and crept into the normal curve in four and five patients, respectively. Head circumference of two stayed at < 5th percentile despite nutritional rehabilitation. Attempts at weaning off the supplements actually resulted in weight loss in all. Our data suggest that there is a critical need for early, aggressive nutritional intervention in such infants. PMID- 7884622 TI - The relationship between stool hardness and stool composition in breast- and formula-fed infants. AB - "Constipation" and "hard stools" are associated with formula feeding of both term and preterm infants and, in the latter, can lead to life-threatening complications. This study tested the hypothesis that stool hardness is related to excretion of fatty acid (FA) soaps in term infants, and in the extreme to milk bolus obstruction in premature infants. Stools (n = 44) were collected from 20 formula-fed and 10 breast-fed infants aged 6 weeks and were classified using visual charts for stool hardness on a 5-point scale (1, watery; 5, hard). Stools were analysed for nitrogen, minerals, and lipid, the latter divided between the soap and nonsoap fractions. We explored the relationship between stool hardness or solids content and stool constituents, relative to both wet and dry weight. Calcium and FA soaps were the dominant factors significantly related to stool solids and hardness score across the breast- and formula-fed groups. An 8% increase in stool dry weight FA soap content corresponded to a 1-point change in stool hardness score. Stools from formula-fed infants had a higher solids content and were classified as significantly harder than those from breast-fed infants (hardness scores, 4.0 +/- 0.5 versus 2.6 +/- 0.7, mean +/- SD) and on both a wet- and dry-weight basis contained severalfold higher levels of minerals and lipid and considerably less carbohydrate. Differences in lipids between formula- and breast-fed infants' stools were due almost entirely to FAs (mainly C16:0 and C18:0) excreted as soaps (27.7 +/- 7.5% compared to 3.1 +/- 4.1% of dry weight), suggesting the groups differed markedly in their handling of saturated FAs. An inspissated stool sample from a premature infant requiring surgical disempaction of an obstructed small intestine was found to be enriched in FA and calcium relative to the preterm formula. FA soaps, predominantly saturated, accounted for one third of the stool dry weight. These data support the hypothesis that calcium FA soaps are positively related to stool hardness; we speculate that this may, at least in part, explain the greater stool hardness in formula- versus breast-fed infants and milk bolus obstruction in preterm infants. This conclusion is consistent with the physical properties of calcium FA soaps. PMID- 7884623 TI - Human milk total lipid and cholesterol are dependent on interval of sampling during 24 hours. PMID- 7884624 TI - End-stage renal disease in a patient with cholesteryl ester storage disease following successful liver transplantation and cyclosporine immunosuppression. PMID- 7884625 TI - Production of oil-containing polyterephthalamide microcapsules by interfacial polymerization. An experimental investigation of the effect of process variables on the microcapsule size distribution. AB - Oil-containing polyterephthalamide microcapsules were prepared by the interfacial polymerization technique. The inner phase of the microcapsules consisted of a mixture of an organic solvent, toluene, and a commercial oil, santosol. Microcapsules with mean Sauter diameters in the range 0.5-20 microns were prepared by varying the rate of agitation (2000-7000 rpm) and the concentration of a poly(vinyl alcohol) stabilizer (0.1-1.0 wt% w/v), in the presence of several ionic and non-ionic cosurfactants. High agitation rates resulted in a significant reduction of the mean size of the oil droplets, although a slight increase in the breadth of the droplet size distribution was observed. High concentrations of PVA also resulted in a decrease of the microcapsule size, although the effect of stabilizer concentration was generally less important than that of the agitation speed. Finally, the effect of various ionic and non-ionic cosurfactants on the microcapsule size distribution was investigated. It was found that the addition of a cosurfactant significantly reduced the mean droplet size of the initial emulsion, leading to the formation of microcapsules in the submicron range. PMID- 7884626 TI - Microencapsulation of indomethacin by gelatin-acacia complex coacervation in the presence of surfactants. AB - Gelatin-acacia microcapsules containing indomethacin were prepared by a complex coacervation method. To improve the wetting of hydrophobic core material different surfactants, cationic benzalkonium chloride, anionic sodium lauryl sulphate (SLS) or non-ionic polysorbate 20, were used. The effects of surfactants on microencapsulation were investigated at concentrations below, at and above their critical micelle concentration (CMC) using three different stirring speeds (200, 310 and 420 rpm). A considerable fraction of the core was leached out during the dehydration of microcapsules with isopropanol when the capsules were prepared without surfactant, and especially with SLS. SLS was noted to be an unsuitable surfactant for this process of microencapsulation, and this was considered to be due to ionic complexes, solubilization of gelatin and too effective spreading of small coacervate droplets. Benzalkonium chloride enhanced encapsulation at concentrations below and at CMC, but above CMC the encapsulation was slightly decreased due to too-effective spreading of coacervate. Polysorbate 20 enhanced encapsulation with all the concentrations allowing for the formation of intact-walled microcapsules. All the microcapsules reduced in size with increasing stirring speed. The two lowest concentrations of benzalkonium chloride and all the concentrations of polysorbate 20 increased microcapsule size due to a greater amount of the colloids being available in formation of thicker walled microcapsules. The dissolution of unencapsulated indomethacin was very slow, but the drug was released quickly from all the microcapsules whether or not any type of surfactant was used. A hydrophilic wall of gelatin-acacia microcapsules in itself ensured quick wetting of hydrophobic indomethacin. PMID- 7884627 TI - Liposomal diamidine (imidocarb): preparation and animal studies. AB - Diamidine (imidocarb, 3,3'-di-imidasolin-2-yl carbonylide dihydrochloride), a babesicidal drug, was encapsulated in liposomes to reduce the toxicity of the drug and to increase its therapeutic index. Liposomes were prepared from the mixture of egg yolk phosphatidyl choline and cholesterol (1:1 molar ratio) by a reverse-phase evaporation technique. Liposomes used in the study were of diameter 1.5-2.5 microns and contained 53 mg/ml (0.125 M) of diamidine. Animal tests were performed in three animal species. The LD50 values of the liposome-encapsulated diamidine administered intravenously and intramuscularly in inbred white mice were 52 and 6000 mg/kg, respectively. The overall decrease in acute toxicity compared to that for free drug amounted to 50-fold. At a dose of 30-80 mg/kg the loposomal diamidine was satisfactorily tolerated by sheep and horses, while free diamidine is lethal to these animals at 10 mg/kg. The liposome-encapsulated diamidine had no effect on metabolic functions of the liver. After four i.m. injections of the liposomal diamidine at a dose of 30 mg/kg we observed a 10% increase in haemoglobin content and an elevation in erythrocyte count in the blood of Babesia equi-infected horses. This indicates a therapeutic effect of the liposomal form of the drug. PMID- 7884628 TI - Influence of emulsifying agents on the properties of cellulose acetate butyrate and ethylcellulose microcapsules. AB - Microcapsules of ibuprofen were prepared according to the solvent evaporation method, using two coating polymers, cellulose acetate butyrate and ethylcellulose. The influence of two emulsifying agents, polysorbat 80 and polyvinyl alcohol, on the properties of the microcapsules was investigated. The results show that type and concentration of emulsifying agent influences size distribution, drug loading and amount of free drug on the surface of the microcapsules. PMID- 7884629 TI - Slow release of chloroquine phosphate from multiple taste-masked W/O/W multiple emulsions. AB - The efficacy and safety of chloroquine as an antimalarial has contributed to the survival of millions in the past 50 years. Chloroquine is widely available, cheap, well tolerated and orally well absorbed. Therefore, it remains an important antimalarial drug. However, on oral administration, particularly to children, the unpleasant taste is a problem. This could be avoided by 'taste masked and controlled release' formulations such as multiple emulsions. Although Plasmodium falciparum has developed resistance to many antimalarial drugs, including chloroquine, resistance may be attributed, among other factors, to subclinical dosage of chloroquine from administered pharmaceutical forms. This could also be relevant in the treatment of rheumatoid arthritis. Multiple W/O/W emulsions of chloroquine phosphate were prepared. Assessment of emulsion stability showed no significant change in the system. Prolonged storage (four months) of the emulsion resulted in negligible loss of chloroquine phosphate. The results suggest, therefore, that chloroquine phosphate releases due to diffusion of the drug from the internal globules and not as a consequence of instability of the W/O/W emulsion. These characteristics are in accordance with the requirements for controlled release pharmaceuticals. Stability of multiple emulsions could have resulted from interfacial polymerization or complexion between molecules. Release assessments showed faster rates for W/O/W emulsions which had smaller internal aqueous globules and, therefore, an increased interfacial area. Furthermore, transport of high-diffusion coefficient micelles could have given a greater solute flux in these systems. PMID- 7884630 TI - Some preparative variables influencing the properties of W/O/W multiple emulsions. AB - Water-in-oil-in-water multiple emulsions of chloroquine diphosphate were prepared, using olive oil, arachis oil, Span 80, gelatin, acacia and Tween 80. Emulsifiers were employed individually or in combination. An attempt was made to correlate preparative variables with stability and drug release of multiple emulsions of roughly comparative particle size. When the emulsions were satisfactorily stabilized by the optimum blend of surfactants the rate of release varied with the nature and/or combination of emulsifiers employed. The possible effects of phase-inversion temperature, spontaneous emulsification and liquid crystal stabilization on the systems have been discussed. The mechanism probably involved complex interfacial adsorption and hydrodynamic phenomena in the presence of natural oils, co-surfactants and natural stabilizers of individual HLB number, particularly when acacia is present in the system. This could be attributed to the existence of protein in some species of acacia, since there are about 130 species of acacia, the gummy exudations of which are considered official in compendia. The protein content could be a reasonable additional specification for acacia as an emulsifier. PMID- 7884632 TI - A study on zeta potential and dielectric constant of liposomes. AB - Zeta potential and dielectric constant of the liposomes were measured to study the effect of some of the formulation factors and in vitro ageing. Sonication affects zeta potential and dielectric constant of the liposomes. The ageing study showed an increase in the dielectric constant and zeta potential of liposomes at different storage temperatures. These two electrical parameters could be useful in studying structural alterations in liposomal vesicles and system as a function of different conditions. Particle size distribution and optical density were also measured, for comparison. PMID- 7884631 TI - Effect of encapsulation of chloramphenicol in albumin microspheres on its in vitro transfer across the human placenta. AB - The possibility of reducing drug transfer across the placenta was tested in two of our previous studies. The aim of those studies was to demonstrate an alternative method of drug application during pregnancy which we think would yield a dual benefit, i.e. protecting the foetus from the harmful effects of drugs while curing the mother. The present study was planned as a continuation of the testing of the same idea and we tried to see the effect of albumin microsphere encapsulation of chloramphenicol on its transfer across the human placenta in vitro. Microspheres containing chloramphenicol were prepared according to the method previously described. The mean per cent encapsulation of chloramphenicol in albumin microspheres was found to be 42 +/- 4.3 per cent (n = 5) and the mean size of the albumin microspheres was 3.08 +/- 0.6 mm. In vitro stability of the drug-carrying microspheres was measured by dialysing them at 37 degrees C for 24 h. Chloramphenicol was released from the microspheres gradually leaving about 50 per cent of the entrapped drug in the microspheres after 1.5 h. About 20 per cent of the chloramphenicol was retained in the microspheres at 24 h postincubation. The persistence of the antibacterial effect of the released chloramphenicol is confirmed by antibiogramme tests. In the perfusions the initial free drug concentration was kept at 100 mg/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884633 TI - Autoclaving of liposomes. AB - The attempt was made to study liposome stability and oxidation under the autoclaving conditions. It was shown that after the preliminary air removal from a liposome sample there was no lipid oxidation (malonaldehyde bis(dimethyl acetate) was used as a control) and liposome content leakage during autoclaving. Liposomes with entrapped Intal remain completely intact after autoclaving for 15 min at 120 degrees C. PMID- 7884634 TI - [The interaction of Cupressus sempervirens L. proanthocyanidolic oligomers with elastase and elastins]. AB - Cupressus sempervirens L. proanthocyanidolic (O.P.C.) oligomers inhibited the esterolytic activity of pancreatic elastase with a Cl50 of 0.0075 mg/ml when a sap substrate suc(Al)3NA was used in a Tris-HCl 0.05 M buffer with a pH of 7.5. Inhibition was slightly lower when the ionic strength of the buffer was increased. Elastolytic activity was inhibited using an elastinorcein substrate with a Cl50 of 0.05 mg/ml, whatever the pH or the ionic strength of the buffer. The oligomers bound with the elastase to form a precipitant complex where a 2 mg/ml concentration of oligomers precipitated the elastase at 1 mg/ml. Insoluble elastin fixed few 150 micrograms oligomers for 1 mg of elastin but the latter was partly protected by the subsequent action of the elastase. Soluble elastin fixed a greater number of oligomers but it was the peptids of elastin enzyme hydrolysis which fixed the largest amount: around 1500 micrograms per mg. The oligomers elastin complex seems to be more stable than that of oligomers-elastase which regains part of its esterase activity. The elastic fibers seem to be protected by the O.P.C. PMID- 7884635 TI - [Standardization of propolis extract and identification of principal constituents]. AB - Preparation of a propolis extract was codified, conditions of pulverization, extraction and treatment of the extractive solution are specified. The wounds healing properties of this extract are related to flavonoids and phenolic acids, which were identified by TLC. PMID- 7884636 TI - [Systemic emulsions. 2. Use of different methods of formulation: the effect of essential oils of thyme on stability]. AB - As part of an ongoing investigation on emulsifying techniques, we studied the influence of different essential oils from Thymus vulgaris on emulsion stability. All four chimiotypes tested (geraniol, linalol, carvacrol, and thymol) caused a marked decrease in stability. This instability cannot be explained by a change in the hydrophilic lipophilic balance since the HLBc of the new oil phase (essential oil + paraffine oil) was not significantly different from that of paraffine alone. PMID- 7884637 TI - [Evaluation of medication costs in hospitalization of AIDS patients]. AB - The aim of this study was to examine the global pharmaceutical cost of AIDS patients hospitalized in a ward of infectious diseases in Marseille. They were 209 patients at various clinical stages of HIV infection receiving or not AZT or another specific drugs. All of the 319 hospitalization stays entailed a pharmaceutical cost of 1,065,593 FF for year 1990. A detailed analysis of the therapies, excepted for AZT, determined very large expenses of anti-infectious, hypnotics and other patent drugs of gastroenterology, pneumology, stomatology and toxicology. The study showed that the total drug cost increased with the hospitalization duration. PMID- 7884638 TI - [The mechanisms of binding of active drugs to polyalkylcyanoacrylate nanoparticles]. AB - Studies on colloidal carriers such as nanoparticles are generally based on the evaluation of the optimal amount of drug linked to the polymer matrix. This figure is obtained through the mathematical treatment of adsorption/incorporation isotherms. However, results of the literature show an obvious heterogeneity in the isotherms mathematical treatment. A theoretical review of the potential models of the sorption process of drugs will be used to compare the results previously published in the literature. An experimental and systematic approach will be proposed in order to compare more easily the studies from the different research teams and to evaluate the interactions between drugs and colloidal carriers. PMID- 7884639 TI - The influence of polymer concentration on the 5-fluorouracil release rate from carbopol hydrogels. AB - 5-Fluorouracil (5-FU) release kinetics from Carbopol 940 hydrogels prepared at pH 5.5 and five different polymer concentrations (0.0010, 0.0015, 0.0020, 0.0025 and 0.0030 w/w) were determined using Franz diffusion cells. Higuchi's equation for release from solutions was used to calculate the diffusion coefficients of 5-FU in the hydrogels. An empirical equation was obtained for the estimation of diffusivity of 5-FU as a function of polymer concentration, which from a practical view point can be considered useful in preformulation studies. Furthermore, the values of viscosity for all hydrogels assayed were determined. The diffusivity-viscosity relationship resembles the Stokes-Einstein equation for small solutes in liquid phases and provides a factor indicative of additional resistance offered by the gelling agent for drug diffusion. PMID- 7884640 TI - [Reaction and interactions of drugs]. PMID- 7884641 TI - The changes and significance of mast cells in irradiated rat liver. AB - There has been no report on changes in mast cells in hepatic radiation injury. Because of the interactions between mast cells and fibroblasts and mast cell changes in radiation interstitial pneumonitis, we examined the mast cells in experimental hepatic irradiation. We used 60Co gamma-ray in a single dose of 10, 30, 50, and 60 Gy given to the liver area of male Wistar rats. The liver tissue was examined 0.5, 1, 2, 3, 6, 9, and 12 months after irradiation. The mast cells were quantitatively and qualitatively assessed in liver sections by light and electronmicroscopy. Typical chronic liver fibrosis occurred after 30 Gy. As the lesions progressed in severity, the number of mast cells increased and they became larger 1 to 2 months after irradiation. After 3 to 6 months, this change was very marked and degranulation was noted. Both the number and size of mast cells were increased markedly. The peak intensity in mast cell changes paralleled that of connective tissue proliferation. At 12 months, when the fibrous tissue was rich in collagen, the mast cells decreased in number. Our findings suggest that mast cells participate in the development of radiation hepatic fibrosis. PMID- 7884642 TI - "In vitro" effects of methyl-mercury on the nervous system: a neurotoxicologic study. AB - Many of the currently prevailing toxicologic problems are due to the use of organic mercurial compounds in pesticides and fungicides. During recent years, environmental pollution has originated from the incorrect use of these organometals. Methyl-mercury (Me-Hg) is absorbed quickly from the gastrointestinal tract and is distributed to most tissues. The most important effect of Me-Hg is on the nervous tissue and is more relevant in the fetal brain. We were interested in assessing the neurotoxic effects of Me-Hg on the central and peripheral nervous system. Neuronal cells cultures from 14-day-old fetal Wistar rats and ciliary ganglion cells cultures from 8-day-old chick embryos were used. Various Me-Hg concentrations (10(-3) M to 10(-8) M) were added to these cultures after 36 hr to study the morphologic changes. At 10(-3) M and 10(-4) M concentrations, cellular degeneration and death in the central nervous system (CNS) were noted. At 10(-5) M concentrations, axonal and nerve fibers degeneration, loss of synapsis, and inhibition in the cellular development in CNS were seen; regroupment and destruction in the peripheral nervous system (PNS) was noted. Finally, at 10(-6) M and 10(-7) M concentrations, there were hardly any modifications in the CNS, whereas only the nervous processes were affected in the PNS. PMID- 7884643 TI - Sublethal effects of inorganic mercury on the body growth rate and liver function enzymes of phenobarbitone-pretreated and promethazine-pretreated rabbits. AB - Hepatotoxic effects of inorganic mercury with and without pretreatment of phenobarbitone and promethazine have been described in experiments on domesticated rabbits. The total body weight and the relative liver weight decreased after mercury treatment under all experimental conditions. After phenobarbitone (PB) treatment, the serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), isocitrate dehydrogenase (ICDH), and lactate dehydrogenase (LDH) activities decreased to 31%, 77%, 20%, and 27%, respectively, whereas the serum alkaline phosphatase (AP) activity increased 54%. After promethazine (PM) treatment, however, the serum GPT activity was inhibited 73%, whereas the serum LDH activity increased 53%. Both hepatic GPT and AP activities decreased after PB (41% and 46%, respectively) and after PM (50% and 52%, respectively) treatments, while the activities of LDH and ICDH increased (after PB: 924% and 108%, respectively; after PM: 147% and 40%, respectively). After mercuric chloride (HgCl2) treatment, the serum GOT, GPT, LDH, and ICDH activities decreased 69%, 83%, 11%, and 48%, respectively. The hepatic GOT, LDH, and AP activities increased 56%, 129%, and 51%, respectively. The administration of HgCl2 in PB-pretreated animals was associated with a decrease in the activities of serum GOT and AP (57% and 69%, respectively), while the ICDH activity increased 27%. The hepatic GOT, GPT, and AP increased 58%, 135%, and 77%, respectively, after mercury treatment, whereas LDH and ICDH were inhibited 78% and 29%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884644 TI - Inhibition of the transforming ability of cigarette smoking condensate-treated human fetal lung DNA induced by oltipraz. AB - Rat-1 cells transfected by genomic DNA of human fetal lung explants treated with 100 micrograms/ml of oltipraz (5-(2-pyrazimyl)-4-methyl-1, 2-dithiol-3-thione) for 14 hr or 100 micrograms/ml of cigarette smoking condensate for 6 hr formed 0 to 8 transformation foci, respectively. If 100 micrograms/ml of oltipraz was added to culture of human fetal lung explants 8 hr prior to the treatment of cigarette smoking condensate, the Rat-1 cells transfected by genomic DNA of human fetal lung explants formed only two foci. In addition, the growth speed of Rat-1 cells transfected by genomic DNA of human fetal lung treated with both oltipraz and cigarette smoking condensate was lower than that transfected by cigarette smoking condensate-treated human fetal lung DNA. Our results indicate that oltipraz can block the irreversible change of human fetal lung DNA caused by cigarette smoking condensate, and the results suggest the possibility of using oltipraz as control in the experimental initiation of human lung carcinogenesis. PMID- 7884645 TI - Assessment of the histopathological lesions and chemical analysis of feral cats to the smoke from the Kuwait oil fires. AB - Twenty-six adult or subadult feral cats were collected from Kuwait approximately 8 months after the ignition of the Kuwait oil wells. These animals were obtained from two sources: 12 animals from Kuwait City, a relatively smoke-free area, and 14 from the city of Ahmadi, an area with heavy smoke. Animals were euthanized and a complete set of tissues consisting of all major organs was taken for histopathology. Samples of lung, liver, kidney, urine, and blood were also taken for toxicology. Histopathological lesions observed in the lung were mild accumulations of anthracotic pigment in the lungs of 17 cats. Hyperplasia of the bronchial and bronchiolar gland in 8 cats, and smooth muscle hyperplasia of bronchioles in 14 cats. Tracheal gland hyperplasia was observed in 7 cats, and minimal squamous metaplasia of the tracheal mucosa in 17 cats, Laryngeal lesions consisted of submucosal gland hyperplasia in 2 cats and squamous metaplasia of the mucosa in 5 cats. Hyperplasia of the nasal submucosal glands was observed in 6 animals. The pharyngeal mucosa as well as other organs and organ systems were normal in all cats. Atomic absorption analysis for 11 metals was performed; vanadium and nickel levels (two metals that were present in the smoke from the oil fires) are not indicative of substantial exposure to the oil fires. Based on the histopathological findings and toxicological analysis, it is felt that inhalation of air contaminated with smoke from the oil fires had little or no long-term effect on the animals examined. PMID- 7884646 TI - Lithium: a review of its pharmacokinetics, health effects, and toxicology. AB - Lithium (Li) is commonly used in treating bipolar disease. Therapeutic concentrations of lithium have almost no psychotropic effects in normal man. It is not a sedative, depressant, or euphoriant and this characteristic differentiates lithium from other psychotropic agents. Prospective epidemiologic studies demonstrate that lithium carbonate in therapeutic oral doses with the plasma level between 1.2 and 1.5 meq/L (225 to 676 mg of lithium) do not cause diabetes insipidus, urine output increases in men to 3 liters; GFR does not significantly increase; creatinine clearance remains stable in women but decreases in men; renal concentrating capacity is significantly reduced; calcium metabolism is altered by lowering urinary calcium excretion and increasing serum calcium concentrations, thereby increasing circulating PTH. In pregnancy Li causes an increase in high perinatal death rate and a high malformation rate. The use of lithium in early pregnancy is associated with a several fold increase in the incidence of cardiovascular anomalies in the newborn, tricuspid valve abnormalities. The woman on lithium therapy who attempts to become pregnant should notify her physician. Careful monitoring of blood lithium levels must be done every three days. PMID- 7884647 TI - Enhancement by caffeine of mammary gland lobulo-alveolar development in mice: a function of increased corticosterone. AB - Previously we have reported that the stimulatory effect of caffeine on lobulo alveolar development in the mammary glands of female Balb/c mice is not due to a direct action of the drug on the mammary gland but appears to be due to a caffeine-induced alteration of a yet to be defined systemic physiological process (VanderPloeg et al., J Environ Pathol Toxicol Oncol 11:177-189, 1992). In the present study, we administered caffeine (via the drinking water, 500 mg/L) to ovariectomized, estrogen- and progesterone-treated Balb/c mice. After 30 days of caffeine treatment, a significant (p < 0.001) enhancement of lobulo-alveolar development in the mammary glands of the hormone-treated mice, compared with hormone treated control mice, was observed. Six blood components, that is, total free fatty acids (FFA), glucose, IGF-1, insulin, prolactin and corticosterone, each known to enhance normal or neoplastic mammary gland growth processes in mice or rats, were quantitatively assessed in the blood of these mice. Of these six blood components, only corticosterone (p < 0.001) increased significantly in the caffeine-treated mice. These results provide evidence that the enhancement of mammary gland lobulo-alveolar development in mice by chronic consumption of caffeine appears to be a result of caffeine-enhanced secretion of corticosterone. PMID- 7884648 TI - Chemical reagents as potential impurities of pharmaceutical products: investigations on their genotoxic activity. AB - The genotoxic activity of chemical reagents and intermediates as potential impurities of final pharmaceutical products have been investigated by the AFI Mutagenesis Study Group. A number of compounds employed in the synthesis of beta lactam (12), quinolone (6), antiviral (3), and other drugs (11) were analyzed. The information reported in this article was mainly obtained experimentally in our laboratories. In addition, attempts were made to obtain reference data; however, these were available for only a few compounds. The genetic end-point taken into account was principally gene mutation in bacteria. All chemical reagents used in the synthesis of quinolones and antivirals were negative in the Ames test. As far as reagents employed in beta-lactam synthesis were concerned, genotoxic activity was shown by the alkylating agents bromomethanol acetate and chloromethanol acetate, by carbon disulfide, and by the different dimethylanilines. The other chemicals generically considered as involved in "other syntheses" did not induce gene mutation, except for 2,5-dibromopentyl acetate, which was positive in the Ames test. For this compound, as for the halogenated methanol acetates, genotoxic activity was expected in view of its alerting chemical structure. PMID- 7884649 TI - Effects of bladder resorption on pharmacokinetic data analysis. AB - In modern pharmacokinetic analysis, the urinary bladder is usually viewed as a nonreturning compartment or storage site for renally excreted compounds. Our previous studies have indicated appreciable bladder resorption of drugs. The present study used computer simulations to evaluate the quantitative importance of several potential determinants of bladder resorption, namely the bladder resorption rate constant (ka), interval between bladder voiding (delta tvoid), ratio of renal elimination rate constant to overall elimination rate constant (ex:kel ratio), and kel or t1/2. The data identified ka, delta tvoid, and kex:kel ratio as the three most important determinants of the rate and extent of bladder resorption. We further examined the errors introduced in the derived pharmacokinetic parameters due to omission of bladder resorption. Plasma concentration-time profiles and urinary excretion-time profiles were generated by simulations using different values of ka, delta tvoid, and kex:kel ratio. These profiles were used to derive the pharmacokinetic parameters, including the renal clearance (CLrenal), total body clearance (CLtotal), nonrenal clearance (CLnonrenal), t1/2, mean residence time (MRT), amount and fraction of dose excreted in urine (Aex and fe), and volume of distribution at steady state (Vdss). Data show that resorption of drug from the bladder into the systemic circulation increased the area under the plasma concentration-time profile, MRT and t1/2, but decreased CLrenal, CLtotal, Aex, and Fe. Vdss was relatively unchanged. Overestimation of MRT and t1/2 was dependent on ka, kex:kel ratio, and delta tvoid. Underestimation in CLrenal), Aex, and fe was not dependent on the Kex:kel ratio, but was affected by changes in ka and delta tvoid. CLrenal and fe were the most sensitive pharmacokinetic parameters, with a > or = 50% underestimation at a ka value that we reported previously, for the bladder absorption of antipyrine in rats with intact urothelium. In summary, these data indicate (i) alteration in the plasma concentration-time profiles and urinary excretion-time profiles due to bladder resorption, and (ii) substantial over- or underestimation in the derived pharmacokinetic parameters due to erroneous omission of bladder resorption. PMID- 7884650 TI - Prediction of brain delivery of ofloxacin, a new quinolone, in the human from animal data. AB - We attempted to predict the delivery of ofloxacin (OFLX), a new quinolone antibacterial agent (NQ), into cerebrospinal fluid (CSF) in the human based on the physiological properties and pharmacokinetic parameters of NQs in various animals. Physiological properties for evaluation of drug delivery into CSF such as volume and the bulk flow rate of CSF and weight of choroid plexus, were compared among the rat, rabbit, cat, dog, and human. Statistically significant correlations with power values of 0.82-0.89 in the linear regression were observed on log-log plots between brain weight and those properties of each species. Delivery of OFLX into CSF from blood was analyzed by "diffusion and flow model" with unidirectional efflux process from CSF to blood. The blood-CSF diffusion clearance and the efflux clearance of OFLX in the human were extrapolated from animal data based on the allometric correlations between brain weight and these parameters in the rat, rabbit, and dog. The apparent volume of distribution and the total body clearance of NQs in the human could also be predicted from animal data based on the classical Adolph-Dedrick approach. To simulate the CSF concentration-time profile of OFLX in the human by using these predicted parameters, it was necessary to consider both the lumbar CSF compartment and the ventricular CSF compartment. Both plasma and CSF concentration-time profiles of OFLX predicted from only animal experimental data were in good agreement with those observed clinically. PMID- 7884651 TI - Identifiability and indistinguishability of nonlinear pharmacokinetic models. AB - Three nonlinear model structures of interest in pharmacokinetics are analyzed to determine whether the unknown, independent, model parameters can be deduced if perfect input-output data were available. This is the problem of identifiability. The method used is based on the local state isomorphism theorem. In certain circumstances, the modeler may be undecided between several model structures and it is then of interest to determine whether different model structures can be distinguished from perfect input-output data. This is the problem of model indistinguishability. The technique used, again based on the local state isomorphism theorem, parallels the similarity transformation approach for linear systems described previously in this journal. The analysis is performed on three two-compartment examples having one linear and one nonlinear (Michaelis-Menten) elimination pathway. In each model there is, on physiological and other grounds, some uncertainty over the precise location (central compartment or peripheral compartment) of one of the elimination pathways. PMID- 7884652 TI - Brief retrospectives in pharmacokinetics. On absorption rate and fraction absorbed. PMID- 7884653 TI - Toxicokinetics of oxazepam in rats and mice. AB - The comparative toxicokinetics of oxazepam were studied in F344 rats, B6C3F1 mice, and Swiss-Webster mice of both sexes after an i.v. dose of 20 mg/kg and oral gavage doses of 50, 200, and 400 mg/kg. In addition, the toxicokinetics of oxazepam in a 3-week dosed-feed study of male B6C3F1 mice at 125 and 2500 ppm were also investigated. Results indicated that the elimination of oxazepam from plasma after i.v. injection in both rats and mice were first-order and could be best described by a two-compartment model with a terminal elimination half-life of 4-5 h for rats and 5-7 h for mice. After oral gavage dosing the peak oxazepam plasma concentrations in most rodents were reached within 2-3.5 h. At all doses studied, female rodents had significantly higher plasma concentrations than males. Absorption of oxazepam was significantly extended at higher oral doses of 200 and 400 mg/kg. At 50 mg/kg, the bioavailability of oxazepam in rats (< 50%) was lower than in Swiss-Webster mice (> 80%). The bioavailability of oxazepam in both B6C3F1 and Swiss-Webster mice decreased with increasing dose. A dose proportionality of Cmax was not observed in rats and mice after gavage doses of 50, 200, and 400 mg/kg. Plasma concentrations of oxazepam in the dosed-feed study increased with the concentration of oxazepam in the feed, a quasi-steady-state of plasma concentrations of oxazepam was reached after approximately 4 days ad libitum exposure. In B6C3F1 mice, the estimated relative bioavailability of oxazepam from dosed feed (relative to gavage study at 50 mg/kg) was about 43%. PMID- 7884654 TI - Electrophoretic mobility of salbutamol drug powder in mixed propellant solvents. AB - The influence of lipids on the dispersion properties of micronized Salbutamol base drug in liquid fluorocarbons has been characterized by electrophoretic mobility measurements and by particle size measurements. A modified Malvern ps26 microelectrophoretic cell was employed, allowing pressurized samples to be analyzed. The measurements were carried out at 25 degrees C in 100:0, 50:50, 40:60, and 30:70 blends of trichlorofluoromethane (P11) and dichlorodifluoromethane (P12) as a function of oleic acid concentration. A limited number of measurements were also done with soybean lecithin or synthetic dipalmitoylphosphatidylcholine (DPPC). A solvent series based on the polarizability (alpha) and on the dipole moment (mu) of the solvent molecules is constructed in order to estimate the acid-base character of the propellants. The results indicate that the type and the amount of lipids and also the type of fluorocarbon mixture plays an important role in the formation of surface charge. The dispersion stability with respect to the measured particle size does not always correlate with the measured electrophoretic mobility, and hence, the surface charge cannot alone explain the dispersion stability. Instead, the wettability of the powders seems to be important as well. Positive surface charge is obtained with the oleic acid or with synthetic dipalmitoylphosphatidylcholine, but negative surface charge exists with soybean lecithin. PMID- 7884655 TI - Influence of pH and plasticizers on drug release from ethylcellulose pseudolatex coated pellets. AB - Six potential plasticizers for an ethylcellulose (EC) pseudolatex coating system (Aquacoat) were evaluated at three levels (25, 30, and 35%) to study the influence of these additives on the release of a model compound, propranolol hydrochloride, from pellets in two different media, dilute HCl and phosphate buffer, pH 7.4. For the majority of the plasticizers, the release rate decreased when larger amounts of plasticizer were incorporated into the coating. However, for the plasticizers dibutyl sebacate and dibutyl adipate, no further reduction in the release rate was observed following dissolution testing in dilute HCl when the level of plasticizer was increased from 30 to 35%. This suggests that the saturation capacity of these plasticizers in the film coating had been exceeded. The media pH was found to influence the dissolution characteristics of the coatings. Faster release rates as well as earlier curve inflection points and T50% values were observed for plasticizers evaluated in phosphate buffer. All plasticizers used were independent of pH. Correlation of the dissolution results with properties of free films indicated that slower release (more complete film formation) is associated with softer and weaker films with greater elongation. PMID- 7884656 TI - Anti-inflammatory and anti-osteoporotic activities of base-boronated nucleosides and phosphate-boronated nucleotides in rodents. AB - The 2'-deoxyribonucleoside cyanoboranes were effective anti-inflammatory agents in rodents at 2-8 mg/kg; they blocked induced edema, septic shock, and pleurisy. Overall compounds 3',5'-O-(bis- (triisopropylsilyl)-2'-deoxyinosine (1), 3',5'-O bis(triisopropylsilyl)-2'-deoxycytidine (10), N3-(cyanoboryl)-2'-deoxycytidine (11), N7-(cyanoboryl)-N2-isobutyryl- 3',5'-O-bis(triisopropylsilyl)-2' deoxyguanosine (20), and N7-(cyanoboryl)-N2- isobutyryl-5'-O-(4,4' dimethoxytrityl)-3'-O-(triisopropylsilyl)-2' -deoxyguanosine (22) were the most active when all the anti-inflammatory screens are considered. The agents also blocked both local and central pain caused by inflammation. These nucleosides blocked calcium resorption but were less effective compared to other amine carboxyboranes. The inflammation process appeared blocked by these compounds because of their effectiveness in reducing both hydrolytic lysosomal enzyme and proteolytic enzyme activities. The agents were also dual inhibitors of prostaglandin cyclooxygenase and 5'-lipoxygenase activities in leukocytes and macrophages. These agents at 10(-4) M demonstrated no specific organ toxicity to ileum mucosa cells grown in tissue culture. PMID- 7884657 TI - Whole-body autoradiographic disposition and plasma pharmacokinetics of 5,10 dideazatetrahydrofolic acid in mice fed folic acid-deficient or regular diets. AB - The effect of folic acid depletion on the tissue distribution and plasma pharmacokinetics of the oncolytic agent 5,10-dideazatetrahydrofolic acid (DDATHF) was evaluated in mice fed either folic acid-deficient or regular diets. Mice were maintained on diets for 2 weeks prior to receiving a single i.v. 30 mg/kg dose of [14C]DDATHF (tissue distribution) or DDATHF (plasma pharmacokinetics). Whole-body autoradiographic evaluation and plasma analysis for DDATHF were conducted in mice at 5 min and 6, 24, 48, 96, 120, and 168 h postdose. Radiocarbon associated with [14C]DDATHF was readily distributed to all tissues in both diet groups at the early time points and was rapidly cleared from most tissues at 24 h postdose. At the later time points, substantial amounts of radioactivity remained in liver from mice fed either diet. However, levels of radiocarbon in liver from mice fed the folic acid-deficient diet were approximately 2.5-4.2-fold the radiocarbon levels in liver from mice fed the regular diet. Similarly, plasma pharmacokinetics indicated that mice fed the folic acid-deficient diet had sustained plasma concentrations of DDATHF compared to plasma concentrations in mice fed the regular diet. These data indicated that a deficiency in dietary folic acid in mice caused increased hepatic retention of radioactivity and sustained plasma concentrations of DDATHF which are probably responsible for the observed toxicity of DDATHF in mice. PMID- 7884658 TI - Dose-dependent plasma clearance of human epidermal growth factor in rats. AB - Exogenously administered human epidermal growth factor (hEGF) shows a marked dose dependent plasma disposition in rats. In the present study, total plasma clearance (CLtotal) of hEGF was examined from the viewpoint of hepatic blood flow and accessible EGF receptors in a dosing range of hEGF from 30 to 1000 micrograms/kg. In rats in which down-regulation of EGF receptors caused a reduction in their number (50% below the normal level) (group 1), the CLtotal of hEGF was decreased only at a medium dose (100 micrograms/kg) compared to those in normal rats. In rats in which hepatic intoxication with carbon tetrachloride caused 50% reduction of both EGF receptor number and hepatic blood flow (group 2), CLtotal was decreased at low and medium hEGF doses. The decrease at a low hEGF dose was proportional to the decrease in the hepatic blood flow. In rats with reduced hepatic blood flow caused by hypothermia (group 3), CLtotal was decreased at all hEGF doses examined, and the decrease at a low hEGF dose (50 micrograms/kg) was proportional to the hepatic blood flow. The decreases of CLtotal at a medium hEGF dose in groups 1, 2 and 3 were well accounted for by the decrease of hepatic blood flow and/or EGF receptor number in a well-stirred model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884659 TI - Investigation of moricizine hydrochloride polymorphs. AB - The antiarrhythmic agent moricizine hydrochloride exhibits a single melting decomposition endotherm peak at temperatures ranging from 209 to 214.5 degrees C (Form I) when recrystallized from polar solvents, as determined by differential scanning calorimetric analysis. However, a different polymorphic form (Form II), with a differential scanning calorimetric melting-decomposition peak temperature of 190 degrees C, was generated by recrystallizing moricizine hydrochloride from nonpolar solvents. These two polymorphic forms can be reversibly converted to one another by selecting recrystallization solvents. The existence of these polymorphs was confirmed by Fourier transform IR microscopy, X-ray powder diffractometry, and solution calorimetry. Polymorphic Form I exhibited a slightly slower initial dissolution rate than Form II, which correlated well with heats of solution data (less heat needed to dissolve Form II). A simulated wet granulation process did not change the polymorphic form, suggesting that wet granulation is feasible for tablet preparation. PMID- 7884660 TI - Pharmacokinetic properties of a novel gastric proton pump inhibitor, (+/-)-2-[(4 methoxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9- yl)sulfinyl]-1H benzimidazole sodium salt, in healthy subjects. AB - The pharmacokinetics and safety of TY-11345 [(+/-)-2-[(4-methoxy-6,7,8,9 tetrahydro-5H-cyclohepta[b]pyridin-9- yl)sulfinyl]-1H-benzimidazole sodium salt], a novel gastric proton pump inhibitor, were studied in healthy male volunteers after single (20, 40, and 80 mg) and repeated oral doses (60 mg, once daily for 7 days) as enteric-coated tablet. At the single doses of 20 and 40 mg, intragastric pH was continuously monitored in each of two subjects. No abnormal findings definitely attributable to the test drug were observed throughout the study. In the single-dose study, the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve of TY-11345 increased in a dose-proportional manner. The time to reach Cmax was about 3 h after dosing and plasma concentrations declined thereafter with a half-life of about 1 h irrespective of dose. The effect of food intake on the pharmacokinetic parameters of TY-11345, which was evaluated at the dose of 40 mg in a cross-over design, was not significant. TY-11345 was not detected in urine unchanged, while a main metabolite and its conjugate were identified in urine as 32-38% of the dose. An intragastric pH value over 4 was obtained about 3 h after the administration of 40 mg and maintained for more than 5 h, despite the fall of plasma concentration. This effect was less obvious at a dose of 20 mg. In the multiple-dose study, the pharmacokinetics exhibited no substantial difference between the first and last doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884661 TI - Decomposition of clozapine N-oxide in the qualitative and quantitative analysis of clozapine and its metabolites. AB - Pooled plasma from healthy volunteers was spiked with pure, synthetic clozapine or clozapine N-oxide and then made alkaline with either sodium hydroxide or sodium carbonate. The alkalized samples were allowed to stand at room temperature for various time intervals before extraction with organic solvent and then analyzed by high-performance liquid chromatography. It was found that clozapine N oxide was reduced to clozapine in plasma made alkaline with sodium hydroxide, but such reduction was negligible in the plasma made alkaline with sodium carbonate. The amount of clozapine produced from clozapine N-oxide depended upon both the strength of the alkali added to the plasma and the duration of exposure of the plasma proteins plus clozapine N-oxide to the alkali. The reduction appears to take place through reducing equivalents generated by the action of strong alkali on plasma proteins. The thermal lability of clozapine N-oxide during gas chromatography-mass spectrometric analysis was also investigated. It was found that clozapine N-oxide was quantitatively decomposed to clozapine during gas chromatography-mass spectrometric analysis. PMID- 7884662 TI - Solubilization of nicardipine hydrochloride via complexation and salt formation. AB - The solubility behavior of nicardipine (1,4-dihydro-2,6-dimethyl-4-(3 nitrophenyl)-3,5-pyridinedicarboxylic+ ++ acid methyl 2-[methyl(phenyl methyl)amino]ethyl diester), a calcium channel blocker, used in the treatment of chronic stable angina and mild essential hypertension was investigated. Two techniques that are known to improve solubility, complexation and salt formation, were examined. Concentrations were determined with a specific reversed-phase HPLC assay. The solubility of nicardipine hydrochloride was enhanced exponentially via complexation with aliphatic carboxylic acid buffer systems in a pH dependent fashion. The solubility increased from 5 to 68.6 and 270 mg/mL as the acetate or propionate buffer concentrations, respectively, increased from 0.001 to 5 M, showing a positive deviation from linearity. The conversion of nicardipine hydrochloride to the phosphate salt resulted in a approximately 10-fold solubility improvement. The surface tension of the nicardipine phosphate in water as a function of concentration indicated a critical micelle concentration of 5-6 mg/mL. The critical micelle concentration was greater than the equilibrium solubility of the hydrochloride salt in water, suggesting that a self-association phenomena is responsible for the enhanced solubility of the phosphate salt. Both routes provided potential alternatives for the solubilization of nicardipine. PMID- 7884663 TI - Pharmacodynamics and relative bioavailability of cabergoline tablets vs solution in healthy volunteers. AB - The effect of formulation on the urinary pharmacokinetics, pharmacodynamics, and relative bioavailability of cabergoline was investigated. Twelve healthy female volunteers, aged 23-35 years, were treated, according to an open, randomized, crossover design, with cabergoline (1-mg single oral dose) both as tablets and as a solution. The two administrations were separated by a 4-week wash-out period. Cabergoline and prolactin were measured in urine and plasma, respectively, by specific radioimmunoassays. Blood samples were collected before and up to 30 days after dosing. Urine was collected before and up to 8 days after dosing. Cabergoline elimination half-lives calculated from urinary data were 68 and 63 h after administration of the tablets and the solution, respectively. Urinary excretion of unchanged cabergoline accounted, on average, for 1.92% (range, 0.14 3.26) and 1.80% (range, 0.67-3.09) of the dose after administration of the tablets and the aqueous solution, respectively. Relative bioavailability of tablets vs solution was 99% (geometric mean with the 90% confidence intervals of 68-144%). Prolactin levels in 10 out of 12 subjects fell below the detection limit of the assay (1.5 micrograms/L) after both treatments. The mean maximum prolactin decrease (ca. 70%) was achieved by 2 or 3 h after dosing; the effect persisted up to 9 days, being completely exhausted 23-28 days after dosing. The analysis of variance performed on the pharmacodynamic effects of the two cabergoline formulations indicated that the percent decreases of plasma prolactin levels were not significantly different for tablets and solution. These results indicate that the pharmacodynamics and relative bioavailability of cabergoline are not influenced by formulation, as tablets or solution. PMID- 7884664 TI - Substituted 2-benzothiazolamines as sodium flux inhibitors: quantitative structure-activity relationships and anticonvulsant activity. AB - Thirty-two aryl-substituted 2-benzothiazolamines have been tested for their ability to modulate sodium flux in rat cortical slices. A QSAR analysis, applied to these derivatives, showed a trend toward increasing potency as sodium flux inhibitors with increasing lipophilicity, decreasing size, and increasing electron withdrawal of the benzo ring substituents. Additionally, 4- or 5 substitution of the benzo ring was found to decrease potency. The combination of increased lipophilicity, small size, and electron withdrawal severely limited which groups were tolerated on the benzo ring, thus suggesting that the optimal substitution patterns have been prepared within this series. Nine of these compounds were potent inhibitors of veratridine-induced sodium flux (NaFl). These nine compounds also proved to be anticonvulsant in the maximal electroshock (MES) assay. Fourteen additional 2-benzothiazolamines demonstrated activity in the MES screen, yet exhibited no activity in the NaFl assay. These derivatives may be interacting at the sodium channel in a manner not discernible by the flux paradigm, or they may be acting by an alternative mechanism in vivo. PMID- 7884665 TI - Kinetics of drug action in disease states. XLIII: Potentiating effect of L tryptophan on the hypnotic action of phenobarbital and ethanol in rats. AB - The essential amino acid L-tryptophan has been widely used as a sleeping aid because it can produce drowsiness and decrease sleep latency. Its concentrations in plasma and brain and its binding to plasma protein are markedly altered in hepatic encephalopathy and renal failure. The purpose of this investigation was to determine if L-tryptophan can enhance the sensitivity of the central nervous system to the hypnotic actions of a barbiturate and an alcohol. Female rats weighing approximately 200 g received an intravenous infusion of L-tryptophan (0.8 or 0.08 mg/min) for 30 min and then an infusion of phenobarbital (0.824 mg/min) with L-tryptophan (0.8 or 0.08 mg min-1) until the onset of loss of righting reflex (LRR). Control animals received an infusion of saline solution for 30 min and then phenobarbital without the amino acid. Similar experiments were performed with ethanol (16.3 mg/min), with and without L-tryptophan (0.8 mg/min). L-Tryptophan infused alone at a rate of 3.8 mg/min for 84 min did not cause LRR. Administration of L-tryptophan at a rate of 0.8 mg/min with phenobarbital was associated with statistically significant reductions in the total dose and concentrations of phenobarbital in serum, serum water, brain, and cerebrospinal fluid (CSF) at onset of LRR. The 0.08 mg/min infusion of L tryptophan had a less pronounced effect, with statistically significant reductions of phenobarbital concentrations at onset of LRR in brain and CSF. L Tryptophan also significantly reduced the total dose and the concentrations of ethanol in serum, brain, and CSF required to produce LRR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884666 TI - Infrared, raman, and 13C NMR spectra of two crystalline forms of (1R,3S)-3-(p thioanisoyl)-1,2,2-trimethylcyclopentanecarboxylic acid. AB - A comparative structural analysis of the two polymorphic forms of (1R,3S)-3-(p thioanisoyl)-1,2,2-trimethylcyclopentanecarboxylic acid has been performed with infrared, Raman, and 13C NMR spectroscopy. The results are compared with those of the crystallographic and thermal studies on the two forms published in previous papers. The enantiotropism of the polymorphs as well as the differences in the conformation of the carboxyl group and the resulting intermolecular hydrogen bonds were confirmed by the infrared and Raman studies. PMID- 7884667 TI - Viscoelastic properties of poly(ethylene oxide) solution. AB - The viscoelastic properties of poly(ethylene oxide) (PEO) solution were investigated using the dynamic oscillatory testing technique. With this technique, the effect of PEO molecular weight (MW), concentration, composition of mixed solvent systems consisting of propylene glycol, glycerol formal, and water, and the effect of NaCl salt on the viscoelastic properties of PEO solution were determined. Dynamic moduli (G1, G2), magnitude of complex viscosity (magnitude of eta*), and loss tangent (tan delta) were examined over a frequency range of 10( 3)-2.5 Hz at 30 degrees C. The results indicated that low MW PEOs show liquidlike behavior while high elasticity is exhibited by high MW PEOs due to entanglement formation. The complex viscosity, magnitude of eta*, exhibits shear thinning (power-law) characteristics under oscillatory measurements. The relationship between steady shear and complex viscosities follows the Cox-Merz rule over the shear rate and frequency region studied. Both the storage (G1) and loss (G2) modulus increase drastically as the proportion of water in the mixed solvent system increases. Similarly, both G1 and G2 are found to increase while the tan delta decreases with increasing concentration of PEOs. The addition of up to 2% w/w NaCl in an aqueous solution of 10% w/w 2 million MW PEO has no observed detrimental effect on the viscoelastic behavior. PMID- 7884668 TI - Hydrogen bonding. 30. Solubility of gases and vapors in biological liquids and tissues. AB - The general solvation equation log L = c + rR2 + pi H2 + a alpha H2 + b beta H2 + l log L16 has been used to analyze the solubility of solute gases and vapors, as log L values, in water, blood, and a variety of other biological fluids and tissues. The explanatory variables are R2, the solute excess molar refraction; pi H2, the solute dipolarity/polarizability; alpha H2 and beta H2, the solut hydrogen-bond acidity and basicity; and log L16, where L16 is the solute Ostwald solubility coefficient of hexadecane. The obtained coefficients then serve to characterize the biological phase as follows: r + s is the phase dipolarity/polarizability, a is the phase hydrogen-bond basicity, b is the phase hydrogen-bond acidity, ald l is the phase lipophilicity. In addition to characterization of phases, the equation can be used to determine quantitatively solute/phase interactions and predict further log L values. A similar equation in which McGowan's characteristic volume, Vx, replaces the log L16 descriptor can be used to analyze partitions between phases. For example, water/phase and blood/phase partition coefficients are analyzed, and the analysis leads again to coefficients that characterize phases and to the prediction of partition coefficients. PMID- 7884669 TI - Isoxazoles. 9. Degradation kinetics of 4-(isoxazolylamino)-1,2-naphthoquinone in acidic aqueous solution. AB - The degradation kinetics of N-(5-methyl-4-isoxazolyl)-4-amino-1,2-naphthoquinone (1) was studied in aqueous solution over a pH range of 0.65-7.50, at 35 degrees C and at a constant ionic strength of 0.5. The degradation rates were determined by high-pressure liquid chromatography and were observed to follow pseudo-first order kinetics with respect to the concentration of 1. The pH-rate profile was linear with slope -1 under acidic pH, becoming pH independent from 3.50 to 7.50. Good agreement between the theoretical pH-rate profile and the experimental data supports the proposed degradation process. The catalytic rate constants for hydrogen ion and water were kH = 0.901 M-1 h-1 and k0 = 1.34 x 10(-3)h-1, respectively. These data are appropriate to develop a stable dosage form of 1. The accuracy, peak sharpness, and asymmetry factor for the analytical method were determined. PMID- 7884670 TI - A double Weibull input function describes the complex absorption of sustained release oral sodium valproate. AB - The pharmacokinetics of valproic acid after oral administration of sustained release formulations were studied in 12 healthy volunteers. The objective of the present study was to find an appropriate mathematical model to describe the complex drug intake process. The concentration of valproic acid in plasma was measured by HPLC. For each subject, during the input process a double peak phenomenon was observed, the plasma concentrations were fitted according to a single or a double Weibull input function, and then a first-order elimination rate was used to describe the observed data. The Weibull model was considered as an approximation of the overall process. The mean peak plasma concentration, 34.6 +/- 8.9 mg/L, was reached after 8.6 +/- 2.7 h. A single Weibull function adequately described the observed data for three subjects; the mean Weibull parameters were td (the time necessary to transfer 63% of the administered drug into the systemic circulation) of 7.87 +/- 3.53 h and gamma (shape) of 1.16 +/- 0.66. A double Weibull input function was used for nine subjects; the mean Weibull parameters were td1 = 2.35 +/- 1.18 h and td2 = 9.36 +/- 4.47 h and gamma 1 = 1.77 +/- 2.27 and gamma 2 = 3.68 +/- 3.26. The mean half-life value of the elimination phase was 14.4 +/- 4.6 h. PMID- 7884671 TI - Enhancement of intestinal insulin absorption by bile salt-fatty acid mixed micelles in dogs. AB - The pharmacokinetics and pharmacodynamics of porcine zinc insulin following intravenous (iv), intrajejunal, and ileocolonic delivery were evaluated in dogs. The concentration-time profile of plasma immunoreactive insulin following iv injection could be best described by a two-compartment model with a mean distribution half-life of 1.1 min and a mean elimination half-life of 5.6 min. Maximum hypoglycemia occurred at 15 min after injection. Intrajejunal administration of 10 units/kg insulin in phosphate-buffered saline resulted in minimal insulin absorption or hypoglycemia. Incorporation of mixed micelles containing 30 mM sodium glycocholate and 40 mM linoleic acid significantly improved enteral insulin absorption. When delivered with mixed micelles, the mean absolute bioavailability of insulin was 1.8%. To study the effect of intestinal site on insulin uptake, the same formulation was delivered to the ileocolonic region. The mean absolute bioavailability of insulin absorbed from this site was 0.6%. Delivery of insulin to both sites caused significant hypoglycemia in all dogs. Insulin combined with mixed micelles is enterally absorbed in dogs; however, the bioavailability is much lower than that observed in similar studies with rats. PMID- 7884672 TI - Solvent- and concentration-dependent molecular interactions of taxol (Paclitaxel). AB - Taxol (paclitaxel) is a promising anticancer agent that has been approved for the treatment of ovarian cancer and is under investigation for the therapy of other tumors. Paclitaxel is poorly soluble in water, and information on its physical behavior in hydrophilic and hydrophobic environments is limited. Circular dichroism (CD) and nuclear magnetic resonance spectroscopy were used to investigate the effect of solvent and drug concentration on the solution conformation of paclitaxel. CD is sensitive to paclitaxel's environment, owing to the presence of effective chromophores in the vicinity of several chiral centers. It was found that (i) the conformation of the paclitaxel side chain depends on the polarity of the solvent and (ii) paclitaxel has a tendency to undergo concentration-dependent aggregation in solvents such as chloroform. To account for the observations, a model is proposed in which paclitaxel molecules are held together in stacks by intermolecular hydrogen bonds involving all four exchangeable protons. Intermolecular interactions and self-association of paclitaxel may have impact not only on the physical stability of the drug in existing formulations or investigational vehicles but also on the effect of paclitaxel in the stabilization of cellular microtubules. PMID- 7884673 TI - A prodrug approach to increasing the oral potency of a phenolic drug. 1. Synthesis, characterization, and stability of an O-(imidomethyl) derivative of 17 beta-estradiol. AB - An O-(saccharinylmethyl) prodrug was synthesized to improve the poor oral potency of the phenolic drug 17 beta-estradiol. This O-(imidomethyl) type of prodrug was designed to undergo chemical hydrolysis and to be a poor substrate for enzymatic hydrolysis. At 37 degrees C, it was found to exhibit half-lives of about 13 min in 50% methanol:pH 7.0 (v/v) phosphate buffer, about 3 min in rat plasma, about 15 min in human plasma, and about 50 min in 20% rat liver homogenate. Introduction of the enzyme poison tetraethyl pyrophosphate or the protein denaturant sodium fluoride into rat plasma had no significant effect on the half life. Thus, the observed increased rate of hydrolysis in biological media is not due to enzymatic catalysis but to a nonspecific solventlike effect. The fact that the rate of hydrolysis in the methanol:buffer exhibited a first-order dependence on the hydroxide ion concentration and that the rate of hydrolysis increased with increasing methanol concentrations up to 70% supported an SN2 mechanism of hydrolysis for the prodrug. These results suggest that an O-(imidomethyl) type prodrug is insensitive to enzymatic catalysis of hydrolysis yet may hydrolyze quickly enough to release 17 beta-estradiol faster than 17 beta-estradiol is conjugated and excreted. PMID- 7884675 TI - Microscale determination of dissociation constants of multivalent pharmaceuticals by capillary electrophoresis. AB - Dissociation constants (pKaS) of acidic, basic, and amphoteric pharmaceuticals were exactly determined by capillary electrophoresis. A general equation for use in calculation of pKaS from solute mobilities observed at different pHs was derived to be suitable for a multivalent compound with close pKaS such as angiotensins, which are bioactive octa- or decapeptides. The obtained pKa values were highly consistent with the values determined by conventional methods. For verapamil, the detection limit was 9.8 microM (49 fmol), the total analysis time was 12 min, and the relative standard deviation of the obtained pKa value was 0.11%. This method was also applicable to a mixture of two components, e.g., a bioactive compound and the prodrug, because they have different mobilities and are separated from each other. PMID- 7884674 TI - Modulated drug release using iontophoresis through heterogeneous cation-exchange membranes. 2. Influence of cation-exchanger content on membrane resistance and characteristic times. AB - An implantable drug delivery method using iontophoresis through cation-selective membranes was further developed. Heterogeneous cation-exchange membranes (HCMs) were prepared by mixing conductive sulfonated polystyrene beads into a nonconductive silicone rubber matrix. The membrane resistivity and lag time to steady-state transport of two salts, (+/-)-phenylpropanolamine hydrochloride (PPA) and NaCl, were evaluated during constant current iontophoresis at 37 degrees C as a function of the resin content in the HCMs. A continuous decline in membrane resistivity was observed as fractional resin content (l) was increased over the entire usable region (l = 0.29-0.52), a characteristic that could be described by a percolation scaling law (for an infinite lattice, 3-D geometry). Morphological analysis of the membranes before and after swelling strongly suggested that the conducting clusters of resin beads form during the swelling period prior to use. The response time to steady-state transport of PPA into NaCl during a 40 microA constant current (0.27 cm2) was found to increase with increasing l, but not without decreasing the permselectivity of the HCMs for the drug cation. The lag time effect could be explained in terms of an increasing number of fixed charge groups in the membrane available for transport (mfcA), which was derived from a macroscopic mass balance model. The values of mfcA were also found to be related to the characteristic time of diffusion in a homogeneous transport projection of the HCM (or an effective medium), an essential parameter for future non-steady-state simulations. The characteristic time of diffusion was found to be invariant with changing resin content, suggesting that the membranes are fairly nontortuous (ca. seven beads thick). By assuming that the thickness of the HCM approaches the thickness of its homogeneous projection, an expression was derived to predict lag time to steady-state PPA transport requiring resistance measurements only (provided that the resin capacity is known). There was excellent agreement between the theoretical and experimental lag time to steady state transport of PPA (r = 0.96, p < 0.001), further implicating the role of membrane resistance in the bi-ionic system. These modeling approaches have already found utility in iontophoretic implant design for prevention of cardiac arrhythmias and may be valuable in future non-steady-state analysis to further develop on-line detection-implant response technology. PMID- 7884676 TI - Relative influence of ethanol and propylene glycol cosolvents on deposition of minoxidil into the skin. AB - Minoxidil, a potent antihypertensive, is moderately effective in the treatment of hair loss when it is applied to the scalp as a 2% solution in 60% ethanol, 20% propylene glycol and 20% water. Important questions remain concerning both the mechanism of delivery and the pathway of penetration of this drug from its ternary solvent system. Since preliminary studies in our laboratory indicated that water in the formulation influenced permeation far less than the other two solvents, we examined the relative deposition and penetration influences of binary combinations of ethanol and propylene glycol. When 50 microL/cm2 of the formulations was spread over hairless mouse skin sections mounted in Franz diffusion cells, only small amounts of minoxidil were actually recovered from the receiver compartments. Nevertheless, more minoxidil penetrated the skin as the proportion of ethanol in the mixtures was increased. To determine if these in vitro results formed a representative picture of the in vivo behaviors of these vehicles, selected deposition experiments were performed on live, anesthetized mice under experimental conditions similar to those used in the diffusion cell work. The good agreement between in vivo and in vitro studies may be a result of the relatively fast partitioning of the drug into the skin as compared to its diffusion through the skin. PMID- 7884678 TI - Influence of intrarenal metabolism on the analysis of renal drug transport mechanisms. PMID- 7884677 TI - Substituent contributions to the transport of substituted p-toluic acids across lipid bilayer membranes. AB - The fluxes of p-toluic acid and seven alpha-methylene-substituted analogs have been determined as a function of pH across planar egg lecithin/decane bilayers to construct a set of well-isolated polar functional group contributions to the free energy of transfer from water to the bilayer transport barrier domain. Nonlinear regression analyses of flux-pH profiles using a model which accounts for unstirred layer effects yielded membrane permeability coefficients (PRX) that varied from 1.1 cm/s for p-toluic acid to 4.1 x 10(-5) cm/s for the alpha carbamoyl-p-toluic acid. Bulk organic solvent/water partition coefficients (KRX) were obtained for the same set of permeants using four solvent systems to identify a bulk solvent which closely resembles the chemical nature of the bilayer barrier microenvironment for these permeants. The slopes of plots of log PRX vs log KRX were 0.85, 0.91, 0.99, and 2.4, respectively, for hexadecane/water, hexadecene/water, 1,9-decadiene/water, and octanol/water with the best model solvent being that which yielded a slope closest to unity. A significant deviation in the slope from 1, as observed in the correlation with octanol/water partition coefficients, reveals that this relatively polar, hydrogen-bonding solvent is a poor model solvent for describing the barrier microenvironment for these permeants. Thus, the polar interfacial regions occupied by phospholipid head groups are not the barrier domain for the transport of the series examined in this study. The incremental group contributions to the free energy of transfer to the barrier domain (cal/mol) for the functional groups, CI, OCH3, CN, OH, COOH, and CONH2, were found to be 325, 687, 2170, 3860, 5170, and 6060, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884679 TI - Assessment of the metabolic chiral inversion of suprofen in rat by gas chromatography-mass spectrometry combined with a stable isotope technique. PMID- 7884680 TI - [Method of membrane capacitance measurements]. PMID- 7884681 TI - [Application of patch-clamp techniques for isolated newborn rat brain stem-spinal cord preparations]. PMID- 7884682 TI - [The nature of the external ionic modulation of the myocardial electrical propagation: importance of the safety factor]. AB - The mechanisms of conduction change depending on the extracellular K+ and Ca2+ concentrations ([K+]o and [Ca2+]o, respectively) were investigated. Simultaneous measurements of active and passive membrane properties and net membrane excitability were fulfilled by arranging the intra- and extracellular microelectrodes in a superfused and paced guinea pig papillary muscle. Internal longitudinal resistance (ri), as a parameter of passive property, was evaluated by the intra- and extracellular voltage ratio. The maximum upstroke rate (Vmax) was used as an active property. Apparent threshold potential (Vth) was defined by the breakpoint in the action potential upstroke fitted semilogarithmically. Graded rise in [K+]o (from 2.7 to 15.0 mM) evoked a progressive fall in Vmax, and was associated with less negative resting membrane potential and constant ri. Conduction velocity (theta) was the maximum in 9.0 mM [K+]o ("supernormal" conduction) but not in 2.7 mM [K+]o which gave the greatest Vmax ("subnormal" conduction). Safety factor of conduction (S), as an index of net excitability, could most readily account for the [K+]o-dependent change in theta. This was true also in the case of [Ca2+]o elevation (from 0.9 to 5.4 mM). These results indicate that the cation-modulated propagation is governed by the cable theory including S as a matrix of combined active and passive properties. PMID- 7884683 TI - Circadian modulation in photic induction of Fos-like immunoreactivity in the suprachiasmatic nucleus cells of diurnal chipmunk, Eutamias asiaticus. AB - Photic induction of immediate early genes including c-fos in the suprachiasmatic nucleus (SCN) has been well demonstrated in the nocturnal rodents. On the other hand, in diurnal rodents, no data is available whether the light can induce c-fos or Fos in the SCN. We therefore examined whether 60 min light exposure induces Fos-like immunoreactivity (Fos-lir) in the SCN cells of diurnal chipmunks and whether the induction is phase dependent, comparing with the results in nocturnal hamsters. We also examined an effect of light on the locomotor activity rhythm under continuous darkness. Fos-lir was induced in the chipmunk SCN. The induction was clearly phase dependent. The light during the subjective night induced strong expression of Fos-lir. This phase dependency is similar to that in hamsters. However, unlike in hamsters, the Fos-lir was induced in some SCN cells of chipmunks exposed to light during the subjective day. In the locomotor rhythm, on the other hand, the light pulse failed to induce the phase shift at phases at which the Fos-lir was induced. These results suggest that the photic induction of Fos-lir in the diurnal chipmunks is gated by a circadian oscillator as well as in the nocturnal hamsters. However, the functional role of Fos protein may be different in the diurnal rodents from in the nocturnal rodents. PMID- 7884684 TI - Normal glomerular organization of the antennal lobes is not necessary for odor modulated flight in female moths. AB - A prominent hypothesis for the function of the glomerular structures in the primary olfactory neuropil of many groups of vertebrate and invertebrate animals is that they enable the processing and coding of information about the chemical compounds that compose complex odors. Previous studies have indicated that various degrees of glomerulus formation in the antennal lobes of the brain of the moth Manduca sexta can be effected by reducing the number of olfactory sensory axons that grow from the antenna into the antennal lobe during metamorphosis. To test the hypothesis that the presence of glomerular structure is necessary to process and identify odors, we substantially reduced, by surgery, the number of antennal segments in developing moths and upon metamorphosis we observed and quantified behavioral responses known to be elicited by odors. Intact and lesioned adult female moths were challenged to fly upwind to the source of an attractive host-plant odor in a wind tunnel. Some of the moths that had developed with reduced olfactory input flew upwind to the odor source. The flight behavior of these individuals was similar to the odor-mediated flight typically observed in moths that had developed normally. Histological analysis of the moths' antennal lobes revealed that the lobes of more than half of the respondents that had been lesioned during development lacked normal glomerular organization. The neuropil of these abnormally developed antennal lobes was mostly aglomerular, but with a few isolated, clearly abnormal glomerulus-like structures. This suggests either that even a few abnormal glomeruli are sufficient to mediate this specific behavior or that "canonical" glomerular organization per se is not necessary for this odor-mediated behavior. PMID- 7884686 TI - Intracellular chloride activity of leech neurones and glial cells in physiological, low chloride saline. AB - Leech blood apparently contains considerably less chloride than generally used in physiological experiments. Instead of 85-130 mM Cl- used in experimental salines, leech blood contains around 40 mM Cl- and up to 45 mM organic anions, in particular malate. We have reinvestigated the distribution of Cl- across the cell membrane of identified glial cells and neurones in the central nervous system of the leech Hirudo medicinalis L., using double-barrelled Cl(-)- and pH-selective microelectrodes, in a conventional leech saline, and in a saline with a low Cl- concentration (40 mM), containing 40 mM malate. The interference of anions other than Cl- to the response of the ion-selective microelectrodes was estimated in Cl(-)-free salines (Cl- replaced by malate and/or gluconate). The results show that the absolute intracellular Cl- activities (aCli) in glial cells and neurones, but not the electrochemical gradients of Cl- across the glial and the neuronal cell membranes, are altered in the low Cl-, malate-based saline. In Retzius neurones, aCli is lower than expected from electrochemical equilibrium, while in pressure neurones and in neuropil glial cells, aCli is distributed close to its equilibrium in both salines, respectively. The steady-state intracellular pH values in the glial cells and Retzius neurones are little affected (< or = 0.1 pH units) in the low Cl-, malate-based saline. PMID- 7884685 TI - Effects of load inversion in cockroach walking. AB - To examine how walking patterns are adapted to changes in load, we recorded leg movements and muscle activities when cockroaches (Periplaneta americana) walked upright and on an inverted surface. Animals were videotaped to measure the hindleg femoro-tibial joint angle while myograms were taken from the tibial extensor and flexor muscles. The joint is rapidly flexed during swing and extended in stance in upright and inverted walking. When inverted, however, swing is shorter in duration and the joint traverses a range of angles further in extension. In slow upright walking, slow flexor motoneurons fire during swing and the slow extensor in stance, although a period of co-contraction occurs early in stance. In inverted walking, patterns of muscle activities are altered. Fast flexor motoneurons fire both in the swing phase and early in stance to support the body by pulling the animal toward the substrate. Extensor firing occurs late in stance to propel the animal forward. These findings are discussed within the context of a model in which stance is divided into an early support and subsequent propulsion phase. We also discuss how these changes in use of the hindleg may represent adaptations to the reversal of the effects of gravity. PMID- 7884687 TI - The homicidal patient: when a plan of care violates standards of care. AB - 1. The nursing care of an extraordinarily dangerous patient may necessitate implementing a treatment plan that should never be used under normal circumstances. 2. The subject whose case is described in this article presented management problems that required a plan violating accepted standards of care. 3. Although ultimately successful, the plan's restrictive mode (and the stress of coping with this patient) wearied nursing staff members and caused divisions among the staff and multidisciplinary team. PMID- 7884688 TI - A report on staff injuries and ambulatory restraints: dealing with patient aggression. AB - 1. During a 6 1/2-year period on a unit designed for repetitively aggressive male patients, nursing staff members were the recipients of 95% of aggressions and 97% of serious injuries. 2. Two-point ambulatory restraints, called Preventive Aggression Devices (PADS) help liberate the patient from prolonged seclusion, but in a safe manner. 3. Patient aggression is underreported; there is a need for a standardized aggression reporting system across facilities. PMID- 7884689 TI - Health care reform: clinical implications for inpatient psychiatric nursing. AB - 1. Shorter hospitalizations and increasing acuity have had an impact on all areas of inpatient services, making it necessary for health care providers to adapt quickly in order to remain competitive and continue to be able to provide quality services. 2. New modalities are being incorporated rapidly into existing units in an attempt to meet the changing needs of today's health care environment. These new programs greatly alter the traditional milieu and require a different treatment approach. 3. Inpatient hospitalization requires a rapid progression through three phases of treatment: assessment, stabilization, and discharge planning. The psychiatric nurse is instrumental in all three phases. PMID- 7884690 TI - Suicidal ideation and child abusers. Three case studies. AB - 1. Although the topic of the treatment of child abusers does not evoke much sympathy in the public or the mental health profession, the solution to this problem does not lie in hoping that all abusers should commit suicide--or that suicide is a deserved outcome for the abuser. 2. Our first priority is and should remain the child's safety; however, in too many cases the abuser-perpetrator is inextricably linked to the child, and whatever happens to the abuser may have consequences for the child. 3. It is hoped that the skewed punitive view of the abuser will change as we better understand the dynamics among violence, depression, and child abuse in our society. We could then offer the victim and perpetrator better treatment and improve our preventive strategies. PMID- 7884691 TI - What are some of the issues facing the mental health nurse in providing care to the clients who are HIV-positive or who have AIDS? PMID- 7884692 TI - Adolescent HIV prevention campaign established. PMID- 7884693 TI - A special population: grandmother caregivers. PMID- 7884694 TI - Parental alienation syndrome. A developmental analysis of a vulnerable population. AB - 1. Parental alienation syndrome is the systematic denigration by one parent of the other parent with the intent of alienating the child. 2. Parents who engage in alienating activity have experienced loss, leading to depression, anger, and aggression. The family system experiences loss during divorce and is adversely affected by the alienating activities of one parent. 3. Understanding the dynamics of parental alienation syndrome will position the nurse to recognize it as a symptom of depression and dependence, and bring care to the vulnerable population. PMID- 7884695 TI - Purchasing research from or for the NHS? PMID- 7884696 TI - Purchasing research from or for the NHS. PMID- 7884698 TI - Purchasing research from or for the NHS. PMID- 7884697 TI - Purchasing research from or for the NHS. PMID- 7884699 TI - Purchasing research from or for the NHS. PMID- 7884700 TI - Purchasing research from or for the NHS. PMID- 7884701 TI - Purchasing research from or for the NHS? PMID- 7884702 TI - Good allergy practice. Standards of care for providers and purchasers of allergy services within the National Health Service. Summary of new recommendations by the Royal College of Physicians and the Royal College of Pathologists. PMID- 7884703 TI - Homelessness and ill health. Summary of a report of a working party of the Royal College of Physicians. PMID- 7884704 TI - The blood-brain barrier: clinical implications for drug delivery to the brain. AB - The blood-brain barrier (BBB) determines whether or not a given drug can reach the central nervous system (CNS), either by passive diffusion or through carrier or receptor systems. Initial work focused on the structural and physico-chemical requirements favouring transport across the BBB as related to anatomical and physiological features. Such studies have had a significant effect on the design of CNS-active drugs with improved permeability across the BBB. Progress in pharmacology and neurosciences resulted in greater knowledge of CNS diseases and of potential therapies, but also created the need to develop new strategies to improve drug delivery to the brain. For a long time the BBB was considered to be a physical barrier, mainly represented by the cerebrovascular endothelium; however, transport of drugs to the brain may be limited by the metabolic activity of the BBB. The BBB should be regarded as a dynamic rather than a rigid barrier; it can be influenced by astrocytes and probably also by neuronal and hormonal stimuli, and its properties are also affected by diseases of the CNS. This may offer new strategies for targeting drugs to the brain. PMID- 7884705 TI - Antisense DNA and RNA strategies: new approaches to therapy. AB - This review describes the results both in vitro and in vivo of the application of small DNA molecules or their analogues to target sequences in messenger RNA (mRNA) or DNA. Biological effects on the replication of viruses and the expression of oncogenes are recorded. At the same time, RNA catalytic sequences ('ribozymes') have been used to target and cleave mRNA sequences. Before these treatments can be confidently applied to clinical situations, further work is needed on their stability, cellular uptake and selection of their target, and the mechanism of their action also needs to be understood and controlled. In this way, it may be possible to guarantee specific effects on gene or cell type. The review describes the current research and state of development. PMID- 7884706 TI - Dissecting hypertension: the role of the 'new genetics'. AB - The tools of molecular genetics have recently been applied to hypertension, a common multifactorial disorder, with some success. Glucocorticoid-suppressible hyperaldosteronism, an inherited form of human hypertension due to the dominant inheritance of a chimaeric steroid 11 beta-hydroxylase/aldosterone synthase gene, has given an insight into the possible genetic factors involved in essential hypertension. Study of the aldosterone synthase and steroid 11 beta-hydroxylase genes has shown the presence of polymorphisms in both of these genes in human subjects; further studies may demonstrate genetic mutations with pathophysiological effects in patients with essential hypertension. PMID- 7884707 TI - Coordinating locally 'owned' treatment guidelines. AB - South West Thames Regional Health Authority established and commissioned a regional guidelines unit to coordinate the introduction of a set of treatment guidelines on the management of common medical emergencies into all the acute intaking National Health Service (NHS) hospitals throughout the region. All hospitals were offered a set of template guidelines to be used at their discretion for producing their own customised equivalent. They were also offered full typing and production facilities, together with printing costs if publication was achieved by a target deadline (1 August 1993). In 11 of the 14 NHS hospitals guidelines were available to hospital staff by the target deadline, and one set was produced for a non-NHS hospital. In two hospitals the target date was not met, and one other declined to take part. As part of the project the unit assessed the extent to which the published guidelines were adapted to meet the requirements of each individual hospital. The template offered guidelines on 34 topic titles. No hospital used all core titles of the original template; titles were omitted or replaced in some, and added in others. Where the original guideline titles were used, there was almost always some customisation--changes in sentence structure, names or contact numbers, alterations in drugs and doses or the addition or omission of entire sections. By using an established resource, sets of customised, locally determined treatment guidelines were introduced with relative ease into most of the acute hospitals in a UK health region. PMID- 7884708 TI - What the SHO saw. AB - As discussions about junior doctors' training and duty hours continue, we have looked at the actual 'on take' case load and case mix of a medical senior house officer (SHO) in a district general hospital (DGH) over a six-month period. In our DGH, on a one in four rota, exposure to a few common conditions is high and exceeds the minimum requirements for a post to be approved for general professional training. Limited but useful experience may also be gained in the management of many other conditions. The benefits in terms of structured training and lifestyle resulting from the implementation of the Calman report and the junior doctors' hours initiative need to be set against a possible reduction in patient exposure and in the associated opportunities to learn that may occur with a decrease in SHOs' 'front line' exposure. PMID- 7884710 TI - The marvel of the lung and human responsibility--'a great contempt of God's good gifts'? The Harveian Oration of 1994. PMID- 7884709 TI - The MRCP (UK) examination from the patient's point of view. AB - Each year approximately 3,200 volunteer patients attend the examinations of the Royal College of Physicians in England and Wales. A confidential postal questionnaire concerning patients' experiences and satisfaction was administered to those attending North Tees General Hospital in June 1992 with a 90% response rate. The majority of patients derive some enjoyment from the experience and do not mind being repeatedly examined, some even up to eight times per session; but they do feel neglected if examined only once per session. Twenty-two per cent of first time attenders would have liked to have had more information about the proceedings beforehand. PMID- 7884711 TI - Doctors in crisis: creating a strategy for mental health in health care work. PMID- 7884712 TI - The social and scientific value of biomedical research. PMID- 7884713 TI - Maternal and fetal origins of coronary heart disease. PMID- 7884714 TI - New directions in acute liver failure. PMID- 7884715 TI - Wheeze, sneeze and genes. PMID- 7884716 TI - MD candidates want better training in research. AB - A survey of MD candidates in one teaching hospital and two postgraduate institutes was undertaken to determine their initial training needs, and their preferred methods of learning about the conduct of research. Fifty-six respondents (53% response rate) replied to a piloted questionnaire. Their replies indicated a need for intensive initial research training, offered at local level by the supervisor. The supervisor's subsequent role throughout the research period should be to provide ongoing specific critical help and support. It is concluded that teaching materials and designed teaching sessions might be provided for supervisors to assist them in their new role. PMID- 7884717 TI - The Commonwealth doctor of medicine: a degree of uncertainty. AB - The degree of doctor of medicine (MD) is awarded by many universities in the British Commonwealth as a senior, postgraduate, research thesis-based degree. Some of its features are that it is limited to medical graduates of the same university, but that the research on which the thesis is based need not be conducted at the university awarding the degree and that there is no requirement for formal supervision of candidates. These characteristics, and its close similarities with the master of surgery (ChM) degree, may be responsible for the confusion that exists about its quality and status in relation to the doctorate of philosophy (PhD) and the 'higher' doctorates like doctor of science (DSc). There is also uncertainty about its role in the training and selection of clinical consultants and physician scientists. PMID- 7884718 TI - Myocardial infarction. AB - A conference on myocardial infarction (MI) was held at the Royal College of Physicians on 6 June 1994, organised by Dr K S Channer. The management of myocardial infarction has changed dramatically in the last few years with the introduction of effective measures to reduce early mortality and improve longterm prognosis. The purpose of this conference was to review these approaches and determine how they may be introduced into practice. The conference was divided into three sections: preventing myocardial infarction, acute intervention at the time of infarction, and preventing reinfarction. PMID- 7884719 TI - From medical apartheid to siyazamile in the Eastern Cape province. A medical student's elective period in South Africa. PMID- 7884720 TI - Gag and stroke. PMID- 7884721 TI - Work experience for sixth form students. PMID- 7884722 TI - Management of myocardial infarction. PMID- 7884723 TI - Management of myocardial infarction. PMID- 7884724 TI - Fanconi syndrome in a Labrador retriever. AB - A 2-year-old male Labrador Retriever was presented to the University of Missouri Veterinary Teaching Hospital with the primary complaints of polydipsia, polyuria, and joint or muscle pain. Low blood urea nitrogen concentration, hyperchloremia, and marked proteinuria were the only abnormalities in a serum biochemical profile and urinalysis. Decreased creatinine clearance and increased renal fractional excretion of sodium, potassium, calcium, and phosphorus were detected by renal clearance studies. Increased excretion of most amino acids was found by amino acid analysis of urine, but not all amino acids were lost with equal magnitude. Amino acids with secondary amino groups or basic side chains were lost at increased rates, whereas those with acidic side chains were not. These differences could be related to defects in specific renal amino acid transport mechanisms. Identification of these transport mechanisms may allow for pharmacologic intervention at the point of renal loss to alleviate clinical signs of disease. PMID- 7884725 TI - Thrombocytopenia associated with neoplasia in dogs. AB - Ten percent (214/2,059) of all dogs with cancer at North Carolina State University Veterinary Teaching Hospital had thrombocytopenia. The thrombocytopenia was associated with infectious/inflammatory etiologies in 4%, miscellaneous disorders (therapy, bone marrow failure, disseminated intravascular coagulation) in 35%, and neoplasia without identifiable secondary factors in 61% of cancer-bearing dogs. Classifying these dogs by tumor groups revealed the following proportionate ratios: lymphoid, 29%; carcinoma, 28%; sarcoma, 20%; hemic neoplasia, 7%; multiple, 5%; unclassified, 3%; benign, 3%; brain, 3%; and endocrine, 3%. Dogs with hemangiosarcoma, lymphoma, and melanoma were at increased risk of developing thrombocytopenia. Cytotoxic therapy was the major factor increasing the risk of thrombocytopenia in dogs with melanoma. Golden Retrievers were the only breed recognized with a predisposition to develop thrombocytopenia. If thrombocytopenia is identified in a dog with cancer, we recommend thorough evaluation of the coagulation system before surgery or therapy, and careful consideration of the risks and potential benefits of myelosuppressive or L-asparaginase therapy. PMID- 7884726 TI - Response of canine mast cell tumors to treatment with oral prednisone. AB - Twenty-five dogs with naturally occurring mast cell tumors were treated with daily oral prednisone (1 mg/kg) for 28 days. Five dogs (20%) had reduction in tumor volume and were considered responders. Four of these underwent partial remission and one underwent complete remission. Survival times for the five responders were 3, 5, 6, 7.5, and greater than 28 months, respectively. We therefore conclude that prednisone is effective in some canine mast cell tumors. Further studies are indicated to determine the most effective dose of prednisone, the appropriate duration of treatment, and the efficacy in more benign mast cell tumors, and in combination with other forms of therapy. PMID- 7884727 TI - Itraconazole for the treatment of histoplasmosis in cats. AB - Eight cats with histoplasmosis were treated with itraconazole at 5 mg/kg per dose PO bid. There were multiple sites of infection, and 2 of the cats had hypercalcemia that was attributed to the histoplasmosis. All 8 cats were eventually cured, but 2 cats experienced recurrences of disease after completion of therapy, requiring 2 to 3 additional months of itraconazole. There were no clinically relevant adverse effects during treatment. Although a limited number of cats were treated, the study suggests that itraconazole is a well-tolerated and effective drug for the treatment of histoplasmosis in the cat. PMID- 7884728 TI - Development of gastroscopic food sensitivity testing in dogs. AB - The aims of this study were to develop a gastroscopic food sensitivity testing (GFST) technique for clinical use in dogs and to determine if the results of GFST were influenced by the feeding of a hypoallergenic diet immediately before the testing period ("unmasking"). The technical requirements for GFST were devised during a total of eight endoscopies performed in four healthy dogs. GFST was performed in anesthetized dogs in sternal recumbency. Food extracts were dripped onto the dependent aspect of the body of the stomach via plastic tubing passed through the endoscope. Changes were observed within 2 to 3 minutes of application, and included localized mucosal swelling and erythema, generalized mucosal erythema, and hyperperistalsis. The influence of "unmasking" was then examined in 6 atopic and 2 healthy dogs, which underwent GFST on three occasions, 4 weeks apart. Before the first and third testing periods, the dogs consumed a commercial dry dog food. For 5 days before the second testing period the dogs were fed a hypoallergenic elemental diet. Oral challenges were performed to identify which of the dogs had clinically overt immediate food sensitivity. Localized swelling was most frequently correlated with positive challenge PO. No positive reactions occurred in response to the negative control extract (lamb). The number of positive GFST results increased after feeding the hypoallergenic diet. In conclusion, these preliminary results indicate that GFST holds substantial promise for the diagnosis of immediate food sensitivities affecting the gastrointestinal tract. The sensitivity of the procedure appears to be enhanced by preceding testing with a hypoallergenic diet. PMID- 7884729 TI - The natural clinical history of canine congenital subaortic stenosis. AB - The demographics and natural clinical history of canine congenital subaortic stenosis (SAS) were evaluated by retrospective analysis of 195 confirmed cases (1967 to 1991), 96 of which were untreated and available for follow-up evaluation. Of these, 58 dogs had left ventricular outflow systolic pressure gradients available for assessment of severity. All 195 dogs were used for demographic analysis. Breeds found to be at increased relative risk included the Newfoundland (odds ratio, 88.1; P < .001), Rottweiler (odds ratio, 19.3; P < .001), Boxer (odds ratio, 8.6; P < .001), and Golden Retriever (odds ratio, 5.5; P < .001). Dogs with mild gradients (16 to 35 mm Hg) and those that developed infective endocarditis or left heart failure were diagnosed at older ages than those with moderate (36 to 80 mm Hg) and severe (> 80 mm Hg) gradients. Of 96 untreated dogs, 32 (33.3%) had signs of illness varying from fatigue to syncope; 11 dogs (11.3%) developed infective endocarditis or left heart failure. Exercise intolerance or fatigue was reported in 22 dogs, syncope in 11 dogs, and respiratory signs (cough, dyspnea, tachypnea) in 9 dogs. In addition, 21 dogs (21.9%) died suddenly. Sudden death occurred mainly in the first 3 years of life, primarily but not exclusively, in dogs with severe obstructions (gradient, > 80 mm Hg; odds ratio, 16.0; P < .001). Infective endocarditis (6.3%) and left heart failure (7.3%) tended to occur later in life and in dogs with mild to moderate obstructions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884730 TI - Serum bile acid concentrations in dairy cattle with hepatic lipidosis. AB - This study was designed to evaluate serum bile acid measurements as indicatory, of liver function and/or hepatic fat infiltration in dairy cattle. Serum bile acid concentrations were measured in healthy dairy cattle at different stages of lactation after fasting or feeding. Bile acid concentrations were compared with liver fat content and sulfobromophthalein (BSP) half-life (T 1/2). Serum bile acid concentrations were higher in cows in early lactation and with higher daily milk production. Compared with prefasting values, bile acid concentrations were decreased at 8, 14, and 24 hours of fasting. Blood samples from fed cows at 1- to 2-hour intervals had wide and inconsistent variations in bile acid concentration. Because serum bile acids correlated well with BSP T 1/2, it is suggested that both measurements evaluate a similar aspect of liver function. Neither bile acids nor BSP T 1/2 correlated with differences in liver fat content among cows. Because of large variability in serum bile acid concentrations in fed cows and the lack of correlation of measured values with liver fat content, bile acid determinations do not appear useful for showing changes in hepatic function in fed cows with subclinical hepatic lipidosis nor serve as a screening test for this condition. PMID- 7884731 TI - Torsades de pointes-like polymorphic ventricular tachycardia in a dog. PMID- 7884732 TI - Acute intraoperative arterial elongation: histologic, morphologic, and vascular reactivity studies. AB - This study focuses on the histomorphologic damage produced by an acute elongation process, as well as on quantifying the alterations in arterial contractility following the application of this technique. Light microscopy and scanning electron microscopy studies were prepared from expanded and non-expanded pig superficial femoral arteries (SFA) harvested immediately following expansion, and again at 24- and 72-hr intervals. Histologically, the expanded vessels showed minor, patchy, endothelial slough, but not fragmentation of the internal or external elastic lamina. At 24 hr, the endothelium showed reactive changes, but no evidence of smooth-muscle necrosis of the tunica media was observed. At 72 hr, healing of the endothelium was evident by SEM. Similar specimens, also from the SFA, were harvested and placed in organ chambers immediately following expansion and 24 hr later, to measure contractility when exposed to alpha-adrenergic agonists. The vessels were exposed to the contractile agonists, phenylephrine and 5-hydroxytryptamine, which evoked similar concentration-dependent increases in tension in both the expanded group and the controls. From these observations, the authors conclude that acute intraoperative elongation of arteries results in only minor endothelial damage, without affecting the inherent contractility of the vessel wall. PMID- 7884733 TI - Morbidity associated with free-tissue transfer after radiotherapy and chemotherapy in elderly cancer patients. AB - Because of their ages and associated medical problems, many elderly cancer patients are treated with radiotherapy and/or chemotherapy to avoid the increased morbidity perceived to occur with prolonged surgical procedures such as tumor resection and reconstruction with free tissue transfer (FTT). The failure of such therapy still often requires tumor resection and reconstruction in irradiated tissue, which may add to the morbidity of surgery. To determine the validity of these concerns, 66 elderly cancer patients who underwent tumor resection and FTT after previous radiotherapy and/or chemotherapy (PT) were compared to a similar group of 64 elderly patients who had not received such previous therapy (NPT). Despite the two groups having similar patient traits, reconstructive-site characteristics, types of flaps used, medical risk factors, and time variables, there were no statistically significant differences between groups for FTT failure (PT3 percent, NPT 6 percent), medical complication rate (PT 16 percent, NPT 27 percent), surgical complication rate (PT 41 percent, NPT 49 percent), or wound-healing problems. The perioperative mortality rate was 2 percent. The authors conclude, that when medical problems are appropriately corrected before surgery, FTT may be safely performed in elderly patients with a high degree of success, acceptable morbidity, and low mortality. Previous cancer treatment does not appear to predispose elderly patients to a higher rate of FTT failure or wound-healing problems after FTT reconstruction. PMID- 7884734 TI - Effectiveness of a new non-thrombogenic bio-adhesive in microvascular anastomoses. AB - Negatively-charged fibrin glue was successfully prepared by combining human cryoprecipitate with succinic anhydride. The resulting bio-adhesive was tested for thrombogenicity and tensile strength by applying it to three groups of Sprague-Dawley rat femoral-artery anastomoses (6 suture, 2 suture, and no suture anastomoses). Anastomoses were tested by a standard patency test over 7 days. Both the 6-suture and 2-suture anastomoses with negatively-charged fibrin glue had 100 percent patency rates and no pseudoaneurysm formation over 7 days. When positively-charged fibrin glue was applied to sutured anastomoses, patency rates decreased gradually to 50 percent over 7 days. Fibrin glue alone (whether negatively- or positively-charged) does not have the tensile strength to maintain an anastomosis without sutures. However when applied to a two-suture anastomosis, the breaking strength of the anastomosis is more enhanced by the negatively charged fibrin glue. PMID- 7884735 TI - Diphallus in an adult: microsurgical treatment--case report. AB - A case of true, complete diphallus in an adult, associated with multiple malformations, is presented. The left urethra was perineal hypospadic; the right posterior urethra was small in caliber; and the right testis and spermatic cord were absent. The chordee was released; the right penis was resected and transferred to elongate the left one; and the urethra was reconstructed with a radial forearm free flap. Follow-up of more than 6 years shows that the patient has a good functional and cosmetic result. PMID- 7884736 TI - The fate of free, pedicled and free vascularized cancellous iliac bone grafts and the effect on the healing of femoral osteotomy: an experimental study. AB - A new model for vascularized and nonvascularized iliac bone autograft transfer to a femoral shaft osteotomy site is presented in this experimental study. As demonstrated on roentgenograms taken at 4 to 6 weeks postoperatively, callus formation between vascularized grafts and recipient sites was 1.5 to 2 times faster than in the nonvascularized graft transfer. According to densitometric analysis, conventional free grafts lost more hydroxyapatite and restored their mineral structure at a slower rate than vascularized grafts. There was no difference between free vascularized and pedicled grafts in the rate of mineral deposition changes, but the pedicle grafts had more significant loss of bone density. Formation and mineralization of periosteal callus between the femoral shaft fragments took place more rapidly in the first 12 weeks after pedicled bone transplantation. The correlation between the densitometric results and morphologic behavior of transplanted bones was examined. It was demonstrated that all of the grafts at the recipient site underwent remodeling into cortical bone. However, vascularized, and especially pedicled, grafts maintained their cancellous structure relatively longer. PMID- 7884737 TI - The radial forearm flap: a reconstructive chameleon. J Reconstr Microsurg 10(5):299-304, 1994. PMID- 7884738 TI - Endothelin: an endothelium-derived vasoactive peptide. AB - Endothelin is a 21-amino-acid, vasoactive peptide. Sequence analysis of cloned cDNAs for porcine and human endothelin precursors showed that endothelin-1 (ET-1) is produced in the endothelial cells. The peptide, endothelin (ET), was first identified as a potent vasoconstrictor. It is one of the most potent endogenous vascular smooth-muscle constrictors, ten times more potent than angiotensin II, vasopressin, and neuropeptide Y. Shortly after the discovery of this vasoconstrictor peptide, it was revealed that endothelin also possesses vasodilator properties at doses lower than those necessary to produce vasoconstriction. However, controversy still exists over the mechanism(s) of action; prostacyclin and endothelium-derived relaxing factor (EDRF) have mainly been implicated as the source of the initial vasodepressor effect. ET also elicits markedly different regional hemodynamic response patterns. There is a heterogeneity in the observed vasodilation or vasoconstriction, depending on species and on vascular beds studied in the same species. Endothelin has been implicated in a number of pathologic situations, including tissue ischemia and vasospasm. ET seems to be produced more actively around the site of endothelial damage; the loss of balance between its vasodilator- and vasoconstrictor-induced responses could contribute to its patho-physiologic properties. Experimental results strongly support the concept that ET could be important in controlling vascular tonus, both in the healthy and the diseased vessel. PMID- 7884739 TI - Application of the 3M microvascular anastomotic device in non-vascular tubular structures. PMID- 7884740 TI - Antibodies to sperm-specific human FA-1 inhibit in vitro fertilization in rhesus monkeys: development of a simian model for testing of anti-FA-1 contraceptive vaccine. AB - The feasibility of using the rhesus monkey as a non-human primate model for testing the efficacy of a contraceptive vaccine based on FA-1 antigen was evaluated. Affinity-purified anti-FA-1 polyclonal antibodies (Fab' fragments) and anti-FA-1 monoclonal antibody were used as probes in these studies. Anti-FA-1 antibodies (polyclonal Fab' as well as monoclonal IgG) predominantly reacted with the postacrosomal, mid-piece and tail regions of rhesus monkey sperm, as with human sperm, by an indirect immunofluorescence technique (IFT). These antibodies also specifically recognized a single protein band of 51 +/- 2 kDa, corresponding to the dimeric form of FA-1 antigen, on a Western blot of lithium diiodosalicylate (LIS)-solubilized monkey sperm. Anti-FA-1 antibodies, when present in the insemination mixture, inhibited the in vitro fertilization (IVF) of monkey oocytes. These results indicate that FA-1 antigen in rhesus monkey sperm is similar in subcellular localization, molecular identity and function to that in human sperm, and that the rhesus monkey represents a permissible non human primate model in which the efficacy of a contraceptive vaccine based on FA 1 antigen can be tested. PMID- 7884741 TI - The effect of human anticardiolipin antibodies on murine pregnancy. AB - Anticardiolipin antibodies (aCL) were affinity purified or isolated in the IgG fraction of serum from 6 patients with antiphospholipid antibody syndrome. Anticardiolipin antibodies from one patient consistently compromised murine pregnancy. However in 92% (45 of 49) of cases injection of human anticardiolipin antibodies had no adverse effect on murine pregnancy, regardless of whether affinity purified aCL or IgG fractions were used. It is concluded that in most cases human anticardiolipin antibodies alone do not induce murine fetal loss. PMID- 7884742 TI - Temporal recognition of sperm autoantigens by IgM and IgG autoantibodies after vasectomy and vasovasostomy. AB - Temporal patterns of IgM and IgG autoantibodies to sperm proteins were studied by western blot analysis at intervals after bilateral vasectomy, vasectomy followed one month later by vasovasostomy, or sham operations. Responses were detected to eight major autoantigens at 21-23, 36, 41, 51, 57, 63, 68-71 and 75-83 kDa, by study of staining patterns of sequential serum samples from individual animals and by analysis of the incidence of reaction to each protein. The four lower molecular weight antigens (21-23, 36, 41 and 51 kDa) provoked mainly IgG responses. The strongly stained set of higher molecular weight antigens (57, 63, 68-71 and 75-83 kDa) tended to show more clearly defined temporal patterns of IgM followed by IgG response, including a high incidence of IgM antibody at the 2 week interval. Three of the larger peptides (57, 63 and 68-71 kDa) appeared highly immunogenic, since some reactions were detected even in sham-operated rats. The classical patterns of IgM and IgG antibody responses to the majority of the dominant sperm autoantigens are in accord with the hypothesis that vasectomy mimics immunization with spermatozoa. The high incidence of IgM antibodies in the earliest sample, taken 2 weeks after vasectomy, suggests that the initial immunizing event takes place within about a week after the operation. Vasovasostomy did not bring about a decrease in antisperm antibodies. Instead, some animals demonstrated an increased reaction to certain antigens after reversal of vasectomy, even though the vasovasostomies were anatomically successful. PMID- 7884743 TI - Chemotaxis of polymorphonuclear leukocytes towards human pre-ovulatory follicular fluid and serum using a 'sparse-pore' polycarbonate filtration membrane. AB - The chemotactic responses of polymorphonuclear leukocytes (PMN) towards pre ovulatory follicular fluid and serum from patients participating in an in vitro fertilization program were tested in a modified Boyden chamber using a 'sparse pore' polycarbonate filtration membrane method. The chemotactic activities of follicular fluids were generally low, but were significantly higher in conceptual cycles than in non-conceptual cycles. The chemotactic activities of sera were generally high, but were significantly lower in conceptual cycles. The chemotactic activity of few follicular fluids ever exceeded that of serum, regardless of the occurrence of conception. These findings demonstrate for the first time using an appropriate technique, that pre-ovulatory follicular fluids can be chemotactic for PMN, but the relationship between this activity, serum chemotactic activity and successful pregnancy is not clear. PMID- 7884744 TI - Granulated metrial gland cells: hypotheses concerning possible functions during murine gestation. AB - Granulated metrial gland (GMG) cells are morphologically distinctive lymphoid cells found in the murine uterus only during gestation. The life history of GMG cells suggests that they have important roles during mammalian gestation but these roles have been difficult to define. Genetic and immunologic data suggest that GMG cells may be a specialized subset of natural killer (NK) lymphocytes. This has directed research on GMG cell functions towards questions of effector cell-target cell interactions. A broader range of potential functions is discussed and shifts in functional roles played by GMG cells are proposed over the course of gestation. PMID- 7884745 TI - Immunogenetic and serological investigations in nonpregnant and in pregnant women with a history of recurrent spontaneous abortions. German RSA/IVIG Study Group. AB - In the context of a controlled multicenter study on intravenous immunoglobulin (IVIG) treatment of patients with a history of unexplained recurrent spontaneous abortions (RSA), a number of controversial immunological parameters were evaluated prior to and during pregnancy with respect to their diagnostic and/or prognostic significance. A total of 390 serum samples from 52 patients were investigated. Sharing of 2 or more HLA (A, B, DR, DQ) antigens was significantly more frequent in RSA couples than in controls. The rate of cytotoxic or Fc receptor (FcR)-blocking antibodies was not significantly lower in RSA patients than in individuals with normal pregnancies. Both tumor necrosis factor-alpha (TNF-alpha) levels and IgG anticardiolipin antibodies (IgG-ACA) were significantly increased in the patient group. While the occurrence of HLA sharing, cytotoxic/FcR-blocking antibodies and IgG-ACA did not correlate with the outcome of pregnancy, TNF-alpha levels were found to be significantly higher in patients with subsequent miscarriage than in those with successful pregnancy. IgG ACA, if present, significantly decreased during the course of successful pregnancy but remained high in patients with subsequent abortion. It is concluded that the diagnostic and/or prognostic value of HLA sharing and cytotoxic/FcR blocking antibodies has been overestimated while TNF-alpha and ACA levels are potential diagnostic markers and/or exhibit prognostic significance in subgroups of RSA patients. PMID- 7884746 TI - Long-term intravaginal presence of foreign bodies in children. A preliminary study. AB - The similar clinical features of childhood sexual abuse, isolated premature menarche and intravaginal foreign objects prompted a preliminary study of the anatomic features of intravaginal foreign objects in premenarchal females. PMID- 7884747 TI - Vulvar vestibulitis. Lack of evidence for a human papillomavirus etiology. AB - Prompted by contradictory papers on the subject, we performed a prospective study to assess the possible human papillomavirus (HPV) etiology of vulvar vestibulitis. Eleven patients with periglandular vestibulitis, as well as a control group of 11 patients with condylomata acuminata, were selected. Biopsy specimens were taken for histologic and virologic evaluation. One specimen of vestibulitis showed koilocytosis. Using the polymerase chain reaction, none of the vestibulitis specimens, including the one with koilocytosis, were found to harbor HPV DNA, whereas all the condylomata acuminata contained HPV 6/11 DNA. Our results do not support an HPV etiology of vestibulitis. PMID- 7884748 TI - Plasma cell balanitis and vulvitis (of Zoon). A study of 10 cases. AB - We report six cases of plasma cell balanitis and four of plasma cell vulvitis. The patients' ages ranged from 26-88 years in males and 30-60 in females. All the men were uncircumcised and presented with a discharge and erythematous lesions on the glans penis and prepuce. In females the main presenting complaints were vulvar soreness, pruritus, smarting/burning, discharge and bleeding. Two were on hormone replacement therapy, two had undergone a mastectomy for carcinoma of the breast, and one was an insulin-dependent diabetic. Another patient subsequently developed diabetes mellitus. Topical and intralesional corticosteroid preparations resulted in satisfactory improvements in all cases, male and female. Two males subsequently underwent circumcision, which was curative. PMID- 7884749 TI - Vulvar and vaginal melanoma. A clinicopathologic study. AB - Melanoma of the vulva is uncommon, and melanoma of the vagina is rare. The overall prognosis is poor and worse than for cutaneous melanomas. This appears to relate to diagnosis of genital lesions at an advanced stage. In a 28-year, retrospective analysis at Columbia Presbyterian Medical Center, there were 10 cases of primary melanoma of the lower genital tract. Seven cases of vulvar melanoma and three cases of vaginal melanoma were reviewed. All cases were in elderly women, and all were diagnosed at an advanced stage. The outcome in general was poor, regardless of therapy. This condition must be recognized earlier to afford an optimal patient outcome. Elderly women must undergo regular gynecologic care, and suspicious pigmented lesions must be biopsied. PMID- 7884750 TI - Membranous hypertrophy of the posterior fourchette as a cause of dyspareunia and vulvodynia. AB - Twenty-one women were treated surgically for entry dyspareunia and vulvodynia. The ages of the patients ranged from 18 to 39 years (mean, 24.5). Physical examination showed the presence of membranous hypertrophy of the posterior fourchette with consequent stricture of the vaginal introitus in all the patients. Eighty percent of the patients had erythema and tenderness of the vestibule, particularly in the posterior part. The histologic findings were somewhat enigmatic and quite unimpressive, frequently suggestive of chronic nonspecific inflammation; in only two cases were histologic changes suggestive of human papillomavirus infection observed. All the patients underwent excision of the posterior part of the vestibule with vaginal advancement under general anesthesia. Follow-up showed elimination of the symptoms in 19 patients and an improvement in the symptoms in the remaining 2. PMID- 7884751 TI - Assessing vulvar lesions. Laser-Doppler flowmetry as a possible technique. AB - Over the last decade, laser-Doppler flowmetry has been used to measure perfusion in the skin. To date it has not been used on the lower genital tract, and we describe preliminary results of measurements taken on the vulva. We include results from a control population and describe two cases with premalignant or malignant changes in the vulva. PMID- 7884752 TI - Syringoma of the vulva. A case report. AB - Syringoma of the vulva, especially as the multiple form, is a rare disorder. A review of the diagnoses in 4,500 patients from the Vulvar Clinic, Hospital de Clinicas Jose de San Martin, First Chair of Gynecology, Buenos Aires University, revealed only three cases, two of which were asymptomatic. The third patient, with multiple lesions and severe discomfort, is presented. With cryotherapy the lesions healed, and the patient was asymptomatic even during warm weather. PMID- 7884753 TI - Psychological distress in women with nonneoplastic epithelial disorders of the vulva. AB - The aim of this study was to evaluate psychological distress in 44 women with vulvar squamous cell hyperplasia and 21 with vulvar lichen sclerosus in order to examine the presence of psychological factors in these dermatologic disorders. Two psychometric tests were used to evaluate depressive status and various aspects of anger. No significant depressive status was diagnosed with the former test either in patients with vulvar squamous cell hyperplasia or in patients with vulvar lichen sclerosus. Patients with squamous cell hyperplasia had two components of anger (state and internal anger) that were significantly higher and three components (trait anger, exteriorization and control of anger) significantly lower than did the controls. In patients with lichen sclerosus all the components of anger were within the normal range. These findings suggest that psychological factors may be associated with vulvar conditions, such as squamous cell hyperplasia, and may have some therapeutic implications in cases resistant to standard treatment. PMID- 7884754 TI - Preoperative serum CA-125 and CA-72 in predicting endometriosis in infertility patients. AB - CA-125, a high-molecular-weight glycoprotein antigen, has been identified as a possible marker for endometriosis, with discrepant results. CA-72, another glycoprotein antigen, is expressed by a variety of adenocarcinomas, including endometrial carcinoma. This controlled, prospective study evaluated serum CA-125 and CA-72 levels in 35 consecutive patients with endometriosis of varying stages and in patients without endometriosis. Serum CA-125 and CA-72 were measured with immunoradiologic methods prior to diagnostic laparoscopy for infertility evaluation. Endometriosis, scored by American Fertility Society guidelines, was identified in 19 patients, and 16 patients had normal pelvic findings. CA-125 and CA-72 levels were not different between patients with no pelvic disease (controls) and women with stage I-IV endometriosis. The positive predictive value of CA-125 was 0%; the negative predictive value was 47%. The positive predictive value of CA-72 was 5%; the negative predictive value was 53%. CA-72 and CA-125 are not helpful in the routine workup of the infertile woman to determine the likelihood that she has pelvic endometriosis. PMID- 7884755 TI - Ambulatory blood pressure monitoring during pregnancy with a new, small, easily concealed monitor. AB - Before establishing the utility of ambulatory blood pressure monitoring during pregnancy, we evaluated the accuracy of a small, easily concealed monitor. The 59 normotensive pregnant patients were between 13 and 26 gestational weeks. For each monitor reading, two trained observers independently and simultaneously recorded blood pressures using a mercury manometer connected to the monitor cuff. Seven readings in three positions (sitting upright, semirecumbent, standing) were performed on each patient. Averaged differences between the observers' and monitor readings varied from -2.2 to -0.9 mm Hg (systolic) and from -2.8 to -0.6 (fifth-phase diastolic), indicating slight but clinically unimportant overestimation by the monitor. Correlations between averaged observers' readings and the monitor ranged from 0.79 to 0.92 (systolic) and from 0.85 to 0.92 (fifth phase diastolic). Overall, the observers agreed with the monitor within 5 mm Hg on 94% of systolic readings and 99% of fifth-phase diastolic readings. There was no statistically significant difference in accuracy with changes in body position. We conclude that this small, quiet, noninvasive device accurately determined blood pressures during pregnancy. PMID- 7884756 TI - Abnormal cervical cytology in adolescents. A 15-year experience. AB - The onset of sexual activity at a young age (< 17 years) has been identified in several studies as the most important epidemiologic risk factor in the development of cervical intraepithelial neoplasia (CIN). In characterizing the natural history of CIN, investigators have indicated that a percentage of such lesions progress to invasive carcinoma if left untreated. CIN in adolescents was first reported in 1961. The subsequently reported CIN prevalence rates in sexually active, medically indigent teenage populations have increased over time, temporally paralleling increasing early sexual activity among teenagers. In our 15-year experience with abnormal cervical cytology in adolescents, all grades of CIN were observed. Fully 13% of patients had histologically proven CIN 3, a preinvasive lesion. Given reports of an increase in cervical cancer in young women (< 35 years old), the findings of this and similar studies mandate routine cervical cytologic screening in all sexually active teenage girls. PMID- 7884757 TI - Carbohydrate sources for gestational diabetes mellitus screening. A comparison. AB - One hundred eight patients were prospectively randomized to receive 50 g of a glucose polymer, d-glucose or a candy bar during a one-hour gestational diabetes mellitus (GDM) screening. The polymer had a mean serum glucose similar to that of d-glucose, with significantly fewer side effects, allowing an increased rate of examination completion. The candy bar produced a significantly lower mean serum glucose but had the highest rating for flavor. The polymer was an inexpensive and well-tolerated alternative for GDM screening, while the use of a candy bar needs more study. PMID- 7884758 TI - Giant mucinous ovarian tumor with low malignant potential with foci of well differentiated mucinous adenocarcinoma masked by massive obesity. A case report. AB - A giant (64-kg) mucinous tumor with low malignant potential and foci of well differentiated mucinous adenocarcinoma was removed from a massively obese (250 kg) woman. This case represents the largest tumor of this type reported to date. PMID- 7884759 TI - One laparoscopic puncture for treatment of ovarian cysts with adnexal torsion in early pregnancy. A report of two cases. AB - In two cases a simple laparoscopic technique was used to treat ovarian cysts with adnexal torsion in early pregnancy. A single laparoscopic route was sufficient. This procedure has great value for girls and young women for whom the preservation of fertility is a major concern. PMID- 7884760 TI - Preterm labor and congenital candidiasis. A case report. AB - Intrauterine infection with Candida is a rare complication of pregnancy. We report a case of preterm labor associated with Candida chorioamnionitis and the subsequent delivery of an infant with congenital Candida infection. We also discuss possible factors responsible for the increased invasiveness of this usually benign condition and management considerations once the diagnosis is made. PMID- 7884761 TI - A review of the mechanisms of oral tolerance and immunotherapy. AB - The induction of oral tolerance by oral immunization has been well recognized. Accumulated evidence shows that oral tolerance can be mediated by orally activated humoral and cellular factors. In animal models, the development of several T cell-mediated autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, uveitis and diabetes type 1 can be inhibited by oral immunization of the respective antigens. In allergy, oral administration of certain allergens can prevent and reduce both contact and atopic dermatitis. Oral tolerance to alloantigen also reduces graft rejection. In spite of these encouraging results, the usefulness of this approach for an alternative immunotherapy in humans needs to be investigated further. PMID- 7884762 TI - Acts of commission, omission, and demission or pulling the plug. AB - The difference between withholding and withdrawing treatment and actively killing is analysed. The intention of the physician and the effect on the patient are similar but the wider effect on others is different. The harmful effects of withdrawing life-preserving treatment which is no longer beneficial can be reduced by clarification of its purpose. This is to prolong life with value to the patient not just existence. PMID- 7884763 TI - Pitfalls in the interpretation of studies: I. PMID- 7884764 TI - Accuracy of duplex versus angiography in patients undergoing carotid surgery. AB - The operative findings of 23 carotid arteries were compared with pre-operative duplex scans and angiography. Both duplex and angiography had a high degree of accuracy in detecting haemodynamically significant lesions of 50-99% (88 and 92%, respectively). Their accuracy, however, in correctly predicting the grade of stenosis was significantly lower; 30 and 48%, respectively (P < 0.001). They each exhibited an accuracy of 70% and 78%, respectively, in the detection of ulceration. Overall, both duplex and angiography displayed an accuracy of 87% in indicating the proper management course. The combination of both investigations increased this accuracy to 94.6%. In severely stenotic lesions, duplex to rule out occlusion was not reliable. On statistical analysis, there was no difference between duplex and angiography in predicting haemodynamically significant lesions of 50-99%, estimating the grade of stenosis, the detection of ulceration, or indicating the proper management course. In most situations, duplex alone equalled the accuracy of angiography in the pre-operative assessment of patients for carotid surgery. For stenotic lesions of > 90%, however, we recommend supplemental angiography to rule out occlusion. PMID- 7884765 TI - Causes of death in renal transplant recipients: a study of 102 autopsies from 1968 to 1991. AB - A study was conducted on 102 patients submitted to renal transplant who died and were autopsied at the University Hospital, Faculty of Medicine of Ribeirao Preto, Brazil, from 1968 to 1991. The cause of death, based on a review of medical records and autopsy reports, was assigned to one of the following categories: infectious (69.6%); cardiovascular (12.7%); gastrointestinal (7.8%); graft rejection (6.9%); tumoral (2.0%); and undetermined (1.0%). Among the 71 cases of death caused by infection, 28 (39.4%) showed disseminated agents involving two or more organs. Isolated pneumonia involved 17 patients (23.9%), followed by acute pyelonephritis in the transplanted kidney in 10 patients (14.1%). The most frequent agents were: bacteria (58.0%), divided into 'non-classified' (83.0%), Nocardia (10.6%) and Mycobacterium (6.4%); fungi (27.5%) represented by Cryptococcus (22.7%), Aspergillus, Candida and Pneumocystis carinii (18.1% each), Histoplasma (13.6%), Mucor and Paracoccidioides brasiliensis (4.5% each); viruses (6.2%) represented by Herpes simplex (60.0%); metazoa (5.0%, S. stercoralis), and protozoa (2.5%, T. cruzi). Cytomegalovirus (CMV) was identified in the lungs of 12 patients and was not directly correlated with death but was associated with other agents. In conclusion, immunodepressed patients such as renal transplant recipients should be carefully monitored for infection due to the high mortality rate. PMID- 7884766 TI - The importance of pubic pain following childbirth: a clinical and ultrasonographic study of diastasis of the pubic symphysis. AB - This study aimed to investigate the diagnosis and consequences of pubic symphysis diastasis postpartum, in particular the use of ultrasonography to measure interpubic gap. It was a prospective follow-up study, which included an ultrasonographic comparison between symptomatic mothers and controls, set in Morriston Hospital, Swansea. Nine women presenting with unusual pubic pain post partum were included: there were no exclusion criteria. Forty-two controls were also studied: the only exclusion criterion was unusual pubic pain. Interpubic gap was measured with ultrasonography. Follow up was undertaken for a median of 37 months (range 2-57). An abnormal interpubic gap was found in all symptomatic women. The incidence of diastasis was found to be at least one in 800 deliveries and significant long-term disability was found in three women. Diastasis is commoner than generally acknowledged and its consequences may be severe. Interpubic gap confirms diagnosis but does not appear to predict outcome. Ultrasonography aids diagnosis and follow up. PMID- 7884767 TI - Are ethical committees reliable? AB - This paper aims to assess the reliability of Local Research Ethical Committees (LREC), using a genuine research proposal which was sent to six LRECs. The main outcome criteria were modifications demanded by committees and the degree of agreement between them. All but one of the committees demanded some change in the proposal. None of the committees asked for the same changes. Our conclusion is that LRECs are highly variable. PMID- 7884770 TI - Wound drains in proximal femoral fracture surgery: a randomized prospective trial of 177 patients. AB - We report on the effect of wound drains on wound healing following surgery for proximal femoral fractures. One hundred and seventy-seven patients undergoing AO dynamic hip screw (DHS) or hemiarthroplasty were randomized whether or not to receive wound drainage. Patients who received wound drainage showed statistically better wound healing in terms of the ASEPSIS wound scoring system and a reduced infection rate. This study conflicts with previous smaller studies which failed to show an effect of wound drainage upon wound healing. PMID- 7884768 TI - The role of oncogenes and tumour-suppressor genes in the aetiology of oral, head and neck squamous cell carcinoma. PMID- 7884771 TI - Bascom's operation for pilonidal sinus. AB - During 1985 in England and Wales, 7000 patients were treated for pilonidal disease with an average hospital stay of 5 days. The aim of this paper is to report our early experience with Bascom's operation for pilonidal sinus--a procedure relatively untried in the UK. PMID- 7884772 TI - Intravascular stenting following bypass grafting in terminal coronary artery disease. AB - Reoperation after coronary artery bypass grafting in terminal coronary artery disease is associated with a substantial risk. Advances in coronary artery angioplasty offer alternative treatment with low morbidity and acceptable mortality. PMID- 7884773 TI - Amyloid tumour of the rectum. AB - Systemic amyloidosis results in diffuse deposition of amyloid proteins in various organs. Localized deposits in the form of nodules also occur but are rare in the gastrointestinal tract. A localized amyloid deposit in the rectum that was clinically indistinguishable from carcinoma of the rectum or prostate is described. PMID- 7884775 TI - False aneurysm of the carotid artery. AB - Vascular injury following penetrating neck trauma may be present despite a lack of clinical signs. Management of wounds deep to platysma should include a high level of suspicion and thorough investigation to exclude these 'silent' vascular injuries. This may prevent serious late complications. PMID- 7884774 TI - Cancer outlook: an African perspective. AB - In all western populations, mortality rates from cancer are high and even increasing: moreover, incidence rates of some cancers are also rising. As to propitiousness of preventive factors, genetic, gender, and age are beyond alteration: much the same applies to certain protective factors, e.g. late menarche, teenage pregnancy, high parity, long lactation, and greater physical activity. Influential dietary factors, i.e. intakes of energy, fat and fibre, often do not lend themselves to major alteration. Although reductions in smoking have occurred, the practice remains widespread and the intake of alcohol remains high. In developing countries, such as Africa, life-style changes are occurring and the population is incurring all risk factors mentioned. Whereas cancer is relatively uncommon in rural dwellers in developing countries, it is increasing in the huge peri-urban and urban populations due to changes in diet and way of life. Although knowledge should enable us to halve cancer's burden, hopes for meaningful changes are meagre. Survival time can be lengthened by more effective screening, especially of the very susceptible, and by further advances in treatment. Since known risk factors account for only half or less of occurrences of cancer, further rises, or, hopefully, welcome falls, could conceivably occur in the future. We must continue to try to educate the public regarding cancer avoidance: compliance by even a small proportion of those at risk could benefit huge numbers. PMID- 7884776 TI - Haemorheology--science and medicine. PMID- 7884777 TI - Anxiety and depression in migraine. PMID- 7884778 TI - Cigarette smoking in psychiatric inpatients. PMID- 7884779 TI - Glue ear. PMID- 7884780 TI - Measurement in normal aging. PMID- 7884781 TI - Ovarian remnant syndrome. PMID- 7884782 TI - Topical guanethidine relieves dental hypersensitivity and pain. PMID- 7884783 TI - Stephen Hales and the measurement of blood pressure. AB - Natural philosopher and inventor, Stephen Hales (1677-1761), undertook a lengthy series of experiments on animals described in Haemastaticks (1733) which led to the first direct measurement of blood pressure. Hales retained his interest in health and disease throughout his life, and this prompted what he regarded as his most important work: the invention of ventilation systems for use in ships or prisons. Hales was the 'perpetual curate' of Teddington, Middlesex, and he combined a mechanistic, quantitative approach to his experimental work with a need and, as he saw it, a duty to discover and wonder at the wisdom and goodness of God by studying His creation. PMID- 7884784 TI - Short-term (six hour), ambulatory blood pressure monitoring. AB - The feasibility of substituting a shorter duration of ambulatory blood pressure monitoring (ABPM) for 24h ambulatory monitoring to evaluate increased office BP measurements was investigated by analysing the records of 126 normal volunteers and 168 mildly hypertensive patients receiving placebo, including 22 studied on two occasions two months apart. The value to be predicted was the long-term awake BP mean for an individual (usual BP). Among the subjects studied on two occasions, there were no systematic differences between the two occasions and there was reasonable correspondence between the hourly patterns. Estimated variance components were substituted in a formula for the standard error of prediction (SEP) of the usual awake mean BP, for various durations and frequencies of monitoring. The lower limit of the SEP was determined by the patient-by-occasion component of variance. As few as six hours of monitoring with two to three readings/hour achieved most of the gain in precision obtainable by going from single BP readings toward continuous measurement during an entire awake period. In the remaining subjects, the influence of the day rhythm of BP on short-term monitoring was examined by measuring the differences in means of 6h periods from the full awake mean BP for starting times from 7 am to 3 pm. Among normotensives and hypertensive patients with near normal office BP (< 144/< 96 mmHg), there was little difference due to starting time. There was, however, a slight positive bias in the more hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884785 TI - Comparison of indirect and direct blood pressure measurements with Osler's manoeuvre in elderly hypertensive patients. AB - Indirect (cuff) and direct (intra-arterial) BPs were measured in 15 normotensive (mean age 79 years, range 72-88 years) and 21 hypertensive (mean age 76 years, range 65-89 years) elderly patients. Osler's test and arm arterial compliance, measured using Doppler-shifted ultrasound, were also assessed. In the normotensive, cuff systolic pressures were less than the direct by > 20 mmHg in 10 of the 15 (mean cuff systolic 139 +/- 13: direct 160 +/- 20 mmHg, P < 0.001); there was no statistical difference between the cuff and direct mean diastolic pressures (mean cuff diastolic 75 +/- 8; direct 70 +/- 10 mmHg). In the hypertensives, one had pseudohypertension (cuff systolic 186: direct 152 mmHg). However, cuff systolic pressures were less than the direct by > 20 mmHg in 11 (mean cuff systolic 205 +/- 26: direct 224 +/- 31 mmHg, P < 0.05); cuff diastolic pressures were greater than the direct by > 10 mmHg in 10 (mean cuff diastolic 102 +/- 14; direct 93 +/- 16 mmHg, P < 0.05). There was no significant difference between cuff and direct mean arterial pressures or the compliance in the normotensive and hypertensive groups. Osler's test was negative in the pseudohypertensive patient while in the four positive tests cuff systolic pressures were less than the direct measurements. In elderly patients there was no significant difference between the mean BP for cuff and direct measurements; systolic pseudohypotension and diastolic pseudohypertension are common and Osler's test is misleading. PMID- 7884786 TI - Increased blood pressure variability during 24h blood pressure monitoring as an early sign of autonomic dysfunction in non-insulin-dependent diabetics. AB - To evaluate the presence of early autonomic dysfunction in non-insulin-dependent diabetics we examined 24h control of blood pressure (1/4 hourly readings day and 1/2 hourly at night, using TM 2420) in 20 non-insulin-dependent diabetics, controlled only on diet or oral hypoglycaemics and 20 age/sex/BP matched non diabetics selected from a random population survey. The two groups were aged 52 +/- 9 years and 53 +/- 8 years, respectively. Both groups included normotensives and mild hypertensives in equal numbers but none was on antihypertensive treatment. The groups were well matched for daytime systolic blood pressure (SBP; 132.2 +/- 11.4 vs. 131.2 +/- 10.3) and diastolic blood pressure (DBP; 82.1 +/- 8.3 vs. 81.1 +/- 7.0). The diabetics had a significantly greater heart rate (HR) both during the day (79.6 +/- 9.5 vs. 72.3 +/- 8.8: P = 0.015) and during sleep (67.7 +/- 6.8 vs. 62.5 +/- 8.9). There was increased BP variability in the diabetics during the day (standard deviation of SBP; 16.9 +/- 6.2 vs. 13.3 +/- 4.7: P < 0.05) but the difference for DBP variability was not significant. The day-night difference for SBP, DBP, HR and HR variability was the same in both groups. We conclude that in these patients there was evidence for an alteration in BP variability (which may reflect baroreflex insensitivity) at a stage where there was no alteration in day-night rhythms of BP or HR. The increased HR both at day and night may also reflect baroreflex dysfunction and/or sympathovagal imbalance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884787 TI - Relationship of alcohol consumption and smoking to plasma cortisol and blood pressure. AB - The role of plasma cortisol in the relationship of alcohol consumption and smoking with BP was investigated in a study of 297 Japanese men, aged 50-54 years, who were not receiving antihypertensive agents. They were admitted to the Self-Defense Forces Fukuoka Hospital between January and June 1992 for a detailed pre-retirement health examination. A history of alcohol consumption and cigarette smoking were determined from a self-administered questionnaire. The plasma level of cortisol and BP were determined in the morning of the first admission day. While the plasma level of cortisol was positively related to systolic and diastolic BP, cortisol levels did not vary substantially with alcohol consumption. Both BP and plasma cortisol levels were lower among current smokers than nonsmokers. The lower BP observed among current smokers was ascribed in part (about 20-30%) to the plasma cortisol levels. While the cortisol levels may contribute the lower BP among current smokers, the data did not support its role in mediating the alcohol-BP relationship. PMID- 7884788 TI - Is there a role for dietary fish oil in the treatment of hypertension? AB - Hypertension and atherosclerosis are highly prevalent disorders which contribute substantially to the burden of premature morbidity and mortality at significant cost to the economy. Hypertension, abdominal obesity and risk factor clustering represent complex regulatory disorders which probably reflect an interaction of multiple genetic and environmental factors. Information has been summarised which indicates that fish oil, obtained either as a dietary supplement or by the consumption of more fish products, represents a relatively simple and comparatively inexpensive dietary intervention which may lower BP, especially in combination with a low salt diet, and favourably alter multiple risk factors in the cluster. This summary also indicates that multiple significant gaps in our knowledge about fish oil remain. Closing these gaps through further clinical and basic research may lead to greater acceptance and more appropriate therapeutic use of fish oil for health maintenance and disease prevention. PMID- 7884789 TI - Combined effect of a low fat diet and doxazosin on blood pressure control and blood lipids. Hunter Hypertension Research Group. AB - Doxazosin, a once daily alpha-blocking drug has been demonstrated to reduce both BP and hyperlipidaemia, related risk factors for premature vascular disease. This study was designed to see if a low fat diet altered the favourable effect of doxazosin on blood lipids in adults with mild to moderate hypertension and mild to moderate hypercholesterolaemia (5.6-8.0 mmol/l). Following a six week period on a low fat diet, patients were randomly allocated to additional doxazosin (2-8 mg/day) or enalapril (5-20 mg/day) treatment for a further 10 weeks. Forty-four of 55 subjects completed the study. A low fat diet reduced mean body weight by 2 kg without significantly altering blood lipids (total and HDL cholesterol, triglycerides). Doxazosin (4.5 +/- 2.9 mg/day) and enalapril (12.5 +/- 6.5 mg/day) produced a comparable lowering of sitting and standing BP at all visits and also produced similar 24h BP control. The expected increase in HDL cholesterol concentration previously noted in this patient population in association with doxazosin treatment was not detected suggesting that the low cholesterol-high carbohydrate diet, at least acutely, attenuates this potentially beneficial effect on plasma lipids. In summary, doxazosin has a comparable tolerability and BP lowering ability to enalapril. However, its ability to increase HDL cholesterol may be reduced in patients on low fat diets. PMID- 7884790 TI - One year experience of elderly hypertensive patients with isradipine therapy. AB - This is the first report of long-term use (one year) of isradipine, a new dihydropyridine calcium channel blocker, in the treatment of elderly patients with essential hypertension. Patients completing a three month, double-blind, multicentre study comparing isradipine to hydrochlorothiazide (HCTZ) were eligible to enroll in this open-label, continuation study. At initial baseline, patients were at least 60 years of age and had DBP from 95 mmHg to 120 mmHg. Patients were titrated when necessary every two weeks with isradipine, 5 mg to 15 mg once daily or 2.5 mg to 10 mg twice daily, to maintain sitting DBP < or = 90 mmHg. HCTZ, 12.5 mg to 50 mg once daily, could be added for better BP control. A total of 136 patients completed the one year, open-label phase. One hundred and fourteen patients (84%) received isradipine as monotherapy (mean dose, 9.7 mg/day); 22 received concomitant HCTZ therapy at one year. Reduction in DBP was significant and similar among all age groups and races (mean change of -19 mmHg). Reduction in SBP was similar among all age groups. Ninety-four per cent of those receiving isradipine monotherapy achieved BP control during the last four months of treatment. Twenty-six patients (16%) withdrew from the study: 11 (7%) had adverse reactions (one with headache, two with pedal oedema, eight with other problems); 11 (7%) had nondrug-related problems; and in four (2%), the drugs were ineffective. Based on these observations, isradipine is a well-tolerated, safe and effective agent for long-term BP control in elderly patients with essential hypertension. PMID- 7884791 TI - Long-term efficacy and safety of moexipril in the treatment of hypertension. AB - The purpose of this study was to assess the long-term efficacy and safety of moexipril, a new angiotensin-converting enzyme inhibitor, alone or in combination with hydrochlorothiazide in patients with hypertension. The patient population consisted of 281 hypertensive men and women, 30-84 years old, with seated diastolic BP between 95 and 114 mmHg. The study was a two year multicenter (22 centers), open-label protocol of moexipril monotherapy or combination therapy (with hydrochlorothiazide). Blood pressure, pulse rate, weight, adverse side effects and laboratory studies were assessed following moexipril dosing at 7.5, 15 or 30 mg once daily or 15-30 mg daily in combination with 12.5 mg hydrochlorothiazide if the DBP was > or = 90 mmHg. The primary measure of efficacy was change from baseline in seated DBP. Secondary outcome measures included changes in seated SBP, heart rate, laboratory parameters and subjective complaints. Following one year of therapy in 183 patients, the BP fell 13/14 mmHg among patients receiving moexipril monotherapy and 18/15 mmHg those receiving combined therapy compared with baseline (P < 0.001 for both). After two years of treatment, reductions were similar in 161 patients. Forty-four (16%) patients were prematurely withdrawn from the study because of inadequate therapeutic response and 34 (12%) secondary to adverse experiences. There were no changes in pulse rate or postural BP reductions. Four adverse side-effects occurred at a frequency exceeding 2% that were possibly or probably attributable to moexipril: fatigue (3%), headache (2%), dizziness (3%) and increased cough (5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884792 TI - Plasma renin activity, aldosterone and catecholamines in phaeochromocytoma: effect of converting enzyme inhibition. PMID- 7884793 TI - Hypertension and mortality in Antigua. PMID- 7884794 TI - Transmissible spongiform encephalopathies. PMID- 7884795 TI - Chronic bacteraemia due to Staphylococcus epidermidis after bone marrow transplantation. AB - A chronic bacteraemia due to Staphylococcus epidermidis occurred in a patient undergoing allogeneic bone marrow transplantation. Forty-two S. epidermidis isolates were obtained from blood cultures over a period of 5 months. Isolates were separated into three groups by SmaI macrorestriction characterisation with pulsed-field gel electrophoresis (PFE-1, one isolate; PFE-2, 32 isolates; PFE-3, nine isolates). Differences were detected in antimicrobial susceptibility patterns among isolates belonging to group PFE-2. The two strains, PFE-2 and PFE 3, were both responsible for the chronic bacteraemia and were isolated during different admissions to the hospital. A central venous catheter was the portal of entry for PFE-2. DNA macro-restriction analysis with pulsed-field gel electrophoresis was helpful in the epidemiological investigation of this S. epidermidis chronic bacteraemia. PMID- 7884796 TI - Comparison of streptococci of serological group B isolated from healthy carriers and active disease in Chile. AB - Serotyping of 50 streptococcal strains of serological group B isolated from human clinical specimens in Chile revealed mainly the serotypes Ia, II and III, either alone or in combination with protein antigens c or R. No significant difference in serotype distribution was detected between group B streptococci isolated from cervical swabs from clinically healthy women and those isolated from various pathological processes. Determination of antibiotic susceptibility of the bacteria demonstrated resistance to tetracycline and minocycline in 29 isolates. All 29 tetracycline-resistant cultures hybridised with a gene probe for tet(M). Again, no differences were detected between the group B streptococcal isolates of various origins. PMID- 7884797 TI - Possible virulence factors involved in bacteraemia caused by Aeromonas hydrophila. AB - Eighteen strains of Aeromonas hydrophila from patients with bacteraemia were investigated for possible virulence factors. Cytotoxin and haemolysin were produced by all strains, whereas cholera toxin-like factor was produced by 33% of strains only. Enterotoxin production was not detected. Haemagglutination of guinea-pig, fowl and rabbit erythrocytes was demonstrated by 83%, 67% and 61% of strains, respectively. Fucose- and mannose-sensitive haemagglutinins were predominant. None of the strains agglutinated sheep erythrocytes. Extrachromosomal DNA was detected in 17 strains, 16 of which had a plasmid (3.6 5.1 MDa), the majority being between 4.6 and 5.1 MDa. PMID- 7884798 TI - Detection of haemolytic activity of campylobacters by agarose haemolysis and microplate assay. AB - There are several methods for the detection of haemolytic activity in campylobacters. However, we found the haemolytic effect of campylobacters on conventional blood agar plates to be variable, inconsistent and difficult to interpret. Blood agarose plates showed campylobacter haemolytic activity more clearly. The incubation conditions (temperature and gaseous) appear to be important for the expression of this activity. Ninety four percent of the Campylobacter isolates examined were found to be haemolytic by the microplate assay with minimal haemolytic units that ranged from 1 to 64. Haemolytic activity was detected only from live bacterial cultures and not from any of the 50 bacterial culture supernates, which suggests that campylobacters may possess a cell-associated haemolysin. The identification of such haemolytic activity in a large number of campylobacters (94%) suggests its potential role as a virulence factor in campylobacter gastroenteritis. PMID- 7884799 TI - Characteristics of invasion of HEp-2 cells by Providencia alcalifaciens. AB - Previous studies with three isolates from diarrhoeal stools suggested that Providencia alcalifaciens is an invasive enteric pathogen that also causes actin condensation in infected cells. These findings were extended in the present study with a further 14 diarrhoeal stool isolates of P. alcalifaciens and HEp-2 cell monolayers for invasion assays. Studies on invasion characteristics with two selected isolates suggested that P. alcalifaciens required prior growth at 37 degrees C for better invasion. Invasion and actin condensation were inhibited by an agent that inhibits microfilament formation, but not by agents that inhibit receptor-mediated endocytosis, microtubule formation, endosome acidification or receptor recycling. In time-course assays with HEp-2 cell monolayers maintained in medium containing gentamicin, P. alcalifaciens showed a small degree of multiplication after invasion of the cells, but viable bacteria could not be recovered over a 24-h period although the integrity of the cell monolayer was preserved during this period. PMID- 7884800 TI - Replication of Chlamydia trachomatis and C. pneumoniae in the human monocytic cell line U-937. AB - To elucidate whether Chlamydia trachomatis and C. pneumoniae infections occur to a significant extent in monocytes-macrophages, the human monocytic cell line, U 937, was infected with C. trachomatis L2 or C. pneumoniae TW-183. Chlamydial DNA and genus-specific antigens of the lipopolysaccharides (LPS) in epitopes of the chlamydial cell wall were detected from C. trachomatis L2-inoculated monocytes over a period of 150 days after inoculation and from the C. pneumoniae TW-183 inoculated cells during a period of 14 days. C. trachomatis-infected U-937 cells expressed significantly lower levels of CD4+, CD45RA+, CD11b+ and CD33+ cells, determined by flow cytometry, than control uninoculated cells on the seventh day after inoculation and they expressed a slightly increased level of CD4+ cells and lower levels of CD45RA+ and CD11b+ cells on the 14th day after inoculation. C. pneumoniae-infected U-937 cells expressed significantly lower levels of CD4+, CD45RA+, CD11b+ and CD33+ cells than controls on the seventh day after inoculation and an increased level of CD4+ and a lower level of CD45RA+ cells on the 14th day after inoculation. Unlike infection with C. trachomatis L2 strain, chronic persistent infection with C. pneumoniae appears not to occur in monocytes macrophages. PMID- 7884801 TI - The chemotactic response of blood neutrophils and monocytes to strains of Escherichia coli with different virulence characteristics. AB - Chemotactic responses of blood neutrophils and monocytes to media conditioned by eight strains of Escherichia coli with different virulence characteristics were measured in modified Boyden assay chambers to determine if these characteristics were associated with differences in leucocyte mobility. Responding neutrophils and monocytes were prepared on conventional density gradients, and in three instances, the chemotaxis of eosinophils isolated on metrizamide gradients was also studied. Media conditioned by enteroinvasive and nonenteroinvasive E. coli strains were tested as chemo-attractants and compared to the formylated peptide standard attractant. Chemotactic activity of neutrophils was greater than that of monocytes and eosinophils, and migration by all populations was significantly greater to conditioned media than to the control medium. Chemotactic responses to media conditioned by non-enteroinvasive E. coli and strains lacking virulence factors was greater than to media conditioned by plasmid- and Sereny-positive enteroinvasive organisms. The results suggest that virulence factors of E. coli that determine invasiveness did not augment the chemotactic responses of the leucocyte populations tested in vitro, and give no support to the hypothesis that they induce mucosal inflammation by directly increasing chemotaxis in vivo. PMID- 7884802 TI - Immunogenic properties of Brucella melitensis cell-wall fractions in BALB/c mice. AB - The immunogenicity of several Brucella melitensis cell-wall (CW) fractions was tested in BALB/c mice. These CW fractions were smooth lipopolysaccharide (S-LPS) fraction from smooth (S) B. melitensis strain 16M, sodium dodecyl sulphate insoluble (SDS-I) CW fraction from B. melitensis strain 16M (S) undigested or digested with pepsin, and SDS-I CW fraction from rough (R) B. melitensis strain H38. The B. melitensis SDS-I CW fraction contained two major outer-membrane proteins (OMPs) of 25-27 kDa and 31-34 kDa, peptidoglycan (PG) and a small quantity (1.5%) of LPS. One month after immunisation, mice were challenged with virulent B. melitensis strain H38 (S) and Brucella spleen counts were recorded on days 28 and 49 after challenge. Before challenge, as measured by ELISA, the highest antibody responses to S-LPS were observed in mice immunised with SDS-I CW fraction from B. melitensis strain 16M (S), whether digested with pepsin or undigested. All immunised mice, except those immunised with the SDS-I CW fraction from the R strain, showed higher IgG1 than IgG2a antibody responses to S-LPS (IgG1:IgG2a ratio 3.64-7.71). Antibody responses to the 25-27-kDa OMP were very low, with the highest responses in the mice immunised with the SDS-I CW fraction from the R strain. These results indicated that, in BALB/c mice, these CW fractions probably induced Th2-dependent more than Th1-dependent antibody responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884803 TI - The use of a nested polymerase chain reaction for detecting Pneumocystis carinii from lung and blood in rat and human infection. AB - A nested polymerase chain reaction (PCR) assay was developed to detect both rat- and human-derived Pneumocystis carinii DNA. The nested PCR product was 125 bp long and was representative of part of the gene coding for the large subunit of mitochondrial ribosomal RNA. Twenty serial blood samples and 24 tissues from six immunosuppressed Sprague-Dawley rats were examined by nested PCR. All lung samples were positive by PCR and Toluidine blue O staining. Buffy coat samples and all the other tissues were PCR-negative during up to 6 weeks of immunosuppression. Thirty-five clinical bronchoalveolar lavage, induced sputum or tracheal aspirate samples from human patients were tested. Twelve of 35 were positive by both PCR and indirect fluorescence assay (IFA) and 19 of 35 were both PCR- and IFA-negative. Four of 35 were IFA-negative but PCR-positive and there were good responses in these patients to specific therapy, indicating that PCR may be more useful than IFA in clinical samples. P. carinii DNA was not detected in three blood samples. The nested PCR is a sensitive and specific DNA amplification method suitable for the routine diagnosis of P. carinii in human respiratory samples. PMID- 7884804 TI - Mechanisms of 4-quinolone resistance in quinolone-resistant and methicillin resistant Staphylococcus aureus isolates from Japan and China. AB - Ninety-two and 33 methicillin-resistant Staphylococcus aureus (MRSA) strains were isolated in Japan and China respectively. They were categorised as ofloxacin susceptible (MIC < 12.5 mg/L), moderately (MIC 12.5-25 mg/L) or highly (MIC > or = 50 mg/L) ofloxacin-resistant. 4-Quinolone concentrations required to inhibit purified DNA gyrase from the moderately and highly quinolone-resistant MRSA were at least 20 times higher than those required to inhibit the equivalent enzyme from quinolone-susceptible strains. Reconstitution assays demonstrated that the 4 quinolone-resistant MRSA had a mutation in subunit A of DNA gyrase. A portion of the gyrA gene from amino acids codons 40-115 was sequenced. Four moderately resistant and seven highly resistant MRSA contained a Ser-->Leu substitution at amino acid 84; one moderately and one highly resistant MRSA and one moderately resistant methicillin-susceptible S. aureus (MSSA) strain contained a Glu-->Lys substitution at amino acid 88. Eight MRSA, including one quinolone-susceptible strain and one MSSA contained a silent mutation at amino acid 86. Uptake of ofloxacin in moderately resistant strains was almost the same in the presence or absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), whereas in highly resistant strains, uptake increased when CCCP was added. Restriction fragment length analysis of the norA gene with the restriction endonuclease SfcI showed a mutation of nucleotide position 1085 in all MRSA strains tested except for one highly quinolone-resistant strain. Thus the mechanisms of 4-quinolone-resistance in these MRSA isolates involved alterations in both DNA gyrase and antimicrobial uptake and efflux. PMID- 7884805 TI - Mixed morphotype testing of Pseudomonas aeruginosa cultures from cystic fibrosis patients. AB - Bronchial secretions of patients with cystic fibrosis (CF) inevitably become colonised with Pseudomonas aeruginosa. This organism often exhibits multiple phenotypes with different antibiotic susceptibility profiles. Isolating each colonial morphotype and determining its antibiotic susceptibility profile is labour-intensive and time-consuming. Two disk diffusion methods for mixed morphotype susceptibility testing were examined; 134 morphotypes of P. aeruginosa from 50 respiratory specimens from CF patients were tested. Mixed cultures were prepared by (a) combining morphologically different colonies of P. aeruginosa directly from the sputum specimen primary culture plates from individual patients or (b) mixing colonies of individual morphotypes after isolation and subculture. Agreement with the results for testing morphotypes individually were 85.8% and 91.6%, respectively, for the two methods. These agreement rates rose to 95.6% and 99.4%, respectively, when minor errors (intermediate misclassified as susceptible or resistant or vice versa) were excluded. Mixed morphotype testing of P. aeruginosa directly from sputum specimen culture plates in chronically colonised CF patients is more efficient, reduces turn-around time and provides clinically meaningful information about antibiotic susceptibility. PMID- 7884806 TI - Non-opsonic phagocytosis of Trichophyton mentagrophytes arthroconidia by human neutrophils in vitro. AB - A non-opsonic mechanism of binding and phagocytosis by human neutrophils of Trichophyton mentagrophytes arthroconidia is described. This was in direct contrast to the complement dependency of Candida albicans phagocytosis. Both serum complement and specific antibody to T. mentagrophytes promoted maximal phagocytosis (61% and 40% of neutrophils, respectively, contained arthroconidia). Increasing the ratio of arthroconidia to neutrophils did not increase non-opsonic phagocytosis (18-26%). Phagocytosis of arthroconidia exposed to trypsin in the absence of opsonin was not affected (18%). However, proteinase and chitinase reduced the level of non-opsonic and opsonic phagocytosis to negligible levels (6.3% and 4.5%, respectively). When mannose was added to neutrophils, mannose receptors on the phagocyte membrane were partially blocked when arthroconidia were opsonised, but this did not reduce the level of non-opsonic phagocytosis. The non-opsonic mechanism proposed here may have direct relevance in skin sites poor in opsonins. PMID- 7884808 TI - Phenylglucosides and the Na+/glucose cotransporter (SGLT1): analysis of interactions. AB - Phenylglucosides are transported by the intestinal Na+/glucose cotransporter (SGLT1) and phlorizin, the classical competitive inhibitor of SGLT1, is also a phenylglucoside. To investigate the structural requirements for binding of substrates to SGLT1, we have studied the interactions between phenylglucosides and the cotransporter expressed in Xenopus oocytes using tracer uptake and electrophysiological methods. Some phenylglucosides inhibited the Na(+)-dependent uptake of 14C-alpha-methyl-D-glucopyranoside (alpha MDG) with apparent Kis in the range 0.1 to 20 mM, while others had no effect. Electrophysiological experiments indicated that phenylglucosides can act either as: (1) transported substrates, e.g., arbutin; (2) nontransported inhibitors, e.g., glucosylphenyl isothiocyanate; or (3) noninteracting sugars, e.g., salicin. The transported substrates (glucose, arbutin, phenylglucoside and helicin) induced different maximal currents, and computer simulations showed that this may be explained by a difference in the translocation rates of the sugar and Na(+)-loaded transporter. Computational chemistry indicated that all these beta-phenylglucosides have similar 3-D structures. Analysis showed that among the side chains in the para position of the phenyl ring the -OH group (arbutin) facilitates transport, but the -NCS (glucosylphenyl-isothiocyanate) inhibits transport. In the ortho position, -CH2OH (salicin) prevents interaction, but the aldehyde (helicin) permits the molecule to be transported. Studies such as these may help to understand the geometry and nature of glucoside binding to SGLT1. PMID- 7884807 TI - How proteins cross the bacterial cytoplasmic membrane. PMID- 7884809 TI - Calcium-mobilizing agonists stimulate anion fluxes in cultured endothelial cells from human umbilical vein. AB - The goal of the present studies was to determine whether anion fluxes are involved in thrombin- and histamine-activated signal transduction pathways in human umbilical vein endothelial cells (HUVECs). 125Iodine (125I) efflux techniques were used to test the sensitivity of anion fluxes to increases in [Ca2+]i and activation of protein kinase C. HUVECs exhibited constant 125I efflux rates under basal conditions. Administration of thrombin or histamine stimulated an increase in 125I efflux rates which returned to control values after approximately 1-2 min. Since both agonists stimulate increases in [Ca2+]i, we tested the hypothesis that 125I efflux was sensitive to changes in [Ca2+]i. When HUVECs were exposed to ionomycin or thapsigargin, the 125I efflux rate increased and remained elevated for several minutes. In subsequent experiments, HUVECs were incubated with the cell permanent Ca2+ chelator, 1,2-bis-(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid-AM, to buffer changes in [Ca2+]i. This treatment reduced both basal and thrombin-stimulated 125I efflux. However, when Ca2+ was removed from the efflux buffer and replaced with EGTA, peak thrombin-stimulated 125I efflux remained unchanged. This anion efflux was also sensitive to activation of protein kinase C since phorbol 12-myristate 13-acetate and phorbol, 12,13-dibutyrate blunted thrombin-mediated increases in 125I efflux. Preincubation of HUVECs with protein kinase C inhibitor peptide [19-36] antagonized the phorbol ester-mediated decrease in thrombin-stimulated 125I efflux. We suggest that 125I efflux in HUVECs represents a Ca(2+)-sensitive anion conductance and that intracellular Ca2+ release, but not extracellular Ca2+ influx, is sufficient to initiate channel activity. PMID- 7884810 TI - Hypotonically activated chloride current in HSG cells. AB - Hypotonically induced changes in whole-cell currents and in cell volume were studied in the HSG cloned cell line using the whole-cell, patch clamp and Coulter counter techniques, respectively. Exposures to 10 to 50% hypotonic solutions induced dose-dependent increases in whole-cell conductances when measured using K+ and Cl- containing solutions. An outward current detected at 0 mV, corresponded to a K+ current which was transiently activated, (usually preceding activation of an inward current and had several characteristics in common with a Ca(2+)-activated K+ current we previously described in these cells. The hypotonically induced inward current had characteristics of a Cl- current. This current was inhibited by NPPB (5-nitro-2-(3-phenyl-propylamino)-benzoate) and SITS (4-acetamido-4'-isothiocyanostilbene), and its reversal potentials corresponded to the Cl- equilibrium potentials at high and low external Cl- concentrations. The induced current inactivated at voltages greater than +80 mV, and the I-V curve was outwardly rectifying. The current was unaffected by addition of BAPTA or removal of GTP from the patch pipette, but was inhibited by removal of ATP or by the presence of extracellular arachidonic acid, quinacrine, nordihydroguairetic acid, and cytochalasin D. Moreover, exposure of HSG cells to hypotonic media caused them to swell and then to undergo a regulatory volume decrease (RVD) response. Neither NPPB, SITS or quinine acting alone could inhibit RVD, but NPPB and quinine together totally inhibited RVD. These properties, plus the magnitudes of the induced currents, indicate that the hypotonically induced K+ and Cl- currents may underlie the RVD response. Cytochalasin D also blocked the RVD response, indicating that intact cytoskeletal F-actin may be required for activation of the present currents. Hence, our results indicate that hypotonic stress activates K+ and Cl- conductances in these cells, and that the activation pathway for the K+ conductance apparently involves [Ca2+], while the activation pathway for the Cl- conductance does not involve [Ca2+] nor lipoxygenase metabolism, but does require intact cytoskeletal F-actin. PMID- 7884811 TI - Quinine and quinidine inhibit and reveal heterogeneity of K-Cl cotransport in low K sheep erythrocytes. AB - Low K (LK) sheep red blood cells (SRBCs) serve as a model to study K-Cl cotransport which plays an important role in cellular dehydration in human erythrocytes homozygous for hemoglobin S. Cinchona bark derivatives, such as quinine (Q) and quinidine (QD), are effectively used in the treatment of malaria. In the present study, we investigated in LK SRBCs, the effect of various concentrations of Q and QD on Cl-dependent K efflux and Rb influx (K(Rb)-Cl flux), activated by either swelling in hyposmotic media, thiol alkylation with N ethylmaleimide (NEM), or by cellular Mg (Mgi) removal through A23187 in the presence of external chelators. K efflux or Rb influx were determined in Cl and NO3 medium and K(Rb)-Cl flux was defined as the Cl-dependent (Cl minus NO3) component. K(Rb)-Cl flux stimulated by all three interventions was inhibited by both Q and QD in a dose-dependent manner. Maximum inhibition of K(Rb)-Cl flux occurred at Q and QD concentrations > or = 1 mM. The inhibitory effect of Q was manifested in Cl, but not in NO3, whereas QD reduced K and Rb fluxes both in Cl and NO3 media. The mean 50% inhibitory concentration (IC50) of Q and QD to inhibit K(Rb)-Cl flux varied between 0.23 and 2.24 mM. From determinations of the percentages of inhibition of the different components of K and Rb fluxes, we found that SRBCs possess a Cl-dependent QD-sensitive and a Cl-dependent QD insensitive K efflux and Rb influx. These two components vary in magnitude depending on the manipulation and directional flux, but in average they are about 50% of the total Cl-dependent flux. This study raises the possibility that, in SRBCs, the Cl-dependent K(Rb) fluxes are heterogeneous. PMID- 7884813 TI - Parameters affecting fusion between liposomes and synaptosomes. Role of proteins, lipid peroxidation, pH and temperature. AB - We investigated the effect of several parameters, such as temperature, pH and proteins, on the fusion between synaptosomes, freshly isolated from rat brain cortex, and large unilamellar phosphatidylserine liposomes. These studies were carried out in both peroxidized and nonperoxidized synaptosomes. Mixing of membrane lipids was monitored using a fluorescence resonance energy transfer assay. Ascorbate (0.8 mM)/Fe2+ (2.5 microM)-induced peroxidation of synaptosomes enhanced the fusion process (twofold) which may reflect an increase in synaptosomal protein hydrophobicity and hence a facilitation of intermembrane aggregation. The fusion process was shown to be temperature sensitive, a reduction in the extent being observed (twofold) as the temperature was lowered from 37 to 25 degrees C. This effect may be due to changes in membrane fluidity. The fusion process is pH dependent, an increase in both kinetics and extent being observed when the pH was lowered from 7.4 to 5.5. A significant inhibition (92% at pH 7.4; 35% at pH 5.5) of the interaction between synaptosomes and liposomes by trypsin pretreatment of synaptosomes was found, thus indicating that the fusion reaction is a protein-mediated process. The inhibitory effect of trypsin at pH 5.5 is not so strong as that at physiological pH. These results suggest that, in addition to the involvement of proteins, nonspecific interactions between the synaptosomal and liposomal membranes under acidic conditions may also play a role in the fusion process. The investigation of binding of synaptosomes to liposomes under several experimental conditions provided evidence for the participation of proteins in membrane aggregation, as well as for the role of electrostatic forces in this process, at mild acidic pH. PMID- 7884812 TI - The effect of intracellular Ca2+ on GABA-activated currents in cerebellar granule cells in culture. AB - The patch clamp technique was used to study the effects of intracellular free calcium ([Ca2+]i) on GABAA-evoked whole-cell and single channel currents of cultured cerebellar granule cells. Changes in [Ca2+]i were obtained by adding to the extracellular solution the calcium ionophore A23187 (2 microM). The relationship between [Ca2+]i and [Ca2+]o in the presence or absence of A23187 was assessed using fluorimetric measurements from Fura-2 loaded cells. In 2 mM [Ca2+]o and A23187, [Ca2+]i was about 1.5 microM, whereas in the absence of A23187 it was about 250 nM. In whole-cell experiments (symmetrical chloride concentrations) at -50 mV, GABA (0.5 microM) evoked inward currents that did not desensitize. Bath application of A23187 significantly reduced the steady-state amplitude of GABA currents by 37 +/- 6%. Single channel currents activated by GABA (0.5 microM) were also recorded in the outside-out configuration of the patch clamp technique. Kinetic analysis of single channel events revealed that A23187 significantly increased the long closed time constant (tau c3) without affecting the open time constants (tau o1 and tau o2) or the short and medium closed time constants (tau c1 and tau c2). Moreover, application of A23187 induced a significant reduction of burst duration (tau b). We conclude that a rise in [Ca2+]i by A23187 may decrease the binding affinity of GABA for the GABAA receptor. PMID- 7884814 TI - Cheek cell membrane fluidity measured by fluorescence recovery after photobleaching and steady-state fluorescence anisotropy. AB - Membrane fluidity of human cheek cells was determined using fluorescence recovery after photobleaching (FRAP) and steady-state fluorescence anisotropy. The FRAP data showed that the lateral diffusion coefficient (D) and mobile fraction (%R) of lipid in the plasma membrane of control cells were 2.01 x 10(-9) cm2/sec and 54.25%, respectively. Trypsin treatment increased D and %R to 6.4 x 10(-9) cm2/sec and 72.15%. In contrast, the anisotropy (r) for control cells was 0.270 which remained unchanged by trypsin treatment. The results show that diffusion of lipids in the plane of the membrane is restricted by trypsin-sensitive barriers. PMID- 7884815 TI - Veratridine triggers exocytosis in Paramecium cells by activating somatic Ca channels. AB - Paramecium tetraurelia wild-type (7S) cells respond to 2.5 mM veratridine by immediate trichocyst exocytosis, provided [Ca2+]o (extracellular Ca2+ concentration) is between about 10(-4) to 10(-3) M as in the culture medium. Exocytosis was analyzed by light scattering, light and electron microscopy following quenched-flow/freeze-fracture analysis. Defined time-dependent stages occurred, i.e., from focal (10 nm) membrane fusion to resealing, all within 1 sec. Veratridine triggers exocytosis also with deciliated 7S cells and with pawn mutants (without functional ciliary Ca channels). Both chelation of Ca2+o or increasing [Ca2+]o to 10(-2) M inhibit exocytotic membrane fusion. Veratridine does not release Ca2+ from isolated storage compartments and it is inefficient when microinjected. Substitution of Na+o for N-methylglucamine does not inhibit the trigger effect of veratridine which also cannot be mimicked by aconitine or batrachotoxin. We conclude that, in Paramecium cells, veratridine activates Ca channels (sensitive to high [Ca2+]o) in the somatic, i.e., nonciliary cell membrane and that a Ca2+ influx triggers exocytotic membrane fusion. The type of Ca channels involved remains to be established. PMID- 7884816 TI - Subnanomolar concentration of VIP induces the nuclear translocation of protein kinase C in neonatal rat cortical astrocytes. AB - At subnanomolar concentrations, vasoactive intestinal peptide (VIP) can act as an astroglial mitogen and as a secretagogue for neurotrophic substances released from glia (Brenneman et al.: J Neurosci Res 25:386-394, 1990). Here we report that treatment with subnanomolar (0.1 nM) VIP, that does not produce an increase in intracellular cAMP levels, induced the translocation of protein kinase C (PKC) from the cytoplasm to the nucleus in neonatal cortical astrocytes, as revealed by immunohistochemistry, Western blot analysis, and measurements of the enzyme activity. Western blot analysis of subcellular fractions, using PKC isotype specific antisera, showed PKC alpha as well as the two novel PKC isotypes, delta and zeta immunoreactivities, whereas PKC beta or gamma immunoreactivities were not detected. PKC alpha was associated predominantly with the cytosolic compartment, while PKC delta was found in the plasma membrane and in nuclear fractions. In contrast, PKC zeta was distributed ubiquitously within the major subcellular fractions. Treatment of the cells with 0.1 nM VIP caused a marked increase in nuclear PKC alpha and, to a lesser extent, PKC delta and PKC zeta immunoreactivities. Western blot analysis showed that a low (1 nM) concentration of phorbol, 12-myristate, 13 acetate also caused the subcellular redistribution of PKC immunoreactivities from the cytoplasm to the nuclear fraction, similar to VIP treatment. Exposure of astrocytes to high concentrations (1 microM) of phorbol, 12-myristate, 13 acetate resulted in the down-regulation of PKC alpha and PKC delta, while distribution of PKC zeta immunoreactivities were only slightly altered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884817 TI - Astroglia-released factor shows similar effects as benzodiazepine inverse agonists. AB - Media conditioned by cultured neonatal cerebral cortex microexplants (CCM) or astrocytes (ACM) contain low molecular weight (< 1,000 Da) substance(s) which inhibits the gamma aminobutyric acid (GABA)-induced inward current recorded in cerebellar granule cells and hippocampal neurons in culture using the whole-cell patch-clamp technique. This effect is specific for CCM and ACM, as medium conditioned by PC12 cells (PC12CM) does not affect the GABA response of these cells. It is also specific for GABA-induced currents because glutamate-induced currents do not change either in amplitude or in shape in the presence of CCM or ACM. The inhibitory effect on the GABA response in cerebellar granule cells of both ACM and CCM could be suppressed by flumazenil, a specific benzodiazepine (BZD) antagonist and could be mimicked by two BZD inverse agonists. These data thus demonstrate the presence of a BZD inverse agonist-like activity in CCM and ACM. This effect of ACM on different neuronal cell types was heterogenous since no detectable effect could be observed on the GABA-induced current in GABA responsive dorsal root ganglion (DRG) neurons, presumably reflecting a functional heterogeneity of the GABAA receptors present in these different neuronal subsets. By the release of such an endogenous BZD inverse agonist-like activity, glia cells could possibly modulate GABAA receptor-mediated responses. PMID- 7884818 TI - Isoprenylation of brain 2',3'-cyclic nucleotide 3'-phosphodiesterase modulates cell morphology. AB - CNP (2,3'-cyclic nucleotide 3'-phosphodiesterase) is the earliest myelination specific polypeptide to be synthesized by oligodendrocytes (OLs). When non myelinating "naive" cells are transfected with the rat CNP cDNA, CNP accumulates intracellularly in a punctate manner, as well as at the plasma membrane. Filopodia and processes, like those of OLs become elongated and more numerous, and are filled with this protein. Post-translational isoprenylation of the terminal C-T-I-I sequence with either farnesyl or geranylgeranyl is essential for this phenomenon. In contrast, the non-isoprenylated C397S mutant is homogeneously distributed throughout the cytoplasm and does not markedly affect cellular morphology. We have synthesized CNP and the C397S mutant in vitro and have shown that isoprenylation is essential for the binding of newly synthesized CNP to myelin. PMID- 7884819 TI - S100 beta protein expression in Alzheimer disease: potential role in the pathogenesis of neuritic plaques. AB - Increased synthesis and release of S100 beta protein from activated astrocytes has been implicated in the overgrowth of dystrophic neurites in neuritic plaques in Alzheimer disease (AD). To evaluate the quantitative relationships between tissues levels of S100 beta and the numbers of neuritic plaques in AD patients, we counted neuritic plaques, by Tau-2 immunoreactive (Tau-2+) labeling, in tissue sections of hippocampus and adjacent temporal cortex and measured the levels of S100 beta protein, by Western immunoblot labeling, in samples of analogous regions from contralateral hemisphere of the same patients. In AD, tissue levels of S100 beta (two- to fivefold that of controls) were significantly correlated with the number of Tau-2+ plaques (R = 0.82, P < .01). Dual-label immunohistochemical analysis showed that most S100 beta+ cells were activated GFAP+ astrocytes. These results were substantiated by a significant correlation between S100 beta and GFAP tissue levels (R = 0.81, P < .05). Many of the S100 beta+ astrocytes were clustered around and within Tau-2+ plaques. Indeed, no Tau 2+ plaques were found without associated activated S100 beta+ astrocytes. Our findings provide further evidence of a role for S100 beta protein in dysregulation of neurons that leads to apparently nonsensical growth of imperfect neurites in AD, a potential key element in early stages of neuritic plaque pathogenesis. PMID- 7884820 TI - Presence and regulation of transforming growth factor beta mRNA and protein in the normal and lesioned rat sciatic nerve. AB - The transforming growth factors beta (TGF-beta), a family of regulatory polypeptides, are involved in numerous vital processes including inflammation and wound healing. Since repair of a peripheral nerve lesion includes a series of well-defined steps of cellular actions possibly controlled by TGF-beta s, and since TGF-beta mRNA and immunoreactivity have been found in the normal peripheral nerve, we have examined in the lesioned peripheral nerve. Sciatic nerves of adult rats were either crushed (allowing axonal regeneration) or transfected (to prevent axonal regeneration and to induce Wallerian degeneration in the distal stump). After intervals of 6 hours, 2 and 6 days post-lesion, the rats were sacrificed and each nerve was cut into four segments, two proximal and two distal to the lesion site. TGF-beta 1-3 mRNA were determined for each segment. We demonstrate that TGF-beta 1 mRNA levels are higher than those of TGF-beta 3; the amplitude of mRNA regulation depends on time, type of lesion and localization relative to the lesion site. TGF-beta 2 mRNA could not be detected. For TGF-beta 1-3 immunocytochemistry, animals were sacrificed 12, 24, 48, 72 hours and 7 and 14 days after surgery. TGF-beta immunoreactivity (IR) was observed for all isoforms in lesioned and unlesioned nerves. In the segment directly adjacent to the lesion at its proximal side, an increase of TGF-beta-IR became apparent as soon as 12 hours after surgery; it remained elevated during the whole period observed in both models. In the segment adjoining the distal side of the lesion, an increase of TGF-beta-IR was observed after 48 hours, which was still present after 14 days. At day 7 after crush or transection, an increase of TGF-beta-IR was detected in the most distal segments, which reached its highest levels at the end of our observation period. Our results suggest that the presence of axonal contact might induce an enhancement of TGF-beta expression by Schwann cells in the distal stump of a lesioned and regenerating peripheral nerve. Since we demonstrate an increase of TGF-beta mRNA and protein expression also in the distal stump of transected nerves where Schwann cells are not able to contact sprouting axons from the proximal part, other regulatory pathways must exist. The acquisition of a "reactive" Schwann cell phenotype after peripheral nerve lesion might involve an upregulation of TGF-beta expression. PMID- 7884821 TI - omega-Conotoxin binding sites and regulation of transmitter release in cerebellar granule neurons. AB - The protective action of Ca2+ and a series of other divalent cations on heat inactivation (48 degrees C, 30 min) of [125I]omega-conotoxin (CTX) binding sites was investigated in membranes prepared from rat forebrain. Moreover, the influence of GABA (500 microM) on this protection was studied. Binding of [125I]CTX as well as its inhibitory action on K+ (55 mM) stimulated, Ca(2+) dependent transmitter release were studied in rat cerebellar granule neurons cultured in the presence or absence of the GABAA receptor against THIP (4,5,6,7 tetrahydroisoxazolo[5,4-c]pyridin-3-ol). In cells cultured in the presence of THIP (150 microM) it was investigated whether the ability of THIP to inhibit evoked transmitter release could be influenced by CTX. Ca2+ and other divalent cations could effectively protect against heat inactivation of [125I]CTX binding sites in rat forebrain membranes, but this protective action was not influenced by the presence of 500 microM GABA. The cultured cerebellar granule neurons exhibited specific binding sites for [125I]CTX, the number of which was independent of exposure of the cells to THIP during the culture period. Evoked transmitter release was inhibited by CTX with an IC50 value of 13 nM. In neurons cultured in the presence of 150 microM THIP, THIP could dose-dependently inhibit evoked transmitter release, but this inhibitory action was not influenced by CTX (20 nM). The results show that cerebellar granule neurons exhibit functionally meaningful CTX binding sites. An association between such sites and GABA receptors is not apparent. PMID- 7884822 TI - Differential expression of alpha-actin mRNA and immunoreactive protein in brain microvascular pericytes and smooth muscle cells. AB - Hypertension has been linked to opening of the blood-brain barrier and may be related to the expression of the smooth muscle alpha-actin gene in contractile cells at the brain microvasculature. However, the cellular origin (i.e., endothelial cells, pericytes, smooth muscle cells) of the alpha-actin mRNA in the brain microvasculature is not clearly identified. Therefore, we investigated the abundance of actin mRNA by Northern blot analysis in isolated brain microvessels and in brain microvascular endothelial or pericytes in tissue culture. All samples showed the characteristic 2.1 kb transcript corresponding to cytoplasmic beta and gamma isoform mRNA. The 1.7 kb transcript corresponding to smooth muscle alpha-actin was detected in freshly isolated bovine brain microvessels, in primary cultures of brain microvascular pericytes, or endothelial cells; the latter cultures contain both endothelial cells and pericytes. The alpha-actin mRNA was absent in a cloned bovine brain endothelial cell line. The relative abundance of the alpha/(beta + gamma) actin transcript ratio was: cultured pericytes > freshly isolated microvessels > endothelial primary. The cellular distribution of the smooth muscle alpha-actin immunoreactive protein was studied by immunocytochemistry in cytospun/methanol-fixed isolated bovine brain microvessels with a monoclonal antibody directed to the amino-terminal decapeptide of the smooth muscle alpha-actin isoform. This antibody reacted strongly with precapillary arterioles of isolated microvessels, whereas no immunostaining was observed in either capillary endothelial cells or in pericytes. In conclusion, the alpha-actin mRNA is expressed in brain microvascular pericytes in tissue culture, but the immunoreactive alpha-actin protein is not expressed in brain microvascular pericytes in vivo. These data suggest that either 1) alpha-actin gene expression is induced in capillary pericytes in tissue culture or 2) alpha-actin mRNA in brain capillary pericytes in vivo is subject to translational repression resulting in no detectable alpha actin protein under normal conditions. PMID- 7884823 TI - Enhanced aggregation and beta structure of amyloid beta peptide after coincubation with C1q. AB - Several lines of evidence now suggest that aggregation of soluble amyloid beta peptide (A beta) into a cross beta sheet configuration may be an important factor in mediating potential neurotoxicity of A beta. Synthetic A beta has been shown to self aggregate in vitro. Here, we demonstrate that coincubation of freshly solubilized A beta with C1q, a complement component known to bind A beta in vitro and to colocalize with A beta in vivo, results in as much as a 7-fold enhancement of A beta aggregation, as well as a 2-4-fold enhancement of beta structure within aggregates. The addition of C1q to preformed A beta aggregates also results in significantly increased resistance to aggregate resolubilization. PMID- 7884824 TI - Calpain inhibitors block Ca(2+)-induced suppression of neurite outgrowth in isolated hippocampal pyramidal neurons. AB - Ca2+ is an important regulator of neurite elongation and growth cone movements but the mechanism(s) mediating these Ca(2+)-dependent effects is unclear. Since cytoskeletal proteins are rapidly degraded by Ca(2+)-dependent proteinases (calpains) in vitro and in vivo, we investigated whether Ca(2+)-induced pruning or regression of neuronal processes is mediated by calpains. Isolated hippocampal pyramidal-like neurons were cultured and the ability of the membrane-permeable calpain inhibitors ethyl(+)-(2S,3S)-3-[(S)-methyl-1-(3-methylbutylcarbamoyl) butyl carbamoyl]-2 - oxiranecarboxylate (EST) and carbobenzoxyl-valyl phenylalanyl-H (MDL 28170) to block the Ca2+ ionophore A23187-induced suppression in neurite outgrowth was investigated. Addition of 100 nM A23187 to the culture medium resulted in a retraction of dendrites without altering axonal elongation. The addition of 300 nM A23187 to the culture medium resulted in a significant decrease in the rate of axonal elongation as well as a retraction of dendritic processes. Administration of EST (5 or 20 microM) to the culture medium completely blocked the pruning effect of 100 nM A23187 on dendrites and of 300 nM A23187 on axons, while EST alone did not significantly affect neurite outgrowth rate. MDL 28170 (20 microM) showed the same effect as EST in preventing ionophore induced pruning of dendrites and axons at 100 and 300 nM concentrations, respectively, of A23187. EST (20 microM) did not block the A23187-induced rise of [Ca2+]i as measured with fura-2. These results suggest that calpains play a role in Ca(2+)-induced pruning of neurites in isolated hippocampal pyramidal neurons. PMID- 7884825 TI - Human IMR-32 neuroblastoma cells as a model cell line in Alzheimer's disease research. AB - The present study investigated expression and processing of amyloid precursor protein by neuronally differentiated IMR-32 neuroblastoma cells. APP mRNA in these cells was found to consist of approximately 58% APP695, 38% APP751, and < 4% APP770. APP-immunoreactive bands detected in western blots of cellular protein extracts were only detected by anti-APP antibodies to peptides with strong homology to APLP2, suggesting that these bands represent APP-like proteins and not APP itself. This result suggests that previous studies claiming immunodetection of cellular forms of APP may have to be re-evaluated. Four main species of C-terminal truncated, secreted APP were detected in blots of protein extracts from medium conditioned by these cells. The immunoreactive profile of these bands suggested a cleavage site N-terminal to the Lys16-Leu17 bond of alpha secretase. This, together with differences in number and molecular mass of APP immunoreactive bands between secreted APP from IMR-32 cells and that from the commonly used PC-12 cells, suggests differences in APP processing between these two neuronally differentiated cell lines. In theory, IMR-32 cells being of human neuronal origin may be a more appropriate cell line to study APP-processing in relation to Alzheimer's disease than the rat phaeochromocytoma PC-12 cell line. Therefore, these detected differences warrant further investigation. Additionally IMR-32 cells under certain tissue culture conditions can form intracellular fibrillary material that reacts with anti-PHF specific antibodies. Neuronally differentiated IMR-32 cells could therefore be used as a model system to investigate possible interactions between APP-processing and PHF formation. PMID- 7884826 TI - Adenovirus-mediated gene therapy of experimental gliomas. AB - The efficacy of adenovirus (ADV)-mediated gene therapy to treat brain tumors was tested in a syngeneic glioma model. Tumor cells were transduced in situ with a replication-defective ADV carrying the herpes simplex virus thymidine kinase (HSV tk) gene controlled by the Rous sarcoma virus promoter. Expression of the HSV-tk gene enables the transduced cell to convert the drug ganciclovir to a form that is cytotoxic to dividing cells. Tumors were generated in Fischer 344 rats by stereotaxic implantation of 9L gliosarcoma cells into the caudate nucleus. Eight days later, the tumors were injected either with the ADV carrying the HSV-tk (ADV tk) gene or a control ADV vector containing the beta-galactosidase (ADV-beta gal) gene and the rats were treated with either ganciclovir or saline. Tumor size was measured 20 days after implantation of 9L cells or at death. Rats treated with ADV-beta gal and ganciclovir or with ADV-tk and saline had large tumors. No tumors were detected in animals treated with ADV-tk and with ganciclovir at doses > or = 80 mg/kg. An infiltrate of macrophages and lymphocytes at the injection site in animals treated with ADV-tk and ganciclovir indicated an active local immune reaction. In survival studies, all animals treated with ADV-tk and ganciclovir have remained alive longer than 80 and up to 120 days after tumor induction whereas all untreated animals died by 22 days. These results demonstrate that ADV-mediated transfer of HSV-tk to glioma cells in vivo confers sensitivity to ganciclovir, and represents a potential method of treatment of brain tumors. PMID- 7884827 TI - Effects of caffeine and related methylxanthines on fetal mouse palates cultured in vitro. AB - The maxillary regions of day-12.5 ICR mouse fetuses were cultured in a chemically defined serumless medium and the effects of methylxanthine derivatives on cultured palates were studied. Explanted palates were treated for 72 hr in vitro with 0.5-2 mM caffeine (CA), 1-2 mM theophylline (TP), or 1-2 mM theobromine (TB). Although the three compounds tested did not prevent the contact of opposing palatal shelves, palatal fusion was inhibited by CA and TP at a concentration of 2 mM, and the inhibitory effect of CA was more evident than that of TP. On the other hand, TB did not exert an inhibitory effect on palatogenesis at 2 mM. Since the in vitro toxicity of the methylxanthine compounds appeared to correlate well with their in vivo teratogenic potential, the organ culture method of fetal rodent palates should be a useful tool for screening teratogenic agents, especially those causing cleft palate. PMID- 7884828 TI - Effects of a daily feeding-restriction on the reproductive and development toxicity parameters in female rats. AB - On the assumption of that the oral administration of an acid-unstable test compound into the empty stomach could enhance the systemic exposure to the test compound, the non-pregnant and pregnant rats had free access to the diet only for five hours per day. Female rats under the restricted feeding for a period of 21 days took diet at two thirds of the daily food-intake by the control animals, and lost their weight more than 10%. The vaginal smear test in these animals revealed a prolonged estrous cycle and diestrous period over four days. On the other hand, the restricted feeding from Day 0 to Day 17 of gestation suppressed the weight gain of pregnant animals but did not cause any significant influence upon the litter data, incidence of external anomalies or fetal skeletal development. The restricted feeding from Day 0 of gestation to Day 7 of lactation seriously disturbed the nursing behavior and the growth of offspring. These results suggested that the dosing method under the above-mentioned restricted feeding might be applicable to the teratology study but could not be applied to the fertility study nor to the peri- and post-natal study. PMID- 7884829 TI - Inhibiting effects of diethylmaleate or NH4Cl on NaHCO3, but not butylated hydroxyanisole, promotion of urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine. AB - The modifying potential of diethylmaleate (DEM) and NH4Cl on promotion by butylated hydroxyanisole (BHA) or NaHCO3 of urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was investigated. Six week old animals received 0.05% BBN for 4 weeks and then BHA (2%) + DEM (0.15%), BHA + NH4Cl (1%), NaHCO3 (3%) + DEM, NaHCO3 + NH4Cl, BHA, DEM, NH4Cl or no supplement, administered during experimental weeks 5-36. BHA and NaHCO3 clearly amplify the induction of papillary or nodular (PN) hyperplasias and papillomas in rats initiated with BBN. The promoting activity of BHA was not affected by simultaneous administration of DEM or NH4Cl. The enhancing effects of NaHCO3, in contrast, were clearly diminished by concurrent administration of either of these agents. DEM itself did not influence lesion development whereas NH4Cl reduced the incidence of papillomas. In a second experiment, rats exposed to the same protocol were killed at week 8, and assessed for levels of lipid peroxides in the bladder tissue. No remarkable alterations were observed in any group. Thus, the fact that DEM did exert inhibiting effects on tumor promotion by NaHCO3 without decreasing the urinary sodium ion concentration or pH and influence on lipidperoxide levels, suggests essential differences in the mechanisms of action of different types of bladder promoters. PMID- 7884830 TI - The in vitro effect of 13 metals on the activity of erythrocyte pyrimidine 5' nucleotidase (P5N). AB - The in vitro effect of 13 metal ions on the activity of erythrocyte pyrimidine 5' nucleotidase (P5N) was investigated. Particular metals belonging to the boron group have recently been used as materials in a semi-conductor manufacturing. Of these metal ions, Ga exhibited no inhibition of erythrocyte P5N, while in extensively inhibited the erythrocyte P5N activity at concentrations of 10(-4) to 10(-3) M. In addition, the activity of erythrocyte P5N was inhibited by 90-96% when the metal ions such as Cu, Ag, Cd, Hg or Pb were added to the incubation mixture at concentrations of 10(-4) to 10(-3) M. On the other hand, there was no difference between sulfate and nitrate in the in vitro effect of the metal ions on the activity of erythrocyte P5N. PMID- 7884831 TI - Effects of phenobarbital on drug metabolizing enzyme activities and other biochemical parameters in rats with DL-ethionine-induced liver injury. AB - Phenobarbital (PB) was orally administered once at a dose of 100 mg/kg to the liver injury model rats treated with DL-ethionine (ET), and the effects of PB on the liver drug metabolizing enzymes (DME) were chiefly examined. Liver weight, liver microsomal protein content, liver aniline 4-hydroxylase (ANH) activity, and aminopyrine N-dimethylase (AMD) activity were markedly increased in the ET treated rats receiving PB. These findings suggested the induction of DME in the liver. However, the induction pattern of each enzyme was different. AMD activity at 48 hr after dosing of PB in the ET-treated rats was increased in the same degree as that in the control (normal). Whereas, ANH activity at 48 hr after dosing in the ET-treated rats was higher than that in normal rats. Liver lactate dehydrogenase (LDH) activity at 48 hr after dosing in the ET-treated rats was markedly increased, but such induction was not seen in normal rats. These findings indicates that DME in the liver is induced by PB treatment in the ET treated rats as well as in normal rats, and that the ET-treated rats have a function of physiological adaptation similar to that in normal rats. The induction pattern of liver or serum enzymes in the ET-treated rats receiving PB was different from that in normal rats. Furthermore, the induction pattern of these enzymes in the ET-treated rats receiving PB was different from that in the normal rats, which may be attributed to the difference of localization in liver cells of these enzymes affected by PB. PMID- 7884832 TI - Influence of efonidipine hydrochloride, calcium antagonist on the epithelium of prostates in spontaneously hypertensive rats. AB - The hypertensive effect on the development of the prostatic abnormality in spontaneously hypertensive rats (SHRs) was examined using Efonidipine hydrochloride, a calcium antagonist. The control SHRs were given a high sodium and potassium diet (SP-diet) alone, and the treated SHRs were given a SP-diet with 0.15% Efonidipine hydrochloride from 8 to 28 weeks of age. The systolic blood pressure (SBP) in the control SHRs increased with age, while the elevation of SBP was significantly prevented in the treated SHRs. Light-microscopically, the prostatic lesion was observed both in the control and treated SHRs. The glandular lumen was narrowed with papillary protrusions, and the epithelium was composed of tall columnar epithelial cells. However, hypertension-induced complications in kidneys and hearts were not observed in the treated SHRs. These results suggested that the prostatic abnormality of SHRs might not be the consequent lesions upon hypertension. PMID- 7884833 TI - Evidence of partial involvement of P-450 2D in mutagenic activation of benzo(a)pyrene in liver S-9 fraction from untreated rats. AB - In order to clarify which species of cytochrome P-450 is involved in activation of benzo(a)pyrene (BP) in untreated rat liver, strain and sex differences in the ability of rat liver 9000 g supernatant (S-9) to mutagenically activate BP was investigated using Ames test. The numbers of histidine revertants in Ames test after pre-incubation of TA 98 strain of Salmonella typhimurium and BP with liver S-9 from male rats were markedly higher than those obtained using female rats. In addition, a marked strain difference (Wistar > DA) in the ability of liver S-9 from Wistar and DA rats to activate BP was observed. Antibody against cytochrome P-450 2D inhibited up to 50% of the revertant formation by the activation of BP with liver S-9 from male Wistar rats. These results indicate the partial involvement of cytochrome P-450 2D subfamily as well as cytochrome P-450 species specific to male rats in activation of BP to ultimate mutagen in untreated rat liver. PMID- 7884834 TI - Shame, guilt, and depression in men and women in recovery from addiction. AB - Men and women in recovery from addiction were compared on levels of depression and self-conscious affect including proneness to shame, guilt, externalization, detachment, and pride. The sample consisted of 130 subjects (88 men and 42 women; mean age 33.04), 90 of whom were active participants in a 12-step recovery program, and 40 of whom were in a residential treatment community. Subjects completed The Beck Depression Inventory and The Test of Self-Conscious Affect. Significant differences between the sexes were found for proneness to shame, detachment, and depression. Women were significantly higher on shame and depression; men were significantly higher on detachment. The subjects were compared to subjects who were not chemically dependent. It was found that these recovering drug-addicted subjects scored significantly higher in proneness to shame and externalization and significantly lower on proneness to guilt. Treatment implications of proneness to shame in the drug-addicted population, and particularly in women, are discussed. The use of confrontational drug treatment strategies may be contraindicated. PMID- 7884835 TI - Gender-sensitive therapy. An alternative for women in substance abuse treatment. AB - This article examines internal and external factors that put women at risk of substance use/abuse. Gender-sensitive therapy is suggested as an effective treatment to deal with the intrapsychic causes of problems as well as societal expectations and oppression that contribute to women's thoughts and behaviors. The focus of therapy is on providing a caring, nurturing, and empowering environment for women to become independent decision makers. PMID- 7884836 TI - An enhanced positive reinforcement model for the severely impaired cocaine abuser. AB - This article describes a cognitive-behavioral treatment approach that has been extensively modified to work with inner-city methadone-maintained cocaine users. Modifications were deemed essential to address the problems of engagement and retention in treatment that are typically encountered with this population. While this approach relies on such basic tenets of treatment as relapse prevention, cognitive restructuring, and psychoeducation, an understanding of the particular psychological vulnerabilities of this population has been incorporated into the model. The modified approach utilizes positive reinforcement extensively. This includes use of concrete reinforcers to facilitate initial engagement, and use of interpersonal reinforcers (therapist positive regard, attention, and respect) to increase program retention and sustain posttreatment change. Preliminary results indicate that 63% of patients can complete this intensive 6-month program, with considerable reductions in cocaine use and significant change in drug injection behavior. PMID- 7884837 TI - Reliability and validity of the Addiction Severity Index with a homeless sample. AB - The Addiction Severity Index (ASI) is an instrument widely used to assess the treatment problems of substance users. Its psychometric properties have been tested and found satisfactory for many types of substance abusers entering treatment. However, there are many other subgroups of substance users not in formal treatment, such as homeless substance users. While the ASI has been used with this subgroup, its psychometric properties remain questionable. This study examined the reliability and validity of the ASI in a sample of 98 homeless substance users awaiting temporary housing placement. Test-retest reliability found the ASI to have moderate to high reliability coefficients in each of the seven domains assessed. Both composite score and severity rating measures were found to be quite independent with low intercorrelations. Three of the seven ASI composite scores were tested for and found to have moderate concurrent validity: alcohol (r = .31 to .36), drug (r = .46), and psychiatric (r = .53 to .66). Composite score interitem correlations were .70 or greater in each of the domains except for employment (.50) and family (.52). These data suggest that, although there are some limitations in using the ASI with homeless substance users, it demonstrated acceptable reliability and validity. PMID- 7884838 TI - Cue-elicited cocaine craving and autogenic relaxation. Association with treatment outcome. AB - Prior to entering a pharmacotherapy trial for the treatment of cocaine dependence, 19 patients participated in a pretreatment cue-reactivity protocol that concluded with a relaxation exercise. Measures included self-reported craving and skin conductance level (SCL). Post hoc exploratory analyses suggest that neither craving nor change in SCL in response to cocaine cues differentiated patients who subsequently achieved abstinence from those who did not. Craving following the relaxation procedure did differentiate the two groups: patients who subsequently initiated abstinence in treatment reported a reduction in cue elicited craving to below baseline levels; craving reported by patients who did not successfully complete treatment remained elevated. PMID- 7884839 TI - Assessing adolescent substance use: a critique of current measurement instruments. AB - A variety of instruments are currently available to screen for and assess adolescent substance abuse and aid in planning appropriate interventions. Assessment practices in treatment facilities for adolescents have tended to rely on the use of unstandardized, local measures or on measures developed for adults with unknown reliability and validity for adolescents. This review is designed to serve as a resource for health professionals regarding the issues involved in assessing adolescent substance involvement and the types of instruments that are available for use. Conceptual issues relevant to the evaluation of adolescent substance use are discussed. Then, standardized, adolescent-specific assessment tools are briefly summarized, including screening questionnaires, comprehensive instruments, and several other substance-related instruments. PMID- 7884840 TI - A naturalistic follow-up study of French-speaking opiate-maintained heroin addicted patients: effect on biopsychosocial status. AB - The purpose of this study was to evaluate the impact of opiate maintenance pharmacotherapy (OMP) on the biopsychosocial status of opiate-addicted patients in a cultural environment (France) that is not favorable to OMP and where methadone is not available. Buprenorphine and laudanum (opium tincture), which, to our knowledge, has not been reported previously in the scientific literature for OMP, were used in this study of a group of 18 opioid-dependent subjects. At time of initiation of OMP, mean age was 33 years, sex ratio male: female was 14:4, average duration of drug use was 11.2 years. Six patients received laudanum p.o., 15 g daily; 12 patients received buprenorphine sublingual 2 to 4 mg daily. This group of patients was selected because of persistent relapse and impairment after an average of 5.7 drug-free-oriented treatments over a period of 6.8 years. Initial evaluation and follow-up were made by way of a 150-min semi-structured interview using the Lifetime Retrospective Evaluation Score Table (LREST) and the Addiction Severity Index (ASI). Results showed that body weight and scores for physical and psychological health, socioprofessional status, and family relationships improved significantly after 14 months of OMP. These results show that highly impaired opiate-addicted patients doing poorly in drug-free treatment can respond to OMP even though methadone is not available and the idea of OMP is not favored. PMID- 7884841 TI - Treating college substance abusers. The New Jersey Collegiate Substance Abuse Program. AB - University students with serious substance use disorders may require specialized treatment. The New Jersey Collegiate Substance Abuse Program (NJCSAP) was a treatment center developed for this population that allowed students to receive treatment while remaining in the university environment and continuing school. NJCSAP was structured into three levels of care so that clients could be matched to treatment of appropriate intensity. In addition, NJCSAP helped students develop a network of supportive recovering peers and activities on the Rutgers University campus. An evaluation of the client population revealed a group of students with a history of severe substance use and related problems. Implications of the evaluation results are discussed. PMID- 7884842 TI - A comprehensive strategy for improving drug abuse treatment. PMID- 7884843 TI - Acupuncture has been used primarily as an adjunct to existing chemical dependency treatment protocols. PMID- 7884844 TI - Formation of the flavivirus envelope: role of the viral NS2B-NS3 protease. AB - One of the late processing events in the flavivirus replication cycle involves cleavage of the intracellular form of the flavivirus capsid protein (Cint) to the mature virion form (Cvir) lacking the carboxy-terminal stretch of hydrophobic amino acids which serves as a signal peptide for the downstream prM protein. This cleavage event was hypothesized to be effected by a viral protease and to be associated with virion formation. We have proposed a model of flavivirus virion formation in which processing of the C-prM precursor at the upstream signalase site is upregulated by interaction of the NS2B part of the protease with the prM signal peptide or with an adjacent carboxy-terminal region of the capsid protein in the precursor, and processing of Cint by the NS2B-NS3 protease follows the signalase cleavage. Recently, an alternative hypothesis was proposed which suggests a reverse order of these two cleavage events, namely, that cleavage of the C-prM precursor by the NS2B-NS3 protease at the Cint-->Cvir dibasic cleavage site is a prerequisite for the subsequent signalase cleavage of the prM signal peptide. To distinguish between these alternative models, we prepared a series of expression cassettes carrying mutations at the Cint-->Cvir dibasic cleavage site and investigated the effects of these mutations on signalase processing of C-prM and on formation and secretion of prM-E heterodimers. For certain mutated C-prM precursors, namely, for those with Lys-->Gly disruption of the dibasic site, efficient formation of prM was observed upon expression from larger cassettes encoding the viral protease, despite the absence of processing at the Cint-->Cvir cleavage site. Surprisingly, formation and secretion of prM-E heterodimers accompanied by late cleavage of prM was also observed for these cassettes, with an efficiency comparable to that of the wild-type expression cassette. These observations contradict the model in which cleavage of the C-prM precursor at the Cint-->Cvir dibasic site is a prerequisite for signalase cleavage. PMID- 7884845 TI - Cellular and humoral immune responses to viral antigens create barriers to lung directed gene therapy with recombinant adenoviruses. AB - Recombinant adenoviruses are an attractive vehicle for gene therapy to the lung in the treatment of cystic fibrosis (CF). First-generation viruses deleted of E1a and E1b transduce genes into airway epithelial cells in vivo; however, expression of the transgene is transient and associated with substantial inflammatory responses, and gene transfer is significantly reduced following a second administration of the virus. In this study, we have used mice deficient in immunological effector functions in combination with adoptive and passive transfer techniques to define antigen-specific cellular and humoral immune responses that underlie these important limitations. Our studies indicate that major histocompatibility complex class I-restricted CD8+ cytotoxic T lymphocytes are activated in response to newly synthesized antigens, leading to destruction of virus infected cells and loss of transgene expression. Major histocompatibility complex class II-associated presentation of exogenous viral antigens activates CD4+ T-helper (TH) cells of the TH1 subset and, to a lesser extent, of the TH2 subset. CD4+ cell-mediated responses are insufficient in the absence of cytotoxic T cells to completely eliminate transgene containing cells; however, they contribute to the formation of neutralizing antibodies in the airway which block subsequent adenovirus-mediated gene transfer. Definition of immunological barriers to gene therapy of cystic fibrosis should facilitate the design of rational strategies to overcome them. PMID- 7884846 TI - Specific binding of host cellular proteins to multiple sites within the 3' end of mouse hepatitis virus genomic RNA. AB - The initial step in mouse hepatitis virus (MHV) RNA replication is the synthesis of negative-strand RNA from a positive-strand genomic RNA template. Our approach to begin studying MHV RNA replication is to identify the cis-acting signals for RNA synthesis and the proteins which recognize these signals at the 3' end of genomic RNA of MHV. To determine whether host cellular and/or viral proteins interact with the 3' end of the coronavirus genome, an RNase T1 protection/gel mobility shift electrophoresis assay was used to examine cytoplasmic extracts from mock- and MHV-JHM-infected 17Cl-1 murine cells for the ability to form complexes with defined regions of the genomic RNA. We demonstrated the specific binding of host cell proteins to multiple sites within the 3' end of MHV-JHM genomic RNA. By using a set of RNA probes with deletions at either the 5' or 3' end or both ends, two distinct binding sites were located. The first protein binding element was mapped in the 3'-most 42 nucleotides of the genomic RNA [3' (+42) RNA], and the second element was mapped within an 86-nucleotide sequence encompassing nucleotides 171 to 85 from the 3' end of the genome (171-85 RNA). A single potential stem-loop structure is predicted for the 3' (+)42 RNA, and two stem-loop structures are predicted for the 171-85 RNA. Proteins interacting with these two elements were identified by UV-induced covalent cross-linking to labeled RNAs followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The RNA-protein complex formed with the 3'-most 42 nucleotides contains approximately five host polypeptides, a highly labeled protein of 120 kDa and four minor species with sizes of 103, 81, 70, and 55 kDa. The second protein-binding element, contained within a probe representing nucleotides 487 to 85 from the 3' end of the genome, also appears to bind five host polypeptides, 142, 120, 100, 55, and 33 kDa in size, with the 120-kDa protein being the most abundant. The RNA-protein complexes observed with MHV infected cells in both RNase protection/gel mobility shift and UV cross-linking assays were identical to those observed with uninfected cells. The possible involvement of the interaction of host proteins with the viral genome during MHV replication is discussed. PMID- 7884847 TI - Characterization of an infectious molecular clone of human T-cell leukemia virus type I. AB - An infectious molecular clone of human T-cell leukemia virus type I (HTLV-I) was derived from an HTLV-I-transformed rabbit T-cell line, RH/K30, obtained by coculture of rabbit peripheral blood mononuclear cells (PBMC) with the human HTLV I-transformed cell line MT-2. The RH/K30 cell line contained two integrated proviruses, an intact HTLV-I genome and an apparently defective provirus with an in-frame stop codon in the env gene. A genomic DNA fragment containing the intact HTLV-I provirus was cloned into bacteriophage lambda (K30 phi) and subcloned into a plasmid vector (K30p). HTLV-I p24gag protein was detected in culture supernatants of human and rabbit T-cell and fibroblast lines transfected with these clones, at levels comparable to those of the parental cell line RH/K30. Persistent expression of virus was observed in one of these lines, RL-5/K30p, for more than 24 months. Biologic characterization of this cell line revealed the presence of integrated HTLV-I provirus, spliced and unspliced mRNA transcripts, and typical extracellular type C retrovirus particles. As expected, these virus particles contained HTLV-I RNA and reverse transcriptase activity. The transfected cells also expressed surface major histocompatibility complex class II, whereas no expression of this molecule was detected in the parental RL-5 cell line. Virus was passaged by cocultivation of irradiated RL-5/K30p cells with either rabbit PBMC or human cord blood mononuclear cells, demonstrating in vitro infectivity. The virus produced in these cells was also infectious in vivo, since rabbits injected with RL-5/K30p cells became productively infected, as evidenced by seroconversion, amplification of HTLV-I-specific sequences by PCR from PBMC DNA, and virus isolation from PBMC. Availability of infectious molecular clones will facilitate functional studies of HTLV-I genes and gene products. PMID- 7884848 TI - Molecular and biological analyses of quasispecies during evolution of a virulent simian immunodeficiency virus, SIVsmmPBj14. AB - A prototypic simian immunodeficiency virus (SIVsmm9), isolated from a naturally infected sooty mangabey (Cercocebus atys), was passaged in vivo in a pig-tailed macaque (Macaca nemestrina) having the identifier PBj. When PBj died of a typical AIDS-like syndrome 14 months after infection, the virus isolated from its tissues was subsequently shown to differ from SIVsmm9 genetically and biologically. Most notably, this isolate, SIVsmmPBj14 (SIV-PBj14), is the most virulent primate lentivirus known: it induces acute disease and death within 6 to 10 days after intravenous inoculation into pig-tailed macaques. Between the time of infection with SIVsmm9 and isolation of SIV-PBj14, isolates were obtained periodically from peripheral blood mononuclear cells of PBj. To establish the temporal relationship between evolution of new biologic properties and fixation of specific mutations in the virus population, these sequential SIV-PBj isolates were characterized for unique properties of SIV-PBj14 that appeared to correlate with acute lethal disease. These properties included the ability to replicate in quiescent macaque peripheral blood mononuclear cells, to activate and induce proliferation of CD4+ and CD8+ cells, and to exhibit cytopathicity for mangabey CD4+ lymphocytes. Consistent with earlier studies, a major change in biologic properties occurred between 6 (SIV-PBj6) and 10 (SIV-PBj10) months, with the SIV-PBj8 quasispecies exhibiting properties of both earlier and later isolates. Multiple biologic clones derived from the 6-, 8-, and 10-month isolates also exhibited diverse phenotypes. For example, one SIV-PBj10 biologic clone resembled SIVsmm9 phenotypically, whereas three other biologic clones resembled SIV-PBj14. To evaluate genetic changes, proviral DNA of the biologic clones generated from SIV PBj6, -PBj8, and -PBj10 was amplified by PCR in the U3 enhancer portion of the long terminal repeats (LTR) and the V1 region of env, where the greatest nucleotide diversity between SIVsmm9 and SIV-PBj14 resided. Nucleotide sequence data indicated that all biologically cloned viruses are distinct and that insertions/duplications of 3 to 27 nucleotides (in multiples of three) had accumulated stepwise in the env V1 region, beginning with SIV-PBj8. In addition, one of four SIV-PBj8 biologic clones had a 22-bp duplication in the LTR which is characteristic of SIV-PBj14. When virus mixtures containing different proportions of two SIV-PBj10 biologic clones with opposite phenotypes were tested, the SIV PBj14 phenotype was clearly dominant, since mixtures with as few as 10% of the viruses being SIV-PBj14-like exhibited all the properties of the lethal isolate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7884849 TI - Asymmetric replication in vitro from a human sequence element is dependent on adeno-associated virus Rep protein. AB - The DNA of human parvovirus adeno-associated virus type 2 (AAV) integrates preferentially into a defined region of human chromosome 19. Southern blots of genomic DNA from latently infected cell lines revealed that the provirus was not simply inserted into the cellular DNA. Both the proviral and adjoining cellular DNA organization indicated that integration occurred by a complex, coordinated process involving limited DNA replication and rearrangements. However, the mechanism for targeted integration has remained obscure. The two larger nonstructural proteins (Rep68 and Rep78) of AAV bind to a sequence element that is present in both the integration locus (P1) and the AAV inverted terminal repeat. This binding may be important for targeted integration. To investigate the mechanism of targeted integration, we tested the cloned integration site subfragment in a cell-free replication assay in the presence or absence of recombinant Rep proteins. Extensive, asymmetric replication of linear or open circular template DNA was dependent on the presence of P1 sequence and Rep protein. The activities of Rep on the cloned P1 element are analogous to activities on the AAV inverted terminal repeat. Replication apparently initiates from a 3'-OH generated by the sequence-specific nicking activity of Rep. This results in a covalent attachment between Rep and the 5'-thymidine of the nick. The complexity of proviral structures can be explained by the participation of limited DNA replication facilitated by Rep during integration. PMID- 7884850 TI - Cytomegalovirus-mediated induction of antisense mRNA expression to UL44 inhibits virus replication in an astrocytoma cell line: identification of an essential gene. AB - We have used an antisense RNA approach in the analysis of gene function in human cytomegalovirus (HCMV). An astrocytoma cell line (U373-MG) that is permissive for virus replication was permanently transfected with a construct bearing sequence from HCMV UL44 (coding for the major late DNA-binding protein, ppUL44, also known as pp52 or ICP36) in an antisense orientation and under the control of the immediate-early enhancer-promoter element. Upon HCMV infection at a high multiplicity, we found a marked reduction in UL44 protein products (the ICP36 family of proteins) in established cell transfectants and a strong inhibition of virus yield in infected-cell supernatants at two weeks postinfection, while herpes simplex virus replication was not affected. In infected cells, viral DNA replication was strongly inhibited. While gene products such as pUS22 and pUL32 were also inhibited, pUL123 and pUL82 accumulated in the infected cells over time. Our data suggest an essential role for the UL44 family of proteins in HCMV replication and represent a model of virus inhibition by virus-induced antisense RNA synthesis in genetically modified cells. PMID- 7884851 TI - Human immunodeficiency virus type 1 Vif- mutant particles from restrictive cells: role of Vif in correct particle assembly and infectivity. AB - Disruption of the vif gene of human immunodeficiency virus (HIV) type 1 affects virus infectivity to various degrees, depending on the T-cell line used. We have concentrated our studies on true phenotypic Vif- mutant particles produced from CEMx174 or H9 cells. In a single round of infection, Vif- virus is approximately 25 (from CEMx174 cells) to 100 (from H9 cells) times less infectious than wild type virus produced from these cells or than the Vif- mutant produced from HeLa cells. Vif- virions recovered from restrictive cells, but not from permissive cells, are abnormal both in terms of morphology and viral protein content. Notably, they contain much reduced quantities of envelope proteins and altered quantities of Gag and Pol proteins. Although wild-type and Vif- virions from restrictive cells contain similar quantities of viral RNA, no viral DNA synthesis was detectable after acute infection of target cells with phenotypically Vif- virions. To examine the possible role of Vif in viral entry, attempts were made to rescue the Vif- defect in H9 cells by pseudotyping Vif+ and Vif- HIV particles with amphotropic murine leukemia virus envelope. Vif- particles produced in the presence of HIV envelope could not be propagated when pseudotyped. In contrast, when only the murine leukemia virus envelope was present, significant propagation of Vif- HIV particles could be detected. These results demonstrate that Vif is required for proper assembly of the viral particle and for efficient HIV Env mediated infection of target cells. PMID- 7884852 TI - Peripheral blood mononuclear cells produce normal amounts of defective Vif- human immunodeficiency virus type 1 particles which are restricted for the preretrotranscription steps. AB - Previous studies have demonstrated the absence of viral replication of Vif- mutants in stimulated primary blood mononuclear cells (PBMC). Human immunodeficiency virus type 1 strain NDK Vif- mutants were propagated on the semipermissive CEM cell line, and the viral stock obtained was compared with the wild-type virus during a single cycle in PBMC. The Vif- virus was able to enter PBMC with the same efficiency as the wild type, as demonstrated by quantification of the strong-stop cDNA, and retrotranscription was observed for both viruses within 4 h postinfection. Using a PCR assay with an Alu-long terminal repeat pair of primers, we detected integration for both the wild-type and Vif- viruses. We then used qualitative and quantitative reverse transcription-mediated PCR techniques to study the steady-state level of intracellular and extracellular viral RNAs. All mRNA species were detected in PBMC infected with the wild-type virus or with the Vif- virus 36 h postinfection. Furthermore, quantification of viral RNA released from infected cells demonstrated similar levels of virus produced after a unique cycle of replication. However, the Vif- virus obtained after one replication cycle in PBMC was unable to initiate retrotranscription in permissive target cells. These data strongly suggest that the failure to infect target cells is due to a defect in the formation of the viral particle in PBMC. PMID- 7884853 TI - Virus-neutralizing antibodies of immunoglobulin G (IgG) but not of IgM or IgA isotypes can cure influenza virus pneumonia in SCID mice. AB - The ability of monoclonal antibodies (MAbs) to passively cure an influenza virus pneumonia in the absence of endogenous T- and B-cell responses was investigated by treating C.B-17 mice, homozygous for the severe combined immunodeficiency (SCID) mutation, with individual monoclonal antiviral antibodies 1 day after pulmonary infection with influenza virus PR8 [A/PR/8/34 (H1N1)]. Less than 10% of untreated SCID mice survived the infection. By contrast, 100% of infected SCID mice that had been treated with a single intraperitoneal inoculation of at least 175 micrograms of a pool of virus-neutralizing (VN+) antihemagglutinin (anti-HA) MAbs survived, even if antibody treatment was delayed up to 7 days after infection. The use of individual MAbs showed that recovery could be achieved by VN+ anti-HA MAbs of the immunoglobulin G1 (IgG1), IgG2a, IgG2b, and IgG3 isotypes but not by VN+ anti-HA MAbs of the IgA and IgM isotypes, even if the latter were used in a chronic treatment protocol to compensate for their shorter half-lives in vivo. Both IgA and IgM, although ineffective therapeutically, protected against infection when given prophylactically, i.e., before exposure to virus. An Fc gamma-specific effector mechanism was not an absolute requirement for antibody mediated recovery, as F(ab')2 preparations of IgGs could cure the disease, although with lesser efficacy, than intact IgG. An anti-M2 MAb of the IgG1 isotype, which was VN- but bound well to infected cells and inhibited virus growth in vitro, failed to cure. These observations are consistent with the idea that MAbs of the IgG isotype cure the disease by neutralizing all progeny virus until all productively infected host cells have died. VN+ MAbs of the IgA and IgM isotypes may be ineffective therapeutically because they do not have sufficient access to all tissue sites in which virus is produced during influenza virus pneumonia. PMID- 7884854 TI - An etoposide-induced block in vaccinia virus telomere resolution is dependent on the virus-encoded DNA ligase. AB - Etoposide, an inhibitor of the breakage-reunion reaction associated with cellular type II DNA topoisomerases, was shown to inhibit plaque formation of vaccinia virus. This drug had a major effect on the segregation of newly replicated DNA concatemers. Gene expression and the initiation and elongation phases of viral DNA replication were essentially unaffected. Pulsed-field gel electrophoresis of viral DNA replicated in the presence of etoposide revealed two major classes of DNA: the mature monomeric linear genome and DNA that failed to enter the gel (the relative proportions depending on the concentrations of drug). Restriction enzyme analysis showed a severe defect in telomere resolution. In addition, slowly migrating restriction fragments were suggestive of a general recombination defect. We have isolated several etoposide-resistant mutants and used marker rescue and DNA sequencing to localize the resistance-causing mutation to the amino terminus of the viral DNA ligase gene. Inactivation of the DNA ligase also resulted in an etoposide-resistant phenotype, but to a lesser extent. The telomere resolution and segregation defects were corrected both in the drug resistant mutants and in the DNA ligase knockout mutants. Reinsertion of wild type or mutant DNA ligase in the viral thymidine kinase locus confirmed the role of the viral DNA ligase in conferring sensitivity not only to etoposide but also to another topoisomerase II inhibitor, 4'-(9-acridinylamino) methanesulphon-m anisidide (mAMSA). The data suggest that the nonessential DNA ligase is involved in telomere resolution, possibly as part of a general recombinase. PMID- 7884855 TI - Changes in the viral mRNA expression pattern correlate with a rapid rate of CD4+ T-cell number decline in human immunodeficiency virus type 1-infected individuals. AB - The rate of disease progression varies considerably among human immunodeficiency virus type 1 (HIV-1)-infected individuals. Several cross-sectional studies have shown an association between the stage of HIV-1 disease and the viral burden or the relative levels of viral gene expression. To study the extent of HIV-1 transcription and replication and its correlations with disease progression, we quantified serial, longitudinal samples of blood cells from 10 HIV-1-infected individuals with markedly different rates of CD4+ T-cell number decline following seroconversion. After normalization for the input nucleic acid content, multiply spliced viral mRNA and unspliced viral RNA were quantified by competitive reverse transcription-PCR using oligonucleotide primers which flank the major tat/rev/nef splice junction and span an internal region of the gag open reading frame, respectively. Coamplification of internal cRNA template controls was used to normalize for variation in the efficiency of reverse transcription and in vitro enzymatic amplification. Similarly, proviral DNA was also quantified by competitive PCR performed within the linear range of amplification. Viral RNA was detected in the blood cells of each individual from all time points regardless of the rate of CD4+ T-cell decline. Unspliced genomic viral RNA rapidly increased in the blood cells from HIV-1-infected individuals who had a precipitously declining CD4+ T-cell number. In contrast, both unspliced and multiply spliced viral mRNAs remained relatively stable in the blood cells from HIV-1-infected individuals who have had a relatively benign clinical course. These data demonstrate that the extent of viral transcription and replication correlates with the rate of CD4+ T cell number decline and that quantifying intracellular viral RNA is of potential prognostic value. PMID- 7884856 TI - RNA secondary structure and binding sites for gag gene products in the 5' packaging signal of human immunodeficiency virus type 1. AB - The selective encapsidation of retroviral RNA requires sequences in the Gag protein, as well as a cis-acting RNA packaging signal (psi site) near the 5' end of the genomic transcript. Gag protein of human immunodeficiency virus type 1 (HIV-1) has recently been found to bind specifically to the HIV-1 psi element in vitro. Here we report studies aimed at mapping features within the genetically defined psi locus that are required for binding of HIV-1 Gag or of its processed nucleocapsid derivative. The full-length HIV-1 Gag (p55) and nucleocapsid (p15) sequences were expressed as glutathione S-transferase (GST) fusion proteins in Escherichia coli. In a gel shift assay containing excess competitor tRNA, affinity-purified GST-p15 and GST-p55 proteins bound to a 206-nucleotide psi RNA element spanning the major splice donor and gag start codons but did not bind to antisense psi transcripts. Quantitative filter-binding assays revealed that both GST-p55 and GST-p15 bound to this RNA sequence with identical affinities (apparent Kd congruent to 5 x 10(-8) M), indicating that all major determinants of psi binding affinity reside within the nucleocapsid portion of Gag. Chemical and RNase accessibility mapping, coupled with computerized sequence analysis, suggested a model for psi RNA structure comprising four independent stem-loops. Filter-binding studies revealed that RNAs corresponding to three of these hypothetical stem-loops can each function as a independent Gag binding site and that each is bound with approximately fourfold-lower apparent affinity than the full-length psi locus. Interaction of Gag with these regions is likely to play a major role in directing HIV-1 RNA encapsidation in vivo. PMID- 7884857 TI - Structural analysis of the principal immunodominant domain of the feline immunodeficiency virus transmembrane glycoprotein. AB - In the transmembrane envelope glycoprotein (TM) of lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV), two cysteine residues, conserved in most retroviruses, are thought to form a loop containing five to seven amino acids. These elements make up a B-cell epitope recognized by nearly 100% of sera from infected patients or animals, designated the principal immunodominant domain (PID). The PID amino acid sequences are highly conserved between isolates of the same lentivirus but are unrelated, except for the two cysteines, when divergent lentiviruses are compared. The aim of this study was to analyze the relationship between amino acid sequence in the PID and envelope function. We introduced two kinds of mutations in the PID of FIV: mutations which impeded the formation of a loop and mutations which substituted the sequence of FIV with the corresponding sequences from other lentiviruses, HIV-1, visna virus, and equine infectious anemia virus. We analyzed antibody recognition, processing, and fusogenic properties of the modified envelopes, using two methods of Env expression: a cell-free expression system and transfection of a feline fibroblast cell line with gag-pol-deleted FIV proviruses. Most mutations in the PID of FIV severely affected envelope processing and abolished syncytium formation. Only the chimeric envelope containing the HIV-1 PID sequence was correctly processed and maintained the capacity to induce syncytium formation, although less efficiently than the wild type envelope. We computed three-dimensional structural models of the PID, which were consistent with mutagenesis data and confirmed the similarity of FIV and HIV 1 PID structures, despite their divergence in amino acid sequence. Considering these results, we discussed the respective importance of selection exerted by functional requirements or host antibodies to explain the observed variations of the PIDs in lentiviruses. PMID- 7884858 TI - An immunoblot assay reveals that bacteriophage T4 thymidylate synthase and dihydrofolate reductase are not virion proteins. AB - Numerous reports describe the phage T4 enzymes thymidylate synthase and dihydrofolate reductase as structural components of the baseplate. However, Y. Wang and C. K. Mathews (J. Virol. 63:4736-4743, 1989) reported that antisera against the respective recombinant enzymes failed to neutralize phage infectivity, in contrast to previous results. Moreover, a deletion mutant lacking the genes for these two enzymes adsorbed normally to host cells. Since these findings tended to undermine the idea of the two enzymes as structural proteins, we developed a quantitative immunoblot assay to resolve the issue directly. Our results show that both enzymes are present only as minor contaminants (< 0.05 copy per phage) and as such cannot be bona fide structural proteins. PMID- 7884859 TI - Mutations within a putative cysteine loop of the transmembrane protein of an attenuated immunodeficiency-inducing feline leukemia virus variant inhibit envelope protein processing. AB - A replication-defective feline leukemia virus molecular clone, 61B, has been shown to cause immunodeficiency in cats and cytopathicity in T cells after a long latency period when coinfected with a minimally pathogenic helper virus (J. Overbaugh, E. A. Hoover, J. I. Mullins, D. P. W. Burns, L. Rudensey, S. L. Quackenbush, V. Stallard, and P. R. Donahue, Virology 188:558-569, 1992). The long-latency phenotype of 61B has been mapped to four mutations in the extracellular domain of the envelope transmembrane protein, and we report here that these mutations cause a defect in envelope protein processing. Immunoprecipitation analyses demonstrated that the 61B gp85 envelope precursor was produced but that further processing to generate the surface protein (SU/gp70) and the transmembrane protein (TM/p15E) did not occur. The 61B precursor was not expressed on the cell surface and appeared to be retained in the endoplasmic reticulum or Golgi apparatus. Two of the four 61B-specific amino acid changes are located within a putative cysteine loop in a region of TM that is conserved among retroviruses. Introduction of these two amino acid changes into a replication-competent highly cytopathic virus resulted in the production of noninfectious virus that exhibited an envelope-protein-processing defect. This analysis suggests that mutations in a conserved region within a putative cysteine loop affect retroviral envelope protein maturation and viral infectivity. PMID- 7884860 TI - Replication of macrophage-tropic and T-cell-tropic strains of human immunodeficiency virus type 1 is augmented by macrophage-endothelial cell contact. AB - Macrophages perform a central role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection and have been implicated as the cell type most prominent in the development of central nervous system impairment. In this study, we evaluated the effect of interaction between macrophages and endothelial cells on HIV-1 replication. Upregulation of HIV-1 replication was consistently observed in monocyte-derived macrophages (hereafter called macrophages) cocultured with either umbilical vein endothelial cells or brain microvascular endothelial cells. HIV-1 p24 antigen production of laboratory-adapted strains and patient-derived isolates was increased 2- to 1,000-fold in macrophage-endothelial cocultures, with little or no detectable replication in cultures containing endothelial cells only. The upregulation of HIV-1 in macrophage-endothelial cocultures was observed not only for viruses with the non-syncytium-inducing, macrophage-tropic phenotype but also for viruses previously characterized as syncytium inducing and T-cell tropic. In contrast, cocultures of macrophages with glioblastoma, astrocytoma, cortical neuronal, fibroblast, and placental cells failed to increase HIV-1 replication. Enhancement of HIV-1 replication in macrophage-endothelial cocultures required cell-to-cell contact; conditioned media from endothelial cells or macrophage-endothelial cocultures failed to augment HIV-1 replication in macrophages. Additionally, antibody to leukocyte function-associated antigen (LFA 1), a macrophage-endothelial cell adhesion molecule, inhibited the enhanced HIV-1 replication in macrophage-endothelial cell cocultures. Thus, these data indicate that macrophage-endothelial cell contact enhances HIV-1 replication in macrophages for both macrophage-tropic and previously characterized T-cell-tropic strains and that antibody against LFA-1 can block the necessary cell-to-cell interaction required for the observed upregulation. These findings may have important implications for understanding the ability of HIV-1 to replicate efficiently in tissue macrophages, including those in the brain and at the blood brain barrier. PMID- 7884861 TI - Detection of truncated virus particles in a persistent RNA virus infection in vivo. AB - Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus which causes devastating epizootics of trout and salmon fry in hatcheries around the world. In laboratory and field studies, epizootic survivors are negative for infectious virus by plaque assay at about 50 days postexposure. Survivors are considered virus free with no sequelae and, thus, are subsequently released into the wild. When adults return to spawn, infectious virus can again be isolated. Two hypotheses have been proposed to account for the source of virus in these adults. One hypothesis contends that virus in the epizootic survivors is cleared and that the adults are reinfected with IHNV from a secondary source during their migration upstream. The second hypothesis contends that IHNV persists in a subclinical or latent form and the virus is reactivated during the stress of spawning. Numerous studies have been carried out to test these hypotheses and, after 20 years, questions still remain regarding the maintenance of IHNV in salmonid fish populations. In the study reported here, IHNV-specific lesions in the hematopoietic tissues of rainbow trout survivors, reared in specific-pathogen free water, were detected 1 year after the epizootic. The fish did not produce infectious virus. The presence of viral protein detected by immunohistochemistry, in viral RNA by PCR amplification, and in IHNV-truncated particles by immunogold electron microscopy confirmed the presence of IHNV in the survivors and provided the first evidence for subclinical persistence of virus in the tissues of IHNV survivors. PMID- 7884862 TI - Characterization of a human immunodeficiency virus type 1 variant with reduced sensitivity to an aminodiol protease inhibitor. AB - Development of viral resistance to the aminodiol human immunodeficiency virus (HIV) protease inhibitor BMS 186,318 was studied by serial passage of HIV type 1 RF in MT-2 cells in the presence of increasing concentrations of compound. After 11 passages, an HIV variant that showed a 15-fold increase in 50% effective dose emerged. This HIV variant displays low-level cross-resistance to the C2 symmetric inhibitor A-77003 but remains sensitive to the protease inhibitors Ro 31-8959 and SC52151. Genetic analysis of the protease gene from a drug-resistant variant revealed an Ala-to-Thr change at amino acid residue 71 (A71T) and a Val-to-Ala change at residue 82 (V82A). To determine the effects of these mutations on protease and virus drug susceptibility, recombinant protease and proviral HIV type 1 clones containing the single mutations A71T and V82A or double mutation A71T/V82A were constructed. Subsequent drug sensitivity assays on the mutant proteases and viruses indicated that the V82A substitution was responsible for most of the resistance observed. Further genotypic analysis of the protease genes from earlier passages of virus indicated that the A71T mutation emerged prior to the V82A change. Finally, the level of resistance did not increase following continued passage in increasing concentrations of drug, and the resistant virus retained its drug susceptibility phenotype 34 days after drug withdrawal. PMID- 7884863 TI - Antiviral protection by vesicular stomatitis virus-specific antibodies in alpha/beta interferon receptor-deficient mice. AB - The role of innate, alpha/beta interferon (IFN-alpha/beta)-dependent protection versus specific antibody-mediated protection against vesicular stomatitis virus (VSV) was evaluated in IFN-alpha/beta receptor-deficient mice (IFN-alpha/beta R0/0 mice). VSV is a close relative to rabies virus that causes neurological disease in mice. In contrast to normal mice, IFN-alpha/beta R0/0 mice were highly susceptible to infection with VSV because of ubiquitous high viral replication. Adoptive transfer experiments showed that neutralizing antibodies against the glycoprotein of VSV (VSV-G) protected these mice efficiently against systemic infection and against peripheral subcutaneous infection but protected only to a limited degree against intranasal infection with VSV. In contrast, VSV-specific T cells or antibodies specific for the nucleoprotein of VSV (VSV-N) were unable to protect IFN-alpha/beta R0/0 mice against VSV. These results demonstrate that mice are extremely sensitive to VSV if IFN-alpha/beta is not functional and that under these conditions, neutralizing antibody responses mediate efficient protection, but apparently only against extraneuronal infection. PMID- 7884864 TI - Restriction of human immunodeficiency virus type 1 production in a human astrocytoma cell line is associated with a cellular block in Rev function. AB - Chronically human immunodeficiency virus type 1 (HIV-1) strain IIIB-infected human TH4-7-5 astrocytoma cells show low-level virus production. Cocultivation of TH4-7-5 cells with myelomonocytic cells led to active virus production in these target cells after a lag period, indicating cell-determined restriction of virus replication in the glial cells. HIV-1 transcript patterns of TH4-7-5 cells contained only a small proportion of Rev-dependent mRNA species, mimicking a Rev negative phenotype despite the presence of rev mRNAs and protein. Sequencing of the single provirus integrated in TH4-7-5 cells demonstrated that the rev gene and the Rev-responsive element are intact. These results suggested inhibited function of the Rev-regulatory unit in these astrocytoma cells. Transfection of TH4-7-5 cells with a Rev expression plasmid resulted in weak or no induction of proviral p24gag antigen levels compared with the dramatic increase observed in Rev-permissive HeLa cells. Immunofluorescence analysis of TH4-7-5 cells transfected with a rev-expressing plasmid revealed prominent cytoplasmic and nuclear-nucleolar localization of Rev, in contrast to the predominant nuclear nucleolar localization pattern of Rev in HeLa cells. We conclude that restriction of virus production in TH4-7-5 cells is at least partially due to a block in Rev dependent posttranscriptional regulation of HIV expression. PMID- 7884865 TI - LMP-1 activates NF-kappa B by targeting the inhibitory molecule I kappa B alpha. AB - LMP-1, an Epstein-Barr virus membrane protein expressed during latent infection, has oncogenic properties, as judged from its ability to transform B lymphocytes and rodent fibroblasts. LMP-1 induces the expression of bcl2, an oncogene which protects cells from apoptosis, as well as of genes encoding other proteins involved in cell regulation and growth control. The mechanisms by which LMP-1 upregulates these proteins is unknown, but it is plausible that LMP-1 modifies signal transduction pathways that result in the activation of one or more transcription factors that ultimately regulate transcription of oncogenic genes. NF-kappa B, a transcription factor controlling the expression of genes involved in cell activation and growth control, has been shown to be activated by LMP-1. The mechanism(s) regulating this activation remains unknown. Our data indicate that increased NF-kappa B DNA binding and functional activity are present in B lymphoid cells stably or transiently expressing LMP-1. I kappa B alpha is selectively modified in LMP-1-expressing B cells. A phosphorylated form of I kappa B alpha and increased protein turnover-degradation correlate with increased NF-kappa B nuclear translocation. This results in increased transcription of NF kappa B-dependent-genes, including those encoding p105 and I kappa B alpha (MAD3). These results indicate that LMP-1 activates NF-kappa B in B-cell lines by targeting I kappa B alpha. Identification of the pathways activated by LMP-1 to result in posttranslational modifications of I kappa B alpha will aid in determining the role of this virus-host cell protein interaction in Epstein-Barr virus-mediated oncogenesis. PMID- 7884866 TI - Secondary structure model of the Mason-Pfizer monkey virus 5' leader sequence: identification of a structural motif common to a variety of retroviruses. AB - A stable secondary structure model is presented for the region 3' of the primer binding site to 130 bases into the gag sequence of the prototype type D retrovirus Mason-Pfizer monkey virus. Using biochemical probing of RNA from this region in association with free energy minimization, we have identified a stem loop structure in the region, which from other studies has been shown to be important for genomic RNA encapsidation. The structure involves a highly stable stem of five G-C pairs terminating in a heptaloop. Comparison of the Mason-Pfizer monkey virus structure with one predicted for squirrel monkey retrovirus demonstrates an identical stem and a common ACC motif in the loop. Free energy studies of the secondary structure of the 5' regions of eight other retroviruses predict stem loops which have similar GAYC motifs. We believe this may represent a common structural and sequence motif which among other functions may be involved in genomic RNA packaging in these viruses. PMID- 7884867 TI - Human cytomegalovirus (HCMV) immediate-early enhancer/promoter specificity during embryogenesis defines target tissues of congenital HCMV infection. AB - Congenital human cytomegalovirus (HCMV) infection is a common cause of deafness and neurological disabilities. Many aspects of this prenatal infection, including which cell types are infected and how infection proceeds, are poorly understood. Transcription of HCMV immediate-early (IE) genes is required for expression of all other HCMV genes and is dependent on host cell transcription factors. Cell type-specific differences in levels of IE transcription are believed to underlie differences in infection permissivity. However, DNA transfection experiments have paradoxically suggested that the HCMV major IE enhancer/promoter is a broadly active transcriptional element with little cell type specificity. In contrast, we show here that expression of a lacZ gene driven by the HCMV major IE enhancer/promoter -524 to +13 segment is restricted in transgenic mouse embryos to sites that correlate with known sites of congenital HCMV infection in human fetuses. This finding suggests that the IE enhancer/promoter is a major determinant of HCMV infection sites in humans and that transcription factors responsible for its regulation are cell type-specifically conserved between humans and mice. The lacZ expression patterns of these transgenic embryos yield insight into congenital HCMV pathogenesis by providing a spatiotemporal map of the sets of vascular, neural, and epithelial cells that are likely targets of infection. These transgenic mice may constitute a useful model system for investigating IE enhancer/promoter regulation in vivo and for identifying factors that modulate active and latent HCMV infections in humans. PMID- 7884868 TI - An internal ribosomal entry mechanism promotes translation of murine leukemia virus gag polyprotein precursors. AB - The genomic retroviral RNA is the messenger for the translation of the gag and pol genes encoding the precursors to the major structural proteins and enzymes, respectively, of the virion core. The long 5' untranslated region, the leader, is formed of independent well-structured domains involved in key steps of the viral life cycle such as the initiation of proviral DNA synthesis, genomic RNA dimerization and packaging, and the initiation of gag translation. These functional features and the presence of stable secondary structures between the cap and the gag initiation codon suggested that translation initiation of gag might proceed through a mechanism different from the canonical ribosome scanning process. Interestingly enough, murine leukemia viruses code also for a glycosylated gag precursor, named glyco-gag, initiated at a CUG codon upstream and in the same open reading frame as the AUGgag. We have investigated the translation initiation of gag and glyco-gag precursors of Friend murine leukemia virus (F-MLV) in the rabbit reticulocyte lysate system and in murine cells. Through site-directed mutagenesis of gag and glyco-gag initiation codons, we show that initiation of gag and glyco-gag synthesis does not utilize the classical ribosome scanning. When poliovirus protease 2A is coexpressed in murine cells, expression of MLV-lacZ RNA is not modified, indicating that translation initiation of MLV gag precursors is a cap-independent mechanism. In addition, the F-MLV leader was inserted between two genes in a dicistronic neo-MLV-lacZ mRNA, and its ability to promote expression was examined in vitro and in vivo. Results obtained demonstrate that an internal ribosome entry mechanism promotes translation of F-MLV gag precursors. This finding led us to construct a new dicistronic retroviral vector in which the F-MLV leader can promote both packaging of recombinant genomic RNA and expression of the 3' gene. PMID- 7884869 TI - Interactions between human immunodeficiency virus type 1 and human cytomegalovirus in human term syncytiotrophoblast cells coinfected with both viruses. AB - Human cytomegalovirus (HCMV) and human immunodeficiency virus type 1 (HIV-1) may interact in the pathogenesis of AIDS. The placental syncytiotrophoblast layer serves as the first line of defense of the fetus against viruses. We analyzed the patterns of replication of HIV-1 and HCMV in singly an dually infected human term syncytiotrophoblast cells cultured in vitro. Syncytiotrophoblast cells exhibited restricted permissiveness for HIV-1, while HCMV replication was restricted at the level of immediate-early and early gene products in the singly infected cells. We found that the syncytiotrophoblasts as an overlapping cell population could be coinfected with HIV-1 and HCMV. HIV-1 replication was markedly upregulated by previous or simultaneous infection of the cells with HCMV, whereas prior HIV-1 infection of the cells converted HCMV infection from a nonpermissive to a permissive one. No simultaneous enhancement of HCMV and HIV-1 expression was observed in the dually infected cell cultures. Major immediate-early proteins of HCMV were necessary for enhancement of HIV-1 replication, and interleukin-6 production induced by HCMV and further increased by replicating HIV-1 synergized with these proteins to produce this effect. Permissive replication cycle of HCMV was induced by the HIV-1 tat gene product. We were unable to detect HIV-1 (HCMV) or HCMV (HIV-1) pseudotypes in supernatant fluids from dually infected cell cultures. Our results suggest that interactions between HIV-1 and HCMV in coinfected syncytiotrophoblast cells may contribute to the transplacental transmission of both viruses. PMID- 7884870 TI - Mediation of human immunodeficiency virus type 1 binding by interaction of cell surface heparan sulfate proteoglycans with the V3 region of envelope gp120-gp41. AB - The mechanism of heparan sulfate (HS)-mediated human immunodeficiency virus type 1 (HIV-1) binding to and infection of T cells was investigated with a clone (H9h) of the T-cell line H9 selected on the basis of its high level of cell surface CD4 expression. Semiquantitative PCR analysis revealed that enzymatic removal of cell surface HS by heparitinase resulted in a reduction of the amount of HIV-1 DNA present in H9h cells 4 h after exposure to virus. Assays of the binding of recombinant envelope proteins to H9h cells demonstrated a structural requirement for an oligomeric form of gp120/gp41 for HS-dependent binding to the cell surface. The ability of the HIV-1 envelope to bind simultaneously to HS and CD4 was shown by immunoprecipitation of HS with either antienvelope or anti-CD4 antibodies from 35SO4(2-)-labeled H9h cells that had been incubated with soluble gp140. Soluble HS blocked the binding of monoclonal antibodies that recognize the V3 and C4 domains of the envelope protein to the surface of H9 cells chronically infected with HIV-1IIIB. The V3 domain was shown to be the major site of envelope HS interaction by examining the effects of both antienvelope monoclonal antibodies and heparitinase on the binding of soluble gp140 to H9h cells. PMID- 7884871 TI - A fully 5'-CG-3' but not a 5'-CCGG-3' methylated late frog virus 3 promoter retains activity. AB - Several lines of evidence demonstrate that the DNA of the iridovirus frog virus 3 (FV3) is methylated in all 5'-CG-3' sequences both in virion DNA and in the intracellular viral DNA at late times after infection. The 5-methyldeoxycytidine residues in this viral DNA occur exclusively in 5'-CG-3' dinucleotide positions. We have cloned and determined the nucleotide sequence of the L1140 gene and its promoter from FV3 DNA. The gene encodes a 40-kDa protein. The results of transcriptional pattern analyses for this gene in fathead minnow fish cells document that this gene is transcribed exclusively late after FV3 infection. The L1140 gene and its promoter are fully methylated at late times after infection. We have been interested in resolving the apparent paradox that the methylated L1140 promoter is methylated and active late in FV3-infected cells. Of course, the possibility cannot be excluded that one or a few 5'-CG-3' sequences outside restriction endonuclease sites escaped de novo methylation after FV3 DNA replication. We have devised a construct that places the chloramphenicol acetyltransferase gene under the control of the L1140 promoter. Upon transfection, this construct exhibits activity only in FV3-infected BHK-21 hamster cells, not in uninfected BHK-21 cells. The fully 5'-CG-3' or 5'-GCGC-3' (HhaI) methylated, HpaII-mock-methylated, or unmethylated L1140 promoter chloramphenicol acetyltransferase gene construct is active in FV3-infected BHK-21 cells, whereas the same construct 5'-CCGG-3' (HpaII) methylated has lost activity. Apparently, complete methylation of the late L1140 promoter in FV3 DNA is compatible with activity. However, a very specific 5'-CCGG-3' methylation pattern that does not naturally occur in authentic FV3 DNA in infected cells abrogates promoter function. These results further support the notion that very specific patterns of methylation are required to inhibit or inactivate viral promoters. PMID- 7884872 TI - Physical association of moesin and CD46 as a receptor complex for measles virus. AB - Recently, two cellular membrane proteins, the membrane cofactor protein CD46 and the membrane-organizing external spike protein, moesin, have been identified to be functionally associated with measles virus (MV) infectivity of cells. We investigated the functional consequences of binding of monoclonal antibodies to both molecules individually and combined on MV attachment, fusion, and plaque formation and the putative direct physical interaction of moesin and CD46. We found that antibodies to moesin or CD46 separately inhibited MV-cell interactions to a high percentage in the plaque test, by approximately 85 and 75%, respectively. The inhibition by combinations of antibodies was additive at low concentrations and complete at high concentrations. This indicates that similar sites of interaction were blocked by steric hindrance. Furthermore, antimoesin antibodies blocked the infection of CD46-negative mouse cell lines with MV. Chemical cross-linking of cell surface proteins indicated the close proximity of CD46 and moesin in the membrane of human cells, and coimmunoprecipitation of moesin with CD46 suggested their physical interaction. Immunohistochemically by electron microscopy, CD46 and moesin were found to be localized at sites of the cellular membrane where MV particles adsorbed. These data support a model of direct interaction of CD46 and moesin in the cellular membrane and suggest that this complex is functionally involved in the uptake of MV into cells. PMID- 7884873 TI - In vivo deletion analysis of the herpes simplex virus type 1 latency-associated transcript promoter. AB - During herpes simplex virus latency, transcripts accumulate from a single transcription unit of the viral genome. The promoter for these latency-associated transcripts (LAT) has been located, and a number of studies have documented the specific regions of this promoter which are important in transient assays of neuronal cells in culture. To examine the regulation of this promoter from the viral genome, both in vitro and in vivo, a series of seven promoter deletion viruses which drive the expression of the reporter gene beta-galactosidase was constructed. Rabbit skin cells were infected in cell culture with viruses bearing each promoter mutation, and the LAT promoter activity was compared with that obtained by infecting two neuronal cell lines, ND7 cells and C1300 neuroblastoma cells. Mouse dorsal root ganglia were also infected with these recombinant viruses by footpad inoculations, and beta-galactosidase activity was measured. Infected neuronal cells lines and dorsal root ganglia exhibit much more LAT promoter activity than infected rabbit skin cells, suggesting that the region upstream of -250 may contain one or several neuronal specific DNA-binding sites. However, a comparison of LAT promoter activities within the deletion series revealed many differences between neurons of the dorsal root ganglia infected in vivo and the two neuronal cell lines infected in vitro. These results suggest that neurons may vary extensively in the quantity or kind of transcription factors they contain. PMID- 7884874 TI - A vaccine-elicited, single viral epitope-specific cytotoxic T lymphocyte response does not protect against intravenous, cell-free simian immunodeficiency virus challenge. AB - Protection against simian immunodeficiency virus (SIV) challenge was assessed in rhesus monkeys with a vaccine-elicited, single SIV epitope-specific cytotoxic T lymphocyte (CTL) response in the absence of SIV-specific antibody. Strategies were first explored for eliciting an optimal SIV Gag epitope-specific CTL response. These studies were performed in rhesus monkeys expressing the major histocompatibility complex (MHC) class I gene Mamu-A*01, a haplotype associated with a predominant SIV CTL epitope mapped to residues 182 to 190 of the Gag protein (p11C). We demonstrated that a combined modality immunization strategy using a recombinant Mycobacterium bovis BCG-SIV Gag construct for priming, and peptide formulated in liposome for boosting, elicited a greater p11C-specific CTL response than did a single immunization with peptide-liposome alone. Vaccinated and control monkeys were then challenged with cell-free SIVmne by an intravenous route of inoculation. Despite a vigorous p11C-specific CTL response at the time of virus inoculation, all monkeys became infected with SIV. gag gene sequencing of the virus isolated from these monkeys demonstrated that the established viruses had no mutations in the p11C-coding region. Thus, the preexisting CTL response did not select for a viral variant that might escape T-cell immune recognition. These studies demonstrate that a potent SIV-specific CTL response can be elicited by combining live vector and peptide vaccine modalities. However, a single SIV Gag epitope-specific CTL response in the absence of SIV-specific antibody did not provide protection against a cell-free, intravenous SIV challenge. PMID- 7884875 TI - Similarity in env and gag genes between genomic RNAs of human immunodeficiency virus type 1 (HIV-1) from mother and infant is unrelated to time of HIV-1 RNA positivity in the child. AB - Variation in the env (V3 region) and gag (p17 region) genes of genomic RNA of human immunodeficiency virus type 1 was studied in three mother-child pairs. One infant was human immunodeficiency virus type 1 RNA positive at birth (pair 114), one became positive 6 weeks after birth (pair 127), and one became positive 30 months after birth (pair 564). The first two children were born to seropositive mothers, and the last child was infected by breast-feeding following seroconversion of the mother after delivery. In both V3 and p17gag, intrasample variability was much higher in the maternal samples, including the first seropositive sample of the seroconverted mother, than in the infants' samples. Variability was less in p17gag than in V3, except in the postnatally infected child. In all three cases, infection of the child was established by variants representing a minority of the cell-free virus population in the maternal samples. For the two infants born to seropositive mothers, V3 sequences were more similar to the sequence populations of maternal samples collected during pregnancy than to those of samples collected at delivery or thereafter. However, in pair 114 a V3 variant identical to the child's virus was also detected in the sample collected at delivery. In contrast to the V3 region, p17gag sequences of maternal samples of the first trimester of pregnancy and at delivery had comparable resemblance to the child's sequences in pair 114, while in pair 127, similarity to sequences of the sample collected at delivery was higher than that to sequences of the sample from early in pregnancy. In the last pair, V3 and p17gag sequences from a maternal sample collected 18 months prior to the first RNA-positive sample of the child resembled the infant's sequences as much as the sample collected close to the presumed time of infection. Taken together, the evolutionary characteristics for genomic RNA env and gag genes did not point to a particular time of mother-to-child transmission. PMID- 7884876 TI - Requirement for vacuolar proton-ATPase activity during entry of influenza virus into cells. AB - The role that endosomal acidification plays during influenza virus entry into MDCK cells has been analyzed by using the macrolide antibiotics bafilomycin A1 and concanamycin A as selective inhibitors of vacuolar proton-ATPase (v [H+]ATPase), the enzyme responsible for the acidification of endosomes. Bafilomycin A1 and concanamycin A, present at the low concentrations of 5 x 10( 7) and 5 x 10(-9) M, respectively, prevented the entry of influenza virus into cells when added during the first minutes of infection. Attachment of virion particles to the cell surface was not the target for the action of bafilomycin A1. N,N'-Dicyclohexylcarbodiimide, a nonspecific inhibitor of proton-ATPases, also blocked virus entry, whereas elaiophylin, an inhibitor of the plasma-proton ATPase, had no effect. The inhibitory actions of bafilomycin A1 and concanamycin A were tested in culture medium at different pHs. Both antibiotics powerfully prevented influenza virus infection when the virus was added under low-pH conditions. This inhibition was reduced if the virus was bound to cells at 4 degrees C prior to the addition of warm low-pH medium. Moreover, incubation of cells at acidic pH potently blocked influenza virus infection, even in the absence of antibiotics. These results indicate that a pH gradient, rather than low pH, is necessary for efficient entry of influenza virus into cells. PMID- 7884877 TI - Two murine coronavirus genes suffice for viral RNA synthesis. AB - We identified two mouse hepatitis virus (MHV) genes that suffice for MHV RNA synthesis by using an MHV-JHM-derived defective interfering (DI) RNA, DIssA. DIssA is a naturally occurring self-replicating DI RNA with nearly intact genes 1 and 7. DIssA interferes with most MHV-JHM-specific RNA synthesis, except for synthesis of mRNA 7, which encodes N protein; mRNA 7 synthesis is not inhibited by DIssA. Coinfection of MHV-JHM containing DIssA DI particles and an MHV-A59 RNA temperature-sensitive mutant followed by subsequent passage of virus at the permissive temperature resulted in elimination of most of the MHV-JHM helper virus. Analysis of intracellular RNAs at the nonpermissive temperature demonstrated efficient synthesis of DIssA and mRNA 7 but not of the helper virus mRNAs. Oligonucleotide fingerprinting analysis demonstrated that the structure of mRNA 7 was MHV-JHM specific and therefore must have been synthesized from the DIssA template RNA. Sequence analysis revealed that DIssA lacks a slightly heterogeneous sequence, which is found in wild-type MHV from the 3' one-third of gene 2-1 to the 3' end of gene 6. Northern (RNA) blot analysis of intracellular RNA species and virus-specific protein analysis confirmed the sequence data. Replication and transcription of another MHV DI RNA were supported in DIssA replicating cells. Because the products of genes 2 and 2-1 are not essential for MHV replication, we concluded that expression of gene 1 proteins and N protein was sufficient for MHV RNA replication and transcription. PMID- 7884878 TI - Halophage HF2: genome organization and replication strategy. AB - Halophage HF2 is a lytic, broad-host-range bacteriophage of the extremely halophilic domain Archaea. It has a 79.7-kb double-stranded DNA genome which is linear, contains no modified nucleotides, and is not susceptible to cleavage by many type II restriction endonucleases. This insensitivity is attributed to selection against palindromic restriction sites, a commonly observed feature of broad-host-range phages. Interestingly, enzymes that did cut the genome recognized AT-rich sites, and five such enzymes, DraI, AseI, HpaI, HindIII, and SspI, were used to construct a physical map of the genome. Southern hybridization experiments used to order fragments on the map indicated homologies between the phage termini, and subsequent sequence analysis showed that HF2 possessed 306-bp direct terminal repeats. The presence of such repeats suggested replication through concatameric intermediates, and this was confirmed by analysis of the state of the phage genome in infected cells. This is a replication strategy adopted by many well-studied bacterial phages, for example T3 and T7. Other similarities between the terminal repeats of T3 or T7 and HF2 include a putative nick site at the repeat border and a series of short imperfect repeats. These observations suggest a long evolutionary history for concatamer-based strategies of phage replication, possibly predating the divergence of Archaea/Eucarya and Bacteria, or alternatively, indicate possible lateral transfer of phage genes or modules between the domains Archaea and Bacteria. PMID- 7884879 TI - Identification of a novel E1A response element in the mouse c-fos promoter. AB - Transcriptional activation of the c-fos gene in mouse S49 cells by the adenovirus 243-amino-acid E1A protein depends on domains of E1A that are also required for transformation and that bind the cellular protein p300. Activation additionally depends on stimulation of endogenous cyclic AMP (cAMP)-dependent protein kinase by analogs or inducers of cAMP. Transient transfection assays were used to analyze the c-fos promoter for sequences that confer responsiveness to E1A. Linker substitution and point mutants revealed that transcriptional activation by E1A depended on a cAMP response element (CRE) located at -67 relative to the start site of transcription and a neighboring binding site for transcription factor YY1 located at -54. A 22-bp sequence containing the -67 CRE and the -54 YY1 site was sufficient to confer responsiveness to a minimal E1B promoter and was termed the c-fos E1A response element (ERE). Function of the c-fos ERE depended on both the CRE and the YY1 site, since mutation of either site resulted in a loss of responsiveness to E1A. These results imply a specific functional interaction between CRE-binding proteins, transcription factor YY1, and E1A in the regulation of the c-fos gene. PMID- 7884880 TI - Bovine papillomavirus E1 protein binds specifically DNA polymerase alpha but not replication protein A. AB - Extracts prepared from either mouse cells or monkey cells were examined for the ability to support in vitro bovine papillomavirus type 1 (BPV1) DNA replication, and they were used in parallel as a source of host replication proteins for affinity chromatography. DNA synthesis exhibited an absolute requirement for BPV1 E1 protein. In contrast to previous observations, we found that low levels of E1 were highly efficient in initiating DNA replication in the absence of the BPV1 transcription factor E2. Surprisingly, COS-1 cell extract allowed a high rate of BPV1 DNA replication, supporting an efficient production of mature circular DNA molecules, whereas in mouse cell extracts, the replication products mostly consisted of replicative intermediates. Submitting the extracts to affinity chromatography allowed specific binding of DNA polymerase alpha-primase to E1 protein, up to a total depletion of the extract, regardless of the origin of the cell extract. Furthermore, replication protein A was not retained on E1 affinity columns, even when E2 was complexed with E1. These data confirm that the interactions between E1 and DNA polymerase alpha-primase do not exhibit cell-type specificity, as had already been suggested by data from in vivo and in vitro replication assays, but they imply that other cellular proteins may affect the level of E1-dependent replication. PMID- 7884881 TI - Intraspecific phylogenetics: support for dental transmission of human immunodeficiency virus. AB - A new method to estimate within-species gene genealogies was used to establish linkages among individuals associated with the Florida dental human immunodeficiency virus transmission case. Phylogenetic relationships were estimated from 103 nucleotide sequences from the V3 region of the env gene representing the Florida dentist, eight of his seropositive patients, and many local controls. The cladogram estimation procedure supports linkages among individuals within the previously described dental clade, whereas local controls and other patients form independent networks or are outliers in the main network, indicating more distant evolutionary relationships. A nested statistical analysis also indicates significant cohesion of the dental clade group. PMID- 7884882 TI - Sequence requirements for encapsidation of deletion mutants and chimeras of human immunodeficiency virus type 1 Gag precursor into retrovirus-like particles. AB - Interacting domains in human immunodeficiency virus type 1 (HIV-1) Gag precursor (Pr55gag) expressed in recombinant baculovirus-infected cells were investigated by three different methods: (i) trans rescue and coencapsidation of C-terminal deletion (amber) Gag mutants and Gag chimeras into retrovirus-like particles in complementation experiments with HIV-1 wild-type (WT) Pr55gag, (ii) Gag-Gag interactions in vitro in Gag ligand affinity blotting assays, and (iii) quantitative immunoelectron microscopy of retrovirus-like Gag particles, using a panel of monoclonal antibodies to probe the epitope accessibility of encapsidated HIV-1 WT Pr55gag. Four discrete regions, within residues 210 to 241, 277 to 306 (major homology region), and 307 to 333 in the capsid (CA) protein and residues 358 to 374 at the CA-spacer peptide 2 (sp2) junction, were found to have a significant influence on Gag trans-packaging efficiency. A fifth region, within residues 375 to 426, overlapping the sp2-nucleocapsid (NC) protein junction and most of the NC, seemed to be essential for stable inter-Gag binding in vitro. The coincidence of the two regions from 358 to 374 and 375 to 426 with an immunologically silent domain in WT Gag particles suggested that they could participate in direct Gag interactions. PMID- 7884883 TI - Progression to AIDS in the absence of a gene for vpr or vpx. AB - Rhesus monkeys (Macaca mulatta) were experimentally infected with strains of simian immunodeficiency virus (SIV) derived from SIVmac239 lacking vpr, vpx, or both vpr and vpx genes. These auxiliary genes are not required for virus replication in cultured cells but are consistently conserved within the SIVmac/human immunodeficiency virus type 2/SIVsm group of primate lentiviruses. All four rhesus monkeys infected with the vpr deletion mutant showed an early spike in plasma antigenemia, maintained high virus burdens, exhibited declines in CD4+ lymphocyte concentrations, and had significant changes in lymph node morphology, and two have died to date with AIDS. The behavior of the vpr deletion mutant was indistinguishable from that of the parental, wild-type virus. Rhesus monkeys infected with the vpx deletion mutant showed lower levels of plasma antigenemia, lower virus burdens, and delayed declines in CD4+ lymphocyte concentrations but nonetheless progressed with AIDS to a terminal stage. The vpr+vpx double mutant was severely attenuated, with much lower virus burdens and no evidence of disease progression. These and other results indicate that vpr provides only a slight facilitating advantage for wild-type SIVmac replication in vivo. Thus, progression to AIDS and death can occur in the absence of a gene for vpr or vpx. PMID- 7884884 TI - Inhibition of apoptosis in human immunodeficiency virus-infected cells enhances virus production and facilitates persistent infection. AB - Apoptosis is one of several mechanisms by which human immunodeficiency virus type 1 (HIV-1) exerts its cytopathic effects. CD4+ Jurkat T-cell lines overexpressing the adenovirus E1B 19K protein, a potent inhibitor of apoptosis, were used to examine the consequences of inhibition of apoptosis during acute and chronic HIV 1 infections. E1B 19K protein expression inhibited HIV-induced apoptosis, enhanced virus production, and established high levels of persistent viral infection. One E1B 19K-expressing line appeared to undergo HIV-induced death via a nonapoptotic mechanism, illustrating that HIV infection results in lymphocyte depletion through multiple pathways. Increased virus production associated with sustained cell viability suggests that therapeutic approaches involving inhibition of HIV-induced programmed cell death may be problematic. PMID- 7884885 TI - Increased adhesion as a mechanism of antibody-dependent and antibody-independent complement-mediated enhancement of human immunodeficiency virus infection. AB - Enhancement of human immunodeficiency virus (HIV) infection by complement alone or in conjunction with antibodies was studied experimentally and theoretically. Experimental studies showed that while HIV-positive sera neutralize HIV infection, the addition of fresh complement abrogated neutralization and could even cause enhancement. Enhancement was blocked by anti-complement receptor 2 antibodies, and infection under enhancing conditions could be blocked by soluble CD4. Antibody-dependent complement-mediated enhancement (C'ADE) was dependent on the alternative complement activation pathway, as factor B-deficient serum could enhance only after the addition of factor B. The observed enhancement was also antibody dependent, since the addition of antibodies increased the level of enhancement. Under C'ADE conditions, infection reached a plateau within 5 min and was not caused by activation of cells by factors in the human serum. On the contrary, preincubation of cells with complement decreased the level of enhancement. A theoretical model of HIV infection in vitro which exhibited similar enhancement in an antibody- and complement concentration-dependent way was developed. Model studies indicated that the enhanced infection process could be explained by the fact that virions, because of complement deposition on the surface, bind more efficiently to cells. The model also indicated that the saturation of the enhanced infection process seen after a few minutes could be caused by saturation of the complement receptors. The effect of neutralizing antibodies can thus be overcome by the enhancing effect of complement that facilitates the contact between gp120 and CD4. These studies demonstrate that the main features of the complement-dependent enhancement phenomenon can be understood in terms of a simple mathematical model. PMID- 7884886 TI - Chimeras of receptors for gibbon ape leukemia virus/feline leukemia virus B and amphotropic murine leukemia virus reveal different modes of receptor recognition by retrovirus. AB - Glvr1 encodes the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related gene Glvr2 encodes the human receptor for amphotropic murine leukemia viruses (A-MLVs). The two proteins are 62% identical in their amino acid sequences and are predicted to have 10 transmembrane domains and five extracellular loops. A stretch of nine amino acids (region A) in the predicted fourth extracellular loop was previously shown to be critical for the function of Glvr1 as receptor for GALV and FeLV-B. Glvr1 and -2 show clusters of amino acid differences in several of their predicted extracellular loops, with the highest degree of divergence in region A. Chimeras were made between the two genes to further investigate the role of Glvr1 region A in defining receptor specificity for GALV and FeLV-B and to map which regions of Glvr2 control receptor specificity for A-MLVs. Region A from Glvr1 was sufficient to confer receptor specificity for GALV upon Glvr2, with the same chimera failing to act as a receptor for FeLV-B. However, introduction of additional N- or C terminal Glvr1-encoding sequences in addition to Glvr1 region A-encoding sequences resulted in functional FeLV-B receptors. Therefore, FeLV-B is dependent on Glvr1 sequences outside region A for infectivity. The receptor specificity of Glvr2 for A-MLV could not be mapped to a single critical region; rather, N terminal as well as C-terminal Glvr2-encoding sequences could confer specificity for A-MLV infection upon Glvr1. Surprisingly, though GALV/FeLV-B and A-MLV belong to different interference groups, some chimeras functioned as receptors for all three viruses. PMID- 7884887 TI - Chimeras from a human rhinovirus 14-human immunodeficiency virus type 1 (HIV-1) V3 loop seroprevalence library induce neutralizing responses against HIV-1. AB - A chimeric virus library was designed whereby sequences corresponding to the V3 loop of human immunodeficiency virus type 1 (HIV-1) were presented on the surface of human rhinovirus 14. The V3 loop sequences consisted of a relatively conserved segment of seven amino acids and five adjacent residues that were allowed to vary in proportion to their seroprevalence among HIV-1 isolates of North America and Europe. A technique called random systematic mutagenesis was used to incorporate the composite V3 loop sequences flanked by zero to two randomized amino acids. This library could contain 2.7 x 10(8) members having diverse sequences and conformations. Immunoselection of a portion of this library by using two neutralizing V3 loop-directed monoclonal antibodies followed by selection for desirable growth and purification characteristics yielded a set of chimeric rhinoviruses, five of which are described. The inserted sequences in the five chimeras do not match those of any known isolate of HIV-1. Nonetheless, all five chimeras were neutralized by antibodies directed against different strains of HIV 1 and were able to elicit the production of antibodies that bind V3 loop peptides from diverse HIV-1 isolates. Moreover, antisera derived from four of the five chimeras were capable of neutralizing one or more strains of HIV-1 in cell culture. This study demonstrates that random systematic mutagenesis in conjunction with antibody screening is a powerful and efficient means to obtain antigenic chimeras with relevant immunogenic properties. PMID- 7884888 TI - Functional cDNA clones of the human respiratory syncytial (RS) virus N, P, and L proteins support replication of RS virus genomic RNA analogs and define minimal trans-acting requirements for RNA replication. AB - The RNA-dependent RNA polymerase of human respiratory syncytial (RS) virus was expressed in a functional form from a cDNA clone. Coexpression of the viral polymerase (L) protein, phosphoprotein (P), and nucleocapsid (N) protein allowed us to develop a system for expression and recovery of replicable RS virus RNA entirely from cDNA clones. cDNA clones of the N, P, and L genes were constructed in pGEM-based expression plasmids and shown to direct expression of the appropriate polypeptides. Two types of RS virus genomic RNA analogs were expressed from an intracellular transcription plasmid that directed the synthesis of RNAs with defined 5' and 3' ends. One analog included the authentic 5' and 3' termini of the genome, and the second contained the authentic 5' terminus and its complement at the 3' terminus as found in copyback defective interfering RNAs of other negative-strand RNA viruses. Both types of genomic analogs were encapsidated and replicated in cells expressing the RS virus N, P, and L proteins. Omission of any of the three viral proteins abrogated replication, thereby defining the N, P, and L proteins as the minimal trans-acting proteins required for RNA replication. This system has the advantages that expression occurs at a level sufficient to allow direct biochemical analysis of the products of RNA replication and that neither the use of reporter genes nor wild-type RS helper virus is required. These features allow analysis of both cis- and trans acting factors involved in the control of replication of RS virus RNA. PMID- 7884889 TI - Individual expression of influenza virus PA protein induces degradation of coexpressed proteins. AB - In the process of in vivo reconstitution of influenza virus transcriptase replicase complex, an inhibitory effect was observed when the level of PA protein expression was increased. This inhibition was paralleled by a decrease in the accumulation of the other influenza virus core proteins. The sole expression of PA protein was sufficient to reduce the accumulation level of the proteins encoded by the coexpressed genes. The PA effect was observed upon influenza virus and non-influenza virus proteins and independently of the expression system chosen and the origin of cell line used. The expression of PA protein did not induce variations in the translation of the target proteins but did induce variations on their half-lives, which were clearly reduced. A functional PA subunit seems to be necessary to induce this negative effect, because an inactive point mutant was unable to decrease the steady-state levels or the half-lives of the reporter proteins. The PA effect was observed as early as 5 h after its expression, and continuous synthesis of proteins was not required for performance of its biological activity. The results presented represent the first biological activity of individually expressed PA polymerase subunit. PMID- 7884890 TI - Influenza virus NS1 protein enhances the rate of translation initiation of viral mRNAs. AB - The effect of NS1 protein on the efficiency of influenza virus mRNA translation was evaluated by determining the accumulation of nucleoprotein (NP) or M1 mRNAs in the cytoplasm of cells expressing either of these genes alone or in combination with the NS1 gene, as well as the total cell accumulation of NP or M1 protein. Coexpression of NS1, but not of NS2 protein, led to increases in the translation of these mRNAs in the range of 5- to 100-fold. This translation enhancement was specific for viral mRNAs, since the translation of neither cat nor lacZ mRNAs was affected by the coexpression of NS1 protein. The use of chimeric cat genes containing the 5'-extracistronic sequences of the influenza virus mRNAs corresponding to segment 2, 7, or 8 indicated that these sequences can in part account for the observed effect. The enhancement of viral mRNA translation mediated by NS1 protein was due to an increase in the translation initiation rate, since the sizes of NP-specific polysomes, but not those of lacZ specific polysomes, was significantly higher in cells coexpressing NS1 protein than in those expressing only the NP gene. PMID- 7884891 TI - The JC virus minimal core promoter is glial cell specific in vivo. AB - The glial cell specificity of the human papovavirus JC (JCV), an etiologic agent for progressive multifocal leukoencephalopathy, is thought to be due to the presence of both positive and negative regulatory elements upstream of the TATA region within the JCV promoter. Here we report that the JCV minimal core promoter, containing only the TATA box and an 8-bp poly(T) region immediately upstream, is sufficient to initiate transcription of an attached gene in glial cells and functions as an autonomously active initiator. We further define the sequences required for this core promoter's glial cell specificity by appropriate substitution and point mutation analysis. Ectopic expression of Tst-1, a POU domain transcription factor that has been implicated in the regulation of oligodendrocyte development, leads to higher activation of the JCV minimal core promoter in Tst-1-deficient glial cells than in non-glial HeLa cells. These results suggest a requirement for a glial cell coactivator(s) for the optimum activation of the JCV minimal core promoter by Tst-1. A discrete affinity of Tst 1 for the JCV core promoter (Kd, 1.4 x 10(-8) M) is also shown to be optimal for its promoter strength. Mutations within the core promoter that maintain this affinity for Tst-1 show maintenance of promoter strength, whereas mutants carrying a change that results in an increased affinity for Tst-1 show reduced transcriptional activity. These results suggest that moderate affinity of Tst-1 for the JCV TATA region may allow the interaction of some glial cell-specific coactivator(s) along with the basal transcription machinery to direct glial cell specific transcription from the JCV core promoter. PMID- 7884892 TI - The majority of cells are superinfected in a cloned cell line that produces high levels of human immunodeficiency virus type 1 strain MN. AB - We have isolated seven single-cell clones from an H9 culture infected with human immunodeficiency virus type 1 strain MN so that a stable producer of virus could be obtained. DNAs from these clones were examined by Southern blot analysis and found to contain between one and four proviruses per clone. One of these cell lines, Clone 4, produced high levels of replication-competent virus and contained two proviruses. Southern blot analysis of DNAs from Clone 4 revealed that, after extended culture, some of the cells had acquired additional proviruses, presumably by superinfection. Analysis of Clone 4 single-cell subclones isolated from a late-passage culture found that 14 out of 20 (70%) subclones were reinfected and that 8 out of 20 (40%) were reinfected more than once. Fluorescence-activated cell sorter analysis showed that surface CD4 levels on Clone 4 cells were appropriately down-regulated. Our results indicate that while there is significant interference to superinfection in the Clone 4 culture, it is not absolute and that superinfected cells accumulate in the culture over time in the presence of high virus exposure and extensive cell-to-cell contact. Given our data, it seems likely that superinfection can occur in vivo within the lymphoid reservoirs that harbor human immunodeficiency virus type 1 during the clinically latent period and may contribute to disease progression. PMID- 7884893 TI - Mode of action of SDZ NIM 811, a nonimmunosuppressive cyclosporin A analog with activity against human immunodeficiency virus (HIV) type 1: interference with HIV protein-cyclophilin A interactions. AB - Cyclosporins, in particular the nonimmunosuppressive derivative SDZ NIM 811, exhibit potent anti-human immunodeficiency virus type 1 (HIV-1) activity in vitro. SDZ NIM 811 interferes at two stages of the viral replication cycle: (i) translocation of the preintegration complex to the nucleus and (ii) production of infectious virus particles. Immunosuppressive activity is not correlated with anti-HIV-1 activity of cyclosporins. However, binding to cyclophilin A, the major cellular receptor protein of cyclosporins, is a prerequisite for HIV inhibition: all structural changes of the cyclosporin A molecule leading to loss of affinity to cyclophilin abolished the antiviral effect. Cyclosporin derivatives did not interact directly with HIV-1 proteins; cyclophilin was the only detectable receptor protein for antivirally active cyclosporins. There is no evidence that inhibition of HIV occurs via a gain of function of cyclophilin in the presence of cyclosporins: the complex of cyclophilin A with SDZ NIM 811 does not bind to calcineurin or to any other viral or cellular proteins under conditions in which calcineurin binding to the cyclophilin A-cyclosporin A complex is easily detectable. Thus, the loss of function caused by binding of cyclosporins to cyclophilin seems to be sufficient for the anti-HIV effect. Cyclophilin A was demonstrated to bind to HIV-1 p24gag, and the formation of complexes was blocked by cyclosporins with 50% inhibitory concentrations of about 0.7 microM. HIV-2 and simian immunodeficiency virus are only weakly or not at all inhibited by cyclosporins. For gag-encoded proteins derived from HIV-1, HIV-2, or simian immunodeficiency virus particles, cyclophilin-binding capacity correlated with sensitivity of the viruses to inhibition by cyclosporins. Cyclophilin A also binds to HIV-1 proteins other than gag-encoded proteins, namely, p17gag, Nef, Vif, and gp120env; the biological significance of these interactions is questionable. We conclude that HIV-1 Gag-cyclophilin A interaction may be essential in HIV-1 replication, and interference with this interaction may be the molecular basis for the antiviral activity of cyclosporins. PMID- 7884894 TI - Patients with chronic hepatitis C have circulating cytotoxic T cells which recognize hepatitis C virus-encoded peptides binding to HLA-A2.1 molecules. AB - Antiviral cytotoxic T lymphocytes (CTL) may play a role in clearance of hepatitis C virus (HCV)-infected cells and thereby cause hepatocellular injury during acute and chronic HCV infection. The aim of this study was to identify HLA-A2.1 restricted HCV T-cell epitopes and to evaluate whether anti-HCV-specific CTL are present during chronic hepatitis C. Peripheral blood mononuclear cells from four HLA-A2-positive patients with chronic hepatitis C and from two individuals after recovery from HCV infection were tested against a panel of HCV-encoded peptides derived from different regions of the genome, including some peptides containing HLA-A2.1 binding motifs. HLA-A2-negative patients with chronic hepatitis C as well as healthy HLA-A2-positive (anti-HCV-negative) donors served as controls. Peripheral blood mononuclear cells stimulated repeatedly with several HCV-encoded peptides (three in core, one in NS4B, and one in NS5B) yielded cytolytic responses. All four HLA-A2-positive patients with active infection had CTL specific for at least one of the identified epitopes, whereas two patients who had recovered from HCV infection had almost no CTL responses. Monoclonal antibody blocking experiments performed for two epitopes demonstrated a class I- and HLA A2-restricted CTL response. CTL epitopes could partially be predicted by HLA-A2 binding motifs and more reliably by quantitative HLA-A2.1 molecule binding assays. Most of the identified epitopes could also be produced via the endogenous pathway. Specific CTL against multiple, mostly highly conserved epitopes of HCV were detected during chronic HCV infection. This finding may be important for further investigations of the immunopathogenesis of HCV, the development of potential therapies against HCV on the basis of induction or enhancement of cellular immunity, and the design of vaccines. PMID- 7884895 TI - Mutations in the putative fusion peptide of Semliki Forest virus affect spike protein oligomerization and virus assembly. AB - The two transmembrane spike protein subunits of Semliki Forest virus (SFV) form a heterodimeric complex in the rough endoplasmic reticulum. This complex is then transported to the plasma membrane, where spike-nucleocapsid binding and virus budding take place. By using an infectious SFV clone, we have characterized the effects of mutations within the putative fusion peptide of the E1 spike subunit on spike protein dimerization and virus assembly. These mutations were previously demonstrated to block spike protein membrane fusion activity (G91D) or cause an acid shift in the pH threshold of fusion (G91A). During infection of BHK cells at 37 degrees C, virus spike proteins containing either mutation were efficiently produced and transported to the plasma membrane, where they associated with the nucleocapsid. However, the assembly of mutant spike proteins into mature virions was severely impaired and a cleaved soluble fragment of E1 was released into the medium. In contrast, incubation of mutant-infected cells at reduced temperature (28 degrees C) dramatically decreased E1 cleavage and permitted assembly of morphologically normal virus particles. Pulse-labeling studies showed that the critical period for 28 degrees C incubation was during virus assembly, not spike protein synthesis. Thus, mutations in the putative fusion peptide of SFV confer a strong and thermoreversible budding defect. The dimerization of the E1 spike protein subunit with E2 was analyzed by using either cells infected with virus mutants or mutant virus particles assembled at 28 degrees C. The altered-assembly phenotype of the G91D and G91A mutants correlated with decreased stability of the E1-E2 dimer. PMID- 7884896 TI - Tyrosine phosphorylation of measles virus nucleocapsid protein in persistently infected neuroblastoma cells. AB - Subacute sclerosing panencephalitis is a slowly progressing fatal human disease of the central nervous system which is a delayed sequel of measles virus (MV) infection. A typical pathological feature of this disease is the presence of viral ribonucleocapsid structures in the form of inclusion bodies and the absence of infectious virus or budding viral particles. The mechanisms governing the establishment and maintenance of a persistent MV infection in brain cells are still largely unknown. To understand the mechanisms underlying MV persistence in neuronal cells, a tissue culture model was studied. Clone NS20Y/MS of the murine neuroblastoma C1300 persistently infected with the wild-type Edmonston strain of MV secretes relatively high levels of alpha/beta interferon (IFN). As shown previously, treatment of the persistently infected cultures with anti-IFN serum converted the persistent state into a productive infection indicated by the appearance of multinucleated giant cells. In this study, we have investigated whether alpha/beta IFN produced by NS20Y/MS cells activates cellular protein tyrosine kinases which will induce tyrosine phosphorylating activity specific to virus-infected cells. We present data to show augmented protein tyrosine kinase activity in the persistently infected cells. We demonstrate that the MV N protein is phosphorylated on tyrosine in addition to serine and threonine in the persistent state but not in NS20Y cells acutely infected with MV. PMID- 7884897 TI - Multiple regions of Harvey sarcoma virus RNA can dimerize in vitro. AB - Retroviruses contain a dimeric RNA consisting of two identical molecules of plus strand genomic RNA. The structure of the linkage between the two monomers is not known, but they are believed to be joined near their 5' ends. Darlix and coworkers have reported that transcripts of retroviral RNA sequences can dimerize spontaneously in vitro (see, for example, E. Bieth, C. Gabus, and J. L. Darlix, Nucleic Acids Res. 18:119-127, 1990). As one approach to identification of sequences which might participate in the linkage, we have mapped sequences derived from the 5' 378 bases of Harvey sarcoma virus (HaSV) RNA which can dimerize in vitro. We found that at least three distinct regions, consisting of nucleotides 37 to 229, 205 to 272, and 271 to 378, can form these dimers. Two of these regions contain nucleotides 205 to 226; computer analysis suggests that this region can form a stem-loop with an inverted repeat in the loop. We propose that this hypothetical structure is involved in dimer formation by these two transcripts. We also compared the thermal stabilities of each of these dimers with that of HaSV viral RNA. Dimers of nucleotides 37 to 229 and 205 to 272 both exhibited melting temperatures near that of viral RNA, while dimers of nucleotides 271 to 378 are quite unstable. We also found that dimers of nucleotides 37 to 378 formed at 37 degrees C are less thermostable than dimers of the same RNA formed at 55 degrees C. It seems possible that bases from all of these regions participate in the dimer linkage present in viral RNA. PMID- 7884898 TI - E2F1 overexpression in quiescent fibroblasts leads to induction of cellular DNA synthesis and apoptosis. AB - Various experiments have demonstrated a role for the E2F transcription factor in the regulation of cell growth during the G0/G1/S phase transition. Indeed, overexpression of the E2F1 product, a component of the cellular E2F activity, induces DNA synthesis in quiescent fibroblasts. To provide an approach to a more detailed biochemical analysis of these events, we have made use of a recombinant adenovirus containing the E2F1 cDNA in order to efficiently express the E2F1 product in an entire population of cells. We demonstrate an induction of DNA synthesis when quiescent cells are infected with the E2F1 recombinant virus. However, we also find that the induction does not lead to a complete replication of the cellular genome, as revealed by flow cytometry. The incomplete nature of cellular DNA replication is due, at least in part, to the fact that E2F1 overexpression leads to massive cell death that is characteristic of apoptosis. This E2F1-mediated induction of apoptosis is largely dependent on endogenous wild type p53 activity and can be subverted by introducing mutant forms of p53 into these cells or by overexpressing E2F1 in fibroblasts derived from p53-null mouse embryos. We conclude that E2F1 can induce events leading to S phase but that the process is not normal and appears to result from the activation of a cell death pathway. PMID- 7884899 TI - Fgf-8, activated by proviral insertion, cooperates with the Wnt-1 transgene in murine mammary tumorigenesis. AB - We have used mouse mammary tumor virus (MMTV) infection of Wnt-1 transgenic mice to accelerate mammary tumorigenesis and to molecularly tag insertionally activated proto-oncogenes that cooperate oncogenically with Wnt-1 (G. M. Shackleford, C. A. MacArthur, H. C. Kwan, and H. E. Varmus, Proc. Natl. Acad. Sci. USA 90:740-744, 1993). Here we report the identification and characterization of a 31-kb genomic locus that contains clonal MMTV integrations in 8 of 80 mammary tumors from MMTV-infected Wnt-1 transgenic mice. Two genes were identified within this locus, one of which was transcriptionally activated by MMTV insertions. This activated gene is identical to androgen-induced growth factor (AIGF/Fgf-8) (A. Tanaka, K. Miyamoto, N. Minamino, M. Takeda, B. Sato, H. Matsuo, and K. Matsumoto, Proc. Natl. Acad. Sci. USA 89:8928-8932, 1992), the eighth member of the fibroblast growth factor (FGF) family. Transcriptional activation of Fgf-8 was found in all tumors with MMTV insertions in this locus. Fgf-8 mRNA was absent in normal mammary glands and was detected only in adult testis and ovary and in midgestational embryos. The sequences of Fgf-8 genomic and cDNA clones revealed five coding exons, in contrast to the three coding exons found in other FGF genes. cDNAs encoding three isoforms of the FGF-8 protein were isolated. The three corresponding mRNAs resulted from the alternative use of two 5' splice sites and two 3' splice sites for the second and third exons, respectively. These results implicate Fgf-8 as the third FGF gene found to cooperate with Wnt-1 in MMTV-induced murine mammary tumorigenesis, suggesting that FGFs and Wnts are strong collaborators in this process. PMID- 7884900 TI - Functional domains of delta antigens and viral RNA required for RNA packaging of hepatitis delta virus. AB - The functions of delta antigens (HDAgs) in the morphogenesis of hepatitis delta virus (HDV) have been studied previously. The C terminus of large HDAg has been shown to complex with the small surface antigen (HBsAg) of helper hepatitis B virus, whereas the assembly of small HDAg requires interaction with the N terminus of large HDAg (M.-F. Chang, C.-J. Chen, and S. C. Chang, J. Virol. 68:646-653, 1994). To further examine the molecular mechanisms by which HDAgs are involved in the assembly of HDV RNA, we have cotransfected Huh-7 cells with plasmids representing a longer than unit-length HDV and the small HBsAg cDNAs. We found that HDAg mRNA could be generated from an endogenous promoter within the HDV cDNA that was translated into large HDAg. Large HDAg is capable of complexing with monomeric HDV genomic RNA to form ribonucleoprotein particles (RNPs) and is capable of forming enveloped HDV-like particles in the presence of small HBsAg without undergoing HDV replication. In addition, the middle region from amino acid residues 89 to 145 of large HDAg is required for assembly of the RNPs but is dispensable for assembly of the enveloped particles. RNA assembly is also demonstrated with small HDAg when it is cotransfected with a packaging-defective large HDAg mutant and small HBsAg. Leu-115 within the putative helix-loop-helix structure of the small HDAg is important for the replication of HDV but is not essential for RNA assembly, suggesting that conformational requirements of small HDAg for replication and assembly of viral RNA may be different. Further studies indicate that a 312-nucleotide linear HDV RNA from one end of the HDV and structure is sufficient to form RNP complexes competent for assembly of virus like particles with large HDAg and small HBsAg. PMID- 7884901 TI - Mutations in the DNA-binding and transcriptional activation domains of v-Myb cooperate in transformation. AB - The v-Myb protein encoded by avian myeloblastosis virus causes oncogenic transformation of monoblastic cells committed to the monocyte/macrophage lineage. v-Myb is a doubly truncated form of its normal cellular counterpart, c-Myb. In addition to its N- and C-terminal deletions, v-Myb contains a number of amino acid substitutions relative to c-Myb. We have previously shown that neither overexpression of c-Myb nor introduction of these amino acid substitutions into c Myb is sufficient for transformation of myelomonocytic cells. However, a doubly truncated form of c-Myb which lacked these substitutions transformed myeloblastic cells that appeared to be committed to the granulocytic pathway. We demonstrate here that mutations in both the DNA-binding and transcriptional activation domains of v-Myb are required for transformation of rapidly growing monoblasts rather than more slowly growing myeloblasts. These rapidly growing monoblasts do not express mim-1, a target gene for the Gag-Myb-Ets protein of E26 leukemia virus, or C/EBP proteins which cooperate with Myb to activate mim-1 expression. Furthermore, v-Myb proteins which contain both sets of these mutations are weaker transcriptional activators relative to proteins which lack these mutations. These results support a model in which amino acid substitutions in v-Myb have been selected for their ability to activate only a subset of those genes which can be activated by a doubly truncated form of c-Myb. In particular, mim-1 appears to represent a class of genes whose expression was selected against during the development of an increasingly virulent strain of avian myeloblastosis virus by passage in animals. PMID- 7884902 TI - The predominant virus antigen burden is present in macrophages in Theiler's murine encephalomyelitis virus-induced demyelinating disease. AB - Theiler's murine encephalomyelitis virus (TMEV) produces a persistent central nervous system infection and chronic, inflammatory demyelinating disease in susceptible mice. TMEV antigen(s) and RNA genome have been detected in astrocytes, oligodendrocytes, and macrophages during persistence. Whether there is a predominant cell type in which TMEV persists has not been resolved. Since TMEV-induced demyelinating lesions are infiltrated with macrophages and a number of other persistent viruses show near-exclusive tropism for these phagocytic cells, we used two-color immunofluorescent staining with conventional and confocal microscopy to colocalize TMEV to cells that stain with monoclonal antibodies (MOMA-2) [unknown antigen], Mac-1 [CD11b], FA-11 [CD66], and 2F8 [scavenger receptor]) to macrophages in BeAn-infected SJL mice. A predominant virus antigen burden within macrophages infiltrating demyelinating lesions was seen. A dichotomy of cells staining for virus antigen(s) was found with infected cells containing either a large or small virus antigen load. Ninety percent of cells with a large virus antigen load were large phagocytes (20 to 50 microns) that were readily detected at low power (5x objective). Cells with smaller amounts of virus antigen(s) turned out to be either these same large phagocytic cells or much smaller cells, approximately equal to 10 microns in diameter. Forty percent of cells with a small virus antigen load were macrophages. The unidentified approximately equal to 10-microns cells that are virus antigen positive and macrophage negative in this study could still be macrophages, or they may be oligodendrocytes. The fact that virus was detected in the cytoplasm and not phagolysosomes of macrophages and the sheer mass of fluorescently stained virus proteins in some macrophages suggest that TMEV persists in these phagocytic cells by active virus replication. PMID- 7884903 TI - NS3-4A of hepatitis C virus is a chymotrypsin-like protease. AB - The polyprotein encoded by a single open reading frame of hepatitis C virus (HCV) is processed by host- and virus-encoded proteases. The viral protease NS3 is responsible for the cleavage of at least four sites (NS3/4A, NS4A/4B, NS4B/5A, and NS5A/5B junctions) in the nonstructural protein region. To characterize the protease function of NS3 and NS4 on various target sites, efficient cis- and trans-cleavage assay systems were developed by using in vitro transcription and translation. Deletion of the C-terminal two-thirds from NS3 in an NS3-NS4A-4B polypeptide (NS3 delta C-4A-4B) hampered cleavage of the NS3/4A junction but not that of the NS4A/4B junction. As a consequence, expression of NS3 delta C-4A-4B containing an internal deletion of NS3 results in an NS3 delta C-4A fusion protein. NS3 delta C-4A shows very efficient and specific trans-cleavage activity at NS4A/4B, NS4B/5A, and NS5A/5B junctions. In addition, the biochemical properties of HCV NS3 delta C-4A were further elucidated by adding known protease inhibitors in trans-cleavage reactions. The HCV protease NS3-4A is inhibited by chymotrypsin-specific inhibitors N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), chymostatin, and Pefabloc SC but not by trypsin-like protease inhibitors antipain, leupeptin, and N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) or by the protease inhibitors E-64, bestatin, pepstatin, and phosphoramidon. This finding strongly suggests that HCV protease NS3-4A is a chymotrypsin-like serine protease. PMID- 7884904 TI - Effect of cellular differentiation on cytokine-induced expression of human immunodeficiency virus in chronically infected promonocytic cells: dissociation of cellular differentiation and viral expression. AB - Cellular differentiation is thought to play an important role in the susceptibility of monocytic lineage cells to human immunodeficiency virus (HIV) infection as well as in their ability to support virus replication. In addition, virus replication in monocytes/macrophages has been demonstrated in vitro to be strongly modulated by several cytokines such as tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor. The purpose of the present study was to investigate the interaction between cellular differentiation and cytokines in the regulation of HIV expression from chronically infected monocytic lineage cells. U1, a persistently HIV-infected promonocytic cell line, is characterized by low levels of virus expression which can be modulated by several cytokines. 1 alpha,-25-Dihydroxyvitamin D3 (Vit.D3), a well-known differentiating agent for myelomonocytic cells which has been previously reported to modulate HIV replication in other in vitro systems, induced maturation of U1 cells toward a macrophage-like phenotype, as demonstrated by the induction of the differentiation-associated cell surface markers CD14 and CD11b. Vit.D3-induced differentiation did not result in induction of HIV expression; however, when U1 cells were stimulated with tumor necrosis factor alpha in the presence of Vit.D3, a synergistic induction of cell differentiation and viral expression was demonstrated. In contrast, Vit.D3 suppressed the induction of HIV expression in U1 cells stimulated with gamma interferon, interleukin-6, and granulocyte macrophage colony-stimulating factor, although synergy between Vit.D3 and these cytokines was observed in terms of cellular differentiation. These data suggest that differentiation of monocytic cells does not necessarily correlate with increased HIV expression. PMID- 7884905 TI - Mutations in the helicase-like domain of protein 1a alter the sites of RNA-RNA recombination in brome mosaic virus. AB - A system that uses engineered heteroduplexes to efficiently direct in vivo crossovers between brome mosaic virus (BMV) RNA1 and RNA3 (P. Nagy and J. Bujarski, Proc. Natl. Acad. Sci. USA 90:6390-6394, 1993) has been used to explore the possible involvement of BMV 1a protein, an essential RNA replication factor, in RNA recombination. Relative to wild-type 1a, several viable amino acid insertion mutations in the helicase-like domain of BMV 1a protein affected the nature and distribution of crossover sites in RNA3-RNA1 recombinants. At 24 degrees C, mutants PK19 and PK21 each increased the percentage of asymmetric crossovers, in which the RNA1 and RNA3 sites joined by recombination were not directly opposite each other on the engineered RNA3-RNA1 heteroduplex used to target recombination but rather were separated by 4 to 85 nucleotides. PK21 and another 1a mutant, PK14, also showed increases in the fraction of recombinants containing nontemplated U residues at the recombination junction. At 33 degrees C, the highest temperature that permitted infections with PK19, which is temperature sensitive for RNA replication, the mean location of RNA1-RNA3 crossovers in recombinants recovered from PK19 infections was shifted by nearly 25 bp into the energetically less stable side of the RNA1-RNA3 heteroduplex. Thus, mutations in the putative helicase domain of the 1a protein can influence BMV RNA recombination. The results are discussed in relation to models for recombination by template switching during pausing of RNA replication at a heteroduplexed region in the template. PMID- 7884906 TI - Conservation of an intact human immunodeficiency virus type 1 vif gene in vitro and in vivo. AB - Replication of vif-negative human immunodeficiency virus type 1 (HIV-1) is attenuated in certain cell lines and highly impaired in peripheral blood lymphocytes in vitro. To determine whether intact vif is positively selected during natural HIV-1 infection and to determine vif sequence variability, we employed PCR amplification, cloning, and sequencing to investigate the vif region of replicating virus in short-term-passage HIV-1 primary isolates from five asymptomatic individuals and from five persons with AIDS. A total of 46 vif clones were obtained and analyzed. Recombinant proviruses were constructed from selected vif clones from one patient and found to be fully infectious. We found that 38 of the 46 clones sequenced carried open vif reading frames and that there was a low degree of heterogeneity of vif genes within isolates from the same individual and among isolates from different donors. The cysteines previously found to be essential for vif protein function were conserved in all clones. A phylogenetic tree constructed from all available vif nucleotide sequences resulted in a virus grouping similar to those of gag and env. Direct sequencing of vif amplified by PCR from uncultured lymphocytes of 15 individuals at various stages of progression toward AIDS demonstrated vif open reading frames in 13 of 15 samples tested. There was no obvious correlation between disease status and the presence of an intact vif within this sample group at the time of sample procurement. The conservation of the vif open reading frame in vitro and in vivo and its limited variability following virus transmission in vitro are consistent with a role for vif in natural HIV-1 infection. PMID- 7884907 TI - Tetracycline repressor-regulated gene repression in recombinant human cytomegalovirus. AB - The tetracycline repressor (TetR)-regulated gene expression system from Escherichia coli was used to control gene expression in recombinant human cytomegalovirus (HCMV). To adapt the TetR system in HCMV, derivatives of the viral US11 (early) gene promoter, which controls the beta-glucuronidase reporter gene, were constructed by systematic insertion of the tetracycline operator (tetO) sequences. Gene expression from constructs containing two or three appropriately placed tetO sequences adjacent to the TATA box were efficiently repressed by a TetR-VP16 fusion protein (tTA) in a transient expression system. Efficient repression (50- to 120-fold) also occurred in tTA-expressing stably transfected human cells which were infected with recombinant HCMV containing a US11 promoter surrounded by three tetO sequences. The tTA-mediated gene repression was relieved in the presence of 1 microgram of tetracycline per ml. The results of this study are significant in three respects. (i) This is the first demonstration that a TetR-derived protein can be used to efficiently repress gene expression in a mammalian system. (ii) Efficient repression was dependent on the presence of the transcriptional activation domain from the herpes simplex virus type 1 VP16 protein. (iii) The ability to regulate gene expression in a controlled fashion in order to elucidate viral gene function is an important development in the HCMV field. The tTA-mediated gene repression system may be extremely useful for creating host-range mutants in essential genes in order to study their role in the HCMV replicative cycle, a system that is otherwise exceedingly difficult to genetically dissect. PMID- 7884908 TI - DNA vaccination against persistent viral infection. AB - This study shows that DNA vaccination can confer protection against a persistent viral infection by priming CD8+ cytotoxic T lymphocytes (CTL). Adult BALB/c (H 2d) mice were injected intramuscularly with a plasmid expressing the nucleoprotein (NP) gene of lymphocytic choriomeningitis virus (LCMV) under the control of the cytomegalovirus promoter. The LCMV NP contains the immunodominant CTL epitope (amino acids 118 to 126) recognized by mice of the H-2d haplotype. After three injections with 200 micrograms of NP DNA, the vaccinated mice were challenged with LCMV variants (clones 13 and 28b) that establish persistent infection in naive adult mice. Fifty percent of the DNA-vaccinated mice were protected, as evidenced by decreased levels of infectious virus in the blood and tissues, eventual clearance of viral antigen from all organs tested, the presence of an enhanced LCMV-specific CD8+ CTL response, and maintenance of memory CTL after clearance of virus infection. However, it should be noted that protection was seen in only half of the vaccinated mice, and we were unable to directly measure virus-specific immune responses in any of the DNA-vaccinated mice prior to LCMV challenge. Thus, at least in the system that we have used, gene immunization was a suboptimal method of inducing protective immunity and was several orders of magnitude less efficient than vaccination with live virus. In conclusion, our results show that DNA immunization works against a persistent viral infection but that efforts should be directed towards improving this novel method of vaccination. PMID- 7884909 TI - Tick-borne thogoto virus infection in mice is inhibited by the orthomyxovirus resistance gene product Mx1. AB - We show that tick-transmitted Thogoto virus is sensitive to interferon-induced nuclear Mx1 protein, which is known for its specific antiviral action against orthomyxoviruses. Influenza virus-susceptible BALB/c mice (lacking a functional Mx1 gene) developed severe disease symptoms and died within days after intracerebral or intraperitoneal infection with a lethal challenge dose of Thogoto virus. In contrast, Mx1-positive congenic, influenza virus-resistant BALB.A2G-Mx1 mice remained healthy and survived. Likewise, A2G, congenic B6.A2G Mx1 and CBA.T9-Mx1 mice (derived from influenza virus-resistant wild mice) as well as Mx1-transgenic 979 mice proved to be resistant. Peritoneal macrophages and interferon-treated embryo cells from resistant mice exhibited the same resistance phenotype in vitro. Moreover, stable lines of transfected mouse 3T3 cells that constitutively express Mx1 protein showed increased resistance to Thogoto virus infection. We conclude that an Mx1-sensitive step has been conserved during evolution of orthomyxoviruses and suggest that the Mx1 gene in rodents may serve to combat infections by influenza virus-like arboviruses. PMID- 7884910 TI - The H4 subunit of vaccinia virus RNA polymerase is not required for transcription initiation at a viral late promoter. AB - Chromatography of RNA polymerase purified from vaccinia virions and from vaccinia virus-infected HeLa cells resulted in the separation of populations active for early and late transcription. An RNA polymerase population immunodepleted for the vaccinia virus H4 gene peptide could support late transcription. PMID- 7884911 TI - Delineating minimal protein domains and promoter elements for transcriptional activation by lentivirus Tat proteins. AB - Lentivirus Tat proteins comprise a novel class of RNA-binding transcriptional activators that are essential for viral replication. In this study, we performed a series of protein fusion experiments to delineate the minimal protein domains and promoter elements required for Tat action. We show that a 15-amino-acid region of equine infectious anemia virus (EIAV) Tat protein, when fused to the GAL4 or LexA DNA binding domain, can activate transcription in appropriate promoter contexts. In the natural human immunodeficiency virus type 1 long terminal repeat, activation by Tat is dependent on multiple binding sites for the cellular transcription factor SP1. We delineate a 114-amino-acid region of the SP1 glutamine-rich activation domain that when fused to the GAL4 DNA binding domain can support transcription activation by Tat. Using these Tat and SP1 derivatives, we show that Tat activation can be reconstructed on a completely synthetic promoter lacking all cis-acting elements unique to the human immunodeficiency virus long terminal repeat. Our results indicate that lentivirus Tat proteins have essential properties of typical cellular transcriptional activators and define useful reagents for studying the detailed mechanism of Tat action. PMID- 7884912 TI - Tax mutation associated with tropical spastic paraparesis/human T-cell leukemia virus type I-associated myelopathy. AB - Tumaco, Colombia, is an area with elevated rates of tropical spastic paraparesis/human T-cell leukemia virus type I (HTLV-I)-associated myelopathy (TSP/HAM). We have identified a mutation in nucleotide 7959 of the tax gene of 14 Tumaco HTLV-I isolates (14 positive of 14 tested) that was present in 5 of 14 (35%) TSP/HAM patients from Japan and in 8 of 11 (72%) TSP/HAM patients from other geographic locations. In contrast, this mutation was found in only 2 of 21 (9.5%) HTLV-I-infected subjects outside of Tumaco who did not have TSP/HAM. tax clones with nucleotide mutations including one at nucleotide 7959 showed a greater ability to transactivate the HTLV-I U3 promoter. However, this effect was not observed when two clones that differed only in nucleotide 7959 were compared. These results suggest that HTLV-I-infected individuals carrying isolates with this tax mutation are at higher risk for developing TSP/HAM. PMID- 7884913 TI - Chromosome mapping of Rfv3, a host resistance gene to Friend murine retrovirus. AB - Inoculation of adult mice with Friend virus complex usually induces rapid viremia and erythroleukemia, resulting in death in 1 to 3 months. In certain mouse strains, a single host gene, Rfv3, controls the ability to mount a virus-specific neutralizing antibody response which results in elimination of viremia. In this study, microsatellite markers were used to localize the Rfv3 gene to a 20 centimorgan region of mouse chromosome 15 unlinked to immunoglobulin loci, T-cell receptor loci, or the major histocompatibility complex. Potential candidate genes for Rfv3 are several genes expressed in cells of the immune system and previously mapped to the same region, including a T-cell antigen gene, Ly6, and three cytokine receptor genes, IL2rb, IL3rb1, and IL3rb2. PMID- 7884914 TI - Simian AIDS type D serogroup 2 retrovirus: isolation of an infectious molecular clone and sequence analyses of its envelope glycoprotein gene and 3' long terminal repeat. AB - We describe the molecular cloning of a serogroup 2 simian retrovirus (SRV; D2/RHE/OR) and present the sequence of its envelope (env) glycoprotein gene and 3' long terminal repeat region. This report documents the first infectious molecular clone of a serogroup 2 SRV and provides env sequence verification of genetic diversity among serogroup 2 SRV isolates. PMID- 7884915 TI - Mapping the hemagglutination domain of rotaviruses. AB - Most strains of animal rotaviruses are able to agglutinate erythrocytes, and the surface protein VP4 is the virus hemagglutinin. To map the hemagglutination domain on VP4 while preserving the conformation of the protein, we constructed full-length chimeras between the VP4 genes of hemagglutinating (YM) and nonhemagglutinating (KU) rotavirus strains. The parental and chimeric genes were expressed in insect cells, and the recombinant VP4 proteins were evaluated for their capacity to agglutinate human type O erythrocytes. Three chimeric genes, encoding amino acids 1 to 208 (QKU), 93 to 208 (QC), and 93 to 776 (QYM) of the YM VP4 protein in a KU VP4 background, were constructed. YM VP4 and chimeras QKU and QC were shown to specifically hemagglutinate, indicating that the region between amino acids 93 and 208 of YM VP4 is sufficient to determine the hemagglutination activity of the protein. PMID- 7884916 TI - An EBNA-1-dependent enhancer acts from a distance of 10 kilobase pairs to increase expression of the Epstein-Barr virus LMP gene. AB - Upon infection of human B lymphocytes, the 172-kbp Epstein-Barr virus genome forms a covalently closed circle via its terminal repeats. This event brings all of the promoters that control expression of the latent gene products, and the viral origin of plasmid replication, oriP, within a 20-kbp stretch of contiguous DNA. We have found that the EBNA-1-dependent transcriptional enhancer FR, located in oriP, increased the expression of a tagged viral oncogene encoding the latent membrane protein (LMP) up to 200-fold in normal Epstein-Barr virus-positive cells. The effect of FR was exerted across 10 kbp of viral DNA that spans the circularized ends of the viral genome. Enhancement of the tagged LMP gene by FR/EBNA-1 did not require the EBNA-2-responsive element. PMID- 7884917 TI - The human immunodeficiency virus type 1 Tat antagonist, Ro 5-3335, predominantly inhibits transcription initiation from the viral promoter. AB - Tat, the transcriptional transactivator protein of the human immunodeficiency virus type 1 (HIV-1), is required for viral replication in vitro. The Tat antagonist, Ro 5-3335, and its analog, Ro 24-7429, have been shown to inhibit replication of HIV-1 and to reduce steady-state viral RNA in infected cells (M. C. Hsu et al., Science 254:1799-1802, 1991, and M.-C. Hsu et al., Proc. Natl. Acad. Sci. USA 90:6395-6399, 1993). Analysis of HIV-1 long terminal repeat-driven reporter gene transcription in a recombinant adenovirus by nuclear run-on assay indicated that the drug predominantly inhibits Tat-dependent initiation and also exerts a measurable effect on elongation. This result may imply a common mechanism for Tat-mediated transcription initiation and elongation. PMID- 7884918 TI - Epstein-Barr virus lytic replication is controlled by posttranscriptional negative regulation of BZLF1. AB - Regulation of the immediate-early gene BZLF1 is assumed to play a key role in triggering the lytic replication of Epstein-Barr virus (EBV). The expression of BZLF1 is regulated on multiple levels, including control of transcription by several positive and negative cis-acting elements as well as posttranslational modifications and protein-protein interactions. Localization of BZLF1 on one strand of the genome and the latent EBNA1 transcription unit on the complementary strand suggests a regulatory mechanism via hybridization of antisense RNA. With a plasmid encoding a defective BZLF1 RNA, which could not be translated, we were able to induce expression of endogenous BZLF1 gene product Zta and other proteins of the lytic cycle. Our data show for the first time that latent replication is stabilized by negative regulation of an immediate-early gene of the lytic cycle by a posttranscriptional mechanism. This might be a common theme of herpes simplex virus and EBV latency. PMID- 7884919 TI - Retroviral vector particles displaying the antigen-binding site of an antibody enable cell-type-specific gene transfer. AB - Retroviral vectors are the most efficient tool for stably introducing genes into vertebrate cells. However, their use is limited by the host range of the retrovirus from which they are derived. To alter the host range, we recently constructed retrovirus vector particles, derived from spleen necrosis virus, that display a single-chain antigen-binding site of an antibody (scA) on the viral surface (T.-H. T. Chu, I. Martinez, W. Sheay, and R. Dornburg, Gene Ther. 1:292 299, 1994). Using a hapten (2,4-dinitrophenol) model system, we showed that such particles are competent for infection. In this study, we repeated our experiments using an scA directed against a cell surface protein expressed on various human carcinoma cell lines. We found that such scA-displaying particles can efficiently infect human cells that express the corresponding antigen. Particles with wild type spleen necrosis virus envelope are minimally infectious on such cells. The addition of the original monoclonal antibody to the viral vector particle solution prior to infection inhibited infection. This competition assay showed that the infection is mediated by the antibody moiety and, therefore, is antibody specific. These data indicate that retroviral vectors with antibody-envelope fusion proteins may be a valuable tool for selectively introducing genes into any target cell. PMID- 7884920 TI - Respiratory syncytial virus matures at the apical surfaces of polarized epithelial cells. AB - Respiratory syncytial (RS) virus infects the epithelium of the respiratory tract. We examined the replication and maturation of RS virus in two polarized epithelial cell lines, Vero C1008 and MDCK. Electron microscopy of RS virus infected Vero C1008 cells revealed the presence of pleomorphic viral particles budding exclusively from the apical surface, often in clusters. The predominant type of particle was filamentous, 80 to 100 nm in diameter, and 4 to 8 microns in length, and evidence from filtration studies indicated that the filamentous particles were infectious. Cytopathology produced by RS virus infection of polarized Vero C1008 cells was minimal, and syncytia were not observed, consistent with the maintenance of tight junctions and the exclusively apical maturation of the virus. Infectivity assays with MDCK cells confirmed that in this cell line, RS virus was released into the apical medium but not into the basolateral medium. In addition, the majority of the RS virus transmembrane fusion glycoprotein on the cell surface was localized to the apical surface of the Vero C1008 cells. Taken together, these results demonstrate that RS virus matures at the apical surface of polarized epithelial cell lines. PMID- 7884921 TI - Varicella-zoster virus (VZV) transcription during latency in human ganglia: prevalence of VZV gene 21 transcripts in latently infected human ganglia. AB - Reverse transcriptase-linked PCR was used to determine the prevalence of varicella-zoster virus (VZV) gene 21 transcription in latently infected human ganglia. Under conditions wherein reverse transcriptase-linked PCR detected > or = 1,000 transcripts, VZV gene 21 RNA, but not VZV gene 40 RNA, was found in ganglia but not other tissues from five of seven humans. PMID- 7884922 TI - Molecular characterization of the 3' terminus of the simian hemorrhagic fever virus genome. AB - The 3' end of the simian hemorrhagic fever virus (SHFV) single-stranded RNA genome was cloned and sequenced. Adjacent to the 3' poly(A) tract, we identified a 76-nucleotide noncoding region preceded by two overlapping reading frames (ORFs). The ultimate 3' ORF of the viral genome encodes the capsid protein, and the penultimate ORF encodes the smallest SHFV envelope protein. These two ORFs overlap each other by 26 nucleotides. Northern (RNA) blot hybridization analyses of cytoplasmic RNA extracts from SHFV-infected MA-104 cells with gene-specific probes revealed the presence of full-length genomic RNA as well as six subgenomic SHFV-specific mRNA species. The subgenomic mRNAs are 3' coterminal. In its virion morphology and size, genome structure and length, and replication strategy, SHFV is most similar to lactate dehydrogenase-elevating virus, equine arteritis virus, and porcine reproductive and respiratory syndrome virus. PMID- 7884923 TI - DNA immunization confers protection against lethal lymphocytic choriomeningitis virus infection. AB - DNA vaccination has been evaluated with the lymphocytic choriomeningitis virus (LCMV) model system. Plasmid DNA encoding the LCMV nucleoprotein, when injected intramuscularly, induces both antiviral antibodies and cytotoxic T lymphocytes. Injection of DNA encoding the nucleoprotein or the viral glycoprotein confers protection against normally lethal LCMV challenge in a major histocompatibility complex-dependent manner. The protection conferred is incomplete, but it is most probably mediated by the induced cytotoxic T lymphocytes. PMID- 7884924 TI - A spontaneous mutation in the movement protein gene of brome mosaic virus modulates symptom phenotype in Nicotiana benthamiana. AB - Brome mosaic virus (BMV) is a positive-strand RNA virus with a multipartite genome that causes symptomless infection in Nicotiana benthamiana. We have isolated and characterized a strain of BMV that produced uniform vein chlorosis in systemically infected N. benthamiana. Analysis of pseudorecombinants constructed by exchanging RNA 1 and 2 and RNA 3 components between wild-type (non symptom-inducing) and vein chlorosis-inducing strains of BMV indicated that the genetic determinant for the induction of the chlorotic phenotype is located on RNA 3. Sequence analysis of progeny RNA 3 recovered from symptomatic N. benthamiana plants revealed that vein chlorosis is due to the single nucleotide transition 887G-->887A, which changes the codon for Val-266 to Ile-266 in the movement protein gene. The mutation had no detectable effect on the accumulation of virus in either inoculated or systematically infected leaves of N. benthamiana. The vein chlorosis phenotype is the manifestation of the substitution of Ile-266 for Val-266 in the movement protein gene, since additional alterations in this region (a silent mutation, i.e., 887GUU889-->GUC, and an alteration of valine to phenylalanine, i.e., 887GUU889-->887UUU889) resulted in symptomless infections on N. benthamiana. The modulation of the symptom phenotype by the substitution of Ile-266 for Val-266 is specific for N. benthamiana, since neither movement nor the symptom phenotype in barley plants was affected. PMID- 7884925 TI - Symmetric-strand packaging of recombinant parvovirus LuIII genomes that retain only the terminal regions. AB - LuIII is an autonomous parvovirus which encapsidates either strand of its genome with similar efficiency in NB324K cells. Two parvoviruses closely related to LuIII, minute virus of mice (MVM) and H-1 virus, encapsidate primarily the minus strand of their genome when grown in the same cell type. It has been postulated that an AT-rich region unique to LuIII is responsible for symmetric encapsidation of plus- and minus-strand genomes by LuIII. To address this hypothesis, recombinant LuIII-luciferase genomes containing or lacking the AT-rich sequence (AT) were packaged into LuIII virions. Hybridization of strand-specific probes to DNA from these virions revealed that either strand of the genome was packaged regardless of the presence of AT. In addition, encapsidation of both strands of the AT+ LuIII-luciferase genome into MVM and H-1 virions was observed, suggesting that MVM and H-1 viral proteins are not responsible for the minus-strand packaging bias of these two viruses. Alignment of the published LuIII and MVMp sequences shows that AT exists as an insertion into an element that, in MVM, binds cellular proteins. We suggest that in LuIII, AT disrupts binding of these cellular proteins, allowing encapsidation of either strand. PMID- 7884926 TI - Encephalomyocarditis viruses with short poly(C) tracts are more virulent than their mengovirus counterparts. AB - We have constructed three cDNA clones of encephalomyocarditis virus strain R (EMCV-R) with poly(C) tracts of C4, C9, and C20. RNA transcribed from these cDNAs was infectious to HeLa cells, and the resultant viruses grew well in this system, albeit with plaque sizes that were proportional to the poly(C) length. When injected into mice, the progeny viruses were only slightly less pathogenic than EMCV-R, and the observed degree of attenuation was not nearly as dramatic as for equivalent mengoviruses with similar short poly(C)s. Short-tract poly(C)-mediated attenuation is therefore highly dependent on viral genomic context. PMID- 7884927 TI - Impairment of multicycle influenza virus growth in Vero (WHO) cells by loss of trypsin activity. AB - We demonstrated that influenza virus replication in Vero (WHO) cells, a subline of African green monkey kidney cells, is impaired by rapid inactivation of trypsin in the culture fluids. Trypsin inactivation was caused by a factor secreted by Vero cells into the media. Repeated addition of trypsin to the culture medium of influenza virus-infected Vero cells restores the multicycle growth pattern of influenza A virus strains, allowing high yields to be obtained at a low multiplicity of infection. These findings may permit efficient use of Vero (WHO) cells in the production of influenza vaccines. PMID- 7884928 TI - Identification of two separable modules in the duck hepatitis B virus core protein. AB - Hepadnavirus replication requires the concerted action of the polymerase and core proteins to ensure packaging of the RNA pregenome and DNA maturation. The arginine-rich C terminus of the core protein plays an essential role in both of these steps while being dispensable for nucleocapsid formation. In an attempt to identify other functional domains of the core protein, we performed a series of trans-complementation experiments analyzing the ability of duck and human hepatitis B virus (DHBV and HBV) core protein subunits to support the replication of a core-defective DHBV genome. Plasmids expressing the N-terminal amino acids 1 to 67 or the remaining C-terminal portion, amino acids 67 to 262, of the DHBV core protein were cotransfected into LMH cells along with a replication-deficient construct coding for the DHBV pregenome and polymerase. Neither the N nor the C terminus alone yielded replication-competent core particles. However, cotransfection of plasmids that separately expressed both regions restored a normal replication pattern. Furthermore, the DHBV C terminus but not the N terminus could be replaced by the corresponding domain of the HBV core protein in this assay. Finally, coexpression of the complete HBV core protein and the N terminus from DHBV resulted in DHBV replication, while the HBV core protein alone was not functional. Taken together, these findings suggest a modular organization of the DHBV core protein in which the C terminus is functionally conserved among different hepadnaviruses. PMID- 7884929 TI - Sequence diversity of V1 and V2 domains of gp120 from human immunodeficiency virus type 1: lack of correlation with viral phenotype. AB - We analyzed by PCR and direct sequencing 57 viral sequences from 47 individuals infected with human immunodeficiency virus type 1, focussing on the V1 and V2 regions of gp120. There was extensive length polymorphism in the V1 region, which rendered sequence alignment difficult. The V2 hypervariable locus also displayed considerable length variations, whereas flanking regions were relatively conserved. Two-thirds of the amino acid residues in these flanking regions were highly conserved (> 80%), presumably reflecting their critical contribution to V2 structure or function. We also characterized the syncytium-inducing properties of the isolates from which we derived sequence information. There was no correlation between V1 or V2 sequences and the viral phenotype, contrary to a previous report (M. Groenink, R. A. M. Fouchier, S. Broersen, C. H. Baker, M. Koot, A. B. van't Wout, H. G. Huisman, F. Miedema, M. Tersmette, and H. Schuitemaker, Science 260:1513-1516, 1993). The sequence heterogeneity described in this study provides information to suggest that it would be most difficult to exploit the V1 and V2 domains for vaccine development. PMID- 7884931 TI - Requirements for the self-directed replication of flock house virus RNA 1. PMID- 7884932 TI - New multidisciplinary working group focuses on presidential disability. PMID- 7884930 TI - Papilloma formation in human foreskin xenografts after inoculation of human papillomavirus type 16 DNA. AB - A mouse model of high-risk human papillomavirus infection was developed in which human papillomavirus (HPV) type 16 DNA was inoculated into human foreskin grafted to the skin of severe combined immunodeficient (scid) mice. Grafted skin contained human epidermis and dermis and, like normal human skin, expressed involucrin in differentiating keratinocytes. HPV type 16 DNA, attached to gold particles, was delivered directly into human epidermal cells and induced exophytic papilloma with histologic features of papillomavirus infection, including koilocytosis and expression of papillomavirus capsid antigen. This model should be useful for determining in vivo the functions of viral genes and for developing strategies to prevent and treat HPV-associated disease. It may also be of value in developing animal models of other human skin diseases. PMID- 7884933 TI - Hepatitis A vaccine set for 2-year-olds to adults. PMID- 7884934 TI - Religious investors ask health/hygiene products giant to 'kleen' out of the tobacco business. PMID- 7884935 TI - Home testing kits for HIV apt to get FDA approval. PMID- 7884936 TI - Marine rear guard escapes serious injury while covering UN evacuation from Somalia. PMID- 7884937 TI - Crucial antibody response. PMID- 7884938 TI - Lessons from cat virus. PMID- 7884939 TI - From the Centers for Disease Control and Prevention. Exposure of passengers and flight crew to Mycobacterium tuberculosis on commercial aircraft, 1992-1995. PMID- 7884940 TI - From the Centers for Disease Control and Prevention. Ostrich fern poisoning--New York and western Canada, 1994. PMID- 7884941 TI - A piece of my mind. Watchers. PMID- 7884942 TI - What is balance in the physician workforce? PMID- 7884943 TI - Drug-resistant tuberculosis: inconsistent results of pyrazinamide susceptibility testing. PMID- 7884944 TI - Sensitivity of rapid antigen detection tests for Chlamydia trachomatis screening. PMID- 7884945 TI - Essential vs discretionary health care in system reform. PMID- 7884946 TI - Legislating tobacco use: are subsidies hypocritical? PMID- 7884947 TI - Control of Hantavirus in the west. PMID- 7884948 TI - Acute epiglottitis in adults. PMID- 7884949 TI - Caring for the chronically mentally ill. PMID- 7884950 TI - Costs and effects of long-term oral anticoagulant treatment after myocardial infarction. AB - OBJECTIVE: To investigate the costs and effects of long-term oral anticoagulant treatment after myocardial infarction. DESIGN: Cost-effectiveness analysis, based on a randomized, double-blind, placebo-controlled trial. SETTING: Sixty Dutch hospitals. PATIENTS: A total of 3404 hospital survivors of acute myocardial infarction randomized within a median period of 4 days after discharge to either oral anticoagulant treatment or placebo. The mean follow-up was 37 months. INTERVENTION: Oral anticoagulant treatment aimed at a target international normalized ratio of 2.8 to 4.8. MAIN OUTCOME MEASUREMENTS: Costs of hospital stay during readmissions, costs related to major cardiologic interventions, and costs of oral anticoagulant treatment. RESULTS: The costs of oral anticoagulant treatment were estimated at 394 Dutch guilders (Dfl) per patient-year (Dfl 1 = US $0.58). Placebo patients stayed 18,830 days in the hospital compared with 15,083 days for anticoagulation patients. Average costs per patient of medical care during follow-up were estimated at Dfl 10,784 for placebo patients and Dfl 9878 for anticoagulation patients. CONCLUSIONS: Costs of long-term anticoagulant treatment are outweighed by the costs of prevented clinical events. PMID- 7884951 TI - An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial. AB - OBJECTIVE: To test the hypothesis that ibuprofen increases the risk of hospitalization for gastrointestinal bleeding, renal failure, or anaphylaxis among febrile children. DESIGN: Randomized double-blind acetaminophen-controlled trial. SETTING: Outpatient pediatric and family medicine practices. PATIENTS: A total of 84,192 children. INTERVENTION: Patients were randomly assigned to receive 12 mg/kg of acetaminophen, 5 mg/kg of ibuprofen, or 10 mg/kg of ibuprofen. MAIN OUTCOME MEASURES: Hospitalizations for acute gastrointestinal bleeding, acute renal failure, and anaphylaxis. RESULTS: A total of 277 patients (0.3%) were unavailable for follow-up. Overall, 795 participants (1%) were hospitalized, primarily for infectious diseases; hospitalization rates did not differ according to treatment group. Four children had diagnoses of acute, nonmajor gastrointestinal bleeding (two in each ibuprofen dosage group); among ibuprofen-treated children, the observed risk of gastrointestinal bleeding, 7.2 per 100,000 (95% confidence interval, 2 to 18 per 100,000), was not significantly different from the risk among acetaminophen-treated children (P = .31). There were no hospitalizations for acute renal failure or anaphylaxis; the upper 95% confidence bound for the risk of either of these outcomes was 5.4 per 100,000 ibuprofen-treated children. Among a number of other possibly serious adverse drug events, low white blood cell count was marginally associated with ibuprofen treatment. Because this association was observed in the setting of multiple comparisons and white blood cell counts may have been low before treatment, causation is unclear. CONCLUSIONS: The risk of hospitalization for gastrointestinal bleeding, renal failure, or anaphylaxis was not increased following short-term use of ibuprofen in children. These data, however, provide no information on the risks of less severe outcomes or the risks of prolonged ibuprofen use. PMID- 7884952 TI - Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group. AB - OBJECTIVE: To evaluate the efficacy and safety of anti-tumor necrosis factor alpha monoclonal antibody (TNF-alpha MAb) in the treatment of patients with sepsis syndrome. DESIGN: Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial. SETTING: A total of 31 hospitals in the United States and Canada. PATIENTS: There were 994 patients with sepsis syndrome enrolled in this clinical trial, and 971 patients were infused with the study drug. INTERVENTION: Patients were prospectively stratified into shock or nonshock groups and then randomized to receive a single infusion of 15 mg/kg of TNF-alpha MAb, 7.5 mg/kg of TNF-alpha MAb, or placebo. Patients received standard aggressive medical and surgical care during the 28-day postinfusion period. OUTCOME MEASURE: Twenty-eight-day all-cause mortality. RESULTS: The distribution of variables describing demographics, organ system dysfunction or failure, preinfusion Acute Physiology and Chronic Health Evaluation II score, number of organs failing at baseline, initial sites of infection, infecting microorganisms, antimicrobials used, and initial invasive procedures was similar among patients in the TNF-alpha MAb and placebo treatment arms. Among all infused patients, there was no difference in all-cause mortality in patients who received placebo as compared with those who received TNF-alpha MAb. In septic patients with shock (n = 478), there was a trend toward a reduction in all-cause mortality, which was most evident 3 days after infusion: 25 of 162 patients treated with 15 mg/kg of TNF-alpha MAb died, 22 of 156 patients treated with 7.5 mg/kg of TNF-alpha MAb died, and 44 of 160 patients in the placebo group died (15 mg/kg: 44% reduction vs placebo, P = .01; 7.5 mg/kg: 48.7% reduction vs placebo, P = .004). At day 28, the reduction in mortality for shock patients was not significant for either dose of TNF-alpha MAb relative to placebo (15 mg/kg, 61 deaths among 162 patients [37.7% mortality]; 7.5 mg/kg, 59 deaths among 156 patients [37.8% mortality]; placebo, 73 deaths among 160 patients [45.6% mortality]; P = .20 for 7.5 mg/kg and P = .15 for 15 mg/kg). Serious adverse events were reported in 4.6% of all infused patients. No immediate hypersensitivity allergic reactions due to TNF alpha MAb were reported. Serum sickness-like reactions were seen in 2.5% of patients receiving TNF-alpha MAb. CONCLUSIONS: There was no decrease in mortality between placebo and TNF-alpha MAb in all infused patients. In septic shock patients who received TNF-alpha MAb, a significant reduction in mortality was present 3 days after infusion. Although a trend toward reduced mortality continued at 28 days following treatment with TNF-alpha MAb, the difference in mortality among shock patients treated with placebo or TNF-alpha MAb was not significant. PMID- 7884953 TI - Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. AB - OBJECTIVE: Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 allele (APOE epsilon 4) is a risk factor for familial AD. To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. We also compared them with seven patients with probable AD. DESIGN: After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups. SETTING: University medical center. PATIENTS: At risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with APOE epsilon 4 did not differ from those without APOE epsilon 4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3). MAIN OUTCOME MEASURES: Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18. RESULTS: Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 compared with those without APOE epsilon 4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4. CONCLUSIONS: These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in non-demented relatives at risk for probable AD. Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder. PMID- 7884954 TI - Safe water treatment and storage in the home. A practical new strategy to prevent waterborne disease. AB - In many parts of the developing world, drinking water is collected from unsafe surface sources outside the home and is then held in household storage vessels. Drinking water may be contaminated at the source or during storage; strategies to reduce waterborne disease transmission must safeguard against both events. We describe a two-component prevention strategy, which allows an individual to disinfect drinking water immediately after collection (point-of-use disinfection) and then to store the water in narrow-mouthed, closed vessels designed to prevent recontamination (safe storage). New disinfectant generators and better storage vessel designs make this strategy practical and inexpensive. This approach empowers households and communities that lack potable water to protect themselves against a variety of waterborne pathogens and has the potential to decrease the incidence of waterborne diarrheal disease. PMID- 7884955 TI - Prevalence of hepatitis B markers and measles, mumps, and rubella antibodies among Jewish refugees from the former Soviet Union. AB - OBJECTIVE: To assess the prevalence of hepatitis B virus (HBV) infection and immunity to measles, mumps, and rubella among refugees from the former Soviet Union (FSU). DESIGN: Descriptive study. SETTING: Soviet Immigrant Health Care Program, Sinai Samaritan Hospital, Milwaukee, Wis. PATIENTS: Consecutive sample of 496 Jewish refugees from the FSU presenting for new arrival screening from December 1, 1990, through January 11, 1993. OUTCOME MEASURES: Hepatitis B surface antigen (HBsAg), hepatitis B core antibody, hepatitis B surface antibody, and measles, mumps, and rubella antibodies. RESULTS: At least one hepatitis B marker was detected in 22% of the refugees, and HBsAg was detected in 0.4%. The rate of HBV infection (any marker present) increased with increasing age, ranging from 4% among those aged 0 through 19 years to 31% among those aged 50 through 59 years (chi 2 test for trend, 13.5; P < .001). Among those aged 0 through 19 years, 19% lacked antibody to measles, 8% lacked antibody to mumps, and 13% lacked antibody to rubella. Refugees who were less than 30 years of age were more than twice as likely to lack antibodies to measles, mumps, or rubella compared with those who were 30 years of age or older (relative risk, 2.8; 95% confidence interval, 1.8 to 4.2; P < .001). CONCLUSIONS: In our sample of Jewish refugees from the FSU (primarily Ukraine, Russia, and Belorussia), the rate of HBsAg positivity was low, suggesting that routine screening for HBV infection is not needed. Seronegativity to measles, mumps, and rubella was relatively common among those less than 30 years old. Those refugees who were born after 1957 should be given combined measles, mumps, and rubella vaccine unless their written documentation indicates previous receipt of these antigens according to the immunization schedule recommended in the United States. PMID- 7884956 TI - Antibiotics in chronic obstructive pulmonary disease exacerbations. A meta analysis. AB - OBJECTIVE: A meta-analysis of randomized trials was performed to estimate the effectiveness of antibiotics in treating exacerbations of chronic obstructive pulmonary disease (COPD). DATA SOURCES: English-language studies published from 1955 through 1994 were retrieved using MEDLINE, Index Medicus, bibliographies, and consultation with experts. MEDLINE search terms included "COPD," "chronic bronchitis," and "antibiotic(s)." STUDY SELECTION: Only randomized trials that enrolled patients having an exacerbation of COPD, used an antibiotic in the treatment group and placebo in the control group, and provided sufficient data to calculate an effect size were included in the meta-analysis. DATA EXTRACTION: Descriptive and outcome data from each study were independently in the meta analysis. DATA SYNTHESIS: Overall summary effect size of the nine trials satisfying all inclusion criteria was 0.22 (95% confidence interval [CI], 0.10 to 0.34), indicating a small benefit in the antibiotic-treated group. Similar analysis of the six studies that provided data on peak expiratory flow rate changes revealed a summary effect size of 0.19 (95% CI, 0.03 to 0.35) and a summary change in peak expiratory flow rate of 10.75 L/min (95% CI, 4.96 to 16.54 L/min) in favor of the antibiotic-treated group. Sensitivity analyses did not significantly affect these results. CONCLUSIONS: These analyses suggest a small but statistically significant improvement due to antibiotic therapy in patients with exacerbations of COPD. This antibiotic-associated improvement may be clinically significant, especially in patients with low baseline flow rates. PMID- 7884957 TI - My career as a radioisotope hunter. PMID- 7884958 TI - Economics and efficacy in choosing oral anticoagulants or aspirin after myocardial infarction. PMID- 7884959 TI - Another word of caution regarding a new long-acting bronchodilator. PMID- 7884960 TI - [Rheumatoid factor and cryoglobulin are not efficiently related to cold activation of complement]. AB - Cold activation of complement (CA) is a phenomenon characterized by a low hemolytic complement activity in chilled serum. Cryoglobulin and RF have been reported as main causes of CA, and we previously reported the close association between CA and HCV infection in 21 CA patients. Therefore, we assayed CA, RF, cryoglobulin and anti-HCV antibody titers in 304 randomly selected patients with unknown diseases. CA was positive in 26 of the 304 patients, and among them, RF and/or cryoglobulin were found positive in 20 patients, and anti-HCV antibody were positive in all of them. RF was positive in 41 of the 304 patients. 37% of them were anti-HCV antibody positive and 63% were negative. Cryoglobulin was positive in 61 out of 304 patients. Anti-HCV antibody positivity was observed in 59 out of 304 patients, and all CA-positive cases were included in the anti-HCV antibody-titer-positive group. However, either RF or cryoglobulin positive patients were observed in the same degree in both anti-HCV antibody titer positive and negative groups. Therefore, RF or cryoglobulin is not considered the main cause of CA. PMID- 7884961 TI - [Acute myocardial infarction without elevation of CK activity: analysis of CK-MM protein and gene of CK-MM]. AB - A 56 year old female patient had acute myocardial infarction which was confirmed by autopsy. However the patient showed no elevation of CK activity in the serum. We proved the deficiency of CK-MM protein in her serum as well as in the myocardial tissues. To further elucidate the molecular mechanism we isolated and characterized genomic DNA and cDNA of CK-MM from the myocardial tissue of the patient and demonstrated the depression of mRNA of CK-MM which might be related with the deficiency of CK-MM protein. Point mutation at codon 54 [Exon 2, GAC (Asp)-->GGC(Gly)] was also demonstrated on the beta-sheet of CK-MM. Association of point mutation with depressed CK-MM is to be clarified. PMID- 7884962 TI - [Laboratory tests using genes]. AB - Gene diagnosis has been introduced into clinical laboratories these several years. After the initial phase of confusion, the technique has settled to play an indispensable role in clinical medicine. Both exogenous and endogenous pathogens are currently the target of gene diagnosis. Recently, the use of PCR (polymerase chain reaction) technique broadened remarkably the applicability of genes to diagnosis of various diseases. Along with this wider use of gene diagnosis, several new problems have emerged to be solved in near future. As examples of gene diagnosis, analyses of MRSA mecA gene and Alzheimer's disease genes are presented. PMID- 7884963 TI - [Digoxin concentration in blood]. AB - Immunoreactive digoxin-like activity was found in the Chinese medicine, KYUSHIN tablet, taken popularly in Japan without prescription. The antibodies used in the assays of digoxin reacted with Ch'an-su, the major effective component of KYUSHIN, which contained cardiotonic steroids with a chemical structure similar to that of digoxin. One tablet of KYUSHIN had digoxin-like immunoreactivity equivalent to 1.9 micrograms. (TDx analyzer), 1.5 micrograms (Du Pont aca analyzer) and 72 micrograms digoxin (Enzymun-Test, Boehringer). These different equivalencies may be attributed to differences in cross-reactivity of the antibody used in the immunoassays. Two healthy volunteers took two KYUSHIN tablets three times a day, a typical dose, and digoxin-like immunoreactivity reached almost 0.4 microgram/l in 0.5 day. Recently, a competitive digoxin chemiluminescent immunoassay has been developed by Ciba Corning ACS 180. The assay utilizes an acridinium-ester labelled mouse monoclonal digoxin antibody as the tracer. In the extracted solution of KYUSHIN and serum after administration of two tablets, the digoxin-like immunoreactivity value on the Ciba Corning ACS 180 digoxin assay was < 0.10 microgram/l (off-range low). Therapeutic drug monitoring should be interpreted carefully in patients taking Chinese medicines, many of which contain the Ch'an-su component. PMID- 7884964 TI - [An assay by electron spin resonance spectrometer and its medical applications]. PMID- 7884965 TI - [Rearrangement of the c-erbB2 oncogene--analysis of the gastrocolic carcinoma]. AB - We analyzed amplification, rearrangement and point mutation of the c-erbB2 oncogene about 10 cases of the stomach cancer and 30 cases of the colon cancer. Rearrangement and amplification of the c-erbB2 oncogene were found in one case of moderately differentiated tubular adenocarcinoma of the stomach. According to the restriction map, the rearrangement apparently occurred in the region from the 5' promotor to the extracellular domain. In this case, it appeared that the over expression of ErbB2 oncoprotein detected by immunohistochemical staining was associated with rearrangement of the gene. Thus it was suggested that the point mutation of the transmembrane domain, which has been demonstrated in the rat protooncogene neu, a homolog of human c-erbB2, was not detected in this case. PMID- 7884966 TI - [Frequency of genetic polymorphism (Arg353-->Gln) and factor VII levels in Japanese healthy adults]. AB - We studied factor VII levels and frequency for a G-to-A substitution resulting in the replacement of glutamine for arginine at codon 353 of factor VII by Msp I polymorphism in 101 Japanese healthy adults. An homozygote and seven heterozygotes for the factor VII Gln 353 allele was found in the samples. The frequency of Japanese was not different from those of populations of the United Kingdom, Europe and Afro-Caribbeans, but was different from that in Gurjarati Indians (0.25) previously reported by Humphries et al (Arch Pathol Lab Med 116:1322-1329, 1992). The homozygote had the lowest levels (factor VII activity; 50% and factor VII antigen; 45%) in all samples. The seven heterozygotes had levels of factor VII activity and factor VII antigen about 25% lower than those with only the arginine allele. There were no difference in the levels of factor VII between smoking and no smoking heterozygotes, and between those taking fatty and non-fatty diet. PMID- 7884967 TI - [DNA polymorphisms in strains of Staphylococcus aureus. I. Usefulness of coagulase gene as an epidemiological marker]. AB - In this study, we report the genotyping of Staphylococcus aureus by restriction enzyme digestion of the nested PCR products of coagulase gene from clinical strains of 83 MRSA (methicillin-resistant S. aureus) and 23 MSSA (methicillin sensitive S. aureus). Using Alu I restriction enzyme, a total of 106 strains could be classified into 19 different restriction patterns, arbitrarily designated the genotypes 1 to 19 for strains. The DNA patterns of the PCR coagulase gene products were visualized by ethidium bromide after 2% agarose gel electrophoresis and hybridized with alkaline-phosphatase labeled probe. Because of unique sequences of the coagulase gene containing 81-bp tandem repeats and Alu I recognition sites, most of clinical strains had bands in multiples of 81 bp which allowed easy discrimination among isolates. The deduced DNA fragment sizes ranged from approximately 80 to 900 bp, and the numbers of DNA fragments generated were 2 to 9. Eighteen of the 20 MRSA strains taken from the patients hospitalized in 1991 belonged to the genotypes 2 and 3, and 27 of the 29 MRSA strains taken from patients in 1992 belonged to the genotypes 1, 2 and 3, suggesting the possibility of nosocomial outbreaks caused by these strains. In conclusion, this coagulase gene restriction fragment length polymorphism (RFLP) technique will be useful for epidemiological evaluations of nosocomial MRSA infections. PMID- 7884968 TI - [Detection of human cytomegalovirus DNA by nested polymerase chain reaction]. AB - Detection of human cytomegalovirus (CMV) DNA from peripheral blood and urine specimens taken from renal transplant and bone marrow transplant recipients was examined by using nested polymerase chain reaction (PCR). Results by the PCR were compared with those of healthy subjects. Oligonucleotide primers were used to amplify the immediate-early (IE) and the late antigen (V) genes of CMV. Amplified DNA products were identified by 2% agarose gel electrophoresis and by Southern hybridization with alkaline phosphatase-labeled probes. Twenty eight blood specimens from 118 healthy subjects were positive for the V gene fragment of CMV, whereas the IE gene fragment was more associated with a negative result (116 of 118 specimens). When amplified with mixed primer pairs, no blood and urine specimens simultaneously produced the PCR products of two separate CMV genes. In the case of transplant patients, however, 50 of 139 blood specimens and 34 of 117 urine specimens were positive with the V primers, and 23 blood and 17 urine specimens were positive with the IE primers. Using mixed primer pairs, amplification of two CMV genes was detected in 14 blood and 10 urine specimens. In three cases of bone marrow transplant recipients, amplification of two CMV genes was detectable prior to anti-CMV IgM development. From these results, we suggest that detection of CMV-DNA by nested PCR with mixed primer pairs may be a valuable tool for diagnosing CMV infections. PMID- 7884969 TI - [Early diagnosis and detection of successful reperfusion by mitochondrial AST/soluble-AST ratio after acute myocardial infarction]. AB - The change of mitochondria aspartate aminotransferase (m-AST)/soluble-AST (s-AST) ratio was examined in 22 cases of acute myocardial infarction (AMI). The m-AST/s AST was 40.8 +/- 18.9% at admission to a hospital (2.9 +/- 1.6h). The m-AST/s-AST decreased to normal value rapidly after peak and then increased again gradually. The decrease ratio of m-AST/s-AST per minute at early stage of 8 cases, who were succeeded to reperfusion, was 0.28 +/- 0.20%, and that was significantly higher than of conventionally treated 7 cases and non-reperfused 7 cases (0.11 +/- 0.07%). These results indicated that (1) m-AST/s-AST may be an excellent indicator for AMI in early stage. (2) The decrease ratio of m-AST/s-AST would predict whether reperfusion is successful or not at an earlier stage of AMI. PMID- 7884970 TI - [Applications of mass spectrometry for clinical laboratory test]. AB - Mass spectrometry (MS) has recently played a considerable role in the chemical measurements in clinical laboratories. We have analyzed organic acids for diagnosis of organic acidemias, and tried to report quantitative data measured by GC/MS with 20 kinds of standard compounds of key metabolites labelled with stable isotopes. By ESI/MS/MS acylcarnitine was analyzed accurately and quickly. We found a new acylcarnitine compound in urine from a patient with multiple carboxylase deficiency, which showed m/z 276 ion peak on the spectrum by precursor ion scan of methylated compounds of dried raw urine. This was identified as 3-hydroxyisovalerylcarnitine. By ESI/MS, hemolysate was analyzed and an ion peak of abnormal alpha subunit of hemoglobulin, Hb MBoston, was clearly separated from the normal alpha subunit. Serum transferrin precipitated with anti-transferrin serum was analyzed by MALDI/TOF/MS. The transferrin antibody complex in the immunoprecipitates was separated into transferrin and IgG in an acidic pH, which is the usual condition of loading on MALDI/TOF/MS. Ions of IgG and other minor components were not superimposed on the transferrin ions. Transferrin isoform with a molecular weight about 2.2kDa smaller than normal transferrin, which is contained in the serum from patients with carbohydrate deficient glycoprotein syndrome, was identified by this method. The MALDI/TOF/MS analysis of immunoprecipitates may serve as a simple and sensitive method to identify the molecular weight heterogeneity of various biological materials. PMID- 7884971 TI - [Tibial nerve somatosensory evoked potentials: studies on latency variability as a function of subject height and age]. AB - Scalp-recorded somatosensory evoked potentials (SEP) to posterior tibial nerve stimulation were studied in healthy volunteers (27 males and 25 females) aged 15 67 years. Age alone was not correlated with SEP latencies, except for P 60 latency, but multiple regression analysis with two independent variables (height and age) showed that not only height but also age is a significant parameter in determining the optimal clinical limits for individual SEP latencies, and may increase the diagnostic sensitivity of absolute SEP latencies. There was no gender difference in the latencies of SEP in multiple correlation analysis involving height and age. A negative correlation tended to be found between height and age in adult subjects, although this is thought to be a characteristic of Japanese, it may show the necessity of renewing regression models at intervals of 5 or 10 years. PMID- 7884972 TI - [REN plot for a graphic expression method of clinical laboratory data statistics]. AB - Laboratory data have been processed statistically on an assumption that they formed a normal distribution curve by themselves or after their transformation. The data of clinical medicine, however, frequently form distributions different from the normal one and thus they are not exactly represented by simple statistics such as mean and standard deviation. We used non-parametric percentiles(pct) as parameters for an improved expression of data distributions. The parameters used in this method are as follows: mean, 50 pct as median, 25 and 75pct as a concentration indicator, 5 and 95pct as a 90 percent central range, 2.5 and 97.5pct as a 95 percent central range, and minimum and maximum data as a distribution range. These indicators were presented on a new form of box-and whisker plot. This expression was named as REN plot. Our method was compared to the other statistical expression methods using the data of control surveys of Factor IX activity of normal plasmas and prothrombin time of abnormal standard plasmas as well as APTT of abnormal plasma measured for intra-laboratory quality control. It was found that any form of data distribution, normal or abnormal, was precisely expressed in detail and the gradient of data densities were visually plotted by our method. Also neither the median, central range nor distribution range was influenced by extreme values. It was concluded that REN plot was useful expression for the statistical analysis of clinical laboratory data. PMID- 7884973 TI - [Working memory capacity related to reading: measurement with the Japanese version of reading span test]. AB - The efficiency of working memory capacity was measured with the Japanese reading span test (Japanese RST), which was developed based on the Carnegie-Mellon RST (Daneman & Carpenter, 1980). The correlation between the Japanese and the CMU RST was found to be highly significant. The present Japanese RST seems to predict reading efficiency in the same way as does the CMU RST. The Japanese RST was found to be correlated not only with memory span but with reading comprehension. However, it was not correlated with existing verbal intelligence tests. PMID- 7884974 TI - [Minority versus majority: intergroup discrimination in the minimal group paradigm]. AB - The present study was conducted to investigate the intergroup behaviour from the perspective of social identity theory. It was predicted that (a) when group membership was based on trivial categorization (e.g., by drawing lots), minority group members would be more conscious of their social identity, and favour their own group more in reward distribution than majority group members; (b) when based on value-loaded categorization (e.g., by social attitudes), both minority group and majority group members would favour their own group; (c) both minority group and majority group members would perceive converted members, who move away from their initial attitudes, as a threat to their social identity, and discriminate them. Results from three experiments under the minimal group paradigm, with undergraduate students, supported these predictions. Findings were discussed in terms of salience of social identity in categorization of minority versus majority, and the impact of anonymity in the minimal group paradigm. They were also discussed to compare the theory with belief congruence theory, which argues that attraction due to similarity of belief is the cause of ingroup favoritism. PMID- 7884975 TI - [The effect of changes in interpersonal closeness on person perception]. AB - The purpose of this study was to investigate changes in person perception due to changes in interpersonal closeness. Immediately after beginning the first semester, four female university freshmen belonging to a student club were asked: 1) to tell what they thought of or knew about three fellow club members (stimulus persons; SPs); and 2) to indicate liking for SPs, and rate them in terms of factors related to interpersonal attraction. The interviews, with the same interviewees and SPs, were repeated seven more times during the following six months. Content of their statements for each SP was analyzed, and results indicated: 1) Liking for SPs was positively correlated with the frequency of statements concerning SPs' disposition, but negatively with that of SP's objective information; 2) the more distant the subject-SP relationship became after initial closeness, the more the frequency of statements about SP's objective information, and the less that of SPs' disposition. It was suggested that self-other relationship had an effect on person perception. PMID- 7884976 TI - [Effects of goals and perceived probabilities of goal attainment on self assessment]. AB - This study examined effects of explicitness of achievement goals and perceived probabilities of goal attainment on self-assessment. Subjects were 251 undergraduate students. They were first asked, as measure of explicitness of goals, if they hope to acquire good capability in scientific research, and second how they perceived their probabilities of goal attainment. Self-assessment behavior was measured by task choice and task preference for four tasks which differ in diagnosticity. The main results were as follows. (a) The most diagnostic task was chosen more often by the subjects who both had an explicit goal and perceived the probability of goal attainment high, and those who didn't have an explicit goal and perceived the probability low. (b) On task preference, the effects of goal explicitness and perceived probability were not found. These results suggest that self-assessment be done for future self-enhancement. PMID- 7884977 TI - [The effect of observational goals on observation of ongoing behavior of other]. AB - The study investigated the effect of observational goals (i.e., impression formation and memory) on the process of observing ongoing behavior of others. Specifically, the amount of behavior extraction was studied. Forty-nine subjects were randomly assigned to impression and memory groups, and asked to watch a ten minute video clip featuring a male actor in daily activities. The subjects in the impression group were instructed to press a button when they saw an impression relevant action and to release it when it was over. Similarly, the subjects in the memory group were instructed to press the button when a memory-relevant action appeared and to release it when it came to an end. Results showed that the memory subjects extracted actions more frequently and in longer duration than the impression subjects. Furthermore, the memory subjects recalled more behaviors than the impression subjects, whereas the latter subjects used more personality trait descriptions than the former. PMID- 7884978 TI - [Advances in the experimental analysis of behavior: issues of choice behavior, comparative cognition, and human language]. AB - As the opportunity to contact with related areas has increased, the study of of the experimental analysis of behavior has experienced revolutionary changes. Some of the most active and important areas-studies of choice, comparative cognition, and human language--are reviewed to acquaint readers. Studies of CHOICE have linked to the molar theories of behavioral economics and behavioral ecology, which promoted research of choice by animals under uncertainty conditions. Further approach has been made to integrate the molar and molecular analyses on the basis of the ideas of behavior dynamics. COMPARATIVE COGNITION is a part of a larger field including cognitive science, behavioral neuroscience, and biological science. Recent developments, aided with a comparative perspective, made significant contributions to our understanding of the phylogeny and ontogeny of cognition. Advances in analysis of human behavior provided tools to study behavioral aspects of semantics, syntax, and pragmatics of HUMAN LANGUAGE. Using the paradigm of stimulus equivalence, the emergence of stimulus relations, stimulus-stimulus networks, hierarchical structure of verbal behavior, and other language-related behaviors have been investigated. PMID- 7884979 TI - Birth-related neurological injury compensation programs. PMID- 7884980 TI - Bringing medical informatics into mainstream clinical medicine. PMID- 7884981 TI - E. coli O157:H7 in Kansas, January 1993 to September 1994. PMID- 7884982 TI - Advances in the management of voice disorders. PMID- 7884983 TI - Geriatric ethics: justifying paternalism. PMID- 7884984 TI - Physicians are key to breast cancer early detection. PMID- 7884985 TI - [Does nocturnal hypoxia relate to acute exacerbation of chronic respiratory failure with right heart failure in late sequelae of pulmonary tuberculosis?]. AB - Thirty-eight patients with late sequelae of pulmonary tuberculosis (TB seq.) were studied to clarify whether or not nocturnal oxyhemoglobin desaturation (NOD) could relate to acute exacerbation of chronic respiratory failure (AE). All patients had been untreated with home oxygen therapy, because they were not severely hypoxic. We performed sleep studies, pulmonary function tests and arterial blood gas analysis and investigated past history about AE in each patient. Twelve patients had experienced AE with right heart failure and they were classified as CHF (congestive heart failure) group. The rest was classified as Non-CHF group. These two groups were compared as for each variables examined. There was no difference between the two groups in age, body weight, %VC, FEV1.0%, and awake PaO2. Awake PaCO2 was significantly higher in CHF group. Although no difference was observed in baseline SaO2, the degree of NOD was significantly greater in CHF group when evaluated by lowest SaO2 during sleep and 85% desaturation time (total time spent with SaO2 less than 85%). Moreover, 21 of Non CHF and 6 of CHF were studied for cardiac parameters using right side cardiac catherization. While the differences of mean pulmonary arterial pressure and cardiac output between the two groups were not significant, pulmonary arteriolar resistance was higher in CHF group. We concluded that NOD in TB seq. had a major role in AE with right heart failure. We speculated that AE might be caused, at least partly, by pulmonary vasopressor response to recurrent NOD. PMID- 7884986 TI - [Shortening of hospitalization period for patients with pulmonary tuberculosis]. AB - The development of specific chemotherapeutic agents revolutionally improved the prognosis of tuberculosis and markedly shortened the duration of the treatment. Evidence of successful treatment with short-course regimens for pulmonary tuberculosis has been accumulated. But, the duration of hospitalization tends to be determined empirically and varys among hospitals and clinicians. Generally speaking, the duration of hospitalization is longer in Japan than in the United States and Europian countries. We investigated retrospectively the duration of hospitalization, treatment period, and recurrence rate of the disease for patients with pulmonary tuberculosis who admitted to the Tokyo Metropolitan Fuchu Hospital in the years 1984, 1988, and 1991. Patients who had been previously treated for more than 2 weeks and/or, had severe complications, such as malignancy and miliary tuberculosis were excluded from the study. Cases who died during the hospitalization and discharged without permission were also excluded. Numbers of subjects in each year were 114, 114, and 115 in 1984, 1988, and 1991, respectively. A total of 343 patients (M: 254, F: 89) were enrolled to the study and their average age was 49.4 yr old. A number of patients with both smear and culture positive in sputum bacteriology was 210 (61.2%), and 42 cases (12.2%) were smear negative and culture positive. The results are as follows: (1) Mean duration of hospitalization in the years 1984, 1988, and 1991 were 141, 102, and 72 days, respectively. That is, a mean hospitalization period was shortened to about half during these seven years. (2) According to the chest x-ray classification (Group A: I, II3, B: II1, II2, III3, C: III1, III2), mean durations of hospitalization were 186 days for group A, 143 days for group B, and 108 days for group C in 1984, and 96 days, 76 days, and 59 days in 1991, respectively. (3) According to sputum bacteriology, mean durations of hospitalization were 169 days for (S+/C+) cases, 105 days for (S-/C+) cases, and 90 days for (S-/C-) cases in 1984, and 83 days, 67 days, and 41 days in 1991, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884987 TI - [A case of Mycobacterium avium disease presenting as a solitary pulmonary nodule and resected under a suspicion of lung cancer]. AB - A 43 year old female smoker was admitted to our hospital for evaluation of solitary pulmonary nodule (SPN). She had no symptoms, and no past history or family history that might suggest compromised defense against pulmonary infections. Physical examination and laboratory findings including humoral and cell-mediated immunity revealed no abnormality. The chest radiography taken 2 years ago looked normal, but those on admission showed SPN in a left lower field. Computed tomography (CT) revealed solitary elipsoid nodule in S5. Because two trials of transbronchial biopsy, brushing and washing could not give any diagnostic findings, thoracotomy was performed under tentative diagnosis of lung cancer. The lesion was located in the outer portion of S5 and was found to consist of 2 elastic hard nodule surrounded by a atelectasis with inflammation. The nodule had supprative substance with several acid fast bacilli, and its intraoperative pathology revealed epitheloid cell granulomas. The lesion was resected completely. In a mean while, seventy smooth colonies grew on an Ogawa egg medium, which was identified as M. avium by the probe analysis using SNAP TEST. The final diagnosis of pulmonary M. avium disease was made, and the patient was administered RFP, EB, OFLX, and CAM in a outpatient clinic. Some discussions were also made about CT findings of pulmonary M. avium complex disease developed in patients without any predisposing conditions. PMID- 7884988 TI - [A case of Mycobacterium fortuitum pulmonary disease in a healthy young woman successfully treated with ciprofloxacin and doxycycline]. AB - A 22 year-old woman was admitted to our hospital complaining of subtle fever and productive cough. She did not smoke and had no underlying disease. Her chest radiograph showed infiltration in the right upper lung field. A diagnosis of Mycobacterium fortuitum pulmonary disease was made on the basis of isolation of M. fortuitum from repeated sputum cultures. On admission, we administered standard antimycobacterial agents, but found the M. fortuitum isolated in this case to be completely resistant to them. We then administered antibiotics including 600 mg of ciprofloxacin and 200 mg of doxycycline. The pneumonic findings on chest X-ray and her clinical symptoms gradually improved thereafter. The in vitro susceptibility tests confirmed the efficacy of ciprofloxacin and doxycycline. We concluded that these drugs contributed significantly to improve the disease. PMID- 7884989 TI - [The estimates of the future trend of tuberculosis incidence and the control programs for its elimination]. AB - In most European and other industrialized countries, it is estimated that tuberculosis would be eliminated around 2030, and in the U.S. and Western European countries, new tuberculosis strategies were developed to eliminate tuberculosis. The Ministry of Health and Welfare (MOHW) in Japan too, has also introduced some new tuberculosis control plans and goals. In Japan, it is estimated that the elimination of tuberculosis would be achieved around 2060, and MOHW has set the final goal for the elimination of tuberculosis by the year 2030. MOHW has also set two interim goals by the year 2000, i.e., (1) to achieve the tuberculosis incidence of below 20 per 100,000 population, (2) to achieve the tuberculosis incidence in children to the level of elimination, that is below 0.1 per 100,000. Wishing the success of these plans, the author tried to examine the possibility of achieving the goals by 2000. The decline of tuberculosis incidence rate in Japan has been gradually slower since 1977. However, the declining trend has become almost constant since around 1983, although it is still very slowly decreasing. Therefore, assuming that the future incidence rates will continue at the same decreasing speed as that of average annual decline rate during the last 10-year period from 1983 to 1992, the incidence rate in Japan in 2000 would be estimated to become 30.9 per 100,000 (95% C.I.; 29.8-31.7), and the incidence rate in children would be 0.87 per 100,000 (95% C.I.; 0.71-1.05). Examining the possibility of acceleration of the declining speed of tuberculosis incidence, it was discussed that there could be a possibility of removing such cases as the preventable cases, non-tuberculosis and inactive tuberculosis cases from newly registered cases in advance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884990 TI - [The present condition of patient's, doctor's and total delays in tuberculosis case-finding and countermeasures in the future]. AB - The incidence of tuberculosis has reduced in Japan, but the slowing down in the rate of decrease of the incidence was pointed, and this tendency is a severe problem in the tuberculosis control. Tuberculosis is considered as a disease of the past, and patient's delay and doctor's delay have gotten very long. The risk of infection with other people is on the increase, consequently, that is one of the causes of the slowing down in the rate of decrease of the incidence. The purpose of this study is clearing up the problems of patient's and doctor's delay, investigating 1274 patients diagnosed as pulmonary tuberculosis in our hospital for five years. In the cases detected their symptomatic visit and received primary treatment of tuberculosis, the alive cases, when they released from our hospital, were 584 cases. In the cases, some cases, who went to a hospital soon after they felt some symptoms, tended to not be diagnosed as pulmonary tuberculosis in their early stage. Other cases, who didn't go to a hospital until they had severe symptoms, tended to be diagnosed as pulmonary tuberculosis promptly. So, finally, total delay tended to be very long. We pointed out some cases, who detected by health check and neglected their visit to any hospitals, and after long times, went to hospitals with symptoms. They were the source of pulmonary tuberculosis to other people. And they didn't have sufficient family contact examination. In the dead cases, 47 cases were died of pulmonary tuberculosis, and their term of hospitalization was very short and their status were extremely severe.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884991 TI - [The current situations and measures in the future in childhood tuberculosis]. AB - We performed a retrospective analysis of 358 patients who were treated for active TB in our hospital from 1976 to 1993. The rate of primary pulmonary tuberculosis was 49.0% and post primary pulmonary tuberculosis was 25.6%. But the rate of tuberculous meningitis and miliary tuberculosis was 7% respectively. Fatal cases of tuberculous meningitis had continued. Seventy-four percent out of 358 patients had a contact history with active tuberculosis. Main source of infection were their father, mother and grandparents. Thirty-two percent of patients had received BCG. Only 12.6% out of the patients under 5 years of age had received BCG. Only nine percent of 23 cases with tuberculous meningitis had received BCG. If the Ministry of Health and Welfare criteria of chemoprophylaxis was indicated rigidly, about 40% of patients who needed chemoprophylaxis in this study would have been overlooked. Indication of chemoprophylaxis should be decided in each patient flexibly. The study of the contact examination showed that two thirds toddler had tuberculosis within two months after detection of source of infection. Thirty percent of the patients in this study were preventable if contact examination and chemoprophylaxis were appropriately done. In the study of drug susceptibility of TB bacilli from 71 patients, 14 strains were resistant to at least one drug. The resistant rate to each drug was higher than adult resistant rate. In order to eliminate childhood TB, the following is necessary: 1) BCG vaccination in the early infancy. 2) prompt and appropriate contact examination and chemoprophylaxis, 3) infection control against drug resistant bacilli. PMID- 7884992 TI - [The examination of tuberculosis contacts: the current situations and perspective in Japan]. AB - Contacts of active tuberculosis cases are the most easily identified high-risk group for tuberculosis in Japan. Thus, examination of the contacts is one of the most useful methods for finding persons with disease or with infection. The purpose of this study is to analyze recent problems in the examination. Program assessment and evaluation for the contact examination were administered by a mail questionnaire to 74 Health Centers (HCs) in Tohoku District. The response rate was 100%. The Service Report of Activities of HCs (1992) was also utilized as the basic data for estimating statistical indices concerning contact examination. Results obtained are as follows: 1. At a rough estimate, the number of persons who underwent the contact examination accounted for 1.6 per newly diagnosed cases with tuberculosis in Japan. This index remarkably varied according to the region, e.g., maximum was 6.6 in Okinawa and minimum was 0.9 in Yamaguchi. The contacts had a high incidence rate (0.65%) with active tuberculosis. This rate was twenty five times higher than that by periodic mass X-ray examinations. 2. In Tohoku District, only 17 HCs (23%) carried out the examination fitting "guidelines" that had been published by the Ministry of Health and Welfare. Results from the program assessment suggested that HCs should give priority of the examination to the contacts because they were risky. The risk of manifestation is mainly influenced by bacteriological severity of source cases. 3. Main planners of the examination were public health nurses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7884993 TI - [The control of tuberculosis patients: the current situation and perspective in Japan]. AB - In Japan, Incidence and Death rate of tuberculosis were decreased marvelously after World War II, because of complete TB control system. But, the system are constructed to be adapted to high incidence, so it should be improved to be suitable for present situation. In Tokyo, average period of TB therapy are 10.2 month, and default rate is only 2.8%. But, default cases have severe social risk factors. Besides, this statistics cannot be collected with present TB surveillance system. Then there are some problems to improve the system. 1. How to cope with high risk patient. 2. How to evaluate the effect of TB control. 3. How to cope with default case. 4. How to consist comprehensive community TB control system. To solve these problems, 5 measures are suggested. 1. Establish systems to evaluate the quality of TB control. 2. Improvement of the technology to support patients from a viewpoint of health promotion. 3. Strengthening cooperation between hospitals and health centers. 4. Integration TB control to comprehensive community health care system. As same as TB control system made the basis of health care system in Japan, improvement of TB control system will be contribute to the progress of public health system in Japan. PMID- 7884994 TI - [The present status and future roles of tuberculosis advisory committees]. AB - We surveyed the present status and future roles of Tuberculosis (TB) Advisory Committees to study the ideal concept of the Committees using questionnaires. After the introduction of the new TB Control Law (which allowed the integration of the Committees), about half of the local governments (prefectures, special cities and special wards in Tokyo) have decreased their committees numbers by a third to two-thirds of the original number of health centers. In order to improve the quality of the Committees, there were additional educational activities suggested by the respondents in the questionnaire. However there were several problems highlighted in the questionnaire, for example a decrease in TB specialists, the aging of Committee members and some Committees with extremely low numbers in reported cases of TB. For the improvement of the Committees both in quality and the range in activities, it is not enough to integrate the Committees. It is recommended that the Committees should be improved in training and education for doctors and staff of the health centers and that they contribute more in comprehensive counter measures against TB in each region. In future the Committees roles should be enlarged and improved in quality, for example, to carry out extra periodic mass screening for TB, and to examine the chest x-rays in mass screenings for lung cancer. PMID- 7884995 TI - [Usefulness of percutaneous instillation of antifungal agents for pulmonary aspergilloma]. AB - We studied the usefulness of percutaneous instillation of antifungal agents for treatment of pulmonary aspergilloma. The subjects were six patients, four males and two females, with a mean age of 69 years (range, 45 to 90 years). In all cases, radiography revealed a fungus ball or thickened cavity wall in residual tuberculous cavities. The patients had clinical symptoms including hemoptysis, fever, cough and sputum, and most of them showed severe emaciation, anemia, hypoalbuminemia and hypoxia. Miconazole or fluconazole was instilled through an indwelling catheter inserted percutaneously into the cavity from the anterior chest wall or parascapular region under fluoroscopic observation. After treatment with a total dose of 610 to 2070 mg over a period of 6 to 18 weeks, clinical symptoms were diminished in all patients and radiographic findings were improved in five. Furthermore, Aspergillus fumigatus, which had been isolated from sputum samples of three patients, was eradicated. According to evaluation of the overall therapeutic effects, this therapy was considered to be effective in five patients, giving an efficacy rate of 83%. No recurrence has been detected in six patients during a mean follow-up of 13 months after treatment. Since percutaneous instillation involves less pain and stress than other kinds of PMID- 7884996 TI - [Histopathological, electron microscopic and microbiological studies in patients with obstructive large-bowel ileus of tumor origin]. AB - We have studied the Liver and colon of 23 patients histologically, and 15 electron microscopically. In the course of light microscopic observation of the colon wall above the obstruction we found: degeneration and desquamation of epithelial lining, decrease of goblet cells, increase of acid glycoproteins, hypertrophy of myofibrils in the muscle layer and fibrogenesis in the interstitial tissue in between. In liver: there was slight to moderate fibrosis in portal tracts and somewhere in the sinusoids, and moderate inflammatory infiltrate in them. Electron microscopic observations showed: a. in colon above the carcinomatous obstruction we found hypertrophy of muscle cells and in between collagenoblasts I-II type; b. in liver without metastases the space of Disse was distended, with bundles of collagen somewhere. Ito cells showed signs of fibroblast transformation. Our hypothesis is that these chronic changes are a reaction to the protracted obstruction and to colon carcinoma. PMID- 7884997 TI - [The surgical treatment of hyperthyroid goiters--the current approach and the trends]. AB - Proceeding from the analysis of 848 patients with hyperthyroid goiter, including all three nosological entities--Graves' disease (538), toxic adenoma of the thyroid (126), and struma basedowificata nodosa (184)--operated in the clinic of endocrine surgery over a five-year period, some modern trends in the therapeutic approach are discussed, preoperative preparation of the patients and resection scope, in particular. It is recommended to discard preparation with the classical Lugol's solution in mild and medium severe forms of Graves' disease, routinely used in the clinic over the past few years, and operate after administration of 1 2 tablets Metizole which shortens preoperative hospitalization, and secures postoperative period free of hyperthyroid complications. PMID- 7884998 TI - [The gastric location of an ectopic pancreas]. AB - Over the past six years, three patients presenting ectopic pancreas with a gastric location are subjected to treatment in the surgical clinic. In all three cases the ectopic glandular tissue is located submucously within the antrum. The clinical picture is diverse and not characteristic. Bleeding from the digestive tract is noted as a complication. The incidence, pathogenesis, pathoanatomy, clinical course, diagnosis and treatment of this relatively rare condition are discussed against the background of a comprehensive literature survey. PMID- 7884999 TI - [Morphine and benzodiazepine derivatives in cerebral angiographies]. AB - This is a report on thirty-two patients undergoing cerebral angiography, performed under combined local analgesia in conjunction with morphine and benzodiazepine derivatives. Emphasis is laid on the lack of serious life endangering complications. The risks of general anesthesia are avoided, and the patient's psyche is conserved. Investigations are performed during both planned and emergency angiographies. A pregnant female patient is also examined by the method described. There are no complications worth noting. The method is proposed as a procedure intermediate between general anesthesia and local analgesia. PMID- 7885000 TI - [An anatomicophysiological validation of hernioplasty in inguinal hernias]. AB - Contemporary understanding of the pathogenesis of inguinal hernias modifies the approach to solution of the problem from elementary anatomical to anatomical and functional. This in turn implies a number of specific demands on their treatment, such as: 1) preserving the oblique course of the canal in the abdominal wall, 2) endeavours to utilize the functionally synergetic elements of the respective layer for plastic repair of the defect, and 3) attempt at noninterference with the pump-valve function of the canal during plastic modelling of either of the openings. In both types of inguinal hernia, posterior plasties are pathogenetically justified. Positive experience had with 37 patients, operated for inguinal hernia after the methods of Shouldice, McVay and Kukudzhanov, or by combining single elements of the latter, is shared. The series analyzed comprises 18 cases presenting indirect hernia, 8-direct, 8-simultaneously direct and indirect, and 3-recurrent hernia. The extrafascial access to Cooper's ligament described contributes to the beneficial outcome. PMID- 7885001 TI - [Problems in the treatment of obstructive large-bowel ileus due to tumor origin]. AB - It is the purpose of the paper to present a comprehensive literature survey on the updated therapeutic approach to carcinoma of the colon, complicated by obturation ileus. In the past twenty years, colorectal carcinoma ranks first among malignant neoplasms, involving the gastrointestinal tract. During the period reviewed, the morbidity rate shows a nearly 4-to 5-fold increase. A rising incidence of the complicated forms of carcinoma of the colon-with obturation ileus the commonest of them-is likewise recorded. Regarding the treatment of this complication there is no agreement among surgeons in terms of the surgical tactics to be adopted and the scope of operative intervention. There is a great number of diverse problems, still not well enough clarified, relating to performance of one-or two-staged operation, removal of the tumor in the first stage and the like. The views on whether or not the operation should terminate with intestinal passage restoration in the first stage, especially in case of carcinoma located in the left half of the colon, are conflicting. PMID- 7885002 TI - [The diagnosis and surgical possibilities in rectal carcinoma]. AB - This is a review article dealing with the role and indications of the various diagnostic methods and operative techniques, used in the surgical management of rectal carcinoma. Preoperative assessment of the clinical stage of neoplasm has an essential practical bearing on the choice of operative procedure the most adequate for individual patients. In practice the factors influencing the decision for surgery include: summed up evaluation of all initial data, critical assessment of local findings, judgement based on past experience, a propensity to accept risks, and capability of undertaking determined actions. The first two parameters appear to be the most important, influencing in turn the subsequent stages on which the outcome of surgical intervention is largely dependent. PMID- 7885003 TI - [Peritoneal carcinosis diagnosed during herniotomy]. AB - A case of inguinal hernia is described where metastasis from adenocarcinoma with mucinous products in the bottom of the sac are discovered intraoperatively. Prior to operation, the patient is suspected for abdominal organ carcinoma, but no evidence of such a lesion is documented. Persistent complaints of painfulness in the region of hernia is the cause prompting the undertaking of herniotomy. Whenever the hernial sac is implicated in pathologic processes involving peritoneum and abdominal organs, the clinical manifestations of the intraabdominal process and of the hernia proper are modified. PMID- 7885004 TI - [Wilms' tumor--a rarely encountered disease in adults]. PMID- 7885005 TI - [A case of xanthogranulomatous pyelonephritis]. PMID- 7885006 TI - [A case of an adrenal gland tumor (dysgerminoma) metastasized to the neck area]. PMID- 7885007 TI - [Recurrent nasal polyposis]. PMID- 7885008 TI - [Peritonitis of large-bowel origin--complicated colorectal carcinoma]. AB - A total of 803 patients presenting colorectal carcinoma are operated on over a 14 year period (1979 through 1992). In 272 cases (33.8 per cent) the disease runs a complicated clinical course. Perforative peritonitis is recorded in 29 cases-10.6 per cent of the total number of patients with complicated course, and 3.6 per cent of the total number subjected to operation. Ileus peritonitis free of perforation is discovered in twenty-seven cases-9.5 per cent of 272, and 3.23 per cent of the total number-803. The microbiological study of abdominal cavity exudate from the patients with ileus peritonitis points to predomination of anaerobic micro-organisms, having an essential practical bearing on performing adequate perioperative and postoperative antibiotic treatment, and peritoneal cavity lavage during the operation. Radical two-staged operations with removal of the perforated neoplastic process in the first stage and preternatural anus formation are the method of choice. Palliative operations leaving the perforated carcinoma within the abdominal cavity account for 100 per cent lethality. A radical one-staged operation is indicated only in the event of localized peritonitis, young patients, preserved good general condition, usually following right hemicolectomy. PMID- 7885009 TI - [Anemia in acute kidney failure following peritonitis--its causes, development and treatment]. AB - Twelve patients presenting postoperative acute renal failure (ARF), developing after peritonitis, are subjected to follow-up study. A comparative assessment of the renal function and anemic syndrome is done during three different periods: immediately after the operative intervention, after renal failure development, and at treatment completed. For the purpose a number of indicators are monitored, namely: hemoglobin, hematocrit, erythrocytes, blood platelets, urea, creatinine, serum calcium and iron levels, diuresis and creatinine clearance (Ccr). Two patients are given human recombinant erythropoietin (rHuEpo). As demonstrated by the results, erythropoietin (Epo) deficiency is the underlying cause of concurrent anemia occurring in postoperative ARF; the anemia syndrome develops parallel to renal failure development. In patients given rHuEpo the anemia lends itself readily to control, renal failure subsides completely within shorter periods of time, and the incidence of hemorrhagic accidents is reduced. PMID- 7885010 TI - [Recurrent subacute endocarditis caused by Streptococcus mutans in a child]. AB - Bacterial endocarditis belongs to the rare diseases in childhood. It occurs usually as a single episode and almost exclusively in children with congenital heart disease. In recent years, however, an increased number of renewed endocarditis after the first episode were reported, especially in drug addicts. We present a case of renewed subacute infective endocarditis 3 years and 9 months after complete recovery from the first one. Furthermore, using the available literatures, the role of risk factors, the change in spectrum of the infecting organisms, the diagnostic and therapeutic approach in cases with renewed infection are discussed. PMID- 7885011 TI - [Hearing disorders in children less than 16 months of age after bacterial meningitis with reference to cerebrospinal fluid elastase]. AB - Hearing impairment as a sequela of acute bacterial meningitis is a well known complication. Dexamethasone therapy in addition to antibiotics is beneficial in the reduction of deafness, implicating that inflammation may be one reason for hearing impairment. The risk of hearing impairment in different types of bacterial meningitis is well studied. In very young children < 1.5 years of life the incidence of hearing loss and the possible correlation of laboratory data with the development of deafness is yet unknown. We therefore examined the brainstem auditory evoked potentials in 25 children between the first month and the 16th month of life who we treated for meningitis during 3 years in our hospital. 11 children were treated with dexamethasone. In 9 children we found abnormal brainstem auditory evoked potentials, which we controlled every 3 months. 7 children had transient conductive hearing impairment with good recovery during the first year after the disease. In 2 cases we found permanent bilateral sensorineural hearing loss. There was a significant relationship between hearing loss and elastase in cerebrospinal fluid. Dexamethasone reduced this relationship. A screening of hearing should be performed as routine control in all patients with acute meningitis. The association of high elastase in cerebrospinal fluid and later hearing impairment indicates a pathophysiological relation between activation of granulocytes and hearing loss. PMID- 7885012 TI - [Autosomal dominant cerebral seizures in the 6th month of life with benign outcome]. AB - We report a boy with benign familial seizures of the sixth month of life. At the age of six months he suffered his first afebrile grand mal seizure. Up to his ninth month several seizures of the same type occurred. EEGs were always normal. The history yielded a paternal hereditary trait: five members of the family had also suffered grand mal seizures in the sixth month of life. All but one had no therapy with antiepileptic drugs. One girl was treated with phenobarbital for two years. All members of the family show normal neurological development. Under low dose therapy with phenobarbital our patient has remained seizure-free up to now. PMID- 7885013 TI - [Neurological complications in infectious endocarditis]. AB - Despite considerable progress in both diagnostic studies and therapeutic management serious complications of infectious endocarditis have become rather more common. Next to intracardiac complications arterial embolization to the central nervous system is the second most common life-threatening event, which might lead to infarction, hemorrhage, mycotic aneurysm and/or metastatic infection with a wide spectrum of neurological symptoms and an overall very poor prognosis. The most effective prevention of neurological complications is the early diagnosis of infectious endocarditis with isolation of the infecting agent and adequate antimicrobial chemotherapy in combination with well-timed cardiosurgical measures. Computed tomography and cerebral angiography is mandatory in any patient with neurological symptoms to check the need for a neurosurgical intervention as well as in patients assigned for anticoagulation for cardiac reasons. PMID- 7885014 TI - [Hereditary motor and sensory neuropathy type III. Case report and review of the literature]. AB - We report on a 6 years old girl, who was first presented at the age of 3 1/2 years with progressive ataxia, coordination disturbance and distal motoric weakness (especially hand-weakness). Diagnostic procedure revealed heredomotorsensoric neuropathy type III (syn. Dejerine-Sottas Disease). PMID- 7885015 TI - [Necrotizing enterocolitis: a 12-year retrospective study]. AB - Necrotizing enterocolitis (NEC) is the most relevant intestinal acquired complication during the neonatal period. Due to the improvements in perinatal medicine during the last decade, we wanted to work out possible differences in the incidence, diagnosis and clinical courses of NEC during a 12 years period. PATIENTS AND METHODS: All premature or term newborns were eligible for the study, if a necrotizing enterocolitis > or = stage 2a according to Bell was diagnosed between January 1980-December 1991. RESULTS: During the study period, 90 preterm or term newborns were treated for necrotizing enterocolitis, 19 infants were admitted to our hospital for therapy of established NEC from other hospitals. Forty-five infants had a birthweight of < or = 1500 g. During the years 1987-1991 there was an increase in the incidence (4-12/year, median 9/year, compared to 0 6, median 3/year during the period 1980-1986). This was paralleled by an increase in very low birthweight infants admitted to the NICU (1980-1986: 35-45/year, 1987 1991: 83-108/year). Prominent clinical signs: abdominal distension (85 infants), increased gastric residuals (72), bright blood from rectum (56). Median time of manifestation in infants < or = 30 weeks was 17 days, for infants of 31-34 weeks 8 days and for infants of > or = 35 weeks of gestation 4 days. Eleven infants were fed parenterally exclusively before NEC, 12 infants received exclusively breast milk, 67 formula. Surgical treatment was indicated in 51 infants (indication: intestinal perforation or peritonitis diagnosed by abdominal paracentesis). Seventy-one infants survived, in 17 infants who died, NEC or secondary disorders were the main cause. CONCLUSION: With increasing numbers of very preterm infants, the relevance of NEC becomes more and more important. Concepts of prevention and early diagnosis further have to be worked out. PMID- 7885016 TI - [Case report of congenital afibrinogenemia]. AB - It is reported about a case of congenital afirinogenaemia on a newborn female. The treatment is described. Congenital afirinogenaemia is a rare autosomal recessive disorder. There are 250 cases in world literature, mostly with consanguineous parents. Bleeding is usually mild, so that treatment should not be prophylactic, because any blood product might cause complication, like AIDS. Only acute haemorrhage should be treated with fresh frozen plasma or fibrinogen concentrates. PMID- 7885017 TI - [Recommendations for prevention and therapy of malaria. German Society of Pediatric Infectiology e.V. (DGPI), "Parasitology" Study Group]. PMID- 7885018 TI - [Recommendations for the treatment of prenatal toxoplasma infection in the child. German Society of Pediatric Infectiology e.V. (DGPI), "Parasitology" Study Group]. PMID- 7885019 TI - [The physiologic significance of Bifidobacteria and fecal lysozyme in the breast fed infant. A contribution on the the microecology of the intestine]. AB - The fecal microflora of the breast-fed infant consists of nearly 100% Bifidobacteria. The importance of this long-known and unique phenomenon is still not clearly understood. Likewise, the presence of lysozyme in the feces of breast fed infants, which is administered in significant amounts with the human milk is not adequately known. New hints and hypotheses concerning digestion in ruminants are cited. In ruminants Lysozyme c functions as digestive enzyme in the rumen. Lysozyme causes lysis of the bacterial cell membrane leading to the release of bacterial contents i.e. proteins. The proteins synthesised in bacteria are the main source of nitrogen for ruminants. The hypothesis is established, that the enormous amounts of Bifidobacteria in the colon of the human newborn can be made of use in a similar way. The lysozyme in the colon of breast-fed infants leads to lysis of Bifidobacteria in connection with tryptic digestive enzymes, in turn leading to release of proteins and protein substances. It has recently been demonstrated that catabolic products of these proteins can be absorbed in the colon. The same group has shown that lysis of Bifidobacteria can take place in the presence of lysozyme in connection with trypsin. PMID- 7885020 TI - [Predictive value of latex agglutination on Helicobacter pylori in children with recurrent abdominal pain]. AB - In a prospective investigation, a rapid latex test for Helicobacter pylori in the serum (Pyloriset) was carried out in 39 patients with recurrent abdominal pain aged from six to 15 years. The test was positive in 19 patients. All of these children were subjected to gastroduodenoscopy. Seven cases showed a Helicobacter associated chronic active antrum gastritis, whereas in the remaining 12 children gastritis not induced by Helicobacter or normal mucosa was found. Of the 20 Pyloriset-negative patients, only five could be biopsied. One of these showed a Helicobacter pylori-induced antrum gastritis. The latex test investigated had a positive predictive value which was too low (37%) to make it helpful in deciding for or against gastroduodenoscopy and the general anesthesia mostly associated with this. PMID- 7885021 TI - Effects of lipids on intestinal adaptation following 60% resection in rats. AB - The effects of long-chain triglycerides (LCT) and of medium-chain triglycerides (MCT) on intestinal adaptation in rats were compared following a 60% resection of intestine. Sixty Long-Evans rats were divided into four groups: control (sham operated) rats fed an MCT-enriched diet, control rats fed an LCT-enriched diet, experimental rats fed an MCT-enriched diet, and experimental rats fed an LCT enriched diet. In the MCT-enriched diet, 90% of the fat was MCT; in the LCT diet, 90% was LCT. In each diet, 31-32% of daily caloric intake came from fat. All diets were isocaloric and isonitrogenous. Following the 60% intestinal resection from the mid-portion of the small intestine, there were significant increases in mucosal height, villous height, villous width, and crypt depth (P < 0.05). Gut weight, mucosal weight, protein and DNA content, and DNA synthetic rate also increased. In the ileum, rats receiving the LCT diet showed greater increases in gut weight, mucosal weight, crypt depth, protein and DNA content, and DNA synthetic rate than the MCT rats did (P < 0.05). In the jejunum, however, the differences were not statistically significant. In both the jejunum and the ileum, the response of the intestine was greater closer to the anastomotic site (P < 0.05). Results of these studies demonstrated that LCT had a better effect than MCT on intestinal response both structurally and functionally. PMID- 7885022 TI - The effect of insulin-like growth factor-1 on protein metabolism and hepatic response to endotoxemia in parenterally fed rats. AB - To determine the influence of insulin-like growth factor-1 (IGF-1) on nitrogen loss and hepatic response to critical illness, 34 male Sprague-Dawley rats (190 230 g) were randomized to receive parenteral nutrition (PN) only (Ctrl), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), or PN plus LPS plus rhIGF-1 (IGF-1) at 3 mg/kg/day for 48 hr. Prior to randomization, all animals underwent iv cannulation and 30 hr of adaptation to PN. All animals received isocaloric and isonitrogenous PN (glucose 170 kcal/kg/day and nitrogen 1.1 g/kg/day) and were kept NPO except for water ad libitum. [15N]glycine was infused in all animals for determination of liver fractional synthetic rate. Cumulative nitrogen balance during endotoxemia was significantly different from each other (+72 +/- 42, -217 +/- 131, -114 +/- 137 mg/kg/48 hr for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.001). Endotoxin significantly increased the urinary 3-methylhistidine/creatinine ratio (0.24 +/- 0.05, 0.55 +/- 0.12, 0.48 +/- 0.17 for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.001); however, IGF-1 did not significantly reduce the ratio. Endotoxin induced a significant increase in liver fractional synthetic rate (29 +/- 8, 56 +/- 18, 64 +/- 12%/day for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.01) and depressed hepatic cytochrome P450 concentration (0.54 +/- 0.19, 0.22 +/- 0.07, 0.19 +/- 0.07 nmol/mg protein, respectively; ANOVA, P < 0.05) and ethoxycoumarin O-deethylase (ECOD) activity (103 +/- 73, 29 +/- 13, 17 +/- 11, pmol/mg/min, respectively; ANOVA, P < 0.01); however, rhIGF-1 did not significantly alter these hepatic variables during endotoxin infusion. Recombinant human insulin-like growth factor-1 significantly improved nitrogen balance without compromising hepatic response as measured by liver fractional synthetic rate, cytochrome P450 concentration, and ECOD activity in endotoxemic parenterally fed rats. PMID- 7885023 TI - Expression of cytokine genes during liver regeneration after partial hepatectomy in rats. AB - In the present study to demonstrate the relationship between cytokines and liver regeneration we investigated by Northern blot hybridization the cytokine gene induction in the regenerating liver and several other organs (spleen, lung, and kidney) in the rat after partial hepatectomy (PH). We also examined whether Kupffer cells and the spleen are involved in the induction of cytokine mRNA in the regenerating liver. Both IL-1 alpha and beta mRNA increased transiently 1/2 to 1 hr after PH in nonparenchymal cells (NPC) of the regenerating liver; they reached a maximum before the peak of hepatocyte DNA synthesis. PH also induced a slight, but significant, gene expression of IL-1 in lung and kidney in the early postoperative period. TNF-alpha mRNA increased gradually in the spleen, but not the liver, of partially hepatectomized rats at 3 to 12 hr and then reached a peak at 24 hr after PH. IL-6 transcripts were not detected in the regenerating liver, spleen, lung, or kidney during liver regeneration. In contrast, no cytokine gene expression was induced in any of these four organs during the first 3 days after sham operation or unilateral nephrectomy. When Kupffer cell activity was suppressed by gadolinium chloride pretreatment, or when splenectomy was performed 24 hr before PH, the constitutive IL-1 alpha and beta mRNA expressions in NPC of the normal rat liver were completely suppressed. In conclusion, the present study demonstrates, for the first time, the specific kinetics of cytokine gene expression in the liver, spleen, lung, and kidney after PH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885024 TI - Influence of surgical stress on monocytes and complications of infection in patients with esophageal cancer--monocyte HLA-DR antigen expression and respiratory burst capacity. AB - We investigated how surgical stress affects the phenotypic and functional properties of peripheral blood monocytes, especially the expression of human leukocyte antigen DR (HLA-DR), Mac-1 antigen, and respiratory burst capacity. Then, we analyzed the relation between these monocyte parameters and septic complications following esophagectomy. Increased H2O2 production (605.3 +/- 95.3 fluorescence intensity (FI) vs 441.8 +/- 55.5 FI) in the preoperative period and decreased HLA-DR expression (20.5 +/- 5.5% vs 39.6 +/- 11.1%) on monocytes on the 1st postoperative day (POD) were found in esophagectomy patients (n = 14) compared with gastrectomy patients (n = 29). Furthermore, the level of increased H2O2 production and decreased HLA-DR expression continued on the 8th and 14th POD in the esophagectomy group with septic complications compared with the esophagectomy group without septic complications. These results suggested that patients with septic complications following esophagectomy had alterations of monocyte phenotype and function. This monocyte analysis may contribute to our understanding of the complicated mechanism involved in surgical stress and the development of postoperative septic complications. PMID- 7885025 TI - Duration of liver ischemia and hepatic regeneration after hepatectomy in rats. AB - Since an occlusion of the vascular inflow to the liver is a useful technique in liver surgery, a relation between ischemia and regeneration in the liver is particularly important. The purpose of this study was to evaluate the effect of ischemic duration on liver regeneration after massive hepatectomy. Animals were subjected to segmental liver ischemia. After 30, 60, or 90 min, nonischemic liver lobes were resected (70% hepatectomy). Hepatectomy without prior liver ischemia was performed in the control group. On the 1st, 3rd, 5th, and 7th days following hepatectomy, a BrdU labeling index was calculated as a marker of liver regeneration. AST, ALT, and liver adeninenucleotides were also measured. Although 30 min of liver ischemia resulted in higher peak AST and ALT levels, liver regeneration and ATP levels were significantly higher than those in control animals. Ninety minutes of liver ischemia resulted in significantly lower liver regeneration and ATP levels compared with the other treatment paradigms. Liver regeneration and ATP levels were almost identical to those in control animals, in rats with 60 min of ischemia preceding hepatectomy. We conclude that livers regenerative capacities can tolerate significant ischemia and that relatively brief periods of ischemia can even accelerate liver regeneration. PMID- 7885026 TI - Dose-response study of the effect of growth hormone on mechanical properties of skin graft wounds. AB - The aim of the study was to investigate the effect of growth hormone on compromised wound healing in a model without exogenously applied metabolic disturbances, e.g., diabetes mellitus. Female Wistar rats were injected with biosynthetic human growth hormone (b-hGH) at 2.0, 4.0, 8.0, and 16.0 mg/kg/day from 7 days before operation to 7 days after. Controls were given saline. On the left side of the dorsal skin a 35 x 20-mm full-thickness skin graft was raised and replaced in situ. After 7 days of healing the wound between the graft and the skin was tested mechanically. The maximum load and maximum stiffness showed a positive correlation with dose of b-hGH, being increased by 40 and 47% in the 8.0 mg group and 34 and 48% in the 16.0 mg group compared with the saline group. During the 7 days of injection before operation serum insulin-like growth factor I (IGF-I) decreased in the saline group, was unchanged in the group given 2.0 and 4.0 mg b-hGH, and was increased in the groups given 8.0 and 16.0 mg b-hGH. Postoperatively, no changes in se-IGF-I were seen in any of the groups when compared to the values at operation. Blood glucose was unaffected by b-hGH treatment. Postoperatively the saline-treated rats showed an 8% weight loss and the 2.0 mg b-hGH group a 3% weight loss, whereas no significant changes were seen postoperatively in the 4.0, 8.0, and 16.0 mg b-hGH groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885027 TI - Endothelium-dependent relaxation in response to adenosine diphosphate is impaired under poor runoff conditions in the canine femoral artery. AB - To examine whether poor distal runoff conditions of the canine femoral artery modulates endothelium-dependent relaxations, we developed a poor distal runoff limb in the canine right femoral artery (poor runoff group). The left femoral artery was used as a control. Endothelium-dependent responses were examined in vitro. The rings of femoral artery were obtained from dogs pretreated with 6 weeks of poor distal runoff. In the control, flow rate and tau-variation were 79.1 ml/min and 214.2 dynes/cm2, respectively. In the poor runoff group, the flow rate and tau-variation were 27.4 ml/min and 52.7 dynes/cm2. There were significant differences between the two groups. In the rings taken from the control group contracted with norepinephrine, adenosine diphosphate (ADP) and A23187 caused endothelium-dependent relaxations. In the poor runoff group, the endothelium-dependent relaxations in response to ADP were impaired, while A23187 caused comparable endothelium-dependent relaxations. Direct relaxations in response to sodium nitroprusside were comparable between the two groups. These experiments indicate that under poor runoff conditions, the endothelium-dependent relaxations to ADP are impaired without changing the properties of the smooth muscle cells. This dysfunction of the endothelium under conditions of abnormal flow may accelerate a loss of late patency of the reconstructed arteries. PMID- 7885028 TI - Enhancement of peritoneal macrophages reduces postoperative peritoneal adhesion formation. AB - Postoperative adhesion formation results from a fibroproliferative inflammatory reaction. Macrophages are critical in the final resolution of the inflammatory process and tissue repair, including modulation of proliferation and differentiation of fibroblasts and secretion of neutral proteases like plasminogen activator. We, therefore, studied the influence of peritoneal macrophage enhancement on postoperative adhesion formation in five groups of rabbits. Group 1 was a control with normal peritoneum. Animals in group 2 had increased macrophage population in their peritoneum by intraperitoneal injection of protease peptone 3 days before adhesion induction. In group 3, animals were treated by protease peptone as in group 2 and then depleted of the increased macrophage population by peritoneal lavage before adhesion induction. In group 4 macrophages were transplanted from animals enriched as in group 2 into a nonenriched peritoneum at the time of adhesion induction. Group 5 had a normal peritoneum with peritoneal lavage before adhesion induction. Peritoneal adhesions were induced at laparotomy by repairing a peritoneal defect in two different models. It was found that enhancement of peritoneal macrophages by protease peptone reduced markedly the degree of postoperative adhesion formation. After depletion of the enhanced peritoneal macrophages by peritoneal lavage the degree of adhesion formation was equivalent to that of controls. Finally, macrophage transplantation into a nonenhanced macrophage peritoneum also reduced the degree of postoperative adhesion formation. It is concluded that enhancement of peritoneal macrophages reduces postoperative peritoneal adhesion formation. PMID- 7885029 TI - In vitro evaluation of nicorandil, diltiazem, and prostaglandin E1 on hypothermic injury to immature myocytes. AB - The purpose of the present study was to evaluate the functional and biochemical effects of nicorandil (NRD), diltiazem (DTZ), or prostaglandin E1 (PGE) on cardiac myocytes incubated under hypothermic conditions. Cardiac myocytes were isolated from neonatal rat ventricles and cultured for 4 days with MCDB 107 medium. Myocytes (12.5 x 10(5) myocytes/flask) were then incubated at 4 degrees C for 24 hr in media containing various concentrations of NRD, DTZ, or PGE. After hypothermic incubation, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) were measured. The myocytes were then cultured for an additional 24 hr at 37 degrees C to evaluate the recovery of myocyte beating rate. In the nicorandil groups, 10(-4) M NRD showed significantly increased beating rate recovery compared to control (44.2% vs 24.6%, respectively, as a percentage of control, i.e., beating rate prior to hypothermic incubation). Treatment with 10(-6) M diltiazem showed no beneficial effects (10(-6) M: 25.2%; control: 29.8%); however, beating was not observed at 10(-4) or 10(-5) M. There were no significant changes among the PGE groups. The release of CPK and LDH was significantly suppressed with 10(-4) M NRD (10(-4) M: 24.1, 257.2 MIU/flask; control: 125.4, 459.5 mIU/flask, respectively). However, 10(-4) M DTZ showed significantly increased CPK and LDH levels compared to the control (10(-4) M: 203.3, 883.4 mIU/flask; control: 112.3, 457.4 mIU/flask, respectively). There were no significant differences for CPK and LDH levels among the PGE groups. In conclusion, nicorandil has protective characteristics for immature myocytes that may be suitable for cardiac preservation in the neonatal period. PMID- 7885030 TI - The enhancement in wound healing by transforming growth factor-beta 1 (TGF-beta 1) depends on the topical delivery system. AB - Transforming growth factor-beta 1 (TGF-beta 1) has beneficial effects on wound healing. However, the ideal method for its administration to the wound site remains unknown. Our aim was to analyze the release of TGF-beta 1 from different formulations and to study whether the changes in wound healing by TGF-beta 1 depend on its topical delivery system. For the studies the TGF-beta 1 was incorporated into phosphate-buffered saline, into a polyoxamer gel, into DuoDERM hydroactive paste, and into a poly(ethylene oxide) hydrogel. The release of 125I labeled TGF-beta 1 from carriers was measured in full-thickness wounds in rats and the healing of the wounds was analyzed by histology and wound area measurements. The TGF-beta 1 was released from all formulations at a different rate and in an active form as determined by growth inhibition assay. Wound size measurements and the analysis on the amount of cellular influx, fibroplasia, and granulation tissue showed that a single dose (1 microgram/wound) of locally administered TGF-beta 1 significantly (P < 0.01) enhanced the wound healing. This effect was most prominent with polyoxamer gel formulation, which provided the most sustained release of TGF-beta 1. Our finding that the enhancement in wound healing by TGF-beta 1 was significantly dependent on the carrier used for its topical delivery to the wound site is novel and shows the importance of using adequate delivery systems when growth factors are used to enhance wound repair. PMID- 7885031 TI - The relationship between carotid plaque composition, plaque morphology, and neurologic symptoms. AB - Variations in plaque composition could make carotid artery plaques prone to ulceration, subintimal hemorrhage, plaque progression, or embolization and, thus, increase the risk of ipsilateral ischemic neurologic events. Seventy-eight carotid endarterectomy specimens from 74 patients (38 symptomatic and 36 asymptomatic) were analyzed. Prior to analysis, 43 of the 78 plaques were divided into sections based on disease severity and examined by light microscopy for surface ulceration and subintimal hemorrhage. Extracted lipid, cholesterol, collagen, and calcium content were determined in all 78 plaques and compared to clinical presentation and/or morphologic observations. Plaques removed from symptomatic patients contained more extracted lipid and cholesterol than those from asymptomatic patients. In addition, compared to the remainder of the plaque, the most stenotic portion of the plaque contained more cholesterol, more calcium, and less collagen. Finally, irrespective of clinical presentation, plaque sections found to have surface ulceration and subintimal hemorrhage contained more cholesterol and less collagen than plaques without these changes. Lipid laden plaques with low levels of collagen are associated with plaque ulceration, subintimal hemorrhage, and ischemic neurologic symptoms. This suggests that plaque composition may be an important factor in the pathophysiology of carotid atherosclerosis. PMID- 7885032 TI - Improved viability of hepatic allografts from fasted donors is associated with decreased peripheral TNF activity. AB - Despite improvements in preservation solutions, hepatic allografts continue to be lost from primary nonfunction. Previous work by this group and others has established that donor fasting improves the viability of hepatic allografts. We have also established an association between viability of stored organs and serum TNF levels. The purpose of this study was to determine whether improved viability of hepatic allografts from fasted donors is associated with lower peripheral serum TNF levels. TNF was measured using a bioassay employing a WEHI cell line. Transplanted livers from fasted donors displayed gross deglycogenation had less bile flow postrevascularization and increased postoperative AST, but had significant improvement in viability and were associated with significantly less TNF recovered from the peripheral circulation. The association of improved viability and diminished serum TNF and previous work that links changes in postrevascularization TNF levels with changes in Kupffer cell activity suggest a possible cause for improved survival of recipients of fasted allografts. PMID- 7885033 TI - The role of calcitonin gene-related peptide and nitric oxide in gastric mucosal hyperemia and protection. AB - It has been suggested that capsaicin-induced hyperemia and mucosal protection occurs via calcitonin-gene-related peptide (CGRP) release from gastric afferent sensory neurons and nitric oxide (NO)-mediated vasodilation. The purpose of this study was to determine whether capsaicin and/or bile acid induced hyperemia is mediated by CGRP and/or NO. Male Sprague-Dawley rats (280-350 g) were anesthetized, and the glandular stomach (blood supply intact) was chambered between two plastic rings. Animals were divided into six groups. Normal saline (groups 1 and 4), the NO inhibitor N-nitro-L-arginine methyl ester (L-NAME; 3.75 mg/ml, groups 2 and 5), or the CGRP antagonist hCGRP8-37 (0.047 mg/ml, groups 3 and 6) was continuously infused intraarterially (ia) close to the stomach at a rate of 0.034 ml/min for 1 hr via a catheter inserted retrogradely into the splenic artery. Fifteen minutes after the onset of this infusion, the gastric mucosa was topically exposed to neutral saline solution for 15 min, followed by 160 microM capsaicin for 15 min. The mucosa was then injured by a 15-min exposure to either 5 mM acidified taurocholate (ATC, pH 1.2) in groups 1-3 or 10 mM ATC in groups 4-6. Gastric mucosal blood flow (ml/min/100 g) was continuously measured (laser doppler), and injury was assessed by measuring net transmucosal H+ flux, luminal accumulation of DNA, and histologic grading (0 = no injury to 3 = severe) by an independent observer. Intraarterial infusion of L-NAME significantly blocked the hyperemic response of topical capsaicin while having minimal effect on bile acid-induced hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885034 TI - Autografting in chronic myelogenous leukemia: new questions. AB - In the 1970s, when autografting was started, it was hard to imagine that this procedure would have an application in hematological malignancies. Autografting in patients with CML has been difficult to pursue because their bone marrow is often contaminated by Philadelphia-chromosome positive cells. In recent years, renewed interest has come from this procedure and various in vivo or in vitro techniques of manipulation of Ph-positive cells, such as collection of blood progenitor cells in the early phase of recovery after intensive conventional chemotherapy in untreated or pretreated patients, long-term bone marrow culture and chemical purging of marrow cells. Despite all these interesting trials, we do not have enough data to address the question of whether autografting in CML increases the duration of the chronic phase. PMID- 7885035 TI - Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoiesis and a high incidence of P53 mutations. AB - We looked for correlations between cytogenetic rearrangements leading to 17p deletion and presence of dysgranulopoiesis and p53 mutations in MDS and AML. Forty-nine (4.3%) of the MDS and AML studied cytogenetically at our institution over a period of 11 years had detectable 17p deletion, through monosomy 17 (14 cases) or rearrangements of chromosome 17 (generally unbalanced translocations between 17p and another chromosome) (35 cases). Most of the patients had additional complex cytogenetic findings, and 10 cases were therapy related. In 70% of the patients with 17p deletion, a particular type of dysgranulopoiesis, combining pseudo-Pelger-Huet anomaly and small vacuolated neutrophils was seen in > 5% marrow neutrophils, whereas 69% of the patients had a p53 mutation, generally in a missense mutation involving exons 5 to 8 of the p53 gene. FISH analysis, performed in eight cases, confirmed loss of one P53 allele in all of them. No DNA fragmentation suggesting increased apoptosis was found in marrow samples. Response to chemotherapy was almost uniformly poor and median survival was only 3 months. Analysis of dysgranulopoiesis and p53 mutations were also made in 'control' groups of MDS and AML without 17p deletion. 'Typical' dysgranulopoiesis, combining pseudo-Pelger-Huet anomaly and small vacuolated neutrophils in > 5% marrow neutrophils, was not seen in any of the 47 MDS and AML without 17p deletion analyzed and without p53 mutation (P = 10(-4) with patients having 17p deletion), and was seen in one of five patients without 17p deletion but with a p53 mutation. Only 3.1% of 256 MDS and AML without 17p deletion had a p53 mutation (P = 10(-4) with patients having 17p deletion). These findings suggest that 17p deletion, in MDS and AML, is strongly correlated to the presence of a particular type of dysgranulopoiesis and to a high incidence of p53 mutations, and that MDS and AML with 17p deletion could constitute a new morphological-cytogenetic-molecular entity in myeloid disorders. PMID- 7885036 TI - Therapy with OKT3 monoclonal antibody in refractory T cell acute lymphoblastic leukemia induces interleukin-2 responsiveness. AB - Administration of cytokines to patients with leukemia or lymphoma may recruit dormant malignant cells into cell cycle and thus make them more susceptible to chemotherapy. We treated a patient with refractory T cell acute lymphoblastic leukemia (ALL) with OKT3 monoclonal antibody and observed a dramatic but transient decrease of lymphoblasts. The T ALL cells were rather mature by morphology and immunophenotyping, expressing CD7, CD4, CD8 and CD3 surface antigens and nuclear TdT. Cytogenetic analysis revealed inversion of chromosome 14(q11q32.1). A total of 500 mg OKT3 (maximum dose 50 mg/day) was given. A decrease of lymphoblasts in the blood and a reduction of spleen size was observed. Complement levels dropped remarkably. Despite increasing serum levels of tumor necrosis factor, treatment was well tolerated overall. CD3 therapy induced strong IL-2 responsiveness of the lymphoblasts. Thus, OKT3 antibody treatment not only significantly decreased CD3-positive tumor cells, but also induced IL-2-mediated proliferation. This may also allow sequential application of CD3 and IL-2 to render certain T cell tumors more susceptible to chemotherapy. PMID- 7885037 TI - Prognostic relevance of ALL-1 gene rearrangement in infant acute leukemias. AB - We and others have recently reported a high frequency (70-80%) of ALL-1 (MLL, HRX, HTRX) gene rearrangements in infants with acute leukemias (AL) aged less than 1 year. Preliminary observations in limited series also suggested that ALL-1 gene configuration is an important prognostic factor in this leukemic subset. We have now extended our study to a series of 45 AL patients aged between 0 and 18 months. The genomic configuration of ALL-1 in leukemic DNAs was determined by Southern blot hybridization and correlated with biological and clinical features at presentation, as well as with treatment outcome. Twenty-nine out of 45 (64%) patients showed ALL-1 rearrangements, including 4/11 (36%) infants aged between 13 and 18 months. Considering morphological types, 24/38 cases with acute lymphoblastic leukemia and 5/7 patients with acute myeloid leukemia showed ALL-1 rearrangements. The features more frequently found in association with ALL-1 rearrangements were hyperleukocytosis (P < 0.007) and CD19+/CD10- blast immunophenotype (P < 0.02). ALL-1 status was an independent prognostic marker of event-free survival (EFS) in a multivariate model including age, sex and WBC count, and maintained its statistical significance when FAB morphology was considered in the analysis by including AML patients. Considering the ALL cases the actuarial EFS was 57 and 9% for infants with germline and rearranged ALL-1 configuration, respectively (P = 0.008). A high frequency of ALL-1 gene alterations in infant AL is confirmed by this study. In addition, our results emphasize the need for extending the analysis of ALL-1 gene status to infants with AL aged > 12 months. We show that this genetic lesion is the most important variable negatively affecting prognosis in a multivariate model including other known risk factors. This latter observation should influence the choice of risk adapted treatment strategies in this AL subset. PMID- 7885038 TI - GM-CSF and asparaginase potentiate ara-C cytotoxicity in HL-60 cells. AB - In preparation for a clinical trial using GM-CSF on days 4-10 of sequential high dose cytarabine (ara-C) and asparaginase (ASNase) on days 1-3 and 8-10, potential interactions between the protein synthesis inhibitor ASNase and GM-CSF were evaluated. Granulocyte-macrophage colony-stimulating factor (GM-CSF) can stimulate acute myeloid leukemia (AML) cells to proliferate in vitro and in vivo. Log phase HL-60 cells were exposed to ara-C (10 microM x 3 h) and/or ASNase (10 U/ml during the last 2 h of ara-C). Ara-C and/or ASNase was removed and cells were incubated with or without GM-CSF (10 ng/ml). After 24, 48 and 72 h of GM-CSF there was no significant difference in the S phase fraction of cells exposed to ASNase prior to GM-CSF. Soft agar cloning efficiency was determined after retreatment with ara-C +/- ASNase 24 h into the GM-CSF incubation. GM-CSF enhanced cytotoxicity for all combinations, although this effect was of borderline significance (P = 0.0621); addition of ASNase to the treatment regimen significantly (P = 0.0229) enhanced cytotoxicity without any evidence of a negative interaction with GM-CSF. In addition, ara-C metabolism was assessed during simultaneous exposure to ara-C (10 microM x 3 h) +/- ASNase (10 U/ml the last 2 h) +/- GM-CSF (10 ng/ml beginning 24 h prior to ara-C). Ara-C incorporated into DNA (P = 0.0302) and ara-CTP formation (P = 0.0084 and P = 0.0003 at 2 and 3 h timepoints, respectively) were both increased significantly by GM-CSF, with modest non-significant increases with ASNase exposures. Neither ASNase nor GM-CSF inhibited the effects of the other in this in vitro model. Therefore, when appropriately scheduled, both GM-CSF and ASNase may potentiate ara-C cytotoxicity. PMID- 7885039 TI - Treatment of HL60 cells with various combinations of retinoids and 1 alpha,25 dihydroxyvitamin D3 results in differentiation towards neutrophils or monocytes or a failure to differentiate and apoptosis. AB - It is well documented that treatment of serum-grown HL60 cells with 10(-7) M all trans retinoic acid (all-trans RA) induces neutrophil differentiation, whereas treatment with 10(-7) M 1 alpha,25 dihydroxyvitamin D3(D3) induces differentiation towards monocytes. In recent investigations, using serum-free grown HL60 cells, we observed that all-trans RA, at 10(-7) M, did not induce neutrophil differentiation and that all-trans RA, at 10(-8) M, reduced the D3 concentration required for monocyte differentiation to 5 x 10(-9) M. In this study, co-operative interactions between all-trans and 9-cis RA and D3 which promote neutrophil and monocyte differentiation of HL60 cells have been analysed in detail. Treatment of serum-free grown HL60 cells with 5 x 10(-7) M all-trans RA or 9-cis RA resulted in sub-optimal neutrophil differentiation (up to 25% mature cells). As shown for all-trans RA, 9-cis RA cooperated with D3 to promote monocyte differentiation. Culture of HL60 cells in 5 x 10(-7) M 9-cis RA together with a wide range of concentrations of D3 resulted in promotion of neutrophil differentiation at 10(-15)-10(-12) D3, a failure to differentiate and apoptosis at 10(-11)-10(-10) M D3, followed by co-operativity between 9-cis RA and 5 x 10( 9) M D3 in inducing monocyte differentiation in the absence of neutrophil differentiation. Similar results were obtained when HL60 cells were treated with 5 x 10(-7) all-trans RA together with a wide range of concentrations of D3. Cross titration analyses of the effects of 9-cis RA and D3 on HL60 cell differentiation were undertaken to determine the boundaries of the concentrations of each agent, alone and in combination, that give rise to optimal neutrophil and monocyte differentiation of HL60 cells. The observed cooperativities between either 9-cis RA or all-trans RA and D3 have important implications for the use of combinations of these agents in differentiation therapy. PMID- 7885040 TI - IL-2 inhibits proliferation of K562 cells and reduces accumulation of bcr/abl mRNA and oncoprotein. AB - Cell lines of myeloid origin have been shown to express interleukin-2 receptors (IL-2R). Here, we demonstrate the expression of IL-2R alpha and IL-R beta on the CML blast cell line K562 by FACS analysis and cross-linking assay. Furthermore, we examined the effect of IL-2 on leukemic progenitor growth, employing K562 as a model. Clonogenic growth was assessed after 3 days of culture by colony formation in a serum-free, semi-solid assay system. IL-2 was found to exhibit a dose dependent suppressive effect on K562 clonogenicity with 48% inhibition of colony formation at 250 U IL-2 and 60% inhibition at 1000 U IL-2. Philadelphia chromosome (Ph)-positive K562 cells possess multiple copies of the bcr/abl fusion gene whose transcript and protein product (p210) is thought to confer growth advantage to CML cells. We therefore investigated IL-2-dependent modulation of bcr/abl mRNA accumulation and p210 protein levels in K562 cells. After 4 h of culture in the presence of IL-2, a 3-15-fold reduction of bcr/abl mRNA accumulation was demonstrated by competitive reverse PCR. Reduction of bcr/abl fusion protein levels was demonstrated at 24 h of IL-2-supplemented cell culture, employing p210 recognizing monoclonal antibodies (mAbs) in FACS analysis. Levels of proliferation marker Ki67 were only marginally affected. We conclude: (1) K562 cells express both IL-2R alpha and IL-R beta; (2) IL-2 inhibits clonogenic growth of K562 in a dose-dependent manner; and (3) IL-2-mediated inhibition of K562 proliferation is preceded by a reduction of bcr/abl mRNA accumulation and p210 protein levels. PMID- 7885041 TI - The spontaneous expression of interleukin-1 beta and interleukin-6 is associated with spontaneous expression of AP-1 and NF-kappa B transcription factor in acute myeloblastic leukemia cells. AB - The nature of the spontaneous expression of cytokines that is observed in blasts of some AML patients is unclear. We studied whether or not the spontaneous expression of IL-1 beta and IL-6 is due to an increased transcription rate of the cytokine gene and associated with a spontaneous expression of two transcription factors that play an important role in IL-1 beta and IL-6 gene transcription, namely activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B). In eight of the 19 AML patients a spontaneous expression of IL-1 beta mRNA was observed, whereas IL-6 mRNA was expressed in seven of the cases. Expression of IL 6 mRNA correlated nicely with the secretion of IL-6 protein. Nuclear run-on experiments showed that spontaneous expression of IL-1 beta and IL-6 was at least partly due to an increased transcription rate of the respective genes compared to the results from healthy unstimulated monocytes. Electrophoretic mobility shift assays demonstrated that especially spontaneous expression of NF-kappa B is associated with spontaneous cytokine expression. However, the spontaneous expression of transcription factors is not due to the endogenous secretion of IL 1 since the addition of anti-IL-1 monoclonal antibody did not affect the expression of NF-kappa B. Finally, supershift experiments were performed that demonstrated that the NF-kappa B consists of the p50 and the p65 subunits. In summary, these results demonstrate that the spontaneous expression of cytokines is frequently associated with an increased transcription rate and a spontaneous expression of transcription factors. PMID- 7885042 TI - Certain HLA antigens are associated with specific morphologic and cytogenetic subsets of acute myeloid leukemia. AB - Although many associations have been found between specific HLA antigens and an increased susceptibility to various diseases, previous attempts to associate class I and II antigens with acute myeloid leukemia (AML) have been inconclusive, probably due in part to the heterogeneity of AML. We subdivided 165 consecutive adults with AML de novo into distinct clinical, morphological, and cytogenetic subsets and then tested for statistically significant associations with specific HLA antigens. Both morphology and cytogenetic pattern identified subsets of patients with important clinical features and different outcomes. Ten statistically significant (P < 0.05) HLA cytogenetic associations were observed: HLA-A11 with t(8;21), A26 with t(15;17), B7 with 11q23 abnormalities, B44 with +8, Cw2 with -20/del(20q), DR3 with t(15;17) and FAB-M3, DR4 with inv(16) and FAB M4Eo, DQ2 with +8, and DQ6 with +22. HLA-DQ1 had a negative association with 5/del(5q), which was present in 13% of the 165 AML patients overall but in none of the 27 with DQ1. Certain HLA antigens were significantly correlated with more favorable remission rates, remission duration and survival. Possible mechanisms for the association of HLA antigens with particular subtypes of AML include the linkage or co-inheritance of an oncogene, the facilitation of binding of a transforming virus, toxin, or cytokine, or a permissive role involving impaired immune recognition of an emerging neoplasm. Given the heterogeneity of both the HLA system of immune recognition genes and the cytogenetic subtypes of AML, however, larger numbers of patients must be studied to have confidence that biologically important relationships truly exist. PMID- 7885043 TI - Preliminary evidence of an association between HLA-DPB1*0201 and childhood common acute lymphoblastic leukaemia supports an infectious aetiology. AB - It has been suggested that childhood leukaemia may be the abnormal outcome of a common infection. Rare events caused by common environmental events such as infections are likely to be influenced by host genetic susceptibility. We have therefore investigated whether immunogenetic susceptibility contributes to the risk of childhood common ALL (c-ALL). In this preliminary study, we report that children with c-ALL (n = 63) carry the HLA-DPB1 locus allele *0201 twice and nearly three times more frequently than adult (n = 92; relative risk (RR) = 2.9, P < 0.05) or infant controls (n = 82; RR = 2.1). Moreover, children with c-ALL are 3-4 times more likely than controls to be heterozygous for DPB1*0201/*0301, /*0401 and /*0402 (RRadult controls = 3.9; RRinfant controls = 2.8). These results suggest that HLA-DPB1*0201 either alone or with other DPB1 alleles contributes to the risk of childhood c-ALL, possibly by increasing susceptibility to an infectious agent. PMID- 7885044 TI - A deletion mutant of the LMP1 oncogene of Epstein-Barr virus is associated with evolution of angioimmunoblastic lymphadenopathy into B immunoblastic lymphoma. AB - The latent membrane protein 1 (LMP1) oncogene is one of the major proteins synthesized by the Epstein-Barr virus (EBV). It is expressed in Reed-Sternberg cells of Hodgkin's disease (HD), tumor cells of nasopharyngeal carcinoma (NPC), and immunoblasts of angioimmunoblastic lymphadenopathy (AILD). A particular LMP1 deletion mutant was recently identified in NPC and clinically and histologically aggressive HD. We studied two patients with AILD that subsequently progressed into immunoblastic lymphoma (IBL) in order to investigate whether the LMP1 deletion mutant was implicated in progression of AILD into IBL. Immunohistology and in situ hybridization were performed on diagnostic biopsies. DNA extracted from fresh frozen material was used for rearrangement studies and polymerase chain reaction (PCR) based amplification and sequencing of portions of the LMP1 gene. Immunohistochemistry revealed B cell origin of both cases of IBL. In the first patient clonal rearrangement of the immunoglobulin heavy-chain gene was present in IBL but not in AILD. In this patient, scattered immunoblasts of AILD and numerous tumor cells of B-IBL were shown to contain EBV transcripts (EBER1) and to express LMP1. Sequence analysis of the LMP1 gene from AILD and IBL in the first, and from IBL in the second patient, revealed identical deletions and point mutations. This LMP1 deletion mutant is identical to those which have been reported in HD and NPC. Its association with evolution of AILD into B-IBL, aggressive HD and NPC, suggests that this particular mutant is more widespread than originally thought and is clinically relevant. PMID- 7885045 TI - RAS and FMS mutations following cytotoxic therapy for childhood acute lymphoblastic leukaemia. AB - Patients who have received cytotoxic therapy for primary neoplastic disease are at an increased risk of developing secondary (therapy-related) acute myeloid leukaemia (AML) or myelodysplasia (MDS). RAS and FMS mutations have been observed in patients with AML and MDS. It has been suggested that the mutational status within these genes may be predictive of early secondary leukaemic disease. In this study we have screened 50 haematologically normal patients in complete remission from childhood acute lymphoblastic leukaemia (ALL) for activating point mutations in the RAS and FMS proto-oncogenes. Such patients may be considered at risk of therapy-related disease. Codons 12, 13 and 61 were screened in RAS and codon 969 in FMS using the polymerase chain reaction (PCR) followed by oligonucleotide hybridization (ONH). Three of the 50 patients (6%) were found to harbour N12 RAS mutations. One of these three patients (2%) had both a N12 RAS and FMS 969 mutation. Upon sequencing the RAS mutations, substitutions of serine, cysteine and aspartic acid for glycine were identified. The FMS 969 mutation was also confirmed, by sequencing, as a histidine substitution. RAS mutations were not detected in presentation samples indicating that these lesions have been somatically acquired presumably subsequent to cytotoxic therapy for the primary disease. Continued follow-up of these patients may indicate a role for these mutations in the development of secondary malignancies. PMID- 7885046 TI - Recurrent chromosomal translocations and fusion genes in leukemia-lymphoma cell lines. AB - The occurrence of defined chromosomal translocations in specific subtypes of leukemia and lymphoma strongly suggests that these structural alterations play an important role in the process of tumorigenesis. Translocations may activate nearby cellular genes involved in the control of proliferation or differentiation. One mechanism by which genes become activated or overexpressed is by their juxtaposition with the genes coding for the lymphoid antigen receptors (immunoglobulins or T cell receptors). The majority of the translocated genes appear to encode transcription factors, the expression of which might become deregulated due to the influence of regulatory elements in the antigen receptor loci. A second general type of chromosomal translocation by which proto oncogenes can be activated results in the synthesis of fusion genes. Here, chimera proteins containing portions of two different proteins are generated following exon-exon juxtaposition of two genes lying at the sites of translocation. The list of such tumor-associated fusion genes generated by specific translocations has greatly increased over the last years. A wide variety of leukemia-lymphoma cell lines have been established to act both as genetic resources and as model systems for the different disease types and stages providing an inexhaustible source of replicate material. For many translocations, DNA spanning the breakpoint was isolated by using cell lines carrying the particular abnormality. The cloning of the genes disrupted by the translocations has led to the availability of probes useful for diagnosis and monitoring of patients, eg with polymerase chain reaction (PCR) assays. Here, we review the cytogenetic and molecular data of chromosomal aberrations associated with leukemia-lymphoma and indicate a panel of human cell lines carrying such specific chromosomal abnormalities. PMID- 7885047 TI - Childhood acute lymphoblastic leukemia (ALL): sister chromatid exchange (SCE) frequency and lymphocyte subpopulations during therapy. AB - Sister chromatid exchanges (SCE) and lymphocyte subsets of children with acute lymphoblastic leukemia (ALL) were investigated during chemotherapy. The treatment followed protocol ALL-BFM-90. Children with ALL at the time of diagnosis showed statistically significant higher SCE frequencies (4.9 +/- 0.77) than healthy controls (3.6 +/- 0.93; P = 0.002). The in vivo effects of cyclophosphamide (CP) resulted in a dramatic increase of the SCE frequency (20.5 +/- 3.76). This increased SCE level of lymphocytes might reflect an instability of DNA or a deficiency of DNA repair. One could suggest that lymphocytes of children with ALL might have a higher susceptibility to harmful influences; and this could be a co factor towards the development of the malignant disease. However, immediately 1 week after the administration of CP, the SCE rate decreased. This decline of SCE frequency correlated with a severe reduction of the absolute number of T lymphocytes. The observed reduction of SCE frequency may be due to a loss of T lymphocytes, or SCE became repaired during 1 week. PMID- 7885048 TI - Complex Y chromosome aberrations are a recurrent secondary event in radiation induced murine acute myeloid leukaemia. AB - Arbitrarily primed-PCR analysis of DNA from male CBA/H radiation-induced leukaemic spleens revealed the loss of an approximately 350-bp sequence in several leukaemias. We have isolated a lambda EMBL3 C57BL/6 genomic subclone (pJB1) which hybridizes to the AP-PCR probe and is located on the Y chromosome. Southern blot analyses using the pJB1 probe indicate that the genomic sequence was deleted in five of 14 leukaemias. Cytogenetic analyses of 31 X-ray induced leukaemias in male CBA/H mice revealed, in addition to the characteristic partial deletion of chromosome 2 (28/31 leukaemias), a high incidence (16/31) of the loss of an intact Y chromosome. Comparison of the Southern blot and cytogenetic analyses of the leukaemias demonstrate a significant lack of correspondence between the loss of an intact Y chromosome and Y chromosome-specific DNA sequences, suggesting that Y chromosome aberrations are complex. Whereas partial deletion of chromosome 2 can be detected in 6% of bone marrow cells within 6-11 days of irradiation, no Y chromosome involvement was detected, indicating that Y chromosome aberrations are a late event in radiation-induced leukaemogenesis. These findings are comparable to the loss of sex chromosomes in human t(8;21) AML. PMID- 7885049 TI - MDR-related P170-glycoprotein modulates cytotoxic activity of homoharringtonine. AB - Homoharringtonine (HHT) is a new drug with antileukemic activity which is currently tested for treatment of acute and chronic leukemias, either alone or in combination with other agents. Since HHT showed a low efficacy in refractory and relapsed acute leukemia and in the blastic phase of chronic myeloid leukemia (CML) which are frequently characterized by an overexpresion of the multidrug resistance (MDR)-related P170-glycoprotein, we postulated a relationship between the poor antileukemic effect of HHT in these leukemias and the expression of P170 glycoprotein. For this reason, sensitive (LOVO109 and CEM) and MDR (LOVO DX and CEM VLB) cell lines were exposed to HHT with or without some MDR modifiers, namely, Cyclosporine A (CyA), the Cyclosporine derivative SDZ PSC 833 (PSC), and the D-isomer of Verapamil (DVRP). It was found that MDR cells were about 15 times more resistant to HHT than non-MDR cells, and that resistance to HHT was significantly decreased by all the MDR modifiers that were tested. This in vitro study showed that HHT belongs to the category of MDR-related drugs, like anthracyclines, vinca alkaloids, epipodophylline derivatives, and taxol. PMID- 7885050 TI - 5q-syndrome presenting as essential thrombocythemia: myelodysplastic syndrome or chronic myeloproliferative disorders? PMID- 7885051 TI - Correlation of cytoplasmic Ig mu (C mu) and E2A-PBX1 fusion transcripts in t(1;19) B lineage ALL: discrepancy in C mu detection by slide immunofluorescence and flow cytometry. PMID- 7885052 TI - Detection of CBF beta/MYH11 mRNA in bone marrow smears. PMID- 7885053 TI - Detection of terminal deoxynucleotidyl transferase (TdT) in nonlymphocytic leukemia by immunofluorescent (IF) assay. PMID- 7885054 TI - 2nd International Symposium on Drug Resistance in Leukemia and Lymphoma. Amsterdam, the Netherlands, March 6-8, 1995. Abstracts. PMID- 7885055 TI - The content and sources of maternal knowledge about the infant. AB - The author's purpose was to explore the knowledge that a primiparous mother acquires during the first 14 days postpartum about caretaking and personal characteristics of the infant. The study also examined the sources of this knowledge. The convenience sample consisted of 33 healthy, married, middle-class women. For caretaking knowledge, on postpartum days 1-6, mothers learned most about feeding, and on days 7-13 about administering daily care. For personal knowledge, on day 1 mothers learned most about infant physical characteristics and on days 2-13 about infant activity. Mothers acquired significantly more personal knowledge about their infant than caretaking knowledge, both daily and across the 2 weeks. Knowledge acquisition was highest during hospitalization. Maternal use of self was the dominant source for learning; however, nurses were the primary source for caretaking knowledge during hospitalization. PMID- 7885056 TI - Body experience differences of women with pregnancy-induced hypertension. AB - The author conducted this comparative study to better understand women's body experiences during pregnancies complicated by pregnancy-induced hypertension (PIH). Specifically, the study sought to determine whether women who had PIH differed from women with normal pregnancies based on their descriptions and evaluations of weight, appetite, activity, and mood experiences for four sequential time intervals of pregnancy. Using a convenience sampling strategy and semistructured interview technique, data were collected from 38 women with PIH and 23 women with normal pregnancies. The body change data were analyzed using log-linear procedures with all statistical tests conducted at the p < .05 level. Study findings indicated the pregnancies of women with PIH differed from normal pregnancy. In the context of study findings, PIH pregnancy was explored as a consequence of (a) unmet maternal dependency needs, (b) the imposition of the childbearing developmental task on an unresolved adolescent developmental phase, and (c) the binding of maternal emotional distress through selective and often dependency-symbolic body change modes and responses. PMID- 7885057 TI - Coping behaviors of young children during a chest tube procedure in the pediatric intensive care unit. AB - This descriptive correlational study examined the coping behaviors of young children experiencing a chest tube procedure in the pediatric intensive care unit (PICU) and explored specific variables that may affect coping. A developmental model of stress and coping among children provided the theoretical framework for the study. A sample of 24 children, age 2.9 to 6.8 years old, participated. Mothers completed the Dimensions of Temperament Scale-Revised and a demographic information form. In the PICU, children's coping behaviors during chest tube removal were observed and recorded on the Children's Coping Strategies Checklist Intrusive Procedures. Analysis used descriptive statistics, correlations, chi squares, t-tests, and repeated-measures analysis of variance. Findings indicate that the predominant coping behaviors represented a self-protective approach to the procedure, followed by reaching out and controlling behaviors, and information-seeking behaviors. Correlations between coping and nine temperament dimensions revealed significant results between coping and Activity-General, Activity-Sleep, and Flexibility. PMID- 7885058 TI - Involvement of protein kinase C and arachidonate signaling pathways in the alteration of proliferative response of senescent IMR-90 human fibroblasts. AB - The proliferative response of IMR-90 fibroblasts at low and high population doubling level (PDL) to protein kinase C activation has been investigated to clarify whether the reduced mitogenic responsiveness of senescent cells can be ascribed to an alteration in protein kinase C signal transduction pathway. The results show that the signaling pathway leading to DNA synthesis through protein kinase C activation, appears to be modified in senescent IMR-90 human fibroblasts. High PDL fibroblasts exhibit a different sensitivity to phorbol 12 myristate 13-acetate (PMA) and dioctanoylglycerol (diC8); high glucose reduced responsiveness to PMA only in these cells. In addition, high PDL fibroblasts are characterized by an increase in diacylglycerol (DAG) cellular mass that could contribute to the different regulatory properties of the signaling pathway. On the other hand, the ability of the cyclooxygenase inhibitor indomethacin to strikingly improve the proliferative response of high PDL cells to PMA indicates that an altered overall metabolism of arachidonate may represent a crucial step in the reduced mitogenic response involving protein kinase C activation. PMID- 7885059 TI - Age-related changes in angiotensin II-stimulated vascular contraction and inositol phosphate accumulation in Fischer 344 rats. AB - This study examined the influence of age on angiotensin II (AII)-stimulated vascular contractile responses and inositol phosphate (IP) accumulation in Fischer 344 rats. In the aorta, AII-stimulated contraction and IP accumulation were markedly reduced in 6- and 24-month-old rats compared to 1-month-old rats. There was not a significant difference in the contractile response to AII between 6- and 24-month-old rats, although IP hydrolysis showed a further decrease between 6 and 24 months. In tail artery, there were no differences in contraction and phosphoinositol metabolism in response to AII in the different ages. Losartan blocked AII-stimulated vascular contraction and IP hydrolysis in both aorta and tail artery while PD123319 did not inhibit either response. These data indicate that during maturation, there is a decline in AII-stimulated aortic contraction and IP accumulation in aorta but not in tail artery and these changes are due to altered AT1 receptor function. PMID- 7885060 TI - beta-Amyloid precursor protein (APP)-like immunoreactivity in the human sympathetic ganglia. AB - The localization of the beta/A4 amyloid precursor protein (APP) was studied in the human lumbar paravertebral sympathetic ganglia of subjects of different ages, free of neurologic disease, using combined immunohistochemistry and image analysis techniques (optic microdensitometry). To ascertain which cells displayed APP-like immunoreactivity (APP-LI), S-100 and neurofilament proteins were studied in parallel to label the supporting glial cells and the neuron perikarya, respectively. Specific APP-LI was observed labelling both neuron cell bodies and supporting glial cells independently of age. In all cases, the intensity of immunostaining was stronger in glial cells than in neurons. Moreover, the intensity of APP-LI was independent of both age and neuron size. Present results provide evidence for the presence of APP-LI in the human sympathetic ganglia, and for the absence of changes in the expression of this protein, or proteins, with aging. The functional and clinical relevance of these findings remains to be clarified. PMID- 7885062 TI - Age-related accumulation of lipofuscin in three different regions of rat brain. AB - The rate of accumulation of auto-fluorescent granules (lipofuscin) in three different regions of rat brain was investigated at various ages from very young to old animals (1, 2, 3, 6, 12 and 30-34 months of age. The accumulation of lipofuscin increased with age in the three brain regions. The first appearance of lipofuscin granules was at 8 weeks of age in the hippocampus and in the thalamus. In the case of cerebral cortex (laminae III), lipofuscin granules were first found in 3-month-old rats. The rate of lipofuscin accumulation was the highest in the hippocampus (y = 0.286x - 0.099, r = 0.963) among the three regions examined. In the case of cerebral cortex and thalamus, a slower rate of lipofuscin accumulation was observed (y = 0.072x - 0.14, r = 0.797 for cerebral cortex; y = 0.067x - 0.14, r = 0.953 for thalamus). It was noted that the most abundant accumulation and the highest rate of lipofuscin accumulation was in the hippocampus. But the rate and magnitude of lipofuscin accumulation in the hippocampus were low compared with cardiac muscles. From these results, it is suggested that brains have better protective system against oxidative stress than other organs. PMID- 7885061 TI - Effect of abscisic acid, gibberellic acid, indoleacetic acid, and kinetin on selective ribosomal cistron regulation in quiescent and senescent onion leaf base tissue. AB - Small pieces of tissue from the basal, equatorial, near-apical, and apical regions of the third turgid onion leaf base were treated (3 and 6 h in the dark) with abscisic acid (ABA), gibberellic acid (GA3), indoleacetic acid (IAA), and kinetin (K) and compared with responses in water controls. ABA inhibited the activation (increase in size and changes in morphologies from round or oval to elongated-oval and dumbbell) of major nucleolar organizer regions (NORs) in basal, equatorial, and near-apical tissue. GA3 and K activated the major NORs in the basal, equatorial, and near-apical tissue. IAA stimulated the activation of major NORs in basal tissue but inhibited their activation in equatorial and near apical tissue. No major nucleoli were activated in control or plant growth regulator-treated apical tissue. Minor NORs were not expressed in the control and plant growth regulator-treated tissue in these four locations. Actinomycin D and cycloheximide inhibited major NOR activation in equatorial control and kinetin treated tissue. We propose that ABA, GA3, IAA, and K are major NOR regulators. We infer that the basal through near-apical cells were quiescent during post-harvest storage and that the cells in the apical tissue had senesced beyond the point of no return (degeneration of the karyoskeleton) in the cellular senescence pathway. PMID- 7885063 TI - Age-dependent changes in rat liver prenyltransferases. AB - Mevalonate pathway lipids including cholesterol, ubiquinone and dolichol, are of great importance for cellular function. Many of the enzymes of this pathway are thus strictly regulated. During development of the rat, the cellular levels of certain of these lipids vary. Prenyltransferases have been investigated and it is reported here that farnesyl pyrophosphate synthase activity in rat liver cytosol decreases after birth to a lower, steady level. This decrease is not paralleled by the level of synthase protein, which shows two maxima, one immediately after birth and the other 30 days later. cis-Prenyltransferase activity is low after birth, increases continuously up to day-54 and then decreases to a low level which was maintained throughout the remainder of the study (365 days). Squalene synthase exhibits high activity after birth, but decreases during the first 100 days thereafter, and subsequently remains at the low level thus reached. In contrast to these changes in the activities of the prenyltransferases, the level of cholesterol is constant and the dolichol concentration increases continuously throughout the entire period studied. PMID- 7885064 TI - Distribution and lytic activity of NK cell subsets in the elderly. AB - Old subjects present an increased number of NK cells associated with a decreased lytic activity of isolated and cloned CD16 cells. Recently, two new surface molecules of 58 kDa, identified by the monoclonal antibodies GL183 and EB6, have been described. The presence of these molecules, which can be coexpressed on CD16+ cells allows the recognition of the NK cell subsets whose cytolytic activity is restricted to different allospecificities. This study investigated a group of old subjects to determine whether a particular distribution or a different lytic activity of NK subsets, defined by MoAbs GL183 and EB6, is involved in the altered cytolytic activity found during ageing. Further, we investigated whether the ageing process might be responsible for a restriction of the NK cell repertoire involved in the recognition of allogenic cells. We found that old and young subjects have a similar proportion of double positive and double negative GL183/EB6 cells, while in the old group single positive subsets were increased. The lytic activity of sorted NK subsets isolated from old and young subjects was similar, although double positive and double negative cells from the old presented a lower cytotoxic activity. The addition of IFN-beta or rIL-2 to the culture medium restored the lytic activity to the level found in young subjects. These data show that the decreased NK lytic activity found in the old subjects is shared out among the different NK subsets and normal aged subjects do not lose the NK repertoire found in the young. PMID- 7885065 TI - Suppression of squamous cell carcinoma in hairless mice by dietary nutrient variation. AB - In experiments involving the induction of squamous cell carcinoma in 1846 hairless mice that were maintained on a wide variety of diets, it was found that those diets with the least optimum balance of nutrients had the greatest inhibitory effect on growth of cancer. Rate of onset and severity of tumors was caused to vary over a 20-fold range by means of dietary balance alone. These experiments suggest that dietary variation in general and intentional malnutrition in particular should be given special attention in the control of existing cancer in humans. PMID- 7885067 TI - Immunocytochemical demonstration of prolactin interaction with choroid plexus in aging and acute hyperprolactinemia. AB - Prolactin (PRL) exerts a direct effect on the central nervous system, reaching the PRL-responsive brain regions via cerebro-spinal fluid (CSF). The hormone enters the CSF by a specific receptor-mediated transport mechanism that is localized on the epithelium of the choroid plexus (CP) of brain ventricles. PRL interactions with the CP in aging were examined in young (3-month) and old (27 month) female Wistar rats using immunocytochemistry (immunogold technique). The enhancement of PRL uptake by the CP in animals at both ages was achieved by the modelling of acute hyperprolactinemia. A great age-related difference was found in the intensity of immunocytochemical reaction under activated conditions, the uptake of PRL by CP being significantly higher in young animals than in old. The character of the colloidal gold particle distribution in different components of CP epithelial cells appeared to be the same in both age groups. The weakening of PRL-transporting capacity in the CP of old animals may constitute one aspect of the alteration of neuroendocrine regulation in the CP-CSF system that occurs during aging. PMID- 7885066 TI - Effect of age and caloric restriction on DNA oxidative damage in different tissues of C57BL/6 mice. AB - The objective of this study was to explore the role of molecular oxidative damage and caloric intake in the aging process. The concentration of 8 hydroxydeoxyguanosine (8-OHdG), a product of DNA oxidation, was compared in five different tissues of mice (skeletal muscle, brain, heart, liver and kidney) as a function of age and in response to dietary restriction. A comparison of 8- and 27 month-old mice indicated that the age-related increase in 8-OHdG concentration was greater in skeletal muscle, brain and heart, which are primarily composed of long-lived, post-mitotic cells, than in liver and kidney, which consist of slow dividing cells. Dietary restricted (DR) mice kept on 60% caloric intake as compared to the ad libitum-fed (AL) mice showed a lower concentration in 8-OHdG content in all the tissues compared to AL mice. The DR-related amelioration of DNA oxidative damage was greater in the post-mitotic tissues compared to those undergoing slow mitoses. Results support the hypothesis that oxidative damage to long-lived post-mitotic cells may be a key factor in the aging process. PMID- 7885068 TI - Mitochondrial activities of rat heart during ageing. AB - Some analytical and functional parameters of rat heart mitochondrial have been investigated at six different periods of ageing from 2 to 26 months. The fatty acid composition of the mitochondrial membranes reveals a percentage increase of polyunsaturated fatty acids (20:4 n-6, 22:6 n-3) up to 12 months, followed by a decrease; however, fluorescence polarization of the membrane probe diphenylhexatriene is not changed, revealing that membrane fluidity is not significantly affected. No major change in ubiquinone-9 and in cytochrome content is apparent, indicating that the relative ratio of the respiratory chain components is unmodified. Nevertheless, significant changes in enzyme specific activities are detected: NADH cytochrome c reductase and cytochrome oxidase activities increase up to 12 months, then decrease at 18-26 months; ubiquinol cytochrome c reductase exhibits a peak at 18 months, followed by a decrease. All these activities follow a similar trend during the whole life span of the rat, even though the 'maximum' is different. No significant changes have been found in ATP synthase. Succinate-cytochrome c reductase steadily increases over the whole life span. The results, showing activity decreases in the respiratory enzymes having subunits encoded by mitochondrial DNA, are compatible with the 'mitochondrial' theory of ageing. PMID- 7885069 TI - Carbon tetrachloride hepatotoxicity as a function of age in female Fischer 344 rats. AB - Severity of liver damage 24 h after intraperitoneal administration of carbon tetrachloride (0.2 ml/kg) was evaluated in female Fischer 344 rats aged 5, 14 and 28 months, i.e. in young adulthood, middle age and old age. Carbon tetrachloride induced hepatotoxicity, as judged by the leakage of hepatic enzymes into the bloodstream and the disappearance of hepatic microsomal cytochrome P450, was much less severe in old rats than in young-adult rats. For example, serum sorbitol dehydrogenase (SDH) activity following carbon tetrachloride administration was 680 mumol/min/l in old rats compared with 1710 mumol/min/l in young-adult rats, and the loss of hepatic cytochrome P450 was 25% of the total amount in old rats compared with 50% of the total in young-adult rats. Spin trapping and electron spin resonance (ESR) spectroscopy were utilized to measure the conversion of carbon tetrachloride to trichloromethyl radicals in vivo. This primary bioactivation step occurred at similar rates in female rats aged 5, 14 and 28 months. In addition, the total nonheme iron contents in livers of rats in the three age groups were similar. Thus, the age associated attenuation of carbon tetrachloride-induced hepatotoxicity was not explained on the basis of decreased bioactivation to reactive species or decreased availability of iron for promotion of lipid peroxidation. The results suggest that other factors are important determinants of age-associated changes in sensitivity to toxic chemicals. PMID- 7885070 TI - 15th Allerheiligensgesprach. Biotechnology in medical research. October 27-28, 1993. PMID- 7885071 TI - Introduction to gene technology. AB - The increased use of biotechnology for numerous categories of common products (pharmaceuticals, foods, agricultural chemicals, etc.) has an ever increasing impact on our society. In the medical/pharmaceutical field, biotechnology signifies a drastic change in the approach to drug discovery, research and development, diagnosis, and disease management. The basis of replication, transcription, translation, recombinant DNA technology, and production of altered genes are defined. Examples of biopharmaceuticals, i.e., enzymes or regulators of enzyme activity, hormones or hormone-like growth factors, cytokines, vaccines, monoclonal antibodies, and gene transfer in humans are discussed. PMID- 7885072 TI - [Ethical aspects of gene manipulation]. AB - It has become apparent that it is neither possible nor convenient to ignore all the possibilities of gene manipulation. Neither is it responsible to blindly trust in these techniques. The gains and risks must be weighed for every case. The recent amendment to the German guidelines for gene manipulation techniques does not mean that ethical discussions have ended, rather it is imperative that such discussions continue. PMID- 7885073 TI - Issues of social policy and ethics in gene technology. AB - Technical developments in the last ten years have made possible mapping and sequencing of the entire human genome, along with the possibility of treating genetic disorders by manipulating DNA. A variety of issues regarding potential uses and abuses of these technologies have become apparent. They relate to both genetic screening and gene therapy. Problems facing individuals and their families mostly revolve around rights of self-determination and of confidentiality. Health care professionals will need to design optimal systems to provide genetic counseling and to protect confidentiality of DNA data bases. Society and social institutions will need to develop policies and laws that protect the privacy of individuals whose DNA is stored in data banks. Patenting of the results of gene research remains controversial internationally. Moreover, there is concern in many quarters about society's potential abuse of gene technology for eugenic purposes. Gene therapy is now a reality. There is little disagreement on the use of gene therapy to treat genetic diseases in individuals by somatic cell therapy. There is much controversy, however, over the use of germ line cell therapy. Gene technology has contributed to the growth among a small group of influential people of the Post-Modern Movement, which is strongly antiscience and antitechnology. This movement may pose a long-term threat to future technological advances and should not be ignored. There is much outside of the laboratory that scientists, particularly molecular biologists, can do to assure a secure place for science and technology in our culture. PMID- 7885075 TI - Reform of the German Genetic Engineering Act. PMID- 7885076 TI - Legal aspects of gene technology in medical research. PMID- 7885074 TI - Public information and the ethical responsibility of the industry. AB - Biotechnology and gene technology are recognized by experts as invaluable and unique tools to find solutions to or improve many problems in health, agriculture and management of the environment, and are regarded as a driving economic force in the next century. They are, however, by large not accepted by the public and the discussion on gene technology is often emotional or even controversial. This situation is not favorable to a constructive and open debate. Science, economic forces and society coexist symbiotically and a broad debate on all aspects including the social and ethical issues of biotechnology is essential. A mutual understanding and acceptance are prerequisites to the democratic process of the elaboration of sound regulation and appropriate administration. To this aim, a task force was initiated in Switzerland by the pharmaceutical industry. Its goal is to provide information on relevant aspects of biotechnology and to participate in the dialogue with the Swiss public and politicians on critical issues like risk assessment, ethics, safety, novel food and legislation. A documentation service, teaching material, national poster campaign, exhibitions and debates on specific issues are the contributions of the industry to a fair information in favor of the improved background to an educated and open debate. PMID- 7885077 TI - Selective activation of anticancer prodrugs by monoclonal antibody-enzyme conjugates. AB - Several recent reports have demonstrated that anticancer drugs can be generated site-selectively at solid tumors by monoclonal antibody-enzyme conjugates targeted to antigens on tumor cell surfaces. The first step in this drug targeting approach involves the delivery of the enzyme conjugate to a tumor cell population. After the conjugate has localized within the tumor and cleared from non-target tissues, a relatively non-cytotoxic drug precursor (prodrug) is administered. Upon contact with the targeted enzyme, the prodrug is converted into a toxic drug. Several examples are presented to illustrate this targeting strategy. Monoclonal antibody-beta-lactamase conjugates have been developed to activate a panel of anticancer prodrugs that are mechanistically dissimilar. The antitumor activities of the monoclonal antibody-beta-lactamase conjugate/prodrug combinations exceed those obtained by systemic drug administration, and are immunologically specific. In another example involving targeted cytosine deaminase for the generation of 5-fluorouracil, it is shown that as much as 17 times more drug can be delivered within a tumor compared to when 5-fluorouracil is administered alone. The method of using targeted enzymes for prodrug activation can be extended to include prodrugs that release very potent drugs, such as palytoxin, a marine natural product, and to treat cells that have the multidrug resistance phenotype. Some of the requirements for successful therapy with this approach for cancer therapy are discussed. PMID- 7885078 TI - Genetically engineered in vitro systems for biotransformation studies. AB - In order to understand cytochrome P450-mediated metabolism of xenobiotics such as drugs and pollutants, several cell systems are genetically engineered for metabolic competence by cloning cDNAs encoding cytochrome P450 and other enzymes and by heterologous expression in bacterial, yeast, and mammalian cells. Genetically engineered cell systems are defined for the cDNA enzyme function. In conjunction with cell intrinsic properties, these genetically engineered cell systems can be used for the assessment of metabolism-dependent pharmacological and/or toxicological effects. PMID- 7885079 TI - Risk evaluation. PMID- 7885080 TI - Gene technology: chances for diagnosis and therapy. AB - In the case of a single gene defect, a number of appropriate gene probes are available for prenatal diagnosis. In some cases, knowledge of the genetic disorders enables early onset of therapy or the option for abortion. However, gene technology which enables the diagnosis should not be viewed from an ethical point of view but rather the action taken when diagnostic results are available. Gene therapy for a single gene defect still is at the early stage of development. Only a few patients have been treated in various indications. Difficult to overcome are the low frequency and unspecific integration of inserted DNA into the chromosome, lack of sufficient transcription control, and short half-life of the integrated gene. From an ethical perspective gene therapy complies with the therapeutic concept of medicine. Antisense oligonucleotides are under clinical development for blockage of the synthesis of oncogenes and viral proteins. Stability of oligonucleotides as well as selectivity for specific cells will have to be overcome for broader application. Its therapeutic application is in accordance with the ethical principles of medicine. Substitution therapies with recombinant DNA derived human proteins are in therapeutic application to replace their counterparts from native source in a safer way or for human pharmacologically active proteins which cannot be isolated from their natural source. For recombinant DNA derived proteins where the mode of action is known, short development time frames can be expected allowing for an early return on investment. The expected market potential for recombinant DNA derived pharmaceuticals in 1995 will reach 4,400 million DM. Due to their specificity, monoclonal antibodies are used for tumor imaging when labeled by 99mtechnetium or for tumor therapy when labeled by rhenium or yttrium. Both concepts are under clinical evaluation. Vaccines derived from recombinant DNA technology offer the chance of producing safer vaccines consisting of the antigen determinant only. In general, recombinant DNA technology and biotechnology offer the opportunity of providing new diagnostic and therapeutic principles of high ethical value. The biotechnical manufacturing processes used for this purpose are friendly to the environment by using raw material from renewable sources, low energy consumption, and producing biodegradable products only. In almost all cases, host cells used for manufacturing belong to the safety category 1, in which no danger is expected for the operator, the public, and the environment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7885081 TI - Clinical trials of gene/biotechnology products. AB - Gene/biotechnology products can be either physiological peptides for the purpose of substitution of deficiencies or for therapeutic purposes in superphysiological concentrations, or nonphysiological peptides, or newer biotechnology products like monoclonal antibodies. The rules for clinical trials developed so far are also valid for clinical trials with gene/biotechnology products. Nevertheless, a major challenge for the clinical pharmacologist is the species specificity of many reactions induced by gene/biotechnology products in man. In general, animal experiments may be less predictive, so there is a greater demand for human pharmacology studies. Gene/biotechnology products offer more chances for treatment of many diseases, but during the clinical trials the clinician has to always be aware of unexpected side effects. Several newer gene technology products offer superior safety as compared to older biological products like Factor VIII preparations and human growth hormone. More than 19 therapeutics produced by gene/biotechnology have already been approved by health authorities all over the world. Major clinical benefit could be shown with hepatitis B vaccine, insulin, human growth hormone, TPA, erythropoietin, GM-CSF, G-CSF, and monoclonal antibodies for immune suppression. There is also good evidence of efficacy of interferon alpha in chronic hepatitis. So far, our knowledge about cytokines is still limited. In several cancer diseases, interferons show efficacy as well as in several autoimmune diseases. Well designed clinical pharmacology studies will be important to elaborate the therapeutic potential of drugs arising from gene/biotechnology. PMID- 7885082 TI - Normal and stable transfected cancer cell lines: tools for a screening of progestogenic, antiprogestogenic and antiglucocorticoid substances. AB - Synthetic ligands for steroid receptors represent important drugs in the control of fertility and in the therapy of a large variety of endocrinological diseases. In the present study we describe the establishment of different biochemical and molecular biological screening methods. We developed a microtiter plate assay for the induction of the de novo synthesis of alkaline phosphatase in T47D cells as a suitable and fast system for the measurement of actions of progestogenic and antiprogestogenic compounds. We compared several progestogenic activities with relative molar binding affinities (RBA) to the progesterone receptor. The ED50 values for the induction of alkaline phosphatase are in good accordance with RBA to the progesterone receptor. Furthermore, glucocorticoid and antiglucocorticoid effects were measured in the stable transfected breast cancer cell line ZR75/ 763AGP-CAT. The construct AGP-CAT contains the glucocorticoid responsible element of the rat alpha-1-acid glycoprotein (AGP) gene with the bacterial chloramphenicol acetyltransferase (CAT) gene. The rat hepatoma Reuber cell line H4-II-E with the tyrosine aminotransferase gene is a further suitable marker of glucocorticoid action and was used as a second model for glucocorticoid activity. Thus, we demonstrated in three cell systems the antiprogestogenic and antiglucocorticoid activities of the model compound mifepristone. PMID- 7885083 TI - [From voluntary to compulsory psychiatric care. Legislation does not give sufficient support]. PMID- 7885084 TI - [USA approves of a new drug that decreases the craving for alcohol]. PMID- 7885085 TI - [Patients' reports on amyotrophic lateral sclerosis]. PMID- 7885086 TI - [Priority surveys: include the ethical principles in the health care law. Interview by Jan Lind]. PMID- 7885087 TI - [Better knowledge of trauma medicine is needed in Sweden]. PMID- 7885088 TI - [The last change in leadership: after the Adel and Psych-Adel reform bridges must be built]. PMID- 7885089 TI - [An alarming report on amalgam from the National Board of Health and Welfare]. PMID- 7885090 TI - [Should the guidelines on deep venous thrombosis be given the finishing touches?]. PMID- 7885092 TI - [We need useful records systems!]. PMID- 7885091 TI - [Stagnation of the records system]. PMID- 7885093 TI - [An unethical and unscientific survey on environmental health effects]. PMID- 7885094 TI - [Prevent violence!]. PMID- 7885095 TI - [New American guidelines for the treatment of stroke. A good reference book]. PMID- 7885096 TI - [The USA guidelines on stroke: quick help is the primary measure]. PMID- 7885097 TI - [Inclusion body myositis. An underdiagnosed disease with creeping muscular fatigue]. PMID- 7885098 TI - [Taurine--an amino acid with many functions]. PMID- 7885099 TI - [Prevention of accidents and infections during travel. Simple protective measures may avert the risks]. PMID- 7885100 TI - [Favourable effects of growth hormone. Therapeutic guidelines for adults with pituitary gland insufficiency. Swedish Endocrinology Society]. PMID- 7885101 TI - [Septic sacroiliitis after Cesarean section. Diffuse symptoms make diagnosis more difficult]. PMID- 7885102 TI - [Emergency care of acute myocardial infarction. Digital transmission of ECG from ambulances to intensive coronary care units]. PMID- 7885103 TI - [General practice is not public health medicine]. PMID- 7885104 TI - [A registry of health personnel--is it necessary?]. PMID- 7885105 TI - [Is carbon dioxide a contributory cause of sudden infant death?]. PMID- 7885106 TI - [Birth date on the pill box should still be indicated]. PMID- 7885107 TI - [Catch 22 in clinical research. Is application of new untested therapies ethically justifiable?]. PMID- 7885108 TI - [Ban the laser weapons! Invisible rays may cause permanent blindness in thousands of war victims]. PMID- 7885110 TI - [The 4S study is convincing--without explanation]. PMID- 7885109 TI - [Statin prevents coronary disease. The 4S study changes the therapeutic practice]. PMID- 7885111 TI - [High-dose chemotherapy in breast cancer. Promising results in combination with stem cell support]. AB - Thirty-three women with breast cancer have undergone high dose chemotherapy with autologous stem cell support at Huddinge Hospital. Twenty-eight patients had stage IV disease while five patients had disease stage II or III with involvement of > 10 axillary lymph nodes. Patients who received peripheral stem cells had a shorter duration of neutropenia than patients who received autologous bone marrow (p < 0.001). The transplant related mortality was 3 per cent. The calculated progression free survival was 39 per cent at 24 months after high dose therapy in women with stage IV chemosensitive breast cancer. Patients who got a complete remission after standard dose chemotherapy had a better survival rate than patients who got a partial remission. All women with refractory disease progressed within five months from therapy. Four out of five patients with disease stage II or III are progression free with the longest follow-up time of 46 months. High dose chemotherapy with stem cell support can be given with acceptable toxicity. The follow-up time is short but the results are promising, in particular for women who obtain a complete remission before the high dose therapy starts. PMID- 7885112 TI - [When a disaster is a fact. Kamedo analyses how the help was functioning]. AB - Kamedo (Organizing Committee for Disaster Medicine Studies) has for over 30 years compiled information on disasters in Sweden and abroad, analysed the data and published the results. The Kamedo reports supply knowledge and experience in the field of disaster medicine and form a basis for disaster medicine planning, education and research. Over 60 reports have been published so far, since 1980 including summaries in English. These summaries can be obtained from Kamedo, Swedish National Board of Health and Welfare (Socialstyrelsen), S-106 30 Stockholm, Sweden (fax +46 8 783 3287). PMID- 7885113 TI - [Thrombocytopenia in pregnant women and newborn infants. An appeal for a common care program]. PMID- 7885114 TI - [Every other traveller abroad risks diarrhea. Water and food are the most common sources of infection]. PMID- 7885115 TI - [Inquiry about the risk of malignant melanoma. One in two adults is more careful now than ever when sunbathing]. PMID- 7885116 TI - [Is human reproduction threatened? Many erratic sources in epidemiological studies]. PMID- 7885117 TI - [Lessons learnt from investigations on hepatitis B. Risk of hepatitis infection via children is underestimated]. PMID- 7885118 TI - Who is a surgeon... PMID- 7885119 TI - What will it take to stop physicians from prescribing antibiotics in acute bronchitis? PMID- 7885120 TI - Dementia, ageing, and the stress control system. PMID- 7885121 TI - Cyclospora: conquest of an emerging pathogen. PMID- 7885122 TI - Al, or the anonymity of authorship. PMID- 7885123 TI - Oral captopril versus placebo among 13,634 patients with suspected acute myocardial infarction: interim report from the Chinese Cardiac Study (CCS-1) AB - 13,634 patients entering 650 Chinese hospitals up to 36 h after the onset of suspected acute myocardial infarction (MI) were randomised between one month of oral captopril (6.25 mg initial dose, 12.5 mg 2 h later, and then 12.5 mg three times daily) or matching placebo. Captopril was associated with a non-significant reduction in 4-week mortality (617 [9.05%] captopril-allocated vs 654 [9.59%] placebo-allocated deaths; 2p = 0.3). There was a significant excess of hypotension, mostly early after the start of treatment, but no evidence of any adverse effect on early mortality (even among patients who were hypotensive at entry). Taken together with the other trials of converting enzyme inhibitors started early in acute MI, these results indicate that such therapy is generally safe and typically prevents about 5 deaths per 1000 patients treated for the first month. PMID- 7885124 TI - Is proximal demarcation of ulcerative colitis determined by the territory of the inferior mesenteric artery? AB - The sharp demarcation between diseased and normal mucosa often observed in ulcerative colitis remains unexplained by current hypotheses of disease pathogenesis. To investigate whether this demarcation occurs at the watershed of vascular territories, the colonic arterial anatomy of 10 patients with ulcerative colitis was studied by in-vitro angiography and macroscopic and histological examination of total colectomy specimens. Of the 10 perfusion-fixed colectomy specimens studied, 7 had pancolitis associated with a complete marginal artery (Arteria marginalis coli) that spanned the entire length of the large bowel. 3 specimens had sharply demarcated disease in which the marginal artery arose from the inferior mesenteric artery and ended abruptly at the point of mucosal demarcation. The colon proximal to this point was histologically normal. These findings suggest that the proximal extent of colitis is determined by the limit of the marginal artery. We suggest that some characteristic of the mucosal microvasculature in the territory of the inferior mesenteric artery, possibly embryological in origin, predisposes the dependent colon to develop ulcerative colitis. PMID- 7885125 TI - Placebo-controlled trial of co-trimoxazole for Cyclospora infections among travellers and foreign residents in Nepal. AB - Cyclospora is a coccidian (previously referred to as cyanobacterium-like bodies) that has been implicated in cases of prolonged diarrhoea. The average duration of symptoms is more than three weeks, and no specific treatment has been shown to shorten the illness. A case report suggested that co-trimoxazole may be effective. Expatriate persons with gastrointestinal complaints and cyclospora detected on examination of faeces were recruited from two clinics in Kathmandu, Nepal, between May and August, 1994. Participants were assigned in a randomised, double-blinded manner to receive either cotrimoxazole (160 mg trimethoprim, 800 mg sulphamethoxazole) or placebo tablets twice daily for 7 days. Of 40 patients included in the study, 21 received cotrimoxazole and 19 placebo. There were no significant differences between these two groups in age, sex, time in Nepal, duration or severity of illness, or presence of other enteric pathogens. After 3 days, 71% of patients receiving co-trimoxazole still had cyclospora detected, compared with 100% of patients receiving placebo (p = 0.016). After 7 days, cyclospora was detected in 1 (6%) of 16 patients treated with co-trimoxazole who submitted stool specimens compared with 15 (88%) of 17 patients receiving placebo (p < 0.0001). Eradication of the organism was correlated with clinical improvement. There was no evidence of relapse of infection among treated patients followed for an additional 7 days. Treatment with co-trimoxazole for 7 days was effective in curing cyclospora infection among an expatriate population in Nepal. PMID- 7885126 TI - Conjunctival squamous-cell carcinoma associated with HIV infection in Kampala, Uganda. AB - The incidence of conjunctival squamous-cell carcinoma in Kampala, Uganda, was steady at around 6 per million per year from 1970 until 1988, but has increased six-fold since then to 35 per million per year in 1992. Among 48 patients with conjunctival tumours seen at the ophthalmology clinic of the New Mulago Hospital from 1990 to 1991, 75% were HIV seropositive, compared with a 19% seropositivity rate among 48 matched controls (relative risk 13.0, 95% CI 4.5-39.4, p < 0.0001). The recent epidemic of conjunctival tumours in Uganda (and in neighbouring countries) appears to be largely due to the epidemic of HIV infection. Other factors that may contribute to the high incidence of these tumours in equatorial Africa may be exposure to ultraviolet light and conjunctival papillomavirus infection. PMID- 7885127 TI - Comparison of women who do and do not have amniocentesis or chorionic villus sampling. AB - Even in areas where prenatal diagnostic testing is offered at no cost to women over a certain age, uptake of testing is not complete. We have studied the factors that affect uptake in Victoria, Australia. In 1988-92, 43% of 37-39-year old women and 29% of those 40 years and over had no diagnostic testing despite their eligibility for a free test. We compared the characteristics of untested women (n = 3074) with those of tested women (2462 amniocentesis, 1575 chorionic villus sampling) by use of record-linkage between the Victorian birth register and fetal diagnosis data collection. The indication for testing was maternal age alone. Women who had had 3 or more previous births were less likely than those of lower parity to undergo testing (odds ratio 0.54 [95% CI 0.46-0.63], p < 0.001), whereas those who had had a previous termination of pregnancy were more likely to be tested than those who had not (1.52 [1.26-1.83], p < 0.001). Women born in non English-speaking countries and women who lived in rural areas were less likely to be tested. Women who gave birth in private hospitals were more likely to be tested than those who gave birth in any public hospital or at home. These data help to distinguish between issues of choice and access to diagnostic testing. Factors that hinder testing of rural women and of those from non-English-speaking backgrounds should be addressed. PMID- 7885128 TI - Rational home management of diarrhoea. PMID- 7885129 TI - Politics of euthanasia in the UK. PMID- 7885130 TI - Judicial review of refusal to fund treatment. PMID- 7885131 TI - HIV infection from donor semen. PMID- 7885132 TI - Plastic mattresses and sudden infant death syndrome. PMID- 7885133 TI - Risk of stroke in asymptomatic carotid stenosis. PMID- 7885134 TI - Risk of stroke in asymptomatic carotid stenosis. PMID- 7885135 TI - Risk of stroke in asymptomatic carotid stenosis. PMID- 7885136 TI - Risk of stroke in asymptomatic carotid stenosis. PMID- 7885137 TI - Herpesvirus-like DNA sequence in Kaposi's sarcoma from AIDS and non-AIDS patients in Taiwan. PMID- 7885138 TI - Spirochaetes in small bowel. PMID- 7885139 TI - Genetic abnormalities during transition from Helicobacter-pylori-associated gastritis to low-grade MALToma. PMID- 7885140 TI - Atropine as premedication for bronchoscopy. PMID- 7885141 TI - Vaginal birth after caesarean section. Scottish Caesarean Section Audit Group. PMID- 7885142 TI - Vaginal birth after caesarean section. PMID- 7885143 TI - Femoral arteriovenous fistula with endarteritis after angioplasty. PMID- 7885144 TI - Sensitivity of screening sigmoidoscopy for proximal colorectal tumours. PMID- 7885145 TI - A frequent hMSH2 mutation in hereditary non-polyposis colon cancer syndrome. PMID- 7885146 TI - Crossing the threshold of credibility. PMID- 7885147 TI - Crossing the threshold of credibility. PMID- 7885148 TI - Crossing the threshold of credibility. PMID- 7885149 TI - Length of intensive care and outcome after cardiac surgery. PMID- 7885150 TI - Preference, paradox, and health care reform. PMID- 7885151 TI - Pediculus humanus capitis in schoolchildren. PMID- 7885152 TI - Pediculus humanus capitis in schoolchildren. PMID- 7885153 TI - Pediculus humanus capitis in schoolchildren. PMID- 7885154 TI - Norfloxacin-induced nephrotic syndrome. PMID- 7885155 TI - Atrial versus ventricular pacing. PMID- 7885156 TI - Atrial versus ventricular pacing. PMID- 7885157 TI - Neuroleptic treatment and caudate plasticity. PMID- 7885158 TI - Increased manganese concentrations in pallidum of cirrhotic patients. PMID- 7885159 TI - Transplantation of porcine fetal pancreas to diabetic patients. PMID- 7885160 TI - Risk of relapse in multibacillary leprosy. PMID- 7885161 TI - Vitamin A supplementation during pregnancy in developed countries. PMID- 7885162 TI - Vitamin E. PMID- 7885163 TI - Vitamin E. PMID- 7885164 TI - Lithopaedion in a 92-year-old woman. PMID- 7885165 TI - Evidence of hantavirus infection in rodents and human beings from Connecticut and New York, USA. PMID- 7885166 TI - Premalignant epithelium and microinvasive cancer of the vocal fold: the evolution of phonomicrosurgical management. AB - Phonomicrosurgical treatment of premalignant vocal fold epithelium and microinvasive cancer combines principles of surgical oncology with advanced laryngoscopic microsurgical-techniques. This treatment is guided by mucosal-wave theory of voice production and strives not only to cure the disease but also to achieve optimal vocal function. Surgical techniques developed during the past two centuries have improved methods for vocal fold visualization, tissue retrieval, and tissue evaluation. Examination of the evolution of these surgical techniques reveals the incomplete convergence of laryngoscopic surgical theory with both the concept of premalignancy and the anatomical-physiological principles of voice production. This historical review, which helps to explain the lack of consensus about current treatment options, led to a series of four investigations. They were conducted with the aim of developing a laryngoscopic (phonomicrosurgical) management approach for improving the treatment of premalignant and microinvasive vocal fold epithelium. In the first of four investigations, 42 patients (each of whom had a significant smoking history) underwent microlaryngoscopic biopsy of 52 vocal fold lesions. These lesions, which were suspicious for atypia or malignancy and were confined to the musculomembranous vocal fold, were mapped according to surface involvement and depth of penetration. Review of the maps revealed that 27 of the 52 lesions involved only the superior/ventricular surface. For these patients, the entire layered vocal fold structure could potentially be preserved on the medial/vocalizing surface. Twenty-five of the 52 lesions involved both the superior/ventricular surface and the medial/vocalizing surface. No lesion involved only the medial surface. These data suggest that (in smokers) geographic localization of keratotic and erythroplastic lesions on the superior/ventricular surface of the musculomembranous vocal fold are likely to contain atypia. This characteristic facilitates the appropriate selection of patients for biopsy and may spare individuals, who have lesions resulting from hyperfunctional dysphonia and/or gastroesophageal reflux, from unnecessary biopsy. These two disorders typically result in pathology on the medial and/or posterior glottal surfaces. In order to determine whether a directed biopsy or an excisional biopsy approach is preferable for obtaining an accurate diagnosis, all specimens underwent whole mount sectioning for three-dimensional histopathological analysis. Keratosis was noted: without atypia in 14; with atypia in 27; and with carcinoma in 11. The severity of the atypia usually varied throughout each specimen. The surface appearance of the lesion was not a reliable prognosticator of the severity of dysplasia either between patients or in different areas of the same lesion; therefore, excisional biopsy and whole-mount, multiple-section histopathological analysis were necessary for obtaining an accurate diagnosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7885167 TI - Cardiovascular applications of laser technology. AB - Laser technology has been evaluated for the treatment of coronary artery disease, ventricular and supraventricular arrythmias, hypertrophic cardiomyopathy, and congenital heart disease. Developments in laser angioplasty, laser thrombolysis, transmyocardial laser revascularization, photochemotherapy, laser treatment of arrhythmias and/or laser diagnostics are directed at improving upon conventional non-laser approaches, and providing new therapeutic and diagnostic options. This review will summarize the current status of the multiple applications of laser technology for cardiovascular diagnosis and therapy. PMID- 7885168 TI - Ex vivo optical properties of human colon tissue. AB - Using a spectrophotometer equipped with an internal integrating sphere, the absorption (mu a) and the reduced scattering (microseconds') coefficients of ex vivo human colon tissues were evaluated from reflectance and transmittance measurements. Mu a and microseconds' varied from 47.7 to 1.0 cm-1 and from 14.2 to 6.2 cm-1, respectively, on passing from 300 nm to 800 nm. These results can be used to estimate the optical penetration depths when photodynamic therapy or light-induced fluorescence procedures are used. PMID- 7885169 TI - Er:YAG laser ablation of prairie dog gallbladder epithelium for the prevention of gallstones. AB - We hypothesized that laser ablation of gallbladder epithelium would prevent gallstone formation in prairie dogs. An Er:YAG laser (lambda = 2.94 microns) was used to ablate the gallbladder epithelium of 24 prairie dogs; 20 sham-irradiated and 12 non-operated prairie dogs served as controls. Prairie dogs were sacrificed at time periods of 4 days, 2 weeks, and 8-12 weeks and evaluated for the presence of gallstones and cholesterol crystals. Laser-irradiated gallbladders demonstrated a lower rate of gallstone formation at 8-12 weeks than the sham irradiated gallbladders (39% vs. 79%: P < .02). Crystal formation, however, was not different between laser-irradiated (88%) and sham-irradiated (100%) animals. The laser-irradiated group had less epithelium than the non-operated group at all time periods (P < or = .002) and compared to the sham-irradiated group at 4 days and 8-12 weeks (P < or = .001). These data suggest that laser ablation of gallbladder epithelium can reduce the rate of gallstone formation although this effect may be temporary. PMID- 7885170 TI - Clinical, histologic, and ultrastructural evaluation of tattoos treated with three laser systems. AB - We examined the response of tattoo pigments treated with three commercially available lasers: Q-switched ruby, Q-Switched neodynium:yttrium,aluminum,garnet (Nd:YAG), and the alexandrite. Tattoos applied to hairless guinea pigs and treated with the aforementioned lasers were evaluated clinically, histologically, and ultrastructurally. Clinical evaluation showed red brown, dark brown, and orange pigment responded best to the Nd:YAG laser (1064 nm). The alexandrite laser was most effective for removing blue and green pigment, the Q-switched ruby laser was most effective for removing purple and violet pigment, and the Nd:YAG laser (532 nm) removed red pigment the best. Black pigment was lightened equally with the Nd:YAG laser (1064 nm) and (532 nm) and the alexandrite laser (755 nm). No clinical scarring was observed; however, some colors turned black after treatment. Histologic and ultrastructural examination showed epidermal and dermal damage to be most evident after treatment with the Nd:YAG laser. Our study shows that certain tattoo pigments respond better to different laser systems. PMID- 7885171 TI - Erb:YAG and Hol:YAG laser osteotomy: the effect of laser ablation on bone healing. AB - Sixty-nine male Sprague Dawley rats were divided into three groups of 23 animals each and osteotomies were performed in group 1 with a power saw, in group 2 with the Erb:Yag laser, and in group 3 with the Hol:YAG laser. Two animals of each group were sacrificed 1 week, 4, 8, and 12 weeks after operation for histologic investigation, and five animals of each group at 4, 8, and 12 weeks after osteotomy for torque testing. Anterior-posterior (AP) radiographs were taken at the same time points and investigated for callus formation and development of pseudoarthrosis. All tibiae osteotomied with the Hol:YAG laser (group 3) developed pseudoarthrosis within 12 weeks and, therefore, torque testing could not be performed for this group. Biomechanical measurements of bone treated by power saw or Erb:YAG laser osteotomies, respectively, showed no significant statistical difference in the stability of bone between the two groups. Histologic examination after 1 week exhibited fibrous tissue at the site of osteotomy in rats of all three groups and additionally carbonization in rats of group 3. Saw osteotomies resulted in more callus formation than Erb:YAG osteotomies, but both techniques provoked a certain reunion within 8 weeks. Hol:YAG laser-treated osteotomies, however, exhibited formation of dense fibrous tissue, carbonization and no callus formation within 12 weeks. Radiographic pictures showed more callus formation for saw osteotomies as compared to those performed with the Erb:YAG laser. For Hol:YAG laser osteotomies pseudoarthrosis was identified also radiologically. PMID- 7885172 TI - Comparative study of the thermal effects of four semiconductor lasers on the enamel and pulp chamber of a human tooth. AB - An in vitro thermometric study was conducted on various GaAlAs semiconductor lasers emitting at wavelengths between 750 nm and 905 nm, to verify whether these lasers produce significant heating during application to tooth structure. Measurements were conducted in vitro, using a thermal camera and a thermocouple during a 60, 120, and 180 s laser exposure at energy densities between 1.5 and 2,400 J/cm2. Mean temperature changes on surface enamel were statistically significant in all groups at P < or = .05 and P < or = .01. The higher the energy density applied to a surface area, the greater the temperature rise observed using the same spot size, operation mode, and wavelength. Intrapulpal temperature elevations measured > or = 3 degrees C. An in vivo study was also conducted to determine whether perceptible stimuli are experienced by patients during this time of laser treatment and to verify results of the in vitro study. The results did not conform well with the in vitro study because of uncontrollable variables. None of the patients who received irradiation treatment described any perceptible stimuli. PMID- 7885173 TI - Effects of nimodipine and dexamethasone on low-level CO2 laser-induced release of 51chromium from canine 2C5 gliosarcoma cells. AB - Low-energy penumbral irradiation of surgical lasers may produce undesirable effects on surrounding tissues. This study used a 51Cr cell labeling technique to determine if gliosarcoma cells could be therapeutically protected prior to their exposure to low-power laser irradiation. Canine 2C5 gliosarcoma cells with intracellular 51Cr were treated with nimodipine and/or dexamethasone and then exposed to low-power levels of CO2 laser. The 51Cr was released from the cells in a dose-dependent fashion following exposure to laser energy. Correlative analysis of the data indicated that a strong direct relationship between laser fluence and 51Cr release did exist for controls and drug-treated groups with coefficients of correlation r > or = +0.90 and coefficients of determination r2 > or = 0.82. However, comparison of the data from the drug-treated and control groups found that there was no significant difference between them (P > .05). Therefore, no protective or detrimental effects were observed with the use of nimodipine and/or dexamethasone on the gliosarcoma cells as tested in this system. Further investigation is necessary in order to define the mechanisms by which low-power level lasers affect these cells. These effects do not appear to be mediated through localization of mechanisms to the cell membranes or their constituent Ca2+ channels. PMID- 7885174 TI - [Mortality trends in cerebrovascular diseases in Croatia]. AB - The research comprised all deaths from cerebrovascular diseases (CVD) in Croatia between 35 and 74 years of age over the period 1958-1987. The total number of deaths in that period increased by 40% and the number of deaths from CVD by 264%. At the same time, the rates standardized by age and sex increased by 62%. Proportional mortality rate from this disease increased from 7.1% in the year 1958 to 14.9% in 1987. The specific mortality rates over a 5-year period have shown a trend of increase in all male age groups and stagnation or decrease in females. A cohort data analysis shows a periodical and not cohort impact on mortality curve in the research period. The research shows that although mortality trends of CVD stagnated or even declined in some communities during the recent years, the secular trend for the entire country had a tendency of constant rise over the whole period of research. Therefore, the short-term prognosis predicts further increase of both the number and rate of deaths from CVD in our country. PMID- 7885175 TI - [Epidemiologic study of immunologic status of confectionary workers]. AB - Immunological and respiratory findings were studied in a group of 90 confectioners (mean age: 35 years; mean exposure: 11 years). Intradermal skin tests with different food allergens demonstrated the largest positive skin reaction to cocoa (63%), followed by chocolate (9%), cacao, nut and almond (6%) and sugar (2%). Increased IgE serum levels were found in 13.8% of the confectioners, and elevated IgM concentrations in 43.3%. The prevalence of occupational asthma and dyspnea (26.1%) in workers with positive skin tests was significantly higher than in those with negative skin tests (0%; 4.1%). There was a high prevalence of acute symptoms during the work shift. Most of these complaints were more frequent in workers with positive than in those with negative skin tests. Lung function studies demonstrated significant mean acute across-shift reductions of ventilatory capacity. Mean pre-shift FVC and FEF25 were significantly lower than predicted normal values. Pre-shift administration of disodium chromoglycate (DSCG) significantly diminished across-shift reductions for FEF50 and FEF25. Our data suggest that exposure to environmental factors in confectioneries may lead to immunological changes and the development of respiratory impairment in some workers. PMID- 7885176 TI - [Family practice and health care of the aged]. AB - The characteristics of health status of the elderly as well as the assumptions about their future tendencies indicate that primary health care for the elderly is becoming a prominent part of the overall health care. By developing the family practice, elderly people should be provided with different obligatory forms of primary health care--obligatory preventive minimum: health education and guidance, systematic medical examinations, maintenance and development of the existing functional abilities of patients such as treatment, nursing and rehabilitation in patients homes and homes for the elderly, as well as delivery of urgent medical care. The basic principle in health care for the elderly within the primary health care is an active and epidemiologic approach in a certain field, which includes the choice of family physician whose team could provide an integrated comprehensive primary health care which would be at the same time appropriate to the population health needs and also efficient and rational. PMID- 7885177 TI - [Retrospective study of echinococcosis in the Zadar region from 1960 to 1990]. AB - Seven hundred and thirty-six patients with human echinococcosis admitted to the Zadar General Hospital between 1960 and 1990 were studied. Seven hundred and seventeen patients were residents of Zadar region, while 19 were referred from other areas. There were more females (61%) than males (39%) in our study, with the majority of patients (208 individuals) being in the age group of 60 years and more. Among the examinees, the largest number were housewives (42%). 59.1 percent of echinococcus was found in the liver, 22.7% in the lungs and 3.4% in the spleen. There was a significant difference between surgically treated and untreated patients (p < 0.01) as well as between cured and uncured ones (p < 0.01). Over the studied period, there were approximately 24 new cases and 23.74, respectively. The incidence rate per 100,000 inhabitants for 1990 was 12.74. The decrease of incidence was 83.13%. The prognosis made in 1978 for specific morbidity in 1990 was 9.051 approximately 9, and 3.682 approximately 4 for realized specific morbidity. In 1990, the density of population in Zadar region was 68.2 inhabitants/km2. The number of inhabitants per 1 km2 on the mainland within the same year was 79.9, while on the islands it was 29.2 inhabitants/km2. In order to make a comparison, density of population in 1980 was calculated. The number of population amounted to 66.1 inhabitants/km2. In 1980, there were 75.8 inhabitants/km2 on the mainland, and 35.2 inhabitants per 1 km2 on the islands of the Zadar region. In 1990 the number of inhabitants on the islands decreased, although the overall number of inhabitants of that region increased. PMID- 7885178 TI - [Primary actinomycosis of the liver--case report]. AB - The liver is a rare site of actinomycotic abscess localization. A 36-year-old man admitted to the hospital because of pain under the right costal margin with skin hyperemia and edema in that region is presented. Clinical and laboratory examinations disclosed liver actinomycotic abscess. Surgical drainage was done followed by 8 months of antibiotic (penicillin) therapy. Discussed are the difficulties in diagnostic procedure and the lack of consensus in the therapeutic approach. PMID- 7885179 TI - [Analysis of justifications for prescribing drugs which must be obtained abroad]. AB - Clinical Pharmacological Expertises issued between 1986 and 1990 by the Outpatient Clinic for Pharmacotherapy at the Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Center, Zagreb were analysed. The expertises evaluated the rationale of pharmacotherapy for patients claiming the need to obtain the drug from abroad. Basis for this evaluation was the patients' medical documentation, or more rarely, physical examination of the patient. For the decision various sources were consulted. The aim of this analysis was to obtain yet another insight into the rationale of the pharmacotherapy in Croatia, and a partial overview of the quality and lack of approved drugs. Among 1293 analysed expertises, in only 46% of the patients the prescription of the drug was evaluated as rational. The administration of approved drugs was more often correct than the administration of nonapproved ones. The approved drugs whose prescription was always evaluated as unnecessary are listed, what could be of use for the renewal of the drug approval in Croatia. Among all the drugs, antineoplastic drugs were mostly appropriately prescribed, while the expertises concerning drugs for cardiovascular and nervous system were mostly negative. Expertises on certain drugs are more thoroughly discussed. Since we cannot claim that we had a representative sample of drug prescriptions; this analysis is not providing a real picture of the pharmacotherapy in Croatia, but the results may stimulate further, more systematic, evaluations. PMID- 7885180 TI - [Selection of neonates for hearing screening tests]. AB - The need for hearing screening as a first step of secondary prevention and prerequisite of an early diagnostic as well as early rehabilitation of hearing impairment is stressed. The screening is recommended in the neonatal period prior to discharge from the hospital. The author discusses which population should be screened, gives brief review of neonatal screening methods and suggests the optimal one for our conditions. The organization of follow-up is discussed, as well. PMID- 7885181 TI - [Osteoarthritis in light of the results of new research]. AB - Chondrocyte and cartilage matrix can in the course of time lose in quality due to nutritive, toxic and enzymatic influences, but also due to excessive mechanical usage so that the hyaline articular cartilage can no longer fulfill its function as a hydroelastic bumper. The results are progressive mechanical cartilage destruction and sklerosing reconstruction of the subchondral bone. The parts of the matrix that are freed by the mechanical abrasion can function as inflammatory mediators and set an accompanying synovitis going. It is this secondary synovitis that then leads to a painful manifestation of osteoarthritis. In this case, an antiphlogistic therapy is necessary, because during a secondary synovitis cytokines are set free that endanger the yet intact articular cartilage. PMID- 7885182 TI - [What is molecular medicine?]. PMID- 7885183 TI - [60 years of organized surgery in Pozega]. AB - The 60 years of organized surgery in Pozega started by Dr. Artur Horvat in the old Vucjak hospital is described. This period was designated by work, personnel and two wars occurring 50 years apart. Events and personalities dictated that time to be divided into 5 phases. The significance of that period is detailed by the use of surgical protocols, rare literature and verbal communications. PMID- 7885184 TI - [Characteristics of patients with acute myocardial infarct treated in Split from 1982 to 1992]. PMID- 7885185 TI - Inhibition of plasma membrane Ca(2+)-ATPase pump activity in cultured C6 glioma cells by halothane and xenon. AB - We have compared the effect of two inhalational anesthetics, halothane and xenon, on Ca(2+)-ATPase (PMCA) pumping activity in plasma membrane vesicles prepared from cultured rat C6 glioma cells. Halothane, at concentrations ranging from 0.5 to 1.75 vol% (equivalent to 0.5 to 1.6 MAC), significantly inhibited Ca2+ uptake (transport) by plasma membrane vesicles in a dose-related fashion. Xenon, at partial pressures ranging from 0.5 to 1.5 atm (equivalent to 0.5 to 1.6 MAC), similarly inhibited PMCA pumping activity. Additive effects on suppression of PMCA pump activity were observed when C6 cell plasma membrane vesicles were exposed to increasing partial pressures of xenon in the presence of halothane (1 vol%). Halothane also inhibited PMCA pumping in cells from two other lines of neural origin, B104 (rat neuroblastoma) and PC12 (rat pheochromocytoma). Studies described in this report support the thesis that PMCA in cells of neural origin is inhibited by quite different inhalational anesthetics at clinically relevant concentrations. PMID- 7885186 TI - Synthesis and binding characteristics of tritiated TIPP[psi], a highly specific and stable delta opioid antagonist. AB - The pseudopeptide H-Tyr-Tic psi [CH2-NH]Phe-Phe-OH (TIPP[psi]) is a delta opioid antagonist with high delta receptor affinity and unprecedented delta selectivity. TIPP[psi] was radiolabelled by catalytic tritiation of its precursor [Tyr(3',5' I2)1]TIPP[psi]. The resulting radioligand, [3H]TIPP[psi], had a specific activity of 1.77 TBq/mmol (47.9 Ci/mmol) and showed high stability against enzymatic degradation. [3H]TIPP[psi] binding to rat brain membranes was saturable and Scatchard analysis indicated a single binding site with a Kd of 0.98 nM and a Bmax of 105.4 fmol/mg. A study of [3H]TIPP[psi] binding displacement by various receptor-selective opioids showed the expected rank order of potency (delta >> mu > kappa). [3H]TIPP[psi] represents an excellent new radioligand for delta receptor labelling studies in vitro and in vivo. PMID- 7885187 TI - Modulation of alpha 1-adrenergic contractility in isolated vascular tissues by heptanol: a functional demonstration of the potential importance of intercellular communication to vascular response generation. AB - After years of intensive investigation, the mechanism(s) underlying syncytial vascular smooth muscle responses both in vitro and in vivo is still poorly understood. Neither perivascular innervation nor regenerative electrical events appear sufficient to coordinate responses among vascular smooth muscle cells in many blood vessels. The implication of these observations is that another mechanism is required for organizing syncytial vascular responses. Although gap junctions are ubiquitously distributed among vascular wall cells throughout the vascular tree, their contribution to the modulation of vasomotor tone is still considered controversial. Resolution of the long standing debate awaits a clear demonstration that gap junctions modulate contraction or relaxation responses to vascular smooth muscle. Despite the absence of specific gap junctional uncoupling agents, it has still been possible to identify reasonable experimental conditions under which the contribution of gap junctions to contractile responses in isolated vascular tissues could be evaluated. Studies in isolated preparations known to contain gap junctions have indicated that alpha 1-adrenergic receptor mediated contractile responses of diverse isolated vascular tissues, are significantly modulated by selective disruption of intercellular communication with the well studied lipophilic uncoupling agent heptanol. Interpretation of these pharmacological studies is explicitly dependent on the selectivity of the uncoupling actions of heptanol. Considerable experimental evidence suggests that, at the concentrations used, in the preparations thus far examined, heptanol does indeed have selective uncoupling actions. In fact, recent experiments provide empirical support for an operational definition of the selectivity of heptanol, and a functional role for gap junctions in modulating contractile responses in isolated vascular tissues. The operational definition states only that there exists a narrow, albeit identifiable, concentration range over which it is reasonable to assume that the effects of heptanol are primarily related to its uncoupling actions on gap junctions. The functional role for gap junctions is defined by their requisite contribution to tension development during contraction of isolated tissues. Experimentally, this can be visualized as a significant diminution in the contractile responses of isolated vascular tissues in the presence of selective uncoupling heptanol concentrations. Thus, a cogent interpretation of available data is that they provide compelling indirect evidence for a principle role of gap junctions in modulating the alpha 1 adrenergic contractility of isolated vascular tissues. PMID- 7885188 TI - Asymmetric mitoses revealed by AgNORs in developing rat blood cells. AB - Immature cells of erythroid as well as granulocytic series were studied in rat hemopoietic bone marrows to provide a basic information on the asymmetric distribution of AgNORs in anaphases and telophases of these cells. The results clearly demonstrated that such asymmetric mitotic divisions with respect to the distribution of AgNORs to future daughter nuclei represent a regular phenomenon in the course of erythroid as well as granulocytic maturation and thus are not limited to neoplastic cells in which this phenomenon was described previously. PMID- 7885189 TI - The microphotohemolytic response of erythrocytes is altered by streptozotocin induced diabetes and copper deficiency in rats. AB - Microphotohemolysis is a new technique that has been used to determine the presence of alterations in the erythrocyte membrane. The method involves light activation through a microscope of a fluorescent dye-erythrocyte-buffer solution in a hemocytometer. The interaction of the light and dye result in the generation of toxic oxygen products which attack the membrane allowing water to enter the cell. As hemolysis occurs the optical density of the microscopic field decreases and this is recorded for later quantitation with an image analysis system. Maximal effect, time to half maximal effect and the slope of the hemolysis curve are determined. The goal of this study was to determine if microphotohemolysis could be used to detect differences in erythrocytes from animals with altered physiological states such as hypercholesterolemia, diabetes, and copper deficiency. These are conditions that alter the lipid or protein structure of the erythrocyte membrane and/or the antioxidative capacity of the erythrocyte. There were no effects of hypercholesterolemia on the microphotohemolytic response of the erythrocyte. Streptozotocin-induced diabetes resulted in a decreased maximum effect, a significant shift of the hemolysis curve to the right (increased T 1/2) and a significant decrease in the slope of the hemolysis curve. Copper deficiency resulted in a significant decrease in the slope of the hemolysis curve. These results in diabetes and copper deficiency are consistent with an altered protein structure in the erythrocyte membrane that occurs in these conditions. The data demonstrate that this technique may be used to detect differences between normal and altered erythrocytes. As such, it could be useful in monitoring the course of a disease or its treatment. PMID- 7885190 TI - Insulin-like growth factor-1 is not mitogenic for the Walker-256 carcinosarcoma. AB - This study was designed to determine whether intravenous infusion of recombinant human insulin-like growth factor 1 (IGF-1) stimulates tumor growth. In order to determine the potential interaction between nutrition and IGF-1 administration the study was conducted in fasting rats and during continuous feeding by total parenteral nutrition. Tumor cell cycle kinetics including labeling index, DNA synthesis time, cell cycle time in Go/G1, and G2/M in the total cell cycle, and potential doubling time were determined by flow cytometry after in vivo pulse labeling the rats bearing the Walker-256 Carcinosarcoma with 5'-bromo-2' deoxyuridine (BrdUrd). The results show that IGF-1 treatment has no significant effects on the proliferative characteristics of the tumor model regardless of the feeding status of the animal. This study provides preliminary cell-cycle kinetics data on the short-term effect of IGF-1 on tumor growth. Failure to show a significant effect of IGF-1 on the proliferative characteristics of the tumor suggests that IGF-1 may be given to cancer patients in amounts sufficient to promote weight gain without deleterious stimulation of tumor proliferation. PMID- 7885191 TI - Drosophila GABA-gated chloride channel: modified [3H]EBOB binding site associated with Ala-->Ser or Gly mutants of Rdl subunit. AB - The non-competitive blocker site of the GABA-gated chloride ion channel in normal susceptible strains of Drosophila melanogaster and simulans binds 4-n-[3H]propyl 4'-ethynylbicycloorthobenzoate ([3H]EBOB) at specific sites with KdS of 1.6-1.9 nM and BmaxS of 171-181 fmol/mg protein. This specific binding of [3H]EBOB is strongly inhibited by: a large number and variety of insecticidal channel blockers at 20 nM (lindane, alpha-endosulfan, dieldrin, 12-ketoendrin, fipronil, and a representative bicycloorthobenzoate and dithiane) or 200 nM (picrotoxinin); the insecticidal channel activators avermectin and moxidectin at 20 nM; muscimol at 30 microM and GABA at 300 microM. Cyclodiene resistance in D. melanogaster has been attributed to a mutation resulting in an Ala302-->Ser replacement in the Rdl GABA receptor subunit and in D. simulans to an homologous Ala-->Ser or Gly replacement. These mutations are shown here to greatly reduce [3H]EBOB binding, i.e. lower affinity and apparent number of binding sites. The Ala-->Ser replacement with both melanogaster and simulans almost always reduces the potency in inhibiting [3H]EBOB binding of each of eight channel blockers and of muscimol and GABA. The Ala-->Gly replacement in D. simulans is generally less effective than the Ala-->Ser modification in reducing sensitivity to the channel blockers and to muscimol and GABA. The channel activators avermectin and moxidectin usually retain their inhibitory potency in the Rdl subunit mutants. Thus, it appears that replacement of Ala by Ser generally modifies the non-competitive blocker site and its coupling to the GABA-recognition site with less effect on the channel activator site. In contrast, the Ala-->Gly replacement has less impact in protecting the chloride channel from the action of insecticidal blockers. Each of the resistant strains has the same level of resistance to the lethal action of the five channel blockers examined but none to avermectins and muscimol. PMID- 7885192 TI - Long-term sensitization to the behavioral effects of naltrexone is associated with regionally specific changes in the number of mu and delta opioid receptors in rat brain. AB - Enhanced sensitivity to some of the behavioral effects of the opioid antagonist naltrexone (NTX) develops following once-weekly injections of cumulative doses of the drug. Rats treated with this regimen of NTX injections show enhanced sensitivity to the operant response rate decreasing effects of NTX and NTX induced salivation. The enhanced sensitivity is long-lasting and appears to be produced through conditioning processes. We have conducted saturation binding assays to assess possible changes in the number and affinity of mu and delta opioid receptors in cortical, midbrain and hindbrain membrane preparations from Long-Evans rats treated once weekly for 8 weeks with cumulative doses of the drug (1, 3, 10, 30 and 100 mg/kg). 3H-DAMGO (0.5-21 nM) and 3H-pCl-DPDPE (0.04-4 nM) were used to characterize mu and delta receptors, respectively. NTX treatment had no effect on 3H-DAMGO binding in cortex, but decreased binding in midbrain and increased binding in hindbrain relative to saline-treated controls. Saturation analyses revealed that these differences reflected changes in the number, but not the affinity of mu receptors. NTX treatment also increased the amount of 3H-pCl DPDPE bound to delta receptors in midbrain and hindbrain, but not in cortex. Again, these changes were due to changes in the number of receptors. Thus, chronic NTX differentially affects the number of mu and delta opioid receptors in various brain regions. PMID- 7885193 TI - Systemic cytokine administration can affect blood-brain barrier permeability in the rat. AB - The aim of the present study was to clarify the effect of intracarotid injection of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on the permeability of the blood-brain barrier (BBB) in the rat. A regional blood-to-brain transfer constant (Ki) for [14C] alpha-aminoisobutyric acid ([14C]AIB) and the cerebral residual blood volume were calculated 10 min following administration of cytokines (CKs; 1000 U/rat). The injection of IL-2 and IL-6 (but not of IL-1 beta) induced a significant enhancement of Ki values for [14C]AIB within several brain areas; conversely, when the rats were given TNF-alpha, a striking decrease in BBB permeability was observed. The cerebral regional blood volumes appeared significantly lower in the rats injected with IL-6 than in the control animals, but markedly increased following TNF-alpha administration. Our findings confirm the ability of some CKs to affect the permeability of the BBB and/or to act, probably indirectly, as vasomodulator agents of the cerebral microvessel endothelium. PMID- 7885194 TI - Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes. AB - The affinity of morphine, codeine, dihydrocodeine and their glucuronides for mu-, delta-, and kappa-opioid receptors was investigated. Binding was studied on guinea-pig brain homogenates with [3H]DAMGO, [3H]DPDPE, and [3H]U69593. The substitution of the free phenolic group of morphine caused a decrease in binding at opioid receptors without affecting the mu/delta-ratio nor that of mu/kappa. Glucuronidation of the 6-hydroxyl group of morphine, codeine or dihydrocodeine did not affect the affinity to mu-receptors, slightly increased the affinity for delta-receptors and reduced the affinity for kappa-receptors. The 6-glucuronides possess a decreased selectivity for mu-receptors over delta-receptors whereas that for mu- over kappa-receptors was increased. It is concluded that chemical variations at 3- and 6-position of morphine independently affect the affinity to opioid receptor subtypes. PMID- 7885195 TI - [The appearance and progression of the human immunodeficiency virus epidemic in sub-Saharan Africa]. PMID- 7885196 TI - [Hantavirus: a new pandemic?]. PMID- 7885197 TI - [Afghanistan. Between archaism and post-modernism]. PMID- 7885198 TI - [Epilepsy in a tropical setting]. PMID- 7885199 TI - [Drugs: vital necessity, illusion or business?]. PMID- 7885200 TI - [Rheumatology in black Africa: for whom, for what?]. PMID- 7885201 TI - [A nosocomial epidemic of Salmonella mbandaka which produces various broad spectrum beta-lactamases: preliminary results]. AB - During a nosocomial epidemic of Salmonella mbandaka in Algeria, 99 strains were isolated from specimens. Study of 22 of them revealed minimum inhibiting concentrations ranged from 4 to 32 micrograms/ml for cefotaxime, 2 to 32 micrograms/ml for ceftazidime and 2 to 16 micrograms/ml for ceftriaxione. The mechanism underlying resistance was enzymatic with production of broad-spectrum beta-lactamase enzyme. Clavulinic acid at a dose of 2 micrograms/ml restored the activity of hydrolyzed beta-lactamases. Resistance to all antibiotics including cefotaxime was due to a single plasmid structure. The plasmid did not belong to any known compatibility group. All strains studied contained a plasmid of 26MDa and produced TEM-1 and TEM-2 beta-lactamases. Strains resistant to cefotaxime also synthetized a broad-spectrum beta-lactamase derived from TEM. PMID- 7885202 TI - [Aspects of sexually transmissible diseases in young children in Burundi: gonorrhea caused by sexual abuse]. AB - The purpose of this study was to demonstrate the existence of sexually transmitted diseases secondary to sexual abuse inflicted on young infants in Black Africa. A total of 230 files involving infants presenting leucorrhea or urethral discharge were reviewed in Bujumbura (Burundi) to select only cases with bacteriologically documented gonorrhea. A total of 2 such cases were identified during the period from 1987 to 1992. There were 20 girls and 5 boys with a mean age of 6.4 years. In 4 cases, rape was proven. In 9 cases the contaminator could not be identified, but in 12 cases medical and legal evidence showed that the alleged authors of sexual abuse was a domestic employee at the child's home. These findings indicated that sexual abuse in children is not an uncommon occurrence in Black Africa and often leads to gonorrhea. The consequences of such abuse are aggravated by the epidemic of human immunodeficiency virus. The authors recommend a practical approach that should be taken whenever sexual abuse is suspected in these countries. PMID- 7885203 TI - [A case of nasal entomophtoral phycomycosis observed in an arid African region (Somalia)]. AB - On the African continent, rhinophycomycosis entomophtorae, a deep mycosis due to Conidiobolus coranatus, has been encountered mainly in wet forest areas. Only one case, which involved a Tchadian, has been reported in a dry zone. The present report describes a case observed in a 30-year-old Somalian, who lived all his life in the rural zone of Dinsoor where the climate is hot (temperature between 22 degrees C and 30 degrees C) and dry (annual rainfall less than 400 mm). In this patient, diagnosis was based on the presence of a characteristic bifocal deformation of the central region of the face and on histological findings typical of rhinophycomycosis entomophtorae. This case underlines the fact that this deep mycosis can occur outside of wet forest areas in Africa. Thus practitioners should not rule this diagnosis out simply on the basis of climatic conditions. PMID- 7885204 TI - [Typhoid perforations: experiences in a surgical setting in Cameroon. Apropos of 49 cases]. AB - Over a period of 3 years, 49 typhoid perforations of the small intestine were treated at Yaounde Central Hospital. These 34 men and 15 women with a mean age of 29.6 years presented sthenic peritonitis in 20 cases and more difficult to diagnose asthenic peritonitis in 29 cases. The perforation was always located at the end of the ileum and was single in 40 cases, double in 6 cases and triple in 3 cases. Surgical management in association with intensive care and multiple agent antimicrobial therapy consisted in sleeve resection in 29 cases, resections with an exteriorized anastomosis in 15 cases, and ileocolonic intubation in 5 cases. The postoperative complications were suppuration of the wall (n = 4), intestinal fistula (n = 3), evisceration, and residual abscess. There were 9 deaths (18.4%) including 4 after sleeve resection and 5 after resection with an exteriorized anastomosis. On the basis of this experience, the authors describe the diagnostic difficulties posed by typhoid perforations, discuss surgical techniques proposed in the literature, and emphasize the value of sleeve resection. PMID- 7885205 TI - [Angiofibroma of the nasal fossae: apropos of 12 cases observed in Mali]. AB - Over a period of 2 years, 12 cases of angiofibroma of the nasal fossae were observed in an otorhinolaryngology department in Bamako. The classical female sex bias attributed to this disorder which involved patients under 40 years of age in 10 cases was not found. Also in contrast with usual observations, the lesion was located in the septum in only one third of cases. In all cases management was performed on an outpatient basis and diagnosis was confirmed by histology. All patients underwent excision of polyps by the endonasal route under local anesthesia. In 2 patients with septal angiomas, electrical cautery did not suffice to control bleeding and had to be associated with abrasion from the submucosal to the sub-perichondral area. This African series shows that simple and rapid management of angiofibromas of the nasal fossae prevents complications which could be particularly severe in tropical regions. PMID- 7885206 TI - [Results of an open fixation treatment of 131 fractures of the femoral diaphyses in a Congolese hospital setting]. AB - From 1987 to 1991, 196 fractures of the femoral diaphysis were treated at the University Hospital Center of Brazzaville. A retrospective perusal of the files of these patients produced 131 analyzable cases, all treated by open osteosynthesis using either screw-attached plates (n = 84) or nails (n = 47). The overall infection rate was 5.4% (7/131). This rate was 5.9% (5/84) using screw attached plates and 4.2% (2/47) using nails, i.e. only slightly higher than in the literature. Bone fixation was successful in 90% of cases. Mechanical complications (11.4%) were due mainly to technical errors during the initial fixation. With a follow-up of 3 years, analysis according to the criteria of GENESTE showed that open osteosynthesis of fractures of the femoral diaphysis in an African orthopedic department led to 90% of good (32%) and excellent (58%) results. In this African series, the main problem was the initial fixation. PMID- 7885207 TI - [Cardiac involvement in human immunodeficiency virus infection]. PMID- 7885208 TI - [Cytokines and malaria]. PMID- 7885209 TI - [Public health in Afghanistan. Searching for strategy, desperately]. PMID- 7885210 TI - [Isolated medical practice overseas. Better collection of clinical, imaging and laboratory data]. PMID- 7885211 TI - [Prolonged treatment of recurrent neurocysticercosis using sequential doses of albendazole and praziquantel]. PMID- 7885212 TI - [Is there a revival of a focus of cutaneous leishmaniasis in Garoua, North Cameroon?]. PMID- 7885213 TI - [Epidemiologic and prophylactic deductions in the bacteriologic studies of strains of Vibrio cholerae (O:1) isolated in Rwanda]. PMID- 7885214 TI - [Wide variations in the prevalence of hepatitis C virus infection in central Africa]. PMID- 7885215 TI - [Malignant non-Hodgkin's lymphoma revealed by cardiac involvement. Apropos of a case]. PMID- 7885216 TI - [Morbidity and mortality of appendicitis in a topical setting (apropos of 120 cases of appendicular peritonitis)]. PMID- 7885217 TI - Review of postoperative pharmacological infusions in ischemic skin flaps. AB - No single drug has yet been found which can overcome the inflammatory and microvascular changes which occur in a skin flap after ischemia-reperfusion. Nevertheless, the continued failure of approximately 7% of all free flap transfers clinically suggests that there may be a place for pharmacological intervention at the time of threatened flap failure. To date, plastic and reconstructive microsurgeons have been reluctant to use drugs because of the mass of conflicting evidence emanating from the plastic surgery literature. However, scientists and surgeons now have a clearer understanding of the problems arising in ischemia-reperfusion. Multi-acting drugs which can inhibit most of the important inflammatory changes would be the ideal. This review considers some of the historical developments in the pharmacological treatment of ischemic flaps in the past decade and looks to the future when pharmacological infusions may be part of the routine for salvaging failing skin flaps. PMID- 7885218 TI - Cold stored femoral vessels as microvascular allografts: a preliminary study. AB - Cold stored femoral arteries or veins have been reinserted successfully as autografts into rabbits. The present study examines whether grafting with cold stored vascular allografts is equally successful. Rabbit femoral arteries and veins were stored at 4 degrees C for 4 weeks before insertion as allografts into unrelated animals. Three weeks after insertion into the femoral artery all venous allografts and 80% of arterial allografts were patent, but patency of both graft types declined over the next few weeks. A small number of cold stored venous allografts when inserted into the femoral vein occluded within 3 weeks. No histological evidence of rejection was apparent. The findings suggest that cold stored vascular allografts could be used successfully as an arterial "prosthesis" to support free flaps where relatively short term patency is required until the flap can establish sufficient peripheral inset to survive in its own right. This technique could be applied when autologous veins are not available or not justified. PMID- 7885219 TI - Immediate and short-term effect on arterial flow of clamping or stripping one vessel of a two vessel limb in a dog model. AB - The effect on distal blood flow in a 2 vessel limb of clamping one of the vessels or resecting it over a length is not known. Commonly this situation occurs clinically, for example, following lacerations to the radial or ulnar artery or as a result of removing a radial or ulnar artery flap. In a dog model established to mimic these clinical circumstances, a 2 vessel limb was created in which one vessel carried two-thirds of the total flow and the other one-third. Electromagnetic flow recordings were taken to measure the changes in flow in one vessel when the other was clamped or resected. Contrary to expectation, when one vessel was occluded the flow in the opposite vessel both immediately and for the following 30 minutes increased but remained well below the combined flow of 2 unclamped vessels. No increased flow was recorded in the dominant vessel when the smaller vessel was clamped, while an approximately 25% increase in flow was recorded in the smaller vessel when the larger one was clamped. This represents a reduction in total distal blood flow of one-half of the preclamping levels. Clamping of the vessel or its resection over a length resulted in the same degree of alteration in flow in the opposite vessel. The sacrifice of a dominant vessel in a 2 vessel limb whether by simple ligation or by radical stripping as for free tissue transfer significantly decreases distal flow in that limb at least in the immediate and short term.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885220 TI - Experimental study and clinical observations on hypertrophy of vascularized bone grafts. AB - In order to understand the mechanisms involved in the hypertrophy of vascularized bone grafts, a series of animal experiments were carried out and 32 clinical cases were studied. A defect in the tibial shaft was created in puppies and the ipsilateral fibula was transferred into the medullary cavity of the tibia with the anterior tibial artery and vein. The same procedure was performed on a control group but without vessel supply. Radiologically, in the vascularized group mild hypertrophy in the fibula was seen at 2 weeks, became marked by 4 weeks, but in no case did the thickening (hypertrophy) of the graft ever exceed the diameter of the recipient tibia. The control group did not show hypertrophy but fracture callus formed in the recipient tibia at both ends of the graft. On histological evaluation no reactive bone formation was evident in the control group but some reactive bone formation was seen in the vascularized group just beneath the periosteum. There was no change in the periosteum itself. In the clinical cases 47% of patients showed hypertrophy. Hypertrophy was noted mainly in the fibulae but rarely in other bones such as ilium or rib. The important factors were age and good vascularity of the grafted bone. During the period of study, weight-bearing was eliminated, so that the effects of mechanical force did not explain hypertrophy. We conclude from these studies that true hypertrophy is an essentially different process from reactive callus which forms normally in response to fracture healing. Vascularized bone grafts show remarkable hypertrophy of the grafted bone, but the exact mechanism is ill defined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885221 TI - Bernard O'Brien: the microsurgical transfer of immature bone. AB - Bernard O'Brien was one of the pioneers of vascularized epiphyseal plate transfer. His clear understanding of the wide array of potential applications for reconstructive microsurgery stimulated his interest in the transfer of growing long bones. Investigations have been carried out in his laboratory since the earliest days of skeletal free tissue transfers. This paper describes the work done with epiphyseal plate transfers in O'Brien's laboratory. Research from other centers is then reviewed. Finally, the experience with clinical application is described. PMID- 7885222 TI - Heterotopic vascularized growth plate transfer in juvenile dogs. AB - Prior animal studies of vascularized epiphyseal transfers placed growth plates in 2 bone systems where the independent growth of epiphyses and their response to altered stresses has been difficult to assess. This study assessed growth of vascularized ulnar epiphyses transferred to the ipsilateral humerus of 12-week old puppies. Growth was permitted by a specially designed extensible plate. Control groups showed that humeral dissection, osteotomy and ostectomy alone do not stimulate growth. In 4 puppies initial growth of the transferred epiphysis was seen but late collapse and formation of bridging callus occurred so that overall humeral length at maturity was not significantly different from control humeri. Physical forces inherent in heterotopic transfer may preclude long term growth of transferred epiphyses particularly in sites of higher relative load. The extensible plate used here may be a useful device in the fixation of transferred epiphyses with growth potential. PMID- 7885223 TI - Microvascular reconstruction of the upper extremity with the rectus abdominis muscle. AB - Large soft-tissue defects of the upper extremity are difficult to reconstruct. Defects in 21 patients (15-75 years old) were treated by free tissue transfer of the rectus abdominis muscle. The defects were the result of trauma or resection of tumor and measured more than 15 x 15 cm. The muscle was transferred on the inferior epigastric pedicle and covered with a skin graft within 48 hours. All transfers were successful, and early soft-tissue healing occurred. This procedure offers the advantages of easy positioning, large donor vessels, and a highly vascular soft tissue reconstruction. The long-term functional and cosmetic results have been excellent. PMID- 7885224 TI - Biosynthesis and functional role of haem O and haem A. AB - Haem O and/or haem A are specifically synthesized for the haem-copper respiratory oxidases. A 17-carbon hydroxyethylfarnesyl chain at the pyrrole ring A of the haems seems essential for catalytic functions at the oxygen-reduction site. The discovery of haem O in the cytochrome bo complex from Escherichia coli was a breakthrough in the studies on haem A biosynthesis. Molecular biological and biochemical studies in the past three years demonstrated that the cyoE/ctaB/COX10 genes are indispensable for functional expression of the terminal oxidases and encode a novel enzyme haem O synthase (protohaem IX farnesyltransferase). It has recently been suggested that the ctaA gene adjacent to the ctaB-ctaCDEF gene cluster in Bacillus subtilis encodes haem A synthase (haem O monooxygenase). In this article, we review current knowledge of the genes for haem O and haem A biosyntheses, the location and regulation of haem O synthase, the possible enzymatic mechanism of farnesyl transfer to haem B and the possible roles of the farnesylated haems. PMID- 7885225 TI - The amino-terminal domain of the P-pilus adhesin determines receptor specificity. AB - Pyelonephritic isolates of Escherichia coli commonly express P-pili, which mediate bacterial attachment to glycolipids on epithelial cell surfaces. Three classes of P-pili have been defined, based on varying specificity for galabiose containing glycolipids. Variation in adhesive capacity is correlated with a shift in preferred host, suggesting that host tropism depends largely on detailed specificity for the globoseries glycolipids. In this study we examined the importance of the PapG adhesin in determining receptor specificity. Translational fusions were constructed between the amino-terminus of the PapG adhesin from each of the three pilus classes and a reporter protein. The binding specificity of the purified fusion proteins in vitro was identical to that seen with whole bacteria. Adherence of intact bacteria to cultured kidney cells was markedly reduced by a monoclonal antibody specific for the Class III adhesin (previously denoted PrsG), confirming the importance of the amino-terminus of PapG in mediating attachment to a receptor when presented on the eukaryotic cell surface. These results suggest that the detailed receptor specificity resides solely within the amino terminus of the PapG adhesin and is independent of the complex pilus architecture. PMID- 7885226 TI - Characterization of spo0A homologues in diverse Bacillus and Clostridium species identifies a probable DNA-binding domain. AB - Spo0A is a phosphorylation-activated transcription factor of Bacillus subtilis. It is a member of the response regulator superfamily of bacterial signal transduction proteins and controls many of the changes in gene expression that occur during the transition into stationary phase and during the initiation of sporulation. To identify the domains of Spo0A most critical for determining its structural and functional features, presumptive homologues of the spo0A gene were characterized in a collection of eight Bacillus species and six Clostridium species representing phylogenetically diverse members of these genera. An alignment of the partial or complete DNA sequences of these homologues revealed three regions of especially high conservation in the effector domain. We speculate that the most highly conserved of these corresponds to the recognition helix of a putative helix-turn-helix motif, and, therefore, represents the actual DNA-containing surface of the protein. In the case of homologues identified in Bacillus anthracis and Clostridium acetobutylicum and retrieved by polymerase chain reaction amplification, we confirmed by gene-disruption analysis that the homologue actually is required for initiation of sporulation. Apparent homologues of the B. subtilis spoIVB gene were also discovered immediately upstream from the spo0A homologues in all Bacillus and Clostridium species examined. The discovery of homologues of B. subtilis sporulation genes in these diverse species implies that the gene products required for specifying pathways of sporulation-specific gene activation and for determining key morphogenetic changes may be highly conserved and suggests that an approach similar to that undertaken here might be used as a general strategy to retrieve and compare their gene sequences. Exhaustive efforts to detect a spo0A-like gene in non-endospore formers, including close relatives of Bacillus such as Listeria and Staphylococcus, were uniformly unsuccessful, suggesting that regulation of gene activity during the transition into stationary phase mediated by Spo0A-like proteins may be exclusive to the endospore-forming bacteria. PMID- 7885227 TI - Multicopy single-stranded DNAs with mismatched base pairs are mutagenic in Escherichia coli. AB - Retrons are genetic elements that encode multicopy single-stranded DNAs called msDNAs. They are clonally distributed in Escherichia coli and retrons in different clones produce DNAs with different nucleotide sequences. msDNAs consist of an RNA molecule covalently linked to a single-stranded DNA molecule. The latter contains an inverted repeat, resulting in a stem-loop structure. In two retrons, Ec83 and Ec78, the DNA is cleaved off from the RNA. All known retrons except Ec78, have one or more mismatched base pairs in the stem-loop structure. We found that two retrons, Ec86 and Ec83, when present in high copy numbers are mutagenic. The ratios of mutation frequencies observed in Lac- indicator strains were similar to the ratios observed for a mutant defective in mismatch repair. It is known that some proteins required for mismatch repair bind to mismatched base pairs prior to carrying out repair. The similarity in the mutation frequency ratios suggested that the mutagenesis caused by msDNAs of retrons Ec86 and Ec83 might be due to sequestration of a mismatch repair protein by msDNA. Strong support for this interpretation was obtained from the finding that the msDNA produced by retron Ec78 is not mutagenic. PMID- 7885228 TI - Plasminogen, absorbed by Escherichia coli expressing curli or by Salmonella enteritidis expressing thin aggregative fimbriae, can be activated by simultaneously captured tissue-type plasminogen activator (t-PA). AB - Curli are fimbrial structures expressed by Escherichia coli that specifically interact with matrix proteins such as fibronectin and laminin. Similar structures are also expressed by Salmonella enteritidis and have been denoted thin aggregative fimbriae. Bacteria expressing curli and thin aggregative fimbriae were found to bind radiolabelled plasminogen as well as the tissue-type plasminogen activator (t-PA). By contrast, E. coli carrying a gene locus with an insertionally inactivated chromosomal curlin subunit were unable to bind the two human proteins. The purified subunit polypeptides of curli and thin aggregative fimbriae bound plasminogen and t-PA with high affinity (1 x 10(8) to 2 x 10(8) M 1). The binding of plasminogen and t-PA to curli-expressing E. coli was only partially inhibited by fibronectin and laminin. Plasminogen absorbed from human plasma by curli-expressing E. coli was readily converted to plasmin by t-PA; both plasmin and t-PA were functionally active when bound to the bacteria. A simultaneous binding of fibrinolytic proteins and matrix proteins to fimbriae of E. coli and S. enteritidis could provide these pathogens with both adhesive and invasive properties. PMID- 7885229 TI - High-frequency S-layer protein variation in Campylobacter fetus revealed by sapA mutagenesis. AB - Campylobacter fetus utilizes paracrystalline surface (S-) layer proteins that confer complement resistance and that undergo antigenic variation to facilitate persistent mucosal colonization in ungulates. C. fetus possesses multiple homologues of sapA, each of which encode full-length S-layer proteins. Disruption of sapA by a gene targeting method (insertion of kanamycin (km) resistance) caused the loss of C. fetus cells bearing full-length S-layer proteins and their replacement by cells bearing a 50 kDa truncated protein that was not exported to the cell surface. After incubation of the mutants with serum, the survival rate was approximately 2 x 10(-2). Immunoblots of survivors showed that phenotypic reversion involving high-level production of full-length (98, 127 or 149 kDa) S layer proteins had occurred. Revertants were serum resistant but caused approximately 10-fold less bacteraemia in orally challenged mice than did the wild-type strain. Southern hybridizations of the revertants showed rearrangement of sapA homologues and retention of the km marker. These results indicate that there exists high-frequency generation of C. fetus sapA antigenic variants, and that intracellular mechanisms acting at the level of DNA reciprocal recombination play key roles in this phenomenon. PMID- 7885230 TI - The pAM beta 1 CopF repressor regulates plasmid copy number by controlling transcription of the repE gene. AB - pAM beta 1 is a low-copy-number, promiscuous plasmid from Gram-positive bacteria that replicates by a unidirectional theta-type mode. Its replication is initiated by an original mechanism, involving the positive rate-limiting RepE protein. Here we show that the pAM beta 1-encoded CopF protein is involved in negative regulation of the plasmid copy number. CopF represses approximately 10-fold the transcription initiated at the promoter of the repE gene and binds to a 31 bp segment which is located immediately upstream of the -35 box of the repE promoter. We propose that CopF inhibits initiation of transcription at the repE promoter by binding to its operator. PMID- 7885231 TI - Early stages in development of the Escherichia coli cell-division site. AB - Development of the Escherichia coli cell division site was studied in wild-type cells and in non-septate filaments of ftsZnull and ftsZTs mutant cells. Localized regions of plasmolysis were used as markers for the positions of annular structures that are thought to be related to the periseptal annuli that flank the ingrowing septum during cytokinesis. The results show that these structures are localized at potential division sites in non-septate filaments of FtsZ- cells, contrary to previous reports. The positions of the structures along the long axis of the cells in both wild-type cells and FtsZ- filaments were unaffected by the presence of plasmolysis bays at the cell poles. These results do not agree with a previous suggestion that the apparent association of plasmolysis bays with future division sites was artefactual. They support the view that division sites begin to differentiate before the initiation of septal ingrowth and that plasmolysis bays and the annular attachments that define them, mark the locations of these early events in the division process. PMID- 7885232 TI - Development of the cell-division site in FtsA- filaments. AB - Early changes at cell-division sites were studied in non-septate filaments induced by growth of ftsATs mutant cells under non-permissive conditions. The positions of localized regions of plasmolysis were used as markers for the locations of partial and complete annular structures that are thought to be precursors of the periseptal annuli that flank the septum during cytokinesis. The results confirmed that these structures were localized at potential division sites and suggested a model in which older division sites play a role in the generation of new sites for future use, with each older site being used only once for this purpose. The results also suggest that the details of division-site development can profitably be studied in cells in which early events in the differentiation process are uncoupled from the septation event. PMID- 7885233 TI - High-frequency homologous plasmid-plasmid recombination coupled with conjugation of plasmid SCP2* in Streptomyces. AB - Non-transmissible derivatives of the Streptomyces multi-copy plasmid plJ101 were mobilized, by cointegrate formation, at frequencies approaching 100% (measured per recipient) by derivatives of the conjugative, low-copy-number Streptomyces coelicolor A3(2) plasmid SCP2*. Efficient co-integrate formation required that the plasmids shared at least 112 bp sequence identity, and it occurred only during conjugation. An SCP2* plasmid gene is involved in the process. Co integrates were presumably formed in the donor cells and transported to the recipient cells. This is a new phenomenon, not known in other bacteria. PMID- 7885234 TI - Identification of genes involved in the sequestration of iron in mycobacteria: the ferric exochelin biosynthetic and uptake pathways. AB - Mycobacteria produce two siderophores, mycobactin and exochelin. Mycobacterium smegmatis mutants defective in the production of exochelin were isolated using agar medium containing chrome azural S for the sensitive detection of siderophores. Cosmids of genomic libraries from M. smegmatis and Mycobacterium bovis BCG were screened for complementation of the mutation. Subcloning of the complementing M. smegmatis cosmid identified a 4.3 kb fragment required for restoring exochelin biosynthesis. Sequencing of the DNA revealed four open reading frames whose genes were named fxuA, fxuB, fxuC, and fxbA. FxuA, FxuB, and FxuC share amino acid sequence homology with the iron permeases FepG, FepC, and FepD from Escherichia coli, respectively. Deletion analysis identified fxbA as the gene required to restore exochelin biosynthesis in our mutant. Although fxbA does not share amino acid sequence homology with any of the published sequences for siderophore biosynthetic genes, it does show limited homology with the phosphoribosylglycineamide formyltransferases (GAR enzymes) and methionyl-tRNA formyltransferase over a limited region of the sequence, suggesting that fxbA may code for an enzyme which adds a formyl group in the synthesis of exochelin. A fusion of fxbA with the E. coli lacZ gene demonstrated regulation of gene expression by iron. The ability of M. smegmatis mutants to produce mycobactin in the absence of exochelin supports the hypothesis that exochelin is not a precursor of mycobactin and suggests that the siderophores have independent biosynthetic pathways. In addition, complementation of the M. smegmatis mutant with the BCG cosmid restored the synthesis of the M. smegmatis exochelin, demonstrating the use of M. smegmatis as a surrogate host for analysis of exochelins from slow-growing mycobacteria. PMID- 7885235 TI - Identification of IS1206, a Corynebacterium glutamicum IS3-related insertion sequence and phylogenetic analysis. AB - Integration of plasmid pCGL320 into a Corynebacterium glutamicum ATCC21086 derivative led to tandem amplification of the inserted plasmid (Labarre et al., 1993). One amplification event was associated with integration of an insertion sequence that we have named IS1206. Hybridizing sequences were only found in C. glutamicum strains and at various copy numbers. IS1206 is 1290 bp long, carries 32 bp imperfect inverted repeats and generates a 3 bp duplication of the target DNA upon insertion. IS1206 presents the features characteristic of the IS3 family and part of the DNA sequence centering on the putative transposase region (orfB) is similar to those of IS3 and some other related elements. Phylogenetic analysis of orfB deduced protein sequences from IS1206 and IS3-related elements contradicts the phylogeny of the species, suggesting that evolution of these elements might be complex. Horizontal transfer could be invoked but other alternatives like ancestral polymorphism or/and different rates of evolution could also be involved. PMID- 7885236 TI - Translocation of a hybrid YopE-adenylate cyclase from Yersinia enterocolitica into HeLa cells. AB - Pathogenic bacteria of the genus Yersinia release in vitro a set of antihost proteins called Yops. Upon infection of cultured epithelial cells, extracellular Yersinia pseudotuberculosis transfers YopE across the host cell plasma membrane. To facilitate the study of this translocation process, we constructed a recombinant Yersinia enterocolitica strain producing YopE fused to a reporter enzyme. As a reporter, we selected the calmodulin-dependent adenylate cyclase of Bordetella pertussis and we monitored the accumulation of cyclic AMP (cAMP). Since bacteria do not produce calmodulin, cyclase activity marks the presence of hybrid enzyme in the cytoplasmic compartment of the eukaryotic cell. Infection of a monolayer of HeLa cells by the recombinant Y. enterocolitica strain led to a significant increase of cAMP. This phenomenon was dependent not only on the integrity of the Yop secretion pathway but also on the presence of YopB and/or YopD. It also required the presence of the adhesin YadA at the bacterial surface. In contrast, the phenomenon was not affected by cytochalasin D, indicating that internalization of the bacteria themselves was not required for the translocation process. Our results demonstrate that Y. enterocolitica is able to transfer hybrid proteins into eukaryotic cells. This system can be used not only to study the mechanism of YopE translocation but also the fate of the other Yops or even of proteins secreted by other bacterial pathogens. PMID- 7885237 TI - The SphX protein of Synechococcus species PCC 7942 belongs to a family of phosphate-binding proteins. PMID- 7885238 TI - Visceral leishmaniasis in Teresina, State of Piaui, Brazil: preliminary observations on the detection and transmissibility of canine and sandfly infections. AB - A Leishmania donovani-complex specific DNA probe was used to confirm the widespread dissemination of amastigotes in apparently normal skin of dogs with canine visceral leishmaniasis. When Lutzomyia longipalpis were fed on abnormal skin of five naturally infected dogs 57 of 163 (35%) flies became infected: four of 65 flies (6%) became infected when fed on apparently normal skin. The bite of a single sandfly that had fed seven days previously on a naturally infected dog transmitted the infection to a young dog from a non-endemic area. Within 22 days a lesion had developed at the site of the infective bite (inner ear): 98 days after infection organisms had not disseminated throughout the skin, bone marrow, spleen or liver and the animal was still serologically negative by indirect immunofluorescence and dot-enzyme-linked immunosorbent assay. When fed Lu. longipalpis were captured from a kennel with a sick dog known to be infected, 33 out of 49 (67%) of flies contained promastigotes. In contrast only two infections were detected among more than 200 sandflies captured in houses. These observations confirm the ease of transmissibility of L. chagasi from dog to sandfly to dog in Teresina. It is likely that canine VL is the major source of human VL by the transmission route dog-sandfly-human. The Lmet2 DNA probe was a useful epidemiological tool for detecting L. chagasi in sandflies. PMID- 7885239 TI - Distribution of phagetype patterns of Mycobacterium tuberculosis isolated in Cuba (1987-1991). PMID- 7885240 TI - Cochliomyia hominivorax (Coquerel, 1858) and Phaenicia sericata (Meigen, 1826) parasiting domestic animals in Buenos Aires and vicinities (Diptera, Calliphoridae). PMID- 7885241 TI - Cytokine responses to dengue infection among Puerto Rican patients. AB - Recently, a strong correlation between high concentration of tumor necrosis factor (TNF alpha) in blood and severity of dengue hemorrhagic fever/dengue shock syndrome has been reported from Asia and the Pacific. We wished to determine if a similar relationship could be found in dengue patients in the Americas where adult patients with severe syndromes have been observed more frequently than in Asia where severe cases have been observed mostly among children. The concentrations of interleukin-1 (IL-1 beta) in hospitalized adult groups were significantly lower than that in outpatient adults. In contrast, the levels of interleukin 6 (IL-6) were significantly higher in hospitalized adults and children than in the corresponding outpatients. Levels of TNF alpha were higher in hospitalized children than in outpatient children or hospitalized adults. There was no significant difference in the levels of these three cytokines among hospitalized patients with or without hemorrhagic manifestations. Thus, an elevated IL-6 level was positively associated with severity of dengue infection in both children and adults, but IL-1 beta level was negatively associated with severity in adults. PMID- 7885242 TI - Comparative evaluation of a simple and sensitive assay for detection of orthomyxo and paramyxoviruses. AB - Studies were done to evaluate comparatively the traditional HA assay and a more recently introduced lectin-neuraminidase (LN) methodology in search of a simple and sensitive assay for virus detection during laboratorial diagnosis. The results proved the value of LN assay as a sensitive methodology for detection of virus particles, presenting results at least equal to those obtained by HA (hemagglutination) assay, with significant values of accumulated frequencies for LN/HA factors (ratios between LN and HA titers) higher than two. The accumulated values of frequencies for LN/HA factors as high as four were very significant, 72.7% for influenzavirus and 60.7% for Newcastle disease virus (NDV), moreover accumulated frequencies for LN/HA factors even as high as 32 were due to influenzavirus (45.4%) and NDV (7.2%) samples. After the storage period, most of those concentraded samples that even did not present HA titers could be detected through LN assay, demonstrating a lower threshold for virus detection. PMID- 7885243 TI - The use of ferromagnetic Dacron as solid-phase in enzyme immunoassays. AB - Ferromagnetic dacron is proposed as an alternative solid-phase for magnetic enzyme immunoassays. Human serum albumin (HSA) was covalently immobilized onto ferromagnetic dacron and an enzyme immunoassay was developed using anti-HSA rabbit sera. Peroxidase, o-phenylenediamine (OPD) and hydrogen peroxide were used as the enzymatic label and substrates, respectively. Best results were observed when particles of 63-100 microns (diameter) and 10 micrograms of immobilized antigen were used. Positive reactions were detected until dilutions of 1:51200 of immune sera. Its reproducibility was similar to standard ELISA. Disruption of the immunocomplexes formed and recuperation of the immobilized antigen in other immunoassays also proved to be reliable. PMID- 7885244 TI - Human papillomavirus detection in genital lesions by in situ hybridization and ultrastructural observations. AB - Detection of papillomavirus DNA in situ hybridization technique was performed in 29 symptomatic patients (6 males and 23 females) during the period of 1989-1991 at the Clinic for Sexually Transmitted Diseases, Universidade Federal Fluminense, State of Rio de Janeiro. All the male patients had condyloma acuminata. Only HPV 6/11 were found in these lesions. Clinical features in the female patients included vulvar condyloma acuminata, bowenoid papulosis, flat cervical condyloma, cervical condyloma acuminatum and cervical intraepithelial neoplasia grade II (CIN II). We also found cases of condyloma acuminata associated to vulvar intraepithelial neoplasia grade III (VIN III), as well as to vaginal invasive carcinoma. HPV 6/11 and 16/18 were found in vulvar condyloma acuminata. Mixed infection by 6/11-16/18 HPV were also seen in these lesions as well as in the patient who had cervical condyloma acuminatum. HPV 16/18 were found in the condyloma acuminatum plus VIN III and in the CIN II lesions. We have found HPV 31/33/51 in the specimen of condyloma acuminatum plus invasive carcinoma. In order to investigate the ultrastructural aspects of HPV infection in genital tissue, the biopsies of three female patients were observed under electron microscope. Mature virus particles were found in the cells of a condyloma acuminatum as well as in the condyloma acuminatum plus invasive carcinoma case. In another sample, chromosome breakages were found in the nuclei of the infected cells although no viral particles were observed. PMID- 7885245 TI - Conditions for the production and detection of Aeromonas enterotoxins. PMID- 7885246 TI - Polimerase chain reaction for the detection of Mycobacterium tuberculosis complex. PMID- 7885247 TI - Reversibility of muscle and heart lesions in chronic, Trypanosoma cruzi infected mice after late trypanomicidal treatment. AB - The effect of trypanomicidal treatment upon established histopathological Trypanosoma cruzi induced lesions was studied in Swiss mice. The animals were inoculated with 50 trypomastigotes and infection was allowed to progress without treatment for 99 days. After this period, the animals were divided in three groups, treated for 30 days with either placebo, benznidazole (200 mg/kg/day) or nifurtimox (100 mg/kg/day). These treatments induced 94 and 100% cure rates respectively as detected by xenodiagnosis and reduction of antibody levels. Autopsies and histopathological studies of heart, urinary bladder and skeletal muscle performed on day 312 after infection showed almost complete healing without residual lesions. As long periods were allowed between infection, treatment and autopsy, the results indicate that tissue lesions depend, up to advances stages, on the continuous presence of the parasite. PMID- 7885248 TI - Leishmaniasis disseminated by Leishmania braziliensis in a mare (Equus cabalus) immunotherapy and chemotherapy assays. AB - Cutaneous disseminated lesions caused by Leishmania sp. were found in a pregnant mare (Equus cabalus) from a rural city in the State of Rio de Janeiro, Brazil. Before delivering, treatment was undertaken by immunotherapy followed by chemotherapy. Histopatology and serology were performed during treatment, as well as the biochemical characterization of the parasite (L. braziliensis) that was isolated from one of the lesions. PMID- 7885249 TI - Vibrio fluvialis attachs to but does not enter HeLa cell monolayers. AB - Considering the possibility that invasiveness could be a neglected factor of virulence in Vibrio fluvialis-linked enteritis, since a dysenteric form of the disease was seen in Bangladesh, we studied 12 Brazilian strains of the organism, six clinical and six environmental, to determine whether they might be able to enter into HeLa cell monolayers or would carry plasmids incidentally involved in invasiveness. Four human and two environmental isolates attached to but did not enter into the cells. Though five strains harbored plasmids, no relationship was found between the carriage of these genetic elements and adhesiveness. PMID- 7885250 TI - Comparative chromatin analysis of Trypanosoma congolense. AB - The chromatin of Trypanosoma congolense was analyzed by electron microscopy. The chromatin is organized as nucleosome filaments but does not form a 30 nm fiber. There are five groups of histones, including a histone H1-like protein, which as a molecular weight within the range of the core histones, and is extremely hydrophilic. Weak histone-histone interaction, a typical feature of trypanosome chromatin, was found. These results are similar to those for T. cruzi and T. b. brucei, but differ significantly from those for higher eukaryotes. The results confirm the model of trypanosome chromatin, and support the theory of their early separation from the other eukaryotes during the evolution. T. congolensis is an excellent model for chromatin research on trypanosomes, because it is easy to cultivate and its chromatin has, a relatively high stability, compared to that of other trypanosomes. PMID- 7885251 TI - Adipokinetic hormone causes formation of low density lipophorin in the hemolymph of Triatoma infestans. PMID- 7885252 TI - Dengue in Brazil--situation, transmission and control--a proposal for ecological control. AB - This article discusses dengue in terms of its conceptual and historical aspects, epidemiological and clinical/pathological nature, and evolution up to the present situation in Brazil. The author discusses the ecological relationship in both the production of dengue and its control. Comparison is made between traditional dengue-control programs and a proposed socially-controlled program of an ecological nature without the use of insecticides. Stress is placed on interdisciplinary technical and scientific activity, broadbased participation by communities in discussing methodological aspects involving them, and prospective evaluation comparing the communities selected for intervention and control communities with regard to clinical and subclinical dengue cases and vector infestation rates in relation to climatic, socio-economic, and behavioural factors. PMID- 7885253 TI - Susceptibility status of Aedes taeniorhynchus to organochlorine and organophosphate insecticides. PMID- 7885254 TI - Trypanosoma cruzi: metacyclogenesis in vitro--I. Changes in the properties of metacyclic trypomastigotes maintained in the laboratory by different methods. AB - In this work we have studied the modifications in the biological properties of Trypanosoma cruzi when the parasite is maintained for a long time in axenic culture. The studies were done with a clone from an avirulent strain (Dm30L) and a non-cloned virulent strain (EP) of T. cruzi. Both parasites were maintained, for at least three years, by successive triatomine/mouse alternate passage (control condition), or by serial passage in axenic medium (culture condition), or only in the mouse (mouse condition). The comparison between parasites of culture and control condition showed that metacyclogenesis capacity was reduced in the former and that the resulting metacyclics displayed an attenuated virulence. In order to compare the virulence of metacyclics from the urine of the insect vector, Rhodnius prolixus were infected by artificial feeding with parasites of the control or culture condition. After three triatomine/triatomine passages, there was observed an almost identical biological behavior for these parasites, hence indicating that the maintenance of T. cruzi for a long time in axenic culture affects the differentiation capacity and the virulence of the parasite. Additionally, it was demonstrated that it is possible to maintain T. cruzi exclusively through passages in the invertebrate host. PMID- 7885255 TI - [Biology of Rhodnius pictipes Stal, 1872 under laboratory conditions (Hemiptera, Reduviidae, Triatominae)]. AB - Rhodnius pictipes Stal, 1872 is a silvatic species with a widespread distribution in South America, found in nine Brazilian states, naturally infected by Trypanosoma cruzi and T. rangeli. The individual rearing of this species under laboratory conditions, allowed the following biological aspects to be observed: incubation time, search for first meal after eclosion or moult, time-lapse between presentation of the blood meal and the beginning of feeding, duration of blood meal, time and place of defecation, number of blood meals, duration of each instar and adult longevity, and time required from egg to adult. PMID- 7885256 TI - Possible absence of attraction to odor in Panstrongylus megistus (Hemiptera: Reduviidae) under laboratory conditions. AB - We tested the attraction of Panstrongylus megistus odor under laboratory conditions, between males and females of this species and by individuals of each sex on recently fed virgin couples. We employed a system of choice boxes both with or without forced aeration. We observed no differences between the experimental groups with or without aeration over the stimuli in the tested situations. We also observed a clear trend among the insects to remain in the central box where they had been placed in the beginning of the tests. PMID- 7885257 TI - The cave organ of Triatominae (Hemiptera, Reduviidae) under scanning electron microscopy. PMID- 7885258 TI - Meeting on Parasites and the invertebrate vector. John D and Catherine T MacArthur Foundation, November 18-21, 1993. PMID- 7885259 TI - Metamemory, distinctiveness, and event-related potentials in recognition memory for faces. AB - A neglected topic in metamemory research is the ability of subjects to predict their own recognition performance for faces. We investigated whether subjects can make such judgments of learning (JOL) for unfamiliar faces and whether JOLs relate to facial distinctiveness, a powerful determinant of face recognition. One group of subjects made JOLs, and a second group rated the same faces for distinctiveness; subsequently, both groups tried to recognize these faces among new faces. There was significant prospective metamemory for faces that appeared to be based on facial distinctiveness. Both prospective metamemory and distinctiveness ratings related to long-lasting effects in event-related brain potentials (ERPs), closely resembling an ERP component that predicted face recognition. Therefore, the brain processes underlying JOLs, distinctiveness, and recognition memory for faces appear to be intimately related. PMID- 7885260 TI - Cross-linguistic comparisons in the integration of visual and auditory speech. AB - We examined how speakers of different languages perceive speech in face-to-face communication. These speakers identified synthetic unimodal and bimodal speech syllables made from synthetic auditory and visual five-step /ba/-/da/ continua. In the first experiment, Dutch speakers identified the test syllables as either /ba/ or /da/. To explore the robustness of the results, Dutch and English speakers were given a completely open-ended response task. Tasks in previous studies had always specified a set of alternatives. Similar results were found in the two-alternative and open-ended task. Identification of the speech segments was influenced by both the auditory and the visual sources of information. The results falsified an auditory dominance model (ADM) which assumes that the contribution of visible speech is dependent on poor-quality audible speech. The results also falsified an additive model of perception (AMP) in which the auditory and visual sources are linearly combined. The fuzzy logical model of perception (FLMP) provided a good description of performance, supporting the claim that multiple sources of continuous information are evaluated and integrated in speech perception. These results replicate previous results found with English, Spanish, and Japanese speakers. Although there were significant performance differences, the model analyses indicated no differences in the nature of information processing across language groups. The performance differences across languages were caused by information differences due to different phonologies in Dutch and English. These results suggest that the underlying mechanisms for speech perception are similar across languages. PMID- 7885261 TI - Monitoring of comprehension: the role of text difficulty in metamemory for narrative and expository text. AB - The effect of text difficulty on metamemory for narrative and expository text was investigated. In Experiment 1, we found an interaction between type of text and type of question (thematic or detailed). For readers of narrative texts, correlations between predicted and actual performance were highest for detailed questions, but this pattern was reversed for readers of expository texts. Next, text difficulty was explored as a possible factor affecting metamemory accuracy. In Experiments 2 and 3, metamemory accuracy was a nonmonotonic function of text difficulty. Subjects made remarkably accurate predictions of future performance (mean G > .6) for both narrative and expository texts that were of intermediate difficulty (approximately a 12th-grade reading level). We propose an optimum effort hypothesis, predicting greatest metamemory accuracy when the texts are of intermediate difficulty. PMID- 7885262 TI - Accepting the null hypothesis. AB - This article concerns acceptance of the null hypothesis that one variable has no effect on another. Despite frequent opinions to the contrary, this null hypothesis can be correct in some situations. Appropriate criteria for accepting the null hypothesis are (1) that the null hypothesis is possible; (2) that the results are consistent with the null hypothesis; and (3) that the experiment was a good effort to find an effect. These criteria are consistent with the meta rules for psychology. The good-effort criterion is subjective, which is somewhat undesirable, but the alternative--never accepting the null hypothesis--is neither desirable nor practical. PMID- 7885263 TI - Lexical factors in the word-superiority effect. AB - In the Reicher-Wheeler paradigm, fluent readers can identify letters better when they appear in a word than when they appear in either a pronounceable pseudoword (a lexicality effect) or a single letter (a word-letter effect). It was predicted that if both of these effects involve a lexical factor, then adult acquired dyslexic subjects whose deficit prevents access to visual word form should show disruptions of the normal effects on the Reicher-Wheeler task. The results were that dyslexic subjects as well as matched control subjects showed a lexicality effect; however, while the control subjects showed a normal word-letter effect, the dyslexic subjects showed a reverse letter-superiority effect. Both effects, however, showed a systematic variation: As performance on lexical decision improved, the subjects' performance on words in the Reicher-Wheeler task was better than that for all the other conditions. These subject correlations were replicated by using data from a second lexical decision experiment, which utilized the same words and pseudowords that were used in the Reicher-Wheeler task. In addition, an item analysis showed that the words that the subjects had discriminated correctly in lexical decision showed a significant advantage over those that they had not, as well as an improvement relative to the other conditions. These results suggest that there is a lexical factor underlying the lexicality and word-letter effects, and it is proposed that the abnormal letter superiority effect can be accounted for as the manifestation of other competing factors. PMID- 7885264 TI - When plausibility judgments supersede fact retrieval: the example of the odd-even effect on product verification. AB - In the present study, we examined the conditions that favor the plausibility judgment strategy over the retrieval strategy when we verify some statements. In particular, we examined the effect of odd-even status of numbers on subjects' verification of single-digit arithmetic problems. In Experiment 1, we explored how factors such as problem difficulty and stimulus onset asynchrony (SOA) influence this effect in adults. In Experiment 2, we present evidence that this odd-even effect is also present in elementary school children, although it varies with the age of the children, the difficulty of the problems, and the SOA. We argue that the odd-even information is helpful in arithmetic verification tasks with difficult problems early in the verification processes and that the time course of these effects differs across ages. The present results are consistent with the view that the plausibility strategy is preferred over the retrieval strategy at an early stage of processing and with information that is not quickly accessible. Finally, we discuss the implications of the present experiments for understanding of single-digit arithmetic and for understanding the more general issue of how people coordinate use of multiple strategies. PMID- 7885265 TI - The role of attention in the shift from orientation-dependent to orientation invariant identification of disoriented objects. AB - In two experiments, the naming of rotated line drawings of natural objects was examined after a training phase in which the objects were either attended or ignored. In the training phase of Experiment 1, subjects were presented with objects in a number of orientations over five repeated blocks of trials. In the center of each object, seven letters (Xs and Ts, colored red or blue) were presented in rapid succession. Half the subjects named aloud the rotated object and ignored the changing letter display (object-attend). The other half ignored the object and counted the number of red Ts, and then used this number to perform a simple multiplication (object-ignore). In the test phase, all subjects named the rotated objects. The results showed that in the first block of trials in the training phase, mean naming time in the object-attend condition increased the further an object was rotated from the upright. This effect of orientation for attended objects was much reduced in the later presentations of the test phase. In contrast, there was no such benefit of prior presentation observed for the naming of objects that had previously been ignored. Instead, a substantial orientation effect was shown for the naming of previously ignored objects, which was similar to the orientation effect observed for attended objects named in the first block. Similar results were found in Experiment 2, in which object-attend subjects in training covertly named the objects and then performed a letter count and multiplication task. In both experiments, performance on the letter count and multiplication task varied with the angle of the ignored object. The results suggest that full attentional resources must be allocated in order for orientation-invariant representations to be formed and used in the identification of rotated objects. PMID- 7885266 TI - Aging of attention: does the ability to divide decline? AB - Previous research has yielded conflicting results regarding the relationship between adult age and the ability to divide attention between two concurrent tasks. At least some of the inconsistency is probably attributable to methodological variations, such as the manner in which divided-attention ability has been assessed, how single-task performance has been considered, and the degree of control over relative emphasis placed on each task. Two experiments employing procedures sensitive to these concerns were conducted in which a speeded decision task was performed during the retention interval of a letter memory task. The results of both experiments indicated that there were relatively few age-related influences on dual-task performance vis-a-vis those on single task performance. PMID- 7885267 TI - Misinformation revisited: new evidence on the suggestibility of memory. AB - In three experiments involving a total of 623 subjects, a series of slides was shown depicting a student in a college bookstore stealing a variety of items. Next, subjects read a narrative describing the event that contained some misinformation and some neutral information about several critical details. Finally, subjects took a memory test. On this test, subjects were asked to list exemplars of 20 specified categories but were instructed not to list any items that they saw in the slide sequence. Analogous to Lindsay's (1990) adaptation of Jacoby, Woloshyn, and Kelley's (1989) "logic-of-opposition" paradigm, the tendency to report suggested details was thus set in opposition to the ability to remember the source of those details. Therefore, we interpreted failure to include suggested details as exemplars as evidence that subjects believed those details had been present in the event. Analysis of subjects' responses under opposition instructions suggests that some misled subjects come to genuinely believe that they saw items that, in reality, were only suggested to them. PMID- 7885268 TI - Is nonword repetition a test of phonological memory or long-term knowledge? It all depends on the nonwords. AB - The extent to which children's performance on tests of nonword repetition is constrained by phonological working memory and long-term lexical knowledge was investigated in a longitudinal study of 70 children tested at 4 and 5 years of age. At each time of testing, measures of nonword repetition, memory span, and vocabulary knowledge were obtained. Reading ability was also assessed at 5 years. At both ages, repetition accuracy was greater for nonwords of high- rather than low-rated wordlikeness, and memory-span measures were more closely related to repetition accuracy for the low-wordlike than for the high-wordlike stimuli. It is argued that these findings indicate that nonword repetition for unwordlike stimuli is largely dependent on phonological memory, whereas repetition for wordlike items is also mediated by long-term lexical knowledge and is therefore less sensitive to phonological memory constraints. Reading achievement was selectively linked with earlier repetition scores for low-wordlike nonwords, suggesting a phonological memory contribution in the early stages of reading development. Vocabulary knowledge was associated with repetition accuracy for both low- and high-wordlike nonwords, consistent with the notion that lexical knowledge and nonword repetition share a reciprocal developmental relationship. PMID- 7885269 TI - A dissociation in the effects of study modality on tests of implicit and explicit memory. AB - Three experiments investigated variables affecting explicit and implicit memory for study modality. Explicit memory for modality was compared with implicit memory for modality (modality-specific priming) following the study manipulation of modality and level of processing. Explicit recall of modality showed the same pattern of dissociations that has been observed between other measures of episodic memory and priming measures of memory. Manipulations of meaning at study that facilitated recognition and fragment-cued recall increased the accuracy of modality recall, but had no effect on primed fragment-completion performance. In contrast, changing modality between study and test affected fragment-cued performance, but had no effect on recognition or on modality recall. Successive tests of fragment-cued recall and modality recall were found to be highly dependent, whereas successive tests of fragment-completion and modality recall were essentially independent. The results are interpreted as evidence that (1) factors relevant to episodic memory of modality are unrelated to factors that produce modality-specific priming and (2) episodic memory for incidental attributes of an episode, such as modality of study, interacts with and is dependent upon memory for the episode as a whole. PMID- 7885270 TI - Insulin resistance and hyperinsulinemia in homozygous beta-thalassemia. AB - Insulin resistance and hyperinsulinemia have been reported in homozygous beta thalassemia before the development of diabetes. However, insulin sensitivity (SI) has never been studied in normoinsulinemic patients. Furthermore, whether hyperinsulinemia is due to increased beta-cell secretion or to decreased hepatic insulin extraction is poorly understood. We estimated SI, beta-cell secretion, and hepatic insulin extraction using the minimal model analysis of a frequently sampled intravenous glucose tolerance test (2.8 g/m2) in two groups of nondiabetic pubertal patients with homozygous beta-thalassemia (seven hyperinsulinemic and seven normoinsulinemic patients) and seven control subjects matched for age, body mass index, and pubertal stage. In both thalassemic groups, SI was reduced by approximately 40% (3.52 +/- 0.57 and 3.74 +/- 0.66 v 6.89 +/- 1.02 10(-4).min-1 [microU/mL], P = .011) and was inversely correlated with iron overload (r = -.707, P = .006). All parameters of beta-cell secretion were not significantly different in patients and controls. On the other hand, basal posthepatic insulin delivery (BDR) was more than doubled in hyperinsulinemic patients with respect to normoinsulinemic patients or controls (15.1 +/- 2.4 v 6.1 +/- 1.1 and 7.5 +/- 2.3 pmol/L.min-1, P = .012), and the same was true for total posthepatic insulin delivery ([TID] 6.3 +/- 1.0 v 2.9 +/- 0.5 and 2.9 +/- 0.7 pmol/L.240 min-1, P = .015). Hepatic insulin extraction was significantly lower in hyperinsulinemic patients than in normoinsulinemic patients or controls (49.3% +/- 9.4% v 73.0% +/- 3.7% and 77.4% +/- 3.9%, P = .011), and in patients it was inversely correlated with iron overload (r = -.829, P = .0001). In conclusion, insulin resistance is present even in normoinsulinemic patients, beta cell responsiveness to glucose is normal, and hyperinsulinemia is mainly due to decreased hepatic insulin extraction. In nondiabetic thalassemic patients, these defects are possibly related to iron overload. PMID- 7885271 TI - Increased serum D-lactate associated with diabetic ketoacidosis. AB - We hypothesized that serum D-lactate may be increased in vivo in diabetes mellitus as a result of increased glucose flux through the glyoxalase pathway and/or via hepatic ketone metabolism. Levels of D-lactate and related metabolic intermediates were measured in 30 cats with spontaneous diabetes mellitus and in one ketoacidotic nondiabetic cat. Serum D-lactate was significantly (P = .0051) elevated in cats with ketoacidosis (337.2 +/- 70.2 mumol/L) as compared with nonketoacidotic diabetic (140.3 +/- 58.8) and control (25.0 + 6.5) cats. Two nonketoacidotic cats also had high levels of D-lactate. There was a significant linear correlation (r = .684, P = .0001) between D-lactate and beta hydroxybutyrate concentrations. Serum D-lactate did not correlate with serum glucose (r = .078, P = .6825), and in vitro erythrocyte D-lactate formation did not increase in the presence of hyperglycemia. These data suggest that hepatic ketone metabolism, rather than hyperglycemia, may be a major source of serum D lactate in diabetics. PMID- 7885272 TI - Tissue-related changes in insulin receptor number and autophosphorylation induced by starvation and diabetes in rats. AB - Insulin action is subject to regulation at the level of the insulin receptor and at postreceptor levels. Starvation and diabetes are often associated with insulin resistance for glucose metabolism in various tissues. In muscle, fat, and liver, we examined whether changes in the functionality of the insulin receptor correlated with changes in insulin action in the starved and diabetic state. Insulin-stimulated receptor autophosphorylation reflects an early physiologic step in transmission of the insulin signal, and for that reason, changes in autophosphorylation activity of the insulin receptor were used as a marker to determine the functionality of the insulin receptor. Glycoprotein fractions prepared from skeletal muscle, diaphragm, epididymal fat, and liver of control, 3 day starved, short-term 3-day (S) diabetic (streptozotocin, 70 mg/kg intravenously), and long-term 6-month (L) diabetic (neonatal streptozotocin 100 micrograms/g intraperitoneally) rats were used in this study. Receptor activity was monitored by measuring insulin-stimulated [gamma-32P]adenosine triphosphate (ATP) receptor autophosphorylation. In addition, to obtain information about whether changes in receptor autophosphorylation are related to changes in receptor number, relative numbers of high-affinity insulin receptors were determined by affinity cross-linking of [125I]insulin to the receptor alpha-chain and quantitation of the yield of labeled receptor alpha-chain. Control, starved, S diabetic, and L diabetic rats had plasma insulin and glucose levels of 294 +/- 42, 90 +/- 24, 48 +/- 12, and 216 +/- 30 pmol/L and 6.7 +/- 0.2, 4.1 +/- 0.2, 23.3 +/- 0.7, and 21.6 +/- 2.9 mmol/L, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885273 TI - Effect of dexamethasone and prednisolone on insulin-induced activation of protein kinase C in rat adipocytes and soleus muscles. AB - We examined the effect of glucocorticoids on [3H]2-deoxyglucose ([3H]2-DOG) uptake, [125I]insulin binding, tyrosine kinase activity, and protein kinase C (PKC) activity in rat adipocytes and soleus muscles. In adipocytes, insulin stimulated [3H]2-DOG uptake was decreased by prior 60-minute treatment with dexamethasone (DEX) or prednisolone (PSL), whereas [125I]insulin binding, insulin (INS) receptor autophosphorylation, and tyrosine kinase activity, as measured using exogenous substrate of poly(Glu80-Tyr20), were not significantly changed. Cytosolic PKC activity decreased and membrane-associated PKC activity increased during a 60-minute treatment of adipocytes and soleus muscles with DEX or PSL, indicating that both DEX and PSL stimulate the translocation and activation of PKC. However, pretreatment of adipocytes and soleus muscles with glucocorticoids resulted in reduced INS-stimulated translocation of PKC from cytosol to membrane. INS-induced decreases in cytosolic PKC activity (50% +/- 7% v 10% +/- 8% and 20% +/- 7%, P < .05 to .01, for nonpretreated [control], DEX pretreated, and PSL pretreated cells) and increases in membrane PKC (100% +/- 10% v 50% +/- 9% and 20% +/- 9%, P < .01, for control, DEX pretreated, and PSL pretreated cells) were larger in nonpretreated adipocytes than in adipocytes pretreated with glucocorticoids. These results raise the possibility that glucocorticoids, namely, DEX and PSL, stimulate the translocation and subsequent degradative downregulation of PKC, and that this may be pertinent to their inhibitory effects on INS-stimulated glucose transport. PMID- 7885274 TI - Effects of an American Heart Association step I diet and weight loss on lipoprotein lipid levels in obese men with silent myocardial ischemia and reduced high-density lipoprotein cholesterol. AB - Reduced plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are a risk factor for coronary artery disease (CAD). In this study, we examined the sequential effects of an isocaloric American Heart Association (AHA) step I diet and a hypocaloric AHA step I diet (AHA step I diet + weight loss) on lipoprotein lipid levels in 14 middle-aged and older (60 +/- 6 years, mean +/- SD) obese (body mass index [BMI] > 27 kg/m2) nondiabetic men with exercise-induced silent myocardial ischemia (SI) and reduced HDL-C levels (0.85 +/- 0.14 mmol/L). Nine men of comparable age and obesity and with no evidence of exercise-induced ischemia that were evaluated longitudinally served as metabolic controls. In men with SI, after 3 months on the isocaloric AHA step I diet plasma triglyceride (TG) levels decreased by 26% (2.25 +/- 0.66 to 1.67 +/- 0.69 mmol/L, P < .005), cholesterol by 12% (5.24 +/- 0.84 to 4.62 +/- 0.78 mmol/L, P < .01), and low density lipoprotein cholesterol (LDL-C) by 10% (3.40 +/- 0.69 to 3.05 +/- 0.70 mmol/L, P < .01). However, plasma HDL-C levels also decreased by 7% (0.85 +/- 0.14 to 0.79 +/- 0.13 mmol/L, P < .05). Subsequent weight loss (11 +/- 4 kg) in conjunction with the AHA step I diet resulted in an additional decrease of 24% in TG (P < .005), 10% in cholesterol (P < .05), and 10% in LDL-C (P < .05). Plasma HDL-C levels increased by 8% (P < .01), thereby correcting the decline seen on the AHA step I diet alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885275 TI - Improvement of insulin sensitivity for glucose metabolism with the long-acting Ca channel blocker amlodipine in essential hypertensive subjects. AB - To clarify whether the long-acting calcium-channel blocker amlodipine restores insulin insensitivity in essential hypertension, insulin sensitivity tests were performed at the physiological steady-state insulin level (45 to 55 microU/mL) before and after amlodipine (2.5 to 7.5 mg/d) administration for 2 to 4 months in borderline and mild essential hypertensive subjects. Instead of somatostatin, Sandostatin (Sandoz, Basel, Switzerland) was used for the determination of steady state plasma glucose (SSPG) in the same way as previously described. SSPG, which was initially high (212.9 +/- 18.0 mg/dL, mean +/- SE), was significantly reduced to 169.8 +/- 14.7 after amlodipine treatment. Responses of ketone bodies during the test at 30 minutes, which reflect the insulin effect on lipolysis in adipose tissue and hepatic fatty acid oxidation, also improved after amlodipine treatment. Norepinephrine, noted to be mildly elevated after amlodipine treatment, decreased during the sensitivity test at 2 hours probably due to the sedative effect, without any change in the fractional extraction of Na. This indicates that the physiological level of insulin does not activate sympathetic nerve activity or stimulate Na reabsorption. The long-acting calcium-channel blocker amlodipine has significantly improved the initially decreased insulin sensitivity for glucose metabolism at least partially in borderline or mild essential hypertension. PMID- 7885276 TI - Age-related changes in pancreatic islet cell gene expression. AB - Previous studies have indicated that insulin secretion in response to glucose diminishes with age but insulin synthesis and gene transcription do not. To determine whether expression of genes other than those that encode insulin are subject to age-related changes that could alter pancreatic islet function, mRNAs for insulins I and II, amylin, glucose transporter 2 (GluT2), glucagon, and glucokinase were quantified in 2-, 6-, 12-, and 24-month-old Fischer 344 rats using species-specific ribonuclease (RNase) protection assays. There was only a modest (1.2- to 1.3-fold) increase in insulin I and insulin II mRNAs between ages 2 and 12 months. There were no statistically significant changes in levels of glucokinase mRNA with age. In contrast, the abundances of amylin, GluT2, and glucagon mRNAs all doubled during the same period. Variance in values from 24 month-old rats was too great to allow conclusions, except that the ratio of insulin II mRNA to insulin I mRNA increased with age. This change was not related to islet mass or total insulin mRNA abundance because it persisted at age 24 months, when total mRNA abundance had decreased. These results indicate that aging is associated with significant alterations in the relative proportion of expression of pancreatic islet cell genes implicated in insulin secretion and in intraislet glucose metabolism. PMID- 7885277 TI - Influence of stage of lactation on glucose and glutamine metabolism in isolated enterocytes from dairy cattle. AB - Pathways of glutamine and glucose metabolism in early-, mid-, and late-lactation dairy cows were evaluated by in vitro incubations of enterocytes for 2 hours with [U-14-C]glutamine and [U-14C]glucose. Enterocytes from early-lactation cows produced greater amounts of CO2 from glutamine in concentrations that ranged from 2 to 8 mmol/L than enterocytes from either mid- or late-lactation cows. Enterocytes from early-lactation cows also produced greater amounts of CO2 from 4 and 6 mmol/L glucose than enterocytes from either mid- or late-lactation cows. Glutamine was metabolized via glutaminolysis mainly to ammonia, alanine, aspartate, glutamate, and CO2, and more of these products were produced in enterocytes from early-lactation cows than from pooled mid- and late-lactation (PML) cows. Glucose was metabolized mainly to lactate, as compared with pyruvate and CO2. Lactate and CO2 production were both greater in enterocytes from early lactation cows than from PML cows. Glutamine as the sole substrate accounted for all the energy requirements of enterocytes from early-lactation cows but contributed only 31% in the presence of glucose. Similarly, glucose accounted for all the energy requirements of enterocytes from early-lactation cows and contributed 69% in the presence of glutamine. In enterocytes from all cows, the rate of adenosine triphosphate (ATP) production was greater in the presence of both glucose and glutamine compared with that in the presence of either substrate alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885278 TI - Concentration-dependent glucose-lowering effects of oral vanadyl are maintained following treatment withdrawal in streptozotocin-diabetic rats. AB - We have recently reported that treatment with vanadyl sulfate 0.75 mg/mL in drinking water eliminates hyperglycemia in a subset of streptozotocin (STZ) diabetic rats, with some rats remaining unresponsive to such treatment. In the present study, we demonstrate that unresponsive diabetic animals become normoglycemic when given higher concentrations of vanadyl. Since the subset of rats that require higher concentrations ([HC] 1.25 to 1.50 mg/mL) were found to be more severely diabetic before treatment than those that responded to lower concentrations ([LC] 0.75 to 1.00 mg/mL), the relative amount of residual circulating insulin (LC 36.0 +/- 2.2 v HC 25.6 +/- 3.3 microU/mL) appeared to be a key element in achievement of a normoglycemic effect to a given dose of vanadyl. Similarly, STZ-diabetic animals that responded to euglycemia with a more potent organic vanadyl compound (naglivan) had higher pretreatment plasma insulin levels than unresponsive animals (DT-R) (35.5 +/- 1.9 v 24.2 +/- 3.6 microU/mL). Vanadyl treatment over 10 weeks resulted in a period of normalized glucose levels and glucose tolerance after treatment was stopped. At 20 weeks after withdrawal from treatment with vanadyl sulfate, 13 of 19 animals remained euglycemic, whereas four of seven naglivan-treated animals also maintained normal glucose levels after a 30-week withdrawal period. At 3 weeks after withdrawal, maintenance of normal glucose homeostasis appeared to be independent of altered insulin levels, whereas at 20 weeks an improved insulin secretion, albeit 50% that of age-matched controls both in the fed state and in response to a glucose dose, was sufficient to return plasma glucose levels to the normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885279 TI - Training status, resting metabolic rate, and cardiovascular disease risk in middle-aged men. AB - We investigated differences in resting metabolic rate (RMR) and cardiovascular disease risk factors among 86 middle-aged men (36 to 59 years) classified as resistance-trained ([RT] n = 19), aerobic-trained ([AT] n = 37), or untrained ([UT], n = 30) according to habitual exercise patterns. RMR, body composition, body fat distribution, supine blood pressure, maximal aerobic capacity (VO2max), plasma lipid levels, and fasting levels of insulin, glucose, and thyroid hormones were measured. We found that RMR, adjusted for differences in fat-free mass, showed a tendency to be greater in AT men as compared with RT men (P = .09) and was greater in AT men as compared with UT men (P < .05). No differences in RMR were noted between RT and UT men. UT men had higher values for total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and the insulin to glucose ratio and lower values for high-density lipoprotein cholesterol (HDL-C) (all P < .01) as compared with RT and AT men, whereas no differences in these variables were noted between RT and AT men. Supine diastolic blood pressure was lower in RT men as compared with both AT and UT men. Stepwise regression analysis showed that variations in body fatness accounted for the greatest variation in fasting lipid profile, blood pressure, and the insulin to glucose ratio among groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885280 TI - Effect of insulin on SN-1,2-diacylglycerol species and de novo synthesis in rat skeletal muscle. AB - Insulin treatment increases the SN-1,2-diacylglycerol (DAG) concentration in skeletal muscle. Because DAG may participate in transmission or modulation of the insulin receptor signal, we examined the effect of insulin on total DAG and on different DAG species in isolated rat hemidiaphragms incubated with 5 mmol/L glucose. Five DAG species (16:0-18:1 omega 9, 16:0-18:1 omega 7, 18:0-18:1 omega 9, 18:0-18:2 omega 6, and 18:1-18:2) were identified and quantified. After a 5 minute incubation with 60 nmol/L insulin, neither total DAG nor a DAG species increased; exposure to insulin for 10 or 20 minutes increased the concentration of total DAG and of several DAG species. Insulin did not increase DAG in muscles incubated without glucose. Two sources for the insulin-mediated DAG increase were considered: phosphatidylcholine (PC) hydrolysis and de novo DAG synthesis from glucose. Concentrations of choline and phosphocholine in muscle were not increased after 10-minute incubations with insulin. However, insulin increased 14C incorporation from [U-14C]glucose into DAG, triacylglycerol (TAG), and total lipids approximately threefold. Okadaic acid (OKA), an inhibitor of phosphoprotein phosphatases 1 and 2A, increased muscle DAG content and synthesis from glucose, similar to the effect of insulin. Doses of OKA or insulin that increased DAG mass greatly exceeded those required for stimulation of glucose transport. The insulin-mediated, relatively slow increase in muscle DAG observed here likely reflects primarily de novo synthesis from glucose. This effect would be downstream of insulin stimulation of glucose transport. However, a possible insulin-mediated, rapid transient increase in muscle DAG content and PC hydrolysis cannot be ruled out by our studies. PMID- 7885281 TI - Exogenous insulin dose-dependently suppresses glucopenia-induced glucagon secretion from perfused rat pancreas. AB - To clarify the role of insulin in modulating the glucagon response to glucose concentration changes, we investigated the effects of exogenous insulin (10 mU/mL, 100 mU/mL, and 3.3 U/mL) on responses to high glucose (5.6-->16.7 mmol/L), low glucose (5.6-->1.4 mmol/L), and arginine (10 mmol/L) stimulation using the perfused rat pancreas. Although glucagon levels were slightly suppressed by all of the exogenous insulin concentrations tested for the initial few minutes at 5.6 mmol/L glucose, baseline levels were maintained thereafter. Glucagon responses to high or normal glucose concentrations were not altered, but glucopenia-induced glucagon secretion was significantly suppressed as compared with that of controls (0.77 +/- 0.14 ng/min [10 mU/mL, n = 5], 0.55 +/- 0.14 ng/min [100 mU/mL, n = 5], 0.27 +/- 0.13 ng/min [3.3 U/mL, n = 5] v 1.38 +/- 0.20 ng/min [controls, n = 9], P < 0.05, respectively). The first phase of the glucagon response to arginine was potentiated (2.03 +/- 0.24 v 1.17 +/- 0.22 ng/min, P < .05) by 10 mU/mL exogenous insulin. The second phase of the glucagon response to arginine was significantly suppressed in the presence of higher concentrations of exogenous insulin (1.16 +/ 0.23 ng/min [100 mU/mL], 0.96 +/- 0.08 ng/min [3.3 U/mL] v 1.57 +/- 0.17 ng/min, P < .05, respectively). These results suggest that glucagon secretion is modified by the combined suppressive effects of glucose and insulin, although it is mainly glucose that mediates glucagon secretion in the physiological glucose range. Glucopenia- or arginine-induced glucagon secretion is suppressed by insulin. PMID- 7885282 TI - Diabetes mellitus, hypertension, and cardiovascular disease: which role for oxidative stress? AB - Accelerated atherosclerotic vascular disease is the leading cause of mortality in patients with diabetes mellitus. Endothelium-derived nitric oxide (NO) is a potent endogenous nitrovasodilator and plays a major role in modulation of vascular tone. Selective impairment of endothelium-dependent relaxation has been demonstrated in aortas of both nondiabetic animals exposed to elevated concentrations of glucose in vitro and insulin-dependent diabetic animals. The impaired NO release in experimentally induced diabetes may be prevented by a number of antioxidants. It has been hypothesized that oxygen-derived free radicals (OFR) generated during both glucose autoxidation and formation of advanced glycosylation end products may interfere with NO action and attenuate its vasodilatory activity. The oxidative injury may also be increased in diabetes mellitus because of a weakened defense due to reduced endogenous antioxidants (vitamin E, reduced glutathione [GSH]). A defective endothelium-dependent vascular relaxation has been found in animal models of hypertension and in hypertensive patients. An imbalance due to reduced production of NO or increased production of free radicals, mainly superoxide anion, may facilitate the development of an arterial functional spasm. Treatment with different antioxidants increases blood flow in the forearm and decreases blood pressure and viscosity in normal humans; vitamin E inhibits nonenzymatic glycosylation, oxidative stress, and red blood cell microviscosity in diabetic patients. Long term randomized clinical trials of adequate size in secondary and primary prevention could support the free-radical hypothesis for diabetic diabetic vascular complications and the use of antioxidants to reduce the risk of coronary heart disease. PMID- 7885283 TI - Age- and menopause-associated variations in body composition and fat distribution in healthy women as measured by dual-energy X-ray absorptiometry. AB - To assess the variation with age and menopause, 407 healthy normal women aged 18 to 75 years had body composition and fat distribution measured by dual-energy x ray absorptiometry (DEXA). The mean +/- SD are given for different age decades. Postmenopausal women had significantly more fat, a more central fat distribution, and less lean tissue mass (LTM) than premenopausal women. In premenopausal and postmenopausal women, age only correlated with the abdominal to total-body fat tissue ratio (r approximately .24, P < .05), whereas the years since onset of menopause correlated with fat tissue mass (FTM), fat%, abdominal fat%, and the abdominal to total-body fat tissue ratio (r approximately .2, P < .05). To assess the independent impact of age, menopausal status, and years since menopause, multiple linear regressions were performed. FTM, fat%, and abdominal fat% were significantly related to menopausal status and years since menopause independently of age. The abdominal to total-body fat tissue ratio was statistically significantly related to age, but tended also to be independently related to years since menopause. LTM was statistically significantly related to menopausal status independently of age and years since menopause. In summary, we suggest that in healthy women total-body and abdominal fat may increase and LTM may decrease in the years after menopause, primarily in the perimenopausal years, without significant changes before menopause. PMID- 7885284 TI - Monocytes from patients with combined hypercholesterolemia-hypertriglyceridemia and isolated hypercholesterolemia show an increased adhesion to endothelial cells in vitro: II. Influence of intrinsic and extrinsic factors on monocyte binding. AB - One of the primary risk factors for atherosclerosis is hypercholesterolemia. Patients with isolated hypercholesterolemia or combined hypercholesterolemia hypertriglyceridemia are at risk to develop premature atherosclerosis. Diet induced hypercholesterolemia in animals leads to an increased adhesion of monocytes to and transmigration through the intact endothelium of the vessel wall. In the present study, we investigated in vitro binding of freshly isolated monocytes from patients and healthy controls to a monolayer of endothelial cells obtained from human umbilical vein. All four diagnosed patient groups with isolated or combined hypercholesterolemia showed a significant increase in monocyte binding as compared with the control group (familial hypercholesterolemia [FH], +41%; polygenic hypercholesterolemia [PH] +35%; familial combined hypercholesterolemia [FCH], +47%; nonfamilial combined hypercholesterolemia-hypertriglyceridemia [CHH], +67%). In a longitudinal study it was observed that diet or medication induced a decrease in cholesterol and triglycerides; however, these therapeutic conditions did not diminish in vitro monocyte binding in the patient groups. There was no correlation between monocyte binding and plasma cholesterol, low-density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, or lipoprotein(a) within hyperlipidemic patient groups. The presence of heart and vessel disease in hyperlipidemic patients was not associated with a change in monocyte binding. The adhesion to endothelial cells of monocytes from smoking patients with combined hypercholesterolemia (27%) was significantly higher (+23%) than that of monocytes from nonsmoking patients. Cytofluorimetric analysis of monocytes from FCH and CHH patients for specific monocyte differentiation markers and integrins did not show differences as compared with monocytes from healthy controls. PMID- 7885285 TI - Effect of glucocorticoids on the paradoxical growth hormone response to thyrotropin-releasing hormone in patients with acromegaly. AB - It has been hypothesized that in acromegalic patients, as well as in normal subjects, acute increases in serum cortisol levels may cause an enhancement of hypothalamic somatostatin secretion, which in turn may be responsible for the glucocorticoid-mediated growth hormone (GH) inhibition. The aim of this study was to investigate short-term effects of an intravenous (i.v.) infusion of hydrocortisone on the GH response to thyrotropin-releasing hormone (TRH) in acromegaly. We studied six adult patients with active acromegaly. The group was composed of four women and two men with a mean age of 55.8 +/- 6.4 years (range, 27 to 68) and a mean body mass index of 26.7 +/- 1 kg/m2 (range, 23.3 to 30). All patients underwent the following treatments: (1) hydrocortisone alone: a bolus i.v. injection of hydrocortisone succinate 100 mg in 2 mL saline at time -60 minutes, followed by a 120-minute i.v. infusion of hydrocortisone succinate 250 mg in 250 mL saline from -60 to 60 minutes; (2) TRH+hydrocortisone: a bolus i.v. injection of TRH 200 micrograms 60 minutes after initiation of a 2-hour hydrocortisone infusion; (3) TRH alone: a bolus i.v. injection of TRH at time 0, 60 minutes after initiation of a 2-hour saline infusion. In all six patients, TRH induced large GH increases (absolute peak GH level, 58.1 +/- 23.2 micrograms/L; maximum % GH change with respect to baseline, 1,397.8% +/- 807.8%; range, 205% +/ 5,219%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885287 TI - Influence of 12 weeks of training by brisk walking on postprandial lipemia and insulinemia in sedentary middle-aged women. AB - The purpose of this study was to examine the influence of brisk walking on postprandial lipemia in 26 sedentary women aged 41 to 55 years. The lipemic response to a high-fat meal (mean +/- SEM: 73.8 +/- 1.3 g fat, 66% energy; 81.8 +/- 1.4 g carbohydrate) was determined pretraining and posttraining. Blood samples were obtained in the fasted state and hourly for 6 hours after the meal. Serum was analyzed for triacylglycerol (TAG), total cholesterol, high-density lipoprotein (HDL) and HDL2 cholesterol, apolipoproteins (apos) A-I and B, nonesterified fatty acids (NEFA), glucose, and insulin. Subjects were randomly assigned to one of two groups: walkers (n = 13) followed a program of brisk walking (average of 21 +/- 1 [range, 17 to 27] min.d-1 at 1.76 +/- 0.02 m.s-1), whereas controls (n = 13) maintained their habitual life-style. Procedures were repeated 12 weeks later, with 48 hours between the last training session and determination of postprandial lipemia. Eleven walkers and 13 controls completed the study. Responses over time were compared between groups (Mann-Whitney U, P < .05). Brisk walking improved endurance fitness and decreased body fatness, but had no influence on peak TAG concentration (walkers, 1.6 +/- 0.2 v 1.6 +/- 0.2 mmol.L-1; controls, 1.9 +/- 0.3 v 2.1 +/- 0.3) or the area under the TAG/time curve after the test meal. The area under the insulin/time curve decreased in walkers relative to controls. These results suggest that in sedentary women aged 41 to 55, brisk walking attenuates the serum insulin response, but not the lipemic response, to consumption of a high-fat mixed meal when these responses are determined 48 hours after the last exercise bout. PMID- 7885286 TI - Insulin sensitization in diabetic rat liver by an antihyperglycemic agent. AB - This study aimed to demonstrate directly that the thiazolidinedione pioglitazone acts as an insulin sensitizer. We tested the hypothesis that pioglitazone treatment of diabetic rats alters liver function such that responsiveness of selected genes to subsequent insulin regulation is enhanced. Although flux through gluconeogenic/glycolytic pathways involves regulation of many enzymes, we presently report the effects of insulin on expression of two key enzymes in these metabolic pathways, ie, phosphoenolpyruvate carboxykinase (PEPCK) and glucokinase (GK). Rats were either studied as nondiabetic controls or injected with streptozotocin as a model for insulin-deficient diabetes. Diabetic animals were treated without or with pioglitazone and subsequently examined for acute responses to insulin. Pioglitazone treatment of diabetic animals significantly enhanced the effects of insulin to reverse elevated blood glucose. Although the mean level of liver mRNA transcripts encoding PEPCK was increased to nearly 300% in diabetic animals as compared with nondiabetic controls (100%), it was significantly lower in pioglitazone-treated diabetic rats (119% of control) than in diabetic rats without pioglitazone (223% of control) after insulin treatment. By contrast, mRNA transcripts encoding GK were not detectable in diabetic animals, but were increased markedly by insulin treatment in all animal groups. Insulin-enhanced expression of GK was significantly greater in liver from animals that were treated earlier with pioglitazone (291% of control) than in liver from those that were untreated (214% of control). An amplified acute response of liver to insulin thus established pioglitazone as an insulin sensitizer. Our findings further showed that such sensitization can be developed even in the insulin deficient state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885288 TI - Serum retinol levels throughout 2 years of cholesterol-lowering therapy. AB - Some studies have reported an inverse correlation between serum cholesterol level and risk of cancer. This correlation might be due to a decrease in serum retinol, a lipid-soluble vitamin that controls cell proliferation and differentiation. We evaluated the influence of cholesterol-lowering therapy on serum retinol in 102 subjects (mean +/- SE: aged 47.1 +/- 4.1 years; body mass index, 23.8 +/- 0.6 kg/m2) with primary hypercholesterolemia treated for 2 years with different therapeutic protocols. Twenty-two subjects had been treated with diet alone, 35 with diet and fibrates, 37 with diet and hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase inhibitors (statins), and eight with diet and cholestyramine. Postabsorptive serum retinol, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL C), and triglyceride levels were determined at baseline and every 3 months. Baseline TC and LDL-C were significantly lower in the diet-treated group than in other groups. No intergroup differences were found in pretreatment levels of triglycerides and serum retinol. After 2 years of treatment, TC and LDL-C serum levels were not significantly decreased in the diet-alone group, whereas they were decreased by 20% and 24%, respectively, in the gemfibrozil group, 28% and 34% in the statins group; and 21% and 27% in the cholestyramine group. In the entire population (N = 102), serum retinol was 3.46 +/- 0.08 mumol/L before therapy and 3.76 +/- 0.07 after 2 years of therapy (P < .001). Serum retinol increased in diet- and statin-treated groups, but not in fibrate- and resin treated groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885289 TI - Cardiac natriuretic peptides inhibit cyclosporine-induced production of endothelin in cultured rat mesangial cells. AB - Cyclosporine A (CSA) stimulates vascular endothelial cell production of endothelin-1 (ET-1). The present study was designed to test two hypotheses: (1) CSA stimulates ET-1 secretion in cultured rat mesangial cells, and (2) cardiac natriuretic peptides, atrial and brain natriuretic peptides (ANP and BNP), inhibit the above-mentioned secretion in these cells. CSA stimulated ET-1 secretion in a concentration-dependent manner between 10 and 100 ng/mL. In contrast, high concentrations of CSA (10 and 100 micrograms/mL) were cytotoxic and failed to stimulate ET-1 secretion. Rat ANP (1-28) and rat BNP-45 exhibited clearly concentration-related inhibition of CSA-induced ET-1 secretion. This inhibition by ANP and BNP was paralleed by an increase in the cellular level of cyclic guanosine-3',5'-monophosphate (cGMP). Rat ANP (5-25) was less effective than rat ANP (1-28) with respect to inhibiting ET-1 secretion and increasing cellular cGMP. Addition of a cGMP analog, 8-bromo-cGMP, reduced CSA-induced ET-1 secretion. On the other hand, addition of a cyclic adenosine-3',5'-monophosphate (cAMP) analog, 8-bromo-cAMP, did not affect CSA-induced ET-1 secretion. These findings suggest that CSA in low concentrations stimulates ET-1 production in cultured rat mesangial cells, and that cardiac natriuretic peptides inhibit this stimulated production, probably through a cGMP-dependent process. PMID- 7885290 TI - Effects of continuous low-dosage hormonal replacement therapy on lipoprotein metabolism in postmenopausal women. AB - The effects on lipoprotein metabolism of female hormone replacement therapy (HRT) for 7 weeks with combined low dosages of a widely used oral progestin and estrogen combination, medroxyprogesterone acetate ([MPA] 2.5 mg/d) and conjugated equine estrogen ([CEE] 0.625 mg/d), were studied in six postmenopausal women. To investigate the mechanism of the reduction of low-density lipoprotein (LDL) cholesterol by HRT, the kinetics of very-low-density lipoprotein (VLDL) and LDL apolipoprotein (apo) B turnover were studied by injection of autologous 131I labeled VLDL and 125I-labeled under control conditions and again in the fourth week of HRT. HRT induced (1) a 12% +/- 4% (P < .02) reduction of the cholesterol content of LDL of Sf 0-12, which was attributable to a 15% +/- 5% decrease in the mean ratio of cholesterol to apo B (1.3 +/- 0.1 v 1.5 +/- 0.1, P < .025), and (2) a 13% +/- 4% increase in the mean fractional catabolic rate (FCR) of LDL apo B (0.34 +/- 0.03 v 0.30 +/- 0.02 pools/d, respectively, P +/- .05). However, there were no significant changes in mean values for (1) pool size (42 +/- 4 v 43 +/- 3 mg/kg) or production rate (14 +/- 0.5 v 13 +/- 0.9 mg/kg/d, P > .1) of LDL apo B or (2) pool size (2.5 +/- 0.6 v 2.8 +/- 0.6 mg/kg), FCR (8.0 +/- 2.0 v 8.1 +/- 1.7 pools/d) or production rate (16 +/- 4 v 19 +/- 2 mg/kg/d, P > .4) [corrected] of VLDL apo B. HRT increased high-density lipoprotein (HDL) cholesterol concentration significantly (by 16% to 18%, P < .05), whereas the mean ratio of plasma total cholesterol to HDL cholesterol decreased by 19% +/- 3% (P < .005). HRT favorably influenced the overall plasma lipoprotein lipid vascular risk profile while significantly altering both the composition and fractional catabolism of LDL. PMID- 7885291 TI - [Dosimetry of DNA and protein adducts in occupational health]. AB - Genotoxic carcinogenic compounds react chemically with DNA and proteins to form covalent adducts which, in the case of DNA adducts, are strongly believed to be the first step in cancer process (biologically effective dose). The paper reviews the main studies on the dosimetry of adducts in the biological monitoring of occupational exposure to mutagens and carcinogens. Dosimetry of DNA adducts has been used to assess exposure to polycyclic aromatic hydrocarbons in environments such as foundries, coke ovens and the aluminium industry. In many cases, adduct levels higher than those of control populations were found in exposed workers. Only one study reported increased levels of DNA adducts in workers exposed to styrene. Dosimetry of hemoglobin adducts has been used to identify occupational exposure to ethylene oxide, styrene, BaP and arylamines. The results obtained in the last few years confirm the usefulness of dosimetry of DNA and protein adducts in assessing occupational exposure to genotoxic carcinogens occurring in working environments, even at very low exposure levels, but the methods in question require high standardization and validation if systematic errors in measurement are to be avoided. In the coming years, dosimetry of adducts, together with evaluation of individual genetic sensitivity to mutagens and carcinogens, will be one of the new frontiers in research on the prevention of occupational cancer. Current research already makes use of sophisticated analytical techniques such as mass spectrometry, and both specificity and sensitivity in the determination of adducts have been considerably improved. In the future, therefore, dosimetry of adducts may also be applied to industrial health practices. PMID- 7885292 TI - Blood and urine concentrations of chemical pollutants in the general population. AB - The concentration of 9 environmental chemical pollutants in the general population was measured in blood and urine. For the 9 different pollutants, the blood samples tested varied from 88 for acetone to 431 for benzene. Urine samples varied from 48 for styrene to 213 for n-hexane. Six of these agents (benzene, toluene, styrene, n-hexane, acetone and carbon disulphide) were present in all or almost all (100-94%) blood samples. The three chlorides (chloroform, trichloroethylene and tetrachloroethylene) were present only in 60-85% of samples. After acetone, with blood concentrations in microgram/1 (mean 840 microgram/l), the highest mean blood levels were those of toluene (1097 ng/l), chloroform (955 ng/l) and n-hexane (642 ng/l). Trichloroethylene and free carbon disulphide showed similar values (458 and 438 ng/l, respectively). Finally, benzene, styrene and tetrachloroethylene showed the lowest values (262, 217 and 149 ng/l, respectively). There was generally a significant difference between rural and urban workers in terms of blood benzene (200 ng/l vs 264 ng/l), trichloroethylene (180 ng/l vs 763 ng/l) and tetrachloroethylene (62 ng/l vs 263 ng/l). In a group of subjects potentially exposed to industrial solvents, classed as chemical workers, blood benzene, toluene, chloroform and n-hexane were significantly higher than in rural and urban workers. Smokers showed a significantly higher blood concentration than non-smokers for benzene (381 ng/l vs 205 ng/1), toluene (1431 ng/l vs 977 ng/l), and n-hexane (838 ng/l vs 532 ng/l). All or almost all urine samples (100-92%) contained all the compounds except trichloroethylene and tetrachloroethylene, present in 79% and 76% of samples, respectively (table 2). Urinary concentrations of all compounds did not differ significantly between rural and urban workers. Benzene and toluene were significantly higher in in urine of smokers than of non-smokers. Chloroform and n hexane showed significantly higher urinary than blood values. Excluding acetone, with urinary and blood concentrations in pg/l, chloroform, toluene and n-hexane showed the highest mean concentrations both in blood and in urine. PMID- 7885293 TI - [Epidemiological study of mortality in a cohort of rayon industry employees]. AB - A cohort of 166 employees in the SNIA viscosa rayon production plant in Padua was followed up for mortality up to 1989. The study detected a statistically significant increase in total mortality mainly due to an excess of deaths from ischaemic heart diseases (ICD 410-414). Workers affected by occupational disease in the age group 50-64 years had the highest risk with a threefold increase in mortality compared to the general population. An increasing pattern of lung cancer mortality with time since first exposure was observed. The SMR for lung cancer was 192 for smokers with occupational disease. PMID- 7885294 TI - Mortality among workers of three thermoelectric power plants in northern Italy: a retrospective cohort study. AB - During the last ten years, interest has been focussed on occupational exposure in thermoelectric power plants (i.e., coal dust, polycyclic aromatic hydrocarbons, dioxin, dielectric liquids, PCB's, asbestos, etc.), although available evidence on its effects on the health status of the occupational population are far from being definitive. A retrospective cohort study was carried out to investigate the association between exposure to risk factors and mortality for cancer in three thermoelectric power plants located in the north-east of Italy. The three plants studied started with oil and coal but since 1968 they utilized mostly coal as fuel. In spite of the different fuel used at the beginning, the production process has been fairly constant since the main conversion from oil to coal with a substantial increase in power production. A total of 1,772 male workers were included in the total study cohort and followed-up from 1968 to 1987, with a total of 22,090 person-years of exposure. Eighty percent of the cohort began to work in the plant before 30 years of age, and had a mean period of employment of 9.5 years. The cohort was completely traced to the end of the follow-up period by using an original computer system based on personal fiscal codes. Causes of death were ascertained in the municipalities where the deaths occurred and coded according to the International Classification of Disease, IX Revision. During the study period 68 deaths were observed with an SMR for all causes of death equal to 0.79.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885295 TI - Storage mites and their role in the onset of asthma and oculorhinitis among cattle farmers in north-east Italy. AB - The results are reported of an epidemiological study carried out in the province of Treviso in north-east Italy. The research was designed to ascertain the sensitization, through an IgE mechanism, to the main allergens present on cattle farms. Also reported are the results of a mite survey undertaken in ten barns in the same region. Investigations revealed a significantly larger degree of sensitization to storage mites among cattle farmers than in the control subjects. This sensitization was well correlated with mite species to be found in cattle barns. However, the frequent co-sensitization to Dermatophagoides offers a topic for further study. PMID- 7885296 TI - [Exposure to benzene of service station employees and composition of benzene]. AB - The International Agency for Research on Cancer (IARC) classifies gasoline vapours and exhaust fumes from gasoline fueled automobiles as potential human carcinogens. Data on the chemical composition of gasoline marketed in Italy and especially on the concentration of benzene, are rather poor. Within the framework of an investigation aimed at assessing the mean annual level of exposure to aromatic hydrocarbons among gasoline pump attendants, made on a sample of attendants in Rome between December 1991 and November 1992, samples of gasoline were also collected so as to determine the benzene content of the gasoline over the investigation period, assess the variability of benzene concentration in the various gasolines and according to the season of the year, and take account of gasoline composition in analysing the factors determining individual exposure levels of pump attendants. Benzene exposure was measured via gas chromatography of air samples obtained with personal pumps in the breathing zone. The mean benzene exposure level (8 h TWA) of the 27 subjects under study was 1.73 mg/m3 (SD = 5.53). The benzene concentration in the samples of gasoline, which were collected on the same day as personal exposure monitoring was performed, was measured by means of high resolution gas chromatography (hr-GC). Mean benzene levels of 25.03 g/l (SD = 3.47), equivalent to 2.86% by volume, were measured in 24 samples of alkylated gasoline, and mean levels of 23.18 g/l (SD = 3.93), equivalent to 2.65% v/v, were measured in 10 samples of lead-free gasoline. Statistically significant associations were found between individual exposure to benzene and the quantity of gasoline pumped (r = 0.69) and the quantity of benzene present in the gasoline sold on the day monitoring was performed (r = 0.70). Using regression analysis, the estimated increase in the level of personal benzene exposure was 0.01 mg/m3 for every increase of 100 g in the benzene content of the total amount of gasoline sold. This estimation could be used to quantify the expected reduction in benzene exposure levels in service station attendants following a reduction in the benzene content of gasoline. PMID- 7885297 TI - [Course on industrial medicine in graduate education of medicine and surgery at the University of Modena. Critical analysis of the judgment of students of the academic year 1993-1994]. AB - Assessment of teaching activity based on the judgment of students can provide useful information which can be used to revise and improve the courses. In the academic year 1993-1994 the course of "Occupational Medicine" was assessed in the Medical School of the University of Modena. Fifty-six out of 62 medical students participated in the study. An anonymous questionnaire was administered to obtain information on usefulness, clarity (presentation and visual aids quality), cultural and professional interest. Each student was requested to assess these aspects on a 5-point scale ranging from 1 (poor) to 5 (very good). The results show that some lectures ("Occupational History", "Allergic respiratory diseases") were considered more useful and more interesting from a professional point of view. No difference was found among the lectures with respect to clarity, which was considered as "good". Clarity depends mostly on the quality of the visual aids. The students suggested that 80% of the program should be covered during the course. PMID- 7885298 TI - [From COPD, COAD, CURS, CUSLK, CAO to CHAOS]. PMID- 7885299 TI - [Effect of the degree of revascularization on left ventricular function after aortocoronary bypass operation]. AB - BACKGROUND: The extent of myocardial revascularisation by aortocoronary bypass surgery can only be quantitatively evaluated by using precise criteria. In this retrospective study the effect of coronary surgery on left ventricular function was analyzed. PATIENTS AND METHODS: In 161 patients, 148 male and 13 female, aged 52.5 +/- 7.0 years (33 to 69 years) with 1 (7%), 2 (38%) or 3 vessel disease (55%) the left ventricular function was analyzed by Swan-Ganz catheterization at rest and on exercise, five months before and after coronary bypass operation. Coronary artery and bypass lesions were quantified according to a new detailed score including diseased main or side branches, segment 1 to 3, type of irrigation and area reduction of the artery cross-section. Pulmonary capillary wedge pressure and cardiac index were measured and related to the grade of revascularisation (RG) and pre-operative ejection fraction (EF), classified in the groups RG1 < 50%, n = 54; RG2 50 to 74%, n = 52; RG3 > or = 75%, n = 55, EF1 < 60%, n = 30 and EF2 > or = 60%, n = 129. RESULTS: The change in pulmonary capillary wedge pressure on exercise was in RG1, RG2 and RG3 -26.2%, -29.0% and 40.9%, respectively (p < 0.001). It was significantly higher in RG2 and RG3 than in RG1. The increase in cardiac index on exercise was significant only in groups RG2, RG3 and EF2 (p < 0.005). CONCLUSION: Adequate improvement of left ventricular function can be expected when a grade of revascularisation of 50% and more is achieved. PMID- 7885300 TI - [Results of the 75selenium homotaurocholic acid retention test (SeHCAT test) in diagnosis of diarrhea]. AB - PATIENTS AND METHOD: For that reason absorption of bile acids was investigated using the 75Se-homotaurocholate (SeHCAT) in 239 patients with diarrhoea. SeHCAT retention time was measured as 7 day retention time in a whole body counter. An intact bile acid absorption (negative SeHCAT test) was confirmed in 23 healthy volunteers within the range of 11 to 50% (mean +/- double standard deviation). RESULTS: In 135 patients with a possible type I bile salt malabsorption the SeHCAT test was positive in 78%, thus indicating bile salt malabsorption. The test is very sensitive detecting bile salt malabsorption in Crohn's disease, identifying ileal disease more precisely than radiology. The SeHCAT test ascertained type II primary bile salt malabsorption in 7 patients, as well as type III bile salt malabsorption in patients (9 out of 28) with cholecystectomy, vagotomy, partial gastrectomy and chronic pancreatitis. In addition, a positive SeHCAT test indicating bile acid malabsorption was found in 5 out of 11 patients with irritable syndrome, diarrhoeic form, and in 4 out of 12 patients with lactose intolerance. CONCLUSION: SeHCAT retention should be measured routinely in patients with chronic diarrhoea for which the cause is not obvious. PMID- 7885301 TI - [Recommendations of the German Respiratory League for treatment of patients with chronic obstructive bronchitis and pulmonary emphysema]. PMID- 7885302 TI - [Therapy of acute pancreatitis]. PMID- 7885303 TI - [The 75SeHCAT retention test--methodology and clinical applications]. PMID- 7885304 TI - [Malnutrition and nutrition in patients with cystic fibrosis]. PMID- 7885305 TI - [Interpretation of clinical studies]. PMID- 7885306 TI - [Osteoplastic skeletal changes in systemic mastocytosis]. PMID- 7885307 TI - [Diagnosis of dysfunctions of replanted parathyroid gland tissue by bilateral analysis of intact parathyroid hormones in cubital vein blood. A prospective study]. AB - AIM: In a prospective long-term follow-up study after operative therapy of hyperparathyroidism the value of bilateral determination of parathyroid hormone levels in cubital venous blood after total parathyroidectomy/autologous parathyroid gland reimplantation (musculus brachioradialis) for diagnosis of dysfunctioning grafted tissue is evaluated. PATIENTS AND MATERIAL: From August, 1, 1987 to March, 31, 1994 68 of 243 patients operated on for hyperparathyroidism underwent total parathyroidectomy. Autologous reimplantation of parathyroid gland was carried out simultaneously in 64 patients. Twice delayed reimplantation of cryopreserved tissue was carried out, and there was no reimplantation in two patients up to this day. Three patients were operated on for hyperfunctioning parathyroid autograft after former total parathyroidectomy/reimplantation. RESULTS: During follow-up 5 patients developed dysfunction of (reimplanted) parathyroid gland. Because of low or unprovable levels of intact parathormone the gradients of intact parathyroid hormone between grafted and nongrafted forearm were about 1:1 in postoperative hypoparathyroidism as well as in hypofunction of parathyroid gland. After successful replantation of cryopreserved parathyroid tissue gradients of intact parathyroid hormone increased (> 1:10). In hyperfunction of grafted parathyroid tissue hormone gradients were high (> 1:20 to 1:45,3) because of excessive high levels of intact parathormone in the cubital vein of the graft bearing arm. Successful reduction of parathyroid graft was followed by decrease of parathyroid hormone gradients. CONCLUSION: Regular follow up of intact parathormone gradients together with intact parathyroid hormone levels and serumcalcium analysis allow the determination of parathyroid graft function. Also differentiation between graft dependent hyperparathyroidism and hyperfunctioning parathyroid tissue in the neck or mediastinum seems to be possible by bilateral determination of intact parathormone. Normal values or a normal range for intact parathyroid hormone gradients can not yet be defined. PMID- 7885308 TI - Anticholinergic poisoning associated with an herbal tea--New York City, 1994. AB - Inadvertent anticholinergic poisoning can result from consumption of foods contaminated with plants that contain belladonna alkaloids. During March 1994, the New York City Department of Health (NYCDOH) investigated seven cases of anticholinergic poisoning in members of three families; three of the seven ill persons required emergency treatment for characteristic manifestations. For all cases, manifestations occurred within 2 hours after drinking tea made from leaves purchased commercially and labeled as Paraguay tea--an herbal tea derived from the plant llex paraguariensis, which is native to South America. This report summarizes the investigation of these cases. PMID- 7885309 TI - Health-related quality-of-life measures--United States, 1993. AB - Measures of health-related quality of life (HR-QOL) are used to evaluate the outcomes of interventions and the need for health services (1,2). HR-QOL includes how persons perceive their own health--which reliably predicts loss of function, morbidity, and mortality (3-5)--and how well they function physically, psychologically, and socially during usual daily activities. Measures of HR-QOL are important because they assess dysfunction and disability not reflected by standard measures of morbidity and mortality. Since January 1993, the Behavioral Risk Factor Surveillance System (BRFSS) has included four HR-QOL questions regarding overall self-rated health and recent physical health, mental health, and activity limitation (6). This report describes 1993 BRFSS results for state specific differences in these measures of HR-QOL. PMID- 7885310 TI - Foodborne botulism--Oklahoma, 1994. AB - On July 2, 1994, the Arkansas Department of Health and the Oklahoma State Department of Health were notified about a possible case of foodborne botulism. This report summarizes the investigation, which implicated consumption of improperly stored beef stew. PMID- 7885311 TI - Notification of syringe-sharing and sex partners of HIV-infected persons- Pennsylvania, 1993-1994. AB - In April 1993, a man incarcerated in a prison in Berks County in eastern Pennsylvania voluntarily requested testing for human immunodeficiency virus (HIV) antibody and was diagnosed with HIV infection. Following an interview and counseling by Pennsylvania Department of Health HIV Prevention Program (HIVPP) staff (1), he provided contact information about four persons with whom he had shared syringes to inject drugs before incarceration. As a result of follow-up investigation, HIV infection was diagnosed in two of these four persons. One of these two persons provided contact information about 47 partners, including 41 partners with whom he had shared syringes only and six with whom he had had sex and shared syringes. By May 1994, partner notification follow-up of the four partners of the index patient and all subsequently identified partners of HIV infected persons identified a social network of 124 persons linked by syringe sharing and/or sex. This report describes the findings of the investigation of this network during April 1993-May 1994 and limited additional information from June-September 1994. PMID- 7885312 TI - Self-treatment with herbal and other plant-derived remedies--rural Mississippi, 1993. AB - Herbal and other plant-derived remedies have been estimated by the World Health Organization (WHO) to be the most frequently used therapies worldwide. Therapeutic agents derived from plants include pure chemical entities available as prescription drugs (e.g., digitoxin, morphine, and taxol), standardized extracts, herbal teas, and food plants; plant-derived remedies can contain chemicals with potent pharmacologic and toxicologic properties. Although precise levels of use of these remedies in the United States are unknown, in 1991, herbal products accounted for sales of approximately $1 billion. Previous reports about herbal remedies in the rural South have described the use and biologic activities of locally gathered plant species and details of preparation and dosage, but have not determined the prevalence of use of plant-derived remedies in the study population and the prevalence of use of specific remedies. To assess the prevalence of use of plant-derived remedies (excluding prescription drugs) and the prevalence of use of specific remedies in rural central Mississippi, The University of Mississippi conducted a survey during March-June 1993. This report describes two case reports of use of these remedies and summarizes the findings of the survey. PMID- 7885313 TI - Emergence of penicillin-resistant Streptococcus pneumoniae--southern Ontario, Canada, 1993-1994. AB - Streptococcus pneumoniae is a leading cause of infectious disease-related illness and death in the United States, accounting for an estimated 3000 cases of meningitis, 50,000 cases of bacteremia, 50,000 cases of pneumonia, and 7 million cases of acute otitis media each year. Penicillin has been the antibiotic of choice for the treatment of infections caused by S. pneumoniae; since the mid 1980s, the prevalence of penicillin-resistant S. pneumoniae has increased substantially worldwide. In Canada, a strain of pneumococcus with reduced susceptibility to penicillin was first reported in 1974; based on surveys during 1977-1990, rates of resistance to penicillin were 2.4%, 1.5%, and 1.3% in the provinces of Alberta, Ontario, and Quebec, respectively. To determine whether the prevalence of penicillin resistance had increased among pneumococcal isolates, investigators from the University of Toronto tested the susceptibility of strains collected from a Toronto hospital and from a surrounding region in southern Ontario during June-December 1993 and March-June 1994. This report summarizes the results of this investigation. PMID- 7885314 TI - Health insurance coverage and receipt of preventive health services--United States, 1993. AB - In 1992, an estimated 38.5 million U.S. residents aged < 65 years did not have health insurance (1). Efforts by states to expand health-care coverage will require surveillance for and state-specific information about coverage for acute care and the receipt of preventive services. This report summarizes state specific and aggregated data from the 1993 Behavioral Risk Factor Surveillance System (BRFSS) regarding the status of health insurance coverage and the receipt of preventive health services among adults aged 18-64 years. In addition, findings from the analysis of supplemental questions added to the BRFSS in Minnesota are included that address health-care utilization, source of health care coverage, and coverage of children. PMID- 7885315 TI - Evaluation of congenital syphilis surveillance system--New Jersey, 1993. AB - To monitor disease burden and trends associated with congenital syphilis (CS), effective prevention programs require a surveillance system that identifies CS cases in an accurate and timely manner. Before 1988, comprehensive CS surveillance was difficult for health departments to conduct because documentation of infection in infants required complex and costly long-term follow-up for up to 1 year after delivery; follow-up often was incomplete, and many infected infants were not identified. To estimate the public health burden of CS more accurately and eliminate long-term follow-up of infants by health department personnel, in 1988 CDC implemented a new CS case definition (1). Rather than relying on documentation of infection in the infant, the new case definition presumes that an infant is infected if it cannot be proven that an infected mother was adequately treated for syphilis before or during pregnancy (2). During 1993-1994, the Sexually Transmitted Disease Prevention and Control Program of the New Jersey Department of Health (NJDOH) evaluated its CS surveillance system to assess the accuracy and completeness of reporting using the new case definition and to determine the personnel costs associated with identifying and classifying CS cases. This report summarizes the results of the evaluation. PMID- 7885316 TI - Co-incidence of HIV/AIDS and tuberculosis--Chicago, 1982-1993. AB - In 1985, the epidemic of human immunodeficiency virus (HIV) infection was recognized as an influence on the increasing occurrence of tuberculosis (TB) in the United States (1). Programs to control and prevent TB require information characterizing the interaction between HIV infection and TB, particularly in locally defined populations. This report describes the overall occurrence of TB in Chicago (1990 population: 2,783,726) during 1982-1993 and characterizes the co incidence of TB and HIV/acquired immunodeficiency syndrome (AIDS) in Chicago during 1989-1993. PMID- 7885318 TI - World Health Day--April 7, 1995. PMID- 7885317 TI - NIOSH alert: request for assistance in preventing injuries and deaths of fire fighters. AB - CDC's National Institute for Occupational Safety and Health (NIOSH) periodically issues alerts on workplace hazards that have caused death, serious injury, or illness to workers. One such alert, Request for Assistance in Preventing Injuries and Deaths of Fire Fighters (1) was recently published and is available to the public. PMID- 7885319 TI - Mass vaccination with oral poliovirus vaccine--Asia and Europe, 1995. AB - The theme of World Health Day, April 7, 1995, is "Target 2000--A World Without Polio" (1). In conjunction with World Health Day activities, 18 geographically contiguous countries in Europe, Central and South Asia, and the Middle East are conducting coordinated National Immunization Days (NIDs)* with oral poliovirus vaccine (OPV) (Figure 1). The World Health Organization (WHO) has designated this effort "Operation MECACAR" (MEditerranean, CAucasus, and Central Asian Republics). This report describes the efforts of this campaign and summarizes polio surveillance data for 1994. PMID- 7885320 TI - Diphtheria acquired by U.S. citizens in the Russian Federation and Ukraine--1994. AB - Epidemic diphtheria has reemerged in 14 of the 15 New Independent States (NIS) of the former Soviet Union (1); during 1994, a provisional total of 47,802 cases and 1746 deaths from diphtheria were reported throughout the NIS. This report describes one confirmed and one probable case of diphtheria acquired in countries where the disease is epidemic (Russian Federation and Ukraine) by U.S. citizens during November and December 1994. PMID- 7885321 TI - Vaccination coverage surveys in county health departments--Kansas, 1993-1994. AB - The objective of the Childhood Immunization Initiative (CII) is to protect all children in the United States by their second birthday against nine vaccine preventable diseases. Specific objectives for 1994 were to increase coverage levels to at least 85% for the third dose of diphtheria and tetanus toxoids and pertussis vaccine (DTP3) and the first dose of measles, mumps, and rubella vaccine (MMR1); 75% for the third doses of oral poliovirus vaccine (OPV3) and Haemophilus influenzae type b vaccine (Hib3); and 30% for the third dose of hepatitis B vaccine (HepB3) (1). To determine whether county health departments in Kansas had achieved the national vaccination objectives, in 1993 staff from the Kansas Department of Health and Environment (KDHE) began assessing vaccination coverage rates for children aged 2 years served by county health departments in that state. This report presents the results of the first vaccination coverage assessments of all 105 county health departments in Kansas during November 1993-November 1994. PMID- 7885322 TI - [Ortho- and pyrophosphate in aerobic and anaerobic metabolism of erythrocytes (Biochem. Zeitschrift, 227, 16-38, 1930)]. PMID- 7885323 TI - [Correlation between respiration and conversion of pyrophosphate in avian erythrocytes (Biochem. Zeitschrift, 251, 343-368, 1932)]. PMID- 7885324 TI - [Myosin and adenosine triphosphatase (Nature, 144, 688, Oct. 14, 1939)]. PMID- 7885325 TI - [Physical mapping of the human genome: on the way to developing an optimal strategy]. AB - Physical mapping of the human genome appears to be a complicated problem for the molecular genetics of higher organisms. The difficulties are not only due to the great amount of work to be done, but mostly due to the peculiarities of genome organization (repeated nucleotide sequences, non-clonable, methylated and toxic fragments, etc.). Mapping procedures based on molecular hybridization do not allow to obtain the unambiguous results due to the occurrence of the repeats of different types common for the genome as a whole. Giant DNA fragments (e.g. YAC- Yeast Artificial Chromosomes) undergo deletions, transformations and chimerism and cannot be the main approach for genome mapping. The new strategy for genome mapping is described with reference to the human chromosome 3--one of the largest human chromosomes. The main steps of this new strategy are the following: 1) sequencing of STS (Sequence Tagged Sites) flanking DNA rare-cutting restriction sites; 2) alignment of the STS along the chromosomal DNA (generation of the contigs) based on the comparative computer analysis of STS from the same and from the neighboring restriction sites, 3) determination of the distance between STS by hybridization of large DNA fragments with STS. In order to apply this strategy called "shot-gun sequencing strategy for long range genome mapping" a new family of vectors (SK series) specially designed for the genome cloning was constructed and the simplified inexpensive technology for preparing the jumping/linking libraries was developed. Chromosome 3 fragments were sequenced around NotI sites, and the contigs covering about 50 Mbp of genomic DNA were constructed. The perspectives for the whole human genome mapping are discussed. PMID- 7885326 TI - [Ways of finding inhibitors of HIV reproduction among nucleotides]. AB - In spite of continuous broad search for inhibitors of HIV reproduction among new nucleosides, there seems to be a certain crisis in the problem. One of the probable solutions could be based on the investigation of nucleotide and/or nucleoside 5'-triphosphates with modified carbohydrate and phosphate residues. The review analyzes the current state of the problem, examining of such types of compounds in cell-free systems with DNA polymerases and in HIV-infected cell cultures. The known data on the stability and metabolism of such compounds in cell cultures as well as in human serum are also analyzed. PMID- 7885327 TI - [The A-form of DNA: in search of the biological role]. AB - Only recently first direct evidence for the involvement of the A-DNA in the biological processes and structures has been obtained. This was preceded by numerous studies during four decades, which revealed structural features of this second, next to the B-form, DNA conformation, the conditions for the B to A transition to occur in a tube, the requirements to nucleotide sequence. Due to these works the B-A cooperative transition in DNA is now understood as good as the DNA melting. The above physico-chemical studies forced one to think on the "biology" of the A-conformation and at the same time provided experimental possibilities for finding it in biological processes. PMID- 7885328 TI - [Antibody engineering]. PMID- 7885330 TI - [Identification of a Mycoplasma strain using fingerprinting of restriction enzyme hydrolysates of chromosomal DNA]. AB - The heterogeneity among Mycoplasma gallisepticum strains was characterized by comparing genomic DNA from different strains. Two criteria were used for the comparison. 1. Analysis of SmaI and BglI restriction patterns. A method using a dialysis sack for preparation of mycoplasma DNA suitable for pulsed-field gel electrophoresis is described. 2. Comparison of "fingerprinting" patterns obtained as a result of Southern transfer of HindIII-digested DNA followed by hybridization with cloned repetitive M. gallisepticum sequences. It was shown that both types of patterns analyzed are strain-specific; moreover, we were able to identify as a A5969 the strain of M. gallisepticum which was wrongly referred to as S6 in our previous works (Mol. Biol. 1991. V. 25. P. 1643-1649; FEBS Lett. 1991. V. 291. P. 71-74). PMID- 7885329 TI - [Restructuring of the spatial organization of circular DNA molecules in liquid crystal dispersions]. AB - The change in the spatial structure of superhelical and nicked DNA molecules in liquid-crystalline dispersions under micrococcal nuclease treatment was studied. Micrococcal nuclease digestion leads to restructuring from the "nonspecific" packing of circular DNA in dispersion particles to the cholesteric one. The transition is described by the Kolmogorov-Avramy equation; however, the parameters of the equation are essentially different for the different topological forms of circular DNA. The liquid-crystalline state of DNA expands the range of the solvent properties (ionic conditions etc.) under which the micrococcal nuclease action remain highly efficient. PMID- 7885331 TI - [A kinetic method of determining the frequency of homologous recombination of plasmids in Escherichia coli cells]. AB - To test the frequency of recombination by the RecF pathway the hybrid plasmids have been constructed which allow the bioluminescence recombination assay in the transformed E. coli cells. pF2(+) and pF6(+) are derivatives of pUC18 and pACYC184 respectively, with the luxA and luxB genes of Vibrio fischeri cloned downstream of the lac promoter. The luxA genes in pF2(+) and pF6(+) were mutated at the XhoI site and the HindIII site, accordingly, pF8 is a pACYC184 derivative with two copies luxA and luxB genes. The one copy of luxA gene was mutated at the XhoI site and another copy of the luxA gene was mutated at the HindIII site. A kinetic analysis of the population of the replicating and recombinating plasmids has been carried out. Experimental values of the frequency of recombination per one generation (P) were determined for the different E. coli strains. PMID- 7885332 TI - [Differentiation of the spatial mobility of lysine residues in immunoglobulin G using spin labels]. AB - Some dynamic and conformational changes of Lys residue in molecules of human IgG have been studied by the spin label method using N-(1-oxyl-2,2,5,5-tetramethyl-3- pyrrolidinyl)maleimide, known to selectively modify the Lys residue in human IgG. The value of tau 20 C of the spin labelled IgG was found to be 26 +/- 2 ns, what is known to be characteristic for the labelling of the peptide residue in IgG. It has also been found that the spin-labelled Lys residues exist in two forms with different mobility and rigidity with the ratio of mobile to rigid forms of 3:1. The hypothesis that the reason for immobility of Lys residues in IgG lies in their drawing in the H-bonds formation is being proved. The study by the spin label method has shown that the often observed mobilization of the EPR spectra of the spin labelled IgG is caused by the process of autolysis in the stored samples. The use of the phenylmethylsulfonylfluoride can completely eliminate this phenomena. PMID- 7885333 TI - [Effectiveness of a procedure for aligning sense sequences to make possible restoring the true alignment]. AB - The method is presented which may estimate the reliability of any alignment procedure on the basis of comparing between genuine alignment obtained by generating of appropriate sequences with the result of alignment procedure work. The opportunities of the method are illustrated by testing the OPAL286 program. Dependence of reliability of the results i.e. reconstruction of genuine alignment from percent of mutations and deletion-insertions are pointed. The method developed provides correct optimal choice of parameters for alignment procedure in the sense of reliability and probability of correct reconstruction of the original alignment. PMID- 7885334 TI - [The effect of ethanol on heat denaturation of pepsinogen]. AB - The effect of ethanol and medium pH on thermodynamic parameters and cooperativity of pepsinogen thermal denaturation have been studied by scanning microcalorimetry. Addition of 20% (v/v) ethanol decreases the protein temperature of denaturation by 10.7 degrees C at pH 6.4 and by 15.8 degrees C at pH 8.0. It decreases the denaturation heat capacity change of pepsinogen from 5.8 to 4.2 kcal/K.mol, but has no effect on the number of energetic domains (regions melting in an "all-or-none" manner). The dependences of calorimetric denaturation enthalpy on denaturation temperature in both aqueous solution and 20% ethanol are linear and converge at about 95 degrees C, which coincides with the converge temperature of similar dependencies shown for a number of proteins in aqueous and water-alcohol solutions. A change of pH from 5.9 to 8.2 in 20% ethanol has been shown to cause a decrease of the number of cooperatively melting regions in pepsinogen. This process involves no changes either in the secondary structure or in the local surroundings of aromatic amino acids. It is concluded that ethanol addition has no effect on pepsinogen denaturation cooperativity until there is sufficient influence on intramolecular charge distribution, taking place upon a change of pH. PMID- 7885335 TI - [The effect of specific deimination of glycogen phosphorylase b by peptidylarginine deiminase on the allosteric properties of the enzyme and dimer tetramer transition]. AB - The kinetics of the native glycogen phosphorylase b from rabbit skeletal muscle and of the enzyme specifically deiminated by peptidylarginine deiminase have been studied. According to the data on amino acid composition one arginine residue per phosphorylase b monomer is transformed into citrulline after 3 hours of incubation with peptidylarginine deiminase. The kinetics of the phosphorylase reaction were studied in the direction of glycogen synthesis. The native and the deiminated forms of phosphorylase b showed similar affinity to glucose 1 phosphate. The maximal velocity of the enzymatic reaction for the modified phosphorylase b is 8-20% higher than that for the native enzyme. Deiminated phosphorylase b like the native enzyme shows a positive kinetic cooperatively with respect to glucose 1-phosphate in the presence of the allosteric inhibitors (FMN, glucose), S-shaped dependences of the velocity of the enzymatic reaction on glucose 1-phosphate concentration (in the presence of FMN) pronouncing more distinctly for deiminated phosphorylase b than for the native enzyme (Hill coefficient is equal to 1.7 +/- 0.2 and 1.3 +/- 0.1, respectively). The affinity of the modified phosphorylase b to the allosteric activator AMP is one order of magnitude higher than that to the native enzyme. The cooperativity of AMP binding doesn't change significantly after deimination. The kinetics of inhibition of the native and modified phosphorylase b by FMN, glucose and glucose 6-phosphate are cooperative (the value of Hill coefficient is higher than unity). The more pronounced distinctions between two forms of the enzyme concern with the value of the "semisaturation" concentration [I]0.5. The deimination causes a pronounced reduction of the values of [I]0.5 for FMN and glucose, but the sensitivity of the deiminated enzyme to glucose 6-phosphate is much lower than that of the native phosphorylase b. Deiminated phosphorylase b unlike the native enzyme shows the positive cooperativity of the FMN binding (the value of the Hill coefficient is equal to 1.37 +/- 0.05). Deiminated phosphorylase b shows less capability to form tetramer in the presence of AMP as compared to the native enzyme. PMID- 7885336 TI - [A new method of comparative analysis of gene expression and identification of differentially expressed mRNA]. AB - A novel method of comparative gene expression analysis is proposed which is based on representing a population of expressed mRNA sequences in the form of a set of discrete cDNA restriction fragments. By means of selective isolation of 3' terminal cDNA fragments, each mRNA species is represented by no more than one cDNA fragment of specific length and sequence. Populations of cDNA fragments from different cell types are separated by high-resolution gel electrophoresis, and the separation patterns are compared. Using the proposed approach, fragments of two genes differentially expressed in murine thymus and spleen were identified and cloned. One of the genes was found to encode the terminal deoxynucleotidyltransferase, the there is apparently a heretofore unknown gene. PMID- 7885337 TI - [Detection of nonhistone proteins, bound with regulatory elements of yeast rRNA genes, by UV-crosslinks in intact nuclei]. AB - We have studied the arrangement of DNA-binding proteins along yeast ribosomal non transcribed spacer by UV-induced DNA-protein crosslinking on intact nuclei. We show binding of proteins with apparent Mw 120 and 30 kDa in promoter region, 120 kDa in enhancer region, 40 kDa in ARS. These proteins were identified preliminary as REB1 (promoter, enhancer), TFID (promoter), MCM3 (ARS). Good agreement between information supplied by this technics and literature data prove usefulness of our approach and make possibility for its wide appliance. PMID- 7885338 TI - [Design of de novo specific DNA-binding peptides, using the motif beta-chain-turn beta-chain for recognizing a nucleotide sequence in DNA]. AB - De novo design and synthesis by a solid phase technique of linear and cyclic 26 residues peptides are reported. The peptides use beta-strand-turn-beta -strand motif for sequence recognition on DNA. Amino acid sequences in the two peptides are identical, but the structure of the cyclic peptide is constrained by S-S bridge between two cysteine residues. A 28-residue peptide containing at the N terminus a copper-chelating peptide Gly-Gly-His is also synthesized which can be used as a potential DNA-cleaving reagent. Binding of these peptides to various natural and synthetic DNAs and DNA fragment with a known base pair sequence has been studied by CD spectroscopy, fluorescence methods and DNAse I footprinting technique. By means of CD spectroscopy it is shown that 26-residue linear and cyclic peptides are partially in disordered and beta-conformations in aqueous solution in absence and in presence of 20% trifluoroethanol (TFE), but assume partially an alpha-helix conformation in the presence of 50% TFE. It is shown that linear and cyclic peptides bind to DNA. The binding approaches saturation level when one peptide molecule is bound approximately per three or four DNA base pairs. We found that antibiotic distamycin A, binding in the minor DNA groove, competes effectively with the 26-residue linear and cyclic peptides for binding to poly(dA).poly (dT). According to the CD spectroscopy data the linear and cyclic peptides undergo conformation changes upon binding to DNA, whereas the DNA structure is not markedly altered. Difference CD spectra obtained by subtracting the spectrum of the free DNA from the spectrum of the peptide-DNA mixture differ from the spectrum of the free peptide. The shapes of difference CD spectra are consistent with a conformation transition from a disordered conformation into a beta-like conformation upon binding of peptide to DNA. DNAase I footprinting diagrams show that there is a specific protection by linear and cyclic peptides of the nucleotide sequences on two ends of operators OR1, OR2 and OR3 and pseudooperators within the cro gene of 434 phage. PMID- 7885339 TI - [How and why is pepsin stable and active at pH 2?]. AB - The HCl in the mammalian stomach is concentrated enough to digest the stomach itself and to cause denaturation of proteins. The paper summarize studies which explain why the gastric epithelium remains undamaged and gastric proteinase pepsin has the most stable and active structure at such extreme conditions. Pepsin is the first proteinase which starts protein proteolysis during the multistep process of protein digestion, and it splits mainly their hydrophobic cores unfolded in acidic media. Data on the disposition of the charged groups in the three-dimension structure of pepsin, which explain the extraordinary properties of the enzyme, are discussed. PMID- 7885340 TI - [Study of the quaternary structure of glutamate carboxylase from Escherichia coli]. AB - It was shown by electron microscopy, that the native molecule of glutamate decarboxylase is a hexamer with dihedral symmetry; the subunits are situated at the apices of an octahedron. Apoenzyme at pH 6.0 is dissociated form. It were found s20.w - 12.8 +/- 0.54S and 5.51 +/- 0.43S for the native hexamer and a dissociated form, respectively. By column gel-filtration the molecular mass of the dissociated form was estimated as 105-106 kDa, this value corresponds to a dimer. There were 10 buried SH-groups per subunit in the hexamer, after dimer formation 8 of them became accessible. The reversible hexamer-dimer dissociation depends on pH and PLP. The pH dependences of the enzyme dissociation and activity are very similar. In the result of adding of 6 PLP equivalents to the dimers the reactivation and hexamer assembly were reached, the SH-groups burying preceded both these reactions. Effect of pH and PLP on the quaternary structure is known for some other PLP-enzymes. It may be the additional proof for the idea of a common ancestor for PLP-enzymes. PMID- 7885341 TI - [Attainment of an energy minimum by a protein chain does not require a complete sorting of conformations: a computerized experiment and phenomenological theory]. AB - We investigate how a protein chain achieves the lowest energy state by Monte Carlo simulation using a simple beta-sheet protein model. We show the existence of an optimal temperature range where the energy minimum is found quickly without any exhaustive sorting of the chain conformations even for random sequences. This optimal temperature range is determined by the critical temperature characteristic for the onset of freezing-out of a few lowest-energy chain folds. A simple phenomenological model is presented to account for this behavior of the protein chain. PMID- 7885342 TI - Striatal dihydroxyphenylalanine decarboxylase and tyrosine hydroxylase protein in idiopathic Parkinson's disease and dominantly inherited olivopontocerebellar atrophy. AB - We measured the levels of dopamine, tyrosine hydroxylase (TH) protein, and dihydroxyphenylalanine (DOPA) decarboxylase (DDC) protein in the striatum of 10 patients with idiopathic Parkinson's disease (PD) and 23 patients with dominantly inherited olivopontocerebellar atrophy (OPCA). The levels of dopamine were markedly reduced (2% of control) in the striatum of the patients with PD, whereas striatal dopamine in the patients with OPCA ranged from normal (> 60% of control) to moderately reduced (20-60% of control) to severely depleted (< 20% of control). Both TH and DDC protein levels were significantly lower than those of the controls in the striatum of all of the patients with PD and in the subgroup of patients with OPCA having severely depleted dopamine. In contradistinction, TH but not DDC protein levels were reduced in those patients with OPCA having moderately reduced dopamine levels. This suggests that in the early stage of nigrostriatal dopamine neurone degeneration, DDC levels may be less susceptible to neurodegenerative influences than is TH synthesis or, alternatively, DDC synthesis may be more aggressively upregulated. Unexpectedly, from the blot immunolabeling analysis an additional DDC-immunoreactive band of slightly lower apparent molecular mass was detected in two of the patients with PD and in 12 of the patients with OPCA. This additional DDC band, which was not present in any of the control subjects, may reflect posttranslational modification(s) of DDC related to the neurodegenerative process. PMID- 7885343 TI - Tourettism associated with Huntington's disease. AB - The identification of the gene for Huntington's disease (HD) has made it possible to diagnose patients with HD who present with unusual or atypical features. We describe a 41-year-old man whose initial manifestation of HD was dominated by the presence of motor and vocal tics and other features of Tourette's syndrome. This case illustrates the broad range of clinical manifestation of HD and the usefulness of testing for the HD mutation in selected cases with familial movement disorders. PMID- 7885344 TI - Psychiatric symptoms, atypical dementia, and left visual field inattention in corticobasal ganglionic degeneration. AB - We longitudinally examined the neuropsychological and psychiatric characteristics of an adult male with pathologically confirmed corticobasal ganglionic degeneration (CBGD). The patient was seen on an inpatient and outpatient basis by members of the Departments of Neurology and Radiology of the University of Miami School of Medicine. Longitudinal neuropsychological testing revealed a lateralized cortical-subcortical dementia and left visual field inattention consistent with neurological and postmortem neuropathological findings of greater right hemisphere dysfunction. Symptoms of depression and obsessive-compulsive symptomatology were also documented. Our findings are consistent with prior reports indicating that CBGD is characterized by lateralized cerebral dysfunction and suggest that a detailed neuropsychological examination is a useful procedure to assist in the differential diagnosis of this movement disorder. PMID- 7885345 TI - Morphological overlap between corticobasal degeneration and Pick's disease: a clinicopathological report. AB - An 81-year-old woman died after a 3-year history of a progressive nondementing akinetic-rigid syndrome. Initially, there was a moderate response to levodopa treatment. Subsequently she developed postural tremor, loss of upward gaze, and frequent falls suggestive of Steele-Richardson-Olszewski syndrome (SROS). Macroscopical examination showed depigmentation of substantia nigra and locus ceruleus. Histology revealed occasional swollen achromatic neurons predominantly in frontal cortex, small cortical neurofibrillary tangles, brain stem basophil (corticobasal) inclusions, and Pick bodies. The coexistence of these histopathological markers raises questions concerning their specificity and the basis of a morphological distinction between corticobasal degeneration and Pick's disease. PMID- 7885346 TI - Levodopa in pregnancy. PMID- 7885347 TI - Parkinsonism induced by amlodipine. PMID- 7885348 TI - Thalamic lacune and contralateral hemiparkinsonism subsequently relieved by spontaneous thalamo-subthalamic hematoma. PMID- 7885349 TI - Congenital mirror movements. PMID- 7885350 TI - The bereitschaftspotential preceding stepping in patients with isolated gait ignition failure. AB - The cerebral activity preceding voluntary, self-paced ankle dorsiflexion movements while seated was compared with that before a stepping movement of the same foot while standing in four patients with isolated gait ignition failure. Results within the patients group were variable, but all exhibited some increase in the Bereitschaftspotential (BP) amplitude when stepping as compared with sitting, similar to that seen in normal subjects. This differs from previous results in patients with Parkinson's disease in which stepping was not accompanied by a normal increase in BP amplitude. This difference suggests that the mechanisms responsible for the start hesitation that is common to both Parkinson's disease and gait ignition failure may differ in the two conditions. PMID- 7885351 TI - Evidence of peripheral axonal neuropathy in primary restless legs syndrome. AB - Restless legs syndrome (RLS) is a well-defined clinical entity characterized by an unpleasant creeping sensation arising in the legs with an irresistible need to move them. The trouble is more pronounced when the affected people lie in a prolonged rest position and try to fall asleep. It is known that RLS may be consequent to systemic disorders and to diseases affecting the central or peripheral nervous system. The International Classification of Sleep Disorders states that peripheral neuropathy should be ruled out by medical history and clinical grounds before diagnosing primary RLS (pRLS). The present study extended peripheral nerve investigation in eight consecutive pRLS patients with normal neurological examination results and showed that all patients exhibited two or more electrical, psychophysiological, and/or morphological features of peripheral axonal neuropathy. Morphometric analysis of sural nerve showed a significant reduction in myelinated fiber density and g ratio (axon diameter/fiber diameter) in the pRLS group compared with eight control biopsy specimens. These results suggest that axonal neuropathy is often present in patients with RLS. A comprehensive peripheral nerve investigation should be considered in RLS patients. PMID- 7885352 TI - The movement disorder of adult opsoclonus. AB - We present three cases of the adult opsoclonus-myoclonus syndrome in patients with systemic carcinoma. In addition to opsoclonus and myoclonus, other clinical components of the syndrome can include ataxia, tremor, gait and stance dysfunction, altered mental status, and head and face dyskinesias. The most common etiologies are idiopathic, paraneoplastic, and infectious encephalitis. Radiographic and pathological studies suggest brain-stem dysfunction with associated cerebellar and/or cerebellar pathway dysfunction. In many cases, there is evidence for the involvement of immunologic and/or inflammatory processes in the pathogenesis of this syndrome. The timely recognition of this syndrome is important because of its implications for the underlying etiology and prognosis. The appearance of this syndrome should prompt the search for an occult malignancy. PMID- 7885353 TI - Peripheral and central pharmacokinetics of apomorphine and its effect on dopamine metabolism in humans. AB - Apomorphine is a dopamine receptor agonist increasingly used in the treatment of Parkinson's disease (PD). In the present study, we examined the plasma and ventricular cerebrospinal fluid (CSF) pharmacokinetics of apomorphine as well as its effects on dopamine metabolism in six patients (one woman and five men, mean age 79.5 years) without evidence of PD who underwent 48-h intracranial pressure monitoring for suspected normal pressure hydrocephalus. Maximal plasma apomorphine concentration (25.04 ng/ml) is found 20 min after subcutaneous injection (50 micrograms/kg), and the mean area under the curve is 1,439.37 ng/ml for 120 min. In contrast to plasma values, the maximal ventricular CSF apomorphine concentration (1.08 ng/ml) is found 30 min after injection and the mean area under that curve is 7% of that of plasma (96.69 ng/ml for 120 min). Apomorphine administration causes a significant reduction in ventricular CSF concentrations of dopamine and of its major metabolites sulfoconjugated dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA). This effect starts 10 min after the injection of apomorphine, is maximal after 30 min (free dopamine, -30%; sulfoconjugated dopamine, -28%; HVA, -21%; DOPAC, -31%) and is still present, although to a lesser extent (-5 to -10%), 120 min after the injection of apomorphine. This study shows that in humans a dose of apomorphine commonly used in PD causes significant inhibition of dopamine metabolism lasting > 120 min. In addition to their symptomatic effects, dopamine agonists such as apomorphine may play a role in preventing or slowing the neurodegeneration in PD by autoreceptor-mediated inhibition of dopamine metabolism. PMID- 7885354 TI - Apomorphine infusional therapy in Parkinson's disease: clinical utility and lack of tolerance. AB - We assessed the clinical utility of apomorphine infusional therapy in patients with parkinsonism and motor fluctuations and sought evidence for alterations in drug response resulting from chronic treatment. Six patients with Parkinson's disease were treated for 3 months with s.c. infusions of apomorphine administered during waking hours. At the beginning and the end of the study, test doses of apomorphine (12.5-100 micrograms/kg) were administered to establish a dose response curve. Over the study, the patients reported a significant improvement in the number of "on" hours experienced per day and substantially reduced the dose and frequency of levodopa and other antiparkinsonian medications. No average change in apomorphine dose-response relationships or pharmacokinetics was observed during the study. However, two patients lowered the infusion rate during the 3-month observation and exhibited higher drug levels and longer responses following test doses of apomorphine given at the end of the study. Although pragmatic concerns with the use of infusion pumps solutions and adverse effects limited the overall benefit afforded by the treatment, this kind of drug treatment may be useful in selected patients with severe parkinsonism and fluctuations. PMID- 7885355 TI - Soleus H-reflex tests in dystonia. AB - Vibratory inhibition, the homonymous recovery curve and the ratio of the maximal H-reflex to direct muscle potential (H/M ratio) of the soleus H-reflex were assessed in 10 patients with leg dystonia and in six patients with arm or neck dystonia. The results were compared with those obtained in 48 healthy control subjects. H-reflex variables most helpful for the discrimination of patients and healthy subjects were identified. In patients with leg dystonia, vibratory inhibition was less marked than in control subjects, whereas late facilitation of the recovery curve was increased. In patients with leg dystonia, area values of test reflexes in the late facilitatory phase of the recovery curve exceeded peak peak values, in contrast to findings in control subjects. This finding may be attributable to less synchronization of enhanced test reflexes in dystonia than in the control condition. In differentiating patients with leg dystonia from control subjects, a combination of parameters of vibratory inhibition and the late facilitatory phase of the recovery curve appeared most useful. In patients with arm or neck dystonia and in the unaffected legs of hemidystonic patients, soleus H-reflex test results were in the normal range. Abnormalities in the results of the soleus H-reflex tests we used appear to be related to the presence of clinical signs in the extremity under examination and not to the severity of features. PMID- 7885356 TI - Associative learning in degenerative neostriatal disorders: contrasts in explicit and implicit remembering between Parkinson's and Huntington's diseases. AB - The performances of 12 patients with Parkinson's disease (PD), 16 with Huntington's disease (HD), and young and old healthy controls were assessed on a number of tests of verbal and nonverbal declarative memory, on a test of nonmotor conditional associative learning (words and colors), and on a number of reaction time (RT) tasks. The RT tasks consisted of cued simple and choice reactions. The relationship between the precue and the imperative stimulus in the S1-S2 paradigm was nonarbitrary in the first series and arbitrary in the second series. The series with arbitrary S1-S2 associations was repeated across two successive blocks of trials. The rationale of the study was to investigate the function of the basal ganglia "complex loop," and it was postulated that HD patients would show greater deficits because of greater involvement of the caudate nucleus. The patients with HD had the slowest RTs. Across the two blocks with arbitrary S1-S2 associations, the patients with HD but not PD nevertheless showed evidence of learning in their precued RTs. In contrast, the patients with PD were better able to remember the associations in free recall than were the HD patients. It is concluded that patients with PD have relatively greater deficits in procedural learning, whereas those with HD have relatively more impairments in declarative memory, and the greater level of cognitive impairment in HD overall is interpreted as being due to more serious damage to the caudate loop. PMID- 7885357 TI - The effects of cisapride on plasma L-dopa levels and clinical response in Parkinson's disease. AB - Cisapride (CIS) is a prokinetic agent that increases gastrointestinal motility in normal individuals and improves constipation in Parkinson's disease (PD). We studied the effects of CIS on the clinical response and the peripheral pharmacokinetics of orally administered L-dopa given to patients with PD. Twenty patients with idiopathic PD and chronic constipation, whose response to L-dopa was suboptimal or characterized by fluctuations, agreed to participate in an open study that lasted for 2 weeks. Fourteen patients completed the study (mean age 65 +/- 9.3 years, mean duration of treatment 5.7 +/- 4.2 years, mean L-dopa daily doses 658.9 +/- 269.9 mg); six patients were excluded due to lack of compliance or changes in medication during the study. The end points of the study included the mean levels of L-dopa, the height of the peak of L-dopa in plasma, mean plasma levels of 3-OM-dopa, and the speed and quality of gait and visuomanual coordination before and during treatment with CIS. CIS increased peak plasma levels of L-dopa by 37% and the mean plasma levels of L-dopa by 13% with respect to those obtained with the same dose of L-dopa before the addition of CIS. Therefore, CIS appears to increase early absorption of L-dopa through acceleration of gastric emptying. CIS also increased plasma 3-OM-dopa levels, improved visuomanual coordination, and reduced gait disability. CIS improves gastrointestinal function and response to L-dopa in patients with PD and could be a helpful add-on medication in these patients. PMID- 7885358 TI - The abnormality of N30 somatosensory evoked potential in idiopathic Parkinson's disease is unrelated to disease stage or clinical scores and insensitive to dopamine manipulations. AB - We recorded short latency somatosensory evoked potentials (SEPs) to median nerve stimuli in 40 patients affected by idiopathic Parkinson's disease (PD) classified from I to IV on the Hoehn and Yahr disability scale. SEPs were recorded before and after chronic administration of L-Dopa and bromocriptine, before and after acute administration of L-Dopa. Fourteen patients experiencing wearing off and dystonic-dyskinetic disturbances were recorded during the occurrence of these oscillations of their clinical status. Absent or reduced N30 components were found in 32.5% of patients. SEPs were not modified by acute or chronic administration of L-Dopa or bromocriptine or during off and dystonic or dyskinetic conditions. Multiple correlations of N30 with scores of the Unified Parkinson's Disease Rating Scale showed that N30 abnormality did not classify patients with prominent clinical features, nor did it predict the outcome of treatment. PMID- 7885359 TI - Effect of cisapride on response fluctuations in Parkinson's disease. AB - Impaired gastric emptying may be the cause for some response fluctuations in Parkinson's disease (PD), especially the "delayed-on" and "no-on" phenomena. Cisapride is a prokinetic drug that enhances gastric emptying by releasing acetylcholine from the myenteric plexus. Tolerability and safety as well as efficacy of cisapride was studied in an open-label trial on 15 fluctuating PD patients. Twelve patients had "delayed-on" and six had "no-no" phenomena. They filled out daily diaries on times of levodopa intake and of turning "on" and "off" for 1 week on levodopa alone and for an additional week of pretreatment with cisapride, 30 min before early morning, early afternoon, and late evening doses of levodopa. Cisapride significantly shortened latency to "on" from 60 +/- 20 to 45 +/- 19 min after the morning dose and from 63 +/- 17 to 47 +/- 22 min after the evening doses. Patients with "no-no" phenomenon had a decreased number of dose failures from 23 before to nine during cisapride treatment. The drug was well tolerated, with no important side effects. Our study supports the role of impaired gastric emptying in some subtypes of motor fluctuations and indicates that they may be improved by prokinetic drugs. PMID- 7885360 TI - Frontal and parietal premovement slow brain potentials in Parkinson's disease and aging. AB - During the anticipation of a stimulus that induces a predetermined pattern of behavior, a slowly increasing negative electric potential can be recorded from the human scalp at central and parietal electrodes and has been named contingent negative variation (CNV). We used a simple and a choice reaction time paradigm to investigate premovement potentials in patients with Parkinson's disease (PD) and in normal controls. There was a clear CNV in young subjects whereas it was negligible in the elderly control subjects and absent in the patients. In addition, we found a slowly increasing positive frontal potential. In normals the steepness of this potential decreased with the complexity of the task (simple vs. choice) and with age. This difference was abolished in the patients: If a slowly increasing positivity was observed at all, it was, on average, larger in the choice task. Reaction times of the patients were disproportionally prolonged in the simple compared to the complex task. These findings support the hypothesis that storing or initiating a simple preprogrammed motor response is more impaired in PD than selecting and initiating a motor response of a more complex task. The electrophysiological recordings suggest that impaired activation of the frontal lobes may be responsible for this deficit. PMID- 7885361 TI - Gonadal sex hormones and dystonia: experimental studies in genetically dystonic hamsters. AB - In some kinds of idiopathic dystonia, including paroxysmal dystonia, a role of sex hormones has been suggested because of female predominance and onset, recurrence, or exacerbation of dystonic symptoms with pregnancy. Similar effects of pregnancy have recently been reported in a model of paroxysmal dystonia, the genetically dystonic hamster. Dystonia in mutant hamsters of both genders is transient, i.e., exhibits spontaneous remission at around puberty, strongly suggesting involvement of gonadal sex hormones. For exploration of the role of sex hormones in dystonia, we undertook a series of ontogenetic experiments in male and female dystonic hamsters. Mutant animals of both genders exhibited the same postnatal development of dystonia with maximum severity of dystonic attacks between weaning and approximately 40 days of age and spontaneous remission thereafter. As shown by plasma sex hormone determinations and, in females, vaginal cytology, spontaneous improvement of the movement disorder coincided with puberty in both genders. Male and female hamsters had about the same plasma levels of progesterone. Compared with nondystonic hamsters, onset of puberty was significantly retarded in both male and female dystonic hamsters. Furthermore, body weight gain was lower in dystonic animals, indicating retarded postnatal development. Gonadectomy at time of weaning did not alter the age-dependent development and remission of dystonia, suggesting that gonadal sex hormones are not critically involved in the disease in hamsters. We propose that transient paroxysmal dystonia in mutant hamsters is caused by postnatal retardation of brain development resulting in a temporary impairment of brain functions with spontaneous remission independent of gonadal sex hormones. In view of the fact that the brain can synthesize steroids such as progesterone independent of peripheral glands in both genders, such neurosteroids might be involved in the postnatal brain maturation that leads to remission of dystonia at around puberty in mutant hamsters. PMID- 7885362 TI - Polycyclic aromatic hydrocarbon-DNA and protein adducts in coal tar treated patients and controls and their relationship to glutathione S-transferase genotype. AB - Coal tar treated psoriasis patients were used as a model population to evaluate a panel of immunoassays for monitoring exposure to benzo[a]pyrene (BP) and related polycyclic aromatic hydrocarbons (PAH). The assays included measurement of PAH diol epoxide-DNA adducts in white blood cells by competitive enzyme-linked immunosorbent assay (ELISA) with fluorescence endpoint detection, PAH-albumin adducts by competitive ELISA with color endpoint detection and serum levels of antibodies recognizing BP diol epoxide-DNA adducts by noncompetitive color ELISA. PAH-DNA adducts by ELISA were elevated in patients (mean 6.77 +/- 12.05/10(8)) compared to controls (4.90 +/- 8.81/10(8), p = 0.12). There was no difference in PAH-albumin adducts between patients (mean 0.61 +/- 0.31 fmol/micrograms) and controls (0.63 +/- 0.30 fmol/micrograms). Glutathione S-transferase M1 genotype was also determined but no relationship was found between presence of the gene and either DNA or protein adduct levels. About 30% of both patients and controls had measurable titer of antibodies recognizing BPDE-I-DNA adducts. Measurement of white blood cell DNA adducts by ELISA was the most sensitive method for detecting PAH exposure in coal tar-treated psoriasis patients. PMID- 7885363 TI - Chromosome aberrations and response to gamma-ray challenge in lymphocytes of workers exposed to 1,3-butadiene. AB - An integrated population monitoring study was initiated to investigate whether occupational exposure to current low levels of butadiene is mutagenic to workers. Ten exposed workers (mean production area concentration of 3.5 ppm) and 10 matched plant controls (mean exposure to 0.03 ppm) were selected and blood samples were collected for our study. The standard cytogenetic assay was used to determine chromosome aberration frequencies. In addition, a challenge assay was used to determine response to gamma-rays as an indication of DNA repair deficiencies. In the latter assay, cells were exposed to gamma-rays at the G1 phase of the cell cycle in vitro and the frequencies of chromosome aberrations in the first post-irradiation metaphase cells were quantitated. Based on results of the cytogenetic assay, the exposed group had a higher frequency of cells with chromosome aberrations and higher chromatid breaks per 100 cells compared with the control. However, the difference was not significant (p > 0.1). With the challenge assay, the exposed group had a higher frequency of aberrant cells (p < 0.04), chromatid breaks (p < 0.05), deletions (p < 0.07), and dicentrics (p < 0.02) than the controls. In addition, the dicentric frequencies from workers were significantly correlated with the presence of a butadiene metabolite [1,2 dihydroxy-4-(N-acetylcysteinyl-S)butane] in urine with a correlation of coefficient of 0.6 (p < 0.01). Two outliers were identified and our interpretation of their responses will be discussed. This study indicates that the workers had exposure-induced mutagenic effects. Together with the observation of gene mutation in a subset of the present population, this study indicates that the current occupational exposure to butadiene may not be safe to workers. PMID- 7885364 TI - Inhaled radon-induced genotoxicity in Wistar rat, Syrian hamster, and Chinese hamster deep-lung fibroblasts in vivo. AB - This study was performed (1) to provide a comparison of the genotoxic effects of inhaled radon and radon progeny, referred to as radon in this paper, among three species of rodents: Wistar rats, Syrian hamsters, and Chinese hamsters; (2) to determine if initial chromosome damage was related to the risk of induction of lung cancer; and (3) to evaluate the tissue repair and long-term presence of cytogenetic damage in respiratory tract cells. These species were selected because Syrian hamsters are very resistant to radon induction of lung cancer and Wistar rats are sensitive; no literature is available on the in vivo effects of radon in the Chinese hamster. Exposure-response relationships were established for the rats and Syrian hamsters while the Chinese hamsters received a single exposure of radon. At 4 h (0.2 days), 15 days, and 30 days after the highest WLM exposure to radon, Wistar rats, Chinese hamsters, and Syrian hamsters were killed, and lung fibroblasts were isolated and grown in culture to determine the frequency of induced micronuclei. Animals at each level of exposure showed an increase in the frequency of micronuclei relative to that in controls (P < 0.05). The exposure-response relationship data for rats and Syrian hamsters killed 0.2 days after the end of exposure were fit to linear equations (micronuclei/1000 binucleated cells = 15.5 +/- 14.4 + 0.53 +/- 0.06 WLM and 38.3 +/- 15.1 + 0.80 +/ 0.08 WLM, respectively). For the single exposure level used (496 WLM) in Chinese hamsters killed at 0.2 days after exposure, the frequency of micronuclei/1000 binucleated cells/WLM was 1.83 +/- 0.02. A comparison of the sensitivity for induction of micronuclei/WLM illustrated that Chinese hamsters were three times more sensitive than rats. The Syrian hamsters also showed a significantly elevated response (P < 0.05) relative to rats. These data suggest that initial chromosome damage is not the major factor responsible for the high rate of radon induced cancer in rats relative to Syrian hamsters. The frequency of micronuclei in radon-exposed rats, Syrian hamsters, and Chinese hamsters significantly decreased (P < 0.05) as a function of time after the exposure. The rate of loss of damaged cells from the lung was greatest in the Chinese hamsters, followed by Wistar rats and Syrian hamsters, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7885365 TI - Occupational exposure to bidi tobacco increases chromosomal aberrations in tobacco processors. AB - In India, workers engaged in processing of tobacco for the manufacture of bidis (the indigenous substitute for cigarettes) are chronically exposed to tobacco flakes and dust via the cutaneous and nasopharyngeal routes. Hence, workers in a tobacco processing factory were monitored for chromosomal aberrations (CA) using peripheral blood lymphocytes as the test system. Cytogenetic analysis revealed a significant increase in deletion fragments and chromatid gaps in the exposed group. The frequency of aberrant metaphases and the proportion of individuals with CA were significantly higher in workers than in controls, indicating that occupational exposure to tobacco imposes considerable genotoxicity among tobacco processors. PMID- 7885367 TI - Effects of caffeine or EDTA post-treatment on EMS mutagenesis in soybean. AB - Seeds of soybean cultivar LD4 were mutagenically treated with EMS (0.3, 0.5, 0.6, 0.9, 1.5 and 1.8%) for 3 h only or plus caffeine (50 mM) or EDTA (1 mM) post treatment for 5 h. The experimental results indicated that: (1) of the different concentrations of EMS treatment, the M2 mutation frequency induced with 0.6% EMS was the highest (9.7%). When the EMS concentration was over 0.9%, the mutation frequency decreased rapidly. (2) Of the EMS treatments plus caffeine or EDTA post treatment, the mutagenic effect of 0.6% EMS was the best for inducing morphological variations. Caffeine post-treatment decreased notably the mutation frequency of EMS treatment; when concentrations of EMS were very high (1.5% and 1.8%), mutation frequencies of EDTA post-treatment were still 5.0% and 4.88%, but no mutants were found in EMS treatment or plus caffeine post-treatment. (3) In the M2 mutation spectrum, 11 kinds of mutant types were observed in EMS treatment or plus caffeine or EDTA post-treatment. Relative frequencies of some mutant types (growth period, plant height, grain size, leaf shape and sterility, etc.) were similar among the three treatments, but EDTA post-treatment could change the relative frequencies of yield characteristics (number of pods and grains, grain weight/plant) induced by EMS treatment only. PMID- 7885366 TI - Development of high sensitive umu test system: rapid detection of genotoxicity of promutagenic aromatic amines by Salmonella typhimurium strain NM2009 possessing high O-acetyltransferase activity. AB - A highly sensitive umu test system for the detection of carcinogenic/mutagenic aromatic amines has been developed utilizing a new tester strain, Salmonella typhimurium NM2009, possessing an elevated O-acetyltransferase (O-AT) level. NM2009 was constructed by subcloning the bacterial O-AT gene into a plasmid vector pACYC184 and introducing the plasmid into the original strain S. typhimurium TA1535/pSK1002 harboring an umuC'-'lacZ fusion gene. The system is based on the ability of DNA-damaging agents (genotoxins) to induce umuC gene expression and monitored by measuring the cellular beta-galactosidase activity evoked by the fusion gene. Twenty-two aromatic amine compounds including arylamines, aminoazo dyes, and heterocyclic aromatic amines were tested for inducibility of DNA damage after metabolic activation by rat liver S9 in strain NM2009 and the sensitivity was compared with those of the parent strain TA1535/pSK1002 and the O-AT-defective strain NM2000. NM2009 had about 400 times higher O-AT activity than the parent strain. It was found that NM2009 was much more sensitive to aromatic amines than other strains to induce umuC gene expression after metabolic activation; the chemicals which were extremely sensitive in strain NM2009 include 2-aminoanthracene, 2-aminofluorene, 2 acetylaminofluorene, benzidine, 6-aminochrysene, 2,4-diaminotoluene, 2,6 diaminotoluene, 1-naphthylamine, o-tolidine, 3-MeO-AAB, o-aminoazotoluene, Glu-P 1, Trp-P-1, MeA alpha C, A alpha C, MeIQ, MeIQx, and IQ. In contrast, Trp-P-2 and PhIP showed almost similar sensitivities in three tester strains used in this study. These results suggest that strain NM2009 with high O-acetyltransferase activity is very useful to detect the genotoxic activities of potential mutagenic aromatic amine compounds, which require metabolic activation via the cytochrome P 450/acetyltransferase system. PMID- 7885368 TI - Development of a rat cell line containing stably integrated copies of a lambda/lacI shuttle vector. AB - A rat embryo cultured cell line was generated that carries stably integrated copies of a lambda/lacI shuttle vector, containing the lacI gene as a mutational target. After the desired treatment of the cells, this vector can be rapidly and efficiently recovered from the cell DNA by in vitro packaging and then screened for mutations in the lacI gene, using bacterial detection systems. The vector is identical to that integrated into the Big Blue transgenic mouse, which was developed for in vivo mutation analysis. Characterization of the cell line by fluorescence in situ hybridization showed that the phage DNA is integrated at two distinct sites on separate chromosomes at approximately 50-70 copies per cell and the cell line is polyploid. The rescue efficiency is approximately 100,000 pfu/micrograms of genomic DNA. To examine the ability of the cell line to detect mutations in the lacI gene, the cells were treated with 100 micrograms/ml of the direct-acting alkylating agent N-methyl-N-nitrosourea (MNU) for 30 min at 37 degrees C and grown to confluence. The shuttle vector was rescued from untreated and mutagen treated cells, and spontaneous and induced mutant frequencies were determined to be 4.0 x 10(-5) and 92.7 x 10(-5), respectively. The cell line can be used to detect mutations in the lacI gene, followed by recovery of mutants for sequence analysis. The cell line may be valuable for short-term in vitro mutagenesis studies, oncogene and tumor suppressor studies, and DNA repair studies. PMID- 7885369 TI - Use of chick, Gallus domesticus, as an in vivo model for the study of chromosome aberration: a study with mitomycin C and probable location of a 'hot spot'. AB - A model bone marrow chromosome aberration test using the chick, Gallus domesticus, is described. The well known reference mutagen mitomycin C was used as the test chemical. Bone marrow chromosomal preparations were investigated after acute (0.5, 1.0, 2.0, 3.5 and 5.0 mg/kg b.w.) doses for dose-response and sub-acute (0.4 mg/kg/day, 5 days) doses for chronic studies. Only a single dose (2 mg/kg b.w.) was employed for time-response (6, 24 and 48 h) and route-response (i.p. and p.o.) studies. All the treated results differed significantly from the respective control value. The present results also revealed the location of a 'hot spot' in chromosome 4. The test is less expensive, more sensitive and reliable and easier than mouse model. This chick mutagenicity test model can be used as an alternative in vivo system for testing the mutagenicity of environmental pollutants. PMID- 7885370 TI - Cytogenetic study of tuberculosis patients before and after tuberculostatic drug treatment. AB - Cytogenetic analyses were carried out in lymphocytes of 15 untreated tuberculosis (tb) patients and 15 other tb patients who had received combined tuberculostatic chemotherapy HRZ (isoniazid+rifampicin+pyrazinamide) for 2 months. The frequency of chromosomal aberrations and sister-chromatid exchanges (SCEs) did not show any statistically significant differences in the patients before treatment and after exposure to combined HRZ therapy as compared to controls (p > 0.05). However, we observed that the mitotic index was significantly decreased in both groups (p < 0.05). Based on the results of the present study, we believe there is no indication for a chromosome damaging effect of HRZ and their metabolites in human lymphocytes in vivo after treatment of tuberculosis patients with optimum doses. PMID- 7885371 TI - The improved Allium/Vicia root tip micronucleus assay for clastogenicity of environmental pollutants. AB - The meristematic mitotic cells of plant roots are appropriate and efficient cytogenetic materials for the detection of clastogenicity of environmental pollutants, especially for in situ monitoring of water contaminants. Among several cytological endpoints in these fast dividing cells, such as chromosome/chromatid aberrations, sister-chromatid exchanges and micronuclei, the most effective and simplest indicator of cytological damage is micronucleus formation. Although the Allium cepa and Vicia faba root meristem micronucleus assays (Allium/Vicia root MCN) have been used in clastogenicity studies about 12 times by various authors in the last 25 years, there is no report on the comparison of the efficiency of these two plant systems and in different cell populations (meristem and F1) of the root tip as well as under adequate recovery duration. In order to maximize the efficiency of these bioassays, the current study was designed to compare the Allium and the Vicia root MCN assays on the basis of chromosome length, peak sensitivity of the mitotic cells, and the regions of the root tip where the MCN are formed. The total length of the 2n complement of Allium chromosomes is 14.4 microns and the total length of the 2n complement of Vicia is 9.32 microns. The peak sensitivity determined by serial fixation at 12-h intervals after 100 R of X-irradiation is 44 h. The slope of the X-ray dose-response curve of Allium roots derived from the meristematic regions was lower than that derived from cells in the F1 region. Higher efficiency was also demonstrated when the MCN frequencies were scored from the F1 cells in both Allium and Vicia treated with formaldehyde (FA), mitomycin C (MMC), and maleic hydrazide (MH). The results indicated that scoring of MCN frequencies from the F1 cell region of the root tip was more efficient than scoring from the meristematic region. The X-ray linear regression dose-response curves were established in both Allium and Vicia cell systems and the coefficients of correlations, slope values were used to verify the reliability and efficiency of these two plant cell systems. Based on the dose-response slope value of 0.894 for Allium and 0.643 for Vicia, the Allium root MCN was a more efficient test system. The greater sensitivity of the Allium roots is probably due to the greater total length of the diploid complement and the higher number of metacentric chromosomes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7885372 TI - Effect of radiation and cigarette smoking on expression of FUdR-inducible common fragile sites in human peripheral lymphocytes. AB - In vitro X-irradiation of human peripheral blood lymphocytes increased the frequencies of fluorodeoxyuridine-induced fragile sites in a dose-related manner. However, the cells from 30 atomic bomb survivors exposed to either high or low radiation doses 47 years earlier showed no demonstrable difference in fragile site expression, indicating that fragile site induction was ephemeral in nature. When fragile sites were analyzed on the basis of tobacco smoking habits, an elevated number was observed in the smokers. The results confirm that fragile sites can be affected by recent exposure to exogenous agents, but the effect is probably of limited duration, based on the atomic bomb survivor experience. PMID- 7885373 TI - Increased frequencies of micronuclei in T8 lymphocytes of smokers. AB - Micronucleus frequencies and mitotic indices were analyzed in B, T4, and T8 lymphocytes from 40 smokers and 42 non-smoking referents. The highest level of micronuclei was found in T4 cells followed by T8 and B cells. These differences were statistically significant. There were statistically significant linear correlations between the micronucleus frequencies of all three subsets. There was a statistically significant effect of smoking only in the T8 cells. Smoking also increased the number of neutrophilic granulocytes and lymphocytes in the peripheral blood. There was a statistically significant effect of age on the micronucleus frequencies in T4 and T8 lymphocytes. The mitotic indices did not have any effect on the micronucleus frequencies and they were not influenced by smoking, age or sex. PMID- 7885374 TI - Sister-chromatid exchange inducing effect of smokeless tobacco using on T lymphocyte chromosomes. AB - A kind of a smokeless tobacco (Maras powder) is widely used instead of cigarettes in the South Eastern region of Turkey. In this study we investigated the sister chromatid exchange (SCE) inducing effect of this powder on the chromosomes of its users compared with smokers and nonsmokers using standard cell culture methods and SCE staining techniques. Average SCE per metaphase and total SCEs increased significantly among both smokeless tobacco users and smokers compared to nonsmokers (p < 0.01). However, the effect is significantly lower in smokeless tobacco users than in smokers (p < 0.05). PMID- 7885375 TI - Antimutagenicity of an acetone extract of yogurt. AB - Reconstituted non-fat dry milk powder, fermented by a mixture of Streptococcus thermophilus CH3 and Lactobacillus bulgaricus 191R to produce yogurt, was freeze dried and extracted in acetone. After evaporation of the acetone, the extract was dissolved in dimethyl sulfoxide (DMSO) and tested for antimutagenicity. In the Ames test, significant dose-dependent activity was observed against N-methyl-N' nitro-N-nitrosoguanidine (MNNG), 4-nitro-quinoline-N-oxide (4NQO), 3,2'-dimethyl 4-aminobiphenyl (DMAB), 9,10-dimethyl-1,2-benz[a]anthracene (DMBA), and 3-amino-1 methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2). Weak activity was observed against 1,2,7,8-diepoxyoctane (DEO), and no activity was observed against methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), or aflatoxin B1 (AFB1). In a related assay (Saccharomyces cerevisiae D7), significant antimutagenic activity was detected against MNNG and 4NQO. Activity against the experimental colon carcinogens MNNG and DMAB was examined further, as assayed in the Ames test (Salmonella typhimurium TA100). Compounds responsible for both activities were less soluble in aqueous solutions than in DMSO. Adjustment of yogurt pH to 3, 7.6, or 13 prior to freeze-drying and acetone extraction did not significantly alter the amount of anti-MNNG activity recovered. In contrast, extractability of anti-DMAB activity was significantly greater at acidic pH. Conjugated linoleic acid, a known dairy anticarcinogen, failed to inhibit mutagenesis caused by either mutagen, suggesting that other yogurt-derived compound(s) are responsible. Unfermented milk was treated with lactic acid, yogurt bacteria without subsequent growth, or both, to determine if formation of antimutagenic activity required bacterial growth. Extracts of the milk treatments exhibited the same weak antimutagenicity observed in unfermented milk, approximately 2.5-fold less than in the yogurt extracts, suggesting that antimutagenic activity is associated with bacterial growth. PMID- 7885376 TI - Cytogenetic response to asbestos fibers in cultured human primary mesothelial cells from 10 different donors. AB - The ability of amosite asbestos fibers to induce chromosomal aberrations in human primary mesothelial cells obtained from pleural effusions of 10 noncancerous patients was investigated. The glutathione S-transferase M1 (GSTM1) genotypes of the patients were determined, since the GSTM1 null genotype has been associated with increased susceptibility to lung cancer and chemically induced cytogenetic damage. Four of the patients represented the GSTM1 null genotype, and six the GSTM1 positive genotype. Successful chromosome aberration analyses were obtained from six cases, three of them with the GSTM1 null genotype. The level of aberrant cells in unexposed cultures ranged from 2.0% to 7.5%. Statistically significant increases (2.3-3.0-fold compared to controls) in the number of aberrant cells were observed in two cases only: in one case treated with 1 microgram/cm2 of amosite, and in another treated with 2 micrograms/cm2 of amosite. Cell cultures from four individuals showed minor or no increases in the numbers of aberrant cells in the doses tested (1 and 2 micrograms/cm2). Chromosome breaks were the major type of aberration. The amosite exposed cells with significantly increased aberrations were from patients with GSTM1 positive genotypes. Two cases that showed no cytogenetic response to asbestos fibers were of the GSTM1 null genotype. Thus, our results suggest that the lack of the GSTM1 gene does not render human mesothelial cells more susceptible to chromosomal damage induced by asbestos. GSTM1 null cells appeared, however, to be more sensitive to the growth inhibitory effects of asbestos than did GSTM1 positive cells. Variation in the cytogenetic response of human primary mesothelial cells to asbestos fibers was observed to exist, but the fibers do not appear to be potent inducers of structural chromosomal aberrations in these cells. It remains to be established whether individual sensitivity to asbestos fibers, due to specific genetic traits, exists. PMID- 7885377 TI - Effect of renutrition on the proliferation kinetics of PHA stimulated lymphocytes from malnourished children. AB - The fraction of lymphocytes that responded to phytohemagglutinin (PHA) stimulation and initiated cellular proliferation (stimulation index or SI) was determined in groups of healthy and severely malnourished children. SI was determined again in the latter group after a period of nutritional recovery. The proportion of interphasic cells showing PHA response was assessed adding bromodeoxyuridine to the culture, so proliferative nuclei appear big and stain light blue, with dispersed granular chromatin and apparent nucleoli, while non proliferative nuclei look small, stain red, and have compact and homogeneous chromatin. In mitotic nuclei, differential staining of sister chromatids made it possible to distinguish cells that had gone through one, two and three or more proliferation cycles. Based on the data obtained from interphase nuclei and mitosis, the SI was estimated at 48 and 72 h of culture. SI were higher in lymphocytes from healthy children than in those from children with severe malnutrition, even after the period of nutritional recovery. However, the SI was significantly higher in lymphocytes from malnourished children after nutritional recovery. Although in these children more cells are stimulated, there seems to be still damage that causes a cycling delay. PMID- 7885378 TI - Sister-chromatid exchanges in lymphocytes of workers at a phosphate fertilizer factory. AB - The frequencies of sister-chromatid exchange (SCE) in peripheral blood lymphocytes of 40 workers at a phosphate fertilizer factory in North China were studied. HF and SiF4 are main air pollutants in the factory, there is also some dust containing fluoride, phosphate fog, NH3 and SO2. It was shown that the chemicals caused an increase in SCE, and also induced cell mitotic delays. The mean SCEs/cell of the workers and the non-exposed controls were 7.47 +/- 0.31 and 4.94 +/- 0.14 (p < 0.01) respectively. SCEs/cell in 75% of 40 workers were higher than 6 while 40 controls all had values lower than 6. SCE frequencies of the workers increased with length of the chemical exposure period up to 10 years. Smoking enhanced the SCE frequencies induced by the chemicals. PMID- 7885379 TI - Optimal experimental design and sample size for the statistical evaluation of data from somatic mutation and recombination tests (SMART) in Drosophila. AB - In genetic toxicology it is important to know whether chemicals should be regarded as clearly hazardous or whether they can be considered sufficiently safe, which latter would be the case from the genotoxicologist's view if their genotoxic effects are nil or at least significantly below a predefined minimal effect level. A previously presented statistical decision procedure which allows one to make precisely this distinction is now extended to the question of how optimal experimental sample size can be determined in advance for genotoxicity experiments using the somatic mutation and recombination tests (SMART) of Drosophila. Optimally, the statistical tests should have high power to minimise the chance for statistically inconclusive results. Based on the normal test, the statistical principles are explained, and in an application to the wing spot assay, it is shown how the practitioner can proceed to optimise sample size to achieve numerically satisfactory conditions for statistical testing. The somatic genotoxicity assays of Drosophila are in principle based on somatic spots (mutant clones) that are recovered in variable numbers on individual flies. The underlying frequency distributions are expected to be of the Poisson type. However, some care seems indicated with respect to this latter assumption, because pooling of data over individuals, sexes, and experiments, for sample, can (but need not) lead to data which are overdispersed, i.e., the data may show more variability than theoretically expected. It is an undesired effect of overdispersion that in comparisons of pooled totals it can lead to statistical testing which is too liberal, because overall it yields too many seemingly significant results. If individual variability considered alone is not in contradiction with Poisson expectation, however, experimental planning can help to minimise the undesired effects of overdispersion on statistical testing of pooled totals. The rule for the practice is to avoid disproportionate sampling. It is recalled that for optimal power in statistical testing, it is preferable to use equal total numbers of flies in the control and treated series. Statistical tests which are based on Poisson expectations are too liberal if there is overdispersion in the data due to excess individual variability. In this case we propose to use the U test as a non-parametric two-sample test and to adjust the estimated optimal sample size according to (i) the overdispersion observed in a large historical control and (ii) the relative efficiency of the U test in comparison to the t test and related parametric tests. PMID- 7885380 TI - Six mutagenicity assays in exposure biomonitoring of patients receiving carbamazepine for epilepsy or trigeminal neuralgia. AB - The mutagenic potential of carbamazepine (CBZ) therapy has been studied in 37 patients undergoing long-term treatment with this drug. Of the total group, 23 patients suffered from epilepsy and 14 from trigeminal neuralgia. Thirty-one healty subjects served as controls. Six mutagenicity assays with different end points were performed. The possible cytogenetic alterations were evaluated by analyzing sister-chromatid exchange frequencies (SCE), chromosome aberrations (CA), micronuclei (MN), proliferation indices (PRI), and mitotic indices. The Salmonella assay with and without microsomal activation served to measure urinary mutagenicity. The results show that CBZ leads to an increase in SCE (p < 0.01) and PRI (p < 0.05) but had no effect on the other cytogenetic parameters. CBZ was negative in the urine mutagenicity test. Plasma levels of total CBZ, free CBZ and CBZ-10,11-epoxide did not correlate with the cytogenetic alterations. Even though folic acid and gamma-glutamyltranspeptidase were significantly different in patients and controls, there was no significant association between these values and SCE or PRI. Patients with epilepsy and those with trigeminal neuralgia did not differ with respect to the end-points analyzed. PMID- 7885381 TI - DNA repair comes of age. PMID- 7885382 TI - Gene specific DNA repair of damage induced in familial Alzheimer disease cells by ultraviolet irradiation or by nitrogen mustard. AB - We have measured gene specific DNA repair in a normal human fibroblast cell line, and in fibroblast lines from two patients with familial Alzheimer disease (AD). Cells were treated with either ultraviolet radiation (UV) or the chemotherapeutic alkylating agent, nitrogen mustard (HN2). DNA damage formation and repair were studied in the active dihydrofolate reductase (DHFR) gene for the main lesions introduced by each of these two types of DNA damaging agents. The gene specific repair of UV induced cyclobutane pyrimidine dimers in the human DHFR gene was 86% complete in the AD cells after 24 h of repair incubation. This repair efficiency was similar to what we and others have found in normal human fibroblasts. After treatment of the AD cells with HN2, we found the frequency of HN2 induced lesions in the DHFR gene to be similar to the frequency in the transcriptionally inactive delta-globin gene. The gene specific repair of HN2 induced lesions in the DHFR gene was completed within 8-24 h in the normal fibroblast line and in the familial AD line, and the repair kinetics were similar for both cell lines. These results indicate that familial AD fibroblasts have normal gene specific repair of both UV induced and HN2 induced DNA damage in active genes. PMID- 7885383 TI - The concepts of tail moment and tail inertia in the single cell gel electrophoresis assay. AB - Single cell gel electrophoresis under alkaline conditions is a technique used to detect primary DNA damage in individual mammalian cells. Cells embedded in agarose on microscope slides are subjected to lysis, unwinding of DNA and electrophoresis at high pH. After staining with a fluorescent dye, cells with DNA damage display increased migration of genetic material from the cell nucleus. The damage is quantified by measuring the displacement between the genetic material of the nucleus ('comet head') and the resulting 'tail'. The torsional moment of the tail ('tail moment') has been suggested to be an appropriate index of induced DNA damage in considering both the migration of the genetic material as well as the relative amount of DNA in the tail. In the present paper it will be shown that the moment of inertia ('tail inertia'), a not previously described tail parameter, provides a more precise description of the distribution of individual DNA fragments within the tails. The tail inertia was also found to be the most sensitive indicator of the DNA damage induced in peripheral lymphocytes from mice given a single intraperitoneal injection of cyclophosphamide (150 mg/kg b.w.). It is concluded that the tail inertia is an important complement to other tail parameters when looking for damage of DNA with the single cell gel electrophoresis assay. PMID- 7885384 TI - Expression of the human MGMT O6-methylguanine DNA methyltransferase gene in a yeast alkylation-sensitive mutant: its effects on both exogenous and endogenous DNA alkylation damage. AB - Common Mer- cell lines deficient in O6-methylguanine DNA methyltransferase (MTase) activity probably result from the down-regulation of, rather than mutations in, the MGMT gene. However, the down-regulation of other unrelated genes was also observed in some of these cell lines, making it difficult to determine the precise functions of the MGMT MTase gene. To study the biological function of human MGMT MTase, we seek to utilize a newly created yeast mgt1 mutant deficient in the DNA repair MTase activity. The human MGMT cDNA was cloned into yeast expression vectors so that the MGMT gene is under the control of either an inducible GAL1 promoter or a constitutive ADH1 promoter. Upon galactose induction, the PGAL1-MGMT transformant had about 40-fold MTase activity compared to the wild-type strain. MGMT overexpression protected the yeast mgt1 mutant against alkylation-induced killing and mutation. Limited expression of the MGMT gene in the mgt1 mutant still provides significant alkylation resistance, albeit at a reduced level. The yeast mgt1 mutants increase spontaneous mutation rate, whereas constitutive expression of the MGMT gene lowered the spontaneous mutation rate in the mgt1 mutant to the wild-type level. We suggest that MGMT MTase may play the same role in human cells as the MGT1 MTase in yeast cells. Thus our results demonstrate that the human MGMT gene functionally complements the yeast MTase-deficient mutant in the protection against exogenous and endogenous DNA alkylation damage, which provides a useful tool for the study of in vivo mammalian MTase functions. PMID- 7885385 TI - Mutations of a shuttle vector plasmid, pZ189, in Escherichia coli induced by boron neutron captured beam (BNCB) containing alpha-particles. AB - A shuttle vector, pZ189, carrying a bacterial suppressor tRNA marker gene (supF) was dissolved in Tris-EDTA buffer containing 0.3 M 10B-enriched boric acid and then irradiated with boron neutron captured beam (BNCB) produced by the nuclear reaction 10B (n,alpha) 7Li with thermal neutrons. A DNA repair-deficient mutant, KS46 (uvrA-), of Escherichia coli was transformed with the plasmid DNA, and the transformants carrying mutations on the supF gene were selected as nalidixic acid resistant colonies. The mutation frequency (2.4 x 10(-4)) of pZ189 at the D10 dose was about 70 times greater than the spontaneous rate (3.5 x 10(-6)). The plasmid mutations were analyzed using DNA sequencers; 88% of them were base substitutions. A few minus-one frameshifts (7%) and deletions (5%) were detected. Among these base substitutions, transversions of G:C to T:A (42%) and G:C to C:G (29%) predominated. Twenty-seven percent of the base substitutions were G:C to A:T transitions; no A:T to G:C transitions were detected. PMID- 7885386 TI - Induction of double-strand breaks in Chinese hamster ovary cells at two different dose rates of gamma-irradiation. AB - Using pulsed-field gel electrophoresis (PFGE) analysis we investigated the existence of a dose rate effect of gamma-irradiation on the measured presence of DNA double-strand breaks (DSB) in a repair competent (K1) and a repair deficient (mutant xrs6) Chinese hamster ovary (CHO) cell line. The fraction of DNA fragments released from cells embedded in agarose during PFGE after gamma irradiation was taken as a measure of DSB induction. In CHO-K1 cells DSB were present at a significantly higher rate when gamma-irradiation was delivered at a high dose rate of 22 Gy/min (HDR) than at a medium dose rate of 0.45 Gy/min (MDR) at 37 degrees C. However, the same amount of DSB was found when irradiation was performed at the two dose rates at 4 degrees C. The DSB yield was also identical at both dose rates in the DSB repair deficient mutant xrs6. The results indicate that there is an apparent dose rate effect for gamma-ray induced DSB in repair competent CHO cells due to partial repair of DSB taking place during gamma-ray exposures at MDR but not at HDR. This repair of DSB was inhibited upon irradiation at 4 degrees C and in repair deficient xrs6 cells. PMID- 7885387 TI - Different regulation of p53 stability in UV-irradiated normal and DNA repair deficient human cells. AB - The stabilization of p53 protein was studied after UV exposure of normal human skin fibroblasts and cells derived from patients suffering from xeroderma pigmentosum (XP) and trichothiodystrophy (TTD). The data show that p53 is transiently stabilized both in UV-irradiated normal and repair deficient cells. However, particularly at later times after UV irradiation, stabilization of p53 persists much longer in repair deficient XP and TTD cells than in normal cells. The stabilization of p53 was found to be dose-dependent in normal and XP cells. These results indicate that unremoved DNA damage could possibly be responsible for the induction of transient stabilization of p53. PMID- 7885388 TI - Preferential repair of the transcribed DNA strand in the dihydrofolate reductase gene throughout the cell cycle in UV-irradiated human cells. AB - We examined repair of UV-induced cyclobutane pyrimidine dimers (CPD) in each strand of the expressed dihydrofolate reductase gene in human cells in different phases of the cell cycle: G1, early S, middle S, late S, and G2/M. After 4 h of incubation, repair of the transcribed strand was substantially more efficient than repair of the non-transcribed strand in all phases. Furthermore, we observed no remarkable cell cycle-dependent differences in either the initial lesion frequency or the efficiency of repair of the transcribed strand. We conclude that transcription coupled repair operates generally and with high efficiency throughout the cell cycle. PMID- 7885390 TI - Mutagenicity and toxicity of water extracts from the Sora river area. AB - The present study was conducted on the waters of the Sora river and effluents entering to the river. The samples were extracted with XAD-2 resin at different pH and tested for mutagenicity with the modified Ames test using strains S. typhimurium TA98 and TA100. The majority of the mutagenic activity of the samples was found in the neutral pH fraction of the extracts. Strain TA98 in the presence of metabolic activation was the most sensitive condition of mutagenicity. Of the eleven sample extracts, six were positive; neutral fractions of the effluent from wastewater treatment plant, the water leaching from the municipal dump, the water from the lake lying beneath the dump and the untreated effluent, and acid fractions of two samples taken directly from the river. The water leaching from the municipal dump was also mutagenic and toxic without previous extraction. Mutagenic responses before and after extraction of this sample indicate that components responsible for mutagenicity were partly extracted in the neutral fraction. The toxicity of water samples and extracts was tested with Microtox assay, and acid fractions of the extracts were more toxic than the neutral fractions. Comparing the toxicity to the mutagenicity data indicates that components responsible for toxic and mutagenic response were at least partly separated between acid and neutral fraction respectively. PMID- 7885389 TI - The effects of hydrogen peroxide on DNA repair activities. AB - Oxygen free radicals generated by H2O2 are involved in the multistage carcinogenic process; mechanisms include carcinogen activation, oxidative DNA damage, and tumor promotion. In this study, we have evaluated another potential mechanism of H2O2 in carcinogenesis--modulation of DNA repair activities. Preexposure of human peripheral mononuclear leukocytes to H2O2 significantly inhibited DNA repair activities in response to damage induced by N-methyl-N' nitro-N-nitrosoguanidine, measured as unscheduled DNA synthesis. The responses to H2O2 were compared in four healthy human subjects with two sample preparations on different days. Results from multivariate general linear models showed that H2O2 significantly inhibited DNA repair in a dose-dependent manner after adjustment for between- and within-subject variabilities. There was an estimate of 5.0 units (dpm/5 x 10(5) cells) decrease in induced unscheduled DNA synthesis per unit (microM) increase of H2O2 treatment. Furthermore, there was substantial variability in DNA repair activities for the same individual sampled on different days regardless of H2O2 dose level. Results from this study suggest that H2O2 not only can induce DNA damage, but also have suppressive effects on DNA repair. PMID- 7885391 TI - DNA damage in nurses handling antineoplastic agents. AB - In 91 nurses from several divisions of four hospitals in Germany the genotoxic effect caused by the occupational exposure presumably due to mixing of antineoplastic agents was investigated. The amount of DNA single strand breaks and alkali labile sites in the peripheral mononuclear blood cells of the nurses was measured using the alkaline elution method. In ten nurses handling antineoplastic agents not using recommended safety precautions such as safety hoods, gloves or surgical masks a 50% higher level of DNA strand breaks and alkali-labile sites (p < 0.005; U-test) was detected compared to 54 controls. After applying recommended safety precautions a statistically significant decrease (p < 0.01) in the level of DNA strand breaks to the level of controls was observed. In other nurses handling antineoplastic agents by using adequate safety equipment no significantly different amount of DNA strand breaks compared to that of controls was detected. No significant correlation between the level of DNA strand breaks and the weekly contact frequency, the life-time exposure to antineoplastic agents, or the time elapsed since the last handling of the drugs was found in this study. PMID- 7885392 TI - Mutagenicity of O-diazoacetyl-L-serine (azaserine) and 6-diazo-5-oxo-L- norleucine (DON) in a soybean test system. AB - The mutagenicity of O-diazoacetyl-L-serine (azaserine) and 6-diazo-5-oxo-L norleucine (DON), glutamine analogues, were assayed in heterozygous soybean plants (Y11y11), according to the appearance of mutational spots (yellow, dark green and twin) on the leaves. The mutagenicity of azaserine was detected at 0.1 mg/ml, and that of DON, at 0.05 mg/ml. DON was strongly cytotoxic at doses exceeding 0.1 mg/ml. After azaserine and DON treatment, large spots which occupied more than half the leaflet were found in the first and second compound leaves. The glutamine analogues increased the frequency of yellow spots much more than dark green spots or twin spots. Light green spots were observed on y11y11 plants. Azaserine and DON induce somatic crossing over, point mutation and segmental loss as major effects. PMID- 7885393 TI - The suitability of the micronucleus assay in human lymphocytes as a new biomarker of excision repair. AB - The cytokinesis blocked micronucleus assay is relatively insensitive to detect agents that predominantly induce excision repairable DNA lesions. However, it has been recently proposed that excision-repairable DNA lesions induced in G0/G1 phase can be converted to micronuclei by using inhibitors of the gap filling step of excision repair so that unfilled gaps are converted to double stranded breaks after S phase and micronuclei (MN) at completion of mitosis. As it has been recently demonstrated this process could be improved by combining cytosine arabinoside (ARA-C) and hydroxyurea (HU). In the present work, we have investigated the suitability of this new approach by studying its ability to detect excision repairable DNA lesions induced by 10 pesticides (alachlor, atrazine, cypermethrin, deltamethrin, fenpropathrin, fenvalerate, maleic hydrazide, paraquat, permethrin and trifluralin) and 3 well-known mutagenic agents (ethyl methane sulphonate, EMS; methylnitrosourea, MNU; and mytomicin C, MMC). Our results showed that the combination of ARA-C and HU substantially increased the level of MN in whole blood lymphocyte cultures, but it provided an excess of toxicity when further treatments, such as MNU, were performed. When ARA C alone was used, the ARA/CBMN assay appeared to be highly sensitive and specific in detecting agents known to induce excision repairable DNA lesions. Thus, EMS and MNU but not MMC greatly induced DNA excision repair. On the other hand, alachlor, permethrin and, to a lesser extent, trifluralin and fenpropathrin also increased the ratio of excision repairable DNA lesions converted to MN. On the contrary, atrazine, cypermethrin, deltamethrin, fenvalerate, maleic hydrazide and paraquat did not induce excision repair. PMID- 7885394 TI - Genotoxicity of polychlorinated biphenyls (PCBs): recombinogenesis by biotransformation products. AB - A coplanar polychlorinated biphenyl (PCB) when eaten by test animals increased the rate of recombination in somatic cells, indicating a new mechanism of action for these compounds. Using the eye-mosaic test a high bioactivation strain of Drosophila that consumed 4,4'-dichlorobiphenyl (4,4'-DCB) manifested a genotoxicity rate that was three-fold greater than that in animals fed the solvent-spiked medium. This compound was not genotoxic in a suppressed bioactivation strain indicating that genotoxicity requires bioactivation of the compound. High bioactivation test strains made heterozygous for a paracentric inversion, a chromosomal rearrangement that suppresses homologous recombination, exhibited significantly reduced genotoxicity after treatment. PMID- 7885395 TI - The in vivo rat micronucleus test: integration with a 14-day study. AB - A 14-day subchronic toxicity study is routinely conducted in Fischer 344 rats at the Lilly Research Laboratories. This study is done to gather preliminary toxicological information about chemical entities showing efficacy in various pharmacological screens. This manuscript describes the validation of a method for evaluating micronuclei in the bone marrow polychromatic erythrocytes of animals from this test in order to obtain additional information about the genotoxic potential of these compounds without incurring the cost of additional animals or the use of additional test article, which is often in limited supply. Compounds selected for evaluation were acetylsalicylic acid, mitomycin C, cyclophosphamide, colchicine, 6-mercaptopurine, and etoposide. With the exception of colchicine, the results obtained were as expected with acetylsalicylic acid yielding negative results and the other compounds yielding positive results. These findings are consistent with those published for mice (MacGregor et al., Fund. Appl. Toxicol., 14, 513-522, 1990) and show that a bone marrow micronucleus test can be successfully integrated into a routine subchronic rat toxicology study. PMID- 7885396 TI - Cytogenetic studies of stainless steel welders using the tungsten inert gas and metal inert gas methods for welding. AB - Cytogenetic damage was studied in lymphocytes from 23 welders using the Tungsten Inert Gas (TIG), and 21 welders using the Metal Inert Gas (MIG) and/or Metal Active Gas (MAG) methods on stainless steel (SS). A matched reference group I, and a larger reference group II of 94 subjects studied during the same time period, was established for comparison. Whole blood conventional cultures (CC), cultures in which DNA synthesis and repair were inhibited (IC), and the sister chromatid exchange (SCE) assay were applied in the study. For the CC a statistically significant decrease in chromosome breaks and cells with aberrations was found for both TIG/SS and MIG/MAG/SS welders when compared with reference group II. A non-significant decrease was found for the corresponding parameters for the two groups of welders when compared with their matched referents. A statistically significant negative association was found between measurements of total chromium (Cr) in inhaled air and SCE, and a weaker negative correlation with hexavalent Cr (Cr(VI)) in air. In conclusion, no cytogenetic damage was found in welders exposed to the TIG/SS and MIG/MAG/SS welding fumes with low content of Cr and Ni. On the contrary, a decline in the prevalence of chromosomal aberrations was indicated in the TIG/SS and MIG/MAG/SS welders, possibly related to the suggested enhancement of DNA repair capacity at slightly elevated exposures. PMID- 7885397 TI - GeneTox manager for bacterial mutagenicity assays: a personal computer and minicomputer system. AB - GeneTox Manager (GTM) is a data capture, data management, and statistical analysis program used for microbial mutagenicity data. Its main purpose is to provide a homogeneous environment for the collection, organization, and analysis of data generated in the laboratory while also supporting a quality assurance program. The complete system consists of both a personal computer (PC) system and a minicomputer (VAX) system. The joint PC/VAX version of the system is designed to function with both the PC and VAX FOCUS databases so that the VAX can be used for long-term storage, archiving of files, and the analysis of large groups of data. Because of the highly specialized use and nature of the PC/VAX version, this discussion is focused upon the PC stand-alone version. The user-friendly system uses a structured menu system, screen entry helps, and other help screens. GTM provides tabular and graphical summaries of the data and performs specialized statistical analyses. This public domain software was written primarily using Clipper. The manuals and programs are now available through the government's National Technical Information Service. PMID- 7885398 TI - Mutagenicity of benzo[a]pyrene and dibenzopyrenes in the Salmonella typhimurium TM677 and the MCL-5 human cell forward mutation assays. AB - The mutagenicity of benzo[a]pyrene (B[a]P), dibenzo[ae]pyrene (DB[ae]P), dibenzo[ah]pyrene (DB[ah]P), dibenzo[ai]pyrene (DB[ai]P), and dibenzo[al]pyrene (DB[al]P) was measured in quantitative forward mutation assays with bacteria (Salmonella typhimurium TM677) and a metabolically competent cell line derived from human B-lymphoblastoid cells (MCL-5) that contained activity for five cytochrome P450s and microsomal epoxide hydrolase found in human liver. DB[al]P and B[a]P, both potent animal carcinogens, were the most mutagenic substances in both assays. DB[al]P was nearly 50-fold more potent than B[a]P in human cells, but only 60% more mutagenic in Salmonella. The carcinogenic isomer DB[ah]P, though nonmutagenic in bacteria, was active in human cells. The following mutagenic potency series, expressed as the minimum detectable mutagen concentration (MDMC) in nmol/ml, was obtained with Salmonella in the presence of rat liver postmitochondrial supernatant (PMS): DB[al]P (3.7), B[a]P (5.8), DB[ae]P (6.9), DB[ai]P (14.9), DB[ah]P (> 100). None of the compounds were mutagenic in the absence of PMS. In human MCL-5 cells the potency series was: DB[al]P (3.1 x 10(-4)), B[a]P (1.5 x 10(-2)), DB[ae]P (2.5 x 10(-2)), DB[ah]P (0.5), DB[ai]P (3.2). The human cell assay thus exhibited over a 10,000-fold range between the most mutagenic and least mutagenic compound, whereas in the bacterial assay there was only a corresponding four-fold difference if the nonmutagenic DB[ah]P was excluded. The results were discussed in terms of their concordance with animal carcinogenicity studies. PMID- 7885399 TI - DNA damage in mononuclear blood cells of metal workers exposed to N nitrosodiethanolamine in synthetic cutting fluids. AB - In 28 smoking and 37 non-smoking male metal workers from 7 small to medium sized plants the genotoxic effect caused by the occupational exposure measured as DNA single strand breaks in the peripheral mononuclear blood cells was investigated. Metal workers using synthetic cutting fluids are possibly exposed to the carcinogenic N-nitrosodiethanolamine (NDELA). In this investigation NDELA was detected in the air of the working halls in a concentration up to 1000 ng/m3 and in the cutting fluids in a concentration up to 135 mg/l (mean values per plant). Workers staying in rooms with a mean concentration of NDELA in the air of about 1 microgram/m3 revealed two times more DNA strand breaks than workers staying in an environment with less than 50 ng/m3 of NDELA (p < 0.01). Non-smoking workers with more than 4.5 h contact to cutting fluids per day showed an 1.5 times higher mean level of DNA strand breaks than their nonsmoking colleagues having had less than 4.5 h contact to cutting fluids (p < 0.02). Also workers having had work place related complaints showed a statistically significantly higher level of DNA strand breaks compared to workers with no or no work place-related complaints. No significant correlation was obtained between the extent of DNA damage and the estimated extent of skin contact or the concentration of NDELA found in the cutting fluids. Therefore, for workers in this investigation NDELA incorporated by inhalation is probably more relevant for genotoxic damage than NDELA resorbed by skin. An increased level of DNA damage was found in metal workers depending on the concentration of NDELA in the air of the work places. However, without further investigations it cannot be excluded that also other concomitant agents in the environment were responsible for the observed genotoxic effect. PMID- 7885400 TI - G2 phase repair of X-ray-induced chromosomal DNA damage in trichothiodystrophy cells. AB - The repair of X-ray-induced DNA damage during G2 cell-cycle phase has been examined in lines of skin fibroblasts from three patients with trichothiodystrophy (TTD), one with apparently normal and two with defective nucleotide excision repair (NER). These responses are compared with those of five lines from clinically normal controls, lines from xeroderma pigmentosum (XP), Cockayne syndrome (CS), Down syndrome (DS), and ataxia telangiectasia (AT) patients. Chromosomal DNA repair was measured as the chromatid aberration frequency (CAF) or total number of chromatid breaks and long gaps per 100 metaphase cells, determined 0.5-1.5 h after X-irradiation (53 rad). Chromatid breaks and gaps (as defined herein) represent unrepaired DNA strand breaks. Only one of the TTD lines, TTD 1BR, showed an abnormally high CAF. This line was shown subsequently to be of a different complementation group, representing a new nucleotide excision repair gene. An abnormally high CAF was also observed, as reported previously, in XP-C, AT and DS but not in CS skin fibroblasts. In addition, cell lines were examined for DNA incision activity by an indirect method in which chromatid aberrations were enumerated with or without ara-C, an inhibitor of repair synthesis, added after X-irradiation. All TTD lines had abnormally low incision activity. PMID- 7885401 TI - Gene amplification in Chinese hamster DNA repair deficient mutants. AB - In order to study the possible relationship between gene amplification and DNA repair we analyzed the amplification of the CAD gene in four mutants hypersensitive to UV light (CHO43RO, CHO7PV, UV5 and UV61) isolated in vitro from Chinese hamster cell lines (CHO-K1 and AA8). These mutants are characterized by different defects in the nucleotide excision repair mechanism and represent complementation groups 1, 9, 2, and 6 respectively. To evaluate the amplification ability of each cell line we measured the rate of appearance of PALA resistant clones with the Luria and Delbruck fluctuation test. Resistance to PALA is mainly due to amplification of the CAD gene. In the mutants CHO43RO, UV5 and CHO7PV we reproducibly found an amplification rate lower than in the parental cell lines (2 5 times), while in UV61 the amplification rate was about 4 times higher. This result indicates that each mutant is characterized by a specific amplification ability and that the unefficient removal of UV induced DNA damage can be associated with either a higher or a lower amplification rate. However, the analysis of randomly isolated CHO-K1 clones with normal UV sensitivity has shown variability in their amplification ability, making it difficult to relate the specific amplification ability of the mutants to the DNA repair defect and suggesting clonal heterogeneity of the parental population. PMID- 7885402 TI - Antimutagenicity of eugenol in the rodent bone marrow micronucleus test. AB - The antimutagenic effect of eugenol on the mutagenicity of cyclophosphamide (CP), mitomycin C (MMC), ethyl methanesulfonate (EMS) and benzo[a]pyrene (B[a]P) was assessed in the rodent bone marrow micronucleus test using male Swiss mice. Oral administration of eugenol (0.4% in the diet) for 15 days was found to decrease significantly the frequency of micronucleated polychromatic erythrocytes (MPEs) elevated by CP. No effect was found on the frequency of MPEs elevated by MMC, EMS and B[a]P. The results provide some support for antimutagenic potency of eugenol in vivo. PMID- 7885403 TI - Mathematical parameters for quantification of mutational responses in bacteria. AB - This paper introduces a new parameter, derivable from dose-response data for induced mutagenesis in bacteria, that can be used to quantify mutational responses in short-term tests. We called this parameter the mutational response of the bipartite experimental system (agent plus cells). We defined it as being jointly proportional to the efficiency of the mutagen and the sensitivity of the test. We show how this quantity can be used to rank order chemical carcinogens on the basis of their mutagenicity and to determine the strength of any quantitative correlation that may exist between mutagenicity in bacteria and carcinogenicity in rodents. We find that this particular measure of mutational response for 10 direct-acting monofunctional alkylating agents correlates remarkably well with the rodent carcinogenicity of these chemicals measured in terms of their reciprocal TD50 values. PMID- 7885404 TI - The relative radiosensitivity of TK6 and WI-L2-NS lymphoblastoid cells derived from a common source is primarily determined by their p53 mutational status. AB - The lymphoblastoid cell lines WI-L2-NS and TK6 were derived from a non-clonal pool of cells taken from a human spleen. Despite their common background they exhibit marked differences in radiosensitivities; D0 values of 93 and 67 cGy have been reported for WI-L2-NS and TK6 cells respectively. We show here that this differential radiosensitivity is due to a decreased ability of the WI-L2-NS cell line to undergo radiation-induced apoptosis. Further, the WI-L2-NS cell line overexpresses the p53 gene product as a result of a mutation in codon 237 of the p53 gene. These data indicate that WI-L2-NS cells through disruption of normal p53 function are unable to engage the radiation-induced apoptosis program and so are relatively radioresistant. PMID- 7885405 TI - Mutagenic activity of 6-aminoquinoxalines in Salmonella typhimurium. AB - Mutagenicity of 6-aminoquinoxaline derivatives was tested with Salmonella typhimurium strains TA98 and TA100 in the presence and absence of S9 mix from the viewpoint that the 6-aminoquinoxaline skeleton is a common unit of mutagenic imidazoquinoxalines. We tested nine compounds: 5-methyl-6-methylaminoquinoxaline (1), 3,5-dimethyl-6-methylaminoquinoxaline (2), 2,5-dimethyl-6 methylaminoquinoxaline (3), 6-methylamino-2,3,5-trimethylquinoxaline (4), 2,3 diethyl-5-methyl-6-methylaminoquinoxaline (5), 5-methyl-6-methylamino 3 phenylquinoxaline (6), 6-amino-2,3,5-trimethylquinoxaline (7), 6-dimethylamino 2,3,5- trimethylaminoquinoxaline (8), 6-amino-2,3-dimethylquinoxaline (9). These compounds showed the mutagenic activity for both TA98 and TA100 in the presence of S9 mix, where they were more sensitive for TA100 strain. Methyl groups at the 2, 3 and/or 5 positions increased the potency of mutagenicity (1 < 2 < 3 << 4, 9 < 7). However, ethyl groups at the 2 and 3 positions lowered the mutagenicity of the methyl substitute but elevated it of the parental compound (1 < 5 < 4). A methyl group at the N6 position decreased the mutagenicity (7 > 4 > 8). PMID- 7885407 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 11-1995. A 39-year-old man with chronic renal failure, aortic regurgitation, and a calcified mass around the aortic root. PMID- 7885406 TI - Paclitaxel (taxol) PMID- 7885408 TI - Fish and heart disease. PMID- 7885409 TI - Answers to the antiphospholipid-antibody syndrome? PMID- 7885410 TI - Health care for elderly persons--myths and realities. PMID- 7885411 TI - Hypertensive crisis since FDR--a partial victory. PMID- 7885412 TI - Drug promotion. PMID- 7885413 TI - Drug promotion. PMID- 7885414 TI - Drug promotion. PMID- 7885415 TI - Drug promotion. PMID- 7885416 TI - Drug promotion. PMID- 7885417 TI - Accidental hypothermia. PMID- 7885418 TI - Accidental hypothermia. PMID- 7885419 TI - Accidental hypothermia. PMID- 7885420 TI - Prevention of radiocontrast-induced renal insufficiency. PMID- 7885421 TI - Prevention of radiocontrast-induced renal insufficiency. PMID- 7885422 TI - Nitric oxide-induced motor neuron disease in a patient with alcoholism. PMID- 7885423 TI - Medicare reimbursement for intravenous vancomycin at home. PMID- 7885424 TI - This day 50 years ago. PMID- 7885425 TI - Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. AB - BACKGROUND: It has been hypothesized that a diet containing n-3 fatty acids from fish reduces the risk of coronary heart disease, but few large epidemiologic studies have examined this question. METHODS: In 1986, 44,895 male health professionals, 40 to 75 years of age, who were free of known cardiovascular disease completed detailed and validated dietary questionnaires as part of the Health Professionals Follow-up Study. During six years of follow-up, we documented 1543 coronary events in this group: 264 deaths from coronary disease, 547 nonfatal myocardial infarctions, and 732 coronary-artery bypass or angioplasty procedures. RESULTS: After controlling for age and several coronary risk factors, we observed no significant associations between dietary intake of n 3 fatty acids or fish intake and the risk of coronary disease. For men in the top fifth of the group in terms of intake of n-3 fatty acids (median, 0.58 g per day), the multivariate relative risk of coronary heart disease was 1.12 (95 percent confidence interval, 0.96 to 1.31), as compared with the men in the bottom fifth (median, 0.07 g per day). For men who consumed six or more servings of fish per week, as compared with those who consumed one serving per month or less, the multivariate relative risk of coronary disease was 1.14 (95 percent confidence interval, 0.86 to 1.51). The risk of death due to coronary disease among men who ate any amount of fish, as compared with those who ate no fish, was 0.74 (95 percent confidence interval, 0.44 to 1.23), but the risk did not decrease as fish consumption increased. CONCLUSIONS: Although the possibility of residual confounding by unmeasured factors cannot be entirely excluded, these data suggest that increasing fish intake from one to two servings per week to five to six servings per week does not substantially reduce the risk of coronary heart disease among men who are initially free of cardiovascular disease. PMID- 7885426 TI - Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. AB - BACKGROUND: Medical termination of pregnancy can be successfully performed with a combination of mifepristone (RU 486) and a prostaglandin analogue. We conducted a prospective, randomized trial to compare oral with vaginal administration of the prostaglandin E1 analogue misoprostol for first-trimester abortion in women treated initially with mifepristone. METHODS: The study population consisted of 270 women seeking abortion within 63 days after the onset of amenorrhea. The dose of mifepristone was 600 mg, and the dose of misoprostol was 800 micrograms. The study had two primary end points: expulsion of the conceptus without the need for a surgical procedure, and abortion within four hours after the administration of misoprostol. RESULTS: Expulsion of the conceptus without the need for a surgical procedure occurred in 95 percent of the women who received misoprostol vaginally and in 87 percent of those who received it orally (P = 0.03). The rate of continued pregnancy was 7 percent with the oral regimen and 1 percent with the vaginal regimen (P = 0.01). Ninety-three percent of the women receiving misoprostol vaginally had abortions within four hours, as compared with only 78 percent of the women receiving the drug orally (P < 0.001). Vomiting and diarrhea were reported more frequently by the women who received oral misoprostol than by those who received vaginal misoprostol (P = 0.04 and P = 0.002, respectively). CONCLUSIONS: After the administration of mifepristone, vaginal administration of misoprostol is more effective and better tolerated than oral administration for the induction of first-trimester abortion. PMID- 7885427 TI - Transdermal nicotine as maintenance therapy for ulcerative colitis. AB - BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Having found previously that treatment with transdermal nicotine patches and mesalamine (5 aminosalicylic acid) has a beneficial effect on active colitis, we examined the value of transdermal nicotine for the maintenance of remission. METHODS: We treated 80 patients with ulcerative colitis in remission with either transdermal nicotine or placebo patches for six months in a randomized, double-blind study. Incremental doses of nicotine were given for the first three weeks to achieve a maintenance dose; most patients tolerated 15 mg for 16 hours daily. All patients were taking mesalamine preparations as maintenance treatment at entry into the study; this treatment was stopped once the maintenance dose of nicotine was achieved. Clinical, sigmoidoscopic, and histologic assessments were made at the beginning and the end of the study, or at relapse. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study. RESULTS: There was no significant difference in the number of relapses between the groups. Twenty-two patients in the nicotine group were prematurely withdrawn from the study, 14 because of relapse and 8 for other reasons, including side effects and protocol violations. In the placebo group, 20 patients were withdrawn prematurely, 17 because of relapse and 3 for other reasons. Among patients using 15-mg nicotine patches, serum nicotine and cotinine concentrations were lower than expected and may reflect poor compliance. Side effects were reported by 35 patients--21 in the nicotine group and 14 in the placebo group--the most common of which were nausea, lightheadedness, and itching. CONCLUSIONS: Transdermal nicotine alone was no better than placebo in the maintenance of remission of ulcerative colitis, and premature withdrawal due to side effects was more common in the nicotine group. PMID- 7885428 TI - The management of thrombosis in the antiphospholipid-antibody syndrome. AB - BACKGROUND: The antiphospholipid-antibody syndrome is a thrombophilic disorder in which venous or arterial thrombosis, or both, may occur in patients with antiphospholipid antibodies. The optimal treatment of these patients is unclear. We assessed the efficacy of warfarin, low-dose aspirin, or both in the secondary prevention of thrombosis in patients with the syndrome. METHODS: One hundred forty-seven patients (124 [84 percent] of whom were female) with the antiphospholipid-antibody syndrome and a history of thrombosis were studied retrospectively. The syndrome was primary in 62 patients and was associated with systemic lupus erythematosus in 66 patients and lupus-like disease in 19. Each patient's history was reviewed. RESULTS: One hundred one patients (69 percent) had a total of 186 recurrences of thrombosis. The median time between the initial thrombosis and the first recurrence was 12 months (range, 0.5 to 144 months). Treatment with high-intensity warfarin (producing an international normalized ratio of > or = 3) with or without low-dose aspirin (75 mg per day) was significantly more effective (P < 0.001 by the log-rank test) than treatment with low-intensity warfarin (producing an international normalized ratio of < 3) with or without low-dose aspirin or treatment with aspirin alone in preventing further thrombotic events (recurrence rates per patient-year, 0.013, 0.23, and 0.18, respectively). The rate of recurrence of thrombosis was highest (1.30 per patient year) during the first six months after the cessation of warfarin therapy. Complications involving bleeding occurred in 29 patients during warfarin therapy and were severe in 7 (0.071 and 0.017 occurrence per patient-year, respectively). CONCLUSIONS: The risk of recurrent thrombosis in patients with the antiphospholipid-antibody syndrome is high. Long-term anticoagulation therapy in which the international normalized ratio is maintained at or above 3 is advisable in these patients. PMID- 7885429 TI - Images in clinical medicine. Spontaneous atheroembolism. PMID- 7885430 TI - Longevity and Medicare expenditures. AB - BACKGROUND: In the United States, the elderly account for over one third of health care spending. The total population over the age of 65 is projected to increase, as is life expectancy beyond the age of 65. We studied current patterns of Medicare expenses according to age at death and the possible effect of future demographic changes on Medicare spending. METHODS: We used data from the Medicare program to estimate lifetime Medicare expenses for a sample of 129,166 beneficiaries, 65 or older, who died in 1989 and 1990, according to age at death. Spending for nursing home care not covered by Medicare was excluded. (Nursing home costs represent about 20 percent of total health care spending for the elderly and increase with age.) Through simulation, we assessed the lifetime payments by Medicare for enrollees who turned 65 in 1990 and those who will do so in 2020. RESULTS: Estimated lifetime Medicare payments (in 1990 dollars) ranged from $13,044 for persons who died at 65 years of age, to $56,094 for those who died at 80, to $65,633 for those who died at 101 or older. The payments associated with an additional year of life and the average annual payments over an enrolle's lifetime both decreased as the age at death increased. The estimated 7.9 percent increase in life expectancy beyond 65 years that will have taken place between 1990 and 2020 (19.1 years past the age of 65 in 2020, as compared with 17.7 years in 1990) was associated with an estimated increase of 2.0 percent in lifetime Medicare payments. Of the estimated $98 billion increase in total lifetime payments (in 1990 dollars) from the 1990 group to the 2020 group, 74.3 percent was due to the larger size of the original birth cohort who will reach the age of 65 in 2020, 22.5 percent to an increase in the proportion of that birth cohort projected to survive to 65 years of age, and 3.2 percent to improved life expectancy beyond 65. CONCLUSIONS: The effect on Medicare spending of increased longevity beyond the age of 65 may not be great. Total Medicare payments will be more substantially affected by the expected increase in the absolute number of elderly people. PMID- 7885431 TI - Gene therapy approval may be rocky road for industry. PMID- 7885432 TI - Medical centre cuts staff in preparation for 'managed care'. PMID- 7885434 TI - Prospective studies urged of health risks. PMID- 7885433 TI - US sets up new bioethics advisory board. PMID- 7885435 TI - France seeks to tighten its control over life sciences. PMID- 7885436 TI - Gravity scores one, microgravity zero. PMID- 7885437 TI - The use of Taxol as a trademark. PMID- 7885438 TI - Space science. Destructive debris. PMID- 7885439 TI - Drug receptors. Inverse agonists exposed. PMID- 7885440 TI - Developmental biology. Growth factor lends a hand. PMID- 7885441 TI - Proton movement on membranes. PMID- 7885442 TI - The major evolutionary transitions. AB - There is no theoretical reason to expect evolutionary lineages to increase in complexity with time, and no empirical evidence that they do so. Nevertheless, eukaryotic cells are more complex than prokaryotic ones, animals and plants are more complex than protists, and so on. This increase in complexity may have been achieved as a result of a series of major evolutionary transitions. These involved changes in the way information is stored and transmitted. PMID- 7885443 TI - Tidal effects of disconnected hydrocarbon seas on Titan. AB - Thermodynamic and photochemical arguments suggest that Titan, the largest satellite of Saturn, has a deep ocean of liquid hydrocarbons. At visible wavelengths, Titan's surface is obscured by a thick stratospheric haze, but radar observations have revealed large regions of high surface reflectivity that are inconsistent with a global hydrocarbon ocean. Titan's surface has also been imaged at infrared wavelengths, and the highest-resolution data (obtained by the Hubble Space Telescope) show clear variations in surface albedo and/or topography. The natural interpretation of these observations is that Titan, like the Earth, has continents and oceans. But Titan's high orbital eccentricity poses a problem for this interpretation, as the effects of oceanic tidal friction would have circularized Titan's orbit for most configurations of oceans and continents. Here we argue that a more realistic topography, in which liquid hydrocarbons are confined to a number of disconnected seas or crater lakes, may satisfy both the dynamical and observational constraints. PMID- 7885444 TI - Aberrant differentiation of neuromuscular junctions in mice lacking s laminin/laminin beta 2. AB - Synapse formation requires a complex interchange of information between the pre- and postsynaptic partners. At the skeletal neuromuscular junction, some of this information is contained in the basal lamina (BL), which runs through the synaptic cleft between the motor nerve terminal and the muscle fibre. During regeneration following injury, components of synaptic BL can trigger several features of postsynaptic differentiation in the absence of the nerve terminal, and of presynaptic differentiation in the absence of the muscle fibre. One nerve derived component of synaptic BL, agrin, is known to affect postsynaptic differentiation, but no muscle-derived components have yet been shown to influence motor nerve terminals. A candidate for such a role is s-laminin (also called laminin beta 2), a homologue of the B1 (beta 1) chain of the widely distributed BL glycoprotein, laminin. s-Laminin is synthesized by muscle cells and concentrated in synaptic BL. In vitro, recombinant s-laminin fragments are selectively adhesive for motor neuron-like cells, inhibit neurite outgrowth promoted by other matrix molecules, and act as a 'stop signal' for growing neurites. By generating and characterizing mice with a targeted mutation of the s laminin gene, we show here that s-laminin regulates formation of motor nerve terminals. PMID- 7885445 TI - Nitric oxide mediates activity-dependent synaptic suppression at developing neuromuscular synapses. AB - Temporal correlation between pre- and postsynaptic activities is an important mechanism that regulates synaptic connectivity during development and synaptic plasticity in the adult. In developing neuromuscular junctions, postsynaptic activity is critical in functional suppression and, ultimately, elimination of the synapses. Although repetitive postsynaptic firing asynchronous to the presynaptic activity results in a persistent synaptic suppression, the underlying molecular mechanism remains unknown. Here we provide evidence that nitric oxide (NO), a free radical implicated in several forms of synaptic plasticity, may serve as a retrograde signal for activity-dependent suppression in the neuromuscular synapse. NO donors and activators of the cyclic GMP pathway suppressed spontaneous and evoked synaptic currents. Moreover, the synaptic suppression induced by repetitive postsynaptic depolarization was prevented by the NO-binding protein haemoglobin and by inhibitors of NO synthase. Thus, synaptic suppression may be triggered by NO released from a postsynaptic myocyte that fires asynchronously to the presynaptic terminal. PMID- 7885446 TI - Control of lamprey locomotor neurons by colocalized monoamine transmitters. AB - Neurons in the central nervous system (CNS) often store more than one neurotransmitter, but as yet the functional significance of this type of coexistence is poorly understood. 5-Hydroxytryptamine (5-HT) modulates calcium dependent K+ channels (KCa) responsible for the postspike afterhyperpolarization in different regions of the CNS. In lamprey, 5-HT neurons control apamine sensitive KCa channels in spinal locomotor network interneurons, thereby in addition regulating the duration of locomotor bursts. We report here that these spinal 5-HT neurons also contain dopamine. Like 5-HT, dopamine causes a reduction of the afterhyperpolarization, but in this case it is due to a reduction of calcium entry during the action potential, which results in a reduced activation of KCa. 5-HT and dopamine are both released from these midline neurons, and both reduce the afterhyperpolarization through two distinctly different, but complementary cellular mechanisms. The net effect of dopamine (10-100 microM) on the locomotor network is similar to that of 5-HT, and the effects of dopamine and 5-HT are additive at the network level. PMID- 7885447 TI - Malarial haemozoin/beta-haematin supports haem polymerization in the absence of protein. AB - Malarial parasites growing inside erythrocytes digest up to 80% of the host cell's haemoglobin within a lysosomal organelle, the digestive vacuole. They sequester the potentially toxic haem (Fe (II) protohaematoporphyrin) that is released during this process into an insoluble pigment called haemozoin, which consists of polymerized Fe (III) protohaematoporphyrin subunits. We have studied this process of haem polymerization, which was previously reported to be enzyme mediated and the target of the quinoline antimalarial drugs chloroquine and quinine. Here we show that, rather than being enzyme-mediated, haem polymerization is actually a chemical process, dependent only on the presence of haem-derived material associated with haemozoin and not on protein. This discovery does not invalidate haem polymerization as a target for drug intervention and the mechanism by which haemozoin formation is initiated is still not understood, but our view of this process and of the action of choroquine must be reconsidered. PMID- 7885448 TI - Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the beta 2-adrenoceptor. AB - G-protein-coupled receptors are thought to have an inactive conformation (R), requiring an agonist-induced conformational change for receptor/G-protein coupling. But new evidence suggests a two-state model in which receptors are in equilibrium between the inactive conformation (R), and a spontaneously active conformation (R*) that can couple to G protein in the absence of ligand (Fig. 1). Classic agonists have a high affinity for R* and increase the concentration of R*, whereas inverse agonists have a high affinity for R and decrease the concentration of R*. Neutral competitive antagonists have equal affinity for R and R* and do not displace the equilibrium, but can competitively antagonize the effects both of agonists and of inverse agonists. The lack of suitable in vivo model systems has restricted the evidence for the existence of inverse agonists to computer simulations and in vitro systems. We have used a transgenic mouse model in which there is such marked myocardial overexpression of beta 2 adrenoceptors that a significant population of spontaneously activated receptor (R*) is present, inducing a maximal response without agonist. We show that the beta 2-adrenoceptor ligand ICI-118,551 functions as an inverse agonist, providing evidence supporting the existence of inverse agonists and validating the two state model of G-protein-coupled receptor activation. PMID- 7885449 TI - Replication of transcriptionally active chromatin. AB - In eukaryotic cells, active genes and their regulatory sequences are organized into open chromatin conformations in which nucleosomes can be modified, disrupted or totally absent. It has been proposed that these characteristic chromatin structures and their associated factors might be directly inherited by the newly synthesized daughter strands during chromosome duplication. Here we show that in the yeast Saccharomyces cerevisiae, replication machinery entering upstream of a transcriptionally active ribosomal RNA gene generates two newly replicated coding regions regularly packaged into nucleosomes, indicating that the active chromatin structure cannot be directly inherited at the replication fork. Whereas the establishment of an exposed chromatin conformation at some newly replicated rRNA gene promoters can occur shortly after the passage of the replication fork, regeneration of the active chromatin structure along the coding region is always a post-replicative process involving disruption of preformed nucleosomes. PMID- 7885450 TI - Association of Cdk-activating kinase subunits with transcription factor TFIIH. AB - The RNA polymerase II large subunit contains an essential carboxy-terminal domain (CTD) believed to be involved in the response to regulators during transcription initiation. The CTD is phosphorylated on a portion of RNA polymerase II molecules in vivo and it can be phosphorylated by the general transcription factor TFIIH in vitro. A highly purified TFIIH from rat liver has been described; this, like human and yeast TFIIH, contains associated CTD kinase and helicase activities. We report here that two polypeptides of the purified mammalian TFIIH are the MO15/Cdk7 kinase and cyclin H subunits of the Cdk-activating kinase Cak, previously identified as a positive regulator of Cdc2 and Cdk2. TFIIH and Cak preparations are each capable of phosphorylating recombinant CTD and recombinant Cdk2 proteins. The presence of Cak in TFIIH indicates that Cak may have roles in transcriptional regulation and in cell-cycle control. PMID- 7885451 TI - Glaxo and Wellcome. PMID- 7885452 TI - Maddox to step down from editor's chair at Nature. PMID- 7885453 TI - NIH to review priorities in readiness for future cuts... PMID- 7885454 TI - Grant challenges role of peer review in an age of e-mail. PMID- 7885455 TI - France joins Italy in mouse gene store bid. PMID- 7885456 TI - Wellcome pledges $80 million for population studies. PMID- 7885458 TI - Italy widens peer review of health research. PMID- 7885457 TI - Europe extends biotech grants 'experiment'. PMID- 7885459 TI - UK virology institute 'to change direction'. PMID- 7885460 TI - When life begins. PMID- 7885461 TI - Questionnaires and copyright. PMID- 7885462 TI - Questionnaires and copyright. PMID- 7885463 TI - The hidden science of eugenics. AB - The early eugenicists were not stupid, but they did not share our social values. The rise and fall of the eugenics movement is a history that modern medical geneticists would do well to heed. PMID- 7885465 TI - Population genetics. The cheetah controversy. PMID- 7885464 TI - Cell-cell recognition. Zipping together a cell adhesion interface. PMID- 7885466 TI - Developmental biology. Angles on activin's absence. PMID- 7885467 TI - Artefact or network evolution? PMID- 7885468 TI - Knockout mouse fault lines. PMID- 7885469 TI - Early AGEing and Alzheimer's. PMID- 7885470 TI - The consequences of imperfect mixing in autocatalytic chemical and biological systems. AB - When chemical reactions whose rate increases with the concentration of a product species are carried out in imperfectly mixed systems, a variety of complex behaviours can occur. These phenomena, which have relevance for biological processes as well, include chaotic and stochastic behaviour and selection of one final state over an equally probable alternative. PMID- 7885471 TI - Structural basis of cell-cell adhesion by cadherins. AB - Crystal structures of the amino-terminal domain of N-cadherin provide a picture at the atomic level of a specific adhesive contact between cells. A repeated set of dimer interfaces is common to the structure in three lattices. These interactions combine to form a linear zipper of molecules that mirrors the linear structure of the intracellular filaments with which cadherins associate. This cell-adhesion zipper may provide a mechanism to marshal individual molecular adhesive interactions into strong bonds between cells. PMID- 7885472 TI - Dorsalizing signal Wnt-7a required for normal polarity of D-V and A-P axes of mouse limb. AB - Formation of the vertebrate limb requires specification of cell position along three axes. Proximal-distal identity is regulated by the apical ectodermal ridge (AER) at the distal tip of the growing limb. Anterior-posterior identity is controlled by signals from the zone of polarizing activity (ZPA) within the posterior limb mesenchyme. Dorsal-ventral identity is regulated by ectodermally derived signals. Recent studies have begun to identify signalling molecules that may mediate these patterning activities. Members of the fibroblast growth factor (FGF) family are expressed in the AER and can mimic its proximal-distal signalling activity. Similarly, the gene Sonic hedgehog (Shh) is expressed in the ZPA, and Shh-expressing cells, like ZPA cells, can cause digit duplications when transplanted to the anterior limb margin. In contrast, no signal has yet been identified for the dorsal-ventral axis, although Wnt-7a is expressed in the dorsal ectoderm, suggesting that it may play such a role. To test this possibility, we have generated mice lacking Wnt-7a activity. The limb mesoderm of these mice shows dorsal-to-ventral transformations of cell fate, indicating that Wnt-7a is a dorsalizing signal. Many mutant mice also lack posterior digits, demonstrating that Wnt-7a is also required for anterior-posterior patterning. We propose that normal limb development requires interactions between the signalling systems for these two axes. PMID- 7885473 TI - Functional analysis of activins during mammalian development. AB - Activins are dimeric (beta A beta A; beta B beta B; beta A beta B) members of the transforming growth factor-beta superfamily. They are widely expressed during murine development, are highly conserved during vertebrate evolution, and may be involved in mesoderm induction and neurulation in Xenopus laevis and Oryzias latipes. To investigate the function of mammalian activins in vivo, we generated mice with mutations either in activin-beta A or in both activin-beta A and activin-beta B. Activin-beta A-deficient mice develop to term but die within 24 h of birth. They lack whiskers and lower incisors and have defects in their secondary palates, including cleft palate, demonstrating that activin-beta A must have a role during craniofacial development. Mice lacking both activin subunits show the defects of both individual mutants but no additional defects, indicating that there is no functional redundancy between these proteins during embryogenesis. In contrast to observations in lower vertebrates, zygotic expression of activins is not essential for mesoderm formation in mice. PMID- 7885474 TI - Different phenotypes for mice deficient in either activins or activin receptor type II. AB - Activins are believed to initiate a signal transduction cascade by binding to serine/threonine kinase receptors types I and II. Activins bind to several different receptors in vitro, but the significance of this interaction in vivo has not been confirmed. To test the function of the type II activin receptor (ActRcII) in mammalian development and reproduction, we generated a null mutation in the ActRcII gene in mice using embryonic stem cell technology. We expected ActRcII-deficient mice to phenocopy activin-deficient mice. A few ActRcII deficient mice had skeletal and facial abnormalities reminiscent of the Pierre Robin syndrome in humans, but most lacked these defects and developed into adults; their follicle-stimulating hormone was suppressed, and their reproductive performance was defective. These findings confirm a role of ActRcII in activin signalling in pituitary gonadotrophs. The striking lack of overlap between phenotypes of ActRcII-deficient and activin-deficient mice suggests that the ligands that signal through ActRcII during embryonic development are not activins. PMID- 7885475 TI - Multiple defects and perinatal death in mice deficient in follistatin. AB - Follistatin, an activin-binding protein and activin antagonist in vitro, can bind to heparan sulphate proteoglycans and may function in vivo to present activins to their receptors. In the mouse, follistatin messenger RNA is first detected in the deciduum (on embryonic day 5.5), and later in the developing hindbrain, somites, vibrissae, teeth, epidermis and muscle. In Xenopus laevis, overexpression of follistatin leads to induction of neural tissue. Here we use loss-of-function mutant mice to investigate the function of follistatin in mammals. We find that follistatin-deficient mice are retarded in their growth, have decreased mass of the diaphragm and intercostal muscles, shiny taut skin, skeletal defects of the hard palate and the thirteenth pair of ribs, their whisker and tooth development is abnormal, they fail to breathe, and die within hours of birth. These defects are more widespread than those seen in activin-deficient mutant mice, indicating that follistatin may modulate the actions of several members of the transforming growth factor-beta family. PMID- 7885476 TI - The product of hedgehog autoproteolytic cleavage active in local and long-range signalling. AB - The secreted protein products of the hedgehog (hh) gene family are associated with local and long-range signalling activities that are responsible for developmental patterning in multiple systems, including Drosophila embryonic and larval tissues and vertebrate neural tube, limbs and somites. In a process that is critical for full biological activity, the hedgehog protein (Hh) undergoes autoproteolysis to generate two biochemically distinct products, an 18K amino terminal fragment, N, and a 25K carboxy-terminal fragment, C (ref. 16); mutations that block autoproteolysis impair Hh function. We have identified the site of autoproteolytic cleavage and find that it is broadly conserved throughout the hedgehog family. Knowing the site of cleavage, we were able to test the function of the N and C cleavage products in Drosophila assays. We show here that the N product is the active species in both local and long-range signalling. Consistent with this, all twelve mapped hedgehog mutations either affected the structure of the N product directly or otherwise blocked the release of N from the Hh precursor as a result of deletion or alteration of sequences in the C domain. PMID- 7885477 TI - Neural progenitor cell engraftment corrects lysosomal storage throughout the MPS VII mouse brain. AB - Many metabolic diseases affecting the central nervous system are refractory to treatment because the blood-brain barrier restricts entry of therapeutic molecules. It may be possible to deliver therapeutic gene products directly to the brain by transplantation of neural progenitor cells, which can integrate into the murine central nervous system in a cytoarchitecturally appropriate manner. We tested this approach in mucopolysaccharidosis VII (Sly disease), a lysosomal storage disorder of humans, dogs and mice caused by an inherited deficiency of beta-glucuronidase. Lysosomal accumulation of glycosaminoglycans occurs in the brain and other tissues, causing a fatal progressive degenerative disorder, including mental retardation. Treatments are designed to provide a source of normal enzyme for uptake by diseased cells. We report here that by transplanting beta-glucuronidase-expressing neural progenitors into the cerebral ventricles of newborn mice, donor cells engrafted throughout the neuraxis. At maturity, donor derived cells were present as normal constituents of diverse brain regions. beta Glucuronidase activity was expressed along the entire neuraxis, resulting in widespread correction of lysosomal storage in neurons and glia in affected mice. PMID- 7885478 TI - DNA-bend modulation in a repressor-to-activator switching mechanism. AB - Recent discoveries of activator proteins that distort DNA but bear no obvious activation domains have focused attention on the role of DNA structure in transcriptional regulation. Here we describe how the transcription factor MerR can mediate repression as well as activation through stereospecific modulation of DNA structure. The repressor form of MerR binds between the -10 and -35 promoter elements of the bacterial mercury-detoxification genes, PT, allowing RNA polymerase to form an inactive complex with PT and MerR at this stress-inducible promoter. Upon mercuric ion binding, Hg-MerR converts this polymerase complex into the transcriptionally active or 'open' form. We show here that MerR bends DNA towards itself in a manner similar to the bacterial catabolite-activator protein CAP, namely at two loci demarked by DNase I sensitivity, and that the activator conformation, Hg-MeR, relaxes these bends. This activator-induced unbending, when coupled with the previously described untwisting of the operator, remodels the promoter and makes it a better template for the poised polymerase. PMID- 7885479 TI - Structure of a multisubunit complex that promotes DNA branch migration. AB - The RuvA and RuvB proteins of Escherichia coli, which are induced in response to DNA damage, are important in the formation of heteroduplex DNA during genetic recombination and related recombinational repair processes. In vitro studies show that RuvA binds Holiday junctions and acts as a specificity factor that targets the RuvB ATPase, a hexameric ring protein, to the junction. Together, RuvA and RuvB promote branch migration, an ATP-dependent reaction that increases the length of the heteroduplex DNA. Electron microscopic visualization of RuvAB now provides a new insight into the mechanism of this process. We observe the formation of a tripartite protein complex in which RuvA binds the crossover and is sandwiched between two hexameric rings of RuvB. The Holliday junction within this complex adopts a square-planar structure. We propose a molecular model for branch migration, a unique feature of which is the role played by the two oppositely oriented RuvB ring motors. PMID- 7885480 TI - Crystal structure of the nuclear Ras-related protein Ran in its GDP-bound form. AB - The Ran proteins constitute a distinct branch of the superfamily of Ras-related GTP-binding proteins which function as molecular switches cycling between GTP bound 'on' and GDP-bound 'off' states. Ran is located predominantly in the nucleus of eukaryotic cells and is involved in the nuclear import of proteins as well as in control of DNA synthesis and of cell-cycle progression. We report here the crystal structure at 2.3 A resolution of human Ran (Mr 24K) complexed with GDP and Mg2+. This structure reveals a similarity with the Ras core (G-domain) but with significant variations in regions involved in GDP and Mg2+ coordination (switch I and switch II regions in Ras), suggesting that there could be major conformational changes upon GTP binding. In addition to the G-domain, an extended chain and an alpha-helix were identified at the carboxy terminus. The amino terminal (amino-acid residues MAAQGEP) stretch and the acidic tail (DEDDDL) appear to be flexible in the crystal structure. PMID- 7885481 TI - Structure and function of the multifunctional DNA-repair enzyme exonuclease III. AB - The repair of DNA requires the removal of abasic sites, which are constantly generated in vivo both spontaneously and by enzymatic removal of uracil, and of bases damaged by active oxygen species, alkylating agents and ionizing radiation. The major apurinic/apyrimidinic (AP) DNA-repair endonuclease in Escherichia coli is the multifunctional enzyme exonuclease III, which also exhibits 3'-repair diesterase, 3'-->5' exonuclease, 3'-phosphomonoesterase and ribonuclease activities. We report here the 1.7 A resolution crystal structure of exonuclease III which reveals a 2-fold symmetric, four-layered alpha beta fold with similarities to both deoxyribonuclease I and RNase H. In the ternary complex determined at 2.6 A resolution, Mn2+ and dCMP bind to exonuclease III at one end of the alpha beta-sandwich, in a region dominated by positive electrostatic potential. Residues conserved among AP endonucleases from bacteria to man cluster within this active site and appear to participate in phosphate-bond cleavage at AP sites through a nucleophilic attack facilitated by a single bound metal ion. PMID- 7885483 TI - Skate to where the puck is going to be. PMID- 7885482 TI - Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA. AB - The protein p21 (WAF1, CIP1 or sdi1), induced by the tumour-suppressor protein p53, interacts with and inhibits two different targets essential for cell-cycle progression. One of these is the cyclin-Cdk family of kinases and the other is the essential DNA replication factor, proliferating-cell nuclear antigen (PCNA). We report here that separate domains of p21 are responsible for interacting with and inhibiting the two targets. An amino-terminal domain inhibits cyclin-Cdk kinases and a carboxy-terminal domain inhibits PCNA. Using these separated domains, we have determined that p21 inhibits different biological systems through different targets. The PCNA-binding domain is sufficient for inhibition of DNA replication based on simian virus 40, whereas the Cdk2-binding domain is sufficient for inhibition of DNA replication based on Xenopus egg extract and for growth suppression in transformed human cells. PMID- 7885484 TI - An interview with Donna J. Denniston. Interview by Connie R Curran. AB - Donna J. Denniston, MA, RN, is health care executive education director, Johnson & Johnson Hospital Services, Inc., Piscataway, NJ. Ms. Denniston manages the health care industry programs for key customer groups including the Johnson & Johnson-Wharton Fellows Program in Management for Nurse Executives. In this interview, she discusses the program's goals and accomplishments, as well as the important career and leadership issues facing nurse executives today. PMID- 7885485 TI - The Johnson & Johnson-Wharton Fellows Program Experience. PMID- 7885486 TI - Effects of the partners in care practice model on nursing outcomes. AB - The purpose of this study was to identify the effects of an empirically-designed nursing practice model on the outcome variables of job satisfaction, autonomy, and retention/turnover of nursing staff. After 6 months significant differences were found on the experimental unit in overall job satisfaction, and on the subscales of job satisfaction in task requirements and perception of pay. Significant differences were found between the control and experimental unit on the Job Satisfaction Index subscales of interaction, task requirements, and autonomy. No significant differences were found in retention/turnover of staff between the experimental and control unit. PMID- 7885487 TI - Price controls, health care reform, and new RN shortages. PMID- 7885489 TI - Blueprint for integrating nurse extenders in critical care. AB - As more and more hospitals use the techniques of work restructuring to reduce their operating budget, no nursing department can escape change. Intensive care units can effectively and economically change skill mix by using a design that incorporates essential staff input and a structured educational program. Implementing a Patient Care Specialty Technician role in critical care serves as a driving force to control costs while maintaining quality care and patient satisfaction. PMID- 7885488 TI - Environmental uncertainty: implications for practice model redesign. AB - Analysis of one academic medical center revealed three distinct nursing practice environments distinguished by increasing levels of complexity, change, unpredictability, and uncertainty. Designing practice models to accommodate these conditions will facilitate more efficient and effective patient outcomes. PMID- 7885490 TI - Outcomes of a pneumonia critical path. AB - Research outcomes of a pneumonia critical path for 73 patients in a metropolitan New York City hospital were analyzed. The positive outcomes included a decreased length of stay, decreased hospital charges, and improved multidisciplinary documentation. PMID- 7885491 TI - Nurse managers, managed care, and the external/outward view: a critical success factor. PMID- 7885493 TI - Competing in the new job market: Part I--Your resume. PMID- 7885492 TI - Health care reform and the 103rd Congress: the final chapter. PMID- 7885494 TI - Work restructuring: the process of redefining roles of patient caregivers. AB - Redefining roles of patient caregivers as an element of work restructuring is essential to maintain and/or enhance an organization's efficiency in this competitive health care environment. This process works best when all levels and disciplines within the organization are involved and when meshed with senior management's leadership and vision. PMID- 7885495 TI - Congrette syndrome. PMID- 7885496 TI - [Retrobulbar hemorrhage]. PMID- 7885497 TI - [Observations in the measurement of Ph in the esophagus for the diagnosis of gastroesophageal reflux in children]. PMID- 7885498 TI - [Gastroesophageal reflux in infants; recommendations for diagnosis and treatment]. PMID- 7885499 TI - [Multidisciplinary team treatment of children with a congenital disorders of the upper extremity]. PMID- 7885500 TI - [With maintaining equilibrium: experimental study of the limits of acceleration which the human body can endure without losing postural balance]. AB - OBJECTIVE: To explore the limits of acceleration to which a human organism can be exposed without loss of postural balance. DESIGN: Experimental study. SETTING: TNO Human Factors Research Institute, Soesterberg, and the public transport, Amsterdam. METHOD: Volunteers underwent accelerations of the underground in the laboratory. The acceleration that could be tolerated without extra support, was under investigation. In this way, conditions could be determined that cause loss of postural balance. RESULTS: A comparison of data obtained in the laboratory with measurements during public transportation proved that in tram, bus and tube, the 'jerk' and the level of acceleration are both in principle unmanageable without extra support. CONCLUSION: A built-in limitation of the jerk component in vehicles of the public transport could offer a substantial contribution to solving the problem of loss of postural balance by the passengers. PMID- 7885501 TI - [10-year follow-up after surgery for colon cancer: no further mortality from cancer after 7 years]. AB - OBJECTIVE: To evaluate the 10-year follow-up of a cohort of 141 patients operated between 1979 and 1981, and to analyse the prognostic significance of traditional tumour parameters, using a univariate and a multivariate analysis. DESIGN: Prospective descriptive study. SETTING: Department of Surgery, University Hospital Maastricht, the Netherlands. METHODS: In 1979 a database was established in which 141 consecutive patients with colorectal carcinoma were included. The 5 year and 10-year survival rates were determined and the values of the clinicopathological staging (deducted from the Dukes classification), CEA expression, tumour size, localisation of the tumour and age of the patient as tumour markers were assessed. RESULTS: The 5-year and 10-year survival rates were 30.5% and 15.6% respectively. The Dukes staging system appeared to be the most important prognostic factor for survival (p = 0.0004), but tumour size and shape, and central lymph node involvement were independent prognostic factors. Furthermore, no patients died as a result of colon tumour after 7 years of follow up. CONCLUSIONS: The Dukes staging system is the most important prognostic factor for survival. The follow-up of patients treated for colon carcinoma can be stopped after seven years. Only polyp surveillance should be continued after this time. PMID- 7885502 TI - [Adjuvant postoperative radiotherapy in patients with endometrial carcinoma; no effect on length of survival in retrospective study in the Southeastern Netherlands]. AB - OBJECTIVE: To assess the use of postoperative radiotherapy in patients with adenocarcinoma of the endometrium. DESIGN: Retrospective study. SETTING: Catharina Hospital Eindhoven, the Netherlands. METHOD: An assessment was made of referral, survival in relation to patient factors and postoperative radiotherapy treatment, in 422 patients registered in the Eindhoven Cancer Registry between January 1975 and December 1984 with carcinoma of the endometrium. RESULTS: Half the patients (54%) were referred for postoperative radiotherapy, patients over 70 years old less frequently (p = 0.004), patients with deeply infiltrating tumours (p < 0.001) or tumours with poor grade of differentiation (p = 0.03) more frequently. The referral percentages varied between 36% for patients with well differentiated superficial tumours and 83% for patients with poorly differentiated tumours with deep infiltration. Age, postoperative tumour stage and depth of infiltration for patients under 60 showed a statistically significant association with overall survival. A benefit from postoperative radiotherapy with respect to survival could not be established. CONCLUSION: It appears that the variation in referral is also due to differences of opinion concerning appropriate treatment between the referring gynaecologists. This study did not demonstrate a beneficial effect from postoperative radiotherapy. This should be confirmed in a prospective study. PMID- 7885504 TI - [From the library of the Nederlands Tijdschrift voor Geneeskunde; Den Nieuwen Herbarius by Leonhard Fuchs (1501-1566) and the emergence of botany]. PMID- 7885503 TI - [Cyclic neutropenia and treatment with granulocyte colony-stimulating factor (G CSF)]. AB - A patient with familial cyclic neutropenia (CN) is presented. In a son of a mother with known CN, periodic neutropenia was demonstrated a few months after birth. At 18 years of age, the boy had recurrent episodes of cervical lymphadenopathy, complicated by an abscess. Periodic treatment with granulocyte colony stimulating factor (G-CSF) was initiated, and since then, he hardly had any symptoms and clinically showed substantial improvement. Based on in-vitro colony assays of patients with CN, it is nowadays suggested that a disturbance in growth factor receptor binding or post-receptor signal transduction is the cause of this rare benign haematological disorder. PMID- 7885506 TI - [Is influenza vaccination of employees not belonging to risk groups sensible and is this a task for Arbo services?]. PMID- 7885505 TI - [Bungi jumping]. PMID- 7885507 TI - [Fungi which cause onychomycosis in The Netherlands]. PMID- 7885508 TI - [Sleep endocrinology]. AB - Human sleep is characterized by the cyclic occurrence of episodes of non-REM and REM sleep and by distinct secretory patterns of several hormones. During depression and aging there are similar changes in the neurophysiological and the neuroendocrine components of sleep. A review of data deriving from clinical studies in patients and controls and from animal research supports the view of a bidirectional interaction between sleep structure and nocturnal hormone secretion. These data suggest that changes in the activity of neurohormones have a key role in the development of aberrant sleep during depression and during aging. PMID- 7885509 TI - [Suicidal behavior of depressed patients at inpatient admission]. AB - Early recognition of suicidal behavior is of extreme importance for avoidance of this cause of death. The risk of suicide attempts is particularly high in psychiatric illness, and among hospital in-patients especially in those with depression. Thus, the risk of suicide should be estimated in the first interview after admission to a psychiatric hospital. Our study analysed the routine documentation of such interviews on admission to the Psychiatrische Klinik der Freien Universitat in Berlin: 41% of all depressive patients were suicidal. Suicidal and non-suicidal depressive patients could be differentiated by the following traits: suicidal patients were younger, had been younger at the initial onset of depressive illness, had made more suicide attempts in the past, and had a greater number of relatives who had committed suicide or made suicide attempts. They were more often single or divorced, and had fewer children of their own. Their psychopathology was characterized by a more strongly developed syndrome of depression, hostility and apathy. These findings point to a pattern of characteristics that are linked with suicidal behavior, which can be used to estimate the risk of suicide right at the beginning of a stay in hospital. PMID- 7885510 TI - [Neurobiological principles of drug dependence. Exemplified by opioids and psychostimulants]. AB - New insights into the neurobiological mechanisms underlying drug addition have become available with recent advances in experimental research. This is particularly true for the opioids and psychostimulants: behavioural and biochemical studies have revealed that activation of the mesolimbic "reward pathways", involving the release of dopamine, which acts upon D1 receptors, plays a critical part in the development of addictive behaviour. In the case of the opioids, the differentiation of various types of receptors (and of the corresponding endogenous ligands, the endorphins) revealed a bidirectional role of opioid receptors in this process: stimulation of the reward system, mediated by mu- and delta-opioid receptors, and inhibition of the reward pathways, mediated by the activation of chi-receptors. Thus, a functional equilibrium between these tonically active opioidergic systems appears to provide a neutral motivational state. During drug withdrawal, the decrease in dopamine release most probably reflects a disturbance of this equilibrium. There is increasing evidence that endogenous opioidergic mechanisms also modulate addictive behaviour caused by psychostimulants and other drugs of abuse. This article discusses the implications of these new findings in the context of pharmacotherapeutic strategies in the treatment of addictive behaviours. PMID- 7885511 TI - [Munchausen syndrome by proxy]. AB - The term "Munchausen by proxy" denotes a special form of factitious disorder and a rare kind of child abuse. We present the case of a 12-year-old boy, whose mother's manipulations culminated in his immobilization in a wheelchair and the implantation of a pacemaker. Problems of diagnosis and clinical management of Munchausen by proxy are discussed. PMID- 7885512 TI - [What modifies the course of Crohn disease?]. AB - This paper presents empirical results concerning the interdependency of somatic and psychological factors in the course of Crohn's disease. Data derived from the Heidelberg psychosomatic study on Crohn's disease are explored with the help of canonical correlation analysis. Somatic data recorded in the acute stage of Crohn's disease were not empirically found to be predictive of the psychological status after convalescence empirically. On the other hand, we did find psychological data that allowed prediction of the somatic status when the patients were in remission. Of these psychological data, coping resources are the most important predictors of the course of the disease. In particular, depressive forms of coping are correlated with personality factors, whereas active coping forms are not. The results have implications for scientific theory as well as for clinical practice. PMID- 7885513 TI - [Cost-effectiveness of syphilis screening in a clinical for general psychiatry]. AB - The most important clinical picture of syphilis for psychiatry is that of progressive paralysis. It is an organic psychosis with varying psychopathology. Therefore, nearly all patients in psychiatric departments undergo lues screening (TPHA) on admission. A cost-benefit analysis is presented. In the examination period from 1 January 1983 to 30 September 1988, in all 8915 patients were newly admitted to the department of general psychiatry at the University Hospital of Essen: 98 of these patients were TPHA-positive, and 6 patients had to be treated with antibiotics. One patient had neurolues. It seems therefore, that lues screening in a department of general psychiatry is performed for traditional reasons at high cost but with minimal benefit. The 6 patients who underwent a specific therapy were analysed; a catalogue of indication criteria for TPHA screening was elaborated and is presented. PMID- 7885514 TI - [Organic origin of maniform psychosis. A case example of progressive paralysis]. AB - A 36-year-old patient with a highly developed manic-type psychosis is presented. The precise, thorough psychopathological examination indicated organic illness. The diagnosis of neurosyphilis was established when specific CNS-derived immunoglobulin was detected. The existence of increased general inflammatory parameters in the CSF indicated that the condition was active. Treatment with penicillin resulted in clear improvement of laboratory findings, but clinical recovery was only partial. PMID- 7885515 TI - [An increased incidence of megacolon in psychiatric and neurologic patients]. AB - The incidence of megacolon is elevated in neuropsychiatric patients. Siegmund was the first, in 1935, to report on the development of megacolon and megasigmoid as the result of chronic atropine therapy of patients with postencephalitic parkinsonism and the associated risk of stercoraceous ulcers and ileus or even sudden death. The etiology of increased frequency of megacolon among neuropsychiatric patients is assumed to be nonuniform, and to include organic defects of centers of the autonomous nervous system in the diencephalon and/or hypothalamous, pharmacodynamic, psychogenic and neurogenic influences on the autonomic nervous system, akinesia and increased obstipation among psychiatric patients, insufficient pressure in the abdominal wall especially in the mentally retarded, with frequently associated weakness of the connective tissue. In cases of long-term therapy with psychotropic drugs the anticholinergic side effects with the risk of megacolon and resulting ileus, sometimes with fatal outcome should be borne into mind. PMID- 7885516 TI - [Follow-up of Werlhof disease after onset of treatment with maprotiline]. AB - Whereas leucocytopenia is reported to be a relatively frequent side-effect of treatment with tricyclic and tetracyclic antidepressants and atypical neuroleptic agents, isolated thrombocytopenias are rare. To our knowledge there are no reports of thrombocytopenia in connection with the tetracyclic antidepressant maprotiline. This report describes the case of a 53-year-old female patient with neurotic depression and an initially unsuspected chronic idiopathic thrombocytopenic purpura (ITP). Following previous treatment with an angiotensin converting enzyme inhibitor, cilazapril, and an estrogen derivative, the patient developed an episode of the ITP after beginning treatment with maprotiline. The possible aetiology and the course of the illness are discussed. PMID- 7885517 TI - [Abuse of body weight reducing agents in bulimia nervosa]. AB - Abuse of dieting agents is a frequent, but often unrecognized, problem in patients with eating disorders. Especially women suffering from bulimia nervosa tend to abuse diet pills containing amphetamines and laxatives, diuretics, caffeine and emetics. In this review the frequency of substance abuse in bulimic women, the side effects and possible health risks of this abuse are discussed. PMID- 7885518 TI - [A case of rare side effects of certain antidepressive drugs]. AB - Because of a depressive syndrome, a 39-year-old patient received 20 mg fluoxetine per day. Approximately 4 weeks later, treatment with this drug was stopped after the patient had complained of worsening tremor, particularly of the upper extremities. In addition, accommodation difficulties and problems with word finding had appeared shortly before. The symptoms became worse after fluoxetine had been discontinued. Treatment of the side effects with piperiden and bromazepam brought about no real improvement in the patient's condition. The passive tremor with a frequency of approximately eight per second mainly suggests an extrapyramidal-parkinsonian cause. Five weeks after treatment with fluoxetine had been discontinued, owing to the persistence of the depressive syndrome the patient received maprotiline and clomipramine by infusion in a private hospital. After 2-3 days the patient complained of headaches and had a slightly raised temperature. After 7 days maprotiline and clomipramine were discontinued completely. During the fever there was no leucocytosis, so that a drug fever was diagnosed. These rare side effects are discussed. PMID- 7885519 TI - [Folie a deux. Review of the literature and an unusual case]. AB - We present a review of the concept's history and discuss different possible varieties of "folie a deux". Following this we report the case of a couple whose "folie a deux" has lasted for ten years. They have four of their own children and three further children from the husband's first marriage. Of special interest is the personality of the protagonists, their psychological assessment, and the so far ineffective therapeutic interventions that have been undertaken in efforts to save the children. PMID- 7885520 TI - [Differential diagnostic-therapeutic use of Carbamazepine in alcohol withdrawal syndrome]. PMID- 7885521 TI - [Understanding metaphorical speech by healthy and schizophrenic patients]. PMID- 7885522 TI - The ambulatory blood pressure in normotensive and hypertensive subjects: results from an international database. AB - OBJECTIVE: To delineate more precisely an operational threshold for making clinical decisions based on ambulatory blood pressure (ABP) measurement by studying the ABP in subjects who were diagnosed as either normotensive or hypertensive by conventional blood pressure (CBP) measurement. SUBJECTS: Twenty four research groups recruited 7069 subjects. Of these, 4577 were normotensive (systolic CBP < or = 140 mmHg and diastolic CBP < or = 90 mmHg) and 1773 were hypertensive (systolic CBP > or = 160 mmHg and/or diastolic CBP > or = 90 mmHg). Of the latter, 1324 had systolic and 1310 had diastolic hypertension. RESULTS: Ninety-five percent of the normotensive subjects had a 24-h ABP below (systolic and diastolic, respectively) 133 and 82 mmHg. Of the patients with systolic hypertension, 24% had a 24-h systolic ABP of < 133 mmHg. Similarly, 30% of those with diastolic hypertension had a 24-h diastolic ABP of < 82 mmHg. The probability that hypertensive patients had a 24-h ABP below these thresholds was higher in women than in men, increased with age and was 2- to 4-fold greater if the CBP of the patient had been measured at only one visit and if fewer than 3 CBP measurements had been averaged to establish the diagnosis of hypertension. By contrast, for each 10-mmHg increment in systolic CBP, this probability decreased by 54% for the 24-h systolic ABP and by 25% for the 24-h diastolic ABP, and for each 5 mmHg increment in diastolic CBP it increased by 6 and 9%, respectively. CONCLUSION: The ABP distributions of the normotensive subjects included in the present international database were not materially different from those in previous reports in the literature. One-fifth to more than one-third of the hypertensive patients had an ABP which was below the 95th centile of the ABP in normotensive subjects, but this proportion decreased if the hypertensive patients had shown a higher CBP upon repeated measurement. The prognostic implications of elevated CBP in the presence of normal ABP remain to be determined. PMID- 7885523 TI - Osmol and anion gaps in the diagnosis of poisoning. PMID- 7885524 TI - Treatment of patients with IVCS and gross oedema and ascites with diuretic combination and ACE-inhibitors: relation to baseline PRA and PAC. AB - OBJECTIVE: (1) To assess plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in patients with inferior vena cava syndrome (IVCS). (2) To study in an open fashion the efficacy of loop diuretic treatment, single, or in combination with an ACE-inhibitor or with spironolactone. METHODS: In 13 patients PRA and PAC were measured and related to urinary sodium excretion (UNa). RESULTS: Highly elevated PRA and PAC were found in recently developed IVCS. The correlation coefficient between PAC and UNa was -0.61, p < 0.05. In 10 patients the influence of captopril (C)] at maximum tolerable doses with or without furosemide (F) was evaluated. Mean tolerated dose of C amounted to 8.8 mg t.i.d. (range 2-25), achieving a PAC reduction of 26%. Efficacy of F was severely blunted when PAC exceeded the low-normal range. Spironolactone addition at 100 mg/day in non-responders to F or to F and C, induced immediate natriuretic responses except in a patient with 7-70 fold increase in PAC. CONCLUSIONS: (1) In IVCS loop diuretic efficacy is attenuated by aldosterone activation; (2) complete aldosterone suppression with captopril is difficult to achieve due to dose restriction; (3) spironolactone is favoured for a synergistic response. PMID- 7885525 TI - Haematological and biochemical profile of uncomplicated pregnancy in nulliparous women; a longitudinal study. AB - BACKGROUND: Most laboratory parameters change during pregnancy. A serial study of a large number of routine haematological and biochemical blood parameters and biochemical urine parameters was conducted in a group of 66 healthy nulliparous pregnant women, who had an uncomplicated pregnancy. METHODS: Blood samples and 24 h urine samples were obtained at four weeks intervals during pregnancy and at 1 (1P) and 6 (6P) weeks after delivery. RESULTS: During pregnancy, haemoglobin concentration, haematocrit and erythrocyte count were lower, mean cell volume was not different, and mean cell haemoglobin and mean cell haemoglobin concentration were enhanced. The platelet count during pregnancy was not different from the level at 6P but increased 60% at 1P. Serum ferritin decreased 50% whereas plasma fibrinogen increased 100%. Serum creatinine (-28%), uric acid (-35%) and urea ( 40%) concentrations were reduced during pregnancy. The serum concentrations of sodium (-4 mmol/l) and potassium (-0.2 mmol/l) were lower, but serum chloride was unaltered. Serum protein and albumen concentrations declined by 7.8 and 9.4 g/l respectively. The serum concentrations of bilirubin, ALAT, ASAT and gamma-GT remained unaltered. Serum LDH was 30% above normal non-pregnant values at 1P. The heat-stable alkaline phosphatase level increased in the third trimester. Heat stable and heat-labile fractions were both elevated at 1P. The serum osmolality was 9 mosmol/kg lower and urine volume was about 25% higher during pregnancy. The creatinine excretion was unaltered but creatinine clearance increased by 25%. CONCLUSIONS: The concentrations of most components change during pregnancy. The interpretation of results of laboratory tests in pregnant women should be made with caution. PMID- 7885526 TI - Percutaneous gallbladder drainage in emphysematous cholecystitis. AB - Emphysematous cholecystitis is a serious disorder with a high mortality and morbidity. We report successful drainage of the gallbladder in a male diabetic patient with emphysematous cholecystitis in whom surgery was considered contraindicated because of his poor cardiac status. PMID- 7885527 TI - Pancreatic pseudocyst as a cause of upper gastrointestinal bleeding. AB - A 67-year-old man with a history of an attack of pancreatitis was repeatedly investigated for recurrent gastrointestinal bleeding necessitating blood transfusions. Routine investigations did not reveal the source of bleeding. Repeated angiograms also were not diagnostic. A hot spot identified on a 99mTc pertechnate-labelled erythrocyte scan prompted an endoscopic retrograde cholangio pancreatography (ERCP), which showed bleeding through the papilla of Vater. The source of bleeding appeared to be a small pancreatic pseudocyst. The patient was treated with a duodenopancreatectomy in which the pylorus was preserved. No rebleeding occurred since the operation. Pancreatic pseudocysts must be considered as a source of upper gastrointestinal bleeding in patients with bleeding of "obscure" origin. 99mTc-pertechnate-labelled erythrocyte scanning and ERCP may be helpful, even when angiography is normal. PMID- 7885528 TI - Chronic hepatitis caused by lisinopril. AB - ACE inhibitors are used world-wide for treatment of hypertension and cardiac failure; liver damage is a rare but potentially severe side-effect of these drugs. In this case report we describe a patient with chronic liver damage due to lisinopril. PMID- 7885529 TI - Ambulatory blood pressure monitoring in clinical trials with antihypertensive agents. AB - Ambulatory blood pressure monitoring (ABPM) is being used increasingly for the evaluation of antihypertensive agents in clinical trials. In this brief review several aspects of ABPM are discussed. In particular, attention is paid to the extent to which ABPM is subject to a placebo response and the extent to which the sample size of the study population can be reduced with this type of measurement. In addition, some remarks are made with regard to how selection of patients with this methodology can be improved and how it may be used as a tool to evaluate the duration of action of antihypertensive agents. Finally, some potential disadvantages of ABPM as compared to conventional clinic blood pressure measurements are discussed. PMID- 7885530 TI - Hereditary and acquired risk factors for childhood stroke. AB - Forty-four patients aged from one month to 16 years suffering from arterial stroke were carefully studied for any hereditary and acquired risk factors for stroke. No physiologic anticoagulant deficiency or antiphospholipid syndrome was found. Two patients had mitochondrial disease (MELAS). Six patients had migraineous stroke. Migraine and thrombotic disease in the families of the patients were not more prevalent than in the families of the controls. Preceding infections occurred in 34% of the patients, that is, significantly more common than in the age-matched controls. Two children had borreliosis. Repeat strokes occurred particularly in patients with migraine (n = 4) and MELAS (n = 2). The hereditary factors studied here seem to play only a minor role in pediatric patients. Repeated strokes have a varied etiology and are difficult to prevent. Important triggers of strokes are infections. PMID- 7885531 TI - High-intensity proton and T2-weighted MRI signals in the globus pallidus in juvenile-type of dentatorubral and pallidoluysian atrophy. AB - Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder. An expanded CAG trinucleotide repeat sequence motif in a gene on the short arm of chromosome 12 has recently been identified in patients with DRPLA. Juvenile-type DRPLA is characterized by childhood onset and progressive myoclonic epilepsy (PME). According to the pathological study, the degeneration of the globus pallidus is more marked in this than in other types. We observed high-intensity signals in the globus pallidus on proton and T2 weighted magnetic resonance imaging (MRI) in a patient clinically diagnosed as juvenile-type DRPLA who had the expanded CAG trinucleotide repeat motif in the DRPLA gene. The globus pallidus may be affected in the early stages of this type of DRPLA, and MRI may be useful for the early diagnosis of DRPLA. PMID- 7885532 TI - Phenotypic variation and magnetic resonance imaging (MRI) in Salla disease, a free sialic acid storage disorder. AB - Salla disease (SD) is a recessively inherited lysosomal storage disorder particularly common in the Finnish population. Patients with SD are normal at birth, but develop psychomotor delay and ataxia during the first year of life. Phenotypic variation of SD is wide, ranging from severely disabled children to mentally retarded adults capable of living under sheltered conditions. In the present study four unusually severely affected patients were investigated by detailed clinical examination, magnetic resonance imaging (MRI) and analysis of the excretion of free sialic acid in urine. MRI study, reported here for the first time, revealed a similarly defective myelination pattern in seven patients. The myelination process seemed to cessate at the level of an infant of a few months of age. Genetic linkage study of the families of the severely affected patients suggested linkage to the recently discovered SD locus on the long arm of chromosome 6. Locus heterogeneity therefore is an unlikely explanation of the phenotypic variation in SD. PMID- 7885533 TI - Audiologic manifestations in fetal alcohol syndrome assessed by brainstem auditory-evoked potentials. AB - In 29 of 36 children with fetal alcohol syndrome brainstem auditory-evoked potentials were performed and the auditory threshold was determined. The hearing of patients with a pathologic finding was then subject to a thorough ear-nose throat examination. Additionally the IQ was determined and an audiolinguistic examination was carried out. Seventy-five % of the children showed a peripheral hearing disorder on the basis of conductive hearing loss. In two children (7%) sensorineural hearing loss was located to the inner ear. A dysfunction of the auditory pathway was found in 6 patients (21%). The results of an isolated ear nose-throat examination in 7 further children supported these findings. The mean performances in the linguistic tests were far below average and displayed a strong relation to the IQ. This study shows that a peripheral hearing disorder, especially an obstruction of the auditory tube as well as dysfunctions of the inner ear and the central hearing pathway, are different manifestations of the fetal alcohol syndrome. An etiologic connection between craniofacial abnormalities in these children and an increased susceptibility to peripheral hearing disorders could not be demonstrated. To avoid a retardation of the linguistic development in addition to the intellectual deficits a strong emphasis must be put on an early and comprehensive auditory examination of children with FAS. PMID- 7885534 TI - Epilepsia partialis continua: follow-up with 99mTc-HMPAO-SPECT. AB - A three-year-old girl with epilepsia partialis continua involving the left side of the face and the left arm and leg was followed-up by 99mTc-HMPAO-SPECT in addition to EEG and CT. Increased regional cerebral blood flow was found in the right Rolandic area in the early stage of the disease, when the CT was normal and the EEG showed marked right hemispheric slowing. Seven months later severe hypoperfusion, extending to the right fronto-temporal region, and localised hyperperfusion in the right parietal area were observed by the 99mTc-HMPAO-SPECT when CT detected right hemispheric atrophy and EEG recorded severe epileptic activity, involving even the contralateral areas. The 99mTc-HMPAO-SPECT proved to be useful for the follow-up of the dynamics of the disease process. PMID- 7885535 TI - Hypometabolism and dipole localization in hemimegalencephaly: a case report. AB - A case of hemimegalencephaly was studied by means of neuroimaging (CT, MRI and PET) and magnetoencephalography (MEG). Hemimegalencephaly (HM) is a neuronal migration disorder. This is the first report of evaluation of HM with the use of PET and MEG from not only the morphological but also the functional point of view. PET with 11C-glucose showed a low radioactive concentration in the affected hemisphere, which suggested a metabolic deficit. MEG proved the epileptic foci existed mainly in the affected hemisphere, especially around a heterotopia and the pachygyric cortex, which was disclosed on MRI. PMID- 7885537 TI - Thalamic infarction in childhood due to extracranial vertebral artery abnormalities. AB - We report two children who developed thalamic infarctions which were demonstrated by CT. Both children had apparently normal angiograms although the extra cranial portions of the vertebral arteries were not demonstrated on the initial examination. Subsequent angiograms demonstrated abnormalities of the cervical portion of the vertebral arteries, dissection and pseudoaneurysm in one case and a large fusiform aneurysm in the other. Both children made full neurological recoveries. The thalamus is supplied by branches from the vertebro-basilar circulation and it is important to study the entire length of the extra cranial vertebral arteries as well as the intracranial vasculature. PMID- 7885536 TI - Pyridoxine-dependent seizures associated with white matter abnormalities. AB - Pyridoxine-dependent seizures are a disorder of GABA metabolism probably due to a defective binding of pyridoxal phosphate coenzyme (PALP) with glutamate decarboxylase (GAD), the rate-limiting enzyme in GABA synthesis. The resulting GABA deficiency causes severe epilepsy in infancy. We report on a boy with seizures starting soon after birth, and only controlled by pyridoxine at pharmacological dosages. After two months without seizures, a CT scan showed hypodense white matter in frontal and occipital lobes suggestive of a retarded or defective myelination. We are not aware of other descriptions of such morphological abnormalities in a patient with this disorder. PMID- 7885538 TI - Optic atrophy as the presenting sign in Hallervorden-Spatz syndrome. AB - A girl of eight years of age is described with the Hallervorden-Spatz syndrome. Optic atrophy with progressive visual loss was the only presenting symptom for three years. Behavioural and motor disturbances emerged after that time. Optic atrophy can be the first and for some time only symptom of the Hallervorden-Spatz syndrome. PMID- 7885539 TI - Spontaneous non-traumatic anterior compartment syndrome with peroneal neuropathy and favorable outcome. AB - We report a girl who spontaneously developed an anterior compartment syndrome with an associated deep peroneal neuropathy. Initial nerve conduction studies (NCS) recorded from the extensor digitorum brevis muscle demonstrated prolongation of the distal latency to 7.8 msec (normal contralateral side, 3.6 msec), and reduction in amplitude of the compound muscle action potential to 0.1 mV (normal contralateral side, 9.9 mV). Electromyography of the tibialis anterior muscle showed an absence of motor unit potentials. Serum creatine kinase was markedly elevated to 12,769 IU. Computed tomography (CT) showed evidence of necrotic muscle. One month later, the foot drop, repeat NCS, and CT demonstrated a significant improvement with conservative management. PMID- 7885540 TI - Epileptic EEG discharges during burst suppression. AB - Barbiturate anaesthesia is used in the treatment of status epilepticus and severe epilepsy of children. EEG is then used as a measure of the depth of anaesthesia, burst suppression being an easily identified EEG pattern. In this case report we describe epileptiform discharges during EEG suppression in two children undergoing barbiturate anaesthesia for treatment of intractable seizures. One of them had focal, rhythmic discharges of negative spikes on the positive suppression level. Bursts were readily produced by visual stimuli with flashes of red light but this did not increase the frequency of focal spike discharges after bursts. The other patient had generalised, high amplitude spike-wave complexes, which were easy to distinguish from the bursts. We emphasise that it is important to make a distinction between electrocerebral silence, or isoelectric EEG as it was previously called, from EEG suppression. It is also important to distinguish epileptiform discharges from bursts, if the intention is to keep the anaesthesia at EEG burst suppression level. PMID- 7885541 TI - Failure of early dextromethorphan and sodium benzoate therapy in an infant with nonketotic hyperglycinemia. AB - We report an infant with neonatal nonketotic hyperglycinemia (NKH), diagnosed early and treated with dextromethorphan (DM) and sodium benzoate therapy from the 65th hour of life. Initially the patient responded to treatment showing clinical and electroencephalographic improvement: myoclonic jerks disappeared, muscular tone, reactivity to stimuli and spontaneous movements increased, assisted ventilation was no longer necessary and bottle feeding was initiated successfully; on EEG the suppression-burst pattern disappeared and the background activity was well-organized. At three months of age he developed flexor spasms and hypsarrhythmia. In spite of increasing doses of DM as high as 40 mg/kg/day and persistent therapy with sodium benzoate the child progressively deteriorated and died at the age of 5 months and 7 days. We stress that the adverse clinical course occurred in our patient even though DM and sodium benzoate therapy was started much earlier than in other reported cases. It is possible that prenatal brain damage and probable genetic variants (i.e. absent or minimal residual enzymatic activity and interindividual variations in DM metabolism) affect the response to therapy. PMID- 7885542 TI - Familial vestibulocerebellar disorder. PMID- 7885543 TI - Cranial MRI in PKU: evaluation of a critical threshold for blood phenylalanine. AB - A group of 15 adolescent patients with PKU and good life time blood phenylalanine control was tested for white matter abnormalities on MRI. Five of the patients presented mild to moderate abnormalities in association with blood phenylalanine levels above 5.0 mg/dl. Patients with and without MRI changes could statistically not be discriminated by blood phenylalanine concentrations at the time of investigation as well as by phenylalanine levels of different time periods prior to MRI examination. PMID- 7885544 TI - Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome. AB - Pathological and clinical data from 56 patients operated on for craniopharyngioma since 1981 were analyzed to determine the utility of dividing patients with this tumor into distinct clinical groups based on recognized pathological type and to determine the prognostic import of brain invasion. Of the tumors in the 30 adult patients, 66% were adamantinomatous, 28% were squamous papillary, and the remainder were mixed. However, of the tumors in the 26 children, 96% were adamantinomatous and none were pure squamous papillary (P < 0.01). Forty-six percent of the children compared with 17% of the adults had brain invasion (P < 0.01). Brain invasion was present in 37% of the adamantinomatous but in only 13% of the squamous papillary tumors. Seventy-seven percent of the children underwent gross total resection (GTR) compared with 27% of the adults (P < 0.01). Sixty three percent of the squamous papillary tumors underwent GTR compared with 54% of the adamantinomatous and mixed tumors. Follow-up ranged from 7 to 187 months (mean, 49 mo). After subtotal resection, with or without radiation therapy, 58% of the tumors recurred compared with 17% recurrence after GTR (P < 0.01), with a mean time to recurrence of 34 months. In both tumor histological types, subtotal resection was associated with a higher rate of tumor recurrence compared with gross total resection. Among the subtotally resected craniopharyngiomas, 2 of the 3 (67%) squamous papillary and 11 of the 21 (52%) adamantinomatous and mixed tumors recurred. In contrast, among the totally resected tumors, none of the 5 squamous papillary and only 5 of the 25 (20%) adamantinomatous and mixed tumors recurred. There were no significant differences in Karnofsky performance status score, mortality rate, or visual and endocrine outcomes when comparing patients based on histological tumor type. When controlling for age and extent of resection, we found that brain invasion had no significant effect on recurrence rate in totally resected tumors. Based on the limited number of patients in this series, we conclude as follows. 1) Contrary to previous reports, squamous papillary craniopharyngiomas, like adamantinomatous tumors, may recur when subtotally resected. 2) For both tumor variants, the most significant factor associated with craniopharyngioma recurrence is the extent of surgical resection rather than histopathological subtype. 3) Contrary to prior hypotheses, brain invasion in totally resected tumors does not predict higher recurrence. 4) GTR is associated with a significantly lower recurrence rate and can be achieved without sacrificing functional outcome. PMID- 7885545 TI - Estrogen receptor gene expression in craniopharyngiomas: an in situ hybridization study. AB - Craniopharyngiomas are histologically benign epithelial neoplasms of the sellar region that frequently exhibit invasive and aggressive local growth. In this study, we have investigated the presence and cellular distribution of estrogen receptor messenger ribonucleic acid by in situ hybridization in 23 surgically removed craniopharyngiomas. All craniopharyngiomas studied, including 19 adamantinomatous and 4 papillary variants, uniformly expressed the estrogen receptor gene. In all cases, an intense estrogen receptor messenger ribonucleic acid hybridization signal was demonstrated; one localized exclusively to the epithelial cells of the tumor. Connective tissue and vascular elements were devoid of hybridization signal. Coexpression of the estrogen receptor protein was also studied by immunohistochemistry. Despite the relative abundance of estrogen receptor message in all cases studied, the estrogen receptor protein was focally but conclusively detected in only two tumors. The basis of this discrepancy is unclear. Progesterone receptor protein was also studied in all cases; however, its definitive presence was noted in only one instance and, in that case, in only occasional nuclei. The expression of the estrogen receptor gene by the proliferative epithelial elements of craniopharyngiomas raises the questions of a possible hormonal component to the genesis and/or progression of the craniopharyngiomas and a potential responsiveness to therapeutic hormonal manipulation. PMID- 7885546 TI - Cerebral oligodendroglioma: prognostic factors and life history. AB - The records of 137 patients with supratentorial oligodendroglioma treated surgically between 1953 and 1986 were reviewed. The tumors were rated histologically benign or malignant. In the 105 patients followed up with a minimum observation time of 5 years to December 1991, the mean postoperative survival was 90.2 months (standard error, 9), the median 64 months (standard error, 9.6), the 5-year survival rate 52.4%, and the 10-year survival rate 24%. Sixteen possible prognostic factors, broken down into two or more variables each, were considered in the survival study on univariate methods (5-year survival rate, survival curves, and Cox's hazard function) and on multivariate analysis according to Cox's stepwise proportional hazards model. The latter showed that variables correlated positively with survival were benign histological findings (P, 0.000), postoperative radiation therapy (P, 0.004), and time of operation from 1977 to 1986 (P, 0.044) in 105 patients of the whole series, and period of surgery from 1977 to 1986 (P, 0.000), subtotal or total surgical resection of the tumor (P, 0.001), and radiation therapy (P, 0.005) in the subgroup of 79 patients operated on for benign tumors. However, the most interesting point to emerge from the study was the relevance of admission clinical status to the survival of patients who did not receive radiation therapy and to the prognostic response of those who did. Of the 40 patients with seizures and negative neurological status- Clinical Syndrome A--the 10 who did not receive radiation therapy had survived as long as the 30 who did (5-year survival rate, 80 versus 67%; P, not significant; median survival, 122 versus 85 months; Breslow and Mantel-Cox P, not significant), whereas of the 65 patients with intracranial hypertension and/or neurological deficits--Clinical Syndrome non-A--the 18 who did not receive radiation therapy had short survival times, and the 47 who did fared significantly better (5-year survival rate, 11 versus 53%; P, 0.002; median survival, 32 versus 64 months; Breslow and Mantel-Cox P, 0.000). These findings were not significantly affected by the exclusion of malignant neoplasms and in the group of benign tumors, in which the histological characteristics have not been found to be significantly different between those with A and those with non A clinical syndrome, did not depend on different frequencies of subtotal or total tumor removal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7885547 TI - Changes in proliferating cell nuclear antigen expression in glioblastoma multiforme cells along a stereotactic biopsy trajectory. AB - Proliferating cell nuclear antigen, an auxiliary protein of deoxyribonucleic acid polymerase-delta, has been shown to be a reliable marker of nuclear deoxyribonucleic acid synthetic activity. We applied a monoclonal antibody to proliferating cell nuclear antigen to a series of serial stereotactic biopsies from patients with glioblastoma multiforme and found the proliferative activity to vary relative to biopsy location within or surrounding the solid tissue component of the tumor. Twenty-seven trajectories in 26 patients were analyzed, each consisting of two to five sequential 10 x 1.5 mm core biopsies (mean = 3). The proliferative index (PI) was greatest in those cells located at the solid tumor-infiltrated parenchyma interface. PI values were significantly lower in those biopsy cores located proximal (within infiltrated parenchyma) and distal (within solid tumor tissue) to the solid tumor-infiltrated parenchyma interface (median PI values, proximal to distal: 0.38, 0.66, 5.45 solid tumor-infiltrated parenchyma interface], 0.39, 0.09%). The mean PI values were significantly lower in neoplastic cells samples from regions of peripheral hypodensity on computed tomographic scans compared with those sampled from contrast-enhancing regions (0.9 and 3.91%, respectively). There was no significant difference in the mean PI values of neoplastic cells sampled from regions of contrast enhancement or central hypodensity (3.91 and 4.31%, respectively). PMID- 7885548 TI - Surgical management of arteriovenous malformations in the region of the ventricular trigone. AB - The results in the surgical management of 26 patients with arteriovenous malformations intimately related to the trigone of the lateral ventricle are presented. Three operative approaches were used in the series, including a transtemporal route through the inferior or middle temporal gyrus (15 patients), an interhemispheric approach (8 patients), and a transcortical parieto-occipital approach (3 patients). The surgical approach was chosen on the basis of the relationship of the arteriovenous malformation to the trigone, the presence and location of associated hematoma, and preoperative neurological deficits. This report emphasizes the use of surgical adjuncts that are instrumental in the management of these challenging lesions, including magnetic resonance imaging for precise localization and operative planning, preoperative embolization to obliterate deep arterial supply, and intraoperative ultrasound and angiography to aid in localization and to document complete excision of the arteriovenous malformation before closure. The results of the management of these 26 patients are as follows: 21 had no or minor neurological deficits and were able to resume premorbid activities; 2 had a fair result, being independent but unable to resume their premorbid occupation; 2 had a poor result and were dependent as the result of an incapacitating neurological deficit; and 1 died. PMID- 7885549 TI - Postoperative hematoma: a 5-year survey and identification of avoidable risk factors. AB - This study examines the surgical practice at the Wessex Neurological Centre over the 5-year period from 1989 to 1993 to determine the incidence of postoperative hematoma and to identify risk factors for a perioperative bleeding disorder. The study includes only those postoperative hematomas (at any site) that followed and were related to a neurosurgical operation and were surgically evacuated. The study is prospective for the year 1993 and retrospective for the preceding years. Over the 5 years, 6668 operations were performed and 71 postoperative hematomas were surgically evacuated, accounting for an overall rate of 1.1% of operations. The records were available for 69 cases. The most frequent diagnosis leading to postoperative hematoma was meningioma surgery with a rate of 6.2% of cases (13 of 211); followed by craniotomy for trauma, 3.7% (7 of 192); aneurysm surgery, 2.6% (11 of 428); and intrinsic supratentorial tumors, 2.2% (10 of 451). Postoperative hematomas were intraparenchymal in 43% of cases, subdural in 5%, extradural in 33%, mixed in 8%, and confined to the superficial wound in 11%. The overall mortality was 32% (37% for intraparenchymal and 12% for extradural). Risk factors for a perioperative bleeding disorder were present in two-thirds of the patients. Administration of antiplatelet agents (aspirin and nonsteroidal anti-inflammatory drugs) was the most commonly associated risk factor. At least 75% of these identified risk factors could potentially have been avoided or corrected. PMID- 7885550 TI - Effects of droperidol, pentobarbital, and ketamine on myogenic transcranial magnetic motor-evoked responses in humans. AB - Myogenic motor-evoked responses to transcranial magnetic stimulation of the motor cortex (tcmag-MERs) may become clinically useful for the noninvasive assessment of motor pathway conduction during surgery. However, application is hindered because most anesthetic regimens result in severe depression of tcmag-MER amplitudes. As part of our systematic attempts to identify anesthetic agents and supplements suitable for use during tcmag-MER recording, we studied the effect of bolus doses of pentobarbital (1.5 mg/kg), droperidol (0.07 mg/kg), or ketamine (1 mg/kg), administered intravenously, on compound muscle action potentials to transcranial magnetic stimulation in five healthy volunteers. The doses were chosen to be comparable with doses that might be suitable for supplementation of a nitrous oxide/opioid anesthetic technique. Droperidol administration resulted in sustained amplitude depression of both tibialis and adductor pollicis tc-MERs to 30 +/- 9% and 39 +/- 14% of baseline (P < 0.01). Tcmag-MER amplitude changes after pentobarbital were variable, ranging from no change to substantial amplitude depression (to 20% of baseline) in two subjects. In contrast, ketamine administration did not result in significant amplitude depression. In three subjects, tibialis anterior amplitude increased to 150 to 220% of control values in the first 10 minutes after ketamine. Onset latency was unchanged after any drug. These data indicate that tcmag-MERs are moderately depressed after droperidol and pentobarbital but well preserved after ketamine. Ketamine may be a more suitable supplement to opioid/nitrous oxide anesthesia than droperidol or pentobarbital. PMID- 7885551 TI - Reduction and stabilization without laminectomy for unstable degenerative spondylolisthesis: a preliminary report. AB - Fifty-two patients with unstable degenerative spondylolisthesis treated with the "AO internal fixator" and posterolateral fusion were reviewed. The major purpose of this study is to observe whether this pedicle fixation system could adequately decompress the nervous system tissue by the restoration of the spinal canal and, hence, replace the conventional decompressive laminectomy for the treatment of this disease entity. The results were satisfactory, showing that 92% of the patients with radicular pain, 89% of the patients with low back pain, and 86% of the patients with intermittent claudication improved postoperatively. Observing the results, only two groups of patients with unstable degenerative spondylolisthesis are not suitable for this treatment modality. The first group consists of those patients who have a spondylolisthesis with borderline instability. The second group consists of those patients who have a positive Laseque's sign. PMID- 7885552 TI - Magnetic resonance imaging signal changes in denervated muscles after peripheral nerve injury. AB - The evaluation of peripheral nerve disorders has traditionally relied on a clinical history, physical examination, and electrodiagnostic studies. Recent studies have used magnetic resonance imaging (MRI) to evaluate a variety of both nerve and muscle disorders. In this article, we describe the use of MRI, using short-tau inversion recovery (STIR) sequences, to evaluate muscle signal characteristics in a variety of peripheral nerve disorders. A total of 32 patients were studied, and 12 representative cases are discussed in detail. Increased STIR signal in muscle was seen in cases of severe axonotmetic injuries involving the transection of axons producing severe denervation changes on electromyography. The increased STIR signal in denervated muscles was seen as early as 4 days after the onset of clinical symptoms, which is significantly earlier than changes detected on electromyography. The MRI signal changes were reversible when the recovery of motor function occurred as a result of further muscle innervation. In cases of neurapraxic nerve injuries, characterized by conduction block without axonal loss, the STIR signal in muscle was normal. These findings show that MRI using STIR sequences provides a panoramic visual representation of denervated muscles useful in localizing and grading the severity of peripheral nerve injury secondary to either disease or trauma. MRI using STIR sequences may therefore play an important role in the prediction of clinical outcome and the formulation of appropriate therapy early after peripheral nerve injury. PMID- 7885553 TI - The superior orbital fissure: a microanatomical study. AB - The superior orbital fissure (SOF) is a small (3 x 22 mm), but functionally very important, region. The microsurgical anatomy of the SOF was studied on five adult, formalin-fixed cadavers. The vascular structures of three of them were injected with latex. The SOF contains the third, fourth, and sixth nerves, the ophthalmic branch of the fifth nerve, and the superior orbital vein. It is divided by the two tendons of the lateral rectus muscle: the superior part contains the fourth nerve, the frontal and the lacrimal branches of the ophthalmic division of the fifth nerve, and the superior orbital vein; the inferior part contains the superior and inferior branches of the third, the nasociliary, and the sixth nerves. In regard to surgical access to lesions involving the SOF, the question is often raised as to whether the dissection should be started from the cranial or the orbital side. The following procedure is recommended: 1) frontotemporo-orbital craniotomy; 2) resection of the lesser wing of the sphenoid bone, of the anterior clinoid, and of the superolateral part of the orbital roof and opening of the dura along the Sylvian fissure, with an extension to the frontal lobe and another extension to the temporal lobe; 3) incision of the periorbita in its superolateral part and identification of the frontal nerve; and 4) dissection of the frontal nerve in an anteroposterior direction. The fourth nerve will be found medially and inferiorly to the frontal nerve. The third nerve will be found inferomedially to the frontal nerve in the SOF, and the sixth nerve will be found inferiorly to the inferior branch of the third nerve. PMID- 7885554 TI - Bystander tumoricidal effect in the treatment of experimental brain tumors. AB - The retrovirus-mediated transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene into tumor cells renders them sensitive to the cytocidal effect of the antiviral drug ganciclovir. This method has shown promising results as a treatment for experimental brain tumors. These experiments indicate that a major mechanism for the effectiveness of HSV-tk retroviral gene therapy may be the bystander tumoricidal effect. The bystander effect was hypothesized to explain tumor eradication, given that the efficacy of in vivo gene transfer to tumor cells was less than 100%. We demonstrate, in this report, that the bystander tumoricidal effect is a major contributor to the tumoricidal effect of ganciclovir in cell culture experiments using the mouse K1735 C19 cerebral melanoma line, thereby expanding the observation of the bystander phenomenon to a broader range of tumor types. The bystander effect was studied in vitro by coculturing wild-type C19 melanoma cells with HSV-tk-expressing C19 (C19-STK) cells. A maximal tumoricidal effect was seen when only 1 in 10 tumor cells expressed the HSV-tk gene. This suggests that in effect, 1 tumor cell with the HSV-tk gene, when given ganciclovir, will destroy 10 neighboring or bystander cells. The destruction of bystander cells does not appear to be mediated by a soluble factor(s) released into the media but, rather, requires close cell proximity or cell contact. In addition, HSV-tk-expressing C19 cells can exert an antitumoral effect not only on wild-type C19 cells but also on cells from a variety of different tumor cell lines, including a human glioblastoma multiforme cell line, indicating that the bystander effect is not a cell line-specific phenomenon. Finally, we observed that the bystander tumoricidal effect could be harnessed directly without using retrovirus-producing cells to increase survival in the mouse C19 brain tumor model. The potential implications of our findings in treating human brain tumors are discussed. PMID- 7885555 TI - Postmortem magnetic resonance imaging of experimental spinal cord injury: magnetic resonance findings versus in vivo functional deficit. AB - The relationship between the severity of the posttraumatic functional deficit and findings on magnetic resonance imaging (MRI) was investigated in a rat model of experimental spinal cord trauma. Thirty Sprague-Dawley rats were subjected to an identical, moderate, contusion injury of the spinal cord. Control animals underwent laminectomy without cord injury. The severity of the functional deficit was assessed with the Combined Behavioral Score (CBS). Animals were killed at 3, 7, 14, 21, or 28 days after injury, and the fixed, excised spinal cords were studied with MRI at 1.9 T. The lesion length was measured on sagittal spin-echo MRI. The lesion length measured on MRI was highly correlated with the CBS functional score (r = 0.56, P = 0.002). There were significant correlations between lesion length as determined by MRI and by histological morphometry (r = 0.44, P = 0.02), between histological morphometric lesion length and CBS functional deficit (r = 0.76, P < 0.001), and between the area of residual white matter at the lesion epicenter, determined by histological techniques, and the severity of functional deficit (r = -0.59, P = 0.001). A qualitative estimate of the area of preserved white matter, derived from MRI, was significantly correlated with the severity of functional deficit (r = -0.56, P = 0.006). A multiple regression of MRI-determined lesion length and MRI estimate of residual white matter versus CBS explained more than 42% of the variability of the functional deficit among these animals subjected to the same weight drop injury. We conclude that MRI parameters are reliable predictors of the severity of neurological deficit in experimental spinal cord trauma. PMID- 7885556 TI - Experimental syringomyelia in the rabbit: an ultrastructural study of the spinal cord tissue. AB - Hydrosyringomyelia was produced experimentally by the injection of kaolin into the cisterna magna of the rabbit, and the ultrastructural changes of the spinal cord surrounding the syrinx were investigated 2, 4, and 6 weeks after injection by transmission electron microscopy. The ependyma at the ventral part of the central canal was flat and stretched, whereas, in the dorsal part, it was split, and the syrinx extended through the dorsal median plane in most animals. Extracellular edema was found in the subependymal white matter and in and around the posterior median septum. Many nerve fibers surrounding the syrinx were in varying stages of axonal degeneration. Myelin sheaths were split, thinned, and completely lost in many nerve fibers. In some fibers, the axons were totally lost, leaving the myelin sheaths as empty tubes. Astrocytic processes containing a large number of glial filaments covered the nerve fibers adjacent to the syrinx and partially replaced the edematous area. The perivascular spaces were enlarged, especially near the syrinx and in the dorsal white matter. Oligodendrocytes remained undamaged, and the remyelination by oligodendrocytic processes was seen on some denuded axons. Sometimes, this further remyelination was abortive, especially where the edema was severe. The ultrastructural changes of the neural tissue and their sequences were identical, in most respects, to those of hydrocephalus and noncommunicating syringomyelia. The oligodendrocytic remyelination with ongoing demyelination found in this model has many similarities to those in experimental hydrocephalus. PMID- 7885557 TI - Lateral exposure of the cervicothoracic spine for anterior decompression and osteosynthesis. AB - A lateral exposure of the cervicothoracic spine by an approach giving access to the anterolateral aspect of the vertebral bodies between C3-T10 is described. The approach of that region is obtained by the association of a cervicotomy and a standard thoracotomy with a costal flap situated at the place of the scapula. This approach was used for one patient with tumor invasion in the anterior part of the spinal canal on T1-T3; it allowed extensive resection of the three successive metastatic vertebral bodies and permitted stabilization of the spine. PMID- 7885558 TI - Bilateral chronic electrostimulation of ventroposterolateral pallidum: a new therapeutic approach for alleviating all parkinsonian symptoms. AB - The global improvement of all parkinsonian symptoms after stereotactic pallidotomy has been demonstrated by Leksell. Recently, Laitinen, re-evaluating this target in the neurosurgical treatment of Parkinson's disease, confirmed the real value of this approach, and emphasized the necessity of locating the lesion in the ventroposterolateral part of the pallidum internum. Because we know that high-frequency stimulation of the ventrolateral part of the thalamus has the same clinical effect on tremor as high-frequency coagulation, this technique has now been applied bilaterally in one session in three patients who have severe Parkinson's disease, with akinesia and levodopa-induced dyskinesias in the foreground. The very satisfactory clinical results, up to 12 months in the first case, confirm the observation of Laitinen, but with the difference that the approach discussed here is both nondestructive and reversible, and unwanted side effects are avoided. PMID- 7885559 TI - Primary intraosseous orbital hemangioma: a case report and review of the literature. AB - Primary intraosseous orbital hemangiomas are rare tumors. Only 25 cases have been reported in the literature. Very few of them have multiple orbital bone involvement. We report a case with extensive involvement of the orbital roof, the medial and lateral walls of the orbit, and the lesser and greater wings of the sphenoid, and describe a unilateral extradural frontotemporal approach to excise the tumor and decompress the right superior orbital fissure and both optic nerves. A brief clinical and radiological review of the literature is presented. PMID- 7885560 TI - Cerebellopontine angle osteoma causing trigeminal neuralgia: case report. AB - A case of cerebellopontine angle petrous bone osteoma manifesting as homolateral trigeminal neuralgia and causing a mild brain stem compression is presented. The literature concerning osteomas and particularly those affecting the temporal bone is reviewed. This is the second report of an osteoma located on the inner surface of the petrous bone and causing intracranial complications. Moreover, we discuss the intracranial tumors presenting with trigeminal neuralgia or atypical facial pain. PMID- 7885561 TI - Multifocal inflammatory leukoencephalopathy associated with levamisole and 5 fluorouracil: case report. AB - Levamisole and 5-fluorouracil have now become the standard chemotherapeutic regimen for patients with Stage III colon carcinoma. A case of multifocal inflammatory leukoencephalopathy secondary to levamisole alone or combination of levamisole and 5-fluorouracil is reported. Magnetic resonance imaging with gadolinium demonstrated multifocal contrast-enhancing frontal, parietal, occipital, and periventricular white matter lesions. A stereotactic biopsy revealed reactive gliosis and macrophage infiltration, without evidence of metastatic tumor. Despite continuation of 5-fluorouracil, resolution of contrast enhancing lesions on magnetic resonance imaging without further neurological sequelae occurred when levamisole was stopped. The patient died with evidence of systemic metastasis 6 months later. Autopsy examination of the brain revealed multifocal demyelinating lesions, with no evidence of metastatic tumor. Immunoperoxidase studies of demyelinated lesions demonstrated infiltrating macrophages strongly positive for Class II antigens, interleukin-6, and interleukin-1 alpha. Surrounding astrocytes were positive for granulocyte macrophage colony-stimulating factor. Small numbers of perivascular T cells were present. This patient represents the first autopsy documented case of levamisole associated multifocal inflammatory leukoencephalopathy. PMID- 7885562 TI - Idiopathic chronic hypertrophic craniocervical pachymeningitis: case report. AB - A 55-year-old woman with a unique form of chronic hypertrophic pachymeningitis involving the posterior fossa and upper cervical spine is reported. Unlike other cases previously described, the clinical picture was dominated by signs of increased intracranial pressure, lower cranial nerve disorders, and a progressive cervical radiculomyelopathy. The diagnosis was made by means of a contrast enhanced magnetic resonance imaging scan and confirmed by histological examination of the excised dura. Surgical treatment with removal of the hypertrophic dura provided temporary relief, although the natural history of the disease was not modified. Exhaustive bacteriological and histopathological studies failed to identify a specific cause for this diffuse hypertrophy of the cranial and cervical dura. The literature is reviewed, and other histologically documented cases are discussed. PMID- 7885563 TI - An anterior intradural neurenteric cyst of the cervical spine: complete excision through central corpectomy approach--case report. AB - The case of a cervical intraspinal neurenteric cyst in a 6-year-old boy is reported. The anterior intradural location of the cyst was confirmed by preoperative magnetic resonance imaging. Complete excision of the cyst was achieved through the anterior central corpectomy approach. The vertebral defect was reconstructed with autogenous fibular graft. The child made a complete neurological recovery without a mechanical problem either at the neck or at the graft donor site. PMID- 7885564 TI - Spinal tuberculosis with circumferential involvement of two noncontiguous isolated vertebral levels: case report. AB - We present a case of a 16-year-old boy with an atypical form of spinal tuberculosis, which circumferentially involved two noncontiguous vertebral levels without destruction of the adjacent vertebral bodies and intervertebral discs. The lesions caused paraplegia and loss of sphincter control, and they were confined to a single vertebra at each site; the findings more closely mimicked spinal malignancies. There was no evidence of pulmonary or other extrapulmonary tuberculous disease. The patient was successfully treated both surgically and medically using posterior decompression and a stabilizing procedure in combination with postoperative antituberculous therapy. Magnetic resonance imaging played a major role in determining the extent of the disease and the type of surgical procedure and in monitoring adequate medical treatment. PMID- 7885565 TI - Isolated lumbosacral neurenteric cyst with partial sacral agenesis: case report. AB - A case of an isolated intraspinal lumbosacral neurenteric cyst in a 5-year-old girl with partial sacral agenesis is reported. The cyst wall contained transitional epithelium and smooth muscle characteristic of the urinary bladder, suggesting a possible cloacal origin of the cyst. No prior cases of concomitant neurenteric cysts with partial or complete sacral agenesis have been reported, and the occurrence of an isolated intradural extramedullary sacral neurenteric cyst is rare. The possible pathogenesis of this lesion is described. PMID- 7885566 TI - Carcinoid tumor of the sacrum: case report. AB - We present a case of isolated carcinoid tumor of the sacrum and highlight the unusual nature of this lesion. The histopathology suggests hindgut cause, and we discuss the possibility of an underlying congenital tailgut cyst. We review the pathology of these rare anomalies with reference to embryological development and known instances of carcinoid focus. We also present previous reports of sacral carcinoid. PMID- 7885568 TI - The United States Neurological Surgery Residency Matching Program. AB - After 3 years of deliberations, The Society of Neurological Surgeons approved a national Neurological Surgery Matching Program in 1983 for residency positions beginning July 1, 1985. All directors of United States neurological surgery residency training programs agreed to participate and abide by the rules of the match. A review of 10 years' experience with 11 matches from 1983 to 1994 indicates full acceptance by both applicants and program directors and a highly successful process and outcome, satisfactory for everyone except for qualified applicants who failed to obtain a residency position. Since 1985, 1455 neurosurgical (Postgraduate Year 2) residency positions have been offered for match, and 2708 applicants have submitted a ranking list, filling 1434 positions with the initial computer run each year and leaving 1274 unmatched applicants. Thus, the ratio of applicants to available positions is almost 2:1. Various interesting details about multiple-year applications, International Medical Graduates, and nonstart, transfer, and dropout rates are presented, including the eventual practice activities of residents not completing neurosurgical training. A comparison of all United States medical schools, considering data on applications and matches for neurosurgical residency versus number of senior medical students, reveals wide differences. These differences are probably related to the availability of neurosurgical clerkships, faculty participation in the undergraduate curriculum, and the presence of a neurosurgical residency program. PMID- 7885567 TI - Reconstruction of the hypoplastic posterior arch of the atlas with calvarial bone grafts for posterior atlantoaxial fusion: technical report. AB - Posterior atlantoaxial fusion is a common procedure performed for instability at C1-C2. This operation requires intact posterior elements of both the atlas and the axis. When this is not the case, the incorporation of the occiput and the lower spinal segments is usually required for adequate posterior fusion, but such a procedure limits the mobility of the upper cervical spine. A technique for the reconstruction of the posterior arch of the atlas with calvarial bone is described in this report. This technique allowed the successful fusion of the C1 and C2 vertebrae in a patient with traumatic atlantoaxial subluxation who also had a congenital absence of the posterior arch of the atlas. PMID- 7885569 TI - Protein kinase C and growth regulation in malignant gliomas. PMID- 7885570 TI - Neurosurgery online. PMID- 7885571 TI - Magnetic stimulation of the facial nerve: strong clinical and experimental evidence places the excitation site to the labyrinthine segment of the nerve. PMID- 7885572 TI - Re: "Motor and sensory cortex in humans: topographic study with chronic subdural stimulation". PMID- 7885573 TI - Closure of cerebrospinal fluid leakage after transsphenoidal surgery: technical note. PMID- 7885574 TI - Transcranial Doppler ultrasonic assessment of middle cerebral artery blood flow velocity changes during verbal and visuospatial cognitive tasks. AB - Hemisphere specific changes of blood flow velocity in the right and left middle cerebral artery (MCA) induced by cognitive demands of verbal and nonverbal tasks were examined by means of a newly developed technique of simultaneous bilateral transcranial ultrasonic Doppler sonography (TCD). Thirty-one right-handed healthy volunteers served as subjects. Identical stimulus and response procedures were used with all tasks to avoid possible differential effects of these conditions on blood flow velocity. Compared to the preceding resting phase, the increase in flow velocity induced by each of the verbal tasks (sentence completion, similar or contrasting word meaning, similarities) proved to be significantly higher in the left than in the right MCA. Among the non-verbal visuospatial tasks only the "identical pictures" (perceptual speed) task led to a complementary higher increase in right MCA blood flow velocity. No such asymmetry in blood flow acceleration was observed, however, with the tasks "figure assembly" and "cube comparison" which require visualization and mental rotation of figures. The findings underline the recently emerging uncertainty in neuropsychological research with regard to the functional specialization of the right hemisphere. PMID- 7885575 TI - Living and non-living categories. Is there a "normal" asymmetry? AB - A picture naming task and a semantic memory verbal questionnaire were given to normal subjects to assess the possible asymmetry between knowledge for non-living and living things. We first examined 60 elderly subjects with low education. Asymmetry between non-living and living things was found in the semantic knowledge questionnaire and living things fared worse. This difference was not explained by discrepancy in item frequency, familiarity or prototypicality. Using the same questionnaire, we analysed difficulty judgements given by younger, better-educated subjects: questions about living things were slightly, but significantly more difficult than questions regarding non-living things. In order to check for a possible sample bias, we submitted another verbal questionnaire with an analogous structure to different judges and replicated the previous results. These findings are discussed with regard to the selective semantic memory deficit for living things observed in patients. We suggest that the cognitive pattern presented by these cases may be linked to, but not fully explained by the greater difficulty living things present for normal subjects. PMID- 7885576 TI - Multiple meaning systems in the brain: a case for visual semantics. AB - In this study we report our investigations of a category specific visual associative agnosia. The patient D.R.S.'s spoken language skills were excellent. Although he could name objects from their description, he was unable to name them by sight nor was he able to mime their use. On visual-visual matching tasks his performance was impaired and affected by semantic proximity. In two tasks his knowledge of visual objects was demonstrated to be significantly more impaired than his knowledge of visual living things. It is argued that these findings support a multiple knowledge base hypothesis. PMID- 7885577 TI - Can commissurotomized subjects compare digits between the visual fields? AB - Sergent (Brain 113, 537-568, 1990) flashed pairs of digits to the opposite visual fields of three commissurotomized subjects (L.B., N.G. and A.A.), and found that they were highly accurate in deciding which digit was the larger, but at little or no better than chance in deciding whether the digits were the same or different. Experiment 1 confirmed that these subjects were better at relative than at same-different judgements. However their performance on relative judgements was considerably lower than in Sergent's study and could be explained largely in terms of the subjects' use of information available to a single hemisphere. A fourth subject, D.K., with section of the posterior corpus callosum only, had little difficulty with either task despite previous evidence of visual disconnection, and appeared able to transfer the information verbally. In Experiment 2, L.B. was better able to make both relative and same-different judgements when the digits were presented within either the left or right visual fields than when they were presented in opposite fields. These results suggest little, if any, interhemispheric transfer of either shape or numerical information following complete forebrain commissurotomy. PMID- 7885578 TI - Word retrieval to letter and semantic cues: a double dissociation in normal subjects using interference tasks. AB - Recent evidence suggests that letter and semantic category verbal fluency tasks may use different component processes of a distributed word retrieval system. We hypothesized that the retrieval of words that begin with the same letter places greater demands on frontal lobe mediated strategic search processes than on temporal lobe mediated semantic knowledge. Conversely, generation of words from the same semantic category places greater demands on semantic knowledge than on strategic search. This hypothesis was tested by requiring subjects to generate lists of words to letter and semantic cues alone and while performing an interference task. A motor sequencing task (developed by Moscovitch, Neuropsychology of Memory, pp. 5-22, 1992) was used to activate frontal regions and an object decision task was used to activate posterior temporal cortex. In support of the hypothesis, letter fluency was reduced to a greater extent by concurrent performance of the motor sequencing task than by the object decision task. The opposite interference pattern was found for semantic category fluency. PMID- 7885579 TI - Walking trajectory and hand movements in unilateral left neglect: a vestibular hypothesis. AB - This is the first systematic study of walking trajectories in unilateral neglect. Six patients with unilateral left neglect approached and walked through a doorway, and all six deviated to the right of centre when doing so. Four out of six significantly centred their walking trajectories by making left hand movements while approaching the doorway. The group effect of walking with no hand movements vs walking with hand movements was statistically significant. Age matched control patients showed a similar but significant smaller rightward deviation. The results are interpreted in terms of recent research in limb activation effects on neglect (Robertson and North, Neuropsychologia 30, 553-563, 1992), and also in the light of research showing close anatomical correspondence between the cortical projections of the vestibular nerve on the one hand, and the hand/arm representational fields of the central sulcus on the other. PMID- 7885580 TI - How reliable are occipital asymmetry measurements? AB - In vivo occipital asymmetry (OA) measurements have been used to infer functional asymmetries such as language dominance. We investigated the degree of correlation between OA measurements derived by the same rater from different scans of the same subject. We used magnetic resonance (MR) and computerized axial tomography (CT) to study correlations between MR:MR, CT:CT and CT:MR. The highest intrasubject correlation was for MR:MR (r = 0.79). The CT:CT value was similar (r = 0.78) and the CT:MR correlation was slightly lower (r = 0.72). The findings indicate that the reliability of occipital asymmetry measurements is modest at best, setting a low ceiling on the valid use of this variable to infer other indexes. PMID- 7885581 TI - Prevalent direction of reflective lateral eye movements and ear asymmetries in a dichotic test of musical chords. AB - Subjects who consistently move their gaze either to the right or to the left while reflecting on visuo-spatial or verbal questions are usually called "lateral eye movers". This study evaluated auditory asymmetries to a dichotic test of musical chords in 23 right-handed females, selected through test-retest as reliable lateral eye movers; 12 were "left movers" (LMs) and 11 were "right movers" (RMs). During the assessment of the prevalent direction of gaze as well as during the dichotic test, the oculomotor activity was controlled through a video camera. The hypothesis was that the left ear advantage usually found with dichotic chords is enhanced in LMs and reduced in RMs, and that this effect is not due to the facilitating influence of lateral eye movements occurring during the task. Results show that: (a) left movers exhibit a marked advantage of the left ear while right movers do not exhibit any significant ear advantage; (b) despite the instruction to fix a central point, lateral movers tend to show unwarranted eye movements in their usual direction; (c) the effect of the prevalent direction of gaze on the dichotic advantage is not due to eye movements made during the dichotic test. These findings give further support to the hypothesis that the tendency to consistently shift the gaze to one side is related to hemispheric asymmetries as measured by lateralized tests. PMID- 7885583 TI - Management of the patient with stroke. PMID- 7885582 TI - A dissociation in the relation between memory tasks and frontal lobe tests in the normal elderly. AB - In this study a group of elderly subjects were examined on three tests of frontal lobe function. Two of these tests, FAS word fluency and the Alternate Uses Test, were considered tests of spontaneous flexibility, as defined by Eslinger and Grattan [Neuropsychologia 31, 17-28, 1993]. The third, the modified Wisconsin Card Sorting Test (WCST), is considered a test of reactive flexibility. Performance on two tests of memory, release from proactive interference (PI) and a matched recall and recognition test was also measured. The elderly were shown to be impaired on all tests when compared with young controls. Analysis revealed that release from proactive interference was significantly correlated with performance on alternative uses but not WCST while the size of subjects' discrepancy between recall and recognition correlated strongly with WCST but not with Alternate Uses. In addition there was a strong correlation between the two measures of spontaneous flexibility but these measures did not correlate with WCST. Performance on the two measures of memory was also uncorrelated. The data indicate that the pattern of frontal deterioration in the elderly does not comprise a single deficit and, furthermore, that the relationship between frontal dysfunction and normal age-related memory loss is not unidimensional. PMID- 7885584 TI - Risk factors and outcomes for ischemic stroke. AB - Stroke continues to have a great impact on public health in the United States. Stroke is frequent, recurring, and is more often disabling than fatal. The annual incidence of new strokes in the United States is nearly one half million, with over 3 million stroke survivors alive today. Identifying risk factors for initial ischemic stroke, as well as characterizing the determinants of outcome (stroke recurrence and mortality) after ischemic stroke, is the basis for stroke prevention strategies. Modifiable and nonmodifiable risk factors for ischemic stroke have been identified and include age; gender; race/ethnicity; heredity; hypertension; cardiac disease, particularly atrial fibrillation; diabetes mellitus; hypercholesterolemia; cigarette smoking; and alcohol abuse. New risk factors, such as hypercoagulable states and patient foramen ovale, are currently being investigated. Follow-up studies have quantified case-fatality rates, early recurrence risk, and long-term mortality and recurrence risks. Despite advances in stroke prevention strategies and treatments, stroke recurrence is still the major threat to any stroke survivor. A major goal set by the Public Health Service in its National Health Promotion and Disease Prevention Objectives for the year 2000 is "to reduce stroke deaths to no more than 20 per 100,000." Part of this can be achieved if the risk of stroke recurrence is reduced. However, the frequency and determinants of stroke recurrence are poorly understood. Data from epidemiologic studies can help identify risk factors and outcomes after ischemic stroke, as well as the selection of high-risk individuals for focused risk-factor modification. Current information on these topics is discussed. PMID- 7885585 TI - Management issues for patients with ischemic stroke. AB - This review briefly summarizes the acute management of cerebral infarction and cardiac comorbidity in patients with stroke, with a focus on more general aspects of care. Important aspects of the acute management of cerebral infarction are its prompt recognition, use of appropriate emergency medical services, including 911, initial treatment, and prevention of complications. Secondary prevention begins with the diagnostic workup for the cause of the initial stroke. Although the optimal workup depends on the patient, a minimal workup consists of a history and physical examination sufficient to establish vascular risk factors and the neurologic and medical status of the patient, basic laboratory tests, ECG, chest x-ray, cranial CT, evaluation of carotid arteries, and a search for cardiac sources and the presence of atrial fibrillation. Further workup may include a search for coagulopathies, less common sources of embolism, and intracranial intravascular disease. Better education of patients at risk of vital importance. Patients with cerebral infarction share vascular risk factors with those who have coronary disease, and the presence of both coronary and cerebrovascular disease is highly likely. The likelihood of finding coronary artery disease in patients with transient ischemic attack and ischemic stroke with noninvasive testing, as well as management recommendations for these patients are reviewed. PMID- 7885586 TI - Stroke prevention therapies and management of patient subgroups. AB - Stroke is the third leading cause of death in the United States. Efforts directed at reversing acute cerebral ischemia are promising but are hampered by multiple logistic and physiologic barriers. Prevention of stroke, therefore, remains of critical importance. Primary prevention is accomplished through reduction of risk factors and the appropriate use of warfarin or aspirin in patients with cardiac sources of emboli such as atrial fibrillation. Secondary prevention is designed to reduce the risk of stroke in patients with known stroke precursors, including transient ischemia, reversible ischemic deficits, and completed stroke. Aspirin and ticlopidine are two antiplatelet agents with an established role in secondary stroke prevention. In a major North American clinical trial, ticlopidine demonstrated superior efficacy to aspirin for the prevention of recurrent stroke, particularly in the first year following a stroke. Dipyridamole has not been shown to be useful for stroke prevention. The role of warfarin in the prevention of recurrent noncardiogenic stroke remains controversial and is currently under investigation. Stroke prevention remains an important challenge, and therapy should be individualized to achieve optimal results. PMID- 7885587 TI - Optimizing long-term patient compliance. AB - The key elements for enhancing patient compliance when prescribing are selecting the fewest number of daily doses (taking patient's other medications into consideration), scheduling when doses are to be taken, and helping the patient select an appropriate reminder or "cue." Developing reminder cues, such as clock time, meal time, or bathroom ritual, requires only a few minutes of careful planning to mesh with the patient's lifestyle. If one type of cue is not successful, another or combinations of cues are tried over time. Asking patients about their cues at each visit not only helps patients develop personalized cuing systems, but also reminds them that their physician has a consistent interest in the way they take their medication. Unfortunately, no single specific strategy will enhance compliance in all patients. Physicians have the greatest influence on medication compliance when they provide specific suggestions that fit into the patient's lifestyle. PMID- 7885588 TI - Assessment and psychologic factors in stroke rehabilitation. AB - With improved survival after stroke, it is important to identify those patients whose quality of life can be enhanced through rehabilitation. The decision for rehabilitation is based on several factors: type and severity of neurologic deficits, cognitive status, physical endurance, and preferences of patient and family. Implementation requires identification of learning patterns, sensitivity to the patient's responses, and establishment of realistic goals. Systematic assessment of impairments and disability is valuable for describing the impact of the stroke, monitoring recovery, evaluating response to specific interventions, and determining their long-term benefits. Because of the range of potential impairments, it is important to use a battery of assessment measures and to incorporate specific measures during each stage of recovery. In addition to assessments for neurologic disabilities, assessments for psychosocial conditions are necessary, as depression and dysphoria occur commonly and affect the rehabilitation and recovery of stroke patients. Their influence on physical function is currently being debated in the medical literature. The social context in which a stroke patient recovers also has profound effects on the success of the recovery process. Such factors as the amount of social support, income level, race, and life satisfaction affect the patient's rehabilitation process and adjustment. Standardization of assessment measures and a better understanding of the psychosocial factors that influence rehabilitation are necessary for helping stroke patients achieve an optimum functional quality of life. PMID- 7885589 TI - The economic impact of stroke. AB - Estimates of the total cost of stroke in the United States vary widely, ranging from annual health care expenses of $15 billion to $30 billion when the patients' lost wages are included. As a result of increasingly shorter acute hospitalizations under the DRG-based Prospective Payment System, medical costs paid by Medicare have stabilized. Data from Medicare show that people over age 64 years account for 87% of all deaths and 74% of all hospitalizations for cerebrovascular disease. Data through 1986 indicate that cost-containment measures did not appear to affect outcomes negatively or lead to more complications that would likely add to the cost of hospital care. Shorter inpatient rehabilitation stays are also a product of Medicare reimbursements and of capitated care. The mean cost across regions of the United States for inpatient rehabilitation is three to four times that of an acute hospital stay; however, only a minority of stroke survivors receive this level of care. The greater availability of nursing homes and a decline in age-adjusted death rates that might leave more patients disabled could raise some costs, whereas more widespread management of risk factors might decrease stroke rates and the severity of disability. PMID- 7885590 TI - American Academy of Neurology 47th annual meeting. 1995 Abstract listing and general meeting information. Seattle, Washington, May 6-13, 1995. PMID- 7885591 TI - Billig's innocence. PMID- 7885592 TI - Improving military trauma care. PMID- 7885593 TI - U.S. military working dogs with Vietnam service: definition and characteristics of the cohort. AB - We verified and corrected inaccuracies in descriptive profile information on military working dogs (MWDs) that died from 1965 to 1980 and were reported in the Armed Forces Institute of Pathology Registry of Veterinary Pathology. Using other available military records, we determined which dogs served in Vietnam. Identified were 3,895 MWDs with a unique identity tattoo that served in Vietnam, of which 2,389 served exclusively with U.S. military forces and died in Vietnam. Another 479 Vietnam veteran MWDs completed their service elsewhere. This overall effort resulted in signalment corrections, generally age at death, in 21% of the Registry MWD accessions during the study period. The improved definition and characterization of the Vietnam cohort will lead to greater precision in epidemiologic investigations of the health effects from the Vietnam experience in U.S. military working dogs. PMID- 7885594 TI - Effect of impulse noise on the auditory brainstem response of the fetal sheep and the adult ewe: case study. AB - Auditory brainstem responses (ABR) were obtained from a sheep fetus in utero and from a nonpregnant ewe before and after a noise exposure generated by 10 105-mm howitzer impulses (160-166 dB peak pressure). Fetal ABR thresholds shifted by less than 15 dB, whereas the adult thresholds shifted more than 50 dB. Comparison of exposed and nonexposed fetal cytocochleograms revealed minimal sensory cell loss in two age-matched animals. Although fetal ABR threshold shifts were noted in this study, the magnitude of shift was modest when compared to the significant elevation of the adult ABR thresholds. PMID- 7885595 TI - The evolution of nursing research in the Army Nurse Corps. AB - The growth of nursing research has been richly nurtured in the military nursing community. Army nurses have been at the forefront of the growth of the discipline both within the military community and at civilian institutions after their departure from active duty. This paper describes the development of the nursing research program by the Army Nurse Corps (ANC) within the Army Medical Department (AMEDD) from its earliest stages through the present. It discusses the organizational structure of nursing research within the ANC and the leadership innovations being implemented to make nursing research responsive to the needs of the AMEDD into the next century. PMID- 7885596 TI - Mass casualties on the modern battlefield: a view from the 1st Armored Division (US). AB - Operations Desert Shield/Desert Storm will go down in history as a resounding success. However, future successes will depend on how much we take away from this experience in the form of lessons learned. This article is a warning message on the need for medical preparedness. The medical personnel shortage remains a problem for both commanders of field units and medical staff. The Professional Filler System, which provides clinicians to deploying combat medical and line units, is not aggressively administered and maintained. Medical Tactical Standard Operating Procedures are not fully integrated, nor are they used in Mission Essential Task List training. LOGOVERWATCH has potential but needs refinement. Finally, important medical and communication equipment needs upgrading to current state-of-the-art standards. On the plus side, the Combat LifeSaver program works well for intensive training on chemical casualties care. Combined with the high state of training and motivation of soldiers and medical professionals, many of the current shortcomings have been masked. This situation cannot go on indefinitely without a degradation of mission capability. PMID- 7885597 TI - Patient attitudes and utilization patterns in Army medical treatment facilities. AB - In Section 733 of the National Defense Authorization Act for Fiscal Years 1992 and 1993, Congress directed the Department of Defense to study the military medical care system. When the Congressionally directed study findings become available, baseline data will be needed for comparison. From 1989 to 1992, patient satisfaction surveys were conducted of eligible beneficiaries who might seek health care in Army military medical treatment facilities (MMTFs). Regression models were developed to predict overall quality of care. Most of the beneficiaries are generally satisfied with the Army health care system. However, care provided by CHAMPUS, private, or other sources is rated more satisfying than that in MMTFs. Retired personnel were most satisfied, whereas active duty dependents were the least satisfied group. PMID- 7885598 TI - Sharing the tools of primary care. AB - Emphasizing community-based primary care as the dominant mode of clinical practice presents an opportunity for greater self determination among retirees, dependents, and active duty personnel. Physician certification of patients' knowledge of personal profiles, problem lists, medication lists, and plans- described as the tools of primary care--permits patient and doctor agreement on mutual agendas of prevention as well as treatment. This opening for primary care involves interaction among all three of the variables in classic medicine- doctors, illnesses, and patients. PMID- 7885599 TI - Professional and organizational values of male and female U.S. Public Health Service commissioned officers. AB - A study was conducted to determine the organizational and professional values held by male and female physicians, nurses, and pharmacists serving in the U.S. Public Health Service. An existing instrument was modified to measure health professionals' organizational values and professional values. These values were analyzed by multivariate and multiple regression techniques to ascertain the relationship the independent variables sex, age, marital status, race, and practice type of the health professionals had with the levels of each measurement. Sex, age, marital status, race, and practice type appeared to affect the values held in varying degrees. Differences between organizational and professional values held by the health professionals will have an effect on future roles for officers in the U.S. Public Health Service. There will also be an impact on society as the nation decides the future direction for health care. PMID- 7885600 TI - Research for graduate medical education. AB - Several important questions are addressed herein. What is graduate medical education (GME), and what is research? What is the history of the association between GME and research? Why is research required for GME? What research is required for GME? How will health care reform affect GME and biomedical research? How much research is done in the United States? How can the value of research be assessed? What can we expect for the future with respect to GME and research? PMID- 7885601 TI - Hospital integrated lanes training: brigade-directed implementation of a medical lanes training program during annual training. AB - The "lanes" concept of training was integrated into a medical site support mission of the 804th Medical Brigade, U.S. Army Reserve, during Annual Training, 1993 at Fort Drum, New York. This training, termed Hospital Integrated Lanes Training (HILT), included STX, FTX, patient play, and full use of Deployable Medical Systems equipment. The medical care of over 33,000 personnel participating in tactical annual training exercises was not interrupted during any concurrent phase of lanes training. Brigade operations planners developed an array of medical exercises that involved both moulaged and paper patient play. These exercises began prior to hospital set-up and continued for 24 hours a day throughout the tactical exercise. Injuries likely to be encountered during combat operations were inserted into the play singly and under a mass-casualty scenario. The standard of care for all injuries was determined with the Army Medical Department Center and School guidance. Prior coordination of brigade medical assets with external air and ground ambulance organizations broadened the scope of the training and facilitated effective use of command and control, communications, and equipment over a wide geographic area. Medical records were collected and evaluated at the conclusion of all exercises. After-action reviews were conducted by all medical units to assist in the planning of future HILT exercises. The HILT concept is a valuable tool for the complex training requirements of field medical units organized under medical Force 2000. The concept of integrated lanes training allows for the development and continuous improvement of individual and sectional skills for medical personnel and should be applied within all echelons of care. PMID- 7885602 TI - The role of intramedullary nailing in modern treatment of open fractures of the tibia and femur. AB - The increasing incidence of open tibial and femoral fractures causes great suffering by patients and is an enormous economic burden, necessitating improved treatment. The current treatment of these fractures is reviewed, as well as the evolving role of intramedullary nailing in this treatment. Intramedullary nailing seems to give better results than external fixation in Gustilo type I and II fractures, and is at least as good in type III. The introduction of the non reamed interlocking intramedullary nail may bring about even better outcomes. Any improvements in treatment should be based on thorough understanding of the biology and biomechanics of the injury. PMID- 7885603 TI - The transverse-vertical frenuloplasty for ankyloglossia. AB - Ankyloglossia is a congenital anomaly in which the frenulum is attached to the tip of the tongue to varying degrees. Children affected by this condition may be unhindered or they may have a variety of problems to include dysfunctional breast feeding and speech mechanics. This article describes the indications for and surgical technique of the transverse-vertical frenuloplasty for the treatment of ankyloglossia. PMID- 7885604 TI - Tuberculous peritonitis in a young female diagnosed using mini-laparotomy: a case report. AB - An 18-year-old female Pacific Islander with abdominal pain, ascites, and fever was transferred to our hospital with suspected ovarian malignancy. These nonspecific clinical features of tuberculous peritonitis in a female frequently contribute to misdiagnosis. Preoperative findings included negative sputums, negative purified protein derivative, and no acid-fast bacilli (AFB) found in peritoneal fluid or fine needle biopsy of the omentum. Tuberculous peritonitis was diagnosed after omental biopsy obtained at mini-laparotomy showed granulomatous inflammation and positive isolation of AFB. PMID- 7885605 TI - Therapeutic lithium-related cardiac conduction disturbance in a previously healthy patient: a case report. PMID- 7885606 TI - Lower extremity amputation in a Marine veteran 22 years following vascular injury in Vietnam. AB - Injuries of the extremities are common in combat. This patient sustained a vascular injury to his left leg, but he did not experience any medical problems for 18 years after initial injury. In 1988, he began to experience repeated problems with graft occlusion. After 4 years of repeated surgical intervention and medical treatment, the patient had surgical amputation of his left leg. PMID- 7885607 TI - Complications of suicidal hanging: a case report and brief review. AB - Suicide remains a significant societal dilemma commonly presenting as an acute medical emergency. Presented is a report of a near-hanging suicidal attempt by a 30-year-old, active duty Navy man. This case documents local injuries and neurologic and cardiopulmonary complications of near-fatal suicidal hanging, which is a common method of suicide in the United States. PMID- 7885608 TI - [Combined use of goserelin acetate and human menopausal gonadotropin in the induction of follicular growth in a program of fertilization in vitro and embryo transfer]. AB - OBJECTIVE: to investigate the efficacy of a gonadotropin-releasing hormone analogue (GN-RH-a) in combination with human menopausal menotropin (hMG) for in vitro fertilization. METHODS: 30 infertile women aged 32 to 37 years received a combined treatment with a long-acting slow-releasing Gn-RH-a and hMG to perform ovarian stimulation in a program of in-vitro fertilization. Serum levels of Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), 17-beta-estradiol (E2), Progesterone (P), were evaluated and transvaginal ultrasonographic examinations were performed during the treatment to assess the ovarian volume, the mean number and diameter of growing follicles and the endometrial morphology and thickness. Oocyte retrieval was performed by transvaginal-ultrasound-guided approach, 24-36 hours after the administration of human chorionic gonadotropin (hCG). RESULTS: our data suggest that the combined use of Gn-RH-a and exogenous gonadotropins is associated with a more uniform ovarian response and with the absence of premature LH discharge. Moreover, the Gn-RH-a as polymer implant provides a controlled delivery per day over a one-month period and avoids the inconvenience of a daily administration. CONCLUSIONS: this kind of Gn-RH-a formulation, in in-vitro fertilization programs, appears very effective in inducing a reversible hypogonadic state, easy to manage and well tolerated by the patient. Its association with exogenous gonadotropins appears to be effective in increasing the success rate of good quality oocyte retrieval. PMID- 7885609 TI - [Chlamydia trachomatis infection and its correlation with cervical preoncogenesis]. AB - Among 612 patients included in this open study, serologic detection of Chlamydia infection was compared with cervical cytologic, histologic and colposcopic abnormalities. Serologic and cytologic evidence of elevated exposure to Chlamydia among patients with squamous intraepithelial lesions was found. Nevertheless, whether the Chlamydia infection represents a non casual association resulting from the correlation with sexual activity or it plays independent or supporting etiologic roles is an issue that warrants further investigations. PMID- 7885610 TI - [Bacterial vaginosis. Prevention of recurrence]. AB - Bacterial vaginosis (BV) is the main cause of vaginitis. The condition is characterised by an abundant and odorous vaginal loss, but more than half the patients with demonstrable signs of BV do not report symptoms at all. Gardnerella vaginalis (Gv) is often associated with BV, but it is not the sole factor responsible, as is shown by the fact that it can be isolated in the vagina of women withBV. In 1992 and 1993, 2630 patients, 1460 of them gynaecological and 1170 obstetric, were admitted to the Obstetrics and Gynaecology Clinic of Parma University. Amsel criteria were adopted for diagnosing BV. Cases of BV were treated with 5 mg/die 2% clindamycin vaginal cream for 7 days. In the event of recurrences, 250 mg tablets of metronidazol were added: 8 tablets in 4 administrations in a single day, treatment also being extended to the partner. Patients admitted in 1993 received a protocol of hygienic and behavioural standards, stress being laid on prophylaxisa measures even after the end of therapy. BV proved to be present in 12.3% of cases, of whom only half were symptomatic. The situation was practically stationary if the 2 years are considered separately. Recurrences of symptomatic bacterial vaginosis were 15% in the absence of protocol application and 8.3% after the protocol. Recurrences were less frequent in the asymptomatic forms. Compared to the total number od cases of BV, recurrences were significantly low (12.1% p < 0.001). PMID- 7885611 TI - [Needle aspiration of ovarian cysts. Our experience]. AB - 80 patients underwent ultrasound guided cyst puncture of ovarian cysts. Six patients were pregnant and in four of them needle aspiration was executed through the transvaginal tract. The sediment aspirated was examined by a cytologic method and when possible it was also correlated to a histological test. Technique and results have been dealt with. No relevant complication was found. Finally, the echoguided (induced) needle aspiration is a simple and safe method to treat benign ovarian cysts in fertile women. It is particularly advisable in pregnancy and in patients for whom both laparascopy and traditional surgery are not practicable. PMID- 7885612 TI - [Ultrasonographic monitoring of the endometrium in post-menopausal women asymptomatic or undergoing hormone replacement therapy]. AB - This study evaluated the reliability of ultrasonography in the post-menopausal period for the screening of endometrium pathology in women who are non symptomatic or undergoing hormone replacement therapy. A total of 152 women were examined, 76 were non-symptomatic and 76 were undergoing estro-progestational therapy. As in previous studies on the subject, we took 0.8 cm as the thickness limit for the endometrium; over this limit closer investigations are considered necessary. In the non-symptomatic women, a strong correlation between the thickness of the endometrium and hormonal state was noted; it was not possible to differentiate the proliferative-secretory endometrium from the hyperplastic one. For women under HRT ultrasonography proved to be a good method for monitoring the endometrium as it allows for an adequate evaluation of its thickness throughout the different phases of sequential hormone treatment. PMID- 7885613 TI - [Premature rupture of the membranes. Spontaneous course of the event and the therapeutic approach with a human fibrin glue]. AB - The results of the analysis of 47 cases of premature rupture of the membranes occurred between 20 and 35 weeks of gestation were reviewed. The aim is to evaluate the natural outcome of this pathology and the advantage of the endocervical application of a human fibrin glue (Tissucol) as a treatment of the cases of premature rupture between 20 and 27 weeks of gestation. This management has been performed at the Obstetric Department of the Universita de Verona since 1991 on a total of 5 cases. We demonstrated an evident prolongation of pregnancy leading as a consequence to an increased fetal survival rate. Actually the most important risk factor has to be identified in prematurity. PMID- 7885614 TI - [Screening for Salmonella in pregnancy]. AB - National and Regional Health Authorities advise a stool culture in pregnant women before term in order to detect Salmonella carriers, prevent the spread of this microorganism to the newborn and avoid outbreaks of this infection in the nurseries. The Tuscany section of the Italian Association of Obstetricians and Gynecologists decided to test the usefulness of this Salmonella screening. In 7431 pregnant women at the 36th week a stool sample was examined for the presence of Salmonella. The occurrence of diarrhoea in these women was also investigated. The prevalence of Salmonella excretors in our obstetric population was 0.27%. Thirty per cent of the positive women complained of diarrhoea; that means that the risk of being positive in the presence of this symptom is 11.8 times larger. The positive cases were detected essentially in late summer and fall. No nursery outbreak occurred during the period studied. The Salmonella-carrying mother can not take advantage of an effective antimicrobic therapy and a single stool sample allows the detection of only part of the carriers. Therefore screening can not prevent the possibility of transmission during birth. The unfavorable ratio between costs and benefits suggests that stool culture for Salmonella may be useful only in late summer and fall and in symptomatic women. In order to obtain better results in the prevention of infections among newborns the observance of careful hygienic rules in the delivery rooms and in the nurseries is mandatory. PMID- 7885615 TI - [Pap-smear test today]. AB - Remembering the publication of Papanicolau and Traut's monograph in 1943, the authors have realized the use and the spead of the Pap-Smear until the present. They have analyzed the different risks of cervical carcinoma. They think that to obtain a further reduction of the morbidity and the death-rate of such a neoplasia, it is necessary to do a pap-smear examination once a year for women with HPV infection or other risk factors. It is possible in this way, to improve results till the 90%. PMID- 7885616 TI - [Fetal diaphragmatic hernia. Clinical and prognostic considerations and early diagnosis]. AB - Fetal diaphragmatic hernia depends on a retarded closing during the first trimester of pregnancy of embryological structures in the chest that lead to the formation of diaphragmatic muscle. The defect occurs in form 1:2,000 to 1:5,000 livebirths and it is associated with other structural abnormalities (neural tube defects, cleft lip/palate, omphalocele, cardiopathy, etc). In 20% of cases it is associated with a chromosomal syndrome. Antenatal ultrasonic diagnosis has been reported, at 18-40 weeks of pregnancy. We describe a case of early diagnosis, at 17 weeks of pregnancy, of fetal diaphragmatic hernia by ultrasound. Plexus choroid cysts were detected too and fetal karyotyping resulted 47XX + 18. Prognosis of pregnancy in all cases of fetal diaphragmatic hernia is poor because fetal and neonatal losses are very heavy. PMID- 7885617 TI - [Extrauterine pregnancy in residual tube stump in a patient already treated with partial salpingectomy for right ampullar pregnancy. Report of a clinical case]. AB - The authors illustrate a case referred to their attention and underline the rarity of the extrauterine pregnancy described caused by the external migration of the fertilised egg which, passing through the contralateral tube and the uterus, became implanted in the residual tube stump (following earlier partial salpingectomy due to ampullar pregnancy). PMID- 7885619 TI - Intense sweeteners and the control of appetite. AB - The sensation of sweet taste without calories has been said to increase appetite and promote food consumption. Regular use of intense sweeteners might therefore lead to a paradoxical weight gain. These alarmist reports have not been confirmed by recent experimental data. There is no evidence that the addition of an intense sweetener to a plain stimulus promotes appetite or results in increased food consumption during some later meal. While replacing sugars with intense sweeteners (with attendant decrease in energy) has been said to result in energy compensation, published studies have variously reported perfect compensation, partial compensation, or no compensation at all, depending on the conditions used. Longer-term studies are needed to assess chronic effects of intense sweeteners on dietary compliance and the control of body weight. PMID- 7885618 TI - [Large pendulous fibroma of the vulva. A clinical case]. PMID- 7885620 TI - Reduced physical activity and its association with obesity. AB - The energy cost of daily physical activity was derived for 30 Pima Indians ages 19-71 using simultaneous measurements of total daily expenditure and basal metabolic rate in the free-living situation. The body fat of the subjects ranged from 10 to 45%. Weight-adjusted indexes of physical activity correlated negatively with percent body fat, reinforcing the hypothesis that obesity occurs with a lower level of physical activity. PMID- 7885622 TI - The diabetic diet: evidence for a new approach. AB - The dietary prescription for noninsulin-dependent diabetes mellitus remains an important component in the treatment of this disorder. Recent studies indicate that a diet high in monounsaturated fat and low in carbohydrate can produce a more desirable plasma glucose, lipid, and insulin profile. PMID- 7885621 TI - Sucrose permeability as a marker for nonsteroidal anti-inflammatory gastroduodenal injury: how sweet is it? AB - The authors report that sucrose is a novel permeability marker in the evalution of proximal gastrointestinal (GI) injury. In patients undergoing endoscopy and in volunteers who were chronically taking nonsteroidal anti-inflammatory drugs (NSAIDs), the sucrose permeability test accurately identified patients with severe gastritis and gastric ulcer. The sucrose permeability test did not detect other types of proximal GI injury as reliably. Given the propensity of NSAIDs to cause upper GI injury, the authors suggest that this test can be used to identify people who might be at high risk from the sequelae of NSAID ingestion. This interesting marker deserves further evaluation in targeted prospective studies. PMID- 7885624 TI - Myths & facts ... about asthma. PMID- 7885623 TI - Dietary advice: from folklore to present beliefs. AB - Many countries have folklore beliefs about the use of foodstuffs to remedy ill health and to promote long life. Many of the beliefs and practices of the ancients and, more recently, "mothers's views of health" have a basic soundness and are in harmony with present-day advice on the attainment of a prudent diet and life-style. PMID- 7885625 TI - Using nondrug interventions to relieve pain. PMID- 7885626 TI - Assessing an arteriovenous fistula. PMID- 7885627 TI - Preventing cervical cancer. PMID- 7885628 TI - Saying good-bye to Eric. PMID- 7885629 TI - When a patient refuses to cooperate. PMID- 7885630 TI - Evaluating glycosylated hemoglobin. PMID- 7885631 TI - Acute hyperglycemia: putting a lid on the crisis. PMID- 7885632 TI - Report on Jenni: positive progression. PMID- 7885633 TI - Acute hypoglycemia: keeping the bottom from falling out. PMID- 7885634 TI - Assessing chest pain. PMID- 7885635 TI - Close-up on opioid receptor subtypes. PMID- 7885636 TI - Passing the drug (error) test. PMID- 7885637 TI - Controlling phantom limb pain. PMID- 7885638 TI - Underwater chest drainage: bringing the facts to the surface. PMID- 7885640 TI - Depression & paranoia: Is your patient at risk? PMID- 7885639 TI - A gut feeling. PMID- 7885641 TI - Self-test: sharpening your neurologic nursing skills. PMID- 7885642 TI - Answering silent bells. PMID- 7885643 TI - Protecting your patient's wishes. PMID- 7885644 TI - Louise's first words. PMID- 7885645 TI - The management of perforated duodenal ulcer. PMID- 7885646 TI - Treatment of macroprolactinomas at Auckland Hospital 1975-91. AB - AIM: A retrospective review of management of patients with macroprolactinomas at Auckland Hospital 1974-93 to determine the efficacy of treatment. METHODS: Patients were identified from departmental patient disease index records and treatment outcome assessed. RESULTS: Thirty four patients (24 male, 10 female) were identified. The mean serum prolactin was 89,700mIU/L. Visual field defects were present in 20 and 24 were hypogonadal at presentation. Initial treatment was with bromocriptine (n = 24) or surgery (n = 7). Twelve medically treated patients were subsequently treated surgically (3 because of pituitary haemorrhage or infarction, nine because of slow or absent response to medication). Visual field improvement was similar in the medical and surgical groups and major treatment complications occurred in 3 of the medical and 3 of the surgical patients. Radiotherapy was given to 25 patients. Overall treatment responses over a mean follow up of 4 years were similar in surgically and medically treated patients. Overall only a third of patients had a normal serum prolactin at last follow up, pregnancy had occurred in 20% of potentially fertile patients and 35% were hypopituitary. CONCLUSIONS: Bromocriptine is a satisfactory first line treatment for macroprolactinomas, but although treatment reduces tumour size and reverses field defects in 75% of cases only one third of patients achieve a normal prolactin over medium term follow up. PMID- 7885647 TI - Peritonsillar infection in Christchurch 1990-2: microbiology and management. AB - AIM: To review the management and microbiology of peritonsillar infection in Christchurch. METHOD: The hospital records of patients admitted acutely to Christchurch Hospital with peritonsillar infection between January 1990 and December 1992, were reviewed. RESULTS: 109 patients were admitted with peritonsillar infection, of which 74 (68%) were found to have a peritonsillar abscess. Of these 74, needle aspiration was performed in 22, incision and drainage in 15, both aspiration and drainage in 31, and acute tonsillectomy in 6. Interval tonsillectomy was performed in 35 patients. Sixteen pathogenic bacterial groups or species were cultured from 39 aspirates. Of the total number of bacteria isolates, obligate anaerobes were cultured in 48%, and group A beta haemolytic streptococci in 29%, while aerobic beta-lactamase producing bacteria were cultured in only 6%. CONCLUSION: Central to the management of peritonsillar abscess is drainage. This was commonly achieved by needle aspiration and/or incision. As beta-lactamase producing organisms are infrequent, penicillin remains the antibiotic of choice. Metronidazole may be required in a non responding patient, particularly if resistant anaerobes are cultured. PMID- 7885648 TI - Management of hypertension and the core services guidelines: results from interviews with 100 Auckland general practitioners. AB - AIM: To determine if the management of a hypothetical case of essential hypertension by general practitioners conforms with the Report to the National Advisory Committee on Core Health and Disability Services guidelines on the Management of Raised Blood Pressure in New Zealand (Core Services Report on Hypertension) sent to all general practitioners in November 1992. METHOD: A cross sectional survey of a random sample of 100 Auckland general practitioners using a standard case of a 60 year old man with essential hypertension. Seventy interviews were conducted by a face-to-face interview and 30 by telephone interview. The main outcome measures were. Initial choice of medication and levels at which blood pressure would require treatment. RESULTS: Forty one percent of the interviewed doctors had read the Core Services report on hypertension. Fifty percent of the doctors indicated they would use the recommended first line antihypertensive medication (ie, diuretic or beta blocker). Doctors who prescribed beta blockers had been graduated a significantly longer time than those who did not. The majority of doctors indicated that they would initiate pharmacological treatment at lower blood pressures in younger patients than older patients contrary to the recommendation of the report. CONCLUSIONS: Current reported practice is only partially consistent with that suggested by the Core Services report on hypertension. Approximately half of the doctors interviewed were prescribing the recommended first line medication. Treatment was more likely to be initiated at lower levels in younger patients than in older patients in spite of the higher absolute risk and potential absolute benefit in the latter group. Adherence to the guidelines could see a shift from overtreatment of younger patients to an increase in treatment for older patients who are at higher risk of blood pressure related disease. More specific graduate educational measures will be needed if the Core Services report on hypertension are to be implemented. PMID- 7885649 TI - The detection of postnatal depression in general practice using the Edinburgh postnatal depression scale. AB - AIM: To determine how many women with postnatal depression were detected with the Edinburgh postnatal depression scale at the 6 week postnatal examination. METHOD: One hundred and twenty-one women attending this general practice for their six week postnatal examination completed the Edinburgh postnatal depression scale (EPDS); a score of greater than 12.5 was used to predict the likelihood of postnatal depression. Postnatal depression was defined as a major depressive illness according to the DSM III criteria, occurring in the 12 months following delivery. RESULTS: Seven women had postnatal depression and six of these women scored over 12.5 with the EPDS. Eight women had other depressive disorders (depressive disorders that did not reach DSM III criteria) and five of these scored over 12.5. Those scoring over 12.5 had a 64% risk of having some form of depressive disorder. Those scoring under 12.5 had only a 4% risk of postnatal depressive disorder. (1% risk of postnatal depression and 3% risk of other depression). CONCLUSION: The EPDS is an easily completed and well accepted 5 minute questionnaire which reliably identified most women with postnatal depression and other depressive disorders in this general practice. PMID- 7885650 TI - Infant feeding patterns in Canterbury. AB - AIM: To examine infant feeding patterns during the first 6 months of life in Canterbury. METHODS: A random sample of 10% of all births over a 12 month period in Canterbury was taken from birth notifications (n = 520). Information on the type of feeding was recorded prospectively at three time periods and extracted from available Plunket nursing notes. The participation rate was 81%. Data from nonparticipants on the method of feeding at discharge was obtained from obstetric records. RESULTS: Overall, 90.7% were breastfed at discharge. There was no difference between breastfeeding rates of the participants (91%) compared to the nonparticipants. For participants, 88% were exclusively breastfed at discharge which steadily declined to 36% at 24 weeks. However, some breastmilk was still being given to 70% at 24 weeks. CONCLUSION: Breastfeeding rates are good in comparison to other nations. However, there is room for improvement particularly maintaining exclusive breastfeeding to at least four months. This could be stimulated by the Baby Friendly Hospital Initiative and the fostering of a baby friendly environment to further support and promote breastfeeding in the community. PMID- 7885651 TI - A new method of infant monitoring: for use at home and hospital. AB - AIM: To test a New Zealand originated, designed and funded remote infant heart rate monitor in the home and hospital settings (temporarily named the King Monitor) for accuracy and reliability. METHODS: The units were pretested using ECG simulators and on infants already being monitored in the neonatal unit. Longer term trials on hospital infants and infants being simultaneously monitored at home were then conducted. RESULTS: Interference and electrode problems were corrected during the pretesting phase. The unit worked accurately when compared with the standard neonatal heart and respiratory rate monitor in hospital and appeared in some infants to give earlier warning of problems than the standard home apnoea monitor. CONCLUSION: This simple to use monitor worked reliably and accurately under a wide variety of settings and with varying sized infants. In addition, the lack of direct connection between the infant and the control unit allowed freedom of movement of normal infants around the cot or bassinet. The monitor will require to be adapted for portable use at home and during travel. PMID- 7885652 TI - Fatal smothering by a domestic cat. PMID- 7885653 TI - Diagnosis related groups based funding and medical care of the elderly: a form of elder abuse? PMID- 7885654 TI - Professor Jan Bokhman says... (or why we forget about clinical empiricism at our peril) PMID- 7885655 TI - Episiotomy: risks of dehiscence and rectovaginal fistula. AB - The obstetric literature was reviewed to assess the risk of episiotomy dehiscence and rectovaginal fistula formation from routine episiotomy, with and without third- and fourth-degree laceration into the rectal sphincter or rectal mucosa, respectively. Strong evidence suggests that elective episiotomy predisposes to severe 3rd and 4th degree perineal lacerations and that episiotomy dehiscence with rectovaginal fistula formation is strongly related to 3rd and 4th degree perineal lacerations. PMID- 7885656 TI - Bacterial vaginosis: drugs versus alternative treatment. AB - Bacterial vaginosis is one of the most common infectious disorders affecting women. It is caused by several microorganisms, including Gardnerella vaginalis, Bacteroides, beta-streptococci and mobiluncus/falcivibrio sp. Bacterial vaginosis is thought to occur as a result of a change in vaginal pH mediated by the metabolic activity of anaerobic bacteria. This rise in vaginal pH interferes with the activity of vaginal lactobacilli which maintain vaginal acidity. Several types of antibiotics have been used to treat this condition. Although metronidazole was found to be the most effective, none was completely successful in either cure or prevention. Several attempts have recently been made to treat bacterial vaginosis using physiological or 'natural' substances, such as lactate gel and commercial yoghurt, which is acidic and also contains lactobacillus strains. This kind of treatment looks promising and may have a place in certain clinical conditions, including pregnancy, in cases of recurrent inflammation, or as a prophylactic treatment before invasive gynecological procedures or abdominal surgery in patients known to be affected. This issue should be additionally studied and evaluated in light of the relatively little experience with this modality of treatment for bacterial vaginosis. PMID- 7885657 TI - Guidelines for surgical staging of ovarian cancer. PMID- 7885658 TI - Is peritoneal closure necessary? AB - Closure of peritoneal defects after laparotomy has long been considered a standard surgical procedure. In 1895 Smith wrote that "Sinister results which we seek to avoid, arise when we leave raw surfaces to which intestines may adhere and cause obstruction. To cover such a surface by peritoneum would, according to published statistics, save nearly 2 percent of the deaths after abdominal operation." (1). The purpose of this review is to reexamine the necessity of peritoneal closure in current medical practice. The argument for peritoneal closure includes the following: 1) restoration of anatomy and approximation of tissues for healing, 2) reestablish the peritoneal barrier to reduce the risk of infection, 3) reduce the risk of wound herniation or dehiscence, and 4) minimize adhesion formation. The argument against peritoneal closure involves the following: 1) nonclosure has not been observed to be detrimental, 2) without reapproximation the peritoneum heals rapidly, 3) suture presence and additional tissue handling may contribute to adhesion formation and 4) reduced surgical intervention and operating time is beneficial to the patient. This review will individually discuss these arguments and summarize their relative support. PMID- 7885659 TI - Postmenopausal tamoxifen treatment and endometrial pathology. AB - Tamoxifen is widely used as adjuvant therapy for postmenopausal breast cancer patients with positive estrogen receptors. Data on a possible association of endometrial pathologies with tamoxifen treatment have been accumulating. In this review, we examine the current literature and include our own experience with this occurrence. We recommend close supervision of these patients. PMID- 7885660 TI - Renal hemodynamics and volume homeostasis in pregnancy. AB - Maternal hemodynamic adaptation to pregnancy consists of profound changes in various interdependent systems. Of crucial importance in the early adaptation of the volume homeostatic mechanisms to pregnancy is the resetting of the volume and osmoreceptors. This resetting may be induced by a reduction in vascular tone and leads to early changes in plasma osmolality and glomerular filtration rate. After this initial adaptation other volume-regulating mechanisms such as the renin angiotensin-aldosterone system, pregnancy hormones, and alpha-ANP adapt to the rising blood volume. The initial adaptation results in a state of relative vascular underfill, inducing secondary compensations in the volume homeostasis. The initially increased vascular capacitance in pregnancy is compatible with the signals of vascular overfill. Contrarily, the protracted filling of this enlarged vascular bed triggers signals compatible with vascular underfill. PMID- 7885662 TI - Statutory right of access to OH services. PMID- 7885661 TI - Vesicovaginal fistula. AB - Vesicovaginal fistulas are often the result of obstetric trauma in third world countries and gynecologic surgery in developed countries. Improvement in obstetric care and the increased use of cesarean section has resulted in a decrease in the incidence of obstetric fistulas in the United States. However, the incidence of fistulas as a result of surgery has remained relatively unchanged for years. Most postoperative fistulas occur under very normal operative circumstances. The keys to prevention of postoperative fistulas are wide dissection of the bladder from the cervix and vagina in the correct plane during surgery and recognition of bladder damage intraoperatively with appropriate repair. More than 90 percent of vesicovaginal fistulas can and should be repaired vaginally. The procedures available for repair are the flap splitting and Latzko techniques. On occasion an abdominal approach is indicated, particularly for vesicouterine fistulas. Requirements for successful repair include adequate surgical exposure, wide mobilization of the vagina, nonexcision of the fistula tract, tension-free closure of the bladder, and grafting when indicated. PMID- 7885663 TI - Working towards wellness. PMID- 7885665 TI - Food, glorious food. PMID- 7885664 TI - Capacity assessment in the workplace: a new step test. PMID- 7885666 TI - Statutory right of access to OH services. Part 2. PMID- 7885667 TI - Drug and alcohol screening in the workplace. PMID- 7885668 TI - Imagery, self-esteem and laughter. PMID- 7885669 TI - Stress and the law. PMID- 7885670 TI - Corneal abrasion associated with contact lens correction of keratoconus--a retrospective study. AB - BACKGROUND: Corneal abrasion is a frequently encountered complication of contact lens wear, but we are not aware of any previous study of relative frequency comparing keratoconic to nonkeratoconic patients. METHODS: We retrospectively studied the incidence of corneal abrasion during 2 months of contact lens practice. RESULTS: 784 contact lens-related patient visits (494 total patients); patients were assessed by 3 optometrists and 13 abrasions (11 patients) were diagnosed. Only the total number of individual patients and the first abrasion for each patient were statistically considered; the overall frequency of abrasion was therefore 11/494 (2.3%)/2 months. The frequency of abrasion was 5/68 (7.4%)/2 months for keratoconic patients and 6/426 (1.4%)/2 months for nonkeratoconic patients and this difference was significant (chi 2 test: p < 0.01). Among nonkeratoconic patients, the frequency of abrasion was 2/246 (0.8%)/2 months with hydrogel contact lens wear and 4/178 (2.2%)/2 months with rigid gas permeable (RGP) contact lens wear, but this difference did not achieve significance (chi 2 test: p = 0.10). IDENTIFIED RISK FACTORS INCLUDED: Contact lens wear; a torn lens and chemical keratitis for hydrogel lens wearers; an adherent "bound" lens and keratoconus for rigid lens wearers. CONCLUSION: Keratoconus appears to be a statistically significant risk factor for corneal abrasion among contact lens wearers. PMID- 7885671 TI - Exercise does not increase visual field sensitivity. AB - The effect of exercise on visual field sensitivity was investigated for both static and kinetic visual fields using the Humphrey Field Analyser (HFA). The visual fields of 20 young visually normal subjects were measured before and after a 10-min controlled period of exercise. Ten of these 20 subjects then formed a control group, where the same experimental regime was followed without the exercise period. A significant increase in mean static sensitivity in the superior field was found as a result of exercise; however, this is likely to be a learning effect as a similar increase was also found for the control condition. Exercise had no other effect on either the kinetic or static visual fields. PMID- 7885672 TI - Luminance effects on visual acuity and small letter contrast sensitivity. AB - The purpose of this study was to evaluate the effects of luminance on visual acuity (VA) and small letter contrast sensitivity (SLCS). Computer-generated letter charts were used to measure VA and SLCS [6/7.5 (20/25) Snellen equivalent] as a function of stimulus luminance. Letter size (VA) and contrast (SLCS) were varied in equal logarithmic steps, making the task and scoring procedure comparable for the two types of measurement. Both VA and SLCS decreased with decreasing luminance, but the effect was far greater in the contrast domain. Reducing luminance from 116 cd/m2 to 0.23 cd/m2 produced a 3 x reduction in VA, but a 17 x reduction in SLCS. The greater sensitivity of SLCS to luminance endured even after correction for greater measurement variability. SLCS is a sensitive approach for detecting resolution loss undisclosed by standard measures of VA. It may be useful for monitoring visual loss from light attenuation in early cataracts, and for detecting subtle resolution loss from neural or pathologic factors in ocular and neuro-ophthalmologic disease. PMID- 7885673 TI - Low vision magnifiers--their optical parameters and methods for prescribing. AB - Information provided by manufacturers of low vision magnifiers is usually insufficient to allow the clinician to predict accurately the resolution improvement that patients may be expected to achieve. We have measured and tabulated the key optical parameters of 92 stand magnifiers and 53 hand-held magnifiers. For the fixed focus stand magnifiers, the image location and the equivalent power of the lens system have been determined and the enlargement ratio has been derived. For each magnifier, 3 different eye-to-lens distances (2.5, 10, and 25 cm) have been considered and, for each of these, the Equivalent Viewing Distance (EVD), the eye-to-image distance, and the theoretically predicted field width have been computed. The EVD is useful in predicting resolution performance because, for a given patient, the visual resolution limit will be directly proportional to the EVD. The eye-to-image distances allow the clinician to consider whether the patient will be in satisfactory focus or whether adjustments need to be made to the power of any reading addition. The stand magnifiers are listed in order of the EVD they give when the eye is a moderate (10 cm) distance from the magnifier. For the hand-held magnifiers, the equivalent powers have been measured. The EVD for a hand-held magnifier will be the same as the equivalent focal length of the magnifier if the lens is used so that the image is at or close to infinity. The tables include supplementary information on the size of the magnifier lenses and whether the magnifiers incorporate battery, electric, incandescent, or halogen lighting systems. Examples are presented to illustrate how the tables might be used in the selection of magnifiers to meet the resolution and other needs of individual patients. PMID- 7885674 TI - Critical subjective measurement of amplitude of accommodation. AB - The use of fixed print size to measure amplitude of accommodation by the push-up method will result in a range of angular sizes of the print at the nearpoint for patients with different amplitudes. We investigated the effect of this on measured amplitude of accommodation in 60 subjects aged 25 to 45 years. We designed a near-vision chart, based on the Bailey-Lovie near-vision charts, but for which the letter sizes on adjacent lines are varied so that the difference between the inverse of letter sizes is constant (dioptric scale) rather than the geometric ratio between letters on adjacent lines being constant (logarithmic scale). Using this new chart, we compared the amplitudes obtained using N5 print (N5 Blur method) and with two critical methods for which the print of interest was always close to threshold acuity. This was achieved by having patients' attention drawn to a smaller line of letters every time the chart was moved closer in half-diopter steps. The N5 Blur method gave considerably higher amplitude measures than the two critical methods, but the mean differences decreased markedly as age increased: 1.8 to 2.2 D for a 25- to 29-year-old group to 0.7 to 0.8 D for a 40- to 45-year-old group. We believe that the use of fixed size print for measuring amplitude of accommodation by the push-up method gives overestimations that are more marked the higher the amplitude. This occurs because smaller measuring distances that accompany the higher amplitudes will increase angular size and consequently depth-of-focus (in dioptric terms).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885675 TI - The association of headache and monocular blur effect in a clinical population. AB - PURPOSE: Because some headaches are known to be associated with errors in binocular vision and because monocular visual acuity has been observed to change in different directions of gaze during binocular viewing, a study was designed to see if headaches were associated with this phenomenon. METHOD: This cross sectional study cross-classifies each subject in a sample selected in consecutive order from an optometric practice by whether or not the patient has at least three headaches per month and by whether or not the patient has the monocular blur effect. Each of the two examiners conducted this cross-classification separately on the same sample. The laterality of the headache and the side which exhibited the monocular blur effect were also noted. RESULTS: The resulting two way tables are presented along with the results of the chi 2 tests. The results are statistically significant. CONCLUSION: It appears that a relation exists between the occurrence of headache and binocular vision anomalies associated with the action of the eye muscles. The extraocular muscles and relevant neurological and vascular physiology are discussed as they relate to headache. PMID- 7885676 TI - Seminar report: optometric management of the excimer PRK patient. Joe Barr, course director. PMID- 7885677 TI - [Life-threatening arrhythmia treated by an implantable defibrillator]. PMID- 7885678 TI - [Fetal blood circulation in multiple pregnancy]. AB - Blood flow velocity waveforms in maternal uterine and fetal umbilical, middle cerebral and renal arteries were studied utilizing color coded pulsed Doppler ultrasound in 31 twin and 3 triplet gestations during the last trimester. Thirty one (45.6%) out of 68 neonates were born with appropriate body weight for gestational age. Thirty-seven (54.4%) babies were small for gestational age. Of the last mentioned 37 infants 15 were small as a result of placental insufficiency. The remaining 22 babies were growth retarded due to other causes. Their resistance indices were slightly higher than in the controls in all of the investigated blood vessels. In the group of growth retarded babies due to placental insufficiency, the resistance indices of the umbilical arteries were significantly higher than those of controls (0.77 +/- 0.19 vs. 0.61 +/- 0.04). In contrast the resistance index values of the middle cerebral arteries were lower (0.70 +/- 0.05 vs. 0.79 +/- 0.11). The authors conclude that these data indicate brain sparing effect associated with placental insufficiency both in concordant and discordant growth retarded twins and triplets. This phenomenon is similar to the blood flow redistribution that occurs in growth retarded singletons in connection with placental insufficiency. PMID- 7885680 TI - [Implantable pacemaker-cardioconverter-defibrillator]. AB - The aim of this article is to introduce the automatic, implantable cardioverter defibrillator (AICD) device in connection with the first two cases in Hungary. At present time, the indications of the AICD implantation in the European Community are as follows: recurrent sustained episodes of ventricular tachycardia ventricular fibrillation or aborted sudden cardiac (arrhythmic) death, when the treatment of the underlying heart disease and/or the application of antiarrhythmic drugs, antitachycardia surgery (or catheter ablation procedures) proved to be unsuccessful in the prevention of the ventricular tachyarrhythmias (guided by serial intracardiac electrophysiologic testing and exercise testing), Holter monitoring. On the one hand the implantation of an AICD is not a causative treatment, on the other hand the cost of an AICD is extremely expensive. On the 8th of January, 1992, the first AICD (PCD Medtronic 7217B) implantation was performed in the Hungarian Institute of Cardiology. At the first patient with dilatative cardiomyopathy, the cardioverter defibrillator discharged successfully at 16 times. Unfortunately, the implantation of this patient with AICD could prolong his life only with months due to the rapid progression of the underlying cardiomyopathy. The second patient with AICD implantation went home after the uneventful surgery. The implanted cardioverter defibrillator unit worked properly, spontaneous ventricular tachycardia was terminated successfully. The AICD treatment considerably decreases the risk of sudden cardiac (arrhythmic) deaths. PMID- 7885679 TI - [Method for the determination of the functional degree of esophageal stricture and the effectiveness of dilatation]. AB - Based on their experiences of 494 oesophagus dilatation in 98 patients, authors developed a stadium system for defining the severity of dysphagia caused by oesophagus stenosis of stricture. This system is usable for follow-up the course of the disease, for the establishing the necessity of the dilatation, and for the comparison of results achieved by different dilatation methods, as well. The method is based on simple, well-defined clinical parameters, special skills or instrumentations not required, and fits the clinical experiences of many years of the authors. For this reasons it is useful both general practitioners and for the specialists performing the esophagus dilatation, as well. PMID- 7885681 TI - [Experience with a transvenous pacemaker-cardioconverter-defibrillator without subcutaneous patch]. AB - Sudden cardiac death caused by malignant ventricular arrhythmias is one of the main causes of cardiovascular mortality. Implantation of cardioverter defibrillators has resulted in the reduction of the incidence of sudden cardiac death caused by malignant ventricular arrhythmias from the yearly 10-30% to 1%. For the very first time in Hungary, the authors applied only transvenous lead configuration for automatic cardioverter defibrillators in three patients. The indications of the implantation were ventricular fibrillation in one case, ventricular tachycardias refractory to drug treatment in two cases. Ventricular arrhythmias were secondary to coronary heart disease in two patients, dilatative cardiomyopathy in one patient. Preoperative, intraoperative and postoperative electrophysiological studies were regularly taken. Using Biotronik Phylax 03 device with a right ventricular electrode and a superior vena cava electrode and without subcutaneous patch the intraoperative defibrillation thresholds were 6, 11 and 12 J respectively. The fractally iridium coating increases the surface of the electrodes that has a very good effect on defibrillation threshold. During a mean follow-up of six months the occurring spontaneous ventricular arrhythmias (1 ventricular fibrillation and 5 ventricular tachycardias) were terminated by Phylax 03 with cardioversion-defibrillation or overdrive stimulation. The authors' results of intraoperative testing and clinical experiences show that the Phylax 03 biphasic system due to low defibrillation thresholds without subcutaneous patch can safely be applied with only transvenous implant technique in patients with major ventricular arrhythmias to prevent sudden cardiac death and to terminate ventricular tachycardia. PMID- 7885683 TI - [History of the Obstetric-Gynecologic Department of the Szent Margit Hospital]. PMID- 7885682 TI - [Question marks in the biography of Istvan Weszpremi]. PMID- 7885684 TI - [Bone and joint tuberculosis in Hungary today]. AB - Authors introduce to the history of efforts against tuberculosis in Hungary. The effectiveness of this figh is shown by the decrease of morbidity rates. The decrease of morbidity rates was followed by the cutting down of the system of institutions devoted to the conquest of tuberculosis. Authors give account on the present epidemiological conditions and report on the four and a half years activity of their bone and joint surgery department in this field. The department proved to be reliably suitable for the treatment of patients with bone and joint tuberculosis. They draw the attention to the significance of yearly 30 cases which show that the tuberculosis did not yet disappear from Hungary. The aim of the paper is to maintain the problem in the common medical consciousness. PMID- 7885685 TI - [Transient neonatal myasthenia gravis]. AB - Authors reported about their experiences with newborn infants, who had transient myasthenia gravis; one disease developed in the fetal, others 10 in the early neonatal age. Direct correlation was found between the development of maternal polyhydramnios and the severity symptoms in newborns: risk of neonatal myasthenia gravis increased at these infants. Specific treatment included blood exchange transfusions and pyridostigmin (Mestinon) medication for 2-10 weeks. Five transient myasthenia gravis responded readily to blood exchange transfusions. Authors pointed out that in the early neonatal period the aetiology of an obscure respiratory inadequacy and hypoventilation might be regarded as transient myasthenia gravis. PMID- 7885686 TI - [Role and potentials of the pathologist in modern clinical gastroenterology. In memory of Prof. Geza Hetenyi]. AB - In the course of memorial lecture the author commemorates Professor Geza Hetenyi. His synthetizering role is stressed, analysing the professor's views on the clinical and theoretical medicine, on the medical practice and teaching in the medicine. Author performs it from the points of view of practising pathologist who considered the clinical pathology as the most important. After these introductory thoughts the role of pathologist is outlined in the gastroenterological diagnostics. Before the introduction of modern fiberoptic endoscopy, the pathologist met with some forms of the gastroenterological diseases at most during the processing work of surgically removed specimens or even more in the autopsy room, but in the latter cases only their end stage could be demonstrated. The introduction of so-called blind exfoliative cytology by the gastric lavage was a great leap forward. Advanced gastric carcinoma were detected mostly by this method but some early gastric cancer could be also discovered occasionally. The more and more wide-spread use of modern fiberpotic endoscopy was of decisive importance because by this way the aimed forceps biopsy could be performed completed with a new form of gastric cytology, with abrasive smears. The specificity and sensitivity of the latter method achieves or surpasses the 90%. Nowadays, not only the stomach carcinomas but their possible precancerous conditions and changes as chronic gastritis can be diagnosed on morphological basis. The history of different gastritis classifications is also surveyed emphasised author's own pathogenetic conceptions which can be included well in our now accepted modern Sydney-classification.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885687 TI - [Clinical comparison of two topical antiviral ointments in herpes]. AB - Herpetic skin lesions have importance and growing frequency in the population. The authors report a double blind study involving 51 patients suffering from recurrent labial herpes to compare the effectiveness and adverse reactions of two topical antiviral preparations, the aciclovir (Zovirax) and epervudine (Hevizos). There was no significant difference between the two treatment groups in the healing tendency of herpetic lesions. The rate of relapses in a two months period was 44.4% in the group treated with aciclovir and 20.8% in the group treated with epervudine, the difference is not significant. Both preparation was well tolerated, only itching occurred as adverse reaction in the group treated with aciclovir. According to the results of the study the original Hungarian product (Hevizos), is at least as effective as the other topical preparation. PMID- 7885689 TI - [Neonatal splenic cyst]. AB - The author found five splenic cysts during ultrasound newborn screening. The size of cysts were between 5 and 11 mm. One of them slowly arised from 7 to 11 mm during 9 months. The other four held spontaneously. There were no cyst in other abdominal organs. The author could observe the process of healing in two cases: the size of cysts did not altered but in the inside of the cysts seemed the echopoor structure of the spleen. Later the site of the cysts were not visible more. The author saw similar splenic cysts in a four and a five years old children. The first was more time investigated in his first year of life with ultrasound by the author and no cyst was visible in his spleen. The etiology is not known but the accumulation of cases in time and space refer to an infective origin. PMID- 7885688 TI - [Follow up of patients with prostatic cancer after radical prostatectomy: results, late complication, survival rate]. AB - The authors performed radical prostatectomy on 35 prostate cancer patients between 1986 and 1991. At the end of 1993 the authors were informed about 25 patients. The mean follow-up was 4.4. years. Two patients have died in tumour related diseases, one in intercurrent diseases. In six patients progression was observed. Five patients had to operated because of anastomosis stricture. One patient was operated because of total incontinence another one uses penis clamp. PMID- 7885690 TI - [Can something new be said about Paracelsus?]. PMID- 7885691 TI - [Attitude, inflation, unavailability or interest, costs and organization. Thoughts on steroid receptors and growth factors]. PMID- 7885692 TI - The neurocutaneous free fibula flap in mandibular reconstruction. AB - Despite the delayed application of the free fibula flap to mandibular reconstruction, its recognition as a reliable, sensate skin paddle combined with enough bone to repair any mandibular defect and offer bicortical fixation of osseointegrated implants has proved the free fibula flap to be a "workhorse" in the repair of composite mandibular defects. The low donor site morbidity slightly eases the wait for the molecular reconstructive "cocktails" from the shelf of the next millennium. PMID- 7885693 TI - The iliac crest composite flap for oromandibular reconstruction. AB - Reconstruction of oromandibular defects following tumor ablation remains a complex endeavor. Its outcome greatly influences a cancer patient's quality of life and ability to become re-integrated into society. The number and variety of reconstructive options attest to the complexity of the problem and to the failure of any one method to demonstrate its superiority. We have favored the iliac crest internal oblique free flap because of the quality of the bone and flexibility of the soft tissues. These qualities make this flap the ideal option for reconstruction of through-and-through defects of the oral cavity. Our experience reveals that this flap is highly successful in restoring functional mastication in most patients and is associated with minimal donor site morbidity. It is important to recognize, however, that it represents one of many available techniques for the reconstruction of composite oral mandibular defects. PMID- 7885694 TI - Radial forearm flaps. AB - Restoration of oral cavity and pharyngeal function following ablative surgery remains an elusive goal. Conventional reconstructive methods often achieve satisfactory wound healing, but the introduction of a dynamic anesthetic and bulky flaps into the oral cavity can interfere with the function of the residual soft tissues. This article examines the anatomy, harvest technique, and applicability of neurosensory radial forearm flaps to head and neck reconstruction with special attention to the attributes of this donor site which, at present, make the radial forearm flap the flap of choice for the reconstruction of a variety of oral cavity and pharyngeal defects. PMID- 7885695 TI - Free tissue transfer in oromandibular reconstruction. Necessity or extravagance? AB - The challenges of oromandibular reconstruction have spawned tremendous progress and controversy in recent years. Foremost has been the development of free-tissue transfer. The selection of autogenous composite grafts whose volume and features closely approximate those of the ablative defect seems attractive, but are free flaps for everybody? This article defines the goals of the elusive "ideal" oromandibular restorative technique and compares the numerous options available to today's surgeon. PMID- 7885697 TI - The jejunal free flap in oral cavity and pharyngeal reconstruction. AB - The jejunal free flap is comprehensively reviewed in this article. Information on the historical development, the anatomy and physiology of the jejunum flap, and the particular suitability of this donor site for creation of free-tissue units is described. The correct abdominal harvest and vascular anastomosis techniques are also reviewed. A detailed description of how jejunal free flaps are placed into the oral cavity and oropharynx is then provided with particular reference to the split jejunal flap and its disposition in these recipient sites. It is concluded that this flap continues to maintain an already well developed place in the armamentarium of the head and neck reconstructive surgeon. PMID- 7885696 TI - Options for reconstruction of the pharyngoesophageal defect. AB - Reconstruction of the circumferential pharyngoesophageal defect and functional rehabilitation of swallowing after cancer ablation remain a challenge for head and neck surgeons. A variety of techniques have been described, four of which have particular merit. The following general guidelines can be utilized when selecting a reconstructive technique. The pectoralis major myocutaneous flap can be used when pharyngeal mucosa remains following cancer resection or by surgeons who do not perform microvascular free tissue transfer to reconstruct circumferential defects. Gastric pull-up should be used if significant extension of tumor into the esophagus is present, oncologically necessitating esophagectomy. Free jejunal flaps are particularly useful in obese patients or patients in whom the lateral cutaneous thigh flap is otherwise contraindicated. The lateral thigh flap gives excellent results, has low morbidity, and causes virtually no functional impairment at the donor site. We believe that it represents state of the art in pharyngoesophageal reconstruction. PMID- 7885698 TI - Lateral thigh flap. AB - The lateral thigh flap is a fasciocutaneous flap from the lower limb that can be a versatile and reliable alternative in the reconstruction of specific head and neck defects. This article discusses the anatomy, clinical applications, advantages, and disadvantages of the lateral thigh flap. PMID- 7885699 TI - Free flap transfer for restoration of sensation and lubrication to the reconstructed oral cavity and pharynx. AB - The reconstruction of defects of the oral cavity and pharynx, whether created by trauma or by tumor ablation, begins with a careful assessment of the patient and the defect. Ideally, it ends with the successful execution of the reconstructive surgical procedure that optimally restores form and function to the patient. The modern head and neck reconstructive surgeon must be adept at performing all reconstructive options in order to objectively choose among the many grafts and flaps now available. This article attempts to guide the surgeon in selecting the most appropriate surgical tool to best restore defects of the oral cavity and pharynx. PMID- 7885700 TI - Postoperative monitoring and salvage of microvascular free flaps. AB - We believe that it is essential to closely monitor the viability of any free flap in order to decrease potential morbidity to the patient. A myriad of techniques have been described, many of which appear quite promising; none has been widely accepted. We believe that clinical assessment of an exposed portion of a free flap is the most reliable method of postoperative "surveillance"; however, continuous observation by the surgeon is impractical. Other monitoring techniques, such as laser-Doppler flowmetry, allow nursing personnel to observe the patient in order to alert the surgeon at the first sign of trouble. Adjunctive monitoring techniques are currently imperfect and, in general, expensive. The cost must be measured, however, against the potential loss of a flap and its subsequent consequences. Until an "ideal" monitoring technique becomes available, a combination of some of the techniques described here will enable the surgeon to maximize the chances of salvaging a failing flap. PMID- 7885701 TI - Bad news and very bad news. PMID- 7885702 TI - Physicians should control PHOs. PMID- 7885703 TI - Busy legislative session ends on quiet note. PMID- 7885704 TI - Form follows function. PMID- 7885705 TI - Implementing a membership-driven process: medicine's future is in your hands. PMID- 7885706 TI - Let's hear it for sharper listening. PMID- 7885707 TI - The great health system reform myths of the 1990s. AMA Center for Health Policy Research. PMID- 7885708 TI - Hantavirus pulmonary syndrome is here. PMID- 7885709 TI - Another new language to learn. PMID- 7885710 TI - Why the health care system is broken. PMID- 7885711 TI - Keep a watchful eye in '95. PMID- 7885712 TI - Epidemiology of spinal cord injuries: a reflection of changes in South African society. AB - The records of all patients (492 males and 124 females) admitted into a spinal rehabilitation programme over a period of 6 years were reviewed. Most of the patients were in the age group 20-29 years and trauma accounted for 89% of all spinal cord lesions. Gunshot injuries were the commonest (36%), followed by injuries related to motor vehicle accidents (MVA) (25%), stab wounds (20%) and falls from heights (2.4%). Aetiological patterns changed over the 6 year period covered: gunshot injuries increased markedly and stab wounds decreased in number. The records of a medico-legal laboratory in the same geographic region revealed the same trend. Neurological recovery rates were better in patients with stab wounds and nontraumatic lesions than in those with MVA-related injuries and gunshot wounds. When compared to similar studies from other countries, our results show a disproportionately high incidence of violent injuries, particularly gunshot wounds, in South African plegic patients. We concluded that the recent sociopolitical changes and especially the general escalation of violence in the country, is reflected in the observed changes in the epidemiology of spinal cord injuries. PMID- 7885713 TI - Epidemiology of spinal injuries in Romania. AB - Retrospective and prospective epidemiological studies in Bucharest indicated a high rate of spinal injuries (about 28.5 per million population per year) in Romania. Most patients were poor, male, manual workers. Half of them were aged less than 40. Falls, particularly from horse-drawn carts, and road traffic accidents were the most frequent causes of injury. In summer, diving accidents were a common cause of spinal injuries. Sixty per cent of the patients had cervical injuries. Pressure sores became less frequent as staff and relatives were trained to turn and position patients. Because gastroduodenal bleeding and deep vein thrombosis were rare, the systematic use of drugs to prevent these conditions was deemed to be unnecessary, given the financial constraints. A shortage of beds and facilities made it difficult to manage associated injuries in a neurosurgical clinic in Bucharest or to admit all patients for rehabilitation. Thirty-nine per cent of all patients admitted with spinal injuries had spinal surgery (61% of those with neurological impairment). Bone grafting was the most common procedure for cervical injuries; surgical stabilisation was not commonly performed due to the shortage of plates and screws. The mortality rate in the early days post injury decreased from 22% (1985 1991) to 10.1% (1992) as medical management improved and the relatives helped with care in the acute phase. A programme is needed in Romania to prevent the accidents that cause spinal injuries and to improve clinical management. As a result of this study, three films were made to aid the prevention of accidents and to train staff and relatives in the care of those with spinal cord injuries. PMID- 7885714 TI - Post-traumatic syringomyelia: a review of the literature. AB - The need for increased awareness and a high index of suspicion for post traumatic syringomyelia is emphasised. Early clinical diagnosis confirmed by MRI and early treatment can avert or minimise the potentially devastating effects of post traumatic syringomyelia. The regular and frequent follow up of the patient on a yearly or alternate year basis to monitor the patient with spinal injury for this complication, as well as other complications, is the best way to ensure that post traumatic syringomyelia is diagnosed and managed early in order to avoid further disability. PMID- 7885715 TI - The prevention of spread of methicillin resistant Staphylococcus aureus in a spinal injuries centre. AB - The National Spinal Injuries Centre (NSIC) is a tertiary referral centre. It accepts most of its patients from other hospitals in the UK and overseas. The severity of injury, the presence of a tracheostomy, urinary catheter and pressure sores predisposes this group of patients to colonisation or infection with Methicillin resistant Staphylococcus aureus (MRSA). The NSIC uses simple but strict protocols for hygiene, screening for MRSA, and source isolation of known or suspected MRSA carriers in single room accommodation to control the spread of MRSA in the centre. A retrospective search of microbiology and patient records revealed that in 4 years there had been 24 admissions with MRSA, with a total of 1421 isolation days. There was only one outbreak of MRSA. This involved three patients. Hygiene, screening of potential MRSA carriers together with single room isolation can limit the spread of MRSA. PMID- 7885716 TI - A computer assisted follow up system for spinal cord injury patients. AB - The comprehensive care of patients with traumatic spinal cord injuries (SCI) necessitates, among other things, a structured, life-long follow up. The high consumption of medical care in chronic SCI patients, often a result of diseases affecting many different organ systems, soon causes the cumulated medical documentation to be extensive and therefore hard to survey. The possibilities for rational patient management, adequate quality assurance, and clinical research may improve considerably by computerisation of medical records. A computerised medical records system for SCI has recently been developed, using a semistructured medical record format for data input and a medical entity dictionary for facilitated data storage and retrieval. The principles for developing this computer-assisted follow up system are described. PMID- 7885717 TI - Pediatric seatbelt injuries: diagnosis and treatment of lumbar flexion distraction injuries. AB - Motor vehicle accidents are the major cause of flexion-distraction injuries of the thoracolumbar spine. In a retrospective review, we present the results of operative treatment for six pediatric patients who sustained such injuries while wearing seatbelts. There were three purely ligamentous injuries, two bony injuries (Chance fractures), and one combination injury. There were also concomitant neurological and intra-abdominal injuries. Of note is that two patients had either their spinal or abdominal injury missed on initial evaluation. All patients were treated surgically with open reduction and internal fixation. At average follow up of 2 years, all patients had a full range of motion with no back pain. Five had returned to their preinjury activity levels, while the sixth patient was paraplegic from his injury but was able to ambulate at home with crutches and knee-ankle-foot orthoses. We recommend operative reduction and two-level fusion of these injuries when (1) instability is apparent in either a purely ligamentous injury or an overtly unstable fracture-pattern, (2) significant kyphosis is present which cannot be reduced or maintained in a cast, or (3) there is associated neurological or intra-abdominal injury. PMID- 7885718 TI - Changes in choline acetyltransferase distribution in the cervical spinal cord after reversible cervical spinal cord injury. AB - Reversible spinal cord injury (SCI) at C6 level in rats, produced by the weight placed method, resulted in a severe motor functional deficit initially, followed by a gradual recovery. During the recovery, choline acetyltransferase (CAT) distribution in the cervical spinal cord was investigated at 2, 4, 7, 14 and 28 days after the injury by quantitative immunohistochemistry with a fluorescence microphotometry system. At C6 level, the fluorescence intensity of the ventrolateral anterior horn (VLAH), which reflected the concentration of CAT, decreased to approximately 50% of that of the sham-operated group at 2 days. It then recovered to 60% at 4 days after the injury, and remained unchanged thereafter. Fluorescence intensities in VLAH at C4-5 and C7-8 levels decreased to approximately 60-70% at 2 days after the injury, but it recovered and increased to 110-130% thereafter. PMID- 7885719 TI - Sexual adjustment after spinal cord injury-comparison of partner experiences in pre- and postinjury relationships. AB - This study compared the emotional and sexual aspects of relationships before and after spinal cord injury, from the partner's point of view. In addition, the personality characteristics of the partners were investigated. Twenty-six relationships were established before the injury and 23 after. The couples in preinjury relationships had been married or cohabiting for 3.5-51 years (median 24 years), while postinjury relationships ranged from 1 to 8 years (median 2 years). There were substantial differences in age between preinjury and postinjury partners, 21-79 years (median 51 years) and 18-45 years (median 28 years), respectively. Data collection included an 80-item questionnaire, designed to determine different aspects of sexuality, a visual analogue scale Quality of Life (VAS QL) measure and an established inventory of personality characteristics, the Karolinska Scales of Personality (KSP). Eighty-eight per cent of the partners in preinjury and 86% in postinjury relationships considered their overall relationship to be satisfactory. Concerning the sexual aspects of the relationships, several differences were revealed, all favouring postinjury relationships. Some of these held true even when age was treated as a significant factor and statistically controlled. Although the frequency of sexual activity and the variety of sexual expressions used were lower in the preinjury relationships, and perceived deterioration of sex life due to the injury was higher among preinjury partners, there was no significant difference between the two groups in satisfaction with current sex life. Thus, age seems to be a more important factor for sexual adjustment after a spinal cord injury, rather than whether the relationship is established before or after injury. The partners' personality characteristics differed only slightly from those of a sex and age matched reference group and not at all between partners in pre- and postinjury relationships. PMID- 7885720 TI - Psychosocial outcome following spinal cord injury. AB - Studies have indicated that loss of social contact remains the primary complaint of people with head injuries many years after discharge. In an attempt to disentangle specific and nonspecific effects of head injury a study was undertaken to compare a group of 15 men with severe closed head injuries and their wives, with a group of 15 men with complete, traumatic spinal cord injuries and their partners (n = 60). Time since discharge extended from 4 months to several years. This paper focuses primarily upon the results and implication of the responses from the group of men with spinal cord injuries and their partners. The Interview Schedule for Social Interaction was correlated with the Leeds Scale for the Self Assessment of Anxiety and Depression. All groups reported low availability and adequacy of social integration and exhibited high levels of depression. The group of men with spinal cord injuries had the lowest scores for the availability of social integration, indicating that the social isolation which has previously been identified amongst people with head injuries may not be attributable solely to brain damage. PMID- 7885721 TI - Reproducibility of Nordic Sleep Questionnaire in spinal cord injured. AB - A recently proposed Nordic Sleep Questionnaire (NSQ) comprises 26 questions concerning qualitative and quantitative aspects of the respondent's sleep habits. Its reproducibility was evaluated in 32 spinal cord injured individuals (SCI), 24 men and eight women (23-72 years), and 79 normal subjects, 23 men and 56 women (19-77 years). They completed the NSQ twice at a median interval of 15 days (range 10-26) and 27 days (range 4-103) respectively. The group of normal subjects were evenly divided into group 26, i.e. those who completed the two NSQs within 26 days, and group 27 with 27 days or more between their replies. Generally, group 27 showed no worse test-retest agreement than group 26. In addition, the respondents' answers, with a few exceptions, were reasonably stable in terms of test-retest agreement or standard deviation. The SCI group exhibited the same level of reproducibility, although they had more 'pathology' to report and thus more scope for contradicting themselves. The questions in the NSQ generally were satisfactorily reproducible. However, answers to the ordered five point questions about sleepiness in the morning and during the daytime ought to be interpreted with caution. The same may be said about the number of minutes required to fall asleep, and the duration of daytime naps. PMID- 7885722 TI - Reflex sympathetic dystrophy. PMID- 7885723 TI - On recycling in the operating room. PMID- 7885724 TI - Scoliosis in Rett syndrome. AB - Scoliosis is the most common orthopaedic problem encountered in Rett syndrome. It is characterized by a long C-shaped thoracolumbar curve of neurologic origin. The occurrence of scoliosis in Rett syndrome is age-dependent, with a reported incidence of 36% to 100%. The onset of scoliosis is usually before age 8 years, and rapid curve progression is usually detected early in the second decade. In Rett syndrome, sagittal deformity with excessive kyphosis can progress and necessitates close observation. Orthotic treatment does not alter the natural history of scoliosis or kyphosis. Indications for surgery are curve progression exceeding a 40 degree or 45 degree Cobb angle or curves that cause pain or loss of function. Anterior discectomy, interbody fusion, and posterior fusion with instrumentation can achieve improved correction in young adolescents with significant curves. Surgical intervention should include fusing the scoliotic and the excessively kyphotic segments. PMID- 7885725 TI - Comparison of axial T1 spin-echo and T1 fat-saturation magnetic resonance imaging techniques in the diagnosis of chondromalacia patellae. AB - To test the diagnostic value of T1 spin-echo and T1 fat-saturated magnetic resonance images (MRIs), we reviewed axial T1-weighted images with and without fat saturation in 20 patients with clinically suspected chondromalacia of the patella. All scans were obtained on 1.5-MR units. The scans were randomly ordered and reviewed independently at different times by two radiologists without knowledge of the arthroscopy results. The sensitivity of the individual techniques for detecting grade 3 or 4 chondromalacia patellae was 92% for fat saturated axial T1-weighted images alone, and 67% for axial T1-weighted images without fat saturation. The sensitivity of the combined techniques was 100% for grades 3 and 4 and 90% for all grades (0 to 4). Chondromalacia patellae is diagnosed more accurately by using T1 fat saturation than by using T1 spin-echo images. With a combination of the two techniques, accuracy is 90% to 100%. PMID- 7885727 TI - A 37-year-old man with left foot pain. Symptomatic accessory navicular synchondrosis. AB - The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon. The initial history, physical findings, and roentgenographic examinations are found on this page. The clinical and roentgenographic diagnoses are presented on the following pages. PMID- 7885726 TI - The use of somatosensory evoked potentials to prevent ischemic neural damage during preoperative embolization of a vascular renal metastasis. AB - Tumors at the spinal cord level present challenging surgical problems. Hypernephromas and other tumors may have copious bleeding at the time of resection. This bleeding can be reduced by preoperative embolization resulting in a dramatic decrease in surgical morbidity. However, embolization does carry a risk of spinal cord infarction and resultant neurologic injury. To monitor this, somatosensory evoked potentials (SSEPs) were evaluated during embolization, with a resultant termination of the procedure after significant SSEP changes and clinical symptoms indicated cord ischemia. The SSEP readings normalized 24 hours later, by the time of surgical resection. We present a relevant case history and review of the literature on this subject. Clearly, SSEPs, and in the future, motor evoked potentials (MEPs), serve as a valuable adjunct to monitoring spinal cord function during embolization and may prevent preoperative ischemic injury. PMID- 7885728 TI - Simple intraoperative traction system for acetabular fracture surgery. AB - The open reduction and internal fixation of complex acetabular fractures generally require some amount of sustained intraoperative traction. This traction can be provided by either specialized traction tables or scrubbed assistants. Both methods have their advantages and disadvantages. Specialized traction tables provide excellent controlled traction but are costly. Interested assistants are less costly, but at many institutions an adequate number of them are unavailable. We describe the design, construction, and use of a simple intraoperative traction device to aid in the open reduction and internal fixation of acetabular fractures. PMID- 7885729 TI - The regulation of malaria parasitaemia: parameter estimates for a population model. AB - Classical studies of non-immune individuals infected with Plasmodium falciparum reveal that the infection may be regulated for long periods at a relatively stable parasite density, despite the enormous growth potential of a parasite that continually replicates within host erythrocytes. This suggests that the parasite population may be controlled by density-dependent mechanisms, and in theory the most obvious of these is competition between parasites for host erythrocytes. Here we evaluate the role of this mechanism in the regulation of parasitaemia, by modelling the basic population interaction between parasites and erythrocytes in a form that allows all the essential parameters to be estimated from clinical data. Our results show that competition cannot account for the total regulation of P. falciparum, but when combined with immune mechanisms it may play a more important role than is generally supposed. Further analysis of the model indicates that in the long term, parasite replication at low parasite densities can contribute significantly to the high degree of anaemia observed in natural infection, a conclusion which is not obvious from simple clinical observation. PMID- 7885730 TI - Host-parasite relationship between congenital Toxoplasma infection and mouse brain: role of small vessels. AB - Small vessels showing inflammatory cell infiltrates were invariably observed in the vicinity of intact Toxoplasma tissue cysts within the brains of mice congenitally infected with the protozoan. Lymphocytes were observed in intimate contact with the luminal aspect of the endothelium, penetrating into the thickened basal lamina and in the perivascular area, which also contained macrophages and neutrophilic granulocytes. Rarely, lymphocytes were observed attached to the outer membrane of the host neurone which contained a Toxoplasma tissue cyst and within the inflammatory infiltrate associated with a disintegrating cyst. An hypothesis is presented which combines these morphological observations to explain the events associated with tissue cyst associated recrudescence of latent Toxoplasma infection in mouse brain. PMID- 7885731 TI - Differentiation between human and animal strains of Cryptosporidium parvum using isoenzyme typing. AB - Isoenzyme typing was used to study a number of oocyst isolates of Cryptosporidium parvum from different geographical locations and of human or animal origin. All isolates showed identical enzyme motility when glucose phosphate isomerase (GPI; 23 isolates tested) or lactate dehydrogenases (LDH; 20 isolates tested) was assayed. However, two isoenzyme forms were observed with phosphoglucomutase (PGM; 9 animal isolates showed one form, while 8/9 human isolates showed a second form) and hexokinase (HK; 4 human isolates showed one form and 6 animal isolates showed a second form). Thus, PGM and HK each exhibit 2 isoenzymes corresponding to 2 parasite populations associated with separate hosts. The data from this study, plus supportive evidence obtained by different methods and by independent researchers, lend support to the hypothesis that separate cycles of transmission of C. parvum may exist within human and animal hosts. PMID- 7885732 TI - Finding and recognition of the snail intermediate hosts by 3 species of echinostome cercariae. AB - Finding and recognition of snail second intermediate hosts was studied in cercariae of 3 echinostome species. The cercariae of the 3 species accumulated in snail-conditioned water (SCW) with 2 types of orientation mechanisms and responded to different small molecular weight ( < 500 Da) components of SCW. Pseudechinoparyphium echinatum and Echinostoma revolutum cercariae returned by swimming an arc, when swimming in decreasing concentration gradients of SCW (turn back swimming). The stimulating cues of SCW were identified as hydrophilic organic molecules, probably possessing amino groups. Amino acids contributed to the attractivity of SCW, at least in P. echinatum, but they could not account for the complete attractivity of SCW. Hypoderaeum conoideum were directed chemotactically and swam along increasing concentration gradients of small peptides within SCW, but in decreasing SCW gradients they showed no turn-back swimming. Chemotactic orientation in H. conoideum only started 1 h after emission, which may assist the cercariae to leave the immediate area of their first intermediate host snails and to disperse. Attachments occurred specifically to snail hosts in the 3 species and were stimulated by macromolecular mucus compounds, probably mainly by viscoelastic properties of the mucus. The results of this study show, that host-finding mechanisms and the stimulating host cues of snail invading echinostome cercariae differ considerably from those of schistosome miracidia. PMID- 7885733 TI - Immunocytochemical demonstration of a SALMFamide-like neuropeptide in the nervous system of adult and larval stages of the human blood fluke, Schistosoma mansoni. AB - The localization and distribution of SALMFamide immunoreactivity (IR), SI(GFNSALMFamide), in the nervous system of both the adult and larval stages of the trematode Schistosoma mansoni has been determined by an indirect immunofluorescent technique in conjunction with confocal scanning laser microscopy (CSLM). Immunostaining was widespread in the nervous system of adult male and female S. mansoni. In the central nervous system (CNS), IR was evident in nerve cells and fibres in the anterior ganglia, cerebral commissure and dorsal and ventral nerve cords. In the peripheral nervous system (PNS), IR was apparent in nerve plexuses associated with the subtegmental musculature, oral and ventral suckers, the lining of the gynaecophoric canal, and in fine nerve fibres innervating the dorsal tubercles of the male worm. In the reproductive system of male and female worms, S1-IR was only observed around the ootype/Mehlis' gland complex in the female. Immunostaining was also evident in the nervous system of both miracidium and cercarial larval stages. A post-embedding, IgG-conjugated colloidal gold immunostaining technique was employed to examine the subcellular distribution of SALMFamide-IR in the CNS of S. mansoni. Gold labelling of peptide was localized over dense-cored vesicles within nerve cell bodies and fibres constituting the neuropile of the anterior ganglia, cerebral commissure and nerve cords of the CNS. Antigen pre-absorption studies indicated that the results obtained do suggest S1-like immunostaining and not cross-reactivity with other peptides, in particular FMRFamide. PMID- 7885734 TI - F-10 nuclear binding proteins of Schistosoma mansoni: structural and functional features. AB - By incubating total protein extracts of Schistosoma mansoni with 3H-17-beta estradiol and 20-hydroxyecdysone, steroid binding proteins were detected in both male and female worms. The interaction of nuclear proteins with a restriction fragment of the gender and stage-specific gene F-10 was investigated using the 'band-shift' technique. Male and female nuclear proteins bound in a distinct way to the fragment of this gene containing putative regulatory consensus motifs. Among the nuclear proteins, only those rich in cysteine residues bound to DNA. In vitro incubation of live worms with the oestrogen antagonist Tamoxifen, altered the pattern of the DNA binding proteins, producing in females a profile similar to that obtained with male worm protein extracts. This effect of Tamoxifen could not be correlated to inhibition of protein biosynthesis. These results suggest that the regulation of transcription of the F-10 gene might involve steroid receptors. PMID- 7885735 TI - Detection of host DNA sequences including the H-2 locus of the major histocompatibility complex in schistosomes. AB - The mouse type 2 Alu (B2) sequence was detected in both DNAs of Schistosoma mansoni and S.japonicum except for the cercarial stage by the polymerase chain reaction (PCR). Using several kinds of mouse STMS (sequence tagged microsatellite site) primer sets, PCR products related to the host were found in the DNAs of S. mansoni as well as of S.japonicum. Products could be detected only in the DNA of S. japonicum using certain STMS primer sets. The fact that no products could be amplified from the DNAs of both parasites when other kinds of STMS primer sets were used suggests unequal incorporation of the host DNA into the schistosomes. Furthermore, the sequence of the N-terminal domain of H-2, the mouse major histocompatibility complex (MHC), was detected in the DNAs from S. mansoni miracidium, male adult and S. japonicum adults, whereas the sequence of the C2 domain of H-2 was found only in the DNAs of S. japonicum adults. This evidence that host DNA sequences, including the class I MHC, exist heterogeneously in the DNAs of schistosomes might provide an important insight for further understanding of host-parasite immune interactions. PMID- 7885736 TI - Detection of linkage disequilibrium in Trypanosoma brucei isolated from tsetse flies and characterized by RAPD analysis and isoenzymes. AB - This study analyses the different populations of Trypanosoma brucei spp. which may coexist within the midgut of wild tsetse flies (Stevens et al. 1994). Cloned trypanosome populations characterized by multilocus enzyme electrophoresis (MLEE) were further analysed by the random amplified polymorphic DNA (RAPD) technique, allowing detection of genetic variation at a finer level than that possible by MLEE. Genetic distance matrices derived from the results of each of the two biochemical methods were calculated and compared using a computer program based on the method of Mantel (1967). The observed correlation was used to investigate the degree of linkage disequilibrium (LD) in the data, association between unrelated polymorphic markers providing a measure of the departure from panmixia. The potential of each biochemical method to detect linkage was evaluated by an extended Mantel test. The MLEE/RAPD correlation test evidenced significant LD within the population, suggesting a predominantly clonal method of reproduction for these West African trypanosomes. Analysis of RAPD data by the extended Mantel test also showed significant LD, while the results with MLEE data were less conclusive, providing an indication of the relative potential of the two techniques to detect fine genetic variation. PMID- 7885737 TI - Role of small mammals in the epidemiology of toxocariasis. AB - Studies were conducted on the role of small mammals in maintaining toxocariasis foci in urban, rural and montane biotopes. The lowest relative density of small mammals was recorded in the urban locality and the highest in the rural and montane localities. Anti-Toxocara antibodies were most frequently detected in synanthropic and hemisynanthropic species Mus musculus, Apodemus agrarius and Micromys minutus--32.0, 30.4 and 25.0%, respectively. The highest seropositivity was found in small mammals from the urban and rural localities--22.2 and 21.6%, respectively. Toxocara canis was most prevalent in urban stray dogs (75.0%) and least prevalent in foxes from the montane locality (7.0%). The prevalence of Toxocara cati in cats at the urban, rural and montane localities was 66.2, 65.2 and 76.9%, respectively. In clinically healthy human populations, the highest seroprevalence was detected in the rural locality (14.0%). Children of the same area were 3 times more seropositive (12.9%) than those from the urban and montane localities (4.3 and 4.0%). Our studies suggest an important role for small mammals as paratenic hosts--reservoirs of Toxocara larvae--in maintaining toxocariasis foci. In this respect toxocariasis may be classified as an anthropopurgic focal zoonosis. PMID- 7885738 TI - Comparative effects of mites and lice on the reproductive success of rock doves (Columba livia). AB - We report experimental data comparing the effects of Mesostigmatid mites and Ischnoceran lice on the reproductive performance of a single group of captive rock doves (Columba livia). Several components of host reproductive success were compared for the two groups, including number of eggs laid, hatching success, nestling growth rates, fledging success, post-fledging body mass and survival. Adult body mass and survival were also compared. There was a dramatic difference in the effects of the mites and lice. The former drove host reproductive success to zero, mainly by agitating adults and causing them to incubate eggs less faithfully. Nestling growth rates and post-fledging survival were also significantly reduced by mites. Lice showed no effect on reproductive success whatsoever, even though the feather damage they cause is known to have energetic consequences (Booth, Clayton & Block, 1993). Neither parasite had a significant effect on adult birds. Although Ischnocera are found on most species of birds, our results for lice constitute the first experimental test of the impact of Ischnocera on avian reproductive success (preliminary report by Clayton & Tompkins, 1994). We discuss reasons for the different effects of mites and lice, including the relationship of horizontal (mites) and vertical (lice) transmission to the evolution of virulence. PMID- 7885739 TI - Ascaris infections in humans from North America: molecular evidence for cross infection. AB - Cases of human Ascaris infection occur sporadically in areas such as N. America and Western Europe, where this parasite is thought to be non-endemic. Clinical case histories suggest that many of these cases may be cross-infections from pigs. I describe patterns of variation in the ribosomal DNA of Ascaris from 9 such cases. For comparative purposes, I also describe patterns of variation in parasites obtained from pigs and humans from worldwide locations. A Hae III restriction site distinguishes two classes of rDNA repeats; repeats bearing this restriction site were found in > 96% of parasites from pig populations worldwide and in all 9 worms from humans in N. America. In contrast, repeats bearing this restriction site were detected in < 2% of parasites from humans in endemic areas. The molecular data clearly incriminate pigs as the source of infection in the N. American cases. I discuss evolutionary and public health implications of incomplete host fidelity in Ascaris. PMID- 7885740 TI - Mitochondrial DNA and Ascaris microepidemiology: the composition of parasite populations from individual hosts, families and villages. AB - Patterns of genetic subdivision in parasite populations can provide important insights into transmission processes and complement information obtained using traditional epidemiological techniques. We describe mitochondrial sequence variation in 265 Ascaris collected from 62 individual hosts (humans and pigs) from 35 households in 3 Guatemalan locations. Restriction mapping of individual worms revealed 42 distinct mitochondrial genotypes. We ask whether the mitochondrial genotypes found in worms from individual hosts, from families of hosts and from villages represent random samples from the total Ascaris population. Patterns of genetic subdivision were quantified using F-statistics, while deviations from the null hypothesis of randomness were evaluated by a simple resampling procedure. The analysis revealed significant deviations from panmixia. Parasite populations were strongly structured at the level of the individual host in both humans and pigs: parasites bearing the same mitochondrial genotype were found more frequently than would be expected by chance within hosts. Significant heterogeneity was also observed among populations from different villages, but not from different families within a village. The clustering of related parasites within hosts suggests a similar clustering of related infective stages in the environment and may explain why sex ratios in Ascaris are female-biased. We discuss aspects of Ascaris biology which may lead to the observed patterns. PMID- 7885741 TI - Partial characterization of the carbohydrates of the eggs (oncospheres) of the tapeworm, Hymenolepis diminuta. AB - The carbohydrate constituents of whole eggs and fractions derived from the eggs of Hymenolepis diminuta were partly characterized. Whole eggs contained 9.6 ng of carbohydrate (phenol-sulphuric acid-positive material) per egg, and 3.6 ng of glucose. Analysis of hydrolysed eggs by HPLC demonstrated the presence of glucose, galactose, glycerol, N-acetylgalactosamine, and 2-deoxyribose. Isolated egg shells and the KOH-stable, ethanol-precipitable fraction (putative glycogen) of eggs contained 26 and 76%, respectively, of the total carbohydrate associated with eggs. Glucose and galactose were present in both of these samples, but only glucose was present in the KOH-stable, ethanol-precipitable fraction isolated from chemically deshelled eggs; thus, the source of the galactose in the KOH stable, ethanol-precipitable fraction isolated from whole eggs was the egg shells. These data confirm earlier reports that the shells contain carbohydrate; the data demonstrate further that only two monosaccharides (glucose and galactose) are present in the shells, and that they are present as high molecular weight polymers. The ethanol-soluble fraction of eggs contained 2.5% of the total carbohydrate in eggs, and glucose accounted for < 1% of the ethanol-soluble carbohydrate. Analysis of the ethanol-soluble fraction by HPLC demonstrated that the predominant monosaccharides were glycerol and mannose, with smaller quantities of 2-deoxyribose and 2-deoxyglucose. The absence of a 'free pool' of glucose in eggs, and the presence of large amounts of glycerol and mannose, suggest that the pathways of intermediary carbohydrate metabolism in eggs might be very different from those in adult tapeworms. PMID- 7885742 TI - The managed care mystery thriller: fact, fiction or both? PMID- 7885743 TI - An innovative method of administering i.v. medications to children. AB - Intravenous medications, especially antibiotics, should be infused in a timely fashion, with minimal irritation to the vessel, with the least chance of infiltration, and without causing fluid overload. Nurses at one institution were concerned that the method they were using was not fulfilling these desired outcomes. Medications were not consistently being administered within the appropriate time frame (usually 30 to 60 minutes) and the possibility of fluid overload existed. Time that nurses spent administering and checking on the medication was excessive. After reviewing alternative methods, nurses implemented a method that uses syringe tubing. Advantages, disadvantages, and a guideline for use are described. PMID- 7885744 TI - Peripheral intravenous lock irrigation in children: current practice. AB - Current practice for irrigation of peripheral intravenous (IV) locks in children was determined from responses to a questionnaire sent to selected children's hospitals nationwide. Although considerable variation in practice exists, the most common practice is to irrigate peripheral IV locks with 1 milliliter (ml) of a solution containing 10 units of heparin per ml of normal saline every 8 hours. These results are based on a response rate of 74.4% (N = 32). PMID- 7885745 TI - An IV therapy teaching tool for children. AB - IV therapy is an anxiety provoking procedure for children who are hospitalized and their families. Adequate preparation can ease children's fears and promote cooperation. A teaching tool was designed to be used with medical play to prepare preschoolers and school-age children for the procedure. An understanding of the use of learning principles to guide design can assist nurses in developing similar teaching tools for children. PMID- 7885746 TI - Developing a pediatric patient-family education program. AB - Pediatric patient and family education is an important component of pediatric health care delivery. Planning and implementing a pediatric patient-family education program includes producing professional materials that are patient and family focused. Nurses should develop educational information that is appropriate to give to parents and children and adapt this information to the needs of their institutions. PMID- 7885747 TI - Children describe life after Hurricane Andrew. AB - Hurricane Andrew, which devastated the south Florida coast in August 1992, left over 250,000 people homeless with multiple health and social problems. This nursing study explored the experiences of 17 children, ages 5 through 12, who lived in the geographic area of storm damage. Common experiences described by the children included remembering the storm, dealing with after-effects, and reestablishing a new life. In general, children described a sense of strangeness, articulated as "life is weird" after the hurricane. In addition to stressful responses, many positive reactions were described by children in the study, revealing that the disaster also had a maturing effect. PMID- 7885748 TI - Pediatric lupus and the role of sun protection. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs of the body. The skin is commonly targeted by the inflammatory process of SLE, and exposure to sunlight is known to be a potential cause of dermatologic as well as systemic manifestations of SLE. Sun protection is a critical part of treating the disease and preventing sequelae. While other manifestations of the disease are important, discussion will be limited to ultraviolet light (UVL) and the resulting abnormal response to light exposure that may occur in lupus. Education about the importance of sun protection is an integral part of the treatment of children with lupus. PMID- 7885749 TI - The guidelines for immunizations have changed ... again! AB - Once again, the Advisory Committee on Immunization Practices (ACIP) and the Centers for Disease Control (1994) issued new guidelines for immunizations. Pediatric nurses should be aware of these new recommendations, summarized in this article. PMID- 7885750 TI - Impact on the family of children who are technology dependent and cared for in the home. AB - PURPOSE: To compare the impact on family of four categories of technology dependent children. METHOD: A purposive sample of families receiving both public and private services in 13 cities representing census regions included 848 primary caregivers of technology-dependent children ages 3 months to 19 years being cared for at home. A structured telephone interview was used. FINDINGS: A significant difference among the four types of technology dependency for impact on the family was found (MANOVA F test = 9.43; p = 0.0001). One-way ANOVA F tests showed that the means among the four groups varied on the subscale: financial burden, family social impact, and personal strains. CONCLUSION: The findings have implications for nurses who provide support and assistance to families with technology-dependent children. PMID- 7885751 TI - Agency for Health Care Policy and Research releases new guidelines on HIV. PMID- 7885752 TI - Changing nurses' attitudes toward parenting in the NICU. AB - Developing insight into NICU nurses' attitudes toward active parenting and identifying issues regarding the provision of care to these infants are essential if changes in clinical practice are to occur. Role negotiation and active advocacy provide direction for developing successful nursing interventions. PMID- 7885753 TI - Nedocromil sodium (Tilade). AB - Nedocromil sodium is a well-tolerated antiasthmatic agent for initial therapy in patients with mild or moderate asthma not well controlled with inhaled beta-2 agonists and/or where methylxanthines are indicated. Like cromolyn sodium, nedocromil sodium offers a potential alternative to inhaled corticosteroids as maintenance therapy in patients with mild or moderate asthma not adequately controlled by bronchodilators. Furthermore, cromolyn sodium and nedocromil sodium may also reduce the usage of corticosteroids and provide some additional symptom control in patients whose asthma is not suitably controlled by optimal doses of inhaled corticosteroids. Both nedocromil sodium and cromolyn sodium are more efficacious than placebo for controlling of asthma, however, few studies have compared the effectiveness of cromolyn versus nedocromil at this time. Further experience and comparison studies of nedocromil sodium with cromolyn sodium in children are required before the role of nedocromil sodium as maintenance treatment in young asthmatic patients can be defined. PMID- 7885755 TI - Setting home care standards. AB - Setting standards for home health care is a necessary component to ensuring the delivery of quality care efficiently and effectively. The generic standards established by the American Nurses' Association are reviewed while other resources available when pursuing the development of home health standards are described. The author discusses the concept of developing standards based on cost, quality, and process. PMID- 7885754 TI - Nursing weakened by federal education program consolidation. PMID- 7885756 TI - What is your assessment? Anaphylactic reactions to bee stings. PMID- 7885757 TI - Lyme disease in children. AB - Lyme disease is becoming prevalent throughout the nation. This article will describe the etiology of Lyme disease, discuss ways of preventing the disease, and present methods for diagnosing and treating the disease. PMID- 7885758 TI - Another advantage of EMLA cream. PMID- 7885759 TI - Family: is there anything more diverse? AB - Families are small social systems that provide for nurturance, security and love, as well as the basics of existence. Families teach children how to be in the world. Families do not fit a single definition: diversity and variability characterize these systems held together primarily by commitment of family members to each other over time. Changes throughout the life stages and as a result of societal trends influence family structures and parenting styles. An expanded view of families and how they live is part of a family-centered model of care. A focus on family strengths is key to meaningful care. PMID- 7885760 TI - Ethics lessons in a teenager's story. PMID- 7885761 TI - Revamping British nurse education with Project 2000: focus on children's nursing. AB - The preregistration nurse education system in the United Kingdom is currently undergoing dramatic changes to meet the changing times and health care needs. Project 2000 has been an ongoing reality for nurses in the U.K. and demonstrates nursing's responsiveness to change and nurses' commitment to the public's health. PMID- 7885762 TI - A comparative study of health care for children with cancer in 1981 and 1991 in Taiwan. AB - This study compared the differences in health care for children with cancer in 1981 and 1991 in Taiwan. The concept of a well-established health care delivery system, including accessibility, continuity, efficiency, dynamism, and integration, served as the conceptual framework for the study. The results showed that: (a) medical care improved--the length of time between symptom and diagnosis was shorter, the number of clinic visits before diagnosis decreased, and the length of time for hospitalization was much shorter with most children receiving their health care in the hospital near their home town; (b) pain control at the terminal stage improved with 70% of mothers stating that their child's pain had received appropriate care; and (c) the role and function of the physician and the nurse were more recognized by parents. The results of the study will assist program planners who are helping children with cancer to improve their health care system. PMID- 7885763 TI - Caring for children during procedures: a review of the literature. AB - Nurses are being bombarded with recommended interventions to help children and their parents manage procedures. In order to select effective and appropriate interventions, nurses should carefully review the literature related to these recommendations. In turn, nurses must also document their care of children during procedures so that interventions selected can be examined, validated, and reinforced. PMID- 7885764 TI - Families with medically fragile children: an exploratory study. AB - Because of increased survival rates for children with critical illnesses and injuries coupled with early discharge programs, medically fragile children are increasingly likely to receive care in the home. The purpose of this exploratory study was to provide an initial description of the typical decisions and problems families experienced on a day-to-day basis, family coping strategies (F-COPES), and family resources (Family Strengths Scale). A convenience sample of 10 families, recruited from a pediatric rehabilitation hospital, participated in a one-hour, in-home interview. Respondents included the child's mother (n = 4), mother and father (n = 2), grandmother (n = 2), grand aunt and uncle (n = 1), and legal guardian (n = 1). Family members were likely to consult health care professionals for treatment-related issues but not for child care issues such as toileting. Coping strategies used most often included Mobilizing Family and Acquiring Social Support. Comments indicated a need for additional financial resources and alternative child care services. PMID- 7885765 TI - Sleepless nights: obstructive sleep apnea in the pediatric patient. AB - Obstructive sleep apnea syndrome (OSAS) is a subtle but severe sleep disorder of early childhood. It occurs in 1.6%-3.4% of children between 6 months and 6 years of age. OSAS is often difficult to detect, and may have long-term consequences, including failure to thrive, behavioral disturbances, developmental delay, and cor pulmonale. Pediatric nurses are pivotal in assessing the clinical symptoms of OSAS so that prompt evaluation and treatment can be initiated. Early symptoms of OSAS include awakening with a startle or gasp, restlessness, retractions, inspiratory stridor, mouth breathing, and excessive sweating. Treatments vary, and include adenotonsilectomy, nasal continuous positive airway pressure (NCPAP), behavior modification, and tracheostomy. PMID- 7885766 TI - Comfort and consolation: a nursing perspective on parental bereavement. AB - The death of a child is the most potentially devastating event that a family can ever experience (Lundin, 1984). The death of a child also has a significant impact on the lives of health care professionals who must provide care both for the child and for the grieving family members. Nurses can assume a critical role in supporting bereaved families by becoming cognizant of parental grief responses and by developing an awareness of the needs of families in planning appropriate interventions. PMID- 7885767 TI - What's your assessment? Tinea corporis. PMID- 7885768 TI - Using NCAST and the HOME with a minority population: the Alaska Eskimos. AB - PURPOSE: To test applicability of the NCAST and HOME assessment tools in the Eskimo population. METHOD: A cross-sectional descriptive study of Alaskan native families from two villages used the NCAST and HOME child assessment tools. Comparisons using t-test were made to normative data. ANCOVA was used to test effects of demographic differences. RESULTS: Several significant differences were found on subscales of the NCAFS, NCATS, and HOME, although the total scores of the NCAFS and the NCATS were not significantly different. Caregiver education and ethnicity were significant covariates. CONCLUSIONS: NCAFS and NCATS appears to have sufficient breadth to allow for cultural differences. The HOME scale items measure some aspects of the environment that appear to be culture specific. PMID- 7885769 TI - Acetaminophen's potential for morbidity and mortality. PMID- 7885770 TI - Selected outcomes of technology dependent children receiving home care and prescribed child care services. AB - Traditionally, parents of technology dependent children have had two child care choices: prolonged hospitalization or home care. Prescribed child care centers have emerged to provide parents another care alternative. Prescribed child care parents reported fewer communicable diseases for children, and a coping level equal to or better than home care parents as well as lower monthly nursing costs. PMID- 7885771 TI - GAO releases preliminary findings on school-based health centers. PMID- 7885772 TI - The cardiovascular health profile: implications for health promotion and disease prevention. PMID- 7885773 TI - Commentary: guidelines on forgoing life-sustaining medical treatment. PMID- 7885774 TI - Henri Landwirth is recipient of Pediatric Nursing's Humanitarian Award. PMID- 7885775 TI - The United Nations' International Year of the Family. PMID- 7885776 TI - Abdominal tuberculosis in children. AB - Four boys with abdominal tuberculosis, one of whom had acquired immunodeficiency syndrome, are presented. Abdominal imaging findings on plain radiography, ultrasonography, computed tomography, and gastrointestinal contrast studies included tuberculous peritonitis and ascites in all patients, tuberculous adenopathy in two, gastrointestinal tuberculosis in two, and omental tuberculosis in two. The radiographic features particularly characteristic of abdominal tuberculosis were: (1) low attenuating adenopathy with rim enhancement, (2) omental or ileocecal inflammatory mass, (3) high density ascites, and (4) gastrointestinal enteritis involving the ileocecal region. All patients had acid fast bacilli identified in cultures of bodily fluids and/or pathologic specimens and three patients had cultures positive for Mycobacterium tuberculosis. The patient with a negative culture had a positive PPD skin test and a surgical specimen showing caseating granulomata and acid-fast bacilli in the omentum. The radiologist must maintain a high degree of suspicion for abdominal tuberculosis particularly in normal or immunosuppressed children with acquired immunodeficiency syndrome. Fine needle aspiration and biopsy of abdominal adenopathy, inflammatory mass or ascites may be necessary for diagnosis. PMID- 7885777 TI - Value of the lateral chest radiograph in tuberculosis in children. AB - The value of the lateral chest radiograph, often considered a useful adjunct in the detection of hilar adenopathy, was evaluated in a prospective study of 449 children assessed for tuberculosis. Of these children 298 presented to the hospital with signs and symptoms suggestive of tuberculosis, while 151 were investigated in a regional clinic solely because they were in close contact with an adult household member on treatment for tuberculosis. Tuberculosis was confirmed by culture in 176 of the 449 children (39%). In 40 of these (23%) hilar adenopathy was visible on frontal and lateral view, in 19 of the 176 confirmed cases (11%) only on a frontal view and in 22 (13%) on a lateral view only. Probable tuberculosis was diagnosed in a further 140 of the 449 children (31%), and hilar adenopathy was visible on frontal and lateral views in 39 of these children (28%), on the frontal view only in 8 (6%) and on the lateral view only in 27 (19%). In the symptomatic children investigated in the hospital, and the asymptomatic children investigated in the clinic, hilar adenopathy was detected on the lateral chest radiograph only in 36 (12%) and 14 (9%) cases respectively. Lateral chest radiographs will considerably improve the accuracy of the diagnosis of childhood tuberculosis. PMID- 7885778 TI - The ultrasonic evaluation of psoas abscess (tropical pyomyositis) in children. AB - Psoas abscesses in children are not rare in tropical and sub-tropical countries and are related to staphylococcus aureus infection and poor socio-economic conditions. The condition should be considered in all children with the triad of pyrexia, flank pain and hip symptoms. Ultrasound is a readily available and definitive examination. Sonography was used in a series of 45 patients. The findings are discussed and two representative cases presented. PMID- 7885779 TI - Ultrasonic signs of pelvic osteomyelitis in children. AB - The ultrasonic findings were reviewed in 13 children in whom pelvic osteomyelitis was diagnosed by a positive 99mtechnetium methylene diphosphonate (MDP) bone scan in conjunction with clinical and laboratory features of osteomyelitis. All patients presented with pain in the region of the hip joint. In six patients the ultrasound study was confined to the hip joint, and all six had normal findings. In seven patients the ultrasound study was extended to include the pelvis. Deep soft tissue swelling was demonstrated in six of these, including a periosseous abscess in one case. Ultrasonography was negative in one patient with a 5-week history, whose pelvic osteomyelitis was resolving at the time of the ultrasound study. Oedema of the obturator internus and externus muscles was observed in osteomyelitis affecting the pubis and ischium, and of the iliacus and/or the gluteus medius muscle in osteomyelitis of the ilium. In children presenting with hip pain who have a normal hip ultrasound study, extension of the ultrasound examination to include these four pelvic muscles may help to identify and document the progression of acute pelvic osteomyelitis. PMID- 7885780 TI - MR signal characteristics of cadaveric bone allografts in three children with primary bone tumors treated with limb salvage therapy. AB - Three children with adult cadaveric bone allografts for the treatment of bone malignancies are presented. Follow-up magnetic resonance (MR) imaging demonstrated decreased signal on T1-weighted imaging and increased signal on T2 weighted imaging in the allograft without clinical evidence of recurrent disease. These signal characteristics appear to be a normal finding in cadaveric bone allografts and should not be mistaken for recurrence. The finding may reflect persistent marrow necrosis within the allograft marrow cavity. PMID- 7885781 TI - Chest radiographic features of thoracic metastatic disease in adolescents with colon cancer. AB - This study describes chest radiographic features of thoracic metastatic disease (TMD) in patients referred for colon cancer to a pediatric oncology hospital. The study group was comprised of 9 patients (7 males, 2 females, age 13-19 years) with serial chest radiographs demonstrating TMD from colon cancer. All patients had a chest radiograph performed within the 2 months prior to death. The median interval from diagnosis of colon cancer to appearance of radiographic TMD was 3 months. Four of nine patients had TMD at presentation, eight of nine patients within 2 years of diagnosis. All abnormalities progressed on serial radiographs. The median interval from appearance of radiographic abnormalities to death was 2 months. Radiographic findings included pleural effusions (n = 6), lymphadenopathy (n = 5), lymphangitic carcinomatosis (n = 4), solitary pulmonary nodule (n = 2), and lobar atelectasis (n = 1). Five patients with pleural effusions initially had right-sided effusions. Radiographic TMD in adolescents with colon cancer usually occurs within 2 years of diagnosis. Once TMD manifests, the prognosis is dismal. Findings include pleural effusions, lymphadenopathy, lymphangitic carcinomatosis, solitary pulmonary nodules, and lobar atelectasis. We suggest that metastatic colon carcinoma should be included in the differential diagnosis for lymphangitic spread of tumor in adolescents. PMID- 7885782 TI - Acute monoblastic leukemia presenting with pericardial effusion and cardiac tamponade. AB - A previously healthy young child presented with a large pericardial effusion and cardiac tamponade. The chest radiography was key to the recognition of the pericardial effusion. Cytologic examination of the pericardial fluid ultimately established the diagnosis of acute monoblastic leukemia in the absence of associated clinical or laboratory findings. The pericardial fluid was vital for leukemic cell classification because the bone marrow has hypocellular and non diagnostic. This presentation of acute monoblastic leukemia is very rare, and in the three previously reported pediatric cases has been associated either with peripheral blasts or a history of preleukemia. When the cardiac configuration suggests pericardial effusion in a previously healthy young child, the diagnosis of new onset leukemia should be considered. PMID- 7885783 TI - Gastric adenocarcinoma metastatic to the testes in Peutz-Jeghers syndrome. AB - Peutz-Jeghers syndrome is associated with an increased frequency of gastrointestinal and extraintestinal malignancies. Ultrasound, CT, and MRI findings of testicular metastases from gastric adenocarcinoma in a boy with Peutz Jeghers syndrome are presented. PMID- 7885784 TI - Gastrointestinal smooth muscle tumors in children: report of three cases. AB - We report three rare smooth muscle tumors of the gastrointestinal tract (GIT) occurring in infancy. Two were benign leiomyomata and the other a leiomyosarcoma. The imaging features and presentation of leiomyosarcoma in childhood have not been previously described. PMID- 7885785 TI - Undifferentiated embryonal sarcoma of the liver: US and CT findings. AB - Six cases of undifferentiated embryonal sarcoma (UES) were reviewed to determine their characteristic features on ultrasonography (US) (n = 5) and computed tomography (CT) (n = 6). US demonstrated a single large, echogenic mass with some anechoic spaces. Contrast-enhanced CT scan revealed a well-demarcated low attenuation mass with hyperdense septations of variable shape and thickness. Discrepancy of internal architecture on US and CT was one of the important characteristics of UES. CT numbers were 25-47 HU in low-attenuation areas. Enhancing peripheral rim was found in four cases and some solid portions at the periphery or adjacent to the septa were found in all cases. Two patients who had follow-up US and CT without treatment showed enhancing solid portions, changing to hypodense as the tumor grew. When compared with the pathologic findings, US showed a more accurate representation of internal architecture than did CT. Familiarity with these US and CT findings of UES of the liver will be helpful in the differential diagnosis of primary hepatic tumors in childhood. PMID- 7885786 TI - Infradiaphragmatic bronchogenic cyst with high CT numbers in a boy with primitive neuroectodermal tumor. AB - Abdominal bronchogenic cysts are very rare with less than 20 published cases. We report the case of a retroperitoneal bronchogenic cyst in a 12-year-old boy, who initially presented with a primitive neuroectodermal tumor of the pelvis. Computed tomography (CT) showed a small, hyperdense nonenhancing mass adjacent to the right crus of the diaphragm. Follow-up CT after chemotherapy showed a decrease in CT attenuation of this mass, but a slight increase in size. At surgery the mass was loosely attached to the diaphragm and final pathology confirmed the diagnosis of a bronchogenic cyst. PMID- 7885788 TI - Serial renal sonographic evaluation of patients with Lesch-Nyhan syndrome. AB - The objective of this study was to review sequential renal sonograms of patients with Lesch-Nyhan syndrome obtained over several years to determine different sonographic patterns, the alterations in the patterns occurring over time and the relationship to management. Additional objectives were to evaluate the size of the kidneys, and to correlate the metabolic constituents of calculi with the therapeutic regimens and with the renal sonographic patterns. Serial sonograms of six patients with Lesch-Nyhan syndrome were reviewed for periods varying between 2 and 7 years with a mean of 4 years. The ages of the patients at the conclusion of the study were between 10 and 22 years. Three patterns of abnormal echogenicity were found; a punctate increase in echogenicity in the renal medullary pyramids, a diffuse increase in medullary pyramid echogenicity, and a pattern of increased echogenicity in the collecting system. These patterns were progressive but did not alternate on sequential scans, regardless of increasing or constant therapy. Analysis of calculi suggested patients were precipitating various metabolites concurrently; the incidence of metabolites appeared to be unrelated to therapy. Those patients with shadowing opacities, whether in the renal medulla or collecting system, were more likely to develop renal colic. Renal dimensions were small with renal function remaining normal. PMID- 7885787 TI - Idiopathic infantile arterial calcification: a surviving patient with renal artery stenosis. AB - Idiopathic infantile arterial calcification (IIAC) is a rare hereditary, fatal disease. Death occurs usually within the first 28 months of life. IIAC is characterized by calcifications along the internal elastic membrane and proliferation of the intimal layer of muscular arteries. Specific therapy consists of administration of diphosphonates, but its effectiveness has been a matter of controversy. We report a case treated with diphosphonates which has had an unusual outcome. PMID- 7885789 TI - Urine interleukin-6 and interleukin-8 in children with acute pyelonephritis, in relation to DMSA scintigraphy in the acute phase and at 1-year follow-up. AB - The relationship between urine interleukin-6 (IL-6) and interleukin-8 (IL 8)/creatinine quotients and 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy, performed within 10 days of acute first-time pyelonephritis and after 1 year, was studied in 41 children. The urine IL-6 and IL-8/creatinine quotients were also related to the urine N-acetyl-beta-D-glucosaminidase (NAG) and albumin/creatinine quotients. Presence of DMSA uptake defects, reflecting local inflammation, in children in the acute phase of pyelonephritis, were associated with elevated urine IL-6/creatinine quotients (median 27 pg/mumol); in children without DMSA changes there was no increase in quotients (median non-detectable) (P < 0.05). Persistent DMSA changes at the 1-year follow-up, probably reflecting renal scarring, were only seen in children with increased urine IL-6/creatinine quotients in the acute phase (P < 0.01). No correlation was found between urine IL-8 and DMSA uptake defects. Vesicoureteral reflux (VUR) at 6-8 weeks did not correlate with the urine cytokine levels in the acute phase. The urine excretion of NAG and albumin, reflecting renal dysfunction, was associated with values of both urine IL-6 and IL-8/creatinine quotients, but not with DMSA defects or VUR. Thus, the initial urine IL-6/creatinine quotients might be used as an indicator of risk for persistent renal damage in acute pyelonephritis. PMID- 7885790 TI - The impact of fetal screening on indications for cystourethrography in infants. AB - To evaluate cystourethrography in the era of fetal screening, we evaluated retrospectively the clinical and imaging findings of all children up to the age of 1 year who underwent a cystourethrogram in a 5-year period (1987-1992). There were 292 children, 64 neonates (< 1 month, 51 boys, 13 girls) and 228 infants (1 month-1 year, 111 boys, 117 girls). Hydronephrosis detected prenatally and confirmed after birth by US was the indication for cystourethrography in 88 children (72 boys, 16 girls). This 4.5 to 1, male to female ratio is very unusual compared to children with urinary tract infection, the great majority of whom are girls. The findings based on imaging studies in these 88 children with hydronephrosis included 31 with vesicoureteral reflux (VUR) (in 4 this was secondary), 23 with obstruction at the ureteropelvic junction (UPJ), 13 with multicystic dysplastic kidney, 2 with obstruction at the ureterovesical junction, 1 with ectopic ureterocele and 1 with posterior urethral valves, both the latter without reflux. Eleven children had normal postnatal studies and six children were lost to follow-up. Urinary tract infection (UTI) was the indication in 163 children (62 boys, 101 girls). Forty-one children were examined for other causes. Although most cases of hydronephrosis were detected on fetal screening, UTI was still the most common indication for cystourethrography and some significant abnormalities were found in these symptomatic children. PMID- 7885791 TI - Malpractice in pediatric radiology: a survey in the United States and Canada. AB - A survey of the chairmen of pediatric radiology departments in children's hospitals in Canada and the United States was undertaken to gain data on the subject of malpractice in pediatric radiology. Sixty-two members of the Society of Chairmen of Radiology in Children's Hospitals (SCORCH) were surveyed. Forty two surveys (65%) were returned for analysis. Malpractice premiums paid per pediatric radiologist per year ranged from $499-$29,000 (mean $8,630). Twenty eight malpractice claims were reported from 1980 to 1992. The largest number of claims involved gastrointestinal/abdomen and chest examinations, areas that were perceived as low risk by the respondents. The incidence of lawsuits against pediatric radiologists in the midwest was statistically higher compared to Canada (p < 0.05). Private practice models had a statistically greater incidence of malpractice suits compared to university practice models (p < 0.04). No statistical difference between the number of malpractice suits and the number of examinations performed per year or the number of pediatric radiologists in the group was found. We concluded that pediatric radiologists run the risk of malpractice claims. This data may aid in lessening this risk in the future. PMID- 7885792 TI - Radiological features in congenital camptodactyly, familial arthropathy and coxa vara syndrome. AB - The association of congenital camptodactyly, familial arthropathy and coxa vara is a rare but recognized clinical entity. The radiological manifestations were reviewed in five patients. In the hips, coxa vara, short broad femoral necks and intraosseous cysts were demonstrated in all patients. Abnormal modeling of the acetabulum, increased joint space, effusion, small iliac wings and intraosseous herniation of fluid were found in four out of five patients. Somewhat flat, slightly irregular femoral heads were seen in three patients. In the knees, effusion was demonstrated in all five patients and thick cartilage in three. The elbow, wrist and ankle joints showed abnormal modeling with evidence or suspicion of intraarticular fluid in the majority of patients. Flexion deformities of the fingers were seen in all patients. PMID- 7885793 TI - Subcutaneous granuloma annulare: four cases and review of the literature. AB - Subcutaneous granuloma annulare (SGA) produces benign nodules in otherwise healthy children. The histology of the lesions may be indistinguishable from rheumatoid nodules. However, in children the lesion of SGA is not accompanied by connective-tissue disease. We report 4 patients with SGA. There were three girls and one boy ranging in age from 4 to 15 years. All the children presented with a solitary lesion on the lower limb. A cutaneous lesion was also present in case 4. In only one patient (case 4) was there a history of trauma. There was no relevant past medical history. Routine laboratory tests were normal (including ESR and auto-immune profile). A computed tomography (CT) scan with intravenous contrast was performed in all patients. The CT features were those of soft tissue masses of variable attenuation and enhancement with inconsistent infiltration into surrounding fat. There appear to be no specific CT features which distinguish this benign lesion from a more sinister one. Excisional biopsy was performed in all cases. In children, SGA should be included in the differential diagnosis of soft-tissue masses, particularly in the lower extremity. PMID- 7885794 TI - MRI of petrositis in chronic granulomatous disease. PMID- 7885795 TI - Torsion of an accessory spleen presenting as an acute abdomen with an inflammatory mass. US, CT, and MRI findings. AB - Torsion of an accessory spleen is extremely rare. Only seven cases in children have been reported in the literature. This entity should be considered in the differential diagnosis of acute abdomen associated with an intraperitoneal inflammatory mass. This report describes a 10-year-old boy with severe abdominal pain and a mass that was found to be due to infarction of an accessory spleen that had twisted on its pedicle. Magnetic resonance imaging taken at two different times was helpful in detecting an inflammatory mass, while ultrasonography and computed tomography indicated only the presence of an intraperitoneal mass. PMID- 7885796 TI - Wandering spleen and gastric volvulus. AB - Gastric volvulus and wandering spleen are related to anomalies in the intraperitoneal visceral attachments. When encountered during infancy, they have a congenital origin with acquired predisposing factors. Wandering spleen is a rare clinical entity with a diverse form of presentation. To our knowledge, gastric volvulus associated with wandering spleen has not been reported previously in literature. PMID- 7885797 TI - CT findings in prearterial reversed midgut rotation. AB - A case of pre-arterial reversed midgut rotation is presented. The CT findings of this rare anomaly are discussed. PMID- 7885799 TI - Parental or custodial factors in what is new recognized as child abuse. PMID- 7885798 TI - Calcific pancreatitis-induced gastroduodenal artery pseudoaneurysm: non-surgical management. AB - Hemorrhage associated with pancreatitis has a high morbidity and mortality in the early phase of the illness. In a small number of patients, bleeding is from major pancreatic or peripancreatic vessels which necessitates emergency intervention. However, most such reports are confined to adults. We report a 6-year-old girl with chronic calcific pancreatitis who presented with hematemesis and melena without any acute exacerbation of her underlying illness. Pseudoaneurysm of the gastroduodenal artery was detected by angiography which was then effectively treated at the same time by embolization with gel foam and a steel coil, thus obviating the need for surgical intervention. PMID- 7885800 TI - Pleural effusion: a complication of Gorham's disease. PMID- 7885801 TI - Visual search for singleton feature targets within and across feature dimensions. AB - Three experiments investigated visual search for singleton feature targets. The critical dimension on which the target differed from the nontargets was either known in advance or unknown--that is, the critical difference varied either within a dimension or across dimensions. Previous work (Treisman, 1988) had shown that, while the search reaction time (RT) functions were flat in both conditions, there was an intercept cost for the cross-dimension condition. Experiment 1 examined whether this cost would disappear when responses could be based on the detection of any (target-nontarget) difference in the display (by requiring a "heterogeneity/homogeneity" decision). The cost remained. This argues that pop out requires (or involves) knowledge of the particular dimension in which an odd one-out target differs from the nontargets; furthermore, that knowledge is acquired through the elimination of dimensions not containing a target. In Experiment 2, the subjects had to eliminate (or ignore) one potential source of difference in order to give a positive response (displays could contain a "noncritical" difference requiring a negative response). The result was a comparatively large cost in the within-dimension (positive) condition. This can be taken to indicate that pop-out as such does not make available information as to the particular feature value in which the target differs from the nontargets. Experiment 3 examined whether search priorities can be biased in accordance with advance knowledge of the likely source of difference. The subjects were found to have a high degree of top-down control over what particular dimension to assign priority of checking to. The implication of the results for models of visual search and selection are discussed. PMID- 7885802 TI - Time, change, and motion: the effects of stimulus movement on temporal perception. AB - The effects of stimulus motion on time perception were examined in five experiments. Subjects judged the durations (6-18 sec) of a series of computer generated visual displays comprised of varying numbers of simple geometrical forms. In Experiment 1, subjects reproduced the duration of displays consisting of stationary or moving (at 20 cm/sec) stimulus figures. In Experiment 2, subjects reproduced the durations of stimuli that were either stationary, moving slowly (at 10 cm/sec), or moving fast (at 30 cm/sec). In Experiment 3, subjects used the production method to generate specified durations for stationary, slow, and fast displays. In Experiments 4 and 5, subjects reproduced the duration of stimuli that moved at speeds ranging from 0 to 45 cm/sec. Each experiment showed that stimulus motion lengthened perceived time. In general, faster speeds lengthened perceived time to a greater degree than slower speeds. Varying the number of stimuli appearing in the displays had only limited effects on time judgments. Other findings indicated that shorter intervals tended to be overestimated and longer intervals underestimated (Vierordt's law), an effect which applied to both stationary and moving stimuli. The results support a change model of perceived time, which maintains that intervals associated with more changes are perceived to be longer than intervals with fewer changes. PMID- 7885803 TI - Target and nontarget grouping in visual search. AB - The results of Driver et al. rule out strictly element-by-element approaches to the problem of easy conjunction search. Neither can they be explained by a simple bias toward mismatching display elements, at least as it is implemented in guided search. Such a bias is the only means of within-display interaction in many current models (Sagi & Julesz, 1984; Ullman, 1984). Instead, models (Sagi & Julesz, 1984; Ullman, 1984). Instead, the results suggest that perceptual grouping brings a bias toward common fate. For nontarget groups, this fate is rejection from further consideration; for target groups, complementarily, it is selection for further processing. PMID- 7885804 TI - Detection of heteroquality taste mixtures. AB - Detection thresholds were measured for sweet (sucrose), salty (sodium chloride), sour (citric acid), and bitter (quinine hydrochloride) and for the 11 possible mixtures of these four substances. These 11 mixtures (6 binary, 4 ternary, and 1 quaternary) all turned out to be stimulus additive, in the sense that a person could reliably detect mixtures whose individual components are weaker than their unmixed thresholds. Tastants too weak to be perceived alone can thus make impact when in mixtures. The threshold concentration for a given compound was reduced in approximate proportion to the number of compounds added to it. This liberal heteroquality additivity contests the widespread belief that heteroquality mixtures (different chemicals evoking different qualities) are non-additive and homoquality mixtures (different chemicals evoking the same quality) are additive. Heteroquality additivity emerges on appropriate definition of the subject's task by forced choice (unavailable to earlier investigators), in order to skirt methodological pitfalls. Operating together, homo- and heteroquality additivity may concomitantly enable a person to sense natural mixtures of hosts of weak constituents, such as drinking water. In this regard, gustatory mixtures may function much as do mixtures of frequencies in audition and mixtures of gaseous compounds in olfaction. PMID- 7885805 TI - Magnitude of luminance modulation specifies amplitude of perceived movement. AB - A compelling impression of movement, which is perceptually indistinguishable from a real displacement, can be elicited by patterns containing no spatially displaced elements. An apparent oscillation, w-movement, was generated by a stationary pattern containing a large number of horizontal pairs of spatially adjacent dots modulated in brightness. The observer's task was to adjust the perceived amplitude of the w-motion to match the amplitude of a real oscillation. All of the data can be accounted for by a simple rule: If the relative change in the luminance, W = delta L/L, between two adjacent stationary dots is kept constant, the distance over which these dots appeared to travel in space comprises a fixed fraction of the total distance by which they are separated. The apparent amplitude of the w-motion increases strictly in proportion with luminance contrast, provided that the contrast is represented in the motion encoding system by a rapidly saturating compressive Weibull transformation. These findings can be explained in terms of bilocal motion encoders comparing two luminance modulations occurring at two different locations. PMID- 7885806 TI - Inertial acceleration as a measure of linear vection: an alternative to magnitude estimation. AB - The present study focused on the development of a procedure to assess perceived self-motion induced by visual surround motion--vection. Using an apparatus that permitted independent control of visual and inertial stimuli, prone observers were translated along their head x-axis (fore/aft). The observers' task was to report the direction of self-motion during passive forward and backward translations of their bodies coupled with exposure to various visual surround conditions. The proportion of "forward" responses was used to calculate each observer's point of subjective equality (PSE) for each surround condition. The results showed that the moving visual stimulus produced a significant shift in the PSE when data from the moving surround condition were compared with the stationary surround and no-vision condition. Further, the results indicated that vection increased monotonically with surround velocities between 4 and 40 degrees/sec. It was concluded that linear vection can be measured in terms of changes in the amplitude of whole-body inertial acceleration required to elicit equivalent numbers of "forward" and "backward" self-motion reports. PMID- 7885807 TI - Evidence for a central representation of instrument timbre. AB - An information processing account of perception seeks to delineate the stages of processing through which a stimulus passes and determine the properties of the representation at each stage. Research in phonetic perception has identified two stages, the second of which is thought to encode abstract acoustic attributes of sounds. The present study provided a further test of this proposal by assessing whether nonphonetic stimuli could yield results similar to those obtained with phonetic stimuli. Five selective adaptation experiments were carried out with a trumpet-piano timbre continuum. Two manipulations were used to measure abstract encoding: cross-ear presentation of adaptor and test series, and the use of adaptors that were acoustically different from the continuum end-points. The results provide evidence for an abstract representation of timbre. The similarity of the findings to those in the phonetic adaptation literature is discussed. PMID- 7885809 TI - Differences in influence between pitched-from-vertical lines and slanted-from frontal horizontal lines on egocentric localization. AB - The visual field exerts powerful effects on egocentric spatial localization along both horizontal and vertical dimensions. Thus, (1) prism-produced visual pitch and visual slant generate similar mislocalizations of visually perceived eye level (VPEL) and visually perceived straight ahead (VPSA) and (2) in darkness curare-produced extraocular muscle paresis under eccentric gaze generates similar mislocalizations in VPEL and VPSA that are essentially eliminated by introducing a normal visual field. In the present experiments, however, a search for influences of real visual slant on VPSA to correspond to the influences of visual pitch on VPEL failed to find one. Although the elevation corresponding to VPEL changes linearly with the pitch of a visual field consisting of two isolated 66.5 degrees-long pitched-from-vertical lines, the corresponding manipulation of change in the slant of either a horizontal two-line or a horizontal four-line visual field on VPSA did not occur. The average slope of the VPEL-versus-pitch function across 5 subjects was +0.40 over a +/- 30 degrees pitch range, but was indistinguishable from 0.00 for the VPSA-versus-slant function over a +/- 30 degrees slant range. Possible contributions to the difference between susceptibility of VPEL and VPSA to visual influence from extraretinal eye position information, gravity, and several retinal gradients are discussed. PMID- 7885808 TI - Contextual effects in difference judgments. AB - Manipulating stimulus spacing, stimulus frequency, or stimulus range usually affects intensity judgments. In six experiments, I investigated the locus of analogues of these contextual effects in a "difference" estimation task. When all stimuli elicited the same taste quality, stimulus distribution affected the scale values only when water was included in the stimulus set (Experiments 1-3). When the subjective ranges of two taste qualities were manipulated, different scale values were obtained for the separate qualities in the two conditions (Experiment 4). Manipulation of the expected response distribution did not affect the scale values or the responses (Experiments 5-6). It is concluded that shifts in stimulus distributions or stimulus ranges result in shifts in subjective scale values. The contextual effects can be interpreted as relative shifts of a number of gustatory continua, with water lying on a separate continuum. Proposed is a model for context-dependent judgments, consisting of four stages: stimulus classification, stimulus placement, continuum placement, and continuum projection. PMID- 7885810 TI - Light and dark adaptation of visually perceived eye level controlled by visual pitch. AB - The pitch of a visual field systematically influences the elevation at which a monocularly viewing subject sets a target so as to appear at visually perceived eye level (VPEL). The deviation of the setting from true eye level average approximately 0.6 times the angle of pitch while viewing a fully illuminated complexly structured visual field and is only slightly less with one or two pitched-from-vertical lines in a dark field (Matin & Li, 1994a). The deviation of VPEL from baseline following 20 min of dark adaptation reaches its full value less than 1 min after the onset of illumination of the pitched visual field and decays exponentially in darkness following 5 min of exposure to visual pitch, either 30 degrees topbackward or 20 degrees topforward. The magnitude of the VPEL deviation measured with the dark-adapted right eye following left-eye exposure to pitch was 85% of the deviation that followed pitch exposure of the right eye itself. Time constants for VPEL decay to the dark baseline were the same for same eye and cross-adaptation conditions and averaged about 4 min. The time constants for decay during dark adaptation were somewhat smaller, and the change during dark adaptation extended over a 16% smaller range following the viewing of the dim two-line pitched-from-vertical stimulus than following the viewing of the complex field. The temporal course of light and dark adaptation of VPEL is virtually identical to the course of light and dark adaptation of the scotopic luminance threshold following exposure to the same luminance. We suggest that, following rod stimulation along particular retinal orientations by portions of the pitched visual field, the storage of the adaptation process resides in the retinogeniculate system and is manifested in the focal system as a change in luminance threshold and in the ambient system as a change in VPEL. The linear model previously developed to account for VPEL, which was based on the interaction of influences from the pitched visual field and extraretinal influences from the body-referenced mechanism, was employed to incorporate the effects of adaptation. Connections between VPEL adaptation and other cases of perceptual adaptation of visual direction are described. PMID- 7885811 TI - Local and global processes in surface lightness perception. AB - Various demonstrations show that a target of constant luminance can be made to appear darker in perceived lightness merely by introducing an adjacent region of higher luminance. This has often been interpreted as a manifestation of contrast effects produced by lateral inhibition, a relatively local process. An alternative interpretation holds that the highest luminance in such a display serves as an anchor that defines the white level. This interpretation is global in the sense that the anchor need not be located near any particular target in order to serve as its standard. Edge integration processes have been postulated that would enable such remote comparisons, but there is controversy about the strength of these processes. We report a series of experiments in which local and global processes were assessed. Specifically, we tested whether the introduction of a higher luminance has a greater darkening effect on an adjacent target than on a remote target. We found no difference, suggesting that the darkening effect is a matter of anchoring, not contrast, and that edge integration processes required by anchoring are relatively strong. PMID- 7885812 TI - The time course of recognition of novel melodies. AB - Seven experiments explored the time course of recognition of brief novel melodies. In a continuous-running-memory task, subjects recognized melodic transpositions following delays up to 2.0 min. The delays were either empty or filled with other melodies. Test items included exact transpositions (T), same contour lures (SC) with altered pitch intervals, and different-contour lures (DC); DCs differed from Ts in the pattern of ups and downs of pitch. With this design, we assessed subjects' discrimination of detailed changes in pitch intervals (T/SC discrimination) as well as their discrimination of contour changes (T/DC). We used both artificial and "real" melodies. Artificial melodies differed in conformity to a musical key, being tonal or atonal. After empty delays, T/DC discrimination was superior to T/SC discrimination. Surprisingly, after filled delays, T/SC discrimination was superior to T/DC. When only filled delays were tested, T/SC discrimination did not decline over the longest delays. T/DC performance declined more than did T/SC performance across both empty and filled delays. Tonality was an important factor only for T/SC discrimination after filled delays. T/DC performance was better with rhythmically intact folk melodies than with artificial isochronous melodies. Although T/SC performance improved over filled delays, it did not overtake T/DC performance. These results suggest that (1) contour and pitch-interval information make different contributions to recognition, with contour dominating performance after brief empty delays and pitch intervals dominating after longer filled delays; (2) a coherent tonality facilitates the encoding of pitch-interval patterns of melodies; and (3) the rich melodic-rhythmic contours of real melodies facilitate T/DC discrimination. These results are discussed in terms of automatic and controlled processing of melodic information. PMID- 7885813 TI - Available response choices affect localization of sound. AB - Successful replication of an experiment by Butler and Humanski (1992) showed that listeners are able to proficiently localize sources on a lateral vertical plane on the basis of interaural differences alone. When a lateral horizontal array was included in the test setup, that finding was replicated only for a broadband signal interacting with the pinna, not for ones (lowpass and pure tone) providing only interaural differences. Cross-plane errors conforming to "cones of confusion" were observed for those latter sounds. In a second experiment, response options were made more unconstrained, which clarified the nature of the cross-plane confusions. Lowpass signals from lateral vertical plane sources tend to be heard at or close to the horizon. Measurement of cue values needs to take account of the response options available to listeners, as well as signal properties. PMID- 7885815 TI - Spectral redundancy: intelligibility of sentences heard through narrow spectral slits. AB - The intelligibility of word lists subjected to various types of spectral filtering has been studied extensively. Although words used for communication are usually present in sentences rather than lists, there has been no systematic report of the intelligibility of lexical components of narrowband sentences. In the present study, we found that surprisingly little spectral information is required to identify component words when sentences are heard through narrow spectral slits. Four hundred twenty listeners (21 groups of 20 subjects) were each presented with 100 bandpass filtered CID ("everyday speech") sentences; separate groups received center frequencies of 370, 530, 750, 1100, 1500, 2100, 3000, 4200, and 6000 Hz at 70 dBA SPL. In Experiment 1, intelligibility of single 1/3-octave bands with steep filter slopes (96 dB/octave) averaged more than 95% for sentences centered at 1100, 1500, and 2100 Hz. In Experiment 2, we used the same center frequencies with extremely narrow bands (slopes of 115 dB/octave intersecting at the center frequency, resulting in a nominal bandwidth of 1/20 octave). Despite the severe spectral tilt for all frequencies of this impoverished spectrum, intelligibility remained relatively high for most bands, with the greatest intelligibility (77%) at 1500 Hz. In Experiments 1 and 2, the bands centered at 370 and 6000 Hz provided little useful information when presented individually, but in each experiment they interacted synergistically when combined. The present findings demonstrate the adaptive flexibility of mechanisms used for speech perception and are discussed in the context of the LAME model of opportunistic multilevel processing. PMID- 7885814 TI - The role of fundamental frequency in signaling linguistic stress and affect: evidence for a dissociation. AB - The fundamental frequency (F0) of the voice is used to convey information about both linguistic and affective distinctions. However, no research has directly investigated how these two types of distinctions are simultaneously encoded in speech production. This study provides evidence that F0 prominences intended to convey linguistic or affective distinctions can be differentiated by their influence on the amount of final-syllable F0 rise used to signal a question. Specifically, a trading relation obtains when the F0 prominence is used to convey emphatic stress. That is, the amount of final-syllable F0 rise decreases as the F0 prominence increases. When the F0 prominence is used to convey affect, no trading relation is observed. PMID- 7885816 TI - Temporal summation of 500-Hz tones and octave-band noise bursts in infants and adults. AB - A visually reinforced operant procedure was employed to obtain 2-point threshold duration functions in 7-month-old infants and adults in two experimental paradigms. In Experiment 1, thresholds were determined for 10- and 100-msec, 500 Hz tones and octave-band noise bursts presented in quiet and noise backgrounds. Threshold-duration functions were significantly steeper for infants than for adults under all experimental conditions, and did not differ in slope as a result of differences in either stimulus bandwidth or masking noise. In Experiment 2, thresholds for trains of brief 500-Hz tone pulses were examined in infant and adult subjects. Infant functions were adult-like for integration of multiple pulse stimuli, suggesting that the traditional, long-term process of temporal summation is mature by 7 months of age. Differences between the present results and those previously obtained for 4-kHz stimuli appear to be consistent with the view that different mechanisms are involved in the detection of low- and high frequency signals. PMID- 7885817 TI - Comparison of the effect of onset asynchrony on auditory grouping in pitch matching and vowel identification. AB - Previous experiments have shown that when a slightly mistuned harmonic of a complex tone starts more than about 80 msec before the remaining components, it makes a reduced contribution to the pitch of the complex. This contribution decreases to zero by about 300-msec onset asynchrony. In vowel perception, however, analogous experiments have shown that a much shorter asynchrony (around 40 msec) is enough to ensure that a component does not influence a vowel's phonemic category. The three experiments reported here demonstrate that this difference in the utility of onset time as a grouping cue does not arise because of differences in stimulus structure, but rather is due to the perceptual task. They show that the onset asynchrony needed in a pitch-matching experiment to remove the contribution that a mistuned component makes to the pitch of a vowel is the same as that needed to remove the contribution to the pitch of a flat spectrum complex tone. They further show that a much smaller onset asynchrony is needed to perceptually remove the same harmonic from a vowel for the calculation of vowel quality. The implication of this result for models of auditory grouping is discussed. PMID- 7885818 TI - Cuing mechanisms in auditory signal detection. AB - Detection of auditory signals under frequency uncertainty can be improved by presenting cues to the listeners. Since various cues have been found to differ in effectiveness, three conceivable mechanisms were considered which might account for these differences. Cuing might reduce the number and/or width of the employed auditory filters or listening bands. Also, cues could modulate the precision of frequency tuning of the filters. Psychometric functions were collected in a detection experiment with frequency uncertainty employing three kinds of cues: pure tones whose frequency was identical to that of the signal (iconic cues), complex tones with a missing fundamental equal to the signal (complex cues), and pure tones with a certain frequency relation to the signal (relative cues). Compared with a no-cue condition, all cue types improved detection performance. Fitting models to the data suggests that in the no-cue condition as well as the complex-cue condition, multiple bands were utilized, and that the iconic and relative cues induced single-band listening. There is no indication that accuracy of frequency tuning was responsible for cue-efficiency differences. PMID- 7885819 TI - Temporal interval production and processing in working memory. AB - Short-term memory or working memory has been proposed as a cognitive structure contributing to time estimation. Thus, in a previous experiment, retrieving a stored item during a temporal-interval production lengthened the interval in proportion to the number of items in the memory set. In the present study, this issue was analyzed further by testing whether the proportional lengthening is induced by the load itself (i.e., the number of items) or by comparing the probe with memorized items. In a first experiment, a memory set was maintained during a temporal production, and the comparison of the probe with memorized items was postponed until the end of time production. Varying the number of items in the memory set had no effect on temporal intervals produced during its retention, suggesting that mental comparison was the source of the lengthening of time intervals. In succeeding experiments, tasks requiring processing in working memory but involving no memory load were combined with temporal production. In Experiment 2, increasing the number of syllables in a rhyme-judgment task proportionally lengthened temporal intervals that were produced simultaneously. In Experiment 3, increasing the amount of mental rotation in a task involving visuospatial processing also lengthened simultaneous temporal production. This interference between processing in working memory and time estimation suggests that working memory, defined as a work space for active processing of current information, contributes to time estimation. PMID- 7885820 TI - Does perceived size depend on perceived distance? An argument from extended haptic perception. AB - Two experiments were directed at the comparison between two perspectives on the perception of size achieved by probing the gap between two occluded distal surfaces by means of a hand-held rod. One perspective was the classical size distance invariance hypothesis developed for the problem of visual size perception with a central role for perceived distance; the other was the hypothesis that the extended haptic perception of gap size is specific to a physical invariant lambda of the dynamics of probing. Experiment 1 examined the relation between hepatically perceived gap size and haptically perceived gap distance. No causal connection between the two was found, and all the variance in perceived size was accounted for by lambda. Experiment 2 manipulated the rotational inertia of the probe. Its effect was different for the two perceptions of size and distance, underscoring their independence. The indifference of perceived size to perceived distance was discussed in reference to identifying invariants for both the haptic and the visual perception of size at a distance. PMID- 7885821 TI - Illumination change at a depth edge can reduce lightness constancy. AB - Lightness constancy requires that a surface retain its lightness not only when the illumination is changed but also when the surface is moved from one background to another. Occlusion of one surface by another frequently results in a retinal juxtaposition of patches under different illuminations. At such edges, retinal luminance ratios can be much higher than in scenes with a single illumination. We demonstrate that such retinal adjacencies can produce failures of lightness constancy. We argue that they are responsible for departures from perfect lightness constancy in two prior experiments that examined the effects of depth relations on lightness constancy. PMID- 7885822 TI - Perceptual and cognitive processes in time-to-contact estimation: analysis of prediction-motion and relative judgment tasks. AB - Three classes of task appear to involve time-to-contact (TTC) information: coincidence anticipation (CA) tasks, relative judgement (RJ) tasks, and interceptive actions (IAs). An important type of CA task used to study the perception of TTC is the prediction-motion (PM) task. The question of whether it is possible to study the perceptual processes involved in the timing of IAs using PM and RJ tasks is considered. A revised version of the tau hypothesis is proposed as an account of the perceptual information processing involved in the control of fast IAs. This draws on the distinction between "motor" and "cognitive" visual systems. It is argued that task variables affect whether "cognitive" information processing is involved in performance and can determine whether TTC information is used at all. Evidence is reviewed that suggests that PM and RJ tasks involve cognitive processing. It is argued that target viewing time, TTC at response initiation, amount of practice, and whether there is a period between target disappearance and response are task variables that determine whether cognitive processing will influence responding. PMID- 7885823 TI - A model for realism of confidence judgments: implications for underconfidence in sensory discrimination. AB - In a recent issue of this journal, Bjorkman, Justlin, and Winman (1993) presented a model of the calibration of subjective confidence judgments for sensory discrimination which they called "subjective distance theory." They proposed that there was a robust underconfidence bias in such judgments, that the model predicted such a bias, and that two different models were needed for the calibration of subjective confidence for cognitive judgments and for sensory ones. This paper addresses issues they raised. It points out that they have not presented a new model, but rather a portion of a more general one, the "decision variable partition model" originally proposed in Ferrell and McGoey (1980). This paper explores properties of the model and shows, contrary to Bjorkman, Juslin, and Winman's hypotheses, that the model does not predict underconfidence, that the "hard-easy effect" can be observed with sensory discriminations, and that the model fits not only sensory, but also cognitive judgments. PMID- 7885824 TI - Functional characterization of the cis-regulatory elements of the rat ribophorin I gene. AB - The ribophorin I gene encodes a rough endoplasmic reticulum (RER) specific membrane protein which is a subunit of the oligosaccharyltransferase. To establish the functional activity of its promoter region we have performed transient gene transcription experiments employing plasmid constructs that contain 5' flanking regions of the ribophorin I gene cloned upstream of the CAT reporter gene. Among the restriction fragments obtained from the 1.3-kilobase 5' flanking region, a proximal fragment (-42 to +24) containing two GC-rich elements was required for basic promoter activity, while a fragment (-364 to +24) encoding an additional GC-box and an octamer like motif at -233 conferred the maximal promoter activity. In order to investigate the functionality of an octomer-like sequence co-transfection experiments were performed with Oct-2 cDNA and the CAT reporter gene containing the ribophorin I fragment (-364 to +24). A 3-4-fold increase in the transcriptional activity was observed with this construct. In addition, gel shift experiments showed Oct-2 binding to this construct. These results indicate that Oct-2 is most likely involved in the regulation of the ribophorin I gene transcription. We suggest that the GC-rich elements are necessary for constitutive ribophorin I expression while octamer motif binding proteins function synergistically with the GC-rich element binding proteins to increase the expression of the ribophorin I gene during the proliferation of RER. PMID- 7885825 TI - Interaction of the yeast splicing factor PRP8 with substrate RNA during both steps of splicing. AB - PRP8 protein of Saccharomyces cerevisiae interacts directly with pre-mRNA in spliceosomes, shown previously by UV-crosslinking. To analyse at which steps of splicing and with which precursor-derived RNA species the interaction(s) take place, UV-crosslinking was combined with PRP8-specific immunoprecipitation and the coprecipitated RNA species were analysed. Specific precipitation of intron exon 2 and excised intron species was observed. PRP8 protein could be UV crosslinked to pre-mRNA in PRP2-depleted spliceosomes stalled before initiation of the splicing reaction. Thus, the interaction of PRP8 protein with substrate RNA is established prior to the first transesterification reaction, is maintained during both steps of splicing and continues with the excised intron after completion of the splicing reaction. RNase T1 treatment of spliceosomes revealed that substrate RNA fragments of the 5' splice site region and the branchpoint-3' splice site region could be coimmunoprecipitated with PRP8 specific antibodies, indicating that these are potential sites of interaction for PRP8 protein with substrate RNA. Protection of the branch-point-3' splice site region was detected only after step 1 of splicing. The results allow a first glimpse at the pattern of PRP8 protein-RNA interactions during splicing and provide a fundamental basis for future analysis of these interactions. PMID- 7885826 TI - Transcriptional activation of the nuclear receptor RZR alpha by the pineal gland hormone melatonin and identification of CGP 52608 as a synthetic ligand. AB - Many important physiological functions are controlled by hormones via binding and activating members of the nuclear receptor superfamily. This group of structurally related transcription factors also includes a still growing number of orphan receptors for which no ligand is known so far. The identification of ligands for orphan receptors is a key to understanding their physiological role, as has been successfully shown for retinoid X receptors and the discovery of 9 cis retinoic acid as a specific ligand. We have discovered very recently that the pineal gland hormone melatonin is a specific ligand for the brain-specific nuclear receptor RZR beta. Here we report that the alpha-subtype of RZR, RZR alpha and its splicing variant ROR alpha 1, is also a nuclear receptor for melatonin with binding specificities in the low nanomolar range. In contrast to RZR beta, RZR/ROR alpha is expressed in many tissues and cells outside the brain. We found that RZR alpha and ROR alpha 1 vary in their constitutive transactivational activity and are activated to a different extent by melatonin. Furthermore, we identified a synthetic RZR-ligand, the thiazolidine dione CGP 52608. This compound is a functional analogue of melatonin at its nuclear receptor, but does not bind to the high affinity membrane receptor for melatonin. Therefore, this specific RZR-ligand may help to differentiate between nuclear and membrane signalling of melatonin. PMID- 7885827 TI - Proteolytic cleavage of initiation factor eIF-4 gamma in the reticulocyte lysate inhibits translation of capped mRNAs but enhances that of uncapped mRNAs. AB - Infection of cells with the foot-and-mouth-disease virus, a member of the picornavirus family, results in the shut-off of host protein synthesis. A major contributory mechanism is the proteolytic destruction of the gamma subunit of the complex eIF-4, which functions in translation to promote the binding of the 43S ribosomal preinitiation complex to the 5' end of the cellular mRNA molecules bearing a 5' terminal cap structure. Picornavirus RNA molecules, which are uncapped, use a distinct mechanism for translational initiation, which can operate in the absence, or at low levels, of eIF-4. The proteolysis of eIF-4 gamma in cells infected by foot-and-mouth-disease virus results from expression of a virus-encoded cysteine proteinase known as Leader (or L) protease. We have used a transcription plasmid encoding this protease as a tool to deplete in vitro translation systems of eIF-4 gamma in order to elucidate in more detail the role of this polypeptide in the control of translation. Using in vitro transcribed mRNAs we have observed a marked contrast between capped and uncapped transcripts in the response of their translation to the proteolysis of eIF-4 gamma. Translation of capped mRNAs is, as expected, severely impaired, and is restored by addition of eIF-4 complex containing the intact gamma-subunit. On the other hand, translation of uncapped transcripts, normally inefficient, is substantially enhanced. The data suggest that the translation of uncapped mRNAs may be stimulated in this system by one or more of the proteolytic degradation products of eIF-4 gamma. PMID- 7885828 TI - Divalent metal ion binding to a conserved wobble pair defining the upstream site of cleavage of group I self-splicing introns. AB - The upstream site of cleavage of all group I self-splicing introns is identified by an absolutely conserved U.G base pair. Although a wobble C.A pair can substitute the U.G pair, all other combinations of nucleotides at this position abolish splicing, suggesting that it is an unusual RNA structure, rather than sequence, that is recognized by the catalytic intron core. RNA enzymes are metalloenzymes, and divalent metal ion binding may be an important requirement for splice site recognition and catalysis. The paramagnetic broadening of NMR resonances upon manganese binding at specific sites was used to probe the interaction between divalent metal ions and an oligonucleotide model of a group I intron ribozyme substrate. Unlike previous studies in which only imino proton resonances were monitored, we have used isotopically labelled RNA and a set of complete spectral assignments to identify the location of the divalent metal binding site with much greater detail than previously possible. Two independent metal binding sites were identified for this oligonucleotide. A first metal binding site is located in the major groove of the three consecutive G.C base pairs at the end of double helical stem. A second site is found in the major groove of the RNA double helix in the vicinity of the U.G base pair. These results suggest that metal ion coordination (or a metal bridge) and tertiary interactions identified biochemically, may be used by group I intron ribozymes for substrate recognition. PMID- 7885829 TI - Identification of close contacts between the sigma N (sigma 54) protein and promoter DNA in closed promoter complexes. AB - The complexes forming between the alternative sigma factor protein sigma N (sigma 54), its holoenzyme and promoter DNA were analysed using the hydroxyl radical probe and by photochemical footprinting of bromouridine-substituted DNA. Close contacts between the promoter, sigma N and its holoenzyme appear to be restricted predominantly to one face of the DNA helix, extending from -31 to -5. They all appear attributable to sigma N and no extra close contacts from the core RNA polymerase subunits in the holoenzyme-promoter DNA complex were detected. We suggest that the apparent absence of close core RNA polymerase contacts in the region of the promoter DNA to be melted during open complex formation is important for maintaining the closed complex. Results of the hydroxyl radical footprinting imply that sigma N makes multiple DNA backbone contacts across and beyond the -12, -24 consensus promoter elements, and the photochemical footprints indicate that consensus thymidine residues contribute important major groove contacts to sigma N. Formation of the open complex is shown to involve a major structural transition in the DNA contacted by sigma N, establishing a direct role for sigma N in formation of the activated promoter complex. PMID- 7885830 TI - Characterization of cDNA encoding mouse homolog of fission yeast dhp1+ gene: structural and functional conservation. AB - The dhp1+ gene of Schizosaccharomyces pombe is a homolog of Saccharomyces cerevisiae HKE1/RAT1/TAP1 gene that is involved in RNA metabolism such as RNA trafficking and RNA synthesis. dhp1+ is also related to S. cerevisiae DST2 (SEP1) that encodes a DNA strand exchange protein required for sporulation and homologous recombination in S.cerevisiae. We isolated several clones of Dhm1, a mouse homolog of dhp1+, from mouse spermatocyte cDNA library and determined its nucleotide sequence. The Dhm1 gene consists of an open reading frame predicting a protein with 947 amino acids and molecular weight of 107,955. Northern blot analysis revealed that Dhm1 is transcribed at high level in testis, liver and kidney. The predicted product of Dhm1 (Dhm1p) has a significant homology with Dhp1p, Hke1p/Rat1p/Tap1p and Dst2p. In particular, Dhm1p, Dhp1p and Hke1p/Rat1p/Tap1p share strong similarity at the two regions of their N- and C terminal parts. The Dhm1 gene on a multicopy plasmid rescued the temperature sensitivity of dhp1ts and lethality of dhp1 null mutation, suggesting that Dhm1 is a mouse homolog of S.pombe dhp1+ and functions similarly in mouse as dhp1+. PMID- 7885831 TI - p53 binds single-stranded DNA ends through the C-terminal domain and internal DNA segments via the middle domain. AB - We have previously reported that wild-type p53 can bind single-stranded (ss) DNA ends and catalyze renaturation of ss complementary DNA molecules. Here we demonstrate that p53 can also bind to internal segments of ss DNA molecules via a binding site (internal DNA site) distinct from the binding site for DNA ends (DNA end site). Using p53 deletion mutants, the internal DNA site was mapped to the central region (residues 99-307), while the DNA end site was mapped to the C terminal domain (residues 320-393) of the p53 protein. The internal DNA site can be activated by the binding of ss DNA ends to the DNA end site. The C-terminal domain alone was sufficient to catalyze DNA renaturation, although the central domain was also involved in promotion of renaturation by the full-length protein. Our results suggest that the interaction of the C-terminal tail of p53 with ss DNA ends generated by DNA damage in vivo may lead to activation of non-specific ss DNA binding by the central domain of p53. PMID- 7885832 TI - Rho-independent terminators without 3' poly-U tails from the early region of actinophage oC31. AB - Previous work has identified three intergenic regions from the early region of actinophage oC31 where transcription was either terminated or the mRNA was processed. Here we show using in vivo and in vitro approaches that these regions contain rho-independent terminators designated eta, etb and etc. Transcripts through eta-c would be expected to form stable RNA stem-loops but would lack poly U tails. Eta-c contained part or all of the conserved sequences 5' AGCCCC and 5' GGGGCTT. A Streptomyces 'terminator probe' vector, pUGT1, was constructed and used to assay the efficiency of termination of transcription by eta-c from the thiostrepton-inducible tipA promoter by measuring the expression of a downstream reporter gene (aphII). In pUGT1 etb was at best a minor terminator in vivo whilst eta and etc exhibited strong termination activity. In vitro termination was assayed using templates containing a synthetic promoter recognised by E.coli RNA polymerase and fragments containing eta-c inserted downstream. All three terminators stimulated the formation of 3' ends in the promoter-distal arm of the inverted repeats with efficiencies eta > etc > etb. As all three terminators either overlap with or lie close to sequences which interact with phage repressor proteins (conserved inverted repeats, CIRs) and these can potentially form stem loop structures in RNA, the effect of CIRs on termination was also investigated. Termination at etb was unaffected by the presence or absence on the transcription template of CIR3. CIR4 forms the central 17 bp of etc and a 37 nt deletion which eliminated this stem-loop abolished termination in vivo and in vitro. Eta was investigated using an antisense oligonucleotide interference assay; an oligo designed to bind the 5' arm of eta inhibited termination whilst an oligo antisense to CIR5 was ineffective and an oligo targeted further upstream enhanced termination. Taken together these data show that eta-c are intrinsic, rho independent terminators of varying efficiencies despite the absence of a poly-U tail. PMID- 7885833 TI - Localization of binding site for encephalomyocarditis virus RNA polymerase in the 3'-noncoding region of the viral RNA. AB - We previously showed that encephalomyocarditis (EMC) virus RNA-dependent RNA polymerase (3Dpol) binds specifically to 3'-terminal segments of EMC virus RNA. This binding, which depends on both the 3'-noncoding region (3'-NCR) and 3'-poly (A) tail [together denoted 3'-NCR(A)], may be an important step in the initiation of virus replication. In this paper, the 3'-NCR and 3'-poly(A) were separately transcribed then mixed, but no complex with 3Dpol was obtained, showing that covalent attachment of the 3'-poly(A) to the 3'-NCR is essential for complex formation. Mutational and deletion analyses localized a critical determinant of 3Dpol binding to a U-rich sequence located 38-49 nucleotides upstream of the 3' poly(A). Similar analyses led to the identification of a sequence of A residues between positions +10 and +15 of the 3'-poly(A) which are also critical for 3Dpol binding. As U-rich and A-rich regions are important for 3Dpol binding, a speculative model is proposed in which 3Dpol induces and stabilizes the base pairing of the 3'-poly(A) with the adjacent U-rich sequence to form an unusual pseudoknot structure to which 3Dpol binds with high affinity. PMID- 7885834 TI - Cloning and characterisation of the Schizosaccharomyces pombe rad32 gene: a gene required for repair of double strand breaks and recombination. AB - A new Schizosaccharomyces pombe mutant (rad32) which is sensitive to gamma and UV irradiation is described. Pulsed field gel electrophoresis of DNA from irradiated cells indicates that the rad32 mutant, in comparison to wild type cells, has decreased ability to repair DNA double strand breaks. The mutant also undergoes decreased meiotic recombination and displays reduced stability of minichromosomes. The rad32 gene has been cloned by complementation of the UV sensitive phenotype. The gene, which is not essential for cell viability and is expressed at a moderate level in mitotically dividing cells, has significant homology to the meiotic recombination gene MRE11 of Saccharomyces cerevisiae. Epistasis analysis indicates that rad32 functions in a pathway which includes the rhp51 gene (the S.pombe homologue to S.cerevisiae RAD51) and that cells deleted for the rad32 gene in conjunction with either the rad3 deletion (a G2 checkpoint mutation) or the rad2 deletion (a chromosome stability and potential nucleotide excision repair mutation) are not viable. PMID- 7885835 TI - Identity elements of Saccharomyces cerevisiae tRNA(His). AB - Recognition of tRNA(His) by Saccharomyces cerevisiae histidyl-tRNA synthetase was studied using in vitro transcripts. Histidine tRNA is unique in possessing an extra nucleotide, G-1, at the 5' end. Mutation studies indicate that this irregular secondary structure at the end of the acceptor stem is important for aminoacylation with histidine, while the requirement of either base of this extra base pair is smaller than that in Escherichia coli. The anticodon was also found to be required for histidylation. The regions involved in histidylation are essentially the same as those in E.coli, whereas the proportion of the contributions of the two portions distant from each other, the anticodon and the end of the acceptor stem, makes a substantial difference between the two systems. PMID- 7885836 TI - Promoter control of translation in Xenopus oocytes. AB - The HIV-1 promoter directs the high level production of transcripts in Xenopus oocytes. However, despite being exported to the cytoplasm, the transcripts are not translated [M. Braddock, A. M. Thorburn, A. Chambers, G. D. Elliott, G. J. Anderson, A. J. Kingsman and S. M. Kingsman (1990) Cell, 62, 1123-1133]. We have shown previously that this is a function of promoter sequences and is independent of the TAR RNA element that is normally located at the 5' end of all HIV mRNAs. We now show that a three nucleotide substitution at position -340, upstream of the RNA start site, reverses the translation inhibition. This site coincides with a sequence that can bind the haematopoietic transcription factor GATA. The inhibition of translation can also be reversed by treatment with inhibitors of casein kinase II or by injection into the nucleus of antibodies specific for the FRGY2 family of RNP proteins. We suggest that the -340 site influences the quality of the transcription complex such that transcripts are diverted to a nucleus-dependent translation inhibition pathway. PMID- 7885837 TI - Nuclear degradation of nonsense mutated beta-globin mRNA: a post-transcriptional mechanism to protect heterozygotes from severe clinical manifestations of beta thalassemia? AB - Nonsense mutations of the beta-globin gene are a common cause of beta thalassemia. It is a hallmark of these mutations not only to cause a lack of protein synthesis but also a reduction of mRNA expression. Both the pathophysiologic significance and the underlying mechanisms for this surprising phenomenon have so far remained enigmatic. We report that the reduction of the fully spliced mutant beta-globin mRNA already manifests itself within the nucleus. In contrast, the levels of mutant pre-mRNA are normal. The promoter and the 5'-untranslated region (5'-UTR) of the herpes simplex virus type 1 thymidine kinase (HSV1 Tk) gene can independently circumvent this recognition/response mechanism in cis and restore nonsense mutated beta-globin mRNA expression to normal levels. These two genetic elements can thus exert a dominant influence on the post-transcriptional control of nonsense mutated beta-globin gene expression. While wild-type mRNA levels are restored by fusion of the HSV1 Tk 5'-UTR to the nonsense mutated beta-globin reading frame, translation of a wildtype reading frame in such a hybrid is precluded. In contrast, the HSV1 Tk promoter appears to efficiently deliver the mRNA to the translational apparatus. The 5'-UTR and the promoter sequences therefore control the nuclear fate of nonsense mutated beta globin mRNA by separable pathways. The nuclear mRNA degradation mechanisms examined here may prevent the synthesis of C-terminally truncated beta-globin chain fragments and may protect heterozygotes from clinically relevant symptoms of beta-thalassemia. PMID- 7885838 TI - Homodimer of p50 (NF kappa B1) does not introduce a substantial directed bend into DNA according to three different experimental assays. AB - Transcription factors can distort the conformation of the DNA double helix upon binding to their target sites. Previously, studies utilizing circular permutation -electrophoretic mobility shift assay suggested that the homodimer of p50 (NF kappa B1), canonical NF-kappa B (p65-p50), as well as several non-canonical NF kappa B/Rel complexes, may induce substantial DNA bending at the binding site. Here we have applied three additional experimental approaches, helical phasing analysis, minicircle binding and cyclization kinetics, and conclude that the homodimer of p50 introduces virtually no directed bend into the consensus kappa B sequences GGGACTTTCC or GGGAATTCCC. PMID- 7885840 TI - Protection of DNA sequences by triplex-bridge formation. AB - We have demonstrated that the DNA sequence between two triplex-forming polypurine.polypyrimidine (Pu.Py) tracts was protected from DNA modifying enzymes upon formation of triplex DNA structures with an oligodeoxyribonucleotide in which two triplex-forming Pu or Py tracts were placed at the termini (triplex bridge formation). In model experiments, when two triplex structures were formed between double-stranded DNA with the sequence (AG)17-(N)18-(T)34, and an oligodeoxyribonucleotide, (T)34-(N)18-(GA)17, not only the Pu.Py tracts but also the 18 bp non-Pu.Py sequence in the duplex DNA between the tracts was protected from restriction enzymes, HpaII methylase and DNase I. This protection occurred only when both of the Pu.Py tracts were involved as triplexes. The length of the tracts could be as short as 21 bp, while the difference in length between the non Pu.Py sequences on the duplex and the oligodeoxyribonucleotide should be within 10 nucleotides. The efficiency of protection was enhanced in the presence of a cationic detergent, cetyltrimethylammonium bromide, during triplex formation. Protection was also observed with another type of the triplex bridge formed between (G)34 and (T)34 tracts with an oligodeoxyribonucleotide, (T)34-(N)20 (G)34. These findings suggest that the protection of specific DNA sequences from enzymes by triplex-bridge formation can be applied to any DNA sequence by placing it between two triplex-forming sequences. PMID- 7885839 TI - Lens-specific activity of the mouse alpha A-crystallin promoter in the absence of a TATA box: functional and protein binding analysis of the mouse alpha A crystallin PE1 region. AB - Lens-specific expression of the mouse alpha A-crystallin gene is regulated at the level of transcription. Here, we have studied the role of the PE1 region, which contains the TATA box (-31/-26) and the immediately adjacent PE1B sequence (-25/ 12), in transcriptional regulation. Deletions within either the TATA box or PE1B sequence eliminated promoter activity in transfected lens cells. Surprisingly, these deletions did not eliminate lens-specific promoter activity of the transgene of transgenic mice. Transcription of the transgene with a TATA-deleted promoter initiated at multiple sites in the lenses of the transgenic mice. Footprint analysis revealed that the entire PE1 region was protected by nuclear extracts prepared from lens cells which express the alpha A-crystallin gene and from fibroblasts which do not express the gene. The -37/+3 region formed three specific EMSA complexes using lens cell nuclear extracts, while a similar but much less intense pattern was observed when a fibroblast nuclear extract was used. Competition experiments indicated that these complexes were not due to the binding of TBP to the TATA box, but rather to the binding of other nuclear proteins to the PE1B -25/-19 region. A series of co-transfection competition studies in vivo also suggested the functional importance of proteins binding in the -25/-19 region. The PE1B protein-DNA interactions appear to be conserved in the chicken, rodent and human alpha A-crystallin gene as well as within the alpha A- and alpha B-crystallin genes in the mouse. Our findings indicate that the PE1B region is important for mouse alpha A-crystallin promoter activity; the proximity of this site to the TATA box raises the possibility for cooperativity or competition between TBP and PE1B-bound proteins. PMID- 7885842 TI - A new mutation in 16S rRNA of Escherichia coli conferring spectinomycin resistance. AB - We report a novel mutation, C1066U in 16S rRNA which was selected for resistance to spectinomycin, an antibiotic which inhibits ribosomal translocation. The minimal inhibitory concentration (MIC) of spectinomycin determined for this mutant (15 micrograms/ml) is greater than with the wild-type plasmid (5 micrograms/ml) but lower than with the well known C1192U mutation (> 80 micrograms/ml). The C1066U mutation also increases the cells sensitivity to fusidic acid, another antibiotic which inhibits translation at the translocation stage, whereas C1192U is unchanged relative to the wild type. We discuss why the acquisition of resistance to one of these drugs is often associated with hypersensitivity to the other. PMID- 7885841 TI - The genomic structure of the STAT genes: multiple exons in coincident sites in Stat1 and Stat2. AB - The genomic structure of Stat2 has been determined and compared with a large portion of the Stat1 gene. There are 24 exons in the Stat2 gene and a matching number in very similar positions in the Stat1 gene. Thus a very complicated genomic structure was presumably duplicated and has been closely maintained throughout evolution. PMID- 7885843 TI - Complex expression of murine heat shock transcription factors. AB - A central step in the transcriptional activation of heat shock genes is the binding of the heat shock factor (HSF) to upstream heat shock elements (HSEs). In vertebrates, HSF1 mediates the ubiquitous response to stress stimuli, while the role of a second HSE-binding factor, HSF2, is still unclear. In this work we show that both factors are expressed in a wide range of murine tissues and each exists as two splicing isoforms. Although HSFs are virtually ubiquitous proteins, their abundance is predominant in testis and variable among other tissues, indicating specific regulations of their expression. A low level of DNA-binding activity of HSF1, detected in many tissues, is probably physiological and is not explained by an anomalous regulation of one of the two isoforms. Our observations suggest that these regulatory proteins may all have roles in fully developed tissues. This possibility is not mutually exclusive of a role of HSF2 during cellular differentiation and tissue development [L. Sistonen, K. D. Sarge and R. I. Morimoto (1994), Mol. Cell. Biol., 14, 2087-2099]. PMID- 7885844 TI - Identification of a 68 kDa protein species as a specific DNA-binding component of the H3abp complex interacting with the histone H3.2 G1/S regulatory domain. AB - The hamster histone H3.2 promoter contains a protein binding site (referred to as site X) required for G1/S transcriptional activation. We report here that nuclear extracts prepared from serum synchronized cells at various stages of the cell cycle show a biphasic increase in the H3.2 specific complex, H3abp, binding to site X. An increase in binding activity occurs as cells first enter the cell cycle and later at the G1/S border. The H3.2 specific binding activity is enhanced by Mg2+ and Ca2+ in vitro, but is inhibited by Zn2+. Site X resembles a Jun/AP-1 site, but previously it has been shown that the H3abp complex is immunologically distinct from the characterized AP-1 proteins. Here, we identify the size of the hamster nuclear protein(s) that bind specifically to the H3abp site by ultra-violet crosslinking and renaturation of specific protein bands following gel electrophoresis. In addition, we purify H3abp by affinity chromatography and show that the purified H3abp has a different methylation interference profile from AP-1. Our results indicate that a protein species around 68 kDa is the major DNA binding component of the H3abp complex and it binds specifically to the histone promoter site required for G1/S regulation. PMID- 7885845 TI - Intra-chromosomal rearrangements generated by Cre-lox site-specific recombination. AB - Chromosomal rearrangements are useful genetic and breeding tools but are often difficult to detect and characterize. To more easily identify and define chromosome deletions and inversions, we have used the bacteriophage P1 Cre-lox site-specific recombination system to generate these events in plants. This involves three steps: (i) the introduction of two lox sites into one locus in a plant genome, including one site within a modified Ds transposon; (ii) Ac transposase-mediated transposition of the Ds-lox element to a new locus on the same chromosome; (iii) Cre-mediated site-specific recombination between the two lox sites that bracket a chromosome segment. We report the production of a deletion and three inversion events in tobacco. The utility of chromosomal segments bracketed by lox sites for targeted manipulation and cloning is discussed. PMID- 7885847 TI - Insertion site specificity of the transposon Tn3. AB - The Tn3-deletion method [Davies and Hutchison, Nucleic Acids Res. 19, 5731-5738, (1991)] was used to sequence a 9.4 kb DNA fragment. Transpositional 'warm' spots were not a limiting factor but a 935 bp 'cold' spot was completed using a synthetic oligonucleotide primer. Two hundred and twenty three miniTn3 insertion sites from three sequencing projects were aligned and a 19 bp asymmetric consensus site was identified. There is no absolute sequence requirement at any position in this consensus, so insertion occurs promiscuously (approximately 37% of sites are potential targets). In our sequencing projects, multiply targeted sites always closely matched the consensus, although not all close matches were targeted frequently. The 935 bp cold spot showed no unusual features when analysed with the consensus sequence. The consensus can be used to accurately predict likely insertion sites in a new sequence. Synthetic oligonucleotides based on the consensus and a known hot spot for Tn3 were mutagenised. These sequences were not hot spots in our vectors, suggesting that the primary sequence alone is not sufficient to create an insertional hot spot. We conclude that some other factor, such as DNA secondary structure, also plays an important role in target site selection for the transposon Tn3. PMID- 7885846 TI - An RNA tertiary structure of the hepatitis delta agent contains UV-sensitive bases U-712 and U-865 and can form in a bimolecular complex. AB - Genomic RNA of the hepatitis delta agent has a highly conserved element of local tertiary structure. This element contains two nucleotides which become covalently crosslinked to each other upon irradiation with UV light. Using direct RNA analysis, we now identify the two nucleotides as U-712 and U-865 and show that the UV-induced crosslink can be broken by re-exposure to a 254 nm peak UV light source. In the rod-like secondary structural model of delta RNA, nucleotides U 712 and U-865 are off-set from each other by 5-6 bases, a distance too great to permit crosslinking. This model needs to be modified. Our data indicate that bases U-712 and U-865 closely approximate each other and suggest that the smooth helical contour proposed for delta RNA is interrupted by the UV-sensitive element. The nucleotide sequence shows that the UV-sensitive site does not have a particularly high density of conventional Watson-Crick base pairs compared to the rest of the genome. However, this element may have a number of non-Watson-Crick bonds which confer stability. Following UV-crosslinking and digestion with 1 mg/ml of RNase T1 at 37 degrees C for 45 min in 10 mM Tris-HCl, 1 mM EDTA (conditions expected to give complete digestion), this element can be isolated as part of a 54 nucleotide long partial digestion product containing at least 16 internal G residues. UV-crosslinking analysis shows that this unusual tertiary structural element can form in a bimolecular complex. PMID- 7885848 TI - Theoretical analysis of DNA intrastrand cross linking by formation of 8,5' cyclodeoxyadenosine. AB - Formation of intramolecular cross links by addition of C(5') deoxyribose radicals to the C(8)-N(7) double bond of an attached adenine base was analyzed by ab initio quantum-chemical methods. Conformational preferences that influence the stereospecificity of the reaction were investigated. A good correlation was found between the ratio of experimental yields of R and S stereoisomers of 8,5' cyclodeoxyadenosine and the relative energy of conformations of the C(5') radical that are precursors to these isomers. Molecular mechanics based on the AMBER force field was used to model the effect of 8,5'-cyclodeoxyadenosine on the conformation of the DNA dodecamer d(CGCGAATTCGCG)2 with the lesion at the A6 position. The R and S stereoisomers of the intrastrand cross link cause comparable levels of DNA distortion with the major conformational changes occurring in backbone torsional angles at the site of the lesion. PMID- 7885849 TI - High sensitivity multianalyte immunoassay using covalent DNA-labeled antibodies and polymerase chain reaction. AB - A multianalyte immunoassay for simultaneous detection of three analytes (hTSH, hCG and beta-Gal) has been demonstrated using DNA-labeled antibodies and polymerase chain reaction (PCR) for amplification of assay response. The labeled antibodies were prepared by covalently coupling uniquely designed DNA oligonucleotides to each of the analyte-specific monoclonal antibodies. Each of the DNA oligonucleotide labels contained the same primer sequences to facilitate co-amplification by a single primer pair. Assays were performed using a two antibody sandwich assay format and a mixture of the three DNA-labeled antibodies. Dose-response relationships for each analyte were demonstrated. Analytes were detected at sensitivities exceeding those of conventional enzyme immunoassays by approximately three orders of magnitude. Detection limits for hTSH, beta-Gal and hCG were respectively 1 x 10(-19), 1 x 10(-17) and 1 x 10(-17) mol. Given the enormous amplification afforded by PCR and the existing capability to differentiate DNA based on size or sequence differences, the use of DNA-labeled antibodies could provide the basis for the simultaneous detection of many analytes at sensitivities greater than those of existing antigen detection systems. These findings in concert with previous reports suggest this hybrid technology could provide a new generation of ultra-sensitive multianalyte immunoassays. PMID- 7885850 TI - Analysis of oligo(deoxynucleoside phosphorothioate)s and their diastereomeric composition. AB - Short oligo(deoxynucleoside phosphorothioate)s were analyzed as a pool of individual diastereomeric species. The composition of such mixtures, determined by means of HPLC, indicates that consecutive couplings in commonly used phosphoramidite chemistry lead to increasing contents of the Rp isomer. Methods of analysis and mathematical basis for diastereomeric composition are discussed. Data presented include all 16 possible combinations of nucleosides in dinucleotide phosphorothioates, as well as examples of trimers and tetramers. PMID- 7885851 TI - Abundant, easy and reproducible production of single-stranded DNA from phagemids using helper phage-infected competent cells. PMID- 7885852 TI - A recombinatorial method useful for cloning dominant alleles in Saccharomyces cerevisiae. PMID- 7885853 TI - The use of K(+)-free buffers eliminates a common cause of premature chain termination in PCR and PCR sequencing. PMID- 7885854 TI - Advanced practice: the options. PMID- 7885855 TI - Facilitating transitions: redefinition of the nursing mission. PMID- 7885856 TI - Witnesses to suffering: nursing knowledge, voice, and vision. PMID- 7885857 TI - Interpreting political agendas from a critical social theory perspective. PMID- 7885858 TI - The proposal-reality gap: the mechanics of implementing a funded research proposal. AB - In summary, planning is the key to smooth implementation of a newly funded study. Adequate planning reduces the time necessary to hire personnel, purchase equipment and supplies, acquire space, manage the budget, maintain agency contacts and provide for smooth agency orientation, and complete the pilot study. Moving smoothly into data collection ensures that the project will be on target by the end of the first year of funding and that the investigator will have an opportunity to demonstrate scholarly productivity. Pilot testing pieces of the research protocol during the period between submission of the proposal and notification of the funding decision will facilitate smooth transition either to data collection or to revision and improvement of the proposal for resubmission. PMID- 7885859 TI - Learning nursing process: a group project. AB - The group care plan strategy worked well with a mother and child as clients for a "child" course. It could be used with a pregnant client in a class on childbearing, or with an adult or geriatric person in other classes. Recent graduates of the program or retired or unemployed nurses might serve as models. Because of shrinking resources in nursing education today, efficient and effective strategies that meet learning needs of students and time constraints of faculty are essential. New ways of thinking about teaching are exciting and help to meet educational needs in today's fast-paced environment. PMID- 7885861 TI - Professional development. Anaemia: the role of the nurse. Part 2 (Continuing education credit). PMID- 7885860 TI - Standardizing the language for nursing treatments: an overview of the issues. PMID- 7885862 TI - Still mixed up. PMID- 7885863 TI - Signs of the times. PMID- 7885864 TI - On duty. Interview by Jane Cassidy. PMID- 7885865 TI - Last post. Interview by Jane Cassidy. PMID- 7885866 TI - End-stage renal failure: the challenge to the nurse. AB - End-stage renal failure is treatable but not curable. Clients' options are long term therapies or transplantation. This paper focuses on nurse-led, self-care treatment programmes with ESRF. The value and scope of such programmes is discussed and the role of the nurse explored. PMID- 7885867 TI - Renal failure. Symptom relief in ESRF. AB - This paper discusses the nursing care of a 65-year-old woman admitted to hospital with end-stage renal failure caused by the long-term effects of diabetes. Plans for the patient's discharge are also discussed. PMID- 7885868 TI - Developing local projects in primary health care in Wales. AB - The Edwards' report, a review of community nursing in Wales, offered significant pointers to enhancing the contribution of nurses in the community. In this article, the author describes how nurses in Wales, together with other primary health-care team members, responded to the challenge and achieved good results. PMID- 7885869 TI - Providing occupational health care in Northern Ireland. AB - In all areas of nursing, the concept of caring encompasses the core of our practice and is the outcome of skilled practitioners. In occupational health nursing (OHN) it is no different. 'Caring' has been described by many authors, used in theoretical models of nursing and forms the basis of much research. This paper looks at the provision of care in the OH setting within Northern Ireland, with particular reference to problems which have arisen from the troubles. PMID- 7885870 TI - Systems of life. The lymphatic system:2. PMID- 7885871 TI - Women's health. Screening for a solution. PMID- 7885873 TI - Working abroad. Cleared for take-off. Interview by Vittoria D'Alessio. PMID- 7885872 TI - Teaching the gentle way to labour. PMID- 7885874 TI - Pain control: TENS machines. PMID- 7885875 TI - Creative tension. PMID- 7885876 TI - Mental health. Look back at anger. PMID- 7885877 TI - Mental health. Handle with care. PMID- 7885878 TI - Professional development. Anaemia: revision notes (continuing education credit). PMID- 7885880 TI - A matter of chance. PMID- 7885879 TI - HIV infection among prison inmates. PMID- 7885881 TI - Out of sight. PMID- 7885882 TI - I'm Barbarella, fly me. PMID- 7885883 TI - Life-saving chore. PMID- 7885884 TI - Twelve-hour shifts: helpful or hazardous to patients? AB - This paper explores nursing shift patterns in the light of certain recently published reports and in particular the introduction and use of the 12-hour shift. It includes the personal observations of one nurse who recently changed to 12-hour shifts. Several central questions are raised and need to be answered before moves towards changes in staff deployment should be entertained. PMID- 7885885 TI - Nursing shifts. Is flexible rostering helpful? AB - Shiftwork is an essential part of nursing, where care is delivered over 24-hour periods. It is recognised, however, that such systems can have adverse physical and psychological effects on the people who have to work within them. This paper describes research into the value of flexible rostering and concludes that individual involvement in the timing and sequencing of shifts can reduce some of the problems normally encountered. PMID- 7885886 TI - NVQs as part of the pre-registration diploma. AB - National Vocational Qualifications (NVQs) seem to have taken hold of the popular imagination as somehow being more relevant to practical work than many other forms of nurse education. At one time NVQs were seen as having very low status, however, with the opening up of levels 3 and above, the practical benefits of professionals being able to demonstrate competence have started to gain not only popular, but also academic recognition. This paper demonstrates how one college of nursing has made a formal link between the NVQ scheme and higher education by preparing its Project 2000 students to be able to achieve a diploma of higher education and a respected National Vocational Qualification. PMID- 7885887 TI - The effects of cancer on body image and sexuality. AB - A diagnosis of cancer immediately threatens body image. Radiotherapy, chemotherapy and surgery can alter considerably a person's body image. This can have serious effects on the sexuality of cancer patients but these effects, for reasons to be discussed, are frequently dismissed by health professionals. It is argued that if they ignore their patients' sexuality, nurses are failing to deliver holistic care. This paper discusses the key effects of radical treatment on body image and the role nurses may play as counsellors. PMID- 7885888 TI - Full blood count (RBC, Hb, PCV, MCV, MCH and reticulocytes). AB - The full blood count (FBC) is a routine examination comprising a number of tests. This paper looks at those concerned with erythrocyte function, giving normal ranges and discussing some of the implications of abnormal results. PMID- 7885889 TI - Cross-cultural nursing. Culture clash. PMID- 7885890 TI - The way it was. PMID- 7885891 TI - International perspectives. A central theme. PMID- 7885892 TI - Labour of love. PMID- 7885894 TI - Human beans. PMID- 7885893 TI - Violence. Risky business. PMID- 7885895 TI - Continence. Hot lines. PMID- 7885896 TI - Continence. Must do better. PMID- 7885897 TI - A hard bargain. PMID- 7885899 TI - The backlash. PMID- 7885898 TI - Letter from Australia. PMID- 7885900 TI - Rules of attraction. PMID- 7885901 TI - Next-to-last resort. PMID- 7885902 TI - Old hopes. PMID- 7885903 TI - Careless talk. PMID- 7885904 TI - Psychological and emotional impact of an HIV diagnosis. AB - This is the first of two papers that reports the results of a research study into the psychological and emotional needs of people with HIV and how nurses might best offer support. This paper discusses the psychological impact of HIV diagnosis. Inductive analysis of indepth interviews with in-patients and their nurses generated five themes: reactions to critical events related to HIV infection; changes in body image and chronic ill health; fear and rejection; cognitive and minor dysfunction associated with HIV; and absent friends. PMID- 7885905 TI - Treatment options for managing diabetes mellitus. AB - When dietary restrictions alone fail to control diabetes, treatment is with oral hypoglycaemic agents or insulin. It is the nurse's role to help the client choose an appropriate form of treatment, and to teach him or her to monitor the effectiveness of his or her treatment. Nurses also have the responsibility of ensuring that clients understand how to prevent and treat hypoglycaemia. PMID- 7885906 TI - Providing for the needs of a dependent patient at home. AB - This article describes the complex nursing and social needs of a patient and her carer which were addressed before discharge home from units for the care of older people. It demonstrates how community care can work given effective planning coordination, collaboration and carer support. PMID- 7885907 TI - Asian women's attitudes to breast self-examination. AB - This pilot study investigates the attitudes of Asian women towards breast self examination and breast awareness. It attempts to identify why Asian women may not be aware of breast cancer or practise breast self-examination and discusses issues such as religious beliefs, psychological attributes, perception of the causes of breast cancer and the availability of resources and translated material. PMID- 7885908 TI - Improving communication in imaging departments. AB - Patient anxiety is often increased by poor communication from health-care staff. This paper describes an initiative in a radiology department to improve patients' knowledge of the nature of any investigations, before and during attendance at the department, using a combination of written and verbal explanations. PMID- 7885909 TI - The last battle. PMID- 7885910 TI - Bathing aids: handling and lifting in the home. PMID- 7885911 TI - Body politic: Mad Hatter's logic. PMID- 7885912 TI - Alternative update. PMID- 7885913 TI - Midwives' Journal. The benefits of team spirit. PMID- 7885914 TI - Midwives' Journal. A stitch in time. PMID- 7885915 TI - Midwives' Journal. Maternal HIV transmission. PMID- 7885916 TI - Use of total quality management sparks staff nurse participation in continuous quality improvement. AB - To improve patient care outcomes and reduce costs, hospitals are implementing the total quality management (TQM) model that has been successful in other industries. The Division of Nursing at one major medical center has devised a continuous quality improvement plan that incorporates TQM philosophy and methodology. This article describes how the TQM philosophy has evolved as the foundation for quality management at this medical center. PMID- 7885917 TI - Continuous quality improvement for peritoneal dialysis patients. AB - In addition to a significant savings in time, several qualitative factors were impacted positively by this change in practice. Clear guidelines provided a structure that both physicians and nursing supported, thereby improving their relationship. The LPN's role was amended to include the stop-and-start procedure, which enhanced their self-esteem. Having the assistive personnel contribute to the dialysis regimen allowed the RN more latitude in managing patient care and efficient use of time. Because the procedure was now done more efficiently, therapy was initiated without delay. Lastly, patients expressed satisfaction because the nursing staff's own technique and the patient was now being discharged without their own technique and the patient was now being discharged without delay. All RN and LPN staff continue to be trained in the procedure. Cases of peritonitis continue to be investigated with favorable results. Results of this project were shared not only with the staff but also with the management committee of the hospital. Management had embraced the philosophy of continuous QI. The management committee was anxious to see the principles of continuous QI improve efficiency and patient outcomes. Reducing the complexity and decreasing the time required for the procedure maintained quality patient outcomes. Applying the continuous quality monitoring process and tools to the management of one group of chronically ill patients was shown to be an effective means of improving patient care and efficiency as well as of reducing costs. PMID- 7885918 TI - It all comes down to degrees. The QI process between two units. AB - Cold stress is potentially life-threatening to a 600-g neonate. The risk of cold stress is increased during the admission process, when a neonate is transferred from a labor and delivery suite to a patient care unit. At one perinatal center, staff nurses devised a quality improvement plan to assess and reduce the risk of cold stress to patients admitted to the neonatal intensive care unit. PMID- 7885919 TI - Protecting the provider from tuberculosis exposure. AB - The resurgence of tuberculosis (TB), especially the new multi-drug-resistant strain of TB, is a potential health hazard for caregivers in hospital settings. This article discusses the comprehensive multidisciplinary evaluation of one medical center's policies and procedures related to the control of infectious airborne pathogens. PMID- 7885920 TI - Where does it hurt? An interdisciplinary approach to improving the quality of pain assessment and management in the neonatal intensive care unit. AB - Identifying a premature infant's response to noxious stimuli and knowing when it is appropriate to intervene are major issues for the caregiver. After completing a pilot study, the staff of a 42-bed neonatal intensive care unit targeted improved pain assessment and management for further analysis. Using a series of Plan, Do, Check, and Act cycles they designed a stepwise set of interventions that resulted in the improved assessment and management of the neonate in pain. PMID- 7885921 TI - Improving quality of patient care services for outpatient observation patients. AB - This article focuses on the history of observation status, the principles of observation bed usage, and the issues related to observation patients' processing at RPSLMC. The role of the interdisciplinary team in designing a patient-centered and revenue-capturing quality operation is described. Several quality indicators are currently monitoring the effectiveness and efficiency of the observation system. PMID- 7885922 TI - Improving the admission process from the emergency department to the critical care areas. AB - The CCU and CSU successfully established an interdisciplinary QI team. Through the implementation of the QI process the group focused on an indicator that influenced patient satisfaction. QI tools were effectively used to analyze the complex admission process of CCU and CSU patients admitted through the ED. Quality tools were also used to analyze the data over time. The QI process and methodology were effectively implemented to address a complex problem. The results will serve as a foundation for the new process improvement committee focusing on the unstable angina population. PMID- 7885923 TI - Reducing central line catheter infections in bone marrow transplant patients. AB - Infection can be detrimental in any patient, but it is life-threatening in the immunocompromised BMT patient. It was the nursing staff that first identified an increased rate of central line infections. Placing the CVC just prior to the conditioning regimen, on admission for BMT, as opposed to a 23-hour same-day admission, decreased infection rates significantly, from 50% to 16%. The final goal of a 0% infection rate, however, was not obtained without thorough patient education and consistent documentation of catheter care by the nursing staff. This study clearly supports the crucial role nurses have in decreasing infection rate in this patient population. As a result, it is possible to decrease the length of stay, decrease hospital costs, and ultimately decrease patient mortality rates. PMID- 7885924 TI - Expansion of the seizure monitoring program. A collaborative approach. AB - This article discusses an interdisciplinary total quality management (TQM) project that planned for the expansion of the seizure monitoring program on a neuroscience unit. The processes of education, bed management, and patient care were evaluated by a TQM group of staff nurses, unit leader, attending physicians, clinical nurse specialist, and technicians. Each participant identified actual and potential problems and their effects on the participant's area of care. PMID- 7885925 TI - Needlestick injuries. A multidisciplinary concern. AB - This article outlines a variety of steps implemented by the medical center in an effort to reduce the number of needlestick injuries among nurses within our institution. Overall, we have seen a decline in needlestick injuries with the greatest decline among the nursing staff. We attribute this decline to staff education, improved needle-disposal containers, and the addition of needleless products for IV infusions. More important, a rigorous quality-management approach, including employee involvement, the sharing of data throughout the institution, and management commitment to the issue, has enabled continuous improvement. We are in the process of refining our methods so that future decisions regarding neddlestick injury reduction-activities will more specifically address problem areas. PMID- 7885926 TI - The medical-psychiatric consultation liaison nurse. Meeting psychosocial needs of medical patients in the acute care setting. AB - This article focuses on the development of the role of the MPCLN in the acute care setting. The need for such a role clearly exists to meet the complex needs of medical inpatient populations. Patients with primary psychiatric disorders or psychiatric disorders concomitant or secondary to physical disease, as well as the growing elderly population will all require psychiatric interventions. Less than 1% of acute care medical patients receive psychiatric care for psychiatric symptoms and disorders. Implementing the role of the MPCLN would have a positive impact on quality of care, reduced health care costs, decreased patient LOS, and nursing satisfaction. PMID- 7885927 TI - Contracted visiting hours in the coronary care unit. A patient-centered quality improvement project. AB - As critical care technology advances, the need to provide patient-centered care becomes increasingly critical. Grandstrom states that patients and families want "more." They have greater expectations and demand greater knowledge and involvement, vis-a-vis the hospital experience. Rather than indicating a desire to observe procedures or equipment, these expectations reveal a more personal and human need--the desire of patients and families to maintain contact and interact with one another. Allowing patients and families control over visiting times in a critical care setting is the first step in giving families and patients what they need. The use of contracted visiting hours allows families and patients to maintain some control over their lifestyles during a crisis. This project is still in progress. The evolution of the perfect contract continues. The outcome of increased flexibility and control of visiting times for families has been embraced and supported by the staff. It is believed that implementation of flexible visiting hours has increased the staff's awareness of the patient and family as consumers. In today's competitive health care environment, Artinian proposes that "strengthening relationships with families may make the critical difference related to patients' and families' choices about whether a health-care setting meets their needs." By implementing flexible visiting hours these relationships are enhanced and consumer satisfaction is influenced. Also, the institutional goal of patient-centered care, and ultimately quality patient care, is promoted. PMID- 7885928 TI - Renovation of a semiprivate patient room. Bowman Center Geriatric Rehabilitation Unit. AB - A multidisciplinary total quality management (TQM) environment committee was formed to create a more accessible, home-like environment for patients on a geriatric rehabilitation unit. Problems in semiprivate rooms related to wheelchair use and age-related changes in the elderly were identified. After using the TQM process to find solutions to these problems, the committee remodeled two semiprivate rooms. Surveys indicate improvement in accessibility, storage, lighting, appearance, and cleanliness. PMID- 7885929 TI - Clinical usefulness of rate adaptive pacing systems: what should we assess? PMID- 7885930 TI - Rate adaptive cardiac pacing using right ventricular venous oxygen saturation: quantification of chronotropic behavior during daily activities and maximal exercise. AB - Central venous oxygen saturation (SvO2) closely reflects cardiac output and tissue oxygen consumption. In the absence of an adequate chronotropic response during exercise, SvO2 will decrease and the extent of desaturation may be used as a parameter for rate adaptive cardiac pacing. Eight patients with sinoatrial disease received a DDDR pacemaker capable of DDDR pacing by sensing either SvO2 or piezoelectric detected body movement. Both sensors were programmed to attain a rate of about 100 beats/min during walking, and with the lower and upper rates set at 50% and 90% of age predicted maximum, respectively. Chronotropic behavior of the two sensors were compared in the DDD mode with measurement of sensor responses, during everyday activities (walking, stair climbing, postural changes, and physiological stresses) and at each quartile of workload during a continuous treadmill exercise test. During walking at 2.5 mph, both sensors showed no significant difference in delay time (both react within 15 secs) or half-time (SvO2 = 36 +/- 12 sec and activity 24 +/- 3 sec; P = NS), although SvO2 driven pacing achieved 90% target rate response slower than activity sensing (124 +/- 16 sec vs 77 +/- 10 sec; P < 0.02). SvO2 pacing was associated with a more physiological rate response during walking upslope (68 +/- 12 beats/min vs 57 +/- 10 beats/min; P < 0.05), ascending stairs (59 +/- 10 beats/min vs 31 +/- 6 beats/min; P < 0.05), and standing (34 +/- 7 beats/min vs 9 +/- 2 beats/min; P < 0.05). The SvO2 sensor significantly overpaced in the first quartile of exercise (51.8 +/- 25.6% in excess of heart rate expected from workload), but the rate was within 20% of expected for the remainder of exercise. "Underpacing" was observed with the activity sensor at the higher workload. In conclusion, the SvO2 sensor demonstrated a more physiological response to activities of daily living compared with the activity sensor. Using a quantitative method, the speed of onset of rate response of the SvO2 sensor was comparable to activity sensing, and was more proportional in rate response. Significant overpacing occurs at the beginning of exercise during SvO2 driven pacing, which may be improved with the use of a curvilinear algorithm. PMID- 7885931 TI - Implantation of an automatic defibrillator using a new nonthoracotomy approach. AB - Most current nonthoracotomy systems for defibrillator implantation use monophasic devices. To determine the safety and efficacy of a new nonthoracotomy lead configuration when used in conjunction with a device that used biphasic waveforms, 38 consecutive patients were taken to the operating room for implantation of a Cadence tiered therapy defibrillator system. The lead system consisted of a transvenous coil electrode positioned at the right atrial-superior vena caval junction, a bipolar endocardial right ventricular lead, and a large patch placed subcutaneously near the cardiac apex. Of the 38 nonthoracotomy defibrillator implantations attempted, 36 (95%) were completed with adequate defibrillation thresholds. The mean defibrillation threshold in these 36 patients was < or = 563 +/- 10 V (< or = 20 +/- 1 J). There was no perioperative mortality. Complications included coil lead migration (5), sensing lead migration (1), infection (3), pneumothorax (2), arterial embolism (1), and folding of the subcutaneous patch with an increase in defibrillation threshold (1). No patient died during a median follow-up period of 22 weeks. Fourteen patients (39%) had spontaneous sustained ventricular tachyarrhythmias, which were all successfully terminated by the implanted device. Shocks for nonsustained arrhythmias were aborted in eight patients (22%). Spurious discharges for sinus tachycardia or atrial fibrillation occurred in six patients (17%) and were readily diagnosed by examination of the stored electrograms. Thus, implantation of a biphasic tiered therapy defibrillator system using this nonthoracotomy approach is feasible in the majority of patients. The major complication associated with this procedure is lead dislodgment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885932 TI - Heart weight affects spontaneous defibrillation but not ventricular fibrillation threshold. AB - Among the factors involved in the induction, generalization, and reversion of cardiac fibrillation, the amount of tissue is a determinant factor. One question is whether an increase in myocardial mass would or would not require the same electrical threshold. Accordingly, one objective was to determine if ventricular weight (VW) has any effect on the fibrillation thresholds (FTs). A second objective was to find a possible relationship between spontaneous defibrillation (SPDE) and heart weight. Fifty mongrel dogs of both sexes were used, of which 26 were 2- to 10-week-old puppies. The rest were adult animals of undetermined age. Fibrillation was induced with two types of stimuli directly applied to the heart. The stimuli were a train of rectangular pulses (TP) not synchronized with the ECG, and single pulses (SP) synchronized with and delayed from the R wave. TP type was used in one group with paddle electrodes; and the TP and SP types were used in a second group with hook electrodes. For both types, stimulation started at a low current and was increased until fibrillation was triggered. Once defibrillated, either spontaneously or by electrical shock, the procedure was repeated. Correlation coefficients between FT and VW were low (< 0.4), and scaling of the thresholds to VW resulted in hyperbolic relationship, for all cases, thus suggesting independence of the two parameters. SPDE fell sharply with weight. For values higher than 12 grams it was essentially nonexistent. VW does not have any effect on the FT but it dramatically influences the capacity of the myocardium to revert the arrhythmia by itself. PMID- 7885933 TI - Safety and diagnostic yield of noninvasive ventricular stimulation performed via tiered therapy implantable defibrillators. AB - Extensive electrophysiological testing is critical for the effective utilization of sophisticated tachycardia detection and termination algorithms available in tiered therapy ICDs. To evaluate the safety and diagnostic yield of electrophysiological testing via noninvasive ventricular stimulation, we performed 294 electrophysiological studies in 154 patients (age 65 +/- 10; left ventricular ejection fraction 0.36 +/- 0.15) with tiered therapy ICDs. Stimulation was performed under methohexital anesthesia. A total of 918 sustained ventricular tachyarrhythmias were induced (3.1 +/- 2.5 per procedure): monomorphic VT, 550; ventricular flutter, 74; and VF, 246. The results of invasive and noninvasive programmed stimulation were compared for 79 patients who had both studies under similar treatment. Overall concordance was 83%, and did not differ significantly between patients who had the noninvasive stimulation via epicardial or endocardial pacing leads. VF could be induced in 206 of 257 studies (82%), and it was less likely to be induced in patients on amiodarone (74% vs 85%; P = 0.02), or beta blockers (55% vs 83%; P = 0.017). No patient presented a serious complication. Minor complications occurred during 39 studies: transient laryngospasm in 1, unintended delivery of an ICD shock to a conscious patient in 4; induction of sustained atrial fibrillation in 8; need for external rescue defibrillation shocks in 13; and delivery of inappropriate shocks for supraventricular rhythms in 14 studies. Noninvasive ventricular stimulation performed under methohexital anesthesia is safe. Its diagnostic yield compares favorably with that of conventional electrophysiological studies. VF can be induced in a majority of patients. There is good correlation between invasive and noninvasive programmed stimulation for induction of VT. Noninvasive ventricular stimulation may emerge as standard procedure for the initial programming and follow-up of ICDs. PMID- 7885934 TI - The usefulness of a stretch-polyester pouch to encase implanted pacemakers and defibrillators. AB - This study was undertaken to assess the effects of enclosing permanent pacemaker and ICD pulse generators in a stretch-polyester pouch prior to implantation. Follow-up of 223 patients with oversized pacemakers and with ICDs and 344 with standard-sized pacemaker pulse generators showed that the pouch was effective in decreasing the frequency of pulse generator migration and extrusion. PMID- 7885935 TI - Mexiletine has no effect on defibrillation energy requirements in dogs. AB - Many of the antiarrhythmic drugs produce a rise in the ventricular defibrillation threshold (DFT). Although mexiletine has also been reported as the probable cause of a significant elevation of DFT, there has been no previous study; therefore, the effect of mexiletine on DFT was investigated in the present study. The experiments were performed on ten mongrel dogs in the open-chest state using general anesthesia. Mexiletine 1, 2, 4, 6, or 8 mg/kg was administered as the loading dose, followed by the same dose/kg per hour. In these five groups, fibrillation/defibrillation (F/D) trials were performed repeatedly every 10 minutes, until 60 minutes after starting the maintenance dose. F/D trials were also performed at 30, 45, and 60 minutes after the completion of mexiletine infusion. The heart was allowed to fibrillate for a total of 30 seconds. Applying internal paddles to the heart, energies of 2, 3, 5, 7, 10, 20, and 30 J maximum were used. The minimal energy shock that caused defibrillation was defined as the DFT. The mexiletine concentration in each group changed from 0 to 6.11 micrograms/mL, DFT ranged from 2-10 J, and no statistical correlation was found between mexiletine concentration and DFT. We conclude that mexiletine does not induce an increase in DFT in dogs. PMID- 7885936 TI - Safety of pacemaker implantation in patients with transvenous (nonthoracotomy) implantable cardioverter defibrillators. AB - While several reports have documented the safety of implantation of transvenous pacemakers in patients with epicardial patch-based implantable cardioverter defibrillators (ICDs), the implantation of transvenous pacemakers in patients with transvenous (nonthoracotomy) ICDs has not been well-described. We present three patients with transvenous ICDs who subsequently underwent implantation of transvenous pacemakers without complication. Technical considerations and a testing, protocol for detection of pacemaker-ICD interactions are discussed. PMID- 7885937 TI - Unsatisfying results in long-term atrial pacing with a bipolar active fixation atrial lead. AB - A high dislodgment rate during long-term atrial pacing using the unipolar sickle shaped active fixation lead was recently reported; therefore, the long-term results of atrial pacing in 118 consecutive patients with the bipolar sickle shaped active fixation lead (Biotronik FH60-BP) were evaluated. Between January 1989 and September 1993, 87 leads (74%) were inserted for dual chamber pacing and 31 leads (26%) for atrial pacing only. At the time of implantation, the bipolar atrial electrogram had a mean voltage of 4.4 +/- 1.6 mV, whereas the acute atrial threshold was 0.72 +/- 0.38 V and 1.46 +/- 0.67 mA at 0.5-msec pulse duration and mean resistance 506 +/- 79 omega. Early lead dislodgment (< 1 month after implantation) occurred in 9 patients (7.6%). During a mean follow-up of 21.8 months (median 20.9 months), late dislodgment (> 1 month after implantation) occurred in 6 patients (5.1%) after a mean interval of 7.9 months (range 3-14 months). Due to the unacceptably high late dislodgment rate, which to date remains unexplained, new implants of this lead are not recommended. PMID- 7885938 TI - The economic impact of transvenous defibrillation lead systems. AB - The purpose of this study was to compare implant charges and convalescence for transvenous and epicardial defibrillation systems. Hospital stay, intensive care utilization, professional fees, and hospital bills were compared in 44 patients who underwent implantation of a cardiac defibrillator between September 1991 and May 1993. Twenty-five consecutive patients received an epicardial lead system, while 19 consecutive patients underwent implantation of the entire transvenous defibrillation system in the electrophysiology laboratory. There were no significant differences between the two groups in mean age or left ventricular ejection fraction. There was a significant reduction in postoperative hospital convalescence from 7.2 +/- 2.0 days with epicardial systems to 3.1 +/- 1.5 days with transvenous systems (P < 0.001). Postoperative intensive care unit stay was significantly reduced with transvenous systems compared with epicardial systems (0.1 +/- 0.2 vs 1.5 +/- 0.9 days; P < 0.001). Hospital charges were also significantly reduced with the transvenous lead system implants. Mean implant charges were lower with transvenous systems: $32,090 +/- $2,620 vs $38,307 +/- $2,701 (P < 0.001); convalescence charges were lower: $5,861 +/- $5,010 $12,447 +/- $4,969 (P < 0.001); the total hospital bill was also significantly lower with transvenous systems: $53,459 +/- $12,588 vs $71,981 +/- $16,172 (P < 0.001). Professional fees for implantation ($4,131 +/- $1,724 vs $6,100 +/- 0, P < 0.001), convalescence care ($1,258 +/- $960 vs $2,846 +/- $1,770; P < 0.001), and total professional fees ($12,925 +/- $4,772 vs $15,731 +/- $4,055, P < 0.05) were lower in the transvenous defibrillation group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885939 TI - Ventriculoatrial conduction in patients with implantable cardioverter defibrillators: implications for tachycardia discrimination by dual chamber sensing. AB - Incorporation of atrial electrograms in the tachycardia detection algorithm may improve tachyarrhythmia discrimination by ICDs but retrograde ventriculoatrial (VA) conduction over the AV node during ventricular tachyarrhythmia may be problematic. The present study analyzed VA conduction characteristics in 66 ICD patients who had evaluation of the VA conduction system by electrophysiological studies before implant. VA conduction was demonstrated in patients during ventricular decremental stimulation. Forty patients had inducible sustained monomorphic VT. The minimum cycle length maintaining 1:1 VA conduction during ventricular stimulation was longer than the cycle of VT in every patient (496 +/- 100 msec vs 320 +/- 81 msec; P < 0.01). Occasional VA conduction during VT was observed in five patients and one patient had 2:1 VA conduction during induced VT. No patient had 1:1 VA conduction during VT. We conclude that brisk VA conduction is uncommon and 1:1 VA conduction during VT is rare ICD recipients. VA conduction is unlikely to complicate the incorporation of atrial electrograms into tachyarrhythmia detection algorithms. PMID- 7885940 TI - Effect of chronotropic response pattern on oxygen kinetics. AB - BACKGROUND: The sinus node is considered to be the model of chronotropic response for pacemakers that use artificial rate modulating sensors. Maximal metabolic exercise testing with measurement of oxygen consumption (VO2) is frequently used to evaluate chronotropic response. Since activities of daily living are generally transient and involve submaximal effort, maximal exercise testing may not provide the most clinically relevant method of assessing rate modulation. The purpose of this study was to determine if an abrupt increase in heart rate (HR) at the onset of submaximal exercise provides improved oxygen kinetics compared with a linear response. METHODS AND RESULTS: Thirteen patients with complete heart block and permanent rate modulating pacemakers implanted following catheter ablation of the atrioventricular junction for refractory atrial fibrillation were chosen for study. The patients first completed a maximal treadmill exercise test using the chronotropic assessment exercise protocol with breath-by-breath analysis of expired gases. The expected HR at 50% of metabolic reserve was calculated for each patient. Three submaximal constant workload exercise tests were then performed at 50% of each patient's metabolic reserve, with the pacemaker randomly programmed to provide three different patterns of chronotropic response: linear (in which HR increased from 70 beats/min to the expected HR at 50% of metabolic reserve), fast (in which HR was abruptly increased to the expected HR at 50% of metabolic reserve), and slow (VVI at 70 beats/min). Oxygen kinetics were compared for the three patterns of chronotropic response. Cumulative oxygen (O2) consumption was significantly greater for the fast pattern (3610 mL) as compared with the linear (3487 mL, P = 0.004) or slow pattern (3277 mL). The O2 deficit was lower for the fast (361 +/- 139 mL) than for the linear (539 +/- 225 mL, P = 0.003) or slow chronotropic pattern (559 +/- 194). Similar improvements in the rate constant of O2 uptake and Borg perceived exertion scores were observed with the fast chronotropic response pattern. CONCLUSION: A rapid increase in pacing rate at the onset of exercise improves oxygen kinetics and results in less perceived exertion as compared to a more gradual rate increase that is more characteristic of sinus node behavior. PMID- 7885942 TI - Complexity diagnostics in cardiology: methods. PMID- 7885941 TI - Why is catheter ablation less successful than surgery for treating ventricular tachycardia that results from coronary artery disease? AB - Nearly 80% of patients with coronary artery disease who have map-directed surgery for control of ventricular tachycardias require no drug therapy to prevent recurrences, while fewer than 50% of patients undergoing catheter ablation have similar outcomes. Catheter ablation will fail if arrhythmogenic sites are incompletely ablated by lesions that are too small or too far away from the reentrant pathway or if all arrhythmogenic sites are not identified. The underlying assumptions used to guide site selection are that: (a) ventricular tachycardias arise from reentrant mechanisms; (b) monomorphic ventricular tachycardias with similar QRS morphologies arise from the same pathway; (c) the ventricular tachycardia initiated during the procedure represents the patient's spontaneous arrhythmia; (d) the endocardial site that should be ablated can be identified from cardiac activation maps produced during induced ventricular tachycardia or from ancillary techniques; and (e) the patient has only one or two reentrant pathways. Relying on incorrect assumptions may account for the difference in success rates. Patients may have similar appearing ventricular tachycardias that arise from different pathways, and the entire thin layer of viable tissue between the infarct and the endocardium may contain many reentrant pathways. Some ventricular tachycardias may arise from the myocardium away from the endocardium, while others may arise from the epicardium. Small lesions may not be large enough to eliminate all possible reentrant pathways. Catheter ablation may be less successful because the lesions are inadequate, the assumptions guiding the selection of arrhythmogenic tissue are incorrect, or all arrhythmogenic sites are not identified. The primary reason catheter ablation is less successful than surgery in the treatment of ventricular tachycardias is that catheter ablation does not ablate as much tissue as is removed by surgery. The success rate of catheter ablation probably can be improved if the amount of tissue ablated is increased. PMID- 7885943 TI - Clinical research, federal regulations, and payment policy: a case study for health regulation reform. PMID- 7885944 TI - Percutaneous removal of infected permanent pacemaker leads using a simple coaxial dilating system. AB - A simple traction-countertraction technique using common and readily available materials was successfully used to remove infected pacemaker leads from two patients. The specific methodology is presented. Although somewhat technically demanding, this approach appears safe and cost-effective. This method provides another way to remove pacemaker leads without resorting to thoracotomy. PMID- 7885945 TI - Inadvertent defibrillator sense/pace lead placement in the middle cardiac vein: a possible complication with new implications. PMID- 7885947 TI - STIMAREC report. PMID- 7885946 TI - Cerebral embolism due to left ventricular pacemaker lead: removal with cardiopulmonary bypass. AB - Malposition of a cardiac pacemaker lead within the left ventricle represents a source of early and late thromboembolic complications. We report a case of cerebral embolism, caused by an inadvertently misplaced left ventricular electrode, occurring 3 years after implantation. The lead was removed via a transaortic approach with extracorporeal circulation. PMID- 7885948 TI - [Allergy to cow's milk proteins in childhood: the authors' personal experience and new diagnostic and therapeutic proposals]. AB - Cow's milk protein is quite commune in infancy (2-3% in first year of age). Casein, beta-lactoglobulin and alpha-lactalbumin are the main allergens of cow's milk. The authors describe the immunological reaction involved in IgE synthesis and consequential inflammation after ingestion of cow's milk proteins and present soy and protein extensive hydrolysates as alternative diets for children with cow's milk allergy. Moreover, the authors present their studies on immunogenicity of hydrolysed formulae. At the end they suggest the therapeutic strategy in the cow's milk protein allergy. PMID- 7885949 TI - [The inhalational therapy of respiratory pathology]. AB - The inhalation of aerosolized drugs for therapeutic purpose has been used for many years in respiratory diseases as asthma, chronic bronchitis, cystic fibrosis. Therapeutic aerosols have the advantages to deliver active substances directly to the site of disease, without systemic side effects, to produce a more rapid clinical response, to avoid barriers to the absorption of drugs such as the gastrointestinal tract. We review the mechanisms and the site of lung deposition and the range of devices that can provide an effective aerosol such as metered dose-inhaler and spacers. Besides drugs as cromolyn, beta-2-agonists and topical steroids, recently new inhalation therapies were proposed using antiviral drugs (interferon), pentamidine for Pneumocystis carinii in immunocompromised host, inhalation of attenuated virus (measles) for active immunization. However there is a need for further work in this area. PMID- 7885950 TI - [The child with recurrent infections: a problem of pediatric practice]. AB - A wide range of topics can be included under the heading of recurrent infections in children. This discussion focuses on 1) the definition of recurrent infection and physiopathogenetic mechanisms predisposing to; 2) controversies in the management of upper respiratory tract infections; 3) recurrent upper and lower respiratory infections in immunocompromised hosts, emphasizing advances in diagnosis and treatment of "mild" immunodeficiencies such as IgG subclass deficiency or antibody deficiency in normogammaglobulimia, trying to define an operative flow chart. PMID- 7885951 TI - [Intraesophageal pH measurement in childhood: the technic and indications]. AB - This review evaluates methodologic problems concerning esophageal pH monitoring in pediatric patients. Prolonged intraesophageal pH recording (twenty-two or twenty-four hour) is considered as the gold standard for all reflux investigations. The indications to pH monitoring and the interpretation of long term pH studies data are discussed in details in the paper. PMID- 7885952 TI - [Gastroesophageal reflux and respiratory pathology: a study comparing radiology and intraesophageal pH measurement]. AB - From November 1st, 1992 to August 31st, 1993 45 children with respiratory symptoms of gastroesophageal reflux (GER) were tested with barium esophagogram and 24 h intraesophageal pH-monitoring to determine their sensitivity in detecting gastric acid reflux and to document their usefulness as a prognostic indicators. Results showed that thirty-seven of these patients had GER on esophagograms and that 24 h intraesophageal pH monitoring was positive in thirty nine patients. However, we found a high incidence of false-negative results of the upper gastrointestinal series when the pH monitoring was positive. PMID- 7885954 TI - [The prevention of congenital damage: the infectious aspects]. AB - During the intrauterine life or at birth, the product of conception is exposed to a lot of different and mostly still unknown risk factors among which the infective agents take on great importance owing to the proportion of the problem and to the fact that most of them can be avoided. Depending on the cases, for the baby welfare, measures of primary or secondary prevention are enforced; they are mainly based on serologic tests to the mother. After recalling the frequency and the effects of connatal injury of each infective pathology, the Authors examine the ways of infection of the coming or newborn baby according to the period of growth subsequently, the ways of avoiding the infection and the preventive treatments available or under study are examined. PMID- 7885953 TI - [Neonatal screening for cystic fibrosis]. AB - Cystic fibrosis (C.F.), a congenital lethal disease involving many organs, is responsible of chronic pulmonary disease and maldigestion. At the beginning symptoms can be feeble and diagnosis is often delayed, especially in those cases with an isolated pulmonary expression. It is demonstrated that early diagnosis and immediate prophylaxis of pulmonary infections and maldigestion improves survival. Thus a neonatal screening test is required. Although various attempts have been done, dating from 1968, there is no evidence, up to now, of a real utility of neonatal screening tests in C.F. The only test with a minor frequency of false negatives and positives is the RIA trypsin serum dosage to be executed within 3-5 days of life. PMID- 7885955 TI - [The milk bank and its organization in a large hospital complex]. PMID- 7885956 TI - [Celiac disease in children with Down's syndrome]. AB - The coexistence of Down's syndrome (DS) and coeliac disease (CD) has been occasionally reported and both diseases are often related to autoimmune disorders. The pathogenetic factor that links CD and DS may be an altered immune system and/or the presence of a common genetic factor. Some epidemiological investigations, performed in patients with CD, showed an increased incidence of DS compared to the natural incidence of this abnormality in the general population. We studied the prevalence of CD in 83 individuals with DS compared to a group of 200 patients with other gastroenterologic disorders and a random scholastic sample of 500 non symptomatic children. IgG and IgA antigliadin antibodies (AGA) were determined in all patients. Antiendomysium antibodies (EmA) were investigated in all the patients of the first group, while in the other two groups, 27 and 108 cases respectively, selected by AGA positivity, were investigated for EmA. The percentage of AGA IgA positivity in the first group was 31.3% (26/83), in gastroenterologic controls 10% (20/200), in scholastic sample 2.8% (14/500), that shows a significant statistical difference. On the contrary EmA were positive in quite a similar percentage in the three groups. Duodenal [correction of Jejunal] biopsies, were performed in 11 DS patients and in 9 of the other two groups. EmA were positive only in the case with subtotal atrophy in all the groups: 5/11 in the first, 2/4 in the second, 2/5 in the third. On the contrary AGA IgA were often positive also in patients with non coeliac histologic findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885957 TI - [Blood insulin values after the oral glucose tolerance test (OGTT) and the body composition in 30 obese children]. AB - The body composition and plasma insulin after OGTT were evaluated in 30 obese children, aged 6 to 14 years. The obese children higher serum insulin after OGTT. There was a relationship between plasma insulin and Body Mass Index (MBI) and between plasma insulin and Weight For Height (WFH) (p < 0.001). There is the accumulating evidence that chronic day-long hyperinsulinemia is associated with an insulin-resistance syndrome characterized by the development of hypertension, hyperlipidemia, atherosclerosis and non insulin depend diabetes. PMID- 7885958 TI - [Anemia and hepatosplenomegaly: search for the protozoon?]. AB - An eight-months-old infant presenting with anemia, hepatosplenomegaly, hypoalbuminemia and polyclonal hypergammaglobulinemia was finally found to be affected by visceral leishmaniasis, after having suspected oncohaematologic problems. Diagnosis was confirmed by bone marrow aspiration. Complete recovery was achieved with antimonial N-methylglucamine (Glucantim) administered IM. PMID- 7885959 TI - [The use of the Gasthmatic System in studying bronchial hyperreactivity]. AB - The Gasthmatic System is a new method for monitoring transcutaneously pO2 and pCO2 changes prior to, during and after bronchial provocation. Unlike normals, asthmatic and atopic subjects reproduce the same gas patterns: immediate transient hypocapnia, during inhalation of ultrasonically nebulised distilled water (UNDW) (dead space effect) and delayed more persistent hypoxia, after end of UNDW exposure. This pattern is suggestive of an uneven distribution of the alveolar ventilation and ventilation/perfusion ratio and is noted both in asymptomatic asthmatics and in nonasthmatic atopic rhinitis subjects FEV1-non responders to UNDW. This distributional pattern, therefore, appears to be able to screen very early stages of airway disease, when conventional parameters of lung volumes and mechanics fail to reveal any significant changes in hyper-reactive response. The Gasthmatic model is simple, painless, effortless, and allows transcutaneous measurements during all the phases of the hyperreactivity test, including the actual stimulation phases. It proves, therefore, to be particularly useful for children too young to cooperate with common lung function tests. PMID- 7885960 TI - [The natural history of allergy to eggs in atopic dermatitis]. AB - The outcome of atopic dermatitis and the incidence [correction of prevalence] of asthma was ascertained in a four-year follow-up in 47 children with eczema due to egg allergy. At the end of the study, skin lesions had cleared in 32 (68%) children. Of these, 18 (38.2%) developed tolerance to egg about two years after diagnosis, while 14 (29.7%) continued an elimination diet. Fifteen children (31.9%) are still affected by eczema due to discontinuation of the egg-free diet. At the end of follow-up, 23 children had presented at least three asthma episodes. Therefore, the incidence [correction of prevalence] of asthma in children with atopic dermatitis appears to be significantly higher when egg allergy is present. Egg allergy could be a marker of an atopic condition and therefore be an unfavourable prognostic signal as to the outcome of the disease and the appearance of respiratory allergy. PMID- 7885961 TI - [Acute psychosis and vigabatrin in childhood]. AB - Vigabatrin is an irreversible inhibitor of gamma-aminobutyrate (Gaba) aminotransferase, producing an increase in Gaba concentrations in the brain. It may prove to be an important drug in the treatment of refractory epilepsy, but would be payed attention to behavioural changes noted in association with vigabatrin treatment. Behaviour disturbances, as psychosis, associated to vigabatrin are ben described in adult patients, while are uncommon in childhood. We report a case of acute psychosis occurred in a child in treatment with vigabatrin. PMID- 7885962 TI - [The new parents. The importance of the pediatrician-child-parent triad]. AB - During these past years pediatricians have been more and more interested to the adolescent's matters. Undoubtedly adolescent's behavioural disturbances are to be bound to a childhood spent in a wrong way, and contemporarily managed by parents who, despite their maximum dedication, have not "trained" their children according to specific "fundamentals", probably because also they themselves, when children, have not been submitted to them. PMID- 7885963 TI - [Ovarian cysts in the differential diagnosis of acute and recurrent abdominal pains]. AB - The authors review the differential diagnosis in the acute and recurrent abdominal pain and the classification of ovarian cysts in prepuberal girls. They report the description of three cases of ovarian cysts in prepuberal girls and the role of ultrasonography in their diagnosis in a paediatric department. PMID- 7885964 TI - [The surgical treatment of fixed aortic subvalvular stenosis]. AB - Over the past 5 years, 45 patients (11 adults and 33 children) have undergone operations for discrete and fixed subaortic stenosis. The resection of the subvalvular membrane or the fibromuscular collar was the procedure of choice. 28 patients underwent myectomy and/or myotomy. None patients died during operations. No significant symptoms and gradients remained after operation. We conclude that in the surgical management of fixed discrete subaortic stenosis myectomy and myotomy in addition to membranectomy produces better relief of the left ventricular outflow obstruction than do membranectomy alone. PMID- 7885965 TI - [The laparoscopic treatment of Hirschsprung's disease]. AB - Swenson's procedure, first described in 1948 for Hirschsprung's disease, consists in resection of aganglionic intestine and distal colo-anal anastomosis provided a precise dissection of extra peritoneal rectum. Potential jeopardy of pelvic vessels and nerves stimulated alternative surgical techniques to prevent complications on bladder and genital function. We performed in laparoscopy Swenson's procedure after Toupet, taking advantage from closer view and magnification of this technique, in a 15 months girl. Laparoscopy simplified and made safer pelvic dissection and resulted in a better postoperative period and cosmetic outcome. PMID- 7885967 TI - Recombinant interleukin-2. AB - Recombinant interleukin (IL)-2 is a newly approved immunoregulatory protein produced by lymphocytes that exhibits a wide range of immunologic effects. It is a true biologic response modifier in that is has no known direct antitumor activity, but mediates its cytotoxicity through activation of effector cells including T cells, natural killer cells, and lymphokine-activated killer cells. Recombinant IL-2 has demonstrated activity in patients with renal cell carcinoma and melanoma, with objective response rates of approximately 15-20%. The median duration of response in renal cell carcinoma is 23 months. Toxicity experienced with high-dose IL-2 can be significant. The most common dose-limiting toxicities are hypertension, weight gain, oliguria, respiratory insufficiency, and neurotoxicity. These effects are generally manageable and reversible on discontinuation of therapy. Administration of low-dose IL-2 has emerged as a means of substantially reducing toxicity. At least in renal cell carcinoma, it appears that the response rate to low-dose IL-2 is comparable to that with higher dosages. PMID- 7885966 TI - [The herniated disk in childhood: a case report and review of the literature]. AB - A 12-years-old female subject, without previous history of trauma, complained of mild low-back pain and right sciatic pain. At physical examination the ankle jerk was absent on the right and severe leg pain was elicited by the Lasegue test. No sensory or motor deficits were detectable. Computed tomography and nuclear magnetic resonance examinations showed a right paramedian L5/S1 disc prolapse, exerting a compressive action on the dural sac. Nonoperative, medical treatment was successful and a complete disappearance of symptoms was observed after 6 weeks, without recurrence during a 36-months follow-up. PMID- 7885968 TI - Cefepime. AB - Cefepime is a potent, broad-spectrum, fourth-generation cephalosporin with enhanced activity against most gram-positive aerobic bacterial pathogens and many gram-negative aerobic bacteria that are resistant to other cephalosporins. The drug's zwitterionic structure contributes to more rapid penetration of gram negative bacterial cell membranes, and its low affinity for most type I beta lactamases leads to significantly reduced enzymatic degradation compared with other cephalosporins. Cefepime has a good toxicity profile, with minor gastrointestinal and central nervous system symptoms being most prevalent. At dosages ranging from 1-2 g every 8-12 hours, it is an alternative option for infections of the lower respiratory tract, urinary tract, and skin and skin structures, as well as febrile episodes in neutropenic patients with cancer, and bacteremia or septicemia in critically ill patients. PMID- 7885969 TI - Evaluating postoperative nausea and vomiting. PMID- 7885971 TI - Defining and achieving optimum therapeutic goals in critically ill patients. AB - Patients who are critically ill with sepsis, shock, respiratory failure, trauma, or major surgical procedures may have reduced morbidity and mortality when hemodynamic and oxygen transport variables are augmented to values higher than those traditionally considered normal. Lactate production and suboptimum oxygen transport values are associated with anaerobic metabolism and insufficient tissue oxygenation. Since lactate can be a marker of inadequate tissue oxygenation, serial lactate measurements may be useful in individualizing therapy to reverse tissue hypoxia. Optimum hemodynamic and oxygen transport values are highly individual, and no accepted method has been established for guiding therapy. These values, together with plasma lactate concentrations, may assist in individualizing therapy in critically ill patients. No consensus can be reached at this time as to which specific therapeutic end points are optimal, how to achieve these end points, and which subset of patients will benefit from this therapy. PMID- 7885970 TI - Prolonged, but not diminished, zidovudine absorption induced by a high-fat breakfast. AB - STUDY OBJECTIVE: To determine the effect of a high-fat breakfast on single-dose, zidovudine (ZDV) pharmacokinetics. DESIGN: Open-label, randomized, crossover study. PATIENTS: Eighteen asymptomatic subjects (12 men, 6 women) infected with the human immunodeficiency virus (mean CD4 cell counts of 512 +/- 178/mm3). INTERVENTIONS: Subjects received single 100-mg oral doses of ZDV as follows: after an 8-hour fast (treatment A), with a high-fat breakfast (treatment B), and 3 hours after a high-fat breakfast (treatment C). MEASUREMENTS AND MAIN RESULTS: The high-fat breakfast significantly reduced the mean (coefficient of variation) maximum plasma concentration (Cmax) from 806 (55%) ng/ml with treatment A to 341 (47%) and 424 (42%) ng/ml with treatments B and C, respectively. The time to Cmax was significantly prolonged from 0.68 (30%) hours with treatment A to 1.7 (54%) and 1.3 (42%) hours with treatments B and C, respectively. Area under the plasma ZDV concentration-time curve (AUC) was not statistically different across the study treatments. Men had significantly lower (35%) renal clearances of both ZDV and its glucuronide metabolite than women. CONCLUSIONS: When ZDV was given either with or 3 hours after a high-fat breakfast, its absorption was prolonged and Cmax was reduced relative to fasting. However, systemic exposure, as indicated by AUC, was unchanged. PMID- 7885972 TI - Review of the symptomatic treatment of diabetic neuropathy. AB - References were selected from a MEDLINE search from 1966-1993 for literature evaluating the drug therapy of diabetic peripheral neuropathy (DPN). The search was limited to studies evaluating symptomatic treatment, and methods were developed to include only well-designed clinical trials. Many recommendations for the symptomatic treatment of DPN appear in the medical literature, but are frequently based on case reports, information extrapolated from other neuropathic pain syndrome models, or treatment protocols lacking scientific methods. These recommendations include antidepressants, sodium channel antagonists, topical capsaicin, and miscellaneous agents. Anti-depressants are considered to be the first choice in these patients. Factors to consider in establishing a regimen are interpretation of studies, adverse drug effects, drug-drug and drug-disease interactions, convenience of administration, and cost of therapy. Potentially effective alternatives were determined from the reviewed trials. PMID- 7885973 TI - Reversal of the electrocardiographic effects of cocaine by lidocaine. Part 1. Comparison with sodium bicarbonate and quinidine. AB - Based on modulated receptor concepts, an agent with fast on-off sodium channel binding properties (e.g., lidocaine) may reverse the effects of a drug with slow on-off kinetics (e.g., cocaine) through competition for a single receptor site on the sodium channel. We compared the effects of two drugs with different sodium channel-binding kinetics with those of sodium bicarbonate, a known antidote, on cocaine-induced slowing of ventricular conduction. Electrocardiographic (ECG) intervals were recorded before and after the addition of cocaine 30 microM in 26 isolated, Tyrode-perfused guinea pig hearts. The effects of the three potential antidotes were then analyzed: equimolar lidocaine (8 hearts), equimolar quinidine (6), and sodium bicarbonate (8). Cocaine significantly increased all ECG intervals. The addition of lidocaine to cocaine-containing perfusate decreased QRS duration from 42 +/- 3 to 29 +/- 3 msec (p < 0.01), a 60% reversal. Addition of sodium bicarbonate to increase the pH of the perfusate from 7.37 +/- 0.09 to 7.52 +/- 0.08 (p < 0.01) decreased the QRS duration from 38 +/- 4 to 30 +/- 6 msec (p < 0.01), a 47% reversal. Addition of quinidine 30 microM augmented the effects of cocaine: QRS increased from 40 +/- 6 msec to 54 +/- 9 msec (p < 0.01). Consistent with modulated receptor concepts, lidocaine reverses slowed ventricular conduction due to cocaine. The magnitude of this reversal is similar to that due to sodium bicarbonate. The potential of fast on-off agents to serve as antidotes for cocaine-induced arrhythmias requires further study. PMID- 7885974 TI - Reversal of the electrocardiographic effects of cocaine by lidocaine. Part 2. Concentration-effect relationships. AB - Ventricular arrhythmias due to cocaine may be related to its ability to slow ventricular conduction or prolong repolarization. We previously showed that lidocaine reversed QRS prolongation due to cocaine. The purposes of these experiments were to characterize cocaine's concentration-effect relationship on both ventricular conduction and repolarization, and to determine the effects of lidocaine on these relationships. The effects of lidocaine on cocaine-induced electrocardiographic changes were studied in 20 isolated, Tyrode-perfused guinea pig hearts. Variables at cocaine concentrations ranging from 3-195 microM were measured and repeated in the presence of a fixed concentration of lidocaine 30 microM. Using nonlinear regression analysis, the sigmoid Emax and simple Emax models were fit to cocaine concentration versus percentage change in QRS plots. Measures of best fit indicated that this relationship was best described by the sigmoid Emax model. Compared with cocaine alone, the curve for cocaine with lidocaine showed a greater EC50 (concentration at 50% of maximum effect) (59 vs 100 microM) but similar Emax (371 vs 367%), consistent with competition. Similar values were obtained from the linear transformation of the data. Cocaine concentration versus percentage change in the JTc interval showed a biphasic effect: concentrations below 65 microM prolonged JTc, but those above 65 microM had no effect or decreased JTc. In contrast to changes in QRS, addition of lidocaine increased the effects of cocaine on JTc: area under the concentration effect curve for cocaine alone was 720 versus 859 microM% for cocaine with lidocaine. Lidocaine reverses cocaine-induced slowed ventricular conduction through competition for binding, but it appeared to increase cocaine-induced prolongation of repolarization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7885975 TI - An assessment of recent pharmacy graduates' knowledge and competency, professional practice functions, and involvement in pharmacy teaching programs. AB - STUDY OBJECTIVES: To determine self-evaluated professional knowledge and competency, functions, demographic information, lifelong learning, degree and training status, practice sites, involvement in pharmacy teaching programs, and salary for recent pharmacy graduates. DESIGN: A survey of recent Bachelor of Science (B.S.) pharmacy graduates of the University of Wisconsin School of Pharmacy. MEASUREMENTS AND MAIN RESULTS: A total of 371 B.S. pharmacy graduates (55% response rate) provided information. Graduates who had an advanced degree or training (from many programs) after completing their B.S. pharmacy degree, and those who were teaching in pharmacy programs generally had higher self-rated levels of knowledge and competencies. Hospital pharmacists spent less of their work time in dispensing activities (33.82% +/- 30.39%) than community pharmacists (61.04% +/- 19.97%; t = 8.78, df = 288, p < 0.001); community pharmacists spent twice as much of their work time counseling and educating patients (16.65% +/- 10.47% vs 7.13% +/- 7.39%; t = 9.06, df = 288, p < 0.001). The amount of time pharmacists spent in dispensing functions had a negative association with knowledge and competencies in the sections on pharmacokinetic and disease process (r = -0.277, p < 0.01), patient communications (r = -0.272, p < 0.01), and administrative and economic aspects of practice (r = -0.210, p < 0.01) for all respondents. Pharmacists reported that they spent 13.78 +/- 14.06 hours per month outside work in professional lifelong learning. There was a negative association between the time pharmacists spent dispensing and the time they spent in professional lifelong learning (r = -0.239, p < 0.001), and a positive relationship between the time spent in such learning and the time providing information to prescribers and other health care professionals (r = 0.214, p < 0.001), monitoring patients (r = 0.216, p < 0.001), and performing primary care activities (r = 0.176, p < 0.001). Graduates reported a mean yearly salary of $46,879 +/- $8183. More hospital pharmacists were involved in teaching (48, 37%) than those practicing in a community setting (19, 12%). CONCLUSIONS: Practice site, advanced degree or training, lifelong learning, involvement in teaching programs, and time spent in various professional functions were associated with pharmacists' self-rated knowledge and competencies. PMID- 7885976 TI - Patients' perceptions of increased pharmacy contact. AB - This prospective, randomized study was conducted to determine if increased patient contact between pharmacists and patients would result in greater patient awareness and satisfaction with their hospital stay and particularly with pharmacists and pharmacy services. Eligible patients were randomized to receive either the usual pharmacy care with minimum contact with the pharmacist, or expanded services based on increased contact with the pharmacist. A questionnaire was used to determine patient awareness and satisfaction. Statistically significant differences were found between the groups on awareness and satisfaction with pharmacy services scales as well as total scores. Total patient scores were highly reliable, with an alpha coefficient of 0.87. In addition, comments by patients in the group with increased contact were overwhelmingly positive, in contrast to those receiving usual care. Patients desire and appreciate greater contact with pharmacists. PMID- 7885977 TI - Effect of nebulized albuterol on serum potassium and cardiac rhythm in patients with asthma or chronic obstructive pulmonary disease. AB - STUDY OBJECTIVE: To evaluate the metabolic and cardiopulmonary effects of nebulized albuterol in patients suffering moderate to severe exacerbations of asthma or chronic obstructive pulmonary disease. DESIGN: Open-label, prospective study. SETTING: The emergency department of a university medical center. PATIENTS: Ten patients with moderate to severe exacerbation of asthma. INTERVENTIONS: Each patient received nebulized albuterol 2.5 mg for approximately 10 minutes. MEASUREMENTS AND MAIN RESULTS: Serum potassium, heart rate and rhythm, blood pressure, and pulmonary function were measured before treatment and every 15 minutes for 2 hours after treatment. Serum potassium concentrations decreased significantly (p < 0.05) within 75 minutes after initiation of treatment, from a baseline value of 4.5 +/- 0.6 mEq/L (range 3.5-5.5 mEq/L) to 3.7 +/- 0.5 mEq/L (range 2.8-4.4 mEq/L) at the end of the collection period (120 minutes). Forced expiratory volume in 1 second significantly increased over time in patients with asthma (p < 0.05). No statistically significant changes in blood pressure, heart rate, or corrected QT intervals occurred. Pre-emergency department use of a beta 2-agonist by metered-dose inhaler was not associated with a decreased serum potassium on admission. CONCLUSIONS: Nebulized beta 2 agonists are generally efficacious and safe in patients with acute bronchospasms. However, close monitoring of serum electrolytes, heart rate, and rhythm in patients at risk (elderly, those with pre-existing cardiac disease) is advised before these individuals receive repeat doses by continuous aerosol administration. PMID- 7885979 TI - Research guidelines for the Pharm.D. practitioner. PMID- 7885978 TI - Ampicillin-sulbactam versus cefoxitin for prophylaxis in high-risk patients undergoing abdominal surgery. AB - This double-blind study compared ampicillin-sulbactam 3 g versus cefoxitin 2 g in 136 adult patients at risk for developing an infection after abdominal surgery. Separate randomization schedules were used for colorectal, upper gastrointestinal/biliary, and other abdominal procedures. Study antibiotics were administered within 30 minutes before incision and repeated 6 hours later. Patients having colorectal surgery received a third dose of antibiotic 6 hours after the second. Efficacy evaluations were made on 123 patients, 62 in the ampicillin-sulbactam group and 61 in the cefoxitin group. The overall postoperative infection rates were 12.9% for ampicillin-sulbactam and 9.8% for cefoxitin (p > 0.05); one wound infection occurred in each group. Adverse events were experienced by 13.2% of the ampicillin-sulbactam and 19.1% of the cefoxitin recipients (p > 0.05). Cost-minimization analysis revealed that ampicillin sulbactam was a cost-effective alternative to cefoxitin for the prevention of infection after abdominal surgery. PMID- 7885980 TI - Establishing and evaluating clinical pharmacy services in primary care. American College of Clinical Pharmacy. PMID- 7885981 TI - Proteinase inhibitors: the result of rational drug design. Introduction. PMID- 7885982 TI - Use of proteinase inhibitors in clinical practice. AB - Drugs that are currently available for the treatment of human immunodeficiency virus (HIV) infection, the nucleoside analogs, are limited in their usefulness both by the fact that they all act at the same site of virus replication and because of the development of drug resistance. One of the major areas of HIV research therefore has been the development of new drugs, with the proteinase inhibitors showing promise in clinical trials. Proteinase inhibitors act at a different stage in the virus life cycle and are relatively nontoxic. Saquinavir mesylate (Hoffmann-La Roche, Nutley, NJ) is the most extensively tested and appears to have activity, as assessed by immunologic and virologic methods in small trials and in one AIDS Clinical Trials Group study. Continuing research in phase 3 studies will help to clarify the most appropriate use for this drug. PMID- 7885983 TI - Rational drug design: the proteinase inhibitors. AB - Human immunodeficiency virus (HIV) proteinase is a promising target for the rational development of drugs against the acquired immunodeficiency syndrome (AIDS), since this enzyme is necessary for viral maturation, and its inhibition could lead to cessation of viral replication. Rational drug design combines chemical synthesis of compounds with structure determination methods, including protein crystallography. When the crystal structure of the HIV proteinase was determined, many research laboratories began designing drugs that would be effective inhibitors of the enzyme, and many such inhibitors were produced. Once that work was initiated, refined, and completed in the laboratory, other issues, such as specificity and bioavailability, became important. The clinical utility of such compounds is the final and most important consideration. Analysis of many agents for which structural formulas have been determined, and comparison of such formulas, provide valuable lessons for the continuing work on this enzyme and for future programs of rational drug design. PMID- 7885984 TI - [Perspectives on practical use of biotechnologic advances, molecular biology and cellular engineering in clinical hematology]. PMID- 7885985 TI - [Excretion of beta-2-microglobulin and Tamm-Horsfall protein in patients undergoing a conditioning regimen before bone marrow transplantation]. AB - This study aimed assess function of renal tubules in patients undergoing conditioning regimen before bone marrow transplantation. The examined group comprised 19 patients. 13 of them underwent autologuous bone marrow transplantation (ABMT), or autologuous peripheral blood stem cells transplantation (APBSCT). These patients were treated with Cyclophosphamide (Cy) (120 mg/kg), Etoposide (1.6-1.8 g/m2) and Carmustine (400-450 mg/m2). The remaining 6 patients underwent allogenic bone marrow transplantation (BMT). They were treated with Cy 200 mg/kg or with Cy 120 mg/kg and Busulfan 16 mg/kg (doses given are the total amount or respective drugs were administered during the whole conditioning regimen). Urinary excretion of beta-2MB and THP was assessed a) before the conditioning regimen was started, b) one day before completion of it, and c) one day before bone marrow transplantation. In ABMT/APBSCT patients urinary excretion of beta-2-MG was significantly higher before and during conditioning regimen as compared with baseline value (3309 +/- 1123.7 vs 3919 +/- 1417.8 vs 246.7 +/- 50.3 mg/24h, respectively, p < 0.05). Urinary excretion of THP in these patients was significantly higher only during the conditioning regimen (90.6 +/- 14.3 vs. 30.4 +/- 6.24 mg/24h, p < 0.0002). In BMT patients conditioning regimen was followed by similar but less marked changes of urinary excretion of beta-2-MG and THP as compared with ABMT/APBSCT patients. CONCLUSIONS: 1. Conditioning regimen do influence significantly function of proximal and distal renal tubules. 2. The extent of disturbed function of renal tubules seems to depend on kind of medication that is given during the conditioning regimen. PMID- 7885986 TI - [Seeking a correlation between functional and imaging findings in patients after acute alcoholic pancreatitis]. AB - The aim of the present study was to correlate the imaging and functional findings in patients who recovered from acute alcoholic pancreatitis (a.a.p.). 35 patients, 4-7 years following acute alcoholic pancreatitis underwent: secretin cerulein test (SCT), ultrasound (US) and computed tomography (CT) of pancreas. Control group comprised 15 patients in which endoscopic, imaging and functional findings excluded organic G.I. disease. Exocrine function impairment was stated in 65.7%. US revealed pancreatic changes in 37.1% patients and CT--in 45.7%. Significant correlation between the degree of structure abnormalities in imaging techniques nad the severity of exocrine pancreatic function impairment was found (p < or = 0.05). However, in about one third of the patients studied, changes revealed in imaging techniques were not accompanied by function impairment and vice versa. Patients after acute alcoholic pancreatitis should be followed-up to early recognize and treat the revealed changes. Imaging and functional methods should be considered as strictly complementary. PMID- 7885987 TI - [Fibrinolytic and lipid disturbances in patients with nephrotic syndrome]. AB - Some fibrinolytic parameters (euglobulin clot lysis time, activities and antigens of tissue plasminogen activator and inhibitor), serum lipids and their mutual relations were studied in 31 patients with nephrotic syndrome. Euglobulin clot lysis time was found to be significantly prolonged in patients with nephrotic syndrome when compared to control group. Activity and antigen of tissue plasminogen activator were significantly higher in healthy volunteers, whereas nephrotic patients activity of tissue plasminogen activator inhibitor was significantly higher than in controls. Cholesterol, LDL and VLDL were elevated in patients with nephrotic syndrome when compared to controls. LDL was found to be positively related to both tissue plasminogen activity and antigen in nephrotic patients. Serum cholesterol correlated positively with albuminemia in these patients. PMID- 7885988 TI - [Effect of hemodialysis with cuprophane and polysulfone membranes on counts of leukocytes, granulocytes, monocytes, lymphocytes and lymphocyte subsets]. AB - In patients with chronic renal failure treated with haemodialysis many disorders of specific and unspecific immunity were observed. Several different parameters such as direct interaction with dialyzer membrane, hypersensitivity to components within the membrane, complement activation, or presence of endotoxins in the dialysis fluid or water supply can activate the immune system during haemodialysis and cause immunity disorders. This study aimed to compare the biocompatibility of two different dialysis membranes on the ground of the influence on the counts of immunity cells in the first hour of haemodialysis when the interaction between blood and membrane were the greatest. In 18 patients with CRF granulocytes, monocytes, lymphocytes B and T, T4 and T8 cells were counted just before haemodialysis, 15 minutes and 60 minutes after the start of haemodialysis. In all patients the investigation was done first using the cuprophane dialysis membrane and then using polysulfone dialysis membrane. The cell populations were differentiated by flow cytometry on Fascan using the conjugated monoclonal antibodies. During the first 15 minutes of haemodialysis with cuprophane membrane the amount of all investigated cells populations decreased significantly. With polysulfone membrane only monocytes decreased significantly in the first 15 minutes of haemodialysis. These results indicate that the polysulfone membrane is more biocompatible than the cuprophane one and suggest that using the biocompatible membranes some disorders of immunity system in this patients can be prevented. PMID- 7885989 TI - [Anemia and erythropoietin level in some hematology malignancies]. AB - Pathogenesis of anemia in patients with myeloma, low grade lymphoma and acute leukaemia was the aim of the study. Erythropoietin (Epo) serum level was detected according to ELISA test. Significant increase of Epo serum level in 13 myeloma and 30 low grade lymphoma patients was found. In 21 acute leukemia cases the Epo serum level was significantly increased (disproportional to Hb concentration). CONCLUSION: in the studied myeloma and low grade lymphoma patients anemia did not depend on defective Epo secretion. Significant increase of Epo serum level in acute leukaemia, strongly suggested additional stimulation mechanism for hormone synthesis. Further studies of this mechanism are needed. PMID- 7885990 TI - [Portal vein thrombosis. Etiology, diagnosis and treatment]. AB - The authors present 225 patients with various forms of portal system venous thrombosis (PSVT), of various origin and etiology. The largest group (120 patients) were the young people suffering from portal hypertension due to pre hepatic venous obstruction of uncertain etiology, lasting since childhood. The next group consisted of 75 patients with liver cirrhosis coexisting with PSVT. In other cases PSVT was diagnosed as coincident with: Budd-Chiari Syndrome (8 cases), liver tumors (9 cases), chronic pancreatitis (3 cases) and polycythaemia (2 cases). In 3 cases PSCT developed postoperatively and in 5 cases after oral contraceptives. Diagnosis of coexisting PSVT deteriorates the prognosis in liver cirrhosis. The overall mortality was 16%. The course of the disease depends on extensiveness and dynamism of thrombosis, but consequently leads to the development of portal hypertension. The most effective diagnostic procedures are: CT and USG with Doppler flowmetry. Bleeding esophageal varices require either sclerotherapy or surgical treatment--decompressive shunts or "non-shunt" procedures. In the cases of recent thrombosis, without bleeding varices, thrombolytic therapy appears to be effective. PMID- 7885991 TI - [Endothelin in ischemic heart disease]. PMID- 7885993 TI - [A rare case of renal osteodystrophy as a consequence of end stage renal failure and secondary hyperparathyroidism]. AB - A case of rare facial dysplasia due to renal osteodystrophy of end stage renal failure is described in a 19-year old boy treated with chronic haemodialyses. The favourable effects of surgical correction are shown. PMID- 7885992 TI - [A case of spontaneous non-traumatic rupture of the kidney during renal vessel thrombosis]. AB - We present a case of spontaneous non-traumatic rupture of kidney in a 78-year old patient, probably caused by renal vessel thrombosis. In spite of the relatively good prognosis in early diagnosis, the outcome of presented case was fatal because of late surgical complications. PMID- 7885994 TI - [Current view on the pathogenesis of thromboangiitis obliterans (Buerger's disease)]. PMID- 7885995 TI - [Dr. Edmund Faustyn Biernacki and his discovery (on the centennial discovery of the erythrocyte sedimentation rate)]. PMID- 7885996 TI - [Report from the symposium "Portal Hypertension" in Freiburg--Falk Symposium nr. 79, 17-19.06.94]. PMID- 7885997 TI - [Diagnostic criteria of analgesic nephropathy in hemodialyzed patients with chronic renal failure]. PMID- 7885998 TI - Analysis of the mouse tyrosinase promoter in vitro and in vivo. AB - The restricted expression of the tyrosinase gene in cells producing pigment suggests the presence of cis-regulatory elements and trans-acting tissue-specific factors. Since 270 bp upstream of the transcriptional start site contain sufficient information for tissue-specific and developmentally regulated expression, we confined our analyses to this region. In this article, we discuss the recent results we have obtained on the regulation of the mouse tyrosinase gene expression demonstrating the existence of one negative and two positive acting elements in vitro. We have evidence that the positive elements do not determine pigment production in vivo but rather modulate transcription of the mouse tyrosinase gene. PMID- 7885999 TI - Identification of nuclear factors that bind to the mouse tyrosinase gene regulatory region. AB - Several nuclear factors that interact with sequences in the 5' flanking region of the mouse tyrosinase gene were identified using band shift and methylation interference assays. One of these factors bind to an AT-rich sequence, TATCAATTAG, located at -183 base pairs upstream of the transcription start site. To isolate cDNA clone encoding this DNA binding protein, we have screened a lambda gt11 cDNA expression library prepared from mouse melanocyte cell line with a labeled oligonucleotide probe containing its binding site. Complementary DNA clones encoding mouse high mobility group protein HMG-I and its isoform HMG-Y were obtained. HMG-I(Y) is a low molecular size, basic nuclear protein that binds specifically to AT-rich region of double-stranded DNA in vitro. In Northern blot analysis the level of HMG-I(Y) mRNA expression did not correlate with that of tyrosinase or TRP-1. Although the amount of HMG-I(Y) transcripts has no apparent influence on the mouse tyrosinase gene expression, it is possible that HMG-I(Y) binds to the 5' flanking sequence of the tyrosinase gene as an auxiliary factor, and facilitates the binding and activity of other transcription factors. PMID- 7886000 TI - Analysis of tyrosinase mutations associated with tyrosinase-related oculocutaneous albinism (OCA1). AB - Mutations of the tyrosinase gene associated with a partial or complete loss of enzymatic activity are responsible for tyrosinase related oculocutaneous albinism (OCA1). A large number of mutations have been identified and their analysis has provided insight into the biology of tyrosinase and the pathogenesis of these different mutations. Missense mutations produce their effect on the activity of an enzyme by altering an amino acid at a specific site. The location of these mutations in the peptide can be used to indicate potential domains important for enzymatic activity. Missense mutations of the tyrosinase polypeptide cluster in four regions, suggesting that these are important functional domains. Two of the potential domains involve the copper binding sites while the others are likely involved in substrate binding. More critical analysis of the copper binding domain of tyrosinase can be gained by analyzing the structure of hemocyanin, a copper-binding protein with a high degree of homology to tyrosinase in the copper binding region. This analysis indicates a single catalytic site in tyrosinase for all enzymatic activities. PMID- 7886001 TI - Tyrosinase isoenzymes: two melanosomal tyrosinases with different kinetic properties and susceptibility to inhibition by calcium. AB - Two forms of tyrosinase from B16 mouse melanoma were identified by nonreducing SDS-PAGE after solubilization of crude melanosomal preparations with the nonionic detergent Brij 35. These forms, named LEMT and HEMT (low and high electrophoretic mobility tyrosinase, respectively), were purified by a combination of differential detergent extraction and chromatographic techniques. They displayed tyrosine hydroxylase and dopa oxidase activity and were stereospecific and sensitive to phenylthiourea, providing that they are true tyrosinases. However, based on its kinetic parameters, HEMT is a much more efficient enzyme. Immunoprecipitation and Western blots performed with the specific antibody alpha PEP1, directed against the b protein carboxyl terminus, suggested that LEMT is identical to the b protein. Both forms of tyrosinase were noncompetitively inhibited by Ca2+ at physiologically relevant concentrations. However, the b protein was apparently more susceptible, since maximal inhibition was reached at lower Ca2+ concentrations for LEMT. Moreover, binding of Ca2+ to the tyrosinases resulted in a noticeable thermal destabilization of the enzymes, which was also more pronounced for LEMT. PMID- 7886002 TI - The DHICA oxidase activity of the melanosomal tyrosinases LEMT and HEMT. AB - Although melanins can be formed in vitro by the unique action of tyrosinase on L tyrosine, it is now well accepted that other enzymes termed tyrosinase-related proteins are involved in mammalian melanogenesis. However, some aspects of their roles in the regulation of the pathway are still unknown. The action of dopachrome tautomerase on L-dopachrome yields DHICA, a stable dihydroxyindole with a low rate of spontaneous oxidation. However, DHICA is efficiently incorporated to the pigment, as judged by the high content of carboxylated indole units in natural melanins. Therefore, the fate of this melanogenic intermediate and the mechanisms of its incorporation to the melanin polymer are major issues in the study of melanogenesis. We have recently shown that mouse melanosomes contain two electrophoretically distinguishable tyrosinase isoenzymes, LEMT and HEMT, that can be purified and completely resolved (Jimenez-Cervantes et al., 1993a). Herein, we have compared the ability of these tyrosinases to catalyze DHICA oxidation. Although highly purified LEMT shows a very low specific activity for dopa oxidation in comparison to HEMT, it is able to catalyze DHICA oxidation. However, the DHICA oxidase activity of HEMT was very low, if significant. The ability of purified LEMT to catalyze DHICA oxidation was abolished by heat, trypsin, or phenylthiourea treatments. LEMT acting on DHICA caused the formation of a brownish soluble color similar to DHICA-melanin. Immunoprecipitation of the DHICA oxidase activity of LEMT by specific antibodies suggests that this activity corresponds to TRP1. These results indicate that LEMT, most probably identical to the product of the b locus, is a tyrosinase having a specific DHICA oxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886003 TI - The mouse brown (b) locus protein functions as a dopachrome tautomerase. AB - The mouse b locus controls black/brown coat coloration. Its product, the b protein or TRP-1, has significant homology to tyrosinase, and this has led to suggestions that the b-protein is itself a melanogenic enzyme. In order to investigate its function, we have used lines of mouse fibroblasts stably expressing the b-protein. We were unable to confirm previous reports that the b protein has tyrosinase or catalase activity, but detected stereospecific dopachrome tautomerase activity in b-protein-expressing fibroblasts. This dopachrome tautomerase binds to Concanavalin A-Sepharose, and the major product of its action on L-dopachrome is 5,6-dihydroxyindole-2-carboxylic acid, as expected for the mammalian enzyme. Since this activity is not present in untransfected fibroblasts we conclude that the b-protein has dopachrome tautomerase activity. Further supporting evidence comes from the analysis of melanin metabolites produced by fibroblasts expressing tyrosinase alone, or in combination with the b-protein. Culture medium from the line expressing both proteins contains significant amounts of methylated carboxylated indoles, such as 6-hydroxy-5-methoxyindole-2-carboxylic acid, which would be expected in cells with an active dopachrome tautomerase. The levels of these compounds in medium from cells expressing tyrosinase alone are approximately 20-fold lower, and not significantly above background. Hence, it appears that the b-protein acts as a dopachrome tautomerase in vivo as well as in vitro. PMID- 7886004 TI - Coordinated mRNA and protein expression of human LAMP-1 in induction of melanogenesis after UV-B exposure and co-transfection of human tyrosinase and TRP 1 cDNAs. AB - In order to better understand the cascade of melanogenic events in melanocytes, this report has introduced our two recent approaches for the expression of melanogenesis/or melanosome-associated genes and encoded proteins in melanocytes (melanoma cells) after repeated exposure to UV-B and after cotransfection of two human genes, i.e., tyrosinase and tyrosinase-related protein-1 (TRP-1). Repeated exposure of UV-B (2.5-5.0 mJ/cm2) caused not only upregulation of tyrosinase and TRP-1 genes but also coordinated increase in the gene and protein synthesis expression of Lamp-1 (lysosome-associated membrane protein-1). When COS-7 kidney cells and amelanotic melanoma (C32 and SK-MEL-24) and melanotic melanoma (G361 and SK-MEL-23) cells were exposed to cotransfection of human tyrosinase and TRP-1 cDNAs, there was also an increased expression of Lamp-1 mRNA and protein along with tyrosinase activation and new melanin synthesis. Importantly, single transfectants of human tyrosinase cDNA revealed marked cellular degeneration, whereas this degeneration was not seen in single transfectants of TRP-1 cDNA or cotransfectants of human tyrosinase and TRP-1 cDNAs, indicating that TRP-1 prevented, along with Lamp-1, programmed death of melanocytes after transfection of tyrosinase gene. The coordinated expression of TRP-1 and Lamp-1 was further confirmed by antisense oligodeoxynucleotide hybridization experiment against Lamp 1 gene, showing the decreased expression of TRP-1 as identified by three different types of anti-TRP-1 monoclonal antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886005 TI - Effects of ultraviolet irradiation on the cell cycle. AB - Cultured mouse Cloudman melanoma cells, EMT6 breast carcinoma cells, and 3T3 fibroblasts all accumulated in the G2/M phase of the cell cycle when exposed to UVB radiation. The effects of UVB were maximal at 20-30 mJ/cm2 for all three cell lines, and could be observed by flow cytometry as early as 12 hr post irradiation. It has been known since the mid-1970s that MSH receptor binding activity is highest on Cloudman melanoma cells when they are in the G2/M phase of their cycle. Here we show that either UVB irradiation or synchronization of Cloudman cells with colchicine results in a stimulation of MSH binding within 24 hr following treatment, a time when both treatments have resulted in accumulation of cells in the G2/M phase of the cycle. Furthermore, the two treatments performed together on the melanoma cells stimulated MSH receptor activity to the same extent as either treatment performed separately, suggesting that each may be influencing MSH receptor activity solely through a G2/M accumulation of cells. Together, these results raise the possibility that an increase in the number of cells in the G2 phase of the cell cycle is a generalized cellular response to injury, such as UV irradiation. However, in the case of pigment cells this response includes a mechanism for increasing melanin formation, i.e., increased MSH receptor activity. Should this be the case, similar G2/M "injury responses" of other cell types might be expected, consistent with their differentiated phenotypes. PMID- 7886006 TI - Demonstration of voltage-dependent and TTX-sensitive Na(+)-channels in human melanocytes. AB - The electrophysiological properties of cultured human melanocytes were investigated using the whole-cell configuration of the patch-clamp technique. Depolarizations to membrane potentials more positive than -30 mV resulted in the rapid development ( < 1 ms to peak) of an inward current. The maximum peak current was observed at +10 mV and reached an average amplitude of about 270 pA. During the depolarizations, the current inactivated with a time constant of about 2 ms. The current was abolished by the addition of 0.3 microM tetrodotoxin, a blocker of voltage-gated Na(+)-channels, and disappeared when Na+ was omitted from the extracellular medium. In addition, the melanocytes contain at least two types of outward K(+)-current. The first type, observed in every cell, was highly sensitive (Ki 1 mM) to the K(+)-channel blocker TEA, required depolarizations beyond zero to be activated and did not inactivate. The second type was less regularly observed (10% of the cells). This current activated at more negative voltages (-20 mV), was resistant to TEA (20 mM) but was blocked by 2 mM 4 aminopyridine and inactivated rapidly during depolarizations. We conclude that human melanocytes are equipped with voltage-dependent Na(+)-channels, a delayed rectifying K(+)-current and a K(+)-current similar to the A-current in neurones. PMID- 7886007 TI - P53 mutation and c-fos overexpression are associated with detection of the antigen VLA-2 in human melanoma cell lines. AB - In this study, we examined the expression of c-fos, c-myc, mutant c-Ha-ras and mutant p53 proteins in three normal human melanocyte cell lines and the following 12 melanoma cell lines: M5, Mewo, A375, Bro, Mel 2a, O-Mel II, IgR 39, SkMel-13, 19, -28 Mel-57 and NKI-4, using an immunohistochemical assay (APAAP). An effort was made to correlate oncogene expression with growth parameters, differentiation antigens (HMB-45, vla-2, k.1.2.58, HLA-DR, HLA-I), and pigmentation. All melanocyte cell lines were negative for the oncogenes examined, whereas six of the melanoma cell lines were found also positive (three for c-fos, two for c-myc, one for c-Ha-ras, and four for p53). Three melanoma cell lines expressed one oncogene and three the combination c-fos/p53. These three melanoma cell lines were positive for the "late" tumor progression marker A. 1.43 (vla-2 adhesion molecule) and negative for the differentiation marker k. 1. 2. 58. Positivity for A. 1. 43 combined with negative staining for k. 1. 2. 58 was found in six out of the 12 cell lines. The observed oncogene expression correlated neither with growth parameters nor melanin content. The present findings revealed a coexpression of mutant p53 and c-fos proteins being associated with a highly malignant phenotype in melanoma cell lines. Further studies are necessary to clarify the significance of the above findings. PMID- 7886008 TI - p53 and PCNA expression in malignant melanomas of the head and neck. AB - Mutation in the p53 tumor suppressor gene is the most common genetic alteration in human cancer. As in mutant p53 the protein is stabilised and the half-life is extended, it becomes detectable by immunohistological staining. p53 immunoreactivity thus seems to be a potential biomarker for the assessment of the oncogenic potential of malignant melanomas. In 103 tissue sections of primary and metastatic malignant melanomas of the head and neck detectable levels of p53 were only found in 3 of the primary tumors and in none of the metastases. At the same time the proliferation status of the malignant melanoma lesions was determined using the cell cycle specific antibody PCNA. 55 primary and metastatic tumors were stained with a PCNA-MAb to determine the proliferation activity of the tumors. The results of our immunohistochemical investigation suggest that immunoreactivity of p53 cannot be used to determine the malignant potential of melanomas in the head and neck. PCNA staining showed that the majority of the tumors and metastases were proliferating rapidly. PMID- 7886009 TI - 211At-methylene blue in targeted radiotherapy of disseminated melanoma. AB - Targeted radiotherapy with 211At-methylene blue (211At-MTB) is a systemic treatment selectively directed at melanoma due to a high affinity of MTB to melanin synthesized in the tumor cells. Since MTB forms a strong complex with melanin, it is an effective carrier for a number of radioisotopes to be addressed to the tumor deposits of any size including individually dispersed melanoma cells. Thus, appropriately radiolabeled MTB can be used for either diagnosis or therapy of the neoplasm. As predicted and found in animal experiments, 211At-MTB is most effective therapeutically. Histopathological investigations showed that the highly pigmented 211At-MTB-treated tumors were characterized initially by perivascular oedema and hydropic degeneration of tumor cells followed by gradual development of extensive areas of coagulative necrosis. The necrotic tumor areas contained microvessels occluded by thrombi and tended to undergo microfocal calcification. Although melanoma-bearing animals successfully treated with 211At MTB did not reveal any adverse effects of the therapy, detailed toxicological studies were undertaken. No serious macro- or microscopic lesions were observed in normal organs of 211At-MTB treated mice. Only the relative number of small lymphocytes in the groin lymph nodes in a minority of animals was variably reduced, most often in conjunction with the treatment of highly, but not poorly, pigmented tumors. PMID- 7886010 TI - [Histological processing of iliac crest biopsies based on decalcification and paraffin embedding with reference to osteolytic and hematologic diagnosis]. AB - A survey is given of methods involving decalcification and paraffin embedding of iliac crest biopsy for osteological and haematological diagnostic procedures. In order to avoid shrinkage, loss of antigens, and fading of ferritin iron and enzymes, a fixative has been designed that is composed of an aqueous solution of calcium acetate (10(-1) M), glutaraldehyde (0.5%), and formaldehyde (1%; CGF). CGF-fixated specimens are decalcified in an aqueous solution of 10% di-sodium ethylene-diaminotetraacetate (EDTA) neutralized by tris[hydroxy]methylaminomethane and embedded in paraffin. Tissue prepared in this manner allows histochemical detection of naphthol AS-D chloroacetate esterase in the neutrophilic cell line and in tissue mast cells, tartrate-resistant acid phosphatase in hairy cells and certain other low malignant B-cell lymphomas, in Gaucher cells, and in osteoclasts, and a specific platelet esterase in megakaryocytes and leukaemic megakaryoblasts. A broad panel of antigens is well preserved. Beside haemosiderin, cytosolic ferritin can be detected by Perls' reaction in acute phase-stimulated macrophages. Emphasis is placed on the diagnostic impact of plasma cell siderosis and lysosomal sideroblastocytosis in haemochromatosis and in alcoholism respectively. A technique is presented to discriminate mineralized and non-mineralized bone even after decalcification. PMID- 7886011 TI - [The new Hannover method of synthetic embedding of bone marrow. Cold polymerization of methylmethacrylate]. AB - A patented low-temperature polymerization method for methylmethacrylate (MMA) infiltrated bone marrow biopsies is described: it has been developed from our previous MMA technique and is a patented procedure. Differences from the previous method are (1) removal of stabilizer from the MMA monomer before its application, (2) the use of a different starter, (3) avoidance of O2 influence during polymerization by means of vacuum exchange with N2, and (4) polymerisation in a water bath to draw off residual heat. After this procedure, all immunohistochemical reactions are possible provided that the previous fixation is adequate. The effects of different fixatives are reviewed briefly without detailed analysis. Technically, this plastic embedding can be performed at least as rapidly as the classic paraffin embedding after decalcification. The advantages over the latter method are: (1) the cells can be better differentiated because semi-thin sections can be made; (2) the immunoreactions can also be performed on the basis of semithin sections, which means they can be interpreted more easily; (3) morphometric analyses yield more reliable results because of the constant thickness of sections; (4) osteological examination of bone trabeculae, especially the search for mineralisation deficiencies, is possible; (5) the plastic embedding procedure is less dependent on individual instabilities in the quality of performance of the staff members involved. Furthermore, it is worth mentioning that the costs for additional equipment necessary remain below DM 100,000 including an excellent microtome. PMID- 7886012 TI - [Morphometry of megakaryocytes for supporting the histologic diagnosis of chronic myeloproliferative diseases]. AB - Morphometric analysis of sections of biopsy specimens from patients with chronic myeloproliferative disorders (CMPD) can complement the individual histological diagnosis and help to distinguish the four groups of CMPD. A total of 130 diagnostic biopsies from 29 cases of chronic myelocytic leukemia (CML.CT), 26 cases of (CML.MI), 28 of essential thrombocythemia (PTH), 26 cases of chronic megakaryocytic granulocytic myelosis (CMGM), and 21 of polycythemia vera (P. vera), and 30 from healthy control persons were evaluated morphometrically in sections of undecalcified plastic-embedded core biopsies. Clear distinctions were revealed in size of megakaryocytes, nuclear lobulation, clustering, and the nuclear size and shape of megakaryocytes. Nuclear size and cellular size were significantly less in CML (range of means of cellular size: 220-360 microns2) than in the other three Ph1-negative groups (range of means: 480-750 microns2). Nuclear lobulation was more distinct in PTH than in P. vera, and especially in CMGM. Clustering of megakaryocytes was more than twice as frequent in CMGM (8.0 10.5%) as in any of the other three groups (0.1-7.0%). Naked nuclei were more numerous in all groups of CMPD. The main topic of the study is the different size of megakaryocytes in the four main groups of CMPE, allowing a distinction between small-megakaryocytic Ph1-positive CML and large-megakaryocytic Ph1-negative forms of CMPD. PMID- 7886013 TI - [Cytogenetics and molecular studies confirm the histopathologic diagnosis of chronic myeloproliferative diseases]. AB - The histopathological classification of chronic myeloproliferative disorders can be supported by applying cytogenetics and molecular genetics to the analysis of bone marrow or blood cells, as demonstrated in 253 cases evaluated. The Philadelphia translocation (9;22) is the most important genetic parameter, being specific for chronic myeloid leukemia. Conventional methods for the detection of the t(9;22) are karyotyping and Southern blot analysis of the bcr gene. The newly established technique of fluorescence in situ hybridization (FISH) allows visualization of bcr-abl fusion even in non dividing cells. Molecular cytogenetics for t(9;22) yield results that are rapid and reliable as well as easily quantifiable. PMID- 7886014 TI - [The histological picture of anemia in bone marrow biopsies]. AB - A total of 41,553 bone marrow biopsies were collected for the Bone Marrow Registry from January 1989 to June 1994 included 6,366 taken from 5,011 patients referred because of unexplained anemia. An increasing percentage of biopsies submitted for examination are designated anemic: this rose from 7.2% in 1989 to 18.9% within the first 6 months of 1994, reflecting an increased need to find the reasons for anemic conditions. Histologically, seven main groups have been found: (1) myelodysplastic syndrome (MDS) accounting for 32% of all anemia patients seen, (2) infectious anemia (23.5%), (3) iron deficiency anemia ((22.7%), (4) hemolytic anemias (7.2%), (5) aplastic anemia (6.8%), (6) megaloblastic/pernicious anemia (5.0%), and (7) anemia due to bleeding (3.0%). These seven groups of anemia can be diagnosed in core biopsies on the basis of their particular histopathology, so that films of bone marrow smears are not always needed. PMID- 7886015 TI - [Histopathology and clinical aspects of primary myelodysplastic syndrome]. AB - The histopathology of bone marrow in primary myelodysplastic syndromes (MDS) is described, with reference to the FAB classification. Variants such as hypoplastic, thrombocythemic and fibrotic MDS are recognized from their histopathology and must be incorporated in the FAB classification. The clinical significance of hypoplastic, thrombocythemic and fibrotic variants is illustrated by the survival rates and leukemic transformation in these patients. Histopathological classification according to the FAB system corresponds with cytological classification, as proven by the distribution of the subtypes, blood values, leukemic transformation rates and survival times. Finally it is even possible to elaborate a prognostic score for survival based on histological features of diagnostic biopsies, which emphasizes the importance of histopathological examination of bone marrow in MDS patients. PMID- 7886016 TI - [Histopathology of Ph1-negative chronic myeloproliferative diseases]. AB - The Ph1-negative groups of chronic myeloproliferative diseases (CMPD) are described, and histopathological criteria that distinguish them from each other are given. These are based upon observations in primary biopsies from 2,331 patients with CMPDs among a total of 34,160 patients referred between 1 January 1989 and 30 June 1994 to the Bone Marrow Registry. These cases of CMPD break down into the main groups as follows: CML 23.2%, megakaryocytic myelosis consistent with agnogenic myeloid metaplasia 22.3%, essential thrombocythemia 22.1%, and polycythemia vera 20.4%; 12.0% of cases were unclassifiable. Histological progress in each group is characterized by (1) increasing number and pleomorphy of megakaryocytes, (2) increasing fibrosis, and (3) excess of blasts. These three features can be observed in diagnostic biopsies before any therapy. Therefore, it is recommended that such alterations be reported semiquantitatively. A staging system with four stages from 0 to 3 for each of the three features is introduced. Its application allows staging for the individual patient on the basis of diagnostic biopsies. PMID- 7886017 TI - [Histopathology of chronic myeloid leukemia in diagnostic biopsies of bone marrow]. AB - Histopathology of the bone marrow of diagnostic biopsies prior to any therapy is described in a total of 412 Ph1-positive patients. Special attention is paid to the distribution of megakaryocytes, increase of fibres and blasts, and occurrence of storing histiocytes of pseudo-Gaucher type. Megakaryocytes were significantly increased in 31.6% of diagnostic biopsies, myelofibrosis was found in 15.8%, significant increase of blasts in 2.4%. Pseudo-Gaucher cells were detected in 57.8% of a total of 412 biopsies. These histiological features are considered as an indication of the progress of the disease. A semiquantitative specification of CML by this criteria is described which can be performed rather reliably and defines the stage of CML at diagnosis prior to substantial treatment. PMID- 7886018 TI - [Primary brain lymphoma in acquired immunodeficiency syndrome. Immunophenotype and molecular pathologic characterization in stereotactic biopsy, autopsy and cerebrospinal fluid cytology]. AB - In this study we present morphological, cytological, immunophenotypical, and molecular genetic features of ten cases of AIDS-related primary brain lymphomas obtained as sterotactic biopsies, autopsy specimens, or cerebrospinal fluid samples. Histologically, a very characteristic perivascular and diffuse lymphomatous spread in the brain parenchyma was observed. By applying a highly sensitive in situ hybridization technique (ISH) using digoxigenin-labeled antisense riboprobes, abundant Epstein-Barr virus (EBV)-encoded small nuclear RNAs (EBER) transcripts could be demonstrated in each case studied. A combination of ISH with immunohistochemical staining for latent membrane protein (LMP-1) and EBV nuclear antigen-2 (EBNA-2) showed different patterns of EBV latency with a predominance of the broad spectrum (EBER+/EBNA-2+/LMP-1+). Clonal rearrangements of immunoglobulin heavy chain (IgH) genes were demonstrated in four cases using a sensitive polymerase chain reaction. In one patient the rearrangement pattern suggested biclonal lymphoproliferation. Our observations confirm the implication of the EBV in the etiology of AIDS-related primary malignant lymphomas of the brain. The demonstration of EBV gene products and clonal IgH rearrangements even in small biopsy samples is a useful tool for distinguishing between reactive and neoplastic lymphocytic infiltrates, which are frequently observed in brain and cerebrospinal fluid specimens obtained from AIDS patients. PMID- 7886019 TI - [Fatal vacuolar cardiomyopathy in chronic chloroquine drug treatment]. AB - Clinical and morphological findings recorded in an 81-year-old woman patient with a 45-year history of rheumatoid arthritis treated with long-term chloroquine therapy are reported. The cause of death was low cardiac output syndrome, which upon autopsy and postmortem toxicological analyses was classified as vacuolar chloroquine-induced cardiomyopathy. The pathogenesis and the morphological and clinical characteristics of cardiotoxic effects of chloroquine are reviewed. PMID- 7886020 TI - Human placenta: a direct target for cocaine action. AB - Use of cocaine during pregnancy is known to have harmful effects on the mother and her fetus. Currently available models describing the pathogenesis of these effects focus on the involvement of cocaine target systems, primarily the noradrenaline transporter, in the mother and the fetus. The placenta which lies between the mother and the fetus is considered only as a 'silent observer' in the whole process of cocaine-induced complications during pregnancy. Recent studies have, however, shown that the placenta expresses several cocaine target proteins such as the noradrenaline transporter, the serotonin transporter, and the sigma receptor. The functions of these proteins are significantly impaired in the presence of cocaine at concentrations known to exist in the plasma of cocaine users. These studies clearly show that the placenta itself is a direct target for cocaine action and that interaction of cocaine with its target proteins in the placenta plays an important role in the pathogenesis of cocaine-induced complications in the mother and her developing fetus. PMID- 7886021 TI - Functional characterization of L-alanine transport in a placental choriocarcinoma cell line (BeWo). AB - The substrate selectivity of the neutral amino acid transport systems of the b30 clone of the choriocarcinoma cell line (BeWo) were characterized. Three transport systems were identified in undifferentiated (without forskolin) and two transport systems in differentiated syncytial cells (with forskolin). In the undifferentiated b30 cells were two sodium-dependent systems with one having substrate selectivity patterns resembling system A (e.g. sensitive to MeAIB and a broad range of neutral amino acids) and the other resembling system ASC (e.g. MeAIB insensitive and inhibited by alanine, serine and cysteine). In addition a sodium-independent system was identified with characteristics resembling system l. The differentiated syncytial cells possessed the system A and system l-like activities but not the system ASC-like activity of the system A-like or system l like activities. The b30 clone is apparently an appropriate model for placental neutral amino acid transport systems. PMID- 7886022 TI - Comparative regulation of inhibin, activin and human chorionic gonadotropin production by placental trophoblast cells in culture. AB - In the present study, we investigated the roles of cyclic adenosine monophosphate (cAMP), intracellular calcium, glucocorticoids, protein kinase-C and gonadotrophin-releasing hormone (GnRH) in regulating human chorionic gonadotrophin (hCG), inhibin and activin production in cultured human term placental trophoblast cells. Inhibin and hCG were measured in conditioned media by radioimmunoassay, while putative forms of inhibin and activin were characterized by western blotting using affinity-purified antisera directed against the inhibin alpha- and beta A-subunits. Inhibin and hCG secretion were stimulated by dexamethasone (0.2 microM), GnRH (5-25 microM), calcium ionophore A23187 (0.2-1 microM), phorbol-12-myristate-13-acetate (22 nM) and epinephrine (1 microM), with increasing response over successive 24-h treatment periods. Two molecules Mr approximately 30 and 32 kDa appeared to be the predominant dimeric forms of inhibin secreted by the cells, while 26 kDa activin was present in excess over inhibin. Large amounts of 40-44 kDa protein were detected by the alpha-directed antisera only, which may be a form of the inhibin alpha-subunit precursor protein. Secretion of activin was responsive to phorbol ester-mediated stimulation but not to the presence of GnRH or elevated cAMP concentrations. The divergence in maternal serum inhibin and hCG concentrations during late pregnancy remains unexplained by these findings. PMID- 7886023 TI - Cytotoxicity of tumour necrosis factor-alpha and gamma-interferon against primary human placental trophoblasts. AB - Tumour necrosis factor-alpha (TNF-alpha) and gamma interferon (IFN-gamma) are expressed within human placental villi during normal pregnancy, yet their functions remain unknown. Since villous cytotrophoblasts are within the paracrine reach of this expression, the effects of TNF-alpha and IFN-gamma on a purified population of term placental cytotrophoblasts were examined. After 4 days of culture TNF-alpha alone induced a loss of trophoblast viability as measured by both metabolic capacity (MTT reduction) and DNA content. The combination of TNF alpha and IFN-gamma enhanced the damaging effect. Neutralizing antibodies against TNF receptor p55, but not p75, partially reversed the TNF-alpha-induced cytotoxicity. After 24 h of culture, TNF-alpha and IFN-gamma increased the fraction trophoblasts containing nicked DNA, and after 60 h, increased the detachment of cells characterized by a distorted morphology, lower DNA content, and fragmented DNA. These results suggest that a physiological role of TNF-alpha and IFN-gamma expression in the placental villi may be to regulate the apoptotic death of villous cytotrophoblasts. The studies also predict potential harmful effects on placental development and function following aberrant inflammatory cytokine expression triggered by intravillous infections. PMID- 7886024 TI - Quantitative evidence for the spatial dispersal of trophoblast nuclei in human placental villi during gestation. AB - A common assertion in the literature is that Langhans cells in placental villi decline in number during gestation but this is a misinterpretation which may be caused by the greater growth of villous surface area compared with trophoblast volume. To test this possibility, human placentae were collected at 12-41 weeks of gestation for a cross-sectional study on the packing density of nuclei within villous trophoblast. Numbers of nuclei in the cyto- and syncytiotrophoblast were estimated using a design-based stereological device, the physical disector (parallel pairs of sections). Surface areas were estimated in order to assess the overall growth of villous arborizations. Packing densities of nuclei were calculated and expressed as numbers/1000 microns 2 of villous surface. Densities decreased during gestation and this can be explained by expansion of villous surface area and thinning of trophoblast. The biggest drop in packing density of cytotrophoblast nuclei (30 per cent) occurred between 17-21 and 22-26 weeks and this period coincided with the largest changes in villous surface area (62 per cent increase) and trophoblast thickness (30 per cent decrease). Results are consistent with the notion of an epithelial proliferative unit of constant volume and comprising about nine syncytiotrophoblast nuclei per Langhans cell. PMID- 7886026 TI - Release of lipid from the equine placenta during in vitro incubation. AB - An in vitro incubation technique was used to examine release of lipids from the equine placenta. Placental tissue was obtained at term (n = 5, term = 320-365 days) and earlier in gestation (n = 8, mean = 266 days). Term placentae were incubated at two temperatures, 4 degrees C (control) and 37 degrees C for 2 h. Pre-term placentae were incubated at 37 degrees C with two different concentrations of fatty acid in the medium. Tissues and media were analysed for their lipid concentrations. Term and pre-term placentae released free fatty acid (FFA) and phospholipid into the incubation medium during incubation at 37 degrees C. Long chain polyunsaturated fatty acids derived from the essential fatty acids were released into the media. The fatty acid profiles of the lipids released during incubation more closely resembled those of fetal plasma than maternal plasma lipids as measured in previous studies. These data are consistent with the view that the equine placenta is a source of both FFA and phospholipid for the fetus and that the placenta may provide long chain polyunsaturated fatty acids for the fetal foal. PMID- 7886025 TI - Reduced thromboxane receptor affinity and vasoconstrictor responses in placentae from diabetic pregnancies. AB - Thromboxane has been implicated in the pathogenesis of maternal hypertension in high-risk pregnancies, but potential abnormalities in thromboxane-mediated constriction of fetoplacental vessels has not been examined. Using the isolated perfused fetoplacental cotyledon, we compared the vasoconstrictor responses to a thromboxane mimetic, U46619, in placentae from normal women and women with diabetes mellitus (classes C, D and R). Increases in perfusion pressure in response to bolus injections of U46619 were used to construct dose-response curves. The threshold dose of U46619 to cause a pressor response was similar in placentae from normal and diabetic pregnancies, but the slope of the dose response curve was decreased by 39 per cent in placentae from diabetic pregnancies compared with normal controls (P < 0.01). To examine the potential contribution of altered thromboxane receptors, equilibrium binding studies were performed using the thromboxane antagonist [3H]-SQ29548 to a 44,000 g fraction of placental homogenate. The affinity of thromboxane receptors was significantly decreased in placentae from diabetic pregnancies compared with normal controls [Kd = 41.9 +/- 7.9, (n = 6) versus control, 21.4 +/- 1.3 nM (n = 26), P < 0.001]. In contrast, the density of thromboxane receptor sites was not significantly changed (diabetes, 176.0 +/- 6.2 versus control, 150.3 +/- 6.5 fmol/mg, P = not significant). Placental production of thromboxane and prostacyclin were measured by the incorporation of [14C]-arachidonic acid into [14C]-thromboxane B2 and [14C]-6-keto-prostaglandin F1 alpha, respectively. Incorporation of [14C] arachidonic acid into both thromboxane B2 and 6-keto-prostaglandin F1 alpha was similar in placentae from diabetic and normal pregnancies. We conclude that vascular responsiveness to thromboxane is reduced in placentae from mothers with diabetes by a receptor-mediated mechanism. These changes may contribute to abnormalities in the regulation of fetoplacental haemodynamics, growth and development in pregnancies complicated by diabetes mellitus. PMID- 7886027 TI - Placental arsenic and cadmium in relation to lipid peroxides and glutathione levels in maternal-infant pairs from a copper smelter area. AB - Arsenic exposure may enhance oxidative damage causing adverse health effects in pregnant women. The purposes of this paper are: (i) to evaluate placental arsenic concentration as a biomarker of arsenic exposure for pregnant women; and (ii) to examine the relationship between metal exposure from a copper smelter area in Bulgaria and oxidative damage during pregnancy (as measured by glutathione and lipid peroxides) in 49 maternal-infant pairs. Placental levels of arsenic were highest in areas with the highest environmental contamination, and environmental variables (residency, smoking and occupational exposure) explained a large portion of the observed variability in placental arsenic levels (linear regression R2 = 0.71). The combined exposures of smoking and living in the smelter area were associated with lower glutathione antioxidant protection. The per cent maternal and cord blood glutathione in reduced form was significantly lower for smokers compared to non-smokers in the smelter area (47 versus 66 per cent in maternal blood, P < 0.01, and 60 versus 75 per cent in cord blood, P < 0.05). Higher concentrations of lipid peroxides in maternal blood, cord blood and placenta, though not statistically significant, suggested that pregnant women with both exposures may be at higher risk of oxidative damage. PMID- 7886028 TI - The placental transfer and toxicity of selenite relative to cadmium in the human term perfused placenta. AB - Selenite and cadmium both cause reproductive effects in animals. Cadmium is an acute placental toxicant, with apparent limited transfer to the fetus. This study examines the placental transfer of selenite, and the hypothesis that similar to cadmium, selenite may also be a direct placental toxicant. Using dual perfusion of the human term placental lobule, both non-protein bound (< 776 Da) selenite and cadmium equilibrated across the placenta within 4 h. The transfer of selenium, added as selenite, was not limited at concentrations from 2-40 nmol/ml. At initial maternal concentrations of 20 nmol/ml, selenium attained higher concentrations in the fetal perfusate compared with cadmium concentrations. Protein binding of cadmium in perfusates (45 per cent at 30 min) and placental cytosol (approx. 87 per cent) was greater than selenium (perfusate, 7 per cent at 30 min, cytosol, 50-60 per cent), which may partially account for the differences in placental transfer. Cadmium (20 nmol/ml) produced adverse effects on the production and release of human chorionic gonadotropin (hCG) in 4 h. No adverse effects were noted during 4 h exposures to selenite at initial concentrations of up to 40 nmol/ml. Thus, unlike cadmium, in which placental accumulation and direct placental toxicity contributed to acute reproductive effects, selenite at concentrations up to 40 nmol/ml was not a direct toxicant under these perfusion conditions. PMID- 7886029 TI - Hepatotrophic activity in mouse serum infected with plerocercoids of Spirometra erinacei. AB - To investigate the mechanism by which liver weight increases during plerocercoid infections as well as the possible existence of a hepatocyte-growth-factor (HGF) like substance in the serum of mice infected with Spirometra erinacei plerocercoids, liver DNA synthesis was measured in vivo and in vitro. Infection with S. erinacei plerocercoids significantly stimulated DNA synthesis in mouse parenchymal hepatocytes prior to the increase in liver weight, at least partly by stimulating the induction of the salvage pathways of pyrimidine biosynthesis. Furthermore, infected mouse serum directly stimulated DNA synthesis in cultured mouse parenchymal hepatocytes. These results suggest that an HGF-like substance is present in the serum of mice infected with S. erinacei plerocercoids. PMID- 7886030 TI - Characteristics of naturally acquired avian malaria infections in naive juvenile African black-footed penguins (Spheniscus demersus). AB - Antibody responses to naturally acquired Plasmodium relictum and P. elongatum infections, blood parasitemia, and disease signs were investigated in 23 naive juvenile African black-footed penguins (Spheniscus demersus). Anti-Plasmodium spp. immunoglobulins were detected by enzyme-linked immunosorbent assay (ELISA) using P. falciparum antigens. All birds rapidly developed antibody to P. relictum and P. elongatum. Five penguins showed detectable parasitemia and signs of the disease. Parasitemia was not related to the timing of the maximal antibody response or to the antibody titer. Two of the five parasitemic birds died and gross examination revealed splenomegaly, hepatomegaly, and congested, edematous lungs. Although the other 17 birds were clearly exposed to the disease, none showed signs of infection. No subsequent episode of parasitemia was observed in individual penguins. A comparison of the fate of 1993 penguins with those from other years showed a great variability in the proportion of birds exhibiting signs of malaria. PMID- 7886031 TI - Immunoglobulin G2a isotype may have a protective role in Plasmodium berghei NK65 infection in immunised mice. AB - All CBA mice that had been immunised by means of four successive inoculations of Plasmodium berghei NK65, each inoculation being followed by chemotherapy, survived an intravenous challenge inoculation of parasite, with 4/12 mice developing patent parasitaemia that resolved within 2 weeks. In contrast, all non immunised control mice died before the 10th day post-challenge. Examination of sera for antibodies revealed that the immunised mice, all of which survived the challenge, had significantly high anti-plasmodial whole IgG, IgG1, and IgG2a titres before the challenge. A 16-fold rise in IgG2a titre alone was recorded on the 5th day post-challenge, with a further boosting of the titre to 4096 being observed on day 10. In comparison, the titres of Ig isotypes in the non-immunised control mice that succumbed to the challenge remained below 4. Specific IgG subclasses, in particular IgG2a, could be involved in the humoral immune protection against this rodent parasite. PMID- 7886032 TI - Prevalence of antibodies against Toxoplasma gondii in pigs in Austria--an evaluation of data from 1982 and 1992. AB - To obtain information on the prevalence of antibodies against Toxoplasma gondii in pigs in Austria, 4697 blood samples from pigs were collected in the years 1982 and 1992 and tested by an indirect fluorescence antibody test. The results of the studies show that due to modern fattening systems the prevalence of infections with T. gondii in slaughtered pigs has obviously decreased in Austria during the last 10 years. The investigations indicate a significant difference in the rate of infection of pigs between 1982 (13.7%) and 1992 (0.9%). Additionally, the prevalence of T. gondii antibodies in breeding sows (1982, 43.4%; 1992, 4.3%) was higher than that in fattening pigs (1982, 12.2%; 1992, 0.8%). PMID- 7886033 TI - Experimental transmission of Babesia microti infection by the oral route. AB - Previously we have described the transmission of malaria by the oral route in a murine model. Due to the similarities between Plasmodium and Babesia, we tried to reproduce oral transmission in parasites of the latter genus by ingestion of infected blood and by cannibalism. In the first case, experimental mice were inoculated orally with 20, 50, or 100 microliters of Babesia microti-infected blood, and in the second, each fasted experimental mouse was offered the corpse of an infected mouse serving as the bait inoculum. B. microti infection was acquired by 3.7% of all experimental animals orally inoculated with infected blood and by 15.1% of all mice inoculated by cannibalism. The approximate period of prepatency ran from 2 to 4 weeks. No control mouse acquired the infection. This represents the first time that oral transmission of babesiosis has been described. This kind of transmission may be present in nature. Babesiosis may be acquired and maintained in nature in the absence of ticks. PMID- 7886034 TI - Development and distribution of bovine trichostrongyle infective larvae on a pasture irrigated by flooding or by spraying. AB - To compare the ecological effects of irrigation of a pasture, by flooding or by spraying, on the gastro-intestinal parasites of calves, two contiguous plots, one flooded and the other sprayed, were grazed for 10 days by naturally infected animals. Faeces, grass and soil under pats were sampled for 17-20 weeks for larval counts. The experiment was performed once in the spring and once in the summer. In the spring the maximal development rates in sprayed and flooded plots were 7.8 and 12.6 stage 3 larvae (L3)/100 eggs, respectively, for Cooperia and 3.5 and 3.2 L3/100 eggs, respectively for Ostertagia. During the summer, development rates were less than 1%. The main differences were found in the vertical distribution of the larvae: spraying favoured migration on grass and flooding favoured migration in soil, this finding being similar for both genera. The spatial distribution, studied by dividing each plot into 18 subplots, was a little more regular on grass in the sprayed plot. We conclude that the infection risk for calves is lower in flooded pasture than in sprayed pasture. PMID- 7886035 TI - Serodiagnosis and seroepidemiology of human unilocular hydatidosis in Jordan. AB - A total of 2182 serum samples from 38 patients with surgically confirmed unilocular hydatidosis, 19 clinically assessed patients, 15 patients with parasitic infections other than hydatidosis, 104 hospital outpatients, and 2006 normal Jordanians were serodiagnosed for the presence of IgG antibodies against hydatid fluid, circulating immune complexes (CIC), and/or hydatid circulating antigen (CA). Anti-hydatid IgG antibodies were detected in the sera of 77.4% of patients with hydatid disease and persist for very long periods postsurgery. As many as 54.1% of patients with hydatidosis had positive levels of CIC, and 16.1% had circulating antigen in their sera. The search for circulating antigen and CIC decreased the number of false-negative hydatid cases from seven to three, and the combined sensitivity of the assays thus increased from 77.4% to 90.3%. Using the immunoblot technique, 16- and < 14.4-kDa Echinococcus granulosus-specific bands were detected in sera from 54.1% and 61.5% of patients with hydatid disease who were tested before and after surgery, respectively. The seropositivity rate for anti-hydatid IgG antibodies was 2.4% for the general Jordanian population and 5.8% for hospital outpatients. PMID- 7886036 TI - The phylogenetic position of Dimastigella trypaniformis within the parasitic kinetoplastids. AB - The nuclear 16S-like rRNA coding regions of two strains of the kinetoplastid flagellate Dimastigella trypaniformis Sandon (strain Ulm and strain Glasgow) were sequenced and phylogenetically analyzed. Strain Ulm was isolated from the hindgut contents of the Australian termite Mastotermes darwiniensis Frogatt, whereas strain Glasgow originates from a soil sample in Scotland. After preparation of genomic DNA the 16S-like rRNA coding regions were amplified using polymerase chain reaction (PCR) technology. The amplification products were cloned in a plasmid vector and sequenced according to standard methods. The sequence of the 16S-like rRNA coding region of strain Ulm differs less than 2% from the sequence of strain Glasgow, indicating that the two strains are most probably members of one species. Phylogenetic analysis of the sequence data positioned D. trypaniformis Sandon as a deep branching lineage near the root of the kinetoplastid group of flagellates. PMID- 7886037 TI - A cysteine proteinase in the cercariae of Diplostomum pseudospathaceum (Trematoda, Diplostomatidae). AB - A cysteine proteinase was detected in extracts from cercariae of the trematode Diplostomum pseudospathaceum. The enzyme preferred protein substrates over synthetic, chromogenic peptides. The optimal pH for hydrolysis of substrates was 7.2 for azocoll, 6.4 and 7.6 for azocasein, 7.6 for azoalbumin, and 6.8 for N benzoyl-L-arginine-4-nitroanilide. Elastin-Congo red and certain N-blocked L aminoacyl- and L-peptidyl nitroanilides bearing L-phenylalanine, L-alanine, L tyrosine, and L-leucine at the P1 subsite were not hydrolyzed. Thiol-reducing and divalent cation-complexing agents stimulated the proteinase activity, whereas thiol-blocking agents inhibited it. The relative molecular weight of the enzyme was approximately 40,000 as determined by SDS-PAGE. Detection of an identical proteinase in water after treatment of living cercariae with praziquantel suggests that the enzyme occupied the penetration glands in the larvae. Thus, when secreted by the parasite during invasion of an appropriate host, the enzyme might act as a penetration-promoting factor. PMID- 7886038 TI - Histochemistry of proteinases in the cercariae of Diplostomum pseudospathaceum (Trematoda, Diplostomatidae). AB - Two distinct endopeptidases were detected histochemically in the cercariae of Diplostomum pseudospathaceum: a serine proteinase occupying the ceca and a cysteine proteinase occupying the penetration glands. The former was relatively resistant to formaldehyde, required either Ca2+ or Mg2+ for its stability, and was sensitive to organic fluorophosphate inhibitors but insensitive to thiol blocking agents. The latter enzyme required both reducing and divalent cation complexing agents for its full activity and was sensitive to formaldehyde, thiol blocking agents, and diazonium salts. Both enzymes hydrolyzed a number of N blocked L-aminoacyl-, and N-blocked L-peptidyl-naphthylamides bearing L-arginine at the P1 subsite. The pH optima for hydrolysis of the substrates were 8.0 for the serine proteinase and 7.6 for the cysteine proteinase. PMID- 7886039 TI - Trypanosoma brucei is protected from the cytostatic effects of nitric oxide under in vivo conditions. AB - In mice infected with Trypanosoma brucei, splenic and peritoneal macrophages release substantial amounts of nitric oxide (NO). The production of NO by activated macrophages has been reported to be a nonspecific immune-effector mechanism against several parasites, and in this work we investigate the role of NO in killing T. brucei. Addition of bloodstream trypanosomes to peritoneal macrophages activated in vitro resulted in an NO-dependent inhibition of parasite growth. This effect was totally abrogated when dilutions of whole blood were included in the cultures, suggesting that bloodstream parasites such as T. brucei are not susceptible to NO-mediated killing in vivo. PMID- 7886040 TI - The behavior and pathogenicity of Toxacara canis larvae in mice of different strains. AB - In the present study the behavior and pathogenicity of second-stage larvae of Toxocara canis were examined in different mouse strains with special emphasis on the major histocompatibility complex (MHC). Mice of the inbred strains BALB, C3H, C57BL, and DBA and the outbred strain NMRI were infected orally with 1000 second stage larvae of T. canis. The clinical behavior of the animals; the numbers of larvae detected in the liver, lungs, brain, and musculature; the hematological and serological parameters; and histological sections were examined. In mice of the BALB strain, no death occurred during the entire period of the investigation and the pattern of body-weight development of infected and uninfected animals was almost identical. The highest larval counts in the brain of all strains were found in BALB mice. The percentage of eosinophils in the blood of BALB mice increased after the 8th week postinfection, whereas it decreased in the other strains. Histological and pathophysiological changes developed to a lesser extent in this strain than in the other strains. In mice of the strains C3H, C57BL, DBA, and NMRI, deaths occurred from the 4th week postinfection onward. The infected animals lost weight in comparison with the uninfected controls; the number of larvae found in the brains of infected mice of the above-mentioned strains were lower than those detected in the BALB strain. There is no evidence that mechanical damage caused by migrating larvae in the brain tissue is mainly responsible for symptoms of central nervous toxocariasis. Likewise, the assumption that the MHC is involved in the allergic-inflammatory response in the brain could not be proven: infected mice of the BALB and DBA strains reacted completely differently, although both are equipped with the same MHC haplotype. PMID- 7886041 TI - Leishmania mexicana: the influence of slightly elevated temperature on the ultrastructure of axenic amastigote-like forms. PMID- 7886043 TI - Identification of a cDNA clone from the larval stage of Echinococcus granulosus with homologies to the E. multilocularis antigen EM10-expressing cDNA clone. PMID- 7886042 TI - Onchocerca volvulus and Acanthocheilonema viteae: cloning of cDNAs for muscle cell intermediate filaments. PMID- 7886044 TI - The invasion of the rabbit intestinal tract by Eimeria intestinalis sporozoites. AB - To follow the route of migration of Eimeria intestinalis sporozoites from the excystation stage to their development in the epithelial cells of the ileum, we inoculated sporocysts into the duodenum of coccidia-free rabbits and euthanized the animals at 10 min to 12 h post-inoculation. Excystation occurred at less than 10 min after the experimental infection. The sporozoites penetrated into the epithelium of the duodenum at as early as 10 min post-inoculation; 6 h later, the number of sporozoites had dramatically decreased in the duodenal mucosa, with a corresponding increase being noted in the ileal mucosa. These findings suggest that sporozoites invade the duodenal epithelium and migrate to the ileum by an as yet unknown nonlumenal tissue route. PMID- 7886045 TI - Contribution of N,N'-dialkylbenzamide groups to trypanocidal properties of spiroarsoranes. PMID- 7886046 TI - Peptide utilization by tissues: current status and applications of stable isotope procedures. PMID- 7886047 TI - Access methods in nutritional support. PMID- 7886048 TI - Nutritional support via percutaneous endoscopic gastrostomy. PMID- 7886049 TI - Control of seasonality by melatonin. PMID- 7886050 TI - Photoperiod and the regulation of annual and circannual cycles of food intake. PMID- 7886051 TI - Seasonal changes in growth and energy status in the Third World. PMID- 7886052 TI - Seasonal changes in body mass, body composition and food requirements in wild migratory birds. PMID- 7886053 TI - Seasonal variation in vitamin D. PMID- 7886054 TI - Seasonal infections and nutritional status. PMID- 7886055 TI - beta-Carotene, are we misreading the signals in risk groups? Some analogies with vitamin C. PMID- 7886056 TI - Newer aspects of micronutrients in chronic disease: vitamin E. PMID- 7886057 TI - Newer aspects of micronutrients in chronic disease: copper. AB - Cu ions are pro-oxidants when added to biological material in vitro and excessive levels of Cu in the body, such as in Wilson's Disease (Yarze et al. 1992) promote oxidant-related pathologies. In contrast there is now substantial evidence that an optimum level of Cu is required to maintain antioxidant defence and that Cu deficiency in animals increases oxidant stress. There are abundant mechanistic relationships linking Cu deficiency and processes associated with IHD, some of which do not directly involve oxidant damage. These mechanistic relationships, however, have mostly been demonstrated in animal models and more information is urgently required concerning possible chronic mild Cu deficiencies in human populations. A major hurdle to advances in this area is the lack of indices of Cu status which are sensitive enough to detect marginal Cu deficiency in humans. The question, therefore, of whether or not there is a role for mild Cu deficiency in the onset of chronic disease processes, including IHD, remains unanswered. PMID- 7886058 TI - Iron, magnesium and ischaemic heart disease. PMID- 7886059 TI - Micronutrients and cancer aetiology: the epidemiological evidence. AB - Micronutrient deficiencies occur most commonly in poor countries and, therefore, are most likely to be associated with cancers common in these countries. Epidemiological studies are hampered by inaccurate measurement of micronutrient intake and by the correlations between intakes of many nutrients. The strongest evidence for a protective effect of micronutrients is for oesophageal cancer. The identity of the micronutrients is not certain, but may include retinol, riboflavin, ascorbic acid and Zn; alcohol, smoking and dietary nitrosamines increase the risk for oesophageal cancer. For stomach cancer there is good evidence that fruit and vegetables are protective. The protective effect of these foods might be largely due to ascorbic acid, but other nutrients and non nutrients may also be important; the risk for stomach cancer is increased by salt, some types of preserved foods, and by infection of the stomach with the bacterium Helicobacter pylori. The risk for lung cancer appears to be reduced by a high intake of fruit and vegetables, but it is not clear which agents are responsible and the major cause of lung cancer is cigarette smoking. Diet is probably the major determinant of the risk for colo-rectal cancer; there is evidence that fruit and vegetables and fibre reduce risk and that meat and animal fat increase risk, but there is no convincing evidence that these relationships are mediated by micronutrients. The risk for cervical cancer is inversely related to fruit and vegetable consumption and, therefore, to consumption of carotenoids and ascorbic acid, but the major cause of this cancer is human papillomavirus and it is not yet clear whether the dietary associations indicate a true protective effect or whether they are due to confounding by other variables. The evidence that micronutrients are important in the aetiology of either breast cancer or prostate cancer is weak, but the possible roles of 1,25-dihydroxycholecalciferol and alpha-tocopherol in prostate cancer require further study. PMID- 7886060 TI - New metabolic roles for selenium. PMID- 7886061 TI - Novel functions of vitamin B6. PMID- 7886062 TI - The role of folate in the prevention of neural-tube defects. PMID- 7886063 TI - Genotype-environment interactions and the estimation of the genomic mutation rate in Drosophila melanogaster. AB - We have studied the relative fitnesses of three genotypes of Drosophila melanogaster in 50 environments. Two genotypes, the MA lines, had accumulated mutations in the absence of natural selection over 62 generations. The third was a related strain where selection had continued to act. The environments differed in three factors: parental density, dilution of the medium, and the temperature regime and medium composition. Our measure of fitness assessed fecundity and viability relative to a reference genotype. Both MA lines always had lower fitnesses than the selected line, but the difference increased dramatically with dilution of the medium and, especially, crowding. Under the most severe conditions, the performance of the MA lines approached 0. This increased difference in harsh conditions may be caused both by a uniform increase in the magnitude of deleterious effects of all mutations and by the exposure of mutations which are essentially neutral under benign conditions. If the second cause is important, previous experiments are likely to have underestimated the genomic deleterious mutation rate in Drosophila melanogaster more than previously thought. PMID- 7886064 TI - Osmo-dependent Cl- currents activated by cyclic AMP in follicle-enclosed Xenopus oocytes. AB - The role of adenosine 3',5'-cyclic monophosphate (cAMP) in generating the osmo dependent slow inward membrane currents (S(in)) elicited by activation of follicle stimulating hormone (FSH) or acetylcholine (ACh) receptors was studied in voltage-clamped, follicle-enclosed oocytes of Xenopus laevis (follicles). Forskolin (FSK) also generated S(in) currents, and in low concentrations it potentiated the S(in) currents elicited by FSH but not those elicited by ACh. Moreover, intra-oocyte injections of cAMP elicited similar slow inward currents (cAMP-S(in)) that: (i) were carried mainly by chloride ions; (ii) were abolished by defolliculating the oocytes; and (iii) were dependent on the osmolarity of the external medium. Compared with the Ca(2+)-dependent chloride channels that are located in the oocyte membrane; the cAMP-activated S(in) channels were less permeable to I- and Br-, and their current-voltage relation did not rectify strongly at negative potentials. Generation of cAMP-S(in) desensitized the FSH S(in) currents, but did not have effects on both the S(in) and the fast chloride current (F(in)) specifically elicited by ACh. Furthermore, follicular phospholipase C activation through stimulation of angiotensin II (AII) receptors failed to generate the current responses elicited by ACh. We conclude that cAMP acts as a potent second messenger in generating the osmo-dependent Cl- currents elicited by FSH but not those elicited by ACh. The mechanisms underlying the ACh responses remain unknown. The osmo-dependent chloride channels activated by cAMP may play a role in the control of volume of the follicular cells-oocyte complex. PMID- 7886065 TI - Axon contact is associated with modified expression of functional potassium channels in mouse Schwann cells. AB - In organotypic cultures of mouse dorsal root ganglia, Schwann cells were classed as isolated, that is to say without contact with neurites, or as attached to neurites. It was known that isolated Schwann cells in these cultures display two types of voltage-dependent K+ currents, a fast transient current and a delayed sustained current. In this study, we have investigated outward K+ currents on Schwann cells attached to neurites. These all had a sustained current whose amplitude, timecourse, outward rectification, cumulative inactivation and sensitivity to tetraethylammonium were similar to those of the sustained current on isolated cells. However, the attached cells differed from the isolated cells in that only 15% had a detectable transient current. We suggest three possible explanations for this result: (i) that only cells with reduced transient K+ current move to contact the axon; (ii) that functional expression of these channels is down-regulated by close association with the axon; or (iii) that the channels are lost by transfer to the axon. PMID- 7886066 TI - Insights into the different exploits of colour in the visual cortex. AB - A new method that allows controlled masking of luminance contrast has been developed to study the use of chromatic signals in human vision. The method also makes it possible to examine the different uses of chromatic signals (e.g. the generation of perceived colour, or the construction and representation of object structure and form). By using this technique, we studied the threshold detection of chromatic signals in normal trichromats. The results show that chromatic signals are virtually unaffected by ongoing, randomly varying, luminance contrast changes. These findings suggest that chromatic signals are either processed independently or can be separated completely from any confounding luminance contrast components in the stimulus. Thresholds for detection of colour changes only, and for extraction of stimulus structure from chromatic signals in normal trichromats, in subjects with single cone receptor deficiency (i.e. dichromats) and in three subjects with abnormal colour vision caused by bilateral damage to ventromedial, extra-striate visual cortex (i.e. subjects with cerebral achromatopsia) have also been measured. No significant difference in thresholds for the two conditions was observed either in normal trichromats or in dichromats. Subjects with cerebral achromatopsia, however, reveal markedly different thresholds. The results suggest that chromatic signals are processed independently to generate perceived object colour or to construct spatially structured objects, and that these functions involve different neural substrates. The results help to explain, at least in part, why cerebral achromatopsia is a heterogeneous disorder, and why there can be significant differences in the effective use of chromatic signals in subjects described as cerebral achromatopsics. PMID- 7886067 TI - Cocaine-induced conditioned place approach in rats: the role of dose and route of administration. AB - The hedonic valence of the interoceptive stimuli associated with a wide range of cocaine doses administered by either SC or intraperitoneal injections was assessed in rats. Ninety-six male Sprague-Dawley rats were randomly assigned to different dose- and route-of-administration dependent groups (n = 8/group) and conditioned in a place learning task. During half of the conditioning trials, rats received either SC or intraperitoneal injections of saline or an individual dose of cocaine from 0.32 to 32 mg/kg (10 groups, 0.5 log common log unit increments), and were immediately placed in the initially nonpreferred compartment of a straight alley-way place-conditioning chamber. Prior to the other conditioning trials, rats received equivalent volumes of saline injections via the same routes of administration and were immediately placed in the initially preferred compartment. Two additional control groups received saline injections on both sides. Each rat received eight conditioning trials (four on each side). Significant conditioned place approach was produced by both SC- and IP-injected cocaine. However, the IP route of cocaine administration required a dose of 10 mg/kg cocaine to elicit a conditioned place approach, whereas a 0.32 mg/kg SC cocaine injection produced a CPP. Saline injections alone did not change the initial preference scores, and conditioned place aversions were not produced by any cocaine dose. The results of the present study demonstrate the relative safety of SC cocaine administration in the rat and a behavioral potency difference between these two routes of administration relative to the hedonic valence of the associated subjective states. PMID- 7886068 TI - Technical report: the subcutaneous administration of cocaine in the rat. AB - Eight male Sprague-Dawley rats were treated with 32 mg/kg cocaine, twice daily, for 2 weeks using a SC route of administration. Using a cocaine stock solution of 1.2-1.6 mg of cocaine hydrochloride per ml of sterile saline, we demonstrate, for the first time, the relative safety of subcutaneously administered cocaine in the rat. There was absolutely no evidence for focal dermal necrosis, in any rat, after the 2-week chronic period. PMID- 7886069 TI - Opiate effects on isolation stress in domestic fowl. AB - In an attempt to examine the role of opioid system functioning in social attachment and isolation stress in young domestic fowl, the effects of morphine (5.0 mg/kg) and naloxone (5.0 mg/kg) were evaluated on distress vocalizations, thermal nociception, thermoregulation, and respiration following 15 min of isolation in 7-day-old White-Leghorn cockerels. Morphine decreased and naloxone increased distress vocalizations in isolated chicks. Isolation produced an increase in jump response latencies (i.e., hypoalgesia) on a standard hot-plate test. In general, morphine decreased and naloxone increased mean jump latencies in both isolated and nonisolated chicks. Isolation produced an increase in core body temperature (i.e., hyperthermia); morphine decreased and naloxone increased core body temperatures independent of the isolation manipulation. Social isolation did not affect respiration. However, morphine depressed respiration in both isolated and nonisolated chicks. These results support the notion that opioid systems modulate social attachment and isolation stress. PMID- 7886070 TI - A comparison of the antinociceptive effects of opioid agonists in neonatal and adult rats in phasic and tonic nociceptive tests. AB - Changes in the attitudes about neonatal pain and pain management have recently resulted in increases in the administration of opioids to neonates. Little is known, however, about the relative potencies of the various opioid agonists employed, especially in comparison to adult responses. The first objective in the present study was to compare the antinociceptive potency of four clinically relevant opioids in neonatal and adult rats. The second objective was to compare and contrast these agents in two different types of nociceptive tests: tonic (formalin-induced inflammation) and phasic (tail flick and hot plate). Our results indicate that the opioid agonists morphine, meperidine, and fentanyl, and the mixed agonist buprenorphine were all effective antinociceptive agents in both neonates and adults in each of the three tests employed, and that the relative potencies of these agents appeared to be similar in neonates and adults. In general, the pups were more sensitive to the antinociceptive agents when tested in the phasic nociceptive tests, and the drugs were more potent in the tonic test than either of the phasic tests. PMID- 7886071 TI - Clozapine's effects on phencyclidine-induced disruption of prepulse inhibition of the acoustic startle response. AB - The reduction in magnitude of the startle reflex in response to a loud noise produced by prior presentation of a stimulus of lower intensity is known as prepulse inhibition (PPI). PPI may be disrupted by a variety of drugs, most notably by dopaminergic agonists such as apomorphine and by phencyclidine (PCP), and related noncompetitive N-methyl-D-aspartate (NMDA) antagonists. Apomorphine induced disruption of PPI is antagonized by both typical and atypical neuroleptics. The present study examined the effects of the atypical neuroleptic, clozapine, alone and in combination with PCP, on PPI in rats. The results of previous studies suggest that disruption of PPI by PCP and similar drugs is not sensitive to antagonism by typical neuroleptics such as haloperidol. The results of the present study show that clozapine's effect on PCP-induced disruption of PPI is also limited. The failure of clinically effective antipsychotics of diverse chemical classes to block the effects of PCP on PPI of acoustic startle suggest that the effects of PCP in this procedure may represent a model of attentional deficits observed in treatment-resistant schizophrenia. PMID- 7886072 TI - Route of morphine administration modulates conditioned analgesic tolerance and hyperalgesia. AB - The present experiments investigated the effects of route of drug injection on two of the phenomena associated with repeated, cued, morphine administration. Experiment 1 examined the degree of situational specificity of analgesic tolerance following 5 days of morphine (5 mg/kg) delivered either subcutaneously (SC) or intravenously (i.v.). Situationally specific tolerance was only observed following i.v. morphine, although nonspecific tolerance was evident in both instances. Experiment 2 indicated that this difference was not due to dose, as neither 2.5 or 7.5 mg/kg SC morphine produced demonstrable situationally specific tolerance. Experiment 3 examined the putative existence of compensatory responses underlying the observed tolerance. Hyperalgesia in response to the environment in which morphine was experienced was evident in animals trained with i.v. morphine, but not in those receiving repeated SC injections. Potential explanations for these effects of route of administration are discussed. PMID- 7886073 TI - Age-dependent effects of NGF and scopolamine on suckling behavior of neonatal mice. AB - Nerve growth factor (NGF) influences the neurochemical differentiation of central cholinergic neurons of developing rodents. In this study, NGF was given intracerebrally to mice on different postnatal days (days 5 and 7, or days 8 and 10). Pups were tested for suckling behavior 24 h after the second NGF injection, following systemic administration of either the muscarinic cholinergic antagonist scopolamine or saline solution. Scopolamine significantly impaired nipple attachment on day 11 but not on day 8, and decreased locomotor activity in 11-day pups. NGF given on days 5 and 7 increased paddling and treading on day 8, and this effect was more pronounced in scopolamine injected pups. Pretreatment with NGF on days 8 and 10 decreased activity levels in 11-day pups. The differences in the effects of scopolamine at successive ages suggest that distinct portions of the cholinergic system mature at different rates and that sensitivity to NGF is age dependent. NGF appears to influence functional maturation of that portion of the cholinergic system involved in the regulation of locomotor activity. PMID- 7886074 TI - Tolerance to and dependence on MK-801 (dizocilpine) in rats. AB - Rats were trained to respond under a fixed-ratio 30 schedule for food presentation during four daily 0.5-h sessions occurring every 6 h. After stable baseline response was established, osmotic minipumps were implanted that infused vehicle or (+)-5 methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine hydrogen maleate (dizocilpine; MK-801), SC. Behavioral sessions continued to be conducted daily. After 10 days the infusion pumps were removed. Vehicle and 0.10 mg/kg per day MK-801 did not affect behavior during infusions or after cessation of dosing. Dosing with 0.32 and 0.56 mg/kg per day initially suppressed responding, but tolerance developed to these effects. After the infusions were stopped, a dose-dependent disruption of operant behavior occurred. Response rates for the 0.32 and 0.56 mg/kg per day infusion groups were suppressed to 41 and 27% of preinfusion control response rates, respectively, the day after dosing stopped; however, no physical signs of abstinence were observed. Response rates recovered toward control over the next 2-4 days. In a separate experiment, the suppression of response produced by abstinence from 0.32 mg/kg per day of MK-801 (SC) for 10.5 days was reversed by readministration of MK-801 (IP). These results demonstrate that MK-801 produces dependence, as evidenced by the emergence of a behavioral abstinence syndrome after cessation of dosing. PMID- 7886075 TI - Influence of exercise training and age on uncoupling protein mRNA expression in brown adipose tissue. AB - The ability to regulate body temperature diminishes with age. Exercise training is known to increase cardiovascular performance, and there is some evidence of a cross-adaptation between exercise and cold tolerance in young rats. The present study was designed to examine the effects of physical training by treadmill running on the capacity for brown adipose tissue (BAT) thermogenesis in young and old rats. To this end, we assessed BAT uncoupling protein (UCP) mRNA expression in sedentary and exercise-trained 5- and 25-mo-old F-344 rats. The amount of UCP mRNA, whether expressed as per unit RNA or per BAT, did not change with either age or training. These data indicate that there is no cross-adaptation by exercise on adaptive thermogenesis in BAT in either young or old rats. PMID- 7886076 TI - Ketamine: acquisition and retention of classically conditioned responses during treatment with large doses. AB - Two experiments were conducted in rabbits to examine the effects of ketamine (0, 100, and 200 mg/kg) on the acquisition and retention of the classically conditioned nictitating membrane response (NMR). Classical conditioning of the NMR was accomplished by pairing tone and light conditioned stimuli (CS) with paraorbital shock as the unconditioned stimulus (UCS). Experiment 1 assessed the effects of the drug on acquisition and retention of conditioned responses (CR) and determined the role of previous exposure to the experimental environment. Ketamine blocked the display of CR. However, data from subsequent retention testing under nondrug conditions revealed that rabbits that had previously received 100 mg/kg ketamine learned faster than saline-treated rabbits during the acquisition phases. Rabbits that received 100 mg/kg ketamine and were placed in the experimental chambers, but not presented with stimuli during the acquisition phase, did not learn faster during the retention phase than naive rabbits. Experiment 2 controlled further for the effects of nonassociative, unlearned processes. Control groups were presented with unpaired CS and UCS training after drug administration, and subsequently received conventional acquisition sessions under nondrug conditions. Their data indicated that the ketamine group's rapid acquisition during retention testing could not be attributed to nonassociative factors. We conclude that, although it was impossible directly to observe acquisition in rabbits under the influence of ketamine, it was possible that learning occurred as manifested by "savings" in subsequent learning trials. PMID- 7886077 TI - Cholinergic agents and delay-dependent performance in the rat. AB - We tested cholinergic agents in delayed matching and nonmatching to position. Each task had a delay between the presentation of information and the chance to act on it later. We used a titrating procedure, new to experiments with rats, to determine the delay. Linopirdine (0.1 mg/kg), which releases acetylcholine, and physostigmine (0.1 mg/kg), a cholinesterase inhibitor, ameliorated the impairment of accuracy produced by scopolamine hydrobromide (0.1 mg/kg). In some cases, scopolamine hydrobromide decreased the number of trials, but physostigmine and linopirdine did not ameliorate that impairment. Both the muscarinic receptor antagonist, scopolamine hydrobromide (0.1 and 0.3 mg/kg), and its peripherally acting analog, scopolamine methylbromide (0.1 and 0.3 mg/kg), decreased accuracy. The impairment produced by scopolamine methylbromide suggests that the deficit produced by muscarinic receptor antagonism may have both a central and peripheral component. At the highest dose, scopolamine hydrobromide decreased the number of trials completed. Thus, some of the effects of scopolamine hydrobromide involve nonmnemonic performance factors. The performance deficits produced by scopolamine hydrobromide suggest that it may be necessary to qualify drug effects in terms of their action on both memorial and nonmemorial aspects of performance. PMID- 7886078 TI - Linopirdine (DuP 996) improves performance in several tests of learning and memory by modulation of cholinergic neurotransmission. AB - The actions of linopirdine (DuP 996; 3,3-bis[4-pyrindinylmethyl]-1-phenylindolin 2-one) were evaluated in rats and mice in several cognitive behavioral tests, and for its effects on hippocampal acetylcholine (ACh) overflow in rats. Using mice treated with the muscarinic receptor antagonist, scopolamine, we studied the effects of linopirdine on retention of a passive avoidance task. Linopirdine (0.1 and 1 mg/kg) ameliorated the scopolamine-induced deficit, but at doses ranging from 0.01-1 mg/kg, it did not affect passive avoidance retention in normal (untreated) mice. In a scopolamine-induced hyperactivity test, linopirdine (1 mg/kg) decreased the motoric stimulation associated with the cholinergic hypofunction, without affecting locomotor activity on its own. Using rats, we studied the effects of linopirdine on performance in the Morris water maze spatial memory task. Young rats treated with atropine (30 mg/kg), a muscarinic receptor antagonist, took significantly longer to locate the submerged platform across 12 trials. Linopirdine (0.01 and 0.1, but not 1 mg/kg) ameliorated the atropine deficit. In addition, linopirdine (0.1 mg/kg) ameliorated the deficit in cognition-impaired aged rats (23-24 mo), but did not affect unimpaired aged rats. In terms of neurochemical action, linopirdine (1, 10, and 100 microM) produced a concentration-dependent increase in K(+)-evoked ACh overflow from superfused rat hippocampal slices. Also, linopirdine (10 microM) similarly increased ACh release in young control rats and cognition-impaired and nonimpaired aged rats. Our results confirm and extend findings from other studies that demonstrate the cognition-enhancing action of linopirdine in rodent models.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886079 TI - Mechanism of action of 8-OH-DPAT on learning and memory. AB - It has been previously demonstrated that pretraining injection of 8-hydroxy-2-(di n-propilamino)tetralin (8-OH-DPAT, a 5-HT1A agonist) impairs conditioned response (CR) in an autoshaping learning task. Therefore, in the present work we intended to determine whether such an effect could be prevented by pretraining, and whether pre- or postsynaptic 5-HT receptors are involved. Groups of rats received or did not receive food magazine training. On the next day, all groups in both conditions, pre- or posttraining, were treated with 8-OH-DPAT (0, 0.062, or 0.250 mg/kg). Posttraining groups were tested on a second session of autoshaping 24 h later. In a second experiment, naive rats received para-chlorophenylalanine (PCPA) (300 mg/kg x 3 days) before pre- or posttraining injection of 8-OH-DPAT. Results showed that in those groups trained to food magazine and treated 24 h later with 8-OH-DPAT, CR was not affected or enhanced. PCPA injection had no effect by itself, but blocked or attenuated the effect of a post- or pretraining injection of 8-OH-DPAT. The present data suggest that a) the pretraining effect of 8-OH-DPAT eliciting a decrease in CR can be eliminated by a food magazine training session; and b) presynaptic 5-HT1A receptors are involved in the effect of 8-OH-DPAT on the acquisition and consolidation of learning. PMID- 7886080 TI - Intracellular ionized calcium and increasing doses of lithium chloride therapy in healthy Sprague-Dawley rats. AB - The use of lithium salts in the prophylaxis and treatment of several psychiatric and neurologic disorders continues to be well accepted despite the apparent lack of understanding regarding its mode of action at the molecular level. This lack of delineation in the mechanism of action is supported by numerous conflicting publications. Despite the lack of understanding, a role for calcium in the manifestation of lithium's action is a constant singular consensus. Intracellular ionized calcium ([Ca2++]i) is involved in the proper functioning of cells because of its role in the second messenger pathway. It is therefore essential to evaluate the effect of lithium on intracellular calcium metabolism in a well defined system. In this study, platelets loaded with Fura-2-Acetoxymethyl were used to evaluate the effect of intraperitoneally administered lithium chloride at 0, 2.5, 5.0, 7.5, and 10 mmol/kg body wt. on [Ca++]i. The results showed a slight relative increase in serum Ca++ that correlated well with the dose of LiCl administered to the rats. The baseline [Ca++]i were comparable in the study groups, but the response to thrombin stimulation was more pronounced at LiCl doses of 2.5, 5.0, and 7.5/kg body wt. compared with control and rats treated with 10 mmol LiCl/kg body wt. This finding suggests a dose-dependent response of [Ca++]i to LiCl treatment. The observation may therefore explain the variations that have been reported in [Ca++]i studies with respect to LiCl therapy using different doses. PMID- 7886081 TI - Modulation of free intracellular calcium and cAMP by morphine and cannabinoids, alone and in combination in mouse brain and spinal cord synaptosomes. AB - Changes in [Ca++]i and cAMP were evaluated as possible mechanisms by which the cannabinoids enhance the antinociception of morphine. The addition of subactive concentrations of delta 9-(THC) and morphine in combination to brain synaptosomes did not result in an enhanced decrease in [Ca++]i; however, this drug combination enhanced decreases in [Ca++]i in spinal cord synaptosomes. The combination of CP55,940 and morphine produced enhanced decreases in [Ca++]i in both brain and spinal cord synaptosomes. In brain synaptosomes, the combination of delta 9-THC and morphine produced an additive decrease in cAMP accumulation, whereas no significant change was observed with this combination in the spinal cord. Thus, the difference in the modulation of [Ca++]i but not cAMP in the brain in vitro may be a predictor of the greater-than-additive antinociceptive effects observe in vivo. PMID- 7886082 TI - Methadone levels in plasma, urine, and amniotic fluid of methadone-treated pregnant rats. AB - Methadone was administered in the form of a slow release emulsion to nonpregnant rats and pregnant animals at early, middle, or late gestation. Following a 48-h treatment period, plasma, urine, and amniotic fluid were analyzed for methadone and its two major metabolites using solid-phase extraction and reversed-phase HPLC. Methadone and its primary metabolite were detected in plasma and urine of all rats with levels of both compounds comparable at all stages of gestation. No significant difference was found for either methadone or its primary metabolite between gestation groups and nonpregnant animals. Amniotic fluid collected in middle and late gestation groups contained methadone and primary metabolite at levels similar to that of maternal plasma. These data show that methadone can be detected in plasma, urine, and amniotic fluid following short-term treatment of pregnant rats with the opiate. Methadone levels did not alter during pregnancy and were, in fact, similar to that of nonpregnant animals. These results indicate that the fetal environment contains methadone levels comparable to that of the maternal circulation. PMID- 7886083 TI - Effects of brain tissue hydrolysate on synaptic transmission in the hippocampus. AB - A mix of peptides and amino acids obtained from porcine brain tissue (Cerebrolysin) has been shown to affect passive avoidance behavior in neonatal rats. To identify the active components and mechanisms of action, Cerebrolysin effects were studied in in vitro hippocampal slices. Cerebrolysin induced dose dependent suppression followed by a small rebound increase of synaptic responses in the CA1 but not dentate gyrus neurons. These actions may be due to peptides present in Cerebrolysin and may contribute to its reported behavioural effects. PMID- 7886084 TI - Opiate withdrawal intensity correlates with the presence of DSLET high-affinity binding. AB - The goal of this study was to compare the characteristics of mu- and delta-opioid receptors in the cortex of DBA/2 and C57BL/6 mice, which differ in sensitivity to the long- and short-term effects of morphine. The characteristics of mu-opiate receptors were not different in the cortex of both strains. Both high- and low affinity binding sites of DSLET, a specific ligand of delta-opiate receptors, were present in the cortex of C57BL/6 mice, whereas the high-affinity binding sites were not found in the cortex of DBA/2 mice. The absence of high-affinity DSLET binding sites, which are similar to the delta 2 type of opioid receptors, may explain the less intensive naloxone-precipitated withdrawal reaction of DBA/2 as compared with C57BL/6 mice. PMID- 7886085 TI - Dissipation of contingent tolerance to the anticonvulsant effect of diazepam: effect of the criterion response. AB - The effect of convulsive stimulations on the dissipation of tolerance to the anticonvulsant effect of diazepam was investigated using the kindled-convulsion model. Amygdala-kindled rats were rendered tolerant to diazepam's anticonvulsant effect by 25 "bidaily" (one/48 h) diazepam injections (2.5 mg/kg), each followed 1 h later by a convulsive stimulation. They were then divided into nine groups for the tolerance-dissipation phase of the experiment. Of the nine groups, three received bidaily control handling for one trial, three trials, or seven trials; three received bidaily saline injections, each 1 h before a convulsive stimulation, for one, three, or seven trials; and three received bidaily diazepam injections, each 1 h after a convulsive stimulation, for one, three, or seven trials. Finally, each rat received a tolerance-retention test (i.e., a diazepam injection followed 1 h later by a convulsive stimulation) 48 h after its last tolerance-dissipation trial. The tolerance dissipated gradually but completely over the 4-, 8-, and 16-day test intervals in the rats that received a convulsive stimulation before each injection during the tolerance-dissipation phase, whether they were injected with saline or diazepam; in contrast, tolerance did not dissipate in the rats that received saline injections but no stimulations. Remarkably, the discontinuance of the bidaily diazepam injections, even for 16 days, was not sufficient to dissipate the tolerance that had developed to diazepam's anticonvulsant effect; nor was the continuation of the bidaily diazepam injections sufficient to keep tolerance from dissipating.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886086 TI - Effects of an ectodermal microceptor preparation on motor coordination in cerebellar mutant mice. AB - Lurcher mutant mice, characterized by degeneration of the olivocerebellar system, and dystonia musculorum (dt) mutant mice, characterized by degeneration of spinocerebellar fibers, were treated with an ectodermal microceptor preparation (EMP), a compound containing natural substances derived from embryonic bovine ectodermal tissue, or with placebo, and evaluated in motor coordination tests. EMP-treated lurchers, but not dt mutants, were quicker to initiate movement than placebo-treated controls in the inclined beam test. No group differences were found in terms of distance travelled on the beam or in motor coordination assessed in a more challenging coat-hanger test. These results indicate that ectodermal microceptors may improve movement initiation of cerebellar-related disorders in animals, but that these effects are test and disease-specific. PMID- 7886088 TI - Acute ethanol administration in diestrus-2 in the rat on pulsatile prolactin and LH release. AB - Exposure to ethanol is followed by changes in reproductive function in man and animals, characterized by modifications in the secretion patterns of prolactin and luteinizing hormone (LH). As both hormones are secreted in an episodic fashion, the present work was undertaken to study the effects of acute ethanol administration on pulsatile prolactin and LH secretion patterns in adult female rats. Rats were previously cannulated to allow a continuous blood withdrawal to study the pulsatile patterns of prolactin and LH. The mean values of prolactin during the bleeding period and the absolute pulse amplitude of prolactin peaks were significantly increased by acute ethanol administration, whereas a significant decrease of relative pulse amplitude and frequency of this hormone was observed. On the other hand, ethanol administration increased the mean serum LH levels and the absolute and relative amplitudes of LH peaks. Ethanol treatment did not modify either frequency or duration of LH peaks. These data suggest that acute ethanol administration in adult female rats is followed by changes in the pulsatile prolactin and LH secretory patterns, which might be part of the mechanism to explain ethanol effects on the endocrine system. PMID- 7886087 TI - Efficacy of HI-6 and HLo-7 in preventing incapacitation following nerve agent poisoning. AB - The therapeutic efficacy of the oximes HI-6 and HLo-7 (132.5 mumol/kg), in combination with atropine, in soman- or tabun-intoxicated guinea pigs was compared, particularly with respect to recovery of shuttlebox performance and electroencephalograms (EEGs). After 1.5 x LD50 soman SC, therapy with HI-6 or HLo 7 resulted in survival of 87.5% of the animals in each group. In both groups postintoxication performance decrements and EEG abnormalities lasted approximately 2 weeks after intoxication. After 3 x LD50 soman all HLo-7-treated animals died within 5 h; 70% of the HI-6-treated animals were still alive after 8 h; however, only 10% survived more than 24 h. After 2 x LD50 tabun 36% of the HI 6-treated animals died; HLo-7 prevented lethality and led to faster recovery of performance and EEG than after HI-6. Even after 7.5 x LD50 tabun, followed by HLo 7, full recovery was reached within 1 week in the surviving animals (82%). In soman-intoxicated guinea pigs HI-6 is therapeutically slightly more effective than HLo-7. HLo-7 is far more effective, under similar conditions, against tabun intoxication than HI-6. PMID- 7886089 TI - Effects of the delta-opioid agonist, [D-Pen2,D-Pen5]-enkephalin, on fetal lamb EEG. AB - Opiates are known to exert biphasic effects on level of arousal, with excitation at low doses and depression at higher doses. It has been suggested that this dual excitatory and depressant actions of opiates may be mediated by different receptor subtypes. We have previously shown that activation of mu 1-opioid receptors evoked EEG activation in the fetal lamb. The purpose of the present study was to quantitate the effects of DPDPE, a highly selective delta-opioid agonist, on fetal EEG. When infused ICV (4.6-154 nmol/h), DPDPE elicited dose dependent activation of fetal EEG, with a reduction in power distribution in the delta (1-4 Hz) band, and an increase in the beta (15-32 Hz) band. This activation was reflected by an increase in the spectral edge frequency. This EEG activation was greatly attenuated at DPDPE doses greater than 154 nmol/h, resulting in a U shaped dose-response curve. The EEG activation was completely blocked by naloxone or naltrindole (delta antagonist), but not by naloxonazine (mu 1 antagonist). These results indicate that the activation of delta-opioid receptors will evoke EEG activation in the fetal lamb. PMID- 7886090 TI - Anxiolytic-like effect of the GABA-transaminase inhibitor vigabatrin (gamma-vinyl GABA) on rat exploratory activity. AB - Vigabatrin (gamma-vinyl GABA, GVG) is an irreversible inhibitor of GABA transaminase (GABA-T). This study addressed the question of whether or not the inhibition of GABA-T has an anxiolytic effect in rats. Diazepam (1.5 mg/kg) and GVG (50 and 500 mg/kg) increased the tendency of rats to explore in the elevated plus-maze test, whereas the effect of general locomotor activity was diminished. The sedative effect of GVG (500 mg/kg) was more pronounced 6 h than 2 h after IP administration. The present findings suggest that even a partial inhibition of GABA-T results in a reduction of anxiety measures in a novel environment. PMID- 7886091 TI - Nicotine reverses scopolamine-induced impairment of performance in passive avoidance task in rats through its action on the dopaminergic neuronal system. AB - Interest has recently focused on tobacco and/or nicotine in relation to senile dementia of the Alzheimer type because the population of patients with this disease among tobacco smokers is significantly smaller than in nonsmokers. We investigated whether, in relation to the dopaminergic neuronal system, nicotine was effective in ameliorating the impairment of performance in passive avoidance tasks in rats induced by scopolamine, an inhibitor of muscarinic acetylcholine receptors. Scopolamine and nicotine were coadministered to rats 30 min before the acquisition trial. Some rats received scopolamine alone; they showed much shorter step-through latency (STL) than the control group in the retention test. Nicotine significantly prolonged the decreased STL induced by scopolamine. The effects of nicotine were inhibited by the preadministration of mecamylamine, SCH 23390, and (-)sulpiride, which are nicotinic acetylcholine, D1, and D2 receptor antagonists, respectively. These results suggest that nicotine, by activating the nicotinic acetylcholinergic and dopaminergic neuronal systems, ameliorates the impairment of performance in the passive avoidance task induced by a muscarinic acetylcholine receptor blocker. PMID- 7886092 TI - Haloperidol-induced decrements in force and duration of rats' tongue movements during licking are attenuated by concomitant anticholinergic treatment. AB - To investigate the hypothesis that haloperidol's impairment of tongue protrusion in rats is Parkinson-like, the effects of centrally active scopolamine hydrochloride (0.1 or 0.2 mg/kg, SC) were evaluated in 36 rats that were also administered haloperidol (0.06, 0.12, or 0.24 mg/kg, IP). Rats were trained to lick water from a force-sensing disk, and the peak force and duration of each tongue contact were recorded along with the number of licks emitted in a 2-min session. Scopolamine hydrochloride significantly reversed haloperidol-induced deficits observed for peak force, duration, and number of licks. When given alone, scopolamine hydrochloride decreased peak force and duration. Fourier methods showed that the basic rhythm of licking was slowed by scopolamine hydrochloride but not by haloperidol. Taken together, the data suggest that central nervous system dopaminergic-cholinergic interactions importantly modulate tongue dynamics in the rat in a manner consistent with such interactions in neuroleptic-treated human patients. PMID- 7886093 TI - Influence of the estrous cycle and estradiol on the behavioral effects of amphetamine and apomorphine in rats. AB - This experiment was designed to investigate the influence of hormonal status of the rat on the effects of two doses of an indirect-acting dopamine agonist (amphetamine 0.25 and 1.0 mg/kg, IP) and a direct-acting dopamine agonist (apomorphine 62.5 and 250 micrograms/kg, SC) on the acquisition of conditioning avoidance responses (CARs) and the performance of some spontaneous behaviors. Active conditioned avoidance was improved by amphetamine in all the groups except in females at diestrus; apomorphine improved this response only in females at estrus and in ovariectomized rats after estradiol replacement, but the avoidance response was deteriorated in males and females at diestrus and after ovariectomy without estradiol replacement. Both dopaminergic drugs had contrasting effects on motor activity, number of rearings, and number of head shakes according to the hormonal status of the rat. Only the time spent in grooming behavior decreased after the treatment with both dopamine agonists in all of the five groups studied. These results provided behavioral evidence for the hypothesis that dopaminergic activity in the CNS is affected distinctively by modifications in the sexual hormone status (gender, estrous cycle, ovariectomy, and estradiol replacement). Relationships between ovarian hormones and dopaminergic system are discussed. PMID- 7886094 TI - Comparison of motor reflex and vocalization thresholds following systemically administered morphine, fentanyl, and diazepam in the rat: assessment of sensory and performance variables. AB - The relative influence of systemically administered morphine, fentanyl, and diazepam on the thresholds of spinal motor reflexes (SMRs), vocalizations elicited during stimulation (VDSs), and vocalization afterdischarges (VADs) was assessed. Responses were elicited by applying graded electric current to the tail. Performance (latency and amplitude) of all three responses was monitored to determine whether elevations in threshold were confounded by performance decrements. All three drugs were found to elevate VAD thresholds more readily than VDS and SMR thresholds. VADs were also most susceptible to the deleterious effects of these drugs on motor performance. Nevertheless, across the dose range of morphine and fentanyl that elevated thresholds of all three responses without disrupting the performance of any response, the order of susceptibility to threshold increases remained VAD, VDS, and SMR. Diazepam also elevated VAD thresholds more readily than VDS thresholds across a dose range that failed to disrupt performance of either response. SMR thresholds were only elevated by diazepam when administered in doses that significantly disrupted performance. Results are discussed in terms of supporting the validity of VADs as a model of the affective-motivational dimension of pain. PMID- 7886095 TI - High-frequency ultrasonic vocalization induced by intracerebral glutamate in rats. AB - Direct injection of glutamate, a neuroexcitatory agent, into the anterior hypothalamic-preoptic area of the rat brain induced ultrasonic vocalization. This vocalization was characterized by short-duration calls (below 60 ms) of high sound frequency (pitch), mostly above 40 kHz, and was similar to the known 50-kHz vocalization observed in natural situations. The glutamate-induced vocalization was dose dependent within the dose range of 16.9-67.6 micrograms and was antagonized by local pretreatment with MK-801, an NMDA antagonist. The increasing dosage of glutamate induced more calls and had a significant influence on frequency and intensity of emitted ultrasound. The average sound frequency increased whereas the mean sound intensity decreased with the dosage of glutamate. On the other hand, the mean duration of a single call and the bandwidth did not significantly change with doses of glutamate. Injection of carbachol, a muscarinic cholinomimetic agent, into the same brain sites as glutamate, induced a different type of ultrasonic vocalization with low sound frequency and long call duration, known as 22-kHz calls. The results suggest that high sound frequency, short-duration calls (50 kHz) and low sound frequency, long duration calls (22 kHz) have different neurophysiological and neurochemical mechanisms. PMID- 7886097 TI - The 5-HT2 receptor antagonist ketanserine prevents electroconvulsive shock- and clonidine-induced amnesia. AB - The 5-HT2-selective antagonist ketanserine was examined for its ability to prevent electroconvulsive shock (ECS)- or clonidine-induced performance deficit in the passive avoidance situation (step-down) in rats. The posttrain intraperitoneal injection of ketanserine at doses of 3 and 10 mg/kg prevented the ECS- or clonidine-provoked amnesia upon retention tests given 3 h, 24 h, and 7 days after training. The present data favor the view that the selective modification of 5-HT2 receptors after training can prevent the performance deficit in step-down-trained rats and suggest a role of the 5-HTergic neurotransmitter system in memory. The results of this study further suggest that 5-HTergic receptor antagonists might be useful in treatment of cognitive disorders. PMID- 7886096 TI - Butorphanol increases food-reinforced operant responding in satiated rats. AB - In the present series of studies we examined the effect of butorphanol tartrate on food-reinforced operant responding in satiated rats. In the first experiment, 8.0 mg/kg butorphanol was administered subcutaneously, once per day for 4 days, to satiated rats responding under an fixed ratio 10 (FR 10) reinforcement schedule. In the second experiment, butorphanol (0, 0.3, 1.0, 3.0, 10.0 mg/kg) was administered to satiated rats responding under an FR 80 (first pellet) FR 3 (subsequent pellets) reinforcement schedule for 4 consecutive days. Repeated butorphanol administration increased total amount of food consumed over sessions in both experiments. Under the FR 80 schedule component, butorphanol initially increased latency to acquire the first pellet, an effect attenuated by repeated administration. Whereas vehicle administration was associated with consumption of relatively large quantities of food within the first 10 min of receiving the first pellet, butorphanol was associated with continued feeding as the session progressed. These data suggest that butorphanol-induced food intake is associated with maintenance rather than initiation of feeding. PMID- 7886098 TI - The effect of metoprine on glucoprivic feeding induced by 2-deoxy-D-glucose. AB - Metoprine is a histamine N-methyltransferase inhibitor that elevates endogenous histamine (HA) levels. Because the histaminergic mechanism may be involved in the regulation of feeding behavior as well as in body glucose homeostasis, the effect of metoprine on glucoprivic feeding was studied in Wistar rats. Although metoprine treatment (10 and 20 mg/kg, IP) decreased feeding, the rats still responded to the administration of 400 mg/kg of 2-deoxy-D-glucose (2-DG) by increasing their feed intake. No difference was seen in the 6-h cumulative feed intake after administration of 2-DG between the metoprine- and solvent-treated rats. However, the response was delayed, and with 20 mg/kg metoprine the feed intake was significantly reduced during 2 h after 2-DG application. Both 2-DG and metoprine elevated plasma glucose concentration despite their opposite effects on feeding. Hypothalamic HA or its metabolite levels were not affected by 2-DG. The results suggest that the effects of metoprine and 2-DG are largely independent of each other, and that the feeding modulating function of HA is on such a level that it does not prevent the glucoprivic emergency response. PMID- 7886099 TI - PRE-084, a sigma selective PCP derivative, attenuates MK-801-induced impairment of learning in mice. AB - We investigated the effect of the sigma selective PCP derivative PRE-084 on the impairment of learning induced in mice by the noncompetitive NMDA antagonist MK 801. Learning capacities were evaluated using the spontaneous alternation in a Y maze test for spatial working memory, the step-down passive avoidance and the elevated plus-maze test for long-term memory. At doses about 1 mg/kg IP, PRE-084 significantly attenuated MK-801 (0.2 mg/kg IP) induced impairment of learning. The dose-response curve was bell-shaped which is typical for cognition enhancers. The effect of PRE-084 was antagonized by BMY-14802 (10 mg/kg IP) and suppressed by a chronic treatment with haloperidol (4 mg/kg/day SC for 7 days). Furthermore, PRE-084 did not affect scopolamine (1 mg/kg SC) induced amnesia but significantly attenuated mecamylamine (10 mg/kg IP) induced amnesia. These results show that sigma sites mediate a modulation of the NMDA receptor complex-dependent learning processes and may similarly affect the cholinergic nicotinic memory processes. Moreover, the PCP derivative PRE-084, acting selectively at sigma sites, reverses the amnesia induced by a drug acting at the PCP site. PMID- 7886100 TI - Induction of maternal behavior by mouse neonates: influence of dam parity and prenatal oxazepam exposure. AB - The aim of the present report was to investigate the influence of pup stimulus properties and female parity on mouse maternal behavior. Outbred CD-1 mouse pups, prenatally exposed to either the vehicle (VEH) or oxazepam (OX, 15 mg/kg twice/day on pregnancy days 12-16) and fostered to untreated dams at birth, were offered as a stimulus on postnatal days 4, 6, and 8 to four groups of females that differed in maternal experience: virgin, experienced virgin females, primiparae, and biparae. Maternal behavior was observed during a 15-min session each day. Virgin females were less involved in crouching behavior than primiparae. Pups, age, and prenatal oxazepam showed interactive effects on maternal care, particularly by increasing licking and nest-building activities and decreasing still-out behavior. Moreover, dams receiving younger pups showed high levels of both locomotor activity and rearing. The present findings point to the need for a better understanding of mother-pup interactions in studies aimed at characterizing drug and toxicant effects on both animal and human development. PMID- 7886101 TI - Effect of nicotine, lobeline, and mecamylamine on sensory gating in the rat. AB - In normal subjects, if an acoustic startle stimulus is immediately preceded by a small brief change in background noise intensity, the magnitude of the subsequent startle response is decreased. This prepulse inhibition (PPI) of an acoustic startle response has been shown to be associated with sensorimotor gating. PPI is disrupted in schizophrenic patients and has been linked to attentional disorders characteristic of this disease. We tested the effects of (-)-nicotine, (0.19, 0.62, and 1.9 mumol/kg IP) (equivalent to 0.03, 0.1, and 0.3 mg/kg base) and the nicotinic cholinergic receptor (nAChR) channel blocker, mecamylamine (5.0 and 50 mumol/kg IP) (equivalent to 1.0 and 10.0 mg/kg) on PPI of the acoustic startle response in the rat. Nicotine increased the PPI at the lowest prepulse signal levels but not at the stronger levels. Mecamylamine was without effect at 5.0 mumol/kg, but the 50 mumol/kg dose decreased the inhibition at both weak and strong prepulse (PP) levels. Mecamylamine (5.0 mumol/kg) pretreatment did not block the (-)-nicotine-induced increase in PPI. Lobeline (0.19, 0.62, 1.9, and 6.2 mumol/kg IP) (equivalent to 0.071, 0.23, 0.71, and 2.3 mg/kg) was without effect. These results are consistent with a mecamylamine-insensitive effect of nicotine to improve gating in normal rats. The nAChR subtype involved in producing nicotine's increase of PPI needs further investigation. PMID- 7886102 TI - Continuous or intermittent cocaine administration: effects of flupenthixol treatment during withdrawal. AB - Research indicates that chronic daily cocaine injections produce sensitization to, while the chronic continuous infusion of cocaine produces tolerance to, its behavioral and neurochemical effects. The present experiments examined whether flupenthixol administration during withdrawal would attenuate/eliminate the behavioral effects produced by these administration regimens. The rats were pretreated for 14 days with either continuous or intermittent daily injections of cocaine, and were then withdrawn from the pretreatment regimen for 7 days. On days 1-5 of the withdrawal period, subjects received a daily 0.125-2.0 mg/kg IP injection of flupenthixol. Then on day 7 of withdrawal from the cocaine pretreatment, all rats were given a 15.0 mg/kg IP injection of cocaine. Their behavior was rated according to a modified version of the Ellinwood and Balster (6) scale for 60 min. The results indicated that flupenthixol treatment during withdrawal eliminated the tolerance normally associated with the continuous infusion of cocaine. However, this effect of flupenthixol was not dose dependent: the lowest dose had the same effect as the highest dose of flupenthixol. In the cocaine-injection subjects, flupenthixol had a slight but statistically significant reduction in the behavioral effects of cocaine. The same was true in the saline-control rats, except for the highest dose of flupenthixol, which had a significant enhancing effect on the behavioral response to cocaine. The present results suggest that the current procedures may represent an effective screening methodology for potential cocaine pharmacotherapies. PMID- 7886103 TI - Effect of changes in swimming area on results of "behavioral despair test". AB - Our previous observations have revealed that the total time spent in immobility and time to reach complete immobility (latency) vary with the diameter of the cylindric chamber where mice are forced to swim in the behavioral despair test. Therefore, we investigated the effect of changing the test conditions of the original Porsolt test. Mice were forced to swim for 15 min in chambers with 10 cm (original diameter of the Porsolt's forced swimming chamber), 20, 30, and 50 cm diameter in 20 cm deep water. Total time spent in spells of immobility during the observation period from third to sixth (inclusive) minutes and time to reach complete immobility were measured. In addition, a possible correlation between the rotatory locomotor activity of mice during swimming as assessed by the number of tours per minute and effect of antidepressant drugs on it was investigated. Total duration of spells of immobility was shorter and the latency was longer in tests carried out in chambers with 10 cm diameter. Increasing the diameter of the cylinders made it possible to distinguish the antidepressant drugs from caffeine, anticholinergics, and antihistaminics, which gave a false positive response in 10 cm diameter cylinders, but not in cylinders with larger diameters. Increasing the diameter of the chambers to 20 and 30 cm also allowed to study the selective effect of the antidepressants, namely, the rotatory locomotor activity during swimming. The extension of the test period to 15 min increased the reliability of the measurement of the time to reach complete immobility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886104 TI - Vasopressin inhibits food intake in pygmy goats by activation of alpha 1 adrenergic receptors. AB - The hypophagic effect of intraperitoneally injected VP (1.5 micrograms/kg) was blocked by concomitant injection of the alpha 1-adrenergic antagonist prazosin (27 and 40 micrograms/kg). Both the alpha 2-adrenergic antagonists idazoxan (300 micrograms/kg) and yohimbine (500 micrograms/kg) and the beta-adrenergic antagonist propranolol (500 micrograms/kg) failed to block the hypophagia induced by VP (1.5 micrograms/kg). The results suggest that the hypophagic effect of VP is mediated by alpha 1-adrenergic receptors. PMID- 7886105 TI - Bromocriptine, a D2 receptor agonist, lowers the threshold for rewarding brain stimulation. AB - Drug-induced lowering of brain stimulation reward threshold can serve as a model for the pharmacological activation of reward pathways. Here, the effects of bromocriptine, a direct D2 dopamine receptor agonist, on reward thresholds were investigated. Bromocriptine administration resulted in the significant lowering of threshold levels in all test animals, suggesting that this agent can activate the same reward processes as do abused substances such as cocaine and morphine. PMID- 7886106 TI - Differential changes in rat brain noradrenaline turnover produced by continuous and intermittent restraint stress. AB - This experiment was performed to investigate differential effects of continuous and intermittent restraint stress on noradrenaline (NA) turnover in brain regions of male Wistar rats by measuring levels of a major metabolite of NA, 3-methoxy-4 hydroxyphenylethyleneglycol sulfate (MHPG-SO4) levels, as well as by measuring levels of plasma corticosterone and organ weights of the thymus, spleen, and adrenal glands. Rats in the 15-min and 30-min intermittently stressed groups showed significantly larger increases in MHPG-SO4 levels in most brain regions relative to those in the 90-min and 180-min continuously stressed groups, even though the total stress duration was equal or shorter. Body weight loss and loss of relative thymus weight in the 15-min intermittently stressed groups were the most marked among the five treatment groups. These findings suggest that stress rest cyclicity is critical in determining the extent of stress-induced brain NA turnover and peripheral physiological responses. PMID- 7886107 TI - Regional changes in dopamine and serotonin activation with various intensity of physical and psychological stress in the rat brain. AB - The present study examined whether regional patterns of brain dopamine (DA) and serotonin (5-HT) activation after physical and psychological stress depend on the intensity of that stress. Monoamine concentrations (DA, 5-HT, and their metabolites) were measured using high-performance liquid chromatography with electrochemical detection in eight brain regions of rats exposed to two different intensities of foot shock stress for 30 min (1.5 mA or 2.5 mA) or conditioned fear stress (CFS, after single or repeated foot shock). A low level of foot shock selectively increased the DA metabolism in the medial prefrontal cortex (mPFC), whereas a high level of foot shock increased it in most of the brain regions examined in the present study. A low level of foot shock did not increase the 5 HT metabolism in any regions, but a high-intensity shock increased the 5-HT metabolism in the mPFC, nucleus accumbens, and lateral hypothalamus. Rats that received high-intensity shock displayed more freezing than those that received low-intensity shock in a conditioned fear paradigm (24 h after receiving foot shock, the animals were placed in a shock chamber without being given shock), indicating an augmentation of conditioned fear. The increased DA and 5-HT metabolism were especially marked in the mPFC after CFS following a single foot shock session (2.5 mA). Rats that were repeatedly exposed to 2.5 mA foot shock for a period of 10 days displayed a greater degree of freezing induced by CFS than those given only one foot shock session, indicating an augmentation of fear and stress intensity. CFS after repeated foot shock, like foot shock per se, increased the DA metabolism in most of the brain regions except for the striatum and increased the 5-HT metabolism in the mPFC, nucleus accumbens, and amygdala. These results suggest that regional patterns of brain DA and 5-HT activation after physical and psychological stress depend on the intensity of that stress, although there are some differences between these stress; and that the more widespread activation of DA and 5-HT after more severe stress might relate to behavioral changes that reflect the augmentation of fear. PMID- 7886108 TI - Benzodiazepines promote the intermediate stage at the expense of paradoxical sleep in the rat. AB - The effects of diazepam, a long half-life benzodiazepine, midazolam and triazolam, two with short half-life, on the transitional stage between deep slow wave sleep and paradoxical sleep were studied in Wistar and WAG/Rij rats. This intermediate stage is characterized by the unusual association of cortical spindles and low frequency hippocampal theta rhythm. The main result was extension of the intermediate stage at the expense of paradoxical sleep by diazepam and triazolam by influencing only the duration of the intermediate stage and both the onset and maintenance of paradoxical sleep. Midazolam increased both intermediate stage and paradoxical sleep. Several differences in the qualitative modulation of the stage characteristics and between rat strains were found. In regard to the possible peculiar physiological significance of the intermediate stage, we conclude that benzodiazepines promote a transient pharmacological cerveau isole-like stage during sleep in rats. PMID- 7886110 TI - Cocaine preexposure sensitizes conditioned fear in a potentiated acoustic startle paradigm. AB - The consequences of chronic cocaine administration on fear-potentiated startle were evaluated in two experiments. Cocaine treatment (40 mg/kg) for 7 days prior to fear acquisition (light + shock pairings) had an attenuating influence on the ability of the conditioned stimulus (CS) to increase acoustic startle. When cocaine was administered in the context of the CS, following fear conditioning, a marked enhancement of potentiated startle was observed. In contrast, an extinction of the fear response was seen in saline and procaine animals repeatedly exposed to the nonreinforced CS. The results from control subjects injected with cocaine either in the shock chambers (contextual cues) or in their home cage environment, suggest that the systemic effects of this stimulant served to intensify the fear-eliciting properties acquired by the CS during fear conditioning. These findings demonstrate a cocaine sensitization of conditioned fear, and were related to the emotional and psychological disturbances associated with long-term cocaine use. PMID- 7886109 TI - Blockade of cannabinoid-induced antinociception by naloxone benzoylhydrazone (NalBZH). AB - We have recently shown that the antinociceptive effects, but not other behavioral effects of the intrathecally administered, but not intracerebroventricularly administered, cannabinoids, are blocked by the kappa antagonist, nor binaltorphimine. We employed naloxone benzoylhydrazone, a kappa3 agonist, and kappa1, mu, and delta antagonist, to better characterize the interaction of cannabinoids with kappa receptors. Naloxone benzoylhydrazone blocked the antinociceptive effects of both intrathecally and intracerebroventricularly administered cannabinoids. Because the cannabinoids are not blocked by mu and delta antagonists, the effects of naloxone benzoylhydrazone are presumed to occur through interaction with kappa receptors. Because the data indicate that naloxone benzoylhydrazone does not block kappa3 receptors, the data indicate that the cannabinoids may interact with kappa1 receptors in the production of antinociception. However, differences in the profile of activity of naloxone benzoylhydrazone and the cannabinoids at kappa receptors exist. Thus, the exact nature of the interaction of the cannabinoids and the kappa receptors to be elucidated. PMID- 7886111 TI - Behavioral effects of enantiomers of dizocilpine under two "counting" procedures in rats. AB - Stereoisomers of the N-methyl-D-aspartate antagonist dizocilpine (MK-801) were studied to determine whether behavioral effects on complex operants depend on reinforcement loss accompanying behavioral disruption. Rats earned food pellets if the run of consecutive left-lever presses preceding a trial-terminating right lever press approximated a target of 12. A percentile schedule reinforced any run closer to the target than two-thirds of the runs on the most recent 24 trials. Once the sequence was learned, half the subjects were shifted to a procedure that yoked reinforcement for each length run to the probability that length generated pellets during asymptototic percentile performance. Although these two procedures generate similar control run and reinforcement distributions, disrupting behavior reduced reinforcement probability far more under the yoked than the percentile procedure. Despite this difference in drug-induced reinforcement loss, both enantiomers produced similar dose-related decreases in run length and response rate under both procedures, with the (-) isomer approximately one log unit less potent than the (+) isomer. The absence of differential effects under these procedures diminishes the likelihood that reinforcement loss contributes to dizocilpine's effects, indirectly bolstering claims that dizocilpine directly affects learning. PMID- 7886112 TI - Increased alcohol intake in low alcohol drinking rats after chronic infusion of the beta-carboline harman into the hippocampus. AB - Harman (1-methyl-beta-carboline) has been shown to induce volitional drinking of ethyl alcohol in the rat. The purpose of this study was to examine the long-term effect of sustained delivery of harman into the dorsal hippocampus on the subsequent preference for alcohol in the genetically bred low alcohol drinking (LAD) rat. The individual pattern of preference for alcohol was first determined following a standard 3-30% alcohol self-selection test for 10 days. Thereafter, a cerebral cannula for constant infusion was implanted stereotaxically into the dorsal hippocampus. The cannula was attached to an osmotic minipump implanted subcutaneously, which was filled with either an artificial cerebrospinal fluid (CSF) vehicle or harman. Harman was delivered at a rate of 1.0 or 3.0 micrograms/h (i.e., 5.5 or 16.5 nmol/h, respectively) for a period of 14 days. Four days after surgery, the rats underwent a second 3-30% alcohol preference test for 10 days. Both doses of harman induced a threefold increase in the voluntary consumption of alcohol, expressed as g/kg per day. This effect of the beta-carboline seems to be specific for ethanol because its intake by the LAD rats was increased significantly only when concentrations from 11% to 30% were presented. Harman also enhanced the daily intake of food in a dose-dependent manner, but did not affect body weights or the volumes of water and total fluid consumed. These results, thus, demonstrate that the long-term exposure of hippocampal neurons to harman induces a preference for high concentrations of alcohol even in a line of rats lacking such a genetic predisposition. PMID- 7886113 TI - Drug discrimination using a Pavlovian conditional discrimination paradigm in pigeons. AB - Three pigeons were studied using a discriminated autoshaping procedure in which the presence or absence of methadone served as a conditional stimulus signalling which of two key light CSs would be followed by grain access. Drug sessions alternated randomly with no-drug sessions. Methadone (2.0 mg/kg) was administered prior to drug sessions in which a black vertical line on a white background served as CS+ and a diffuse white keylight served as CS- (reversed for bird 681). Saline or no injection was administered prior to no-drug sessions and the CS+/CS- contingencies were reversed. Discriminated performances emerged in which over 80% of the responding occurred to the appropriate stimulus. Stimulus control by methadone was assessed by presenting a range of methadone doses during 10-trial extinction sessions. A graded dose-effect curve was produced with low doses of methadone controlling saline-appropriate responding and higher doses controlling drug-appropriate responding. A range of doses of morphine, cocaine, and pentobarbital were also tested. Morphine produced methadone-appropriate responding while cocaine and pentobarbital did not. PMID- 7886114 TI - Periodic maternal deprivation alters stress response in adult offspring: potentiates the negative feedback regulation of restraint stress-induced adrenocortical response and reduces the frequencies of open field-induced behaviors. AB - The effects of periodic maternal deprivation (PMD) treatment on the adrenocortical stress response and on open-field behavior in adult offspring were investigated. Sprague-Dawley rat pups were deprived of mothers daily for 4.5 h during the first 3 weeks of life. PMD treatment resulted in lower corticosterone levels during restraint stress later in life. The result of dexamethasone suppression test indicated that PMD treatment caused a potentiation of the negative feedback function of adrenocortical response. These effects of PMD were not accompanied by an increased density of the hippocampal glucocorticoid receptor which has been reported to be induced in neonatal handling treatment (brief 15-min maternal deprivation). Serotonin (5-HT)-2 and beta-adrenergic binding sites were also examined in cerebral cortex and no change of binding capacities were induced by PMD treatment. In the open-field test, PMD treatment decreased the number of ambulations and rearings but did not affect a frequency of defecation. From these results, it is suggested that PMD treatment leads rats to be insensitive to environmental stimuli in adulthood. PMID- 7886115 TI - Effects of bromocriptine and haloperidol on ethanol withdrawal syndrome in rats. AB - The effects of bromocriptine and haloperidol, either alone or in combination, on ethanol withdrawal syndrome (EWS) have been investigated in rats. Bromocriptine (5 mg/kg 1P) inhibited wet dog shakes behavior and catatonia but potentiated the intensity of abnormal gait. The latency of the audiogenic seizures was prolonged by bromocriptine treatment. Haloperidol (0.5 mg/kg SC) decreased the intensity of stereotyped behavior but potentiated catatonia and agitation. It did not antagonize the behaviors induced by bromocriptine when injected in combination except the increased latency of the audiogenic seizures. The total intensity score of the EWS was not significantly different from that in untreated control. The results suggest that brain dopaminergic system may be involved to a limited extent in mediating the EWS in rats. PMID- 7886116 TI - Effect of lithium carbonate on activity level and circadian period in different strains of rats. AB - Lithium, an important pharmacological agent for the treatment of manic-depressive illness in humans, is known to lengthen the circadian period in a number of different species. Recent experiments, on the other hand, suggest that pharmacological agents may affect the circadian system indirectly through an increase or decrease of activity. To explore the interaction between pharmacological and activity effects on the circadian system, lithium was administered chronically to three different strains of rats (ACI, BH, and LEW) while wheel-running activity was studied quantitatively. Two of these inbred strains (BH and LEW) show profound abnormalities in their circadian activity rhythms, namely, a reduced overall level of activity and bimodal or multimodal activity patterns. Wheel-running activity was monitored for 4 weeks under baseline conditions, followed by 3 weeks with lithium treatment (0.3% Li2CO3 administered with food) and 4 weeks with normal food. Treatment with lithium (average intake per day = 3.6 +/- 0.2 mg) consistently decreased both the overall level and the circadian amplitude of the activity rhythm. The free-running period tau was slightly lengthened during lithium treatment, while the most dramatic effect on period was observed after lithium withdrawal. Correlation analysis, however, revealed only a small negative correlation between activity level and period length, which proved significantly only for animals of the ACI strain. Our data support the traditional interpretation that lithium lengthens circadian period by a direct pharmacological effect on the circadian pacemaker rather than through indirect effects of activity feedback. PMID- 7886117 TI - Dopamine D1 and D2 receptor ligands modulate the behaviour of mice in the elevated plus-maze. AB - To further our understanding of the potential role of dopamine in mechanisms of anxiety, the effects of four dopamine receptor ligands were examined in an ethological version of the murine elevated plus-maze test. The D1 receptor partial agonist, SKF 38393 (2.5-20.0 mg/kg), had minimal behavioural activity in this test, whereas the selective D1 receptor antagonist, SCH 23390 (0.025-0.2 mg/kg), had dose-dependent but behaviourally nonspecific effects. Quinpirole (0.0625-0.5 mg/kg), a D2 receptor agonist, had no effects at low doses but severely disrupted locomotion and exploration at the highest doses tested. In marked contrast to the lack of effect or nonspecific effects seen with the other ligands tested, the D2 receptor antagonist, sulpiride (2.5-20.0 mg/kg), produced an unambiguous anxiolytic-like profile under present test conditions. Although none of the doses tested adversely affected general activity, clear antianxiety effects were observed on both traditional and novel (i.e., risk assessment) behavioural measures. Data are discussed in relation to the relative importance of D1 and D2 receptor mechanisms in plus-maze anxiety, and the need to further assess D2 involvement through the use of more selective compounds. PMID- 7886118 TI - Diurnal and age-related changes in cerebrospinal fluid tele-methylhistamine levels during infancy and childhood. AB - Histamine is a neurotransmitter participating in many physiological functions and behavior, including control of arousal and modulation of the circadian rhythms. Diurnal variation in cerebrospinal fluid (CSF) levels of tele-methylhistamine (t MH), the main histamine metabolite, has been detected in several animal studies. In humans, such changes have not been described. Little is known on the development of histaminergic neurons in human brain. In children, the levels of CSF t-MH are not known. Therefore, we have measured the concentrations of CSF t MH in 81 children, age ranging from 3 months to 14.6 years. t-MH levels were higher in infants, and near adult values were measured in adolescents, the relation between CSF t-MH and age being; CSF t-MH = -0.217 years + 7.31 (n = 81, r = 0.26, p = 0.021). The mean t-MH concentration was higher during the daytime (7.07 +/- 0.46 pmol/ml, mean +/- SEM) than in the night (5.35 +/- 0.60 pmol/ml, p = 0.0019, ANOVA). The results show a development change in the concentration of t MH during childhood and a difference in t-MH levels between the daytime and night indicating a more active metabolism of brain HA in the waking period. PMID- 7886119 TI - Synthesis and pharmacology of two new histamine receptor antagonists related to ranitidine. AB - Pyridyl and 1,6-dihydropyridyl ranitidine analogues 1 and 2 were obtained by applying an improved modification of ranitidine synthesis. Compound 1 shows a selective H2 antagonistic activity while compound 2 is a non-selective histamine antagonist. PMID- 7886120 TI - [Lactones. 28. EPC-synthesis, structure and pharmacology of "lactonized" and "lactamized" analogues of acetylcholine]. AB - The enantiopure gamma-aminomethyl-gamma-butyrolactones (S)- and (R)-4a-d represent constrained analogues of acetylcholine, which were synthesized from D- or L-glutamic acid following two different routes. In addition, the corresponding lactames (S)- and (R)-10 were prepared by enantioselective synthesis. Only moderate activity was found at acetylcholine sites at the guinea pig atrium. PMID- 7886121 TI - Spin labeled amino acid nitrosourea derivatives--synthesis and antitumour activity. AB - The synthesis of three spin labeled derivatives of N-[N'-(chloroethyl)-N' nitrosocarbamoyl] amino acids is reported. The new nitrosoureas are obtained by condensation of the corresponding N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl] amino acid with 2,2,6,6-tetramethyl-1-oxyl-4-aminopiperidine using dicyclohexylcarbodiimide. Their chemical structures are confirmed by elemental analysis, IR, MS, and EPR spectroscopy. All newly synthesized compounds showed high antitumour activity against the lymphoid leukemia L1210 in BDF1 mice. PMID- 7886123 TI - [The effect of cytostatic drugs on immunocompetent cells]. AB - The cytotoxic and immunosuppressive effects of cytostatic drugs on immunocompetent cells and other cells of the haematopoietic system are known. The application of these drugs leads to irreversible bindings on and inside the DNA or on enzymes. In vitro studies demonstrate that these reactions occur at concentrations of about 100 micrograms/ml-10 ng/ml and a cell number of 10(6) MNC/ml. However, the same drugs show immunostimulating activities at much lower concentrations. Under such conditions the drugs cannot penetrate into the cells. Probably a drug-membrane-receptor-complex is formed and via signaling pathway certain gene regions are activated to produce cytokines and other regulator molecules. An understanding of these mechanisms is essential to the development of novel therapy strategies. PMID- 7886122 TI - Synthesis and pharmacological study of 5,6,8,9-tetrahydro-4H, 7H-pyrrolo[1,2 a]cyclopenta[b]thieno[3,2-f][1,4]diazepines. AB - The paper reports the synthesis of a series of 5,6,8,9-tetrahydro-4H, 7H pyrrolo[1,2-a]cyclopenta[b]thieno-[3,2-f][1,4]diazepines and the results of the study on their CNS activity in mice. The pharmacological properties of a previously prepared series of 5,6,7,8,9,10-hexahydro-benzo-analogs is also described. PMID- 7886124 TI - [Special qualification of a photometric procedure for determination of salicylic acid in therapeutic drug monitoring]. AB - A procedure for the determination of salicylic acid from human serum is presented. It is based on an acidic extraction, a basic reextraction and the detection of salicylic acid as its iron-III-complex by photometry. The procedure is quantitative over a wide range of linearity, easy to carry out and is especially suitable for therapeutic drug monitoring in the treatment of juvenile rheumatoid arthritis. PMID- 7886125 TI - Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. 1. Allopurinol. AB - The potentiality of molecular interaction of allopurinol (1) with beta cyclodextrin (beta-CD) was investigated by spectrophotometric methods. Differential UV spectrophotometry revealed an increase in the optical density of 1 in presence of beta-CD. Application of the continuous variation method to spectrophotometric measurements was attempted and revealed the formation of an 1:1 complex between 1 and beta-CD. The apparent solubility of the drug in presence of beta-CD was investigated at different temperatures. The solubility potentiating effect increases with increasing beta-CD concentration at 25-45 degrees C. On the other hand, the solubility of 1 decreases in presence of beta CD at 60 degrees C. The amount of drug solubilized in the form of the complex was determined at different temperatures and the results revealed that the solubilizing effect of beta-CD is entirely due to complex-formation. The stability constant of the complex was determined at different temperatures. The enthalpy and entropy of interaction were also computed from the values of the stability constant of the complex at different temperatures. The large negative enthalpic value indicates a strong involvement of dipoles and van der Waals interaction during complexation. The dissolution profiles of the drug, physical mixture of the drug and beta-CD as well as the prepared complex show an enhancement of drug dissolution from the prepared complex or the physical mixture compared to the drug per se which reveals an improvement of the dissolution property of 1 by beta-CD complexation. PMID- 7886126 TI - [Comparison of the bioavailabilities of erythromycin estolate and erythromycin ethylsuccinate dry suspension preparations in steady state]. AB - Relative bioavailability of erythromycin was determined after multiple-dose administration of erythromycin estolate in comparison to erythromycin ethylsuccinate both given as oral suspensions to twelve healthy volunteers. The daily erythromycin dose of erythromycin ethylsuccinate was 50% higher than the respective dose of erythromycin estolate; the dosage interval tau was 12 h for erythromycin estolate and 8 h for erythromycin ethylsuccinate. This scheme was planned in accordance to advices of the respective manufactures. Results of the study confirm the differences in extent of bioavailability of both erythromycin derivatives known from single-dose investigations. Furthermore, the experimental data show that a twice daily administration of 1000 mg erythromycin as erythromycin estolat resulted in sufficiently high plasma concentration of the active compound. PMID- 7886127 TI - Chemical composition and biological activity of leaf exudates from some Lamiaceae plants. AB - Leaf exudates from 39 species, belonging to 26 genera of Lamiaceae, have been isolated and their antibacterial and antiviral activity investigated. Some of the active compounds (ursolic acid, siderol and nepetalactone) were isolated and identified, most of them for the first time in the investigated plants. Some chemotaxonomic conclusions were drawn. PMID- 7886128 TI - Hidden fractals in pharmacodynamics. AB - The present report is an attempt to give relevance to the fractal theory in pharmacodynamics. It is shown, that analysis and discussion of pharmacological in vitro data keeping in mind that a pharmacological process is just a resultant of many different, also fractal, components, would sometimes lead to a more detailed examination of raw patterns of experimental data. PMID- 7886129 TI - [Anti-arrhythmic actions of amidinohydrazone substituted benzophenones. 7. Synthesis of C14 labeled (Z)- and (E)-2-amino-5 chlorbenzophenonamidinohydrazone]. PMID- 7886130 TI - [The protein binding of talinolol]. PMID- 7886131 TI - [The activity of drugs with homeopathic potency in the "yeast test"]. PMID- 7886132 TI - Liposomes as a tool in experimental pharmacology and toxicology. PMID- 7886133 TI - Two strikes: the role of black women in medicine before 1920. PMID- 7886134 TI - Lessons to be learned: by changing from "provider" to "watchdog". PMID- 7886135 TI - Evolution and neurobiology of altruism. PMID- 7886136 TI - Caring for patient care: artless observations about practice, price, and profit. PMID- 7886137 TI - Lessons from Homestead: the technologic and economic imperative in our health care system. PMID- 7886138 TI - Genetics and ethics. PMID- 7886139 TI - Levitt. PMID- 7886140 TI - Accepting the challenge of the past: Polish medicine in the period of transition. PMID- 7886141 TI - A health plan proposal. PMID- 7886142 TI - The enemy is "us"! PMID- 7886143 TI - Pulmonary circulation discovery. PMID- 7886144 TI - The coming resurgence of the generalist in medicine: its technological and conceptual basis. PMID- 7886145 TI - Is specific language impairment a valid diagnostic category? Genetic and psycholinguistic evidence. AB - Specific language impairment (SLI) is diagnosed when a child fails to develop language normally for no apparent reason: hearing and intelligence are adequate and the social environment is unexceptional. Definitions of SLI typically specify that the child must have a substantial discrepancy between language ability and non-verbal IQ. However, data from a twin study question the validity of this requirement, and indicate that SLI is not genetically distinct from less specific disorders where language impairment occurs in the context of low average or borderline non-verbal ability. A second question concerns the heterogeneous language symptoms seen in SLI: do these correspond to distinct conditions, or to different phenotypic manifestations of a common underlying disorder, or are they merely random variations resulting from unreliable assessments? The last of these possibilities is ruled out by the finding that twins who are concordant for language disorder show good agreement in terms of the pattern of language impairment. However, systematic variation in the age and ability of children in different SLI subgroups suggest that these may correspond to variable manifestations of a core inherited language disorder, rather than distinct diagnostic entities. PMID- 7886146 TI - The treatment of acquired aphasia. AB - A number of large-scale trials have established that language therapy with acquired aphasic patients can result in significant improvement. However, such trials use a variety of different treatments with patients with qualitatively varying disorders. The group results give no information about the treatments that were effective for particular types of problem. More recent studies of treatment have examined the effects of more closely defined treatments for more closely defined disorders. Treatment based on the facilitation of word retrieval show quite long-lasting effects from limited amounts of treatment, when the treatment gives either semantic or phonological information about the word, but the improvements are mostly limited to the items involved in treatment. The establishment of strategies for word retrieval based on patients' retained abilities results in more generalized improvement. The need for studies that relate analysis of a patient's disorder more closely to the process of treatment is discussed. PMID- 7886147 TI - Parallels and divergences in the acquisition and dissolution of language. AB - Analyses of the relation between the acquisition and dissolution of language have typically focused on whether or not the forms of language dysfunction that result from brain damage correspond to specific stages of language acquisition: the Regression Hypothesis. These analyses have not met with great success: although there are a number of superficial similarities between aphasic disorders and different stages of the immature linguistic system, there are also important differences. I will suggest that a focus on the behavioral similarities between language acquisition and dissolution is unlikely to be productive. A more productive course would be to focus, instead, on the general principles that constrain the acquisition and dissolution of language. PMID- 7886148 TI - Language in the infant's mind. AB - We review recent work that shows that, during the early stages of language acquisition, molar properties such as prosody are important to the infant. We argue that the specification of these structures allows the infant to learn the language processing routines that adults employ. PMID- 7886149 TI - The development of phonological skills. AB - In this paper we consider the nature and consequences of the development of phonological skills in children. We begin with evidence for developmental refinements in phonological processes. These developments, in turn, affect a variety of other skills. We consider two particular examples: the relationship between the development of speech skills and verbal short-term memory and the development of children's phonological awareness. The development of phonological awareness is related to the acquisition of literacy, which, in turn, brings about further refinements in phonological skills. PMID- 7886150 TI - Impairments of speech production and speech perception in aphasia. AB - The basis of speech production and speech perception deficits in aphasia relates to implementation and access rather than to the underlying representation or knowledge base of the sound structure of language. Speech production deficits occur on the phonological level in which the incorrect phonological form of the word is selected but is implemented correctly, and the phonetic level in which the correct sound segments are selected but articulatory implementation is impaired. Phonological deficits emerge regardless of lesion site, whereas phonetic deficits have a specific localized neuroanatomical substrate. Phonetic deficits are not linguistic but affect particular articulatory movements. Speech perception impairments emerge in nearly all aphasic patients, suggesting that the neural basis for speech perception is broadly distributed in the language hemisphere. The impairment reflects the misperception of phonetic features rather than a deficit in the auditory processing of speech and emerges particularly as the sound properties of speech contact the lexicon. PMID- 7886151 TI - From universal to language-specific in early grammatical development. AB - Attempts to explain children's grammatical development often assume a close initial match between units of meaning and units of form; for example, agents are said to map to sentence-subjects and actions to verbs. The meanings themselves, according to this view, are not influenced by language, but reflect children's universal non-linguistic way of understanding the world. This paper argues that, contrary to this position, meaning as it is expressed in children's early sentences is, from the beginning, organized on the basis of experience with the grammar and lexicon of a particular language. As a case in point, children learning English and Korean are shown to express meanings having to do with direct motion according to language-specific principles of semantic and grammatical structuring from the earliest stages of word combination. PMID- 7886152 TI - Impairment of sentence comprehension. AB - We examine two different forms of comprehension impairment, 'semantic dementia' and 'asyntactic comprehension', focusing on the assignment of thematic roles; the determination of who did it to whom. We show, first, that the loss of word meaning does not impede thematic assignment in semantic dementia, demonstrating that syntactic information, along with some knowledge of the verb, is sufficient for the assignment of thematic roles. Studies of normal subjects indicate, however, that this process is normally subject to semantic influences; asked to judge the plausibility of sentences, subjects respond faster when thematic assignment is semantically constrained. The sentence plausibility judgments of 'asyntactic' comprehenders (aphasics with diminished syntactic control over thematic assignment) show increased effects of these semantic constraints. We discuss these results in relation to current issues in sentence processing. PMID- 7886153 TI - Language and its biological context. AB - All reasonably functioning newborn humans learn any native language effortlessly. No other species can learn human language even with effort. Such facts indicate that young humans are similar in ways which match them to properties shared by the set of natural languages. We would expect some similarities to be found in the baby's brain and others in the surrounding environment. PMID- 7886154 TI - Disorders of sentence production. AB - Many process contribute to the speech production system. Brain damage can lead to a wide variety of disorders of the spontaneous production of sentences. Different symptoms of a sentence construction disorder, such as agrammatic and paragrammatic speech errors, are briefly described. An explicit model of the grammatical processes is proposed, and it is shown how the symptoms can be explained in terms of selective impairments to components of the model. The construction of subject-verb agreement in speech is treated in detail. PMID- 7886155 TI - Precursors of linguistic knowledge. AB - It is agreed that infants require pre-existing conceptual meanings to learn language, although little is known about what those meanings are. By default they have been assumed to be the sensorimotor schemas described by Piaget. However, sensorimotor schemas are not concepts and are not the right sort of representation for learning language. Recent research shows that along with sensorimotor schemas infants are simultaneously developing a rich conceptual system. I have proposed that these concepts are represented by sets of image schemas, each of which represents a meaning. Image-schemas are created by a process of perceptual analysis that redescribes perceptual information into simplified spatial representations. These representations allow language to be learned by providing an analogue-digital interface between the continuous process of perception and the discrete propositional forms of language. PMID- 7886156 TI - Words, words, words.... AB - Traditional accounts of vocabulary acquisition assume that children succeed by aligning the utterance of words with their environmental contingencies, a word-to world pairing. Experimental results suggest that such a procedure accounts for the acquisition of nouns but is insufficient for the acquisition of verbs. It is demonstrated that infants under two years of age systematically recruit the structural properties of sentences in which novel verbs occur to find their meanings: a sentence-to-world pairing procedure. PMID- 7886157 TI - Morphological errors and the representation of morphology in the lexical-semantic system. AB - Neuropsychological studies support the hypothesis that morphology is represented autonomously, both at the level of word meaning and at the level of word form. In output processes, morphologically organized semantic information activates lexical representations of roots and affixes, which are composed before production. In input processes, the stimulus is parsed along the morphological dimension, to access root and affix lexical representations, which in turn activate morphologically organized semantic information. Inflectional and derivational morphology are represented independently in the lexicon. Inflected words are fully decomposed; derived words are decomposed into base form+inflection. In aphasia, morphological errors in transcoding tasks always co occur with semantic and/or phonemic errors. Morphological errors in transcoding tasks require combined damage to morphological representations in the semantic lexical system and to sublexical conversion procedures; they co-occur with semantic errors when also root representations are damaged. The co-occurrence of morphological and phonemic errors can be accounted for by several hypotheses, but its theoretical meaning is still uncertain. PMID- 7886158 TI - Disorders of semantic memory. AB - It is now established that selective disorders of semantic memory may arise after focal cerebral lesions. Debate and dissension remain on three principal issues: category specificity, the status of modality-dependent knowledge, and the stability and sufficiency of stored information. Theories of category specificity have focused on the frequently reported dissociation between living things and man-made objects. However, other dimensions need theoretical integration. Impairments can be both finer-grain and broader in range. A second variable of importance is stimulus modality. Reciprocal interactive dissociations between vision and language and between animals and objects will be described. These indicate that the derivation of semantic information is constrained by input modality: we appear to have evolved separable databases for the visual and the verbal world. Thirdly, an orthogonal distinction has been drawn between degradation disorders, where representations are insufficient for comprehension, and access deficits, in which representations have become unstable. These issues may have their parallel in the acquisition of knowledge by the developing child. PMID- 7886159 TI - Language and communication in autistic disorders. AB - Communication problems form one of the key diagnostic criteria for autism, but there is a wide variety of manifestations. The theory that autistic individuals are unable to represent mental states can shed light on both the nature and range of communication impairments. This theory predicts that the specific communication deficit lies in the use of language to affect other minds. Language is not special in this respect, and is important only in so far as it may be used to give evidence of a speaker's thoughts and intentions. Thus, in autism, language level would be expected to relate strongly to performance on standard tests of theory of mind. Normal language acquisition appears to build upon the ability to recognize and orient towards ostensive behaviour. For this reason, it may not be necessary to postulate additional language impairments in order to explain the almost universal prevalence of language delay in children with autism. Autism, then, provides a model for studying the important distinction between language and communication, and demonstrates the vital part which mind reading plays in normal human verbal and non-verbal interaction. PMID- 7886160 TI - A model for rebound bursting in mammalian neurons. AB - In this paper we begin by simplifying our previous model of a thalamic neuron (Rose & Hindmarsh Proc. R. Soc. Lond. B 237, 289-312 (1989b)) by removal of the A current. A Ca(2+)-activated K+ current, with Ca2+ entering through T channels, is then added to give a model for a class of mammalian neurons in which the membrane potential oscillates in the subthreshold region following a hyperpolarizing current step. The properties of the model are represented using an experimentally observable bifurcation diagram. In the subthreshold region only three variables are required to explain the essential dynamic properties of the cell. In this three-dimensional space the solutions tend to lie on a surface which resembles a paraboloid. We use a simplified model of this model to explain both the dynamics of the solutions on this surface and the form of the bifurcation diagram. PMID- 7886161 TI - Resonance in a model of a mammalian neuron. AB - In this paper we show that for a small range of voltages the model described in the previous paper (Hindmarsh & Rose Phil. Trans. R. Soc. Lond. B 346, 129-150 (1994a)) will generate damped oscillations in response to a negative current pulse. As a consequence the cell has the property that it can be driven into bursting by periodic sinusoidal inputs close to the resonant frequency. The main objective of this paper is to analyse this resonant behaviour using the model of the model introduced in the previous paper. We derive analytical expressions which closely approximate the nonlinear resonance observed in the physiological model driven by a periodic sinusoidal input. This leads to the conclusion that resonance could play a role in synaptic transmission at relay nuclei in the mammalian brain. PMID- 7886162 TI - A model of intrinsic and driven spindling in thalamocortical neurons. AB - We add a slow hyperpolarization-activated inward current IH = gHmH (v-vH) to our previous model of rebound bursting (Hindmarsh & Rose Phil. Trans. R. Soc. Lond. B 346, 129-150 (1994a)) to give a four-dimensional physiological model, and a corresponding four-dimensional model of the model. The physiological model generates periodic 'bursts of bursts' or 'spindles' resembling those recorded experimentally in thalamocortical (TC) neurons. The model of the model is simplified to a two-dimensional system having a limit cycle which corresponds to the slow spindle oscillation of the physiological model. Analysis of the stability of this two-dimensional model allows us to divide the parameter space of the slope (gamma mH) and shift (theta mH) parameters of mH infinity (v) into regions in which the model generates spindles or continuous bursting. This enables us to determine the parameter values required for spindling in the physiological model and to explain the experimentally observed effects of noradrenaline. Next we examine whether a cell at a stable equilibrium point can be driven into spindling by applying a sinusoidal input at the resonant frequency. This is done by averaging the equations for the driven model of the model. Analysis of the stability of these averaged equations shows how the regions of the (theta mH, gamma mH) parameter space change when the system is driven by a sinusoidal input. This enables us to choose parameter values for a physiological model of a driven spindle. We show that if the physiological model is modified to include a voltage-dependent time constant for mH, spindles, similar to those of TC cells, can be obtained with a small Ca(2+)-activated K+ current. Finally our knowledge of the form of the bifurcation diagram and the conditions for resonance leads to a new suggestion for the roles of GABAA and GABAB inhibitory postsynaptic potentials when TC cells are driven into spindling by neurons of the nucleus reticularis thalami. PMID- 7886163 TI - Is there a natural homicide rate? PMID- 7886164 TI - Lunar phases and psychiatric hospital admissions. AB - To assess the lunar hypothesis as predictive of mental health emergencies and antisocial behavior, the relation of the lunar hypothesis and the occurrence of psychiatric hospital admissions of developmentally disabled adults was examined. The full moon phase of the lunar cycle did not explain a higher rate of hospital admission and accounted for only .007% of the variance. A critique of the methodology in prior research led to the suggestion that more immediate stressors and environmental factors are more plausible contributing factors to hospital admission. PMID- 7886165 TI - Job satisfaction of and return to work by occupationally injured employees. AB - The job-satisfaction scores of 107 work-injured employees were correlated with return to work status at 20 weeks postinjury. There was a slight tendency for the more satisfied employees to be back at work. PMID- 7886166 TI - Maternal sex-stereotyping of newborns. AB - Gender as a social category playing a role in the process of how mothers perceive their newborns was investigated. 94 primiparous mothers completed a survey that included a physical and an emotional scale on their newborn infants. Neither scale as a whole discriminated between the male and female newborns; however, a one-way analysis of variance did identify four statistically discriminating items. The four items evidence maternal perceptions that sex-stereotype males as having broad, wide hands, looking tall and large, looking athletic, and being mostly serious--not smiling but not crying. Maternal sex-stereotyped perceptions for daughters would be the inverse of these. 30 items gave similar maternal ratings between the two gender sets. These confirmed prior work in 1974 showing sex-stereotyped physical characteristics outnumber the emotional characteristics. The similarity of current conclusions to the 1974 data suggests less than expected fundamental parental attitudinal change due to increased societal interest and attention to gender and sex-stereotyping. PMID- 7886167 TI - Depression and sense of humor. AB - This research note provides partial confirmation of a negative relationship between depression and sense of humor previously reported by Deaner and McConatha in 1993. Here, for 213 women and 134 men, r was -.18. PMID- 7886168 TI - Neuropsychological symptoms in a cross-sectional sample of abstinent alcoholics. AB - This study examined the neuropsychological symptom reports of a cross-sectional sample of 205 abstinent alcoholics. Analysis indicated that early-abstinent alcoholics reported mild cognitive distress with a gradual course of observed recovery which eventually reached the normal range. The recovery process was essentially the same for both men and women. A nonsignificant increase in symptom reporting was found for subjects who were beyond the acute stage of detoxification, which is thought to reflect improved awareness of neuropsychological functioning. Symptoms of frustration were rated highest by alcoholics at all stages of abstinence. PMID- 7886169 TI - Sexual abuse as a correlate of women's alcohol abuse. AB - Scores on the Beck Depression Inventory for 23 alcoholic women (22 white and one Hispanic) who had been molested as children and 20 alcoholic women (17 white and 3 black) who had no memory of being molested as a child were compared. Significant differences showed the abused group scored significantly higher on the depression scale than the nonabused group. No significant difference was found on age at which the 2 groups began drinking regularly. The implications of these results are discussed. PMID- 7886170 TI - Depression and acculturation in Mexican-American women. AB - The purpose of this study was to examine the relationship between depression and acculturation in Mexican-American women. For this purpose, two samples of 67 women from social service agencies in Kansas City and 57 college women from South Texas were examined. Pearson product-moment correlations of scores on depression and acculturation suggested a nonsignificant association (-.02) for the South Texas sample, but a low negative significant relationship (-.29) for the Kansas City group. PMID- 7886171 TI - Sexual behavior of nonurban students in grades 7 and 8: implications for public policy and sex education. AB - In a study of 1,844 suburban and rural students in Grades 7 and 8 in public schools in Washington, Oregon, California, and Idaho, sexual activity was much lower than that reported by the popular media and in some scholarly journals. The difference was in part related to using measures other than asking the adolescents whether they had ever had sexual intercourse. The estimates based on those who have had sex more than just once decreased to 16% the number of adolescents who would be classified as sexually active. If the definition of sexually active is further limited to only those who have had sex recently (within the past 4 weeks), only 9% are sexually active. Further restrictions to those who have had sex 5 or more or 10 or more times reduce the percentage of sexually active adolescents to 6% and 2%, respectively. Over-all, the percentage of "sexually active" adolescents depends on the empirical definition of "sexually active," and there are many indications why "ever had sex" is not an adequate measure. PMID- 7886172 TI - Differential predictive power of the positively versus the negatively worded items of the Life Orientation Test. AB - A self-report measure of dispositional optimism, the Life Orientation Test, was administered to a group of 202 Hong Kong undergraduates. Consistent with prior findings, factor analysis yielded a two-factor solution with all positively worded items loaded on the first factor and all the negatively worded items loaded on the second. Prediction of physical symptom reports from scores on the two subscales was then tested with 85 subjects randomly selected from the original sample. Only the complete test and the subscale defined by the positively phrased items predicted symptom levels concurrently as well as prospectively over 3 wk. The negative subscale suggested by previous research as tapping pessimism rather than dispositional optimism showed no significant correlation with symptom levels. Moreover, when scores of the positive rather than the negative subscale were controlled, the significant correlation between scores on the Life Orientation Test and symptom reports was eliminated. These findings suggested a multidimensional view of the test and that the positive subscale may be sufficient to measure optimism validly. Implications of these for the personality dimensions of positive versus negative affectivity are also discussed. PMID- 7886173 TI - Attitudes toward homosexual behavior: effects of veteran status. AB - The present study examined the attitudes toward homosexual behavior of veterans of United States military service and nonveterans. Using a nationwide survey as the database, 1,293 veterans did not differ from 2,330 nonveterans in approval of homosexual behavior, as over 74% of each group expressed disapproval. PMID- 7886174 TI - Inclusive education in Finland: present and future perspectives. AB - The movement to integrate special education students into normal school classes started to develop in Finland in the 1960s. At the same time, the number of students labeled "special" in the Finnish comprehensive school system exploded from 2% to 17% of all school children. Presently, 84% of all special education placements are part-time placements. Special schools and special classes comprise 15% of all special education placements, while full inclusion is only 1% of all special education placements. Some factors affecting the current integration of special students and the development of integration are discussed. PMID- 7886175 TI - Anger, curiosity, and optimism. AB - We examined with 500 Italian subjects the relationship between the subscales of the State-Trait Anger Expression Inventory and a measure of the sense of well being, the Life Orientation Test. As predicted, associations were not significant with scores on the scale of optimism; however, all coefficients were negative and the smallest ones were with the Anger Control scale. We also correlated scores on state and trait curiosity with those on 3 anger-expression scales; values indicated these dimensions were also unrelated to anger. The results indicate that, while anger has been proposed as an important component in the association of emotions with health, the specific type of anger expression may not be critical for one's sense of well-being. They also suggest that the construct of curiosity deserves further study as a potential measure of one's sense of well being. PMID- 7886176 TI - Construct validation study of the Fear of Powerlessness Scale. AB - To establish construct validity with 129 subjects for the Fear of Powerlessness Scale parallels were drawn among Levenson's Locus of Control Scales, the Fear of Powerlessness, and the Desire for Control Scale. Analysis yielded significant correlations between scores on the Fear of Powerlessness Scale, the Desire for Control Scale (negative), and 2 of Levenson's Locus of Control Scales, the Chance Scale and the Powerful Others Scale (positive). PMID- 7886177 TI - A methodological comparison of survey techniques in obtaining self-reports of condom-related behaviors. AB - To obtain more accurate accounts of sexual attitudes and practices, researchers must explore innovative ways to overcome the reluctance of individuals to disclose sensitive and perhaps incriminating information about themselves. The differences among selected modes of inquiry and survey techniques used to gather self-reports about sensitive contraceptive behaviors among young adults were examined in this study. Comparisons were made between the randomized response versus the direct-inquiry survey techniques and personal interview versus self administered modes of inquiry relative to the reporting of sensitive condom related sexual practices of 352 students at a large northeastern university. Findings indicated that the "controlled-choice" randomized-response technique was less effective in obtaining self-reports about condom-related practices than were direct-inquiry techniques. Recommendations for investigations are proposed. PMID- 7886178 TI - Imposter feelings in disturbed adolescents. AB - 21 disturbed adolescents in a supervised day-care program had higher imposter scale scores than regular high school students. Imposter scores were associated with scores on a measure of general irrational thinking. PMID- 7886179 TI - Are schizophrenic symptoms different in patients with higher education? AB - Ratings of 87 symptoms on a Canadian sample of 108 DSM-III schizophrenics (41 men, 67 women) were unrelated (point biserial coefficients) to their education. The only exceptions to this trend were weak correlations with ratings of apathy, insight, and of premorbid adjustment. Patients with higher education were less frequently labelled as apathetic (r = .28) or as lacking insight (r = .26) and their premorbid adjustment was better (r = .25). None of the symptoms traditionally considered as markers specific for schizophrenia was significantly related to education. PMID- 7886180 TI - Causal attribution and affective response as mediated by task performance and self-acceptance. AB - Predictions derived from cognitive consistency theories, self-esteem theories, and ego-serving-bias theory concerning how students would make attributional and affective responses to their academic performance were investigated. 202 university students completed a measure of self-acceptance of their college ability and made attributional and affective responses to an hypothetical examination performance. Analyses showed that students receiving positive feedback perceived greater internal causality and responded with greater positive affect than students receiving negative feedback. Self-acceptance did not moderate the attributions or affective reactions. The results supported the ego serving-bias theory and provided partial support for self-esteem theory. Findings did not support predictions from cognitive-consistency theory. PMID- 7886181 TI - Symptom correlates and factor structure of the Health Professions Stress Inventory. AB - Generalizability, psychological symptom correlates, and the factor structure of the Health Professions Stress Inventory were assessed with a sample of 92 geriatric nurses. The inventory was designed to measure the sources and frequency of stress among nurses, physicians, and pharmacists; little is known, however, of the extent to which scores correlate with psychological symptoms or of the underlying dimensions of stress measured. Analyses showed high correspondence between responses of the geriatric nurses and the normative nurses as measured by mean values and Cronbach alpha. Factor analysis of the intercorrelations among items yielded 4 factors contributing to work-related stress, i.e., Lack of Perceived Enrichment Potential, Patient Care, Interpersonal Conflict, and Family Responsibility Conflict. Scores on the inventory correlated significantly with those of all SCL-90--R scales. PMID- 7886182 TI - Survey response rate as a function of age: a study among clergy. AB - A detailed questionnaire was mailed to 3,510 Anglican clergy with active responsibility for churches. Analyses showed a lower response rate among older clergy. PMID- 7886183 TI - Presence seeking and sensation seeking as motives for international travel. AB - Although independent research has identified presence seeking and sensation seeking as important motives for a variety of activities, there is sufficient conceptual overlap to suggest the concepts describe in part the same motive or are related. The possible relationship was examined in motives of students for international travel. Nonsignificant correlations suggest that, at least for this activity, they are differentiable. PMID- 7886184 TI - Test anxiety and academic achievement among South African university students. AB - Although studies in Western and a few developing countries have indicated students with low scores on test anxiety tend to perform better on academic tasks than those who score higher on test anxiety, at this South African university no statistically significant mean difference on a test in educational psychology was noted for 121 students who scored high on the Anxiety Achievement Test and those 117 who scored low. PMID- 7886185 TI - Prediction of recreational therapy behavior of hospitalized adolescents from a behavior classification instrument. AB - The purpose of this study was to estimate the validity of an instrument of the Adolescent Behavioral Classification Project in predicting behavior patterns of emotionally disturbed adolescents in an inpatient setting. Subjects (n = 126) were adolescents admitted to a state residential treatment unit across a period of 35 months. Predictor variables were scores on 17 or 25 factors of the instrument from both adolescents' own responses and their mothers' responses on their behalf. Criterion variables were 10 recreational therapy factors, especially 4 temporally stable factors, and length-of-time in treatment. 3 phases of the project were (I) behavior during initial stages of the therapy, (II) behavioral change after 3 months of therapy, and (III) length-of-time in treatment. In Phase I, both mothers' and adolescents' responses produced significant correlations with criteria; however, in Phase II only the adolescent students' 25 ABCP factors predicted behavioral change. In Phase III, adolescents' responses but not their mothers' responses classified the adolescents by length of-time in treatment. PMID- 7886186 TI - Further validation of the Indecisiveness Scale. AB - Scores on the Indecisiveness Scale have been shown to be correlated with scores on measures of obsessive-compulsive tendencies and perfectionism for women. This study examined the validity of the Indecisiveness Scale with 41 men whose mean age was 21.1 yr. Indecisiveness scores were significantly correlated with scores on measures of obsessive-compulsive tendencies and perfectionism. Also, undeclared majors had a significantly higher mean on the Indecisiveness Scale than did declared majors. PMID- 7886187 TI - Group differences in alcohol-creativity interactions. AB - A repeated-measures, balanced-order design was used to test for the effects of alcohol on creativity as measured by verbal forms of the Torrance Creativity Test. Social drinkers (8 men and 8 women) performed under 2 conditions, alcohol (dose = 0.83 ml ethanol/kg body weight) and a placebo. Significant group differences in the alcohol-creativity interaction were noted in that the performance of higher-scoring (in the placebo condition) subjects was impaired by alcohol whereas that of lower-scoring subjects was enhanced. PMID- 7886188 TI - Daily and weekly smoking habits: a Box-Jenkins analysis. AB - The objective of this research was to ascertain if there are different temporal patterns of smoking. The method of data collection was to use voluntary subject smokers who recorded their daily cigarette consumption for 84 days. Subjects had smoked more than 5 cigarettes per day throughout the previous year; 29 subjects kept accurate autorecords. The daily smoking data of each subject were analyzed via the time-series procedure ARIMA(p,d,q)(P,D,Q)s of Box and Jenkins. 15 subjects (52%) showed simple autoregressive smoking models for which smoking on any given day was a function of the number of cigarettes smoked on the previous day or days, but 13 subjects (45%) showed autoregressive models of weekly seasonality, i.e., the number of cigarettes smoked on any given day is a function of the number smoked on the same day of the previous week, and only 1 subject's data (3%) had unpredictable smoking patterns. PMID- 7886189 TI - Personality correlates of scores on the Depression-Happiness Scale. AB - The present aim was to estimate the internal reliability and convergent validity of the Depression-Happiness Scale. Internal reliability was .90, and higher scores on the Depression-Happiness Scale were associated with more internal control (.28), higher self-esteem (.36), and lower trait anxiety (-.69) among 45 undergraduates at the University of Ulster. The results provide some evidence for the validation of the Depression-Happiness Scale as well as confirming previous research on the correlates of happiness. PMID- 7886190 TI - Vulnerability Scale: a preliminary report of psychometric properties. AB - This work describes assessment of the psychometric properties of a self-report instrument, the Glover Vulnerability Scale. This scale was administered to a total of 11 groups (N = 695). Six of the groups were Vietnam combat veterans diagnosed as having Posttraumatic Stress Disorder (n = 531). The estimate of internal consistency was .88; the test-retest correlation over 4 wk. was .81. Convergent and discriminant validations were satisfactory based on the pattern of the scale's correlations with relevant MMPI subscales and demographic data. Scale scores also discriminated levels of functioning within the population diagnosed with Posttraumatic Stress Disorder and discriminated veterans diagnosed with Posttraumatic Stress Disorder from patients with major depressive disorder and anxiety disorder. Principal component factor analysis gave a 4-factor solution: social comfort, vulnerability, paranoia, and family trust. Over-all, the findings strongly support the clinical application of the Vulnerability Scale. PMID- 7886191 TI - Women at risk for homelessness: comparison between housed and homeless women. AB - The present study explored differences between women who are currently housed but are at risk for homelessness versus homeless women in a middle-sized city in the southeast. The research focused on experiences in the women's history which might explain some differences between homeless women and women who are at risk for homelessness but are currently housed through public-assistance programs. 98 women from a community emergency shelter and public-assistance programs were either interviewed or completed questionnaires. The questionnaires assessed the women's history of mental illness, employment and housing problems, physical and sexual abuse, drug and alcohol problems, and skills for building and maintaining relationships. The women were young (18-35 years), about 80% were single mothers and about 50% had children living with them. t tests for independent samples indicated that compared to 48 at-risk housed women, the 50 homeless women reported a history of more symptoms of mental illness, more instability of employment and housing, more physical and sexual abuse, more drug and alcohol problems, and fewer skills for interacting with others. When all variables were entered simultaneously into a multiple regression equation, only skills for interacting accounted for a significant proportion of the variability between the two groups of women. PMID- 7886192 TI - Dietary restraint as a predictor of reported weight loss and affect. AB - This study investigated dietary restraint as a predictor of subsequent reported weight loss. Neither chronic dieters nor nondieters reported actually losing weight over a 7-mo. period. With respect to recent weight change, restrained eaters reported both more recent weight loss and more recent weight gain than unrestrained eaters. Further, such weight changes had a much larger influence on their affect. It was concluded that chronic dieting is likely to produce temporary swings in both weight and mood but no permanent change. As such, chronic dieters might best be advised to abandon their dieting attempts. PMID- 7886193 TI - Female nudity in advertisements, arousal and response: a parsimonious extension. AB - This study extended a 1990 report of LaTour, Pitts, and Snook-Luther by further analysis. Relationships between the key dimensions of High Activation (tension) and General Activation (energy) and ratings of attitude toward the advertisement were analyzed in a test of two hypothetical models performed on ratings by 134 undergraduate business students who responded to the paper-and-pencil tests which operationalized the constructs. In addition, attitude toward the brand was added to the formulation to evaluate the tenability of direct effects of arousal on attitude toward the brand (Ab) and indirect effects "filtered through" attitude toward the advertisement (Aad). Analysis supported the idea that excessive rated tension induced from an erotic advertisement has negative consequences. As predicted, different structural relations between these variables occur under different conditions. PMID- 7886194 TI - When nurses obtain consent for organ donations. PMID- 7886195 TI - Nurse fails to chart call to doctor. Case in point: Morse v. Flint River Comm. Hosp. 450 S.E.2d 253--GA (1994). PMID- 7886196 TI - Legal case briefs for nurses. LA: aggravation of pre-existing condition: eligibility for workers' compensation; GA: covenant not to sue anesthesia group: suit against nurses and hospital not barred. PMID- 7886197 TI - What happens when your patient can't speak English? Case in point: City of Irving v. Pak 885 S.W.2d 189--TX (1994). PMID- 7886198 TI - Proceedings of the 5th International Symposium on Neural Regeneration. Pacific Grove, California, December 8-12, 1993. PMID- 7886199 TI - Hierarchical guidance cues and selective axon pathway formation. PMID- 7886200 TI - Calcium and gene expression. PMID- 7886201 TI - Regulation of neurite outgrowth and immediate early gene expression by patterned electrical stimulation. PMID- 7886202 TI - Nuclear calcium elevation may initiate neurite outgrowth in mammalian neurons. PMID- 7886203 TI - Expression of c-Jun and JunD transcription factors represent specific changes in neuronal gene expression following axotomy. PMID- 7886204 TI - Models of spinal cord regeneration. PMID- 7886205 TI - Functional regeneration and restoration of locomotor activity following spinal cord transection in the lamprey. PMID- 7886206 TI - Spinal cord regeneration in adult goldfish: implications for functional recovery in vertebrates. PMID- 7886207 TI - The lizard spinal cord: a model system for the study of spinal cord injury and repair. PMID- 7886208 TI - Nerve growth factor and neuronal gene expression. PMID- 7886209 TI - Permissive and restrictive periods for brainstem-spinal regeneration in the chick. PMID- 7886210 TI - Repair of connections in injured neonatal and embryonic spinal cord in vitro. AB - A remarkable preparation for studying development and repair is the CNS of the newborn opossum which, removed in its entirety, survives in culture for more than 1 week. In suitable medium, cells continue to divide, mature and reflex activity is maintained. Moreover, nerve fibers grow rapidly, reliably and extensively across lesions made in the spinal cord. Restoration of conduction has been demonstrated by recording electrically; labeled fibres have been observed directly by light and electron microscopy as they traverse the lesion. Similar experiments have also been made in embryonic (E15) rat CNS in culture. Open questions concern the identity of the fibers that traverse the lesion and the specificity of connections that they make with targets. We are now also analysing mechanisms that favor repair in younger opossums and that prevent it in their older siblings. Of particular interest are oligodendrocytes and myelin that start to appear at about 8-9 days after birth. PMID- 7886211 TI - Response of rubrospinal and corticospinal neurons to injury and neurotrophins. PMID- 7886212 TI - Cross-talk between nervous and immune systems in response to injury. PMID- 7886213 TI - Neurotrophins: signals between the nervous and immune systems. PMID- 7886214 TI - Neurotrophins and receptors. PMID- 7886215 TI - Class I and II MHC expression and its implications for regeneration in the nervous system. PMID- 7886216 TI - Cytokines and cytokine-related substances regulating glial cell response to injury of the central nervous system. PMID- 7886217 TI - Immune promotion of central nervous system remyelination. AB - Remyelination by oligodendrocytes is the normal response to injury of the central nervous system following experimental demyelination by toxins and viruses in rodents. By contrast, in immune-mediated myelin disorders such as human MS, Theiler's virus-induced demyelination or EAE, remyelination is incomplete. We have considered two hypotheses to explain why myelin repair is incomplete in these disorders. Hypothesis I is that myelin repair is the normal consequence of primary myelin injury but there are immune factors which prevent its full expression. To test hypothesis I, we depleted T cells in Theiler's virus infected mice with cyclophosphamide or with monoclonal antibodies to CD4, CD8, or immune response gene products (Ia). Enhanced remyelination and proliferation of glial cells was observed in mice depleted of CD4+ or CD8+ T cells. Hypothesis II is that there are immune factors within some demyelinated lesions which, when present, promote new myelin synthesis. We envision these factors to be present in those lesions showing remyelination but absent in those lesions that remain demyelinated. To test hypothesis II, we generated polyclonal immunoglobulins directed against normal CNS antigens. Transfer of immunoglobulins from mice immunized repeatedly with spinal cord homogenate resulted in 4-5-fold enhancement of remyelination in Theiler's virus infected mice. We have also generated a series of monoclonal antibodies directed against normal autoantigens which also promote CNS remyelination. These experiments support the concept that full CNS remyelination is possible in human demyelinating diseases such as MS. Manipulation of the immune response either by inhibiting the function of T cells or by treatment with immunoglobulins (possibly normal autoantibodies) appears to promote remyelination. These experiments provide hope for patients with fixed neurological deficits for whom there are currently no available therapies. PMID- 7886218 TI - Nitric oxide in the central nervous system. AB - 1. The reactions of nitric oxide with superoxide can lead to neurotoxicity through formation of peroxynitrite, and not by NO. alone, at least under our conditions. 2. Transfer of NO+ groups to thiol(s) on the NMDA receptor can lead to neuroprotection by inhibiting Ca2+ influx. These findings suggest that cell function can be controlled by, or through, protein S-nitrosylation, and raise the possibility that the NO group may initiate signal transduction in or at the plasma membrane. 3. The local redox milieu of a biological system is of critical importance in understanding NO actions as disparate chemical pathways involving distinct redox related congeners of NO may trigger neurotoxic or neuroprotective pathways. These claims are highlighted in the CNS by the recent finding that tissue concentrations of cysteine approach 700 microM in settings of cerebral ischemia (Slivka and Cohen, 1993); these levels of thiol would be expected to influence the redox state of the NO group. 4. Finally, our findings suggest novel therapeutic strategies. For example, downregulation of NMDA receptor activity via S-nitrosylation with NO+ donors could be implemented in the treatment of focal ischemia, AIDS dementia, and other neurological disorders associated, at least in part, with excessive activation of NMDA receptors. PMID- 7886219 TI - Reactions of nitric oxide, superoxide and peroxynitrite with superoxide dismutase in neurodegeneration. PMID- 7886220 TI - Regulation by neuroprotective factors of NMDA receptor mediated nitric oxide synthesis in the brain and retina. PMID- 7886221 TI - Target derived and putative local actions of neurotrophins in the peripheral nervous system. PMID- 7886222 TI - Axonal outgrowth and pathfinding. PMID- 7886224 TI - Regulation of growth cone motility by substratum bound molecules and cytoplasmic [Ca2+]. PMID- 7886223 TI - Regulation of events within the growth cone by extracellular cues: tyrosine phosphorylation. PMID- 7886225 TI - Contributions of multiple forms of myosin to nerve outgrowth. PMID- 7886226 TI - Are you using neuronal densities, synaptic densities or neurochemical densities as your definitive data? There is a better way to go. PMID- 7886227 TI - Early developmental patterns and mechanisms of axonal guidance of spinal interneurons in the chick embryo spinal cord. PMID- 7886228 TI - Gonadal hormones as promoters of structural synaptic plasticity: cellular mechanisms. AB - It is now obvious that the CNS is capable of undergoing a variety of plastic changes at all stages of development. Although the magnitude and distribution of these changes may be more dramatic in the immature animal, the adult brain retains a remarkable capacity for undergoing morphological and functional modifications. Throughout development, as well as in the postpubertal animal, gonadal steroids exert an important influence over the architecture of specific sex steroid-responsive areas, resulting in sexual dimorphisms at both morphological and physiological levels. We are only now beginning to gain insight into the mechanisms involved in gonadal steroid-induced synaptic changes. The number of synaptic inputs to specific neuronal populations is sexually dimorphic and this can be modulated by changes in the sex steroid environment. These modifications can be correlated with other morphological changes, such as glial cell activation, that are occurring simultaneously in the same anatomical area. Indeed, the close physical relationship between glial cells and neuronal synaptic contacts makes them an ideal candidate for participating in this process. Interestingly, not only can the morphology and immunoreactivity of glial cells be modulated by gonadal steroids, but a close negative correlation between the number of synapses and the amount of glial ensheathing of a neuron has been demonstrated, suggesting an active participation of these cells in this process. Glia have sex steroid receptors, are capable of producing and metabolizing steroids, and can produce other neuronal trophic factors in response to sex steroids. Hence, their role in gonadal steroid-induced synaptic plasticity is becoming more apparent. In addition, there is recent evidence that this process may involve certain cell surface molecules, such as the N-CAMs, since a specific isoform of this molecule, previously referred to as the embryonic form, is found in those areas of the brain which maintain the capacity to undergo synaptic remodelling. However, there is much work to be done in order to fully understand this phenomenon and before bringing it into a clinical setting in hopes of treating neurodegenerative diseases or injuries to the nervous system. PMID- 7886229 TI - Neural graft augmentation through co-grafting: implantation of cells as sources of survival and growth factors. PMID- 7886230 TI - Electrophysiological and metabolic interactions between axons and glia in crayfish and squid. PMID- 7886231 TI - The high affinity uptake system for excitatory amino acids in the brain. PMID- 7886232 TI - Gene expression and function of interleukin 1, interleukin 6 and tumor necrosis factor in the brain. PMID- 7886233 TI - Does the function of REM sleep concern non-REM sleep or waking? AB - We have hypothesized that REM sleep is functionally and homeostatically related to NREM sleep rather than to waking. In other words, REM sleep rather than to waking. In other words, REM sleep occurs in response to NREM-sleep expression and compensates for some process that takes place during NREM sleep. Under normal conditions, the need for REM sleep does not accrue during waking. The primary basis for this hypothesis is the fact that REM-sleep expression is a function of prior NREM-sleep expression. That is, REM sleep follows NREM sleep within sleep periods, REM-sleep episodes occur at intervals determined by the amount of NREM sleep time elapsed, and total time spent in REM sleep is consistently about 1/4 of prior NREM-sleep time, regardless of how much time is spent in NREM sleep. Our experimental tests of the hypothesis support it. (1) REM-sleep propensity accumulates quite rapidly during a 2-hr interval spent predominantly in NREM sleep. (2) The timing of individual REM-sleep episodes is controlled homeostatically, by accumulation within NREM sleep of a propensity for REM sleep. The NREM sleep-related model of REM-sleep regulation (Fig. 1) explains a number of phenomena of REM-sleep expression, including the frequent and periodic occurrence of REM-sleep episodes throughout sleep periods, that have been accommodated by the waking-related model but are not functionally accounted for by it. In our opinion, the NREM sleep-related model of REM-sleep regulation recommends itself partly by its simplicity. According to the waking-related model, two independent and competing sleep propensities accumulate during waking and are discharged in two distinct sleep states that perform different waking related recovery processes. One behaviour, sleep, is thought to perform two independent and competing functions that alternate at regular intervals. In the NREM sleep-related model of REM-sleep regulation, sleep debt simply reflects a need for NREM sleep. That is, the cerebrally less activated state of NREM sleep enables some form of restoration made necessary by the cerebrally activated state of waking. Periodic occurrence of REM-sleep episodes is explained without postulating an oscillatory mechanism to gate expression of NREM sleep versus REM sleep. In assessing the comparative merits of the waking-related and NREM sleep related models of REM-sleep regulation, one should consider the influence of time worn habits of thought.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7886234 TI - Release-regulating presynaptic heterocarriers. PMID- 7886235 TI - The neuroprotective actions of chlormethiazole. PMID- 7886236 TI - The hippocampus: a biological model for studying learning and memory. PMID- 7886237 TI - Functions of brain-derived neurotrophic factor, insulin-like growth factor-I and basic fibroblast growth factor in the development and maintenance of dopaminergic neurons. PMID- 7886239 TI - [Determinative mechanisms of the developmental fate during ascidian embryogenesis]. PMID- 7886238 TI - [Molecular mechanism of myogenesis]. PMID- 7886240 TI - [AxCAMs and DenCAMs: a novel classification of neuronal cell recognition/adhesion molecules--with special reference to a telencephalon-specific glycoprotein, telencephalin]. PMID- 7886241 TI - [Axonal regeneration in the central nervous system of adult mammals]. PMID- 7886242 TI - [DNA sensor by using a quartz-crystal microbalance]. PMID- 7886243 TI - [A strategy for one week sequencing]. PMID- 7886244 TI - [What is psychoanalysis today?]. PMID- 7886245 TI - [Expert assessment within the scope of legal social determination of the extent of economic responsibility of insurance for analytic psychotherapy]. AB - Expert Opinions and Social Insurance Tribunal Rulings on the Scope of Medical Insurance Cover for Analytic Psychotherapy.--In Germany at present medical insurance cover is more or less automatic for a bone-marrow transplant costing anything up to 100,000 dollars--an operation where the death of the patients is by no means infrequent. In view of this state of affairs it is hard to comprehend the refusal on the part of insurance cover reviewers to approve ongoing cover for analytic psychotherapy beyond the 240-hour limit. In the case presented here, privately financed continuation by some 180 hours demonstrated that this prolongation and intensification of therapy was in fact essential to ensure the success of the treatment. PMID- 7886246 TI - [Response to Gerhard Fichtner's "necessary position" and comments on Michael Schroter's book review]. PMID- 7886247 TI - [Medical confidentiality and scientific research. Comments on the essay by Gerhard Fichtner]. PMID- 7886248 TI - [Divisions in the history of the psychoanalytic movement]. PMID- 7886249 TI - Enterprise bargaining in the private sector. PMID- 7886250 TI - DRG data: the key to good health service management. PMID- 7886251 TI - Primary health care in South Africa. PMID- 7886252 TI - Finally, the 38-hour week.... PMID- 7886253 TI - Polybrominated biphenyl and diphenylether flame retardants: analysis, toxicity, and environmental occurrence. AB - Data on two classes of brominated polyaromatic flame retardants are reviewed with emphasis on analytical aspects, occurrence, fate, and toxicity in the environment. Concentrations of brominated fire retardants are quantified as equivalents of commercial mixtures. Because different congeners behave differently in the environment and show large differences in toxicity, future studies would benefit from the availability of analytical standards of individual congeners. The main environmental properties and mechanisms of toxicity of the PBBs and PBDEs are similar to those of the structurally related PCBs and dibenzodioxins. Although the present concentrations of brominated fire retardants do not yet appear to represent a major environmental risk in marine food chains, their replacement by environmentally less harmful alternatives is recommended. PMID- 7886254 TI - Pesticide residues in olive oil. AB - The attacks of pests and diseases and the presence of weeds make it necessary to apply pesticides to olive trees to ensure crop protection. Residues of these compounds may remain and contaminate the oil produced. For the analysis of pesticide residues in olive oil, the most common methods are multiresidue methods for fatty substrates, based on partitioning between hexane or light petroleum and acetonitrile. Recently, other methods have been applied, such as ready-to-use, disposable minicolumns or direct injection of oil into a capillary gas chromatograph equipped with a precolumn with an oil recovery tank. Although several pesticides are registered in oil-producing countries for use on olive trees, available literature on the level and fate of residues is very limited. However, it is clear that fat-soluble pesticides tend to concentrate in the oil, both after full coverage and bait spraying, and their use close to harvest should therefore be avoided. Because it is sometimes necessary to use such pesticides late in autumn because of their effectiveness in cases of severe attack, residue trials should be carried out to determine the residue concentration in oil and to set a reasonable preharvest safety interval. Data produced by such trials would permit the establishment of MRLs (tolerances) in olive oil to cover cases where the residues, although relatively high, are not of toxicological significance for consumers (risk assessment). Such is the case with corn oil and the fat-soluble insecticide methyl pirimiphos, registered in the U.S. for use on corn. The U.S. EPA tolerance for methyl pirimiphos in corn is 8 mg/kg, whereas it is 11 times higher (88 mg/kg) for corn oil because it is known to concentrate in the oil. Similar provisions for olive oil, based on data from residue trials according to Good Agricultural Practice, the long-term toxicity of each pesticide as expressed by its ADI for man, and olive oil consumption patterns, would facilitate international trade of this commodity. On the other hand, because of the high dietary and health value of olive oil, it is desirable that toxic pesticide residues be kept as low as possible. Therefore, it would be preferable not to rely only on chemical pest control treatments but to develop and apply alternative plant protection techniques such as Integrated Pest Management (IPM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7886255 TI - Transport of organic environmental contaminants to animal products. AB - A large number of chemical contaminants potentially may be present in agricultural environments, leading to exposure of animals and potential residues in animal products. The contamination may be either widespread, as a result of aerial transport of industrial emissions, or localized, as a result of accidental emissions and spills, improper waste disposal, contaminants in useful products, and areas of past use of products now banned. The halogenated hydrocarbons, including the polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and persistent organochlorine insecticides remaining from past use, are the contaminants of most concern. Depending on the degree and pattern of chlorine substitution, these compounds are resistant to degradation and tend to accumulate in the fat of animals and their products. Other classes of environmental contaminants as exemplified by the PAHs, phthalate esters, acid phenolics, and nitrosamines also may occur widely in the environment. These compounds are unlikely to be transported to animal products because the compounds are water-soluble or can be metabolized to water-soluble products, which are excreted in the urine and thus do not bioaccumulate in products such as milk and meat. The points of entry of environmental contaminants into agricultural environments usually are plants and soils. Lipophilic compounds such as the halogenated hydrocarbons are not taken up and translocated by plants. Contamination of plants is mainly a surface phenomenon resulting from aerial deposition of emissions or deposition of compounds volatilized from the surface of contaminated soil. Thus, fibrous roughages used primarily in feeding cattle and other ruminants will be the most important pathway of animal exposure and transport to human foods. The second pathway of animal exposure is by ingestion of contaminated soil while grazing or when confined to unpaved facilities. As in the case of feed sources, cattle is the species most vulnerable to exposure by the soil ingestion pathway under most commercial management systems, but poultry and swine are more vulnerable in those infrequent situations in which these species have access to contaminated soil. PMID- 7886256 TI - [Effects of lyophilization on four biological activities of Bothrops atrox venom (Serpentes: Viperidae)]. AB - Fresh venom was obtained by milking both sexes of adult Bothrops atrox snakes. Four biological activities were studied in both fresh and freeze dried venom: local hemorrhagic in guinea pig skin, proteolytic upon casein (caseinolytic), esterasic upon TAME and fibrinogen clotting activity. All activities were detected in fresh venom: Hemorrhagic (DHM = 0.93, DHR = 9.75 micrograms protein), caseinolytic (0.25 U kunitz/mg protein), esterasic (0.70 U/mg protein) and clotting activity (75.7 U NIH/mg protein). After freeze drying, all the biological activity of B. atrox venom enzymes decreased: hemorrhagic, caseinolytic and clotting activity in 50% and the esterasic activity only in 15%. Our results show that lyophylization decreases several important biological activities in snake venom related to a decrease in the venom enzymatic activities. PMID- 7886257 TI - Contamination of bovine milk with residues of inhibitory substances in Costa Rica. PMID- 7886258 TI - The swarming phenomenon of Clostridium tetani. PMID- 7886259 TI - [Reactivity of sera from Chagas patients to extracts of mexican Trypanosoma cruzi isolates]. AB - An antigenic extract prepared from four different Mexican isolates of Trypanosoma cruzi cultured on BHI (three came from human cases-Agripina, Fidelfa and Ninoa, and other from triatoma-Cocula) were assayed with human sera. ELISA results always were consistent with clinical diagnosis. Sera from patients with a diagnosis of Chagas disease were reactive and non-chagasic sera were negative. Western blot of chagasic sera recognized antigens of molecular weight > 81 kd, 81 kd, 54 kd, 42 kd, and 26 kd. Sera with high OD in ELISA reacted with more peptide bands. The soluble extract antigens prepared from Mexican isolates of T. cruzi and from the Brazilian Y strain have an homogenous and similar reactivity. PMID- 7886260 TI - [The evaluation of diastolic function: isotopes or ultrasound? The isotopic perspective]. PMID- 7886261 TI - [Mortality from ischemic cardiopathy in Spain: the trends and geographic distribution]. AB - INTRODUCTION: In order to obtain epidemiological information for health planification, age-adjusted time series and provincial distribution of ischaemic heart disease mortality have been constructed. MATERIAL AND METHODS: Analysis of time trends includes data from 1901 to 1989. Trends have been identified by linear regression analysis. For the period 1976-1986 age-adjusted and age and sex specific mortality rates have been calculated for each province. 1984 and 1989 levels have been compared to those of the European Union countries. RESULTS: After the sharp rise of the curve in the 50-70 decades, since 1976 mortality falls with an statistically significant negative slope. This change in trends cannot be explained by time variations in prevalence of the main risk factors. Although in many European countries mortality began to fall much earlier, Spain still remains between the lowest mortality rates in Europe. Provinces showing the highest rates are the islands, Andalucia, Badajoz, Murcia, Alicante and Asturias. This clear north-south pattern is maintained after stratifying by age and sex, thus indicating that geographical distribution is related more to environmental or socio-economic factors and to accessibility to qualified health care, than to the geographical distribution of age and sex related risk factors. CONCLUSIONS: Additional studies including other variables are needed to explain these time and spatial variations. Allocation of specialized health care resources can be an effective intervention, mostly in the above mentioned provinces. PMID- 7886262 TI - [The postinfarct prognostic value of right ventricular systolic function]. AB - BACKGROUND: Right ventricular extension of inferior myocardial infarction has been shown to be a predictor of poor prognosis during the acute phase. However, it is not known whether right ventricular dysfunction predicts long term complications. The aim of the present study was to assess whether right ventricular ejection fraction is also a predictor of poor prognosis during the first five follow-up years. METHODS: Ninety-eight consecutive patients (age < or = 65 years) with acute noncomplicated myocardial infarction (49 anterior and 49 inferior) were evaluated before hospital discharge. In all of them the ejection fraction of both ventricles was evaluated with radionuclide ventriculography at rest and during submaximal exercise. All patients were clinically followed up for at least 5 years. The prognostic relevance of right and left ventricular function for the prediction of all complications and severe complications was assessed using univariate and multivariate analysis. RESULTS: After 5 years, 66 patients had 94 complications (angina in 44, heart failure in 21, reinfarction in 10, revascularization procedures in 11, death in 6). In the univariate analysis, resting right ventricular ejection fraction was significantly lower in patients with inferior infarction and severe complications at one year (32 +/- 12% vs 38 +/- 6%, p = 0.03). However, in multivariate analysis only resting left ventricular ejection fraction was predictive of complications at 5 years (odds ratio 5.93, 95% confidence interval = 1.32-26.6). Statistical results did not change when the ejection fraction of both ventricles during submaximal exercise was considered. CONCLUSIONS: Although right ventricular ejection fraction, measured before hospital discharge, is predictive of complications at five years in inferior infarctions, multivariate analysis shows that it does not add prognostic information to the measurement of left ventricular ejection fraction in patients with uncomplicated acute myocardial infarction, either anterior or inferior. PMID- 7886263 TI - [Doppler echocardiographic evaluation of pulmonary hypertension in children]. AB - INTRODUCTION: We analysed the usefulness of Doppler echocardiography to determine the presence and severity of pulmonary hypertension (PH) in children. METHOD: The whole group consisted of 63 patients, 42 with congenital heart disease that underwent cardiac catheterization (32 of whom had PH = study group) and 21 healthy children. These 21 patients and the remaining 10 without PH at cardiac catheterization made up the control group. All children were studied with Doppler Echocardiography to evaluate the pulmonary flow pattern with the sample volume placed in the pulmonary artery trunk, 1 cm distal to the pulmonic valve. The preejection period (PEP), ejection period (EP), acceleration time (AcT), the indexes PEP/EP, PEP/AcT, AcT/EP and the morphologic pattern of the pulmonary flow (type I: with peak flow velocity at midsystole; type II: with peak flow velocity in early systole; type III: with midsystolic notching) were analysed and quantitative parameters corrected according to hear rate by dividing theirs value by the square root of R-R interval. In the hemodynamic study we analysed the systolic (SPAP), diastolic and mean pulmonary artery pressure, and the mean pulmonary pressure/mean systemic pressure ratio (Pp/Sp). We compared the echocardiographic variables in both, study and control groups, and analysed the hemodynamic and echocardiographic correlation between the variables in question. RESULTS: Pattern I of pulmonary flow was associated with absence of PH and pattern II and III with PH (p < 0.001). The best results of quantitative variables were either corrected AcT (AccT) rather less in the study group than in control group (2.89 +/- 0.56 vs 4.05 +/- 0.56 ms, p < 0.001) and PPE/AcT index, 1.28 +/- 0.3 in the hypertensive group and 0.78 +/- 0.16 in the control group (p < 0.001). The best correlation were AcT with SPAP (r = -0.82) and Act with Pp/Sp ratio (r = -0.84). CONCLUSIONS: We consider that pulmonary flow analysed with Doppler echocardiography is a reliable, suitable and non-invasive method to evaluate PH in children. PMID- 7886264 TI - [Cardiovascular pharmacology (IX). Angiotensin-converting enzyme inhibitors in hypertension and heart failure]. PMID- 7886265 TI - [The reversibility of pulmonary hypertension associated with autoimmune hyperthyroidism]. AB - We report the case of a 28-year-old woman in a chronic hemodialysis program, who developed moderate pulmonary hypertension (eco-Doppler assumed pulmonary systolic pressure of 62 mmHg), with right ventricular dilatation (49 mm) in coincidence with a fully symptomatic autoimmune hyperthyroidism. The improvement of thyroid function resulted in a significant regression of pulmonary hypertension (45 mmHg) and normalization of right ventricular size (35 mm). The appearance and reversibility of pulmonary hypertension associated to autoimmune hyperthyroidism have not been described before and, in our patient, it is probably facilitated by other coincident factors that increase cardiac output and, subsequently, pulmonary flow, i.e. anemia and the arteriovenous fistula for hemodialysis. PMID- 7886266 TI - [Acute myocardial infarct and Friedreich's disease]. AB - The association between Friedreich's ataxia and heart disease is well known. Microvascular disease and spasm of coronary arteries have been reported. We report now a patient with the association between this disease and acute myocardial infarction, which raises the hypothesis that it may be related with the already known cardiac abnormalities in this disease. PMID- 7886267 TI - [The usefulness of biochemical markers in detecting myocardial damage associated with a perioperative infarct and heart transplant rejection]. PMID- 7886268 TI - [The evaluation of left ventricular diastolic function by noninvasive methods: isotopic ventriculography versus echo-Doppler]. PMID- 7886269 TI - [The evaluation of diastolic function: isotopes or ultrasound? The echocardiographic perspective]. PMID- 7886270 TI - Persistent GHRH-induced PRL secretion in Cushing's syndrome, obesity and exogenous hypercortisolism. AB - Endogenous Cushing's syndrome, obesity and chronic glucocorticod treatment are characterized by blunted GH secretion. The administration of GHRH is capable of stimulating a small but significant PRL increase in normal subjects. The current study was designed to determine plasma PRL levels in response to GHRH, studied in three different situations characterized by a blunted GH secretion. Obese patients (n = 6) with a weight over 30% of ideal body weight, patients with active Cushing's syndrome, and normal volunteers treated with dexamethasone 22 mg per os over two days before the pituitary challenge were studied. As a control group 18 normal subjects of similar age and sex were studied. GH and PRL was determined at intervals after GHRH (1 microgram/kg). GHRH-induced GH secretion was markedly reduced in patients with obesity, patients with endogenous Cushing's syndrome and volunteers treated with dexamethasone. In contrast, GHRH-induced PRL secretion was not affected in these three clinical situations. In summary, in three situations characterized for an impairment of the somatotroph cell, due to a primary intrinsic defect or to a functional hypothalamic alteration, there is a persistent GHRH-induced PRL secretion, suggesting that prolactin could be released by mammosomatotrophs that function normally in spite of hyposomatotropism. PMID- 7886271 TI - Relation of abnormal composition of lipoproteins to HbA1c levels in non-insulin dependent diabetes. AB - Plasma lipids and VLDL and HDL composition were studied in a control group of 20 non diabetic subjects and in 31 male middle-age patients with non-insulin dependent diabetes treated by oral hypoglycemic agent glibenclamide and a weight maintaining diet. Data for the diabetics were separated based on haemoglobin A1c of less or greater than 7%. VLDL composition abnormalities were more frequent in the diabetic patients with HbA1c of > 7%. VLDL-cholesterol, VLDL-triglycerides and VLDL-phospholipids were high in all diabetics whereas VLDL-apo B increased only in diabetics with HbA1c > 7%. Apo CII and apo CIII levels and also apo CII/apo CIII ratio were also reduced in the diabetic patients with HbA1c levels of more than 7%. Increases in the apo E and apo E/apo C ratio were also seen in the more hyperglycemic diabetics with HbA1c levels > 7%. In contrast apo CII and apo CIII levels and also Apo CII/Apo CIII ratio remained unaltered in diabetic patients with less than 7% HbA1c levels. In these patients increases in the apo E levels were found while the apo E/apo C ratio remained unaltered. All diabetic patients showed increases in HDL-triglycerides and triglyceride/total cholesterol ratio with respect to control. Decreases in HDL-apo AI were also seen in both groups of diabetics, but the HDL-apo AI/HDL-apo AII ratio did not differ from control. PMID- 7886272 TI - Effect of cefepime (BMY-28142) on the hemolytic and bactericidal activity of serum in vivo and in vitro. AB - The present study was undertaken to determine whether cefepime (BMY-28142) could influence the hemolytic and bactericidal activity of serum both in vivo and in vitro. For the in vivo studies, mice (Swiss aged 15 +/- 2 weeks) were studied before and 1, 2, 4, 8, and 12 h after an intramuscular injection of 200 mg/kg of cefepime. Likewise, another group of mice were injected for 7 days with a daily injection of the same dose as before, and sacrificed one hour after the last injection. For the in vitro studies, samples were incubated in the presence and absence of cefepime (1/2, 1/4 and 1/8 MIC against Staphylococcus aureus) (2.5, 1.25 and 0.625 mg/l respectively). The results indicate that cefepime at sublethal concentrations increases the bactericidal activity of serum both in vivo and in vitro against S. aureus, but does not significantly modify the hemolytic activity of the complement. PMID- 7886273 TI - Influence of age and stress from physical activity on the redistribution of lymphocytes. AB - The influence of age and stress on the redistribution of lymphocytes between the intra- and extra-vascular spaces has been studied. Young (12 +/- 4 weeks) and old (68 +/- 6 weeks) mice were made to swim until exhaustion, with and without a previous period of training. Lymphocyte concentration in the blood and in the peritoneal cavity, was evaluated as well as the weight of spleen and thymus in these animals. In parallel, and as an indicator of the level of stress, quantification was made of the serum corticosterone levels and weight as well as the protein, DNA, and RNA content of the adrenal glands. Results indicate that, after being subjected to stress, the young mice present no changes in lymphocyte number in blood or peritoneal cavity. Old mice, however, after acute physical activity, present a greater lymphocyte content in the intravascular compartment, as well as a fall in the peritoneal lymphocyte concentration and spleen weight. The data could indicate that age modifies the response to stress, with an augmentation of lymphocytes in the intravascular compartment at the expense of the extravascular one. PMID- 7886274 TI - Inhibition of D-galactose and L-phenylalanine transport by HgCl2 in rat intestine in vitro. AB - The effect of Hg2+ on galactose and phenylalanine uptake has been studied in rat everted intestinal rings incubated for 2 minutes. The presence of 0.5 mM Hg2+ in the incubation medium inhibited the total galactose uptake from 30% to 40% and that of the phenylalanine about 70%. The inhibition was due to a reduction of galactose transport and Na(+)-dependent phenylalanine transport. Hg2+ inhibited the galactose transport in a non-competitive way, with a Vmax diminution without Km modification. The Na(+)-dependent phenylalanine transport was totally blocked in the presence of 1 mM Hg2+. The washing of the intestinal rings with 5 mM EDTA slightly decreased the inhibition produced by 0.5 mM Hg2+ on phenylalanine uptake whereas it did not modify the inhibition of galactose uptake. However, the inhibition of galactose uptake was completely reversed after washing with 10 mM cysteine. Therefore, phenylalanine transport seems to be more sensitive to HgCl2 than galactose transport. The inhibition of these intestinal transport systems by Hg2+ might be due to its interaction with ligands of the transport proteins located in the luminal membrane of enterocytes. PMID- 7886275 TI - Visual evoked potentials in response to flashes in the cat cortex. AB - A model is presented of visually evoked potentials (VEPs) in the cerebral cortex of cats after binocular stimulation by means of flashes. The VEPs consist of four components: P1, N1, P2 and N2 which appear during the first 100 ms after the stimulation is produced. This model has been found in all the animals used in the experiments and is repeated with small variations at almost all the recording points. After studying the data obtained, a hypothesis is put forward for the possible origin of the four components in the primary visual area. PMID- 7886276 TI - A single dose of a non selective beta-adrenergic agonist increases bone protein synthesis. PMID- 7886277 TI - Effect of continuous light and melatonin on the sexual maturation of the female rat. PMID- 7886278 TI - A long and productive career: Franklin M. Henry--scientist, mentor, pioneer. PMID- 7886279 TI - The effect of trunk angle on power production in cycling. AB - The purpose of this investigation was to determine the effect of three different trunk angles (60, 90, and 120 degrees relative to the ground) on power production of 16 male recreational cyclists (age 20-36 years) when the hip, knee, and ankle angles were controlled. Wingate anaerobic tests were performed on a modified Monark cycle ergometer against a resistance of 85 g/kg of the subjects' body mass (5.0 J/crank rev/kg BM). The order of test conditions was randomly assigned, with a minimum of 24 hr between sessions. A DM MANOVA and post-hoc tests revealed that peak power at the 60 and 90 degree trunk angle was significantly greater than that at the 120 degree angle, and mean power in the 90 degree angle was significantly greater than that at the 120 degree angle. It was concluded that changes in cycling trunk angle may affect peak power and mean power. PMID- 7886280 TI - Effects of physical guidance and knowledge of results on motor learning: support for the guidance hypothesis. AB - The guidance hypothesis (Schmidt, 1991) predicts that the guiding properties of augmented feedback are beneficial for motor learning when used to reduce error, but detrimental when relied upon. Therefore, a heavily guiding form of feedback might be detrimental for learning. In addition, the guidance hypothesis predicts that practice with a high relative frequency of augmented feedback would be detrimental for learning. An experiment is described that crossed two forms of feedback with two levels of relative frequency. Subjects practiced movements to a target with either physical guidance or knowledge of results, and with either a high or faded relative frequency. The high frequency physical guidance condition resulted in the poorest retention, and both high frequency feedback conditions resulted in the least accuracy in transfer. These results provide support for the guidance hypothesis and suggest consideration of the combined effects on learning of the type and relative frequency of augmented feedback and acquisition-test conditions. PMID- 7886281 TI - The effects of erroneous knowledge of results on transfer of anticipation timing. AB - Previous research has shown that erroneous knowledge of results (KR) biased subjects' performance during retention trials for an anticipation timing task (Buekers, Magill, & Hall, 1992). The present experiment extended that work by investigating effects on novel transfer. During acquisition, three groups received either correct KR, erroneous KR, or 50 trials of correct KR followed by 25 trials of erroneous KR, where KR was the anticipation timing error in milliseconds. Erroneous KR was the actual timing error + 100 ms. One day later, subjects performed 15 trials without KR at each of two novel trackway speeds. Results showed that the bias acquired by the All-Erroneous KR condition during acquisition generalized across novel trackway speeds while the Mixed-Correct and Erroneous KR condition yielded a nonsignificant trend toward a response bias. PMID- 7886282 TI - The contextual interference effect for skill variations from the same and different generalized motor programs. AB - Magill and Hall (1990) hypothesized that the contextual interference (CI) effect is found only when task variations to be learned are governed by different generalized motor programs (GMPs). The present experiments examined their hypothesis by requiring subjects to learn variations of a tapping task that had either different (Experiment 1) or the same (Experiment 2) relative timing structure. In each experiment, subjects (N = 36) performed 270 acquisition trials with knowledge of results (KR) in either a blocked or a serial order. One day later, subjects performed 30 retention trials without KR. In data analyses, errors due to parameter modifications were dissociated from errors due to GMP construction to examine which process was responsible for the CI effect. In both experiments, parameter learning created a CI effect while GMP learning failed to produce a CI effect. In the light of these findings, a modification is proposed to the Magill and Hall (1990) hypothesis that takes into account these distinct processes in motor learning. PMID- 7886283 TI - Long slow distance training in novice marathoners. AB - The purpose of this study was to determine the physiological and performance effects of two frequencies and volumes of long slow distance (LSD) training in novice male and female marathoners. Subjects (N = 51) were healthy college students who had not previously run a marathon. They were matched on peak oxygen consumption (VO2peak) into a 6 d.wk-1 (G6) or a 4 d.wk-1 (G4) training group. Both groups trained at 60% to 75% of the heart rate reserve for 15 weeks but G4 trained with 20% less total volume. All groups responded similarly to the training by decreasing percent body fat and maximum heart rate and by increasing fat free mass and VO2peak. All groups significantly decreased the oxygen (O2) cost, lactate level, and heart rate at a submaximal running speed. Within the same gender, performance in the marathon was not different between groups. It was concluded that both training programs prepared subjects equally well to run a marathon. PMID- 7886284 TI - Psychological consequences of athletic injury among high-level competitors. AB - Injury prohibiting continued athletic participation has been hypothesized to have a predictable emotional impact on athletes (Rotella & Heyman, 1986). However, the psychological impact of injury has not been well documented. This study examined the psychological reactions to injury among 343 male collegiate athletes participating in 10 sports. All athletes were assessed using measures of depression, anxiety, and self-esteem during preseason physical examinations. Injured athletes along with matched controls were later assessed within one week of experiencing an athletic injury and 2 months later. A 4 x 3 (Injury Status x Time of Testing) repeated measures multivariate analysis of variance (DM MANOVA) revealed that injured athletes exhibited greater depression and anxiety and lower self-esteem than controls immediately following physical injury and at follow-up 2 months later. These findings supported the general observation that physically injured athletes experience a period of emotional distress that in some cases may be severe enough to warrant clinical intervention. PMID- 7886285 TI - Psychosocial predictors of goal orientations in youth soccer. AB - Little is known about the nature of task and ego orientations that are key motivation constructs. The purpose of this study, therefore, was to examine the extent to which perceived social, contextual, and personal factors predicted the goal orientations of youth sport participants. The sample consisted of 166 male and female adolescent soccer players, who completed self-report measures at the end of a 7-week competitive season. A canonical correlation analysis revealed that the set of predictor variables accounted for 24% of the variance in player goal orientations. Higher scores on perceived soccer competence, perceived parent task orientation, and particularly perceived parent ego orientation were primarily associated with higher scores on player ego orientation. In addition, higher scores on perceived soccer competence, perceived parent task orientation, and perceived mastery climate, as well as lower scores on perceived performance climate, were associated with a higher level of player task orientation. These findings are interpreted and discussed in terms of future research directions. PMID- 7886286 TI - The reporting and analysis of research findings for within-subject designs: methodological issues for meta-analysis. PMID- 7886287 TI - The relationship of self-efficacy and perceived well-being to physical activity and stair climbing in older adults. PMID- 7886288 TI - Perceived exertion and affect at varying intensities of running. PMID- 7886289 TI - The relative age phenomenon in sport: a replication and extension with ice-hockey players. PMID- 7886290 TI - A preliminary study of misclassification of blood cholesterol levels in an adolescent population. PMID- 7886291 TI - Physiological effects of deep water running following a land-based training program. PMID- 7886292 TI - XXV Congress of the International Society of Hematology. April 17-21, 1994, Cancun, Mexico. Proceedings and abstracts. PMID- 7886293 TI - Transfusion medicine 1994. PMID- 7886294 TI - Morphology in hematology. PMID- 7886295 TI - Chronic myelogenous leukemia--update and future directions. PMID- 7886296 TI - Molecular biology of leukemia and lymphoma. PMID- 7886297 TI - Hereditary hemorrhagic disorders. PMID- 7886299 TI - Minimal residual disease in hematologic malignancies. PMID- 7886298 TI - Gene therapy in hematology. PMID- 7886300 TI - Thrombocytopenias and thrombocytopathies. PMID- 7886301 TI - Hemolytic anemias. PMID- 7886302 TI - Molecular biology glossary. PMID- 7886303 TI - Adult acute leukemia. PMID- 7886305 TI - The human genome project. PMID- 7886304 TI - Biology and therapy of childhood acute lymphoblastic leukemia. PMID- 7886306 TI - Clinical use of hematopoietic growth factors. PMID- 7886307 TI - Retroviral diseases in hematology. PMID- 7886308 TI - Myeloma and related disorders. PMID- 7886309 TI - Bone marrow transplantation: past, present and future. PMID- 7886311 TI - Molecular biology of cancer, virus and HLA typing. PMID- 7886310 TI - Chronic lymphoproliferative disorders. PMID- 7886312 TI - The study and treatment of the myelodysplastic patient. PMID- 7886313 TI - Monoclonal antibodies in hematology. PMID- 7886314 TI - Hodgkin's disease. PMID- 7886315 TI - Biotherapy in hematology: the next decade. PMID- 7886316 TI - Non-Hodgkin's lymphoma: treatment of large cell lymphomas. PMID- 7886317 TI - Hereditary and acquired thrombophilia. PMID- 7886318 TI - Gastric alkalinization does not increase the risk of pneumonia in critically ill patients. AB - Nosocomial pneumonia remains an important determinant of hospital-acquired morbidity and mortality. Although therapy designed to prevent stress-induced gastritis has been effective at relieving upper gastrointestinal (GI) bleeding, the use of agents (histamine-2 receptor antagonists, antacids) that raise gastric pH have also been implicated as increasing the incidence of nosocomial pneumonia. Examination of two recently published meta-analyses investigating the role of gastric pH and nosocomial pneumonia and several individual studies show that raising gastric pH does not increase the incidence of nosocomial pneumonia. Importantly, those clinical trials that purport to show that raising gastric pH increases the incidence of nosocomial pneumonia have not been blinded studies and have failed to control for sites of enteral feeding and volume. Taken together, analysis of several clinical trials finds no compelling evidence for the concept that gastric alkalization increases the evidence of nosocomial pneumonia. Given the methodological flaws incurred in several previous studies, the optimal approach for preventing nosocomial pneumonia while preventing stress gastritis induced upper (GI) bleeding remains to be identified. PMID- 7886319 TI - Effect of route of feeding on the incidence of septic complications in critically ill patients. AB - The increased risk of septic complications accompanying severe illness and injury is compounded by the presence of malnutrition. Total parenteral nutrition (TPN) has been used extensively to prevent or rectify this problem. Although enteral nutrition is frequently more difficult to administer, a growing body of laboratory and clinical research shows a significant reduction in the incidence of secondary infection with its use. The mechanism proposed is that the enteral route helps maintain the gut barrier, decreasing passage of bacteria and other toxins. Translocation of these products has been implicated as a cause of nosocomial infection and organ failure. Therefore, when possible, the use of the enteral route of nutrition should be part of the overall approach to the care of the critically ill or injured patient. PMID- 7886320 TI - Effect of manipulating dietary constituents on the incidence of infection in critically ill patients. AB - Nutrition status has major implications for the incidence of infectious complications in critically ill patients. Providing macronutrients and micronutrients in appropriate amounts consistent with the metabolism present during the inflammatory response can significantly reduce the incidence of infectious complications. Current data would indicate that the enteral route of nutrition is more effective in this regard when it is used within 3 to 4 days after injury. The composition of the nutrition formulation is also an important factor in influencing the incidence of infectious complications. Avoiding excess calorie administration, administering restricted amounts of omega-6 polyunsaturated fatty acids, and promoting nitrogen equilibrium are all important aspects of nutrition administration that promote the reduction in infectious complications. Despite these effects, infectious complications remain a common problem in critically ill patients. Based on the anti-inflammatory and lymphoproliferative properties of specific nutrients, enteral products have been formulated with increased amounts of these nutrients. The results of current studies with these products indicate a further reduction in infectious complications and length of hospital stay. PMID- 7886321 TI - Adjunctive human growth hormone therapy in nutrition support: potential to limit septic complications in intensive care unit patients. AB - A large number of studies suggest that growth hormone (GH) modulates immune cell number and function. For example, GH administration in vitro or in animal models enhances antibody synthesis, increases T-lymphocyte proliferation, augments cytotoxic activity of natural killer cells, up-regulates priming of peritoneal and alveolar macrophages, and increases survival rates after infectious challenge. Similar effects on immune cells have been observed with insulinlike growth factor I (IGF-I), a major mediator of GH's anabolic actions. In critically ill patients, the administration of recombinant human GH improves nitrogen and mineral retention, enhances protein synthesis, and reduces urea generation. However, only limited data are available on the modulation of immune function and infection rates with GH treatment in catabolic patients. Limited studies in burn patients have shown improved wound healing and shortened hospital stay with GH therapy. Growth hormone was recently shown to improve cell-mediated immune responses and to maintain serum immunoglobulin concentrations after abdominal surgery in clinically stable patients. The immunomodulatory effects of GH administration may potentially limit septic complications in the intensive care unit setting. However, controlled studies in well-defined patient groups are needed to evaluate the potential beneficial effects of GH on immune function and infection risk in critically ill patients. PMID- 7886322 TI - The effect of nutrition on gastrointestinal barrier function. AB - The tightly adherent monolayer of epithelial cells that line the luminal side of the intestine provides a dynamic and highly regulated barrier to the passive transport of macromolecules. The presence of both nutrients and microbes within the gastrointestinal lumen impose a dichotomous task to this epithelial barrier. Several lines of evidence suggest that conditions created in modern intensive care units (ICUs) dysregulate the discriminatory function of the epithelial barrier. Alterations in intestinal barrier function may result in permeation of autotoxic macromolecules of immense size and diversity that normally reside in the gut lumen. It is becoming increasingly recognized that artificial nutritional support of the critically ill patient may result in significant alterations in epithelial barrier function. The causes and consequences of diet-induced alterations in the gastrointestinal barrier will be discussed. Future strategies in the development of more physiological diets for the critically ill will likely involve the addition of neural, hormonal, and growth factors as stimulants for enhancement of barrier function. PMID- 7886323 TI - Effect of critical illness on microbial translocation and gastrointestinal mucosa permeability. AB - It has been hypothesized that the barrier function of the gastrointestinal tract is deranged in patients with trauma, sepsis, or other critical illnesses. Derangements in intestinal barrier function might lead to bloodstream invasion by gut-derived microbes and/or activation of inflammatory cells in the submucosa of the intestine or within the liver. Activated immune cells are capable of releasing a number of inflammatory mediators, including eicosanoids and cytokines, which have been implicated in the pathogenesis of the multiple organ dysfunction syndrome (MODS). Thus, gut-barrier dysfunction might be primary factor leading to MODS in patients with critical illness. Two distinct forms of gut-barrier dysfunction have been described. The first, called translocation, appears to a transcellular process, whereby particulate antigens, including viable microbes, are transported across enterocytes into the submucosal compartment. The second is an increase in the paracellular permeability of the intestinal epithelium, which permits increased transmucosal absorption of water soluble macromolecules. Pathological increases in both translocation and permeability occur in a number of animal models of critical illness. Moreover, a number of studies have documented that intestinal permeability is increased in humans with trauma, sepsis, burns, or other serious, acute medical problems. Nevertheless, convincing data to establish a causal link between gut-barrier dysfunction and organ failure in humans are lacking, and the importance of translocation and/or mucosal hyperpermeability on the development of MODS in patients remains to be elucidated. PMID- 7886324 TI - Out-patient surgery--a survey of anaesthesia care in a university hospital. AB - This study was done at the Linkoping University Hospital, Sweden, to assess the quality of care given to patients undergoing outpatient anaesthesia. A questionnaire was given to all adult patients (> 15 years old) immediately on admission to the outpatients' surgical ward and the patients were asked to answer all the questions, if necessary with the help of an attending nurse. Another questionnaire was given to the patients in the post-operative ward immediately prior to their being discharged home. Analyses of results indicate that although most patients were satisfied with the care offered at the outpatient surgical unit, 50% requested, but were not given, anxiolytic premedication before the operation. A majority of these were women undergoing gynaecological operations. Twenty per cent of the patients complained of post-operative pain that was poorly managed. Drowsiness (12%), headache (10%), and sore throat (8%) were common complications following general anaesthesia. In contrast, patients who had regional or local anaesthesia had an extremely low incidence of complications. Almost one-third of the patients were discharged without a responsible person accompanying them home and 25% were alone at home during the first 24 hours. Of the patients who went home alone, most either walked, cycled or took the bus, but 4% actually drove home after the operation. In our opinion more stress should be laid on patient information before the operation and better methods to relieve preoperative anxiety should be used whenever indicated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886325 TI - Drug consumption among elderly--a four-year study. AB - The aim of the study was to analyse whether a radical structural change in the provision of care for the elderly, including changes in the pattern of drug administration, might influence drug consumption among residents in a Danish nursing home. A comprehensive reorganization of the care of the residents took place in the mid-1980s. The general approach to self-care, with greater autonomy and influence over one's own life was also disseminated to the area of administration of medication. Previously the nurses had been responsible for this area but a new model was introduced in 1986 in principle permitting all residents to be in charge of their own medication. The study was carried out as a survey over four consecutive years from 1985 to 1988, and included 48 residents in a nursing home of whom 24 participated in all four surveys. A minimum of drugs were administered immediately after the change in regimen. Although a slight increase was recorded in the subsequent years, the level of drug consumption did not reach pre-intervention levels. The total number of regularly administered drugs per day in survey 1 averaged 4.6 drugs/person. In survey 2 this had decreased to average 3.6 (p < 0.05). PMID- 7886326 TI - Physiotherapeutic treatment in out-patient psychiatric care. AB - The present paper aims at describing historical features, developmental trends and key concepts in psychiatric physiotherapy (PPT). PPT was offered as an additional treatment to conventional psychiatric care and the aim was to examine the possibility of carrying out PPT with ten unselected patients (n = 10) in an out-patient psychiatric clinic. Symptoms presented: anxiety and phobic states, depression and crisis reactions. The purpose of four individual sessions was to stimulate curiosity and offer exercises concerning body-mind interactions. In examination of data qualitative research methods were used. All patients accepted the offer of PPT and participated in all sessions. Nine reported great or moderate symptom reduction. Of greatest importance for relief of symptoms was the patient's level of 'engagement'. PPT implies physical proximity and an encounter on an existential level. The impact of a complementary physical approach in psychiatric care needs to be further elucidated. PMID- 7886327 TI - Basic research in caring science. PMID- 7886328 TI - Historical, cross-cultural, biological and psychosocial perspectives of ageing and the aged person. AB - This paper analyses the concept of ageing and old age from various perspectives. From a historical perspective, people in Antiquity and the Middle Ages explained the ages of man in different schematic terms, related to the physical causes for the processes of human growth and decline, or related to daily, annual or historical time. From a cross-cultural perspective, the predominant view has been that older adults in developing societies were better situated socially and psychologically than their counterparts in developed societies. The process of ageing can be seen from separate biological, psychological and social perspectives. Regarding the individual aged person, these mutually interactive processes, must be considered together, along with the cultural conditions and historical times in which they occur. Increased awareness of the positive contributions to modern society made by the aged as upholders of cultural heritage and traditions may help to counteract the derogatory of references to the elderly as 'the rising tide', associating this group of the population with heavy financial burdens on society. PMID- 7886329 TI - Involvement of maternity and health care staff in breast-feeding. AB - The prerequisites of the staff for their interest and concern in working with questions related to breast-feeding have been studied by questionnaires which were answered by 133 nurses at pregnancy care centres, child health centres and maternity wards. The intention was to identify possible obstacles for the staff in supporting the mother's breast-feeding. In spite of extensive experience and positive attitudes to breast-feeding, about half of the staff found it difficult to work with these questions and to give enough support. The most common reasons for this fact were insufficient knowledge about breast-feeding, few possibilities for further training and a heavy workload. It was also evident that some routines need to be corrected. For instance, information about breast-feeding was provided late during pregnancy, the fathers were infrequently engaged and the communication between the departments was limited. A reorganization of the staff's working routines and their continuous further training in issues related to breast-feeding are recommended. PMID- 7886330 TI - The 'good mother'--a comparative study of Swedish, Italian and American maternal behavior and goals. AB - This paper is based on a comparative, psychologically informed ethnographic study of maternal goals and infant care during the first year of life for 20 mothers and infants in each of three Western settings: Stockholm, Sweden, outside Rome, Italy, and suburban Boston, in the United States. Two research questions were posed to consider cultural ideas and ideals about mothering; How was the 'good mother' defined? How did sample women themselves, mother? Research hypotheses were that definitions of a good mother would be culture-specific with minimal within-culture variance. Furthermore, the frequency of maternal behaviors would also exhibit culture specific patterns. Research methods included event based behavioral observations of infant-caregiver interactions in the home, daily routine questionnaires, maternal attitude interviews, and ethnographic observations of community and family life. Research hypothesis were confirmed. Results revealed culture-specific variation in conceptions of the 'good mother'. Cultural differences were reflected in the short- and long-term goals which the sample women described for their children. Patterns of infant care, in turn, were consistent with the cultural values expressed, as well as the cultural norms of social interaction. PMID- 7886331 TI - Quality by selection and purchasing of urinary incontinence aids-- perceptions of nurses and administrators. AB - In a qualitative-quantitative study, differences in the perceptions of nurses and administrators (admin's) dealing with the purchasing of urinary incontinence (UI) aids were studied by means of interviews with a cognitive and emotional approach. Various aspects of purchasing were concentrated on: cooperation, strategy, competence, costs, measures, and decisions, as well as quality in the selection of aids in order to improve quality of care and achieve better economy. The findings show a continued need for centrally coordinated purchasing (CCP), not least related to the European Community, and also problems of integration. Due to the decentralization process, the nurses perceived a need for more education in overall business strategies in order to underline more constructively their caring and patient-oriented opinions. The admin's experienced uncertainty in their purchasing activities caused by the absence of purchasing policies and lack of knowledge of new demands and routines. PMID- 7886332 TI - Impact on health care consumption of an experimental daycare intervention. AB - The purpose of the present study was to assess the impact on health care utilization of a controlled intervention programme for geriatric daycare patients. Sixty-five patients referred to daycare were allocated to an intervention and control group respectively. The 12-week programme was added to the ordinary daycare agenda and was designed in active collaboration with the patients in order to counteract passivity and enhance active patient involvement. Evaluations were made before and after 6 and 12 weeks of intervention, as well as 3 and 9 months after the conclusion of the programme. No extra resources were allocated to either the intervention or the control group. During the intervention period there were no changes in the utilization of home care for either group during the whole study period. Noticeably, there was a significant difference in the number of patients readmitted to hospital between the intervention and control groups (13/33 and 21/32 respectively). There was also a significant difference in favour of the intervention group concerning mean length of hospital stay (22.1 and 61.9 days respectively). The mean corresponding saving for each 12-week intervention patient during a one-year follow-up was calculated at 57,500 SEK. Even if our calculations are tentative and do not cover all aspects of the total cost, they indicate the importance of further studies of elderly patients discharged from daycare units and institutional settings. PMID- 7886333 TI - Visual impairment related to cognition and loneliness in old age. AB - Reported problems in visual acuity were examined as determinants of loneliness experienced by community dwelling people with either impaired or unimpaired cognition. The Mini-Mental State Examination (MMSE) was used as a screening instrument to form a cognitively-impaired (MMSE 20-23/30) and a cognitively intact group (MMSE 28-30/30). A total of 147 subjects took part in the study and were examined by an optometrist. Subjects with intact cognition tended to report visual problems more often than subjects with cognitive deficits. One out of two subjects had slight visual impairment, in both cognitive groups. After acuity had been optimally corrected, six to seven out of ten subjects' visual acuity did improve. In a multiple regression analysis, higher MMSE score and visual improvement were significantly related to lower levels of self-reported loneliness among the elderly with their cognition intact, but not among the subjects with impaired cognition. PMID- 7886334 TI - [Colorectal cancers. Postoperative surveillance and complications]. PMID- 7886335 TI - [Colorectal cancers. Preparation for surgery and postoperative surveillance. Nursing care]. PMID- 7886336 TI - [Colorectal surgery. Role of the operating room nurse]. PMID- 7886337 TI - [The colorectal cancers]. PMID- 7886338 TI - [Cancer of the lower rectum]. PMID- 7886339 TI - [The male urethra and perineum. Anatomical basis for male urethral catheterization]. PMID- 7886340 TI - [Colorectal neoplasms. Anatomo-clinical aspects]. PMID- 7886341 TI - [Treatment of colorectal cancers]. PMID- 7886342 TI - [Detection, evaluation and care of pain. The nurse's role]. PMID- 7886343 TI - [Pain in emergencies]. PMID- 7886344 TI - [Pain connected to examinations and movements]. PMID- 7886345 TI - [Pain in the operating room]. PMID- 7886346 TI - [Postoperative pain]. PMID- 7886347 TI - [Neurogenic pain]. PMID- 7886348 TI - [Drugs against pain]. PMID- 7886349 TI - [Prevention of chronic pain]. PMID- 7886350 TI - [Acute pain in surgery]. PMID- 7886351 TI - [Physiology of pain]. PMID- 7886352 TI - Sickle cell trait and sudden death. PMID- 7886353 TI - Sudden death in athletes. PMID- 7886354 TI - Energetics of competitive swimming. Implications for training programmes. AB - An analysis of the mechanics and energetics of swimming reveals that different factors play key roles in success in competitive swimming events. Knowledge of these performance factors will help the development of optimal training programmes, especially when their relative importance can be identified. One approach to doing this is to evaluate the energy cost of swimming and the energy generating systems that cover these costs. It appears that the rate of energy expenditure is related to the velocity, the gross efficiency, the propelling efficiency and a drag factor. Energy is generated by aerobic and anaerobic processes. A balance should exist between the energy necessary to swim a distance in a certain time and the total energy available in this time from the energy producing system. This balance was used to predict the performance times over difference distances and to predict the effect of a 10% increase in the aerobic capacity, the anaerobic capacity or the propelling efficiency on the performance times, while keeping all other factors constant. The 10% increase in propelling efficiency resulted in both a reduction in time over the short distance as well as an improvement in performance over the long distance which was superior to the gains found when increasing the maximal aerobic or anaerobic power by 10%. It is concluded that for an optimal use of training time and for an optimal use of the capacities of the swimmer, it seems important to determine both the mechanical parameters (technique, drag) and the parameters describing the energy production. By determining the weak and strong points of competitive swimmers, the optimal training distances and what performance factors are the weakest and most likely to improve with training can be determined. PMID- 7886355 TI - The effectiveness of psychological interventions in competitive sport. AB - The use of psychological interventions in competitive sport to enhance performance has become increasingly popular. However, the effectiveness of these interventions has been questioned by some sports psychologists. In general, educationally-based psychological interventions have produced significant increases in performance. Specifically, it was found that 38 of the 45 studies examined (85%) had found positive performance effects, although causality could only be inferred in 20 of these studies. These interventions could be classified as relaxation-based, cognitive, cognitive-behavioural or behavioural in nature. Although general support was provided for the effectiveness of psychological interventions in competitive sports, a number of methodological shortcomings limit the application of the findings. For example, future intervention research in competitive sport should employ more detailed manipulation checks, include follow-up assessments beyond a mere post-test, include placebo-control groups to control for expectancy effects and include more diverse samples. In addition to the empirical intervention research, recent research employing qualitative methodologies has greatly added to our understanding of the types of interventions and what type of sport psychology consultants most positively affect performance enhancement, as well as the personal growth of athletes. Continued quantitative and qualitative research needs to be conducted so that a better understanding is gained of how to conduct psychological interventions with athletes that will enhance performance as well as personal growth. PMID- 7886356 TI - Kidney function during exercise in healthy and diseased humans. An update. AB - Exercise induces profound changes in renal haemodynamics and protein excretion. The rate of ultrafiltration across the glomerular capillary is determined by the imbalance between the transcapillary hydraulic and colloid osmotic pressure gradients. Despite a major reduction in the renal plasma flow, the filtration fraction can double with maximal exercise, preserving the transfer of metabolites or substances through the glomerulus. Tubular processes and excretion rates are modified by exercise. Despite large increases in plasma lactate during strenuous exercise, renal excretion plays a limited role in lactate metabolism. Apparently, the mechanism of transcellular transport of lactate is saturated during severe exercise. Urea reabsorption is enhanced during prolonged exercise, and this process may act to limit the dehydration of an individual. As uric acid transport is also carrier-mediated, it appears that there is no saturation of the carrier system during prolonged exercise. Postexercise proteinuria is directly related to the intensity of exercise rather than to its duration. This excretion of excess proteins is a transient state with a half-time decay of about 1 hour. The increased clearance of plasma proteins suggests an increased glomerular permeability and a partial inhibition of tubular reabsorption. Studies suggest that exercise decreases the glomerular electrostatic barrier and facilitates transfer of macromolecules. Postexercise proteinuria appears to be age-dependent. Nephropathy is a common observation in the diabetic patient. In young and adult diabetic patients, exhaustive physical exercise does not provoke an enhanced dysfunction of the kidney to what is already found in healthy individuals. Heart and kidney transplant patients have a lesser postexercise proteinuria as compared with healthy individuals. PMID- 7886358 TI - [What is your diagnosis? Serous cystadenoma of the pancreas tail with extensive necrosis and fresh post-traumatic bleeding]. PMID- 7886357 TI - Common rugby league injuries. Recommendations for treatment and preventative measures. AB - Rugby league is the main professional team sport played in Eastern Australia. It is also very popular at a junior and amateur level. However, injuries are common because of the amount of body contact that occurs and the amount of running that is required to participate in the game. Injuries to the lower limbs account for over 50% of all injuries. The most common specific injuries are ankle lateral ligament tears, knee medial collateral and anterior cruciate ligament tears, groin musculotendinous tears, hamstring and calf muscle tears, and quadriceps muscle contusions. Head injuries are common and consist of varying degrees of concussion as well as lacerations and facial fractures. Serious head injury is rare. Some of the more common upper limb injuries are to the acromioclavicular and glenohumeral joints. Accurate diagnosis of these common injuries using appropriate history, examination and investigations is critical in organising a treatment and rehabilitation plan that will return the player to competition as soon as possible. An understanding of the mechanism of injury is also important in order to develop preventative strategies. PMID- 7886359 TI - [Surgical therapy in unstable angina pectoris]. AB - In order to assess the value of surgical revascularization of coronary arteries in patients with unstable angina pectoris, a series of 551/3397 consecutive patients belonging to New York Heart Association (NYHA) class IV was investigated. Fulfillment of at least two of the following criteria is mandatory for diagnosis unstable angina pectoris: slightly increased CK (< 300 IU/l), modified ECG at rest (decreased ST-T, increased ST), therapy-resistant post infarction angina, therapy-resistant angina at rest, increased severity, duration or frequency of angina attacks within the last three months, insufficient therapeutic response. Patients with acute myocardial infarction were excluded from analysis. 362/551 patients out of the investigated cohort fulfilled criteria of unstable angina pectoris NYHA class IV; in 189/551 patients, criteria of stable angina pectoris NYHA class IV were fulfilled (controls). The mean follow up period for these patients was 72 +/- 33 months (24 +/- 144 months). There were no differences regarding age, percentage of patients with three vessel disease, ejection fraction of the left ventricle and of cardiogenic shock. The mean number of aortocoronary grafts was 3.8 +/- 1.3 in patients with unstable angina, compared to 3.4 +/- 1.5 in patients with stable angina pectoris (p < 0.05). An intra-aortic balloon pump had to be applied in 8% of patients with unstable angina compared to 3% in stable angina. A mortality of 2% within 30 days of surgery was registered in unstable compared to 3% in stable angina pectoris (n.s).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886360 TI - [Long-term prognosis in unstable angina]. AB - The expression unstable angina pectoris covers a wide range of clinical symptoms with different pathogenetic mechanisms and clinical outcome. Several forms of unstable angina pectoris, in particular progressive angina pectoris (crescendo angina) with chest pain at rest in a previously asymptomatic patient, progressive angina pectoris with chest pain at rest in a previously symptomatic patient, and chest pain at rest of at least 15 min duration without obvious trigger mechanisms have been distinguished. In simpler terms: one may also distinguish angina pectoris of recent onset, crescendo angina, and acute coronary insufficiency. Four risk factors appear to determine the prognosis in these patients: exercise induced angina pectoris, multiple episodes of chest pain before hospitalization, electrocardiographic changes, and recurrent angina pectoris during hospitalization. Acute coronary insufficiency and nontransmural infarction have initially better prognosis than transmural infarction; however, recurrent cardiac events are more frequent in patients with nontransmural infarction, particularly in the elderly with persistent ECG changes, cardiac decompensation, and infarct extension. Unstable angina pectoris and myocardial ischemia after myocardial infarction are generally associated with a poorer prognosis. In contrast, recurrence of angina pectoris after PTCA (within the first six months) is most commonly due to restenosis and hence prognostically not of great importance. Unstable angina pectoris after coronary bypass surgery, however, is a prognostically unfavourable sign. Prognosis in patients with Prinzmetal angina is determined by the extent of coronary disease. In summary, long-term prognosis in patients with unstable angina pectoris depends heavily on the clinical presentation and the previous clinical history of the patient. PMID- 7886361 TI - [Interventional therapy in unstable angina pectoris]. AB - The presence of unstable angina points to the severity of the culprit lesion, but it does not necessarily inform about the extent of coronary artery disease. Coronary angiography should be performed as soon as possible, with the exception of very old patients. If the lesion identified as the cause of unstable angina is amenable to coronary angioplasty (PTCA), the latter can be performed immediately. However, in patients with unstable angina due to an unstable plaque (fissured atheroma with partial thrombosis), acute occlusions occur more often than with routine PTCA, leading to higher perinterventional infarction and death rates and increased need for emergency bypass surgery. In cases with large intracoronary thrombi that are not completely occlusive, preliminary therapy with heparin for a few days or a fibrinolytic agent for a few hours may be wise to diminish the risk of acute vessel closure after PTCA. Sufficient clearing of the thrombus by these measures obviating the need for further interventions may occur occasionally. The point in time of coronary angiography and PTCA in unstable angina is controversial. Medical stabilization may be tried, and it appears that pretreatment with heparin and aspirin may decrease the high complication rate typical for PTCA in the acute phase. On the other hand, PTCA should not be postponed for too long, because of the risk of intercurrent infarction. PMID- 7886362 TI - [Unstable angina pectoris: coagulation disorder and its therapy]. AB - The initiating event in unstable angina is plaque rupture. It triggers platelet activation and aggregation, leading to the formation of an intracoronary thrombus, which can be detected on autopsy, angiography, and by fiber-optic coronary angioscopy. Biochemical markers of platelet and thrombin activity are usually increased and support the pathophysiologic role of coronary thrombosis in unstable angina. Aspirin and heparin have been shown to be effective, whereas thrombolytic therapy has no beneficial clinical effect. Newer specific antithrombotic drugs (hirudin, hirulog) and GPIIb/IIIa platelet receptor inhibitors are being tested in clinical trials and seem to provide a new dimension for the treatment of acute coronary syndromes. PMID- 7886363 TI - [Physical exercise and osteoporosis]. PMID- 7886364 TI - [Calcium and osteoporosis]. PMID- 7886365 TI - [Prevention of osteoporosis by estrogens]. PMID- 7886366 TI - [The treatment of established osteoporosis]. PMID- 7886367 TI - [Osteonecrosis of the femoral condyle. Case reports of 17 patients and literature review]. PMID- 7886368 TI - [Pigmented villonodular synovitis of the hip]. PMID- 7886369 TI - [Sternoclavicular septic arthritis]. PMID- 7886370 TI - [Synovial osteochondromatosis of the hip. Various considerations apropos of a case]. PMID- 7886371 TI - [Churg-Strauss syndrome]. AB - Allergic granulomatosis and angiitis (Churg-Strauss syndrome) is characterized by a systemic vasculitis in the context of bronchial asthma and eosinophilia. Pathologically, there is a necrotizing vasculitis of small arteries and veins with extravascular granulomas, infiltration of vessels and perivascular tissue with eosinophilia. Pulmonary, peripheral nervous system, cardiovascular and cutaneous manifestations are most frequently encountered. Renal failure and high blood pressure are more rare. These features, within the setting of bronchial asthma and eosinophilia, differentiate Churg-Strauss syndrome from polyarteritis nodosa. Steroid associated to cyclophosphamide have considerably improved the prognosis and risk of relapse. PMID- 7886372 TI - [School accidents]. PMID- 7886373 TI - [Breakfast: evaluation of a health activity at school]. PMID- 7886374 TI - [Surgical activities at the Can Tho Hospital (Vietnam)]. PMID- 7886375 TI - [Maternal and infant health program of Sikasso (Mali) of the IAMANEH Society (International Association of Maternal and Child Health): an original model of integrated cooperation]. PMID- 7886376 TI - [Should one prohibit chlorine?]. PMID- 7886377 TI - [Prevention of osteoporosis and role of densitometry]. AB - Osteoporosis is a major public health problem in countries with aging populations, resulting in excess morbidity and mortality. Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and micro architectural deterioration of bone tissue, with the consequent increase in bone fragility and susceptibility to fractures. Therefore, the bone loss that precedes fractures is a continuous process that is often mostly irreversible in the aging. The most efficient method of preventing fractures is the prevention of bone loss. The measurement of bone mass and other skeletal characteristics can effectively identify women at high risk for fractures. The measurement of bone mass which can be carried out by osteo-densitometry is now widely available. It is the only clinical data that can provide accurate assessment of individual fracture risk. Treatments exist that will preserve bone mass and presumably reduce fracture risk; therefore there is a place for screening of patients at high risk of fractures. Many studies have shown recently that a reduced bone mass (at least 1 standard deviation below normal) was associated with a more than 100% increased risk of fracture. Thus the initial assessment of bone mass can be used to estimate future fracture risk and to start prevention measures for high risk patients. Primary prevention can be initiated during the adolescence to optimize peak bone mass. Later in life, secondary prevention can prevent excessive bone loss and more specific treatments can prevent postmenopausal and age related bone demineralization. Strategies of prevention should be promoted and validated as general health care strategies. PMID- 7886378 TI - Contractile properties of skeletal muscle fibers in relation to myofibrillar protein isoforms. PMID- 7886379 TI - Molecular chaperones and intracellular protein translocation. PMID- 7886380 TI - Heteroreceptor-mediated modulation of noradrenaline and acetylcholine release from peripheral nerves. PMID- 7886381 TI - Hexokinases. PMID- 7886382 TI - [Information and soundness: a true disaster]. PMID- 7886383 TI - [A vignette on time]. PMID- 7886384 TI - [Women and delivery in Nicaragua. Collettivo delle Donna di Matagelpa]. PMID- 7886385 TI - [Teaching methodology of research and statistics in nursing schools. I]. PMID- 7886386 TI - [Nursing students and death: a study of the experiences and needs in education]. PMID- 7886387 TI - [Hutu and Tutsi. An impossible coexistence?]. PMID- 7886388 TI - [Responsibility, mainly of the Ruandans]. PMID- 7886389 TI - [Towards a new medical practice. Experiences in Great Britain]. PMID- 7886390 TI - [Discrimination on an ethical basis. The main victim: the child]. PMID- 7886391 TI - Effect of loperamide on lower oesophageal sphincter pressure in idiopathic achalasia. AB - BACKGROUND: We have recently shown that in achalasia patients morphine has a striking inhibitory action on resting lower oesophageal sphincter (LOS) pressure, which is mediated by opioid receptors. The aim of this study was to investigate the effect of a peripheral opioid agonist, loperamide, administered at a dose of 16 mg, on resting LOS pressure in nine patients with untreated idiopathic achalasia. METHODS: All patients underwent two experiments after oral administration of placebo and loperamide, respectively, on separate days and in randomized order. At the end of the placebo experiment we also tested the effect of loperamide as compared with distilled water, both infused intraluminally at the level of the LOS. In the loperamide experiment, after a 60-min basal period, naloxone, 40 micrograms/kg, was injected intravenously, and recordings continued for a further 10 min. RESULTS: Loperamide administered orally decreased (p < 0.01) LOS pressure by 10 +/- 2 mmHg (37 +/- 7%) compared with placebo, and naloxone intravenously failed to block the effect. LOS pressure was not affected by infusion of either distilled water or loperamide at the level of the LOS. CONCLUSIONS: Our findings indicate that in patients with idiopathic achalasia oral administration of loperamide at a high dose markedly decreases resting LOS pressure. This may not occur through opioid receptor stimulation and requires intestinal absorption of the drug. The possible effect of combining a small dose of loperamide with the traditional achalasia drugs awaits further evaluation. PMID- 7886392 TI - Helicobacter heilmannii (formerly Gastrospirillum hominis) gastritis: an infection transmitted by animals? AB - BACKGROUND: The source of infection with Helicobacter heilmannii (formerly Gastrospirillum hominis), a relatively rare causative agent of gastritis in humans, is not clear. It has long been known that this organism occurs in the stomach of domestic animals and pets. METHODS: By performing an epidemiologic investigation on possible contact of patients with Helicobacter heilmannii gastritis with such animals, we made an attempt to gain further information about the source of infection. RESULTS: Of 125 patients with confirmed H. heilmannii infection, 111 provided us with information about contact with animals. Some 70.3% of the patients had contact with one or more animals (as compared with 37% in the 'normal' population); 73% were males, and 1.6% had concomitant infection with H. pylori. CONCLUSIONS: Our analysis indicates that H. heilmannii gastritis is due to its transmission to humans by domestic animals or pets. Concomitant infections by H. heilmannii and H. pylori are very rare, and it is possible that H. heilmannii might protect from infection with H. pylori. However, the results of our retrospective analysis will have to be tested against those of a prospective study investigating the day-to-day situation of the individual patients in greater detail and also be compared with patients not infected with H. heilmannii. PMID- 7886393 TI - Effects of omeprazole and lansoprazole on 24-hour intragastric pH in Helicobacter pylori-positive volunteers. AB - BACKGROUND: The comparative effects of omeprazole and lansoprazole on gastric acidity in Helicobacter pylori-positive subjects and the clearance of H. pylori are unknown. METHODS: Eighteen asymptomatic H. pylori-positive subjects were studied. Each volunteer received 7 days of omeprazole, lansoprazole, or placebo in a randomized, double-blind, crossover study, with a washout period of 4-6 weeks between treatments. At the end of each treatment period 24-h dual-point intragastric pH-metry was performed, and H. pylori clearance was assessed. RESULTS: Both omeprazole (corpus/antrum pH: 5.5/5.5) and lansoprazole (5.4/5.4) increased intragastric pH compared with placebo (1.5/1.3). Over the 24-h recording there was no difference between the two treatments with regard to control of intragastric pH or clearance of H. pylori. CONCLUSION: Omeprazole, 20 mg once daily, and lansoprazole, 30 mg once daily, are comparably effective antisecretory agents in H. pylori-positive subjects. Both agents provide only transient clearance of H. pylori in a few subjects. PMID- 7886394 TI - Omeprazole plus amoxicillin for cure of Helicobacter pylori infection. Factors influencing the treatment success. AB - BACKGROUND: Omeprazole plus amoxicillin may cure Helicobacter pylori infection. However, the published results vary rather widely, and the factors influencing the treatment success remain unclear. METHODS: Four hundred and twenty-three H. pylori-positive patients were treated with 1- or 2-week regimens comprising 40 mg or 80 mg omeprazole and amoxicillin in 11 prospective protocols. A complete set of data was available for 405 patients (ulcer disease, n = 383; dyspepsia, n = 22) and was submitted to uni- and multi-variate statistical analyses to elucidate the factors affecting the cure rates of the infection; 18 patients were lost to follow-up. RESULTS: The overall proportion of H. pylori cure was 76%. Insufficient compliance (p < 0.001), a short duration of treatment (p < 0.001), smoking (p = 0.003), and omeprazole pretreatment (p = 0.041) were the significant independent factors predicting treatment failure, whereas advanced age (p = 0.002), high scores of grade and of activity of gastritis (p = 0.035 and p = 0.019, respectively), and gastric ulcer disease (p = 0.058) were independent factors predicting treatment success. CONCLUSIONS: Several patient- and therapy related factors diminish or increase the rate of H. pylori cure obtained by omeprazole/amoxicillin. These should be considered in future studies comparing different treatment regimens for curing H. pylori infection and also when designing treatment regimens applicable for routine clinical practice. PMID- 7886395 TI - Computerized analysis of ambulatory long-term small-bowel manometry. AB - BACKGROUND: Ambulatory long-term manometry is increasingly being used to study small-bowel motility. This study aimed to develop computer-aided data analysis including the elimination of artefacts, identification of individual phasic contractions, and analysis of aboral propagation. METHODS: Data processing included low-pass filtering, base-line adaptation, cross-comparison of channels, and application of threshold values for contraction parameters. Automated analysis was validated by a visual reference standard. RESULTS: Artefacts were related to cardiovascular and respiratory activity, changes in body posture, and contractions of the abdominal wall. Automated recognition of contractions reached a sensitivity of 92% and a positive predictive value of 88% compared with the visual standard. Mean contraction amplitude and duration of computer analysis were 96% and 93%, respectively, of the visually obtained values. Propagation analysis under ambulatory conditions showed good agreement with previous results by stationary recordings. CONCLUSIONS: Computerized analysis provided valid and reproducible data on small-bowel phasic contractile events and propagative activity by digital long-term manometry. PMID- 7886396 TI - Stereospecific effects of intraduodenal tryptophan on pyloric and duodenal motility in humans. AB - BACKGROUND: L-Tryptophan delays gastric emptying in animals to a greater extent than D-tryptophan, but none of the possible motor mechanisms responsible for this stereospecific effect have been evaluated. METHODS: In 11 healthy volunteers antropyloroduodenal pressures were recorded in the fasted state with a sleeve/sidehole manometric assembly during 20-min intraduodenal infusions (2 ml.min-1) of isotonic L- and D-tryptophan (50 mM, pH 5.7) and normal saline (pH 5.5), given in randomized order. RESULTS: Intraduodenal L-tryptophan increased basal pyloric pressure (p < 0.05), whereas D-tryptophan had no effect. In contrast, L- and D-tryptophan both stimulated (p < 0.05) localized phasic pyloric pressure waves, and there was no significant difference in the responses. The number of duodenal pressure waves was greater during infusion of L-tryptophan than during D-tryptophan (p < 0.05). CONCLUSION: We conclude that intraduodenal tryptophan has stereospecific effects on pyloric and duodenal motility. Although the precise contribution of these differential effects to gastric emptying remains to be clarified, they may be partially responsible for the differences in gastric emptying of D-tryptophan and L-tryptophan. PMID- 7886397 TI - Effects of hyperglycemia on interdigestive gastrointestinal motility in humans. AB - BACKGROUND: Gastrointestinal motility disorders are common in patients with diabetes mellitus. Recent studies indicate that hyperglycemia can affect gastric emptying and gastric motility in healthy subjects and diabetics. METHODS: The effect of acute hyperglycemia on gastrointestinal motility was studied with a manometric technique in healthy subjects. Seven individuals, four men and three women, 23-34 years old, were studied on 2 different days. On 1 of the days a 5-h registration was performed after an overnight fast. On another day and after an initial basal period, acute steady-state hyperglycemia was induced by intravenous glucose infusion for 90 min. Motility variables were evaluated in four segments: in the gastric antrum, the proximal duodenum, the distal duodenum, and the proximal jejunum. RESULTS: Fasting migrating motor complex rhythm including migration of phase III prevailed during hyperglycemia. Compared with euglycemia, the motility index in phase II was lower during hyperglycemia in all segments studied. In the antrum the difference was 62% (p < 0.01); in the proximal duodenum, 37% (p < 0.01); in the distal duodenum, 44% (p < 0.05); and in the jejunum, 58% (p < 0.01). During hyperglycemia the prevalence of propagated contractions in phase II was significantly lower than during euglycemia both in the antrum and the proximal duodenum. In the last part of phase III in proximal duodenum most individual contractions were propagated in orad direction compared with early phase III, and this difference persisted during hyperglycemia. The number of long clusters was significantly increased during hyperglycemia as compared with euglycemia: 2.0 +/- 0.6 per hour versus 0.4 +/- 0.14 (p < 0.01). In late phase II plasma levels of motilin and pancreatic polypeptide were significantly decreased during hyperglycemia. CONCLUSION: Hyperglycemia not only reduces the motility in the stomach but also inhibits motility in both the duodenum and the jejunum. The results show that acute hyperglycemia has an important impact on small-intestinal motility. PMID- 7886398 TI - The effect of cisapride and metoclopramide on human digestive and interdigestive antroduodenal motility. AB - BACKGROUND: To date, there is little information available about the effect of cisapride and metoclopramide on gastroduodenal pressure waves and their space/time orientation. METHODS: Antroduodenal pressures (two antral, three duodenal recording sites) were measured in nine healthy volunteers. Cisapride (10 mg), metoclopramide (10 mg), and placebo were administered intravenously on different days in a randomized manner. RESULTS: During the interdigestive state cisapride increased the motility index significantly in the antrum (p < 0.05) and duodenum (p < 0.005), metoclopramide only in the duodenum (p < 0.01). Antroduodenal coordination was significantly (p < 0.01) improved by cisapride but not by metoclopramide. There is evidence of antroduodenal coordination even during the interdigestive state. After a liquid test meal an increase in the antroduodenal motility index (p < 0.05), in the rate of prograde antroduodenal peristalsis (p < 0.01), and in antroduodenal coordination (p < 0.01) was caused by cisapride but not metoclopramide. Both prokinetics decreased (p < 0.01) retrograde antroduodenal peristalsis. CONCLUSION: Cisapride significantly improves antroduodenal coordination and antroduodenal motility; metoclopramide seems to be less effective. PMID- 7886399 TI - A retrospective assessment of the clinical value of jejunal disaccharidase analysis. AB - BACKGROUND: The measurement of jejunal disaccharidases is used by several gastroenterologists when investigating suspected small-bowel disease. The clinical value of this analysis is assessed. METHOD: The histology and disaccharidase results in 1585 jejunal biopsy specimens were reviewed retrospectively. RESULTS: Disaccharidase and histology results concurred in most cases (72%). However, disaccharidases were an insensitive indicator of small bowel disease: low levels were found in only 65% of coeliac patients with villous atrophy, 15% of patients with giardiasis, and 6% of patients with villous atrophy associated with non-coeliac histology. Low disaccharidase levels were sometimes found in patients with normal histology (1.6%) and when biopsy specimens were unwittingly taken from non-jejunal sites (1.4%). Isolated low lactase activities were found in 3.2%. Usually this finding was not clinically relevant because patients had no symptoms of lactose intolerance (38%), had another diagnosis that responded to appropriate treatment (8%), or had no response to a low-lactose diet (14%). In 16 patients sucrase activities were markedly low, and this investigation proved central to the diagnosis of sucrase-alpha-dextrinase deficiency, which was subsequently confirmed in 9. CONCLUSION: Jejunal disaccharidases are clinically useful only in the diagnosis of sucrase-alpha dextrinase deficiency. We recommend that their measurement be reserved for the investigation of patients suspected of having this condition. PMID- 7886401 TI - Long-term follow-up in Crohn's disease. Mortality, morbidity, and functional status. AB - BACKGROUND: The purpose of this study was to analyse long-term results of an active approach to surgical treatment of Crohn's disease. METHODS: One hundred and thirty-six patients were studied after first resection for primary Crohn's disease during 1968-77. RESULTS: Mean follow-up was 16.6 years; 18 patients had died (3 of Crohn's disease). Cumulative risk for a second resection was 0.40 (95% confidence interval, 0.29-0.51) at 10 years and 0.45 (0.32-0.58) at 15 years, similar in classical disease and colitis. Cumulative risk of a third and fourth resection was 0.5 at 10 years. Median resected bowel length at the first operation was 8%. After two and three resections the cumulative resection was 23% and 33%, respectively. Of the patients 73% claimed full working capacity and 7% had disability pension. CONCLUSIONS: An active surgical approach in Crohn's disease is associated with low operative mortality and morbidity and good functional results and offers good symptomatic relief. PMID- 7886400 TI - Phospholipids prevent enteric bacterial translocation in the early stage of experimental acute liver failure in the rat. AB - BACKGROUND: Bacterial infections and bacteremia in acute liver failure may at least partly be attributed to translocation of enteric bacteria. Attempts to prevent or treat such infections by the use of antibiotics may instead result in overgrowth of surviving microbes. METHODS: In the present study, normal saline (1.5 ml/100 g body weight), phosphatidylcholine (1.5 ml/100 g body weight), and phosphatidylinositol (1.5 ml/100 g body weight) were orally administered by means of a gastric tube both 12 h and 30 min before operation. Effects of enteric administration of phospholipids on the prevention of enteric bacterial translocation, intestinal and mucosal mass, and enterocyte protein contents in acute liver failure induced by subtotal liver resection in the rat were evaluated. RESULTS: The incidence of bacterial translocation increased significantly 2 and 4 h after 90% hepatectomy as compared with sham-operated animals. Enteric administration of phospholipids, however, significantly reduced the incidence of bacterial translocation after 90% hepatectomy. Phospholipid treatment prevented the postoperative decrease in intestinal mucosal mass and enterocyte protein content. CONCLUSIONS: Enteral administration of phospholipids thus seems to protect against translocation of enteric bacteria and prevent against a decrease in intestinal mucosal mass and enterocyte protein content after subtotal hepatectomy in the rat. PMID- 7886402 TI - Evaluation of pepsinogen A and gastrin-17 as markers of gastric cancer and high risk pathologic conditions. AB - BACKGROUND: Gastric cancer remains a major cause of mortality and will remain so for the lifetime of current clinicians. Many cancers are diagnosed at a stage when current therapy cannot provide the hope of cure. A method for early detection of gastric cancer which can be widely applied is needed. The serum levels of pepsinogen A and gastrin-17 have been shown to vary in the presence of pathologic conditions of the gastric mucosa and may provide such a tool. METHODS: Serum samples were obtained from 432 patients undergoing endoscopy for undiagnosed dyspepsia. The levels of pepsinogen I and gastrin-17 were estimated by radioimmunoassay and compared with the final diagnosis. Discriminant analysis was performed to assess the value of the peptides predicting the presence of gastric cancer and the high-risk mucosal changes. RESULTS: Abnormal levels of gastrin-17 or pepsinogen A were found in 60% of patients with gastric cancer and 60% of those with one of the high-risk mucosal changes, the latter figure rising to 75% when the changes were in the upper third of the stomach. Discriminant analysis showed the log of gastrin-17 and log of pepsinogen A to be the best predictors of the high-risk mucosal changes, gastric cancer, and benign disease. CONCLUSIONS: These results confirm gastrin-17 and pepsinogen A as markers of pathologic gastric conditions and suggest that these peptides are potential screening tools worthy of further assessment. PMID- 7886403 TI - Concanavalin-A-extractable non-mucous glycoprotein concentrations in gallbladder bile of cholesterol gallstone patients. AB - BACKGROUND: The relationship between protein concentrations and the nucleation activity of bile in cholesterol gallstone patients has already been investigated. Nucleation promoters are mucins and concanavalin A (Con-A)-extractable glycoproteins. Nucleation inhibitors are apolipoproteins. We wanted to investigate whether a change in concentration of apolipoprotein A-I (Apo A-I) or Con-A in the bile of cholesterol stone carriers is dependent on the nucleation time. METHODS: Total protein was measured by fluorescence photometry, and Con-A extractable glycoproteins were separated by their affinity to lectins and measured by photometry. Apolipoproteins were measured by radioactive competitive protein binding assay. RESULTS: The protein concentrations in our bile samples were 2.41 +/- 1.08 mg/ml for the whole group, 2.73 +/- 1.07 mg/ml for a nucleation time less than 3 days, and 2.04 +/- 1.00 for a longer nucleation time. The concentration of the Con-A fraction accounted for 0.289 +/- 0.096 mg/ml, 0.306 +/- 0.081 mg/ml, and 0.274 +/- 0.109, respectively. The Apo A-I concentration was 52 +/- 64 micrograms/ml; 50 +/- 56 micrograms/ml for a nucleation time less than 3 days and 85 +/- 133 micrograms/ml for a longer nucleation time. CONCLUSIONS: Obviously, individual protein fractions have an effect on the nucleation behaviour of gallbladder bile in cholesterol gallstone patients. PMID- 7886404 TI - Endoscopic ultrasonographic evaluation of gastric ulcer healing on treatment with proton pump inhibitors versus H2-receptor antagonists. AB - BACKGROUND: It has been reported that time to peptic ulcer healing is shorter with proton pump inhibitors (PPI) than with H2-receptor antagonists (H2-RA). This study was designed to examine the difference in the healing process between gastric ulcers treated with PPI and those treated with H2-RA. METHODS: The healing of deep gastric ulcers treated with PPI (n = 11) or H2-RA (n = 13) was evaluated with endoscopic ultrasonography (EUS). Every 2 weeks during treatment EUS variables such as the width and the depth of the ulcer crater, the thickness and size of the low echoic area of the ulcer base, and the distance of the disrupted muscularis propria were measured. The contraction rates of EUS variables, the ratios of the contraction rate of the depth to that of the width of the ulcer crater (D/W ratio) and the contraction rate of the distance of the disrupted muscularis propria layer to that of the width of the ulcer crater (Dm/W ratio) were calculated. RESULTS: Only at week 2 were the D/W ratio and Dm/W ratio significantly higher in the group receiving PPI (D/W ratio, 1.79 +/- 0.701; Dm/W ratio, 0.938 +/- 0.207) than in the group receiving H2-RA (D/W ratio, 1.10 +/- 0.559; Dm/W ratio, 0.641 +/- 0.166). CONCLUSION: This study demonstrated that PPI therapy is associated with more rapid and stronger healing than obtained with H2 RA during the early treatment period. PMID- 7886405 TI - The diagnostic value of repetitive preoperative analyses of C-reactive protein and total leucocyte count in patients with suspected acute appendicitis. AB - BACKGROUND: Studies have shown that C-reactive protein (CRP) and total leucocyte count (WBC) in suspected acute appendicitis analysed only on admission gave valuable information to guide the surgeon. The aim of this study was to investigate the usefulness of CRP and WBC measured repetitively before operation. METHODS: During a 1-year period 227 patients were studied before emergency appendicectomy. CRP and WBC were analysed every 4th h. The upper limits of the reference intervals used were 9.0 x 10(9)/l for WBC and 10 mg/l for CRP. RESULTS: Of the 227 appendicectomized patients, 170 (75%) had acute appendicitis. Sixty six of the patients were tested on two or more occasions every 4th h. Forty-six of these patients had appendicitis; repetitive tests showed a continuing rise in CRP values but a continuing decrease in WBC. The negative appendicectomy rate among these 66 patients was 30%, which theoretically would have fallen to 19% if patients with normal results had not been subjected to surgery. CONCLUSIONS: Repeated laboratory tests for CRP and WBC should be performed in patients with suspected acute appendicitis requested to stay for further observation. If these test results are normal, the surgeon should preferably refrain from operating but consider other differential diagnoses. PMID- 7886406 TI - Convalescence after inguinal herniorrhaphy. AB - BACKGROUND: The aim of this investigation was to evaluate factors influencing the length of convalescence after ambulant inguinal hernia repair. METHODS: One hundred and twenty-three patients were followed up to assess when they returned to work, considered that they had regained full working capacity, and resumed leisure time activities. The length of sick leave was recommended on the basis of the load of the occupation. RESULTS: Half of the patients had a longer sick leave than recommended by the surgeon. Active and heavy work showed an independent significant positive correlation to the length of sick leave. Median sick leave among these patients was 42 days, which was the time they considered that they had regained full working capacity and 1 week after they had resumed their leisure time activities. Median sick leave among patients with sedentary or moderately active work was 9 days before regaining full working capacity and 12 days before resuming leisure time activities. CONCLUSIONS: Other factors than load of work and surgeon's advice seem to play a role in the patient's decision about when to resume normal activities on the job. PMID- 7886407 TI - Acute tolerance to furosemide. Pretreatment with captopril or prazosin does not influence diuresis and natriuresis. AB - To investigate whether the development of acute tolerance to furosemide in human subjects could be prevented or delayed by angiotensin converting enzyme inhibition or alpha 1-receptor blockade, a study was conducted on healthy volunteers. The protocol on the experimental days was identical except for pre treatment with placebo, captopril or prazosin. During continuous furosemide infusion with urinary furosemide excretion at a constant rate, the subjects became progressively dehydrated, with a maximal decrease in plasma volume of 9 11%. The diuretic/natriuretic response to furosemide was similar in the three protocols. Acute tolerance to diuresis developed earlier than that to natriuresis, again with no differences between the protocols. Not until the plasma volume had decreased by 9% did the natriuresis diminish significantly. In the placebo and captopril protocols acute tolerance was caused mainly by a decreased glomerular filtration rate, and in the prazosin protocol mainly by increased tubular reabsorption. It is concluded that neither ACE inhibition nor alpha 1-receptor blockade prevented or delayed the acute tolerance to furosemide. The results suggest that acute tolerance to furosemide can be induced through different but complementary homeostatic mechanisms in the kidney. PMID- 7886408 TI - Long-term outcome after renovascular surgery. Comparison between thoracoretroperitoneal/saphenous vein and transabdominal/Dacron prosthesis bypass grafting. AB - The outcomes of 16 patients operated on for renovascular hypertension (RH) are analyzed. Eight had undergone surgery by the thoracoretroperitoneal approach with saphenous vein bypass grafting, and 8 by the transabdominal approach with a Dacron prosthesis. Distinct differences in favour of the former group were found after an average of 6 years of follow-up. PMID- 7886409 TI - Nocturnal enuresis: change of nocturnal voiding pattern during alarm treatment. AB - In a prospective clinical study of the outcome of alarm treatment in nocturnal enuretics, 60 children were included: 40 boys and 20 girls, mean age 8.2 years (range 5.1-14.4). All were treated with enuresis alarms and had 2 or more enuretic events during the initial 14 days of treatment. None had diurnal enuresis. In each child, the enuretic and voluntary voiding frequencies during the initial 14 and last 14 days of treatment were compared. We found that 43 children had a 75% reduction or more of the enuretic events. 28 children substituted the former enuretic events by sleep, 15 changed the enuresis by voluntary voidings. Only 17 children had no effect of the alarm treatment. No parameters were found to predict the outcome. In conclusion, the outcome of successful alarm treatment occurs in two distinct forms. Either the child is left asleep without wetting his bed; or the child wakes up spontaneously from sleep and goes to the bathroom. PMID- 7886410 TI - Functional bladder capacity and calcium-creatinine quota in enuretic patients, former enuretic and non enuretic controls. AB - Functional bladder capacity and Urine Calcium/creatinine quota were investigated in 13 patients with primary nocturnal enuresis, 15 former enuretic patients and 15 controls. The functional bladder capacity was measured in ml and determined by a standardised daytime oral water load test which was performed in the homes. There was an age-related increase in bladder capacity in all three groups. There was no significant difference between any of the groups in bladder capacity. There wasn't any elevation of the calcium/creatinine quota in the enuretic patients, but former enuretic children had an increased calcium creatinine quota in the morning urine. Calcium/creatinine quota was also studied in 15 adult former enuretics and 15 adult control individuals without finding any difference between the groups. This investigation suggests that the functional bladder capacity is not a major pathogenic factor in primary nocturnal enuresis. PMID- 7886411 TI - Absorption characteristics of lignocaine following intravesical instillation. AB - The systemic absorption of topical lignocaine applied intravesically was studied in 11 patients with indwelling catheters. Group A patients (n = 9) had lignocaine 400 mg (as 40 ml of a 1% solution) instilled into the bladder for 1 hour whilst in Group B patients (n = 2) the application was for 2 hours. The mean maximum lignocaine concentration measured in Group A patients was 121 ng ml-1 with a time to maximum concentration of 60-90 minutes. The two patients in Group B had corresponding values of 410 and 1580 ng ml-1 respectively at 120 minutes. Transitional cell epithelium, like intact skin, constitutes a significant barrier to the uptake of topically applied lignocaine which, from the bladder, is both slow and limited. Intravesical application is safe (maximum levels in Group A patients being x 30 less than the minimal toxic level of lignocaine) but its clinical efficacy remains to be determined. PMID- 7886413 TI - Oestrogen receptor investigations in bladder tumours. AB - Transitional cell tumours of the bladder in 12 men and 12 women were investigated for oestrogen receptors. All tumours and surrounding urothelium were found to be receptor-negative. PMID- 7886412 TI - Bacillus Calmette-Guerin therapy for high-risk superficial bladder cancer. AB - Twelve consecutive patients with carcinoma in situ (CIS) and 17 with T1G3 transitional cell cancer of the bladder were given intravesical Bacillus Calmette Guerin (BCG) therapy after transurethral resection of all visible lesions. BCG (150 mg in 50 ml normal saline) was given once weekly for 12 weeks and then once monthly for 6 months. The median follow-up was 2.5 years in the CIS group and 3 years in the T1G3 group, with cystoscopy, cytology and random biopsies performed every 3 months. Two of the 12 CIS tumours relapsed, with stage progression (T2G3). Of the 17 T1G3 transitional cell cancers, two relapsed with Ta-1, G1-2 and four progressed to T2-3G3 requiring cystectomy (3) or irradiation (1). One of these four patients died of metastatic disease. BCG therapy thus was effective in preventing progression CIS, but less useful for such purpose in T1G3 transitional cell tumours, for which it cannot be recommended as standard treatment. PMID- 7886414 TI - Blood coagulation status after transurethral resection of the prostate. AB - We examined for a possible correlation between coagulopathy and fluid absorption, serum level of prostatic acid phosphatase (S-PAP) and blood loss in 25 patients undergoing transurethral resections of the prostate (TURP). Blood coagulation parameters were measured before and at the end of TURP and 10 and 24 hours later. Fluid absorption was measured by the ethanol method. There was a close correlation between the changes in haemostatic parameters and blood haemoglobin concentration. No relationship was found between the coagulation status and fluid absorption, S-PAP or blood loss during the operation. Fibrinolysis was evidenced by increasing titres of fibrin degradation products in most patients. However, no increase occurred in the two patients who required reoperation because of severe postoperative bleeding, which implies that fewer blood clots were formed in these cases. We conclude that the coagulation parameters during and after TURP varies primarily with the dilution of the blood. PMID- 7886415 TI - Transurethral catheter removal after bilateral orchiectomy for prostatic carcinoma associated with acute urinary retention. AB - In the period 1986-1990 a total of 69 patients with advanced prostate cancer and urinary retention underwent orchiectomy followed by removal of the indwelling catheter during the 3 month/postoperative period. The mean follow-up time was 32 months. Regarding urination after catheter removal the success-rate was 62% (43/69) and 84% of these patients were satisfied with the procedure. For these 43 patients the median time without the catheter was 21.5 months. Eleven patients with success developed a new attack of urinary retention. Bladder catheter removal during 3 months after orchiectomy for patients with advanced prostate cancer and urinary retention is recommended. PMID- 7886416 TI - The skin response in evaluation of the sympathetic chains after retroperitoneal lymphadenectomy. Preliminary report. AB - The sympathetic skin response (SSR) permits recording of the sympathetic amyelinic fibres activity in relation to the function of sudoriparous glands. We recorded the SSR to check the efficacy of "nerve-sparing" technique in surgery of the sympathetic retroperitoneal postganglionic fibres following lymphadenectomy in nonseminomatous testis cancer. The results showed that SSR can be used to verify the integrity of the lumbar sympathetic chains after retroperitoneal lymphadenectomy. PMID- 7886417 TI - Intraurethrally infused capsaicin induces penile erection in humans. AB - Capsaicin-sensitive primary afferents widely innervate the genitourinary tract and play an important role in the integration of various mechanisms which activate reflexes leading to penile erection. We investigated the effect of intraurethral capsaicin infusion in psychogenically impotent men. The 20 patients were prospectively randomized to four groups, each of five men. Group A received intraurethral infusion of saline solution, group B intraurethral capsaicin (10( 5) M), group C intracavernosal papaverine hydrochloride (8 mg) plus intraurethral saline infusion, and group D intracavernosal papaverine hydrochloride (8 mg) plus intraurethral capsaicin (10(-5) M). The penile response was recorded real-time. Intraurethral capsaicin induced penile erection, as did the papaverine injection, while saline infusion was without effect. The erectile response to intraurethral infusion of capsaicin is suggested to involve activation of a urethra-corpora cavernosa reflex arc. Further studies are necessary to clarify if this arc is integrated at central nervous system level or is locally triggered, and if it may have pathophysiologic implications. PMID- 7886418 TI - Renal thoracic ectopia. A case report. AB - We report a case that presented with an opacity on chest X-ray that was found to be an abnormal ectopic kidney. Renal ectopia is rare and usually does not require treatment. PMID- 7886419 TI - Spontaneous kidney rupture due to a metastatic renal tumour. Case report. AB - Spontaneous rupture of the kidney is an uncommon entity. In most cases the non traumatic rupture is associated with underlying diseases of the kidney, the most frequent being renal tumours. We report the case of a spontaneous kidney rupture due to a renal metastasis from an adenocarcinoma of the colon. PMID- 7886420 TI - Pulmonary tumour and inferior vena cava tumour thrombus: rare presentation of renal transitional cell carcinoma. Case report. AB - A transitional cell carcinoma from the pyelocaliceal system, initially presenting as a pulmonary tumour, extended into the inferior vena cava, the tenth reported case of this type. The literature is reviewed with special reference to vena cava involvement by such tumours and immunohistochemical staining pattern. PMID- 7886421 TI - Mixed prostatic carcinoma containing malignant squamous element. Reports of two cases. AB - Two cases of mixed prostatic carcinoma are reported. A 67-year-old man with mixed urothelial and squamous cell carcinoma died 10 months after diagnosis despite hormonal therapy and pelvic irradiation. A 70-year-old man with adenosquamous carcinoma responded well to such treatment. PMID- 7886422 TI - Malignant fibrous histiocytoma of the prostate. Case report. AB - A prostatic tumour removed suprapubically in a 57-year old man was found to be a malignant fibrous histiocytoma. Postoperative radiation therapy was given and 3 1/2 years later chemotherapy, epirubicin was initiated due to a local recurrence and lung metastases. Now 6 years later the health condition is good, lung metastases have not proceeded. Adjuvant radiation and chemotherapy after surgery may have a favourable effect on the outcome of MFH of the prostate. PMID- 7886423 TI - Bilateral Leydig cell tumors with unilateral cryptorchidism. Case report. AB - Bilateral leydig cell tumors of testes are very rare. There is no evidence from literature that in the cryptorchid man, bilateral leydig cell tumors are prone to develop. We report a man with bilateral leydig cell tumors in association with unilateral cryptorchidism. PMID- 7886424 TI - Urethral hemangioma managed with sclerotherapy. Case report. AB - A 15-year-old boy presented with bleeding per urethram due to extensive urethral hemangioma. Endoscopic sclerotherapy resulted in control of bleeding, resolution of the hemangioma and no stricture formation. PMID- 7886425 TI - Evaluation of and methods to change muscle tone. PMID- 7886426 TI - Dynamic changes in muscle structure and electrophysiology in late polio with aspects on muscular trainability. PMID- 7886427 TI - Mechanical evaluation of muscle power in clinical practice with some aspects on training. AB - Effects of training treatment and rehabilitation during sickness/trauma involving the muscles are important factors to quantify. This involves an increasing need for muscle tests. PMID- 7886428 TI - Motor control in chronic spinal cord injury patients. PMID- 7886429 TI - Functional electrical stimulation. PMID- 7886430 TI - Adaptation of skeletal muscle to increased neuromuscular activity as induced by chronic low frequency stimulation. PMID- 7886431 TI - Can gait analysis improve gait training in stroke patients. PMID- 7886432 TI - Possibilities to evaluate and diminish the effects of the trauma in spinal cord lesions. An experimental study in the rat. PMID- 7886433 TI - Rising and sitting down in stroke patients. Auditory feedback and dynamic strength training to enhance symmetrical body weight distribution. AB - The purpose was to study vertical ground reaction force feedback and dynamic knee extensor training used to enhance stroke patients' symmetrical body weight distribution while rising and sitting down. Sixteen healthy subjects and 51 stroke patients participated in the studies. Two vertical strain gauge force transducers attached to two force-measuring platforms were used to measure body weight distribution over the lower limbs. An auditory feedback device, specially developed for training body weight distribution on the paretic leg, employed two electronic balances sensing vertical forces from each foot, separately. Torque of maximal voluntary eccentric and concentric knee extensor and flexor actions at 30, 60, 120, 180 and 240 deg/s was recorded with an isokinetic dynamometer together with surface electrodes from the quadriceps and hamstring muscles. When instructed to rise with even body weight on each lower limb, the stroke patients loaded the paretic leg more than when rising habitually, indicating that stroke patients have a latent motor capacity. Stroke patients' own estimations on visual analogue scales of body weight distributed on the paretic leg correlated with measured loading of the paretic leg in rising. After six weeks of training with auditory feedback of vertical ground reaction forces in the acute phase after stroke, the patients improved their loading of the paretic leg compared to a control group. The patients distributed body weight over the lower limbs nearly symmetrically while rising and while sitting down. The peak torque was not greater, however, than in the control group, rising with an asymmetrical body weight distribution. This implies that the patients after feedback training were better at using the knee extensor torque of the paretic leg to attain symmetrical body weight distribution over the lower extremities. Changes in improvement of physical performance and sitting to standing were greater than in the control group. No differences between groups were seen in performance of activities of daily living. Body weight distribution over the limbs in rising and in sitting down was re-tested on average 33 months after end of training. The symmetrical weight distribution after feedback training was not maintained over time. Knee extensor strength improved after six weeks of eccentric and concentric training, starting on average 27 months after stroke. The increase in strength was related to enhanced activation of agonist EMG activity. Eccentric training seems to be superior to concentric training with reference to a) improved body weight distribution over the lower limbs in rising, to b) increased knee extension torque and to c) increased agonist EMG activity without a concomitant, augmented EMG activity of the antagonistic knee flexor muscles. It was concluded that stroke patients have a latent motor capacity, that six weeks auditory feedback training promotes symmetrical body weight distribution which, however, is not consistent over time and that isokinetic eccentric training is superior to concentric training with reference to weight distribution in rising, knee extension torque and EMG activity. PMID- 7886434 TI - The crystal ball and the trumpet call. PMID- 7886435 TI - Malaria vaccine. PMID- 7886436 TI - Detecting Alzheimer's disease. PMID- 7886437 TI - Detecting Alzheimer's disease. PMID- 7886438 TI - Detecting Alzheimer's disease. PMID- 7886439 TI - U.S. supercomputing ... weighs future of computer centers. PMID- 7886440 TI - Japanese panel OKs IVF screening. PMID- 7886442 TI - French biomedicine. A $51 million incentive to cooperate. PMID- 7886441 TI - Varmus orders up a review of the science of gene therapy. PMID- 7886443 TI - Putting game theory to the test. PMID- 7886444 TI - Agriculture. Playing chicken with an epidemic. PMID- 7886445 TI - Getting a grip on G protein function in C. elegans. PMID- 7886446 TI - Through the glass lightly. PMID- 7886447 TI - Navigating the folding routes. PMID- 7886448 TI - The new path to preventing ulcers. PMID- 7886449 TI - Seeing through the dust: martian crustal heterogeneity and links to the SNC meteorites. AB - Through the application of new analytical techniques to high spatial resolution imaging spectrometer data, the ferrous mineralogy of major volcanic terrains on Mars is shown to consist of significant fractions of both low- and high-calcium pyroxene. Changes in the relative abundances of these pyroxenes are observed for units of different age and morphology, even in regions with higher degrees of alteration and contamination from dust. Volcanic rocks with these characteristics are uncommon on Earth but are typical of the basaltic SNC meteorites (shergottites, nakhlites, and chassignites) thought to be from Mars. Thus, it is possible to infer, even through the veil of dust, that the SNC meteorites have mineralogic affinities to major volcanic provinces on Mars and are therefore truly representative of the heterogeneity observed on the surface of the "red planet". PMID- 7886450 TI - Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis. AB - Resistance to isoniazid in Mycobacterium tuberculosis can be mediated by substitution of alanine for serine 94 in the InhA protein, the drug's primary target. InhA was shown to catalyze the beta-nicotinamide adenine dinucleotide (NADH)-specific reduction of 2-trans-enoyl-acyl carrier protein, an essential step in fatty acid elongation. Kinetic analyses suggested that isoniazid resistance is due to a decreased affinity of the mutant protein for NADH. The three-dimensional structures of wild-type and mutant InhA, refined to 2.2 and 2.7 angstroms, respectively, revealed that drug resistance is directly related to a perturbation in the hydrogen-bonding network that stabilizes NADH binding. PMID- 7886451 TI - Evidence from 18S ribosomal DNA that the lophophorates are protostome animals. AB - The suspension-feeding metazoan subkingdom Lophophorata exhibits characteristics of both deuterostomes and protostomes. Because the morphology and embryology of lophophorates are phylogenetically ambiguous, their origin is a major unsolved problem of metazoan phylogenetics. The complete 18S ribosomal DNA sequences of all three lophophorate phyla were obtained and analyzed to clarify the phylogenetic relationships of this subkingdom. Sequence analyses show that lophophorates are protostomes closely related to mollusks and annelids. This conclusion deviates from the commonly held view of deuterostome affinity. PMID- 7886452 TI - Sodefrin: a female-attracting peptide pheromone in newt cloacal glands. AB - A decapeptide called sodefrin was isolated from the abdominal gland of the cloaca of the male red-bellied newt, Cynops pyrrhogaster. The native peptide, as well as the synthetic one, had a female-attracting activity. Sodefrin was found in the apical portion of the epithelial cells of the abdominal gland. Sodefrin is apparently species specific because it did not attract females of Cynops ensicauda. This is the first amphibian pheromone to be identified and the first peptide pheromone identified in a vertebrate. PMID- 7886453 TI - Epithelial antibiotics induced at sites of inflammation. AB - The role of antimicrobial peptides in epithelial defense is not fully understood. An epithelial beta-defensin, lingual antimicrobial peptide (LAP), was isolated from bovine tongue and the corresponding complementary DNA cloned. LAP showed a broad spectrum of antibacterial and antifungal activities. LAP messenger RNA abundance was markedly increased in the epithelium surrounding naturally occurring tongue lesions. This increase coincided with the cellular hallmarks of acute and chronic inflammation in the underlying lamina propria, supporting a role for epithelial antimicrobial peptides as integral components of the inflammatory response. PMID- 7886454 TI - Modulation of serotonin-controlled behaviors by Go in Caenorhabditis elegans. AB - Seven transmembrane receptors and their associated heterotrimeric guanine nucleotide-binding proteins (G proteins) have been proposed to play a key role in modulating the activities of neurons and muscles. The physiological function of the Caenorhabditis elegans G protein Go has been genetically characterized. Mutations in the goa-1 gene, which encodes an alpha subunit of Go (G alpha o), cause behavioral defects similar to those observed in mutants that lack the neurotransmitter serotonin (5-HT), and goa-1 mutants are partially resistant to exogenous 5-HT. Mutant animals that lack G alpha o and transgenic animals that overexpress G alpha o [goa-1(xs) animals] have reciprocal defects in locomotion, feeding, and egg laying behaviors. In normal animals, all of these behaviors are regulated by 5-HT. These results demonstrate that the level of Go activity is a critical determinant of several C. elegans behaviors and suggest that Go mediates many of the behavioral effects of 5-HT. PMID- 7886455 TI - Participation of the protein Go in multiple aspects of behavior in C. elegans. AB - The goa-1 gene encoding the alpha subunit of the heterotrimeric guanosine triphosphate-binding protein (G protein) Go from Caenorhabditis elegans is expressed in most neurons, and in the muscles involved in egg laying and male mating. Reduction-of-function mutations in goa-1 caused a variety of behavioral defects including hyperactive movement, premature egg laying, and male impotence. Expression of the activated Go alpha subunit (G alpha o) in transgenic nematodes resulted in lethargic movement, delayed egg laying, and reduced mating efficiency. Induced expression of activated G alpha o in adults was sufficient to cause these phenotypes, indicating that G alpha o mediates behavior through its role in neuronal function and the functioning of specialized muscles. PMID- 7886456 TI - Development of a mouse model of Helicobacter pylori infection that mimics human disease. AB - The human pathogen Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. The pathogenesis of H. pylori infection in vivo was studied by adapting fresh clinical isolates of bacteria to colonize the stomachs of mice. A gastric pathology resembling human disease was observed in infections with cytotoxin-producing strains but not with noncytotoxic strains. Oral immunization with purified H. pylori antigens protected mice from bacterial infection. This mouse model will allow the development of therapeutic agents and vaccines against H. pylori infection in humans. PMID- 7886457 TI - Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. AB - The neurotrophins are signaling factors important for the differentiation and survival of distinct neuronal populations during development. To test whether the neurotrophins also function in the mature nervous system, the effects of brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophic factor 3 (NT-3) on the strength of synaptic transmission in hippocampal slices were determined. Application of BDNF or NT-3 produced a dramatic and sustained (2 to 3 hours) enhancement of synaptic strength at the Schaffer collateral-CA1 synapses; NGF was without significant effect. The enhancement was blocked by K252a, an inhibitor of receptor tyrosine kinases. BDNF and NT-3 decreased paired pulse facilitation, which is consistent with a possible presynaptic modification. Long-term potentiation could still be elicited in slices previously potentiated by exposure to the neurotrophic factors, which implies that these two forms of plasticity may use at least partially independent cellular mechanisms. PMID- 7886458 TI - Inhibition of ocular dominance column formation by infusion of NT-4/5 or BDNF. AB - During the development of the visual system of higher mammals, axons from the lateral geniculate nucleus (LGN) become segregated into eye-specific patches (the ocular dominance columns) within their target, layer 4 of the primary visual cortex. This occurs as a consequence of activity-dependent synaptic competition between axons representing the two eyes. The possibility that this competition could be mediated through neurotrophin-receptor interactions was tested. Infusion of neurotrophin-4/5 (NT-4/5) or brain-derived neurotrophic factor (BDNF) into cat primary visual cortex inhibited column formation within the immediate vicinity of the infusion site but not elsewhere in the visual cortex. Infusion of nerve growth factor, neurotrophin 3 (NT-3), or vehicle solution did not affect column formation. These observations implicate TrkB, the common receptor for BDNF and NT 4/5, in the segregation of LGN axons into ocular dominance columns in layer 4. Moreover, they suggest that in addition to their better known roles in the prevention of cell death, neurotrophins may also mediate the activity-dependent control of axonal branching during development of the central nervous system. PMID- 7886459 TI - [The traumatized shoulder in computerized and magnetic resonance tomography]. AB - Diagnosis of traumatic changes of the shoulder can be achieved by several invasive and nonivasive radiological procedures allowing visualization of bony and/or soft tissue structures. With reference to 74 shoulder examinations CT, CT arthrography, and MRI were reviewed and their value for further treatment assessed. Since joint effusions occurred in nearly all cases of glenoid and rotator cuff lesions, a cost-effective strategy for diagnosing traumatic changes of the shoulder is presented. PMID- 7886460 TI - [Long-term results of the modified Eden-Hybinette operation for treatment of recurrent shoulder dislocation]. AB - In a retrospective study we evaluated the long-term results of a modified Eden Hybinette procedure in 76 patients. Besides stability, function, and subjective complaints, we documented in particular the degenerative changes of the joint. Subjective findings revealed excellent or good results in 68.5% of cases. In 20% of the patients the results were fair and in 11.5% poor. Some 66% of the patients had not subjective feeling of joint restriction. However, 25% complained of some and 9% of severe joint restriction. The overall recurrence rate was 13.9%. In patients with atraumatic dislocation the recurrence rate was 12%, in patient with voluntary dislocation it was 50%, and in posttraumatic instabilities the recurrence rate was 4.8%. The Rowe score showed 40% excellent and good results. The poor results were among the patients with redislocation, instabilities with subluxation, and secondary degenerative joint disease with concomitant pain and limitations in the range of motion. In patients with voluntary instabilities the poor results were in the group of redislocators, whereas in the posttraumatic group poor results were mainly due to degenerative joint disease. In 80% of the patients with bone block complications, secondary degenerative joint disease developed. Considering the relatively high recurrence rate and the amount of secondary degenerative joint disease after this procedure, we do not recommend this as a routine procedure for shoulder stabilisation. PMID- 7886461 TI - [Functional treatment concept of acute rupture of the Achilles tendon. 2 years results of a prospective randomized study]. AB - Ultrasonography and MRI are highly reliable and reproducible methods of determining the separation of a ruptured Achilles tendon and the degree of tendon repair in the course of healing. While MRI is expensive, it can be restricted to research and special indications. In a randomized trial a operative treatment and a conservative/functional treatment with a newly developed boot were compared in 50 patients (22 of whom underwent operative treatment and 28, conservative treatment). In this trial there were no significant differences either in the functional results or in the course of healing. Functional treatment in both groups allowed shorter periods of rehabilitation, and acceptance of the boot was particularly high in all patients. PMID- 7886462 TI - [An overview of snow-boarding injuries]. AB - Snowboarding is increasing dramatically in popularity in Switzerland as well as other countries. Work aimed at improving the design of the boards and of the boots and bindings has also increased rapidly during recent years. Most injured snowboarders are fit young men and boys who describe themselves as beginners and have had a minimal amount of instruction at an officially approved training centre. Appropriate snowboard training has mostly been quite inadequate, and protective devices (e.g. waterproofed support gloves). The anatomical distribution and the types of injuries sustained in snowboarding differ from those in alpine skiing. The wrist (and forearm) and the ankle are the most frequent locations of injuries (23%) as against the knee and thumb in alpine skiing. Sprains and strains were the most frequent types of injuries (46%), followed by fractures (28%) and contusions (13.5%). The snowboard injury rate was higher than in alpine skiing (1.7-8/1000 snowboard days versus 2-4/1000 ski days). Falling forward on the slope was the major mechanism of injury (80%), and torsion the next most frequent (20%). Snowboarding injuries were sustained most often on ice and hardpacked snow, compared with soft powder snow for alpine skiing injuries. Appropriate preseason conditioning, snowboarding lessons from a certified instructor, appropriate selection of rigorously tested equipment and use of protective devices are the main steps that must be taken to prevent injuries. PMID- 7886463 TI - [Continuous skin expansion for covering soft tissue defects of the foot sole]. AB - Reconstruction of the weight-bearing area of the sole of the foot is a major surgical problem, regardless of the aetiology of the soft-tissue defects. Numerous reconstruction methods have been described for coverage of plantar defects of the heel with local and free flaps. Skin expansion and skin traction have been described by several authors. According to the Ilizarov technique, a new method has been devised for the closure of posttraumatic soft-tissue defects in the weight-bearing area of the sole by skin stretching with Kirschner wires without the aid of either local or free flaps. The operative procedure is very simple: the sharp ends of Kirschner wires are bent with pliers into hook-shaped semicircles. These ends are then inserted into the skin of the sole at intervals of 3-4 mm, alternately close to and distant from the wound edge. The opposite ends of the K-wires are sandwiched between two small AO plates. These plates are pressed together with screws and nuts; additionally, the ends of the K-wires are bent around the plates to prevent loosening. A frame is set up around the heel and connected to the tibial external fixator. The two plates with the K-wires clamped between are mounted on the threaded rods of an Ilizarov external fixation system. Then the foot is temporarily fixed to the tibia in neutral position by a Schanz screw inserted into the first metatarsal. The soft-tissue defect is treated with moist compresses changed daily.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886464 TI - Surgery on extremities with reflex sympathetic dystrophy. AB - Surgery on extremities suffering from reflex sympathetic dystrophy (RSD) is generally avoided because it is presumed that RSD will recur or worsen. In order to study this problem we analyzed our patients. The affected limb of 47 patients suffering from RSD was operated on for various reasons. If possible, the operation was postponed until the signs and symptoms of RSD decreased at rest and perfusion of the affected limb was optimized; tourniquet haemostasis was avoided, and perioperative intravenous infusion of mannitol was administered. Recurrence of RSD was seen in 6 patients (13%). This recurrence was mild and temporary in 5 patients, but serious and permanent in 1 patient. Surgery on limbs suffering from RSD is not as dangerous as widely believed, but one should be aware of the risk of recurrence of RSD when surgery is being considered. PMID- 7886465 TI - [Heparin-associated thrombocytopenia caused by low-molecular-weight heparin]. AB - Recent studies have shown that low-molecular-weight heparins (LMWH) are not suitable for treating patients with heparin-associated thrombopenia (HAT) type 2, as they can cause the same complications as unfractionated heparin UFH. The case described ist that of concerns as female patient who died after developing HAT type 2 following LMWH given perioperatively to prevent thromboembolism. This case indicates again that LMWH can trigger HAT type 2 even if administered only once a day. For HAT to be successfully treated it is essential that the condition is diagnosed early enough by means of routine regular laboratory checks of the number of thrombocytes during any heparin treatment in order to detect the disease before clinical symptoms become apparent. PMID- 7886466 TI - [Differential therapy of traumatically-induced persistent posterior shoulder dislocation. Review of the literature]. AB - Three-hundred and twenty-nine cases of posterior dislocation of the shoulder documented in 300 articles published in the international literature are reviewed. They included 130 cases in which the duration of the dislocation was longer than 6 weeks and the dislocation could be classified as persistent primary dislocation. This group is the second largest group following that with acute primary dislocation. The mechanism of injury may be direct or indirect force: trauma, convulsions or electrocution are usually responsible for this type of dislocation, which often persists for longer than 6 weeks. Anatomically, 97.5% of dislocations are classified as subacromial. Posterior dislocation of the shoulder is commonly misdiagnosed on plain antero-posterior radiographs, and in over 50% of cases the diagnosis was missed on first examination. The typical signs of primary traumatic posterior dislocation of the shoulder are described. Management of persistent traumatic posterior dislocation of the shoulder depends on the size of the anterior Hill-Sachs lesion, the precipitating mechanism and the duration of dislocation. The results of 109 surgically and 24 conservatively treated dislocations of this type that have been published in the international literature are reviewed. Closed reduction is indicated in carefully selected cases with an anterior Hill-Sachs lesion under 15% of the size of humeral head (measured in the axillary view) that has been dislocation for less than 2 months. In most due to convulsions there was a distinct anterior Hill-Sachs lesion, which led to recurrence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886467 TI - The MR appearance of cruciate ganglion cysts: a report of 16 cases. AB - Intra-articular ganglion cysts arising from the cruciate ligaments are unusual lesions, there being only nine previously reported cases. We report 16 cases and describe their MR appearance. Nine ganglia originated from the posterior cruciate ligament, most often appearing as well-defined multilocular lesions. The seven ganglia arising from the anterior cruciate ligament most often appeared as fusiform cystic lesions extending along and interspersed within the fibers of the ligament. Although uncommon, intra-articular ganglion cysts arising from the knee appear to have a distinctive MR appearance which should allow their correct diagnosis. PMID- 7886469 TI - Musculoskeletal MR imaging: turbo (fast) spin-echo versus conventional spin-echo and gradient-echo imaging at 0.5 tesla. AB - The value of T2-weighted fast spin-echo imaging of the musculoskeletal system was assessed in 22 patients with various neoplastic, inflammatory, and traumatic disorders. Images were acquired with high echo number (i.e., echo train length) fast spin-echo (FSE; TR 2000 ms, effective TE 100 ms, echo number 13, linear k space ordering), conventional spin-echo (SE; TR 2000 ms, TE 100 ms) and gradient echo (GRE) sequences (TR 600 ms, TE 34 ms, flip angle 25 degrees). Signal intensities, signal-to-noise ratios, contrast, contrast-to-noise ratios, lesion conspicuousness, detail perceptibility, and sensitivity towards image artifacts were compared. The high signal intensity of fat on FSE images resulted in a slightly inferior lesion-to-fat contrast on FSE images. However, on the basis of lesion conspicuity, FSE is able to replace time-consuming conventional T2 weighted SE imaging in musculoskeletal MRI. In contrast, GRE images frequently showed superior lesion conspicuity. One minor disadvantage of FSE in our study was the frequent deterioration of image quality by blurring, black band, and rippling artifacts. Some of these artifacts, however, can be prevented using short echo trains and/or short echo spacings. PMID- 7886468 TI - Ossification of the posterior longitudinal ligament: a report of nine cases in non-Oriental patients. AB - Ossification of the posterior longitudinal ligament (OPLL) is a progressive disorder of the spine which may result in spinal cord compression and myelopathy. While prevalent among Japanese, its occurrence in non-Orientals has been infrequently reported. Nine patients with OPLL have been diagnosed and followed at the Emory Clinic Spine Center over a 5-year period. All of the patients had been misdiagnosed before presentation. Five of the nine had undergone a total of eight ineffective operations. Failure to distinguish OPLL from other more common causes of myelopathy can result in delayed or inappropriate treatment. Illustrative cases and radiographic studies are presented. PMID- 7886470 TI - Handigodu disease: a radiological study. A new variety of spondyloepi(meta)physeal dysplasia of the autosomal dominant type. AB - Handigodu disease is a new syndrome of familial spondyloepi(meta)physeal dysplasia. It is inherited as an autosomal dominant trait. The disease is prevalent in a localised area of South India. On the basis of detailed clinical, anthropometric and radiological investigations of 234 affected individuals, it has been observed that different clinical presentations reflect variation in the severity of the disease. All of them could be explained as being caused by defective development of bones as a result of monogenic disorder. PMID- 7886471 TI - Soft tissue hemangiomas: MR manifestations in 23 patients. AB - In order to assess magnetic resonance (MR) findings, MR images of 23 patients with soft tissue hemangiomas were reviewed retrospectively. All but five hemangiomas were proven histologically. All hemangiomas showed high signal intensity on T2-weighted images; common MR findings were high signal intensity in some areas on T1-weighted images (70%), the configuration of multiple small lobules or tubules (57%), and signal voids (70%). We observed all three of these findings in 6 cases (26%), two of three in 11 cases (48%), only one in 5 cases (22%), and none in 1 recurrent case. Five of 11 intramuscular hemangiomas (45%) showed atrophic change of muscles. Parts of the tubular pattern enhanced in 15 out of 17 patients with a T1-weighted sequence after injection of gadopentetate dimeglumine. Dilated vessels were seen in 2 of 4 with MR angiography. No single feature is specific for hemangioma, but a combination of several MR findings may allow a correct diagnosis. PMID- 7886472 TI - Magnetic resonance imaging in acute physeal injuries. AB - Magnetic resonance imaging (MRI) permits noninvasive evaluation of the cartilage of the growth plate and epiphysis. This paper reports three cases where MRI was used to supplement conventional radiography in the assessment of acute physeal injuries. In the first patient, MRI was used for postoperative assessment of a radial neck fracture, avoiding further surgical exploration. In the second case, MRI was compared with ultrasonography in the diagnosis of proximal humeral epiphyseal separation in a neonate. In the third case MRI and computed tomography were compared in evaluation of a Salter-Harris type 4 distal femur fracture. In all cases MRI was diagnostic. MRI is the investigation of choice in acute complex physeal injuries, and is particularly appropriate for use prior to the appearance of the secondary ossification center. PMID- 7886473 TI - O'Donoghue's triad: magnetic resonance imaging evidence. AB - OBJECTIVE: The objective was to search for magnetic resonance imaging evidence of medial collateral ligament (MCL) injury in knees with proven tears of the anterior cruciate ligament (ACL) and medial meniscus; the three abnormalities that make up O'Donoghue's triad. Although the MCL injury can be unapparent clinically, knee joint stability may be compromised. DESIGN: The superficial portion of the MCL was evaluated on 19 MR studies of 16 knees with arthroscopically proven ACL and medial meniscal tears. MCL thicknesses were compared to those on MR images of 19 normal knees. PATIENTS: The injured knees were of 13 men and 3 women, ranging in age from 19 to 56 years; the normal knees were of 10 men and 9 women, ranging in age from 19 to 55 years. RESULTS AND CONCLUSIONS: The medial collateral ligaments of all injured knees were abnormal, and, as a group, they had greater thicknesses and more intraligamentous thickness variability than normal knees. The MR appearance of both ACL and medial meniscal tears served as indirect evidence of MCL injury, with irregular MCL thickening indicative of prior injury. PMID- 7886474 TI - Meniscal ossicle: MR imaging appearance in three patients. AB - Meniscal ossicles are rare. Radiographically, these ossicles often are mistaken for intra-articular bodies. We evaluated the application of magnetic resonance imaging to determine whether this technique is efficacious in differentiating meniscal ossicles from intra-articular bodies. PMID- 7886475 TI - The coracoacromial arch: MR evaluation and correlation with rotator cuff pathology. AB - The relative prevalence of various acromial shapes, appearance of the coracoacromial ligament and enthesophytes along the inferior aspect of the acromioclavicular joint in patients with and without rotator cuff tears were evaluated. Of 76 patients with clinical instability and impingement, 31 had a normal rotator cuff and 45 demonstrated a partial or full tear of the supraspinatus tendon at surgery. Results were compared with those from magnetic resonance (MR) scans of 57 asymptomatic volunteers. Of the 45 patients with a supraspinatus tear, 38% (17) had a flat acromial undersurface (type I), 40% (18) had a concave acromial undersurface (type II), 18% (8) had an anteriorly hooked acromion (type III), and 4% (2) had an inferiorly convex acromion (type IV). Among the 31 patients with a normal rotator cuff at surgery and the 57 asymptomatic volunteers, the respective prevalences of the type I acromion were 39% (12) and 44% (25), of type II 48% (15) and 35% (20), type III 3% (1) and 12% (7), and type IV 10% (3) and 9% (5). Shoulders with surgically proven rotator cuff tears showed a tendential association with a type III acromion (8/45) and statistically significant associations with a thickened coracoacromial ligament (17/45) and acromioclavicular enthesophytes (18/45). For the association between inferiorly directed acromioclavicular joint enthesophytes and rotator cuff tears, age appears to be a confounding factor. The type IV acromion, newly classified by this study, does not have a recognizable association with rotator cuff tears.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886476 TI - Case report 854: Eosinophilic granuloma. PMID- 7886477 TI - Case report 873: Lipoma arborescens (villous lipomatous proliferation of the synovial membrane). AB - A case of lipoma arborescens with typical features was presented. MR imaging established the preoperative diagnosis by visualizing the typical frond-like synovial projections containing fatty tissue. The extent of joint involvement must be fully documented because an open synovectomy is most appropriate in the management of this disease. Although lipoma arborescens is a rare condition, it is important to recognize the MR features due to the large volume of MR examinations of the knee which are performed. PMID- 7886478 TI - Case report 874: Left supraorbital osteoblastoma. PMID- 7886479 TI - Case report 875: Multifocal osteomyelitis--a manifestation of chronic brucellosis. AB - A 62-year-old man who had had chronic brucellosis for at least 14 years, presumably caused by ingestion of unpasteurized milk, presented with recurrent, multifocal osteomyelitis involving both tibias and a humerus, which had a pathologic fracture. Radiographs showed a large destructive lesion in the humeral diaphysis with a pathologic fracture and multiloculated radiolucencies, together with sclerotic zones in multiple long bones. Histologically, necrotizing, granulomatous inflammatory changes were compatible with a diagnosis of osteomyelitis. Bone biopsy cultures and agglutination titers were positive for Brucella abortus. The case represents an uncommon manifestation of Brucella infection which is particularly rare in the United States. A proper clinical examination should lead to consideration of the diagnosis. PMID- 7886480 TI - Case report 876: Aneurysmal bone cyst of the patella. AB - A case of aneurysmal bone cyst of the patella in a 15-year-old woman was presented. An ABC occurring in a female patient is rare, and to our knowledge this is the first report in the literature. All other reports of patellar ABCs reported have occurred in young black men [2, 3]. The radiographic findings and clinical presentation were stressed since they are typical of all benign patellar tumors. Although radiographic findings are usually typical of patellar tumors, CT and MRI may be used for staging and standardization of operative treatment. MRI is also helpful for examining the integrity of the patellar tendon and quadriceps since many of these patients present with malfunction of the extensor mechanism [14]. PMID- 7886481 TI - Case report 877: Giant cell reparative granuloma arising in enchondromatosis. AB - A case of giant cell reparative granuloma in a 16-year-old girl has been reported. This is the first reported case of giant cell reparative granuloma associated with enchondromatosis. In addition to the clinical features, the pathologic findings and differential diagnosis were also discussed. PMID- 7886482 TI - Case report 878: Densely calcifying synovial sarcoma of the hip metastatic to the lungs. AB - We discuss a patient with an occult, densely calcified synovial sarcoma of the hip who came to clinical attention because of pulmonary metastases. When synovial sarcomas present with dense and conglomerate calcification, they may be confused with benign processes such as myositis ossificans or tumoral calcinosis. Malignancies such as extraskeletal osteogenic sarcoma, extraskeletal chondrosarcoma, and mesenchymal chondrosarcoma must also be considered in the differential diagnosis. PMID- 7886484 TI - [The suicidal act. Equipe de l'UMPAJA]. PMID- 7886483 TI - Case report 879: Chondrosarcoma of the spinous process. PMID- 7886485 TI - [The hospital, the caregiver and the suicidal adolescent. Equipe de l'UMPAJA]. PMID- 7886486 TI - [The medical-psychological unit of the Abadie center. Status of the facility. Equipe de l'UMPAJA]. PMID- 7886487 TI - [The medical-psychological unit of the Abadie Center. The therapeutic functions. Equipe de l'UMPAJA]. PMID- 7886488 TI - [Mortality and morbidity of suicide. Epidemiological aspects]. PMID- 7886489 TI - [The helping relationship at the UMPAJA. Equipe de l'UMPAJA]. PMID- 7886490 TI - [The talking group]. PMID- 7886491 TI - [Reception of the families at the UMPAJA]. PMID- 7886492 TI - [From non-rebellion to the mobilization of psychiatric nurses]. PMID- 7886493 TI - [Detection of suicidal intent. Equipe de l'UMPAJA]. PMID- 7886494 TI - [The music studio]. PMID- 7886495 TI - [Drawings]. PMID- 7886497 TI - [Psychosis and psychomotricity]. PMID- 7886498 TI - [The pony workshop]. PMID- 7886496 TI - [The therapeutic story studio]. PMID- 7886499 TI - [An integrated class for psychotic children]. PMID- 7886500 TI - [Care at the day care hospital "La Pomme Bleue"]. PMID- 7886502 TI - [Wednesday's children. Research on a population of psychotic children]. PMID- 7886501 TI - [Working with living spaces. Working on the psychological process of separation]. PMID- 7886503 TI - [Reception, observation and prevention]. PMID- 7886504 TI - [Work in the wading pool. A therapeutic experience with the effect of water on the body]. PMID- 7886505 TI - [A trip to the land of medico-psychological centers. Results of national and regional studies]. PMID- 7886506 TI - [The pitfalls of welcoming]. PMID- 7886507 TI - [Necessary competences and know-how]. PMID- 7886508 TI - [Home visits for evaluation]. PMID- 7886509 TI - [Interinstitutional relations]. PMID- 7886510 TI - [Social suffering in the new quarters]. PMID- 7886511 TI - [When the unusual is foreign. Caring for patients from Southeast Asia]. PMID- 7886512 TI - [Hypnotherapy]. PMID- 7886513 TI - [Prison and the narcotics user]. PMID- 7886515 TI - [Concepts to be defined: mental health, primary, secondary and tertiary prevention and community health]. PMID- 7886514 TI - [Fear of the subway. History of the disease]. PMID- 7886516 TI - [The mandates of adult medico-psychological centers]. PMID- 7886517 TI - Human immunodeficiency virus transmission and surgeons: update. AB - Concerns of patients and health care providers regarding disease transmission in the health care setting are not unique to the current human immunodeficiency virus (HIV) epidemic. The data show that the risk to health care workers (HCWs) from patients is far greater than the risk to patients from HCWs. Despite the high frequency of contact with potentially infected fluids, surgeons appear to have a low occupational risk of acquiring HIV infection. Further, the actual risk of surgeon-to-patient transmission appears to be extremely small. Recommendations that HIV-infected surgeons restrict their practice or inform patients of their HIV status may have little, if any, value. Yet the federal government required states to adopt guidelines on this issue. Since these guidelines vary among the states, HCWs should be familiar with the legal guidelines and penalties in their state. PMID- 7886518 TI - Social security disability: guidelines for medical practitioners. AB - The purpose of this paper is to introduce medical practitioners to the concepts and function of the Social Security Administration's process of awarding disability benefits. Better understanding of this massive and important program will enable physicians to focus on and present appropriate information. This will facilitate processing of applications to the benefit of physicians, patients, and society. PMID- 7886519 TI - Psychiatry and the practice of medicine: the need to integrate psychiatry into comprehensive medical care. AB - Psychiatric problems are common in general medical practice and strongly influence medical utilization. A number of studies have shown the positive effects of psychiatric interventions for both medical inpatients and outpatients. Unfortunately, historic and economic forces have tended to keep the medical and mental health components of care separated. This paper presents information supporting the need to reintegrate psychiatry into medical practice. Such reintegration will require a shift in the location of mental health clinicians into the primary care setting, a change in the curriculum of medical residents, and a clearer definition of the role of psychiatry in relation to the other mental health professions. PMID- 7886520 TI - The impact of rheumatology in the primary care setting: one rheumatologist's odyssey. AB - I report my experience during one 6-month period as the sole rheumatologist running a weekly clinic at a small community hospital. The report illustrates the impact of rheumatologic expertise in an environment well-served by generalists and other medical subspecialists. This experience identifies important gaps in the education of generalists in internal medicine residency training programs. In particular, the ability to recognize and distinguish patients with the two most prevalent rheumatic disorders, rheumatoid arthritis and osteoarthritis, must be taught to generalists more effectively by rheumatologists. PMID- 7886521 TI - Esophagopleural fistula: a complication of photodynamic therapy. AB - Mesothelioma of the pleura remains an incurable disease for which novel treatments are being investigated. One of these is intraoperative photodynamic therapy (PDT), using the principle of cell cytotoxicity produced by light activated sensitization. We report a complication of this therapy that defined the maximal tolerated dose of PDT, ie, esophagopleural fistula, in two consecutive patients who had received the same dose of PDT at the time of extrapleural pneumonectomy. PMID- 7886522 TI - Hospital-based alcohol and drug specialty consultation service: does it work? AB - The goals of this report are to describe the development of an inpatient-based alcohol and drug abuse consultation service in a university hospital. At the University of Wisconsin Hospital, we collected data on baseline diagnosis, health services, and costs for inpatients who received such a consultation in 1992-1993 (n = 1,098, 3.5% of all admissions). Follow-up interviews were conducted on a sample of 175 subjects. At the initial assessment, 65% were nicotine dependent, and 50% met criteria for alcohol dependence, 19% for alcohol abuse, 13% for alcohol and drug abuse/dependence. The average cost to patients for a consultation was $220. At the 6-month follow-up interview (n = 175), 42% of the subjects reported complete abstinence, 70% reported reductions in use, and 56% participated in an alcohol and drug treatment program. An inpatient-based alcohol and drug abuse consultation service provides a critical benefit that has not previously been offered in most academic medical centers. PMID- 7886523 TI - Are postoperative complications related to resident sleep deprivation? AB - This real-world study compares the outcome of surgery and the sleep-deprivation status of the resident surgeon. Residents who operated the day after a 24-hour on call period were considered sleep deprived; all other resident surgeons were considered non-sleep-deprived. We retrospectively reviewed data on 6,371 surgical cases and identified 351 postoperative complications. The complication data were analyzed using logistic regression analysis, with outcome being the presence or absence of surgical complications. No statistically significant change in complication incidence was noted when the resident surgeon was sleep deprived. PMID- 7886524 TI - Pentobarbital sedation for patients in the pediatric intensive care unit. AB - We present our experience with pentobarbital for sedation during mechanical ventilation in six infants when fentanyl and midazolam failed. The patients ranged in age from 2 to 17 months and in weight from 3.0 to 11.4 kg. Before the switch to pentobarbital, the maximum doses of fentanyl ranged from 7 to 13 micrograms/kg/hr and the midazolam infusions, from 0.2 to 0.4 mg/kg/hr. Pentobarbital was administered as a bolus dose followed by a continuous infusion. The hourly infusion rates ranged from 1 to 4 mg/kg. Adequate sedation was achieved in all six patients. In the four patients who required neuromuscular blocking agents, their use was discontinued after pentobarbital was given. The antihypertensive agents (diazoxide and nitroprusside) required by the two patients receiving extracorporeal membrane oxygenation were also discontinued after pentobarbital administration. Although we continue to use fentanyl and benzodiazepines as first-line drugs for sedation, pentobarbital may be an effective alternative when these agents fail. PMID- 7886525 TI - Impact of unfunded research in medicine, pathology, and surgery. AB - The impact of unfunded medical research (ie, research conducted with no visible means of support) has received scant attention. In this study, we counted research contributions from the 10 most-cited journals in the fields of internal medicine, pathology, and surgery. Ten consecutive articles, excluding case reports and review articles, for the years 1987, 1989, and 1991 were sampled from each of 10 journals for the three areas of medicine. Unfunded articles accounted for the majority of contributions (60% of pathology articles, 62% of internal medicine articles, and 74% of surgery articles). In 1987, funded research articles published received somewhat more citations (2,961) than unfunded research articles (2,368). Among articles supported by an NIH grant, the first author of the article was seldom the grant's principal investigator (38.6%, 26.9%, and 16.7% of funded articles by pathologists, internists, and surgeons, respectively). These results indicate that unfunded research plays a major role in medical research. PMID- 7886526 TI - Cold pressor test as a predictor of the severity of hypertension. AB - This report examines the cold pressor test (CPT) as it relates to the severity of hypertension. A total of 123 hypertensive patients were studied by physical examination, retinal funduscopy, chest roentgenogram, electrocardiogram, blood urea nitrogen measurement, and urinalysis. Causal and valid basal resting blood pressure determinations were made, followed by immersion of one hand in ice water for 2 minutes. All 21 patients with arteriosclerotic, 78 with essential, and 24 with renal hypertension had hyperreactive responses to the CPT (> 20/20 mm Hg) as compared with the normotensive subjects. The CPT-induced increase in diastolic pressure was significantly higher in hypertensives with left ventricular hypertrophy (LVH). CPT responses were also greater in hypertensives with higher degrees of retinopathy. These findings indicate that the diastolic rise on cold pressor testing can be used as a measure of severity of hypertension, especially in the presence of LVH and severe retinopathy. The CPT is inexpensive and noninvasive and can aid the clinician in managing the hypertensive patient. The CPT may also be useful as a predictor of complications of hypertension in selected individuals. PMID- 7886527 TI - Bilateral synchronous testicular germ cell cancer. AB - Bilateral synchronous testicular cancer is a rare occurrence usually associated with similar histologic findings in each testicle. We describe eight patients with bilateral synchronous testicular germ cell cancer, of whom four had dissimilar histologic findings. Contralateral disease in three patients was identified only by testicular ultrasonography or intraoperative exploration of the contralateral testicle, and in two cases by palpation 6 months after identification of the primary cancer. Treatment was determined by conventional staging and five of eight patients have remained free of recurrent disease. PMID- 7886528 TI - Blood specimens from patients referred for cytogenetic analysis: Vanderbilt University experience from 1985 to 1992. AB - Cytogenetic records were examined from consecutive nononcology blood specimens from 2,821 patients referred for cytogenetic services to Vanderbilt University Medical Center, Nashville, Tenn, from January 1985 to December 1992. We grouped the records according to reasons for referral and diagnoses. The most common reasons for referral were history of multiple abortions/miscarriages (23.3%), possibility of chromosomal abnormality (18.8%), and possible presence of the fragile X syndrome (15.6%). Overall, 2,418 (85.7%) patients were found to have normal chromosomes, and 403 (14.3%) patients were diagnosed with a cytogenetic abnormality. For example, 20 (5.4%) of the 373 males referred for the fragile X syndrome, or 1.4% of all males (20 of 1,428) excluding those with ambiguous genitalia, were diagnosed with this syndrome while 8 (2.1%) of the 373 males had a chromosome abnormality other than the fragile X chromosome. In addition, 85 (70.2%) of 121 males referred for Down syndrome had this syndrome, and only 53 (40.8%) of 130 females referred for Down syndrome had this diagnosis. This study should assist physicians in middle Tennessee and surrounding areas by increasing their awareness of the types and frequencies of cytogenetic diseases and by providing figures for comparison with other regions of the country. PMID- 7886529 TI - Frequency of uncommon abbreviations in medical journals. AB - Although the use of abbreviations not understood by the average reader is discouraged by journal editors, I nevertheless found that 43% of 147 articles published during June 1993 in eight general and surgical journals contained uncommon abbreviations. In 26 (18%) of the 147 articles, all the abbreviations and their explanatory decoding words appeared at the front of the article, either in the abstract or in the first paragraph. This up front position makes easier the reader's back-search. In 37 other articles (25%), at least one uncommon abbreviation was decoded somewhere in the body of the article. In 21 articles (14%) the uncommon abbreviations appeared in the concluding or summating paragraph(s) and the explanatory decoding words were buried in the body of the article, thus making difficult the reader's back-search. Corrective action might include (1) editorial and peer review enforcement of the "no nonstandard abbreviation" policy, which is easily done with computerized word processing; (2) tabulation of all abbreviations with their decoding words either just below the abstract at the front of the article or just above the bibliography at the rear; or (3) expansion of each abbreviation in a footnote at the bottom of the appropriate page. PMID- 7886530 TI - Long-term survival after autologous bone marrow transplantation for metastatic breast carcinoma. AB - A phase II study of doxorubicin (Adriamycin)-based induction chemotherapy followed by cyclophosphamide/BCNU (CyBCNU) intensification and autologous bone marrow transplantation (ABMT) was conducted in 20 consecutive women with hormone resistant metastatic breast cancer referred to our center. Of these 20 women, aged 24 to 56 (median age, 41), 9 had complete remission and 11 had partial remission after induction chemotherapy. Predominant sites of metastases included liver (5), lung (4), bone/bone marrow (5), and soft tissue (6). The dose of cyclophosphamide was 160 mg/kg and the dose of BCNU, 600 mg/m2, followed by infusion of a mean 2.30 x 10(8) nucleated marrow cells per kilogram of body weight. All patients achieved durable engraftment. Three patients remain disease free at 62+, 67+, and 73+ months; two of these were in complete remission before ABMT. Actual relapse-free survival at 5 years is 15% and median survival from ABMT is 17 months. Induction chemotherapy followed by CyBCNU intensification in metastatic breast cancer can achieve prolonged relapse-free survival in 15% of patients, some of whom may be cured. PMID- 7886531 TI - Technetium Tc 99m sestamibi scan for localizing abnormal parathyroid glands after previous neck operations: preliminary experience in reoperative cases. AB - We used technetium Tc 99m sestamibi for successful preoperative localization of abnormal parathyroid glands in nine patients with hyperparathyroidism and a history of neck surgery. The intraoperative and pathological findings were correlated with the preoperative technetium-sestamibi scan results. These nine patients had had 13 previous neck operations, two for thyroid disease, and 11 for hyperparathyroidism. In the two operated on for thyroid disease, the 99mTc sestamibi scan localized a parathyroid adenoma. In one patient, the three remaining hyperplastic parathyroid glands were localized using 99mTc-sestamibi scan. The other six patients had 10 operations for hyperparathyroidism; the 99mTc sestamibi scan localized the remaining parathyroid glands causing hypercalcemia. In this preliminary experience, the 99mTc-sestamibi scan localized all the abnormal parathyroid glands causing hyperparathyroidism in patients who had previously had neck surgery. PMID- 7886532 TI - Brain imaging in AIDS. AB - Although central nervous system (CNS) involvement is common in the population with acquired immunodeficiency syndrome, the presenting neurologic signs and symptoms are often vague and nonfocal. This represents a significant diagnostic challenge for the primary care physician. Cross-sectional imaging now plays an important role in the diagnosis of pathologic processes involving the brain in HIV-infected patients. Involvement of the brain with atypical viruses, parasites, fungi, and neoplasms is more prevalent in AIDS patients. On identification of a brain lesion, it is the role of the imager to characterize it in an attempt to provide a limited differential diagnosis. We review the imaging findings of the pathogens that most commonly affect the brain in AIDS patients. PMID- 7886533 TI - Cefprozil, a new cephalosporin: its use in various clinical trials. AB - Cefprozil is a new oral cephalosporin with a broad spectrum of activity against a wide range of aerobic gram-positive and gram-negative organisms, as well as certain anaerobic bacteria. Cefprozil has demonstrated good stability in the presence of beta-lactamase-producing organisms, a common cause of bacterial resistance with many older beta-lactam antibiotics. The relatively long half-life of cefprozil and its sustained duration in tissue (as measured by skin blister fluid concentrations) support once- or twice-daily dosing. Cefprozil is well tolerated and has a low incidence of adverse events. A review of clinical studies that evaluated cefprozil for the treatment of otitis media, sinusitis, pharyngitis, tonsillitis, lower respiratory tract infections, skin and skin structure infections, and urinary tract infections is presented in this article. In multicenter clinical trials, cefprozil was found to be comparable or superior to frequently prescribed antibiotics, including other cephalosporins, in terms of its safety profile and its bacteriologic and clinical response rates. PMID- 7886534 TI - Suppression of cell-mediated immunity in hypothyroidism. AB - A 71-year-old man had severe hypothyroidism, chronic autoimmune thyroiditis, and bacteremia due to Edwardsiella tarda. Review of the literature identified the hypothesis that E tarda infections may occur more frequently in immunocompromised patients. Previous animal studies have shown decreases in lymphocyte function during hypothyroidism, with return of normal lymphocyte function during euthyroid states. Therefore, lymphocyte transformation studies were obtained, demonstrating severe decreases in our patient's lymphocyte function. Except for chronic autoimmune thyroiditis, other immune system abnormalities were excluded. Serial lymphocyte transformation studies showed gradual improvement in lymphocyte function during gradual return to euthyroid state. Possible pathophysiologic mechanisms for these findings will be reviewed. PMID- 7886535 TI - Group B streptococcal vertebral osteomyelitis with bacteremia. AB - Group B streptococcal vertebral osteomyelitis is rare in adults. Osteomyelitis due to this organism is in general related to contiguous infections, recent surgery, or peripheral vascular disease. All reported cases of group B streptococcal vertebral osteomyelitis, however, have had no association with these predisposing factors and have usually been presumed to be of hematogenous origin, though bacteremia has never been demonstrated. Here we describe a 45-year old intravenous drug abuser who had vertebral osteomyelitis and bacteremia. We conclude that the vertebral osteomyelitis in this patient was hematogenous, as shown by bacteremia, and most likely resulted from intravenous needle use. PMID- 7886536 TI - Cocaine-induced ischemic cerebral infarction mistaken for a psychiatric syndrome. AB - We present the case of a 39-year-old woman who developed an ischemic cerebral infarction after using cocaine. Initially the patient was thought to suffer from a psychiatric disorder, and a computed tomography (CT) scan at the time of admission was entirely normal. Further evaluation of the patient by staff on the Psychiatric Unit led to the suspicion that she had suffered a stroke. A repeat CT scan on the third hospital day showed a large infarction in the left middle cerebral artery territory. We discuss the diagnosis of cerebral infarction with subtle presentations due to cocaine use. PMID- 7886537 TI - Vaginal evisceration. AB - An 89-year-old woman had small intestinal prolapse through the vagina while straining at stool. She had had a vaginal hysterectomy 24 years earlier. Resuscitation, reduction, and repair resulted in survival. PMID- 7886538 TI - Prolonged survival in carcinomatous meningitis associated with breast cancer. AB - We describe a patient who survived for more than 7 years after the diagnosis of meningeal carcinomatosis associated with breast cancer. Meningeal carcinomatosis occurs in 1% to 5% of patients with breast cancer. The median survival ranges from 3 to 7 months, but most reports include a small number of patients who survive considerably longer, with up to 11% surviving more than 1 year. Early diagnosis, aggressive treatment of neurologic involvement, limited systemic tumor burden, and varied rates of progression are factors that may relate to extended duration of survival in these patients with breast cancer. Our patient, with a hormonally responsive adenocarcinoma of the breast and without systemic metastases, illustrates that meningeal carcinomatosis, like other forms of breast cancer metastasis, can run an indolent course. In such patients the delayed sequelae of therapy for metastasis to the central nervous system can profoundly influence the course of the illness. PMID- 7886539 TI - Tuberculous otitis media. AB - Tuberculous otitis media (TOM) is a rare cause of chronic suppurative infection of the middle ear and mastoid. The increasing incidence of tuberculosis in the United States may be associated with more cases of TOM than recognized previously. Patients typically have a chronic tympanic membrane perforation and ear drainage associated with progressive and profound hearing loss. The correct diagnosis starts with consideration of the disease in a patient with a chronic middle ear infection that is unresponsive to routine therapy. TOM should be strongly considered in patients with known or suspected tuberculosis and a chronic ear infection; however, the lack of evidence of tuberculosis elsewhere does not exclude the possibility of TOM. Appropriate evaluation for TOM includes a chest film, purified protein derivative (PPD) skin testing, and smears or cultures of otic secretions for mycobacteria. Operative biopsy may be required. Facial nerve paralysis is highly suggestive of TOM. Medical therapy with antituberculous drugs is usually effective, and surgery is rarely needed. PMID- 7886540 TI - Bilateral endobronchial non-Hodgkin's lymphoma. AB - Pulmonary involvement with non-Hodgkin's lymphoma, while well recognized, is less common than with Hodgkin's lymphoma. Endobronchial non-Hodgkin's lymphoma is even rarer and usually occurs in the presence of disseminated disease. We present a case of bilateral endobronchial non-Hodgkin's lymphoma. PMID- 7886541 TI - With all due respect. PMID- 7886542 TI - Does normalization of blood glucose reduce the complications of diabetes? PMID- 7886543 TI - Malingered pregnancy. PMID- 7886544 TI - Pseudothrombophlebitis in neuropathic arthropathy of the shoulder. PMID- 7886546 TI - Proceedings of the Asian Pacific Congress on Bleeding Disorders and Transfusion Medicine. Impact on hospital services and health care. Bangkok, Thailand, May 10 15, 1992. PMID- 7886545 TI - Unilateral adrenal hyperplasia. PMID- 7886547 TI - Acquired bleeding disorders: bleeding in obstetrics and surgery. AB - Hemorrhage continues to be the leading cause of maternal mortality and morbidity throughout the world. In England and Wales from 1970-87 hemorrhage, including ectopic pregnancy, was a major factor in over 40 maternal deaths. In the majority of deaths the care was substandard. In 70% of obstetric deaths from hemorrhage defective hemostasis contributes to the bleeding. Inappropriate correction of hypovolemia, failure to recognise and treat coagulation failure, and failure to control traumatic bleeding are the main causes of preventable death. In developing countries, cross matched blood and blood products may not be readily available. Surgical intervention should be preceded or accompanied by correction of the hemostatic defect with fresh frozen plasma and if necessary platelet concentrates. Teamwork with experienced staff is the essence of successful management of severe hemorrhage in obstetrics and surgery. A protocol should be agreed between medical nursing and laboratory staff for dealing with massive blood loss. PMID- 7886548 TI - Exchange transfusion therapy in severe complicated malaria. AB - Nine cases of severe complicated falciparum malaria treated by exchange transfusion were studied. Eight patients survived and one patient died. Multisystemic complications were found in all cases. The CNS complications, acute renal failure, pulmonary insufficiency, jaundice, bleeding, sepsis, and DIC were found in 9, 7, 5, 7, 2, 4 and 1 cases, respectively. The fatal case presented with severe multisystemic complications together with 40% parasitemia. In eight survivors, whose parasitemia ranged from 0.3%, to 90%, had milder degrees of systemic complications. With the use of blood exchange 10-15 units, the parasitemia was decreased to less than 5% within 24 hours in all expect one who had parasitemia 90%. In comparison with the other 10 matched non-exchanged patients, there was no significant difference in survival rate between these two group (89% vs 80%). However, in the patients with ARDS the survival rate in the group who received the exchange transfusion therapy was superior (75% vs 0%). The exchange transfusion therapy is therefore strongly recommended in the treatment of malarial patients who present with parasitemia > 30% and severe systemic complications, particularly those who have severe acute renal failure or have lung complications. The amount of blood used for exchange transfusion should at least 1.2 times the blood volume for rapid removal of parasites and toxic metabolites from the circulation. PMID- 7886549 TI - Hemophilia with factor VIII and factor IX inhibitors, incidence, bleeding problems and management. AB - Among 117 cases of hemophilia, there were 7 hemophilia A and 2 hemophilia B with factor VIII and factor IX inhibitors diagnosed at the Department of Pediatrics, Siriraj Hospital, Bangkok, Thailand. The overall incidence of hemophilia with inhibitors was 7.7%. Eight cases (6 hemophilia A. 2 hemophilia B) were severe hemophilia and 1 moderate hemophilia A. The average age of the inhibitor detection was about 5 years. Of the 9 cases, 7 had high inhibitor titers and 2 had low inhibitor titers. The frequency of bleeding problems before and after inhibitor detection were not different. The bleedings included hemarthrosis, mucosal bleed, hematoma, oozing from wound, hematuria and intracranial hemorrhage. The treatment of hemarthrosis in hemophilia A with low inhibitor titers was the combination of short course of prednisolone and single large dose factor VIII. In high inhibitor titer patients with acute hemarthrosis (both hemophilia A and hemophilia B), the treatment consisted of prednisolone short course and single high dose of PCC. For bleeding control in both high and low inhibitor titer with mucosal bleeds, oozing from wounds, central nervous system bleeding and hematuria, the combination was used of high dose factor VIII or factor IX for 2 days, and tranexamic acid, prednisolone, cyclophosphamide were required. In life-threatening hemorrhage and surgical operation, plasmapheresis and large dosage factor VIII or factor IX were the treatment of choice. All supportive measures were also important in every case of mucosal bleeds, wounds and surgical operations. The result of treatment revealed one death from massive intracranial hemorrhage and 8 survivals, with joint contracture in 2 cases. All still have inhibitor detected, but in low titer. PMID- 7886550 TI - Management and surveillance of the hemophiliacs at the National Institute of Hematology and Blood Transfusion of Vietnam. AB - Surveillance and management 295 times of 29 hemophiliacs was carried out from 1985 to 1990. Among them, 113 were hospitalized, 103 with bleeding and 5 for prevention. Joint bleeding was the most frequent (46.96%), thereafter nose bleeding and bleeding from the gum, the mouth and mucous membrane (15.53%). Hemophiliacs having inhibitors to factor VIII were 13.79%. Fresh frozen plasma, cryoprecipitates, traditional medicine were used in the treatment. The effects of cryoprecipitates were shown to be better. The traditional medicine gave hope for prevention. PMID- 7886551 TI - Evidence of vitamin K deficiency in cord blood. AB - The prevalence of vitamin K deficiency in the newborns delivered at Siriraj Hospital was studied. The prolongation of one stage prothrombin time and the presence of PIVKA-II (non carboxylated prothrombin antigen) in cord blood were interpreted as the secondary change from vitamin K deficiency state. The most reliable method to diagnose vitamin K deficiency is the detection of vitamin K level in plasma which is not yet available in Thailand. Although the prevalence of vitamin K deficiency in the newborns from our data is not high, only 0.6%, it is shown that some of the apparently normal newborn infants may have bleeding problem from vitamin K deficiency in both newborn and early infancy periods. So, the correction of this deficiency by administration of vitamin K to all newborns is appropriate and reasonable decision. PMID- 7886552 TI - Risk factors of bleeding diathesis secondary to low prothrombin complex level in infants: a preliminary report. AB - Twenty infants aged 2 weeks to 3 months with the diagnosis of bleeding disorder secondary to low prothrombin complex level were studied. Sixty children of the control group were matched to the cases by age +/- 2 weeks, sex and race. The ratio of boys to girls was 2.3:1. The median, mean, and range of age of the cases and controls were 43.5 days, 43.7 days, 21-73 days and 43.5 days, 46.8 days, 26 28 days respectively. Most of them were pale with a mean hematocrit of 23.55%. The partial thromboplastin time and prothrombin time were markedly prolonged. The means of vitamin K dependent coagulation factors II, VII, IX and X were 1.10%, 5.87%, 2.86%, and 4.47% of adult activity, respectively. The clinical manifestations related to the bleeding of the cases were drowsiness and convulsion (95%), pallor (85%), and apparent bleeding (10%). The sites of the bleeding were demonstrated in the cranial cavity (95%), gastrointestinal tract and oral cavity (15%), and skin (5%). Nineteen patients with intracranial hemorrhage had bleeding in the subdural space (79%), intracerebral (42%), intraventricular (32%), and subarachnoid space (5.2%). The mortality rate and permanent brain damage occurred in 10% and 45%, respectively. Only 45% of the cases recovered normally. The permanent neurological sequelaes were hemiparesis (44.4%), microcephaly (33.3%), convulsive disorder (33.3%), mental retardation (33.3%), spasticity (22.2%), and hydrocephalus (11.1%). Breast feeding alone up to the day of study (OR = 7.0, p < 0.005) was found to be a significant risk factor for bleeding in these infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886553 TI - Hemostatic abnormalities in snake bite. PMID- 7886554 TI - Evaluation of donor self exclusion program. AB - Donor self exclusion is a low technology procedure to avoid blood donations from the high-risk groups for HIV infection. This strategy has been widely used in western countries to reduce the risk of transfusion associated AIDS. At Ramathibodi Hospital, we conducted a study on donor self exclusion program during March-December 1991. It was found 2.60%-6.55% (mean = 4.59%) of a total of 4,286 units of blood that were from the donors who indicated that their blood may not be safe for transfusion while the rest of them declared that their blood was safe based on sexual behavior during the past 3 months and the history of intravenous drug use. Among 202 units of unsafe blood, there were 1 (0.49%) positive for HIV Ag, 7 (3.46%) for anti-HIV, 5 (2.48%) for anti-HCV, 10 (4.95%) for HBsAg and 6 (2.97%) for VDRL while there was no HIV-Ag detected in 4,084 units of safe blood but 19 (0.46%) were positive for anti-HIV (p < 0.05), 65 (1.59%) for anti-HCV, 219 (5.36%) for HBsAg and 56 (1.37%) for VDRL. It was clearly demonstrated in this study that confidential self-exclusion or HIV-Ag testing would have eliminated this HIV-Ag reactive unit in the "window period" from transfusion, while the syphilis screening would not have had any value as a surrogate marker. However, self-exclusion programs are likely to prove too non-specific and need more time to educate the donors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886555 TI - Six cases of seroconversion of human immunodeficient virus (HIV) antibody post transfusion in HIV seronegative bloods. AB - Seroconversion of human immunodeficient virus (HIV)-antibody post blood transfusion has been reported (Jett et al, 1983; Cumming et al, 1989). We report here, six hematologic patients who became HIV-antibody positive after receiving HIV seronegative blood and blood components during their illness. There were three cases of acute non-lymphocytic leukemia, one thalassemia, one dyshemopoiesis and one hemophilia A. Thus, the risk of acquiring HIV infection from transfusion remains, despite the routine serological screening of donated blood by HIV ELISA tests. So the laboratory screening of blood should be improved by using more sensitive and specific antibody kits, including the use of HIV antigen testing, which have been reported to be useful in the diagnosis of patients with the early HIV infection. PMID- 7886556 TI - Risk of transfusion associated AIDS by seronegative blood in Thailand: a multicenter report. AB - Prevention of transfusion associated AIDS (TAA) in Thailand began in 1986 when the HIV infection started to be sharply increased among the general population. The retrospective anti-HIV screening in various blood donor populations by The National Blood Center (NBC) revealed a seroconverted prisoner. Then the use of prisoners, prisoners' blood was not recommended from 1986. In April 1987, the first case of TAA was disclosed. Five months later, anti-HIV screening in all units of blood was firstly introduced at Ramathibodi Hospital (RH) and NBC. From 1989, anti-HIV screening in all units of blood is mandatory nationwide by Ministry of Public Health. Despite the anti-HIV screening, TAA cases transmitted by seronegative blood were gradually reported. Among many Medical Centers, there were 9 and 18 cases of TAA recorded from Chiang Mai and Bangkok areas respectively, since 1985. In addition, several new seroconverters were observed among voluntary blood donors. All of this evidence indicates the existence of blood donation during the early stage of infection, the so-called "window period". At present, HIV-P24 antigen ELISA seems to be the only available technique for mass screening. In 1990, NBC successfully performed a retrospective study on HIV-Ag ELISA screening by obtaining the prevalence of 1/10,000 units of blood. At the same period of time, in RH prospective study, a unit of blood with HIV-Ag only was detected when 3432 units of blood were screened. The HIV-Ag ELISA screening was then performed on every unit of blood routinely since Aug 12, 1991 at RH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886557 TI - Prothrombin time and partial thromboplastin time as a predictor of bleeding in patients with dengue hemorrhagic fever. AB - Eighty-nine pediatric patients admitted at the University of Santo Tomas Hospital from June to December 1992, with the clinical diagnosis of dengue hemorrhagic fever (DHF) were studied with the following objectives: To determine the possible use of hematocrit, platelet count, prothrombin time (PT) and partial thromboplastin time (PTT) as predictors of bleeding and outcome in patient with DHF. The following were established: PTT can be an index in predicting bleeding in DHF. The tendency to bleed is greater with prolongation of > 30 seconds; platelet count can be a predictor of mortality, with death six times greater among those platelet count < 50,000/microliters than those whose platelet count was > 50,000/microliters. PT can also predict bleeding in patients with DHF. PMID- 7886558 TI - Laboratory assessment of thrombolytic therapy in acute myocardial infarction. AB - Hemostatic profiles and cardiac enzymes were studied in 55 acute myocardial infarct (AMI) patients to assess SK and rt-PA therapy. Hypofibrinogenemia occurred 85% in SK group and 55% in rt-PA group with high FDP and D-Dimer, indicating systemic fibrinogenolysis and local crosslinked fibrin clot lysis. The incidence of bleeding in SK and rt-PA groups combined with anticoagulants were the same but lower in rt-PA with antiplatelet. The mean FDP was significantly higher in the bleeding group (p < 0.01). Cardiac enzymes: CK, CK-MB peak values indicated reperfusion were 26.6%, 60% and 90% in conventional, SK and rt-PA therapy, respectively. Early and late occlusion did not occur either in SK or rt PA followed by anticoagulants. Late occlusion was found in patients treated with rt-PA and antiplatelet. Mortality rate was 20% in conventional therapy. PMID- 7886559 TI - Levels of plasma fibrinopeptide-A during surgery and the severity of the operation. AB - There is evidence to suggest that the rise of fibrinopeptide A (FPA) during surgery is influenced by tissue thromboplastin released during tissue damage. To investigate whether FPA correlates with the severity of the damage of the operation, 39 patients were recruited and venous blood samples were taken pre operatively, during skin incision, during bowel manipulation and post-operatively for the assay of FPA. The operations are grouped as minor (A), moderate (B), major (C) and very major (D). The peak FPA levels occurred during bowel manipulation in every degree of operations, and ranged between 6.0 to 22.2 pmol/ml. There was a tendency that peak FPA values rose according to the severity of the surgery, however only very major operations (D) are significantly higher when compared with minor operations (A) (p < 0.01). There was no good correlation between peak FPA levels and length of skin incision (p = 0.83, r = 0.04) as well as peak FPA levels and duration of operation (p = 0.90, r = 0.03). Significantly higher levels of FPA in very major operation (D) was due to more excessive tissue damage during surgery, while due to relatively minimal tissue injury, size of skin incision correlated poorly with FPA. PMID- 7886560 TI - Experience with factor VIII: C inhibitors and acquired von Willebrand's disease in an adult at Ramathibodi Hospital. AB - Eleven cases of acquired inhibitors against factor VIII: C and von Willebrand's factor (vWF) seen at the Department of Medicine, Ramathibodi Hospital from 1979 to 1991 were reviewed. Factor VIII: C inhibitor was found in 6 of 36 patients (17%) with hemophilia A (median age 18 years). Three patients each were weak (titer < 10 Bethesda units/ml), and strong antibody producers. Two cases of weak antibody producers had spontaneous disappearance of inhibitor, while all 3 strong antibody producers required specific treatment (corticosteroids, immunosuppressive drugs, and plasmapheresis). The inhibitor level temporarily declined in 2 patients, and disappeared in one. Spontaneous acquired inhibitor to factor VIII: C was seen in 3 patients. One each respectively had pemphigus vulgaris and bullous pemphigoid, autoimmune disease, and NIDDM. They were characterized by older age (median age 54 years), frequent skin and soft-tissue hematoma, but less hemarthroses. Inhibitor titer ranged from 15-280 Bethesda units/ml. Disappearance of the inhibitor after treatment with corticosteroids and immunosuppressive drugs were observed in all patients. Acquired von Willebrand's disease developed in 2 previously healthy patients. One patient was in the postpartum period, while the other had simultaneous acute viral hepatitis A infection. Both presented with the recent onset of spontaneous severe gingival bleeding, and demonstrated a prolonged bleeding time, reduced vWF:Ag (F VIIIR:Ag), and ristocetin cofactor (F VIIIR:vWF). Treatment with cryoprecipitate and corticosteroid resulted in remission of bleeding symptoms. Despite the rarity of these disorders, the recognition and proper management are of importance. PMID- 7886561 TI - Blood products usage in cardiac surgery. AB - Many patients undergo cardiac surgery with preexisting congenital and acquired coagulation defects. Almost all of these can be recognized and corrected preoperatively. In a complex operation involving the use of cardiopulmonary bypass (CPB), the significance of isolated changes in coagulation tests is difficult to assess. Many variable must be taken into consideration, including the coagulation and fibrinolytic systems, their natural inhibitors, and platelet number and function. CPB induces a variety of abnormalities of coagulation. These abnormalities do not always cause clinically significant bleeding. When they do, laboratory assessment and blood-component usage can usually correct the defect. The use of blood products is associated with allergic, viral, and hemolytic risks. Exciting advances have been made in the use of pharmacologic alternatives to blood products. Both Desmopressin (DDAVP) and aprotinin seem promising in this respect, but more investigation is needed on specific indications for these drugs and on the possible problems with a drug-induced thrombotic tendency. In the future, anesthesiologists and surgeons may look forward to more safe and effective therapy of bleeding in cardiac surgical patients. PMID- 7886562 TI - Factor VIII, factor IX and fibrinogen content in cryoprecipitate, fresh plasma and cryoprecipitate-removed plasma. AB - In order to provide accurate information for physicians, factor VIII, factor IX and fibrinogen content were determined in 40 bags of cryoprecipitate, fresh plasma and cryoprecipitate-removed plasma. A cryoprecipitate bag with a volume of 21.8 +/- 5.3 ml contained 139.5 +/- 42.9 units of factor VIII and 200.0 +/- 80.0 mg of fibrinogen. Fresh plasma with a volume of 208.0 +/- 22.5 ml contained 180.9 +/- 45.3 of factor IX, significantly higher than in cryoprecipitate-removed plasma. It was also found in this study that group O blood showed a significantly lower level of factor VIII. PMID- 7886563 TI - Cost effectiveness in screening of class I HLA antibodies in Thai pregnant women. AB - Fifty-seven sera obtained from pregnant women who attended antenatal clinic were screened for class I HLA antibodies by standard microlymphocytotoxicity test. The age ranged from 20 to 40 years (mean +/- SD = 30.4 +/- 5). The lymphocytes obtained from 98 HLA-typed persons were used as the panel which would include all common HLA-A and HLA-B antigens and as many rare antigens as possible. Eight out of 57 sera (14%) had HLA antibodies which reacted as follows: 3 sera had nonspecific antibodies, 3 sera had multispecific antibodies (B60 + B48 + B7, B60 + B61 + B13 and B51 + B35 + B53), one serum had a monospecific antibody (A2) and one serum was unidentified. The identified antibodies showed strong reactivity (r > 0.8). These sera will be used as HLA typing sera and exchanged with other HLA laboratories. The screening test for class I HLA antibodies in pregnant women attending the antenatal clinic is useful and practical. Several HLA antisera can be obtained at low cost. The cost of self-screening antisera was US$90/ml while the cost of commercial HLA typing sera is approximately US$250/ml, a factor to be considered by a new HLA laboratory with limited budget. PMID- 7886564 TI - Local hemostatic technic using a celluloid splint in bleeding disorders. AB - Controlling hemorrhage from dental treatment in bleeding disorder patients is one of the most serious procedures encountered by the dentist. In the Dental Division, Ramathibodi hospital, dentists use local hemostatic technics combined with replacement therapy, local hemostatic agents and antifibrinolytics in the management of bleeding disorders in dental patients, such as leukemia, ITP, hemophilia. Celluloid splints as an adjunct therapy is very beneficial in controlling hemorrhage in dental procedures as shown by 5 years experience with 278 patients. The advantages are: less expensive, lesser days hospitalized, better outcomes. Presently it is used as a routine technic in dental treatment. PMID- 7886566 TI - Donor recruitment and retention. PMID- 7886565 TI - Response of hemophilia A with bleeding to fresh dry plasma. AB - Fresh dry plasma (FDP) is a lyophilized form of fresh frozen plasma (FFP) which can be stored at 4 degrees C for one year. One bottle of FDP is prepared from 220 ml of FFP and contains FVIII: C 0.75 +/- 0.3 U/ml (mean +/- 1 SD). This study describes the clinical and laboratory response in 7 severe and 4 moderate hemophilia A patients. The age ranged from 7-17 years (mean +/- SD = 11.7 +/- 2.9 years). Either 12.4 ml/kg. FDP or 12.2 ml/kg FFP was transfused to the patients when they had bleeding episodes such as hemarthrosis, hematoma. 16 episodes of FDP and 12 episodes of FFP transfusion were studied. The bleeding could be effectively controlled by FDP or FFP except one patient who had physical therapy at 8 hours post FDP transfusion. The increment of FVIII:C was 14.1 +/- 5.3% at 30 minutes after FDP transfusion and 12.1 +/- 3.7% at 30 minutes after FFP transfusion. The recovery rate was 83.2 +/- 32.6% in FDP and 65.3 +/- 22.7% in FFP transfusion. The FVIII:C was decreased to 78.9 +/- 12.3%, 55.6 +/- 13% and 16.3% of the initial level at 2, 8, 24 hours after FDP transfusion respectively which were not statistically significantly different from FFP transfusion. No serious complication was found. FDP will replace FFP for the treatment of coagulation disorders such as hemophilia A. It is an useful alternative therapy which can be provided to the hemophiliac patients in the rural area in developing countries. PMID- 7886567 TI - Response of patients with bleeding disorder to DDAVP administration. AB - DDAVP has been shown to provide hemostasis in patients with bleeding disorder. Thirty-one episodes of intravenous DDAVP administration (0.3-0.4 microgram/kg) in 22 patients with bleeding disorder were studied. There were 13 patients with hemophilia A, 1 with type I vWD and 8 with inherited and acquired platelet dysfunction. The age ranged from 2.3-26 yrs (mean +/- SD = 10 +/- 4.8). None of the 3 severe hemophilia A patients responded to the treatment. Two out of five episodes in 4 moderate hemophilia A patients responded clinically and had minute increments of F VIII:C. Ten out of eleven episodes (91%) in 6 mild hemophilia A patients had good responses. The dental procedures for these patients were successfully performed without blood component transfusion. The increments of F VIII:C ranged from 1.5-6.8 folds over the baseline levels (mean +/- SD = 2.5 +/- 1.4). In addition, two episodes of epistaxis in a vWD patient responded excellently and one dental procedure was successfully performed by giving DDAVP. The increments of F VIII:C and vWF:Ag ranged from 2.8-12.5 and 2.9-8 fold over the baseline levels respectively. The prolonged bleeding times were shorten to 6.5-7 minutes. Only three out of eight episodes in 8 inherited and acquired platelet dysfunction patients showed temporary responses. The bleeding time responses did not correlate with in vitro platelet aggregation. PMID- 7886569 TI - The effect of prior transfusion history on blood donor anti-hepatitis C virus antibody. AB - In Japan, the major transfusion-associated disease is non-A, non-B hepatitis. We studied the relationship between transfusion history and blood donor antibodies to hepatitis C virus (HCV). The positive rate of antibodies to the HCV nonstructural protein (c100-3) depended on age and the time elapsed since transfusion. The anti-c100-3 ratio for subjects with transfusions made prior to 20 years ago was high. One quarter century ago, a change occurred in national blood policy from paid to non-paid voluntary donations. We also have studied the anti-HCV positive rate among donors with prior transfusion using a second generation HCV test kit which includes anti-HCV core antibody detection. The anti HCV positive rate for the second generation test was higher than that for the anti-c100-3 test. Introduction of the second generation test is therefore more useful in screening than the anti-c100-3 test for blood programs. PMID- 7886568 TI - Prevalence of cytomegalovirus antibody in Thai-northeastern blood donors. AB - The prevalence of cytomegalovirus antibody was studied in sera of 359 Northeastern blood donors with an age range of 17-59 years by ELISA for anti-CMV total antibody (anti-CMV). Anti-CMV was detected in 93.31% (335/359) of blood donors. The prevalence in males was 91.53% (227 in 248) while female donors showed 97.30% (108 in 111) positive for anti-CMV. The results demonstrated no statistical difference between sex and age. One-hundred and eighty serum samples with positive anti-CMV were reexamined for anti-CMV IgM antibody. Only one sample was found to be positive. This study suggested that CMV seronegative blood supply was very limited. Therefore leukocyte-depleted blood should be the method of choice for prevention of post-transfusion CMV infections in high risk recipients. PMID- 7886570 TI - HIV seroprevalence in hematologic patients other than hemophiliacs at Ramathibodi Hospital. AB - Recently there have been increasing reports of HIV infection acquired through transfusion of HIV seronegative blood in Thailand due to high incidence of HIV new infection in blood donors. Blood or blood components (BC) prepared from HIV seronegative blood donation pose significant hazards to recipients because of the risk of viremia during the "window period" of HIV infection. This paper presents the HIV seroprevalence in hematologic patients other than hemophiliacs who received multiple blood transfusion at Ramathibodi Hospital. The retrospective analysis was done on 167 patients: 132 thalassemia, 19 leukemia, 5 aplastic anemia, 5 ITP, 2 pure red cell aplasia, 2 congenital non spherocytic hemolytic anemia, 1 hereditary spherocytosis and 1 autoimmune hemolytic anemia patients, who received blood transfusion during January 1, 1987 till February 29, 1992 at the Department of Pediatrics, Ramathibodi Hospital. The number of blood or BC transfused in each patient was 1-154 units with the average of 23 units per patient per 5 years with a total 4,000 units. All were HIV sero-negative. Anti HIV screening was performed periodically in these patients about 1-2 times per year or as necessary. The results were HIV seronegative in all cases. The reason for negative results cannot be explained clearly. It should be noted that our thalassemic patients receive leukocyte poor blood and avoid a hypertransfusion program. Patients with other blood diseases received both whole blood and BC. The HIV contaminated blood in the window period was estimated to be 1:10,000 in Thailand which showed HIV antigen positive but antibody negative. These patients may be fortunately received HIV non contaminated blood. PMID- 7886571 TI - HIV seroconversion in Thai hemophiliacs up to 1991. AB - In Thailand, the anti-HIV screening in the donor blood was started in 1987 and was compulsory nationwide in February 1989. Sixty-six hemophilia A and 10 hemophilia B patients who received approximately six million units of factor VIII and IX in the form of fresh frozen plasma, frozen cryoprecipitate, cryoprecipitate removed plasma, fresh dry plasma and factor concentrate during 1976 to 1991 were tested for anti-HIV since 1987. The age ranged from 1-39 year (mean +/- SD = 15 +/- 7.3). The anti-HIV test was performed by ELISA and/or gel agglutination and confirmed by Western blot analysis. The patients would be checked 1-2 times per year and as necessary. A total of 174 tests for the first, second, third, fourth, fifth and sixth tests were studied in 76, 49, 27, 14, 5 and 3 patients respectively during 1987 to 1991. The prevalence of HIV seroconversion in the year 1987, 1988, 1989, 1990 and 1991 was 2.2% (1/45), 1.9% (1/53), 1.6% (1/63), 1.5% (1/67) and 3.9% (3/76) respectively. Three HIV seroconversion were found in the first, fourth and fifth anti-HIV test in 3 hemophilia A patients who received massive infusion of blood components during orthopedic corrective surgery. One case of HIV seroconversion found in 1987 was transmitted by HIV unscreened blood while 2 cases in 1991 by anti-HIV seronegative blood whose donors were in the window period of HIV infection. The prevalence of HIV seroconversion in Thai hemophiliacs is much lower than those in western countries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886572 TI - Plasmapheresis for the preparation of HIV free cryoprecipitate. AB - Single donor cryoprecipitate was prepared by blood cell separator for treatment of hemophilia A and von Willebrand patients to reduce a risk of transfusion associated HIV infection. A total of 7 plasmapheresis (range 1-1.5 plasma volume) was performed in 4 donors. Then fresh frozen plasma (FFP) was processed to cryoprecipitate and cryoprecipitate removed plasma (CRP). Donors were replaced with 0.9% normal saline solution (NSS) and 5% albumin for the first donation or their own CRP and 5% albumin for the second and third donation. After plasmapheresis total protein, albumin, IgG, IgA and IgM were below normal level in 71.43% (5/7), 14.3% (1/7), 28.57% (2/7), 14.3% (1/7) and 28.57% (2/7), respectively. All of these parameters returned to normal level within 3 days. Factor VIII:C was decreased after plasmapheresis in all donors and the low level of F VIII:C returned to normal within 24 hours. The donor was not exposed to any harmful effect. Donor reactions observed were mild. One donor was chilled due to unwarmed replacement solution. When this donor donated for the second time and was replaced with prewarmed replacement solution, no reaction was observed. We conclude that a preparation of single donor cryoprecipitate by plasmapheresis is safe and can reduce a risk of transfusion associated HIV infection. The donors are not at risk as the result of changes in the measured plasma protein and factor VIII:C level following plasmapheresis. PMID- 7886573 TI - The safe blood components for a hemophilia patient: a case report. AB - This study comments on safe blood components prepared for a 6 year old boy with hemophilia A (F VIII:C 1.8%). He has required blood transfusion since 10 months of age and started home therapy since 3 years of age. The utilized blood components were fresh dry plasma (FDP) prepared from 8-10 selected donors who were in good health and had no risk of blood-transmitted diseases. They were parents, relatives and friends with the age ranging from 30-45 years old. The FDP would be used after the donors had at least two subsequent negative tests for anti-HIV. In addition, cryoprecipitate collected from parents by plasmapheresis was started in 1990. Twelve to fifteen bags of cryoprecipitate were collected each plasmapheresis. The blood components prepared from the selected donors is an additional management to obtain the better quality of blood. Moreover, the role of parents taking the major responsibility in the recruitment of donors will minimize the shortage of blood donors. PMID- 7886574 TI - Experimental research on immunological activity of Polyactin A. AB - Polyactin A is a polysaccharide extracted from cultured alpha-Streptococcus No. 33 in the mouth. It is also known as alpha-glucomannan. According to clinical reports, Polyactin A is considered to be an immunological adjuvant with significant curative effect in chemotherapy of tumors. Immunological activities of Polyactin A were studied. When injected into mice at the dosage of 100 mg/kg for 4-5 consecutive days, Polyactin A can cause a marked increase in spleen weight and RFC in spleen, and it can antagonize the immunosuppressive actions of cyclophosphamide. Polyactin A can also increase phagocytosis of macrophages in the peritoneal cavity of mice. Phagocytotic ratio and phagocytotic index in the experimental group were greater than those in the control group. Phagocytotic ratio and phagocytotic index were respectively 63.5 +/- 8.3% and 1.02 +/- 0.05% in the Polyactin A treated group but were respectively 21.0 +/- 5.7% and 0.3 +/- 0.03% in the control group. The differences were significant (p < 0.05, < 0.01). Polyactin A had definite influence on the transformation test of lymphocytes and increased the transformation ratio of lymphocytes in vitro. The ability of Polyactin A to induce the transformation of lymphocytes into lymphoblasts was almost the same as that of PHA. These results suggest that polyactin A has a marked immunological activity, which is not entirely due to the role of large molecular weight polysaccharide. They provide direct evidence for the assumption that Polyactin A may be an immunological adjuvant, and it is experimentally confirmed that Polyactin A can protect the immunity of the organism. PMID- 7886575 TI - Immunoglobulins in acquired platelet dysfunction with eosinophilia. AB - Acquired platelet dysfunction with eosinophilia (APDE) is acquired bleeding diathesis associated with platelet dysfunction causing prolonged bleeding time. Most of them had eosinophilia. Various reports of the isolated cases had normal level of immunoglobulins but few had increased IgE. This report is different from others in that among 41 cases of APDE, it was found that most of them had normal levels of IgG, IgA, IgE but there was increased IgM in 95.1% of the cases. Increased in IgE was noticed in 7/24 cases (29.2%) and only half (3/6 cases) corresponded with eosinophilia. PMID- 7886576 TI - Inhibitors of factor VIII: detection and treatment. AB - Alloantibodies occurring in hemophiliacs is a side effect or repeated treatment and represents a severe complication. The induction of immune tolerance using one of the lower dose regimens should be attempted as soon as it is feasible as regimens started soon after the inhibitor appears may have greater success in inducing tolerance. If the hemophiliac with inhibitor hemorrhages, PCC for aPCC should be the first line of therapy since these concentrates can be given in the home setting. If the hemorrhage is severe and the anti-porcine inhibitor titer is low, the patient should be infused in a clinic or hospital setting with porcine factor VIII using increasing doses to achieve a circulating factor VIII level. Entry into clinical trials, such as those using rFVIIa should be encouraged. PMID- 7886577 TI - Pulmonary and platelet function in mild form of Hb H disease. AB - Pulmonary function abnormality, arterial hypoxemia and platelet hyperaggregation were commonly seen in severe or moderately severe thalassemic patients. In previous studies, these abnormalities were found in beta-thalassemia, beta thalassemia/Hb E disease and Hb H disease in 62, 40 and 52%, respectively. However these functional abnormalities in mild form of Hb H disease have not yet been reported. Pulmonary function test by using standard spirometry, platelet aggregation and arterial blood gases were performed in 23 children with mild form of Hb H disease, whose age ranged from 6-18 years (average 11 years), and hematocrit status was 30-40%. Mild to moderate degree of restrictive lung disorder was found in 48% of these patients, 5% had mild platelet hyperaggregation and none of these had arterial hypoxemia. This study showed that a pulmonary function defect was noted as one significant finding in thalassemic patients, being noted even in the very mild form and early age of life. This information will lead to further exploration of the pathogenesis of pulmonary function defects as well as their role is the patients' future health and prognosis. PMID- 7886578 TI - Platelet counts in thalassemic children before and after splenectomy. AB - Even though thrombotic risks in thalassemia patients from standpoints of platelet dysfunction and coagulation factors are controversial, they are in favor of thrombosis due to thrombocytosis. From the study of 74 cases of thalassemia in children, marked thrombocytosis occurred during day 8 to 4 months during which one should be aware of the thrombosis. However, none of thalassemia children had acute thrombosis even at platelet counts of 1.6 million/microliters. PMID- 7886579 TI - PF3 activity in normal subjects and beta-thalassemia trait. AB - Platelet factor 3 (PF3) is a platelet membrane component that plays an important role in the activation of the coagulation mechanism. Whenever platelet activation occurred, PF3 is released and participates in thrombin formation. Erythrocyte membrane fraction has also some PF3 like activity, and in abnormal erythrocyte membrane disorders, eg thalassemia, some of the membrane fraction accelerates platelet activation by increasing the PF3 activity. Formerly it was difficult to measure the PF3 activity in plasma. Recently a sensitive chromogenic test to determine the PF3 activity, which could detect the changes in PF3 activity with time, was introduced. This study was done to observe the effect of abnormal erythrocyte on platelet activation. The results obtained using the chromogenic method are the following: whole blood taken from normal subjects showed OD 0.11 +/- 0.06 at 0 minutes after blood collection and then increased significantly (p < 0.01) to 0.21 +/- 0.10 after 90 minutes, while the platelet count did not differ significantly (p > 0.05). Those results showed that there were some platelet activation after 90 minutes as seen by the increased PF3 activity, with no significant change in platelet counts. In beta-thalassemic trait subjects the PF3 activity in whole blood at 0 minutes did not differ significantly compared to the normal subjects, but after 90 minutes it was significantly higher (p < 0.01), OD 0.52 +/- 0.35. However the PF3 in platelet rich plasma at 90 minutes did not increase. The platelet count after 90 minutes was significantly decreased (p < 0.01) This result suggest that the increase in PF3 activity was caused by the role of the abnormal erythrocytes. PMID- 7886580 TI - Bernard-Soulier syndrome: a case report. AB - An adopted Thai girl has been followed at Children's Hospital, Bangkok, since she was 8 months old. The diagnosis of Bernard-Soulier syndrome was made, based on the clinical features of easy bruising, purpura, petechial hemorrhages and recurrent epistaxis. The abnormal laboratory tests included giant platelets with dark stained granules, mild to moderate thrombocytopenia, prolonged bleeding time, absence of ristocetin induced agglutination but normal ristocetin cofactor, factor VIII coagulant activity and von Willebrand factor antigen. These findings suggested the absence of glycoprotein Ib (GPIb) on the platelet membrane. The genetic transmission can not be evaluated in this patient. PMID- 7886581 TI - The behavior of transfused platelets in dengue hemorrhagic fever. AB - The transfusion of platelet concentrate has been proved as a valuable clinical procedure in the management of bleeding in dengue hemorrhagic fever (DHF). This paper described the behavior of transfused platelets as platelet response and platelet increment in DHF patients with and without shock. Fifteen patients with DHF were studied, aged 2 to 12 years old. All had bleeding manifestation, ie GI, skin, nose or gum. Fresh human platelet concentrate was transfused to 5 non-shock cases and 10 shock cases with different dosages as the low dose (0.15-0.23 U/kg) and high dose (0.28-0.46 U/kg). The cessation of active bleeding was noted by clinical observation or hematocrit determination. The degree of elevation of the circulating platelets tended to vary inversely to the degree of shock and directly to the amounts of platelets infused. The survival of transfused platelets was very short in shock cases, about few hours to one day. This may be due to many factors: platelet plug to injured vessels, immune complex reaction, trapping of platelets to the poor circulation area, rapid utilization and destruction of platelets by injured vessels or virus and slow circulation promoting platelet adhesion. PMID- 7886582 TI - A new method for factor VII deficient substrate preparation and coagulation studies in malaria. AB - A simplified technique using DEAE-cellulose chromatography for the preparation of factor VII deficient substrate was developed in order to reduce the high cost of individual factor VII assay in the routine coagulation laboratory. The substrate prepared from cryo-removed human and bovine plasma had a high correlation (r = 0.9929) with two of the most popular imported commercial substrates available (DADE, Ortho). When compared several other imported commercial substrates of equal quality, the prepared substrate was 3,000 to 6,000 times cheaper. Using the prepared factor VII deficient substrate along with other commercial substrates available, two hundred and fifty patients with malaria (fifty cases of P. vivax and two hundred cases of P. falciparum) were studied for coagulation and fibrinolysis abnormalities. Only P. falciparum infections showed prolonged PT and aPTT which correlated with the degree of parasitemia (r = 0.0972). Factors V, VII, and IX were the most sensitive parameters in the expression of coagulation defects and most coagulation abnormalities were due to liver involvement. Plasmin activity was normal in P. vivax patients but it was significantly increased in P. falciparum patients with > 5% parasitemia. Only two of the complicated cases of P. falciparum patients showed the evidence of DIC. PMID- 7886583 TI - Disseminated intravascular coagulation in children: diagnosis, management and outcome. AB - A retrospective study of 46 patients with disseminated intravascular coagulation (DIC) is reported. Twenty three patients were neonates with a mean age of 6.7 days (SD = 10) and twenty three patients had a mean age of 2.4 years (SD = 3.3). The ratio of males to females was 1:1. Thirty-two out of 46 patients (69.6%) had underlying diseases such as congenital abnormalities in cardiovascular and gastrointestinal systems. The diagnosis of DIC was suspected in the critically ill patients who had certain conditions that could trigger DIC. The laboratory findings revealed red blood cell fragmentation 93.4%, thrombocytopenia 95.5%, prolonged coagulogram 71.9% and increased FDP 74%. The management included treatment of underlying diseases, identification and relief of triggering conditions, correction of coagulopathy and supportive care. In terms of infection, appropriate antimicrobial agents were administered. Exchange transfusion was performed in 21 patients and heparin was given to patients with major vessel thrombosis such as renal vein thrombosis. Inspite of the above mentioned managements, the overall case-fatality rate was 52%. Factors related to high case-fatality rate were accompanying fatal diseases, shock, hemorrhage or thrombosis. There were no correlations between fatality rate and age, sex, triggered conditions or exchange transfusion. There is a need to establish an effective treatment that can stop the rapid ongoing process of DIC in order to achieve a better outcome in patients with DIC. PMID- 7886584 TI - The effect of Norplant on some hemostatic parameters in Indonesian women. AB - Many reports have indicated that oral contraceptives can increase the incidence of thromboembolic disorders. Norplant, an implant contraceptive containing levonorgestrel, has been developed recently. The aim of this study is to observe the effect of Norplant on some hemostatic parameters. The subjects in this study were divided into 5 groups. Group 1 (control) consisted of 25 female blood donors. Group 2 (N = 25), group 3 (n = 25), group 4 (n = 17) and group 5 (N = 20) consisted of subjects who had been using Norplant for 2, 3, 4, and 5 years, respectively. Prothrombin time, activated partial thromboplastin time, fibrinogen level, assay of F VII and X, antithrombin III activity, plasminogen activity, alpha 2-plasmin inhibitor activity and platelet aggregation test were done in all subjects. Our results showed that there was a significant difference (p < 0.05) on platelet aggregation induced by 10 microM of ADP between the control group and Norplant users for more than 2 years, while the other parameters did not differ significantly. It is concluded that 5 years users of Norplant did not alter blood coagulability, but increased platelet response to 10 microM of ADP. PMID- 7886585 TI - Hemogram in normal newborn babies with special reference to platelet count. AB - A prospective study was performed to verify the hemogram of 318 healthy fullterm newborn babies aged one hour to thirty days. The mean hemoglobin, hematocrit and reticulocyte count were between 17.6-17.9 g/dl, 52.2-53.4% and 5.7-6.7% in the first 72 hours of life. After that, they were decreased gradually approaching adult level at the later half of one month old. The white blood count at 12 to 24 hours was 18,482 +/- 6,600/microliters, gradually decreased to 9,817 +/- 2,496/microliters during 14 to 30 days. The ratio of immature to total neutrophils between 1-12 hours was 0.07 and 12 hour to 30 day was 0.04-0.05. The mean platelet counts in the first 72 hours was between (280 +/- 69) x 10(3)-(285 +/- 93) x 10(3)/microliters, it increased thereafter until 30 days old with a peak of 402 x 10(3)/microliters during 7-14 days. The platelet counts below 150 x 10(3)/microliters in the newborn period should be considered as thrombocytopenia. PMID- 7886586 TI - Lupus anticoagulant in Thai systemic lupus erythematosus patients. AB - In the past decade, interest in the potential clinical significance of lupus anticoagulant (LA) has grown tremendously. Recent reviews from the Western countries have found an average frequency of 34% for LA in patients with systemic lupus erythematosus (SLE). By using various laboratory procedures, namely, standard and diluted activated partial thromboplastin time, kaolin clotting time, tissue thromboplastin inhibition test and platelet neutralization test, we found the frequency of LA in 91 consecutive Thai SLE patients to be 17.5%, compared with 0.8% in the age-matched normal control population. The presence of LA was significantly associated with disease activity (p = 0.01). A statistically significant association was also observed between the presence of LA and convulsive disorders (p = 0.04), thrombocytopenia (p = 0.001) and autoimmune hemolytic anemia (p = 0.02). PMID- 7886587 TI - Dengue virus and endothelial cell: a related phenomenon to thrombocytopenia and granulocytopenia in dengue hemorrhagic fever. AB - Adhesion to endothelial cells by blood cells was assessed by measuring the cell number of each blood cell component in the supernatant after exposing blood cells to dengue-infected endothelial cells for 0, 10, 20 and 30 minutes. White blood cells, neutrophils, lymphocytes, platelets, and large lymphocytes or large unstained cells (LUC) preferentially bound to dengue-infected endothelial cells as compared to the control endothelial cells. P values were 0.0096 for total leukocytes and platelets, 0.006 for lymphocytes, and 0.001 for neutrophils and LUC. Monocytes basophils and eosinophils had no interaction with dengue-infected endothelial cells. The increased binding of neutrophil and platelet to endothelial cell may explain neutropenia and thrombocytopenia in DHF patients. PMID- 7886588 TI - Differentiation of platelets from red cell fragments using laser technology: comparison between splenectomized and nonsplenectomized thalassemic patients. AB - Platelets from 59 beta-thalassemia/hemoglobin E (beta-thal/HbE) patients (19 were splenectomized) and 97 normal individuals were studied using laser and computer analysis. Fragmented red cells of similar platelet volume were differentiated from platelets using laser inspection of the intracellular hemoglobin of the fragmented red cell. The patients had increased platelet count than normal cases at p < 0.0001 (nonsplenectomized, mean +/- SE = 32.4 +/- 21.9; splenectomized, 617.5 +/- 64.2; normal, 264.7 +/- 6.4 x 10(3) cells/dl). Splenectomized patients had greater platelet counts than nonsplenectomized cases (p < 0.0001). Numbers of small red cells, probably red cell fragments, markedly increased in nonsplenectomized patients. Increased heterogeneity in platelet size was demonstrated in the patients of both groups. The nonsplenectomized patients had significantly higher mean platelet volume than normal (p < 0.02) and splenectomized cases (p < 0.01). Increased platelet number and heterogeneity in platelet population may involve in pulmonary thrombosis in splenectomized patients. PMID- 7886589 TI - Surgical orthopedic correction of hemophilic hemarthrosis at Ramathibodi Hospital. AB - During 1982-1992, 15 major surgical orthopedic correction (SOC) were performed in 12 hemophiliacs. There were 11 synovectomy, 2 osteotomy, 1 currettage and suture wound, 1 release of multiple joint contracture and 1 removal of pseudotumour. During 1982-1989, frozen cryoprecipitate was entirely used for replacement therapy in 5 cases who had 7 SOC. During 1990-1992, 7 cases received SOC by using factor VIII concentrate (Emoclot or Profilate) alone or combined with cryoprecipitate in 8 SOC. Multiple surgical procedures could be performed by using factor VIII concentrates. The orthopedist could operate 3 joints in one setting ie right knee, left knee and right middle finger. There are many advantages of factor VIII concentrates over those of cryoprecipitate, especially in the aspect of HIV transmission by HIV seronegative blood products. The disadvantage is the extremely high cost of factor concentrates. PMID- 7886590 TI - An evaluation of a new gel system (ID-gel) for antibody screening and identification. AB - An evaluation of the new "ID-Gel System" (Diamed) for the detection of red cell antibody-antigen reactions was undertaken in the King Khalid University Hospital Blood Bank. Antibody screening was performed in 700 patient samples using both the conventional test tube (bovine albumin and LISS) techniques and the new ID gel technique. The results obtained were as follows: a) 70 antibodies of various types were detected by the bovine albumin technique. b) 98 antibodies were spotted by LISS. c) The ID-gel system detected 122 antibodies (17.43%) which included all those detected by the other two techniques. It was concluded that the ID-gel system is a far more sensitive technique than the conventional Blood Bank immuno-haematological tests. In addition, the ID-system has the further advantage of standardization of the test, shorter incubation time, no washing procedure and reduces the technologist time, effort and perhaps number. PMID- 7886591 TI - The value of HLA-ABC common typing tray in relation to bone marrow transplantation. AB - Bone marrow transplantation (BMT) is one of the most effective procedures to cure the previously uncured hematologic diseases. However, it is costly and HLA typing to select the compatible donors contributed to its cost. A total of 53 prospective patients for BMT and their 114 siblings were analyzed to evaluate the use of locally prepared HLA-ABC common typing tray (ABCCT) during Mar 1988-Mar 1992. The 16, 9, 7, 5, 5 and 12 patients were diagnosed as aplastic anemia, CML, thalassemia, ALL, ANLL and other blood diseases, respectively. It was found that 18 patients were HLA-identical (HLA-ID) with one of their siblings except one patient had 2 HLA-ID sibs. All of those who appeared to be HLA-ID were further tested for the HLA-ABCDR typings. It was observed that 16 (88.89%) of 18 patients and 17 (89.47%) of 19 sibs were confirmed as HLA-ID. After careful clinical screening, only 13 HLA-ID pairs were able to proceed to the mixed lymphocyte culture and confirmed their status of HLA-ID by this test. Finally, only 6 (46.15%) of 13 patients received BMT with a high rate of success, ie all patients have survived with bone marrow engraftment. Thus, ABCCT is very useful for related BMT. It was highly efficient to exclude HLA-non-ID and haplo-ID yet the cost and workload were greatly reduced. PMID- 7886592 TI - Rehabilitation and the role of the physical therapist. AB - Severe hemophilia patients suffer from joint and muscle bleeds. If not treated at once, they may cause chronic synovitis and arthropathy of joints and wasting and contractures of muscles. These impairments may cause disabilities and handicaps in daily life. Next to replacement therapy, physical therapy is also important: active muscle strengthening exercises, prevention and treatment of contractures and pain, functional training, physiotechnical applications. Furthermore, exercises and sports to prevent problems of the musculoskeletal system are mentioned. Indications for the use of orthotics and special shoes are described. PMID- 7886593 TI - Hypercoagulation in diabetes mellitus. AB - The pathogenesis of diabetic vascular disease is not completely known. Many authors have suggested that hemorheological disturbance is an important factor in the development of vascular complication. The hypercoagulable state also suggested to cause this complication. In order to assess the role of blood coagulation in diabetic patients, we investigated hypercoagulation in diabetic patients and its relation with duration of the disease, smoking habits, blood pressure, blood glucose, diabetic retinopathy, diabetic ulcers and patient treatment. A case control study was done to evaluate these factors in 60 diabetic patients in out-and in-patient clinics of the Department of Internal Medicine, General Hospital Dr M Jamil Padang, during December 1990-March 1991. The average age was 51.55 years, average duration of the disease 5, 8 years. Fibrinogen levels is higher in diabetic patient (mean +/- SD = 442.42 +/- 86.79 mg/dl), compared to normal person (mean +/- SD = 349.2 +/- 35.26 mg/dl), PT is shorter (mean +/- SD = 10.1 +/- 1.31 sec), compared to normal person (mean +/- SD = 11.04 +/- 0.93 sec), APTT is also shorter (mean +/- SD = 29.2 +/- 3.69 sec), compared to normal person (mean +/- SD = 32.16 +/- 3.77 sec). There was a significantly high fibrinogen and short PT and APTT in diabetic patients, especially those who suffered from diabetes for a long time and followed by chronic complications. PMID- 7886594 TI - Congenital afibrinogenemia in Hasan Sadikin Hospital. AB - A case of a 24-year-old male with congenital afibrinogenemia has been discussed. The diagnosis was made based upon history, physical examination, umbilical cord bleeding, bleeding history and similar cases were found being the patient's grandfather and brother. Laboratory tests supported the diagnosis with a prolonged bleeding time, prothrombin time (PT), undetected partial thromboplastin time (PTT), flat line on thromboelastogram, and undetected fibrinogen (less than 78 mg/dl), with substitution test which showed fibrinogen deficiency. PMID- 7886596 TI - The management of hemophilia in Jakarta. PMID- 7886595 TI - Hemophiliacs--a picture from a developing country: Karnataka, a south Indian state. AB - Forty cases of hereditary bleeding disorders, who are the members of Karnataka Hemophilia Society (a State Chapter of the Hemophilia Federation of India) were studied to learn their problems. Twenty-four cases were thoroughly investigated including factor assay and in 16 cases the diagnosis was based on classical clinical presentation and pattern of inheritance. There were 16 cases of hemophilia A, 3 cases of hemophilia B, 2 cases of von Willebrand's disease, 1 case of factor XIII deficiency and 2 cases of hereditary afibrinogenemia. The age group varied from 3 months to 36 years; 39 were male. The age of onset of symptoms, type of bleeding, type of joints involved, disabilities experienced by these patients, severity of the disorder, presence of antibodies to factor, presence of HBsAg and HIV, the availability of treatment for these patients, treatment received and the financial burden faced by these patients were studied. Thirty-three cases (82.5%) had joint bleeds, 60% of the patients experienced various type of disabilities, 11 (27.5%) had epistaxis, 10 (25%) had GI bleeds, 5 (12.5%) had dental bleeding, 8 (20%) had haematomas, 3 (7.5%) had umbilical stump bleeds and 19 cases (47.5%) had previous blood transfusions. PMID- 7886597 TI - Anti-HIV, anti-HCV, syphilis, HBsAg serologic tests among high-risk groups and blood donors in Yogyakarta, Indonesia. AB - This report showed anti-HIV among high-risk groups and blood donors in Yogyakarta were still negative. The frequency of HBsAg among blood donor was 2% (RPHA), 3% (ELISA) positive. Test for syphilis gave 0.3% positive. PMID- 7886598 TI - Hepatitis C among blood donors in Jakarta. AB - One type of non-A non-B hepatitis (NANBH) is caused by hepatitis C virus (HCV), and is mostly transmitted through blood transfusion or its components. The prevalence of NANBH among post transfusion hepatitis (PTH) in Western countries is around 90-95%. After Chiron had identified the viral protein which caused parenteral NANBH or HCV, it became possible to detect the antibody for HCV as a sign of its transmission. In Indonesia, the usage of blood and its components gradually increased every year. Since 1985, all blood components from the Indonesian Red Cross were screened against hepatitis B virus (HBV), and it was found that most of the post-transfusion hepatitis were caused by HCV. In this study, the prevalence of the HCV antibody in blood donors was 3 out of 193 (1.6%) using the ELISA method (Ortho). PMID- 7886599 TI - A clinico-hematological profile of hemolytic-uremic syndrome. AB - Hemolytic uremic syndrome (HUS) is defined as microangiopathic hemolytic anemia, thrombocytopenia and uremia. It is an important cause of acute renal failure (ARF) in children all over the world. The present study was carried out to assess the incidence, clinical presentation, hematological and biochemical profile of children presenting with HUS from 1987 to 1990. Out of the 100 cases who presented with ARF 22 had HUS. A majority of these children were males below 1 year of age, and had a prodromal phase of mainly gastrointestinal manifestations lasting for about a week. Anemia was a constant feature followed by bleeding diathesis, mainly melena and purpura. Neurological manifestations included altered sensorium, irritability, coma, hypertensive encephalopathy and convulsions. Renal problems mainly included oliguria, hypertension, hematuria and edema. Investigations revealed thrombocytopenia and microangiopathic hemolytic anemia in all cases. Evidence of disseminated intravascular coagulation (DIC) was observed in 3 cases as decreased fibrinogen levels, increased fibrinogen degradation products and deranged clotting studies. Blood biochemistry revealed azotemia in all cases, hyponatremia in 5 cases, hypernatremia in 3 cases and hyperkalemia in 12 cases. Stool culture showed the presence of Shigella in 8, E. coli in 6 and Klebsiella in 4 cases. Out of 22 cases of HUS, 15 were treated conservatively; of these 2 died. Both of these deaths were due to DIC 7 children were put on peritoneal dialysis; only 1 child died in this group. Factors affecting the outcome were duration of oliguria, levels of blood urea and presence of encephalopathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886600 TI - Hemophilia: the changing role of the orthopedic surgeon in the era of HIV infection. AB - HIV infection and AIDS have posed additional challenges to the orthopedic surgeon and they are discussed in this paper. The acute hemarthrosis. 1. Undertreatment has resulted in further joint degeneration 2. A hemarthrosis with an unusual pain pattern or an elevated temperature may be a pyarthrosis and aspiration and culture are necessary for diagnosis. This complication was very rare prior to HIV infection. Synovitis. 1. In the past we suggested factor replacement and steroids as the primary method of treatment. The use of steroids may be contraindicated in the HIV positive patient. 2. Radioactive synovectomy should be considered in the immune compromised patient. 3. The risks to the surgical team of arthroscopic synovectomy are discussed. Advanced arthropathy. 1. A late infection rate of 10.4% in HIV positive patients with total knee replacements has changed the indications for this procedure. 2. Lesser procedures such as arthrotomy and osteotomy should be considered. Pseudotumor. 1. The indications for pseudotumor surgery must include an evaluation of the risk-benefit ratio in the patient with HIV infection. 2. The orthopedic surgeon must accept the challenge of stimulating and training his students and residents in the principles of orthopedic care of the person with hemophilia. PMID- 7886601 TI - Comprehensive care of hemophilia: role of the dentist. AB - To provide effective dental treatments for patients with bleeding disorders, it is necessary to educate them about the existence and recognition of dental diseases and the effective way in dental preventive care, such as proper brushing, nutrition, good care for dental hygiene. Good and close cooperation among patients, patient's family, physicians, dentists and other medical personnel will provide successful management. Patients with bleeding disorders should have routine preventive dental treatment in the hospital or clinic on a regular basis. Most patients should be on a six months recall program. Some should be seen more frequently, according to their dental health. PMID- 7886602 TI - Detection of carriers and prenatal diagnosis of bleeding disorders. AB - Carrier detection and prenatal diagnosis in the three commonest bleeding disorders (hemophilia A and B and von Wilebrands disease) can be performed either phenotypically or genotypically. Phenotypic analysis for carrier detection results only in a probabilistic assessment whereas DNA analysis, either by direct defect detection or by DNA polymorphism based gene tracking, can result in an accuracy of effectively 100%. Direct defect detection is the method of choice but can be technically demanding. Polymorphism analysis is much simpler and is now being used in family studies world wide. PMID- 7886603 TI - Comprehensive hemophilia care and home factor infusions. PMID- 7886604 TI - Trend study on HBsAg prevalence in Thai voluntary blood donors. AB - In 1973, the prevalence of HBsAg positive individuals was 9.33% in new army recruit blood donors and 8.28% in the general population (CIEP). The hepatitis B vaccine, which was introduced to use in Thailand in 1985, seems to be effective in reducing the prevalence of hepatitis B carriers year after year. In 1991, the prevalence of HBsAg in new blood donors (74,530) was 6.45% (RPHA). However, it was still relatively high at 8.38% in new army recruit blood donors, while in the general population it had decreased to 6.75%. The data suggested that carriers were more likely to be found in new army recruit blood donors, because most of them are from lower socioeconomic groups, less well educated, from rural areas and sexually active. Therefore, the immunization against hepatitis B must be considered for this high risk group in order to reduce the number of hepatitis B carriers. PMID- 7886605 TI - Developing and maintaining of hemophilia programs in developing countries. AB - There are elements key to the success of developing and maintaining hemophilia programs in developing countries. Health care providers who are dedicated champions of hemophilia care are essential. Their training through the WFH International Hemophilia Training Centers brings them in contact with modern comprehensive care as well as establishes collegial linkages with treaters in developed centers. Affordable, safe, viral free coagulation products are essential for an effective hemophilia program. Developing essential for an effective hemophilia program. Developing countries may have to use intermediate purity products because of economic considerations, but technologies must be used which reduce the risk of viral contamination. Successful programs also result from linking to hemophilia programs with national health care initiatives. Hemophilia health care must be recognized as a priority within the developing country's health care system. PMID- 7886606 TI - Development and maintenance of hemophilia programs in developing countries. AB - A hemophilia care program should be able to provide comprehensive medical care to the person with hemophilia and fundamental to the provision of such care is the ability to provide adequate hemostatic support to the hemophilic person with his congenital hemorrhagic diathesis. Development of such a program depends on the presence and commitment of key medical and paramedical personnel and on the recognition of the fact that hemophilia exists in a particular country or community. Support programs ultimately require government assistance for provision of diagnostic facilities and most importantly for a blood transfusion service where production of blood and preparation of blood components for therapy can be undertaken. To maintain a hemophilia care program there should be viability and education of staff and an undertaking by governments for the provision of an on-going infrastructural financial support. As patients mature, new problems will arise, some of which may be a direct complication of hemophilia. Involved medical staff require support and continuing education to continue to provide essential support to the people with hemophilia. Finally, it must be stressed that hemophilia care does not stand alone but must be incorporated into the network of provision of health care based on an efficient and viable blood transfusion service. PMID- 7886607 TI - Vitamin K deficiency. AB - Vitamin K (phylloquinone, K1; menaquinone, K2) functions as an essential cofactor for the synthesis of the coagulation protein factors II, VII, IX, X and protein C and S by promoting a unique post-translational modification of specific glutamic acid residues to gamma-carboxylglutamic acid, thus mediating calcium binding to phospholipid surfaces. Vitamin K deficiency results in a depletion of liver stores of phylloquinone, decreased plasma levels of vitamin K1, increased levels of K1 epoxide, appearance of noncarboxylated protein (PIVKA), decreased levels of functioning vitamin K-dependent clotting factors and prolongation of the APTT, PT and thrombotest. When the progression of deficiency leads to abnormal clotting tests a generalized bleeding tendency occurs. Noncarboxylated prothrombin (PIVKA II) determinations are a sensitive indicator of vitamin K deficiency. Although Vitamin K deficiency can occur at any age (warfarin, fasting, antibiotic therapy, malabsorption syndromes) the major public health problem is related to prevention of early, classic and late hemorrhagic disease of the newborn (HDN). A single dose of oral or parenteral vitamin K prevents classic HDN but the most effective way to prevent early HDN is by giving large doses to the mother prior to delivery (2 weeks). Late HDN in breastfed infant occurs with a prevalence of about 20 per 100,000 live births when no neonatal prophylaxis is given. Parenteral (1 mg) K1 prevents late HDN and single or repeated doses of oral vitamin K reduces the incidence but does not eliminate all late HDN. The optimal (cost, feasibility, effective) mode of neonatal prophylaxis remains to be determined. PMID- 7886608 TI - Development and maintenance of hemophilia care program in Korea. PMID- 7886609 TI - Developing and maintaining the hemophilia program in Thailand. AB - Developing of the hemophilia program in Thailand during 1978-1990 has been achieved step by step as follow: 1. In 1978, organizing a series of scientific conferences to motivate and recruit expert teams and to have support from the health authority. 2. In 1978, a national survey of hemophilia which showed an incidence of 1:13,000 of population. 3. Training medical and paramedical personnel during 1973-1992. 4. In 1980, establishment of the National Hemophilia Society. 5. Improvement of blood bank and blood product supported by National Blood Center, Red Cross Society during 1960-1992. 6. In 1981, submitting hemophilia program to the 5th National Health Developmental Plan for 1982-1986. 7. Establishment of a nationwide hemophilia care program by integration with the national health care system. 8. In 1979, starting a home care program and initiation of comprehensive hemophilia care. 9. In 1982, promotion of comprehensive hemophilia care surgical orthopedic correction. 10. Promotion of local manufacture of equipment, reagents, therapeutic material and modification of technology. 11. In 1987, carrier detection. 12. In 1990, laboratory set up for prenatal diagnosis. The future plan is described for the years 1992-2000. PMID- 7886610 TI - Developing hemophilia services in India. AB - With a population of 853 million there should be 51,204 patients with hemophilia A in India assuming a prevalence of 6/100,000 population. With the current birth rate of 32/1000, 1,300 new patients with hemophilia A will be born each year. Hospital based data suggests that hemophiliacs in India suffer from preventable morbidity because doctors do not know enough about the disease and its management, because laboratory diagnostic facilities are inadequate and because there is not enough therapeutic material or even if it is available the patients do not have the resources to purchase it. This article reviews the current status of hemophilia in India and suggests measures to improve hemophilia services within the health care infrastructure available in the country. PMID- 7886611 TI - The response to treatment in chronic idiopathic thrombocytopenic purpura (ITP). AB - Immune thrombocytopenic purpura (ITP) is a relatively common illness. The initial recommended therapy is glucocorticoids, however due to low response rate and high rate of relapses, the second preferred line of therapy is splenectomy. About 60% of the patients respond to this therapy. A retrospective study performed in Israel in 226 children and 446 adults with ITP has evaluated the response to steroids and splenectomy. The response rates were similar to reported studies and no significant differences were observed between children and adults. The possibilities of treating patients who fail splenectomy and exhibit refractory disease are summarized. PMID- 7886612 TI - Therapy of chronic idiopathic thrombocytopenic purpura in adults: experiences from Thailand. AB - Results of different types of treatment in 416 adults with chronic idiopathic thrombocytopenic purpura (ITP) were analyzed. Of 368 patients treated with corticosteroids, 278 (77%) achieved complete response (CR ie, normalization of platelet count). However, only 18% of patients had continued complete response (CCR). Results of splenectomy was analyzed in 126 patients, 49% of them achieved CCR and 76% of them had beneficial effects from the operation. Emergency splenectomy was a life saving procedure in 8 of 11 patients with life-threatening hemorrhage. Vinca alkaloids gave a 50% transient CR. Immunosuppressive agents (cyclophosphamide, azathioprine) resulted in only 11% CCR. PMID- 7886613 TI - Problems associated with compatibility testing for patients with autoimmune hemolytic anemia. AB - Two major areas where problems are encountered when performing compatibility testing for AIHA patients are ABO/Rh typing and crossmatching blood for transfusion. ABO/Rh typing is usually not a problem with warm type AIHA (WAIHA), but sometimes false positive Rh typing results may occur with reagents containing potentiators (eg, albumin). Approaches to overcoming this problem include using reagents not having potentiators, or removing IgG from RBCs (eg, using chloroquine) before typing. Major problems are encountered when typing patients with cold agglutinin syndrome (CAS). These can usually be resolved by using RBCs that have been washed at 37 degrees C, and testing the serum with A, B and O cells at 37 degrees C using the "prewarm" technique. When crossmatching blood for patients with CAS, all tests should be carried out with saline or LISS-suspende RBCs, strictly at 37 degrees C; albumin or enzyme techniques should be avoided. If sera from WAIHA are reacting with all RBCs, the presence of underlying alloantibodies must be excluded by performing absorption studies with with autologous, or homologous RBCs. If alloantibodies are present, they should be identified, and "antigen negative" blood crossmatched. If alloantibodies are not present, and if time allows, the less important autoantibody specificity may be studies. If specificity is shown (eg, auto anti-e) and appropriate donors (eg, e negative) are available, with relative ease, then it is preferable to use this blood. If the appropriate compatible donors are rare [eg, Rhnull, LW-, U-, Kp (b )], they should not be used for AIHA but should be reserved for patients with alloantibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886614 TI - Abnormal hemostasis in dengue hemorrhagic fever. AB - Abstract. Abnormal hemostasis in dengue hemorrhagic fever includes:- 1. Vasculopathy which occurs during the early febrile to pre-shock and shock phase. The evidences support are: 1.1 Increased anaphylatoxin, released by complement activation causing leakage of intravascular fluid in to serous space. 1.2 Positive tourniquet test, some of which occur preceeding thrombocytopenia in the acute phase of DHF. 1.3 Excessive increased in PGI2 which is the most potent vasodilator and platelet aggregation inhibitor. 2. Platelets: 2.1 Thrombocytopenia due to 2.1.1 The bone marrow hypocellularity with increased in all forms of megakaryocytes but the vacuolated and disintegrated ones. 2.1.2 Destruction by the liver and spleen. 2.1.3 Immune-mediated injury as demonstration of dengue antibody complexes on the platelet surface. 2.1.4 The in vitro spontaneous aggregation to vascular endothelial cell pre-infected by dengue virus inducing platelet aggregation, causing lysis and platelet destruction. 2.2 Dysfunction shown by 2.2.1 Increased release of betathromboglobulin (BTG), PF4 and PGI2. 2.2.2 In vitro hypoaggregation stimulated by ADP and defect in ADP releasing ability. 3. Coagulopathy including: 3.1 Prothrombin complex deficiency due to liver damage. 3.2 Consumptive coagulopathy due to the activation by mononuclear phagocytes, PF3 released from platelet aggregation. DIC is seen in prolonged shock cases of DSS. PMID- 7886615 TI - Hemostatic alterations in malaria. PMID- 7886616 TI - A chronic hypercoagulable state and life-long platelet activation in beta thalassemia major. AB - Increased frequency of thromboembolic events has been recently observed in patients with thalassemia major (TM), causing hypoxemia and cor pulmonale. Autopsy findings demonstrated "old" and recent pulmonary and renal infarcts as well as premature atherosclerosis. Studies to determine hypercoagulability showed: impaired platelet aggregation, increased circulating platelet aggregates, shortened platelet survival, enhanced excretion of urinary metabolites of thromboxane A2 (TXA2) and prostacyclin and decreased plasma levels of Protein C, Protein S or anti-thrombin III. Erythrocytes from TM patients enhanced thrombin formation in a "prothrombinase" assay (using a chromogenic substrate). Chronic anti-thrombotic therapy may be indicated in thalassemic patients to prevent the cardiac and pulmonary complications. PMID- 7886617 TI - High transfusion in children with beta-thalassemia/Hb E: clinical and laboratory assessment of 18 cases. AB - Between 1990-1992, 18 patients with beta-thalassemia/Hb E age between 2-13 years (mean 7.4 +/- 3 years) were examined. Three patients were splenectomized and the rest were nonsplenectomized. They were divided into 3 groups. Group A:5 nonsplenectomized and 3 splenectomized patients had high transfusion rates with subcutaneous desferrioxamine injections. Five patients in group B received only high transfusion whereas in 5 patients in group C the levels pretransfusion Hb were maintained between 6-7 g/dl. The mean blood consumption in the nonsplenectomized groups were 220 +/- 25.3, 221 +/- 59 and 175.4 +/- 45.4 ml/kg/year in groups A, B and C, respectively. In group A, the mean blood requirement was 40% higher in the nonsplenectomized group. In the high transfusion regimen the spleen size did not increase and serum aspartate aminotransferase showed a striking fall in the majority of cases. The absolute increases in serum ferritin were 843.2 +/- 395, 861 +/- 252 and 1,262 +/- 440 ng/ml in groups A, B and C, respectively. These data demonstrated that high transfusion with desferrioxamine injection could improve the clinical well being of the patients. PMID- 7886618 TI - Dental enamel in relation to ionized calcium and parathyroid hormone. Studies of human primary teeth and rat maxillary incisors. AB - The aims of this thesis were to evaluate the role of lowered calcium values in blood on enamel formation and mineralization, and further to analyze whether the calcium regulating parathyroid hormone (PTH) would have any effects on the forming and mineralizing enamel. DENTAL ENAMEL AND IONIZED CALCIUM: Human primary teeth from two groups of infants were clinically and histologically examined. One group (n = 25) was born with optimal perinatal conditions. The infants had low, but not hypocalcemic values on day 1 when compared with days 3 and 5 postpartum. The second group of infants (n = 11) was subjected to blood exchange transfusion on the first few days postpartum. All infants developed very low values of blood ionized calcium due to the treatment, and the infants had a mean of three hypocalcemic days. Enamel aberrations were seen in both groups, but only four infants had multiple enamel aberrations located at levels corresponding to the enamel development at the time of the birth. Low values of blood ionized calcium alone were not associated with enamel aberrations, as the aberrations were only seen in infants subjected to more than three blood exchange transfusions. The neonatal line was present in all teeth investigated, thin lines dominated, and the widths were not dependent on the levels of blood ionized calcium during the first few days after birth. Rats were also used to investigate whether the maxillary incisor enamel would be affected during a diet-induced hypocalcemic state. Of ten experimental rats, nine had normal enamel, indicating that hypocalcemia in rats does not generally affect the enamel. DENTAL ENAMEL AND PARATHYROID HORMONE: Rats was used in a study where they were subjected to daily injections of PTH. Three different doses were used and the experimental periods were 7 and 14 days. In a pilot part, enamel aberrations were seen but not in the main study performed later. The main difference in experimental design between the pilot and the main part of the study was the use of hard tissue marker, oxytetracycline, at start of the pilot part. For this reason, a separate study was performed to evaluate the use of oxytetracycline in hard tissue research. The results clearly demonstrated that oxytetracycline itself induces enamel aberrations and so it was not used in the main study of parathyroid hormone. As no enamel aberrations were seen in the main part, it was concluded that the doses of PTH used do not seem to affect enamel formation and mineralization. PMID- 7886619 TI - Differential influence of electrical blocking agents on embryonic acetylcholine receptor mRNA levels in long-term cultures of aneural mammalian myotubes. AB - The influence of spontaneous muscle activity on acetylcholine receptor (AChR) expression was examined by exposing long-term cultures of mammalian myotubes to two pharmacological agents that have similar effects on the rate of spontaneous contractile activity but pharmacologically distinct actions on voltage gated Na+ channels. Previous studies by other investigators have shown that tetrodotoxin upregulates and that veratridine downregulates surface AChR expression in short term mammalian muscle cultures. In order to determine whether these drugs have disparate actions on AChR mRNA levels, myotubes were exposed to either tetrodotoxin or veratridine for a period of 10 days, and measurements of the relative levels of embryonic AChR subunit mRNAs (alpha, beta, gamma, delta) were obtained during and following the period of drug exposure. Veratridine produced a substantial decrease (between 33% and 50% reduction), while tetrodotoxin produced a relatively small increase (between 17% and 23%), in each of the AChR subunit mRNAs after 6 days of drug exposure. At 23 days in culture, spontaneously active myotubes exhibited a decrease in the relative levels of each of the AChR subunit mRNAs. Myotubes previously exposed to either veratridine or tetrodotoxin exhibited elevated levels of beta, gamma, and delta AChR subunit mRNAs 6 days after cessation of drug treatment, thus suggesting that a period of muscle inactivity can induce sustained influences on some AChR mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886620 TI - Differential effect of MK 801 and scopolamine on c-fos expression induced by L dopa in the striatum of 6-hydroxydopamine lesioned rats. AB - In rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigro striatal pathway, striatal D1-receptor-stimulated c-fos expression and turning behavior are positively modulated by D2 receptor stimulation and by blockade of N methyl-D-aspartate (NMDA) or muscarinic receptors. Combined D1/D2 receptor stimulation by L-dopa activates c-fos in a manner not additive with muscarinic receptor blockade by scopolamine. On the other hand, blockade of NMDA receptors by MK 801 reduced c-fos expression induced by L-dopa while, depending on the dose of L-dopa, differentially affecting contralateral turning behavior. The results are interpreted to suggest that D2 receptor stimulation amplifies D1-receptor mediated c-fos expression by two mechanisms differentially related to muscarinic and NMDA receptors. PMID- 7886621 TI - In vivo biogenic amine efflux in medial prefrontal cortex with imipramine, fluoxetine, and fluvoxamine. AB - In vivo brain microdialysis was used to determine the effects of the standard tricyclic antidepressant imipramine and the two selective serotonin reuptake inhibitors (SSRIs) antidepressants, fluoxetine and fluvoxamine, on extracellular levels of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in rat medial prefrontal cortex. When given intraperitoneally (IP), imipramine increased NE in the microdialysis perfusate, and elevated DA and 5-HT to a lesser extent. Similar dose-dependent increases in DA and 5-HT were detected after IP fluoxetine, although NE was less affected. In contrast, IP fluvoxamine produced no change in basal NE nor DA, although a large increase in 5-HT occurred at an intermediate dose. When administered directly into cortex, all three antidepressants increased 5-HT by the same amount in a dose-dependent fashion. Intracortical imipramine and fluoxetine increased NE, and fluoxetine and fluvoxamine both increased DA, with fluoxetine doing so at a lower concentration. These data suggest that the SSRIs are not entirely selective for serotonin in vivo. PMID- 7886622 TI - Further characteristics of long-term potentiation in piriform cortex. AB - Mechanisms for the induction and expression of long-term potentiation (LTP) were studied in slices of piriform cortex. Cooperativity among afferent inputs as a controlling factor for induction of LTP was tested by pairing stimulation of one input that normally does not induce LTP with stimulation of another input. Combined stimulation, given either to two weak inputs with simultaneous bursts or by pairing single pulses with bursts, did effectively induce LTP. Tests for expression of LTP by NMDA vs. non-NMDA receptors indicated that non-NMDA receptor mediated responses expressed much greater LTP than NMDA receptor-mediated responses. Ratios for paired-pulse facilitation and depression were not altered after induction of LTP. These characteristics are comparable to those exhibited by synapses in the CA1 field of hippocampus. PMID- 7886623 TI - Anesthetics block morphine-induced increases in serotonin release in rat CNS. AB - The effect of morphine on serotonin (5-HT) was examined by microdialysis in unanesthetized and anesthetized rats. In unanesthetized rats, morphine (10 mg/kg, s.c.) produced increases in extracellular 5-HT in nucleus accumbens (n. accumbens) and dorsal raphe nucleus (DRN), but not in the dorsal hippocampus. Similarly, extracellular 5-HT in the n. accumbens, but not the dorsal hippocampus, was increased after morphine (1 mM) was infused for 60 min by reverse dialysis into the DRN. Chloral hydrate, pentobarbital, and ketamine anesthesia had different effects on 5-HT in the n. accumbens. Chloral hydrate induced a transient increase and ketamine a sustained increase in extracellular 5 HT. Pentobarbital caused a sustained decrease. The effects of systemic and intraraphe administration of morphine were abolished by all three anesthetics. Infusion of muscimol, a GABAA receptor agonist, into the DRN also induced a decrease in 5-HT and abolished the effects of morphine on 5-HT in the DRN and n. accumbens. These results are consistent with other evidence suggesting that morphine-induced increases in monoamine neurotransmission are a disinhibitory effect resulting from opioid-mediated inhibition of GABA release. More conclusively, it is apparent that anesthetized animals are inappropriate for testing the effect of morphine on 5-HT neurotransmission. PMID- 7886624 TI - Alterations in TRH receptors in temporal lobe of schizophrenics: a quantitative autoradiographic study. AB - We utilized quantitative autoradiography to determine the distribution of receptors for thyrotropin-releasing hormone (TRH) throughout the human temporal lobe and to examine the distribution of these receptors in discrete subregions of the temporal lobe from patients diagnosed premortem with schizophrenia. When compared to non-neurologic controls, schizophrenic patients demonstrated an increase of 51% in the concentration of TRH receptors in the molecular layer of the dentate gyrus. Within nuclei of the schizophrenic amygdala, marked decreases were found in the central (44%), medial (38%), cortical (36%), accessory cortical (52%), lateral (54%), and medial basal (22%) nuclei. We also examined postmortem brain samples from patients with Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease for alterations in the distribution of TRH receptors. No significant differences from non-neuropsychiatric controls were noted within the hippocampus in any of these disease states; however, slight alterations were noted in the central and medial basal amygdala in Huntington's disease and in the cortical amygdala in Alzheimer's disease. These disease specific findings suggest that TRH may play a role in the neurochemical dysfunction of schizophrenia. PMID- 7886625 TI - Quantal analysis of presynaptic inhibition, low [Ca2+]0, and high pressure interactions at crustacean excitatory synapses. AB - The cellular mechanisms underlying the effects of high pressure, GABAergic presynaptic inhibition, and low [Ca2+]0 on glutamatergic excitatory synaptic transmission were studied in the opener muscle of the lobster walking leg. Excitatory postsynaptic currents (EPSCs) were recorded with or without prior stimulation of the inhibitor using a loose macropatch clamp technique at atmospheric pressure and at 6.9 MPA helium pressure. High pressure reduced the mean EPSC amplitude and variance, decreased the quantal content (m), but did not affect the quantum current (q). Pressure shifted the median of the amplitude histogram to the left by 1-2 q. Under normal pressure conditions, presynaptic inhibition and low [Ca2+]0 induced similar effects. However, quantal analysis using a binomial frequency distribution model revealed that high pressure and low [Ca2+]0 diminished n (available active zones) and slightly increased p (probability of release), but presynaptic inhibition reduced p and slightly increased n. At high pressure, presynaptic inhibition was reduced, at which time the major contributor to the inhibitory process appeared to be reduction in n and not p. The similarity of the alterations in quantal parameters of release at high pressure, low [Ca2+]0, and in some conditions of presynaptic inhibition is consistent with the hypothesis that pressure reduces Ca2+ inflow into the presynaptic nerve terminals to affect the Ca(2+)-dependent quantal release parameters n and p. PMID- 7886626 TI - Glutamatergic antagonists attenuate ability of dopamine uptake blockers to increase extracellular levels of dopamine: implications for tonic influence of glutamate on dopamine release. AB - Previous in vivo studies reporting a dose-dependent increase in extracellular dopamine (DA) levels by excitatory amino acid (EAA) antagonists have been interpreted to indicate a lack of tonic excitatory effect exerted by these amino acids on striatal DA release. Alternatively, a tonic excitatory influence on DA release may affect a small fraction of DA terminals, so that blockade of this effect does not make a great enough contribution to the extracellular fluid to be detected by microdialysis. To examine this possibility, the effect of EAA antagonists was assessed by microdialysis in the presence of DA uptake blockers. It was found that in the presence of nomifensine or cocaine, antagonists of either NMDA or AMPA/kainate receptors decreased extracellular DA levels in the striatum. These data suggest that EAAs may exert a tonic facilitatory influence on striatal DA release and/or that endogenous EAAs may potentiate the action of DA uptake blockers through mechanisms that are mediated by EAA receptors. PMID- 7886627 TI - NMDA receptors mediate amphetamine-induced upregulation of zif/268 and preprodynorphin mRNA expression in rat striatum. AB - The role of N-methyl-D-aspartate (NMDA) excitatory amino acid receptors in D amphetamine (AMPH)-induced behavioral changes and increased expression of the nuclear transcription factors, c-fos and zif/268, and preprodynorphin (PPD) mRNA in various regions of rat forebrain was investigated with quantitative in situ hybridization histochemistry. Three hours after a single injection of AMPH (5 mg/kg, i.p.), the mRNA expression of zif/268, but not c-fos, in dorsal striatum (caudate nucleus) and cerebral cortex (sensorimotor cortex), and PPD mRNA in dorsal striatum, was upregulated. Pretreatment of rats with MK-801 (0.5 mg/kg, i.p.) attenuated AMPH-induced striatal and cortical expression of zif/268 mRNA and striatal expression of PPD mRNA, without affecting the behavioral alterations induced by AMPH. A similar, dose-dependent suppression of AMPH-induced zif/268 and PPD mRNA in striatum and cortex was also revealed after systemic administration of (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) at doses of 5 and 10 mg/kg. CPP, only at the higher dose, slightly attenuated behavioral activity induced by AMPH. MK-801 and CPP (at higher dose) alone suppressed basal (constitutive) zif/268 mRNA levels in both striatum and cortex regions. No significant effect of either antagonist was found on constitutive expression of striatal PPD mRNA. These studies indicate that NMDA receptors mediate, at least in part, activation of zif/268 and PPD gene expression in striatum and sensorimotor cortex by a single injection of AMPH. Furthermore, NMDA receptor-mediated gene regulation more likely is involved in long-term neuronal plasticity to drug exposure than in acute drug effects since NMDA receptor antagonists had little or no effect on the acute behavioral actions of AMPH. PMID- 7886629 TI - In vivo binding of [123I]4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)- p iodobenzamido-]ethyl-piperazine, p-MPPI, to 5-HT1A receptors in rat brain. AB - The in vivo regional distribution and pharmacological profile of a novel iodinated phenylpiperazine derivative, [123I]p-MPPI (4-(2'-methoxy-)phenyl-1-[2' (N-2"pyridinyl)-p-iodobenzamido-]ethy l- piperazine), in the rat brain were evaluated for use as a potential in vivo imaging agent for 5-HT1A receptors. The new ligand penetrated the blood-brain barrier quickly and efficiently, with 1.2% of the injected dose found in the whole brain at 2 min post i.v. injection. The rate of radioactivity washout was slowest from the hippocampal region, followed by the hypothalamus, cortex, striatum, and cerebellum. The maximum ratio of hippocampus/cerebellum was 3.3 at 30 min postinjection. The specific binding of the radioligand in the hippocampal region, an area rich in 5-HT1A receptor density, was blocked by pretreatment with a dose of (+/-) 8-OH-DPAT (2 mg/kg, i.v.) or WAY 100635 (1 mg/kg, i.v.), whereas the regional distribution of [123I]p MPPI was unaffected by pretreatment with non-5-HT1A agents such as ketanserin or haloperidol. Ex vivo autoradiographic studies further confirmed that the specific binding of [125I]p-MPPI is associated with 5-HT1A receptor sites. These results indicate that [123I]p-MPPI may be a useful candidate for noninvasive single photon emission computed tomography (SPECT) imaging of 5-HT1A receptor sites in the living human brain. PMID- 7886628 TI - Interleukin-1 alpha induces corticotropin-releasing factor secretion and synthesis from NPLC-KC cells through various second messenger pathways. AB - Interleukin-1 (IL1) is a key messenger implicated in endocrine and immune systems that interact to mediate the stress response. Corticotropin-releasing factor (CRF) secretion and synthesis in the NPLC-KC human hepatoma cell line has been shown to respond to IL1 stimulation. We have studied how various inhibitors of second messenger pathways alter this IL1 effect. NPLC-KC cells were grown in six well Costar plates and treated for 12 or 24 h with or without 500 pM IL1 (alpha form) in the presence of various inhibitors of second messenger pathways. Inhibitors included the protein kinase C (PKC) inhibitor, H-7; the protein kinase A inhibitor, IP20; or the cyclooxygenase inhibitor indomethacin (IND). Both cell extracts and secretion media were assayed for CRF-like immunoreactivity by radioimmunoassay. IP20, H-7, and IND all reduced basal CRF secretion at 24 h but not at 12 h. No effects were seen on basal CRF synthesis with these inhibitors. The three inhibitors also reduced IL1 effects on CRF secretion at 12 and 24 h. The reduction seen with all three inhibitors was statistically significant (P < 0.05) at 12 h. Although a reduction was seen with all three inhibitors at 24 h, a statistically significant reduction (P < 0.05) was demonstrable only for H-7. IL1 stimulated CRF synthesis in the NPLC-KC cells appears to only involve PKC pathways. Only the PKC inhibitor H-7 reduced the augmentation that IL1 produces on CRF synthesis. This effect was statistically significant at 12 and 24 h (P < 0.05). PMID- 7886630 TI - Illness, the mind, and the body: cancer and immunology: an introduction. AB - From the sixties on it has become clear how the human physical condition could be influenced by human behavior. Although hypothesis were lacking to understand these connections, nursing research especially proved how systematically introduced patient behavior during illness and hospitalization could induce better recovery results and better prognosis for the patient. Information and attitude proved to be crucial elements in these processes of improved patient expectations. It took less than two decades to get to the insights we have in 1994. Recent research shows the interlocking mechanisms of nervous and endocrine systems with the immune system as significantly being influenced by behavior and especially psychic and or psychosocial stress. This special issue of Theoretical Medicine briefly describes the historical development with contributions on the most recent state of the scientific art. These developments are emphasized by discussion on the clinical reality of the (breast) cancer patient and recent findings on the complexity of the prevalence of cancer in epidemiology. An attempt is made to consider practical consequences of the actual knowledge if applied to patient care. PMID- 7886631 TI - The trauma triangle. AB - Recent research supports the hypothesis that more active engagement of the patient in occurring illnesses improves quality of life and probably even life expectancy. In this study experience and theoretical knowledge from psychotherapy is transplanted to clinical practice in order to improve the physician's engagement in the patient-disease relationship. By defining severe and long-term illnesses as a psychotrauma, the transfer of the psychotherapeutical model leads to the creation of a new triangular relationship: patient-illness-doctor. Practical examples are used as illustrations for the conceptual differences between psychotherapy and clinical medicine. Options for dialogue show the difference between adaptation ("learning to live with") and adjustment (active coping strategies and controlling). The hypothesis is that a better dialogue will reduce illness-related stress, giving the patient better and more effective access to personal psychic and physical support systems. PMID- 7886632 TI - Genes and family environment in familial clustering of cancer. AB - Familial clustering of a disease is defined as the occurrence of the disease within some families in excess of what would be expected from the occurrence in the population. It has been demonstrated for several cancer types, ranging from rare cancers as the adenomatosis-coli-associated colon cancer or the Li-Fraumeni syndrome to more common cancers as breast cancer and colon cancer. Familial clustering, however, is merely an epidemiological pattern, and it does not tell whether genetic or environmental causes or both in combination are responsible for the familial clustering. Familial clustering may be due to genetic predisposition to the disease, but exposure to environmental factors--shared by members of some families, but not by members of other families--may also cause familial clustering and hence mimic genetic inheritance in the study of nuclear families. Based on assumptions regarding the individual steps in the biological process starting with exposure to carcinogens and ending with death from disseminated cancer we suggest that genetic and environmental factors may both be involved in most of these steps. The present paper focuses on research methodologies necessary to discriminate between the effect of genes and family environment in the development of cancer. PMID- 7886633 TI - The mind and the immune system. AB - Stress-induced brain-mediated immunoregulation is effected by two pathways: autonomic outflow and (neuro)endocrine outflow. Particular attention is given to the interaction-effects of chronic an acute stress. Recent data have established that cells of the immune system produce neuro-peptides and hormones. In concert with cytokines released by these immune cells the brain can be informed on the nature of ongoing immune activity. The significance of conditioning of immune responses is discussed. PMID- 7886634 TI - The last invasion of human privacy and its psychological consequences on survivors: a critique of the practice of embalming. AB - In spite of the fact that it is required only occasionally for sanitary reasons and not legally mandatory, the practice of embalming is widespread in contemporary American society. This study explores the historical, cultural and psychological factors which gave rise to the practice of embalming and why the practice continues. Two case studies are presented in which delayed grief reactions were present; linkages with embalming are described. It is suggested that the frightening finitude of the self and a fear of death in modern society have led to practices in which the corpse is viewed as looking "natural," thus denying the reality of death. Embalming is seen as the final assault on the self, which can also carry with it problematic psychological consequences for the survivors. PMID- 7886635 TI - A motivational approach to confirmation: an interpretation of dysphagic patients' experiences. AB - In this paper we articulate confirmation and disconfirmation as components in human motivation. We develop a theory of motivation on the basis of a model of human action and we explore aspects of confirmation and disconfirmation in the context of the meeting of dysphagic patients with their physicians. We distinguish four central elements in confirmation and disconfirmation and use these and the relations between them for the purpose of constructing a typology. Finally, on the basis of the results obtained we interpret a small volume of remarks reflecting the meaning field of some dysphagic patients in relation to their physicians. The underlying motive is to develop tools for understanding health care processes. The "SAUC-Confirmation-Model" and the theoretical framework in which it is embedded should be seen from that point of view. PMID- 7886636 TI - Death, medicine & bioethics. AB - The assumptions of philosophy need scrutiny as much the assumptions of medicine do. Scrutiny shows that the philosophical method of bioethics is compromised, for it shares certain fundamental assumptions with medicine itself. To show this requires an unorthodox style of philosophy--a literary one. To show the compromised status of bioethics the paper discusses some seminal utilitarian discussions of the definition of death, of whether it is a bad thing, and of when it ought to occur. PMID- 7886637 TI - Acute severe asthma: oxygen and high dose beta agonist during transfer for all? PMID- 7886638 TI - Endobronchial leiomyoma: a case report. AB - Leiomyoma of the lung is very rare in children. The case history is presented of an 8 year old boy with an endobronchial leiomyoma which caused total atelectasis of the left lung. PMID- 7886639 TI - Bone turnover and inhaled corticosteroids. PMID- 7886640 TI - Malignant pleural effusion. PMID- 7886641 TI - Corynebacterium parvum for malignant pleural effusions. PMID- 7886642 TI - Use of elastin fibre detection in the diagnosis of ventilator associated pneumonia. AB - BACKGROUND: Elastin fibre detection could be a simple and reliable marker of ventilator associated pneumonia. To confirm this, a prospective study was undertaken to evaluate the diagnostic yield of elastin fibre detection in the diagnosis of ventilator associated pneumonia. METHODS: Seventy eight mechanically ventilated patients were evaluated by examining endotracheal aspirates for the presence of elastin fibres. All patients were previously treated with antibiotics. Quantitative bacterial cultures of endotracheal aspirates and protected specimen brush samples were also performed. Patients were classified into three diagnostic categories: group 1, definite pneumonia (n = 25); group 2, probable pneumonia (n = 35); and group 3, controls (n = 18). RESULTS: Patients with definite and probable pneumonia were grouped together. The presence of elastin fibres in endotracheal aspirate samples was more frequent in groups 1 and 2, being found in 19 of the 60 patients compared with five of the control group. Although the presence of elastin fibres had a low sensitivity (32%), it was a reasonably specific marker (72%) of pneumonia. This specificity increased to 86% and 81% respectively when only Gram negative bacilli and Pseudomonas aeruginosa pneumonia were considered. Again, calculated sensitivity was 43% and 44% when analysing cases infected by Gram negative bacilli and Ps aeruginosa, respectively. The negative predictive value of the detection of elastin fibres in pneumonia caused by Ps aeruginosa was 81%. Detection was more frequent with infection by Gram negative bacilli (14/19), particularly with Ps aeruginosa (8/14). By contrast, pneumonia due to Gram positive cocci or non-bacterial agents uncommonly resulted in positive elastin fibre preparations (4/19, 21%). When analysing patients with and without chronic obstructive pulmonary disease, the diagnostic value of elastin fibre detection did not change. CONCLUSIONS: Potassium hydroxide preparation of elastin fibres is a rapid and simple specific marker of ventilator associated pneumonia and may be a useful technique to help diagnose pulmonary infections in mechanically ventilated patients, although this assessment is at present limited to patients without adult respiratory distress syndrome. PMID- 7886643 TI - Doppler assessment of hypoxic pulmonary vasoconstriction and susceptibility to high altitude pulmonary oedema. AB - BACKGROUND: Subjects with previous high altitude pulmonary oedema may have stronger than normal hypoxic pulmonary vasoconstriction. Susceptibility to high altitude pulmonary oedema may be detectable by echo Doppler assessment of the pulmonary vascular reactivity to breathing a hypoxic gas mixture at sea level. METHODS: The study included 20 healthy controls, seven subjects with a previous episode of high altitude pulmonary oedema, and nine who had successfully climbed to altitudes of 6000-8842 m during the 40th anniversary British expedition to Mount Everest. Echo Doppler measurements of pulmonary blood flow acceleration time (AT) and ejection time (ET), and of the peak velocity of the tricuspid regurgitation jet (TR), were obtained under normobaric conditions of normoxia (fraction of inspired oxygen, FIO2, 0.21), of hyperoxia (FIO2 1.0), and of hypoxia (FIO2 0.125). RESULTS: Hypoxia decreased AT/ET by mean (SE) 0.06 (0.01) in the control subjects, by 0.11 (0.01) in those susceptible to high altitude pulmonary oedema, and by 0.02 (0.02) in the successful high altitude climbers. Hypoxia increased TR in the three groups by 0.22 (0.06) (n = 14), 0.56 (0.13) (n = 5), and 0.18 (0.1) (n = 7) m/s, respectively. However, AT/ET and/or TR measurements outside the normal range, defined as mean +/- 2 SD of measurements obtained in the controls under hypoxia, were observed in only two of the subjects susceptible to high altitude pulmonary oedema and in five of the successful high altitude climbers. CONCLUSIONS: Pulmonary vascular reactivity to hypoxia is enhanced in subjects with previous high altitude pulmonary oedema and decreased in successful high altitude climbers. However, echo Doppler estimates of hypoxic pulmonary vaso-constriction at sea level cannot reliably identify subjects susceptible to high altitude pulmonary oedema or successful high altitude climbers from a normal control population. PMID- 7886644 TI - Role of hypoxia on increased blood pressure in patients with obstructive sleep apnoea. AB - BACKGROUND: Cyclical changes in systemic blood pressure occur during apnoeic episodes in patients with obstructive sleep apnoea (OSA). Although several factors including arterial hypoxaemia, intrathoracic pressure changes, and disruption of sleep architecture have been reported to be responsible for these changes in blood pressure, the relative importance of each factor remains unclear. This study assessed the role of hypoxaemia on the increase in blood pressure during apnoeic episodes. METHODS: The blood pressure in apnoeic episodes during sleep and the blood pressure response to isocapnic intermittent hypoxia whilst awake were measured in 10 men with OSA. While asleep the blood pressure was measured non-invasively using a Finapres blood pressure monitor with polysomnography. The response of the blood pressure to hypoxia whilst awake was also measured while the subjects intermittently breathed a hypoxic (5% or 7% oxygen) gas mixture. Each hypoxic gas exposure was continued until a nadir arterial oxygen saturation (nSaO2) of less than 75% was reached, or for a period of 100 seconds. The exposure was repeated five times in succession with five interposed breaths of room air in each run. RESULTS: The mean (SD) increase in blood pressure (delta MBP) during apnoeic episodes was 42.1 (17.3) mm Hg during rapid eye movement (REM) sleep and 31.9 (12.5) mm Hg during non-REM sleep. The delta MBP during apnoeic episodes showed a correlation with the decrease of nSaO2 (delta SaO2) (r2 = 0.30). The change in blood pressure in response to intermittent hypoxia whilst awake was cyclical and qualitatively similar to that during apnoeic episodes. Averaged delta MBP at an SaO2 of 7% and 5% oxygen was 12.6 (5.7) and 13.4 (3.6) mm Hg, respectively, whereas the averaged delta MBP at the same delta SaO2 during apnoeic episodes was 38.4 (15.5) and 45.2 (20.5) mm Hg, respectively. CONCLUSIONS: The blood pressure response to desaturation whilst awake was about one third of that during apnoeic episodes. These results suggest that factors other than hypoxia may play an important part in raising the blood pressure during obstructive sleep apnoea. PMID- 7886645 TI - Opportunities for diagnosing cytomegalovirus in pulmonary infections. PMID- 7886647 TI - Maximal inspiratory pressure: does reproducibility indicate full effort? AB - BACKGROUND: Maximal inspiratory pressure (MIP) is often relied upon as an index of inspiratory muscle strength, and reproducibility of MIP taken to indicate maximal effort. This study was designed to determine whether reproducibility is a valid indicator of maximal effort. METHODS: Ten normal subjects were studied, all of whom were familiar with the MIP test but none was an experienced subject. They were told that the purpose was to measure how accurately they could generate 50% of their MIP. Each performed nine MIP efforts and nine submaximal efforts. Means and coefficients of variation of peak negative inspiratory pressure (Pmax) and the ranges of the best three efforts were calculated for each type. RESULTS: Mean (SE) Pmax averaged-93.8 (6.0) cm H2O for the maximal efforts and -60.6 (7.7) cm H2O for the submaximal trials, with coefficients of variation averaging 8.71 (1.75)% and 14.58 (2.63)%, respectively and the ranges averaging 6.5 (1.1)% and 13.4 (3.5)%, respectively. There was no clear separation between the coefficients of variation or ranges of maximal and submaximal efforts. In four cases the ranges of the best three submaximal efforts were less than 5 cm H2O and less than 5% -criteria that have been used to validate MIP results. These four subjects had lower ranges for submaximal than maximal efforts, even when expressed as percentages of the means. CONCLUSION: Reproducibility should not be relied upon to indicate a valid MIP test, especially for research purposes when relatively small changes in inspiratory muscle strength must be discriminated. PMID- 7886646 TI - Variability of peak expiratory flow rate in children: short and long term reproducibility. AB - BACKGROUND: Variability of peak expiratory flow (PEF) has been proposed as a surrogate for bronchial hyperresponsiveness. The normal range of variability of PEF for children has been reported and the test has been used to screen for asthma in population based studies. However, there is little information on the reproducibility of the method in epidemiological settings. METHODS: In a cohort study of primary school children the variability in PEF was recorded in two consecutive years for one week (first survey) and two weeks (second survey) using mini Wright peak flow meters. PEF was recorded twice daily (morning and evening) and average amplitude as a percentage of mean was calculated as a standard measure of PEF variability for each single week of PEF measurement. Children with PEF variability exceeding the 90% percentile of the distribution for the specific time period were regarded as having increased variability of PEF. RESULTS: Of 66 children with increased PEF variability in the first year, 13 (19.7%) had an abnormal test in the first week of the second year. Of 543 children with normal PEF variability in the first year, 44 (8.1%) had an abnormal test in the second study year (odds ratio 2.8, confidence interval (CI) 1.4 to 5.4). Of 646 children in the second survey 61 (9.4%) were abnormal during the first week and 68 (10.5%) had an increased PEF variability during the second week, but only 24 (3.7%) children had an increased PEF variability in both weeks. The sensitivity (specificity) for doctor-diagnosed asthma (12 month period prevalence) was 36.4% (91.0%) in the first week of the second survey. When measurements of both weeks of the second survey were used to calculate PEF variability there was little improvement in the sensitivity (38.1%) and specificity (91.5%), mainly because of decreased compliance in the second measurement week. CONCLUSIONS: In young children assessment of PEF variability in order to screen for asthma is of limited value because of the low reproducibility of the method. PMID- 7886648 TI - Effects of short term high frequency negative pressure ventilation on gas exchange using the Hayek oscillator in normal subjects. AB - BACKGROUND: The Hayek oscillator is a negative pressure cuirass that can operate at a range of frequencies to provide ventilation, and is a technique which could potentially be used on a general ward. This study examined the effect of different frequencies and different ranges of inspiratory and expiratory pressures on gas exchange, respiratory rate, and blood pressure in normal subjects. METHODS: Eight normal subjects received five minute periods of ventilation using the Hayek oscillator at five different frequencies, and a combination of two spans of inspiratory and expiratory pressures and two mean chamber pressures. A "sham" or control period was also performed at each frequency. Measurements were made of changes in gas exchange, spontaneous respiratory rate, and blood pressure before and after ventilation. RESULTS: There was significant intersubject variation in all results, independent of their height and weight. "Sham" settings acted as true controls in terms of gas exchange, but produced a fall in respiratory rate at 30 oscillations/min. The lower oscillatory frequencies of 30 and 60 oscillations/min produced the greatest increase in oxygenation, decrease in end tidal carbon dioxide pressure, and decrease in spontaneous respiratory rate. These effects were most significant at higher spans of pressure and were different from "sham" settings. No adverse effects were observed on blood pressure. CONCLUSIONS: The Hayek oscillator can provide assisted ventilation for short periods in normal conscious subjects with no adverse side effects on blood pressure. Maximal changes in gas exchange and a significant reduction in the spontaneous respiratory rate are seen when a combination of lower frequencies (30 and 60 oscillations/min) and higher spans of pressure are used. PMID- 7886649 TI - Effect of a spacer on pulmonary aerosol deposition from a jet nebuliser during mechanical ventilation. AB - BACKGROUND: Several factors have been identified which improve nebulised aerosol delivery in vitro. One of these is the addition of a spacer to the ventilator circuit which improves aerosol delivery from a jet nebuliser to a model lung by approximately 30%. The current study was designed to demonstrate whether similar improvements could be demonstrated in vivo. METHODS: Ten patients (seven men) were studied during mechanical ventilation (Siemens Servo 900C) after open heart surgery. Aerosol was delivered using a Siemens Servo 945 nebuliser system (high setting) driving a System 22 Acorn jet nebuliser (Medic-Aid) containing 3 ml technetium-99m labelled human serum albumin (99mTc-HSA (50 micrograms); activity in the first nebulisation, 90 MBq; in the second nebulisation, 185 MBq). Central and peripheral lung aerosol deposition and the time to complete deposition were measured using a gamma camera and compared when the nebuliser was connected to the inspiratory limb using a simple T-piece or a 600 ml spacer. RESULTS: The addition of the spacer increased total lung deposition (mean (SD) percentage initial nebuliser activity) from 2.2 (0.7)% to 3 (0.8)%. There was no difference in the time required to complete nebulisation (18.2 min v 18.3 min respectively for T-piece and spacer) or in the retention of activity in the nebuliser (46.2% v 47.1% respectively). CONCLUSIONS: The combination of a spacer with a jet nebuliser increased lung deposition by 36% in mechanically ventilated patients and is a simple way of increasing drug deposition or reducing the amount of an expensive drug required for nebulisation. PMID- 7886651 TI - The BTS and Doctors for Tobacco Law: working towards ending tobacco advertising. PMID- 7886650 TI - Comparison of the relative airways and systemic potencies of inhaled fenoterol and salbutamol in asthmatic patients. AB - BACKGROUND: There is controversy as to the relative safety of fenoterol and salbutamol. No differences have been found in the relative cardiac beta 1/beta 2 receptor activity of inhaled fenoterol and salbutamol in normal subjects. These initial findings have been extended by comparing the respective potencies of equivalent doses by weight of fenoterol and salbutamol in asthmatic subjects, in terms of airways and systemic responses. METHODS: Eighteen asthmatic patients of mean (SD) age 40 (14) years and a forced expiratory volume in one second (FEV1)% predicted of 56 (14)% (1.97 (0.66)1) were randomised to inhale fenoterol (100 micrograms/puff or 200 micrograms/puff), salbutamol, or placebo (100 micrograms/puff or 200 micrograms/puff) on three separate days. Dose-response curves were constructed using cumulative doses of 100 micrograms, 200 micrograms, 400 micrograms, 1000 micrograms, 2000 micrograms, and 4000 micrograms, and airways and systemic responses were measured 20 minutes after each dose with 40 minute increments. Dose ratios for the relative potency of fenoterol versus salbutamol were calculated from the dose-response curves using regression analysis of parallel slopes. RESULTS: There was no difference in bronchodilator potency between fenoterol and salbutamol (as median dose ratio): FEV1 1.1 (95% CI 0.4 to 4.6). In contrast, dose ratios for systemic responses showed that fenoterol was more potent than salbutamol: serum potassium 3.7 (95% CI 2.0 to 6.0), tremor 5.7 (95% CI 1.4 to 10.2), heart rate 1.6 (95% CI 1.0 to 2.3). At a conventional dose of 200 micrograms the only difference in response between the two drugs was observed for tremor (as mean difference): 0.23 log units (95% CI 0.06 to 0.41 log units). CONCLUSIONS: There was no difference in the bronchodilator potency between fenoterol and salbutamol on a microgram equivalent basis. In contrast, systemic potency was greater with fenoterol, although this difference was not clinically relevant at conventional dosages up to 200 micrograms. PMID- 7886652 TI - Comparative dose-response study of three anticholinergic agents and fenoterol using a metered dose inhaler in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: Inhaled anticholinergics and beta agonists are widely used in the treatment of patients with chronic obstructive pulmonary disease (COPD). However, dosage requirements have not been thoroughly evaluated and comparative dose response data for these agents are limited. METHODS: Twenty men with stable COPD of mean (SD) age 69.4 (5.8) years and FEV1 0.93 (0.38) litres were studied in randomised, double blind, crossover, placebo controlled experiments. All of the patients received two, four, eight, and 16 puffs of ipratropium bromide (20 micrograms/puff), flutropium bromide (30 micrograms/puff), oxitropium bromide (100 micrograms/puff), fenoterol (200 micrograms/puff), or placebo in random order on five separate days. Doses were administered by a metered dose inhaler at intervals of 60 minutes to give cumulative doses of two, six, 14, and 30 puffs. Five mg of nebulised salbutamol was administered 60 minutes after the patient had received the final 16 puffs of each regimen. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), heart rate, and blood pressure were measured five minutes before each treatment and 30 minutes after treatment with nebulised salbutamol. RESULTS: FEV1 and FVC reached a plateau after administration of a cumulative dose of 14 puffs of ipratropium bromide (280 micrograms) or flutropium bromide (420 micrograms), and after six puffs of oxitropium bromide (600 micrograms). There were no differences with respect to maximum increases in FEV1 and FVC amongst the three anticholinergic agents. However, after six puffs oxitropium bromide produced a greater increase in FEV1 than either ipratropium bromide or flutropium bromide. Fenoterol caused a greater increase in both FEV1 and FVC than the three anticholinergic agents after six puffs, as well as a greater increase in pulse rate. Oxitropium bromide produced a greater increase in pulse rate than the other anticholinergics after 14 puffs. The incidence of side effects was dose-related and notable adverse effects were reported after 30 puffs of ipratropium bromide, 14 puffs of oxitropium bromide, and two puffs of fenoterol. CONCLUSIONS: Oxitropium bromide produced a greater bronchodilator effect than either ipratropium bromide or flutropium bromide when used at doses of less than six puffs, without apparent side effects. There were, however, no differences in maximal response between these drugs. Fenoterol may have a greater peak bronchodilator effect than the anticholinergic agents but it causes more adverse effects, even at lower doses. Depending upon the balance between efficacy and side effects, oxitropium bromide may be preferred in the treatment of patients with COPD. PMID- 7886653 TI - Reduction in leukotriene B4 generation by bronchoalveolar lavage cells in asthma. AB - BACKGROUND: Leukotrienes are inflammatory mediators implicated in the pathogenesis of asthma. The capacity of inflammatory cells within the airways to generate leukotrienes may be altered in asthma. This hypothesis was tested using bronchoalveolar lavage (BAL) to sample cells within the airways from atopic asthmatic and normal subjects, and by measuring their capacity to generate leukotriene B4 (LTB4) and leukotriene C4 (LTC4) in response to A23187, a potent stimulus of leukotriene generation. METHODS: Bronchoalveolar lavage was performed in 12 mild asymptomatic atopic asthmatic patients and 12 normal subjects. Mixed BAL cell aliquots (approximately 80% alveolar macrophages) were incubated with 0 20 microM A23187 for 10 minutes and with 4 microM A23187 for 0-30 minutes, and leukotrienes were measured by radioimmunoassay and high performance liquid chromatography. RESULTS: Mixed BAL cells from asthmatic subjects generated less LTB4 than cells from normal subjects in dose response and time course experiments (area under the curve 81.5 (0.0-228.5) ng.min.10(-6) cells in asthmatic subjects and 197.9 (13.9-935.6) ng.min.10(-6) cells in normal subjects. There were no differences in LTC4 generation between BAL cells from asthmatic and normal subjects. CONCLUSIONS: Generation of LTB4 by BAL cells from atopic asthmatic subjects in response to A23187 was reduced. As the alveolar macrophage is the major source of LTB4 in BAL cells, these results probably reflect reduced generation of LTB4 by alveolar macrophages from asthmatic patients. This may be a consequence of monocyte migration into the lung, or altered alveolar macrophage function in asthma, or both. PMID- 7886654 TI - Home environment and asthma in Kenyan schoolchildren: a case-control study. AB - BACKGROUND: There is increasing evidence that environmental factors contribute to the development of asthma, so the relationship was studied between home environment factors and asthma among school children of varying socioeconomic backgrounds living in a developing country. METHODS: A case-control study was performed in participants of a prevalence survey which included 77 schoolchildren with asthma (defined by a history of wheeze, doctor diagnosis, or a decline in FEV1 of > or = 10% at five or 10 minutes after exercise) and 77 age and gender matched controls. Subjects were selected from 402 school children aged 9-11 years attending five primary schools in the city of Nairobi who participated in a prevalence survey of asthma. Visits were made to the homes of cases and controls and visual inspection of the home environment was made using a checklist. A questionnaire regarding supplemental salt intake, parental occupation, cooking fuels, and health of all children in the family was administered by an interviewer. RESULTS: In multivariate analysis the following factors were associated with asthma: damage caused by dampness in the child's sleeping area (adjusted odds ratio (OR) 4.9; 95% confidence interval (CI) 2.0 to 11.7), air pollution in the home (OR 2.5; 95% CI 2.0 to 6.4), presence of rugs or carpets in child's bedroom (OR 3.6; 95% CI 1.5 to 8.5). Children with asthma reported a supplemental mean daily salt intake of 817 mg compared with 483 mg in controls. CONCLUSIONS: Home environmental factors appear to be strongly associated with asthma in schoolchildren in a developing nation. These findings suggest a number of hypotheses for further studies. PMID- 7886655 TI - An open, prospective comparison of beta 2 agonists given via nebuliser, Nebuhaler, or pressurised inhaler by ambulance crew as emergency treatment. AB - BACKGROUND: The merits of the use of beta 2 agonists by ambulance crew and best methods of delivery have not been fully explored. METHODS: A prospective comparison has been made of treatments applied in three districts in South Wales (200 micrograms salbutamol by pressurised inhaler, 5 mg salbutamol via nebuliser, and 5 mg terbutaline via Nebuhaler) by emergency ambulance personnel to acutely wheezy patients en route to hospital. Pulse rate, respiratory rate, peak expiratory flow rate (PEFR), and breathlessness scored on a visual analogue scale were compared before and after treatment. Data were collected on diagnosis, artificial ventilation, cardiorespiratory arrest, and death. RESULTS: Thirty eight patients received salbutamol inhaler, 51 salbutamol via nebuliser, and 41 terbutaline via Nebuhaler. There were greater reductions in respiratory rate and breathlessness score and more improvement in PEFR in the group receiving nebulised salbutamol than in the other two groups. No patient was ventilated and of the five deaths none was caused by asthma. CONCLUSIONS: For wheezy, breathless patients treated en route to hospital by emergency ambulance personnel, 5 mg salbutamol given by an oxygen-driven nebuliser was more effective than either 5 mg terbutaline via a Nebuhaler or 200 micrograms salbutamol via a pressurised inhaler. PMID- 7886656 TI - Effectiveness of nebulised salbutamol administered in ambulances to patients with severe acute asthma. AB - BACKGROUND: Nebulised salbutamol can now be administered by ambulance personnel to patients with severe acute asthma en route to hospital. This treatment, however, is not yet available in all ambulances. The safety and effectiveness of allowing ambulance crews to initiate treatment with nebulised salbutamol has been assessed in patients with acute severe asthma. METHODS: After a basic training course in the assessment of asthma and the use of a nebuliser, ambulance crews initiated treatment with nebulised salbutamol in asthmatic patients under the age of 40 years. Airflow obstruction was measured before and after treatment with a peak flow meter. A subjective assessment of any change in the patient's condition was also made. RESULTS: Nebuliser treatment was associated with a significant increase in peak flow in almost 80% of patients who had recordable values before and after treatment. The mean percentage increase in peak flow was 56.5%. Subjective assessments correlated well with peak flow measurements. No unwanted side effects were recorded. CONCLUSIONS: Nebulised salbutamol is an effective and safe treatment for acute asthma when administered by ambulance personnel after a short training course. PMID- 7886657 TI - District nebuliser compressor service: reliability and costs. AB - BACKGROUND: There is little information on the costs of maintaining a district nebuliser compressor service. This retrospective study examines the issue, reliability, and maintenance costs of electrical compressors to assist the prediction of future costs, taking into account recent safety legislation. METHODS: Records of issue, repair, and replacement for the period 1982-91 were reviewed. The current policy of repairing and replacing as necessary, and three other theoretical costings, were considered. RESULTS: The number of compressors being issued is increasing. Repaired compressors are less reliable and frequency of repair is a function of compressor age. The current policy is the most cost effective. CONCLUSIONS: To repair and replace nebuliser compressors as necessary is the most economical policy under the present terms offered by the manufacturers, but changes in safety legislation will affect the provision of such services. PMID- 7886658 TI - Contribution of multiple inert gas elimination technique to pulmonary medicine. 6. Ventilation-perfusion relationships during anaesthesia. PMID- 7886659 TI - Detection of human cytomegalovirus antigenaemia: a rapid diagnostic technique for predicting cytomegalovirus infection/pneumonitis in lung and heart transplant recipients. AB - BACKGROUND: New rapid diagnostic techniques offer the opportunity of early diagnosis of human cytomegalovirus (CMV) infection in immunocompromised patients at risk of developing CMV disease. The use of human CMV antigenaemia as a predictor of clinical CMV infection and disease in lung and heart transplant recipients was studied prospectively. METHODS: Twenty three heart and nine lung transplant recipients who survived 40 days were observed by standard CMV surveillance with serological testing, culture, and by sequential testing for CMV antigenaemia. CMV antigenaemia testing is a rapid and quantifiable technique in which a viral lower matrix protein is detected in cytospin preparations of peripheral blood polymorphonuclear leucocytes (PMNLs) by immunofluorescent staining. RESULTS: Eleven patients developed CMV infection and five developed CMV disease (four pneumonitis, one duodenitis). These clinical events occurred at a median of 65 days following transplantation. CMV antigenaemia occurred in 17 patients at a median of 35 days following transplantation. Detection of CMV antigenaemia had a sensitivity of 100%, a specificity of 93.7%, and a positive predictive value of 94.1% for CMV related illness. CMV antigenaemia was positive at a significant interval before the clinical event. High levels of CMV antigenaemia (> 50 CMV antigen positive cells/2 x 10(5) PMNLs) occurred in 11 patients and five of these developed disease. CMV antigenaemia of > 50 CMV antigen positive cells/2 x 10(5) PMNLs had a positive predictive value of 45.5% for disease but a negative predictive value of 100%. Patients with disease had higher levels of antigenaemia than those without disease. CONCLUSIONS: CMV antigenaemia is a rapid diagnostic technique which can identify patients likely to develop CMV disease, potentially allowing early treatment. PMID- 7886660 TI - Pulmonary endocrine cells in plexogenic pulmonary arteriopathy associated with cirrhosis. AB - A clear association has been described between numbers of pulmonary endocrine cells and the migration and/or proliferation of myofibroblasts which is thought to underlie the vascular changes seen in plexogenic pulmonary arteriopathy due to cardiac shunts and primary pulmonary hypertension. In contrast, the pulmonary endocrine system in a subject with florid pulmonary plexogenic arteriopathy associated with cirrhosis was entirely normal, suggesting possible differences in its pathogenesis. PMID- 7886662 TI - Pulmonary vascular reactivity in severe pulmonary hypertension associated with mixed connective tissue disease. AB - Pulmonary vascular reactivity tests were performed in a young woman with mixed connective tissue disease and severe pulmonary hypertension. Vasoreactivity was documented in response to intravenous prostacyclin (PGI2), oral nifedipine, and inhaled nitric oxide, with quantitative differences. Nitric oxide produced a moderate lowering of pulmonary arterial pressure and resistance without any deleterious systemic effect. The use of nitric oxide in testing for pulmonary vasoreactivity merits further evaluation. PMID- 7886661 TI - Pulmonary vascular involvement in neoplastic angioendotheliosis. AB - Neoplastic angioendotheliosis has rarely been described as a respiratory disease. A patient is described with pulmonary vascular involvement induced by neoplastic angioendotheliosis in pulmonary vessels. PMID- 7886663 TI - Pulmonary haemorrhage following renal transplantation. AB - The case history is presented of a 32 year old black man who developed haemoptysis leading to pulmonary haemorrhage and bilateral pulmonary infiltrates. He was found to have Kaposi's sarcoma of the lung with no evidence of skin or endobronchial lesions. PMID- 7886664 TI - [Veterinary medicine and organic animal husbandry. I. Organic animal husbandry in The Netherlands]. AB - Organic agriculture is increasingly of interest. The first organic farm in the Netherlands was established 70 years ago. Since then, the practice of this type of agriculture has grown. Although still relatively small scale, organic farming has a potential that is recognized in practice, in agricultural policies, and by the public. PMID- 7886665 TI - [Veterinary medicine and organic animal husbandry. II. Organic animal husbandry: a challenge for veterinary medicine]. AB - Biological agriculture serves as an example on an endeavour to achieve durability. Government policies offer possibilities for the further development of biological animal husbandry. Biological veterinary practice places emphasis on the promotion of animal health, rather than on the treatment of disease. Because the aim is to reduce medication, this goal is consistent with the approach of biological animal husbandry. These new developments are of interest to veterinary practitioners and require professional knowledge to be adapted to the biological way of thinking. PMID- 7886666 TI - [Veterinary medicine and organic animal husbandry. III. Animal health in organic dairy farms]. AB - Animal health is dealt with differently on biological farms then on conventional farms. On biological farms, stockmen see their animals not only as individual animals, but also as part of a herd in a balanced ecosystem. Disease prevention is therefore given much thought. The use of medicines is selective and subjected to strict regulations. This paper presents a summary of disease incidence in dairy cattle on biological farms and highlights specific problems and problem prevention in biological animal husbandry. PMID- 7886667 TI - [Report from an evacuated veterinarian. '4 weeks in a new practice and all animals are gone!']. PMID- 7886668 TI - [Pioneers: veterinarians from earlier times (8). Francisco de la Reyna]. PMID- 7886669 TI - [DNA ploidy]. PMID- 7886670 TI - The effect of sex hormones on lipid content and mast cell number in the harderian gland of the female toad, Bufo viridis. AB - The Harderian gland of the toad Bufo viridis is a dimorphic gland owing to the presence of lipid droplets in the female glandular cells present only during summer months. Ovariectomy causes the disappearance of sudanophilia and estrogen treatment completely prevents this change, while testosterone-injection has little effect. Estradiol-treatment also provokes a proliferation of the interstitial connective tissue concomitantly with the mast cell number increase. Our results suggest that estradiol acts, stimulating both mast cell and connective tissue proliferation, and plays a role in determining the expression of the female type of the toad Harderian gland. PMID- 7886671 TI - Regeneration of the endothelium in the canine and feline thoracic duct. AB - Recent improvements in microsurgical techniques on lymphatic vessels facilitated the treatment of lymphoedema. But it is becoming clear that a successful treatment of lymphatic disease has to be based on knowledge of ongoing processes. Particularly, one of the important and unclear issue is cellular mechanisms of lymphatic regeneration. The regeneration of endothelial and the smooth muscle cells of the thoracic duct has been experimentally tested in vivo. The canine and feline thoracic duct was cryo-injured using 3 mm-based copper rod. Damaged endothelial cells remained attached to the substrate and lost unthrombogenecy within 48 hr. Adjacent EC restored the defect within 3 days by migration and proliferation. We observed that on the first day, the endothelial monolayer included some elongated multinuclear cells with blind silver lines whereas, on the third day, they were replaced by a population of smaller ECs with numerous mitoses. Organization of the monolayer was restituted within 7 days. The newly formed endothelium was similar to regenerating endothelium of arteries. In general, the clot that appeared at the zone of injury on the second day was dissolved by the third day. Occasionally, the dense polymorphic clot adhered to the wall and caused a delay in reendothelisation. Complete restitution of the tunica media which involved migration and proliferation mechanisms accompanied the endothelium regeneration. PMID- 7886672 TI - Ultrastructural, histochemical and electrophysiological study of calf gallbladder epithelium. AB - Calf (Bos taurus) gallbladder, contrary to that of most mammalian, does not concentrate bile. It is to be ascertained whether this phenomenon is the result of a lack of fluid absorption or a balance between the latter and fluid secretion. To this end we began a characterization of bovine gallbladder epithelium by means of electron microscopy, immunocytochemistry, enzymatic activity and electrophysiological measurements. We also partially characterized bile content. The ultrastructural examination showed that surface epithelial cells have the general structure that is observed in absorptive epithelia. Mucous secretory activity is also evident. Moreover, two distinct types of secreting cells line the glands in the lamina propria and contribute to the production of an abundant secretion. The cell surface shows a marked reactivity with the anti alkaline phosphatase serum. Most of the activity of alkaline phosphatase and L gamma-glutamyltransferase is found at the apical side of the epithelium. Electrophysiological parameters indicate that this is a low resistance epithelium. Therefore, coexistence of features typical of absorptive epithelia and the inability of concentrating bile suggest that, in this organ, fluid absorption and secretion are both present. PMID- 7886673 TI - Calmodulin binding proteins in the membrane vesicles released during the acrosome reaction and in the perinuclear material in isolated acrosome reacted sperm heads. AB - Calmodulin has been suggested as the Ca(2+)-mediator in diverse cellular functions via its interaction with a number of proteins in a calcium-dependent manner. Its participation in the acrosome reaction has been suggested based on its localization in the acrosome region, on the effects produced by calmodulin antagonists, and by the changes in calmodulin compartmentation observed to occur throughout guinea pig acrosome reaction. To define the role of calmodulin in the membrane fusion events that occur during the acrosome reaction, the identification of calmodulin-binding proteins, by the overlay technique with biotinylated or unmodified calmodulin, was made in the following sperm fractions: in the membrane vesicles released during the acrosome reaction, in the remaining perinuclear material of acrosome reacted sperm heads and in a total membrane fraction from intact spermatozoa. The membrane vesicles released after the acrosome reaction showed four major calmodulin-binding proteins, M(r)s 66, 95, 97 and 110 kDa. The perinuclear material showed a 31-34, 43 and 97 kDa calmodulin binding polypeptides. The membrane fraction from intact sperm showed eleven calmodulin-binding proteins, M(r)s between 14-110 kDa. Most of the binding proteins detected by this method corresponded to the class of calcium-independent calmodulin-binding proteins but proteins which only interacted with calmodulin in a calcium-inhibited mode were also observed. No calcium-dependent calmodulin binding proteins were detected in any of the fractions studied. A possible role of these binding proteins in calmodulin compartmentation is discussed. The potential role of these binding proteins in membrane fusion and in membrane receptor localization in the postacrosomal region remain to be defined. PMID- 7886674 TI - Oogenesis in a placental viviparous onychophoran. AB - This first ultrastructural study of oogenesis in a placental viviparous onychophoran describes oocyte differentiation, cell interactions and reveals various unusual cellular features. The viviparous onychophoran Plicatoperipatus jamaicensis has paired ovaries medially located, attached to the dorsal body wall by muscular terminal filaments. The rest of the female reproductive tract consists of paired spermathecae oviduct/uteri (hereafter referred to as uterus). Bulbous spermathecae are joined to the oviducts by ducts. Also continuous with the oviduct lumen are two tubular structures whose lumina open to the hemolymph. The uteri contain a progression of developmental stages from implantation through stalked morulae, blastocysts, larvae and juveniles about to be born. Growing oocytes are characterized by large germinal vesicles showing synaptonemal complexes. Oocytes are surrounded by flattened follicle cells that possess extensive bundles of thick and thin filaments. Mature oocytes contain little or no yolk, but are unique among organisms in accumulating a large central reservoir of stored glycogen. The lack of yolk reflects the placental viviparous nature of the reproductive process. The glycogen reservoir provides a rapidly accessible energy source for early developmental stages. Particularly prominent also are unusually extensive and highly elaborate Golgi complexes in the cortical and peri nuclear ooplasm. While extensive Golgi complexes have been described in oocytes of a variety of species, the particularly exaggerated size and amount of Golgi in these onychophorans suggests they may provide excellent material for the study of Golgi function. The features of the oocyte and placental viviparity show this is an ideal model to investigate the nature of the placental reproductive process analogous to mammals in an invertebrate and its implications to oogenesis. PMID- 7886675 TI - Identification of insulin-like peptides in cerebral ganglia neurosecretory cells of the mussel Mytilus edulis. AB - The immunostaining patterns of cerebral ganglia sections from the mussel Mytilus edulis with monoclonal antibodies raised against cerebral ganglia (CG) extracts were compared to those obtained with various polyclonal anti-insulin-like antibodies. One of the monoclonal antibodies (MAB 46) revealed clusters of positive cells in localization comparable to those revealed by the polyclonal antibodies. The nature of the antigen recognized by MAB 46 and the polyclonal antibodies was compared by gel filtration-HPLC of a cerebral ganglia extract. Similar peaks were revealed by the monoclonal and polyclonal antibodies. MAB 46 significantly inhibited the cerebral ganglia induced stimulation of amino-acid incorporation by mantle edge cell suspensions, suggesting that the antigen recognized by MAB 46 is involved in the control of growth. PMID- 7886676 TI - Quantification of tight junction complexity by means of fractal analysis. AB - The concept of fractal geometry provides an elegant tool for the quantitative and objective structural description of various objects, the fractal analysis. Fractal analysis quantifies the structural complexity of objects by a characteristic singular value, the fractal dimension (FD). It can be estimated, e.g. by the box-counting method and provides a highly integrated measure in the range 1 < FD < 2 for curves extending within a plane. In this study, fractal analysis is used for the first time to evaluate the complexity of the tight junction network between adjoining cells. Bovine brain endothelial cells were cultured under various experimental conditions and the tight junctions were drawn to scale as visualized by the freeze fracture technique. These drawings were analyzed by fractal analysis, and by two other methods commonly used in this field, viz. the strand counting (SC) and complexity index (CI) methods. In contrast to the latter methods, the FD shows no directional preference and therefore no assumptions on the dynamic properties of the network's complexity are required. Thus, FD is demonstrated to provide the most sensitive, reliable and complete measure of tight junction complexity. In combination with SC and CI, additional information can be achieved concerning the directionality of the altered arrangement of tight junctional strands. Our analysis allows for the following conclusions. (1) Defined experimental influences can modify the complexity of tight junctions that are formed between endothelial cells in vitro, and (2) these structural modifications of the tight junctions are mainly due to an altered strand branching pattern. PMID- 7886677 TI - Septate-like junctions in the normal male rat pituitary gland. AB - Septate-like junctions were observed in the rat anterior pituitary gland of the adult male solely between adjacent folliculo-stellate cells. Considering their location, it is presumed that their function is cellular adhesion and mechanical support for the hypophyseal follicles. PMID- 7886678 TI - Morphological changes in the rat Sertoli cell induced by the microtubule poison carbendazim. AB - Early morphological changes in the rat Sertoli cell induced by the fungicide carbendazim (methyl-2-benzimidazole carbamate; MBC), a metabolite of benomyl, were examined. Adult rats were treated with single doses of MBC (400 mg/kg) or vehicle and examined by light and electron microscopy at 3 hr post-treatment. Sloughing of elongating spermatid clusters was observed in all stages of spermatogenesis, except for Stages III-V. Cleavage occurred near the apical region of the seminiferous epithelium where cytoplasmic processes of the Sertoli cell surround the heads of elongating spermatids. The cleaved cytoplasm remained attached to the sloughed spermatids and ectoplasmic specializations remained undamaged. Intact microtubules were observed in the apical Sertoli cell cytoplasm (including sloughed tissues) but were decreased in the body region, where aggregates of mitochondria were found. Cytoplasm near the cleavage site exhibited rarefaction, which was associated with swollen cisternae of endoplasmic reticulum. It appears that the mechanism of germ cell sloughing induced by MBC treatment involves the disruption of microtubules in the body region of the Sertoli cell, the retraction of cytoplasmic organelles and the swelling of endoplasmic reticulum. PMID- 7886679 TI - Phenotypic characterisation of rat striatal neurones in primary culture. AB - The aim of this study was to determine to what extent the neuronal phenotypes present in primary cultures of rat striatal neurones correspond to those present in vivo. A large percentage of cultured striatal neurones contained relatively high levels of proenkephalin mRNA. In addition, a high level of expression was found for the prosomatostatin mRNA. Protachykinin mRNA and proneuropeptide Y mRNA were also expressed, but at a comparatively low level. No prodynorphin mRNA could be detected. Considerable numbers of neurones were also found to express NADPH diaphorase activity, while a smaller number of neurones were positive for acetylcholinesterase. The NADPH-diaphorase and the acetylcholinesterase could be detected both in cell bodies, and in neuronal processes contacting groups of neighbouring neurones. Since nitric oxide does not require synaptic specialisations to exert its intercellular actions, this provides strong evidence that NADPH-positive neurones communicate with other cells in primary culture. These observations demonstrate that when striatal neurones are grown in primary culture, a range of neurochemical phenotypes are present which correspond closely to those present in the mature striatum in vivo. Together with the evidence for cell-cell interactions, this suggests that primary striatal cultures will provide a suitable model to study the molecular mechanisms controlling striatal function. PMID- 7886680 TI - Selective isolation of rat aortic wall layers and their cell types in culture- application to converting enzyme activity measurement. AB - The rat aorta, whose three wall layers can be separated by microdissection offers the rare possibility of comparing physiological characteristics of in vivo tissular cell components and corresponding cells after culture. We developed a technique allowing the dissociation of the three tunicae (intima, media and adventitia) of the rat aorta and the culture of their main cell types, i.e.: endothelial cells (EC) from intima, smooth muscle cells (SMC) from media and fibroblasts (Fib) from adventitia. Comparison between selected tunicae in vivo and their corresponding cells in vitro was performed via arterial angiotensin converting enzyme (ACE) activity measurements in Wistar rats. In vivo microsomial ACE activity for each tunica was as follows: 368.9 +/- 34.3 (endothelium), 10.5 +/- 1.9 (media) and 10.2 +/- 4.9 (adventitia) pmol/mg protein/min. Corresponding cell primary culture values were 1.2 +/- 0.1 (EC), 0.06 +/- 0.02 (SMC) and 0.24 +/- 0.01 (Fib) pmol/mg protein/min. Incubation of serum-deprived cells with Dexamethasone (10(-7) M) over 48 hr induced a statistically significant shift of total ACE activity from controls to stimulated cells of 2.9 +/- 0.3 to 9.7 +/- 1.0 in EC, 0.8 +/- 0.1 to 32.1 +/- 4.9 in SMC and 1.03 +/- 0.65 to 57.2 +/- 2.1 pmol/mg prot/min in fibroblasts. In the rat aorta, ACE was present not only in the intimal endothelial cell lining, but also in the media and the adventitia. ACE activity levels in primary cultured vascular cells were about 100-fold less than those found in the ex vivo tissues. Nevertheless, ACE expression seems to be more constitutive in endothelial cells and more inducible in smooth muscle cells and fibroblasts. This methodological approach should be of interest in studying environmental or genetic regulation of protein expression in the three layers/three cell types of the vascular wall. PMID- 7886681 TI - Study on the embryofeto-toxicity of citral in the rat. AB - Citral, 3,7-dimethyl-2,6-octadien-1-al, found in the essential oils of a large variety of useful plants, is used as a scenting agent in household products, as a fragrance in cosmetics, and as a food flavouring additive. This study was undertaken to investigate the embryofeto-toxic potential of citral in the rat. Citral (60; 125; 250; 500 and 1000 mg/kg) in corn oil was given orally to Wistar rats from day 6 to 15 of pregnancy. Caesarean sections were carried out on day 21 of pregnancy, and the number of resorptions and implantation sites were recorded. Fetuses were weighed, examined for external malformations, and fixed for visceral examination, or cleared and stained with Alizarin Red S for skeleton evaluation. A transient decrease in weight gain from days 6 to 11 of gestation at the lowest doses, and a reduction in body weight minus uterine weight at term at the highest doses, indicated that citral was maternally toxic over the dose range tested. A slight but statistically significant increase in the ratio of resorptions per implantations was observed with 60 and 125 mg/kg body weight. Doses higher than 125 mg/kg reduced dose-dependently the ratio of pregnant per mated female. Signs of fetal growth retardation and a higher incidence of minor skeletal abnormalities were found in doses higher than 60 mg/kg. No increase in the frequency of visceral anomalies was found at any dose level, but an increase in fetal spleen weight was observed in doses higher than 125 mg/kg. Therefore, data presented in this paper indicate that the no-observed adverse effect level for embryofeto-toxicity is lower than 60 mg citral/kg body weight p.o. PMID- 7886683 TI - Comparison of the induction of rat glutathione S-transferase and fatty acid ethyl ester synthase activities. AB - Fatty acid ethyl esters (FAEE) are formed following the administration of ethanol and have previously been associated with toxicological effects in animals and humans. It has been suggested that the enzyme responsible, FAEE synthase, has both structural and catalytic properties very similar to a glutathione S transferase (GST). Since GSTs are inducible, their induction could be associated with enhanced FAEE formation and toxicity. In the present study, rats were administered beta-naphthoflavone, phenobarbital, ethanol, or Aroclor 1254, and hepatic FAEE synthase and GST activities were measured. beta-Naphthoflavone and ethanol did not induce either activity. Phenobarbital increased GST activity in the liver but not in lung or pancreas. Only Aroclor 1254, which increased GST activity in liver and pancreas, increased FAEE synthase activity and then only in the liver. Thus, in comparison with GST activity, FAEE synthase activity is very limited in its ability to be induced. PMID- 7886682 TI - 4-Maleimidohippuric acid--a tailor-made, direct, site-specific nephrotoxin: effects on renal function and ultrastructure in pentobarbital-anesthetized dogs. AB - A model has been proposed to explain at least one of the possible pathways through which a xenobiotic might produce proximal tubule necrosis. The model is formulated on the idea that a compound must possess two structural features: (i) a carboxyl or amino acid moiety that would allow for selective uptake into proximal tubule cells via the strategically located antiluminal membrane-bound organic anion transport system or the luminal membrane-bound amino acid transport system(s), respectively, and (ii) a highly reactive moiety that can directly alkylate proximal tubular components, or a moiety that can be biotransformed within proximal tubular cells to such a substance. In an attempt to validate the proposed structural features as prerequisites for xenobiotic induction of proximal tubular necrosis, a novel compound, 4-maleimidohippuric acid (4-MHA), was synthesized which possesses an anionic group and a reactive moiety. Following the administration of 4-MHA directly into the renal artery of pentobarbital anesthetized dogs, specific unilateral ultrastructural damage was noted only in the S1 and S2 cell types of the proximal tubule; the most notable renal function changes included proteinuria and glucosuria. Anionic, but non-alkylating, relatives of 4-MHA failed to alter renal function or ultrastructure. The specific proximal tubular toxicity of 4-MHA validates the proposed structural requirements for induction of proximal tubular necrosis. PMID- 7886684 TI - The effects of long-term oral administration of ethanol on Sprague-Dawley rats--a condensed report. AB - For a period of 2 years Sprague-Dawley rats received 3% and 1% ethyl alcohol or an equicaloric amount of glucose in a semisynthetic liquid diet. Thereafter the tumour incidence was recorded. For male rats no neoplastic lesions were observed to be related to ethanol exposure. For females, when individual group comparisons were made, an increase in mammary gland tumours was seen for females receiving the low ethanol containing diet. In some tumour frequency comparisons the opposite, namely a decrease in the rate of incidence, was obtained. The overall information seems to indicate the absence of a carcinogenic activity of ethyl alcohol per se after long-term oral administration. Liver and bile duct injury was seen among males. Inflammatory reactions were seen among males in pancreas and for females in the clitoral gland. Hyperplasia was observed in the thyroid gland in both sexes and in the adrenal glands among females. Peripheral nerve degeneration was common in both sexes. PMID- 7886686 TI - Dietary vitamin A enhances sensitivity of the local lymph node assay. AB - Murine assays such as the mouse ear swelling test (MEST) and the local lymph node assay (LLNA) are popular alternatives to guinea pig models for the identification of contact sensitizers, yet there has been concern over the effectiveness of these assays to detect weak and moderate sensitizers. Much work has been done to improve the sensitivity of the MEST, including the addition of a vitamin A acetate (VAA) enriched diet, which increases its sensitivity. Vitamin A acetate has been reported to increase the numbers of Langerhans cells (antigen presenting cells) in the skin, which could in turn enhance the cellular immune response. Because the LLNA relies on tritiated-thymidine incorporation by proliferating T cells during the induction phase, we have studied the potential of the VAA diet to enhance sensitivity of the LLNA. Results indicate that the VAA enriched diet significantly increased the LLNA sensitivity to formalin, eugenol, glutaraldehyde, trimellitic anhydride, and an azo dye at concentrations where no proliferation was observed in mice maintained on the standard diet. Maintenance on a VAA diet for 3 weeks prior to initiating the sensitization procedure was optimal. Thus, incorporation of a VAA diet improves the sensitivity of the LLNA as a quick, objective, and relatively inexpensive screen for detecting moderate and weak contact sensitizers. PMID- 7886685 TI - Immunotoxicological investigation using pharmaceutical drugs. In vitro evaluation of immune effects using rodent or human immune cells. AB - In order to evaluate the relevance of in vitro methods for immunotoxicity assessment, the effects of pharmaceutical drugs on lymphoproliferative and cytotoxic functions of mouse splenocytes and human peripheral blood mononuclear cells (hPBMC) were studied. A comparison of sensitivity of immune cells from different origins to an in vitro exposure to different xenobiotics was performed using non-immunosuppressive (cimetidine and furosemide) and immunosuppressive (azathioprine (AZA), cyclosporine A (CSA), and dexamethasone (DEX)) drugs. For CSA, sensitivity of both rat and mouse splenocytes following in vitro exposure was compared to the one of hPBMC. Immune function tests included lymphoproliferative response to mitogenic lectins (concanavalin A (Con A) and phytohemagglutinin (PHA-P)) or to allogeneic cells (mixed leukocyte response (MLR)) and cytotoxicity assays (cytotoxic-T lymphocyte (CTL) and natural killer (NK) cell-mediated cytolysis). Additionally, to evaluate how well in vitro assays represent the in vivo situation, a comparison of the effect of cyclosporine A on the same immune function tests following in vivo or in vitro exposure was performed. The data obtained show numerous similarities in the effects observed following in vitro exposure of rodent or human cells to the drugs and a very similar sensitivity of rat and mouse cells to CSA in vitro. Discrepancies between human and rodent cells such as lymphoproliferative response to PHA-P following exposure to DEX or sensitivity of CTL-mediated cytolysis to CSA do exist. In vitro assays were very representative of the in vivo situation, both in the rat and in the mouse, following CSA exposure, except for NK cell activity in the rat. These data show the usefulness of in vitro systems for immunotoxicity assessment. They allow direct comparison of rodent and human systems, and could be representative, for drugs altering specifically the immune system like CSA does, of the in vivo situation. PMID- 7886687 TI - Comparison of ketoconazole- and fluconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. AB - Ketoconazole (KT) and fluconazole (FLU) are azole antifungal agents with a broad spectrum of activity against both superficial and systemic mycoses. KT is also an anticancer agent in the treatment of advanced prostate cancer. In many clinical and retrospective studies, KT has been reported to cause liver damage, i.e. chemical hepatitis. Histologic analysis of KT induced hepatotoxicity shows massive centrilobular necrosis in which the hepatotoxicity was not thought to be mediated through an immunoallergic mechanism. According to the medical literature, the pattern of hepatic injury appears to be primarily of the hepatocellular type. Because of the documented reports of KT and FLU hepatotoxicity, a cytotoxicity comparison of KT and FLU was implemented. The objective of this comparison was to evaluate the cytotoxicity of these azoles such that future mechanistic investigations of hepatotoxicity could be performed. The relative hepatotoxicity of KT and FLU was evaluated using primary cultures of postnatal rat hepatocytes. Cytotoxicity was evaluated by measuring the leakage of the cytosolic enzyme, lactate dehydrogenase (LDH), into the medium; by assessing mitochondrial reduction of 3-(4,5-dimethythiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT); by assessing lysosomal uptake of neutral red (NR); and by gross morphology (phase contrast microscopy). The cultures were exposed to various concentrations of KT (56-188 microM) for 0.5-4 h and to various concentrations of FLU (50 microM to 1.0 mM) for 0.5-6 h. There was a significant increase (P < 0.05) in LDH leakage and a large decrease in MTT reduction and lysosomal uptake of NR at 4 h for KT. One millimolar FLU had minimal effects on the LDH leakage and MTT reduction. These results demonstrate that KT is a more potent cytotoxicant than FLU; and its toxicity was expressed in a dose- and time dependent manner. PMID- 7886688 TI - Dichlobenil in the fetal and neonatal mouse olfactory mucosa. AB - The irreversible binding and toxicity of the olfactory toxicant dichlobenil in the mouse perinatal olfactory mucosa were examined by autoradiography and histopathology. In the olfactory mucosa of adult mice the irreversible binding of [14C]dichlobenil-derived radioactivity is confined to the Bowman's glands. The results in this study showed a low irreversible binding of [14C]dichlobenil derived radioactivity in the fetal olfactory mucosa from day 17 of gestation and a markedly increased binding after birth in accord with the development of the Bowman's glands. No morphological changes were observed in the olfactory mucosa of 1- or 4-day-old neonates given s.c. injections with dichlobenil 12 mg/kg but in 8- or 11-day-old mice given 12 or 25 mg/kg, scattered necrotic Bowman's glands occurred in the dorsomedial olfactory region 24 h after administration. In adult male mice dosed i.p. with dichlobenil a more extensive toxicity in the Bowman's glands was observed. The low toxicity of dichlobenil in the postnatal olfactory mucosa, despite a high irreversible binding at this site, may possibly be related to the cell proliferation in the developing olfactory mucosa leading to replacement of damaged cells. PMID- 7886689 TI - The life and viper of Dr Patrick Russell MD FRS (1727-1805): physician and naturalist. AB - It is nearly two hundred years since the publication in 1796 of An Account of Indian Serpents collected on the Coast of Coromandel by Patrick Russell. Within the folio is a drawing and description of the venomous snake called Katuka Rekula Poda in the local Telugu language, whose venom was shown experimentally by Dr Russell to be nearly as lethal as that of Cobra de Capello. The snake is now known as Vipera russelli or Russell's viper. Dr Russell was representative of the naturalistic tendency of British medicine in the late 18th century. He was a keen observer and skilled doctor in clinical practice, particularly in Aleppo, Syria, during an outbreak of the plague, and indefatigable in his study of plant and animal life both in Aleppo and later in the Madras Province of India. As a physician as well as Naturalist to the East India Company in the Carnatic he was concerned with the problem of snakebite. His first aim was to find a means whereby the non-specialist could distinguish between poisonous and harmless snakes and so combat the terrible notion that all bites were mortal. His writing, encompassing social and natural histories and climaxed by a study of snakes, has left a rich legacy. Dr Patrick Russell was a man of the highest integrity and ability, a physician and naturalist par excellence. PMID- 7886690 TI - Clinical implications of research on the box-jellyfish Chironex fleckeri. AB - Despite several decades of laboratory research, many anecdotal clinical publications and successful production of antivenom, the active components of Chironex fleckeri venom and their mechanisms of toxicity remain poorly elucidated. Conflicting results of animal experiments and venom studies and the lack of controlled clinical trials necessitate caution in formulating protocols of clinical management. Of particular note are that in severe envenomation (1) clinical deterioration can occur within minutes and cardiac support must be emphasised in addition to respiratory support; (2) larger doses of antivenom may be appropriate; and (3) recommendations of therapy with verapamil and other cardioactive drugs remain controversial. PMID- 7886691 TI - Development of an enzyme-linked immunosorbent assay (ELISA) for identification of venoms from snakes in the Agkistrodon genus. AB - An enzyme-linked immunosorbent assay (ELISA) using a purified myotoxin from the venom of Agkistrodon contortrix laticintus (broad-banded copperhead) as immunogen was developed for potential use in the identification of envenomation by snakes belonging to the genus Agkistrodon native to North America. The specificity of the assay was tested using a total of 43 venom samples from snakes of diverse geographic locations. Venom samples used for cross-reactivity determination represent eight snake families including 14 species from the genus Crotalus. The assay detected venom from all Agkistrodon species tested without significant cross-reactivity with other venoms except for samples from two species of Bothrops which do not occur naturally north of Southern Mexico. The detection limit of the assay was 2 ng/ml for homologous crude venom dissolved in normal human serum. The assay was highly accurate in correlating optical densities with venom concentrations (r = 0.997). The presence of the antigen in experimental envenomations was readily detected by the assay at an i.m. injection dosage of 0.1 microgram/g. This ELISA is a promising test for identification of envenomations by species of Agkistrodon found in most of North America. It can also be used to study the kinetics of the myotoxin in experimental envenomations. PMID- 7886692 TI - Immunochemical relatedness between secretory phospholipase A2 and intracellular phospholipase A2 activity linked with arachidonic acid mobilization in macrophages. AB - To determine whether low mol. wt phospholipase A2 (PLA2) is involved in the mechanism of arachidonic acid mobilization induced by zymosan in mouse peritoneal macrophages, we developed an immunoblot analysis and ELISA assay using the polyclonal antibodies anti-PLA2 type I and type II previously characterized. We also measured the effect of low mol. wt PLA2 inhibitors such as p-bromophenacyl bromide, aristolochic acid, nordihydroguaiaretic acid, all trans-retinal and all trans-retinoic acid on the action of these enzymes. The antibodies antitype I PLA2 bound to mouse platelet protein fraction, while the antibodies antitype I or antitype II did not recognize components of the macrophages. Furthermore, low mol. wt PLA2 inhibitors did not inhibit arachidonic acid release produced during the phagocytosis of zymosan. This suggests that low mol. wt PLA2 are not present in cells such as macrophages. These results are consistent with a role for high mol. wt PLA2 in arachidonic acid mobilization. PMID- 7886693 TI - Purification and characterization of L-amino acid oxidase from king cobra (Ophiophagus hannah) venom and its effects on human platelet aggregation. AB - Venoms of several snake species contain large amounts of L-amino acid oxidase but its effects on human plasma coagulation and platelet aggregation have not been explored. We have purified L-amino acid oxidase from king cobra venom through CM Sephadex C-25, Sephadex G-100 and DEAE Sephadex A-50 chromatographies. The purified enzyme has a mol. wt of 135,000 as determined by gel filtration and 65,000 by SDS-PAGE under non-reducing and reducing conditions. Incubation of plasma with L-amino acid oxidase at 200 micrograms/ml did not affect prothrombin time, activated partial thromboplastin time, or thrombin time. Upon addition of L amino acid oxidase, platelets in platelet-rich plasma were aggregated. The enzyme induced aggregation was abolished by catalase. The aggregation was also inhibited by indomethacin, aspirin, ethylenediaminetetraacetate, sodium nitroprusside, prostaglandin E1, mepacrine and verapamil, but not by heparin, hirudin, creatine phosphate/creatine phosphokinase or antimycin/2-deoxy-D-glucose. These results suggest that L-amino acid oxidase induces human platelet aggregation through the formation of H2O2, and subsequent thromboxane A2 synthesis requiring Ca2+ but independent of ADP release. The platelet aggregation caused by L-amino acid oxidase is likely to contribute to toxicity inflicted by cobra venom. PMID- 7886695 TI - Detection of ricin by colorimetric and chemiluminescence ELISA. AB - A highly sensitive and specific ELISA was developed to detect ricin in biological fluids. The assay utilizes an affinity-purified goat polyclonal antibody to adsorb ricin from solution. The same antibody (biotinylated) is then used to form a sandwich, and avidin-linked alkaline phosphatase allows color development and measurement of optical density at 405 nm. Our routine assay uses a standard curve over the range of 0-10 ng/ml ricin, with accurate quantitation below 1 ng/ml (100 pg/well) in assay buffer as well as in a 1:10 dilution of human urine or 1:50 dilution of human serum spiked with ricin. Ricin measured in spiked samples demonstrated accuracy typically within 5% of the expected value in all matrices. The coefficient of variation ranged from 3-10% at 10 ng/ml to 8-25% at 2.5 ng/ml. Two variations on the routine assay were also investigated. First, lengthened incubation times and additional time for color development allowed accurate quantitation in serum dilutions as low as 1:2. Second, increased concentrations of biotinylated antibody and avidin-linked enzyme from 1:250 to 1:70 enhanced the sensitivity of the assay 10-fold, achieving a detection limit of at least 100 pg/ml (10 pg/well). The assay was also configured to a format based upon chemiluminescence, which allowed quantitation in the 0.1-1 ng/ml range, but was subject to slightly greater variability than the colorimetric assay. PMID- 7886694 TI - Broad cytolytic specificity of myotoxin II, a lysine-49 phospholipase A2 of Bothrops asper snake venom. AB - The cytotoxic activity of Bothrops asper myotoxin II, a lysine-49 phospholipase A2 isoform, on different cell types in culture, was investigated. Myotoxin II caused a dose-dependent cytolytic effect on all cell types tested, characterized by rapid release of cytoplasmic lactic dehydrogenase and drastic morphological cell alterations. Quantitative differences in the susceptibility to myotoxin II among cell types fell within a relatively narrow range, and in general, the toxin was cytolytic at concentrations of 50-100 micrograms/ml (3-7 microM), when assays were performed using culture medium as a diluent. Toxin activity was markedly enhanced if phosphate-buffered saline was utilized instead of medium. The cytotoxic activity of myotoxin III, an aspartate-49 isoform from the same venom, on both endothelial cells and skeletal muscle myoblasts was higher than that of myotoxin II, suggesting that, although phospholipase A2 activity is clearly not required for the induction of cell damage, it may have an enhancing role. In contrast to B. asper myotoxins, other basic phospholipases A2 with myotoxic activity in vivo (notexin from Notechis scutatus, and two enzymes isolated from Vipera russelli venom) did not affect endothelial cells and myoblasts. Pretreatment of cells with neuraminidase, tunicamycin, or protamine, did not alter their susceptibility to myotoxin II. At low temperatures (2-4 degrees C) myotoxin II was devoid of cytolytic effect. Washing and neutralization experiments using heparin with low affinity for antithrombin or mouse monoclonal antibody MAb-3 suggest that at low temperatures myotoxin II binds very weakly to the cells, and that its normal interaction with the putative target is probably not only based on charge, but that a membrane penetration event may be required. PMID- 7886696 TI - Comparison of mouse bioassay, HPLC and enzyme immunoassay methods for determining diarrhetic shellfish poisoning toxins in mussels. AB - Mussel specimens (Mytilus galloprovincialis) collected from two different areas of the Adriatic Sea were analysed for diarrhoetic shellfish poisoning (DSP) toxin by three methods: mouse bioassay, the DSP Check enzyme immunoassay kit, and high performance liquid chromatography (HPLC). The results obtained confirm that Yasumoto's mouse bioassay, capable of detecting all the components of the DSP group, is still necessary to determine the wholesomeness of the product. The ELISA method has not always given quantitatively reliable results. The HPLC method is advantageous in terms of sensitivity, accuracy, specificity and rapidity. However, its application is limited so far to the determination of okadaic acid in mussels. PMID- 7886697 TI - Brevetoxin-3 (PbTx-3) inhibits oxygen consumption and increases Na+ content in mouse liver slices through a tetrodotoxin-sensitive pathway. AB - To have insights into possible non-neural effects of PbTx-3 (0.07 microgram/ml), its effects on various parameters of hepatic metabolism were evaluated. PbTx-3 inhibits oxygen consumption (QO2) in liver slices by 25 +/- 1%, and increases hepatocyte Na+/K+ ratio by 72 +/- 4%. Ouabain, a Na(+)-K(+)-pump inhibitor, also reduced QO2 by 19 +/- 2% and raised the Na+/K+ ratio by 77 +/- 4%. The effects of PbTx-3 and ouabain on QO2 and Na+/K+ ratio were not additive, suggesting a role for the Na(+)-K(+)-pump in these actions of PbTx-3. However, Na(+)-K(+)-pump activity determinations, using 86Rb as a K+ tracer, did not reveal inhibitory effects of this toxin on the transport system. This indicates that the pump is not a target of PbTx-3. The effect of PbTx-3 on liver slices Na+ content was abolished by the sodium channel blocker tetrodotoxin (0.1 microM). Tetrodotoxin also antagonized the inhibition of oxygen consumption by PbTx-3. These results suggest that in the liver PbTx-3 can induce effects that appear to be similar to those observed in excitable tissue. PMID- 7886698 TI - Aspects of the haemolytic reaction induced by Kanagawa haemolysin of Vibrio parahaemolyticus. AB - Vibrio parahaemolyticus, an important enteric pathogen, produces toxin (Kanagawa haemolysin, KH), the presence of which correlates well with pathogenicity. KH induced lysis of human red blood cells (HRBC); the kinetics were strongly dependent on KH concentration (0-1 HU/ml) and rather independent of target cell concentration [0.5 < or = haematocrit (%) < or = 6] and the ratio KH:HRBC. The suggestion that KH-induced haemolysis is due to colloid osmosis is supported by results indicating: (1) osmotic protection (by suspension in iso-osmotic choline chloride, D-sorbitol or L-valine, or MOPS-buffered saline with added sucrose), (2) a cell volume increase prior to lysis, and (3) an increase in HRBC cation (86Rb+) influx after KH addition, indicating raised passive cation permeation. The effect of temperature on KH-induced haemolysis indicates the importance of processes other than the action of a simple water-filled pore, because of the high activation energy [53.30 +/- 2.79 kJ (mol.)-1] involved. Although haemolytic rate was attenuated by washout after 5 min KH exposure, the KH-induced lesion itself was not susceptible to washout by either extracellular volume expansion (at constant osmolarity) or centrifugation/resuspension. This suggests that HRBC binding of KH from aqueous solution still continues after 5 min exposure at 37 degrees C. Pre-vortexing KH with dibutyl phthalate (DBP) dramatically reduced the haemolytic activity of the aqueous toxin preparation, suggesting a protein-lipid interaction, which may support the contention that KH can move from a hydrophilic to a hydrophobic environment. Two features were identified that are characteristic of highly purified TDH preparations: (1) thermostability of haemolysin, and (2) monovalent cation selectivity series of lesion: Cs+ > Li+ > K+ > Rb+ > Na+, confirming that TDH is the important leak-inducing agent of KH. PMID- 7886699 TI - Application of a monoclonal antibody to estimate rabbit fibrinopeptide A released by habutobin. AB - We reported previously that habutobin, one of the type A thrombin-like enzymes, releases fibrinopeptide A alone from rabbit fibrinogen. To evaluate the effective action of habutobin in experiments using rabbit for the treatment of thrombosis, we attempted to develop an immunological method for measuring the fibrinopeptide A level in the circulating blood of rabbit. The purified rabbit fibrinopeptide A was coupled to keyhole limpet hemocyanin and BALB/c mice were immunized with the resultant fibrinopeptide A-hemocyanin conjugate. The spleen cells of an immunized mouse were fused with myeloma cells (P3-X63-Ag8-U1). As a result, one hybridoma (a-F-7) was selected, which secreted an antibody against rabbit fibrinopeptide A. Using this monoclonal antibody, we developed a competitive enzyme-linked immunoassay for estimating rabbit fibrinopeptide A. It was able to measure rabbit fibrinopeptide A contained in bentonite defibrinated plasma. This competitive enzyme-linked immunoassay should be useful for determining the fibrinopeptide A level in the circulating blood of rabbits, using plasma defibrinated by bentonite. PMID- 7886700 TI - Edematogenic responses induced by Bothrops jararaca venom in rats: role of lymphocytes. AB - The intraplantar injection of Bothrops jararaca venom (Bjv) caused an edematogenic response in the rat which was of rapid onset, and reached a peak in about 60 min. The response was markedly attenuated in animals rendered leucopenic by the administration of amethopterin. This inhibition was partially reverted when leucopenic rats were given i.v. suspensions of lymphocytes. Suspensions of neutrophils were ineffective. If the animals were submitted to an experimental obstruction of the thoracic duct, which leads to specific lymphocytopenia, similar inhibition of the edematogenic response was observed. These results suggest that lymphocytes can directly influence the development of the edema induced by Bothrops jararaca venom. PMID- 7886701 TI - Tissue distribution of human acetylcholinesterase and butyrylcholinesterase messenger RNA. AB - Cholinesterase inhibitors occur naturally in the calabar bean (eserine), green potatoes (solanine), insect-resistant crab apples, the coca plant (cocaine) and snake venom (fasciculin). There are also synthetic cholinesterase inhibitors, for example man-made insecticides. These inhibitors inactivate acetylcholinesterase and butyrylcholinesterase as well as other targets. From a study of the tissue distribution of acetylcholinesterase and butyrylcholinesterase mRNA by Northern blot analysis, we have found the highest levels of butyrylcholinesterase mRNA in the liver and lungs, tissues known as the principal detoxication sites of the human body. These results indicate that butyrylcholinesterase may be a first line of defense against poisons that are eaten or inhaled. PMID- 7886702 TI - Characterization of the antihemorrhagic factors of mongoose (Herpestes edwardsii). AB - Three antihemorrhagic factors (AHF1, AHF2 and AHF3) isolated from the serum of mongoose (Herpestes edwardsii) are glycoproteins of monomer structure with the same mol. wt (about 65,000), which contain 4.2%, 13.6% and 6.0% carbohydrates as glucose, respectively. All are composed of about 600 amino acids of similar composition. The 32 amino terminal amino acid sequences of three antihemorrhagic factors were determined, and sequence homologies were examined. AHF1 and AHF2 were of the same amino acid sequence, and showed high homologies to AHF3, oprin (opossum proteinase inhibitor) and human alpha 1B-glycoprotein; 68.7%, 42.3% and 50.0% identity, respectively. AHF1 completely inhibited the hemorrhagic activity of HR2b, the hemorrhagic factor of habu snake, at the concentration of five-fold molar excess, although incomplete inhibition (50%) of proteinase activity of the hemorrhagic factor was observed even at the concentration of 20-fold molar excess of antihemorrhagic factor. Incubation of HR2b with AHF1, and analysis of the reaction products by chromatography on TSK gel G-3000SW and on the ultracentrifuge did not show formation of an inactive enzyme inhibitor complex. However, the complex formation between AHF1 and HR2b was observed by a BIAcore analysis and TSK gel SP-5PW column chromatography. No alteration in the primary or the secondary structure of both factors was demonstrated by SDS-PAGE and circular dichroism spectrum at the far-UV wavelength before and after incubation of both factors, respectively. PMID- 7886703 TI - The amino acid sequences of two postsynaptic neurotoxins isolated from Malayan cobra (Naja naja sputatrix) venom. AB - The complete amino acid sequences of two postsynaptic neurotoxins (toxin-3 and toxin-5) isolated from Malayan cobra (Naja naja sputatrix) venom were determined by direct automated Edman degradation of peptides obtained from digests with various proteases. Toxin-3 and toxin-5 are both short-chain neurotoxins and their amino acid sequences are highly homologous to Naja naja atra and Naja naja philippinensis neurotoxin, respectively. Toxin-3 is unique in possessing aspartic acid (D) as the fifth residue, while all other homologous short-chain neurotoxins have asparagine (N) at the corresponding position. PMID- 7886704 TI - Addition-order dependent modulation of the sensitivity of rabbit erythrocyte membrane to bee venom phospholipase A2 by oleic acid, lysophosphatidyl choline and albumin. AB - The addition of exogenous oleic acid to erythrocyte membranes induces a characteristic membrane crenation and sensitises the cells to the lytic action of phospholipase A2 enzymes. Both effects are extremely sensitive to inhibition by endogenous lysophosphatidyl choline (LPC), but the strength of inhibition depends of the order in which the reagents are added to the cells. These responses are further enhanced when the reagents are extracted from the cell membranes by treatment with albumin. Thus the inhibitory action of LPC added before oleic acid increases when the reagents have been extracted but that of LPC added after oleic acid decreases after extraction. The results are discussed in terms of the stimulation of PLA2 activity by enhanced membrane curvature. PMID- 7886705 TI - Bibliography of toxinology. PMID- 7886706 TI - Multinational comparisons of stroke epidemiology. Evaluation of case ascertainment in the WHO MONICA Stroke Study. World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease. AB - BACKGROUND AND PURPOSE: As part of the WHO MONICA Project (World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease), mortality and incidence rates of acute stroke in 14 centers covering 21 populations from 11 countries were compared. METHODS: In this report, coverage and quality of the MONICA stroke registers were evaluated on five key indicators using data submitted to the MONICA Data Center. RESULTS: A low ratio of MONICA stroke register to routine statistics of stroke mortality and a low proportion of nonfatal out-of-hospital events were the most common biases; they indicate that identifications of fatal cases and/or case finding of nonfatal events occurring outside the hospital were inadequate in many MONICA centers. In 10 populations, the data quality analyses suggested that clarification of possible biases would be needed before these populations can be included in a comparative study. Data from the remaining 11 populations meet the data quality standards for multinational comparisons with respect to case ascertainment. CONCLUSIONS: These results show that multinational comparisons of stroke incidence involve considerable problems in developing and maintaining appropriate standards of data quality. However, after considerable efforts to ensure quality, comparisons of stroke data within the MONICA Project are possible among a large number of the MONICA populations. Our observations also indicate that results from multinational comparisons of stroke mortality based on routine statistics must be interpreted with caution. PMID- 7886707 TI - Stroke incidence, case fatality, and mortality in the WHO MONICA project. World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease. AB - BACKGROUND AND PURPOSE: This report compares stroke incidence, case fatality, and mortality rates during the first years of the WHO MONICA Project in 16 European and 2 Asian populations. METHODS: In the stroke component of the WHO MONICA Project, stroke registers were established with uniform and standardized rules for case ascertainment and validation of events. RESULTS: A total of 13,597 stroke events were registered from 1985 through 1987 in a total background population of 2.9 million people aged 35 to 64 years. Age-standardized stroke incidence rates per 100,000 varied from 101 to 285 in men and from 47 to 198 in women. The combined stroke attack rates for first and recurrent events were approximately 20% higher than incidence rates in most populations and varied to the same extent. Stroke incidence rates were very high among the population of Finnish men tested. The incidence of stroke was, in general, higher among populations in eastern than in western Europe. It was also relatively high in the Chinese population studied, particularly among women. The case-fatality rates at 28 days varied from 15% to 49% among men and from 18% to 57% among women. In half of the populations studied, there were only minor differences between official stroke mortality rates and rates measured on the basis of fatal events registered and validated for the WHO MONICA stroke study. CONCLUSIONS: The WHO MONICA Project provides a unique opportunity to perform cross-sectional and longitudinal comparisons of stroke epidemiology in many populations. The present data show how large differences in stroke incidence and case-fatality rates contribute to the more than threefold differences in stroke mortality rates among populations. PMID- 7886708 TI - The impact of alcohol and hypertension on stroke incidence in a general Japanese population. The Hisayama Study. AB - BACKGROUND AND PURPOSE: The relationship between alcohol intake and stroke has been inconsistent in previous studies. We examined the separate and combined effects of drinking habits and hypertension on stroke incidence in a prospective survey of a general Japanese population. METHODS: A total of 1621 stroke-free Hisayama residents aged 40 years or older were classified by their alcohol intake into nondrinkers, light drinkers (< 34 g of ethanol per day), and heavy drinkers (> or = 34 g of ethanol per day) and followed up prospectively for 26 years from 1961. RESULTS: During the follow-up period, cerebral infarction developed in 244 subjects and cerebral hemorrhage in 60. For men, the incidence of cerebral hemorrhage increased significantly with rising alcohol consumption. In contrast, the incidence of cerebral infarction was slightly lower in light drinkers than in nondrinkers, while it increased significantly in heavy drinkers compared with light drinkers. Female drinkers had a lower incidence of cerebral infarction but a slightly higher incidence of cerebral hemorrhage than nondrinkers, as did male light drinkers. Among the hypertensive subjects, the age- and sex-adjusted relative risk of cerebral hemorrhage was significantly elevated in heavy drinkers versus abstainers (3.13; 95% confidence interval [CI], 1.08 to 9.10), but the increase was not significant for light drinkers. In contrast, the relative risk did not significantly increase for normotensive light and heavy drinkers. Compared with hypertensive light drinkers, the relative risk of cerebral infarction significantly increased in hypertensive heavy drinkers (1.96; 95% CI, 1.08 to 3.57) but remained unchanged in normotensive heavy drinkers. Significant associations between alcohol intake and stroke were substantially the same even after controlling for other risk factors in multivariate analysis. CONCLUSIONS: Among hypertensive individuals, heavy alcohol consumption leads to a significant increase in the risk of cerebral hemorrhage, suggesting a synergistic effect of alcohol and hypertension, while light alcohol consumption significantly reduces the risk of cerebral infarction. PMID- 7886709 TI - Recent infection as a risk factor for cerebrovascular ischemia. AB - BACKGROUND AND PURPOSE: Previous infection is discussed as a risk factor for ischemic stroke in children and younger adults. We tested the hypothesis that the role of recent infection in cerebrovascular ischemia is not restricted to younger patients and investigated which infections are mainly relevant in this respect. METHODS: We performed a case-control study with 197 patients aged 18 to 80 years with acute cerebrovascular ischemia and 197 randomly selected control subjects matched for sex, age, and area of residence. RESULTS: Infection within 1 week before ictus or examination was significantly more common among patients (38 of 197) than control subjects (10 of 197; odds ratio [OR], 4.5; 95% confidence interval [CI], 2.1 to 9.7). Patients more often had febrile and subfebrile infections (> or = 37.5 degrees C) than control subjects (29 of 197 versus 5 of 197; OR, 7.0; 95% CI, 2.5 to 20). Respiratory tract infections were most common in both groups. Bacterial infections dominated among patients but not among control subjects. Infection increased the risk for cerebrovascular ischemia in all age groups; this reached significance for patients aged 51 to 60 and 61 to 70 years. The profile of vascular risk factors was similar in patients with and patients without previous infection. Infection remained a significant risk factor when previous stroke, hypertension, diabetes mellitus, coronary heart disease, and current smoking were included as covariates in a logistic model (OR, 4.6; 95% CI, 1.9 to 11.3). CONCLUSIONS: Recent infection, primarily of bacterial origin, may be a risk factor for cerebrovascular ischemia in older as well as younger patients. PMID- 7886710 TI - Silent cerebral infarction in a community-based autopsy series in Japan. The Hisayama Study. AB - BACKGROUND AND PURPOSE: The purpose of this study was to assess the prevalence and characteristics of silent cerebral infarction in a population-based consecutive autopsy series of residents of Hisayama, Kyushu, Japan. METHODS: Autopsy records, cerebral pathological findings, and clinical charts of 966 Hisayama residents recorded during the 26 years from 1961 to 1987 were examined (autopsy rate, 82.4%). The subjects were divided into three groups: those with both clinically apparent strokes and pathologically verified cerebral infarcts (stroke group), those having pathological evidence of cerebral infarction in the brain but without clinical stroke episodes (silent infarction group), and those with neither infarction nor stroke episode (noninfarction group). Risk factors and brain pathology in the three groups were compared. RESULTS: Silent cerebral infarction was found in 12.9% of the 966 subjects who had undergone autopsy, and its frequency increased with age. The subjects with silent infarcts were older, had higher systolic or diastolic blood pressure, and had atrial fibrillation more frequently than subjects in the noninfarction group. There were no significant differences in the locations of infarcts between the stroke and silent infarction groups, although infarcts tended to be located in the deeper area of the brain in the latter. The number and size of infarcts were smaller in the silent infarction group than in the stroke group. CONCLUSIONS: Diastolic blood pressure and atrial fibrillation appear to be strong predictors of silent cerebral infarction in the Japanese general population. Stroke becomes clinically apparent as infarct volume increases. PMID- 7886711 TI - Arterial wall thickness is associated with prevalent cardiovascular disease in middle-aged adults. The Atherosclerosis Risk in Communities (ARIC) Study. AB - BACKGROUND AND PURPOSE: This study was done to assess the relationship between prevalent cardiovascular disease and arterial wall thickness in middle-aged US adults. METHODS: The association of preexisting coronary heart disease, cerebrovascular disease, and peripheral vascular disease with carotid and popliteal intimal-medial thickness (IMT) (measured by B-mode ultrasound) was assessed in 13,870 black and white men and women, aged 45 to 64, during the Atherosclerosis Risk in Communities (ARIC) Study baseline examination (1987 through 1989). Prevalent disease was determined according to both participant self-report and measurements at the baseline examination (including electrocardiogram, fasting blood glucose, and medication use). RESULTS: Across four race and gender strata, mean carotid far wall IMT was consistently greater in participants with prevalent clinical cardiovascular disease than in disease free subjects. Similarly, the prevalence of cardiovascular disease was consistently greater in participants with progressively thicker IMT. The greatest differences in carotid IMT associated with prevalent disease were observed for reported symptomatic peripheral vascular disease (0.09 to 0.22 mm greater IMT in the four race-gender groups). CONCLUSIONS: These data document the substantially greater arterial wall thickness observed in middle-aged adults with prevalent cardiovascular disease. Both carotid and popliteal arterial IMT were related to clinically manifest cardiovascular disease affecting distant vascular beds, such as the cerebral, peripheral, and coronary artery vascular beds. PMID- 7886712 TI - Early predictors of death and disability after acute cerebral ischemic event. AB - BACKGROUND AND PURPOSE: Many clinical trials are currently being conducted to evaluate the ability of neuroprotectors and thrombolytic agents to improve survival and functional outcome after ischemic stroke. Such trials require early predictors of survival and disability for ethical and methodological reasons. The aim of the study was to determine which variables, of those easily assessable during the first 24 hours after stroke onset, would be predictors of 8-day mortality rate and 3-month clinical outcome. METHODS: One hundred fifty-two consecutive patients with an acute ischemic event were evaluated within 24 hours after symptom onset. We determined (1) the 8-day mortality rate and (2) the 3 month functional outcome (Glasgow Outcome Scale). The following potential predictors of outcome were tested by means of a stepwise logistic regression analysis: age, sex, body mass index, atrial fibrillation, previous stroke, existence of headache, Orgogozo score, level of consciousness, swallowing disturbances, hemianopia, pulse rate, mean blood pressure, hematocrit, glycemia, and computed tomographic scan data (cerebral atrophy score, hyperdense middle cerebral artery sign, number of silent infarcts, leukoaraiosis score). RESULTS: The multivariate analysis revealed that the 8-day mortality rate depended only on the level of consciousness at admission (P = .0001); death or dependence at month 3 (scores 3 to 5 on the Glasgow Outcome Scale) depended on the severity of the clinical deficits (P = .0001), previous stroke (P = .0018), and age (P = .0237). CONCLUSIONS: In future drug trials, the distribution of patients between "active treatment" and "placebo" groups should be balanced regarding the severity of clinical deficits, history of stroke, and age. PMID- 7886713 TI - Return to work after stroke. A follow-up study. AB - BACKGROUND AND PURPOSE: Few studies have reported the longitudinal trend of return to work after stroke. The purpose of our study was to evaluate the longitudinal trend of proportion of patients who return to work after stroke and further to examine the predictors of return to work while taking follow-up periods into consideration. METHODS: We conducted a retrospective cohort study on the association between characteristics of stroke patients at admission and return to work after first stroke, taking length of follow-up period into consideration (n = 183). The patients were all younger than 65 years and were working at the time of their stroke. A follow-up questionnaire evaluated return to work and related information. Data were analyzed using the Kaplan-Meier method for curves of the proportion of return to work and Cox's proportional hazards model for odds ratios of return to work. RESULTS: The curve of proportion of return to work had two steep slopes, and the proportion was at a maximum at 18 months from patient admission. The adjusted odds ratios of return to work for patients with normal muscle strength versus severe weakness, without apraxia versus with apraxia, and with white-collar versus blue-collar occupations were 5.16 (P < .05), 4.16 (P < .05), and 1.43 (.05 < P < .10), respectively. CONCLUSIONS: The increase of proportion of return to work after stroke was nonlinear, and this trend was referable to the social security systems available to the patients included in this study. Normal muscle strength and absence of apraxia were significant predictors of return to work after stroke. White-collar occupation showed a tendency to promote return to work. PMID- 7886714 TI - Quality of life after stroke. Impact of stroke type and lesion location. AB - BACKGROUND AND PURPOSE: Little attention has been focused on the relationship between neurological lesions and quality of life (QL) in stroke research. The purpose of this study was to analyze the impact of stroke types and lesion locations on QL. METHODS: The study sample was composed of 441 stroke patients. Lesion locations and stroke types were divided into 194 left-sided and 173 right sided lesions, 61 infratentorial strokes (55 infarctions and 6 hemorrhages), and 335 supratentorial strokes (204 [sub]cortical infarctions, 82 lacunar infarctions, and 49 hemorrhages). Six months after stroke, QL was assessed with the Sickness Impact Profile. Age-adjusted QL scores were expressed in standard scores. RESULTS: Although patients with left-sided lesions had more speech pathology (P < .001), there was slightly more QL deterioration in patients with right-sided lesions. Patients with infratentorial strokes reported better overall functioning than patients with supratentorial strokes (P = .02). Patients with lacunar infarction had less dysfunction compared to patients with (sub)cortical lesions (P < .001). There was no difference in QL between supratentorial (sub)cortical infarcts and hemorrhages. Lesion locations and stroke types did not affect patients' emotional distress. Severely impaired QL patterns were related significantly to older age (P < .001), comorbidity (P = .02), stroke severity (P < .001), and supratentorial lesions (P = .02). CONCLUSIONS: There is only a weak relationship between lesion laterality and QL. Survivors of hemorrhagic strokes do not evidence more QL impairment than survivors of ischemic strokes. Stroke per se is not unequivocally followed by emotional discomfort. In addition to stroke type, patient and clinical characteristics are also important in explaining impaired QL patterns. PMID- 7886715 TI - Current emergency department management of stroke in Houston, Texas. AB - BACKGROUND AND PURPOSE: This study describes emergency department (ED) management of stroke in Houston, Tex, in 1992 to identify delays and deficiencies in recognition and management of stroke patients in various hospital subtypes and to quantitate the impact of a rapid response stroke team. METHODS: ED logs of eight hospitals were retrospectively screened, and 112 patients with suspected acute stroke onset within 6 hours were identified. EDs were divided into four groups based on hospital size (175 to 979 beds), acuity, number of stroke admissions (50/y to 210/y), and availability of neurological consultations. The intervals from stroke onset to triage, examination by a physician, neurological evaluation, computed tomography (CT) and other tests, vital signs, and treatments were recorded. RESULTS: The average time from stroke to ED arrival was 115 minutes, and times from ED arrival to examination by a physician and CT scan were 28 and 100 minutes, respectively, with little variability among hospital groups except that the public hospital was slower. Neurological examinations were poorly documented in community and public hospitals. The presence of a stroke team shortened the time to examination by a physician and to CT by 13 and 63 minutes, respectively, and increased the number of patients admitted to the intensive care unit. Blood pressure was excessively lowered in 31% of hypertensive patients, and hypotonic dextrose intravenous fluids were given to 69% of all patients. CONCLUSIONS: Transport, initial evaluation, and ED care of acute stroke patients are currently slow and often inexpert in all types of hospitals. A stroke team can speed initial ED management. PMID- 7886716 TI - Human leukocyte antigen in patients with moyamoya disease. AB - BACKGROUND AND PURPOSE: Progressive stenosis or occlusion of bilateral internal carotid arteries by fibrocellular intimal thickening results in cerebral ischemia in moyamoya disease. In an attempt to elucidate the still-unknown etiologic factors in moyamoya disease, we assessed human leukocyte antigens in patients with this disease. METHODS: We investigated 32 unrelated Japanese patients with moyamoya disease for typing of human leukocyte antigen A, B, C, and DR/DQ and compared the results with those from 178 unrelated control subjects. RESULTS: We found a significant association of human leukocyte antigen B51 with moyamoya disease (corrected P < .05, chi 2 test). Although no significant associations were observed in DR/DQ typing, the frequency of the B51-DR4 combination was significantly higher in moyamoya patients than in control subjects (P < .002, Fisher's exact test). CONCLUSIONS: These findings suggest that there may be a genetic predisposition for moyamoya disease and that host factors may play a role in the development of intimal thickening in early childhood. PMID- 7886717 TI - Carotid diameter and blood flow velocities in cerebral circulation in hypertensive patients. AB - BACKGROUND AND PURPOSE: The recent development of noninvasive techniques for the evaluation of the carotid arteries has focused attention on the study of arterial wall thickness to identify early lesions of vessels in patients at high risk for atherosclerosis, such as those with hypercholesterolemia, diabetes mellitus, and hypertension. METHODS: In a sample of 70 hypertensive patients without clinical evidence of target organ damage, we showed a thickening of the intimal plus medial layers compared with age- and sex-matched normotensive control subjects. In this sample we also studied the diameter of the carotid arteries by ultrasound imaging, and we studied flow velocities in common carotid, internal carotid, and middle cerebral arteries by Doppler technique. Pulsatility and resistance indexes were calculated. RESULTS: Absolute values of the carotid diameter were similar in the two groups (6.3 +/- 0.7 versus 6.0 +/- 0.8 mm); however, the ratio of diameter to blood pressure was significantly reduced in hypertensive compared with normotensive subjects (5.3 +/- 0.7 versus 6.5 +/- 0.8; P < .001 for mean blood pressure). Parietal stress was increased in the hypertensive subgroup and significantly correlated with arterial diameter in the normotensive group but not in the hypertensive group. No significant differences between the two groups were observed in blood flow velocities, with the exception of a slight significant increase of mean velocity in the internal carotid artery in hypertensive patients (37.5 +/- 9.1 versus 32.7 +/- 3.0 cm/s; P < .02). CONCLUSIONS: These results indicate that in addition to the degenerative changes of the common carotid wall, the diameter of the carotid artery and the relation to parietal stress show an early impairment in patients with uncomplicated hypertension. PMID- 7886718 TI - Stroke patterns in unilateral atherothrombotic occlusion of the internal carotid artery. AB - BACKGROUND AND PURPOSE: Stroke patterns in patients with occlusion of the internal carotid artery (ICA) and no potential cardiac cause of stroke remain unknown. The aim of our study was to determine the pattern of stroke in patients with an occlusion of the ICA of presumed atherosclerotic origin. METHODS: Of 873 consecutive patients admitted for an acute ischemic event during a 49-month period, 40 (29 men and 11 women; mean age, 63 years) had a unilateral occlusion of the ICA of presumed atherosclerotic origin and no other potential cause of stroke. They underwent two computed tomographic scans, Doppler ultrasonography, and B-mode echotomography of the cervical arteries or angiography and echocardiography. We compared stroke patterns between both hemispheres. RESULTS: We found ipsilateral infarcts in 32 patients (80%; 99% confidence interval [CI], 64% to 96%) and contralateral infarcts in 12 patients (30%; 99% CI, 11% to 49%). Infarcts ipsilateral to the ICA occlusion were more likely to be cortical (odds ratio, 9.33; 99% CI, 2.4 to 36.35) or subcortical infarcts 15 mm or greater (odds ratio, 16.71; 99% CI, 1.05 to 267.3). The prevalence of subcortical infarcts less than 15 mm did not differ between hemispheres. CONCLUSIONS: Symptomatic infarcts related to an ICA occlusion are more likely to be cortical or large subcortical infarcts. Small subcortical infarcts have the same prevalence in both hemispheres and therefore may be coincidental. PMID- 7886719 TI - Pain-related and electrically stimulated somatosensory evoked potentials in patients with stroke. AB - BACKGROUND AND PURPOSE: Pain-related somatosensory evoked potentials (SEPs) were applied to study abnormality of pain sensation in stroke, together with electrically stimulated SEPs for deep sensation. METHODS: We recorded pain related SEPs after CO2 laser stimulation to the dorsum of the hand and electrically stimulated SEPs after median nerve stimulation at the wrist in 12 patients with stroke. We analyzed P340 in pain-related and parietal N20 in electrically stimulated SEPs. RESULTS: In 5 patients with a putaminal lesion, P340 was absent or its latency was delayed, and N20 was absent or reduced in amplitude. In 3 patients with a thalamic lesion, P340 and N20 showed various patterns according to the involved sites. In 4 patients with a lesion in the corona radiata, P340 and N20 were normal. CONCLUSIONS: Abnormalities of P340 and N20 in the stroke location were related to impairment of the pain and vibration senses, respectively. Thus, pain-related and electrically stimulated SEPs were useful to investigate the sensory function of each structure in the central nervous system in patients with stroke. PMID- 7886720 TI - Spontaneous middle cerebral artery reperfusion in ischemic stroke. A follow-up study with transcranial Doppler. AB - BACKGROUND AND PURPOSE: The aim of this study was to investigate by means of transcranial Doppler (TCD) ultrasonography how many spontaneous reperfusions of the middle cerebral artery (MCA) occurred during the first week after onset of acute ischemic stroke in the carotid territory. METHODS: TCD examination, computed tomographic scan, and arterial digital angiography were performed in 56 patients with acute ischemic stroke within 6 hours of the onset of symptoms. The TCD examination was repeated within 24 hours, 48 hours, and 7 days after stroke; a further TCD examination was performed within 3 to 9 months in 27 patients. RESULTS: At 6 hours, 33 patients presented abnormal TCD findings in the symptomatic MCA (16 "no flows" and 17 asymmetries). Of these, 4 patients (3 no flows and 1 asymmetry) died before the 7-day follow-up was completed, whereas of the 29 remaining patients undergoing all the TCD control examinations, only 14 presented permanently abnormal TCD findings (7 asymmetries and 7 no flows). These data are consistent with an MCA reperfusion occurring at any level of the MCA, although most frequently in the distal part, and in the majority of cases during the first 48 hours. One patient who showed MCA asymmetrical flow velocity at the day-7 TCD examination was normal at the TCD follow-up at 3 to 9 months. CONCLUSIONS: TCD examination offers an easy and reliable way of monitoring MCA reopening and might be useful to identify subgroups of patients who may benefit most from pharmacological reperfusion. PMID- 7886721 TI - Distinguishing carotid artery pseudo-occlusion with color-flow Doppler. AB - BACKGROUND AND PURPOSE: This study was undertaken to determine the impact of color-flow Doppler on the accuracy of noninvasive carotid imaging for distinguishing an internal carotid artery pseudo-occlusion (string sign) from a complete occlusion. METHODS: From January 1985 to January 1994, review of noninvasive vascular studies, arteriograms, and operative reports of 26 consecutive patients undergoing 27 carotid endarterectomies for carotid pseudo occlusion was performed. Further review was conducted of all patients identified with carotid occlusion by noninvasive testing who underwent confirmatory arteriography during the same interval. RESULTS: Conventional gray-scale duplex scanning (January 1985 to December 1989) correctly identified 3 of 11 (27%) pseudo-occluded internal carotid arteries compared with 15 of 16 (94%) internal carotid artery pseudo-occlusions correctly identified by color-flow Doppler (January 1990 to June 1994) (P < .01). Similarly, carotid occlusion was more accurately identified by color-flow Doppler (33 of 33, 100%) compared with gray scale duplex scanning (19 of 27, 90%) (P < .01). CONCLUSIONS: The addition of color-flow Doppler to the duplex evaluation of the extracranial carotid circulation improves the accuracy of distinguishing carotid pseudo-occlusion from the occluded internal carotid artery and may obviate the need for arteriography to identify patients with this critical level of carotid stenosis. PMID- 7886722 TI - Variability of Doppler microembolic signal counts in patients with prosthetic cardiac valves. AB - BACKGROUND AND PURPOSE: The purpose of this study was the evaluation of intraobserver, interobserver, and intrasubject variability in the Doppler detection of microembolic signals in patients with mechanical prosthetic valves. Simultaneously, the feasibility of automated embolus detection by means of a neuronal network was investigated. METHODS: From 25 patients with mechanical prosthetic heart valves, single transcranial Doppler monitoring sessions of 30 minutes' duration were recorded on videotape, randomized, and subsequently analyzed by eight independent trained observers from three centers. Three observers evaluated these tapes on three separate occasions, blinded to their previous results. An additional 48 patients with prosthetic heart valves were repetitively monitored with transcranial Doppler ultrasonography for 30 minutes three times within 1 year to examine the long-term variability in the occurrence of microembolic signals. Finally, in an effort to assess the short-term intrasubject variability, 20 patients were examined for 90 minutes, and the results of the three 30-minute periods were compared. The interobserver, intraobserver, and intrasubject (both short- and long-term) variability was evaluated. RESULTS: No significant differences in microembolic signal counts were found among the different observers, between the human observers and the neuronal network, or among the three separate evaluations of stored data by the same observer. The same was true for repeat examinations of the same patient (P > .05, Student's two-paired t test and Friedman's test). CONCLUSIONS: The detection of microembolic signals in patients with prosthetic cardiac valves is a reproducible technique. The reliable performance of the neuronal network argues for a broader use of this device. The intrasubject stability of the microembolic rate over 1 year supports the concept that the underlying emboligenic process is associated with intrinsic mechanical properties of the valve implant and not due to a thromboembolic process in the heart. PMID- 7886723 TI - A photothrombotic 'ring' model of rat stroke-in-evolution displaying putative penumbral inversion. AB - BACKGROUND AND PURPOSE: To facilitate reproducible and rigorous study of a tissue zone at risk of encroaching ischemic damage, we propose a new model in which the potentially compromised tissue lies within rather than perifocal to an ischemic locus. The perimeter of the "zone at risk" is defined by a photothrombotically produced cortical lesion in the shape of a toroid (or "ring"). METHODS: The exposed crania of erythrosin B-injected rats were irradiated with a 514.5-nm laser beam, configured as a 5-mm-diameter ring, to yield a ring-shaped lesion caused by photochemically induced platelet occlusion of cortical vasculature. Developing perfusion deficits in the interior region were revealed by carbon black infusion. Tissue damage and infarct volumes were assessed by light and electron microscopy, and blood-brain barrier integrity was assessed with Evans blue dye and horseradish peroxidase as tracers. RESULTS: For rats injected with 17 mg/kg erythrosin B and irradiated for 2 minutes with a ring beam intensity of 0.92 W/cm2 (beam power of 65 mW), carbon black infusion at times up to 4 hours demonstrated a shallow cortical ring lesion encircling a fully patent zone at risk, which by 24 hours evinced an essentially complete perfusion deficit. At times up to 24 hours, the ring lesion was penetrated at the pial surface by distal branches of the middle cerebral and anterior cerebral arteries. Stereotaxically based histopathological assessment showed that by 24 hours the lesion spanned the cortical thickness. Lesion volume increased from 14.5 +/- 8.0 mm3 (mean +/- SD) (n = 8) to 46.2 +/- 15.6 mm3 (n = 8) between 4 and 24 hours after irradiation (P < .01), but the anteroposterior lesion diameter did not change significantly between 4 hours (6.00 +/- 1.03 mm; n = 9) and 24 hours (6.75 +/- 1.15 mm; n = 9). CONCLUSIONS: The present model of slowly developing but inevitable cortical tissue death in a sequestered area should facilitate more precise observations of the evolution of tissue metabolic responses, from the impending onset of ischemia to the threshold of irreversible damage. This system may prove efficient for evaluating treatments intended to salvage a penumbral region. PMID- 7886724 TI - Combined perfusion and diffusion-weighted magnetic resonance imaging in a rat model of reversible middle cerebral artery occlusion. AB - BACKGROUND AND PURPOSE: Diffusion-weighted imaging and dynamic first-pass bolus tracking of susceptibility contrast agents (perfusion imaging) are two new magnetic resonance imaging techniques that offer the possibility of early diagnosis of stroke. The present study was performed to evaluate the diagnostic information derived from these two methods in a rat model of temporary focal ischemia. METHODS: Fifteen male Wistar rats were assigned to 45 (n = 7) or 120 minutes (n = 8) of middle cerebral artery occlusion followed by reperfusion using the intraluminal filament technique. The diffusion-weighted images were collected, and areas of hyperintensity were compared with histologically assessed areas of ischemic injury. The magnetic resonance perfusion image series were postprocessed to produce topographic 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: Hyperintensity in diffusion-weighted images was demonstrated after 30 minutes of middle cerebral artery occlusion and was mainly expressed in the lateral caudoputamen and parts of the lower frontoparietal cortex. Reperfusion after 45 minutes of occlusion reduced the area of hyperintensity from 24.2% to 9.9% of hemispheric area. In the group with 120 minutes of occlusion, the hyperintense area increased from 24.4% to 29.1%. Relative to the nonischemic hemisphere, the changes in the topographic maps of maximum signal reduction occurred in the lateral caudoputamen and adjacent lower neocortical areas. Increased time delay to maximum effect, however, was seen also in the upper frontoparietal cortex. CONCLUSIONS: Hyperintensity in diffusion-weighted images was reversible after 45 minutes but not after 120 minutes of middle cerebral artery occlusion. Analysis of the signal-reduction and time-delay parametric maps demonstrated regions of different perfusion changes in the ischemic hemisphere. PMID- 7886725 TI - Insular lesion evokes autonomic effects of stroke in normotensive and hypertensive rats. AB - BACKGROUND AND PURPOSE: Increases in sympathetic activity and frequency of myocardial damage occur after middle cerebral artery occlusion (MCAO) in Wistar rats, while MCAO in the spontaneously hypertensive rat (SHR) decreases sympathoadrenal activity. Autonomic changes have been suggested to result from damage to the insular cortex (IC). METHODS: A lesion of the IC was made using the excitotoxin D,L-homocysteic acid (DLH; 1 mol/L), in urethane-anesthetized Wistar rats and SHRs. Mean arterial pressure (MAP), heart rate, renal sympathetic nerve discharge (SND), ECG, and plasma catecholamines were measured in 14 SHRs and 14 Wistar male rats after a 500-nL injection of DLH or phosphate-buffered saline (PBS) into the IC. RESULTS: Histological examination showed that DLH resulted in neuronal damage throughout the IC. DLH injection initially elevated MAP (at approximately 10 minutes after injection) in Wistar rats but not in SHRs. At 4 hours after the DLH injection, there was a secondary, longer-term increase in MAP in the Wistar rats. MAP decreased in the SHRs after IC lesion such that at 6 hours, lesioned SHRs had a MAP that was significantly lower than that of sham lesioned SHRs. SND initially increased (at 10 minutes) after DLH injection in Wistar rats. In the SHRs, SND decreased significantly from the initial values, by 3 hours after DLH injection. Plasma catecholamine levels were not significantly changed as a result of IC lesion in the Wistar rats or the SHRs. Heart rates increased in all animals, with no differences between groups. There were no changes in the ECG or in the frequency of cardiac myocytolysis in either strain (sham or lesioned animals). CONCLUSIONS: IC lesion in the SHR and Wistar rat therefore appears to result in autonomic changes similar to that seen after MCAO. Unlike MCAO, however, the autonomic changes do not appear to be sufficient to produce myocardial damage. PMID- 7886726 TI - Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia. AB - BACKGROUND AND PURPOSE: Elevated glutamate levels are thought to be a primary cause of neuronal death after global cerebral ischemia. The purpose of this study was to investigate the potential neuroprotective effects of lamotrigine, a novel antiepileptic drug that inhibits the release of glutamate in vitro, with both behavioral and histological measures of global ischemia in gerbils. METHODS: The common carotid arteries of gerbils were occluded for either 5, 10, or 15 minutes. Twenty-one days after reperfusion, gerbils were tested for impairments in a spatial memory task (Morris water maze). After water maze testing the animals were killed, and damage to hippocampal pyramidal cells was assessed. The effect of lamotrigine on the behavioral and histological outcome of either 5 or 15 minutes of global ischemia was evaluated. RESULTS: Bilateral occlusion of the common carotid arteries for 5 minutes resulted in severe degeneration of hippocampal CA1 and CA2 pyramidal cells. Lamotrigine significantly prevented loss of hippocampal CA1 neurons when administered acutely (100 mg/kg PO) immediately after reperfusion or when administered in two equal doses of 30 or 50 mg/kg 2 hours before and immediately after reperfusion. Gerbils subjected to 5 minutes of ischemic insult were not impaired in their ability to solve a spatial memory task 21 days after cerebral ischemia. However, gerbils subjected to 10 and 15 minutes of carotid artery occlusion showed significant impairment in their ability to solve a water maze task. Lamotrigine significantly protected against the cognitive deficits associated with 15 minutes of cerebral ischemia. Histologically, increased durations of cerebral ischemia resulted in a progressive loss of CA1, CA2, and CA3 pyramidal cells. Lamotrigine completely protected gerbils exposed to 15 minutes of cerebral ischemia against CA3 cell loss and greatly reduced damage to the CA1 and CA2 cell tracts of the hippocampus. Lamotrigine also reduced the mortality associated with 15 minutes of ischemia. CONCLUSIONS: Lamotrigine had neuroprotective effects in a gerbil model of global cerebral ischemia. Lamotrigine protected gerbils against behavioral deficits resulting from 15 minutes of carotid occlusion and also prevented histological damage resulting from 5 and 15 minutes of global cerebral ischemia. PMID- 7886727 TI - Effect of intracarotid administration of 6-aminonicotinamide on cerebral blood flow in cats. AB - BACKGROUND AND PURPOSE: We evaluated the effects of an adenosine triphosphate blocker, 6-aminonicotinamide (6-ANA), on the cerebral blood flow (CBF), cerebral metabolism, and electroencephalogram of cats. METHODS: Catheters were inserted into the common carotid artery of 16 adult cats anesthetized with ketamine via the lingual artery. We measured CBF in the infused area by the inhaled hydrogen gas clearance method and analyzed the electroencephalogram frequency. Cerebral metabolism was estimated by oxygen extraction (vol/%) and glucose utilization (millimoles) using data arterial (aorta) and sagittal sinus blood samplings. A solution of 6-ANA (6.0 mg/mL) (n = 8) or saline (n = 8) was infused via catheter at 2.0 mL/min for 3 minutes followed by a 60-minute observation of CBF, cerebral metabolism, vascular resistance, and the electroencephalogram components, alpha-2 ratio [= alpha-2/(alpha-1+alpha-2)]. The effect of 6-ANA on capillaries was evaluated by extravasation of Evans blue dye and electron microscopic findings. RESULTS: Moderate reductions in CBF, cerebral metabolism, and the alpha-2 ratio were observed during the infusion of 6-ANA versus saline infusion (P < .05 by paired t test and ANOVA). Vascular resistance was significantly increased (P < .05). No abnormalities were observed in the capillaries of the infused hemisphere. CONCLUSIONS: Results indicated that 6-ANA produced a downregulation of cerebral blood flow in cats. PMID- 7886728 TI - Stroke due to recurrent ipsilateral carotid artery dissection in a young adult. AB - BACKGROUND: Extracranial carotid artery dissection is a well-recognized cause of ischemic stroke. Recurrent carotid artery dissections are infrequent. Recurrent ipsilateral dissection has only rarely been documented and has not been pathologically verified. CASE DESCRIPTION: A 33-year-old woman presented with a left parieto-occipital ischemic stroke. Angiography demonstrated a pseudoaneurysm of the extracranial left internal carotid artery. There was no angiographic evidence of an underlying vasculopathy. The pseudoaneurysm was resected, and microscopic examination revealed features most consistent with fibromuscular dysplasia with areas of both chronic and recent dissection. CONCLUSIONS: This case suggests that the frequency of fibromuscular dysplasia as a cause for "idiopathic" spontaneous carotid artery dissection may be higher than previously recognized and that recurrent embolization may occur in the setting of chronic dissection due to redissection of the previously involved vessel. PMID- 7886729 TI - Hyperglycemia and hemorrhagic transformation of cerebral infarcts. AB - BACKGROUND: Identification of factors that predispose to bleeding into ischemic brain could lead to safer use of thrombolytic agents in the setting of ischemic stroke. Recently de Courten-Meyers and colleagues reported that occluding the middle cerebral artery of markedly hyperglycemic cats was associated with 5-fold more frequent and 25-fold more extensive hemorrhage into infarcts than in normoglycemic animals. Hemorrhage associated with hyperglycemia in cats was much more pronounced with reperfusion than with permanent middle cerebral artery occlusion. CASE DESCRIPTION: We describe two patients with a unique presentation of diffuse hemorrhagic infarction of the caudate and lentiform nuclei associated with initially marked hyperglycemia and the subsequent development of hemichorea. CONCLUSIONS: We hypothesize that the marked hyperglycemia due to poor control of diabetes contributed to the hemorrhagic change of the caudate and lenticular nuclei. Because the hemorrhage in hyperglycemic cats was more pronounced in the setting of reperfusion, hemorrhagic risk associated with hyperglycemia should be investigated, particularly in ongoing thrombolytic treatment trials for acute ischemic stroke. We encourage other acute stroke investigators to prospectively look at the risk of brain hemorrhage in stroke patients with marked hyperglycemia. PMID- 7886730 TI - Hypertensive encephalopathy after bilateral carotid endarterectomy. AB - BACKGROUND: Hypertension occurs frequently after carotid endarterectomy and may lead to cerebral vascular complications and myocardial infarction. Its pathophysiology has recently been related to surgically induced damage of carotid baroreceptors. CASE DESCRIPTION: A 45-year-old normotensive man with no history of epilepsy was admitted 3 weeks after bilateral carotid endarterectomy for severe repetitive paroxysmal headaches, vomiting, and agitation that were closely associated with attacks of marked hypertension. During one of these attacks, he had a grand mal seizure. Plasma catecholamine levels during hypertensive attacks were highly elevated despite the absence of pheochromocytoma, reflecting abnormalities in baroreceptor sensitivity that lead to unrestrained activation of the central sympathetic nervous system. Heart rate response to Valsalva maneuver showed suppression of the usual tachycardia, indicating baroreceptor reflex insensitivity. CONCLUSIONS: We report the first case of hypertensive encephalopathy associated with baroreflex failure syndrome after bilateral carotid endarterectomy. The role of blood pressure monitoring may be critical in revealing carotid baroreceptor insensitivity in such clinical settings. PMID- 7886731 TI - Sneddon's syndrome with granulomatous leptomeningeal infiltration. AB - BACKGROUND: There is limited neuropathologic information available from cases of Sneddon's syndrome in which strokes are associated with livedo reticularis. Pathogenesis of the syndrome is controversial, although current opinion favors a coagulopathy, often with antiphospholipid antibodies. We describe a case lacking antiphospholipid antibodies but having a granulomatous infiltration of the leptomeninges. CASE DESCRIPTION: The patient presented at age 29 with stroke, livedo reticularis, essential hypertension, and Raynaud's phenomenon. Assessment uncovered no underlying disease, including absent antiphospholipid antibodies. A leptomeningeal biopsy showed granulomatous infiltration. CONCLUSIONS: The findings suggest that an inflammatory process plays a role in at least some cases of Sneddon's syndrome. PMID- 7886732 TI - Superior sagittal sinus thrombosis and thyrotoxicosis. Possible association in two cases. AB - BACKGROUND: Superior sagittal sinus thrombosis is an uncommon cerebrovascular accident that is frequently associated with diseases that may contribute to the development of thrombosis through hypercoagulability, stasis of the local blood stream, and abnormalities of the vessel wall. In approximately 25% of cases underlying diseases remain unrecognized. CASE DESCRIPTIONS: Two patients with superior sagittal sinus thrombosis during a thyrotoxic phase of Graves' disease are described. Both patients presented with hemiplegia, seizures, and a large goiter. CONCLUSIONS: The development of superior sagittal sinus thrombosis is multifactorial. Patients with thyrotoxicosis and a large goiter may be predisposed to the development of superior sagittal sinus thrombosis through hypercoagulability and stasis of the local venous blood flow. PMID- 7886733 TI - The Cochrane Collaboration Stroke Review Group. Meeting the need for systematic reviews in stroke care. AB - BACKGROUND: There is a pressing need to identify which interventions are definitely effective in the prevention of stroke and in the treatment and rehabilitation of stroke patients, which interventions are definitely ineffective, and which interventions require further research. This information is most reliably obtained from reviewing all the available evidence from randomized controlled trials in a systematic way. SUMMARY OF COMMENT: There have been many (at least 8000) randomized controlled trials relevant to stroke. It would be difficult for any one individual to keep track of all these trials, and therefore most clinicians, therapists, and researchers are dependent, to some degree, on reviews of this literature. However, most current reviews are unsystematic and tend to be either incomplete or biased, so that their recommendations can be seriously flawed. Until now there has been no attempt to systematically identify all randomized controlled trials relevant to stroke (including subarachnoid hemorrhage), to review the data they contain, and to keep these reviews up-to-date in the light of new evidence. The Stroke Review Group has now been established within the Cochrane Collaboration to try to perform these tasks. There are presently 40 collaborators from 13 countries working on approximately 25 reviews. CONCLUSIONS: Identifying and reviewing all randomized controlled trials relevant to stroke should bring important benefits to patients and all those involved in purchasing or providing care for patients with stroke. The Cochrane Collaboration Stroke Review Group has started this process and would welcome help from anyone interested in collaborating in this enormous task. PMID- 7886734 TI - Clinical experience with excitatory amino acid antagonist drugs. AB - BACKGROUND: Excitotoxic damage due to excess release of neuronal glutamate is hypothesized to play a pivotal role in the pathogenesis of focal cerebral ischemia. Drugs that antagonize excitatory amino acid function are consistently neuroprotective in preclinical models of stroke, and many are now entering clinical trials. SUMMARY: Antagonists of the N-methyl-D-aspartate (NMDA) receptor are furthest advanced in clinical development for stroke. Both noncompetitive (aptiganel hydrochloride, dextrorphan) and competitive (selfotel, d-CPPene) antagonists have undergone tolerability studies in acute stroke and traumatic brain injury. These agents all cause a similar spectrum of neuropsychological symptoms, and several have important cardiovascular effects. Other modulatory sites on the NMDA receptor complex, notably the polyamine and magnesium ion sites, are also the subject of clinical trials. Glycine site antagonists are in early clinical development. Non-NMDA glutamate receptor antagonists remain in preclinical study. Neuroprotection by agents that block glutamate release in vitro may be due to sodium channel blockade in vivo, but some agents (619C89) exhibit neurological effects similar to NMDA antagonists in stroke. The therapeutic index is unknown for different drugs but may be determined by cardiovascular effects, especially hypotension, which may be detrimental after stroke. CONCLUSIONS: Excitatory amino acid antagonists are in advanced development in the treatment of stroke and traumatic brain injury. A similar pattern of side effects is apparent with the majority of agents. However, cardiovascular effects may ultimately define therapeutic index for each drug. PMID- 7886735 TI - The epidemiology of stroke in Native Americans. AB - BACKGROUND AND PURPOSE: Because of the paucity of published information, this report seeks to better characterize the pattern of stroke occurrence and risk factors among Native Americans in the United States. METHODS: Data from the US Vital Statistics System and two National Health and Nutrition Examination Surveys were analyzed. RESULTS: Stroke was a leading cause of death among US Native Americans in 1990. In persons aged 45 and over, stroke was the cause of 6% of deaths in Native Americans and 7% of deaths in whites. The percentage of stroke deaths due to hemorrhagic stroke was higher in Native Americans than whites. In 1988 through 1990, stroke death rates were similar in Native Americans and whites under age 65 but lower in Native Americans at ages 65 years and over. High prevalence of diabetes, smoking, and obesity may contribute to stroke mortality in Native Americans. CONCLUSIONS: Targeted research, innovative analyses of existing data, and use of ongoing surveys and the Census should be considered in the study of the epidemiology of stroke, other leading causes of death, and risk factors in Native Americans. Continued hypertension detection and treatment efforts are needed for Native Americans as for other groups. Smoking cessation and prevention should receive high priority in Native American populations. PMID- 7886736 TI - Anticoagulant treatment or antiplatelet therapy after a single carotid TIA? PMID- 7886737 TI - Value of acute-stage positron emission tomography in predicting neurological outcome after ischemic stroke: further assessment. PMID- 7886738 TI - Microembolic signals inpatients referred for echocardiography. PMID- 7886739 TI - Microembolic signals in patients referred for echocardiography. PMID- 7886740 TI - [Aging in a changed Europe. 3rd European Gerontology Congress in Amsterdam, 30 August-2 September 1995]. PMID- 7886741 TI - [Nursing home care on the move; a stock-taking overview of 5 substitution projects nursing home care]. AB - An inventory was made of 5 substitute care projects in old people's homes, performed by the nursing home in Geertruidenberg. Data were gathered by semi structured interviews and enquiries. The general goal of substitution of nursing home care for outdoor patients is to provide complementary outreaching nursing home services, by which real nursing home admittance can be postponed or avoided. In fact, in many cases substitution care appears to avoid nursing home admittance. In 1991-1993 there were 144 participants in these projects, from which only 11 at least were admitted to the nursing home. In the near future however, the quality of these outreaching nursing home projects has to be improved, especially on aspects as: continuity and methodology of care and with respect to the multidisciplinary approach. At last the financial support of these projects appears to be complicated and uncertain. A structural solution for this problem is urgent too. PMID- 7886742 TI - [Substitution in psychogeriatrics. A comparative study in nursing homes and substitution projects in Drenthe]. AB - Due to a strong increase of the ageing population in the Netherlands there is a growing need for care for psychogeriatric patients. The shortage of beds in psychogeriatric nursing homes has led to the development of substitute care in residential homes for the elderly and in community centers. If substitution is realized in these substitute care projects in the sense that alternative services are delivered for patients who would otherwise have been admitted to nursing homes, the level of impairment and disruptive behaviour should be of the same level in nursing homes and substitute care projects. Groups of patients of three nursing homes, three day-treatment facilities, eight day-care-projects in residential homes for the elderly and seven centers for day-care in the community were compared. Sociodemographic characteristics, behaviour and care-patterns of all 670 patients who were in care on the first of October of 1992 in these services were investigated. An assessment-scale for elderly patients, based on the Stockton Geriatric Rating Scale, was used to investigate behaviour. Substitute care appears to be possible for a limited and specific group of patients. Substitution for the severely disturbed patients (over 40% of the nursing home patients) does not seem to be possible. Due to the development of substitute care for psychogeriatric patients in residential homes for the elderly and centers for day-care in the community, services seem to develop towards more specific and specialized care. We recommend the foundation of a psychogeriatric case register, which allows the study of the transfer of patients across facilities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886743 TI - [Elderly, science and policy: NESTOR symposium (Netherlands Stimulation Program Elderly Research)]. PMID- 7886744 TI - [The Behavior Observation Scale for Intramural Psychogeriatrics and clinical diagnosis; a comparison with the BOP (Assessment Elderly Patients) and NOSIE-30]. AB - Using a stepwise discriminant analysis we examined the Dutch observational ward behaviour scale GIP in relation to DSM-III-R classification. The GIP was compared to older rating-scales like the BOP and NOSIE-30 in a psychiatric observation clinic for the elderly. Nurses' observations based on the GIP are highly related to clinical diagnosis. Two hundred and ten patients with a dementia syndrome, other organic mental disorders, schizophrenia or mood disorders are correctly classified in 85.7% of the cases, compared to 74.3% and 72.8% with the BOP and NOSIE-30. GIP subscales were also significantly and exclusively correlated with severity of dementia and depression. However, the original GIP norms, based on observation in a chronic psychiatric population, are inadequate for the description of newly admitted elderly psychiatric patients. PMID- 7886745 TI - [Contributions to the quality of care in homes for the aged from a psychogeriatric nursing home]. AB - The knowledge and experiences of the staff of a psychogeriatric nursing home can be used to improve the care for residents with psychogeriatric problems of a home for the aged. Staff members of the nursing home Nieuw Toutenburg in Noordbergum taught psychogeriatrics in eleven homes for the aged. Subsequently a psychologist and a nurse provided additional support during eight months. The use of care schemes and staff meetings concerning the care-planning for the residents were introduced. In the homes for the aged knowledge about psychogeriatrics tested by 89 course participants increased and remained stable over a period of at least three months. The care organization in the homes had changed: systematic reports about the residents with psychogeriatric problems were made and staff meetings for care-planning were regularly held. These changes persisted over at least three months after the staff of the nursing home had withdrawn. PMID- 7886746 TI - Hypertension and stroke in sub-saharan Africa. PMID- 7886747 TI - Malnutrition and the immune response. 1. Malnutrition in the community: recent concepts. AB - Anthropometric indicators have long been used to define the nutritional status of children although anthropometric studies of adult nutritional status have been accorded low priority. As a result, the nutritional status of a community is largely based on estimates of childhood undernutrition alone. The prevalence of adult undernutrition is also variably estimated since objective measures of adult undernutrition are not applied. Body mass index may provide an ideal method for filling this gap since this simple anthropometric index well reflects the physiological, social and economic consequences of adult undernutrition in a community. It also enables assessment of the impact of intervention strategies aimed at developmental or public health outcomes in population groups world-wide. PMID- 7886748 TI - Malnutrition and the immune response. 2. Impact of nutrients on cytokine biology in infection. AB - Interleukins 1 and 6 and tumour necrosis factor orchestrate a co-ordinated series of metabolic changes following invasions by pathogens. The changes are designed to destroy the pathogen. The response is characterized by fever, proteolysis in peripheral tissues, acute phase protein and antioxidant synthesis, and enhancement of the activity of the immune system. Cytokine production is enhanced by free radicals. Damage to the host may occur as a consequence. The deterious actions of these molecules are held in check by sophisticated antioxidant defences and systems which exert feedback control on cytokine biology. Nutrients have a profound effect upon the production and actions of cytokines. Protein energy malnutrition, dietary n-3 polyunsaturated fatty acids and vitamin E suppress cytokine production and actions. An opposite influence is exerted by n-6 polyunsaturated fatty acids, poor antioxidant defence, and supplementation of the diet with protein and branched chain amino acids. The synthesis of acute phase proteins and glutathione is dependent upon the adequacy of dietary sulphur amino acid intake. The consequences of the modulatory effects of previous and concurrent nutrient intake on cytokine biology are depletion of resources and damage to the host, which ranges from mild and temporary to severe, chronic or lethal. PMID- 7886749 TI - Control of endophagic Anopheles mosquitoes and human malaria in Guinea Bissau, West Africa by permethrin-treated bed nets. AB - We compared the anti-mosquito and antimalarial potentialities of placebo-treated versus permethrin-impregnated bed nets in north-western Guinea Bissau. Baseline, pre-intervention entomological and parasitological data were collected during the rainy season of 1990 and bed nets were distributed shortly before the rainy season of 1991. Pairs of 3 ethnically different villages were investigated. The villages in each pair were at least 2 km apart but belonged to the same ethnic group in an ecologically similar area. After one year permethrin-treated bed nets were provided to all people in one village of each pair and placebo-treated bed nets to the other villages. About 98% of mosquitoes caught in bedrooms belonged to Anopheles gambiae and A. melas, which we consider to be the main malaria vectors in the study villages. Mean Plasmodium falciparum sporozoite rate in A. gambiae (9.6%) and A. melas (12.4%) was highest during October-November. The Plasmodium index in children 2-9 years old in the 6 villages, at the end of the rainy season 1990, ranged between 44% and 79%. Of these, 98% were identified as P. falciparum, 1% as P. malariae and 1% as mixed infections of these species. Significant reductions of Anopheles indoor resting densities and malaria parasite rates in humans were recorded in villages which had received permethrin-treated nets, but not in the control villages. The mean number of P. falciparum-infective mosquito bites received indoors in untreated villages during the rainy season was estimated to be about 4 per child and 20 per adult. This inoculation rate was reduced by at least 78% by the use of permethrin-impregnated bed nets. The malaria parasite rates and proportions of people experiencing 'disease with fever' decreased significantly in villages provided with permethrin-treated nets but not in the control villages. Impregnated nets may be an important tool to reduce disease and death due to malaria in Guinea Bissau. PMID- 7886750 TI - Alphamethrin-impregnated bed nets for malaria and mosquito control in China. AB - A community-based intervention trial was carried out to evaluate the effectiveness of alphamethrin-impregnated bed nets for control of Plasmodium vivax malaria and its vector in an area of moderate endemicity in southern Henan province, central China in 1990. Malaria incidence was significantly lower in the intervention group than in the comparison group (2.03 vs. 3.57 per 100 person years at risk). The protective efficacy for malaria incidence was 43%. The prevalence of malaria parasitaemia among children under 10 years old in the intervention group was about one-quarter of that in the comparison group (0.93% vs. 3.25% and 0.71% vs. 1.96% after one and 4 months use of impregnated nets, respectively). Alphamethrin-impregnated bed nets had a mass killing effect on vector mosquitoes. The outdoor person-biting density of Anopheles anthropophagus and A. sinensis decreased by 70.3% and 29.3% respectively. The density of these 2 mosquito species found resting inside treated nets was close to zero. No side effect was found among users of impregnated bed nets. Impregnation with alphamethrin was more effective on polyester than on cotton netting and residual effects lasted at least one year. Use of alphamethrin is less expensive than permethrin and deltamethrin. PMID- 7886751 TI - The effect of DDT spraying and bed nets impregnated with pyrethroid insecticide on the incidence of Japanese encephalitis virus infection. AB - A retrospective investigation was conducted to evaluate the effectiveness of DDT residual indoor spraying and bed nets impregnated with pyrethroid insecticide for Japanese encephalitis control in southern Henan province, China. DDT residual indoor spraying had no effect on the incidence of Japanese encephalitis, but it was greatly reduced after the introduction of pyrethroid-impregnated bed nets. Only a small effect on outdoor biting densities of Culex tritaeniorhyncus was found, although the number of mosquitoes resting inside bed nets decreased markedly after the introduction of bed net impregnation. PMID- 7886752 TI - The protective effect of bed nets impregnated with pyrethroid insecticide and vaccination against Japanese encephalitis. AB - A population-based case-control study to evaluate the protective effect of bed nets impregnated with pyrethroid insecticide and of vaccination against Japanese encephalitis was carried out in Gusi county, Henan province, China from June to September 1991; 50 cases and 100 matched controls were studied. Bed nets impregnated with pyrethroid insecticide greatly decreased the risk of infection among children under 10 years old, and vaccine efficacy was 78% (95% CI 16%-94%). We suggest that impregnated bed nets could be used as a quick response during outbreaks of Japanese encephalitis. PMID- 7886753 TI - Child weighing by the unschooled: a report of a controlled study of growth monitoring over 12 months of Maasai children using direct recording scales. AB - Growth monitoring was developed as a clinic-based programme in the early 1960s, and has spread widely in many countries. The results of weighing children are usually presented in a graphic form, unintelligible to most mothers and difficult for many health workers to interpret. This study suggests that the TALC Direct Recording Scale will allow growth monitoring to be undertaken even by illiterate mothers in the community and reports the results of a trial with a group of illiterate mothers amongst the Maasai of Kenya. PMID- 7886754 TI - Malaria prevalence is inversely related to vector density in The Gambia, West Africa. AB - Baseline epidemiological and entomological studies were conducted in 5 different areas of The Gambia before the introduction of a national malaria control programme, the objective of which was to treat all the bed nets belonging to people living in primary health care villages with insecticide. All malariometric indices used (parasite density, parasite rates, splenomegaly, and packed cell volume) indicated that malaria transmission was more intense in the east of the country than elsewhere. High transmission in the east was associated with a high sporozoite rate but not with the greatest vector abundance; the lowest malaria prevalence rates were found in villages which were close to very productive breeding sites of Anopheles gambiae s.l. Bed net usage was strongly correlated with vector density and the highest malaria rates were found in villages where bed net usage was relatively low. These results suggest that in The Gambia malaria prevalence rates are reduced where nuisance biting by mosquitoes is sufficient to encourage the population to protect themselves with bed nets. PMID- 7886755 TI - Malaria in the oasis of Bilma, Republic of Niger. PMID- 7886756 TI - Measurement of risk in endemic areas of human African trypanosomiasis in Cote d'Ivoire. AB - An index of epidemiological risk was developed for the foci of human African trypanosomiasis (HAT) in the forest zone of Cote d'Ivoire, based on the following characteristics of Glossina palpalis palpalis populations: daily survival rate, apparent density of teneral males and females, and frequency of human-fly contact. The index agreed well with HAT prevalence. It varied according to ethnic groups and with seasonal changes in agricultural activities and fell rapidly to zero following the start of an anti-vector control campaign. Further studies in different biogeographical zones are desirable in order to substantiate the validity of the index. PMID- 7886757 TI - Changing patterns of cutaneous leishmaniasis in Israel and neighbouring territories. AB - The most frequent form of cutaneous leishmaniasis (CL) in Israel and the neighbouring territories is due to Leishmania major, which is endemic mainly in the Jordan Valley and in the Rift Valley. CL due to L. tropica is much less common, and in the past only sporadic cases have been reported. In this study we present data obtained during the years 1988-1992 regarding CL in the area. Our clinic has diagnosed a total of 371 leishmaniasis cases, most of whom acquired the infection in the Jordan Valley, mainly during June and July. About one-third of the patients had single lesions, and one-third more than 5 lesions. We also describe an outbreak of leishmaniasis in Kfar Adumim, a village 15 km east of Jerusalem, where leishmaniasis was previously unknown. Parasites were characterized by the polymerase chain reaction and by immunostaining, and found to be both L. tropica and L. major. The localization of the homes of the affected people on a slope where hyraxes were abundant suggests that these animals might have been involved in the transmission of L. tropica in this area. PMID- 7886758 TI - Asymptomatic visceral leishmaniasis in Israel. PMID- 7886759 TI - Schistosomiasis in Dogon country, Mali: identification and prevalence of the species responsible for infection in the local community. AB - The prevalence of schistosomiasis amongst the Dogon people in 4 villages and one school of the Bankass district of Mali was determined during 2 surveys in 1992; 1398 urine and 1199 stool samples were examined. The most common schistosome was Schistosoma haematobium, with an overall prevalence of 51.3%; S. mansoni had a prevalence of 12%. No S. intercalatum egg was seen in the stools. Biomphalaria pfeifferi and Bulinus truncatus were found in pools at the base of the Dogon cliffs; Bulinus forskalii was found in smaller numbers in brick pits. Two isolates from urine samples of children were identified as S. haematobium in the laboratory using an alpha-glycerophosphate marker, restriction enzyme analysis of ribosomal deoxyribonucleic acid (rDNA) and random amplification of polymorphic DNA. The isolates did not develop in Bulinus forskalii or B. crystallinus of the B. forskalii group. Some evidence for past hybridization of S. haematobium and S. intercalatum is provided by the enzyme and rDNA results as well as the positive Ziehl-Neelsen staining of polymorphic eggs in urine samples. The findings are discussed in relation to the published observations concerning schistosomiasis in travellers returning from this region of Mali. PMID- 7886760 TI - Anti-HCV antibody prevalence among an asymptomatic population living in two villages in Madagascar. PMID- 7886762 TI - Agglutinating anti-leishmanial antibodies in the saliva of kala-azar patients. PMID- 7886761 TI - Use of the leishmanin skin test and western blot analysis for epidemiological studies in visceral leishmaniasis areas: experience in a highly endemic focus in Alpes-Maritimes (France). AB - Fifty unselected subjects living in Alpes-Maritimes, France, a high risk area for visceral leishmaniasis due to Leishmania infantum, were examined simultaneously by the leishmanin skin test and the Western blot technique in 1993; 32% and 38%, respectively, gave a positive reaction. The concordance of the 2 methods was 82%. Thus, in this high risk area, a large proportion of inhabitants had been exposed to the parasite. The use of these 2 tests should permit the detection of potential cases of reactivated leishmaniasis in prospective follow-up investigations. PMID- 7886763 TI - Low positive predictive value of anti-Brugia malayi IgG and IgG4 serology for the diagnosis of Wuchereria bancrofti. AB - Enzyme-linked immunosorbent assays (ELISAs) for anti-Brugia malayi immunoglobulin (Ig) G and IgG4 were evaluated on sera from 1561 subjects in French Polynesia for the serodiagnosis of Wuchereria bancrofti filariasis, compared with the test for Onchocerca gibsoni circulating antigen (Og4C3) as a 'gold standard'. The sensitivity of the ELISA-IgG and ELISA-IgG4 assays was 90.8% and 94.5%, and the specificity was 45.9% and 50.7%. The positive predictive values were 41% and 45% respectively for an antigen prevalence rate of 30%. Thus antibody prevalences exceeded by two-fold the antigen prevalence, which itself exceeded by two-fold the prevalence of microfilaraemia. PMID- 7886764 TI - Immunodiagnosis of human sparganosis mansoni by micro-chemiluminescence enzyme linked immunosorbent assay. AB - We compared a microcolorimetric enzyme-linked immunosorbent assay (colorimetric ELISA) and a microchemiluminescence enzyme-linked immunosorbent assay (chemiluminescence ELISA) for the detection of specific immunoglobulin G (IgG) in the serum of 9 patients with sparganosis mansoni and 9 healthy controls. The chemiluminescence ELISA was able to measure serum levels of specific IgG over a far wider range than the colorimetric assay, and its detection limit was at least 10-fold lower. An additional 5 sera from sparganosis patients and 5 more from healthy controls, together with sera from 28 patients with other parasitic diseases, were also examined by the chemiluminescence ELISA. All 14 patients with sparaganosis mansoni showed high levels of chemiluminescence (21,302 +/- 18,907 counts per second [cps]). All sera from the 14 healthy controls (1580 +/- 569 cps) and sera from 27 of the 28 patients with other parasites (4 with taeniasis saginata [1767 +/- 501 cps], 11 with diphyllobothriasis latum [1479 +/- 501 cps], 13 with cysticercosis cellulosae [2376 +/- 1437 cps]) showed chemiluminescence levels lower than those of any of the sparganosis mansoni patients. The exception was a patient with cysticercosis (5980 cps), who may have had a dual infection with Cysticercus cellulosae and Sparganum mansoni. Thus, the chemiluminescence ELISA demonstrated high sensitivity and specificity for human sparganosis mansoni. PMID- 7886765 TI - Detection of Wuchereria bancrofti larvae in pools of mosquitoes by the polymerase chain reaction. PMID- 7886766 TI - Serum tumour necrosis factor in children suffering from Plasmodium falciparum infection in Kilifi District, Kenya. AB - Tumour necrosis factor-alpha (TNF alpha) levels were measured by bioassay and immunoassay in sera of children infected with Plasmodium falciparum and uninfected children in the same community in Kilifi District, Kenya. Seventy-one children, mean age 2.9 years (range 4 months-6.8 years), were enrolled; 34 children had severe malaria, 23 had mild (non-severe) malaria and 14 had no malaria. TNF alpha levels were significantly elevated in children with severe malaria compared with those with non-severe malaria and the uninfected group (P < 0.001 and P < 0.00001, respectively). The levels correlated directly with parasite densities (r = 0.54, P < 0.002). Among the children with severe malaria, TNF alpha levels correlated directly with the degree of anaemia but inversely with age. High tumour necrosis factor levels were associated with manifestations of severe malaria infection but declined to normal levels after effective antimalarial treatment. PMID- 7886767 TI - Serum procalcitonin concentrations in acute malaria. PMID- 7886768 TI - Dengue haemorrhagic fever in the state of Rio de Janeiro, Brazil: a study of 56 confirmed cases. AB - We studied 56 cases of serologically confirmed dengue haemorrhagic fever living in the metropolitan area of Niteroi and surrounding cities in the state of Rio de Janeiro, Brazil. The most frequent findings were fever and myalgia. Spontaneous haemorrhagic manifestations occurred in 46 patients, and 23 of these had more than one kind of bleeding; petechiae and bleeding gums were the most frequent association. The distribution according to the World Health Organization's criteria of severity was 6 in grade I, 23 in grade II, 24 in grade III and 3 in grade IV. PMID- 7886769 TI - Human Taenia cysticercosis: a bizarre mode of transmission. PMID- 7886770 TI - Can malaria chemoprophylaxis be restricted to first pregnancies? AB - The harmful effects of malaria are most pronounced during first pregnancies and chemoprophylaxis is most effective when given at this time. However, restriction of chemoprophylaxis to first pregnancies might lead to enhanced susceptibility to malaria during second pregnancies. We have investigated this possibility by studying the outcome of second pregnancies in 165 Gambian women who had received either malaria chemoprophylaxis with Maloprim or placebo during their first pregnancy. Many of these primigravidae did not present until the third trimester of pregnancy so that some are likely to have experienced a malaria infection before they started medication. The prevalence of malaria infection of the blood and of the placenta during second pregnancies was similar in women who had received chemoprophylaxis during their first pregnancy and in those who had not, and the mean birth weights of babies born to women in each group were almost identical. Thus, in areas where the epidemiology of malaria is similar to that of The Gambia and where most women present relatively late in pregnancy, it may be possible to restrict malaria chemoprophylaxis to first pregnancies with consequent savings in cost and a reduction in drug pressure on Plasmodium falciparum. PMID- 7886771 TI - In vitro drug interaction between amantadine and classical antimalarial drugs in Plasmodium falciparum infections. AB - The interactions of amantadine with classical antimalarial drugs were evaluated against a chloriquine-resistant and a chloroquine-sensitive strain of Plasmodium falciparum in vitro. Amantadine potentiated the effect of chloroquine and quinine in both strains; it also potentiated the effect of mefloquine, halofantrine and primaquine in the chloroquine-resistant strain but had no effect in the chloroquine-sensitive strain. Amantadine had no effect on the response to pyrimethamine of either strain. Amantadine does not interfere with the activity of these compounds and may possibly enhance it. PMID- 7886772 TI - The effect of curdlan sulphate on in vitro growth of Plasmodium falciparum. PMID- 7886773 TI - Single dose artemisinin-mefloquine treatment for acute uncomplicated falciparum malaria. AB - For the treatment of patients with acute falciparum malaria, the combination of artemisinin as a single dose with a single dose of mefloquine was studied in 4 separate prospective trials, comprising 405 adults and 139 children with uncomplicated falciparum malaria in 2 in-patient and 2 rural out-patient studies in Viet Nam. Adults received oral artemisinin and children artemisinin suppositories. Randomized comparative treatment schedules were: artemisinin alone for 5 d, mefloquine-sulfadoxine-pyrimethamine (MSP), or quinine plus sulfadoxine pyrimethamine (SP). Parasite clearance times (PCT) were rapid for artemisinin treated inpatients (90%: 14.8-20.4 h) but also for patients receiving MSP (PCT 90%: 18.0 h) and quinine (PCT 90%: 22.5 h). The recrudescence rate (RI) during a 28 d follow-up period among the patients given artemisinin plus mefloquine was 15% in the adult in-patients and zero in the adult and children out-patients. RI in the artemisinin 5 d treatment group was 33.3%; among those given artemisinin plus SP it was 47.3% in in-patients and in out-patients 46.1%. In the MSP treated out-patients RI was 1.5% in adults and zero in children. Artemisinin as a single dose (oral in adults and as a suppository in children) in combination with mefloquine was effective in rapidly lowering parasitaemia and in preventing recrudescence in hospital in-patients and in out-patients attending a rural health clinic. MSP alone as a single dose also rapidly reduced parasitaemia (but not as quickly as the artemisinin-mefloquine combination in out-patient children) and prevented recrudescence. PMID- 7886774 TI - The efficacy of WR238605 against the blood stages of a chloroquine resistant strain of Plasmodium vivax. PMID- 7886775 TI - Multiresistant falciparum malaria cured using atovaquone and proguanil. PMID- 7886776 TI - Chloroquine resistance of Plasmodium falciparum: further evidence for a lack of association with mutations of the pfmdr1 gene. PMID- 7886777 TI - Limited efficacy of injectable aminosidine as single-agent therapy for Colombian cutaneous leishmaniasis. AB - Ninety military patients with cutaneous leishmaniasis in Colombia were randomly allocated to 3 treatment regimens of parenteral aminosidine sulphate: (i) 12 mg aminosidine base/kg/d for 7 d, (ii) 12 mg/kg/d for 14 d, and (iii) 18 mg/kg/d for 14 d. With the 89 evaluable patients, the cure rates 12 months after the end of treatment were 10%, 45%, and 50%, respectively. Fifty-eight of the 66 patients who were not cured had lesions that enlarged or were unchanged by 1.5 months after treatment follow up. The other 8 patients had lesions that relapsed between 3 and 12 months after therapy. Even in group (iii) the cure rate was inferior to that (> 90%) with antimony or pentamidine previously reported in this patient population. This study indicates that parenteral aminosidine alone is less likely to be successful in the treatment of cutaneous lesihmaniasis than visceral leishmaniasis, for which a 74% cure rate has been reported. Further trials might consider the combination of aminosidine with other antileishmanial drugs. PMID- 7886778 TI - Comparison of glucose versus fat emulsion in the preparation of amphotericin B for use in kala-azar. PMID- 7886779 TI - Aminosidine (paromomycin) versus sodium stibogluconate for the treatment of American cutaneous leishmaniasis. AB - The efficacy of aminosidine was compared with sodium stibogluconate in an open, randomized study of parasitologically-proven cutaneous leishmaniasis in Belize. Aminosidine, 14 mg/kg/d (max. 1 g daily) for 20 d, healed 10 of 17 lesions and sodium stibogluconate, 20 mg/kg/d for 20 d, healed 15 of 17 lesions. Lesions caused by Leishmania braziliensis were relatively unresponsive to aminosidine. Aminosidine was well tolerated and toxicity was not observed. Sodium stibogluconate was not well tolerated and treatment was associated with bone marrow suppression and elevation of serum aminotransferases. PMID- 7886780 TI - Sensitivity of Trichomonas vaginalis, Tritrichomonas foetus and Giardia intestinalis to bacitracin and its zinc salt in vitro. AB - The activity of bacitracin in vitro against Giardia intestinalis, Trichomonas vaginalis and Tritrichomonas foetus was enhanced 5-10 times by equimolar concentrations of zinc. Bacitracin and bacitracin zinc activity was tolerant to either aerobic or anaerobic culture conditions and equally effective against T. vaginalis isolates sensitive or insensitive to metronidazole. This enhancement was not due to zinc toxicity and was zinc dose dependent. PMID- 7886781 TI - Double-blind controlled trial of a single dose of the combination ivermectin 400 micrograms/kg plus diethylcarbamazine 6 mg/kg for the treatment of bancroftian filariasis: results at six months. AB - In 1993, a three-arm double-blind controlled trial was implemented in French Polynesia to compare the tolerance and efficacy of a single dose of the combination ivermectin (IVR) 400 micrograms/kg plus diethylcarbamazine (DEC) 6 mg/kg vs. IVR 400 micrograms/kg alone vs. DEC 6 mg/kg alone, for treatment of Wuchereria bancrofti carriers. Of the 57 treated male patients in whom microfilaria (mf) densities ranged from 22 to 4709 mg/mL, 3 groups of 19 were randomly selected and allocated to one of the 3 treatments. Side effects were experienced by 34 patients (60%), but none suffered a severe reaction. Grade of reaction did not differ between treatment group, but was significantly correlated with the pretreatment mf density. Six months after treatment, 26%, 32% and 53% of patients were amicrofilaraemic in the DEC, IVR and IVR+DEC groups, respectively. Mf levels were 6.3%, and 3.1% and 1.0% of the pretreatment level, respectively, significantly lower in the IVR+DEC group than in both the IVR and DEC comparison groups. The combination IVR+DEC showed promise in term of sustained mf decrease, and could be an effective alternative for lymphatic filariasis control programmes. PMID- 7886782 TI - A community study of T lymphocyte subsets and malaria parasitaemia. AB - In a community survey of 312 children aged 3-6 years in urban Guinea-Bissau, we examined Plasmodium falciparum parasitaemia and T cell subsets. 183 children (59%) had parasites in their blood, 13 had fever > or = 37.5 degrees C, and 9 (3%) had fever and a parasite density > 5000/microL (clinical malaria). Compared with children with no parasitaemia or asymptomatic parasitaemia, children with acute malaria had lymphopenia and significantly lower total CD4 and CD8 cell counts, but there was no significant difference in white blood cell count percentages of CD4 and CD8 cells, or the CD4/CD8 ratio. Children with parasitaemia but without fever had a significantly lower percentage of CD4 cells than children without parasites (P = 0.031), but did not differ in any other haematological index. Controlling for other factors, the CD4 cell percentage was inversely correlated with the density of malaria parasites (P = 0.024), whereas there was no association with CD8 cell percentage or the CD4/CD8 ratio. Asymptomatic parasitaemia may be an important confounder in general community studies of T cell subsets in the tropics. PMID- 7886783 TI - Routine vitamin A supplementation, fever, and nutritional status in Malawian children during a drought. PMID- 7886784 TI - Fatal yellow fever contracted at the Hospital for Tropical Diseases, London, UK, in 1930. PMID- 7886785 TI - How much does a malaria parasite weigh? PMID- 7886786 TI - The TALC direct recording scales in Nepal. PMID- 7886787 TI - Immunomodulation by soluble HLA class I. PMID- 7886789 TI - Adenovirus-mediated gene transfer in the transplant setting. Part III. Variables affecting gene transfer in liver grafts. AB - We have established a system of efficient gene transfer to liver grafts using adenovirus vectors. The purpose of this study was to examine variables affecting gene transfer to rat liver grafts during cold preservation. Our results demonstrate that gene transfer efficiency was directly correlated with the ratio of vector to hepatic cells (multiplicity of infection [MOI] and the length of exposure to the vector. At MOIs of 10:1 and 50:1, the hepatic cell transduction rate was 25-30% and 100%, respectively. However, higher MOI was associated with significant mortality. Prolonging the cold preservation/exposure time resulted in an increased transduction rate (50% at MOI of 10:1). Similar gene transfer efficiencies were observed when the vector was diluted in lactated Ringer's or University of Wisconsin solution. Recombinant protein production was evident within 12 hr after reperfusion, and increased to a peak level within 48 hr. These results suggest a predictable pattern of gene transfer and expression after ex vivo transduction of liver grafts with adenovirus vectors. These data are essential in directing desirable levels of recombinant protein within the transplanted organ. PMID- 7886788 TI - Prolongation of allogeneic heart graft survival in rats by administration of a peptide (a.a. 75-84) from the alpha 1 helix of the first domain of HLA-B7 01. AB - Allospecific T lymphocytes mediate graft rejection through specific, direct or indirect, recognition of processed determinants of foreign MHC class I molecules. Small synthetic peptides derived from highly conserved sequences of the alpha 1 helix of the first domain of certain MHC class I molecules have been shown to inhibit CTL responses in vitro and to prolong graft survival in rats when combined with subtherapeutic doses of cyclosporine. Here, we report that the survival of LEW.1W heart allografts was significantly prolonged when transplanted into congenic LEW.1A recipients treated only with a peptide corresponding to residues 75-84 of the human HLA-B7-01 molecule (B7.75-84) before transplantation. The experimental value for mean survival time (+/- SD) in untreated recipients was 13 +/- 6 days and in peptide-treated recipients was 42 +/- 27 days (P < 0.002). A total of 64% of treated recipients had a functioning graft at 30 days, while grafts were rejected in all rats belonging to the control group within this time. Within graft-infiltrating leukocytes (GIL) in B7.75-84-treated animals, the proportion of T cells was significantly lower and that of CD5-/TCR alpha beta /CD16-/CD8+ and MHC class II+ cells concomitantly increased, as compared with nontreated animals. GIL from B7.75-84-treated animals also exhibited a dramatic decrease (approximately 70%) of allospecific and spontaneous (NK) cytotoxic activity, whereas their proliferation and IL-2 production were similar in both experimental groups. The IFN-gamma, IL-2, and IL-10 mRNA levels from GIL from peptide-treated recipients were similar to levels of controls, reflecting a state of activation of GIL. Perforin and granzyme A mRNA, the level of which may be modulated parallel to impaired cytotoxic functions, were at similar levels in both experimental groups. These data demonstrate that B7.75-84 significantly prolongs graft survival in LEW.1A rats when given as a single agent and suggests that a specifically decreased cytotoxic response (allospecific and spontaneous) plays a major role. PMID- 7886790 TI - Primary nonfunction of fatty livers produced by alcohol is associated with a new, antioxidant-insensitive free radical species. AB - The formation of free radicals after orthotopic liver transplantation in the rat correlates with graft failure. Fatty livers from alcoholics transplant poorly, so these studies were designed to examine the effect of alcohol on free radical formation in a rearterialized rat liver transplantation model. Treatment of rats for 3-5 weeks with either a high-fat or an ethanol-containing liquid diet caused characteristic pericentral lipid accumulation. After storage in University of Wisconsin cold storage solution (UW) and transplantation, a reperfusion injury characterized by increased postoperative AST levels (greater than 1500 U/l in about 3 hours) was observed in rats fed high-fat or alcohol-containing diets, whereas parenchymal cell injury was seen much less in low-fat controls. Survival was around 63% in the low-fat group but decreased to 12 and 18% in the high-fat and alcohol groups, respectively. Furthermore, intracellular lipid content correlated inversely with survival. In untransplanted livers, the spin trap alpha phenyl N-tert-butylnitrone (PBN) was infused, and blood samples were collected and extracted with chloroform:methanol. Signals indicative of carbon-centered PBN radical adducts were barely detectable in all untransplanted groups studied by electron paramagnetic resonance. In contrast, a robust 6-line complex spectrum was obtained from all groups studied immediately after 48 hours of cold storage in UW solution and transplantation. A mixture of 3 radical species was identified. Two had coupling constants similar to lipid-derived free radicals, whereas the third is a new species with unique coupling constants and is most likely oxygen derived. In low-fat controls, the signal was reduced significantly by superoxide dismutase (SOD)/catalase; however, SOD/catalase had no effect on free radicals in lipid-loaded livers. Thus, both dietary high fat and alcohol exposure produce a unique SOD/catalase-insensitive free radical species that may be involved in the mechanism of failure of fatty livers after orthotopic liver transplantation. PMID- 7886791 TI - Hepatic release of endothelin-1 after warm ischemia. Reperfusion injury and its hemodynamic effect. AB - This study investigated the release of endothelin (ET)-1 from the liver after warm ischemia/reperfusion (I/R) injury. Wistar rats were subjected to 120 min of warm hepatic ischemia by clamping the hepatic hilum under porto-jugular shunting. Reperfusion was performed by unclamping. The rats were divided into 2 groups receiving intravenous treatment with an anti-ET-1 mAb before ischemia (AET group) and with mouse immunoglobulin G (sham group). Hepatic blood flow was assessed by laser-Doppler flowmetry and reflectance spectrophotometry and was compared between the 2 groups along with the bile flow rate. The ET-1 concentrations of hepatic venous and portal blood were determined in the sham group, and the portal blood endotoxin levels were assayed in both groups. Both groups developed transient hypotension after reperfusion, but hepatic blood flow subsequently showed a significant improvement in the AET group. Hepatic congestion was detected in the sham group by both reflectance spectrophotometry and histological examination. After reperfusion, bile flow was significantly greater in the AET group. The portal endotoxin concentration showed no increase in both groups, and the hepatic venous blood ET-1 level in the sham group was significantly higher until 3 hr after reperfusion compared to the portal blood level. The 30-day survival rate was 50% in the AET group, whereas all the sham rats died within 12 hr. ET-1 was released from the liver after I/R injury and apparently participated in systemic and local hemodynamic changes that affected survival. PMID- 7886792 TI - Nitric oxide donors improve gut function after prolonged hypothermic ischemia. AB - The objective of this study was to determine whether the nitric oxide (NO) donors, spermine NO and 3-morpholinosydonimine-N-ethyl-carbamide (SIN1), alter the mucosal and microvascular responses of the feline small intestine to 6 hr of hypothermic ischemia and 2 hr of normothermic reperfusion. Intestinal mucosal permeability was monitored using the blood-to-lumen clearance of 51Cr-EDTA. Lymph flow and lymphatic protein clearance estimates were used to assess intestinal microvascular fluid filtration and vascular protein leakage, respectively. Spermine NO (0.1 mmol/L) or SIN1 (0.5 mmol/L) was added to the luminal perfusate during the entire reperfusion period. Both NO donors were effective in attenuating the increased mucosal permeability to 51Cr-EDTA and the depressed net water absorption, relative to untreated intestinal preparations exposed to the same protocol. Intestinal lymph flow, lymphatic protein clearance, and capillary hydrostatic pressure were increased by a greater extent in preparations treated with spermine NO. These findings suggest that NO donors may improve mucosal function in intestinal allografts subjected to prolonged hypothermic ischemia. This protective effect on mucosal epithelium appears to be unrelated to an action of the NO donors on the microvasculature. PMID- 7886793 TI - Human pancreas preservation prior to islet isolation. Cold ischemic tolerance. AB - We have retrospectively evaluated islet isolation records collected from 230 consecutive adult pancreases with 146 pancreases fulfilling all criteria for our evaluation. Fifty-six pancreases procured by our local organ procurement team (33 before in situ vascular flush and 23 after in situ vascular flush with University of Wisconsin [UW] solution) were compared with 90 pancreases received from distant centers that were shipped in UW solution after in situ vascular flushing. Cold storage of 3-26 hr preceded islet isolation using collagenase digestion and Ficoll purification. Recoveries of islets were assessed by duplicate counts of dithizone-stained aliquots before and after purification. Isolations were considered successful if > 100,000 viable islets (islet equivalents to 150 microns) were recovered after purification. Islet function was assessed by in vitro glucose-stimulated perifusion and islets were considered viable if the stimulation index (glucose stimulated over basal insulin secretion) was > 2. Eighty-three percent of the isolations from locally procured, UW-flushed pancreases were successful, as compared with 86% for pancreases that were stored for 3 to 8 hr, 73% for 8 to 16 hr of storage, and 38% for isolations following > 16 hr of cold storage. Increasing the duration of cold storage prior to islet isolation was associated with an increased proportion of failed isolations and decreased measures of islet viability. The actual numbers of islets per gram of pancreas before and after purification were significantly reduced if the hypothermic cold storage was > 16 hr. In vitro viability of isolated islets during glucose-stimulated perifusion showed a higher percentage of viable islets from pancreases with shorter durations of cold storage. For pancreases with > 16 hr of cold storage prior to islet isolation, islet viability was significantly reduced. We conclude that, with the current methods available to recover and store cadaver donor pancreases and the methods currently used to isolate human islets, yields of purified islets decline significantly from human pancreases that have been subjected to cold storage of > 16-18 hr. PMID- 7886794 TI - Improved small intestinal preservation after lazaroid U74389G treatment and cold storage in University of Wisconsin solution. AB - The small intestine (SI) is highly sensitive to oxygen free radical-induced injury. The most common preservation solution, University of Wisconsin (UW) solution, does not adequately prevent free radical-induced injury. Lazaroids, and U74389G in particular, are a new class of compound that are potent inhibitors of superoxide-mediated lipid peroxidation. We studied the added influence of U74389G to 18-hr cold preservation of rat SI in UW solution. Three groups of rats were studied. In group 1, SI was excised and reperfused immediately. In group 2, SI was stored in UW solution at 4 degrees C for 18 hr. In group 3, U74389G was given to the SI graft before storage and again before reperfusion. Blood reperfusion of the grafts was achieved via connection to the superior mesenteric artery and portal vein of support rats. Functional recovery was assessed using a maltose tolerance test. Weight changes were calculated and histologic studies done. After 30 and 60 min of reperfusion, maltose uptake in group 3 was significantly better than that of the group 2, and returned to control levels. Significantly more tissue swelling was noted in group 3 over control, but the magnitude was less than that of group 2. Less transmural necrosis and villous blunting were noted in group 3 versus group 2; the appearance of the mucosa in group 3 approached that of group 1. We conclude that the use of U74389G treatment in addition to cold storage in UW solution improves recovery of graft function and minimizes morphologic damage to the small intestinal mucosa. PMID- 7886795 TI - Heart preservation using a cavitary two-layer (University of Wisconsin solution/perfluorochemical) cold storage method. AB - To reduce cold ischemic injury of the heart by supplying sufficient oxygen to the heart during preservation, we have developed a new cavitary, two-layer (University of Wisconsin solution/perfluorochemical) cold storage method. The oxygenation of the heart during preservation by this method allows ATP production within the graft and makes it possible to extend preservation time up to 48 hr in the heterotopic rat heart transplant model. PMID- 7886797 TI - Effect of size (mis)matching in clinical double-lung transplantation. AB - Current United Network for Organ Sharing policy requires listing lung transplant recipients with an acceptable donor weight range, but lung size is a function of height, age, sex, and race. Frequently, lung transplant recipients are underweight, which results in a large discrepancy between donor and recipient weights. We reviewed our experience with size discrepancy between donors (D) and recipients (R) of 49 double-lung transplant (DLTX) procedures since July 1990. Pneumoreduction procedures were performed in 11 recipients of lungs judged to be too large at the time of DLTX (right middle lobectomy, 2; lingulectomy, 2; both, 6; right middle lobectomy and bilateral apical resections, 1). Predicted forced vital capacity (FVC) and total lung capacity (TLC) of donors and recipients were calculated. Donors were larger than recipients in general (D:R height = 1.02; D:R weight = 1.46), and, as a result, recipient-predicted lung volumes were smaller than donor-predicted lung volumes (D:R FVC = 1.1; D:R TLC = 1.1). Recipients undergoing pneumoreduction procedures had a significantly greater size discrepancy between donors and recipients; thus, both the ratio of D:R and the difference between D and R predicted FVC and TLC were significantly greater among recipients who underwent pneumoreduction, compared with nonreduced recipients. For recipients in the pneumoreduction group, predicted FVC and TLC were recalculated, with a proportionate amount subtracted based on the number of pulmonary segments removed. When the "corrected" FVC and TLC of the donors were compared with recipient-predicted FVC and TLC, there was no longer any significant difference between reduced and non-reduced groups, which implies that visual estimate of size mismatch at surgery is an accurate measure of size discrepancy. Post-DLTX spirometry showed identical improvement in FVC in patients who had pneumoreduction and those who did not, and survival at 6 months was identical in both groups. We conclude that pneumoreduction had no adverse effect on survival or post-DLTX spirometry, allowing safe use of larger donors in small recipients. Also, because lung size is more a function of height than weight, this study challenges the United Network for Organ Sharing practice of listing recipients with an acceptable donor weight range. PMID- 7886796 TI - Pigmentation and microanatomy of skin regenerated from composite grafts of cultured cells and biopolymers applied to full-thickness burn wounds. AB - Rapid coverage and epithelial closure of extensive burns remains a major requirement for patient recovery. Although many skin substitutes have been described, permanent regeneration of both epithelial and connective tissues after a single surgical application of a skin substitute has not become routine. To replace both dermal and epidermal skin, cultured skin substitutes (CSS) were prepared from autologous keratinocytes and fibroblasts seeded onto collagen glycosaminoglycan (C-GAG) substrates. CSS were applied to excised, full-thickness burns on 5 patients. Histologic analysis showed a fully stratified, hyperkeratotic epidermis within 12 days of grafting with little to no evidence of an inflammatory reaction. Epidermal and connective tissues are interdigitated in analogy to rete pegs and dermal papillae, and the neovascular plexus approximates the dermal-epidermal junction. Transmission electron microscopy identified a continuous basement membrane with hemidesmosomes and anchoring fibrils that connected the epidermis with the underlying connective tissue. Within 14-28 days, the C-GAG had been degraded and replaced by newly synthesized collagen in regenerated connective tissue. Spontaneous repigmentation of healing CSS from passenger melanocytes in keratinocytes culture was observed within 2 months after grafting. Electron microscopy revealed the presence of numerous melanosomes within the keratinocytes, illustrating pigment transfer between melanocytes and keratinocytes after wound closure. These results demonstrate that the CSS develop into functional permanent skin tissue capable of spontaneous repigmentation after grafting onto burn wounds. PMID- 7886798 TI - Beneficial effect of low-dose systemic retinoid in combination with topical tretinoin for the treatment and prophylaxis of premalignant and malignant skin lesions in renal transplant recipients. AB - Renal transplant recipients experience a greatly increased frequency of neoplastic skin lesions, including aggressive squamous cell carcinomas. Recent reports suggest that high doses of systemic retinoids may exert a chemotherapeutic and chemoprophylactic effect. Similarly, topical retinoid, especially tretinoin, has also been shown to be anti-tumoragenic in various settings. Because of the serious toxicity of high-dose systemic retinoid, a protocol was developed that combined topical tretinoin with low-dose etretinate (10 mg daily) for the treatment of frequently occurring dysplastic skin lesions in renal transplant recipients. Seven patients elected to receive combined tretinoin and etretinate therapy, and 4 were treated with tretinoin alone. Clinical evaluations were performed monthly. By 3 months of therapy, 9 of 11 patients exhibited at least a 25% decrease in the number of neoplastic growths. After 6 months, 6 of 8 evaluable patients, including 2 of 3 individuals receiving tretinoin alone, exhibited at least a 50% decrease. Three of 4 patients on the combined regimen and 2 of 3 receiving tretinoin alone for at least 9 months, exhibited a significant decrease in the rate of development of new squamous cell cancers. At the start of treatment, epidermal specimens were almost completely devoid of Langerhans cells (CD1+ cells). Their density increased greatly and in proportion to the duration of therapy. Long term topical tretinoin with or without low-dose oral etretinate seems to be an effective regimen to suppress the development of new tumors and to reduce the numbers of existing lesions in renal transplant recipients. PMID- 7886799 TI - Beneficial effect of one HLA haplo- or semi-identical transfusion versus three untyped blood units on alloimmunization and acute rejection episodes in first renal allograft recipients. AB - Acute allograft rejection is the major risk factor of renal function decline and graft loss. Beside histocompatibility matches and pharmacological immunosuppression, blood transfusion is empirically used to detect responder subjects and to induce immune tolerance. Alloimmunization associated with blood transfusions readily detected by anti-HLA antibodies could induce acute vascular rejection episodes during the early period after grafting. Our open prospective study was aimed at analyzing the 1 year follow-up of 105 successive first cadaver renal transplant recipients according to the transfusion protocol as assessed by anti-HLA antibody production, acute rejection episodes, and graft survival. Our conventional transfusion protocol involved 3 nonphenotyped blood transfusions set up at least 20 days before grafting in a control cohort (group A) and was compared with a single pretransplant HLA haplo- or semi-identical blood transfusion in a successive group of patients (group B). Our results suggest that both protocols were associated with similar 1-year graft survivals (> 96% in both groups) and number of patients experiencing rejection episodes (20.7% in group A; 9.6% in group B; P NS). HLA haplo- or semi-identical transfusion was significantly beneficial in naive patients without previous alloantigen contact by pregnancy or blood transfusions during dialysis. Naive patients in group B did not develop post-transfusion anti-HLA antibodies compared to naive patients in group A (16.6%; P < 0.001), and they experienced significantly less acute rejection episodes (2.7%) compared to group A naive patients (20.8%; P = 0.02). PMID- 7886800 TI - Predominant infiltration of rejecting human renal allografts with T cells expressing CD8 and CD45RO. AB - Subsets of T cells have been identified by the expression of different isoforms of CD45. Some T cells expressing CD45RA (gp220) have been characterized as "naive" in their response to antigens including alloantigens, whereas T cells expressing CD45RO (gp180) have been characterized as "memory" T cells. To examine the potential association between kidney allograft rejection and infiltration with these subsets, immunohistologic labeling of serial frozen sections from 17 nonrejecting and 18 rejecting kidney transplant biopsies was performed. Biopsies were selected on the basis of unambiguous clinical pathological diagnosis, no antirejection therapy within 1 month before biopsy, and enough tissue available for immunohistologic labeling. Sections were labeled for CD3, CD4, CD8, CD45RA, and CD45RO, and slides were evaluated in a masked manner. The numbers of cells were counted in 10 (400x) high power fields (HPF) in each section. The medians of average cell counts were significantly higher in the rejecting compared with nonrejecting group for CD3+, CD4+, CD8+, CD45RA+, and CD45RO+ T cells in both diffuse and aggregate patterns of infiltration. However, the numbers of infiltrating cells per HPF in rejecting grafts were most striking for CD8+ and CD45RO+ cells: 16/18 rejecting vs. 1/17 nonrejecting cases had more than 5 CD8+ cells/HPF. Likewise, 17/18 rejecting vs. 1/17 nonrejecting cases had more than 5 CD45RO+ cells/HPF. In both cases, the difference was most striking for cells infiltrating in a diffuse versus aggregate pattern. Significantly higher CD45RO+ to CD45RA+ ratios were observed in rejecting versus nonrejecting groups, both in the diffuse and aggregate patterns. Within the rejecting cases, the CD45RO+ to RA+ ratio was significantly higher in diffuse versus aggregate patterns of infiltration (P < 0.0002). These results indicate that a significant increase in CD8+, CD45RO+, and the ratio of CD45RO+ to CD45RA+ T cells in a diffuse pattern of infiltration is most characteristic of clinical renal allograft rejection. PMID- 7886801 TI - Methylprednisolone pharmacokinetics, cortisol response, and adverse effects in black and white renal transplant recipients. AB - It is generally assumed that chronic glucocorticoid therapy is similar pharmacologically when administered to either black or white renal transplant recipients, resulting in adrenal suppression, low circulating plasma cortisol concentrations, and a similar degree of drug exposure and toxicity. To examine this theory and to investigate the relationship of glucocorticoid metabolism to steroid-induced adverse effects among specific ethnic groups of renal transplant recipients, 9 black and 9 white male patients chronically receiving methylprednisolone were enrolled. All patients had stable renal function and were matched for age, weight, and time since transplant. Standard pharmacokinetic parameters for methylprednisolone were determined and cortisol responses were characterized by total cortisol area under the concentration curve (AUC), return cortisol AUC, and cortisol suppression half-life. All patients received their daily oral dose of methylprednisolone (mean daily dose = 11 mg for blacks and 11 mg for whites) as an intravenous infusion with serial plasma samples obtained over 24 h. The patients were assessed for the presence of specific cushingoid manifestations (buffalo hump, moon facies) and steroid-associated diabetes. Methylprednisolone and cortisol were analyzed via HPLC. In the black patients, the mean clearance of methylprednisolone (206 +/- 70 ml/hr/kg) was significantly slower with a smaller volume of distribution (0.95 +/- 0.32 L/kg) when compared with the white group (327 +/- 129 ml/hr/kg, P = 0.03; volume of distribution = 1.33 +/- 0.27 L/kg, P = 0.015). Despite chronic methylprednisolone therapy, a definite 24-hr cortisol response pattern was noted in 15 of the 18 patients with a mean total cortisol AUC of 732 +/- 443 ng.hr/ml in blacks and 539 +/- 361 ng.hr/ml in whites (P = 0.17, black vs. white). The mean cortisol suppression half-life was 4.31 +/- 1.54 hr in black recipients and 4.11 +/- 1.49 hr in whites (P = 0.48). The mean return cortisol AUC for the black patients was 327 +/- 279 ng.hr/ml and 370 +/- 207 ng.hr/ml for white patients (P = 0.28). The serum cortisol nadir for black patients was 12.3 +/- 7.2 ng/ml, which was significantly higher than the cortisol nadir in white patients (6.4 +/- 4.4 ng/ml; P = 0.03). A majority (94%) of patients (9 black, 8 white) had moon facies and 27% of patients (3 black, 1 white) had a buffalo hump. While 5 of 9 black patients had steroid associated diabetes, no white patients manifested this adverse effect. The black patients with diabetes had higher cortisol AUCs with lower methylprednisolone clearances than the white group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7886802 TI - The flow cytometric crossmatch in liver transplantation. AB - The role of the cytotoxic crossmatch in liver transplantation is generally considered controversial. The development of the flow cytometric crossmatch has allowed the detection of lower levels of donor-directed IgG than is possible with the conventional crossmatch. This assay has been shown to be useful in renal transplantation. However, with the controversial role of the standard cytotoxic crossmatch, the flow cytometric crossmatch has not been used in liver transplantation. Twenty-seven human orthotopic liver allograft recipients were tested for donor-directed IgG using the flow cytometric crossmatch. Thirteen recipients were identified with either T or B lymphocyte-directed IgG. This group had a significantly increased incidence of clinical rejection (75%) as compared with the negative group (29%, P = 0.02, Fisher's exact test). The differences were greatest with B lymphocyte-directed IgG and the rejections were generally steroid sensitive. In this series, the flow cytometric crossmatch proved to be a better prognostic indicator of rejection than the conventional cytotoxic crossmatch. In addition, the association of a positive flow cytometric crossmatch with rejection indicates that the liver follows the same pattern seen in renal and cardiac grafts. PMID- 7886803 TI - Receiver operating characteristic analysis of serum chemical parameters as tests of liver transplant rejection and correlation with histology. AB - Receiver operating characteristic (ROC) analysis was used to determine the strength of the serum chemical parameters alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase (GGT), total bilirubin, conjugated bilirubin, and the ratio of delta bilirubin to conjugated bilirubin as tests of acute cellular rejection in liver transplant patients. The study consisted of 70 liver biopsies performed between February 1989 and January 1992 on 37 transplant patients who were classified as showing either no rejection (35 biopsies) or moderate to severe rejection (35 biopsies); mild cellular rejection biopsies were not included in this study to highlight any differences between rejectors and nonrejectors. Corresponding serum values for liver enzymes, alkaline phosphatase, GGT, and bilirubin fractions were obtained on the morning of the biopsy. ROC analysis demonstrated that there is no single chemical parameter or combination thereof that can statistically or clinically distinguish patients with acute rejection from those with other etiologies of allograft dysfunction. We also assessed by regression analysis the correlation between histologic features in the biopsies and corresponding serum parameters. The degree of histologic cholestasis was compared with the same-day serum value for total bilirubin, alkaline phosphatase, and GGT. The degree of centrilobular necrosis and the number of apoptotic cells were compared with values for aspartate aminotransferase and alanine amino-transferase. There was no correlation between the serum values and histologic abnormalities. We conclude that serum chemistry values are not good tests for rejection or histologic abnormalities in the liver transplant population; liver biopsy should therefore be performed on a scheduled basis. PMID- 7886804 TI - Rejection of kidney allografts by MHC class I-deficient mice. AB - To evaluate the requirement for CD8+ T cells in kidney transplant rejection, we studied class I-deficient (class I-) mice that had received vascularized renal allografts. Because of the absence of MHC class I expression, these mice are grossly deficient in CD4-CD8+ alpha beta TCR+ cells. Despite the deficiency of CD8+ T cells in naive class I- mice, kidney allografts transplanted into class I- recipients developed significant reductions in renal blood flow and glomerular filtration rate to levels comparable to allograft controls. This functional deterioration was associated with histologic changes consistent with cellular rejection. There were no significant differences in the pattern, severity, or phenotypic character of the cellular infiltrate in allografts transplanted into class I- recipients compared to controls. In fact, substantial numbers of CD8+ T cells were present in these allografts, and the intensity and pattern of anti-CD8 staining was not different from controls. Virtually all of the CD8+ cells in the kidney grafts were class I- and CD4- and co-expressed CD8 alpha and beta chains; the majority were alpha beta TCR+. The CD8+ infiltrating cells were cytotoxic to donor targets but also exhibited activity against class I+ cells bearing self MHC. Despite the marked CD8+ T cell infiltration of grafts, CD8+ T cells could not be detected by flow cytometry in freshly isolated splenocytes from the class I- recipients of allografts. High levels of circulating anti-class I antibodies were present in the serum of class I- recipients of kidney allografts, and these antibodies had unusual specificity in that they appeared to recognize framework epitopes of MHC class I. Thus, class I- mice readily reject kidney allografts. Although the number of CD8+ alloreactive precursors is substantially reduced in class mice, and their specificities are atypical, the pattern and character of the intra-graft CD8+ cellular response is not significantly altered. Thus, factors unrelated to precursor frequency determine the dimension of the intra graft CD8+ response. Such factors might include cellular and/or biochemical properties of microenvironment within the graft. PMID- 7886805 TI - Perforin and granzyme B. Cytolytic proteins up-regulated during rejection of rat small intestine allografts. AB - Perforin and granzyme B are 2 cytolytic proteins specific to activated killer cells, particularly CTL. We have studied the mRNA expression of these 2 proteins by a reverse transcriptase polymerase chain reaction method in a unidirectional model of rat small intestine transplant rejection. The allograft group consisted of Lewis x Brown Norway F1 donors into Lewis recipients. The isograft controls were Lewis donors into Lewis recipients. Grafts were placed heterotopically and no immunosuppression was given. Five animals in each group were killed at postoperative days (POD) 3, 5, 7, 8, 9, 10, 12, and 14. mRNA was extracted and a semiquantitative reverse transcriptase polymerase chain reaction was performed. For the semiquantitative analysis, we compared scintillation counts from excised bands. Results were expressed as a percent activity compared with beta-actin. From the same tissue samples, a histologic evaluation was made and rejection was graded according to severity. The isograft controls showed no evidence of histologic rejection and a very low expression of mRNA for perforin and granzyme B from POD 3-14. In contrast, the allograft group began to show histologic evidence of mild rejection on POD 5. By day 7, rejection was moderately severe and associated with a significant up-regulation of perforin and granzyme B in the allografts compared with the controls (P < 0.01), which persisted through POD 14. Peak expression for perforin and granzyme B was on POD 10 and 8, respectively. We conclude that the up-regulation of perforin and granzyme B in rat small intestine transplant allografts is a useful marker of clinically important rejection. PMID- 7886806 TI - Tolerance to class I-disparate renal allografts in miniature swine. Maintenance of tolerance despite induction of specific antidonor CTL responses. AB - Miniature swine that become tolerant to renal allografts across an MHC class I barrier following a short course of cyclosporine are unresponsive to donor class I antigens in cell-mediated lymphocytotoxicity. However, skin grafts bearing donor class I plus third-party class II antigens are promptly rejected, and the animals then develop marked cell-mediated lymphocytoxic reactivity to donor class I antigens in vitro, but do not reject the kidney transplants. We show here that CTL generation is directed toward the same donor class I antigens as are expressed by the kidney donor, and is not the result of recognition in vitro of the tolerated class I antigen plus peptides of minor antigens shared between the skin graft donor and the stimulator/target cells. We also show that detection by CTLs of peptides expressed by skin but not by kidney is also not a sufficient explantation of the results, since the survival of skin grafts from the kidney donor is also prolonged, even after precursor CTL can be detected in vitro. The data are most consistent with suppression in vivo in tolerant animals of the helper pathways necessary for activation of precursor CTLs. Differences in patterns of cytokine expression by graft infiltrating cells may provide a mechanism for local suppression of help in this model. Finally, we have examined antibody production after sensitizing by skin grafts in long-term tolerant animals and have found that anti-donor class I antibodies are not produced, even though the same animals produce both anti-class II and anti-third-party class I antibodies. PMID- 7886807 TI - Evidence that human cardiac allograft acceptance is associated with a decrease in donor-reactive helper T lymphocytes. AB - We have reported that acute cardiac allograft rejection is associated with increased numbers of donor-reactive helper T lymphocytes (HTL) in the peripheral blood of patients. Further, increased frequencies of circulating donor-reactive HTL may predict allograft rejection episodes diagnosed by endomyocardial biopsy. The present study evaluates the relationship between donor-reactive HTL and allograft "acceptance" in cardiac transplant recipients bearing long-term allografts (> 1 year). Patients were categorized as either long-term acceptors or persistent rejecters based on the number of rejection episodes and the ability to withdraw steroid therapy. Limiting dilution analysis for IL-2-producing HTL was utilized, with cadaver donor splenocytes as a source of donor alloantigens. Donor reactive HTL frequencies were determined from peripheral blood samples obtained before transplant, and at 1 month and 1 year after transplant. Individuals who accommodated their allografts and were withdrawn from steroid therapy had reduced numbers of donor-reactive HTL at 1 year after transplant as compared with earlier time points. Further, PBMC obtained from these individuals at 1 year after transplant responded weakly to donor alloantigens in a mixed lymphocyte response (MLR). This relationship between donor-reactive HTL and allograft accommodation was exemplified in a cardiac/liver transplant patient who was diagnosed with progressive multifocal leukoencephalopathy and removed from all immunosuppression. No subsequent rejection episodes were diagnosed. Donor reactive HTL were not detectable and this individual failed to mount an MLR to donor alloantigens. However, a vigorous donor-reactive response was observed when MLR cultures were supplemented with exogenous IL-2. Therefore, nonresponsiveness to the allograft appeared to be due to a deficit in IL-2 production. In contrast, patients who experienced persistent rejection episodes and required continued steroid therapy maintained large numbers of donor-reactive HTL at 1 year after transplant. PBMC from these individuals responded vigorously to donor alloantigens in an MLR. Hence, monitoring donor-reactive HTL may identify individuals who have accommodated their graft and may tolerate a reduction in immunosuppression. PMID- 7886808 TI - Intrathymic transplantation of allogeneic perinatal islets does not induce donor specific tolerance. PMID- 7886809 TI - An improved technique of thymectomy in the adult mouse. PMID- 7886810 TI - A percutaneous technique for venous return cannula insertion for veno-venous bypass in hepatic transplantation. PMID- 7886811 TI - Living unrelated renal transplantation for sickle cell nephropathy. PMID- 7886812 TI - Cloning by function: expression cloning in mammalian cells. PMID- 7886813 TI - Rodbell and Gilman win 1994 Nobel Prize for Physiology and Medicine. PMID- 7886814 TI - Complex interactions in 5-HT motor programmes. PMID- 7886815 TI - Indirect mechanism of drug transport by P-glycoprotein. PMID- 7886816 TI - Inflammatory mechanisms in Alzheimer's disease. AB - Alzheimer's disease is aetiologically heterogeneous, but the pathogenesis is often considered to be initiated by the deposition of amyloid fibrils, followed by neuritic tau pathology and neuronal death. A variety of inflammatory proteins has been identified in the brains of patients with Alzheimer's disease post mortem. In this article, Piet Eikelenboom and colleagues review evidence to suggest that the inflammatory processes are intimately involved in several crucial events in the pathological cascade. This suggests possibilities for the treatment of Alzheimer's disease with anti-inflammatory drugs. PMID- 7886817 TI - Do human atrial 5-HT4 receptors mediate arrhythmias? AB - Since their first description five years ago, knowledge about human atrial 5-HT4 receptors has increased considerably. Progress has been facilitated by the advent of selective antagonists with high affinity for human atrial 5-HT4 receptors. The receptors have been detected in both right and left atrium where they mediate increases in contractile force. Human sinoatrial 5-HT4 receptors may mediate the tachycardia caused by 5-HT and cisapride, and 5-HT elicits arrhythmias via 5-HT4 receptors in human atrium. In this article, Alberto Kaumann suggests that 5-HT may be involved in the genesis of atrial fibrillation and associated thromboembolic stroke and that both the arrhythmia and stroke could be prevented by inhibiting 5-HT4 receptors. PMID- 7886818 TI - Mechanisms of action of new antiepileptic drugs: rational design and serendipitous findings. AB - After years without any major breakthroughs in the treatment of epilepsy disorders, a new wave of antiepileptic drugs have become available to clinicians. Felbamate, gabapentin, lamotrigine and vigabatrin are among the most promising of this new generation of drugs and, when used as add-on therapy, provide some improvement in a significant number of patients suffering from previously refractory epilepsy whilst exhibiting a lower risk of unwanted side-effects than traditional antiepileptic drugs. In this article, Neil Upton reviews the recent discoveries that suggest these four new agents exert their antiepileptic properties by acting through diverse and often novel mechanisms, some of which are by design, and some of which are by chance. Also highlighted are examples of the most innovative mechanistic approaches currently being adopted to produce the next generation of antiepileptic drugs. PMID- 7886819 TI - K+ channel openers and suppression of airway hyperreactivity. AB - Openers of ATP-sensitive K+ channels (K(ATP) channels) can reduce obstruction to airflow by suppressing hyperreactivity of intact airways. This property can be observed in hyperreactive animals with doses that are insufficient to relax airway smooth muscle in situ in normal animals. Hence, the potency of openers of K(ATP) channels as inhibitors of bronchospasm is greater in hyperreactive than in normal animals. A closely analogous property has been described in clinical and laboratory studies of established anti-asthma drugs. Such findings raise the possibility that the therapeutic benefit of these drugs may depend upon an opening of K+ channels, either directly or indirectly. In this review, John Morley suggests that compounds that open K+ channels and impair expression of airway hyperreactivity in the absence of direct smooth muscle spasmolysis will provide a novel approach to symptomatic therapy in asthma. PMID- 7886820 TI - From UFC to PHC: five ways to integrate PHC so that it works. PMID- 7886821 TI - Assessment and management of common tibial injuries in a district hospital. PMID- 7886822 TI - Avoidable perinatal deaths in a rural hospital: strategies to improve quality of care. PMID- 7886823 TI - The contribution of counselling in hospital and home-based care in a small town and surrounding rural area in Zambia. PMID- 7886824 TI - Practical advice on field studies into hearing impairment in a developing country. PMID- 7886825 TI - Training traditional birth attendants for resuscitation of newborns. PMID- 7886826 TI - Jering-induced acute renal failure with blue urine. PMID- 7886827 TI - Fibrocalculous pancreatic disease. PMID- 7886828 TI - Chronic tuberculous cholecystitis. PMID- 7886829 TI - How to do it: neonatal exchange blood transfusion. PMID- 7886830 TI - An innovative method of tourniquet application in proximal lower limb surgery. PMID- 7886831 TI - A method of taking Thiersch grafts using a scalpel blade. PMID- 7886832 TI - Humidification after tracheostomy: simple techniques. PMID- 7886833 TI - Retrospective study of treatment of amoebic liver abscesses with and without aspiration. PMID- 7886834 TI - Salmonella typhi. PMID- 7886836 TI - Tetanus--adults too need proper protection. PMID- 7886835 TI - The partograph: is it worth including the latent phase? PMID- 7886837 TI - Antimicrobial susceptibility of Neisseria gonorrhoeae, the essential drug list, and HIV/AIDS control. PMID- 7886838 TI - Supracondylar fractures in children. PMID- 7886839 TI - An unusual cause of difficult intubation. PMID- 7886840 TI - Putting the Madura foot in it! PMID- 7886841 TI - Bacterial meningitis in developing countries. PMID- 7886842 TI - Upper gastrointestinal endoscopy in an urban hospital in northern Nigeria: association of presenting features with endoscopic findings. AB - In 326 fibreoptic upper gastrointestinal (GI) endoscopies performed in Evangel Hospital (Jos, Nigeria), pathology was found in 210 patients, and of a major nature such as peptic ulcer disease or cancer in 129 of these. The three most useful features to predict the presence of major pathology were epigastric tenderness (the single most useful feature), loss of weight and epigastric pain of a burning nature. These features were selected by stepwise discriminant analysis, which also led to the conclusion that the presence of at least two of these three features is an even more powerful predictor of major pathology. PMID- 7886843 TI - A new Doppler imaging measurement in aortic stenosis: the contour length of the jet origin flow area. Relationships between both, with usual Doppler data and left ventricular hypertrophy. AB - Planimetry of stenotic aortic jet origin flow areas was performed using transthoracic Doppler imaging, with measurement of the contour length of flow areas and calculation of a contour/area (C/A) Doppler ratio on a group of 75 patients with aortic stenosis ranging from 0.27 to 2.44 cm2. The purpose was to study correlations of these data with the usual Doppler data and with left ventricular hypertrophy. The "r" coefficient between planimetered flow areas and those calculated by the continuity equation method was 0.89. Mean values (SD) of data were: areas: (planimetry) 1.00 +/- 0.53 cm2, (continuity equation) 0.91 +/- 0.42 cm2, contours: 5.6 +/- 1.6 cm, C/A: 0.66 +/- 0.25, maximal and mean pressure gradients: 68 +/- 34 and 37 +/- 21 mmHg, left ventricular hypertrophy: 138 +/- 30 g/m2 BSA (vs. 100 +/- 18 in normals). All values except age, gender and BSA, differed significantly (p < 0.001) between areas below or over 0.85 cm2. Other correlations between parameters were significant (p < 0.01 to 0.001), but with lower "r" coefficients due to widely scattered individual values. Contours increased much less rapidly than areas did, and were correlated with left ventricular hypertrophy only when coupled in the C/A ratio, with a higher "r" coefficient (0.62) than areas alone (0.52). Study of both areas and contours helps to approach the geometry of the orifice. This suggests that the individual geometry of the stenosis might weigh on the left ventricular mass growth, as an associated factor for a given decrease in stenotic area. PMID- 7886844 TI - Relationships between contour and/or contour/area ratio at Doppler and left ventricular hypertrophy in patients with significant aortic stenosis. AB - Planimetry of the stenotic flow areas using Doppler imaging of jet origin was performed, together with the measurement of their contour and a calculated contour/area (C/A) Doppler ratio, on 38 adult patients with significant aortic stenosis (0.27 to 0.85 cm2). Echo measurements of left ventricular hypertrophy (LVH) were also performed to study the differences in LVH according to the areas, even in case of smaller areas. This led to lower mean values of LVH (p < 0.001) in this group, and to a correlation coefficient at 0.18. The smallest areas were generally rounded and had a high C/A ratio. Contour was regular in half of areas over 0.5 cm2. It increased less rapidly than areas increased, leading to a decreased C/A. The other half, of a similar range of sizes, had a markedly increased irregular contour, entailing a C/A > 0.8. The highest mean value in LVH was found in this subgroup. Correlation coefficients vs. LVH were 0.43 for contour, and 0.32 for C/A ratio. Diagnostic reliability of a C/A > 0.8 for an LVH > 150 g/m2 BSA ranged from 55 to 70%. In conclusion, the study suggests that contour length weighs on LVH development when stenoses are significant, and should be coupled with area measurements. Figures also suggest that other factors intervene, requiring further study. PMID- 7886846 TI - Automated method for characterization of diastolic transmitral Doppler velocity contours: late atrial filling. AB - We develop an automated method of characterizing the late atrial filling phase of diastole by fitting a kinematic model for diastolic filling to the clinical Doppler A-wave contour. The result is a set of model parameters which completely characterizes the contour. We have previously derived a parameterized diastolic filling (PDF) model, which predicts the time-dependent transmitral blood flow velocity obtained by Doppler echocardiography. An automated method to determine the PDF model parameters for early rapid filling from the clinical Doppler E-wave has also been developed and validated. The method consists of digitizing the acoustic Doppler waveform, recreating the Doppler velocity profile, extracting the maximum velocity envelope, and fitting the PDF model for early filling to the envelope. In the current work, we apply the same general approach for PDF parameter determination for the late atrial filling phase of diastole. To assess the presence and significance of near-degeneracies in the model parameter set, numerical experiments (consisting of fitting the model to a model-generated contour to which Gaussian noise was added) were performed. These revealed a two dimensional degeneracy in four-dimensional parameter space which could be removed by using two kinematic simplifications: critical damping and resonant forcing. We show that these degeneracy-eliminating approximations do not limit the ability of the model to predict clinical A-wave contours. PMID- 7886845 TI - Color Doppler flow criteria of breast lesions. AB - Color Doppler technique has been available for several years. The sensitivity of the equipment has improved and allows for assessment of tumor vascularity. We investigated multiple parameters in 258 patients, with 176 benign and 82 malignant lesions to define characteristic flow criteria. Median (25-75% quartiles) and p-values are given for benign vs. malignant lesions. Number of tumor vessels: 2 (1-2) vs. 8 (5-14), p < 0.0001; mean peak systolic flow velocity: 11.1 cm/s (6.4-14.9) vs. 18.8 cm/s (13.7-25.1), p < 0.0001; maximum flow velocity: 12.5 cm/s (6.7-18) vs. 32.5 cm/s (22.5-47.3), p < 0.0001; sum of all systolic flow velocities: 18.9 cm/s (7-34.2) vs. 147 cm/s (71.3-266.7), p < 0.0001; minimum systolic flow velocity: 8.9 cm/s (5.4-12.1) vs. 9 cm/s (6.3 11.3), p > 0.05; average resistance index (RI): 0.68 (0.58-0.72) vs. 0.75 (0.67 0.81), p > 0.05; maximum RI: 0.71 (0.65-0.78) vs. 0.88 (0.78-0.99), p < 0.0001; minimum RI: 0.64 (0.57-0.68) vs. 0.64 (0.53-0.71), p > 0.05; average A/B ratio: 3.1 (2.7-3.7) vs. 4.3 (3.2-7.7), p < 0.0001; maximum A/B ratio: 3.4 (2.9-4.6) vs. 8.4 (4.5-9.9), p < 0.0001; minimum A/B ratio: 2.8 (2.3-3.2) vs. 2.9 (2.2-3.5), p > 0.05. The data analysis shows that flow resistance in malignancies is increased. This is in contrast to gynecological malignancies, where an increased diastolic flow indicates that flow resistance is decreased. PMID- 7886847 TI - The reliability of computer analysis of ultrasonographic prostate images: the influence of inconsistent histopathology. AB - This article describes a method to investigate the influence of inconsistent histopathology during the development of tissue discrimination algorithms. Review of the pathology is performed on the biopsies used as training set of a computer system for cancer detection in ultrasonographic prostate images. The influence of the discrepancies found between independent pathologists on the discriminating power of the system is investigated. A high diagnostic consistency in histopathology concerning only the categories malignant and nonmalignant is found. Therefore, review of the pathology does not significantly influence the results of tissue discrimination algorithms for cancer detection. However a high interobserver variability is obtained in the differentiation between more histology classes. PMID- 7886848 TI - Lesion detection in simulated elastographic and echographic images: a psychophysical study. AB - The image quality of two ultrasonic imaging techniques was studied: conventional echography and the recently introduced elastography. The image quality was assessed by estimating the detectability of disc-shaped lesions of various sizes and contrast levels. The study was designed to verify the hypothesis that elastograms could show lesions at a higher subjective and objective level of detectability than echograms of the same object contrast. This hypothesis was adopted because homogeneous elastograms can present a higher point signal-to noise ratio than uniform echograms. Both elastograms and echograms were generated by two-dimensional (2D) simulations. The subjective assessment was performed by psychophysical experiments using the staircase up-down method. The threshold contrast of detection for both modalities was determined at different diameters of the disc-shaped lesion. These values were used to construct the contrast detail curves for both techniques. For identical object contrasts, elastography was found to have significantly higher detectability at all lesion diameters considered. The contrast thresholds were also used for an objective evaluation with the lesion signal-to-noise ratio. The objective measure evaluated at the subjective threshold of detection for both modalities was not found to be identical, nor constant over the range of lesion diameters as expected. PMID- 7886849 TI - Aortic Doppler velocity measurement and cardiac function in the fetal lamb. AB - Aortic haemodynamic parameters, and Doppler waveforms in particular, were investigated in acute experiments with fetal lambs. Cardiovascular changes were produced by central infusion of the drugs esmolol and dopamine. Pulsed Doppler waveforms were obtained from the descending thoracic aorta, simultaneous with recordings of pulsatile aortic volume flow rate, diameter and blood pressure. The relation between Doppler-derived velocities and the corresponding full vessel lumen velocities was shown to be fairly linear and consistent across different animals. The aortic volume flow per beat decreased with esmolol (p < 0.003, repeated measures ANOVA); the Doppler and vessel lumen mean velocities also decreased, whether measured only at peak systole or over the full cardiac cycle (at most p < 0.003). With dopamine the aortic flow per beat increased (p < 0.001), as did the Doppler and vessel lumen mean velocities (at most p < 0.02). An inverse relation between the aortic flow per beat and the peripheral resistance was observed. To identify inotropic changes in the presence of vascular effects, a theoretical model based on cardiac power output changes was implemented. The data were divided into three groups, according to whether the model did or did not identify a definite inotropic effect (positive or negative). The Doppler velocity changes for these three groups were different (p < 0.0001). The mean Doppler velocity increased by 7 cm s-1 in the positive inotropic effect group, and decreased by 4 cm s-1 in the negative group. The aortic flow parameters of the human fetus are very similar to those of the fetal lamb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886851 TI - Theoretical estimation of the temperature dependence of backscattered ultrasonic power for noninvasive thermometry. AB - The backscattered signal received from an insonified volume of tissue depends on tissue properties, such as attenuation, velocity, density, and backscatter coefficient and on the characteristics of the transducer at the insonified volume. Analysis of scattering in response to a burst of insonification showed that the temperature dependence of backscattered power was dominated by the effect of temperature on the backscatter coefficient. The temperature dependence of attenuation had a small effect on backscattered power. Backscattered power was independent of effects of temperature on velocity. These results were seen in the analysis of two types of inhomogeneity: 1) an aqueous scatterer in a water-based medium and 2) a lipid-based scatterer in the same water-based medium. The temperature dependence of the backscatter coefficient was inferred assuming that the backscatter coefficient was proportional to the scattering cross-section of a small scatterer. Backscattered power increased nearly logarithmically with temperature over the range from 37 degrees to 50 degrees C. Our model predicted a change of 5 dB for the lipid scatterer and a change of up to 3 db for the aqueous based scatterer over that temperature range. For situations in which temperature dependence of the backscattered power can be calibrated, it may be possible to use the backscattered power level to track temperature distributions in tissue. PMID- 7886850 TI - A computer model for simulating ultrasonic scattering in biological tissues with high scatterer concentration. AB - Scattering of ultrasonic waves by biological tissues at different scatterer concentrations is investigated using one- and two-dimensional computer simulation models. The backscattered power as a function of scatterer concentrations is calculated using two types of incident waves, a Gaussian shaped pulse and a continuous wave (CW). The simulation results are in good agreement with the Percus-Yevick packing theory within the scatterer concentrations, from 0% to 100% in one-dimensional (1D) space, and 0% to 46% in two-dimensional (2D) space. In all cases, the simulation results from a pulsed incident wave show a much smaller standard deviation (SD) than those from an incident CW. The simulation can serve as a useful tool to verify scattering theories, simulate different experimental conditions, and to investigate the interaction between the scatterer properties and the scattering of ultrasonic waves. More importantly, the 2D simulation procedure serves as an initial step toward the final realization of a true three dimensional (3D) simulation of ultrasonic scattering in biological tissues. PMID- 7886852 TI - 3D ultrasonic image feature localization based on magnetic scanhead tracking: in vitro calibration and validation. AB - The basis of a three-dimensional (3D) ultrasound imaging system was constructed from a commercially available magnetometer-based position and orientation measurement (POM) device, a standard B-Mode ultrasound instrument and a personal computer. To evaluate the system's performance, a novel method was devised using an iterative, least-squares technique to simultaneously determine the system's calibration parameters and measure its precision in locating points in three dimensional space. When tested separately, the POM system located single points with a root mean squared (RMS) uncertainty of from 1.4 mm to 3.2 mm over the 610 mm working radius of the system. When combined with the ultrasound instrument, the RMS uncertainty in locating point targets varied from 2.1 mm to 3.5 mm. These results establish the lower limits of variability to be expected from this system when locating fiducial anatomical landmarks for repeated examinations of the same region of the body, and when making numerical 3D reconstructions from multiple planar images. PMID- 7886853 TI - Assessment of colour Doppler tissue imaging using test-phantoms. AB - An investigation has been carried out on the velocity resolution, spatial resolution and accuracy of Doppler images as part of a study into the Doppler display of cardiac tissue motion. Test-phantoms were designed to perform this work and images were captured on a computer. The characteristics of the phantom images and of the image capture process were studied. The smallest spatial detail that was observed in the Doppler image was 3 mm by 3 mm. Doppler receive gain and Doppler ensemble size both affected velocity resolution. Different target materials gave different measures for velocity resolution. This could be related to the different back-scatter intensities of the materials. PMID- 7886854 TI - Subsample volume processing of Doppler ultrasound signals. AB - Processing of Doppler signals produced by pulsed Doppler systems is based on the assumption that the phase of the received high frequency ultrasound signals changes linearly with depth. However, the random spatial distribution of scatterers is not in accordance with this basic assumption. Consequently, averaging of the demodulated signal over an observation window, covering a few periods of the received signal, does not improve the estimate for the instantaneous quadrature components of the Doppler signal originating from a given depth. Hence, the accuracy of the Doppler velocity estimate is independent of the length of the observation window employed. However, splitting the observation window in subsample volumes, each with a length of one period at the emission frequency, and combining the Doppler signals of the subsample volumes at the last stage of signal processing, i.e., mean Doppler frequency estimation using the autocorrelation technique, results in a considerable reduction of the variance of the velocity estimate. Using a computer simulation of the signal processing involved, it is demonstrated that with subsample volume processing the variance of the velocity estimate attains the same variance as is expected for the RF cross correlation technique. PMID- 7886855 TI - Ultrasonic spectroscopy of the porcine eye lens. AB - The purpose of the work is to measure and study the acoustic characteristics of the porcine eye lens and find correlations with chemical and optical parameters, obtained from literature. Ultrasonic spectroscopy was performed by using a scanning acoustic macroscope (frequency 20 MHz, resolution 150 microns). The transducer performed a two-dimensional scan over a central slice (1 mm thickness) of porcine lens (number of lenses = 10). A double transmission pulse-echo method was used to acquire the ultrasonic data from the lens. Two-dimensional images were reconstructed of the local ultrasound velocity and the frequency-dependent ultrasound attenuation. Axial and equatorial profiles of these parameters were calculated from the images. The acoustic parameters are not constant, but show a systematic dependence on the location within the lens. The profiles of the acoustic parameters are similar in shape to profiles of the protein and water contents of eye lens and to the profiles of the optical refractive index. A thorough quantitative correlation study is indicated, which should be based on detailed protein content data in porcine lenses. PMID- 7886856 TI - Ultrasound propagation speed in arthritic synovial tissue. AB - Ultrasonic properties of knee synovial tissues destroyed by arthritis were studied by analysing 40 tissue specimens from 21 patients using an ultrasound echo meter and an optical microscope. The idea was to compare pathological findings to ultrasound propagation speeds, and to try to find any relation between them. The fresh specimens were first measured by the echo meter to collect data for statistical calculations of the propagation speed vs. different pathological properties. Before pathological studies, the specimens were fixed in formalin solution. The connective and fat tissues were evaluated within a resolution of 5% and expressed in percentages (0-100%). Inflammatory cells, edema and villus formation were also evaluated. As results, we obtained several charts of ultrasound propagation speed and their trends in the function of different properties. It could be seen that the trend of the propagation speed increased from 1515 m/s to 1565 m/s when the percentage amount of connective tissue increased from 30% to 90%. The trend of the speed decreased from 1560 m/s to 1480 m/s when the share of fat tissue increased from 0 to 60%. The same phenomenon is already well known from some other tissues. A special new result was that the speed varied in a remarkable range of 1490-1660 m/s in samples of 0% fat and high connective tissue content. The overall average of the ultrasound propagation speed in the specimens was 1548 m/s, and the average of the standard deviations of measurements (each specimen was measured at least twice) of each tissue specimen was 8.3 m/s. PMID- 7886857 TI - A test of the hypothesis that diagnostic ultrasound disrupts myelination in neonatal rats. AB - Neonatal rats were exposed or sham exposed for 30 min to pulsed ultrasound [2.25 MHz carrier frequency, 1 microsecond pulse length, 50 Hz pulse repetition frequency (PRF), 50 W/cm2 Imax, 2 mW/cm2 ITA], euthanised and prepared for electron microscopic analysis of the nodes of Ranvier of the dorsal and ventral roots of the spinal cord. There was also a cage control. All materials were processed and scored blindly, evaluating whether perinodal myelin was normal. Rats from all regimens had areas of disrupted myelination. There was no statistically significant difference among the regimens for absence of myelination. The results did not confirm an earlier report that diagnostic ultrasound disrupts myelination in neonatal rats. PMID- 7886859 TI - Members. American Ophthalmological Society. PMID- 7886858 TI - Pulse duration and peak intensity during focused ultrasound surgery: theoretical and experimental effects in rabbit brain in vivo. AB - The goal of this study was to establish the exposure parameters that will generate predictable thermally induced lesions in brain. In addition, the accuracy of a theoretical model for prediction of the lesion size was tested. To do this, 160 adult rabbits were sonicated (frequency 0.936 and 1.72 MHz) and then sacrificed at various intervals after the sonications. The results showed that predictable thermal lesions could be induced if the exposure durations were between 0.5 and 2 s. Dimensions of the necrosed tissue volume were roughly predictable by the theoretical calculations based on purely thermal effects. Shorter sonications required higher intensities (above 3700 W cm-2 at 1.72 MHz) resulting in mechanical effects with extensive vascular damage. Lesion size varied more at longer exposures (5 and 10 s), perhaps due to the increased effect of tissue perfusion. As a conclusion, focused ultrasound can be used for destruction of tissues deep in brain without causing undesirable mechanical effects, if the exposure parameters are selected properly. PMID- 7886860 TI - Progressive increase in the angle of deviation in congenital esotropia. AB - The majority of patients with congenital esotropia in this consecutive series of 41 patients showed an increase in the angle of deviation when followed over an average of 3 months. The ages at the initial measurement and surgery, the cycloplegic refraction, and the clinical response to patching could not be used to identify those patients with a progressive increase in the quantity of the deviation. It was found, however, that if the preliminary surgical plan was adjusted (as it was in the majority of the patients in this series) to reflect the latest measurements obtained the day before surgery, a relatively high percentage of patients (90%) could be found to have achieved satisfactory alignment by the 6-week postoperative visit. PMID- 7886861 TI - A clinicopathologic study of posterior polymorphous dystrophy:implications for pathogenetic mechanism of the associated glaucoma. PMID- 7886862 TI - The blinding mechanisms of incontinentia pigmenti. AB - Five case histories illustrate the disabling visual diseases caused by retinal and cerebral infarction in incontinentia pigmenti. Cortical blindness was definitely present in one baby, who had bilateral absence of light perception, and was probably present in a second infant also. Retinal detachment occurred in three eyes of three patients, one of whom had spontaneous reattachment. In a second patient, a partial tractional retinal detachment progressed within 4 months during infancy to a total, inoperable, retrolental, white fibrovascular mass mimicking stage 5 retinopathy of prematurity. Phthisis bulbi resulted. In a third patient, a localized tractional retinal detachment originated at the nonperfused macula and extended over a 7-month period to the ora serrata. Preretinal neovascularization waxed and waned in these and other patients. Abnormalities of the macula were pronounced but were sometimes difficult to detect. Their severity and relative frequency have not been previously described in detail. Abnormalities included blunting or absence of the foveal pit and absence of the normal foveal avascular zone. One patient at 12 days of age had an infarcted macula with a cherry-red spot. Similar episodes may have occurred in other children and would be sufficient to explain the appearance of macular abnormalities and otherwise unexplainable poor visual acuity in older individuals. Well-focused macular angiography appears to be highly useful in explaining visual disability due to abnormal foveal anatomy and function. Optic atrophy occurred in several eyes. Its pathogenesis may be multifactorial. Further research is necessary to elucidate the mechanisms of vascular closure in the retina as well as the pathogenesis of destructive encephalopathy in this exceptionally severe disease. Valid therapeutic possibilities may then become more obvious than they are at present. It is possible that the retina and brain undergo similar disease processes in incontinentia pigmenti. PMID- 7886863 TI - Antibiotic prophylaxis in corneal storage media. PMID- 7886864 TI - Retrospective study of hyperabnormal (supranormal) electroretinographic responses in 104 patients. PMID- 7886865 TI - Excimer laser photorefractive keratectomy for myopia: a single surgeon best-case analysis. PMID- 7886866 TI - Excimer laser treatment for high and extreme myopia. PMID- 7886867 TI - Noncontact transscleral Nd:YAG cyclophotocoagulation: a long-term follow-up of 500 patients. AB - Long-term experience with transscleral cyclophotocoagulation in 500 patients suggests that this operation is the cyclodestructive procedure of choice. It offers a reasonable surgical option in the high-risk glaucoma population, which includes patients with neovascular glaucoma, glaucomas with active uveitis, glaucomas in aphakia or pseudophakia, and other cases in which filtering surgery has failed or is felt to have a low chance for success. Satisfactory intraocular pressure reduction was achieved in 62% of the patients with one treatment session. After one or more repeated procedures in 21% of the study group, the final intraocular pressure was below baseline in 94%, with a mean final reduction of 24 mm Hg, which was judged to be adequate for 87% of the patients. However, visual loss remains a significant postoperative complication, with some degree of reduced vision occurring in 39% of the study population. Patients with neovascular glaucoma had the greatest percentage of visual loss at 46%, compared with 34% and 38% for patients with glaucomas in pseudophakia and aphakia, respectively. While it is hard to know how many of these cases of visual loss were a direct result of the cyclophotocoagulation, the procedure should be used with caution in eyes with a potential for good central vision. Further study is needed to determine the relative indications for transcleral cyclophotocoagulation and the various operations to increase aqueous outflow in the management of patients in the high-risk glaucoma population. PMID- 7886868 TI - Are sex hormones associated with age-related maculopathy in women? The Beaver Dam Eye Study. PMID- 7886869 TI - Photocoagulation of drusen-related macular degeneration: a long-term outcome. PMID- 7886870 TI - The management of wound-related complications in pars plana vitrectomy. PMID- 7886871 TI - Prospective investigation of the effectiveness of intraoperative adjustable sutures for correction of strabismus. PMID- 7886872 TI - Consequences of retinal image clarity versus occlusion (absent) versus diffusion. AB - A series of clinical questions and stated hypotheses suggested in the pre-1960s regarding the differences between stimuli of occlusion and diffusion are presented (Part I) and are answered and confirmed by a series of experiments and data in animals and humans. A diffusion stimulus is extremely destructive to development of the acuity system in an eye per se (as well as producing myopia), and a unilateral diffusion stimulus is also destructive to development of the binocular system. Real occlusion is a no-stimulus condition that can be used to preserve normal acuity and binocular development, and as a delay tactic to successfully counteract the detrimental effect of diffusion. Binocular input differences (especially if one is a diffusion stimulus) are a major cause of strabismus in both the immature and mature binocular systems. The hypothesis was proposed that preoperative full-time alternate occlusion in infantile esotropia enhanced the binocularity outcome (for which supportive experimental data in animals and humans from our laboratories are discussed in Part III). Animal experiments during the 1960s and 1970s are reviewed relative to the confusion and conflict generated (Part II), since many of these experiments were based on the false assumptions that the unilateral eyelid closure model was a no-stimulus condition (because of the small amount of light transmitted). In fact, it was a worst-case severe stimulus with both monocular and binocular detrimental consequences. And the unilateral eyelid closure model usually produced either undetected or ignored strabismus in the animal experiments, with such strabismus severely compounding the detrimental effects of the eyelid closure model. Further confusion was added by the amblyopia therapeutic model in animals of "reverse eyelid occlusion" (which was really reverse diffusion) and which the author maintains was a gross distortion of the clinician's real occlusive patch over the better eye in the therapy of amblyopia of the poorer eye. These confusions and conflicts were at variance with long-standing clinical percepts. Part III provides data from the series of animal and human experiments from our laboratories at Smith-Kettlewell Eye Research Institute, which clarify the confusion and conflicts of some of the animal experiments described. Our data support the original hypotheses (Part I) enabling the clinician to use occlusion measures in selected patients to expand the therapeutic timing options and to improve visual outcomes. Binocular system outcomes are shown to be improved by our recent data in animal and human experiments, thus supporting the beneficial sensory effects of preoperative full-time alternate occlusion regimes in infantile esotropia. PMID- 7886873 TI - The effects of glaucoma filtering surgery on the variability of diurnal intraocular pressure. AB - The results of this study indicate that filtration surgery reduces the mean diurnal IOP, the range of diurnal variation, and the day-to-day variability. The effect on the range is proportionally greater than on the other two parameters. Further study will be required to determine whether this selective effect makes surgical reduction of IOP any more effective in the prevention of further glaucomatous visual field damage than other therapeutic methods that lower mean IOP to the same degree. PMID- 7886875 TI - The epidemiology of epiretinal membranes. PMID- 7886874 TI - Transgenic models of retinoblastoma: what they tell us about its cause and treatment. PMID- 7886876 TI - Retinal and choroidal biopsy in intraocular inflammation: a clinicopathologi study. PMID- 7886877 TI - 'Unilateral cone dystrophy': ERG changes implicate abnormal signaling by hyperpolarizing bipolar and/or horizontal cells. AB - The two cases described here appear to represent the infrequently reported entity of "unilateral cone (cone-rod) dystrophy." Both cases give the suggestion that daylight vision can be affected by abnormalities in visual signals in the proximal retina, after they leave the cone photoreceptors themselves. The ERG waveform changes in these two cases are consistent with a deficit in signaling by the hyperpolarizing bipolar cells, and the complaint of abnormal color perception in both cases presented here raises the possibility that the OFF-pathway through hyperpolarizing bipolar cells may be important for color processing. PMID- 7886880 TI - Video vision development assessment (VVDA): combining the Bruckner test with eccentric photorefraction for dynamic identification of amblyogenic factors in infants and children. PMID- 7886878 TI - The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. AB - Among incident cases of GO in Olmsted County, Minnesota: GO affected females six times more frequently than males (86% versus 14% of cases, respectively). The age adjusted incidence rate was 16 cases per 100,000 population per year for females and 2.9 cases per 100,000 population for males. The peak incidence rates were bimodal, occurring in the age groups 40 to 44 years and 60 to 64 years in females and 45 to 49 years and 65 to 69 years in males. Among patients with GO, approximately 90% had Graves' hyperthyroidism, 1% had primary hypothyroidism, 3% had Hashimoto's thyroiditis, and 5% were euthyroid. Eyelid retraction was the most common ophthalmic feature of autoimmune thyroid disease, being present either unilaterally or bilaterally in more than 90% of patients at some point in their clinical course. Exophthalmos of one or both eyes affected approximately 60% of patients, restrictive extraocular myopathy was apparent in about 40% of patients, and optic nerve dysfunction occurred in either one or both eyes in 6% of patients with autoimmune thyroid disease. Only 5% of patients had the complete constellation of classic findings: eyelid retraction, exophthalmos, optic nerve dysfunction, extraocular muscle involvement, and hyperthyroidism. Upper eyelid retraction, either unilateral or bilateral, was documented in approximately 75% of patients at the time of diagnosis of GO. Lid lag also was a frequent early sign, being present either unilaterally or bilaterally in 50% of patients at the initial examination. At the time of diagnosis of GO, the most frequent ocular symptom was pain or discomfort, which affected 30% of patients. Some degree of diplopia was noted by approximately 17% of patients, lacrimation or photophobia was present in about 15% to 20% of patients, and 7.5% of patients complained of blurred vision. Decreased vision attributable to optic neuropathy was present in less than 2% of eyes at the time of diagnosis of GO. Thyroid dermopathy and acropachy accompanied GO in approximately 4% and 1% of patients, respectively. Myasthenia gravis occurred in less than 1% of patients. Superior limbic keratoconjunctivitis was documented in less than 4% of patients. The median age at the time of diagnosis of GO was 43 years (range, 8 to 88). Among patients with hyperthyroidism, 61% developed ophthalmopathy within 1 year of the onset of thyrotoxicosis. Symptoms and signs for which statistically significant changes occurred between the initial and final examinations included lacrimation, pain or ocular discomfort, photophobia, eyelid retraction, lid lag, eyelid fullness, conjunctival injection, chemosis, and exophthalmos.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7886879 TI - Clinical evaluation of the optic nerve in glaucoma. PMID- 7886882 TI - Heterogeneous length and in-series arrangement of orbicularis oculi muscle: individual myofibers do not extend the length of the eyelid. PMID- 7886881 TI - Giant papillary conjunctivitis. AB - Giant papillary conjunctivitis is a syndrome found frequently as a complication of contact lenses. Many variables can affect the onset and severity of the presenting signs and symptoms. Rigid gas permeable contact lenses appear to result in less severe signs and symptoms, with a longer time before the development of giant papillary conjunctivitis. Nonionic, low-water-content soft contact lenses tend to produce less severe signs and symptoms than ionic, low water-content soft contact lenses. Enzymatic treatment appears to lessen the severity of signs and symptoms. The association of an allergy appears to play a role in the onset of the severity of the signs and symptoms but does not appear to affect the final ability of the individual to wear contact lenses. Using multiple treatment options, such as changing the polymer to a glyceryl methyl methacrylate or a rigid lens, or utilizing a soft lens on a frequent-replacement basis, can result in a success rate of over 90%. In individuals who still have a return of symptoms, the use of topical mast cell stabilizers or a nonsteroidal anti-inflammatory drug as an adjunctive therapy offers the added possibility of keeping these patients in contact lenses. PMID- 7886883 TI - The natural history of the first clinically visible features of diabetic retinopathy. AB - Microaneurysms are the first features of human diabetic retinopathy that can be detected with common clinical techniques. These are found, most often, in photographic field 2 (that is, an area occupying 30 degrees of the ocular fundus centered on the middle of the macula). After the first microaneurysms develop, there will be a tendency for more to appear; however, over time many of the original microaneurysms will become no longer visible with clinical techniques, while other, newer, microaneurysms mature. After the onset of microaneurysms, several years may pass before any other diabetic retinopathic lesions develop. Lesions other than microaneurysms were uncommon in this study; the following is a list in decreasing frequency: retinal hemorrhages, soft exudates, IRMA, hard exudates, and venous beading. During the 4 years of this study, there were no other diabetic retinopathic lesions detected. The duration of insulin-dependent diabetes mellitus was related to the rate of change in microaneurysm counts. The age and sex of patients did not affect this rate of change. The accuracy of metabolic control, as determined by glycosylated hemoglobin levels, may influence this rate of change; however, this was detected only at the extremes of measurement in this study. The equipment available to most ophthalmologists can detect the earliest clinical aspects of diabetic retinopathy. These features can be quantified in a reproducible manner with standardized photographic techniques to permit satisfactory data analysis. PMID- 7886884 TI - A twin study on age-related macular degeneration. AB - A prospective twin study on age-related macular degeneration (AMD) recruited 83 monozygotic pairs, 28 dizygotic pairs, and one triplet set from 1986 through 1993. Zygosity was determined by genetic testing of red cell markers, HLA antigens, or specific DNA loci. There were no twin pairs in which I collected data on only one twin. To decrease ascertainment bias, after 1991 the recruitment notice did not mention AMD, and I did not ask about a history of eye disease before the eye examination. Because of this, twin pairs recruited from 1986 through 1991 were statistically analyzed separately from those after January 1, 1992. From 1986 through 1991, 23 twin pairs were recruited; 11 monozygotic and 2 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 9 monozygotic pairs with AMD were all concordant, and 1 dizygotic pair was discordant for basal laminar drusen. The concordance rate of AMD did not differ significantly between monozygotic and dizygotic twin pairs (P = .10) for 1986 through 1991. In 1992 and 1993, 88 twin pairs and one triplet set were recruited; 49 monozygotic and 19 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 14 monozygotic pairs with AMD were all concordant, and 2 of 7 dizygotic pairs were concordant for AMD. The nonidentical triplets (1 with and 2 without AMD) were categorized as one of the discordant dizygotic pairs in the statistical evaluation. In nontwin age-matched (within 2 or 5 years of age) or age- and sex-matched sibling pairs the concordance rate of AMD ranged from 16% to 25%. The concordance rate of AMD was significantly higher in monozygotic than in dizygotic twins (P = .001) for 1992 and 1993. The concordance rate was higher for monozygotic twin pairs recruited in 1992 and 1993 than in any of the four subsets of nontwin age-method or age- and sex-matched sibling pairs (P < .0001). Overall, from 1986 through 1993, 23 of 23 monozygotic and 2 of 8 dizygotic twin pairs were concordant for AMD; this included the one dizygotic pair which was discordant for basal laminar drusen. The data of this study strongly suggest a genetic predisposition to AMD. PMID- 7886886 TI - Agriculture Committee rejects 'disease time-bomb' scenario. PMID- 7886887 TI - A new method of paternity testing for dogs, based on microsatellite sequences. AB - Microsatellite sequences, like minisatellites, belong to a class of polymorphic DNA that is commonly found in mammalian DNA. Although they vary significantly less in a population of animals than minisatellites, they have potential for use in paternity disputes. However, their inherently lower variability together with the more genetically homogeneous nature of pedigree dogs due to inbreeding (line breeding), raised doubts about their effectiveness for paternity tests. This paper demonstrates that canine microsatellites provide an adequate basis for assigning paternity in pedigree breeds. The system presented is more straightforward to perform and interpret than that based on canine minisatellites (DNA 'fingerprinting') and requires as little as 0.1 ml of blood. PMID- 7886888 TI - Pharmacokinetics of oxytetracycline in goats: modifications induced by a long acting formulation. AB - The pharmacokinetics of oxytetracycline were studied in goats, after the intravenous and intramuscular injection of a conventional and long-acting formulation. The antibiotic was distributed according to an open two-compartment model. The apparent volume of distribution (Vz) and the central compartment volume (Vc) were 1.443 litres/kg and 0.453 litre/kg, respectively, and the total body clearance was 0.156 litre/kg/hour. The mean half-lives (T1/2 lambda z) of the conventional formulation after intravenous and intramuscular administration were six hours 28 minutes and 10 hours 38 minutes, respectively, whereas the long acting formulation had half-lives of six hours 36 seconds and 29 hours, respectively, after intravenous and intramuscular injection. From the results of these single administrations two intramuscular dosage regimens can be proposed that achieve minimum concentrations of over 0.5 mg/litre (the minimum inhibitory concentration for most susceptible pathogens): with the conventional formulation by administering an initial dose of 10 mg/kg and a maintenance dose of 8.5 mg/kg every 24 hours, and with the long-acting formulation by administering an initial dose of 20 mg/kg and a maintenance dose of 14 mg/kg every 48 hours. PMID- 7886889 TI - Bioavailability of different forms of amoxycillin administered orally to dogs. AB - Amoxycillin was administered to six dogs intravenously (as the sodium salt at 20 mg/kg bodyweight) and orally (as the trihydrate at 20 mg/kg). The oral treatments followed a Latin square pattern, each dog receiving amoxycillin as a 60 ml suspension by stomach tube, or as 3 ml of drops or in the form of tablets. The concentration of the drug in the plasma was measured microbiologically and its pharmacokinetic parameters were calculated by the use of statistical moments. After intravenous administration the mean +/- sd apparent volume of distribution was 0.312 +/- 0.102 litre/kg, the steady state rate of clearance was 3.4 +/- 1.1 ml/min/kg and the mean residence time was 1.6 +/- 0.4 hours. After oral administration the liquid forms of the drug tended to be more readily absorbed than the tablets, as indicated by their higher bioavailabilities (suspension 76.8 +/- 16.7 per cent, drops 68.2 +/- 25.8 per cent, tablets 64.2 +/- 17.9 per cent). However, the differences between their pharmacokinetic parameters were not statistically significant. The respective values of Cmax for the tablets, drops and suspension were 18.6 +/- 5.3 micrograms/ml, 18.1 +/- 2.4 micrograms/ml and 20.7 +/- 2.2 micrograms/ml, of tmax 2.0 +/- 1.0 hours, 1.4 +/- 0.6 hours and 1.4 +/- 0.5 hours and of the AUC 69.5 +/- 22.5 micrograms/ml hours, 71.8 +/- 21.0 micrograms/ml hours and 80.6 +/- 21.8 micrograms/ml hours. The two useful drug products (drops and tablets) had similar pharmacokinetic profiles in the dogs and can therefore be regarded as equivalent in this species. PMID- 7886885 TI - Exfoliation syndrome and occludable angles. PMID- 7886890 TI - Isolation of feline respiratory viruses from clinically healthy cats at UK cat shows. PMID- 7886891 TI - Polioencephalomalacia associated with chronic copper poisoning in a Suffolk ram lamb. PMID- 7886892 TI - Meeting clients' needs. PMID- 7886893 TI - Diagnosis of scrapie. PMID- 7886894 TI - Hip dysplasia scheme. PMID- 7886895 TI - Eradication of epidemic pig diseases in the European Union. PMID- 7886896 TI - Evaluation of a modification of the Hudson demand valve in ventilated and spontaneously breathing horses. AB - Hypoxaemia commonly develops during general anaesthesia and in the recovery period in horses. The Hudson demand valve has been used to increase arterial PO2, but it has been found to increase airway resistance considerably when used during spontaneous ventilation. This paper evaluates a modification of the valve designed to reduce this resistance. The effects of the valve and its modification on arterial oxygen (PaO2), and carbon dioxide (PaCO2) tensions were evaluated in four ponies anaesthetised by a total intravenous technique. The valve increased PaO2 from 8.3 +/- 1.1 to 32.7 +/- 7.6 kPa during spontaneous ventilation and to 44.2 +/- 7.4 kPa during intermittent positive pressure ventilation. With the modification, the PaCO2 was increased to 9.0 +/- 2.5 kPa during spontaneous ventilation PaO2 was unchanged by the valve (7.2 +/- 0.4 kPa to 7.1 +/- 0.7 kPa) but it was reduced to 6.4 +/- 0.9 kPa with the modification. The valve was also evaluated in 20 clinical cases during their recovery from halothane anaesthesia. It increased PaO2 from 7.4 +/- 2.1 kPa to 17 +/- 18.3 kPa during spontaneous ventilation and from 8.0 +/- 1.8 kPa to 23.4 +/- 22.2 kPa during positive pressure ventilation. With the modification, PaO2 was increased from 7.8 +/- 1.4 kPa to 10.4 +/- 3.8 kPa during spontaneous ventilation and from 7.6 +/- 1.5 kPa to 14.8 +/- 8.4 kPa during positive pressure ventilation. During spontaneous ventilation PaCO2 was increased from 5.9 +/- 0.4 kPa to 6.2 +/- 0.6 kPa with the unmodified valve and from 6.3 +/- 0.5 kPa to 6.6 +/- 0.5 kPa with the modification.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7886897 TI - Use of midazolam, pethidine, ketamine and thiopentone for the restraint of southern elephant seals (Mirounga leonina). AB - Thirty-two pre-moulting female southern elephant seals (Mirounga leonina) were heavily sedated with midazolam (0.04 mg/kg) combined with pethidine (4 mg/kg). This combination made it possible to give the seals intravenous injections and was rapidly antagonised by naloxone. After sedation with midazolam and pethidine, 2 to 3 mg/kg intravenous thiopentone or ketamine induced light immobilisation for approximately five minutes and allowed the animals to be intubated. Prolonged deep levels of restraint were achieved after sedation with midazolam and pethidine by repeated intravenous doses of approximately 1.5 mg ketamine/kg at 10 minute intervals, to maintain restraint for 60 minutes. PMID- 7886898 TI - Borrelia burgdorferi infections in UK cattle: a possible association with digital dermatitis. PMID- 7886899 TI - Partial ileocaecocolic obstruction due to suspected enterolithiasis in a dog. PMID- 7886900 TI - Efficacy of triclabendazole against Fasciola gigantica in buffaloes in eastern Nepal. PMID- 7886901 TI - Future of the State Veterinary Service. PMID- 7886902 TI - Export of calves. PMID- 7886903 TI - Prevention of rabies. PMID- 7886904 TI - Prevention of rabies. PMID- 7886905 TI - Ostertagiasis in suckler cows. PMID- 7886906 TI - Transmission of Brucella ovis by ewes. PMID- 7886907 TI - Major antigens of Cryptosporidium parvum recognised by serum antibodies from different infected animal species and man. AB - Serum humoral immune response to Cryptosporidium parvum was evaluated in six species: mouse, rabbit, lamb, calf, pig and man. Electrophoretic and immunoblot analysis showed that specific animal antibody response appeared between Day 4 and Day 15 post inoculation. The two main target antigens had apparent molecular weights of 15-17 and 23 kDa. They were recognised by each species studied. Serum IgA intensively recognised the 15-17 kDa antigen, except in rabbit. This study demonstrates that these two antigens are consistent targets of humoral immune response and can therefore be of great interest in studies of therapy/prophylaxis. PMID- 7886908 TI - Ostertagia ostertagi: changes in lymphoid populations in the local lymphoid tissues after primary or secondary infection. AB - The purpose of this study was to begin to define the changes in the local lymphoid tissues that accompany Ostertagia ostertagi infection in naive and immunized calves. Abomasal lymph nodes were taken from calves beginning as early as 2 days post-infection. Phenotypic changes in the resulting lymphocyte populations were assessed by flow cytometry utilizing monoclonal antibodies specific for the cell surface determinates CD2, CD4, and CD8. Changes in antigen specificity were determined by limiting dilution analysis utilizing antigen derived from fourth-stage O. ostertagi. Primary infection of naive calves caused a rapid 30-40% decrease in the percentage of T cells in the abomasal lymph nodes. This decrease in T cell percentage was due to a decrease in cells bearing the CD4 marker, a marker usually associated with helper T cells. Immunized calves were able to maintain normal T cell percentages of 50-60% for the first 5 weeks of infection. Immunization greatly increased the total number of Ostertagia-specific T cells in the abomasal lymph nodes owing to a marked increase in the size of the lymph nodes. Challenge infection of naive and immunized calves caused an increase in the frequency of parasite-specific T cells in both groups, but the increase was more rapid in the previously immunized calves. Within 5 weeks of infection, Ostertagia-specific cells could not be detected in the abomasal lymph nodes. These results indicate that the critical time period for expansion and regulation of Ostertagia-specific T cells in infected calves is early in the infection at a time that coincides with larval development. In addition, previous exposure to parasite antigens appears to result in more rapid responses and in the maintenance of normal ratios of T cell subpopulations in the draining lymphoid tissues. PMID- 7886909 TI - Oviposition and development of face flies in dung from cattle on herbage and supplemented herbage diets. AB - Dung was collected from Angus cattle (Bos taurus L.) fed (ad libitum) hays of endophyte-free (EF) and endophyte (Acremonium coenophialum Morgan-Jones and Gams) infected (EI) tall fescue (Festuca arundinacea Schreb.), smooth bromegrass (Bromus inermis Leyss.), red clover (Trifolium pratense L.), alfalfa (Medicago sativa L.), and alfalfa-smooth bromegrass (1:1 w/w) and green-chopped Kentucky bluegrass (Poa pratensis L.). Samples of dung were subsequently collected from the same animals offered the same herbage diets supplemented each day with ground maize (Zea mays L.) kernels at 0.35 kg per body weight. Dung from both sources were used in bioassays to establish oviposition preferences of face flies (Musca autumnalis De Geer). When offered dung from herbage diets, face flies deposited 38.3% of their eggs on dung derived from EF tall fescue diets, 9.9% on dung from EI tall fescue diets, 21.0% on dung from alfalfa diets, 7.4% on dung from red clover diets and 22.8% on dung from alfalfa-bromegrass diets. Face flies avoided ovipositing in dung from cattle ingesting bromegrass hay and Kentucky bluegrass green-chop. Supplements increased oviposition preference of face flies for dung from cattle ingesting Kentucky bluegrass greenchop to 19.1% at the expense of oviposition on dung from cattle ingesting alfalfa hay diets (4.5%), otherwise, they had little effect on oviposition preference ranking. Growth and development of first instar larvae of face flies was also measured in bioassays of dung from cattle on herbage and supplemented herbage diets. The presence of endophyte reduced pupation in dung from cattle on tall fescue hay diets from 86.3 to 79.8% and from 90.1 to 73.2% in dung from cattle on supplemented tall fescue hay diets. Pupal liveweights averaged 27.5 mg on dung from cattle on EF tall fescue diets, 22.1 mg from dung of cattle on EI tall fescue diets, 22.2 mg from dung of cattle on supplemented EF tall fescue diets and 24.0 mg from dung of cattle on supplemented EI tall fescue diets. Eclosion and the sex ratio of adults were not affected by dung from cattle on different source diets. PMID- 7886910 TI - Natural Cryptosporidium muris infection of the stomach in laboratory mice. AB - Histopathological findings were described in naturally infected laboratory mice in conjunction with the presence of oocysts in the feces related to cryptosporidiosis of the stomach. Diagnosis of infection was made by the observation of oocysts which were indistinguishable from those of Tyzzer's original description of Cryptosporidium muris seen in feces. In addition to this, endogenous developmental stages of the parasite in histologic preparations of tissues obtained at the time of postmortem examination were observed only in the gastric glands of the stomach. In light microscopy, numerous small, spherical to ovoid, basophilic developmental stages of the parasite, embedded in the epithelial microvilli of the stomach, were observed. Most gastric glands were dilated and filled with numerous free or embedded parasites. The gastric glands contained degenerated and atrophied epithelial cells. However, no signs suggested acute inflammation. No lesions or parasites were found in other portions of the gastrointestinal tract or other epithelial tissues of the body. PMID- 7886911 TI - Determination of Toxoplasma gondii in several organs of cattle by carbon immunoassay (CIA) testing. AB - Samples of muscle, heart, liver and lung were tested for the presence of Toxoplasma gondii using mice as a biologic detector and the carbon immunoassay (CIA) for immunological diagnosis. In positive tissues the percentage of samples positive ranged from 10 to 50% which indicates the importance of cattle in the epidemiology of Toxoplasma in Costa Rica. We discuss these findings in relation to the transmission of the parasite in Costa Rica. PMID- 7886912 TI - Enteric coccidia of Cashmere goats in southwestern Montana, USA. AB - A survey of enteric coccidia was made in a Cashmere goat herd in Montana, USA. Eimerian oocysts were found in 97.2% of 616 fecal samples. Newly weaned wethers and does had higher oocyst counts than yearling wethers. Nine Eimeria species were identified, with Eimeria arloingi, Eimeria ninakohlyakimovae and Eimeria alijevi jointly comprising 88.3% of all oocysts recovered. These three species and Eimeria hirci were present in all specimens examined. Prevalence of the other species was as follows: Eimeria caprina, 88.2%; Eimeria jolchijevi, 70.6%; Eimeria christenseni, 32.4%; Eimeria caprovina, 29.4%; Eimeria apsheronica 26.5%. PMID- 7886913 TI - The overwintering of eggs, intramolluscal stages and metacercariae of Fasciola hepatica under the temperatures of a Mediterranean area (Madrid, Spain). AB - The survival of embryonated and unembryonated eggs, of snails with mature or immature infection and of metacercariae over the winter of a Mediterranean area was analyzed. Embryonated eggs were more resistant than unembryonated eggs to cold weather, leaving a residual contamination which was responsible for earlier spring infection of the snail. Overwintering was similar in snail populations with both mature and immature infections although the lifespan was shorter in the former. Both snail populations survived in the mildest winter but not in the coldest. Only metacercariae from mid autumn were able to overwinter in an significant proportion (45%) but they were non-viable by mid spring. Our results suggest that in very cold winters no risk for grazing animals should be expected in spring. PMID- 7886914 TI - Explanatum explanatum (Creplin, 1847) Fukui, 1929, in buffaloes in the Ahwaz area, southwest Iran. AB - Explanatum explanatum (Creplin, 1847) Fukui 1929, was found in three indigenous buffaloes in the west Ahwaz area, southwest Iran for the first time. The presence of this amphistome in bile ducts caused remarkable fibrosis of submucosa ad hyperplasia of the endothelial layer, such that villus-like structures and protuberances were formed in large bile ducts of the infected livers. PMID- 7886915 TI - Fatal toxoplasmosis in five cats. AB - Fatal toxoplasmosis was diagnosed in five of 155 cats necropsied in Denmark during a 2 year period, thus representing 3.2% of the necropsied animals. Lesions were dominated by scattered necrotic foci in liver and spleen. Toxoplasma gondii was demonstrated primarily by an immunoperoxidase technique. The clinical signs were rhinitis, conjunctivitis, dyspnoea and neurological malfunction. The relatively high prevalence indicates that clinical and fatal toxoplasmosis, naturally acquired, seems more frequently occurring among cats than is generally assumed. PMID- 7886916 TI - Resistance to benzimidazole anthelmintics by Haemonchus contortus in goats in peninsular Malaysia. AB - A previous study had suggested that local strains of goat trichostrongyles, comprising largely Haemonchus contortus, might have developed resistance to benzimidazole anthelmintics. A trial involving 18 goats was conducted to confirm this. There was a significant (P < 0.01) reduction in worm burdens in goats given levamisole, but this was not so for those animals given albendazole, fenbendazole, oxfendazole and mebendazole (P > 0.05). PMID- 7886917 TI - Multiple and multigeneric anthelmintic resistance on a sheep farm in Malaysia. AB - The anthelmintic efficacy of benzimidazoles, levamisole, closantel, ivermectin and moxidectin was evaluated on an institutional farm in Malaysia using faecal egg count reduction tests, controlled slaughter trials and an in vitro egg hatch assay. The results of this study indicated simultaneous resistance of Haemonchus contortus against benzimidazoles and ivermectin and of Trichostrongylus colubriformis against benzimidazoles and levaminsole on the same farm. Moxidectin was effective against the ivermectin resistant H. contortus. PMID- 7886918 TI - The outdoor survival of Sarcocystis gigantea sporocysts. AB - Sporocysts of Sarcocystis gigantea in cat faeces were placed in vented polystyrene tubes and superficially buried in both open and shaded sites. Their survival, as measured by their ability to excyst in vitro, was then monitored during the course of two separate experiments extending over 12-month periods. The results showed that the viability of these sporocysts declined most rapidly over the summer months and suggested that they were unlikely to remain infective for more than 1 year. PMID- 7886919 TI - A review on vaccination against protozoa and arthropods of veterinary importance. AB - The recent advances in immunology and biotechnology have stimulated much research on the control of parasitic diseases through vaccination. This is a review of the state of the art regarding important protozoan and arthropod veterinary parasites. A live oocyst vaccine for avian coccidiosis is still in use but much work has been done on the identification, cloning, and assay of protective antigens. The sporozoites of Eimeria tenella have been the preferred subject and at least four recombinant antigens have already been tested with partial success. Premunization against babesiosis is still widely used in Latin America as is a live vaccine with attenuated parasites in Australia. At least three Babesia bovis and three Babesia bigemina antigens that generate partial protection have been produced as recombinant proteins. A vaccine against canine babesiosis is being commercialized in France. Infection-treatment is still used to vaccinate against Theileria parva and a schizont vaccine against Theileria annulata. Recombinant sporozoite antigens have been assayed with partial success against both species but the identification and administration of protective schizont antigens, regarded as the most important, still requires considerable work. The immunological control of African trypanosomoses is still impaired by the antigenic variation that the parasites experience during the infection. Although some possibilities exist, most specialists are pessimistic about the promise of developing a vaccine in the near future. Control of Boophilus ticks with an occult tick intestine recombinant antigen seems to have potential in inhibiting reproduction of the tick but salivary antigens appear to be more effective at inhibiting feeding and pathogen transmission. Vaccination with a Hypoderma protein, recently cloned, has induced 90% protection against subsequent infestations. It is very likely that effective vaccines against veterinary parasites will become available in the near future. PMID- 7886920 TI - A multiple antigen detection dipstick colloidal dye immunoassay for the field diagnosis of trypanosome infections in cattle. AB - Monoclonal antibodies (McAbs) were developed against aspartate aminotransferase purified from Trypanosoma brucei rhodesiense bloodstream form (bf) soluble extracts using a combination of anion-exchange and hydrophobic interaction chromatography. McAb 1A1 was Trypanozoon and Nannomonas specific while 2F1 was Trypanozoon bloodstream form specific. A dipstick colloidal dye immunoassay (DIA) was employed as a field diagnostic test for African trypanosome infections and designed using affinity purified polyclonal antibodies (PcAbs) raised against T. b. rhodesiense bf and the two McAbs, 1A1 and 2F1. PcAbs were adsorbed onto Palanil Red dye particles and used as dye reagents. Dipsticks were dotted with the three different antibodies, which captured trypanosomal antigens in samples tested, while the dye reagent bound to the captured antigens; the presence of coloured dots on the dipstick identified trypanosome infections. A field trial of the DIA was carried out in southeastern Uganda. A total of 1686 cattle from seven areas were bled and tested by DIA and haematocrit centrifuge technique (HCT). A total of 798 cattle (47.3%) were found to be trypanosomal antigen positive by DIA while only 162 (9.6%) were revealed to harbour trypanosomes by HCT, of which 151 (93%) were also positive by DIA. PMID- 7886921 TI - Appetite depression in sheep experimentally infected with Fasciola hepatica L. AB - The purpose of this study was to determine the effects of experimental fasciolosis at various stages of development on the daily food intake of sheep. Five male Churra sheep, 4 months of age, were infected orally with 300 Fasciola hepatica metacercariae over a 30 day period. There was a significant increase in serum glutamate dehydrogenase (GLDH) activity from 40 days post-infection and in aspartate aminotransferase (AST) activity from 60 days post-infection. Both enzyme activities reached maximum levels in the serum of infected animals at 80 days and then progressively decreased. Serum gamma-glutamyltransferase (GGT) activity was significantly increased from 80 to 120 days post-infection. Glycaemia was significantly decreased from 60 days post-infection. The average daily food intake was shown to steadily decrease until approximately 100 days. The coincidence of decreased food intake with the period of significant increase, both in AST and GLDH activities, indicated that damage caused around the time of migration of immature flukes through the liver parenchyma may be involved in appetite depression. PMID- 7886922 TI - Survey in central Kentucky for prevalence of Anoplocephala perfoliata in horses at necropsy in 1992. AB - A total of 118 horses was examined at necropsy in central Kentucky for the tapeworm Anoplocephala perfoliata. The examination period was between 28 August and 21 December 1992. Prevalence was 64% for Thoroughbreds (n = 81 examined) and 54% for non-Thoroughbreds (n = 37 examined). The number of tapeworms per infected horse varied from one to 853. Data on infections are categorized by breed, sex (n = 38 males, 8 geldings, and 72 females), age (1-31 years), and month of necropsy of the horses. PMID- 7886923 TI - Studies on the control of Toxocara canis in breeding kennels. AB - The control of Toxocara canis was investigated in naturally infected unweaned puppies. Anthelmintic treatments were administered to three litters of pups at 2, 4 and 6 weeks of age. When either a new combination anthelmintic containing febantel, pyrantel embonate and praziquantel or fenbendazole was used, the faecal egg output over the first 7 weeks of life was reduced by more than 80% and worm burdens by over 90%. In contrast, piperazine adipate had no appreciable effect on T. canis egg output, even though worm burdens were reduced by 86% by 7 weeks of age. In a further trial using three litters, the worm burden of pups treated with the combination anthelmintic was profiled before and after the 2 week dose and after the 4 week dose. Although worm numbers were substantially reduced by treatment, there was evidence of significant reinfection taking place throughout the control programme. It is concluded that more potent anthelmintics can provide longer term benefits by reducing the numbers of T. canis eggs shed into the environment, but that multiple dosing remains essential for this purpose. PMID- 7886924 TI - Comparison of daily and monthly pyrantel treatment in yearling thoroughbreds and the protective effect of strategic medication of mares on their foals. AB - Studies on a Thoroughbred breeding farm in Ohio were done to: (1) compare the effects of daily administration of pyrantel tartrate feed pellets with monthly administration of a pyrantel pamoate paste to yearling horses (21 January-3 September); (2) assess the effects of daily pyrantel tartrate given strategically in spring/summer to foaling mares (1 April-16 August) and given for a prolonged period to barren mares (21 January-3 September); (3) determine if strategic medication of foaling mares with daily pyrantel tartrate protected their foals until weaning. There were no differences in cyathostome egg counts, pasture larval counts, body condition scores, or body weights of yearlings treated with daily pyrantel tartrate or monthly pyrantel pamoate. Both treatments failed to maintain fecal egg counts of yearlings below 100 eggs per gram (epg), and mean counts exceeded 400 epg (pyrantel pamoate) and 700 epg (pyrantel tartrate) in August and September, resulting in a sharp, but moderate increase in pasture infectivity in October. By contrast, prolonged or strategic use of daily pyrantel tartrate in mature horses were each highly effective in reducing pasture contamination and infectivity with cyathostome eggs and larvae respectively. Strategic medication of foaling mares provided protection of their foals until weaning and first treatment of foals was delayed until after weaning when mean strongyle counts exceeded 100 epg. Treatment of weanlings with pyrantel pamoate had little effect on egg counts. A comparative anthelmintic study with ivermectin, oxibendazole, and pyrantel pamoate confirmed earlier studies showing reduced efficacy of anthelmintics in young horses. PMID- 7886925 TI - Genes coding for Shiga-like toxins in bovine verotoxin-producing Escherichia coli (VTEC) strains belonging to different O:K:H serotypes. AB - Forty-six verotoxin-producing Escherichia coli (VTEC) strains isolated from diarrhoeic and healthy calves in Spain were examined for DNA sequences homologous to genes for verotoxins (VT1 and VT2) and enterotoxins (LT-I, LT-II, STaH, STaP and STb). Hybridisation showed that 26 (57%) of VTEC strains carried VT1 genes, 13 (28%) possessed VT2 genes, and 7 (15%) carried both VT1 and VT2 genes. No VTEC strains hybridised with DNA probes for enterotoxins. A correlation was found between the serotype and type of VT produced. Thus, all strains of serotypes O26:K-:H11 (13 strains), O103:K-:H2 (3 strains) and O128:K?:H- (4 strains) hybridised with the VT1 probe only, whereas all strains of serotypes O4:K-:H4 (3 strains) and O113:K-:H21 (4 strains) were positive with the VT2 probe only. By contrast, O81:K?:H28 (2 strains) and O157:K-:H- (2 strains) strains hybridised with both VT1 and VT2 probes. One strain of serotype O157:K-:H7 was VT2 positive. PMID- 7886926 TI - Immunity in pigeons against homologous and heterologous serotypes of Streptococcus bovis after infection. AB - Groups of 20, 20 and 10 pigeons were intravenously inoculated with 1 x 10(9) CFU of a Streptococcus bovis serotype 1, 2 and 3 strain, respectively. Groups which received the highly virulent serotypes 1 or 2 strains were treated with antibiotics starting from 2 days post inoculation in order to prevent the development of clinical signs. Pigeons inoculated with the low virulence S. bovis serotype 3 strain were left untreated. Another group of 10 non-inoculated pigeons was used as challenge control. Four weeks later, pigeons were challenged intravenously with S. bovis serotype 1. Morbidity after challenge infection was 19%, 36% and 70% in groups previously inoculated with serotypes 1, 2 and 3, respectively, whereas it was 100% in the control group. Results demonstrate that pigeons developed significant protective immunity to S. bovis serotype 1 septicaemia following infection with S. bovis serotype 1 and 2 strains but not after infection with the serotype 3 strain. Protection did not correlate with the presence of antibodies as detected in ELISA. PMID- 7886927 TI - Purification and quantification of Fusobacterium necrophorum leukotoxin by using monoclonal antibodies. AB - Monoclonal antibodies (Mabs) were produced to the leukotoxin of Fusobacterium necrophorum. Two mAbs (F7B10 and E12E9) partially neutralized leukotoxin activity, as determined by a tetrazolium (MTT)-dye reduction assay with bovine polymorphonuclear neutrophils as target cells. Immunoblot analysis showed that both clones reacted with antigens of 110 and 131 kilodaltons. Epitope analysis showed that the two mAbs recognized the same epitope. An affinity column containing immobilized mAb F7B10 was used to purify leukotoxin from crude toxin. Affinity chromatography of 1 ml of culture supernatant resulted in 0.67 microgram or 1350 units of leukotoxin. Leukotoxin was quantitated by a sandwich enzyme linked immunosorbent assay using mAb F7B10 as the capture antibody and as the biotinylated indicator. The minimal detectable level was approximately 1 ng, corresponding to 2 leukotoxin units in the sample. PMID- 7886928 TI - Tuberculosis in imported hyrax (Procavia capensis) caused by an unusual variant belonging to the Mycobacterium tuberculosis complex. AB - Tuberculosis was diagnosed in an adult female hyrax (Procavia capensis) imported from South Africa and held in a captive colony at the Perth Zoo. An organism similar to Mycobacterium microti was isolated from the lung of this animal and the lung of an adult male hyrax in the colony. The organism was not pathogenic to rabbits or guinea pigs. Protein profiles and RFLP patterns using the probes IS6110 and pTBN12 showed both hyrax isolates were identical. These isolates were similar to a M. tuberculosis complex strain isolated from dassies (hyrax) in the late 1950s in South Africa and to M. microti, but appeared to be more closely related to the "dassie bacillus". It is likely that at least one of the hyrax was infected at the time of collection in South Africa. The finding of tuberculosis in these imported animals highlights concern over the lack of suitable tests for the detection of tuberculosis in unusual animal species such as these, and the problems that can arise as a result of the importation of infected animals. PMID- 7886929 TI - Serological and genotypic characterization of group A rotavirus reassortants from diarrheic calves born to dams vaccinated against rotavirus. AB - Two strains of bovine rotavirus (BRV), designated strain Nebraska Scottsbluff-1 (NS-1) and NS-2, were isolated from 2 neighboring cow-calf beef cattle ranches where dams had been vaccinated with a commercial vaccine containing group A BRV strain Neonatal Calf Diarrhea Virus (NCDV)-Lincoln (P1:G6). Northern blot hybridizations using whole genomic RNA probes indicated that strains NS-1 and NS 2 had identical group A RNA electrophoretic patterns and were homologous at all gene segments. Strain NS-1 was compared with reference group A BRV strains using serological and genotypic methods. In vitro virus neutralization assays indicated that strain NS-1 was neutralized by a G6-specific neutralizing monoclonal antibody (mAb) and guinea pig hyperimmune serum (GPHS) raised against BRV strain B641 (P5:G6), but not by G10-specific neutralizing mAb or GPHS raised against BRV strain B223 (P11:G10). Nucleic acid hybridization experiments using whole-genomic RNA probes revealed that gene segment 4 of strain NS-1 differed from BRV strains NCDV-Lincoln and B223, but hybridized with strain B641. Conversely, gene segment 5 of strain NS-1 hybridized with BRV strain B223, but not with BRV strains NCDV Lincoln and B641. A G-specific cDNA probe produced by reverse transcription polymerase chain reaction (RT-PCR) amplification of strain NS-1 hybridized specifically only with G6 strains NCDV-Lincoln and B641, but not with G10 strain B223. Co-electrophoresis experiments using strains NS-1, B641, and B223 further confirmed these results, suggesting that strain NS-1 was a naturally-occurring reassortant BRV between strains B641 and B223. Taken together these results indicated that a naturally-occurring group A BRV reassortant with a P gene different from the vaccine virus was responsible for the diarrheal syndrome observed on both ranches. Results from this study also indicate the existence of at least 2 different gene segments 5 among group A BRV infecting cattle. PMID- 7886930 TI - Systemic vaccination with inactivated bovine virus diarrhoea virus protects against respiratory challenge. AB - Inactivated bovine virus diarrhoea virus, strain 11249nc, inoculated subcutaneously three times with Quil-A into calves protected against intranasal challenge with the same strain. Virus was isolated from nasopharyngeal swabs taken 4 to 8 days post challenge and blood taken 4 to 6 days post challenge from control calves but not from vaccinated calves. A second strain of virus, Ky1203nc, was selected on the basis of previously established data on its antigenicity and the amount of viral antigen produced by five cell cultures compared using an ELISA. Cultures of one cell line, MDBK, yielded a greater amount of viral antigen than the others. Strain Ky1203nc grown in MDBK cells was inactivated with beta-propiolactone, mixed with adjuvant and used as a vaccine inoculated into calves subcutaneously three times. All of 5 calves were protected against intranasal challenge with a heterologous strain. In contrast virus was isolated from nasopharyngeal swabs taken from 5 control calves and from the blood of 4 controls. All 5 control calves, but none of the vaccinates, had a leukopenia after challenge. We conclude that the selected strain and system of vaccine preparation provide an effective means of protecting calves against respiratory infection and that live vaccines are not required to protect against challenge via the respiratory tract. PMID- 7886931 TI - Bovine immunodeficiency virus: incidence of infection in Mississippi dairy cattle. AB - Bovine immunodeficiency virus (BIV), a lentivirus, was originally derived from a Holstein cow with persistent lymphocytosis and severe wasting. The virus is known to occur sporadically throughout the United States and perhaps across the globe, but epidemiological data concerning the incidence of BIV are meager and the virus was previously unreported in Mississippi animals. This study examined the seroepidemiology of BIV infection from two Mississippi dairy herds (Coastal Plains and MSU). Serology revealed a 38% incidence of BIV infection in Coastal Plains animals and a 58% incidence in MSU animals. A cumulative BIV seroprevalence of 50% was found in the Mississippi animals, and BIV seroprevalence increased with increasing age of the animals. Peripheral blood leukocytes of age matched BIV seropositive and seronegative animals were enumerated to assess any effect of BIV infection on leukocyte populations. No significant differences were found in total leukocyte populations or leukocyte subpopulations between BIV seropositive or seronegative animals. These data indicate that BIV infection is prevalent in Mississippi animals, but the role of BIV in bovine disease remains unclear. PMID- 7886932 TI - Bovine leukaemia virus: rapid detection of proviral DNA by nested PCR in blood and organs of experimentally infected calves. AB - The early stage of bovine leukaemia virus (BLV) infection was studied in experimentally infected calves in order to assess the diagnostic applicability of a double polymerase chain reaction (PCR). In addition, the kinetics of infection and virus distribution were evaluated. To simulate the natural route of virus transmission, the calves were infected by transferring two different infectious doses of whole blood from a BLV infected cow. The establishment of infection was determined by the double PCR and syncytia formation assay and by indirect serological methods including indirect ELISA, gp51/p24 ELISA, agar gel immunodiffusion (AGID) and Western blotting. BLV antibodies were first detected in ELISA on post infection (p.i.) day 26. Close agreement was found between the results of the various indirect methods. BLV infection was first detected in peripheral blood lymphocytes (PBL) by the PCR on p.i. day 7. No animal became seropositive to BLV prior to direct detection of BLV infection by the PCR. At slaughter, urine and saliva specimens as well as various organs were collected from the calves and tested by the double PCR. Several of the organs yielded positive results: e.g. spleen, uterus, liver, kidney, abomasum, and lymph nodes. Nine out of eleven spleen suspensions were positive by the PCR, including the spleen from one calf, which otherwise remained negative in all tests throughout the experiment. This phenomenon indicates that an animal may be infected without detectable levels of BLV proviral DNA in PBLs and without circulating antibodies, further emphasizing the diagnostic importance of the PCR. The findings indicate that the PCR is the most rapid method for the early detection of BLV infection in cattle and a valuable tool for studying the tropism of the virus. PMID- 7886933 TI - Vaccination of pigs with replication-defective adenovirus vectored vaccines: the example of pseudorabies. AB - The efficacy of a recombinant human adenovirus type 5 expressing gD, one of the immunogenic glycoprotein of pseudorabies virus, was tested in pigs. Due to the deletion of the E1a gene, the recombinant virus is unable to replicate in non transcomplementing cells but is capable of eliciting an immune response against gp50 after inoculation into animals. The virus was formulated in a water/oil/water emulsion, a strategy previously shown to enhance the immune response against the virus-induced gp50. Pigs of 18-25 kg were vaccinated twice and the recombinant virus was not isolated from nasal and rectal swabs taken after each injection of the vaccine. High levels of neutralizing antibodies were induced by the vaccination. Protection against a severe challenge was effective, as measured by growth performance (dG = 1.73), and reduction of the time of excretion of the challenge strain (mean time: 4.4 days for the vaccinated and 7.9 days for the control pigs). These results show that non replicating adenoviruses are able to induce a strong protective immune response against foreign genes in pigs, which may be of general interest for the design of pig vaccines. PMID- 7886935 TI - Detection of verotoxigenic Escherichia coli in bull semen using the polymerase chain reaction. AB - Oligonucleotide primers used in a polymerase chain reaction (PCR) protocol detected the verotoxin 2 (VT2) gene in E. coli present in experimentally contaminated bull semen. The VT2 (Shiga-like toxin II [SLT-II]) primers targeted a 346-bp fragment of the gene coding for the A subunit of the toxin. PCR products, corresponding to the VT2 gene sequence, were amplified from template E. coli nucleic acid extracted from 18-h broth culture and from E. coli in contaminated semen in the undiluted state, diluted in egg yolk-Tris and diluted in milk. The sensitivity of the assay to detect E. coli was determined to be 1 pg of nucleic acid, and as few as 10-20 E. coli organisms/ml could be detected in raw and diluted semen. Preliminary confirmation of the PCR product was accomplished by slot blot hybridization to a radiolabeled specific oligoprobe. Sequencing of the PCR products identifying VT2 gene sequence revealed 99.7% homology with published gene sequences for VT2. This study demonstrates the feasibility of applying PCR technology for the detection of E. coli in bovine semen. This technique may find wide application for the detection of other pathogens that may be present in semen. PMID- 7886934 TI - An enzyme-linked immunosorbent assay for the detection of marine caliciviruses. AB - An indirect, sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of antigens of vesicular exanthema, San Miguel sea lion viruses and other marine caliciviruses is described. The assay which uses rabbit and guinea-pig antisera to purified antigens of each calicivirus serotype has high sensitivity and is almost totally type-specific. PMID- 7886936 TI - Studies on the survival of canine coronavirus under different environmental conditions. AB - Canine coronavirus (CCV) is a common faecal agent which is difficult to isolate. This study shows CCV to survive well at temperatures below -20 degrees C but not at temperatures above 4 degrees C. The presence of faecal material markedly reduced CCV survival times at temperatures ranging from 20 degrees C to -70 degrees C. Thus, it is suggested that diagnostic faecal material should be diluted 1:10 (w/v) with growth medium and examined at the earliest opportunity. PMID- 7886938 TI - Cucumber mosaic virus 3a protein potentiates cell-to-cell trafficking of CMV RNA in tobacco plants. AB - Contrary to a previous report, electron microscopic studies on the Fny strain of cucumber mosaic virus (CMV)-infected tobacco tissues revealed that plasmodesmata were not structurally modified during CMV infection, nor were virions ever observed in plasmodesmata connecting infected cells. To further explore the basis of CMV infection, experiments were performed on the CMV 3a ORF. The 3a protein of CMV was expressed in and purified from Escherichia coli. The purified protein was labeled with fluorescein isothiocyanate (FITC) and subsequently microinjected into mesophyll cells of mature leaves of Nicotiana tabacum cv. Turkish Samsun NN. Within a brief period (as little as 1 sec), the microinjected FITC-labeled CMV 3a protein moved into neighboring cells. Co-injection of unlabeled CMV 3a protein with 9.4-kDa fluorescein-conjugated dextran (F-dextran) resulted in extensive cell-to-cell movement (diffusion) of the F-dextran, indicating that the 3a protein can interact with and dilate plasmodesmata. Furthermore, co-injection of unlabeled 3a protein with fluorescently labeled infectious CMV RNA molecules resulted in rapid and extensive cell-to-cell transport. In contrast, a mutant form of the 3a protein was unable to traffic from cell to cell, to increase the size exclusion limit of plasmodesmata, or to potentiate cell-to-cell trafficking of CMV RNA molecules. Microinjection studies performed on transgenic tobacco plants expressing the CMV 3a protein indicated that fluorescently labeled CMV RNA moved out of the target cell into the surrounding mesophyll tissue. In addition, expression of the CMV 3a protein also potentiated the cell-to-cell movement of 9.4-kDa F-dextran. Collectively, these results provide direct experimental evidence that the CMV 3a protein functions as the movement protein of CMV. These findings are consistent with the hypothesis that CMV moves from cell-to-cell in the form of a ribonucleoprotein complex. PMID- 7886937 TI - Evaluation of a saline boiled extract, capsular polysaccharides and long-chain lipopolysaccharides of Actinobacillus pleuropneumoniae serotype 1 as antigens for the serodiagnosis of swine pleuropneumonia. AB - A saline boiled extract (SBE), capsular polysaccharides (CPS) and long-chain lipopolysaccharides (LC-LPS) of Actinobacillus pleuropneumoniae serotype 1 have been evaluated in ELISA for the serodiagnosis of swine pleuropneumonia caused by this serotype. Mean optical densities (ODs) obtained with the three antigens using sera from negative herds as well as from animals experimentally and naturally exposed to A. pleuropneumoniae serotypes 1, 9 or 11 were not significantly different. The positive ELISA reaction with anti-serotypes 9 and 11 was unexpected with the CPS, which are supposed to be serotype-specific; LPS, and to a lesser extent proteins, were present in the CPS and appeared to be responsible for this reaction. In addition, sera from animals exposed to a field strain of A. pleuropneumoniae serotype 3 and to Actinobacillus suis presented a significantly lower mean OD (P < 0.001) when LC-LPS were used. Cross-reacting antigens consisted mainly of LPS core-lipid A present in the SBE and CPS. The specificity and the sensitivity of the ELISA were evaluated using three different cut-off values (the OD plus two, three and four times the standard deviation or SD) obtained with 667 negative sera. The diagnostic sensitivity was of 81% with the three antigens and the different thresholds. The diagnostic specificity was of 84, 86 and 88% for the mean plus two, three and four times the SD respectively using the SBE and the CPS, while that obtained with the LC-LPS was of 96, 98 and 99% using the same thresholds. In conclusion, LC-LPS make an easily obtainable antigen and seem to retain the best specificity while minimizing losses of sensitivity. PMID- 7886939 TI - Sequence of subterranean clover stunt virus DNA: affinities with the geminiviruses. AB - The nucleotide sequences of seven circular, single-stranded DNA components of one isolate of subterranean clover stunt virus (SCSV) have been determined. Each component, of about 1 kb, appears to encode a single open reading frame in the same sense as the encapsidated DNA. Notably, the proteins encoded by two SCSV components are related. Each has a consensus nucleotide binding motif and shares about 40% amino acid identity with the other and with the putative replication proteins of banana bunchy top virus and coconut foliar decay virus. The noncoding regions of the five other SCSV components share a highly conserved noncoding sequence of about 160 nucleotides. All seven components were found to contain a sequence capable of forming a stable stem-loop structure in the noncoding region which contains a conserved 9-nucleotide sequence in the loop, very similar to that of the geminiviruses. In addition, the putative replication proteins of SCSV are similar to those of the geminiviruses. We suggest that the SCSV-like viruses and the geminiviruses share a common ancestor and that this ancestor was more like SCSV in particle structure and genome organisation. PMID- 7886940 TI - The v-Rel oncoprotein complexes with new Rel- and RelA-related proteins in transformed cells. AB - The v-Rel oncoprotein of the Rev-T retrovirus interacts with a number of cellular proteins in transformed chicken spleen cells including p40/I kappa B alpha, p68c Rel, hsc70, and the p124 and p115 precursors for the p50 and p52 subunits of NF kappa B. Here we report that v-Rel associates with at least three other cellular proteins of 75-85 kDa in these cells, as well as with a protein related to human RelA. Western blot analysis of v-Rel immune complexes showed cross-reactivity between all of these factors and antibodies raised against Rel sequences, but none appeared to represent isoforms of c-Rel. Synchronization experiments revealed that the expression and/or association of these proteins with v-Rel varied throughout the cell cycle. Combined with the previously described interaction of v-Rel with known members of the Rel family, these studies strengthen the hypothesis that the interaction of v-Rel with multiple Rel-related proteins may be important for the transformation of lymphoid cells. PMID- 7886941 TI - TCl4.7: a novel lepidopteran transposon found in Cydia pomonella granulosis virus. AB - After the co-infection of larvae of the lepidopteran Cryptophlebia leucotreta with the two baculoviruses C. leucotreta granulosis virus and Cydia pomonella granulosis virus (CIGV and CpGV, respectively), three CpGV mutants and one CIGV mutant carrying insertions of 0.9 to 4.7 kb have been isolated. By cloning, sequencing, and hybridization analysis, one of these insertions was identified as a transposon-like element derived from the C. leucotreta genome. This element, called TCl4.7, was found in the genome of CpGV which naturally replicates in C. pomonella. Sequence analysis suggested that TCl4.7 is 4726 bp in size, flanked by imperfect inverted terminal repeats of 29 bp, and integrated into the target dinucleotide TA. TCl4.7 encompasses an open reading frame sharing homologies to transposase genes of the Tc1-related transposable elements found in Caenorhabditis and in Drosophila species. The open reading frame might represent a pseudogene since it is missing an ATG start codon. The integration site of TCl4.7 is located in a non-protein-coding region of the CpGV genome at m.u. 9.5. In bioassays the TCl4.7-carrying virus and all the other mutants except for one showed LC50 values similar to those of CpGV and CIGV. This is the first report of the horizontal escape of a transposable element during the in vivo infection of lepidopteran larvae by granulosis viruses. PMID- 7886942 TI - Characterization and localization of the equine herpesvirus 1 major DNA binding protein. AB - In previous studies of equine herpesvirus 1 (EHV-1) gene regulation, we observed an abundant early infected cell polypeptide (ICP), designated ICP130, which appeared in reduced amounts in cells infected with defective interfering particle rich EHV-1 stocks compared to standard EHV-1-infected cells. To characterize this ICP further, a monoclonal antibody (MAb) was developed to EHV-1 ICP130 and used to (1) affinity purify ICP130, (2) examine ICP130's ability to bind DNA, and (3) define the synthesis and intracellular localization of ICP130 during productive EHV-1 infections. Although anti-ICP130 MAbs did not crossreact with any HSV-1 protein in immunoblots, a polyclonal antiserum against HSV-2 major DNA binding protein (ICSP11,12) did react with purified EHV-1 ICP130. DNA band shift assays indicated that (1) the mobility of shifted bands representing DNA/EHV-1-infected cell protein complexes was further decreased by the addition of either anti ICP130 MAbs or anti-ICSP11,12, but not by the addition of irrelevant MAbs, (2) the ability of ICP130 to complex with DNA was not sequence dependent, (3) ICP130 associated with both single- and double-stranded oligomers, and (4) similar supershifted patterns were produced using affinity-purified ICP130 and anti ICP130 MAbs. During productive infection, ICP130 initially localized rapidly and exclusively to the infected cell's nucleus in a generalized, fine granular pattern. Over the course of infection, this pattern typically progressed to include several large, intensely reactive intranuclear granules, and by 6 hr p.i. some cytoplasmic reactivity also was visible. In < 5% of the cells, a dense, fibrillar network surrounding the nucleus was observed instead. The progressive changes in nuclear localization depended upon the onset of viral DNA replication, and once the late pattern was established, ongoing DNA synthesis was required to maintain it. The results indicate that ICP130 is the previously reported EHV-1 counterpart of the HSV major DNA-binding protein and is similar, but not identical, in many aspects. PMID- 7886943 TI - Replication of transfected plasmid DNA by cells infected with African swine fever virus. AB - Recombinant plasmids containing African swine fever virus (ASFV) DNA fragments covering all the virus genome were transfected into infected cells in order to detect viral origins of DNA replication. Plasmid replication was monitored by sensitivity to MboI, which cleaves only replicated, unmethylated DNA, and resistance to DpnI, which cleaves only the same methylated sequence. All the recombinants replicated to a similar extent, indicating that ASFV does not use a preferred origin for DNA replication. Circular plasmids without viral inserts were also replicated, but linearized plasmids or lambda bacteriophage DNA were not replicated. Replicated plasmid DNA began to accumulate with a time course similar to viral DNA, starting between 6 and 12 hr p.i. and increasing steadily for about 18 hr. This apparent dependence on viral functions was confirmed by the sensitivity of plasmid replication to phosphonoacetic acid and resistance to aphidicolin and by the reduction of replication in cells infected with a mutant defective in DNA replication. Replicated plasmid DNA present as unit length circles and as large dimension forms, probably head-to-tail concatemers. The results of two-dimensional electrophoresis (neutral/alkaline) favor a rolling circle mechanism for plasmid DNA replication. PMID- 7886944 TI - In vitro transcription of the double-stranded RNA bacteriophage phi 6 is influenced by purine NTPs and calcium. AB - The double-stranded RNA bacteriophage phi 6 contains a virion-associated RNA dependent RNA polymerase complex. Removal of the virus envelope and the nucleocapsid surface protein, P8, reveals a nucleocapsid core particle (proteins P1, P2, P4, P7) which is the viral polymerase complex, capable of synthesizing RNA strands of positive polarity. The in vitro plus strand synthesis (transcription) reaction of the particle obtained from the mature virion was optimized and its activation and inactivation were investigated. Purine nucleoside triphosphates (NTPs), binding to a low-affinity binding site in the polymerase complex, activated plus strand synthesis. GTP was the preferred NTP, but dGTP, ddGTP, and the noncleavable analog GMP-PCP could also switch on transcription. This NTP-binding site is probably different from that of the unspecific viral NTPase found in protein P4 and also from that of the rNTP specific RNA polymerase active site. Binding of purine NTPs was sufficient for the switch-on; hydrolysis of the NTP was not required. Besides nucleotides, divalent cations had an effect on phi 6 in vitro plus strand synthesis. Magnesium ions are required for the activity but calcium ions inhibit the reaction. Manganese ions are shown to dissipate the effect of magnesium and calcium ions, leading to uncontrolled, exceptionally high level plus strand synthesis. PMID- 7886945 TI - The 140-kDa RR1 protein from both HSV-1 and HSV-2 contains an intrinsic protein kinase activity capable of autophosphorylation but it is transphosphorylation defective. AB - The 140-kDa RR1 protein from both herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) functions as the large subunit of viral ribonucleotide reductase (RR) and contains an intrinsic serine/threonine protein kinase (PK) activity at the unique NH2-terminal domain. This PK activity is capable of autophosphorylation and reported to transphosphorylate histone and calmodulin by some groups but not by others. It has been suggested that the lack of consensus in the finding of transphosphorylation activity with RR1 protein may be due to HSV strain variations used in different laboratories. In the present study, we have attempted to resolve this issue by immunospecifically isolating the 140-kDa RR1 protein from four different strains of HSV-1 including F, KOS, HF, and MP and three different strains of HSV-2 including G, 333, and MS and subjecting them to immunocomplex kinase assays. In PK assays autophosphorylation of 140-kDa RR1 was readily observed in protein immunopurified from all HSV-1 and HSV-2 strains used in this study. However, using the same assay no transphosphorylation activity was observed with either the 38-kDa RR2 protein present in immunocomplex along with the RR1, or with histone, when added as an exogenous PK substrate. This conclusion is further supported by the evidence that a commercial preparation of PK (protein kinase catalytic subunit from bovine heart) readily phosphorylated histone under the conditions used for RR1 immunocomplex kinase assay. These results show that the 140-kDa RR1 protein contains an autokinase activity but it is incapable of transphosphorylating heterologous substrates such as histone. In addition, we show that the RR enzyme complex (140 and 38-kDa proteins) is associated with purified HSV-2 virions. PMID- 7886946 TI - Identification of essential trans-acting regions required for DNA replication of the Orgyia pseudotsugata multinucleocapsid nuclear polyhedrosis virus: lef-1 is an essential replication gene. AB - A transient replication assay for the identification of baculovirus genes that are essential for replication of an origin-containing reporter plasmid was established for the Orgyia pseudotsugata multinucleocapsid nuclear polyhedrosis virus (OpMNPV). Using a replication origin located on the OpMNPV HindIII-N fragment, we identified a subset of cosmids and plasmids from an OpMNPV cosmid library that was able to supply all the essential trans-acting factors and support replication of the origin-containing plasmid in uninfected Lymantria dispar cells. However, this limited set of DNA's was unable to support replication of a second origin-containing plasmid derived from a different region of the OpMNPV genome. Replication analysis of deletion clones of the HindIII-N fragment led to the identification of a gene, late expression factor 1 (lef-1), that is essential for the transactivation of DNA replication in this system. Transcriptional analysis of lef-1 mapped both early and late transcripts of about 1.75 kb. A motif characteristic of nucleoside triphosphate-binding sites present in the carboxy-terminal region of AcMNPV Lef-1 is not conserved in OpMNPV Lef-1. PMID- 7886947 TI - Delineation of the essential function of bovine herpesvirus 1 gD: an indication for the modulatory role of gD in virus entry. AB - The entry process of alphaherpesviruses consists of two steps, initial virus attachment and subsequent virus penetration involving membrane fusion. Glycoprotein D (gD) of the alphaherpesvirus bovine herpesvirus 1 (BHV 1) is an essential envelope protein, and it has been previously documented that gD plays a significant part in both of the virus entry steps. In order to gain further insight into the virus entry process, we attempted to define the essential function of BHV 1 gD. We replaced the gD transmembrane and cytoplasmic domains with a lipid-addition signal sequence from human decay accelerating factor and produced a stably transfected Madin Darby bovine kidney (MDBK) cell line that expresses a nonfusogenic, glycosylphosphatidylinositol (GPI)-anchored gD. We found that this cell line was able to support the growth of a gD gene-deletion mutant; the resultant gD mutant progeny contained the GPI-anchored gD on its virions and was able to enter into and produce a production infection in MDBK cells. This result suggests that fusion activity does not constitute the essential function of gD. In addition, we found that a gD-null virus (a virus containing no gD on its virion) could infect gD-expressing cells, but not normal MDBK cells. The ability of the gD-null virus to infect gD-expressing cells was dependent on the gD present on the cell surface, since either treating cells with phosphatidylinositol-specific phospholipase C to remove the GPI-anchored gD or incubating cells with gD monoclonal antibodies could block gD-null virus infection. This demonstrates that gD present on the cell surface can act in trans to facilitate the entry of virion lacking gD. This indicates that essential gD function can take place in the absence of gD-mediated virus attachment and membrane fusion. We also found that the gD monoclonal antibodies that block gD null virus entry into gD-expressing cells are strictly restricted to the monoclonal antibodies that show postadsorption neutralization activity, indicating that the trans-acting function exhibited by the gD present on the cell surface represents the same function as defined by postadsorption antibody neurtralization. The results from this study suggest that the essential function of gD in virus entry is to modulate other virus-cell interaction(s) involved in productive virus penetration. PMID- 7886948 TI - Prevalence and geographic genetic variation of hantaviruses of New World harvest mice (Reithrodontomys): identification of a divergent genotype from a Costa Rican Reithrodontomys mexicanus. AB - We recently described a novel hantavirus (HMV-1) of the western harvest mouse Reithrodontomys megalotis. Screening of 181 additional specimens of Reithrodontomys from the United States and Mexico, including samples of R. mexicanus, R. sumichrasti, and R. gracilis of Costa Rica, for antibodies to hantavirus nucleocapsid protein revealed a widespread enzootic of hantavirus infection. Genetic analyses of 7 S genomes of Reithrodontomys-associated hantaviruses demonstrated that the enzootic of HMV-1 extends from central Mexico into the southwestern United States. A presumed deer mouse hantavirus was found in an R. megalotis animal in Mexico. A highly divergent HMV-1-like virus, tentatively called HMV-2, was identified in a Costa Rican R. mexicanus. These data suggest a longstanding radiation of hantaviruses among New World harvest mice. We identify possible opportunities for genetic exchange among hantaviruses of related rodent hosts. PMID- 7886949 TI - Serine/threonine protein phosphatase is required for tobacco mosaic virus mediated programmed cell death. AB - A major gap in our understanding of host response to virus infection is how the molecular signals are passed within infected cells. Tobacco mosaic virus-mediated programmed cell death in genotype NN tobaccos was used to evaluate the hypothesis that these molecular signals are transduced via reversible-protein phosphorylation. Nicotiana tabacum L. (genotype NN) confers a hypersensitive response at the site of virus infection when incubated at a permissive temperature. Activation of serine/threonine protein phosphatase correlated with the temperature-dependent induction of the death program. The serine/threonine protein phosphatase inhibitor okadaic acid inhibited the onset and extent of the hypersensitive response in vivo. Biochemical analysis indicates that protein phosphatase type 1 is activated early in the death program. This is the first indication that serine/threonine protein phosphatase is required in an early event of the host response to virus infection. PMID- 7886950 TI - Replicase-mediated resistance to alfalfa mosaic virus. AB - Tobacco plants transformed with the P1 and P2 replicase genes of alfalfa mosaic virus (AIMV) have been shown to produce functional replicase proteins, permitting their infection with AIMV inocula lacking the genome segments encoding P1 and P2, respectively. To see whether expression of a mutant P2 protein would interfere with the assembly of a functional replicase complex, tobacco plants were transformed with modified P2 genes. When plants were transformed with a P2 gene encoding an N-terminally truncated protein which mimicked the tobacco mosaic virus 54K protein, no resistance was observed with 10 independent lines of transformants. Similarly, when the GDD motif in the full-length P2 protein was changed into VDD, no resistance was observed in 14 transgenic lines. However, when the GDD motif was changed into GGD (5 lines), GVD (15 lines), or DDD (13 lines), 20 to 30% of the transgenic lines showed a high level of resistance to AIMV infection. This resistance was effective to inoculum concentrations of 10 to 25 micrograms/ml of virus and 100 micrograms/ml of viral RNA, causing severe necrosis of control plants. For all transgenic lines, the expression of the transgenes was analyzed at the RNA level. With the GGD, GVD, and DDD mutants, resistance was generally observed in plants with a relatively high expression level. This indicates that the resistance is due to the mutant replicase rather than to an RNA-mediated cosuppression phenomenon. PMID- 7886952 TI - In vitro assembly of cowpea chlorotic mottle virus from coat protein expressed in Escherichia coli and in vitro-transcribed viral cDNA. AB - The small spherical plant virus, cowpea chlorotic mottle virus (CCMV), provides an ideal system to examine spherical virus assembly. We have modified the CCMV in vitro assembly system to produce virions from coat protein expressed in Escherichia coli and viral RNA transcribed in vitro from full-length cDNAs. Examination of the in vitro-assembled particles with cryoelectron microscopy and image reconstruction techniques demonstrates that the particles are indistinguishable from plant purified particles at 2.5 nm resolution. Mutational analysis of the coat protein N- and C-terminal extensions demonstrate their respective roles in virus assembly. The N-terminus is required for assembly of RNA containing particles but not for the assembly of empty virions. The C terminus is essential for coat protein dimer formation and particle assembly. PMID- 7886951 TI - A side chain at position 48 of the human immunodeficiency virus type-1 protease flap provides an additional specificity determinant. AB - Substitution of glycine with glutamic acid at position 48 of the human immunodeficiency virus protease resulted in an enzyme with reduced activity on one of the protease processing sites in the viral Pol polyprotein precursor. Cleavage at this site was restored by a second-site substitution in the substrate replacing an aspartic acid with either glycine or asparagine. These results suggest that the glutamic acid side chain in the mutant protease has an unfavorable charge-charge interaction with this position in the substrate. Cleavage of a processing site in the viral Gag polyprotein precursor with the mutant enzyme was enhanced, and this enhancement was dependent on the presence of an arginine residue in the substrate, again suggesting a charge-charge interaction. The potential for such interactions was confirmed using molecular modeling. The effect of the position 48 substitution was attributed to a 10-fold increase in Km for the processing site in Pol. These results indicate that the addition of a side chain at position 48 can alter the specificity of the HIV-1 protease to substrate in a sequence specific manner and that compensatory changes can be made in the substrate. PMID- 7886953 TI - Chimeric macaque/human Fab molecules neutralize simian immunodeficiency virus. AB - A collection of simian immunodeficiency virus (SIV) neutralizing recombinant Fab fragments was generated using the combinatorial antibody library approach. Functional antibody fragments efficiently expressed in Escherichia coli were identified only in the form of chimeric macaque heavy chain gamma 1 and human light chain kappa. The gamma 1 and kappa chains were derived from a clinically healthy long-term surviving SIVsm-infected cynomolgus macaque and from an asymptomatic HIV-2 seropositive individual, respectively. The combinatorial library was constructed on the surface of filamentous phage using the pComb3 phagemid vector and screened against purified SIVsm surface glycoprotein (gp148). Twelve chimeric clones reacting with the antigen were isolated. Six of these clones showed a pronounced neutralizing activity against SIVsm with effects at concentrations of 0.01-0.1 micrograms/ml. All neutralizing Fab fragments were clonally unrelated as demonstrated by nucleic acid sequencing. These potent neutralizing reagents will be used for prophylactic and therapeutic immune intervention of lentivirus infection in macaques and to map neutralizing determinants of SIV. PMID- 7886954 TI - Foot-and-mouth disease virus undergoes restricted replication in macrophage cell cultures following Fc receptor-mediated adsorption. AB - We have previously reported that foot-and-mouth disease virus (FMDV) can enter an Fc receptor (FcR)-expressing cell line by antibody-dependent enhancement. Since FMDV can establish a persistent infection in animals in the presence of high levels of neutralizing antibodies (carrier state), we examined macrophages for their ability to be infected by the virus in the presence of antibody. The murine macrophage cell line P388D1 or porcine macrophage-monocytes isolated from peripheral blood were incubated with antibody-complexed virus. Under these conditions, host protein synthesis was rapidly inhibited in both cell types, but not in cells incubated either with virus alone or with imine-inactivated antibody complexed virus. Virus-specific structural and nonstructural proteins were synthesized in antibody-complexed virus-infected P388D1 cells, while only nonstructural proteins were detected in porcine macrophage cultures. Negative strand RNAs were detected in both cell types, indicating that RNA replication had taken place. Cultures of P388D1 cells transfected with viral RNA produced very low levels of infectious virus, and infection with virus-antibody complexes, followed by a brief wash with pH 6.0 buffer to remove residual input virus, allowed the detection of low levels of productive replication. Thus, macrophages can be infected with FMDV via FcR-mediated adsorption, and infection of these cells could contribute to pathology or provide a reservoir of infectious virus in carrier animals. PMID- 7886955 TI - Generation of defective interfering RNA dimers of cymbidium ringspot tombusvirus. AB - Inoculation of Nicotiana clevelandii and N. benthamiana plants with in vitro transcripts of both genomic and defective interfering (DI) RNAs of cymbidium ringspot tombusvirus resulted in a rapid accumulation of new DI-like RNA species which were demonstrated by cloning and sequencing to be head-to-tail dimers of unit length DI RNAs. The junction regions of dimers were represented by sequences derived precisely from the 5' and 3' termini of DI RNAs. Only infection with DI RNAs of smaller size (DI-2 and DI-3, 402 and 482 nt, respectively) produced detectable amount of dimers; in contrast, infection with the largest DI RNA (DI 13, 679 nt) was unable to accumulate dimers during viral infection. Analysis of mutant DI RNAs containing deletions or insertions revealed that the size of the monomer molecule is a major factor in the accumulation of dimers. Monomeric DI RNAs were formed in both plants and protoplasts inoculated with in vitro transcribed dimers. No heterodimers were found in plants inoculated simultaneously with DI-2 and DI-3 RNA molecules, which may indicate that replicase is not released from the template during synthesis of dimer molecules. However, the occurrence of a recombinant DI RNA dimer molecule derived from the two DI RNAs suggests that simultaneous infection of the same cells with two DI RNAs did indeed take place and that absence of heterodimers did not depend on compartmentalization. PMID- 7886956 TI - Progression to AIDS in macaques is associated with changes in the replication, tropism, and cytopathic properties of the simian immunodeficiency virus variant population. AB - Human immunodeficiency virus type 1 (HIV-1) typically evolves from a macrophage tropic, noncytopathic virus at early asymptomatic stages of infection to a T-cell tropic, cytopathic, and syncytia-inducing virus population as humans progress to AIDS. This suggests that changes in virus phenotype may influence disease. Because simian immunodeficiency virus (SIV) infection in macaques is a common model system for HIV-1 pathogenesis, we determined whether SIV infection in macaques that develop simian AIDS is associated with a similar shift in viral tropism, replication, and cytopathic properties. The virus that infected the monkeys (SIVMneCL8) and predominated at early times in infection is a macrophage tropic virus that replicates with relatively low efficiency in human T cell lines. The variant populations that arise in macaques as they progress to AIDS are more infectious for human T cell lines, exhibiting enhanced replication in CEM x 174 cells and an expanded host range that includes Molt-4 Clone 8 cells. Infections starting with equal doses of the viruses demonstrated that the late variants are cytopathic and syncytia-inducing compared to SIVMneCL8, but the variants replicate less efficiently in primary macaque macrophages. V3 sequences were generally conserved between the early and the late variants, suggesting that changes in SIVMne tropism, replication, and cytopathicity were apparently not due to alterations in V3. This study demonstrates important similarities in the phenotypic viral changes that accompany development of AIDS in SIV and HIV-1 infections and suggest that SIV may provide a model system for determining whether the rapidly replicating, T-cell-tropic cytopathic variants present late in infection and disease are indeed important in determining progression to AIDS. PMID- 7886957 TI - Analysis of simian hemorrhagic fever virus (SHFV) subgenomic RNAs, junction sequences, and 5' leader. AB - Full-length simian hemorrhagic fever virus (SHFV) genome RNA (about 15 kb in length) and six subgenomic RNAs, ranging in size from 0.65 to 4.7 kb, were detected by Northern blot hybridization in MA104 cytoplasmic extracts with a 3' genomic antisense probe. The 5' regions of the two smallest subgenomic RNAs (RNAs 6 and 7) were cloned and sequenced. Sequence analysis indicated that these two RNAs contained a common 5' leader sequence joined to the subgenomic RNA bodies via a highly conserved junction sequence; the junction sequence of RNA 7 was 5' TTAACC-3', while that of RNA 6 was 5'-TCAACC-3'. The complete 5' leader sequence (208 nt) was obtained from genomic RNA. The genomic 5' junction sequence is identical to that of RNA 7. Northern blot hybridization with an antisense 5' leader probe confirmed the presence of the complete leader sequence in all six species of subgenomic RNA. In its virion morphology, genome size, gene order, and replication strategy, SHFV is most similar to viruses such as equine arteritis virus, lactate dehydrogenase-elevating virus, and Lelystad virus/porcine respiratory and reproductive syndrome virus. PMID- 7886958 TI - Sequences in the preC region of duck hepatitis B virus affect pregenomic RNA accumulation. AB - The pregenomic RNA of hepadnaviruses serves as both the mRNA for the core and polymerase proteins and the RNA template for reverse transcription. We have identified a region in the duck hepatitis B virus pregenomic RNA transcription unit that is critical for the accumulation of this transcript. This 85-nt region, termed alpha, is located within the preC region; deletion of alpha results in drastically reduced steady-state levels of pregenomic RNA. This effect is not due to reduction in transcription initiation or to enhancement of premature polyadenylation at the 5' copy of the viral poly(A) signal. However, this phenotype is suppressed by deletion of a second, larger region (beta) located ca. 1 kb downstream. The activity of the alpha element is tissue- and species nonspecific; however, it displays absolute orientation-dependence and its activity is influenced by its position within the transcript. Models for its action are discussed. PMID- 7886959 TI - Hypermutation of the phosphoprotein and altered mRNA editing in the hamster neurotropic strain of measles virus. AB - Sequence analysis of the nucleoprotein and phosphoprotein (P) genes of viruses in the hamster neurotropic lineage of measles virus revealed that the neurotropic variants are quite different from the Philadelphia 26 progenitor strain. In Vero cells persistently infected with the hamster neurotropic strain, predicted changes occur in 5.0% of the nucleoprotein and 8.1% of the P amino acids and some of these changes appear to affect the relative electrophoretic mobility of each protein. To evaluate one aspect of the viral polymerase complex containing these mutations, the distribution of P mRNA editing in each of the three strains was determined by both cloning and sequencing of polymerase chain reaction-amplified DNA fragments which included the editing site and by primer extension analysis of viral mRNA. Editing of P mRNA in the neurotropic strains shows a shift away from the single G insertion product to those with greater than 2 Gs inserted. The altered editing distribution has implications for the role of transcriptional regulation in measles virus persistence. PMID- 7886960 TI - Identification of a coat protein binding site on southern bean mosaic virus RNA. AB - The cowpea strain of Southern bean mosaic virus (SBMV-C), a T = 3 icosahedral RNA virus, was dissociated to yield a ribonucleoprotein complex (RNPC) composed of the viral RNA and coat protein subunits. To determine if the coat protein subunits were bound to a specific site on the viral RNA, the RNPC was treated with ribonuclease, and the remaining coat protein--RNA complexes were recovered by filter binding. A single species of RNA was isolated by this procedure and further characterized by sequencing. The RNA was mapped to nucleotides 1410-1436 of the SBMV-C genome. This region of the viral RNA was predicted to fold into a hairpin with a 4-base loop and a duplex stem of 24 nucleotides. The stability and specificity of the coat protein-RNA complex isolated from dissociated virus suggest a possible role for this interaction in the selective encapsidation of the viral RNA. PMID- 7886961 TI - The putative replicase of the cocksfoot mottle sobemovirus is translated as a part of the polyprotein by -1 ribosomal frameshift. AB - The polyprotein of cocksfoot mottle sobemovirus (CfMV) is encoded by two overlapping open reading frames (ORF). The ORF 2a codes for the putative VPg and serine protease and the ORF 2b codes for the putative replicase. The consensus signals for a -1 ribosomal frameshifting event are found at the very beginning of the overlapping region of these ORFs. The shifty heptanucleotide in CfMV is UUUAAAC, and the secondary structure after the shifty sequence is predicted to be a stem-loop. In vitro translation of the CfMV RNA in wheat germ extract produced proteins of several sizes, including one of 100 kDa. According to the nucleotide sequence data, no single ORF is capable of directing the synthesis of a 100-kDa protein. A chimeric beta-glucuronidase-CfMV cDNA containing the entire ORF 2a and 2b overlap region including frameshift signals was constructed. A trans-frame protein of 108 kDa was produced from this construct with an efficiency of 26-29% by in vitro translation in wheat germ extract. CfMV is the first sobemovirus in which the putative replicase is reported to be produced as a part of a polyprotein by a -1 frameshift event. The replicases of the sobemoviruses are related to the luteovirus subgroup II replicases, which are known to be produced by -1 ribosomal frameshift. The reported amino acid sequences of the putative replicases of sobemo- and subgroup II luteoviruses were compared to that of the putative replicase of CfMV. This comparison revealed more extensive homology between these groups than previously reported. PMID- 7886962 TI - Identification and characterization of a second putative origin of DNA replication in a baculovirus of Orgyia pseudotsugata. AB - A 7.5-kb region (96.8-2.5 m.u.), called Op5, of the Orgyia pseudotsugata multinucleocapsid nuclear polyhedrosis virus (OpMNPV) genome that contains an origin of DNA replication was characterized. This region replicates several times more efficiently and is unrelated to the previously identified putative origin of replication located on the viral HindIII-N fragment. In contrast to HindIII-N, the origin on Op5 contains repeated sequences with limited sequence identity to the homologous regions from AcMNPV. In isolation, these repeated sequences were not sufficient for origin activity in OpMNPV-infected Lymantria dispar cells, but required an additional 1.3 kb of sequences located to the left of the repeats. Four regions of the OpMNPV genome that crosshybridize with the repeated region were also found to replicate in our infection-dependent DNA replication assay. A deletion clone of Op5 that replicates efficiently in OpMNPV-infected L. dispar cells, was found to replicate at less than 2% the replication level of AcMNPV hr2 in AcMNPV-infected Spodoptera frugiperda cells. PMID- 7886963 TI - Phylogenetic analysis of primate foamy viruses by comparison of pol sequences. AB - The relationship between primate foamy viruses was determined by comparing a 425 bp DNA segment obtained by PCR using primers homologous to highly conserved portions of the pol gene. The phylogenetic tree of 14 foamy viruses investigated reflects the relationship between their host species: A cluster of Asian Old World monkey foamy viruses including simian foamy virus (SFV) prototypes 1 and 2 (isolated from Macaca cyclopsis) is separated from African Old World foamy viruses including prototype SFV-3 and SFV-3 strain LK-3 (isolated from African green monkeys, Cercopithecus aethiops). These two clusters of Old World monkey foamy viruses are more distantly related to a cluster of ape and human foamy viruses including prototypes SFV-6, SFV-7, SFV cpz (all isolated from chimpanzees), and human foamy virus (HFV). The New World prototype SFV-8 (isolated from a spider monkey, Ateles sp.) is distinct from the Old World cluster. Our own foamy virus isolates from a rhesus monkey (Macaca mulatta) and an African green monkey were grouped to the Asian or the African Old World monkey foamy virus cluster, respectively. The foamy virus sequences obtained from lymphocytes of two humans, one exposed to African green monkeys and the other to cultured HFV, were compared. The first sequence was closely related to the African Old World monkey foamy virus cluster, whereas the second was identical to HFV, except for a single mismatch. We conclude that limited sequencing of amplified DNA is a powerful tool for classification as well as molecular epidemiology of foamy viruses. PMID- 7886964 TI - [Genome sequence and antigen structure of the Powassan virus: analysis of genetic elements of tick-transmitted flaviviruses]. PMID- 7886965 TI - [Detection of trisomy 12 in chronic lymphatic leukemia (CLL) using polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). A comparison]. PMID- 7886966 TI - [Comment on the contribution: Adlassnig, K.-P.: Medical informatics in research, education and patient management]. PMID- 7886967 TI - [Transmission of HIV infection]. AB - The increasing number of human immuno-deficiency virus (HIV) infections and the shift from traditional risk groups to the general population give reason for reviewing the routes and risks of virus transmission. In Africa HIV is transmitted mainly by heterosexual contact; in Europe and the USA homosexuality is still the leading cause of infection, however, heterosexual transmission is increasing dramatically. The heterogeneity of HIV strains and host factors may contribute to the progression of HIF infection to AIDS. Vaginal fluid and sperm are infectious, ulcerations caused by venereal diseases and some sexual practices increase the risk of HIV transmission. The use of condoms reduces the risk of infection, but does not eliminate it completely. Saliva is not a likely source for HIV transmission, but oral sex is a risk factor. HIV transmission from mother to child can occur either in utero, during delivery or by infected breast milk. Intravenous drug abusers still get infected by needle sharing. The risk of infection due to therapy with blood products can be minimized by anti-HIV antibody testing, neopterin screening, and virus inactivation. Cell-free blood products can be effectively heated and/or treated with solvent/detergent mixtures. Virus inactivation in fresh frozen plasma is not yet possible. PMID- 7886968 TI - HIV-testing of health care workers: unethical request or moral obligation? AB - Transmission of HIV from physician to patient is possible. Physicians should help the public understand the low level of this risk and put it in the perspective of other medical risks, while acknowledging public concern. Nevertheless, there is a clear need for national guidelines which give unambiguous, practicable guidance about HIV-testing of health care workers performing invasive procedures and consequences of positive results. It is an ethical obligation of us physicians to come forward with such distinct recommendations and clearly have identified "exposure-prone" procedures which might necessitate HIV-screening. Infection with HIV does not in itself justify restrictions on the practice of an otherwise competent health care worker, but seropositive physicians should place themselves under the guidance of an expert review panel, which should determine whether practice restrictions are appropriate. PMID- 7886969 TI - [Idiopathic CD4+ T-lymphocytopenia in 2 patients without indications for HIV infection]. AB - We report on two patients with idiopathic CD4+ T cell depletion. A 26 year-old woman presented to us with acute respiratory failure requiring mechanical ventilation. Despite combined antibiotic therapy parenterally the opacities increased in the chest X-ray. An open lung biopsy was performed and led to the histological diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP). Respiratory function was improved impressively by high dose parenteral cortisone administration. This patient showed a general lymphocytopenia with severe CD4+ T cell depletion (60(37%)/mm3 blood). The CT4+ T cell concentration increased during a follow up period of 14 months, but did not reach normal values. The second patient was a 33 year-old homosexual. He was admitted with a mucocutaneous fungal infection which was successfully treated by antifungal drugs. This patient demonstrated a transient CD4+ T cell depletion (350(32%)/mm3 blood). In both patients HIV type 1 and 2 infections were excluded by antibody- and p 24-antigen testing, polymerase chain reaction and virus culture. CONCLUSION. Idiopathic CD4+ T lymphocytopenia differs from HIV infection in immunological profile, in the tendency to reversal of the CD4+ T cell depletion over time and in its better prognosis. It is unclear if this is a new syndrome and whether a transmissible agent, or possibly a genetically-determined reaction to noxious agents is responsible. PMID- 7886970 TI - Are referring physicians satisfied with endoscopy reports? AB - To assess the opinions of referring physicians on the contents of endoscopy reports, 150 consecutive endoscopy reports were accompanied by a questionnaire. Of these, 102 reports were returned: response was 68%. Almost half of the reports were considered not fully satisfactory. However, endoscopy reports may be improved by including information such as indication, therapy plan and follow-up plan on a more regular basis, and add clarity whether findings may account for complaints of the patient. To tailor endoscopy reports to the needs of individual referring physicians, more explicit information of referring physicians is required. If endoscopists are responsible for the information they provide to the referrer, it is also their task to facilitate the explicit formulation of preferences by the referrer. PMID- 7886971 TI - Double blind placebo controlled study on the effect of the nitric oxide donor molsidomin and the 5-HT3 antagonist ondansetron on human esophageal motility. AB - The aim of the present study was to investigate the effects of acute administration of the NO-donor molsidomin (2 mg) and the 5-HT3 antagonist ondansetron (8 mg) on esophageal motility and lower esophageal sphincter pressure (LESP) in 10 healthy volunteers by stationary side hole manometry in a double blind placebo controlled study design. LESP, contraction amplitudes (5, 10, 15 cm above the LES) and propagation velocity (10-15 cm above the LES) for dry and wet swallows were analysed and additional blood samples were taken for determination of plasma levels of VIP and gastrin. Molsidomin significantly decreased basal LESP from 16.8 +/- 1.6 mmHg to 11.4 +/- 1.0 mmHg, while ondansetron had no influence. Molsidomin also reduced contraction amplitudes of dry swallows (saline 61.9 +/- 7.2 mmHg, molsidomin 40.1 +/- 8.1 mmHg), while it did not influence contraction amplitudes of wet swallows. Ondansetron had no effect on contraction amplitudes. Both substances did not influence propagation velocity of wet swallows, while they reduced propagation velocity of dry swallows significantly (saline 3.9 +/- 0.4 cmls, ondansetron 3.1 +/- 0.2 cm/s, molsidomin 3.1 +/- 0.2 cmls). There were no effects on plasma levels of gastrin or VIP. These data strongly suggest a possible therapeutic role of molsidomin in the treatment of esophageal motility disorders. Effects of ondansetron have to be further evaluated in patients with disturbed esophageal motility. PMID- 7886973 TI - Crohn's disease with Behcet's syndrome like appearance: a case report. AB - The differential diagnosis of Behcet's syndrome or Crohn's disease can be extremely difficult. In this case report we present a 32-year old female patient with Crohn's disease. The coexisting extraintestinal symptoms such as mucocutaneous apthous lesions of the mouth and vulva, the erythema nodosa of the lower extremities and recurrent arthralgias made the correct diagnosis even more difficult. The patient was treated with a combination of systemic corticosteroids and azulfidine enema, under which she recovered. PMID- 7886972 TI - Prevalence of gastrointestinal symptoms in diabetic patients and non-diabetic subjects. AB - To determine the frequency of gastrointestinal symptoms in diabetic patients, 190 patients, consecutively referred to the Diabetes Research Institute, reported their gastrointestinal symptoms on a standardized symptom list. One hundred and eighty non-diabetic healthy subjects served as (matched) controls. Finally, 75 patients with Type 1 (insulin-dependent) diabetes mellitus (33 male, 43 female; age 34,1 (18-60) yrs, diabetes duration: 11,1 (0,3-41) yrs) and 68 patients with Type 2 (non-insulin-dependent) diabetes mellitus (31 male, 37 female, age: 61,4 (37-88) yrs, diabetes duration: 10,7 (0,3-40) yrs) were studied and compared with two cohorts of controls of the same size. There were no differences in prevalence of symptoms referrable to the upper and lower GI-tract in type 1 diabetic patients as compared with controls. Among patients with type 2 diabetes the main gastrointestinal complaint was constipation (22,1% vs 10,3%; p < 0.05). Upper gastrointestinal symptoms were also more frequent among Type 2 diabetic subjects (nausea 11,8% vs 2,9%, p < 0.05). There was a tendency for an increased symptom prevalence with higher age in both type 1 and type 2 diabetes. Presence of peripheral neuropathy was associated with a higher symptom prevalence in type 1 diabetes. After stratification, diabetes duration and glycaemic control (HbA1c) did not influence the frequency of symptoms. Thus, gastrointestinal symptoms occur frequently among both diabetic patients and non-diabetic subjects. However, significant differences were found only in type 2 (non-insulin-dependent) diabetes, the commonest symptom being constipation. These findings support the need of a nondiabetic control group in epidemiological studies evaluating symptom prevalence in diabetes mellitus. PMID- 7886974 TI - Hereditary pancreatitis--a case report. AB - A female patient with hereditary chronic pancreatitis is described. She presented initially at the age of 18 years with abdominal pain due to acute pancreatitis. Predisposing etiological factors were not recognized. During the ensuing years she had recurrent episodes of abdominal pain and chronic pancreatitis with extensive pancreatic calcifications was finally demonstrated. Six other family members within three generations were affected by chronic pancreatitis suggesting an autosomal dominant mode of transmission. None of the affected patients showed signs of diabetes mellitus, aminoaciduria or hyperparathyroidism. PMID- 7886975 TI - [Recent therapeutic modalities in chronic inflammatory bowel diseases: 4- or 5 aminosalicylic acid?]. AB - In search of new therapies in IBD, the introduction of 4-aminosalicylic acid (4 ASA) has been proposed based on the longstanding, positive clinical experience in tuberculosis, the expected similar modes of action due to the close structural analogy to 5-aminosalicylic acid (5-ASA), an established therapy in IBD, and its inexpensiveness. To better understand the mechanisms of action of aminosalicylates, the intestinal inflammatory response and to develop new, more effective and cost saving drugs it is important to compare 4-ASA with 5-ASA with respect to their pharmacology, mechanisms of action and clinical efficacy. The inhibition of the upregulation of the initial local immune response, the inhibition of the production of inflammatory mediators, e.g. leukotrienes and the direct scavenging of toxic oxygen metabolites are important common antiinflammatory mechanisms. As the clinical experience with 4-ASA is promising, but still limited, 4-ASA currently cannot yet be recommended outside clinical trials. As the costs of 4-ASA are significantly lower compared to 5-ASA, 4-ASA may replace 5-ASA in the near future provided further trials will confirm the therapeutic and pharmacologic equivalency. PMID- 7886976 TI - [Fibrolamellar carcinoma]. AB - Fibrolamellar carcinoma (FL-Ca) is a primary malignant liver tumor at unknown etiology, without cirrhosis and usually without an increase at tumor markers, which occurs mainly in young patients. As it can simulate malignant and benign tumors, particularly FNH, diagnosis is difficult. Ultrasound and angiography show mostly uncharacteristic features. The highest specificity has CT, if calcifications are present, because these calcifications in a tumor similar to FNH are pathognomonic for FL-Ca. In MRI the central scars of FL-Ca and FNH have a different signal intensity in T2-weighted images, so that MRI becomes more and more important in the differential diagnosis to FNH. PMID- 7886977 TI - [Chimerism in recipients of organ transplants]. PMID- 7886978 TI - [Nicotine for ulcerative colitis--a new therapeutic principle?]. PMID- 7886979 TI - Relationship between oxidative hepatic metabolism, urinary sodium excretion and sympathetic nerve activity in experimental cirrhosis in the rat. AB - This study investigated the relationship between changes in renal sympathetic activity as assessed by renal norepinephrine spill-over and the onset of renal sodium retention in the phenobarbital/carbon tetrachloride model of experimental cirrhosis in rats. In this model, sodium retention occurs when hepatic function, assessed by the aminopyrine breath test (ABT), falls below a critical threshold. Three groups of rats, studied on a constant salt diet, included a group with cirrhosis and sodium retention, a group with cirrhosis of similar duration and no sodium retention and a time-control phenobarbitaltreated group. ABT, renal plasma flow (RPF), glomerular filtration rate (GFR) and mean arterial pressure (MAP) were measured at the time of catecholamine sampling in anesthetized rats. Cirrhosis was associated with reductions in MAP, no change in RPF and GFR, and an ABT below the threshold in rats with sodium retention. In contrast, rats without sodium retention had liver function above the threshold. Renal norepinephrine spill-over increased continuously from controls to non-sodium retaining and sodium retaining animals. The difference between sodium retaining animals and controls was significant. Norepinephrine spill-over correlated to ABT and MAP but not urinary salt excretion. The data suggest that, under these experimental conditions, increased sympathetic activity may contribute to the onset of sodium retention. A plausible explanation for the continuous increase is that catecholamines are released as a compensatory mechanism in response to a primary yet undefined vasodilator. PMID- 7886980 TI - Non-operative management in a case of spontaneous splenic rupture in infectious mononucleosis. AB - Spontaneous splenic rupture as a complication of infectious mononucleosis was diagnosed in a 19-year-old woman. Sonographic and MRI investigations revealed subcapsular hematoma of the spleen without overt rupture. The patient was managed conservatively. Somatostatin treatment was initiated in order to reduce splanchnic blood flow. Further clinical course of the patient was favourable. Seven days after the diagnosis of splenic rupture the patient was discharged from hospital. Non-operative management should be considered in patients with subcapsular splenic rupture to avoid complications of splenectomy (e.g. post splenectomy sepsis). PMID- 7886981 TI - [Surgical therapy of short bowel syndrome]. AB - Advances in medical and surgical technique and the development of home parenteral nutrition have led to an increasing number of patients with short-bowel syndrome. Many patients could benefit from definite surgical therapy as long-term parenteral nutrition besides being expensive frequently causes severe complications. Various techniques to prolongate intestinal transit and increase the absorptive area of the remaining small bowel have been experimentally developed and some have been successfully employed in humans. The recent discovery of new potent immunosuppressive agents has initiated clinical endeavours at intestinal transplantation. The various techniques for the surgical therapy of short-bowel syndrome with their indications and potential risks are reviewed. PMID- 7886982 TI - [Improving the effect of orthograde colonic lavage with golytely solution by adding dimethicone]. AB - The effectiveness of an additional application of Simethicone during an orthograde lavage with Golytely solution in preparation for colonoscopy was tested in a prospective, randomized, placebo-controlled double blind study on 152 patients 78 Simethicone, 74 placebo). The colon regions were separated into rectosigmoid, descending colon, transverse colon and ascending colon and interpreted according to the criteria formation of foam and contamination with feces. By the endoscopic examination of the colon we found a statistically significant improvement in visibility in the patients treated with Simethicone in contrast to placebo both in the individual scores, separated according to each of the colon regions, and in the total scores (p < 0.01). Furthermore, the time needed for the colonoscopy could be significantly shortened in the Simethicone group (p < 0.05). Adverse effects were not observed. We conclude that the additional application of Simethicone during the orthograde colon lavage with Golytely solution results in an improvement in the preparation for the colonoscopy as well as visibility of the colon mucosa. PMID- 7886983 TI - [7B2--the first neuroendocrine chaperone]. PMID- 7886984 TI - [Is routine endoscopic monitoring for prevention of carcinoma in ulcerative colitis of value?]. PMID- 7886985 TI - [Acute variceal hemorrhage: status of drug therapy]. PMID- 7886986 TI - Polyethylene glycol 4000 for slow transit constipation. AB - Slow transit constipation is notoriously difficult to treat. We tested whether polyethylene glycole 4000 (PEG) improves slow transit constipation. Eight female outpatients with symptoms of constipation and a colonic marker transit of more than 60 h were included (age 46 +/- 4y, duration of complaints 17 +/- 3y) in a randomised controlled cross-over study. During a 6-week placebo and 6-week PEG phase (60g PEG/d) the following parameters were measured: 1. subjective well being with respect to defeacation on a visual analogue scale (-8 cm very bad, +8 cm very good), 2. in the first 5 weeks of each phase, average dose of sodium picosulfate (prescribed as only allowed laxans, dose adjusted and protocolled on a diary by patient) 3. stool frequency, 4. colonic transit of radiopague polythene pellets in the last week of each phase (the use of laxative was strictly prohibited in this last week). Both subjective and objective parameters of colonic function improved significantly. Visual analog scale ratings improved from -4.65, [-8; 0.5] to 4.65, [-8; 7.5]cm (median, range) (p = 0.028), the self administered dose of sodium picosulfate decreased from 4, [0; 37] to 0, [0; 11] drops per day (p = 0.028), stool frequency increased from 3.1, [1; 30] to 11, [2; 33] defeacations per week (p = 0.017), and total colonic transit decreased from 91, [67; 116] to 43 h, [17; 76]h (p = 0.017). In conclusion, PEG improves colonic function in patients with slow transit constipation subjectively and objectively. PEG should be considered as an additional option in patients refractory to established forms of treatment. PMID- 7886987 TI - Production of interleukin-1b and tumor necrosis factor--a by peripheral blood human mononuclear cells in active and inactive stages of ulcerative colitis. AB - The production of Interleukin-1b (IL-1b) and Tumor necrosis factor a (TNF-a) by peripheral blood human mononuclear cells has been measured by an enzyme linked immunosorbent assay in 49 patients with ulcerative colitis (UC), 16 patients with first onset of the disease, 15 with untreated active disease, 18 patients with active UC under treatment and 14 healthy control subjects. IL-1b and TNF-a values were significantly higher (p < 0.001) in all groups of patients with active disease comparing to values after the achievement of remission or healthy controls. This increase was more profound in patients with pancolitis, in all groups with UC in active stage, when a comparison was made with rectosigmoiditis patients (p < 0.05). These results point towards a correlation between IL-1b and TNF-a production in UC patients and activity and extent of the disease. PMID- 7886988 TI - [Depression in children and adolescents]. AB - The prevalence of major depression in preschool is less than 1 procent, in school age children about 2 percent, and in adolescents about 4.7 percent. While as no significant sex differences have been reported among preadolescents, studies of adolescents have reported 2 to 3 times higher rates of depression. The most frequent course of depression is chronic and persistent, the mean length of depressive episode being 30 weeks. Depressed children and adolescents have impaired psychosocial functioning and school problems. Relapse occurs at a high frequency for depressed patients. The high recurrence of depression in children and adolescents calls for a long-term management in these age-groups. PMID- 7886989 TI - [Quality of life: assessment instruments and results]. AB - The article reviews instruments for measuring quality of life which are mainly used for the assessment of psychosocial impact of cancer and tumor illnesses. An early assessment of the psychosocial consequence of illnesses which are carried out during the interviews are given in addition to the questionnaires. Newer, multidimensional data-collections are described in detail. PMID- 7886990 TI - [Children of alcohol and drug dependent families. Developmental risks and prevention]. AB - Developmental risk mainly refers to the development of emotional and behavioral disturbances, and a tendency to consume drugs in children with parental drug dependence. Results of empirical studies have indicated that the ingestion of drugs and alcohol has an effect on the development of behavioral disturbances (aggression, hyperactive), social anxiety and uncertainty. Intervention programs will be gradually developed to stabilize the children at risk. PMID- 7886991 TI - [The family background of bulimic women. An intercultural comparison of Austrian and American students]. AB - Although various familial factors have been thought to influence the development and outcome of bulimia nervosa, no cross-cultural studies have examined familial factors in this disorder. To provide more data in this area, we compared 33 female college students with bulimia nervosa in Innsbruck (Austria), and 33 female college students with bulimia nervosa in Boston (USA), on several aspects of family background. These indices includes weight history and diet behavior of family members; psychiatric disorders among family members; intrafamilial relationships; types of and attitudes toward upbringing; sexual attitudes among family members; and experiences of physical and sexual abuse during childhood. We found few significant differences between the two groups on these indices. However, American bulimic women reported their family members to be more overweight, significantly more likely to be on a diet, and more likely to display a lifetime diagnosis of major depression than the family members of Austrian bulimic women. The findings of this study add to the literature and family background in bulimia nervosa, and suggest several avenues for future research for crosscultural studies in this area. PMID- 7886992 TI - [Diagnosis in psychotherapy. Results of a survey of diagnostic practices of psychotherapy trained psychologists]. AB - In a representative survey concerning the current status and future perspectives of psychological assessment procedures, psychologists trained as psychotherapists were investigated with respect to their diagnostic activity within the framework of psychotherapy. The analysis aimed both at providing insights into the practice of test application among psychotherapeutically active psychologists and at determining the extent to which their diagnostic activity is influenced by the existing debiting procedures with health insurance companies. The results did not indicate any differences in the relevant aspects of the investigation between psychotherapists who did and those who did not debit health insurance companies. PMID- 7886993 TI - [Survey of materials in hip endoprosthesis]. AB - While bone cement debris has been recognised as an important factor in aseptic loosening of prosthetic components, the interest is now focused on the impact of debris and wear-off particles from polyethylene and metal alloys. As an optimal lubrication cannot be generated yet, direct contact between the components produces wear particles, depending on the materials used. The materials reported on include alloys based on iron, cobalt, titanium and polyethylene, bone cement and ceramics. These all show the problem of debris, friction, corrosion (except ceramics) and load failure, related to the work up process. The practitioner is given an overview and tables are presented to compare the used material. PMID- 7886995 TI - [Exchange of endoprosthesis using a proximal femur resection prosthesis]. AB - Total hip arthroplasty (THA) with the use of a Mega prosthesis was performed on 24 patients with significant loss of bone stock in revision THA. A clinical and radiological examination was carried out according to the Enneking evaluation scheme on average 7 years after THA. Pain, active hip motion and strength of hip muscles, walking ability, and activities of daily living rated excellent or good and compared well with the results following conventional THA. Limp and positive Trendelenburg sign were common to all except one after Mega prosthesis implantation and were independent on the type of refixation of the hip abductors. Dislocation of the prosthesis occurred in 16.6% of cases and depended on the type of cup implanted. Remarkable was a periprosthetic callus formation surrounding the stem of the femoral implant. PMID- 7886994 TI - [Adaptation osteotomy in idiopathic femoral head necrosis]. AB - Thirty-nine patients who suffered a segmental ischemic necrosis of the hip, fifteen of which affected on both sides, were treated with osteotomy of the femur. The re-examinations were carried out after an average period of 6.6 (2.5 12) years. While in twenty one cases, the hip necrosis was treated exclusively by varisation, in thirty three cases a combination of varisation and flexion was effected. 12 patients (equivalent to 22.2%), all of them with a necrotic angle of more than 115 degrees, were provided with a total hip arthroplasty in the interval. The patients with a necrotic angle smaller than 115 degrees showed a definite alleviation of the pain symptoms, an increased hip flexibility and an improved locomotory pattern. PMID- 7886996 TI - [The importance of roentgenological and scintigraphic studies in patients with and without thigh pain following cementless PCA hip endoprosthesis]. AB - Persisting postoperative thigh pain is a common problem in cementless total hip prostheses occurring in a rate of about 15-20% of the patients. The reason for that phenomenon has not become clear so far. In a clinical, radiological and scintigraphic study 70 patients with 81 PCA cementless total hips were randomized in groups with (n = 34) and without significant thigh pain (n = 36). All patients underwent clinical examination including a standardized questionnaire, x-ray and 3-phase bone scintigraphy. Quantitative assessment of Tc-99m-MDP uptake was made. In the group of patients with persisting thigh pain the scintigraphic analysis showed an significantly increased uptake at the tip and the medial and lateral femur. These findings could not be correlated with clinical loosening of the prosthesis. Slight or moderate uptake in the area of the greater and lesser trochanter as well as the tip was a common finding in PCA prosthesis in all patients. In the radiological analysis no difference between both groups was evident. The study showed that patients with thigh pain after cementless PCA total hip prosthesis have specific regions of significantly increased uptake in scintigraphic examination (tip, medial and lateral femur), which cannot be correllated with clinically or radiologically signs of loosening. The morphologic reasons for the thigh pain remain unclear. PMID- 7886997 TI - [Sports fitness of active handball and soccer players with anterior instability of the knee joint]. AB - Based on an epidemiological study of 582 active handball and soccer players the abilities and limitations were analysed for sports activities of 24 athletes with an ACL-deficient knee. 22 of the 24 athletes suffered from a straight anterior instability. 50% attempted to avoid cutting mechanisms. The level of motivation was better than in the whole population. Handball players could continue their sports better and longer than soccer players. However, 19 athletes had to be classified as "knee-abusers" because they continued their sports inspite of having complaints. If athletic participation following ligament injuries of the knee should be rated, an accurate quantification and qualification is imperative. PMID- 7886998 TI - [Demonstration of the blood supply of human cruciate ligaments using the plastination method]. AB - The blood supply of the attachment regions of the anterior and posterior cruciate ligament is demonstrated in 14 cadaver knees by the plastination method. Our findings demonstrate the blood supply by vessels of the synovium. The direct attachment to the bone is free of vessels. Anastomoses between the synovium and the periosteum could be found. In conclusion the surgical coverage of ligament reconstruction and of ligament transplantation by synovium is recommended when ever possible to permit the ingrowth of revascularisation vessels. PMID- 7886999 TI - [Sonographic diagnosis of the juvenile tarsus. Clinical application possibilities demonstrated by examples]. AB - Radiologic assessment of foot deformities in young children is limited especially by the ossification status. Ultrasonography proved to be a useful diagnostic supplement e.g. in idiopathic talipes equinovarus, vertical talus, and tarsal coalitions. Effects of treatment and three-dimensional movements of the tarsal joint complex can be delineated. Sonographic assessment of tarsal alignment is applicable already in the first months of life. This study deals with first experiences in clinical application of this new diagnostic technique. PMID- 7887000 TI - [Congenital round talus]. AB - The collective consists of 11 patients with a "ball and socket"-anomaly of the talus with a mean age of 13.7 years. All patients demonstrated typical symptoms of the FFU-syndrome with a leg length discrepancy of 4.3 cm (2-20). In 6 patients a close follow-up was done in the early development of the talus form. In the metacarpal region also synostosis of some bones were seen at a mean age of 4.8 years (3.2-5.9). No clinical complaints but a slight reduction of hind foot mobility could been registered. Ball and socket deformity can not been seen as congenital, but as a subsequent deformity after congenital fusions in the metatarsal bones. PMID- 7887001 TI - [Intermediate results following subcapital metatarsal osteotomy in the therapy of hallux valgus with metatarsus primus varus]. AB - 71 feet were investigated after subcapital modified osteotomy of the metatarsus according to Kramer for an average follow-up period of 19 months. Mean improvement of the Hallux valgus angle was 10 degrees whereas the intermetatarsal angle was improved by 4 degrees on average. The high degree of satisfaction of patients (83%) with the outcome of this surgical method suggest its application in cases of medium metatarsus primus varus within hallux valgus deformations when the metatarso-phalangeal joint is not affected. In patients aged 50 years and older as well as in cases of MT I varus exceeding 18-20 degrees this operation should strictly be limited to the cases indicated above. PMID- 7887002 TI - [Biomechanic results in impingement syndrome of the shoulder]. AB - Forces underneath the coraco-acromial vault during elevation of the arm were evaluated with a dynamic shoulder model. The deltoid muscle and the rotator cuff muscles were simulated with a hydrodynamic device, in ten autopsy specimens. Controlled cycles of glenohumeral joint motion were initiated with computerised regulation. An ultrasonic device measured the position of the arm in all spatial orientations. Capacitive sensors recorded forces underneath the coraco-acromial vault. The mean force during one cycle of elevation averaged 13.9 Newton +/- 12.5 Newton underneath the coraco-acromial ligament and 3.44 Newton +/- 4.37 Newton underneath the coracoid process. The peak force averaged 37.8 Newton +/- 33.2 Newton underneath the acromion, 3.03 Newton +/- 2.62 Newton underneath the coraco acromial ligament and 6.93 Newton +/- 7.38 Newton underneath the coracoid process. The force markedly increased at the final stage of arm elevation and during early reverse-elevation in most specimens, corresponding to the painful arc sign. In some specimens, the force under the coracoid process exceeded the force under the acromion. Osteophytes protruding into the subacromial space may lead to a concentration of force and to high regional pressures. PMID- 7887003 TI - [Function of the glenohumeral ligaments in active protection of shoulder stability]. AB - We harvested the joint capsule, the glenohumeral ligaments, and the coracohumeral ligaments of 8 fresh formalin-preserved shoulder specimen. We made use of the van Gieson technique and a special silver impregnation for staining peripheral axons according to Nowotny. The ligaments were cut into slices with a thickness of 15 microns. In total we performed 10,000 cuts. We discovered axons in all ligaments. These axons had no relation to vessels or vessel walls. Besides these axonal structures we detected type II mechanoreceptors (Pacini receptor). CLINICAL SIGNIFICANCE: The neural structures discovered in the glenohumeral capsule are of clinical importance especially in consideration of the high account of recurrent shoulder dislocation and concomitant Bankart lesions. Receptors located in the glenohumeral ligaments might control the stabilizing shoulder musculature. On this premises, rupture or detachment of these ligaments will lead to a loss of the feedback mechanism. PMID- 7887004 TI - [Arterial vascularization of the bony acetabulum]. AB - The arterial supply of the acetabulum is studied in 30 human hip-pelvis specimens utilizing conventional angiography, 3 D-CT and maceration. 3 specimens out of 30 had to be excluded due to extravasation and incomplete filling. The arteries of the pelvis were filled with barium sulfate in 16 cases and in 11 cases with a solution of resin and lead powder. Conventional angiograms were performed in all specimens. In preparations with resin/lead powder additional CT with 3 D reconstructions of the surface of the acetabulum and arteries were done. 3 D-CTs show precise relationship of the arteries to the acetabulum. Filling with resin and lead powder is optimal for anatomical studies. It permits comparative 3 D-CT and conventional X-ray examination and subsequent preparation of the vessels in corrosion technique. The central parts of the acetabulum are vascularized by the obturator artery, the cranio-lateral part by the a. glutea superior and the ischial parts by the a. glutea inferior. The arterial supply of the acetabulum can be saved knowing the way and entry of the arteries into the bone. This is of importance for triple osteotomies of the pelvis but as well for difficult total hip replacements and revisions. The described method can be used for anatomical studies of the vessel to bone correlation in different anatomical sites. PMID- 7887005 TI - [Humerus lengthening in a unilateral technique: case report]. AB - Surgical lengthening of the humerus is indicated for cosmetic and functional reasons. The discrepancy should exceed 4 cm. Complications (review of literature) and our own experience regarding lengthening of extremities indicate that surgical lengthening of the humerus is technically feasible and reasonably safe. It appears to have fewer risks and complications than surgical lengthening of the femur or the tibia; even though radial nerve paralysis is an important complication. PMID- 7887006 TI - [Osteoid osteoma of the hand. Case representation with special reference to magnetic resonance tomography and litrature review]. AB - The pre-operative diagnosis of osteoid osteoma of the first metacarpal bone was suggested by Magnetic Resonance Imaging in a 15 year old girl. As indicated in the literature, osteoid osteoma of the hand is relatively rare. The symptoms and the x-rays features of osteoid osteoma are essentially independent from the location consisting in rather unspecific pain and radiographically osteolytic nidus surrounded with sclerosis. In the few published cases with MR Imaging, the nidus shows high signal intensity surrounded by low signal intensity in the area corresponding to the radiographically visible sclerosis. PMID- 7887007 TI - [Analysis of strength values of the wrist muscles and its clinical relevance]. AB - A lot of injuries in profession and sports concern the hand. Therefore first principles should be elaborated which make it possible to assess such an injury and to define the therapy progress. Concerning this 50 probationers underwent an isokinetic test of the wrist extensors and of the wrist flexors. A close correlation could be determined between torque and work. The highest torque were achieved with the lowest velocity. Dependences could be found out concerning, age and dominant hand, so that these factors have to be considered with an assessment of an injury. PMID- 7887008 TI - [Software and system-induced errors in isokinetic force measurements]. AB - In the literature a good reliability of isokinetic measurements is reported. In spite of these reports high variations of the peak torque and work values were registered when testing 24 patients with low back pain, using a CYBEX TR isokinetic trunk rotation apparatus. After a 3 week's training the patients force (peak torque) increased in the average between 10.7 p.c. (SD +/- 26.4) and 23.2 p.c. (SD +/- 63.8), corresponding to the test-velocity. Seven of the 24 patients improved or deteriorated more than 30 p.c. Analysing the parameters which could interfere with the results there was found a discrepancy between the original CYBEX software and the German Iso-Kin 4.0 software. The Isokin 4.0 does not warm up and calibrate the isokinetic apparatus daily. Investigations with definite weights showed that the values for peak torque are 40-50 m higher when using the Iso-Kin 4.0 software in comparison to the original CYBEX software. Furthermore there are a lot of other parameters such as acceleration of the body, psychological alterations, pain, motivation, learning effects, and artificial oscillations of the registered curve, which can affect the results even when using the original CYBEX software. PMID- 7887009 TI - [Linear scleroderma. Report of 2 cases with a review of the disease entity]. AB - We report on two patients with linear scleroderma (a form of localised scleroderma) and their orthopaedic problems such as shortening of the limbs and contractions of the joints. The disease is very rare but easy to diagnose by its typical lesions of the skin (band like lesions with ivory like induration and hyper- or hypopigmentation; a peripheral erythema appears as a lilac ring). In the orthopedic management it is very important to follow the patient carefully during the period of growth for good planning of the conservative (physiotherapy and orthosis) and operative therapy, which in one of our patients consisted in repeated corrections as partial arthrodesis of the foot and osteotomies of the leg. PMID- 7887010 TI - Democratic governments and vaccines. PMID- 7887011 TI - Putting prevention research at risk: implementation of the Vaccines for Children programme. AB - The United States Department of Health and Human Services is in the process of implementing the recently created Vaccines for Children programme (VFC) that provides for expanded government purchase of childhood vaccines at capped prices. Vaccine companies have traditionally sold their vaccines to the government at discounted prices and to private providers at higher prices, and policymakers have encouraged this ad hoc cost-shifting system. Greatly increased government purchase of vaccines at artificially low capped prices will not have a significant impact on immunization rates, and, because vaccine manufacturers depend on private sector sales to finance research and development, such purchase will delay or curtail efforts to bring new vaccines to the market. PMID- 7887012 TI - Towards rabies elimination in Belgium by fox vaccination using a vaccinia-rabies glycoprotein recombinant virus. AB - Oral immunization of foxes by distributing vaccine baits was experimentally assessed and subsequently employed in the whole of the infected area of Belgium (10,000 km2). A vaccinia-rabies glycoprotein recombinant virus (VR-G) was used as vaccine because of its efficacy, safety and heat stability. Five 'full' campaigns of fox vaccination, carried out from 1989 until 1991, induced a drastic decrease in the incidence of rabies. The disease has disappeared from the major part of the initial infected area. In 1992 and 1993, three 'defence' campaigns, carried out along international borders, completely eliminated rabies virus infection from the fox population in 1993. PMID- 7887013 TI - Immunogenicity of the Escherichia coli fimbrial antigen K99 when expressed by Salmonella enteritidis 11RX. AB - Salmonella strains expressing the Escherichia coli fimbrial protein K99 were used to immunize adult mice, and the resulting anti-K99 T-cell responses were examined. Immunized animals displayed delayed-type hypersensitivity responses when challenged with K99 in the footpad. Lymphoid cells from immunized animals proliferated and released cytokines when cultured in vitro with K99 or peptides generated by cyanogen bromide treatment; the T cells which responded had the CD4+ phenotype. PMID- 7887014 TI - Should British soldiers be vaccinated against hepatitis A? An economic analysis. AB - We conducted a study to analyse the efficiency of introducing vaccination against hepatitis A to the schedule for troops in the British Army. The study design included a cost-effectiveness analysis (CEA) of cost per case avoided comparing active and passive immunization and a cost-benefit analysis (CBA). The study population comprised all British Army personnel as well as those soldiers assumed to be deployed to high-risk areas a variable number of times in 5 years. The average cost of one case of hepatitis A avoided by vaccination was calculated and compared with the average cost of achieving the same outcome by passive immunization. In a 5-year four-exposure scenario at a low incidence and using a 3% discount rate, avoiding one case of hepatitis A by vaccination would cost 52,865 pounds, against 97,305 pounds by passive immunization. The equivalent cost benefit ratios are 13.4 for gammaglobulin and 7.2 for vaccine. For fewer exposures the break-even point for vaccine is two exposures in 4 years. Although our estimates are sensitive to direct costs and relatively sensitive to the estimated incidence, vaccinating troops against hepatitis A appears to be a more efficient procedure than passive immunization, especially as a long-term investment in troops likely to effect several operational deployments. Given the difficulty of forecasting which troops would deploy, the best-buy strategy may be vaccination of troops most likely to deploy repeatedly. PMID- 7887015 TI - Comparative efficacy of biodegradable liposomes and microspheres as carriers for delivery of Vibrio cholerae antigens in the intestine. AB - The effect of the encapsulated antigens of Vibrio cholerae and their route of administration in induction of immune response was studied in experimental cholera. The antigenic proteins of V. cholerae El Tor strain KB207 were obtained by fractionation of cell-free lysate by high-performance liquid chromatography. The antigenic proteins were pooled and encapsulated in biodegradable liposomes and poly(D,L) lactic co-glycolic acid microspheres. Rabbits were immunized with free as well as encapsulated antigens by different routes. Liposome-encapsulated antigens delivered intraintestinally offered maximum protection. Orally or intraintestinally delivered antigens in microspheres failed to elicit a significant immune response, although as a carrier microspheres were comparable to liposomes when judged by the subcutaneous route. The results suggested that liposomes and microspheres could be used as carriers of protective antigens of V. cholerae for effective immunization. PMID- 7887016 TI - Congenital toxoplasmosis in the Balb/c mouse: prevention of vertical disease transmission and fetal death by vaccination. AB - Vertical disease transmission only occurs in Balb/c mice infected with Toxoplasma gondii for the first time during pregnancy. This is similar to the situation in humans, where a previous infection with T. gondii tends to give life-long immunity against reinfection and fetal disease transmission. The Balb/c mouse therefore provides a suitable model to study the effectiveness of T. gondii vaccine candidates. A soluble tachyzoite antigen (STAg) preparation was used to vaccinate female Balb/c mice. STAg was inoculated subcutaneously into Balb/c mice in phosphate-buffered saline (PBS), emulsified in Freund's complete adjuvant (FCA), or entrapped within non-ionic surfactant vesicles (NISV). While all inocula induced cellular immunity as measured by parasite-specific spleen cell proliferation in vitro, the highest mean proliferative values were observed in spleens from mice where NISV had been used as the adjuvant and the lowest values were observed where FCA had been used. More importantly, cultures from the NISV/STAg vaccinated mice produced significantly more gamma-interferon than the other experimental groups. This vaccine formulation was therefore identified as that most likely to induce protective immunity against toxoplasmosis. Mice were inoculated subcutaneously with either NISV/STAg or STAg in PBS 4 and 2 weeks before mating and infected orally with 20 tissue cysts of T. gondii on day 12 of pregnancy. The incidence of fetal infection and death in these mice and non vaccinated infected dams was compared. Of 84 pups born to 14 non-vaccinated dams 45 were viable, of which 18 were found to be infected on reaching maturity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887017 TI - Bacillus anthracis protective antigen, expressed in Salmonella typhimurium SL 3261, affords protection against anthrax spore challenge. AB - The protective antigen (PA) gene from Bacillus anthracis has been expressed in Salmonella typhimurium SL 3261 (aroA). Expression was achieved by cloning the gene after the plac promoter in a high copy number plasmid. The recombinant PA was exported into the periplasm. This construct was unstable in vivo and also reduced the colonization ability of the host S. typhimurium. Mouse-passaging of the recombinant Salmonella resulted in a strain with enhanced colonization ability and increased stability of the plasmid in vivo. This effect appeared to be due to a reduction in copy number of the PA-encoding plasmid. Mice were vaccinated with recombinant S. typhimurium and adjuvanted PA and challenged with virulent B. anthracis. Only mice vaccinated with adjuvanted PA or orally with the mouse-passaged recombinant showed partial protection. The degree of protection observed after oral vaccination with the recombinant S. typhimurium was similar to the degree of protection afforded by adjuvanted PA and suggested that the use of S. typhimurium to deliver PA is an effective approach for inducing protection against B. anthracis. The results presented also suggest that the degree of protection demonstrated in the mouse may not fully indicate the potential of the recombinant Salmonella as an effective vaccine in other species. PMID- 7887018 TI - Immune response in healthy volunteers vaccinated with BCG plus killed leishmanial promastigotes: antibody responses to mycobacterial and leishmanial antigens. AB - Antibody (IgG) responses to mycobacterial (BCG; PPD; Mycobacterium leprae soluble antigen, MLSA) and leishmanial (Leishmania mexicana LV4) antigens were measured in 208 initially PPD and leishmanin skin-test negative volunteers divided into four vaccine groups as follows: 68 received BCG plus killed promastigotes (group A), 47 received BCG alone (group B), 47 received killed promastigotes alone (group C), and 46 formed the diluent control (placebo, group D). Three vaccine doses were administered at 8-12 week intervals. Vaccinees were bled immediately prior to each vaccination, and again at 3- and 12-month follow-up. Skin tests were performed prevaccination, and again at the 3- and 12-month follow-up. Anti BCG, anti-PPD and anti-MLSA IgG levels increased significantly in groups A and B receiving BCG. The presence of leishmanial antigen (with BCG) in the inoculum suppressed the IgG response to Mycobacterium tuberculosis/Mycobacterium bovis related (PPD and BCG), but not M. leprae-related (MLSA)-related, antigens. A small but significant increase (relative to prevaccination level) in response to MLSA, but not to BCG or PPD was observed in the non-BCG-vaccinated groups. The background level of response to mycobacterial and leishmanial antigens was higher in the Venezuelan vaccinees than in non-endemic (British) volunteers. Responses to leishmanial antigen were not enhanced in the two vaccine groups receiving killed promastigotes (with/without BCG) compared with the BCG alone and placebo groups. Instead, all vaccine groups showed a pattern of response consistent with either (i) a response to the skin-test antigen or, more likely, (ii) seasonal endemic exposure to leishmanial antigen. Interestingly, this endemic response to leishmanial antigen was enhanced in the vaccine groups receiving BCG, despite the fact that group B received no leishmanial antigen in the vaccine inoculum. When prevaccination IgG levels (mean + 3 standard deviations) were used to determine a negative cut-off, a low percentage (< 38%) of vaccinees converted to responder status for either anti-mycobacterial or anti-leishmanial responses, and those who did would be classified as 'low-responder' status compared with titres observed in severe forms of disease. Hence, although there was evidence for a background endemic response to both leishmanial and mycobacterial antigens, there was no evidence that vaccination per se led to a potentially disease exacerbatory level of TH2-associated antibody response especially with respect to the anti leishmanial response.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7887019 TI - Stabilization and enhancement of interleukin-2 in vitro bioactivity by new carriers: supramolecular biovectors. AB - Human recombinant interleukin-2 can be associated and released from supramolecular biovectors (SMBVs), consisting of particles made of polymerized polysaccharides. The particles are substituted with phosphate residues and contain bound lipid molecules (palmitic acid) buried near their surfaces. The association of IL-2 with SMBVs modifies its in vitro bioactivity. SMBVs prolong the growth of IL-2-dependent cells, enhance IL-2 proliferative activity and restore the activity of impaired IL-2. These properties mainly depend on the presence of lipids linked to the SMBV and on both the degree of acylation and the SMBV: IL-2 ratio. SMBVs are therefore good candidates for the stabilization and enhancement of the biological activity of IL-2. PMID- 7887020 TI - Adjuvant Quil A improves protection in mice and enhances opsonic capacity of antisera induced by pneumococcal polysaccharide conjugate vaccines. AB - The adjuvant effect of Quil A on the primary antibody response of mice to pneumococcal capsular polysaccharide conjugates was examined. Quil A increased the anti-capsular polysaccharide antibody titres, the protection against Streptococcus pneumoniae, and the opsonic capacity of the antibodies as measured in a newly developed in vitro phagocytosis assay, using the mouse macrophage cell line J774. PMID- 7887021 TI - Human immunization in developing countries: practical and theoretical problems and prospects. AB - While measles, pertussis and tetanus were responsible during the early 1990s for nearly two million deaths in developing countries, no deaths were attributable to them in industrialized countries. More than 96% of global deaths by communicable diseases were also from developing countries. Respiratory infections ranked first in communicable morbidity at all ages. Even though vaccines of bacterial or viral origin or a prophylactic for passive immunization are produced in 24, 16 and 15 developing countries, respectively, none of the developing countries manufactures a plasma-derived prophylactic or biological response modifier. Nearly every country relies on import of one or more vaccines. The suboptimal performance of otherwise meritorious products has been due to faulty vaccine administration practices. Expanding populations, poverty and lack of education, cold-chain defects, and inadequate facilities for transport of vaccines to target populations in remote areas have been responsible for the poor performance of vaccines in the community. Mounting foreign debts and budgetary strains resulting from the care and prevention of AIDS/HIV have considerably strained national and international efforts to offer routine vaccinations in childhood and pregnancy. This dismal situation could be tackled through research to obtain environmentally stable products for prophylactic use and monoclonal antibody formulations for passive immunization, and through international financial and technical support. All countries should exercise some technical control of the quality of imported and indigenous vaccines during their use for curative or prophylactic purposes. The involvement of private clinicians in immunizations would strengthen national efforts for control of communicable diseases including AIDS, but this is not enough if the local factors cited above are not improved. PMID- 7887022 TI - Safety and immunogenicity of the oral E. coli K12-S. flexneri 2a vaccine (EcSf2a 2) among Israeli soldiers. AB - A double-blind placebo-controlled study was carried out on the safety and immunogenicity of the oral Shigella flexneri (EcSf2a-2) vaccine among Israeli soldiers. Sixty volunteers received the vaccine and 59 received placebo. Fifty three were given the full vaccine regimen (four doses). Doses ranged between 4.1 x 10(8) and 1.1 x 10(9) c.f.u. Visits to the unit clinic for mild gastrointestinal symptoms were common after the first dose in vaccinees (13%) as compared with placebo recipients (5%), but the difference was not significant, p = 0.12. Similarly, there was no difference between the groups for either gastrointestinal or non-gastrointestinal complaints reported by questionnaire. The vaccine strain was excreted by 69% and 67% of the vaccinees one day after receiving the second and the fourth doses, respectively. As judged by antibiotic susceptibility, phage typing and restriction fragment length polymorphism (RFLP), the vaccine strain emerged as genetically stable after replication in human gut and shedding. There was neither bacteriological nor serological evidence of transmission of the vaccine from vaccinees to placebo recipients. Eighteen of 26 (69.2%) and 11 of 30 (36.7%) vaccinees had significant IgA secreting cell responses 7 and 21 days after the first dose, respectively. Significant IgA or IgG serum antibody response to S. flexneri 2a LPS was detected in 30% of the vaccinees. These results support further evaluation of EcSf2a-2 vaccine protective efficacy in field studies. PMID- 7887023 TI - Protection of rhesus macaques from SIV infection by immunization with different experimental SIV vaccines. AB - The immunogenicity and efficacy of an inactivated whole SIVmac (32H) preparation adjuvanted with muramyl dipeptide (SIV-MDP) and a gp120-enriched SIVmac (32H) ISCOM preparation (SIV-ISCOM), were compared by immunizing four rhesus macaques (Macaca mulatta) four times with SIV-MDP and four others in the same way with SIV ISCOM. Two monkeys immunized with whole inactivated measles virus (MV) adjuvanted with MDP (MV-MDP) and two monkeys immunized with MV-ISCOM served as controls. In the SIV-ISCOM-immunized monkeys higher SIV-specific serum antibody titres were found than in the SIV-MDP-immunized monkeys. In contrast to the MV-immunized monkeys all SIV-MDP- and SIV-ISCOM-immunized monkeys were protected against intravenous challenge 2 weeks after the last immunization with 10 median monkey infectious doses (MID50) of a cell-free SIVmac (32H) challenge stock propagated in the human T-cell line C8166. After 43 weeks the protected monkeys were reboosted and 2 weeks later rechallenged with 10 MID50 of the same virus produced in peripheral blood mononuclear cells (PBMC) from a rhesus macaque. None of these animals proved to be protected against this challenge. In a parallel experiment in which the same numbers of monkeys were immunized in the same way, the animals were challenged intravenously with 10 MID50 of PBMC from an SIVmac (32H)-infected rhesus macaque. Two out of four SIV-MDP- and two out of four SIV-ISCOM-immunized monkeys proved to be protected from SIV infection. PMID- 7887024 TI - Interaction of Haemophilus influenzae type b conjugate vaccines with diphtheria tetanus-pertussis vaccine in control tests. AB - The effects of combining three Haemophilus influenzae type b (Hib) capsular polysaccharide vaccines, conjugated to different proteins, with DTP vaccine on the subsequent control testing were examined. The addition of the Hib vaccines had little effect on the reactogenicity or the potency of the whole-cell pertussis component. The potency of, and antibody responses to, the diphtheria component were also unaffected in all three combinations. However, combination with the Hib vaccine comprising polysaccharide conjugated to tetanus toxoid resulted in a fivefold potentiation of the tetanus potency and large increases in the antibody responses to tetanus toxin and toxoid and Hib polysaccharide. These results have implications for the control testing of combined vaccines containing a whole-cell pertussis component and Hib polysaccharide-tetanus protein conjugate vaccine. PMID- 7887025 TI - A type-specific avian influenza virus subunit vaccine for turkeys: induction of protective immunity to challenge infection. AB - The fraction NP/HA (nucleoprotein/haemagglutinin) obtained from n-octyl-beta-D glucopyranoside-treated influenza A H5N2 virus was highly enriched for NP with residual haemagglutinin. This preparation was incorporated in ISCOMs. This potent 'immunostimulating complex' induced the production of high antibody titres in turkeys. The NP/HA ISCOMs preparation was found to protect turkeys from both homologous and heterologous challenge infection as shown by reduced viral titres in the lung and trachea of vaccinated turkeys. Clearance of the virus from trachea and lungs was seen at late stages of infection. The vaccine also induced a cellular immune response as measured by T-cell proliferation and a delayed-type hypersensitivity response. The results reported in this study demonstrate that the NP/HA ISCOM vaccine is capable of inducing type-specific immunity and that it has potential utility as a vaccine in turkeys. PMID- 7887027 TI - Adverse reactions to purified chick embryo cell rabies vaccine. PMID- 7887026 TI - Effective induction of neutralizing antibodies with the amino terminus of VP2 of canine parvovirus as a synthetic peptide. AB - Fourteen synthetic peptides corresponding to previously mapped antigenic sites in VP2 of canine parvovirus (CPV) were used for immunization of rabbits to identify antiviral properties favourable for inclusion into a vaccine. Most antipeptide antisera obtained were reactive with viral protein, and with one of them it was possible to locate the hypothetical amino terminus of VP3 within positions 15-31 of VP2. Virus-neutralizing antibodies were only obtained with two overlapping 15 mer peptides corresponding in sequence to the amino terminus of VP2 (MSDGAVQPDGGQPAVRNERAT). Antibodies in the neutralizing sera bound most strongly to amino acids of the sequence DGGQPAV within the N-terminus of VP2, indicating that efforts to develop a synthetic vaccine against CVP should be focused on this stretch of amino acids. The two peptides induced long-lasting immunity (at least 8 months) using either Freund's adjuvant or aluminium hydroxide plus Quil A. Thus, this approach delineated the exact peptide sequence useful for vaccines applied to the amino-terminal region of VP2. These findings in experimental animals form a solid basis for exploration of a synthetic peptide vaccine against parvovirus infection in dogs, minks or cats. PMID- 7887028 TI - Influenza vaccine and dermatomyositis. PMID- 7887029 TI - Diagnosis of varicella-zoster and evaluation of varicella vaccine by passive haemagglutination by non-invasive procedures. PMID- 7887030 TI - An unlikely Mycoplasma pulmonis vaccine candidate. PMID- 7887032 TI - [Specific in situ labeling of apoptosis shows different rates of programmed cell death in non-Hodgkin lymphomas]. AB - Two new techniques were used to quantify cell death (i.e. DNA fragmentation) in situ: (1) 3' overhangs of the fragmented DNA were end labelled with biotin-7-dATP and TdT (peroxidase/DAB). (2) In situ nick translation (ISNT) was performed with DNA polymerase 1 and biotin-7-dATP, to label single strand segments of DNA (peroxidase/DAB). Both methods were tested to be negative in ischemic and tumor necrosis, and negative for mitotic figures. In 26 centroblastic Non Hodgkin lymphomas (CB) (monomorphous subtype [n = 9], polymorphous subtype [n = 7], secondary [n = 10]), 14 chronic lymphocytic leukemias and two immunocytomas these methods were employed to quantify the rate of cell death. ISNT proved to be more sensitive than end labelling. By ISNT, CB had a mean cell death rate of 250/10HPF (monomorphous type: 429/10HPF, polymorphous type: 222/10HPF, secondary: 111/10HPF). CLL showed a significantly lower rate (28/10HPF). These data suggest, that the low rate of cell turnover in CLL is indicated by a low rate of cell proliferation and a low rate of programmed cell death. In CB the high proliferation rate was accompanied by a high level of cell death. In CB/monomorphous a high turnover state with a very high proliferation and cell death rate was found, whereas CB/polymorphous represents an expansive state as indicated by a lower rate of cell death. CB/secondary showed almost no programmed cell death and therefore was interpreted as a high expansive state neoplasia. PMID- 7887031 TI - [Murine leukemia virus Akv promotes bone tumor development in fos-transgenic mice]. AB - Newborn hMT-fos-LTR transgenic C3H mice and their non-transgenic siblings were infected with Akv, derived from the ecotropic provirus of the AKR mouse. Bone sarcomas in non-infected transgenics were observed in 20% (3/15) of females at 448 +/- 25 days and in 8% (1/12) of males at 523 days. Akv-infected transgenics developed bone tumors with higher frequency and at younger age: Females in 69% (20/28) at 268 +/- 122 days, males in 83% (24/29) at 279 +/- 109 days. In the majority of the bone tumors of Akv-infected transgenics (70% in females, 59% in males) cellular atypia was lacking and the histological pattern resembled human parosteal osteosarcoma. Only 50% (12/24) of bone tumors in Akv-infected transgenics revealed newly integrated virus sequences by Southern analysis. PCR analysis detected Akv sequences in DNAs of all tumors. Obviously, the insertion of Akv in a few cells induced the considerably accelerated bone tumor growth. PMID- 7887033 TI - [Patient-controlled analgesia in treatment of postoperative pain]. AB - Patient-controlled analgesia (PCA) is a newer technique for pain management. Patients are allowed to self-administer small analgesic bolus doses, which have been preprogrammed by the physician, into a running intravenous infusion, intramuscularly, subcutaneously or even into the epidural space. Patients' demands are mostly controlled by computer-driven infusion pumps, but can also be delivered by simple disposable devices. Lockout times, concomitant infusions and hourly maximum doses can be set in most PCA pumps. Clinical experience with PCA demonstrates that individual variability in pain sensitivity and analgesic needs are of utmost importance. In contrast to earlier expectations, PCA opiate consumption is usually higher than with restrictive conventional dosing regimes, but without an increase of serious side effects. Such results let assume that many patients under conventional i.m. techniques must be considered to be underdosed. Patients acceptance is generally enthusiastic for self-control. It is suggested that PCA results should be used for the improvement of conventional techniques. PCA has also been found valuable for scientific pain studies, e.g. to determine predictors of postoperative pain, drug interactions and pharmacokinetic experiments. This review concentrates on intravenous PCA during the early postoperative period. PMID- 7887034 TI - [Transcutaneous po2 measurement in follow-up of severe soft tissue injuries of open fractures]. AB - The transcutaneous assessment of tissue oxygenation has become an useful method in evaluating microcirculatory disorders in different diseases. In this clinical experimental pilot study the impact of compound fractures on tissue oxygenation was examined. Using a special probe placed directly into the muscle, tissue oxygenation was measured at the site of tissue injury as well as at one non injured site within the same fractured extremity. Furthermore, also one non injured extremity was measured as a control. At the injured site tissue oxygenation was significantly increased during the first 4 days after trauma as compared to the non-injured extremity (40.7 +/- 1.8 mmHg vs. 23.5 +/- 4.1 mmHg). At the same time the non-injured site of the fractured extremity appeared to be significantly less oxygenated as compared to the noninjured extremity (13.2 +/- 2.3 mmHg vs. 23.5 +/- 4.1 mmHg). After day 4 until the end of the study (day 10) a complete return to normal values was noted at both sites. In conclusion it is most likely that due to a change of microcirculation within the fractured extremity the injured site is temporarily oversaturated by oxygen combined with lacking oxygenation at the non-injured site. As the microcirculatory status may be important in making decision in trauma surgery (e.g. whether or not to amputate) the method of transcutaneous oxygen measurement is a practical and useful method in trauma care. PMID- 7887035 TI - [Closed tibial fracture--reamed or unreamed intramedullary nailing. A clinical study]. AB - When comparing the unreamed tibial nail (UTN) with the external fixator in the treatment of open tibial fractures the UTN has shown advantages. Whether we can find these advantages also in the treatment of closed tibial fractures using the UTN instead of a reamed system should be clarified in the following study. We compared 35 UTN treated patients with 35 patients that were treated with a reamed A0-universal tibial nail. Both groups showed no differences in age, sex, etiology and severity of trauma. The fractures were classified by the A0-classification of fractures and the soft tissue damage by the classification of Tscherne and Oestern. The length of mean hospital stay, the time of partial weight bearing and the duration of fracture healing, were shorter using the UTN. 5 of 9 complications using the UTN were immanent to the system (deformation of the locking screws). The other complications were 2 axis shifts, 1 compartment syndrome and 1 pseudarthrosis. The other group showed 1 hematoma, 1 axis shift, 1 compartment syndrome, 2 thromboembolic complications, 2 infections and 3 cases of pseudarthrosis. We think that there is an advantage to use an UTN instead of a reamed nailing system in treatment of closed tibial fractures. PMID- 7887036 TI - [Secondary plate osteosynthesis of open fractures of the lower extremity--still a therapeutic alternative!?]. AB - During the time period from May 1, 1990 to July 31, 1993, a total of 102 tibial and 144 femur fractures were treated in the Department of Traumatology of the University of Bonn. 45 patients with 25 open tibial and 22 open femur fractures were treated according to a regimen including primary stabilization, usually in an external fixator, soft tissue reconstruction and delayed open reduction and internal fixation using an A0-plate. A majority of the patients were involved in motor vehicle accidents, leading to multiple injuries in 26 instances. The complication rate of 17% is comparable to the reports following intramedullary stabilization. Only three chronic infections, following one grade two open femur fracture, one grade two and one grade three open tibial fracture, were seen. Bony union was achieved after 24 weeks. It is shown that the use of the A0-plate in the treatment of open fractures of the femur and tibia offers not only logistic advantages but represents a viable alternative for the delayed stabilization of these injuries. PMID- 7887037 TI - [May recurrent goiter be resected bilaterally? Value and results of intraoperative laryngoscopy]. AB - Operations for recurrent goiter are considered to range among the most difficult procedures in thyroid surgery and are marked by unusually high subsequent damages of the recurrent nerve. Results from 89 patients with recurrent goiter operated over the last six years and our own experiences with intraoperative laryngoscopy are presented. This procedure is applicable in 60% of all cases with true bilateral thyroid recurrency and accounts for a realistic help in deciding whether to continue the operation with simultaneous resection of the contralateral side. PMID- 7887038 TI - [Simultaneous interventions of the thyroid gland in primary hyperparathyroidism (pHPT)]. AB - Among 334 neck explorations for primary hyperparathyroidism (pHPT) between 1979 and 1993 120 (33.9%) thyroid operations were performed simultaneously. Histologic examination revealed 40 thyroid adenomas, 43 nodular goiters, 8 thyroiditis and 9 differentiated carcinomas. In 20 cases the indication was doubtful retrospectively, as evaluated by postoperative histology. Of the 9 carcinomas there were 4 small papillary, 3 papillary pT2 No Mo and 2 follicular pT2 No Mo. Perioperative morbidity of the simultaneous operations was not significantly increased compared to the parathyroid exploration alone. We conclude, that pre- and intraoperative thyroid examination should be performed in pHPT and decision for a simultaneous operation should be made generously. PMID- 7887039 TI - [Disposable versus reusable instruments in laparoscopic surgery--a controlled study]. AB - The instruments for laparoscopic surgery are usually available in a disposable and in a reusable type. We performed a prospective, randomized study, based on the most frequent laparoscopic operation, the cholecystectomy, in order to directly quantify and compare the advantages and disadvantages of both types of instruments. 158 patients, who planned to undergo a cholecystectomy, were randomly distributed into two groups. 80 patients (group A) underwent surgery with reusable instruments and 78 patients (group B) with disposable instruments. We investigated the following parameters and compared them for both groups: length of operation, complications, conversion rate to open surgery, subjective postoperative pain, length of inability to work, technical problems during operation, postoperative hospitalization time, satisfaction of operating room personnel. The analysis of the results demonstrates no difference in the postoperative hospitalization time, in the postoperative complication rate, subjective pain sensation and postoperative inability to work. Differences in favour for the group of patients, operated with disposable instruments, were found in the conversion rate, in the length of operation and, statistically significant, in the amount of intraoperative problems, caused by instrument technical reasons. Even if considering the greater expenses in time and personnel costs, operations with reusable instruments are in average 1015 DM cheaper. PMID- 7887040 TI - [Dorsal retroperitoneoscopic adrenalectomy--a new surgical technique]. AB - For the first time the surgical technique of right and left adrenalectomy by a posterior percutaneous retroperitoneoscopic access is described. The adrenal gland is mobilized after creation of a pneumoretroperitoneum and insertion of 3-4 trocars beneath the 12th rip. Indications for this new method are small, benign adrenal tumours or adrenocortical hyperplasias. By this method, the potential advantages of a posterior approach and minimally-invasive surgery are combined. This surgical technique might become a major advancement in adrenal surgery. PMID- 7887041 TI - [Diagnostic and therapeutic problems of acute lower gastrointestinal hemorrhage]. AB - In a four year period (1990-93) 75 patients were treated in our hospital for acute lower gastrointestinal bleeding. In the course of diagnostic procedures an upper gastrointestinal bleeding was excluded routinely and further 126 endoscopic measures were performed. All patients underwent rectoscopy and additional partial or total coloscopy. In addition to that, 16 scintigrams and 7 angiograms were taken. The validity of the endoscopic measures was 0.73, scintigraphy and angiography were less valid with 0.53 and 0.34. Therefore endoscopic diagnostic procedures are of more value. 32 of these 75 patients underwent operative treatment. Recurrent bleeding after operative treatment was seen in 6.25%. Overall mortality was 5.33%. Because prognosis of a recurrent bleeding after operative treatment is poor, primary subtotal colectomy is indicated when the source of bleeding can not be localized. PMID- 7887042 TI - [Endosonography of the anal canal in traumatic incontinence]. AB - We performed transanal endosonography in 6 patients with severe faecal incontinence suspicious of traumatic origin. Traumatic lesions of the anal muscles could be localized precisely or excluded. Surgical procedures were chosen according to the sonographic picture. PMID- 7887043 TI - [Leiomyosarcoma of the rectum]. AB - The distinction between leiomyoma and high differentiated leiomyosarcoma can be difficult. The most important distinguishing feature is the number of mitoses. Additionally the tightness of the cells, the number of necroses and cell atypias and the size of the tumor are significant. The most common therapy for large and low differentiated leiomyosarcomas of the rectum are the abdomino-perineal resection or the low anterior resection. In high graded tumors of less than 2.5 cm the radicality of the surgical treatment is questioned. Some authors recommend a wide local excision, but in this case a high local recurrence rate has to be expected. This is the reason for a more radical treatment of all leiomyosarcomas of the rectum. Chemotherapy and radiotherapy are generally not effective. The prognosis is poor. PMID- 7887044 TI - [Bouveret syndrome--a rare form of pyloric obstruction]. AB - Gallstone ileus represents a severe complication of cholelithiasis. The incidence of serious disease concomitant with gallstone ileus is high; it is most often seen in elderly patients and contributes to its high morbidity and mortality rates. Bouveret's syndrome is a rare form of gallstone ileus, characterized by its duodenal site after migration through a cholecysto-duodenal fistula in almost all cases. We report on a patient with Bouveret's syndrome. The etiology, pathogenesis, diagnosis and therapeutic approach with literature review are presented and discussed. PMID- 7887045 TI - [Patient expectations from lumbar intervertebral disk operations-- an analysis of a questionnaire survey of 200 patients]. AB - Using a questionnaire 200 patients with lumbar disc herniation syndrome were asked preoperatively about important aspects of care during their hospitalisation. They had to answer 17 questions using a classification system of 7 points. The most important point for patients was the qualification of the head of the clinic, followed by a distinct explanation about risks during operation. Aspects of discharge from clinic, recovery in fitness for work or the extent of the scar were of minor interest. PMID- 7887046 TI - [The "Neuropsychological Screening Test (NST)": initial validation and reliability studies]. AB - Medical examinations only insufficiently measure cognitive impairment in neurological and neurosurgical patients. Due to costs an personnel shortages, adequate neuropsychological test methods are typically bypassed. Indeed, the very size and methodological problems of current tests impede their application in clinical practice. To resolve this dissatisfying state of affairs, we have developed a standardized, scored form of initial neuropsychological examination. The Neuropsychological Screening Test (NST) comprises 45 items, is easy to handle, and can be conducted in 15-20 min. The NST measures psychic performance along functional parameters such as orientation in place and time, primary and secondary language, visuospatial ability, attention, and memory skills. We have assessed the validity and reliability of the NST in a prospective study. 129 neurosurgical patients (60% malignant or benign cerebral tumors, 21% vascular malformations with and without subarachnoid hemorrhage, 6% traumatic brain injury, 3% hydrocephalus, 10% others) and 52 control subjects were included in the study. The difference in average total NST-scores was highly significant for the two groups (t = -7.84, DF = 177.93, p < .001). In addition, two chronologically separate subsamples of NCH patients (N = 81) and controls (N = 35) were tested using the Mini-Mental State (MMS). The correlation between total NST-score and MMS results was r = .49 (p < .001). Cross-tabulation was used to set a cut-off score, by means of which 80% of the neurosurgical patients were identified as true positive and 74% of the controls as true negative. A 24-hour retest confirmed the NST as reliable to .85 (p < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887047 TI - [Are sacroiliac joint block and insertion tendinosis of the musculus erector trunici too rarely diagnosis as the etiology of failed back syndrome after intervertebral disk operation]. AB - Dysfunction of sacroiliac joint and tendinosis of erector trunci muscle may cause severe pain after lumbar discectomy. In this paper we discuss pathophysiology, clinical appearance as well as specific diagnostic procedures and therapy. We want to point out that sacroiliac joint dysfunction must be taken into consideration if persistent pain occurs after discectomy. PMID- 7887048 TI - [Why still use myelography in neurosurgery?]. AB - Recently CT scan and NMR imaging have become diagnostic routine methods for spine lesions, while myelography is no longer the method of choice in most cases. From the experience of our clinic, however, there remain some neurosurgical indications, which will be the contents of this publication. We would like to give a review of the present literature. Still remaining indications are: 1. Traumatic nerve root lesions 2. Anomalies of lumbosacral nerve roots 3. Cervical disc herniation: anterior disc excision vs. posterior operation. 4. Stenosis of the spinal canal in more than 2 levels 5. Neurological deficit after trauma of the spine 6. Functional Myelography 7. Spinal arteriovenous malformations 3 Patients are presented in the crucial phase of diagnostic evaluation. Based on their outcome, the indications of myelography are discussed. PMID- 7887049 TI - [Emergency drainage of acute intracranial hematomas with unsterile conditions during computerized tomography]. AB - From January 1979 to December 1993, we treated 761 patients with epidural (n = 184) or subdural (n = 577) haematomas. Twenty-six were subjected to emergency trepanation on the CT-table, since their condition was considered life threatening. All fulfilled the following criteria: 1. Glasgow Coma Score below 9, 2. Progressive coma and/or progressive anisocoria and/or 3. Other signs of acute life risk correlating with an intracranial haematoma. Nine of these 26 patients died (3 out of a total of 17 with epidural and 6 out of a total of 9 subdural haematomas). In 5 cases the cause of death was brainedema, in 3 cases a multiorgan failure, and one pneumonia. None of the patients acquired an infection at the trepanationsite or elsewhere within the CNS. Twelve patients had postoperative complications (8 with epidural and 4 with subdural haematoma). These caused a prolongation of the average hospitalization period. Patients with uncomplicated follow-up were discharged after 17.6 +/- 4.2 days, as opposed to 44.8 +/- 15.7 days for complicated cases. Six months following discharge 8 of 17 patients with an epidural haematoma had reached stage 5 of the Glasgow Outcome Scale, 4 were in stage 4, 1 in stage 3, and 1 in stage 2. Three patients had died. None of the 9 patients with a subdural haematoma had reached stage 5. One patient had reached stage 4, 2 stage 2, while 6 patients had died. PMID- 7887050 TI - [Stereolithography as a new method of reconstructive surgical planning in complex osseous defects of the cranial base. Technical note]. PMID- 7887051 TI - [A case of diastematomyelia (split cord malformation type I) with clinical manifestation in adulthood]. AB - We present the case of a female patient with split-cord malformation type I (diastematomyelia) who developed first symptoms as an adult and worsened markedly after intramedullary injection of local anaesthetics. Our own observations are compared with the small number of cases known from the literature. We are using the morphological and clinical classification of spinal malformations of Pang et al. (1992), which is based on a uniform disturbed embryonal development [18, 19]. The 52-year-old patient presented to her family physician in September 1991 with pain in the region of the vertebral column which had developed gradually over a period of two weeks. Following unsuccessful analgetic and muscle-relaxing therapy, the family physician had the patient transferred to the orthopedic department of a hospital. Lumbar peridural infiltrations were carried out there in February 1992 for a suspected disc prolapse. Since June 1992, she had no longer been able to walk. In addition, there had also been a progredient urinary incontinence since April 1992. The spinal CT scan reveals a duplication of spinal cord starting at the level of L4 as well as a bony spur dividing the spinal cord at levels L4 and L5. MRI of the vertebral column likewise reveals a duplication of the spinal cord starting at L4 as well as a low conus and a bone spur extending from L4 to L5 is also visualized here. Each primordial spinal cord is surrounded by its own dura mater. Altogether, this led to the diagnosis of split cord malformation type I according to Pang et al. [18].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887052 TI - Barrels VI: proceedings of a satellite symposium of the 1993 Society for Neuroscience meeting. PMID- 7887053 TI - Semi-serial electron-micrographic reconstruction of putative transducer sites in Pacinian corpuscles. AB - The Pacinian corpuscle (PC) is composed of an afferent neurite surrounded by an accessory capsule formed by concentric layers of lamellae. Projecting from the neurite, which is elliptical in cross-section, are "filopodia" or axonal, spike like extensions. These filopodia are the putative sites of transduction. It has been proposed that two populations of filopodia organized in morphofunctional opposition exist, and that this arrangement is responsible for the bidirectional sensitivity of PCs as seen in receptor potential recordings. In order to explore this possibility, PCs obtained from cat mesentery were processed for electron microscopy, and semiserial reconstructions were made. We evaluated the extensions' (n > 110) locations, inclusions, shapes, and sizes. The filopodia were found to project along the major elliptical axis of the neurite, their density being approximately 2.8 per micron. The filopodia were found to contain filaments, vesicles, and amorphous ground substance, and dense accumulations of mitochondria were found at their bases. Measurements of their size (i.e., length, width, and height) suggest that there are two different types of filopodia. No other obvious relations among filopodial type, location along the neurite, and landmarks for transduction were found. The presence of the two filopodial types may be the basis for the bidirectional sensitivity of the PC. PMID- 7887054 TI - Effects of postnatal blockade of cortical activity with tetrodotoxin upon the development and plasticity of vibrissa-related patterns in the somatosensory cortex of hamsters. AB - Several previous studies have shown that postnatal blockade of thalamocortical activity with either tetrodotoxin (TTX) or the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovalerate (APV) does not prevent the formation of vibrissa-related patterns in the primary somatosensory cortex of rats. One limitation of these studies is that this pattern forms very shortly after birth in rats, and there may be only a very limited time over which it may be influenced by activity blockade. In the present study, the effect of activity blockade was evaluated in a more altricial rodent, the hamster. The present study showed that a pattern of thalamocortical afferents corresponding to the vibrissae is not observed until the fourth postnatal day in hamsters. Nevertheless, application of TTX-impregnated implants to the cortices of newborn hamsters had no qualitative or quantitative effect upon vibrissa-related patterns in the primary somatosensory cortices of these animals. Moreover, TTX implants did not prevent the changes in patterns that followed cauterization of a row of vibrissa follicles. PMID- 7887055 TI - Metabolic mapping of the forelimb motor system in the rat: local cerebral glucose utilization following execution of forelimb movements mainly involving proximal musculature. AB - The present study was undertaken to establish a metabolic map of forelimb motor pathways under conditions of physiological activation. For that purpose, we used the [14C]2-deoxy-D-glucose (2-DG) method to identify forebrain and midbrain centers showing an increase in 2-DG uptake in animals trained to execute specific lever-pressing movements with the right forelimb. Following repetitive execution of these movements, principally involving proximal (shoulder, elbow, and wrist) muscles, increases in 2-DG uptake were found contralaterally in several neocortical or subcortical centers. The largest left-right differences in local cerebral glucose utilization (LCGU) were found in a central region of the sensorimotor cortex composed of the caudal part of area 3 of the frontal cortex (Fr3; p < 0.01), the intermediate part of area 1 of Fr (Fr1; p < 0.01), and the forelimb cortical area (p < 0.04). Fr3 was the brain center with the highest differences in left-right LCGU. This central region of the sensorimotor cortex seems to correspond closely to the caudal forelimb area of Neafsey et al. (1986). Intermediate left-right differences in LCGU were found (1) in the just-adjoining rostral-medial areas of the motor cortex involving the intermediate part of area 2 of Fr (Fr2; p < 0.01) and the rostral part of Fr1 (p < 0.04), and (2) in the rostral part of area 1 of the parietal cortex (Par1; p < 0.01) and the caudal part of area 2 of Par (Par2; p < 0.05), both corresponding to forelimb representation. Weak (not statistically significant) left-right differences in LCGU were found in the rostral parts of Fr2 and Fr3, in the caudal parts of Fr2 and Fr1, in the hindlimb cortical area, and in the caudal part of Par1 and the rostral part of Par2. In the remaining cortical areas (cingulate; agranular and granular retrosplenial; temporal; and occipital), there was practically no difference in left-right 2-DG uptake. In addition, increased 2-DG uptake was present contralaterally in several subcortical motor-related centers. In those centers in which a somatomotor map has been established (caudate putamen, ventral lateral and ventral posterolateral thalamic nuclei, and red nucleus), increased 2 DG uptake was found in regions corresponding to forelimb representation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887057 TI - Heat-induced pain diminishes vibrotactile perception: a touch gate. AB - The gate control theory of pain (Melzack and Wall, 1965) suggests that tactile stimuli can decrease the perception of pain. We have found the reverse effect: Heat at levels that induce pain can substantially suppress tactile sensitivity, independently of shifts in attention or arousal. Ten human observers were stimulated by a tonic, pain-producing heat stimulus and vibrotactile stimuli (1, 10, and 100 Hz) coincidentally presented to the right thenar eminence. Vibrotactile thresholds were assessed with the skin at a normative temperature of 31 degrees C and at higher temperatures producing pain. Increases in vibrotactile thresholds (mean change = 7.3 dB) occurred at skin temperatures just below and above those that induced pain. Furthermore, absolute-magnitude estimates of suprathreshold vibrotactile stimuli determined during the same experiments showed decreased sensitivity and psychophysical recruitment. The changes are not attributable to attentional or arousal shifts, since they were not associated with changes in auditory thresholds. Furthermore, the changes occurred just below the subjects' pain thresholds (where nociceptors are presumably activated). This over-twofold diminution of vibrotactile sensitivity suggests that heat stimuli capable of inducing pain can significantly diminish taction, perhaps through a "touch gate" in a manner similar to the gate control theory proposed for pain. PMID- 7887056 TI - Modality-dependent modulation of conduction by impulse activity in functionally characterized single cutaneous afferents in the rat. AB - Cutaneous afferents exhibit changes in excitability after impulse activity that are correlated with functional modality but are independent of axonal diameter, as studied in 39 cold fibers and 51 nociceptors of the rat. Latency of conducted impulses was used to indicate changes in axonal excitability caused by electrical stimulation. Stimuli were applied both at fixed frequencies and at the time intervals of impulses previously recorded during response to natural stimulation. Latency increased following both these forms of electrical stimulation, as well as after natural stimulation of the receptive fields. The latency increase was correlated with the number of impulses and the frequency of the preceding discharge in all of 4 nociceptors and 13 cold fibers studied for this feature. Increase of latency by electrical or natural stimulation led to reduced responsiveness to natural stimulation. The magnitude and time course of latency changes were correlated with fiber modality. In 32 nociceptors the latency increased continuously with time during a stimulus train, whereas in 21 cold fibers there was only an initial increase in latency over the first few seconds, after which the latency remained at a plateau even as the firing response continued. Paralleling this slowing, impulse failure occurred more frequently during repetitive stimulation in both A delta and C nociceptors than in velocity matched cold fibers of either class. Based on the magnitude of latency increases during stimulus trains at different frequencies, two distinct patterns were discerned in A nociceptors: "Type II" fibers slowed significantly more than "Type I" or cold fibers. The results support the hypotheses (1) that the pattern of latency changes during activity are signatures for the modality in a given fiber; and (2) that endogenous, activity-dependent processes of the axon contribute to adaptation and encoding in cutaneous sensory afferents. PMID- 7887058 TI - Increased number of sciatic sensory neurons in vitamin-E-deficient rats. AB - The number and morphometric characteristics of sciatic sensory neurons were studied in Vitamin-E-deficient rats. Horseradish peroxidase (HRP) was injected into the sciatic nerves of normal and vitamin-E-deficient rats of the same age, and retrogradely labeled sensory neurons were counted and measured. The study was also carried out in rats that had previously undergone sciatic nerve crush, in order to observe the effects of axotomy on primary sensory neurons. In vitamin-E deficient rats the number of sciatic sensory neurons was significantly higher than normal, with an increase of about 30%, in agreement with a previous finding concerning total population of primary sensory neurons in lumbar dorsal root ganglia (DRGs) of vitamin-E-deficient rats. The increase involved the small cell classes in particular. Axotomy induced similar percentages of neuron loss in normal and in vitamin-E-deficient rats (about 40%). In the latter, death affected small cell classes in particular--that is, the same classes that had increased in number in vitamin-E-deficient rats by comparison with controls. These results, together with previous findings, suggest that neurogenesis may occur in DRGs of vitamin-E-deficient rats. PMID- 7887059 TI - Hairy skin: psychophysical channels and their physiological substrates. AB - Experiments were conducted in which threshold-frequency characteristics were measured on the hairy skin of the forearm of human observers. Thresholds were measured with two stimulus probe areas (2.9 and 0.008 cm2) at three skin-surface temperatures (15 degrees, 30 degrees, and 40 degrees C). The results suggest that whereas glabrous skin uses four distinct channels of information, only three channels may be involved in mediating the sense of touch for hairy skin. The three channels are defined as Ph, (Pacinian, hairy skin), NPh low (non-Pacinian, hairy skin, low frequencies) and NPh mid (non-Pacinian, hairy skin, middle frequencies). In addition, it is proposed that the neural substrates for the three psychophysically characterized channels are, respectively, the Pacinian corpuscle (PC) nerve fibers, the slowly adapting type II (SAII) fibers, and the rapidly adapting (RA) fibers. PMID- 7887060 TI - Diagnosis of pituitary adenomas on touch preparations assisted by immunocytochemistry. AB - Touch preparations from surgically removed pituitary adenomas were studied by both routine staining and immunocytochemistry for all anterior pituitary hormones. The results were correlated with the histologic, histochemical, immunohistochemical and ultrastructural findings. Several features were recognized, some of them applicable in diagnosing various adenoma types: high cellularity, cell monomorphism, nuclear irregularities and heterogeneity of immunoreactivity, all major diagnostic criteria of pituitary adenoma. The presence of numerous fibrous bodies associated with nuclear pleomorphism, multinucleation and peripheral displacement of nuclei, in association with growth hormone (GH) immunopositivity, represent diagnostic criteria for sparsely granulated GH cell adenoma. The "Golgi" pattern of prolactin (PRL) immunopositivity in conjunction with the small size of cell and nucleus and the presence of microcalcifications represents diagnostic features of PRL-secreting adenoma. Cytoplasmic accumulation of hyaline material in association with peripheral distribution of periodic acid-Schiff stain and adrenocorticotropic hormone immunoreactivity is characteristic of sparsely granulated corticotroph cell adenoma. Knowledge and application of the described features may contribute significantly to the diagnostic approach to pituitary adenomas. PMID- 7887061 TI - Washed-biopsy cytology of abdominal lesions. AB - The accuracy of an alternative method of preparing cytologic smears from material collected under laparoscopic examination was studied. "Washed-biopsy" cytology was performed by saline solution lavage of the fragments using a cytocentrifuge. Rich and well-preserved cellularity was obtained. Among 51 cases, cytology revealed 12 benign, 3 suspicious and 36 malignant cases, including 9 true negatives, 3 false negatives and 36 true positives. Suspicious cases were excluded from the analysis. The sensitivity, specificity, positive and negative predictive values, and efficiency, when comparing the cytologic to the definitive diagnoses, were, respectively, 92.3%, 100.0%, 100.0%, 75.0% and 93.7%. We recommend the routine use of the washed-biopsy method in laparoscopic examinations to improve the accuracy of cytologic investigations. PMID- 7887062 TI - Intraoperative immunocytochemistry of cytologic scrape specimens. A rapid immunoperoxidase method for triage and diagnosis. AB - We investigated a rapid immunoperoxidase (IPX) method utilizing a wide variety of antibodies for use on cytologic scrapings of fresh tissue that were submitted for intraoperative frozen section. The handling, fixation and IPX staining of these cytologic scrape specimens are more rapid and convenient than frozen tissue sections and spare tissues that may be of small quantity for appropriate special diagnostic studies (flow cytometry, cell markers, genetic studies, electron microscopy, and so forth). Fresh tissues from normal organs and tumors were scraped with a scalpel blade, smeared on an uncoated glass slide and immersed in 95% alcohol for one minute. Antibodies investigated by this method included: CAM 5.2, AE1/3, keratin 903, desmin, vimentin, HHF-35, CEA, PLAP, NSE, S-100, HMB45, LCA, L26 and UCHL-1. Twenty-three fresh epithelial and mesenchymal tissues from the uterus, colon, tonsil, lymph node, kidney and adrenal gland were examined, along with 29 tumors. There were 21 carcinomas, 3 melanomas, 3 sarcomas and 2 lymphomas. Using the streptavidin-biotin technique with aminoethylcarbazole localization, IPX results were available in 15-20 minutes, comparable to the time required for the reporting of a frozen section diagnosis. Keratins, vimentin, desmin and LCA gave the best results. HMB45 was weakly reactive in one case. This rapid cytologic IPX method may be used as an adjunct to frozen sections and cytologic imprints for intraoperative diagnosis or for efficient triage of poorly differentiated tumors for special studies at the time of frozen section. PMID- 7887063 TI - p53 immunostaining as a marker of malignancy in cytologic preparations of body fluids. AB - The accurate identification of suspicious cells in cytologic preparations is a common problem in diagnostic cytopathology. Recent studies have shown that mutation of the p53 gene may be the most common genetic event in human malignancy. Mutation leads to altered conformation and increased half-life of the p53 protein, resulting in detectability by immunocytochemistry. The usefulness of p53 immunocytochemical staining as a marker of malignancy in the cytologic analysis of body fluids was investigated in the present study. One hundred fifty four serial samples of body fluids submitted for cytologic diagnosis were also examined for p53 immunoreactivity. Of 121 cases reported as cytologically benign, 3 (2.5%) stained positively for p53; 16 samples were cytologically malignant, and 7 (43.7%) of these were positive for p53 (P < .001). Of those reported as suspicious but not conclusively malignant, 4 of 17 (23.5%) showed p53 immunoreactivity. On review, two of the three patients whose samples were benign cytologically yet showed positive p53 staining had histologic evidence of malignancy. The third patient died without a postmortem examination. Of the 17 cytologically suspicious cases, 16 (94.1%) were later proven to be malignant, and p53 was positive in 4 (25%). These results suggest that p53 immunostaining could be of value as a marker of malignancy in the cytologic examination of body fluids. The presence of p53 immunoreactivity in cytologic samples is strongly suggestive of malignancy, though its absence does not exclude neoplasia. PMID- 7887064 TI - Positive peritoneal cytology in stage I carcinoma of the cervix. PMID- 7887065 TI - Fine needle aspiration cytology of non-Hodgkin's lymphomas. A morphologic and immunophenotypic study. AB - To assess the value of fine needle aspiration cytology (FNAC) in the diagnosis of non-Hodgkin's lymphomas (NHL), we retrospectively studied all the cases diagnosed cytologically as NHL in our laboratory during a five-year period (1987-1991). We also traced cases in which FNAC failed to diagnose NHL and where the diagnosis was made subsequently by histopathology. Fine needle aspiration (FNA) was performed on both peripheral/palpable and deeply situated lesions. A total of 164 specimens were studied cytologically, and for 130 of them a histologic report was available. In 83 of the cases, FNA was carried out as part of the initial evaluation, and in 81 the diagnosis of NHL was known and FNA was performed to confirm or exclude a relapse. In 76 cases for which morphology was inconclusive the immunophenotype was assessed by immunocytochemistry. There were three false negative and one false-positive result; in none of them was immunophenotyping performed. No discrepancy was observed in the distinction between low and high grade lymphomas, but this was feasible in only 115 of the 164 specimens studied. We conclude that the method is a feasible, rapid and inexpensive first approach in the evaluation of patients with NHL. FNAC may be substituted for histology in the occasional patient for whom the surgical risk outweighs the inaccuracies of the procedure. PMID- 7887066 TI - Diagnostic value of bladder wash cytology, with special reference to low grade urothelial neoplasms. AB - The diagnostic yield of bladder wash cytology was compared with concurrent bladder biopsy results in 253 consecutive cytology specimens obtained from 208 patients. There was high diagnostic concordance of washes and biopsies for both high grade urothelial neoplasms (26 of 29 cases [90.0%]) and negative specimens (152 of 168 cases [90.5%]). In contrast, bladder wash cytology was interpreted as malignant or suspicious for malignancy in 11 of 33 (33%) patients with low intermediate grade papillary urothelial tumors on biopsy. Additionally, the cytology was considered positive or suspicious for transitional cell carcinoma in 11 cases in which only reactive changes were seen in the concurrent biopsy and follow-up studies (minimum 12-month follow-up), for a false-positive rate of 6.5%. The slides from all discrepant cases were reviewed, with particular attention to background features that may improve the diagnostic sensitivity of cytology in low grade neoplasms. PMID- 7887067 TI - Sputum cytology within and across laboratories. A reliability study. AB - A total of 11 cytotechnologists at sites in Texas (TX1, TX2), California (CA) and Arkansas (AR) were assessed for agreement of six-category diagnoses of sputum cytology slides prepared by the method of Saccomanno. For three observers at TX1 there was more agreement within observers (27-60%) than across observers (13 50%). Within-1 category intraobserver agreement underwent a twofold to threefold increase, to 77-93%; within-2 category agreement was 90-100%. Interobserver within-1 category agreement was 47-92%; within-2 category agreement was 83-100%. Agreement was significantly greater than chance (using kappa) in 69% of all intraobserver and interobserver pairings. Intralaboratory agreement was 40% for CA and 40-57% for TX2. Among pairings of the four sites, the range of interlaboratory agreement was 13-60% over several occasions. The overall range of agreement with the TX1 standard was 17-50% over observers/occasions. Within certain categories, outside agreement with the TX1 standard was 53-90% for normal, 39-80% for squamous metaplasia, 68-84% for mild atypia, 80-100% for moderate atypia and 93-100% for severe atypia or carcinoma. We conclude that agreement is acceptable for extreme atypia, but more training or refinement of the guidelines may be needed, if justified, to better differentiate the lowest categories. Good agreement appears to be as likely for observers with many years of overall experience as for those with high exposure to the Saccomanno method. For potential statistical analyses, the scale should probably be condensed into three to four categories to reduce extraneous variability. PMID- 7887068 TI - Gynecologic cytology from the perspective of the Laboratory Proficiency Testing Program, Ontario, Canada. AB - The accumulated test results from annual proficiency testing of approximately 150 cytology laboratories during the period 1977-1992 were analyzed. Several features of the test program are presented, including the adaptability of the uniform diagnostic terminology that was in use throughout. Observations include the impact of screening by a technologist; the better diagnostic performance generally, but not exclusively, in larger-volume laboratories; the degree of reproducibility of reporting in the laboratory; the ease of diagnosis in some diagnostic categories; and patterns observed in "false negative" and "false positive" rates. The follow-up analysis of suboptimal performance is recorded, and remedial and educational aspects are emphasized. The impact of levels of performance on the specific population being screened is correlated with the data on laboratory caseloads and with hospital vs. nonhospital laboratories. PMID- 7887069 TI - Statistical analysis of data in cervical cytology from the viewpoint of total quality management. AB - As a consequence of widespread dissatisfaction with the high incidence of false negatives in cytologic smear screening, the Clinical Laboratory Improvement Amendments of 1988 were enacted by Congress with specific requirements for quality assurance in the screening of cytologic smears for cervical cancer. This paper examines the process of cervical cytologic screening from a total quality management perspective and suggests the use of several statistical techniques from industrial total quality management for describing and monitoring the process of cytologic smear screening. Several examples are included, and a general approach to implementing these techniques is suggested. PMID- 7887070 TI - An economic model for comparing alternative policies for cervical cytologic smear screening. AB - In this paper a mathematical model is developed to determine the probability that a truly negative cervical cytologic smear will be correctly identified by a system of screening policies that uses one or more cytotechnologists to independently and sequentially prescreen such smears for the detection of cervical cancer. This is an extension of previous work that modeled the probability of detecting a truly positive smear under the same set of policies. In this system any positive reading by a cytotechnologist causes a slide to be rescreened by a pathologist, and if all cytotechnologists declare a slide to be negative, the slide is placed in a pool for random selection of slides to be rescreened by the pathologist. The policy of single screening by a cytotechnologist, with subsequent 10% rescreening of the negative slides, as suggested by the Clinical Laboratory Improvement Amendments of 1988, is thus embedded in the policies that are modeled. In addition, a cost model is developed that takes into account the cost of screening a slide by a cytotechnologist, of rescreening a slide by a pathologist, of a false-positive reading and of a false negative reading. This cost model can be used to determine which policy is optimal for the parameters that pertain to a specific situation. Examples are presented to illustrate the use of the cost model. The results of a computer simulation model are also presented to validate the mathematical results and to display the variability of total cost. PMID- 7887071 TI - Rescreening policies in cervical cytology and their effect on detecting the truly positive patient. AB - In the use of a specific screening policy that relies on the expertise of cytotechnologists and pathologists to examine cytologic smears for the detection of cervical cancer, it is important to know the probability of correctly identifying a positive patient and, for each 1,000 patients, to know the probability distribution, the expected value and the standard deviation of the number of correct identifications. A probability model for the standard 10% rescreening rule mandated by the Clinical Laboratory Improvement Act of 1988 and Medicare was developed and used to evaluate higher screening rates. In addition, the model is applied to an alternative screening policy to study multiple inspections by a specific number of cytotechnologists prior to rescreening by a pathologist. For each policy the probability distribution, expected value and standard deviation of the number of correct identifications per 1,000 positive patients are given. PMID- 7887072 TI - Fine needle aspiration cytology of a subcutaneous metastasis of a malignant Brenner tumor of the ovary. A case report. AB - The fine needle aspiration cytologic findings of a subcutaneous metastasis from a malignant Brenner tumor of the ovary are described. Polygonal cells in clusters and single cells with fine cytoplasmic elongations, moderately pleomorphic nuclei having granular chromatin and multinucleate cells, occasional but prominent grooving of nuclei and many mitotic figures were the salient cytologic features. The cytohistologic correlation was good. The rare metastatic site of this unusual ovarian neoplasm makes this an interesting case and the first of its kind to the best of our knowledge. PMID- 7887073 TI - Cytologic diagnosis of rhabdomyosarcoma in a patient with germ cell tumor. A case report. AB - The development of sarcomas in patients with germ cell tumors is rare but has been reported previously. Theories about its pathogenesis include derivation of the tumor cells from pluripotential germ cells and malignant transformation from teratomatous elements. This report describes the occurrence of rhabdomyosarcoma in a patient with a history of mixed germ cell tumor of the testis who developed a malignant pleural effusion. Cytologic evaluation of the fluid revealed single malignant cells with high nuclear/cytoplasmic ratios and prominent nucleoli. While these features initially suggested a diagnosis of metastatic seminoma, careful cytologic and immunohistochemical examination revealed features consistent with metastatic rhabdomyosarcoma. The exfoliative cytologic findings of other germ cell tumors are also discussed. PMID- 7887074 TI - Necrosis of parotid pleomorphic adenoma following fine needle aspiration. A case report. AB - Fine needle aspiration of parotid tumors is used worldwide and usually is well tolerated by the patient, with no complications. We report a case of pleomorphic adenoma diagnosed by fine needle aspiration that underwent necrosis following the aspiration procedure. PMID- 7887075 TI - Detection of amyloid in gastric brushing material. A case report. AB - A case of gastric amyloidosis in which diagnostic material was detected on gastric brushing material is described. A high index of suspicion and familiarity with the hypocellular, amorphous morphology of amyloid on cytologic smears are essential to the detection of amyloid. Congo red was applied to destained Papanicolaou-stained smears to demonstrate the characteristic green birefringence on cytologically suspicious material. PMID- 7887076 TI - Desmoplastic small round cell tumor presenting in pleural fluid and accompanied by desmin-positive mesothelial cells. PMID- 7887077 TI - Diagnosis of endometrial hyperplasia in women with abnormal uterine bleeding. AB - BACKGROUND: Reliability of hysteroscopy in diagnosing endometrial hyperplasia in women with abnormal uterine bleeding. METHODS: Out of 105 patients with abnormal uterine bleeding 47 showed structural abnormalities. Comparative analysis between hysteroscopic and histological results in 58 women without gross abnormalities has been performed in order to verify sensitivity and specificity of hysteroscopy in the diagnosis of endometrial hyperplasia. RESULTS: Specificity of hysteroscopy in diagnosing endometrial hyperplasia was 84.7% while sensitivity resulted to be 80%. CONCLUSIONS: Women with abnormal uterine bleeding and normal uterine cavity has a low rate (3.4%) of false negative endometrial hyperplasia. On the contrary findings of endometrial hyperplasia at hysteroscopy has a high incidence of false positive (25.8%). In conclusion, abnormal uterine bleeding could cause an increased thickness in endometrium, appearing as hyperplasia on hysteroscopic examination. PMID- 7887078 TI - Operative ultrasonography. PMID- 7887079 TI - GnRH analogs versus expectant management in minimal and mild endometriosis associated infertility. AB - The aim of the present study is to compare the outcome of GnRH analog treatment versus expectant management in infertile patients with minimal and mild endometriosis. From January 1987 to December 1990, 14 patients with stage I and II endometriosis underwent a six-month course of the GnRH analog buserelin, whereas 38 patients underwent expectant management. The two groups were comparable as to mean age of the patients, mean length of infertility prior to diagnosis and mean scores of endometriosis. No major tubal or male factor of infertility was present in any patient. Cumulative pregnancy rates at 12 months were comparable in the two groups (48% for GnRH analog treatment and 42% for expectant management). Expectant management should therefore be considered the most cost-effective option in the management of mild endometriosis-associated infertility. PMID- 7887080 TI - Evaluating test for the fecundating strength of the spermatozoa. PMID- 7887081 TI - Effects of ketoconazole (an imidazole antifugal agent) on the fertility and reproductive function of male mice. AB - Administration of ketoconazole, an imidazole antifungal agent (400 mg/kg b.wt. orally for a period of 60 days) resulted in a significant decline in sperm motility and density in cauda epididymis. A sharp decline in fertility (50% negative) in Ketoconazole treated mice was observed. A significant reduction in the total protein and sialic acid contents of testes, epididymis, seminal vesicle and ventral prostate were noticed. The cholesterol contents of testes were raised while fructose contents of seminal vesicle were reduced significantly. The ketoconazole treatment altered the biochemical milieu of the reproductive tract. The mechanism of action is discussed. PMID- 7887082 TI - Unexplained infertility. PMID- 7887083 TI - Nursing research at the Foothills Hospital. Rigid endoscopes: must they be disassembled prior to sterilization?. Interview by E Henderson. PMID- 7887084 TI - Addiction & re-entry to practice. PMID- 7887085 TI - Questions and answers on nursing practice hours. PMID- 7887086 TI - Response to article "Should nurses be unionized". PMID- 7887087 TI - Nitrous oxide: from frolics to a global concern in 150 years. PMID- 7887088 TI - Risus sardonicus and laughing gas--when nitrous oxide lost its innocence. PMID- 7887090 TI - Nitrous oxide kinetics. PMID- 7887089 TI - The interaction between nitrous oxide and cobalamin. Biochemical effects and clinical consequences. PMID- 7887091 TI - Cerebrovascular response to nitrous oxide. PMID- 7887092 TI - Nitrous oxide and the cardiovascular system. PMID- 7887093 TI - Nitrous oxide: laparoscopic surgery, bowel function, and PONV. PMID- 7887094 TI - Total intravenous anaesthesia--free from nitrous oxide, free from problems? PMID- 7887095 TI - Current status of nitrous oxide for obstetric pain relief. PMID- 7887096 TI - Nitrous oxide analgesia in dental practice. PMID- 7887097 TI - Nitrous oxide in pre-hospital care. PMID- 7887098 TI - Nitrous oxide: at threat to personnel and global environment? PMID- 7887099 TI - Anaesthesia for abdominal vascular surgery in patients with coronary artery disease (CAD), Part I: Isoflurane produces dose-dependent coronary vasodilation. AB - The effects of anaesthesia for major abdominal vascular surgery on coronary flow regulation and mechanisms of myocardial ischaemia were studied in 56 patients with CAD, using a randomized, partly double-blinded protocol. After induction with fentanyl (3 micrograms.kg-1) and thiopentone (2-4 mg.kg-1) and tracheal intubation, principal anaesthetics were nitrous oxide/oxygen (60/40) with isoflurane (n = 20), halothane (n = 19) or fentanyl (15-20 micrograms.kg-1) (n = 17). Conventional invasive techniques and coronary venous retrograde thermodilution were used to assess systemic and coronary haemodynamics. Coronary vascular resistance was estimated from myocardial oxygen extraction. Myocardial ischaemia was diagnosed by 12-lead ECG and/or anterior wall motion abnormalities by cardiokymography and/or myocardial lactate production. When adjustment of anaesthetic dose was insufficient for haemodynamic control, i.v. phenylephrine and nitroglycerine were administered to treat hypotension and hypertension or cardiac failure respectively. Measurements were performed at four specific intervals; awake, before surgery and 10 and 30 min after abdominal incision. Comparable changes of systemic haemodynamics and myocardial oxygen consumption were observed in the three groups. Coronary vasodilation was evidenced in isoflurane patients only and was linearly dose-dependent (P < 0.001). Partial Least Squares Projections to Latent Structures modelling with cross validation confirmed this dose-dependency and ruled out a clinically measurable influence by intervention drugs or simultaneous systemic haemodynamic abnormalities. The incidence of myocardial ischaemia during anaesthesia and surgery was comparable in the three groups (35, 37 and 24%, respectively) and there was an association with systemic haemodynamic aberrations in 19 of the 27 ischaemic episodes. In contrast to ischaemic halothane and fentanyl patients, isoflurane patients with ischaemia had significantly lower myocardial oxygen extraction (P = 0.008 and P = 0.001, respectively), indicating that the oxygen extraction reserve was not utilized in a normal way during ischaemia. PMID- 7887100 TI - Anaesthesia for abdominal aortic surgery in patients with coronary artery disease, Part II: Effects of nitrous oxide on systemic and coronary haemodynamics, regional ventricular function and incidence of myocardial ischaemia. AB - This study examines the effects of nitrous oxide on haemodynamics, anterior left ventricular (LV) function and incidence of myocardial ischaemia in abdominal vascular surgical patients with coronary artery disease. Forty-seven patients were randomly assigned to isoflurane-fentanyl anaesthesia with nitrous oxide oxygen vs air-oxygen (control). Systemic and coronary haemodynamics, 12-lead ECG, LV anterior wall motion by cardiokymography (CKG) and myocardial lactate balance were recorded at four intervals: before and during anaesthesia and 10 and 30 minutes into surgery. Systemic haemodynamics were controlled by anaesthetic dose, and, when insufficient, by i.v. nitroglycerine (NG) in case of LV failure (PCWP > 18 mmHg) and by phenylephrine during hypotension. We found that nitrous oxide was associated with greater need for i.v. nitroglycerin (patients: P = 0.031, episodes P = 0.005) and more myocardial ischaemia (patients P = 0.012, episodes P = 0.001) despite systemic and coronary haemodynamics comparable to the control group. We conclude that nitrous oxide, known to have both sympathomimetic and cardiodepressive actions, produced cardiodepression in the face of sympathetic stimulation. Our study design did not allow to conclude if myocardial ischaemia was the consequence of increased wall stress or a reason for the observed LV dysfunction. The higher incidence of introperative myocardial ischaemia and need for NG did not cause increased cardiac morbidity. PMID- 7887101 TI - Intradermal anaesthesia: comparison of several compounds. AB - OBJECTIVE: To compare the efficacy of different local anaesthetics to produce intradermal anaesthesia for venous cannulation and the discomfort associated with skin infiltration. DESIGN: Randomized, double blind study. SETTING: Induction room of a university hospital. PATIENTS: Convenience sample of 600 patients (18 65 years; ASA I-II) scheduled for elective surgery. INTERVENTIONS: Patients received one of six preparations: 0.9% saline, 1% prilocaine (Xylonest), 1% lidocaine (Xylocain), 1% mepivacaine-1 (Meaverin), 1% mepivacaine-2 (Scandicain), 1% procaine (Novocain). A skin wheal was raised on the dorsum of the hand by injecting 0.1 ml intradermally and 0.1 ml subcutaneously via a 27-g hypodermic needle. 60 seconds later an 18-g intravenous cannula was passed through that skin wheal into a vein. MEASUREMENTS: A visual analog scale (VAS) for pain (0 = no pain/10 = most pain imaginable) was used to assess pain elicited by raising the skin wheal and inserting the cannula. MAIN RESULTS: With regard to analgesic potency all five local anaesthetics were comparable (mean VAS-score 1.7-2.09) and effective when compared to 0.9% saline (mean VAS-score 4.2; P < 0.001). Infiltration pain was least with mepivacaine-1 (mean VAS-score 1.0; P < 0.001) and highest with procaine (mean VAS score 2.7; P < 0.001). CONCLUSIONS: Of the local anaesthetics tested, Mepivacaine-1 is the drug of choice for skin infiltration as its injection elicits least discomfort. PMID- 7887102 TI - Thoracic epidural analgesia compared with patient controlled intravenous morphine after upper abdominal surgery. AB - Twenty-one ASA I or II patients undergoing upper abdominal surgery were studied for 24 hours after operation. They were entered into a prospective, randomised study of patient-controlled intravenous morphine compared with continuous thoracic epidural fentanyl combined with 0.2% bupivacaine. Pain relief was superior in the bupivacaine series (P < 0.05) throughout the 24 hour study period and this was associated with significantly greater pulmonary ventilation compared with the PCA series. Forced expiratory parameters were reduced in both series after the operation but significantly less so in the epidural group. There was a reduced incidence of emetic symptoms in the epidural group (P < 0.05) but the incidence of other minor side effects did not differ significantly. Thoracic epidural fentanyl/bupivacaine results in significantly better analgesia than patient-controlled intravenous morphine. PMID- 7887103 TI - Bupivacaine wound infiltration in thyroid surgery reduces postoperative pain and opioid demand. AB - Control of postoperative pain is an important element in preventing the modification of the excitability of the dorsal horn neurons. We studied the efficacy of bupivacaine 0.5% wound infiltration for postoperative pain management following thyroid surgery. Forty consecutive ASA I-II patients, scheduled for thyroidectomy, were assigned randomly to two groups. Group I (n = 20) consisted of patients receiving bupivacaine 0.5% (10 ml) wound infiltration at the end of surgery and group II (n = 20 included patients without infiltration. The patients did not know whether the wound had been anaesthetized or not. All patients received balanced inhalational anaesthesia, including fentanyl (a total dose of up to 4 micrograms.kg-1). Postoperative pain medication included morphine IV or IM, as needed. Twenty-four hours after surgery the worst pain was recorded using a visual analogue scoring system, from 0 to 10. Twenty-four hour postoperative morphine requirement was recorded. Groups did not differ in demographic data. Pain scores significantly different in the two groups. In group I, the mean pain score was 3.7 +/- 1.6 compared with 6.9 +/- 1.7 in group II (P < 0.05). Only six patients (30%) in group I received opioids and only one of these (5%) had a pain score above 5. In comparison, 18 patients (90%) in group II received morphine during the first postoperative day. The local injection of bupivacaine corresponds to a block of the superficial branches of the cervical plexus. This study demonstrated a simple, efficient and safe way to reduce pain perception following a thyroidectomy. PMID- 7887104 TI - Inhibitory effects of halothane on high(K+)-induced canine tracheal smooth muscle contraction and intracellular Ca2+ increment. AB - Halothane is a potent bronchodilator. The effects of halothane on isolated canine tracheal smooth muscle contraction and intracellular Ca(2+) increment induced by a high concentration of K+ were investigated to clarify how this anaesthetic decreases intracellular Ca2+ concentration ([Ca2+]i), an important second messenger. The tension of the muscle strips was measured using an isometric transducer, and [Ca2+]i was measured using a surface fluorescence spectroscopy. Exposure to a 72.7 mM K+ solution increased muscle tension and [Ca2+]i. Halothane (1,2,3 and 4% at the vaporiser) was introduced by bubbling in the presence of the 72.7 mM K+, and significantly decreased both this elevated muscle tension and the [Ca2+]i in a concentration-dependent manner. Similarly, slowly decreasing concentrations of K+ (48.5, 36.4, 24.2 and 18.2 mM) significantly decreased both of these variables. There was no significant difference between the slopes of the two regression lines of changes in muscle tension and changes in [Ca2+]i. From the evidence that tonic increase in [Ca2+]i by high concentrations of K+ is due to the influx of Ca2+ via L-type voltage channels, halothane may modify the L type channels to decrease Ca2+ influx. In conclusion, halothane inhibits the high K(+)-induced canine airway smooth muscle contraction by decreasing [Ca2+]i. The decrease in [Ca2+]i by halothane might be due to inhibition of voltage-operated channels, especially the L-type channels. PMID- 7887105 TI - Platelet activation in major surgical stress: influence of combined epidural and general anaesthesia. AB - Platelets are activated in surgery releasing vasoactive substances such as serotonin and thromboxane. Platelets become temporarily hypoaggregable during surgery followed by a postoperative hyperaggregability. Local anaesthetics are known to inhibit platelet function but earlier reports are conflicting. In order to study the impact of the combined use of general and regional anaesthesia on platelet function during major surgery 16 otherwise healthy patients were randomised to either general anaesthesia (GA) (n = 8) or GA combined with epidural anaesthesia (GA+EPI) (n = 8) for elective upper abdominal surgery. Cyclic 3',5' adenosine monophosphate, plasma glucose, plasma cortisol and the rate pressure product (RPP) were markers of the stress response. ADP-induced platelet aggregation and the release products beta-thromboglobulin, serotonin and thromboxane 2 were measured in plasma before and during as well as for 3 days after surgery. A marked stress response was noted in both groups and epidural anaesthesia (EPI) only reduced the rate pressure product (RPP). Platelet aggregation was reduced during surgery, a little more so in the GA+EPI group. Postoperatively both groups showed significant hyperaggregability. The release products were not significantly influenced by regional anaesthesia. In conclusion epidural as combined with general anaesthesia affects platelet responses to major abdominal surgery only to a minor extent, although it may attenuate the haemodynamic response. PMID- 7887106 TI - Thoracic epidural analgesia in aortocoronary bypass surgery. I: Haemodynamic effects. AB - Tachycardia and hypertension may cause myocardial ischaemia in patients with coronary heart disease going through major surgery. Thoracic epidural analgesia (TEA) has been reported to be beneficial in this situation. The haemodynamic effects of TEA in aortocoronary bypass surgery were investigated in 30 male patients < 65 years old and with ejection fraction > 0.5. They were randomized into 3 groups: the high dose fentanyl (HF) group receiving high-dose fentanyl (55 micrograms.kg-1) anaesthesia, the HF+TEA group receiving the same fentanyl dose+TEA with 10 ml bupivacaine 5 mg.ml-1 followed by 4 ml every hour, and the low dose fentanyl (LF) + TEA group receiving low-dose fentanyl (15 micrograms.kg 1) anaesthesia+TEA. Haemodynamic parameters, the use of vasoactive and inotropic drugs and fluid balance were followed during the operation and for 20 h postoperatively. Before bypass the only significant difference between groups was a higher mean pulmonary arterial pressure in the HF+TEA group and a lower systemic vascular resistance (SVR) in the LF+TEA group, both compared to the HF group. 89% of epidural group patients needed small doses of ephedrine whereas more HF group patients were given nitroglycerine. During bypass SVR and mean arterial pressure (MAP) were significantly higher and pump flow lower in the HF group compared to the LF+TEA group. More ketanserin to HF group patients and methoxamine to epidural group patients were given. After bypass heart rate increased in all groups. Lower MAP 0.5 h after bypass and higher filling pressures in the early post bypass period in the epidural groups, most pronounced in the HF+TEA group, were noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887107 TI - Thoracic epidural analgesia in aortocoronary bypass surgery. II: Effects on the endocrine metabolic response. AB - Thoracic epidural analgesia (TEA) may offer haemodynamic benefits for patients with coronary heart disease going through major surgery. This may-in part-be secondary to an effect on the endocrine and metabolic response to surgery. We therefore investigated the effect of TEA on the endocrine metabolic response to aortocoronary bypass surgery (ACBS). Thirty male patients (age < 65 years, ejection fraction > 0.5) were randomized into 3 groups; the HF group receiving a high dose fentanyl (55 micrograms.kg-1) anaesthesia, the HF+TEA group with the same fentanyl dose+TEA with 10 ml bupivacain 5 mg.ml-1, followed by 4 ml every hour, and the LF+TEA group receiving fentanyl 15 micrograms.kg-1 + TEA. Adrenalin, noradrenalin, systemic vascular resistance (SVR), glucose, cortisol, lactate and free fatty acids were followed during the operation and for 20 h postoperatively. A significant increase in adrenalin, noradrenalin and SVR was found in the HF group whereas this increase was blocked in both epidural groups. An increase in glucose and cortisol was noticed in all groups, but the increase was delayed in the epidural groups. Our results suggest that a more effective blockade of the stress response during ACBS is obtained when TEA is added to general anaesthesia than with high dose fentanyl anaesthesia alone. PMID- 7887108 TI - A new hybrid anaesthetic circuit for a low-flow rebreathing technique. AB - The coaxial Mapleson D (Bain) circuit is close to an ideal anaesthetic breathing circuit but it requires a high fresh gas flow (VF). The CO2 absorber circuit can be used with a low VF but the patient end is clumsy and hyperventilation is common unless a small tidal volume (VT) and a low respiratory frequency (f) is used. To overcome these problems a new hybrid anaesthetic circuit has been constructed. The new system has a slender coaxial patient end, connected to a Y piece and a CO2 absorber circuit with unidirectional valves. The VF supply runs inside the coaxial tube to the patient end, similar to the Bain circuit. The new circuit was tested with simulated controlled ventilation in a lung model and compared to an absorber circuit, an absorber circuit with an added 300 ml dead space (VD) and a Bain circuit. The fraction of end tidal CO2 (FECO2) was measured as a function of VF. With VF 11 min-1, VT 10 ml.kg-1 and f 12 breaths min-1 a simulated 70 kg patient had an FECO2 of 4.8% and a 40 kg patient 5.5% with VF 21.min-1. At zero VF the new system was equal to an absorber circuit with 300 ml VD. With increasing VF the FECO2 in the new circuit decrease towards the absorber circuit values. The new system combines the benefits of the Bain circuit with those of a low flow CO2 absorber circuit and offers flexibility in the choice of combinations of VT, f and VF. PMID- 7887109 TI - Lignocaine-induced convulsion does not induce c-fos protein (c-Fos) in rat hippocampus. AB - Recent studies have shown that proto-oncogene c-fos mRNA is induced in the central nervous system by a variety of stimuli including generalised convulsions. In this study, the expression of c-fos protein (c-Fos) following lignocaine induced convulsions was examined and compared with that following convulsions induced by non-anesthetic convulsants, such as pentylenetetrazol, kainic acid and electroconvulsive shocks, in rat brain. Administration of 120 mg.kg-1 lignocaine by the intraperitoneal route induced generalised convulsions in all rats examined within 10 min. C-Fos was markedly induced in the piriform cortex and amygdala, and slightly induced in the neocortex and thalamus, while no c-Fos expression was observed in the hippocampus. In contrast, c-Fos expression following generalised convulsions induced by non-anaesthetic convulsants was very marked in the hippocampal region, piriform cortex and amygdala, and extended to the thalamus and neocortex. These results contradict those of previously reported local cerebral metabolic studies using 2-deoxyglucose as a metabolic marker, and suggest that lignocaine-induced convulsions, unlike those induced by non anaesthetic convulsants, may not cause severe sequelae (plastic changes) in the hippocampus. PMID- 7887110 TI - The redistribution of granulocytes following E. coli endotoxin induced sepsis. AB - Infusion of endotoxin elicits granulocytopenia followed by increased numbers of granulocytes in peripheral blood. The purpose of this study was to investigate the redistribution and sequestration of granulocytes in the tissues following E. coli endotoxin induced sepsis. From 16 rabbits granulocytes were isolated, labelled with Indium and reinjected intravenously. Eight rabbits received an infusion of E. coli endotoxin 2 micrograms kg-1 while eight received isotonic saline. The redistribution of granulocytes was imaged with a gamma camera and calculated with a connected computer before and 2 and 6 hours after infusion of endotoxin or saline. Serum cortisol and interleukin-1 beta were measured. In another seven rabbits, respiratory burst activity and degranulation of granulocytes were measured prior to and from 5 min to 6 hours after infusion of E. coli endotoxin 2 micrograms kg-1 BW. Following infusion of endotoxin, the number of granulocytes in peripheral blood decreased from 2.44 to 0.064 x 10 l-1 two hours later. Within 5 min after infusion the overall oxidative burst of the peripheral blood granulocytes was increased and the granularity had decreased. Serum cortisol and interleukin-1 beta increased significantly. The radioactivity of labelled cells in the bone marrow and spleen decreased to 83.1% and 91.6% of initial values. At the same time there was a transient sequestration of labelled granulocytes in the lungs reaching 117.6% of initial values. The radioactivity of the liver increased continuously to 118.4%. The results indicate that endotoxin induces an efflux in activated granulocytes from peripheral blood, bone marrow and spleen to the lungs and liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887111 TI - Effects of propofol and thiopentone on polymorphonuclear leukocyte functions in vitro. AB - Anesthetic agents may impair host defense mechanisms including polymorphonuclear leukocyte (PMNL) function. We have studied the effects of thiopentone and propofol in low (thiopentone 10 mg/L, propofol 2 mg/l) and high (thiopentone 40 mg/L, propofol 6 mg/L) clinically relevant concentrations on PMNL adherence, chemotaxis, phagocytosis and killing in vitro. The results demonstrated that thiopentone in both concentrations significantly decreases all PMNL functions tested and had a direct influence on the PMNLs in terms of their chemotactic response. In contrast, propofol decreases significantly only PMNL chemotaxis but not adherence, phagocytosis and killing. The effect of propofol was not attributable to the lipid carrier vehicle, as Intralipid with same formulation had no effect on PMNL function. We conclude that propofol is a relatively safe agent from the viewpoint of PMNL function in vitro, which may be of potential clinical benefit. PMID- 7887112 TI - Acid aspiration syndrome prophylaxis in gynaecological and obstetric patients. A Norwegian survey. AB - Clinical practice and attitudes of Acid Aspiration Syndrome (AAS) prevention in connection with gynaecological and obstetric surgery were surveyed in all Norwegian departments of anaesthesia. General anaesthesia with rapid-sequence intubation using succinylcholine and cricoid pressure was the preferred method for all emergency surgery, except Caesarian section (C-section) where 58% of the departments reported use of spinal or epidural anaesthesia if time allowed for its use. Chemoprophylaxis was more often used before emergency C-section (60%) than before emergency gynaecological surgery (14%), and mostly consisted of the antacid sodium citrate given alone. Seventy-six percent of the departments used mechanical emptying of the stomach before emergency gynaecological surgery and 44% before emergency C-section. While all responders considered recent intake of a "light breakfast" in an elective patient to be a risk factor of AAS indicating delay of surgery or use of specific precautions like regional anaesthesia, rapid sequence intubation, or chemoprophylaxis, 52-72% of the responders considered obesity, dyspepsia, recent water intake, smoking or use of chewing gum to be risk factors as well. We think this survey demonstrates a need for consensus discussions of AAS prophylaxis. PMID- 7887113 TI - The agreement between adductor pollicis mechanomyogram and first dorsal interosseous electromyogram. A pharmacodynamic study of rocuronium and vecuronium. AB - The agreement between evoked adductor pollicis mechanomyogram and first dorsal interosseous evoked electromyogram (EMG) was evaluated during a pharmacodynamic study of rocuronium and vecuronium. In the first place the effective doses of rocuronium producing 50% and 90% block (ED50 and ED90, respectively) were established in 32 neurolept anaesthetized patients from the adductor pollicis mechanomyogram and the first dorsal interosseous EMG area and amplitude. Secondly, limits of agreement between the two methods were evaluated from the mean difference between methods +/- 2 s.d. in 20 patients during onset of block following 2 x ED90 of rocuronium and vecuronium, and during recovery from the last supplementary dose of 1/2 x ED90. Limits of agreement show how much the EMG may be above or below the mechanomyogram. No differences were found between mechanomyographical and EMG based ED50 (0.20 mg kg-1) and ED90 (0.30-0.32 mg kg 1), respectively. The first EMG train-of-four (TOF) response overestimated block at 25% recovery and underestimated block at 75% and 90% recovery by only 3-7%. Limits of agreement suggested that the EMG may be 7-8% above or below the mechanomyogram during onset compared to 12-17% during recovery. The EMG TOF ratio lagged behind that of the mechanomyogram by 0.05 at TOF ratios below 0.50. No difference was found between methods at a TOF ratio of 0.75. Limits of agreement indicated that the EMG TOF ratio may be 0.12-0.15 above or below that of the mechanomyogram. Agreement between the amplitude and the area of the EMG were better than between the mechanomyogram and the EMG. Evaluation of the time courses of action showed that rocuronium had a faster onset of action than vecuronium (1.8 min compared to 2.8 min) while duration of action and reversal were similar. In conclusion, the first dorsal interosseous EMG amplitude and area can be used to assess rocuronium and vecuronium block. PMID- 7887114 TI - Respiratory and haemodynamic effects of conventional volume controlled PEEP ventilation, pressure regulated volume controlled ventilation and low frequency positive pressure ventilation with extracorporeal carbon dioxide removal in pigs with acute ARDS. AB - The purpose of this study was to evaluate whether any benefit of low frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV ECCO2R) existed over either volume controlled ventilation (VCV) with measured best-PEEP or pressure regulated volume controlled ventilation (PRVCV) with an inspiration/expiration (I/E) ratio of 4:1, with respect to arterial oxygenation, lung mechanics and haemodynamics, in acute respiratory failure. Fifteen adult pigs were used for the study. Respiratory failure was induced by surfactant depletion by repeated lung lavage. The different therapeutic approaches were applied randomly to each pig for 1 h. Measurements of gas exchange, airway pressures and haemodynamics were performed during ventilatory and haemodynamic steady state. Paco2 was kept constant in all modes. At almost similar total-PEEP, Pao2 values were significantly higher with LFPPV-ECCO2R compared to VCV with best PEEP. Peak inspiratory pressure (PIP) and intrapulmonary pressure amplitude defined as the difference between PIP and total-PEEP were significantly lower with PRVCV and LFPPV-ECCO2R compared to VCV with best-PEEP. There was no significant difference between the modes concerning cardiocirculatory parameters. PRVCV with I/E ratio of 4:1 and LFPPV-ECCO2R proved to be better modes to achieve better gas exchange and lower PIP at lower intrapulmonary pressure amplitudes. It is concluded that PRVCV is an adequate form of treatment under these experimental conditions imitating acute respiratory failure, without necessitating other invasive measures. PMID- 7887115 TI - High dose vecuronium for rapid sequence intubation--is it safe? PMID- 7887116 TI - Circulatory drugs modify the hemodynamic actions of alfentanil combined with vecuronium or pancuronium. AB - To verify, whether drugs used to treat hypertension, coronary disease, and heart insufficiency modify the hemodynamic effects of the combinations alfentanil vecuronium and alfentanil-pancuronium, 36 patients taking these drugs (most often beta-adrenergic antagonists) were randomized to receive either vecuronium or pancuronium in connection with ophthalmic surgery. In comparison with healthy patients, the heart rate and arterial pressure changes during induction, intubation and surgery appeared to be smoothed. Heart rate and arterial pressure equaled between the study groups, indicating a block of the sympathomimetic actions of pancuronium. One third of the patients receiving vecuronium exhibited nodal rhythm and some of them showed slow heart rates during intense surgical stimulation. Pancuronium offered protection against bradyarrhythmias. PMID- 7887117 TI - Double-blind comparison between inverse sequence induction with atracurium and rapid sequence induction with succinylcholine. AB - In this double-blind randomized study of 60 patients, a new rapid sequence induction technique (RSI), the so-called inverse sequence induction technique (ISI), is compared to the standard RSI using succinylcholine (SUX). All patients were premedicated with midazolam 0.07 mg.kg-1 and morphine 5 mg im. The patients in the ISI group received atracurium 0.6 mg.kg-1 followed after 1 min by thiopental 5 mg.kg-1. The patients in the SUX group were precurarized with atracurium 0.06 mg.kg-1 followed after 3 min by thiopental 5 mg.kg-1 and succinylcholine 1.5 mg.kg-1. In both groups patients were intubated 1 min after thiopental injection by a trained blinded anesthetist who graded intubation conditions from 1 (excellent) to 4 (impossible). Intubation scores (ISI: 1 and SUX: 1 (range 1-3)) and intubation times (from laryngoscopy to cuff inflation: ISI 18 +/- 10 s, SUX 19 +/- 8 s) as well as mean arterial pressure, heart rate, SpO2 and EtCO2 values were not significantly different between groups. Three patients in the ISI group failed to maintain a handgrip. In both groups all patients were able to cough forcefully at the time of thiopental injection. These data emphasize the reliability and safety of ISI as an alternative for RSI when succinylcholine is contraindicated. However, the unpleasantness of awake partial curarization may limit its acceptance. PMID- 7887118 TI - Edrophonium is better than neostigmine to antagonize residual vecuronium induced neuromuscular block. AB - Edrophonium (EDR) has the advantages of a quick onset of action and reduced cholinergic effects compared to neostigmine (NST) when they are used to antagonize neuromuscular block (NMB). There are few studies about antagonism of very weak residual NMB. Therefore we compared hemodynamic stability, train-of four (TOF) characteristics and reversal time (time from administration of antagonists to train-of-four-ratio (TR) at least 0.70) of EDR 0.5 mg kg-1 + atropine (ATR) 0.007 mg kg-1 to NST 0.04 mg kg-1 + glycopyrrolate (GLY) 0.008 mg kg-1 when they were used to antagonize a residual vecuronium (VEC)-induced NMB (T1 25-75%). The NMB was monitored in 64 patients using the evoked electromyogram of the hypothenar muscle of the hand. An adequate antagonism was defined as a TR of 0.70 or higher. Heart rate was significantly higher in NST+GLY group 2 min after administration of the antagonists in comparison with the EDR+ATR group. The advantages of EDR (higher T1, TR and percentage of patients with an adequate recovery) were obvious during the first 5 min of reversal time. Therefore we conclude, that under the conditions described in the present study, EDR antagonizes residual VEC induced NMB faster than NST. PMID- 7887120 TI - Control of drug-resistant epilepsy after head injury with intravenous nimodipine. AB - The present report describes a young child who developed generalized epileptic seizures in the course of severe head injury. The start of epileptic seizures was associated with the occurrence of acute hyponatremia and hypoosmolality due to excessive Desmopressine administration. The seizures resistant to conventional therapy resolved completely with intravenous nimodipine infusion. PMID- 7887119 TI - Effects of intravenous clonidine on the secretion of growth hormone in the perioperative period. AB - Growth hormone (GH) improves the metabolic and immunitary parameters in the postoperative period. Clonidine, a central acting alpha 2-adrenoceptor agonist stimulates GH release and is currently used as a screening test for GH deficiency. A continuous iv infusion of clonidine may lead to a sustained increase in GH secretion during the perioperative period. With institutional approval and after informed consent, 20 healthy (ASA 1) patients scheduled for functional middle ear surgery under deliberate hypotensive anesthesia were studied. The anesthetic technique consisted of isoflurane, fentanyl and atracurium. Patients were randomly assigned to two groups. In group 1, hemodynamic stabilisation was obtained with a loading dose of clonidine (4 micrograms.kg-1 in 30 min) and maintained with an infusion of 1 microgram.kg-1.h 1. In group 2, a loading dose of labetalol 0.2 mg.kg-1 was followed by an infusion of 0.1 mg.kg-1.h-1. These infusions were stopped 30 min. before the end of the procedure. GH and glucose concentrations were assayed before the induction of anesthesia, after the loading dose and every 30 min. during the procedure and after the recovery during 2 hours. Serum clonidine levels were assayed after the loading dose, 1 and 3 hours later. Somatomedin C (IGF-I) concentration was measured before the induction and in the first postoperative morning along with GH, glucose and clonidine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887121 TI - Extracellular matrix regulates cell morphology, proliferation, and tissue formation. AB - The roles of extracellular matrix (ECM) components such as collagen, elastin, proteoglycan, and adhesive glycoprotein in the regulation of cell morphology, proliferation, and tissue formation were investigated. On a basement membrane gel, the perisinusoidal stellate cells (lipocytes, fat-storing cells, Ito cells) formed a mesh-like structure, proliferated slowly, and synthesized only a small amount of collagen. On polystyrene or type I collagen-coated culture dishes, the stellate cells spread well and extended cellular processes. The stellate cells proliferated better and synthesized more collagen on type I collagen-coated dishes than on polystyrene dishes. Co-cultures of hepatic parenchymal cells and fibroblasts formed a three-dimensional hepatic cord-like architecture in the medium supplemented with a long-acting vitamin C derivative, L-ascorbic acid 2 phosphate (Asc 2-P). Skin fibroblasts formed a three-dimensional dermis-like structure in the medium supplemented with Asc 2-P. Asc 2-P stimulated collagen synthesis of these cells. The stimulative effects of Asc 2-P on tissue formation were suppressed when collagen synthesis in these cells was inhibited. These data indicate that ECM can regulate cell morphology, proliferation and tissue formation. Regulation of cellular functions in other tissues such as mammary gland, thymus and prostate by ECM was also reviewed, and the molecular mechanisms of the regulation are discussed. PMID- 7887123 TI - Bronchial tree, lobular division and blood vessels of the nutria (Myocastor coypu) lung--evidence for the individual nature of the bronchioles in the upper and middle lobes. AB - Four nutria (Myocastor coypu) lungs were examined. The right lung consists of the upper, middle, lower and accessory lobes, whereas the left lung consists of the upper, middle and lower lobes. These lobes are completely separated, and the upper and middle lobes are particularly well developed on either side. Each lung has four bronchiole systems, i.e., dorsal, lateral, ventral and medial. The upper lobe is formed by the first bronchiole of the dorsal bronchiole system. The middle lobe is formed by the first bronchiole of the lateral bronchiole system. The accessory lobe is formed by the first bronchiole of the ventral bronchiole system. The remaining bronchioles of the four bronchiole systems constitute the lower lobe. The right and left pulmonary arteries run across the ventral side of the upper lobe bronchiole and then across the dorsal side of the middle lobe bronchiole. Thereafter the pulmonary arteries run along the dorsolateral side of the bronchi. During their course, pulmonary arteries give off branches running mainly along the lateral or dorsal side of each bronchiole. The pulmonary veins run mainly along the ventral or medial side of the bronchioles, and between them. PMID- 7887122 TI - Gradient of mineral contents of vertebral column with special reference to intervertebral discs. AB - To study quantitatively the mineral elements in the vertebral column, we examined the vertebrae and intervertebral discs resected from three normal cadavers which died at middle age, by inductively coupled plasma atomic emission spectrometry. The relative contents of calcium, phosphorus, and sodium in vertebrae were high in the order from cervical to lumbar vertebrae. The ratios of calcium per phosphorus were 1.80 +/- 0.25 in cervical vertebrae, 1.59 +/- 0.22 in thoracic vertebrae, and 1.23 +/- 0.24 in lumbar vertebrae. The ratio of cervical vertebrae was the highest among them. In regard to intervertebral discs, both the relative contents of calcium and phosphorus were very much higher in the intervertebral discs between the 4th and 8th thoracic vertebrae than the others. PMID- 7887124 TI - Blood cell-producing site in the land slug, Incilaria fruhstorferi. AB - Blood cell-producing site in a yeast-particle-injected slug, Incilaria fruhstorferi, was studied by light and electron microscopy, in vivo and in vitro. Cells lining the vascular system and hemocoel wall were discontinuous, scattered, and morphologically resembled fibroblasts. One hour after injection of yeast particles as foreign material, the lining cells projected into the lumen and 3 h later, the cells were gradually released from the wall. They were morphologically similar to macrophage-like cells that phagocytose foreign material. In tissue culture of the hemocoel wall from yeast-injected slugs, cells that migrated from the explants consisted mainly of fibroblast- and macrophage-like cells. These two kinds of cells were weakly positive to non-specific esterase reaction, whereas circulating hemolymph cells were strongly positive. After administration of bromodeoxy-uridine (BrdU), labeled cells were most commonly found in the ventral side of the body and around the hemal space of the center of the dorsal wall. These results agree with our hypothesis that fibroblasts in the connective tissue of the hemocoel wall of the land slug can transform into macrophages of hemolymph. PMID- 7887125 TI - [Anatomical studies on the thumb muscles of the human hand]. AB - The thenar muscles in 34 cases of 25 human adults were dissected using a stereoscopic microscope. The main supplying branch of the median nerve is often called the recurrent branch because of its characteristic recurrent course, and it enters the muscles between the abductor pollicis brevis and the superficial head of the flexor pollicis brevis. The other branch of the median nerve enters the latter muscle directly close to the tendon of the flexor pollicis longus laterally. This is called the direct branch, and was observed in 32 cases. Of these 32, it passed medial to the tendon in 7 cases. The deep terminal branch of the ulnar nerve supplies the transverse and the oblique heads of the adductor pollicis. One of the branches passes laterally piercing through the latter, and connects with the direct branch of the median nerve under the tendon of the flexor pollicis longus. The anastomosis between the two nerves was observed in 31 cases (91%). The obtained results concerning the nerve supply of the thenar muscles are summarized in Table 1. As seen in this table, the boundary of the supplying area between the median and ulnar nerves almost coincides with the position of the tendon of the flexor pollicis longus. In the other three cases in which a thick anastomosis, about 1 mm in thickness, existed between the median and ulnar nerves in the forearm (Martin-Gruber anastomosis), remarkable expansion of the supplying area of the ulnar nerve within the thenar muscles was observed, as seen in Table 2. According to the descriptions from clinical fields, the opponens pollicis and even the abductor pollicis brevis are sometimes supplied by the ulnar nerve. Such an extreme case may be explained by the existance of the anastomosis described above. The palmar interosseous muscle of the thumb has been described in textbooks. In this study, it is identified as the muscle fascicle of the adductor pollicis dorsal to the princeps pollicis artery, and was observed in 22 cases (65%). The macaca fuscata was also examined in 5 cases. In contrast to humans, all the thenar muscles can be identified without difficulty because no fusions are observed among them and because the nerve supply for each muscle is fairly constant. PMID- 7887126 TI - Electron microscopic studies on Sharpey's fibers in the alveolar bone of rat molars. AB - The fine structure of Sharpey's fibers in the alveolar bone of rat molars were observed by electron microscope. The fixed samples were three-dimensionally observed with a scanning electron microscope (SEM) after NaOH treatment. The penetrating Sharpey's fibers in the alveolar bone appeared distinctly. The fibers penetrated straight and/or branched in the alveolar bone. The Sharpey's fiber bundles ran nearly perpendicular to the bone matrix fiber bundles. The other fixed samples were embedded in polyester resin, ground and observed by backscattered electron signals in an SEM (BSE). In the BSE images, even thin Sharpey's fibers deeply penetrating the alveolar bone were hypomineralized. The fine ultrastructure of fibers were also observed by a transmission electron microscope (TEM). It was suggested that the three-dimensional structure of Sharpey's fibers intensified the continuity between the periodontal ligament fiber and the alveolar bone and consisted of a buffer medium against stress. PMID- 7887127 TI - Morphometric analysis of the foot in adult Turkish men. AB - It is now well known that anthropometric measures of the foot differ in different communities. This research is a descriptive study to determine the foot measures collected from 1956 personnel working at a communication school. The results of this study are statistically different from the values of Paris system that is accepted by Turkish National Institute for Standardization (abbreviated as TSE). It is found that Turkish men's feet are shorter and wider as compared to the standards accepted by TSE. PMID- 7887128 TI - Effect of pregnancy on the prognosis for multiple sclerosis. A 5-year follow up investigation. AB - INTRODUCTION: The purpose of the study was to evaluate the effect of pregnancy and childbirth on the longterm prognosis for women with multiple sclerosis (MS). METHOD AND MATERIAL: A cohort of 39 women with definite MS were identified on 1.1.1986 using a reproducible selection method. The investigation was initiated in 1986 when handicap was evaluated by Kurtzke Disability Status Score (DSS). At a 5-year follow up 4 had died and 6 could not participate. There were 29 women in the investigation of whom 7 were childless, 10 had onset of MS at least 6 months after last childbirth, and 12 had onset of MS before or in connection with childbirth. Age and disease duration of the group was uniform. RESULT: At follow up the DSS significantly deteriorated (p = 0.008). The deterioration was seen particularly for childless women (p = 0.03) and women with onset of MS before or in connection with childbirth (p = 0.005). CONCLUSION: On the basis of this prospective investigation and the literature, it may be concluded that it is unlikely that pregnancy and childbirth have an influence on the longterm prognosis for MS. However, the conclusion must be interpreted with caution as the number of patients is small. PMID- 7887129 TI - Investigation of an epidemic of seasonal ataxia in Ikare, western Nigeria. AB - Seasonal outbreaks of an acute ataxic syndrome occur annually in parts of South Western Nigeria, characterized by cerebellar ataxia, nystagmus and varying levels of impaired consciousness following consumption of the roasted larvae of Anaphe venata Butler (Lepidoptera, Notodontidae). An investigation of an epidemic in Ikare, headquarters of the Akoko north-east local Government in Western Nigeria (pop. 60,000) in the 1993 disease season is reported. The diagnosis of seasonal ataxia was verified in 34 consecutive new admissions (M:F 1:3.25, median age 29 years, range 2-70 years). All were of low socio-economic status, and had consumed the larvae of Anaphe venata prior to the onset of disease. There were 1,126 admissions for the seasonal ataxic syndrome in Ikare in the 1993 season, with an estimated attack rate of 1.87%. The peak incidence was in August, when patients with the syndrome accounted for 71% of all hospital admissions. There was no mortality. Control measures included therapy with high-potency multivitamins and health education. PMID- 7887130 TI - Intracranial gliomas in Ferrara, Italy, 1976 to 1991. AB - INTRODUCTION: We planned a descriptive study on the incidence of intracranial gliomas spanning a 16-year period (1976-1991) in the Local Health Service 31 of Ferrara, Northern Italy. MATERIAL AND METHODS: We used a complete enumeration approach by reviewing all the possible sources of case collection available in the study area. RESULTS: The mean annual incidence rate was 5.8 new cases per 100,000 population (6.96 for men and 4.78 for women; p < 0.05), resulting in 4.7 per 100,000 when directly adjusted to the Italian population. The age-specific incidences showed a small peak in childhood, an increase with age, reaching a maximum in the age group 60 to 64 and then a decline in the elderly. This pattern is similar for both sexes. The adjusted rates increased from 3.94 per 100,000 population in the first five-year period to 5.6 per 100,000 in the third (a nonsignificant difference). The distribution of cases within the study area was substantially uniform. CONCLUSION: The incidence rates of Ferrara fell into the middle-high values so far reported and confirmed the male preponderance found in previous studies. The age-related pattern is similar to that observed, with few exceptions, in other surveys. Like other authors we did not find a significant temporal trend, although the incidence rates tended to increase with time. The data encourage further, wider epidemiological studies of a prospective nature. PMID- 7887131 TI - Immunogenetic heterogeneity and associated autoimmune disorders in myasthenia gravis: a population-based survey in the province of Ferrara, northern Italy. AB - INTRODUCTION: The well-established relationship between myasthenia gravis (MG) and HLA antigens varies among different ethnic groups. In Caucasians B8 and/or DR3 alleles have been found associated with young MG women without thymoma and with high titres of acetylcholine-receptor antibody (AChR Ab). An increased frequency of haplotype HLA-A3, B7 and/or DR2 has been observed in older MG patients with low AChR Ab levels. So far, there is no convincing evidence for an association between a specific haplotype HLA and ocular MG or MG with thymoma. MG subjects often show other concurrent autoimmune disorders suggesting a more general inherited predisposition to autoimmunity. We performed a community-based study to verify the HLA-A, B, C, DR and DQ profile on ethnically homogeneous MG patients and with the aim to estimate the frequency of concurrent autoimmune diseases and to compare HLA phenotypes to autoimmune status in different MG patients groups. METHODS: Forty-seven patients, living in the province of Ferrara, were followed-up in our neurologic department and typed for HLA Antigens. In addition a set of immunological laboratory tests was performed. RESULTS: We found a trend towards an increased B8 and DR3 frequencies in total affected population; an association between B8 allele and early onset of generalized MG sustained by thymic hyperplasia. The DR3 allele is statistically associated with the presence of additional autoimmune disorders. CONCLUSIONS: Our data support the hypothesis of a genetically-based heterogeneity of the disease and show an increased prevalence of associate autoimmune conditions in MG patients. PMID- 7887132 TI - Subarachnoid blood on CT and memory dysfunctions in aneurysmal subarachnoid hemorrhage. AB - Ninety patients with a previous subarachnoid haemorrhage (SAH) were given a set of memory tests comprising immediate free recall of words (indexing long-term memory, LTM, and short-term memory, STM), final free recall of words (indexing LTM), final cued recall of words (indexing LTM), and a digit span test (indexing working memory, WM). Patients with a large amount of blood on CT, carried out within 72 h of the bleed, showed LTM as well as STM dysfunction, whereas patients with a small amount of subarachnoid blood evidenced only STM dysfunction. Patients with the ruptured aneurysm located on the anterior cerebral artery, however, constituted an exception with dysfunction of both LTM and STM together with intact WM, independent of the amount of subarachnoid blood. Also, patients with internal carotid artery or middle cerebral artery aneurysms and large volume SAH displayed LTM dysfunction, but differed concerning STM, the former showing intact STM and the latter showing STM dysfunction. Thus, it appears, that the combined information from factors such as the amount of subarachnoid blood and the location of the ruptured aneurysm is of vital importance for explaining the different patterns of memory dysfunctions after SAH. PMID- 7887133 TI - Spinal arteriovenous malformations. Health-related quality of life after embolization. AB - The overall function, pain and mood disturbances of 19 patients with spinal arteriovenous malformations (AVM), treated by embolization between 1983 and 1988, were studied. The after-care had taken place in different hospitals and clinics. The patients demonstrated markedly poorer physical function (Sickness Impact Profile) and poorer psychological well-being (Mood Adjective Check List) than control population samples and a comparison group of traumatic incomplete paraplegics. The degree of decrease of mood levels implied possible depressive disorder (Hospital Anxiety and Depression scale) in 16% of the patients and differed from that of the paraplegic comparison group. Furthermore, the AVM patients reported more disturbance of their family and social life than the paraplegics and they were more seldom gainfully employed. Patients recorded a wide range of pain scores, significantly worse than the paraplegics, and their pain was closely linked to overall quality of life (QL) perception. The QL scores were consistently related to all measures of functional and emotional status, but no connection with neurological lesion levels or medical complications was found. Specialised programmes after embolization, such as those offered in spinal injury units, would appear appropriate for AVM patients to improve their physical functioning and to provide a more rewarding social life. PMID- 7887134 TI - Treatment of Parkinson's disease with NADH. AB - It has earlier been claimed that clinical improvement of patients with Parkinson's disease is obtained by treatment with NADH. This has to be verified by double-blind, clinical studies and measurement of biochemical effects of the treatment. In a double blind study five patients with clinically moderate Parkinson's disease were treated with NADH, 25 mg, given intravenously once a day for four days. Then they were given 25 mg NADH intramuscularly after 2 and 4 weeks. Disability scores were determined before each treatment and two weeks after the final injection. A control group (n = 4) with the same degree of Parkinson's disease obtained sodium chloride with the same schedule. According to the Unified Parkinson's Disease Rating Scale a tendency to clinical improvement was seen after the iv infusions in both treatment and placebo groups. However, the changes were not statistically significant, and no changes occurred during the following weeks. No changes were found neither in the study nor the control group regarding cerebrospinal fluid concentrations of dynorfin, metenkefalin, somatostatin, hydroxy-methoxy-phenylglycol, homovanillic acid and 5-hydroxyindole acetic acid. The results indicate that no great changes are obtained after short term treatment of parkinsonian patients with NADH, neither clinically nor biochemically. PMID- 7887135 TI - Magnetic motor evoked potentials (MEP) in diseases of the spinal cord. AB - Transcranial magnetic stimulation (TMS) is a non-invasive diagnostic method particularly suited to investigation of the long motor tracts. The clinical value of this method in many cortical and subcortical diseases has been well established, but comparable studies for most spinal cord diseases have still to be made. Forty patients in whom spinal cord disease was established by clinical examination, cerebrospinal fluid examination, and magnetic resonance imaging (MRI) were studied by means of somatosensory evoked potentials (SEP, median and tibial nerve stimulation) and magnetic motor evoked potentials (MEP, first dorsal interosseus and tibialis anterior muscle recordings after transcranial and spinal stimulation). The underlying pathology was neoplastic (n = 16), inflammatory (n = 15) or ischemic (n = 9). Clinical signs and symptoms ranged from slight sensory disturbances to complete paraplegia and had developed within minutes (ischemia) or over many years (benign neoplastic disease). The overall frequency of pathological SEP was slightly higher than that of MEP (78% vs 68%) which was statistically not significant (p > 0.05). This was also true for the subgroups, except for pure motor disorders, which gave the same yield for both methods. Decreased amplitudes or absence of MEP were more frequent in neoplastic than in inflammatory lesions (75% vs 33%, p < 0.05). In the latter, however, MEP more often occurred with increased latencies (40% vs 31%, p > 0.05, n.s.). Pathological SEP were found in 75% of patients presenting with pure motor abnormalities, while pathological MEP were found in 30% of patients with pure sensory disturbances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887136 TI - MELAS syndrome: correlation between clinical features and molecular genetic analysis. AB - The clinical manifestations and mitochondrial DNA (mtDNA) mutations in a Taiwanese family with a female proband exhibiting mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome are reported. Clinically, the proband had a stroke-like episode with right hemiparesis, hemianopsia and mental dysfunction as well as short stature, hearing impairments, and elevated lactate levels. Brain magnetic resonance images showed multiple increased signal intensities over the left frontal, parietal and temporal areas. There were no ragged-red fibers, but paracrystalline inclusion bodies were shown in the muscle biopsies under electron microscopic examination. A deficiency of NADH-CoQ reductase was also found in biochemical studies of the muscles. The family survey revealed no abnormal findings except for headache and episodic vomiting in her mother. The molecular analysis of mtDNA disclosed a mutation from A to G at the nucleotide pair 3243 of the mitochondrial transfer RNA(Leu) gene in the blood, hair follicles and/or muscle of the maternal relatives. A characteristic finding of the MELAS family is variation of percentage of mutated mtDNA in various tissues and individuals. However, a higher proportion of mutated mtDNA was noted in the proband than that in the asymptomatic or oligosymptomatic family members. From the data, the variable clinical phenotypes in this MELAS family can be explained at least partly, by the different proportions of mutant mtDNA in the target tissues of the proband and maternal relatives. PMID- 7887137 TI - Amnesia and vegetative abnormalities after irradiation treatment: a case study. AB - This paper describes a case of a patient (GX) with a brain tumour in the third ventricle who developed a syndrome of amnestic disorder and vegetative abnormalities (hyperphagia, oligodipsia) after irradiation treatment that followed brain surgery. The patient shows an extremely poor long-term memory on both visually and verbally presented material, and of autobiographical events occurring after the onset of the illness, but some preserved memory functions on short-term memory tasks, semantic memory tasks, and implicit memory tasks. Given the onset of symptoms only after irradiation (a memory deficit in particular), and the non-invasive nature of the surgery, the probable etiology is post irradiation syndrome. PMID- 7887138 TI - A 15-year follow-up of phenytoin-induced unilateral gingival hyperplasia: a case report. AB - INTRODUCTION-The aim of this case report is to present a 15-year follow-up of a patient with phenytoin (PHT) intoxication with unilateral gingival hyperplasia (GH). MATERIAL AND METHODS-A 50-year-old woman was followed-up for 15 years clinically and paraclinically after a heavy PHT intoxication. Her immunoglobulins in serum were checked on PHT and after 15 years treatment with carbamazepine. RESULTS-A gross mass of hyperplasia tissue found primarily in the left side of her mouth had disappeared and serum IgA which was subnormal at the first visit had normalized. CONCLUSION-It is possible to prevent GH from PHT treatment by intensive dental care, correct mouth hygiene and by change of treatment of carbamazepine. PMID- 7887139 TI - Hypokalemic periodic paralysis in association with tropical sprue: a case report. PMID- 7887140 TI - Anticardiolipin antibodies in MS patients. PMID- 7887141 TI - Swedish consensus on dementia diseases. AB - This consensus-based document on dementia diseases was worked out in 1988-1990 by Swedish dementia researchers. It comprises classification and nosology of dementia diseases taking into account brain-regional symptomatology and the pattern of degeneration. The significance of history-taking and 'bedside' examination is emphasized. Auxiliary diagnostic investigations are discussed, e.g. neuropsychological examination, brain imaging, and blood and cerebrospinal fluid analyses. PMID- 7887142 TI - The micromorphology in vivo of the buccocervical region of premolar teeth in young adults. A replica study by scanning electron microscopy. AB - The buccal surfaces of premolar teeth are common sites of gingival recession, generally attributed to overzealous oral hygiene. Scanning electron microscopy (SEM) of replicas made from dental impressions was applied to document the micromorphology of the buccocervical region of all premolar teeth in 27 dentally healthy, young adults. The SEM observations were correlated with clinical examination. Of the 216 sites, one-third, predominantly the maxillary first premolars, had gingival recession, but fewer than 50% were clinically discernible. The exposed roots were devoid of cementum, and the dentinal surface was smear-like or dotted with tubular apertures from which droplets of fluid extruded. SEM of replicas of gingiva, recorded as clinically healthy, frequently showed signs of inflammation: fluid exudate and distortion of gingival contour by swelling. The cervical enamel of healthy and affected sites showed characteristic periodic fissure-like cracks, probably enamel tufts. The high frequency of subclinical gingival recession, exposed cervical dentin, and gingival inflammation in dentally healthy young adults, in the absence of abrasion of hard or soft tissues, indicates the need to review conventional concepts of initiation of buccal recession and root exposure. PMID- 7887143 TI - Evaluation of the antimicrobial effects of sodium benzoate and dichlorobenzyl alcohol against dental plaque microorganisms. An in vitro study. AB - Evaluation of antimicrobial agents is based on in vivo and in vitro studies. The minimum inhibitory concentrations (MICs) of sodium benzoate and dichlorobenzyl alcohol to 115 strains of plaque microorganisms were determined by a broth dilution method. Sodium benzoate did not inhibit growth of any gram-positive cocci (MIC > 106,590 microM). MICs for Porphyromonas gingivalis and two strains of Treponema socranskii were 26,650 microM. The MIC of dichlorobenzyl alcohol to the reference strain of Actinobacillus actinomycetemcomitans was 723 microM and to P. gingivalis, two strains of T. socranskii, and Candida albicans 1,446 microM. MICs for other organisms were 2,892 to 5,784 microM. Saliva samples from 10 volunteers, collected at various times after toothbrushing with a dentifrice containing 10% sodium benzoate and 0.3% dichlorobenzyl alcohol, were analyzed gas chromatographically. Immediately after toothbrushing mean levels of sodium benzoate and dichlorobenzyl alcohol were 372,626 microM and 7,529 microM, respectively. After 5 min mean levels were 38,700 microM and 734 microM. In conclusion, the concentrations of both antimicrobials dropped rapidly during the first 30 min, but for 5-10 min they were high enough to inhibit growth of potential periodontal pathogens. PMID- 7887144 TI - Effects of a lactoperoxidase-system-containing toothpaste on dental plaque and whole saliva in vivo. AB - The effects of a lactoperoxidase-system-containing toothpaste. Biotene, on saliva and dental plaque were studied. In a double-blind crossover study 20 healthy volunteers used an experimental (comprising the complete peroxidase system) or a placebo (without lactoperoxidase, KSCN, and glucose oxidase) toothpaste twice daily for 2 weeks separated by a 2-week washout period. At base lines and at the end of both test periods saliva and plaque samples were collected, and plaque pH changes were monitored. Saliva was analyzed for hypothiocyanite (HOSCN/OSCN-) and thiocyanate (SCN-) concentrations and salivary peroxidase activity. The amount of total streptococci, mutans streptococci, lactobacilli, and total anaerobic flora was determined both in saliva and in plaque samples. The accumulation and the acidogenicity of plaque were also quantitated. A 2-week daily use of Biotene had no effect on salivary flow rate, peroxidase activity, HOSCN/OSCN-, SCN-, or any of the monitored bacterial counts compared with the placebo toothpaste. The accumulation of dental plaque was not affected by the lactoperoxidase-system containing toothpaste. The acidogenicity of plaque did not change significantly, nor did the two test dentifrices differ in their ability to inhibit the plaque pH drop caused by sucrose in subjects with normal salivary flow rate. PMID- 7887145 TI - Chemotaxonomy of Bacteroides: a review. AB - The loose definition of Bacteroides, some species of which are important etiologic agents of oral diseases, has enabled isolates with only marginal similarities to be reposited in this genus. Many attempts have been made over the years to improve the taxonomy of this heterogeneous group of bacteria. The present article reviews major chemotaxonomic characters and techniques that have been used for this purpose: pigmentation, metabolites, whole-cell fatty acids, phospholipids, isoprenoid quinones, carbohydrates of lipopolysaccharide, whole cell proteins, peptidoglycans, enzymes, pyrolysis mass spectrometry, DNA composition, restriction fragment length polymorphisms of DNA and ribosomal (r) RNA, homology of DNA and RNA, DNA-rRNA hybridization, and 16S and 5S rRNA oligonucleotide cataloging and sequencing. Despite improvements in their taxonomy, some bacteroides are still misclassified. Suggestions for further improvements in the taxonomy of bacteroides are made. PMID- 7887146 TI - A 6-year evaluation of a direct composite resin inlay/onlay system and glass ionomer cement-composite resin sandwich restorations. AB - The most undesirable characteristic of composite resin is its polymerization shrinkage. Two techniques developed to counter this problem are the composite inlay and the sandwich composite filling. The durability of 100 direct composite inlays and 34 closed and 16 open sandwich composite fillings made with a conventional glass ionomer cement were evaluated during a 6-year period in a group of low and high caries risk patients. Modified USPHS criteria were used. Six inlays (6%), 5 closed sandwich fillings (14.7%), and 12 open sandwich fillings (75%) needed replacement. Six other inlays and three closed sandwich fillings showed non-acceptable defects that could be repaired with composite resin. The direct composite inlays showed very good clinical durability, whereas the open sandwich filling with conventional glass ionomer cement as dentin replacement cannot be advocated as a class-II restoration. PMID- 7887147 TI - Dental caries and microbial and salivary conditions in Uruguayan children from two different socioeconomic areas. AB - Dental caries, microbial and salivary conditions, dietary habits, and socioeconomic conditions were studied in 100 12- to 13-year-old children from 2 different socioeconomic areas in Montevideo: Pocitos and Piedras Blancas. The residents of Pocitos had a higher educational level, better housing conditions, and occupations involving higher earnings than those of Piedras Blancas. The caries prevalence in the two areas was about the same, but the children in Piedras Blancas had more decayed surfaces and fewer filled surfaces than the children in Pocitos. The mean values for caries in Piedras Blancas and Pocitos were, DMFT, 4.2 and 4.2; DMFS, 8.1 and 7.8; DS, 4.7 and 2.5; and FS, 1.7 and 4.7, respectively. The differences in DS and FS were statistically significant. The frequency of sugar intake and the salivary secretion rate were similar, but the buffer capacity was significantly higher in Pocitos than in Piedras Blancas. The plaque index was the same, but the distribution of cariogenic microorganisms differed significantly. Fifty-eight per cent of the children in Piedras Blancas had more than 10(6) CFU of mutans streptococci per milliliter saliva, compared with 17% of the children in Pocitos. Similar differences were found with regard to the lactobacilli. The percentage of children with high numbers of mutans streptococci was higher in Piedras Blancas and lower in Pocitos than in previous epidemiologic studies in Scandinavia. It was, however, higher than that recently noted in Finland. PMID- 7887148 TI - Normal human contrast sensitivity for static and dynamic sinusoidal gratings. A comparison between two automated threshold determination designs. AB - Contrast thresholds for static and dynamic (phase-shifted at 2 rps) sinusoidal gratings were established for seven spatial frequencies 0.5-32 c/deg. An HP-85 desktop computer ran an automated stimulus descending algorithm. Subjects reported stimulus presence by pressing a switch. Two stimulus presentation designs were used. In method 1, the screen was blanked to mean luminance between presentations, while in method 2 the pattern remained unchanged until the next contrast level was presented. Mean thresholds were calculated from three successive threshold passages using 2 dB steps. Fifty-nine volunteers from a military unit, mean age 20 years, participated in the study. Method 1 always gave lower thresholds with less variability. For static gratings, this was statistically significant at 0.5 and 16 c/deg (p < 0.01 and 0.05, respectively) and for dynamic gratings at all spatial frequencies except 32 c/deg (p < 0.1 for 0.5 and 16 c/deg, p < 0.001 for 1-8 c/deg). An accuracy index was calculated from two determinations at 4 c/deg. Method 1 gave higher indices for both static and dynamic patterns, although not statistically significant. However, method 1 was significantly more time consuming. Method 1 was considered the more reliable of the two contrast threshold determining designs. PMID- 7887149 TI - Diffuse chronic retinal pigment epitheliopathy and exudative retinal detachment. AB - Two patients with bilateral chronic retinal pigment epitheliopathy are presented. Both patients had large areas of pigment epithelial decompensation and small pigment epithelial detachments at the posterior pole. In the macula subretinal fluid was scanty, but the first patient developed an extensive bullous retinal detachment with shifting of subretinal fluid with changes in posture in both eyes, the second patient had similar detachment in one eye. The etiology of the pigment epithelial disorder remained unknown. No inflammatory cells were found in the vitreous specimen or subretinal fluid in the first patient. Treatment with peroral corticosteroids alone or in combination with azathioprine and cyclosporin A, as well as surgery for retinal detachment in one eye, proved unsuccessful. Argon laser coagulation of the decompensated areas in the macula resulted in resorption of subretinal fluid and reattachment of the exudative detachment. PMID- 7887150 TI - Full-field electroretinograms in patients with central areolar choroidal dystrophy. AB - Patients with central areolar choroidal dystrophy are often difficult to diagnose because they are similar in fundus appearance to other retinal disorders. Nineteen patients with the diagnosis were studied in order to estimate the diagnostic and prognostic value of full-field electroretinography in this disorder. Our results showed that the cone b-wave amplitude in the ERG is decreased, that there is a progression in this decrease during a follow-up period of 5 years, and that the cone b-wave implicit time is prolonged. Central areolar choroidal dystrophy is considered to be primarily a choroidal disease. Our results indicate that it also affects most or all of the retinal cones. Further, our observations suggest that the disease is slowly progressive and that full field electroretinography is of value in its early diagnosis. PMID- 7887151 TI - Absence of foveal avascular zone demonstrated by laser scanning fluorescein angiography. AB - We present laser scanning fluorescein angiograms of abnormal foveal capillary patterns in a healthy subject and an insulin-dependent diabetic patient with mild diabetic retinopathy. In both subjects capillaries were seen to cross the central foveal area where capillaries are usually absent. The flow pattern of the foveal capillaries, which were visualised with the use of a laser scanning ophthalmoscope, was indistinguishable from that of the more peripheral capillaries, indicating that foveal vessels are functionally normal retinal capillaries. The two cases demonstrate that identification of abnormal capillary patterns induced by retinal disease such as diabetic retinopathy is made difficult by the marked interindividual variation in capillary anatomy. In prospective studies, however, the method may be capable of detecting subtle changes in early diabetic retinopathy with a high degree of sensitivity. PMID- 7887152 TI - Early changes in diabetic retinopathy: capillary loss and blood-retina barrier permeability in relation to metabolic control. AB - In diabetic retinopathy capillary loss and blood-retina barrier leakage are prominent factors. We present a study with quantitative measurements of both capillary loss and leakage and their relation to cumulative metabolic control. Seventeen insulin-dependent diabetic patients with no retinopathy or only mild background retinopathy and 10 years' duration of the disease were included in the study. Status of metabolic regulation had been followed for at least 6 years. Seven healthy subjects were included as controls. In diabetic patients the perifoveal intervascular areas were found to increase significantly with the cumulative HbA1c index (p = 0.02) and in relation to the presence of moderate background retinopathy (p < 0.02). The blood-retina barrier leakage and the area of the foveal avascular zone were not significantly different from healthy subjects and no correlation was found between the HbA1c index and blood-retina barrier permeability. We conclude that perifoveal capillary loss occurs early in the course of diabetic retinopathy and that this loss is related to prior glycemic control and to the ophthalmoscopic retinopathy level. PMID- 7887153 TI - Visual fields at different stages of diabetic retinopathy. AB - Available studies on visual field disturbances in diabetic retinopathy have shown conflicting results, obtained with different and often non-comparable techniques. We have studied visual fields at different stages of diabetic retinopathy with modern sensitive computerized technique taking precautions to limit disturbing effects of random field variation and lack of perimetric experience. Sixty-three diabetic patients, insulin-dependent and non-insulin dependent, were each subject to three test sessions using the 30-2 full threshold program of the Humphrey perimeter. Retinopathy levels ranged from 10 to 65 in the ETDRS Final scale. In eyes without retinopathy or with very mild and mild disease (levels 10-35) mean deviation values exceeding the p < 5% level occurred in only 4% of eyes in trained sessions, and the number of test points with significantly reduced sensitivity did not exceed that expected in normal eyes. In moderate and moderately severe diabetic retinopathy (level 43-47) and in severe non proliferative and proliferative retinopathy (levels 53-65) there was clear evidence of field loss, however, with significantly reduced mean deviation values in 44% of the eyes and 6.5% of tested points showing reproducible loss of sensitivity. Thus, there was no evidence of field loss in eyes with mild disease, but clear field defects in eyes with more advanced disease. Significantly reduced sensitivity was often correlated with retinal non-perfusion and there was seen a tendency towards more correlation in the midperiphery than paracentrally. PMID- 7887154 TI - The effect of panretinal laser photocoagulation on visual acuity, visual fields and on subjective visual impairment in preproliferative and early proliferative diabetic retinopathy. AB - The effect of panretinal laser scatter treatment on visual fields, visual acuity and subjective complaints was assessed in 11 patients with severe nonproliferative or early proliferative diabetic retinopathy. Patients were prospectively examined before and after panretinal treatment using automated static threshold perimetry with program 30-2 on the Humphrey perimeter, and they were interviewed. Visual field sensitivity was often depressed even before treatment with mean MD -4.3 (-1, -11.6) dB, but was significantly lower (p < 0.01, ANOVA) 2 weeks after treatment with mean MD -8.6 dB. Visual fields remained stable 4 months later. Treatment increased the number of eyes with visual fields as defined by abnormal MD values at the p < 0.05 level from 8 to 16 among the 17 treated. In spite of considerable impairment of visual fields after treatment, subjective problems were small and the visual field impairment seemed to have little influence on everyday life. PMID- 7887155 TI - Corneal sensation in insulin dependent and non-insulin dependent diabetics with proliferative retinopathy. AB - The corneal sensation of diabetic patients undergoing pan retinal photocoagulation for the treatment of proliferative retinopathy was measured using the Cochet-Bonnet aesthesiometer. Insulin dependent and non-insulin dependent diabetics both showed significantly decreased corneal sensitivity, and there was no significant change following pan-retinal photocoagulation. Insulin dependent diabetics with proliferative retinopathy had been diagnosed for a significantly longer period than non-insulin dependent diabetics, but had better corneal sensitivity than the latter group. Male patients were more likely to have brown irides, whereas there was a preponderance of blue irides amongst the females. Patients with blue irides also had significantly lower sensitivity than patients with brown irides. The results are discussed. PMID- 7887156 TI - Intraocular pressure in samples of elderly Finnish and Swedish men and women. AB - Intraocular pressure was measured in 231 systematically sampled 75-year-old men and women in Goteborg, Sweden and in 284 75-year-old and 201 80-year-old residents in Jyvaskyla, Finland as part of a comparative study on functional capacity and health, NORA 75 (Nordic Research on Ageing). After excluding the cases reporting glaucoma in their medical history or using drugs for glaucoma treatment there were no significant differences in the distributions of intraocular pressure between the men (mean intraocular pressure in the right eye 15.1 mmHg, left eye 15.0 mmHg) and women (mean intraocular pressure in the right eye 15.5 mmHg, left eye 15.8 mmHg) in Goteborg. In Jyvaskyla the 75-year-old men had significantly lower intraocular pressure (right eye 13.4 mmHg, left eye 14.2 mmHg) than either the Jyvaskyla women (right eye 15.1 mmHg, left eye 15.4 mmHg) or the men and women in Goteborg. Among the 80-year-olds in Jyvaskyla there were no significant differences between the sexes (means for the right eye 14.0 mmHg and 13.7 mmHg and for the left eye 13.9 mmHg and 13.7 mmHg for the men and the women, respectively). The 80-year-old women had lower intraocular pressure than the 75-year-old women of either location. Ouclar hypertension (intraocular pressure 22 mmHg or higher) was more common among the Swedish 75-year-olds than among either the Finnish 75- or 80-year-olds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887157 TI - The shape of the corneal apical zone after excimer photorefractive keratectomy. AB - Applying an experimental photo-keratoscope, which assesses the shape of cornea within the pupillary region, to a group of subjects who have undergone excimer laser photorefractive keratectomy over a central 4 mm chord diameter of the cornea, we report the shape of the typical cornea within the ablated zone conforms to a steepening ellipse (average shape factor, 1.25). A statistically significant difference in the mean shape factor (asphericity) between the photoablated and the normal cornea (average shape factor 0.89) was not confirmed. However, there is more variability in the shape factors found in the photorefractive keratectomy group compared with normals, within the same distance from the corneal apex. Using the criterion of overlap within two standard deviations, averaging the vertical horizontal meridians, 75% of photorefractive keratectomy eyes fall within the shape factor limits of the normal eye group. In all cases the post-ablated corneal surface was found to be regular in terms of surface quality alone. The excimer photorefractive keratectomy technique is therefore a clinically acceptable method of refractive surgery. PMID- 7887158 TI - Experimental myopia in chickens induced by corneal astigmatism. AB - Astigmatism has been suggested to be an important factor in the production and/or progression of myopia. Chickens have been used as a myopic animal model for several years. In the present investigation our aim was to evaluate the importance of surgically induced corneal astigmatism by peripheral corneal incision with compression suture in one eye, the right, of 3-day-old chicks. Vertical incision (2 mm) with compression suture (nylon 9-0, one stitch) induces against-the-rule astigmatism, horizontal incision with compression induces with the-rule astigmatism. Four groups were studied 1) with one vertical cut, 2) one horizontal cut, 3) two vertical cuts, 4) two horizontal cuts. The eyes were measured by caliper after 8 weeks. Eye enlargements were induced in all groups, however, less by one cut (astigmatism around 5 diopters) than by two cuts (astigmatism 10 diopters, or more). In the latter groups the pattern of equatorial eye enlargement depended on the axis of the induced astigmatism, the greater elongation being associated with the strongest refracting corneal meridian. All considered, the results suggest that significant corneal astigmatism could be another factor in the production of myopia, possibly acting by way of optical degradation of retinal image quality. PMID- 7887159 TI - Senile and presenile cataract. Survey of patients undergoing cataract surgery. AB - Two groups of patients operated on because of cataract were compared: 106 patients from Poland and 103 patients from Norway. Mean age in the Polish group was 60 years and in the Norwegian 76 years. To explain the difference in age at operation the incidence of some cataract risk factors--diabetes, myopia, rural residence, outdoor occupation, cataract in family, steroid therapy, smoking and alcohol intake--were evaluated. Significant differences between these two groups were found only for rural residence, alcohol intake and cigarette smoking. The author suggests another possible factor causing earlier cataract formation among Polish patients. PMID- 7887160 TI - Binocular inhibition of visual performance in patients with cataract. The influence of test reliability. AB - Patients with cataract may show binocular inhibition: their sight improves on closing the eye in which vision is poorer. Of 36 patients questioned, one-third reported this to be the case. To quantify this phenomenon, all patients undertook a battery of tests of spatial visual performance and, in an attempt to define the reliability of their scores, were tested on two separate occasions. Patients generally performed inconsistently: at best, of 8 patients who demonstrated inhibition on a single test, only 5 did so again when re-tested after a short interval. In general, the magnitude of inhibition was less than that which could be reliably detected using the test battery. In addition, self-reported inhibition was not predictive of inhibition measured psychophysically. It is concluded that clinical tests of form vision lack either the necessary reliability or sensitivity to identify patients with cataract who report inhibition of binocular visual function. PMID- 7887161 TI - The refractive error after implantation of a posterior chamber intraocular lens. The accuracy of IOL power calculation in a hospital practice. AB - The study included 188 patients, in which a posterior chamber intraocular lens was implanted after extracapsular cataract extraction. After modifications of the intraocular lens constants (SRK formula and SRK II formula) and correction of the axial length measurements (Colenbrander-Hoffer formula) had been made, the mean differences between the actual postoperative spherical equivalent and that predicted by the three formulas were -0.23D, -0.22D and -0.46D, respectively. More than +/-1.0D deviation from the predicted postoperative refraction occurred in about one-third of the cases. Inter-observed discrepancy regarding the accuracy of the preoperative measurement of the ocular axis length is suggested to be the main cause of unpredicted postoperative refractive errors. PMID- 7887162 TI - Long-term natural and modified course of surgically induced astigmatism after extracapsular cataract extraction. AB - A prospective study was carried out to investigate the long-term course of surgically induced astigmatism after extracapsular cataract extraction. Sixty-one eyes were followed for 36 months. In 27 eyes with post-operative astigmatism > 4D with-the-rule, one or two sutures were cut in the steeper meridian after 3 months. In another group of 34 eyes with only minor or no postoperative astigmatism with-the-rule, no suture was cut. We found that 1) postoperative astigmatism was significantly increased in all eyes after 1 week and 3 months, but decreased in time approaching preoperative values after 3 years, 2) surgically induced astigmatism was with-the-rule at 1 week and 3 months but turned against-the-rule in time in both groups. Astigmatism decay rate was significantly steeper in eyes with suture cutting, 3) the keratometric axis was exclusively with-the-rule after 1 week, but turned against-the-rule in both groups, approaching the preoperative distribution of axis after 3 years. We concluded that surgically induced astigmatism is a dynamic feature showing changes in size and axis even in the period 1-3 years postoperatively. Suture cutting seems to intensify the decrease in the induced astigmatism and accelerate the shift in astigmatic axis, turning astigmatism against-the-rule compared to eyes with intact sutures. PMID- 7887163 TI - The influence of age on characteristics of cataract patients. AB - The influence of age on 12 pre-, 1 intra-, and 2 postoperative patients' characteristics was investigated in 1261 consecutively performed extracapsular cataract extractions. The following characteristics were shown to be significantly associated with increasing age; cardiovascular disease (p < 0.0005), female gender (p < 0.0005), nuclear sclerosis (p < 0.0005), maculopathy (p < 0.0005), corneal guttate (p = 0.008) and reducing visual acuity in the fellow eye (p < 0.0005). Further, inadequate mydriasis at start of surgery was significantly associated with increasing age even after adjusting for glaucoma and pseudoexfoliation (p = 0.0007). After adjusting for pseudoexfoliation, a statistically significant relationship still existed between age and glaucoma (p = 0.0235). Even after controlling for relevant variables, i.e. maculopathy, a highly significant association was found between reducing visual acuity 4 months postoperatively and increasing age (p < 0.00005). Diabetes mellitus, the degree of cataract maturity, preoperative visual acuity of the operating eye, vitreous loss and postoperative inflammatory response were not significantly associated with increasing age. PMID- 7887164 TI - Preoperative ocular disinfection by the use of povidone-iodine 5%. AB - Numerous disinfective methods have been proposed in order to prevent intraocular infections during eye operations. In a clinical-laboratory study we evaluated the effectiveness of povidone-iodine solution 5% as a preventive - preoperative means of conjunctival antisepsis prior to ocular surgery. Conjunctival cultures were performed on 100 patients. Group A (50 patients) had their fornices washed with normal saline immediately before surgery. In Group B (50 patients) one drop of povidone-iodine solution 5% was applied prior to preoperative wash of the fornices with normal saline. Thirty-three out of 50 eyes from Group A had positive cultures (66%). Only 15 out of 50 eyes from Group B had positive cultures (30%). Bacteria flora differed in the two groups, with Group A exhibiting more dangerous strains. Preoperative-preventive disinfection with povidone-iodine 5% may prove to be advantageous to ocular surgery. PMID- 7887166 TI - Central retinal artery occlusion in a patient with Fabry's disease documented by scanning laser ophthalmoscopy. AB - Fabry's disease, angiokeratoma corporis diffusum, is an X-linked inborn error of glycosphingolipid metabolism due to lack of activity of the lysosomal enzyme, alpha-galactosidase A, resulting in progressive intracellular deposition of neutral glycosphingolipids in various tissues, including vascular endothelial - and smooth muscle cells. Occlusions of the retinal vessels are rare. We present a case of central retinal artery occlusion in a 25-year-old male with Fabry's disease, documented by fluorescein- and indocyanine green angiography performed by scanning laser opththalmoscopy. PMID- 7887165 TI - Local specific immunotherapy in allergic conjunctivitis. AB - We evaluated the effect of local specific immunotherapy in 40 patients suffering from seasonal allergic conjunctivitis. Twenty patients received saline solution in both eyes; and 20 others received local specific immunotherapy in both eyes. Sodium cromoglycate drops were instilled in both eyes in all patients. Subjective and objective symptoms, and cytological findings had significantly improved after 1 year in the group treated with local specific immunotherapy plus sodium cromoglycate compared to the group treated with sodium cromoglycate and saline solution. PMID- 7887167 TI - Retinal maculopathy possibly associated with amiodarone medication. AB - A report is given on a 59-year-old female who acquired a wet maculopathy in her only seeing eye during amiodarone therapy given for a cardiac disorder. After withdrawal of the drug and subsequent central retinal laser therapy her visual acuity stabilized at 0.7 (follow-up time 6 years). With no similar reports in literature, it is suggested that the association between amiodarone therapy and the central retinopathy was accidental only. PMID- 7887168 TI - Waardenburg's syndrome and pituitary tumor. AB - A 57-year-old woman with Waardenburg's syndrome presented with a 2-month history of decreased vision in the right eye. Computed tomography and magnetic resonance imaging studies for the brain disclosed a large suprasellar cystic lesion compressing the optic chiasm upwards. The association of Waardenburg's syndrome with pituitary tumor is rare, and may be fortuitous. However, it is interesting to note that both disorders are derived from the same embryological origin. PMID- 7887169 TI - The ANCA test in ocular inflammation. PMID- 7887170 TI - Semi-voluntary luxation of the globe. PMID- 7887171 TI - ATP and pH predictors of histologic damage following global cerebral ischemia in the rat. AB - In vivo changes of high energy phosphates and pH were determined with 31P NMR spectroscopy in rats subjected to symmetric or asymmetric partial global ischemia with reperfusion. Tissue damage was assessed by histology. ATP depletion, following PCr depletion, developed shortly after the onset of ischemia. In prolonged ischemia reperfusion was not followed with full recovery. APT depletion of more than 20% during reperfusion was associated with histologic damage; marked necrosis was associated with 50% reduction. Although during ischemia, severe persisting intracellular acidosis developed sometimes, and it was also associated with tissue damage, it did not appear to elicit tissue damage independently of the ATP depletion. Splitting of the Pi peak was useful in predicting heterogeneous distribution of the necrosis, thus it can reflect a heterogeneous distribution of the intracellular pH. PMID- 7887172 TI - Effect of increased depletion of copper, supplementary cholesterol diet and stress on the cholesterol concentration in wall of rat thoracic aorta. AB - The effects of experimental copper deficiency by itself, and in combination with other factor resulting in ischaemic heart diseases (IHD), were investigated on the lipid composition and copper status of serum and aortic wall in rat. The depletion of absorbed copper was raised by complex formation (D-penicillamine treatment). This provoked secondary copper deficiency was combined with a dietary cholesterol- and stress-loading. After treatment the levels of triglyceride (Tg), total cholesterol (Chol), HDL-cholesterol (HDL) (HDL = high density lipoprotein) and HDL2-cholesterol (HDL2) as well as copper (Cu) and zinc (Zn) in the serum and in aortic wall were measured by chemical analysis. It was pointed out, that increase in triglyceride and total cholesterol levels were promoted by the provoked copper deficiency in the serum and in the wall of the thoracic aorta. In combination with other risk factors it caused an increase in the elevation of Tg and Chol concentrations and has reduced the level of HDL2, significantly. PMID- 7887173 TI - Effects of ACTH 1-24 on hydrolysis of beta-casomorphin-4-nitroanilide in brain homogenates in vivo and in vitro. AB - Administration of ACTH 1-24 to 3-10 days old rats produced a significant decrease in hydrolysis of beta-casomorphin-4-nitroanilide (beta-CM-4NA) in the cytosolic fraction of brain homogenate in the first three hours after injection. Corticosterone treatment did not modify the hydrolysis of the substrate. ACTH 1 24 but not ACTH 4-10, Met-enkephalin or Leuenkephalin given to the brain homogenate resulted in a dose-dependent decrease in liberation of 4NA from beta CM-4NA. Kinetic data suggest competitive inhibition of ACTH molecule on hydrolysis of beta-CMA-4NA. The ACTH treatment, however, did not influence the hydrolysis of Pro-Gly-4NA or Pro-Pro-4NA in the brain homogenate in vitro. PMID- 7887174 TI - Further characterization of the 3-dimensional crystals of detergent-solubilized (Na+,K+)-ATPase from pig kidney. AB - Multilamellar 3-dimensional (Type I) crystals of detergent-solubilized, purified (Na+, K+)-ATPase enzyme of pig kidney grow in media consisting of 0.1 M KCl, 0.1 M NaCl, 20 mM imidazole pH: 7.5 (20 degrees C), 5 mM MgCl2, 5 mM DTT, 3 mM ZNaN3, 0.025 TIU/ml Aprotinin, 2 micrograms/ml BHT and 20-40% glycerol, using nonionic detergents of C12E8 or BRIJ 36 for solubilization. The refined crystallization protocol: the use of media containing 20% glycerol, the low detergent: protein ratio and preincubation at subzero temperature at the initial phase of crystallization resulted in a remarkable increase of the yield and overall dimension of the crystals (up to 3-4 microns), while the stacking of the crystalline sheets was dramatically reduced. Biochemical and structural analysis of these crystals revealed further similarities between the 3-d crystals of the (Na+, K+)-ATPase and the Ca2+ ATPase of skeletal muscle-SR (Taylor and Varga, J. Biol. Chem., 269, 10107-10111, 1994). Computer image processing of the electron micrographs of stacked crystalline sheets of (Na+,K+)-ATPase molecules gave unit cell dimensions: a = 166.2 +/- 3.8 A, b = 54.2 +/- 3.5 A, with an included angle of 90 degrees C. Based on the close identity of the filtered images in projection and of other data, we concluded that the 3-dimensional crystals of the (Na+, K+) ATPase contain only the alpha catalytic subunits. PMID- 7887175 TI - Enzymatic properties, metal composition and SH-group reactivity of the light and heavy sarcoplasmic reticulum vesicles. AB - Light (LT) and heavy (TTC) microsomes were isolated from the fragmented sarcoplasmic reticulum (FSR) of rabbit skeletal muscle by sucrose gradient centrifugation. The amount of the protein components (ATPase, "feet proteins", calsequestrine) showed substantial differences between the light and heavy fractions. The amounts of calcium, magnesium and zinc were about 2-4 times higher in the TTC fraction, then those of the LT fraction. The activities of the Ca2+ + Mg2+ activated para-nitrophenyl-phosphatase and acetylcholin-esterase were (about 1.5 times) also higher in the TTC fraction compared to the LT fraction. The ratio of the Ca-transport vs. ATP was 2.1 in case of the LT and 0.6 in case of the TTC fraction. The number of titerable SH-groups of the LT fraction, measured in EGTA medium containing Ca2+, was higher than those measured in the absence of Ca2+, while for the TTC fraction this number was higher when determined in the absence of Ca2+. We suppose that due to the higher amount of Ca2+ and Zn2+ in the TTC fraction those SH-groups which were present as Ca- or Zn-thiolates became titerable in EGTA-medium in the absence of Ca2+. PMID- 7887176 TI - Changes of organ blood flow and cardiac output after imidazole administration. AB - Effects of imidazole, an inhibitor of thromboxane synthesis (10 mg/kg bw., iv.) on the distribution of cardiac output and intrarenal hemodynamics were investigated in normovolemic (free water and salt uptake before the experiment) narcotized rats. The cardiac output was measured on the basis of the Stewart Hamilton principle, the blood flow of the organs by the Sapirstein method. 86Rb was used as indicator. One hour following the imidazole administration while mean arterial blood pressure remained constant a slight drop in the cardiac output (CO) was observed (CO-control: 24.1 +/- 4.77; CO-imidazole: 20.6 +/- 2.40 ml/min/100 g; p < 0.05) and total peripheral resistance increased (TPR-control: 42.3 +/- 9.27; TPR-imidazole: 48.3 +/- 7.05 R; p < 0.05). The vascular resistance in the heart, lungs (bronchial fraction), liver, spleen, intestine and adrenal glands remained unchanged. The blood flow of the skin and skeletal muscle decreased moderately, their vascular resistance increased following imidazole treatment. Inhibition of the thromboxane synthesis did not influence the renal and intrarenal (cortex and medulla) circulation, the percentile distribution of the intrarenal blood flow remained unchanged. The results suggest that TXA2 does not play a definite role in maintaining the a) vascular tone (blood flow) of different organs b) intrarenal hemodynamics (salt and water excretion) in normovolemic rats. PMID- 7887177 TI - Effects of benzpyrene and allylestrenol administered during pregnancy on the sexual behaviour of castrated and hormone treated adult rats. AB - Treatments with benzpyrene on the 15th, 17th and 19th day of the pregnancy result in sexually significantly less active offspring females following castration and treatments with sexual hormones in adulthood. The receptivity of animals treated with allylestrenol in embryonic period is also decreased but was not significant. Treatments with allylestrenol or benzpyrene of newborns did not alter the hormone induced sexual behaviour. Comparing with our previous experiments it seems that the effect of benzpyrene--which is structurally more distinct however it binds to the steroid receptor--is more pronounced on the sexual behaviour than allylestrenol. PMID- 7887178 TI - Glycosuric patterns in diabetes mellitus. AB - In one case of diabetes, normal glucose contents and volumes of the urine and high diabetic values alternate with each other. This periodicity may be of short duration (a couple of days), but long-lasting normal state can also occur. This state of aperiodicity may last almost a month. In such "smoothening" of hormone regulation, some modulator substances may play a role. PMID- 7887179 TI - Effect of malnourishment on intestinal glucose and fluid transport in rats. AB - Intestinal fluid and glucose transport in malnourished rats was investigated using the everted sac method on the small intestine. Malnourishment significantly (P < 0.001) reduced the serosal fluid transfer, mucosal fluid transfer, gut fluid uptake as well as gut glucose uptake. The results suggest that malnourishment affects the functional status of the small intestine. PMID- 7887180 TI - Pharmacological inhibition of brain carbonic anhydrase protects against 4 aminopyridine seizures. AB - The effects of the inhibition of carbonic anhydrase on the manifestation of tonic clonic seizures were investigated in freely-moving rats. 4-Aminopyridine, a specific blocker of the neuronal K+ channels was used to produce generalized convulsions. After pretreatment of adult male rats with 20 or 40 mg/kg acetazolamide, 3, 5, 7 or 9 mg/kg 4-aminopyridine was injected intraperitoneally and the latencies of the symptoms were measured. Pharmacological inhibition of brain carbonic anhydrase significantly increased the latency of onset of seizures. Bolus administration of acetazolamide decreased the incidence of generalized convulsions and protected against status epilepticus. Chronic acetazolamide treatment for 2 days affected only the generalized convulsions. The results suggested that alterations of the extracellular and intracellular pH by acetazolamide decreased the efficacy of synaptic transmission in several areas of the brain. The possible effects of the HCO3- ions on the sensitivity of synaptic and nonsynaptic neuronal receptors are discussed. PMID- 7887181 TI - Effects of MK-801 and ganglioside GM1 on postischemic prostanoid release and hippocampal lesion in gerbil brain. AB - In this study Mongolian gerbils were submitted to a normothermic bilateral carotid ligation lasting 5 min. A noncompetitive antagonist of NMDA receptors, MK 801, 0.8 mg/kg, was injected i.p. 30 min before ischemia, or the ganglioside GM1, 30 mg/kg, was given i.p. for 3 days, twice a day. The morphology of the hippocampal CA1 neurones and the brain content of cyclooxygenase metabolites of arachidonic acid: prostaglandin 6-keto PGF1 alpha and thromboxane Tx B2 were studied. Untreated ischemia induced the accumulation in brain of the 6-keto PGF1 alpha and Tx B2 immunoreactive materials, and resulted in a lesion of 70% of CA1 neurones. In the MK-801- and GM1-pretreated groups the postischemic levels of Tx B2 were significantly decreased. However MK-801 and GM1 did not prevent damage to the CA1 neurones in gerbils normothermic after ischemia, whereas a partial neuroprotection was observed in hypothermic, MK-801 treated gerbils. The results of this study indicate that NMDA receptors may participate in the mechanism of postischemic release of eicosanoids in brain. They also confirm a potential modulatory role of gangliosides. These results are discussed in terms of the involvement of cyclooxygenase metabolites of arachidonic acid in the mechanism of a selective delayed neuronal damage to the hippocampus CA1 after ischemia. PMID- 7887182 TI - Projection of visuotopically organized afferents to the dorsal thalamus in the opossum, Monodelphis domestica. AB - Retrogradely transported dyes, Fluorogold and Fast Blue were injected into both sides of the dorsal thalamus in the Monodelphis opossum. Projection of the presumed primary visual cortical area, superior colliculus and parabigeminal nucleus to the dorsal lateral geniculate nucleus and the lateral posterior- lateral intermedius nuclear complex were described. They show close similarities to the homologous projections in the North American Opossum, insectivores and some rodents. In comparison with rat, cortico-thalamic and tecto-thalamic projections in the Monodelphis are less numerous. The peculiarity of cytoarchtitectonics of cortical layer 6 is described and discussed. PMID- 7887183 TI - Spatial summation processes in visually driven neurones of cat's pretectal region. AB - The spatial summation processes of single neurones of cat's pretectal region were investigated with moving and stationary visual stimuli. The results indicate that the majority of the investigated neurones changed their responses essentially at the gradual increase of size of the applied stimuli (i.e. showed negative or positive summation). Particularly, direction non-sensitive neurones showed symmetrical changes of spatial summation curves in response to two opposite directions of movement. By contrast, in some direction sensitive neurones different characteristics of responses for the two opposite directions of movement were observed. Thus the number of discharges in the responses to the preferred direction could increase or decrease at the gradual increase of the moving stimulus size, while the responses to the null direction could remain stable or vice versa. The same was observed for the "ON" and "OFF" responses in the ON-OFF neurones. Thus, it appears that the pattern of responses of a given neurone to different directions of movement and to the "on" and "off" periods of stationary stimulation are shaped by independent mechanisms. PMID- 7887184 TI - Two neuronal systems involved in short-term spatial memory in monkeys. AB - The investigation of the neuronal activity in the monkey cerebral cortex during the delayed spatial choice performance allowed us to develop the hypothesis about two neuronal networks supporting the operative memory. The work of one of them is based on the relay-race and reverberation principles of information transfer. Another neuronal network provides for the reliability of transfer phases of these processes. The two networks are present in both prefrontal and parietal association cortical area. PMID- 7887185 TI - Short term changes of cortical body maps following partial vibrissectomy in adult mice. AB - Vibrissae-to-barrels pathway is often used as a model for investigating CNS plasticity. We examined early changes in the cortical representation of row C of vibrissae in adult mice, following vibrissectomy removing all whiskers except row C. The changes of cortical representation of the spared row of vibrissae were mapped with 2-deoxyglucose autoradiography. We found that one day after lesion of vibrissal follicles the areal extent of cortical representation of row C is smaller than normally, but 7 days post lesion it increases significantly, by 60 to 90%, in all cortical layers. Additionally, seven days post-lesion the intensity of labelling was increased in cortical layer V. The result suggest that plasticity that can be observed with 2-deoxyglucose mapping in the barrel cortex is not due to unmasking of existing connection, but to reorganization of connectivity at many levels. PMID- 7887186 TI - Behaviour-related effects of physostigmine on the rat visual evoked potential. AB - The present study compares behaviour-dependent and physostigmine-induced changes of the visual evoked potential (VEP) in unrestrained rats to provide further indications on the role of acetylcholine in the behavioural VEP modulation. On 30 rats the VEPs on the pial surface of the primary visual cortex were investigated during five spontaneous behavioural states. Physostigmine, carbachol and nicotine were intraperitoneally applied on 7 rats. Several VEP parameters were found changing in dependence of the arousal level: the VEP latency, the amplitude of the second negative component (N41), and the voltage of the positive component between 60 and 80 ms after the light flash. Physostigmine caused amplitude alterations like during high arousal states. The VEP latency, however, was altered in an opposite way. Nicotine specifically altered the N41 amplitude whereas carbachol delayed the latency of the VEP. The second negative component (N41) is assumed cholinergically modulated. Moreover, the negative component between 60 and 80 ms latency that emerged in high arousal states may be cholinergically generated and may represent a marker of the activation degree of the cholinergic system. PMID- 7887188 TI - Cholinergic manipulations and passive avoidance in the rat: effects on acquisition and recall. AB - A review of the literature concerning cholinergic manipulations and passive avoidance reveals that state-dependency is usually not controlled adequately, nor is acquisition of the passive avoidance task ascertained before retention is tested. These problems make interpretation of results difficult. We report three experiments on 129 rats, controlling both of these factors, in which scopolamine and pilocarpine impaired both acquisition and retention of a passive avoidance response. Lesions of the nucleus basalis magnocellularis had no effect on this task. The results suggest that an optimal level of central cholinergic activity exists for learning and memory, and that deviations from this optimal level impair acquisition and retention. PMID- 7887187 TI - Cortical area in the rat that mediates visual pattern discrimination. AB - In Experiment I, bilateral ablations of the caudolateral cortex involving Krieg's area 36 impaired discrimination of visual patterns but not delayed alternation. In Experiment II, the same type of lesions retarded postoperative learning to discriminate embedded visual patterns. In rats from the Experiment II tracers of axonal transport gave no signs of damage of the connections of the primary visual cortex. In agreement with this, Nissl stain of the dorsal lateral geniculate nuclei showed no neuronal loss or gliosis. These results suggest that caudo lateral cortex in rats corresponds to the inferotemporal cortex of primates. PMID- 7887189 TI - Memory impairment in patients with stereotaxic lesions to the hippocampus and amygdala. AB - The study aimed at testing: (1) whether stereotaxic damage to the hippocampus and amygdala results in a memory deficit, (2) whether the memory functions subserved by the hippocampus are lateralized and (3) whether time limited storage of sensory information is impaired after focal hippocampal and amygdalar lesions. Seven patients with unilateral stereotaxic damage to the anterior part of hippocampus and unilateral or bilateral damage to the medial part of amygdala and 11 control subjects with no brain damage participated in the research. They were presented with memory tests that required either remembering a spatial arrangement of simultaneously presented verbal vs nonverbal stimuli or a temporal order of sequentially presented items. Moreover, a sensory information storage test was used. The results indicate that even small damage limited to the anterior part of the hippocampus and medial part of the amygdala results in a mild memory deficit. Memory impairment was not related to the side of hippocampal lesion. This suggests that memory function subserved by the hippocampus is not lateralized. Differential effects of left and right lobectomies found in previous studies were, thus, probably due to the damage to temporal cortex. The results showed, however, that sensory information storage limited to 3 s is not impaired after focal damage to the hippocampus and amygdala. A clear lateralization effect showing right hemisphere advantage in that function was found. PMID- 7887190 TI - The contralateral impairment of the orienting ocular-following reflex after lesions of the lateral suprasylvian cortex in cats. AB - The cortex of the middle suprasylvian sulcus was removed unilaterally in cats with brain stem transected at the pretrigeminal level. The vertical following reflex was evoked by a slit of light (1 degree x 4 degrees) moving along the vertical meridian or parallel to it up to 40 degrees in the left or right hemifield. The reflexes from the contralateral hemified were greatly reduced. This contrasts with previous reports with perimetry test where authors made smaller lesions. PMID- 7887191 TI - Effect of alpha-tocopherol, pyridoxine and dexpanthenol on the stress in crease of nonesterified fatty acids levels in the brain. AB - The supposed antistress effect of vitamins-alpha-tocopherol, pyridoxine and dexpanthenol (pantothenic acid precursor)--was followed on the model of nociceptive stress in laboratory rats. The decrease of the stress enhancement of nonesterified fatty acids (NEFA), estimated in the brain cortex, hypothalamus and the brain stem, was taken for the indicator of the antistress effect. Nonesterified fatty acids were determined with the help of gas chromatography following the separation performed by thin layer chromatographic method. Five-day application of alpha-tocopherol acetate (per os, 300 mg.kg-1) led to a decrease of the stress enhancement of arachidonic acid level in the brain stem. PMID- 7887192 TI - Oral test of magnesium tolerance. AB - Author presents original methodics of oral Mg deficiency testing, suitable for the detection of Mg deficiency, namely the latent states which could not have been easily evidenced till now. The test follows the retention of per os applied preparation of Mg on the basis of its discharge in urine. The realization of the oral Mg tolerance test is neither complicated nor embarrassing for the patient, it is thus applicable even in the out-patient practice. PMID- 7887193 TI - Evaluation of the validity of human papillomavirus detection in paraffin-embedded cervical samples by the DNA hybridization in situ. AB - The DNA probes for HPV types 6, 11, 16, 18, 33 and 56 were prepared and biotinylated. They were used in hybridization in situ test for detection HPVs in the cells of 29 cervical samples with various grade of dysplasia and CIS. It was verified that DNA probes are suitable for HPV detection and that the grade of pathological changes is dependent on the presence of viral DNA. On the other hand, the pathological diagnosis of koilocytosis often do not reflect actual presence of HPV DNA in cell genome. PMID- 7887194 TI - Intrabronchial brachytherapy using 226-radium source. AB - Present work reports on results of manual brachytherapy in lung cancer using intrabronchial catheter and 226-radium source. Expected dosage was 18 Gy at 1 cm from the source. This therapy was combined with external radiotherapy by 60 cobalt till the dosage about 65 Gy. 19 men were treated, the mean survival was 14.3 months. Advantages and disadvantages of the method are discussed. PMID- 7887195 TI - [Hypothyroidism and serum lipids]. PMID- 7887196 TI - Axillary venous thrombosis (Paget-Schroetter syndrome): possible therapy by low molecular weight heparin. AB - The authors report on a patient with spontaneous thrombosis of the right axillary vein (Paget-Schroetter syndrome). The treatment with low-molecular weight heparin was successful and no complications were observed. PMID- 7887197 TI - Neurotransplantation--a new method of treatment in psychiatry? AB - The authors present the results of their catamnestic evaluation of the first few patients (diagnosis of schizophreny; atrophic process posttraumatic and Alzheimer's dementia), in whom implantation of neuronal embryonal tissue into the brain was performed in the last few years. They warn against excessive publicity and optimistic appraisal by neurosurgeons because psychiatric examinations after some time fail to confirm the success of the operation. PMID- 7887198 TI - Advanced EMG techniques in diagnostics of spinal muscular atrophies and motor neuron disease--magnetic stimulation, single fiber EMG and macro EMG. AB - Motor neuron disease (MND) and spinal muscular atrophies (SMA) are difficult to diagnose with classical EMG methods because significant findings appear relatively late and both groups of diseases show neurogenic type of record differing only in a relatively greater amount of fasciculations and higher amplitude of motor unit potential (MUP) in MND compared with SMA. We examined 12 patients with MND-amyotrophic lateral sclerosis and 7 patients with SMA type III and IV according to Swash with advanced EMG techniques-magnetic stimulation, single fiber and macro EMG. With transcranial magnetic stimulation, a significant prolongation of cortical latency was found in MND (P < 0.0001 right hand and P < 0.0005 left hand) against SMA, where it was almost normal. With single fiber EMG, mean jitter was less markedly increased in MND (P < 0.05 against SMA) and fiber density was lower in MND (P < 0.005). With macro EMG, no significant difference was found in either macro amplitude or area. Macro fiber density was also lower in MND (P < 0.005). Advanced EMG techniques proved to differentiate clearly the III. (Kugelberg-Welander) and IV. (adult) type of SMA from MND-amyotrophic lateral sclerosis. PMID- 7887199 TI - Application of Corynebacterium parvum lysate into the brain of rats- morphological study. AB - The authors investigated the influence of application of the Corynebacterium parvum lysate (CPL) into the brain of rats with aim to define the resulting morphological changes. Variable amount of the CPL (0.1, 0.35, 0.7 mg) was injected under stereotactic control into frontal lobe of the left cerebral hemisphere. Morphological changes were studied after intervals of 3, 7, 14, and 30 days respectively. CPL lead to inflammatory and reparative changes in direct relations to the administered dosage. The most pronounced reaction was observed on days 3 and 7. Morphological changes were still visible on day 14. There were no valid difference between the application of efficient CPL and the control physiological saline solution (PSS) after thirty days. The authors suggested that CPL is likely to be safe also in human malignant brain tumor therapy. PMID- 7887200 TI - Local application of antibiotics in treatment of cerebral abscess. AB - The authors evaluate 61 patients treated for cerebral abscess. These patients were divided into 2 groups. The first group consisted of 42 patients who had the cavity left after the removal of the abscess irrigated with an antibiotic during the surgery. The other group of 19 patients were treated without this antibiotics. Only 2 patients of the first group (i.e. 4.7%) died as against the 6 deaths (i.e. 31.5%) in the other group. This result indicates the beneficial effect local administration of antibiotics has in treating cerebral abscess. This observation should however be checked on a larger series of patients. PMID- 7887201 TI - Some reflections about portosystemic shunt in portal hypertension. AB - The authors report on the group of 85 patients with portal hypertension in whom a portosystemic shunt was established for uncontrolled bleeding from varices--in the period from 1968 to 1993. A total lethality was 9.4%, in planned operations 5.9%, in acute interventions 22%. Some aspects of shunt-operation are discussed (prehepatic portal hypertension, acute shunt, shunt preceding liver transplantation). It is concluded that the portosystemic shunt still plays a role in the therapy of complicated portal hypertension, although only as a selective intervention. PMID- 7887202 TI - Changes in colchicine and demecolcine content during vegetation period of colchicum autumnale L. AB - Colchicine and demecolcine were determined in raw and dried leaves, stems, mother and daughter corms of Colchicum autumnale L. in four stages of its ontogenesis. The colchicine content in raw material varies during plant growth. The content of both alkaloids decreases with drying. The HPLC method used is suitable both for the phytochemical analysis of Colchicum and for the toxicological evaluation in cases of intoxication by these plants. PMID- 7887203 TI - Analgesia after intercostal thoracotomy. AB - At present, several possibilities of postoperative analgesia have been known in the case of thoracotomy. Most frequent is the bolus administration of various analgetic drugs, continuous analgetic infusions, or, now more preferred the epidural application of analgetic drugs. The authors compared two groups of patients subjected to intrathoracic surgery and hospitalized at the Ist Surgical Clinic in Olomouc. The first group (23 patients) was given analgetics by the classical method (bolus administration), to the second group (15 patients) epidural morphine was applied. No significant differences were found between the both groups. Postoperative complications (e.g. atelectasis) did not occur in any group of patients, values of blood gas according to Astrup were within normal limits. The day of the operation was subjectively better tolerated in the second group but there were some insignificant complications related to morphine administration (vomiting, urine retention) even in 60% of cases. PMID- 7887204 TI - Biochemical aspects of immunomodulation by Propionibacterium acnes. AB - The present paper deals with the effect of indomethacin and/or Propionibacterium acnes (Pa) on the cytochrome P-450 content in liver microsomal fraction, free fatty acids and lipase concentration in serum with respect to the phagocytic activities of monocytomacrophage system, changes in weight of the spleen and liver, survival after LD100 of Klebsiella pneumoniae, and histology of the spleen and liver. The results obtained indicate that INDO acts as an inhibitor of cytochrome P-450 and at the same time stimulates functions of the monocytomacrophage system in all the parameters studied. Pa, a classical immunomodulator, inhibits cytochrome P-450. After the initial suppression phase (3rd day after administration), it stimulates significantly the activity of monocytomacrophage system and increases the amount of FFA in the serum. The combination of both preparations also inhibits the cytochrome P-450 concentration in the liver and stimulates functions of the monocytomacrophage system in all the studied parameters. However, no temporary suppression of phagocytic activities was observed on the 3rd day of the experiment, in contrast to the animals administered Pa alone. Serum FFA concentration increased significantly. The application of both preparations accelerated markedly the onset of proliferation and differentiation processes in lymphatic follicles of the spleen. PMID- 7887205 TI - [Liaison programs in drug abuse-AIDS]. AB - AIDS has acquired a growing importance for psychiatry because of the number of infected people and the increasing attention that these patients need. The major risk group in Spain is the drug users one. These patients share management problems when they are in general hospitals settings, both for their psychiatric aspects and for the consequences of drug abusing. A consultation liaison psychiatry service system improves the attention to these patients and reduces the emergency interventions and the hostility against the staff. The consultation liaison psychiatry system has generated an overall improvement in our hospital to fulfil the patients need and the relations and atmosphere among the therapeutic team. PMID- 7887207 TI - [Contribution to a systemic interpretation of anorexia nervosa]. AB - The different ways in which anorexia nervosa has been understood throughout history are briefly described. Reference is made to those investigations underlining the role of the family in its pathogenesis, mainly to the papers on this subject that the authors themselves have published in the decade of the 70s. Then, an attempt of a systemic interpretation of anorectic syndrome is made, starting from the assumption that this acquires specific interactional characteristics in and for the family system in which uit has emerged. The more specific goals of this paper would be: to accurately describe the interaction forms of the system and sub-systems of anorexia nervosa; to put in evidence the function of the fundamental symptom, starvation; and finally, to make an approach to an eventual therapeutic intervention on the "anorectic" system. PMID- 7887206 TI - [Impulsive behaviors in opiate-dependent subjects treated with naltrexone]. AB - Thirty three heroin dependents (DSM-III-R) attending a naltrexone clinic were assessed to see if their histories of bulimic and non-suicidal self-aggressive behaviours would allow to predict the therapeutic response of the opioid antagonist. Neither these impulsive behaviours non previous suicide attempts or over-doses could predict such a response, which was evaluated according to the time spent under treatment with naltrexone. Before the administration of naltrexone, one or more of the studied impulsive conducts were detected in 87.8% of the sample (n = 29). None of the patients combined enough criteria to be diagnosed of bulimia (DSM-III-R). In 32 patients the occurrence of changes in the impulsive behaviours studied during the treatment period with the opioid antagonist were determined. These variations were not related to the determinations of abuse drugs in urine or with intake of psychoactive drugs. During the treatment with naltrexone, 15 patients ceased to present self-injuries without suicidal purposes and none of the patients began these behaviours for the first time. However, some patients without a previous history of bulimic behaviour developed this condition during the administration of the opioid antagonist. In this sense, four subgroups of patients can be differentiated according to the moment in which the bulimic behaviour appeared: subgroup A includes 7 individuals (21.7%) who discontinued this behaviour upon receiving the antagonist, while subgroup B (n = 3; 9.3%) is made up of those who presented this behaviour during both heroin consumption and the administration of naltrexone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887208 TI - [Anxiety, depression, stress in "depersonalization" and "derealization"]. AB - We quote the terms "depersonalization" and "derealization" though meaningless in an absolute sens, and feel it is suitable to define them as: "The diminishing of the feeling of significance experiences (vivencia) of the ego and of the reality". Theme of the communication: twofold: Remember a frequent omission--with important exceptions--is a lack of focus on the terrible pathos which acquires a certain intensity this syndrome. I have working in this direction since 1960 and specifically since 1988 with a total of 3.592 patients affective and obsessive compulsive, from which I selected 242, with "depersonalization" and "derealization" syndromes. 60 of them clinically severe. As assessed by the clinical phenomenological method. The observation time varied from three months and aigth and half years. "Under the auspices of egodistonia with a correct judgement of reality" in following areas: Environmentally (speak of "symptom of Tantalus"...). In the diminishing of sense of body. The patient involuntary memory. In the area of thought. In the area of the perception of time. Independent of those other stress situation which are known to a accompany the appearance of the syndrome of the "depersonalization" and "derealization" we think that this may produce at times symptoms of post-traumatic stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887209 TI - [Suicide and euthanasia as attitudes of desire facing death]. AB - Death can come by different ways and in a many circumstances, some naturally and other accidentally. This research will analyse two death's manner with special characteristics: those that people cause themselves conscious and deliberately: Suicide and Euthanasia. It describe different types of this two manners of death, and some of the principal theories about this matter, analysing attitudes propers and impropers face these different death's manners. PMID- 7887210 TI - [Allergic illnesses and psychiatric disorders]. AB - In the Allergic Service of a General Hospital 56 allergic patients were studied. They were patients with hypersentivity to drugs, allergic rhinitis and asthma who presented different psychological disorders. They were assessed with different variables: previous psychiatric diagnosis, personal and familiar background of psychiatrics disorders, the most frequent allergic disease, and the sociodemographic variables. Allergic to Drugs patients are identified like the ones who presents the highest number of psychological disorders. From the point of view of the sociodemographics aspects the characteristics of the allergic patients that receive psychological attendance correspond to: women of ages between 30 and 50 years old with Elementary Education and whose occupation is housewife. As common psychological character to this groups of patients is identified the presence of expressed anxiety in different ways, depending on the different variables. PMID- 7887211 TI - [Silva's Method of mental control and changes in the EEG alpha rhythm]. AB - Electroencephalographic recording was performed in 11 patients graded by the Silva's Method under basal conditions and under "dynamic meditation". Previous papers showed changes in the EEG of subjects who practice diverse methods of meditation and relaxation. Our results reveal a significant increase in the mean values of the alpha potency in occipital -01, 02- and temporal--T3, T4--areas, while subjects were practicing dynamic meditation. PMID- 7887212 TI - [Sauvages and nosological diagnosis in psychiatry]. PMID- 7887214 TI - Proceedings of the 4th International Conference on Hemochromatosis and Clinical Problems in Iron Metabolism, and the 11th International Conference on Iron and Iron Proteins. Jerusalem, Israel, April 27-30, 1993 and May 2-7, 1993. PMID- 7887215 TI - The structure and function of iron regulatory factor. PMID- 7887213 TI - Mechanism of Fe(II) oxidation and core formation in ferritin. PMID- 7887217 TI - Translational control by iron-responsive elements. PMID- 7887216 TI - Structure and function of IREs, the noncoding mRNA sequences regulating synthesis of ferritin, transferrin receptor and (erythroid) 5-aminolevulinate synthase. AB - The synthesis of least three proteins involved in iron metabolism is coordinately regulated in animals through noncoding sequences in mRNA, the IREs; the transcription of the genes encoding the proteins are also regulated. Cellular iron is the best known effector of changes in regulation of mRNA with IREs. A hairpin loop is the secondary structure of IRES which conserve the hairpin loop sequence, CAGUGU/C. However, variable stem sequences, apparently related to mRNA specific function, create a family of IRE regulatory sequences. At least three types of proteins recognize IRE regions: (1) Nucleases which degrade mRNAs with 3' noncoding IRES; the IRE/IRE-BP stabilizes mRNAs with 3' noncoding IRES (transferrin receptor mRNA). (2) Initiation factors/ribosomes; the IRE/IRE-BP blocks ribosome binding of mRNAs with 5' noncoding IREs (ferritin, eALAS mRNAs). (3) Initiation factors to enhance translation (ferritin mRNA) when the IRE-BP does not bind; the ferritin IRE is thus both a negative and positive control element depending on which type of protein is bound. The IRE in ferritin mRNA is the most studied IRE to date. Site-directed mutagenesis shows that sites throughout the IRE alter negative control and IRE-BP binding reflecting the fact that the footprint of the IRE-BP is over the entire IRE. Base paired flanking regions (FL) which are ferritin IRE specific, enhance the effects of IRE-BP binding on negative control. Positive control is altered by modifying the single sites in stem/internal loop but not in the hairpin loop.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887218 TI - Chemico-physical and functional differences between H and L chains of human ferritin. PMID- 7887219 TI - A new look at ferritin metabolism. PMID- 7887220 TI - Bacterioferritin: a hemoprotein member of the ferritin family. PMID- 7887221 TI - Intracellular iron. PMID- 7887222 TI - Distinct features of iron metabolism in erythroid cells: implications for heme synthesis regulation. PMID- 7887223 TI - Cellular ferritin uptake: a highly regulated pathway for iron assimilation in human erythroid precursor cells. PMID- 7887224 TI - Differential effects of iron and iron carrier on hematopoietic cells differentiation and human ADA gene transfer. AB - The role of iron and heme was examined in bone marrow cells from iron-deficient and chronically iron-overloaded rats. Erythroid colony cultures (CFU-E) demonstrated that iron-overloaded bone marrow cells were poor hemin (iron carrier) and CFU-E responders in vitro, whereas iron-deficient marrows grew exuberant numbers of CFU-E and responded to hemin. Results support the concept that iron, or associated factors, plays an important role in the manipulation of HO activity which modulates the hemopoietic potential of the organism. Using cultures of erythroid (CFU-E, BFU-E) and myeloid (CFU-GM), results demonstrated that exogenous hemin (iron carrier) has a specific beneficial effect on human bone marrow progenitor cells, which is not seen with iron (10(-4)M) or other metalloporphyrins. Higher concentrations of iron (10(-3)M) and ZnPP were in fact inhibitory to bone marrow growth. This inhibition was not reversed with higher concentrations of Epo or GM-CSF. The beneficial effect of iron may be best realized in the bound form such as heme. In addition, the effect of bound and nonbound iron was tested for its effect on gene transfer. By using a murine adherent cell layer (ACL) in a prestimulation phase, followed by human gene transfer of ADA into mouse bone marrow cells and Southern blot analysis, successful gene transfer was accomplished. ADA integration patterns were detected in CFU-S from stem cells of mice 5-11 months after transfer. When 10 microM ferric chloride was included in the ACL prestimulation phase, there was a marked depression in ADA integration into stem cells as compared to heme or non-heme controls. Furthermore, heme-bound iron had no effect and deferoxamine included with iron was able to reverse the inhibitory effect of iron on the gene transfer process. Thus, iron must be non-bound to exert its suppressive effect, and chelation of excess iron under clinical conditions of iron overload may be essential for successive gene transfer. PMID- 7887225 TI - A hemin-inducible enhancer lies 4.5 Kb upstream of the mouse ferritin H subunit gene. PMID- 7887226 TI - Iron deficiency: the global perspective. AB - The prevelance of IDA in industrialized countries has declined in recent decades, but there has been little change in the worldwide prevalence. IDA is currently estimated to affect more than 500 million people. Recent studies have indicated that anemia per se, the most common manifestation of iron deficiency, is less important from a public health standpoint than liabilities associated with tissue iron deficiency. The most important of the latter are an impairment in psychomotor development and cognitive function in infants and preschoolers, a deficit in work performance in adults, and an increase in the frequency of low birth weight, prematurity, and perinatal mortality in pregnancy. There have been several recent advances in combatting nutritional iron deficiency. One of the major problems has been in distinguishing iron deficiency from other causes of anemia seen epidemiologically such as malaria, HIV infection, chronic inflammation, hemoglobinopathies, and protein energy malnutrition. When combined with serum ferritin and hemoglobin determinations, the serum transferrin receptor assay is a valuable addition in epidemiologic surveys because it provides a quantitative measure of functional iron deficiency and it distinguishes true IDA from the anemia of chronic disease. The most difficult challenge is to develop effective methods of supplying iron to large segments of a population. Supplementation with iron tablets is suitable for only brief periods of need such as during pregnancy. The poor compliance with existing supplementation programs is believed to be due mainly to the gastrointestinal side effects of oral iron which can be eliminated by the use of a gastric delivery system. The most effective long-term strategy is to increase the intake of bioavailable iron in the diet. The customary approach has been to fortify a food staple such as wheat, rice, sugar, or salt, and thereby increase the iron intake of the entire population. However, because of concerns about the risk of cancer and heart disease in individuals with high iron stores, there is an increasing reluctance to supply iron to individuals who do not require it. A more effective strategy is to fortify food vehicles that are targeted to segments of the population at greatest risk of iron deficiency such as infants and school children. Because of the strong inhibitory properties of diets in regions of the world where iron deficiency is most prevalent, the use of NaFeEDTA has important advantages for food fortification. PMID- 7887227 TI - Iron regulation in the brain at the cell and molecular level. PMID- 7887228 TI - Iron oxidation in sheep, horse and recombinant human apoferritins. PMID- 7887230 TI - Morphologic observations in iron overload: an update. PMID- 7887229 TI - Pathophysiology of iron toxicity. AB - There are several inherited and acquired disorders that can result in chronic iron overload in humans, and the major clinical consequences are hepatic fibrosis, cirrhosis, hepatocellular cancer, cardiac disease, and diabetes. It is clear that lipid peroxidation occurs in experimental iron overload if sufficiently high levels of iron within hepatocytes are achieved. Lipid peroxidation is associated with hepatic mitochondrial and microsomal dysfunction in experimental iron overload, and lipid peroxidation may underlie the increased lysosomal fragility that has been detected in liver samples from both iron-loaded human subjects and experimental animals. Reduced cellular ATP levels, impaired cellular calcium homeostasis, and damage to DNA may all contribute to hepatocellular injury in iron overload. Long-term dietary iron overload in rats can lead to increased collagen gene expression and hepatic fibrosis, perhaps due to activation of hepatic lipocytes. The mechanisms whereby lipocytes are activated in iron overload remain to be elucidated; possible mediators include aldehydic products of iron-induced lipid peroxidation produced in hepatocytes, tissue ferritin, and/or cytokines released by activated Kupffer cells. PMID- 7887231 TI - Identification of thiolic sarcolemmal proteins as a primary target of iron toxicity in cultured heart cells. PMID- 7887232 TI - Iron overload and the biliary route. PMID- 7887233 TI - Changing concepts of haemochromatosis. PMID- 7887234 TI - Epidemiology, clinical spectrum and prognosis of hemochromatosis. AB - EPIDEMIOLOGY: Eleven prospective epidemiological studies from various countries have as yet evaluated the gene prevalence of HLA-linked hemochromatosis. The estimated frequency ranged from 0.027-0.107, the frequency of homozygotes from 0.00074-0.0116, and the frequency of heterozygotes from 0.052-0.191. In a meta analysis of the eleven surveys the frequency is 0.0016 (106/64758 subjects) for homozygotes which corresponds to a gene frequency of 0.041 and a frequency of heterozygotes of 0.078. Further analyses showed that some of these studies have probably underestimated the prevalence which in reality is probably two- to threefold higher than estimated by the meta-analysis. CLINICAL SPECTRUM: In the total group of 251 patients diagnosed with hemochromatosis in the University of Dusseldorf from 1959-1992, abnormality in liver function tests (75%), weakness and lethargy (74%), skin hyperpigmentation (70%), diabetes mellitus (48%), arthralgia (44%), impotence (45% in males), and ECG abnormalities (31%) were the most frequent findings and symptoms at diagnosis. In recent years about 50% of patients were detected without having liver cirrhosis and 20% of patients did not have any symptoms and pathology except iron overload. PROGNOSIS: Survival analysis in the 251 patients showed that in the absence of cirrhosis and diabetes iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. Sex and presence of arthropathy did not predict prognosis. However, patients with massive and long-lasting iron overload had a worse prognosis than patients with less severe iron excess. Iron removal in general ameliorated liver disease, weakness and cardiac abnormalities, and also prevented the progression of endocrine alterations. Therapy, however, did not influence arthropathy which even got worse in several patients. Iron removal also failed to reverse insulin-dependent diabetes. During a mean followup of 13.4 years 69 deaths occurred in the 251 patients. In 19 patients death was due to liver cancer, in 14 due to liver cirrhosis, in 5 due to cardiomyopathy, and in 3 due to diabetes mellitus (all causes significantly more frequent than expected for the general population). The other causes of death were as frequent as expected including extrahepatic malignancies. All liver cancers were seen in cirrhotic livers, but often occurred many years or even decades after complete iron removal. Further strategies have to evaluate the design of screening programs in order to diagnose more patients in the precirrhotic and asymptomatic stage. PMID- 7887236 TI - Genetics of haemochromatosis. PMID- 7887235 TI - The morbidity of hemochromatosis among clinically unselected homozygotes: preliminary report. PMID- 7887237 TI - The transferrin receptor and the release of iron from transferrin. PMID- 7887238 TI - Localization of seven new genes around the HLA-A locus. PMID- 7887239 TI - Searching for the hemochromatosis grail. PMID- 7887240 TI - Iron chelator design. PMID- 7887241 TI - Results from a phase I clinical trial of HBED. AB - In summary, it has been shown that orally administered HBED causes enhanced excretion of iron in all of the thalassemia major patients studied and that both urinary and stool iron are increased in the process. Increasing the dose from 40 to 80 mg/kg divided t.i.d. caused iron balance to increase from 38% to 50%. While this is significantly less than that expected based on our preclinical studies in animals, the potential usefulness of this chelator has been demonstrated. Efforts to increase its oral bioavailability are now in progress. Lending further support to the effort is the fact that no evidence of toxicity has been observed in the studies performed to date and that negative iron balance was achieved in the one thalassemia intermedia patient studied. The results also reinforce the conclusion that DFO causes the excretion of substantially more iron than would be predicted by an assessment of serum ferritin levels or past compliance with chelation therapy. In patients with thalassemia major, serum ferritin levels relate more to tissue damage than to body iron load. Effective chelation therapy can diminish the former much faster than it can remove storage iron. Hence, in cases of iron overload, aggressive chelation therapy should not be tapered off until a significant reduction in iron excretion can be demonstrated. Routine measurements of urinary iron excretion should now be considered essential in the management of beta-thalassemia. Finally, two more patients with thalassemia intermedia will be studied in an effort to substantiate that net negative iron balance can be achieved in this subgroup of patients. We also plan to study several transfused patients in whom the dose of HBED will be increased to 120 mg/kg divided t.i.d. While the chances of achieving net negative iron balance in these patients seems remote, we hope to further demonstrate the safety of this drug with an eye toward the development of an effective prodrug. PMID- 7887242 TI - Lessons from preclinical and clinical studies with 1,2-diethyl-3-hydroxypyridin-4 one, CP94 and related compounds. PMID- 7887243 TI - Iron chelation therapy for malaria. PMID- 7887244 TI - The biochemical basis for the selective antimalarial action of iron chelators on Plasmodium falciparum parasitized cells. PMID- 7887246 TI - Optimized separation and quantitation of serum and cerebrospinal fluid transferrin subfractions defined by differences in iron saturation or glycan composition. PMID- 7887245 TI - The roles of secondary binding sites for transferrin in the liver and on macrophages. PMID- 7887247 TI - Iron absorption and cellular uptake of iron. PMID- 7887248 TI - Ferric iron reduction and iron uptake in eucaryotes: studies with the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. PMID- 7887250 TI - Proceedings of an International Symposium on Taurine in Health and Disease. Cologne, Germany, August 29-September 1, 1993. PMID- 7887249 TI - Cellular responses to iron and iron compounds. PMID- 7887251 TI - Possible relationships between taurine derivatives and products of the metabolism of ketimines. PMID- 7887252 TI - Inhibitors of anion exchanger activity reduce sodium chloride-dependent taurine transport by brush border vesicles. AB - The erythrocyte anion exchanger, or band 3 protein, catalyzes the exchange of chloride and bicarbonate in many cells. Anion exchanger activity is predominantly found in the basolateral membrane of the cortical collecting duct. Because proximal tubular renal taurine uptake across the brush border surface is dependent upon sodium and chloride, the effect of inhibitors of anion exchanger activity on renal taurine accumulation by rat renal brush border membrane vesicles was examined. The anion exchanger probes, DIDS (4,4-'diisothiosulfonic acid), and NBD-taurine (N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl]-aminoethane sulfonic acid), and NBD-taurine (N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] aminoethane sulfonic acid), were used as inhibitors of anion exchanger activity. DIDS, NAP-, and NBD-taurine all markedly inhibit the initial rate of NaCl dependent accumulation of taurine by brush border membrane vesicles. NAP- and NBD taurine accumulation is chloride dependent because inhibition was not found when uptake was performed in the presence of NaNO3 in place of chloride. In the presence of maximal inhibition of taurine uptake by NAP- or NBD-taurine, no additional inhibition was evident after incubation with DIDS. On the other hand, when a competitive inhibitor of taurine uptake, beta-alanine, was used, additional inhibition of taurine accumulation was found in the presence of NAP- or NBD-taurine (p < .01 respectively). These results suggest some interaction of the anion exchanger and the taurine accumulation process at the apical surface of the proximal tubule. Because NBD-taurine is a fluorescent probe, it may be possible to isolate membrane peptides that bind NBD-taurine and demonstrate fluorescence. Preliminary isoelectric focusing experiments of brush border protein incubated with NBD-taurine show fluorescence localized to several particular fractions. Hence this observation that inhibitors of the anion exchanger system block NaCl-dependent taurine uptake can potentially serve as a means of isolating the taurine transporter protein. PMID- 7887253 TI - Expression of taurine transporter and its regulation by diet in Xenopus laevis oocytes following injection of rat kidney cortex mRNA. AB - NaCl-dependent taurine transport adapts to changes in the dietary intake of sulfur amino acids. The renal adaptive response is expressed by enhanced NaCl dependent taurine cotransport by brush border membrane vesicles after a low taurine diet and reduced transport after a high taurine diet as compared to a normal taurine diet. In order to determine if this adaptive regulation is dependent on new protein synthesis, the Xenopus laevis oocyte expression system was utilized to define the translational regulation of taurine transporter activity. Poly(A)+ RNA was isolated from kidney cortex of Sprague Dawley rats fed either a low, normal or high taurine diet for 28 days. Injection of poly(A)+ RNA resulted in a time- and dose-dependent increase in NaCl-taurine co-transport. Taurine uptake was stimulated about 2-10-fold after injection of poly(A)+ RNA (10 40 ng) as compared to H2O-injected oocytes. Taurine uptake by oocytes was sodium- and anion-dependent (Cl- > Br- > SCN- > I-). The Km and Vmax of the taurine transporter were 22.5 microM and 8.35 pmol/h/oocyte respectively, similar to the Km of 17.0 microM found in rat brush border membrane vesicles. Because the adaptive response involves an augmented or reduced Vmax of the transporter, taurine uptake by oocytes injected with poly(A)+ RNA from rats fed each diet was examined. Poly(A)+ RNA from rats fed a low taurine diet elicited twice the taurine uptake elicited from rats fed a normal taurine diet and more than three times the uptake from high taurine-fed rats. Northern blot analysis after hybridization with an RNA probe for the taurine transporter cDNA from MDCK cells (obtained from Dr. Uchida) indicated that the molecular size of taurine transporter mRNA is about 1.9 kb and is regulated by diet. Expression of taurine transporter by the oocytes injected with 30 ng of capped transcript from pNCT was significantly reduced by taurine in the medium. In conclusion, taurine uptake by oocytes after injection of mRNA is similar to brush border membrane vesicles taurine transport. The long-term adaptive response is regulated at the level of mRNA, and the short-term adaptive response is regulated at the level of protein synthesis or secretion. We speculate that the renal adaptive response to altered dietary sulfur amino acid intake is both transcriptionally and translationally regulated. PMID- 7887254 TI - Regulation of taurine transport by external taurine concentration and medium osmolality in renal tubular cells in culture. PMID- 7887255 TI - Role of taurine in the kidney: osmoregulatory taurine accumulation in renal medulla. PMID- 7887256 TI - Taurine and experimental kidney disease. PMID- 7887257 TI - Protecting effect of taurine against hypoxic cell damage in renal tubular cells cultured in different transplant preservation solutions. AB - We conclude that, within this experimental model and under these experimental conditions, taurine supplementation of standard kidney preservation solutions improves survival of kidney cells during hypoxic preservation. The protective effect depends on the taurine concentration, the hypoxic preservation time and the used preservation solution. Physiological taurine concentrations are effective during short hypoxic periods, whereas pharmacological taurine concentrations seem to be needed for longer periods of hypoxia. Within this experimental model University of Wisconsin solution seems to be more effective than Euro collins solution. PMID- 7887258 TI - Mechanisms underlying physiological and pharmacological actions of taurine on myocardial calcium transport. PMID- 7887259 TI - Cardioprotective actions of taurine against intracellular and extracellular calcium-induced effects. AB - The effects of taurine were modulated by the [Ca2+]i or/and [Ca2+]o levels, consistent with recent reports (10, 28, 31). Taurine may directly and indirectly regulate the [Ca2+]i level by modulating Ca2+ channels (dependent on [Ca2+]i/[Ca2+]o) and Na+ channel (via Na(+)-Ca2+ exchange). Thus, taurine antagonizes Ca2+ ([Ca2+]o or [Ca2+]i)-induced cardiac functions. The data for the effects of taurine on the ionic currents and action potentials (automaticity) are summarized in Tables 1 and 2. These results indicate that taurine exerts potent cardioprotective actions under the conditions induced by low Ca2+ level as well as by calcium overload. In conclusion, the effects of taurine are complex, there being a number of actions on cardiac muscle which may show the possible therapeutic use of this sulfur amino acid. PMID- 7887260 TI - Effect of photolytically generated riboflavin radicals and oxygen on hypotaurine antioxidant free radical scavenging activity. PMID- 7887261 TI - Antihypertensive effect of taurine on salt-induced hypertension. PMID- 7887262 TI - The effect of taurine on blood pressure, and urinary sodium, potassium and calcium excretion. PMID- 7887263 TI - New data on the regulation of taurine uptake in cultured nervous cells. PMID- 7887264 TI - Changes in the localization of taurine-like immunoreactivity during development and regeneration in the rat brain. AB - In summary, taurine appeared to be present in certain cell types, such as cerebellar Purkinje cells and hippocampal pyramidal cells, throughout development to adulthood and a differential function for taurine between these periods would be difficult to hypothesize simply based on localization. However, in both the cerebellum and hippocampus, there was a period including post-natal day 7 in the cerebellum and including both post-natal days 7 and 14 in the hippocampus in which taurine appeared not to be confined only to the dendrites of the aforementioned cells, but seemed ubiquitously present in the molecular layers of these two brain regions. This suggests that the taurine may be present in significantly higher concentrations in certain cell types or subcellular structures during development than in the adult rat brain. The elucidation of these taurine-containing structures with the use of electron microscopy may provide some insight into the functions of taurine during these critical periods in development. Finally, taurine appeared to reverse its developmental decline in concentration in the presence of regeneration, suggesting that it may play a role in axonal sprouting and/or synapse formation. PMID- 7887265 TI - Transmitter and electrical stimulations of [3H]taurine release from rat sympathetic ganglia. PMID- 7887266 TI - Cysteine sulfinate decarboxylase in brain: identification, characterization and immunocytochemical location in astrocytes. PMID- 7887267 TI - Relations of taurine release and influx to cell volumes in cerebral cortical slices. PMID- 7887268 TI - Taurine neurons in rat hippocampal formation are relatively inert to cerebral ischemia. PMID- 7887269 TI - Calcium and taurine interaction in mammalian brain metabolism. PMID- 7887270 TI - Regulation of protein kinase C activity by taurine and beta-alanine during excitotoxicity in cat and mouse cerebellar cultures. PMID- 7887271 TI - Volume regulation in cultured neurons: pivotal role of taurine. PMID- 7887272 TI - Taurine as an organic osmolyte in the intact brain: immunocytochemical and biochemical studies. PMID- 7887273 TI - Alterations of ventricular contractility and myofibril loss in taurine-deficient hearts. PMID- 7887274 TI - Developmental effects of taurine depletion on synaptosomal phospholipids in the rat. PMID- 7887275 TI - Taurine depletion and synaptosomal phospholipid content in cat brain. PMID- 7887276 TI - Cell volume regulation in taurine deficient cultured astrocytes. PMID- 7887277 TI - Feline maternal taurine deficiency: effects on visual cortex of the offspring. A morphometric and immunohistochemical study. PMID- 7887278 TI - Effects of postnatal taurine deprivation on visual cortex development in rhesus monkeys through one year of age. PMID- 7887279 TI - The role of taurine in mammalian hearing. PMID- 7887280 TI - The plasma concentration and renal handling of taurine in healthy children and in pediatric patients with disturbed sulfur metabolism. PMID- 7887281 TI - Breast milk taurine and its possible influence on the development of breast milk induced jaundice of the neonate--a hypothesis. PMID- 7887282 TI - Sulphur amino acids and the metabolic response to cytokines. PMID- 7887283 TI - Taurine in the newborn and infant undergoing surgery. PMID- 7887284 TI - Taurine and the lung: pharmacological intervention by aerosol route. PMID- 7887285 TI - Taurine levels in plasma and platelets in insulin-dependent and non-insulin dependent diabetes mellitus: correlation with platelet aggregation. PMID- 7887286 TI - Long-term effect of taurine in congestive heart failure: preliminary report. Heart Failure Research with Taurine Group. PMID- 7887287 TI - Neuroactive amino acids in synaptosomes from focal and nonfocal temporal lobe tissue of patients with intractable complex partial seizures. PMID- 7887288 TI - Expression and regulation of the taurine transporter in cultured cell lines of human origin. PMID- 7887289 TI - Dietary taurine requirement of cats is determined by microbial degradation of taurine in the gut. PMID- 7887290 TI - Reactivity of taurine with aldehydes and its physiological role. AB - The chemical reactions of the amino group of taurine with aldehydes were investigated. Glucose, acetaldehyde, and malondialdehyde were used as aldehydes. After taurine had reacted, the amounts of remaining taurine and aldehydes were measured, and the reactivity was evaluated. Amino acids such as glycine, alpha alanine, and beta-alanine were compared because of their structural resemblance to each other. Taurine showed a high reactivity with each one of the aldehydes tested. It is known that protein is altered through reactions of the amino group with various aldehydes. Low density lipoprotein (LDL) was used as a model protein and the inhibiting effect of taurine against the modification of LDL by malondialdehyde was examined. It was shown that the inhibiting effects of taurine correlated with the reactivity of malondialdehyde with amino acids. Further, the taurine-glucose reaction product showed an antioxidative effect on the peroxidation of liposomes made of yolk phosphatidylcholine as a biomembrane model. The results suggest the possibility of an inhibiting effect of taurine against the modification of protein, as well as an antioxidative effect through the reactions of taurine with aldehydes in vivo. PMID- 7887291 TI - Hepatic regulation of cysteine utilization for taurine synthesis. PMID- 7887292 TI - The inhibitory effects of taurine on protein phosphorylation: comparison of various characteristics of the taurine-affected phosphoproteins present in rat retina, brain and heart. PMID- 7887294 TI - Effects of taurine on microsomal enzyme activities involved in liver lipid metabolism of Wistar rats. PMID- 7887293 TI - Immunohistochemical localization of taurine-conjugated bile acids in the liver of mouse, rat, monkey and human. PMID- 7887295 TI - Signaling and internalisation function of the B cell antigen receptor complex. PMID- 7887297 TI - Nonreceptor tyrosine kinases in aggregation-mediated cell activation. PMID- 7887296 TI - The role of Syk in cell signaling. PMID- 7887298 TI - Control of lymphopoiesis by non-receptor protein tyrosine kinases. PMID- 7887299 TI - Involvement of nonreceptor protein tyrosine kinases in multichain immune recognition receptor signal transduction. PMID- 7887300 TI - Phorbol myristate acetate-induced changes in protein kinase C isozymes (alpha, beta, gamma and zeta) in human T cell subsets. PMID- 7887302 TI - Quantitative aspects of receptor aggregation. PMID- 7887301 TI - Cloning and characterization of NF-ATc and NF-ATp: the cytoplasmic components of NF-AT. AB - Present evidence indicates a pathway of signal transmission in T cells that is outlined in figure 1. The elevation in intracellular calcium that is induced by interactions at the antigen receptor leads to the activation of the calcium dependent phosphatase calcineurin. This in turn leads to the nuclear association of the cytosolic component of NF-ATc. The activation of calcineurin and the nuclear import of NF-ATc can both be blocked by cyclosporin A or FK506 in complex with their respective immunophilins. Once in the nucleus, NF-ATc interacts with NF-ATn to form an active transcriptional complex. NF-ATn is a ubiquitous protein, can be synthesized in response to PMA, and has many similarities to AP-1. The mechanism by which NF-ATc enters the nucleus is unknown, and although it appears to require calcineurin, NF-ATc has not yet been shown to be an in vivo substrate of calcineurin. Alternative mechanisms include the possibility that NF-ATc operates on some cytoplasmic anchor or that other proteins that are controlled by calcineurin carry out the nuclear import of NF-ATc. Although NF-ATp copurifies with NF-ATc, there is as yet no understanding of how NF-ATp is functioning in vivo. Now that these proteins are purified and cloned, the major goals will be to understand their role and the roles of other family members in thymic development. PMID- 7887303 TI - Fc receptor signaling. PMID- 7887304 TI - Proximal signals and the control of S-phase entry in interleukin-2-stimulated T lymphocytes. PMID- 7887305 TI - The IL-4 receptor--signaling mechanisms. PMID- 7887306 TI - Function of the common beta subunit of the GM-CSF/IL-3/IL-5 receptors. PMID- 7887307 TI - Sharing of a common gamma chain, gamma c, by the IL-2, IL-4, and IL-7 receptors: implications for X-linked severe combined immunodeficiency (XSCID). PMID- 7887308 TI - B-cell activation by wild type and mutant Ig-beta cytoplasmic domains. AB - In B lymphocytes, the cytoplasmic domains of the membrane immunoglobulin associated heterodimeric Ig-alpha and Ig-beta proteins link membrane immunoglobulin to intracellular signalling molecules. We constructed chimeric genes encoding the extracellular and transmembrane domain of human CD8 alpha and the cytoplasmic domain of Ig-alpha or Ig-beta and examined the ability of the chimeric proteins to induce signalling in the murine B-cell lymphoma A20. Crosslinking of CD8/Ig-alpha or CD8/Ig-beta induced both calcium mobilization and protein tyrosine phosphorylation, although induction by CD8/Ig-alpha was somewhat stronger. We also carried out mutagenesis of residues within the "Reth" motif of the CD8/Ig-beta cytoplasmic domain and determined the effects of these mutations on signalling in the murine B-cell hybridoma LK 35.2. Mutants in which alanine was substituted for glutamine 202, threonine 205, and isoleucine 209 retained the ability to induce protein tyrosine phosphorylation and calcium mobilization. In contrast, substitution of alanine for leucine 198 abrogated these responses, suggesting a critical role for this residue in interaction with cytoplasmic signalling proteins. PMID- 7887309 TI - X-linked agammaglobulinemia and Bruton's tyrosine kinase. PMID- 7887310 TI - Involvement of the protein tyrosine phosphatase PTP1C in cellular physiology, autoimmunity and oncogenesis. PMID- 7887311 TI - Accessory molecules that influence signaling through B lymphocyte antigen receptors. PMID- 7887312 TI - Analysis of the (YXXL/I)2 signalling motifs found in the cytoplasmic segment of the mouse CD3-zeta chain. PMID- 7887313 TI - Molecular and genetic insights into T cell antigen receptor signal transduction. PMID- 7887314 TI - Signal transduction during T cell development. PMID- 7887315 TI - The regulation and function of p21ras in signal transduction by the T cell antigen receptor. PMID- 7887316 TI - Immunological tolerance by antigen-induced apoptosis of mature T lymphocytes. PMID- 7887317 TI - Mechanism of B cell antigen receptor function: transmembrane signaling and triggering of apoptosis. AB - The antigen receptor of B lymphocytes (BCR) plays important roles in virtually every stage in the development, inactivation, or activation of B cells. The BCR is a complex of membrane immunoglobulin (mIg) and a heterodimer of two transmembrane polypeptides called Ig-alpha and Ig-beta. Site directed mutation of the mu immunoglobulin heavy chain has demonstrated that the mu transmembrane domain plays a key role in the assembly of mIgM with Ig-alpha/Ig-beta. In addition, there is a strong correlation between the ability of various mutant mIgM molecules to associate with Ig-alpha/Ig-beta and their ability to induce signal transduction reactions such as protein tyrosine phosphorylation and phosphoinositide breakdown. The cytoplasmic domains of Ig-alpha and Ig-beta share a region of limited homology with each other and with components of the T cell antigen receptor and of the Fc receptor. The presence of regions of the cytoplasmic domains of Ig-alpha or Ig-beta including this conserved amino acid sequence motif is sufficient to confer signaling function on chimeric transmembrane proteins. Both Ig-alpha and Ig-beta chimeras are capable of inducing all of the BCR signaling events tested. Based on these and related observations, we propose that the motifs act to initiate the BCR signaling reactions by binding and activating tyrosine kinases. Among the important events mediated by BCR signaling is induced expression of a series of genes referred to as early response genes. In B cells these include transcription factors and at least one component that regulates signaling events. One of these genes, c-myc, appears to play an important role in mediating apoptosis in B cells stimulated via the BCR complex. PMID- 7887318 TI - Properties of Ca currents activated by T cell receptor signaling. PMID- 7887320 TI - [Changes in proliferation and differentiation of basal cells during wound healing of rabbit corneal epithelial abrasions]. AB - Changes in the mitotic rate and epithelial keratin expression of corneal epithelial basal cells following corneal abrasion (7.0 mm in diameter) in rabbits were studied immunohistochemically using antiproliferating cell nuclear antigen (PCNA) monoclonal antibody and anti-epithelial keratin 1 (AE1). In the non wounded control, the mitotic rate (PCNA positive cells in the basal cell layer) was approximately 4%, and only the superficial cells were stained by AE1 monoclonal antibody. One day after wounding, migrating epithelial cells at the leading edge, which reacted to AE1, showed low mitotic activity. At days 3 and 7, the mitotic rates of basal cells of regenerating epithelium were 3 times higher than that of controls. These basal cells displayed intensive staining with AE1, while the epithelium over the unwounded cornea exhibited a normal pattern limited to superficial cells. By 14 days after injury, the mitotic rate returned to normal and all epithelial cells expressed a normal AE1 staining pattern. Theses results suggest that regeneration of corneal epithelial basal cells involves changes in keratin expression, which might correlate with changes in the mitotic rate. PMID- 7887319 TI - [Wound healing in the cornea]. PMID- 7887321 TI - [A case of Sneddon syndrome]. AB - Sneddon syndrome is a clinical entity that is characterized by livedo reticularis and cerebrovascular lesions and is considered to be a subtype of antiphospholipid antibody syndrome. Central retinal artery occlusion is one of the ophthalmic complications of this syndrome and its prognosis of visual acuity is generally poor. We report here a 50-year-old man with Sneddon syndrome who had recurrent central retinal artery occlusion with recovery of visual function after each episode. PMID- 7887322 TI - [A case of suprasellar arachnoid cyst followed up for a long time]. AB - We followed a case of suprasellar arachnoid cyst for 12 years. The patient was a sixteen-year-old girl without particular problems in her general condition. She showed optic atrophy in both eyes and optic nerve hypoplasia with an inferotemporal quandranopsia in the left eye. A suprasellar arachnoid cyst communicating with the tubarachnoid space was found to extend into the sella turcica as an empty sella. A cyst wall was resected and a cyst-peritoneal shunt performed. After 12 years from the operation, sensitivity was slightly depressed in the visual field where it had already been disturbed. Although there are few reports in the literature on involvement of the optic nerves and chiasma by suprasellar arachnoid cysts, papilledema and optic atrophy are often found in children, and infero-temporal quandranopsia or homonymous hemianopsia have been reported. Visual field defects were most likely caused by compression of the optic nerve by cyst or prolonged papilledema. We also suspect that some kind of disturbance to the optic nerve occurred during extension of the arachnoid cyst as an empty sella, or during formation of arachnoid cyst in the fetus stage. PMID- 7887323 TI - [The effect of epidermal growth factor on corneal endothelial wound healing in rabbits]. AB - We investigated the effect of epidermal growth factor (EGF) on rabbit corneal endothelial wound healing in vivo. After a 6 mm-diameter metallic cryoprobe was applied to rabbit corneas, 0.1 ml of recombinant human EGF (100 micrograms/ml) or saline was injected into the anterior chamber. Corneas were excised on 1, 2, and 7 days postoperatively, labeled with 3H-thymidine and subjected to autoradiography. Some corneas were examined by scanning electron microscopy. Autoradiography showed that the number of endothelial cells incorporating 3H thymidine in corneas treated with EGF was significantly greater than that in the control. Scanning electron microscopy demonstrated the effect of EGF on accelerating endothelial healing. These findings indicate that EGF has a stimulatory effect on the proliferation of wounded rabbit corneal endothelial cells in vivo. Under the conditions tested in the present study, there were no side effects of EGF such as neovascularization or cellular proliferation in the angle. The results suggest that EGF might be clinically applicable for corneal endothelial disorders. PMID- 7887324 TI - [Changes of expression in matrix metalloproteinase and its inhibitor level in the sclera from axially elongated eyes]. AB - We studied the gelatinolytic activity, caseinolytic activity and the level of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the sclera from experimentally induced axially elongated eyes. The animal models were made by the injection of 250U alpha-chymotrypsin into the posterior chamber of young albino rabbits. Animals were killed with overdoses of intravenous pentobarbital and eyes were enucleated gently. Sclera from the equatorial area was then subjected to organ culture. The enzyme activity in the media was investigated by zymography using gelatin- or casein-containing gels together with an image analyzer system. TIMP-1 levels in each medium were measured by enzyme immunoassay (EIA). All samples showed three major bands of gelatinolytic activity at molecular weights of 87, 61, and 57 kDa. Gelatinolytic activity of 87 kDa increased 1.1 to 2.9 times compared with control sclera. All of the caseinolytic activity (87, 82, 52, and 50 kDa) was also elevated 1.8 to 6.6 times in samples from experimental eyes. TIMP-1 levels were mildly increased (up to 1.41 times) in the experimental eyes. These data suggest that degradation processes might be accelerated in the sclera from experimentally induced elongated eyes. PMID- 7887325 TI - [Collagen synthetic activity following filtration surgery in rabbits]. AB - We evaluated collagen synthetic activity, which plays an important role in wound healing, following experimental filtration surgery in rabbits. Collagen synthetic activity was measured by immunohistochemistry for prolyl 4-hydroxylase beta subunit and type I procollagen. Trabeculectomy was performed on albino rabbit eyes, with the filtering site harvested on postoperative days 1, 4, 7, 14, and 28. Samples were fixed with 10% buffered formalin for 12 hours and prepared for paraffin section, and each antigen was detected in filtering site tissue using avidin-biotinylated peroxidase complex. Immunoreaction of prolyl 4-hydroxylase beta-subunit or type I procollagen increased from day 4 to 14 and markedly decreased at day 28. These findings show that prolyl 4-hydroxylase and type I procollagen are markedly produced almost simultaneously, and collagen synthetic activity following filtration surgery continues for over 14 days in the process of wound healing. PMID- 7887326 TI - [The role of the basal cell layer in the maintenance of normal corneal epithelium]. AB - A method of desquamating single layers of corneal epithelial cells through the use of digitonin allowed the observation of the basal cell layer by scanning electron microscope. Basal cells of normal rabbit corneal epithelium were observed as small, round, and columnar-shaped cells, and the mean cell areas of superficial and basal cell layers were 507. 3 +/- 46.6 microns 2, and 39.5 +/- 2.8 microns 2, respectively. The mitotic rate of basal cells was also evaluated immunohistochemically using anti-PCNA (proliferating cell nuclear antigen) monoclonal antibody and the flat preparations of corneal epithelium. The mitotic rate (PCNA positive cells in the basal cell layer) was approximately 4%, and showed no difference between the center and peripheral portion of the cornea. We think these two new methods are useful for the analysis of morphological and functional characteristics of corneal epithelial basal cells. PMID- 7887327 TI - [Effects of vanadate on glucose metabolism in the lens of rats with streptozotocin-induced diabetes--ketohexokinase and aldolase activity]. AB - The effects of vanadate, an oxidized form of vanadium, on glucose metabolism of the lens in diabetic rats were studied. Five-week-old male Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin (50 mg/kg). One week later, the diabetic rats were given 0.2 g/l NaVO3 -5g/l NaCl solution in drinking water ad libitum for 2 weeks and biochemical parameters in their lenses were determined. Blood glucose levels significantly decreased in the vanadate-administered diabetic rats (DV group), compared with the diabetic rats given no vanadate (D group). In the DV group, a significant decrease was observed in lens fructose content compared with the D group. Lens ketohexokinase activity tended to be higher and lens aldolase activity was significantly higher in the DV group than in the D group. These results indicate that vanadate accelerates the metabolic reaction from sorbitol pathway to glycolysis. PMID- 7887328 TI - [Effect of systemic calcium antagonist on a model of ocular circulation disturbance induced by endothelin-1]. AB - We studied the effect of generally applied calcium antagonist on endothelin (ET 1) treated rabbit eyes. Nicardipine (20 micrograms/kg) was injected intravenously 15 minutes before intravitreal injection of 10 microliters of ET-1 at 10(-6) M. We measured the relative caliber of the retinal artery (the caliber of the retinal artery at the edge of the optic nerve head (ONH)/that of ONH), the capillary blood flow in ONH, visual evoked potential (VEP), intraocular pressure (IOP), and blood pressure (BP). In the control group (0.4 ml/kg of saline), administration of ET-1 caused contraction of the retinal artery, decrease of the capillary blood flow in ONH, prolongation of the VEP latency, and reduction of IOP. But these effects were significantly reduced in the calcium antagonist group. These results showed that generally applied calcium antagonist inhibits the disturbance of ocular circulation induced by ET-1. However, it also caused significant reduction of BP until 45 minutes after application, so we will have to work to find the optimum dose of calcium antagonist. PMID- 7887329 TI - [Neurons in monkey parietal association cortex sensitive to axis orientation]. AB - Patients with parietal lesions may fail to adjust the orientation of the hand to that of the target object or may make errors in judging the orientation of the bar. This suggests that the parietal cortex functions to discriminate the orientation of objects. Therefore, we studied orientation selectivity of the visual neurons of the posterior parietal association cortex of alert behaving monkeys. We recorded 23 neurons that showed selectivity in the axis orientation of visual stimulus in the lateral bank and fundus of the caudal part of the intraparietal sulcus (IPS). Almost all the neurons tested with a slit on the screen responded better to a longer or narrower stimulus. There were also neurons which responded only to three dimensional objects, such as a bar presented in the sagittal orientation tilted forward or backward. The majority of these neurons had wide receptive fields and their responses were position-invariant. These results suggest that the axis orientation selective neurons of the parietal cortex represent orientation of the longitudinal axis of objects in 3-dimensional space. PMID- 7887330 TI - [A nation-wide survey on the occurrence of amoebic keratitis in Japan]. AB - Acanthamoeba keratitis in Japan was first reported by Ishibashi in 1988. Since then, the incidence of Acanthamoeba keratitis has gradually increased. We retrospectively analyzed 39 cases, 42 eyes, of amoebic keratitis reported in Japan from 1988 to September 1993. Of the 39 patients, 35 (89.7%) wore contact lenses, 32 (82.1%) soft contact lenses, and 3 (7.7%) hard contact lenses, and 4 (10.3%) did not wear contact lenses. Of the 4 patients without contact lenses, 3 had a history of trauma. Acanthamoeba keratitis is often difficult to diagnose. Twenty-four cases were misdiagnosed as herpetic keratitis. Early diagnosis and adequate therapy are important. PMID- 7887331 TI - [Experimental studies on influence of alignment errors on measurement in a corneal topographic system--relationship between degree of measurement error and working distance]. AB - To evaluate the influence of alignment errors in focusing on the results of measurements in corneal topography, we experimented using polymethyl-methacrylate balls with definite radii of curvature as test objects. We used 3 different corneal topographic systems with different working distances to clarify the relationship between the degree of errors and the working distance. We determined the refractive power of the test balls by the topographic systems and studied changes in the values as the balls were slightly displaced from the alignment position axially, or horizontally. The test balls were set on the stage with a micrometer so that the distance of displacement could be determined precisely. When the test balls were placed precisely in alignment, there was no significant relationship in the magnitude of measurement errors with working distance of the topographical systems. When the test balls were displaced axially, the measurement values decreased as the balls come near from the alignment position and increased as they moved away from the alignment position. The magnitude of the measurement errors caused by back and forth displacement of the object became larger as the working distance of the topographic system became shorter. There was no specific relationship between the degree of measurement errors and the working distance when the balls were displaced horizontally. PMID- 7887332 TI - [The existence of epidermal growth factor and basic fibroblast growth factor in human lens epithelial cells]. AB - The aqueous humor supplies the lens with nutrition. Recently, the existence of epidermal growth factor (EGF) and basic fibroblast growth factor (b-FGF) has been confirmed in the human aqueous humor. For this reason, it was thought that the function of these growth factors was related to the physiological condition of the lens epithelial cells (LEC). Therefore, we looked for the existence of receptors for EGF, FGF, and the internalization of EGF and b-FGF using LEC from human cataractous lenses in immunohistochemistry. We confirmed the existence of receptors for EGF and FGF as well as the internalization of EGF and b-FGF. From these results. We inferred that the function of EGF and b-FGF was strongly related to the physiological condition of LEC. PMID- 7887333 TI - [Comparative study on frequency-doubled Nd: YAG laser, krypton laser and diode laser photocoagulation for diabetic maculopathy]. AB - Twenty six eyes of thirteen patients with diabetic maculopathy (Fukuda's classification AI, AII, BI) were treated with frequency-doubled Nd:YAG laser (6 eyes) or krypton laser (7 eyes) in one eye and diode laser (13 eyes) in the other eye. Group A was treated with frequency-doubled Nd: YAG laser and diode laser, and group B was treated with krypton laser and diode laser. The visual acuity, visual field (Octopus program 31) and fundus were examined at one month, 3 months, and 6 months after photocoagulation. Visual acuity was stable in all eyes. The central 30 degree visual sensitivity decreased more after diode laser treatment than after that of the other lasers. Krypton laser photocoagulation maintained the better visual function and was easy to use followed by frequency doubled Nd: YAG laser. Because the appearance immediately after diode laser lesion was weaker than one hour after coagulation, it was difficult to get the proper power setting. PMID- 7887334 TI - [Incidence of acute idiopathic optic neuritis and its therapy in Japan. Optic Neuritis Treatment Trial Multicenter Cooperative Research Group (ONMRG)]. AB - Data on the incidence of and treatment for acute idiopathic optic neuritis were obtained by questionnaire sent to departments of ophthalmology, university hospitals, and general hospitals throughout Japan. Inquiry was made as to the number of cases which developed idiopathic optic neuritis from April 1992 to March 1993 along with their clinical features. The response rate was 53.6%. There were a total of 550 cases, and the male to female ratio was 1:1.22. Patients 14 to 55 years old were 65.9%; bilateral involvement: 28.2%; recurrence: 18.6%; positive past history of the other eye; 7.5%. Assuming the answering rate to be 100% and two thirds of the patients to be included, annual incidence of this disease (the annual number of patients) was determined to be 1.62 for an adult population of 100,000 (1.03 cases/100,000 people). Tochigi, Tokyo, Kanagawa, Hyogo, Wakayama, Okayama, Yamaguchi, Tottori, Shimane, Ehime, and Fukuoka showed an annual incidence exceeding 2.0/100,000 adults. At more than 95% of all medical institutions questioned, patients with optic neuritis were usually treated with systemic corticosteroids. Oral corticosteroid therapy, which was shown in a recent study in USA to be contraindicated, was still being used at 15% of the institutions. PMID- 7887335 TI - [A case of cutaneous malignant melanoma metastatic to the choroid]. AB - A case of metastasis of cutaneous malignant melanoma to the choroid was reported. The patient, a 61-year-old man, had undergone an amputation of his right first finger 3 years ago due to cutaneous malignant melanoma. Ophthalmoscopic examination revealed a whitish yellow elevated choroidal lesion and serous retinal detachment in the left eye. Fluorescein angiography demonstrated multiple pinpoint leaks in the early phase and progressive pooling of dye into the subretinal space in the late phase. In magnetic resonance imaging, the tumor showed a hyperintense image in both T1 and T2-weighted images. Autopsy was performed and histopathological examination of the eye showed that the tumor cells were polygonal in shape, and had round or oval nuclei, but the cytoplasms had little melanin pigment. Immunohistochemistry for S-100 and HMB-45 antibody showed positive staining in choroidal tumor and other metastatic lesions, indicating that they were metastatic tumors from cutaneous malignant melanoma (amelanotic melanoma cells). PMID- 7887336 TI - Antibody isotypes profiles against Trypanosoma cruzi acidic antigens in two Amerindian populations from a Chagas' disease endemic area. AB - The isotype distribution of the antibody response against one Trypanosoma cruzi antigenic fraction, FIV, and the putative association to heart disease were analyzed in patients of two apparently genetically distinct Amerindian populations, Mataco (M) and Toba (T), infected with this parasite. The isotypes profiles were analyzed by ELISA, and the antigen specificity of IgG immune response was determined by the immunoblot method. The percentages of infected individuals with abnormal electrocardiograms (GII) were 50% for population M and 10% for population T. Many individuals from both populations had measureable IgG2, IgG3 and IgG4 antibodies to FIV, but the level and frequency (%) of positive sera in population T was considerably higher than in population M (70% vs 15% for IgG2; 75% vs 40% for IgG3; 85% vs 20% for IgG4). The level and frequency of IgG1 reactivity against FIV were similar in the two populations. When the sera were titrated, the most remarkable difference in isotype levels between populations T and M was seen for IgG2 and IgG4, the T population showing the highest titer. No association between clinical state and a particular isotype profile was found by ELISA in any population. When the antigen specificity of antibody response was determined by immunoblot, the antigen patterns recognized by sera from the two clinical groups showed some differences only in population M. All sera assayed from GII of population M fixed more IgG than those with normal electrocardiograms (GI). Two bands of 36 and 43 kD were revealed only in GII of this population. Similar antigenic patterns between the two clinical groups from population T were observed, and they were comparable with those obtained with GI from population M. PMID- 7887337 TI - Schistosoma haematobium infection patterns in the Rahad Irrigation Scheme, Sudan. AB - Patterns of infection of urinary schistosomiasis (Schistosoma haematobium) were studied in 4 highly endemic village areas in the Rahad Irrigation Scheme, Sudan. The prevalence of S. haematobium infection in the total study population of 4725 individuals was 30%, and the age-prevalence and age-intensity figures increased rapidly to reach their maxima in the younger age groups. The overall prevalence of infection among males (31.7%) was slightly higher than among females (28.7%), and the two sexes differed in their age-specific prevalence patterns. The pattern of intensity of infection in males and females was rather similar. Marked differences in prevalence and intensity of S. haematobium infection were recorded between the four village areas, and the infection level in camp inhabitants exceeded markedly that in village inhabitants. Specific problems related to low school attendance rates, limited use of treatment opportunities provided at health centers and less than optimal efficacy of the focal snail control approach taken may be kept responsible for the fact that the control programme implemented in the Scheme has not achieved transmission control. PMID- 7887338 TI - Control of Schistosoma mansoni and intestinal helminths: 8-year follow-up of an urban school programme in Bujumbura, Burundi. AB - Annual selective chemotherapy with praziquantel was implemented in primary schools in the endemic suburbs of Bujumbura from 1984 to 1992. During the first 6 year period, the overall prevalence among pupils decreased from 23.3% to 9.1%, a reduction of 61%. During the following 2-year period, in which only children from the 1st, 4th and 6th grade were examined in two of the four endemic suburbs (maintenance strategy), the prevalence decreased further to 6.4% or a 73% reduction from the beginning of the programme. The impact of annually repeated selective chemotherapy was more important on the intensity than on the prevalence of infection. It was also more pronounced in the senior grades of primary school. Its cumulative effect tended to decline over the years. The prevalence of infection in new entrants to the programme also decreased over the years, indicating a reduction of transmission. This change in transmission was different in each suburb and related to changes in the sanitary situation, the degree of urbanization and the accessibility to rural transmission sites. The results of helminth control, a secondary aspect of the school programme, were proportionately less pronounced than those obtained for schistosomiasis. The improvement in hygienic conditions has also contributed much to the outcome of this latter type of control. The cost, per person protected, of the programme was comparable with what has been reported by other, similar programmes. Application of a maintenance strategy to 57% of the target population has reduced the cost by 40%. PMID- 7887339 TI - Uptake and efflux of chloroquine by chloroquine-resistant Plasmodium falciparum clones recently isolated in Africa. AB - In recently isolated African Plasmodium falciparum clones, the intracellular chloroquine concentration at steady-state, under standard culture conditions, could not differentiate chloroquine-sensitive from resistant parasites. However, under an atmosphere of air the chloroquine-resistant P. falciparum clones released pre-accumulated [3H]chloroquine more rapidly than sensitive clones. The very fast efflux of the pre-accumulated drug from chloroquine-resistant (CQR) parasites resulted in a differential in the drug retained by resistant and sensitive parasites. The chloroquine-sensitive parasites retained 2-3 times more chloroquine than resistant parasites. The steady-state uptake of [3H]chloroquine appeared to be enhanced by verapamil and desipramine in the chloroquine-resistant clones, while the opposite was observed with sensitive clones. This confirmed the suggestion that verapamil inhibits the rapid efflux in CQR parasites resulting in a readily detectable increase in chloroquine accumulation. These observations indicate that the biochemical phenotypes of African chloroquine-resistant P. falciparum are similar to those reported from S.E. Asia and Latin America and are consistent with a common molecular basis for the phenomenon. PMID- 7887340 TI - Time to death from starvation and compulsive killing by the larvae of Toxorhynchites splendens (Diptera: Culicidae). AB - Time to death from starvation and compulsive killing without eating of the prey by larvae of Toxorhynchites splendens were studied in the laboratory. The first and second instars survived without food for 3 days while third and fourth instars survived for 7.8 and 14 days, respectively. When the corresponding instars of Aedes aegypti, Anopheles stephensi or Culex quinquefasciatus were offered, the number of prey killed but not eaten ranged from 0 to 15 per 40 prey larvae. Compulsive killing of Ae. aegypti was mainly at its third instar by 9- and 10-day old T. splendens. Compulsive killing of An. stephensi was mainly at its second and third instars by young and older ages of T. splendens but older T. splendens also killed fourth instar of An. stephensi. Compulsive killing of Cx. quinquefasciatus was of all its instars and mainly by young T. splendens. There was a significant negative correlation between the amount of food eaten per predator and the number of prey killed compulsively. The number of larvae killed and eaten were much larger than number killed compulsively, except in the case of third instar Ae. aegypti and 9-10-day old T. splendens. PMID- 7887342 TI - Monitoring of clinical, parasitological and serological parameters during an experimental infection of capybaras (Hydrochaeris hydrochaeris) with Trypanosoma evansi. PMID- 7887341 TI - Investigations on naturally occurring Trypanosoma evansi infections in horses, cattle, dogs and capybaras (Hydrochaeris hydrochaeris) in Pantanal de Pocone (Mato Grosso, Brazil). AB - The prevalence of Mal de Cadeiras--Portuguese for Trypanosoma (T.) evansi infections in horses--as well as the prevalence of T.evansi infections in cattle, dogs and free-ranging capybaras (Hydrochaeris hydrochaeris) was investigated in Pantanal de Pocone (Mato Grosso, Brazil). In 0.3, 8.6 and 8.0% of the horses, dogs and capybaras, respectively, infection was detected using standard parasitological methods. A seroprevalence of 4.1, 2.3, 7.1 and 22.0% was found in horses, cattle, dogs and capybaras, respectively, using an enzyme-linked immunosorbent assay for the detection of T.evansi antigen (Ag-ELISA), whereas 9.6, 4.2, 18.6 and 14.0% of the animals investigated were reactive in a T.evansi antibody (Ab-) ELISA. Positive ELISA results ('high responders') were identified using computer-assisted mixture analysis (C.A.MAN). Agglutinating antibodies were detected by the T.evansi card agglutination test for trypanosomiasis (CATT/T.evansi) in 14.6%, 1.3%, 15.7% and 22.0% of the horses, cattle, dogs and capybaras, respectively. A moderate but significant (kappa test; p < 0.05) agreement beyond chance level was observed between Ab-ELISA and CATT results but generally not between antibody and antigen detection tests. Therefore, in an attempt to maximize the information yield of the three serodiagnostic tests, their results were numerically scored (negative = 0, intermediate = 1, positive = 2) and added up to a total score (TS) which was considered indicative for infection when TS > or = 4 (results of the Ag-ELISA received double weight). Estimates of seroprevalence according to TS were 13.2, 4.7, 30.0 and 24.0% for horses, cattle, dogs and capybaras, respectively. Identical isoenzyme profiles, known as zymodeme 58 (T.evansi MCAN/BR/86/H), were found in all T.evansi stocks isolated in the study area (six from dogs, one from a horse and one from a capybara). From the results of this study it can be inferred that Mal de Cadeiras is endemic in Pantanal de Pocone. Although clinical and parasitological findings support the possible role of the capybara as a reservoir host of T.evansi, dogs and cattle--due to their close contact with horses--should rather be regarded as efficient reservoir hosts for Mal de Cadeiras in the study area. PMID- 7887343 TI - A simple method to separate metacyclic forms of Trypanosoma cruzi from axenic cultures. PMID- 7887344 TI - Comparison of age-dependent antigen recognition in two communities with high and low Trichuris trichiura transmission. AB - A previous ELISA-based study using whole worm extract, compared age-antibody profiles in two communities with high and low levels of Trichuris trichiura transmission (Needham et al., 1992). This showed that specific IgG1 levels mirrored infection intensity at the population level, while IgA levels exhibited a weak trend to remain elevated in the adult age classes in the area of highest transmission. This was interpreted as preliminary evidence for IgA-mediated resistance in the population with greatest prior experience of infection. The present study extends this work to compare IgG1 and IgA isotype recognition of separated antigens by Western blot between the two communities. Comparison of age dependent antigen recognition in the two communities shows that both qualitative and quantitative recognition by IgG1 antibodies is related to the current intensity of infection (as assessed by eggs per gram of faeces, epg). The magnitude of the IgA response to separated antigens of 16-17 kDa and 90 kDa exhibits a stronger trend to remain elevated in adults and to reflect the past experience of infection: IgA antibodies are present at significantly higher levels in adults from the high transmission area compared with those from the community with low levels of T. trichiura endemicity, despite infection levels in these age groups being of similar magnitude. This comparative study therefore, provides further evidence to support a role for IgA in acquired immunity to T. trichiura in areas of intense transmission. PMID- 7887346 TI - Opportunities to preserve vision in diabetic patients. PMID- 7887345 TI - Prolonged suppression of trichostrongyle egg output of N'Dama cattle by a single larvicidal treatment. AB - Gambian village cattle herds were treated with a single dose of ivermectine (Ivomec, MSD-AGVET Inc. 1 ml/50 kg body weight) during the dry season. This treatment suppressed the trichostrongyle egg rise prior to the rains and led to delayed egg production for at least 6 months after the onset of the rainy season, compared to untreated animals from neighbouring villages. However, the results clearly indicate that a single treatment with ivermectine during the dry season does not lead to complete suppression of the gastrointestinal strongyle infections, since a worm population still gradually built up. During the second year the ranked level of the egg excretion was significantly lower than that of the control group throughout the year until December, except in August. The results further support the hypothesis that trichostrongyle reinfection is unimportant during the dry season in this climatic zone. PMID- 7887347 TI - Building bridges, not walls: caring for the adolescent. PMID- 7887348 TI - Head concussion guidelines. PMID- 7887349 TI - Trapezial avascular necrosis. PMID- 7887350 TI - Shortcut for quantifying proteinuria on urinalysis. PMID- 7887351 TI - Pelvic pain from cholelithiasis in a patient with kyphoscoliosis. PMID- 7887352 TI - 'No' to another bureaucracy. PMID- 7887353 TI - A mnemonic for asthma care. PMID- 7887354 TI - Overcoming medical and social barriers to breast feeding. PMID- 7887355 TI - Management of diabetic retinopathy. AB - All persons with diabetes are at risk of retinal complications, although persons with type I (insulin-dependent) diabetes face a greater danger of severe vision loss than persons with type II (noninsulin-dependent) diabetes. Retinopathy has two stages: the nonproliferative stage, which includes intraretinal microaneurysms, hemorrhages, and soft and hard exudates, typically occurs well before the more serious proliferative stage, which is characterized by neovascularization and fibrovascular growth from the retina or optic nerve. Macular edema, a serious development, can occur in either stage. Untreated neovascularization and macular edema are the two major retinal complications that lead to blindness. Good glycemic control has been shown to reduce the development of retinopathy by 76 percent in diabetic patients and to slow progression by 54 percent in those with early retinopathy. Effective hypertension control and diabetic therapy, regular ophthalmologic examinations and properly timed focal laser treatments for macular edema and proliferative retinopathy can markedly reduce the risk of vision loss. PMID- 7887356 TI - Acute knee injuries: Part II. Diagnosis and management. AB - The most common acute knee injuries are collateral ligament sprains, meniscal damage, cruciate ligament sprains and patellar dislocation or subluxation events. Initial treatment for these soft tissue injuries includes rest, ice application, compression and elevation for the first 24 to 72 hours, as well as anti inflammatory medication. Accurate assessment, utilizing a thorough history and physical examination and judicious use of radiographic studies, facilitates proper management and return to activity. Athletic patients should be offered the option of surgical reconstruction. PMID- 7887357 TI - Urticaria. AB - Urticaria (hives) is a common disorder that affects 15 to 20 percent of the population at some time. Lesions are clinically characterized by a transient, pruritic, patchy eruption that consists of lightly erythematous papules or wheals. When attacks are protracted, urticaria is an annoying condition for the patient and a challenge for the physician. Foods, drugs and many other agents may cause urticaria by inducing mediator release from mast cells in the skin. Identification of the precipitating agent is crucial for effective treatment of urticaria. Newer antihistamines that are nonsedating offer promise for control of symptoms without the problem of frequent side effects. PMID- 7887359 TI - Pulmonary lymphangiomyomatosis. AB - Lymphangiomyomatosis is a rare disease of unknown etiology characterized by hamartomatous proliferation of smooth muscle in the pulmonary lymphatics, blood vessels and airways. The disease occurs exclusively in women of reproductive age. Although the clinical course and radiographic findings may strongly suggest lymphangiomyomatosis, definitive diagnosis is made by obtaining open-lung biopsy. The clinical course of lymphangiomyomatosis is progressive, leading to pulmonary insufficiency and death within 10 years. Treatment with hormonal manipulation and/or oophorectomy has resulted in temporary improvement or stabilization of the disease process. PMID- 7887358 TI - Screening for Chlamydia trachomatis infection. AB - Infection with Chlamydia trachomatis can be either symptomatic or asymptomatic. In adults, complications include infertility, chronic pelvic pain and ectopic pregnancy. Complications in newborns include conjunctivitis and pneumonia. Screening of asymptomatic women at high risk for the disease can identify candidates for antibiotic therapy. Until recently, chlamydia cell culture was the only diagnostic test and it was not widely available. Because the specificity of cell culture is 100 percent, it remains the standard against which other tests are measured. The recent development of nonculture tests makes it feasible for most laboratories and physicians' offices to offer testing. The main disadvantage of nonculture tests is low specificity. A positive screening test in a woman at low risk should be confirmed by a second test. Routine screening and treatment of patients who are at high risk can decrease the incidence, complications and transmission of chlamydial infection. PMID- 7887360 TI - Allergic rhinitis. AB - Allergic rhinitis commonly manifests for the first time in childhood or adolescence with seasonal or perennial sneezing, rhinorrhea, nasal congestion, and pruritus of the nose, eyes and throat. The nasal mucosa are pale blue and boggy, with a clear discharge. Patients should be instructed to avoid breathing tobacco smoke, to remove bedroom carpeting, to use foam pillows, to enclose mattresses and box springs in plastic covers, to keep house windows closed and to reduce indoor humidity by using air conditioning. If these avoidance procedures, together with oral and ocular antihistamines and/or decongestants, do not provide relief of symptoms, intranasal corticosteroids and cromolyn may be prescribed. Pharmacotherapy is more effective if it is used prophylactically. Second generation antihistamines may reduce sedative and anticholinergic side effects. Intranasal decongestants should be used for only three to four days. Immunotherapy is appropriate for patients who remain unresponsive to therapy. Intranasal cromolyn should be the first drug considered in the treatment of pregnant women. PMID- 7887361 TI - NSAIDs, antihypertensive agents and loss of blood pressure control. AB - It is common for patients seen by primary care physicians to be taking both nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive agents. If blood pressure control diminishes in these patients, the physician must evaluate the potential interaction between the two classes of medication. Although the increase in blood pressure secondary to NSAID use may be only 5 to 10 mm Hg, this increase may be enough to justify a change in medication. For this reason, it is important to evaluate the interaction between the two types of drugs and determine its clinical significance in specific patients. PMID- 7887362 TI - Adult immunizations--a practical approach for clinicians: Part I. AB - Vaccine-preventable diseases cause needless sickness and death in adult Americans. Most adults 65 years of age or older have not been immunized against influenza or pneumococcal disease. In addition to an age of 65 years or older, indications for influenza and pneumococcal vaccines include chronic obstructive pulmonary disease, hemodynamically significant cardiac disease and infection with the human immunodeficiency virus. Many adults in the United States also are not sufficiently protected against tetanus, diphtheria, measles, mumps and rubella. PMID- 7887364 TI - Significant FDA approvals in 1994. PMID- 7887363 TI - Cancer detection in adults by physical examination. U.S. Public Health Service. PMID- 7887365 TI - ACIP revises typhoid immunization recommendations. PMID- 7887366 TI - AAP releases pediatric vision screening guidelines. American Academy of Pediatrics. PMID- 7887367 TI - FDA addresses childhood iron poisoning. PMID- 7887368 TI - OTC switch considered for asthma. PMID- 7887369 TI - Treating hot flashes. PMID- 7887370 TI - Phases in implementing patient counseling. PMID- 7887371 TI - Treatment options in Parkinson's disease. PMID- 7887372 TI - Treatment of postpartum depression. PMID- 7887373 TI - Factors influencing the delivery of pharmacy services. AB - This study of 590 community pharmacies examined relationships between prescription payment methods and the number of pharmacy services provided at community pharmacies. Also studied were pharmacists' perceptions regarding: (1) the importance of 24 different pharmacy services, (2) the importance of three motivating factors in providing pharmacy services, (3) satisfaction with three methods of payment for pharmacy services, and (4) agreement with factors cited in the literature as barriers to pharmaceutical care. Results revealed a significant positive relationship (p < 0.05) between the number of pharmacy services provided and the percentage of private-pay prescriptions processed. A significant (p < 0.05) inverse relationship was identified between the number of pharmacy services provided and both the percentage of prescriptions processed for third parties other than Medicaid and the percentage of all third party prescriptions processed. Financial incentives were identified as the most important motivator in providing pharmacy services. Private-pay reimbursement was significantly more satisfactory to respondents than Medicaid reimbursement, and both were more satisfactory than reimbursement by a third party other than Medicaid. The greatest perceived barriers to the provision of pharmacy services involved financial and administrative considerations. Results suggest that financial incentives play a critical role in stimulating the provision of pharmacy services. PMID- 7887374 TI - Defining and marketing value added services. PMID- 7887375 TI - Conference focuses on importance of outcomes research. PMID- 7887376 TI - Using liquid medications safely. PMID- 7887377 TI - Effect of platelet glycoprotein IIb/IIIa integrin blockade on activated clotting time during percutaneous transluminal coronary angioplasty or directional atherectomy (the EPIC trial). Evaluation of c7E3 Fab in the Prevention of Ischemic Complications trial. AB - The activated clotting time (ACT) has been used during percutaneous transluminal coronary angioplasty (PTCA) to monitor the extent of thrombin inhibition and anti coagulation from heparin in an attempt to minimize untoward thrombotic events and hemorrhagic complications. With the introduction of potent platelet inhibitors, such as the chimeric monoclonal antibody c7E3, to interventional cardiology, the utility of measuring and regulating procedural ACT has not been examined. To investigate the possible influence of platelet IIb/IIIa antagonism on procedural ACT, we reviewed data from the Evaluation of c7E3 Fab in the Prevention of Ischemic Complications (EPIC) trial. In the EPIC trial, 2,099 patients undergoing PTCA with a high risk of abrupt vessel closure were randomized to receive placebo (n = 696) or the IIb/IIIa platelet receptor antagonist c7E3 Fab (n = 1,403). Despite receiving less procedural heparin, and fewer patients receiving very high heparin doses (> 14,000 U) than the placebo group, those receiving c7E3 had a higher mean (401 vs 367 seconds, p < 0.001) ACT when corrected for body weight. The ACT is increased approximately 35 seconds by the platelet IIb/IIIa receptor antagonist c7E3 Fab. This has important implications for dosing conjunctive heparin therapy and performing PTCA or directional coronary atherectomy in the setting of IIb/IIIa-directed therapy. PMID- 7887378 TI - Accuracy and usefulness of atrial pacing in conjunction with transesophageal echocardiography in the detection of cardiac ischemia (a comparative study with scintigraphic tomography and coronary arteriography). AB - A comparative study of transesophageal echocardiography with single-photon emission computed tomography (SPECT) and coronary arteriography was performed in a community outpatient setting to determine accuracy and feasibility of the technique. Forty-one of 55 patients underwent all 3 procedures within a 90-day period. Fourteen patients underwent only SPECT and were compared with transesophageal echocardiography with pacing (TEEP). Atrial esophageal pacing was performed with transesophageal echocardiography to increase double product and induce ischemia, which would manifest as abnormal wall motion. The results in these patients indicated a sensitivity and specificity of 92% and 87% for TEEP and 96% and 82% for SPECT, respectively, using angiography as the gold standard. In 14 patients, the sensitivity of TEEP using SPECT as standard was 80% and the specificity was 87%. The 1 view that appeared to pick up the highest yield of abnormalities was the transgastric short-axis view. Thus, TEEP is indicated in the detection of chronotropically incompetent patients and those unable to exercise whose transthoracic images are not optimal. It is highly accurate compared with angiography or SPECT. PMID- 7887379 TI - Symptom-limited arm exercise increases detection of ischemia during dipyridamole tomographic thallium stress testing in patients with coronary artery disease. AB - Exercise combined with dipyridamole during thallium stress testing in patients with coronary artery disease (CAD) increases the frequency of angina and ischemic ST changes in the electrocardiogram. Evidence for an increase in thallium abnormalities has been inconclusive. We prospectively examined 54 consecutive patients who underwent coronary angiography and tomographic thallium with dipyridamole (0.57 mg/kg) alone and combined with symptom-limited dynamic arm exercise. Most patients presented with a history of chest pain and 49 had angiographic evidence of significant coronary stenosis (50% diameter narrowing). Thallium abnormalities were scored blindly by consensus. The number of abnormal segments (total and ischemic) and indexes of left ventricular dysfunction, such as increased lung uptake or ischemic dilation, were compared in the 49 patients with CAD. During arm exercise more patients had evidence of ischemia (39 vs 30; p < 0.001), and the number of ischemic segments increased significantly from 1.3 +/ 1.5 to 2.5 +/- 2.2 (p < 0.001). There was also a significant increase in the indexes of left ventricular dysfunction, ischemic dilation (10 vs 4 patients; p < 0.03) and increased lung uptake (16 vs 5 patients; p < 0.001). Patients who exercised had increased thallium evidence of extent and severity of ischemia and more frequent indexes of left ventricular dysfunction. Thus, symptom-limited arm exercise improves detection of extent and severity of ischemia in patients with CAD undergoing dipyridamole thallium stress testing. PMID- 7887380 TI - Comparison of outcome in patients with acute myocardial infarction aged > 75 years with that in younger patients. AB - Despite the advancements in reperfusion therapy, elderly patients with acute myocardial infarction (AMI) continue to have higher mortality and complication rates than younger patients. To evaluate this group we reviewed 994 consecutive patients with AMI at our hospital during a 24-month period. There were 307 patients aged > 75 years and 687 younger patients. Demographic analysis of the 2 groups showed that the elderly had a higher proportion of women (56% vs 31%, p < 0.01), more previous AMI (32% vs 23%, p < 0.01), and a higher incidence of bundle branch block (18% vs 8%, p < 0.01). Only 8% of the elderly and 36% of the younger patients were considered eligible for thrombolysis (p < 0.01). In the elderly, risk of bleeding and late presentation were the most common reasons for exclusion from treatment with thrombolytic therapy. Despite a higher proportion of non-Q wave AMI (56% vs 44%, p < 0.01) in the elderly, the incidence of congestive heart failure (47% vs 23%, p < 0.001) and death (28% vs 11%, p = 0.001) was greater. Causes of death were not significantly different. Increased mortality in the elderly was not due to multisystem failure but to impaired myocardial reserve, suggesting that more aggressive reperfusion strategies may improve prognosis. PMID- 7887381 TI - Gadolinium-enhanced magnetic resonance imaging in acute myocardial infarction. AB - To investigate the clinical application of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) in the management of acute myocardial infarction (AMI), we examined 44 patients with AMI within 1 month after onset. Enhanced images were classified into 4 types: nontransmural (type 1), transmural and homogeneous (type 2), transmural and marginal (type 3), and no enhancement (type 4). Each enhancement pattern was correlated with angiographic and thallium-201 imaging results. The redistribution images of thallium were graded on a 4-point scale from 0 (normal) to 3 (markedly reduced or absent activity). The percentage of the perimeter affected by asynergy was obtained from the left ventriculogram. Peak creatine kinase and the percentage of asynergic perimeter were significantly higher in type 3 than in other type patients. End-diastolic volume index was significantly higher in type 3 than in type 2 patients. Left ventricular ejection fraction was lowest, and end-systolic volume index, thallium-201 score, and incidence of wall thinning on MRI were highest in type 3 patients. Therefore, the transmural and marginal enhancement pattern (type 3) was compatible with extensive myocardial infarction with infarct expansion and less viable myocardium. In the other types, the infarction was small to moderate in size and left ventricular function was well preserved. Thus, Gd-DTPA-enhanced MRI may be useful in the evaluation of left ventricular function and myocardial viability of the infarct region after AMI. PMID- 7887382 TI - Effects of pravastatin on cardiovascular reactivity to norepinephrine and angiotensin II in patients with hypercholesterolemia and systemic hypertension. AB - This study was conducted to examine the effects of short-term cholesterol reduction on cardiovascular reactivity in mildly hypertensive patients. Seven male and 7 female patients, aged 34 to 68 years, received pravastatin (40 mg/day) or matched placebo for 3 weeks in a randomized, double-blind, crossover study. Cardiovascular reactivity was assessed by measurement of blood pressure (BP) responses to incremental infusions of angiotensin II and norepinephrine, by cold pressor testing and isometric exercise. Compared with placebo, pravastatin caused significant reductions in plasma total and low-density lipoprotein cholesterol levels, which averaged 20% and 31%, respectively (both p < 0.0001), and in diastolic BP responses (expressed as the infusion rate required to raise BP by 20 mm Hg) to both angiotensin II (7.3 +/- 3.0 vs 9.7 +/- 4.7 ng/kg/min, p = 0.05) and norepinephrine (0.15 +/- 0.13 vs 0.38 +/- 0.33 micrograms/kg/min, p = 0.03). Systolic BP responses were similar with both treatments. Body weight, resting BP, and maximal BP responses to physical stressors were similar with each treatment. PMID- 7887383 TI - The learning curve for radiofrequency ablation of tachyarrhythmias in pediatric patients. Participating members of the Pediatric Electrophysiology Society. AB - The results of radiofrequency ablation for treatment of supraventricular tachyarrhythmias have been reported to improve with increasing experience; however, the precise nature of the learning curve in children is unknown. From November 1990 to October 1993, 1,546 consecutive procedures from the Pediatric Radiofrequency Ablation Registry were categorized into deciles based on number of prior pediatric procedures at the submitting institution. Negative exponential models were tested for strength of relation between volume of prior experience and 4 measures of outcome: success rate, complication rate, fluoroscopy time, and procedure time. Negative exponential curves described the experience-outcome relations well (r = 0.81 to 0.97). Learning rates were most rapid for successful ablation of left free wall accessory pathways, and slowest for right free wall pathway ablation. These models suggest that, given enough experience, procedural success rates > 90% (regardless of pathway location) and fluoroscopy and procedure times averaging < 40 minutes and 250 minutes, respectively, can be achieved in pediatric patients. PMID- 7887384 TI - Failure to decrease parasympathetic tone during upright tilt predicts a positive tilt-table test. AB - The most frequently proposed mechanism for vasodepressor syncope is based on cardiac mechanoreceptor activation by augmented sympathetic tone. Because of the central role of the autonomic nervous system in this response, we hypothesized that the responses of the sympathetic and parasympathetic nervous systems (as assessed by analysis of heart rate variability) to orthostatic stress would differentiate patients with a positive from those with a negative tilt-table response. We therefore evaluated 28 patients undergoing tilt-table testing for presumed vasodepressor syncope. Based on 5-minute electrocardiographic samples obtained during the supine and upright phases (without isoproterenol infusion), we computed the mean RR interval, reflecting integrated cardiac sympathetic and parasympathetic tone, as well as the root-mean-square of successive differences of the RR intervals (RMSSD), a measure of high-frequency heart rate variability that is correlated with parasympathetic tone. Eleven patients had a negative and 17 a positive tilt response. There were no differences between the groups at baseline. In response to upright tilt, the mean RR decreased by a similar magnitude in both groups. In contrast, RMSSD decreased by 36% (p = 0.05) in response to upright tilt in patients with a negative response, but did not change significantly in patients with a positive tilt response. Absence of a decrease in RMSSD in response to orthostatic stress had 100% specificity and 41% sensitivity for predicting a positive test result. Thus, failure of withdrawal of parasympathetic tone (as assessed by RMSSD) during upright tilt predicts a positive tilt response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887386 TI - Percutaneous mitral balloon valvotomy for recurrent mitral stenosis after surgical commissurotomy. AB - Immediate outcome and 4-year follow-up results of percutaneous mitral balloon valvotomy (PMV) in patients with previous surgical mitral commissurotomy are studied. Repeat surgical mitral commissurotomy in patients with previous surgical commissurotomy is associated with higher mortality and morbidity. PMV has been proven to be safe and could be an ideal alternative in this patient group. The results of 68 patients with previous surgical commissurotomy were compared with those of 261 patients without prior surgical intervention. A good outcome, defined as the final mitral valve area > 1.5 cm2, was obtained in 51% of the patients with prior surgical commissurotomy compared with 71% in the control group (p = 0.002). During the 4-year follow-up period, there were more patients who required mitral valve replacement (19% vs 7%; p = 0.004) and who were in New York Heart Association functional class III and IV (85% vs 71%; p = 0.02) among those with prior surgical commissurotomy. However, when these patients were divided according to echocardiographic score, those with a score < or = 8 had immediate outcome and long-term results similar to those without prior commissurotomy. PMV can be performed safely in patients with prior surgical commissurotomy. Although results of long-term follow-up in these patients is not as good as those in patients without prior surgical commissurotomy, those with a low echocardiographic score had similar excellent long-term results. PMID- 7887385 TI - Effects of fosinopril on exercise tolerance and clinical deterioration in patients with chronic congestive heart failure not taking digitalis. Fosinopril Heart Failure Study Group. AB - A total of 241 men and women with mild to moderately severe chronic heart failure (New York Heart Association functional class II [90%] or III) and a mean (+/- SD) left ventricular ejection fraction of 25 +/- 7%, entered a 24-week, prospective, double-blind, placebo-controlled trial of 10 or 20 mg/day of fosinopril, a phosphinic acid angiotensin-converting enzyme inhibitor. Patients received concomitant diuretic therapy but not digitalis. Primary end points were mean change in maximal treadmill exercise time and occurrence of prospectively defined clinical events indicative of worsening heart failure (most to least severe): death, withdrawal for worsening heart failure, hospitalization for worsening heart failure, need for supplemental diuretic or emergency room visit for worsening heart failure, and no event. At study end point, treadmill exercise time had improved in the fosinopril versus the placebo group (+28.4 vs -13.5 seconds, p = 0.047). New York Heart Association functional class had improved at end point more frequently (24% vs 13%) and deteriorated less frequently (18% vs 32%) in the fosinopril group (p = 0.003). More patients treated with fosinopril (66% vs 50%) remained free of clinical events indicative of worsening heart failure, and fosinopril-treated patients had less severe clinical events (p = 0.004). Dyspnea, fatigue, and paroxysmal nocturnal dyspnea improved more often and worsened less often in this group (p < or = 0.002), and edema showed a trend toward improvement (p = 0.088). These clinical benefits did not require concomitant digitalis therapy. Fosinopril was associated with an acceptable safety profile. PMID- 7887387 TI - Abnormal Doppler pulmonary venous flow patterns in children after repaired total anomalous pulmonary venous connection. AB - Doppler echocardiography was used to evaluate pulmonary venous flow patterns in 16 children with repaired total anomalous pulmonary venous connection and in 16 age-matched normal controls. Using right upper pulmonary venous pulsed Doppler tracings, peak velocities and velocity time integrals were determined for ventricular systole, ventricular diastole, and atrial systole. Mitral inflow indexes and cardiac outputs were obtained. Patients with repaired total anomalous pulmonary venous connection and controls were similar in weight, heart rate, mitral inflow indexes, and cardiac output. In normal children, peak velocities were greater during ventricular diastole than systole, but velocity time integrals were greater during ventricular systole than diastole. Compared with normals, repaired patients had unobstructed flow patterns with increased peak velocities during ventricular diastole (0.92 +/- 0.35 vs 0.62 +/- 0.12 m/s) and atrial systole (0.27 +/- 0.12 vs 0.17 +/- 0.04 m/s). Velocity time integrals of repaired patients were increased during atrial systole (0.02 +/- 0.01 vs 0.01 +/- 0.03 m) but decreased during ventricular systole (0.08 +/- 0.03 vs 0.12 +/- 0.03 m). Systolic-to-diastolic ratios were decreased in repaired patients for peak velocity (0.56 +/- 0.20 vs 0.79 +/- 0.12) and velocity time integral (0.6 +/- 0.18 vs 1.48 +/- 0.35). Thus, pulmonary venous flow in normal children is greater during ventricular systole than during ventricular diastole. Repaired patients show a shift in forward flow from ventricular systole to diastole, with greater reversed flow during atrial systole. PMID- 7887388 TI - Comparison of four Doppler echocardiographic methods for calculating pulmonary-to systemic shunt flow ratios in patients with ventricular septal defect. AB - Several methods currently exist for quantifying pulmonary (Qp) and systemic (Qs) shunt flow using Doppler echocardiography, although none is widely utilized. In this study, 39 patients (age 2 months to 12 years, mean 2.1 years) underwent an echocardiographic examination within 1 month of Qp:Qs shunt flow determination by oximetry at catheterization. Qp:Qs was determined by 4 methods that utilized: (1) velocity time integrals and luminal areas to estimate volume flow of the pulmonary artery and aorta; (2) the square of the ratios of pulmonary artery to aorta, multiplied by the ratio of pulmonary to aortic peak flow velocities; (3) inclusion of mitral and tricuspid valve volume flow to pulmonary and aortic volume flow; and (4) ventricular septal defect (VSD) diameter and velocity time integral to calculate left-to-right shunt, which, when added to aortic volume flow (Qs), can be used to estimate Qp. Each of the first 3 methods was statistically correlated to the oximetry Qp:Qs, with r values ranging from 0.54 to 0.66 (p < 0.001). However, the fourth method, based on direct computation of flow across the VSD, had the best correlation to catheterization data (r = 0.82), and further improved when 7 patients with a large VSD (> 9 mm/m2), all of whom had bidirectional shunting, were removed (r = 0.90). Thus, we concluded that this latter method demonstrated the best correlation to catheterization-derived shunt flow data, and because this method is somewhat less labor-intensive than the others, should provide clinically useful data well suited for serial evaluation in infants and children with VSD. PMID- 7887389 TI - Effects of previous angina pectoris in patients with first acute myocardial infarction not receiving thrombolytics. MILIS Study Group. Multicenter Investigation of the Limitation of Infarct Size. PMID- 7887390 TI - An electrocardiographic acuteness score for quantifying the timing of a myocardial infarction to guide decisions regarding reperfusion therapy. PMID- 7887391 TI - Long-term follow-up in patients with positive exercise test and angiographically normal coronary arteries (syndrome X). PMID- 7887392 TI - Baseline characteristics in the Cholesterol and Recurrent Events (CARE) trial of secondary prevention in patients with average serum cholesterol levels. PMID- 7887393 TI - Temporal dependence of the return of atrial mechanical function on the mode of cardioversion of atrial fibrillation to sinus rhythm. PMID- 7887394 TI - Significance of cycle length alternation during orthodromic atrioventricular reentrant tachycardia. PMID- 7887395 TI - Effect of residual slow pathway function on the time course of recurrences of atrioventricular nodal reentrant tachycardia after radiofrequency ablation of the slow pathway. PMID- 7887396 TI - Peripheral thyroid hormone metabolism in patients with complex ventricular arrhythmias. PMID- 7887397 TI - Mitral balloon valvuloplasty in patients > 70 years of age with severe mitral stenosis. PMID- 7887398 TI - Progression of asymptomatic aortic stenosis identified in the neonatal period. PMID- 7887399 TI - Midterm outcome after pulmonary balloon valvuloplasty in patients younger than one year of age. PMID- 7887400 TI - Quantitation of left-to-right shunts in secundum atrial septal defect by two dimensional contrast echocardiography with use of Albunex. PMID- 7887401 TI - Two-dimensional and Doppler ultrasound evaluation of femoral arteries in infants after cardiac catheterization. PMID- 7887402 TI - Left ventricular function analyzed by Doppler and echocardiographic methods in short-term hypothyroidism. PMID- 7887403 TI - Comparison of lovastatin and bezafibrate on lipoprotein(a) plasma levels in cardiac transplant recipients. AB - Our results suggest that bezafibrate may be useful in the treatment of high Lp(a) levels in heart transplant patients. PMID- 7887404 TI - Coronary sinus catheterization via a femoral vein. PMID- 7887405 TI - Femoral vein approach to the coronary sinus during electrophysiology studies. PMID- 7887406 TI - Precordial honk due to tricuspid regurgitation. PMID- 7887407 TI - Q-wave infarcts inadequately represented by 12-lead electrocardiograms. PMID- 7887408 TI - Pyruvate dehydrogenase E1 alpha deficiency: males and females differ yet again. PMID- 7887409 TI - Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase: exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex. AB - Human pyruvate dehydrogenase (PDH)-complex deficiency is an inborn error of metabolism that is extremely heterogeneous in its presentation and clinical course. In a study of 14 patients (7 females and 7 males), we have found a mutation in the coding region of the E1 alpha gene in all 14 patients. Two female patients had the same 7-bp deletion at nt 927; another female patient had a 3-bp deletion at nt 931. Another female patient was found to have a deletion of exon 6 in her cDNA. Two other female patients were found to have insertions, one of 13 bp at nt 981 and one of 46 bp at nucleotide 1078. Two male patients were found to have a 4-bp insertion at nucleotide 1163. The remaining six patients all had missense mutations. A male patient and a female patient both had an A1133G mutation. The other missense mutations were C214T, C615A, and C787G (two patients). Five of these mutations are novel mutations, five have been previously reported in other patients, and two were published observations in other patients in an E1 alpha-mutation summary. In the four cases where parent DNA was available, only one mother was found to be a carrier of the same mutation as her child. PMID- 7887411 TI - An intragenic deletion of the P gene is the common mutation causing tyrosinase positive oculocutaneous albinism in southern African Negroids. AB - Tyrosinase-positive oculocutaneous albinism (OCA2), an autosomal recessive disorder of the melanin biosynthetic pathway, is the most common recessive disorder occurring in southern African Bantu-speaking Negroids, with an overall prevalence of 1/3,900. The OCA2 gene, P, has been mapped to chromosome 15q11-q13, and recently alterations in the P gene have been identified in OCA2 individuals. An intragenic deletion has been described and proposed to be of African origin because of its occurrence in four unrelated African American OCA2 individuals and in two individuals, one from Zaire and the other from Cameroon. This study shows that the intragenic deletion is a common cause of OCA2 in southern African Negroids (114/146 [.78]; OCA2 chromosomes) and is associated with one common haplotype (43/55 [.78]; OCA2 chromosomes), confirming the African origin of this allele. On the basis of haplotype data, it would appear that at least seven additional, less frequent OCA2 mutations occur in this population. PMID- 7887410 TI - Similar splicing mutations of the Menkes/mottled copper-transporting ATPase gene in occipital horn syndrome and the blotchy mouse. AB - The connective-tissue disorder occipital horn syndrome (OHS) is hypothesized to be allelic to Menkes disease. The two diseases have different clinical presentations but have a similar abnormality of copper transport. Mice hemizygous for the blotchy allele of the X-linked mottled locus have similar connective tissue defects as OHS and may represent a mouse model of this disease. We have analyzed the Menkes/mottled copper-transporting ATPase in these two potentially homologous disorders and have identified similar splicing mutations in both. Some expression of normal mRNA was detectable by reverse transcription-PCR in the mutant tissues. These findings contrast with the more debilitating mutations observed in Menkes disease and suggest that low amounts of an otherwise normal protein product could result in the relatively mild phenotype of OHS and of the blotchy mouse. PMID- 7887412 TI - Identification of new mutations in the Cu/Zn superoxide dismutase gene of patients with familial amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting motor neurons. Although most cases of ALS are sporadic, approximately 10% are inherited as an autosomal dominant trait. Mutations in the Cu/Zn superoxide dismutase gene (SOD 1) are responsible for a fraction of familial ALS (FALS). Screening our FALS kindreds by SSCP, we have identified mutations in 15 families, of which 9 have not been previously reported. Two of the new mutations alter amino acids that have never been implicated in FALS. One of them affects a highly conserved amino acid involved in dimer contact, and the other one affects the active-site loop of the enzyme. These two mutations reduce significantly SOD 1 enzyme activity in lymphoblasts. Our results suggest that SOD 1 mutations are responsible for > or = 13% of FALS cases. PMID- 7887413 TI - Molecular diagnosis of mucopolysaccharidosis type II (Hunter syndrome) by automated sequencing and computer-assisted interpretation: toward mutation mapping of the iduronate-2-sulfatase gene. AB - Virtually all mutations causing Hunter syndrome (mucopolysaccharidosis type II) are expected to be new mutations. Therefore, as a means of molecular diagnosis, we developed a rapid method to sequence the entire iduronate-2-sulfatase (IDS) coding region. PCR amplicons representing the IDS cDNA were sequenced with an automatic instrument, and output was analyzed by computer-assisted interpretation of tracings, using Staden programs on a Sun computer. Mutations were found in 10 of 11 patients studied. Unique missense mutations were identified in five patients: H229Y (685C-->T, severe phenotype); P358R (1073C-->G, severe); R468W (1402C-->T, mild); P469H (1406C-->A, mild); and Y523C (1568A-->G, mild). Non sense mutations were identified in two patients: R172X (514C-->T, severe) and Q389X (1165C-->T, severe). Two other patients with severe disease had insertions of 1 and 14 bp, in exons 3 and 6, respectively. In another patient with severe disease, the predominant (> 95%) IDS message resulted from aberrant splicing, which skipped exon 3. In this last case, consensus sequences for splice sites in exon 3 were intact, but a 395 C-->G mutation was identified 24 bp upstream from the 3' splice site of exon 3. This mutation created a cryptic 5' splice site with a better consensus sequence for 5' splice sites than the natural 5' splice site of intron 3. A minor population of the IDS message was processed by using this cryptic splice site; however, no correctly spliced message was detected in leukocytes from this patient. The mutational topology of the IDS gene is presented. PMID- 7887414 TI - Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome. AB - Germ-line mutations of the tumor-suppressor gene p53 have been observed in some families with the Li-Fraumeni syndrome (LFS), a familial cancer syndrome in which affected relatives develop a diverse set of early-onset malignancies including breast carcinoma, sarcomas, and brain tumors. The analysis of the p53 gene in LFS families has been limited, in most studies to date, to the region between exon 5 and exon 9. In order to determine the frequency and distribution of germ-line p53 mutations in LFS, we sequenced the 10 coding exons of the p53 gene in lymphocytes and fibroblast cell lines derived from 15 families with the syndrome. Germ-line mutations were observed in eight families. Six mutations were missense mutations located between exons 5 and 8. One mutation was a nonsense mutation in exon 6, and one mutation was a splicing mutation in intron 4, generating aberrant shorter p53 RNA(s). In three families, a mutation of the p53 gene was observed in the fibroblast cell line derived from the proband. However, the mutation was not found in affected relatives in two families and in the blood from the one individual, indicating that the mutation probably occurred during cell culture in vitro. In four families, no mutation was observed. This study indicates that germ line p53 mutations in LFS are mostly located between exons 5 and 8 and that approximately 50% of patients with LFS have no germ-line mutations in the coding region of the p53 gene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887415 TI - Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V. AB - We discovered the missense mutation, A226V, in the ornithine-delta aminotransferase (OAT) genes of two unrelated patients with gyrate atrophy of the choroid and retina (GA). One patient, who was a compound for A226V and for the premature termination allele R398ter, showed a significant (P < .01) decrease in mean plasma ornithine levels, following pyridoxine supplementation with a constant protein intake: 826 +/- 128 microM (n = 5; no pyridoxine supplementation) versus 504 +/- 112 microM (n = 6; 500 mg pyridoxine/d) and 546 +/- 19 microM (n = 6; 1,000 mg pyridoxine/d). In extracts of fibroblasts from a second GA patient homozygous for A226V and from Chinese hamster ovary cells expressing an OAT-cDNA-containing A226V, we found that OAT activity increased from undetectable levels to approximately 10% of normal when the concentration of pyridoxal phosphate was increased from 50 to 600 microM. A226V is the fourth disease-causing pyridoxine-responsive human mutation to be reported. PMID- 7887416 TI - Galactosemia: a strategy to identify new biochemical phenotypes and molecular genotypes. AB - We describe a stratagem for identifying new mutations in the galactose-1 phosphate uridyl transferase (GALT) gene. GALT enzyme activity and isoforms were defined in erythrocytes from probands and their first-degree relatives. If the biochemical phenotypes segregated in an autosomal recessive pattern, we screened for common mutations by using multiplex PCR and restriction endonuclease digestions. If common mutant alleles were not present, the 11 exons of the GALT gene were amplified by PCR, and variations from the normal nucleotide sequences were identified by SSCP. The suspected region(s) was then analyzed by direct DNA sequencing. We identified 86 mutant GALT alleles that reduced erythrocyte GALT activity. Seventy-five of these GALT genomes had abnormal SSCP patterns, of which 41 were sequenced, yielding 12 new and 21 previously reported, rare mutations. Among the novel group of 12 new mutations, an unusual biochemical phenotype was found in a family whose newborn proband has classical galactosemia. He had inherited two mutations in cis (N314D-E203K) from his father, whose GALT activity was near normal, and an additional GALT mutation in the splice-acceptor site of intron C (IVSC) from his mother. The substitution of a positively charged E203K mutation created a unique isoform-banding pattern. An asymptomatic sister's GALT genes carries three mutations (E203K-N314D/N314D) with eight distinct isoform bands. Surprisingly, her erythrocytes have normal GALT activity. We conclude that the synergism of pedigree, biochemical, SSCP, and direct GALT gene analyses is an efficient protocol for identifying new mutations and speculate that E203K and N314D codon changes produce intraallelic complementation when in cis. PMID- 7887417 TI - Identification and functional analysis of three distinct mutations in the human galactose-1-phosphate uridyltransferase gene associated with galactosemia in a single family. AB - We have identified three mutations associated with transferase-deficiency galactosemia in a three-generation family including affected members in two generations and have modeled all three mutations in a yeast-expression system. A sequence of pedigree, biochemical, and molecular analyses of the galactose-1 phosphate uridyltransferase (GALT) enzyme and genetic locus in both affected and carrier individuals revealed three distinct base substitutions in this family, two (Q188R and S135L) that had been reported previously and one (V151A) that was novel. Biochemical analyses of red-blood-cell lysates from the relevant family members suggested that each of these mutations was associated with dramatic impairment of GALT activity in these cells. While this observation was consistent with our previous findings concerning the Q188R mutation expressed both in humans and in a yeast-model system, it was at odds with a report by Reichardt and colleagues, indicating that in their COS cell-expression system the S135L substitution behaved as a neural polymorphism. To address this apparent paradox, as well as to investigate the functional significance of the newly identified V151A substitution, all three mutations were recreated by site-directed mutagenesis of the otherwise wild-type human GALT sequence and were expressed both individually and in the appropriate allelic combinations in a GALT-deficient strain of the yeast Saccharomyces cerevisiae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887418 TI - Studies of X inactivation and isodisomy in twins provide further evidence that the X chromosome is not involved in Rett syndrome. AB - Rett syndrome (RS), a progressive encephalopathy with onset in infancy, has been attributed to an X-linked mutation, mainly on the basis of its occurrence almost exclusively in females and its concordance in female MZ twins. The underlying mechanisms proposed are an X-linked dominant mutation with male lethality, uniparental disomy of the X chromosome, and/or some disturbance in the process of X inactivation leading to unequal distributions of cells expressing maternal or paternal alleles (referred to as a "nonrandom" or "skewed" pattern of X inactivation). To determine if the X chromosome is in fact involved in RS, we studied a group of affected females including three pairs of MZ twins, two concordant for RS and one uniquely discordant for RS. Analysis of X-inactivation patterns confirms the frequent nonrandom X inactivation previously observed in MZ twins but indicates that this is independent of RS. Analysis of 29 RS females reveals not one instance of uniparental X disomy, extending the observations previously reported. Therefore, our findings contribute no support for the hypothesis that RS is an X-linked disorder. Furthermore, the concordant phenotype in most MZ female twins with RS, which has not been observed in female twins with known X-linked mutations, argues against an X mutation. PMID- 7887419 TI - Batten disease gene, CLN3: linkage disequilibrium mapping in the Finnish population, and analysis of European haplotypes. AB - The gene for Batten disease (juvenile-onset neuronal ceroid lipofuscinosis, or Spielmeyer-Sjogren disease), CLN3, maps to 16p11.2-12.1. Four microsatellite markers--D16S288, D16S299, D16S298, and SPN--are in strong linkage disequilibrium with CLN3 in 142 families from 16 different countries. These markers span a candidate region of approximately 2.1 cM. CLN3 is most prevalent in northern European populations and is especially enriched in the isolated Finnish population, with an incidence of 1:21,000. Linkage disequilibrium mapping was applied to further refine the localization of CLN3 in 27 Finnish families by using linkage disequilibrium data and information about the population history of Finland to estimate the distance of the closest markers from CLN3. CLN3 is predicted to lie 8.8 kb (range 6.3-13.8 kb) from D16S298 and 165.4 kb (132.4 218.1 kb) from D16S299. Enrichment of allele "6" at D16S298 (on 96% of Finnish and 92% of European CLN3 chromosomes) provides strong evidence that the same major mutation is responsible for Batten disease in Finland as in most other European countries and that it is therefore not a Finnish mutation. Genealogical studies show that Batten disease is widespread throughout the densely populated regions of Finland. The ancestors of two Finnish patients carrying rare alleles "3" and "5" at D16S298 in heterozygous form originate from the southwestern coast of Finland, and these probably represent other foreign mutations. Analysis of the number and distribution of CLN3 haplotypes from 12 European countries provides evidence that more than one mutation has arisen in Europe. PMID- 7887420 TI - Chromosome 16 microdeletion in a patient with juvenile neuronal ceroid lipofuscinosis (Batten disease). AB - The gene that is involved in juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease--CLN3--has been localized to 16p12, and the mutation shows a strong association with alleles of microsatellite markers D16S298, D16S299, and D16S288. Recently, haplotype analysis of a Batten patient from a consanguineous relationship indicated homozygosity for a D16S298 null allele. PCR analysis with different primers on DNA from the patient and his family suggests the presence of a cytogenetically undetectable deletion, which was confirmed by Southern blot analysis. The microdeletion is embedded in a region containing chromosome 16 specific repeated sequences. However, putative candidates for CLN3, members of the highly homologous sulfotransferase gene family, which are also present in this region in several copies, were not deleted in the patient. If the microdeletion in this patient is responsible for Batten disease, then we conclude that the sulfotransferase genes are probably not involved in JNCL. By use of markers and probes flanking D16S298, the maximum size of the microdeletion was determined to be approximately 29 kb. The microdeletion may affect the CLN3 gene, which is expected to be in close proximity to D16S298. PMID- 7887421 TI - Trisomy 18: studies of the parent and cell division of origin and the effect of aberrant recombination on nondisjunction. AB - We have studied the mechanism of origin of 63 cases of trisomy 18. In 2 the additional chromosome was paternal in origin, and in the remaining 61 it was maternal in origin. Both paternal cases were attributable to a postzygotic mitotic (PZM) error. Among the 54 maternal cases for which the cell division of error was established, only 16 were attributable to an error at the first meiotic division (mat MI), whereas no fewer than 35 were due to an error at the second meiotic division (mat MII), the remaining 3 being the result of a PZM error involving the maternal chromosome 18. A standard map of chromosome 18 was constructed and compared with the nondisjunctional map. Approximately one-third of the mat MI errors were associated with complete absence of recombination, whereas in the remaining two-thirds and in all the mat MII errors recombination in the nondisjoined chromosomes appeared to be normal. All the maternal errors were associated with an increased maternal age, although this reached significance only for the mat MII category of nondisjunction. Our observations on chromosome 18 are compared with those on other chromosomes for which there are comparable data. PMID- 7887422 TI - Clinical and molecular characterization of patients with distal 11q deletions. AB - Jacobsen syndrome is caused by segmental aneusomy for the distal end of the long arm of chromosome 11. Typical features include mild to moderate psychomotor retardation, trigonocephaly, facial dysmorphism, cardiac defects, and thrombocytopenia, though none of these features are invariably present. To define the critical regions responsible for these abnormalities, we studied 17 individuals with de novo terminal deletions of 11q. The patients were characterized in a loss-of-heterozygosity analysis using polymorphic dinucleotide repeats. The breakpoints in the complete two-generation families were localized with an average resolution of 3.9 cM. Eight patients with the largest deletions extending from 11q23.3 to 11qter have breakpoints, between D11S924 and D11S1341. This cytogenetic region accounts for the majority of 11q- patients and may be related to the FRA11B fragile site in 11q23.3. One patient with a small terminal deletion distal to D11S1351 had facial dysmorphism, cardiac defects, and thrombocytopenia, suggesting that the genes responsible for these features may lie distal to D11S1351. Twelve of 15 patients with deletion breakpoints as far distal as D11S1345 had trigonocephaly, while patients with deletions distal to D11S912 did not, suggesting that, if hemizygosity for a single gene is responsible for this dysmorphic feature, the gene may lie distal to D11S1345 and proximal to D11S912. PMID- 7887423 TI - Mapping of a further malignant hyperthermia susceptibility locus to chromosome 3q13.1. AB - Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disease for which MH susceptibility (MHS) is transmitted as an autosomal dominant trait. A potentially life-threatening MH crisis is triggered by exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants. The first malignant hyperthermia susceptibility locus (MHS1) was identified on human chromosome 19q13.1, and evidence has been obtained that defects in the gene for the calcium release channel of skeletal muscle sarcoplasmic reticulum (ryanodine receptor; RYR1) can cause some forms of MH. However, MH has been shown to be genetically heterogeneous, and additional loci on chromosomes 17q and 7q have been suggested. In a collaborative search of the human genome with polymorphic microsatellite markers, we now found linkage of the MHS phenotype, as assessed by the European in vitro contracture test protocol, to markers defining a 1-cM interval on chromosome 3q13.1. A maximum multipoint lod score of 3.22 was obtained in a single German pedigree with classical MH, and none of the other pedigrees investigated in this study showed linkage to this region. Linkage to both MHS1/RYR1 and putative loci on chromosome 17q and 7q were excluded. This study supports the view that considerable genetic heterogeneity exists in MH. PMID- 7887424 TI - Linkage of early-onset osteoarthritis and chondrocalcinosis to human chromosome 8q. AB - Calcium pyrophosphate-deposition disease (CPDD), also called "chondrocalcinosis" or "pseudogout," is a disorder characterized by the deposition of calcium containing crystals in joint tissue, which leads to arthritis-like symptoms. The presence of these crystals in joint tissue is a common finding in the elderly, and, in this population, there is a poor correlation with joint pain. In contrast, early-onset CPDD has been described in several large families in which the disease progresses to severe degenerative osteoarthritis (OA). In these families, an autosomal dominant mode of inheritance is observed, with an age at onset between the 2d and 5th decades of life. In this report, we describe a large New England family with early-onset CPDD and severe degenerative OA. We found genetic linkage between the disease in this family and chromosome 8q, with a multipoint lod score of 4.06. These results suggest that a defective gene at this location causes the disease in this family. PMID- 7887425 TI - Genetic heterogeneity in multiple epiphyseal dysplasia. AB - Multiple epiphyseal dysplasia (MED) comprises a group of hereditary chondrodysplasias in which there are major anatomic abnormalities of the long tubular bones. The Fairbank and Ribbing types are the most frequently cited types of MED. They are primarily defined radiographically and are autosomal dominant conditions. Recently, MED in one family was shown to map to the pericentromeric region of chromosome 19 and is probably allelic to pseudoachondroplasia. We have tested linkage with six short tandem repeat markers from chromosome 19 to autosomal dominant MED in one four-generation family and to MED in a unique family with three of seven siblings affected and with unaffected parents. Autosomal dominant MED in family 1 was linked with a maximum LOD score, at D19S212, of 3.22 at a recombination fraction (theta) of .00. Linkage to chromosome 19 was excluded with MED in the other family, under both autosomal recessive and autosomal dominant, with either reduced-penetrance or germ line mosaicism models. Linkage to candidate genes COL9A1, COL9A2, and COL11A2 was tested and excluded for both genetic models in this family. COL11A1 was excluded under a recessive model. We have confirmed linkage of autosomal dominant Fairbank MED to chromosome 19 and have demonstrated that MED is genetically heterogeneous. PMID- 7887426 TI - Deletion and translocation of chromosome 11q13 sequences in cervical carcinoma cell lines. AB - Molecular genetic studies on HeLa cell-derived nontumorigenic and tumorigenic hybrids have previously localized the HeLa cell tumor-suppressor gene to the long arm of chromosome 11. Extensive molecular and cytogenetic studies on HeLa cells have shown chromosome band 11q13 to be rearranged in this cell line. To determine whether q13 rearrangement is a nonrandom event in cervical carcinomas, six different human papilloma virus (HPV)-positive (HeLa, SiHa, Caski, C4-I, Me180, and Ms751) and two different HPV-negative (C33A and HT3) cell lines were studied. Long-range restriction mapping using a number of q13-specific probes showed molecular rearrangements within 75 kb of INT2 probe in three HPV-positive cell lines (HeLa, SiHa, and Caski) and in an HPV-negative cell line (HT3). FISH using an INT2 YAC identified a breakpoint within the sequences spanned by this YAC in two of the cell lines, HeLa and Caski. INT2 cosmid derived from this YAC showed deletion of cosmid sequences in two other cell lines, SiHa and C33A. These two cell lines, however, retained cosmid sequences of Cyclin D1, a probe localized 100 kb proximal to INT2. Deletions being the hallmark of a tumor-suppressor gene, we conclude that the 100-kb interval between the two cosmids might contain sequences of the cervical carcinoma tumor-suppressor gene. PMID- 7887427 TI - The molecular basis of HEXA mRNA deficiency caused by the most common Tay-Sachs disease mutation. AB - Tay-Sachs disease (TSD) is a catastrophic neurodegenerative disorder caused by mutations in the HEXA gene. The most common TSD allele worldwide contains a 4-bp insertion in exon 11 that produces a downstream premature termination codon. Despite normal transcription of this allele, HEXA mRNA is severely reduced, indicating that the HEXA transcript must be unstable. Minigenes of HEXA were constructed and expressed in mouse L cells, to investigate the relationship between the 4-bp insertion and mRNA deficiency. We conclude that the mRNA instability is caused by the premature termination codon and not by a cryptic mutation or by the 4-bp insertion directly and that degradation occurs coincident with or after splicing. PMID- 7887428 TI - Characterization of revertant muscle fibers in Duchenne muscular dystrophy, using exon-specific monoclonal antibodies against dystrophin. AB - Most Duchenne muscular dystrophy (DMD) patients have genetic deletions or point mutations in the dystrophin gene that alter the reading frame of dystrophin mRNA. This causes early termination of translation, and no dystrophin (or, less commonly, a truncated N-terminal dystrophin fragment) is produced. In many DMD patients, however, a small proportion of muscle fibers show strong dystrophin staining, and these "revertant fibers" are thought to arise by a mechanism that restores the reading frame. Exon-specific monoclonal antibodies (mAbs) have now been used to determine, for the first time, which exons are removed, in order to correct the reading frame in individual muscle fibers. Thus, 15 revertant fibers in a DMD patient with a frameshift deletion of exon 45 were shown to correct the frameshift by the additional deletion of exon 44 (or perhaps exon 46 in some fibers) from the dystrophin mRNA, but not by larger deletions. This result was consistent with reverse transcription (RT)-PCR and sequencing of a minor dystrophin mRNA with an exon 43/46 junction in this biopsy. In a DMD patient with a frameshift deletion of exons 42 and 43, however, larger deletions than the minimum necessary were used to correct the frameshift. In this patient, who produces a half-size N-terminal dystrophin fragment in all fibers, we were able to show that the revertant dystrophin replaces the truncated dystrophin in revertant-fiber sarcolemma. The results are consistent with somatic mutations in revertant-fiber nuclei, which result in removal of additional exons from dystrophin mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887429 TI - Prospective assessment of risks for cervicomedullary-junction compression in infants with achondroplasia. AB - Achondroplasia, the most common heritable skeletal dysplasia, may result in abnormality at the craniocervical junction, which is a potentially lethal problem in a subset of young infants with this disorder. We evaluated and followed an unbiased and unselected consecutive series of infants with achondroplasia, to better document the occurrence, frequency, and clinical presentation of craniocervical abnormalities. Of 53 prospectively ascertained infants, 5 were judged to have sufficient craniocervical junction compression to require surgical decompression. Intraoperative observation always showed marked abnormality of the cervical spinal cord, and all operated-on children showed marked improvement of neurological function. The most frequent clinical abnormalities within this subset were those expected for high cervical myelopathy. The best predictors of need for suboccipital decompression included lower-limb hyperreflexia or clonus, on examination; central hypopnea demonstrated by polysomnography; and foramen magnum measures below the means for children with achondroplasia. Infants with achondroplasia are at risk for potentially lethal sequelae of craniocervical junction abnormalities; selective intervention can be life and health saving, but individuals at high risk will be identified only if all affected infants undergo comprehensive assessment in infancy. PMID- 7887430 TI - Recommendations for standardized human pedigree nomenclature. Pedigree Standardization Task Force of the National Society of Genetic Counselors. AB - The construction of an accurate family pedigree is a fundamental component of a clinical genetic evaluation and of human genetic research. Previous surveys of genetic counselors and human genetic publications have demonstrated significant inconsistencies in the usage of common pedigree symbols representing situations such as pregnancy, termination of pregnancy, miscarriage, and adoption, as well as less common scenarios such as pregnancies conceived through assisted reproductive technologies. The Pedigree Standardization Task Force (PSTF) was organized through the Professional Issues Committee of the National Society of Genetic Counselors, to establish recommendations for universal standards in human pedigree nomenclature. Nomenclature was chosen based on current usage, consistency among symbols, computer compatibility, and the adaptability of symbols to reflect the rapid technical advances in human genetics. Preliminary recommendations were presented for review at three national meetings of human genetic professionals and sent to > 100 human genetic professionals for review. On the basis of this review process, the recommendations of the PSTF for standardized human pedigree nomenclature are presented here. By incorporating these recommendations into medical genetics professional training programs, board examinations, genetic publications, and pedigree software, the adoption of uniform pedigree nomenclature can begin. Usage of standardized pedigree nomenclature will reduce the chances for incorrect interpretation of patient and family medical and genetic information. It may also improve the quality of patient care provided by genetic professionals and facilitate communication between researchers involved with genetic family studies. PMID- 7887431 TI - Timing and genetic rapport between growth in skeletal maturity and height around puberty: similarities and differences between girls and boys. AB - We have analyzed longitudinal twin data by using a multivariate normal model to identify and quantify genetic effects over time on two main aspects of growth, height and skeletal maturity. The largest genetic contribution to the variance in both height and skeletal maturity coincided with the respective ages of peak growth velocity. The highest genetic covariance between these two traits coincided with the age of greatest acceleration of growth in height. These findings imply the existence of regulatory or structural genes that influence growth in both height and skeletal maturity. We also found sex differences in the rapport between velocities for height and skeletal maturity. These are consistent with a predominant role of estrogen in accelerating skeletal maturation in females, and the existence of additional mechanisms in males which may promote growth in height independently of the effects of gonadal sex steroids. PMID- 7887433 TI - Prenatal genetic counseling for hemoglobinopathy carriers: a comparison of primary providers of prenatal care and professional genetic counselors. AB - Health personnel trained in medical genetics are insufficient to meet the demand for genetic services. Methods must be found to enable primary care providers to offer commonly needed genetic services themselves. In our recently reported community-wide prenatal screening program for hemoglobinopathies, 36% of women detected to have a hemoglobinopathy did not come to a tertiary center for counseling and thus may have not benefited from testing. To determine whether the efficiency of the program could be increased if counseling were provided by the prenatal care provider (obstetrician or family practitioner), we developed a pilot training program on the basis of our experience in offering such services and enlisted 68% of regional prenatal care providers to participate. The proportion of patients detected to have a hemoglobinopathy who received counseling was similar in the primary and tertiary provider groups: 59% versus 50%, respectively, for sickle trait, and 69% versus 66%, respectively, for beta thalassemia trait. Knowledge after counseling was also similar for the primary and tertiary provider groups: 64% versus 66% (mean % correct), respectively, for sickle trait, and 79% versus 78%, respectively, for beta-thalassemia trait. However, the two provider groups significantly differed with regard to whether or not the patient had her partner tested. For sickle trait, it was 25% for the primary providers but 49% for the tertiary providers (P < .001). For beta thalassemia trait, it was 47% for the primary providers but 78% for the tertiary providers (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887432 TI - Delivery of molecular genetic services within a health care system: time analysis of the clinical workload. The Molecular Genetic Study Group. AB - The most recent discoveries in molecular genetics today are rapidly incorporated into clinical practice and have resulted in an unprecedented expansion of medical options. Despite this, the impact of molecular genetics on health care services has yet to be evaluated. In order to begin this assessment, clinical genetic workload was prospectively collected from cases where molecular genetic testing was considered. Participation involved all 16 urban and outreach genetic centers regionalized to service the entire population of 10 million within the Canadian province of Ontario. Molecular genetic testing has been clinically available for > 5 years, as part of a publicly supported genetic network in which there are no direct costs to residents. Cross-sectional data were collected on 1,101 clients from 544 families involving 1,742 clinical actions relating to diseases in which molecular (DNA) tests were considered. Median times per clinical genetic action were as follows: formal counseling (60 min), case review (15 min), phone call (10 min), letter (15 min), specimen arrangement (15 min), and interpretation of molecular test results (10 min). Times varied significantly with the inheritance pattern of the disease, topics involved, and location. For any given genetic case, multiple clinical actions resulted in substantial time spent by the genetic professional. Clerical and administrative times were not captured. Workload unit measurements similar to those currently employed in hospital laboratories may be helpful for predicting the clinical resources and personnel that will be required as the use of molecular genetics by other medical specialties increases. PMID- 7887434 TI - A powerful likelihood method for the analysis of linkage disequilibrium between trait loci and one or more polymorphic marker loci. AB - Historically, most methods for detecting linkage disequilibrium were designed for use with diallelic marker loci, for which the analysis is straightforward. With the advent of polymorphic markers with many alleles, the normal approach to their analysis has been either to extend the methodology for two-allele systems (leading to an increase in df and to a corresponding loss of power) or to select the allele believed to be associated and then collapse the other alleles, reducing, in a biased way, the locus to a diallelic system. I propose a likelihood-based approach to testing for linkage disequilibrium, an approach that becomes more conservative as the number of alleles increases, and as the number of markers considered jointly increases in a multipoint test for linkage disequilibrium, while maintaining high power. Properties of this method for detecting associations and fine mapping the location of disease traits are investigated. It is found to be, in general, more powerful than conventional methods, and it provides a tractable framework for the fine mapping of new disease loci. Application to the cystic fibrosis data of Kerem et al, is included to illustrate the method. PMID- 7887435 TI - Multipoint linkage analysis using sib pairs: an interval mapping approach for dichotomous outcomes. AB - I propose an interval mapping approach suitable for a dichotomous outcome, with emphasis on samples of affected sib pairs. The method computes a lod score for each of a set of locations in the interval between two flanking markers and takes as its estimate of trait-locus location the maximum lod score in the interval, provided it exceeds the prespecified critical value. Use of the method depends on prior knowledge of the genetic model for the disease only through available estimates of recurrence risk to relatives of affected individuals. The method gives an unbiased estimate of location, provided the recurrence risk are correctly specified and provided the marker identity-by-descent probabilities are jointly, rather than individually, estimated. I also discuss use of the method for traits determined by two loci and give an approximation that has good power for a wide range of two-locus models. PMID- 7887436 TI - An E-M algorithm and testing strategy for multiple-locus haplotypes. AB - This paper gives an expectation maximization (EM) algorithm to obtain allele frequencies, haplotype frequencies, and gametic disequilibrium coefficients for multiple-locus systems. It permits high polymorphism and null alleles at all loci. This approach effectively deals with the primary estimation problems associated with such systems; that is, there is not a one-to-one correspondence between phenotypic and genotypic categories, and sample sizes tend to be much smaller than the number of phenotypic categories. The EM method provides maximum likelihood estimates and therefore allows hypothesis tests using likelihood ratio statistics that have chi 2 distributions with large sample sizes. We also suggest a data resampling approach to estimate test statistic sampling distributions. The resampling approach is more computer intensive, but it is applicable to all sample sizes. A strategy to test hypotheses about aggregate groups of gametic disequilibrium coefficients is recommended. This strategy minimizes the number of necessary hypothesis tests while at the same time describing the structure of disequilibrium. These methods are applied to three unlinked dinucleotide repeat loci in Navajo Indians and to three linked HLA loci in Gila River (Pima) Indians. The likelihood functions of both data sets are shown to be maximized by the EM estimates, and the testing strategy provides a useful description of the structure of gametic disequilibrium. Following these applications, a number of simulation experiments are performed to test how well the likelihood-ratio statistic distributions are approximated by chi 2 distributions. In most circumstances the chi 2 grossly underestimated the probability of type I errors. However, at times they also overestimated the type 1 error probability. Accordingly, we recommended hypothesis tests that use the resampling method. PMID- 7887437 TI - A note on the application of the transmission disequilibrium test when a parent is missing. PMID- 7887438 TI - mtDNA D-loop 6-bp deletion found in the Chilean Aymara: not a unique marker for Chibcha-speaking Amerindians. PMID- 7887439 TI - Hantavirus pulmonary syndrome. Pathogenesis of an emerging infectious disease. AB - A recent outbreak of a severe pulmonary disease in the southwestern United States was etiologically linked to a previously unrecognized hantavirus. The virus has been isolated from its major reservoir, the deer mouse, Peromyscus maniculatus, and recently named Sin Nombre virus. Clinically, the disease has become known as the hantavirus pulmonary syndrome (HPS). Since May 1993, 44 fatal cases of HPS have been identified through clinicopathological review and immunohistochemical (IHC) testing of tissues from 273 patients who died of an unexplained noncardiogenic pulmonary edema. In 158 cases for which suitable specimens were available, serological testing and/or reverse transcription-polymerase chain reaction (RT-PCR) amplification of extracted RNA was also performed. IHC, serological, and PCR results were concordant for virtually all HPS and non-HPS patients when more than one assay was performed. The prodromal illness of HPS is similar to that of many other viral diseases. Consistent hematological features include thrombocytopenia, hemoconcentration, neutrophilic leukocytosis with a left shift, and reactive lymphocytes. Pulmonary histopathological features were similar in most of the fatal HPS cases (40/44) and consisted of an interstitial pneumonitis with a variable mononuclear cell infiltrate, edema, and focal hyaline membranes. In four cases, however, pulmonary features were significantly different and included diffuse alveolar damage and variable degrees of severe air space disorganization. IHC analysis showed widespread presence of hantaviral antigens in endothelial cells of the microvasculature, particularly in the lung. Hantaviral antigens were also observed within follicular dendritic cells, macrophages, and lymphocytes. Hantaviral inclusions were observed in endothelial cells of lungs by thinsection electron microscopy, and their identity was verified by immunogold labeling. Virus-like particles were seen in pulmonary endothelial cells and macrophages. HPS is a newly recognized, often fatal disease, with a spectrum of microscopic morphological changes, which may be an important cause of severe and fatal illness presenting as adult respiratory distress syndrome. PMID- 7887440 TI - Severe combined immunodeficiency mouse and human psoriatic skin chimeras. Validation of a new animal model. AB - Research into the cause and pathophysiological mechanisms underlying expression of psoriatric skin lesions has been hampered by lack of an appropriate animal model for this common and enigmatic cutaneous disease. These studies characterize normal skin, pre-psoriatic skin, and psoriatic plaque skin samples transplanted onto severe combined immunodeficiency mice. In this report we document that 1), normal, prepsoriatic, and psoriatic plaque keratome skin samples can be transplanted onto severe combined immunodeficiency mice reliably with high rates of graft survival (> 85%) and with reproducible changes consistently observed over prolonged periods of engraftment; 2), after transplantation, by clinical assessment and routine light microscopy, normal skin remained essentially normal whereas pre-psoriatic skin became thicker, and psoriatic plaque skin retained its characteristic plaque-type elevation and scale; 3), by using a panel of antibodies and immunohistochemical analysis, the overall phenotype of human cell types (including immunocytes) that persisted in the transplanted skin was remarkably similar to the immunophenotype of pretransplanted skin samples; 4), clearly recognized interface zones between human and murine skin within the epidermal and dermal compartments could be identified by routine microscopy and immunostaining, with focal areas of chimerism; and 5), elevated interleukin 8 cytokine levels were present in transplanted pre-psoriatic and psoriatic plaque skin samples. We conclude that there are many similarities between pre- and post transplanted human samples of normal and psoriatic skin that are grafted onto severe combined immunodeficiency mice. Thus, we propose that this new animal model is appropriate for additional mechanistic-type studies designed to reveal the underlying genetic/etiological abnormality, as well as better illuminate the pathophysiological basis, for this important skin disease. PMID- 7887441 TI - Inhibition of growth of normal and human papillomavirus-transformed keratinocytes in monolayer and organotypic cultures by interferon-gamma and tumor necrosis factor-alpha. AB - The growth response of normal and human papillomavirus (HPV)-transformed cervical keratinocytes to interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha was investigated in monolayer and organotypic raft cultures. The proliferation rates of monolayer cultures were assessed by [3H]TdR incorporation and fluorimetric DNA titration. The growth of keratinocytes in organotypic cultures was estimated by their ability to stratify on collagen rafts and by immunohistochemistry for Ki67 antigen expression. IFN-gamma reduced the DNA synthesis of normal and HPV transformed keratinocytes in monolayer cultures and exerted a marked growth inhibitory effect in organotypic raft cultures. In control raft cultures, normal keratinocytes produced an epithelial sheet of approximately 10 cells in thickness that closely resembled normal cervical epithelium and was characterized by sparse Ki67 antigen-positive cells whereas HPV-transformed keratinocytes produced up to 15 poorly differentiated epithelial layers that were reminiscent of high grade cervical lesions seen in vivo and exhibited a full thickness Ki67 antigen expression. When normal and HPV-transformed keratinocytes were maintained in the presence of IFN-gamma, the epithelial sheet was reduced to a few cells in thickness and the density of Ki67 antigen-positive cells was decreased. A more pronounced growth inhibitory effect in monolayer and organotypic cultures was observed when IFN-gamma was associated with tumor necrosis factor-alpha Tumor necrosis factor-alpha alone reduced the DNA synthesis of normal keratinocytes but was significantly less effective than IFN-gamma to inhibit the growth of HPV transformed keratinocytes. These results suggest that similar responses in vivo to regulatory molecules may play a role in the development of HPV-related lesions. PMID- 7887442 TI - Expression of p53 protein related to the presence of human papillomavirus infection in precancer lesions of the larynx. AB - The aim of this study was to gain some insight into the relationship of human papillomavirus (HPV) infection to p53 expression and to some pathological parameters in precancerous lesions of the larynx. Formalin-fixed paraffin embedded tissue sections containing human laryngeal precancerous lesions were screened for p53 protein by immunohistochemistry with the monoclonal antibody DO7 and for the presence of HPV infection by polymerase chain reaction with consensus primers directed against the E6 gene. The presence of p53 protein was detected in 31 of 57 specimens (54.4%) including 7 of 9 cases with mild dysplasia (78%), in 4 of 9 cases with moderate dysplasia (44%), and in 15 of 23 cases with severe dysplasia (65%). Of 16 samples with keratotic benign squamous metaplasia, 5 were also p53 positive (31%). Of 6 samples that were HPV positive, all were of type 16. Interestingly, 3 of the 6 HPV-positive samples were p53 negative. There was 1 HPV-positive case with strong p53 staining and 2 HPV-positive cases with minimal p53 staining. The 2 HPV-positive cases with minimal p53 staining had mild dysplasia. The HPV-positive case with strong p53 staining displayed severe dysplasia. Of 23 cases that were both HPV and p53 negative, 11 presented with keratosis and no dysplasia, 5 with moderate dysplasia, and 7 with severe dysplasia. Our data indicate that nuclear accumulation of p53 protein, presumably resulting from p53 gene mutation, may occur in HPV-infected epithelial tissues. On the other hand, there are many precancer lesions, some exhibiting moderate or severe dysplasia, that are both HPV negative and p53 unreactive, suggesting that alterations of genes other than the E6 oncogene and the p53 tumor suppressor gene play a role in early laryngeal carcinogenesis. PMID- 7887443 TI - MTS1/p16/CDKN2 lesions in primary glioblastoma multiforme. AB - The multiple tumor suppressor 1 (MTS1) gene encoding the p16 inhibitor of cyclin dependent kinase 4 is deleted or mutated in a wide variety of human tumor cell lines, but the importance of this gene as a tumor suppressor in vivo appears to be highly dependent on tumor type. Because MTS1/p16/CDKN2 and the homologous MTS2/p15 gene map to a region of chromosome 9p21, which is frequently deleted in malignant gliomas, we searched for lesions of these genes in primary biopsies of glioblastoma multiforme (GBM). Our analysis confirms a sizable frequency of homozygous deletion of MTS1/p16/CDKN2 (9/27 cases) and also reveals a low but detectable frequency of intragenic DNA lesions (one point mutation in exon 2 leading to premature termination) among GBMs that retain one or both copies of the gene. No mutations were found in exon 2 of MTS2/p15 (12 cases examined), and one GBM showed a DNA deletion breakpoint in the 30 kb between MTS1/p16/CDKN2 and MTS2/p15 resulting in deletion of MTS1/p16/CDKN2 with retention of MTS2/p15. In contrast to the high-grade tumors, none of 12 low-grade gliomas showed MTS1/p16/CDKN2 deletions. These data support a role for MTS1/p16/CDKN2 as a tumor suppressor gene in the in vivo evolution of GBMs. Given that two tumors with hemizygous MTS1/p16/CDKN2 deletions and loss of heterozygosity for chromosome 9p21 did not contain detectable intragenic mutations, there may be one or more additional relevant 9p21 tumor suppressor genes. PMID- 7887444 TI - A microdissection technique for archival DNA analysis of specific cell populations in lesions < 1 mm in size. AB - We have developed a microdissection technique that allows for procurement and analysis of specific, minute cell populations from routine, 5-mu, formalin-fixed, paraffin-embedded histological tissue sections. Lesions < 1 mm in size can be specifically examined. Cells of interest are procured under direct microscopic visualization followed by a single-step DNA extraction and subsequent polymerase chain reaction. Amplification of DNA from selected cell populations was demonstrated by detecting a loss of heterozygosity (LOH) at the von Hippel-Lindau disease (VHL) gene in an atypical renal lesion and a renal cell carcinoma in a kidney of a VHL patient. Moreover, previously unrecognized LOH on the short arm of chromosome 3 (3p25-26) was detected in microdissected colorectal carcinoma cells in a non-VHL patient with sporadic colon carcinoma. This technique should prove useful in DNA studies of small lesions and cell populations. Furthermore, microscopic premalignant, in situ, and invasive lesions can be selectively examined. PMID- 7887445 TI - Multiplex RT-PCR assay for the differential diagnosis of alveolar rhabdomyosarcoma and Ewing's sarcoma. AB - Cytogenetic analysis has defined specific translocations associated with two of the most common small round cell tumors of childhood, t(11;22) in Ewing's sarcoma and t(2;13) in alveolar rhabdomyosarcoma. We and others have previously demonstrated the diagnostic utility of a reverse transcriptase polymerase chain reaction (RT-PCR) assay for the detection of the t(11;22) encoded EWS/FLI-1 chimeric message in Ewing's sarcoma. More recently, we have cloned the t(2;13)(q35;q14) translocation and have shown that it results in the fusion of the PAX3 gene on chromosome 2 to FKHR, a novel member of the fork-head family of transcription factors on chromosome 13. To define the morphological spectrum of childhood sarcomas that express the t(2;13) encoded PAX3/FKHR chimeric message, we have performed RT-PCR analysis on samples from 44 primary pediatric sarcomas and 8 sarcoma cell lines. PAX3/FKHR chimeric messages were detected in 24 of 27 alveolar, 2 of 12 embryonal, and 0 of 1 pleomorphic rhabdomyosarcoma and in 1 of 2 ectomesenchymomas. In contrast, none of 8 Ewing's sarcomas or 2 undifferentiated sarcomas expressed this message. Chimeric transcripts were detected in all cases with cytogenetic evidence of the (2;13) translocation, and in each case the chimeric PAX3/FKHR message had the identical junction sequence, suggesting that genomic chromosome breaks were clustered in a single intron in both genes. By combining the PAX3/FKHR RT-PCR assay with primers for detection of the Ewing's sarcoma t(11;22) encoded EWS/FLI-1 chimeric transcript, we have developed a multiplex RT-PCR reaction that allows the rapid and accurate identification of either translocation in a biopsy sample. PMID- 7887446 TI - Up-regulation of T helper 2 and down-regulation of T helper 1 cytokines during murine retrovirus-induced immunodeficiency syndrome enhances susceptibility of a resistant mouse strain to Leishmania amazonensis. AB - Resistance to and recovery from leishmania infection is dependent on cell mediated immunity. C57BL/6 mice are resistant to Leishmania amazonensis (La) infection but susceptible to LP-BM5 murine leukemia virus (MuLV) infection. MuLV infection leads to a state of immunodeficiency characterized by severe compromise of cell-mediated immunity. When infected with La alone, C57BL/6 mice developed a small transient lesion that evolved to spontaneous healing or a lesion with extremely slow growth. Lesions were predominantly comprised of a lympho macrophagic infiltrate with few parasitized macrophages. When infected with La and, 4 weeks later, with MuLV (La-MuLV), the mice developed a large uncontrolled nonhealing lesion containing vacuolated and heavily parasitized macrophages. In contrast, mice infected with MuLV first and La 4 weeks later (MuLV-La) developed a small but persistent lesion, characterized histologically by a small number of heavily parasitized macrophages and few lymphocytes. Eight weeks after MuLV infection, both had similar immunological profiles with decreased lymphocyte proliferation, diminished production of interferon-gamma, and high production of interleukins 4 and 10. At the time of L. amazonensis infection, La-MuLV animals have a normal T cell function whereas in MuLV-La mice this function is already impaired; this may influence the recruitment of macrophages to the site of leishmania injection. PMID- 7887447 TI - Human melanocytes and melanoma cells constitutively express the Bcl-2 proto oncogene in situ and in cell culture. AB - The Bcl-2 proto-oncogene regulates cell survival by antagonizing events that lead to apoptotic cell death and has been reported to be expressed in situ in lymphoid tissues, glandular epithelium, neurons, and basal epidermal cells. When we performed immunostaining on cryostat sections of normal skin, anti-Bcl-2 reactivity was confined to scattered dendritic cells in the basal epidermal layer. Double-staining experiments showed that the Bcl-2+ cells were positive for vimentin but negative for cytokeratins, CD1a, and CD45 antigens, excluding keratinocytes and Langerhans cells as possible candidates for constitutive Bcl-2 expression. Bcl-2+ epidermal cells also reacted with the monoclonal anti melanocyte antibody NKI/beteb, and were absent from lesional skin in vitiligo, confirming that they represented epidermal melanocytes. Western blot analysis of cultured melanocytes and melanoma cell lines revealed a 26-kd protein specifically reacting with the anti-Bcl-2 monoclonal antibody. Immunostaining of pigmented lesions revealed strong expression of Bcl-2 by five of five nevocellular nevi and seven of seven melanomas. Our observations demonstrate that, within normal human epidermis, melanocytes are the only cells that express Bcl-2 constitutively and that Bcl-2 is expressed in benign and malignant pigmented tumors of the skin in situ. PMID- 7887448 TI - Expression of c-ErbB2 in human neuroblastoma tissues, adrenal medulla adjacent to tumor, and developing mouse neural crest cells. AB - We have examined the expression of c-ErbB2 in primary neuroblastoma tissues, mouse neural crest-derived tissues, and human adrenal gland adjacent to neuroblastoma tissue and of age-matched controls. c-ErbB2 expression was observed in approximately 60% of cases analyzed, and there were two staining patterns; one showed focal and cytoplasmic and the other showed diffuse and membrane staining patterns. The expression of c-ErbB2 in neuroblastoma tissues was confirmed by reverse transcription polymerase chain reaction and Western blot analysis. Diffuse and membrane staining of c-ErbB2 was well correlated with high urinary catecholamine secretion. In mouse tissues, cytoplasmic expression of c-ErbB2 was observed in immature peripheral neurons and adrenomedullary cells. In mature neurons, the immunoreactivity was confined to the plasma membrane. These results suggest that the expression of c-ErbB2 in neuroblastoma reflects the phenotype of developing peripheral neurons. Postnatal human and mouse adrenomedullary cells lacked c-ErbB2 immunoreactivity, although apparently normal adrenomedullary cells adjacent to neuroblastoma tissues showed strong cytoplasmic expression of c ErbB2. It is not known whether the phenotypic conversion of adjacent adrenal medullary cells had occurred before or after tumor progression at present. PMID- 7887449 TI - Catalase-negative peroxisomes: transient appearance in rat hepatocytes during liver regeneration after partial hepatectomy. AB - Using light microscopy enzyme cytochemistry to localize catalase activity in peroxisomes, a population of peroxisome-negative hepatocytes was detected in livers of rats during liver regeneration induced by two-thirds partial hepatectomy. However, examination by electron microscopy revealed that this population of hepatocytes contained peroxisomes with a delimiting membrane and a nucleoid, but no cytochemically demonstrable catalase activity within their matrix. Regenerating livers 6, 18, 24, 36, 48 and 72 hours, and 1 week after partial hepatectomy showed hepatocytes without catalase activity. However, their numbers varied, with the most numerous appearing at 24 hours after partial hepatectomy. Mitosis of catalase-negative hepatocytes were seen along with mitosis of hepatocytes containing the normal complement of catalase-positive peroxisomes. The catalase-negative hepatocytes did not show evidence of apoptosis or necrotic cell death. Lysosomal acid phosphatase activity and bile canalicular ATPase activity were present in hepatocytes with catalase-negative peroxisomes. Another population of hepatocytes with a small number of catalase-positive peroxisomes appeared and were more numerous at 36 hours after partial hepatectomy; ultrastructurally, these hepatocytes contained both catalase negative peroxisomes, which appeared to undergo dissolution, and catalase positive peroxisomes, which were smaller in size. After complete restoration of the liver, all hepatocytes displayed essentially uniform numbers of catalase positive peroxisomes. These studies indicated that during liver regeneration there is a transient loss of catalase in peroxisomes of some hepatocytes. These cells proliferate and with time acquire new catalase-positive peroxisomes. The observations are discussed in relation to peroxisome biogenesis, hepatocellular carcinogenesis, and oxidative stress during liver regeneration. PMID- 7887450 TI - Expression of receptors for advanced glycation end products in peripheral occlusive vascular disease. AB - The cellular interactions of advanced glycation end products (AGEs), which have been hypothesized to contribute to the development of vascular lesions, occur, at least in part, through their binding to a novel integral membrane protein, the receptor for AGEs (RAGE). Studies of human vascular segments show that endothelial RAGE expression at the antigen and mRNA level was variable and usually at low levels in samples from healthy individuals. In contrast, patients with a range of peripheral occlusive vascular diseases, with or without underlying diabetes, demonstrated prominent enhancement of endothelial RAGE expression. Smooth muscle cells and nerves in the vessel wall showed constitutively high levels of RAGE expression that were unchanged with aging (from 1 to 92 years) or by the presence of vascular disease. These data suggest that RAGE is likely to have ligands other than AGEs, and that multiple factors in addition to AGEs impact on its expression. Taken together, our findings suggest that RAGE may contribute to the pathogenesis of a range of vascular disorders. PMID- 7887451 TI - Adhesion systems in normal breast and in invasive breast carcinoma. AB - To analyze the role of various elements of the adhesion system in the organization of the normal mammary gland and in breast carcinoma, we have studied simultaneously the expression of integrins, E- and P-cadherins, and cytoplasmic constituents of adherens junctions. In the normal gland, E-cadherin and alpha catenin are present in luminal epithelial and myoepithelial cells, whereas integrins are more abundant in acinar epithelial and in myoepithelial cells. We demonstrate here that, in addition, myoepithelial cells express much more vinculin and alpha-actinin than luminal epithelial cells, whereas talin and focal adhesion kinase (pp125FAK) are restricted to the basal cell layer. In invasive carcinoma, E-cadherin is usually present although often in reduced amount; different integrin subunits are expressed either by a fraction or by all of the cells or are absent. However, the cytoplasmic components of adherens junctions, such as alpha-catenin, vinculin, alpha-actinin, talin, and pp125FAK, are expressed at low levels or cannot be detected in the carcinoma cells. Our data suggest that 1), in the normal mammary gland, the myoepithelial cells, being particularly rich in integrins and cytoplasmic components of the adherens junctions, play an important role in the maintenance of tissue integrity; 2), in invasive carcinoma, cell aggregates may be maintained due to varying levels of expression of E-cadherin and/or integrins; and 3), interaction of the transmembrane adhesion molecules with the cytoskeleton in carcinoma may be impaired as revealed by reduced levels of expression of alpha-catenin, vinculin, alpha-actinin, talin, and pp125FAK. Importantly, carcinoma cells, when exposed to stroma during invasion, do not acquire the adhesion apparatus characteristic of normal cells in contact with the extracellular matrix. PMID- 7887452 TI - Distribution of integrin cell adhesion molecules in endometrial cancer. AB - Integrins are ubiquitous cell adhesion molecules that are involved in maintaining normal tissue morphology and have been implicated in the behavior of certain malignancies. We examined the expression of nine integrin subunits in 38 endometrial adenocarcinomas using immunohistochemistry. The pattern of integrin expression in the cancers was compared with that seen in the endometrium of 20 normal cycling women and 7 postmenopausal women. Integrin expression was correlated with grade, stage, nodal status, depth of invasion, steroid receptor status, and histological pattern. In endometrial cancers there was an inverse relationship between the number of integrins expressed and histological grade (P = 0.011). Of the normally expressed, constitutive endometrial epithelial integrin subunits (alpha 2, alpha 3, alpha 6, and beta 4), the least frequently seen in the cancers was the alpha 3 subunit (44.7%) and the most frequently found was alpha 6 (81.6%). The alpha 5 beta 1 integrin, a fibronectin receptor normally found only on endometrial stromal cells, was seen in 17.8% of cases of these epithelial cancers. In addition, a significant association was found between the loss of the alpha 2 beta 1 integrin and the presence of lymph node metastases (P < 0.001). These data suggest that a decline in integrin expression occurs more frequently in poorly differentiated endometrial cancers and that the loss of specific integrins may be associated with metastatic nodal spread. PMID- 7887453 TI - AIDS-related Kaposi's sarcoma: evidence for direct stimulatory effect of glucocorticoid on cell proliferation. AB - Glucocorticoid therapy has been linked to increased risk of development of Kaposi's sarcoma (KS), which has become epidemic among HIV-infected individuals. However, no experimental evidence is available to explain the role of glucocorticoid in KS biopathology. We investigated the direct effect of dexamethasone (Dex) on the growth of cultured KS cells derived from acquired immune deficiency syndrome (AIDS) patients (AIDS-KS). Dex significantly stimulated the proliferation of AIDS-KS cells. Moreover, simultaneous exposure to Dex and oncostatin M, a KS major cytokine, produced a dramatic synergistic effect on proliferation of AIDS-KS cell. This suggests an interaction between glucocorticoid and growth factor intracellular pathways in KS cells. The expression of glucocorticoid receptor protein and mRNA in AIDS-KS cell cultures was examined by radioimmunoassay and in situ hybridization, respectively. Compared with other well studied cell lines, AIDS-KS cells contain an unusually high level of glucocorticoid receptor protein, which is further upregulated by glucocorticoid treatment. RU-486, a glucocorticoid receptor antagonist, completely abolished the stimulatory effect of Dex and reduced the synergistic effect of Dex and oncostatin M on proliferation of AIDS-KS. These findings demonstrate that glucocorticoid stimulates directly the proliferation of AIDS-KS cells via the modulation of glucocorticoid receptor expression. PMID- 7887454 TI - Discordant expression of immunoglobulin and its associated molecule mb-1/CD79a is frequently found in mediastinal large B cell lymphomas. AB - Mediastinal large B cell lymphomas are uncommon neoplasms that are thought to originate from thymic B cells. An unusual feature of these neoplasms is that they often lack surface immunoglobulin (Ig), a molecule ubiquitously expressed by most mature B cells. In the present study we have analyzed 12 cases of mediastinal large B cell lymphoma for the expression of the mb-1/CD79a polypeptide. This is a component, together with B29/CD79b, of a heterodimer that is associated with surface Ig on normal B cells. Our aim was to see whether loss of Ig in this type of lymphoma is associated with loss of the accompanying CD79a molecule. We have also evaluated 128 B cell lymphomas of other categories to see whether any of them show discordance between mb-1 and Ig expression and analyzed 30 T cell lymphomas as Ig-negative controls. We found that 5 of the 7 mediastinal large B cell lymphomas with interpretable staining results for both mb-1 and Ig, lack Ig but expressed CD79a (mb-1). This phenotype was very rare in other categories of B cell lymphoma, being found among 110 cases in only 5 cases that were all follicular lymphoma. The remaining 105 B cell lymphomas displayed mb-1+/Ig+ phenotype. All 30 T cell lymphomas were mb-1 negative. We conclude that discordant mb-1/Ig expression occurs commonly in mediastinal large B cell lymphomas. In addition, the finding that 11 of 12 of these neoplasms express a phenotype (CD10-, CD19+, CD20+, CD21-, CD22+, CD23-/+) that is very similar to that described for thymic medullary B cells reinforces the idea that most mediastinal large B cell lymphomas are of thymic B cell origin. The correlation between mb-1 and Ig staining patterns in B cell lymphomas of other categories reveals that in the majority (90%), expression of the antigen receptor complex parallels that of mature B cells. These data therefore confirm that the expression of the mb-1 protein provides independent strong evidence for the B lineage of lymphomas and may be used for their routine phenotypic characterization. PMID- 7887455 TI - Aging-associated changes in renal extracellular matrix. AB - The composition of renal extracellular matrices was examined in 6-, 12-, 18-, and 24-month-old rats by immunofluorescence microscopy. No change in composition of tubular basement membrane was detected. Increased immunostaining for laminin chains B1 and s-laminin and thrombospondin characterized the thickened glomerular basement membrane. Interstitial collagens I and III were not detected in globally sclerotic glomeruli. The major change noted in the aged rat kidney at 24 months was generalized expansion of the interstitium by thrombospondin and fibronectin. In areas of tubular atrophy there was new expression of extra domain A (EDA)+ fibronectin. Collagens I and III were detected focally in the interstitium adjacent to areas of tubular atrophy, but otherwise collagens I, III, and IV and laminin did not contribute to the interstitial fibrosis. Interstitial fibrosis was detectable at 18 months of age and preceded the development of sclerotic glomeruli, tubular atrophy, or accumulations of interstitial collagen. These changes in extracellular matrix composition distinguish the aging kidney from other sclerotic forms of renal disease. PMID- 7887457 TI - Do livers "stream"? PMID- 7887456 TI - Basic fibroblast growth factor regulates type I collagen and collagenase gene expression in human smooth muscle cells. AB - Basic fibroblast growth factor (bFGF) is a multifunctional peptide well known for angiogenic, neurotropic, and mesoderm-inducing effects. In the present study, we have investigated the effects of bFGF on collagen and collagenase gene expression in human iliac arterial smooth muscle cells. We report that bFGF inhibits type I collagen gene expression and collagen biosynthesis, with concomitant stimulation of collagenase gene expression. The smooth muscle cells incubated with human recombinant bFGF decreased the mRNA steady state levels of pro-alpha 1(I) type I collagen by as much as 72%. [3H]Hydroxyproline synthesis was also suppressed by 59% compared with untreated control cultures. Indirect immunofluorescence confirmed corresponding changes at the protein level. In contrast to the down regulation of type I collagen gene expression, collagenase gene expression was found to be up-regulated severalfold by bFGF. The data suggest that bFGF is capable of regulating collagen and collagenase gene expression divergently in human smooth muscle cells and that the effects appear to be mediated at a pretranslational level. PMID- 7887458 TI - Diffuse senile plaques: amorphous or fibrous? PMID- 7887459 TI - Cleavage of type I procollagen by C- and N-proteinases is more rapid if the substrate is aggregated with dextran sulfate or polyethylene glycol. AB - The enzymes procollagen C- and N-proteinases specifically cleave carboxyl- and amino-terminal propeptides of procollagens. After cleavage of the propeptides, the resulting collagens self-assemble into fibrils. In most previous experiments with the enzymes, the substrate was monomeric type I procollagen. Here we have prepared aggregates of type I procollagen from chick embryo tendons by using 1 to 100 micrograms/ml of 500-kDa dextran sulfate or 3 to 5% (w/v) polyethylene glycol (M(r) 3350). Aggregation of the substrate with dextran sulfate increased its rate of cleavage by purified or crude C-proteinase from chick embryo tendons 10- to 15 fold. Aggregation of the substrate with 25 to 100 microgram/ml of dextran sulfate increased the rate of cleavage by purified N-proteinase about 4-fold. The rate of cleavage by crude N-proteinase was enhanced only about 2-fold, apparently because of partial precipitation of the enzyme by dextran sulfate. Using polyethylene glycol to aggregate the substrate increased the rate of cleavage by procollagen C proteinases 5- to 20-fold. Aggregation with polyethylene glycol also increased the rate of cleavage by purified procollagen N-proteinases 2- to 5-fold. With crude N-proteinase, the rate of cleavage was increased only 1.5-fold. The results suggest that the rate of cleavage of the substrate by both enzymes is increased by the aggregation of the substrate itself by dextran sulfate or polyethylene glycol. The increased rates of cleavage seen after aggregation of substrate can be used to develop more sensitive assays for the enzymic activities. PMID- 7887460 TI - An electrophoretic method to detect cold-induced dissociation of proteins in crude extracts of higher plants. AB - The phenomenon of cold denaturation has been firmly established recently in several proteins. Some multimeric enzymes from plant origins are believed to dissociate under some circumstances in the cold. To determine the presence and number of soluble, non-membrane-bound protein that undergoes cold-induced dissociation in plants, we have devised a special two-dimensional polyacrylamide gel electrophoretic method using two native gradient gels. Examination of the gel run at 0 degrees C in the second dimension showed the presence of four cold dissociated proteins running below the diagonal and staining intensely with silver, in the extract of maize leaves. The electrophoretic method described here is expected to be a convenient way to detect cold-induced dissociation of soluble proteins in crude extracts of various tissues. It is also possible to estimate roughly the molecular weights of both the cold-dissociated subunit and the native protein from which it is derived. PMID- 7887461 TI - Sequence analysis of lantibiotics: chemical derivatization procedures allow a fast access to complete Edman degradation. AB - Lantibiotics are antibiotic peptides produced via ribosomal synthesis of precursor proteins by gram-positive bacteria. They contain various unusual post translational modifications, which include the formation of sulfide rings by lanthionine or beta-methyllanthionine, and 2,3-didehydroamino acids. The N terminus may be blocked by a 2-oxobutyryl group and the C-terminus may be inaccessible in some of the lantibiotics. Due to these modifications the analysis of such peptides is very tedious. Chemical modifications using an ethanethiol containing reaction mixture and/or trifluoroperacetic acid treatment were used to solve these analytical problems. Investigating the tetracyclic 22-peptide gallidermin and the N-terminally blocked tricyclic 34-peptide Pep5 as examples, a novel access to the primary structure of lantibiotics is demonstrated. PMID- 7887462 TI - High-performance liquid chromatographic analysis of synthetic peptides using derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. AB - A series of synthetic prothrombin leader sequences (ANKGFLEEX), each having a different C-terminal amino acid, was derivatized with the novel fluorescent derivatizing agent 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate and analyzed by HPLC. Essentially quantitative yields of derivatized peptides could be routinely obtained with a fast, simple derivatizing procedure. The response was linear over a concentration range of 0.176 to 88.0 nM. Peptides labeled with this highly sensitive derivatizing agent exhibited a mass detection limit in the femtomole range and a concentration detection limit in the picomolar range. Amino acid content of hydrolyzed peptides was carried out using the same reagent in order to evaluate the amino acid composition and to detect any deletion sequences. PMID- 7887463 TI - Capillary electrophoretic analysis of serine hydroxymethyltransferase in Escherichia coli fermentation broth. AB - Serine hydroxymethyltransferase (SHMT) expressed in Escherichia coli was analyzed in fermentation broth through the use of capillary electrophoresis (CE), a method which provided advantages over the traditional techniques of slab gel electrophoresis and chromatography. In addition, via CE the difficult resolution and quantitation of SHMT holoenzyme and apoenzyme were achieved. Using this method, a pyridoxal-5'-phosphate (PLP) cofactor/SHMT dimer molar ratio of 0.65 was estimated to be present in holoenzyme in the absence of excess PLP. This determination correlated well with results obtained by other techniques, including electrospray ionization mass spectrometry (ESI-MS). CE and ESI-MS analyses both provided evidence for significant differences between the folded conformations of SHMT holoenzyme and apoenzyme. PMID- 7887464 TI - Assay of ornithine aminotransferase with ninhydrin. AB - We developed an assay system for ornithine aminotransferase (EC 2.6.1.13) using ninhydrin. Pyrroline 5-carboxylate, a product of enzymatic transamination, reacts with ninhydrin under hot acidic conditions to form a reddish pigment soluble in ethanol. The millimolar extinction coefficient of reaction product dissolved in ethanol was 16.5 at 510 nm. Acidification with perchloric acid effectively abolished the interfering color development by L-ornithine and L-glutamate. The paired activity measurement in mouse tissues by ninhydrin and o-aminobenzaldehyde methods showed a good correlation (gamma = 0.985). In our ninhydrin method, stable ninhydrin replaced unstable o-aminobenzaldehyde, and sensitivity was much higher than that with the conventional o-aminobenzaldehyde method. PMID- 7887466 TI - An enzyme-linked immunosorbent assay method to measure human apolipoprotein E levels using commercially available reagents: effect of apolipoprotein E polymorphism on serum apolipoprotein E concentration. AB - A sensitive and specific enzyme-linked immunosorbent assay (ELISA) for human apolipoprotein E (apo E) quantification using commercially available reagents is described. The assay is a noncompetitive, sandwich ELISA in which the wells were coated with a monoclonal EO1 antibody anti-human apo E and detected with a polyclonal antibody-peroxidase conjugate anti-apo E. The mean apo E concentration in 168 middle-aged subjects randomly selected from general population was 51.7 +/ 12.4 mg/liter. Apo E levels were highly correlated with apo E phenotypes. Apo E polymorphism, which shows a modulating effect in the catabolism of apo E containing lipoproteins, may explain a large fraction, 18.5%, of the variability of serum apo E levels in middle-aged population. Isoforms apo E2 and apo E4 have an opposite effect on the regulation of serum apo E concentrations. Individuals that express apo E2 isoform present higher apo E levels (65.5 mg/liter for apo E2/E3), whereas the average of individuals with apo E4 is lower (42.8 mg/liter for apo E4/E3) than general population. PMID- 7887465 TI - Specific labeling of diaminopimelate: a radioassay for the determination of the peptidoglycan cross-linking index. AB - A radioassay for the determination of the peptidoglycan cross-linking index (CLI) was devised. It is based on specific radioactive labeling of diaminopimelic acid (DAP) by diverting [14C]aspartate into the DAP pathway, while inhibiting incorporation of label into other cell wall components. Purified [14C]DAP-labeled cell walls were treated with fluorodinitrobenzene, hydrolyzed, and chromatographed by TLC. The radioactivity in well-separated mono dinitrophenyl diaminopimelate (DNP-DAP) and DAP spots was counted and the CLI was determined from the ratio of DAP to the total of mono DNP-DAP and DAP counts. The method, suitable for bacteria such as Bacillus subtilis unable to incorporate exogenous DAP, can be applied to other systems. A CLI of 50.8 +/- 1.3% and 55.5 +/- 0.9% was obtained for B. subtilis 168 cells growing exponentially in rich and minimal medium, respectively. Comparison of these to results previously obtained on B. subtilis suggested the existence of a hitherto unreported peptidoglycan endopeptidase activity. PMID- 7887467 TI - Oligosaccharides from human milk as revealed by matrix-assisted laser desorption/ionization mass spectrometry. AB - In this study neutral and acidic oligosaccharide fractions prepared from human milk have been investigated using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The fraction of neutral oligosaccharides was separated by gel permeation chromatography (GPC) and the resulting subfractions were analyzed by MALDI-MS using the positive ion mode. Several low-molecular weight glycans (degree of polymerization up to 13) were observed whose structures have already been elucidated. In addition, a variety of so far unknown large sized carbohydrates was detected whose molecular weights range from M(r) 2242 to 8000. The large-sized glycans which possess a low abundance appear to be composed of both lactosamine and fucose residues attached to the lactose unit at the reducing end of the sugar chains with a highly variable stochiometry. Following subfractionation by GPC, acidic (i.e., containing sialic acid) glycans were analyzed by MALDI-MS using both positive and negative ion mode. Because of the inferior stability of acidic glycans, various matrices were applied and compared with respect to signal intensity, resolution, and analyte stability. PMID- 7887468 TI - A nonradioactive assay for microsomal cysteine-S-conjugate N-acetyltransferase activity by high-pressure liquid chromatography. AB - Microsomal cysteine-S-conjugate N-acetyltransferase, an enzyme specific for S substituted cysteines, plays an important role in the detoxicative metabolism of xenobiotics by catalyzing the N-acetylation of cysteine-S-conjugates. Cysteine-S conjugate N-acetyl-transferase activity is generally assayed by measuring the amount of N-[14C]acetyl-S-benzyl-L-cysteine generated from the model compound S benzyl-L-cysteine and [14C]acetyl-CoA and subsequent extraction of the product. Although sensitive, this method is costly and time consuming. For safety and environmental reasons we developed a nonradioactive assay for cysteine-S conjugate N-acetyltransferase activity. Our method depends upon the acetylation of the uv-sensitive model compound 4-nitro-S-benzyl-L-cysteine. The test mixture is separated by HPLC, guaranteeing that no by-products interfere with the determination of product formation. Radioactive and nonradioactive methods were compared using different porcine kidney samples. With the nonradioactive test we determined values of Km and Vmax of both 4-nitro-S-benzyl-L-cysteine and acetyl CoA. In summary, this new nonradioactive assay is sensitive, less costly, safer, less time-consuming, and less laborious than radioactive assays for cysteine-S conjugate N-acetyltransferase. PMID- 7887469 TI - A simple and quantitative purification of glycosphingolipids and phospholipids by thin-layer chromatography blotting. AB - A new and simple method for purifying glycosphingolipids and phospholipids by using "TLC blotting" was established. Glycosphingolipids separated by two dimensional thin-layer chromatography (TLC) were made visible with primuline reagent, and then bands were marked with a drawing colored pencil. The glycosphingolipids that separated on the HPTLC plate were transferred by TLC blotting to a polyvinylidene difluoride membrane together with the color marks. The marked areas were excised after which their glycosphingolipids were extracted and monitored by TLC. By this method, 20 glycosphingolipids showing homogeneous bands on a HPTLC plate were isolated from the neutral glycosphingolipid fraction of human meconium. Moreover, 10 kinds of acidic glycosphingolipids were purified as homogeneous bands from the bovine acidic glycosphingolipid fraction. The yields of glycosphingolipids (13 different ones) ranged from 68 to 92%, the mean value being 82.3%. The glycosphingolipids were confirmed to be purified as intact forms by mass spectrometric analysis and chromatographic mobilities on a HPTLC plate. The same procedure could also be used to purify phospholipids. PMID- 7887470 TI - An improved method for absolute quantification of mRNA using multiplex polymerase chain reaction: determination of renin and angiotensinogen mRNA levels in various tissues. AB - We have developed a multiplex, competitive, reverse-transcriptase polymerase chain reaction (RT-PCR) method which measures absolute levels of renin, angiotensinogen, and the housekeeping transcript elongation factor-1 alpha (EF-1 alpha) mRNA. Sample RNA was simultaneously titrated with serial dilutions of renin, angiotensinogen, and EF-1 alpha competitor RNAs which flanked the endogenous concentrations of target transcripts. The samples were coreverse transcribed in the presence of random primers and resulting first-strand cDNA was coamplified for 10-15 cycles with [32P]-dCTP and primers for renin angiotensinogen, after which EF-1 alpha primers were added. Amplified DNA was separated by electrophoresis on polyacrylamide gel and radioactivity in the bands was quantified by direct radioanalytical scanning. Three conditions were necessary to obtain absolute quantification of renin and angiotensinogen mRNA levels: (a) exogenous competitor RNA was used to control for tube-to-tube variability in the efficiencies of reverse transcription and amplification; (b) Sample RNA was titrated with flanking concentrations of competitor RNA to correct for intraassay differences in the efficiency of amplification due to concentration differences between competitor and target templates; and (c) a housekeeping transcript EF-1 alpha was used to control for tube-to-tube differences in RNA loading and/or degradation. We show that the multiplex RT-PCR method is precise and accurate over approximately three logs of transcript concentration and sensitive to less than 5 and 0.5 fg for renin and angiotensinogen mRNA, respectively. This method will be useful for absolute quantification of target mRNAs, especially when the amount of sample RNA is limited or unknown and/or the gene expression is low. PMID- 7887471 TI - Monitoring mRNA expression by polymerase chain reaction: the "primer-dropping" method. AB - We have developed a method to monitor mRNA expression that is based upon the reverse transcriptase-polymerase chain reaction (RT-PCR) and includes multiple sets of primer pairs in coamplification reactions. To observe relative changes in mRNA steady-state levels, each target in a multiplex reaction was amplified to within a predetermined range by using PCR cycle numbers specific for each target. Optimal PCR cycle numbers for target templates were determined by preliminary titration experiments performed using the "primer-dropping" method. By employing this method, the overall amplification reaction was limited, permitting the PCR products to remain within the exponential range of the amplification curve and yet be detectable on ethidium bromide-stained gels. We demonstrated the utility of this method by monitoring the expression kinetics of cyclins A, B1, D1, and E, and of the immediate-early genes c-fos, c-myc, and beta-actin. Glyceraldehyde-3 phosphate dehydrogenase (GAPDH) was included in the multiplex reactions as an endogenous internal standard to control for variations in product abundances due to differences in individual RT and PCR reaction efficiencies. Changes in gene expression of less than twofold to greater than 75-fold were readily distinguished. PMID- 7887472 TI - Direct measurement of the binding of RAS to neurofibromin using a scintillation proximity assay. AB - Protein-protein interactions are of major importance in many cellular processes. When no enzymic activity is involved, assays for direct binding are required. One such example is the relatively weak interaction between oncogenic Ras and the GTPase-activating protein neurofibromin (NF1). The complex between the catalytic domain of NF1 and the GTP-form of oncogenic Ras protein dissociates rapidly; hence, equilibrium binding must be quantitated. Scintillation proximity assay (SPA) technology, a radioisotopic technique that requires no separation step, was used to characterize this interaction. Leu-61 Ras complexed with [3H]GTP was generated by nucleotide exchange in the presence of a GTP-regenerating system. A SPA signal was obtained when radiolabeled Ras was mixed with NF1 fused with glutathione S-transferase (GST), anti-GST, and protein A-coated SPA beads. This signal was abolished when any of the components were omitted and also by the addition of NaCl, which potently reduces the affinity of interaction between Ras and NF1. The neutralizing anti-Ras monoclonal antibody Y13-259 and the detergent n-dodecyl maltoside, a specific inhibitor of NF1 catalytic activity, both abolished the SPA signal from the NF1/Ras assay but neither affected a control SPA signal in which a [3H]GTP.GST-Ras fusion protein was bound to protein A coated SPA beads. This technology could be readily extended to the measurement of other protein-protein interactions and could form the basis for high-throughput screens for the discovery of novel therapeutic agents. PMID- 7887473 TI - A specific fluorometric assay for hexosamines in glycosaminoglycans, based on deaminative cleavage with nitrous acid. AB - Glycosaminoglycan (GAG) hexosamines were measured after deacetylation (2 h acid hydrolysis), deaminative cleavage by nitrous acid, and coupling of the 2,5 anhydro sugars thus produced with 3,5-diaminobenzoic acid (DABA) to give a fluorescent product. Analyses were performed after the addition of an aliquot of potassium acetate solution to the acid hydrolysates, to adjust the pH. Results on a series of GAGs were compared with an Elson-Morgan (E-M) procedure. Our method is faster, more convenient, 10-20 times more sensitive, and always gave higher figures for hexosamine content. In particular it avoids long, destructive hydrolysis in concentrated strong acid and the complications of the Moggridge Neuberger effect. Results agreed with calculations and titrimetric data. Using internal standards, our method is tolerant of cetylpyridinium chloride, peptides, and salts. A simple fluorometer easily handled less than 1 microgram GAG per sample in 1.0 ml volume. Results are available in 4-5 h. The method is suitable for automation. A strongly polycationic environment, as in chitosan, markedly slowed nitrous acid deamination, possibly because of Donnan-type exclusion from the domain of the polycation of the cationic nitrosonium species. Whereas all other alpha- and beta-hexosaminides gave yield-hydrolysis time profiles that peaked in approximately 1 h in the DABA method, the E-M profiles, particularly for 2-sulfamato-alpha-hexosaminides, took longer and/or achieved lower optimal yields. All the usually encountered forms of the 2-amino-2-deoxy group (free, acetylated, sulfamato) are readily assayed using the same reagents, with appropriate prefluorometric stages. PMID- 7887474 TI - Determination of plasma adenosine by high-performance liquid chromatography with column switching and fluorometric detection. AB - A new method for the rapid determination of plasma adenosine concentrations was developed by using high-performance liquid chromatography with a column switching technique and fluorometric detection. Several "stop solutions" were used to prevent the enzymatic degradation and cellular uptake and release of adenosine in blood samples. Red blood cells and certain denatured proteins were separated by centrifugation. Subsequently, the supernatant was transferred directly into autosample vials and adenosine was reacted with chloroacetaldehyde to form a strong fluorescent, 1-N6-ethenoadenosine. The adenosine derivative was injected directly and separated on a shielded hydrophobic phase column coupled with a C18 reverse-phase column using a column switching valve. Macromolecules and other interfering substances were excluded by the shielded hydrophobic phase column and bypassed to waste. Then, the adenosine derivative and other retained compounds were switched onto the reverse-phase column for further separation and subsequently to the fluorescence detector. The system reduces the analysis time and contamination of the column and hence allows a shorter cleanup time and a longer column lifetime. Adenosine as low as 30 fmol (signal-to-noise ratio, S/N = 3) can be detected by this method. The percentage of recovery of adenosine in plasma treated with adenosine deaminase was above 90%. This method is very rapid (without tedious sample preparation) and sensitive for determining adenosine in canine blood and should prove to be useful in analyzing the effects of ischemia and reperfusion on arterial and coronary venous adenosine concentrations in blood or perfusate samples released from the ischemic or hypoxic myocardium. PMID- 7887475 TI - Separation and characterization of diastereoisomers of antisense oligodeoxyribonucleoside phosphorothioates. AB - Diastereoisomers of oligodeoxyribonucleoside phosphorothioates (OPT) up to a tetramer were effectively separated with reversed-phase high-performance liquid chromatography (reversed-phase HPLC) under optimized conditions. The diastereoisomers of OPT resulted in different retention times on the reversed phase HPLC. From the results, we found that there were certain rules in the elution order of the diastereoisomers. The configurational sequence of the diastereoisomers was determined by digestion with nuclease P1, snake venom phosphodiesterase, and alkaline phosphatase. The diastereoisomers were studied by CD spectroscopy with respect to their conformation in aqueous media. We found that a large variation in the conformation of diastereoisomers exists. Results suggest that much attention should be paid to the diastereoisomerism in antisense molecules having chiral internucleotide linkages such as OPT. PMID- 7887476 TI - Sphingosine kinase from Swiss 3T3 fibroblasts: a convenient assay for the measurement of intracellular levels of free sphingoid bases. AB - Sphingoid bases are important for diverse cellular processes. This paper describes the development of a simple and rapid enzymatic method to quantify mass levels of free long-chain sphingoid bases in cellular lipid extracts. The assay is based on the ability of sphingosine kinase from Swiss 3T3 fibroblasts to phosphorylate sphingoid bases, predominantly sphingosine. To quantitatively determine cellular levels of sphingosine or other long-chain sphingoid bases, it was necessary to solubilize cellular lipids by sonication and to generate standard curves in the presence of lipid extracts containing at least 50 nmol of phospholipids. The assay conditions were optimized to allow quantification of sphingosine over a broad range from 25 to 1,000 pmol. Using this method we were able to obtain reproducible measurements of free sphingoid bases in various cell types and to detect increases in intracellular sphingoid base levels after treatment with exogenous sphingosine or stimulation with fetal bovine serum. PMID- 7887477 TI - A stable water-soluble tetramethylbenzidine-2-hydroxypropyl-beta-cyclodextrin inclusion complex and its applications in enzyme assays. AB - 3,3',5,5'-Tetramethylbenzidine (TMB), a hydrophobic and noncarcinogenic chromogen with a high absorption coefficient widely used in solid-phase assays involving labeled horseradish peroxidase was rendered soluble (up to 40 mM) and more stable for at least 2 months at 22-24 degrees C by forming a water-soluble inclusion complex with 2-hydroxypropyl-beta-cyclodextrin (hp-beta-CyD). Cyclic voltammetry and absorbency measurement were employed to characterize the TMB-hp-beta-CyD complex. Well-defined cyclic voltammograms of TMB exhibited two oxidation waves which merged into a single wave with increasing hp-beta-CyD concentrations. Cyclic voltammetry was then used to examine the effect of complexation with hp beta-CyD on the oxidation potential of TMB and provided evidence of a 1:1 complex between TMB and the cyclodextrin molecule with a formation constant of 1.6 M-1. Enzyme assays for D-glucose, lactate, and glutamate were performed by coupling the TMB-hp-beta-CyD/horseradish peroxidase system to the respective oxidase enzymes with the formation of either a blue (absorption coefficient of 35,800 M-1 cm-1 at 650 nm) or a yellow color (absorption coefficient of 67,300 M-1 cm-1 at 450 nm) as an indication of the metabolite concentration. These assays possessed a sensitivity limit below 10 microM and the results obtained were in excellent agreement with standard enzymatic assays when tested in various food and clinical samples. PMID- 7887478 TI - Protein determination in permeabilized yeast cells using the Coomassie brilliant blue dye binding assay. PMID- 7887479 TI - Luminol chemiluminescent assay of cytochrome b5. PMID- 7887480 TI - An assay of tritiated thymidine incorporation into DNA by cells cultured under anchorage-independent conditions. PMID- 7887481 TI - Anatomic observations of the coronary sinus in the dog (Canis familiaris). AB - The coronary sinus was investigated in 34 normal adult dogs, in order to verify its formation, tributaries, length and the valves, as well as the relationship of the venous walls to the epicardium and to the myocardium. The valve of the coronary sinus was observed in only 4 cases (1.7%). In 30 cases (98.3%) the ostium of the coronary sinus was lacking a valve. The valve of Vieussens double, was found at the level of the transition between the great cardiac vein and the coronary sinus, as well as others parietal venous valves. A comparison with the human pattern was made, particularly regarding the action of the valve of the coronary sinus and the formation of the sinus. PMID- 7887482 TI - [Histochemical and morphometric characteristics of some extraocular muscles of the dog]. AB - This investigation was carried out on retractor bulbi, lateral and medial rectus muscles of six adult dogs. Tissues were collected from near the center of individual muscle bellies. These were stained for m-ATPase at varying pHs during preincubation, NADH-TR, Alpha-GPDH, Modified Mason trichrome and Hematoxyline and Eosin. Muscle fibers were classified as type I and type II, based on their reaction for m-ATPase. The retractor bulbi muscle was composed entirely of type II, oxidative, muscle fibers, with no glycolytic fibers. The rectus muscles presented a stratified composition, with superficial muscle fiber bundles containing a mixture of type II fibers oxidative and glycolytic, and central bundles of type I, mixed with type II. It was observed that there was less interstitial tissue in the center of the muscle bellies. Large diameter nerve fibers were also observed in the central layers. PMID- 7887483 TI - The thymus of the guinea fowl from the eighteenth day of incubation until maturity. AB - The thymus gland of the guinea fowl appeared as a series of pink, irregular shaped lobes along the jugular veins. These lobes were 13 in number with seven on the right and six on the left side. The third and sixth lobes on the right side were the largest. The largest lobe measured about 20.0 x 5.0 mm while the smallest measured about 5.0 x 4.0 mm. Histologically, it was encircled by a thin layer of poorly stained connective tissue from which strands penetrated the thymic tissue giving incomplete lobules peripherally as early as day 18 of incubation. Lymphocytes and reticular epithelial cells were the two types of cells occurring at this time. Reticular epithelial cells were observed to be vacuolated especially towards the centre of the gland. Macrophages were observed in the thymus on day 20 of incubation for the first time. The blood vessels had accompanied the interlobular septa into the thymus. By day 21 of incubation, blood vessels had actually penetrated the thymic tissue but most of these vessels were of the capillary size. The cortex also became quite distinct from the medulla. At day 22, vacuolation ceased to appear in the cells at the cortical zone. Macrophages were still less than 10 in the slide. At day 23, most blood vessels were within the medulla and they displayed compressed lumina. Mitotic figures became a common site amongst the large lymphocytes and reticular epithelial cells. By day one post-hatch, lobulation of the thymus was still poor and macrophages became difficult to identify. The small and medium lymphocytes had outnumbered the large lymphocytes throughout the thymic tissue except at the most peripheral zone of the cortex. Fine vacuoles had reappeared within the cytoplasm of the reticular epithelial cells in the cortex. By day five, the distribution of blood vessels was almost uniform between the cortex and medulla. At three weeks post-hatch, plasma cells and red blood cells were seen in the stroma of the gland for the first time and most of the red blood cells occurred in the medulla. PMID- 7887484 TI - Enzyme-histochemical profiles of fiber types in mature canine appendicular muscles. AB - The histochemical characteristics of skeletal muscle were assessed using a range of samples from 7 appendicular muscles taken from adult mixed-breed dogs (1.5 to 3 years of age). Two slow-twitch fiber subtypes (IA and IB) and three II subtypes (IIA, IIB and IIC) were identified according to myofibrillar myosin adenosine triphosphatase reaction after acid and alkaline preincubation. Type IIB fibers were not found in all muscles, and were only biologically significant in m. semitendinosus. The metabolic potential of these fibers is fairly similar to that of IIA fibers, but significantly different to that of IIB fibers in other mammals, suggesting that they may be designed to play a different functional role during locomotion. All canine muscle fibers have moderate to high oxidative capacity, which may be related to the extraordinary athletic capability of the species. PMID- 7887485 TI - Some aspects of macroscopic studies of the placentation in the camel (Camelus dromedarius). AB - The paper presents some salient aspects of a study on the placentation of camel at gross, light and electron microscopic levels. The study involved factors analysis on five pregnant uteri from camel slaughter house in Yazd, Iran. The experimental observations confirmed that unlike other animals, in camel, the fetus only developed in the left horn of the uterus. Based on the distribution type of the chorionic villi, in camel, similar to horse, the placenta was found to be in diffused form. At light microscopic level, the results revealed six layers between the fetal and maternal blood. From this it inferred that camel's placenta was also of epitheliochorial form. The detailed examination further showed that similar to cow and sheep umbilical cord in camel was also limited to the amniotic sac but it contained two arteries, two veins and one urachus. Little amount of elastic fibers were also observed in the histological and electron microscopical sections. At the electron microscopic level, both binucleated and mononucleated cells in trophoblastic layer were confirmed. PMID- 7887486 TI - Ultrastructure of the hinny (Equus asinus x Equus caballus) seminiferous epithelium. AB - The gonads and the germinative cells of 3 male hinnies were studied with light and transmission electron microscopy with the aim to observe the development of germ cells and verify the morphological modifications due to the hybridization. The hinny seminiferous epithelium presented Sertoli cells and spermatogonia with normal features and anomalous spermatocytes I. The other cells from the spermatogenic sequence were not seen. Most of the alterations began to occur in the cytes I, which presented nuclear vacuolization and deposits of amorphous material between the carioteca and the nuclear lamina, forming vesicles, or exaggerated chromatin condensation, resulting in pyknosis. In the cytoplasm vacuolization was also observed, besides organelle destruction. The arrest of meiosis due to lock of chromosome homologies leads to germinative cell degeneration and, therefore, the spermatogenesis arrest. This fact causes a profound alteration in the seminiferous epithelium morphology in comparison with the parental species. PMID- 7887487 TI - Distribution of different fibre types of M. extensor carpi radialis longus of the rat. AB - As revealed by the NADH-diaphorase and myosine ATPase, the M. extensor carpi radialis longus of the rat possesses at least 3 main kinds of fibres, with different distribution on the superficial and deep portions of the muscle. The superficial portion revealed that 67.68% are FG (fast-twitch-glycolytic) fibres, 14.72% are FOG (fast-twitch-oxidative) fibres and 17.60% are SO (slow-twitch glycolytic) fibres. Already the deep portion revealed that 71.29% are SO (slow twitch-glycolytic) fibres, 17.46% are FOG (fast-twitch-oxidative-glycolytic) fibres and 11.25% are FG (fast-twitch-glycolytic) fibres. The miosine ATPase reaction was used to demonstrate contracting characteristics. These findings suggest that the movements of fast contraction of the M. extensor carpi radialis longus are predominant. PMID- 7887488 TI - Fine structure of the pecten oculi in the American crow (Corvus brachyrhynchos). AB - The pecten oculi of the American crow (Corvus brachyrhynchos) has been examined by both light and electron microscopy. In this species the pecten is very large and of the pleated type. It consists of 22-25 accordion folds that are joined apically by a bridge of tissue which holds the pecten in a fan-like shape widest at its base. Within each fold are numerous capillaries, larger supply and drainage vessels and many melanocytes. The capillaries are extremely specialized for transport functions and display extensive microfolds on both their luminal and abluminal borders. Except for the nuclear region which contains most of the organelles, the endothelial cell bodies are extremely thin. These capillaries are surrounded by thick fibrillar basal laminae which are conjectured to be structurally important. Pericytes are a common feature of these capillaries. The numerous pleomorphic melanocytes interspersed between the capillaries are also felt to be important in structural support of the pecten. The pecten is considered to be comparable to the falciform process of some teleosts, the conus papillaris of reptiles, the supraretinal vessels of amphibians and teleosts and the intraretinal vessels of mammals which are all felt to be alternative methods of bringing nutrients to the inner retina. PMID- 7887489 TI - Retinal pigment epithelial fine structure in the American crow (Corvus brachyrhynchos). AB - The fine structure of the retinal epithelial (RPE) region has been investigated by light and electron microscopy in the American crow (Corvus brachyrhynchos). In this species the RPE consists of a single layer of cuboidal cells which display numerous deep basal (scleral) infoldings and plentiful apical (vitreal) microvillar processes which surround photoreceptor inner and outer segments. The RPE cells are joined laterally by a series of tight junctions (Verhoeff's membrane) located in the mid to basal region. Within the epithelial cells, smooth endoplasmic reticulum is very abundant while rough endoplasmic reticulum (RER) is scarce. Mitochondria of various shapes are abundant basally while polysomes are plentiful and widespread. In the light-adapted state RPE nuclei are large and vesicular and basally located while the melanosomes of these cells are predominantly located with the apical processes indicating photomechanical movements. Myeloid bodies are large and numerous and often have ribosomes on their outer surface. Bruch's membrane (complexus basalis) is typical of avian species in that it is pentalaminate and the lamina densa is displaced near the choriocapillaris. The endothelium of the choriocapillaris is thin facing Bruch's membrane but is only moderately fenestrated. Some of these fenestrations display a double-layered diaphragm while the majority show the more typical single layered diaphragm noted in most species. PMID- 7887490 TI - Retinal photoreceptor fine structure in the American crow (Corvus brachyrhynchos). AB - The morphology of the light-adapted retinal photoreceptors of the American crow (Corvus brachyrhynchos) has been investigated by light and electron microscopy. They consist of rods, single cones and double (unequal) cones present in a ratio of about 4:3:3 respectively. The rods are stout cells with a long inner segment and an outer segment that reaches to the RPE cell body. In the light-adapted state, the pigment-laden apical processes of the RPE cells surround cell photoreceptor types for most of their length. The rod inner segment displays an ellipsoid of mitochondria, a large hyperboloid of glycogen, much RER, numerous polysomes, Golgi zones and autophagic vacuoles. Single cones show a slightly tapered outer segment, a large and usually heterogeneous oil droplet and an ellipsoid of mitochondria at the apex of the inner segment. Double cones consist of a longer, stouter chief member which displays a more homogeneous oil droplet and a prominent paraboloid of glycogen and a slightly shorter and thinner accessory member with no oil droplet or paraboloid. Both members of the double cone as well as the single cones show a prominent ellipsoid and plentiful polysomes, RER and Golgi zones in the inner segment. Along the length of the contiguous membranes of the two members of the double cone are presumed interreceptor junctions. All cone photoreceptors are relatively small in diameter and hence are tightly packed. Judging by their morphology in the light-adapted state neither rods nor cones are felt to undergo photomechanical movements in this species. Rods and cones (both types) display both invaginated (ribbon) synapses as well as numerous flat (conventional) synaptic sites. PMID- 7887492 TI - Purkinje cell compartments in the reeler mutant mouse as revealed by Zebrin II and 90-acetylated glycolipid antigen expression. AB - The cerebellum is organized into a series of parasagittally aligned bands that may be revealed histologically in the adult mouse by largely complementary immunostaining of Purkinje cells sets with the monoclonal antibodies Zebrin II (ZII; antigen:aldolase C) and P-path (PP; antigen:90-acetyl glycolipids). We compared the normal staining pattern using these markers and an antibody to calbindin with that found in the reeler mutants (rl/rl), in which most Purkinje cell migration is halted beneath the cerebellar white matter. The results revealed that Purkinje cells in reeler mutants, despite their ectopic location in large subcortical masses, show a clear tendency to distribute into alternating zones that either stain for Zebrin II or for P-path, with variable transition zones of mixed labeling. However, the estimated number of zones was fewer than in the normal adult cortex: roughly 7-9 zones are revealed per side in the mutant compared with 14 major divisions in wild type mice. These results raise the possibility that neurons destined to express these markers are segregated during their migration and that the final phase of migration into the cortex might involve further splitting or interdigitation between cell sets expressing the two antigens. PMID- 7887493 TI - Cholinesterases and peanut agglutinin binding related to cell proliferation and axonal growth in embryonic chick limbs. AB - Embryonic cholinesterases are assigned important functions during morphogenesis. Here we describe the expression of butyrylcholinesterase and acetylcholinesterase, and the binding of peanut agglutinin, and relate the results to mitotic activity in chick wing and leg buds from embryonic day 4 to embryonic day 9. During early stages, butyrylcholinesterase is elevated in cells under the apical ectodermal ridge and around invading motoraxons, while acetylcholinesterase is found in the chondrogenic core, on motoraxons and along the ectoderm. Peanut agglutinin binds to the apical ectodermal ridge and most prominently to the chondrogenic core. Measurements of thymidine incorporation and enzyme activities were consistent with our histological findings. Butyrylcholinesterase is concentrated near proliferative zones and periods, while acetylcholinesterase is associated with low proliferative activity. At late stages of limb development, acetylcholinesterase is concentrated in muscles and nonexistent within bones, while butyrylcholinesterase shows an inverse pattern. Thus, as in other systems, in limb formation butyrylcholinesterase is a transmitotic marker preceding differentiation, acetylcholinesterase is found on navigating axons, while peanut agglutinin appears in non-invaded regions. These data suggest roles for cholinesterases as positive regulators and peanut agglutinin-binding proteins as negative regulators of neural differentiation. PMID- 7887494 TI - Chick gonadogenesis following early surgical bursectomy. II. Ultrastructural data on the embryonic left and right female gonads. AB - We examined the ultrastructural characteristics of the medullary steroidogenic cells in left and right female gonads of surgically bursectomized chick embryos killed on the 17th day of incubation. The steroidogenic cells of the bursectomized embryos have a more developed system of cisternae in the smooth endoplasmic reticulum than controls, and their mitochondria show some alterations in the density of the matrix and in the shape of the cristae. On the basis of these results, an enhancement of the steroidogenic activity in both gonads is suggested. PMID- 7887491 TI - Retinoic acid in limb-bud outgrowth: review and hypothesis. AB - Limb outgrowth is arguably the most fundamental aspect of limb development. It begins with the emergence of buds from the embryo's lateral body wall. More rapid growth along each bud's proximodistal axis than along its anteroposterior or dorsoventral axes yields the limb's basic elongated shape. Many processes that generate refinements of this basic limb form are now being explored at the molecular level. Yet, there remain gaps in our understanding of basic limb outgrowth itself. This review examines the pivotal role of the apical ectodermal ridge in promoting and maintaining limb-bud outgrowth. It discusses the interplay between the apical ectodermal ridge and the subridge limb mesenchyme. It examines evidence that the pattern of limb anomalies in the offspring of mothers exposed to exogenous retinoids such as retinoic acid strongly suggests interference with apical ectodermal ridge function. It covers evidence that cellular retinoic acid binding protein in the cytoplasm of the cells under the apical ectodermal ridge limits the effects of retinoic acid, a potent retinoid and teratogen, on retinoic acid-driven gene transcription. It explains that retinoic acid generally enhances differentiation in a variety of cell types. On the basis of the information presented, it is suggested that the limb ectoderm promotes cellular retinoic acid binding protein expression in the subridge mesenchyme and thereby limits the access of retinoic acid to its nuclear receptors in these cells. Cellular retinoic-acid-binding-protein-mediated, local sequestration or inactivation of free retinoic acid is suggested as a prerequisite not only for the continued responsiveness of the distal mesenchyme to growth promotion by the apical ectodermal ridge, but to the maintenance of the apical ectodermal ridge itself by the subridge mesenchyme. PMID- 7887495 TI - A possible explanation for the response characteristics of multi-tooth periodontal ligament mechanoreceptors in the cat. AB - During the course of a study on the morphology of periodontal ligament mechanoreceptors it was observed that a direct relation, without intervening bone, existed between the mandibular canine and first premolar tooth roots in the cat. An area, representing a window in the alveolar septal bone, extended 2-3 mm from the apex towards the tooth crown. Ruffini nerve terminals were observed amongst the collagen bundles in the ligament between the roots of the two teeth. Light and electron microscopy were used to identify the receptors. It is proposed that a periodontal ligament mechanoreceptor can respond to forces applied to adjacent teeth; movement of both teeth need not occur. This may explain the observation made in the past that single periodontal ligament mechanoreceptors respond to forces applied to more than one tooth. PMID- 7887496 TI - Immunoreactivity for phosphorylated 200-kDa neurofilament subunit is heterogeneously expressed in human sympathetic and primary sensory neurons. AB - This study was undertaken to investigate whether human sensory and sympathetic neurons contain phosphorylated neurofilament proteins, and whether they may be classified on the basis of this property, as in other mammalian species. The distribution of the phosphorylated 200-kDa neurofilament protein subunit (p200 NFP) was investigated in lumbar sympathetic and dorsal root ganglia by means of the RT97 monoclonal antibody (against p200-NFP). The intensity of immunostaining, and the size of neuronal body profiles were measured in order to define different neuron subclasses. In dorsal root ganglia, most of the neuronal profiles (96%) were p200-NFP immunoreactive, and the intensity of immunostaining was not related to neuronal perikarya size. In the lumbar paravertebral sympathetic ganglia, virtually all neurons displayed p200-NFP immunoreactivity, and the intensity of immunolabelling was also independent of the size of the neuronal somata. These results demonstrate heterogeneity in the expression of p200-NFP immunoreactivity in human sympathetic and sensory neurons. In contrast to other mammalian species, RT97 immunolabelling cannot be used as a discriminative marker for the two main types of human primary sensory neurons. On the other hand, our findings provide evidence for the occurrence of phosphorylated neurofilaments within peripheral neuron cell bodies. PMID- 7887497 TI - Oocyte structure in dominant and subordinate follicles in zebu cattle (Bos indicus). AB - The objective of the study was to investigate the light and ultrastructural morphology of dominant and subordinate oocytes from zebu (Bos indicus) cattle. Healthy cycling animals, which had a well-developed corpus luteum as judged by rectal palpation, were administered cloprostenol to induce luteolysis and therefore ovulation. The animals were slaughtered at days 3-11 post-ovulation, but those slaughtered at days 8-11 received a second injection of cloprostenol at day 7. Cumulus-oocyte complexes were aspirated from the largest (dominant) and the second largest (subordinate) follicles, and processed for transmission electron microscopy. Up to day 7, the dominant oocyte presented a peripherally located spherical oocyte nucleus with a compact dense fibrillar nucleolus. After day 7, the nuclear envelope became undulated and the nucleolus vacuolated. The nuclei contained an average of four nucleoli. In addition to vesicles, mitochondria, smooth endoplasmic reticulum, Golgi complexes and cortical granules, the ooplasm contained annulate lamellae and microtubules. Moreover, mitochondrial granules and pleomorphic forms of mitochondria were commonly observed. Some subordinate oocytes exhibited advanced stages of meiotic maturation. It is concluded that (1) the dominant oocyte undergoes certain prematurational changes, including nucleolus vacuolation, in the period from luteolysis up to the presumptive occurrence of the LH peak and (2) subordinate oocytes may undergo meiotic maturation. PMID- 7887498 TI - A cytochemical study of the nucleolus and nucleolus-related structures during human spermatogenesis. AB - Besides the components of typical nucleoli, three other nuclear structures were identified in spermatogonia by positive silver staining: dense centers, fibrillar regions, and dense granules. There was a close relationship between the dense centers and fibrillar regions in spermatogonia and spermatocytes, whereas the dense granules, which appeared dispersed throughout the nucleoplasm of spermatogonia, became localized at the periphery of chromosomes in spermatocytes. From the beginning of spermiogenesis, these three structures then appeared in direct relationship with the dense fibrillar component of the nucleolus. At the Golgi phase, a new nuclear structure also appeared in close relationship with the dense fibrillar component. As it was morphologically similar to the fibrillar region, but not silver stained, it was designated fibrillar structure. With further spermatid development, as the dense fibrillar component gradually disappeared, a sharp increase in the number of the associated dense granules was observed; these granules then disappeared as well. In spermatids at cap phase, each fibrillar region appeared intimately associated with several fibrillar structures. In maturing spermatids, silver staining became confined to the fibrils that appeared located inside the nuclear vacuole. The nuclear vacuole also contained a dense fibrillar structure in intimate relationship with these fibrils and the peripheral condensed chromatin. Ethidium bromide-PTA, Na tungstate and EDTA regressive staining suggest the presence of RNP in the fibrillar regions, dense granules and intravacuolar fibrils, and the presence of DNP in the fibrillar structures. PMID- 7887499 TI - The placenta and cardiac foramen ovale of the babirusa (Babyrousa babyrussa). AB - The structures of the placenta and the cardiac foramen ovale of the babirusa (Babyrousa babyrussa) were studied by means of light and scanning electron microscopy, with material from eleven fetal and neonatal animals. The babirusa has a diffuse epitheliochorial placenta. The chorion of the term placenta is fusiform in shape, and most of its surface comprises rows of villi interrupted by round, oval or irregularly shaped aerolae. A network of fetal placental capillaries indents the epithelial layer covering the tops and sides of the interareolar villi. The round and oval areolae have slender, irregularly shaped villi. The irregular areolae have undulating surfaces without villi. The umbilical cord contains two arteries, one vein and the urachus. The foramen ovale, when viewed from the terminal part of the caudal vena cava has the appearance of a tunnel; a fold of tissue projects from the caudal edge of the foramen ovale into the lumen of the left atrium. This fold, the distal end of which is straight-edged, constitutes a large proportion of the tube, the remainder being formed by the atrial septum. Comparison of the anatomy of the placenta and heart with those of members of the Suidae and Hippopotamidae indicates that the babirusa has more characters in common with the pigs than with the hippos. PMID- 7887500 TI - Increases in the number of cells in different areas of epithelial somites related to changes in morphology and development. AB - There are two distinct groups of cells in the epithelial somite: cells in the epithelial ball that form the periphery, and loose mesenchymal cells found in the central cavity (somitocoele). Recent work has produced evidence to show that these two groups of cells have significant differences (morphology, origin, fibronectin content, reaction to peanut lectin, communication properties) but the significance of these differences has yet to be established. It is not yet clear whether the epithelial somite stage of development is merely a time for cell proliferation, or whether it is a time when significant differences develop which have consequences in subsequent morphogenesis. Certainly, there are indications that the two groups of cells might form different structures related to the vertebral column based on their position in the subsequent sclerotome. In this study, we have examined the number of cells that are present in both the epithelial ball and the somitocoele at various stages of maturity. The results show that later-formed somites contain significantly more cells in both the epithelial ball and the somitocoele. Furthermore, while the density of cells in the epithelial ball remains constant (accounting for an increase in dimensions of the somite), there is a significant increase in density of cells in the somitocoele. This suggests that there is an important distinction being created between the cells of the epithelial ball and those in the somitocoele.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887501 TI - Fine structure of the retinal pigment epithelium in the Port Jackson shark (Heterodontus phillipi). AB - The structure of the retinal epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) has been studied by light and electron microscopy in the Port Jackson shark (Heterodontus phillipi). In this elasmobranch the RPE consists of a single layer of low cuboidal cells which show basal (scleral) infolding and apical (vitreal) processes that enclose photoreceptor outer segments. Laterally these epithelial cells are joined by a series of apically located tight junctions. The RPE cells display a large vesicular nucleus, abundant smooth endoplasmic reticulum as well as numerous polysomes and mitochondria. Phagosomes are present, rough endoplasmic reticulum is scarce and myeloid bodies were not observed. Melanosomes are absent over the choroidally located tapetum lucidum, but are not abundant even in extratapetal areas. This paucity of melanosomes probably makes retinomotor movements unimportant. Bruch's membrane or complexus basalis is a pentalaminate structure. The endothelium of the choriocapillaris is thin but minimally fenestrated. PMID- 7887502 TI - Ontogeny of the endocrine cells of the stomach of sea bass (Dicentrarchus labrax L.): an ultrastructural study. AB - The endocrine cells present in the developing stomach of sea bass larvae have been characterized ultrastructurally. Only one endocrine cell type (type I) was found in the presumptive stomach of 9- and 12-day-old larvae, one (type II) and five (types III, IV, V, VI and VII) in the aglandular stomach of 32-, and of 39- to 46-day-old larvae, respectively, and five (types III, VIII, IX, X and XI) in the differentiated stomach of 55- and 60-day-old larvae. A maturation process was established for some of these cells. Types I, II and III and types IV and X were thought to be different maturational stages of the same endocrine cell type. PMID- 7887503 TI - Comparison of peritoneal fluid analysis before and after exploratory celiotomy and omentopexy in cattle. AB - The effect of right paralumbar fossa exploratory celiotomy and omentopexy on peritoneal fluid constituents was studied in 22 adult dairy cows. Six cows were eliminated on the basis of physical examination findings (n = 2), surgical findings (n = 2), or inability to obtain a sufficient volume of peritoneal fluid (n = 2). Sixteen cattle had normal results of CBC and serum biochemical analysis, and a minimum of 1 ml of peritoneal fluid was obtained by abdominocentesis. Abdominocentesis was repeated on days 1, 2, and 6 after surgery. Statistical analysis for repeated measures was performed, using a significance level of P < 0.05. Stage of gestation was evaluated for interaction with time. Mean total nucleated cell count was 3,200 cells/microliters before surgery, was significantly increased 2 days after surgery (16,336 cells/microliters), and continued to increase through day 6 (20,542 cells/microliters). Mean polymorphonuclear cell count was 1,312 cells/microliters before surgery and was significantly higher at 2 (11,043 cells/microliters) and 6 (10,619 cells/microliters) days after surgery. Mean lymphocyte count was 254 cells/microliters before surgery and was significantly increased 2 days (1,911 cells/microliters) after surgery. By day 6, lymphocyte numbers were similar to preoperative values. Mean mononuclear cell count was 770 cells/microliters before surgery and was significantly increased on days 1 (3,084 cells/microliters), 2 (3,285 cells/microliters), and 6 (2,349 cells/microliters) after surgery. Mean eosinophil numbers were 1,388 cells/microliters before surgery and were significantly increased on day 6 (6,347 cells/microliters) only. Interaction between time and stage of gestation was found only for specific gravity and total protein concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887504 TI - Critical appraisal of pressure-frequency relation for estimation of diaphragm function in conscious calves. AB - A method yielding functional diaphragmatic variables in conscious animals is crucially needed to determine whether concepts and conclusions drawn from deeply anesthetized, highly instrumented clinically normal animals can be extrapolated to patients. Transdiaphragmatic pressure (Pdi) was, therefore, measured in 20 conscious calves during supramaximal transvenous bilateral stimulations of the phrenic nerves (pulse duration, 0.2 milliseconds; pulse frequency, 1, 10, 20, 30, 40, 70, and 100 Hz). Constancy of phrenic activation and precontraction length and geometry was ensured by respectively monitoring the amplitudes of right and left mass action potentials and triggering each activation train at end expiratory lung volume against an occluded airway. Repeated phrenic activation and pressure recording procedures were well tolerated, safe, specific, and able to achieve constant and symmetric diaphragmatic tetanic contractions for prolonged periods. The Pdi increased with frequency of stimulation, so that, at 10, 20, 40, and 70 Hz, the mean +/- SD generated Pdi was 33 +/- 5, 65 +/- 8, 82 +/- 6, and 94 +/- 6% of Pdi at 100 Hz, respectively. The general shape of the Pdi frequency relation and the absolute values of the generated Pdi were reproducible at 10-hour intervals despite CO2- or resistor-induced substantial changes in breathing pattern. It is concluded that this experimental model provides a reliable assessment of diaphragm function in conscious animals and can be used to study diaphragmatic contractility. PMID- 7887505 TI - Production of Salmonella serogroup D (O9)-specific enzyme-linked immunosorbent assay antigen. AB - Serologic testing to detect persistent IgG titer directed at Salmonella lipopolysaccharide (LPS) has proven useful in detecting Salmonella carrier cattle without clinical signs of disease and in seroepidemiologic studies. Although little cross-reactivity exists between most Salmonella serogroups, groups B (O1, 4 [5], 12) and D (O1, 9, 12) share somatic (LPS cell wall) antigens O1 and O12, which results in some cross-reactions. This may be unimportant in most instances, because group-B and group-D carriers need to be identified and culled. It may be desirable in some situations, such as when trying to control S dublin, to determine which serogroup is present in a given herd. For this reason, a procedure to produce a pure O9 group-D antigen was developed. Salmonella dublin (group D) was grown by use of standard procedures, and LPS was extracted by use of the phenol-water method. The LPS was then oxidized with sodium periodate, dialyzed, reduced with sodium borohydride, cleaved with hydrochloric acid, and again dialyzed. This procedure successfully cleaved the saccharides comprising O antigens 1 and 12, leaving a pure O9 ELISA antigen. Sera from cattle vaccinated or naturally infected with S typhimurium, S agona, and S schwarzengrund (all group B), S montevideo (group C1), and S dublin (group D) were tested by ELISA, using modified and unmodified antigens. When the ELISA antigen used was the chemically modified (pure O9) group-D antigen, elimination of cross-reactions confirmed the structural loss of cross-reacting O1 and O12 antigens. PMID- 7887506 TI - Evaluation of the single-injection plasma disappearance of technetium-99m mercaptoacetyltriglycine method for determination of effective renal plasma flow in dogs with normal or abnormal renal function. AB - Effective renal plasma flow (ERPF) was evaluated, using continuous-infusion p aminohippurate clearance (CLPAH) and single-injection plasma clearance of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3; CLMAG3) methods. Simultaneous clearance determinations were made in 6 dogs: 2 determinations for each dog before, and 1 determination after renal failure was induced by administration of amphotericin B. Linear regression analysis was used to derive an equation to estimate ERPF from CLMAG3 after the single IV injection. A Student's t-test was used to compare pharmacokinetics between the dogs when they were healthy and when they were in renal failure. An F-test was used to determine the appropriate Student's t-test. Results indicated that CLMAG3 correlated reasonably well (r = 0.83, P < 0.0001) with ERPF obtained from the CLPAH value. The volume of distribution and elimination of 99mTc-MAG3 decreased during renal failure. Although there was minimal binding of 99mTc-MAG3 to erythrocytes, it was significantly (P = 0.0008) lower during renal failure. Protein binding was not significantly different during renal failure. All dogs had signs of nausea and emesis at variable times after injection of 99mTc-MAG3. Determination of CLMAG3 after a single injection provides an adequate means to rapidly assess ERPF in dogs. The technique could easily be performed in dogs with renal disease, thus providing valuable information regarding progression of naturally acquired renal failure. PMID- 7887507 TI - Quantitative renal scintigraphic determination of effective renal plasma flow in dogs with normal and abnormal renal function, using 99mTc mercaptoacetyltriglycine. AB - Effective renal plasma flow (ERPF) was evaluated, using the measurement of p aminohippurate clearance (CLPAH) and quantitative renal scintigraphy (QRS) with 99mTc-mercaptoacetyltriglycine (99mTc-MAG3). The CLPAH and QRS determinations were made in 6 dogs: 2 determinations for each dog before, and 1 determination after induction of renal failure by administration of amphotericin B. Least squares regression analysis was used to derive an equation to estimate ERPF from QRS data. The results indicated that QRS, using 99mTc-MAG3, correlated reasonably well (r = 0.82, P < 0.001) with ERPF determined from the CLPAH value. The right kidney contributed 53.3% of global ERPF (P = 0.002). Hepatobiliary excretion of 99mTc-MAG3 was variable within each dog. There was not a consistent pattern with respect to time or renal function. All dogs had nausea or emesis, or both, after IV administration of 99mTc-MAG3. The QRS method with 99mTc-MAG3 provides an adequate means to estimate ERPF in healthy dogs and dogs with renal failure. PMID- 7887508 TI - Effects of subject stance time and velocity on ground reaction forces in clinically normal greyhounds at the trot. AB - Force plate gait analysis was used to study the effects of subject stance time and velocity on ground reaction forces in 6 adult Greyhounds at the trot. Data for 210 valid trials were obtained. Stance time negatively correlated with velocity (r = -0.85 for the forelimbs, r = -0.61 for the hind limbs), decreasing as velocity increased. Stance time in the forelimbs and hind limbs correlated more closely with changes in vertical peak force and impulse than did velocity. The trials were divided into 3 distinct velocity ranges (V1 = 1.5 to 1.8 m/s, V2 = 2.1 to 2.4 m/s, and V3 = 2.7 to 3.0 m/s), 3 distinct forelimb stance time ranges (FST1 = 0.144 to 0.176 second, FST2 = 0.185 to 0.217 second, and FST3 = 0.225 to 0.258 second), and 3 distinct hind limb stance time ranges (HST1 = 0.105 to 0.132 second, HST2 = 0.139 to 0.165 second, and HST3 = 0.172 to 0.198 second). Peak forces increased as velocity increased and decreased as stance time increased. Vertical impulse decreased as velocity increased and increased as stance time increased. The relation between stance time, subject velocity, and ground reaction forces was documented for clinically normal Greyhounds at the trot. Changes in stance time accurately reflected changes in subject velocity and ground reaction forces in clinically normal dogs and could be used to normalize trial data within a sampling period. PMID- 7887509 TI - Effects of subject stance time and velocity on ground reaction forces in clinically normal greyhounds at the walk. AB - Force plate gait analysis was used to study the effects of subject stance time and velocity on ground reaction forces in 5 adult Greyhounds at the walk. Data from 146 valid trials were obtained. Stance time and velocity were linearly related, and stance time had a strong, negative correlation with velocity (r = 0.72 for the forelimbs, r = -0.56 for the hind limbs). Stance time correlated more closely with changes in peak vertical force and impulse than did velocity. Stance time and velocity correlated less strongly with braking and propulsion forces and impulses. The trials were divided into 2 distinct velocity ranges (V1 = 0.92 to 1.03 m/s, V2 = 1.06 to 1.17 m/s), 2 distinct forelimb stance time ranges (FST1 = 0.40 to 0.48 second, FST2 = 0.50 to 0.55 second), and 2 distinct hind limb stance time ranges (HST1 = 0.40 to 0.45 second, HST2 = 0.46 to 0.51 second). Five trials from each dog were included in each range, and the mean values were used to evaluate changes in ground reaction forces between groups. Peak vertical force in the forelimbs decreased significantly (P = 0.048) as FST increased; however, difference was not detected in vertical force between velocity groups. Peak vertical force in the hind limbs decreased significantly (P = 0.001) as HST increased and increased significantly (P = 0.000) as velocity increased. Differences were not observed between groups in forelimb or hind limb braking and propulsive forces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887510 TI - Comparison of in vivo and in vitro corticotropin-releasing hormone-stimulated release of proopiomelanocortin-derived peptides in cats. AB - In 6 cats, the effect of IV administration of various concentrations of ovine corticotropin-releasing hormone (oCRH) on plasma concentrations of cortisol, alpha-melanocyte-stimulating hormone (alpha-MSH), and adrenocorticotropic hormone (ACTH) was measured. After administration of 1.0 microgram of oCRH/kg of body weight, significant (P < 0.05) increases in plasma cortisol, alpha-MSH, and ACTH concentrations were observed. After administration of 0.1 microgram of oCRH/kg, significant increases were found only for cortisol and ACTH concentrations. In vitro release of ACTH from dispersed feline pars distalis cells in primary culture stimulated by oCRH and arginine vasopressin (AVP) was dose-dependent. Maximal stimulation was achieved by 1 nM oCRH or 100 nM AVP. The oCRH-stimulated ACTH release was partially inhibited by dexamethasone, and AVP-induced release was completely inhibited. Pars intermedia cells released 20 times as much alpha MSH as ACTH. A dose-dependent inhibition of alpha-MSH release was induced by the dopamine agonist, bromocriptine. This inhibition could be partially abolished by coincubation with haloperidol. Bromocriptine had no effect on release of ACTH. In conclusion, oCRH stimulates the pars distalis and pars intermedia of the pituitary gland of cats. Release of ACTH is stimulated by a direct effect on the pars distalis. In addition, in cats, oCRH is a more potent secretagogue than is AVP. The MSH release from the pars intermedia is sensitive to dopaminergic inhibition, indicating that dopamine may have a central role in regulation of MSH secretion in cats. PMID- 7887511 TI - Consideration of anatomic and radiographic features of the caudal pouches of the femorotibial joints of horses for the purpose of arthroscopy. AB - Development of an arthroscopic approach to the caudal pouches of the equine stifle has been necessary because cranial approaches do not allow access to articular lesions in the caudal aspect of the joint. Therefore, the anatomy of the caudal region was examined in 52 cadaver limbs by use of gross dissection (29), x-ray-computed tomography (6), fluoroscopy (8), or arthroscopy (9). Additionally, using arthroscopic techniques developed in equine cadaver limbs, 3 stifles from 2 anesthetized horses were arthroscopically explored. Fluoroscopy was used to verify needle placement for joint injection and filling patterns of each femorotibial joint. The medial femorotibial joint sac (n = 4) held a mean +/ SD 41.67 +/- 5.77 ml of injection fluid, and the lateral femorotibial joint sac (n = 4) held a mean 61.67 +/- 2.89 ml of injection fluid. Vital structures that inadvertently could be damaged during arthroscopy of the caudal pouches of the stifle included the peroneal nerve (located approx 7 cm caudal to the lateral collateral ligament), the popliteal artery and vein (situated directly between the medial and lateral femoral condyles), and the lateral femoral condyle (most often traumatized during arthroscopy). The tendon of the popliteus muscle, which is contiguous with the joint capsule of the caudal pouch of the lateral femorotibial joint, made arthroscopic exploration of this pouch particularly difficult. PMID- 7887512 TI - Immunomodulatory effects of staphylococcal antigen and antigen-antibody complexes on canine mononuclear and polymorphonuclear leukocytes. AB - Staphylococcal antigens and immune complexes (IC) prepared from antigen and hyperimmune canine serum were tested for their effects on certain functions of mononuclear (MN) and polymorphonuclear (PMN) leukocytes (cells) obtained from healthy dogs. The effect on MN cells was studied by determining the ability of antigen or IC to augment or inhibit mitogenesis induced by phytohemagglutinin (PHA). The effect of antigen or IC on PMN cells was studied by measurement of H2O2 production as an indicator of respiratory burst. Neither the antigen nor the IC, when cultured with MN cells, was mitogenic. Coincubation of antigen or IC with MN cells and PHA resulted in a concentration-dependent decrease in mitogenesis. The decreased mitogenesis could not be overcome by addition of excess PHA, and may in part have been related to toxic effects of the antigen or IC on MN cells. When MN cells were instead preincubated with antigen or IC, then washed and stimulated with PHA, there was still a concentration-dependent inhibition of mitogenesis, although toxicity to the cells was not observed. Low concentrations of staphylococcal antigen or IC stimulated slight H2O2 production by PMN cells. When PMN cells were coincubated with IC and another stimulus (opsonized zymosan or phorbol myristate acetate), IC appeared to augment phorbol myristate acetate-, but not zymosan-induced stimulation. These results suggest that staphylococcal antigens, either alone or complexed with antibody, have the ability to stimulate PMN cells and inhibit MN cell function. Such actions may have a role in the pathogenesis of recurrent staphylococcal infection in canine patients. PMID- 7887513 TI - Prevalence of aerobic bacteria in bronchoalveolar lavage fluids from healthy pigs. AB - Fiberoptic bronchoscopy was performed in pigs to assess bacterial contamination of bronchoalveolar lavage fluids (BALF) obtained by use of the method and to determine the aerobic bacterial species in bronchoalveolar airways of healthy pigs. Bacterial contamination of BALF caused by insertion of the bronchoscope was evaluated, using a chromogenic bacterial tracer strain, and was found to be 0.22% of total colony-forming units (CFU), with range between 0 and 1.6%. A total of 164 pulmonary-healthy pigs from 6 closed herds were selected. The BALF obtained from these pigs were examined bacteriologically. Bacteria could not be isolated from 10.4% of all BALF; 5.5% of the BALF samples yielded pure cultures; and 84.1% yielded mixed aerobic bacterial growth. In BALF from 29.2% of the pigs, < or = 5 x 10(2) CFU of bacteria/ml were isolated. The total number of bacteria in BALF from 50% of the pigs varied between 5 x 10(2) and 10(3) CFU/ml; 10.4% of BALF samples contained between 10(3) CFU/ml and 5 x 10(3) CFU/ml. More than 1 bacterial species were isolated from a single lung lavage of 84.1% of the pigs. Up to 6 species were isolated from a single BALF sample. A total of 443 bacterial isolates were differentiated into 25 bacterial genera and species. Samples of BALF yielded staphylococci (67.6%: Staphylococcus hyicus from 13.4% of the samples and S aureus from 2.4%), alpha-hemolytic streptococci (49.4%), Escherichia coli (42.1%), non-hemolytic streptococci (26.2%), Klebsiella spp (18.3%), micrococci (12.8%), and Coryneformes (11.0%). Other bacterial species were found, but less frequently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887514 TI - Characterization of an Actinobacillus pleuropneumoniae seeder pig challenge exposure model. AB - Five strains of Actinobacillus pleuropneumoniae serotype 1 were used to intranasally infect 5 groups of pigs. Using each bacterial strain, infected pigs (termed seeder pigs) were commingled for 48 hours with 5 groups of noninfected test pigs, then were removed. Seeder and test pigs were maintained in isolation and were observed for 14 days. Seeder pigs had mortality that was threefold greater than that of test pigs (24% vs 8%). Rectal temperature in excess of 40.3 C was achieved for 84% of test pigs and 88% of seeder pigs. Neither of these 2 variables was statistically different between the 2 groups of pigs. Clinical impression scores > or = 2 (on a 0 to 3 scale) were three-fold (64% vs 20%) greater for seeder than for test pigs (P < 0.05). The total number of bacterial isolations or nonrecoverable isolates was tabulated for test and seeder pigs' lungs at necropsy, irrespective of the amount of lesions. The number of A pleuropneumoniae isolations was not statistically different between test and seeder pig populations. Recovery of Pasteurella multocida or other bacteria was greater from the seeder pigs (P < 0.05), whereas the number of non-recoverable isolates was greater from test pigs than from seeder pigs (P < 0.05). Assessment of lung lesions at necropsy by either visual estimation or on a weight basis were in agreement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887515 TI - Characterization of a pseudorabies virus that is defective in the early protein 0 and latency genes. AB - A recombinant pseudorabies virus that is defective in the early protein 0 (EP0) and large latency transcript (LLT) genes was constructed. A portion of the EP0 and LLT genes was replaced by the lacZ gene of Escherichia coli that had been placed under the control of the pseudorabies virus gX gene promoter. This recombinant virus produces smaller size plaques and yields less virus than does the parent virus on Madin-Darby bovine kidney cells. Although the time course of virus replication and release into the medium of the recombinant and parent viruses are similar, the recombinant virus did not reach as high a titer. Similar to the parent virus, the recombinant virus replicates in the upper segment of the respiratory tract of swine, but the amount of progeny viruses produced is significantly reduced. The data indicated that the EP0 and LLT genes of pseudorabies virus are nonessential for replication. Virus that lacks these 2 genes has impaired growth in tissue culture and is attenuated for swine, compared with the parent virus. PMID- 7887516 TI - Characterization of a murine monoclonal antibody generated against Neospora caninum tachyzoites by use of western blot analysis and immunoelectron microscopy. AB - A murine monoclonal antibody (MAB) 6G7 generated against tachyzoites of Neospora caninum recognized 8 major and several minor antigens, as observed by western blot analysis. Relative rate of migration of the 8 major antigens ranged from 31 to 97.4 kd. In addition, MAB 6G7 recognized a Toxoplasma gondii tachyzoite antigen with a relative rate of migration of 107 kd. Immunogold labeling of N caninum tachyzoites grown in human foreskin fibroblast cells indicated that MAB 6G7 binds to micronemes, dense granules, basal portions of rhoptries, and intravacuolar tubules within the parasitophorous vacuole. Monoclonal antibody 6G7 also bound to micronemes and basal portions of rhoptries within tachyzoites of T gondii. Monoclonal antibody 6G7 did not significantly inhibit development of tachyzoites in vitro. PMID- 7887517 TI - Pathologic findings of experimentally induced Streptococcus uberis infection in the mammary gland of cows. AB - Twenty-five quarters of 12 dairy cows, 3 to 8 years old, with a bacteriologic history of freedom from infection with Streptococcus uberis were inoculated via the teat canal with S uberis (23 quarters) or sterile medium (2 quarters). The cows were sent to slaughter 1, 3, or 6 days later. Acute inflammatory response involving accumulation of large numbers of polymorphonuclear, neutrophilic leukocytes (neutrophils) in the secretory acini was recognized after 24 hours in infected cows. After 6 days, the neutrophil response was still evident, but infiltration of septa by lymphocytes, septal edema, extensive vacuolation of secretory cells, focal necrosis of alveoli, small outgrowths of the secretory and ductular epithelium, and widespread hypertrophy of the ductular epithelium also were recognized. Early stages of involution and fibrosis also were evident at that stage. Streptococci were identified by immunoperoxidase labeling, free or phagocytosed, in macrophages; in the alveolar lumina, adherent to damaged secretory or ductular epithelium; in the subepithelium and septal tissue; and in lymphatic vessels and lymph nodes. The importance of the macrophage as the primary phagocytic cell is highlighted, and doubt is cast on the value of the exuberant neutrophil response by the host in defense of the gland. PMID- 7887518 TI - Effect of topically applied 2% pilocarpine and 0.25% demecarium bromide on blood aqueous barrier permeability in dogs. AB - The effect of topically applied 2% pilocarpine and 0.25% demecarium bromide on aqueous humor flare was evaluated while treating normal eyes of dogs 3 times daily for 8 days. Fifteen clinically normal Beagles were allotted to 2 drug treatment groups, and flare was measured, using laser flaremetry. Pilocarpine caused an increase of flare to 167 photon counts (pc)/ms at 7 hours, compared with the nontreated control eye mean value 3.7 pc/ms. By 31 hours, flare had decreased to 70 pc/ms with 3 daily topical treatments. By 55 hours, the flare measurement was in the normal range. Intraocular pressure (IOP) decreased in the treated eyes, compared with the non-treated eyes, and maximal decrease in IOP was observed at the same time as maximal flare. Demecarium induced a similar increase in flare and decrease in IOP, with peak effect seen at 31 hours. At that time, the flaremetry result was 28 pc/ms, compared with 3.4 pc/ms in the nontreated control eyes. After 8 days of 3 times daily treatment, flare values had returned to normal in eyes of dogs in both treatment groups. The transient increase in aqueous humor protein concentration did not result in ocular or visual damage, and long-term changes were not seen. The amount of flare increase attributable to topical application of pilocarpine was greater than the increase in human eyes when measured by use of laser flaremetry. PMID- 7887519 TI - Prospective randomized comparison of intravenous versus subcutaneous administration of radioiodine for treatment of hyperthyroidism in cats. AB - One hundred twenty cats with hyperthyroidism were treated with radioiodine (131I); 60 cats were administered radioiodine SC, and 60 cats were administered radioiodine IV. Before treatment, radioactive tracer studies were performed on each cat to determine peak radioactive iodine uptake and effective half-life. These data were used to calculate the dose of radioiodine that would have to be given to each cat to deliver 150 Gy to the thyroid tissue. The 2 groups of cats were similar with regard to age, tracer study results, and radioiodine dose. Mean estimated thyroid mass was larger for cats treated IV, but mean serum thyroxine concentration was higher for cats treated SC. Route of administration did not affect thyroidal uptake of radioiodine. However, radiation exposure of personnel was significantly lower with SC administration than with IV administration, even when IV catheterization was performed Eighty-five percent of cats treated IV and 84% of cats treated SC were euthyroid 4 years after treatment. Six percent of the cats became hypothyroid after treatment. When compared with IV administration, SC administration of radioiodine appeared to be as effective for treatment of hyperthyroidism, safer to personnel, and less stressful to the cats. PMID- 7887520 TI - Effect of succinylcholine, diazepam, and dantrolene on the urethral pressure profile of anesthetized, healthy, sexually intact male cats. AB - Effects of the neuromuscular blocking agent succinylcholine (n = 9), the centrally acting skeletal muscle relaxant diazepam (n = 11), and the directacting skeletal muscle relaxant dantrolene sodium (n = 8) on the urethral pressure profile were evaluated in anesthetized, healthy, sexually intact, adult male cats. Intravenous administration of succinylcholine (0.075 mg/kg of body weight) significantly decreased mean absolute pressure in the prostatic and post prostatic/penile intraurethral segments by -9.5 and -6.5 mm of Hg, respectively (P = 0.0002 and P = 0.0006, respectively). Dantrolene (1.0 mg/kg, IV) significantly decreased mean prostatic and postprostatic/penile intraurethral segmental pressures by -3.5 and -2.8 mm of Hg, respectively (P = 0.005 and P = 0.0181, respectively). Diazepam (0.8 mg/kg, IV) did not significantly alter mean intraurethral segmental pressures. None of the drugs caused a change in segmental lengths of the urethra. These results indicate that skeletal muscle makes a substantial contribution to intraurethral tone in anesthetized, healthy, sexually intact male cats and that skeletal muscle relaxation may be successful in reducing prostatic and post-prostatic/penile urethral segmental tone in male cats. These results also suggest that dantrolene sodium may be valuable for the pharmacologic management of urethral disorders in male cats. PMID- 7887521 TI - Changes in renal function associated with treatment of hyperthyroidism in cats. AB - We measured glomerular filtration rate (GFR) estimated by plasma disappearance of 99mTc-labeled diethylenetriaminepentaacetic acid, serum concentrations of thyroxine (T4), creatinine, and urea nitrogen, and urine specific gravity in 13 cats with naturally acquired hyperthyroidism before and 30 days after treatment by bilateral thyroidectomy, and in a group of 11 control cats. Mean (+/- SD) serum T4 concentration decreased from a pretreatment value of 120.46 (+/- 39.21) nmol/L to a posttreatment value of 12.15 (+/- 6.26) nmol/L (P < 0.0001; reference range, 10 to 48 nmol/L). Treatment of hyperthyroidism resulted in a decrease in mean (+/- SD) glomerular filtration rate, from 2.51 (+/- 0.69) ml/kg of body weight/min to a posttreatment value of 1.40 (+/- 0.41) ml/kg/min (P < 0.0001). Mean serum creatinine concentration increased from 1.26 (+/- 0.34) mg/dl to 2.05 (+/- 0.60) mg/dl (P < 0.01). Mean serum urea nitrogen concentration increased from 26.62 (+/- 6.83) mg/dl to a mean postthyroidectomy concentration of 34.92 (+/- 8.95) mg/dl (P < 0.01). All changes were significant. Two cats developed overt renal azotemia after treatment of hyperthyroidism. Our results provide further evidence that treatment of hyperthyroidism can result in impaired renal function. In addition, our results suggest that, in some instances, thyrotoxicosis might mask underlying chronic renal insufficiency. PMID- 7887522 TI - Densitometric properties of long bones in dogs, as determined by use of dual energy x-ray absorptiometry. AB - We performed dual-energy x-ray absorptiometry (craniocaudal and lateromedial views) on 10 pairs of humeruses, radiuses, femurs, and tibias from dogs, using an alignment jig, to determine the homotypic bone mineral density variations of long bones. The bones were divided into 3 regions: proximal, middle, and distal parts of the diaphysis. The bone mineral density of cortical bone, medullary bone, and total bone was determined. Of 160 homotypic comparisons, 21 indicated significant (P < or = 0.05) differences between right and left bones at either a region or location. These differences were observed most frequently in the craniocaudal view and were probably secondary to positioning errors. Evaluation of elliptical bones, such as the radius, also indicated that, when the thicker dimension, such as the lateromedial view of the radius was measured, the bone mineral density of regions-of-interest in that view was greater than that in the opposite view (ie, craniocaudal view of the radius). This study validates the concept of using the contralateral limb as the control condition in orthopedic studies of dogs, particularly when evaluating the densitometric properties of long bones. This study also emphasizes the importance of accurate positioning to prevent inadvertent alteration of bone mineral density results when using dual-energy x ray absorptiometry. Dual-energy x-ray absorptiometry is particularly susceptible to positioning errors, because it converts a 3-dimensional structure into a 2 dimensional image. PMID- 7887523 TI - Administration of ochratoxin A and T-2 toxin to growing swine. AB - Effects of dietary ochratoxin A (OA) and T-2 toxin, fed singly and in combination, were evaluated in growing crossbred pigs. Thirty-six barrows (3 replicates of 3 for each of 4 treatment groups, mean body weight, 18.0 kg) were fed: 0 mg of OA and 0 mg of T-2/kg of feed (control); 2.5 mg of OA/kg of feed; 8.0 mg of T-2/kg of feed; or 2.5 mg of OA plus 8.0 mg of T-2/kg of feed; for 30 days. Production performance, serum biochemical, hematologic, immunologic, and pathologic evaluations were made. Body weight and body weight gain were decreased by all toxin treatments, but the combination toxin treatment reduced weight gain more than did either of the toxins administered singly and could be considered additive. Liver weight was decreased by combination treatment, whereas kidney weight was increased by OA treatment. Ochratoxin decreased serum cholesterol, inorganic phosphorus, and alkaline phosphatase values; reduced mean cell volume, hemoglobin concentration, and macrophage phagocytosis; and increased creatinine and total protein values. Consumption of T-2 toxin reduced hemoglobin and serum alkaline phosphatase values. The combination treatment decreased serum cholesterol, gamma-glutamyltransferase, alkaline phosphatase, mean cell volume, hematocrit, and hemoglobin values, as well as lymphoblastogenesis and phagocytosis, and increased serum creatinine concentration. We concluded that OA and T-2, singly or in combination, can affect clinical performance, serum biochemical, hematologic, and immunologic values, and organ weights of growing barrows. Although some analytes were affected more by the combination than by either toxin alone, the interactions could best be described as additive, not synergistic. PMID- 7887524 TI - Efficacy of 4-methylpyrazole for treatment of ethylene glycol intoxication in dogs. AB - 4-Methylpyrazole (4-MP), an alcohol dehydrogenase inhibitor, was administered to dogs to treat ethylene glycol (EG) intoxication. Eleven dogs were given 10.6 g of EG/kg of body weight; 5 dogs were treated with 4-MP 5 hours after EG ingestion and 6 dogs were treated with 4-MP 8 hours after EG ingestion. 4-Methylpyrazole was administered IV as a 50-mg/ml [corrected] solution in 50% polyethylene glycol: initial dose, 20 mg/kg; at 12 hours after initial dose, 15 mg/kg; at 24 hours after initial dose, 10 mg/kg; and at 30 hours after initial dose, 5 mg/kg. Physical, biochemical, hematologic, blood gas, serum and urine EG concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, 72 hours, and at 1 week and 2 weeks after EG ingestion. Dogs of both groups developed clinicopathologic signs associated with EG intoxication, including CNS depression, hyperosmolality, high anion gap metabolic acidosis, polydipsia, polyuria, calcium oxalate monohydrate and dihydrate crystalluria, and isosthenuria. Fractional excretion of sodium was increased in all dogs between 1 and 9 hours after EG ingestion, but remained increased beyond 24 hours only in the 2 dogs treated at 8 hours after EG ingestion that developed acute renal failure. All dogs treated 5 hours after EG ingestion recovered without morphologic, biochemical, or clinical evidence of renal impairment. Of the 6 dogs treated 8 hours after EG ingestion, 2 developed acute renal failure. One of the dogs treated 8 hours after EG ingestion remained isosthenuric for 2 months, but did not manifest any other signs of renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887525 TI - Comparison of ethanol and 4-methylpyrazole as treatments for ethylene glycol intoxication in cats. AB - The efficacy of 4-methylpyrazole (4-MP) and ethanol as treatment for ethylene glycol (EG) intoxication in cats was compared. Twenty-two cats were assigned at random to 6 experimental groups. Cats of 1 experimental group were given only 4 MP; those of another experimental group were given only EG. Cats of 3 experimental groups were intoxicated with EG and given 4-MP at 0 hour or 2 or 3 hours after EG ingestion, and those of 1 experimental group were given EG and treated with ethanol 3 hours after EG ingestion. Physical, biochemical, hematologic, blood gas, serum and urine EG concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, and 72 hours, 1 weeks, and 2 weeks after EG ingestion or 4-MP treatment in cats of the 4-MP only group. The half-life of EG and percentage of ingested EG excreted unchanged were determined for each group. 4-Methylpyrazole treatment at 0 hour was most effective at preventing metabolism of EG. 4-Methylpyrazole was not effective in preventing development of renal failure when given 2 or 3 hours after EG ingestion. Ethanol given 3 hours after EG ingestion was successful in preventing development of renal dysfunction in 2 of the 6 cats treated 3 hours after EG ingestion. Of the remaining 4 cats treated with ethanol, 2 developed transient renal dysfunction and 2 developed acute oliguric renal failure and were euthanatized. 4 Methylpyrazole given 2 or 3 hours after EG ingestion was less effective in preventing EG metabolism than was ethanol given 3 hours after EG ingestion. Therefore 4-MP, at the dose found to be effective in dogs, cannot be recommended as an alternative to ethanol for treatment of EG intoxication in cats. PMID- 7887526 TI - Percutaneous endoscopic gastrostomy: a community hospital experience. AB - Percutaneous endoscopic gastrostomy (PEG) is a well established procedure for establishing a feeding port in patients unable to take oral nutrition. As these patients are often elderly with multiple ailments, mortality due to comorbidities is common. This retrospective study reviewed the experience with PEG in a community hospital, with particular attention paid to morbidity and mortality rates. Randomly selected charts of 100 patients who had PEG performed at our hospital between 1987 and 1991 were examined. These records were reviewed for patients' age, gender, indications, intraoperative complications, and final disposition. Procedure-related morbidity was defined as any untoward event or death that could not be directly attributed to the patient's primary disease process. The sample consisted of 33 males and 67 females whose ages ranged from 47 to 102 years, with a mean of 82 years. The most common indications were malnutrition (n = 48) and dysphagia due to neurological problems (n = 38). The only procedure-related intraoperative complication involved a patient with uncomplicated umbilical hernia who developed strangulation. The morbidity rate was 4% and the 30-day mortality rate was 16%. Only one death was directly related to the PEG tube, and a second death was possibly related to the PEG tube. This community hospital's experience with PEG reveals low morbidity and mortality rates compared to Stamm gastrostomy. These results confirm that PEG is the procedure of choice for providing aging patients with a safe route for enteral nutrition. PMID- 7887527 TI - Colorectal and gynecological malignancies: comparison of B72.3 monoclonal antibody imaging, CT, and serum tumor antigens. AB - Noninvasive B72.3 monoclonal antibody imaging provides beneficial information that may influence therapeutic and surgical decisions, and may clarify other clinical, laboratory, and CT scan findings. Intraoperative localization of tumor sites with a hand-held gamma probe holds promise as a further advantage of this technique. PMID- 7887528 TI - A comparative study of open, laparoscopic intracorporeal, and laparoscopic assisted low anterior resection and anastomosis in pigs. AB - This study was done to investigate whether laparoscopic intracorporeal (LI) or laparoscopic assisted (LA) colon resection results in improved anastomotic healing compared with open colon resection (OR). Thirty-six domestic swine were randomly assigned to undergo either LI, LA, or OR of the rectosigmoid. For OR cases, the sigmoid was resected through a midline incision, and a transanal end to-end stapled anastomosis was constructed with an ILS device. For LA and LI cases, the sigmoid was laparoscopically mobilized and divided distally, using 5 trocar sites. For LA cases, the proximal sigmoid was brought out through an enlarged trocar site and resected; the ILS anvil was secured to the proximal end, and the colon was replaced in the abdominal cavity where the anastomosis was completed by transanal insertion and firing of ILS device. For LI cases, the sigmoid was resected laparoscopically and retrieved through a 33 mm trocar. The ILS anvil was introduced via the same trocar, and the device was laparoscopically secured with two Endoloop (Ethicon Endo-Surgery, Cincinnati, OH) pursestring sutures. The anastomosis was completed the same way as for LA cases. Animals were killed at 7 days, at which time the anastomoses were evaluated by barium enema, bursting pressure, and histologic appearance. There were no radiographic anastomotic leaks. The mean bursting pressure was 205 +/- 65 mmHg for the 13 OR animals, 240 +/- 53 mmHg for 11 LA animals, and 242 +/- 43 mmHg for the 12 LI animals (N.S.). Histologic evaluation for inflammation indicated no significant differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887529 TI - Bicycle trauma: a five-year experience. AB - The medical records of 84 patients who were admitted to the hospital following injuries sustained during bicycle collisions (BC) between January 1986 and December 1991 were retrospectively reviewed. BC most commonly occurred during summer months in the afternoon and early evening. The average patient age was 21.3 years, with more men injured than women (83% vs 17%). Forty-four individuals were struck by a motor vehicle, 36 fell from their cycles, and two were struck by another cyclist. The average ISS for the group was 13.1. Fifteen per cent of the patients had a documented positive toxicology screen; all patients tested positive for ethanol, with an average blood alcohol level of 201 mg/dL. An additional 17% of patients had polychemical intoxication. Orthopedic injuries were the most commonly encountered (59.5%), with lower extremity fractures being most common (52%). Neurologic injuries accounted for 35.7% of injuries, with closed head injuries being most common. Twenty-four patients sustained visceral injuries: 50% thoracic, 25% genitourinary, and 25% abdominal. Of the thoracic injuries, 83% had parenchymal lung injuries, and half had skeletal chest injury. No patient had a vascular lesion within the chest, owing to the minimal deceleration incurred during these injuries. The genitourinary injuries (n = 6) were all urethral injuries that occurred with ejections from the bicycle. No patient had any form of protective gear. The overall average length of stay was 9.15 days, with 30.9% requiring ICU admission. Although bicycling remains a popular recreational activity as well as mode of transportation, few locals mandate protective legislation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887530 TI - Conservative management of pediatric pancreatic pseudocyst using octreotide acetate. AB - Pancreatic pseudocysts in children are rare. A total of 213 cases have been reported in the literature, the majority secondary to trauma (65%). Treatment options range from conservative, non-operative management to operative drainage. Octreotide acetate, a long-acting analog of somatostatin, is a synthetic peptide with a variety of endocrine and gastrointestinal functions. Octreotide has been successfully used following pancreatic surgery to reduce exocrine function and most recently in the management of adult pancreatic pseudocysts. We report the efficacy of octreotide, as an adjunct to treatment, in two children with pancreatic pseudocyst. Each child was treated conservatively with bowel rest, hyperalimentation, and octreotide acetate (2.5 micrograms/kg SQ QD). Complete resolution of the pseudocysts occurred within 5 weeks. We conclude that octreotide acetate is a safe and potentially effective adjunct in the treatment of pediatric pancreatic pseudocyst, and should be added to the management of pseudocyst before drainage procedures. PMID- 7887531 TI - Rupture and hemorrhage of hepatic focal nodular hyperplasia. AB - Although adenoma and focal nodular hyperplasia (FNH) are both benign liver lesions, adenomas are associated with a risk of rupture and malignant degeneration. This had led to the general recommendation of resection of adenomas. However, FNH rarely ruptures or becomes malignant, and a nonoperative approach has been adopted by most hepatobiliary centers when the diagnosis of FNH can be made with reasonable certainty. There are only two previous reports of rupture of FNH in the English literature; we present a third case of FNH with spontaneous rupture and hemorrhage. An 18-year-old healthy Caucasian woman presented with sudden onset of severe RUQ pain. She had never been pregnant, nor used oral contraceptive agents, and had not sustained major trauma. Her abdominal exam revealed RUQ tenderness on palpation. Hepatic biochemical tests, CBC, and coagulation tests were normal. Her hematocrit of 44% fell to 31% over 48 hours. CT scan revealed right anterior lobe and left medial segment hypodense liver lesions (4-5 cm) as well as hemoperitoneum and angiography revealed hypervascular lesions. At laparotomy, two tan fibrous subcapsular masses were excised. Pathology showed a central stellate scar in both lesions with several nodules surrounding the central scar on microscopic section, characteristic of FNH. There was evidence of hemorrhage in one lesion. Significant symptoms are an indication for resection of FNH lesions. However, most patients with FNH are asymptomatic and have a normal physical exam. The natural history of these lesions is enigmatic, and the indications for surgery are still evolving. This report emphasizes that a small risk of rupture clearly exists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887532 TI - Meta-analysis of antibiotics in tube thoracostomy. AB - The use of antibiotics for patients undergoing tube thoracostomy was determined to be highly variable based on a study conducted at a national meeting of surgeons. A meta-analysis of six randomized studies previously reported was performed. The analysis was carried out using the Confidence Profile Method software FAST*PRO. The meta-analysis was structured using dichotomous outcomes of infectious chest processes (empyema, effusion, pneumonia, wound infection, tracheitis, etc.) versus no infectious chest process in patients with and without antibiotics. The effect measures calculated included actual difference in probabilities, relative risk, percent differences in probabilities, and odds ratio. The results of this meta-analysis suggest that antibiotics should be used in patients undergoing tube thoracostomy. Antibiotic selection should maximize therapy for Staph. aureus. The implementation of this practice guideline will require the co-operation of multiple specialty oriented physicians and surgeons. PMID- 7887533 TI - The utility of the CCK DISIDA scan in the treatment of occult biliary tract disease. AB - The vast majority of biliary tract disease is correlated with calculi, and the diagnosis of biliary disease is made simpler when calculi are detected. There are good screening studies for the detection of calculi; however, a reproducible objective test for biliary tract disease in the absence of gallstones has been lacking. Occult biliary tract disease should be considered when symptoms typical of biliary tract disease are present, gallstones cannot be demonstrated, and other diseases have been ruled out. This is characteristically a diagnosis of exclusion, with only the subjective criteria of pain relief to validate surgical intervention. Recently, we have used a nuclear medicine test that simulates the gallbladder response to normal postprandial physiologic stress, to study in an objective fashion the gallbladder function of a group of patients who have symptoms typical of biliary tract disease, but no demonstrable calculi. We have found that the CCK DISIDA study has correlated well with occult pathology. The experience at Easton Hospital has confirmed that the CCK augmented DISIDA scan with calculation of ejection fraction is a reasonably accurate study, with a sensitivity of 88% in detecting previously suspected but undemonstrable pathology in this selected population. This corresponds closely to the observed finding that the pathology reports of 77% of the resected gallbladders noted some abnormality. Of further interest is the long term symptomatic relief achieved in 85% of the patients available for follow up interviews, including a symptomatic benefit in eight of the 11 patients with a normal pathology report.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887534 TI - 1525 laparoscopic cholecystectomies without biliary injury: a single institution's experience. AB - Laparoscopic Cholecystectomy (LC) has become the preferred treatment of gallbladder disease. The indications for LC remain unchanged from those for open cholecystectomy (OC). A total of 1525 patients underwent LC at Georgia Baptist Medical Center between December 1989 and December 1992. The procedure was completed in 1,492 patients (97.8%) and required conversion to OC in 33 patients (2.2%). Selective intraoperative cholangiography was used in 165 patients (10.8%). Overall morbidity was 4.06%, and there were four deaths not operatively related, for a 0.26% mortality rate. There have been no biliary ductal injuries. The average hospital stay was 0.82 days, with 37.4% of the patients going home as true outpatients and 44.5% going home on postop Day one. Most published series on LC report a small incidence of biliary injury. We feel that with meticulous dissection of the cystic duct and use of selective intraoperative cholangiography to define unsure anatomy, biliary injury can be minimized. PMID- 7887535 TI - Outpatient thoracoscopy: a case report and discussion. AB - Thoracoscopy has long been recognized as having significant diagnostic and therapeutic value. We present a new, less invasive method of obtaining good biopsy specimens of pleural based lesions using a single incision and on an outpatient basis. JW, who has a history of Hodgkin's Lymphoma, presents with a suspicious pleural mass adjacent to the AP window and not amenable to percutaneous biopsy. She was admitted to the ambulatory surgery unit and underwent video thoracoscopic biopsy of the lesion through a single 12 mm incision. Surgery time was 25 minutes, and frozen section revealed Hodgkin's lymphoma. No chest tube was inserted, and post-op chest film revealed a small pneumothorax that resolved in 4 hours. The patient was ready for discharge at that time. The technique we used involved placing a standard 10 mm trocar and scope in the midaxillary line with the patient in the lateral decubitus position. Once the scope is in, the trocar is pulled back so that a mediastinal biopsy forcep can be placed alongside the camera through the same hole. The biopsy is taken, and irrigation and cautery instruments can then also be placed and used in a similar manner. Before removing the camera, a prolene pursestring suture is placed around the incision. While the anesthesiologist inflates the lung, the camera is slowly removed, watching all lobes inflate. The pursestring is then tied and the patient awakened. We have performed seven of the above procedures thus far with good results. We feel the following are essential in patient selection for outpatient thoracoscopy: 1) The lesion to be biopsied is pleural based.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887536 TI - Differentiation factors induce expression of muscle, fat, cartilage, and bone in a clone of mouse pluripotent mesenchymal stem cells. AB - Growth factors have been used experimentally to accelerate wound healing by increasing scar tissue formation at a wound site. These studies suggest that stimulation of fibroblastic differentiation and proliferation are essential components of adult tissue repair. Recent studies report the presence of mesenchymal stem cells within granulation tissue and as connective tissue resident stem cells. This suggests that mesenchymal stem cells as well as fibroblasts may contribute to wound healing and repair. To determine the potential for mesenchymal stem cells to contribute to nonfibrogenic tissue repair, a clonal population of murine mesenchymal stem cells was examined with dexamethasone, a general differentiation agent, and muscle morphogenetic protein, a specific differentiation-inducing agent. Dexamethasone induced the expression of phenotypic markers for fat, cartilage, and bone in the stem cells. Muscle morphogenetic protein induced the expression of mRNAs for the muscle specific regulatory genes MyoD1 and myogenin in these cells. These results suggest that pluripotent mesenchymal stem cells within connective tissue compartments and granulation tissue have the potential to contribute to functional tissue restoration, rather than contributing solely to fibrogenic scar tissue formation during tissue repair. PMID- 7887537 TI - Pyloric channel ulcers: management and three-year follow-up. AB - Twenty-five patients with pyloric channel ulcers are presented. They were predominantly males (84%), with a mean age of 54 years. Four patients were operated upon in the initial admission because of gastric outlet obstruction in three and persistent bleeding in one. Twenty-one patients received H2-antagonist treatment (ranitidine 150 mg or cimetidine 400 mg twice a day). Clinical and endoscopic healing rates were 76% and 38% respectively at 6 weeks, and 91% and 85% respectively at 12 weeks of treatment. The recurrence rate at an average of 3 years of follow-up period on maintenance treatment (ranitidine 150 mg or cimetidine 400 mg nightly) was 65%. Three patients were operated upon during the follow-up period due to persistent symptoms in two and recurrence with obstruction in one Surgical procedures were vagotomy + drainage (five patients) and vagotomy + antrectomy (two patients). There were no recurrences in surgically treated patients at an average of 3.5 years of follow-up, and all were graded as Visick I or II. PMID- 7887538 TI - Laparoscopic is not better than open appendectomy. AB - Laparoscopic appendectomy is increasingly being used by general surgeons. The advantages of the procedure over open appendectomy are not as obvious as the advantages of laparoscopic cholecystectomy over open cholecystectomy. This study was a retrospective review of nonrandomized patients of two attending surgeons over the time period 4/11/91 to 2/15/93. Parameters examined included patient age, gender, operating room time, hospital cost, hospital stay, negative appendectomy rate, and wound infection rate. Results showed that there was no difference in the patient age. Gender was significantly different, with the laparoscopic group containing 68% females, whereas the open group contained only 39% (P < 0.01). Operating room time was significantly longer for the laparoscopic group by approximately 18 minutes (P < 0.05). Hospital cost was $1400.00 more expensive for the laparoscopic group (P < 0.05). Hospital stay and wound infection rates were not significantly different. The negative appendectomy rate was 37% for the laparoscopic group and 12% for the open group (P < 0.05). We conclude that laparoscopic is not superior to open appendectomy. PMID- 7887539 TI - The future of general surgery characterized by general surgical chief residents. AB - The future of any specialty in medicine depends in large part on the career choices of its trainees. We obtained data from General Surgery Chief Residents who finished their training in 1990 and compared their attitudes to a similar survey conducted by us in 1985. According to those responses, residents in general surgery continue to choose fellowship training at a time when they no longer perceive an oversupply of general surgeons. This has broad implications for the future of general surgery as a specialty that requires significant change in the structure of our residency programs. PMID- 7887540 TI - Esophagotomy for incarcerated esophageal foreign bodies. AB - Less than 1% of esophageal foreign bodies are irretrievable by endoscopic techniques. Incarcerated esophageal foreign bodies require esophagotomy for removal. A retrospective study was conducted to determine the incidence, predisposing factors, and optimal treatment of incarcerated esophageal foreign bodies. Four of 815 patients (0.5%) with esophageal foreign bodies required esophagotomy for foreign body removal. Two predisposing factors for incarceration were identified, and these factors were related to patient age. Two infants had neglected esophageal foreign bodies that partially migrated through the esophageal wall. In two adults, foreign body size and sharpness were responsible for incarceration. One cervical and three thoracic esophagotomies were done. One thoracic esophagotomy suture line dehiscence occurred. Occult foreign body pressure necrosis may be a factor in esophagotomy suture line leakage. Care is required in esophagotomy closure. Principles established for repair of esophageal perforations are also applicable to esophagotomy closure. PMID- 7887541 TI - Operative cholangiogram: a simple, reliable, inexpensive method. PMID- 7887542 TI - Use of the neutrophil:lymphocyte ratio in the diagnosis of appendicitis. AB - In patients with right lower quadrant pain, the total white cell count is an unreliable predictor of appendicitis. It has been reported that the lymphocyte count can fall in acute appendicitis. This study was undertaken to investigate whether the neutrophil:lymphocyte ratio is a more sensitive indicator than the total leucocyte count. A retrospective study was performed of patients undergoing appendectomy for suspected appendicitis over a 2-year period. A total of 402 patients were identified; histopathology confirmed appendicitis in 367 (91%). Other significant pathology was found in 13 (3.2%). Twenty-two (5.5%) had a histologically normal appendix and recovered uneventfully with no other diagnosis being made. A total of 298 (79%) patients with appendicitis had an elevated preoperative total white cell count. The neutrophil:lymphocyte ratio was calculated for each patient. Using an upper limit of 3.5:1, it was found that 324 (88%) of patients with appendicitis had a ratio equal to or greater than this value. This was significantly different from the proportion with a raised total leucocyte count (P = 0.001). We suggest that the simple calculation of the neutrophil:lymphocyte ratio may provide a parameter that is more sensitive than the total leucocyte count in the prediction of appendicitis. PMID- 7887543 TI - Risk factors for operative morbidity in patients with systemic lupus erythematosus: an analysis of 63 surgical procedures. AB - The surgical morbidity rate of patients with Systemic Lupus Erythematosus is considered very high; however, the experience in the literature is small. This study will determine the rate of surgical morbidity and the existence of predictive factors in patients with such a disease. The medical records of 53 patients with Systemic Lupus Erythematosus who underwent 63 major operations were analyzed retrospectively. The rate and causes of operative morbidity were registered. Univariate and multivariate statistical analysis was performed to ascertain the existence of predictive factors for morbidity. The overall morbidity and mortality were 16% and 6% respectively. Lymphopenia, hypoalbuminemia, increased SGOT and SGPT, urgent indication of operation, the physical status of the American Society of Anesthesiology, as well as a shorter duration of Systemic Lupus Erythematosus showed a significant correlation with operative morbidity in the univariate analysis; high blood urea nitrogen showed marginal significance. Physical status, urgent indication, and blood urea nitrogen remained as significant variables with the multivariate logistic regression analysis. The surgical morbidity rate of these patients may be lower than previously estimated. The physical status, urgency of operation, and level of blood urea nitrogen seemed to be the most useful independent predictors for surgical morbidity risk in patients with Systemic Lupus Erythematosus. PMID- 7887544 TI - Pseudomyxoma peritonei: does a true mucolytic agent exist? In vitro and in vivo studies. AB - Reproducibility of the so-called "mucolytic effect" of the 2%-10% dextrose-water solution is questioned. To test the mucolytic effect of 5% and 10% dextrose-water solutions and to determine what could be a true mucolytic agent, in vitro and in vivo studies were undertaken in two proven pseudomyxoma peritonei cases. In vitro study: Immediately after the mucin jelly was taken out of the peritoneal cavity, the jelly was immersed in various 40 cc solutions including: 1) 5% dextrose water; 2) 10% dextrose-water; 3) normal saline; 4) lactated Ringer; 5) distilled water. The mucolytic effects of these solutions were observed once every hour after vigorous mixing. In vivo study: After completion of the operation, the peritoneal cavity was repeatedly irrigated with massive warm 5% dextrose-water and normal saline solutions in an attempt to dissolve the residual mucin cake and jelly. Neither 5% and 10% dextrose-water solution nor control solutions of normal saline, lactated Ringer, and distilled water could dissolve the mucin jelly in test tubes at 0, 1, 2, and 3 hours. The "claimed" mucolytic agent, 5% dextrose water solution could not facilitate the removal of both mucin jelly and cake in the peritoneal cavity. The 5% dextrose-water solution was not superior to the normal saline solution in terms of mucolytic effect. In the present study, a true mucolytic agent does not exist. Currently, multiple laparotomy for aggressive cytoreduction remains the treatment of choice for pseudomyxoma peritonei. PMID- 7887545 TI - Adult rhabdomyoma: presentation as a cervicomediastinal mass (case report and review of the literature). AB - The adult rhabdomyoma (ARM) is an unusual and extremely uncommon tumor. Only 96 cases have been reported. Adult rhabdomyomas are found most often in the region of the base of the tongue, floor of the mouth, larynx, and pharynx. Uncommon locations include the soft palate, uvula, lip and cheek, orbit, and stomach. One prior case of extension of an ARM from the supraclavicular region into the mediastinum has been described as an incidental finding at autopsy. It is important to be aware of and correctly identify this tumor because total excision may be curative. Follow-up must be long-term, as recurrence can occur after 35 years. The authors present a case of an ARM diagnosed during the evaluation and treatment of a symptomatic mediastinal mass. This ARM was found to involve the esophagus and trachea from the inferior constrictors in the neck to the azygous vein in the mediastinum. This case represents a previously undescribed presentation of an ARM. We present a review of ARM and outline our diagnostic, therapeutic, and follow-up plans. PMID- 7887546 TI - Fine needle aspiration cytology in the diagnosis and management of ectopic breast tissue. AB - Ectopic breast tissue presents as solitary or multiple masses in young women along the milk line. The most common site is in the axilla. This may present a diagnostic problem as lymphadenopathy, either primary or secondary, or other soft tissue tumors that may present in a similar way. Six patients with eight axillary masses suspicious for ectopic breast tissue were evaluated with fine needle aspiration (FNA) cytology. Five aspirates revealed epithelial cells consistent with breast tissue; one showed adipose tissue; and two were non-diagnostic. This information helped prevent surgery in one pregnant and one lactating woman. Therefore, FNA examination is helpful in the diagnosis of management of ectopic breast tissue. PMID- 7887547 TI - A comparison of transabdominal preperitoneal (TAPP) and total extraperitoneal approach (TEPA) laparoscopic herniorrhaphies. AB - There are a variety of accepted techniques for herniorrhaphy. With the advent of laparoscopic general surgery, laparoscopic transabdominal and total extraperitoneal techniques have been added to the many options for repair of the inguinal hernia. From 5/91 to 6/93 we had performed 290 transabdominal preperitoneal (TAPP) laparoscopic herniorrhaphies on 244 adult patients. Due to concerns of potential early and late complications associated with entering the abdominal cavity, we adopted the total extraperitoneal approach (TEPA) for laparoscopic herniorrhaphies in 6/93. Between 6/93 and 12/93, 118 hernias have been repaired in 95 patients using the total extraperitoneal approach. In a retrospective comparison between these two procedures, the recurrence rate is 1.7% (5/290) for TAPP herniorrhaphies and 0% (0/118) for the TEPA. The overall complication rate for TAPP herniorrhaphies was 11.1% and included thigh paresthesias (6), inferior epigastric artery injuries (4), enterotomy (1), bowel obstruction (1), bladder injury (1), and urinary retention (14). The overall complication rate for the TEPA was 3.2% and included bladder injury (1), and urinary retention (2). Mean operative time was similar between these groups (TAPP 81.2 minutes, TEPA-92.9 minutes). PMID- 7887548 TI - The effect of intensive diabetes therapy on the development and progression of neuropathy. The Diabetes Control and Complications Trial Research Group. AB - OBJECTIVE: To examine whether intensive therapy designed to achieve glycemic levels as close to normal as possible prevents or slows the progression of neuropathy when compared with conventional therapy in patients with insulin dependent diabetes mellitus in the Diabetes Control and Complications Trial. DESIGN: Multicenter, randomized, controlled clinical trial. SETTING: 29 U.S. and Canadian clinical centers. PARTICIPANTS: 1441 patients aged 13 to 39 years, of whom 726 had had insulin-dependent diabetes mellitus for 1 to 5 years and had no retinopathy at baseline (primary prevention cohort); 715 had had diabetes for 1 to 15 years and had minimal to moderate nonproliferative retinopathy at baseline (secondary intervention cohort). INTERVENTION: Intensive therapy with three or more daily insulin injections or continuous subcutaneous insulin infusion guided by four or more glucose tests per day compared with conventional therapy with one or two daily insulin injections. RESULTS: Intensive therapy reduced the development of confirmed clinical neuropathy (defined as a history or physical examination consistent with clinical neuropathy confirmed by either abnormal nerve conduction or autonomic nervous system testing) by 64% (95% CI, 45% to 76%) in the combined cohorts after 5 years of follow-up (5% of the intensive therapy group compared with 13% of the conventional therapy group). The prevalence of abnormal nerve conduction and abnormal autonomic nervous system function were reduced by 44% (CI, 34% to 53%) and 53% (CI, 24% to 70%), respectively (26% of the intensive treatment group developed abnormal nerve conduction compared with 46% of the conventional treatment group; 4% of the intensive treatment group had abnormal autonomic nervous system function compared with 9% of the conventional treatment group). Finally, nerve conduction velocities generally remained stable with intensive therapy but decreased significantly with conventional therapy. CONCLUSION: Intensive diabetes therapy markedly delays or prevents the development of clinically manifest diabetic polyneuropathy as confirmed by objective nerve function testing in patients with insulin-dependent diabetes mellitus. PMID- 7887549 TI - Late relapses in patients successfully treated for thrombotic thrombocytopenic purpura. Canadian Apheresis Group. AB - OBJECTIVE: To determine the incidence and timing of relapses in patients who have recovered from an acute episode of thrombotic thrombocytopenic purpura. DESIGN: Clinical follow-up for 3 to 10 years. SETTING: General community outpatient study; patients who had relapse were hospitalized. PARTICIPANTS: 63 of 72 surviving patients who had participated in a randomized study that compared plasma exchange and plasma infusion as treatments for thrombotic thrombocytopenic purpura and for whom continued clinical follow-up was obtained. OUTCOME MEASURES: Recurrence of thrombotic thrombocytopenic purpura as defined by a decrease in platelet count to less than 100 x 10(9)/L and by the onset of microangiopathic hemolytic anemia as identified by erythrocyte fragmentation in a peripheral blood film. RESULTS: 37 of the 63 patients have not had recurrence of thrombotic thrombocytopenic purpura and have remained completely well; 6 patients have not had recurrence but have developed other medical problems; 3 patients have not had recurrence but have residual neurologic defects from the original episode; and 17 patients have had one or more recurrences, occurring 7 months to 8 years after the original episode. As determined by Kaplan-Meier analysis, the projected recurrence rate after 10 years in all surviving patients is 36% (95% CI, 23% to 59%). CONCLUSIONS: More than one third of patients who survive an acute episode of thrombotic thrombocytopenic purpura will have at least one relapse during the following 10 years. PMID- 7887550 TI - Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. AB - OBJECTIVE: To investigate the relation between the quantity of human immunodeficiency virus type 1 (HIV-1) RNA in plasma and the risk for the acquired immunodeficiency syndrome (AIDS) or a decline in the CD4+ T-cell count after seroconversion. DESIGN: Prospective study. PATIENTS: 62 homosexual men with documented HIV-1 seroconversion. SETTING: University outpatient setting. MEASUREMENTS: Clinical status, CD4+ T-cell counts, and plasma and serum samples were obtained every 6 months. Human immunodeficiency virus RNA in plasma was quantitated with a branched-DNA (bDNA) assay. Serum samples were assayed for neopterin, beta 2-microglobulin, and immune complex dissociated HIV-1 p24 antigen. RESULTS: 18 of 62 (29%) men developed AIDS; 21 (34%) had a significant decline in the CD4+ T-cell count without AIDS; and 23 (37%) had a stable CD4+ T cell count. For each participant, HIV-1 RNA results were categorized into one of four groups: 1) detection of HIV-1 RNA (> 1 x 10(4) genome equivalents/mL [Eq/mL]) in all samples; 2) detection in most samples (> or = 50%); 3) detection in fewer than 50% of samples; and 4) detection in none of the samples. Detection of HIV-1 RNA in all or most samples was strongly associated with AIDS (16 of 18 patients) and a decline in the CD4+ T-cell count (13 of 21 patients) compared with a stable CD4+ T-cell count (4 of 23 patients; P < 0.001). Conversely, the absence of HIV-1 RNA (< 1 x 10(4) Eq/mL) in all or most samples was associated with stable CD4+ T-cell counts (19 of 23 patients) and a lower risk for AIDS or decline in the CD4+ T-cell count (10 of 39 patients; P < 0.001). In multivariate analysis of all laboratory values at the seroconversion visit, a plasma HIV-1 RNA level greater than 1 x 10(5) Eq/mL was the most powerful predictor of AIDS (odds ratio, 10.8; P = 0.01). CONCLUSIONS: Plasma HIV-1 RNA is a strong, CD4+ T-cell independent predictor of a rapid progression to AIDS after HIV-1 seroconversion. PMID- 7887551 TI - Risk factors for a positive tuberculin skin test among employees of an urban, midwestern teaching hospital. AB - OBJECTIVE: To determine the prevalence and incidence of and the relative risks for positive tuberculin skin tests among employees of a large, urban teaching hospital. DESIGN: Retrospective cohort study. SETTING: Barnes Hospital, St. Louis, Missouri. PARTICIPANTS: Hospital personnel employed at any time between January 1989 and July 1991. RESULTS: 684 of 6070 employees screened (11.3% [95% CI, 10.4% to 12.1%]) had positive tuberculin skin tests. Factors associated with a positive result were age (odds ratio, 2.02 per decade [CI, 1.87 to 2.18]; P < 0.0001); black race (odds ratio, 1.58 [Cl, 1.26 to 2.00]; P < 0.0001); Asian race (odds ratio, 16.7 [CI, 9.33 to 29.9]; P < 0.0001); Hispanic ethnicity (odds ratio, 9.45 [CI, 3.58 to 25.0]; P < 0.0001); and percentage of low-income persons within the employee's residential postal zone (odds ratio, 1.14 per 10% [CI, 1.05 to 1.23]; P = 0.001). Twenty-nine of 3106 employees who had at least two tests had skin-test conversions (0.93% [CI, 0.60% to 1.3%]); 15 of these conversions (52%) occurred among employees who had no direct contact with patients. Only the percentage of low-income persons within the employee's residential postal zone (odds ratio 1.39 [CI, 1.09 to 1.78]; P = 0.0075) was independently associated with conversion. CONCLUSIONS: The most important associations with a positive tuberculin skin test were older age, minority group status, and the proportion of low-income persons within the employee's residential postal zone. Skin-test conversion was independently associated only with the percentage of low-income persons in the employee's postal zone. Stratifying employees according to degree of contact with patients or according to departmental group was not useful in determining risk for a positive tuberculin skin test or for skin-test conversion. For certain groups of employees, an exposure to tuberculosis in the community probably poses a greater risk than exposure in the hospital setting. PMID- 7887552 TI - Hepatic hepatitis C virus RNA as a predictor of a long-term response to interferon-alpha therapy. AB - OBJECTIVE: To identify predictors of a long-term response to interferon-alpha therapy in chronic hepatitis C and to determine whether hepatitis C virus (HCV) was eradicated in patients with chronic hepatitis C who had a long-term response to therapy. DESIGN: A retrospective analysis. SETTING: In- and outpatient liver clinic of a municipal hospital in Japan. PATIENTS: 47 patients with chronic hepatitis C who responded to interferon-alpha were divided into two groups: 22 patients with a long-term response (serum aminotransferase levels remained normal for > 1 year after therapy) and 25 patients with a short-term response (serum aminotransferase levels increased again after therapy). MEASUREMENTS: Genotyping of HCV, titers of HCV RNA in liver and serum samples (using the reverse transcriptase-polymerase chain reaction), histologic activity index, and liver histologic tests during and 1 year after therapy. RESULTS: Among the 22 long-term responders, HCV RNA was no longer detectable in liver and serum samples of 21 (95%) at the end of therapy and remained undetectable in the serum of 20 (91%) and in the liver of 19 (86%) 1 year after therapy. Liver histologic tests improved substantially immediately after therapy and 1 year after therapy in the long-term responders; however, 18 (82%) of these patients still had mild, chronic hepatitis. Among the 25 short-term responders, HCV RNA was still detected in the liver of 19 (76%) and in the serum of 9 (36%) at the end of therapy. Multivariate logistic regression analysis showed that the persistent presence of hepatic HCV RNA at the end of therapy was the strongest predictor of relapse. CONCLUSION: These findings suggest that HCV infection was eradicated in most of the long-term responders to interferon-alpha therapy because HCV RNA could no longer be detected in their serum and liver samples and because a significant improvement gradually occurred in their liver histologic results. The persistent presence of hepatic HCV RNA at the end of therapy was the most important predictor of relapse. PMID- 7887553 TI - Methotrexate treatment of idiopathic granulomatous hepatitis. AB - OBJECTIVE: To test the efficacy and safety of low-dose oral pulse methotrexate therapy in patients with idiopathic granulomatous hepatitis who had complications of, did not respond to, or refused glucocorticoid therapy. DESIGN: Prospective case study. SETTING: Academic medical center hospital. PATIENTS: Seven patients with biopsy-proven, idiopathic granulomatous hepatitis who could not tolerate or were unresponsive to glucocorticoid therapy. INTERVENTION: Low-dose oral pulse methotrexate, 15 mg/wk. MEASUREMENTS: Temperature, symptoms, dose of concurrent glucocorticoids, biochemical tests of liver function, side effects of methotrexate, and assessment of liver biopsy specimens. RESULTS: All six febrile patients became afebrile within 3 months of starting methotrexate. Fatigue and anorexia improved in all patients. Glucocorticoid therapy was successfully discontinued within 6 months of starting methotrexate in four patients receiving prednisone at entry. Liver biopsy specimens were obtained again after methotrexate therapy and showed absence of granulomas in four of four patients. The minimum effective dose of methotrexate was 0.20 mg/kg body weight per week. No serious adverse effects and no failures to respond to methotrexate therapy were noted in this group of patients. In three patients, methotrexate therapy has been successfully tapered without signs or symptoms of recurrent disease. CONCLUSIONS: Low-dose oral pulse methotrexate was effective in treating patients with granulomatous hepatitis. PMID- 7887554 TI - Trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in cirrhosis: a randomized trial. AB - OBJECTIVE: To assess the efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis and ascites. DESIGN: A randomized controlled trial. SETTING: University affiliated Veterans Affairs medical center. PATIENTS: 60 consecutive patients with cirrhosis and ascites. INTERVENTIONS: Consecutive patients were randomly assigned to receive either no prophylaxis or trimethoprim-sulfamethoxazole, one double-strength tablet daily, five times a week (Monday through Friday). Patient entry was stratified by serum bilirubin (> 51 mumol/L [> 3 mg/dL]), ascitic fluid protein (< 1 g/dL), and serum creatinine (> 177 mumol/L [> 2 mg/dL]) levels to ensure that high-risk patients would be similarly distributed in the two groups. The median duration of follow-up for the study patients was 90 days. MAIN OUTCOME MEASURES: Spontaneous bacterial peritonitis or spontaneous bacteremia as defined by objective criteria. RESULTS: Spontaneous bacterial peritonitis or spontaneous bacteremia developed in 27% (8 of 30) of patients who did not receive prophylaxis compared with 3% (1 of 30) of patients receiving trimethoprim-sulfamethoxazole (P = 0.025). Overall, infections developed in 9 of 30 patients (30%) not receiving prophylaxis and in 1 of 30 patients (3%) receiving trimethoprim-sulfamethoxazole (P = 0.012). Death occurred in 6 of 30 patients (20%) who did not receive prophylaxis and in 2 of 30 patients (7%) who received trimethoprim sulfamethoxazole (P = 0.15). Side effects--particularly, hematologic toxicity- could not be attributed to trimethoprim-sulfamethoxazole in any patient. CONCLUSIONS: Trimethoprim-sulfamethoxazole was efficacious, safe, and cost effective for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis. PMID- 7887555 TI - Literature and medicine: contributions to clinical practice. AB - Introduced to U.S. medical schools in 1972, the field of literature and medicine contributes methods and texts that help physicians develop skills in the human dimensions of medical practice. Five broad goals are met by including the study of literature in medical education: 1) Literary accounts of illness can teach physicians concrete and powerful lessons about the lives of sick people; 2) great works of fiction about medicine enable physicians to recognize the power and implications of what they do; 3) through the study of narrative, the physician can better understand patients' stories of sickness and his or her own personal stake in medical practice; 4) literary study contributes to physicians' expertise in narrative ethics; and 5) literary theory offers new perspectives on the work and the genres of medicine. Particular texts and methods have been found to be well suited to the fulfillment of each of these goals. Chosen from the traditional literary canon and from among the works of contemporary and culturally diverse writers, novels, short stories, poetry, and drama can convey both the concrete particularity and the metaphorical richness of the predicaments of sick people and the challenges and rewards offered to their physicians. In more than 20 years of teaching literature to medical students and physicians, practitioners of literature and medicine have clarified its conceptual frameworks and have identified the means by which its studies strengthen the human competencies of doctoring, which are a central feature of the art of medicine. PMID- 7887556 TI - The role of the physician and the medical profession in the prevention of international torture and in the treatment of its survivors. American College of Physicians. AB - The prevention of torture and the treatment of survivors are issues that concern an increasing number of physicians in their daily work. Every day, thousands of men, women, and children are subjected to violence and are forced to flee their homelands. There are more than 18 million refugees in the world and hundreds of thousands of persons seeking asylum, many of them in the United States. Physicians are often the first to interview these victims of abuse. Torture has serious and long-lasting health consequences. Thus, physicians can play a key role in documenting and preventing many forms of abuse and in treating survivors. In some areas, physicians may become the targets of arrest because of their work as clinicians or as influential members of their communities. They may also face disturbing ethical dilemmas as they witness torture or its results. As members of the medical profession, physicians have an obligation to their peers around the world. This report reviews the current state of physicians' involvement in the prevention of international torture and in the treatment of its victims. We propose ways in which physicians can become involved by caring for survivors of torture and by providing expert testimony on behalf of victims who seek asylum. We discuss how the medical profession complements the efforts of individual physicians by providing an infrastructure to support and guide their work. Medical organizations can adopt and disseminate ethical principles that specifically address human rights and their violation. They can coordinate letter writing networks for human rights, organize or sponsor fact-finding missions, and develop continuing medical education courses on topics such as the identification and treatment of victims of torture. We conclude that physicians can make a difference, both as clinicians and as advocates for the health of the public and the protection of the human rights. The American College of Physicians will continue to advocate for the rights of persons and communities to live in dignity and peace, free of the fear of unjust imprisonment or torture. PMID- 7887557 TI - Perceptions and misperceptions of skin color. AB - Case presentations are part of many clinicians' daily routines. The format for such presentations often involves stating the age, sex, and race of the patient in the opening description. However, although single-word racial labels such as "black" or "white" are of occasional help to the clinician, they are of limited diagnostic and therapeutic help in many routine cases. Because of their broad scope and lack of scientific clarity, these terms often poorly represent information--for example, about genetic risks and perceptions of disease--that they are supposed to convey. In many instances, they are superficial and potentially misleading terms that fail to serve the patient's medical needs. Demoting these terms from the opening line of routine case presentations shows a recognition of their limitations as scientific labels. Our patients will be better served by more detailed explorations of ethnicity, when germane, in the History of Present Illness or Social History sections of the case presentation in question. PMID- 7887558 TI - Literature, humanities, and the internist. PMID- 7887559 TI - Identifying ethnicity in medical papers. PMID- 7887560 TI - Emergency brain resuscitation. A Working Group on Emergency Brain Resuscitation. AB - Past efforts to reverse or limit the effects of acute stroke have been largely unsuccessful, in part because of the inability to evaluate and treat most patients soon after stroke onset. One important factor in the delay of treatment has been the nihilistic attitude of medical personnel, including physicians, toward the need to rapidly evaluate and treat patients with stroke. This is important for non-neurologists because most patients with stroke are cared for by internists, family physicians, and emergency physicians. We present the concept of emergency brain resuscitation as one method of galvanizing and motivating health professionals to take a more proactive and aggressive approach to treating the patient with acute stroke. Laboratory and clinical data support the potential efficacy of emergency brain resuscitation teams, which will use standard and experimental techniques to treat patients with stroke. A cost-benefit analysis suggests that emergency brain resuscitation may lower the costs associated with stroke by reducing length of hospital stay, disability, and lost wages. The formation of pilot programs is a logical first step toward evaluating and refining this concept. PMID- 7887561 TI - From an observer. PMID- 7887562 TI - Risks for bleeding in patients with pulmonary embolism treated with thrombolytic agents. PMID- 7887563 TI - Risks for bleeding in patients with pulmonary embolism treated with thrombolytic agents. PMID- 7887564 TI - Risks for bleeding in patients with pulmonary embolism treated with thrombolytic agents. PMID- 7887565 TI - Risks for bleeding in patients with pulmonary embolism treated with thrombolytic agents. PMID- 7887566 TI - Osteomalacia and phenytoin therapy. PMID- 7887567 TI - Prophylaxis for stress-related gastric hemorrhage. PMID- 7887568 TI - Prophylaxis for stress-related gastric hemorrhage. PMID- 7887569 TI - Cytokines in polymyalgia and giant cell arteritis. PMID- 7887570 TI - Fogging in infrared tympanic and ear thermometry. PMID- 7887571 TI - HLA typing in patients with Wegener granulomatosis. PMID- 7887572 TI - [Crohn disease]. PMID- 7887573 TI - [Crohn disease: etiopathogenesis]. PMID- 7887574 TI - [Laboratory evaluations and activity indexes of Crohn disease]. PMID- 7887575 TI - [Crohn disease: radiology and echography]. PMID- 7887576 TI - [Computerized tomography and magnetic resonance in Crohn disease]. PMID- 7887578 TI - [The use of new steroids in Crohn disease]. PMID- 7887577 TI - [Salicylates in the treatment of Crohn disease]. PMID- 7887579 TI - [The use of immunosuppressors in Crohn disease]. PMID- 7887580 TI - [General principles of surgical treatment of Crohn disease]. PMID- 7887581 TI - [Elective surgical treatment of Crohn disease]. PMID- 7887582 TI - [Perianal Crohn disease: classification and therapy]. PMID- 7887583 TI - [Basic diet in Crohn disease]. PMID- 7887584 TI - [The recurrence of Crohn disease, today]. PMID- 7887585 TI - [DNA ploidy and cell kinetics in cancer of the rectum]. AB - The pathological assessment of rectal cancer remained essentially unchanged for 50 years and it is based mainly on Dukes' classification and histological granding. Alternative methods of classifications have also been developed but, actually, Dukes'taging is the most important prognostic factor. The limit of Dukes' classification is the incomplete discrimination between high risk and low risk patients into the same stages. The measurements of cellular DNA content by flow cytometry is emerging as a prognostic aid in many human tumours. Authors analyze on the basis of their experience on 116 curative operations for the cancer of the rectum, the relationship between tumour's features, CEA, symptoms, recurrences, survival, type of operation and DNA flow cytometry. In 100 cases they studied the percentage of cells in "s" phase. (SPF). Samples of flow cytometry were prepared using paraffin-embedded tumour blocks. The authors didn't find any statistically significant relation among pathological features, staging, ploidy and SPF. Recurrences rate was 16.6% in diploid tumours and 23% in no diploid (p = 0.3). In SPF < 25% it was 18.2% (p = 0.5). 5-year survival was worse in aneuploid patients (p = 0.06). Using Cox' multivariate regression analysis, ploidy has not independent prognostic significance. In conclusion authors consider ploidy a prognostic factor in rectal cancer, but not independent. However, authors conclude that flow cytometry could help in early staging of the disease, especially in preoperative diagnosis. Flow cytometry has a prognostic significance with informations on tumoral biology and could contribute to select patients for adjuvant therapy or different surgical techniques. PMID- 7887586 TI - [Treatment of primary gastric lymphoma in IE/IIE stages]. AB - The primitive gastric lymphoma constitutes 2-5% of malignant gastric neoplasms. The present treatment of such a pathology is not defined, since it seems that this disease deserves a multidisciplinary approach: surgical, chemotherapical, radiotherapical. The authors by means of this study, intend to estimate the results of the therapeutic treatment employed in 18 patients suffering from primitive gastric lymphoma in the stage IE and IIE. From the results obtained by our study, it emerges that in the lymphomata located in the cavity at the stage IE, there takes place the almost total superimposition of the results, in terms of survival to 5 years, in the patients treated surgically and in those treated by chemotherapy. Therefore, in such cases the chemotherapic treatment can be proposed because it is bloodless, the patient appreciates it more and it seems to be accompanied by a very small number of complications. In the patients with lymphomat located in the antrum at the stage IIE, we have obtained good results in terms of survival joining radiotherapy and chemotherapy to surgery, as reported by Moore. Even taking into account the very small number of cases we have considered, we think the primitive gastric lymphoma at the stage IE must be treated by means of chemotherapy, while that one at the stage IIE requires and integrated treatment. PMID- 7887587 TI - [Is intraoperative cholangiography always indicated during videolaparoscopic cholecystectomy?]. AB - Opinion is divided whether intra-operative cholangiography should be performed routinely or on a selective basis during laparoscopic cholecystectomy. The aims of the present study were to assess the safety, utility and indications of intraoperative cholangiography performed during laparoscopic cholecystectomy. 11 operative cholangiograms were attempted in 63 patients who underwent laparoscopic cholecystectomy (17.4%). Duration of post-operative hospitalization and interval to return to full activity were identical in the two groups. Cholangiography increased the duration of operation (mean 20.1 min: p < 0.01) and the total charges for the operation by almost L. 200,000. Cholangiograms were performed successfully in 100% of the patients and changed operative management in 2 patients. There was not false negative or positive study. No complications or deaths occurred that were due to cholangiography. In follow-up ranging from 1-9 months, there has been no clinical evidence of bile duct injury or retained common bile duct stones. The inescapable conclusion is that an absolute indication for performing cholangiography is unclear anatomy of biliary system. Whereas to document the presence of common bile duct stones, intra-operative cholangiography, neither routine nor selective, is needed. Patients who present with clinical or biochemical signs of choledocholithiasis, a history of cholangitis, acute biliary pancreatitis, or an abnormal CBD on sonogram should have preoperative ERCP and ES before contemplated laparoscopic cholecystectomy. Further advances and confidence with laparoscopic CBD exploration may further change the approach to these patients in the future. In this case selective intra operative cholangiography is mandatory. However, additional prospective analysis of this patient subgroup is needed. PMID- 7887588 TI - [Possibility of presymptomatic diagnosis of familial polyposis coli]. AB - Familial polyposis coli (FPC) is an autosomal dominant inherited disease characterized by an incidence of 1:7000-23000 born alive and by an onset of colorectal cancer in all untreated patients. This diagnosis is obtained mostly in presence of symptoms and in a low percentage after a screening, so it would be very important to have a clinical, biochemical or genetic marker to identify the affected subjects before the onset of the colonic polyps. In the last years many Authors have tested the hypertrophy of retinal pigmented epithelium (CHRPE) in the FPC affected families with interesting results. The aim of our study is to evaluate the predictive role of this clinical marker. 87 subjects have been submitted to ophthalmoscopy: 17 FPC affected patients, 40 first degree relatives and 30 no-polyposis colorectal cancer affected patients. The positivity (CHRPE +) was respectively 88.2%, 45% and 0. The first relatives degree aged more than ten years old have been submitted to the rectosigmoidoscopy and 8/9 CHRPE + persons resulted affected, while all CHRPE--examined were healthy. We have analysed the characteristics of CHRPE, its incidence and sensitivity and in FPC affected patients and in their first degree relatives, with positive results. At the end the CHRPE research and in our and in other experiences presents many advantages: low cost, easy feasibility, repeatability, high sensitivity and specificity. We consider that until the advent of valid routinary genetic tests it can be a good clinical marker in FPC affected families. PMID- 7887589 TI - [Local excision of rectal cancer in early phase as an alternative to major surgery]. AB - The authors analyse the role of local excision as curative procedure of low rectal early cancer. In their opinion it's very important to select the patients in accordance with some characteristics of the tumor (site, grading, mobility, depth, size, stage, involvement of locoregional nodes, ploidia). Intrarectal ultrasonography is thought be the most important diagnostic tool, both in preoperative diagnosis and in postoperative follow-up; it has a high sensibility to define the parietal invasion of rectal cancer and to recognize metastatic nodes. They review various surgical techniques used to make local excision by several authors (transsacral approach by Kraske, transsphinteric approach by Mason and transanal approach by Bailey), as well as the alternative methods (surgical diathermy by Strauss, endocavitary irradiation by Papillon and cryosurgery by Heberer). The authors point out the technique of Bailey and coll. is getting the major approvals owing to its simplicity, low mortality and morbidity rates, poor incidence of recurrences and good survival. The most recent therapeutic protocols provide only local excision for the lesions limited into mucosa and submucosa (stage T1), also postoperative radio- and chemotherapy for tumors involving muscolaris propria (stage T2). On the other hand, advanced rectal cancer (stage T3) may be managed best by major operations. Recurrences rates (5-22%) and five-years survival rates (78-90%) are obviously conditioned by tumor features. Finally, the authors reaffirm, with their personal experience as well, the importance of local excision as curative operation for low rectal early cancer, provided that a careful case selection is made in accordance with macro- and microscopical features of the tumor. PMID- 7887590 TI - [Device for intraarterial access for locoregional chemotherapy in hepatic metastasis from colorectal neoplasms (technical note)]. AB - Metastasis are the most common malignant lesions of the liver. Liver is the most common site of visceral metastasis from colo-rectal carcinoma. Only in few patients are the lesions surgically resectable for cure and standard intravenous chemotherapy produces a low response rate. An intrahepatic arterial device for regional chemotherapy is an effective and safe alternative for unresectable liver metastasis from colorectal carcinoma, with a significant improvement on response rates compared with conventional i.v. chemotherapy; a longer survival is also reported in patients receiving intrahepatic therapy, even if the difference is not statistically significant. The catheter is inserted through the gastro duodenal artery and the reservoir is placed in a subcutaneous pocket on the anterior thoracic wall. The Authors discuss indications, implantation technique and complications. Intra-arterial chemotherapy is administered in ambulatorial regimen and scintigraphic scanning and/or epatic ultrasonography are performed every three months to evaluate response rate. Median survival is variable from 12 to 17 months in the different series with response rates (disappeared metastases or tumor-mass reduction over 50%) of 48%-62%. The increased tumor responses reported together with a lower systemic toxicity (compared with systemic therapy) suggest that intra-arterial chemotherapy is a reliable and well tolerated treatment. PMID- 7887591 TI - [Anhepatic rat, technic for reconstruction of venous circulation]. AB - Authors report an experimental model of total hepatectomy in the rat. In this model whole liver was replaced by an autologous vascular prosthesis. On the contrary as reported in other experiences, in this model is maintained the cavo caval flow, with absence of cavo-caval and porta-caval shunts. Anhepatic rats survival not exceeded two hours from surgery. PMID- 7887592 TI - Boty, a long-terminal-repeat retroelement in the phytopathogenic fungus Botrytis cinerea. AB - The phytopathogenic fungus Botrytis cinerea can infect an extremely wide range of host plants (tomato, grapevine, strawberry, and flax) without apparent specialization. While studying genetic diversity in this fungus, we found an element which is present in multiple copies and dispersed throughout the genome of some of its isolates. DNA sequence analysis revealed that the element contained direct, long-terminal repeats (LTRs) of 596 bp whose features were characteristic of retroviral and retrotransposon LTRs. Within the element, we identified an open reading frame with sequences homologous to the reverse transcriptase and RNase H domains of retroelement pol genes. We concluded that the element we had identified was a retroelement and named it Boty. By comparing its open reading frame with sequences from other retroelements, we found that Boty is related to the gypsy family of retrotransposons. Boty was present in numerous strains isolated from grapes and tomatoes but not in isolates from lentils. We propose that Boty-containing and Boty-deficient groups represent two lineages in the population of B. cinerea. PMID- 7887593 TI - Differential importance of trehalose in stress resistance in fermenting and nonfermenting Saccharomyces cerevisiae cells. AB - The trehalose content in laboratory and industrial baker's yeast is widely believed to be a major determinant of stress resistance. Fresh and dried baker's yeast is cultured to obtain a trehalose content of more than 10% of the dry weight. Initiation of fermentation, e.g., during dough preparation, is associated with a rapid loss of stress resistance and a rapid mobilization of trehalose. Using specific Saccharomyces cerevisiae mutants affected in trehalose metabolism, we confirm the correlation between trehalose content and stress resistance but only in the absence of fermentation. We demonstrate that both phenomena can be dissociated clearly once the cells initiate fermentation. This was accomplished both for cells with moderate trehalose levels grown under laboratory conditions and for cells with trehalose contents higher than 10% obtained under pilot-scale conditions. Retention of a high trehalose level during fermentation also does not prevent the loss of fermentation capacity during preparation of frozen doughs. Although higher trehalose levels are always correlated with higher stress resistance before the addition of fermentable sugar, our results show that the initiation of fermentation causes the disappearance of any other factor(s) required for the maintenance of stress resistance, even in the presence of a high trehalose content. PMID- 7887594 TI - Detection of methanotrophic bacteria in environmental samples with the PCR. AB - We designed PCR primers by using the DNA sequences of the soluble methane monooxygenase gene clusters of Methylosinus trichosporium OB3b and Methylococcus capsulatus (Bath), and these primers were found to be specific for four of the five structural genes in the soluble methane monooxygenase gene clusters of several methanotrophs. We also designed primers for the gram-negative methylotroph-specific methanol dehydrogenase gene moxF. The specificity of these primers was confirmed by hybridizing and sequencing the PCR products obtained. The primers were then used to amplify methanotroph DNAs in samples obtained from various aquatic and terrestrial environments. Our sequencing data suggest that a large number of different methanotrophs are present in peat samples and also that there is a high level of variability in the mmoC gene, which codes for the reductase component of the soluble methane monooxygenase, while the mmoX gene, which codes for the alpha subunit of the hydroxylase component of this enzyme complex, appears to be highly conserved in methanotrophs. PMID- 7887595 TI - Isolation of extracellular 28- and 42-kilodalton beta-1,3-glucanases and comparison of three beta-1,3-glucanases produced by Bacillus circulans IAM1165. AB - Bacillus circulans IAM1165 produces three major extracellular beta-1,3-glucanases (molecular masses, 28, 42, and 91 kDa) during the stationary phase of growth. The 28- and 42-kDa enzymes were purified to homogeneity from the culture supernatant in this study. The properties of these two enzymes were examined, together with those of the 91-kDa enzyme previously isolated. The enzymatic properties of the 28- and 42-kDa beta-1,3-glucanases closely resemble each other. The enzymes belong to a category of endo type 1,3-beta-D-glucan glucanohydrolases. The enzymes were active at pH 4.0 to 7.0. The optimum temperature of the reactions was 60 degrees C when laminarin (a soluble beta-1,3-glucan) was used as the substrate at pH 7.0. The enzymes hydrolyzed barley glucan and lichenan (beta-1,3 1,4-glucans) more effectively than laminarin. Of the three enzymes, the 42-kDa enzyme lysed fungal cell walls the most effectively. PMID- 7887596 TI - Development and application of a monoclonal antibody against Thiothrix spp. AB - Historically, methods used to identify Thiothrix spp. in environmental samples have been inadequate because isolation and identification procedures are time consuming and often fail to separate Thiothrix spp. from other filamentous microorganisms. We described a monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) procedure which was used to identify Thiothrix spp. in wastewater, artesian springs, groundwater, and underwater subterranean samples. The ELISA utilized monoclonal antibody T3511 to a species-specific carbohydrate epitope of Thiothrix spp. No cross-reactions were observed among non Thiothrix strains consisting of 12 species and nine genera. In field trials, the ELISA identified 100% of 20 biochemically and cytologically confirmed Thiothrix spp.-containing samples with no false positives. Indirect immunofluorescent microscopy utilizing T3511 was effective for wastewater samples but not for those from natural spring water because of background fluorescence in the latter. In addition, electron micrographs of Thiothrix spp. labeled with T3511-biotin-anti mouse antibody-gold showed that epitope T3511 was intracellular both in laboratory strains and environmental isolates. The minimum level of detection of the ELISA was 0.10 microgram/ml. PMID- 7887597 TI - Biodegradation of naphthalene in aqueous nonionic surfactant systems. AB - The principal objective of this study was to quantify the bioavailability of micelle-solubilized naphthalene to naphthalene-degrading microorganisms comprising a mixed population isolated from contaminated waste and soils. Two nonionic surfactants were used, an alkylethoxylate, Brij 30 (C12E4), and an alkylphenol ethoxylate, Triton X-100 (C8PE9.5). Batch experiments were used to evaluate the effects of aqueous, micellized nonionic surfactants on the microbial mineralization of naphthalene and salicylic acid, an intermediate compound formed in the pathway of microbial degradation of naphthalene. The extent of solubilization and biodegradation under aerobic conditions was monitored by radiotracer and spectrophotometric techniques. Experimental results showed that surfactant concentrations above the critical micelle concentration were not toxic to the naphthalene-degrading bacteria and that the presence of surfactant micelles did not inhibit mineralization of naphthalene. Naphthalene solubilized by micelles of Brij 30 or Triton X-100 in liquid media was bioavailable and degradable by the mixed culture of bacteria. PMID- 7887598 TI - Expression and in vitro assembly of recombinant glutamate dehydrogenase from the hyperthermophilic archaeon Pyrococcus furiosus. AB - The gdhA gene, encoding the hexameric glutamate dehydrogenase (GDH) from the hyperthermophilic archaeon Pyrococcus furiosus, was expressed in Escherichia coli by using the pET11-d system. The recombinant GDH was soluble and constituted 15% of the E. coli cell extract. The N-terminal amino acid sequence of the recombinant protein was identical to the sequence of the P. furiosus enzyme, except for the presence of an initial methionine which was absent from the enzyme purified from P. furiosus. By molecular exclusion chromatography we showed that the recombinant GDH was composed of equal amounts of monomeric and hexameric forms. Heat treatment of the recombinant protein triggered in vitro assembly of inactive monomers into hexamers, resulting in increased GDH activity. The specific activity of the recombinant enzyme, purified by heat treatment and affinity chromatography, was equivalent to that of the native enzyme from P. furiosus. The recombinant GDH displayed a slightly lower level of thermostability, with a half-life of 8 h at 100 degrees C, compared with 10.5 h for the enzyme purified from P. furiosus. PMID- 7887599 TI - Purification and characterization of alpha-L-arabinofuranosidase from Bacillus stearothermophilus T-6. AB - Bacillus stearothermophilus T-6 produced an alpha-L-arabinofuranosidase when grown in the presence of L-arabinose, sugar beet arabinan, or oat spelt xylan. At the end of a fermentation, about 40% of the activity was extracellular, and enzyme activity in the cell-free supernatant could reach 25 U/ml. The enzymatic activity in the supernatant was concentrated against polyethylene glycol 20000, and the enzyme was purified eightfold by anion-exchange and hydrophobic interaction chromatographies. The molecular weight of T-6 alpha-L arabinofuranosidase was 256,000, and it consisted of four identical subunits as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration. The native enzyme had a pI of 6.5 and was most active at 70 degrees C and at pH 5.5 to 6.0. Its thermostability at pH 7.0 was characterized by half lives of 53, 15, and 1 h at 60, 65, and 70 degrees C, respectively. Kinetic experiments at 60 degrees C with p-nitrophenyl alpha-L-arabinofuranoside as a substrate gave a Vmax, a Km, and an activation energy of 749 U/mg, 0.42 mM, and 16.6 kcal/mol, (ca. 69.5 kJ/mol), respectively. The enzyme had no apparent requirement for cofactors, and its activity was strongly inhibited by 1 mM Hg2+. T-6 alpha-L-arabinofuranosidase released L-arabinose from arabinan and had low activity on oat spelt xylan. The enzyme acted cooperatively with T-6 xylanase in hydrolyzing oat spelt xylan, and L-arabinose, xylose, and xylobiose were detected as the end reaction products.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887600 TI - Molecular characterization of a gene encoding extracellular serine protease isolated from a subtilisin inhibitor-deficient mutant of Streptomyces albogriseolus S-3253. AB - An extracellular serine protease produced by a mutant, M1, derived from Streptomyces albogriseolus S-3253 that no longer produces a protease inhibitor (Streptomyces subtilisin inhibitor [SSI]) was isolated. A 20-kDa protein was purified by its affinity for SSI and designated SAM-P20. The amino acid sequence of the amino-terminal region of SAM-P20 revealed high homology with the sequences of Streptomyces griseus proteases A and B, and the gene sequence confirmed the relationships. The sequence also revealed a putative amino acid signal sequence for SAM-P20 that apparently functioned to allow secretion of SAM-P20 from Escherichia coli carrying the recombinant gene. SAM-P20 produced by E. coli cells was shown to be sensitive to SSI inhibition. PMID- 7887601 TI - Relationship between glycocalyx and povidone-iodine resistance in Pseudomonas aeruginosa (ATCC 27853) biofilms. AB - Biofilm-embedded bacteria are generally more resistant to antimicrobial agents than are planktonic bacteria. Two possible mechanisms for biofilm resistance are that the glycocalyx matrix secreted by cells in a biofilm reacts with and neutralizes the antimicrobial agent and that the matrix creates a diffusion barrier to the antimicrobial agent. This study was therefore conducted to examine the relationship between glycocalyx and enhanced povidone-iodine resistance in biofilms of Pseudomonas aeruginosa (ATCC 27853). Biofilms were generated by inoculation of polycarbonate membranes with broth-grown cells and incubation of them on the surfaces of nutrient agar plates. The quantities of glycocalyx material per cell were found not to be significantly different between biofilm and planktonic samples. Transmission electron microscopy showed that the distributions of glycocalyx material around cells differed in biofilm and in planktonic samples. Addition of alginic acid to planktonic cell suspensions resulted in a slight increase in resistance to povidone-iodine, suggesting some neutralizing interaction. However, the iodine demands created by biofilm and planktonic samples of equivalent biomass were not significantly different and, therefore, do not explain the contrast in resistance observed between biofilm and planktonic samples. Examination of the relationship between cell death and biomass detachment from the glycocalyx matrix revealed that most cell death occurred in the fraction of biomass that detached from a biofilm during treatment. The overall rate of iodine diffusion through biofilms was not different from that of planktonic cells collected on a polycarbonate membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887602 TI - Characterization and environmental regulation of outer membrane proteins in Xenorhabdus nematophilus. AB - We have examined the production of the outer membrane proteins of the primary and secondary forms of Xenorhabdus nematophilus during exponential- and stationary phase growth at different temperatures. The most highly expressed outer membrane protein of X. nematophilus was OpnP. The amino acid composition of OpnP was very similar to those of the porin proteins OmpF and OmpC of Escherichia coli. N terminal amino acid sequence analysis revealed that residues 1 to 27 of the mature OpnP shared 70 and 60% sequence identities with OmpC and OmpF, respectively. These results suggest that OpnP is a major porin protein in X. nematophilus. Three additional proteins, OpnA, OpnB, and OpnS, were induced during stationary-phase growth. OpnB was present at a high level in stationary phase cells grown at 19 to 30 degrees C and was repressed in cells grown at 34 degrees C. OpnA was optimally produced at 30 degrees C and was not present in cells grown at lower and higher temperatures. The production of OpnS was not dependent on growth temperature. In contrast, another outer membrane protein, OpnT, was strongly induced as the growth temperature was elevated from 19 to 34 degrees C. In addition, we show that the stationary-phase proteins OpnA and OpnB were not produced in secondary-form cells. PMID- 7887603 TI - Biological degradation of resin acids in wood chips by wood-inhabiting fungi. AB - Resin acids in many pulp mill effluents are primary sources of toxicity to fish. Inconsistent biological detoxification of chlorinated and nonchlorinated resin acids in secondary treatment of pulp mill effluents is a continuing source of concern. An alternative approach to effluent detoxification is to remove or modify the toxic compounds present in wood chips prior to pulping. Results from experiments in which lodgepole pine sapwood chips were inoculated with several fungal candidates indicate that the total resin acid content can be reduced by up to 67% after fungal growth. Such a treatment could be an efficient and environmentally acceptable way for deresinating wood chips and so decreasing the toxicity of pulp mill effluents. PMID- 7887604 TI - A di- and tripeptide transport system can supply Listeria monocytogenes Scott A with amino acids essential for growth. AB - Listeria monocytogenes takes up di- and tripeptides via a proton motive force dependent carrier protein. This peptide transport system resembles the recently cloned and sequenced secondary di- and tripeptide transport system of Lactococcus lactis (A. Hagting, E. R. S. Kunji, K. J. Leenhouts, B. Poolman, and W. N. Konings, J. Biol. Chem. 269:11391-11399, 1994). The peptide permease of L. monocytogenes has a broad substrate specificity and allows transport of the nonpeptide substrate 5-aminolevulinic acid, the toxic di- and tripeptide analogs, alanyl-beta-chloroalanine and alanyl-alanyl-beta-chloroalanine, and various di- and tripeptides. No extracellular peptide hydrolysis was detected, indicating that peptides are hydrolyzed after being transported into the cell. Indeed, peptidase activities in response to various synthetic substrates were detected in cell extracts obtained from L. monocytogenes cells grown in brain heart infusion broth or defined medium. The di- and tripeptide permease can supply L. monocytogenes with essential amino acids for growth and might contribute to growth of this pathogen in various foods where peptides are supplied by proteolytic activity of other microorganisms present in these foods. Possible roles of this di- and tripeptide transport system in the osmoregulation and virulence of L. monocytogenes are discussed. PMID- 7887605 TI - Identification of a PutP proline permease gene homolog from Staphylococcus aureus by expression cloning of the high-affinity proline transport system in Escherichia coli. AB - The important food-borne pathogen Staphylococcus aureus is distinguished by its ability to grow at low water activity values. Previous work in our laboratory and by others has revealed that proline accumulation via transport is an important osmoregulatory strategy employed by this bacterium. Furthermore, proline uptake by this bacterium has been shown to be mediated by two distinct transport systems: a high-affinity system and a low-affinity system (J.-H. Bae, and K. J. Miller, Appl. Environ. Microbiol. 58:471-475, 1992; D. E. Townsend and B. J. Wilkinson, J. Bacteriol. 174:2702-2710, 1992). In the present study, we report the cloning of the high-affinity proline transport system of S. aureus by functional expression in an Escherichia coli host. The sequence of the staphylococcal proline permease gene was predicted to encode a protein of 497 amino acids which shares 49% identity with the PutP high-affinity proline permease of E. coli. Analysis of hydropathy also indicated a common overall structure for these proteins. PMID- 7887606 TI - Adhesion of germlings of Botrytis cinerea. AB - Adhesion of conidia and germlings of the facultative plant parasite Botrytis cinerea occurs in two distinct stages. The first stage, which occurs immediately upon hydration of conidia and is characterized by relatively weak adhesive forces, appears to involve hydrophobic interactions (R. P. Doss, S. W. Potter, G. A. Chastagner, and J. K. Christian, Appl. Environ. Microbiol. 59:1786-1791, 1993). The second stage of adhesion, delayed adhesion, occurs after viable conidia have been incubated for several hours under conditions that promote germination. At this time, the germlings attach strongly to either hydrophobic or hydrophilic substrata. Delayed adhesion involves secretion of an ensheating film that remains attached to the substratum upon physical removal of the germlings. This fungal sheath, which can be visualized by using interference-contrast light microscopy, scanning electron microscopy, or atomic force microscopy, is 25 to 60 nm thick in the region immediately adjacent to the germ tubes. Germlings are resistant to removal by boiling or by treatment with a number of hydrolytic enzymes, 2.0 M periodic acid, or 1.0 M sulfuric acid. They are readily removed by brief exposure to 1.25 N NaOH. A base-soluble material that adheres to culture flask walls in short-term liquid cultures of B. cinerea is composed of glucose (about 30%), galactosamine (about 3%), and protein (30 to 44%). PMID- 7887607 TI - Cloning, nucleotide sequence, and transcriptional analysis of the Pediococcus acidilactici L-(+)-lactate dehydrogenase gene. AB - Recombinant plasmids containing the Pediococcus acidilactici L-(+)-lactate dehydrogenase gene (ldhL) were isolated by complementing for growth under anaerobiosis of an Escherichia coli lactate dehydrogenase-pyruvate formate lyase double mutant. The nucleotide sequence of the ldhL gene predicted a protein of 323 amino acids showing significant similarity with other bacterial L-(+)-lactate dehydrogenases and especially with that of Lactobacillus plantarum. The ldhL transcription start points in P. acidilactici were defined by primer extension, and the promoter sequence was identified as TCAAT-(17 bp)-TATAAT. This sequence is closely related to the consensus sequence of vegetative promoters from gram positive bacteria as well as from E. coli. Northern analysis of P. acidilactici RNA showed a 1.1-kb ldhL transcript whose abundance is growth rate regulated. These data, together with the presence of a putative rho-independent transcriptional terminator, suggest that ldhL is expressed as a monocistronic transcript in P. acidilactici. PMID- 7887608 TI - Conservation of the genes for dissimilatory sulfite reductase from Desulfovibrio vulgaris and Archaeoglobus fulgidus allows their detection by PCR. AB - The structural genes for dissimilatory sulfite reductase (desulfoviridin) from Desulfovibrio vulgaris Hilden-borough were cloned as a 7.2-kbp SacII DNA fragment. Nucleotide sequencing indicated the presence of a third gene, encoding a protein of only 78 amino acids, immediately downstream from the genes for the alpha and beta subunits (dsvA and dsvB). We designated this protein DsvD and the gene encoding it the dsvD gene. The alpha- and beta-subunit sequences are highly homologous to those of the dissimilatory sulfite reductase from Archaeoglobus fulgidus, a thermophilic archaeal sulfate reducer, which grows optimally at 83 degrees C. A gene with significant homology to dsvD was also found immediately downstream from the dsrAB genes of A. fulgidus. The remarkable conservation of gene arrangement and sequence across domain (bacterial versus archaeal) and physical (mesophilic versus thermophilic) boundaries indicates an essential role for DsvD in dissimilatory sulfite reduction and allowed the construction of conserved deoxyoligonucleotide primers for detection of the dissimilatory sulfite reductase genes in the environment. PMID- 7887609 TI - Degradation and mineralization of atrazine by a soil bacterial isolate. AB - An atrazine-degrading bacterial culture was isolated from an agricultural soil previously impacted by herbicide spills. The organism was capable of using atrazine under aerobic conditions as the sole source of C and N. Cyanuric acid could replace atrazine as the sole source of N, indicating that the organism was capable of ring cleavage. Ring cleavage was confirmed in 14CO2 evolution experiments with [U-14C-ring]atrazine. Between 40 and 50% of ring-14C was mineralized to 14CO2. [14C]biuret and [14C]urea were detected in spent culture media. Cellular assimilation of 14C was negligible, in keeping with the fully oxidized valence of the ring carbon. Chloride release was stoichiometric. The formation of ammonium during atrazine degradation was below the stoichiometric amount, suggesting a deficit due to cellular assimilation and metabolite-N accumulation. With excess glucose and with atrazine as the sole N source, free ammonium was not detected, suggesting assimilation into biomass. The organism degraded atrazine anaerobically in media which contained (i) atrazine only, (ii) atrazine and glucose, and (iii) atrazine, glucose, and nitrate. To date, this is the first report of a pure bacterial isolate with the ability to cleave the s triazine ring structure of atrazine. It was also concluded that this bacterium was capable of dealkylation, dechlorination, and deamination in addition to ring cleavage. PMID- 7887610 TI - Proposals for optimization of the international phage typing system for Listeria monocytogenes: combined analysis of phage lytic spectrum and variability of typing results. AB - Combined analysis of 5,179 serial phage reactions of 20 Listeria monocytogenes propagating strains over 14 years and phage typing results from 2,659 further L. monocytogenes strains allowed us to estimate lytic spectrum specificity and the variability of the lytic reactions of 35 phages. These included the 26 phages recommended for the international method for phage typing defined in 1985 by Rocourt et al. (J. Rocourt, A. Audurier, A. L. Courtieu, J. Durst, S. Ortel, A. Schrettenbrunner, and A. G. Taylor, Zentralbl. Bakteriol. Abt. 1 Orig. A 259:489 497, 1985). The results are discussed individually for each phage. Proposals for modifying the present system are made with the aim of producing an optimal bacteriophage set for routine use. PMID- 7887611 TI - Purification and characterization of ferulate and p-coumarate decarboxylase from Bacillus pumilus. AB - Bacillus pumilus PS213 isolated from bovine ruminal fluid was able to transform ferulic acid and p-coumaric acid to 4-vinylguaiacol and 4-vinylphenol, respectively, by nonoxidative decarboxylation. The enzyme responsible for this activity has been purified and characterized. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of crude extract from a culture induced by ferulic acid or p-coumaric acid shows three bands that are not present in the crude extract of an uninduced culture, while the purified enzyme shows a single band of 23 kDa; the molecular mass calculated by size exclusion chromatography is 45 kDa. Enzyme activity is optimal at 37 degrees C and pH 5.5 and is not enhanced by any cation. Kinetic studies indicated a Km of 1.03 mM and a Vmax of 0.19 mmol.min-1/mg.liter-1 for ferulic acid and a Km of 1.38 mM and a Vmax of 0.22 mmol.min-1/mg.liter-1 for p-coumaric acid. PMID- 7887612 TI - Recovery and characterization of poly(3-hydroxybutyric acid) synthesized in Alcaligenes eutrophus and recombinant Escherichia coli. AB - We studied recovery of poly(3-hydroxybutyric acid) (PHB) from Alcaligenes eutrophus and a recombinant Escherichia coli strain harboring the A. eutrophus poly(3-hydroxyalkanoic acid) biosynthesis genes. The amount of PHB degraded to a lower-molecular-weight compound in A. eutrophus during the recovery process was significant when sodium hypochlorite was used, but the amount degraded in the recombinant E. coli strain was negligible. However, there was no difference between the two microorganisms in the patterns of molecular weight change when PHB was recovered by using dispersions of a sodium hypochlorite solution and chloroform. To understand these findings, we examined purified PHB and lyophilized cells containing PHB by using a differential scanning calorimeter, a thermogravimetric analyzer, and nuclear magnetic resonance. The results of our analysis of lyophilized whole cells containing PHB with the differential scanning calorimeter suggested that the PHB granules in the recombinant E. coli strain were crystalline, while most of the PHB in A. eutrophus was in a mobile amorphous state. The stability of the native PHB in the recombinant E. coli strain during sodium hypochlorite treatment seemed to be due to its crystalline morphology. In addition, as determined by the thermogravimetric analyzer study, lyophilized cell powder of the recombinant E. coli strain containing PHB exhibited greater thermal stability than purified PHB obtained by chloroform extraction. The PHB preparations extracted from the two microorganisms had identical polymer properties. PMID- 7887614 TI - Specificity of reductive dehalogenation of substituted ortho-chlorophenols by Desulfitobacterium dehalogenans JW/IU-DC1. AB - Resting cells of Desulfitobacterium dehalogenans JW/IU-DC1 growth with pyruvate and 3-chloro-4-hydroxyphenylacetate (3-Cl-4-OHPA) as the electron acceptor and inducer of dehalogenation reductively ortho-dehalogenate pentachlorophenol (PCP); tetrachlorophenols (TeCPs); the trichlorophenols 2,3,4-TCP, 2,3,6-TCP, and 2,4,6 TCP; the dichlorophenols 2,3-DCP, 2,4-DCP, and 2,6-DCP; 2,6-dichloro-4-R-phenols (2,6-DCl-4-RPs, where R is -H, -F, -Cl, -NO2, -CO2, or -COOCH3; 2-chloro-4-R phenols (2-Cl-4-RPs, where R is -H, -F, -Cl, -Br, -NO2, -CO2-, -CH2CO2, or COOCH3); and the bromophenols 2-BrP, 2,6-DBrP, and 2-Br-4ClP [corrected]. Monochlorophenols, the dichlorophenols 2,5-DCP, 3,4-DCP, and 3,5-DCP, the trichlorophenols 2,3,5-TCP, 2,4,5-TCP, and 3,4,5-TCP, and the fluorinated analog of 3-Cl-4-OHPA, 3-F-4-OHPA ("2-F-4-CH2CO2- P"), are not dehalogenated. A chlorine substituent in position 3 (meta), 4 (para), or 6 (second ortho) of the phenolic moiety facilitates ortho dehalogenation in position 2. Chlorine in the 5 (second meta) position has a negative effect on the dehalogenation rate or even prevents dechlorination in the 2 position. In general, 2,6-DCl-4-RPs are dechlorinated faster than the corresponding 2-Cl-4-RPs with the same substituent R in the 4 position. The highest dechlorination rate, however, was found for dechlorination of 2,3-DCP, with a maximal observed first-order rate constant of 19.4 h-1 g (dry weight) of biomass-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887613 TI - Regulation of manganese peroxidase gene transcription by hydrogen peroxide, chemical stress, and molecular oxygen. AB - The expression of manganese peroxidase (MnP) in nitrogen-limited cultures of the lignin-degrading fungus Phanerochaete chrysosporium is regulated at the level of gene transcription by H2O2 and various chemicals, including ethanol, sodium arsenite, and 2,4-dichlorophenol, as well as by Mn(II) and heat shock. Northern (RNA) blot analysis demonstrates that the addition of 1.0 mM H2O2 to 5-day-old cultures grown in the absence of Mn results in the appearance of mnp mRNA within 15 min. Higher levels of mnp mRNA are obtained with simultaneous induction by Mn and H2O2 than with H2O2 alone. Although neither MnP activity nor associated protein is detectable in H2O2-induced cultures grown in the absence of Mn, simultaneous induction with Mn and H2O2 results in a 1.6-fold increase in MnP activity compared with the MnP activity resulting from Mn induction alone. In the presence of Mn, purging of low-nitrogen cultures with 100% O2, in contrast to incubation under air, results in an increase in the accumulation of mnp mRNA and a 13-fold increase in MnP activity on day 5. However, in contrast to the effects of H2O2 and heat shock, O2 purging of Mn-deficient cultures results in negligible accumulation of mnp mRNA. PMID- 7887615 TI - Competitive metabolism of naphthalene, methylnaphthalenes, and fluorene by phenanthrene-degrading pseudomonads. AB - Polynuclear aromatic hydrocarbons (PAHs) typically exist as complex mixtures in contaminated soils, yet little is known about the biodegradation of PAHs in mixtures. We have isolated two physiologically diverse bacteria, Pseudomonas stutzeri P-16 and P. saccharophila P-15, from a creosote-contaminated soil by enrichment on phenanthrene as the sole carbon source and studied their ability to metabolize several other two- and three-ring PAHs. Naphthalene, 1 methylnaphthalene, and 2-methylnaphthalene served as growth substrates for both organisms, while fluorene was only cometabolized. We also studied the effects of these compounds on initial rates of phenanthrene uptake in binary mixtures. Lineweaver-Burk analysis of kinetic measurements was used to demonstrate competitive inhibition of phenanthrene uptake by all four compounds, suggesting that multiple PAHs are being transformed by a common enzyme pathway in whole cells. Estimates of the inhibition coefficient, Ki, are reported for each compound. The occurrence of competitive metabolic processes in physiologically diverse organisms suggests that competitive metabolism may be a common phenomenon among PAH-degrading organisms. PMID- 7887616 TI - Analysis of viral RNA persistence in seawater by reverse transcriptase-PCR. AB - It is important to determine the stability of naked viral RNA in seawater, since false-positive results can occur when reverse transcriptase-PCR (RT-PCR) is used to detect viruses if the RT-PCR amplifies free RNA instead of RNA from intact viruses. An acid guanidinium thiocyanate-phenol-chloroform method was used to extract total RNA from a filtered poliovirus cell culture suspension. The sensitivity of detection in this viral RNA study was 600 fg when RT-PCR was used. The extracted total RNA was seeded into filtered and unfiltered seawater, and the resulting preparations were incubated at 4 degrees C and at room temperature (23 +/- 1 degrees C). Our results showed that the seeded RNA was more stable in filtered seawater than in unfiltered seawater at both temperatures. The viral RNA could not be detected by the RT-PCR after 2 days of incubation in unfiltered seawater and after 28 days of incubation in filter-sterilized seawater. Therefore, because of the relatively short life of viral RNA in natural water, the detection of virus in environmental samples by the RT-PCR was mainly due to the presence of well-protected viral particles and not due to the presence of naked viral RNA. PMID- 7887617 TI - Active site analysis and stabilization of sarcosine oxidase by the substitution of cysteine residues. AB - Two cysteine residues (C-265 and C-318) in the putative hydrophilic regions of sarcosine oxidase were substituted by using site-directed mutagenesis. Since the mutant with the C-to-S mutation at position 318 (C318S) lost the enzyme activity, C-318 (conserved among sarcosine oxidases) is most likely a part of the active site. C265S, C265A, C265D, and C265R showed nearly the same enzymatic properties as those of the wild type. However, they were much more stable than the wild type in the presence of inhibitors that modified the thiol group. Moreover, they were extremely stable throughout the cultivation of the recombinant strains or even in cell extracts. PMID- 7887618 TI - Genotypic characterization of Mycobacterium avium strains recovered from animals and their comparison to human strains. AB - Mycobacterium avium was recovered from 21 birds and 10 pigs. Bird isolates carried IS901 and a few copies of IS1245 and appeared highly related by pulsed field gel electrophoresis. Pig isolates showed features previously described in human isolates: a lack of IS901, a high copy number of IS1245, and marked polymorphism by pulsed-field gel electrophoresis. PMID- 7887619 TI - Occurrence of high-level aminoglycoside resistance in environmental isolates of enterococci. AB - High-level resistance to aminoglycosides was observed in environmental isolates of enterococci. Various aquatic habitats, including agricultural runoff, creeks, rivers, wastewater, and wells, were analyzed. Strains of Enterococcus faecalis, E. faecium, E. gallinarum, and other Enterococcus spp. demonstrated multiple antibiotic resistance patterns to aminoglycosides. PMID- 7887620 TI - Discrimination of species in the genus Listeria by Fourier transform infrared spectroscopy and canonical variate analysis. AB - Infrared spectra of type cultures of the six recognized species of the genus Listeria and of Listeria grayi subsp. murrayi were recorded. By use of a library of 59 spectra, comprising at least six replicates of each type, discrimination by canonical variate analysis of the spectral amplitudes allowed all of the spectra to be correctly classified. PMID- 7887621 TI - Growth and survival of Escherichia coli O157:H7 under acidic conditions. AB - The effect of pH reduction with acetic (pH 5.2), citric (pH 4.0), lactic (pH 4.7), malic (pH 4.0), mandelic (pH 5.0), or tartaric (pH 4.1) acid on growth and survival of Escherichia coli O157:H7 in tryptic soy broth with 0.6% yeast extract held at 25, 10, or 4 degrees C for 56 days was determined. Triplicate flasks were prepared for each acid treatment at each temperature. At 25 degrees C, populations increased 2 to 4 log10 CFU/ml in all treatments except that with mandelic acid, whereas no growth occurred at 10 or 4 degrees C in any treatments except the control. However, at all sampling times, higher (P < 0.05) populations were recovered from treatments held at 4 degrees C than from those held at 10 degrees C. At 10 degrees C, E. coli O157:H7 was inactivated at higher rates in citric, malic, and mandelic acid treatments than in the other treatments. At the pH values tested, the presence of the organic acids enhanced survival of the pathogen at 4 degrees C compared with the unacidified control. E. coli O157:H7 has the ability to survive in acidic conditions (pH, > or = 4.0) for up to 56 days, but survival is affected by type of acidulant and temperature. PMID- 7887622 TI - Detection of Escherichia coli O157:H7 in meat by an enzyme-linked immunosorbent assay, EHEC-Tek. AB - Investigation of the specificity of an enzyme-linked immunosorbent assay (ELISA) for detection of Escherichia coli O157:H7 in raw meats (EHEC-Tek; Organon Teknika Corp.) revealed that the target antigens of the detection reagent, monoclonal antibody 4E8C12, were present in numerous serotypes of E. coli and that their ELISA reactivity was influenced by bile salts, acriflavine, and heat. The specificity of the ELISA was improved by a modified test protocol incorporating immunocapture. PMID- 7887623 TI - PCR and gene probe identification of botulinum neurotoxin A-, B-, E-, F-, and G producing Clostridium spp. and evaluation in food samples. AB - A degenerate primer pair was selected to amplify specifically a 260-bp DNA fragment from Clostridium botulinum types A, B, E, F, and G, and five individual probes allowed identification of each toxinotype by hybridization of the PCR products. The 72 strains of different Clostridium species tested and 11 other bacterial species commonly found in food samples gave an amplification product. This assay was able to detect 1 C. botulinum type A or B and 10 C. botulinum type E strains per reaction. With 184 artificially contaminated food samples, after an 18-h enrichment step, the sensitivity was 10 bacteria per g of sample and the correlation with the mouse bioassay reached 95.6%. PMID- 7887624 TI - Inhibition enzyme-linked immunosorbent assay for detection of Pseudomonas fluorescens on meat surfaces. AB - An inhibition enzyme-linked immunosorbent assay was developed for Pseudomonas fluorescens enumeration of meat surfaces. The assay detected contamination levels as low as 3 x 10(5) bacteria per ml and could be completed within 4 h. It could be used as a framework for a test system for quantifying P. fluorescens spoilage in meat products. PMID- 7887625 TI - Sequence variability in homologs of the aflatoxin pathway gene aflR distinguishes species in Aspergillus section Flavi. AB - The Aspergillus parasiticus aflR gene, a gene that may be involved in the regulation of aflatoxin biosynthesis, encodes a putative zinc finger DNA-binding protein. PCR and sequencing were used to examine the presence of aflR homologs in other members of Aspergillus Section Flavi. The predicted amino acid sequences indicated that the same zinc finger domain, CTSCASSKVRCTKEKPACARCIERGLAC, was present in all of the Aspergillus sojae, Aspergillus flavus, and Aspergillus parasiticus isolates examined and in some of the Aspergillus oryzae isolates examined. Unique base substitutions and a specific base deletion were found in the 5' untranslated and zinc finger region; these differences provided distinct fingerprints. A. oryzae and A. flavus had the T-G-A-A-X-C fingerprint, whereas A. parasiticus and A sojae had the C-C-C-C-C-T fingerprint at the corresponding positions. Specific nucleotides at positions -90 (C or T) and -132 (G or A) further distinguished A. flavus from A. oryzae and A. parasiticus from A. sojae, respectively. A sojae ATCC 9362, which was previously designated A. oryzae NRRL 1988, was determined to be a A. sojae strain on the basis of the presence of the characteristic fingerprint, A-C-C-C-C-C-C-T. The DNAs of other members of Aspergillus Section Flavi, such as Aspergillus nomius and Aspergillus tamarii, and some isolates of A. oryzae appeared to exhibit low levels of similarity to the A. parasiticus aflR gene since low amounts of PCR products or no PCR products were obtained when DNAs from these strains were used. PMID- 7887626 TI - A new Agrobacterium strain isolated from aerial tumors on Ficus benjamina L. AB - Crown gall tumors, collected from branches of 1-year-old weeping fig (Ficus benjamina L.) trees, yielded both tumorigenic and nonpathogenic agrobacteria. On the basis of classical diagnostic tests, the nonpathogenic strains were identified as Agrobacterium tumefaciens, whereas the tumorigenic strains could not be assigned to any of the known terrestrial Agrobacterium spp. The tumorigenic strains also differed from other members of the genus by producing more acid from mannitol. According to cluster analysis of carbon substrate oxidation (GN Microplate; Biolog, Inc.) and fatty acid content, the tumorigenic fig strains were distinct from strains of A. tumefaciens, Agrobacterium rhizogenes, Agrobacterium vitis, and Agrobacterium rubi. Furthermore, they had unusual opine metabolism, inducing tumors that synthesized nopaline and three recently discovered opines: chrysopine (d-lactone of N-1-deoxy-D-fructosyl-L glutamine, and N-1-deoxy-D-fructosyl-L-glutamine, and N-1-deoxy-D-fructosyl-5-oxo L-proline. The nonpathogenic A. tumefaciens strains present in the same tumors were unable to degrade any of the opines tested. The phylogenetic position of the tumorigenic fig strain AF3.10 was inferred from comparing its rrs (i.e., 16S rRNA gene) sequence with those from the type strains of Agrobacterium and Rhizobium species. The analysis showed that strain AF3.10 clustered with A. tumefaciens and A. rubi but not with A. vitis and was far removed from A. rhizogenes. However, the sequence was significantly different from those of A. tumefaciens and A. rubi to suggest that the tumorigenic fig strain may be a new Agrobacterium species that is as different from A. tumefaciens and A. rubi as these two species are from one another. PMID- 7887628 TI - Genetic analysis of fumonisin production and virulence of Gibberella fujikuroi mating population A (Fusarium moniliforme) on maize (Zea mays) seedlings. AB - The phytopathogenic fungus Gibberella fujikuroi mating population A (anamorph, Fusarium moniliforme) produces fumonisins, which are toxic to a wide range of plant and animal species. Previous studies of field strains have identified a genetic locus, designated fum1, that can determine whether fumonisins are produced. To test the relationship between fumonisin production and virulence on maize seedlings, a cross between a fum1+ field strain that had a high degree of virulence and a fum1- field strain that had a low degree of virulence was made, and ascospore progeny were scored for these traits. Although a range of virulence levels was recovered among the progeny, high levels of virulence were associated with production of fumonisins, and highly virulent, fumonisin-nonproducing progeny were not obtained. A survey of field strains did identify a rare fumonisin-nonproducing strain that was quite high in virulence. Also, the addition of purified fumonisin B1 to virulence assays did not replicate all of the seedling blight symptoms obtained with autoclaved culture material containing fumonisin. These results support the hypothesis that fumonisin plays a role in virulence but also indicate that fumonisin production is not necessary or sufficient for virulence on maize seedlings. PMID- 7887627 TI - Effect of inducible thrB expression on amino acid production in Corynebacterium lactofermentum ATCC 21799. AB - Amplification of the operon homdr-thrB encoding a feedback-insensitive homoserine dehydrogenase and a wild-type homoserine kinase in a Corynebacterium lactofermentum lysine-producing strain resulted in both homoserine and threonine accumulation, with some residual lysine production. A plasmid enabling separate transcriptional control of each gene was constructed to determine the effect of various enzyme activity ratios on metabolite accumulation. By increasing the activity of homoserine kinase relative to homoserine dehydrogenase activity, homoserine accumulation in the medium was essentially eliminated and the final threonine titer was increased by about 120%. Furthermore, a fortuitous result of the cloning strategy was an unexplained increase in homoserine dehydrogenase activity. This resulted in a further decrease in lysine production along with a concomitant increase in threonine accumulation. PMID- 7887629 TI - Effects of electron donor and acceptor conditions on reductive dehalogenation of tetrachloromethane by Shewanella putrefaciens 200. AB - Shewanella putrefaciens 200 is a nonfermentative bacterium that is capable of dehalogenating tetrachloromethane to chloroform and other, unidentified products under anaerobic conditions. Since S. putrefaciens 200 can respire anaerobically by using a variety of terminal electron acceptors, including NO3-, NO2-, and Fe(III), it provides a unique opportunity to study the competitive effects of different electron acceptors on dehalogenation in a single organism. The results of batch studies showed that dehalogenation of CT by S. putrefaciens 200 was inhibited by O2, 10 mM NO3-, and 3 mM NO2-, but not by 15 mM Fe(III), 15 mM fumarate, or 15 mM trimethylamine oxide. Using measured O2, Fe(III), NO2-, and NO3- reduction rates, we developed a speculative model of electron transport to explain inhibition patterns on the basis of (i) the kinetics of electron transfer at branch points in the electron transport chain, and (ii) possible direct inhibition by nitrogen oxides. In additional experiments in which we used 20 mM lactate, 20 mM glucose, 20 mM glycerol, 20 mM pyruvate, or 20 mM formate as the electron donor, dehalogenation rates were independent of the electron donor used. The results of other experiments suggested that sufficient quantities of endogenous substrates were present to support transformation of tetrachloromethane even in the absence of an exogenous electron donor. Our results should be significant for evaluating (i) the bioremediation potential at sites contaminated with both halogenated organic compounds and nitrogen oxides, and (ii) the bioremediation potential of iron-reducing bacteria at contaminated locations containing significant amounts of iron-bearing minerals. PMID- 7887630 TI - Persistence of inoculated hepatitis A virus in mixed human and animal wastes. AB - The persistence of hepatitis A virus (HAV) was determined both in mixtures of septic tank effluent (STE) with dairy cattle manure slurry (DCMS) and in mixtures of STE with swine manure slurry (SMS). HAV was consistently inactivated more rapidly in the two types of mixed wastes than in STE alone or in the control Dulbecco's phosphate-buffered saline (PBS). At 5 degrees C, the D values (time, in days, for a 90% reduction of virus titer) were 34.6 for the mixed STE and DCMS, 48.5 for the mixed STE and SMS, 58.5 for STE, and 217.4 for the Dulbecco's PBS control. At 22 degrees C, the D values were 23.0, 17.1, 35.1, and 90.1 for the four suspension media, respectively. A comparison of HAV inactivation in mixed wastes subjected to different treatments at the same pH and temperatures showed that the virus inactivation in the mixed wastes was related, at least in part, to microbial activity. In mixed STE and DCMS, the D values at 25 degrees C were 8.3 for raw mixed wastes, 15.1 for autoclaved mixed wastes, and 9.6 for bacterium-free filtrate of raw mixed wastes; D values at 37 degrees C were 6.8, 10.1, and 7.0 for these three suspension media, respectively. In mixed STE and SMS, the D values at 25 degrees C were 8.1 for raw mixed wastes, 14.3 for autoclaved mixed wastes, and 9.1 for bacterium-free filtrate of raw mixed wastes; the D values at 37 degrees C were 6.8, 9.4, and 6.9 for the three suspensions, respectively. PMID- 7887631 TI - In situ inactivation of animal viruses and a coliphage in nonaerated liquid and semiliquid animal wastes. AB - The persistence of five animal viruses, representing picorna-, rota-, parvo-, adeno-, and herpesviruses, and the coliphage f2 was determined in the field by exposing the viruses to different animal wastes and by adopting an established filter sandwich technique. This technique allows us to copy the natural state of viruses in the environment, where adsorption onto or incorporation into suspended solids may prolong virus survival. Using filter sandwiches either equipped with porous (15 nm in diameter) or poreless polycarbonate (PC) membranes, it was possible to differentiate between overall virus inactivation and the effect of virucidal agents that act through poreless PC membranes. Depending on ambient temperature, pH, and type of animal waste, values for time, in days, required for a 90% reduction of virus titer varied widely, ranging from less than 1 week for herpesvirus to more than 6 months for rotavirus. Virus inactivation progressed substantially faster in liquid cattle manure, a mixture of urine and water (pH > 8.0), than in semiliquid wastes that consisted of mixtures of feces, urine, water, and bedding materials (pH < 8.0). Hitherto unidentified virucidal agents that permeate poreless PC membranes contributed substantially to the overall inactivation. On the other hand, substances that protect rotavirus and possibly other viruses from inactivation may be present in animal wastes. Together, the study showed that viruses contained in manure may persist for prolonged periods of time if stored under nonaerated conditions. At times of land application, this may lead to environmental contamination with pathogens. PMID- 7887632 TI - Specific oligonucleotide primers for detection of lecithinase-positive Bacillus spp. by PCR. AB - An assay based on the PCR has been developed to facilitate detection and identification of Bacillus cereus in foods. Three primers for the PCR have been designed within the sequence for cereolysin AB, a cytolytic determinant that encodes lecithin-hydrolyzing and hemolytic activities of B. cereus. With the PCR and hybridization, the specificity of the primers was tested with 39 isolates of the B. cereus group, with 17 other Bacillus spp., and with 21 non-Bacillus strains. Results demonstrate a high specificity of the three oligonucleotides for isolates of the B. cereus group. With a combined PCR-hybridization assay, the detection limit for B. cereus in artificially contaminated milk was 1 CFU/ml of milk. PMID- 7887633 TI - [Protease inhibitors as anticancer chemotherapy--experimental and clinical studies]. AB - A synthetic protease inhibitor FOY-305 (Foypan) not only inhibited the skin tumorigenesis in mice but also suppressed the growth of autochthonous solid tumor in mice. Furthermore, administration of FOY-305 inhibited the metastasis of Lewis lung carcinoma and colon adenocarcinoma to the lung in mice, experimentally and spontaneously. Clinically, FOY-305 prevented both recurrence and metastasis in the patients who had received many anticancer drugs. In 2 terminal secondary cases, tumor remission and elongation of survival time were observed. Above results suggest a possibility for applying a new type chemotherapy using protease inhibitors. PMID- 7887634 TI - [Progress of chemotherapy in adult acute leukemia]. AB - Due to the advance of chemotherapy and bone marrow transplantation (BMT), adult acute leukemia has become a curable disease. Since in BMT a good prognosis is obtained in chemotherapy-induced remission cases, chemotherapy plays a major role for the cure of this disease. In acute myeloid leukemia, the JALSG AML 89 study resulted in a 77% complete remission (CR) rate in 326 adults, 38% of whom had a 4.5-year diseases-free survival (DFS) rate in CR cases. However, the results of acute lymphoblastic leukemia in the JALSG ALL 87 study were not satisfactory; 84% CR in 116 adults and only 24% 6-year DFS. PMID- 7887635 TI - [Recent progress in the chemotherapy of malignant lymphoma]. AB - Recent progress in the chemotherapy of malignant lymphoma is described from the viewpoint of survival advantage. Malignant lymphoma is classified into the following five major categories: aggressive lymphoma, indolent B-lymphoma, Hodgkin's disease, T-lymphoblastic lymphoma and adult T-cell leukemia-lymphoma (ATL). In aggressive lymphoma of advanced stages, recent multicenter phase III studies revealed that first-generation CHOP therapy remains the best available treatment. By multivariate analysis on prognostic factors of non-ATL lymphoma patients who were treated by the second generation LSG 4 protocol, CRP and total number of involved lesions were found to be significantly unfavorable factors. In non-ATL lymphoma, mainly B-lymphoma, three risk groups (low, intermediate and high) were identified. Similarly, the International Non-Hodgkin's Lymphoma Prognostic Factors Project proposed a new predictive model for survival of aggressive lymphoma patients. Such predictive models would be very useful in the design of future chemotherapy trials for aggressive lymphoma. In advanced-stage Hodgkin's disease, about two-thirds of patients are expected to be long-term survivors, thanks to state-of-the-art chemotherapy. A recent phase III study conducted by CALGB disclosed that MOPP/ABVD and ABVD are superior to MOPP. In ATL and indolent B-lymphoma, no state-of-the-art chemotherapy has been established. In order to improve the prognosis of both diseases, innovative treatment strategies should be pursued. PMID- 7887637 TI - [Recent progress in chemotherapy for advanced lung cancer]. AB - Recent progress in chemotherapy for advanced nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC) maybe summarized as follows. 1) In seven randomized trials of combination chemotherapy compared with best supportive care in stage IV NSCLC, meta-analysis of indicated that combination chemotherapy modestly improves survival of patients with advanced NSCLC. 2) Cisplatin-based combination chemotherapy followed by chest irradiation improves outcomes of patients with stage III unresectable NSCLC as compared with radiation therapy alone. 3) Meta-analysis has shown that survival is prolonged when radiotherapy is used in combination with chemotherapy in the treatment of limited-stage SCLC. 4) Randomized trials evaluating alternating chemotherapy could not demonstrate the survival benefit in the treatment of extensive-stage (ES) SCLC. 5) The approach to increasing dose intensity has been attempted in the treatment of ES-SCLC. The most common approach is weekly chemotherapy. Results of pilot studies have suggest that this approach prolong survival of patients with ES-SCLC. 6) Recently, several new drugs active against NSCLC and SCLC, including CPT-11, taxol, axotere, vinorelbine and gemcitabine, have been developed. In conclusion, despite these advances of treatment, the cure rate remains quite low in lung cancer. Further investigations are needed to improve the treatment results for patients with this disease. PMID- 7887636 TI - [Recent advances in chemotherapy for advanced gastric cancer: from the standpoint of survival advantages]. AB - Recently, there have been many reports indicating higher response rates in combination chemotherapies for advanced gastric cancer. Since 1990, several randomized controlled trials (RCT) have been reported, which showed evidences of survival impacts in such cases. Patients treated with chemotherapy obtained significant survival advantages over those with best supportive care in three RCTs. The RCT from EORTC also resulted in more significant survival prolongation in FAMTX than in FAM, and FAMTX should be a reference arm for new regimens. Some RCTs are now under way to establish a standard therapy for advanced gastric cancer. From the analysis of long-term results of Japanese studies, 3% of entry cases survived longer than 5 years with no evidence of disease by chemotherapy. Chemotherapy for gastric cancer should be evaluated with survival advantages or rate of long-term survivors in future studies. PMID- 7887638 TI - [Smooth induction and stable maintenance of hypertensive state for clinical response in angiotensin II-induced hypertension chemotherapy]. AB - In angiotensin II (A II)-induced hypertension chemotherapy (IHC), the role of the level of hypertension induced by A II and pattern of maintenance of the state was investigated in 5,840 IHC records of 264 patients. The pattern of IHC records of each patient was evaluated according to the range of the mean elevated blood pressure (MBPe) and induced hypertension point (IHTP). The MBPe of each record was calculated from 5-7 randomly selected values. The range of MBPe from each record was estimated, while discarding the max and min values. IHTP was classified into three categories as follows: 1:160 > MBPe > or = 140, 2: MBPe > 160 and 140 > MBPe > or = 130; and 3: 130 > MBPe. The most frequent category of all records was determined as the IHTP of each patient. One point was added to IHTP, when the fluctuation range of MBPe was more than 10 mmHg, and when the other categories were mixed more than 25% among all records. The MBPe of CR + PR group were significantly higher than in the other non-response group. IHTP was also better in responders. Many patients aged below 40 responded poorly to A II, and the level of MBPe was significantly lower than that of patients above 40. It may be essential to induce the hypertensive level and maintain a stable state during IHC for enhancement of clinical effects. Symptoms accompanied during IHC such as chest oppressive sense, dull head pain, and abdominal discomfort were observed in half the patients, although the IHC procedure almost never had to be discontinued. PMID- 7887639 TI - [Clinical effects of carmofur (Mifurol) on advanced and recurrent breast cancer in a cooperative study. Research association for re-evaluation of direct effects of Mifurol on breast cancer]. AB - The direct effect and safety of carmofur (Mifurol) in cases of advanced and recurrent breast cancer were evaluated as a cooperative study at twenty-two facilities nationwide. Carmofur 12 mg/kg/day within the maximum daily dose of 600 mg was administered orally for eight weeks or longer. Of 42 patients registered for the study, 38 met the eligibility criterial (qualified patients), of whom 31 completed all tests for evaluation (completely qualified patients). The response rates were 18.4% with the qualified patients (PR, 7; Long NC, 3; NC, 11; PD, 12; NE, 5; ie, 7/38), and 22.6% with the completely qualified patients (PR, 7; Long NC, 2; NC, 10; PD, 12; ie, 7/31). The interval before the onset of PR after administration of carmofur was started was a minimum 29 days, a maximum 190 days and a median 82 days. Side effects were observed in eighteen patients (42.9%). Frequent micturition, loss of appetite, dizziness or feverish feeling were major symptoms, but none were serious. PMID- 7887640 TI - [A dose-comparative study on TAP-144-SR, an LH-RH agonist depot formulation, in premenopausal patients with advanced or recurrent breast cancer. TAP-144-SR Breast Cancer Study Group]. AB - A comparative phase II study was performed with different doses of TAP-144-SR in ER-positive or ER-unknown premenopausal patients with advanced or recurrent breast cancer. One hundred and six patients were randomly allocated to either 3.75 mg or 7.5 mg treatment by a centralized telephone registration system. TAP 144-SR was administered sc at 4-week intervals for 12 weeks (a total of 3 injections). Ninety-five cases were evaluated with the response rate of 30.4% (14/46) in the 3.75 mg group and 24.5% (12/49) in the 7.5 mg group, respectively. Serum estradiol was decreased to postmenopausal level (< 30 pg/ml) within 3-4 weeks after the first dose in the both dose groups, and this suppression was maintained throughout the treatment period. The adverse reactions most frequently observed were climacteric disturbances like hot flashes which was likely to be due to the hypoestrogen status. In conclusion, there was no significant difference between both dose groups in terms of response rates, adverse effects, and hormonal suppression. Therefore, the lower dose is recommended for the further study. PMID- 7887641 TI - [Long-term clinical study on TAP-144-SR, an LH-RH agonist depot formulation, in premenopausal patients with advanced or recurrent breast cancer. TAP-144-SR Breast Cancer Study Group]. AB - Efficacy and safety of long-term treatment with an LH-RH agonist, TAP-144-SR were studied in premenopausal patients with advanced or recurrent breast cancer. The drug was given sc every 4 week at the dose of 3.75 or 7.5mg. The best objective response rates were 37.0% (17/46) in 3.75mg group, 30.6% (15/49) in 7.5mg group, respectively. The median duration of 12 PR patients in 3.75mg group was 280 (range: 84-830+) days. Serum estradiol level was maintained at < 30pg/ml in most patients given 3.75mg or 7.5mg as scheduled. There was no adverse reactions specific to the longterm administration subsequent to the foregoing 12-week administration study in both dose groups. In conclusion, TAP-144-SR is expected to be one of the first line therapies for patients with premenopausal breast cancer. PMID- 7887642 TI - [Study of PyNPase activity in patients with gastric cancer--the association with preoperative IAP values]. AB - 5'-DFUR manifests its antitumor activity after being converted to 5-FU by pyrimidine nucleoside phosphorylase (PyNPase), an enzyme having high activity in tumor tissue. We surgically removed tissue samples weighing at least 1 g from 28 patients with gastric cancer and measured the PyNPase activity. The tissue samples were taken from gastric carcinomas, normal gastric tissue, metastasis positive lymph nodes, metastasis-negative lymph nodes, small intestine, spleen, and other organs. The PyNPase activity was higher in gastric carcinomas than in normal gastric tissue. Similarly, metastasis-positive lymph nodes showed higher PyNPase activity than in metastasis-negative lymph nodes. PyNPase activity in the spleen was approximately equivalent to that in gastric carcinomas. Correlations were assessed between the PyNPase activity of gastric carcinomas and their tissue type. Stage and nutritional status, but there was no correlation with PyNPase activity for any of the variables assessed. The relationship between the PyNPase activity of gastric carcinomas and serum IAP concentration measured within one week before operation was similarly assessed. Mean PyNPase activity in the group of 14 patients with low serum IAP concentrations (< 550 micrograms/ml) was 102.8, while that in 11 patients with high serum IAP concentrations (> or = 550 micrograms/ml) was 145.7. Although this difference was not significant, there tended to be a positive correlation between PyNPase activity and serum IAP concentration (r = 0.74). PyNPase activity in splenic tissue was significantly higher in group of 10 patients with low IAP activity (104.7) (p = 0.020). These results indicated that patients with high serum IAP concentrations, generally associated with a poor prognosis, showed a high PyNPase activity in tumor tissue and splenic tissue. PyNPase activity, including its involvement in the immune response, was thus suggested to be somehow related to prognosis. PMID- 7887643 TI - [Combination chemotherapy with FP versus FEP in patients with advanced gastric cancer. Research group of gastric cancer chemotherapy]. AB - Forty-eight patients with unresectable gastric cancer were enrolled for a randomized trial of FP (n = 24) vs FEP (n = 24) combination chemotherapy with respect to their effects on survival period. Of these, excluding 7 patients, 21 in FP group were treated with 400 mg/m2 UFT po daily and 50 mg/m2 CDDP i.v. on days 1 and 8 every 4 weeks, and 20 in FEP group were treated with 400 mg/m2 UFT po daily, 50 mg/m2 etoposide iv and 50 mg/m2 CDDP i.v. on days 1 and 8 every 4 weeks. In FP group, 10 PR in primary lesions were observed with an overall response rate of 52.4%. In FEP group, 5 PR in primary lesions were observed with an overall response rate of 35.0%. Toxicities over Grade 3 were anorexia (35%), vomiting (25%), and leukopenia (12%), which were manageable. The 50% survival time in FP and FEP group was 233 and 176 days, respectively. Because of the high response rate and prolongation of the survival period, combination chemotherapy with FP seemed to be useful for the treatment of patients with advanced gastric cancer. PMID- 7887644 TI - [A randomized early phase II study of l-leucovorin and 5-fluorouracil in gastric cancer. l-Leucovorin and 5-FU Study Group]. AB - A randomized early phase II study using l-leucovorin (l-LV) and 5-fluorouracil (5 FU) in gastric cancer was conducted. The administration schedules: Arm A was 250 mg/m2 of l-LV and 600 mg/m2 of 5-FU weekly, arm B was 100 mg/m2 of l-LV and 370 mg/m2 of 5-FU for 5 consecutive days, and arm C was 10 mg/m2 of l-LV and 370 mg/m2 of 5-FU for 5 consecutive days. PR was obtained in 10/28 (35.7%) of arm A, 7/28 (25.0%) of arm B and 0/17 (0%) of arm C, in complete cases. In eligible cases, 30.3%, 21.9% and 0%, respectively. Because there was no responder in arm C, the entry to arm C was stopped by controller at the point where 17 patients were treated with arm C. Median survival time was 9.6 months in arm A, 8.0 months in arm B and 5.9 months in arm C. Major toxicities were stomatitis, diarrhea and neutropenia. Stomatitis was seen more in arm B and C than in arm A. These data suggest that the high dose of l-LV and 5-FU seems to be a very promising combination, but there was no responder using low-dose l-LV schedule against gastric cancer. We thus selected arm A for the next late phase II study against gastric cancer. PMID- 7887645 TI - [Concurrent chemoradiotherapy followed by surgery for advanced stage III non small cell lung cancer (NSCLC)]. AB - Forty-two patients with stage IIIA (bronchoscopically T3 and/or bulky N2) and stage IIIB NSCLC were treated with concurrent chemoradiotherapy (CRT). Treatment consisted of CDDP, 20 mg/m2 and etoposide, 40 mg/m2 by continuous infusion (day 1 5) of weeks 1 and 5 simultaneously with chest radiotherapy (RT), 50 Gy, 2 Gy/Fx, 5 Fx/week. Surgery was attempted 3-5 weeks after RT in pts clinically downstaged. Between 10/90 and 12/92, 43 previously untreated pts were enrolled and 42 were eligible. Pts characteristics were: male/female = 37/5; mean age, 61 yrs (range, 31-74 yrs); stage IIIA/IIIB = 10/32; 15 adenocarcinoma, 24 squamous cell, 2 large cell, 1 unclassified; PS 0/1/2 = 11/24/7. Excluding 1 ineligible pts, 42 pts were evaluated for CRT response. The response rate was 81% (1 CR, 33 PR, 5 NC, 1 PD, 2 NE). Clinical downstaging was achieved in 20 pts (48%). Twenty-one pts (50%) received surgery and 19 of them were completely resected. In 7 resection specimens, no tumor was observed. Toxicity of CRT was well tolerable (Grade 4 leukopenia, 15%; Grade 2-3 esophagitis, 15%). We conclude that this intensive combined modality therapy is acceptable and appears to increase the response rate as well as resectability. Prospective randomized studies should be conducted for further evaluation of this treatment modality. PMID- 7887646 TI - [Clinical effects of FUT-187 in reflux esophagitis after gastrectomy]. AB - FUT-187 was orally administered to 38 patients with postgastrectomy reflux esophagitis for 4 weeks. The drug reduced the chief subjective symptoms of reflux esophagitis, such as heartburn, chest pain, precordial pain, and dysphagia for solids in 78.1% of patients. Redness, edema and erosion were also reduced in 53.3% of patients as determined endoscopically. Overall, FUT-187 exhibited an excellent therapeutic effect on the reflux esophagitis which was refractory to conventional treatments. PMID- 7887647 TI - [Two cases of adult T-cell leukemia . lymphoma (ATL) with long-term remission by chronic daily administration of low-dose etoposide]. AB - We tried long-term oral administration of low-dose etoposide (LDE) for seven patients with adult T-cell leukemia . lymphoma (ATL) at Asahikawa Red Cross Hospital in 1988. Two long-term survivors are presented. Case 1: A 53-year-old man was diagnosed as acute ATL in 1987. Because VEPA therapy was not effective, LDE (50 mg/day) therapy was started. Five months after entering CR, a lymphoma recurrence in the skin was observed. Retreatment with LDE and radiation therapy was effective, but he died of reprogression of ATL three years and seven months following initial diagnosis. Case 2: A 43-year-old woman was diagnosed as acute ATL in 1989. With LDE (50 mg/day) therapy for 40 days, she entered CR. The lymphoma recurred in the central nervous system (CNS) and skin in 1992. After radiation of CNS and LDE therapy, she showed CR again. She is alive now over five years and eight months after diagnosis. PMID- 7887648 TI - [Dynamic change of serum UFT concentration in a patient with tongue cancer complicating chronic renal failure]. AB - To evaluate the effect of UFT as a postoperative adjuvant chemotherapeutic agent for a patient with tongue cancer complicating chronic renal failure, we measured a dynamic change of serum tegafur (FT), 5-FU and uracil concentrations in hemodialysis. When the patient administered 200 mg of UFT orally one hr before hemodialysis, serum 5 FU concentration was 0.051 micrograms/ml at the beginning of hemodialysis, then rapidly increased to 0.396 micrograms/ml at maximum one hr later and thereafter decreased to the initial level after 4 hrs, the end of hemodialysis. Even after hemodialysis, however, 5-FU maintained the effective serum concentration. On the other hand, serum FT and uracil levels showed a slight change during hemodialysis. The maximum concentrations of FT and uracil were 3.154 micrograms/ml and 0.540 micrograms/ml respectively, after 3 hrs of dialysis. We next measured serum levels of 5-FU, FT and uracil during two days without hemodialysis treatment. Although their serum levels were increased after UFT administration, those were decreased to the initial level on the next day, indicating no drug accumulation. These results suggest that UFT was safe and useful as a postoperative adjuvant chemotherapeutic agent in a cancer patient being performed hemodialysis. PMID- 7887649 TI - [A case of bilateral multiple lung metastases from breast cancer successfully treated with carboplatin]. AB - A 57-year-old female was admitted for right breast tumor. Modified radical mastectomy (Kodama method) was carried out. A prophylactic postoperative radiation was undertaken because of large tumor (T4b) and histologic metastasis to a Rotter's lymph node. At the end of irradiation, bilateral lung metastases were found on chest CT gram. The combination endocrine chemotherapy using MPA 600 mg and UFT 3 capsules p.o. daily and ADM 10 or 20 mg i.v. every two weeks was performed on an outpatient basis. As the lung metastases were increased four months later, carboplatin 150 mg i.v. was replaced with ADM. Four months later, the metastases almost disappeared on CT gram. These results suggested the possibility of one of the therapeutic options for metastatic breast cancer. PMID- 7887650 TI - [A case of multiple liver metastasis from remnant gastric cancer responding to leucovorin.5-FU+UFT therapy]. AB - We report a case of a 67-year-old male patient who experienced multiple liver metastasis 6 months after undergoing an operation for remnant gastric cancer. The histological classification of the cancer in gastric remnant was poorly differentiated adenocarcinoma. The patient was treated with a low dose of LV.5-FU once a week and oral UFT as an outpatient. As a result, after 3 months of the treatment, CT showed that multiple liver lesions almost disappeared, a condition that lasted about 3 years without relapse. Toxic effects due to this treatment were temporary slight liver disfunction, mild anorexia and stomatitis. This case indicates that the regimen of LV.5-FU+UFT may be effective for multiple liver metastasis from postoperative remnant gastric cancer, enabling the patient to maintain an excellent QOL (quality of life). PMID- 7887651 TI - [Pt levels following the infusion of daily low-dose cisplatin]. PMID- 7887652 TI - [Cross resistance of a new platinum analogue, ACT-078, to CDDP and CBDCA]. PMID- 7887653 TI - [Postoperative prognostic factors for carcinoma of the thoracic esophagus]. AB - To evaluate significant postoperative prognostic factors for esophageal carcinoma, clinicopathological findings and several markers for biological malignant potential were studied, including cell nuclear DNA contents, EGF receptor, p53 protein, MMP-2, Ki-67 positive cell rate, and tumors infiltrating Leu 7 cells. The subjects of this study were 96 patients with thoracic esophageal carcinoma, who underwent radical surgery with extended lymphadenectomy. In the pathological findings, the postoperative survival rate significantly correlated with depth of invasion (pT1(-2) vs. pT3, p = 0.003), lymph node involvement (pNo vs. pN1, p = 0.0002), vascular invasion (-vs. +, p = 0.0003), stage (pSt. 1-2A vs. 3, p = 0.0018), and the number of node involvements (1-3 vs. more than 4, p = 0.025). Analyzing the markers for the malignancy, a significant difference in postoperative mortality due to the relapse was recognized with p value of 0.0009 between Ki-67 positive (under 1%) and Ki-67 negative (over 1%) tumor. Ki-67 positive tumor significantly correlated with the mortality in both cases with pNo (p = 0.024) and pN1 (p = 0.020). Low-grade tumor infiltrating Leu 7 cells significantly correlated with the mortality (Grade 1+ vs. 2+, p = 0.013; Grade 1+ vs. 3+, p = 0.008). These results suggest that Ki-67 study is a useful prognostic factor after radical surgery for thoracic esophageal carcinoma. PMID- 7887654 TI - A vaginal prosthetic device as an aid in treating ulcerative lichen planus of the mucous membrane. Successful combination therapy with a corticosteroid-bioadhesive compound and iontophoresis. PMID- 7887655 TI - Candida krusei abdominal wall abscess presenting as ecchymosis. Diagnosis with ultrasound. PMID- 7887656 TI - Preoperative characterization of pigmented skin lesions by epiluminescence microscopy and high-frequency ultrasound. AB - BACKGROUND AND DESIGN: Previous studies have referred to the value of epiluminescence microscopy in the differential diagnosis of pigmented skin lesions and to the possibility of preoperative tumor thickness measurement in malignant melanoma by high-frequency ultrasound. Both noninvasive methods have been combined in this study. The question of improved diagnostic accuracy was discussed. Previously proposed epiluminescence microscopic characteristics of 508 melanocytic lesions and sonographic characteristics of 792 skin tumors were investigated for their sensitivity and specificity. The tumor thickness of 108 malignant melanomas was measured sonographically. RESULTS: Black dots, irregular pigment network, and grayish-blue areas have been shown to be the most sensitive characteristics, whereas pseudopods, grayish-blue areas, and a whitish veil have been shown to be the most specific epiluminescence microscopic features for malignant melanoma. Sonography alone cannot reliably distinguish between different skin tumors. Preoperatively, the tumor thickness of 85% of the melanomas was assessed correctly concerning the pT stage. CONCLUSIONS: A 20-MHz ultrasound, in addition to epiluminescence microscopy, may improve the diagnostic accuracy by delivering information about depth and topographic location of skin tumors, but cannot give highly specific information about tissue dignity. It is a reliable tool for tumor thickness measurement for surgical planning. PMID- 7887658 TI - Comparison of the clinical informativeness of photographs and digital imaging media with multiple-choice receiver operating characteristic analysis. AB - BACKGROUND AND DESIGN: Electronic medical imaging is important for medical informatics, computerized learning, and especially for the growing field of telemedicine. The image resolution necessary for a clinical application can be determined by use of receiver operating characteristic (ROC) experiments. Completely profiling display systems is a tedious process, requiring multiple ROC experiments. We have developed a multiple-choice ROC analysis technique to compare the relative informativeness of digital image formats for a spectrum of cutaneous lesions simultaneously. The technique makes use of logical competitor sets (LCSs) of clinical conditions to redefine multiple-choice responses into the present/absent framework required for conventional ROC curve construction. The study divided 180 slides and digital images into three LCSs: pigmented lesions, flesh-colored papules, and papulosquamous conditions. Eight dermatologists diagnosed the lesions presented in two randomized viewing sessions. Accuracy profiles, independent of individual observer sensitivities, were derived from the responses. RESULTS: The informativeness of color slides and digital images was statistically similar, even when the conditions were stratified by difficulty of diagnosis. Results for nine specific skin conditions represented in the three LCSs were obtained simultaneously. CONCLUSIONS: Digital images appear to be as informative as slides for specific dermatologic diagnoses in the three LCSs tested. The use of LCSs allows stratification of results by diagnosis with greater efficiency than multiple repeated ROC experiments. Multiple-choice ROC analysis used in conjunction with logical competitor sets is the best currently available method for comparing imaging media for use in visual disciplines such as dermatology, radiology, pathology, and others. PMID- 7887657 TI - Epiluminescence microscopy. A useful tool for the diagnosis of pigmented skin lesions for formally trained dermatologists. AB - BACKGROUND AND DESIGN: Epiluminescence microscopy (ELM) is a noninvasive technique that, by employing the optical phenomenon of oil immersion, makes subsurface structures of the skin accessible for in vivo examination and thus provides additional criteria for the clinical diagnosis of pigmented skin lesions. At present, almost all studies about the value and clinical importance of ELM are based on data derived from ELM experts (ie, dermatologists specifically trained in this technique). In the present study, we attempt to determine whether the clinical diagnosis of pigmented skin lesions is significantly improved using ELM and whether ELM-trained individuals and dermatologists not trained in this technique profit equally from this technique. Randomly selected histologically proven pigmented skin lesion specimens, photographed with (ELM) and without oil immersion (surface microscopy) were presented by slide projection to six ELM experts and 13 ELM nonexperts (ie, dermatologists not formally trained in ELM) for diagnosis. To evaluate the diagnostic performance of ELM experts and nonexperts with and without the oil immersion technique (ie, ELM vs surface microscopy), the following parameters were obtained: intraobserver and interobserver agreement by kappa statistics and sensitivity and specificity of diagnostic performance. RESULTS: Our results show that by using the ELM technique the ELM experts reach a substantially better intraobserver agreement than nonexperts (median kappa, 0.56 vs 0.36). The interobserver agreement was markedly increased in the ELM experts group (average gain, 7%) but decreased in the ELM nonexperts group (average loss, 6%). The sensitivity of diagnosis was significantly increased in the ELM experts group (average gain, 10%), but decreased in the nonexperts group (average loss, 10%). Finally, the specificity of diagnosis was excellent in the ELM experts group, both with and without oil immersion (0.91) and was somewhat improved by ELM in the nonexperts group (0.77 vs 0.85). CONCLUSIONS: We conclude that the ELM technique increases sensitivity in formally trained dermatologists, but may decrease the diagnostic ability in dermatologists not formally trained in the ELM technique. Consequently, formal broad-based training in ELM should be offered to the dermatologic community. PMID- 7887659 TI - In vivo observation of magnified features of pigmented lesions on volar skin using video macroscope. Usefulness of epiluminescence techniques in clinical diagnosis. AB - BACKGROUND AND DESIGN: In vivo epiluminescence microscopy is now used as a useful noninvasive method for determining clinical diagnosis of pigmented skin lesions. Until now, however, pigmented lesions on the volar skin have been hardly studied with this method. In the present epiluminescent study, various kinds of pigmented lesions on the volar skin were extensively investigated by means of video macroscope, a newly developed electronic device with a higher magnification power, and correlation between the magnified features and histopathologic findings was evaluated. RESULTS: Magnified features of most lesions of acquired or congenital melanocytic nevus on the volar skin were classified into the following three typical patterns: (1) a parallel pattern formed by pigmented parallel lines corresponding to the furrows of the skin markings, (2) a latticelike pattern composed of pigmented lines along and across the furrows of the skin markings, and (3) a fibrillar pattern formed by densely packed, fibrillar pigmented lines arranged in the direction crossing the furrows. In contrast, macular or plaque portions of acral lentiginous melanoma exhibited disorderly arranged, irregular pigment patterns, mainly affecting the ridges of the skin markings. In addition, brown globules of various shades and many black dots of variable sizes were often observed and, on the margin of the lesions, pseudopods and/or the "serrated" pattern were detected. Cutaneous hemorrhagic macule and so-called black heel showed highly specific features and thus could be easily diagnosed with video macroscopy. CONCLUSION: Video macroscope proved to be a very useful instrument for the diagnosis of pigmented lesions on the volar skin. PMID- 7887660 TI - Treatment of advanced mycosis fungoides and Sezary syndrome with continuous infusions of methotrexate followed by fluorouracil and leucovorin rescue. AB - BACKGROUND AND DESIGN: The treatment of advanced mycosis fungoides is a therapeutic challenge. A variety of treatment approaches have been used. In our experience, chemotherapy has been most useful. The purpose of this study was to evaluate the effectiveness of the synergy previously demonstrated between methotrexate and fluorouracil in the treatment of advanced mycosis fungoides. Ten patients with mycosis fungoides and Sezary syndrome stages IIa (n = 1), II-b (n = 4), III (n = 1), IVa (n = 2), and IVb (n = 2) were treated with sequential methotrexate followed by fluorouracil and leucovorin rescue. Each patient received several courses of chemotherapy at varying intervals, as required for control of their disease. RESULTS: The duration of treatment ranged from 3 to 78 months, with an average duration of 33 months. The number of cycles of chemotherapy administered to each patient ranged from five to 45, with an average of 18 infusions per patient. The average survival in patients with tumors was 5.25 years, with a median survival of 6 years. Eight of 10 patients achieved at least 80% clearing and the remaining two achieved at least 60% clearing. Adverse reactions were minimal and included nausea and vomiting, mucositis, and leukopenia in only one patient. CONCLUSION: Sequential methotrexate and fluorouracil chemotherapy is an effective and safe treatment for advanced mycosis fungoides and Sezary syndrome. This regimen is extremely well tolerated, with minimal toxic side effects. PMID- 7887661 TI - Melanoma and vitiligo are associated with antibody responses to similar antigens on pigment cells. AB - BACKGROUND AND DESIGN: Several clinical observations suggest that there is a link between vitiligo and melanoma. We examined whether an immune response to similar antigens on pigment cells could account for this association. We tested 30 patients with melanoma, 29 patients with vitiligo, and 28 patients with unrelated conditions for antibodies to human melanocyte antigens using an immunoprecipitation sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis assay. RESULTS: Antibodies to melanocytes were present in 24 (80%) patients from the melanoma group, 24 (83%) patients from the vitiligo group, and in two (7%) patients from the control group. The antibodies in patients with melanoma or vitiligo were directed to similar antigens with molecular weights of approximately 40 to 45, 75, and 90 kd. The frequency of antibody responses to each of these antigens was similar in both diseases. By sequential immunodepletion, the antigens defined by antibodies in both diseases were similar. These antigens were also expressed on melanoma cells. CONCLUSIONS: Most patients with melanoma or with vitiligo develop antibodies to similar antigens that are present both on melanocytes and on melanoma cells. These findings support the hypothesis that the clinical link between the two diseases results from immune responses to antigens shared by normal and malignant pigment cells. PMID- 7887663 TI - Woringer-Kolopp disease (localized pagetoid reticulosis) or unilesional mycosis fungoides? An analysis of eight cases with benign disease. AB - BACKGROUND: The controversial nosology of Woringer-Kolopp disease (localized pagetoid reticulosis, unilesional mycosis fungoides) is being clarified by the systematic immunophenotypic and immunogenetic examination of infiltrating lesional T lymphocytes. The clinical course and immunohistochemical characteristics of eight cases of Woringer-Kolopp disease are described. OBSERVATIONS: Lesions measured 0.8 x 0.5 to 16.0 x 15.0 cm. Histologically, all cases resembled mycosis fungoides-type cutaneous T-cell lymphoma and phenotypic analysis supported their designation as an epidermotropic T-cell process. Phenotypic aberrancy was not noted on immunohistochemical analysis of paraffin embedded tissue. Three of four patients with available fresh-frozen tissue specimens demonstrated reduced or absent expression of CD7 (Leu-9) and/or Leu-8, while loss of the pan-T-cell markers CD2, CD3, and CD5 was not observed. Only in half these patients was a lesional predominance of CD4+ T-cells revealed. Germline DNA was detected in a lesional skin specimen obtained from one patient tested for T-cell receptor gene rearrangements. After treatment, the observation of disease-free periods ranging from 18 months to 17 years (mean, 5.9 years) reinforces the view that Woringer-Kolopp disease is a focal pathologic event with a favorable prognosis. No patient experienced a local recurrence or distant spread of the disease. CONCLUSION: This and previous studies suggest that Woringer-Kolopp disease is a unique, benign unilesional T-cell lymphoproliferative process with certain histologic and phenotypic similarities to both early epidemotropic mycosis fungoides-type cutaneous T-cell lymphoma and other T-cell lymphoproliferations. PMID- 7887662 TI - Differentiation and clonality of lesional lymphocytes in small plaque parapsoriasis. AB - BACKGROUND: Small plaque parapsoriasis is an idiopathic chronic dermatosis characterized by patches on the trunk and extremities that are often smaller than 5 cm in diameter and that sometimes have a digitate contour. These latter cases are often referred to as digitate dermatosis. Histopathologic examination reveals a mild superficial perivascular lymphocytic infiltrate associated with mild spongiosis and parakeratosis. To characterize this disease more completely, we analyzed the differentiation and clonality of lesional lymphocytes using immunohistologic and molecular biologic methods. OBSERVATIONS: We studied five cases using a frozen-section immunoperoxidase technique. In each case, there was a predominantly CD4+ T-cell infiltrate admixed with CD8+ T cells, Langerhans cells/indeterminate cells, and macrophages. In three cases, the clonality of lesional T cells was studied by denaturing gradient gel electrophoresis of polymerase chain reaction-amplified T-cell receptor-gamma gene rearrangements. Two cases showed a dominant clonal pattern, while one case exhibited a polyclonal pattern. Clinical follow-up disclosed persistent disease in one of the two clonal cases, while lesions in the other clonal case and the polyclonal case gradually resolved. CONCLUSIONS: Our findings indicate that small plaque parapsoriasis is a clinically indolent, histopathologically nonspecific, predominantly CD4+ T-cell mediated disease that, at least in some cases, contains a dominant T-cell clone. These features put small plaque parapsoriasis into a category with certain other members of the parapsoriasis group, namely, pityriasis lichenoides and lymphomatoid papulosis, which have been shown to be clonal T-cell disorders despite their clinically benign course. It remains to be determined if the dominant T-cell clones identified in some cases of small plaque parapsoriasis can ever be the direct precursors of overt cutaneous T-cell lymphomas. PMID- 7887664 TI - Lichenoid graft-vs-host disease in an autologous bone marrow transplant recipient. AB - BACKGROUND: Graft-vs-host disease (GVHD) represents one of the major complications of allogeneic bone marrow transplantation (BMT) but is less common in autologous BMT. Following autologous BMT, chronic GVHD has been reported in only four patients, all of whom had a self-limited sclerodermoid form. Lichenoid chronic GVHD has not been previously reported in an autologous BMT patient. OBSERVATIONS: Mucosal and cutaneous lichenoid lesions and histologic findings compatible with chronic lichenoid GVHD developed in a patient 35 days after autologous BMT was performed. The onset of clinical lesions at 35 days after BMT is not incongruent with the diagnosis of chronic lichenoid GVHD (rather than a graft-vs-host reaction) and may have been augmented by cyclosporin A in a manner similar to animal model experiments. CONCLUSION: All forms of GVHD can and do occur following autologous BMT. PMID- 7887665 TI - Small plaque (digitate) parapsoriasis is an 'abortive cutaneous T-cell lymphoma' and is not mycosis fungoides. PMID- 7887666 TI - An acquired vascular lesion in a child. Acquired progressive lymphangioma. PMID- 7887667 TI - Acneiform papules on the neck. Elastosis perforans serpiginosa (EPS). PMID- 7887668 TI - Leg ulcers and purple nail beds. Essential mixed cryoglobulinemia. PMID- 7887669 TI - Multiple papulocystic lesions on the trunk. Eruptive vellus hair cysts (EVHC). PMID- 7887670 TI - Overexpression of p53 in disseminated superficial actinic porokeratosis with and without malignant degeneration. PMID- 7887671 TI - Treatment of erythropoietic protoporphyria with N-acetylcysteine. PMID- 7887672 TI - Should dermatologists teach nondermatologists? PMID- 7887673 TI - Cutaneous thrombosis in human immunodeficiency virus type 1-positive patients and cytomegalovirus viremia. PMID- 7887674 TI - Itraconazole therapy for human immunodeficiency virus-associated eosinophilic folliculitis. PMID- 7887675 TI - Eosinophilic folliculitis associated with the acquired immunodeficiency syndrome responds well to permethrin. PMID- 7887676 TI - Acquired circumscribed hypertrichosis in the 'costaleros' who bear the 'pasos' during Holy Week in Seville, Spain. PMID- 7887677 TI - Absent transglutaminase TGK expression in two of three patients with lamellar ichthyosis. PMID- 7887678 TI - Palmoplantar keratoderma secondary to chronic acral erythema due to tegafur. PMID- 7887679 TI - Anetoderma may reveal cutaneous plasmacytoma and benign cutaneous lymphoid hyperplasia. PMID- 7887680 TI - Importance of human papillomavirus DNA typing in the diagnosis of anogenital warts in children. PMID- 7887681 TI - The last well family. PMID- 7887682 TI - Family experience with positive client response to clozapine. AB - To gain a better understanding of family member's subjective experiences to their relative's positive response to clozapine treatment, a qualitative descriptive study was conducted. Data were collected from 10 blood-related parents of clients who received treatment from a community mental health center's outpatient clozapine clinic. All family members felt that their relative had responded positively to clozapine treatment. Effects were described as subtle yet remarkable to family members. Family relationships improved as a result of the client's positive response, as the positive effects that the family members described largely had to do with the client's increased ability to relate to others, along with an increased interest and ability to participate in social activities. Finally, strong family advocacy seemed to be a major factor in this sample of clients having access to clozapine. PMID- 7887683 TI - A critical review of research on cognitive function/impairment in older adults. AB - Research on aspects of cognitive function and impairment in older adults is critically reviewed with the aim of evaluation and synthesis. The body of research on cognitive aging, mostly atheoretical, has not been placed within the larger context of cognitive sciences. Methodological concerns and lack of a unifying framework inhibit integration of previous studies and the development of a cohesive body of knowledge. Therefore, one paradigm of adult cognition, information processing, is recommended to further advance nursing theory and research. PMID- 7887684 TI - Clinical supervision: a three-way mirror. AB - The principles and process of a model of clinical supervision for psychotherapy are presented and described through two cases. The model draws heavily from Bowen's family systems theory and Peplau's theory of interpersonal relations. The relationships in the client-family, client-therapist, and therapist-supervisor systems mirror each other, and changes in self-definition, and in the management of anxiety of persons in one system catalyzes changes in parallel systems. Two cases illustrate the model. In the first case, anxiety needed to be raised to levels optimal for learning. In the second case, no learning occurred until levels of anxiety were reduced. PMID- 7887685 TI - Uniqueness within the nurse-client relationship. AB - The uniqueness of individual nurse-client relationships was explored by comparing therapeutic relationships of two different clients with the same nurse, and two different nurses with the same client. This secondary analysis included 38 nurses who had two different clients in the original study, and 13 clients who had two different nurses. Instruments included the Working Alliance Inventory, semantic differential scales related to the nurse's view of the client and the client's view of the nurse, and the Relationship Form. The same nurse working with two different clients had different preconceptions, and a different relationship with respect to bond, task, and goals with each client. There was a relationship between the time required to establish a therapeutic relationship with the two different clients. Clients working with two different nurses had no significant relationship on any of the relationship measures. Findings suggest that the same individual, whether a nurse or a client, experiences very different therapeutic relationships with different people. PMID- 7887686 TI - More than the sum of their parts: Martha Rogers and Hildegard Peplau. AB - Nursing practice is guided by a variety of theoretical models. Therefore, nursing theories are commonly selected by service institutions to focus practice. Both Rogers and Peplau made major contributions to the theory and practice of nursing, and both are appropriate models for the discipline of psychiatric and mental health nursing. This article explores the grand theory of Martha Rogers in conjunction with the use of the middle-range theory of Hildegard Peplau. Points of resonance, theoretical fit, and differences between theories are discussed. Appropriateness to practice of both theories are identified and the need for both perspectives is articulated. PMID- 7887687 TI - Adolescent depression: a review of the literature. AB - This article is a review of relevant literature concerning depression, a complex and multidimensional phenomenon that strikes adolescents in a variety of ways and with varying degrees of intensity. The definitions, prevalence, theoretical approaches, and related variables of adolescent depression are discussed. Finally, adolescent depression is discussed in relation to nursing process and nursing research. PMID- 7887688 TI - Cerebral blood flow values during cardiopulmonary bypass: relatively absolute or absolutely relative? PMID- 7887689 TI - What is meant by tetralogy of Fallot [S,D,I]. PMID- 7887690 TI - Evolution of the homograft valve. PMID- 7887691 TI - Expression of blood group antigen A by stage I non-small cell lung carcinomas. AB - To clarify the significance of blood group antigen A (BAA) expression by neoplastic cells, we studied patients who had curative resections of stage I non small cell lung carcinomas. Immunohistochemical staining using monoclonal antibodies was used to detect BAA expression by paraffin-embedded carcinoma cells. One hundred three patients were studied; mean age was 62.6 years, and 70 (68%) were male. Histologic types were as follows: adenocarcinoma, 52 (50.5%); squamous cell, 25 (24.3%); large cell, 24 (23.3%); and adenosquamous, 2 (1.9%). Histologic grades were as follows: I, 13 (12.6%); II, 26 (25.3%); and III, 64 (62.1%). All patients had American Joint Committee on Cancer stage I tumors: 65 patients (63.1%) had T1 tumors, and 38 (36.9%) had T2 tumors. Recurrences developed in 25 (24.3%) and metachronous malignancies in 4 (3.9%). Survival was 75% +/- 4.8% at 3 years and 66.6% +/- 7.5% at 5 years. Eighty-nine patients (86.4%) were blood group A and 14 (13.6%) were AB. Ninety-five (92.2%) were secretors of BAA and 8 (7.8%) were not. The expression of BAA by neoplastic cells was not detectable in 34 (33%), trace (1% to 5% of neoplastic cells) in 10 (9.7%), 1+ (6% to 25%) in 8 (7.8%), 2+ (26% to 50%) in 12 (11.7%), 3+ (51% to 75%) in 12 (11.7%), and 4+ (76% to 100%) in 27 (26.2%). The pattern of neoplastic cell staining was homogeneous in 14 patients (20.3%) and heterogeneous in 55 (79.7%). Carcinoma recurrence, overall survival, and event-free survival were not related to secretor status, BAA expression, or pattern of staining.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887692 TI - Associated atrial septal defects increase perioperative morbidity after ventricular septal defect repair in infancy. AB - Although closure of ventricular septal defects (VSDs) is currently associated with a relatively low risk, infants with associated atrial septal defects (ASDs) seem to have a higher perioperative morbidity. To clarify this impression, we reviewed our entire experience (since 1977) with closure of simple VSDs in 163 infants (age, < or = 12 months). Of these, 57 had significant ASDs (ASD-VSD subgroup). Hospital mortality was 3.7% (6/163) overall and 1.4% (2/145) since 1980. Actuarial survival at 10 years was 92% +/- 5%. Significant morbidity occurred in 15.5% (16/103) of the VSD subgroup versus 48.1% (26/54) of the ASD VSD subgroup (p < or = 0.001). Multivariate analysis identified the presence of multiple VSDs and early date of operation as risk factors for hospital death, and younger age, an associated ASD, the size of the VSD, and use of hypothermic circulatory arrest as risk factors for significant perioperative morbidity. Compared with the VSD subgroup, the ASD-VSD subgroup had a higher hospital mortality (5.3% [3/57] versus 2.8% [3/106]), were younger (5.1 +/- 2.9 versus 7.2 +/- 2.9 months; p = 0.001), had a higher preoperative pulmonary artery pressure (70.2 +/- 19.0 versus 62.7 +/- 21.8 mm Hg; p = 0.08), needed more inotropic support (12.3% versus 3.7%; p = 0.07), needed more prolonged ventilation (3.3 versus 1.8 days; p = 0.02), and had longer postoperative hospital stays (11 versus 8 days; p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887693 TI - AMPA glutamate receptor antagonism reduces neurologic injury after hypothermic circulatory arrest. AB - Pharmacologic inhibition of the N-methyl-D-aspartate (NMDA) glutamate receptor can reduce the neurologic injury associated with hypothermic circulatory arrest; however, other receptor subtypes, such as the alpha-amino-3-hydroxy-5 methylisoazole-4-propionic acid/kainate or AMPA/kainate subtype, may predominate in the adult brain. In this experiment, a selective AMPA antagonist, NBQX, was used in a canine survival model of hypothermic circulatory arrest. Twelve male dogs (20 to 25 kg) were placed on closed-chest cardiopulmonary bypass, subjected to 2 hours of hypothermic circulatory arrest at 18 degrees C, and rewarmed on cardiopulmonary bypass. All were mechanically ventilated and monitored for 20 hours before extubation and survived for 3 days. Six dogs received NBQX beginning 2 hours after arrest (3 mg/kg for 3 hours then 1.5 mg/kg for 2 hours). Control dogs received vehicle only. Neurologic recovery was assessed every 12 hours using a species-specific behavior scale that yielded a neurodeficit score ranging from 0 (normal) to 500 (brain dead). After sacrifice at 72 hours, brains were examined by receptor autoradiography and histologically for patterns of selective neuronal necrosis and scored blindly from 0 (normal) to 100 (severe injury). Dogs given NBQX had better neurologic function compared with controls (neurodeficit score, 58.6 +/- 15 versus 204 +/- 30; p < 0.004) and had less neuronal injury (18.2 +/- 3 versus 52.5 +/- 6; p < 0.004). Densitometric receptor autoradiography revealed preservation of neuronal NMDA receptor expression only in dogs given NBQX. These results suggest that antagonism of the non-NMDA glutamate receptor AMPA may be neuroprotective in adults after hypothermic circulatory arrest. PMID- 7887694 TI - Coronary artery disease in patients with type A aortic dissection. AB - The usefulness of preoperative coronary arteriography in patients with type A dissection of the aorta is controversial. To determine the prevalence of arteriosclerotic coronary artery disease in patients with type A dissection of the aorta, we reviewed our experience in 62 patients (42 with acute dissection and 20 with chronic dissection) who underwent operation between January 1, 1986, and December 31, 1993. Among 23 patients with acute dissection who underwent coronary arteriography, 8 (34.8%) had one or more coronary artery lesions causing a greater than 50% narrowing. Among 14 patients with chronic dissection who underwent coronary arteriography, 6 (42.9%) had one or more coronary artery lesions causing a greater than 50% narrowing. There were no fatal complications associated with coronary arteriography. Four patients with acute dissection and 6 patients with chronic dissection underwent coronary artery bypass grafting at the time of operative repair of the aortic dissection, with no operative deaths. On the basis of these findings and the success of combined coronary artery bypass grafting and aortic repair, we recommend that patients with an acute type A dissection who are in stable condition and all patients with a chronic type A dissection of the aorta should undergo preoperative coronary arteriography. PMID- 7887695 TI - Coronary arterial anatomy in double-outlet right ventricle with subpulmonary VSD. AB - We have examined 38 hearts with a double-outlet right ventricle with a subpulmonary ventricular septal defect. We divided the hearts into three groups according to the angle between the planes formed between the outlet septum and the remainder of the muscular ventricular septum; namely, at approximately right angles (15 hearts), parallel (11 hearts), and at an acute angle (12 hearts). The coronary arterial pattern corresponding to that seen in the normal heart was present in 11 hearts (73%) of the "right angle" group, in only one heart (8%) of the "acute angle" group, and in none of the "parallel" group. In contrast, the most common pattern in the setting of complete transposition was observed in none, 8%, and 91% of each group, respectively. Other diverse patterns were recognized in the hearts in the acute angle group, and the incidence of abnormal branching was significantly higher in this than in the other groups (p < 0.01). Knowledge of these anatomic variations in the course of the coronary arteries, some of which would cause problems at either definitive repair or reoperation, are essential for those seeking to achieve optimal surgical repair. PMID- 7887696 TI - Pulmonary injury after total or partial cardiopulmonary bypass with thromboxane synthesis inhibition. AB - Previous studies have shown an increase in left atrial plasma thromboxane (TBX) level and associated increase in lung injury parameters after total cardiopulmonary bypass (t-CPB) but not after partial cardiopulmonary bypass (p CPB). We used dazmegrel to study the effect of TBX synthesis inhibition on lung injury after t-CPB compared with p-CPB. Sheep were placed on t-CPB without ventilation and with pulmonary artery occlusion (n = 7) or p-CPB with ventilation and an unrestricted pulmonary artery (n = 7). All sheep were treated with dazmegrel. After 90 minutes we separated the sheep from CPB. Plasma TBX, platelets, white blood cells, protein concentration, lung lymph protein, flow, and pulmonary vascular resistance were measured before and after CPB. Lung biopsies were also obtained. Minimal derangement of these pulmonary parameters was seen after either p-CPB or t-CPB. Inhibition of TBX synthesis virtually eliminated the lung injury previously reported after t-CPB, when compared with p CPB. Clearly TBX has an important role in mediating lung injury after t-CPB. PMID- 7887697 TI - Determinants of hospital survival after cardiac transplantation. AB - To identify the preoperative factors that influence hospital survival after transplantation we analyzed our consecutive experience of 183 transplantations in 179 patients over a 10-year period. There were 151 male and 29 female transplant recipients ranging in age from 10 days to 70 years (mean, 48 +/- 1 years). Diagnoses included coronary disease in 110 patients, cardiomyopathy in 55 patients, valvular disease in 6 patients, and congenital heart disease in 9 patients. Seventy-seven had undergone a previous cardiac operation, and 30 patients required preoperative mechanical support. Forty patients received hearts from donors who were 40 years old or older (range, 40 to 62 years). Ischemic time was greater than 240 minutes in 32 cases, and pulmonary vascular resistance was greater than 3 Wood units in 40 patients (range, 3.1 to 10.0 Wood units). Cyclosporine induction was used in 52 patients, whereas 128 recipients received polyclonal antibody prophylaxis. There were 25 hospital deaths. Recipient diagnosis, use of mechanical support, donor age, and the immune suppression protocol were related to hospital survival according to univariate analysis. Using multiple logistic regression, only the method of immune suppression induction and the use of mechanical assists were significant independent determinants of survival. In conclusion, we believe that extended ischemic times and donor age do not adversely affect the early success of transplantation, whereas induction with immune globulin may reduce early mortality. Patients requiring mechanical support before transplantation continue to be a challenge. PMID- 7887698 TI - Structural and left ventricular histologic changes after implantable LVAD insertion. AB - Long-term support on the implantable left ventricular assist device (LVAD) produces structural changes in the recipient's heart. To assess the possibility of heart "recovery" we reviewed the records of 19 HeartMate LVAD recipients to determine structural and left ventricular histologic changes during LVAD support. Intraoperative transesophageal echocardiographic studies were performed in the operating room before LVAD insertion, immediately after LVAD insertion, and at explantation and heart transplantation (mean duration of support, 76 +/- 34 days). The initiation of LVAD pumping led to an immediate decrease (p < 0.001) in left ventricular dimensions, which were not significantly different by the time of device explantation. Left ventricular fractional shortening did not significantly improve during LVAD support (0.07 +/- 0.03 before LVAD; 0.11 +/- 0.10 immediately after LVAD; 0.11 +/- 0.11 before explantation). Histologic specimens showed a significant reduction in the number of wavy fibers, and contraction band necrosis (p < 0.01), both markers of acute myocyte damage. However, myocardial fibrosis increased (p < 0.05). Myocyte diameter increased slightly (p = 0.07). We conclude that implantable LVAD support is associated with immediate changes in ventricular structure. Histologic markers of acute myocyte damage improve, but fibrosis increases. Because the structural changes occur immediately, they do not indicate "recovery" of left ventricular function, but merely changes in loading conditions. PMID- 7887699 TI - Cerebral blood flow during cardiac operations: comparison of Kety-Schmidt and xenon-133 clearance methods. AB - This study simultaneously compared the standard Kety-Schmidt and the modified xenon-133 (133Xe) clearance techniques for measuring cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) during cardiac operations. The validity of the CBF method is important because our management of the patient during cardiopulmonary bypass (CPB) is based, in part, on our understanding of the cerebral hemodynamics during CPB. In 20 patients undergoing coronary artery bypass grafting, CBF and CMRO2 were determined by both methods. Measurements were made before onset of CPB and once during CPB. Ten patients underwent CPB with systemic normothermia (37 degrees C) and 10 with systemic hypothermia (27 degrees C). Anesthesia consisted of fentanyl and midazolam. CPB pump flows were kept at 2.2 to 2.4 L.min-1.m-2 and alpha-stat pH management was used. Xenon-133 clearance significantly underestimated CBF and CMRO2 relative to the Kety-Schmidt technique before CPB and at both bypass temperatures. Values obtained by 133Xe clearance were approximately 50% of that measured by the Kety-Schmidt method. The modified 133Xe technique as typically used during cardiac operations does not appear to measure CBF accurately; this leads to corresponding errors in CMRO2 calculations. Determination of CMRO2 and cerebral autoregulatory function during cardiac operations appears to be more appropriate if based on the more direct Kety Schmidt technique. Accordingly, our management of CPB with respect to cerebral perfusion as it has been determined by the modified 133Xe clearance method may require reassessment. PMID- 7887700 TI - Autologous reconstruction of pulmonary trunk at reoperation after extracardiac conduit repair. AB - Between 1991 and 1993, 5 patients underwent reoperation for critical stenosis of extracardiac conduit. Indication for extracardiac conduit repair was pulmonary truncal atresia in 3 patients and coronary anomaly including single left coronary artery and left anterior descending artery from right coronary artery in 2 patients. Age at reoperation ranged from 8 to 23 years (mean, 16.2 years). Preoperative systolic pressure ratio of right to left ventricles ranged from 0.83 to 1.05 (mean, 0.93), with the pressure gradient across the conduit ranging from 52 to 100 mm Hg (mean, 74.4 mm Hg). At reoperation, stenotic conduit was completely removed and central pulmonary artery was extensively mobilized. In 4 patients who had a relatively short distance (15 to 25 mm) between the pulmonary arterial stump and the right ventriculotomy incision, the distal pulmonary arterial stump was anastomosed directly to the cranial margin of the right ventriculotomy incision to serve as a floor mode of autologous tissue. In 1 patient with a long distance (40 mm), right ventricular-pulmonary arterial continuity was restored with a tailored autologous pericardial tube. There were no early or late deaths. Postoperative catheterization study revealed a satisfactory reduction of right ventricular pressure with the systolic pressure ratio ranging from 0.42 to 0.51 (mean, 0.47) and the pressure gradient across the right ventricular outflow tract ranged within 13 mm Hg (mean, 5 mm Hg). Restoration of right ventricular-pulmonary arterial continuity was successfully achieved by introducing the concept of autologous tissue repair even at reoperation instead of the insertion of new extracardiac conduit in patients with tetralogy of Fallot after extracardiac conduit repair. PMID- 7887701 TI - Bacterial wound colonization after broad-spectrum versus narrow-spectrum antibiotics. AB - Broad-spectrum versus narrow-spectrum antibiotic prophylaxis for patients who undergo cardiac operations is variously advocated to reduce the incidence of all infections or, conversely, to prevent resistant superinfections. Previous studies of prophylaxis have shown a reduction in the incidence of staphylococcal infections with some increased resistance. We studied preoperative and postoperative wound colonization as a surrogate for infection. Among 78 patients undergoing cardiac procedures, the type of prophylaxis was allocated as follows: narrow-spectrum (nafcillin), 24 patients; midspectrum (cephapirin), 26 patients; and broad-spectrum (ceftriaxone), 28 patients. Seventeen patients who underwent other procedures received no antibiotics and served as controls. Cultures of the operative site were done preoperatively, and 3 and 6 days postoperatively. The incidence of preoperative skin colonization with staphylococci was identical (95%) in all groups. Postoperatively, more patients receiving nafcillin (48%) were culture-negative for all organisms than were either of the other groups receiving antibiotics (27% and 22%) (p < 0.05). Gram-negative bacilli were infrequent colonizers and neither did the incidence of infection with these organisms increase nor did resistance develop in any group. The infection rates were not different among the treatment groups. Thus, a narrow-spectrum antistaphylococcal penicillin may offer an advantage in terms of both prophylaxis for cardiac operations and hospital costs. PMID- 7887702 TI - Influence of a delay on latissimus dorsi muscle flap blood flow. AB - The regional and total blood flow of canine latissimus dorsi muscle flaps (LDMFs) were examined to study the effect of a delay procedure, ligation of the perforators, before complete flap elevation. The regional blood flow of the middle and distal regions of the nondelayed LDMFs was poor and significantly lower than the proximal region at rest. The regional blood flow during the exercise test was improved and significantly higher in the middle (62% increase) and distal regions (187% increase) of the delayed LDMFs as compared with the nondelayed LDMFs. The mean total blood flow of the delayed LDMFs was 14 mL.min 1.100(-1) g at rest, increased to 30 mL.min-1.100(-1) g during exercise tests with intermittent burst electrical stimulation, and was maximal at 40 mL.min 1.100(-1) g immediately after the exercise. The phasic arterial blood flow of the delayed LDMFs was inhibited during contraction at 9 mL.min-1.100(-1) g, whereas it was 44 mL.min-1.100(-1) g during relaxation. In contrast, the phasic venous blood flow was accentuated during contraction to 32 mL.min-1.100(-1) g compared with 16 mL.min-1.100(-1) g during relaxation. PMID- 7887703 TI - Latissimus dorsi and serratus anterior dynamic descending aortomyoplasty for ischemic cardiac failure. AB - Dynamic descending aortomyoplasty for cardiac assistance is a form of extraaortic, skeletal muscle-driven counterpulsation. Controversy exists regarding its clinical applicability and the most suitable muscle autograft for the procedure. Specifically, the ligation of intercostal vessels required for descending aortomyoplasty may not be tolerated clinically. This study compared the hemodynamic profiles and long-term function of latissimus dorsi (LD) aortomyoplasty to a split serratus anterior (SA) descending aortomyoplasty in which all intercostal vessels were preserved. Descending aortomyoplasty was performed in 11 goats. In 5, the SA was harvested and its distal end divided, facilitating a wrap of the aorta without ligation of intercostal arteries. In 6, the LD was used as a circumferential aortic wrap. At 90 days, an occluder placed on the left anterior descending artery created an ischemic event. Hemodynamic studies with and without assistance were performed in the ischemic and nonischemic states. Latissimus dorsi aortomyoplasty improved cardiac output 24% and 5.6%, stroke volume 29% and 66%, left ventricular stroke work index 30% and 166%, and coronary flow 4% and 3% in the normal and ischemic heart, respectively. Serratus anterior aortomyoplasty improved cardiac output 36% and 10%, stroke volume 42.8% and 13.5%, left ventricular stroke work index 64% and 21%, and coronary flow 8% and 4.3%, in the normal and ischemic heart, respectively. Two of the SA autografts were fibrotic and nonfunctional at 3 months. Aortomyoplasty with either SA or LD muscle improves cardiac function in the normal and ischemic heart. However, divided SA is associated with a higher rate of fibrosis and may be less suitable for the procedure. PMID- 7887704 TI - Surgical treatment of childhood mediastinal tuberculous lymphadenitis. AB - Between 1985 and 1991, we treated 6 children, aged 2 months to 3 years, who required an invasive procedure for the management of complications caused by enlarged mediastinal lymph nodes secondary to tuberculosis. Radiologic and endoscopic studies revealed bronchial involvement by lymph nodes, with endobronchial granulomas and lobar or pulmonary obstruction in 4 patients and marked tracheal and esophageal stenosis produced by extrinsic compression in the remaining 2. Pathologic study of the lymph node or bronchial samples from the 6 patients disclosed granulomas with caseous necrosis and Langhans' giant cells. All the children were treated with a standard 6-month drug regimen consisting of isoniazid, rifampicin, and pyrazinamide. Five of the patients underwent thoracotomy for the purpose of nodal curettage or excision. In 1, upper right lobectomy and bronchoplasty were necessary. The sixth patient was treated by endoscopic resection of the granulomas. There was no postoperative morbidity, and radiologic and endoscopic evidence of resolution of the lesions was observed in all the patients. In our experience, surgical treatment, when performed as a coadjuvant treatment for tracheobronchial complications stemming from mediastinal tuberculous lymphadenitis, results in the resolution of the lesions and has no related morbidity. PMID- 7887705 TI - Prostacyclin and thromboxane levels in pleural space fluid during cardiopulmonary bypass. AB - Prostaglandins exhibit a variety of cardiovascular actions that may affect the hemodynamic recovery of the ischemic myocardium after cardiopulmonary bypass. We have observed a decrease in the mean arterial pressure on autotransfusion of the accumulated pleural cavity fluid during operation. One aim of this study was to determine the concentrations of prostacyclin and thromboxane A2 in the pleural cavity fluid by measuring their stable metabolites, 6-keto-PGF1 alpha and thromboxane B2, respectively, in 8 consecutive patients undergoing myocardial revascularization, and to compare them with the arterial levels. A second aim was to quantify the hemodynamic effect of the pleural cavity fluid during operation. The concentration of 6-keto-PGF1 alpha in the pleural cavity fluid was significantly higher than the arterial concentration (mean, 21.6 +/- 18.2 ng/mL; p < 0.01). The concentration of thromboxane B2 was also raised compared with the arterial concentration (mean, 3.62 +/- 5.96 ng/mL; p < 0.2). The percentage fall in the mean arterial pressure was 29.7% +/- 8.86% (p < 0.02), which was transient and lasted 1 to 3.5 minutes. The hemoglobin concentration, potassium level, and pH were also measured. This study shows that the pleural cavity fluid during cardiac operations contains significant amounts of endogenous prostacyclin. Considering the potential benefit of prostacyclin on the recovering myocardium, we believe that this fluid should be transfused as a volume replacement, keeping in mind the transient phase of hemodynamic instability. PMID- 7887706 TI - Experimental study on the optimum flow rate and pressure for selective cerebral perfusion. AB - The optimum flow rate and pressure for selective cerebral perfusion during moderate hypothermia (25 degrees C) were investigated in 36 mongrel dogs. Cerebral perfusion was performed for 90 minutes at a flow rate of 100% (the physiologic flow rate), 50%, 25%, and 0%, or no flow (cerebrocirculatory arrest). Somatosensory evoked potentials were monitored to assess brain function. An excess lactate level was considered an index of anaerobic cerebral metabolism, and histopathologic evaluation was performed. Somatosensory evoked potentials showed no abnormalities at flow rates of 100% and 50%, but became abnormal in some dogs at 25% and in all dogs under no-flow conditions. The excess lactate level only increased at a no-flow rate, but not significantly. Histopathologic evaluation showed no ischemic changes at flow rates of 100% and 50%, but there were slight ischemic changes at 25% and severe ischemic damage at no flow. The mean carotid arterial pressure was 63.1 +/- 5.9, 39.8 +/- 6.2, 24.9 +/- 6.0, and 11.3 +/- 3.5 mm Hg at a flow rate of 100%, 50%, 25%, and no flow, respectively. These results suggest that the safe range of flow rates for cerebral perfusion during moderate hypothermia is more than 50% of the physiologic level with a carotid arterial pressure of about 30 mm Hg or more. PMID- 7887707 TI - Comparison of the Carpentier and Duran prosthetic rings used in mitral reconstruction. AB - This clinical study was undertaken to evaluate the Duran flexible ring and the Carpentier rigid ring in terms of mitral annulus motion, transmitral flow and left ventricular function. Twenty-six patients (11 receiving rigid rings and 15, flexible rings) with normal sinus rhythm and with no or only trivial mitral valve regurgitation after surgical repair were selected. Angiograms demonstrated no significant differences in left ventricular systolic function between the two groups of patients. The area of the mitral annulus with the flexible ring significantly changed during the cardiac cycle. There were significant differences in the left ventricular fractional shortening (rigid ring, 35.8%; flexible ring, 43.4%) and in the peak velocity (rigid ring, 222 cm/s; flexible ring, 186 cm/s) at peak exercise. These data suggest that the flexible ring interferes less with the normal movements of the mitral annulus during the cardiac cycle, and that, under exercise conditions, it performs better than the rigid ring. We therefore conclude that mitral valve reconstruction using the Duran flexible ring is advantageous in patients with mitral regurgitation due to degenerative disease and sinus rhythm. PMID- 7887708 TI - Resternotomy for bleeding after cardiac operation: a marker for increased morbidity and mortality. AB - Over a 2-year period from January 1, 1992, to December 31, 1993, of 2,221 patients undergoing cardiac operations in our unit, 85 (3.8%) were reopened for the control of bleeding (9 patients more than once). The incidence of resternotomy in coronary cases was 2.3%, but resternotomy was more than three times as likely in valve cases (odds ratio, 3.4; 95% confidence interval, 2.1 to 5.4). Previous cardiac operation was more common among resternotomy patients than among the remainder (18% versus 9%, respectively; p = 0.018). An identifiable source of bleeding was found in 57 of the 85 patients (67%), but a concurrent coagulopathy was common (45 patients). Resternotomy patients, as a group, had higher preoperative risk scores (Parsonnet) than did the other patients (p < 0.0001), stayed longer in the intensive care unit (p < 0.0001), and had greater requirements for intraaortic balloon counterpulsation (14% versus 3%) and hemofiltration (9% versus 3%) (p < 0.0001 and p < 0.01, respectively). Nineteen resternotomy patients (22%) died in the hospital, a proportion significantly greater than the risk assigned to this group of patients preoperatively (12.8%) (p = 0.008). In contrast, the observed mortality for the other 2,136 patients (5.5%) was significantly less (8.3%) (p < 0.00006). Multiple forward stepwise logistic-regression analysis confirmed resternotomy for excessive bleeding after cardiac operation to be a significant independent predictor of a prolonged stay in the intensive care unit (p < 0.0001), the need for intraaortic balloon counterpulsation (p < 0.0001), and death (p < 0.0001). PMID- 7887709 TI - Safety of patent ductus arteriosus closure in premature infants without tube thoracostomy. AB - During a 30-month period, 34 premature infants underwent surgical closure of a patent ductus arteriosus. The mean gestational age at birth was 25 +/- 0.3 weeks and the mean age at the time of operation was 3 +/- 0.3 weeks (mean weight, 829 +/- 54 g). Indomethacin therapy had failed in 32 patients, and 2 had contraindications to its use. The initial 8 patients had parascapular incision and ligation of the patent ductus arteriosus; the last 26 patients had a short transaxillary incision and clipping. The average duration of the operation from the time of incision to skin closure was 36 +/- 2 minutes (range, 15 to 65 minutes). One patient (3%) needed chest tube insertion intraoperatively because of visceral pleura disruption. Two patients (5.8%) had a "small pneumothorax" (< 10% of the lung field) that resolved within 24 hours. There was no morbidity or mortality directly related to the operative procedure, although 3 patients (8.8%) ultimately died from problems related to their severe prematurity. We conclude that surgical closure of patent ductus arteriosus without chest tube drainage can be accomplished safely in premature infants. Postoperative nursing care is simplified and the cost is reduced because the need for the chest tube and drainage system is eliminated and the number of chest radiograms needed postoperatively is reduced. PMID- 7887710 TI - Tranexamic acid significantly reduces blood loss associated with coronary revascularization. AB - Four hundred fifteen patients undergoing coronary revascularization over a 12 month period were divided into two groups: 209 controls in the first 6 months received no tranexamic acid (TA) before cardiopulmonary bypass and 206 patients in the second 6 months received TA as a hemostatic agent. The demographics and the surgical techniques used were similar in the two groups. With TA there was a significant decrease in blood loss postoperatively, from 1,114.1 mL in the controls to 803.7 mL in those given TA (p < 0.001); in red blood cell use, from 1.7 units/patient in the controls to 0.69 units/patient in those given TA (p < 0.001); in fresh frozen plasma requirements, from 0.23 units/patient in the controls to 0.024 units/patient in those given TA (p < 0.01); and in platelet transfusion, from 1.06 units/patient in the controls to 0.30 units/patients in those given TA (p < 0.01). The percentages of patients not receiving any blood products were 65% in those given TA versus 49% in the controls (p < 0.01). There was no significant difference between the two groups in the incidence of perioperative myocardial infarction, cerebrovascular accidents, pulmonary embolism, or venous thrombosis to clearly suggest hypercoagulability. In this study, TA profoundly affected the coagulopathy associated with bypass in patients undergoing coronary revascularization. It significantly reduced blood loss and blood product transfusions. Any potential increased thrombotic complications could not be clearly demonstrated in this study, but should not be ignored. PMID- 7887711 TI - Overview of the nature of vasoconstriction in arterial grafts for coronary operations. AB - Many vasoconstrictors (spasmogens) may cause arterial graft spasm; however, there is lack of an overview of the nature of vasoconstriction in grafts. This study was designed to investigate the response of three major arterial grafts currently used for coronary artery bypass grafting to various vasoconstrictor substances. Segments of three arterial grafts (gastroepiploic [GEA], n = 28; internal mammary [IMA], n = 213; inferior epigastric [IEA], n = 24) taken from patients undergoing coronary artery bypass grafting were studied in organ baths under a physiologic pressure. Cumulative concentration-contraction curves were established for the following vasoconstrictor substances: endothelin-1, U46619, prostaglandin F2 alpha, norepinephrine, methoxamine, phenylephrine, 5-hydroxytryptamine, and potassium chloride (K+). In IMA, the highest contraction force was induced by U46619 (5.69 +/- 0.48 g), endothelin-1 (4.43 +/- 0.4 g), PGF2 alpha (6.29 +/- 1.42 g), and K+ (4.58 +/- 0.5 g). Internal mammary artery is highly sensitive to endothelin-1 (EC50, -8.13 +/- 0.08 log M) and U46619 (EC50, -8.21 +/- 0.21 log M) (lower than any other vasoconstrictors, p < 0.001). Next sensitive vasoconstrictors were PGF2 alpha and norepinephrine. 5-Hydroxytryptamine induced significantly higher contraction force in the IMA without endothelium (2.8 +/- 0.64 g versus 1.4 +/- 0.23 g, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887712 TI - Right atrial compression related to defibrillator patches. AB - Acceptable function of an internal defibrillator can be achieved with different patch orientations. For patients requiring defibrillator patches concomitant with a cardiac procedure requiring extracorporeal circulation, application of one of the patches within the pericardium adjacent to the right atrium has provided excellent defibrillation thresholds. We describe 4 such patients in whom a compressing thrombus subsequently developed between the patch and the atrium. The thrombus was small and asymptomatic in 1 patient, but caused localized tamponade requiring reexploration in 2 patients and a fatal superior vena caval obstruction in 1. The precise etiology of this serious complication remains unclear, but its occurrence argues against the application of intrapericardial defibrillator patches in this orientation. PMID- 7887713 TI - Implantation of transvenous pacemakers in infants and small children. AB - A series of 14 infants and small children ranging from 7 months to 7 years in age (mean, 2.5 years) underwent implantation of transvenous pacemaker systems. Three factors are of utmost importance in children: small subclavian vein size, thin subcutaneous layer in the chest, and growth. A five-point protocol is followed strictly: (1) duplex assessment of upper veins, (2) use of active fixation leads, (3) use of short (36 to 45 cm) leads, (4) anchoring of pulse generator with nonabsorbable material to prevent migration, and (5) routine use of the "lateral approach" in children more than 2 years old when the pulse generator is implanted in the chest. Because lead diameters measure 2 to 2.3 mm, a one-lead system needs a vein diameter of 5 mm (cross-sectional area of 19 mm2). A two-lead system needs a vein at least 7 mm in diameter and a cross-sectional area of 38 mm2 to prevent vein occlusion. Therefore all children less than 3 years of age had the leads implanted via the internal jugular vein. In 50% of children between 4 and 7 years of age, the internal jugular system also was used. Children more than 7 years old have leads implanted via the subclavian veins. Duplex ultrasound assessment of the upper veins is important to decide route of implantation. Use of short leads is recommended to reduce bulk at the pulse generator site. The "lateral approach" prevents problems at the generator implantation site. PMID- 7887714 TI - Effects of halothane on the immature lamb heart. AB - The choice of anesthesia during pregnancy and fetal operations is controversial. Halothane frequently is used, but its direct effects on fetal cardiac performance are unknown. The effects of halothane on fetal cardiac mechanics were studied in 8 fetal lamb hearts (135 days' gestation) using a modified Langendorff model connected to a membrane oxygenator. The perfusate consisted of oxygenated maternal blood at a constant flow temperature, hematocrit value, and glucose level. Coronary blood flow, left ventricular systolic pressure, left ventricular end-diastolic pressure, and the developed left ventricular pressure at a fixed volume were evaluated at baseline and after the addition of incremental concentrations of halothane to the perfusate through the oxygenator. Perfusate halothane levels were maintained in a clinical range. Systolic and diastolic cardiac function were adversely affected by the administration of even low doses of halothane, despite a concomitant increase in coronary blood flow. Because of the immaturity of their calcium transport system, fetal hearts may be particularly sensitive to the known calcium channel-blocking properties of halothane. PMID- 7887715 TI - Protection of the chronic hypoxic immature rat heart during global ischemia. AB - The benefit of cardioplegic cardiac arrest for the protection of immature myocardium is controversial. We therefore investigated the efficacy of (1) topical hypothermia alone, (2) slow cooling by coronary perfusion hypothermia, and (3) cardioplegic cardiac arrest for the protection of isolated immature rats hearts (28 days) during 8 hours of global ischemia at 10 degrees C. The study was conducted in hearts from rats that were kept hypoxemic by lifelong exposure to simulated high altitude. Left ventricular function, endothelial function, the metabolic status, and the extent of myocardial injury were all assessed. Topical hypothermia provided superior protection in hypoxic hearts, with recovery of the maximum developed left ventricular pressure by 70.6% +/- 18.0% (mean +/- standard deviation) of its preischemic value (p < 0.01 versus slow cooling and versus cardioplegic protection). The same pattern of recovery was observed among control hearts. The degree of recovery of endothelial function after sole topical hypothermia measured 54% +/- 36% in hypoxic hearts and 62% +/- 37% in control hearts, but was not recordable in any of the other groups. Creatine kinase leakage and the myocardial high-energy content did not differ significantly among any of the groups. Rapid cooling by topical hypothermia alone provides superior protection in chronic hypoxic, immature rat hearts versus the protection conferred by slow cooling. St. Thomas' Hospital cardioplegic solution II does not afford additional protection. Endothelial injury caused by cold asanguineous perfusates, including cardioplegia, interferes with the recovery of vascular function, which, in turn, may limit mechanical function. PMID- 7887716 TI - Percutaneous subcricoid minitracheostomy: report of 50 procedures. AB - A minitracheostomy is a small cannula in the trachea that allows permanent access to the tracheal lumen and that is used for the evacuation of bronchial secretions. It generally is performed through the cricothyroid membrane. We used a Seldinger technique in 50 patients to insert a minitracheostomy cannula in the subcricoid position. This technique proved to be easy to perform in translaryngeally intubated patients, both under local anesthesia and under general anesthesia. Operative complications occurred in 5 patients (10%), all of which were minor. The pros and cons of a minitracheostomy in the subcricoid position are discussed. PMID- 7887717 TI - Effect of cannula length on aortic arch flow: protection of the atheromatous aortic arch. AB - Atheromatous disease in the transverse aortic arch is associated with an increased incidence of perioperative stroke. In addition, tissue erosion in the aortic arch is caused by the high-velocity jet emerging from an aortic cannula during cardiopulmonary bypass (CPB), termed the "sandblast effect". To quantify this phenomenon, flow in the aortic arch was measured intraoperatively by epiaortic ultrasonography in 18 patients undergoing CPB. All were cannulated in the ascending aorta, 10 with a short (1.5 cm) cannula and 8 with a long (7.0 cm) cannula. The peak forward aortic flow velocities (mean +/- standard deviation) measured on the caudal luminal surface of the aortic arch were 0.80 +/- 0.23 m/s off CPB and 2.42 +/- 0.69 m/s on CPB (p < 0.001) for the short cannula and 0.53 +/- 0.20 m/s off CPB and 0.18 m/s on CPB for the long cannula. Thus, during CPB the peak forward aortic flow velocity with the short cannula was significantly greater (p < 0.001) than before CPB, whereas the long cannula produced a lower peak forward aortic flow velocity during CPB. Furthermore, Doppler examination revealed severe turbulence in the aortic arch in all patients with a short cannula. No arch turbulence, however, was seen in 7 patients with a long cannula, and only mild turbulence appeared in the remaining patient with a long cannula. These results show that use of a long aortic cannula results in a significant decrease in peak forward aortic flow velocity and turbulence in the aortic arch during CPB, which may reduce the risk of erosion or disruption of existing atheroma and ensuing embolic complications. PMID- 7887718 TI - Transesophageal echocardiography to evaluate patients with severe pulmonary hypertension for lung transplantation. AB - The surgical approach to lung transplantation for patients with severe pulmonary hypertension will be dependent on the primary disease and specific cardiac anatomy. To determine the safety and utility of transesophageal echocardiography in the management of patients with severe pulmonary hypertension who are being evaluated for lung transplantation, we studied 48 consecutive patients, aged 38 +/- 11 years, with pulmonary artery systolic pressure of 70 mm Hg or greater. All patients previously underwent left and right heart catheterization, transthoracic echocardiography, and radionuclide ventriculography. Transesophageal echocardiography was tolerated well by all patients. Additional data that significantly altered surgical therapy was found in 12 of 48 patients (25%): proximal pulmonary artery thrombi (3), patent foramen ovale with significant right to left shunting (2), atrial septal defect (2), double-outlet right ventricle (2), ventricular septal defect (2), and exclusion of atrial septal defect (1). These findings were confirmed surgically in all patients except 3, who died awaiting transplantation. Transesophageal echocardiography is useful in the evaluation of patients with severe pulmonary hypertension. PMID- 7887719 TI - Tepid antegrade and retrograde cardioplegia. AB - To determine the optimal temperature for the combination of antegrade and retrograde cardioplegia, 42 patients undergoing coronary artery bypass grafting were randomized to receive cold (9 degrees C; n = 14), tepid (29 degrees C; n = 14), or warm (37 degrees C; n = 14) blood cardioplegia delivered continuously retrograde and intermittently antegrade. Myocardial oxygen utilization, lactate and acid metabolism, and coronary vascular resistance were measured during the operation and cardiac function was assessed postoperatively. Myocardial oxygen consumption, lactate release and acid release were greatest with warm, intermediate with tepid, and least with cold cardioplegia (p = 0.0001). However, washout of lactate and acid at the time of cross-clamp release was reduced (p = 0.022) with tepid or cold compared with warm cardioplegia. Early postoperative left ventricular function was best preserved (p = 0.01) after tepid than after cold or warm combination cardioplegia. These results suggest that tepid combination cardioplegia reduced metabolic demands but permitted immediate recovery of cardiac function. This technique may provide better myocardial protection than cold or warm combination cardioplegia. PMID- 7887720 TI - Impact of autologous blood predonation on a comprehensive blood conservation program. AB - Preoperative autologous donation has been shown to be a highly effective measure in reducing homologous blood use in cardiac operations. The aim of our study was to verify the effectiveness of this procedure and to see whether it is compatible with a comprehensive blood conservation program. Three hundred forty-eight patients (group 1) donated an average of 657 +/- 199 mL of blood before open heart operation, whereas 344 patients (group 2) without autologous predonation were used as a control. The two groups were compared with regard to homologous blood use and the possibility of applying other blood conservation measures. Homologous transfusion rate in group 1 was 12.6%, whereas in group 2 it was 46% (p < 0.001). Patients with three units of predonated autologous blood had a transfusion rate of 0.8% (p < 0.001 compared with group 2). In group 1, acute normovolemic hemodilution was accomplished in a lower number of patients and with a lower average withdrawal (338 +/- 102 versus 403 +/- 145 mL; p < 0.001). Other blood conservation measures such as the return of mediastinal drainage and use of residual blood of extracorporeal circulation were applied with similar results in both groups. In our experience, preoperative autologous donation was compatible with the application of other blood conservation measures, but acute normovolemic hemodilution was achieved in a lower number of patients. Preoperative autologous donation proved to be a highly effective method for reducing banked blood use and therefore homologous blood exposure during and after cardiac operations. PMID- 7887721 TI - Potential complications of vascular stapling in thoracoscopic pulmonary resection. AB - In a series of 57 patients undergoing thoracoscopic pulmonary lobectomy, 2 required expeditious conversion to open thoracotomy when a stapling device (Endo GIA 30 V3; Autosuture, Ascot, UK) used on the main right lower pulmonary artery in 1 case and on the left superior pulmonary vein in the other cut but failed to staple the vessel involved. In both instances the vessel was successfully controlled while a thoracotomy was performed and the involved vessel was oversewn. Both patients made an uncomplicated postoperative recovery. As the number of thoracoscopic pulmonary resections increases, it is likely that similar episodes will occur in the future. These cases strongly emphasize the fact that patients undergoing this procedure should do so in a center specializing in thoracic surgery where there is the necessary surgical expertise and equipment to deal with such potentially life-threatening vascular complications. PMID- 7887722 TI - Surgical repair of severe bilateral branch pulmonary artery stenosis. AB - Management options for severe, bilateral branch pulmonary artery stenosis include percutaneous balloon dilation and direct surgical correction. Results with both balloon angioplasty and operation have been somewhat unpredictable. We report a case of staged surgical correction involving bilateral branch pulmonary artery reconstruction. PMID- 7887723 TI - Repair of traumatic tricuspid valve insufficiency by trabecular muscle elevation. AB - A technique is described for repair of traumatic tricuspid valve insufficiency; it was applied successfully in a young adult with a flail anterior leaflet due to chordal rupture. The technique consists of resuspension of the flail leaflet with autogenous trabecular muscle bundles and additional annuloplasty. PMID- 7887724 TI - Intracardiac extension of an intracaval sarcoma of endometrial origin. AB - A 52-year-old woman was diagnosed with a cardiac tumor by transesophageal echocardiography and magnetic resonance imaging. An intraoperative biopsy indicated the mass was low-grade endometrial stromal sarcoma. Successful tumor removal from the heart and inferior vena cava was accomplished with the use of hypothermic circulatory arrest. The chronically occluded infrarenal portion of the inferior vena cava was transected. The patient has no evidence of recurrent disease after a follow-up of 18 months and has no significant restriction in her daily activities. PMID- 7887726 TI - Tetralogy of Fallot [S,D,I]: successful repair without a conduit. AB - Tetralogy of Fallot [S,D,I] is a recently discovered form of tetralogy with solitus atria (S) and D-loop ventricles (D), but with inverted normally related great arteries (I). Because of infundibuloarterial inversion, the right coronary artery must traverse the stenotic pulmonary outflow tract, increasing the risk of surgical trauma to the right coronary artery. Here we report a case of successful surgical repair of tetralogy of Fallot [S,D,I] without the use of an extracardiac conduit. PMID- 7887725 TI - Wolff-Parkinson-White syndrome in a cardiac allograft. AB - A 61-year-old man underwent orthotopic heart transplantation for end-stage ischemic cardiomyopathy. The donor presented with Wolff-Parkinson-White syndrome and the allograft was successfully transplanted. The accessory pathway was interrupted postoperatively by radiofrequency current catheter ablation, and the patient is clinically well and free of preexcitation 24 months later. PMID- 7887727 TI - Transseptal decompression of the left heart during ECMO for severe myocarditis. AB - A 16-month-old boy suffered a cardiac arrest as a result of acute myocarditis, and venoarterial extracorporeal membrane oxygenation was instituted. Twelve hours later, acute left heart distention developed with cessation of left ventricular ejection. Under transesophageal echocardiographic guidance, a long introducer was placed into the left atrium through a transseptal puncture and connected in-line to the venous circuit. Within hours, left ventricular function improved and ejection returned. Left heart decompression was continued for 5 days, and the patient was weaned from extracorporeal membrane oxygenation after 6 days with normal cardiac and neurologic function. PMID- 7887728 TI - Acquired cor triatriatum after orthotopic cardiac transplantation. AB - Orthotopic cardiac transplantation was performed in a 42-year-old woman with idiopathic cardiomyopathy. Postoperative right ventricular failure developed and a transesophageal echocardiogram demonstrated acquired cor triatriatum with marked obstruction to mitral valve inflow and severe right ventricular dilatation. At reexploration, redundant donor atrial tissue was excised correcting the cor triatriatum. She was alive and well with normal hemodynamic parameters 12 months after transplantation. PMID- 7887729 TI - Endocarditis with multiple intracardiac shunts: identification and repair. AB - An 8-year-old boy who suffered from Hirschsprung's disease had development of tricuspid valve endocarditis that progressed to aortic root abscess formation, development of a fistulous communication between aorta and right atrium, atrial and ventricular septal defects, and a left ventricle to right atrium defect. Several surgical procedures were required. Operation consisted initially of closure of the septal defects and aortic valve repair. This was followed by homograft replacement of the aortic valve for persistent infection, and further closure of a left ventricle to right atrium fistula. PMID- 7887730 TI - Intraoperative prosthetic valve dysfunction: detection by transesophageal echocardiography. AB - We describe the valuable role of intraoperative transesophageal echocardiography in the detection of immediate prosthetic valve dysfunction. Transesophageal echocardiography accurately diagnosed one leaflet of a St. Jude Medical mitral valve to be stuck. We recommend routine transesophageal echocardiography for mitral valve operations. PMID- 7887731 TI - Coronary-to-coronary bypass using a free internal mammary artery: an alternative. AB - Paucity of conduit of adequate length or quality poses a dilemma in the occasional patient. We report such a patient, in whom we used a modified anastomotic technique using the normal right coronary artery for the proximal anastomotic site of a free right internal mammary artery graft. PMID- 7887732 TI - Fungal pulmonary abscess in an adult secondary to hyperimmunoglobulin E (Job's) syndrome. AB - Job's syndrome is characterized by recurring bacterial infections of the skin and sinopulmonary tract. Laboratory evaluation reveals consistent elevation of circulating immunoglobulin E levels. The syndrome has been reported as a rare cause of bacterial pulmonary abscess and pneumatocele formation in childhood; here we present a case of cavitating fungal abscess in an adult with Job's syndrome. PMID- 7887733 TI - Aortic dissection repair with GRF glue complicated by heart block. AB - Gelatin-resorcin-formaldehyde-glutaraldehyde (GRF) biologic glue is an available adjunct to repair acute ascending aortic dissections. Permanent complete heart block complicated the operative repair of 2 of 6 patients. The pathophysiology of heart block resulting from either the acute dissecting process or the technique of applying GRF glue is discussed. PMID- 7887734 TI - Technique for implantation of cardioverter defibrillators in the subpectoral position. AB - The downsized cardioverter defibrillators in early clinical trials in the United States are smaller and lighter than approved cardioverter defibrillators, but they remain relatively bulky. Prepectoral implantation of these devices may increase the risk of erosion, particularly in those patients with cardiac cachexia. This report describes a versatile technique for submuscular pectoral cardioverter defibrillator implantation using a lateral approach to the subpectoral space that has been used in 6 patients. Alternative surgical approaches for pectoral cardioverter defibrillator implantation and potential problems with these techniques are discussed. PMID- 7887735 TI - Pedicled pericardial fat pad: a useful hemostatic supplement. AB - Control of bleeding in areas difficult to suture because of tissue friability, edema, or calcification poses a serious problem in cardiac surgery patients. We report the use of a pedicled pericardial fat pad as an adjunct to the control of bleeding in these difficult-to-suture areas. This technique was used in 9 patients who were bleeding from different areas (the atria, coronary sinus, aorta, and myocardium), and the bleeding was completely and easily controlled. We consider the pedicled pericardial fat pad to be a useful supplement when suturing alone cannot effectively bring the bleeding under control. PMID- 7887736 TI - Adventitial inversion technique in repair of aortic dissection. AB - We describe a new technique for aortic anastomosis in the repair of acute dissection. The aorta is buttressed by inverting the adventitia without the use of Teflon or other synthetic materials. This technique provides a safe and secure anastomosis. PMID- 7887737 TI - Transesophageal echocardiography and adult cardiac operations. AB - Transesophageal echocardiography (TEE) now is used widely as a monitoring technique during and after cardiac operations. Widespread adoption of the technique has provided a wealth of new information. This review analyzes the influence of TEE on the routine conduct of cardiac operations and on surgical decision making in specific areas. Its use in routine hemodynamic monitoring and problem solving, both intraoperatively and postoperatively, is discussed. Transesophageal echocardiography has a particular role in valve operations, in guiding and assessing the immediate results of mitral valve repair. It also has found application in the grading and operative management of the severely atheromatous aorta, the diagnosis and management of aortic dissection, and other aspects of surgery of the thoracic aorta. In addition, management in specialized areas, such as cardiopulmonary transplantation and the insertion and monitoring of ventricular assist devices, have also been helped by the information provided by TEE. PMID- 7887738 TI - Video-assisted thoracic surgery. PMID- 7887739 TI - 1988: The muscle-powered dual-chamber counterpulsator: rheologically superior implantable cardiac assist device. Updated in 1995. PMID- 7887740 TI - Amiodarone and risk of cardiac operations. PMID- 7887741 TI - Single-clamp technique. PMID- 7887742 TI - Isolated bilateral coronary ostial stenosis with complete obstruction of the left main artery. PMID- 7887743 TI - Thoracoscopic intercostal nerve blocks. PMID- 7887744 TI - Intratracheal stent intubation under the assist of extracorporeal lung. PMID- 7887745 TI - Downsizing of valve allografts for use as right heart conduits. PMID- 7887746 TI - Two-suture technique for coronary bypass grafting. PMID- 7887747 TI - Myocardial protection. PMID- 7887748 TI - Cardiac hemangioendothelioma. PMID- 7887749 TI - Operative findings in failed button device closure of ASD. PMID- 7887750 TI - Use of internal mammary artery for coronary artery bypass grafts in the United Kingdom. PMID- 7887751 TI - The treatment of hypertension in women. AB - More women than men eventually develop hypertension, but they suffer less cardiovascular damage as a consequence. Primary hypertension in women has a greater volume component, often related to commonly associated obesity. Most lifestyle modifications have more to offer women, but women respond in a similar manner to various antihypertensive drugs. However, women appear to receive less benefit from antihypertensive therapy, as measured by morbidity and mortality data in multiple large clinical trials. Women who take oral contraceptives typically have a small rise in blood pressure, and in a small percentage, the rise is sufficient to induce hypertension. The prevalence is likely lower with currently used low-dose estrogen formulations. The use of estrogen for postmenopausal replacement therapy almost never raises the blood pressure, so that concerns about hypertension should not interfere with the use of this valuable therapy. PMID- 7887752 TI - The use and misuse of new antibiotics. A perspective. AB - Many new antimicrobial agents have become available recently. Several of the new antibiotics may offer an extended spectrum of activity or an improved toxic effect profile. However, they pose such problems as excessive cost and the emergence of drug-resistant organisms as a result of "selection pressure." The majority of common infections can be treated with conventional agents, either singly or in combination. A careful, bedside clinical evaluation, in conjunction with simple laboratory tests, often narrows down microbiologic possibilities and allows simpler antibiotic choices. This results in a cost-conscious approach of using conventional, inexpensive antibiotics in most situations, with new agents being reserved for judiciously selected indications. Such an approach will not only contain health care costs but will also help to preserve the microbiologic ecosystem. PMID- 7887753 TI - Financial incentives for organ procurement. Ethical aspects of future contracts for cadaveric donors. Council on Ethical and Judicial Affairs, American Medical Association. AB - Resolution 6, introduced at the 1993 Annual Meeting by the Medical Schools Section and referred to the Board of Trustees, called on the American Medical Association to review various options to enhance the availability of transplantable organs. The Council responds with this report and with a companion report on mandated choice and presumed consent for organ donation. PMID- 7887754 TI - How bad are bacteremia and sepsis? Outcomes in a cohort with suspected bacteremia. AB - BACKGROUND: To evaluate the short-term and long-term outcomes of patients with suspected bacteremia, we performed a prospective cohort study. METHODS: Clinical data were collected within 24 hours of initial culture from a random sample of 1516 episodes in which blood cultures were performed in an urban tertiary care hospital. One hundred forty-two patients with bacteremia were compared with two comparison groups: (1) 142 randomly selected patients with negative cultures, matched in age within 5 years, gender, severity of underlying disease, and presence of major comorbidity, and (2) all 155 patients with contaminant cultures. The main outcome measures were death, death secondary to bacteremia, and major complications. RESULTS: In the 439 patients, there were 142 deaths (32%), 114 at 1 year (26%) and 46 within 30 days (11%). Mortality at 30 days was most highly correlated with predicted fatality of underlying disease: 48% for the 65 patients with a rapidly fatal disease, 9% for the 156 patients with an eventually fatal disease, and 0.5% for the 217 patients with no fatal disease. In a Cox survival analysis, the risk ratio associated with bacteremia was 1.6 (95% confidence interval, 1.0 to 2.4) vs the comparison groups. When we performed time dependent Cox analyses in which the hazard ratio was allowed to change at 30 days, we found that the risk ratios associated with bacteremia were 2.3 (95% confidence interval, 1.2 to 4.4) for the first 30 days, and 1.3 (95% confidence interval, 0.76 to 2.1) after 30 days. CONCLUSIONS: We conclude that this population has a high mortality, which is strongly correlated with severity of underlying disease. Short-term mortality was higher in patients with bacteremia even after controlling for severity of illness, but the increase in risk was present only during the first month and most deaths occurred in patients with a rapidly fatal disease. PMID- 7887755 TI - Treatment of deep venous thrombosis with low-molecular-weight heparins. A meta analysis. AB - BACKGROUND: An intravenous course of unfractionated heparin adjusted on the basis of the activated partial thromboplastin time is the initial treatment of choice for most patients with venous thromboembolism. Recently introduced low-molecular weight heparin preparations can be administered subcutaneously, once or twice daily, without laboratory monitoring. We quantitatively assessed the relative efficacy and safety of low-molecular-weight heparin vs standard heparin for the initial treatment of deep venous thrombosis. METHODS: English-language reports of randomized trials were identified through a MEDLINE search (1984 through 1994) and a complementary extensive manual search. Reasons for exclusion from the analysis were no heparin dosage adjustments, the lack of use of objective tests for deep venous thrombosis, duplicate reports, preliminary reports of data later presented in full, dose-ranging studies that used higher doses of low-molecular weight heparin than are currently in use, and the failure to provide blind end point assessment. We assessed the incidence of symptomatic recurrent venous thromboembolic disease, the incidence of clinically important bleeding, and mortality. RESULTS: Ten of the 19 identified trials satisfied the predetermined criteria. The relative risk reductions for symptomatic thromboembolic complications (53% [95% confidence interval, 18% to 73%]), clinically important bleeding (68% [95% confidence interval, 31% to 85%]), and mortality (47% [95% confidence interval, 10% to 69%]) were all statistically significantly in favor of low-molecular-weight heparin. CONCLUSIONS: Low-molecular-weight heparins administered subcutaneously in fixed doses adjusted for body weight and without laboratory monitoring are more effective and safer than adjusted-dose standard heparin. Since low-molecular-weight heparins may not be interchangeable and the conclusions of our meta-analysis are based mainly on the findings of three trials that used two different low-molecular-weight heparins, definitive randomized controlled trials for the other low-molecular-weight heparins are required. PMID- 7887756 TI - Perceived and actual risks of driving in patients with arrhythmia control devices. AB - BACKGROUND: We surveyed patient attitudes about driving and about driving restrictions for patients with automatic defibrillators and pacemakers, and we assessed risk of arrhythmias occurring during driving. METHODS: One hundred two patients responded to a questionnaire (57 patients with defibrillators and 45 patients with pacemakers) about driving habits and opinions on restriction of patients who have devices and want to drive. In addition, the literature was reviewed for approximate incidences of sudden death and syncopal or nonsyncopal device therapy to estimate risk while driving of having a defibrillator discharge. RESULTS: Thirty-two patients with defibrillators (56%) and 28 patients with pacemakers (62%) currently drove an average of 196 and 161 km/wk, respectively. Most patients felt that driving was a right and 75% felt that restriction imposed a hardship on them. Respondents felt that common sense, limited distances, or physician input should set driving limitations. A minority felt that no restrictions should be placed on these drivers or that they should not drive at all. The risks of sudden death and syncopal and nonsyncopal defibrillator discharge were estimated at 0.0009%, 0.0011%, and 0.0015% per kilometer driven, respectively, based on weekly kilometers and published occurrences of these phenomena. CONCLUSIONS: Patients perceive that driving is their right and that there is a low risk of an arrhythmic event behind the wheel. The estimated risk and published accounts of sudden death support this. However, concurrent medical problems and stresses imposed by driving may increase risk. The physician must make reasonable recommendations to ensure patient and public safety, keeping in mind both state and federal driving regulations and reporting requirements. PMID- 7887757 TI - Effects of acute psychological stress on serum lipid levels, hemoconcentration, and blood viscosity. AB - BACKGROUND: While there is substantial evidence that psychological stress enhances risk for coronary artery disease, the mechanisms underlying such an influence remain unclear. We examined the effects of short-term psychological stress on serum lipid levels, hemoconcentration, fibrinogen level, and plasma viscosity. METHODS: Forty-four healthy young adults were randomly assigned to perform a distinctly frustrating cognitive task for 20 minutes (stress condition) or to rest quietly for the same period (control condition). RESULTS: Relative to controls, stressed subjects showed significant increases in blood pressure and heart rate; total, low-density, and high-density lipoprotein cholesterol levels; hematocrit; hemoglobin level; and total protein concentration. Stressed subjects also showed significant reductions in plasma volume and increased plasma viscosity and estimated whole-blood viscosity compared with controls. A similar trend in fibrinogen level was not statistically significant. Individual differences in blood pressure and heart rate response to stress correlated highly with changes in total cholesterol levels and hematocrit. CONCLUSIONS: Our investigation provides further evidence that exposure to short-term mental stress elicits hemoconcentration with associated increases in serum lipid concentrations, hemostatic factors, and blood viscosity. PMID- 7887758 TI - Evaluation of early (5 to 6 hours) iodine 123 uptake for diagnosis and treatment planning in Graves' disease. AB - BACKGROUND: Twenty-four-hour radioactive iodine uptake measurements necessitate extra visits and time delays in diagnostic confirmation of and therapy planning for hyperthyroid patients. We evaluated the early (5 to 6 hours) measurement of iodine 123 uptake (EU) to predict late (24 hours) uptake (LU) and assessed its value in the management of hyperthyroidism. METHODS: We conducted a prospective study in 51 previously untreated hyperthyroid and 27 euthyroid patients (initial evaluation group). Patients underwent both 6- and 24-hour 123I uptake measurements. A subsequent 21 patients with Graves' disease (confirmation group) were evaluated in light of regression data generated in the initial evaluation group. RESULTS: An EU value of greater than 20% had a sensitivity of 100%, a specificity of 96%, and a positive predictive value of 98% for the diagnosis of hyperthyroidism and was superior to the most predictive LU value (> 30%), which had a sensitivity of 98%, a specificity of 89%, and a positive predictive value of 94%, in distinguishing the hyperthyroid patients from euthyroid patients or those with subacute thyroiditis. Regression analysis revealed that the 24-hour uptake of the hyperthyroid patients could be predicted from the early measurement with the following formula: LU = 28.94 + 0.584 (EU). The measured EU of the confirmation group was used to calculate a predicted LU with use of this formula. Measured LU and predicted LU correlated well (r = .85, P < .001). Iodine 131 dose calculations were performed post hoc; LU calculated doses correlated with predicted LU doses (r = .91, P < .001). Mean dose differences were small. CONCLUSIONS: The EU of 123I can replace 24-hour uptake measurements. Early uptake measurement is reliable and clinically useful for diagnosis confirmation and treatment planning in thyrotoxic patients. PMID- 7887759 TI - Enhancing physician adoption of practice guidelines. Dissemination of influenza vaccination guideline using a small-group consensus process. AB - BACKGROUND: A dissemination intervention to facilitate adoption of a preventive practice guideline (influenza vaccination for older adults) in group practices was developed and evaluated. The intervention, small-group consensus process, started with a physician expert presenting the guideline and followed with the group participating in a structured discussion of ways to implement the guideline that culminated in a public commitment (ie, "buy in") to adopt the guideline. METHODS: Thirteen group practices and their primary care physicians (mean size, 5) were assigned randomly to intervention or control arms. In each group practice, physicians in the intervention arm met for 1 hour. Control physicians participated in an unrelated discussion (non-steroidal drug use). Guideline adoption was determined by changes in physicians' vaccination rates that were obtained through prechart and postchart reviews of 51 physicians. Prequestionnaires and postquestionnaires measured influenza knowledge and prevention attitudes. RESULTS: Using analysis of covariance, the small-group consensus process was found to increase physician vaccination rates by 34% compared with the control arm (F (1,48) = 19.49). All intervention arm physicians increased vaccination rates from before to after compared with 54% of control arm physicians. Attitudes and knowledge did not change and were unrelated to increased vaccination rates. CONCLUSIONS: A case is made for the small-group consensus process as an effective utilization-focused dissemination method. Interventions based on group dynamics and sensitive to local practice contexts can be useful in facilitating adoption of guidelines by physicians in group practices. PMID- 7887760 TI - Decisions about life-sustaining treatment. Impact of physicians' behaviors on the family. AB - BACKGROUND: Despite the growing availability of advance directives, most patients in the intensive care unit lack written directives, and, therefore, consultation with families about treatment decisions remains the rule. In the context of decision making about withdrawing life-sustaining treatments, we investigated which physician and nurse behaviors families find supportive and which behaviors increase the family's burden. METHODS: We conducted intensive 1- to 2-hour-long individual interviews using a semistructured interview protocol with 32 family members of patients without advance directives whose deaths followed a stay in the intensive care unit and withdrawal of treatment. We analyzed more than 700 pages of verbatim interview data using content analysis techniques and achieved more than 90% interrater agreement on data codes. RESULTS: Themes emerged as families identified selected physician and nursing behaviors as helpful: encouraging advanced planning, timely communication, clarification of families' roles, facilitating family consensus, and accommodating family's grief. Behaviors that made families feel excluded or increased their burden included postponing discussions about treatment withdrawal, delaying withdrawal once scheduled, placing the full burden of decision making on one person, withdrawing from the family, and defining death as a failure. CONCLUSIONS: Study findings provide an increased understanding of the unmet needs of families and serve to guide physicians and nurses in reducing actions that increase families' burdens as they participate in treatment withdrawal decisions. PMID- 7887761 TI - Disagreement with a hedged survey question does not tell us much. PMID- 7887762 TI - Pamidronate for cancer-associated hypercalcemia. PMID- 7887763 TI - ACE inhibitors after acute myocardial infarction. PMID- 7887764 TI - Paroxetine-induced priapism. PMID- 7887765 TI - Diabetes mellitus following intravenous pentamidine administration in a patient with HIV infection. PMID- 7887766 TI - [The effort to incorporate quality of life into rectal cancer surgery]. PMID- 7887767 TI - [Study on cases with primary traumatic oculomotor nerve palsy]. PMID- 7887768 TI - [Perioperative management of coagulation and fibrinolytic activity in endosaccular embolization of cerebral aneurysms]. AB - Endosaccular embolization is an innovative and effective treatment for surgically formidable cerebral aneurysms. Platinum microcoils are soft, easily fit to complex configuration of aneurysms, highly thrombogenic, so that suitable for this purpose. Recently developed Guglielmi detachable coils have more advantages in terms of retrievability and electrothrombotic effect. However, distal migration of intraaneurysmal thrombus produces thromboembolism in normal cerebral arteries, leading to neurological deficits. Three cases are presented in which thromboembolic complications occurred during or after embolization of cerebral aneurysms with platinum microcoils. Emergent fibrinolytic treatment resolved neurological deficits in each case without any other complications. From these lessons, a protocol of intra- and postoperative anticoagulation and antiplatelet therapy is presented. In conclusion, perioperative management of fibrinolytic and coagulation activity is extremely important in preventing thromboembolic complication and obtaining successful result. PMID- 7887770 TI - Intraductal papillary-mucinous tumors of the pancreas. PMID- 7887769 TI - [Results of surgical treatment of aortic dissections]. AB - From January 1989 to September 1993, 59 consecutive patients (35 males and 24 females, mean age 59.6 years old) underwent surgical repair of aortic dissection on the cardiovascular surgical unit at Takeda Hospital. The type of aortic dissection were classified according to Stanford University criteria. Twenty-two patients had acute type A (Ac-A), 10 had chronic type A (Ch-A), 4 had acute type B (Ac-B), and 23 had chronic type B (Ch-B) dissection. Seventeen dissections (29%) in the entire group of 59 cases had ruptured (including cardiac tamponade, pleural effusion and hemoptysis etc.). Ischemia of lower extremity occurred in 7 patients and ischemia of visceral organs in 3 patients. Type A dissection were approached via a median sternotomy and cardiopulmonary bypass with systemic hypothermia. Type B dissections were approached through a left postrolateral thoracotomy. Left heart bypass (left atrial-femoral in 8 cases) and partial cardiopulmonary bypass (femoral-femoral in 12 cases) generally were utilized. Resection of intimal tear and replacement of aorta with vascular grafts (including aortic arch in 19 cases) were performed in most patients and primary closure of the intimal tear was performed in 9 cases using GRF. The over-all operative mortality rate was 36% (8/22) for Ac-A, 20% (2/10) for Ch-A, 25% (1/4) for Ac-B, 22% (5/23) for Ch-B. Main causes of operative death was perioperative brain damage. It is necessary to improve the operative mortality for Ac-A dissections (especially in replacement of aortic arch and arch vessels). Further researches are needed regarding optimal methods of the cerebral protection during reconstruction of aortic arch. PMID- 7887771 TI - Hodgkin's disease associated with localized or multicentric Castleman's disease. PMID- 7887772 TI - Complete blood count specimen acceptability. A College of American Pathologists Q Probes study of 703 laboratories. AB - OBJECTIVE: to determine the frequency and reasons for rejection of specimens submitted to the laboratory for complete blood count studies. DESIGN AND SETTING: College of American Pathologists' Q-Probes laboratory quality improvement study prospective recording of rejected complete blood count specimens and associated factors in 703 laboratories. MAIN OUTCOME MEASURE: Percentage of submitted specimens rejected for testing. RESULTS: Of 7,894,882 complete blood count specimens submitted for testing to the participating laboratories during the data collection period, 35,347 (0.45%) were rejected. The most frequent reason for rejection was a clotted specimen, which occurred about six times more frequently than the second most cited reason, insufficient specimen quantity. Compared with their respective frequency of use for specimen collection, significantly more rejected specimens were collected in microtubes than in other containers. Compared with the respective frequency with which they collect specimens, laboratory personnel had significantly fewer rejected specimens than the other personnel groups. The poorest performance was exhibited by other in-hospital nonlaboratory personnel. Hospital bedsize was also a significant performance factor; smaller hospitals demonstrated lower rejection percentages. CONCLUSIONS: Specimen rejection should be monitored on a regular basis, identifying institution-specific factors that are associated with rejection. Monitoring of sufficient significant variables will help narrow the focus of corrective action. Action thresholds should be set sufficiently low to assure ongoing efforts toward improvement. PMID- 7887773 TI - Intraductal papillary-mucinous neoplasm of the pancreas. A clinicopathologic entity. AB - AIMS: The main clinicomorphologic findings from two new cases of intraductal papillary-mucinous neoplasm of the pancreas were analyzed and discussed. METHODS: Formalin-fixed pancreatic tissues from the more representative areas were routinely stained. An electron microscopic examination was performed in case 2 on glutaraldehyde-fixed tissue fragments. RESULTS: Both patients had a long history of symptoms that was suggestive of chronic pancreatitis. At endoscopic retrograde pancreatography a dilatation of the main duct was observed. Ultrasonography revealed cystic dilatations that were interpreted as pseudocysts. The patients underwent total pancreatectomy. The gross appearance showed no mass, but the pancreas was enlarged and diffusely hard. The cut surface showed micromacrocysts filled with soft friable tissue and mucus. Histological examination revealed diffuse neoplastic papillary proliferations within ectatic and cystically dilated ducts. The lesions exhibited varying grades of atypia and foci of in situ carcinoma. No clear evidence of invasion or lymph node metastases were observed. The nontumorous pancreas showed diffuse and multiple hyperplastic papillary changes in the ductal tree. CONCLUSION: The main clinicopathologic findings of intraductal papillary-mucinous neoplasm of the pancreas have been reported. Our study favors the hypothesis that chronic pancreatitis and/or ductal epithelial papillary hyperplasia may play a role in the pathogenesis of this tumor. We have emphasized the cystic appearance and mucinous features of this neoplasm, and so we suggest the use of the term intraductal papillary-mucinous neoplasm. PMID- 7887774 TI - A spectrum in the pathology of toxoplasmosis in patients with acquired immunodeficiency syndrome. AB - We describe a variety of toxoplasmic lesions in seven patients with the acquired immunodeficiency syndrome. The first patient had multiple small-intestinal ulcers associated with Toxoplasma tachyzoites and high antibody titers; he died of disseminated histoplasmosis. The second patient, who died of tuberculosis, also had an inactive chronic Toxoplasma infection, with tissue cysts in the brain that were associated with glial nodules. A third patient died of Toxoplasma encephalitis, manifested by multiple foci of necrosis associated with Toxoplasma tachyzoites, cysts, and hypertrophic arteritis. A fourth patient had been treated for toxoplasmic encephalitis with co-trimoxozol (trimethoprim-sulfamethoxazole combination) for 3 to 4 days and showed degenerating tachyzoites associated with necrotic areas. A fifth patient, treated for toxoplasmic encephalitis with co trimoxazol for 14 days, had necrotic lesions associated with Toxoplasma antigen and a few cysts. A sixth patient with encephalitis and Toxoplasma tachyzoites and young cysts in the biopsy showed healed brain lesions after 22 days of treatment. A seventh patient, diagnosed radiologically and serologically with Toxoplasma encephalitis, was treated for 7 months; his ring-enhancing lesions subsided, and he died of a central nervous system lymphoma. Toxoplasma could not be isolated from the brain, although toxoplasmic DNA was detected in the brain and heart by polymerase chain reaction. The pathogenesis of the range of these lesions, their diagnosis, and the possibility of terminating Toxoplasma infection by prolonged chemotherapy are discussed. PMID- 7887775 TI - False-positive immunoreactivity with muscle-specific actins in non-Hodgkin's lymphomas. AB - Antibodies to forms of muscle actin have been developed that are highly specific for tissue of myogenic origin and for which false-positive reactions are seldom reported. We studied 23 cases of B-cell malignant lymphoma by immunohistochemistry using monoclonal antiactin antibodies of two different specificities. Eight of the 23 cases were positive with an antibody against smooth-muscle actin that had been produced as ascitic fluid. Reactivity was abolished by the use of antibody from the same clone (1A4) but produced as a tissue culture supernatant. Nine of 23 cases were positive with an antibody against muscle actin (clone HHF35) produced as ascitic fluid. An antibody from the same clone (HHF35), but produced as a tissue culture supernatant, gave weak staining of both lymphoid cells and connective tissue background. Lymphoma staining by both HHF35 antibodies (and background staining) was abolished by the addition of ethylenediaminetetraacetic acid (EDTA) to the antibody. (EDTA is reported to eliminate nonspecific protein binding.) Each ascitic fluid-derived antibody stained the lymphomas in an apparently specific manner. There was intense granular deposition of reaction product localized to specific portions of the cell (plasma membrane or diffuse cytoplasmic staining and, in two signet ring cell lymphomas, globular staining of intracytoplasmic inclusions), and there was substantial concordance of the staining of the two antibodies. This finding of false-positive reactivity by two different antiactin monoclonal antibodies, both prepared as ascitic fluid, supplements recent reports of a similar phenomenon with ascitic fluid preparations of the antimelanoma monoclonal antibody HMB45.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887776 TI - The cytologic evaluation of lipid-laden alveolar macrophages as an indicator of aspiration pneumonia in young children. AB - Gastroesophageal reflux with aspiration of feedings in infants and young children may be involved in the development of chronic lung damage. Our laboratory has utilized tracheal aspirates stained with oil red O to identify and quantitate lipid-laden alveolar macrophages as a marker of such aspiration. During the last 10 years, we have evaluated 244 tracheal aspiration smears in children. Although a few patients were up to 3 years old, the vast majority were infants. The cytologist looked for the presence of and the number of oil red O-positive macrophages on tracheal aspirate smears. The specimens were easily assigned grades of absent (grade = 0), low positive (grade 1: 1-25 lipid-laden macrophages), moderate positive (grade 2: 26-50 lipid-laden macrophages), and high positive (grade 3: > 50 lipid-laden macrophages). The grade was then correlated with the positive or negative clinical diagnosis of gastroesophageal reflux with aspiration. We believe the cytologic evaluation and grading of oil red O-stained tracheal aspirates for lipid-laden macrophages is valuable in identifying these patients with gastroesophageal reflux and aspiration. PMID- 7887777 TI - Detection of silica particles in lung tissue by polarizing light microscopy. AB - The detectability of silica particles in ordinary histologic sections by means of polarizing light microscopy has been controversial. Through the application of both correlative light microscopy and scanning electron microscopy to different lung sections, we showed that particles demonstrating peaks for silicon only by energy-dispersive x-ray microanalysis were in fact visible by polarizing light microscopy. These particles included some silica particles less than 1 microns in diameter. We found no correlation between the intensity level of the light source used for polarization and the differential ease of visualizing silica versus silicates; examples of both could be detected at both relatively low and high light intensities. This suggests that geometric parameters may be as important as composition in the ease of detection of silica versus silicates with polarized light. PMID- 7887778 TI - Expression of interleukin-1 receptor antagonist protein in malignant lymphomas. An immunohistochemical study. AB - OBJECTIVE: Interleukin-1 (IL-1) receptor antagonist (IL-1ra) is a naturally occurring modulator of IL-1 that functions by competitively binding to IL-1 receptors without producing biologic effects. Interleukin-1 is believed to be a mediator involved in production of constitutional symptoms in patients with malignant lymphoma. Because we know of no study regarding IL-1ra expression in lymphomas, we tried to demonstrate the presence of IL-1ra in lymphomas using immunohistochemistry. DESIGN: Anti-IL-1ra monoclonal antibody was applied to paraffin sections of Hodgkin's disease and non-Hodgkin's lymphoma (NHL) with avidin-biotin complex method. RESULTS: Interleukin-1 receptor antagonist was found to be present primarily in benign reactive histiocytes in neoplastic tissue. Positivity for IL-1ra was found in 12 (67%) of 18 cases of Hodgkin's disease and 53 (29%) of 184 cases of NHL. The positivity rate varied in different subtypes of NHL. Three percent (1 in 30) of follicular small cleaved-cell lymphomas contained IL-1ra-expressing histiocytes, whereas 52% (17 of 33) of diffuse mixed-cell and 27% (12 of 44) of diffuse large-cell lymphomas contained IL-1ra-positive histiocytes. Nine of 13 (69%) cases of high-grade NHLs contained IL-1ra-expressing histiocytes. Among cases of NHL, the higher-grade NHL cases showed higher percentages of positivity. CONCLUSIONS: The findings further support the hypothesis that IL-1 may play a role in producing constitutional symptoms. PMID- 7887779 TI - Hyposplenic blood picture in systemic amyloidosis. Its absence is not a predictable sign for absence of splenic involvement. AB - We studied a total of 61 cases of systemic and senile amyloidosis to evaluate the significance of a "hyposplenic blood picture" (the presence of numerous Howell Jolly bodies) in these patients and to correlate its presence with the pattern and severity of the splenic involvement. To ascertain whether this peripheral blood picture is prevalent with a certain type of amyloidosis, we classified all cases by immunostaining with a panel of antibodies against AL amyloid (kappa and lambda light chains), serum amyloid-associated protein, prealbumin, beta-2 microglobulin, and amyloid p component. Based on immunostaining results, all cases were classified as AL (31 cases), AA (8 cases), or senile (prealbumin positive, 22 cases) amyloidosis. Howell-Jolly bodies were identified in six patients with amyloid L amyloidosis; of these, four cases had diffuse splenic cord involvement, one had a follicular pattern, and one had a vascular pattern. Only one of these patients had a typical hyposplenic blood picture. This patient had far-advanced diffuse splenic involvement. The remaining five patients had rare to few Howell-Jolly bodies. In addition, 12 other patients had diffuse splenic involvement with no Howell-Jolly bodies present. This study concludes that even when there is advanced diffuse replacement of splenic cords with amyloid on light microscopy, the "pitting" function of the spleen appears to be preserved in most cases. The absence of a hyposplenic blood picture cannot be equated with normal splenic cord histology in patients with systemic amyloidosis. PMID- 7887780 TI - Adrenal cortical carcinoma with adenosquamous differentiation. Report of a case with immunohistochemical and ultrastructural studies. AB - We report the case of an adrenal cortical carcinoma with glandular and squamous differentiation, demonstrated by light and electron microscopy as well as by immunohistochemical studies. The patient was a 63-year-old man presenting with a large adrenal mass and markedly increased 24-hour urine metanephrine, initially suggesting the diagnosis of pheochromocytoma. Upon histological examination of the surgically excised tumor, the presence of adenosquamous differentiation was most consistent with a metastasis to the adrenal gland. No other primary tumor was later found at autopsy, however. It thus becomes evident with this case that squamous and glandular differentiation can be observed in primary adrenocortical carcinomas, and therefore the conventional approach to the immunohistochemical and ultrastructural features of these tumors is challenged. This type of aberrant morphology in adrenocortical carcinomas makes the differentiation from a metastatic carcinoma particularly difficult for the surgical pathologist. Clinical correlation is absolutely necessary for an accurate diagnosis, and occasionally, as was the case with this patient, only with postmortem studies can another primary be ruled out with certainty. PMID- 7887781 TI - Curative resection of a well-differentiated papillary mesothelioma of the pericardium. AB - A 27-year-old woman presented with fatigue and dyspnea and was found to have a 2 x 4-cm mass in the pericardium, which was resected. Histologic examination demonstrated a well-differentiated papillary mesothelioma of the pericardium. Postoperatively, she received radiation therapy and had no evidence of recurrence 28 years later. It is extremely rare for this indolent variant of mesothelioma to arise in the pericardium. PMID- 7887783 TI - Lipoadenofibroma of the uterine corpus. Report of a new variant of adenofibroma (benign mullerian mixed tumor). AB - This report documents an uncommon case of uterine adenofibroma with a fatty component, for which the term lipoadenofibroma is proposed. Abdominal computed tomography and echography revealed a cystic submucosal lesion in the uterine corpus of a 67-year-old woman. Microscopically, the tumor was composed of benign epithelial cells of a proliferative-endometrial type and nonepithelial stromal cells. The latter mesenchymal elements contained scattered foci of mature adipose cells. The present case is considered to be a new variant of adenofibroma (benign mullerian mixed tumor) of the uterine corpus. PMID- 7887782 TI - Papillary cystic neoplasm of the pancreas with liver metastasis coexisting with thyroid papillary carcinoma. AB - BACKGROUND: Papillary cystic neoplasm of the pancreas is an uncommon neoplasm that usually appears to be benign or to have a very low potential for metastasis. We report a case of a patient with papillary and cystic neoplasm of the pancreas, which metastasized to the liver and concomitantly presented a stage I thyroid papillary carcinoma. CASE DESCRIPTION: The patient was a 38-year-old woman with a 12-year history of abdominal pain. She was first admitted to the hospital 3 years after symptoms began, and an exploratory laparotomy revealed a pancreatic cystic lesion that was diagnosed as a pancreatic pseudocyst, which drained by cystojejunosotomy. Nine years after onset, a stage I thyroid papillary carcinoma was excised. One-and-a-half years later, the patient was readmitted to the hospital for evaluation of a palpable abdominal mass. Abdominal computerized axial tomography disclosed a large pancreatic tumor and two nodular lesions of the liver. Papillary cystic neoplasm of the pancreas was diagnosed by cytologic, histologic, and ultrastructural studies of samples obtained directly from the pancreatic mass using fine-needle aspiration biopsy. The patient underwent palliative chemotherapy with mitomycin C, 4-epiadriamycin, and 5-fluorouracil. One year after this treatment began, a computerized axial tomography scan showed persistence of the pancreatic mass, with more prominent cystic spaces, increase in size and in number of the lesions in the liver, slight increase in the lesion of the right ovary, and a new lesion that also had solid and cystic areas in the spleen. CONCLUSION: The pathologic and clinical features of patients with papillary cystic neoplasm of the pancreas, based on tumoral extension, reveal localized tumors (88.2%), tumors with local infiltration or recurrence (6.2%), and tumors with metastasis at a distance (5.6%). Although strong similarities exist among the three groups, there are certain differences in age of presentation, previous clinical diagnosis of pseudocyst, and tumor location. PMID- 7887784 TI - Salivary trichomoniasis. A case report of infestation of a submaxillary gland by Trichomonas tenax. AB - A tumor was suspected after detection of an asymptomatic submaxillary swelling in an 85-year-old woman. Clinical, radiologic, and biologic investigations were fruitless. Transcutaneous needle aspiration revealed numerous trichomonads and led to the conclusion that a salivary duct was infested by Trichomonas tenax. The patient recovered following treatment with metronidazole, and there has been no recurrence after 2 years. This case sheds new light on the pathogenic properties of trichomonads. Peculiar features of this previously unreported location are discussed. Trichomonas tenax is often unrecognized by pathologists, and surely such cases are often misdiagnosed. PMID- 7887785 TI - Undifferentiated carcinoma of the gallbladder. Report of a case with immunohistochemical findings. AB - One case of undifferentiated carcinoma of the gallbladder was studied using an extensive immunohistochemical panel of antibodies. The biphasic differentiation of the tumor was highlighted by different immunoreactivity to antibodies against cytokeratins, vimentin, epithelial membrane antigen, and carcinoembryonic antigen of the adenocarcinomatous and mesenchymallike components, although the latter showed a faint positivity for CAM5.2 antibody, probably indicating an epithelial origin. Furthermore, the higher levels of expression of p53 protein and the faster growth rate in the pseudosarcomatous component suggest its more malignant phenotype. The relationship with "true" carcinosarcomas of the gallbladder and the histogenetic theories concerning these tumors are also discussed. PMID- 7887786 TI - Giant bilateral extra-adrenal myelolipoma. AB - We report a case of a giant bilateral extra-adrenal myelolipoma. To our knowledge this is only the second reported case of either giant or bilateral extra-adrenal myelolipoma and the first in which both features are present. The tumor is also notable for having areas of fibromyxoid degeneration histologically similar to those seen in low-grade fibromyxoid sarcomas. This feature, previously unreported, expands the differential diagnosis of extra-adrenal myelolipomas. PMID- 7887787 TI - Anal malignant melanoma and soft-tissue malignant fibrous histiocytoma in neurofibromatosis type 1. AB - A 48-year-old man with the nonfamilial form of neurofibromatosis type 1 (NF-1) developed a malignant fibrous histiocytoma in the deep soft tissue of the calf. Following excision and local radiotherapy, the tumor did not recur. At age 59, due to rectal bleeding, a polypoid malignant melanoma of the anal canal was detected and resected. One year later a local recurrence was removed, a pelvic mass was seen on computed tomography, and the patient died. The malignant melanoma was amelanotic and negative for HMB-45 (a melanoma-specific antibody), and the recurrent tumor showed areas of desmoplasia and prominent perineural and intraneural spread. The latter properties underscore the similarities of this melanoma to malignant peripheral nerve sheath tumor. In addition to neurofibroma and malignant schwannoma, NF-1 is associated with other neuroectodermal tumors, including brain tumors and pheochromocytoma. However, it is still controversial whether cutaneous malignant melanoma is more prevalent in NF-1 patients. Anorectal melanoma and malignant fibrous histiocytoma are exceedingly rare in NF 1. Second primary cancers are probably more frequent in NF-1 patients compared to the general population and may be related to alterations in the NF-1 gene. PMID- 7887788 TI - Autopsy training programs. To right a wrong. AB - Autopsy rates have decreased from a peak of 41.1% in 1964 to less than 5% in many hospitals today. This disaster has stimulated many symposia and articles on the values of the autopsy, the reasons for its fall, and possible remedies. The many benefits of the autopsy include quality assessment of clinical diagnoses; added knowledge about new diseases, environmental hazards, and genetic disorders; and evaluation of new technologies. The autopsy is also a powerful educational tool. The main reasons for its decline include fear of medical litigation and professional discreditation due to unexpected findings, the unsubstantiated notion that technologic advances have rendered the autopsy obsolete, cost-cutting pressures, and inadequate compensation for pathologists. This essay addresses a remedy for another major contributing problem: clinicians' frustration at poorly performed autopsies due to defective training of autopsy pathologists. Requirements for excellent autopsy training programs include an intensive review of anatomy applied to dissection methods, including sequences of dissection; direct supervision of early cases by a competent and responsible senior pathologist at the autopsy table, with full responsibility assigned to the trainee only after completion of this apprenticeship; review of all cases with clinical staff at regularly scheduled gross organ conferences; and a sustained commitment by department heads to make necessary programmatic changes to meet these standards. Pathologists must demonstrate pursuit of excellence in performance of the autopsy before other ambitious elements are sought for its revival. PMID- 7887789 TI - Pancreatic surgery. A paradigm for progress in the age of the bottom line. AB - The past few decades have seen great change in the capabilities of medical care. The next decade will emphasize great change in its delivery, driven mainly by the necessity of containing costs presently running at more than 13% of the gross national product. The current perception is that two of the principal causes of the excessive cost of medical care in the United States are the price of new technology and the fact that much of the care rendered is by specialists. In fact, most surgical care can be rendered by general surgeons, and the coming changes will revitalize the demand for and self-esteem of general surgeons. Managed care will recognize this by using general surgeons and keeping patients "down on the farm," a line drawn from the World War I era song entitled "How can you keep them down on the farm after they've seen Paree?" But some things are still unique to the medical equivalent of Paris, perhaps including more complex forms of treatment, the acquisition of knowledge, and teaching. The questions are: what should we decentralize and how do we discriminate what should remain decentralized in the community for economy, and what might be concentrated to good advantage in the centers? I would like to offer the pancreas as a paradigm in thinking about these issues. PMID- 7887790 TI - On the occasion of the 75th annual meeting of the New England Surgical Society. PMID- 7887791 TI - Gastric carcinoids. The Yale Experience. AB - OBJECTIVES: To document our experience with gastric carcinoids over the past decade and to identify lesion frequency and the existence of a relationship to low acid states. DESIGN: Retrospective case series. SETTING: Tertiary care referral center. PATIENTS: A consecutive sample of 16 patients with gastric carcinoids was evaluated over the last decade. Only two cases were recorded in the prior decade. Ages ranged from 30 to 93 years (mean, 65.9 years). There were eight men and eight women. Three patients were unavailable for follow-up. INTERVENTIONS: Therapy included total gastrectomy (n = 4), subtotal gastrectomy (n = 3), endoscopic polypectomy (n = 3), and endoscopic surveillance (n = 6). MAIN OUTCOME MEASURES: Pathobiological tumor characteristics and survival. RESULTS: All carcinoids were of gastric fundic origin. None of the patients exhibited the carcinoid syndrome. Chronic atrophic gastritis was the most frequently observed comorbid pathologic condition (63%). Half of the patients had multiple polypi. Mean follow-up was 4.7 years (n = 13). There were 10 survivors. The only related death occurred in a patient with a solitary tumor. CONCLUSIONS: Diagnosis of the complex and ill-defined entity of gastric carcinoid is increasing. This may be due to an increased awareness and increased upper gastrointestinal endoscopy rate rather than an increase in real incidence. Criteria for prediction of malignant progression are not available. Multiple gastric carcinoids associated with hypergastrinemia predominantly display nonaggressive behavior. Conservative gastric surgery may be appropriate therapy for such patients. PMID- 7887792 TI - Halofuginone, a specific collagen type I inhibitor, reduces anastomotic intimal hyperplasia. AB - OBJECTIVE: To determine if halofuginone hydrobromide, a specific type I collagen inhibitor, could prevent intimal hyperplasia at a vascular anastomosis. DESIGN: Intimal hyperplasia is characterized by smooth muscle cell proliferation and extracellular matrix accumulation. Halofuginone was used to block collagen production and smooth muscle cell proliferation in cell cultures and in a rabbit model of an end-to-end anastomosis of the right common carotid artery. Animals were fed a nontoxic dose of halofuginone. Eighteen rabbits were fed the inhibitor in a randomized blinded fashion and were examined after 4 weeks by harvesting the arteries after perfusion fixation at physiologic pressures. RESULTS: Halofuginone inhibited smooth muscle cell proliferation in vitro and had no effect on cell viability. Morphometric quantification verified that halofuginone treatment significantly attenuated anastomotic intimal thickness. CONCLUSION: Oral administration of halofuginone inhibits intimal hyperplasia at vascular anastomoses. Intimal hyperplasia inhibition by halofuginone may be a therapeutic option for preventing arterial stenosis in vascular surgery. PMID- 7887793 TI - Common bile duct exploration in the era of laparoscopic surgery. AB - OBJECTIVE: To review the treatment and outcome of patients with common bile duct (CBD) stones who underwent cholecystectomy. DESIGN: Prospective series of 700 consecutive laparoscopic cholecystectomies, with a mean follow-up of 22 months. SETTING: University-affiliated community hospital. PATIENTS: Eighty patients with documented CBD stones during a 42-month period (July 1990 to January 1994). INTERVENTIONS: Laparoscopic CBD exploration (LCBDE) was performed with either choledochotomy and T tube (n = 27) or transcystic duct choledochoscopy (n = 33). Open CBDE (OCBDE) (n = 16) and endoscopic sphincterotomy (n = 16) were also employed. MAIN OUTCOME MEASURES: Documented removal of CBD stones and procedure related complications. RESULTS: Laparoscopic CBDE was successful in 60 (94%) of 64 attempted cases. Mean operating time was 149 +/- 40 minutes and length of hospital stay was 2.8 +/- 2.1 days. Six complications (10%) were recorded, including three retained stones (5%). In 11 of 16 patients undergoing OCBDE, CBD stones were discovered with intraoperative cholangiography after conversion to laparotomy was needed for completion of the cholecystectomy. One OCBDE was planned in a patient with suppurative cholangitis. Preoperative endoscopic sphincterotomy (n = 11) was successful in four patients. Postoperative endoscopic sphincterotomy (n = 5) was successful in four patients. CONCLUSION: With a protocol of routine cholangiography, LCBDE, and selective use of OCBDE (when LCBDE is not possible), the reliance on a second procedure (endoscopic sphincterotomy) can be minimized. Laparoscopic CBDE, a technically demanding operation, is possible at the time of laparoscopic cholecystectomy in the majority of cases, with a low complication rate and a short length of hospital stay. PMID- 7887794 TI - A single-center experience with six-antigen-matched kidney transplants. AB - OBJECTIVES: To review our center's experience with the United Network of Organ Sharing six-antigen-matched (6-AgM) kidney program. Specifically, to determine whether recipients of 6-AgM cadaver kidney transplants have less perioperative and short-term (< 1 year) morbidity in comparison with living-related donor (LRD) recipients and a control group of immunologically less well-matched cadaver recipients. DESIGN: A retrospective review of all solitary kidney transplantations performed over a 24-month period, from 1992 to 1993. SETTING: A large urban tertiary care referral center with a long history of renal and extrarenal transplantation. PATIENTS: Adult patients receiving a solitary kidney transplant from either a cadaver or a living donor. MAIN OUTCOME MEASURES: Mortality, morbidity, and patient and graft survival. Other variables measured included rejection episodes, length of stay, readmissions, postoperative complications, waiting time, and delayed postoperative graft function. RESULTS: Recipients of 6-AgM kidney transplants were at higher risk than the control groups of cadaver and LRD recipients, with more retransplantations, higher sensitization, and more with diabetes. There were fewer rejection episodes in the 6-AgM group, and these were more steroid responsive. They had fewer hospital days (22.6 days) in the first year following transplantation, compared with the remaining cadaver group (28 days). The delayed postoperative graft function rate was also significantly lower than that of the cadaver control group. Graft and patient survival were excellent for all groups. Analysis of these factors showed similar results when comparing the LRD and 6-AgM groups and a marked improvement over the cadaver control group. CONCLUSIONS: Identical HLA matching for cadaver recipients provides superior results for graft and patient survival. There is much less perioperative morbidity in comparison with the less well-matched cadaver recipients. The effect of HLA matching is reflected in the perioperative courses of these patients, in addition to the long-term benefits of graft survival. Allograft survival is superior for this select group of cadaver recipients. The 6-AgM recipients behave similarly to LRD recipients in this cohort of patients. Our results would support the continued sharing of 6-AgM kidneys to optimize outcome and best use the limited resources available to the patients undergoing transplantation. PMID- 7887795 TI - Kidney transplantation in diabetic patients using cyclosporine. Five-year follow up. AB - OBJECTIVE: To review our center's experience with kidney transplantation in diabetic recipients; specifically, to compare long-term (5-year) patient and graft survival rates between diabetic and nondiabetic recipients overall and according to donor source using cyclosporine-based immunosuppression. DESIGN: A retrospective review of all kidney transplants performed over the 7-year period from 1987 to 1993. SETTING: A large urban tertiary care referral center with a long history of kidney transplantation and care of the diabetic patient. PATIENTS: All patients receiving a kidney transplant, either alone or simultaneously with a pancreas transplant, were reviewed. MAIN OUTCOME MEASURES: Actuarial patient and graft survival, serum creatinine levels, and causes of late graft loss. RESULTS: There was no significant difference in actuarial 5-year patient or kidney graft survival between diabetic and nondiabetic recipients overall or when analyzed by donor source. There was no significant difference in mean serum creatinine levels at 5 years between diabetic and nondiabetic recipients overall or between diabetic and nondiabetic cadaveric recipients. While chronic rejection was the major cause of late graft loss in nondiabetic recipients, death with a functioning graft, principally due to cardiovascular disease, was the major cause of graft loss in diabetic recipients. CONCLUSIONS: With cyclosporine-based immunosuppression, diabetic kidney transplant recipients have 5-year patient and graft survival rates and allograft function comparable to nondiabetic recipients. Given the high mortality of diabetic patients receiving dialysis, kidney transplantation is the treatment of choice for end-stage diabetic renal disease. PMID- 7887796 TI - Patient satisfaction following laparoscopic and open antireflux surgery. AB - OBJECTIVE: To compare laparoscopic (LNF) with open Nissen fundoplication (ONF) in terms of hospital charges, efficacy, and patient satisfaction. DESIGN: A prospective, nonrandomized study with a median follow-up of 370 days. SETTING: Two tertiary care university hospitals. PATIENTS: Eighty-six patients with complications of gastroesophageal reflux who had not had previous antireflux surgery were studied. Patients chose ONF or LNF following discussion with the surgeon; 12 underwent ONF and 74 underwent LNF, of whom eight required conversion to laparotomy. MAIN OUTCOME MEASURES: Hospital charges, disability, satisfaction, and side effects of fundoplication. RESULTS: Patients were demographically similar. Total charges (mean +/- SD) for LNF ($11,673 +/- $4723) were significantly less than for ONF ($18,394 +/- $17,264). Patients who underwent LNF returned to work sooner (10 +/- 3 days) than those who underwent ONF (28 +/- 1 days). Bloating, dysphagia, and recurrent heartburn occurred with equal frequency in both groups. Recurrent reflex occurred in four of 74 LNF patients and one of 12 ONF patients. Overall satisfaction scores were similar, irrespective of operative technique (LNF, 3.35 +/- 0.87; ONF, 3.50 +/- 0.94. CONCLUSIONS: Laparoscopic Nissen fundoplication is as effective as ONF in the treatment of complications of gastroesophageal reflux disease and appears to cost less and lead to faster recovery from surgery, but does not result in higher patient satisfaction than ONF. The most important factor in patient satisfaction is the abolition of preoperative symptoms rather than the type of operation. PMID- 7887797 TI - Standards for pancreatic resection in the 1990s. AB - OBJECTIVE: To describe the current indications and operative outcomes of pancreatic resection. DESIGN: Retrospective case series. SETTING: Referral practice in a university hospital. PATIENTS: Two hundred thirty-one consecutive patients undergoing pancreatoduodenectomy (PD), distal pancreatectomy (DP), or total pancreatectomy (TP) over a 44-month period. Their ages ranged from 16 to 85 years, with a mean of 54 years; 20% of the patients were 70 years old or older. MAIN OUTCOME MEASURES: Mortality, complications, and length of hospital stay. RESULTS: Operative mortality was 0.4% (one death following DP); there were no deaths in 142 PDs or in 18 TPs. The most common complication following PD was delayed gastric emptying. Pancreatic fistula occurred in 6.3% of PD and in 9.8% of DP patients. Overall, 58% of PD, 80% of DP, and 78% of TP patients had no complications. The mean +/- SD length of hospital stay was 15 +/- 7, 10 +/- 5, and 15 +/- 6 days for PD, DP, and TP, respectively. Reoperation for any cause was necessary in only 1.2% (3/231). The most frequent indication for PD was pancreatic cancer (36%) followed by chronic pancreatitis (26%); for DP it was chronic pancreatitis (28%) and cystic neoplasms (27%); and for TP, chronic pancreatitis (55%). Newer indications for pancreatic resection included mucinous ductal ectasia and intraductal papillary tumors (eight cases, 4%) and metastatic tumors (eight cases, 4%). CONCLUSIONS: Current indications for pancreatic resection have expanded. These procedures are associated with a low risk for death and postoperative complications when performed in a high-volume setting. PMID- 7887798 TI - A comparison of four severity-adjusted models to predict mortality after coronary artery bypass graft surgery. AB - OBJECTIVE: To assess the validity of four severity-adjusted models to predict mortality following coronary artery bypass graft surgery by using an independent surgical database. DESIGN: A prospective observational study wherein predicted mortality for each patient was obtained by using four different published severity-adjusted models. SETTING: A university-affiliated teaching community hospital. PATIENTS: Eight hundred sixty-eight consecutive patients who underwent coronary artery bypass graft surgery without accompanying valve or aneurysm repair during the period from 1991 to 1993. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Predicted mortality rates for each model were obtained by averaging individual patient predictions and were compared with actual morality rates. We assessed the accuracy of overall prediction for the total series, as well as compared individual patient predictions created by each model. The discrimination of models was assessed with receiver operating characteristic curves and the Hosmer-Lemeshow goodness-of-fit statistic. RESULTS: The observed crude mortality rate was 3.7%. The predicted mortality rate ranged from 2.8% to 9.2%, despite relatively good discrimination by the models (area under the receiver operating characteristic curve, 0.70 to 0.74). The individual patient mortality predicted by different models varied by as much as a ninefold difference. CONCLUSIONS: The currently used coronary artery bypass graft predictive models, although generally accurate, have significant shortcomings and should be used with caution. The predicted mortality rate following coronary artery bypass graft surgery varied by a factor of 3.3 from lowest to highest, making the choice of model a critical factor when assessing outcome. The use of these models for individual patient risk estimations is risky because of the marked discrepancies in individual predictions created by each model. PMID- 7887799 TI - Predictive accuracy of the TRISS survival statistic is improved by a modification that includes admission pH. AB - OBJECTIVE: To determine if pH measured at the time of hospital admission and corrected for PCO2 was an independent predictor of trauma survival. DESIGN: Phase 1 was a retrospective case-control analysis of 1708 patients, followed by multivariate multiple logistic regression analysis of a subset of 919 patients for whom the Revised Trauma Score (RTS), Injury Severity Score (ISS), and pH were available. Phase 2 was a prospective comparison of a mathematical model of survival derived in phase 1 (pH-TRISS) with the TRISS method in 508 of 1325 subsequently admitted trauma patients. SETTING: Urban level 1 trauma center. PATIENTS: All patients admitted with blunt or penetrating trauma during the study period. MAIN OUTCOME MEASURES: Survival vs mortality. RESULTS: In phase 1, factors significantly associated with mortality by t test and chi 2 analysis included the RTS, ISS< Glasgow Coma Scale, corrected pH (CpH), and sum of the head, chest, and abdominal components of the Abbreviated Injury Scale-85 (AIS85) (HCAISS) (for all, P < .0001). The TRISS statistic was also a significant predictor of survival (P < .004). Age, sex, and the extremity and soft tissue components of the AIS85 were not associated with mortality. In a multivariate analysis of the RTS, HCAISS, and CpH, all were significant predictors of mortality. Even when controlling for RTS and HCAISS, CpH remained a significant predictor of mortality (P < .008). In phase 2, when pH-TRISS was tested prospectively against TRISS in a new group of patients, the new statistic appeared to provide a more accurate prediction of survival. CONCLUSIONS: The arterial pH measurement obtained on hospital arrival and corrected for PCO2 is a significant independent predictor of survival and adds to the predictive accuracy of the TRISS survival statistic. Age, sex, and the extremity and soft tissue components of the AIS85 did not contribute to the accuracy of the TRISS statistic in this patient population. PMID- 7887800 TI - Biliary tract complications after liver transplantation. AB - OBJECTIVE: To assess the incidence, type, and treatment of biliary complications after orthotopic liver transplantation. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: One hundred ninety consecutive adults who underwent 220 orthotopic liver transplantations with biliary reconstruction between January 1, 1989, and December 31, 1993, with follow-up of all survivors to May 1994. MAIN OUTCOME MEASURES: Incidence, type, and treatment of biliary complications. RESULTS: Biliary complications were identified in 65 of the 190 patients who underwent biliary reconstruction (49 of 147 with choledochocholedochostomy and 16 of 43 with Roux-en-Y choledochojejunostomy). The group with complications who had choledochocholedochostomy had 32 biliary leaks (22 T-tube related), 11 strictures or obstructions, and six cases of choledocholithiasis. Twelve percent of choledochocholedochostomies were converted to choledochojejunostomies, while 26 of 49 biliary complications in patients who had choledochocholedochostomies were treated nonoperatively. Elective removal of T tubes resulted in biliary leak in 15 of 89 patients, treated nonoperatively in 12. Leaks (unrelated to scheduled removal of the tube) occurred earlier than strictures (choledochocholedochostomy, mean +/- SEM 25.6 +/- 5.8 vs 184.7 +/- 61.0 days; choledochojejunostomy, 13.4 +/- 4.4 vs 521.0 +/- 142.0 days) and were more often treated operatively (choledochocholedochostomy, 14 of 17 vs three of seven; choledochojejunostomy, four of five vs three of eight). Three deaths were associated with early biliary leaks, all in patients with preexisting multiorgan dysfunction. There was no significant difference in the incidence of biliary complications by type of reconstruction, year of transplantation, age, UNOS (United Network for Organ Sharing) status, preservation time, or indication for transplantation. CONCLUSIONS: Biliary complications are common after orthotopic liver transplantation but are rarely an isolated cause of death. Stenting of the choledochocholedochostomy or choledochojejunostomy anastomosis does not prevent strictures, and T tubes are associated with a high incidence of biliary leakage on removal. Nonoperative interventions have an increasing role in the treatment of biliary complications. PMID- 7887801 TI - Long-term morbidity following jejunoileal bypass. The continuing potential need for surgical reversal. AB - OBJECTIVE: To review the late sequelae of jejunoileal bypass (JIB) and the potential role of late surgical reversal in ameliorating morbidity and mortality following JIB. DESIGN: Patients who underwent JIB between 1965 and 1977 were contacted and pertinent health-event information was gathered. Early sequelae were defined as disorders occurring within the first 2 years after JIB; late sequelae were those occurring after 2 years. Health events occurring between 0 and 23 years after JIB were documented. SETTING: A private, tertiary referral center. PATIENTS: Patients underwent JIB for morbid obesity that had failed medical and/or psychiatric interventions. MAIN OUTCOME MEASURES: Body mass index (BMI) (weight kilograms divided by the square of the height in meters), diarrhea, electrolyte imbalance, acute, and chronic liver disease, renal disease, JIB reversal, reason for JIB reversal, death, and cause of death. RESULTS: A total of 453 morbidity obese patients underwent JIB. By 2 years following JIB, the mean (+/- SD) BMI dropped from 49.3 +/- 8.1 to 31.1 +/- 0.8 and remained at this level until year 15, after which weight gradually increased (BMI, 35.4 +/- 3.1). The most severe early complication was acute liver failure, which occurred in 7% of patients and caused seven deaths. At 15 years, the actuarial probability of the most common serious late complications related to JIB were renal disease (37%), with two deaths; diarrhea (29%); and liver disease (10%), with three deaths. One hundred thirty-eight patients (31%) had a bypass reversal. The most common indications for reversal were diarrhea and electrolyte disturbance (29%), renal disease (19%), and liver disease (17%). Fifty-six patients died more than 30 days after JIB: 64% before JIB reversal, 13% at the time of reversal, and 23% subsequently. CONCLUSIONS: Jejunoileal bypass is associated with progressive accrual of serious, sometimes life-threatening complications. Lifelong follow-up for early diagnosis and surgical reversal before life is threatened should reduce the morbidity and mortality associated with this procedure. PMID- 7887802 TI - Prevention of renal cortical ischemia during aortic clamping with prostaglandin E1. AB - OBJECTIVES: To investigate the effects of aortic clamping and prostaglandin E1 on systemic hemodynamics and renal cortical and medullary blood flow by means of continuous intraparenchymal laser Doppler fluorometry. DESIGN: Experimental animal study in a porcine model. With the animal under general anesthesia after hemodynamic monitoring was instituted, surgical exposure was obtained through a small left retroperitoneal incision. The kidney was left undisturbed. Intraparenchymal laser Doppler probes (0.44 mm in diameter) were inserted in the renal cortex and medulla. In the first group of six animals, systemic hemodynamic variables, urine output and renal cortical and medullary flow were measured at baseline after 60 minutes of equilibration, and after 15 minutes of aortic clamping and unclamping. Data are given as mean +/- SE. INTERVENTION: In another six animals, prostaglandin E1 (20-micrograms intravenous bolus given over 1 minute) was given before clamping, and the same variables were recorded. RESULTS: In the first group, aortic clamping caused no change in cardiac output or filling pressures. Cortical blood flow decreased from 40.4 +/- 3.7 to 33.3 +/- 2.7 mL/100 g per minute (P < .0004) after clamping, and to 27 +/- 2.3 mL/100 g per minute (P < .0001) after unclamping, and was associated with a decrease in urine output from 3.2 +/- 0.5 to 2 +/- 0.2 mL/min (P < .0013). Medullary flow remained the same at 9.2 +/- 0.8, 10 +/- 0.3, and 9.8 +/- 0.6 mL/100 g per minute, respectively. These adverse effects were prevented when prostaglandin E1 was given before clamping. There was an initial drop in blood pressure (100 +/- 4 to 89 +/- 5 mm Hg, P < .0004), but cardiac output (43.3 +/- 5.8 L/min) and filling pressures (6 +/- 1 mm Hg) were unchanged. Cortical flow was preserved during the entire period of clamping and unclamping (43.3 +/- 5.8 mL/100 g per minute). Medullary flow remained unchanged (10 +/- 0.8 mL/100 g per minute). Urine output increased from 2 +/- 0.3 to 3.4 +/- 0.6 mL/min (P < .006). CONCLUSIONS: In this animal model, infrarenal aortic clamping causes a significant decrease in renal cortical flow and urine output with no significant changes in filling pressures, cardiac output, or medullary blood flow. These adverse effects are prevented by pretreatment with prostaglandin E1, which prevents cortical ischemia and maintains brisk diuresis. PMID- 7887803 TI - Nonoperative management of splenic and hepatic trauma in the multiply injured pediatric and adolescent patient. AB - OBJECTIVE: To determine whether nonoperative management of splenic and hepatic injury in the multiply injured pediatric and adolescent patient is both safe and efficacious. DESIGN: Retrospective case series. SETTING: Level 1 trauma center. PATIENTS: All patients younger than 19 years old who suffered trauma to the spleen or liver between February 1978 and December 1991 (n = 103) were retrospectively identified by a trauma registry. These patients were divided into three groups: the group as a whole, those suffering multiple injuries, and those suffering either head injury or injury remote from the abdomen that required operative repair. MAIN OUTCOME MEASURES: Injury severity and outcome within each group of patients were compared based on whether the splenic or hepatic injury was managed operatively or nonoperatively. RESULTS: Mean Injury Severity Scores among the multiply injured patients were not different depending on whether the splenic or hepatic injury was managed nonoperatively or operatively. Except for a higher incidence of transfusion requirement among patients who were treated operatively, measures of morbidity among the multiply injured patients did not differ based on treatment. The success rates of nonoperative treatment among all patients, those with multiple injuries, and those with either head injury or remote injury that required surgery were 94%, 90%, and 86%, respectively. CONCLUSION: Nonoperative management of splenic and hepatic injury in multiply injured pediatric and adolescent patients, including those with head injury and injury remote from the abdomen that requires surgical intervention, is successful and is not associated with a prohibitive morbidity. PMID- 7887804 TI - [Genetic factor of type I allergy]. PMID- 7887805 TI - [A comparative evaluation of three commercially available peak flowmeters before and after being used 1000 times]. AB - The differences in values, accuracy, reproducibility and interdevice variability of three models of portable peak flowmeters (standard and low range of Assess, mini-Wright, Pulmo-Graph) before use and after they had been used 1000 times. A computerized standard flow generator was used to evaluate. Standard range; The three models showed differences in values before and after 100 uses of less than 3 percent at flow rates below 480 L/min. However, the used flowmeters, especially the Assess, showed higher values compared with the new ones at higher flow ranges. There was no significant difference in accuracy between the new and used mini-Wright and Pulmo-Graph models. The used Assess, howevers, showed higher values at higher ranges, thus demonstrating improved accuracy over the new ones. The reproducibilities of the three models deteriorated at high flow rates. The interdevice variability of the used Pulmo-Graph flowmeter was better than that the new one. No significant changes were observed in the mini-Wright, while the Assess showed deteriorated interdevice variability. Low range; The three models showed no significant differences in values, accuracy, reproducibility or interdevice variability before and after use. PMID- 7887806 TI - Sensitization to cockroach allergens of asthma patients in Japan. AB - To evaluate the role of allergens from Periplaneta fuliginosa, which is the most predominant cockroach species in homes in Tokyo areas, for asthma sensitization, we measured specific IgE antibodies to two cockroaches, P. fuliginosa and Blattella germanica, and to a mite, Dermatophagoides farinae, in 171 sera from children with asthma by Pharmacia's CAP system. We found that 16% of the sera had anti-P. fuliginosa IgE, whereas 9.9% had anti-B. germanica and 85% anti-D. farinae IgE. Further, we measured the levels of Per f I (Per a I equivalent) allergen in the house dust from living room, kitchen and bedding. We detected the allergen in eight of ten homes. The Per a I equivalent levels in kitchen were higher than in other sites, but they were much lower than Der I and Der II as Dermatophagoides allergens. PMID- 7887807 TI - Effect of inhaled cyclosporin A on the allergen-induced late asthmatic response and increased in airway hyperresponsiveness in a guinea pig model of asthma. AB - Oral administration of cyclosporin (CsA), a potent inhibitor of helper T cell function, prevents the allergen-induced late asthmatic response (LAR) and the increase in airway hyperresponsiveness (AH) seen in actively sensitized guinea pigs. The systemic administration of this agent in humans has been associated with serious side effect, therefore, the effects of inhaled CsA were therefore examined in guinea pigs that were actively sensitized by repeated exposure to nebulized ovalbumin. Respiratory resistance (Rrs) of the animals was measured by an oscillation method and the extent of AH was inferred from the inhaled concentration of histamine required to increase Rrs by 200%. The magnitude of ovalbumin-induced immediate bronchoconstriction after sensitization was similar in CsA-treated and nontreated control animals. However, a LAR was observed in 4/5 control animals but in 0/5 CsA-treated animals. The increase in AH observed 24 hours after antigen exposure in control animals was significantly inhibited by prior CsA inhalation. Significant CsA concentrations were detected by radioimmunoassay in the lungs of CsA-treated animals. Thus, inhaled CsA should be further investigated because it may be useful treating asthma while avoiding side effects. PMID- 7887808 TI - [Inhibitory effect of AS-35. a novel antiallergic drug, on chemical mediator release from human eosinophils]. AB - To determine whether AS-35, a new antiallergic drug, inhibits the activation of eosinophils, we examined the effect of AS-35 on the release of leukotriene C4 (LTC4) and eosinophil peroxidase (EPO) from human eosinophils. Calcium ionophore A23187 caused both LTC4 and EPO release from human eosinophils. AS-35 (1 x 10(-5) M) inhibited A23187-induced LTC4 release from the eosinophils with 56% inhibition. AS-35 (1 x 10(-6) to 1 x 10(-5) M) also inhibited A23187-induced EPO release from the eosinophils in a dose-dependent fashion with 79% inhibition at 1 x 10(-5) M. We concluded that AS-35 prevents the activation of human eosinophils to inhibit LTC4 and EPO release. These results suggest that AS-35 might be useful in controlling allergic diseases by inhibiting eosinophil activation. PMID- 7887809 TI - [Inhibitory effects of exogenous eicosapentaenoic acid on generation of leukotriene C4 and leukotriene B4 by human leukocytes stimulated with calcium ionophore]. AB - Effects of exogenous eicosapentaenoic acid (EPA) and arachiodonic acid (AA) on generation of leukotriences C4, C5, B4 and B5 were assessed in human leukocytes stimulated with calcium ionophore A23187. Human leukocytes were obtained from healthy volunteers using the dextran sedimentation of peripheral blood and stimulated with 1 microgram/ml calcium ionophore A23187 in the absence or presence of EPA (1-30 micrograms/ml) and/or AA (1-30 micrograms/ml). Leukotriences from leukocytes samples were separated and quantitated by reverse phase high performance liquid chromatography. Mean generation of LTC4 in the absence of fatty acid was 78.2 +/- 25.4 ng/10(7) cells (Mean +/- SD, n = 6). In the presence of EPA, the generation of LTC4 increased a little but significant (p < 0.05) to 85.3 +/- 24.2 ng/10(7) cells at low dose (1 microgram/ml) of EPA, and then decreased to 39.7 +/- 23.4 ng/10(7) cells at high dose (30 micrograms/ml) of EPA (p < 0.05). LTB4 generation was 213.2 +/- 38.0 ng/10(7) cells without fatty acids, and decreased to 174.0 +/- 48.0 ng/10(7) cells at 30 micrograms/ml EPA (p < 0.05). LTC5 and LTB5 production were detectable at 1 microgram/ml EPA and reached to maximum at 10 micrograms/ml EPA with 21.9 +/- 15.6 ng/10(7) cells and 21.8 +/- 7.1 ng/10(7) cells, respectively. Total LTC (LTC4 + LTC5) generation with high dose of EPA (57.2 +/- 28.0 ng/10(7) cells) decreased significantly compared with that in the absence of fatty acids (78.2 +/- 25.4 ng/10(7) cells). At 10 micrograms/ml of AA, both LTC4 and LTB4 generation significantly increased to 114.2 +/- 5.3% and 129.0 +/- 9.5% of control, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887810 TI - [Local characteristic of allergic diseases: adult asthma in the central area of Tokyo]. AB - In order to know the characteristic of urban asthma, were analyzed patient records in our clinic located in the central area of Tokyo. Eighty four adult patients who were living in walking distance with asthma started in this area, visited our clinic in October 1991. Among them 57 (68%) were atopic type. 13 (15%) mixed type, and 14 (17%) infectious type. Even among 25 patients with late onset asthma over 40 year of age, there were 8 atopic type and 5 mixed type, and 11 were positive against house dust by RAST and/or skin test. Atopic type seems to be unusually frequent in urban asthma. It reminds us of the fact that Japanese cedar pollinosis is more frequent in urban area than the mountain area with much more cedar trees. These might suggest important points to be studied, not only the adjuvant effect but also some accelerating effect for allergic diseases in the urban environment. PMID- 7887811 TI - [Characterization of infiltrating mononuclear cells in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis (EAE)]. AB - Mononuclear cells (MNCs) infiltrating in spinal cords (SCs) of Lewis rats with EAE were isolated in order to permit flow cytometric (FCM) analysis of these cell populations, using monoclonal antibody to T cell, CD4, CD8. MHC class II antigen (Ia), intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function associated antigen-1 (LFA-1). The number of MNCs isolated from SC varied from 5 to 620 x 10(4). They were increased and reached a peak on day 2 post clinical onset, and subsequently declined through the clinical course. The increase of infiltrating cells in SC paralleled the severity of the disease development. The surface phenotypes of MNCs from rats on the day of clinical onset were determined by flow cytometry. The phenotypes found in these rats were as follows: T cells (70.3%); CD4 + (58.3%); CD8 + (40.3%); Ia (51.9%); ICAM-1 (62.6%); LFA-1 (75.8%). These findings suggest that high proportion of ICMA-1 and LFA-1 expression may be important in antigen presentation in the inflammatory lesions of SC and in promoting lymphocyte extravasation across the blood-brain barrier during the disease. The approach we employed offered more sophisticated and quantitative analysis of CNS inflammatory cells, which is unobtainable by tissue section staining. PMID- 7887812 TI - Antigenic relationship between the house dust mite Dermatophagoides farinae and the predacious mite Phytoseiulus persimilis. AB - We have examined the antigenic relationship between the house dust mite Dermatophagoides farinae and the predacious mite Phytoseiulus persimilis. Immunoblotting analysis demonstrated that there was a very weak antigenic cross reactivity between these different suborder of mites but that this cross reactivity was not attributed to D. farinaes major allergen's, Der fI and Der fII. These results suggest that P. persimilis might scarcely provoke allergic symptoms in patients sensitized to house dust mites. PMID- 7887813 TI - The challenges of being a mother and an independent midwife. PMID- 7887814 TI - Discussion paper on homebirth. PMID- 7887815 TI - Midwifery competency standards. PMID- 7887816 TI - Independent midwifery. PMID- 7887817 TI - Becoming an independent homebirth midwife. PMID- 7887819 TI - The accreditation of independently practising midwives: a brief history. PMID- 7887818 TI - Midwifery profile. PMID- 7887820 TI - The recognition of traditional midwives. AB - This article explores the reasons why Australian traditional midwives need to be recognised by their registered sisterhood. This issue is of particular significance as NSW midwives gear themselves for a campaign to redress the 1991 changes to the NSW Nurses Act. This Act threatens in a variety of ways to denigrate the future of midwifery as an autonomous profession. Do we leave the plight of the traditional midwife to feminist groups to raise and address, or do we work in harmony and with a responsibility to the less recognised, to achieve a profession that is responsive to all women's needs, whatever their race, locale and class? PMID- 7887821 TI - Issues involved in setting up a private practice. AB - Jen Byrne and Vicki Bruce conduct Parenting Education for expectant parents, a private practice of childbirth education in Adelaide. How the practice evolved and what goals were set, the time lines, commitment to the cause and taking risks to achieve results all required careful thought. There were barriers too, in setting up this practice. This paper discusses the particular issues involved in setting up a private practice in childbirth education. Midwives and nurses are new to the area of private practice and our education has not prepared us for this expansion of our role. Issues such as the legal aspects, financial survival, professional support and marketing are discussed. PMID- 7887822 TI - Computer control of cardiac prostheses: is it really necessary? PMID- 7887823 TI - Filling a dialysis circuit with albumin does not prevent platelet activation during hemodialysis: in vivo study. AB - The aim of our prospective clinical study was to evaluate whether filling a dialysis circuit with albumin before hemodialysis (HD) can prevent platelet activation during the procedure. Eight patients with chronic HD participated in the study, each dialyzed first with albumin and a week later without it. All other parameters of the HD procedure were unchanged (cellulose acetate hollow fiber dialyzer, blood flow of 300 ml/min, and low dose heparin). Before HD with albumin, 6.7% human albumin in saline was recirculated in the dialysis circuit for 10 min at a flow rate of 100 ml/min, and infused into the patient. We found a significant increase in the beta-thromboglobulin levels during both procedures. We found no difference in plasma coagulation system activation measured by fibrinopeptide A concentration. Neither was there any difference in the macroscopic antithrombotic activity assessed at the end of HD by measuring the volume of clots in the arterial and venous bubble trap and by counting the number of clotted fibers in the dialyzer. It seemed that filling the dialysis circuit, which had a cellulose acetate dialyzer, with human albumin did not improve its thrombogenicity. PMID- 7887824 TI - Acute symptoms during and between hemodialysis: the relative role of speed, duration, and biocompatibility of dialysis. AB - The relationship between hemodialysis (HD) symptoms and dialyzer membrane composition and area, blood-flow, treatment duration, urea removal, ultrafiltration volume, leukocyte activation, and complement generation (C3a) was studied in 20 patients undergoing 234 HD treatments by 12 different modes in random order using Cuprophan, hemophane, or polyamide membranes with small or large membrane areas with high Qb (400 ml/min) and short duration (2 h) or low Qb (200 ml/min) and long duration (4 h). Fewer symptoms occurred during the 2-h HD at high Qb than during the 4-h HD with low Qb (19% vs. 32%, p = 0.0351). No differences were observed between different dialyzer membranes or areas. More intradialytic symptoms occurred when urea elimination was high than it was low (p = 0.0044). Leukocyte activation (leukocyte drop) after 15 min of dialysis and complement generation did not influence symptom incidence. Blood pressure changes were mainly influenced by ultrafiltration volume (p < 0.001). Symptoms between dialyses were determined by urea removal and ultrafiltration. Membrane, area, or Qb were of no importance. Thus, duration of dialysis, urea removal, and demand for ultrafiltration, but not membrane composition, area, or biocompatability, are important for the development of HD-related symptoms. PMID- 7887825 TI - Review of immunomodulation by photopheresis: treatment of cutaneous T-cell lymphoma, autoimmune disease, and allograft rejection. AB - Photopheresis is an apheresis-based therapy that is currently available at approximately 70 medical centers worldwide. Recent evidence indicates that extracorporeal photopheresis can significantly prolong life as well as induce a 60-75% response rate among individuals with advanced cutaneous T-cell lymphoma (CTCL). Moreover, a 10-15% cure rate, in response to photopheresis alone, or in combination with interferon-alpha, has been obtained at our institution. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. Southern blot analysis of peripheral blood specimens has also confirmed the indefinite disappearance of the malignant T-cell clone from the blood of patients with complete responses. Current immunological data obtained from in vitro human studies and from animal models suggest that the basis for the responses of CTCL patients are related to activation of treated macrophages resulting in release of cytokines, including substantial levels of tumor necrosis factor alpha (TNF-alpha), and perhaps, to the induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes. In addition to the treatment of CTCL, a potential role for photopheresis in the therapy of autoimmune disease has been suggested by recent pilot studies of pemphigus vulgaris, rheumatoid arthritis, and systemic lupus erythematosus. Furthermore, a randomized, single-blinded trial involving 79 patients with early onset, aggressive systemic sclerosis suggested that photopheresis could benefically affect the course of the cutaneous thickening in this form of the disease. Lastly, two independent pilot studies of cardiac transplantation have indicated that photopheresis can reverse acute cardiac allograft rejection and potentially suppress ongoing chronic rejection. Randomized, controlled trials for these new indications for photopheresis therapy are currently in the early stages of implementation. PMID- 7887826 TI - Complement activation by alginate-polylysine microcapsules used for islet transplantation. AB - A foreign body reaction is frequently observed around implanted microcapsules of alginate-polylysine. Since complement activation can play a role in this reaction, we checked in vitro the ability of empty alginate-polylysine microcapsules to activate complement. Human serum was incubated with microcapsules, and complement activation was evaluated by two methods: the complement hemolytic activity (CH50) and the assay of the C3adesArg fragment. The occurrence of complement activation in the presence of microcapsules was suggested both by a CH50 decrease and by high C3adesArg levels despite C3adesArg adsorption to the capsule membrane. Capsule membrane protection against the cytotoxic effects of complement was also tested. No hemolysis occurred when microencapsulated sensitized sheep erythrocytes were incubated with activated complement. In conclusion, the microcapsule membrane can protect cells against activated complement fragments. Nevertheless, alginate-polylysine microcapsules do activate complement, and this effect must be considered for its use as an implant. PMID- 7887827 TI - Biocompatibility of heparin-coated membrane oxygenator during cardiopulmonary bypass. AB - The biocompatibility of the cardiopulmonary bypass (CPB) circuit, in which an oxygenator is solely heparinized, was assessed by systemic inflammatory reactions as an indicator during CPB. Fourteen patients, 11 males and 3 females, underwent coronary artery bypass surgery and were randomly divided into 2 groups of 7 patients each. For the heparin-coated oxygenator group (Group H), a heparin coated membrane oxygenator was used in the CPB circuit, and in the control (Group C) an uncoated membrane oxygenator was employed. Systemic inflammatory reactions, such as platelet activation, prostaglandin production, complement activation, and activated granulocyte released substance, were measured prior to, during, and 6 h after CPB. The number of platelets decreased after protamine administration in both groups (14.5 +/- 4.7 x 10(4)/microliters in Group H and 13.8 +/- 8.7 x 10(4)/microliters in Group C) and returned to baseline levels in Group H while it remained decreased in Group C at 6 h after CPB. The platelet factor 4 level was significantly lower in Group H (181 +/- 40 ng/ml) than in Group C (297 +/- 131 ng/ml) after protamine administration. Thromboxane-B2 (TXB2) rose during CPB in both groups; however, there were significantly different levels of TXB2 between the 2 groups at 60 min after CPB (293 +/- 258 pg/ml in Group H versus 408 +/- 120 pg/ml in Group C) and after protamine administration (259 +/- 122 pg/ml in Group H versus 709 +/- 418 pg/ml in Group C). Plasma concentrations of granulocyte elastase were significantly lower in Group H at 30, 60 and 90 min, immediately after, and post-CPB than those of Group C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887828 TI - Development of a compact, highly efficient, totally implantable motor-driven assist pump system. AB - We have developed a compact, highly efficient, totally implantable assist pump system, which consists of a motor-driven assist pump and a transcutaneous energy and optical information transmission system. The motor-driven assist pump consists of a.d.c. brushless motor and a specially designed miniature ball screw. A magnetic coupling mechanism between the blood pump and an actuator provides active blood filling via mild suction force. The controller consists of a PID follow-up controller using an 8-bit one-chip microcomputer. The volume of the pump is 350 ml, and its controller is 210 ml. Pump outflow of 5.8 L/min was obtained against a mean after-load of 100 mm Hg. The pump showed a high efficiency rate and good durability. An efficiency rate of 19-21% (pump output/motor input) was obtained during 87 days of continuous pumping. No mechanical trouble occurred for an accumulated period of 6 months. PMID- 7887829 TI - Experimental assessment of right ventricular function in normal pigs with a left ventricular assist device. AB - Right ventricular (RV) failure during the use of a left ventricular assist device (LVAD) is the leading cause of death in circulatory support patients. Previous work, both experimentally and clinically, has shown the difficulties in predicting the behavior of the right ventricle at the start of LVAD. An experimental study has been designed to evaluate RV functional changes during LVAD and its relation to preload changes. The model used adult mongrel pigs (n = 10). Right ventricular functional parameters were measured with a thermodilution RV ejection fraction catheter. The left ventricle was supported by a Nippon Zeon blood pump. Two groups were studied, the first one was the LVAD-off group (n = 5) and the other was the LVAD-on group (n = 5) which was supported by LVAD at maximum flow. Change of cardiac output, mean pulmonary artery pressure (PAP), RV stroke work, and RV ejection fraction in both groups were not significantly different. However, the relationship between right ventricular end-diastolic pressure (RV-EDP) and right ventricular stroke volume (RVSV) was significantly changed at a high level of RV-EDP. When RV-EDP was over 6.5 mm Hg in the LVAD-off group, RVSV decreased to 52.3 +/- 11.5 ml while in the LVAD-on group, RVSV increased to 97.2 +/- 22.0 ml. The change in PAP in the LVAD-on group was lower than in the LVAD-off group. We conclude that, at the volume overload state, LVAD can reduce the afterload of the right ventricle and maintain Frank-Starling's effect, thus having a beneficial effect on right ventricular performance. PMID- 7887830 TI - Flow pattern analysis of the Baylor total artificial heart. AB - To obtain an optimal design of the left blood chamber of the total artificial heart (TAH), flow visualization studies were performed. Information on velocities in critical areas of the left chamber was gathered using sectional pulsed laser light. The flow patterns on the entire pumping duration were photographed frame by frame. The inflow port, the opposite of the inflow and outflow of the pump (bottom area), and the diaphragm/housing junction were the focal areas. The pump conditions, such as chamber pressure, preload and afterload pressure, pumping rate and roller screw, and displacement were recorded. Major stagnations and a low washout effect were observed in the bottom region. The closing of the inflow valve was irregular. In order to solve this problem, the inflow valve angle was changed 20 degrees. A comparison study showed a better valve closing characteristic, and no stagnation areas were observed with this new valve angle. Various velocity profiles confirmed the results. The valve closing characteristics is described in relationship to back flow. PMID- 7887831 TI - Impact of ultrafiltration on back-diffusion in hemodialyzer. AB - Ultrafiltration of water from blood to dialysate decreases the rate of back diffusion of solutes from dialysate to blood. Therefore, back-clearance (bK) of hemodialyzers may be expressed as bK = bK0--bTrQu, where bK0 is the diffusive back-clearance, bTr is the "back-"transmittance coefficient, and Qu is the net ultrafiltration rate. A formula for bK was derived from the one-dimensional theory of hemodialyzer, and bTr was described as a function of bK0 and the Staverman reflection coefficient. The transport parameters, bK0 and bTr, for creatinine and vitamin B12 were measured in two types of hemodialyzers with negligible back-filtration, using water solutions, and compared with the transport parameters, K0 and Tr, for the case of both diffusion and ultrafiltration from blood to dialysate. bK0 was in general equal to K0. bTr was not different from Tr for creatinine whereas bTr was lower than Tr for vitamin B12. Experimental values of bTr for vitamin B12 were in general agreement with theoretical predictions. However, experimental values of bTr for creatinine were lower than predicted values. We conclude that the impact of ultrafiltration on back-clearance for slowly diffusing solutes is weaker than on their clearance. PMID- 7887832 TI - Biocompatibility of a heparin-bonded membrane oxygenator (Carmeda MAXIMA) during the first 90 minutes of cardiopulmonary bypass: clinical comparison with the conventional system. AB - We clinically compared a heparin-bonded Carmeda MAXIMA membrane oxygenator to a nonheparin-bonded MAXIMA in 20 patients undergoing coronary artery bypass grafting or valve replacement. Reductions of fibrinogen, factor XII, and high molecular weight kininogen were greater in the MAXIMA group. Serum C3a and free hemoglobin were lower in the Carmeda group. The level of C4a, though remarkably lower than that of C3a, was higher in the Carmeda group then in the MAXIMA group. Both oxygenators performed well in terms of blood gas exchange. We conclude that the heparin-bonded Carmeda oxygenator offers superior biocompatibility during cardiopulmonary bypass. PMID- 7887833 TI - Social, ethical, and economic aspects of the treatment for end-stage renal failure in Spain. PMID- 7887834 TI - Diclofenac and its effect on corneal sensation. PMID- 7887835 TI - An illuminating laser probe for vitreoretinal surgery. PMID- 7887836 TI - Pseudomonas endophthalmitis presenting as subacute inflammation. PMID- 7887837 TI - Surgery for ischemic optic neuropathy. PMID- 7887838 TI - The galactosemic dog. A valid model for both early and late stages of diabetic retinopathy. PMID- 7887839 TI - Astigmatism reduction clinical trial: a multicenter prospective evaluation of the predictability of arcuate keratotomy. Evaluation of surgical nomogram predictability. ARC-T Study Group. AB - OBJECTIVE: To determine the accuracy of the Lindstrom surgical nomogram for astigmatism. DESIGN: A prospective multicenter study. PATIENTS: One hundred sixty eyes of 95 patients underwent astigmatic keratotomy in eight centers by nine surgeons. Inclusion criteria for the study included age of at least 18 years with 1 to 6 diopters (D) of naturally occurring corneal astigmatism and less than 1 D of lenticular astigmatism. INTERVENTIONS: A standardized astigmatic keratotomy surgical technique was performed on each eye. Surgical measurements were determined using the Lindstrom surgical nomogram for astigmatism. MAIN OUTCOME MEASURE: The Holladay, Cravy, Koch vector analysis method was used to determine the change in refractive cylinder results. Refractive changes also are presented without vector analysis merely using the absolute change in refractive cylinder and axis. RESULTS: Multiple regression analysis was used to develop a mathematical model determining the factors predictive of the change in refractive cylinder. The significant predictors for the amount of astigmatic correction achieved were, in order of decreasing importance, the following: number of incisions (R2 = 30%), incision length (R2 = 16%), age (R2 = 8%), and gender (R2 = 2%). CONCLUSIONS: Astigmatism is a two-dimensional measurement of both quantity and direction that is most appropriately analyzed with vector analysis. The original Lindstrom surgical nomogram for arcuate keratotomy used in this study is still quite useful although it tended to underpredict results for many patients, especially those having two incisional surgeries. Some older subjects having minimal surgery achieved greater correction than predicted by the original nomogram. The most important factors predictive of greater astigmatic keratotomy surgical effect are incision number, incision length, older age, and male gender. PMID- 7887840 TI - Aqueous flow in open-angle glaucoma. AB - OBJECTIVES: To measure aqueous dynamic variables in patients with open-angle glaucoma when their ocular hypotensive treatment was withdrawn and to determine if the circadian rhythm of the aqueous humor flow was present in open-angle glaucoma. METHODS: We studied 20 patients with open-angle glaucoma, and a group of 20 healthy subjects served as controls. Aqueous humor flow was measured by clearance of topically applied fluorescein with a fluorophotometer, tonography was used to measure outflow facility, and applanation tonometry was used to measure the intraocular pressure. RESULTS: We did not find any statistically significant difference when comparing aqueous flow during the daytime in subjects with open-angle glaucoma with that in controls. However, we did measure a higher aqueous flow at night in the group with open-angle glaucoma, compared with the normal group. The circadian rhythm of aqueous humor flow was present in the subjects with glaucoma. CONCLUSIONS: Aqueous flow is not suppressed in glaucomatous eyes that are not undergoing treatment. Rather, the flow is slightly higher at night during sleep compared with the flow in normal sleeping subjects, but not high enough to have a clinically significant effect on intraocular pressure. PMID- 7887841 TI - The efficacy of apraclonidine as an adjunct to timolol therapy. Apraclonidine Adjunctive Therapy Study Group. AB - OBJECTIVE: To compare the intraocular pressure (IOP) lowering efficacy of 0.5% and 1.0% apraclonidine hydrochloride when used adjunctively with 0.5% timolol maleate in 129 patients. DESIGN: A multicenter, randomized, double-masked clinical trial. Adult patients of either sex diagnosed as having either open angle glaucoma or ocular hypertension were enrolled in the study. Patients using only 0.5% timolol maleate twice daily for at least 4 weeks and who had 8 AM IOPs of at least 22 mm Hg and no greater than 30 mm Hg 12 hours after dosing were eligible for the study. After 8 AM baseline IOPs were obtained while patients were taking timolol only, they were then randomized to receive either 0.5% or 1.0% apraclonidine twice daily in addition to their timolol. Intraocular pressures were measured at 8 AM (before morning dosing) and at 11 AM (3 hours after dosing) on days 14 and 90 and at 8 AM only on day 45. RESULTS: Both concentrations of apraclonidine produced significant IOP reductions from baseline at all visits (P < .001). At 8 AM, after the nighttime dose, the additional mean IOP reduction from the timolol baseline ranged from 2.5 to 3.3 mm Hg (10.3% to 13.6% reduction, respectively). At 11 AM, 3 hours after the morning dose, the additional IOP reduction from the timolol baseline ranged from 4.7 to 5.2 mm Hg (20.0% to 21.7%, respectively). No difference in IOP reduction was observed between the 0.5% and 1.0% apraclonidine concentrations and no loss of IOP efficacy was observed for either concentration for the duration of the study. Sensitivity to 0.5% and 1.0% apraclonidine was observed in nine (13.8%) and 13 (20.3%) patients, respectively. Overall, therapy was discontinued owing to ocular or nonocular side effects with 0.5% and 1.0% apraclonidine in 14 (21.5%) and 16 (25%) patients, respectively. CONCLUSIONS: We believe that 0.5% apraclonidine is equally effective as 1.0% apraclonidine when used twice daily as the first adjunctive drug to timolol. The drug effect is maintained for at least 90 days. PMID- 7887842 TI - Clinical experience with the long-term use of 1% apraclonidine. Incidence of allergic reactions. AB - OBJECTIVE: To identify the incidence and characteristics of allergic reactions associated with the long-term use of 1% apraclonidine hydrochloride. METHODS: We undertook a retrospective analysis of 64 patients receiving long-term 1% apraclonidine therapy at the University of California-San Francisco Glaucoma Service. Patients were excluded if the duration of treatment was less than 2 weeks. Demographic data, initial intraocular pressure response, and incidence and characteristics of allergic reactions were obtained through chart review. Student's t test and chi 2 analysis were used to analyze the demographic data, and Kaplan-Meier survival analysis was used to estimate the long-term incidence of local reactions. RESULTS: Sixty-four patients met the criteria for the study. Of these, 31 (48%) developed an allergic reaction (responders) that led to discontinuation of treatment with the medication, with a mean latency of 4.7 months. Mean follow-up was 13.3 months. Patients free of local reactions (nonresponders) for at least 10 months were able to successfully continue apraclonidine use. Responders tended to be older and female. CONCLUSIONS: Our data are specific for the 1% preparation; however, physicians prescribing apraclonidine on a long-term basis should be aware of possible allergic reactions. A substantial percentage of patients developed this side effect, but most tolerated the medication for up to 4 months, and those without a local reaction after 10 months appeared to be able to continue apraclonidine use indefinitely. This allergic reaction is likely related to the adrenergic agent itself, and not to preservatives. PMID- 7887843 TI - Acute posterior multifocal placoid pigment epitheliopathy after hepatitis B vaccine. AB - OBJECTIVE: To report two cases of acute posterior multifocal placoid pigment epitheliopathy after immunization with a recombinant hepatitis B virus vaccine. DESIGN: Case reports. RESULTS: Two patients had development of visual loss 3 days to 2 weeks after the booster administration of 20 micrograms of recombinant hepatitis B virus surface antigen (Engerix-B). In both cases, fundus examination, fluorescein angiograms, and the course of the disease were typical of acute posterior multifocal placoid pigment epitheliopathy. In case 1, 1 week after immunization, the leukocyte count was 10.3 X 10(9)/L with 24% polynuclear eosinophils (2.47 X 10(9)/L); in case 2, blood cell counts were normal. CONCLUSION: Hepatitis B virus immunization may be a risk factor for acute posterior multifocal placoid pigment epitheliopathy. Molecular mimicry between a retinal pigment epithelium protein and hepatitis B surface antigen could play a role. These cases suggest an immune-mediated retinal pigment epithelium disruption or choroidal vascular occlusions triggered by hepatitis B surface antigen. PMID- 7887844 TI - Retinal hemorrhage as a consequence of epidural steroid injection. AB - OBJECTIVE: To report that retinal hemorrhage is an important but uncommon complication of epidural steroid injection, a procedure frequently employed to alleviate chronic back pain. DESIGN: Patients who complained of visual field defects or blurred vision after receiving the injection received complete eye examinations, including fundus photography and fluorescein angiography. They were then followed up as their clinical situation dictated. SETTING: Patients were examined in an outpatient setting in our offices. PATIENTS: Between 1989 and 1992, five eyes of four female patients ranging in age from 35 to 81 years were evaluated and followed up. RESULTS: Examination and photographic documentation showed that these eyes had retinal hemorrhages, often distributed in a petaloid pattern, which resulted in transient loss of vision from 6 weeks to 6 months. CONCLUSIONS: Retinal hemorrhage is an uncommon but significant and previously unemphasized complication of epidural steroid injection for chronic back pain. This procedure should be carefully considered, particularly in one-eyed patients and those with bleeding problems, and patients should be fully informed that this can happen despite appropriate care and technique. PMID- 7887845 TI - Transpupillary thermotherapy in choroidal melanomas. AB - OBJECTIVE: To determine safety and efficacy of transpupillary thermotherapy (TTT) as a new treatment for choroidal melanoma. METHODS AND PATIENTS: To perform TTT, diode laser energy at 810 nm was used with a beam diameter of 1.5 to 4.5 mm for a 1-minute exposure. All 12 patients had choroidal melanoma. Six had had insufficient response to ruthenium 106 (106Ru) brachytherapy. Three patients with tumors more than 5 mm in height were treated simultaneously with 106Ru and TTT. Three patients with juxtapapillary or macular tumors were treated by TTT only. RESULTS: All but one tumor exhibited a reduction of tumor height in a follow-up period of 3 to 14 months. Side effects were minimal. Severe visual loss occurred in two patients due to radiation retinopathy, in two patients whose foveas were included in the TTT area, and in one patient resulting from a serous retinal detachment that extended over the posterior pole. CONCLUSIONS: Treatment with TTT may be useful as a complementary modality to brachytherapy. A longer follow-up period is required for final evaluation. PMID- 7887846 TI - Optical coherence tomography of the human retina. AB - OBJECTIVE: To demonstrate optical coherence tomography for high-resolution, noninvasive imaging of the human retina. Optical coherence tomography is a new imaging technique analogous to ultrasound B scan that can provide cross-sectional images of the retina with micrometer-scale resolution. DESIGN: Survey optical coherence tomographic examination of the retina, including the macula and optic nerve head in normal human subjects. SETTING: Research laboratory. PARTICIPANTS: Convenience sample of normal human subjects. MAIN OUTCOME MEASURES: Correlation of optical coherence retinal tomographs with known normal retinal anatomy. RESULTS: Optical coherence tomographs can discriminate the cross-sectional morphologic features of the fovea and optic disc, the layered structure of the retina, and normal anatomic variations in retinal and retinal nerve fiber layer thicknesses with 10-microns depth resolution. CONCLUSION: Optical coherence tomography is a potentially useful technique for high depth resolution, cross sectional examination of the fundus. PMID- 7887847 TI - Age-related eye disease and survival. The Beaver Dam Eye Study. AB - OBJECTIVE: To investigate the relationship of cataract, age-related maculopathy, glaucoma, and visual impairment to survival in the population-based Beaver Dam Eye Study. DESIGN: In this population-based study, visual acuity was measured with use of standardized protocols. At baseline, stereoscopic color fundus photographs and color slit-lamp and retroillumination photographs were graded in a masked fashion to determine the presence of age-related maculopathy and cataract, respectively. Deaths were ascertained by contacting family members, daily review of obituaries, and use of vital status records. PARTICIPANTS: Subjects aged 43 through 84 years who lived in Beaver Dam, Wis, were identified and examined between 1988 and 1990. RESULTS: From the time of the baseline examination until a median of 4 years later, 9.5% (467/4926) of the population had died. After correcting for age and sex, poorer survival was associated with more severe nuclear sclerosis (5-year survival of 88.9% for the most severe compared with 94.1% for the least severe stage) and visual impairment (5-year survival of 87.5% for impaired compared with 91.8% for unimpaired vision). However, after controlling for systemic factors, only more severe nuclear sclerosis in people without diabetes was significantly associated with poorer survival (hazard ratio per level of severity, 1.19; 95% confidence interval, 1.00 to 1.40). CONCLUSIONS: These data suggest that after controlling for age and sex, nuclear sclerotic cataract severity, cataract surgery, and visual impairment are risk indicators for poorer survival. Cortical cataract, posterior subcapsular cataract, glaucoma, and age-related maculopathy were unrelated to poorer survival. PMID- 7887848 TI - Metastasis of adenocarcinoma of the lung to optic nerve sheath meningioma. AB - A 71-year-old woman developed chronic progressive visual loss in the right eye and computed tomographic scan showed enlargement of the intraorbital optic nerve consistent with optic nerve sheath meningioma. Over 12 years, the contralateral optic nerve was not clinically affected, and serial neuroradiologic imaging showed no evidence of intracranial tumor extension. Death occurred from metastatic adenocarcinoma of the lung 14 years after initial visual loss. Examination of the postmortem specimen of optic nerve and chiasm revealed extradural extension of meningioma with spread to the region of the optic chiasm and hypothalamus. A large focus of metastatic adenocarcinoma was present within the intraorbital portion of the meningioma. Carcinoma metastatic to intracranial meningioma is rare; to our knowledge, this is the first reported case in an optic nerve sheath meningioma. Neuroimaging may be inadequate to predict the value of tumor excision in preventing intracranial spread of optic nerve sheath meningioma. PMID- 7887849 TI - Diabeteslike proliferative retinal changes in galactose-fed dogs. AB - OBJECTIVE: To determine whether diabeteslike lesions associated with the proliferative stage of diabetic retinopathy develop in galactose-fed dogs, since studies designed to define the complex biochemical effects of prolonged hyperglycemia on retinal vessels have been hampered by the lack of an animal model that mirrors both the early and advanced stages of diabetic retinopathy. METHODS: Eyes from 9-month-old male beagles fed a daily diet containing either 30% nonnutrient filler (control diet) or 30% galactose (galactose diet) for up to 84 months were enucleated and histologically examined. RESULTS: Retinal vessel changes associated with the proliferative stage were observed in two of nine galactose-fed dogs while the remainder demonstrated retinal changes that included the appearance of microaneurysms, acellular capillary beds associated with areas of nonperfusion, and intraretinal microvascular abnormalities. Proliferative changes were evidenced by the formation of preretinal fibrous membranes and the appearance of fibrovascular membranes on the retinal surface and on the posterior hyaloid membrane. No retinal lesions were observed in similar dogs fed a control diet for up to 84 months. CONCLUSION: The galactose-fed dog appears to be the first animal model that can develop diabeteslike retinal vessel changes associated with both the early and advanced stages of retinopathy, including the proliferative stage. PMID- 7887850 TI - Retinopathy in galactosemic dogs continues to progress after cessation of galactosemia. AB - BACKGROUND: Progression of diabetic retinopathy in human subjects and animal models is difficult to halt promptly by intensified insulin therapy and strict glycemic control. OBJECTIVE: To learn whether this resistance to arrest is peculiar to diabetes and insulin therapy or is a characteristic of hyperglycemia itself, we have determined the effect of intervention on diabetic-like retinopathy in a non-diabetic animal model, the galactose-fed dog. METHODS: Dogs were given a 30% galactose diet. At the end of 24 months, the dogs were divided into two groups, one of which continued to receive the galactose diet, while the second immediately began receiving the diet minus galactose. All animals were killed after 60 months of study. RESULTS: Consumption of the galactose-rich diet resulted, as expected, in galactosemia evident by elevated hemoglobin A1, plasma nonenzymatically glycated protein, and erythrocyte polyol concentrations, each of which decreased to normal levels following withdrawal of dietary galactose. Retinopathy was found to be equivocal at the end of 24 months of the galactose diet and subsequently progressed significantly despite cessation of the galactose diet. CONCLUSION: The fact that retinopathy did not halt promptly at intervention is consistent with previous data from diabetic dogs and suggests that the vascular lesions may be due to sequelae of excessive tissue aldohexose that are not promptly corrected by correction of the aldohexose level. PMID- 7887851 TI - Epiretinal membrane formation. Light and electron microscopic study in an experimental rabbit model. AB - OBJECTIVE: To clarify the role of retinal glial cells in epiretinal membrane formation. METHODS: We injected autologous whole blood into the vitreous cavity of albino rabbits and studied the events in the vitreoretinal interface at intervals during the course of 1 year by light and electron microscopy. RESULTS: Epiretinal membranes were first found 2 weeks after the treatment. At this stage, epiretinal membranes were composed of both glial cells and macrophages. Mitotic figures of glial cells were found in the retina. The nuclei of glial cells migrated, passing through the inner limiting membrane and onto the retinal surface. At 6 months, macrophages and red blood cells disappeared from the epiretinal membranes. The epiretinal membranes became thicker with time. Finally, these epiretinal membranes were composed solely of glial cells. CONCLUSIONS: At the early stage, macrophages participate with glial cells in epiretinal membrane formation; however, glial cells are the main constituent of epiretinal membranes during the late stage. PMID- 7887852 TI - Effects of preservative-free artificial tear solutions on corneal epithelial structure and function. AB - OBJECTIVES: To test the efficacy of a bicarbonate-containing artificial physiologic tear solution (solution PT) in providing an environment in which the damaged corneal epithelium can recover its normal barrier function and to compare this solution with other available artificial tears. Also, to investigate the effects on the corneal mucin layer and epithelial ultrastructure. METHODS: The corneal epithelial permeability of anesthetized rabbits was increased by exposure to 0.1% benzalkonium chloride. The corneas were then exposed to solution PT, with or without bicarbonate, or one of four commercially available artificial tear solutions for 1.5 hours, followed by a 5-minute exposure to 5(6) carboxyfluorescein. Frozen sections of the corneas were examined by fluorescence microscopy. The fluorescence intensity (FI) of the epithelium was measured by image analysis. Undamaged corneas exposed to tear solutions were examined by transmission electron microscopy after fixation of the mucin layer with cetylpyridinium chloride. RESULTS: The FI of corneas damaged by benzalkonium chloride was increased threefold above those of undamaged controls. Damaged corneas treated with either of two commercial isotonic tear solutions partially recovered their barrier function, but the FI did not reach control levels. Corneas treated with hypotonic solutions containing ethylenediaminetetraacetic acid (EDTA) did not recover. In contrast, the FI of corneas treated with solution PT returned to control levels. This effect was lost in the absence of bicarbonate. Solution PT and the two isotonic solutions maintained normal corneal ultrastructure and mucin layer. Lack of bicarbonate in solution PT resulted in focal damage to superficial epithelial cells, whereas the EDTA-containing solutions destroyed the first two cell layers and reduced the mucin thickness. CONCLUSIONS: Bicarbonate-containing solution PT is superior to the other tear solutions tested in promoting recovery of the damaged corneal epithelial barrier and maintaining normal ultrastructure. The presence of bicarbonate appears to be essential to this process. PMID- 7887853 TI - Trabecular meshwork hemorrhage in a patient with sickle cell trait. PMID- 7887854 TI - A large oncocytoma of the caruncle. PMID- 7887855 TI - Epidemiology of arterial surgery. PMID- 7887856 TI - Carotid endarterectomy: options and outcomes. PMID- 7887857 TI - Carotid endarterectomy for asymptomatic carotid artery stenosis: patients with severe bilateral disease a high risk subgroup. AB - Carotid endarterectomy if advised for asymptomatic disease must be associated with a low peri-operative morbidity and mortality and satisfactory long-term results. Over a 12 year period between 1978-1989 181 carotid endarterectomies were performed on 163 patients with asymptomatic carotid artery stenosis. There were 112 males and 51 females with a mean age of 64.9 years. All patients had a high-grade lesion (> 70% stenosis). The combined operative mortality and stroke rate was 2.8%. On long-term follow up six patients suffered a stroke. Only one patient however sustained a stroke in the same territory as the previously operated carotid artery. Four years following surgery 78% of patients were alive. Carotid restenosis or occlusion occurred in 8.3% of the remaining patients, all of whom were asymptomatic. All the immediate postoperative strokes occurred in patients with severe bilateral carotid artery disease. These patients with severe bilateral disease appear to constitute a high risk sub-group for peri-operative stroke. The role of 'normal pressure-hyperperfusion breakthrough' syndrome as the presumed aetiology of two of the postoperative cerebral haemorrhages is discussed. PMID- 7887858 TI - Trends in the practice of arterial surgery in Western Australia. AB - An overview of arterial surgery in Western Australia and the Department of Vascular Surgery at Royal Perth Hospital was undertaken for the ten year period from 1983 to 1992. The annual number of arterial procedures increased 116% from 937 to 2027 and lower limb amputations increased 44% from 335 to 483. Five arterial procedures were examined in detail. There was a marked increase in carotid endarterectomy and angioplasty, a moderate increase in aortic aneurysm repair and a small increase in aortofemoral and femoropopliteal bypass surgery. The major amputation rate was not influenced by bypass surgery. It rose from 113 per million population in 1983 to a peak of 148 in 1986, and then fell to 113 per million population in 1992. From June 1982 to June 1992 the population of Western Australia rose 24%, from 1.34 to 1.66 million (and for persons 60 years and over, rose 38% from 0.16 to 0.23 million). At Royal Perth Hospital similar trends were observed. Mean duration of operation for all vascular procedures and for the individual procedures of carotid endarterectomy, angioplasty, aortic aneurysm repair and aortofemoral and femoropopliteal bypass remained unchanged. Average length of stay decreased for carotid endarterectomy (29%) and angioplasty (74%), but remained unchanged for aortic aneurysm repair and aortofemoral and femoropopliteal bypass. PMID- 7887859 TI - Predicting healing of lower limb ulcers. AB - Management of ischaemic ulcers in patients with compromised peripheral arterial circulations relies on the physical examination and the simple, non-invasive assessment of arterial supply. This study aims to determine if transcutaneous oxygen pressure (tcPO2) measurement can improve management decisions based on ankle or toe systolic blood pressure measurement. Twenty-two consecutive patients with ischaemic ulcers had tcPO2 measured and the ankle/brachial (ABI) and toe/brachial (TBI) indices calculated. Two months after surgery 12 of 22 (55%) ulcers were healing and 10 (45%) were indolent. Postoperative tcPO2 values were predictive of wound outcome (P < 0.001). A tcPO2 > 31 mmHg was invariably associated with healing whilst a tcPO2 < 28 mmHg was associated with indolence. Ankle/brachial indices and TBI were unable to be calculated in all patients due to falsely elevated pressures and hallux amputations, respectively, and neither was predictive of outcome (ABI P = 0.152, TBI P = 0.069). The response to revascularization was less in diabetic patients with a mean tcPO2 increase of 18 mmHg compared to non-diabetic patients with a mean tcPO2 increase of 37 mmHg. TcPO2 measurement appears to be a reliable technique that can influence ischaemic ulcer management. PMID- 7887860 TI - Current status of coronary artery bypass grafting in patients 70 years of age and older. AB - One hundred and seventy patients 70 years of age and older underwent isolated coronary artery bypass grafting (CABG) from January 1990 to December 1991 at St. Vincent's Hospital, Melbourne, Australia. The clinical records of these patients were analysed to investigate whether elderly patients could undergo safe coronary artery surgery and to determine the factors affecting the outcome. The 30 day or in-hospital mortality was 2.9% (5/170), with 80% (4/5) of the deaths due to cardiac causes. Major postoperative complications occurred in 22.3% (38/170) patients. The median postoperative hospital stay for the patients was 8 days (range 3-103 days). Univariate analysis identified hypertension and female gender as pre-operative risk factors and intraaortic balloon pump, prolonged ventilation, infarct, tamponade, need for inotropes, renal failure and a high APACHE II scores in the intensive care unit as postoperative significant risk factors for operative mortality. There was a trend towards increased mortality with emergency operations; the operative mortality was 2.1% (2/97) for elective operations, 3.1% (2/64) in urgent cases and 11.1% (1/9) for emergencies. Multivariate logistic regression analysis identified prolonged mechanical ventilation, perioperative infarct and APACHE II score as significant independent predictors of mortality. The low operative mortality indicates that elderly patients can undergo safe revascularization. A high incidence of complications necessitates careful monitoring but age per se should not be considered a contraindication to isolated CABG. PMID- 7887861 TI - Complications of bush thoracotomy in the Highlands of Papua New Guinea. AB - Bush thoracotomy is still practised in the South Western Highlands of Papua New Guinea, by traditional bush doctors. These bush thoracotomies are performed with the aim of letting out the 'bad blood' that is believed to have collected in the body cavities following injuries. During a 3 year period between 1989 and 1992, 183 patients with complications of bush thoracotomy were treated at the Sopas Hospital in the Highlands of Papua New Guinea. Of these patients, 55 had chest wall infections only, without any pleural involvement. Of the patients with empyemas, 14 were treated by decortication of the empyema with one death and all remaining patients were treated by drainage procedures with one death. We recommend early treatment by adequate drainage of the empyema and, where feasible, early decortication. Continuing education to eradicate the procedure, and provision of adequate surgical facilities for management of complications, should be the long-term aim for this continuing problem. PMID- 7887862 TI - Post-cholecystectomy haemobilia: enjoying a renaissance in the laparoscopic era? AB - Trauma to the right hepatic artery during biliary surgery can lead to false aneurysm formation. Subsequent rupture into the biliary system, which may occur after a considerable delay, will then result in major haemobilia. This report details five cases referred to the Royal Melbourne Hospital over a 12 month period, four of which followed initial laparoscopic procedures, and emphasizes important management procedures to prevent and treat this previously rare complication. PMID- 7887863 TI - Laparoscopic exploration of intra- and extrahepatic bile ducts and T-tube drainage. AB - Laparoscopic cholecystectomy (LC) has rapidly become the procedure of choice for the management of patients with gall-bladder stones. This contrasts with patients who have common bile duct and intrahepatic duct stones who still usually need an open operation. On the basis of experience of a number of LC by one surgeon and animal experiments, we have completed laparoscopic exploration of both intra- and extrahepatic ducts and T-tube drainage of 57 patients with intra- and extrahepatic bile duct calculi over 13 months during 1992-1993 with satisfactory results. The average operating time was 150 min, with a range of 100 to 220 min. Most patients were mobile and on oral fluids within 24 h postoperative. Average hospital stay was 4 days. Retained stones were found via T-tube cholangiography in four patients (7%) and for each patient these were removed by fibre-optic choledochoscope 2 weeks postoperatively. Laparoscopic exploration of intra- and extrahepatic bile ducts is achievable by experienced surgeons and may be particularly helpful for patients who are not a good operative risk. PMID- 7887864 TI - Technique and complications of percutaneous endoscopic gastrostomy in children. AB - Percutaneous endoscopic gastrostomy (PEG) is now a well-established technique in children. In this study of 63 children (mean age 7.8 years, youngest 2.4 months), technical problems associated with insertion of the gastrostomy tube, and complications related to the procedure, were analysed. Complications included wound infection, oesophageal injury (probably sustained during extraction of the guide wire) and symptomatic gastro-oesophageal reflux (GOR) occurring after PEG insertion. Many of these complications can be avoided or reduced in likelihood by refinements to the technique of insertion. PMID- 7887865 TI - Retroperitoneal schwannoma: a case series and review. AB - Schwannomas account for only a small percentage of retroperitoneal tumours. Presentation is typically varied and non-specific and pre-operative diagnosis is difficult. Herein are described five cases of retroperitoneal schwannoma. Presentation was varied, ranging from abdominal pain, abdominal mass, obstructed labour or an incidental finding. All patients had either an abdominal computed tomography scan and/or ultrasound performed. Pre-operative biopsy either by fine needle aspiration (in one patient) or core biopsy in two patients was unhelpful. In four patients with smaller tumours, complete excision was possible with no apparent long-term morbidity and no clinical evidence of recurrent tumour with follow up from 3.5 months to 11 years. For the largest tumour, complete surgical excision was not attempted as it would have entailed significant morbidity. PMID- 7887866 TI - The effect of infrarenal aortic cross clamping and declamping on renal function in the pig. AB - Renal insufficiency following periods of infrarenal aortic cross clamping has been reported by some investigators but not by others, and conflicting views have been expressed concerning the ability of renal autoregulation to overcome the adverse circulatory effects of cross clamping. The object of this study was to examine the blood flow distribution to four layers within the renal cortex (subcapsular to juxtamedullary) and measure global renal function following application and release of an aortic cross clamp after 90 min. Nine juvenile female pigs weighing 25 to 50 kg were anaesthetized and subjected to intensive physiological monitoring. Throughout the study the blood pressure and cardiac output were maintained as close as possible to control levels by fluid administration and varying the depth of anaesthesia. Renal cortical blood flow was estimated by means of radionuclide labelled microspheres and global renal function was determined by the measurement of creatinine clearance. The aortic cross clamp was applied for 90 min immediately distal to the renal arteries and proximal to the inferior mesenteric artery. Cardiovascular and renal parameters were recorded on four occasions during each experiment, prior to, 10 and 60 min after cross clamping, and 30 min after clamp release. No significant changes in cardiac output, systemic blood pressure of global renal function were recorded during the study. There was, however, a significant fall in renal blood flow following release of the aortic cross clamp but this was not associated with any significant redistribution of blood flow within the renal cortex. In the pigs studied, the application of an infrarenal aortic cross clamp did not have any adverse effects on the cardiovascular system or on global renal function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7887867 TI - Vascular surgery. AB - Recent developments in vascular surgery have occurred in many areas. The topics of intimal hyperplasia and reperfusion injury are the subject of much current research and possible methods of treatment are at an early stage of development. Advances in perioperative care have contributed to a reduction in mortality and morbidity. Endovascular techniques are being employed widely but the indications for their use are not yet agreed. The laboratory assessment of patients has been enhanced by the availability of duplex ultrasound scanning. The indications for carotid endarterectomy are becoming less controversial and a more aggressive approach is being taken in patients with abdominal aortic aneurysm. In patients with chronic lower limb ischaemia, long bypass grafts to the level of the ankle are being performed more frequently. The use of temporary shunts in patients with major arterial injuries appears to improve the results of treatment. PMID- 7887868 TI - Verrucous carcinoma of the temporal bone. AB - A case report of a patient suffering from severe otalgia for 12 months and intermittent otorrhoea over a 53 year period is presented. Diagnosed as verrucous carcinoma of the temporal bone, this is only the ninth case found in the literature. The difficulty of histological diagnosis and subsequent management are important features. PMID- 7887869 TI - Bilateral renal oncocytoma: case report and implications in renal tumour management. AB - Renal oncocytomas are uncommon benign tumours that have recently been recognized as a unique pathological entity. These lesions may attain considerable size; however, most present as an asymptomatic incidental finding. Although usually solitary, these tumours are occasionally multicentric or bilateral at presentation. Retrospective studies suggest that oncocytoma may account for up to 5% of tumours previously classified as well-differentiated renal cell carcinoma. At present, conservative management is hampered by difficulty in establishing a confident pre-operative or intra-operative diagnosis. A case of bilateral asymptomatic renal oncocytoma is presented, and the implications of this lesion for the management of renal tumours is discussed. PMID- 7887870 TI - Acute cholecystitis in a double gall-bladder. PMID- 7887871 TI - Clinical versus nonclinical panic: a test of suffocation false alarm theory. AB - Klein's suffocation false alarm theory of panic implies that suffocation sensations should distinguish clinical from nonclinical panic attacks better than should other symptoms. To test this theory, we conducted phenomenologic comparisons between attack patterns of patients with panic disorder and community subjects who had experienced unexpected panic. Effect size and multivariate analyses revealed that three cognitive symptoms best discriminated clinical from nonclinical panic (fears of dying, heart attack, and loss of control). These findings are consistent with cognitive theories of panic. Although lacking the discriminative power of cognitive symptoms, suffocation sensations had the largest effect size of any physiological symptom. Accordingly, suffocation sensations may be especially likely to give rise to the catastrophic thoughts that best discriminate clinical from nonclinical panic. PMID- 7887872 TI - The utilization of nonpatient samples in the study of obsessive compulsive disorder. AB - Obsessive compulsive disorder (OCD) is increasingly studied in nonpatients, primarily through the selection of individuals who score high on a self-report measure of OCD. The usefulness of this methodology for understanding OCD presupposes that some of the individuals in the high-scoring group meet diagnostic criteria for OCD, that the obsessive-compulsive behaviors in the high scoring individuals are stable across time to a certain degree, and that the features associated with OCD in patients also are found in the high-scoring nonpatients. Two studies are reported which provide support for these three assumptions. Together the studies suggest that OCD can be productively examined by the selection of individuals who score high on a self-report measure of OCD. Cautions in the use of this methodology for the study of OCD are also noted. PMID- 7887873 TI - Applied relaxation vs cognitive behavior therapy in the treatment of panic disorder. AB - The present study investigated the efficacy of a coping-technique, applied relaxation (AR) and cognitive behavior therapy (CBT), in the treatment of panic disorder. Thirty-eight outpatients fulfilling the DSM-III-R criteria for panic disorder with no (n = 30) or mild (n = 8) avoidance were assessed with independent assessor ratings, self-report scales and self-observation of panic attacks before and after treatment, and at a 1-yr follow-up. The patients were treated individually for 12 weekly sessions. The results showed that both treatments yielded very large improvements, which were maintained, or furthered at follow-up. There was no difference between AR and CBT on any measure. The proportion of panic-free patients were 65 and 74% at post-treatment, and 82 and 89% at follow-up, for AR and CBT, respectively. There were no relapses at follow up, on the contrary 55% of the patients who still had panic attacks at post treatment were panic-free at follow-up. Besides affecting panic attacks the treatments also yielded marked and lasting changes on generalized anxiety, depression and cognitive misinterpretations. The conclusion that can be drawn is that both AR and CBT are effective treatments for panic disorder without avoidance. PMID- 7887874 TI - Inflated responsibility in obsessive compulsive disorder: validation of an operational definition. AB - An excessive sense of responsibility has been identified in obsessive-compulsive disorder (OCD) where patients evaluate their thoughts in terms of the harm they could cause to themselves or others. In a new definition, responsibility was defined as the belief that one possesses pivotal power to provoke or prevent subjective crucial negative outcomes. In order to empirically test the validity of this definition, two studies used a semi-idiographic design to evaluate responsibility across ambiguous situations related to major OCD themes like contamination, verification, somatic concerns, loss of control, making errors, sexuality and magical thinking. In the first study, 397 volunteer adults participated in the experiment. For each situation, subjects briefly described a possible negative outcome and then rated this outcome on four dimensions: (1) probability; (2) severity; (3) influence; and (4) pivotal influence, using a 9 point Likert scale. Finally Ss rated perceived responsibility and personal relevance. Highly relevant situations were retained for the final analysis. Regression analysis suggested that influence and pivotal influence were better predictors of responsibility ratings than probability and severity. The second study examined the effect of the order of the questions on the responsibility ratings. A first group of Ss (n = 85) answered the Responsibility Questionnaire (RQ) in the original order, while a second group (n = 53) rated responsibility before the other ratings. Regression analysis showed that although proportion of variance explained diminished when the order was reversed, pivotal influence was still the best predictor of responsibility. Results are discussed in terms of current models of OCD and implications for future research and cognitive treatment are identified. PMID- 7887875 TI - The looming of spiders: the fearful perceptual distortion of movement and menace. AB - The current study examined the relation between the perception that fear-stimuli are looming and fearful cognitive distortions. As hypothesized, high-fear-of spider Ss were significantly more likely than low-fear Ss to imagine that a spider in a room would move rapidly and selectively to them in proximity, rather than towards three other individuals in the same physical space. This finding was observed with a measure of perceptual-cognitive distortion as well as with self reports. High-fear Ss were also more likely to perceive spiders as angry and belligerent, as intending to move towards them, and as singling them out from other people. These results suggest that perceptions of looming danger and fearful cognitive distortions are closely linked phenomena. Finally, the perception that spiders are looming and the other cognitive variables could be used to successfully classify the fear-group memberships of the Ss in 98% of the cases. Perceptions that spiders are looming made the single largest unique contribution to the discriminant classification function. PMID- 7887876 TI - Nonclinical hair-pulling: affective correlates and comparison with clinical samples. AB - The purposes of the current study were to examine the affective states associated with hair-pulling in a nonclinical sample and to compare levels of general psychopathology in nonclinical hair-pullers and clinic patients with trichotillomania (TM) or obsessive-compulsive disorder (OCD). Subjects included 66 college undergraduates who engaged in hair-pulling unrelated to grooming, 18 patients with TM and 29 patients with OCD. Dimensional (but not categorical) ratings of affective experiences in the nonclinical sample indicated that hair pulling was associated with decreases in tension, boredom, anger and sadness. Further, the relationship between emotional experiences before and after hair pulling was more salient than the pre-during relationship conceptualized as central in current diagnostic criteria for TM. Comparisons of psychopathology in nonclinical and clinical samples failed to support a continuum notion of increasing symptomatology in nonclinical pullers, TM patients and individuals with OCD. Some evidence of increased pathology in nonclinical pullers relative to TM patients was obtained, as was further support for a distinction between TM and OCD. Implications of this investigation for conceptualization of TM are discussed. PMID- 7887877 TI - Emotional processing in survivors of the Jupiter cruise ship disaster. AB - Twenty-three survivors of the Jupiter cruise ship disaster completed the Impact of Events Scale, a measure of intrusion and avoidance, as well as measures of arousal and affect at two points in time: between 3 and 7 months (Time 1) and between 12 and 14 months (Time 2) following the event. The aim of the present study was to explore the relationship between intrusion and avoidance and symptoms of depression and anxiety. The results suggest that although higher scores on intrusion and avoidance are strongly associated with poorer psychological outcome at each point in time, it is only intrusion which may be predictive of later symptoms. Avoidance would seem to be a response to early distress. These data are discussed with reference to a cognitive--emotional processing model of post-traumatic stress disorder. PMID- 7887878 TI - Social anxiety, fear of negative evaluation and the detection of negative emotion in others. AB - The present study sought to investigate whether social anxiety is associated with enhanced ability to detect negative emotion in others. Subjects scoring high and low on Fear of Negative Evaluation (FNE) performed two tasks before and after a social threat induction. The first task involved identifying the affect (negative vs neutral) in briefly presented (60 msec) slides of faces. The second involved rating the overall emotion conveyed in brief video clips of an actor and detecting discrepancies in the affect conveyed by the visual and auditory channels of the video. Overall the results suggest that high social anxiety subjects have a bias towards identifying others' emotional expressions as negative in the absence of an enhanced ability to discriminate between different emotional states in others. Implications and limitations of the results are discussed. PMID- 7887879 TI - Treatment of claustrophobias and snake/spider phobias: fear of arousal and fear of context. AB - Forty-nine individuals with fears of snakes or spiders, and 21 individuals with claustrophobic fear were assigned randomly to two sessions of either in vivo exposure plus relaxation or in vivo exposure plus disconfirmation of misappraisals of bodily sensations. Behavioral, subjective and physiological assessments were conducted pre and post treatment, and 4 weeks later. As hypothesized, disconfirmation of misappraisals of bodily sensations benefited claustrophobic fear reduction, but had little effect on fears of snakes or spiders. However, differential treatment effects failed to generalize to nontargetted phobic situations, or generalize over time. In addition, the two treatments affected basic beliefs about arousal sensations equally. PMID- 7887880 TI - Acquisition and maintenance of dental anxiety: the role of conditioning experiences and cognitive factors. AB - This study presents a contribution to the understanding of the mechanisms that are involved in the development and maintenance of dental anxiety. Subjects were 224 undergraduate psychology students who completed questionnaires regarding dental anxiety, painful and traumatic experiences, negative cognitions, dental beliefs, and how their attitude to dental treatment had changed during their life. The results showed that both the extent to which earlier dental treatments were perceived as painful and the extent to which these incidents were reported as traumatic were significantly related to dental anxiety. Evidence was also found to support the latent inhibition hypothesis, which predicts that patients less easily acquire dental anxiety in case they received a number of relatively painless treatments prior to conditioning. Both findings confirmed those earlier obtained by Davey in a conceptually similar design (Behaviour Research and Therapy, 27, 51-58, 1989). In addition, frequency of negative cognitions about dental treatment and dental anxiety appeared to be positively related (r = 0.74; P < 0.001). Significant differences were found between highly anxious Ss and Ss showing low levels of anxiety on a variety of expectations and beliefs related to undergoing dental treatment. The results are discussed in terms of a cognitive behavioural perspective of dental anxiety. PMID- 7887881 TI - Covariation bias and the return of fear. AB - Several studies have indicated that phobic fear is accompanied by a covariation bias, i.e. that phobic Ss tend to overassociate fear relevant stimuli and aversive outcomes. Such a covariation bias seems to be a fairly direct and powerful way to confirm danger expectations and enhance fear. Therefore, it has been suggested that covariation bias is an important factor in the maintenance of phobic fear. However, thus far there are no empirical data available to exclude the alternative possibility that covariation bias is a mere epiphenomenon of fear. To explore the "causal" status of covariation bias, successfully treated spider phobics who participated in an earlier study on covariation bias were asked to complete a Spider Phobia Questionnaire at 2 yr follow up. Results indicate that Ss who displayed a covariation bias immediately after treatment are more vulnerable to relapse than Ss who did not show such a bias. This finding strengthens the idea that covariation bias may enhance fear, thereby contradicting the suggestion that covariation bias is a mere epiphenomenon of phobic fear. PMID- 7887882 TI - Danger expectancies and insight in acrophobia. AB - Differences between phobic and normal subject perceptions of danger were examined. Fifty-nine height phobic patients and a matched set of normal controls gave danger ratings before and during a height avoidance test on a triple extension ladder. Before the test acrophobic patients: (1) gave higher estimates of the probability of falling from the ladder than normals did; (2) gave higher estimates of the injuries that would result from falling, and; (3) believed their excessive levels of anticipated anxiety were more reasonable and appropriate to the demands of the situation than did normals. In addition, during the height avoidance test the differences between the two groups grew as phobic danger estimates increased while control group estimates did not. Finally, moderate, but inconsistent, relationships were obtained between phobic danger ratings and anxiety and avoidance. The implications of these findings for expectancy models of anxiety are discussed. The results challenge the view that phobic patients have complete insight into the inappropriateness of their own distress. PMID- 7887883 TI - Psychometric characteristics and validity of the Dutch adaptation of the Buss Durkee Hostility Inventory (the BDHI-D). AB - Data are presented on the factorial structure, internal consistency, and validity of the Dutch adaptation of the Buss-Durkee Hostility Inventory (the BDHI-D). Factor analyses of the responses of 463 subjects revealed two scales measuring Overt Aggression and Covert Aggression. The reliability of both subscales is good. Concordance with other self-report measures reveals satisfactory convergent and divergent validity. PMID- 7887884 TI - Validation of the Dutch adaptation of the Buss-Durkee Hostility Inventory. AB - The validity of the Dutch adaptation of the Buss-Durkee Hostility Inventory was investigated. On the basis of the ratings of the staff of a residential treatment center for adolescents with conduct disorders, two contrast groups (high versus low aggression) were formed. In all, 67 male adolescents participated in the study. The subscales of the inventory clearly discriminated between the two groups. A discriminant function analysis revealed that the inventory could correctly classify the subjects into aggressive and non-aggressive with 96% accuracy. The pattern of correlations between the inventory and an anger scale and a social desirability scale provide further support for the construct validity of the instrument. PMID- 7887886 TI - Cloning and expression of protein tyrosine phosphatase-like protein derived from a rat pheochromocytoma cell line. AB - A novel protein [designated protein tyrosine phosphatase-like protein (PTPLP)] which is distantly related to receptor-type protein tyrosine phosphatases (PTPases) was cloned from a rat pheochromocytoma cell line. The PTPLP was detected exclusively in the brain. Overexpression of the PTPLP decreased the basal PTPase activity of COS-7 cells for Raytide. These results suggest that PTPLP may function as a negative regulator of PTPases in neuronal tissues. PMID- 7887885 TI - Protein damage and methylation-mediated repair in the erythrocyte. PMID- 7887887 TI - The cardiac myosin heavy chain Arg-403-->Gln mutation that causes hypertrophic cardiomyopathy does not affect the actin- or ATP-binding capacities of two size limited recombinant myosin heavy chain fragments. AB - Our aim was to investigate the potential functional consequences of myosin heavy chain (MHC) mutations identified in patients with familial hypertrophic cardiomyopathy. We observed the presence of a mutated beta-MHC mRNA in a formalin fixed paraffin-embedded myocardial tissue of a proband from family A, which Geisterfer-Lowrance et al. [Geisterfer-Lowrance, Kass, Tanigawa, Vosberg, McKenna, Seidman and Seidman (1990) Cell 62, 999-1006] identified as carrying the Arg-403 to Gln mutation. Recombinant DNA methods were then used to obtain size limited, soluble and undenatured fragments of mutated myosin subfragment 1 focused around the 403 mutation. The present analysis indicated that the 403 mutation did not quantitatively alter the actin- or ATP-binding capacities of two 246-residue or 524-residue-long recombinant MHC fragments containing this mutation. The absence of any apparent impact of the 403 mutation in the recombinant MHC fragments on interactions between actin and ATP is discussed in relation to numerous biochemical and structural reports which demonstrate the crucial role of the central MHC segment, where the 403 mutation occurs, in myosin functions. PMID- 7887888 TI - Both nuclear and mitochondrial cytochrome c oxidase mRNA levels increase dramatically during mouse postnatal development. AB - The steady-state levels of 13 of 16 cytochrome c oxidase (COX) mRNAs and mitochondrial DNA were measured during the postnatal development of mouse skeletal muscle, ventricle, kidney and brain as well as during the differentiation of mouse myoblasts into myofibres in cell culture. These experiments indicate that large co-ordinated increases in COX mRNA levels and isoform switching are important for the elaboration of this enzyme during postnatal development and demonstrate the importance of gene-regulatory mechanisms in controlling COX activity. On a per nucleus basis, the levels of the mitochondrial- and most nuclear-encoded COX mRNAs co-ordinately increase 3-10 fold during postnatal development, with the highest levels obtained in ventricle and skeletal muscle. However, concentrations of mitochondrial and nuclear COX mRNAs remain constant during the differentiation of myoblasts into fibres in cell culture. A gradual change from the liver to the heart isoform of COX subunit VIa mRNA occurs during postnatal development of skeletal muscle and ventricle and is nearly complete 3 days after the formation of myofibres in cell culture. Mitochondrial DNA increases proportionally with COX mRNAs during mouse postnatal development but not during myoblast differentiation in cell culture, in which mitochondrial DNA levels increase 5-fold and mitochondrial mRNA levels remain constant. This suggests that mitochondrial DNA replication may control mitochondrial RNA concentrations during postnatal development but not during myoblast differentiation in cell culture. PMID- 7887889 TI - Inhibition of complex I by hydrophobic analogues of N-methyl-4-phenylpyridinium (MPP+) and the use of an ion-selective electrode to measure their accumulation by mitochondria and electron-transport particles. AB - N-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of N-methyl-4 phenyl-1,2,3,6-tetrahydropyridine, kills dopaminergic neurons after its accumulation in mitochondria where it inhibits Complex I of the respiratory chain. MPP+ inhibits respiration by binding to both a hydrophobic and a hydrophilic site on Complex I and this inhibition is increased by the lipophilic tetraphenylboron anion (TPB-) which facilitates movement of MPP+ through membranes and its penetration to the hydrophobic binding site on Complex I. To investigate the inhibition of respiration by MPP(+)-like compounds, we have measured simultaneously NADH-linked mitochondrial respiration and the uptake and accumulation of the N-benzyl-4-styrylpyridinium and N-ethyl-4-styrylpyridinium cations in mitochondria using ion-selective electrodes. The data provide direct evidence that TPB- increases the inhibition not by increasing matrix concentration but by facilitating access to the inhibitory sites on Complex I. We have also compared the rates of uptake of MPP+ analogues of varied lipophilicity by the inner membrane and the development of inhibition of NADH oxidation, using an inverted mitochondrial inner membrane preparation and appropriate ion selective electrodes. These experiments demonstrated that the amount of MPP+ analogue bound to the inner membrane greatly exceeded the quantity required for complete inhibition of NADH oxidation. Moreover, binding to the membrane occurred much more rapidly than the development of inhibition with all MPP+ analogues tested. This suggests that the attainment of a correct orientation of these compounds within the membrane and the binding site may be a rate-limiting step in the development of inhibition. PMID- 7887890 TI - Allosteric modulation of oxygen binding to the three human embryonic haemoglobins. AB - Plasmid based yeast expression systems have been developed for the high-level expression of the three human embryonic haemoglobins Gower I (zeta 2 epsilon 2), Gower II (alpha 2 epsilon 2) and Portland (zeta 2 gamma 2). Physiochemical characterization of the three product haemoglobins show them to be in the 'native' state. Oxygen-binding studies show that, under what are usually considered physiological conditions, each of the embryonic haemoglobins shows a high oxygen affinity, coupled to a high degree of co-operativity. Allosteric modulation of the oxygen-binding properties of the three haemoglobins in response to organic phosphates and protons has been investigated. The various responses exhibited by the three haemoglobins are rationalized in terms of their amino acid sequences. PMID- 7887891 TI - Enzymic characterization of Bacillus subtilis GTP cyclohydrolase I. Evidence for a chemical dephosphorylation of dihydroneopterin triphosphate. AB - GTP cyclohydrolase I catalyses the first committing step in the biosynthesis of the pterin moiety of folic acid: conversion of GTP to dihydroneopterin triphosphate. GTP cyclohydrolase I of Bacillus subtilis was purified to homogeneity and shown to have a homo-octameric structure. The enzyme had an apparent Km for GTP of 4 microM and, in the absence of cations, a Vmax. of 80 nmol/min per mg of protein. K+ ions moderately increased its Vmax., whereas UTP and Ca2+ and Mg2+ ions drastically increased its Km for GTP. Dihydrofolate and other products of the folate and tetrahydrobiopterin pathways did not inhibit GTP cyclohydrolase I. In addition to their effect on the enzyme activity, Ca2+ and Mg2+ ions catalysed the chemical dephosphorylation of dihydroneopterin triphosphate to non-cyclic dihydroneopterin monophosphate, the substrate for the phosphomonoesterase reaction in folate biosynthesis. This dephosphorylation was specific and did not require the action of a phosphatase. We suggest a physiological role for Ca2+ ions and UTP in regulation of folate biosynthesis at the levels of GTP cyclohydrolase I and dephosphorylation of dihydroneopterin triphosphate. PMID- 7887892 TI - Developmental changes in carnitine palmitoyltransferases I and II gene expression in intestine and liver of suckling rats. AB - Carnitine palmitoyltransferase (CPT) I is expressed in the intestine of suckling rats; its mRNA increases very rapidly after birth, remains on a plateau until day 18 and decreases until weaning, when basal (adult) values are reached, which remain unchanged thereafter. CPT II mRNA values do not show any appreciable change in this period. CPT I and CPT II are expressed mainly in mucosa and, to a lesser extent, in the muscular part of the intestine. Intestinal expression of CPT I is maximal in duodenum and jejunum, whereas CPT II is expressed in a similar pattern throughout the whole intestine. Dam's milk may influence the intestinal expression of CPT I, since mRNA levels at birth are low but increase after the first lactation. Moreover, rats weaned at either day 18 or 21 decrease their mRNA levels. Apparently, CPT II gene expression is not influenced by the mother's milk. CPT I and CPT II are also expressed in the liver of suckling rats. Hepatic CPT I is maximal at day 3, and levels of CPT II mRNA do not change, in a similar fashion to that in intestine. The profile of expression of CPT I in liver and intestine strongly resembles that previously reported for mitochondrial 3 hydroxy-3-methyl-glutaryl-CoA synthase. PMID- 7887893 TI - Purification and characterization of the imidazoleglycerol-phosphate dehydratase of Saccharomyces cerevisiae from recombinant Escherichia coli. AB - The HIS3+ gene of Saccharomyces cerevisiae was overexpressed in Escherichia coli and the recombinant imidazoleglycerol-phosphate dehydratase (IGPD) purified to homogeneity. Laser-desorption and electrospray m.s. indicated a molecular ion within 2 units of that expected (23833.3) on the basis of the protein sequence, with about half of the polypeptide lacking the N-terminal formylmethionine residue. IGPD initially purified as an apoprotein was catalytically inactive and mainly a trimer of M(r) 70,000. Addition of Mn2+ (but not Mg2+) caused this to assemble to an active (40 units/mg) enzyme (Mn-IGPD) comprising of 24 subunits (M(r) 573,000) and containing 1.35 +/- 0.1 Mn atoms/polypeptide subunit. An enzyme with an identical activity and metal content was also obtained when the fermenter growth medium of recombinant Escherichia coli was supplemented with MnCl2, and IGPD was purified through as Mn-IGPD rather than as the apoenzyme and assembled in vitro. Inhibition by EDTA indicated that the intrinsic Mn2+ was essential for activity. The retention of activity over time after dilution to very low concentrations of enzyme (< 20 nM) indicated that the metal remained in tight association with the protein. A novel continuous assay method was developed to facilitate the kinetic characterization of Mn-IGPD. At pH 7.0, the Km for IGP was 0.10 +/- 0.02 mM and the Ki value for inhibition by 1,2,4-triazole, 0.12 +/- 0.02 mM. In contrast with other reports, thiols had no influence on catalytic activity. The activity of Mn-IGPD varied with enzyme concentration in such a way as to suggest that it dissociates to a less active form at very low concentrations. Significant inhibition by the product, imidazole acetol phosphate, was inferred from the shape of the progress curve. Titration with, the potent competitive inhibitor, 2-hydroxy-3-(1,2,4-triazol-1-yl)propyl phosphonate indicated that Mn-IGPD contained 0.9 +/- 0.1 catalytic sites/protomer. The activity nearly doubled in the presence of high concentrations of Mn2+; the apparent Ks for stimulation was 20 microM. The basis of this effect was obscure, since there was no corresponding increase in the titre of active sites. Neither was there a discernable shift in the values of Km or Ki (above), although exogenous Mn2+ did reduce the optimum pH for kcat, from 7.2 to 6.8. On the basis of a single site/subunit, the maximum rate of catalytic turnover at 30 degrees C was 32 s-1. PMID- 7887894 TI - Multiple native-like conformations trapped via self-association-induced hydrophobic collapse of the 33-residue beta-sheet domain from platelet factor 4. AB - Native platelet factor 4 (PF4) (70 residues) has a hydrophobic three-stranded anti-parallel beta-sheet domain on to which is folded an amphipathic C-terminal alpha-helix and an aperiodic N-terminal domain. The 33-amino acid beta-sheet domain from PF4 (residues 23-55) has been synthesized and studied by c.d. and n.m.r. At 10 degrees C and low concentration, peptide 23-55 appears to exist in aqueous solution in a random-coil distribution of highly flexible conformational states. Some preferred conformation, however, is observed, particularly within a relatively stable chain reversal from Leu-45 to Arg-49. As the peptide concentration and/or temperature is increased, a new conformational state(s) appears and intensifies as slowly exchanging (600 MHz 1H-n.m.r. chemical-shift time scale) random-coil resonances disappear. Hill plots of the concentration dependence indicated mostly tetramer formation as found in native PF4. Although apparent resonance linewidths in aggregate state(s) are of the order of 100 Hz, sequence-specific assignments for most resonances could be made. N.m.r./nuclear Overhauser effect structural analysis indicates the formation of multiple native like anti-parallel beta-sheet conformations, kinetically trapped via subunit association-induced hydrophobic collapse and stabilized by low-dielectric electrostatic interactions among/between Gly-28 and Lys-50 in opposing subunits. Results are discussed in terms of protein folding. PMID- 7887895 TI - Oxidative modulation and inactivation of rabbit cardiac adenylate deaminase. AB - Oxidative stress and adenine nucleotide catabolism occur concomitantly in several disease states, such as cardiac ischaemia-reperfusion, and may act as synergistic determinants of tissue injury. However, the mechanisms underlying this potential interaction remain ill-defined. We examined the influence of oxidative stress on the molecular, kinetic and regulatory properties of a ubiquitous AMP-catabolizing enzyme, adenylate deaminase (AMPD) (EC 3.5.4.6). To this intent, rabbit heart AMPD and an H2O2/ascorbate/iron oxidation system were employed. Enzyme exposure to the complete oxidation system acutely impaired its catalytic activity, lowered the Vmax. by 7-fold within 5 min, and rendered the enzyme unresponsive to nucleotide effectors. Irreversible AMPD inactivation resulted within about 15 min of oxidative insult and was not prevented by free-radical scavengers. Oxidative stress did not affect the molecular mass, tetrameric nature, Km, immunoreactivity or trypsinolytic pattern of the enzyme; nor did it induce carbonyl formation, Zn2+ release from the holoenzyme or net AMPD S-thiolation. This injury pattern is inconsistent with a radical-fragmentation mechanism as the basis for the oxidative AMPD inactivation observed. Rather, the sensitivity of the enzyme to both S-thiolation and thiol alkylation and the significant (3 of 9/mol of denatured enzyme) net loss of DTNB-reactive thiols on exposure to oxidant strongly implicate the conversion of essential thiol moieties into stable higher oxidation states in the oxidative inactivation of cardiac AMPD. The altered thiol status of the enzyme on oxidative insult may prohibit a catalytically permissible conformation and, in so doing, increase AMP availability to 5'-nucleotidase in vivo. PMID- 7887896 TI - Tissue- and cell-specific expression of Ins(1,4,5)P3 3-kinase isoenzymes. AB - The phosphorylation of Ins(1,4,5)P3 (InsP3) to Ins(1,3,4,5)P4 (InsP4) is catalysed by InsP3 3-kinase. Molecular-biological data have shown the presence of two human isoenzymes of InsP3 3-kinase, namely InsP3 3-kinases A and B. We have isolated from a rat thymus cDNA library a 2235 bp cDNA (clone B15) encoding rat InsP3 3-kinase B. Northern-blot analysis of mRNA isolated from rat tissues (thymus, testis, brain, spleen, liver, kidney, heart, lung and intestine) revealed that a rat InsP3 3-kinase B probe hybridized to a 6 kb mRNA in lung, thymus, testis, brain and heart. In contrast, Northern-blot analysis of the same tissues probed under stringent conditions with a rat InsP3 3-kinase A probe hybridized to a 2 kb mRNA only in brain and a 1.8-2.0 kb mRNA species in testis. Northern-blot analysis of three human cell lines (HL-60, SH-SY5Y and HTB-138) probed with a human InsP3 3-kinase B probe showed the presence of a 6 kb mRNA in all cell lines, except in the human neuroblastoma cell line (SH-SY5Y), where two mRNA species of 5.7 and 6 kb were detected. Using the same blot, no hybridization signal could be seen with a human InsP3 3-kinase A probe. Altogether, our data are consistent with the notion that the two InsP3 3-kinase isoenzymes, A and B, are specifically expressed in different tissues and cells. PMID- 7887897 TI - Human alpha-tocopherol transfer protein: cDNA cloning, expression and chromosomal localization. AB - alpha-Tocopherol transfer protein (alpha TTP), which specifically binds this vitamin and enhances its transfer between separate membranes, was previously isolated from rat liver cytosol. In the current study we demonstrated the presence of alpha TTP in human liver by isolating its cDNA from a human liver cDNA library. The cDNA for human alpha TTP predicts 278 amino acids with a calculated molecular mass of 31,749, and the sequence exhibits 94% similarity with rat alpha TTP at the amino acid level. The recombinant human alpha TTP expressed in Escherichia coli exhibits both alpha-tocopherol transfer activity in an in vitro assay and cross-reactivity to the anti-(rat alpha TTP) monoclonal antibody. Northern blot analysis revealed that human alpha TTP is expressed in the liver like rat alpha TTP. The human and rat alpha TTPs show structural similarity with other apparently unrelated lipid-binding/transfer proteins, i.e. retinaldehyde-binding protein present in retina, and yeast SEC14 protein, which possesses phosphatidylinositol/phosphatidylcholine transfer activity. Both Southern-blot hybridization of human-hamster somatic cell hybrid lines and fluorescence in situ hybridization revealed a single alpha TTP gene corresponding to the 8q13.1-13.3 region of chromosome 8, which is identical to the locus of a recently described clinical disorder, ataxia with selective vitamin E deficiency (AVED). The relationship between alpha TTP and AVED will be discussed. PMID- 7887898 TI - Control of inositol 1,4,5-trisphosphate-induced Ca2+ release by cytosolic Ca2+. AB - The synergistic action of cytosolic Ca2+ and inositol 1,4,5-trisphosphate (InsP3) in releasing intracellular Ca2+ stores has been suggested to be responsible for the complex intracellular Ca2 signals observed during hormonal stimulation of many cell types. However, the ability of cytosolic Ca2+ to potentiate Ca2+ release has recently been questioned because of the observed inhibitory effects of Ca2+ chelators used in previous studies. In the present study, EGTA and BAPTA [1,2-bis-(2-amino-phenoxy)ethane- NNN'N'-tetra-acetic acid] poorly inhibited InsP3-induced Ca2+ release from permeabilized A7r5 smooth-muscle cells. Additionally, stimulatory effects of cytosolic and luminal Ca2+ were observed either in the complete absence of Ca2+ chelator or at constant Ca(2+)-free chelator concentration. These data suggest that potentiation of InsP3-induced Ca2+ release by Ca2+ in A7r5 cells reflects an interaction between Ca2+ and InsP3 receptors, rather than a decrease in chelator-dependent inhibition. The EC50 for activation of InsP3-induced Ca2+ release by cytosolic Ca2+ was unaffected by ATP, or by changing InsP3 concentration, although InsP3-induced Ca2+ release became less sensitive to the inhibitory effects of cytosolic Ca2+ as the InsP3 concentration was elevated. Increasing H+ or Mg2+ concentration shifted the Ca(2+)-activation curve towards higher Ca2+ concentrations. These data suggest that, in addition to the InsP3-binding site, the affinity of the Ca(2+)-binding site(s) on InsP3 receptors can be modulated by intracellular cations. PMID- 7887899 TI - Promotion of binding of von Willebrand factor to platelet glycoprotein Ib by dimers of ristocetin. AB - In the absence of high shear forces, the in vitro binding of human von Willebrand factor (vWF) to its platelet receptor glycoprotein Ib (GPIb) can be promoted by two well-characterized mediators, botrocetin and ristocetin. Using purified vWF and GPIb, we have investigated the mechanisms by which ristocetin mediates this binding. Specific binding of vWF monomers to GPIb occurred with a 1:1 stoichiometry, but high-affinity binding required the participation of two ristocetin dimers. Binding was strongly dependent on pH and inhibited by low poly L-lysine concentrations, indicating ristocetin-dependent charge neutralization during the interaction. With increasing ristocetin concentrations, vWF binding depended progressively less on the involvement of its A1 loop, which is compatible with a model in which the two ristocetin dimers bridge the vWF-GPIb complex on secondary sites. In agreement with this model, the ristocetin-dimer promoted stabilization of vWF on GPIb was abolished by low concentrations of poly(Pro-Gly-Pro), which is known to complex ristocetin dimers. Mechanistic analysis of the inhibition of vWF binding by the recombinant vWF fragment Leu504 Ser728 (VCL), which covers the entire A1 loop, revealed an affinity of VCL for GPIb comparable with that of the botrocetin-vWF complex for GPIb, and identified a specific but 20-fold lower affinity of VCL in the presence of ristocetin. The proline-rich peptides flanking the vWF A1 loop, Cys474-Val489 and Leu694-Asp709, inhibited vWF binding semispecifically by competitively interfering with the formation of the GPIb-vWF complex rather than by complexation of free ristocetin dimers. In conclusion, ristocetin-promoted binding of vWF to its GPIb receptor results from charge neutralization and interactions involving proline residues in the vicinity of the natural interaction sites present on both GPIb and the A1 domain of vWF. PMID- 7887900 TI - Two sequences flanking the major autophosphorylation site of the insulin receptor are essential for tyrosine kinase activation. AB - The tyrosine kinase domain of the human insulin receptor (IR) contains several short amino acid motifs which are strictly conserved in all protein kinases and two sequence motifs which are specific to the tyrosine kinases (AAR or RAA and P(I)/VK/RWT/M). In the serine/threonine kinases these motifs are replaced by the sequences KPE and GT/SXXY/PX respectively. In the present work, the tyrosine kinase-specific sequences of the IR (1134AAR1136 and 1172PVRWM1176) were replaced using site-directed mutagenesis by sequences which confer a serine kinase specificity on the receptor. Five different IR mutants were expressed in Chinese hamster ovary (CHO) or COS cells and their structural and functional properties compared with those of the wild-type recombinant human IR. These mutants are processed normally and bind insulin with normal affinities. None of the mutants containing a putative serine kinase-specific sequence display detectable autophosphorylation or tyrosine kinase activity in response to insulin, either in vitro or in vivo. These mutants were also unable to phosphorylate serine/threonine kinase substrates after insulin stimulation. Unexpectedly, they showed impaired ATP binding, as studied by an original technique consisting of cross-linking adenosine 5'-([35S]thio)triphosphate to partially purified receptors. Finally, none of the studied mutants transmit the insulin signal necessary to stimulate either DNA or glycogen synthesis. These data provide evidence for the importance of these conserved sequences in the kinase domain for both receptor activation and kinase activity. Furthermore, they demonstrate that the exchange of sequences specific to the catalytic domain of tyrosine kinases for those specific to the serine/threonine kinases is not sufficient to confer serine/threonine specificity on the insulin receptor. PMID- 7887901 TI - Identification and characterization of DNA elements implicated in the regulation of CYP4A1 transcription. AB - We have identified a peroxisome proliferator response element (PPRE) approx. 4300 nucleotide upstream of the rat cytochrome P-450 CYP4A1 gene. Two members of the steroid-hormone-receptor superfamily, the peroxisome proliferator-activated receptor-alpha (PPAR alpha) and the retinoid X receptor-alpha (RXR alpha), bind specifically to this element as a heterodimer, and this element confers responsiveness to the peroxisome proliferator Wyeth-14,643 when tested in co transfection assays. A second element, located 35 nucleotides further upstream, fails to bind PPAR alpha/RXR alpha heterodimers and is unresponsive to Wy-14,643 in co-transfection assays. Both elements are, however, responsive to 9-cis retinoic acid in the presence of RXR alpha, when tested in the co-transfection assay. As RXR alpha fails to bind to either element as a homodimer, we suggest that RXR alpha interacts with PPAR alpha to regulate transcription via the proximal element, and interacts with some other cellular factor to regulate transcription via the more distal element. This is consistent with previous reports that a number of peroxisome proliferator-regulated genes contain PPRE like elements as part of their regulatory sequences, which may be recognized by several receptor combinations. This provides further evidence that PPARs and their co-factors are important in mediating the pleiotropic action of peroxisome proliferators. PMID- 7887902 TI - Variations in in vivo phosphorylation at the proline-rich domain of the microtubule-associated protein 2 (MAP2) during rat brain development. AB - Microtubule-associated protein 2 (MAP2) is an in vitro substrate for MAP kinase. Part of the phosphorylation occurs at the C-terminal microtubule-binding domain of the molecule which contains a cluster of putative consensus sites for MAP kinase on a proline-rich region. A peptide with the sequence RTPGTPG-TPSY, located at this region of the molecule, is efficiently phosphorylated by MAP kinase in vitro. An antibody (972) raised against this non-phosphorylated peptide has been used to test for in vivo phosphorylation at the proline-rich domain of the MAP2 molecule. The reaction of purified MAP2 with antibody 972 diminishes after in vitro phosphorylation by MAP kinase and is enhanced after in vitro dephosphorylation by alkaline phosphatase. A fraction of brain MAP2 isolated by iron-chelation affinity chromatography appears to be phosphorylated in vivo at the site recognized by antibody 972. There is some variation in the phosphorylation of MAP2 at the proline-rich region throughout rat brain development. MAP2C is more highly phosphorylated in the developing rat brain, whereas high-molecular-mass MAP2 is more extensively phosphorylated in the adult rat brain. PMID- 7887903 TI - Cell-shape-dependent modulation of p52(PAI-1) gene expression involves a secondary response pathway. AB - Expression of the rat p52(PAI-1) gene is positively regulated by agents that influence cellular microfilament organization and/or cell-to-substrate adhesion [e.g. cytochalasin D (CD) and sodium n-butyrate (NaB)] [Higgins, Chaudhari and Ryan (1991) Biochem. J. 273, 651-658; Higgins, Ryan and Providence (1994) J. Cell. Physiol. 159, 187-195]. As shape-responsive genes may be subject to inducer specific controls, the biochemical mechanisms underlying the shape-dependent pathway of p52(PAI-1) gene regulation were examined in v-ras-transformed rat kidney (KNRK) cells. NaB and/or CD effectively stimulated p52(PAI-1) run-off transcription and augmented de novo p52(PAI-1) mRNA and protein synthesis in KNRK cells; induction at both the mRNA and protein levels was inhibited by actinomycin D. Pretreatment with cycloheximide (CX) markedly attenuated NaB- and/or CD stimulated p52(PAI-1) expression. CX alone, however, induced low levels of p52(PAI-1) mRNA; increased p52(PAI-1) protein synthesis was evident after release of KNRK cells from CX blockade. Such CX-mediated induction was also sensitive to actinomycin D. Full stimulation of p52(PAI-1) expression in KNRK cells in response to the shape modulators NaB and/or CD involves transcriptional activation of the p52(PAI-1) gene, requires de novo RNA synthesis and occurs through a secondary-response (i.e. protein-synthesis-dependent) pathway. PMID- 7887904 TI - Probing the functional role of the N-terminal region of cystatins by equilibrium and kinetic studies of the binding of Gly-11 variants of recombinant human cystatin C to target proteinases. AB - The interaction between cystatin C variants, in which the evolutionarily conserved Gly-11 residue was substituted by Ala, Glu or Trp, and the cysteine proteinases, papain, ficin, actinidin and cathepsin B, was characterized. The substitutions reduced the affinity of binding in a manner consistent with the Gly residue of the wild-type inhibitor, allowing the N-terminal region to adopt a conformation that was optimal for interaction with target proteinases. Replacement of Gly-11 by Ala resulted in only a 5- to 100-fold reduction in binding affinity. Comparison with the affinities of wild-type cystatin C lacking the N-terminal region indicated that even this small structural change affects the conformation of this region sufficiently to largely abolish its interaction with the weakly binding proteinases, actinidin and cathepsin B. However, the substitution allows interactions of appreciable strength between the N-terminal region and the tightly binding enzymes, papain or ficin. Replacement of Gly-11 with the larger Glu and Trp residues substantially decreased the affinity of binding to all enzymes, from 10(3)- to 10(5)-fold. These substitutions further affect the conformation of the N-terminal region, so that interactions of this region with papain and ficin are also essentially eliminated. The decreased affinities of the three cystatin C variants for papain, ficin and actinidin were due exclusively to increased dissociation rate constants. In contrast, the decreased affinity between cathepsin B and the Ala-11 variant, the only one for which rate constants could be determined with this enzyme, was due almost entirely to a decreased association rate constant. This behaviour is analogous to that observed for forms of cystatin C lacking the N-terminal region and supports the conclusion that the mode of interaction of this region with target proteinases varies with the enzyme as a result of structural differences in the active-site region of the latter. PMID- 7887905 TI - IgM monoclonal antibodies recognizing Fc alpha R but not Fc gamma RIII trigger a respiratory burst in neutrophils although both trigger an increase in intracellular calcium levels and degranulation. AB - The role of IgG receptor, Fc gamma RIII, in the triggering of neutrophil functions has been controversial. Here we show that IgM monoclonal antibodies, Leu 11b and 1D3, recognizing Fc gamma RIII, bind to human neutrophils triggering an increase in intracellular calcium concentration and release of myeloperoxidase upon degranulation but do not trigger a respiratory burst detectable as lucigenin enhanced chemiluminescence. Although many fewer molecules of IgM monoclonal antibody, MY43, recognizing Fc alpha R, bind to the same cells they trigger a much greater increase in intracellular calcium concentration, release of myeloperoxidase and a strong respiratory burst. Since the respiratory bursts triggered by IgG and IgA are equivalent, this demonstrates that Fc gamma RII is responsible for the IgG-mediated response. IgM monoclonal antibody MC2, recognizing the abundant neutrophil cell-surface carbohydrate CD15, also triggers a small rise in intracellular calcium but no respiratory burst. PMID- 7887906 TI - Analysis of the relative interactions between the alpha 2C10 adrenoceptor and the guanine-nucleotide-binding proteins G(o)1 alpha and Gi 2 alpha following co expression of these polypeptides in rat 1 fibroblasts. AB - Rat 1 fibroblasts which had been transfected to express the human alpha 2C10 adrenoceptor (clone 1C) were further co-transfected with a plasmid containing the hygromycin-B-resistance gene and a plasmid containing a cDNA encoding the alpha subunit of the rat pertussis-toxin-sensitive G-protein G(o)1. In clone 3 the receptor was expressed at some 2.2 pmol/mg of membrane protein, and G(o)1 alpha at approx. 100 pmol/mg of membrane protein. The interaction of these two polypeptides and that between the receptor and Gi2 alpha (endogenously expressed at some 50 pmol/mg of membrane protein) were studied. Agonist activation of G(o)1 alpha was observed in membranes of the alpha 2C10-adrenoceptor(+)-G(o)1 alpha+ cells (clone 3), but not in alpha 2C10-adrenoceptor(+)-G(o)alpha-cells (clone 1C), whereas similar agonist-dependent activation of Gi2 alpha was observed in both cell types. alpha 2C10-adrenoceptor activation of G(o)1 alpha and Gi2 alpha in clone-3 membranes was produced with similar agonist-dose-effect curves. These observations indicate that the receptor interacts with equivalent affinity with each of these G-proteins. Agonist-dependent cholera-toxin-catalysed [32P]ADP ribosylation of G(o)1 alpha was terminated when the alpha 2-adrenoceptor antagonist yohimbine was added subsequent to agonist-induced initiation of the reaction and release of GDP, demonstrating the conformational requirement for this reaction to be the ternary complex of agonist-occupied receptor and guanine nucleotide-denuded G-protein. PMID- 7887907 TI - Effect of magnetic field strength on the linewidth and spin-lattice relaxation time of the thiocyanate carbon of cyanylated beta-lactoglobulin B: optimization of the experimental parameters for observing thiocyanate carbons in proteins. AB - The linewidths and spin-lattice relaxation times of the 13C-n.m.r. signal at 109.7 p.p.m. due to the thiocyanate carbon of intact [cyanato-13C]cyanylated-beta lactoglobulin-B have been determined at magnetic field strengths of 1.88, 6.34 and 11.74 T as well as the spin-lattice relaxation times of its backbone alpha carbon atoms. The linewidths were directly proportional to the square of the magnetic field strength and we conclude that, at magnetic field strengths of 6.34 T or above, more than 70% of the linewidth will be determined by chemical-shift anisotropy. We estimate that the spin-lattice relaxation time resulting from the chemical-shift anisotropy of the thiocyanate carbon is 1.52 +/- 0.1 s and we conclude that for magnetic field strengths of 6.34 T and above the observed spin lattice relaxation time of the thiocyanate carbon will be essentially independent of magnetic field strength. Using the rigid-rotor model we obtain estimates of the rotational correlation time of [cyanato-13C]cyanylated-beta-lactoglobulin-B and of the chemical-shift anisotropy shielding tensor of its thiocyanate carbon. We have calculated the linewidths and spin-lattice relaxation times of thiocyanate carbons at magnetic field strengths of 1.88-14.1 T in proteins with M(r) values in the range 10,000-400,000. The effects of magnetic field strength on the resolution and signal-to-noise ratios of the signals due to thiocyanate carbons attached to proteins of M(r) greater than 10,000 are discussed. PMID- 7887908 TI - Cause of spectral variation in the luminescence of semisynthetic aequorins. AB - Aequorin emits light in the presence of Ca2+, decomposing into apoaequorin, coelenteramide and CO2. Semisynthetic aequorins, produced by replacing the coelenterazine moiety in aequorin with analogues of coelenterazine, showed widely different sensitivities to Ca2+ as well as certain spectral variations. A group of semisynthetic aequorins, e-type aequorins, showed bimodal luminescence, with peaks at 400-405 nm and 440-475 nm in various intensity ratios, whereas all other aequorins luminesced with only one peak, in the range 440-475 nm. The cause of the spectral variation was studied by various experiments including: (1) comparison with the fluorescence of the spent solution and the luminescence of the spent solution produced by added coelenterazine; (2) luminescence in 2H2O; (3) the rate of conformational change of apoaequorin; (4) the rates of regeneration in the presence and absence of O2. The results suggested that the spectrum of Ca(2+)-triggered luminescence is strongly affected by the ionic charge on the amide N atom of the coelenteramide that is bound to apoaequorin. When the amide N atom is negatively charged, light is emitted with a 440-475 nm peak. In the case of e-type aequorins, the negative charge on the amide N atom is less because of the structure of e-coelenterazine involved, resulting in the emission of a 400-405 nm peak from the uncharged form of coelenteramide; the intensity ratio of 400-405 nm peak to 440-475 nm peak is determined by the amount of negative charge resting on the amide N atom of e-coelenteramide at the time of light emission. Most of the spectral variations in luminescence and fluorescence can be explained on the basis of ionic and hydrophobic interaction between a coelenteramide and apoaequorin. PMID- 7887909 TI - Mechanism of ligand binding to alpha 1-acid glycoprotein (orosomucoid): correlated thermodynamic factors and molecular parameters of polarity. AB - Eight ligands were used in this study, four basic, three neutral and one acidic. Their binding to serum alpha 1-acid glycoprotein (orosomucoid) was measured at several temperatures, and the data were analysed together by a general model with three unknowns, number of binding sites, delta H0 and delta S0. The partition coefficients of the ligands were measured in octanol/water and heptane/water systems (log Poct. and log Phep.), and their molecular volumes were calculated by molecular modelling techniques. These structural properties allow determination of polarity parameters (delta log Poct.-hep., lambda oct. and lambda hep.) which encode in different proportions the various polar interactions between the solute and the aqueous and organic phases, i.e. hydrogen-bonding capacity and dipolarity/polarizability. This study shows that good correlations exist between delta H0 or delta S0 and polarity parameters, such that the enthalpic contribution to binding increases with increasing polarity of the ligands, mainly hydrogen-bond-donor acidity, whereas their entropic contribution to binding decreases. PMID- 7887910 TI - S100 beta is a target protein of neurocalcin delta, an abundant isoform in glial cells. AB - To clarify the function of neurocalcin delta, an isoform found abundantly in glial cells, we attempted to find its target proteins by using neurocalcin delta affinity chromatography and the 125I-neurocalcin delta gel-overlay method. The 10, 14, 27, 36 and 50 kDa bands found on SDS/PAGE bound to 125I-neurocalcin delta, and 10, 11, 19, 24, 26, 50 and 70 kDa proteins were eluted from a neurocalcin delta-affinity column in a Ca(2+)-dependent manner. Sequence analysis of proteolytic peptides revealed the following identities: S100 beta (10 kDa), S100 alpha (11 kDa), myelin basic protein (19 kDa), glyceraldehyde-3-phosphate dehydrogenase (36 kDa) and tubulin beta-chain (50 kDa). A zero-length cross linking study indicated that 1 mol of S100 beta bound to 1 mol of neurocalcin delta. With the gel-overlay method, purified S100 beta protein and calcyclin bound to 125I-neurocalcin delta whereas calgizarrin and calvasculin, other members of the S100 family, did not. These findings suggest that S100 beta is one of the target proteins of neurocalcin delta, and the neurocalcin delta-S100 beta complex may be involved in Ca(2+)-signalling in the glial cell. PMID- 7887911 TI - Inositol 1,2,3-trisphosphate and inositol 1,2- and/or 2,3-bisphosphate are normal constituents of mammalian cells. AB - 1. An inositol trisphosphate (InsP3) distinct from Ins(1,4,5)P3 and Ins(1,3,4)P3, which we previously observed in myeloid and lymphoid cells [French, Bunce, Stephens, Lord, McConnell, Brown, Creba and Michell (1991) Proc R. Soc. London B 245, 193-201; Bunce, French, Allen, Mountford, Moore, Greaves, Michell and Brown (1993) Biochem. J. 289, 667-673], is present in WRK1 rat mammary tumour cells and pancreatic endocrine beta-cells. 2. It has been identified as Ins(1,2,3)P3 by a combination of oxidation to ribitol, a structurally diagnostic polyol, and ammoniacal hydrolysis to identified inositol monophosphates. 3. Ins(1,2,3)P3 concentration in HL60 cells changed little during stimulation by ATP or fMetLeuPhe or during neutrophilic or monocytic differentiation, and Ins(1,2,3)P3 was unresponsive to vasopressin in WRK1 cells. 4. Ins(1,2,3)P3 was usually more abundant than Ins(1,4,5)P3, often being present at concentrations between approximately 1 microM and approximately 10 microM. 5. HL60, WRK-1 and lymphoid cells also contain Ins(1,2)P2 or Ins(2,3)P2, or a mixture of these two enantiomers, as a major InsP2 species. 6. Ins(1,2,3)P3 and Ins(1,2)P2/Ins(2,3)P2 are readily detected in cells labelled for long periods, but not in acutely labelled cells. This behaviour resembles that of InsP6, the most abundant cellular inositol polyphosphate that includes the 1,2,3-trisphosphate motif, which also achieves isotopic equilibrium with inositol only slowly. 7. Ins(1,2,3)P3 is the major InsP3 that accumulates during metabolism of InsP6 by WRK-1 cell homogenates. 8. Possible metabolic relationships between Ins(1,2,3)P3, Ins(1,2)P2/Ins(2,3)P2 and other inositol polyphosphates in cells, and a possible role for Ins(1,2,3)P3 in cellular iron handling, are considered. PMID- 7887912 TI - Forward and reverse catalysis and product sequestration by human glutathione S transferases in the reaction of GSH with dietary aralkyl isothiocyanates. AB - The reversible reaction of GSH with two dietary anticarcinogens, benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC), has been studied in the absence and presence of human glutathione S-transferases (GSTs). The spontaneous reaction at pH 7.4 and 37 degrees C yielded values for k2 of 17.9 and 6.0 M-1.s-1 for GSH conjugation of BITC and PEITC respectively (forward reaction), and k1 values of 6.9 x 10(-4) and 2.4 x 10(-4) s-1 for dissociation of the respective GSH conjugates, BITC-SG and PEITC-SG (reverse reaction). GSTs A1 1, A2-2, M1a-1a and P1-1 catalysed both the forward and reverse reactions with specific activities (mumol/min per mg at 30 microM isothiocyanate or GSH conjugate) ranging from 23.1 for the GSH conjugation of BITC by GST P1-1 to 0.03 for the dissociation of BITC-SG by GST A1-1. When present at similar concentration to substrates (12 microM), GSTs A1-1 and A2-2 but not GST M1a-1a shifted the equilibrium in favour of BITC-SG or PEITC-SG. Kinetic studies confirmed that GST A1-1 interacted selectively with the GSH conjugates in the micromolar range (Km 6.9 microM, Ki 4.3 microM), whereas GST M1a-1a interacted with BITC-SG and PEITC-SG with approx. 5-fold lower affinity. In conclusion, GSTs are true catalysts; at high intracellular concentration they also sequester GSH conjugates, promoting GSH conjugation, whereas trace extracellular GSTs promote dissociation of effluxed organic isothiocyanate-GSH conjugates. PMID- 7887913 TI - Strictosidine synthase from Catharanthus roseus: purification and characterization of multiple forms. AB - Multiple (six) forms of strictosidine synthase from Catharanthus roseus cell suspension cultures were purified and characterized. A purification protocol is presented composed of hydrophobic-interaction, gel-permeation and ion-exchange chromatography and chromatofocusing. Four of six isoforms were purified to apparent homogeneity, whereas two others were nearly homogeneous. All strictosidine synthase isoforms were found to be glycoproteins. The isoforms were also found in leaves and roots of the plant, in seedlings and in hairy root cultures. The ratio of the different isoforms differed slightly between these sources. The kinetic parameters of the isoforms showed no significant differences. The maximal velocity (300-400 nkat/mg of protein) is the highest reported so far. It was demonstrated that the apparent Michaelis constant for tryptamine (approx. 9 microM) is much lower than values reported previously. The presence of weak product inhibition (Kp approx. 35 times Km) was established, whereas substrate inhibition was not detected. PMID- 7887914 TI - Differential regulation of glutathione peroxidase by selenomethionine and hyperoxia in endothelial cells. AB - We have studied the effect of selenomethionine (SeMet) and hyperoxia on the expression of glutathione peroxidase (GP) in human umbilical vein endothelial cells. Incubation of HUVEC with 1 x 10(-6) M SeMet for 24 h and 48 h caused a 65% and 86% increase in GP activity respectively. The same treatment did not result in significant changes in GP gene transcription and mRNA levels. Pactamycin, a specific inhibitor of the initiation step of translation, prevented the rise in GP activity induced by SeMet and caused an increase in GP mRNA in both cells grown in normal and SeMet-supplemented medium. Interestingly, SeMet supplementation stimulated the recruitment of GP mRNA from an untranslatable pool on to polyribosomes, so that the concentration of GP mRNA in polyribosomal translatable pools was 50% higher in cells grown in SeMet-supplemented medium than in cells grown in normal medium. On the other hand, cells exposed to 95% O2 for 3 days in normal medium showed a 60%, 394% and 81% increase in GP gene transcription rate, mRNA levels and activity respectively. Hyperoxia also stabilized GP mRNA. Hyperoxic cells grown in SeMet-supplemented medium did not show any change in GP gene transcription and mRNA levels, but expressed an 81% and 100% increase in GP activity and amount of GP mRNA associated with polyribosomes respectively, when compared with hyperoxic cells maintained in normal medium. Thus, GP appeared to be regulated post-transcriptionally, most probably co-translationally, in response to selenium availability, and transcriptionally and post-transcriptionally in response to oxygen. PMID- 7887915 TI - Expression of recombinant human phenylalanine hydroxylase as fusion protein in Escherichia coli circumvents proteolytic degradation by host cell proteases. Isolation and characterization of the wild-type enzyme. AB - Recombinant human phenylalanine hydroxylase (hPAH) was produced in high yields in Escherichia coli using the pET and pMAL expression vectors. In the pMAL system, hPAH was fused through the target sequences of the restriction protease factor Xa (IEGR) or enterokinase (D4K) to the C-terminal end of the highly expressed E. coli maltose-binding protein (MBP). The recombinant hPAH, recovered in soluble forms, revealed a high specific activity even in crude extracts and was detected as a homogeneous band by Western-blot analysis using affinity-purified polyclonal rabbit anti-(rat PAH) antibodies. The enzyme expressed in the pET system was subject to limited proteolysis by host cell proteases and was difficult to purify with a satisfactory yield. By contrast, when expressed as a fusion protein in the pMAL system, hPAH was resistant to cleavage by host cell proteases and was conveniently purified by affinity chromatography on an amylose resin. Catalytically active tetramer-dimer (in equilibrium) forms of the fusion protein were separated from inactive, aggregated forms by size-exclusion h.p.l.c. After cleavage by restriction protease, factor Xa or enterokinase, hPAH was separated from uncleaved fusion protein, MBP and restriction proteases by hydroxylapatite or ion-exchange (DEAE) chromatography. The yield of highly purified hPAH was approx. 10 mg/l of culture. The specific activity of the isolated recombinant enzyme was high (i.e. 1440 nmol of tyrosine.min-1.mg-1 with tetrahydrobiopterin as the cofactor) and its catalytic and physicochemical properties are essentially the same as those reported for the enzyme isolated from human liver. The recombinant enzyme, both as a fusion protein and as purified full-length hPAH, was phosphorylated in vitro by the catalytic subunit of cyclic AMP-dependent protein kinase. The phosphorylated from of hPAH electrophoretically displayed an apparently higher molecular mass (approximately 51 kDa) than the non phosphorylated (approximately 50 kDa) form. PMID- 7887916 TI - Calcium mobilization and protein kinase C activation are required for cholecystokinin stimulation of pancreatic cholesterol esterase secretion. AB - The bile salt-stimulated cholesterol esterase is a digestive enzyme synthesized by the acinar cells of the pancreas. Previous results have shown that cholesterol esterase biosynthesis and secretion in the AR42J pancreatoma cells could be increased 3-5-fold by intestinal hormones such as cholecystokinin (CCK). The purpose of the current study is to explore the signalling mechanism by which CCK stimulation of AR42J cells results in increased biosynthesis and secretion of the cholesterol esterase. The results showed that the CCK-induced cholesterol esterase secretion could be mimicked by addition of the Ca2+ ionophore A23187 or by transient incubation of AR42J cells with the protein kinase C activator phorbol 12-myristate 13-acetate (PMA). Cholesterol esterase stimulation by CCK, A23187 and PMA could be abolished by the calcium chelator BAPTA or by specific protein kinase C inhibitors such as chelerythrine. Additionally, prolonged incubation of AR42J cells with PMA to reduce the protein kinase C level, also reduced CCK-stimulated cholesterol esterase secretion to a level similar to that observed in control cells. Taken together, these data suggested that CCK activation of cholesterol esterase secretion may be mediated by a Ca(2+) dependent protein kinase C pathway, requiring increases in calcium mobilization and activation of protein kinase C. PMID- 7887917 TI - The heparin binding site of follistatin is involved in its interaction with activin. AB - Whether the heparin-binding site of follistatin would interact with activin has been examined. When a mixture of recombinant human follistatin-288 (rhFS-288) and -315 (rhFS-315) was applied to an activin-coupled affinity column, followed by stepwise elution of the column using 4M urea, 8M urea, 1M guanidine-HCl and 2M guanidine-HCl, rhFS-315 was eluted with 4M urea, while rhFS-288 was eluted with 2M guanidine-HCl. This finding implies that the carboxylterminal 27 amino acid extension of rhFS-315, which is not present in rhFS-288, affects the binding of follistatin with activin. Addition of heparin (50 micrograms/ml) to the elution solvent caused rhFS-288 to elute with 4M urea, whereas rhFS-315 was not affected. These data suggest for the first time that these two structurally related follistatin molecules interact with activin by different modes of binding and, in the presence of heparin, the interaction of rhFS-288 with activin is indistinguishable from that of rhFS-315. Two analogs of rhFS-288 mutated at the heparin binding site were eluted with 8M urea or 1M guanidine-HCl, distinct from the elution profile of the intact rhFS-288. These results indicated that mutation at the heparin binding site alters the activin binding affinity. In addition, bioassay of the two mutants showed that they were less potent than the rhFS-288. These findings suggest that the heparin binding site of follistatin also contributes to its binding for activin, and heparin may play an important role in the bioactivity of follistatin. PMID- 7887918 TI - Phosphorylation of the adenomatous polyposis coli protein and its possible regulatory effects in cells. AB - The adenomatous polyposis coli (APC) gene is etiologically associated with familial adenomatous polyposis and gastrointestinal malignancies, but its cellular function and role in tumorigenesis are unclear. Recent reports indicate that wild-type, but not mutant, APC gene product (APC) is associated with and promotes the assembly of cytoskeletal microtubules in vitro, suggesting that this mechanism has importance in tumor development. Because other microtubule associated proteins (MAPs) undergo phosphorylation in their normal functioning, we postulated that APC is a phosphoprotein. HCT116 cells, containing full-length APC protein, were [32P]-prelabeled, and a 300-kDa band corresponding to phosphorylated APC was immunoprecipitated using each of three different anti-APC antibodies. High voltage electrophoresis of [32P]-labeled APC showed the presence of phospho-serine and phospho-threonine residues. Further immunoprecipitation analyses showed phosphorylation of i) full-length APC in human lymphoblastoid cells and ii) carboxyl-truncated APC in SW480 and DiFi colon carcinoma cells. Thus, APC is probably a phosphoprotein in normal and malignant tissues. We hypothesize a mechanism whereby phosphorylation of APC may play a regulatory role in its interaction with microtubules. This may involve phosphorylation of (Ser/Thr)-Pro amino acid motifs in APC's basic domain. We propose that deletion of this domain disrupts APC binding to microtubules, explaining how APC mutations are linked to cancer development. PMID- 7887919 TI - Fluorescence quenching in membrane phase. AB - Membrane-related events can be investigated when the fluorescence of an intramembrane fluorophore is quenched by molecules that are dissolved in lipid phase. In this case the bimolecular quenching constant characterises the relative transport rate of the fluorophore and quencher molecules in the membrane interior and thereby it is related to the dynamics or structure of the membrane. Unlike classic quenching experiments, the crucial point in such studies is that the concentration of the quencher in the lipid phase differs from that in the bulk. As a consequence, it is usually described by different models, or regarded as the total concentration added. Here a simple fluorometric study is presented for distinguishing between the solvation mechanisms (partition or binding) of quencher molecules in membrane phase. PMID- 7887920 TI - Temperature acclimation induces light meromyosin isoforms with different primary structures in carp fast skeletal muscle. AB - Carp acclimated to 10 degrees C gave 69k, 66k, and 62kDa light meromyosin (LMM) fragments in SDS-PAGE, while fish acclimated to 30 degrees C gave 74k, 69k, 66k, and 62kDa fragments. The microsequence analysis revealed that the 69k and 66kDa components from the 10 degrees C-acclimated carp contained an N-terminal amino acid sequence different from that of 62kDa. The four fragments from the 30 degrees C-acclimated carp showed the same sequence as that of the 69k and 66kDa components from the 10 degrees C-acclimated carp, except that the 2nd amino acid, Ala, of the 10 degrees C-acclimated LMM was replaced by Thr. DNA fragments encoding an N-terminal region of LMM were amplified by PCR or reverse transcriptase-PCR, demonstrating that the two acclimated groups further contained several amino acids substituted. PMID- 7887921 TI - Trimeric G protein alpha subunits of the Gs and Gi families localized at the Golgi membrane. AB - The occurrence of individual G proteins within Golgi membranes from liver and from adrenal medulla were analyzed by Western blotting. Two splice variants of G alpha s and also G alpha i-3 were found in both tissues. Additionally, G alpha i 2, its 43-kDa splice variant and G alpha o were strongly labeled in Golgi of adrenal medulla. Golgi preparations of liver contained comparable quantities of G alpha i-2 and a second variant of 46 kDa, but no G alpha o was detected. Immunoelectron microscopic studies of the above Golgi preparations showed that both G alpha i-2 and G alpha i-3 are localized at multivesicular structures identified as Golgi complexes. The occurrence of two stimulatory G proteins (G alpha s-S and G alpha s-L) and three or four alpha subunits of the Gi/Go type as components of the Golgi membrane support the notion that formation of different vesicle types might be regulated by individual stimulatory and inhibitory G proteins. PMID- 7887922 TI - Possible involvement of the Ah receptor in the induction of cytochrome P-450IA1 under conditions of hydrodynamic shear in microcarrier-attached hepatoma cell lines. AB - The exposure of two hepatoma cell lines, Hep G2 and Hepa-1, to moderate hydrodynamic shear, in microcarrier-attached suspension cultures, resulted in the transient induction of cytochrome P450IA1 (CYP1A1). Both cell lines have been characterized with respect to their Ah receptor (AhR) concentrations and induce CYP1A1 in response to exposure to xenobiotics such as 2,3,7,8-tetrachlorodibenzo p-dioxin (TCDD). Using an AhR antagonist, alpha-naphthoflavone (alpha-NF) and a protein kinase C (PKC) inhibitor, staurosporine (ST), in the Hep G2 cell line, the induced CYP1A1 activity was modulated in the same manner as when the cells were coexposed to TCDD and either alpha-NF or ST. Exposure of the Hep G2 cell line to TCDD and shear resulted in both enhancement of the induced CYP1A1 activity in addition to a competitive response. Finally, using the wild type and AhR defective Hepa-1 cell lines, it was demonstrated that a functional AhR was required for shear-induced CYP1A1 expression. The data obtained in the three cell lines indicate a role for the AhR in the induction of CYP1A1 by shear in agitated microcarrier cultures. PMID- 7887923 TI - DNA binding proteins that amplify surfactant protein B gene expression: isolation and characterization. AB - We identified and characterized two proteins that bind the promoter of surfactant protein B (SP-B) and affect its expression. Proteins A2 and B were identified and their cDNAs cloned and sequenced. Both were novel. They bound a 212-bp functional promoter region at an NF1 site, located between -184 and -198. Effects of these DNAbp on SP-B promoter activity were studied by contransfecting a reporter construct of this 212-bp sequence + luciferase, together with expression constructs for A2 and B into H441 cells. Alone, A2 and B expression elicited modest but statistically significant increases in SP-B promoter activity. When dexamethasone was added, B further increased SP-B promoter activity. For SP-B, basal expression and glucocorticoid responsiveness may involve a number of hitherto unknown gene activators. PMID- 7887924 TI - Elucidation of antioxidant activity of alpha-lipoic acid toward hydroxyl radical. AB - The photosensitive organic hydroperoxide, NP-III, which produces hydroxyl radicals on illumination by UVA light, was used to examine the antioxidant activity of alpha-lipoic acid and its derivatives toward hydroxyl radical. Apolipoprotein (apo-B) of human low density lipoprotein (LDL) and bovine serum alubumin (BSA) were irradiated with UVA in the presence of NP-III and alpha lipoic acid. The oxidation of BSA and the apo-B protein of LDL by NP-III was completely suppressed by alpha-lipoic acid. ESR studies using dimethylpyrroline oxide (DMPO) as a spin trapping reagent also revealed that in the presence of alpha-lipoic acid, the DMPO-OH adduct produced from the irradiation of NP-III and DMPO completely disappeared. DMPO-OH quenching experiments were performed in the presence or absence of desferoxamine but no change in the signal intensity was found. Hence, the quenching activity of alpha-lipoic acid is not due to its chelating activity toward transition metals (ferrous ions). The results lead us to conclude that alpha-lipoic acid is an efficient hydroxyl radical quencher owing to the disulfide bond in the dithiolane ring. PMID- 7887925 TI - RNA cleavage by C-1027 chromophore, an enediyne antitumor antibiotic: high selectivity to an anticodon arm. AB - This study demonstrates unique reactivity of the C-1027 chromophore toward a tRNA(phe). In the presence of Mg2+ ions where the tRNA(phe) attains a stable three-dimensional structure, the enediyne chromophore exhibits high cleavage selectivity to the anticodon arm. The present reactivity of the C-1027 chromophore is useful in development of new chemical probes for mapping of tertiary RNA structure. Considering the paucity of RNA repair mechanisms, RNA may be also an important biological target for certain enediyne antibiotics. PMID- 7887926 TI - Fractionation and characterization of protein C-terminal prenyl-cysteine methylesterase activities from rabbit brain. AB - Reversible carboxyl methylation of the C-terminal geranylgeranylcysteine of G25K may regulate its activity and cellular localization. Brain homogenates were examined for enzyme activities which hydrolyze the methyl ester of [3H]methyl G25K to produce [3H]methanol. Methylesterase activity was detected in both soluble and membrane fractions. The soluble activity was fractionated into at least two distinct activities. One soluble activity appears to be due to the lysosomal protease, cathepsin B, based on sensitivity to certain protease inhibitors, acidic pH optimum, size, and ability to cleave the peptide substrate N alpha-CBZ-Arg-Arg-7-amido-4-methylcoumarin. A second soluble activity, associated with a protein of approximately 25 kDa, exhibits a neutral pH optimum, insensitivity to protease inhibitors, and inhibition by the esterase inhibitor, ebelactone B. The membrane fraction contains larger amounts of a similar methylesterase that may represent the physiologically relevant form of the enzyme. PMID- 7887927 TI - Differential K+ channel distribution in smooth muscle cells isolated from the pulmonary arterial tree of the rat. AB - Intracellular photorelease of Ca2+ demonstrated the presence of Ca(2+)-activated K+ channels in smooth muscle cells isolated from different locations of the rat pulmonary arterial tree. However, cell-free patch studies revealed marked differences in K+ channel distribution. In the main pulmonary artery the most frequently observed K+ channel was a approximately 245pS conductance Ca(2+)- and ATP-activated (KCa,ATP) channel. In small pulmonary arteries two K+ channel types predominated: the KCa,ATP channel and a approximately 185pS conductance K+ channel insensitive to intracellular Ca2+, ATP and voltage. This difference in K+ channel distribution may highlight a more complex regulatory mechanism for controlling membrane potential in small pulmonary arteries, reflecting their physiologically more important role in governing pulmonary vascular reactivity. PMID- 7887928 TI - Sensitizing effect of lysophosphatidic acid on mechanoreceptor-linked response in cytosolic free Ca2+ concentration in cultured smooth muscle cells. AB - We found that lysophosphatidic acid (LPA) sensitizes response in cytosolic free Ca2+ concentration ([Ca2+]i) to mechanical stimulation in cultured longitudinal muscle cells from guinea pig ileum. [Ca2+]i was transiently increased by spritzing of bath solution onto cells as mechanical stimulation in the presence of LPA, but not in absence of LPA. The effect was reversible and concentration dependent (1-30 nM). Ga3+ but not nicardipine inhibited the [Ca2+]i transient in the presence of LPA. Phosphatidic acid also induced the sensitization, but the effective concentration was more than 10 times higher than in LPA. Histamine and carbachol did not have any sensitizing effect to mechanical stimulation. These results show that LPA sensitizes mechanoreceptor-linked response, suggesting that LPA may play an important role in mechanotransduction mechanisms as an endogenous regulatory factor. PMID- 7887929 TI - Identification of phosphatidylinositol 3,4,5-trisphosphate in pancreatic islets and insulin-secreting beta-cells. AB - The signal transduction mechanisms involved in insulin secretion by the beta-cell are poorly understood. Glucose, the main physiological secretagogue, needs to be metabolized, but the identity of the intracellular messengers which couple glucose metabolism and insulin exocytosis is controversial. We now report the identification of phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3), the end-product of phosphatidylinositol 3-kinase phosphorylation of polyphosphoinositides, in islets and in an insulin-secreting clonal beta-cell line, RINm5F, using a combination of thin layer chromatography and high performance liquid chromatography analyses and by demonstrating that sequential deacylation and deglyceration of PtdIns(3,4,5)P3 yields inositol 1,3,4,5 tetrakisphosphate. Unlike other cell types, significant levels of PtdIns(3,4,5)P3 were detected in beta-cells under non-stimulatory conditions. Insulin secretagogues (28 mM glucose + 0.5 mM carbachol) caused a rapid and transient increase in PtdIns(3,4,5)P3 levels which peaked at 2-5 min, corresponding to peak early phase insulin release. PMID- 7887930 TI - 3"-Azido-3'-deoxythymidine and 2',3'-dideoxycytidine do not inhibit gene-specific DNA repair in hamster cells. AB - 3"-Azido-3'-deoxythymidine (AZT) was the first approved drug for the treatment of the AIDS; however, despite its usefulness, AZT often produces side effects that require cessation of therapy. 2',3'-Dideoxycytidine (ddC) is a related anti retroviral agent in advanced stages of clinical testing. A previous report demonstrated that AZT decreased the repair of UV-induced DNA strand breaks in mammalian cells after ultraviolet (UV) irradiation. We studied the effect of AZT and ddC on DNA repair from the hamster DHFR gene of the major UV-induced DNA lesion, cyclobutane pyrimidine dimers (CPDs). We conclude that neither AZT nor ddC inhibited DNA replication or the gene-specific repair of CPDs in the hamster DHFR gene after 8 or 24 hrs of repair incubation at concentrations of 25 microM and 10 microM, respectively. PMID- 7887931 TI - Solubilization, purification and characterization of fatty acyl-CoA reductase from duck uropygial gland. AB - Membrane-bound fatty acyl-CoA reductase from the uropygial gland of duck has been solubilized from the microsomal preparation with 20% glycerol and 3 M NaCl and purified to homogeneity by Blue A agarose and Palmitoyl-CoA agarose affinity column chromatography followed by Suprose-6 gel filtration. The molecular mass of the enzyme was estimated by SDS-PAGE to be 56 kDa. The enzyme was stable in the presence of 20% glycerol and 1M NaCl and required NADPH for activity. The apparent Kms of the purified enzyme for palmitoyl-CoA and NADPH were 29 microM and 67 microM, respectively. The enzyme activity could be enhanced by the addition of lipid, and the presence of 2 mg/ml BSA enhanced the reductase activity by 5-fold. PMID- 7887932 TI - Effect of dexamethasone on alpha 1-proteinase inhibitor synthesis in human cells of monocytic origin. AB - In this study we provide evidence for downregulation of alpha 1-Proteinase Inhibitor (alpha 1-PI) synthesis in cells of monocytic origin by the glucocorticoid analog, dexamethasone. This factor significantly reduced the basal level of alpha 1-PI expression as well as antagonized the effect of lipopolysaccharide and interleukin-6, stimulators of alpha 1-PI synthesis in cells of monocyte/macrophage lineage. Since increased levels of all of these mediators are observed in both acute infections and inflammatory reactions, their combination may affect the contribution of monocytes to the synthesis of alpha 1 PI. PMID- 7887933 TI - The human chemoattractant complement C5a receptor inhibits cyclic AMP accumulation through Gi and Gz proteins. AB - The human C5a receptor is known to signal through Gi proteins. The ability of the cloned C5a receptor to inhibit adenylyl cyclase or to stimulate phospholipase C through Gi proteins was examined in transfected cells. Activation of recombinant C5a receptors resulted in the stimulation of phospholipase C in Ltk- cells and inhibition of adenylyl cyclase in 293 cells. Pertussis toxin potently abolished both responses indicating the involvement of Gi proteins. Previous studies have shown that Gi-mediated inhibition of adenylyl cyclase can be similarly regulated by the pertussis toxin-insensitive GZ. In 293 cells co-transfected with the alpha subunit of GZ, the C5a-mediated inhibition of cAMP accumulation became pertussis toxin-resistant, signifying functional coupling between the C5a receptor and GZ. However, GZ cannot substitute for Gi in the C5a-induced stimulation of phospholipase C or inhibition of adenylyl cyclase in Ltk- cells. PMID- 7887934 TI - A truncated isoform of human CCK-B/gastrin receptor generated by alternative usage of a novel exon. AB - An isoform cDNA of CCK-B/gastrin receptor was isolated from human stomach. This cDNA differed from initially cloned cDNA only in the 5'-end region and encoded a truncated isoform (delta CCK-B) in which the putative N-terminal extracellular domain of the CCK-B/gastrin receptor was completely lost. Isolation of genomic CCK-B/gastrin receptor DNA revealed that this transcript is generated by alternative usage of a novel exon, termed exon 1b. Human stomach expressed both transcripts of delta CCK-B and entire CCK-B/gastrin receptor (CCK-BR), whereas human stomach cancer cell line AGS exclusively expressed delta CCK-B transcripts. Transfection of COS-7 with delta CCK-B cDNA led to the appearance of binding sites for 125I-CCK-8. Its ligand selectivity was different from that of CCK-BR. These results suggest the molecular diversity in CCK-B/gastrin receptor subtypes. PMID- 7887935 TI - Induction of apoptosis by enediyne antitumor antibiotic C1027 in HL-60 human promyelocytic leukemia cells. AB - C1027, a new macromolecular antitumor antibiotic with an enediyne chromophore, displays extremely potent cytotoxicity against cancer cells. HL-60 human promyelocytic leukemia cells treated with C1027 (0.1-10 nM) for 2 hours resulted in morphological changes, including Hoechst 33342-stained condensed nuclei, condensation of nuclear chromatin, and nuclear fragmentation. Agarose gel electrophoresis of C1027-treated HL-60 cells showed a typical ladder-like pattern of DNA fragments. In addition, the apoptotic DNA peak of propidium iodide-stained nuclei was revealed by flow cytometry. Treatment of HL-60 cells with C1027 (5 nM) induced apoptosis in up to 79% of the cells. The results suggest that C1027 may exert antitumor activity by triggering apoptosis. PMID- 7887936 TI - Cell-cycle-dependent modulation of EGF-receptor-mediated signaling. AB - In A431 cells synchronized by treatment with thymidine, the level of EGF stimulated tyrosine protein kinase activity in cells in S and G2/M phases was reduced approximately 40% relative to that seen in cells in G1. This decrease in receptor tyrosine protein kinase activity did not correlate with a decrease in cell surface EGF receptor expression, indicating that the reduced activity could not be attributed to receptor loss. EGF-stimulated PI 3-kinase activity was also reduced by approximately 60% during S phase as compared to G1 phase. The change was not due to decreased PI 3-kinase expression since Western blot analyses indicated that cellular p85 levels remained constant throughout the cell cycle. These data suggest that the ability of EGF to stimulate biological responses varies during the cell cycle and implicate cell-cycle-dependent processes in the regulation of EGF-receptor-mediated signaling. PMID- 7887937 TI - Long-lived macropinocytosis takes place in electropermeabilized mammalian cells. AB - Electropermeabilization is a technique which allows free access of molecules to cytosol. In the present study, we report on results dealing with the penetration of macromolecules. Under electric conditions that allow maintenance of cell viability at a high level, i.e., at low electric field intensity but long time duration (ms time range), all the pulsed cells become permeable to macromolecules. By loading beta-galactosidase the electro-transferred activity in the cells is maintained over 24 hours. Transfer mediated during the pulse occurs by free diffusion into the cytoplasm, while post pulse transfer takes place by a different pathway. When added a few minutes after application of the electric field, the enzyme enters the cell via a macropinocytosis-like process. This is a new long-term effect of the electric field pulse on the membrane. PMID- 7887938 TI - Functional activity of a biotinylated human neurokinin 1 receptor fusion expressed in the Semliki Forest virus system. AB - The 1.3 S biotinylatable subunit of Proprionibacterium shermanii transcarboxylase complex was fused to the C-terminus of the human neurokinin 1 receptor gene and introduced into the Semliki Forest virus expression vector pSFV1. RNA transcribed from pSFV1-NK1-biot and pSFV-Helper2 was coelectroporated into BHK cells permitting in vivo packaging of recombinant virus. Infection of BHK and CHO cells with SFV-NK1-biot virus yielded high level of the fusion receptor as detected by metabolic labeling, immunoblotting with streptavidin alkaline phosphatase and binding to substance P. Like native receptor, the biotinylated receptor fusion was able to stimulate Ca2+ mobilization in infected CHO cells, indicating functional coupling to guanine-nucleotide-binding proteins. PMID- 7887939 TI - Antiviral activity and metabolism of the castanospermine derivative MDL 28,574, in cells infected with herpes simplex virus type 2. AB - The 6-O-butanoyl derivative of castanospermine (MDL 28,574: BUCAST), an inhibitor of glycoprotein processing, blocked the growth of herpes simplex virus type-2 with the effect markedly enhanced by exposure of cells to the compound pre- as well as post-infection. The effectiveness of the derivative corresponded to an increased uptake with greatest accumulation after virus infection. Gas chromatography/mass spectrometry identified the predominant component in MDL 28,574 treated cells as castanospermine, an inhibitor of alpha-glucosidase 1. The effects of this compound on the synthesis of viral glycoprotein, gB, was determined with the increased molecular weight of the mannose-rich precursor evidence for the modulation of glycoprotein processing. PMID- 7887941 TI - Pituitary adenylate cyclase activating polypeptide is a potent calmodulin inhibitor. AB - We report here that pituitary adenylate cyclase activating polypeptide (PACAP38), a new 38-residue neuropeptide of the secretin/glucagon family, is a potent inhibitor of calmodulin in vitro in the activation of bovine brain calmodulin dependent cyclic nucleotide phosphodiesterase. The concentration of PACAP38 for half-maximal inhibition of the phosphodiesterase is 15 nM, one of the lowest for known calmodulin inhibitors. In the presence of Ca2+, PACAP38 binds strongly to calmodulin in a 1:1 ratio with a dissociation constant of about 28 nM. The binding is not dissociated by 4 M urea. In the absence of Ca2+ the binding is at random and can be dissociated by 4 M urea. Studies with PACAP38 derivatives show that the carboxyl half of the PACAP38 molecule is essential for the inhibition of calmodulin. PMID- 7887940 TI - A metal-dependent form of protein phosphatase 2A. AB - Highly purified bovine heart protein phosphatase 2A catalytic subunit lost virtually all of its activity during storage at -70 degrees. When the enzyme was preincubated with Co2+, over 35% of the original activity was restored. Freshly prepared protein phosphatase 2A purified from bovine heart was stimulated at least 3 to 4-fold by pretreatment with Co2+ or Mn2+. Activation by Co2+ appeared to be irreversible whereas activation by Mn2+ was partially reversed after the cation was chelated with excess EDTA/EGTA. The sensitivity of Co2(+)-stimulated protein phosphatase 2A to okadaic acid or inhibitor-2 was similar to that of spontaneously active protein phosphatase 2A. The enzyme was converted to a latent form by treatment with phosphate or pyrophosphate. The latent form was completely reactivated by preincubation with Co2+. These results demonstrate that protein phosphatase 2A, like phosphatase 1, can exist in a metal ion-dependent form and may represent a new mechanism for the regulation of protein phosphatase 2A activity. PMID- 7887942 TI - Isolation and characterization of an in vitro DNA replication system from maize mitochondria. AB - An in vitro DNA replication system from maize mitochondria has been isolated and characterized. Maize mtDNA polymerase activity was purified about 1100-fold through DEAE cellulose and Heparin-Sepharose columns. In addition to the DNA polymerase activity, this in vitro replication system also contained topoisomerase I, DNA primase and RNA polymerase activities. Optimal conditions for enzyme activity, preferred templates and inhibitors were determined in order to further characterize this in vitro replication system; this system was devoid of any detectable extramitochondrial activity as determined by: a) the mt origin of the DNA polymerase activity as evidenced by studies using different templates and inhibitors, b) absence of chloroplast or nuclear DNA, glucose -6-P dehydrogenase (known to be present only in the cytosol and chloroplasts) and photosynthetic pigments in the mitochondrial fraction and c) the ability of maize mt topoisomerase I to relax positively supercoiled DNA. PMID- 7887943 TI - Functional couplings of the delta- and the kappa-opioid receptors with the G protein-activated K+ channel. AB - The delta- and the kappa-opioid receptors were individually co-expressed with the G-protein-activated K+ (GIRK1) channel in Xenopus oocytes. Stimulation of these opioid receptors with selective agonists induced currents which were blocked by the opioid receptor antagonist naloxone. The current responses showed inward rectification and were blocked by 300 microM Ba2+, indicating that the effect of activated opioid receptors was mainly mediated by the GIRK1 channel. The EC50 value obtained from these responses was 45 nM for the agonist DPDPE in the oocytes injected with the delta-opioid receptor mRNA and the GIRK1 mRNA and 15 nM for the agonist U50488H in the oocytes injected with the kappa-opioid receptor mRNA and the GIRK1 mRNA. The Hill coefficient was 0.92 in the former and 0.93 in the latter. These results suggest that each of the delta- and the kappa-opioid receptors functionally couples with the GIRK1 channel. PMID- 7887944 TI - A human (3.3 kb) haptoglobin-CAT transgene is modulated in lungs of transgenic mice by inflammation. AB - Four independent lines of transgenic mice were produced carrying integrated copies of a chimeric gene composed of 3.3 kb of the human haptoglobin 5' regulatory region fused to the CAT (chloramphenicol acetyl transferase) reporter gene. Although the endogenous mouse haptoglobin (Hp) and human haptoglobin (HP) genes express mainly in liver and lung, expression of the human 3.3-kb HP-CAT transgene was not detected until after induction of inflammation and then only in lungs. The results indicated that the transgene maintained the regulatory DNA elements required for lung specific responsiveness to inflammation in vivo but lacked the DNA sequence required for robust expression in liver. The DNA sequence(s) responsible for the normally high level of HP expression in liver either reside outside the 3.3-kb regulatory region of the HP chimeric gene or this region contains a suppressor sequence affecting tissue specific expression in the liver. PMID- 7887945 TI - Experimental studies on bone inducing activity of composites of atelopeptide type I collagen as a carrier for ectopic osteoinduction by rhBMP-2. AB - Atelopeptide type I collagen derived from fresh porcine skin was evaluated as a carrier for ectopic osteoinduction by recombinant human bone morphogenetic protein-2 (rhBMP-2) in rats. Four treatment groups (N = 5) were examined: a control group in which only atelopeptide type I collagen was implanted, and groups II, III and IV in which atelopeptide type I collagen with 2, 10, 50 micrograms of rhBMP-2 was implanted in to the calf muscles of 10-week-old Wistar rats, respectively. Four weeks after the implantation, soft X-ray and light microscopic examinations were performed. In addition, calcium (Ca) content and alkaline phosphatase (ALP) activity were evaluated. New bone formation in the implanted regions (groups II, III and IV) were revealed. Bone formation was induced in the implanted region of even 2 micrograms of rhBMP-2 (group II), and its degree was dependent on the dose of rhBMP 2. These results indicate that atelopeptide type I collagen is an effective carrier for ectopic osteo-induction by rhBMP-2 and may act as a carrier for rhBMP in reconstructive surgery for bony defect and augmentation. PMID- 7887946 TI - Adenylyl cyclase isoforms are differentially expressed in primary cultures of endothelial cells and whole tissue homogenates from various rat tissues. AB - The expression of five adenylyl cyclase isoforms (types II-VI) was studied with reverse transcription-polymerase chain reaction in whole tissue homogenates and in primary cultures of endothelial cells isolated from rat aorta, vena cava, heart, lung, adipose fat, brain, and adrenal medulla. It was found that: i) all endothelial cell types express all adenylyl cyclase isoforms studied, albeit at different levels depending on the tissue origin of the cells, and ii) the adenylyl cyclase isoform profile of isolated endothelial cells differs from that of homogenates of their parent tissues. Our data show a unique endothelial cell type specificity of AC isoform expression, which varies from that of the whole organ. These results support the idea that one of the factors mediating differential regulation of the cAMP cascade in EC in various locations within the vascular tree might be quantitative differences in the levels of AC isoforms expressed in each EC type. PMID- 7887947 TI - A model for the sequence-dependent DNA binding of 4',6-diamidino-2-phenylindole (DAPI). AB - A study on the sequence dependent DNA binding mode of DAPI has been carried out on pUC8 and the beta gal promoter region by restriction endonuclease and DNAase I protection experiments. A molecular model depicting drug interaction at the level of selected palyndromes has also been constructed that confirms the A-T sequence specificity of the compound. Experimental data indicate that the binding sites for RNA polymerase and cyclic AMP receptor protein (CRP) in the beta gal gene are privileged locales for DAPI interaction, a feature that explains impairment of transcription at this level. From a stereochemical view point, DAPI binding to DNA minor groove, while being incompatible with promoter unwinding in the open complex, may also disturb optimal contacts with proteins regulating RNA polymerase activity. PMID- 7887948 TI - Isolation and structural analysis of the 5' flanking region of the gene encoding the human glucagon receptor. AB - The gene encoding the human glucagon receptor, including several kb of upstream sequence, was isolated from a bacteriophage lambda FIX II library constructed from human placental DNA. We report here the novel sequence of the 5' flanking region of the gene, the identification of a previously unreported intron of 5 kb, and the identification of the transcription start point of the glucagon receptor specific transcript, which estimates the length of the first exon to be 300 bp. PMID- 7887949 TI - The leukotriene LTD4 receptor antagonist MK571 specifically modulates MRP associated multidrug resistance. AB - The multidrug resistant cell lines HL60/AR and GLC4/ADR show high overexpression of the gene encoding the multidrug resistance associated protein MRP compared to their drug sensitive parental counterparts. This and the virtual absence of mdr1/P-glycoprotein gene expression was proven by a complementary DNA polymerase chain reaction (cDNA-PCR) approach. Applying a 72-hour tetrazolium based colorimetric MTT-assay we demonstrate on both MDR sublines a dose-dependent modulation of drug resistances by the leukotriene LTD4 receptor antagonist MK571. A complete reversal of vincristine resistances was achieved at final MK571 concentrations of 30 microM (HL60/AR) or 50 microM (GLC4/ADR) which by itself did not disturb cellular proliferation. The drug resistance of a mdr1/P-gp overexpressing multidrug-resistant HL60 subline, in contrast, was not significantly affected by MK571. Similar effects were seen using the glutathione (GSH) synthesis inhibitor buthionine sulfoximine (BSO). Our results point to a relationship between MRP and a conjugate transporter and identify MK571 as a new tool structure for developing modulators specific for a MRP associated multidrug resistance. PMID- 7887950 TI - Activation of the Sendai virus fusion protein by receptor binding. AB - 2,3 Dehydro-2-deoxy-N-acetyl-neuraminic acid (DNANA) competitively inhibits the neuraminidase activity of Hemagglutinin-neuraminidase (HN) from Sendai virus. The inhibition constant depends on the presence of the Fusion (F) protein, which is 30 microM in the presence of active F protein and 50 microM when the F protein is inactivated. These data correlate with previously reported evidence of interaction of the F protein with HN (Dallocchio, F., Tomasi, M., & Bellini, T. (1994) Biochem. Biophys. Res. Comm. 201, 988-993). Desialyzation of erythrocytes, by Clostridium neuraminidase, lowers the hemolytic activity of SV to < 0.1% of that observed on untreated erythrocytes. However, addition of DNANA causes a concentration-dependent increase of hemolytic activity. Both HN and the F protein are required for the activation of hemolytic activity by DNANA. The affinity constant for DNANA, calculated from the activation of hemolytic activity on desialyzed erythrocytes, is 35 microM, very close to the Ki for neuraminidase activity. These data suggest that the binding of the F protein to HN, induced by the binding to HN of a substrate or a substrate analogue, causes a conformational change which activates the F protein. PMID- 7887951 TI - Structure of the gene encoding the alpha subunit of the human interleukin 3 receptor. AB - Interleukin 3 is a cytokine that stimulates proliferation and differentiation of hematopoietic progenitor cells. Its receptor consists of two subunits, an interleukin 3-specific alpha subunit and a beta subunit shared by garanulocyte macrophage colony stimulating factor and interleukin 5 receptors. In this paper, we determined the genomic structure of the alpha subunit of the human interleukin 3 receptor, which spans approximately 40 kb and has 12 exons. We found that the genomic structures of the alpha subunits of the human interleukin 3 and granulocyte-macrophage colony stimulating factor receptors are very similar. They possess a unique additional intron in the 'C domain', which is absent in the alpha subunit of the interleukin 5 receptor. These results suggest a shared evolutionary pathway of these two genes. PMID- 7887952 TI - Calpain dissociates into subunits in the presence of calcium ions. AB - Calpain is a calcium dependent cysteine protease consisting of a catalytic 80K subunit and a regulatory 30K subunit. It has therefore been believed that calpain functions as a dimer. Here we have found that calpain dissociates into subunits in the presence of the Ca2+ required for the expression of activity and that the dissociated 80K subunit is enzymatically fully active. Moreover, the 80K subunit shows a calcium sensitivity identical to the activated form of calpain but not to the original control calpain. The results suggest that the activation of calpain corresponds to the dissociation into subunits in the presence of Ca2+ and that calpain functions as a monomer of the 80K subunit in vivo. PMID- 7887953 TI - Identification of N-acetylglucosamine-alpha-1-phosphate transferase activity in Dictyostelium discoideum: an enzyme that initiates phosphoglycosylation. AB - A lysosomal proteinase from Dictyostelium discoideum was previously shown to have GlcNAc alpha-1-P residues in phosphodiester linkage to serine. We have identified a GlcNAc-alpha-1-P transferase activity in membrane preparations using UDP[3H]GlcNAc and a peptide acceptor with three tandem Ser-Gly repeats. We established an assay, proved the structure of the product, determined the Kms for donor and acceptor and showed that the glycopeptide binds a GlcNAc-alpha-1-P specific rabbit antibody. These findings provide the tools to search for mutants lacking GlcNAc-alpha-1-P transferase activity as a probe for the function of this modification we call phosphoglycosylation. PMID- 7887954 TI - Identification of N-terminus peptide of human granulocyte/macrophage colony stimulating factor as the site of nucleotide interaction. AB - The interaction of nucleotides with recombinant human granulocyte/macrophage colony stimulating factor (rhGM-CSF) has been investigated. Utilizing nucleotide photoaffinity probes [gamma 32P]-8N3ATP and [beta 32P]-8N3Ap4A, an analog of alarmone, the specificity of interaction was demonstrated by saturation of photoinsertion by these analogs and protection of photoinsertion by these analogs in the presence of natural nucleotide. The site of photoinsertion was tentatively determined to be Ser9. The photolabeled cytokine has lost most of its biological activity in a cellular proliferation assay, indicating a possible physiological role for this interaction. PMID- 7887955 TI - Phosphorylation of calponin mediated by protein kinase C in association with contraction in porcine coronary artery. AB - Calponin is an actin-associated regulatory protein in smooth muscle. We report that both endothelin-1 (ET-1) and phorbol 12, 13-dibutyrate (PDBu) caused a significant increase in phosphorylation of calponin during contraction of porcine coronary artery, while high levels of KCl were ineffective. This phosphorylation was predominantly catalyzed by activation of protein kinase C(PKC). In addition, the level of phosphorylation of calponin increased closely in association with the size of the contractile force induced by PDBu. Thus, the phosphorylation of calponin in vivo by PKC might modulate in part the contraction of smooth muscle that occurs in response to ET-1 or PDBu. PMID- 7887956 TI - The molecular mechanism of the induction of the low density lipoprotein receptor by chenodeoxycholic acid in cultured human cells. AB - In a cultured human hepatoblastoma cell line, Hep G2, chenodeoxycholic acid (CDCA) induced LDL receptor mRNA levels approximately 4 fold and mRNA levels for HMG-CoA reductase and HMG-CoA synthase two fold. In contrast, the mRNA levels for mevalonate kinase, farnesyl pyrophosphate synthase and squalene synthase were not changed significantly. The pattern of the induction of the sterol-sensitive genes was similar to the induction by N-acetyl-leucyl-leucyl-norleucinal (ALLN), an SREBP degradation inhibitor, suggesting that CDCA may increase mature SREBPs. CDCA could inhibit the 25-hydroxycholesterol mediated inactivation of SREBP without affecting mRNA levels of SREBPs. These results suggest that CDCA can affect sterol metabolism by a novel mechanism involving the inhibition of the oxysterol-mediated inactivation of SREBP. PMID- 7887957 TI - Androgens and estrogens markedly inhibit expression of a 20-kDa major protein in hamster exorbital lacrimal gland. AB - We report here for the first time a 20-kDa hamster lacrimal gland major protein whose expression is markedly inhibited by physiological levels of both androgens and estrogens. This novel protein was present in adult females but not in males. In females, its level was several fold elevated on ovariectomy to apparently 20% of total soluble proteins. Castration in males induced this 20-kDa protein from undetectable to ovariectomized female levels. Administration of only androgens or estrogens to gonadectomized hamsters of both sexes obliterated this major lacrimal protein and estrogens were more potent than androgens. The 20-kDa lacrimal protein was secreted only in female tears. This lacrimal 20-kDa protein of yet unknown function is a useful marker to study the hormonal regulation of the lacrimal gland and it provides a model system to study how both androgens and estrogens mediate inhibition of a specific protein's expression. PMID- 7887958 TI - Halogenated benzimidazoles and benzotriazoles as selective inhibitors of protein kinases CK I and CK II from Saccharomyces cerevisiae and other sources. AB - Several halogeno benzimidazole riboside inhibitors of animal and plant protein kinases CK I and CK II (also known as casein kinases I and II), were found to be effective inhibitors of Saccharomyces cerevisiae CK II, but not of the 27-kDa CK.I or the 45-kDa CK I. The previously reported 5,6-dichloro-2-azabenzimidazole, which preferentially inhibits plant CK II relative to CK I, discriminates even more effectively between the yeast CK I and CK II enzymes. Two new analogues, tetrahalogeno-2-azabenzimidazoles, are even more potent inhibitors of CK II and much less so of CK I from yeast and animal sources. All inhibitors are competitive with respect to ATP (and GTP with CK II), the two latter with Ki values in the range 0.2-0.6 microM for CK II from yeast and mammalian sources. PMID- 7887959 TI - Retention of the label during the conversion of [3-3H] squalene into (3S)-2,3 oxidosqualene catalyzed by mammalian squalene oxidase. AB - Squalene epoxidase is the only known flavoprotein that catalyzes the epoxidation of an olefin. In order to test the possibility of a catalytic non-heme metal based mechanism, the conversion of chemically synthesized [3-3H]squalene into [3H]2,3-oxidosqualene, by partially purified pig liver squalene epoxidase, was studied. No exchange of the labeled hydrogen could be observed, ruling out a mechanism involving, e.g., an iron carbene type species at C-3. PMID- 7887960 TI - Quercetin down-regulates signal transduction in human breast carcinoma cells. AB - Signal transduction activity was markedly elevated in cancer cells as shown by the increased activity of enzymes utilizing 1-phosphatidylinositol, PI (PI 4 kinase and PI-4-phosphate 5-kinase) for the production of the second messenger inositol 1,4,5-trisphosphate, IP3, in rat hepatomas (Cancer Res. 54: 2611;5574, 1994) and in human ovarian and breast carcinoma cells (Life Sci. 55:1487, 1994). Quercetin, a flavonoid, in human breast carcinoma MDA-MB-435 cells produced growth inhibition (IC50 = 55 microM) and cytotoxicity (LC50 = 26 microM). Quercetin inhibited PI kinase activity in extracts of breast carcinoma cells (IC50 = 6 microM) and in cultured cells (IC50 = 10 microM) with a minor inhibition of PIP kinase activity. IP3 concentration decreased in parallel with PI kinase activity. In time sequence studies quercetin in breast carcinoma cells brought down PI kinase and IP3 concentration in 60 min to 5 and 6%, respectively; PIP kinase activity was at 63% of controls. The results demonstrate for the first time in proliferating human breast carcinoma cells a reduction by quercetin of the increased capacity for signal transduction, thus providing a novel and sensitive target in cancer cells. PMID- 7887961 TI - Hypoxia-induced transcription of the vascular endothelial growth factor gene is independent of functional AP-1 transcription factor. AB - In this study, we investigated the functional role of the transcription factor AP 1 in hypoxia-induced expression of the vascular endothelial growth factor (VEGF) by using dexamethasone as an inhibitor of AP-1 activity. Phorbol ester and platelet-derived growth factor (PDGF) cause an increase in VEGF mRNA expression, which is strongly suppressed in the presence of dexamethasone, whereas hypoxia induced VEGF expression is not inhibited by dexamethasone. Studies using a VEGF promoter luciferase construct show that the phorbol ester and PDGF-induced VEGF expression is mediated at least in part by transcriptional activation of the VEGF promoter, whereas no transcriptional activation is seen under hypoxic conditions. In contrast, hypoxia leads to an increase in VEGF mRNA stability, as confirmed by experiments using actinomycin D as an inhibitor of transcription. These results indicate that hypoxia-induced VEGF expression is independent of AP-1 mediated transcription. PMID- 7887962 TI - Sensitization of InsP3-dependent calcium signalling through structural modification of voltage-dependent calcium channel: a physiological relevance of the calcium channel beta subunit. AB - The expression in Xenopus oocytes of the human voltage-dependent Ca2+ channel (VDCC) beta 2 subunit subtype (h beta 2) enhances the endogenous Ca2+ channel activity. By using the native Ca(2+)-dependent chloride conductance to monitor fast intracellular Ca2+ variations, we point out that the beta-enhanced Ca2+ entry (T1 component) is currently associated with a second delayed elevation of internal Ca2+ (T2 component). Further experiments show that this additional component absolutely requires Ca2+ entry through the beta-modulated channels although it directly derives from a Ca2+ release from intracellular inositol (1,4,5)-trisphosphate (InsP3)-sensitive stores. Finally, our study demonstrates that InsP3-evoked response in oocytes is dramatically modified since it gains a new shape of voltage dependency directly derived from the beta-modified Ca2+ influx. The main conclusion is that the spatiotemporal pattern of InsP3-dependent Ca2+ release may be closely influenced by the intrinsic characteristics of working VDCCs. PMID- 7887963 TI - Parathyroid hormone-related peptide as a locally produced vasorelaxant: regulation of its mRNA by hypertension in rats. AB - The present study was undertaken to examine the effect of parathyroid hormone related peptide (PTHrP) on the vascular tone as well as the expression of its mRNA in the cardiovascular system and its regulation in response to systemic hypertension in Sprague-Dawley rats. In aortic rings precontracted with 0.3 microM norepinephrine PTHrP(1-34) caused a dose-dependent relaxation with the maximal response of 33% being observed at 10(-6) M. PTHrP was nearly equipotent to PTH or CGRP in the vasodilatory action. Ribonuclease protection assay and Northern blot analysis demonstrated that PTHrP mRNA levels in the heart and aorta were increased as a result of systemic hypertension induced by constant infusion of angiotensin II and salt loading. The results of our in vivo studies suggest an autocrine/paracrine role for PTHrP as a local regulator of the vascular tone. PMID- 7887964 TI - Evidence for a functional interaction between calmodulin and the glucocorticoid receptor. AB - In the signaling cascade of membrane-bound receptors, calmodulin (CaM) plays an important role. However, little is known about the role of CaM in the activation of intracellular steroid receptors, which are known to act as ligand-regulated transcription factors. We report here that CaM can interact in a calcium dependent manner with the untransformed glucocorticoid receptor (GR) complex containing hsp90. In addition, we demonstrate that four unrelated CaM antagonists (trifluoperazine, compound 48/80, W7, and phenoxybenzamine) can inhibit GR mediated gene expression in mouse L929 cells stably-transfected with the MMTV-CAT reporter gene. These results provide evidence that CaM may play an important role in the signal transduction pathways of steroid hormone receptors. PMID- 7887965 TI - In the thermophilic archaeon Sulfolobus solfataricus a DNA-binding protein is in vitro (Adpribosyl)ated. AB - A small protein with high affinity for homologous DNA was isolated from Sulfolobus solfataricus homogenate by mineral acid extraction. It was purified using a two-step procedure including CM-cellulose and RP-HPL chromatographies. The protein was electrophoretically homogeneous, had a molecular weight of 7.147 kDa and an amino acid composition with a high content of lysine and glutamic acid residues. The protein was able to protect DNA against thermal denaturation and DNAse I digestion in a dose-dependent manner. After incubation of the sulfolobal homogenate in the presence of 32P-NAD, followed by the purification steps, the protein was modified by ADPribose, as revealed by reaction product analysis, SDS PAGE and autoradiography. PMID- 7887966 TI - Ethanol enhances the stimulatory effects of insulin and insulin-like growth factor-1 on DNA synthesis in NIH 3T3 fibroblasts. AB - In practically all in vitro experimental systems examined so far, including embryonal fibroblasts, ethanol was shown to inhibit cell growth. Here we report that in NIH 3T3 fibroblasts, (patho)physiologically relevant concentrations (50 100 mM) of ethanol significantly (2- to 2.8-fold) enhanced the stimulatory effects of both insulin and insulin-like growth factor-1 on DNA synthesis. Ethanol had no major effects on the mitogenic effects of platelet-derived growth factor, fibroblast growth factor and lyso-phosphatidic acid. These data suggest that ethanol is not a universal inhibitor of cell growth. PMID- 7887967 TI - CD 69 antigen of human lymphocytes is a calcium-dependent carbohydrate-binding protein. AB - CD69 is a signal transducing molecule of hematopoietic cells. Previous molecular cloning of CD69 has revealed a type II transmembrane orientation and the presence of an extracellular domain related to the Ca(2+)-dependent (C-type) animal lectins. As the predicted amino acid sequence for the lectin-like domain is highly divergent from those of other C-type lectin-like proteins - a feature shared with NKR-P1 of natural killer cells - CD69 and NKR-P1 are among proteins assigned to a separate group, group V. To initiate ligand identification studies, we have prepared soluble forms of CD69 protein by bacterial expression of its extracellular portion. We show that cysteine 68 located in the short membrane proximal neck region of CD69 which adjoins the C-terminal lectin-like domain is a critical element for dimerization. We have evidence that the soluble dimeric CD69 has a tight association with calcium, a feature shared with NKR-P1, and that it is a carbohydrate-binding protein with N-acetyl-D-glucosamine and N-acetyl-D galactosamine as the best inhibitors: 4-8 x 10(-5) M giving 50% inhibition of binding to N-acetyl-D-glucosamine neoglycoprotein. Thus, the tight association with calcium and high affinities for carbohydrate binding appear to be features of at least two members of the C-type lectin group V. PMID- 7887968 TI - Differential effects of a hydrophobic tripeptide on human immunodeficiency virus type 1 (HIV-1)-induced syncytium formation and viral infectivity. AB - The synthetic hydrophobic peptide, Z-D-Phe-L-Phe-Gly, was shown previously to inhibit the infectivity of paramyxoviruses and the fusion of Sendai virus with liposomes. We examined the ability of this peptide to inhibit HIV-1 infectivity in A3.01, Sup-T1, and H9 cells and syncytium formation between these cells and chronically infected H9 cells. Although the peptide inhibited syncytium formation in a dose-dependent manner, its effect on virus infectivity was very limited. Our results suggest that the mechanisms of interaction of the HIV-1 envelope glycoprotein gp120/gp41 with the target cell membrane leading to membrane fusion may be different in cell-cell and virus-cell fusion. PMID- 7887969 TI - Autocrine production of endothelin-1 participates in the glucocorticoid-induced Ca2+ influx into vascular smooth muscle cells. AB - We determined whether endothelin-1 (ET-1) is associated with glucocorticoid induced Ca2+ influx into vascular smooth muscle cells by examining the effects of the ETA receptor antagonist FR139317 on dexamethasone-induced 45Ca2+ uptake and dihydropyridine binding by rat A7r5 cells. FR139317 inhibited the dexamethasone induced 45Ca2+ uptake and [methyl-3H]PN 200-110 binding in a dose-dependent manner. Slot blot analysis revealed that dexamethasone increased protein kinase C alpha in A7r5 cells and that this effect was also abolished by FR139317. Dexamethasone stimulated the release of immunoreactive endothelin-1 from A7r5 cells into the culture medium. These results suggest that endothelin participates in the glucocorticoid-induced Ca2+ influx through dihydropyridine-sensitive channels in an autocrine manner, possibly linked to the activation of protein kinase C-alpha. PMID- 7887970 TI - Molecular cloning of the human volume-sensitive chloride conductance regulatory protein, pICln, from ocular ciliary epithelium. AB - Chloride channels in the ocular ciliary epithelium are believed to play a key role in aqueous humor formation. We isolated a cDNA clone from a lambda Uni-ZAP cDNA library of human nonpigmented ciliary epithelial (NPE) cells encoding the swelling-induced chloride channel/channel regulator pICln. The human clone contains an open reading frame of 237 amino acids (M(r) 26,293). The deduced human amino-acid sequence shows 90.2% and 92.7% identity with counterparts isolated from rat kidney and the canine kidney epithelial cell line MDCK. Human NPE cell lines exhibited significant levels of pICln transcripts. Complementary perforated-patch, whole-cell patch clamping demonstrated that swelling activates Cl- channels of the NPE cells, as suggested by ruptured-patch measurements. The results document the molecular isolation and identification of a human cDNA clone of a Cl- conductance regulator from ocular cells displaying volume-activated Cl channels. PMID- 7887971 TI - Role of Thr-252 in cytochrome P450cam: a study with unnatural amino acid mutagenesis. AB - Replacement of Thr-252 in the active center of cytochrome P450cam with a non hydroxy amino acid residue such as Ala and Val by conventional site-directed mutagenesis converted this monooxygenase to an NADH oxidase (Imai, M. et al. Proc. Natl. Sci. U. S. A. 86, 7823-7827, 1989). In this study, a mutant enzyme with a methoxy group in place of the hydroxy group of Thr-252 (OMe-mutant) was synthesized by the method of unnatural amino acid mutagenesis (Noren, C. J. et al., Science 244, 182-188, 1989). Unlike other site-directed mutants without a hydroxy group at the position, the OMe-mutant retained a considerably high monooxygenase activity, yielding a stoichiometric amount of 5-exo-hydroxycamphor to that of the oxygen consumed. Thus a free hydroxy group at this position is not an indispensable requisite for the monooxygenase to cleave the O-O bond of molecular O2 as previously proposed. PMID- 7887972 TI - Bile acids as endogenous vasodilators? PMID- 7887973 TI - Particular ability of cytochromes P450 3A to form inhibitory P450-iron-metabolite complexes upon metabolic oxidation of aminodrugs. AB - The ability of 21 drugs containing an amine function to form inhibitory P450-iron metabolite complexes absorbing around 455 nm was studied on liver microsomes from rats treated with various P450 inducers. These drugs belong to different chemical and therapeutic series and exhibit very different structures. In the case of eight compounds (diltiazem, lidocaine, imipramine, SKF 525A, fluoxetine, L-alpha acetylmethadol, methadol and desmethyltamoxifen) whose oxidation by microsomes from rats treated with several inducers was studied, only dexamethasone (DEX) treated rat microsomes and, to a lesser extent, phenobarbital (PB)-treated rat microsomes, were able to give significant amounts of 455 nm absorbing complexes. Ten of the 21 compounds studied gave such complexes with DEX-treated rat microsomes, while only three compounds gave complexes (in low amounts) with PB treated rat microsomes only. For all compounds leading to complexes both with DEX and PB-treated rat microsomes, much higher amounts of complexes were obtained with DEX-treated rat microsomes. DEX-treated rat microsomes also led to the most intense type I spectral interactions with most of the compounds studied, and very often exhibited the highest N-dealkylation activities towards the tertiary or secondary amine function of the drugs used. A few exceptions aside, there generally exists a qualitative relationship between the ability of P450 3As, induced by DEX, to bind and N-dealkylate amino compounds and their propensity to lead to 455 nm absorbing complexes. This was confirmed by in vivo experiments showing that rats treated with diltiazem, tamoxifen or imipramine accumulated large amounts of 455 nm absorbing complexes in their liver only after pretreatment with DEX and, to a lesser extent, with PB. This particular ability of P450 3As to oxidize amino drugs with formation of inhibitory P450-metabolite complexes could be of great importance for the appearance of drug interactions in man. PMID- 7887974 TI - Mechanism of action of dexniguldipine-HCl (B8509-035), a new potent modulator of multidrug resistance. AB - It has previously been shown that dexniguldipine-HCl (B8509-035) is a potent chemosensitizer in multidrug resistant cells [Hofmann et al., J Cancer Res Clin Oncol 118: 361-366, 1992]. It is shown here that dexniguldipine-HCl causes a dose dependent reduction of the labeling of the P-glycoprotein by azidopine, indicating a competition of dexniguldipine-HCl with the photoaffinity label for the multidrug resistance gene 1 (MDR-1) product. Exposure to dexniguldipine-HCl results in a dose-dependent accumulation of rhodamine 123 in MDR-1 overexpressing cells. In the presence of 1 microM dexniguldipine-HCl, rhodamine 123 accumulated in multidrug resistant cells to similar levels as in the sensitive parental cell lines. At this concentration, dexniguldipine-HCl enhances the cytotoxicities of Adriamycin and vincristine. The resistance modulating factors (RMF), i.e. IC50 drug/IC50 drug + modulator, were found to be proportional to the expression of MDR-1, ranging from 8 to 42 for Adriamycin and from 16 to 63 for vincristine. Transfection with the MDR-1 gene was found to be sufficient to sensitize cells to the modulation by dexniguldipine-HCl. The compound does not affect the expression of the MDR-1 gene. Dexniguldipine-HCl has no effect on a multidrug resistant phenotype caused by a mutation of topoisomerase II. It is concluded that dexniguldipine-HCl modulates multidrug resistance by direct interaction with the P-glycoprotein. PMID- 7887975 TI - Transcriptional and post-transcriptional analysis of peroxisomal protein encoding genes from rat treated with an hypolipemic agent, ciprofibrate. Effect of an intermittent treatment and influence of obesity. AB - The treatment of rats with ciprofibrate, a potent peroxisome proliferator, led to increased levels of the peroxisomal acyl-CoA oxidase (ACO) mRNA. How ciprofibrate functions to elevate ACO mRNA is not known. To help determine the mechanism of ciprofibrate action, in vitro transcription assays were performed. It was determined that ciprofibrate was responsible for a 3.5-fold stimulation of the rate of ACO transcription within 24 hr of ingestion. It was also observed that the transcription rate stimulation following a 2-week ciprofibrate treatment of Wistar rats was maintained following 4 weeks of ciprofibrate withdrawal. Re introduction of the drug after the 4-week pause resulted in greater stimulation than was initially observed. The results demonstrate that the effect of ciprofibrate is rapid and persists at least twice as long as the initial treatment period. In Zucker rats, both lean and obese, ACO mRNA levels were examined following 2 weeks of ciprofibrate treatment (1 or 3 mg/kg body weight/day). The presence of increased blood levels of triglycerides did not increase ciprofibrate action on transcription, although basal levels of transcription of peroxisomal enzymes were higher in obese rats. The increase in the ACO mRNA level was greater than the transcription rate stimulation suggesting a post-transcriptional regulation. PMID- 7887976 TI - Stimulation of epidermal proliferation in mice with 1 alpha, 25-dihydroxyvitamin D3 and receptor-active 20-EPI analogues of 1 alpha, 25-dihydroxyvitamin D3. AB - The effects of 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3) and receptor active 20-epi vitamin D analogues (MC 1288, 20-epi-1 alpha, 25-(OH)2D3; MC 1301, 20-epi-24a-homo-26,27-dimethyl-1 alpha, 25-(OH)2D3, and KH 1060: 20-epi-22-oxa 24a-homo-26,27-dimethyl-1 alpha, 25-(OH)2D3) on epidermal proliferation in mice were studied in vivo. Single topical applications of all compounds induced epidermal proliferation in a dose-dependent manner. The relative potencies in vivo (KH 1060 > MC1301 > MC1288 > 1 alpha, 25-(OH)2D3) correlated well with the known activities of these compounds to inhibit U 937 cell proliferation in vitro. Vitamin D3 and 1 beta, 25-(OH)2D3, two compounds that do not bind the vitamin D receptor, did not affect epidermal proliferation. Our study shows that vitamin D3 compounds that bind to the vitamin D receptor stimulate epidermal proliferation in mice. PMID- 7887977 TI - 11B nuclear magnetic resonance studies of the interaction of borocaptate sodium with serum albumin. AB - The interaction between borocaptate sodium, Na2B12H11SH (BSH), and three types of serum albumin--bovine, human and dog (BSA, HSA and DSA)--has been investigated quantitatively using 11B NMR. The 11B chemical shifts and relaxation rates of BSH were studied with various concentrations of serum albumin (1-5%, w/v) at 295-310 degrees K. Correction of the longitudinal relaxation rate (R1) due to protein viscosity effects was accomplished. The corrected R1 values were analyzed mathematically using a saturation function and linear regression. The linewidths of 11B resonances, which are related to the spin-spin relaxation rates (R2), were also measured. The binding fractions (P), the number of binding sites (NBS), and the binding constants (Kb) of BSH at various concentrations of the three types of serum albumin (1-5%, w/v) were determined at 295 and 310 degrees K. We speculate that the nature of this interaction may be electrostatic. PMID- 7887978 TI - Autoradiographic evaluation of the influence of hypothalamic 5,7 dihydroxytryptamine lesion on brain serotonin synthesis. AB - The influence of a unilateral stereotaxically induced 5,7-dihydroxytryptamine (5,7-DHT) lesion in the dorsolateral hypothalamus on brain serotonin synthesis was evaluated by an autoradiographic method, using labelled alpha-methyl-L tryptophan (alpha-MTrp). The hypothalamus was selected as the lesion site because it receives well defined and relatively large projections from the raphe nuclei. Data suggest that the unilateral lesion in the dorsolateral hypothalamus had a significant influence (an increase) on the rate of serotonin synthesis in the large majority of ipsilateral brain structures examined. It seems that the effect was the greatest in the hippocampal structures, the thalamus, and the parietal and sensory motor cortices. The average increase in the rate of serotonin synthesis on the lesion side when compared with the contralateral side was between 3% (amygdala) and 52% (dorsal hippocampus; CA3 layer of hippocampus). Since in the sham-injected rats (same volume of saline) there was no obvious injection-contralateral side asymmetry observed (except for two structures, probably affected by the injection needle, which showed a significant difference), we concluded that the effect observed in the present study was most likely related to the 5,7-DHT-induced lesion on the serotonergic terminals in the hypothalamus. Comparison of the rate of synthesis in the dorsal and medial raphe and the pineal body with the rates reported earlier for these structures led us to conclude that either the 5,7-DHT lesion in the hypothalamus did not influence the rates in these structures in their entirety, or the method used was not sensitive enough to reveal this influence. Data reported here also demonstrate how a highly specific tracer (alpha-MTrp), in conjunction with a specific and localized lesion, could aid our understanding of the brain serotonergic system. PMID- 7887979 TI - N-[2-[N'-pentyl-(6,6-dimethyl-2,4-heptadiynyl)amino]ethyl]- (2-methyl-1 naphthylthio)acetamide (FY-087). A new acyl coenzyme a:cholesterol acyltransferase (ACAT) inhibitor of diet-induced atherosclerosis formation in mice. AB - FY-087 (N-[2-[N'-pentyl-(6,6-dimethyl-2,4-heptadiynyl)amino]ethyl]- (2-methyl-1 naphthylthio)acetamide) was found to be a competitive inhibitor of human microsomal acyl coenzyme A:cholesterol acyltransferase (ACAT) with an IC50 value of 0.11 microM. Under our assay conditions, other ACAT inhibitors tested, specifically YM-750, E-5324, and melinamide, all of which are now in phase I clinical trials or in clinical use in Japan, inhibited this enzyme with IC50 values of 0.18, 0.14, and 3.2 microM, respectively. FY-087 also inhibited ACAT in acetyl-low density lipoprotein loaded human macrophages (THP-1 cells) with an IC50 of 0.17 microM. Following the oral administration of FY-087 (30 mg/kg) to rats, the plasma concentration of FY-087 reached 0.42 microgram/mL after 2 hr. This concentration of FY-087 was enough to inhibit blood vessel ACAT activity. Cholesterol-lowering and anti-atherogenic effects of FY-087 were examined using C57BL/6J mice fed an atherogenic diet. In this mouse model, treatment with FY-087 (28 mg/kg) inhibited the increase in plasma cholesterol levels by about 20% and decreased the hepatic accumulation of free and esterified cholesterol by 61 and 67%, respectively. FY-087 also significantly inhibited the atherogenic diet induced increase in the fatty-streak lesion area of the proximal aorta by 57% in C57BL/6J mice. These results indicate that FY-087 is not only a therapeutically bioavailable ACAT inhibitor that lowers plasma cholesterol levels, but also an effective anti-atherogenic agent in mice fed an atherogenic diet. PMID- 7887980 TI - Expression of fibronectin and interstitial collagen genes in smooth muscle cells: modulation by low molecular weight heparin fragments and serum. AB - The effect of low M(r) heparin fragments (CY222) and fetal calf serum (FCS) on the level of fibronectin and fibrillar collagen mRNAs was investigated in smooth muscle cells (SMC) in culture. In the absence of FCS, addition of CY222 (100 micrograms/10(6) cells) to postconfluent early passage SMC resulted in a decrease in mRNA level of type III collagen. In contrast, mRNA levels coding for type I collagen, fibronectin and GAPDH (used as control of cellular activity) were not modified. Addition of 5% FCS (without CY222) to the culture medium did not affect mRNA levels of type I and type III collagens nor that of GAPDH. The level of fibronectin mRNA, however, increased in the presence of 5% FCS. In the presence of both 5% FCS and CY222, we observed a decrease in type III collagen mRNA and fibronectin mRNA levels (this level remained, however, above the control value without FCS and the level with CY222 alone). Our results demonstrate that low M(r) heparin fragments can modulate the steady-state levels of type III collagen and fibronectin mRNAs. PMID- 7887981 TI - Characterization of the intracellular distribution and binding in human adenocarcinoma cells of N-(4-azidophenylsulfonyl)-N'-(4-chlorophenyl)urea (LY219703), a photoaffinity analogue of the antitumor diarylsulfonylurea sulofenur. AB - A photoactivatable diarylsulfonylurea, N-(4-azidophenylsulfonyl)-N'-(4 chlorophenyl)urea (LY219703), has been examined as a potential probe to elucidate the intracellular distribution and binding of antitumor diarylsulfonylureas. Our results demonstrated that against the human colon adenocarcinoma cell line GC3/c1, LY219703 is a more potent cytotoxic agent than N-(5-indanylsulfonyl)-N' (4-chlorophenyl)urea (Sulofenur; ISCU), whereas a subline selected for resistance to ISCU was cross-resistant to LY219703, suggesting a similar mechanism of action or resistance. Cellular pharmacology studies showed that [3H]LY219703 concentrated in cells, and that its concentrative accumulation could be inhibited by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), thus indicating that it was similar to other antitumor diarylsulfonylurea (DSU) drugs examined. Accumulation of [3H]LY219703 in cells was progressively decreased by co incubation with increasing concentrations of ISCU, and in cells incubated to steady state with 1 microM [3H]LY219703, ISCU (500 microM) rapidly displaced the photoaffinity analogue. Photoactivation of [3H]LY219703 by UV light (5-30 min) prevented efflux of radiolabeled drug during a 20-min wash in drug-free medium. Subsequent distribution studies showed that 89% of the radiolabel was associated with particulate components, and that approximately 20% of the radiolabel in the 320,000 g pellet could be extracted with acetone. Subcellular distribution showed approximately 6% associated with nuclei, 52% with mitochondria and 26% in the microsomal fraction. The effect of UV photoactivation on the distribution of [3H]LY219703 in soluble and particulate fractions was also examined in GC3/c1 cell preparations sonicated prior to being incubated with [3H]LY219703. A high proportion (83%) of radiolabel associated with the 100,000 g pellet, and distribution between soluble and particulate fractions was not altered by UV irradiation. Specific activities of protein in the 100,000 g supernatant and pellet were 0.186 and 0.537 nmol/mg, respectively. Putative binding species were analyzed by SDS-PAGE. Using SDS-PAGE, ten major binding proteins were identified in 320,000 g pellets from GC3/c1 cells: M(r) 110, 88, 76, 70, 64, 58, 48, 36, 26, and 24 kDa, and at least four of these (88, 70, 64, and 36 kDa) were also detected in mitochondria isolated from cells after photoactivation, or in mitochondrial preparations that were incubated with [3H]LY219703 and photoactivated after isolation from cells. Results suggested that under conditions of SDS-PAGE some dissociation of radiolabel from proteins also occurred. Binding of [3H]LY219703 to a model substrate, bovine serum albumin, and the effect of denaturing conditions used for sample preparation prior to SDS PAGE, showed that relatively mild denaturing conditions (23 degrees, 2 hr) caused significant dissociation of radiolabel from BSA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7887983 TI - Regulation of endogenous noradrenaline release from the bed nucleus of stria terminalis. AB - The bed nucleus of stria terminalis (BNST) contains the highest concentration of noradrenaline (NA) in the brain. Minislices of the ventral portion of the bed nucleus of stria terminalis (vBNST) were used to study the release of endogenous NA. High K+ induced a Ca(2+)-dependent and reserpine-sensitive release of NA. Clonidine (1 microM), an alpha 2-noradrenergic receptor agonist, significantly decreased K(+)-induced release of NA, whereas yohimbine (1 microM), an alpha 2 noradrenergic antagonist, increased this release. N-Methyl-D-aspartate (NMDA), a specific agonist of NMDA-type glutamate receptors, evoked the release of NA from vBNST minislices. In the presence of D-serine (10 microM), an agonist at the glycine site associated with the NMDA receptor, the NMDA effect was significantly higher. Glycine (1 microM) also increased NA release evoked by NMDA. However, glycine exhibited a significant effect by itself, suggesting the existence of strychnine-sensitive glycine receptors in vBNST. Endogenous NA release induced by 40 mM K+ and NMDA was not additive. Thus, vBNST minislices seem to be a good model to study the release of endogenous NA in the CNS. Such NA release in the vBNST is regulated by alpha 2-noradrenergic receptors and by glutamate through NMDA receptors. PMID- 7887982 TI - Phenolic antioxidant-induced overexpression of class-3 aldehyde dehydrogenase and oxazaphosphorine-specific resistance. AB - High-level cytosolic class-3 aldehyde dehydrogenase (ALDH-3)-mediated oxazaphosphorine-specific resistance (> 35-fold as judged by the concentrations of mafosfamide required to effect a 90% cell-kill) was induced in cultured human breast adenocarcinoma MCF-7/0 cells by growing them in the presence of 30 microM catechol for 5 days. Resistance was transient in that cellular sensitivity to mafosfamide was fully restored after only a few days when the inducing agent was removed from the culture medium. The operative enzyme was identified as a type-1 ALDH-3. Cellular levels of glutathione S-transferase and DT-diaphorase activities, but not of cytochrome P450 IA1 activity, were also elevated. Other phenolic antioxidants, e.g. hydroquinone and 2,6-di-tert-butyl-4-hydroxytoluene, also induced ALDH-3 activity when MCF-7/0 cells were cultured in their presence. Thus, the increased expression of a type-1 ALDH-3 and the other enzymes induced by these agents was most probably the result of transcriptional activation of the relevant genes via antioxidant responsive elements present in their 5'-flanking regions. Cellular levels of ALDH-3 activity were also increased when a number of other human tumor cell lines, e.g. breast adenocarcinoma MDA-MB-231, breast carcinoma T-47D and colon carcinoma HCT 116b, were cultured in the presence of catechol. These findings should be viewed as greatly expanding the number of recognized environmental and dietary agents that can potentially negatively influence the sensitivity of tumor cells to cyclophosphamide and other oxazaphosphorines. PMID- 7887984 TI - S-methyl N,N-diethylthiocarbamate sulfone, a potential metabolite of disulfiram and potent inhibitor of low Km mitochondrial aldehyde dehydrogenase. AB - Disulfiram inhibits hepatic aldehyde dehydrogenase (ALDH) causing an accumulation of acetaldehyde after ethanol ingestion. It is thought that disulfiram is too short-lived in vivo to directly inhibit ALDH, but instead is biotransformed to reactive metabolites that inhibit the enzyme. S-Methyl N,N-diethylthiocarbamate (MeDTC) sulfoxide has been identified in the blood of animals given disulfiram and is a potent inhibitor of ALDH (Hart and Faiman, Biochem Pharmacol 46: 2285 2290, 1993). MeDTC sulfone is a logical metabolite of MeDTC sulfoxide. Therefore, we investigated the effects of MeDTC sulfone on the activity of rat hepatic low Km mitochondrial ALDH, the major enzyme in the metabolism of acetaldehyde. MeDTC sulfone inhibited the low Km mitochondrial ALDH in vitro with an IC50 of 0.42 +/- 0.04 microM (mean +/- SD, N = 5) compared with disulfiram, which had an IC50 of 7.5 +/- 1.2 microM under the same conditions. The inhibition of ALDH by MeDTC sulfone was time dependent. The decline in ALDH activity followed pseudo first order kinetics with an apparent half-life of 2.1 min at 0.6 microM MeDTC sulfone. Inhibition of ALDH by MeDTC sulfone was apparently irreversible; dilution of the inhibited enzyme did not restore lost activity. The substrate (acetaldehyde, 80 microM) and cofactor (NAD, 0.5 mM) together completely protected ALDH from inhibition by MeDTC sulfone; substrate alone partially protected the enzyme. Addition of either thiol-containing compound glutathione (GSH) or dithiothreitol (DTT) to MeDTC sulfone before incubation with the enzyme increased the IC50 of MeDTC sulfone by 7- to 14-fold. Neither GSH nor DTT could restore lost ALDH activity after exposure of the enzyme to MeDTC sulfone. Results of these studies indicate that MeDTC sulfone, a potential metabolite of disulfiram, is a potent, irreversible inhibitor of low Km mitochondrial ALDH. PMID- 7887985 TI - The selenium analog of 6-propylthiouracil. Measurement of its inhibitory effect on type I iodothyronine deiodinase and of its antithyroid activity. AB - 6-Propylthiouracil (PTU), a widely used antithyroid drug for the treatment of Graves' disease, is also a potent inhibitor of Type I iodothyronine deiodinase (ID-1). Inhibition of ID-1 was attributed initially to the formation of a mixed disulfide between PTU and a putative cysteine residue at the active site. It has been demonstrated recently that ID-1 is a selenium-containing enzyme, with selenocysteine, rather than cysteine, at the active site. It seemed possible, therefore, that the selenium analog of PTU (PSeU) might be a more potent inhibitor of ID-1 than PTU. To test this possibility, we developed a procedure for the synthesis of PSeU, and we compared PSeU and PTU as inhibitors of ID-1 in a test system containing 125I-rT3, rat liver microsomes, and dithiothreitol. Deiodinase activity was measured by the increase in 125I-iodide. PTU and PSeU were tested at 0.1, 0.3, 1 and 3 microM. Based on results of four separate experiments, the drugs were essentially equipotent as inhibitors of ID-1, although statistical analysis suggested that PSeU may be slightly more potent than PTU. PTU and PSeU were also compared for antithyroid activity in vivo and in vitro. As inhibitors of the catalytic activity of thyroid peroxidase (TPO), the two drugs were essentially equipotent in iodination and guaiacol assays involving measurements made shortly after the addition of H2O2. However, in in vivo experiments with rats, PSeU showed no appreciable inhibition of organic iodine formation in the thyroid, whereas PTU, as expected, was a potent inhibitor. The lack of inhibition of organic iodine formation in vivo by PSeU suggests that, unlike PTU, it is not concentrated by the thyroid gland. In an iodination system in which H2O2 was generated by glucose-glucose oxidase, both PTU and PSeU, when present at 10 microM, acted as reversible inhibitors of iodination. However, when the drug concentration was raised to 50 microM, TPO was inactivated and iodination was irreversibly inhibited. These results suggest that PTU and PSeU inhibit TPO-catalyzed iodination by similar mechanisms. Under the same conditions, the selenium analog of methimazole (another widely used antithyroid drug) does not inactivate TPO. It acts primarily as a reversible inhibitor of TPO catalyzed iodination. PMID- 7887986 TI - Hydrolysis of tetriso by an enzyme derived from Pseudomonas diminuta as a model for the detoxication of O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX). AB - An enzyme termed organophosphorus hydrolase (OPH), derived from Pseudomonas diminuta, had been found previously to hydrolyze the powerful acetylcholinesterase (AChE) inhibitor O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX). This enzyme has now been shown to be correlated with the loss of AChE inhibitory potency (detoxication). OPH also hydrolyzed and detoxified the VX analogue, O,O-diisopropyl S-(2-diisopropylaminoethyl) phosphorothiolate (Tetriso), also a potent AChE inhibitor, about five times faster than VX. The Km for the hydrolysis of the P-S bond of Tetriso was 6.7 x 10(-3) M. OPH also hydrolyzed diisopropylphosphorofluoridate (DFP) 50-60 times faster than Tetriso, and 1,2,2-trimethylpropyl methylphosphonofluoridate (Soman) about seven times faster than Tetriso. DFP was a non-competitive inhibitor of Tetriso hydrolysis, Ki = 8.7 x 10(-4) M. The DFP hydrolysis product, diisopropyl phosphate, was a competitive inhibitor, Ki = 2.3 x 10(-4) M. The rate of detoxication of Tetriso compared with the rate of hydrolysis suggests that OPH may not be totally specific for P-S bond cleavage. OPH was inhibited completely by 1.5 x 10(-4) M 8-hydroxyquinoline-5-sulfonate or 1,10-phenanthroline, both transition element chelators, but inhibited only partially by EDTA, a much more potent chelator. PMID- 7887987 TI - Expression of functional cytochrome P4501A1 in human embryonic hepatic tissues during organogenesis. AB - Investigations with chemical inhibitors and with inhibitory antibodies specific for cytochrome P4501A-catalyzed ethoxyresorufin (ethoxyphenoxazone) O deethylation and 2-acetylaminofluorene (N-2-fluorenylacetamide) ring hydroxylation indicated that cytochrome(s) P450 of the 1A subfamily was functionally expressed in human embryonic hepatic tissues at very early stages (days 50-60) of gestation. Lack of detectable capacity of hepatic microsomal enzymes to catalyze either N-hydroxylation of 2-acetylaminofluorene or O demethylation of methoxyresorufin indicated that functional cytochrome P4501A2 is expressed minimally or negligibly in human embryonic hepatic tissues. By contrast, profound inhibition of the ring hydroxylation of 2-acetylaminofluorene and of the O-deethylation of ethoxyresorufin by 7,8-benzoflavone as well as by anti-cytochrome P4501A1 antibodies indicated the presence of significant levels of functional cytochrome P4501A1 in hepatic microsomes of human embryos. Using the reverse transcriptase-linked polymerase chain reaction with specific oligonucleotide primers, we also detected significant expression of cytochrome P4501A1 mRNA in human embryonic livers. Polymerase chain reaction amplification, cloning and sequencing of the corresponding cDNA provided evidence that the cytochrome P4501A1 mRNA expressed in human embryonic tissues was identical to that expressed in adult human tissues. The results of the study have important implications in terms of the embryotoxic effects of chemicals that are known to be substrates, inhibitors or inducers of cytochrome P4501A1 and to which pregnant women are exposed. PMID- 7887988 TI - Toxicity of cephalosporins to fatty acid metabolism in rabbit renal cortical mitochondria. AB - Cephaloglycin (Cgl) and cephaloridine (Cld) are acutely toxic to the proximal renal tubule, in part because of their cellular uptake by a contraluminal anionic secretory carrier and in part through their intracellular attack on the mitochondrial transport and oxidation of tricarboxylic acid (TCA) cycle anionic substrates. Preliminary studies with Cgl have provided evidence of a role of fatty acid (FA) metabolism in its nephrotoxicity, and work with Cld has shown it to be a potent inhibitor of renal tubular cell and mitochondrial carnitine (Carn) transport. Studies were therefore done to examine the effects of Cgl and Cld on the mitochondrial metabolism of butyrate, the anion of a short-chain FA that does not require the Carn shuttle to enter the inner matrix, and the effects of Cgl on the metabolism of palmitoylcarnitine (PCarn), the Carn conjugate of a long-chain FA that does enter the mitochondrion by the Carn shuttle. The following was found: (1) Cgl reduced the oxidation and uptake of butyrate after in vitro (2000 micrograms/mL, immediate effect) and after in vivo (300 mg/kg body weight, 1 hr before killing) exposure; (2) Cld caused milder in vitro toxicity, and no significant in vivo toxicity, to mitochondrial butyrate metabolism; (3) like Cld, Cgl reduced PCarn-mediated respiration after in vivo exposure, but, unlike Cld, it did not inhibit respiration with PCarn in vitro; (4) the Carn carrier was stimulated slightly by in vitro Cgl but was unaffected by in vivo Cgl; (5) in vivo Cgl had no effect on mitochondrial free Carn or long-chain acylCarn concentrations in the in situ kidney; (6) Cgl increased the excretion of Carn minimally compared with the effect of Cld; and (7) cephalexin, a nontoxic cephalosporin, caused mild reductions of respiration with butyrate and PCarn during in vitro exposure, but stimulated respiration with both substrates after in vivo exposure. CONCLUSIONS: Cgl has essentially the same patterns of in vitro and in vivo toxicity against mitochondrial butyrate uptake and oxidation that both Cgl and Cld have against TCA-cycle substrates. Cld has little or no in vivo toxicity to mitochondrial butyrate metabolism, whereas in vivo Cgl is as toxic as Cld to respiration with PCarn. The greater overall in vivo toxicity of Cgl to mitochondrial FA metabolism, with lower cortical concentrations and AUCs than those of Cld, supports earlier evidence that Cld is less toxic than Cgl at the molecular level. PMID- 7887989 TI - Enhanced phagocytosis activity of cyclic analogs of tuftsin. AB - Cyclic analogs of the physiological immunostimulating peptide tuftsin (Thr-Lys Pro-Arg), cyclo(Thr-Lys-Pro-Arg-Gly) (ctuf-G) and cyclo(Thr-Lys-Pro-Arg-Asp) (ctuf-D), were synthesized based on molecular modeling studies, and assayed for the ability to stimulate phagocytosis by human polymorphonuclear leukocytes. As predicted, the synthesis of ctuf-D resulted in two isomers with the correct molecular mass and amino acid composition. In phagocytosis assays, tuftsin, ctuf G and two isomers of ctuf-D showed the usual bell-shaped activity profiles. The optimum concentration of ctuf-G was 50-fold less than that of tuftsin, whereas the degree of stimulation was similar. One isomer of ctuf-D was almost inactive, and the other ctuf-D exhibited the same degree of phagocytosis as tuftsin but its optimum concentration was 5-fold lower. The enhanced potency of ctuf-G and one isomer of ctuf-D may be due to conformational effects and/or to the possibility that these cyclic peptides are resistant to proteolytic degradation. PMID- 7887991 TI - Effect of nicotine on dopamine uptake in COS cells possessing the rat dopamine transporter and in PC12 cells. AB - The effect of nicotine on the uptake of dopamine (DA) is not completely understood. We studied its effect on PC12 cells and on COS cells transfected with the rat DA transporter cDNA (pcDNADAT1). DA uptake by PC12 cells was inhibited by nicotine in a concentration-related fashion. Treatment of PC12 cells with nerve growth factor (NGF) increased such inhibition. This inhibitory effect was abolished by hexamethonium and mecamylamine, indicating that nicotine acted via the nicotinic acetylcholine (nACh) receptors in PC12 cells. This view is also supported by evidence that acetylcholine (ACh) reduced the uptake of DA in a hexamethonium-, but not atropine-, sensitive fashion. However, nicotine failed to inhibit DA uptake by COS cells possessing the DA transporter. These results suggest that the inhibitory effect of nicotine on DA uptake, when coupled with an nACh receptor leading to an indirect action on the transporter, may play a role in regulating extracellular concentrations of DA. PMID- 7887992 TI - School violence addressed by ESEA. PMID- 7887990 TI - Structure-activity relationships of alkylamines that inhibit rat liver hydroxysteroid sulfotransferase activities in vitro. AB - Tetraalkylammonium salts having n-propyl to n-amyl side chains inhibited rat liver sulfotransferase (ST) activities toward dehydroepiandrosterone and cortisol, but not ST activity toward 2-naphthol, whereas trialkylamines having ethyl to n-amyl side chains inhibited ST activity toward dehydroepiandrosterone, but not ST activities toward cortisol and 2-naphthol. A comparison of I50 values, which represent inhibitor concentration resulting in 50% inhibition of dehydroepiandrosterone ST activity, revealed that the values for the tetraalkylammonium salts were 0.015 to 0.017 mM, whereas the values for the trialkylamines were 0.20 to 0.33 mM. Introduction of hydrophilic groups such as hydroxyl, thiol, nitrile and acetamide groups or substitution by methyl and allyl groups in the alkyl side chains markedly diminished the inhibitory effect of triethylamine. These data indicate that ethyl to n-amyl side chains are a prerequisite for the alkylamine-type inhibitor. Tertiary amine drugs such as imipramine, dimenhydrinate, cyclizine, chlorpromazine and promethazine inhibited ST activities toward dehydroepiandrosterone and cortisol similar to the tetraalkylammonium salts, although the drugs were weaker inhibitors of hydroxysteroid ST activities. These results imply that in addition to trialkylamine side chains, the other portion of the drugs may participate in the inhibition of hydroxysteroid ST activities. PMID- 7887993 TI - Who has hearing, speech, and language problems? PMID- 7887994 TI - Treatment planning using outcome data. Fitting the pieces together. PMID- 7887995 TI - We can do better. Recruiting, retaining, and graduating African American students. PMID- 7887996 TI - Linguistic theories and language interaction. PMID- 7887997 TI - Inuit efforts to maintain face: elements from classroom discourse with Inuit children. PMID- 7887998 TI - Locating communicative competence: the dialogue of immigrant students and American teachers. PMID- 7887999 TI - Understanding language variation: conflict talk in two days cares. PMID- 7888001 TI - Values conflict in a diagnostic team. PMID- 7888000 TI - View of children's word-finding difficulties: disciplinary influences. AB - A consensus was not found among the participants regarding those characteristics that constituted a WFP and how word finding was different from or related to word retrieval problems, some forms of "dysfluency," and "language processing" difficulties. The lack of consistency was seen both within and across disciplines. Instances where there was consistent agreement among members of a discipline must be interpreted cautiously because a relatively small number of participants was involved in the interviews. Further, the results should not be generalized to an assessment of all children with WFPs, because only three children were viewed by the professionals. The findings do suggest, however, dimensions along which problems in interpreting WFPs may occur. The analysis of the clinician interviews and videotape viewing of the three language-impaired children have specific implications for clinicians when diagnosing WFPs in children. First, differences in the clinicians' knowledge of a what word finding is, how it is manifested, what relationship it has to other skills, and how it should be assessed was evident. Such differences in understanding WFPs in children have been described in the literature (Gardner, 1974; German, 1983, 1984; Kail & Leonard, 1986; Lewis & Kass, 1982; Nippold, 1992; Oldfield & Winfield, 1964; Snyder & Godley, 1992). Second, the clinicians frequently made diagnostic assumptions when they admittedly were unsure of their conceptual framework and that of their colleagues. The impact of these assumptions was seen in the clinicians' general lack of agreement in the identification of actual instances of WFPs and in their rankings of those tasks believed to be most helpful in making a diagnosis of a WFP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888002 TI - Conflict talk in a professional meeting. PMID- 7888003 TI - Establishing expertise in communicative discourse: implications for the speech language pathologist. PMID- 7888004 TI - Orchard named 1993 Kelly West recipient. PMID- 7888006 TI - Clinical problem-solving. Still hazy after all these years. PMID- 7888005 TI - Health system reform. Will controlling costs require rationing services? PMID- 7888007 TI - [Extrarenal hemofiltration in pediatric resuscitation]. AB - Peritoneal dialysis, continuous hemofiltration (HF) and continuous hemodiafiltration (HDF) are the most convenient methods for blood purification in pediatric intensive care units. HF is based on the ultrafiltration process and removes not only water but also Na, K, bicarbonate, urea and creatinine with sieving coefficient close to 1. HDF is based on both ultrafiltration and diffusion processes and increases the removal of low molecular weight solutes (urea). These procedures are indicated in: 1) neonates presenting with oligo anuric acute renal failure (ARF) or fluid overload withstanding diuretics or some metabolic diseases; 2) children presenting with ARF, fluid overload or some metabolic disorders, poisonings or shocks. PMID- 7888008 TI - Warm chain for breastfeeding. PMID- 7888009 TI - Omeprazole therapy in resistant reflux disease. PMID- 7888010 TI - Hepatitis E virus and HIV infection in homosexual men. PMID- 7888011 TI - A comparison of the costs and performance of an emergency helicopter and land ambulances in a rural area. PMID- 7888012 TI - Treatment of experimental schistosomiasis mansoni with praziquantel alone and combined with cimetidine. AB - In this work, praziquantel (EMBAY 8440, CAS 55268-74-1), an oral antihelminthic drug effective against the three species of schistosomes pathogenic to man, was tested alone and in combination with cimetidine (CAS 51481-61-9), aH2-receptor antagonist having a known potentiative power when combined with other drugs. Both drugs were tested in different doses and regimen either alone or in combination by giving them to S. mansoni infected Swiss albino mice (100 cercariae/mouse) 7 weeks post infection. Cimetidine was tested in doses of 50, 100 and 200 mg/kg for 2 consecutive days; praziquantel was given in doses of 100 and 500 mg/kg for 2 consecutive days. It was found that the best regimen was that of cimetidine and praziquantel when given simultaneously. Both drugs when given in a dose of 100 mg/kg for 2 consecutive days reduced the total worm load by 84.61%, while a percent reduction of 75.1% and 88.9% was recorded in hepatic and intestinal tissue egg load, respectively. Maximum efficacy was recorded when both drugs were given simultaneously at 200 mg/kg for 2 consecutive days. This regimen completely eradicated all schistosome worms and resulted in the maximum reduction in total tissue egg load (92%). The efficacy of this regimen was nearly the same as that of the full dose of praziquantel (500 mg/kg for 2 consecutive days), gave 100% worm eradication and 95% reduction in total tissue egg load. PMID- 7888013 TI - RU 486 prevents the acute effects of cortisol on glucose and leucine metabolism. AB - Glucocorticoids have deleterious effects on glucose and protein metabolism. RU 486 is an antiprogestin with antiglucocorticoid activity, which could be used to prevent the undesirable metabolic effects of glucocorticoids. A randomized, controlled, double blind study was performed in eight healthy male volunteers who were tested four times: during the iv infusion of cortisol (2 micrograms/kg.min for 5 h) after the oral ingestion of RU 486 (600 mg) or a placebo, and during the infusion of a normal saline solution with placebo or RU 486 ingestion. During each test, a primed continuous iv infusion of D-[6,6-2H]glucose and [1-13C ]leucine was given for the calculation of hepatic glucose production and plasma leucine appearance rate. 13CO2 enrichment in breath was measured for the calculation of leucine oxidation. Plasma concentrations of cortisol, ACTH, insulin, C-peptide, glucagon, and GH were measured at regular intervals. Compared to saline, cortisol infusion increased plasma glucose 5.5 +/- 0.6 vs. 4.7 +/- 0.4 mmol/L; P < 0.01) and leucine (179 +/- 35 vs. 155 +/- 35 mumol/L; P < 0.01) concentrations as well as the leucine appearance rate (2.24 +/- 0.3 vs. 2.0 +/- 0.28 mumol/kg.min; P < 0.05) and oxidation (0.51 +/- 0.22 vs. 0.39 +/- 0.06 mumol/kg.min; P < 0.01), and there was no change in hepatic glucose production. None of the metabolic changes induced by cortisol were seen when cortisol was administered after the ingestion of RU 486. When RU 486 was given before normal saline infusion, plasma glucose concentrations were transiently lower than those after placebo ingestion, as was the hepatic glucose production. No change in insulin, C-peptide, or glucagon was seen between tests. GH concentrations were higher during cortisol infusion, but not when cortisol was administered after the ingestion of RU 486. The following conclusions were reached. 1) RU 486 can suppress the effects of acute hypercortisolemia on glucose and protein metabolism and GH secretion in man. Long term studies are warranted to explore the potential of antiglucocorticoid molecules as preventive agents of the deleterious effects of chronic glucocorticoid administration. 2) RU 486 is useful molecule for studying the metabolic effects of cortisol in man. PMID- 7888014 TI - phyllopod functions in the fate determination of a subset of photoreceptors in Drosophila. AB - phyllopod (phyl) encodes a novel protein required for fate determination of photoreceptors R1, R6, and R7, the last three photoreceptors to be recruited into the ommatidia of the developing Drosophila eye. Genetic data suggests that phyl acts downstream of Ras1, raf, and yan to promote neuronal differentiation in this subset of photoreceptors. Ectopic expression of phyl in the cone cell precursors mimics the effect of ectopic activation of Ras1, suggesting that phyl expression is regulated by Ras1. phyl is also required for embryonic nervous system and sensory bristle development. PMID- 7888015 TI - [Progressive hearing loss--pathophysiology, differential diagnosis, therapy]. AB - Progressive sensorineural hearing loss (SNHL) is still a challenge to the otorhinolaryngologist. It can be solved only by a systematic and interdisciplinary approach to the patient and his disease. Most often an acute onset is observed with a non-linear, sometimes dramatic progress to chronicity and complete deafness. Cardiovascular and rheologic diseases, hereditary disorders, immunological phenomena, hormonal and metabolic derailments, infections, environmental causes like noise, ototoxic drugs and industrial substances and systemic maladies must be included in the diagnostic reflections. Otopathy is an idiopathic hearing loss which cannot be classed with the above mentioned disorders. Wherever possible a causal therapy should be carried out. Symptomatic therapeutic concepts include rheologic medications, corticosteroids or, with all reservation, cytotoxic drugs. Hearing aids should be prescribed in close relation to the dynamic deterioration of the hearing. The timely cochlear implant operation stands at the end of the therapeutic scale. PMID- 7888016 TI - [Noninvasive evaluation of intracochlear pressure. II. Study findings in patients with Meniere's disease, fluctuating deep tone hearing and peripheral vestibular vertigo]. AB - The tympanic membrane displacement technique (TMD) is aimed at evaluating intracochlear and intracranial pressure changes non-invasively. Therefore, the present paper describes the findings in patients with Meniere's disease where an increase in volume of the endolymphatic spaces is discussed. It should be investigated to which extent a change in the intracochlear pressure corresponds to different stages of the disease. It could be described that the intracochlear pressure does change over a certain period of persisting Meniere's, but that there is no extensive increase in intracochlear pressure between the attacks. The glycerol test as well as the acute attack (case report on one patient) are, however, characterised by distinct patterns. The same holds true for the late stage Meniere's. It could be demonstrated that the functional patency of the cochlear aquaeduct in patients with long-term Meniere's history is reduced. This finding is surprising and should be investigated further. In essence, the TMD technique enables to better characterise Meniere patients, but it should not be a tool of routine diagnosis of the disease. In some audiological patients, it can also be beneficially applied (10). PMID- 7888017 TI - [Suitability of various lasers for interventions from the tympanic membrane to the foot plate (Er:YAG, argon, CO2 s.p.--, Ho:YAG laser]. AB - The Erbium:YAG-laser is a good tool for microresection of bone and soft tissue from the ear drum, to the ossicles and extending to the footplate. The mechanism of ablation is based on the fact that the emission of infrared light is of the same wavelength at which water has its peak of optimal light absorption. 14% of bone is water, just sufficient force for ablation. At 50 mJ impulses the temperature in the centre stays below the coagulation point. 500 impulses of 50 mJoule definitely remain below the acoustic risk. In 44 guinea pigs 500 x 50 mJ caused a temporal threshold shift of maximal 38 dB at 2000 cps which recovered after 90-135 min. In 60 tympanoplasties neither tinnitus nor audiological side effects of the laser application were measured. The ear drum is perforated by 1 ( 3) impulses. This can be done even in children after superficial anaesthesia (2% pantocaine drops) to drain the middle ear. The laser perforation of 0.3 mm [symbol: see text] will close after a day and has to be re-opened in the office to avoid tubes. We do not yet know how often general anaesthesia and removal by suction of too viscous mucus remain nevertheless necessary. With the Er:YAG laser parts of the ossicles can be cut out of the intact chain, without contact and trauma, nearly without loss of bone tissue. This allows better radicality in removing cholesteatomas or scars with less destruction. 500 impulses of 50 mJ ablate 32 mg of bone, i.e. the weight of an incus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888018 TI - [Animal experiment studies on CO2 laser stapedotomy]. AB - Experiments were performed in guinea pigs to clarify which, if any, of the CO2 lasers used can damage the inner ear on application of the laser parameters required for stapedotomy. A further aim was to determine their application safety. The basal convolution of the guinea-pig cochlea was chosen as the application site, since its thickness is similar to that of the human stapes base. We examined the laser effect in connection with perforation of the basal convolution and subsequent application in the open cochlea. Acoustic evoked potentials (compound action potentials [CAP]) yielded information on inner-ear function. Animals without laser treatment were used as controls. Perforation of the basal convolution and laser applications in the open cochlea with the same parameters did not lead to a measurable CAP alteration with the CO2 cw laser (power: 8 W, pulse duration: 50 ms, power density: 3200 W/cm2). An increase of the laser power to 15 W (power density: 6000 W/cm2) and of the pulse duration to 200 and 500 ms (energy: 3 J and 7.5 J) caused partly irreversible CAP alterations; finally, no potential could be recorded any more at a maximal laser power and pulse duration (15 W and 500 ms). Examination of high power densities (40,000 and 60,000 W/cm2) through reduction of the laser beam diameter to 180 microns yielded comparable results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888019 TI - [Expression of calgranulin A and B in middle ear cholesteatoma]. AB - Cholesteatoma epithelium is characterised by a keratinocyte dysregulation with a hyperproliferative growth and altered differentiation. Keratinocytes with a reduced turnover time show an increase of calcium binding proteins like calgranulin A and B. These proteins are highly linked with the modulation of cell growth and differentiation. The expression of calgranulin A and B was studied immunohistochemically using the monoclonal antibody F12 on cryosections of cholesteatoma biopsies. Normal skin served as control. The staining in normal skin was confined to the highly proliferative activated follicular keratinocytes, whereas most cholesteatomas showed a staining of all cell layers of the epithelium. Our findings show that the keratinocyte dysregulation of the cholesteatoma epithelium is reflected by variations of the expression of calcium binding proteins. PMID- 7888020 TI - [Surgical treatment of the obliterated tympanic cavity with autologous mucous membrane cell suspension]. AB - 5 patients suffering from high-grade sound conduction deafness due to extensive adhesion process on both ears underwent tympanoplasty on one of the ears. The missing tympanic mucosa was replaced by an autologous cell suspension prepared from mucosa of the maxillary sinus. 6-12 months after re-epithelialisation of the tympanic cavity, reconstruction of the ossicular chain was performed using glasionomer cement prostheses (IONOS). 3 patients showed an improvement of hearing after transplantation of the isolated mucosal cells and following replacement of auditory ossicles. One patient had good improvement of hearing already after reconstruction of the tympanic cavity. In one case reobliteration of the tympanic cavity occurred. The clinical results confirm that using mucosal cell suspensions for reepithelisation of an obliterated tympanic cavity is yet another successful step forward in reconstructive surgery of the middle ear. PMID- 7888021 TI - [Effect size on resonance of the outer ear canal by simulation of middle ear lesions using a temporal bone preparation]. AB - By means of a model of the external and the middle ear it is possible to simulate various, exactly defined pathological conditions of the middle ear and to describe their influence on ear canal resonance. Starting point of the investigations are fresh postmortem preparations of 8 human temporal bones with an intact ear drum and a retained skin of the ear canal. The compliance of the middle ear does not significantly differ from the clinical data of probands with healthy ears. After antrotomy it is possible to simulate pathological conditions of the middle ear one after the other at the same temporal bone. The influence of the changed middle ear conditions on ear drum compliance, ear canal volume and on the resonance curve of the external ear canal was investigated. For example, the middle ear was filled with water to create approximately the same conditions as in acute serous otitis media. In this middle ear condition a significant increase of the sound pressure amplification was found, on an average by 4 decibels compared to the unchanged temporal bone model. A small increase in resonance frequency was also measured. The advantages of this model are the approximately physiological conditions and the constant dimensions of the external and middle ear. PMID- 7888022 TI - [Syringocystadenoma papilliferum of the outer ear canal]. AB - Ceruminomata are tumours spreading from the ceruminous glands of the external auditory canal. Since 1894 190 cases have been described, but nomenclature is still confusing to some extent. Syringocystadenoma papilliferum is a special subgroup. 189 cases are reported in the literature; 11 tumours have been observed in the auditory canal. A further case is reported in this paper. PMID- 7888023 TI - [Surgery of cholesteatoma of the ear canal]. AB - Aseptic necrosis and cholesteatoma of the external auditory canal can be stages of the same pathological entity. The majority of these patients suffered from symptoms similar to those of external otitis. It is suggested that minor mechanical trauma, e.g. cotton lip swabs, plays a role in the pathogenesis of external ear canal cholesteatoma. During the last 10 years we have been surgically treating 22 patients with diagnosis of aseptic necrosis and cholesteatoma of the bony external auditory canal. All 22 patients registered significant postoperative improvement. PMID- 7888024 TI - [Cerumen from the anthropologic viewpoint]. AB - The dimorphism of cerumen was first discovered by Kishi in 1907. There are two types of cerumen which differ in colour and consistency: the flocky and gray dry cerumen and the sticky yellow to brown wet cerumen. The comprehensive review of the frequency of the different cerumen types and their geographical distribution result in evidence for the dry type as a distinguishing feature of the mongoloid peoples (including the American Indians). The frequency of the wet cerumen prevails significantly in the Negroid (Congoid) and the Europoid (Caucasoid) population. Intermediate incidence data are due to racial intermixture. PMID- 7888025 TI - [Leiomyosarcoma of the temporal bone]. AB - This is a report on a patient of 74 years of age presenting with ear pain and bleeding granulations on his tympanic membrane. X-ray of the mastoid revealed partial destruction of the bone structures and reduced pneumatisation. A tumour that was mainly located in the temporal bone was surgically removed and proved to be a leiomyosarcoma. This is the first case of a leiomyosarcoma of the temporal bone to be described. Differential diagnosis and therapy of this tumour are discussed. PMID- 7888026 TI - [Vascular, inflammatory and tumorous lesions of the temporal bone and cerebellopontile angle: applications of magnetic resonance tomography]. AB - Advances in high resolution magnetic resonance imaging (MRI) allow the evaluation of the cerebellopontine angle and temporal bone. The purpose of our study was to demonstrate pathological and anatomical aberrations of cerebral arteries in relation to clinical symptoms. The study was carried out on a 1T MR whole body scanner (Impact, Siemens, Erlangen, Germany), using a head coil, a pre- and postcontrast ("Magnevist", Schering, Berlin, Germany) T1-weighted 2D-FLASH sequence and a T2-weighted turbo-spin echo sequence. We examined 22 patients suffering from asymmetric hearing loss, pulse-synchronous tinnitus, hemifacial spasm or facial palsy. The problem of a clear differentiation of meningiomas and acoustic neurinomas by means of MRI is discussed. We identified aberrant AICAs at the cerebellopontine angle in close contact with the V., VII. and VIII. cranial nerve. Inflammatory lesions of the facial and vestibulocochlear nerve were visualised successfully. The potential of the pre- and postcontrast 2D-FLASH sequence for the detection of a wide range of different lesions in the cerebellopontine angle and the temporal bone in MRI of the head was demonstrated. PMID- 7888027 TI - [Mucoserotympanon of the adult]. PMID- 7888028 TI - [The unrecognized sudden deafness--on the question of obligation to consult an ENT physician in ear manifestations within the scope of inpatient treatment]. PMID- 7888029 TI - [Vestibular lesion in sudden deafness: a prognostic criterium for therapeutic success]. AB - The influence of vestibular dysfunction on severity of initial hearing loss and success of therapy was evaluated in a retrospective study with 142 patients suffering from idiopathic sudden hearing loss. In 48% of these patients combined cochleovestibular disorders were found. In this group mean hearing loss was significantly higher (45 dB versus 32 dB) and hearing recovery after therapy (25% versus 38%) less pronounced. 83% of patients with high grades of vestibular disorders (Vestibular Index: > or = 9) showed a decrease of hearing function between 50 dB and 130 dB compared to 32% in the group with signs of low vestibular dysfunction. Additional vestibular lesion in patients with sudden deafness can be used as a criteria for prognosis. High grade vestibular lesion reduce the probability of complete hearing recovery. PMID- 7888030 TI - Structural characterization of an (NZB x NZW)F1 mouse-derived IgM monoclonal antibody that binds through V region-dependent interactions to murine IgG anti DNA antibodies. AB - Among B/W-derived IgM mAb, 12.5H was selected because of its ability to recognize, in solid phase ELISAs, IgG mAb with DNA-binding activity. mAb 12.5H bound preferentially to IgG2a mAb and did not react with B/W- or BALB/c-derived IgG2a mAb with no DNA-binding activity, suggesting V region-mediated interactions. mAb 12.5H also bound to IgG2a isolated from the sera of old B/W mice but did not react with Ig present in the sera of young B/W (< 6 months) or BALB/c mice. Further analysis of IgM/IgG interaction showed that the binding of 12.5H to IgG polyclonal anti-DNA antibodies could be inhibited by DNA and that mAb 12.5H bound to the F(ab')2 fragments of B/W-derived IgG2a anti-DNA mAb, demonstrating that the interaction occurred through the variable regions of the molecules. When the antigen-binding capacity of mAb 12.5H was evaluated, it was demonstrated to bind to self-antigens such as myosin, actin, tubulin and histones, to bind poorly to ssDNA and not to react with dsDNA. mAb 12.5H gave a cytoplasmic staining pattern by indirect immunofluorescence on HEp-2 cells. Nucleotide sequence analysis of the H and L V genes showed features previously demonstrated to be recurrent in two categories of SLE autoantibodies, i.e. arginine residues in the VHCDR3 and at position 96 on the light chain, both considered to be characteristic of antibodies reacting with dsDNA and acidic amino-acid residues in VHCDR2 reported to be frequent on antihistone antibodies. Taken together, these results show that the B/W mouse repertoire contains IgM autoantibodies: (i) that react in an idiotypic manner with DNA binding antibodies and (ii) that, because of structural characteristics, may constitute the common precursor of different categories of SLE autoantibodies, and the prototype of the idiotypically connected SLE autoantibodies accounting for the production of autoantibodies upon immunization with cognate idiotype and the experimental model of cross-idiotype-induced lupus. PMID- 7888031 TI - Coxsackie B1 virus-induced murine myositis: a correlative study of muscular lesions and serological changes. AB - We investigated the role of humoral factors in the pathogenesis of Coxsackie B1 virus-induced murine myositis (CB1-myositis). At 2, 4 and 8 weeks after inoculation, serum was studied for circulating immune complexes (CIC) (Raji-cell assay), haemolytic complement activity (CH50 titre) and anticytoplasmic autoantibodies (Western blotting, immunoprecipitation) in relation to degree of mononuclear cell infiltration and muscle fibre necrosis. At 2, 4 and 8 weeks, cell infiltration correlated positively to muscle fibre necrosis. From 2 weeks on, moderate quantities of CIC were found in nearly all CB1-inoculated mice, but without correlation to histological changes. Except for a positive correlation of CH50 titre to muscle necrosis at 4 weeks (r = 0.60; P = 0.02), CH50 titres did not correlate to muscle lesions. Anticytoplasmic and other known autoantibody specificities were absent. In conclusion, first, in CB1-myositis CIC occurred from 2 weeks on, but no correlative evidence was found for their involvement in pathogenesis, neither for that of complement nor for anticytoplasmic autoantibodies. Secondly, cell infiltration correlated positively to muscle necrosis, underscoring the importance of cellular mechanisms. Thus, our data do not support, or conclusively exclude, a role for humoral processes in CB1 myositis. PMID- 7888032 TI - Chronicity of arthritis induced with homologous type II collagen (CII) in rats is associated with anti-CII B-cell activation. AB - DA rats develop chronic arthritis after immunization with native rat type II collagen (CII) emulsified in incomplete Freund's adjuvant (IFA) (= collagen induced arthritis, CIA). The same rat strain develops an acute, self-limited form of arthritis after injection with IFA alone (= oil-adjuvant-induced arthritis, OIA). The induction of a chronic course of arthritis, as well as an anti-CII antibody response, was dependent on the dose of CII; 30 micrograms induced a self limited disease course and no B-cell response, while 150 micrograms induced a chronic disease course and a strong B-cell response. Immunization with denatured rat CII induced only acute arthritis, similar to OIA. To investigate why IFA or denatured CII/IFA induced only acute disease while native CII/IFA induced chronic disease, we analysed the immune responses to CII. Both native and denatured CII induced a weak but significant autoreactive T-cell response while only native CII induced a strong B-cell response to CII. IFA did not produce a significant immune response to CII. Interestingly, rats that had developed acute arthritis after immunization with denatured CII/IFA were vaccinated against CIA, but not rats that had developed arthritis induced with IFA only. Rats vaccinated against CIA after pretreatment with denatured CII/IFA had an anti-CII antibody response that was almost eliminated. In addition, pretreatment of rats with denatured or native rat CII in olive oil, which does not induce arthritis, vaccinated against a subsequent induction of arthritis with native rat CII. Again, the vaccination suppressed the anti-CII B-cell response. We suggest that activated B-cells, reactive with conformational epitopes on CII, are of importance for the chronic development of CIA. PMID- 7888033 TI - Glipizide-induced prevention of diabetes and autoimmune events in the BB rat. AB - To determine whether glipizide, a sulfonylurea, can prevent diabetes in the diabetic-prone BB rat model, rats were studied from 35 to 240 days of age. Treated animals received oral glipizide (10 or 100 mg/kg/day) from 35 to 200 days of age, and control rats received oral placebo. From 80 to 135 days of age at both drug doses, glipizide decreased the incidence of diabetes, thus delaying disease onset (P < 0.02). At the higher dose of glipizide, a diabetes preventive effect was observed (P < 0.025). There were no significant differences in body weights between the treated and control groups. At 240 days, i.e. 40 days after stopping glipizide and placebo treatments, diabetes incidence remained stable in the two groups; thus the effect of glipizide persisted after discontinuation of the drug. Serum glucose and insulin levels measured at 90 and 200 days did not reveal differences between the glipizide treated and control groups. To determine whether the sulfonylurea affected autoimmune events, the prevalence and severity of islet inflammation were examined. In glipizide-treated BB rats at 240 days, only 44% of rats had islet inflammation compared to 86% in the control group (P < 0.01). At both 90 and 240 days the severity of islet inflammation was decreased in the glipizide treatment groups compared with the control groups (P < 0.01). These data indicate that glipizide (a) prevents diabetes in the diabetic-prone BB rat strain, (b) decreases the prevalence and severity of islet inflammation even after drug withdrawal and (c) may dampen autoimmune events leading to diabetes onset. PMID- 7888034 TI - Effect of CD28 antibody on T cells from patients with systemic lupus erythematosus. AB - CD28 is a 44-kDa glycoprotein that contributes to T cell activation and proliferation. To elucidate the functional role of CD28 in T cell proliferation and IL-2 production in SLE, we studied its effects in cells from untreated patients with active (n = 10) or inactive disease (n = 10) as compared with normal subjects. Mean percentages of CD4+ CD28+ and CD8+ CD28+ T cells were decreased in SLE patients (P < 0.01). SLE patients had significantly decreased absolute CD8+ CD28+ T cells. To investigate whether CD28 antibody affects T cell proliferation, we stimulated peripheral blood T cells from SLE patients and normal controls with anti-CD28, anti-CD3 and/or Interleukin-2 (IL-2) during 3 days of culture. We found that T cells from SLE patients had significantly higher responses to CD28 than did cells from normal controls. This effect was higher in cells from patients with active disease than in those with inactive disease. Conversely, IL-2 had no significant effect on the proliferative response of SLE T cells. However, when it was used for co-stimulating with anti-CD28, there was an increase in the secretion of IL-2 which was greater in the cells of patients with active disease. Thus, on average, there was an 81% increase in the production of IL-2 in T cells from patients with active SLE, 48% in those from patients with inactive disease and 40% in T cells from healthy controls, as compared with the production in response to stimulus by anti-CD3 or with anti-CD3 and anti-CD28. Lymphocytes from patients with active disease showed increased gene expression of CD28 when compared with normal subjects. These data suggest that CD28 might play a central role in the defective immune response observed in SLE patients. PMID- 7888035 TI - Antibodies to collagen: comparative epitope mapping in women with silicone breast implants, systemic lupus erythematosus and rheumatoid arthritis. AB - Women with silicone breast implants have a significantly increased frequency of antibodies to collagen types I and II. To characterize the specificity of these antibodies, 70 women without a specific autoimmune disease, according to the criteria of the American College of Rheumatology, but who had silicone breast implants were studied for the presence of serum antibodies to native and denatured human types I and II collagen by ELISA. Positive sera were further studied by immunoblotting using peptides derived by cyanogen bromide digestion of the collagens. Samples of 82 women with systemic lupus erythematosus (SLE), 94 women with rheumatoid arthritis (RA), and 133 healthy controls were studied concurrently. There was a high frequency of autoantibodies to collagen in each of the study groups when compared to the healthy controls. However, and of particular interest, the epitope specificity of the autoantibodies differed markedly. Sera from women with silicone implants reacted strongly in an individual-specific manner with multiple peptides of type I collagen, whereas sera from women with SLE and RA reacted only weekly with a restricted range of peptides of type I collagen. Sera from women with RA reacted strongly with multiple peptides of type II, whereas sera from women with silicone implants or SLE reacted only weakly. The reactivity of women with silicone implants suggests that silicone or its biodegradation products can act as adjuvants in situ to enhance the immunogenicity of type I collagen, or protein-silicone conjugates. PMID- 7888036 TI - Evaluation of islet-specific autoantibodies in Japanese patients with insulin dependent diabetes mellitus: a comparison between autoantibodies to glutamic acid decarboxylase, autoantibodies to 64 kDa islet cell protein and islet cell antibodies. AB - Autoantibodies to glutamic acid decarboxylase (GAD), autoantibodies to 64 kDa islet cell protein and islet cell antibodies (ICA) were measured in 79 Japanese patients with insulin-dependent diabetes mellitus (IDDM). The overall prevalences of GAD antibodies, 64K antibodies, and ICA in these patients were 69.6% (55/79), 48.1% (38/79), and 46.8% (37/79), respectively. However, in a subset of these patients with recent onset IDDM (< 1 year) the prevalences of GAD antibodies, 64K antibodies, and ICA were 78.8% (26/33), 66.7% (22/33), and 78.8% (26/33), respectively. Furthermore, the prevalences of GAD antibodies, 64K antibodies, and ICA were significantly decreased in patients with long standing diabetes at 60.9% (28/46), 34.8% (16/46), and 23.9% (11/46), respectively. However, when these patients were divided into two groups by the presence or absence of organ specific autoimmune disease (OSAD), the mean levels of GAD antibodies and ICA in the patients who gave a positive result were significantly higher in patients with OSAD (397 units and 98 JDF units, respectively) than in patients without OSAD (74 units and 39 JDF units, respectively). These results demonstrate that it is important to evaluate the prevalences and levels of islet-specific autoantibodies when considering disease duration and co-existence of autoimmune disease in patients with IDDM. PMID- 7888037 TI - Attachment of monophosphoryl lipid A (MPL) to cells and liposomes augments antibody response to membrane-bound gangliosides. AB - Antibodies to gangliosides are found in low levels in normal individuals, and attempts to augment their production have had limited success. Murine studies suggest that the antibody response to membrane-bound cryptic antigens, such as phospholipids and gangliosides, can be induced and augmented by attaching lipid A to membranes. Therefore, we assessed the ability of monophosphoryl lipid A, a non toxic derivative of lipid A, to augment antibody response against membrane associated gangliosides. Anti-ganglioside antibodies were IgM after the first and second immunizations; in contrast, anti-phospholipid antibodies were IgM after the first immunization and IgG after the second immunization. Mice (BALB/c) immunized with MPL-attached human cells as well as mice (C57BL/6J) immunized with MPL-attached syngeneic tumor cells (B16 melanoma) produced a significant IgM response. Mice (C57BL/6J) immunized with MPL-attached liposomes containing GM3 developed significantly higher IgM responses than those immunized with purified gangliosides, MPL or MPL-free B16 cells. However, the antibody response after immunization with MPL-GM3-liposomes is similar to that after immunization with MPL-attached tumor cells, even though the MPL-liposomes contained a 27-fold higher level of gangliosides than the tumor cells. Our results emphasize that co expression of MPL with membrane-bound gangliosides is necessary to augment the anti-ganglioside antibody response. These findings may shed light on the elevated titers of anti-ganglioside IgM antibodies found in patients with motor neuron diseases, various neuropathies and classical ALS, and are relevant to clearance of circulating immunosuppressive gangliosides in cancer patients. PMID- 7888038 TI - Adoptive transfer of autoimmune diabetes mellitus to athymic rats: synergy of CD4+ and CD8+ T cells and prevention by RT6+ T cells. AB - We describe the induction and prevention of autoimmune insulin dependent diabetes mellitus (IDDM), and its pathological substrate, insulitis, in congenitally athymic nude rats following injections of major histocompatibility complex (MHC) compatible lymph node T cells. The cells capable of adoptive transfer of autoimmunity were obtained from diabetes resistant (DR) BB rats that had been rendered hyperglycemic by in vivo depletion of the RT6+ regulatory T cell subset. We first established that our adoptive transfer assay system is cell dose- and time dependent and therefore amenable to quantitative analysis. It was also observed that both CD4+ and CD8+ T cells are required for efficient transfer of autoimmunity. The data indicate that, as in the NOD mouse, a synergistic interaction between CD4+ and CD8+ T cells is important for beta cell destruction. Finally, we demonstrated that the admixture of equal numbers of lymph node T cells, 60% of which were RT6+, from intact, non-diabetic DR rats prevented the adoptive transfer of IDDM mediated by diabetogenic T cells from RT6-depleted DR BB rats. We conclude that an equilibrium between autoreactive and regulatory cells determines the expression of autoimmunity in the DR-BB rat and in the adoptive transfer of diabetes in quantitative analytical systems. PMID- 7888039 TI - Analysis of the spontaneous T cell response to insulin in NOD mice. AB - Insulin-specific T cells have been found to be present in high frequency among nominally islet-cell-specific T cells in the islet infiltrates that accumulate in NOD mice. In a previous report in which clones obtained from 7- and 12-week-old mice were examined, we identified a 15-residue peptide of the B chain as the dominent epitope for this response. Despite the fact that the response to insulin appears to be directed toward this single peptide, diverse TCR V beta usage was observed. That insulin-specific T cells contribute to beta cell damage is suggested by the fact that all clones tested could mediate beta cell destruction upon adoptive transfer. In the present report we extend this examination of insulin-specific T cells to lines and clones established from mice ranging in age from 4-12 weeks. These clones were found to be very similar to those from 7- and 12-week-old mice. The response was directed to the same peptide and most were found to produce IFN gamma, but none produced IL-4. PMID- 7888040 TI - Administering glutamic acid decarboxylase to NOD mice prevents diabetes. AB - Type 1 diabetes is the result of an ongoing autoimmune response to specific proteins expressed by the insulin producing beta cells. Recently, a number of beta cell autoantigens have been identified. However, their role in mediating the diabetogenic response is not known. Here we assess the relative importance of a panel of beta cell autoantigens in the disease process. The approach was to inhibit T cell proliferation to a given autoantigen by either i.t. or i.v. injections, and then determine the effect this had on the diabetogenic response. We show that administering murine glutamic acid decarboxylase (GAD) to 3-week-old NOD females can reduce the frequency of insulitis and prevent the onset of diabetes. In contrast, carboxypeptidase H or peripherin do not induce a similar protective effect, suggesting that GAD has a critical role in the diabetogenic response. These results also suggest that GAD may provide a useful target for antigen-specific immunotherapy. PMID- 7888041 TI - The thymus as a site for evaluating the potency of candidate beta cell autoantigens in NOD mice. AB - Intrathymic (i.t.) injection of islet cells or whole islets retards development of insulin dependent diabetes mellitus (IDDM) in spontaneous animal models of the disease. Protection of 4-week-old prediabetic NOD/Lt female mice from subsequent IDDM development was specific for the it route of administration since intraperitoneal injection of an equal number of syngeneic islets failed to retard IDDM. The protective effect of i.t. injection of islet cells was compared with the effect of i.t. injection of syngeneic peritoneal exudate cells, NIT-1 cells, bovine serum albumin (BSA), ABBOS peptide, a 52 kDa islet cell membrane protein, various synthetic peptides from human glutamic acid decarboxylase (GAD) and a Coxsackievirus B4-derived peptide with homology to GAD. Interestingly, only a GAD derived peptide containing sequence homology to Coxsackie-virus B4, and the corresponding Coxsackievirus B4-derived peptide, delayed IDDM onset. To establish the immunological mechanism underlying the reduced IDDM incidence following i.t. injection of islet cells, adoptive transfer of splenic leukocytes into NOD scid/scid mice was performed. Splenic leukocytes from i.t.-injected non-diabetic females transferred IDDM into NOD-scid/scid recipients, but more slowly than splenocytes from unmanipulated, diabetic (control) donors. Co-transfer of 1:1 mixtures of splenic leukocytes from it islet-injected (and diabetes-free) NOD/Lt females and from untreated NOD/Lt diabetic donors produced IDDM as rapidly as splenocytes from diabetic donors injected alone. Hence, any peripheral suppression generated in i.t.-protected females was not sufficiently strong to prevent IDDM transfer by committed T-effector cells from the diabetic donors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888042 TI - GAD65 autoantibodies increase the predictability but not the sensitivity of islet cell and insulin autoantibodies for developing insulin dependent diabetes mellitus. AB - The clinical onset of insulin-dependent diabetes (IDD) can be predicted by determination of autoantibodies to several pancreatic-islet cell antigens. Islet cell autoantibodies (ICA) and insulin autoantibodies (AA) are most commonly used. We have developed a recombinant human glutamic acid decarboxylase (GAD65) radioimmunoassay and measured autoantibodies to GAD65 (GAD65A) in the sera of 73 documented prediabetic individuals, 76 newly-diagnosed patients, 103 relatives of IDD probands at increased risk for the development of IDD because they were positive for ICA and/or IAA, 72 ICA and IAA negative relatives, and 207 healthy controls. Our data demonstrate that GAD65A are strongly associated with the currently established autoantibody markers of IDD. Their presence in prediabetic subjects with only ICA or IAA enhances their risk for progression to IDD, yet does not much enhance the screening sensitivity already available through conventional ICA and IAA for IDD prediction. PMID- 7888043 TI - Do glutamic acid decarboxylase antibodies improve the prediction of IDDM in first degree relatives at risk for IDDM? AB - To determine whether the predictive value of islet cell antibodies (ICA) and insulin autoantibodies (IAA) is increased by measurement of glutamic acid decarboxylase antibodies (GADAb) in first-degree relatives of patients with insulin-dependent diabetes mellitus (IDDM), we measured GADAb in those developing IDDM and in relatives found to be ICA- or IAA-positive in our family screening study. First-degree relatives (n = 2904) were followed for 2.4 (median, range 0.04-5.8) years. Of the subjects developing IDDM, 11/14 (78%) had ICA > or = 20JDF units, 1/14 (7%) had IAA > or = 100 nU/ml and 6/14 (43%) had GADAb (> or = 460 nU/ml, measured by precipitation of enzymatic activity). Of the four subjects with ICA < 20 and IAA < 100 nU/ml who developed IDDM, one had elevated GADAb. Significant inhibition of GAD enzymatic activity by serum immunoglobulins, a potential cause of false-negative results in our immunoprecipitation assay, was not detected in seven subjects who developed IDDM in the absence of GADAb. Sixty nine of the 2904 subjects with ICA > or = 20 or IAA > or = 100 were followed for 3.1 (median range 0.1-5.4) years. Survival analysis showed that diabetes-free survival in this group was not influenced significantly by GADAb positivity. In conclusion, GADAb in the absence of ICA and IAA are uncommon in first-degree relatives who progress to IDDM and the presence of GADAb does not increase the risk for IDDM in ICA- or IAA-positive relatives. PMID- 7888044 TI - A universal model of antibody prediction (MAP) of type 1 diabetes in children. AB - The majority of children who develop Type 1 diabetes under the age of 10-years old show islet cell antibodies at levels of 40 or more units. Those who have lower levels (10- < 40) usually have co-existent insulin autoantibodies. Of these children 85% have these criteria. When these criteria were applied to large groups of similarly aged children who were either first degree relatives of a type 1 diabetic or had no such family history, 3.8% and 0.38% respectively showed these criteria. The observed sensitivity of these characteristics in identifying children who develop diabetes in the subsequent 5 years is 79% for both groups. The calculated expected incidence of disease in the subsequent 10 years for these two groups is 2.15% and 0.215% respectively. This model of autoantibody prediction of diabetes in children thus applies equally well in terms of sensitivity and specificity to those with and without a family history of diabetes. PMID- 7888045 TI - High risk HLA-DR/DQ genotypes for IDD confer susceptibility to autoantibodies but DQB1*0602 does not prevent them. AB - Although HLA class II genes are important in insulin-dependent diabetes (IDD), their influence on the expression of IDD-associated autoantibodies (aAb) is unclear. We compared HLA-DRB1 and DQB1 gene frequencies in several Caucasian groups: 191 normal controls, 378 IDD patients, and 357 non-diabetic relatives of which 250 had no aAb, 107 had at least one aAb (79 ICA+, 31 GAD65+ and 49 IAA+), and 23 had both ICA+ and IAA+. We found that the frequencies of DR3/4 or DQB1*0201/0302 heterozygotes were significantly higher in aAb+ relatives compared to aAb- relatives. The frequencies of DR4/4 or DR4/X (X = non 3 or 4) and DQB1*0302/X (X = 0201 or 0302) in aAb+ relatives were not different from the aAb- relatives (which were enriched for these haplotypes), but were significantly higher than normal controls. The frequencies of DR3/X or DQB1*0201/X were decreased in both aAb+ relatives and IDD patients. Interestingly, the dominant IDD-protective DQB1*0602 allele allowed the development of individual aAbs (10% of ICA+ and 8% IAA+ relatives had the allele), but was not observed in any high risk double aAb+, or GAD65Ab+ relatives. The latter finding was similar to that in our patients with IDD, in that only two of them (0.5%) had a DQB1*0602 allele. In conclusion, HLA-encoded susceptibilities to disease-relevant autoantibody production and IDD are concordant with the susceptibility alleles, but discordant for the protective DQB1*0602. Thus HLA genotyping for DQB1*0602 would impact on the selection of aAb+ relatives for disease prevention trials. PMID- 7888046 TI - Donor-specific cytotoxicity induced by allogeneic intestinal epithelial cells in a sponge matrix model. AB - Small intestinal epithelial cells (IEC) constitutively express MHC class II molecules. However, little is known about the role of IEC in intestinal allograft rejection. The present study examined whether IEC can induce the development of cytotoxic T cells in vivo using a sponge matrix model. IEC isolated from ACI (RT1a) rats were injected into polyurethane sponges implanted i.p. in Lewis (RT1(1)) rats. Sponge grafts with ACI splenocytes or Lewis IEC were used as controls. The sponge grafts were removed and sponge-infiltrating cells (SIC) were harvested on post-operative days (POD) 7, 10, and 14. The phenotype of SIC was determined by FACS analysis and the cell-mediated cytotoxicity was measured using a chromium relapse assay. Non-specific inflammatory cells accumulated in the IEC sponge allografts during the first 10 days. By POD 14, however, 61% of SIC were T lymphocytes and 36% expressed cytotoxic T cell marker (OX-8). The cytotoxicity in IEC sponge allografts was detectable on POD 7 and POD 10, and markedly elevated on POD 14. The cytotoxicity induced by allogeneic splenocytes appeared in the sponge grafts on POD 7, peaked on POD 10, and declined thereafter. The allospecific cytotoxicity induced by IEC was dependent on host macrophages as pretreatment of animals with gadolinium, a rare earth metal that inactivates macrophages, abrogated the induction of cytotoxicity. We conclude that: (1) the migration and maturation of cytotoxic T cells can be induced in vivo by IEC and (2) IEC may contribute to the increased severity of intestinal rejection through interaction with macrophages. PMID- 7888047 TI - Fulminant hepatic failure post liver transplantation: clinical syndromes, correlations and outcomes. AB - This paper reports the clinical syndrome of fulminant hepatic failure (FHF) following liver transplantation. FHF was defined as the sudden onset of liver failure [encephalopathy and prolonged International Normalised Ratio (INR)] without arterial thrombosis in the setting of a liver allograft. FHf post transplant was seen in 8/154 (5.2%) adult patients undergoing transplantation. These eight patients developed a clinical syndrome characterised by: (a) a rapid rise in ALT levels to above 1000 U/l (mean maximum 1600 U/l), (b) a sudden increase in the INR to above 5 (mean maximum 5.6), (c) the development of high fever, (d) the persistence of thrombocytopenia (mean nadir 40 x 10(9)/dl), (e) a progressive rise in the bilirubin (mean maximum 400 mumol/l) and (f) the development of hepatic encephalopathy. In seven cases this syndrome occurred following good initial graft function at day 6 post (mean)-transplant. In one case the above syndrome developed immediately after liver transplantation. Four of the eight patients developed multiorgan failure associated with systemic acidosis (mean pH 6.84). All of these patients died (mean day 11). Four patients developed systemic alkalosis. Two of these four patients underwent successful retransplantation (on days 12 and 13) and remain alive at a mean of 11 months post-transplant. Six of the eight patients received OKT3 therapy without any apparent affect on clinical outcome. Compared to control group of patients (n = 28), 8 versus 2/28 had a positive cross-match with donor lymphocytes (P = NS), 1/8 versus 7/28 were ABO-non-identical (P = NS), 3/8 versus 10/21 had total MHC mismatches (P = NS) and 5/7 versus 6/16 had UW ischemic times above 10 h (P = NS). No patients had main hepatic artery thrombosis on angiography although four patients had evidence of intrahepatic microthrombi or arterial necrosis at autopsy. In all cases the histology showed massive haemorrhagic necrosis. Three cases had evidence of veno-occlusive lesions whilst foam cell arteriopathy was seen in two cases. Immunofluorescence was performed in three cases. In two cases there was evidence of immunoglobulin, complement and fibrin deposition in blood vessels. In conclusion, we describe an uncommon clinical syndrome occurring post liver transplant. This syndrome represents humorally mediated allograft rejection but there seems to be no relationship with tissue matching (antibody, ABO, MHC) or donor ischaemic times. If recognised earlier in the absence of multiorgan failure, urgent retransplantation seems to be the only effective therapy. PMID- 7888048 TI - Influence of liver transplantation and cyclosporin on bile secretion--an experimental study in the rat. AB - Bile secretion is reduced after liver transplantation. It has been suggested that this is due either to the effect of cyclosporin or to the damage to the liver graft during preservation and reperfusion. The aim of this study was to explore the influence of cyclosporin as well as of liver transplantation on bile secretion. Bile flow was studied in an experimental model in the rat. In syngeneic liver-transplanted animals, the bile flow was increased compared to the bile flow in the control group (1.29 +/- 0.09 ml/h vs 0.66 +/- 0.03 ml/h; P < 0.01), mainly due to an increased bile acid-independent flow (0.76 ml/h vs 0.50 ml/h; P < 0.01). The findings in the liver-transplanted rats contrasted with those in a group of nontransplanted animals treated with cyclosporin. Cyclosporin treatment resulted in a reduced bile acid-independent fraction (0.37 ml/h vs 0.50 ml/h, P < 0.05) of the bile flow, although no biochemical signs of hepatotoxicity were present. This reduction in the bile acid-independent fraction could, however, not be demonstrated when cyclosporin was given to a group of liver transplanted rats, although a reduced total bile flow was recorded in the 1st hour measurements. In contrast to previous studies, we found that the cyclosporin vehicle (Cremophor EL), when administered chronically, induced a higher bile flow than that in the control rats. This effect was not seen in the transplanted rats. Our findings in this experimental rat model indicate that cyclosporin will influence and reduce bile secretion and bile acid secretion even if no other signs of liver dysfunction are present. On the other hand, the preservation and reperfusion in this model resulted in an increased bile flow, while bile acid secretion remained constant. PMID- 7888049 TI - A pharmacokinetic comparison of cyclosporin oral solution and cyclosporin capsules in heart and lung transplant recipients. AB - Pharmacokinetic profiles were obtained for 16 heart or lung recipients following the administration of identical doses of cyclosporin as oral solution and capsules on consecutive days. A comparison of pharmacokinetic parameters (AUC, Cmax, Cmin and tmax) showed that there were no significant differences between the two formulations except for the tmax, which was significantly longer for the capsules. The mean variation in day-to-day trough levels produced by the two different forms was 25.6%. A retrospective study was carried out of consecutive cyclosporin levels in patients at steady state on oral solution. The mean variation in day-to-day trough levels was 32.3%. This was not significantly different from the variation in consecutive trough levels seen in the oral solution/capsule comparison. This study shows that cyclosporin capsules can be substituted for oral solution without causing acute changes in cyclosporin blood levels, and that the pharmacokinetics of the two formulations are similar. PMID- 7888050 TI - Orthotopic liver transplantation for hepatic-based metabolic disorders. AB - Between January 1989 and June 1993, a total of 470 liver transplantations were performed at King's College Hospital. Thirty-seven transplantations were performed in 34 patients with liver-based metabolic disease. There were 16 females and 18 males with a median age of 19 years (range 1 month to 62 years). There were 14 patients under 16 years of age. The indications for liver transplantation were Wilson's disease (n = 16), alpha 1-antitrypsin deficiency (n = 10), tyrosinaemia (n = 2), primary hyperoxaluria type 1 (PH1; n = 2), congenital haemochromatosis (n = 1), familial amyloidotic polyneuropathy (FAP; n = 1, familial hypercholesterolaemia) (n = 1) and Crigler-Najjar syndrome type I (CNS1; n = 1). These included two patients who received combined heart-liver grafts for familial hypercholesterolaemia and FAP, respectively. Two patients received combined liver-kidney transplants for PH1. There were four deaths: from sepsis (n = 2), acute hepatic vein obstruction in a left lateral segment graft (n = 1) and portal vein thrombosis with liver necrosis (n = 1). Three patients were retransplanted, one for chronic rejection and two for hepatic artery thrombosis, giving an overall graft survival of 81% and patient survival of 88% (30/34), at a mean follow-up of 34 months (range 10-64 months). PMID- 7888051 TI - Renal allograft rejection: the temporal relationship and predictive value of plasma TNF (alpha and beta), IFN-gamma and soluble ICAM-1. AB - Recently, close interactions have been described between the tumour necrosis factors alpha and beta (TNF-alpha and beta), interferon-gamma (INF-gamma) and intercellular adhesion molecule-1 (ICAM-1) in T-cell mediated immune activation. During the process of renal graft rejection, the properties of these cytokines to act as powerful stimulators of macrophages, to upregulate class II MHC expression and to stabilise cell-to-cell binding make them of great potential interest. The aim of the present study was to determine the plasma levels of each cytokine and soluble ICAM-1 in 16 renal allograft recipients. We examined plasmas of patients for the first 2 weeks after transplantation and correlated results with the clinical pattern of rejection. Our data suggest an immunopathologic involvement of TNF-alpha, TNF-beta and slCAM-1 in renal allograft rejection and showed that there was a significant elevation in plasma concentrations of these parameters 2 or 3 days prior to the diagnosis of clinical rejection. Rises in INF-gamma did not appear to be significant with regard to rejection as very high levels were found in patients showing no evidence of clinical rejection. PMID- 7888052 TI - Human natriuretic factor in cirrhotic patients undergoing orthotopic liver transplantation. AB - We measured the plasma levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation (OLT) in eight adult patients with cirrhosis and ascites. The aim of this study was to determine whether significant differences in ANF concentration may be detected during the individual phases of OLT and to correlate these changes with hemodynamics. In each patient a hemodynamic assessment was achieved using a Swan-Ganz fiber optic catheter for continuous monitoring of cardiac output (CO), systemic vascular resistance index (SVRI), right filling pressure as assessed by central venous pressure (CVP), and left filling pressure by means of pulmonary arterial wedge pressure (PAWP). During reperfusion a clear-cut increase in ANF values was observed (P < 0.05). Concurrently, an increase in CVP (P < 0.05) and a decrease in SVRI were observed without any significant increase in diuresis. These data suggest that ANF might play a role in the development of the reperfusion syndrome. PMID- 7888053 TI - Use of a single stent for double ureter support in transplantation. AB - A technique for draining both ureters of renal allografts with a single stent is described. The method simplifies the endoscopic removal of the stent. PMID- 7888054 TI - Herpes zoster-associated idiopathic thrombocytopenic purpura in a liver transplant recipient: a case report and overview. AB - Idiopathic (autoimmune) thrombocytopenic purpura has been previously reported as a rare complication in children and in a few adults following chickenpox. We report a case of varicella zoster virus-associated idiopathic thrombocytopenic purpura in an adult liver transplant recipient following dermatomal zoster. Idiopathic thrombocytopenic purpura developed 3 days after the onset of herpes zoster in our patient, with a nadir platelet count of 3000/mm3. The patient was treated with intravenous gamma globulin with recovery of thrombocytopenia after 3 weeks. Transplant clinicians need to be aware that this serious and potentially life-threatening complication may occur with herpes zoster in transplant recipients. PMID- 7888055 TI - Reduced size liver transplantation, split liver transplantation, and living related liver transplantation in relation to the donor organ shortage. AB - Because of the shortage of cadaveric donors, three techniques of partial liver grafting have been developed. These techniques are placed in perspective in relation to the organ shortage. Reduced size liver transplantation (RSLTx) is widely used and has results comparable to those from whole liver grafting. However, this technique, while benefitting pediatric patients, reduces the adult donor liver pool. It also makes inefficient use of an available adult donor liver. In split liver transplantation (SPLTx), the whole liver is used after bipartition for two recipients. The results are comparable to those of RSLTx. The problem with SPLTx is that it is a very demanding technique applied only in centers with extensive experience with liver resection and reduction. Living related liver transplantation (LRLTx) yields excellent results; however, it places an otherwise healthy person at risk. It is argued that instead of performing risky operations on healthy persons, the health authorities should take specific measures to alleviate the organ shortage. In the meantime, SPLTx should be developed further because of its optimal use of donor tissue. As for LRLTx, its excellent results and the present shortage of size-matched pediatric liver donors justify its use, at least for now. PMID- 7888056 TI - Is it right to develop living related liver transplantation? Do reduced and split livers not suffice to cover the needs? PMID- 7888057 TI - Portal stenosis in liver transplantation. Treatment by endoluminal prosthesis. PMID- 7888059 TI - Jerne and positive selection. PMID- 7888058 TI - Resuscitation of cardiac energy metabolism in the rabbit heart by brief hypothermic reperfusion after preservation studied by 31P NMR spectroscopy. AB - Rabbit hearts were subjected to 24-h cold ischaemic storage (at 0 degree-2 degrees C in melting ice) after initial flushing with either St Thomas' cardioplegic solution (STS) or modified lactobionate/raffinose solution (LR), and the status of phosphorylated energy metabolites was measured by 31phosphorus nuclear magnetic resonance (P NMR) spectroscopy. In both groups signals for ATP and phosphocreatine (PCr) were still detectable by 31P NMR after 24 h, and there was significantly more ATP in the LR group (P < 0.01). The hearts were then subjected to coronary reperfusion via an aortic cannula using the same storage solution (either STS or LR) at 6 degrees-8 degrees C, which was oxygenated. In both groups PCr recovered within 30 min of cold reperfusion, and by 60 min PCr was significantly higher in the LR group (P < 0.001). Also, levels of ATP were maintained at higher values during cold reperfusion i the LR group. These studies suggest two important points: (1) the general supply of phosphorylated high energy intermediates of hearts during cold ischaemic storage is better preserved using LR, and (2) brief cold reperfusion may be used to restore energy metabolism in hearts before re-implantation. PMID- 7888060 TI - Plant-derived metabolites with synergistic antioxidant activity. PMID- 7888061 TI - Gamma delta T cells, antigen recognition and intestinal immunity. PMID- 7888063 TI - New nomenclature for the Reth motif (or ARH1/TAM/ARAM/YXXL) PMID- 7888062 TI - Reply to Tauber. PMID- 7888064 TI - Nonself as a stressor--inflammation as a stress reaction. PMID- 7888065 TI - Inhibition of programmed eosinophil death: a key pathogenic event for eosinophilia? PMID- 7888066 TI - Immortalization of human T cells by Herpesvirus saimiri. PMID- 7888067 TI - Complement in human diseases: looking towards the 21st century. PMID- 7888068 TI - Post-thymectomy autoimmunity: abnormal T-cell homeostasis. AB - Thymectomy of 3-day-old mice induces organ-specific autoimmune disease, which is characterized by the presence of autoantibodies and T-cell infiltrates in the affected organs. Here, Adriana Bonomo and colleagues propose a new model for the pathogenesis of this syndrome, which integrates many of the homeostatic mechanisms of the immune system, including central and peripheral tolerance, T cell maturation and exportation from the thymus, as well as lymphocyte recirculation and homing. PMID- 7888069 TI - Human herpesvirus 6 in AIDS. AB - Multiple lines of clinical and experimental evidence suggest that human herpesvirus 6 (HHV-6) may act as an accelerating factor in the natural history of human immunodeficiency virus (HIV) infection. Although, in common with HIV, HHV-6 has a primary tropism for CD4+ T cells, its potential effects on the immune system are broader. For instance, HHV-6 can also infect and kill CD8+ T cells, natural killer cells and mononuclear phagocytes. Here, Paolo Lusso and Robert Gallo suggest that understanding the immunopathogenic role of HHV-6 in the course of HIV infection may shed new light on the complex mechanisms of disease progression in AIDS. PMID- 7888070 TI - CD30, Th2 cytokines and HIV infection: a complex and fascinating link. AB - CD30 is a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) receptor superfamily, and was originally described as a marker of Hodgkin's and Reed-Sternberg cells in Hodgkin's lymphoma. CD30 is preferentially expressed on CD4+ and CD8+ T-cell clones that produce T helper 2 (Th2)-type cytokines, and is also released in a soluble form by these cells. Elevated serum levels of soluble (s)CD30 have been found in some conditions in which a pathogenic role for Th2 cells has been suggested, such as atopy, Omenn's syndrome, systemic lupus erythematosus, as well as following infection with measles virus or human immuno deficiency virus (HIV). Here, Gianfranco Del Prete and colleagues suggest a complex and fascinating link between the expression and release of CD30, and the immunopathogenesis of HIV infection. PMID- 7888071 TI - A quantitative model of autoimmune disease and T-cell vaccination: does more mean less? AB - According to a simple mathematical model, the activated effector T cells that cause an autoimmune disorder can also cure the disease if administered in large doses. This prediction has been tested in the nonobese diabetic (NOD) mouse model and demonstrates that administration of intermediate doses of a diabetogenic T cell clone caused early hyperglycemia, whereas a higher dose cured the disease. As discussed here by Lee Segel and colleagues, the proposed application of T-cell vaccination to treat clinical disease obliges immunologists to consider the quantitative complexities of regulation. PMID- 7888072 TI - The structural requirements for complement activation by IgG: does it hinge on the hinge? AB - The flexibility of antibody molecules principally derives from the structure of the hinge region. It has generally been accepted that the flexibility of the IgG hinge is necessary for complement activation to occur; however, recent studies dispute this premise. As described here by Ole Henrik Brekke, Terje Michaelsen and Inger Sandlie, it now appears that the only requirement of the hinge region for complement activation is the presence of inter-heavy-chain disulfide bond(s). Furthermore, the structural basis for the differences between IgG subclasses with respect to effector functions appear to be located within the CH2 domain of the immunoglobulin molecule. PMID- 7888073 TI - The basis of autoimmunity: Part I. Mechanisms of aberrant self-recognition. AB - In this two-part series, Argyrios N. Theofilopoulos summarizes the current state of affairs in the field of autoimmunity. Part I integrates the collective mechanistic theories of autoimmune diseases. The most straightforward explanation to emerge with regard to organ-specific diseases is the concept that these are caused by inappropriate, yet conventional, immunological responses against self antigens for which tolerance has never been established. A similar mechanism may be operative in systemic autoimmunity, but other abnormalities such as defects in the apoptosis machinery may also be invoked. Part II will address the genetic contributions predisposing to autoimmune syndromes. PMID- 7888074 TI - A signaling pathway governing early thymocyte maturation. AB - Recent evidence supports the view that p56lck, a non-receptor protein tyrosine kinase, serves as the signaling element that 'senses' synthesis of a functional T cell receptor beta chain, thereby promoting thymocyte maturation. Here, Steven Anderson and Roger Perlmutter review current data, and outline the features of this developmental program. PMID- 7888075 TI - Current status of injectable oxygen carriers. AB - In this review the current status of what commonly are termed "blood substitutes" is discussed. The term blood substitute is a misnomer because the formulations under development at this time transport respiratory gases but do not perform the metabolic, regulatory, and protective functions of blood. Either hemoglobin or a perfluorochemical form the base to transport oxygen; the advantages and disadvantages of each base are discussed. The availability of a blood substitute in the U.S. will require approval by the Food and Drug Administration (FDA) and, by law, both its efficacy and safety must be demonstrated prior to approval. Showing efficacy of any blood substitute is complicated by the oxygen reserve and the compensatory mechanisms to acute blood loss in man. The challenge is to prove that the administration of these formulations offer clinical advantages compared with replacement of volume alone. Several efficacy models, the most attractive among them being perioperative hemodilution, should provide data that would bring these formulations into clinical practice. When hemoglobin is not within the favorable environment of the red cell, whether the hemoglobin is derived from expression vectors developed through recombinant biotechnology or from lysed human red cells, it acquires a left-shifted oxygen disassociation curve. Further, because the tetramer disassociates when injected intravenously and the resulting dimers are cleared rapidly from the circulation by the kidneys, intravascular dwell time is brief. Hemoglobins have been modified chemically and linked intramolecularly, intermolecularly, and to macromolecules to correct these problems. While these manipulations have normalized the p50 and extended the dwell time significantly, some toxicity problems remain unresolved. The binding of nitric oxide to hemoglobin preparations and the presumably resultant systemic and pulmonary hypertension observed in animals may be the most difficult to overcome, although the implications of these reactions in man is poorly understood. Perfluorochemicals (PFC) provide a fundamentally different and simpler approach to oxygen transport than hemoglobin formulations. Typically, the PFCs used are liquids composed of 8 to 10 carbon atoms that dissolve oxygen and obey Henry's law. Thus, the recipient's inspired oxygen and cardiac output assume importance. Because they are insoluble in water, PFCs are administered as emulsions, that is, as small droplets about 0.1 to 0.2 microns in diameter. In this respect, they are very similar to the lipid emulsions widely used for parenteral nutrition. Egg yolk phospholipid and poloxamers are most commonly used as emulsifiers. PFCs are not metabolized and are excreted unchanged by the lungs, following temporary storage by the monocyte-macrophage system (MMS).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7888076 TI - Amyloidosis. AB - The biochemistry of amyloidosis as it relates to clinical medicine and experimental pathology is presented. Amyloidoses are complex disorders in which normally soluble precursors undergo pathological conformational changes and polymerize as insoluble fibrils with the beta-pleated sheet conformation. Over the past 20 years, 16 biochemically diverse proteins have been identified as fibrillar constituents of amyloid deposits; in all cases the protein-protein interactions that result in amyloid fibril formation appear to be stabilized both by the structure and the microenvironment of the precursor protein. Either genetic predisposition or dysfunctions of the immune system favor amyloid fibril formation. In particular, macrophage function is a factor in the pathogenesis of many of the amyloidoses. The diagnosis of amyloidosis involves acquisition of a tissue biopsy, staining of the specimen with Congo red, and observation of classic green birefringence on polarization microscopy. The subdiagnosis of the systemic amyloidoses involves characterization of variant or monoclonal plasma amyloid precursor proteins in the context of clinical symptoms. Treatment is generally supportive, with the use of antiinflammatory therapy, dialysis, or transplantation and genetic counseling where indicated. PMID- 7888077 TI - Gene structure and regulation of expression of human glutathione S-transferases alpha. AB - Current knowledge on the structure of human alpha-class glutathione S-transferase (GST) genes and the regulation of their expression is reviewed. The alpha-class GST comprises several genes and pseudogenes localised in a tight cluster on chromosome 6. Although the human GSTA1 and GSTA2 genes have the same number of exons and introns as their rat and mouse counterparts, the sequences of the 5' flanking regions of the human alpha-class genes are significantly different from the rodents, suggesting different mechanisms of regulation between human and rodents. The expression of GST alpha is altered in a variety of tumors and several lines of evidence implicate the alpha-class GSTs in chemotherapeutic drug resistance. Finally, the induction of human GSTs by drugs or nutritional constituents would justify an interest for developing chemointervention strategies in populations highly exposed to carcinogens like aflatoxin B1 and polycyclic aromatic hydrocarbons. PMID- 7888078 TI - Comparison of properties of membrane bound versus soluble forms of human leukocytic elastase and cathepsin G. AB - Stimulation of human neutrophils with micromolar concentrations of N-formyl methionyl-leucyl-phenyl-alanine (fMLP) or 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA), results in their degranulation and/or lysis with a concomitant release of Human Leucocyte Elastase (HLE; EC 3.4.21.37), Cathepsin G (cat G; EC 3.4.21.20) and Myeloperoxidase (MPO; EC 1.11.1.7) into the surrounding medium, some of which re-bind in an active form to neutrophil plasma membranes or membrane fragments. Histones, when present in the medium, prevent this association indicating that it is largely charge dependent. Bound proteinases have an increased resistance to inhibition by protein proteinase inhibitors, while bound MPO retains its ability to oxidatively inactivate alpha-1-proteinase inhibitor (alpha-1-PI). The attachment of oxidases and proteinases to plasma membrane or its fragments may allow them to remain active in an environment replete with proteinase inhibitors and, therefore, may be responsible for neutrophil or neutrophil-debris mediated tissue damage. PMID- 7888079 TI - Glycosylated boar spermadhesin AWN-1 isoforms. Biological origin, structural characterization by lectin mapping, localization of O-glycosylation sites, and effect of glycosylation on ligand binding. AB - Spermadhesin AWN-1 is a 133-residues boar sperm surface lectin with capability to bind different ligands, e.g. glycoproteins from zona pellucida (ZP), soybean trypsin inhibitor and heparin, and is involved in capacitation and binding of spermatozoa to the homologous zona pellucida. Here, we report the characterization of N- and O-glycosylated isoforms of AWN-1. Non-glycosylated AWN 1 is present in seminal plasma and on epididymal and ejaculated spermatozoa whereas its N- and O-glycosylated isoforms are only secretory products of the seminal vesicles. Lectin mapping indicated the presence of the glycosylated AWN-1 isoform mixture of both fucosylated and non-fucosylated N-glycans, and of two different classes of O-linked carbohydrate chains. These N- and O-linked oligosaccharide chains are neither sialylated nor contain terminal Gal beta (1-4) GlcNAc sequences. Noteworthy, N- and O-glycosylation (either class) are mutually exclusive on the same protein molecule, indicating that each glycosylated AWN-1 molecule contains a single oligosaccharide chain. Peptide mapping was used to locate the N- and the O-glycosylation sites. Glycosylation of AWN-1 with either of the carbohydrate chain types greatly impaired the ability of the spermadhesin to bind biotinylated zona pellucida glycoproteins and soybean trypsin inhibitor, suggesting that the blocking effect may be due to steric hindrance of the ligand binding pocket. PMID- 7888080 TI - Short introns interrupting the Oct-2 POU domain may prevent recombination between POU family genes without interfering with potential POU domain 'shuffling' in evolution. AB - Transcription factors are often encoded by gene families that share the same type of DNA binding domain. The POU domain genes are one such paradigm. We compared the genomic DNA encoding the POU domain of the Oct-2 genes in human and mouse. In both species this domain is split into a cluster of four exons by short, highly diverged introns. We postulate that the main role of these introns is to prevent ectopic homologous recombination with other members of the POU gene family, with its potentially deleterious effects in somatic and germline cells. Such rapidly diverging introns may generally promote evolution by facilitating the maintenance of duplicated genes. The use of different codons for the same protein domain among members of a gene family may be a slower process that serves a similar purpose. Introns that split conserved domains such as the POU domain do not conform to the exon shuffling hypothesis originally put forward by W. Gilbert (1978). However, we note that the introns flanking the POU domain are in the same phase, i.e. interrupt codons in the same reading frame. Thus we propose that the entire POU domain, which is encoded by a tight cluster of exons, has been shuffled together during evolution as a functional unit, or 'shufflon'. PMID- 7888081 TI - A Kazal-type inhibitor of human mast cell tryptase: isolation from the medical leech Hirudo medicinalis, characterization, and sequence analysis. AB - Human tryptase, a tetrameric proteinase expressed by mast cells, is virtually unique among the serine proteinases as it is not inhibited by any proteinaceous inhibitor tested so far. We have now isolated, sequenced, and characterized an inhibitor of human tryptase from the medical leech Hirudo medicinalis. LDTI (Leech-Derived Tryptase Inhibitor) was purified to apparent homogeneity by cation exchange and affinity chromatography. Amino acid sequencing of the protein consisting of 46 residues (M(r) 4738) revealed a high degree of similarity to the non-classical Kazal-type inhibitors bdellin B-3 and rhodniin, inhibitors isolated from the medical leech and the insect Rhodnius prolixus, respectively. LDTI is a tight-binding and relatively specific inhibitor of human tryptase; it inhibits only trypsin (EC 3.4.21.4) and chymotrypsin (EC 3.4.21.1) with similar affinities. Inhibition studies using small chromogenic substrates revealed that LDTI inhibits the amidolytic activity of tryptase by approximately 50%, suggesting that most likely due to steric hindrance LDTI binds to and inhibits only 2 of 4 active sites of tryptase. LDTI appears useful as a prototype of inhibitors of human tryptase and as a pharmacological tool for the investigation of the role of tryptase in health and disease. PMID- 7888082 TI - Recombinant leech-derived tryptase inhibitor: construction, production, protein chemical characterization and inhibition of HIV-1 replication. AB - A synthetic gene coding for leech-derived tryptase inhibitor, form C (LDTI-C), was designed, cloned and expressed. The gene assembled via 6 oligonucleotides contains linker sequences, stop codons and internal restriction recognition sites for cloning, expression and cassette mutagenesis. Periplasmatic expression products could not be detected in Escherichia coli (E. coli), but strong expression was found using Saccharomyces cerevisiae (S. cerevisiae) ( > 10 mg/l culture broth) if a variant of pVT102U/alpha was used as vector. The secreted material was isolated after cross-flow filtration and purified by cation exchange chromatography. The recombinant material proved to be pure and homogeneous by electrophoretic and chromatographic analyses. Amino acid sequencing and molecular mass determination (4737.6 +/- 0.77 Da) by electrospray ionization mass spectrometry confirmed that rLDTI-C was processed correctly and that it is indistinguishable from LDTI-C. The far UV-CD (circular dichroism) spectrum of the recombinant inhibitor is typical for a small folded protein. rLDTI-C is inhibitorily fully active, its complexes with bovine trypsin and human mast cell tryptase display equilibrium dissociation constants which are nearly identical to those with the natural inhibitor. Remarkably, the inhibitor blocked replication of HIV-1 in HUT-78 cells at a concentration of 20 microM. PMID- 7888083 TI - Absence of activating mutations of the RAF1 protooncogene in human lung cancer. AB - Recently, the RAF protein has been demonstrated to be a direct effector of RAS protein in a RAS-mediated signal transduction pathway. Activations of the RAF1 gene by small mutations, such as point mutations in the kinase domain and a tetrapeptide insertion into conserved region 2, have been suggested from analyses of chemically induced lung cancers in mice and by site-directed mutagenesis. We investigated the presence of small mutations of the RAF1 gene in human lung carcinomas, especially in those not carrying the mutated RAS gene, expecting that aberrations of the RAF1 gene might play a role complementary to RAS gene mutations in tumorigenesis. Single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction products of DNA samples from 140 patients revealed no tumor specific mutations of the RAF1 gene in any of these specimens. This result suggests that mutations of the RAF1 gene are not involved in tumorigenesis in human lung. PMID- 7888084 TI - Two-chain bacteriorhodopsin synthesized by Schizosaccharomyces pombe. AB - Bacteriorhodopsin (BR), the light-driven proton pump of Halobacterium salinarium purple membrane, was produced in functional form as a two-chain protein by simultaneous expression in the fission yeast Schizosaccharomyces pombe of two separate structural genes, one coding for an aminoterminal BR fragment encompassing the first two transmembrane helices of BR, the other coding for the remainder of the protein. The fragments assemble spontaneously in vivo to yield functional BR which can be purified by immobilized metal ion affinity chromatography. PMID- 7888086 TI - Development of an anti-A beta monoclonal antibody for in vivo imaging of amyloid angiopathy in Alzheimer's disease. AB - We evaluated the efficacy of murine monoclonal antibodies (MAbs) targeted to the A beta amyloid of Alzheimer's disease for development of procedures for the in vivo identification of amyloid angiopathy (AA). MAbs to A beta were prepared and screened for effectiveness in visualizing AA and neuritic plaques in postmortem AD brain sections. They were assessed again after enzymatic cleavage to produce Fab fragments and after labeling with technetium-99m (99mTc) using a diamide dimercaptide ligand system. Modified and radiolabeled Fab fragments retained activity and specificity toward amyloid-laden blood vessels and neuritic plaques. A highly specific murine MAb, 10H3, was identified and characterized that fulfills criteria necessary for the development of an in vivo diagnostic imaging agent. Toxicity studies in rats showed the MAb to be safe. Biodistribution studies in mice demonstrated desirable properties for use as an imaging agent. Expansion and adaptation of these strategies may provide the methods and materials for the noninvasive analysis of AA in living patients, and permit assessment of the contribution of AA to the clinical and pathological features of AD. PMID- 7888087 TI - Therapy for Alzheimer's disease. Symptomatic or neuroprotective? AB - Therapeutic strategies aimed to treat Alzheimer's disease (AD) may either produce an attenuation of symptoms or slowdown deterioration by attenuating progression of the disease. Presently, cholinesterase inhibitors (ChEI) have shown the most promising therapeutic effects. The best documented clinical efficacy of ChEI are studies of THA (tacrine, tetrahydroaminoacridine). The results of five recent studies in a total of 1,242 patients are discussed. Based on differences from placebo in scoring, a gain of 2-12 (MMSE) or 5-6 (ADAS) in deterioration can be seen for a THA treatment of 2-3 mo duration. This suggests that if treatment with THA will be extended to a longer period, the drug effect may not be only a symptomatic improvement but also a slowdown of disease course. A similarity of THA's effect in AD with L-deprenyl effects in Parkinson's is suggested. PMID- 7888085 TI - Possible factors in the etiology of Alzheimer's disease. AB - Inherited cases of Alzheimer's disease (AD) comprise only a very small proportion of the total. The remainder are of unknown etiopathogenesis, but they are very probably multifactorial in origin. This article describes studies on four possible factors: aluminum; viruses--in particular, herpes simplex type I virus (HSV1); defective DNA repair; and head trauma. Specific problems associated with aluminum, such as inadvertent contamination and its insolubility, have led to some controversy over its usage. Nonetheless, the effects of aluminum on animals and neuronal cells in culture have been studied intensively. Changes in protein structure and location in the cell are described, including the finding in this laboratory of a change in tau resembling that in AD neurofibrillary tangles, and also the lack of appreciable binding of aluminum to DNA. As for HSV1, there has previously been uncertainty about whether HSV1 DNA is present in human brain. Work in this laboratory using polymerase chain reaction has shown that HSV1 DNA is present in many normal aged brains and AD brains, but is absent in brains from younger people. Studies on DNA damage and repair in AD and normal cells are described, and finally, the possible involvement of head trauma is discussed. PMID- 7888088 TI - Mechanism of neurofibrillary degeneration in Alzheimer's disease. AB - Neurofibrillary degeneration associated with the formation of intraneuronal neurofibrillary tangles of paired helical filaments (PHF) and 2.1 nm tau filaments is one of the most characteristic brain lesions of Alzheimer's disease. The major polypeptides of PHF are the microtubule associated protein tau. tau in PHF is present in abnormally phosphorylated forms. In addition to the PHF, the abnormal tau is present in soluble non-PHF form in the Alzheimer's disease brain. The level of tau in Alzheimer's disease neocortex is severalfold higher than in aged control brain, and this increase is in the form of the abnormally phosphorylated protein. The abnormally phosphorylated tau does not promote the assembly of tubulin into microtubules in vitro, and it inhibits the normal tau stimulated microtubule assembly. After in vitro dephosphorylation both PHF and non-PHF abnormal tau stimulate the assembly of tubulin into microtubules. The activities of phosphoseryl/phosphothreonyl protein phosphatase 2A and nonreceptor phosphotyrosyl phosphatase(s) are decreased in AD brain. It is suggested that 1. A defect(s) in the protein phosphorylation/dephosphorylation system is one of the early events in the neurofibrillary pathology in AD; 2. A decrease in protein phosphatase activities, at least in part, allows the hyperphosphorylation of tau; and 3. Abnormal phosphorylation and polymerization of tau into PHF most probably lead to a breakdown of the microtubule system and consequently to neuronal degeneration. PMID- 7888089 TI - Biochemistry of Parkinson's disease with special reference to the dopaminergic systems. AB - The cardinal neurochemical abnormality in Parkinson's disease is the decreased dopamine content in the striatum, resulting from the loss of dopaminergic neurons in the mesencephalon. Precise analysis of the dopaminergic neurons in the midbrain demonstrates, however, that this cell loss is not uniform. Some dopaminergic cell groups are more vulnerable than others. The degree of cell loss is severe in the substantia nigra pars compacta, intermediate in the ventral tegmental area and cell group A8, but nonexistent in the central gray substance. This heterogeneity provides a good paradigm for analyzing the factors implicated in this differential vulnerability. So far, the neurons that degenerate have been shown to contain neuromelanin, high amounts of iron, and no calbindin28K, and to be poorly protected against oxidative stress. By contrast, the neurons that survive in Parkinson's disease are free of neuromelanin, calbindinD28-positive, contain low amounts of iron, and are better protected against oxidative stress. The analysis of the pattern of cell loss in Parkinson's disease may thus bring new clues as to the mechanism of nerve cell death in Parkinson's disease. PMID- 7888090 TI - Physiological mechanisms and movement analysis in Parkinson's disease. AB - We present new ideas about motor control in the human central nervous system and about pathophysiological mechanisms of Parkinson's disease, and we describe the Posturo-Locomotion-Manual (PLM) method, which is a new technique utilizing optoelectronic camera recording for objective, fully quantitative, and standardized assessment of human motor performance. In the PLM test, recordings of body movements are made during a simple motor task, where the subject repeatedly moves a small object from its starting position on the floor to a shelf located at chin height a few steps forward. The duration of the postural (raising up), locomotor and the goal-directed manual phase of the forward directed body movement is automatically calculated by a small computer as well as the degree of coordination (simultaneity) of these phases. The technique has high resolution and has been used for clinical assessment of motor performance, drug testing, and so on, in neurological and geriatric practice. PMID- 7888091 TI - Substantia nigra degeneration and tyrosine hydroxylase depletion caused by excess S-adenosylmethionine in the rat brain. Support for an excess methylation hypothesis for parkinsonism. AB - The major symptoms of Parkinson's disease (PD) are tremors, hypokinesia, rigidity, and abnormal posture, caused by degeneration of dopamine (DA) neurons in the substantia nigra (SN) and deficiency of DA in the neostriatal dopaminergic terminals. Norepinephrine, serotonin, and melanin pigments are also decreased and cholinergic activity is increased. The cause of PD is unknown. Increased methylation reactions may play a role in the etiology of PD, because it has been observed recently that the CNS administration of S-adenosyl-L-methionine (SAM), the methyl donor, caused tremors, hypokinesia, and rigidity; symptoms that resemble those that occur in PD. Furthermore, many of the biochemical changes seen in PD resemble changes that could occur if SAM-dependent methylation reactions are increased in the brain, and interestingly, L-DOPA, the most effective drug used to treat PD, reacts avidly with SAM. So methylation may be important in PD; an idea that is of particular interest because methylation reactions increase in aging, the symptoms of PD are strikingly similar to the neurological and functional changes seen in advanced aging, and PD is age related. For methylation to be regarded as important in PD it means that, along with its biochemical reactions and behavioral effects, increased methylation should also cause specific neuronal degeneration. To know this, the effects of an increase in methylation in the brain were studied by injecting SAM into the lateral ventricle of rats. The injection of SAM caused neuronal degeneration, noted by a loss of neurons, gliosis, and increased silver reactive fibers in the SN. The degeneration was accompanied with a decrease in SN tyrosine hydroxylase (TH) immunoreactivity, and degeneration of TH-containing fibers. At the injection site in the lateral ventricle it appears that SAM caused a weakening or dissolution of the intercellular substances; observed as a disruption of the ependymal cell layer and the adjacent caudate tissues. SAM may also cause brain atrophy; evidenced by the dilation of the cerebral ventricle. Most of the SAM induced anatomical changes that were observed in the rat model are similar to the changes that occur in PD, which further support a role of SAM-dependent increased methylation in PD. PMID- 7888092 TI - The molecular genetics of Alzheimer's disease. AB - The major pathological characteristic of Alzheimer's disease (AD) is the abnormal deposition of beta-amyloid peptide (A beta) in the brain. In some early onset cases, the disease develops because of mutations in the gene coding for beta amyloid precursor protein (beta APP). However, the majority of AD families in the early onset subgroup are linked to a locus on chromosome 14. The genetic analysis and age of onset correlates of both the beta APP gene and the chromosome 14 locus are discussed. We speculate on the mechanisms by which the beta APP mutations cause the disease and discuss recent advances in beta APP processing that may be relevant to the pathogenesis of the late-onset (common) form of the disease. In addition, we review the association of the APOE locus with late-onset familial and nonfamilial disease. Further work is required to establish the effects of this locus on disease occurrence, age of onset, and progression. The molecular pathology of ApoE in relation to AD development and the identification of the chromosome 14 gene will greatly contribute to a general pathogenic model of AD, and will clarify the role of beta APP and its derivatives. PMID- 7888093 TI - Evolution of nerve fiber degeneration in the striatum in the MPTP-treated squirrel monkey. AB - We have examined the ultrastructure of the striatum in squirrel monkeys 1-5 d after a single sc injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 2.5 mg/kg. One untreated monkey served as control. We expected to find a dense degeneration of the dopamine terminals, but found instead that the main abnormality consisted of a focal vacuolation of the tissue, perhaps related to the striosome/matrix mosaic of the neostriatum. The vacuolation involved not only terminals, but also other parts of the neuropil. The severity of the destructive process increased from d 1-5. We conclude that MPP+, the toxic metabolite of MPTP, may gain access to the neuropil, either before or after its active uptake into and subsequent destruction of the dopamine terminals. In the present study, abnormalities were observed simultaneously in the striatum and substantia nigra as early as 24 h after MPTP administration. It is, however, possible that the time-course might differ between the two locations with even shorter time intervals or changes in dosage of MPTP. PMID- 7888094 TI - Neurocircuitry of the basal ganglia studied by monitoring neurotransmitter release. Effects of intracerebral and perinatal asphyctic lesions. AB - The neurocircuitries of the basal ganglia are studied with in vivo microdialysis, with special consideration to dopamine transmission and its interaction with other neurotransmitter systems. The aim is to develop experimental models to study the pathophysiology and therapy of neurodegenerative disorders of the basal ganglia, as well as to develop models to study the short- and long-term consequences of perinatal asphyctic lesions. A main goal of these studies is to find and to characterize new treatments for these disorders. PMID- 7888095 TI - The weaver mutant mouse as a model of nigrostriatal dysfunction. AB - The weaver mutant mouse has a genetic defect that results in the loss of dopamine neurons in the nigrostriatal pathway. Striatal tyrosine hydroxylase and dopamine content are reduced by 60-70%, and dopamine uptake is reduced by as much as 95%. Deficits in all three of these striatal dopamine markers are seen as early as postnatal d 3. The striatal dopamine systems in the weaver apparently have the ability to compensate for this dopamine deficit. Thus, in the weaver, in vitro resting release, as well as amphetamine-evoked fractional release of endogenous dopamine are increased. An additional change seen in the weaver striatum is an elevated serotonin content. These alterations may play an adaptive role in attempting to compensate for the dopamine loss. In summary, the weaver mutant mouse has dramatic deficits in the nigrostriatal pathway, but also seems to develop certain adaptive mechanisms in dopaminergic and other transmitter systems that may compensate functionally for the dopamine deficit. Thus, the weaver mouse provides a unique animal model for studying naturally induced neuronal degeneration that complements those models using surgical and pharmacological protocols. PMID- 7888096 TI - Catecholamine-containing biodegradable microsphere implants as a novel approach in the treatment of CNS neurodegenerative disease. A review of experimental studies in DA-lesioned rats. AB - Biodegradable controlled-release microsphere systems made with the biocompatible biodegradable polyester excipient poly(DL-lactide-co-glycolide) constitute an exciting new technology for drug delivery to the central nervous system (CNS). Implantable controlled-release microspheres containing dopamine (DA) or norepinephrine (NE) provide a novel means to compare DA- or NE -induced restitution of function in unilateral 6-hydroxydopamine lesioned rats. A suspension of 3 microL of DA- or NE-containing microspheres or empty microspheres was implanted in 2 sites of the DA denervated striatum of rats previously unilaterally lesioned with 6-hydroxydopamine. Contralateral-rotational behavior induced by apomorphine was used as an index of lesion success and, following implantation of the microspheres, also as an index of functional recovery. Interestingly, both DA- and NE-microsphere-implanted rats displayed a 30-50% reduction in the number of apomorphine-induced rotations up to 8 wk postimplantation. Rats implanted with empty microspheres did not demonstrate significant changes in contralateral rotational behavior. Behavioral studies following implantation of a mixture of DA and NE microspheres revealed an 80% decrease in the number of apomorphine induced rotations up to 4 wk. On conclusion of the studies, immunocytochemical examination revealed growth of DA and tyrosine hydroxylase immunoreactive fibers in the striatum of DA and NE microsphere implanted rats. Functional behavior appeared to correlate with the degree of fiber growth. Preliminary electron microscopic studies showed signs of axonal sprouting in the vicinity of the implanted microspheres. No growth was noted in rats implanted with empty microspheres. This report reviews the abilities of both microencapsulated NE and DA to assure functional recovery and to promote DA fiber (re)growth in parkinsonian rats. This novel means to deliver these substances to the central nervous system could be of therapeutic usefulness in Parkinson's disease. PMID- 7888098 TI - Growth factor receptors in amyotrophic lateral sclerosis. AB - The regional distribution of nerve growth factor (NGF) and insulin-like growth factor-1 (IGF-1) receptors in human spinal cords from controls and amyotrophic lateral sclerosis (ALS) patients was studied by quantitative autoradiography. High-affinity nerve growth factor receptors were found to be distributed to a similar extent within the various segments of the human spinal cord and predominantly within the substantia gelatinosa of the dorsal horn, whereas no significant binding could be detected in the motor-neuron areas. A similar pattern of binding was obtained in the ALS spinal cords. Moreover, no reexpression of NGF receptors could be demonstrated in the motor-neuron areas of ALS spinal cords. When comparing 125I-IGF-1 binding in the different spinal levels of normal spinal cord, the same distribution pattern was found in which the binding was highest in the central canal > dorsal horn > ventral horn > white matter. In the ALS cases, although a general upregulation of IGF-1 receptors was observed throughout the spinal cord, significant increases were observed in the cervical and sacral segments compared to controls. The cartography of IGF-1 receptors in the normal spinal cord as well as the change of these receptors in diseased spinal cord may be of importance in future treatment strategies of ALS. PMID- 7888097 TI - Behavioral assessment of the ability of intracerebral embryonic neural tissue grafts to ameliorate the effects of brain damage in marmosets. AB - The transplantation of neuronal tissue into the brains of patients with Parkinson's disease is already being assessed as an experimental treatment for the symptoms of this disease, and the possibility of using similar graft tissue to ameliorate the symptoms of other neurodegenerative diseases is being considered. In this context, a small number of transplant experiments have been carried out in monkeys with lesions of the central dopamine and cholinergic systems. These experiments make it possible to determine the optimum methods of transplantation in an animal whose brain is structurally more closely related to the human than that of the rat and to assess the behavioral consequences of transplantation on symptoms that either resemble very closely the symptoms seen in patients, or are of a complex cognitive nature and are therefore more difficult to measure in the rat. It is intended that these experiments will contribute to the development of better treatments for the neurodegenerative diseases, either by the use of transplantation as a clinical treatment, or by contributing to a better understanding of the mechanisms that normally maintain neuronal function and that fail in these diseases. PMID- 7888099 TI - Proteoglycans and other basement membrane proteins in amyloidoses. PMID- 7888100 TI - Promoting and directing axon outgrowth. AB - Establishment of appropriate neuronal connections during development and regeneration requires the extension of processes that must then grow in the correct direction, find and recognize their targets, and make synapses with them. During development, embryonic neurons gradually establish central and peripheral connections in an evolving cellular environment in which neurotrophic factors are provided by supporting and target cells that promote neuronal survival, differentiation, and process outgrowth. Some cells also release neurotropic factors that direct the outgrowth of neuronal processes toward their targets. Following development the neurotrophic requirements of some adult neurons change so that, although they respond to neurotrophic factors, they no longer require exogenous neurotrophins to survive or to extend processes. Within the central nervous system (CNS), the ability of neurons to extend processes is eventually lost because of a change in their cellular environment from outgrowth permissive to inhibitory. Thus, neuronal connections that are lost in the adult CNS are rarely reestablished. In contrast, the environment of the adult peripheral nervous system fosters process outgrowth and synapse formation. This article discusses the neurotrophic requirements of embryonic and adult neurons, as well as the importance of neurotropic factors in directing the outgrowth of regenerating adult axons. PMID- 7888101 TI - Morphological aberrations in therapy-resistant partial epilepsy (TRPE). Confocal laser scanning and 3D reconstructions of Lucifer Yellow injected atypical pyramidal neurons in epileptic human cortex. AB - Epileptic temporal and parietal cortices, removed from 6 patients with therapy resistant (intractable) partial epilepsy (TRPE) during neurosurgery, were studied. Neurons (40-50 in each slice) in laminae I-VI and white matter were injected with Lucifer Yellow (LY). Samples were examined in a confocal laser scanning microscope (BioRad [Richmond, CA] MRC 600), and individual cells were scanned at 0.1-2 microns incremental levels. 2D maximal linear projection was used for overview. Frames (50-60) of scanned neurons were transformed into 3D volumes, using VoxelView software on a Silicone Graphics workstation, and rotated. All samples contained pyramidal neurons with duplicated apical dendrites, additional basal dendrites, or were misplaced in a horizontal position in the white matter. Rarely were such cells observed in normal cases. The relation between the observations and the disease is discussed. The attempt to simultaneously apply immunofluorescence was successful concerning synaptic vesicle antigens. This approach will be used for a detailed study of the synaptology of this disease. PMID- 7888102 TI - Proteoglycans and the acute-phase response in Alzheimer's disease brain. AB - Alzheimer's disease is a dementing disorder affecting increasingly large numbers of individuals in the aging population. The characteristic neuropathologic changes of Alzheimer's disease are the deposition of extracellular amyloid plaques, neurons containing neurofibrillary tangles, and neuronal cell loss. The A4 amyloid peptide is the major constituent of senile plaques. In addition to the A4 peptide, senile plaques contain a variety of molecular species, including proteoglycans and inflammatory components. The presence of proteoglycans in the amyloid deposits of Alzheimer's disease and of systemic amyloidoses suggests that these molecules play an active role in the pathogenesis of amyloidosis. However, the molecular mechanisms that lead to the codeposition of amyloid peptide with proteoglycans is still unknown. Recent evidence suggests that the metabolism of proteoglycans is altered in Alzheimer's disease patients. The acute-phase response observed in the brain of patients affected by Alzheimer's disease may be responsible for this effect. In this article, we discuss the role of proteoglycans in Alzheimer's disease, and the possible interactions between factors involved in brain inflammatory mechanisms and proteoglycans in the pathogenesis of Alzheimer's disease. PMID- 7888103 TI - Altered GABAergic and glutamatergic transmission in audiogenic seizure susceptible mice. AB - The C57BL/10 SPS/sps mouse mutant are audiogenic seizure-susceptible. The enzymatic activities of glutamate decarboxylase (GAD), GABA aminotransferase (GABA-T), alanine aminotransferase (ALA-T), aspartate aminotransferase (ASP-T), and glutamate dehydrogenase (GDH) of whole brain supernatant are significantly reduced in these epileptic mice. GABA uptake is decreased in cortex, midbrain, and pons medulla. Previous studies showed the presence of two sodium-dependent GLU uptake systems in normal (SPS/SP) mice. Glutamate Umax by System 1 is significantly decreased in these mice, whereas the Umax value for System 2 is significantly increased in the epileptic mice. PMID- 7888104 TI - Excitotoxicity. Experimental correlates to human epilepsy. AB - Neurochemical observations on cortical biopsies form 48 patients under surgical treatment for pharmacoresistant partial epilepsy showed a 70-80% increase in glutamate concentration when expressed in relation to neuron specific enolase. Intraperitoneal administration of one of its receptor agonists, kainic acid (KA), to the rat led to increased epileptogenic activity of the limbic type in a dose dependent fashion. The KA injection also led to a neuronal cell death and a gliosis, closely correlated to the extent of seizure activity. In biopsies from human epileptogenic cortex, the concentration of neuron specific enolase correlated inversely to that of glial fibrillary acidic protein, a marker for astrocytic glial cells. Stimulation of the KA receptor decreased the extent of phosphorylation of the largest subunit of neurofilaments (NF-H) that have consequences for structural stability and axonal transport. Phosphorylated NF-H decreased also in human epileptic cortex, indicating either an overactivity of excitatory neurotransmitters or a loss of axonal compartments. PMID- 7888105 TI - Microvascular pathology and vascular basement membrane components in Alzheimer's disease. AB - Several factors have highlighted the vasculature in Alzheimer's disease (AD): Cerebral amyloid angiopathy (CAA) is common, amyloid fibrils emanate from the vascular basement membrane (VBM), and similar forms of beta-amyloid are found in vascular and parenchymal amyloid accumulations. The present article discusses the presence of microvascular pathology in AD. Microangiopathy, in addition to neurofibrillary tangles, senile plaques, and CAA, is a common pathologic hallmark of AD. VBM components are associated with amyloid plaques, and nonamyloidotic alterations of the VBM occur in brain regions susceptible to AD lesions. Also, intra-VBM perivascular cells (traditionally called pericytes), a subset of which share the immunophenotype of microglia and other mononuclear phagocytic system (MPS) cells, have been implicated in vascular alterations and cerebrovascular amyloid deposition. Perivascular and parenchymal MPS cells have access to several sources of the beta-amyloid protein precursor, including platelets, circulating white cells, and neurons. MPS cells would thus be ideally situated to uptake and process the precursor, and deposit beta-amyloid in a fashion analogous to that seen in other forms of systemic and cerebral amyloidoses. PMID- 7888106 TI - Alzheimer's disease cerebrospinal fluid antibodies display selectivity for microglia. Investigations with cell cultures and human cortical biopsies. AB - Previous investigations demonstrated that the cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients contains antibodies that recognize specific neuronal populations in the adult rat central nervous system (CNS). These findings suggest a pathogenic role for immunological aberrations in this disorder. To determine if antibodies may provide a means to differentially diagnose the dementias, CSF from a diversified dementia population was screened against the developing rat CNS and a cell culture system. Markings produced by AD CSF were distinctly different from those of vascular dementias (VAD) against the developing rat CNS. More importantly, some AD CSF recognized amoeboid microglia. The recognition of amoeboid microglia by antibodies in AD CSF is particularly interesting since these cells proliferate in response to nervous system disease and also engulf debris. A cell culture technique was developed to allow the rapid screening of CSF antibodies. Patient CSF produced five different types of markings in the cell culture: microglia, glioblasts, fibers, nonspecific, or negative. Correlations with these structures and the diagnosis of four different dementia populations revealed that, in comparison to the other groups, AD CSF displayed remarkable selectivity toward microglial cells. Cortical biopsies from patients suspected to have AD were incubated with the patient's own CSF and that of confirmed AD patients. Both CSF samples recognized microglial cells in the patient's cortical biopsy. The same CSF samples incubated against normal human cortical autopsy or a biopsy from a 3-mo-old child displayed negative immunoreactivity. These three approaches suggest that the presence of CSF microglial antibodies may be a means to distinguish AD patients from other dementias. The results add further support to the widely growing concept that inflammation and similar immune mechanisms may contribute to AD pathogenesis. PMID- 7888107 TI - Heterogeneity of Alzheimer's disease. An interpretive review. PMID- 7888108 TI - Antibodies to different isoforms of the heavy neurofilament protein (NF-H) in normal aging and Alzheimer's disease. AB - Sera of normal controls and of patients with neurological diseases contain antineurofilament antibodies. Recent studies suggest that biochemically and immunologically distinct subclasses of neurofilaments occur in different types of neurons. Alzheimer's disease (AD), the major cause of dementia, is associated with a marked degeneration of brain cholinergic neurons. In the present work we characterized the repertoire and age dependence of antineurofilament antibodies in normal sera and examined whether the degeneration of cholinergic neurons in AD is associated with serum antibodies directed specifically against the neurofilaments of mammalian cholinergic neurons. This was performed by immunoblot assays utilizing neurofilaments from the purely cholinergic bovine ventral root neurons and from the chemically heterogeneous bovine dorsal root neurons. Antibodies to the heavy neurofilament protein NF-H were detected in normal control sera. Their levels were significantly higher in older (aged 70-79) than in younger (aged 40-59) subjects. These antibodies bound similarly to bovine ventral root and dorsal root NF-H and their NF-H specificity was unchanged during aging. In contrast, the levels of IgG in AD sera that are directed against ventral root cholinergic NF-H were higher than those directed against the chemically heterogeneous dorsal root NF-H. Immunoblot experiments utilizing dephosphorylated ventral root and dorsal root NF-H and chymotryptic fragments of these molecules revealed that AD sera contain a repertoire of antimamalian NF-H IgG. A subpopulation of these antibodies binds to phosphorylated epitopes that are specifically enriched in ventral root cholinergic NF-H and that are located on the carboxy terminal domain of this molecule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888110 TI - Consequences of prolonged inhalation of ozone on F344/N rats: collaborative studies. Part VII: Effects on the nasal mucociliary apparatus. AB - Besides the centriacinar region of the lung, the nose is a principal target for ozone toxicity. Acute exposures to concentrations of ozone in ambient air induce secretory cell metaplasia in the nasal transitional epithelium of rats. This study examined the effects of chronic ozone exposure on the structure and function of the nasal mucociliary apparatus of the rat. Male and female F344/N rats were exposed to ozone concentrations of 0.0 (controls), 0.12, 0.5, or 1.0 parts per million (ppm), six hours per day, five days per week, for 20 months. All rats were killed seven or eight days after the end of the exposure. Immediately after death, mucous flow rates throughout the nasal passages were determined using in vitro video motion analysis. Following assessment of mucociliary function, the nasal tissues were processed for light microscopy and stained with Alcian blue (pH 2.5)/periodic acid-Schiff to detect intraepithelial mucus. Image analysis was used to quantitate the amount of mucus within the nasal transitional epithelium. In rats exposed to 0.5 or 1.0 ppm ozone, mucous flow rates were markedly slower over the lateral wall and turbinates of the proximal third of the nasal airways than they were in rats exposed to 0.0 or 0.12 ppm ozone. These intranasal regions in the rats exposed to 0.5 or 1.0 ppm ozone contained marked mucous cell metaplasia and 25 to 300 times more mucus in nasal transitional epithelium than was found in control rats. In addition, male and female rats exposed to 0.5 or 1.0 ppm ozone had marked epithelial hyperplasia in nasal transitional epithelium, increases in eosinophilic globules in the surface epithelium lining the distal nasal airways, and a mild to moderate inflammatory cell influx in the nasal mucosa in the proximal and middle nasal passages. Male rats also had conspicuous bony atrophy in maxilloturbinates and nasoturbinates. There were no significant decreases between the mucous flow rates of rats exposed to 0.12 ppm ozone and those of control rats. There were, however, mild increases in various flow rates in some areas of the nasal airways in rats exposed to 0.12 ppm ozone compared with control rats. No significant morphologic alterations were evident in the rats exposed to 0.0 or 0.12 ppm ozone. The results of this study indicate that rats chronically exposed to 0.5 or 1.0 ppm ozone have significant alterations in the function and structure of the nasal mucociliary apparatus. Though there was a mild increase in mucous flow rates in a few nasal regions of some rats exposed to 0.12 ppm ozone, this functional change was interpreted as a physiologic, rather than a pathologic, response to ozone at this relatively low concentration. PMID- 7888109 TI - PD 142676 (CI 1002), a novel anticholinesterase and muscarinic antagonist. AB - Inhibition of brain acetylcholinesterase (AChE) can provide relief from the cognitive loss associated with Alzheimer's disease (AD). However, unwanted peripheral side effects often limit the usefulness of the available anticholinesterases. Recently, we identified a dihydroquinazoline compound, PD 142676 (CI 1002) that is a potent anticholinesterase and a functional muscarinic antagonist at higher concentrations. Peripherally, PD 142676, unlike other anticholinesterases, inhibits gastrointestinal motility in rats, an effect consistent with its muscarinic antagonist properties. Centrally, the compound acts as a cholinomimetic. In rats, PD 142676 decreases core body temperature. It also increases neocortical arousal, as measured by quantitative electroencephalography, and cortical acetylcholine levels, measured by in vivo microdialysis. The compound improves the performance of C57/B10j mice in a water maze task and of aged rhesus monkeys in a delayed match-to-sample task involving short-term memory. The combined effect of AChE inhibition and muscarinic antagonism distinguishes PD 142676 from other anticholinesterases, and may be useful in treating the cognitive dysfunction of AD and produce fewer peripheral side effects. PMID- 7888111 TI - Diagnostic strategies in HIV-infected patients with diarrhea. PMID- 7888112 TI - Identification of an env G subtype and heterogeneity of HIV-1 strains in the Russian Federation and Belarus. AB - OBJECTIVE: To identify HIV-1 envelope sequence subtypes in infected individuals from the Russian Federation and Belarus. PATIENTS: A cohort of children infected after exposure to non-sterile needles during the 1988-1989 HIV-1 epidemic in southern Russia (n = 20) and HIV-1-seropositive individuals from Russia (n = 1) and Belarus (n = 7) infected via sexual transmission. METHODS: DNA samples derived from peripheral blood mononuclear cells were analysed for their HIV-1 genotypes by the heteroduplex mobility assay (HMA). The 1.3 kilobase-pair env gene fragments encoding a portion of gp120 were amplified by nested polymerase chain reaction, cloned and sequenced. The env sequences derived from these patients were aligned and phylogenetic neighbour-joining and maximum parsimony derived trees generated. RESULTS: The env sequences derived from eight individuals infected in Russia and Belarus belong to subtype A (one), B (four), C (two), and D (one). Sequences derived from children, infected during parenteral manipulations in southern Russia, and one mother were closely related, but highly divergent, as a group, from all prototypic strains (genetic divergence, 17.2 22.9%). However, they clustered together with env sequences of the V1525 and LBV21-7 isolates from Gabon, recently described to be members of a new HIV-1 env subtype G. CONCLUSION: Extensive heterogeneity of HIV-1 subtypes was evident in the Russian Federation and Belarus. Our data also support the existence of an HIV 1 env genetic subtype G, and such isolates are now apparently present on both the African and European continents. These variants were identified through V3 peptide enzyme-linked immunosorbent assay screening and subsequent HMA analysis. The combination of these techniques represents a model for screening HIV variants within a large population. PMID- 7888114 TI - Distinct alterations in the distribution of CD45RO+ T-cell subsets in HIV-2 compared with HIV-1 infection. AB - OBJECTIVE AND DESIGN: Some clinical studies indicate that disease progression in HIV-2-infected subjects may be slower than in HIV-1. We investigated whether there were differences in the distribution of CD45RO+ (memory) and CD45RA+ (naive) T-cell subsets between HIV-1 and HIV-2 infection. METHODS: Analysis of lymphocyte subsets was performed by flow cytometry in peripheral blood mononuclear cells from healthy controls, HIV-1-(n = 49) and HIV-2-infected (n = 47) individuals divided into two groups: asymptomatic (ASY)/persistent generalized lymphadenopathy (PGL) and AIDS-related complex (ARC)/AIDS. RESULTS: Both HIV-1- and HIV-2-infected patients had significant reductions in the absolute number and percentage of CD4+ lymphocytes compared with seronegative individuals. No significant differences were found between HIV-2- and HIV-1 infected subjects in the same clinical stage. CD4+CD45RA+ cells were significantly reduced in HIV-1 and HIV-2 ARC/AIDS patients and mildly reduced in ASY/PGL HIV-1 and HIV-2 patients. There were no differences in the degree of reduction of CD4+CD45RO+ cells in ASY/PGL HIV-1 versus HIV-2 patients. However, in HIV-1-infected ARC/AIDS individuals the reduction in the percentage of this subset was more pronounced than in HIV-2 infection and this difference reached statistical significance. The increase in CD8+ lymphocytes (percentage and absolute number) was more pronounced in HIV-1 and the differences between HIV-1- and HIV-2-infected patients were statistically significant. CD8+CD45RO+ cells were significantly increased both in ASY/PGL and ARC/AIDS HIV-1-infected patients, whereas HIV-2-infected ASY/PGL patients had normal levels of these cells and HIV-2-infected ARC/AIDS patients had increases that were much less pronounced than that observed in HIV-1-infected ARC/AIDS patients. Significant differences in the absolute number and percentage of this subset between HIV-1- and HIV-2-infected individuals in similar clinical stages were found. CONCLUSIONS: HIV-2-infected individuals exhibit a lesser degree of depletion of memory CD4+ cells and a more limited expansion of CD8+CD45RO+ subset, which could be related to the putative lower immunopathogenicity of HIV-2. PMID- 7888113 TI - Antibodies to V3 loop peptides derived from chimpanzee lentiviruses and the divergent HIV-1ANT-70 isolate in human sera from different geographic regions. AB - OBJECTIVE: To study the spread of antibodies to V3 loop peptides of two chimpanzee lentiviruses and the divergent HIV-1ANT-70 isolate (group O) in human sera from different geographic regions, and to compare this with reactions to peptides from known North American (subtype B) and Zairean (subtype D) strains. METHODS: A total 2495 HIV-1-antibody-positive sera from nine countries were tested by enzyme-linked immunosorbent assay for antibodies to the V3 loop of 10 HIV/SIV isolates (including MN, SF2, HXB2, RF, MAL, ELI, Z6 and ANT-70 for HIV-1, and cpz-gab and cpz-ant for SIV). RESULTS: In each country, the highest prevalences were observed against the MN peptide (58.8-91.7%). Seroreactivity to other peptides from subtype B were generally lower. Prevalences of antibodies to V3 peptides derived from Zairean strains belonging to subtype D were generally lower than to subtype B. Relative high prevalences of sera reactive with the SIVcpz-gab V3 peptide were observed. The lowest rates were seen in Brazil (4.2%) and Belgium (25.7%). Among the African countries, the prevalence rates varied between 30.1 and 67.6%. Prevalence to the V3 loop derived from the SIVcpz-ant strains was much lower. Prevalence of sera reactive to the ANT-70 V3 loop peptide was very low, and the highest rates were observed in Cameroon (10.2%), Niger (6%) and Gabon (4.6%). Only the sera reactive to the ANT-70 V3 loop peptide from Cameroon and Gabon were confirmed on a specific HIVANT-70 Western blot (i.e., presence of antibodies to the envelope protein gp 120). CONCLUSIONS: The extent to which different V3 peptide reactivity patterns reflect the circulation of different HIV-1 strains in a particular population is not yet clear. However, V3 peptide serology using the very specific V3 peptide of the HIVANT-70 is a good indicator of the very aberrant group O in a particular population. PMID- 7888115 TI - Detection of HIV-1 proviral DNA in sperm from HIV-1-infected men. AB - OBJECTIVE: Sexual transmission is a major mode of the spread of HIV-1, although the cellular and molecular mechanisms are poorly defined. In this study, we sought to assess the cellular reservoirs of HIV-1 proviral DNA in the semen of HIV-1-infected men. DESIGN AND METHODS: An in situ polymerase chain reaction (IS PCR), which amplifies specific genes within intact cells, was used to evaluate levels of HIV-1 provirus in seminal cells from HIV-1-infected men in various stages of clinical disease. RESULTS: Initial studies demonstrated HIV-1 provirus in relatively low numbers (1:100 to 1:6000) of both the seminal mononuclear cells and sperm from certain HIV-1-infected men. To extend these findings, 94 seminal samples from HIV-1-infected men were evaluated. HIV-1 proviral DNA was detected in seminal cells of a significant percentage of HIV-1-infected men (45%) at all stages of clinical immunodeficiency. Both seminal mononuclear cells and sperm (35 and 33% of samples studied, respectively) harbored HIV-1 proviral sequences. HIV 1-harboring sperm are shown to stain positively for HIV-1 in the mid-pieces of these cells, with rarer staining of the sperm heads. CONCLUSIONS: HIV-1 proviral DNA can be demonstrated by IS-PCR in seminal mononuclear cells and sperm from certain HIV-1-infected men. The role played by proviral DNA in these cells in the sexual transmission of this retroviral agent will require further study. PMID- 7888116 TI - The regulation of HIV by retinoic acid correlates with cellular expression of the retinoic acid receptors. AB - OBJECTIVES: To analyze the effect of retinoic acids (RA) on HIV-1 expression and correlate this effect with expression levels of RA receptors (RARs) in T-lymphoid and monocytoid cell lines. DESIGN AND METHODS: The effect of all-trans and 9-cis RA on HIV-1 production in T-lymphoid (H9, CEM) and monocytoid (U937,THP-1) cell lines was measured during acute and chronic infection. The expression levels of human RAR alpha (hRAR alpha, receptor for all-trans RA) and the human retinoid-X receptor alpha (hRXR alpha receptor for 9-cis RA) were determined by Northern blot analysis. RESULTS: Both all-trans and 9-cis RA inhibited virus replication in HIV-1 IIIB-infected monocytoid cells, in the presence and absence of the co stimulatory agent phorbol myristate acetate (PMA). The retinoids had weak or no stimulatory effects on HIV production by T-cell lines. HIV production by PMA stimulated T-cell lines was inhibited by these retinoids. The 9-cis RA was generally more effective than all-trans RA in inhibiting HIV production and in combination generally more effective than the single agents alone. Human RAR alpha was expressed in H9, U937 and THP-1 cells, but almost undetectable in CEM cells. Human RXR alpha was significantly expressed in U937 and THP-1 cells, weakly expressed in H9 cells and not detectable in CEM cells. After stimulation by PMA, RXR alpha expression increased in H9 and U937 cells but not in CEM cells. Human RAR alpha expression was unchanged in H9 and CEM cells, and elevated in U937 cells, after PMA stimulation. CONCLUSION: The effect of RA on HIV-1 expression was cell-type-dependent and partially correlated with cellular expression of RARs. Endogenous or exogenously administered RA may have a significant role in HIV regulation. PMID- 7888117 TI - Pharmacokinetic variability of zidovudine in HIV-infected individuals: subgroup analysis and drug interactions. AB - OBJECTIVE: To investigate determinants of inter- and intraindividual variability of zidovudine (ZDV) pharmacokinetics in HIV-infected patients. DESIGN: A prospective study in a general 525-bed hospital with special funding for treatment and research of HIV-infected patients. METHODS: Serial blood samples were collected from 68 HIV-infected individuals providing a total of 95 pharmacokinetic curves. ZDV was measured with high-performance liquid chromatography and radioimmunoassay. Pharmacokinetic parameters were calculated by non-compartmental analysis. Patient characteristics were investigated by multivariate analysis for an influence on ZDV pharmacokinetics. RESULTS: Apparent ZDV clearance was significantly lower in patients with a lower body weight, in women, and in patients with a more advanced stage of HIV disease. Co administration of methadone with ZDV resulted in higher plasma concentrations of ZDV, while rifampin and ganciclovir increased apparent ZDV clearance. Age, the duration of ZDV use, CD4+ cell count, creatinine clearance, elevated serum liver enzyme levels, and the use of 11 other co-administered medications were not independently related to apparent ZDV clearance. CONCLUSIONS: The pharmacokinetic profile of ZDV in several subpopulations has been evaluated, as well as the observation of possible drug-drug interactions between ZDV and 14 different drugs or groups of drugs. These data suggest that patient-individualized antiretroviral therapy may be appropriate once pharmacokinetic-pharmacodynamic relationships have been established. PMID- 7888118 TI - Polymerase chain reaction for Toxoplasma gondii DNA in the cerebrospinal fluid of AIDS patients with focal brain lesions. AB - OBJECTIVE: To study the accuracy of polymerase chain reaction (PCR) for Toxoplasma gondii DNA in the cerebrospinal fluid (CSF) of AIDS patients for the diagnosis of T. gondii encephalitis. PATIENTS: Eighty-two AIDS patients with brain lesions. At autopsy, 19 patients (group A) had toxoplasmic encephalitis and 33 (group B) primary brain lymphoma or other infections. Brain histology was not available for 30 patients; cerebral lesions improved after anti-Toxoplasma therapy in 16 (group C), but there was no improvement in 14 patients (group D). METHODS: T. gondii RH strain was serially diluted in microplate wells. After heat denaturation, nested PCR was performed on diluted tachyzoites and on 10 microliters CSF with primers flanking the B1 repetitive region of T. gondii genome. RESULTS: DNA from one to five tachyzoites was detected in each experiment. PCR was positive in eight (42.1%) out of 19 group A samples, none of the group B samples, 10 (62.5%) out of 16 group C samples and none of the group D samples. Among group A and C patients, PCR was positive in all 11, and in seven out of 24 (29.1%; P < 0.04) patients who had received anti-Toxoplasma therapy for less or more than 1 week at the time of rachicentesis, respectively. CONCLUSIONS: Nested PCR for T. gondii in CSF may improve early differential diagnosis of AIDS associated focal brain lesions. Higher diagnostic accuracy was achieved when lumbar puncture was performed in the first week of anti-Toxoplasma therapy. PMID- 7888119 TI - Risk factors for HIV infection among drug users in Yunnan province, China: association with intravenous drug use and protective effect of boiling reusable needles and syringes. AB - OBJECTIVES: To characterize the prevalence and correlates of HIV infection among drug users in southwestern China. METHODS: Drug users in Longdao village, Yunnan Province underwent standardized interview and voluntary HIV serologic testing in a cross-sectional study. Analyses of potential risk and protective factors were stratified by method of drug use. RESULTS: Of 182 participants, 79 (43%) were HIV 1-seropositive. HIV seropositivity was found in 51 (80%) of the 64 intravenous drug users (IVDU) and 28 (24%) of the 118 who acknowledged use of drugs only by smoking [odds ratio (OR), 12.6; 95% confidence interval (CI), 5.7-28.5]. Among IVDU, reported sterilization of reusable injection equipment by boiling before intravenous drug use was associated with significant protection (adjusted OR, 0.16; 95% CI, 0.03-0.87). This protective association was also significant among the subset of IVDU who shared reusable injection equipment. CONCLUSIONS: HIV infection among drug users in Yunnan Province was highly correlated with intravenous drug use. The protective effect of sterilization of reusable injection equipment by boiling could be easily integrated into health education programs among IVDU in China and other rural Asian settings where reusable injection equipment is used. PMID- 7888120 TI - Demographic impact of HIV infection in rural Rakai district, Uganda: results of a population-based cohort study. AB - OBJECTIVES: To examine HIV-1-related mortality and demographic impact in a high HIV prevalence rural district of Uganda. DESIGN: One-year follow-up (1990-1991) in a population-based rural cohort. SETTING AND PARTICIPANTS: Annual enumeration of all consenting residents of 1945 households in 31 randomly selected community clusters in Rakai District. Subjects provided yearly HIV serological samples, behavioral and health information. MAIN OUTCOME MEASURE: Mortality in HIV infected and uninfected persons. RESULTS: Mortality among HIV-seropositive adults aged > or = 15 years of 118.4 per 1000 person-years (PY) was substantially higher than in HIV-seronegative adults [12.4 per 1000 PY; relative risk (RR), 9.5; 95% confidence interval (CI), 6.0-14.9]. Infant mortality among offspring of HIV infected mothers was almost double that for uninfected women (210 compared with 111 per 1000 live births; RR, 1.9; 95% CI, 1.0-3.5). Adult HIV-related mortality was associated with HIV prevalence and, in this cohort, with higher education, non-agricultural occupation and residence in roadside trading centers. We estimate that adult HIV prevalence in the district is 13% and adult HIV attributable mortality 52%. For all ages combined, district HIV attributable mortality is 28%. CONCLUSION: HIV is the leading cause of adult death in Rakai. Its effects on mortality are particularly marked in the most economically active sectors. However, the overall crude birth rate in the district (45.7 per 1000 population) remains higher than the crude death rate (28.1 per 1000 population), resulting in continued rapid population growth. PMID- 7888121 TI - Sensitivity of HIV-antibody assays determined by seroconversion panels. AB - OBJECTIVES: To determine the sensitivity of HIV-antibody assays for detecting low levels of HIV antibody using seroconversion and other panels containing plasma of varying titres. METHODS: Eight HIV-antibody assays, available under the World Health Organization bulk-procurement agreement, were evaluated on sets of sequential plasma samples derived from 11 individuals who had recently become HIV infected (seroconversion panels). In addition, two non-seroconversion panels, consisting of low performance (titre) and mixed titre samples were used to further define the sensitivity of the assays. The eight assays included two rapid tests, one simple test, and five enzyme-linked immunosorbent assays (ELISA). RESULTS: On average, the eight assays detected antibody 0.5-4.8 days later than the reference test (Abbott HIV-1/HIV-2 3rd generation ELISA); these differences were statistically significant for six of the eight tests. All tests performed well on the low performance and mixed titre panels. All eight assays also had comparable sensitivity to that of the reference test on a large panel of known positive plasma. The additional risk of missing an infectious unit of blood during seroconversion by using the least sensitive rather than the reference test was estimated to be 1 in 7600 and 1 in 76 million at annual HIV incidence rates of 1 and 0.0001%, respectively. The cost of eliminating this additional risk by using the reference test is between US$ 15,150 and 151 million per unit detected at the above incidence rates. CONCLUSIONS: Although there are differences in sensitivity between the assays when used to test blood from individuals during the course of seroconversion, the differences are small, and all eight tests are appropriate for use as screening tests. PMID- 7888122 TI - Death from suicide and overdose among drug injectors after disclosure of first HIV test result. AB - OBJECTIVE: To investigate whether notifying injecting drug users (IDU) of their positive HIV serostatus contributes to suicide and overdose mortality risk. DESIGN: Members of a cohort of IDU, recruited since December 1985, who first learned their HIV serostatus after study entry but before December 1992, were studied for incidence of deaths due to suicide and overdose. METHODS: Incidence of mortality due to suicide/overdose was calculated from date of first HIV test result disclosure until the end of follow-up or diagnosis of AIDS. RESULTS: Eighty-six HIV-positive and 252 HIV-negative IDU were included with median follow up times of 4.3 and 4.0 years, respectively. Seven suicides and 10 deaths from overdose were recorded. High suicide/overdose risk shortly after test result notification was not found among HIV-positive IDU. Only one out of eight HIV positive IDU who died of suicide/overdose died within 6 months of first disclosure. The overall suicide/overdose mortality rate was higher for HIV positive than HIV-negative IDU; the rate ratio being 2.46 [95% confidence interval (CI), 0.95-6.39] or 2.04 (95% CI, 0.77-5.39) after control for confounders. CONCLUSIONS: Notifying IDU of their positive HIV serostatus does not appear to lead to a sudden and substantial rise in suicide/overdose deaths. Although death from suicide/overdose is more common among HIV-positive than HIV negative IDU, this difference is likely to result from factors other than test result disclosure. Therefore, provided that appropriate counselling is offered, we see no reason to discourage voluntary HIV test result notification for fear of inducing suicide in HIV-infected IDU. PMID- 7888123 TI - CD26 is not involved in infection of peripheral blood mononuclear cells by HIV-1. PMID- 7888124 TI - In vitro immunoglobulin synthesis as a CD4+ lymphocyte depletion predictor in HIV 1-infected asymptomatic haemophiliacs. PMID- 7888125 TI - Infectivity and virulence of cell-associated SIVmac after single passage in vivo. PMID- 7888127 TI - HIV-1 infection detected by polymerase chain reaction frequently precedes antibody seroconversion in drug users. PMID- 7888126 TI - HIV interaction with sperm. PMID- 7888128 TI - Testing for HIV antibody in saliva and HIV-testing centres. PMID- 7888129 TI - Stable prevalence of HIV-1 in African populations. PMID- 7888130 TI - Prognostic value of triglyceride levels in early HIV infection. PMID- 7888132 TI - Statistics from the World Health Organization. PMID- 7888131 TI - Cryptococcal meningitis in HIV-infected patients. PMID- 7888133 TI - Trinucleotide repeat elongation in the huntingtin gene in Huntington's disease patients from 85 French families. The French HD Research Group. AB - IT15 is a new gene encoding a protein named huntingtin; a polymorphic CAG repeat in the proposed open reading frame of IT15 has been characterized, and an elongation of this repeat has been correlated to Huntington's disease (HD). We have investigated the CAG repeat in the huntingtin gene in 85 unrelated French families with Huntington's disease. In 79 patients (from 60 families, where at least one HD DNA was available) we found repeat lengths of 37 to 100 units, in contrast to 11 to 35 CAG's on normal chromosomes. Comparison of repeat length and age at onset of disease symptoms in 71 individuals confirms an inverse correlation (r = -0.51 for p < 10(-4)) between the age at onset and the number of CAG repeat units. PMID- 7888134 TI - Family studies in Prader-Willi syndrome. AB - Clinical, cytogenetic and molecular studies have been undertaken in the families of 52 probands with Prader-Willi syndrome. The maternal age at the birth of a proband with a deletion in 15p11q13 was on average 8 years less than that of the mothers of probands with uniparental disomy (UPD), the paternal age was on average 7 years less. Seven probands with UPD were all female, as were 7 patients who had neither a detectable chromosomal abnormality nor UPD. Cytogenetic and molecular polymorphisms in proximal chromosome 15 indicated that for probands with a 15q11q13 deletion, inheritance of both the maternal and the intact paternal homologue is random in their unaffected sublings. Pigmentation studies suggest that probands who have a deletion in 15q11q13 have lighter colouring than other family members implying that D15S12 may not be imprinted. PMID- 7888135 TI - Costello syndrome: a postnatal growth retardation syndrome with distinct phenotype. AB - In this report we describe two non-related patients, a 12-year-old girl and 3 6/12-year-old boy, with Costello syndrome. Costello syndrome is a true MCA/MR syndrome with severe postnatal growth retardation as the first clinical sign. Characteristic facial changes, loose, hyperelastic skin and papillomata become progressively more evident with age. Patients with Costello syndrome present a pleasant, happy nature and are mildly to moderately mentally retarded. PMID- 7888136 TI - Aminopterin Syndrome Sine Aminopterin (ASSA) syndrome in two siblings: further delineation of the syndrome and review of the literature. AB - In this report we describe two sibs with an unusual and complex pattern of severe malformations resembling Aminopterin Syndrome Sine Aminopterin (ASSA) syndrome, the phenotypic features of which are similar to those of aminopterin embryopathy. Six nonfamilial cases of ASSAS have been published in the literature to date. Our family with two affected sibs of different sexes supports the previous suggestion of autosomal recessive inheritance. Consanguinity of parents was excluded in this family, just as in all of the previously reported cases. Similar cases from the literature are briefly reviewed. PMID- 7888137 TI - 46,XY/48,XYYY mosaicism case report and review of the literature. AB - A 46,XY (18.9%)/48,XYYY (81.1%) mosaicism in lymphocytes and a 48,XYYY karyotype in skin fibroblasts were found in a 37-year-old obese man suffering from dysplasia of the right hip. As other reported cases, he showed mental retardation and behaviour disturbances with agressiveness, sexual impulsions. Testicular biopsy revealed fibrohyalinization in about 10% of the tubules and subnormal spermatogenesis in the others. PMID- 7888138 TI - Detection of low level sex-chromosomal mosaicism. AB - In this report we present the cytogenetic findings of low frequency (X or Y) mosaicism (1.0%-3.6%) in six patients aged between 28 and 36 years (average age 32.17) among sixteen individuals (analysis of 5402 mitoses) referred for genetic counseling after unsuccessful assisted reproductive treatment. For the detection of low level mosaicism, analysis of 500 metaphases is necessary to prove the presence of 1% abnormal clones, if the "background" level of the same aberraitons in controls is 0.1%. Low frequency mosaicism of sex chromosomes may be responsible for the unsuccessful results of in vitro fertilization and related techniques. The question may be raised whether diagnosis in subsequent pregnancies is indicated in these patients. PMID- 7888139 TI - Hypospadias as a new congenital anomaly in Bowen-Conradi syndrome. PMID- 7888140 TI - Osteopoikilosis: report of a familial case. AB - We describe four members of a family in which the clinical and radiological findings lead to consider the diagnosis of osteopoikilosis. The symptoms in all affected members were only those referred to as typical radiological features; these features became more extensive with older age. None of the subjects showed the skin lesions reported in the Buschke-Ollendorff syndrome. The importance of a suitable differential diagnosis is emphasized in order to avoid dangerous and unnecessary treatments. PMID- 7888141 TI - A deletion of 1.6 Kb proximal to the CGG repeat of the FMR1 gene causes fragile X like psychological features. AB - In this report we present the results of psychological investigations in a family in which 11 individuals, 7 females and 4 males, have a deletion of 1.6 Kb proximal to the CGG repeat of the FMR1. All 4 males with the deletion and 2 of the female carriers show characteristics of the fragile X clinical and behavioural phenotype. The findings in the present family illustrate that the typical characteristics of the fragile X syndrome can be caused by other types of mutations involving the FMR1 than the highly expanded stretches of CGG repeats in the 5' noncoding region of the FMR1 gene, coinciding with abnormal methylation patterns in that area as present in the vast majority of individuals with the fragile X syndrome. PMID- 7888142 TI - Catel-Manzke palatodigital syndrome in a second trimester female foetus with nuchal oedema, costovertebral anomalies and radial ray defect. AB - We present a female fetus with combination of Pierre Robin anomaly and nuchal oedema, bilateral radial defects, multiple hand malformations including bilateral hyperphalangy, brachymesophalangy, costovertebral abnormalities, and complex cardiac malformation. The present findings constitute a true MCA syndrome with uncertain pattern of inheritance. PMID- 7888144 TI - Borderline intelligence and discrete craniofacial dysmorphism in an adolescent female with partial trisomy 7p due to a de novo tandem duplication 7 (p15.1- >p21.3). PMID- 7888143 TI - The facio-digito-genital syndrome (Aarskog syndrome): a further delineation of the distinct radiological findings. AB - The Aarskog syndrome is a true MCA syndrome with X-linked recessive inheritance. The clinical phenotype, and its evolution with age, have been well documented in the past. Few data are reported on the radiological skeletal changes and findings. The purpose of the present paper is to describe the clinical and radiological findings in two brothers with Aarskog syndrome and to further delineate the radiological characteristics of this condition. The main findings are asynchronic and delayed bone age, shortened long tubular bones with wide metaphyses, brachyphalangy, hypoplasia of the middle phalanges of the fifth fingers, short and broad first metacarpals and metatarsals and pelvic hypoplasia. PMID- 7888145 TI - The NMDA antagonist procyclidine, but not ifenprodil, enhances the protective efficacy of common antiepileptics against maximal electroshock-induced seizures in mice. AB - Procyclidine (up to 20 mg/kg i.p.) did not influence the electroconvulsive threshold per se, but when given in a dose of 10 mg/kg, it potentiated the protective activity of carbamazepine, diphenylhydantoin, phenobarbital and valproate, and in a dose of 20 mg/kg, that of diazepam against maximal electroshock-induced convulsions in mice. Ifenprodil increased the threshold for electroconvulsions when applied at 20 and 40 mg/kg (i.p.), but surprisingly, when combined with all antiepileptics tested, it did not influence their anticonvulsant actions. The chimney test in mice revealed, that application of procyclidine at 10 mg/kg together with phenobarbital and valproate, and procyclidine at 20 mg/kg with diazepam resulted in motor impairment. However, when procyclidine was applied at 10 mg/kg together with carbamazepine or diphenylhydantoin, no motor impairment was noted. The combined treatment of procyclidine (10 mg/kg) with carbamazepine, diphenylhydantoin, phenobarbital or valproate, as well as procyclidine (20 mg/kg) with diazepam caused significant worsening of long-term memory. Finally, procyclidine did not alter the total plasma levels of carbamazepine, diazepam, diphenylhydantoin, phenobarbital and valproate. It may be concluded that not all agents interfering with NMDA receptor complex-mediated events lead to the potentiation of the anticonvulsant activity of antiepileptic drugs. PMID- 7888146 TI - Different effects of scopolamine on extracellular acetylcholine levels in neostriatum and nucleus accumbens measured in vivo: possible interaction with aversive stimulation. AB - The in vivo microdialysis technique was used to measure extracellular concentrations of acetylcholine (ACh) in the neostriatum (NS) and nucleus accumbens (NAc) of freely moving rats after intraperitoneal administration of the muscarinic receptor antagonist scopolamine (0.5 mg/kg) or vehicle. Simultaneously, behavior was monitored. The administration of scopolamine induced an increase in extracellular ACh levels in the NS, which reached a maximum of about 185% within one hour after injection and returned to baseline values about three hours after injection. In the NAc, an increase of similar time-course was observed; however, this increase reached a maximum of 250%, which was significantly higher than the one observed in NS. These changes in ACh levels were accompanied by enhanced locomotion, rearing and grooming; however, the behavioral changes were of shorter time-course than those of extracellular ACh. The injection of vehicle did not affect ACh levels in NS, but induced a significant increase (60%) in the NAc. The levels of behavioral activity after vehicle injection did not differ from pre-injection levels. These results suggest, that the cholinergic systems in the NAc and NS are differently affected by peripheral administration of both scopolamine and vehicle. The differential effects of scopolamine in NS and NAc could reflect pharmacodynamic differences between these two striatal brain areas, perhaps due to a higher density of cholinergic interneurons or muscarinic autoreceptors in the NAc in comparison to the NS. However, the increase of extracellular ACh observed after vehicle injection suggests that factors such as aversive stimulation through the injection procedure can increase ACh release in the NAc and that such a mechanism can interact within the action of scopolamine. Thus, the stronger action of scopolamine on extracellular ACh in the NAc might be an additive effect of the drug with that of the injection procedure. PMID- 7888147 TI - [3H]paroxetine and [3H]citalopram as markers of the human brain 5-HT uptake site: a comparison study. AB - The binding of [3H]paroxetine and [3H]citalopram to the human brain serotonin (5 HT) uptake site has been characterized and compared. Our results reveal that the binding exclusively involved with the 5-HT uptake site is identical for both [3H]ligands. The selective 5-HT uptake inhibitor citalopram displays the highest affinity for this uptake site, as compared with the affinities obtained for desipramine and norzimeldine, which is in accordance with their respective blockage of 5-HT uptake. Similar Bmax values were obtained for both radioligands in the brain regions studied, indicating their binding to the same presynaptic membrane protein. Together these findings suggest that both [3H]paroxetine and [3H]citalopram are good markers of the 5-HT transporter as both bind selectively and with high affinity to the serotonin uptake sites. However, the higher affinity of [3H]paroxetine confirms that this compound is the best radioligand for the 5-HT uptake site available today. PMID- 7888148 TI - Effects of subacute administration of methamphetamine and nicotine on locomotor activity in transgenic mice expressing the human tyrosine hydroxylase gene. AB - We produced transgenic (Tg) mice carrying the human tyrosine hydroxylase (TH) gene. To investigate differences in the dopaminergic (DAergic) neuronal activity between the Tg and nTg mice, we examined changes in the locomotor activity induced by methamphetamine (MAP) and nicotine (NIC), which enhances DA release and induces TH enzyme activation, respectively. Surprisingly, however, the intensity of MAP (2.5 mg/kg, once a day for 14 days)-induced hyperlocomotion in the nTg mice was greater than that in the Tg mice, and, furthermore, the Tg mice were less sensitive to subacute administration of NIC (0.5 mg/kg, once a day for 14 days) than the nTg mice. These results suggest that DAergic neuronal function is suppressed in Tg mice to compensate for the overexpression of TH. PMID- 7888149 TI - Alterations in dopamine and serotonin uptake systems in the striatum of the weaver mutant mouse. AB - In the striatum of the homozygous weaver mutant mouse (wv/wv), dopamine content, uptake and tyrosine hydroxylase activity are decreased compared to wild-type (+/+) mice. In mice heterozygous for the weaver gene (wv/+), these dopaminergic parameters exhibit only minor reductions compared to +/+ mice. The wv/wv striatum has recently been shown to have an increase in serotonin content. In the present study, the serotonin uptake system of the weaver striatum was investigated. Synaptosomal uptake of [3H] serotonin was determined in the dorsal portion of wv/wv and +/+ striatum, and serotonin uptake sites were examined by the binding of [3H] citalopram in the striatum of wv/wv, wv/+ and +/+ mice. The dopamine uptake system was also investigated in all three genotypes via the binding of [3H] mazindol. Synaptosomal uptake of [3H] serotonin was increased by 79% in the dorsal portion of the wv/wv striatum compared to that seen in the +/+ striatum. The binding of [3H] citalopram was increased by 62% in the dorsolateral and by 111% in the dorsomedial portions of the wv/wv striatum compared to +/+. [3H] Citalopram binding in the wv/+ striatum was also higher than +/+, but this increase did not reach statistical significance. Within the wv/wv striatum, [3H] mazindol binding was almost completely absent (88-89% reduction) in the dorsal portion and severely reduced in the other striatal areas. These data support the notion that the dorsal portion of the wv/wv striatum, which has the severest reduction in dopamine uptake, is hyperinnervated by serotonin fibers. PMID- 7888150 TI - Cyclic AMP-induced depolarization measured by bis-oxonol fluorescence in bovine adrenal medullary chromaffin cells. AB - Effects of cyclic AMP on membrane potentials were examined by measuring the changes of bis-oxonol fluorescence in bovine adrenal medullary chromaffin cells. 8-Bromo cyclic AMP (8Br-cAMP) or forskolin caused a gradual and long lasting increase of the fluorescence intensity. The effects of 8br-cAMP was blocked by cyclic AMP-dependent protein kinase inhibitor, adenosine-3', 5'-cyclic monophosphothioate, Rp-diastereomer (Rp-cAMPS) and there was no further increase in the fluorescence by 8br-cAMP in the cells depolarized with 56 mM KC1 or gramicidin D. Ouabain or the removal of extracellular K+ ([K+]0 free) which block Na+, K+-ATPase also increased the fluorescence. The effect of 8br-cAMP on the fluorescence was counteracted by ouabain or [K+]0 free and was blocked in the absence of extracellular Na+ but not by tetrodotoxin or the removal of Ca2+ from the medium. These results may suggest that cyclic AMP causes the membrane depolarization by accumulating Na+ through the inhibition of Na+, K+-ATPase in adrenal chromaffin cells. PMID- 7888151 TI - Insulin-like growth factor-1 receptors in human spinal cord: changes in amyotrophic lateral sclerosis. AB - Neurotrophic factors are important for neuronal survival and maintenance in the adult nervous system. The regional distribution of insulin-like growth factor-1 (IGF-1) receptors in human spinal cords from controls and amyotrophic lateral sclerosis (ALS) patients was studied by immunohistochemistry and quantitative autoradiography. When comparing 125I-IGF-1 binding in the different spinal levels of normal spinal cord the same distribution pattern was found in which the binding was highest in the central canal > dorsal horn > ventral horn > white matter. In the ALS cases although a general upregulation of IGF-1 receptors was observed throughout the spinal cord, significant increases were observed in the cervical and sacral segments compared to controls. IGF-1 receptor immunoreactivity showed a similar pattern to that for 125I-IGF-1 binding, with immunoreactivity being found in the gray matter of the spinal cord and enhanced immunoreactivity occuring in ALS patients compared to controls. In agreement with the distribution of IGF-1 receptors, IGF-1 immunoreactivity was found within the gray matter of the spinal cord. The cartography of IGF-1 receptors in the normal spinal cord as well as the change of these receptors in diseased spinal cord may be of importance in future treatment strategies of ALS. PMID- 7888153 TI - The effects of Alzheimer disease on driving-related abilities. AB - Ten Alzheimer disease (AD) patients and 12 healthy elderly controls were evaluated on two tests of driving-related abilities: the Driver Performance Test (DPT) and the Driving Advisement System (DAS). Subjects were administered a battery of neuropsychological tests to determine if severity of dementia in AD correlates with driving performance. On the DPT, the AD patients scored in the average range in two of five skill areas (predicting the effects of a hazard, deciding how to avoid it); below average in two areas (searching for a hazard, executing evasive actions); and poorly in one area (identifying hazards). The elderly controls scored at an average level in all five skill areas. On the DAS, AD patients were significantly slower than the elderly controls on simple, two choice, and conditional reaction time tests and were much slower than drivers in general. The AD patients' performances on two cognitive tests, the Mini-Mental State Examination (MMSE) and the Category Fluency Test, correlated significantly with aspects of performance on the DPT and the DAS. Although these are preliminary results from a pilot investigation, they suggest that AD patients' driving-related abilities are adversely affected by the disease and that driving related performance tests and neuropsychological tests may be useful in assessing the impact of AD on driving. PMID- 7888152 TI - Neurofibrillary pathology in brains of elderly schizophrenics treated with neuroleptics. AB - The clinical histories of 102 schizophrenics who died at 70 years of age or older were reviewed. The incidence of neurofibrillary tangles (NFTs) was two times higher in the patients who received (74%) than in those who did not receive (36%) treatment with neuroleptics. The development of NFTs started earlier in the treated group. Further studies comparing brains of nine schizophrenics (average age, 86 years) who did not receive treatment with neuroleptics and seven age matched cases who received neuroleptics, both with neurofibrillary pathology and neuritic plaques, showed characteristic differences. The numerical density of NFTs was slightly greater in the cornu Ammonis (CA1 and CA2) and subiculum of treated patients. Significantly lower numerical density and lower percentage of pretangles (stage 0) and early and mature tangles (stages 1 and 2) and increased number of end-stage tangles (stage 3) were found in the CA, subicular complex, and cerebral cortex of the treated group. These changes suggest accelerated neurofibrillary degeneration in neurons. A significant increase in the numerical density of tau-1-positive plaques was observed in sector CA1 of the CA (from 0.15/mm2 to 17.36/mm2), subiculum (from 0/mm2 to 16.62/mm2), temporal cortex (from 0.14/mm2 to 9.46/mm2), and occipital cortex (from 0.08/mm2 to 0.39/mm2). The higher numerical density of tau-1-positive plaques, but not of 4G8-positive plaques, indicates acceleration of neurofibrillary changes in the plaques of patients treated with neuroleptics. The significant decrease (20-25%) in the numerical density of neurons in the pyramidal layer of sectors 2-4 in the CA appears to be associated with accelerated neurofibrillary changes in neurons and plaques in the treated group. This study demonstrates that chronic treatment with neuroleptics--not schizophrenia itself--significantly increases the risk of more frequent, earlier, and accelerated development of neurofibrillary pathology in the brains of elderly schizophrenics. PMID- 7888154 TI - Cerebrospinal fluid of patients with senile dementia of Alzheimer's type shows an increased inhibition of alpha-chymotrypsin. AB - The inhibition of alpha-chymotrypsin induced by cerebrospinal fluid from patients with senile dementia of Alzheimer's type, vascular dementia, and nondemented controls was investigated. We optimized the sensitivity of the assay so that the inhibition of alpha-chymotrypsin could be measured in all samples. The competitive inhibition was proportional to the amount of cerebrospinal fluid (CSF) added to the reaction mixture. After correction for protein concentration, the inhibition was higher with CSF from patients with senile dementia of Alzheimer's type than with those from patients with vascular dementia or controls. Inhibitory activity appeared to be specific for alpha-chymotrypsin because no inhibition for papain was found. Moreover, the depletion of alpha 1 antichymotrypsin from CSF by immunoadsorption revealed that this serpin was responsible for the disappearance of the inhibitory activity. Our findings suggested that the increased alpha-chymotrypsin inhibitory activity might represent an in vivo functional index of an abnormal protease metabolism in patients with Alzheimer's disease. PMID- 7888155 TI - Prolonged latencies of pattern reversal visual evoked early potentials in Alzheimer disease. AB - We studied patients with Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis (ALS) with a pattern reversal (checkerboard light diode) visual evoked potential (VEP) paradigm to observe the involvement of the visual system in these primary neurodegenerative diseases. All patients were in the mild or moderate stage of the disease. In Alzheimer disease there was a significant increase of the latency of the P55, N65, P100, and N130 components, as well as an increase of the P55-P100 interpeak latency, compared with matched normals. These alterations indicate dysfunction of both the retinocalcarine pathway and the cortex. Patients with Parkinson disease revealed a significant delay of the N130 component only. Patients with ALS had normal latency values of all VEP components. The P100-N130 amplitude was diminished in all these disease groups compared with age-matched controls. PMID- 7888156 TI - Current status of telepathology. AB - Telepathology is moving from the experimental stage to become a regular feature of pathology practice. This has been made possible by technical advances in telecommunications and image processing. Since 1990 the University Hospital of Tromso has provided local hospitals in northern Norway with a remote frozen section service and with access to video conferences for the review of microscopic findings and for the discussion of major diagnostic issues. Several other hospitals in Norway are now participating in this development and practical relations among pathology laboratories for the purpose of consultation and education will be the next step in the procedure. Similar developments in telepathology have taken place in other countries. Standardization of network and telepathology workstations will be needed before extensive international collaboration can be achieved. Progress in high quality video devices, high capacity telecommunication lines and improved image compression techniques will increase the usage of telepathology services and make them cost-effective. Thus, telepathology will contribute to the development of pathology services in the next century. PMID- 7888157 TI - Staphylococcal neutral phosphatase. A highly cationic molecule with binding properties for immunoglobulin. AB - Staphylococcal neutral phosphatase (NPtase) was purified from two Staphylococcus aureus strains by sequential high salt extraction, ultracentrifugation and ion exchange chromatography. The enzyme showed maximum phosphatase activity at neutral pH, appeared as two bands in SDS-PAGE (31 and 32 kDa), and the isoelectric point was > 10. No close similarity between NPtase and other known bacterial proteins in respect of their N-terminal amino acid sequences was found. Purified NPtase bound rat and human polyclonal IgG [intact and F(ab')2 fragments], IgM, IgA, intact myeloma immunoglobulins, myeloma light chains, gamma heavy chain and, with a much lower affinity, Fc fragments. Furthermore, NPtase can bind serum albumin. Heparin, a highly negatively charged molecule, significantly inhibited NPtase binding to immunoglobulins and HSA, but did not inhibit the binding of specific antibodies to NPtase; this indicates that charge interactions are important. The newly characterized staphylococcal phosphatase with binding properties for immunoglobulin is an interesting bacterial protein that could be involved in post-infectious sequelae. PMID- 7888158 TI - Ultrastructural localization of monoclonal antibodies against Pneumocystis carinii. Differentiation between developmental stage and host origin. AB - The ultrastructural immunolocalization of target antigens recognized by two monoclonal antibodies against Pneumocystis carinii was investigated using both human- and rat-derived organism. Labelling was seen using both cryo electron microscopy and postembedding in Epon after fixation in glutaraldehyde. The antibodies showed different host species- and developmental stage specificity. One of the antibodies reacted with the outer membrane of all developmental stages of human-derived but not rat-derived organisms, whereas the other reacted only with the cyst form. The distribution of the latter was similar to that reported for methenamine silver, a widely used cytochemical stain for the parasite, and reacted with both human- and rat-derived organisms. The antibodies described appear to be useful markers in studies on the differentiation of Pneumocystis carinii. PMID- 7888159 TI - Priming of oxidative response in human neutrophils by anti-CD18 monoclonal antibodies. AB - Type I collagen, the most abundant protein in the body, after acid extraction adheres to and can induce a respiratory burst from neutrophils. It has been proposed that the effects of collagen are mediated via the CD18 subfamily of integrins. In the present study, adhesion was measured by affinity chromatography in a column containing collagen-coated microcarriers, while oxygen metabolite production was measured with luminol-dependent chemiluminescence. Neutrophil adherence to collagen was attenuated by anti-CD18 monoclonal antibodies. The respiratory burst in response to collagen was not affected by the antibodies. Incubation of neutrophils with anti-CD18 antibodies prior to stimulation with FMLP increased both the extra- and intracellular respiratory burst. Treatment with antibodies prior to PMA stimulation increased only the extracellular respiratory burst. In conclusion, the respiratory burst from neutrophils is primed by pretreatment with anti-CD18 monoclonal antibodies. The collagen stimulated respiratory burst is probably also primed, but the effect is hidden by the simultaneous attenuation of adhesion. PMID- 7888160 TI - Prognostic value of Ki-67 expression in 182 soft tissue sarcomas. Proliferation- a marker of metastasis? AB - Soft tissue sarcomas (STS) are characterized by deregulated proliferation. Ki-67 is a cell cycle antigen which may be elevated in proliferative states. We analysed Ki-67 expression in fixed and embedded tissues from STS in order to examine associations between proliferation, primary tumour characteristics, and metastasis. One hundred and eighty-two adult patients with trunk wall or extremity STS were treated at our institution between 1980 and 1992 (35 developed local recurrence and 56 developed metastases). Median follow-up time for survivors was 6 years (1-13). We used a semiquantitative score to the assess percentage of Ki-67-positive cells: < or = 10% (n = 86), > 10-25% (n = 57), > 25 50% (n = 30), > 50-75% (n = 7), > 75-100% (n = 2). Increasing Ki-67 expression correlated positively with tumour size, malignancy grade, necrosis, vascular invasion, S-phase fraction, and metastasis. A Ki-67 index Ki-D < or = 10% (n = 86) and > 10% (n = 96) defined two groups who had 84% and 56% 3-year metastasis free survival (p = 0.0001), respectively. Tumours with Ki-D > 10 were typically large, high grade, necrotic, DNA aneuploid, and had intravascular invasion and a higher S-phase fraction. Ki-67 expression may be helpful in predicting survival of patients with soft tissue sarcomas. PMID- 7888161 TI - Phase variation in streptococci of serological group B. Characteristic properties of isolates from human and bovine infection. AB - Encapsulation is thought to be a critical virulence factor in streptococci of serological group B. In the present study two encapsulated low-density variants could be separated from their unencapsulated original strains by Percoll gradient centrifugation. The original strains had been isolated from human endocarditis and bovine mastitis. Type antigen preparations of the encapsulated human and bovine group B streptococcus reacted with type III- and type IV-specific antiserum, respectively. No comparable reactions could be observed with their unencapsulated parent strains. In contrast to the original strains, the encapsulated variants grew with uniform turbidity in fluid medium and formed diffuse colonies in soft agar. The original strains grew as granular sediment and formed compact colonies in soft agar. In addition, the original strains appeared to have a more hydrophobic surface and showed significantly greater adherence to epithelial cells. In contrast to the nonencapsulated parent strains, the encapsulated variants were less phagocytosed by polymorphonuclear leukocytes. These findings may help our understanding of the pathogenic importance of phase variants in infections with this bacterial organism. PMID- 7888162 TI - The true extent of ulcerative colitis? A radiological, endoscopic and histological study. AB - Twenty-six radiological, endoscopic and histological examinations of the large bowel were performed in 25 patients with ulcerative colitis. Extensive colitis was observed in 42% of the radiological, in 38% of the endoscopic, and in 27% of the histological examinations. Agreement as to the extent of the colitis between all three examination methods was reached in 53% of the cases. The endoscopic extent of colitis varied between left-sided and extensive in 41% of the patients during a 7-year median follow-up. The frequent change in the extent of ulcerative colitis and the considerable disagreement between radiography, colonoscopy and histology in evaluating the extent of colitis justify the question, "Does a true, unambiguous extent of colitis really exist?" It is more likely that the extent of colitis is just a function of time and the examination method used. PMID- 7888163 TI - Toxic shock syndrome related to simultaneous Staphylococcus aureus epiglottic abscess and group A streptococcal pharyngitis with bacteremia. AB - A case of toxic shock syndrome (TSS) is reported in which both a TSST-1-producing Staphylococcus aureus strain and a group A beta-hemolytic streptococcal strain (GABHS) were involved. The S. aureus group I strain was isolated from an epiglottic abscess, and the GABHS strain from tonsils and blood cultures. Acute intubation was needed because of obstruction of the airways by swollen and hyperemic mucous membranes in the oro- and hypopharynx together with external edema around the neck. Intravenous therapy with penicillin G was instituted initially on account of GABHS cellulitis and bacteremia. The patient's condition deteriorated during this treatment, and improvement did not occur until drainage and intravenous dicloxacillin therapy was instituted. It is not possible in this case to draw any conclusions as to which of the two organisms caused the TSS or if they were both involved. PMID- 7888164 TI - Discriminating translation of insulin-like growth factor-II (IGF-II) during mouse embryogenesis. AB - The problem is to discover which of the promoters of the insulin-like growth factor-II gene stimulate the transcription of mRNA which is translated into protein. Three alternative leader exons are attached to the coding sequences in RNA transcribed from this gene in other systems, and it is mainly the paternal allele which is expressed in mouse development. Transcripts bearing each of the three leader exons were found in the RNA from the chorio-allantoic placenta, visceral yolk sac, and embryo, starting at 9.5 days. A varying proportion of one abundant transcript was disengaged from the polysomes at different days of development. This transcript was prefixed by the longest of the three alternative untranslated 5' leader exons (exon 2), and it was consistently associated with polysomes in the choroid plexus and leptomeninges of the brain. Many exon 2 transcripts were abbreviated by endonucleolytic cleavage and lacked a poly(A) tail. In contrast, the transcripts with the shortest leader (exon 3) were mainly displayed on polysomes at all the stages of development which were examined. During mouse development, the production of IGF-II protein must be partly controlled by the mechanisms which regulate translation. PMID- 7888166 TI - Relationships between biochemical markers for residual sperm cytoplasm, reactive oxygen species generation, and the presence of leukocytes and precursor germ cells in human sperm suspensions. AB - In this study, we have examined the relationship between creatine phosphokinase (CPK), a biochemical measure of human sperm quality (Huszar et al., 1988a,b, 1990; Huszar and Vigue, 1994), and a marker for the presence of residual cytoplasm in human spermatozoa, glucose-6-phosphate dehydrogenase (G6PDH). We then determined whether the diagnostic potential of these enzymes was related to the capacity of the sperm suspensions to generate reactive oxygen species (ROS) and/or the presence of leukocytes and precursor germ cells. Across the data set as a whole, G6PDH and CPK were highly correlated with each other and, to a lesser extent, with the generation of ROS. Contamination of the sperm suspensions with leukocytes might have contributed to these associations, since the presence of such cells was also significantly correlated with CPK, G6PDH, and ROS. However, even after the leukocytes had been carefully removed, G6PDH was still highly correlated with CPK (r = 0.794), indicating that both criteria were providing similar information of the cytosolic component of human sperm suspensions. In the absence of leukocyte contamination, CPK and G6PDH activities were also correlated with the presence of precursor germ cells, and this association may, in part, explain the diagnostic value of these criteria. An additional component of their prognostic value may be reflected in the statistically significant association observed between G6PDH activity and ROS generation. A possible mechanism for such an association is suggested, which should be amenable to experimental verification. PMID- 7888165 TI - Analysis of thymidine kinase gene expression in preimplantation mouse embryos. AB - Thymidine kinase (TK) activity was examined during the development of preimplantation mouse embryos. TK activity was increased approximately 20-fold from day 2 embryos (2-cell) to day 5 embryos (late blastocyst). TK activity did not change along with the progression into S-phase of the first and the second cell cycles but increased sharply at S-phase of the third cell cycle. Analysis of TK mRNA with a reverse transcription-polymerase chain reaction (RT-PCR) method showed that the level of TK mRNA was low in ovulated eggs and 1-cell embryos and was hardly detectable in day 2 embryos (2-cell), but sharply increased in day 3 embryos (mixture of 5- to 8-cell and morula). The functional role of 5'-flanking sequence of TK gene was also investigated in preimplantation embryos after microinjection with the DNA construct of 5'-flanking sequence of TK (2.4 kb) linked to bacterial lacZ gene (TK2.5lacZ) into the pronucleus of 1-cell and subsequently by histochemical staining with X-gal. beta-Galactosidase activity was first detected in day 3 embryos (8-cell), and 30% of embryos were stained with X-gal in day 4 and day 5 embryos, respectively. These results show that an increase in TK activity occurred after 2-cell stage, and this increase was primarily due to the embryonic activation of TK gene expression. Also, it appears that the 5'-flanking sequence of TK may directly regulate the TK gene expression at the transcriptional level during preimplantation murine development. PMID- 7888167 TI - Immunoglobulins from human follicular fluid induce the acrosome reaction in human sperm. AB - The ability of human follicular fluid (hFF), retrieved from women undergoing IVF to induce the acrosome reaction (AR) in human sperm has been documented by several laboratories. However, the nature of the active factors in the hFF and the physiological meaning of the AR induction are highly controversial. We performed a three step purification scheme for hFF and all the fractions were screened for the AR-inducing activity. AR activity was associated with a protein fraction of M(r) > 180 kD that on further analysis under PAGE was found to be composed by subunits of apparent M(r) 50,000 and 29,000. The N-terminal sequences of these bands showed a 100% homology with the heavy and light chains of human IgG. A polyclonal antibody raised against the purified protein and anti-human IgG were both able to suppress the acrosome reaction-inducing activity of crude hFF. However, neither normal human serum nor a purified preparation of human IgG were able to mimic the AR-inducing activity of hFF. We concluded that the AR-inducing activity of hFF is, at least in part, due to the presence of antisperm antibodies. PMID- 7888168 TI - Putative rat sperm lipid-binding protein: isolation and partial characterization. AB - Previous work has identified a prominent 22-24-kD protein that is present in rat male reproductive tissues, including epididymis and testis (Brooks, 1985; Jones and Brown, 1987; Moore et al., 1987). Using a monoclonal antibody (designated mAb B109) against this 24-kD antigen (referred to as B109), we have isolated the protein using a combination of chromatofocusing and electroelution from SDS-PAGE gels, and reverse phase HPLC. B109 (pI = 4.8) is amino-terminal blocked. To obtain internal amino acid sequences, the isolated protein was cleaved either with cyanogen bromide in 70% formic acid or with TLCK-treated chymotrypsin. With cyanogen bromide treatment, two peptides, 17.8 kD and 11.9 kD, were isolated and partial amino acid sequences obtained. Chymotryptic peptides were isolated by reverse-phase HPLC and two were chosen for sequence analysis. A computer search for sequence homology through the protein identification resource (PIR) matched B109 to a basic 21-kD cytosolic protein (pI = 7.4) found in bovine brain (> 80% homology). When peptide sequence differences obtained in the present study were substituted into the 21-kD cytosolic protein sequence obtained from the PIR using Intelligenetics software, the calculated pI dropped from 7.4 to 5.8, suggesting that pI differences between the bovine and rat molecules are the result of amino acid substitutions in the testis protein and not tissue-specific posttranslational processing. It has been postulated that the 21-kD bovine brain protein is associated with phospholipid transport, although the function of B109 is unknown. PMID- 7888169 TI - Calcium influx into mouse spermatozoa activated by solubilized mouse zona pellucida, monitored with the calcium fluorescent indicator, fluo-3. Inhibition of the influx by three inhibitors of the zona pellucida induced acrosome reaction: tyrphostin A48, pertussis toxin, and 3-quinuclidinyl benzilate. AB - The fluorescent calcium indicator, fluo-3, was loaded as the membrane permeant tetraacetoxymethyl (AM) ester into cauda epididymal mouse sperm at 25 degrees C for 20 min in the absence of bovine serum albumin (BSA) and presence of the dispersant, Pluronic F-127. Excess indicator was removed by two centrifugation washes at 100g for 10 min, a procedure that did not impair sperm motility. Upon resuspension in medium containing 20 mg/ml BSA to promote capacitation, the sperm cells exhibited readily detectable fluorescence uniformly distributed in the cytoplasm. Cell fluorescence was stable over the time of the experiments and was responsive to changes in intracellular calcium concentration, [Ca2+]i. Initial [Ca2+]i was 231 +/- 58 nM (+/- SE, n = 43). Addition of heat-solubilized mouse zonae pellucidae to capacitated sperm increased [Ca2+]i by 106 +/- 19 nM (+/- SE, n = 18), the higher steady-state concentration being reached after 30 min. Subsequent addition of the non-fluorescent calcium ionophore Br-A23187 resulted in a further increase of 114 +/- 18 nM (+/- SE, n = 18), the higher steady-state concentration being reached after 6 min. The increase in [Ca2+]i induced by solubilized zonae pellucidae was largely blocked by 3-quinuclidinyl benzilate (QNB), an antagonist of muscarinic receptors that was earlier shown to block the zona pellucida induced acrosome reaction in mouse sperm (Florman and Storey, 1982: Dev Biol 91:121-130). This [Ca2+]i increase was completely blocked by the tyrosine kinase inhibitor, tyrphostin A48, and by the inactivator of G1 proteins, pertussis toxin. At the concentrations at which they blocked the zona pellucida induced increase in [Ca2+]i, all three inhibitors also blocked the zona pellucida induced acrosome reaction. These results indicate that [Ca2+]i increase in is an early, if not the initial, reaction in the sequence leading to zona pellucida induced acrosomal exocytosis in mouse sperm. The observation that the three inhibitors, each having a different mode of action, all block the zona pellucida induced [Ca2+]i suggests that the sperm plasma membrane receptors mediating the zona pellucida induced acrosome reaction may function as a complex, whose formation is activated by zona pellucida ligand binding. PMID- 7888170 TI - Affinity binding of hamster oviductin to spermatozoa and its influence on in vitro fertilization. AB - The aim of this study was to determine the influence of hamster oviductal glycoprotein (oviductin) on in vitro gamete interaction. Oviductin was purified from the oviducts using lithium 3,5-diiodosalicylate, followed by phenol extraction. Immunocytochemistry using indirect fluorescence staining revealed that oviductin binds to the sperm anterior acrosomal region. The specific binding of oviductin resulted in inhibition of in vitro fertilization in studies using cumulus-free oocytes. The inhibitory effect was dependent on the concentration of oviductin and occurred in both ovarian and oviductal oocytes but not zona-free oocytes, indicating that sperm-zona interaction was interferred by oviduction. However, the inhibitory effect of oviductin in sperm-zona interaction was reduced when cumulus-enclosed oocytes from ovaries and oviducts were used, indicating that the egg investment including cumulus oophorus has some effect on oviductin sperm complex and maintaining the fertilizing ability. PMID- 7888171 TI - Anionic and cationic components from protein aggregates in bovine seminal plasma and their effects on sperm motility. AB - Bovine seminal plasma proteins are in an aggregated form of high molecular weight in their native state. By immobilisation on a cation exchanger with exposure to disaggregating conditions (i.e., acetonitrile and low pH), the high-molecular weight aggregates could be dissociated to slowly release the low-molecular-weight components. The anionic component released from the cation exchanger during disaggregation was collected by adsorption on a hydrophobic interaction column. The cationic component remaining on the cation exchanger was eluted with NaOH. Both components were found on gel permeation chromatography to be < 5 kDa. SDS PAGE of the various fractions showed that components of low molecular weight were still in an aggregated form. These components resulting from the disaggregation process have detrimental effects on sperm motility and the effects were more substantial compared with that of whole seminal plasma. All the cationic components were significantly detrimental to sperm motility, especially the fractions of low molecular weight. The anionic fractions reduced sperm motility when in an aggregated state. The isolated anionic peptide was not detrimental in its free form. In all fractions the peptides tended to re-aggregate to a higher molecular weight under neutral conditions, however, the isolated anionic peptide (molecular weight < 1,500) failed to do so. PMID- 7888172 TI - Amino acid transporters of lower eukaryotes: regulation, structure and topogenesis. AB - Lower eukaryotes such as the yeast Saccharomyces cerevisiae and the filamentous fungus Aspergillus nidulans possess a multiplicity of amino acid transporters or permeases which exhibit different properties with respect to substrate affinity, specificity, capacity and regulation. Regulation of amino acid uptake in response to physiological conditions of growth is achieved principally by a dual mechanism; control of gene expression, mediated by a complex interplay of pathway specific and wide-domain transcription regulatory proteins, and control of transport activities, mediated by a series of protein factors, including a kinase, and possibly, by amino acids. All fungal and a number of bacterial amino acid permeases show significant sequence similarities (33-62% identity scores in binary comparisons), revealing a unique transporter family conserved across the prokaryotic-eukaryotic boundary. Prediction of the topology of this transporter family utilizing a multiple sequence alignment strongly suggests the presence of a common structural motif consisting of 12 alpha-helical putative transmembrane segments and cytoplasmically located N- and C-terminal hydrophilic regions. Interestingly, recent genetic and molecular results strongly suggest that yeast amino acid permeases are integrated into the plasma membrane through a specific intracellular translocation system. Finally, speculating on their predicted structure and on amino acid sequence similarities conserved within this family of permeases reveals regions of putative importance in amino acid transporter structure, function, post-translational regulation or biogenesis. PMID- 7888173 TI - The retinoblastoma protein: more than a tumor suppressor. PMID- 7888174 TI - Vertebrate limb development. PMID- 7888175 TI - Microtubules in plant morphogenesis: role of the cortical array. PMID- 7888176 TI - Role of protein modification reactions in programming interactions between ras related GTPases and cell membranes. PMID- 7888177 TI - Structure of actin binding proteins: insights about function at atomic resolution. PMID- 7888178 TI - Receptor protein-tyrosine kinases and their signal transduction pathways. PMID- 7888179 TI - Small GTP-binding proteins and the regulation of the actin cytoskeleton. PMID- 7888180 TI - DYNEINS: molecular structure and cellular function. PMID- 7888181 TI - Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease. PMID- 7888182 TI - Structure, regulation and function of NF-kappa B. PMID- 7888183 TI - Protein serine/threonine phosphatases--new avenues for cell regulation. PMID- 7888185 TI - Tenth anniversary perspectives on AIDS. HIV: between past and future. PMID- 7888184 TI - Signal sequence recognition and protein targeting to the endoplasmic reticulum membrane. PMID- 7888186 TI - The World Health Organization Network for HIV Isolation and Characterization: summary of a pilot study. PMID- 7888188 TI - The World Health Organization Global Programme on AIDS proposal for standardization of HIV sequence nomenclature. WHO Network for HIV Isolation and Characterization. AB - The World Health Organization Global Programme on AIDS (WHO/GPA) is conducting a large-scale collaborative study of human immunodeficiency virus type 1 (HIV-1) variation, based in four potential vaccine-trial site countries: Brazil, Rwanda, Thailand, and Uganda. Through the course of this study, it was crucial to keep track of certain attributes of the samples from which the viral nucleotide sequences were derived (e.g., country of origin and viral culture characterization), so that meaningful sequence comparisons could be made. Here we describe a system developed in the context of the WHO/GPA study that summarizes such critical attributes by representing them as standardized characters directly incorporated into sequence names. This nomenclature allows linkage of clinical, phenotypic, and geographic information with molecular data. We propose that other investigators involved in human immunodeficiency virus (HIV) nucleotide sequencing efforts adopt a similar standardized sequence nomenclature to facilitate cross-study sequence comparison. HIV sequence data are being generated at an ever-increasing rate; directly coupled to this increase is our deepening understanding of biological parameters that influence or result from sequence variability. A standardized sequence nomenclature that includes relevant biological information would enable researchers to better utilize the growing body of sequence data, and enhance their ability to interpret the biological implications of their own data through facilitating comparisons with previously published work. PMID- 7888187 TI - Rapid genetic characterization of HIV type 1 strains from four World Health Organization-sponsored vaccine evaluation sites using a heteroduplex mobility assay. WHO Network for HIV Isolation and Characterization. AB - To assist in the preparation for the testing of vaccines against human immunodeficiency virus (HIV) we, as part of the World Health Organization Network for HIV Isolation and Characterization (WHO-NHIC), evaluated the genotypic variation of HIV-1 in cohorts from Brazil, Rwanda, Thailand, and Uganda. Here we report the results from a pilot study of 65 HIV-1-infected individuals. In all cases in which viral envelope gene fragments could be amplified by polymerase chain reaction, subtypes could be assigned using a heteroduplex mobility assay (HMA)1 by comparison with HIV-1 strains representing six HIV-1 envelope subtypes. All subtype classifications matched those found by envelope gene sequencing. Phylogenetic relationships were further clarified by heteroduplex formation between samples within each subtype. A relatively homogeneous subtype E virus population predominated over subtype B viruses in the sample set from Thailand. Viruses from the other countries were also limited to one or two subtypes but were more divergent within each subtype. All samples from Rwanda (13/13) and some from Uganda (3/16) were of subtype A; all Brazilian samples were of subtype B, except for one belonging to subtype C; most samples from Uganda (13/16) clustered with the subtype D. Analysis by HMA is therefore applicable for screening of HIV 1 genotypes in countries under consideration for large-scale vaccine trials. It should be generally useful when samples containing at least one variable genetic locus need to be rapidly classified by genotype and/or analyzed for epidemiological clustering. PMID- 7888189 TI - Genetic variation of HIV type 1 in four World Health Organization-sponsored vaccine evaluation sites: generation of functional envelope (glycoprotein 160) clones representative of sequence subtypes A, B, C, and E. WHO Network for HIV Isolation and Characterization. AB - As part of the WHO Network for HIV Isolation and Characterization, we PCR amplified, cloned, and sequenced gp120 and gp160 genes from 12 HIV-1 isolates collected in four WHO-sponsored vaccine evaluation sites (Brazil, Rwanda, Thailand, Uganda). Envelope clones were derived from PBMC-grown isolates obtained from asymptomatic individuals within 2 years of seroconversion. Analysis of their deduced amino acid sequences identified all but one to contain an uninterrupted open reading frame. Transient expression and biological characterization of selected gp160 constructs identified six clones to encode full length and functional envelope glycoproteins. Phylogenetic analysis of their nucleotide sequences revealed that they represent HIV-1 subtypes A, B, C, and E. Since current knowledge of HIV-1 envelope immunobiology is almost exclusively derived from subtype B viruses, these reagents should facilitate future envelope structure, function and antigenicity studies on a broader spectrum of viruses. This should assist in the design and evaluation of effective vaccines against HIV 1. PMID- 7888190 TI - Antigenic variation and serotyping of HIV type 1 from four World Health Organization-sponsored HIV vaccine sites. WHO Network for HIV Isolation and Characterization. AB - Serologic reactivities of serum or plasma from 55 HIV-1 subjects in four countries--Brazil, Rwanda, Thailand, and Uganda--were examined by V3 peptide immunoassay. Forty-seven (85.5%) of the 55 specimens tested positive to the homologous peptide. A strong correlation between serotype (i.e., pattern of serologic reactivity with a panel of peptides) and genotype was not found. However, the V3 peptide immunoassays may be useful for epidemiologic studies to trace the distinctive HIV-1 strains from different geographic regions of the world. The serology data obtained may be useful for the development of effective V3-based vaccines. PMID- 7888191 TI - Serotyping HIV type 1 by antibody binding to the V3 loop: relationship to viral genotype. WHO Network for HIV Isolation and Characterization. AB - We have investigated whether peptides representing the HIV-1 principal neutralization domain (V3) can be used as antigens in antibody-binding assays to predict the genotypes of the subjects' virus. Serum samples collected from HIV-1 infected subjects from the four WHO-sponsored vaccine evaluation sites (Uganda, Rwanda, Thailand, and Brazil) were characterized by antibody binding to a panel of synthetic V3 peptides that were derived from the consensus sequences of the V3 region of the HIV-1 subgroups according to the env phylogenetic analysis (A-E). An indirect V3 peptide-binding assay was used for primary screening, and a V3 peptide antigen-limiting ELISA was then used as a secondary assay to discriminate cross-reactivity if the screening assay was equivocal. In general, V3 peptide serology could predict HIV-1 genotypes. In sera for which the genotype of the virus was known, peptide assays could predict the correct genotype in approximately 90% of cases for genotypes A, B, C, and E; Ugandan sera of genotype D were more broadly reactive. There was considerable serological cross-reactivity between some HIV-1 genotypes, in particular between A and C, and, to a lesser extent, B and D subtypes. Owing to polymorphism at the crown of the V3 loop, an additional B peptide (B') was required to type Brazilian B genotype sera. These simple assays may help facilitate the determination and distribution of HIV-1 genotypes circulating in populations. PMID- 7888192 TI - Syncytium-inducing and non-syncytium-inducing capacity of human immunodeficiency virus type 1 subtypes other than B: phenotypic and genotypic characteristics. WHO Network for HIV Isolation and Characterization. AB - Positively charged amino acid substitutions at positions 11 and 25 within the loop of the third variable region (V3) of HIV-1 subtype B envelope have been shown to be associated with the syncytium-inducing (SI) phenotype of the virus. The present study was designed to examine SI and NSI-associated V3 mutations in HIV-1 subtypes other than B. HIV-1 RNA was isolated from 53 virus stocks and 26 homologous plasma samples from 53 recently infected individuals from Brazil, Rwanda, Thailand, and Uganda. The C2-V3 region of the viral envelope was converted to cDNA, amplified, and sequenced. Of 53 primary virus stock samples 49 were biologically phenotyped through measurement of the syncytium-inducing capacity in MT-2 cells (to differentiate between SI and NSI phenotypes). In addition, after passage of primary isolates through PHA stimulated donor PBMC, the replication capacity was determined in U937-2, CEM, MT-2, and Jurkat-tat cell lines (to differentiate rapid/high and slow/low phenotypes). According to the sequence analysis 9 (17.0%) of the viruses belonged to subtype A, 15 (28.3%) to subtype B, 1 (1.9%) to subtype C, 13 (24.5%) to subtype D, and 15 (28.3%) to subtype E. Sequence analysis of virus RNA, obtained from 26 homologous plasma samples, confirmed the homogeneity of sequence populations in plasma compared to primary virus isolates. Of the 49 viruses tested 12 had the SI phenotype, 5 were confirmed to be rapid/high, and 4 appeared to be slow/low pattern 3 replicating. Of 49, 29 had the NSI phenotype, 24 were confirmed to be slow/low pattern 1 or 2, and 3 appeared to be slow/low pattern 3 replicating. Analysis of mutations at V3 loop amino acid positions 11 and 25 revealed that 10/12 (83.3%) of the SI viruses had SI-associated V3 mutations and that 28/29 (96.6%) of the NSI viruses lacked these mutations. V3 loop heterogeneity, length polymorphism, and a high number of positively charged amino acid substitutions were most frequently found among subtype D variants. These results indicate that both the phenotypic distinction between SI and NSI viruses and the association of biological phenotype with V3 mutations is present among HIV-1 subtypes other than B. PMID- 7888193 TI - Standard conditions of virus isolation reveal biological variability of HIV type 1 in different regions of the world. WHO Network for HIV Isolation and Characterization. AB - HIV-1 isolates were obtained from four countries within the framework of the WHO Network for HIV Isolation and Characterization. The use of standard HIV isolation procedures allowed us to compare the biological properties of 126 HIV-1 isolates spanning five genetic subtypes. In primary isolation cultures, viruses from Uganda and Brazil appeared early and replicated without delay, whereas the replication of Thai viruses was delayed by several weeks. Regardless of genetic subtype or country of origin, blood samples collected more than 2 years after seroconversion yielded virus that replicated efficiently in the primary isolation cultures. None of the isolates obtained from Thailand or Rwanda replicated in cell lines, whereas 5 of the 13 Brazilian isolates and 7 of the 11 Ugandan isolates replicated and induced syncytia in MT-2 cells. As expected for virus isolates obtained early in HIV-1 infection (within 2 years of seroconversion), all viruses from Brazil, Rwanda, and Thailand showed a slow/low replicative pattern. For the Ugandan samples, the time from seroconversion was known precisely for a few of the samples and only in one case was less than 2 years. This may explain why the five viruses that were able to replicate in all cell lines, and thus classified as rapid/high, were of Ugandan origin. Viruses able to induce syncytia in MT-2 cells, also induced syncytia in PBMC. However, 8 slow/low viruses (out of 27) gave discordant results, inducing syncytia in PBMC but not in MT-2 cells. Furthermore, using syncytium induction as a marker, changes in virus populations during early in vitro passage in PBMC could be observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888194 TI - Comparative biology and pathogenesis of AIDS and hepatitis B viruses: related but different. AB - AIDS (HIV) and hepatitis B viruses are remarkably similar in their sharing of reverse transcription, in their ancestral origins and common genetic elements, and in their modes of transmission. Both are hypermutable and exist as quasispecies due primarily to errors in reverse transcription, though there is severe restriction in the replicative competence of most hepatitis B mutants. They differ in the lack of an integrase in hepatitis B virus and in their pathogenesis in the infected host. HIV survives mainly by antigenic variability, immune evasion, and impairment of immune function though viral regulatory control elements seek to restrict fatal damage to the host. Hepatitis B virus survives primarily by mutation of e antigen/core genes that directly obviates cytotoxic T cell destruction of infected liver cells, or indirectly limits destruction of infected cells through induction of anergy in the cytotoxic T cell response. Most persons infected with hepatitis B virus recover completely while recovery from HIV infection is rare if ever. Hepatitis B is highly preventable by vaccine while HIV vaccine is still seeking a meaningful immunoprophylactic target. AIDS and hepatitis B represent an extreme example, among the viruses of man, in their close similarities but distinct differences. In depth details and perspectives are presented in this review. PMID- 7888195 TI - V3-mediated heparin neutralization of HIV type 1. PMID- 7888196 TI - Reactivity of AIDS patient sera with a peptide derived from HIV type 1NY5 glycoprotein 120 V3 loop and consensus sequence of collagens. PMID- 7888197 TI - A novel method for detection and ex vivo expansion of HIV type 1-specific cytolytic T lymphocytes. AB - Studies have shown that cytolytic T lymphocyte (CTL) responses may be critical to the clearance of the early viremia in acute HIV-1 infection. It is likely that these cells play an important role in prolonging the asymptomatic phase of the infection. Although HIV-1-specific CTL activity can be detected in direct assays of freshly isolated peripheral blood lymphocytes (PBL) from some infected individuals, this method fails to detect CTL that are present at low frequency and resting, memory CTL. For these reasons, direct CTL assays on PBL from seropositive individuals may underestimate the level of CTL immunity. As part of ongoing investigations of CTL activity in HIV-1-infected individuals, we developed a novel strategy for the detection and ex vivo expansion of HIV-1 specific CTL. This technique involves selective stimulation of PBL from seropositive individuals with autologous Epstein-Barr virus (EBV)-transformed, B lymphoblastoid cell lines (B-LCL) infected with vaccinia vectors expressing various HIV-1 genes. Prior to their use for in vitro stimulation, B-LCL are treated with psoralen and UV light to inactivate vaccinia virus. After 1 week of stimulation, CTL activity in stimulated cultures is measured in a standard 51Cr release assay. This ex vivo expansion method can selectively increase the bulk culture CTL activity against env, gag and nef, even in some seropositive individuals with low CD4 counts and little evidence of HIV-1-specific CTL in assays of freshly isolated PBL. These expanded CTL are predominantly of the CD8+ phenotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888198 TI - A qualitative progression in HIV type 1 glycoprotein 120-specific cytotoxic cellular and humoral immune responses in mice receiving a DNA-based glycoprotein 120 vaccine. AB - The potential for eliciting humoral and cytotoxic T lymphocyte (CTL) responses to HIV-1 gp120 by gene gun-based DNA immunization in mice was examined. We speculated that the induction of de novo antigen production in the epidermis of BALB/c mice following particle bombardment-based gene delivery would result in both MHC class I- and class II-mediated antigen presentation for the elicitation of CTL and antibody responses, respectively. Following epidermal delivery of microgram quantities of an expression plasmid, gp120 production resulted in the appearance of MHC class I-restricted, CD8+ CTL responses. gp120-specific CTL responses peaked following a booster immunization, then declined with the appearance of gp120-specific IgG responses when additional booster immunizations were administered. This qualitative progression in the nature of gp120-specific immune responses with subsequent immunizations was paralleled by a simultaneous shift in the interferon-gamma and interleukin 4 release profiles following antigen stimulation of splenocytes in vitro. The simultaneous shifts in immune responses and cytokine release profiles indicate that the progression of antigen specific CTL and IgG responses in gp120 DNA-immunized mice may be mediated through changes in the in vivo production of cytokines, such as those associated with the Th1 and Th2 subsets of CD4+ cells. PMID- 7888199 TI - Immunogenicity of recombinant adenovirus-human immunodeficiency virus vaccines in chimpanzees following intranasal administration. AB - Recombinant adenovirus (Ad)-human immunodeficiency virus (HIV) vaccines expressing HIVIIIB Env and Gag proteins were evaluated for immunogenicity in chimpanzees following intranasal administration. When Ad7-, Ad4-, and Ad5 vectored vaccines were administered sequentially at 0, 24, and 52 weeks, respectively, to three chimpanzees, the inoculations resulted in limited virus replication in the nasopharynx, but extensive Ad-HIV replication occurred in the intestine. High-titered IgG serum antibody responses to Env and Gag that were nonneutralizing were induced following booster administration of Ad4-HIV recombinant viruses. Following the Ad5-HIV booster, low levels of neutralizing antibodies as well as V3 loop antibodies were induced in all three chimpanzees that persisted for several months. Administration of a gp160 subunit vaccine (baculovirus derived) in SAF-m 24 weeks later boosted broadly neutralizing serum antibodies that peaked within 1 month of the injection. Two additional subunit boosters 19 and 37 weeks later were progressively less effective at stimulating serum neutralizing antibody responses. Substantial local immune responses were induced in nasal, vaginal, and salivary secretions following the third Ad-HIV intranasal immunization. These responses were further boosted with the gp160 subunit vaccine, which also stimulated production of rectal antibodies. The predominant responses in all secretions tested were of the IgG isotype, although some IgA responses were also detected. Strong blastogenic responses to HIV recombinant Env and Gag proteins were induced after each immunization. PMID- 7888200 TI - Stimulation of glutathione peroxidase activity decreases HIV type 1 activation after oxidative stress. AB - Am important aspect of human immunodeficiency virus (HIV-1) infection is the regulation of its expression by nuclear factor kappa B (NF-kappa B) by redox controlled signal transduction pathways. In this study, we demonstrate that selenium supplementation can effectively increase glutathione peroxidase (GPx) activity in latently infected T lymphocytes. The Se-supplemented cells exhibited an important protection against the cytotoxic and reactivating effects of hydrogen peroxide (H2O2). Concomitantly, NF-kappa B activation by H2O2 was also decreased in Se-supplemented cells. Selenium stimulation of GPx activity also induces a protective effect against cell activation by tumor necrosis factor alpha (TNF-alpha) but less significantly by phorbol esters such as PMA. These Se mediated effects were specific because they were not found when AP-1 DNA-binding activity was studied after H2O2-induced stress. Hyperthermia was also studied because it could promote intracellular electron leakage in electron transport chains. Elevating the temperature to 42 degrees C did not induce NF-kappa B directly. Rather, it sensitized infected cells to subsequent oxidative stress by H2O2, demonstrating the importance of hyperthermia, often associated with opportunistic infections in the development of immunodeficiency. In this case, Se induced partial protection against the sensitizing effect of hyperthermia. PMID- 7888201 TI - Comparison of cellular accumulation, tissue distribution, and anti-HIV activity of free and liposomal 2',3'-dideoxycytidine. AB - We have investigated the cellular accumulation, tissue distribution, and antihuman immunodeficiency virus activity of free dideoxycytidine (ddC) and liposomal ddC (L-ddC). We have found that L-ddC was more efficiently taken up than its free form by RAW 264.7 cells (a monocyte-macrophage cell line) (p < 0.01) while a comparable uptake was seen in U937 cells (a promonocytic cell line). In the rat, L-ddC accumulated preferentially in liver and spleen when injected intravenously (p < 0.01), and mostly in spleen when given intraperitoneally (p < 0.01). In contrast, free ddC was rapidly eliminated out of the body. Liposomal ddC showed a similar anti-HIV activity in comparison with free ddC in U937 cells. Given the fact that encapsulation of ddC in liposomes does not affect its anti-HIV activity but enhances its in vitro cellular accumulation and its in vivo distribution in reticuloendothelial system (RES) tissues, we conclude that ddC in liposomal formulation is a promising anti-HIV agent with a targeted action on the RES, which is considered a reservoir for dissemination of virus to other cells, tissues, and organs. PMID- 7888202 TI - Zidovudine induces the expression of cellular resistance affecting its antiviral activity. AB - We have previously shown that multidrug-resistant cells expressing the multidrug transporter P-glycoprotein are less sensitive to the antiviral activity of AZT. Subsequently, we addressed the question whether AZT itself is able to induce cellular resistance to the drug. Indeed, CEM cells propagated in the presence of increasing concentrations of AZT become resistant to the antigrowth and antiviral activity of AZT but do not express detectable level of P-glycoprotein. Sensitivity of these cells to other compounds, such as vinblastine, vincristine, ddI, and ddC remained unchanged, indicating that, in contrast to P-glycoprotein positive cells, AZT-induced resistance is specific for AZT. Interestingly, in AZT induced resistant cells the intracellular accumulation of AZT and exogenous deoxythymidine, as well as thymidine kinase activity, are significantly reduced when compared with the parental cell line. Our findings show that AZT itself may directly induce the expression of cellular mechanisms leading to the acquisition of specific cellular resistance that can affect its antiviral activity. PMID- 7888203 TI - Calmodulin antagonists inhibit human immunodeficiency virus-induced cell fusion but not virus replication. AB - We have reported that amphipathic helical segments in the cytoplasmic domain of the HIV-1 envelope glycoproteins bind to calmodulin (CaM) with high affinity, and inhibit calmodulin-regulated proteins. To investigate the possible role of calmodulin activity in HIV-1 replication, we investigated the anti-HIV activity of various CaM antagonists--trifluoperazine and naphthalenesulfonamide W13 or W7- in HeLa T4 cells, PBMCs, and various T lymphocytic cell lines. The different CaM antagonists were found to inhibit the proliferation of the different cell types to varying extent. Also, the CaM antagonists were found to exert a greater antiproliferative effect on H9/HIV-1IIIB, as compared to uninfected H9 cells, suggesting a deficit of CaM function in HIV-infected cells. The CaM antagonists inhibited virus-induced cell fusion in HeLa T4 cells infected with a recombinant vaccinia virus expressing HIV-1 envelope proteins at threshold concentrations that do not inhibit cell proliferation. The fusion-inhibitory effects of the CaM antagonists were also observed in cocultures of HIV-infected (H9/HIV-1IIIB) and uninfected H9 cells. Under these conditions, the synthesis and surface expression of the viral glycoproteins were not affected, although the kinetics of processing of HIV envelope precursor was delayed. Virus production from both HIV-infected peripheral blood mononuclear cell (PBMC) and MT-2 cell cultures was inhibited by CaM antagonists at concentrations that were inhibitory to cell proliferation. Surprisingly, threshold concentrations of CaM antagonists that do not inhibit cell proliferation were found to enhance virus production from HIV-infected MT-2 cells, but not PBMCs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888204 TI - Potent and specific inhibition of HIV envelope-mediated cell fusion and virus binding by G quartet-forming oligonucleotide (ISIS 5320). AB - We have previously reported identification of a phosphorothioate oligonucleotide TTGGGGTT (ISIS 5320) as a potent inhibitor of HIV infection in vitro. The oligonucleotide forms a parallel-stranded, tetrameric guanosine quartet (G quartet) structure that specifically binds to the HIV envelope glycoprotein (gp120) and inhibits both cell-to-cell and virus-to-cell infection at submicromolar concentrations. In the current study we demonstrate that the tetramer inhibits the infection of laboratory-derived isolates of HIV-1 and HIV-2 in a variety of phenotypically distinct, established human cell lines and a panel of biologically diverse clinical isolates in fresh human peripheral blood lymphocytes and macrophages. The compound was also active against all drug resistant virus isolates tested. In combination with AZT, ISIS 5320 exhibits additive to slightly synergistic anti-HIV activity. Cell-based mechanism of action studies demonstrate that the compound inhibits the binding of infectious virus and virus-infected cells to uninfected target cells by binding to the cationic V3 loop of the envelope glycoprotein. The G-quartet structure is a potential candidate for use in anti-HIV chemotherapy. PMID- 7888205 TI - Further evaluation of soluble CD4 as an anti-HIV type 1 gene therapy: demonstration of protection of primary human peripheral blood lymphocytes from infection by HIV type 1. AB - We previously reported on the construction of retroviral vectors that produce a secreted form of the HIV-1 receptor, T cell antigen CD4 (Morgan et al., AIDS Res Hum Retroviruses 1990;6:183-191). In this article we test the ability of these sCD4-expressing retroviral vectors to protect human T-cell lines or primary T cells from HIV-1 infection. To demonstrate that protection from HIV-1 infection is mediated by the soluble nature of this protein, two coculture protection experiments were conducted. In these experiments, sCD4-expressing retroviral vectors were used to engineer mouse NIH 3T3 cells. In one coculture experiment the human SupT1 cell line was added directly to the culture of sCD4-producing NIH 3T3 cells, and in another experiment the two cell types were separated physically by a semipermeable membrane. In both coculture configurations, the T cell line was protected from HIV-1 challenge as measured by syncytium formation and indirect immunofluorescent assays. In addition, the SupT1 line was directly engineered with sCD4-expressing retroviral vectors and shown to be protected from HIV-1 challenge. As a prelude to further preclinical studies, we tested the ability of retroviral vectors to transduce primary human peripheral blood lymphocytes (PBLs). Conditions used to stimulate T cell growth resulted in significant shifts in the CD4/CD8 cell in favor of CD8 cells. Retroviral-mediated gene transfer under these conditions resulted in low levels of gene transfer (< 5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888206 TI - Retrovirus-mediated transfer and long-term expression of HIV type 1 tat gene in murine hematopoietic tissues. AB - Replication of the human immunodeficiency virus (HIV) is regulated tightly by the tat and rev genes. The tat gene of HIV is a potent trans-activator of virus gene expression. trans-Activation is mediated through the tat-responsive element (TAR). Tat also has been shown to affect transcription of cellular genes and to trans-activate other viral promoters. In transgenic animals, tat expression in skin was implicated in the development of lesions resembling Kaposi's sarcoma (KS). More recently, evidence has been presented that suggests that Tat might play a role in the maintenance of KS cells. To study the possible role(s) of Tat in pathogenesis and disease progression, we have developed a retroviral vector for the transfer of tat into murine bone marrow cells. We used this transduced bone marrow to repopulate recipient animals, which expressed the tat gene in peripheral blood 6 months after transplantation as determined by PCR amplification of first-strand cDNA. Analysis of the hematopoietic tissues of mice 6 months posttransplantation indicated persistence of the tat gene and its expression in thymus, lymph nodes, spleen, bone marrow, and peripheral blood. Although tat expression was sustained in all hematopoietic tissues, no gross abnormalities were observed. The presence of tat in all hematopoietic tissues strongly suggests transduction of stem or multipotential progenitor cells. PMID- 7888207 TI - Modulation of cellular gene expression of HIV type 1 infection as determined by subtractive hybridization cloning: downregulation of thymosin beta 4 in vitro and in vivo. AB - Chronic infection with HIV-1 has profound effects on host cell growth and function. We used subtractive hybridization cloning to identify genes whose expression is modulated by HIV-1 infection in the T leukemia cell line CEM. The gene encoding thymosin beta 4, a ubiquitous polypeptide associated with hematopoietic differentiation, showed two- to threefold reduced transcription in HIV-1-infected CEM cells and other HIV-1-infected T cells and macrophages in vitro. Solid-phase radioimmunoassay revealed about a threefold decrease in the level of thymosin beta 4 protein in lysates of infected cells. Northern blot analysis of RNA samples from lymphocytes of five AIDS patients reveals an up to fivefold reduction in the level of thymosin beta 4 mRNA. These results indicate that HIV-1 infection may directly influence the expression of certain physiologically important proteins. PMID- 7888208 TI - Splicing variability in HIV type 1 revealed by quantitative RNA polymerase chain reaction. AB - A quantitative RNA-polymerase chain reaction (PCR) method able to detect the majority of mRNAs produced by human immunodeficiency virus type 1 (HIV-1) was developed and used to study expression of different HIV-1 clones in human cells. Amplified mRNAs were compared to known cDNA standards. This comparison permitted the optimization of PCR conditions and eliminated the generation of artifactual PCR bands. The use of RNA and cDNA standards demonstrated that the RNA amplification is linear within the tested range and suggested that it can be used to quantitate individual mRNAs. The results demonstrate the overall conservation of splicing in different HIV-1 clones. Although, in general, splicing was conserved, extensive qualitative and quantitative variability was observed in different HIV-1 clones. This variability is likely one determinant of the biological characteristics of the different HIV-1 clones, and demonstrates a great plasticity of the HIV-1 genome. The described RNA-PCR methodology was used for the study of HIV-1 expression in unstimulated peripheral blood mononuclear cells (PBMCs) of infected individuals. In general, the same mRNAs were identified in HIV-infected cultured cell lines and in unstimulated PBMCs. Analysis of a variant band found after amplification of PBMC RNA from an HIV-infected individual revealed a new splice site for the generation of Rev/Nef-encoding mRNAs. The availability of a sensitive, rapid, and essentially quantitative method to examine the major HIV-1 mRNAs will facilitate the detailed analysis of HIV-1 expression in human cells. PMID- 7888209 TI - Presence of multiple genetic subtypes of human immunodeficiency virus type 1 proviruses in Uganda. AB - DNA sequences encoding the C2-V3 regions or the C2-V5 regions of the surface glycoprotein gp120 of the human immunodeficiency virus type 1 (HIV-1) were amplified by the polymerase chain reaction (PCR) from peripheral blood mononuclear cells obtained in 1990/1992 from 20 infected Ugandans. The PCR amplified DNA was cloned into a phagemid vector and between 1 and 12 clones from each provirus were sequenced. The Ugandan proviruses were aligned into four subtypes (A, B, C, and D) by phylogenetic analysis of consensus nucleotide sequences for the C2-V3 regions. Analysis of the deduced amino acid sequences of the C2-V3 regions by a maximum parsimony program gave a similar phylogenetic relationship. The data indicated that phylogenetic analysis of nucleotide and/or amino acid sequences from the C2-V3 regions is a reliable method of subtype determination. The consensus amino acid sequence of the subtype A and D proviruses were almost identical to those of the Albert et al. group B and group A proviruses, respectively. The deduced amino acid sequences of the C2-V5 regions of six of these proviruses showed considerable diversity both between patients and within patients. The region varied in length between 234 and 243 amino acids and included deletions and repetitions, particularly in the V4 region. PMID- 7888210 TI - Molecular epidemiology of HTLV type I in Japan: evidence for two distinct ancestral lineages with a particular geographical distribution. AB - Japan is one of the highest endemic areas of the world for human T cell leukemia lymphoma virus type I (HTLV-I). To gain new insight as to the origin of this virus in Japan and especially in the southern islands of the archipelago, we investigated the long terminal repeat (LTR) of 67 newly isolated HTLV-I proviral DNAs from peripheral blood mononuclear cells of HTLV-I-infected individuals for their restriction fragment length polymorphism (RFLP). The specimens were from Japanese living in different geographical areas (Hokkaido, Honshu, Kyushu, or the Ryukyu Islands) of Japan (59 cases) or Americans of Japanese ancestry living in Hawaii (8 cases). The analysis of the results, together with data for the 19 previously published LTR sequences, demonstrated the existence of 2 subtypes of HTLV-I in Japan. The first, which we propose to name Japanese subtype (previously named subtype III), is more frequent (67 of 86: 78%) than the second, the cosmopolitan subtype (previously named subtype II) (19 of 86: 22%). In parallel, a fragment of 413 base pairs of the U3/R region (nucleotide 22 to 434) was cloned and sequenced from 10 of the new Japanese samples. The alignment of these sequences and their comparison and phylogenetic analysis with previously published LTR HTLV-I sequences, demonstrated clearly the existence of the two distinct molecular subtypes of HTLV-I in Japan, diverging in this LTR region by about 1.6%. Furthermore, the study of the geographical distribution of the 2 subtypes among the 80 samples from patients whose place of residence in Japan was known showed an uneven distribution. While the Japanese subtype was present in all parts of Japan, the cosmopolitan subtype seemed to cluster in the southern islands of the archipelago (i.e., Kyushu and the Ryukyu Islands) as well as in immigrants from those areas who had lived in Hawaii for decades. These new molecular data raise questions and suggest hypotheses, discussed here, concerning the origin and means of dissemination of these human retrovirus subtypes in Japan. PMID- 7888211 TI - HTLV type I and HTLV type II infection among Indians and natives from Argentina. AB - Endemic foci for HTLV-II infection have been identified in several Amerindian populations. To determine HTLV-I and/or HTLV-II infection among Amerindians living in Argentina we studied 454 sera or plasmas from Indians and natives from different areas of our country. All samples were tested by the particle agglutination technique, and positive reactions were confirmed by the immunofluorescence assay (IFA). IFA titration was used to differentiate HTLV-I and HTLV-II antibodies. Twenty-three of 222 samples (10.4%) were found positive among the Tobas Indians; 22 samples were typed as HTLV-II and 1 as HTLV-I. Antibodies for HTLV-I were found in the serum and CSF of three natives from Salta with a TSP diagnosis. No positive samples were found among 96 Mapuche Indians and 133 natives from San Luis. Our results indicate that HTLV-II is endemic among the Tobas Indians. In this study, infection by these retroviruses in Argentinian Amerindians seems to have a marked geographic distribution. PMID- 7888212 TI - Early HIV type 1 strains in Thailand were not responsible for the current epidemic. PMID- 7888213 TI - Genetic variability of HIV type 1 in Kenya. PMID- 7888214 TI - Subgroup G HIV type 1 isolates from Nigeria. PMID- 7888215 TI - AIDS research: the second decade. PMID- 7888216 TI - Infection of dendritic cells with HIV type 1. PMID- 7888217 TI - HIV type 1 infection of human cortical neuronal cells: enhancement by select neuronal growth factors. AB - Neuronal cells in culture respond to neuronal growth factors by secondary cellular pathways similar to those described for activation of lymphocytes and macrophages. In HIV-1-infected T lymphocytes and in macrophages, these pathways were shown to converge on nuclear factors that bind and stimulate the HIV-1 LTR and lead to enhancement of HIV-1 expression. In the current study we have investigated whether the same mechanisms also enhance HIV-1 production by neural cells. We have demonstrated that HIV/N1T replication in HCN-1A cells, a human cortical neuronal cell line, is enhanced threefold by nerve growth factor (NGF) and by fibroblast growth factor (FGF), but not by epidermal growth (EGF) factor, or phorbol ester. HCN-1A cells also responded to HIV/N1T infection with pronounced morphological changes, indicative of a differentiation-like process. The cells diminished in size and small neurites were observed. PMID- 7888218 TI - Neural cell targets of human immunodeficiency virus type 1 in human fetal organotypic cultures. AB - Some children infected by HIV-1 demonstrate nervous system disease. Because a significant percentage of these children are believed to be infected during gestation and it is thought that HIV-1 may infect distinct glial populations, this work tested the hypothesis that different HIV-1 isolates can infect cells of the developing human fetal central nervous system (CNS). Central nervous system organotypic tissue cultures derived from human fetal brain enable the study of complex interactions between CNS cell types. Central nervous system organotypic cultures were exposed to lymphocytotropic (L-tropic) or monocytotropic (M-tropic) HIV-1 isolates and monitored for viral infection. HIV-1 gp41 and p24 antigens were detected by immunocytochemistry (ICC), HIV-1 RNA was localized in the cytoplasm of CNS cells by in situ hybridization (ISH), and viral DNA was detected by polymerase chain reaction (PCR) in HIV-1-exposed cultures. Double-label ICC identified HIV-1 antigens in both microglia and astrocytes. These results demonstrate that both L- and M-tropic isolates infect microglia and astrocytes in human fetal organotypic cultures. In addition, HIV-1 infection was detected in culture supernatants up to day 57 postinfection and at 90 days by coculture with susceptible CEM cells. HIV-1 infection of neural cells appears to be productive. This model may permit further examination of the interaction of HIV-1 with the developing human CNS and the mechanisms of AIDS-associated neuropathology. PMID- 7888219 TI - Heterokaryons formed between a rat myeloma and a mouse fibroblast are permissive for entry of HIV type 1. AB - Expression of CD4 is not sufficient for cellular susceptibility to HIV-1 entry. The majority of nonprimate cells appear to lack a factor that plays an accessory role to CD4 during virus-cell fusion. We have previously reported CD4-dependent entry in rat myeloma Y3 cells, and here we show that Y3 and CD4-expressing mouse L929 cells fuse spontaneously to produce heterokaryons susceptible to entry by HIV-1. The results suggest that a putative accessory factor necessary for entry of HIV-1 into cells is expressed by the nonprimate Y3 cell line. PMID- 7888220 TI - Non-syncytium-inducing HIV type 1 isolated from infected individuals replicates in MT-2 cells. AB - Human immunodeficiency virus type 1 (HIV-1) isolates from six infected individuals less then 4 years of age were phenotyped for their syncytium-inducing (SI) ability in MT-2 cells. Three viral isolates that induced syncytia were detected. One SI isolate was from an individual who was in disease stage P2A,B,C and two SI isolates were recovered sequentially from another individual who switched from disease stage P1B to P2F. Non-syncytium-inducing (NSI) isolates were detected in two individuals who were in stage P1B of disease, and in a third individual who was in stage P2A of disease. Three sequential isolates obtained over a 2-year period from a fourth individual who progressed from disease stage P1B to P2A,B,C and subsequently died of AIDS-related disease were also found to have the NSI phenotype. To test whether NSI isolates can replicate in the absence of syncytium formation, we analyzed NSI-infected MT-2 cells for production of viral p24 antigen and expression of viral RNA by in situ hybridization. By day 12 postinfection, 6 of 7 NSI viral isolates produced 7- to 36-fold increases in p24 antigen compared to day 6, and expressed viral RNA in 13-20% of cells. A single NSI isolate that did not replicate in MT-2 cells was obtained from an individual who was asymptomatic (stage P1B). The individual rapidly progressed to symptomatic stage P2F and two sequential SI viruses were isolated. These SI isolates replicated in MT-2 cells and induced cytopathic effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888221 TI - Dysregulation of interleukin 8, interleukin 10, and interleukin 12 release by alveolar macrophages from HIV type 1-infected subjects. AB - We examined the in vitro release of interleukin 8 (IL-8), interleukin 10 (IL-10), and interleukin 12 (IL-12) by alveolar macrophages from normal volunteers and HIV 1-infected subjects. Normal volunteers had very low levels of IL-8 and IL-10 and undetectable IL-12 in the cell-free bronchoalveolar lavage fluid (BALF). Asymptomatic HIV-1-infected subjects had elevated levels of IL-8 and IL-10 in their BALF, and HIV-1-infected subjects with nonspecific interstitial pneumonitis (NIP) or infected with Pneumocystis carinii had the highest BALF levels of IL-10 and IL-8. It was found that alveolar macrophages from asymptomatic HIV-1 subjects and from NIP subjects spontaneously released elevated IL-8, IL-10, and IL-12. However, AIDS subjects infected with P. carinii had cells that released elevated levels of IL-10 and IL-8, but low levels of IL-12. When alveolar macrophages were stimulated with Staphylococcus aureus Cowan (SAC), cells from normal volunteers responded with a considerably increased release of IL-8, IL-10, and IL-12; cells from HIV-1-infected subjects without P. carinii infection responded with a moderate increase in release of all three monokines. SAC stimulation did not enhance the release of monokines by cells from AIDS subjects with P. carinii infection, and IL-12 levels remained low. There was no strict relationship between spontaneous cytokine release and p24 HIV-1 antigen expression by alveolar macrophages. Finally, we showed that neutralizing IL-10 production by alveolar macrophages from AIDS subjects substantially increased IL-12 releasability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888222 TI - Analysis of B cell repertoire specific to the neutralizing epitopes of glycoprotein 120 in HIV-infected individuals. AB - This study describes the clonotypic analysis of neutralizing anti-gp120 antibodies elicited in HIV-infected individuals by a panel of anti-idiotype monoclonal antibodies (anti-Id MAbs). Sera from 80 HIV-infected individuals at various clinical stages of HIV-infection were tested for reactivity to 19 anti-Id MAbs in ELISA. Anti-idiotype MAbs reacted with between 0 and 26% of sera. Among the 13 idiotypes specific for anti-CD4 site antibodies, 4 were expressed in 15 to 20% of individuals, whereas 2 of 4 idiotypes specific for anti-V3 antibodies were expressed in 15 to 26% of the cases. These data suggest that each HIV-infected individuals has a diverse B cell repertoire to a given neutralizing epitope cluster and that certain clonotypes are more prevalent than others. To correlate the binding activity in ELISA with anti-gp120 specificity, the idiotype-positive antibodies (Id+ Abs) from representative serum samples were isolated by anti-Id MAb-Sepharose affinity columns. In most cases, the epitope specificity and the neutralizing properties of the isolated Id+ Abs correlated with that of anti gp120 antibodies used for the generation of anti-Id MAbs. We propose that these anti-Id MAbs may be used to identify and measure neutralizing anti-gp120 antibodies of defined specificity in the sera of HIV-infected individuals, HIV vaccinated individuals, and in HIV-infected mother-infant pairs. PMID- 7888223 TI - Molecular characterization of variable heavy and light chain regions of five HIV type 1-specific human monoclonal antibodies. AB - We have reported the generation and characterization of four HIV-1 neutralizing human monoclonal antibodies. Three antibodies recognize a conformational epitope within the CD4-binding site of HIV-1 gp120 and one recognizes a linear epitope located within the hypervariable V3 domain of gp120. In the present study we report the nucleotide sequences of the cDNAs encoding the variable regions of the heavy and light chains of these antibodies. Molecular characteristics, closet germline genes, and the putative extent of somatic mutation are presented. Two of the four heavy chain variable (VH) regions are derived from the VH1 gene family, one from the VH3 gene family, and one from the VH5 gene family. In addition, the VH chain of a previously described human monoclonal antibody, directed against HIV-1 gp41, is derived from the VH3 gene family. The degree of nucleotide variation between these five antibodies and their closest germline counterparts ranges from 4 to 12%, mainly located in the complementarity-determining regions. Significant nucleotide sequence homology with previously described germline diversity (D) genes could be found for only two of five antibody D segments. Joining (JH) gene segments utilized are JH4 or JH6. Two light chain variable (VL) regions are derived from a VK1 gene segment, one from a V kappa 4, one from a V lambda 2, and one from a lambda 6 gene segment. PMID- 7888224 TI - A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1. AB - We have established a hybridoma clone, designated 2F5, secreting a neutralizing human monoclonal antibody (MAb) specific for gp41 of human immunodeficiency virus type 1 (HIV-1). The epitope of MAb 2F5 was mapped to amino acid sequence Glu-Leu Asp-Lys-Trp-Ala on the ectodomain of gp41. In this study different in vitro test systems were used to characterize the neutralizing properties of MAb 2F5. In syncytium inhibition assays, fusion inhibition experiments, and neutralization assays on different HIV-susceptible cells (H9, U937, and peripheral blood mononuclear cells) MAb 2F5 showed broad-spectrum neutralizing capacity against HIV-1 laboratory isolates IIIB, MN, RF, and SF2. In addition, primary isolates from AIDS patients were also neutralized. PMID- 7888225 TI - Characterization of monoclonal antibodies to human immunodeficiency virus type 2 envelope glycoproteins. AB - Twelve murine monoclonal antibodies (MAbs) to human immunodeficiency virus type 2 (isolate ROD) envelope glycoproteins have been generated and characterized. Nine MAbs were specific to the external gp125 and three reacted with the transmembrane gp36. A large majority of MAbs displayed a significant affinity for the native gp140 precursor and were shown to bind to viral antigens on the surface of fixed HIV-2-infected cells. In Western blot analysis, the 12 MAbs showed varying profiles of cross-reactivity, but none of the MAbs cross-reacted with the HIV 1LAI envelope. Six MAbs reacted exclusively with the homologous HIV-2ROD isolate whereas only two MAbs displayed cross-reactivity with HIV-2ROD, HIV-2EHO, and SIVmac251. The four other MAbs cross-reacted with either HIV-2EHO or SIVmac251. Results of competitive binding assays indicated that the three anti-gp36 MAbs shared the same competition group, whereas at least eight competition groups were defined with the nine anti-gp125 MAbs. The epitopes of the three anti-gp36 and four anti-gp125 MAbs have been delineated using synthetic peptides or by immunological screening of an SIVmac251 peptide library expressed in yeast. The anti-gp36 MAbs are directed against the same domain of the transmembrane gp36 corresponding to the major antigenic determinant of HIV-2 and HIV-1. The four anti-gp125 MAbs recognize four distinct epitopes localized in the V2, V3, and C1 domains. None of the 12 MAbs displayed neutralizing activity against HIV-2ROD, including the 2 MAbs directed against the V2 and V3 domains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888227 TI - Conserved V3 loop sequences and transmission of human immunodeficiency virus type 1. AB - The third variable region (V3) of the surface glycoprotein (gp120) of envelope sequence subtype B, type 1 human immunodeficiency virus (HIV-1B), is highly variable among T cell line-adapted viruses and syncytium-inducing HIV-1-B isolates. Here we analyze the V3 region sequences from 93 individuals close to the time of seroconversion and show that the cysteine-bridged V3 loop, which also encompasses a major neutralizing determinant, is highly conserved, whereas sequences immediately surrounding the loop are similarly divergent in all HIV-1-B strains. Viruses with this conserved V3 loop have been reported to be more resistant to antibody-mediated neutralization than T cell-adapted viruses with divergent V3 sequences. We hypothesize, therefore, that on transmission from a donor to a recipient, virions inherently more resistant to neutralization by donor antibodies have a greater chance of initiating infection than those more sensitive to neutralization. This might explain the conservation of V3 early in infection and has implications for the design of HIV vaccines. PMID- 7888226 TI - Parallel evolution in the V3 region of HIV type 1 after infection of hemophiliacs from a homogeneous source. AB - To determine the genetic diversification in the highly functional V3 loop, we followed up five hemophiliacs who were infected by a homogeneous HIV-1 population from a contaminated clotting factor lot. Initially, all patients displayed identical DNA sequences in this part of the proviral env gene. Therefore, this unique outbreak allows us to investigate the biological and genetic development of a common ancestor virus in different patients. A high degree of homology is maintained in the predominant sequences from 5 until 35 months after seroconversion. Only one patient showed a remarkable diversification 3 years postinfection. However, these genetic changes in the V3 region were not associated with disease progression. Discontinuous sequence changes were observed mainly in a region downstream of the V3 loop. Two positions in particular are involved in a sequence evolution within the V3 loop leading to the same amino acids in different patients. These directed changes occurred at sites that are reported to be critical for the specificity of antibodies (position 308) and viral cytopathicity (position 324). However, the parallel evolution was associated neither with differentiation of the viral phenotype nor with progression of the disease. PMID- 7888228 TI - HIV type 1-specific cytotoxic T lymphocytes stimulate HLA class I and intercellular adhesion molecule type 1 expression and increase beta 2 microglobulin levels in vitro. AB - Besides acting in a direct manner, cytolytic HIV-1-specific CTLs release a variety of cytokines. To assess the potential role of cytokines released by these CTLs we tested the ability of soluble products secreted by HIV-1-specific CTLs to induce HLA class I and ICAM-1 expression and to raise beta 2-microglobulin (beta 2M) concentrations in cell culture. To this end, supernatants were derived from HIV-1-specific CTLs incubated with autologous B lymphoblasts presenting either the cognate HIV-1 epitope or a control peptide. Cell lines and peripheral blood mononuclear cells (PBMCs) were incubated with these supernatants for 24-48 hr. Similarly, cells were cocultured with CTLs and their targets. This study demonstrates that in parallel with lysis of their cognate target, HIV-1-specific CTLs secreted products that stimulated HLA class I and ICAM-1 expression on cell lines and PBMCs. As few as 1000 CTLs significantly induced the expression of these molecules. In addition, secreted products of HIV-specific CTLs enhanced beta 2M release by PBMCs and Jurkat cells. These effects were mediated primarily by IFN-gamma and suggest that HIV-specific CTLs may contribute to increased HLA class I expression in infected tissue and elevated ICAM-1 and beta 2M concentrations in serum and cerebrospinal fluid of infected individuals. PMID- 7888229 TI - Ultraviolet-light-inactivated Cas-Br-M murine leukemia virus induces a protective CD8+ cytotoxic T lymphocyte response in newborn mice. AB - Newborn NFS/N mice are susceptible to the neurological disease induced by infection with Cas-Br-M murine leukemia virus (Cas), and do not develop a protective cytotoxic T cell (CTL)-mediated response to Cas infection. Here we demonstrate that whole UV light-inactivated Cas (UV-Cas), inoculated in newborn NFS/N mice, induced a strong, Cas-specific CTL response detectable 2 weeks postinoculation and persisting in vivo for > or = 36 weeks. The magnitude of the UV-Cas-induced splenic CTL response, mediated by CD8+ T cells, inversely correlated with the level of proviral cas env sequences detectable in the spleen of the UV-Cas-inoculated mice, as revealed by PCR amplification of tissue DNA. The transfer of UV-Cas-primed splenocytes, with Cas-specific CTL activity, protected 100% of recipient newborn mice from the development of neurological disease induced by infection with live Cas, for more than 28 weeks, and reduced the level of viral replication in the recipients. PMID- 7888230 TI - Absence of recoverable infectious virus and unique immune responses in an asymptomatic HIV+ long-term survivor. AB - We have studied a woman with transfusion-acquired HIV who appears to have contained infectious virus to consistently undetectable levels over a 13-year period without antiviral treatment. She received the infected transfusion for intra- and postpartum blood loss immediately after delivery of her second child in 1981. She had no acute febrile syndrome and has never had HIV-associated clinical signs or symptoms in the 13 years since infection. She was first tested and found positive for HIV antibodies in 1985, and the infected blood donor was diagnosed with AIDS in 1986 and died of AIDS-related complications in 1989. Two other recipients of packed erythrocytes from this donor (in 1980 and 1982) also became infected and were subsequently diagnosed with AIDS. Between January 1986 and April 1994, in the setting of continuous and unambiguous Western blot HIV specific antibodies and intermittently positive low-level HIV DNA signal after polymerase chain reaction (PCR) amplification, more than 30 separate cell cocultures performed in several independent laboratories failed to yield evidence of infectious virus, despite special efforts to induce and detect HIV replication. Immunologically, a strong in vitro proliferative response to HIV envelope proteins also distinguished this subject from other asymptomatic HIV+ individuals. PMID- 7888231 TI - Studies of high doses of a human immunodeficiency virus type 1 recombinant glycoprotein 160 candidate vaccine in HIV type 1-seronegative humans. The AIDS Vaccine Clinical Trials Network. AB - We examined the safety and immunogenicity of a baculovirus-derived recombinant HIV-1 envelope glycoprotein vaccine candidate, rgp160 (VaxSyn; MicroGeneSys, Meriden, CT), administered at doses of 160 or 640 micrograms to 56 healthy, HIV-1 seronegative adults, in a randomized, double-blind, placebo-controlled study. Immunizations were given intramuscularly at 0, 1, 6, and 12 months. Both doses were generally well tolerated, although self-limited local reactions were frequent. No other clinical or laboratory toxicities were noted, and no effects on CD4 or CD8 lymphocyte counts or percentages were noted. Serum antibody responses to HIV proteins were detected by Western blot (WB) in 19 of 20 and in 19 of 19 recipients of four doses of 160 and 640 micrograms, respectively. Western blot responses developed more rapidly in the 640-micrograms group. High rates of EIA antibody responses to HIV-1 lysate were also present in both groups, and developed more rapidly in the 640-micrograms group. Enzyme immunoassay antibody responses to the immunogen (rgp160) were also frequent, but were infrequent to V3 to gp41 peptides. Neutralizing antibodies against the homologous HIV-1 LAI isolate were seen in 3 of 20 subjects (GMT = 11) who received four doses of 160 micrograms, and in 10 of 19 subjects who received four doses of 640 micrograms (GMT = 32). Fusion inhibiting antibody was not detected. CD4 blocking activity was seen in 3 of 19 subjects who received four doses of 640 micrograms. Complement-mediated antibody-dependent enhancement was found in sera from 11 of 19 volunteers in the 640-micrograms group. Lymphocyte proliferative responses to the immunogen were detected in 4 of 4 subjects tested, but no cytotoxic T cell activity was noted in 11 subjects. Administration of the 640-micrograms dose of this rgp160 vaccine candidate relative to the lower doses was associated with increased immunogenicity, including higher rates of homologous neutralizing antibody responses, although at low titer. PMID- 7888232 TI - Comparison of the sensitivities of primary isolates of HIV type 2 and HIV type 1 to antiviral drugs and drug combinations. AB - The sensitivity of primary isolates of HIV-2 to the antiretroviral drugs 3'-azido 3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (ddI), and 3'-fluoro-3' deoxythymidine (FLT) was measured in vitro in PBMCs and compared to that of primary isolates of HIV-1. HIV-2 isolates showed a similar sensitivity to the drugs compared to HIV-1 isolates. Both the relative and the absolute potencies of the three drugs were similar for inhibition of HIV-1 or HIV-2 replication. The effect of combinations of the antiviral drugs was also studied. The combinations of AZT plus FLT, AZT plus ddI, and FLT plus ddI showed synergistic inhibition of three primary HIV-2 isolates, similar to that previously shown for primary HIV-1 isolates. These results indicate that primary isolates of HIV-2 from untreated persons show a level of sensitivity to antiviral nucleoside analogs similar to that shown by HIV-1 isolates, and are also synergistically inhibited by drug combinations shown to be synergistic against HIV-1. Therapeutic regimes with nucleoside analogs used clinically against HIV-1 infection may therefore also be similarly useful against infection with HIV-2. PMID- 7888233 TI - Early stages of feline immunodeficiency virus infection in lymph nodes and spleen. AB - Analysis of the early stages of infection within the lymphoid organs is crucial for the understanding of the physiopathology of HIV infection. Such analysis can only be performed using animal models. Cats were infected with two strains of FIV and killed at regular intervals for a classic pathologic study along with a quantification of the viral load by in situ hybridization in the spleen and the lymph nodes. The pathological study showed a persistent follicular reaction, which peaked 15 days postinoculation (p.i.). The in situ hybridization study showed two types of labeling. The first was spot labeling corresponding to cells actively replicating the virus. The second consisted of a more diffuse labeling linked to the follicular dendritic cells (FDCs) demonstrating by colocalization of virus detected by in situ hybridization associated with the FDCs, specifically labeled by immunohistochemistry. The number of productive cells is few and identical for the two viruses tested. Despite a slight peak at 15 days p.i., the number of infected cells persists while slightly decreasing over time. The FDC virus load appears jointly with the appearance of antibody and remains permanent until the end of the study at 3 years p.i. These results show that in the FIV model, there is a chronic permanent infection in the lymphoid organs. Furthermore, as compared with the SIV-macaque model, there is a correlation between the low number of infected cells detected in these organs in the early phase and the extended length of the asymptomatic period, which contrasts with the high level of the FDC virus load lasting during the same period. PMID- 7888234 TI - Superinfection of cats with feline immunodeficiency virus subtypes A and B. AB - The ability of feline immunodeficiency virus (FIV) isolates from subtypes A and B to superinfect cats and cell cultures was tested. Three specific pathogen-free (SPF) cats were first inoculated with 10 ID50 of subtype B virus (FIVBang) and 30 weeks later inoculated with 100 ID50 of subtype A virus (FIVPet). On the basis of subtype-specific PCR analysis, both FIV subtypes were detected in the peripheral blood lymphocytes (PBLs) of two of three cats from 9 to 30 weeks following the second inoculation. Only the first virus was detected in the bone marrow (BM) cells of these two cats until 30 weeks following the second inoculation, at which time the second virus was finally detected in their BM cells. Both cats developed significant virus-neutralizing (VN) antibodies to the second virus by 15 weeks following the second inoculation; but only one cat had high VN titers to the first virus, which remained at the same level even after the second inoculation. The two control cats inoculated with only the second virus developed VN titers specifically to the second virus and were consistently PCR positive for the virus in PBLs and BM cells starting 9 weeks postinoculation. Thus a delay in BM infection with the second virus was observed in the two superinfected cats. In contrast, one of three cats had neither VN antibodies to the second virus nor PCR signal of the second virus in its PBLs, BM, and lymph node throughout the 30 weeks of study and it appeared to be resistant to superinfection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888236 TI - The long terminal repeat of the human immunodeficiency virus type 1 GER isolate shows a duplication of the TAR region. PMID- 7888235 TI - Presence of human T lymphotropic virus types I and II in Ghana, west Africa. AB - Until recently, HTLV-I was considered to be an Old World virus and HTLV-II was thought to be endemic in the Americas. However, the presence of HTLV-II among Pygmies and other populations of Africa has raised doubts as to whether HTLV-II is primarily a New World virus. The large serosurveys conducted in the urban and rural areas of southern Ghana have identified a 1-2% prevalence for HTLV-I/II. To define the HTLV type, we have used a Western blot assay (HTLV-2.3 blot) that allows simultaneous confirmation and differentiation between HTLVs. Samples (n = 139) were chosen on the basis of previous reactivity with either an enzyme immune assay or r21e-spiked WB results. The WB 2.3 analysis of these specimens identified 55 (40%) to be HTLV positive, 70 (50%) to be HTLV indeterminant, and 14 (10%) to be HTLV negative for HTLV. HTLV seroindeterminant patterns ranged from both gag and env (14 were r21+, p24+, and/or p19+ [all were RIPA negative]) to gag only (21 were p24+/p19+, 16 were p19+, and 7 were p24+), and env only (8 were r21+ and 4 were rgp46+) reactivities. Of the 55 HTLV-positive specimens, 41 were typed as HTLV-I, 9 were HTLV-II, and 5 could not be typed (HTLV-I/II). Of the nine HTLV-II-positive specimens, three were from patients with Burkitt's lymphoma and six were from healthy individuals (two pregnant women) with no obvious risk factors for HTLV-II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888237 TI - vpu and env sequence variability of HIV-1 isolates from Tanzania. PMID- 7888238 TI - Sequence analysis of the glycoprotein 120 coding region of a new HIV type 1 subtype A strain (HIV-1IbNg) from Nigeria. PMID- 7888239 TI - Conceptualizations of decision making in nursing: analytic models and "knowing the patient". AB - Most studies of clinical decision making in nursing have been guided by analytic theories, such as information-processing and decision-analysis theories. Recently, some investigators have used naturalistic methods and have identified "knowing the patient" as relevant to clinical judgment. The author discusses two lines of inquiry and offers possible explanations for differences between the two conceptualizations of clinical decision making. Insights for future research are proposed. PMID- 7888240 TI - You make the diagnosis: a plan for long-term care based on the nursing theory of modeling and role-modeling. PMID- 7888242 TI - On nurturing nurses. PMID- 7888241 TI - Components of written nursing diagnostic statements. AB - The author examined whether nurses in an acute care setting use nursing diagnoses and correctly construct nursing diagnostic statements. Using a retrospective chart audit of a 237-bed acute care hospital, the author examined 150 diagnostic statements written by registered nurses. The Ziegler Criteria for Evaluating the Quality of the Nursing Process (ZCEQNP) was used to measure the components of the nursing diagnostic statements. The ZCEQNP is composed of 12 specific criteria that judge a diagnosis in general, and the response and etiology components individually. The findings revealed that only 4 of 150 diagnostic statements met all 12 criteria. The etiology component of the diagnostic statements was the least accurate: Only 16 out of 150 diagnostic statements met all of the etiology criteria. The findings indicate that nurses do not accurately compose nursing diagnostic statements. Implications and strategies for improvement are suggested. PMID- 7888244 TI - Nursing diagnosis internationally. PMID- 7888243 TI - Integrating nursing diagnosis for population groups within community health nursing practice. AB - Conflicting views exist about the utility of nursing diagnosis in community health nursing, particularly in relation to its use with population groups. Until recently, this application of nursing diagnosis received limited consideration by the North American Nursing Diagnosis Association. As a result, discussion is needed regarding the ways in which use of nursing diagnosis with population groups in community settings may be different from the use of nursing diagnosis with individuals. In this article several distinctive characteristics of the use of nursing diagnosis for health promotion with various population groups are addressed. Thoughtful consideration of these distinctive characteristics can provide a foundation for effective use of nursing diagnosis with population groups in community settings. PMID- 7888245 TI - Nurse practitioners' use of nursing diagnosis. AB - The role of the nurse practitioner (NP) represents a unique blend of nursing and medical functions. Few studies exist that address the nursing component of the NP role and no literature is available to document the extent to which nurse practitioners utilize nursing diagnoses in their clinical practice. Thus, the author reports findings of a study that sought to describe the use of nursing diagnosis in current NP practice and to identify advantages and barriers to the use of nursing diagnoses by NPs. Fifteen percent of nurses surveyed used nursing diagnoses in their practice. The diagnoses most commonly used reflected attention to clients' lifestyles and daily living problems. PMID- 7888246 TI - Dynamic cardiomyoplasty for heart failure. PMID- 7888247 TI - Increased monocyte tissue factor expression in coronary disease. AB - OBJECTIVE: To investigate whether monocyte expression of tissue factor is increased in patients with acute coronary syndromes and chronic stable angina. DESIGN: Cross sectional study of monocyte tissue factor expression in patients with ischaemic heart disease and control subjects. BACKGROUND: Unstable angina and myocardial infarction are associated with enhanced mononuclear cell procoagulant activity. Procoagulant activity of blood monocytes is principally mediated by tissue factor expression. Tissue factor initiates the coagulation cascade and monocyte tissue factor expression may therefore be increased in these syndromes. METHODS: Monocyte tissue factor expression was measured cytometrically in whole blood flow using a polyclonal rabbit antihuman tissue factor antibody. PATIENTS: 30 patients with acute myocardial infarction, 17 with unstable angina, 13 with chronic stable angina, and 11 normal control subjects. RESULTS: Increased proportions of monocytes expressing tissue factor (> 2.5%) were found in none of 11 (0%) normal subjects, five 13 (38%) patients with stable angina, 11 of 17 (64%) patients with unstable angina, and 16 of 30 (53%) patients with myocardial infarction (2P = 0.006). Blood from all subjects showed similar monocyte tissue factor expression similar monocyte tissue factor expression (46.1 (15.1)%) after lipopolysaccharide stimulation. CONCLUSION: Hypercoagulability associated with acute myocardial infarction, unstable angina, and chronic stable angina may be induced by tissue factor expressed on circulating monocytes. PMID- 7888248 TI - Asymptomatic ischaemia during daily life in stable coronary artery disease: relevant or redundant? PMID- 7888249 TI - Issues in cardiac pacing; can agism be justified? PMID- 7888250 TI - Detection of left ventricular dysfunction after myocardial infarction: comparison of clinical, echocardiographic, and neurohormonal methods. PMID- 7888251 TI - Will serum enzymes and other proteins find a clinical application in the early diagnosis of myocardial infarction? PMID- 7888252 TI - Haemodynamic deterioration after treatment with adenosine. PMID- 7888253 TI - Near miss paradoxical embolism. PMID- 7888254 TI - Inhibition of superoxide production in human neutrophils by combinations of heparin and thrombolytic agents. AB - OBJECTIVE: To investigate the effect of heparin and thrombolytic agents on superoxide generation by human neutrophils, as inhibition of superoxide production may have a role in reducing ischaemia and reperfusion injury. METHODS: Neutrophil superoxide production stimulated by phorbol myristate acetate (PMA), opsonised zymosan, or formyl methionyl leucyl phenylalanine (FMLP) was measured as the superoxide dismutase inhibitable reduction of acetyl ferricytochrome c by a microtitre plate technique. RESULTS: Heparin, at concentrations of 0.5-500 U/ml, caused a gradual inhibition of superoxide production stimulated by PMA, opsonised zymosan, or FMLP. Tissue plasminogen activator was more potent than heparin in inhibiting superoxide production induced by opsonised zymosan or FMLP, but it did not affect the activity stimulated by PMA. Streptokinase or urokinase had no effect on superoxide production. When heparin was used in combination with tissue plasminogen activator, streptokinase, or urokinase at their therapeutic concentrations there was a significant inhibition of superoxide generation (70%, 30%, and 25%, respectively). The therapeutic concentrations of tissue plasminogen activator alone caused a reduction of 40% of neutrophil superoxide production. When tissue plasminogen activator and streptokinase were both added to neutrophils, however, a synergistic inhibition of 80% was achieved. CONCLUSIONS: The inhibition of super oxide generation by these drug combinations may explain the limited inflammatory response and reduction of reperfusion injury observed in patients receiving thrombolytic treatment. PMID- 7888255 TI - Infections after cardioverter-defibrillator implantation: observations in 335 patients over 10 years. AB - OBJECTIVE: To determine the incidence of infection after implantation of a cardioverter-defibrillator and the management of this complication. SUBJECTS: 335 consecutive patients who had a cardioverter-defibrillator implanted between January 1984 and December 1993. MAIN OUTCOME MEASURES: Incidence of infection within the first month after implantation (early infection) and after the first month (late infection). RESULTS: Infections associated with cardioverter defibrillator devices occurred in 13 patients (3.9%) during a mean follow up of 22 (11) months. All patients had general signs of inflammation, fever (> 37.5 degrees C), and leucocytosis (> 10,000/ml) with or without purulent drainage. Five patients (38%) had infections during the first implantation, whereas eight patients (62%) had infections after replacement of the pulse generator. Early infection was observed in four patients (31%) and late infection in nine (69%). Incidence of infection was higher in patients who underwent epicardial cardioverter-defibrillator implantation (12/207 patients, 5.8%) than in those who received nonthoracotomy lead systems (1/125 patients, 0.8%) (P < 0.05). Infections were caused by staphyloccocus in 10 patients, pseudomonas in two patients, and streptococcus in one patient. The whole device had to be removed in all patients. During a mean follow up of 39 (29) months seven patients died: six of congestive heart failure and one of myocardial reinfarction. CONCLUSIONS: Infection, one of the most serious complications after cardioverter-defibrillator implantation, is associated with increased morbidity and mortality. When infection occurs the system must be removed to avoid a fatal outcome. PMID- 7888256 TI - Vasoconstrictor peptides and cold intolerance in patients with stable angina pectoris. AB - BACKGROUND: The exact mechanism that explains the phenomenon of cold intolerance in patients with angina remains controversial. Although the response to the effects of a cold environment has been examined in these patients, their response to cold air inhalation has produced conflicting results. In addition, the possible role of vasoactive peptides in the pathophysiology has not been explored. OBJECTIVES: The aims of this study were to examine the response of patients with stable angina to the effects of cold air inhalation during exercise testing, and to investigate the possible role played by the vasoconstrictor peptides endothelin-1 (ET-1) and angiotensin-II (AT-II) in the pathophysiology. METHODS: In a randomised order, 12 men with stable angina, whose medication had been stopped, underwent two separate symptom limited treadmill exercise tests. At one visit the patients exercised while breathing room air and at the other visit they exercised while breathing cold air from a specially adapted freezer. Serial peripheral venous blood samples were taken for ET-1 and AT-II estimations during each visit. RESULTS: Cold air inhalation resulted in a significant reduction in the mean time to angina (232.7 (20.4) s v 274.1 (26.9) s, P = 0.04) and the mean total exercise time (299.5 (27.0) s v 350.3 (23.9) s, P = 0.008), but no significant change in the time to 1 mm ST depression (223.3 (29.0) s v 241.3 (29.2) s, P = 0.25). There was no significant difference between the rate pressure products at the onset of angina (P = 0.13) and the time to 1 mm ST depression (P = 0.85), but at peak exercise the rate-pressure product was significantly lower in patients breathing cold air as opposed to room air (P = 0.049). There was an equivalent significant decrease in ET-1 concentrations at peak exercise compared with that at rest at both visits (room air 5.0 (0.7) pmol/l v 4.3 (0.7) pmol/l, P = 0.03; cold air 4.4 (0.6) pmol/l v 3.8 (0.5) pmol/l, P = 0.02). There was a significant increase in AT-II concentrations 10 min after peak exercise in patients breathing room air (39.2 (6.1) pmol/l v 32.1 (4.8) pmol/l, P = 0.01) which was not repeated during cold air inhalation (36.6 (3.4) pmol/l v 28.3 (3.4) pmol/l, P = 0.07). CONCLUSIONS: Cold air inhalation in patients with stable angina results in an earlier onset of angina and a reduction in exercise capacity. Both peripheral and central reflex mechanisms appear to contribute to the phenomenon of cold intolerance. Peripheral ET-1 and AT-II do not appear to play a significant role in the pathophysiology. PMID- 7888257 TI - QT dispersion and components of the QT interval in ischaemia and infarction. AB - OBJECTIVE: To evaluate changes in QT dispersion and components of the QT interval in patients admitted with unstable angina and acute myocardial infarction and to study the dynamics of these changes in patients with infarction. METHODS: Prospective study recording electrocardiograms at 50 mm/s in patients admitted with typical cardiac chest pain. Subsequent confirmation of acute myocardial infarction according to standard criteria. Single blind analysis for QT dispersion and QT components using a digitiser and simple computer program. Results are expressed as native QT dispersion, QTc dispersion, and the QT dispersion ratio defined as QT dispersion divided by cycle length and expressed as a percentage. RESULTS: QT dispersion, QTc dispersion, and QT dispersion ratio were all higher in patients with acute myocardial infarction than in those with unstable angina (mean (SD) 66 (18) ms, 75 (26) ms1/2, and 8.1 (2.4)% compared with 38 (13) ms, 39 (13) ms1/2, and 4.5 (1.7) % respectively). Dynamic changes in QTc dispersion were seen after acute infarction with significant differences in the QT components occurring between the different patient groups. Levels of QT dispersion (87 (15) ms), QTc dispersion (105 (17) ms1/2), and QT dispersion ratio (11.7 (0.8)%) in the four patients with ventricular fibrillation were significantly higher. Use of QT dispersion ratio gave a narrower confidence interval. CONCLUSION: QT dispersion is increased after myocardial infarction and levels are higher in patients with ventricular fibrillation. The changes in QT dispersion are dynamic and may reflect the changing pattern of underlying ventricular recovery of ventricular excitability, which is profoundly disturbed in the earliest phase of acute infarction. Expressing QT dispersion as a percentage of cycle length (QT dispersion ratio) rather than using standard rate correction may be superior in identifying patients who develop ventricular fibrillation. PMID- 7888258 TI - Increased dispersion of refractoriness in the absence of QT prolongation in patients with mitral valve prolapse and ventricular arrhythmias. AB - BACKGROUND: The mechanism responsible for the reported high incidence of ventricular arrhythmias in mitral valve prolapse is not clear. Electrocardiographic studies show an increased occurrence of repolarisation abnormalities on the 12 lead surface electrocardiogram, indicating regional differences in ventricular recovery. The purpose of this study was to investigate whether dispersion of refractoriness was an arrhythmogenic mechanism. METHODS: QT dispersion was measured in 32 patients with echocardiographically documented mitral valve prolapse and ventricular arrhythmias on 24 hour Holter recordings. QT dispersion was defined as the difference between the maximum and minimum average QT interval in any of the 12 leads of the surface electrocardiogram. QT dispersion corrected for heart rate was calculated by Bazett's formula. The results were compared with the data from 32 matched controls without a history of cardiac disease. Patients taking drugs that influence the QT interval and patients with a QRS duration > 120 ms were excluded. RESULTS: QT dispersion was greater in patients with mitral valve prolapse than in matched controls (60 (20) v 39 (11 ms) respectively, P < or = 0.001) as was corrected QT (64 (20 ms) v 43 (12 ms) respectively, P < or = 0.001). There was no significant difference in minimum or maximum QT intervals between the two groups. CONCLUSIONS: QT dispersion on the 12 lead surface electrocardiogram was greater in patients with mitral valve prolapse with ventricular arrhythmias than in normal controls, but the maximum QT interval was not increased. The results accord with the hypothesis that regional shortening and lengthening of repolarisation times in patients with mitral valve prolapse may account for the increased dispersion of refractoriness. PMID- 7888259 TI - Cholesterol lowering does have a role in secondary prevention. PMID- 7888260 TI - Activation and inhibition of the endogenous opioid system in human heart failure. AB - BACKGROUND: In a canine model of congestive heart failure beta endorphin concentrations were high and opioid receptor antagonists exerted beneficial haemodynamic effects. In humans previous studies have suggested that opioid peptides may modify the perception of breathlessness and fatigue in heart failure. METHODS: Plasma concentrations of beta endorphin were measured in patients with acute and chronic heart failure and cardiogenic shock. A subgroup of eight patients with New York Heart Association (NYHA) class III-IV heart failure was assessed for acute haemodynamic effects of naloxone, an opioid receptor antagonist. A separate group of 10 patients with class II-III heart failure, was randomised to a double blind placebo controlled study of the effects of intravenous naloxone on cardiopulmonary exercise performance. RESULTS: Plasma concentrations of beta endorphin were usually normal in patients with chronic heart failure and did not correlate with severity as assessed by NYHA class. In 29% of patients with acute heart failure and 71% of those with cardiogenic shock beta endorphin concentrations were high. The median concentration in the cardiogenic shock group was significantly higher than in either of the two heart failure groups and there was some evidence of a relation between beta endorphin concentrations and survival. At the doses tested, naloxone was unable to modify systemic haemodynamics, exercise performance, or symptoms in patients with chronic congestive heart failure. CONCLUSIONS: Circulating concentrations of beta endorphin are usually normal in patients with chronic congestive heart failure. Inhibition of the endogenous opioid system is unlikely to have therapeutic potential in heart failure. PMID- 7888261 TI - Morphological, haemodynamic, and clinical variables as predictors for management of isolated ventricular septal defect. AB - OBJECTIVE: To assess the predictive impact of morphological, haemodynamic, and clinical variables in the management of patients with isolated ventricular septal defect. DESIGN: Retrospective analysis of variables by a sophisticated database management system. PATIENTS AND METHODS: 263 consecutive patients with isolated ventricular septal defect diagnosed by echocardiography. The morphological type and haemodynamic character of the ventricular septal defect was characterised in each patient. In addition, variables were introduced to represent the need for diuretics, growth, and potential delay in growth. In 43 patients (16.3%) the ventricular septal defect was closed surgically; 220 patients (83.7%) were managed conservatively and spontaneous closure of the ventricular septal defect occurred in 65 (29.5%). There were no deaths. RESULTS: All patients managed surgically had non-restrictive defects and were operated on during the first year of life. A few patients with non-restrictive defects were managed conservatively. The two groups differed significantly only with respect to mean growth delay (0.65 (0.27) v 0.9 (0.21), P < 0.001). Only the morphology of the ventricular septal defect significantly (P < 0.001) influenced the probability of closure. CONCLUSIONS: Findings imply that early surgical closure of ventricular septal defect is indicated in patients with non-restrictive ventricular septal defect and severe growth delay. Other patients should be managed conservatively. In these patients the morphological type of the defect determines the probability of spontaneous closure and provides an estimate of the period over which decreased in size or closure can be expected. PMID- 7888263 TI - Use of the implantable defibrillator. PMID- 7888262 TI - Doppler reconstruction of left ventricular pressure from functional mitral regurgitation: potential importance of varying orifice geometry. AB - OBJECTIVE: To assess the left ventricular pressure pulse, in particular its time course, reconstructed from the continuous wave Doppler signal of functional mitral regurgitation using the simplified Bernoulli equation. DESIGN: Prospective study with simultaneously recorded high fidelity left ventricular pressure and continuous wave Doppler traces of functional mitral regurgitation, along with indirect left atrial pressure, electrocardiograms, and phonocardiograms. SETTING: Tertiary referral cardiac centre. PATIENTS: 9 patients (age 60 (17) years) were studied immediately before or 1-20 h after routine cardiac surgery. RESULTS: 104 cardiac cycles were analysed. There were no consistent differences between directly measured and reconstructed pressures in the time intervals from Q to + dP/dt (mean (SD) 125 (35) v 130 (35) ms and from Q to -dP/dt (389 (30) v 387 (28) ms or from Q to maximum pressure (267 (40) v 270 (40) ms, all P = NS). The time from Q to the onset of pressure rise (67 (30) v 64 (30) ms, P < 0.01) and the duration of total left ventricular systole (404 (50) v 408 (50) ms, P < 0.01) measured by the two methods were effectively identical, though the small difference was consistent enough to be statistically significant. The calculated peak pressure drop between the left ventricle and the left atrium (45-100 mm Hg) significantly underestimated left ventricular pressure (72-150 mm Hg; 70 (11) v 105 (15) mm Hg, P < 0.01) even if mean left atrial pressure (14 (4.0) mm Hg) was taken into account. Compared with those directly derived from left ventricular pressure, values of pressure measured at + dP/dt (26 (6.5) v 53 (10) mm Hg, P < 0.01) and -dP/dt (30 (8.0) v 60 (10) mm Hg, P < 0.01), and those of the rates of increase (675 (155) v 815 (155) mm Hg/s, P < 0.01) and fall (610 (145) v 845 (175) mm Hg, P < 0.01) were all significantly underestimated by Doppler. The underestimation in peak rates of pressure change could not entirely be explained by a scaling effect of absolute pressure. To investigate interrelations between the two methods throughout the cardiac cycle, reconstructed left ventricular pressure was plotted against the direct record. The plots confirmed that the reconstructed pressure was always less than directly measured pressure, the relative degree of underestimation falling as the pressure rose. This was not the effect of acceleration but probably reflects changing geometry of the regurgitant orifice. CONCLUSION: The continuous wave Doppler trace of functional mitral regurgitation is suitable for studying the timing of overall mechanical events and normalised rates of change of pressure in the left ventricle. Estimates of atrioventricular pressure drop by this method and particularly its absolute rates of change seem to be less reliable. PMID- 7888264 TI - Impairment of diastolic function during short-term anthracycline chemotherapy. AB - OBJECTIVE: To assess the early changes in left ventricular diastolic and systolic function due to anthracycline treatment. DESIGN: A prospective study of cardiac function by radionuclide angiography in adults before and one month after the end of anthracycline treatment. PATIENTS: 60 patients without cardiac disease treated with chemotherapy containing anthracycline. METHODS: Cardiac function was assessed by radionuclide measurement throughout treatment. Ejection fraction, peak ejection rate, time to peak ejection rate, filling rate, and time to peak filling rate were measured before and after treatment. To normalise radionuclide measurements of the left ventricular diastolic function the ratio of the filling rate to the ejection fraction and the ratio of the filling rate to the peak ejection rate were calculated. RESULTS: No patient developed symptomatic congestive cardiac failure. The ejection fraction decreased from 58% (5%) to 55% (6%) (P < 0.001), the peak ejection rate fell from 2.99 (0.41) to 2.77 (0.41) of the end diastolic volume per second (P < 0.001), and the peak filling rate from 2.71 (0.47) to 2.55 (0.44) of the end diastolic volume per second (P < 0.01) after treatment. No difference was observed in the normalised ratios. CONCLUSIONS: This report shows simultaneous impairment of left ventricular systolic and diastolic radionuclide parameters. The absence of variation in normalised measurements suggests similar changes in ejection fraction, peak ejection rate, and peak filling rate throughout treatment. PMID- 7888265 TI - Continuous low dose inhaled nitric oxide for treatment of severe pulmonary hypertension after cardiac surgery in paediatric patients. AB - OBJECTIVE: To assess the effect of inhaled nitric oxide (NO) on severe postoperative pulmonary hypertension in children after surgical repair of a congenital heart defect. DESIGN: A pilot study of NO administration to 7 consecutive children who required adrenergic support and in whom postoperative mean pulmonary artery pressure was more than two thirds of mean systemic pressure and persisted despite alkalotic hyperventilation. SETTING: Routine care after cardiac surgery for congenital heart disease in a multidisciplinary paediatric intensive care unit. METHODS: Continuous inhalation of NO, initially at 15 ppm. Therefore, daily attempts at complete weaning or at reducing NO to the lowest effective dose. RESULTS: In 6 of the 7 children NO inhalation selectively decreased mean (SD) pulmonary artery pressure from 51 (12) to 31 (9) mm Hg (P < 0.05) while mean systemic arterial pressure was unchanged (68 (10) v 71 (7) mm Hg) (NS) and the arteriovenous difference in oxygen content decreased from 6.7 (0.9) to 4.8 (0.8) vol% (P < 0.05). Concomitantly PaO2 increased from 158 (98) to 231 (79) mm Hg) (P < 0.05). The seventh child showed no response to NO up to 80 ppm, could not be weaned from cardiopulmonary bypass, and died in the operating room. In responders, attempts at early weaning from NO inhalation always failed and NO at concentrations of less than 10 ppm was continuously administered for a median of 9.5 days (range 4 to 16 days) until complete weaning was possible from a mean dose of 3.9 (2.9) ppm. Methaemoglobinaemia remained below 2% and nitrogen dioxide concentrations usually ranged from 0.1 to 0.2 ppm. One child later died and five were discharged. A few months after surgery Doppler echocardiography (and catheterisation in one) showed evidence of regression of pulmonary hypertension in all 5. CONCLUSIONS: Inhalation of NO reduced pulmonary artery pressure in children with severe pulmonary hypertension after cardiac surgery and this effect was maintained over several days at concentrations carrying little risk of toxicity. PMID- 7888266 TI - Positron emission tomography with oxygen-15 of stunned myocardium caused by coronary artery vasospasm after recovery. AB - Stunned myocardium is often observed after unstable angina, myocardial infarction, thrombolysis, angioplasty, and bypass surgery but rarely after coronary vasospasm. A case of stunned myocardium caused by diffuse coronary artery vasospasm and mimicking myocardial infarction is reported. The patient had an emergency coronary angiography, which showed no pathological coronary disease, but the left ventricular ejection fraction showed severe left ventricular dysfunction. Repeat coronary angiography 24 days later after medical treatment (diltiazem and nitrates) showed complete recovery of wall function, and a diffuse vasospasm was induced in both coronary arteries (left anterior and right coronary arteries). Two days later the patient underwent a positron emission tomography study with water labelled with oxygen-15 to evaluate the viable myocardium and oxygen-15 to evaluate oxidative metabolism. The results showed normal myocardial blood flow and perfusable tissue density, confirming that the myocardium was viable, and normal myocardial oxidative metabolism, reflecting the recovery of the left ventricular function. PMID- 7888267 TI - Haemochromatosis presenting as congestive cardiac failure. AB - A 24 year old man with congestive cardiac failure was found to have grossly increased transferrin saturations, raised serum ferritin, and an iron-laden myocardium on biopsy. Initial treatment with the iron chelator desferrioxamine was replaced by weekly venesection. He was placed on the cardiac transplant list because of severe left ventricular dysfunction but was later removed because his symptoms and function improved. He remains well with few symptoms and is maintained on regular venesection and testosterone injections. PMID- 7888268 TI - Electrophysiology in a district general hospital. AB - OBJECTIVE: To investigate the feasibility of performing electrophysiological studies at a district general hospital and to evaluate the importance of such studies in the management of patients with suspected arrhythmias. DESIGN: Retrospective study of patients having had electrophysiological studies during a three year period. SETTING: District general hospital. SUBJECTS: 93 patients (50 men, 43 women, mean age 45.9 years) with suspected arrhythmias. RESULTS: The patients were divided into two groups according to symptoms. Group 1 (34 patients) presented with syncope. Group 2 (59 patients) presented with palpitation. All had previously undergone non-invasive investigations. All had had multiple hospital admissions and outpatient attendances. In group 1 nine patients with no documented arrhythmias had inducible ventricular tachycardia and three of six with suspected bradyarrhythmias had ventricular tachycardia. Fourteen patients had suspected ventricular arrhythmias before electrophysiological studies, which were confirmed in all, four receiving automatic implantable cardioverter defibrillators. Electrophysiological studies were used to guide drug treatment in all patients. Group 2 consisted of 32 patients with reentrant supraventricular tachycardia and 15 with ventricular tachycardia; 12 had no documented arrhythmias. In those with supraventricular tachycardia, accessory pathways were identified in all. In 23 patients drug treatment (guided by electrophysiological studies) was successful. In nine, drug treatment guided by electrophysiological studies were ineffective and radiofrequency ablation was successful. In 15 patients with ventricular tachycardia and palpitations, 10 had their drugs changed after electrophysiological studies and their ventricular tachycardia was suppressed. In five patients electrophysiological studies showed that ventricular tachycardia was unsuppressed and they were referred for an operation or implantation of an automatic cardioverter defibrillator. In 12 patients with no documented arrhythmias electrophysiological studies identified significant arrhythmias in six. There were no complications. CONCLUSIONS: Diagnostic electrophysiological studies can safely and effectively be performed in a district general hospital. These studies are especially effective in investigating patients with syncope, and also provide a strategy for future arrhythmia management. PMID- 7888269 TI - A New Year toast ... to the cardioprotective effects of alcohol. PMID- 7888270 TI - Immediate and long-term clinical outcome of coronary angioplasty in patients aged 35 years or less. AB - OBJECTIVE: To study the immediate and long-term clinical success of percutaneous transluminal coronary angioplasty in patients aged 35 years or less. DESIGN: Patients undergoing percutaneous transluminal angioplasty were prospectively entered into a dedicated database. Clinical and angiographic data on all patients aged 35 years or less were reviewed. Follow up data were collected by interview during outpatient visits, by questionnaire, or from referring physicians. SETTING: A tertiary referral cardiac centre. PATIENTS: 57 patients aged 35 years or less (median 33, range 22-35) underwent coronary angioplasty because of unstable angina (32 patients), stable angina (23 patients), acute myocardial infarction (1 patient), and documented ischaemia in a cardiac transplant patient. RESULTS: The primary clinical success rate (reduction in diameter stenosis to < 50% without in-hospital events) was 88%. A major procedure related complication occurred in 5 patients (9%): one patient died, two patients sustained an acute myocardial infarction, two patients underwent emergency bypass surgery, and in three patients repeat angioplasty was performed before hospital discharge. In 2 patients (4%) coronary angioplasty did not significantly reduce the diameter stenosis but there were no associated complications. A total of 60 lesions were attempted (balloon angioplasty in 57, directional atherectomy in 2). The initial angiographic success rate was 92%. The median (SD) follow up was 4.7 (3.0) years. During follow up 7 patients (12%) died, 10 sustained a myocardial infarction (18%), and 28 patients (49%) underwent repeat revascularisation (coronary artery bypass grafting in 7 (12%) and repeat angioplasty in 21 (37%)). The estimated 5 year survival and event-free survival (Kaplan-Meier method) was 87 (9)% and 50 (13)%, respectively. Multivariate logistic regression analysis showed that hypertension and the extent of vessel disease were the only independent predictive factors for event free survival. CONCLUSIONS: In young patients coronary angioplasty had a high immediate success rate but many needed repeat revascularisation procedures during the follow up period and survival was not improved. Coronary angioplasty in young patients should be regarded as a palliative procedure. PMID- 7888271 TI - Women and myocardial infarction: agism rather than sexism? AB - OBJECTIVE: To determine whether women with myocardial infarction are treated differently from men of the same age and to assess the effect of changes in the coronary care unit admission policy. DESIGN: Clinical audit. SETTING: The coronary care unit and general medical wards of a teaching hospital. In 1990 the age limit for admission to coronary care was 65 years. This age limit was removed in 1991. PATIENTS: 539 female and 977 male patients admitted with myocardial infarction between 1990 and 1992. MAIN OUTCOMES: Admission to the coronary care unit, administration of thrombolysis, and in-hospital mortality. RESULTS: 409 men and 254 women were admitted with myocardial infarction in 1990 and 568 men and 285 women in 1992. Removal of the age limit for admission to the coronary care unit resulted in an increase in the numbers of both sexes admitted with myocardial infarction. In both years, however, proportionately more men with infarction were admitted to coronary care: 226 men (55%) and 96 women (38%) (P < 0.01) (95% CI 7 to 28) in 1990 and 459 men (81%) and 200 women (70%) (P < 0.01) (%CI 2 to 19) in 1992. Some 246 men (60%) and 133 women (52%) with infarction (P < 0.01) received thrombolytic treatment in 1990 compared with 319 men (56%) and 130 women (46%) (P < 0.01) in 1992. The mean age of women sustaining a myocardial infarction was significantly greater in both years studied. In 1992 a total of 78 men (7%) and 34 women (4%) (P < 0.05) admitted with chest pain underwent cardiac catheterisation before discharge from hospital. CONCLUSIONS: Differences in admission rates to the coronary care unit and the rate of thrombolysis between the sexes can be explained by the older age of women sustaining infarction. The application of age limits for admission to coronary care or administration of thrombolysis places elderly patients at a disadvantage. As women sustain myocardial infarctions at an older age they are placed at a greater disadvantage. PMID- 7888272 TI - Determinants of the length of stay in intensive care and in hospital after coronary artery surgery. AB - BACKGROUND: Patients who have coronary artery surgery normally occupy intensive care beds for less than 24 hours. Longer stays may result in under use of cardiac surgical capacity. One approach to optimise surgical throughput is prospectively to identify fast track patients--that is, those who occupy an intensive care bed for less than 24 hours. A prospective audit of patients was performed to identify fast track patients by simple clinical criteria. Total length of hospital stay was also assessed in an attempt to predict which patients were likely to have a short postoperative stay, defined as < or = 7 days. METHODS: Baseline demographic details, cardiovascular risk factors, angiographic and operative details were recorded for 431 consecutive patients who underwent coronary surgery at a regional centre over a nine month period. Outcome measures were the duration of the stay in the intensive care unit in hours and total duration of the postoperative stay in hospital in days. In addition, two groups of patients who were thought to be fast track were identified prospectively. Fast track 1 patients were identified by criteria selected by cardiovascular physicians. These were age less than 60 years, stable angina, good left ventricular function (ejection fraction > 50%), good renal function (serum creatinine < 120 mumol/l), and no obesity, diabetes, or other serious disease. Fast track 2 patients were identified by criteria defined by cardiovascular surgeons. These were male sex, age less than 65 years, good left ventricular function and no peripheral vascular disease, diabetes, or other serious disease. The efficacy of both sets of criteria in predicting outcome was tested. RESULTS: 344 (79.8%) patients were fast track. Significant factors for the prediction of fast track patients by univariate analysis (with positive predictive accuracy and sensitivity) were left ventricular ejection fraction > 50% (83%, 80%), left ventricular end diastolic pressure < 13 mm Hg (90%, 59%), creatinine less than 120 mumol/l (83%, 87%), and one or two vessel coronary disease (89%, 34%). Of the patients categorised as fast track 1 89% proved to be fast track (sensitivity 24%), however, the fast track 2 characteristics were not significant. Age, sex, obesity, diabetes, hypertension, a history of obstructive pulmonary disease and unstable angina were not predictive of the duration of intensive care stay. Multivariate analysis indicated that only left ventricular end diastolic pressure and the number of diseased coronary arteries predicted fast track patients. These criteria separated patients into three groups. Those who were good risk had one or two vessel disease and left ventricular end diastolic pressure < 13 mm Hg. They comprised 19% of the total and 93% of them were fast track. Those who were intermediate risk had either three vessel disease or left ventricular end diastolic pressure > 13 mm Hg but not both. They comprised 49% of the total and 85% of them were fast track. Those who were poor risk had both three vessel disease and left ventricular end diastolic pressure > 13 mm Hg. They comprised 32% of the total and 62% of them were fast track. The 106 (24%) patients who spent < or = 7 days in hospital after surgery were significantly younger (mean (SD) 55(8) v 58(8) years; P < 0.001) with a lower incidence of previous myocardial infarction (positive predictive accuracy 30%, sensitivity 53%), were less likely to have a history of obstructive pulmonary disease (25%, 98%), and more likely to have one or two vessel coronary disease (33%, 41%). They were more likely to have an internal mammary artery as a bypass conduit (27%, 89%) and more likely to need fewer than three distal anastomoses of the vein graft (29%, 63%). By multivariate analysis only age was significantly predictive of hospital stay. Total hospital stay could not be satisfactorily modelled on the basis of the criteria tested here. Sex, obesity, diabetes, hypertension, unstable angina, renal function, and left ventricular function were not associated with hospital stay. CONCLUSIONS-Most patients who had coronary artery surgery spent less than or equal to 24 hours in intensive care, but most spent > 7 days in hospital. The chance of a patient spending less than or equal to 24 hours in intensive care could be predicted by the number of coronary arteries diseased and the left ventricular end diastolic pressure. Poor risks patients (32%) had only a 62% chance of an intensive care unit stay of less than or equal to 24 hours. A policy of scheduling no more than one such patient for surgery per day would be simple to institute and would maximise the use of surgical capacity. PMID- 7888273 TI - Endotracheal tolazoline for severe persistent pulmonary hypertension of the newborn. AB - The condition of a neonate with severe persistent pulmonary hypertension who became severely hypoxic and acidotic despite intensive conventional treatment improved dramatically after endotracheal administration of tolazoline. This logical mode of administration of vasodilator therapy for this condition has not been reported before. It seemed to be life saving in this case and it warrants further clinical trial. PMID- 7888274 TI - Changes of serum copper and zinc levels in patients with nasopharyngeal carcinoma by radiotherapy. AB - Serum copper levels (SCL) and serum zinc levels (SZL) were evaluated in 128 patients with nasopharyngeal carcinoma (NPC) of varying stages before, during, and after radiotherapy, and then compared with normal age-matched subjects. Among these patients, there were 119 undifferentiated squamous cell carcinoma, 5 differentiated squamous cell carcinoma, and 4 moderately differentiated squamous cell carcinoma, respectively. Before radiotherapy, SCLs were significantly higher in NPC patients than in normal subjects, but the difference of SZLs was not significant. The ratio of Cu/Zn also showed a significant difference between normal subjects and NPC patients preradiotherapy. Moreover, except stage II, patients with more advanced stages of the disease had more elevated Cu/Zn ratios. During and after the period of radiotherapy, the SCL decreased as compared with the level of preradiotherapy. The Cu/Zn ratio also decreased after radiotherapy but not significant. However, Cu/Zn ratio of expired patients at least 2 yr after radiotherapy did not show the significant decrease in contrast to the alive ones. PMID- 7888275 TI - The role of ATP as a mediator in the action of iron complexes on cellular calcium homeostasis. AB - The effects of the interaction between low molecular weight iron complexes (citrate, lactate, and ATP complexes) with ATP and proteins, on the modification of Ehrlich carcinoma cell calcium homeostasis have been studied. In that modification the ferric-ATP complex shows much higher activity than the others. Sodium ATP, by iron translocation from citrate and lactate, increases their activity. This phenomenon implicates ATP as a mediator on the cellular activity of the complexes. Proteins, particularly ferritin, appear to moderately reduce their activity, whereas glutathione and ascorbic acid, acting as lipid peroxidation-inhibitors, show only a slight reduction of the iron complex's effects on cellular calcium uptake. PMID- 7888276 TI - Selenium enhances glutathione peroxidase activity and prostacyclin release in cultured human endothelial cells. Concurrent effects on mRNA levels. AB - Selenium (Se) is an essential component of glutathione peroxidase (GSH-Px), an enzyme that protects cells by reducing intracellular peroxides. Impaired Se status and GSH-Px activity seem associated with increased risk of atherosclerotic vascular diseases. This study reports the effects of Se supplementation on GSH-Px activity, on prostacyclin (PGI2) production, on 12-hydroxy-eicosatetraenoic acid (12-HETE) levels, and on GSH-Px mRNA expression in cultured human umbilical vein endothelial cells (HUVEC). Se-enriched HUVEC showed significant increase of both GSH-Px activity and thrombin-stimulated production of PGI2 in the presence of stable concentrations of 12-HETE. On the other hand, an inverse correlation between Se concentrations in culture media and GSH-Px mRNA levels in Northern blot analysis was shown; this suggests that a major degree of regulation for GSH Px expression by Se is most likely exerted at the posttranscriptional level. These observations may help to explain the increased incidence of atherosclerosis described in Se-deficient individuals. PMID- 7888277 TI - Biliary excretion of copper in Fischer rats treated with copper salt and in Long Evans cinnamon (LEC) rats with an inherently abnormal copper metabolism. AB - Increased biliary Cu excretion was found in Fischer rats injected with Cu. The biliary Cu was located at the void (large-molecule region) and total (small molecule region) volume of a Sephadex G-75 column. The most Cu was found in the total volume. The two Cu peaks comigrated with absorbance at 280 nm. Although the bile from Cu-untreated Fischer rats did not show Cu absorbance in the total volume, absorbance at 280 nm was also found in this region. Even though Long Evans Cinnamon (LEC) rats deposited a gross amount of Cu (194.0 +/- 27.8 micrograms/g liver) in the liver, they conversely showed reduced Cu excretion into the bile. LEC bile did not show Cu absorbance but rather absorbance at 280 nm in the total volume. Therefore, it seems unlikely that the small molecules found in the Sephadex G-75 regulate biliary Cu excretion in Cu-loaded rats, although the molecules bind to Cu. When the bile from Cu-untreated Fischer and LEC rats was incubated with CuCl2 solution, the most Cu was recovered in the total volume of this column. Our results suggest that reduced biliary Cu excretion in LEC rats is not related to the small molecules, and that Cu cannot be excreted in the form of macromolecules in rats to decrease Cu from the Cu loaded liver. PMID- 7888278 TI - Does dietary arsenic and mercury affect cutaneous bleeding time and blood lipids in humans? AB - Fish species may contain considerable amounts of trace elements, such as selenium (Se), arsenic (As), and mercury (Hg). The present study investigated the relationships between dietary intake of these elements and cutaneous bleeding time and blood lipids in 32 healthy volunteers. For 6 wk, one group (n = 11) consumed approx 250 g Se-rich fish daily, providing them with an average Se intake of 115 +/- 31 micrograms Se/d, Hg intake of 18 +/- 8 micrograms/d, and As intake of 806 +/- 405 micrograms/d, all values analyzed in 4-d duplicate food collections. To study the effect of Se alone, one group (n = 11) included Se-rich bread in their normal diet, giving them a Se intake (135 +/- 25 micrograms/d) that was comparable to the fish group. A control group (n = 10) ate their normal diet, providing 77 +/- 25 micrograms Se/d, 3.1 +/- 2.5 micrograms Hg/d, and 101 +/- 33 micrograms As/d. The dietary As load strongly correlated both with bleeding times and changes in bleeding times (r = 0.48, p < 0.01 and r = 0.54, p < 0.002, respectively). Dietary Hg showed a positive correlation with LDL cholesterol (r = 0.55, p < 0.01), whereas dietary Hg in the fish group showed a strong negative relationship with HDL-cholesterol (r = -0.76, p < 0.01). Selenium seemed to have only a modest effect on bleeding time. Our results suggest that mercury and arsenic from fish may be factors contributing to or modifying some of the known effects of fish ingestion. PMID- 7888279 TI - Combined action of lead and lithium on essential and nonessential elements in rat blood. AB - The effects of lead and lithium ingestion, separately and in combination, on the levels of K, Fe, Cu, Zn, Br, Rb, and As in rat blood were studied by the Energy Dispersive X-ray Fluorescence technique. Two different doses of lead acetate, i.e., 50 and 100 mg/Kg body wt (low and high doses), were administered orally to rats, daily, for 1 and 4 months (short and long terms), whereas lithium in the form of lithium carbonate was given to rats in food (1.1 g/kg diet) for 1 and 4 mo separately, and also to rats receiving lower and higher doses of lead. K levels were found to be depressed significantly with lead treatment, whereas Fe contents were enhanced marginally after 1 mo of treatment when only the higher dose of lead was given. As, Br, and Rb contents were found to be elevated following lead treatment for short and long terms at both the dose levels. However, Cu contents were lowered, whereas Zn contents were raised only after long term treatment with lead. The Fe, Cu, As, and Br contents remained unaltered, whereas K, Rb, and Zn contents were reduced significantly when lithium was administered for short term. Moreover, Cu and Fe levels were also found to be reduced and Br contents were enhanced only after long term treatment. During the combined treatment with lead and lithium for short and long terms, the levels of K, As, and Rb were observed to decrease, whereas Fe contents were enhanced when estimated for both doses of lead. On the contrary, Cu levels were lowered only with the higher dose of lead acetate when given in combination with lithium for 1 and 4 mo. Br contents were only effectively decreased after 4 mo of treatment. PMID- 7888280 TI - The IgM and IgG antibody responses in iron-deficient and iron-loaded mice. AB - The humoral immune response was evaluated in male CD-1 mice fed the iron deficient (7 ppm Fe), iron sufficient (120 ppm Fe), and high-iron diets (3000 or 5000 ppm Fe) for 54 d. The IgM and IgG antibody responses against sheep erythrocytes (SRBC) determined by hemolytic plaque assay were suppressed by 65.4 and 51.2%, respectively, in the iron deficient mice. Subclinical iron deficiency was manifested by a marked reduction in hepatic iron concentration without any changes in hematocrit or body weight gain. In contrast, consumption of high-iron diets caused a marked accumulation of iron in the liver and a twofold reduction in the IgM antibody response without alteration in the IgG response. The suppression of the IgG antibody response in the iron deficient mice, however, did not result in a compensatory increase in delayed type hypersensitivity response. PMID- 7888281 TI - Serum selenium levels in Slovak population. AB - Blood serum selenium levels were measured in 576 healthy middle aged adults (40 60 yr, 255 men and 321 women) residing in both urban and rural areas in four districts of Slovakia. Serum selenium was determined by electrothermal AAS. The mean (+/- SD) serum selenium concentration was 0.852 +/- 0.335 mumol/L, ranging from 0.219-2.30 mumol/L. A large proportion of the individuals (19.62%) exhibited serum selenium levels under 0.57 mumol/L (45 mumol/L). There was no significant correlation between serum selenium concentration and age, sex, and smoking status. There were significant differences between districts. The lowest mean (+/ SD) serum selenium was 0.664 +/- 0.269 mumol/L, the highest mean serum selenium (+/- SD) was 0.975 +/- 0.361 mumol/L. This differences could probably be attributed to the selenium content in the soil of the different areas, which would contribute to the average daily selenium intake. In comparison with serum selenium levels in other European countries, the concentrations of selenium in the Slovak population are relatively low. PMID- 7888282 TI - Selenium-containing peroxidases of germinating barley. AB - Germinating barley grown on an artificial medium was exposed to 75Se-selenite for 8 d. Then the leaves were homogenized and proteins were separated by means of Sephadex G-150 filtration, followed by DEAE-Sepharose chromatography. Each fraction collected was assayed for total protein, radioactivity, and peroxidase activity. In barley leaves, three protein peaks (peaks no. I, II, and III) with peroxidase activity could be separated by Sephadex G 150 filtration. Each fraction was then further separated on DEAE-Sepharose chromatography. Thus, peaks I and II were resolved by DEAE-Sepharose into one major and two minor peaks of radioactivity. However, only the major peak showed peroxidase activity. Peak III was resolved from the gel filtration on the DEAE-sepharose into one major and four minor peaks of radioactivity. The major and three of the minor radioactivity peaks contained peroxidase activity. The protein fractions were separated by polyacrylamide gel electrophoresis. The molecular weights of separated proteins were estimated by means of molecular markers, and 75Se radioactivity was evaluated by autoradiography. Thus, gel filtration peak I contained four bands with mol wts of 128, 116, 100, and 89 kDa. Of these, the 89 kDa protein contained selenium. Peak II contained three protein bands with mol wts 79.4, 59.6, and 59.9. The 59.6 band was a selenoprotein. Peak III contained four protein bands (and some very weak bands). The four major bands had mol wts of 38.6, 31.6, 30.2, and 29.2 kDa. The last mentioned band was a selenoprotein. PMID- 7888283 TI - Zinc exchange by blood cells in nearly physiologic standard conditions. AB - Determination of zinc concentrations in white blood cells has been used to establish zinc deficiency. During pathological conditions changes in zinc concentrations in these blood cells were observed. However, these investigations were hampered by the low amount of zinc in this form per mL blood. Earlier we demonstrated that, in the case of zinc deficiency, the uptake of zinc was increased, using the in vitro exchange of zinc by the various blood cells with extracellular zinc labeled with 65Zn in fairly physiologic conditions. In case of inflammation, no increase in zinc uptake by erythrocytes was seen, indicating that this method probably can be used to differentiate real from apparent zinc deficiency. Only during the first days of the inflammatory process, probably representing the redistribution phase during which zinc moves from the serum to the liver, a small increase in in vitro zinc uptake was seen in mononuclear cells (MNC) and polymorphonuclear cells (PMNC). Earlier papers raised some questions; e.g., is the uptake part of an exchange process and can the efflux of zinc by the cells be measured by the same method; what is the influence of time on the process of zinc uptake; what is the magnitude of the uptake of zinc by the cells compared to the zinc concentration in the cells; and, what is the influence of temperature on the uptake of zinc? In the present study, the influence of incubation time and temperature on the uptake of zinc by human and rat blood cells and on the release of zinc by rat blood cells was studied. At least three phases of uptake of zinc in the various cells were found by varying the incubation time--a fast phase during the first half hour, probably caused by an aspecific binding of zinc on or in the cell membrane; a second fast uptake between 60-330 min, probably caused by an influx of zinc in the cell as part of the exchange process of zinc; and a slow third phase after 5.5 h, in which probably the in- and efflux of the rapidly exchangeable intracellular pool is more or less equilibrated. For mononuclear cells, polymorphonuclear cells, and erythrocytes of rats, the rapidly exchangeable intracellular pool is 40%, 53%, and 10%, respectively, of the total zinc content of the cells. This study is also performed in human cells; in human cells the exchangeable pool of mononuclear cells and erythrocytes is 17 and 3.5% of the total zinc content of the cells, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7888284 TI - Comparative aspects of cardiac ultrastructure, morphometry, and electrocardiography of hearts from rats fed restricted dietary copper and selenium. AB - Comparative cardiac ultrastructure, morphometry, and electrocardiography after dietary copper and selenium restriction were examined. Male weanling Long-Evans rats were fed diets that were either adequate in both copper and selenium (Cu+/Se+) or restricted in either Cu (Cu-) or Se (Se-) for 8 wk. At wk 8, electrocardiograms (ECG) and dP/dts were obtained and heart tissue was utilized for electron microscopy. Upon examination, Cu- rats were anemic, exhibited a greater heart: body weight ratio, and developed concentric hypertrophy characterized by an enhanced thickening of the left and right ventricular free walls, and interventricular septum. ECG recordings from lead aVF in the Cu- group showed a greater R wave amplitude in comparison to the Cu+/Se+ group. Se- rats recorded a greater left ventricular +dP/dtmax than both the Cu+/Se+ and Cu- groups. Cardiac myofibril volume densities were decreased in both Cu- and Se- rats in comparison to the Cu+/Se+ rats. In addition Cu- rats showed a greater mitochondria:myofibril ratio. Sarcomere contractile protein disarray was present in both the Cu- and Se- groups. Se- myocytes also showed evidence of edema and mitochondrial fragmentation. The subcellular alterations suggest that similarities exist in the cardiac remodeling processes associated with copper and selenium restrictions. PMID- 7888286 TI - The use of nitrates, calcium channel blockers and ACE inhibitors in primary care in the Northern Region: a pharmacoepidemiological study. AB - 1. Prescribing rates for cardiovascular drugs have substantial local variation. The objectives of this study were to determine the prescribing prevalence of nitrates, calcium channel blockers and angiotensin-converting enzyme inhibitors in general practice, to examine the indications recorded for these prescriptions, and to identify which therapeutic areas contribute to the variation in prescribing. 2. Anonymised patient-specific prescription data were taken from computerised records in 41 VAMP research practices in the Northern Region (total population 330,749). All patients who received any prescription for calcium channel blockers, nitrates or angiotensin-converting enzyme (ACE) inhibitors during a 12 month period were included. Prescribing rates were determined in terms of patients per 1,000 population within age, sex and diagnostic groups. 3. Overall, 4.3% of the study population were prescribed one or more of the drugs. There was virtually no prescribing for patients under the age of 35 years, but thereafter the prevalences rose steeply to peak at ages 65-74 years for calcium channel blockers (91 per 1,000 population) and ACE inhibitors (34 per 1,000), and at ages 75-84 years for nitrates (100 per 1,000). Prescribing prevalence amongst the over 85's was less than half the peak rate for each drug group. Rates for men and women were comparable, except for nitrates where men had higher rates. 4. Recorded indication rates for patients with ischaemic heart disease and treated with any of these drugs reached 112 per 1,000 population in the 75-84 age group, and were higher in men than women, at all ages. Hypertension indication rates were substantially higher in women over 65; across the genders the peak rate was 88 per 1,000 for those aged 65-74 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888285 TI - Influence of 12-week nicotine treatment and dietary copper on blood pressure and indices of the antioxidant system in male spontaneous hypertensive rats. AB - Nicotine treatment and copper (Cu) deficiency have been associated with an increased production of reactive oxygen species that may contribute to the development and/or progression of cardiovascular diseases (CVD). The present study investigated the influence of dietary Cu intake on the response to chronic nicotine treatment in spontaneous hypertensive rats (SHR) with respect to tissue trace mineral levels, several components of the oxidant defense system, and lipid peroxidation rates. SHR weighing 100-110 g were fed a Cu deficient diet (-Cu) (0.5 microgram Cu/g) for 14 d prior to nicotine treatment. SHR were inserted with tablets that released nicotine at a rate of 75 micrograms/h or placebo (control). Following tablet insertion, rats were fed a control diet (+Cu) (12.0 micrograms Cu/g) or the -Cu diet. Nicotine treatment lasted for 12 wk. Blood pressure (BP) was higher in nicotine-treated SHR than in control SHR at wk 3; BP was unaffected by diet. BP was higher in +Cu nicotine-treated SHR at wk 6 compared to -Cu nicotine and control rats. BP was not affected by nicotine or diet at wk 2. Liver, heart, and brain Cu levels and liver, heart, and red cell CuZn superoxide dismutase and plasma ceruloplasmin oxidase activities were lower in the -Cu SHR than in the +Cu SHR. Liver Fe levels were higher and plasma Fe levels were lower in the -Cu rats than in the +Cu rats. Liver selenium-dependent-glutathione peroxidase (Se-GSH-Px) activity was lower in the -Cu rats than in the +Cu rats; heart and thoracic aorta Se-GSH-Px activity was unaffected by -Cu diet. Thoracic aorta, liver, and heart GSH-reductase activities were unaffected by treatments. Plasma thiobarbituric acid reactive substances (TBARS) were higher in the -Cu than in the +Cu SHR. Liver and heart TBARS production was similar among the groups. These data show that nicotine can exacerbate the development of high BP in susceptible individuals; Cu deficiency did not exacerbate the effects of nicotine. PMID- 7888287 TI - Exercise metabolism in healthy volunteers taking atenolol, high and low doses of metoprolol CR/Z0K, and placebo. AB - 1. Exercise and beta-adrenoceptor blockade have important roles in the prevention and treatment of cardiovascular disease, but fatigue and a reduced capacity to exercise are commonly reported side effects of beta-adrenoceptor blockers. The reduced capacity to exercise may be partly caused by a reduction in fat metabolism. 2. We investigated the effects of atenolol 50 mg, metoprolol CR/Z0K 50 mg, metoprolol CR/Z0K 100 mg and placebo, on heart rate, energy expenditure, fat oxidation, plasma free fatty acids, glycerol, glucose, lactate, ammonia and perceived exertion during 2 h of treadmill walking at 40% of maximal oxygen uptake in 20 healthy volunteers. 3. Compared with placebo (38.0%), total fat oxidation was significantly lower on atenolol 50 mg (30.1%) and metoprolol CR/Z0K 100 mg (31.0%), but not on metoprolol CR/Z0K 50 mg (33.7%). Reductions in fat oxidation correlated well (r2 = 0.970) with reductions in exercising heart rate, and probably reflected the degree of beta 1-adrenoceptor blockade. Maximum plasma ammonia concentration was reached after 45 min of exercise on atenolol, 60 min on metoprolol CR/Z0K 100, and 75 min on metoprolol CR/Z0K 50, and was higher than placebo on all active drug treatments. 4. The greater reduction in fat oxidation with atenolol may be a reflection of a peak in plasma concentration, which is avoided with a controlled release preparation. PMID- 7888289 TI - Pravastatin inhibits cellular cholesterol synthesis and increases low density lipoprotein receptor activity in macrophages: in vitro and in vivo studies. AB - 1. Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) inhibitor, is a highly selective inhibitor of hepatic cholesterol synthesis. We studied the in vivo and in vitro effects of pravastatin on macrophage cholesterol metabolism. 2. The effects of incubating pravastatin with human monocyte derived macrophages (HMDM), mouse peritoneal macrophages (MPM) and a J-774 A.1 macrophage-like cell line, on macrophage cholesterol synthesis, cellular degradation of native low density lipoprotein (LDL) and modified LDL, cholesterol efflux from these cells and the cholesterol esterification rate were determined. 3. Pravastatin was administered either as one 40 mg dose or 40 mg daily for 8 weeks to normocholesterolaemic and hypercholesterolaemic individuals. The effects on cholesterol synthesis and degradation in monocytes derived from these subjects were studied. 4. In vitro, pravastatin resulted in a dose-dependent inhibition of macrophage cholesterol synthesis. Cellular degradation of native LDL increased by 119% in the presence of 0.1 mg ml-1 pravastatin. Degradation of both acetyl LDL and oxidized LDL was unaffected. Small concentrations of pravastatin (up to 0.19 micrograms ml-1) increased the cellular cholesterol esterification rate after incubation with LDL, but higher concentrations resulted in an inhibition of the esterification. 5. Single dose pravastatin administration caused a reduction in cholesterol synthesis by the subjects own HMDM by 62% and 47% in normocholesterolaemic and hypercholesterolaemic individuals, respectively. Chronic administration resulted in a 55% inhibition of cholesterol synthesis and a 57% increase in LDL degradation. 6. The results indicate that the selective uptake of pravastatin shown for hepatocytes can be extended to macrophages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888288 TI - Interaction between endothelin and vasodilators in the human internal mammary artery. AB - 1. The internal mammary artery (IMA) is the primary choice as an arterial graft for coronary artery bypass surgery. Endothelin (ET) has been recently measured with an increased release after cardiopulmonary bypass for coronary artery bypass grafting. Threshold concentrations of ET-1 have been found to amplify specifically contractions induced by noradrenaline and serotonin. This study was designed to investigate the effect of glyceryl trinitrate (GTN) and calcium antagonists on ET-1 contraction in the human IMA. 2. Human IMA segments taken from 21 patients undergoing IMA-coronary artery bypass grafting were mounted in an organ bath under the physiological pressure determined from their own length tension curves. Four ring segments were allocated into four groups. One served as a control and the others were treated with GTN (10, 100 nM, or 30 microM) for 5 min or nifedipine (20 or 200 nM, or 30 microM) for 25 min before concentration contraction curves to ET-1 were established. In separate experiments, the concentration-relaxation curves to GTN or nifedipine were established in the IMA rings precontracted with ET-1 (10 nM). 3. Pretreatment of IMA with GTN for 5 min did not alter the ET-1-induced contraction. Pretreatment with 20 or 200 nM of nifedipine slightly but not significantly, altered the maximum contraction induced by ET-1. Higher concentrations (30 microM) significantly reduced the maximum contraction force (P = 0.008). On the other hand, GTN caused 76.44 +/- 6.35% relaxation in ET-1-precontracted IMA. In contrast, the nifedipine-induced relaxation was difficult to establish due to unsustained contraction to ET 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888290 TI - An assessment of the systemic activity of single doses of inhaled fluticasone propionate in healthy volunteers. AB - 1. The systemic effects of inhaled fluticasone propionate (FP), administered via Diskhaler, on the hypothalamo-pituitary-adrenal (HPA) axis were assessed primarily by measuring plasma cortisol at frequent intervals for 20 h after drug administration. 2. FP showed a dose-related suppression of plasma cortisol measured as area under the plasma cortisol vs time curve (AUC 0-20). The cortisol suppression (expressed as % fall from placebo) was 8, 19, and 28% for single doses of 250 micrograms FP, 500 micrograms FP and 1000 micrograms FP, respectively. A single dose of budesonide, 800 micrograms (via Turbuhaler), resulted in a 16% cortisol suppression. The cortisol suppression for all three single doses of FP, and for the single dose of budesonide, was statistically significantly different from placebo. 3. Repeated dosing of FP (1000 micrograms twice daily for 3.5 days) resulted in a more marked plasma cortisol suppression; a fall of 65% from placebo (AUC FP 1000 mg twice daily vs AUC placebo, P < 0.001). 4. In a well-controlled study in healthy volunteers, inhaled FP, in therapeutic doses, was shown to exhibit systemic effects which appear to be more pronounced after repeated dosing. PMID- 7888291 TI - A comparison of the systemic bioactivity of inhaled budesonide and fluticasone propionate in normal subjects. AB - 1. The aim of this study was to compare the systemic bioactivity of low and high doses of inhaled budesonide and fluticasone propionate given by respective dry powder inhaler devices. 2. A randomised, single blind cross-over design was used in nine healthy subjects who were given 800 micrograms day-1 of budesonide Turbohaler (B800) for 1 week, followed by 1 week of 1600 micrograms day-1 (B1600), or fluticasone Diskhaler 750 micrograms day-1 (F750) for 1 week followed by 1 week of 1500 micrograms day-1 (F1500). There was a 1 week washout between treatments with fluticasone or budesonide. A twice daily dosing regime was used and mouth-rinsing was employed to reduce gut bioavailability as well as to obviate local adverse effects. 3. Parameters of hypothalmic-pituitary adrenal (HPA) axis activity and bone metabolism were measured at baseline (B0/F0), at the end of each week of treatment and after the 1 week washout (F0 or B0). 4. Both fluticasone and budesonide significantly (P < 0.05) attenuated the post tetracosactrin serum cortisol at low and high doses whilst early morning cortisol was unchanged. No dose-response effect was observed with either drug, and there was no significant difference between treatment with fluticasone or budesonide. 5. Neither budesonide nor fluticasone produced significant suppression of plasma osteocalcin, although the higher doses of both drugs significantly reduced fasting urinary calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888293 TI - Different sensitivity of pain-related chemosensory potentials evoked by stimulation with CO2, tooth pulp event-related potentials, and acoustic event related potentials to the tranquilizer diazepam. AB - 1. The aim of this study was to investigate the sensitivity of pain-related potentials used in experimental pain models to the non-specific effects of the tranquilizer diazepam. Pain-related potentials were recorded after painful stimulation of the nasal mucosa with CO2 and after painful stimulation of the tooth pulp. Acoustically evoked potentials were measured in order to compare their sensitivity to the tranquilizer diazepam with the sensitivity of the pain related potentials. 2. Twenty volunteers participated in this randomised, double blind, three-fold crossover study. Measurements were obtained before and 20 min after the administration of the drug. Event-related potentials were recorded after painful stimulation of the nasal mucosa with CO2 (two stimulus intensities: 60% v/v and 70% v/v CO2), after painful stimulation of the tooth pulp (two stimulus intensities: 2.2 x and 3.3 x detection threshold), and after non-painful acoustical stimulation of the right ear. The subjects rated the perceived intensity of the painful stimuli by means of a visual analogue scale. In addition the spontaneous EEG was analysed in the frequency domain and the vigilance of the subjects was assessed in a tracking task. 3. Diazepam reduced significantly the amplitudes of the event-related potentials after painful stimulation of the tooth pulp and after acoustical stimulation. In contrast only a small, statistically non-significant reduction could be found after painful stimulation with CO2. The pain ratings of the painful stimuli were not affected by diazepam. Diazepam reduced the performance of the tracking task. A decrease of arousal could be found in the alpha 2-range, whereas in the beta 2 and the theta-range the power density increased under diazepam. 4. We demonstrated that event-related potentials after painful stimulation of the nasal mucosa with CO2 are less affected by the nonspecific effects of the tranquilizer diazepam than event related potentials after painful stimulation of the tooth pulp. The effects of diazepam on the tracking task, the spontaneous EEG and the event-related potentials clearly confirm its sedative properties. Diazepam had no analgesic effect measurable by pain intensity estimates. PMID- 7888292 TI - Analgesics and ENT surgery. A clinical comparison of the intraoperative, recovery and postoperative effects of buprenorphine, diclofenac, fentanyl, morphine, nalbuphine, pethidine and placebo given intravenously with induction of anaesthesia. AB - 1. Vomiting and restlessness following ENT and eye surgery are undesirable, and may be related to the emetic and analgesic effects of any analgesic given to augment anaesthesia during surgery. 2. To rationalise the choice of analgesic for routine ENT surgery we examined the intraoperative, recovery and postoperative effects following the administration of either buprenorphine (3.0 to 4.5 micrograms kg-1), diclofenac (1 mg kg-1), fentanyl (1.5 to 2.0 micrograms kg-1), morphine (0.1 to 0.15 mg kg-1), nalbuphine (0.1 to 0.15 mg kg-1), pethidine (1.0 to 1.5 mg kg-1) or saline (as control) given with the induction of anaesthesia in 374 patients. A standardised anaesthetic technique with controlled ventilation using 0.6-0.8% isoflurane in nitrous oxide and oxygen was employed. The study population constituted 7 similar groups of patients. 3. Intraoperatively, their effects on heart rate and blood pressure, airway pressure and intraocular pressure, were similar. This implies, most surprisingly, that neither their analgesic nor their histamine releasing effects were clinically evident during surgery. By prolonging the time to extubation at the end of anaesthesia, only buprenorphine, fentanyl, morphine and pethidine provided evidence of intraoperative respiratory depression. 4. Postoperatively, buprenorphine was associated with severe respiratory depression, prolonged somnolence, profound analgesia and the highest emesis rate. Diclofenac exhibited no sedative, analgesic, analgesic sparing, emetic or antipyretic effects. Fentanyl provided no sedative or analgesic effects, but was mildly emetic. Morphine provided poor sedation and analgesia, delayed the requirement for re-medication and was highly emetic. Nalbuphine and pethidine produced sedation with analgesia during recovery, a prolonged time to re-medication and a mild emetic effect. None provided evidence, from analysis of postoperative re-medication times and analgesic consumption, of any pre-emptive analgesic effect. 5. We conclude that nalbuphine (mean dose 0.13 mg kg-1) and pethidine (mean dose 1.35 mg kg-1), given individually as a single i.v. bolus during induction of anaesthesia, are the most efficacious analgesics for routine in-patient ENT surgery. PMID- 7888294 TI - Characterisation of the cytochrome P450 enzymes involved in the in vitro metabolism of granisetron. AB - 1. The metabolism of granisetron was investigated in human liver microsomes to identify the specific forms of cytochrome P450 responsible. 2. 7-hydroxy and 9' desmethyl granisetron were identified as the major products of metabolism following incubation of granisetron with human liver microsomes. At low, clinically relevant, concentrations of granisetron the 7-hydroxy metabolite predominated. Rates of granisetron 7-hydroxylation varied over 100-fold in the human livers investigated. 3. Enzyme kinetics demonstrated the involvement of at least two enzymes contributing to the 7-hydroxylation of granisetron, one of which was a high affinity component with a Km of 4 microM. A single, low affinity, enzyme was responsible for the 9'-desmethylation of granisetron. 4. Granisetron caused no inhibition of any of the cytochrome P450 activities investigated (CYP1A2, CYP2A6, CYP2B6, CYP2C9/8, CYP2C19, CYP2D6, CYP2E1 and CYP3A), at concentrations up to 250 microM. 5. Studies using chemical inhibitors selective for individual P450 enzymes indicated the involvement of cytochrome P450 3A (CYP3A), both pathways of granisetron metabolism being very sensitive to ketoconazole inhibition. Correlation data were consistent with the role of CYP3A3/4 in granisetron 9'-desmethylation but indicated that a different enzyme was involved in the 7-hydroxylation. PMID- 7888295 TI - Inhibition of caffeine metabolism by ciprofloxacin in children with cystic fibrosis as measured by the caffeine breath test. AB - The caffeine breath test was carried out in six children with cystic fibrosis, before and during a course of ciprofloxacin. There was a significant decrease in the 2 h cumulative labelled CO2 exhaled during ciprofloxacin treatment, mean difference (s.d.) -5.2(3.3)%, P < 0.02. The results suggest an inhibition of 3-N demethylation of caffeine (CYP1A2 enzyme activity) by ciprofloxacin. Ciprofloxacin may cause significant drug interactions in children with cystic fibrosis. The caffeine breath test can be used to study drug interactions involving CYP1A2 in children. PMID- 7888296 TI - Ranitidine bismuth citrate and ranitidine do not affect gastric emptying of a radio-labelled liquid meal. AB - Ranitidine bismuth citrate, a new chemical entity which is a salt complex of ranitidine and bismuth citrate, is being developed for the treatment of relapse of benign gastric and duodenal ulcer and eradication of Helicobacter pylori. The aim of the present study was to establish whether ranitidine bismuth citrate (800 mg) or ranitidine hydrochloride (300 mg) have any effect on gastric emptying of a liquid meal using gamma scintigraphy. On three separate occasions, each of twelve subjects received a single oral tablet of 800 mg ranitidine bismuth citrate, 300 mg ranitidine hydrochloride or placebo in random order. Thirty minutes after dosing each subject was given 375 ml of 99mTc-DTPA (diethylene triaminepentaacetic acid) labelled Clinifeed-ISO. The primary endpoint was the time to 50% gastric emptying (t50%). The proportion of the meal remaining was summarised by weighted mean proportion of the meal remaining in the stomach over 0-60 min and 0-180 min, separately. No differences were observed for t50%, weighted mean 0-60 min, and weighted mean 0-180 min between any two treatments. In man, we have detected no significant effect of single oral doses of ranitidine bismuth citrate 800 mg or ranitidine hydrochloride 300 mg on the rate of gastric emptying of a liquid meal when compared with placebo. PMID- 7888297 TI - N-acetylation genotype and risk of severe reactions to sulphonamides in AIDS patients. PMID- 7888298 TI - Non-genomic signal transduction pathway of vitamin D in muscle. AB - The secosteroid hormone 1,25(OH)2-vitamin D3 rapidly activates voltage-dependent Ca2+ channels of the L-type in skeletal and cardiac muscle cells by a non-genomic mechanism which involves guanine nucleotide binding (G) protein-medicated stimulation of the adenylate cyclase/cAMP/protein kinase A messenger system. Modifications in calmodulin intracellular distribution induced by PKA-dependent membrane protein phosphorylation may participate in the fast regulation of muscle Ca2+ influx by 1,25(OH)2D3. The protein kinase C pathway also plays a role modulating 1,25(OH)2D3 signal transduction in muscle by cross-talk with the PKA system. The hormone sequentially activates phospholipases C and D providing diacylglycerol for PKC activation and inositol triphosphate for intracellular Ca2+ mobilization. In addition, 1,25(OH)2D3 rapidly stimulates phospholipase A2 generating arachidonic acid for the eicosanoid pathway. Specificity of hormone effects suggests that binding to a muscle membrane-bound receptor mediates these events. PMID- 7888299 TI - Regulation of signalling pathways to the nucleus by dopaminergic receptors. AB - Dopamine regulates postsynaptic gene expression in the central nervous system. The pattern of gene expression is different from chronic vs acute stimulation of dopaminergic receptors. Signalling to the nucleus through dopamine receptors involves different second messenger systems, and each receptor subtype regulates multiple effectors. Long term adaptive changes in neuronal function following administration of dopaminergic drugs such as antipsychotic agent or drugs of abuse is one such example of molecular plasticity triggered by dopaminergic receptors. Role of dopaminergic receptors in the control of transcriptional events and immediate early gene regulation are reviewed. PMID- 7888300 TI - Lovastatin inhibits receptor-stimulated Ca(2+)-influx in retinoic acid differentiated U937 and HL-60 cells. AB - Lovastatin was used to study the role of isoprenylated proteins on stimulus induced increase of cytosolic Ca2+ in retinoic acid-differentiated U937 and HL-60 cells. Preincubation of the cells with lovastatin for 11-24 h reduced the Ca(2+) influx induced by PAF of FMLP. The maximal decrease was 60% in U937 cells and 40% in HL-60 cells. The ID50s of lovastatin in U937 and HL-60 cells were 5 microM and 15 microM, respectively. Lovastatin did not inhibit Ca(2+)-discharge from intracellular stores. Addition of mevalonate to lovastatin-treated cells completely reversed the inhibition of PAF- and FMLP-stimulated Ca(2+) mobilization. Immunoreactivity of ras-like proteins was decreased in membranes and increased in the cytosol of U937 cells by 1 day treatment with lovastatin. We conclude that isoprenylated proteins are involved in the regulation of receptor stimulated Ca(2+)-entry of differentiated HL-60 and U937 cells. PMID- 7888301 TI - Analogues of the thrombin receptor tethered-ligand enhance mesangial cell proliferation. AB - Thrombin stimulates cytosolic calcium mobilization and tritiated thymidine incorporation in rat glomerular mesangial cells. This effect may be mediated by a thrombin receptor similar to the receptor found in human platelets. In order to test this possibility, a series of analogues of the thrombin receptor peptide, SFLL-RNPNDKYEPF, was evaluated for their effects on mesangial cells. Analogues of the thrombin receptor peptide containing five, six, seven and 14 amino acids were as efficacious as thrombin with respect to calcium mobilization and thymidine incorporation, although they were significantly less potent. The dissimilarity in potency between thrombin and the thrombin receptor peptides is consistent with the kinetics of the proposed mechanism of action of the enzyme, since the cleavage by thrombin of its receptor results in a tethered ligand which is at a relatively high concentration compared to the free peptides in solution. Those thrombin receptor peptide analogues which showed decreased activity in platelets were tested in mesangial cells. Removal of serine at position one, N-acetylation, or replacement of the phenylalanine at position two with alanine resulted in analogues which were inactive in stimulating mesangial cell proliferation or calcium mobilization. In addition, those analogues which had no stimulatory effects in mesangial cells were not antagonists of SFLLRN-mediated calcium mobilization and thymidine incorporation in mesangial cells. PMID- 7888302 TI - Calmodulin function and calmodulin-binding proteins during autoactivation and spore germination in Dictyostelium discoideum. AB - Dictyostelium discoideum spores can be activated to initiate germination either endogenously via a diffusible autoactivator, or exogenously via heat. Following activation, three successive stages of germination occur, the lag stage, spore swelling and amoebal emergence. A previous study [Lydan M. A. and Cotter D. A. (1994) FEBS Lett. 115, 137-142] has shown that spore swelling is dependent on the activity of calmodulin. In this study, the calmodulin antagonists trifluoperazine and calmidazolium inhibited autoactivation, but had no effect upon heat activation. These agents also inhibited amoebal emergence following either form of activation. The effects caused by the anti-calmodulin agents were specific to an inhibition of calmodulin function since agents which modulate the activity of protein kinase C had no effect upon spore germination. A calcium-dependent calmodulin-binding protein of about 64,000 M(r) may be associated with the process of autoactivation since it was only seen in those spores which respond to the autoactivator. Overall, this study provides evidence to show that calmodulin plays a regulatory role during autoactivation and amoebal emergence during spore germination in D. discoideum and provides evidence for the calmodulin-dependent mechanisms which mediate each of these phases of germination. PMID- 7888303 TI - Potentiation by cholesterol and vitamin D3 oxygenated derivatives of arachidonic acid release and prostaglandin E2 synthesis induced by the epidermal growth factor in NRK 49F cells: the role of protein kinase C. AB - We have previously demonstrated that oxysterols and calcitriol potentiate arachidonic acid (AA) release and prostaglandin (PG) synthesis when NRK cells (fibroblastic clone 49F) are activated by foetal calf serum. As serum is essential for a full oxysterol effect, we hypothesized that these compounds could act on one or more of the events triggered by serum growth factor binding to their specific receptors and leading to PLA2 activation; we showed that the oxysterol effect on AA release is synergistic with, but not fully dependent on, protein kinase C (PKC) activity and Ca2+ ion fluxes, suggesting that oxysterols could effect early events in the cell signalling pathway. In the present paper, we investigated the effect of some oxysterols and calcitriol on epidermal growth factor (EGF)-induced AA release and PGE2 synthesis in NRK cells. The clear potentiation of EGF effect by most of the oxygenated sterols--chiefly when polyoxidized--cannot be explained by a modification of EGF high affinity binding site number which was only moderately increased after a 4 h incubation of cells with these compounds, and moreover was not related to the ability of a given oxysterol to increase PLA2 activity; whatever the compound, the dissociation constant (Kd) of either a high or low affinity binding site was unchanged (respectively, 3.5 x 10(-11) M and 4.4 x 10(-10) M). Genistein, a known inhibitor of EGF receptor tyrosine kinase, changed neither the EGF effect on AA release nor its potentiation by oxysterol, whereas it inhibited PGE2 synthesis in both situations. PKC activation by phorbol ester TPA increased the effect of EGF alone as well as the oxysterol potentiating effect, whereas PKC down-regulation strongly decreased both of these effects, showing that both are dependent on PKC activity. Nevertheless staurosporine, a PKC inhibitor, did not reproduce the effects of PKC down-regulation on EGF activation: stimulatory when AA release was induced by EGF alone, inhibitory when AA release is induced by TPA alone, this compound did not modify the oxysterol potentiating effect. In conclusion, the potentiating effect of oxysterols on AA release seems to be exerted downstream to the growth factor receptor (as demonstrated here with EGF) and probably at the PKC level, but not exclusively. PMID- 7888304 TI - Evidence for expression of a Ras-like and a stage specific GTP binding homologous protein by Plasmodium falciparum. AB - Plasmodium falciparum, the parasite responsible for the most severe form of malaria, undergoes an asexual multiplication in man and a sexual one in mosquito. The asexual cycle can be reproduced in vitro. The present work reports the isolation of a small guanosine triphosphate-binding protein in Plasmodium falciparum extracts. This protein, a 21,000 M(r) Ras-like molecule, was revealed by western blotting in each stage of the intraerythrocytic asexual life cycle. Conversely, a 46,000 M(r) G alpha subunit of a heterotrimeric GTP-binding protein was found to be expressed during a short period from mature schizonts to free merozoites. In order to provide additional evidence for the presence of these GTP binding proteins in Plasmodium falciparum cultures and also to determine the kinetics, we tested two toxins that are involved in the cellular signalling transduction. We observed that pertussis toxin increases P. falciparum growth, whereas cholera toxin induces crisis forms, and subsequent parasite death within the following 24 h. PMID- 7888305 TI - Increased proliferative activity, loss of beta-adrenergic receptor function and class I major histocompatibility complex antigen surface expression in a modified lymphoma cell line. AB - The molecular interaction of class I major histocompatibility complex (MHC) antigens (Ag) and of beta-adrenergic receptors was previously demonstrated on lymphocytes. By long-term culturing with high concentration of foetal calf serum, the murine S49 lymphoma cell line was modified (S49m) giving phenotypic alterations in beta-adrenergic receptors and class I Ag expression. S49m cells displayed a reduced number of beta-adrenergic sites that were uncoupled to the adenylate cyclase system. These were unable to respond to beta agonist stimulation, despite the fact that direct activation of Gs could be achieved with aluminium tetrafluoride. Although S49m cells showed normal expression of the thy 1.2 Ag, they displayed no expression of class I Ag of the d haplotype. This was assessed by the evident lack of cytotoxic activity of specific monoclonal antibodies (Mo Ab) and of their binding. When performing IFI staining on permeabilized cells, we found positive staining with anti-class d Ab inside the cell. This loss of expression and activity of beta-adrenoceptors and the internalization of class I Ag were accompanied by a higher rate of proliferation in S49m cells. The possibility that the loss of both molecules would modify the biology of the cell is also discussed. PMID- 7888307 TI - The importance of sexual rehabilitation after breast cancer treatment. PMID- 7888306 TI - Molecular cloning and expression, in both COS-1 cells and S. cerevisiae, of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1). AB - Screening a human T lymphocyte cDNA library with a phosphodiesterase (PDE) specific probe resulted in the isolation of two overlapping cDNA clones, h2.2 and h6.1, that encode a type IV, rolipram inhibited cAMP-specific PDE. Clones h2.2 and h6.1 were 1015 bp and 2288 bp in length, respectively, and overlapped for 984 bp with only one nucleotide difference. The h6.1 cDNA was extended at the 5'-end by 1304 bp, with respect to h2.2, and encoded an incomplete ORF (lacking an initiation codon) of 668 amino acids. The merged nucleotide sequence of h6.1/h2.2 exhibited 99.5% homology in the ORF (ten nucleotide changes resulting in six amino acid changes), and 95% homology in the 3'-untranslated region, with the previously reported human PDE-IVA cDNA [Livi G. P., Kmetz P., Mchale M. M., Cieslinski L. B., Sathe G. M., Taylor D. P., Davis R. L., Torphy T. J. and Balcarek J. M. (1990) Mol. Cell Biol. 10, 2678-2686]. The sequence reported for h6.1/h2.2 matched that found for IVA clones isolated from three other human cDNA libraries, a human genomic cosmid clone and pcr amplified products of the exon covering these differences in two individuals. The h6.1 cDNA was engineered to generate a complete ORF by building in the 56 bp, including the initiation codon, present in hPDE-IVA-Livi and missing from the 5'-end of h6.1, producing a cognate ORF encoding a protein of 687 amino acids but differing in five amino acids which lay in or adjacent to the putative catalytic domain. The complete h6.1 ORF was engineered for expression in both Saccharomyces cerevisiae and in COS-1 cells. Integration of a single copy of the engineered ORF of h6.1, under the transcriptional control of a constitutive yeast promoter, at the pep4 locus of a S. cerevisiae strain lacking both yeast PDE genes resulted in functional complementation of the yeast pde-phenotype. Yeast strains with functional PDE were a light creamy white colour, while strains devoid of PDE activity were a dull brown colour. Expression of h6.1 in COS-1 cells led to the production of a typical type IV PDE activity in that cAMP, but not cGMP, served as substrate and its activity was insensitive to either Ca2+/CaM or cGMP but was inhibited by low concentrations of rolipram.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7888308 TI - Genetic testing for cancer risk: research projects being funded. PMID- 7888309 TI - Ovarian cancer in the elderly patient. AB - Ovarian cancer is a disease of the elderly, with more than 50% of cases occurring in women over 65 years of age. Studies from national databases, reporting institutions, and cooperative groups conducting clinical cancer research indicate that elderly women with epithelial ovarian cancer have a worse prognosis than younger women. Elderly women present with more advanced cancers that are usually of high grade and with aneuploid DNA content. In contrast to younger patients, elderly women more frequently do not receive definitive chemotherapy or surgery and seemingly undergo less aggressive treatments. Age alone does not appear to be a risk factor for surgical morbidity or drug treatment toxicity. Research is needed regarding age-related genetic alterations in ovarian cancer. Clinical trials of ovarian cancer treatment in elderly women should include quality of life measurements, recognizing the specific functional and psychosocial expectations of this patient population. PMID- 7888310 TI - Report from the CDC. Minors' access to cigarette vending machines. PMID- 7888311 TI - "Immortalizing agent" of tumor cells found in yeast. PMID- 7888312 TI - Amenorrhea following chemotherapy for breast cancer: effect on disease-free survival. AB - Adjuvant chemotherapy, which is known to be a cause of premature ovarian failure, is now recommended for most women diagnosed with breast cancer, and it has been postulated that the effects of chemotherapy are of the same order as those of ovarian ablation. Thus, it is important to correlate disease-free survival with induction of early menopause. We examined the literature for papers reporting the effects of chemotherapy on menstruation and ovarian changes in premenopausal women. Few studies reported such effects, but of those papers reviewed here, no such benefits in terms of disease-free survival were found. Thus, the benefits of adjuvant chemotherapy must be carefully weighed against the risk of early menopause in premenopausal women with good prognosis breast cancer. PMID- 7888313 TI - Ipsilateral breast tumor recurrence following conservative surgery and radiation therapy. AB - Ipsilateral breast tumor recurrence occurs in approximately 10% to 15% of patients undergoing conservative surgery and definitive radiation therapy. Mammography alone detects one third of breast recurrences. Most recurrences are invasive, few demonstrate simultaneous distant metastasis, and approximately 40% have axillary lymph node involvement. Mastectomy is the standard salvage procedure. Axillary lymph node dissection may help guide adjuvant treatment as well as reduce the risk of a subsequent regional recurrence. The decision of whether to use adjuvant therapy should be based on tumor size, lymph node status, receptor status, DNA index, S-phase fraction, and disease-free interval. Ipsilateral recurrence may be an independent prognostic factor for distant metastasis. PMID- 7888314 TI - Phase II results using a new antibody in the treatment of lymphoma. PMID- 7888315 TI - Retrovirus delivers gene therapy to brain tumors. PMID- 7888316 TI - Index to nos. 1 to 51/52. PMID- 7888317 TI - Mental health: family counsel. PMID- 7888318 TI - A born leader. Interview by Graham Scott. PMID- 7888319 TI - Infant weaning: the COMA report. AB - The recent launch of a report on infant weaning offers health visitors and nurses a blueprint for advising parents on this crucial stage in child development. This article looks at some of the main recommendations of the report, and sets out the implications for nursing. PMID- 7888320 TI - Counting the cost of stress in nursing. PMID- 7888321 TI - Complementary therapy. The use of touch in nursing practice. AB - Touching patients seems a natural and integral part of nursing care, but do nurses really understand the potential benefits and potential harm touch can cause patients? The authors look at the importance of touch in nursing care, and suggest that greater awareness of how touch affects patients would be of benefit to nurses. PMID- 7888322 TI - Perceptual problems in thyroid eye disease. AB - Graves' disease affects the individual in many significant ways, but perhaps the most immediately obvious is its effect on the eyes. The author explores how exophthalmus and proptosis associated with the disease can create not only physical and perceptual difficulties for the patient, but also complicated problems with social interaction, self-image and psychological functioning. PMID- 7888323 TI - Right to nurse. Doing it for ourselves. PMID- 7888324 TI - One minute wisdom. Performance related pay. PMID- 7888325 TI - AIDS focus. Communicating with parents. PMID- 7888326 TI - AIDS focus. Altered body image. PMID- 7888327 TI - Popular and effective. Interview by Graham Scott. PMID- 7888328 TI - Health of the nation: missing the target. PMID- 7888329 TI - Nurses and the law. A growing band of expert witnesses. PMID- 7888330 TI - Primary nursing: a partnership in Broadmoor. PMID- 7888331 TI - Practice nursing: a study of the role. AB - The author used a questionnaire survey to elicit the views of practice nurses in Lothian on their role. While the sample was small, the results reveal interesting data on the nurses' perceptions of what is most important about work, relationships with patients and GPs, and training needs. PMID- 7888332 TI - Adolescents' views of outpatient services. AB - This study used a qualitative, inductive method to seek out the perceptions of adolescents using the children's outpatient service in one general hospital. The views of seven young people attending clinics for chronic problems were obtained through taped, unstructured interviews. Four themes emerged which may give valuable insights into the needs of this age group in an outpatient setting. Implications for practice are discussed. PMID- 7888333 TI - First aid: essential skills for nurses. AB - This article focuses on the development of first aid content in the Project 2000 curriculum in one college of nursing. It also reviews literature relevant to the nurse's legal, professional and moral duties to give first aid. The development and evaluation of a pilot first aid course for Project 2000 students is described, followed by an outline of future plans. PMID- 7888334 TI - Dementia in acute units: confusion. AB - This is the fifth article in our series which looks at how nurses in acute units can manage the behaviour problems posed by people with dementia. The focus this month is on post-operative confusion, with the author discriminating between it and other forms of confusion, and offering sensible guidelines for management. PMID- 7888335 TI - Right to nurse. Tell me a story. PMID- 7888337 TI - Ethics: the last execution. PMID- 7888336 TI - One minute wisdom. Health economics is nothing more than an excuse for cost cutting. PMID- 7888338 TI - Ethics: turn out the light. PMID- 7888339 TI - Change: Val Doonican rocks, but does nursing? PMID- 7888340 TI - Dieting: media watch. PMID- 7888341 TI - Corruption: greasy palms. PMID- 7888342 TI - Clinic for gay men opens at Guy's. Interview by Kate Williams. PMID- 7888343 TI - Community care: poverty and old age. PMID- 7888344 TI - Women's issues: a neglected majority. PMID- 7888346 TI - Cervical cancer: improving the service. AB - Cervical cancer is a major cause of morbidity and mortality, but critics of the cervical cancer screening programme claim not enough is being done to prevent and treat the illness. In particular, the programme has been criticised for failing to target the most appropriate groups of women. The author reviews the current unsatisfactory situation, and suggests possible ways forward. PMID- 7888345 TI - Ethnic minorities: running a band-aid service. PMID- 7888347 TI - Nursing developments: trust nurses' views. AB - Innovations in nursing require strong management. In this survey, the author sought the views of trust nurse executives on how the ideas of the UKCC's The Scope of Professional Practice and clinical supervision could be implemented. The results provide food for thought for nurses at all levels. PMID- 7888348 TI - Service provision for severe mental illness. AB - With the move to provide care in the community for mentally ill people, this article argues that the needs of those people with challenging behaviour are not being adequately met. The author looks at the reasons and the implications of insufficient resources for this group of people, and explores some possible solutions. PMID- 7888349 TI - Sleeping it off. PMID- 7888351 TI - Community: war on the weak. PMID- 7888350 TI - Performance-related pay--a false idol? PMID- 7888352 TI - Support workers: unsung heroes. PMID- 7888353 TI - Ethics: sharing to care. PMID- 7888354 TI - Antineutrophil cytoplasmic antibodies and their relevance to the dermatologist. AB - The term vasculitis embraces a heterogeneous group of conditions which may occur as primary phenomena or secondary to disorders such as rheumatoid arthritis or systemic lupus erythematosus. Classification of vasculitis is often difficult in the absence of identifiable aetiological factors or specific serological markers. However, the primary systemic vasculitides can be segregated morphologically, according to the size of blood vessels involved and the presence of granulomata (Table 1). Recently, the discovery of circulating antineutrophil cytoplasmic antibodies (ANCA) in many patients with these disorders, whose differing specificities substantiate the histological classification, has led to interest being focused on their relevance in the development of vasculitis. This paper reviews the historical aspects of the detection of ANCA, and the value of these antibodies in the diagnosis and management of the primary systemic vasculitides likely to be encountered by the dermatologist. The clinical features in patients with these vasculitides are also outlined. PMID- 7888355 TI - The association between lichen sclerosus and antigens of the HLA system. AB - Although frequently linked clinically with autoimmune disease, no immunogenetic basis for lichen sclerosus has ever been established. In this study, we examined in detail the HLA antigens of 84 patients with histologically proven disease, compared with 357 controls. Patients with lichen sclerosus did not have the expected HLA A1, B8, DR3, DQ2 autoimmune profile. Instead, DQ7 was present in 39 of 78 (50%) of patients compared with 89 (25%) controls (P < 0.001). In addition, 61 of 78 patients (78%) had either DQ7, DQ8 or DQ9 antigens, or a combination of these, compared with 142 (40%) controls (P < 0.01). Raised levels of DQ7 correspond to a glutamic acid residue at position 45 of the DQB1 locus. Proline amino acids at position 55 of this DQB1 locus could explain the raised levels of DQ7, 8 and 9, and exert a secondary effect. There is preliminary evidence that the immunogenetic profile of patients with this disease may affect disease expression with regard to site and extent of involvement. PMID- 7888356 TI - The short-term treatment of acne vulgaris with benzoyl peroxide: effects on the surface and follicular cutaneous microflora. AB - A 28-day treatment regimen was undertaken by 12 volunteers, in which 5% (w/v) benzoyl peroxide (BP) in an aqueous gel was applied daily to the entire face. Clinical efficacy of the treatment was assessed after 2, 4, 9, 14 and 28 days, and the surface and follicular microbial populations were enumerated using established techniques. Viable counts were obtained for propionibacteria and Micrococcaceae. Mean numbers of propionibacteria recovered from the skin surface and follicular casts were significantly reduced after 2 days' treatment (P < 0.01), and the population was maintained at a significantly lower level throughout the study (P < 0.01), with mean values approaching the lower detection limit of the assay. Significant reductions in the surface and follicular Micrococcaceae were observed after 2 days' treatment, and at all subsequent visits (P < 0.05). After 2 days' treatment, only slight reductions in mean acne grade and mean inflamed lesion count were observed. However, at all subsequent visits the mean acne grade was significantly reduced (P < 0.05) compared with T0. The mean non-inflamed lesion count was lower than the pretreatment level at all visits, although the results were variable. The results indicate that significant reductions in surface and follicular microorganisms may be obtained after 48 h treatment with BP. Therefore, the non-specific antibacterial action of BP may be utilized in short intervening courses to reduce the carriage of antibiotic resistant micro-organisms and thus improve the long-term efficacy of antibiotic acne treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888357 TI - Clinical relevance of sonometry-derived tumour thickness in malignant melanoma--a statistical analysis. AB - High-frequency sonography has been shown to be a useful tool in planning operative strategy in the surgery of malignant melanoma (MM). The purpose of the present study was to compare sonometric and histometric data of tumour thickness in primary cutaneous MM, applying statistical methods in order to evaluate the pre-operative relevance of sonometry. The thickness of 259 melanomas was measured preoperatively by a 20-MHz B scan, and postoperatively by histometry. Statistical analysis was performed using Pearson's correlation coefficient and absolute and relative differences. Although the correlation between sonometry and histometry was good (r = 0.88), there was a mean difference of 0.39 mm (relative difference 28%). Overall, sonometry was in agreement with the corresponding histological classes in 75% of cases. However, tumours assessed by ultrasound as between 0.55 and 0.95 mm thick were incorrectly classified according to histology in 34%, and those between 1.30 and 1.70 mm were incorrectly classified in 50% of cases. Our data reveal greater differences between sonometry and histometry using appropriate statistical methods. A concept to assess differences between sonometry and histometry is recommended. PMID- 7888358 TI - Teaching non-dermatologists to examine the skin: a review of the literature and some recommendations. AB - An international committee has recently decided on standard definitions of common dermatological terms. However, some inconsistencies remain. Those concerning the definitions of 'plaque' and 'patch' could be resolved by making the lower limit of size of these lesions 0.5 cm, to correlate with the proposed 0.5 cm upper limit of size of a macule and a papule. The practice of describing crust, scale, etc. as secondary lesions should be abandoned. Instead, the type of lesion (e.g. papule, plaque, nodule), and its surface features (e.g. scale, crust, etc.) should be described separately. The concept of smooth/normal as a surface feature should be included. A scheme is recommended for describing skin lesions, which is based on the following features: (i) their site, distribution and arrangement; (ii) lesion morphology, under the following headings: palpation, type, surface, colour, border, size, shape; and (iii) associated features, such as changes affecting the nails, mouth, scalp and genitals. PMID- 7888359 TI - Dermatology in the intensive care unit. AB - We report our experience, and review the literature, concerning 'intensive care dermatology'. Over a period of 14 months, 27 patients who had significant cutaneous problems were seen in the intensive care unit. These included primary dermatological conditions, multisystem disorders with cutaneous signs, complications of dermatological therapy, and skin conditions developing as complications of intensive care. We discuss the diagnosis and management of dermatological problems in the intensive care unit. PMID- 7888360 TI - The effect of severe psoriasis on the quality of life of 369 patients. AB - The aim of this survey was to quantify the level of handicap experienced by patients with severe psoriasis, and to assess the value that patients place on their disease using various questionnaire techniques. Dermatologists throughout the U.K. each gave a questionnaire to up to five psoriasis patients, who were either being admitted for in-patient care or were starting systemic therapy. Three hundred and sixty-nine questionnaires were completed. Of the 150 patients currently working, 59.3% had lost a mean of 26 days (SD 21.9) from work during the preceding year because of their psoriasis, and of the 180 not working 33.9% attributed not working to their psoriasis. The mean Psoriasis Disability Index (PDI) score was 38.2% (SD 23.3, n = 248), with the mean sub-scores of the 'daily activities' and 'treatment' sections being greater than those of the other three sections. Despite having severe psoriasis, the majority of patients felt that it would be worse to have diabetes, asthma or bronchitis than to have psoriasis. Forty-six, 42 and 32% considered it would be either 'better' or 'the same' to have diabetes, asthma or bronchitis, respectively. However, in those patients who also had the comparative disease, 87, 80 and 77% considered it would be 'better', or 'the same' to have the comparative disease. Forty-nine per cent of patients (n = 362) stated they would be prepared to spend 2 or 3 h each day on treatment if this might result in normal skin for the rest of the day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888361 TI - Reflectance spectrophotometry in the objective assessment of dye laser-treated port-wine stains. AB - At present, the treatment of choice for congenital capillary malformations of the port-wine stain type (PWS) is the flashlamp pulsed dye laser. Good results can be obtained in the majority of patients with this technique, but there is a group of poor responders. In the search for predictive tools to determine the therapeutic outcome, we have used a new photoelectric reflectance instrument. Sixty-six patients with PWS, mainly on the face, were treated with a pulsed dye laser during a 21-month period. Using a hand-held reflectance photometer, erythema indices were obtained for the PWS and normal skin. Based on these indices, a relative blanching effect could be calculated. The therapeutic result was judged to be excellent in 19, good in 20, fair in 14 and poor in 13 patients. There was a good correlation (r = 0.844) between the degree of blanching and the therapeutic result. In the 'excellent' category, an average blanching effect of 47% was present after the first treatment, and this increased to between 75 and 100% after successive treatments. In the 'poor' category, the blanching effect after one treatment averaged 14%, increasing to only 40% after up to six treatments. It thus seems to be possible to predict the outcome of therapy, which is of considerable help in treatment planning. Reflectance measurements, an objective estimate of blanching, correlate well with the clinical results, and are helpful in monitoring and predicting the therapeutic outcome in dye laser treated PWS. PMID- 7888362 TI - Melanoma awareness and sun exposure in Leicester. AB - The city of Leicester, in conjunction with other centres throughout the U.K., was targeted for publicity about melanoma over a 3-year period from 1987 to 1989. We report the results of a survey to assess the level of awareness of melanoma, and to document current sunbathing practices subsequent to that period. The general level of awareness of melanoma in the community was good (74%). People who knew about melanoma were more likely to use a sunscreen at home and abroad (odds ratios 1.63, 95% CI 1.19-2.24 and 1.39, 95% CI 1.03-1.86), but paradoxically more likely to sunbathe than those who had never heard of melanoma (odds ratio 1.33, 95% CI 1.03-1.72). Females were more knowledgeable than males (odds ratio 1.74, 95% CI 1.26-2.22), but continued to sunbathe. Teenagers and young adults tended to be relatively ignorant of melanoma, and were less likely to protect themselves against sunburn while sunbathing than other age groups. Teenagers, young adults, and males need to be targeted more effectively in future publicity campaigns. Furthermore, many people who know about melanoma continue to put themselves at risk by sunbathing. New strategies need to be developed to influence behaviour as well as increasing awareness. PMID- 7888363 TI - Cimetidine improves the therapeutic/toxic ratio of dapsone in patients on chronic dapsone therapy. AB - We have previously shown that cimetidine, given concurrently for 2 weeks to patients on chronic dapsone therapy, reduced methaemoglobinaemia by inhibiting the formation of the toxic hydroxylamine metabolite of dapsone. The aim of the present study was to examine the effect of this combination on the benefit/toxic ratio of dapsone over a longer period. Eight patients (six dermatitis herpetiformis, one linear IgA disease, one folliculitis decalvans) on long-term dapsone 50-100 mg daily, took cimetidine 1.6 g daily concurrently for 3 months. At 3-weekly intervals, a clinical assessment was made, plasma dapsone and methaemoglobin were measured, and parameters of oxidative haemolysis were monitored. The dapsone level rose from 2298 +/- 849 ng/ml (mean +/- SD) at baseline to 3006 +/- 1131 ng/ml at week 3 of cimetidine (P < 0.01). This rise in plasma dapsone was sustained during cimetidine administration, falling to 2446 +/ 954 ng/ml when cimetidine was stopped (P < 0.02). The methaemoglobin fell from 5.5 +/- 2.2% (mean +/- SD) at baseline to 3.9 +/- 1.1% at week 3 (P < 0.01), and remained low until week 12, when there was a return to baseline values (P < 0.01). The haemoglobin did not change from the baseline of 12.7 +/- 0.3 g/dl (mean +/- SD), and other parameters of haemolysis were unaltered. There was a fall in the visual analogue score for headache (P < 0.05), but this was not associated with any deterioration in control of the skin disorders. Hence, long term concurrent cimetidine results in increased plasma dapsone levels without increased haemolysis, and is accompanied by reduced methaemoglobinaemia for more than 2 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888364 TI - Cutaneous infiltration in T-cell prolymphocytic leukaemia. AB - T-cell prolymphocytic leukaemia (T-PLL) is an aggressive leukaemia accounting for over 30% of all mature T-cell malignancies. We describe the clinical manifestations and histology of cutaneous involvement in a series of 92 patients with T-PLL. Of the 92 patients, 26 (28%) had cutaneous involvement, and in 23 this was present at the time of the diagnosis of the leukaemia. Skin manifestations included a diffuse infiltrated erythema, infiltration localized to the face and ears, nodules and erythroderma. Histology showed a perivascular and periappendageal dermal infiltrate of lymphoid cells with the morphology of prolymphocytes. An early skin biopsy in these patients should help to reveal the underlying diagnosis. PMID- 7888365 TI - A double-blind, placebo-controlled trial of continuous acyclovir therapy in recurrent erythema multiforme. AB - Twenty patients who suffered from more than four attacks of erythema multiforme (EM) per year were enrolled in a 6-month double-blind, placebo-controlled trial of acyclovir 400 mg twice daily. Fifteen patients had disease precipitated by recurrent herpes simplex. In the acyclovir-treated group the median number of EM attacks during the treatment period was zero, compared with three in the placebo treated group (P < 0.0005, Wilcoxon rank sum test). Seven of the 11 patients treated with continuous acyclovir did not have any attacks of EM while taking the drug, and one showed almost complete disease suppression. Following treatment with acyclovir, two patients went into complete remission, whereas all individuals in the placebo group continued to have attacks. In the acyclovir treated group nine of the 11 patients had herpes simplex-precipitated disease. One of the two patients with idiopathic disease showed complete disease suppression while on acyclovir, lending support to the view that idiopathic recurrent EM may be related to subclinical herpetic infection. In this study, we have shown that continuous acyclovir therapy can completely suppress attacks of recurrent EM and, in some cases, may induce disease remission. PMID- 7888366 TI - British Photodermatology Group Workshop. Predictive in vitro methods for identifying photosensitizing drugs: a report. PMID- 7888367 TI - Calcinosis cutis following liver transplantation: a complication of intravenous calcium administration. AB - Calcinosis cutis may be a complication of administration of intravenous calcium solutions. We report four patients who developed calcinosis cutis following orthotopic liver transplantation, all of whom had received calcium chloride solutions intravenously during surgery. There was no evidence of extravasation of the solutions. A gradual improvement of the lesions was seen in the subsequent months. This complication of intravenous calcium infusions is probably related to the large amounts of blood-derived products and of calcium salts administered during surgery. PMID- 7888368 TI - Erosive pustular dermatosis of the leg. AB - Two women with a distinctive rash on the legs are reported. The clinical features of erythema, erosions, crusting and pustular lakes, and the failure to respond to any treatment except very potent topical corticosteroids (Dermovate), are very similar to those of erosive pustular dermatosis of the scalp. PMID- 7888369 TI - Livedo reticularis associated with hereditary protein C deficiency and recurrent thromboembolism. AB - We report the occurrence of livedo reticularis in a patient with symptomatic hereditary type 1 protein C deficiency. Antithrombin III deficiency and the antiphospholipid syndrome may also be associated with livedo reticularis, and we suggest that a thrombophilia screen may be a useful investigation in a patient with otherwise unexplained livedo, particularly if there is a personal or family history of thromboembolism. PMID- 7888370 TI - Diffuse plane xanthomatosis and acquired palmoplantar keratoderma in association with myeloma. AB - We report a patient with diffuse plane xanthomatosis, acquired palmoplantar keratoderma, and myeloma. Although diffuse plane xanthomatosis is a recognized manifestation of paraproteinaemia, keratoderma is not. However, successful treatment of the myeloma in our patient coincided with a dramatic improvement in the keratoderma, suggesting a genuine association between the two disorders. PMID- 7888371 TI - Peripheral T-cell lymphoma involving subcutaneous tissue. AB - The peripheral T-cell lymphomas, presumably derived from various immunocompetent peripheral T-cell system components, form a heterogeneous group of non-Hodgkin's lymphomas. We describe two patients with peripheral T-cell lymphoma primarily involving subcutaneous tissue. They presented with multiple subcutaneous nodules. Skin biopsy specimens in both patients demonstrated a lobular subcutaneous infiltrate. The infiltrate consisted of small and medium-sized atypical lymphoid cells. Both patients had a protracted clinical course before they were diagnosed as having malignant lymphoma. We detected latent Epstein-Barr virus infection in the skin lesions of case 2. Latent Epstein-Barr virus infection might be related to the development of this variant of peripheral T-cell lymphoma. PMID- 7888372 TI - Eosinophilic pustular folliculitis in infancy: report of two affected brothers. AB - We describe two brothers with eosinophilic pustular folliculitis. Both had recurrent crops of papules and pustules, primarily affecting the scalp. The eruption began in the neonatal period. Both children had a leucocytosis with eosinophilia. Histology revealed folliculitis, with an infiltrate in which eosinophils were predominant. Bacteriological and fungal cultures of pustules were negative. There was a good clinical response to treatment with a topical corticosteroid and dapsone. We review the 28 previously reported cases of eosinophilic pustular folliculitis in infancy. The occurrence of this disorder in brothers suggests that an inherited or contagious factor may be involved in its aetiology. PMID- 7888373 TI - Mycobacterium bovis-BCG infection of the glans penis: a complication of intravesical administration of bacillus Calmette-Guerin. PMID- 7888374 TI - Role of recurrent oral candidiasis associated with lingua plicata in the Melkersson-Rosenthal syndrome. PMID- 7888375 TI - Polymyositis and malignant melanoma. PMID- 7888376 TI - Sneddon-Wilkinson disease in association with rheumatoid arthritis. PMID- 7888377 TI - Pemphigus vulgaris induced by captopril. PMID- 7888378 TI - Tetracycline phototoxicity. PMID- 7888379 TI - Coexistence of generalized milia and naevus depigmentosus. PMID- 7888380 TI - Achenbach syndrome. PMID- 7888381 TI - Stroke in young adults: a retrospective analysis. AB - Recent data suggest that stroke in young adults is more frequent than previously reported. To explore clinical and discharge characteristics of young adults with stroke, a retrospective chart review was completed for all young adults (ranging from 18 to 45 years of age, inclusively) admitted to this institution in 1992 with a diagnosis of stroke. The group consisted of 37 patients (mean age 36 years). The 16 men and 21 women represented 8.4% of the 441 patients with stroke treated in 1992. A total of 25 (67.6%) had ischemic strokes (37.8% cerebral infarction and 29.8% transient ischemic attacks), and 12 (32.5%) had hemorrhagic strokes (18.9% subarachnoid and 13.4% intracerebral hemorrhage). The distribution of cerebral infarction/transient ischemic attack subtypes included 16% atherothromboembolic, 32% cardiogenic, 4% lacunar, 16% other causes (such as migraine or vasculitis), and 32% of undetermined cause. Hemorrhagic stroke subtypes included 25% hypertensive, 41.6% aneurysmal, 16.7% other vascular anomalies (such as arteriovenous malformations), and 16.7% of undetermined cause. Among those who survived, 88% were discharged directly home, and 12% required rehabilitation. During the acute phase, 11% of the population died. These data suggest that strokes in young adults (1) are more frequent than previously recognized, (2) have multiple etiologic and pathologic factors, and (3) in many cases, are treatable. In general, these patients have a good prognosis. PMID- 7888382 TI - Use of the intermittent pneumatic compression device in venous ulcer disease. AB - The intermittent pneumatic compression device is a relatively new treatment for patients with venous ulcers. With the advent of this therapy being used by the patient in the home setting, the nurse is the primary point of contact for patient questions, concerns, and patient education. Nurses need to know the optimal compression pressure, inflation time, and sequencing time cycles to advise patients in the proper use of this therapy and how to screen patients for its safe use. The major contraindication for this therapy is the presence of deep venous thrombi. A review of the literature is presented, concluding with a recommended scientific basis for optimal compression pressure, inflation time, and sequencing time cycle pattern for the intermittent pneumatic sequential compression device in the venous ulcer patient population. Patient education strategies and topics are discussed. PMID- 7888383 TI - The perspective of patients with vascular disease on participation in clinical trials. AB - Very little objective data are available concerning the patient's perspective on clinical trial participation. Participants from the Asymptomatic Carotid Atherosclerosis Study and Clopidogrel vs. Aspirin in Patients at Risk for Ischemic Events Trial were personally interviewed by the nurse coordinator to document their views. A questionnaire including both closed-ended and open-ended questions was used. The main advantages to participation in a study were close follow-up and the opportunity for improved health. More than half of the subjects saw no disadvantages to participation. The physician was the primary motivator for entering trials. Most patients expressed an interest in future study participation. PMID- 7888384 TI - Advanced practice nursing in the acute care setting. PMID- 7888385 TI - Spontaneous subclavian venous thrombosis. PMID- 7888386 TI - An update on the cause of abdominal aortic aneurysms. AB - Historically the most common cause of abdominal aortic aneurysms has been attributed to atherosclerotic degeneration of the vessel wall. However, over the last decade this widely accepted theory has been challenged by a substantial body of research that proposes that atherosclerosis is more likely to be an associated finding rather than an instigating factor. Arguments against an atherosclerotic theory are supported by differences in the characteristics of atherosclerotic occlusive disease and aneurysmal disease. Emerging theories propose that development of abdominal aortic aneurysms involves genetic factors and fundamental structural changes in the aorta. The purpose of this article is to review these emerging theories and discuss their implications on patient treatment. PMID- 7888387 TI - Prognostic factors in children with supratentorial (nonpineal) primitive neuroectodermal tumors. A neurosurgical perspective from the Children's Cancer Group. AB - Supratentorial primitive neuroectodermal tumors (S-PNETs), which have also been called cerebral neuroblastomas, have been considered to be the hemispheric equivalent of posterior fossa medulloblastomas. Twenty-seven children with S PNETs (excluding pineoblastomas) which were confirmed by central pathology review were treated on the CCG-921 protocol from 1986 to 1992. After operation, all patients were staged with CSF cytology and spinal myelography or magnetic resonance scans and were treated with craniospinal irradiation and chemotherapy. Data from these 27 patients have been reviewed to evaluate neurosurgical treatment, survival, and prognostic variables that correlate with survival. Overall survival at 5 years was 34% (SE 20%) and progression-free survival (PFS) was 31% (SE 18%), which is lower than the survival of patients with posterior fossa PNETs (medulloblastomas). PFS was significantly worse in children 1.5-3 years of age at diagnosis and in those with evidence of tumor dissemination at the time of diagnosis. Large preoperative tumors were more likely to be associated with greater than 1.5 cm2 residual tumor postoperatively. Neurosurgeons estimated that less than 1.5 cm2 of residual tumor was present in 52% of the cases; postoperative scans confirmed that in 58%. For children with less than 1.5 cm2 residual tumor, postoperative survival at 4.0 years was 40% (SE 22%); for those with greater than 1.5 cm2 residual tumor, survival was 13% (SE 8%). The difference did not reach statistical significance, due to small numbers in this series, though a trend did exist (p = 0.19). Large series will be required to clarify the effects of extent of resection on survival. PMID- 7888389 TI - Agenesis and dysgenesis of the sacrum: neurosurgical implications. AB - We reviewed 27 patients with congenital anomalies of the sacral spine. There were 16 males and 11 females with a mean follow-up of 81.1 months (range 8-211 months). Fifteen patients had sacral agenesis and 12 had sacral dysgenesis. Fifteen patients had neuroimaging of the spine. Seven patients had conus termination below the L2 vertebral body. Four patients had associated thoracic syringomyelia and 6 patients were identified with caudal or dorsal lipoma. There were only two episodes of neurological deterioration, both in a single patient who had a lipomyelomeningocele, in 182 patient-years of follow-up. Four patients with low lying conus had pre-emptive spinal cord exploration for release of tethering in order to prevent neurological deterioration. Patients with agenesis or dysgenesis of the sacrum should undergo magnetic resonance (MR) imaging of the spine in order to detect spinal cord lesions associated with progressive neurological deterioration. Findings on MR imaging are more likely to correlate with clinical course than findings on skeletal radiography. PMID- 7888388 TI - Pediatric traumatic intracranial aneurysms. AB - During the past 17 years, 7 children have been treated at Children's Hospital Los Angeles (CHLA) for traumatic intracranial aneurysms. These patients presented with subarachnoid or intraparenchymal hemorrhage (5 cases), growing fracture (1 case), and behavioral change (1 case). All patients were managed with surgery, and no patient died or was made neurologically worse as a result of such management. The existence of a traumatic aneurysm should be considered when new neurological symptoms develop in a patient with a history of head injury. PMID- 7888390 TI - Surgical management of the cloverleaf skull deformity. AB - The cloverleaf skull deformity, or Kleeblattschadel, is a rare malformation caused by synostosis of multiple cranial sutures. This anomaly has been reported to carry a dismal prognosis both in terms of neurological outcome as well as cosmetic appearance if treatment is delayed. Due to the paucity of data concerning the results of early operative intervention, it remains uncertain whether aggressive craniofacial decompressive/reconstructive procedures are effective in ameliorating the effects of the malformation on both neurological development and cosmetic appearance. This paper reports the treatment and outcome of 7 children with the cloverleaf skull malformation treated at our institution between 1981 and 1993. All children underwent an initial decompressive craniectomy with the removal of at least 50% of the cranial vault for relief of high intracranial pressure in early infancy. Our first 4 patients underwent near total calvariectomy whereas the 3 children treated subsequently have undergone a staged approach with anterior followed by posterior craniectomies with bone morcellation and replacement. Subsequent reconstructions, intended to further improve the cosmetic appearance, were performed later in infancy or in early childhood. Follow-up ranges from 17 months to 9 years, with a mean of 61 months. Long-term results are reported with regard to neurological outcome as well as normalization of skull shape in terms of both the cephalic indices and general cosmetic appearance. Of the 4 children initially treated with total calvariectomy, only 1 child is neurologically normal and has a good cosmetic appearance. One child is severely impaired neurologically following a sagittal sinus thrombosis suffered during a secondary reconstructive procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888391 TI - Surgical treatment of moyamoya syndrome in children. 1985. PMID- 7888392 TI - Sarcomas in the central nervous system of children. 1982. PMID- 7888394 TI - The role of insight in exploratory psychodynamic psychotherapy. AB - Psychoanalytic theory holds that dynamic insight is used for self-observation and self-analysis during and after explorative therapy. Such self-analysis is held to lead to stable dynamic change. Within a sample of 43 moderately disturbed out patients, pre-treatment level of insight was associated with treatment length, with not being an early or late drop-out, and with receiving additional psychotherapy during a four-year follow-up period. Pre-treatment level of insight turned out to be not directly correlated with outcome two and four years after therapy. However, level of insight was significantly correlated with outcome in interaction with treatment length. Gain of insight measured at two-year follow-up was the strongest predictor of overall dynamic change four years after therapy, compared with all the other outcome assessments made at two-year follow-up. PMID- 7888393 TI - Comparison of gadolinium-enhanced MR and thallium-201 single photon emission computed tomography in pediatric brain tumors. AB - Despite its usefulness in adults with cerebral gliomas, indications for thallium 201 single-photon emission computed tomography (SPECT) in pediatric brain tumor patients are not well defined. We prospectively compared thallium SPECT with gadolinium-enhanced MR (Gd-MR) to determine if thallium SPECT provides clinically useful information that cannot be derived from Gd-MR. We studied 24 pediatric brain tumor patients, 7 at presentation and 17 during therapy. MR imaging included T2 and pre- and postgadolinium T1 images. Thallium SPECT was done within 48 h of MR imaging; thallium indices were calculated for 12 of 14 lesions which showed thallium uptake. Surgery and/or clinical follow-up are available in all patients. The tumors included pilocytic astrocytoma (7), medulloblastoma (5), brainstem glioma or glioblastoma (4), germinoma (3), optic glioma (2), mixed glioma (1), primitive neuroectodermal tumor (1), and choroid plexus carcinoma (1). Among the primary tumors, compared to MR, thallium SPECT was false-negative for tumor in 1 patient and true-positive in 6 patients. Among the patients studied while on therapy, compared to MR, thallium SPECT was true-negative for tumor in 7, true-positive in 5, false-negative in 3, and false-positive in 2. In both groups of patients, thallium SPECT underestimated tumor burden as nonenhancing regions of the tumors were not thallium-avid. Thallium indices did not correlate with histologic grade, biologic aggressiveness, or tumor type. We were unable to establish indications for the use of thallium SPECT in this setting as there was little clinically useful information derived from thallium SPECT that was not provided by Gd-MR. PMID- 7888395 TI - The relationship between ward atmosphere and staff attitude to treatment in psychiatric in-patient units. AB - The relationship between staff ratings of ward atmosphere, their attitude to treatment, and their direction of interest was investigated in four psychiatric in-patient units. Two general admission units, one intensive care unit, and one regional secure unit were studied. Fifty-eight psychiatric nurses rated their units using the Ward Atmosphere Scale-Form R (WAS) and expressed their direction of interest and attitude to treatment on the Direction of Interest Questionnaire and the Attitude to Treatment Questionnaire from the Claybury Selection Battery. An equamax factor analysis of the WAS subscales produced three clear factors. These factors, together with the original WAS subscales, were used to compare staff ratings of their units and to correlate with their attitude to treatment and direction of interest. A multivariate analysis of variance showed that staff ratings of ward atmosphere varied according to their unit and their attitude to treatment, but not with their direction of interest. Significant relationships were also found between staff characteristics, such as age, qualifications and experience, and ratings of ward atmosphere. PMID- 7888396 TI - Psychological distress and neuroticism: a two-wave panel study. AB - The temporal relationship between psychological distress and Neuroticism, both measured at two points eight months apart, was examined in a representative sample of 225 adult residents in Canberra, using cross-lagged panel correlation and latent variable LISREL analysis. Psychological distress was assessed by the 30-item General Health Questionnaire (GHQ-30). Because the synchronous and autocorrelations differed significantly, the interpretation of the significant difference between the cross-lagged correlations was problematic. The cross lagged path coefficients in the LISREL models were not significantly positive, suggesting that the temporal relationship between these two variables was spurious and due to error variance. The test-retest correlation was significantly higher for Neuroticism than for the GHQ-30, implying that Neuroticism is more a measure of a relatively stable personality characteristic and the GHQ-30 more one of transient psychological distress. PMID- 7888397 TI - Maternal dominance and the conception of sons. AB - Previous research (Grant, 1990, 1992) suggests that the sex of the infant is linked to maternal dominance, although it is unclear from existing studies whether women have obtained higher dominance ratings merely as a consequence of already carrying a male foetus. In an effort to overcome this problem, self report personality measures of dominance were completed by mothers of one- and two-year-old infants before they became pregnant again. In two independent studies (during 1983-84 and 1990-91), women who later conceived male infants scored significantly higher on dominance than those who later conceived female infants. The results of an analysis of all studies (N = 6) done on this topic (1969-91), are also presented, as are the results of an analysis of the four studies in which subjects were either not pregnant or were eight weeks pregnant or less. In both the combined analyses, those women who later bore sons were significantly more likely to have scored higher on the tests of dominance than those who later bore daughters (chi2 p < .0001). PMID- 7888398 TI - Retraumatization of Holocaust survivors during the Gulf War and SCUD missile attacks on Israel. AB - The purpose of this work was to study the reaction to a new threat and a new trauma of people severely traumatized in the past, when the new trauma had associations with the original one caused by the Holocaust. The situation created during the Gulf War gave a rare occasion to study it. We also wanted to check if the reaction of Holocaust survivors to the war differed from that of the general population. In addition we wanted to find out if there was a difference in reaction to the war between two clinical populations: Holocaust survivors and patients who are not Holocaust survivors. Sixty-six Holocaust survivors living in Israel, 31 of them undergoing psychiatric or psychological treatment either as in patients or as out-patients, were interviewed during the Persian Gulf War. In addition to the clinical group, there was a non-clinical group of 35 Holocaust survivors--21 whose homes were not damaged by SCUD missiles, and 14 whose homes were damaged by missiles. Those whose homes were damaged by SCUD missiles were retraumatized, and showed reactivation or exacerbation of the survivor syndrome. Six of them displayed the full syndrome of PTSD. PMID- 7888399 TI - Children in war: a silent majority under stress. AB - To assess the amount of stress exposure and reactions among children following a war situation, two comparative groups of non-displaced (N = 64) and displaced children (N = 70) from Croatia were administered a modified version of the War Trauma Questionnaire as well as the Impact of Event Scale (IES). The results showed that a majority of the children had been exposed to armed combat, with displaced children significantly more exposed to destruction of home and school as well as to acts of violence, and loss of family members, than the non displaced children. Regarding the IES scores, displaced children had significantly higher scores for the total score and for the intrusion and avoidance subscales. For girls the total score and intrusion score were significantly higher than for boys. Different exposure factors were significantly related to the IES scores, especially for the intrusion subscale of the IES. PMID- 7888401 TI - Vulnerability to respiratory infection and the four-day desirability dip: comments on Stone, Porter & Neale (1993). PMID- 7888402 TI - The implications of jumping on nursing bandwagons--the case of nursing models in Newfoundland hospitals. AB - Nurses are as susceptible as others to trends and fads which have an unproven impact on the provision of quality health care. One enduring trend has been the adoption of nursing models which, it is claimed, unifies nurses in distinctive approaches to caring. In Newfoundland, the current financial constraints in health care have created an opportunity to investigate the soundness of jumping on the nursing model "bandwagon". The author explores the meaning of nursing knowledge, the importance of developing knowledge for safe, effective practice, and explains how nursing models have become associated with nursing knowledge and imbued with almost mystical qualities. One aspect not seen in the literature-that of the cost of implementing a model for nursing care in hospitals-is presented. The implications, financial and ethical, are discussed and, in conclusion, another approach to encourage philosophizing about nursing work is outlined. PMID- 7888400 TI - Assessing the fears of children with disability using the Revised Fear Survey Schedule for Children: a comparative study. AB - This study compared the self-reported fears of children with disability using the Fear Survey Schedule for Children-Revised (FSSC-R). Children with intellectual disability reported a significantly greater number of fears than children with no disability, children with hearing impairment and children with visual impairment. Also the children with intellectual disability reported more idiosyncratic fears related to the unknown, injury and small animals. Consistent with normative findings (King et al., 1989b; Ollendick, King & Frary, 1989), girls reported significantly more fears than boys. Methodological issues are discussed including the reliability and validity of self-reported fears for children with disability. PMID- 7888403 TI - The implementation of theory-based nursing practice: laying the groundwork for total quality management within a nursing department. AB - Total Quality Management (TQM) is a management philosophy that has had great success in increasing quality and productivity in the private sector. Health care executives are interested in adapting this approach to a health care environment. This article discusses the implementation of theory based nursing practice as one initiative that lays the groundwork for the successful utilization of TQM in a nursing department. The barriers to quality are usually processes not people. Implementation of Jean Watson's nursing theory emphasizes that nurses are co participants in the processes of health care which results in better outcomes. Nurses are viewed as knowledge workers. Treating them as such, removes barriers to pride of workmanship and renews their commitment to the pursuit of excellence in their care. PMID- 7888404 TI - Outcome based management. AB - This article describes a conceptual framework for implementation of outcomes driven management. The framework is defined in terms of strategic and financial planning, and quality management. The concept of value for investment is explored and definitions are presented in the introduction. Background information provides an overview of the literature with an emphasis on management challenges and quality management. The methodology is described including implementation and evaluation. Experiential examples of implementation techniques and global outcomes in the three domains of service, service provider and service manager are presented. The article is concluded with advantages, disadvantages and summative remarks. PMID- 7888405 TI - Introducing quality management in the community: the VON experience. AB - How does a national, non-profit, community health organization introduce and implement quality management (QM) throughout its branches? This article traces VON's move from a traditional quality assurance model to a systematic QM approach, focused on customers and on outcomes. Implementing Quality Management in a three-tiered organization (national, provincial and local levels), with boards and staff, is not an easy challenge but is feasible. Effective and creative strategic planning is a necessity. Educational strategies and ideas for implementation are included. PMID- 7888406 TI - Walking the talk: one hospital's experience in implementing a conceptual framework for nursing practice. AB - There has been considerable impetus to use conceptual frameworks to guide nursing practice, yet many nursing theories are not supported by research or understood by nurses. At Foothills Hospital, a Committee developed and implemented a conceptual framework based on self-care. Concepts within the framework are grounded in current nursing practice, consistent with consumer expectations and supported by philosophical statements about patient, society/environment, health and nursing. PMID- 7888407 TI - Marketing strategies nurses can employ to promote health. AB - Marketing strategies are employed to ensure the success of new products, services or programs. Both profit and non-profit organizations have used social marketing strategies to inform, to motivate interest, and to engage the involvement of the consumer. A client-dependent health care system did not find it necessary to market services, but a health care system that encourages clients to choose the most appropriate health promotion service available must market services. Nurses are in the business of promoting the health of clients. Therefore, it is essential that nurses become familiar with, and involved in, the development of marketing plans and strategies. The connection between the four variables of the marketing mix (product, promotion, place, and price) and promoting the health of clients is described. A case example recapitulating the marketing strategies employed to raise public awareness of a self-help group for family caregivers is related, the marketing response is evaluated, and future recommendations are proposed. PMID- 7888408 TI - Caring: the raison d'etre of the professional nurse. AB - There is a belief in society that nursing is a profession and therefore that nurses are professional. There is also a belief that nurses care, that is, they care for their patients and consequently are a caring profession. However, we see and hear instances in which nurses do not act in a caring manner. Where this is the case, can they still be considered individually a professional, and collectively a profession? Is there a connection between caring and profession? Can a nurse be one without the other? The assertion of this paper, is that to be a professional nurse, a nurse must care. "Caring" and "profession" are defined and the components for a model of a professional relationship proposed. Nurses are challenged to find ways in which to reclaim their professional status by recapturing their commitment to caring. PMID- 7888409 TI - Evaluating the psychosocial component of nursing care in a geriatric program. AB - Today, most health care programs must operate within a framework of: 1) competing demands for resources, 2) pressure to reduce staffing levels, and 3) consumer demands for high quality service. Competing demands for resources means that there is a need to continuously justify a program by providing critical evaluations of program components and identifying effective outcome measures. Within a geriatric psychiatry program that provides assessment and short term treatment, various evaluation measures were tried. While none of the measurement techniques was completely satisfactory, it became very apparent that the psychosocial nursing skills that were critical in the care of this population were not accounted for by any of the current tools. Given the need to justify the high ratio of RN staffing to other categories, eg. CCA or LPN, two measures specific to nursing were tried on a pilot basis. This paper reports on the initial measurement techniques used and the results from the trial of new measures. PMID- 7888410 TI - The Delphi methodology (Part Two): A useful administrative approach. AB - The Delphi methodology can provide nurse administrators with relevant and accurate information to facilitate decision making. This paper, the second of a two part series, familiarizes nurse administrators with the application of the Delphi methodology in needs assessments, priority setting, changes in nursing practice, identification of cost containment approaches, development of effectiveness indicators, values clarification, and forecasting. Examples from the health sciences literature and our experiences in administration are presented to outline appropriate approaches for nurse administrators planning similar applications. PMID- 7888411 TI - Verbal and physical abuse of nurses. AB - In order to determine the extent to which nurses working in hospitals in the Toronto area experienced abuse, questionnaires were distributed to 2344 nurses working in either a large teaching hospital, a psychiatric hospital or a community hospital. Of the 603 nurses responding to the questionnaire, 199 (33%) had experienced abuse in their last five days at work. There were no statistical differences between the three hospitals in the incidence of abuse. The abuse was mainly verbal, from the patient and during the day shift. Although abuse occurred in all areas of the hospitals and was directed towards nurses with all levels of education, it was most frequently found in extended care and emergency areas and most often directed towards registered nursing assistants (RNAs). Administrators may be unaware of the high incidence of abuse since only 41% of the nurses reported the abuse to their immediate supervisors. PMID- 7888412 TI - Job sharing of a director of nursing position: an evaluation report. AB - The authors report on a job-share experience of Director of Nursing position at a large teaching hospital. A number of methods are used to evaluate this interim four month experience. Using aspects of administrative theory and the results of this evaluation, a conceptual framework is provided and suggestions are made that they may assist nurse and non-nurse administrators when considering future middle management job sharing arrangements in their organizations. PMID- 7888413 TI - The history and concept of recurrent brief depression. PMID- 7888414 TI - Prevalence of recurrent brief depression in primary care. AB - Descriptions of mentally ill inpatients have strongly influenced current classifications of mental disorders. Primary care patients may therefore present a substantially different pathology. Some diagnoses, infrequent in psychiatric settings but common in the general population or in primary care, have been described, such as the concept of recurrent brief depression (RBD) proposed by Jules Angst. RBD refers to frequent but short-lasting (usually only a few days) severe depressive episodes. In parallel with a study organized by the World Health Organization aimed at defining the psychological disorders encountered in primary care, we investigated the prevalence of RBD, its severity, and comorbidity with major and well-defined disorders using a structured interview (CIDI). The current prevalence of RBD in a general practice population was found to be about 10%. The average duration of the episodes is 3-4 days. Ours results confirm the severity of this disorder; in particular, a history of suicide attempts is frequent (23.3%). Among RBD patients, 26% do not present any other psychiatric disorder. When a comorbidity is reported, depressive episodes (lasting at least two weeks, according to ICD-10) and generalized anxiety disorder are the main associated disorders. Our results are in favor of the existence of RBD as a separate and original nosological entity. PMID- 7888415 TI - The relevance of recurrent brief depression in primary care. A report from the WHO project on Psychological Problems in General Health Care conducted in 14 countries. AB - This report from the WHO project on Psychological Problems in General Health Care examines the relevance in primary care of the concept of recurrent brief depression (RBD) proposed by Jules Angst. RBD refers to brief, severe depressive episodes that recur frequently, i.e. nearly once a month over a 1-year period, according to Angst. Using a structured interview (CIDI), RBD was assessed in patients not meeting the criteria for depressive episodes lasting at least 2 weeks, as defined in the ICD-10 (DE). A substantial proportion of primary care seekers were identified as presenting RBD without other depressive disorders, 3.7% with a formal RBD diagnosis and 2.7% with frequent but not monthly depressive episodes. These two subgroups were found to differ very little in terms of sociodemographic characteristics, severity, disability, and comorbidity with other diagnoses. However, in patients with a formal diagnosis of RBD, a higher rate of history of suicide attempts was found (14.0%), similar to that observed in patients meeting the criteria for DE. Most of the severity and disability indicators show that RBD is a severe condition, associated with substantial impairment, even if they show a higher degree of severity for DE. About one RBD patient out of three is recognized by general practitioners as presenting a psychological disorder, a majority of whom are actually treated. Our results confirm the relevance of the concept of RBD in primary care, and the need to further explore the pertinence of the restrictive recurrence criterion proposed by Angst. PMID- 7888416 TI - Brief depression among patients in general practice. Prevalence and variation by recurrence and severity. AB - Depression with substantial psychosocial impairment, but not qualifying as depressive disorder according to the standard diagnostic manuals, is frequent among primary care patients. Recurrent brief depression (RBD) is a diagnostic category intended to identify a major proportion of this group of patients. The WHO study on "Psychological Problems in Primary Health Care" was used as a vehicle to estimate the proportion of patients with this diagnosis and to evaluate the validity of this diagnosis as well as of alternative concepts of brief depression with multiple episodes. This study applies a two-stage sampling scheme; 300 patients also underwent an additional interview tailored for variants of brief depression. 7.6% of primary care patients were identified as RBD with the majority not receiving any other psychiatric diagnosis (DSM-III-R). These patients reported substantial psychosocial impairment, and the majority were identified as psychological cases by general practitioners. However, patients experiencing other variants of brief episodes were also found to be substantially psychosocially impaired, although they were not identified as psychiatric cases by DSM-III-R. Thus, a less restrictive definition of RBD is proposed. The diagnostic definition of RBD has a major impact on the sex ratio of cases: the less restrictive the diagnosis, the more balanced are the prevalence rates between males and females. PMID- 7888418 TI - Evidence for a seasonal form of recurrent brief depression (RBD-seasonal). AB - We have established a relationship between recurrent brief depression (RBD) and seasonal affective disorder (SAD) in a cohort of 42 outpatients who presented themselves at a clinic for seasonal affective disorder at the Psychiatry Department of the University of Bonn, Germany. Our preliminary data indicate that 31% of the patients who were diagnosed as suffering from either SAD or its subsyndromal form (S-SAD) can also be categorized as RBD (RBD-seasonal) for a 1 year observation period. During the time span of 1 year, RBD-seasonal patients had a mean number of 20 +/- 9 episodes, which were accentuated in fall/winter, outnumbering the ones in spring/summer significantly (P < 0.001). The mean duration of each episode was 4.6 +/- 2.6 days in the RBD-seasonal group. RBD seasonal patients experienced seasonal changes as more of a problem and reported a lower percentage of first-degree relatives with a history of depression than the non-RBD-seasonal group. PMID- 7888417 TI - Recurrent brief depression in general practice. Clinical features, comorbidity with other disorders, and need for treatment. AB - This study tested the clinical validity of the new diagnostic entity "recurrent brief depression" (RBD) in 300 general practice patients who participated in the WHO study on "Psychological Problems in Primary Care." Patients with current RBD reported of episodes major depression more often than did a comparison group of nondepressed general practice patients: however, the majority of RBD patients had not received a diagnostic of any well-established affective disorder during the last 12 months. RBD patients (without MDE) did not suffer more frequently from dysthymia, from nonaffective psychiatric disorders, or from somatic disorders. However, RBD was associated with a higher percentage of previous suicide attempts and of ideation of suicide and death. RBD was accompanied by substantial psychosocial impairment; psychosocial impairment in RBD patients could not be explained by excess comorbidity. Thus, the clinical validity of RBD was demonstrated although doubts about the appropriateness of the definition remained. This new diagnostic category needs more attention as only as small minority of patients with RBD received specific antidepressant treatment. PMID- 7888419 TI - Lack of efficacy of fluoxetine in recurrent brief depression and suicidal attempts. AB - Recurrent brief depression (RBD) fulfills DSM-III-R symptom criteria for major depression but the episodes are of shorter duration than the 2 weeks required by DSM-III-R. The clinical importance of the disorder has been observed in prophylactic studies of suicidal behavior. The possibility that antidepressants with selective action on the reuptake of serotonin might be effective in preventing recurrences of brief depression has been investigated. Fluoxetine in a dose of 120 mg a week, administered biweekly, had no effect on the recurrence rate, which was maintained at approximately the same rate on fluoxetine (1 every 18.7 days) as with placebo (1 every 17.6 days). In a group of patients with two or more prior episodes of suicidal behavior, there were 18 attempted suicides in the 54 patients treated with fluoxetine and the same number in the 53 patients treated with placebo. Fluoxetine neither raised nor lowered the suicide attempt rate as compared with placebo, providing no evidence to support the drug's role in either suicide provocation or prevention. Since fluoxetine is clearly effective with recurrent major depression, it would appear that recurrent brief depression has a different pharmacology. PMID- 7888421 TI - Distraction resulting from disease related words in alcohol-dependent inpatients: a controlled dichotic listening study. AB - To test whether alcoholics develop an information processing bias towards disease related stimuli, 30 alcoholic inpatients and 30 controls were administered a dichotic listening task. Three different stimulus types were presented to the right (ignored) channel: neutral words, rare neutral words and alcohol-related words. The hypothesized information processing bias should cause patients to make disproportionally more shadowing errors in the third condition. An ANOVA revealed a significant condition effect (P < 0.001), a tendency towards a group effect (P = 0.09) and a significant interaction (P < 0.01) in the expected direction. There was a marked increase of errors in alcoholics when disease-related stimuli were presented compared to the neutral conditions and to the controls. PMID- 7888422 TI - [Diagnostic value and therapeutic consequences of computerized tomography (patient outcome research)--1: Diagnosis in traumatology]. AB - During three months of 1993, 201 primary traumatologic patients (125 m, 76 f, x = 42.6 years) underwent 230 computed tomography examinations (= one CT of one body region) in the radiologic department of the Rudolf Virchow University Hospital. 87.0% of the CT's were performed completely without contrast media, 2.6% exclusively supported by intravenously given contrast media, 9.1% in both ways, and 1.3% after intra-articular contrast media administration. 97.4% served for primary diagnostic purposes and 2.6% for the control of therapeutic results. In 47.8% of the CT's, the principle diagnosis in the scanned body region was known before CT, i.e. by conventional X-ray examinations, but further detailed information was necessary to clarify the indication for operation and to choose the operative mode. In 52.2%, the diagnosis without CT was impossible by other, non-invasive and not more expensive methods. The CT diagnoses were correctly positive in 58.7% (suspected diagnosis verified, additional detail information...) and correctly negative in 41.3% (suspected diagnosis excluded). 60.9% of CT's demonstrated a missing indication for operation in the examined body region; in 39.1% the operation followed. The most frequently performed diagnostic methods before CT were conventional X-ray and sonography, whereas after CT further examinations were seldom needed. We conclude that traumatologic CT's contribute decisively to the reduction of costs by avoiding more expensive examination methods, avoiding redundant operations, and abridging stay duration in the hospital because of more efficient therapy planning. PMID- 7888420 TI - CSF levels of diazepam-binding inhibitor correlate with REM latency in schizophrenia, a pilot study. AB - CSF diazepam-binding inhibitor-like immunoreactivity (DBI-LI) and polysomnography were studied in 28 drug-free male schizophrenic (DSM-III-R) patients. They underwent a three-night polysomnography evaluation and a lumbar puncture. CSF DBI LI correlated positively with REM latency, the REM latency/2d nonREM period ratio and stage-4% sleep, and negatively with stage-1% sleep. CSF DBI-LI did not correlate significantly with duration of sleep or sleep latency. CSF DBI-LI during haloperidol treatment did not correlate significantly with sleep EEG measures. The results of this first study of the relationship between endogenous DBI and sleep in humans suggest that physiological effects of DBI other than interactions with the BZD/GABAA receptor complex may explain its positive effects on sleep. However, the absence of similar sleep data in normal subjects precludes us from establishing a specific relationship between DBI and sleep in schizophrenia. PMID- 7888424 TI - [3-phase spiral CT--a new noninvasive procedure for the differentiation of multifocal liver lesions]. AB - Dynamic CT is an established method for the differentiation of focal liver lesions by monitoring the contrast enhancement. It is especially restricted in the assessment of small and multiple lesions due to respiratory organ movements. Spiral-CT allows the examination of large volumes in the breathhold technique. Spiral-CT with controlled i.v. contrast media administration can be used for the assessment of the entire liver in distinct phases of perfusion. We describe the use of this new technique in a patient with multifocal nodular hyperplasia (FNH), for whom assessment with dynamic CT was not suitable. The lesions were first located with a conventional contrast-enhanced CT-scan. The impossibility to assess all the lesions with dynamic CT led to the decision to perform a three phase spiral-CT with three sequential scans (native, arterial, and portal perfusion phase). The entire liver was scanned after power injector-controlled i.v. administration of contrast media with the following parameters: 1) arterial phase: 70 ml contrast media, 2 ml/s, start delay 18 s; 2) portal phase: 80 ml contrast media, 2 ml/s, start delay 60 s; slice 8 mm, table feed 8 mm, increment 4 mm; 24 s of breathhold data acquisition. PMID- 7888423 TI - [Digital image intensification radiography in endoscopic retrograde cholangiopancreatography]. AB - The standard in ERCP is the use of the conventional radiography system. Digital radiography system are very seldom used in ERCP, and then mostly by digital luminescence radiography. In this study we report our experience with digital image amplification radiography (DIAR) in ERCP. We examined 53 patients of clinical routine aged from 21 to 90 years. During the ERCP we used the X-ray statues and the real-time exposures. At the end of an examination the image post processing followed. Both conventional and digital image amplification radiography needed the same examination conditions. The special X-ray protection (special lead-shields) used at digital ERCP did not hinder the examination. The DIAR provided at least the same amount of information as conventional radiography. An advantage of DIAR is the possibility of image post-processing such as contrast change, zooming, etc., and the digital archiving and communication. The examination time was reduced by about 30% as compared conventional ERCP, resulting in a reduction of the X-ray exposure time for the patients. The disadvantages of DIAR can surely be compensated by a high ERCP rate. PMID- 7888425 TI - [Diagnostic imaging in primary hepatobiliary cystadenoma of the liver]. AB - The clinical and radiological findings of 5 patients with a total of 7 hepatobiliary cystadenomas are reported. In all cases sonography and computed tomography were performed, in three cases angiography was carried out, and in one case magnetic resonance imaging was used. On sonography and computed tomography hepatobiliary cystadenomas exhibit relatively typical findings as a multicystic, space-occupying lesion with septation and papillary mucosal nodes; hence the diagnosis can be made preoperatively in most cases. For differential diagnosis, the malignant form, hepatobiliary cystadenocarcinoma has to be considered which can only be distinguished from the benign form by histology. PMID- 7888426 TI - [Spiral CT of abdominal aortic aneurysm]. AB - Aneurysms of the aorta abdominalis necessitate a fast and easy diagnostic procedure before the patient is ready for vessel surgery. For the example of 15 cases, we demonstrate our good experience by using spiral-CT with intravenous contrast administration. We also present a short protocol to handle this examination. PMID- 7888427 TI - [Diagnostic possibilities of magnetic resonance tomography (MRT) and magnetic resonance angiography (MRA) in popliteal artery entrapment syndrome (PAES)]. AB - MRT offers some advantages for morphological examinations of the fossa poplitea and appears to be superior in terms of multiplanar imaging over CT and duplex sonography for identifying a PAES. The method is always indicated when the diagnosis of PAES is suspected from the primary duplex sonography but the verification of the anatomic alteration is not conclusive. An MR angiography can, in principle, be carried out in the same session. On consideration of the currently presented cases, both inflow and phase-contrast MRA appear to be suited for examination. However, a sufficient detail resolution is only achieved by use of a surface coil which then makes assessment of the contralateral side and the lower leg arteries impossible. Specially fitted coils which allow a double-sided representation of sufficient image quality may, however, make conventional angiography unnecessary in future. PMID- 7888428 TI - [Magnetic resonance tomography of finger polyarthritis: morphology and cartilage signals after ademetionine therapy]. AB - This report deals with a prospective study of 21 patients with finger osteoarthritis treated over a period of three months with either Ademetionin (therapy group: 14/21) or without (control group: 7/21). MR-Imaging was carried out before and after treatment using spin-echo and 3D-Flash sequences. Morphological parameters and signal intensity changes of the hyaline cartilage were evaluated. The increase of the cartilage signal intensity was significant in the therapy group, this can be interpreted as an structural improvement. Also a decrease of the cartilage signal intensity with age was found. The morphological parameters showed no significant changes in the therapy and control groups. PMID- 7888429 TI - [Diagnosis of fractures of the occipital condyles]. AB - The imaging diagnosis of occipital condyle fractures by CT and MRT is reported for cases of 4 patients. Following the conventional X-ray diagnosis of the skull and upper cervical spine, CT proved to be the primary diagnostic method after a skull and brain injury: for all 4 cases we succeeded in detecting the occipital condyle fracture and in determining its size and location by reconstructions (coronal, sagittal, 3-D). In the case of complex accompanying injuries like soft tissue hematomas (cerebral, in the spinal cord, and the soft tissue of the neck) or for the detection of brain stem contusion, MRT had significant advantages. MRT can offer a higher image quality in soft tissue, especially in the spinal cord and the brain. PMID- 7888430 TI - [Diagnosis of the site and extent of breast carcinoma]. AB - The value of X-ray-mammography, ultrasound, and MRI are compared with regard to their results in localization, differential diagnosis, and staging of carcinomas of the breast. For microcalcifications that are only imaged by mammography, X-ray is superior to the other imaging modalities and remains method of choice. Ultrasound is the most useful to differentiate cystic and solid lesions. The value of MRI is not yet proved sufficiently except in conservative and plastic surgery of breast carcinoma. PMID- 7888431 TI - [Osseous manifestations of Bourneville-Pringle disease]. AB - Tuberous sclerosis (Bourneville-Osseous Manifestations of Bourneville-Pringle's Disease) is a rare disease characterised by the clinical traid of epilepsy, mental retardation and adenoma sebaceum. In addition of this triad a number of patients shows other visceral, neurocutaneus or osseous manifestations. We describe the radiological findings of two patients with typical skeletal changes. PMID- 7888433 TI - [High-resolution CT in the early and late form of lymphangioleiomyomatosis]. AB - We report on two cases of pulmonary lymphangiomyomatosis, one of which was diagnosed by chance. Retroperitoneal lymphomas were found during a routine "check up" and biopsy proved a lymphangiomyomatosis (LAM). High resolution CT of the lung was typical for pulmonary LAM. The other patient was examined because of a progressive dyspnea and hemoptysis. We compared the high-resolution CT of the early manifestation of LAM with that of a progressive disease. In both, the results of the high-resolution CT were pathognomonic. PMID- 7888432 TI - [Sapho syndrome: 2 case reports]. AB - We report on two patients with painful hyperostosis of the mandible and the thoracic skeleton. Other symptoms were arthralgia, arthritis, osteitis, and palmoplantar pustulosis. Radiographic analysis revealed regions of circumscribed hyperostosis which showed in increased uptake in scintiscan. Metastasis, chronic osteomyelitis, Ewing's sarcoma, or Paget's disease were excluded and the diagnosis Sapho syndrome was made. This recently introduced acronym describes a disease with Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis. Because of the possible axial skeleton involvement, an association to the spondylathropathy group is still being discussed. The etiopathogenesis of this rheumatologic disease is not known. PMID- 7888434 TI - [Computerized tomography image of pulmonary alveolar proteinosis]. AB - Pulmonary alveolar proteinosis is a rare disease of uncertain etiology. It progresses with alveolar deposits of PAS-positive material, exhibits in the long term interstitial changes of the lung skeleton, and can be complicated by superinfections. The computed tomographic image is characterized by geographically sharply delineated alveolar infiltrates, faint, ground-glass-like parenchymal turbidity, with well bordered interstitial structures and recesses in the subpleural space. PMID- 7888435 TI - [Non-granulomatous prostatitis: MRI image with endorectal surface coil ("Endo MRI")]. AB - Inflammatory conditions of the prostate are often difficult to distinguish from early stages of prostate cancer with imaging techniques. The use of an endorectal surface coil in MRI of the prostate gland has been reported to provide superior resolution and better imaging of details than MRI with a body coil in the diagnosis of early prostate cancer. We report a 34-year-old patient with nonspecific non-granulomatous prostatitis in whom T2-weighted endorectal surface coil magnetic resonance imaging (ESCMRI) showed a region of markedly decreased signal intensity in the periphery of the gland. The low signal intensity of the lesion, its sharp demarcation from the normal part of the peripheral zone of the prostate and the marked bulge of the surface contour without capsular breach of the organ were interpreted as evidence of a bioptically proven benign inflammatory condition. PMID- 7888436 TI - [Spiral CT of the thorax with double table feed in relation to slice thickness]. AB - PURPOSE: The aim of the study was to reduce investigation time, radiation dose, and contrast material when performing spiral-CT of the thorax. METHODS: 50 patients with different clinical diagnoses underwent spiral-CT of the thorax with double table feed and 45 ml contrast material (lopentol) were injected. Density measurements were performed as follows: main pulmonary artery without contrast injection, carotid artery, subclavian artery, ascending and descending aorta, aortic arch, main pulmonary artery and thoracic aorta after contrast injection. RESULTS: In comparison to the density of the main pulmonary artery without contrast injection there was an increase of density of 134 HU. 45 ml of the contrast agent were sufficient in all cases for delineation of the mediastinal vessels. Investigation time was 16-18 s and all patients were able to hold their breath during this time, so no artifacts were seen. Radiation dose was cut in half. CONCLUSION: Spiral-CT with double table feed enables investigations of the thorax in less than 20s. 45 ml of a contrast agent are sufficient for performing this examination. There are no essential diagnostic deficits with this technique. PMID- 7888437 TI - [Right aortic arch simulates mediastinal tumor: diagnosis with spiral CT]. AB - We report the case of a patient with right aortic arch (type III) mimicking a mediastinal tumor. We discuss the radiological findings together with their embryologic correlations, and emphasize the role of spiral-CT in the acquisition of imaging data under difficult diagnostic conditions. PMID- 7888438 TI - Prenatal screening for neural tube defects and chromosome abnormalities: the complexities of program evaluation. PMID- 7888439 TI - Paternal serum dioxin and reproductive outcomes among veterans of Operation Ranch Hand. AB - We studied whether paternal exposure to Agent Orange and its dioxin contaminant (2,3,7,8-tetrachlorodibenzo-p-dioxin) during the Vietnam War is related to adverse reproductive outcomes after service in Southeast Asia. The index cohort comprises conceptions and children of veterans of Operation Ranch Hand, the unit responsible for aerial spraying of herbicides in Vietnam from 1962 to 1971. The comparison cohort comprises conceptions and children of Air Force veterans who served in Southeast Asia during the same period but who were not involved with spraying herbicides. We found no meaningful elevation in risk for spontaneous abortion or stillbirth. In analyses of birth defects, we found elevations in risk in some organ system categories, which, after review of the clinical descriptions, were found to be not biologically meaningful. There was an increase in nervous system defects in Ranch Hand children with increased paternal dioxin, but it was based on sparse data. We found no indication of increased birth defect severity, delays in development, or hyperkinetic syndrome with paternal dioxin. These data provide little or no support for the theory that paternal exposure to Agent Orange and its dioxin contaminant is associated with adverse reproductive outcomes. PMID- 7888440 TI - Agricultural work during pregnancy and selected structural malformations in Finland. AB - We studied the relation between birth defects and maternal agricultural work in a nationwide time- and area-matched case-referent series of 1,306 pairs of infants (581 orofacial clefts, 365 central nervous system defects, 360 skeletal defects) obtained through the Finnish Register of Congenital Malformations. We supplemented the Register data, including the mothers' latest and previous pregnancies, diseases, consumption of drugs and alcohol, smoking habits, and the like, with detailed interviews on the mothers' work conditions. When all of the birth defects were pooled and agricultural work was compared with nonagricultural work in the first trimester of pregnancy, the adjusted odds ratio was 1.4 [95% confidence interval (CI) = 0.9-2.0]. For orofacial clefts, the corresponding odds ratio was 1.9 (95% CI = 1.1-3.5). An industrial hygienist's blinded assessment indicated that seven mothers of infants with orofacial clefts and three reference mothers had been exposed to pesticides in agricultural work; the adjusted odds ratio for work with pesticide exposure, when compared with unexposed agricultural work, was 1.9 (95% CI = 0.4-8.3). Exposure to solvents did not explain the observed association. PMID- 7888441 TI - Childhood cancer occurrence in relation to power line configurations: a study of potential selection bias in case-control studies. AB - Several case-control studies have reported positive associations between childhood cancer and proximity to high-current residential power lines as defined by the Wertheimer-Leeper code. We conducted a study to evaluate whether or not differential nonparticipation of controls as a function of socioeconomic status is likely to account for the observed associations. We assessed the relation of annual family income to the Wertheimer-Leeper code in a sample of 392 households in western Washington state, and we evaluated the magnitude of bias that could occur from differential participation of low- and high-income eligible controls. Very-high-current configurations were most frequently located among households with self-reported family income of less than +15,000 per year, and very-low current configurations were most frequently located among those with self reported family income of more than +45,000 per year. In a hypothetical case control study in which: (1) it was assumed that there is no true etiologic relation between power line configurations and cancer occurrence, and (2) controls with very low income were less likely to participate than others, observed (biased) odds ratios ranged from 1.03 to 1.24. If these results are applicable to other areas where case-control studies of cancer in relation to power lines have been conducted, they suggest that relatively lower participation among exposed controls (as a function of very low income) is not likely to account for the elevated risks of 1.5- to 3-fold that have been observed in these previous studies. PMID- 7888442 TI - Prospective cohort study of risk factors for primary liver cancer in Hiroshima and Nagasaki, Japan. AB - We investigated risk factors for primary liver cancer among a cohort of 36,133 residents in Hiroshima and Nagasaki, Japan, originally established to examine the association between exposure to atomic bomb radiation and disease. A mail survey to study the late effects of atomic bomb radiation was conducted among the cohort between 1978 and 1981. During the subsequent follow-up period (average 8.61 years), 242 cases of primary liver cancer were identified through population based tumor registries in the two cities. The relative risk (RR) of liver cancer was 2.23 [95% confidence interval (CI) = 1.53-3.23] for tobacco smokers compared with those who had never smoked. Alcohol use was slightly positively associated with the risk of liver cancer, and men who had quit drinking had an RR of 2.33 (95% CI = 1.34-4.07) compared with those who never drank. Among alcohol drinkers, an inverse relation between years of abstinence and the rate of liver cancer was found, possibly attributable to a confounding effect of preclinical disease. The use of female hormone preparations was modestly associated with the risk of liver cancer (RR = 1.29; 95% CI = 0.59-2.84). Other risk factors included a self reported history of radiation therapy (RR = 1.79; 95% CI = 1.31-2.43). PMID- 7888443 TI - Paternal TCDD exposure and pregnancy outcome. PMID- 7888444 TI - Use and limitations of the capture-recapture method in disease monitoring with two dependent sources. AB - Capture-recapture techniques are employed increasingly to correct for underascertainment of cases in epidemiologic surveillance. A key assumption of the basic two-source capture-recapture method is the independence of sources, which is often violated in practice. This paper provides a quantitative comparison of the performance of the capture-recapture method and the traditional registration approach in disease monitoring with two dependent sources. If sources are negatively dependent, underascertainment of cases by the traditional registration approach is transformed into overestimation of case numbers with the capture-recapture method. This overestimation can be extreme under certain conditions. Application of the capture-recapture method is therefore discouraged if negative source dependence is of concern. In other situations, the capture recapture method can be a valuable tool to correct for underascertainment of cases. Although the correction remains imperfect if notifications from both sources are positively dependent, underestimation of case numbers is typically much less severe than with the traditional registration approach. I illustrate the findings for a broad range of registration scenarios and provide empirical examples from population-based cancer registration. I also discuss strategies that may minimize the degree of source dependence in the design and analysis of capture-recapture studies. PMID- 7888445 TI - Gastroduodenal toxicity of different nonsteroidal antiinflammatory drugs. AB - Although the etiologic relation between nonsteroidal antiinflammatory drug (NSAID) use and gastrointestinal lesions is well documented, newly introduced NSAIDs deserve a fresh examination for their risk/benefit ratio. To estimate the association between consumption of ketorolac and the occurrence of gastroduodenal lesions, we conducted a case-control study. The study population comprised 600 outpatients with a confirmed endoscopic diagnosis of ulcer and erosion in 1991 and 1992 and 6,000 community controls matched by age and sex. We retrieved the prescription history through a computerized prescription monitoring system. We defined exposure to each study drug as "current" (month of endoscopy and preceding month), "recent" (second or third month preceding endoscopy). and "past" (fourth to sixth month preceding endoscopy). Current users of NSAIDs showed a 30% increase in the incidence of gastroduodenal lesions [odds ratio (OR) = 1.3; 95% confidence interval (CI) = 0.98 - 1.8] after adjustment for recent or past use of any NSAID, recent or past gastrotoxic therapy, recent or past use of gastroprotective drugs, and recent or past use of any other drug. Among NSAIDs, ketorolac was the only one showing a distinctly elevated risk of gastroduodenal lesions (OR = 4.2; 95% CI = 1.9-9.4). Current use of any NSAID was associated with almost a doubling of risk for ulcer alone (OR = 1.9; 95% CI = 1.3-3.0); no elevation in risk was found for erosions. The adjusted relative risk for ulcer associated with current use of ketorolac was 9.8 (95% CI = 3.4-28.10. Recent and past use of NSAIDs does not increase the risk of ulcer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888446 TI - Estimating standardized mortality odds ratios with national mortality followback data. AB - Proportionate mortality analyses are often used to study cause-specific mortality when population denominators are not available. The purpose of this paper is to present an extension of published proportionate mortality ratio logistic regression methods used to analyze such data. This paper describes methods used to estimate standardized mortality odds ratios (SMORs) with numerator data and the problems encountered when external standard rates are not available for all strata of interest. This paper focuses on the case where one has representative mortality followback data. These data are based on a large, representative sample of deaths from a defined population for whom numerous covariates about the decedents are collected from surviving family members. With these data, one may use logistic regression methods to generate fully standardized estimates of risk, SMORs, with numerator data. It is also possible to generate SMORs that allow for effect modification. Mortality followback data are also a more flexible data source from which one may generate substitutes for external standard mortality rate ratios to be used with previously developed SMOR methods. An application of the methods is provided using logistic regression. PMID- 7888447 TI - Pesticides and birth defects. PMID- 7888448 TI - The validity of self-reports of past body weights by U.S. adults. AB - Past weight or patterns of weight change may be more important to chronic disease risk than current weight. Self-reports, however, are often the only source of information about past body weight. To date, very few studies have examined factors affecting the validity of self-reported past body weight. We examined the validity of self-reported past body weights of 1,931 U.S. adults who were participants in the First National Health and Nutrition Examination Survey (1971 1975) and were interviewed again in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (1982-1984). We compared the body weight measured during the initial examination (1971-1975) with the recalled 1971-1975 body weight reported during the follow-up interview (1982-1984). Recalled past weight was strongly correlated with previously measured weight (r = 0.73 for men, and r = 0.74 for women). Men overestimated their past body weight, whereas women underestimated their past weight. Although 39% of men and 41% of women estimated their past weight within 5 pounds, approximately 17% of women and 10% of men underestimated their past weight more than 15 pounds. Accuracy of reporting was influenced by sex, race, current body mass index, and the amount of weight gained over the 10 years following the initial examination. These factors should be considered when using recalled weight in epidemiologic studies. PMID- 7888449 TI - Validation of self-reported history of acute myocardial infarction: experience of the Minnesota Heart Survey Registry. AB - Accurate separation of new cases of acute myocardial infarction from prevalent cases is critical for assessing trends in morbidity in population-based studies. This report presents data on the validity of self-reported history of previous acute myocardial infarction among 3,703 patients admitted to a coronary care unit with suspicion of acute myocardial infarction. We substantiated the history of a prior event for 60% of those who reported one (629 of 1,053) and found 40% to be false-positive histories. Much of the false-positive reporting was related to previous cardiac hospitalizations, predominantly (40%) for unstable angina. PMID- 7888450 TI - Low blood pressure and mortality in the elderly: a 6-year follow-up of 18,022 Norwegian men and women age 65 years and older. AB - Several studies have shown that low blood pressure in individuals age 65 years and older is related to increased overall mortality. We hypothesize that this association is secondary to serious underlying illness, which has caused blood pressure reduction and, subsequently, has increased the risk of dying. Our study population was comprised of individuals age 20 years and older in the county of Nord Trondelag in Norway, who were studied in a general health survey between 1984 and 1986. We had measurements of blood pressure, blood glucose, weight, height, and other information for 9,732 women and 8,290 men age 65 years or older. During approximately 6 years of follow-up, 2,122 women and 2,578 men died. For both genders, low systolic pressure was not associated with increased mortality, and the mortality curve did not display a J-shaped relation, after adjustment for age, marital status, body mass index, blood glucose, self-assessed health, use of antihypertensive medication, and history of diabetes and cardiovascular diseases. For diastolic pressure, however, women in the lowest category (< 75 mmHg) had an adjusted mortality rate ratio of 1.21 (95% confidence limits = 1.05, 1.39), compared with reference women (80-87 mmHg). Among men, the analogous mortality rate ratio was 1.16 (95% confidence limits = 1.02, 1.31). To reduce further the potential confounding between diastolic pressure and underlying illness, we excluded users of antihypertensive medication as well as the 2 first years of follow-up. After these procedures, the J-shaped mortality curve was not present among women, and it was substantially reduced among men. Thus, the results for both men and women indicated that the age-adjusted J-shaped relation between diastolic blood pressure and mortality was confounded with indicators of ill health, and that the often-found association between low diastolic blood pressure and increased mortality is indirect, possibly caused by serious underlying disease. PMID- 7888451 TI - Reproducibility and validity of an extensive semiquantitative food frequency questionnaire among Greek school teachers. AB - We evaluated the reproducibility and validity of a 190-item semiquantitative food frequency questionnaire (FFQ) to be used in a large prospective study in the Athens area of Greece. Eighty persons, 42 men and 38 women, ages 25-67 years, completed a self-administered FFQ, followed by monthly 24-hour diet recalls and then a second FFQ 1 year after the first. Correlation coefficients measuring the reproducibility and validity of the FFQ indicate that the questionnaire is reproducible and provides a reasonably reliable measure of intake for many nutrients over a period of 1 year. PMID- 7888452 TI - The moral bases for public health interventions. PMID- 7888453 TI - On adjusting for the outcome of previous pregnancies in epidemiologic reproductive studies. PMID- 7888454 TI - beta-Carotene supplementation, vitamin D, and cancer risk: a hypothesis. PMID- 7888455 TI - Limitations of nutritional data. PMID- 7888456 TI - Coronary artery disease and lipid fractions. PMID- 7888457 TI - Second thoughts on time-specific study base restriction. PMID- 7888458 TI - Predicting responses in humans using animal study results. PMID- 7888459 TI - Antihypertensive therapy and blood lipids. PMID- 7888460 TI - Sequential tests for cohort and case-control studies. PMID- 7888461 TI - Meriwether Lewis' cause of death. PMID- 7888463 TI - Shift in body mass index distributions due to height loss. PMID- 7888462 TI - Meriwether Lewis' cause of death. PMID- 7888464 TI - Computational realization of point and interval estimation for risk and rate advancement periods. PMID- 7888465 TI - Hypoxaemia in the general surgical ward--a potential risk factor? AB - After major operations, hypoxaemia is common in the late postoperative period in the surgical ward. Recent studies of humans after major operations showed that such hypoxaemia may be related to the development of myocardial ischaemia and cardiac arrhythmias, even in patients with no preoperative signs or symptoms of coronary artery disease. Experimental studies have shown 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 postoperative period. Hypoxaemia may therefore prove to be a risk factor in the late postoperative period, and further studies are needed to clarify its pathogenesis and rational treatment. PMID- 7888466 TI - Civilian low velocity gunshot wounds of the liver. AB - OBJECTIVE: To report our experience in the management of hepatic gunshot wounds. DESIGN: Retrospective study of medical records. SETTING: University department of surgery, Finland. SUBJECTS: 38 patients admitted with hepatic gunshot wounds confirmed at operation. INTERVENTIONS: Laparotomy in all cases. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: Of the 35 low velocity bullet wounds of the liver, 23 (66%) were severe, but 34 (97%) could be managed with simple operative techniques. Two of the three shotgun injuries were at point-blank range, and one required lobectomy. Four patients (11%) died, and in all cases haemorrhage from associated cardiovascular injuries was a major contributing factor. Postoperative morbidity after bullet wounds was 57%, including two local hepatic complications. CONCLUSIONS: Simple operative repairs are sufficient and safe in most patients with low velocity bullet wounds of the liver. Associated injuries are the main cause of postoperative mortality and morbidity. Point-blank shotgun injuries involving the liver are not necessarily fatal. PMID- 7888467 TI - Treatment of blunt injury of the spleen: is there a place for mesh wrapping? AB - OBJECTIVE: To describe our experience of treatment of blunt injury to the spleen and to assess the contribution of observation and mesh wrapping to outcome. DESIGN: Retrospective study. SETTING: Teaching hospital, Norway. SUBJECTS: 50 consecutive patients with blunt injuries to the spleen treated between 1987 and 1992. INTERVENTIONS: 36 of the 50 were operated on (15 of whom had other injuries as well). 19 Underwent splenectomy and the others had various conservation measures including 8 who had absorbable mesh wrapping applied. RESULTS: 14 Patients were successfully treated by observation alone (mean 8 days, range 4 14). 24 were operated on within 3 hours, and 12 after a period of observation, by a total of 18 surgeons (9 of whom dealt with only one such injury each). Half the eight patients who had absorbable mesh applied developed complications (rebleeding and pleural effusion, n = 2 each). Two patients died: one was a baby with an associated severe head injury and one had cirrhosis of the liver and had initially refused treatment but was admitted in a critical condition and died of coagulopathy after splenectomy. CONCLUSION: Conservation with absorbable mesh wrapping should be attempted more often, but experience is necessary to do it properly. Given a protocol with explicit criteria for operation, we suggest that haemodynamically stable patients who require little or no blood transfusion should be observed carefully in the first instance. PMID- 7888468 TI - Appraisal of the use of an externally supported polytetrafluoroethylene graft in left gastric vein to inferior vena cava shunting. AB - OBJECTIVE: To assess the results of left gastric vein to inferior vena cava (IVC) shunts with externally supported (ringed) polytetrafluoroethylene (PTFE) grafts in six patients with considerably dilated left gastric veins who required portal decompression. DESIGN: Open study. SETTING: University hospital, Japan. SUBJECTS: Six patients with advanced portal hypertension and massive oesophageal bleeding. INTERVENTIONS: The PTFE graft was first anastomosed end to side to the IVC, and then end to end (n = 4) or end to side (n = 2) to the left gastric vein. MAIN OUTCOME MEASURES: Short term and long term morbidity and mortality. RESULTS: There were no operative mortality or morbidity. Endoscopic examination postoperatively showed gradual, steady improvement in the oesophageal varices, and the hyperaemic appearance of the mucosa had disappeared within 10 months in all cases. Median follow up was 19 months (range 10-70); one patients rebled after occlusion of the graft at 12 months, one died of hepatocellular carcinoma at 16 months, and the remaining four patients are well with patent grafts at 10, 22, 40, and 70 months, respectively. CONCLUSIONS: These results confirm the effectiveness of externally supported PTFE grafts in left gastric vein to IVC shunts, and remove the technical restraints that have prevented surgeons from recommending the operation in the past. PMID- 7888469 TI - Gastric leiomyosarcoma: a clinicopathological review. AB - OBJECTIVE: To report our experience of eight patients with primary gastric leiomyosarcoma. DESIGN: Retrospective study. SETTING: Teaching hospital, Taiwan. SUBJECTS: 8 patients who presented with primary gastric leiomyosarcoma between 1986 and 1990. MAIN OUTCOME MEASURES: Endoscopic, radiological, and histopathological features, DNA ploidy, and outcome. RESULTS: Abdominal pain and gastrointestinal bleeding were the most common presenting symptoms. In 5 of the 7 patients who had endoscopy preoperatively a diagnosis of submucosal tumour was made, but a definite diagnosis of leiomyosarcoma was made in only 3. A provisional diagnosis of leiomyosarcoma was made in 3 of the 4 patients who had computed tomography. All patients underwent some form of gastric resection ranging from palliative resection to total gastrectomy. Patients in whom the tumour had invaded adjacent organs had a poor prognosis. Histopathological grading of tumours correlated well with DNA ploidy. CONCLUSION: Both histopathological grading and DNA ploidy could be helpful objective prognostic criteria in patients with primary gastric leiomyosarcoma. PMID- 7888470 TI - Clinical and endoscopic signs for the prediction of recurrent bleeding from gastroduodenal ulcers. AB - OBJECTIVE: To evaluate the prognostic importance of various clinical and endoscopic signs in patients who rebled after endoscopic treatment of gastroduodenal ulcers, and to create a predictive index using regression analysis. DESIGN: Retrospective study. SETTING: Teaching hospital, Lithuania. SUBJECTS: 659 patients whose bleeding peptic ulcers were treated endoscopically (out of a total of 949 with bleeding peptic ulcers seen from 1982-1991). INTERVENTIONS: Endoscopic haemostasis (laser or electrocoagulation, or injection sclerotherapy). MAIN OUTCOME MEASURES: Mortality, incidence of rebleeding, and identification of prognostic factors. RESULTS: Of the 75 patients who rebled 25 died (33%), compared with 23 of the 584 who did not (4%). 57 patients (76%) rebled within two days of endoscopy, and 70 (94%) within a week. 59 variables from the group of 75 who rebled and from a control group of 100 who did not were analysed by logistic regression to construct a predictive index. The following 12 variables were found to be significantly associated with recurrent haemorrhage: frequency and type of bleeding; length of time between episodes of bleeding at home; shock index on admission; speed of reduction in haemoglobin concentration; size and type of ulcer, and whether it was complicated; endoscopic appearance of ulcer; number of ulcers, sex of the patient, and presence of associated diseases (liver disease, coagulopathy, hypertension, or heart disease). The accuracy of the index varied from 78.4% in the prediction of a high risk of rebleeding to 100% in the prediction of a low risk. CONCLUSION: By using the predictive index we have been able to improve our management of patients with bleeding peptic ulcers. PMID- 7888471 TI - Effect of xylene clearance of mesenteric fat on harvest of lymph nodes after colonic resection. AB - OBJECTIVE: To find out if clearance of surgical colectomy specimens with xylene gave a higher yield of lymph nodes and more accurate staging than the traditional step-sectioning technique. DESIGN: Consecutive open study. SETTING: Private hospital, United States. MATERIAL: 84 specimens from colonic resections, 4 of which were total colectomies and the remaining 80 segmental resections. INTERVENTIONS: The first 41 (2 colectomies and 39 segmental resections) were cleared by step-sectioning alone (to establish baseline values). The remainder (n = 2 and 41, respectively) were step-sectioned, the lymph nodes were removed, and then the residual tissue was cleared with xylene. MAIN OUTCOME MEASURES: The number of lymph nodes found, and if the diagnosis was changed by the finding of additional nodes. RESULTS: The baseline values in the two total colectomy specimens were 76 and 101, and the mean (range) after segmental colectomy was 21 (1-98). The values after total colectomy in the second group were 33 and 73, and after xylene clearance an additional 12 and 17 nodes were found. After segmental colectomy a mean (range) of 13 (0-43) was found, and an additional 4 (0-12) were found after xylene clearance. No additional nodes containing metastases were found in total colectomy specimens after xylene clearance, and only 6 additional nodes after segmental resection contained metastases. These changed the histological stage of the disease in only 2 patients. CONCLUSIONS: Xylene clearance offers little advantage over careful traditional step-sectioning of specimens, but may be of value if the histopathologist does not do routine meticulous step-sectioning. PMID- 7888472 TI - Fatal outcome of spontaneous rupture of the stomach in a patient with anorexia nervosa. PMID- 7888473 TI - Ectopic fallopian tube and ovarian cystadenocarcinoma in an inguinal hernia. PMID- 7888474 TI - Rightsided segmental infarction of the omentum. PMID- 7888475 TI - Colonic stricture secondary to haemolytic uraemic syndrome. PMID- 7888476 TI - Parallel determination of gut permeability in man with M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol. AB - Polyethylene glycol has been in use for a number of years for the assessment of gut permeability. The methods so far employed are usually limited to polyethylene glycols in the low relative molecular mass range (up to M(r) 1300). We developed a method for the simultaneous determination of gut permeability to M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol, by applying a single oral dose of an appropriate mixture of these polyethylene glycols. After extraction from 24 h-urine, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol were quantified by size exclusion chromatography, while M(r) 400 polyethylene glycol was determined by reversed phase chromatography. The detection limit of polyethylene glycol in the relative molecular mass range between M(r) 1500 and M(r) 10,000 was found to be 0.2 mg/l urine, and the detection limit of M(r) 400 polyethylene glycol 5 mg/l urine. Recovery of the polyethylene glycols (N = 6) were 86.6% (CV: 4.8%) for M(r) 400, 94.1% (CV: 7.2%) for M(r) 1500, 97.1% (CV: 5.5%) for M(r) 4000 and 97.4% (CV: 5.6%) for M(r) 10,000. No significant difference was found between the excretion rates in 24 h-urine of M(r) 400 and M(r) 1500 polyethylene glycols in patients with Crohn's disease (M(r) 400: 34.4 +/- 5.5%; M(r) 1500: 5.22 +/- 2.27%; mean +/- SEM, N = 10) and healthy controls (M(r) 400: 33.6 +/- 3.2%, M(r) 1500: 1.09 +/- 0.26%; N = 21). The excretion rate of M(r) 4000 polyethylene glycol was markedly higher in patients with Crohn's disease (0.462 +/- 0.177%) than in healthy controls (0.049 +/- 0.012%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888477 TI - Oxalic acid in saliva, teeth and tooth tartar. AB - Oxalic acid was determined in human saliva, teeth, tartar, and in animal teeth. Saliva from dentally healthy male subjects contained 0.10 +/- 0.09 mmol/l (n = 41) and those of dentally healthy female subjects 0.18 +/- 0.17 mmol/l (n = 40). Oxalic acid in tartar from 16 patients was 3.3 +/- 1.2 mmol/kg tartar. In human teeth, oxalic acid was 1.0 +/- 0.3 mmol/kg in milk teeth (n = 12) and 0.9 +/- 0.6 mmol/kg in permanent teeth (n = 60). Human teeth were sorted into age groups and into molars, incisors and premolars. In animal teeth, oxalic acid content varied widely. The formed calcium oxalate is proposed to be a 'physiological' protective mechanism for teeth. PMID- 7888478 TI - Accelerated bone degradation in thyroid carcinoma patients during thyroxine treatment, measured by determination of the carboxyterminal telopeptide region of type I collagen in serum. AB - We studied the effects of long-term suppressive thyroxine treatment on serum markers of bone collagen synthesis and degradation in thyroid carcinoma patients, and the relationship of these effects to the serum concentrations of thyrotropin, free thyroxine and free triiodothyronine were investigated. Thirty-seven thyroid carcinoma patients receiving a stable thyroxine dose, and thirty-five controls participated in a cross-sectional study. Bone collagen synthesis and degradation were measured by using specific radioimmunoassays to determine the serum concentrations of carboxyterminal propeptide of type I procollagen, and carboxyterminal telopeptide region of type I collagen, respectively. Serum thyrotropin, free T4 and free T3 were measured by time-resolved fluoroimmunoassays (Delfia). Serum carboxyterminal telopeptide region of type I collagen concentrations of thyroid carcinoma patients were significantly higher than those of the controls (p = 0.0012). Serum carboxyterminal propeptide of type I procollagen concentrations did not differ significantly between the patients and controls (p = 0.85). Significant associations between age or physical activity, and carboxyterminal propeptide of type I procollagen or carboxyterminal telopeptide region of type I collagen were found in the controls, but not in the patients. Thyrotropin, free T4 or free T3 were not significantly associated with carboxyterminal propeptide of type I procollagen or carboxyterminal telopeptide region of type I collagen in either the control or patient group. From these results it is concluded that long-term suppressive thyroxine treatment seems to accelerate bone degradation, but not bone formation, and therefore carries a risk for osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888479 TI - Increased Na+/Mg2+ antiport in erythrocytes of patients with cystic fibrosis. AB - Na+/Mg2+ antiport and Na(+)-independent Mg2+ efflux were investigated in erythrocytes of 41 patients with cystic fibrosis and 26 controls. Na(+) independent Mg2+ efflux was unchanged in cystic fibrosis, but a significantly increased activity of Na+/Mg2+ antiport was detected (control: 0.16 +/- 0.02, cystic fibrosis: 0.39 +/- 0.06, Mg2+ efflux, mmol/30 min x 1 cells, mean +/- SEM, p < 0.01). An increased activity of Na+/Mg2+ antiport was only found in patients with severe clinical symptoms. There was no correlation of the increased Na+/Mg2+ antiport to the dF508 genotype. In a patient with increased Na+/Mg2+ antiport, the capacity of this transport system was unchanged 14 weeks after double lung transplantation but reached control values after 53 weeks. The sweat of cystic fibrosis patients with severe clinical symptoms showed a significantly increased Mg2+ concentration (control (n = 12): 0.053 +/- 0.08, cystic fibrosis (n = 9): 0.123 +/- 0.016 mmol/l, mean +/- SEM, p < 0.001). PMID- 7888480 TI - A comparative study of the concentrations of hypoxanthine, xanthine, uric acid and allantoin in the peripheral blood of normals and patients with acute myocardial infarction and other ischaemic diseases. AB - The aim of this study was the elucidation of the role of the xanthine oxidoreductase in the purine metabolism in ischaemic diseases of man. The serum concentrations of hypoxanthine, xanthine, uric acid and allantoin were determined in peripheral blood samples from patients with angina pectoris, cerebral insult and myocardial infarction with thrombolytic therapy and were compared with the concentrations obtained for healthy males and females. No significant differences were observed for the serum hypoxanthine concentrations, xanthine concentrations, the sum (hypoxanthine+xanthine) and the ratio (xanthine/hypoxanthine) between the healthy males, healthy females, the patients suffering from angina pectoris and the patients suffering from cerebral insult. An increase of the serum xanthine concentration in patients with myocardial infarction indicates a significant metabolic involvement of xanthine oxidoreductase in this disease and therefore a possible role in the development of tissue damage in the postischaemic phase due to oxygen radicals generated by the oxidase activity of this enzyme. The serum concentrations of uric acid and allantoin showed no differences between any of the studied groups. Study of the non-enzymatic oxidation of uric acid to allantoin by oxygen radicals, a relevant radical-scavenging mechanism in other diseases, provided no indication of an increased concentration of oxygen radicals due to the xanthine oxidoreductase reaction or other radical-producing mechanisms. PMID- 7888481 TI - Changes in serum, liver and kidneys of cisplatin-treated rats; effects of antioxidants. AB - Cisplatin, a nephrotoxic chemotherapeutic agent, was injected into Sprague Dawley rats, alone or together with cysteine, vitamin E and clonidine. The effects on erythrocyte fragility, serum composition, and kidney and liver enzymes were studied. Cisplatin was administered as two i.p. injections (6 mg/kg body weight) at an interval of 120 hours. The animals were sacrificed 24 hours after the second injection. Erythrocytes were prepared from blood collection with anticoagulant. Serum was prepared from clotted blood, collected without anticoagulant. Kidneys and liver were removed and homogenized, and a supernatant prepared by high speed centrifugation. In cisplatin-treated rats, the serum activities of aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase and alkaline phosphatase were significantly decreased, whereas the activities of isocitric dehydrogenase and glutathione reductase were increased. Also, concentrations of blood urea nitrogen, creatinine, total lipids and magnesium increased while albumin and glucose decreased. Mean osmotic fragility of erythrocytes from cisplatin-treated rats was decreased, while the haematocrit was increased. In the liver, the only change seen was an increased activity of isocitric dehydrogenase. Much greater changes were found in the kidneys, with increased activity of glucose-6-phosphate dehydrogenase and decreased activities of aspartate and alanine aminotransferases, alkaline phosphatase, malic dehydrogenase, sorbitol dehydrogenase and gamma-glutamyltransferase, as well as a decreased phosphorylation to oxidation ratio in the mitochondria, indicating reduced adenosine triphosphate production. Administration of cysteine and vitamin E together with cisplatin partially reversed the uraemia and many of the biochemical changes induced by cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888482 TI - A rapid assay for the quantification of myoglobin: evaluation and diagnostic relevance in the diagnosis of acute myocardial infarction. AB - We evaluated a new, fast, quantitative, turbidimetric assay (TurbiTimeSystem, Behringwerke AG, Marburg, Germany) for the determination of myoglobin concentration in serum. Within-run imprecision (n = 10) was < 3.7% in controls ranging from 81.1 to 621.4 micrograms/l and between-day imprecision (n = 50) was < 6% in controls ranging from 69.5 to 623.4 micrograms/l. The assay is linear over the measuring range and interfering substances such as bilirubin, haemoglobin or haptoglobin do not interfere but triacylglycerol-rich samples are only measurable after brief ultracentrifugation. EDTA- or citrate-treated samples display depressed myoglobin concentration when compared with serum samples. The upper reference limit for apparently healthy individuals (n = 100, 50 female and 50 male) is 61.5 micrograms/l. Comparison with nephelometry revealed a good correlation (r = 0.982) between the two methods with the regression equation: turbidimetric assay = 5.53 + 1.02x nephelometric assay. Serial determination of myoglobin concentration and creatine kinase in 18 patients with proven acute myocardial infarction showed in general an equal diagnostic significance for both analytes. In the first 4 hours after onset of chest pain, the determination of myoglobin can have an advantage, since it is released into the blood stream at an earlier stage, but thereafter myoglobin can lead to false negative diagnosis. Therefore, determination of creatine kinase and its isoenzyme MB is still the diagnostic strategy of choice in the diagnosis of acute myocardial infarction. PMID- 7888483 TI - Sensitivity and specificity of cocaine metabolite screening in view of the analytical performance of a fluorescence polarisation immunoassay. AB - Immunoassays for drug screening are called 'qualitative' or 'semiquantitative' by the manufacturers of these tests and they urgently recommend the user to verify each result exceeding the recommended cut-off value by a confirmation test. For therapeutic drug monitoring assays or for the determination of tumour markers or hormones, similar recommendations are not given, although the same analytical technologies are used for these assays. A scientific validation of the commonly used cut-off values recommended by the official bodies (e.g. NIDA, DoD) is unfortunately not described in the accessible scientific literature. A solution to this problem was sought by evaluating the analytical characteristics of the assay and determining the diagnostic validity of the test using an immunoassay for the cocaine metabolite as an example. Hundred urine samples from people suspected of cocaine abuse and 50 urine samples from patients unlikely to have consumed cocaine were analysed in triplicate with a commercially available fluorescence polarisation immunoassay. From this data we assessed the analytical variance of the assay using the computer program of Sadler & Smith (Clin. Chem. 36 (1990), 1346-1350). Using the functions provided, we calculated the limit of detection (LD) and the lower limit of quantification (LLQ) as well as the so called power of definition (PD) using a recently published method (Gautschi et al., this journal 31 (1993), 433-440). This procedure is mathematically well defined, uses no artificial standards or calibrators and is in compliance with IFCC recommendations. A clearly defined assessment of the diagnostic performance of an assay is of utmost importance for the discussion of adequate decision levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888484 TI - Fitting response curves for radioimmunoassays or immunoradiometric assays. AB - The paper describes non-linear regression methods for the evaluation of radioimmunoassay or immunoradiometric assay data. The underlying model is an overdispersed Poisson process with four regression line parameters and one parameter related to the overdispersion of the variance. A generalized least squares algorithm is described for the parameter estimation of non-contaminated data. In the presence of outliers in Y-direction, the results are improved by a winsorized version of the generalized least-squares method. PMID- 7888485 TI - Production of chimeric pigs and the analysis of chimerism using mitochondrial deoxyribonucleic acid as a cell marker. AB - Two injection methods were examined for making chimeras between Chinese pigs (Meishan) and European pigs (Landrace or Landrace x Large White). Furthermore, mitochondrial DNA (mtDNA) polymorphism was detected as a cell marker for the analysis of chimerism. In the first experiment, blastomeres were transplanted into embryos at the 4-16-cell stage. Of 41 transplanted embryos transferred into 3 females, 12 were single-colored, but no overt chimeras were obtained. Judging from coat color and mtDNA in white blood cells, 2 piglets in 2 litters were derived from injected blastomeres, and 10 piglets in 3 litters were derived from recipient blastomeres. In the second experiment, inner cell mass cells of Day 6 Landrace embryos were injected into blastocoels of Day 6 Meishan embryos. Of 35 injected embryos transferred into 3 females, 2 overt chimeras of each sex were obtained in a single litter. In the overt male chimera, mtDNA clearly showed chimerism in spleen, pancreas, brain, kidney, lung, liver, heart, testis, and small intestine. The overt female chimera showed chimerism not only in blood but also in germ line according to a progeny test. No chimerism was detected in any of the 21 single-colored piglets in the second experiment. PMID- 7888486 TI - Development of an antifertility vaccine for pets based on active immunization against luteinizing hormone-releasing hormone. AB - Male dogs and cats were immunized against LHRH in order to evaluate the feasibility of an immunological approach to pet contraception. In the first study, dogs were immunized with 100, 500, or 2500 micrograms of LHRH conjugated to tetanus toxoid. A significant decline in serum testosterone (T) levels was observed in all immunized dogs, reaching castration levels in some animals by Week 4 and remaining suppressed in all the immunized dogs through the course of the study. Testicular histology suggested arrest of spermatogenesis (infertility). The effects of "immunological castration" were reversible (study 2): steroidogenesis suppressed by "immunological castration" was restored as antibody titers declined. Effective antibodies were rapidly reinduced in dogs by a single injection of LHRH1-TT. In contrast, the level of antibodies induced in male cats (study 3) was not sufficient for "immunological castration." The conclusion was that active immunization against LHRH could provide a cost effective, nonsurgical, reversible means to control the fertility of companion animals. PMID- 7888487 TI - The postpartum llama: fertility after parturition. AB - Fertility was evaluated at various times during the postpartum period in the llama. Fifty-six parous female llamas chosen at random were bred at 10, 20, and 30 days postpartum with six intact males. Half of the females copulated only once and the other half twice within an interval of 24 h. Ovarian activity was monitored by ultrasonography and analysis of urinary estrone sulfate and pregnanediol glucuronide (PdG). At the time of copulation, all females had developed ovulatory-size follicles. Ovulation was confirmed by the presence of a CL at 8 days after breeding and PdG concentrations > 1 ng/mg creatinine (Cr). Conception was defined as PdG concentrations > 1 ng/mg Cr at 15 days after breeding and the presence of a CL. Pregnancy was defined as the presence of a CL, PdG concentrations > 1 ng/mg Cr and an embryonic vesicle 20 days postbreeding. There were no significant differences in the proportion of females ovulating after breeding at different times postpartum; however, conception and pregnancy were significantly greater in females bred at Day 20 or 30. Ovarian follicle size was significantly larger at 30 days (9.1 mm) than at 10 and 20 days (7.9 and 8.8 mm, respectively) of breeding, with no difference in concentrations of estrone sulfate. The proportion of females conceiving as a result of breeding at 10 days postpartum (6 out of 10) was significantly less than for females bred at 20 (13 out of 15) or 30 days (16 out of 18).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888488 TI - Regulation of intracellular calcium in the mouse egg: calcium release in response to sperm or inositol trisphosphate is enhanced after meiotic maturation. AB - Fertilization of the immature, prophase I-arrested mouse oocyte produces multiple Ca2+ transients similar to those of the mature, metaphase II egg; however, the first Ca2+ transient is much lower in amplitude and shorter in duration. In contrast to prophase I-arrested oocytes, maturing oocytes fertilized after germinal vesicle breakdown have first Ca2+ transients similar to those of mature fertilized eggs. Immature, prophase-arrested oocytes release less Ca2+ in response to injection of inositol 1,4,5-trisphosphate (IP3) than eggs. At high concentrations, the sulfhydryl reagent, thimerosal (200 microM), causes Ca2+ oscillations in eggs and produces similar oscillations in oocytes. A lower concentration of thimerosal (25 microM) does not cause Ca2+ oscillations, but does sensitize IP3-induced Ca2+ release in both eggs and oocytes, since IP3 induced Ca2+ release is enhanced in the presence of 25 microM thimerosal. Incubation of oocytes in 25 microM thimerosal before injection of 2.2 microM IP3 causes oocytes to release as much Ca2+ as is released in eggs injected with 2.2 microM IP3. These results indicate that immature mouse oocytes possess intracellular stores of releasable Ca2+ similar in size to Ca2+ stores in eggs; however, these stores are less sensitive to IP3. Development of the IP3-induced Ca2+ release mechanism may be an important component of maturation; at fertilization of the egg, Ca2+ must be elevated to levels sufficient to activate further development and establish a block to polyspermy. Mouse oocytes appear to develop an increased sensitivity to IP3 during the course of oocyte maturation. PMID- 7888489 TI - Differences in the role of cyclic adenosine 3',5'-monophosphate during capacitation of bovine sperm by heparin or oviduct fluid. AB - Capacitation is an important maturational event in the life of a spermatozoan that allows the sperm to undergo a stimulus-induced acrosome reaction. Bovine sperm can be induced to undergo capacitation in vitro by heparin or oviduct fluid, and capacitation can be inhibited by glucose. We found that glucose did not interfere with 3H-heparin binding to sperm. Glucose inhibition of capacitation could be reversed in a dose-dependent manner by 8-bromo-cAMP or by the phosphodiesterase inhibitors isobutylmethylxanthine or caffeine, with ED50S of 25, 32, and 183 microM, respectively. The maximal effect of 8-bromo-cAMP on capacitation was during the first 2 h of a 4-h incubation. Sperm cAMP increased during capacitation with heparin from an initial value of 4.1 +/- 0.1 to 7.3 +/- 1.1 pmol cAMP/20 x 10(6) sperm at 4 h of incubation. Control sperm cAMP at 4 h increased only to 4.9 +/- 0.8 pmol cAMP/20 x 10(6) sperm. There were both similarities and differences in the characteristics of capacitation by heparin or oviduct fluid. Both glucose and protamine sulfate were found to suppress the heparin-dependent cAMP increase and inhibit capacitation. Capacitation by oviduct fluid was inhibited by either glucose or protamine sulfate. A small increase in sperm cAMP was associated with capacitation by oviduct fluid but was not affected by glucose or protamine sulfate. PMID- 7888490 TI - Regulation of connexin26 and connexin43 expression in rat endometrium by ovarian steroid hormones. AB - A distinct spatial and temporal pattern of connexin26 and connexin43 (cx26 and cx43) expression was observed in the rat endometrium in response to embryo implantation; however, connexin expression was suppressed during the preimplantation period. Pseudopregnant rats did not show connexin mRNA, while artificial decidualization induced by a scratch led to a strong expression of cx26 and cx43 in the endometrium of these animals. In order to examine the regulatory effects of ovarian steroid hormones on connexin expression, ovariectomized rats were treated with progesterone (P) and/or estradiol-17 beta (E2). Untreated, ovariectomized animals expressed mRNA for cx43, but not for cx26. Endometrial expression of mRNA for both connexins was strongly enhanced by E2 treatment; immunolabeling revealed protein for cx26 in the uterine luminal epithelial cells and for cx43 in the uterine stromal cells. P treatment, either alone or in combination with E2, suppressed expression of connexin mRNA. P suppression in the presence of E2 was reversible when P was withdrawn. When administered on Days 0-2 of pregnancy, the antiprogestin onapristone inhibited the effect of P and gave rise to strong expression of both connexin transcripts. These results demonstrate that expression of cx26 and cx43 in the rat uterine endometrium is differentially regulated by E2 and P during early pregnancy. PMID- 7888491 TI - Early embryonic development in the Djungarian hamster (Phodopus sungorus) is accompanied by alterations in the distribution and intensity of an estrogen (E2) dependent oviduct glycoprotein in the blastomere membrane and zona pellucida and in its association with F-actin. AB - The luminal environment of the estrogen (E2)-dominated mammalian oviduct generates and sustains the environment in which the first embryonic cleavages take place. The objective of this study was to determine, by use of an antiserum against an E2-dependent sheep oviduct secretory glycoprotein (M(r) 90,000 92,000), whether the E2-dominated and pregnant oviduct of the Djungarian hamster (Phodopus sungorus) releases an antigenically related protein. If the protein was present, a secondary objective was to define its fate and association with filamentous-actin (f-actin) and chromatin patterns in early cleavage-stage embryos. Oviduct flushings containing embryos (1-cell fertilized, 2-, 4-, and 8 cells), and uterine flushings (> 16 cell embryos) were obtained from pregnant hamsters. Embryos were removed from flushings, and oviduct secretions were analyzed by Western blotting. The zona pellucida was removed with acid Tyrode's solution from approximately half of the 2-, 4-, and 8-cell embryos. Zona-intact and zona-free embryos were then fixed and subjected to triple immunofluorescence staining with an antiserum to the sheep oviduct protein, rhodamine phalloidin, and Hoechst 33258. An antigenically related protein M(r) 200,000) was detected in oviduct secretions of E2-treated, ovariectomized, and pregnant hamsters, and not in secretions from ovariectomized controls. In the zona pellucida of 1- and 2 cell embryos, the oviduct protein displayed an intertwining, reticular organization that was replaced by a diffuse and more intense accumulation in 4-, 8-, and > 16-cell embryos. In 2-cell embryos, punctate foci of the oviduct protein were distributed unevenly over the apical blastomere plasma membrane, forming patches in regions of f-actin exclusion, which were absent at later development stages. At the 4- and 8-cell stage of development, as blastomeres lost their spherical form by minimizing intercellular spaces, the oviduct protein took on a polarized arrangement and was intensely concentrated on membrane areas involved in cell-cell contact that were also the focus of f-actin. These data show that in early cleavage-stage hamster embryos, the intensity and pattern of staining for an E2-dependent oviduct protein (M(r) 200,000) that is released into the oviduct lumen during embryo transport can be distinguished on the basis of membrane f-actin display and blastomere number and shape. These events may mediate cellular processes related to blastomere cleavage, shaping, and/or adhesion that occur in the oviduct. PMID- 7888492 TI - Comparison of binding affinity of oxytocin antagonists to human and rat uterine oxytocin receptors and their correlation to the rat uterine oxytocic bioassay. AB - One of the primary methods used to screen the development of oxytocin antagonists (OTAs) is the rat oxytocic bioassay. The purpose of this study was to determine whether the rat oxytocic bioassay is a good predictor of binding affinity to human and rat uterine oxytocin receptors (OTr). The binding affinities of five OTAs to human and rat uterine OTr were determined and correlated with pA2 values derived from the rat uterine oxytocic bioassay. Human uterine myometrial tissue was obtained from patients at the time of cesarean section. Rat uterine tissue for the OTr assay was taken at Day 21 of pregnancy. OTr assays were accomplished by isolating uterine cell membranes and performing saturation analysis with cold OTAs and tritium-labeled oxytocin. The association constants (Ka; 10(+8)/M) were calculated by nonlinear curve-fitting techniques. The Ka for the five OTAs (Mpa1 OT, Antag I, L366948, Antag II, and Antag III), as estimated from the human OTr assay, were 0.55, 0.60, 2.27, 1.91, and 47.20, respectively. Ka estimates obtained through use of rat uterine membranes were 0.51, 1.16, 5.89, 2.03, and 24.40, respectively. Correlation of the log10 of the rat oxytocic bioassay results with those of the rat and human OTr assay was 0.94 and 0.98, respectively (p < 0.01). Antag III was approximately 55, 48, and 90 times more potent than Mpa1-OT as determined by the rat bioassay and rat and human uterine OTr assays, respectively. Mpa1-OT is an OTA that is currently undergoing clinical evaluation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888493 TI - Interferon gamma induces intercellular adhesion molecule-1 on murine midterm trophoblast and enhances susceptibility to specific lysis by paternally directed allo-immune cytotoxic T cells. AB - Expression and function of intercellular adhesion molecule-1 (ICAM-1) on murine trophoblast cells and its regulation by interferon gamma (IFN-gamma) were investigated. Flow cytometry was used to detect ICAM-1 and class I major histocompatibility complex (MHC) antigen expression, while a 51Cr release assay was used to investigate the role of ICAM-1 in cytotoxic T lymphocyte (CTL) mediated lysis and the effect of anti-ICAM-1 antibody blockade on lysis. We found that murine trophoblasts cells from midterm pregnancy (Day 14 postcoitum) express low or undetectable ICAM-1 and MHC antigens but that these are readily inducible by IFN-gamma. Untreated cells resisted lysis by allospecific CTL however, after treatment with IFN-gamma for 72 h, these trophoblasts were readily susceptible to lysis by allospecific CTL. The lysis was significantly reduced by anti-ICAM-1 antibody blocking. This finding which indicates that ICAM-1 can take part in CTL mediated lysis of midterm trophoblast, has potentially important implications in vivo for the immunological relationship between mother and fetus. PMID- 7888494 TI - Pregnancy in B-cell-deficient mice: postpartum transfer of immunoglobulins prevents neonatal runting and death. AB - Mice lacking functional B cells because of a genetic deletion of the mu chain (IgM) gene were used to investigate the role of perinatal and postnatal transfer of maternal IgG in neonatal growth. Our results confirmed that immunoglobulin (Ig)-deficient mice successfully complete pregnancy and deliver healthy offspring. However, neonates nursed by Ig-deficient mothers showed growth retardation (runting) and high mortality during their first 10 days of life. This fatal course was seen whether or not the neonates were Ig-deficient. Cross switching litters from phenotypically normal mothers to Ig-deficient mothers immediately after birth showed that perinatal Ig transfer normalized neonatal development for 10 days, but was not sufficient to sustain survival during the later part of the neonatal period. On the other hand, all Ig-deficient litters nursed by normal foster mothers showed normal development and 0% neonatal mortality. Administration of mouse IgG to an Ig-deficient mother or a neonate during the first critical week prevented runting. We assume that the growth- and health-promoting effects of IgG during early neonatal life are attributable mainly to the transfer of passive immunity to environmental pathogens. However, the finding that monoclonal IgG antibodies also enhanced neonatal growth and survival suggests that IgG-dependent growth-promoting mechanisms could be involved as well. PMID- 7888495 TI - Effects of photoperiod, pinealectomy, and melatonin implants on testicular development in juvenile Siberian hamsters (Phodopus sungorus). AB - When transferred from a long to short photoperiod, Siberian hamsters (Phodopus sungorus) undergo a number of physiological and morphological changes including suppression of gonadal activity, a change in pelage color, a decrease in body weight, and, in response to a simultaneous decrease in ambient temperature, physiological changes associated with the induction of daily torpor. All these functions can be affected by photoperiod and melatonin treatment. To investigate the interactive effects of photoperiod, pinealectomy, and melatonin on gonadal development, two experiments were performed using juvenile Siberian hamsters. In experiment 1, animals born in a long photoperiod (16L:8D) either remained in a long photoperiod or were transferred to a short photoperiod (8L:16D) from 15 days of age, when surgeries (pinealectomy and/or melatonin implantation) were performed. Testicular development was inhibited in all animals bearing melatonin implants irrespective of the presence or absence of the pineal gland. Pinealectomy blocked the inhibitory effect of short photoperiod on maturation of the reproductive system. Therefore, the pineal gland must be involved in the short photoperiod- induced inhibition of testicular maturation of juvenile Siberian hamsters. In experiment 2, a similar experimental design was employed except that the hamsters were born and raised to 15 days of age in 8L:16D. Exogenous melatonin, pinealectomy, or both retarded gonadal development in hamsters born in 8L:16D and transferred on Day 15 of age to 16L:8D. All hamsters maintained in a short photoperiod had small testes irrespective of the presence of absence of the pineal gland or of melatonin implants. Hamsters transferred to a long photoperiod after pinealectomy and/or melatonin implantation had small testes compared to those of the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888496 TI - Co-localization of placental lactogen-I, placental lactogen-II, and proliferin in the mouse placenta at midpregnancy. AB - This study was undertaken to determine whether mouse placental lactogen (mPL)-I, mPL-II, and proliferin (PLF) are expressed by the same population of placental giant cells at midpregnancy. Tissue sections from Day 9 of pregnancy were analyzed by double immunofluorescence staining. Sections were stained for PLF by use of a rhodamine-conjugated second antibody, and for mPL-I or mPL-II by use of a fluorescein-conjugated second antibody. All three proteins were present in most of the same giant cells. The distribution of mPL-I and PLF among giant cells in vitro was also examined. When placental cells from Day 7 of pregnancy were cultured for 5 days, > 90% of the cells that immunostained for mPL-I also immunostained for PLF on the first 3 days of culture. Thereafter, the percentage of cells that contained both proteins declined rapidly while the percentage that contained only PLF increased, suggesting continued differentiation of the cells in vitro. These data demonstrate that the same trophoblast giant cells express mPL-I, mPL-II, and PLF simultaneously at midpregnancy, suggesting that their gestational profiles in maternal blood during this period result at least partly from changes in gene expression in one population of cells and not from differentiation of several subsets of giant cells, each expressing only one member of the gene family. PMID- 7888497 TI - Steroidogenic and morphogenic characteristics of human peritubular cells in culture. AB - We have explored the morphogenic and functional characteristics of human peritubular cells originating from seminiferous tubule (ST) fragments isolated from the testes of two prepubertal patients with the androgen insensitivity syndrome. These ST were cultured in Dulbecco's Modified Eagle's Medium-Ham's F-12 supplemented with antibiotics, transferrin, hydrocortisone, vitamin E, and 3% fetal bovine serum. A centrifugal growth of elongated fibroblast-like cells peripheral to the ST explants was observed. Muscle-specific actin and 3 beta hydroxysteroid dehydrogenase were evident in the peritubular area and in the elongated cells growing from the tubules. Histochemistry was negative in the tubules themselves, revealing the mixed nature of these cultures. The ST fragments were lost after subculturing, leaving a homogeneous monolayer of fibroblast-like cells. The steroidogenic potential of these cells was demonstrated by the secretion of testosterone (T) to the culture medium. T secretion was stimulated by hCG in a time-dependent fashion (patient 1: Day 11, 84% and Day 15, 200%; patient 2: Day 8, 73% and Day 11, 32% over basal). FSH also stimulated T secretion (patient 1: Day 5, 136% and Day 8, 89%; patient 2: Day 8, 117% and Day 11, 129% over basal). Furthermore, T secretion by these cultures was 100% higher than that observed in mesenchymal cells obtained from the testicular intertubular space in the same patient. Spontaneous T secretion and hormone responses declined progressively to cease by 25 days in culture. These results suggested the involvement of Sertoli cell (SC)-secreted factor(s) in the regulation of T secretion by peritubular cells. In order to further explore possible paracrine interactions between peritubular and Sertoli cells, we carried out heterologous cocultures with rat SC. After 72 h a striking redistribution of both cell types was observed with the formation of cord-like structures. Ultrastructural examination of these cords showed the formation of a basement membrane between epithelial (Sertoli) and mesenchymal cells of peritubular origin. No resumption of T secretion was observed, but an increase in androgen binding protein (ABP) production by rat SC under basal (37%) and FSH-stimulated (52%) conditions was evident. Our results show that in the human peritubular compartment, cells exist that can alternatively express steroidogenic functions, associate with SC in a specific mesenchymal-epithelial interaction, and exert regulatory influences on ABP secretion by SC. In addition they indicate that communicating events in the testis are preserved throughout evolution. PMID- 7888498 TI - Mouse placental cells secrete immunoreactive growth hormone-releasing factor. AB - The initial objective of this study was to establish a placental cell culture system in which the secretion of mouse growth hormone-releasing factor (mGHRF) could be examined during a several-day period. To determine when during pregnancy placental cells begin to express mGHRF, Northern blot analysis was carried out on total RNA from placentas collected on Days 6, 9, 11, 13, 15, 17, and 18 of pregnancy. Mouse GHRF mRNA could be detected as early as Day 11 of pregnancy. Its steady-state levels increased to maximum values on Days 15-17 and then declined slightly on Day 18. Placentas from Day 12 of pregnancy were selected for cell culture. The basal zone and labyrinth were dispersed in collagenase, and the cells were fractionated on a Percoll gradient. Two bands of cells were selected for further study. Both released significant amounts of immunoreactive mGHRF during a 5-day culture period. Effects of prolonged exposure of the cells to 8 bromo-cAMP and to agents that elevate intracellular cAMP concentration were then examined. Treatment of the cells with 0.5 mM 8-bromo-cAMP resulted in a significant decrease in the mGHRF concentration of the medium by the second day of culture. Mouse GHRF secretion was also inhibited by treatment of the cells with 100 ng/ml cholera toxin or 0.1 mM forskolin. The effect of 8-bromo-cAMP was concentration-dependent, with 0.1 mM being the lowest concentration that was active. 8-Bromo-cAMP treatment also reduced the steady-state level of mGHRF mRNA in the cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888500 TI - Paternal influence on S-phase in the first cell cycle of the bovine embryo. AB - The objective of this study was to determine whether the initiation and length of the zygotic S-phase differs for embryos sired by bulls demonstrating high versus low fertility in vivo. Bovine oocytes were matured in vitro for 24-27 h and fertilized with frozen-thawed bovine semen. Six bulls that differed in fertility level were used in the study. The bulls were classified into two groups: those demonstrating high fertility in vivo (in vivo high-fertility bulls; n = 3), with a group mean +/- SEM lifetime nonreturn rate of 78 +/- 2%, and those demonstrating low fertility in vivo (low-fertility bulls; n = 3), with a group mean +/- SEM nonreturn rate of 69 +/- 1%. The S-phase in zygotes was identified by means of an immunocytochemical technique after pronuclear-stage zygotes were labeled with 5'bromo-2'deoxyuridine (BrdU). To visualize all pronuclei, presumptive zygotes were also stained with propidium iodide. In the first experiment, zygotes were labeled with BrdU at 2-h intervals from 8 to 20 h after sperm addition. There were no differences between bull fertility groups in the time course of pronuclear formation (p > 0.05). The beginning of S-phase was earlier in zygotes sired by high- compared to low-fertility bulls (p < 0.05). The end of S-phase was not affected by sire fertility group (p > 0.05). In the second experiment, zygotes were labeled with BrdU continuously from 8 to 20 h after sperm addition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888499 TI - Human SP-10: acrosomal distribution, processing, and fate after the acrosome reaction. AB - SP-10 is a testis-specific acrosomal protein that has been detected in several species including humans. Extracts from whole human testis and epididymal, ejaculated, and capacitated sperm were analyzed by Western blot for SP-10 polypeptides. The testis extracts contained a full-length SP-10 protein at approximately 45 kDa as well as other immunoreactive SP-10 peptides at 32, 30, 28, and 26 kDa. Extracts from epididymal, ejaculated, and capacitated sperm contained several immunoreactive SP-10 peptides that co-migrated with the 32-26 kDa SP-10 peptides in the testis extracts. Epididymal, ejaculated, and capacitated sperm extracts did not contain the 45-kDa SP-10 peptide observed in testis extracts, but did contain immunoreactive SP-10 peptides from 25 to 18 kDa that were not detected in testis extracts. These results indicate that a full length 45-kDa SP-10 precursor protein is present in the testis and that SP-10 peptides of 32, 30, 28, and 26 kDa result from proteolytic processing of the SP 10 precursor protein in the testis and/or alternative splicing. In addition, SP 10 peptides of 25-18 kDa were first detected in extracts of caput epididymal sperm and probably resulted from the proteolytic processing of the 45- and 32-26 kDa SP-10 peptides in the initial segment or caput epididymidis. Also, no additional SP-10 bands were detected in extracts of cauda epididymal, ejaculated, or capacitated sperm, suggesting that no further processing of the 32-18-kDa SP 10 peptides occurred during epididymal transit, ejaculation, and capacitation. Electron microscopic immunocytochemical observations of epididymal, ejaculated, and capacitated sperm revealed that colloidal gold labeling of SP-10 was most abundant within the principal segment and posterior bulb of the equatorial segment of the acrosome, while the colloidal gold labeling of SP-10 was sparse in the anterior equatorial segment of the acrosome. After a follicular fluid-induced acrosome reaction, SP-10 was detected on the inner acrosomal membrane in the equatorial segment and was associated with hybrid vesicles. This localization after the acrosome reaction is consistent with the hypothesis that SP-10 may be involved in sperm-zona binding or penetration. PMID- 7888501 TI - Role of zinc during hamster sperm capacitation. AB - Zinc stabilizes somatic cell membranes and DNA, inhibits respiration, is present in high concentrations in the male reproductive tract, and may stabilize sperm during storage and ejaculation. Zinc removal from sperm may be necessary to prepare sperm for fertilization (capacitation). Incubation with Zn2+ chelators, e.g., D-penicillamine, can capacitate hamster sperm (Andrews and Bavister, Gamete Res 1989; 23:159-70). In the present study, the Zn(2+)-specific fluorochrome N-(6 methoxy-8-quinolyl)-p-toluenesulfonamide (TSQ) and the vital stain propidium iodide were used to assess the zinc content of live hamster sperm with flow cytometry before and after capacitation. Capacitation was monitored with a salt stored zona pellucida penetration assay or the occurrence of spontaneous or induced (with lysophosphatidylcholine) acrosome reactions. The effect of added zinc on sperm capacitation was also evaluated. Image Analysis was used to determine the subcellular location of zinc (TSQ fluorescence) and atomic absorption to determine whether the total zinc content of sperm changes during capacitation. Sperm incubated under non-capacitating conditions had high TSQ fluorescence and could not penetrate zonae pellucidae. Sperm incubated under capacitating conditions (plus BSA or D-penicillamine) were zinc-depleted (low fluorescence) and penetrated 90% or 78% of zonae, respectively. Image analysis showed a significant reduction in zinc in the acrosomal region during capacitation with BSA, but this did not correlate with the occurrence of spontaneous acrosome reactions. The atomic absorption data showed that the total zinc content of sperm was reduced by 44% or 40% when sperm were incubated under capacitating conditions (BSA or D-penicillamine, respectively). Zona pellucida penetration was completely inhibited when zinc was present throughout the capacitation period but not when it was added at the end of incubation. These data indicate that removal of zinc from hamster sperm is correlated with capacitation and may play a key regulatory role in this process. PMID- 7888502 TI - Luteinizing hormone has a role in development of fully functional corpora lutea (CL) but is not required to maintain CL function in heifers. AB - We tested the hypothesis that endogenous pulses of LH have a role in development and maintenance of CL during the estrous cycle of the bovine female. Twenty heifers were synchronized to estrus by treating two times with prostaglandin F2 alpha 11 days apart (Day 0 = behavioral estrus). Heifers were then randomly assigned to one of four treatments (n = 5/group). Heifers were treated with an antagonist to LHRH (LHRH-Ant; N-Ac-D-Nal[2]1,4Cl-D-Phe2,D-Pal[3]3,D-Cit6,D-Ala10- LHR H; 10 micrograms/kg body weight) or vehicle (5% mannitol) once every 24 h: 1) LHRH-Ant Days 2-7, 2) LHRH-Ant Days 7-12, 3) LHRH-Ant Days 12-17, 4) no LHRH-Ant (control). Blood samples were collected from the jugular vein twice daily on Days 0-24, and area under the profile of progesterone in circulation during the luteal phase of the estrous cycle was characterized from the start of each treatment period until the demise of CL or Day 24, whichever came first. Luteolysis was considered to have occurred when three consecutive samples contained less than 1 ng progesterone/ml plasma. Areas under the profile of progesterone in circulation during the luteal phase of the estrous cycle were compared to those of heifers from the control group for the same period. LHRH-Ant treatment diminished LH pulses in all treatment groups compared to control (p < 0.05). Treatment with LHRH-Ant on Days 2-7 diminished function of CL (3.72 +/- 0.93 vs. 7.36 +/- 1.02 units, respectively; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888503 TI - Inhibition of in vivo fertilization by active immunization of male hamsters against a 26-kDa sperm glycoprotein. AB - We have identified a 26-kDa (P26h) epididymal hamster sperm glycoprotein with a species-specific affinity for zona pellucida glycoprotein. Two immunological procedures have been used to document the biological function of this sperm component; active immunization of males against P26h and inhibition of sperm-zona pellucida binding in vitro by anti-P26h antibodies. The immunized male hamsters produced circulating antibodies specific to P26h. Indirect immunofluorescence studies showed that these antibodies bind to the surface of the sperm covering the acrosome. These males were mated with superovulated females, and although spermatozoa were recovered from the genital tract, none of the 194 oocytes recovered were fertilized. In contrast, control males immunized with hamster albumin fertilized 97.4% of the oocytes. Unlike control spermatozoa, those recovered from the cauda epididymidis of males immunized with P26h were characterized by the presence of antibodies at the surface of the acrosome. To establish whether the inhibition of in vivo fertilization by active immunization was occurring at the level of sperm-zona pellucida interaction, a polyclonal antiserum against P26h was raised, and the IgG fraction was added to an in vitro sperm-zona pellucida assay. Compared to the preimmune serum, the IgG inhibited the binding of spermatozoa in a dose-dependent manner. The Fab fragments generated from these IgGs were almost as efficient in inhibiting the binding. These results are discussed with regard to a possible function of P26h in hamster gamete interaction. PMID- 7888504 TI - A reduced proportion of luteinizing hormone (LH)-releasing hormone neurons express Fos protein during the preovulatory or steroid-induced LH surge in middle aged rats. AB - Results of previous studies suggest that altered patterns of LHRH neurosecretion contribute to attenuated LH surges and the eventual cessation of ovulation in aging female rats. The present study compared evidence of LHRH neuronal activation in conjunction with the preovulatory and steroid-induced LH surge in young and middle-aged animals to determine whether age-related alterations could be detected. Double immunocytochemical protocols were used to colocalize LHRH and the protein product of the proto-oncogene c-fos, which increases within the nucleus of LHRH neurons in association with spontaneous or induced LH surges. The mean proportion of LHRH neurons containing immunoreactive Fos was higher in the brains of young compared to middle-aged females in association with both the preovulatory (p < 0.01) and the steroid-induced LH surge (p < 0.001). The time course of activation of LHRH neurons was delayed in the brains of aging females, and the proportion of double-labeled LHRH neurons remained elevated longer in the brains of young compared to middle-aged steroid-treated females. Moreover, regional differences in LHRH neuronal activation were observed both within and between age groups. The data presented suggest that reduced LHRH neuronal activation may contribute to the attenuation and eventual loss of preovulatory LH surges in middle-aged female rats. PMID- 7888505 TI - Prenatal inhibition of aromatase activity affects luteinizing hormone feedback mechanisms and reproductive behaviors of adult guinea pigs. AB - The necessity of brain aromatization for sexual differentiation was investigated by treating pregnant guinea pigs with an aromatase inhibitor, 1,4,6 androstatriene-3,17-dione (ATD), from Day 30 to Day 55 of gestation. In postnatal Week 16, subjects were gonadectomized, and blood samples were collected after treatment with 10 micrograms estradiol benzoate (EB), used to elicit an LH surge; subjects were subsequently treated with GnRH to test pituitary responsiveness. Plasma samples were assayed for LH by RIA. Prenatal ATD treatment did not affect the organization of the LH surge mechanism in either male or female subjects. All animals, regardless of sex or treatment, released LH after GnRH treatment, but the responsiveness of the gonadotroph to GnRH was attenuated in both males and females treated with ATD in utero. In addition, a significant sex difference in the pattern of LH released in response to a GnRH challenge was found. ATD-treated animals did not respond to the negative feedback actions of EB on LH secretion (p < 0.05), and the percentage of males displaying lordosis behavior was greater in this group than in controls (p < 0.05). Mounting behavior and lordosis behavior of females were not significantly affected by treatment. These data demonstrate a need for estrogen in the organization of brain areas that mediate negative feedback control of LH in both sexes and lordosis behavior in the male guinea pig. The organization of positive feedback mechanisms for controlling LH seems to be under androgenic control. Our data also suggest that the responsiveness of the gonadotroph to GnRH action is developmentally coordinated by prenatal estrogen and is sexually differentiated. PMID- 7888507 TI - Identification and distribution of tumor necrosis factor alpha receptors in pig corpora lutea. AB - This study examined whether the pig CL contains specific tumor necrosis factor alpha (TNF alpha) receptors and compared the binding affinities and capacities of small and large cell membranes. Aliquots of membranes, isolated from intact or dispersed luteal tissue, were homogenized, and membrane protein content was quantified. Luteal membranes were assayed for specific TNF alpha binding by displacement analysis, with use of [125I]TNF alpha and varying concentrations of unlabeled TNF alpha. Preliminary experiments demonstrated that TNF alpha binding was maximal after incubation at 22 degrees C for 180 min. In addition, [125I]TNF alpha binding was displaced by TNF alpha, but not by other cytokines. Small cell membranes contained a TNF alpha binding site with an affinity (Kd = 11.6-19 nM) different (p < 0.05) from that of the binding site on large cell membranes (Kd = 56.2-99.6 nM). TNF alpha binding capacities were similar in small and large cell membranes. These data demonstrate that pig CL contain specific, saturable TNF alpha binding sites. The higher-affinity binding sites were localized in the small cell population, which contains predominantly endothelial cells and small luteal cells, suggesting that TNF alpha acts primarily on one or both of these cell types within the CL. PMID- 7888506 TI - Lysis of porcine trophoblast cells by endometrial natural killer-like effector cells in vitro does not require interleukin-2. AB - Cells with cytotoxic activity against the cell line K562 and expressing perforin have been demonstrated in endometrial cells isolated from pigs early in pregnancy. This study was designed to determine whether porcine trophoblast cells were susceptible to these endometrial effector cells in vitro. Pregnant gilts (n = 8) were slaughtered between Days 17 and 20 of gestation. Immediately after slaughter, both the endometrial effector cells and trophoblast cells were isolated enzymatically from each animal. Enzymatically dispersed endometrial cells were further fractionated by size at unit gravity, whereas trophoblast cells were enriched by discontinuous density centrifugation on Percoll. Cytolytic activity was evaluated against Na2 51CrO4-labeled trophoblast and K562 cells. Comparison was made between freshly prepared and interleukin-2 (IL-2)-stimulated effector cells. The effect of prostaglandin E2 (PGE2) was tested by including it directly in the 51Cr-release assay. The results indicated that porcine trophoblast cells, like K562 cells, could be recognized and directly lysed by endometrial effector cells. Preculture of effector cells with IL-2 was not required for target lysis but enhanced their cytolytic activity against both trophoblast and K562 targets. In contrast, PGE2 exhibited highly suppressive effects on the cytotoxic activity of both freshly isolated and IL-2-stimulated endometrial effector cells. Conjugate assays demonstrated the binding of trophoblast and K562 targets by effector cells of similar morphology. Cold-target inhibition assays suggested that the effectors in porcine endometrial cell preparations that killed trophoblast and K562 cells were the same NK cell-like population. PMID- 7888508 TI - Bioactive follicle-stimulating hormone concentrations in plasma during the estrous cycle of the ewe. AB - Bioactive FSH (B-FSH) concentrations in plasma were determined during the ovine estrous cycle by means of an in vitro bioassay. The concentrations of B-FSH were elevated during and after the preovulatory LH surge and were significantly (p < 0.05) lower during the late-luteal to mid-follicular phases compared with the mid luteal phase. A significant (p < 0.05) increase in B-FSH was found about 36 h before the LH surge, at a time when the immunoreactive FSH (I-FSH) concentrations were low and unchanged. The plasma B/I ratio for FSH was relatively constant during the luteal phase; it then increased significantly (p < 0.05) before the LH surge and decreased again at the time of the LH surge itself. Pulsar analysis showed that there were 4 peaks of B-FSH throughout the estrous cycle with 2 during the luteal phase, 1 after the LH surge, and the other either during the follicular phase or associated with the LH surge. For I-FSH there were approximately 8 peaks throughout the cycle with 4 during the luteal phase, 2 after the LH surge, and 1 each during the follicular phase and the preovulatory LH surge. There was a weak negative correlation between I-FSH and immunoreactive inhibin (I-inhibin) during most of the estrous cycle, but B-FSH and the B/I ratio were only correlated (negatively) with I-inhibin in the 24 h before the preovulatory LH surge. These findings suggest that there are significant changes in the circulating isoforms of FSH during the ovine estrous cycle that may affect the growth of antral follicles developing towards ovulation. PMID- 7888509 TI - In vitro microdialysis of the ovine corpus luteum of pregnancy: effects of insulin-like growth factor on progesterone secretion. AB - The effects of insulin-like growth factor-1 (IGF-1) and cAMP on progesterone (P) secretion by CL of streptozotocin-induced-diabetic pregnant ewes were compared with the effects on normal pregnant animals. Two types of CL were identified in the ovaries removed on Days 126.6 +/- 2 of pregnancy. They were either large, reddish in color, and vascular (type A) or small and pale yellow (type B). Both types were found in diabetic and normal sheep. Each CL was divided in two and perfused in parallel for 14 h in an in vitro microdialysis-perifusion system. One half was used to evaluate basal P secretion and the effect of cAMP. The effect of IGF-1 and cAMP infusion was studied in the other half. During microdialysis, fractions were collected every 15 min, and P was determined by RIA. IGF-1 stimulated secretion of P in the large type A, normal and diabetic sheep CL in discrete pulses. The smaller CL (type B) from normal sheep produced comparatively higher levels of P in discrete pulses in the presence of IGF-1. However, the small CL from diabetic sheep showed no response to IGF-1 or cAMP, and P secretion was lower. Thus, it is probable that the large CL may be the "active" CL producing P and that IGF-1 stimulates pulsatile P secretion in such CL from both normal and diabetic pregnant sheep. PMID- 7888510 TI - Status of glutathione during oxidant-induced oxidative stress in the preimplantation mouse embryo. AB - Experiments were conducted to elucidate the status of glutathione present in the oxidized (GSSG), reduced (GSH), and protein-mixed disulfide (GSSprotein) forms in preimplantation mouse embryos during development and after treatment with tertiary-butyl hydroperoxide (tBH) to cause oxidative stress. Glutathione was measured at picomolar levels by fluorimetric HPLC after derivatization of extracted embryonic samples with dansyl chloride. GSH content decreased approximately 10-fold from that in the unfertilized oocyte to 0.12 pmol/blastocyst, representing an estimated change in concentration from 7 to 0.7 mM. GSH levels were lower in embryos cultured in vitro than in embryos that developed in vivo. Addition of GSH to the culture medium improved in vitro development of mouse embryos, but surprisingly the addition of glutathione monoethyl ester did not. Addition of low levels of the oxidant tBH (13.2 microM) to culture medium decreased the percentage of two-cell and blastocyst stage embryos that exhibited further development. After 15-min exposure to 13.2 microM tBH, GSH levels were markedly decreased in the two-cell stage embryo (75%), but only slightly decreased (25%) in the blastocyst. The loss of GSH was accounted for by increases in GSSG and GSSprotein, indicating that the embryo was undergoing oxidative stress. These data indicate that preimplantation embryos are very sensitive to conditions that can cause oxidative stress and show also that their glutathione status changes dramatically during development. PMID- 7888511 TI - Photoperiod regulates testis cell apoptosis in Djungarian hamsters. AB - Reproductive activity in the Djungarian hamster is controlled by seasonal variations in day length. Exposure to long days stimulates testis development, while exposure to short days induces testis regression. We recently found that testis regression after gonadotropin deprivation in rats is associated with increases in apoptosis. Here we sought to determine whether or not apoptosis is associated with the testis regression and/or recrudescence that occurs naturally in seasonally breeding mammals. Newborn male hamsters were maintained on long days (16L:8D) until 3 wk of age before being transferred to short days (8L:16D). Following decreases in serum FSH within 3 days of exposure to short days, testis weight decreased by 52% at Day 10, reaching a 70% decrease after 21 days. Analysis of testis cell DNA fragmentation showed a 4.9-fold increase of low molecular-weight DNA as early as 5 days after transfer to short days; this was followed by a time-dependent decrease. The observed increases in testis cell apoptosis were correlated with decreases in serum testosterone, but decreases in Leydig cell LH receptor content were delayed. In a second study, 6-wk-old hamsters with regressed testes due to a 3-wk exposure to short days were transferred back to long days. After increases in serum FSH within 3 days of photostimulation, a 2-fold elevation in testis weight was found at Day 5. The increase in testis weight was associated with a 65% decrease of testis apoptosis within 5 days of photostimulation. Also, increases in serum testosterone and LH receptor content were observed after 5 and 10 days of exposure to long days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888512 TI - Identification of a functional cyclic adenosine 3',5'-monophosphate response element in the 5'-flanking region of the gene for transition protein 1 (TP1), a basic chromosomal protein of mammalian spermatids. AB - Transition protein 1 (TP1) is a small basic chromosomal protein that appears in mammalian spermatids during the period of chromatin condensation. The gene for TP1 from several species contains an apparent cAMP response element (CRE) in the immediate 5'-flanking region. The recent identification of high expression of the novel CRE-activating protein (CREM tau) in advanced testicular germ cells provided a stimulus to ask whether or not the TP1 CRE is functional. To this end we show both by gel retardation and by footprint assays that TP1 CRE forms specific bound complexes with proteins in whole testis nuclear extracts and that these complexes involve CREM as evidenced by recognition by a specific antibody. In addition, the TP1 CRE forms specific bound complexes with bacterially expressed CREM tau. Finally, the TPI CRE conveys protein kinase A-dependent induction to a linked chloramphenicol acetyl transferase gene when transfected into JEG-3 cells. Accordingly, TP1 is a good candidate for a testis-specific gene subject to CREM tau regulation. PMID- 7888513 TI - [Inhalation anesthesia and intravenous anesthesia from the medical and economic viewpoint]. AB - The unique pharmacokinetic properties of propofol gave rise to a widespread use of the technique of total intravenous anaesthesia. These properties of propofol are reviewed and compared to those of barbiturates and benzodiazepines. Based on this comparison and with respect to their respective intra- and postoperative effects, a cost-benefit analysis of both inhalational- and intravenous anaesthesia is presented. The choice of an anaesthetic technique must not only be made with regard to medical implications; economical aspects have also to be taken into account without challenge to the quality of care. A consequent use of low-flow techniques and a market oriented purchase of drugs and disposables may allow cost savings in anesthesia. PMID- 7888514 TI - [Lithotomy position: respiratory resistance with thiopental and propofol anesthesia]. AB - OBJECTIVE: To study airway resistance changes induced by placement in lithotomy position under thiopentone and propofol anaesthesia. DESIGN: Prospective, randomised study. SETTING: OR of a university hospital. PATIENTS: Consecutive sample of 36 patients without bronchopulmonary disease (ASA 1-2; 18-78 yr.; 45 100 kg) scheduled for elective surgery in lithotomy position under general (mask) anaesthesia; oral premedication with 0.3 mg.kg-1 dipotassium chloroazeptate on the evening before and in the morning of surgery. INTERVENTIONS: Injection of either 4-6 mg.kg-1 thiopentone or 2-2.5 mg.kg-1 propofol into a fast running peripheral infusion until loss of eyelash reflex. Placement of an oropharyngeal airway and assisted ventilation via anatomic mask until recovery of spontaneous respiration. Oscilloresistometric determination (Siregnost FD 5; Siemens AG, Erlangen) of airway impedance (ROS) before and after placement in lithotomy position. RESULTS: Before positioning ROS was 3.5 +/- 1.3 mbar.l-1.s-1 and 3.7 +/ 1.1 mbar.l-1.s-1 in the propofol and thiopentone group respectively. After positioning ROS was unchanged in the propofol group (3.8 +/- 1.8 mbar.l-1.s-1) and increased to 4.5 +/- 1.5 mbar.l-1.s-1 (p < 0.05) in the thiopentone group. CONCLUSION: Lithotomy positioning induces an increase in airway impedance under thiopentone but not under propofol anaesthesia. PMID- 7888515 TI - [Nausea and vomiting after gynecologic laparoscopies]. AB - OBJECTIVE: To investigate the occurrence of postoperative nausea and vomiting (PONV) in relation to the menstrual cycle in patients anaesthetised with isoflurane and propofol. METHODS: 150 patients were randomly allocated to two groups (n = 75). All patients received antiemetic treatment with 20 micrograms/kg droperidol i.v. before induction of anaesthesia. In the isoflurane group, patients were anaesthetised with thiopental, fentanyl, vecuronium, and isoflurane; in the propofol group, with propofol, fentanyl, and vecuronium. Patients were ventilated with nitrous oxide/oxygen in both groups. RESULTS: Under isoflurane-based anaesthesia PONV occurred in 22 (29%) patients, under propofol based anaesthesia in 4 (5%) patients (p < 0.05). 41 study participants underwent laparoscopy during the first 8 days of the menstrual cycle. 12 (29%) of these patients developed PONV (p < 0.05 vs second and third phase of the menstrual cycle). 10 of these 12 study participants were in the isoflurane group. Postoperative shivering occurred in 38 (51%) patients anaesthetised with isoflurane and in 12 (16%) patients of the propofol group (p < 0.05). CONCLUSIONS: The incidence of PONV is significantly higher when patients undergo laparoscopy during the first 8 days of the menstrual cycle. When compared to isoflurane, propofol results in a significantly lower incidence of PONV and postoperative shivering and a lower occurrence of postoperative pain. PMID- 7888516 TI - [Treatment of postoperative shivering with nalbuphine]. AB - OBJECTIVE: Postoperative shivering is common and has potentially adverse side effects in high-risk patients. Meperidine, which binds to both mu- and kappa opioid receptors, is reported to be more effective in treating shivering than morphine or fentanyl. Recent data indicate that much of meperidine's special antishivering effect may be mediated by its kappa-opioid receptor activity. Nalbuphine, an opioid agonist/antagonist also has a potent affinity for kappa receptors. The aim of this study was to evaluate the antishivering effect of nalbuphine in comparison to meperidine. METHODS: 100 ASA physical status I-II patients shivering after elective surgery were included in the study. General anaesthesia was performed with thiopentone, low-dose fentanyl and enflurane in N2O/O2. After arrival in the recovery room patients shivering within 5 min received either meperidine 25 mg or nalbupine 10 mg in a double-blind, randomised manner. The duration and severity of shivering, heart rate, respiratory rate, blood pressure, end-tidal CO2 concentration, O2-saturation and awareness were documented until 20 min after injection. Patients in need of a second injection were excluded from the study. RESULTS: Demographic variables, duration of operation and temperature decreases were not significantly different between treatment groups. The suppression of shivering was achieved within 4.0 +/- 3.5 or 4.6 +/- 4.1 min following the injection of meperidine or nalbuphine, respectively (p = NS). Vital signs and postoperative vigilance showed no significant differences. No adverse side effects were observed. DISCUSSION: The data indicated that nalbuphine suppressed postoperative shivering as effectively and timely as meperidine in equianalgesic doses. The observation is consistent with the hypothesis that stimulation of kappa-opioid receptors is a likely explanation for much of meperidine's antishivering action. PMID- 7888517 TI - [Allergic and pseudo-allergic reactions in anesthesia. I: Pathogenesis, risk factors, substances]. AB - In this article we present a survey on the pathogenesis of allergic or pseudoallergic reactions in anaesthesia, the risk factors and the responsible substances. The incidence of anaphylactoid reactions is between 1:3500 and 1:20,000 anaesthetic cases. The estimated mortality rate amounts to 3-6%. Neuromuscular blocking drugs account for most of the cases of significant anaphylactoid reactions (59-70%). However, the incidence of latex-related reactions in increasing. Risk factors for anaphylaxis are a history of IgE mediated drug allergy, repeated anaesthesias, atopy, hyperventilation tetany, and the use of neuromuscular blocking drugs in females. Risk factors for pseudoallergic reactions are emotional stress, atopic predisposition, increased sensitivity for histamin, hyperventilation tetany and female gender. PMID- 7888518 TI - [Hemo- and cardiodynamic effect of nifedipine in halothane or isoflurane anesthesia. An animal experiment study]. AB - OBJECTIVE: The present experimental study on 16 acutely instrumented dogs was designed to determine the haemo- and cardiodynamic changes after an intravenous infusion of nifedipine during halothane or isoflurane anaesthesia. METHODS: General anaesthesia was induced with ketamine (10 mg/kg) and fentanyl (0.02 mg/kg) and maintained with fentanyl (0.3 micrograms/kg/min), 3:1 N2O/O2 inhalation mixture, and pancuronium (300 micrograms/kg/h). A left thoracotomy was performed and a needle force probe was placed in the left ventricular wall to measure myocardial force of contraction. A Widney gauge was placed around the left ventricle to measure left ventricular circumference changes. The animals were also monitored with left ventricular tip manometers, pulmonary arterial thermodilution catheters, and femoral arterial and venous catheters. Three hours after instrumentation baseline haemodynamic measurements were performed and repeated 30 min after either halothane 0.8 vol.% (n = 8) or isoflurane 1.5 vol.% (n = 8). Then nifedipine (10 micrograms/kg i.v.) was administered and haemodynamic measurements were repeated. RESULTS: Both volatile anaesthetic agents caused a decrease in MAP, CO, LVP, LVFS, and dP/dtmax. Heart rate, CVP, PAOP, and the diastolic diameter of the heart did not change with halothane and isoflurane. Isoflurane led to a decrease of SVR that was not seen with the administration of halothane. Nifedipine during halothane anaesthesia caused a further decrease in MAP, SVR, LVP, dP/dtmax, and LVFS compared to the already reduced values with halothane alone. However, SV did not decrease any further. If nifedipine was added to isoflurane a further decrease in CO and SV was observed despite a constant SVR. CONCLUSION: Halothane, isoflurane and nifedipine are cardiac depressant drugs. Isoflurane induces vasodilation and appears to be less cardiodepressant than halothane in the clinical situation. However, if nifedipine is added, the vasodilation caused by nifedipine offsets its own negative inotropic effect and in parts the cardiac depression of halothane. Combined with isoflurane the vasodilatory effect of nifedipine is insignificant and the negative inotropic effects of both drugs are additive resulting in a profound decrease in SV and CO. PMID- 7888520 TI - [Medical standards in legal procedures]. PMID- 7888519 TI - [John Snow (1813-1858): experimental studies on rebreathing of anesthetic gases in exhaled air]. AB - As early as in 1850 (only 4 years after the first clinical performance of ether anaesthesia by W. T. G. Morton on 16 October 1846) John Snow recognised that ether and chloroform were exhaled unchanged with the expired air. To reuse these unchanged vapours in the following inspiration and thereby prolonging the narcotic effect of a given amount of anaesthetic vapour, he converted his ether inhaler into a To-and-Fro Rebreathing System: The apparatus was equipped with a facemask without an expiratory valve and a large reservoir bag containing pure oxygen; an aqueous solution of caustic potash was used as CO2 absorbent. In several experiments, performed on himself, Snow succeeded to demonstrate that rebreathing of the exhaled vapours was possible following carbon dioxide absorption, and that it resulted in a pronounced prolongation of the narcotic effects of the volatile anaesthetics. Furthermore, Snow performed experiments on animals using a closed system for evaluating the carbon dioxide production during anaesthesia. It is all the more worthwhile to introduce Snow's publications on these topics, as, despite their extraordinary theoretical and practical significance, they remained nearly unnoticed. Even in the fundamental articles by D. Jackson and R. Waters, both being the respected protagonists of the rebreathing technique in anaesthesia, the Snow papers remained uncited. PMID- 7888521 TI - [What is the origin of medical standards (regulations regarding medical competence)?]. PMID- 7888522 TI - [Limits of methodological freedom in anesthesia: from the viewpoint of the legal expert]. PMID- 7888523 TI - [Limits of methodological freedom in anesthesia: from the viewpoint of the medical expert]. PMID- 7888524 TI - [Status and function of the anesthesiologic expert witness in the malpractice process]. PMID- 7888525 TI - Anthrax. PMID- 7888526 TI - Variability of tuberculosis trends in a time of resurgence. PMID- 7888527 TI - Photo quiz. Sweet's syndrome. PMID- 7888528 TI - Pott's disease caused by Mycobacterium xenopi: case report and review. AB - We report a case of Mycobacterium xenopi infection of the spine in a 70-year-old woman. The findings of our case and of five other published reports of bone or joint infection with M. xenopi illustrate the problems with diagnosis and management of infection with this organism. Detection of M. xenopi in clinical specimens may require prolonged incubation at 37 degrees C or incubation at higher temperatures. Furthermore, M. xenopi may be misidentified as Mycobacterium avium-Mycobacterium intracellulare complex. For these reasons, human infection due to M. xenopi may be underrecognized. The optimal therapy for human infection with M. xenopi is unknown. PMID- 7888529 TI - Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City. AB - Cryptococcal infections are not reportable illnesses, and there have been limited attempts to estimate their incidence or prevalence. This study estimates the prevalence of cryptococcal disease in New York City in 1991 among human immunodeficiency virus (HIV)-infected patients who were at risk. Numerator data were generated by surveying all hospitals in New York City to determine the number of patients with cultures positive for Cryptococcus neoformans as well as the number of patients with positive cryptococcal latex agglutination tests in 1991; 517 culture-positive patients were identified, and 1,277 patients were estimated to have a positive cryptococcal latex antigen test. Of these cases, 96% were estimated to be related to infection with HIV. Denominator data were generated via an active surveillance program of the New York City Department of Health. The annual prevalence of cryptococcosis among HIV-infected patients at risk in New York City is estimated to be 6.1%-8.5%. PMID- 7888530 TI - Phase 2 efficacy trial of an oral 8-aminoquinoline (WR6026) for treatment of visceral leishmaniasis. AB - The efficacy of an oral 8-aminoquinoline (8-[[6-(diethylamino)hexyl]amino]-6 methoxy-4-methylquinoline) (WR6026) in the treatment of 16 patients with kala azar was evaluated. The first 8 patients received therapy for 2 weeks at a dosage of 0.75-1.00 mg/(kg.d); 1 patient was cured, and in regard to the other 7, a 1 logarithm decrease in the number of splenic parasites and clinical improvement were noted. The next 8 patients received therapy for 4 weeks at the same daily dosage (1 mg/[kg.d]); 4 were cured, and for the other 4, 1- to 2-log decreases in the number of parasites and clinical improvement (in regard to weight, liver and spleen size, hemoglobin level, and leukocyte count) were noted. The therapy was associated with minimal toxicity; adverse effects included gastrointestinal distress, headache, and methemoglobinemia. The fact that one-half of the patients were cured indicates that future trials with longer regimens and higher dosages are warranted and should include patients for whom existing treatment methods have failed. PMID- 7888531 TI - Biological false-positive syphilis test results for women infected with human immunodeficiency virus. AB - Regardless of the nontreponemal test used for the screening and diagnosis of syphilis, biological false-positive results (BFPs) are documented in 1%-2% of all cases. An association between BFPs and human immunodeficiency virus (HIV) infection in men has been suggested. We conducted a cohort study to determine whether a similar association between HIV seropositivity and BFPs exists for women. Among 156 HIV-seropositive women, 9 (5.8%) had a BFP for syphilis. Among 633 HIV-seronegative women, only 1 (0.2%) had a BFP. When the 25 HIV-seropositive patients and 55 HIV-seronegative patients with reactive rapid plasma reagin tests and microhemagglutination assays for antibodies to Treponema pallidum were excluded from the calculations, 6.9% and 0.2% of HIV-seropositive and HIV seronegative women, respectively, had BFPs (P < .001; odds ratio, 39.45; 95% confidence interval, 6.4-879.0). An association was found between injection drug use and BFPs for the population of HIV-infected women but did not entirely account for the differences between this group and the HIV-seronegative group. PMID- 7888532 TI - Adenovirus parotitis in patients with AIDS. AB - Adenoviruses are well documented as opportunistic pathogens in patients with immunocompromising conditions, including human immunodeficiency virus (HIV) infection. We recently diagnosed adenovirus infection of the parotid gland in two patients with AIDS. Viral cultures and electron microscopic examinations of parotid tissue were positive in both cases. Adenovirus infection should be considered in the differential diagnosis of parotid swelling in HIV-infected patients. PMID- 7888533 TI - Fungal infection of ventriculoperitoneal shunts in children. AB - Infection is still the most common complication of shunt procedures in children. However, fungal infection is still considered to be rare. We found that fungi accounted for 17% of shunt infections (8 of 48) in a retrospective study. All of the patients were premature babies and had received a ventriculoperitoneal shunt because of hydrocephalus. The clinical manifestations were subtle and insidious. The time of onset of infection ranged from 1 month to 1 year after the insertion of the shunt. Examination of the cerebrospinal fluid of infected patients showed mild pleocytosis with an elevated protein concentration. Candida species (including Candida albicans, Candida parapsilosis, and Candida tropicalis) or Torulopsis glabrata were isolated. In all but one case, shunts were removed and systemic therapy with amphotericin B was administered. Amphotericin B was given intrathecally to two patients, who did not respond to systemic therapy. Treatment with fluconazole failed for one patient. We suggest performing fungal cultures in cases of shunt infection, especially those involving premature infants. Extraventricular drainage, systemic therapy with amphotericin B, and insertion of a new shunt remain the principal components of the treatment regimen for fungal shunt infections in children. PMID- 7888534 TI - Native valve endocarditis due to Corynebacterium striatum: case report and review. AB - We report the first known case of native valve endocarditis due to Corynebacterium striatum and review 51 previously reported cases of native valve endocarditis due to non-diphtheriae corynebacteria. Of the 52 patients with corynebacterial endocarditis, 11 (21%) had no predisposing conditions and 27 (52%) had structural heart disease; endocarditis in the remaining 14 patients (27%) was associated with noncardiac predisposing factors including injection drug use, chronic hemodialysis, vasculitis, alcoholism, liver transplantation and hemodialysis, a peritoneovenous shunt, and prior aspiration of a noninfected bursa. The mortality rate associated with corynebacterial endocarditis was 31%. The majority of corynebacteria in this series were sensitive to penicillin, erythromycin, gentamicin, and vancomycin. Non-diphtheriae corynebacteria are capable of producing acute valvular damage, even in patients without conditions that are predisposing for endocarditis. The occurrence of bacteremia due to non diphtheriae corynebacteria in the appropriate clinical setting should alert physicians to the possible diagnosis of endocarditis. Empirical antibiotic therapy with vancomycin, with or without an aminoglycoside, should be initiated pending antibiotic susceptibility testing. PMID- 7888535 TI - Mycoplasma hominis septic arthritis: two case reports and review. AB - Mycoplasma hominis is normally a commensal of humans. When the organism is pathogenic, it primarily causes disease in the genitourinary tract. Septic arthritis caused by M. hominis is a rare condition that occurs chiefly in the postpartum period, in immunosuppressed hosts, or in patients who have recently undergone urinary tract manipulation. Arthritis caused by M. hominis is clinically indistinguishable from septic arthritis caused by other bacteria. Diagnosis is often delayed because infection with this organism is not suspected or because it grows slowly, if at all, in routine culture media. Appropriate therapy often leads to a good outcome, although relapses and resistance have been reported. PMID- 7888536 TI - Expanded distribution of an investigational drug in parallel with ongoing controlled clinical trials: the didanosine model. AB - The purpose of the didanosine Expanded Access Program was to provide a needed antiretroviral agent to individuals who were unable to tolerate other therapy for human immunodeficiency virus infection or in whom such therapy was failing. The logistics of establishing this program are described, and the results of on-site auditing that confirmed the validity of the data obtained through this program are presented. PMID- 7888537 TI - Rates and risk factors for adverse events associated with didanosine in the expanded access program. AB - The didanosine Expanded Access Program was the largest AIDS treatment program to prospectively evaluate the safety of an antiretroviral agent among patients with advanced human immunodeficiency virus (HIV) disease in whom therapy with zidovudine was failing. A total of 21,198 patients who had infections refractory to zidovudine or who were intolerant of the drug received didanosine as a buffered powder for oral solution (sachet), with total daily doses of 6.6-10 mg/kg; the median CD4 lymphocyte count was 0.04 x 10(9)/L for this population. At the currently recommended dose (6.6-8.29 mg/[kg.d]), 6-month estimated rates of pancreatitis ranged from 1.2% for patients with AIDS-related complex (ARC) and CD4 lymphocyte counts of > or = 0.1 x 10(9)/L to 6.7% for patients with AIDS and CD4 lymphocyte counts of < 0.05 x 10(9)/L. Laboratory toxicities of World Health Organization grades 3 and 4 developed in fewer than 4% of patients entering the study with normal baseline values; the sole exception was leukopenia, which was documented in 8% of these patients. The results of this program demonstrated that patients with CD4 lymphocyte counts of < 0.10 x 10(9)/L or with a diagnosis of AIDS (defined by the 1987 classification system of the Centers for Disease Control and Prevention) were less tolerant of didanosine and significantly more likely to develop adverse clinical reactions and myelosuppression than other patients. PMID- 7888538 TI - Serological analysis of pulmonary and extrapulmonary tuberculosis with enzyme linked immunosorbent assays for anti-A60 immunoglobulins. AB - IgA, IgG, and IgM antibodies to mycobacterial antigen A60 were measured by ELISA in blood, pleural fluid, and cerebrospinal fluid from 560 patients with pulmonary and/or extrapulmonary tuberculosis who were being treated at hospitals in northern China and from 734 uninfected controls. Among 529 healthy persons (most of whom had been vaccinated with bacille Calmette-Guerin [BCG] and 287 of whom were tuberculin-positive), the rate of false-positive results was negligible; this observation ruled out interference of remote BCG vaccination with A60 assays at the chosen cutoff level. Rates of positivity for IgM and IgG, respectively, were 80% and 36% among patients with active primary pulmonary tuberculosis, 31% and 88.5% among patients with active postprimary pulmonary tuberculosis, 0 and 41% among patients with inactive pulmonary tuberculosis, and 30%-61% and 69%-86% among patients with extrapulmonary tuberculosis. Paired samples of blood and pleural fluid from patients with pleurisy contained IgA antibody to A60 at equal titers; in contrast, most patients with tuberculous meningitis (100% of whom had a positive ELISA result) had higher levels of IgG antibody to A60 in cerebrospinal fluid than in blood--proof of intrathecal synthesis. PMID- 7888539 TI - Paradoxical enlargement or development of intracranial tuberculomas during therapy: case report and review. AB - Intracranial tuberculomas can sometimes develop or increase in size despite administration of appropriate therapy. We report the case of a child whose intracranial tuberculomas paradoxically enlarged while therapy was being administered, and we review 23 other cases in which tuberculomas increased in size or number and 17 cases in which tuberculomas appeared during therapy. These phenomena generally occurred within 3 months of the start of therapy. All but four patients had neurological deterioration that prompted obtaining a repeated computed tomographic scan. One patient died, about one-fourth of patients had residual neurological symptoms, and less than one-third of the patients required surgical intervention. Most patients received a 12-18 month course of antituberculous therapy. Adjunctive therapy with steroids appears to diminish neurological symptoms and may improve outcome. Paradoxical enlargement or development of tuberculomas usually does not represent failure of antituberculous therapy; the most likely explanation for these phenomena is an interaction between the host's immune response and the direct effects of mycobacterial products. PMID- 7888540 TI - Tuberculin reactions among attendees at a methadone clinic: relation to infection with the human immunodeficiency virus. AB - We tested 403 clients at an inner-city methadone clinic to determine the rate of positive tuberculin test reactions and to determine how this rate was influenced by race, gender, and infection with the human immunodeficiency virus (HIV). In addition to skin testing, an experimental urine test for antibody to HIV was offered; 73% of the clients provided urine specimens. Positive urine test results were confirmed by serum antibody testing. Of the subjects who returned for follow up, 33.9% had indurations > or = 10 mm; 49.7% of these subjects were Black, 30% were Hispanic, and 18% were White. Antibodies to HIV were present in 12.5% of urine specimens. Tuberculin reactions of > or = 5 mm were observed for 32.7% of HIV-positive subjects and 48.4% of HIV-negative subjects. Screening of urine for antibodies to HIV proved to be simple, specific, and well accepted by the subjects. Providing prophylaxis for tuberculosis should be a high priority in populations with rates of tuberculin reactions and HIV infection that are comparable to those for clients of our methadone clinic. PMID- 7888541 TI - Hantavirus pulmonary syndrome in California: report of two cases and investigation. AB - We report two cases of hantavirus pulmonary syndrome that were probably acquired in California. Genetic analysis of tissue specimens from one of the patients revealed that the virus isolated is a variant of the strain (Sin Nombre virus) identified in the outbreak of hantavirus pulmonary syndrome that occurred in the Four Corners region of the southwestern United States in 1993. In addition to presenting the clinical features of the two cases, we discuss the possible risk factors for infection. PMID- 7888542 TI - A 45-year perspective on the streptococcus and rheumatic fever: the Edward H. Kass Lecture in infectious disease history. AB - Rheumatic fever has been considered a major problem among civilians in the United States and elsewhere for 100 years but was not recognized as a concern among the U.S. military until World War II. At that time the only available control measure was antimicrobial prophylaxis of recurrent rheumatic fever. Subsequent studies, conducted primarily by the Streptococcal Diseases Laboratory of the Armed Forces Epidemiological Board, demonstrated that rheumatic fever could be prevented by the treatment of patients with streptococcal pharyngitis and by the administration of penicillin for the prophylaxis of streptococcal infections in large groups. With the use of available preventive measures, rheumatic fever virtually disappeared by the 1970s. In 1985, however, rheumatic fever and severe streptococcal infections reappeared, first in the Rocky Mountain area. It is speculated that this reappearance was due to special strains of group A streptococci and--in severe cases--the production of pyrogenic exotoxins. At present, cases continue to occur but not at the level seen in the late 1980s. PMID- 7888543 TI - Efficient detection and long-term persistence of the carriage of methicillin resistant Staphylococcus aureus. AB - The natural history of the carriage of methicillin-resistant Staphylococcus aureus (MRSA) was examined in a 9-year retrospective cohort study of 102 known carriers. The populations studied consisted of patients admitted to a university hospital from 1989 through 1991; a review extending back to January 1983 was conducted. The focuses of the study included the duration of carriage among patients who were known to have carried MRSA previously and who were readmitted to the hospital (36 patients) and the optimal anatomic site for screening (66 patients). Cultures of the nares (sensitivity, 93%; negative predictive value, 95%) were considerably more valuable for the detection of MRSA colonization than were cultures of cutaneous sites of the axilla, groin, and perineum (sensitivity, < or = 39%; negative predictive value, < or = 69%). The estimated half-life of MRSA colonization in this special population of patients was approximately 40 months. Restriction enzyme analysis of plasmid types of paired isolates from the 12 patients with MRSA carriage persisting for > 12 months revealed five instances (42%) in which both isolates were of the same type. In summary, our results indicate that the majority of readmitted carriers harbor MRSA for > 3 years and that, in this population, culture of the anterior nares alone (with culture of wound or sputum, when present) is a valid and efficient method for the detection of persistent MRSA carriage. PMID- 7888544 TI - Recurrent infection due to Legionella pneumophila in a patient with AIDS. AB - We report a patient with AIDS who presented with community-acquired cavitary Legionella pneumophila pneumonia. The patient recovered after an extended course of treatment with macrolide antibiotics. He returned to the hospital 4 months later with a febrile illness. Chest radiograms appeared normal. Cultures of blood yielded L. pneumophila. The isolate from blood was indistinguishable from the isolate from sputum taken during the first infection, as shown by restriction endonuclease analysis and pulsed-field gel electrophoresis. These data suggest that the second infection represented reactivation of a persistent focus of infection that was not apparent when the patient had pneumonia. PMID- 7888545 TI - Cerebral mucormycosis associated with intravenous drug use: three case reports and review. AB - We describe three cases of cerebral mucormycosis in intravenous drug users and review 22 previously reported cases. Involvement of the basal ganglia was demonstrated in all but two cases. Seven of the 10 patients tested for antibodies to the human immunodeficiency virus (HIV) were seronegative. Eight of the 25 patients survived and were discharged from the hospital; for 7 of 10 patients, cultures of brain lesions yielded Rhizopus arrhizus. The radiographic findings varied, and in most cases, no or minimal contrast enhancement was seen in the initial computed tomography scans. Although uncommon, the diagnosis of cerebral mucormycosis should be considered when basal ganglia lesions are present in an intravenous drug user, regardless of previous exposure to HIV. PMID- 7888546 TI - Staphylococcus epidermidis meningitis and an intraspinal abscess associated with a midthoracic dermal sinus tract. AB - Congenital neuroectodermal defects are associated with meningitis that is unresponsive to conventional antibiotic therapy, recurrent bacterial meningitis, or meningitis due to an organism that is not usually the cause of this disease. Midthoracic dermoid and epidermoid cysts occur rarely and are easily overlooked. We report the case of a 13-month-old boy with meningitis that was unresponsive to antimicrobial therapy. We subsequently identified an intraspinal abscess, an infection due to Staphylococcus epidermidis, and a midthoracic dermoid cyst. We emphasize the need for clinicians to have a high index of suspicion and to make a careful physical examination when antibiotic treatment fails in patients with meningitis. We also provide a detailed anatomy of a midthoracic dermoid cyst and illustrate the usefulness of magnetic resonance imaging in preoperative diagnosis of congenital neuroectodermal defects. PMID- 7888547 TI - Plasma levels of tumor necrosis factor alpha in patients with Mediterranean spotted fever: clinical and analytical correlations. AB - Twenty consecutive patients with serologically confirmed Mediterranean spotted fever were analyzed for determination of plasma levels of tumor necrosis factor alpha (TNF-alpha) by means of an ELISA. Increased levels of TNF-alpha in plasma were found during the acute phase of the disease (52.3 +/- 49.8 pg/mL) compared to levels in the convalescent phase (9.0 +/- 9.3 pg/mL; P < .001) or in healthy controls (6.5 +/- 3.2 pg/mL; P < .001). Plasma TNF-alpha levels were significantly higher in patients with severe Mediterranean spotted fever. Levels of TNF-alpha correlated significantly with serum levels of C-reactive protein and triglycerides and inversely with serum levels of sodium. PMID- 7888548 TI - Immigration of Ethiopians with typhoid fever to Israel: apparent lack of influence on the local population. AB - The epidemiology of typhoid fever in Western countries may be affected by immigration from developing countries. We studied the immigration of Ethiopian Jews to Israel to find the effects of an influx of many individuals infected with typhoid into an area with a low incidence of the disease. Typhoid fever affected 204 Israelis and 121 (1.1%) of 10,654 Ethiopian immigrants during the period of 1984-1985. Of those Ethiopian cases, 107 occurred during a 3-month period. During the 5 months following that 3-month period, there was no increase in the number of cases of typhoid among Israelis. Although after that time there was a local waterborne outbreak of typhoid that affected 83 Israelis, no Ethiopians resided in the area where the outbreak occurred; therefore, we concluded that these 83 cases of typhoid fever were not related to the immigration of Ethiopians into Israel. In fact, if those 83 cases were excluded from the statistical analysis, there was no increase in the occurrence of typhoid during the 2-year period studied. Therefore, the immigration of many people with typhoid into an area of low incidence does not necessarily confer a risk of infection to the local population. PMID- 7888549 TI - Reinfection with Legionella pneumophila documented by pulsed-field gel electrophoresis. AB - A 50-year-old man with chronic lymphocytic leukemia experienced two episodes of community-acquired legionnaires' disease. For determining whether this was the result of relapse or reinfection, Legionella pneumophila strains, cultured from sputum specimens and his home water supply, were characterized by pulsed-field gel electrophoresis. Analysis of the restriction patterns and the clinical data indicated that the second disease period was most likely the result of reinfection. We conclude that after diagnosis of community-acquired legionnaires' disease in an immunocompromised patient, culturing of the domestic water supplies for L. pneumophila should be considered; if such cultures are positive, adequate measures to prevent reexposure have to be taken. PMID- 7888550 TI - Intravenous streptomycin: a useful route of administration. AB - Streptomycin is an aminoglycoside antibiotic that is indicated for the treatment of tuberculous and nontuberculous infections. Intramuscular injection is the recommended route of administration. There are few reports on intravenous administration of streptomycin. We describe the use of intravenous streptomycin to treat endocarditis due to a strain of Enterococcus faecalis with high-level resistance to gentamicin. Physicians should consider the intravenous route as an alternate method of administering streptomycin. PMID- 7888551 TI - Mycobacterium genavense infection presenting as a solitary brain mass in a patient with AIDS: case report and review. AB - Patients with AIDS are prone to developing infections with opportunistic pathogens. Recently, a new mycobacterium, Mycobacterium genavense, has been found to cause infection in patients with AIDS. Previously published reports indicate that patients who are infected with this organism present with the same clinical features as do patients with disseminated infection due to organisms of the Mycobacterium avium complex. We describe an unusual case of a patient with AIDS who presented with grand mal seizures and a mass lesion in his brain, which was found to be caused by infection with M. genavense. No evidence of disseminated infection could be found in this patient. We discuss the microbiology of this organism and review the literature on M. genavense infections. Clinicians should be aware of this organism so that efforts at culture and identification will be made. PMID- 7888552 TI - Infection due to Mycobacterium haemophilum identified by whole cell lipid analysis and nucleic acid sequencing. AB - A patient with indolent, non-Hodgkin's lymphoma developed a pretibial soft tissue abscess caused by a fastidious mycobacterium. Because the organism could not be definitively identified by standard microbiologic testing, whole cell fatty acid analysis and 16S rDNA sequencing were performed. These procedures identified the organism as Mycobacterium haemophilum. We review the diagnostic considerations with regard to this pathogen. PMID- 7888553 TI - Levels of tumor necrosis factor alpha, interleukin 6, interleukin 10, and transforming growth factor beta are normal in the serum of the healthy elderly. PMID- 7888554 TI - Primary Sjogren's syndrome and antibodies to human herpesvirus type 6. PMID- 7888555 TI - Pseudomembranous colitis associated with Hirschsprung's disease. PMID- 7888556 TI - Metronidazole therapy for visceral leishmaniasis. PMID- 7888557 TI - Subacute pneumococcal pericarditis in a patient who did not develop tamponade. PMID- 7888558 TI - Diagnosis of legionella sepsis by examination of a peripheral blood smear. PMID- 7888559 TI - Varicella immunity in women infected with the human immunodeficiency virus. PMID- 7888560 TI - Mobiluncus curtisii bacteremia following septic abortion. PMID- 7888561 TI - Myelitis due to Toxoplasma gondii in a patient with AIDS. PMID- 7888562 TI - Pericarditis associated with Legionnaires' disease in a bone marrow transplant recipient. PMID- 7888563 TI - Leukopenia in patients with cirrhosis who were treated with beta-lactam antibiotics. PMID- 7888564 TI - Clarithromycin-induced thrombocytopenic purpura. PMID- 7888565 TI - Sternal wound infection due to Corynebacterium xerosis. PMID- 7888566 TI - Short-term pefloxacin therapy in Madagascan children with shigellosis due to multiresistant organisms. PMID- 7888567 TI - Staphylococcus xylosus isolated from a pancreatic pseudocyst in a patient infected with the human immunodeficiency virus. PMID- 7888568 TI - Fatal postpartum infection with group G streptococcus. PMID- 7888569 TI - Granulomatous submandibular lymphadenitis caused by Salmonella species in a healthy child. PMID- 7888570 TI - Aspergillus tracheobronchitis. PMID- 7888571 TI - Bronchoalveolar carcinoma, lymphoid interstitial pneumonia, and retroviruses. PMID- 7888572 TI - Fluconazole-resistant Candida albicans in an immunocompetent child. PMID- 7888573 TI - Preparation of nanoparticles bearing high density carbohydrate chains using carbohydrate-carrying polymers as emulsifier. AB - A novel method of preparing nanoparticles bearing high density carbohydrate chains on their surface is described. Carbohydrate-bearing nanoparticles of poly(lactic acid) or polystyrene were prepared by the solvent evaporation method using a carbohydrate-carrying polystyrene derivative which served as both an emulsifier and a surface coating. The diameter of the obtained nanoparticles ranged from 80 to 300 nm depending on the concentration of the polystyrene derivative. As the concentration of the polystyrene derivatives increased the nanoparticle diameter decreased, indicating that the polystyrene derivatives worked as an emulsifier. The obtained particles were specifically aggregated by carbohydrate-specific lectin, showing that the polystyrene derivative was retained on the particle surfaces and expressed carbohydrate residues. The density of carbohydrates on the particle surfaces was determined to be 3-5 molecules per square nanometre. The particles prepared by the present method were stably dispersed and hardly aggregated in aqueous media during storage and centrifugal treatment compared with the post-coated particles that were prepared by adsorbing polystyrene particles with the polystyrene derivative. In vitro study with isolated rat hepatocytes revealed that surface carbohydrate chains were recognized by hepatocytes. PMID- 7888574 TI - Photochemical immobilization of heparin, dermatan sulphate, dextran sulphate and endothelial cell surface heparan sulphate onto cellulose membranes for the preparation of athrombogenic and antithrombogenic polymers. AB - Heparin (HE), dextran sulphate (DX) of molecular weight 40000 and 500000, dermatan sulphate (DS) and endothelial cell surface heparan sulphate (ES-HS) were immobilized covalently onto cellulose membranes (Visking dialysis tubes) using the photochemical heterobifunctional reagent 4-azido-1-fluoro-2-nitrobenzene (AFNB); 120 pmol HE/cm2 and 40 pmol DS/cm2, 3.4 pmol DX 500,000/cm2, 50 pmol DX 40,000/cm2 and 3.6 pmol ES-HS/cm2 were immobilized. The platelet adhesion of the modified membranes was measured in a modified Baumgartner perfusion chamber with citrated human blood at a defined shear rate. Membranes modified with DX 40,000 and DX 500,000 showed 80% and 30% platelet adhesion, respectively, heparinized and DS coated membranes showed 50% and 60% platelet adhesion, respectively, compared with a subendothelial matrix (100% platelet adhesion). ES-HS modified membranes showed no platelet adhesion. PMID- 7888575 TI - Chitosan as a matrix for mammalian cell encapsulation. AB - Cells encapsulated in a semi-permeable polymer membrane display enhanced viability and proliferation when sequestered along with a supportive matrix. In the present study, anionic sodium alginate and cationic chitosan were used as supportive matrices to study their influence on the growth of both anchorage dependent and independent cell types. A phaeochromocytoma-derived cell line, PC12, and two fibroblast cell lines, R208F and R208N.8, were encapsulated in sodium alginate microcapsules, crosslinked chitosan microcapsules and 60:40 acrylonitrile-vinylchloride copolymer (PAN/PVC) macrocapsules containing precipitated chitosan as an internal matrix. Microcapsules were maintained for 2 wk in vitro and macrocapsules were maintained for 4 wk. Both the PC12 and the R208F cells proliferated in the alginate microcapsules. Catecholamine release was detected from PC12 cell-loaded microcapsules. In contrast, the R208N.8 cells were not supported by the alginate and the only viable R208N.8 cells seen in this system protruded from the alginate matrix into the surrounding cationic poly-l lysine lamina. All three cell lines grew poorly in crosslinked chitosan microcapsules yet they exhibited excellent viability when sequestered in PAN/PVC macrocapsules containing an internal matrix of precipitated chitosan. Significant catecholamine levels were detected from macroencapsulated PC12 cells while macroencapsulated R208N.8 cells released nerve growth factor (NGF) as demonstrated by a qualitative bioassay. This study shows that a cationic hydrogel, precipitated chitosan, supports attachment and spreading of fibroblasts when used as a matrix in the lumen of a PAN/PVC macrocapsule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888576 TI - Development of bioabsorbable glass fibres. AB - Calcium-iron phosphate glasses with an iron oxide content ranging from 5 wt.% to 22 wt.% were prepared to investigate the effect of iron oxide on the properties of the glass. It was found that the dissolution rate, the fibre strength and the glass transition temperature were strongly affected by iron oxide. The glass dissolution rate exhibited a 50-fold reduction while the fibre strength doubled when the iron oxide content was increased from 5 wt.% to 22 wt.%. The phosphate glass containing 22 wt.% of iron oxide had a dissolution rate of about 5 micrograms/(cm2 day). The fibres drawn from this glass also exhibited the highest tensile strength over 1000 MPa. A cortical bone plug method was used to assess the biocompatibility of the glasses with the hard and soft tissues. The tissues surrounding the samples showed no inflammation at 9 wk. PMID- 7888577 TI - Bone response to surface modified titanium implants: studies on electropolished implants with different oxide thicknesses and morphology. AB - In a series of experimental studies, bone formation was analysed around systematically modified titanium implants. In the present study, machined, electropolished and anodically oxidized implants were prepared, surface characterized and inserted in the cortical bone of rabbits (7 wks and 12 wks). SEM, scanning Auger electron spectroscopy and atomic force microscopy revealed no differences in surface composition but marked differences in oxide thickness, surface topography and roughness. Light microscopic morphology and morphometry showed that all implants were in contact with bone, and had a large proportion of bone within the threads. The smooth, electropolished implants were surrounded by less bone than the machined implants with similar oxide thickness, (4-5 nm) and the anodically oxidized implants with thicker oxides (21 nm and 180 nm, respectively) after 7 wks. These studies show that a high degree of bone contact and bone formation can be achieved with titanium implants which are modified with respect to oxide thickness and surface topography. However, it appears that a reduction of surface roughness may influence the rate of bone formation in rabbit cortical bone. PMID- 7888579 TI - Modification of layered atelocollagen by ultraviolet irradiation and chemical cross-linking: structure stability and mechanical properties. AB - Physical and chemical modifications of atelocollagen materials have been carried out to improve their physical, chemical and biological properties. We have studied the influence of physical modification using ultraviolet irradiation and of chemical modification using hexamethylene diisocyanate on the physical properties of layered atelocollagen materials. The study evaluated the structural stability of cross-linked materials using swelling experiments. Influence on mechanical properties is also discussed. PMID- 7888578 TI - Stimulatory effect on bone formation exerted by a modified chitosan. AB - A novel modified chitosan carrying covalently linked imidazole groups (average molecular weight 700,000, degree of substitution 0.28, degree of acetylation 0.08) was used to stimulate bone formation in an animal model. Lesions (7 mm diameter) were surgically made in the femoral condyle of sheep and treated with the modified chitosan. Within 40 d after surgery, the neoformed tissue occluded the surgical hole and assumed a trabecular structure in the peripheral area of the lesion, while looking like a mineralization nodule in the central part in association with a fibrous component. In the control, no sign of osteoinduction or reparative process was observed and bone marrow was rich in adipocytes. PMID- 7888580 TI - Sintered porous DP-bioactive glass and hydroxyapatite as bone substitute. AB - There is extensive experimental and surgical experience with the use of bone tissue to fill defects in the skeleton, to bridge non-union sites, and to pack defects in bone created from cyst curettage. DP-bioactive glass with a chemical composition of Na2O 8.4%, SiO2 39.6%, P2O5 12% and CaO 40% has been reported as an alternative bone substitute of high mechanical strength, good biocompatibility. and which has a tight bond with living tissue. The bonding layer between DP-bioactive glass and bone tissue was considered to be formed by dissolution of calcium and phosphate ions from the DP-bioactive glass into the surrounding body fluids. The biological hydroxyapatite was suspected to deposit directly onto the bonding layer. In order to confirm the interaction between the DP-bioactive glass and bone tissue, the developed bioactive glass was implanted into rabbit femur condyle for 2-32 weeks. The histological evaluation of DP bioactive glass as a bone substitute was also investigated in the study. Porous hydroxyapatite bioceramic was used in the control group and the results were compared with those of DP-bioactive glass. The interface between the DP-bioactive glass and bone tissue examined with SEM-EPMA showed that the bioactive glass formed a reaction layer on the surface within 2 weeks after operation and formed a direct bond with natural bone. The elements contained in the bioactive glass apparently interdiffuse with the living bone and biological hydroxyapatite deposited onto the diffusion area, which was proved by EPMA and TEM. After implantation for over 8 weeks, the DP-bioactive glass was gradually biodegraded and absorbed by the living bone. Histological examination using the optical microscope showed that osteocytes grow into the inside of the DP-bioactive glass and the bioactive glass would be expected to be a part of bone. PMID- 7888581 TI - In vivo performance of the polyesterurethane Vascugraft prosthesis implanted as a thoraco-abdominal bypass in dogs: an exploratory study. AB - Among the various prototype vascular prostheses that have been developed over recent years as small vessel substitutes, the Vascugraft polyurethane device produced by Braun-Melsungen AG has a number of attractive features. As well as having high mechanical compliance similar to that of the arterial tree, it has been manufactured from a specially synthesized poly(ester urethane) with improved biostability and its microfibrous structure provides a highly porous wall with open communicating pores. With a view to evaluating the in vivo biofunctionality and biostability of this prosthesis in the dog, 10 mm diameter grafts were implanted as thoraco-abdominal bypasses for prescheduled periods of 1 months and 12 months, and their performance monitored in terms of gross morphology, histology and the measurement of the chemical and physical properties of the explanted and cleaned specimens. Both grafts were patent at retrieval. Each had a smooth and glistening flow surface without organized mural thrombi and showed the development of a thin collagenous internal capsule with the presence of endothelial-like cells. Both grafts were well encapsulated externally and revealed a small distal bend or kink which is frequently observed by any thoraco abdominal bypass in dogs. The fresh explanted prostheses were cleaned by a new enzyme treatment which provided specimens for microscopic, mechanical and thermal analyses, as well as studies of the surface and bulk chemistry. By comparing the results from the explanted and cleaned material with those of the virgin prosthesis, we have observed some deterioration in the integrity of the microfibrous structure, some loss in mechanical performance, marginal changes in molecular weight, and an apparent microphase separation of the hard and soft segment domains at a depth of a few microns. While the biofunctionality of a 10 mm calibre device has been demonstrated, additional in vivo studies are recommended to assess the biofunctionality at different diameters and the biostability over longer periods of implantation. PMID- 7888582 TI - [Profile of the user and tolerance of main contraceptive methods in primary care: hormonal contraceptives, intrauterine devices (IUD) and diaphragm]. AB - OBJECTIVE: To analyse the psycho-social profile of women using hormonal contraceptives (HCC), the intrauterine device (IUD) and the diaphragm; and to evaluate their tolerance to these methods. DESIGN: A prospective observation study. SETTING: The basic unit of family planning at an urban health centre. PATIENTS AND OTHER PARTICIPANTS: 503 patients, for whom contraception was provided between january and may 1992, with a clinical follow-up throughout the year. MEASUREMENTS AND MAIN RESULTS: HCC were administered to 285 women, with an average age of 24.8# 4.38 years. Secondary effects were detected in 14.73% of cases, with good metabolic tolerance. The IUD was provided to 216 users, with an average age of 35.4#-6.39. There was acceptable tolerance, with it being withdrawn in 18 cases, mainly due to spontaneous shedding. There were only two diaphragm users during the study period; and these had good tolerance. CONCLUSIONS: HCC were the contraceptive method chosen most often by younger women. The high tolerance to these methods and easy out-patient control of them make Primary Care, in coordination with other professionals, the ideal level for their prescription. User profiles approach the ideal recommended in the bibliography consulted. PMID- 7888583 TI - [Maintenance therapy with antiulcer drugs: review of 71 cases]. AB - OBJECTIVE: To find the characteristics of our patients being treated with anti ulcer medication and to evaluate whether the prescriptions were correct. DESIGN: A descriptive, crossover study. SETTING: Perpetuo Socorro Health Centre in Huesca. PATIENTS: 71 patients selected through their long-treatment booklets during october-november 1992. MEASUREMENTS AND RESULTS: Using as our data source the clinical records, we evaluated age, gender, toxic habits, associated chronic problems, year and diagnostic method, aptness of the therapy indicated, beginning of long-term treatment, the medication chosen and relapses occurred. A data base dBase III Plus was used, applying a descriptive statistical analysis with the #x2 test, comparison of means and variance analysis. The group's mean age was 61.53 and had a high percentage of associated chronic pathology (81.6%). 69.01% suffered from a duodenal ulcer and 30.99% presented other problems which were susceptible to maintenance treatment with anti-ulcer medication. Overall treatment indication was correct in 87.93% of cases. 83.09% of the patients had long-term therapy, the indication being correct in 74.14%. The proportion of correct treatment was greater in the at-risk group (p < 0.005). The drugs used were ranitidine, famotidine, omeprazole and almagate. CONCLUSIONS: It is important to identify correctly those patients at risk of developing ulcerous pathologies so that the maintenance therapy can be suitably adapted and the best choice of drug be made, with the medical interactions being borne in mind. PMID- 7888585 TI - [Vices of medical language. I. Foreign terms and acronyms]. PMID- 7888584 TI - [Approach to beliefs about health in 2 main health districts]. AB - OBJECTIVE: To investigate whether doctors know users' beliefs about health and to investigate some of these beliefs. DESIGN: A crossover study. SETTING: The Cartuja and Almanjayar Health Centres in Granada. PATIENTS AND OTHER PARTICIPANTS: These were 204 users of the two centres, chosen at random and who attended for on-demand attention for whatever reason. Eleven patients refused the questionnaire. INTERVENTIONS: A 23-question questionnaire was administered during november and december 1993. MEASUREMENTS AND MAIN RESULTS: 64% were women and 36% men. Distribution by age and gender in both centres was similar. Coincidence (defined as 50% of replies totally in agreement and/or in agreement with the item in the questionnaire) between users' beliefs and doctors' opinions of those beliefs was slight (30%). Doctors' opinions concerning their patients' beliefs coincided with the beliefs shown by people with a lower educational level (F = 11.21, p < 0.00001) and over 45 years old (Sp = 0.25, p < 0.001). 70% thought that "illnesses are seen better on the screen"; and 57% that "if analysis and x rays are not done, they don't feel satisfied". CONCLUSIONS: Doctors do not know their patients' health beliefs, attributing to the whole population the health beliefs of those who most consult the doctor. Users place great hopes in technology, with no relation to age, gender or educational level. PMID- 7888586 TI - [Risk and general precautions during the period of physical conditioning]. PMID- 7888588 TI - [Family and community medicine: journals on a university topic]. PMID- 7888587 TI - [Management of patients with terminal cancer]. PMID- 7888589 TI - [The first National Conference on University and Family Medicine]. PMID- 7888590 TI - [Physical exercise]. PMID- 7888591 TI - [Users-physicians: in search of new ways of detecting problems of quality]. AB - OBJECTIVE: 1) To develop experimentally a method of detecting quality problems in primary care, based on the patient's analysis of his/her overall health-care experience. 2) To perceive and assimilate, from the point of view of the providers, aspects of care related to patients' expectations. DESIGN: A descriptive concurrent study in which "user-doctors" visit their general practitioners as patients. SETTING: Health centres, located in Aragon and Rioja. PARTICIPANTS: Thirty-two doctors doing a doctorate. INTERVENTION: Filling-out of a semi-structured questionnaire and individual elaboration of a report analysing the different care stages: appointment, waiting, visit and referrals. Main variables of the study: accessibility, waiting time, comfort, doctor's interest, quality of information, satisfaction, treatment received. For each stage, in line with prior expectations, the detection of problems, the search for positive aspects and the analysis of the care situation with corrective measures were proposed. MEASUREMENTS AND MAIN RESULTS: Problems detected: difficulty of telephone contact, uncomfortable and lengthy wait, health staff smoking, scant interest from the doctor, no greeting on entry, interruptions during the visit, insufficient information. Positive aspects: facilities in choice of appointment, cordiality of treatment, personal call by the doctor, punctuality. CONCLUSIONS: The method is simple, economical, sensitive in detecting problems felt by the users, and feasible as a complement to other systems used in our ambit. PMID- 7888592 TI - [Is stated income a valid indicator of the socioeconomic status?]. AB - OBJECTIVE: 1) To analyse the validity of the reply to the question on socio economic income included in health questionnaires. 2) To identify other valid indicators of socio-economic status. DESIGN: Crossover and retrospective observation study. SETTING: Community (Molina de Segura Health District). PARTICIPANTS: 1,071 people over 18, selected by means of simple random sampling. INTERVENTIONS: Analysis of 16 questions relating to home furnishing, consumer goods and stated income. We used Factorial Analysis and the ji2 test. RESULTS: We identified three levels by means of the factorial analysis: a) basic--consisting of hot water, washing-machine, absence of damp patches in the house, individual heating and television. b) Intermediate--consisting of car, video and telephone. c) High--with dishwasher, domestic help and air-conditioning. On analysing the relationship between stated income and socio-economic status we detected association to p < 0.001. The basic level answered more often than expected that their income was less than 50,000 pesetas; the intermediate, between 50 and 100,000; and the high, over 101,000. CONCLUSIONS: 1) It is possible to identify the socio-economic profile of the general population by the belonging of selected of determined consumer items. 2) Stated income is a reliable indicator of socio economic status. Despite a tendency to a low reply to the question on income, income is not generally under-declared. PMID- 7888593 TI - [Calculating coronary risk for patients included in the Preventive Activities and Health Promotion Program]. AB - OBJECTIVE: To calculate coronary risk (CR), or the probability of suffering a "coronary event" within five years, for patients between 35 and 65 included in the Preventive Activities and Health Promotion Programme (PAHPP). DESIGN: A descriptive crossover study. SETTING: Manises Health Centre, Valencia. PATIENTS: All the patients between 35 and 65 included in the PAHPP, 431 in all, were selected. For the coronary risk calculation the coefficients and constants of the Dundee Coronary Risk-Disk were used, the variables being gender, systolic arterial pressure, the number of cigarettes and overall cholesterol. MEASUREMENTS AND MAIN RESULTS: Average CR was 5.1% (CI = 4.7-5.4) "coronary events" in five years. CR was less (p = 0.01) in patients aged between 55 and 65. The risk factors (tobacco dependency, arterial Hypertension and Hypercholesterolaemia) were presented in association in 37.7% of cases. The highest CR was found when the three risk factors were presented in association (CR = 14%), when tobacco dependency was associated with hypercholesterolaemia (CR = 10.4%) or with arterial hypertension (CR = 6.4%). CONCLUSIONS: CR can be calculated on the basis of data obtained by PAHPP: The risk factors are frequently presented in association and therefore require multifactorial vision for a correct assessment. Tobacco dependency is the factor which, whether by itself or in association, has most impact on the determination of modifiable CR. PMID- 7888594 TI - [Description of the evolution of a Balint group during 1992: apropos of 16 reported cases]. AB - OBJECTIVE: To describe the evolution of the Balint group (BG) of the Primary Care team at Galdakao (Vizcaya) during 1992 through the analysis of 16 cases. DESIGN: A retrospective, descriptive study. PARTICIPANTS: A psychoanalyst, three paediatricians, three Family and Community medicine third-year residents, a psychologist and eight family doctors. The total number of members of the BG was 16. MEASUREMENTS AND MAIN RESULTS: The evaluative notes of the sessions held were analysed through study of the variables: number of sessions, control of timetable, attendance, age, gender, patient's personal and family case histories, the apparent cause of presentation, its objective and the group's summarised contributions. Results are: 1) Filling-in of 16 evaluative notes out of a total of 24 cases presented (66.7%). 2) The holding of 100% of the planned sessions. 3) The presence of psychopathological personal and/or family histories in 100% of the new cases. 4) Scant number of elderly people or adolescents presented (one and zero respectively). 5) The character of the BG was participatory, interpretative and practical. 6) The type of conflicts presented were summarised in 5 areas: maternity, couple and family, patients and complex situations, mental illness and conflicts of the doctor and/or institution. CONCLUSIONS: 1) The system of data-gathering employed needs changes (16 notes out of 24), as it limits the scope of the results. 2) The low number of elderly people and adolescents presented suggests difficulties in these groups for the doctor. 3) Psychiatric cases suppose a relative weight in this field as generators of conflict, with those coming from a variety of situations of normal clinical practice being more numerous. 4) The BG affects the doctor's personality, making him/her both more sensitive and more capable of reflecting on conflictual situations in everyday clinical practice. PMID- 7888595 TI - Mean residence time concepts for non-linear pharmacokinetic systems. PMID- 7888596 TI - Repeated dose pharmacokinetics of pancopride in human volunteers. AB - The aim of this study was to assess the pharmacokinetic profile of pancopride after repeated oral dose administration of 20 mg pancopride in tablet form once a day for 5 d in 12 healthy male volunteers. Plasma levels were measured by HPLC using a solid phase extraction method and automated injection. The minimum quantification limit of pancopride in plasma was 2 ng mL-1. The maximum plasma concentration (mean +/- SD) after the first dose was 92.5 +/- 41.5 ng ML-1 and tmax was 1.7 +/- 0.9 h. The elimination half-life (t1/2) was 14.3 +/- 6.9 h. The area under the concentration-time curve from zero to infinity (AUC) was 997 +/- 396 ng h mL-1. The maximum plasma concentration (mean +/- SD) at steady state (day 5) was 101.8 +/- 36.9 ng mL-1 and tmax was 2.2 +/- 1.2 h. The elimination half-life (t1/2) was 16.3 +/- 2.7 h and the minimum plasma concentration (Cssmin) was 16.6 +/- 6.9 ng mL-1. The area under the concentration-time curve during the dosing interval (AUCss tau) was 995 +/- 389 ng h mL-1. The average plasma concentration at steady state (Cssav) was 43.3 +/- 16.1 ng mL-1 and the experimental accumulation ratio (RAUC) was 1.34 +/- 0.19, whereas the mean theoretical value (R) was 1.40 +/- 0.29. The results obtained showed a good correlation between the experimental plasma levels and the expected values calculated using a repeated dose two-compartment model assessed by means of the Akaike value. It is concluded that the pharmacokinetics of pancopride are not modified after repeated dose administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888597 TI - The pharmacokinetics and absolute bioavailability of selegiline in the dog. AB - Selegiline is beneficial to Parkinsonian patients as an adjunct to levodopa therapy. Currently no pharmacokinetic data are available for selegiline in the literature, mainly due to lack of analytical methods that can measure concentrations below 10 ng mL-1 in plasma. A sensitive fluorimetric assay based on inhibition of rat brain monoamine oxidase-B (MAO-B) in vitro has been developed to measure selegiline in plasma as low as 0.25 ng mL-1. The pharmacokinetics of selegiline were investigated following intravenous and oral administration to four female mongrel dogs. Each dog received 1 mg kg-1 selegiline in solution via gavage or by an intravenous route separated by one week. The mean terminal half-life, volume of distribution of the central compartment, and systemic clearance of selegiline were 60.24 +/- 9.56 min, 6.56 +/- 0.56 L kg-1, and 159.91 +/- 19.28 mL min-1 kg-1, respectively. After oral administration selegiline appeared to be absorbed rapidly with a tmax and Cmax of 25 +/- 5.8 min and 5.2 +/- 1.36 ng mL-1, respectively. The absolute bioavailability of selegiline in the dog was 8.51 +/- 3.31%. PMID- 7888598 TI - The effect of different routes of administration on the metabolism of morphine: the disposition of morphine and its metabolites after topical application. AB - The disposition of morphine (MOR) and its metabolites in the rabbit was measured after topical administration of its hydrochloride salt (MOR.HCl), and their time course was compared with those after intravenous and oral administration. The area under the plasma concentration-time curve (AUC) ratio of metabolites/MOR after the topical application of MOR.HCl was similar to that after intravenous injection, but differed from that after oral administration. Pharmacokinetic parameters of the disposition of MOR and its metabolites were obtained by a general curve fitting of the time course of plasma concentrations of these compounds after intravenous injection of MOR.HCl and its metabolites, respectively. On the other hand, the time courses of plasma concentrations of the metabolites after intravenous, oral, and topical administration of MOR.HCl were simulated using a simple compartment model without consideration of enterohepatic circulation and the pharmacokinetic parameters obtained as above. The resulting curves of the metabolites agreed well with the observed values except for those after oral administration. These results suggest that no first-pass metabolism of MOR.HCl occurs after percutaneous administration, and that topical administration of this salt is more advantageous than oral administration in terms of bioavailability. PMID- 7888599 TI - A biopharmaceutic approach in designing a controlled release tablet of sodium monofluorophosphate: 1. In vitro and in vivo studies in beagle dogs. AB - The purpose of this study was to develop a controlled release tablet (CRT) of sodium monofluorophosphate (NaMFP) based on biopharmaceutic and pharmacokinetic principles. NaMFP was introduced in the early eighties to treat osteoporosis. The required dose size (200 mg of NaMFP) and time of drug delivery (8.3 h) were theoretically determined based on the pharmacokinetic parameters of fluoride (F ). A CRT was formulated with ethyl cellulose (EC) by the direct compression method. The ratio of drug to polymer was adjusted 1:1, after studying the in vitro release profiles. The release mechanism from the developed dosage form followed the square root of time relationship. This dosage form was evaluated for its in vivo performance in dogs. The pharmacokinetics of F-, after the IV and PO administration of NaMFP, was determined to standardize the animal model. F- followed a two-compartment model and no significant differences were found between the two routes of administration. The bioavailability in dogs was only 60%. The reason for this poor bioavailability was postulated to be the delivery of drug extended beyond the principal sites of absorption of the gastrointestinal tract. Hence, we decided to characterize the absorption sites of NaMFP and to modify the CRT. PMID- 7888600 TI - Drug distribution and a pulmonary adverse effect of intraperitoneally administered doxorubicin niosomes in the mouse. AB - Niosomes (non-ionic surfactant vesicles) prepared from C16G2 (a hexadecyl diglycerol ether), and loaded with doxorubicin, were administered intraperitoneally to male AKR mice at dose levels of 0, 2.5, 5.0, and 10.0 mg kg 1. Free drug was given at 10.0 mg kg-1 by the intraperitoneal route. At a dose level of 10.0 mg kg-1, peak doxorubicin levels in the central compartment were attained faster with the free drug than with the niosome formulation. However, the peak plasma levels were similar for the free drug and the niosome preparation at the 10 mg kg-1 dose level. With doxorubicin administered as the niosome preparation by the intraperitoneal route at 2.5, 5.0, and 10.0 mg kg-1, mean peak plasma concentrations of the drug showed a tendency to be dose-related although the differences were not significant. Over the 24 h period of the experiment, with doxorubicin at 10 mg kg-1, the niosome formulation delivered significantly more drug to the plasma compartment than the free drug (p < 0.05). When doxorubicin was given in niosomes at 2.5, 5.0 and 10.0 mg kg-1 by the intraperitoneal route, the resulting levels of doxorubicin in cardiac tissue were not dose related and the differences not significant and, although the mean peak cardiac-tissue concentration was higher in animals receiving the free drug at 10.0 mg kg-1 intraperitoneally than in mice given intraperitoneal doxorubicin niosomes at this dose level, the differences were again not significant. There were clinical signs of toxicity in mice given doxorubicin-containing niosomes intraperitoneally at 5.0 and 10.0 mg kg-1, and at post-mortem an accumulation of fluid in the pleural cavity was evident. These changes were not seen in mice dosed intraperitoneally with free drug at 10 mg kg-1, or in animals given doxorubicin niosomes intraperitoneally at 2.5 mg kg-1. In mice dosed intraperitoneally with doxorubicin niosomes at 12.0 mg kg-1 and at a dose volume of 0.2-0.4 mL, histological examination of the lungs demonstrated a congestion of the alveolar capillaries, and an increased number of acute inflammatory cells in the alveolar walls. There was no histological evidence of lung toxicity in mice dosed with doxorubicin niosomes at 12.0 mg kg-1 when the formulation was administered with the higher dose volume of 1.8-2.0 mL. Importantly there was no histological evidence of lung toxicity in mice dosed with empty niosomes intraperitoneally or with doxorubicin niosomes given intravenously at 12.0 mg kg 1. PMID- 7888601 TI - Effect of 'unstirred' water layer in the intestine on the rate and extent of absorption after oral administration. AB - The presence of an aqueous diffusion layer or 'unstirred' water layer adjacent to the intestinal membrane has long been regarded as a potential barrier for intestinal absorption of compounds. Theoretical analyses were performed in the present study to quantitatively determine the effect of this layer on the rate and extent of absorption of passively absorbed compounds with different membrane absorption half-lives (10 to 300 min) in humans, dogs, rabbits, rats and mice. Diffusion half-lives across this (40 microns thick) layer were estimated to be 5.8, 2.5, 1.1, 0.65 and 0.32 min, respectively, in the distended intestine of the above five species. These half-lives are reduced by about 5-fold when the intestine is about 80% 'flat' in fasting state. The results of extensive analysis indicate that the presence of such a layer is generally expected to have a relatively mild or insignificant effect on the rate of absorption and an insignificant effect on the extent of absorption. The study also indicates that an aqueous layer of 708 microns has practically no effect on the extent of absorption of progesterone, a highly lipophilic compound, in rats. For prediction of or correlation with the fraction of oral dose absorbed after oral administration, the present study indicates that use of apparent or effective permeability rather than unbiased or true wall (membrane) permeability, as advocated earlier by others, should generally suffice. PMID- 7888602 TI - Variable gastric emptying and discontinuities in drug absorption profiles: dependence of rates and extent of cimetidine absorption on motility phase and pH. AB - The influence of various fasting-state gastrointestinal parameters on variability in absorption of cimetidine was studied using simulation and cimetidine administration as a duodenal infusion and as an oral tablet in fistulated mongrel dogs. In the simulation studies, the frequency of double-peak occurrence in plasma profiles was estimated employing average gastric emptying rates as well as interdigestive-migrating-motor-complex (IMMC) phase lengths that were systematically altered. Emptying rates and phase lengths were modeled as periodic step functions. Simulations indicated that double peaks occur when gastric emptying of the drug begins in early phase I or late phase II/III, which represent the periods of very low, medium, and high gastrointestinal motility, respectively. The incidence is increased for longer phase-I duration and higher elimination rate constants. For a compound with a 2 h elimination or disposition half-life, two concentration maxima (double peaks) were found in 12% of the simulated concentration-time profiles. The double peak frequency in simulated curves was considerably higher for t1/2 < 30 min. When cimetidine was administered to dogs as a duodenal infusion in the active and quiescent motility phases, discontinuous profiles were observed, although the variability of the various parameters was reduced when compared. Pharmacokinetic models were set up that were characterized by multi-segmental input (one- to 3-lag-time models were used) for the profiles resulting from oral and duodenal administration. The lag time for the first process characterized the onset of absorption. A significant difference between phases was detected for infusions at pH 8, where the initial lag time was longer in the quiescent phase. The mean input time (MIT) was calculated as the integral input parameter. There was a tendency for the MIT to be higher for pH 6 infusions than for pH 4 and pH 8. Bioavailability analysis indicated that cimetidine was more rapidly and completely absorbed at pH 8 than at pH 6. Bioavailability was also slightly higher at pH 4 than at pH 6. We concluded that gastric emptying increased the variability of the cimetidine concentration-against-time profiles and that it plays a role with respect to double-peak occurrence, although it is only one of several causative factors. PMID- 7888603 TI - Griseofulvin absorption from different sites in the human small intestine. AB - The site-dependent small-intestinal absorption pattern of griseofulvin was investigated in man. Griseofulvin was chosen as a model substance having extremely low water solubility and moderate lipid solubility. A conventional steady-state perfusion technique (triple-lumen tubing system with a 20 cm test segment) was applied. Dissolved griseofulvin (10.0 mg L-1) was perfused (10 mL min-1) during 160 min into different parts of the small intestine with the middle of the test segment between 85 cm and 270 cm beyond the teeth. Each of the ten healthy volunteers was examined twice with the test segment localized in different regions to allow for intraindividual comparisons. Mean drug absorption rates calculated from intestinal aspirate concentrations were similar in the two intestinal parts (proximal, 15.0 +/- 5.9 micrograms (20 cm min)-1; distal, 16.2 +/- 4.3 micrograms (20 cm min)-1; mean +/- SD). Absorption rate was strongly correlated to the amount of griseofulvin offered to the test segment per unit time. Extrapolating these findings it follows that an amount of griseofulvin, once dissolved, would be absorbed completely (> 99%) along 100 cm of the small intestine. A significant, positive correlation between the rate of transmucosal fluid transport and the absorption rate of griseofulvin was observed in the distal parts investigated. PMID- 7888604 TI - Comparative pharmacokinetics of oxaliplatin (L-OHP) and carboplatin (CBDCA) in mice with reference to circadian dosing time. AB - Carboplatin (CBDCA) and oxaliplatin (I-OHP) are non-nephrotoxic platinum (Pt) compounds, which exert their main respective toxicities on the bone marrow and on the intestinal mucosa in mice. Plasma and red blood cell (RBC) drug dispositions were investigated in 324 male B6D2F1 mice after a single IV injection of CBDCA (72 mg kg-1) or I-OHP (17 mg kg-1). Since the toxicities of either drug largely depended upon circadian dosing time, such a pharmacokinetic study was performed following injection of either Pt complex at a time of low (16 h after light onset HALO), intermediate (0 HALO) or high (8 HALO) toxicity. Pt concentrations in plasma ultrafiltrate (PUF) and in total plasma declined in parallel and became barely detectable by 2 h following CBDCA injection. Conversely, free Pt became undetectable 1 h after I-OHP injection, whereas sustained levels of total Pt were found 24 h post dosing. This suggested that I-OHP had a high binding affinity for plasma proteins. Mean values of t1/2 alpha and mean residence time (MRT) of free Pt for I-OHP (6.7 min and 9.7 min respectively) were half those of CBDCA (12.5 min and 18.1 min respectively). The two drugs had a similar initial volume of distribution (Vdi) of free Pt (10.5 mL) in mice. However, plasma clearance of I OHP was twice as high (1.06 mL min-1) as that of CBDCA (0.58 mL min-1). Free Pt AUCs were eight to ten times lower for I-OHP than for CBDCA. In contrast, erythrocyte Pt AUCs were three to four times as high for I-OHP as for CBDCA. Circadian changes in pharmacokinetic parameters were large, yet limited to the initial distribution phase (C0, t1/2 alpha, Vdi) as well as mean residence time. The smallest Vdi and the fastest plasma elimination occurred when either drug was injected at 0 HALO. The largest Vdi and the longest elimination were however observed at 8 HALO for CBDCA and 16 HALO for I-OHP. No consistent relationship was found for both Pt complexes with regard to circadian changes in blood pharmacokinetics and in target organ toxicities. The major pharmacokinetics differences between CBDCA and I-OHP were related to both protein binding and RBC handling. PMID- 7888605 TI - The bioavailability of diclofenac from enteric coated products in healthy volunteers with normal and artificially decreased gastric acidity. AB - The relative bioavailability of four monolithic enteric coated (MEC) diclofenac products was compared in 16 healthy volunteers. Only one generic product was fully bioequivalent with the reference product Voltaren with regard to AUC, Cmax, and tlag. Two products showed significant differences in tlag. In a second experiment with eight volunteers the influence of increased gastric pH (ranitidine treatment) on the two mutually most differing products was studied. They showed equivalence in AUC, but not in Cmax. Analysis of tlag suggests that the product with the low tlag disintegrates within the non-acid stomach, whereas the product with the long tlag passes the non-acid stomach intact. Several in vitro dissolution tests were conducted. The European Pharmacopeia test did not detect any differences between the products. At pH 5, both with and without mechanical stress, only the product with the shortest tlag released diclofenac. The in vivo results were best predicted by the in vitro dissolution tests performed at several fixed pH values with mechanical stress. PMID- 7888606 TI - Pharmacokinetics of the inodilator XB513 in mice, rats, guinea pigs, rabbits, dogs, and monkeys. PMID- 7888607 TI - Face recognition as a task environment for the reference neuron model of memory. AB - The structure of the reference neuron model and various fine tuning issues were explored within the domain of face recognition. Several faces were presented for the system to learn. Modified versions of one of the faces were then presented, and the system was asked to identify the faces. Increasing amounts of noise were added to the faces and the system's responses were noted. The system proved very capable of accurately identifying modified faces, even rivaling the ability of the human eye. Many interesting tuning and implementation issues were resolved. The system performed best with minimal numbers of neurons involved in the detection process. Another surprising result is that performance achieved was independent of the choice of features to which the neurons responded. PMID- 7888608 TI - Evolution of photosynthetic reaction centers and light harvesting chlorophyll proteins. AB - It is proposed that there is a single evolutionary origin for photosynthetic reaction centers and also for most light-harvesting chlorophyll proteins. It is generally accepted that the purple bacterial reaction center (quinone-reducing photosystem) and the plant and cyanobacterial PSII (oxygen-evolving photosystem) are homologous. It is also apparent that the green sulfur bacterial reaction center is homologous to cyanobacterial PSI (the pyridine nucleotide reducing photosystem). However, it is less obvious that PSI is related to the purple bacterial reaction center. It is herein proposed that PSI represents a gene fusion of the precursors of small light harvesting bacteriochlorophyll proteins from purple bacteria and purple bacterial reaction centers. Furthermore, it is proposed that reaction centers evolved from the membrane-spanning cytochrome b of the cytochrome bc1 complex and that most membrane-spanning cytochromes may have a common origin. PMID- 7888609 TI - Transitions of latency time and oscillation phase on parameter surfaces from models of intracellular calcium ion dynamics. AB - The dynamics of two classical elementary compartmental models stimulating intracellular calcium ion oscillatory behavior are examined in terms of parameter surfaces. It has been found that, along certain lines of instability on surfaces defined by model parameters, the highly non-linear nature of these models produces sharp transitions in the latency time which determines the phase of oscillations once they commence. This sensitivity to initial conditions in deterministic models, along with the stochastic variance inevitably present in actual biological systems, illustrates how two seemingly identical cells activated by identical synchronous stimulation can exhibit oscillatory responses which are out of phase with respect to each other. PMID- 7888610 TI - A study of the singularities in a mathematical model for circadian rhythms. AB - One of the models that has been suggested for describing circadian rhythms mathematically is an extension of the van der Pol equation given by y + 0.5(y2 + y-2 - 3)y + (1 + 0.6 y) y = z + z + z, where y is the oscillating variable, and z is the light intensity assumed to excite the oscillator. In order for the equation to exhibit self-sustained oscillations, z has to be within the oscillatory range (0.847 < z < 3.189). This equation has been shown to simulate several of the features possessed by circadian systems (Wever, R., 1984, Toward a mathematical model of circadian rhythmicity, in: Mathematical Models of the Circadian Sleep-Wake Cycle, M.C. Moore-Ede and C.A. Czeisler (eds.) (Raven Press, New York) pp. 17-79). Physiological experiments have been performed which show that circadian rhythms can have stable singularities. Therefore, it was of interest to investigate whether or not the equation given above also has this property. We have studied the stability of the two singularities of the model system above. One of the singularities is unstable and corresponds to non physiological conditions. The other one is an unstable spiral point if the light conditions are such that oscillations can occur in the system. We conclude that the model mentioned above is unsuitable to describe circadian systems which have stable singularities. The model has been simulated, and pulses have been applied to the system by temporarily changing the value of z to find appropriate conditions forcing the system into its singularity. The strategy to find such pulses is discussed. PMID- 7888611 TI - Exit from mitosis induced by a calcium transient: the relation to the MPF and InsP3 dynamics. AB - Cells divide only after passing through a control point in late G1. This passage is followed by the accumulation of the mitotic cyclin which binds to p34cdc2, allowing for the subsequent phosphorylation and dephosphorylation of the latter protein. It is the active MPF, i.e. the phosphorylated mitotic cyclin-p34cdc2 kinase complex that triggers entry into mitosis. MPF becomes increasingly active as the cell forwards to anaphase, when a sudden increase in InsP3 takes place. This in turn induces a large Ca2+ release in cytosol from internal calcium stores and a calcium-dependent positive feedback control on InsP3-induced calcium release enhances the effect on InsP3-mediated Ca2+ transient. Meanwhile, empty calcium stores signal to plasma membrane for a constant calcium influx at high InsP3 levels. The cytosolic calcium excess is assumed to activate the CaMKll holloenzyme which involves the production of the ubiquitination complex necessary for cyclin degradation and MPF inactivation. Accordingly, a mathematical model was proposed by means of an eight-dimensional dynamical system that yields the time dependence of the main cellular quantities in a picture of the mitosis specific events. PMID- 7888612 TI - The stability of proteinoid microspheres. AB - Proteinoid microspheres are stable hollow spheres of diameter of the order of 5 microns. Their stability is discussed in terms of macroscopic energies. It is shown that bulk and surface energy contributions alone cannot lead to stable microspheres. If electrostatic energy, due to transmembrane voltage, is taken into account, stable hollow spheres are proved to exist. For several reasons, however, this result should not be regarded as the ultimate explanation of microsphere stability. PMID- 7888613 TI - Evolutionary algorithms and a fractal inverse problem. AB - Over the past 30 years, algorithms that model natural evolution have generated robust search methods. These so-called evolutionary algorithms have been successfully applied to a wide range of problems. This paper discusses two types of evolutionary algorithms and their application to a problem in shape representation. Genetic algorithms and evolutionary programming, although both based on evolutionary principles, each place different emphasis on what drives the evolutionary process. While genetic algorithms rely on mimicking specific genotypic transformations, evolutionary programming emphasizes phenotypic adaptation. Results presented show the success of evolutionary programming in solving an example of a fractal inverse problem, but indicate that a genetic algorithm is not as successful. Reasons for this disparity are discussed. PMID- 7888614 TI - Light-induced expression of ipt from Agrobacterium tumefaciens results in cytokinin accumulation and osmotic stress symptoms in transgenic tobacco. AB - Cytokinins are plant growth regulators that induce shoot formation, inhibit senescence and root growth. Experiments with hydroponically grown tobacco plants, however, indicated that exogenously applied cytokinin led to the accumulation of proline and osmotin. These responses were also associated with environmental stress reactions, such as salt stress, in many plant species. To test whether increased endogenous cytokinin accumulation led to NaCl stress symptoms, the gene ipt from Agrobacterium tumefaciens, encoding isopentenyl transferase, was transformed into Nicotiana tabacum cv. SR-1 under the control of the light inducible rbcS-3A promoter from pea. In high light (300 mumol PPFD m-2 s-1), ipt mRNA was detected and zeatin/zeatin glucoside levels were 10-fold higher than in control plants or when transformants were grown in low light (30 mumol PPFD m-2 s 1). High light treatment was accompanied by increased levels of proline and osmotin when compared to low light grown transformed and untransformed control plants. Elevated in planta cytokinin levels induced responses also stimulated by salt stress, suggesting either common or overlapping signaling pathways are initiated independently by cytokinin and NaCl, setting in motion gene expression normally elicited by developmental processes such as flowering or environmental stress. PMID- 7888615 TI - Characterization of a rice gene family encoding root-specific proteins. AB - Two cDNA clones (RCc2 and RCc3) corresponding to mRNAs highly expressed only in root tissues of rice (Oryza sativa L.) seedlings were characterized. Respectively, they encode polypeptides of 146 (14.5 kDa) and 133 amino acids (13.4 kDa) that share high (> 70%) sequence similarity with a polypeptide encoded by a cDNA (ZRP3) encoding an mRNA preferentially expressed in young maize roots. Genomic DNA blot analysis revealed that they are members of a small gene family and RCg2, the gene corresponding to RCc2, was isolated. A 1656 bp 5'-upstream sequence of RCg2 was translationally fused to a beta-glucuronidase (GUS) reporter gene and stable introduction of the chimeric construct into rice was confirmed by PCR and genomic DNA blot analyses. Histochemical analysis of transgenic rice plants containing the full-length chimeric gene showed high levels of GUS activity in mature cells and the elongation and maturation zones of primary and secondary roots, and in the root caps, but no GUS activity was detected in root meristematic regions. Surprisingly, high GUS activity was also detected in leaves of the same plants. This raises the possibility that the RCg2 5'-upstream element may not be sufficient for the proper spatial control of root specificity in transgenic rice. PMID- 7888616 TI - Cloning and developmental expression of pea ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit N-methyltransferase. AB - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) large subunit (LS) N methyltransferase (protein methylase III, Rubisco LSMT, EC 2.1.1.43) catalyzes methylation of the epsilon-amino group of Lys-14 in the LS of Rubisco. With limited internal amino acid sequence information obtained from HPLC-purified peptic polypeptides from Rubisco LSMT, a full-length cDNA clone was isolated utilizing polymerase chain reaction-based technology and conventional bacteriophage library screening. The 1802 bp cDNA of Rubisco LSMT encodes a 489 amino acid polypeptide with a predicted molecular mass of ca. 55 kDa. A derived N terminal amino acid sequence with features common to chloroplast transit peptides was identified. The deduced sequence of Rubisco LSMT did not exhibit regions of significant homology with other protein methyltransferases. Southern blot analysis of pea genomic DNA indicated a low gene copy number of Rubisco LSMT in pea. Northern analysis revealed a single mRNA species of about 1.8 kb encoding for Rubisco LSMT which was predominately located in leaf tissue. Illumination of etiolated pea seedlings showed that the accumulation of Rubisco LSMT mRNA is light-dependent. Maximum accumulation of Rubisco LSMT transcripts occurred during the initial phase of light-induced leaf development which preceded the maximum accumulation of rbcS and rbcL mRNA. Transcript levels of Rubisco LSMT in mature light-grown tissue were similar to transcript levels in etiolated tissues indicating that the light-dependent accumulation of Rubisco LSMT mRNA is transient. This is the first reported DNA and amino acid sequence for a protein methylase III enzyme. PMID- 7888617 TI - Classification and expression of a family of cyclin gene homologues in Brassica napus. AB - In order to investigate the role of cell division in plant development, we isolated several plant genes which encode homologues of animal and yeast cell cycle regulators known as cyclins. Through the use of degenerate primers and the polymerase chain reaction (PCR) we isolated a Brassica sequence which showed homology to the 'cyclin box' functional domain found within cyclin proteins. Southern blot analysis indicated that Brassica napus has a large number of genes containing cyclin box-related sequences. This was further supported by the isolation of cyclin box sequences from six different genomic clones. In addition, we have isolated two different cyclin cDNA clones, BnCYC1 and BnCYC2, from a Brassica napus shoot apical cDNA library. Both of the cDNA clones contain a 'destruction box' regulatory domain similar to animal mitotic cyclins. Northern blot analysis using BnCYC2 shows mRNA levels which correlate well with the level of cell division in various tissues. Messenger RNA abundance was highest in 1-3 mm leaves, root tips and shoot apices. The mRNA detected using BnCYC1 was restricted to young leaves and the shoot apex, suggesting divergent, organ specific roles for cyclin family members. The results demonstrate that the plant cyclin gene family is more extensive than previously demonstrated and consists of genes expressed in all dividing tissues as well as a subset of developmentally specific members. PMID- 7888618 TI - Xylem-specific gene expression in loblolly pine. AB - Two genes preferentially expressed in differentiating xylem of loblolly pine (Pinus taeda L.) were cloned from cDNA and genomic libraries and designated PtX3H6 and PtX14A9. Transcripts of PtX3H6 and PtX14A9 are very abundant in differentiating xylem, less abundant in needles, and very low or non-detectable in embryos and megagametophytes. PtX3H6 contains a putative signal peptide, a threonine-rich region, a proline-rich region, and a hydrophobic tail. Repeats of Pro-Pro-Pro-Val-X-X are similar to repeats found in proline-rich cell wall proteins. The amino acid compositions of PtX3H6 and PtX14A9 are similar to those of arabinogalactan proteins (AGPs). PtX14A9 contains an 8 amino acid sequence similar to amino terminal sequences of ryegrass, carrot and rose AGPs. Upstream sequences have been determined from genomic clones encoding PtX3H6 and PtX14A9. A 7 bp sequence found in the 5' flanking regions of both genes has previously been shown to be involved in the vascular-specific expression of GRP 1.8, a glycine rich protein found in bean. The sequence is also present upstream of another glycine-rich protein from bean, GRP 1.0, and may be partially responsible for the xylem-specific expression of pTx3H6 and PtX14A9. PMID- 7888619 TI - Developmental, circadian and light regulation of wheat ferredoxin gene expression. AB - A genomic clone encoding the precursor of wheat leaf ferredoxin has been isolated and characterised. The uninterrupted PetF gene encodes a polypeptide of 143 amino acid residues, consisting of an N-terminal presequence of 46 amino acid residues and a mature polypeptide of 97 amino acid residues. Southern blot analysis suggests that six copies of the PetF gene are present in the wheat haploid genome. Northern blot analysis has shown that the genes are both developmentally and light regulated in wheat seedlings and provides evidence that a circadian rhythm regulates the steady-state levels of ferredoxin transcripts. The intact wheat gene and several chimeric constructs, containing portions of the 5' upstream region fused to the beta-glucuronidase reporter gene, have been introduced into tobacco plants, but levels of beta-glucuronidase activity above background were not detected, suggesting that the 5'-upstream region is unable to function as a promoter in tobacco plants. PMID- 7888621 TI - Loss of chloroplast transcripts for proteins associated with photosystem II: an early event during heat-bleaching in Euglena gracilis. AB - A shift in the ratio of chlorophyll (Chl) a and Chl b is an early indicator of heat bleaching in Euglena gracilis. This observation prompted us to consider whether or not changes in steady-state levels of chloroplast transcripts and in transcriptional activity could limit the synthesis of Chl a-binding proteins in bleaching plastids. We found that the mature transcripts for CP47 and CP43, the Chl a-binding apoproteins of the proximal antenna of photosystem II, decline sharply very early during bleaching. Our study also shows that transcription of psbB and psbC, the chloroplast genes encoding CP47 and CP43, remains essentially unchanged during the same interval. We conclude that posttranscriptional events, such as mRNA stability, could play a major role in initiating an irreversible loss of chloroplast function in Euglena at a moderately elevated temperature. Lack of these transcripts would eventually impair the assembly of photosystem II in thylakoids. PMID- 7888620 TI - Expression of the betaine aldehyde dehydrogenase gene in barley in response to osmotic stress and abscisic acid. AB - When subjected to salt stress or drought, some vascular plants such as barley respond with an increased accumulation of the osmoprotectant glycine betaine (betaine), being the last step of betaine synthesis catalyzed by betaine aldehyde dehydrogenase (BADH). We report here cloning and characterization of BADH cDNA from barley, a monocot, and the expression pattern of a BADH transcript. An open reading frame of 1515 bp encoded a protein which showed high homology to BADH enzymes present in other plants (spinach and sugar-beet) and in Escherichia coli. Transgenic tobacco plants harboring the clone expressed high levels of both BADH protein and its enzymatic activity. Northern blot analyses indicated that BADH mRNA levels increased almost 8-fold and 2-fold, respectively, in leaves and roots of barley plants grown in high-salt conditions, and that these levels decreased upon release of the stress, whereas they did not decrease under continuous salt stress. BADH transcripts also accumulate in response to water stress or drought, indicating a common response of the plant to osmotic changes that affect its water status. The addition of abscisic acid (ABA) to plants during growth also increased the levels of BADH transcripts dramatically, although the response was delayed when compared to that found for salt-stressed plants. Removal of plant roots before transferring the plants to high-salt conditions reduced only slightly the accumulation of BADH transcripts in the leaves. PMID- 7888622 TI - The phenylalanine ammonia-lyase gene family in Arabidopsis thaliana. AB - Phenylpropanoid derivatives are a complex class of secondary metabolites that have many important roles in plants during normal growth and in responses to environmental stress. Phenylalanine ammonialyase (PAL) catalyzes the first step in the biosynthesis of phenylpropanoids, and is usually encoded by a multi-gene family. Genomic clones for three Arabidopsis thaliana PAL genes containing the entire protein-coding region and upstream and downstream sequences have been obtained and completely sequenced. Two A. thaliana PAL genes (PAL1 and PAL2) are structurally similar to PAL genes that have been cloned from other plant species, with a single intron at a conserved position, and a long highly conserved second exon. Previously identified promoter motifs plus several additional sequence motifs were found in the promoter regions of PAL1 and PAL2. Expression of PAL1 and PAL2 is both qualitatively and quantitatively similar in different plant organs and under various inductive conditions. A third A. thaliana PAL gene, PAL3, differs significantly from PAL1 and PAL2 and other sequenced plant PAL genes. PAL3 contains an additional intron, and its deduced amino acid sequence is less homologous to other PAL proteins. The PAL3 promoter region lacks several sequence motifs conserved between A. thaliana PAL1 and PAL2, as well as motifs described in other genes involved in phenylpropanoid metabolism. A. thaliana PAL3 was expressed at very low levels under the conditions examined. PMID- 7888623 TI - A homologue of the MAP/ERK family of protein kinase genes is expressed in vegetative and in female reproductive organs of Petunia hybrida. AB - The mitogen activated protein (MAP) kinase pathway of eukaryotes is stimulated by many growth factors and is required for the integration of multiple cellular signals. In order to study the function of MAP kinases during plant ovule development we have synthesized a Petunia hybrida ovule-specific cDNA library and screened for MAP protein kinase-related sequences using a DNA probe obtained by PCR. A full-length cDNA clone was identified (PMEK for Petunia hybrida MAP/ERK related protein kinase) and shown to encode a protein related to the family of MAP/ERK protein kinases. Southern blot analysis showed that PMEK is a member of a small multigene family in P. hybrida. The cDNA codes for a protein (PMEK1) of 44.4 kDa with an overall sequence identity of 44% to the products of the mammalian ERK/MAP kinase gene, and the budding yeast KSS1 and FUS3 genes. PMEK1 displays 96 and 80% identity respectively with the tobacco NTF3 and Arabidopsis ATMPK1 kinases, and only 50% to the more distantly related plant MAP kinase MsERK1 from alfalfa. The two phosphorylation sites found in the loop between subdomain VII and VIII in all the other MAP kinases are also present in PMEK1. RNA gel blot and RT-PCR analyses demonstrated that PMEK1 is expressed in vegetative organs and preferentially accumulated in female reproductive organs of P. hybrida. In situ hybridization experiments showed that in the reproductive organs PMEK1 is expressed only in the ovary and not in the stamen. PMID- 7888624 TI - Gene rearrangements in Chlamydomonas chloroplast DNAs are accounted for by inversions and by the expansion/contraction of the inverted repeat. AB - To gain insight into the mutational events responsible for the extensive variation of chloroplast DNA (cpDNA) within the green algal genus Chlamydomonas, we have investigated the chloroplast gene organization of Chlamydomonas pitschmannii, a close relative of the interfertile species C. eugametos and C. moewusii whose cpDNAs have been well characterized. At 187 kb, the circular cpDNA of C. pitschmannii is the smallest Chlamydomonas cpDNA yet reported; it is 56 and 105 kb smaller than those of its C. eugametos and C. moewusii counterparts, respectively. Despite this substantial size difference, the arrangement of 77 genes on the C. pitschmannii cpDNA displays only three noticeable differences from the organization of the corresponding genes on the collinear C. eugametos and C. moewusii cpDNAs. These changes in gene order are accounted for by the expansion/contraction of the inverted repeat and one or two inversions in a single-copy region. In land plant cpDNAs, these kinds of events are also responsible for gene rearrangements. The large size difference between the C. pitschmannii and C. eugametos/C. moewusii cpDNAs is mainly attributed to multiple events of deletions/additions as opposed to the usually observed expansion/contraction of the inverted repeat in land plant cpDNAs. We also found that the mitochondrial genome of C. pitschmannii is a circular DNA molecule of 16.5 kb which is 5.5 and 7.5 kb smaller than its C. moewusii and C. eugametos counterparts, respectively. PMID- 7888625 TI - Isolation and sequence analysis of cDNAs encoding phosphoenolpyruvate carboxykinase from the PCK-type C4 grass Urochloa panicoides. AB - A rabbit antiserum was raised against phosphoenolpyruvate carboxykinase (PCK) purified from Urochloa panicoides, a PCK-type C4 monocot. The antiserum was used to screen a cDNA expression library constructed from U. panicoides leaf poly(A)+RNA. Inserts from immunoreactive clones were used to rescreen the library and obtain three overlapping cDNAs comprising a 2220 bp composite sequence. The single complete open reading frame of 1872 bp encodes PCK1, a 624 amino acid polypeptide with a predicted molecular mass of 68,474 Da. Comparison of PCK1 with other ATP-dependent PCKs indicates that PCK1 is significantly larger, mainly due to an N-terminal extension of greater than 65 residues, and reveals high sequence identity across the central portion of the protein, especially over seven sub sequences. One of these sub-sequences spans motifs common to several ATP utilising enzymes for phosphate and divalent cation binding. The anti-PCK antiserum recognises a 69 kDa polypeptide on immunoblots of either purified PCK or U. panicoides leaf extracts. However, polypeptides of 63, 62, 61 and 60 kDa are also immunoreactive. Amino terminal sequencing of polypeptides from preparations of purified PCK demonstrates that these smaller polypeptides are related to PCK1, and time course experiments show that these polypeptides arise from the breakdown of PCK during isolation. Northern blot analysis indicates that the 2.7 kb PCK mRNA is abundant in green leaves but not in roots or etiolated shoots. Moreover, PCK mRNA levels increase gradually during greening, reaching maximum levels after about 84 h. PMID- 7888626 TI - Molecular characterization of a glyoxysomal citrate synthase that is synthesized as a precursor of higher molecular mass in pumpkin. AB - A cDNA clone for glyoxysomal citrate synthase (gCS) was isolated from a lambda gt11 cDNA library prepared from etiolated pumpkin cotyledons. The cDNA of 1989 bp consisted of a 1548 bp open reading frame that encoded 516 amino acid residues. The deduced amino acid sequence of gCS did not have a typical peroxisomal targeting signal at its carboxyl terminal. A study of expression in vitro of the cDNA and an analysis of the amino-terminal sequence of the citrate synthase indicated that gCS is synthesized as a larger precursor that has a cleavable amino-terminal presequence of 43 amino acids. The predicted amino-terminal sequence of pumpkin gCS was highly homologous to those of other microbody enzymes, such as 3-ketoacyl-CoA thiolase of rat and malate dehydrogenase of watermelon that are also synthesized as precursors of higher molecular mass. Immunoblot analysis showed that the level of gCS protein increased markedly during germination and decreased rapidly during the light-induced transition of microbodies from glyoxysomes to leaf peroxisomes. By contrast, the level of mRNA for gCS reached a maximum earlier than that of the protein and declined even in darkness. The level of the mRNA was low during the microbody transition. These results indicate that the accumulation of the gCS protein does not correspond to that of the mRNA and that degradation of gCS is induced during the microbody transition, suggesting that post-transcriptional regulation plays an important role in the microbody transition. PMID- 7888627 TI - A cdc2 homologue and closely related processed retropseudogenes from Norway spruce. AB - The p34cdc2 protein kinase is a key component in the regulation of the eukaryotic cell cycle and has been conserved during evolution. We have isolated cDNA clones corresponding to a cdc2 gene (cdc2Pa) from the conifer Norway spruce, Picea abies (L.) Karst. The deduced amino acid sequence is 85-90% identical to p34cdc2 homologues from other plants, contains eleven subdomains characteristic for the protein kinase family, and three sequence motifs specific for the cdc2 protein kinases. A partial genomic clone of cdc2Pa reveals two introns at positions identical to intron positions in Arabidopsis thaliana cdc2a. A Southern blot analysis shows that cdc2Pa is a single-copy gene belonging to a family of about 10 related genes. Partial genomic sequences of six of the genes in this family (86-92% identical to cdc2Pa) show distinct features of processed retropseudogenes. These lack introns and contain deletions, insertions and/or non silent point mutations. This result is consistent with the hypothesis that processed retropseudogenes in plants may be common among genes expressed in the apical meristem, that is, in cells which have the potential to take part in the formation of reproductive organs. Although cdc2Pa transcripts were abundant in the epicotyl and thus likely in the apical meristem, we observed no strict coupling of expression to cell division in embryos and seedlings. PMID- 7888628 TI - Complete sequence of the binary vector Bin 19. AB - Despite the widespread use of Bin 19 as a vector for plant transformation, detailed sequence information on its T-DNA region has only recently become available. We now show that the non-T-DNA region, like the T-DNA region, contains several superfluous insertions and find that some functional elements may not contain optimal sequences. Knowledge of the complete 11,777 bp sequence will aid in the construction of exceptionally efficient derivative vectors of approximately half this size. Precise knowledge of restriction sites and removal of unnecessary sequences will facilitate plasmid manipulations and plant transformation. PMID- 7888630 TI - A cDNA clone encoding Brassica calmodulin. AB - A 834 bp cDNA encoding calmodulin (CaM) has been isolated from Brassica juncea. On Northern analysis this cDNA hybridises this cDNA to mRNAs of about 0.9 kb in leaf, silique and peduncle. Genomic Southern analysis indicates the presence of a CaM multigene family in Brassica juncea. Comparison of the predicted amino acid sequence of Brassica CaM with that of Arabidopsis CaM ACaM-2 and ACaM-3 showed 100% homology, which is not unusual, since both plants belong to the family Cruciferae. In situ hybridisation studies on Brassica seedlings using a digoxigenin-labelled RNA probe showed that high levels of CaM mRNA were detected in the leaf primordia and the shoot apical meristem, and to a lesser degree, in the zone of root elongation of the root tip. The occurrence of a higher rate of cell division and growth in these regions than its surrounding tissue may possibly be related to higher levels of CaM mRNA. PMID- 7888629 TI - Post-transcriptional regulation of a salt-inducible alfalfa gene encoding a putative chimeric proline-rich cell wall protein. AB - A cDNA previously shown to identify a salt-inducible root-specific transcript in Medicago sativa was used to screen an alfalfa library for the corresponding genomic sequence. One positive clone was recovered. The nucleotide sequence of a subclone contained a 329 bp 5' region upstream of the first ATG codon, a 1143 bp coding segment, and a 447 bp 3'-untranslated region interrupted by a single 475 bp intron. Translation of the coding segment, which was designated MsPRP2, suggested it encodes a chimeric 40,569 Da cell wall protein with an amino terminal signal sequence, a repetitive proline-rich sequence, and a cysteine-rich carboxyl-terminal sequence homologous to nonspecific lipid transfer proteins. The 3'-untranslated region of MsPRP2 contained a sequence similar to one found to destabilize mRNAs transcribed from the elicitor-regulated proline-rich protein gene PvPRP1. Transcription run-on experiments using nuclei from salt-sensitive and salt-tolerant alfalfa callus suggested that the accumulation of MsPRP2 transcripts in salt-tolerant alfalfa cells grown in the presence of salt is due primarily to increased mRNA stability. The MsPRP2 gene thus may be a useful model for studying post-transcriptional salt-regulated expression of cell wall proteins. PMID- 7888631 TI - Structure of a functional geranylgeranyl pyrophosphate synthase gene from Capsicum annuum. AB - A geranylgeranyl pyrophosphate synthase (GGPPS) gene from Capsicum annuum (bell pepper) was cloned. The nucleotide sequence shows that this gene, like the capsanthin/capsorubin gene but unlike the phytoene synthase gene from C. annuum, is not interrupted by an intron. Southern blot analysis of C. annuum genomic DNA suggests the presence of a single gene highly similar to the cDNA and also of additional related sequences. The present data suggest that this cloned gene is functional. PMID- 7888633 TI - An extrachromosomal fragment of telomeric DNA in wheat. AB - A procedure developed originally for selective extraction of viral (extrachromosomal) DNA from virus-infected mammalian cells was applied to cell nuclei isolated from uninfected wheat embryos. The resulting nuclear extrachromosomal DNA (exDNA) was enriched for telomere-type sequences by isopycnic centrifugation and inserted into the Sma I site of pUC119. A cloned DNA fragment (241 bp) was found to consist primarily of tandemly repeated heptamere units of the same sequence (5'-CCCTAAA-3') that is known to predominate in telomeric DNA of Arabidopsis thaliana. Hybridization experiments indicate that extrachromosomal telomeric repeats are abundant in resting embryos and disappear rapidly during germination. PMID- 7888632 TI - An apple polyphenol oxidase cDNA is up-regulated in wounded tissues. AB - A full-length cDNA clone encoding apple (Malus domesticus) polyphenol oxidase (PPO) was isolated from a fruit peel cDNA library. Southern analysis indicated that apple PPO is encoded by a divergent multigene family. By northern analysis, PPO mRNA was only detected in a fruit sample taken one week after full bloom. PPO mRNA accumulated in wounded tissues, and also in peel tissue showing the symptoms of superficial scald, a post-harvest disorder. The induction of PPO mRNA provides the first evidence for transcriptional control of PPO expression after wounding or the manifestation of a physiological disorder. PMID- 7888634 TI - The role of neurotrophins during successive stages of sensory neuron development. AB - Neurotrophins comprise a family of basic homodimeric proteins. The isolation of the first two neurotrophins, nerve growth factor and brain-derived neurotrophic factor, was based on the ability of these proteins to promote the survival of embryonic neurons. However, the identification of additional neurotrophins by homology screening together with recent work on these proteins has shown that neurotrophins do more than just regulate neuronal survival. Neurotrophins influence the proliferation and differentiation of neuron progenitor cells and regulate the expression of several differentiated traits of neurons throughout life. Moreover, the influence of neurotrophins on survival is more complex than originally thought; some neurons switch their survival requirements from one set of neurotrophins to another during development and several neurotrophins may be involved in regulating the survival of a population of neurons at any one time. Most of what is known of the developmental physiology of neurotrophins has come from studying neurons of the peripheral nervous system. Quite apart from the accessibility of these neurons and their progenitor cell populations, investigation of the actions of neurotrophins on several well-characterised populations of sensory neurons has permitted the age-related changes in the effects of neurotrophins to be interpreted in the appropriate developmental context. In this review I provide a chronological account of the action of neurotrophins in neuronal development with special reference to sensory neurons. PMID- 7888635 TI - Deciphering the MAP kinase pathway. AB - MAP kinases (MAPK) are serine/threonine kinases which are activated by a dual phosphorylation on threonine and tyrosine residues. Their specific upstream activators, called MAP kinase kinases (MAPKK), constitute a new family of dual specific threonine/tyrosine kinases, which in turn are activated by upstream MAP kinase kinase kinases (MAPKKK). These three kinase families are successively stimulated in a cascade of activation described in various species such as mammals, frog, fly, worm or yeast. In mammals, the MAP kinase module lies on the signaling pathway triggered by numerous agonists such as growth factors, hormones, lymphokines, tumor promoters, stress factors, etc. Targets of MAP kinase have been characterized in all subcellular compartments. In yeast, genetic epistasis helped to characterize the presence of several MAP kinase modules in the same system. By complementation tests, the relationships existing between phylogenetically distant members of each kinase family have been described. The roles of the MAP kinase cascade have been analyzed by engineering various mutations in the kinases of the module. The MAP kinase cascade has thus been implicated in higher eukaryotes in cell growth, cell fate and differentiation, and in low eukaryotes, in conjugation, osmotic stress, cell wall construct and mitosis. PMID- 7888636 TI - Bibliographic update: transforming growth factors. PMID- 7888637 TI - [Individual resistance to hypoxia of the body and nerve cells]. PMID- 7888638 TI - [The effect of exogenous acetylcholine on the effectiveness of neuromuscular transmission in rat diaphragm fatigue]. PMID- 7888639 TI - [The effect of dialysis membranes on lipid peroxidation in erythrocytes of patients with terminal renal failure]. PMID- 7888640 TI - [The modulating effect of carnosine and related compounds on the respiratory burst of leukocytes, activated by barium sulfate]. PMID- 7888641 TI - [Distribution of the peptide morphogen hydra--a head growth activator in rat organs after intravascular administration of the tritiated peptide]. PMID- 7888642 TI - [Second messengers in modulating cholinoreceptors in Helix neurons by amiridine]. PMID- 7888643 TI - [Effect of immunization with sheep erythrocytes on rat behavior]. PMID- 7888644 TI - [Effectiveness of action of bronchodilators is determined by electrostatic interactions]. PMID- 7888646 TI - [Variants in the secondary immune response in mice of lines CBA and C57Bl/6]. PMID- 7888645 TI - [Dynamics of expression of the complex of activation markers in human peripheral blood CD4+, CD8+ lymphocytes during polyclonal stimulation in vitro]. PMID- 7888647 TI - [Formation of colonies of clonogenic stromal precursors in bone marrow and spleen cell cultures in the presence of streptococcal antigens in culture media]. PMID- 7888648 TI - [Study of the specificity of monoclonal antibodies, obtained by immunizing mice with a culture of streptococcus group A, treated with pepsin]. PMID- 7888649 TI - [Comparison of the efficacy of topical and subcutaneous administration of tactivin for correcting secondary immunodeficiencies of young children]. PMID- 7888650 TI - [Interline features of secondary immune response in mice]. PMID- 7888651 TI - [Regulation of the therapeutic and toxic effect of cardiac glycosides by electromagnetic radiation, alternating magnetic, and electric fields]. PMID- 7888652 TI - [Reaction of lung tumor transplants to irradiation and platinum compounds in a subcapsule test]. PMID- 7888653 TI - [The effect of synthetic analogs of dermorphin on corneal and tongue epithelium cell division in white rats]. PMID- 7888654 TI - [Structural basis for barrier properties of the pancreatic main duct epithelium of some mammals]. PMID- 7888655 TI - [Microcirculatory disorders in the rat brain in neurosis]. PMID- 7888656 TI - [Change in the morphofunctional state of the thyroid gland during combined action of hypokinesis and cold]. PMID- 7888657 TI - [Structure-functional changes in the brain of rats with various types of behavior in the distant period of circulatory hypoxia]. PMID- 7888658 TI - [Morphological analysis of the thymus of white rats with a tumor during experimental chemotherapy and its combination with the activated effects of an alternating magnetic field]. PMID- 7888659 TI - [Indications for radical correction of common arterial branch with marked pulmonary hypertension]. PMID- 7888660 TI - [Morphofunctional characteristics of human lactotropic adenomas in cell cultures]. PMID- 7888661 TI - [Cellular mechanisms of genetically determined hypertrophic cardiomyopathy in rats of line W/SSM]. PMID- 7888662 TI - [Postradiation demyelinating changes of the optic nerve]. PMID- 7888663 TI - [Correction of hyperlipidemia in patients with gallstones as a method of improving results of extracorporeal lithotripsy]. PMID- 7888664 TI - Detection of minimal residual disease in acute leukemia: methodologic advances and clinical significance. PMID- 7888665 TI - A novel class of zinc finger/leucine zipper genes identified from the molecular cloning of the t(10;11) translocation in acute leukemia. AB - A novel class of conserved transcription factors has been identified from the molecular cloning of AF10, the gene involved in the t(10;11)(p12;q23) translocation of acute myeloid leukemias. AF10 encodes a 109-kD protein of 1,027 amino acids and contains an N-terminal zinc finger region and a C-terminal leucine zipper. These structures have been found to be conserved in sequence and position in three other proteins, AF17, BR140, and a previously unrecognized Caenorhabditis elegans gene, provisionally named CEZF. The overall structure, level of sequence conservation, and expression pattern suggest that these genes encode a new class of transcription factors, some of which are targets for chromosomal translocation in acute leukemia. PMID- 7888666 TI - Interleukin-5 signaling in human eosinophils involves JAK2 tyrosine kinase and Stat1 alpha. AB - Signaling by a wide variety of cytokines, including interferons, interleukins, and growth factors, involves activation of JAK kinases and Stat (Signal transducers and activators of transcription) proteins. At present, not much is known about the molecular mechanisms by which interleukin-5 (IL-5) exerts its diverse biologic effects. Human eosinophils are one of the most important target cells for IL-5 and were used here to study IL-5 signaling in a primary human cell. IL-5 induced rapid and transient tyrosine phosphorylation of JAK2. Moreover, IL-5 induced at least two DNA-binding complexes, using nuclear extracts from normal human eosinophils and the IL-6/interferon-gamma response element of the ICAM-1 promoter (ICAM-1 pIRE) in an electromobility shift assay. From supershift experiments it was concluded that one DNA-binding complex contained Stat1 alpha, probably as a homodimer. Both DNA-binding complexes were inhibited by a phosphotyrosine antibody (4G10), suggesting that tyrosine phosphorylation is required for complex formation. IL-3 and granulocyte-macrophage colony stimulating factor induced, similar to IL-5, two DNA-binding complexes in human eosinophils, including Stat1 alpha. These data show for the first time that molecular mechanisms of IL-5 signaling in human eosinophils involve members of the JAK kinase family as well as members of the Stat family. PMID- 7888667 TI - Metabolic correction of congenital erythropoietic porphyria by retrovirus mediated gene transfer into Epstein-Barr virus-transformed B-cell lines. AB - Congenital erythropoietic porphyria (CEP) is an inherited metabolic disorder resulting from the accumulation of porphyrins because of defective uroporphyrinogen III synthase (UROIIIS). This autosomal recessive disorder is phenotypically heterogeneous with respect to the age of onset and the severity of the symptoms. Different exonic point mutations in the UROIIIS gene have been identified, providing phenotype-genotype correlations in this disease. Severe cases may be treated by bone marrow transplantation and are potential candidates for somatic gene therapy. Epstein-Barr virus-transformed B-cell lines from patients with CEP provide a model system for the disease. We have used retrovirus mediated expression of UROIIIS to restore enzymatic activity in a B-cell line from a patient. We have also demonstrated the metabolic correction of the disease, ie, porphyrin accumulation into the deficient transduced cells was reduced to the normal level. These data show the potential of gene therapy for this disease. PMID- 7888668 TI - Induction of sequence-specific DNA-binding factors by erythropoietin and the spleen focus-forming virus. AB - The signal transduction mechanism of erythropoietin (Epo), which regulates growth and differentiation of erythroid cells, is still unclear. Recent studies showing the activation by various ligands of a group of proteins called Stat (signal transducers and activators of transcription) proteins raised the possibility that such proteins may also be involved in the Epo signal transduction pathway. In this report, we show that Epo induces factors that specifically bind to the sis inducible element and the gamma response region of the Fc gamma receptor factor I gene in the Epo-dependent mouse erythroleukemia cell line HCD-57. These factors contain phosphotyrosine and antibodies against Stat1 and Stat3 proteins reacted with them. In HCD-57 cells infected with Friend spleen focus-forming virus, which now grow in an Epo-independent manner, the DNA-binding factors were constitutively activated even in the absence of Epo. These results suggest that the factors induced by Epo contain components identical or related to known Stat proteins. It is also suggested that continuous activation of these DNA-binding factors may be responsible for the ability of spleen focus-forming virus to abrogate the Epo-dependence of HCD-57 cells and cause erythroleukemia in susceptible mice. PMID- 7888669 TI - Fetal liver generates low CD4 hematopoietic cells in murine stromal cultures. AB - We have demonstrated that 0.2% to 11% of cells from the fetal liver (FL) reacted specifically with high concentrations of anti-CD4 monoclonal antibody (MoAb). CD4+ cells from FL were similar in surface phenotype and fluorescence characteristics to the CD4+ population found previously in adult bone marrow (BM). FL and BM cells were seeded in cultures that allow differentiation to primitive precursors. FL cells released many low CD4+ and low Thy+ cells in the supernatant, while BM cells seeded under the same conditions did not. We studied the nonadherent cells harvested from 10-day FL cultures (greater than 90% low CD4+). In methylcellulose, they were able to produce more colonies that appear to be characteristic of earlier stages in the hierarchy of hematopoietic precursors (especially erythroid bursts and colonies composed of both myeloid and erythroid elements) in comparison with CD4- cells from 10-day BM cultures. CD4+ cells harvested from FL cultures initiated secondary cultures containing both a stromal layer and large hematopoietic colonies when replated under conditions similar to those of primary cultures. Furthermore, a limited number of CD4+ cells from 10 day FL cultures were able to repopulate lethally irradiated mice. Although we cannot formally exclude the possibility that the low CD4 cells produced in FL cultures were derived exclusively from the proliferation of the few CD4 cells found in fresh FL, the dynamic analysis of the development of these cells in culture favors the generation of this important population from a CD4- subset of hematopoietic stem cells (HSCs). We speculate that FL contains a prevalent population of very primitive cells not expressing the CD4 antigen, tentatively called "pre-low CD4 precursors." These primitive cells can differentiate into low CD4+ cells that share many characteristics with pluripotent HSCs of the adult type. These data indicate the possibility of using hematopoietic progenitors obtained by the expansion/differentiation of fetal stem cells in culture for transplantation purposes. PMID- 7888670 TI - In vitro characterization of the human recombinant soluble granulocyte-macrophage colony-stimulating factor receptor. AB - We have cloned, expressed, and partially purified a naturally occurring, truncated, soluble form of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha subunit to investigate its biochemical and biologic properties. The soluble receptor species lacks the transmembrane and cytoplasmic domains that are presumably removed from the intact receptor cDNA by a mechanism of alternative splicing. The resulting soluble 55- to 60-kD glycosylated receptor species binds GM-CSF with a dissociation constant (kd) of 3.8 nmol/L. The soluble GM-CSF receptor successfully competes for GM-CSF binding not only with the transmembrane-anchored GM-CSF receptor alpha subunit but also with the native oligomeric high-affinity receptor complex. In addition, in human bone marrow colony-forming assays, the soluble GM-CSF receptor species can antagonize the activity of GM-CSF. Our data suggest that the soluble GM-CSF receptor may be capable of acting in vivo as a modulator of the biologic activity of GM-CSF. PMID- 7888671 TI - High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance) AB - Resistance to activated protein C (APC) is a common inherited risk factor for venous thrombosis, which is associated with a mutation in coagulation factor V (factor V Leiden). We investigated the risk of venous thrombosis in individuals homozygous for this abnormality. We determined the factor V Leiden genotype in 471 consecutive patients aged less than 70 years with a first objectively confirmed deep-vein thrombosis and in 474 healthy controls. We found 85 heterozygous and seven homozygous individuals among the cases with thrombosis and 14 heterozygous individuals among the control subjects. The expected number of homozygous individuals among the controls was calculated from Hardy-Weinberg equilibrium and estimated at 0.107 (allele frequency, 1.5%). Whereas the relative risk was increased sevenfold for heterozygous individuals, it was increased 80 fold for homozygous individuals. These patients experienced their thrombosis at a much younger age (31 v 44 years). The homozygous individuals were predominantly women, most likely due to the effect of oral contraceptives. Because of the increased risk of thrombosis with age, the absolute risk becomes most pronounced in older patients, both for heterozygous and homozygous individuals. For the homozygous individuals, the absolute risk may become several percentage points per year. This implies that most individuals homozygous for factor V Leiden will experience at least one thrombotic event in their lifetime. PMID- 7888672 TI - Six point mutations that cause factor XI deficiency. AB - We have identified six novel types of mutation that cause factor XI deficiency, an inherited bleeding disorder. Two are point mutations that interfere with the normal splicing of exons in the mRNA and four are point mutations that result in amino acid substitutions. One of these amino acid substitutions (Asp 16-->His) is near the amino terminal end of the protein. The other three amino acid substitutions (Leu 302-->Pro, Thr 304-->Ile, and Glu 323-->Lys) are in the fourth apple domain, a region that mediates dimerization of identical subunits of factor XI. All four amino acid substitutions cause a reduction in the amount of factor XI secreted from cells grown in vitro. PMID- 7888673 TI - Depolymerized holothurian glycosaminoglycan with novel anticoagulant actions: antithrombin III- and heparin cofactor II-independent inhibition of factor X activation by factor IXa-factor VIIIa complex and heparin cofactor II-dependent inhibition of thrombin. AB - The inhibition mechanism of a polysaccharide anticoagulant, depolymerized holothurian glycosaminoglycan (DHG), was examined by analyzing its effects on the clotting time of human plasma depleted of antithrombin III (ATIII), of heparin cofactor II (HCII), or of both heparin cofactors. The effect exerted by this agent on the activation of prothrombin and factor X in purified human components were also examined and all effects were compared with those of other glycosaminoglycans (GAGs). The capacity of DHG to prolong activated partial thromboplastin time was not reduced in ATIII-depleted, HCII-depleted, HCII depleted, or ATIII- and HCII-depleted plasma, whereas its capacity to prolong prothrombin time and thrombin clotting time was reduced in HCII-depleted plasma. DHG inhibited the amidolytic activity of thrombin in the presence of HCII with a second order rate constant of 1.2 x 10(8) (mol/L)-1 min-1. These results indicated that DHG has two different inhibitory activities, one being an HCII dependent thrombin inhibition and the other an ATIII- and HCII-independent inhibition of the coagulation cascade. The heparin cofactors-independent inhibitory activity of DHG was investigated in the activation of prothrombin by factor Xa and in the activation of factor X by tissue factor-factor VIIa complex or by factor IXa. DHG significantly inhibited the activation of factor X by factor IXa in the presence of factor VIIIa, but not in the absence of factor VIIIa. The interaction between DHG and factors IXa, VIIIa, and X was investigated with a DHG-cellulofine column, on which DHG had strong affinity for factors IXa and VIIIa. These findings show that the heparin cofactors-independent inhibition exhibited by DHG was caused by inhibition of the interaction of factor X with the intrinsic factor Xase complex, probably by binding to the factor IXa-factor VIIIa complex. PMID- 7888674 TI - Role of endogenous cytokines secretion in radioprotection conferred by the immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate. AB - The immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate (AS101) has previously been found by us to have radioprotective properties when injected into mice before sublethal and lethal doses of irradiation. AS101 also was found to protect mice from hematopoietic damage caused by various chemotherapeutic drugs. Based on these findings, phase II clinical trials with cancer patients treated with AS101, in combination with chemotherapy, are currently underway. In the present study, we wanted to assess the role of several cytokines in the radioprotection conferred by AS101. We show that the administration of neutralizing antibodies against interleukin-1 (IL-1) receptor, IL-6 receptor, IL 6, tumor necrosis factor (TNF), or stem cell factor (SCF) completely abrogates the ability of AS101 to increase the survival of lethally irradiated mice. Moreover, the injection of each of these antibodies reduces the ability of AS101 to increase the number of BM, spleen cells, and the number of circulating neutrophils, lymphocytes, and platelets in irradiated mice. In addition, these antibodies abrogate the enhancing effect of AS101 on the secretion of IL-3, IL-6, and granulocyte-macrophage colony-stimulating factor, all of which decrease significantly in sublethally irradiated mice. By contrast, the injection of anti IL-2 receptor antibody or control Igs to AS101-treated mice does not interfere with the radioprotective effects of the compound. These results suggest a role for IL-1, IL-6, TNF alpha, and SCF in the radioprotective effect of AS101. Because cytokine toxicity remains a significant concern, the clinical application of AS101, which has no toxicity, is particularly valuable. PMID- 7888676 TI - Hodgkin and Reed-Sternberg cells do not carry T-cell receptor gamma gene rearrangements: evidence from single-cell polymerase chain reaction examination. AB - Hodgkin and Reed-Sternberg (H&RS) cells are generally accepted to be the neoplastic cells of Hodgkin's disease (HD), even though they represent only a minority of the cellular infiltrate in affected tissues. Recent immunologic studies and Southern blot analyses of DNA extracted from whole lymph node tissue favored, but did not convincingly prove a lymphoid origin of H&RS cells. To detect rearrangements of the T-cell receptor gamma chain (TCR gamma) genes at the single-cell level as an indication of early T-cell lymphoid differentiation, we isolated H&RS cells by micromanipulation from cytospin preparations of fresh biopsy material. TCR gamma chain rearrangement was detected by polymerase chain reaction using four "forward primers" that were constructed corresponding to all four V families and two "reverse primers" corresponding to consensus sequences of J segments. Rearrangements of all V families in combination with the different J segments were detected in human peripheral blood and tonsillar T cells. Although rearrangements of TCR gamma chain genes were shown in single cells of 10 of 10 T cell leukemias, no rearrangement of these genes was found in single H&RS cells from 13 consecutive patients with HD. Our results indicate that H&RS cells from the vast majority of cases are not derived from T cells. This finding may have implications for the pathogenesis of HD and the development of more effective treatment regimens. PMID- 7888675 TI - p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. AB - Conventional cytogenetic analysis in B-cell chronic lymphocytic leukemia (B-CLL) has been very difficult, and the prognostic significance of specific chromosome aberrations is under discussion. Recent improvements in fluorescence in situ hybridization (ISH) techniques have provided an alternative approach for the detection of chromosome aberrations. Here, an interphase cytogenetic study was performed to analyze the incidence and prognostic significance of a p53 gene deletion in B-CLL and related disorders. We studied mononuclear cells from 100 patients with chronic B-cell leukemias [B-CLL, 90 patients; B-prolymphocytic leukemia (B-PLL), 7; Waldenstrom's macroglobulinemia (WM), 3] by fluorescence ISH with a genomic p53 DNA probe. In a subset of patients, additional G-banding analysis and single strand conformation polymorphism (SSCP) analysis was performed. Seventeen of the 100 patients [17%; B-CLL, 11 of 90 (12%); WM, 1 of 3; B-PLL, 5 of 7] exhibited a monoallelic p53 gene deletion by ISH. G-banding analysis demonstrated abnormalities of chromosome 17 in 13 of these 17 patients, all leading to loss of band 17p13. SSCP analysis showed aberrant bands in 9 of 14 patients with a p53 gene deletion. None of 12 patients with a p53 gene deletion compared with 20 of 36 patients (56%) without a deletion responded to therapy with fludarabine or pentostatin (P < .001). The difference in survival probabilities from the time of diagnosis and from the start of treatment with purine analogs between the two groups was highly significant (P < .001). In multivariate analysis, p53 gene deletion was the strongest prognostic factor for survival. In conclusion, p53 gene deletion predicts for non-response to therapy with purine analogs and for poor survival in chronic B-cell leukemias. PMID- 7888677 TI - High-dose sequential chemoradiotherapy in multiple myeloma: residual tumor cells are detectable in bone marrow and peripheral blood cell harvests and after autografting. AB - Based on preliminary encouraging results in terms of response rate and survival, high-dose chemoradiotherapy has gained considerable interest in the treatment of patients with multiple myeloma (MM). We have evaluated the presence of residual myeloma cells in 15 of 18 patients enrolled in a high-dose sequential (HDS) chemoradiotherapy program followed by autografting. Our analysis has been performed both on bone marrow (BM) and peripheral blood (PB) cell harvests and after autografting. As it has been recently shown that B cells clonally related to malignant plasma cells are detectable in MM patients, we have developed a polymerase chain reaction (PCR)-based strategy to detect both residual B cells and plasma cells using clone-specific sequences derived from the rearrangement of Ig heavy chain (IgH) genes. The complementarity-determining regions (CDR) of IgH genes have been used to generate tumor-specific primers and probes. The constant (C) region usage defined the differentiation stage of residual myeloma cells. We report that plasma cells were detectable in PB and BM cell harvests and after transplantation in all assessable patients, irrespective of disease status. B cells were detectable in a consistent proportion of BM and PB samples at diagnosis, but only in one case at the time of PB and BM cell harvests. These cells became sometimes detectable after transplantation. Whether residual myeloma cells are clonogenic and contribute to relapse is currently unknown, and further investigations are required. PMID- 7888679 TI - Overexpression of the MDM2 gene by childhood acute lymphoblastic leukemia cells expressing the wild-type p53 gene. AB - The wild-type (wt) p53 tumor suppressor gene is commonly inactivated in human malignancies, either by mutations or by loss of expression. An additional proposed mechanism for inactivation of wt-p53 is amplification of the murine double minute 2 (MDM2) gene and overexpression of the MDM2 protein, which binds to p53 and eliminates its tumor suppressor function. To investigate a potential role for MDM2 in the inactivation of wt-p53 in pediatric acute lymphoblastic leukemia (ALL), we examined the expression of MDM2 and p53, as well as the occurrence of p53 mutations and possible amplification of the MDM2 gene, in 19 pediatric ALL cell lines and one pediatric acute myelogenous leukemia (AML) line. Although we did not find significant amplification of the MDM2 gene in any of the leukemic lines, we detected overexpression of MDM2 in all 10 lines that expressed wt-p53. Of the 10 lines without overexpression of the MDM2 gene, six (including the AML line) did not express p53, and four expressed mutant p53 with single point mutations in exons 7 and 8. To determine whether primary leukemic cells showed a similar correlation, we analyzed the original cryopreserved leukemic bone marrow cells from seven patients from whom cell lines were established. We obtained similar results from both the primary leukemic cells and the corresponding cell lines: overexpression of MDM2 was present in primary cells that expressed wt-p53 but not in cells that lacked expression of wt-p53. These findings suggest an important role for MDM2 in the pathogenesis of pediatric ALL in which leukemic cells express wt-p53. PMID- 7888678 TI - Splenic lymphoma with villous lymphocytes involves B cells with extensively mutated Ig heavy chain variable region genes. AB - Splenic lymphoma with villous lymphocytes (SLVL) is a recently defined subgroup of chronic B-cell lymphoproliferative diseases. The characteristic morphology of the tumor cells, together with phenotypic and cytogenetic findings, indicate that it is a distinct entity, but the nature of the cell or origin and its relationship to other low-grade lymphomas is unclear. For B-cell tumors, analysis of the variable region heavy chain (VH) genes used to encode the clonal Ig has shown marked differences between histologic categories, both in gene usage and extent of somatic mutation. An investigation of VH genes used in five typical cases of SLVL has shown somatic hypermutation from germline sequences in all cases, indicating that the cell of origin has been exposed to the hypermutation mechanism. However, no clonal heterogeneity was detectable, demonstrating that the tumor cell does not accumulate further mutations. These characteristics are similar to those found in mature postfollicular B cells, such as plasma cells. The distribution of mutations leading to replacement amino acids differed among the cases, with three of five cases showing clear evidence for antigen selection. PMID- 7888680 TI - Role of the sialophorin (CD43) receptor in mediating influenza A virus-induced polymorphonuclear leukocyte dysfunction. AB - Polymorphonuclear leukocytes (PMNLs) exposed to influenza A virus (IAV) undergo activation of the respiratory burst followed by depression of cell function when subsequently exposed to particulate or soluble stimuli. The effect of IAV on PMNLs is likely to be mediated through the attachment of IAV to one or more specific receptors. Recently, IAV has been shown to bind to the sialophorin protein (CD43) receptor on PMNL plasma membranes. The present study was performed to determine if the sialophorin receptor was responsible for IAV-induced PMNL dysfunction. When PMNLs were incubated with IAV or CD43 monoclonal antibody (MoAb) for 30 minutes and then exposed to a secondary particulate (opsonized zymosan) or soluble (FMLP or phorbol 12-myristate 13-acetate) stimulus, there was significant depression of the PMNL chemiluminescence response compared with the equivalent control (P < .05). When PMNL were incubated with the CD43 MoAb and then cross-linked with a goat antimouse IgG antibody, no depression of PMNL function occurred upon secondary stimulation. Exposure of cells to IAV aggregates also eliminated the PMNL dysfunction that normally occurs due to the virus. Similar to IAV, PMNL dysfunction due to the CD43 MoAb could be overcome by priming the cells with granulocyte-macrophage colony-stimulating factor. These findings indicate that IAV-induced PMNL dysfunction is mediated, at least in part, through the sialophorin receptor. PMID- 7888681 TI - Isolation of a novel macrophage-specific gene by differential cDNA analysis. AB - To analyze myelomonocytic differentiation we have used the approach of differential cDNA analysis to isolate novel genes that are preferentially expressed in mature macrophages. Differential screening of a macrophage cDNA library led to the identification of a novel cDNA that showed macrophage lineage- and differentiation stage-specific expression. Transcripts from the gene, which we have termed Mpg-1, are found at a high level in mature human and murine macrophages and at a moderate level in certain myelomonocytic cell lines. The expression of Mpg-1 was found to increase when murine fetal liver hematopoietic progenitor cells were induced to differentiate into macrophages. An Mpg-1 specific transcript was not detected in a wide variety of other tissues and cell lines. The DNA sequence of Mpg-1 (4,214 bp) was obtained from a series of overlapping cDNA, 3' rapid amplification of cDNA ends (RACE), and genomic clones. Primer extension analysis predicted the existence of multiple transcription start sites, ranging from 26 to 117 bp upstream of the 5' proximal ATG of the open reading frame. The predicted 669-amino acid, Mpg-1-encoded protein has potential glycosylation and phosphorylation sites in addition to a signal sequence. The core protein is predicted to have a molecular weight of 71 to 74 kD. Computer assisted local similarity searches indicate that Mpg-1 is a novel gene that may share a distant ancestry to perforin, a lytic protein found in cytotoxic T lymphocytes and natural killer cells. PMID- 7888682 TI - Extruded erythroblast nuclei are bound and phagocytosed by a novel macrophage receptor. AB - Resident bone marrow macrophages (RBMM) play an important role in clearance of nuclei extruded from late-stage erythroblasts (Eb). To investigate the nature of macrophage receptors involved in this process, extruded erythroblast nuclei (EEN) were purified by cultivation of erythroblasts with erythropoietin, followed by density gradient centrifugation. By electron microscopy, the majority of free nuclei had an intact plasma membrane. EEN bound avidly to RBMM in a divalent cation-independent manner at both 4 degrees C and 37 degrees C. The use of specific monoclonal antibodies (MoAbs) and inhibitors showed that this adhesive interaction was not mediated by previously characterized macrophage receptors involved in recognition of either developing hematopoietic cells or apoptotic cells. The EEN receptor was expressed on resident macrophages isolated from murine bone marrow, spleen, lymph node, and peritoneal cavity, but was completely absent from alveolar macrophages. Despite high levels of EEN binding to RBMM, few were phagocytosed even after prolonged culture. Phorbol myristate acetate (PMA) was found to stimulate phagocytosis, suggesting that this is a regulated process. These findings indicate that EEN are recognized by a novel macrophage receptor and that recognition may be triggered during the membrane remodeling that accompanies enucleation. PMID- 7888683 TI - Heterogeneous PIG-A mutations in different cell lineages in paroxysmal nocturnal hemoglobinuria. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal defect of hematopoietic stem cells in which affected cells are characterized by the lack of glycosylphosphatidylinositol (GPI)-anchored proteins. The lesion in PNH lies in the defective synthesis of N-acetyl-D-glucosaminyl-phosphatidylinositol (GlcNAc Pl), the first intermediate in GPI biosynthesis. Reintroduction of the PIG-A gene into GPI(-) patient cells reportedly complements this defect. We have analyzed here PIG-A transcripts of six PNH patients. GPI+ and GPI- cell lines from each individual were used, ie, Epstein-Barr virus-transformed B-lymphoblastoid cell lines, T-cell lines, and natural killer cell clones. Reverse transcriptase polymerase chain reaction and sequencing showed three different PIG-A splicing variants in GPI+ cell lines, in which the largest transcript contained the wild type PIG-A coding region sequence. GPI-deficient cell lines showed abnormal splicing variants. Sequencing of PIG-A complementary DNA and genomic DNA showed heterogeneous mutations ranging from different point mutations to small deletions. Two lymphocyte cell lines (T- and B-cell lines) of one patient presented with the same mutation. For another patient, two different mutations were detected in one natural killer cell line. Therefore, different cell lineages have somatic mutations in PIG-A that lead to PNH. PMID- 7888684 TI - Allogeneic blood stem cell transplantation for refractory leukemia and lymphoma: potential advantage of blood over marrow allografts. AB - Peripheral blood stem cells (PBSCs) have been used rarely for allogeneic transplantation because of concerns regarding graft failure and graft-versus-host disease (GVHD). We evaluated the results of allogeneic PBSC transplantation (allo PBSCT) in 9 patients with refractory leukemia or lymphoma receiving myeloablative therapy followed by allo-PBSCT from an HLA-identical sibling donor. Three patients had relapsed 11 to 21 months after allogeneic bone marrow transplantation (allo-BMT) and underwent allo-PBSCT using the same donor. Six patients received PBSCs as their initial allogeneic transplant. Filgrastim mobilized PBSCs were collected from the donors in 3 to 4 aphereses and cryopreserved. The apheresis collections contained a median nucleated cell count of 16.5 x 10(8)/kg (range, 10.8 to 28.7 x 10(8), 10.7 x 10(6) CD34+ cells/kg (range, 7.5 to 22.5 x 10(6)), and 300.0 x 10(6) CD3+ cells/kg (range, 127.8 to 1,523.2 x 10(6)). The median recovery of CD34+ progenitor cells after freezing, thawing, and washing was 106.4% (range, 36.7% to 132.0%). All patients received filgrastim posttransplant through engraftment, and cyclosporine and methylprednisolone were used for GVHD prophylaxis. Neutrophil recovery to greater than 0.5 x 10(9)/L and greater than 1.0 x 10(9)/L occurred at a median of 9 (range, 8 to 10) and 9 days (range, 8 to 11) posttransplant, respectively, which was similar to historical controls after allo-BMT and granulocyte colony stimulating factor therapy. Platelets recovered to greater than 20 x 10(9)/L and greater than 50 x 10(9)/L at a median of 12 (range, 8 to 25) and 15 days (range, 11 to 59), respectively, which was significantly more rapid than for the controls (P < .01). Donor cell engraftment was documented by cytogenetics, fluorescence in situ hybridization, and/or restriction fragment length polymorphisms with longest follow-up of 283 + days. Three patients developed grade 2 acute GVHD involving only the skin. Three of five evaluable patients show limited chronic GVHD. Cryopreserved, filgrastim-stimulated allogeneic PBSCs may be a suitable alternative to allogeneic marrow for transplantation with the advantage of more rapid platelet recovery. Acute GVHD was minimal despite the infusion of 1 log more CD3 cells than with marrow allografts. Further studies are required to assess long-term risks of chronic GVHD. PMID- 7888685 TI - Lack of correlation between human T-lymphotropic virus type I DNA integration and clinical course of adult T-cell leukemia/lymphoma. PMID- 7888686 TI - Prediction of response to recombinant human erythropoietin (r-HuEPO/epoetin alpha) therapy in cancer patients. PMID- 7888687 TI - Indomethacin treatment causes loss of insulin action in rats: involvement of prostaglandins in the mechanism of insulin action. AB - Glucose tolerance tests in rats showed that after indomethacin treatment plasma insulin levels rose five-fold higher than in untreated controls. Accordingly, the pancreatic islets of indomethacin-treated rats secreted insulin at a threefold higher rate. Glucose tolerance tests additionally showed that indomethacin treatment led to a retarded disposal of the elevated blood glucose. Both effects appear to be caused by an attenuation of the hormone responsiveness for insulin and noradrenaline (alpha-adrenoceptor action) by indomethacin. The following observations support this view: insulin and adrenaline (alpha-adrenoceptor action) lost their ability to lower cyclic adenosine monophosphate (AMP) levels in hepatocytes; the glycogen content of liver and skeletal muscle was reduced by 95% and 65%, respectively; in adipocytes the stimulation of glucose transport by insulin was reduced by 60%. These effects of indomethacin can be reversed by the addition of exogenous prostaglandin E (PGE), as elevated cyclic AMP synthesis was again sensitive to alpha-adrenergic inhibition in the liver. These results indicate a relationship between prostaglandins and insulin action. These effects of indomethacin could result from reduced synthesis of cyclic PIP (prostaglandylinositol cyclic phosphate), a proposed second messenger for insulin and alpha-adrenoceptor action, whose synthesis was decreased by indomethacin treatment and increased by the addition of exogenous PGE. Stimulation of glucose transport by cyclic PIP was unaffected by indomethacin treatment, in contrast to the stimulation by insulin. Inhibition of PGE and cyclic PIP synthesis resulted in a metabolic state comparable to insulin resistance in non-insulin-dependent diabetes mellitus. PMID- 7888689 TI - Effect of transplantation site and culture pretreatment on islet xenograft survival (rat to mouse) in experimental diabetes without immunosuppression of the host. AB - Recently, we reported on indefinite islet graft survival in allotransplantation (rat to rat). This was achievable without the use of any immunosuppression by performing transplantation of culture-pretreated (22 degrees C) islets of Langerhans under the renal capsule (r.c.) of chemically induced diabetic recipients. The aim of this study was to test this successful islet modulation technique in a xenogeneic animal model. Six groups of chemically induced diabetic, inbred, C57BL/6J mice received by transplantation either into the liver via the portal vein (i.po.) or under the renal capsule (r.c.) 300-350 either freshly or culture-pretreated (37 degrees C and 22 degrees C) Lewis rat islets without any immunosuppressive therapy. Histology was performed after rejection or post-transplant normoglycaemia (> 120 days) for evaluation of the graft. Transplantation of freshly isolated islets resulted in 75% graft rejection 17 days after transplantation. Using culture pretreatment at 37 degrees C, we noted 75% graft rejection 31 days after transplantation. In contrast, culture pretreatment at 22 degrees C resulted in a marked prolongation of xenograft survival, 75% graft rejection occurring 58 days after transplantation, and in two cases there was indefinite graft survival (> 120 days). Statistical analysis showed a significant prolongation of xenograft survival after culture pretreatment, with the most beneficial effect appearing after low-temperature culture at 22 degrees C (P < 0.05). Interestingly, xenograft survival was markedly prolonged only using the r.c. approach. Statistical comparison revealed a highly significant prolongation using the r.c. as transplantation site compared with i.po. (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888688 TI - A reassessment of fasting plasma glucose concentrations in population screening for diabetes mellitus in a community of northern European ancestry: the Wadena City Health Study. AB - In current clinical and research practice, the determination of diabetic status depends largely on plasma glucose levels 2 h after the ingestion of a standard 75 g glucose load, the oral glucose tolerance test (OGTT). The OGTT, however, remains inconvenient, not highly reproducible, and costly, especially for large scale studies and population screening tests. Fasting plasma glucose (FPG) determinations are convenient, reliable, and valid measures of glucose intolerance, but the currently prescribed cut-off point of 140 mg/dl (7.8 mM) lacks sensitivity. We evaluated the reliability and validity of fasting plasma glucose (FPG) values compared with other measures of hyperglycemia for a diagnosis of diabetes in a population-based study of carbohydrate metabolism in Wadena, Minnesota, a community of predominantly northern European ancestry. As a part of this effort, a random sample of Wadena adults, stratified by age and gender, plus all known, previously diagnosed diabetics participated in 2 days of baseline testing and were followed prospectively and retested 5 years later. Cross-sectional analyses of baseline data are presented in this article. Diabetic status was ascertained by administering a standard OGTT according to National Diabetes Data Group (NDDG) specifications. Sensitivity and specificity levels obtained when using a FPG cut-off point of 6.4 mM were 95.2% and 97.4%, respectively. In study subjects with no known diagnosis of diabetes, the FPG cut off point of 6.4 mM performed reasonably well with a sensitivity and specificity of 67.7% and 97.4%, respectively. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888690 TI - Effect of the introduction of dietary sucrose on metabolic control in children and adolescents with type I diabetes. AB - The effect of sucrose in the diet of children and adolescents with type I diabetes on long-term metabolic control was studied. For a mean observation period of 83 (range 42-127) days, a diet containing 5% of total calories as refined sugar was recommended to 11 children (group A, mean age 15.0, SD 5.4 years), while another 13 children remained on their usual 'sucrose-free' diet (group B, mean age 16.0, SD 5.7 years). The mean observation period in this group was 77 (41-103) days. All children had a dietary assessment at baseline and at follow up using a 7-day food record. At baseline, sucrose intake as a proportion of total daily calories was similar in the two groups (group A 1.4, SD 1.9% vs group B 2.0, SD 2.3%; P = 0.5). At follow-up, sucrose intake increased significantly in group A (5.1, SD 2.5%; P = 0.0008) but not in group B (2.7, SD 3.3%; P = 0.5). Metabolic control assessed by haemoglobin level (HbA1c) was not different between the groups at baseline (group A 8.5, SD 1.2 vs group B 8.8, SD 1.8%; P = 0.7) nor at follow-up (9.1, SD 1.4 vs 9.0, SD 2.5%; P = 0.9). Within group A, the individual change in HbA1c correlated with the individual change in sucrose intake (r = 0.61, P = 0.05), this correlation being strongly influenced by two individuals with an increase in sucrose consumption substantially exceeding 5%. Percentage intake of protein, carbohydrate and fat did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888691 TI - Asymptomatic coronary artery disease in diabetes: relation to common risk factors, lipoproteins, apoproteins and apo E polymorphism. AB - The risk factors for asymptomatic coronary artery disease (CAD) were examined in 138 diabetic patients. Following non-invasive screening examinations (exercise electrocardiography, dynamic thallium scintigraphy, 24-h electrocardiographic recording), CAD was confirmed angiographically in 21 symptom-free diabetic subjects with an ischaemic finding in at least one of the non-invasive tests. The prevalence of asymptomatic CAD in this cohort of diabetic patients was 21/132 (16%), which may be an underestimation because 6 patients refused angiography. Risk factors (age, diabetes, smoking, hypertension, serum lipoproteins, apoproteins and apo E phenotypes) were analysed according to the presence or absence of CAD. Multivariate logistic stepwise analysis did not show any definite changes of serum lipids, lipoproteins and apoproteins in type 1 (n = 72) and type 2 (n = 66) diabetic patients with or without asymptomatic CAD. The only factors associated with asymptomatic CAD were the duration of diabetes (P < 0.005) and the age of the patient (P < 0.05). These results suggest that in diabetic patients the major risk factor for premature coronary atherosclerosis is diabetes itself. Assessment of other risk factors does not seem to define any subgroup with asymptomatic CAD. PMID- 7888692 TI - Self-monitoring of blood glucose in overweight type 2 diabetic patients. AB - Self-monitoring of blood glucose (SBGM) is widely recommended for both type 1 and type 2 diabetic patients despite the lack of evidence of benefit in glucose control or as an aid in weight loss in type 2 subjects. This study tested the hypothesis that combined use of SMBG and dietary carbohydrate (CHO) counting, using the blood monitoring results to shape dietary CHO quotas, is beneficial in managing type 2 diabetes. Twenty-three overweight (body mass index, BMI 27.5-44 kg/m2) patients aged 40-75 participated in a 28-week behavioral weight control program. Baseline hemoglobin HbA1c ranged between 9.5% and 13.5% (normal range 5.5%-7.7%). Subjects were matched for weight, sex, and HbA1c and assigned to small (4-8 participants) groups which met weekly for 12 weeks and then monthly for 16 weeks. After 8 weeks, the groups were randomized either to continue the behavioral program or to have SMBG and dietary CHO counting. Glucose monitoring was performed 6 times daily (pre- and 2 h postprandially) for the first month, focusing on the meal increment and correlating this to dietary CHO intake. Weight loss was identical in both groups during the year of follow-up. The HbA1c level showed a progressive decline in experimental subjects (P < 0.05), whereas there was no improvement in control subjects. PMID- 7888693 TI - Effects of evening primrose oil treatment on sciatic nerve blood flow and endoneurial oxygen tension in streptozotocin-diabetic rats. AB - Evening primrose oil (EPO) is rich in the omega-6 essential fatty acid component, gamma-linolenic acid. The aim of the investigation was to determine whether EPO treatment prevented a reduction in sciatic nerve perfusion and oxygenation in streptozotocin-diabetic rats. Rats were treated from diabetes induction with 10 g EPO kg-1 day-1. Sciatic blood flow was measured by microelectrode polarography and hydrogen clearance. Diabetes caused 47.7% +/- 3.4% (P < 0.001) and 58.8% +/- 4.8% (P < 0.001) reduction in the nutritive (capillary) and the non-nutritive (large vessel) components of endoneurial blood flow, respectively, which were prevented by EPO. Treatment had no significant effect on nutritive flow in non diabetic rats; however, the rate of non-nutritive flow increased by 97.7% +/- 38.9% (P < 0.01). Sciatic endoneurial oxygen tension was measured by microelectrode polarography. Diabetes resulted in a 44.7% +/- 3.4% reduction in mean oxygen tension (P < 0.001), which was largely (82.3% +/- 10.2%) prevented by EPO treatment (P < 0.001). Thus, EPO prevents impairment of blood flow and endoneurial oxygenation in experimental diabetes. It is likely that this neurovascular action accounts for the beneficial effects of treatment on nerve function in diabetic rats and patients. PMID- 7888694 TI - Islet cell antibodies are associated with beta-cell failure also in obese adult onset diabetic patients. AB - To clarify the utility of islet cell antibodies (ICA) to correctly classify and predict insulin treatment in newly diagnosed diabetic subjects, ICA, body mass index (BMI), glycated hemoglobin (HbA1c), and fasting plasma C-peptide values were evaluated at and 3 years after diagnosis in 233 new, consecutively diagnosed, adult diabetic patients classified as obese or nonobese (National Diabetes Data Group, NDDG criteria). Among the 233 patients, 31 were nonobese ICA positive (mean age at diagnosis 43 +/- 3 years), 55 nonobese ICA-negative (mean age at diagnosis 58 +/- 2 years), 7 obese ICA-positive (mean age at diagnosis 57 +/- 5 years), and 139 obese ICA-negative (mean age at diagnosis 58 +/- 1 years). Fasting C-peptide decreased (P < 0.05) in nonobese ICA-positive patients who after 3 years showed lower BMI (22.6 +/- 0.6 versus 24.5 +/- 0.4; P < 0.05), lower fasting C-peptide (0.14 +/- 0.06 nmol/l versus 0.71 +/- 0.07 nmol/l; P < 0.001), and higher frequency of insulin treatment [28/31 (90%) versus 6/45 (13%); P < 0.001] than nonobese ICA-negative patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888696 TI - Blood levels of alloxan in children with insulin-dependent diabetes mellitus. AB - Alloxan is a well-known and universally used agent for evoking experimental diabetes through its toxic effect on the B cells of the Langerhans islets. In our study, blood levels of alloxan in children with insulin-dependent diabetes mellitus were investigated. The observations were made in 68 children aged 6-15 years and in a control group of 44 healthy children in the same age range. Alloxan levels were estimated spectrophotometrically. The mean level of alloxan in blood from children with insulin-dependent diabetes mellitus was 8.76 +/- 9.64 micrograms/ml and in blood from healthy children was 1.53 +/- 1.10 micrograms/ml. The difference was statistically significant (P < 0.05). The metabolism of alloxan leads to the production of free superoxide radicals which, as is well known, injure cells and cause conditions conducive to the occurrence of diseases from autoimmunity. The results obtained suggest therefore that higher levels of alloxan in diabetic children are of significance in the onset of insulin dependent diabetes mellitus. PMID- 7888695 TI - Islet cell cytoplasmic antibody reactivity in midgestational human fetal pancreas. AB - The reactivity of islet cell cytoplasmic antibodies (ICA)-positive and ICA negative sera of recent onset type 1 diabetic patients was studied in human fetal pancreata of 12-18 weeks' gestation and compared with the reactivity of these sera in adult human control pancreata. The aims of the study were: (1) to observe the presence of ICA staining in human fetal islet cells; (2) to compare endpoint titres (in Juvenile Diabetes Foundation units) of ICA-positive patient sera in fetal pancreata and adult human control pancreata. Ten ICA-positive sera and eight ICA-negative sera from newly diagnosed diabetic patients and four sera from healthy controls were tested on three human adult and eight human fetal pancreata. As in the adult control pancreata. ICA-positive sera reacted to insulin-, glucagon-, and somatostatin-positive cells of fetal pancreata of all gestational ages. This was observed both in single cells and in cells in islet like cell clusters. Dilution of a reference serum gave similar results in both adult and fetal pancreata. In contrast, the ICA-positive patient sera yielded a striking heterogeneity in fetal as well as in adult pancreata. However, end-point titres between adult and fetal pancreata did not differ significantly (P > 0.05). In conclusion, ICA-positive sera from recent onset diabetic patients show that the expression of molecules to which ICA react is present in all islet cells and starts before week 12 of gestation. PMID- 7888697 TI - Variant forms of glucokinase gene in Japanese patients with late-onset type 2 diabetes. AB - We have applied the technique of single-strand conformation polymorphism analysis to detect mutations of the glucokinase gene in 50 Japanese patients with late onset type 2 diabetes and in 50 normal Japanese subjects. Out of the 50 patients with late-onset type 2 diabetes, we observed three kinds of variant patterns: one in exon 1b, one in exon 4, and one in exon 5. The incidence of these patterns was one in exon 1b, two in exon 4 and one in exon 5. Direct sequencing of exon 1b and exon 5 revealed mutations in intron areas at the 12th nucleotide downstream from the 5' splice points in two cases. Direct sequencing of exon 4 revealed a heterozygous silent mutation, CCC[Pro]-->CCG[Pro] at codon 145. In contrast, 50 normal Japanese subjects showed no variant patterns in any exons. Our results showed that although 8% (4 out of 50) of Japanese patients with late-onset type 2 diabetes have variant forms of the glucokinase gene, none is expected to cause apparent qualitative changes in glucokinase. We think that the frequency of mutations of the glucokinase gene which could cause qualitative change is very low in Japanese patients with late-onset type 2 diabetes. PMID- 7888698 TI - Cisplatin and carboplatin mediated release of cytolytic factors in murine peritoneal macrophages in vitro. AB - The anticancer drugs cisplatin and carboplatin have been shown to activate murine peritoneal macrophages in vivo and in vitro. These activated macrophages have enhanced tumoricidal activity mediated by extension and contact formation with the tumor cells leading to an increase and transfer of lysosomes with eventual lysis of the tumor cells. Cisplatin (10 micrograms/ml) or carboplatin (50 micrograms/ml) for 2 and 24 h treatment of macrophages in vitro, in addition, show a significant increase in the release of various cytolytic factors, like hydrogen peroxide, superoxide anion, interleukin-1 alpha, lysozyme and beta-N hexoseaminidase, that are also responsible for the destruction of tumor cells. PMID- 7888699 TI - P-glycoprotein overexpression in mouse cells does not correlate with resistance to N-benzyladriamycin-14-valerate (AD 198). AB - The novel anthracycline N-benzyladriamycin-14-valerate (AD 198) circumvents P glycoprotein (P-gp)- and altered topoisomerase II-mediated drug resistance. Nevertheless, AD 198-resistant (AD 198R) murine J774.2 cells overexpressed P-gp, were cross-resistant to other drugs through reduced accumulation and were rendered sensitive by continuous exposure to verapamil. Intracellular AD 198 was, however, similar in sensitive and resistant cells. Consequently, the ability of P gp to confer AD 198 resistance was examined. It was observed that (i) AD 198 resistance in AD 198R cells grown without drug for 15 months declined by 60% with only a 10-15% loss of vinblastine cross-resistance and P-gp expression; (ii) a cloned AD 198R P388 mouse leukemic cell line did not express P-gp; and (iii) verapamil did not attenuate resistance against high-dose, short-term exposure to AD 198. Therefore, AD 198 resistance appeared to be P-gp-independent despite P-gp overexpression. Antioxidant enzyme and topoisomerase II activities remained unchanged between sensitive and resistance cells. These results suggest that AD 198 resistance was conferred by a novel mechanism. PMID- 7888700 TI - Evaluation of antitumor activity of navelbine (vinorelbine ditartrate) against human breast carcinoma xenografts based on its pharmacokinetics in nude mice. AB - The in vitro antitumor activity of navelbine (NVB, KW-2307), a newly synthesized vinca alkaloid, was compared with that of adriamycin (ADM) against human breast carcinomas inoculated into nude mice at the maximum tolerated dose (MTD) and clinically equivalent dose (CED). The plasma levels of NVB after intravenous injection into nude mice at doses of 1.2 and 4.8 mg/kg diminished rapidly during the early phase (0-1 h), followed by a very long shallow one. NVB was still detected 96 h after administration at a dose of 4.8 mg/kg. The pharmacokinetic parameters of NVB in plasma indicated that NVB extensively distributes to tissues. The CED of NVB was provisionally decided to be 4.8 mg/kg based on the comparison of AUC values at 24-infinity h between human patients and nude mice. When compared by a single injection of MTD (NVB, 16 mg/kg; ADM 12 mg/kg), NVB was effective against all four tumor lines, MC-2, MC-8, MMKY and H-31, while ADM was effective only against H-31. On the other hand, the body weight loss by NVB was mild as compared with that by ADM, indicating that the antitumor activity of NVB is superior to that of ADM at their MTDs. A single injection of NVB at its CED (4.8 mg/kg) produced a poor antitumor effect and no or little toxicity in terms of body weight loss, as compared with those at MTD. However, when NVB was administered intermittently at CED, it exhibited significant antitumor activity against three tumor lines. The body weight loss was still mild even on this intermittent schedule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888701 TI - Inhibition by Guan-mu-tong (Caulis aristolochiae manshuriensis) of the growth of spontaneous mammary tumors in SHN virgin mice. AB - Multiparous SHN mice with spontaneous mammary tumors (5-10 mm in size) were given water extract of Guan-mu-tong (Gmt; Caulis aristolochiae manshuriensis) (0.5%) ad libitum as drinking water for 10 days. This treatment retarded significantly the growth of mammary tumors compared with the controls. By contrast, normal mammary gland growth, histology of adrenals and ovaries, and body weight were affected little by the Gmt treatment. Gmt appears to be the first agent inhibiting the growth of spontaneous mouse mammary tumors of palpable size by per os treatment. PMID- 7888702 TI - Topoisomerase I gene expression and cell sensitivity to camptothecin in human cell lines of different tumor types. AB - Topoisomerase I (topo I) gene expression and cell sensitivity to camptothecin were investigated in seven human cancer cell lines not selected in vitro for drug resistance. The cell lines were of different tumor origin, and included two ovarian carcinomas (A2780 and IGROV-1), a cervix squamous cell carcinoma (A431), an osteosarcoma (U2-OS), a glioblastoma (GBM) and two different clones of a malignant melanoma (665/2/60 and 665/2/21). Topo I gene expression was evaluated by Northern blotting analysis and cell sensitivity to camptothecin was determined using the colony-forming assay after a 1 h exposure to the drug. A wide range of drug sensitivity levels was found among the examined cell lines. Cell doubling times and distribution in cell cycle phases were not correlated with camptothecin cytotoxicity. In particular, the percent of untreated cells in S phase was not predictive of the drug sensitivity. No correlation was found between level of topo I gene expression and cell response to camptothecin. These results indicate that the level of topo I expression is not the only critical determinant of cell sensitivity to camptothecin in unselected human cancer cell lines. Therefore, topo I gene expression may not be a useful predictive parameter of tumor response. PMID- 7888703 TI - Anal submucosal injection: methotrexate concentration in rectal tumor tissue and serum after anal compared with parenteral injection. AB - As the results of adjuvant chemotherapy in the treatment of advanced rectal cancer are unsatisfactory, more effective regimens and routes of administration are being tried. Submucosal anal injection of methotrexate (MXT) has given encouraging results in the treatment of pelvic malignancies. This communication studies the MXT level in serum and rectal cancer tissue after either anal submucosal or parenteral MXT administration. Twenty four patients, mean age 46.4 years (16 men and eight women), with stage C rectal cancer were divided into two equal, age- and sex-matched groups. MXT (50 mg) was administered to each patient intravenously in one group and into the anal submucosa in the other. A blood sample was taken 30, 60 and 120 min after injection, and again after 24 h. A tumor sample was also taken each 30 and 60 min of injection. The serum and tissue MXT levels were determined using a radioimmunoassay kit. The serum MXT concentration was significantly higher after parenteral than after anal injection. Meanwhile, the concentration of MXT in tumor tissue was higher after anal administration. In conclusion, the anal route of administration of MXT, by inducing a high MXT concentration in the tumor tissue associated with a low serum level, might achieve satisfactory therapeutic results in advanced rectal cancer, with minimal side effects. PMID- 7888704 TI - Chemotherapy-related persistent indirect hyperbilirubinemia. AB - In spite of the improvement on chemotherapy results in treating testicular cancer and the introduction of adjuvant chemotherapy to node negative (as well as node positive) breast cancer patients, there is still present a wide spectrum of early and late toxic manifestations. The combination of cisplatin, vinblastine and bleomycin given to testicular cancer might result in cariovascular, neurological, gastrointestinal and renal problems. Late effects of cyclophosphamide, methotrexate and 5-fluorouracil given to breast cancer patients might cause obesity, amenorrhea and infertility. We report a persistent asymptomatic indirect hyperbilirubinemia which was observed in two cancer patients (breast; testis) 3 and 14 months following the cessation of chemotherapy. Metastatic liver disease and involvement of other sites, as well as other causes of hyperbilirubinemia, were excluded. The exact cause of the indirect hyperbilirubinemia remained obscure. PMID- 7888705 TI - Electrospray mass spectrometry for the characterization of the purity of natural and modified oligodeoxynucleotides. AB - Electrospray ionization mass spectrometry is an accurate and sensitive analytical method to characterize the purity of oligodeoxynucleotides being tested for pharmacological studies. We report the preparation procedure ('desalting') of natural and modified oligodeoxynucleotides (ODNs) and their analysis by negative ion electrospray mass spectrometry. We evaluate the sensitivity and the accuracy of the method for two antisense ODN sequences. Mass analysis of the 25-mer phosphorothioate can be performed to within 0.001% accuracy (standard error of 0.05 Da) for a sample concentration of 12 pmol/microL. In addition, the adduct ion and the failure sequence can be identified to characterize the antisense ODN. PMID- 7888706 TI - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry of DNA-Pt(II) complexes. AB - Matrix-assisted laser desorption ionization (MALDI) time-of-flight mass spectrometry has been used to characterize the reaction products of the 18-mer deoxyribonucleotide d(AACGGTTAACCGTTAATT) with [Pt(NH3)3(H2O)]2+ and cis [Pt(NH3)2(H2O)2]2+. Characteristic peaks corresponding to different monofunctional adducts (18-mer+n[Pt(NH3)3]) (n = 1, 2, 3 and 4) have been observed with the triamino-monoaqua complex. With the diamino-diaqua cis-Pt complex, formation of a chelate (18-mer+[Pt(NH3)2]) involving two adjacent guanines has been demonstrated. A good correlation between MALDI and polyacrylamide gel electrophoresis results is observed. PMID- 7888707 TI - Sequencing of hydrophobic peptides as lithiated adducts using liquid secondary ion mass spectrometry without tandem mass spectrometry. AB - Lithium cationized hydrophobic peptides in the molecular weight range 1900-2650 Da have been studied by liquid secondary-ion mass spectrometry. The mass spectra exhibit characteristic lithiated sequence ions. N-terminal [a(n)+Li-H]+ and [dn+Li-H]+ ions together with limited C-terminal [ypro+Li+H]+ ions lead to an easy sequencing of the peptides studied, without the need for tandem mass spectrometry. PMID- 7888708 TI - Evaluation of glycosylation site heterogeneity and selective identification of glycopeptides in proteolytic digests of bovine alpha 1-acid glycoprotein by mass spectrometry. AB - Glycosylation sites in bovine alpha 1-acid glycoprotein (AGP) have been identified, and the inherent heterogeneity evaluated, by capillary electrophoretic and reversed-phase liquid chromatography/electrospray-mass spectrometric analyses of proteolytic digests of this glycoprotein. The success of these methods in locating glycopeptides relied on significant heterogeneity within each glycosylation site. In order to rapidly locate sites in glycoproteins of any degree of heterogeneity, a novel mass spectrometric method was applied to selectively identify the glycopeptides in a proteolytic digest of bovine alpha 1 AGP. The glycopeptides were selectively located by the generation and detection of characteristic oxonium ions from the carbohydrate moieties by collision induced dissociation (CID) during liquid chromatography/electrospray-tandem mass spectrometry, and liquid chromatography/CID mass spectrometry, in which fragmentation was induced in the supersonic expansion region of the electrospray source. PMID- 7888709 TI - Utility of organic bases for improved electrospray mass spectrometry of oligonucleotides. AB - The sensitivity and accuracy of the mass spectrometric analysis of oligonucleotides using electrospray ionization can be compromised when the oligomer is adducted in the gas phase to cations such as sodium or potassium. We have evaluated the addition of mM concentrations of a series of organic bases with solution pKb values ranging from 11.5 to 5.5 and gas-phase proton affinities ranging from 213 to 232 kcal/mol as a method for suppression of signals from alkali-adducted ions. Stronger bases such as triethylamine and piperidine reduce the signals from bound sodium most effectively, but also decrease the total ion current from oligonucleotide. Imidazole, with a solution pH of approximately 8.0, provides modest suppression of sodium/potassium adduct ions, but up to a four fold improvement in sensitivity. Co-addition of imidazole and triethylamine or piperidine produces high ion abundance and good suppression of cation-adducted species for samples of phosphodiester or phosphorothioate oligomers which have not been desalted via preliminary precipitation or by high-performance liquid chromatography. Addition of high concentrations of imidazole generates a bimodal distribution of charge states, which may reflect different gas-phase conformations for single-stranded oligomers. PMID- 7888710 TI - Synthetic peptides as binding-step based catalytic mimics. AB - Peptides able to adopt an environment-dependent secondary structure represent attractive models for enzyme mimics. An approach to design new synthetic enzyme like peptides involves the use of binding-step based mimics. The polypeptide melittin, based on its intrinsic ability to bind to phospholipids, was selected as a potential binding-step based catalytic mimic. Synthetic melittin was found to exhibit weak but reproducible phospholipase-like activity. The rate enhancement of the hydrolysis of phospholipids, although far from that of the natural enzyme, was encouraging as a first step in the development of new catalytic peptides. PMID- 7888711 TI - Rapid control of peptide coupling and labeling reaction products with MALDI, time of-flight mass spectrometry. PMID- 7888712 TI - Synthesis of combinatorial libraries with only one representation of each structure. AB - A technique of generating libraries in which every compound is displayed only once and all possible combinations are prepared with absolute certainty is presented. The method is based on the stepwise division of a continuous carrier in each step of randomization. Polypropylene membrane and cotton thread were evaluated as potential supports for this approach to library construction. Cotton thread accommodates 400 nmol of test compound per cm, but its mechanical properties limit the dimension of libraries. An alternative combinatorial library of "restructurable toothbrushes" is suggested. PMID- 7888713 TI - Cyclic peptide template combinatorial libraries: synthesis and identification of chymotrypsin inhibitors. AB - A cyclic peptide template combinatorial library in a positional scanning format, composed of three positional libraries, was synthesized using solid-phase chemistry and four orthogonal protecting groups (Fmoc, Boc, Dde, OAll). The cyclic peptide template is composed of three lysine residues and one glutamic acid residue. The chemical diversity was introduced by acylating the epsilon amino groups of the lysine residues using 10 carboxylic acids in addition to the 20 proteinogenic amino acids. The library components have been shown to be stable towards proteolytic degradation. Compounds with chymotrypsin inhibitory activity were identified through the screening of this library. PMID- 7888714 TI - High yield, directed immobilization of a peptide-ligand onto a beaded cellulose support. AB - Aminopropyl derivatized Perloza beaded cellulose was acylated with alpha bromoacetic anhydride to give alpha-bromo-acetamidopropyl Perloza. (N-Acetyl)-Cys Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2, the 7 C-terminal amino acids of the decapeptide luteinizing hormone-releasing hormone with a cysteine added to the N-terminus, was synthesized using Fmoc chemistry. The purified peptide (1.35-1.9 eq) was coupled to alpha-bromoacetamidopropyl Perloza in 0.1 M NaHCO3 solution, pH 8.3, for 1-2 hours. The peptide was anchored to the support via a thioether linkage. Analysis of the peptide-Perloza conjugate indicated near-quantitative displacement of support-bound bromine by the peptide. The peptidic affinity matrix was able to bind ovine antibodies to luteinizing hormone-releasing hormone (LHRH). Thioether immobilization offers directed, chemically stable, high-yield anchoring of synthetic peptides onto a chromatographic support. The high reaction efficiency means there is little waste of valuable synthetic peptide. PMID- 7888715 TI - Synthesis of an N-3-guanidinopropylglycine (Narg) derivative as a versatile building block for solid-phase peptide and peptoid synthesis. AB - N-(2,2,5,7,8-Pentamethylchroman-6-sulfonyl)-N'-3- (N-9-fluorenylmethoxycarbonyl glycinyl)propylguanidine (1) was prepared and utilized as an arginine surrogate (Narg) building block compatible with solid-phase synthesis according to the Fmoc methodology. Narg is potentially useful in the assembly of combinatorial compound libraries or in the preparation of modified peptides. The applicability of this building block was demonstrated by its incorporation into an analogue of Thr-Arg Ser-Ala-Trp, a pentapeptide for which inhibition of osteoclastic bone resorption was claimed. The modified pentapeptide showed an increased proteolytic stability when compared to the original inhibitor. PMID- 7888716 TI - [The behavior modifying influence of malpractice--effects on choice of technology]. AB - This article analyses the legal concepts of the professional indemnity of the physician in respect of damage caused by him due to fault or negligence, underlining the problem of legal uncertainty connected therewith. Pointers to the possible financial risk involved are given in a review dealing with the probability of damage, costs that may be incurred by such damage, and professional indemnity insurance premiums. Attention is then directed at the influence these factors can exercise on the behaviour and attitude of the physician in respect of performance of medical services and care and on the choice of treatment methods. The defensive type of medical care and the therapeutic gap are mentioned as examples of such changes. PMID- 7888717 TI - [Analysis of trends in infant mortality with special reference to perinatal mortality in Austria (1965-1991)]. AB - In Austria a marked decrease of perinatal mortality has been observed since the middle of the 1970s (Fig. 1). Regression models show a significant association with introduction of the mother-and-child health passport in 1974 and decreasing fertility of women older than 35 years. In part this decrease is due to a transfer of deaths from the perinatal period to later periods (Fig. 3). Some perinatal deaths were shifted to the periods of 2nd to 4th week and 2nd to 12th month after birth, respectively. From the difference between expected and observed perinatal mortality a saving of 13,400 perinatal deaths since 1974 has been calculated. Some of these children were in fact saved from death, whereas some of them died during a later period of the first year of life. PMID- 7888718 TI - [Case studies of sudden infant death cases (SIDS)]. AB - Parents and attending physicians of 100 SIDS victims were interviewed applying a questionnaire especially designed for this purpose. Particular attention was focussed on the courses of pregnancy and birth, medical check-ups and the infants' unusual behaviour during the last days of their lives. As far as possible we compared our data with the results of the Rhenian Perinatal Survey 1990. PMID- 7888719 TI - [Incidence of Lyme borreliosis in Mecklenburg-Vorpommern]. AB - In 1992/93 6202 ticks (Ixodes ricinus) were tested in Mecklenburg-Vorpommern for Borrelia burgdorferi via dark-field microscopy. The prevalence of infected ticks was 7.8%. The sera of 1182 forest workers in Mecklenburg-Vorpommern were tested for antibodies against Borrelia burgdorferi. In 31.4% antibodies to B. burgdorferi were found in the sera of forest workers. PMID- 7888720 TI - [An editorial on the contribution by O. Wassermann and H. Kruse: "Public health risk caused by emissions from refuse incinerators". Refuse incinerators in urban areas (pro and contra)]. PMID- 7888721 TI - [Public health risk caused by emissions from refuse incinerators]. AB - An irresponsible "approval on request" in favour of waste incineration written by a consulting committee of the German Federal Board of Physicians has meanwhile been widely distributed both nationally and internationally. The aim of this politically motivated paper is to dramatically increase the present number of 49 waste incinerators in Germany. It is our duty to warn of this intention. Health problems are known to exist both in workers at waste incinerators and in humans living in their vicinity. Furthermore, in the long run negative impact also to ecosystems should be expected from the emissions. Health problems in patients living downwind of waste incinerators repeatedly have been reported on by physicians. "Lack of statistical significance", often used as counter-argument, is only due to absence of funding of comprehensive epidemiological studies in Germany. Analyses of soil samples reveal the pollution from waste incineration. Considering the pre-load of the region, additional emissions caused by waste incineration and other sources have to be assessed. The application of preventive limit values is imperative. The presently used "limit values", being about 100 times too high, bear an unacceptable risk. Therefore, reliable regional registers of emissions have to be established immediately. Limit values continuously have to be adjusted to the progress of scientific knowledge. In this respect it is imperative to consider that the actual composition of emissions is unknown; isolated risk assessment of single compounds underestimates the total risk; the negative impact, e.g. of dioxins, on both the immune and hormone systems occurs at concentrations 100 times lower than those causing carcinogenic effects; the assumption of "threshold values" is obsolete; a considerable lack of knowledge exists about accumulation in food webs and in ecosystems; the demand of preservation of natural, geogenic situations is indispensable in assessments of soil and water pollution. Essential prerequisites for risk assessments of emissions from waste incineration are 1. actual, continual and comprehensive qualitative and quantitative analytical knowledge of the composition of emissions; 2. region-specific meteorologic dispersion models of the emissions; 3. evaluation of the complex mixtures in emissions for their kinetics in and toxicity for ecosystems and humans. Neither of these demands is so far fulfilled. Facing these problems, the present propagation of waste incineration must be stopped. As an alternative, efforts to optimize waste-avoiding and recycling concepts considerably have to be reinforced, and low-risk procedures, like compost and other decomposing methods, hydrogenation or freeze-griding of plastics, have to be widely promoted. PMID- 7888722 TI - [Substitution treatment of drug-dependent patients]. AB - The author discusses the network of acts of parliament, subordinate legislation and decisions of the courts. Even if a substitution is legal, this does not necessarily mean that the expenses are covered by the statutory medical insurances. While in certain cases the insurances bear the costs of a treatment with methadone, the expenses for codeine and dihydrocodeine can be covered in no case. But it is possible to prescribe both at the expense of the patient. According to the law and the opinions of leading experts it is obligatory that the distribution of substitutes be combined with further medical, psychological and social care. For the latter the insurances cannot be charged. The essay concludes with presumptions about the future development of the regulations in force. PMID- 7888723 TI - [Educational possibilities for personnel in the area of health education in primary school--teacher education--dental health as a didactic topic]. PMID- 7888724 TI - [The need for long-term continuation of AIDS prevention]. PMID- 7888725 TI - [Model project of section 275a SGBV for assessing the need for hospital treatment and implementation in Schleswig-Holstein]. AB - The structural Health Care Law (GSG) of the Federal Republic of Germany provides in section 275a, Volume V of the Social Legislation Code (SGB), for a model project to assess the necessity of hospital admittances. To facilitate a comparison on a national level it is intended that in each Federal state one hospital from each of the different levels of provision, which are established regionally by each state, should be included in the model project. In Schleswig Holstein all admissions to the departments of internal medicine and surgery of the participating hospitals-over 2 periods of 3 weeks in both 1994 and 1995-will be examined retrospectively on the basis of the medical records, this examination being carried out by specialist physicians from the Medizinischer Dienst der Krankenversicherung-MDK (Medical Service of the Health Insurance Funds). The data required is presently collected in three parts: The first part includes all the structural and associated data of the catchment area of each particular hospital. The second part collects all relevant data on patients, this data being rendered anonymous and collected using software specially developed by a national team of the MDK. The third part of the examination of data requires a specialist evaluation of the necessity of each recorded hospital admittance to be made by the specialist physician of the MDK. The results of each part are being evaluated by the MDK Schleswig-Holstein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888726 TI - Comparison of standard chromatographic procedures for the optimal purification of soluble human brain acetylcholinesterase. AB - With the view of purifying soluble human brain acetylcholinesterase (AChE) into its separate isoforms, various preparative chromatographic procedures were compared. Chromatofocusing of cerebrospinal fluid (CSF) AChE revealed two major activity peaks, whilst that of caudate nucleus AChE showed one major peak. Both CSF and caudate nucleus AChE eluted at isoelectric points (pI) of between 5.5 and 5.2. Chromatofocusing failed to separate AChE into its individual isoforms, based on qualitative isoelectric focusing. Preparative purification by affinity chromatography showed a better AChE yield with the use of procainamide as a ligand, vis-a-vis acridinium. Maximum recovery for CSF and caudate nucleus AChE was 10 and 43% using acridinium and procainamide, respectively. Qualitative analysis by SDS-PAGE of affinity-purified AChE revealed four major bands between 50 and 62 kDa, corresponding to the catalytic subunits of AChE as verified by an anti-AChE polyclonal antibody. A size-exclusion column also allowed brain AChE purification, with the latter eluting at a putative molecular mass of 310 kDa. Unfortunately, cation-exchange using the state-of-the-art SMART system failed to separate AChE into its isoforms. AChE aggregation is given as one major obstacle precluding good resolution of isoforms. PMID- 7888727 TI - Interaction of carboxymethyl-gamma-cyclodextrin with anticancer drugs studied by charge-transfer thin-layer chromatography. AB - The interaction between 22 anticancer drugs and carboxymethyl-gamma-cyclodextrin (CM-gamma-CD) was studied by reversed-phase charge-transfer thin-layer chromatography and the relative strength of interaction was calculated. CM-gamma CD formed inclusion complexes with 11 compounds, the complex always being more hydrophilic than the uncomplexed drug. The inclusion forming capacity of drugs differed considerably according to their chemical structure. Both principal component analysis and cluster analysis found a relationship between the inclusion complex forming capacity and hydrophobicity parameters of anticancer drugs. This result suggests that the preponderant role of hydrophobic interactions is in inclusion complex formation. PMID- 7888728 TI - Determination of chloral hydrate and its metabolites (trichloroethanol and trichloracetic acid) in human plasma and urine using electron capture gas chromatography. AB - Capillary gas chromatography with electron capture detection is described for the quantification of chloral hydrate (CH) and is metabolites trichloroethanol (TCE) and trichloroacetic acid (TCA) in 0.1-1 mL of plasma samples. The method, with 2,2'-dichloroethanol (DCE) as internal standard, involved extraction of chloral hydrate and trichloroethanol with diethyl ether and methylation of trichloroacetic acid with 3-methyl-1-tolyltriazene (MTT), followed by diethyl ether extraction. The method has a detection limit of 5 ng/mL for CH and TCE and 10 ng/mL for TCA and also allows the determination of TCE-glucuronide in 0.1-1 mL of plasma samples. It exhibits good linearity and precision. The method was applied to samples of plasma from a neonate after a single dose of 40 mg/kg of chloral hydrate and from an adult after a single dose of 6.25 mg/kg. PMID- 7888729 TI - Determination of fluvoxamine concentration in plasma by reversed-phase liquid chromatography. AB - Fluvoxamine, a serotonin re-uptake inhibitor, was quantified in plasma by modifying a previously published procedure for monitoring plasma concentrations of tricyclic antidepressants. Alkalinized plasma samples were extracted with n hexane/isoamyl alcohol, followed by back-extraction with diluted phosphoric acid. The extracts were analysed by reversed-phase liquid chromatography using a C-18 column, with phosphate/acetonitrile as the mobile phase. The assay was linear from 10 to 800 micrograms/L. Precision studies showed within-run and day-to-day coefficients of variation to be 4.5 and 6.8%, respectively. Desipramine interfered with the detection of fluvoxamine. The assay was used to measure a total of 8 plasma samples from 4 alcohol-dependent patients medicated with fluvoxamine as an adjunct to relapse prevention psychotherapy. In these patients, the plasma concentrations ranged from 54 to 241 micrograms/L. Dosage of fluvoxamine, duration of treatment, interval between last dosage and blood collection were associated with effects on plasma concentrations that were consistent with the pharmacokinetic profile of fluvoxamine. PMID- 7888730 TI - Direct determination of free phenylacetic acid in human plasma and urine by column-switching high performance liquid chromatography with fluorescence detection. AB - A simple and highly sensitive column-switching high performance liquid chromatographic method with fluorescence detection for the determination of free phenylacetic acid (PAA) in human plasma and urine is described. The method is based on the direct derivatization of plasma and urine PAA with 6,7-dimethoxy-1 methyl-2(1H)-quinoxalinone-3-propionylcarboxylic acid hydrazide (DMEQ-hydrazide). The derivatization reaction proceeds in aqueous solution in the presence of pyridine and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide at 37 degrees C. The resulting DMEQ derivative of PAA is separated from endogenous interfering substances by a column-switching chromatographic system consisting of a precolumn (YMC-Pack C4) for sample clean-up and an analytical column (L-Column ODS) for the complete separation of the derivative. The derivative is detected fluorimetrically at 445 nm with excitation at 367 nm. The detection limits (signal to noise ratio = 3) for PAA is 10 fmol in a 10 microL injection volume. The recoveries from plasma and urine are 75 and 96%, respectively. The present method is highly sensitive and simple compared to conventional liquid-liquid extraction procedures. The sensitivity allows the direct determination of free PAA in an extremely small amount (5 microL) of plasma and urine. PMID- 7888731 TI - A quantitative analytical method for the determination of a new anxiolytic (CGS 19480A) in human plasma using high performance liquid chromatography. AB - A sensitive and specific analytical method has been developed for the determination of a new anxiolytic (CGS 19480A) in human plasma using high performance liquid chromatography (HPLC). The drug and internal standard (CGS 18102A), were extracted with hexane at pH 7. Separations were achieved by reversed phase chromatography on a Nucleosil 5 C18 column at a flow rate of 1.0 mL/min. The mobile phase consisted of acetonitrile: 0.01 M phosphate buffer (pH 7): methanol (51:35:14, v:v:v), where the final pH of the mobile phase was adjusted to 4.0 using 85% phosphoric acid. Plasma standard curves were linear from 5.0 to 500 ng/ml, with recovery of the drug being greater than 95% at all concentrations. The method was validated over a concentration range of 5.0 to 500 ng/mL with a limit of quantification of 5.0 ng/mL. The method was successfully applied to the analysis of clinical samples from a single-dose safety and tolerability study conducted in six healthy male volunteers. PMID- 7888732 TI - High-resolution separation of PCR product and gene diagnosis by capillary gel electrophoresis. AB - High-resolution separation of a PCR product from a mixture of DNA restriction fragments was achieved using capillary gel electrophoresis. The capillary gel electrophoretic separation gives an excellent resolution of two fragments of the 500-bp PCR product and the 506-bp DNA fragment, which differs by only 6 bp, and the complete separation of a broader chain length range of DNA afragments up to 12 kbp within 20 min. The plate number of gel-filled capillary was achieved to be 2 million plates per meter. Capillary gel electrophoresis is applied to the gene diagnosis for heart disease through apolipoprotein E genotyping. The advantages and limitations of capillary gel electrophoresis in the application to PCR analysis and DNA diagnosis are discussed. PMID- 7888733 TI - Simultaneous determination of p-aminobenzoic acid and its metabolites in urine by high performance liquid chromatography. AB - We developed a new HPLC method for the determination of p-aminobenzoic acid (PABA) and its metabolites (p-aminohippuric acid, N-acetyl-p-aminohippuric acid, N-acetyl-p-aminobenzoic acid) in urine. As the internal standard m-hydroxybenzoic acid was used. In the isocratic elution the mobile phase consisted of methanol and 0.02 M ammonium acetate (20:80 v/v, pH 4.0). The separation was carried out on the C18, reversed-phase column, particle size 5 microns. The separated components were detected at 280 nm. The method can be used in the assessment of the response of pancrease (secretion of digestive enzymes) to soya feeding as well as in the diagnosis of the exocrine pancreatic diseases of animals. PMID- 7888734 TI - High performance liquid chromatographic analysis of polypeptide hormones in transplanted rat islets. AB - This report describes high performance liquid chromatographic analysis of transplanted pancreatic islets. A reversed phase ODS column made it possible to measure rat insulin I, II, rat C-peptide I, II and glucagon simultaneously in isolated rat islets without using radioisotopes. Freshly isolated islets contained 118.0 +/- 9.7 ng (mean +/- SE, n = 6) insulin and 3.01 +/- 0.60 ng glucagon per islet. The insulin I/II ratio was 1.22 +/- 0.03. Isolated islets were then cultured in vitro or transplanted into mice under the renal capsule. Transplantation induced mild hypoglycemia in the recipients. The graft mean survival time was 7.2 +/- 0.4 days (n = 5). Both cultured (n = 7) and transplanted (n = 6) islets showed similar alterations of polypeptide hormones on day 4. Insulin decreased to one third and glucagon remained unchanged. The insulin I/II ratio increased twofold. In conclusion, it was suggested that the general fate of isolated islets was caused by ischemia and denervation. Relatively, ischemia may not damage alpha cells but may damage beta cells because alpha cells are peripherally located. Denervation may release beta cells from a resting state under neural tonic inhibition. Mild hypoglycemia and an increased insulin I/II ratio were related to the accelerated insulin synthesis in the isolated islets. PMID- 7888735 TI - Determination of glutathione in biological samples by high performance liquid chromatography with fluorescence detection. AB - A selective and sensitive high performance liquid chromatographic (HPLC) method has been developed for the determination of reduced glutathione (GSH) in biological samples (rat liver, spleen and plasma). The method involved a prechromatographic thiol derivatization with methyl 4-(6-methoxynaphthalen-2-yl) 4-oxo-2-butenoate; the reaction was rapid (5 min) under mild conditions (pH 7.5 and ambient temperature) and selective for the sulphydryl group. The thiol adducts were separated on a reversed-phase C-18 column using acetonitrile: 0.05 M triethylammonium (TEA) phosphate (pH 4) solution 32:68 (v/v) as the mobile phase. Fluorescence detection (lambda em = 450 nm; lambda exc = 310 nm) was used and the detection limit (S/N = 3) was about 0.5 pmole of the injected GSH adduct. The method was also applied to the determination of total glutathione in rat plasma after a preliminary reduction with dithiothreitol. PMID- 7888736 TI - Solid phase extraction and high performance liquid chromatographic determination of dobutamine in plasma of dialysed patients. AB - An isocratic reversed-phase high performance liquid chromatographic method has been developed for th e determination of dobutamine in the plasma of dialysed patients. A solid phase extraction method with a Sep-Pak C18 cartridge was used to isolate the drug and isoxsuprine (internal standard) from plasma. The separation was carried out on an ODS-Hypersil column with 0.1 M phosphate buffer:acetonitrile:methanol (72:20:8 v/v/v) as the mobile phase. The recovery of dobutamine added to plasma by the extraction procedure was 87 +/- 2.3% (mean +/- SD). The accuracy and reproducibility of the method were within acceptable limits over the concentration range 0-1000 ng/mL. Quantification was by fluorescence detection at 275 nm excitation and 310 nm emission wavelengths with a detection limit of 5 ng/mL for dobutamine. This procedure was applied to ascertain the pharmacokinetics of dobutamine infusion in nine patients with cardiogenic shock and end-stage renal disease undergoing haemodialysis. PMID- 7888737 TI - Simple determination of formaldehyde in dimedone adduct form in biological samples by high performance liquid chromatography. AB - A high performance liquid chromatographic method for the determination of endogenous formaldehyde in dimedone adduct form in biological samples is described. The simple procedure involves extraction of the formaldehyde of different binding force in biological samples with methanol containing dimedone as the capture molecule and separation on a C18 reversed phase column with methanol as eluent. PMID- 7888738 TI - TLC studies on certain aminoglycoside antibiotics. AB - Aminoglycoside antibiotics were separated by thin layer chromatography. Separation was achieved on untreated silica gel layers using various combinations of solvent systems, dioxane:ammonia, methanol:ammonia and propanol:ammonia. These antibiotics were visualized with the help of iodine vapours. PMID- 7888739 TI - Optical purity determination of thyroxine enantiomers in bulk materials by chiral thin layer chromatography. AB - L-thyroxine and D-thyroxine were separated on ligand exchange chiral thin layer chromatographic plates, using a solvent system consisting of acetonitrile:methanol:water 60:15:15 v/v, at a wavelength of 254 nm. The methodology, chiral recognition mechanism(s) involved and its application are discussed. PMID- 7888740 TI - Head-up tilt, lower body negative pressure, pacemakers and vasovagal syncope. PMID- 7888741 TI - Cardiac pacing does not improve orthostatic tolerance in patients with vasovagal syncope. AB - This study was undertaken to assess the value of dual chamber pacing in the treatment of vasovagal syncope. In a preliminary study, on two patients the time to presyncope during head-up tilt before and after implanting pacemakers was determined. Both patients fainted with similar decreases in blood pressure at almost exactly the same time after tilting. In the main study, nine patients with pacemakers implanted as treatment for syncope were studied, in random order, with pacemakers on and either off or turned to minimum rate. The pacemakers prevented bradycardia but had no effect on the time to syncope in a progressive test of head-up tilt followed by the addition of graded lower body suction. It is concluded that cardiac pacing does not prevent or even delay the onset of postural syncope and infer that bradycardia is an unimportant component of vasovagal attacks. PMID- 7888742 TI - Orthostatic tolerance in patients with unexplained syncope. AB - Orthostatic tolerance in 79 patients complaining of attacks of unexplained syncope, was assessed as the time to imminent syncope in a test involving: head up tilt by 60 degrees for 20 min, followed by tilt and lower body suction at -20 and -40 mmHg for 10 min at each. Blood pressure and heart rate were determined noninvasively. Ninety-five per cent of patients developed signs of presyncope during the test. After 10 min of lower body suction at -20 mmHg, presyncope had occurred in 85% of the patients compared with only 23% in a recently reported group of asymptomatic controls. Both patients and controls were divided into four groups: men and women, under and over 50 years, and the times at which each group of control subjects showed a 20% incidence of syncope were taken as the limits of normality. By those times, overall 85% of patients had developed syncope. It is concluded that the new combined test is able to discriminate patients who have poor orthostatic tolerance and is likely to be of value in assessing the effects of treatment regimes. PMID- 7888743 TI - Power spectrum analysis of heart rate variations in the early detection of diabetic autonomic neuropathy. AB - Power spectrum analysis of the R-R interval was used in 20 controls and in two groups of type I (insulin dependent) diabetics (27 patients) to detect changes in total power or in its components (low frequency and high frequency) that might be considered an early evidence of impairment of cardiac autonomic nervous system control. A significant difference between controls and severe diabetics (with autonomic involvement) was found in all components. In the early stage of diabetes without evidence of autonomic involvement, an absolute reduction of the low frequency component in the standing position and a significant reduction of the percentage increase compared with the lying position, was found to discriminate diabetics from controls. The occurrence of somatic neuropathy was unrelated to changes in autonomic function. These data indicate that: (1) power spectrum analysis is sensitive enough to detect cardiac autonomic neuropathy in diabetics, where standard methods fail; (2) power spectrum analysis is the method of choice in the early stages; (3) in severe type I dependent diabetes there is a reduction of power spectrum analysis total power and a defective response to standing up; (4) cardiac autonomic neuropathy develops independently from somatic neuropathy. PMID- 7888744 TI - Alterations in cardiac muscarinic acetylcholine receptors in mice with autoimmune myocarditis and association with circulating muscarinic receptor-related autoantibodies. AB - Hearts from mice hyperimmunized with cardiac tissue were studied to evaluate the expression and biological activity of muscarinic cholinergic receptors and immunoglobulin G deposits along the immunization period. Mice were sacrificed at 10 day intervals from the first injection up to day 100. Simultaneously, the activity of autoantibodies against muscarinic receptors on normal hearts was also examined in sera. Hearts with autoimmune myocarditis showed a muscarinic receptor related dysfunction, with an impaired response to exogenous muscarinic agonists and a significant reduction in muscarinic binding sites, both effects being maximum at 40-50 days post-immunization. In addition, serum or immunoglobulin G from mice with myocarditis were able to interact with muscarinic acetylcholine receptors displaying a partial agonist effect. Autoimmune sera and immunoglobulin G reduced heart contractility while inhibited 3H-QNB binding to cardiac acetylcholine receptors in a concentration dependent manner showing the highest effects at days 40-50 and decreased progressively thereafter. The development of muscarinic receptor-related cardiac dysfunction may be associated with the presence of circulating antibodies having muscarinic receptor activity. These studies are of relevance to clinical conditions such as Chagas' disease, where immunological processes involving the cholinergic system are considered to cause cardiomyopathy. PMID- 7888745 TI - Reflex cutaneous vasoconstriction during cold pressor test is mediated through alpha-adrenoceptors. AB - The effects of the cold pressor test on the coronary circulation have been clearly defined but the effects on the peripheral vasculature are less well understood. To measure the peripheral vasomotor response during cold pressor test perfusion in the upper extremity contralateral to the cold immersion was assessed by laser Doppler flowmetry and skin-surface temperature gradients. To identify the mechanism of vasoconstriction, cold pressor test was performed before and after the administration of phentolamine, an alpha-adrenoceptor antagonist. Vasoconstriction during cold pressor test was demonstrated by both skin-surface temperature gradients and by laser Doppler flowmetry. This vasoconstrictor response was significantly attenuated by the administration of phentolamine. The results demonstrate that the cold pressor test induces an alpha-adrenoceptor mediated vasoconstriction in the peripheral vasculature. PMID- 7888746 TI - Cerebellar lesions alter autonomic responses to transient isovolaemic changes in arterial pressure in anaesthetized cats. AB - In previous studies, bilateral lesions of the rostral fastigial nucleus (rFN) of the cerebellum impaired recovery of mean arterial pressure (MAP) after many forms of hypotension. This study examined effects of cerebellar lesions on baroreflex responses during transient, isovolaemic, non-orthostatic changes in MAP in anaesthetized cats. Bilateral rFN lesions did not alter the rate or extent of fall in MAP induced by nitroprusside, but reduced by 39% the reflex increase in heart rate per unit decrease in pressure (delta HR/delta MAP). Femoral artery resistance remained below control levels. Lesions prolonged the time for 50% MAP recovery after nitroprusside by 93%. During phenylephrine-induced MAP increases, bilateral rFN lesions augmented reflex delta HR/delta MAP by 68%. In intact cats, the reflex decrease in HR after phenylephrine was blocked by electrical stimulation of the rFN, but appeared immediately after stimulation was stopped. Stimulation alone increased both MAP and HR. Propranolol failed to block either the increased HR or the suppression of reflex cardiodeceleration induced by rFN stimulation. Decreases in resting HR after rFN lesions may reflect removal of tonic cerebellar inhibition of cardiac parasympathetic tone. Thus, the cerebellum can influence autonomic output and modify baroreflex sensitivity by augmenting cardiovascular responses mediated by the sympathetic nervous system and inhibiting those mediated by the parasympathetic nervous system. PMID- 7888748 TI - A palaeontological perspective. AB - Palaeontology and molecular biology researchers need to develop a better dialogue. The recovery of biological information from Precambrian ecosystems that are thousands of millions of years old, the search for radical genomic reorganizations that might explain the irruption of groups with novel body plans, and the recovery of diagnostic molecules from fossils are all areas of active research, but communication between disciplines does not always occur. PMID- 7888747 TI - Sweating and vascular responses in the face: normal regulation and dysfunction in migraine, cluster headache and harlequin syndrome. AB - At least four neural mechanisms influence facial blood flow. Firstly, sympathetic vasoconstrictor fibres exert a tonic constrictor influence on the vasculature of the ears, lips and nose, and sparsely supply other parts of the face. Secondly, the sympathetic nervous system actively dilates the cutaneous vasculature of the face during heat stress and emotion. Thirdly, parasympathetic vasodilator reflexes in the facial and glossopharyngeal nerves increase blood flow to the exocrine glands and tissues of the eyes, nose and mouth when these tissues are irritated. Fourthly, axon reflexes release vasoactive peptides from sensory fibres, which participate in local inflammatory responses. The sympathetic nervous system normally controls facial sweating. However, after injury to postganglionic sympathetic fibres, parasympathetic fibres sometimes make functional connections with sweat glands, so that parasympathetic reflexes provoke pathological sweating. In this review, new information about the neural pathways and stimuli which influence facial sweating and blood flow is summarized, and this is followed by a discussion of the pathophysiology of extracranial vascular disturbances and facial sweating in migraine, cluster headache and harlequin syndrome. PMID- 7888749 TI - Very old DNA. AB - The verification of DNA sequences obtained from very old tissue sources as indeed ancient is a major point of discussion in the ancient DNA field. Proper controls and the use of the phylogenetic approach are the general methods employed for verification of the ancient DNA. Most studies have reported the recovery of extremely small amounts of nucleic acids which are sheared into rather small fragments. In addition, problems such as 'PCR jumping' can produce spurious sequence information. These observations suggest that random amplification techniques and the development of primers for highly informative but short target regions are essential for the further development of the ancient DNA field. PMID- 7888750 TI - Archaebacterial genomes: eubacterial form and eukaryotic content. AB - Since the recognition of the uniqueness and coherence of the archaebacteria (sometimes called Archaea), our perception of their role in early evolution has been modified repeatedly. The deluge of sequence data and rapidly improving molecular systematic methods have combined with a better understanding of archaebacterial molecular biology to describe a group that in some ways appears to be very similar to the eubacteria, though in others is more like the eukaryotes. The structure and contents of archaebacterial genomes are examined here, with an eye to their meaning in terms of the evolution of cell structure and function. PMID- 7888751 TI - Introns: evolution and function. AB - The debate continues on the issue of whether nuclear introns were present in eukaryotic protein-coding genes from the beginning (introns-early) or invaded them later in evolution (introns-late). Recent studies concerning the location of introns with respect to gene and protein structure have been interpreted as providing strong support for both positions, but the weight of argument is clearly moving in favour of the latter. Consistent with this, there is now good evidence that introns can function as transposable elements, and that nuclear introns derived from self-splicing group II introns, which then evolved in partnership with the spliceosome. This was only made possible by the separation of transcription and translation. If introns did colonize eukaryotic genes after their divergence from prokaryotes, the original question as to the evolutionary forces that have seen these sequences flourish in the higher organisms, and their significance in eukaryotic biology, is again thrown open. I suggest that introns, once established in eukaryotic genomes, might have explored new genetic space and acquired functions which provided a positive pressure for their expansion. I further suggest that there are now two types of information produced by eukaryotic genes--mRNA and iRNA--and that this was a critical step in the development of multicellular organisms. PMID- 7888752 TI - Simple sequences. AB - Simple sequences (or microsatellites) are stretches of monotonous repetitions of short (1-5bp) nucleotide motifs that are distributed across the whole genome in eukaryotes. They are probably generated by slippage during replication and their primary mutation rate seems to be controlled predominantly by the efficiency of the mismatch repair system. Although most mutations in simple sequence loci appear to be neutral, some mutations in particular stretches have been implicated as having a role in human genetic diseases. PMID- 7888753 TI - Plant transposable elements and the genome. AB - Transposable elements are ubiquitous in the plant kingdom and share many common features, both structural and mechanistic, with mobile elements from other eukaryotes. Transposition of these elements can influence plant genes and genomes in many ways. It is also becoming clear that transposable element derived sequences can be a major component of plant genomes. These sequences are probably, therefore, very significant factors in plant evolution. PMID- 7888754 TI - The ends and the middle: putting chromosomes together. AB - The three known classes of eukaryotic telomeres share the requirement for an RNA template in their replication. This RNA-templated replication is subject to species-specific differences, such as telomere length and its regulation, which suggest that telomeres may have acquired different additional functions in different organisms. Centromeres show less conservation than do telomeres. PMID- 7888755 TI - Codon usage and genome evolution. AB - The rates and patterns of evolution at silent sites in codons reveal much about the basic features of molecular evolution. Recent increases in the amount of sequence data available for various species and more precise knowledge of the chromosomal locations of those sequences, coming in particular from genome projects, reveal that some features of molecular evolution vary around the genome. PMID- 7888756 TI - Comparative genome mapping in mammals. AB - The mammals all have similar amounts of DNA, usually distributed over 40-60 chromosomes. Most of the differences in karyotype are related to fixation of less than 100 reciprocal translocations which have occurred over less than 100 million years. This allows the genome mapping of the main laboratory and farmyard species to help, and to be helped by, mapping of the human genome. PMID- 7888757 TI - Mapping in plants: progress and prospects. AB - Comprehensive genetic maps are now available for all of the world's important crop species. Data show a remarkable conservation of order of markers over family wide taxonomic groupings and illuminate species relationships and mechanisms of genome evolution. Comparison of genetic and physical maps has revealed differences in genetic distance throughout genomes with implications for genome organization, gene isolation and transformation. PMID- 7888758 TI - The evolution of mitochondrial DNA. AB - Although the massive sequencing of mitochondrial DNA from various organisms, together with studies of a different nature, has contributed enormously to the knowledge of the organization and function of this cytoplasmic genome, many issues, mainly the relationships with the nuclear genome, remain unsolved. This review critically evaluates the most recent advances in research on the evolution of the mitochondrial DNA from a qualitative and quantitative point of view, underlining the multiplicity of structures and genetic organization of this genome, which contrasts with its reduced, but rather constant, information content in various organisms. It also highlights the role that mitochondrial DNA is now playing, particularly in metazoans, in different disciplines and application fields. Among these, particular attention is focused on the discovery of the mitochondrial origin of several diseases affecting primarily the neuromuscular system. PMID- 7888759 TI - Investigating sea turtle migration using DNA markers. AB - The past year has seen a further marshaling of genetic evidence for 'natal homing' in several species of marine turtles, a phenomenon wherein females, upon reaching sexual maturity, exhibit a propensity to return to nest at or near the respective beaches upon which they hatched some two or more decades earlier. This genetics-based inference stems from the strong spatial patterning observed in mitochondrial DNA lineages among nesting sites. Rookery-specific mitochondrial DNA markers are now being employed to monitor the natal sources of individuals captured at other phases of the life cycle, and the genetic findings have important conservation ramifications. PMID- 7888760 TI - Ancient origin of RNA editing in kinetoplastid protozoa. AB - A rooted phylogenetic tree of the kinetoplastid protozoa has been constructed that, together with a comparative analysis of editing of several genes, leads to the surprising conclusion that extensive or pan-editing with multiple overlapping guide RNAs is more ancient than 5'-editing. The mechanism of editing is still uncertain, but multiple ribonucleoprotein complexes have been identified that contain components of the enzymatic machinery. PMID- 7888762 TI - Genomes and evolution. PMID- 7888761 TI - Biased (A-->I) hypermutation of animal RNA virus genomes. AB - RNA genomes evolve largely on the basis of single point mutations introduced by imprecise RNA polymerases, or by recombination. Clusters of certain transitions (biased hypermutations) were detected first in the genomes of persistent viruses, and in the past year have also been found in the genomes of lytic RNA viruses. A cellular RNA-modifying enzyme probably introduces the clustered transitions and thus contributes to the evolution of RNA viruses. PMID- 7888763 TI - Learning and representation in speech and language. AB - Infants learn language with remarkable speed. By the end of their second year they speak in sentences with an 'accent' typical of a native speaker. How does an individual acquire a specific language? While acknowledging the biological preparation for language, this review focuses on the effects of early language experience on infants' perceptual and perceptual-motor systems. The data show that by the time infants begin to master the higher levels of language--sound meaning correspondences, contrastive phonology, and grammatical rules--their perceptual and perceptual-motor systems are already tuned to a specific language. The consequences of this are described in a developmental theory at the phonetic level that holds promise for higher levels of language. PMID- 7888764 TI - Speech motor control. AB - The development of new measurement techniques and improved models of the larynx and the vocal tract have significantly advanced our understanding of speech motor control. Recently, several groups have been using electromagnetic transduction techniques to record tongue movements. The laryngeal vibrations have been modeled and studied using techniques from non-linear dynamics. Computational models of supraglottal movements have been proposed and tested. A connectionist model that synthesizes the results obtained from observing the effects of variations in rate, stress, and phonetic context on speech kinematics has recently been proposed. PMID- 7888765 TI - Pattern generation in birdsong. AB - The temporal pattern of birdsong derives largely from the timing of activity in the bird's respiratory muscles. Birds can simultaneously produce two different temporal patterns from the left and right halves of their vocal organ. Recent studies using lesions, neurophysiological recordings, and electrical perturbation of neural signaling in song nuclei are beginning to elucidate the central mechanisms of song pattern generation. PMID- 7888766 TI - Functional imaging of the motor system. AB - Recent studies of the motor system using functional imaging have served to emphasize the complexity of the control of even relatively simple movements. The results of these studies suggest that the behavioral context of the movement is an important determinant of functional activation within cortical motor areas. PMID- 7888767 TI - Distributed motor processing in cerebral cortex. AB - Responding to a visual cue requires processing throughout many areas in the brain. The anatomical pathways connecting these diffuse areas are numerous. One way to study the cognitive processing associated with volitional movement is to identify common physiological properties in each area. Recently, the discovery that neuronal activity is broadly tuned in many of these cortical areas has led to new insights into the physiological structure of the process underlying cognition in this distributed system. PMID- 7888768 TI - Parietal control of hand action. AB - Recent advances suggest that neurons of the anterior intraparietal area play a critical role in the visual guidance of hand action. The parietal cortex appears to process in-coming binocular visual signals of the three-dimensional features of objects and matches these signals with the motor signals, which come from the ventral premotor cortex, that will be required for hand manipulation of the object. PMID- 7888769 TI - Superior colliculus cell types and models of saccade generation. AB - Recent experiments on the cat and monkey have revealed several different cell types within the superior colliculus, including fixation, burst, and build up cells. During primate saccades, activity remains fixed at one location in burst cells, but spreads across the colliculus in build up cells. New models based on the activity of these cell types suggest their functional roles in saccade generation. PMID- 7888770 TI - Oculomotor control: Listing's law and all that. AB - Previously, eye positions were characterized by the direction of sight, which has two degrees of freedom for conjugate movements and three degrees of freedom for vergent movements. Several groups have recently presented reliable data and unconventional models on binocular coordination, where all three degrees of freedom for one or both eyes have been taken into account. The results illustrate Bernstein's principle that in order to simplify control, the brain establishes unique relations between the target and motor space, in which non-Euclidean geometry of rotations is observed. PMID- 7888771 TI - Neural control of feeding. AB - Substantial progress has been made in identifying the possible signals for initiating and terminating the appetitive aspects of feeding behavior in vertebrates. Strong evidence now implicates ATP (or an ATP-like molecule) and a fall in glucose in initiating feeding. In invertebrates, particular progress has been made in defining the nature and mechanisms of action of the neurotransmitters and peptide co-transmitters that regulate the consummatory aspects of feeding, and a number of new research tools for modelling the operation of simple feeding motor program networks have been developed. PMID- 7888772 TI - Postural control system. AB - The postural control system has two main functions: first, to build up posture against gravity and ensure that balance is maintained; and second, to fix the orientation and position of the segments that serve as a reference frame for perception and action with respect to the external world. This dual function of postural control is based on four components: reference values, such as orientation of body segments and position of the center of gravity (an internal representation of the body or postural body scheme); multisensory inputs regulating orientation and stabilization of body segments; and flexible postural reactions or anticipations for balance recovery after disturbance, or postural stabilization during voluntary movement. The recent data related to the organization of this system will be discussed in normal subjects (during ontogenesis), the elderly and in patients with relevant deficits. PMID- 7888773 TI - Reinforcement learning control. AB - Reinforcement learning refers to improving performance through trial-and-error. Despite recent progress in developing artificial learning systems, including new learning methods for artificial neural networks, most of these systems learn under the tutelage of a knowledgeable 'teacher' able to tell them how to respond to a set of training stimuli. Learning under these conditions is not adequate, however, when it is costly, or even impossible, to obtain this kind of training information. Reinforcement learning is attracting increasing attention in computer science and engineering because it can be used by autonomous systems to learn from their experiences instead of from knowledgeable teachers, and it is attracting attention in computational neuroscience because it is consonant with biological principles. Recent research has improved the efficiency of reinforcement learning and has provided some striking examples of its capabilities. PMID- 7888774 TI - Spinal pattern generation. AB - Recent research in the field of spinal pattern generation has concentrated on three main areas: the effects of various transmitters on spinal rhythmic patterns in reduced preparations (neonatal rats, chick embryos, tadpole embryos, lampreys); the changes in membrane properties of different elements of the generating circuits; and the interactions between central generating mechanisms and afferent inputs. The important message is that new properties of neural membranes, as well as new reflex responses, have been identified that could not have been predicted in the absence of such rhythmic activity. PMID- 7888775 TI - Neuronal network models of motor generation and control. AB - Computer simulation of neuronal networks is rapidly becoming accepted as a powerful tool in neuroscience. We illustrate the trends in this field by looking at motor generation and control, with examples from recent modeling studies of different systems, including the spinal swimming rhythm generator of the lamprey. PMID- 7888776 TI - Presynaptic control of neurones in pattern-generating networks. AB - Recent studies have revealed presynaptic influences on neurones that participate in rhythmic motor patterns. Although there is still little direct information about the effects of these inputs at presynaptic terminals, their functional consequences are being unraveled. These presynaptic influences gate sensory input to pattern-generating networks and locally alter the synaptic strength and/or the activity pattern of network neurones. PMID- 7888777 TI - Dopaminergic regulation of striatal efferent pathways. AB - In the past year there has been a growing debate about the distribution of dopamine receptors in striatal efferent pathways. As is often the case, different approaches lead to different perspectives. Nevertheless, the available data can be reconciled with a model in which D1 and D2 dopamine receptors are segregated in the distal dendrites and axonal terminal fields of striatonigral and striatopallidal neurons, but intermingled in the soma and proximal dendrites. PMID- 7888778 TI - Control of prosthetic gait. AB - Recent advances in two types of prosthetic gait are particularly noteworthy, namely work on limb and neural prostheses. Current work on artificial limbs has been oriented towards improving devices, with commercialization as the driving force. Progress has been made in understanding how the compliant properties of the foot, ankle and knee joints of artificial legs affect the energetics and kinematics of gait. Work is continuing on automated systems for fabricating sockets with improved fit to increase the comfort of artificial limbs. Neural prostheses use electrical stimulation to activate paralyzed muscle. Advances have been made in understanding how to model the patterns of neural prosthetic gait and how neural prostheses respond to disturbances. Work in real-time control of stimulated muscle has progressed in the area of system identification and in using natural sensors for feedback signals. There still remains a wide gap, however, between able-bodied gait and the gait that can be achieved using current neural prosthesis systems. PMID- 7888779 TI - Neural control. PMID- 7888780 TI - Immunoregulatory properties of IL-13: its potential role in atopic disease. AB - IL-13 is a relatively novel cytokine produced by activated T cells. IL-13 inhibits the production of proinflammatory cytokines and chemokines by activated monocytes, induces B cell proliferation and differentiation, including IgE production, and the expression of certain adhesion molecules on endothelial cells. All these biological properties of IL-13 are shared with IL-4, but in contrast to IL-4, IL-13 does not act on T cells. In this review, the similarities in structure and biological function of IL-13 and IL-4 and the commonalities of their receptors are summarized. The potential role of IL-13 in allergic responses is briefly discussed. PMID- 7888781 TI - Does amalgam affect the immune system? A controversial issue. AB - Although in use for more than 150 years, dental amalgam has been questioned more or less vigorously as a dental restoration material due to its alleged health hazard. Humans are exposed to mercury and the other main dental amalgam metals (Ag, Sn, Cu, Zn) via vapour, corrosion products in swallowed saliva, and direct absorption into the blood from the oral cavity. Dental amalgam fillings are the most important source of mercury exposure in the general population. Local, and in some instances, systemic hypersensitivity reactions to dental amalgam metals, especially mercury, occur at a low frequency among amalgam bearers. Experimental and clinical data strongly indicate that these and other subclinical systemic adverse immunological reactions to dental amalgam metals in humans will be linked to certain MHC genotypes, and affect only a small number of the exposed individuals. These individuals will be very difficult to detect in a mixed population of susceptible and resistant individuals, including persons with alleged symptoms due to dental amalgam fillings, where many of the individuals are likely to suffer from conditions with no proven immunological background such as multiple chemical sensitivity syndrome. Intensified studies should be performed to identify such susceptible MHC genotypes, taking advantage of the reported cases of more heavily metal-exposed humans with systemic autoimmune reactions. Further studies will also be needed to ascertain whether the combined exposure to the metals in dental amalgam may lower the threshold for adverse immunological reactions, since recent studies have shown that the metals in alloy, especially silver, may induce autoimmunity in genetically susceptible mice. PMID- 7888782 TI - The ocular muscle cell is a target of the immune system in endocrine ophthalmopathy. AB - The exact pathogenic mechanism of thyroid-associated ophthalmopathy (TAO) remains unclear, and extensive studies on this disorder have resulted in often conflicting data. Well-known technical difficulties including the limited access to orbital tissues from patients with active and early disease, lack of an animal model and poor reproducibility of some of the immunological techniques used are in part responsible for this confusing situation. Despite this there is considerable evidence for eye muscle (EM) tissue involvement in the autoimmune reactions of TAO. Although the primary EM antigen(s) recognized by immunocompetent cells and autoantibodies has not been definitely identified, some good candidates, among them a membrane antigen of 64 kD which is also expressed in the thyroid, have been partially characterized. While it is unclear which component of the autoimmune reaction against EM-humoral or cell mediated-plays the more important role, autoantibodies seem to be responsible at least in part for the clinical features of the eye disorder. On the other hand, the orbital connective tissue (OCT) cells, especially the fibroblasts surrounding the EM fibers, seem to be extremely sensitive to stimulation by cytokines and other soluble proteins and immunoglobulins released in the course of an immune reaction in the muscle cells. Fibroblasts secrete large amounts of glycosaminoglycans and also participate in maintaining the autoimmune reaction. It seems likely that the EM is the main and primary target of the orbital autoimmune process whereas inflammation of the OCT is probably secondary. PMID- 7888783 TI - The fibroblast is the target cell in the connective tissue manifestations of Graves' disease. AB - A controversy exists concerning whether the extraocular muscle cell or the fibroblast is the autoimmune target in Graves' ophthalmopathy (GO). Although the extraocular muscle bodies are grossly enlarged in GO, the muscle cells themselves are histologically intact. Within the muscle bodies, as well as in the fatty connective tissue of the orbit, there is an accumulation of glycosaminoglycans (GAG). These hydrophilic mucopolysaccharides are made by fibroblasts. In this commentary, I will present evidence that the fibroblast, and not the extraocular muscle cell, is the autoimmune target in GO and in the other connective tissue manifestations of Graves' disease (pretibial dermopathy and acropachy). This argument is based on clinical evidence, on histochemical and biochemical evidence of fibroblast stimulation in GO, and on functional evidence that patients' orbital lymphocytes recognize autologous orbital fibroblasts, and not eye muscle extract. PMID- 7888784 TI - Immunoregulating effects of peptidoglycan monomer linked with zinc in adult mice. AB - Since it is well known that both zinc ions and bacterial immunostimulants influence the function of the immune system, in the present study we investigated the immunomodulating activity of a new analog of peptidoglycan monomer (PGM), in which the basic molecule was linked to zinc (PGM-Zn). Its effects in BALB/c mice, aged 10-12 months, were compared with the effects of equimolar doses of PGM and ZnCl2. The treatment lasted 26 days (one i.p. injection every fifth day). The results showed that PGM-Zn may markedly enhance antibody production to sheep red blood cells, as well as spontaneous and concanavalin A (ConA)-induced blastogenesis. The generation of plaque-forming cells in individual mouse was positively correlated with the expression of class II antigens in the liver and negatively correlated with the total quantity of hepatic proteins. PGM-Zn also induced the appearance of peritoneal macrophages, which in cocultures with syngeneic splenocytes were less able to enhance the spontaneous, and particularly the ConA-induced blastic transformation. The enhancing activities of PGM-Zn were in some respects more closely correlated with the action of PGM, whereas the induction of suppressive macrophages resembled more the activity of ZnCl2. The data emphasize that PGM-Zn may both stimulate and inhibit immunoregulative pathways by mechanisms which are not identical to those of PGM or ZnCl2. PMID- 7888785 TI - Origin of angiotensin in human leukocytes. AB - The capability of human leukocytes to synthesize angiotensin peptides was studied. Leukocytes which were prepared from heparinized blood by sedimentation in dextran were incubated for 0, 1, 2, 4, 6, 8, and 24 h at 37 degrees C with the 3H-labeled amino acid isoleucine. At the various time points the washed cells were extracted with 0.1 M acetic acid. The extracts contained radioactive material which eluted from a Bio Sil TSK 125 gel filtration column in the low molecular-weight range with the same retention time as synthetic angiotensin I (ANG I) or angiotensin II (ANG II). The extracted radioactive material also bound to anti-ANG I and anti-ANG II antibodies. However, excess of unlabeled synthetic ANG I or ANG II failed to displace the bound radioactivity. Rechromatography of the radioactive material which eluted in the low molecular weight fractions of the gel filtration column could be characterized as non-incorporated 3H isoleucine on a reversed phase C18 column with an acetonitrile gradient. These findings demonstrate the lack of an angiotensin-generating pathway in human leukocytes. Further studies are necessary to determine the origin of angiotensin peptides in human leukocytes. PMID- 7888786 TI - Detection of Epstein-Barr virus and cytomegalovirus genome in white blood cells from patients with juvenile rheumatoid arthritis and childhood systemic lupus erythematosus. AB - The role of infectious agents in the pathogenesis of autoimmune diseases has long been a matter of debate. This study investigated the possible role of Epstein Barr virus (EBV) and human cytomegalovirus (HCMV) infections in the pathogenesis of autoimmune diseases by an attempt to demonstrate the presence of the viral genome in the leukocyte of 21 juvenile rheumatoid arthritis (JRA) patients, 20 childhood-onset systemic lupus erythematosus (SLE) patients, and 20 age-matched normals, using polymerase chain reaction (PCR) and DNA probes. The results showed: (1) there was no difference in serum IgG anti-EBV antibody titers among three groups; (2) the EBV PCR-positive rates for JRA and SLE patients and normal controls were 5% (1/21), 10 (2/20), and 0% (0/20), respectively; (3) the HCMV PCR positive rates for JRA and SLE patients and normal controls were 33% (7/21), 25 (5/20), and 10% (2/20), respectively, and (4) the HCMV-positive rate was 25% for JRA patients with steroid treatment and 33% for those without steroid treatment. It is, therefore, concluded that: (1) the data do not support the participation of EBV and HCMV in the pathogenesis of childhood-onset SLE and JRA; (2) steroid therapy does not increase the frequency of HCMV infection in JRA patients, and (3) immunoincompetence might be one of the major factors contributing to increased susceptibility to HCMV infection in JRA and SLE patients. PMID- 7888787 TI - Purification and partial amino acid sequencing of a 27-kD natural rubber allergen recognized by latex-allergic children with spina bifida. AB - We purified from natural rubber latex (NRL) by means of high-performance liquid chromatography a 27-kD protein, recognized characteristically by IgE in sera from latex-allergic children with spina bifida or other congenital anomalies and histories of multiple surgeries. N-terminal sequence analysis of the purified 27 kD protein was unsuccessful suggesting that its N-terminus is blocked. To obtain internal sequence information from the protein it was digested with trypsin and the purified tryptic peptides were subjected to sequence analysis. Thirteen of the 14 sequenced peptides revealed no significant homology to any of the published protein sequences indicating that the 27-kD protein is previously undescribed at the primary structure level. However, one of the 14 sequenced peptides showed significant homology to the rubber elongation factor, a 14.6-kD NRL protein. For the time being, the 27-kD NRL protein is the first molecularly characterized NRL allergen associated with defined clinical manifestations of latex allergy. PMID- 7888788 TI - Serological evidence of Aspergillus type I hypersensitivity in a subgroup of pulmonary aspergilloma patients. AB - Aspergillus causes a spectrum of diseases, among which aspergilloma (saprophytic colonization) and allergic bronchopulmonary aspergillosis (ABPA). We investigated the possible presence of type I hypersensitivity in patients with aspergilloma (as is classically found in ABPA). The sera of 38 patients with aspergilloma were investigated for the presence of Aspergillus-specific IgE by the CAP System (CAP) and by the RAST System (RAST). Twelve of these patients (32%) showed positive Aspergillus-specific IgE (group ASP-IgE+), with the CAP being more sensitive than the RAST. Median total IgE was higher in the ASP-IgE+ group as compared with the ASP-IgE- f1p4p (p < 0.05), but no differences were seen between the ASP-IgE+ group and patients with ABPA. Furthermore, when Alternaria-specific IgE were compared between ASP-IgE+ and ABPA groups, they were found more frequently in the latter group (p < 0.05). Thus, an aspergilloma group with type I hypersensitivity was isolated whose serologic profile to Aspergillus antigens was similar to the ABPA group. However, the patients in this group did not show sensitization to another mould (i.e., Alternaria), in contrast to the ABPA group. The presence of type I hypersensitivity in a subgroup of aspergillomas suggests an immunoallergic component to this disease which could contribute to a chronic inflammatory response to Aspergillus in some aspergillomas. PMID- 7888789 TI - Occupational allergy to adult chironomid midges among environmental researchers. AB - A case of occupational allergy to chironomid midges in research work is described. A researcher was exposed to adult chironomid midges during his research and developed allergic rhinitis after 10 years of such exposure. Using the midge extract of adult Chironomus plumosus (CP) (Linnaeus, 1758), both immediate skin test and the ophthalmic challenge test gave positive results. IgE antibody against adult CP was also demonstrated by the radioallergosorbent test. Four of the five serum samples of the environmental researcher examined showed a positive radioallergosorbent test to at least one of the adult midges breeding around eutrophic Japanese lakes. Enzyme-linked immunosorbent assay inhibition test and immunoblot experiments indicated that the remaining hemoglobin is one of the major allergens of adult CP. These results demonstrate that the exposure to adult chironomid midges is an important occupational hazard among environmental researchers. PMID- 7888790 TI - Correlations between complaints, inflammatory cells and mediator concentrations in nasal secretions after nasal allergen challenge and during natural allergen exposure. AB - A quantitative determination of the inflammatory mediators was performed and correlated with complaints and the measurement of the inflammatory cells in nasal secretions of 18 seasonal allergic rhinitis patients (group 1) outside the pollen season and 40 symptomatic patients (group 2) with seasonal allergic rhinitis during the pollen season. Ten nonallergic subjects (group 3) were also studied as a normal control group. In group 1, 17 (94%) out of 18 patients had an immediate response of nasal symptoms accompanied by a significant increase of histamine, leukotriene C4 (LTC4), and tryptase 5 min after nasal allergen challenge (NAC). One hour later, a simultaneous increase was seen both in the percentage of the eosinophils and in the eosinophil cationic protein (ECP) concentration. The eosinophil count reached a peak 2 h after NAC with a duration of 8 h, while the highest ECP level was reached only after 24 h with no clear-cut plateau. In group 2, a high percentage of eosinophils was observed. Mostly one observed significantly (p < 0.01) higher concentrations of ECP, LTC4 and histamine but not of tryptase than the baseline values of group 1. The authors concluded that during the pollen season allergic rhinitis reflects mainly a chronic state of allergic inflammation of the nasal mucosa involving various inflammatory components induced by one or more episodes of early-phase type allergic reaction. Infiltration of eosinophils and consequently release of the various late-phase inflammatory mediators into the nasal secretions are certainly believed to be the predominant pathophysiologic condition in the patients. PMID- 7888791 TI - Relationship between nasal resistance and airway hyperreactivity following nasal provocation with Dermatophagoides pteronyssinus in allergic rhinitis. AB - To determine whether nasal allergic symptoms can cause bronchial hyperresponsiveness to methacholine, 30 subjects with allergic rhinitis (22 with allergic rhinitis and 8 with allergic asthmatic rhinitis) were studied. All subjects were skin test positive to Dermatophagoides pteronyssinus (DP) and underwent nasal allergic provocation with DP. After provocation, there was a severe nasal allergic reaction in the challenged nostril with a significant increase in nasal resistance both immediately and long (7 h) after DP exposure. There were no significant changes in the forced expiratory volume in 1 s and the forced expiratory flow rate between 25 and 75% of the forced vital capacity and in both allergic rhinitis and allergic asthmatic rhinitis patients. There was also no change in bronchial hyperresponsiveness to methacholine. The eosinophil counts, leukotriene B4, leukotriene C4 and platelet-activating factor levels in nasal discharges also showed no differences in both groups of patients. Our studies suggest that nasal provocation with limited allergen is a safe diagnostic technique. However, the relationship between nasal resistance and airway hyperreactivity is not obvious in this study. The similar concentrations of nasal inflammatory mediators in both allergic rhinitis and allergic asthmatic rhinitis indicate that bronchial hyperreactivity is not solely due to nasal drainage of inflammatory mediators. PMID- 7888792 TI - Allergen exposure in acute asthma causes the release of platelet-activating factor (PAF) as demonstrated by the desensitization of platelets to PAF. AB - Platelet-activating factor (PAF) is released in IgE-mediated allergic diseases. The normal level, the method of its determination and its clinical importance are subject of controversy. We hypothesized that a functional assay could help to better analyze the actual concentrations in vivo because PAF may be released locally and is short-lived. An assay to detect PAF by the desensitized state of human platelets exposed to PAF in vitro or ex vivo was developed: We analyzed the synergistic platelet response to dual agonist stimulation at extraordinarily low doses (collagen 0.10 microgram/ml and PAF 2.5 x 10(-8) M) in aggregation and release reaction and its absence after previous exposure to PAF at concentrations between 5 x 10(-9) and 5 x 10(-11) M in vitro. The same test was then applied to examine the platelets from patients with IgE-mediated allergic asthma before and after inhalation of the specific allergen (inhalative provocation test; a reduction of the FEV1 by > 15% was considered positive). The lack of a synergistic response to collagen with PAF was found after preincubation of the platelets with 5 x 10(-9) M PAF and a reduction of +/- 50% with 5 x 10(-10) M in vitro. A significant reduction of the aggregation response (-56 +/- 18%) and of the release of beta-thromboglobulin (-75 +/- 24%) was found in 6 patients with a positive inhalative provocation test but not in 3 patients with a negative response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888793 TI - Eosinophil differentiation and hypodensity alteration activities in Dermatophagoides pteronyssinus-stimulated mononuclear cell culture supernatants derived from asthmatics. AB - We investigated the contributing effect of Dermatophagoides pteronyssinus stimulated mononuclear cell (MNC) cultured supernatants on the differentiation and density alteration of eosinophils. MNC, obtained from either normal subjects or asthmatics, were cultured with or without D. pteronyssinus. The supernatants were tested for the activity of eosinophil differentiation and density alteration. The results showed a significant increase in eosinophil differentiation activity in D. pteronyssinus-stimulated MNC supernatants of asthmatics when compared with normal subjects. This activity can be blocked by anti-IL-5 antibodies. Eosinophil hypodensity change was also noted after treatment with D. pteronyssinus-stimulated MNC supernatants or IL-5, but not after D. pteronyssinus treatment. In conclusion, MNCs, activated by D. pteronyssinus, might contribute to the eosinophil differentiation and hypodensity change in asthmatics. PMID- 7888795 TI - The Cooley issues. Dedicated to Denton A. Cooley in recognition of his 50 years of medical practice. PMID- 7888794 TI - Circulating ICAM-1 in alcoholic liver cirrhosis. AB - The intercellular adhesion molecule 1 (ICAM-1) level in the serum of patients with alcoholic liver cirrhosis was measured using a sandwich enzyme-linked immunosorbent assay. Circulating ICAM-1 was significantly elevated in the sera of all 19 patients as compared with normal healthy subjects. There was no correlation with the Child grade of the disease, but the highest levels of serum ICAM-1 (2,416 +/- 560 ng/ml) were measured in those patients who suffered from superimposed acute alcoholic hepatitis. No elevated serum ICAM-1 level was found in the ascitic fluid of cirrhotic patients. The elevated serum levels of ICAM-1 in patients with alcoholic liver diseases may provide useful diagnostic or prognostic information. PMID- 7888796 TI - Some reflections on Denton A. Cooley. PMID- 7888797 TI - Denton, Brock, and I. PMID- 7888798 TI - Denton Cooley's part in the evolution of heart surgery in the years 1944-1994. PMID- 7888799 TI - The fruits of our labors. Particularly Denton Cooley's. PMID- 7888800 TI - Coronary heart disease at altitude. AB - In the past, it has been assumed that some basic physiologic responses to altitude, exposure in coronary patients are comparable to those in normal young subjects. In fact there are similar changes in sympathetic activation, heart rate, and blood pressure early after ascent, with decrements in plasma volume, cardiac output, and stroke volume as acclimatization proceeds. These responses are described, and experience with coronary patients is reviewed. During the 1st 2 to 3 days at altitude, coronary patients are at greatest risk of untoward events. Gradual rather than abrupt ascent, a moderate degree of physical conditioning, early limitation of activity to a level tolerated at low altitude for somewhat less), and attention to blood pressure control all appear to have protective effects. Ascent to moderate altitude appears to entail little risk in coronary patients who are asymptomatic or have moderate exercise tolerance, provided that the above precautions are observed and that activity does not exceed levels at lower altitude. If activity is to be increased, pre-ascent treadmill exercise testing or Holter monitor data secured under conditions comparable to those anticipated at altitude may provide reasonable guidelines. For coronary patients previously evaluated and known to be in a high-risk category, indications for ascent should be examined more critically, and precautionary measures should be more rigorous. Advice for patients with known coronary disease who may desire to trek at very high altitude must involve individual evaluation, and guidelines remain elusive. PMID- 7888801 TI - The cumulative risks of prolapsing mitral valve. 40 years of follow-up. AB - Prolapsing mitral valve is a common cardiac condition, occurring in approximately 16 million people in the United States alone. Primary prolapsing mitral valve may be familial or nonfamilial and may be associated with myxomatous degeneration of the mitral valve leaflets, such as occurs in Marfan syndrome and other connective tissue disorders. Secondary forms may be associated with such entities as rheumatic fever (especially after commissurotomy) and coronary artery disease (in the presence of ruptured chordae tendineae), and with such congenital conditions as interatrial defect and primary cardiomyopathy with outflow tract obstruction. Prolapsing mitral valve is characterized by late systolic murmur, mid-systolic click, or both. Arrhythmias occur in the form of benign premature atrial contraction, premature nodal contraction, and paroxysmal atrial tachycardia. As the patient ages, atrial flutter and atrial fibrillation tend to develop. In some chronic cases, especially those involving atrial fibrillation, systemic emboli may occur. Rare premature ventricular contractions may be largely benign, whereas more frequent premature ventricular contractions may lead to severe arrhythmic complexes such as ventricular tachycardia or ventricular fibrillation. With advancing age, atrioventricular conduction defects of varying degrees or sick sinus syndrome may necessitate a pacemaker installation. About one quarter of prolapsing mitral valve cases progress, with increasing mitral insufficiency and increasing enlargement of the left atrium and left ventricle, which at times leads to congestive heart failure. Coronary artery disease may occur with the severity commensurate with the patient's age group. About three quarters of patients with prolapsing mitral valve syndrome lead normal lives. PMID- 7888802 TI - Tetralogy of Fallot. The first 300 years. AB - The chronicle of tetralogy of Fallot is part of a dramatic evolution in cardiology, cardiac surgery, and understanding of the developing heart. Many new tools and concepts have evolved since Steno of Denmark first described the defect in 1673, and since Fallot of Marseilles coined the term tetralogy in 1888. Four major eras of progress can be recognized. The 1st, the era of pathologic anatomy, culminated in the publication of Maude Abbott's Atlas of Congenital Cardiac Disease in 1936. The next, the era of clinicophysiology and surgery, was highlighted by the 1st Blalock-Taussig anastomosis in 1944, by open-heart surgery 10 years later, and by a new team approach to cardiology. The 3rd, or infant era, began in the mid 1970s with successful intracardiac repair in infants, the rise of echocardiography, and the introduction of prostaglandin therapy. The current era of cardiac development (beginning in the 1990s) gives hope for early understanding of the molecular basis of tetralogy. Tribute is due to the surgical and medical pioneers, and to the pioneer patients and their families, for revolutionary changes in diagnosis and treatment. The challenge of the next 100 years lies in increased understanding of the molecular biology of the defect and in preserving the blend of humanism, scholarship, and skill that have graced the advances of the past 3 centuries. PMID- 7888803 TI - Myocardial revascularization. Historical considerations. PMID- 7888804 TI - Current methods for circulatory support. AB - Although the concept of artificial circulatory support has existed for almost 200 years, it has only been within the last 4 decades that engineers and physicians have developed mechanical devices that can 1) temporarily support the circulation in a patient until the heart recovers or a new heart can be transplanted, or 2) permanently replace a failed heart. In this paper, we briefly describe the devices and techniques that are in current clinical use and speculate on the use of such devices in the future. PMID- 7888805 TI - Pseudoaneurysm of the left ventricle. AB - Pseudoaneurysm of the left ventricle most often occurs after transmural myocardial infarction but may also follow cardiac operations, trauma, inflammation, or infection. In contrast to patients with true ventricular aneurysm, those with false aneurysm most commonly die of hemorrhage. Review of the reported surgical experience and of our 14 cases confirms that standard chest radiographs with an abnormal cardiac silhouette and rapidly expanding size may alert the physician to this sometimes overlooked diagnosis. Noninvasive tests such as color-flow Doppler echocardiography, 2-dimensional echocardiography, cineangiographic computed tomography, and transesophageal echocardiography allow relatively easy recognition of these apparently rare lesions with increasing frequency. Cardiac catheterization, however, is usually still necessary for a clear picture of the location and anatomy of the aneurysm and the state of the coronary arteries. Finally, a new classification is proposed, consisting of true aneurysm, false aneurysm, pseudo-false aneurysm, and mixed aneurysm. PMID- 7888806 TI - High-risk surgery as an alternative to transplantation. AB - Between April 1992 and April 1994, 185 patients were waiting for a cardiac transplant at our institution. Transplantation was performed in 118 of these patients. Twenty-six patients (14%) died while awaiting a donor heart: 13 of these were in the intensive care unit on multiple inotropic medications, mechanical support, or both; another 13 were either in the hospital on a single inotropic medication or at home with or without inotropic support. The remaining 41 patients were still awaiting transplantation at the end of the study period. During the same interval, 20 comparably ill patients who were referred to our institution for transplantation were considered for high-risk conventional surgical procedures. These patients underwent clinical evaluation to determine whether they had viable muscle that was salvageable and electrophysiologic status that was alterable. On this basis, these 20 patients underwent a variety of combined high-risk procedures. Two patients died; the operative mortality was 5% and the cumulative mortality was 10%. We conclude that these initial results support our original impression that mortality rates are higher in patients waiting for cardiac donation than in patients undergoing high-risk surgical procedures. Therefore, we will continue to investigate high-risk conventional surgery as an alternative to cardiac transplantation. PMID- 7888807 TI - Surgical techniques for aortic valvuloplasty. AB - Since 1988, reparative techniques have been used at our institution to treat valvular insufficiency in selected patients with aortic valve disease. The limitations of aortic valve replacement are well recognized; it is this knowledge that has motivated us to find out whether a subgroup of patients who have aortic insufficiency might be candidates for preservation of their native aortic valves. This subgroup includes patients who have leaflet prolapse, perforation, or calcification. We describe our methods of patient evaluation and selection, as well as our surgical techniques for both bicuspid and tricuspid aortic valve repair. PMID- 7888808 TI - Coronary intravascular ultrasound in 2 children after cardiac transplantation. AB - Coronary intravascular ultrasound imaging has been found to be the most sensitive method for detecting postcardiac transplantation coronary vasculopathy. Techniques for this type of imaging have been well established for adult patients, but coronary intravascular ultrasound imaging in young children has not been previously reported. We describe the cases of 2 children, ages 8.5 years and 9 months, respectively, who had confusing clinical pictures after cardiac transplantation. Currently available imaging equipment and techniques were used in these children to visualize the coronary arteries. The results of ultrasound imaging were considered helpful in determining future treatment for these 2 pediatric patients. PMID- 7888809 TI - Massive pulmonary embolism 3 hours after cardiopulmonary bypass. An exceeding rare case. AB - A 70-year-old woman underwent an aortocoronary bypass. Three hours later, she experienced severe pulmonary embolism, diagnosed by transesophageal echocardiography and followed by cardiac arrest. Resuscitation maneuvers were unsuccessful. Autopsy confirmed the diagnosis. When pulmonary embolism occurs after cardiopulmonary bypass for cardiac surgery, it usually occurs in the 2nd postoperative week; and to the best of our knowledge, the literature contains no other reports of cases that occurred during a shorter postoperative interval. Prevention of pulmonary embolism in high-risk patients is mandatory. When embolism occurs, transesophageal echocardiography is an essential tool in making the diagnosis and in guiding the surgeon during intervention. PMID- 7888810 TI - Hypertrophic obstructive cardiomyopathy in combination with anomalous insertion of papillary muscle directly into anterior mitral leaflet and "sawfish" systolic narrowing of the left anterior descending coronary artery. AB - This report describes an unusual case of subaortic stenosis in which hypertrophic obstructive cardiomyopathy was found in combination with both anomalous insertion of papillary muscle directly into the anterior mitral leaflet and "sawfish" systolic narrowing of the left anterior descending coronary artery. Definitive diagnosis was made on operation. We freed the left anterior descending coronary artery by incising the muscular bridge, resected both papillary muscles, and replaced the mitral valve. PMID- 7888811 TI - Mitral stenosis with left atrial thrombus. PMID- 7888812 TI - Primary malignant mesothelioma of the pericardium. PMID- 7888814 TI - So, you want to be an author. Publishing without perishing. PMID- 7888813 TI - Enhancing research through partnerships. PMID- 7888815 TI - Ethics of maternal serum screening. PMID- 7888817 TI - Listening to their stories. Disclosures and the dilemmas. PMID- 7888816 TI - Respecting the rights of gay patients. PMID- 7888818 TI - Radiology rounds. Peduncular colonic polyp, which is a potential precursor of colon cancer. PMID- 7888819 TI - Dermacase. Pigmentation from a junctional nevus in the nail matrix. PMID- 7888820 TI - Agents against pediatric diarrhea. Assessing the information companies supply to Canadian physicians. AB - OBJECTIVE: To assess information on the safety and efficacy of medications that could be used to treat children who have acute infectious diarrhea. DESIGN: Survey of product monographs. Companies were asked to supply their best evidence that products were both safe and effective for treating children who have diarrhea and to supply any information on adverse effects among Canadian children related to use of the products. PARTICIPANTS: Companies making drugs identified in the Compendium of Pharmaceuticals and Specialties as used for acute infectious diarrhea. MAIN OUTCOME MEASURES: Product monographs were reviewed for availability (over-the-counter or by prescription), mention of oral rehydration therapy, age (or weight) limit for use, and safety information. Information in the monographs was compared for completeness with a report from the World Health Organization or the American Medical Association's Drug Evaluations Annual. RESULTS: Four companies market a total of six products. Only one monograph specifically mentioned rehydration therapy. Safety information in two monographs was comparable to that in the WHO report. Safety information in two monographs was limited. None of the companies were able to provide placebo-controlled studies showing their products to be effective. CONCLUSIONS: If these products remain on the Canadian market, companies making them should cease to list them as indicated for acute infectious diarrhea among children. All company-supplied literature should unequivocally state that oral rehydration therapy is the best treatment for this condition. Safety information on some of the products should be upgraded. PMID- 7888821 TI - Teaching residents to use asthma devices. Assessing family residents' skills and a brief intervention. AB - OBJECTIVE: To evaluate an educational program for family medicine residents on using selected inhaler devices for delivery of asthma medications. DESIGN: A prospective analysis using pretests and posttests of a nonrandomized study group and control group. The study group of residents was given an instructional manual and a set of devices for home study, followed by a 1-hour tutorial session with a clinical instructor that included a video and hands-on practice. SETTING: Family medicine centres in Edmonton hospitals. PARTICIPANTS: The study group consisted of a convenience sample of 23 first- and second-year family medicine residents at the Misericordia Hospital Family Medicine Centre. The control group consisted of a convenience sample of 22 first- and second-year family medicine residents at the Royal Alexandra Hospital Family Medicine Centre. Nine residents did not take the posttest; one was absent because of injury, one missed the in-service, and seven had left the city on other rotations, had completed their program, or declined to participate. MAIN OUTCOME MEASURES: Improvements in scores on a multiple-choice test and in techniques of using the devices. RESULTS: Using an average of scores on seven different devices, only 36% of residents showed adequate knowledge of how to use the devices on the pretest. Posttest scores improved for both the control (P < 0.001) and study (P < 0.001) groups, but improvement was significantly greater for the study group (P < 0.001). CONCLUSIONS: Residents lacked adequate knowledge of asthma devices. More study is needed to confirm the long-term effectiveness of formal teaching about the devices. PMID- 7888822 TI - Listening to patients' stories. Storytelling approach in family medicine. AB - This paper discusses the relevance of a storytelling approach for understanding psychological problems in family practice and assesses the value of such an approach. PMID- 7888823 TI - Truth-telling in clinical practice. AB - Disclosure by doctors to patients has changed during the past 30 years in the direction of honesty, but deception and nondisclosure are still common. Clear ethical and legal precedents and guidelines regarding truth-telling exist. Physicians should not protect patients from potentially upsetting information; they will be held responsible should patients be injured due to failure to disclose. PMID- 7888824 TI - Recurrent dermatitis from jellyfish envenomation. AB - Jellyfish envenomation can cause an immediate local skin reaction, which is usually a painful linear vesiculourticarial eruption. Persistent, delayed, or recurrent dermatitis is less common. Because jellyfish sting reactions and their management are unfamiliar to family physicians, we describe a case of recurrent local dermatitis after jellyfish envenomation and suggest appropriate treatment. PMID- 7888825 TI - Guidelines for control of meningococcal disease. Laboratory Centre for Disease Control. PMID- 7888826 TI - Caring for children. PMID- 7888827 TI - Management of hereditary hemochromatosis. AB - Hereditary hemochromatosis is a common disorder of iron metabolism with a prevalence as high as 8 per 1000. Affected individuals absorb excessive amounts of dietary iron and over time, tissue iron deposition results in skin discoloration, arthropathy, hepatic cirrhosis, heart failure, diabetes mellitus and impotence. Early diagnosis and institution of phlebotomy treatments will prevent these manifestations and normalize life expectancy. Once organ damage is established many of the manifestations are irreversible. Since the early manifestations of the disease are subtle, a case can be made for routine screening. This conclusion is supported by cost-effectiveness analysis based on available data. A reasonable screening strategy would start with a serum transferrin saturation. A value > or = 55% should trigger a repeat transferrin saturation in a fasting state and a serum ferritin level. If both these tests are abnormal, a liver biopsy with quantitative iron determination is the currently accepted confirmatory test. PMID- 7888828 TI - Defining the Rh blood group antigens. Biochemistry and molecular genetics. AB - The Rh blood group antigens (D, Cc and Ee series) are carried by a family of non glycosylated hydrophobic transmembrane proteins of 30-32 kDa which are missing from the red cells of rare Rhnull individuals that express several membrane defects. The structure of these proteins has been deduced from cDNA cloning and studies have shown that the Rh proteins are erythroid specific and share no sequence homology with any known protein. The RhD and non-D proteins exhibit 92% sequence identity and their predicted membrane topology is similar as most of the molecules appear to reside between the leaflets of the phospholipid bilayer with only short hydrophilic loops connecting the twelve putative transmembrane helices. The RHD and RHCE genes encoding the Rh proteins (D and Cc/Ee, respectively) are organized in tandem on chromosome 1p34-p36 and most likely derived by duplication of a common ancestral gene. This concept is supported by the identification of RH-like genes in non human primates. The human RH locus is best described as a two-gene model in which all RhD-positive and most RhD negative haplotypes are composed of two (RHD and RHCE) or only one (RHCE) structural genes, respectively. The RHD gene encodes the D protein and the RHCE gene encodes the C/c and E/e proteins presumably by alternative splicing of a pre messenger RNA. The correlation between the blood group D epitopes and the amino acid polymorphism of the Rh proteins is not yet established, but amino acid polymorphisms at positions 103 and 226 determine the molecular basis for the C/c (Ser-->Pro) and E/e (Pro-->Ala) specificities, respectively. Most variants analyzed so far are caused by gene conversion which appears as the principal mechanism responsible for polymorphism and gene diversity in the RH system. However, gene deletions have also been found in some occasions. To date, all Rhnull phenotypes investigated most likely result from transcriptional regulatory mechanisms that are not yet understood. Rhnull individuals suffer a clinical syndrome of varying severity and their red cells are characterized by morphological and functional abnormalities of cation transport and phospholipid asymmetry. In addition, several membrane components including the Rh proteins and other glycoproteins recently characterized (Rh50 glycoprotein, CD47, glycophorin B, Duffy, LW) are absent or severely decreased on these cells. These findings suggest that the Rh proteins are assembled into a multimeric complex with these glycoproteins and further studies should clarify the role in biosynthesis and the potential function of each component in this complex. PMID- 7888829 TI - Current status and future perspectives in the treatment of low-grade non Hodgkin's lymphomas. AB - Low-grade non-Hodgkin lymphomas (NHL) comprise a heterogeneous group of disorders both in terms of their cellular and histological composition as well as in terms of their clinical course. The most usually applied classification systems, the Working Formulation and the Kiel classification as well as the recently proposed Revised European American Lymphoma classification, discriminate between low-, intermediate- and high-grade subtypes. In general, low-grade NHL are characterized by a low to moderate proliferative activity and a long clinical course with median survival times ranging from approximately 3 years for centrocytic (CC) or mantle-cell lymphomas (MCL) to 5-8 years for centroblastic centrocytic (CB-CC) or follicular lymphomas (FL). Recent cytogenetic and molecular biologic analyses indicate that these differences may result from distinct genetic abnormalities such as the translocation t(14;18), which is frequently observed in FL-NHL and is associated with a bcl-2 overexpression and inhibition of apoptosis, or the deregulation of PRAD1 in MCL-NHL induced by the translocation t(11;14). Therapy of low-grade lymphomas depends mainly on the extent of the disease. In the early stages I and II, at which approximately 15 to 20% of low-grade NHL are diagnosed, radiotherapy may be applied with curative intention. The treatment of patients with more advanced stages III and IV is controversial. The currently available information justifies a conservative approach of observing the natural course of the disease until therapeutic intervention is required due to the occurrence of B-symptoms, hematopoietic insufficiency or lymphoma progression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7888830 TI - Treatment of hematological malignancies relapsing after allogeneic bone marrow transplantation. AB - The rate of relapse after allogeneic bone marrow transplantation (BMT) varies between 15 and 60%. New therapeutic strategies are required urgently as no significant results have been obtained with standard chemotherapy. The best results of second allogeneic BMT have been obtained when the interval between the first and the second transplant was more than 6 to 20 months, depending on the study. Veno-occlusive disease was an important cause of non-leukemic death (13 65%). As the toxicity of second BMT is very high, other treatments have been considered: complete remissions were reported after sudden discontinuation of the immunosuppressive therapy. Interferon-alpha has been used for chronic myeloid leukemia patients and may achieve hematological and cytogenetic complete remission. More recently, donor leucocytes transfusions have been proposed and at least in some cases, have led to molecular complete remission (polymerase chain reaction with double amplification) in chronic myeloid leukemia patients. However, non predictable marrow aplasias and graft-versus-host reactions hamper the efficacy of this strategy. Finally, hemopoietic growth factors used to promote donor cell growth produce interesting results which deserve further studies. PMID- 7888831 TI - Intrahepatic cholestasis of pregnancy. PMID- 7888832 TI - Pulmonary emphysema. PMID- 7888833 TI - Making routine data adequate to support clinical audit. PMID- 7888834 TI - Medicine's core values. PMID- 7888835 TI - WHO denounces health benefits of alcohol. PMID- 7888836 TI - Stroke victim's case highlights legal confusion. PMID- 7888837 TI - Conference urges better housing for better health. PMID- 7888838 TI - GMC to revise its ethics advice. PMID- 7888839 TI - Alzheimer's society welcomes Reagan's "bravery". PMID- 7888840 TI - Merck offers money back guarantee on finasteride. PMID- 7888841 TI - France tightens up controls on foreign doctors. PMID- 7888842 TI - Russia proposes testing foreigners for AIDS. PMID- 7888843 TI - Australian surgeons savaged by cutting report. PMID- 7888844 TI - Methods and consequences of changes in use of episiotomy. AB - OBJECTIVES: To evaluate the use of feedback by graphical profiles of rates of episiotomy and the impact on clinical practice and perineal state after spontaneous vaginal deliveries assisted by midwives with different attitudes towards episiotomy. DESIGN: Observation period in labour ward followed by feedback to midwives about their own and other midwives' use of episiotomies. The periods before and after the intervention were compared. SUBJECTS: All women (n = 3919) delivering during the two periods who had been assisted by one of 30 midwives; each midwife supervised at least 20 deliveries during each period. MAIN OUTCOME MEASURES: Overall rates of episiotomies and indications, incidence of intact perineums, perineal lacerations, and tears of anal sphincter. RESULTS: The overall rate of episiotomy during the observation period was 37.1% (615). During the second period the rate was 6.6% lower (95% confidence interval 3.6% to 9.6%), corresponding to a relative decrease of 17.8% (10.1% to 24.7%). Higher rates of episiotomy during the observation period were associated with larger reductions in the second period. The decrease could be explained by less use of episiotomy in deliveries with rigid perineum or impending perineal tear. Compared with the observation period, in the second period 3.2% more women (0.3% to 6.3%) had an intact perineum after delivery and 3.4% (0.4% to 6.2%) experienced perineal tears. The overall incidence of tears of the anal sphincter remained unchanged. Women had a slightly reduced incidence of tears of the anal sphincter, however, if they were delivered by midwives who reduced a medium or high initial rate of episiotomy and a tendency towards an increased incidence of tears if they were assisted by midwives who reduced low initial rates (around 20%) of episiotomy. CONCLUSIONS: Changes in the use of episiotomy induced by awareness of clinical practice among midwives seem to increase the incidence of parturients with intact perineum without a concomitant rise in tears of the anal sphincter. To avoid the increase of such tears these changes should probably be restricted to midwives with rates of episiotomies above 30%. PMID- 7888845 TI - Fetal sex determination in infants in Punjab, India: correlations and implications. AB - OBJECTIVES: To determine the proportion of children whose sex was determined prenatally among those attending one Indian hospital and to identify factors which affect use of fetal sex determination. DESIGN: Cross sectional study using interviews with mothers. SETTING: Medical school hospital in Punjab, India. SUBJECTS: 596 children delivered or seen for inpatient or outpatient care. MAIN OUTCOME MEASURES: Fetal sex determination, sex of child, number and sex of siblings, type of care received, socioeconomic status, and maternal education. RESULTS: Sex had been determined prenatally for fewer girls (5/236, 2%) than boys (49/360, 14%). Fetal sex determination had been done for only 2% (3/154) of first born boys compared with 18% (12/66) with one older sister and no older brother and 63% (30/48) with more than one older sister and no older brother. Only four boys whose sex had been determined prenatally had older brothers. The five girls whose sex had been determined prenatally either had a male twin or were incorrectly identified as male. Prenatal sex determination had been done for 21% (26/122) of boys admitted for inpatient care compared with 11% (19/173) seen as outpatients. Use of fetal sex determination increased with increasing monthly income (chi2 for trend = 6.384, P = 0.0115). None of the mothers who had had no education had used fetal sex determination, but among mothers with some education the frequency of use did not change with increasing education. The sex ratio of children born at the hospital rose from 107 boys/100 girls in 1982 to 132 boys/100 girls in 1993. CONCLUSIONS: Fetal sex determination was common, especially if the family already had daughters. Sex determination seems to be driven by a desire to have sons, with socioeconomic status and education having little effect. The lower prevalence of fetal sex determinations for girls is likely to be due to abortion of fetuses found to be female. PMID- 7888846 TI - Stress, anxiety, and depression in hospital consultants, general practitioners, and senior health service managers. AB - OBJECTIVE: To study stress, anxiety, and depression in a group of senior health service staff. DESIGN: Postal survey. SUBJECTS: 81 hospital consultants, 322 general practitioners, and 121 senior hospital managers (total 524). MAIN OUTCOME MEASURES: Scores on the general health questionnaire and the hospital anxiety and depression scale. RESULTS: Sixty five (80%) consultants, 257 (80%) general practitioners, and 67 (56%) managers replied. Of all 389 subjects, 183 (47%) scored positively on the general health questionnaire, indicating high levels of stress. From scores on the hospital anxiety and depression scale only 178 (46%) would be regarded as free from anxiety, with 100 (25%) scoring as borderline cases and 111 (29%) likely to be experiencing clinically measurable symptoms. The findings for depression were also of some concern, especially for general practitioners, with 69 (27%) scoring as borderline or likely to be depressed. General practitioners were more likely to be depressed than managers (69 (27%) v 4 (6%) scored > or = 8 on hospital anxiety and depression scale-D; P = 0.004) with no significant difference between general practitioners and consultants. General practitioners were significantly more likely to show suicidal thinking than were consultants (36 (14%) v 3 (5%); P = 0.04) but not managers (9 (13%)). No significant difference could be found between the three groups on any other measure. CONCLUSIONS: The levels of stress, anxiety, and depression in senior doctors and managers in the NHS seem to be high and perhaps higher than expected. PMID- 7888847 TI - Predictive value of continuous ambulatory electrocardiographic monitoring in elderly people. AB - OBJECTIVE: To determine the predictive value of findings on continuous ambulatory electrocardiographic monitoring in elderly subjects. DESIGN: Retrospective cohort study. Ten year follow up of randomly selected elderly subjects who participated in ambulatory electrocardiography study in 1982. Mortality data derived from official registers. SETTING: Turku, Finland. SUBJECTS: 480 people aged 65 or older in 1982 who were living in the community, of whom 72% agreed to participate. MAIN OUTCOME MEASURES: Mortality from cardiac and non-cardiac causes during 10 year follow up. RESULTS: In the univariate analysis adjusted for age, risk of death from cardiac causes was increased among those with ventricular ectopy of more than 100 beats during the day (odds ratio 2.6; 99% confidence interval 1.4 to 6.1) or at night (3.3; 1.1 to 9.8) and in those with multifocal ventricular ectopic beats during the day (2.3; 1.0 to 5.0) or night (3.0; 1.3 to 7.1) compared with those with no ventricular ectopy. Sinoatrial pauses exceeding 1.5 seconds during the day (4.5; 1.8 to 11.1) were also associated with excess mortality from cardiac causes. None of the findings on ambulatory electrocardiography predicted death from non-cardiac causes. A further study of explanatory variables in the stepwise logistic regression analysis showed that sinoatrial pauses exceeding 1.5 seconds (4.0; 95% confidence interval 1.8 to 8.9) and night time multifocal ventricular ectopy (2.7; 1.2 to 5.9) predicted excess mortality from cardiac causes independently of age or clinically evident heart disease. CONCLUSION: Daytime sinoatrial pauses exceeding 1.5 seconds and night time multifocal ventricular ectopy in the ambulatory electrocardiogram predict increased mortality from cardiac causes independently of clinically evident cardiac diseases in unselected elderly subjects. PMID- 7888848 TI - Back pain and risk of fatal ischaemic heart disease: 13 year follow up of Finnish farmers. PMID- 7888849 TI - Audit of secondary prophylaxis after myocardial infarction. PMID- 7888850 TI - Association between non-insulin dependent diabetes mellitus and non-Hodgkin's lymphoma. PMID- 7888851 TI - So stroke units save lives: where do we go from here? PMID- 7888852 TI - Cardiac arrest and hypertrophic cardiomyopathy. Role of the implantable defibrillator. PMID- 7888853 TI - New or old antidepressants? New is better. PMID- 7888854 TI - New or old antidepressants? Benefits of new drugs are exaggerated. PMID- 7888855 TI - The greying of Europe. AB - About a quarter of the population of Europe is now of pensionable age. Facilities for caring for very old or disabled people differ throughout Europe in scope and means of funding, and the countries of the European Union are far from equity in the status of pensioners. Health expectations have increased in older people- most of the calculated gain in life expectancy is likely to be without disability. Most countries now have specialist geriatric medicine facilities, and international research programmes are under way. PMID- 7888856 TI - ABC of breast diseases. Breast cancer: treatment of elderly patients and uncommon conditions. PMID- 7888857 TI - Fallout from Chernobyl. Belarus increase was probably caused by Chernobyl. PMID- 7888858 TI - Fallout from Chernobyl. Thyroid cancer in children increased dramatically in Belarus. PMID- 7888859 TI - Fallout from Chernobyl. Chromosomal abnormalities increased in Latvia. PMID- 7888860 TI - Fallout from Chernobyl. Leukaemia in Greece did not rise. PMID- 7888861 TI - Fallout from Chernobyl. Not all health problems seen close to Chernobyl can be attributed to radiation. PMID- 7888863 TI - Surgical removal of third molars. National audit figures awaited. PMID- 7888862 TI - Fallout from Chernobyl. Studies may have had inadequate statistical power. PMID- 7888864 TI - Surgical removal of third molars. Most referred patients have symptoms. PMID- 7888865 TI - Early mortality after dental operations. What constitutes a dental operation? PMID- 7888866 TI - Surgical removal of third molars. Each case needs careful thought. PMID- 7888867 TI - Future of preventive dentistry. PMID- 7888868 TI - Children's consent to treatment. PMID- 7888869 TI - Coronary heart disease in women. Adjustment for age changes results. PMID- 7888870 TI - Chronic back pain. PMID- 7888871 TI - Deaths due to coronary heart disease during sport. PMID- 7888872 TI - Preventing suicide. PMID- 7888873 TI - Obtaining useful data from primary care. PMID- 7888874 TI - Culyer report. PMID- 7888875 TI - Genocide in Rwanda. PMID- 7888876 TI - Health care reform in the US. PMID- 7888877 TI - Reperfusion injury after acute myocardial infarction. PMID- 7888878 TI - Racial discrimination in medicine. PMID- 7888879 TI - Analgesic headache. PMID- 7888881 TI - Community oriented primary care. PMID- 7888880 TI - Better ways of assessing health needs in primary care. PMID- 7888882 TI - Smuggling of plutonium poses major health threat. PMID- 7888883 TI - Dutch contraceptive plan attracts criticism. PMID- 7888884 TI - Italy has Europe's highest caesarean section rate. PMID- 7888885 TI - Chile stops controversial sterilization. PMID- 7888886 TI - Relation between maternal haemoglobin concentration and birth weight in different ethnic groups. AB - OBJECTIVE: To assess the relation of the lowest haemoglobin concentration in pregnancy with birth weight and the rates of low birth weight and preterm delivery in different ethnic groups. DESIGN: Retrospective analysis of 153,602 pregnancies with ethnic group and birth weight recorded on a regional pregnancy database during 1988-91. The haemoglobin measurement used was the lowest recorded during pregnancy. SETTING: North West Thames region. SUBJECTS: 115,262 white women, 22,206 Indo-Pakistanis, 4570 Afro-Caribbeans, 2642 mediterraneans, 3905 black Africans, 2351 orientals, and 2666 others. MAIN OUTCOME MEASURES: Birth weight and rates of low birth weight (< 2500 g) and preterm delivery (< 37 completed weeks). RESULTS: Maximum mean birth weight in white women was achieved with a lowest haemoglobin concentration in pregnancy of 85-95 g/l; the lowest incidence of low birth weight and preterm labour occurred with a lowest haemoglobin of 95-105 g/l. A similar pattern occurred in all ethnic groups. CONCLUSIONS: The magnitude of the fall in haemoglobin concentration in pregnancy is related to birth weight; failure of the haemoglobin concentration to fall below 105 g/l indicates an increased risk of low birth weight and preterm delivery. This phenomenon is seen in all ethnic groups. Some ethnic groups have higher rates of low birth weight and preterm delivery than white women, and they also have higher rates of low haemoglobin concentrations. This increased rate of "anaemia," however, does not account for their higher rates of low birth weight, which occurs at all haemoglobin concentrations. PMID- 7888887 TI - Aid to diagnosis of melanoma in primary medical care. AB - OBJECTIVE: To evaluate an intervention designed to reduce the number of benign melanocytic lesions excised from the skin. DESIGN: A randomised controlled field trial based in the medical practices of two cities. Examination of histopathological reports of 5823 melanocytic skin lesions excised over the intervention period and in the preceding six months. INTERVENTION: Medical practitioners were offered an algorithm and use of an instant developing camera. SETTING AND SUBJECTS: Over 50 medical practitioners, mostly in general practice, in each of two cities in tropical Queensland, Australia. MAIN OUTCOME MEASURES: Percentages of benign (neither malignant nor potentially malignant) melanocytic lesions excised during the two year intervention period. RESULTS: There were no significant differences in the percentages of benign lesions reported in the intervention and control cities before the intervention started (93.6% and 94.0%, respectively), but there was a significant difference afterwards (88.8% and 93.8%, P < 0.001). There was no difference in the percentage of invasive melanomas excised per month in the intervention city (3.4%) compared with control city (3.4%). CONCLUSION: Clinical diagnostic accuracy may be enhanced by offering to clinicians managing suspicious melanocytic skin lesions a simple algorithm and a camera with which to record the appearance of lesions objectively. PMID- 7888888 TI - Medical school applicants from ethnic minority groups: identifying if and when they are disadvantaged. AB - OBJECTIVE: To assess whether people from ethnic minority groups are less likely to be accepted at British medical schools, and to explore the mechanisms of disadvantage. DESIGN: Prospective study of a national cohort of medical school applicants. SETTING: All 28 medical schools in the United Kingdom. SUBJECTS: 6901 subjects who had applied through the Universities' Central Council on Admissions in 1990 to study medicine. MAIN OUTCOME MEASURES: Offers and acceptance at medical school by ethnic group. RESULTS: Applicants from ethnic minority groups constituted 26.3% of those applying to medical school. They were less likely to be accepted, partly because they were less well qualified and applied later. Nevertheless, taking educational and some other predictors into account, applicants from ethnic minority groups were 1.46 times (95% confidence interval 1.19 to 1.74) less likely to be accepted. Having a European surname predicted acceptance better than ethnic origin itself, implying direct discrimination rather than disadvantage secondary to other possible differences between white and non-white applicants. Applicants from ethnic minority groups fared significantly less well in 12 of the 28 British medical schools. Analysis of the selection process suggests that medical schools make fewer offers to such applicants than to others with equivalent estimated A level grades. CONCLUSIONS: People from ethnic minority groups applying to medical school are disadvantaged, principally because ethnic origin is assessed from a candidate's surname; the disadvantage has diminished since 1986. For subjects applying before A level the mechanism is that less credit is given to referees' estimates of A level grades. Selection would be fairer if (a) application forms were anonymous; (b) forms did not include estimates of A level grades; and (c) selection took place after A level results are known. PMID- 7888889 TI - Acceptance into medical school and racial discrimination. PMID- 7888890 TI - Incidence of melanoma in four English counties, 1989-92. PMID- 7888891 TI - Skin cancer: how accurate are local data? PMID- 7888892 TI - Leucopenia associated with lamotrigine. PMID- 7888893 TI - Thrombolysis and low back pain. PMID- 7888894 TI - Urinary retention with misuse of "ecstasy". PMID- 7888895 TI - General practitioners' attitudes to patients with a self diagnosis of myalgic encephalomyelitis. PMID- 7888896 TI - Transferring the costs of expensive treatments from secondary to primary care. AB - General practitioners, especially fundholders, are becoming increasingly concerned about being asked to prescribe treatments for their patients that are outside their therapeutic experience. They are concerned about the clinical responsibility for such prescribing and the effects on their budgets. In some specialties transferring the costs of expensive treatments from secondary to primary care (cost shifting) has become partly institutionalised because of the separate sources of funding for drugs prescribed in the two sectors. With increased efforts to control the rising costs of the drugs budget and the emergence of new expensive treatments, cost shifting will be a challenge to clinicians and purchasers as they strive for rational, cost effective prescribing. A review of the funding mechanisms for drugs prescribing and of the relation between the licensing process and the decision to support the use of a treatment in primary or secondary care is needed. PMID- 7888897 TI - Content of advertisements for junior doctors: is there sufficient detail? AB - OBJECTIVE: To determine whether employers follow BMA guidelines on advertisements when advertising for junior doctors. DESIGN: Survey of advertisements for junior doctors in the BMJ's classified advertisements supplement from 12 March to 14 May 1994. SUBJECTS: 300 advertisements for substantive posts for junior doctors. OUTCOME MEASURES: Compliance with BMA guidelines, compared by grade, specialty, and employer (trust or regional health authority); observation of any useful information not included in the guidelines. RESULTS: Only eight advertisements included all the recommended information. Amount of information given was related to grade, specialty, or employer in only one respect: advertisements for basic trainees were more likely than those for higher specialist trainees to include information on pay and hours of work (P < 0.001). CONCLUSION: Advertisements for junior doctors in the BMJ do not comply with BMA guidelines and often contain little useful information for potential applicants. PMID- 7888898 TI - Analysing your organisation and environment and setting its strategy. PMID- 7888900 TI - ABC of rheumatology. Gout, hyperuricaemia, and crystal arthritis. PMID- 7888899 TI - Meningeal granulomas: sarcoidosis or tuberculosis? Differentiation can be difficult. PMID- 7888901 TI - The inhumanity of medicine. Medical education is brutalising. PMID- 7888902 TI - The inhumanity of medicine. Audit of doctors and patients' views may help. PMID- 7888903 TI - The inhumanity of medicine. Medical students are positive about the future. PMID- 7888904 TI - Medical care continues to be important for health. PMID- 7888905 TI - Diagnosis and management of chronic sinusitis. Do not rely on computed tomography. PMID- 7888907 TI - Vitamin A supplementation in preschool children with acute diarrhoea. PMID- 7888906 TI - Carrier testing in children for cystic fibrosis. PMID- 7888908 TI - Management of childhood nephrotic syndrome. PMID- 7888909 TI - Eradication of Helicobacter pylori in management of peptic ulceration. Evidence supports eradication only in patients who have helicobacter and peptic ulceration. PMID- 7888910 TI - Management of stroke patients. PMID- 7888911 TI - BMA's representation of clinical and medical directors. Medical directors in Wales not represented. PMID- 7888912 TI - Getting started as a medical manager. PMID- 7888913 TI - Aircraft cabin pressure and parkinsonian symptoms. PMID- 7888914 TI - Health promotion in general practice. Focus on modification of risk factors and patients' perception of lifestyle. PMID- 7888915 TI - Travel prophylaxis. PMID- 7888916 TI - Out of hours visits. PMID- 7888917 TI - Stress in NHS consultants. PMID- 7888918 TI - The WHO: change or die. PMID- 7888919 TI - Copenhagen's challenge. PMID- 7888920 TI - Patterns of disease: diabetes mellitus and the rest. PMID- 7888921 TI - Violence versus reproductive health care. PMID- 7888922 TI - Gaps in law plugged for "mentally incapacitated". PMID- 7888923 TI - BMA criticises guidance on long term care. PMID- 7888924 TI - Husband wins compensation after laparoscopy death. PMID- 7888925 TI - Danish court clears drug firm of blood contamination. PMID- 7888926 TI - Australia continues debate on euthanasia. PMID- 7888927 TI - Making the most of aging populations. PMID- 7888928 TI - Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men. AB - OBJECTIVE: To examine the association between smoking, alcohol consumption, and the incidence of non-insulin dependent diabetes mellitus in men of middle years and older. DESIGN: Cohort questionnaire study of men followed up for six years from 1986. SETTING: The health professionals' follow up study being conducted across the United States. SUBJECTS: 41,810 male health professionals aged 40-75 years and free of diabetes, cardiovascular disease, and cancer in 1986 and followed up for six years. MAIN OUTCOME MEASURE: Incidence of non-insulin dependent diabetes mellitus diagnosed in the six years. RESULTS: During 230,769 person years of follow up 509 men were newly diagnosed with diabetes. After controlling for known risk factors men who smoked 25 or more cigarettes daily had a relative risk of diabetes of 1.94 (95% confidence interval 1.25 to 3.03) compared with non-smokers. Men who consumed higher amounts of alcohol had a reduced risk of diabetes (P for trend < 0.001). Compared with abstainers men who drank 30.0-49.9 g of alcohol daily had a relative risk of diabetes of 0.61 (95% confidence interval 0.44 to 0.91). CONCLUSIONS: Cigarette smoking may be an independent, modifiable risk factor for non-insulin dependent diabetes mellitus. Moderate alcohol consumption among healthy people may be associated with increased insulin sensitivity and a reduced risk of diabetes. PMID- 7888929 TI - Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men. AB - OBJECTIVE: To determine the risk factors for noninsulin dependent diabetes in a cohort representative of middle aged British men. DESIGN: Prospective study. SUBJECTS AND SETTINGS: 7735 men aged 40-59, drawn from one group practice in each of 24 towns in Britain. Known and probable cases of diabetes at screening (n = 158) were excluded. MAIN OUTCOME MEASURES: Non-insulin dependent diabetes (doctor diagnosed) over a mean follow up period of 12.8 years. RESULTS: There were 194 new cases of non-insulin dependent diabetes. Body mass index was the dominant risk factor for diabetes, with an age adjusted relative risk (upper fifth to lower fifth) of 11.6; 95% confidence interval 5.4 to 16.8. Men engaged in moderate levels of physical activity had a substantially reduced risk of diabetes, relative to the physically inactive men, after adjustment for age and body mass index (0.4; 0.2 to 0.7), an association which persisted in full multivariate analysis. A nonlinear relation between alcohol intake and diabetes was observed, with the lowest risk among moderate drinkers (16-42 units/week) relative to the baseline group of occasional drinkers (0.6; 0.4 to 1.0). Additional significant predictors of diabetes in multivariate analysis included serum triglyceride concentration, high density lipoprotein cholesterol concentration (inverse association), heart rate, uric acid concentration, and prevalent coronary heart disease. CONCLUSION: These findings emphasise the interrelations between risk factors for non-insulin dependent diabetes and coronary heart disease and the potential value of an integrated approach to the prevention of these conditions based on the prevention of obesity and the promotion of physical activity. PMID- 7888930 TI - Sleep related vehicle accidents. AB - OBJECTIVES: To assess the incidence, time of day, and driver morbidity associated with vehicle accidents where the most likely cause was the driver falling asleep at the wheel. DESIGN: Two surveys were undertaken, in southwest England and the midlands, by using police databases or on the spot interviews. SUBJECTS: Drivers involved in 679 sleep related vehicle accidents. RESULTS: Of all vehicle accidents to which the police were summoned, sleep related vehicle accidents comprised 16% on major roads in southwest England, and over 20% on midland motorways. During the 24 hour period there were three major peaks: at around 0200, 0600, and 1600. About half these drivers were men under 30 years; few such accidents involved women. CONCLUSIONS: Sleep related vehicle accidents are largely dependent on the time of day and account for a considerable proportion of vehicle accidents, especially those on motorways and other monotonous roads. As there are no norms for the United Kingdom on road use by age and sex for time of day with which to compare these data, we cannot determine what the hourly exposure v risk factors are for these subgroups. The findings are in close agreement with those from other countries. PMID- 7888931 TI - Sarcoidosis presenting after resection of an adrenocortical adenoma. PMID- 7888932 TI - Self reported hypertension among unemployed people in the United States. PMID- 7888933 TI - Randomised trial of lipid lowering dietary advice in general practice: the effects on serum lipids, lipoproteins, and antioxidants. AB - OBJECTIVE: To determine the relative efficacy in general practice of dietary advice given by a dietitian, a practice nurse, or a diet leaflet alone in reducing total and low density lipoprotein cholesterol concentration. DESIGN: Randomised six month parallel trial. SETTING: A general practice in Oxfordshire. SUBJECTS: 2004 subjects aged 35-64 years were screened for hypercholesterolaemia; 163 men and 146 women with a repeat total cholesterol concentration of 6.0-8.5 mmol/l entered the trial. INTERVENTIONS: Individual advice provided by a dietitian using a diet history, a practice nurse using a structured food frequency questionnaire, or a detailed diet leaflet sent by post. All three groups were advised to limit the energy provided by fat to 30% or less and to increase carbohydrate and dietary fibre. MAIN OUTCOME MEASURES: Concentrations of total cholesterol and low density and high density lipoprotein cholesterol after six months; antioxidant concentration and body mass index. RESULTS: No significant differences were found at the end of the trial between groups in mean concentrations of lipids, lipoproteins, and antioxidants or body mass index. After data were pooled from the three groups, the mean total cholesterol concentration fell by 1.9% (0.13 mmol/l, 95% confidence interval 0.06 to 0.22, P < 0.001) to 7.00 mmol/l, and low density lipoprotein cholesterol also fell. The total carotenoid concentration increased by 53 nmol/l (95% confidence interval 3.0 to 103, P = 0.039). CONCLUSIONS: Dietary advice is equally effective when given by a dietitian, a practice nurse, or a diet leaflet alone but results in only a small reduction in total and low density lipoprotein cholesterol. To obtain a better response more intensive intervention than is normally available in primary care is probably necessary. PMID- 7888934 TI - Influence of age on general practitioners' definition and treatment of hypertension. PMID- 7888935 TI - Drug treatment of Parkinson's disease. AB - A wide variety of drugs is available for treating Parkinson's disease, including anticholinergics, amantadine levodopa, dopamine agonists, and selegiline. In younger patients (less than 50) levodopa is usually delayed provided that adequate relief of symptoms can be achieved with other drugs. In older patients (greater than 70) levodopa should be started as soon as symptom relief is required. Between these ages there is no consensus, but at present most such patients should probably be given controlled release levodopa before a dopamine agonist is added. Fluctuations can often be alleviated by giving controlled release preparations of levodopa, by giving small doses at frequent intervals, by adding selegiline or a long acting oral agonist, or by subcutaneous apomorphine. Dyskinesia can be peak dose, diphasic, or "off period." The diphasic form is hardest to alleviate. Psychiatric side effects should initially be managed by changing the antiparkinsonian treatment before resorting to antipsychotic drugs. PMID- 7888936 TI - Cystic fibrosis presenting as hyponatraemic heat exhaustion. PMID- 7888937 TI - Consultants' workload in outpatient clinics. AB - The impact on hospital resources of variability in referral rates among general practitioners was of concern throughout the 1980s. The overall number of patients referred to outpatient clinics, however, has increased only slowly since the NHS began; in contrast, the number of new outpatients seen by each hospital consultant has declined appreciably. Ironically, despite this decline, further increasing the number of consultants in now being presented as a solution to the demand for outreach clinics in general practice. PMID- 7888938 TI - The World Health Organisation. Interview with the director general. Interview by Fiona Godlee. AB - Dr Hiroshi Nakajima was elected director general of WHO in 1988. Born in Japan, he trained as a psychiatrist before joining WHO in 1973. He was WHO's regional director for the Western Pacific from 1979 to 1988. His term of office has been marked by criticism of his management style and allegations of misuse of WHO's funds. I spoke to him at WHO's headquarters in Geneva in July. I have presented the interview in the form of questions and answers. It would be misleading, however, not to make clear that in doing so I have transcribed conversation which was at times extremely difficult to follow. I feel that it is important to emphasise this in the context of an interview with an international leader, one of whose primary tasks must be to communicate his views on health to people across the world. The interviews gave me first hand experience of the difficulties in communication that staff, diplomats, and others, including Japanese leaders, have consistently commented on since Dr Nakajima took office. PMID- 7888939 TI - ABC of rheumatology. Rheumatoid arthritis--I: Clinical features and diagnosis. PMID- 7888940 TI - Managing change. PMID- 7888941 TI - Mandatory drug tests in prisons. PMID- 7888942 TI - The WHO. Non-government organisations should be catalysts for change. PMID- 7888943 TI - The WHO. Education at prestigious centres is valuable. PMID- 7888944 TI - The WHO. New cases of leprosy are falling. PMID- 7888945 TI - The WHO. The tropical disease research programme has a coherent plan. PMID- 7888946 TI - The WHO. The WHO was in favour of social security. PMID- 7888947 TI - August: the killing season. Last week in July is a poor comparison. PMID- 7888948 TI - August: the killing season. Other measures of quality are needed. PMID- 7888949 TI - The WHO. Nursing is underrepresented. PMID- 7888951 TI - Nestle abides fully to WHO code on baby milk. PMID- 7888950 TI - Effects of health publicity on prevalence of smoking. PMID- 7888952 TI - Nocardia pericarditis. PMID- 7888953 TI - Interpreting hospital death rates. Can be difficult. PMID- 7888954 TI - Asthma trends. PMID- 7888955 TI - Care of dying patients in hospital. PMID- 7888956 TI - Smoking and death. PMID- 7888957 TI - Breast disease. PMID- 7888958 TI - Medical informatics. PMID- 7888959 TI - Preventing suicide. PMID- 7888960 TI - Generic inhalers for asthma. Money saved could be spent on patient education. PMID- 7888961 TI - Generic inhalers for asthma. Patients titrate dose against response. PMID- 7888962 TI - Report on Australian surgeons. PMID- 7888963 TI - Primary care and general practice. PMID- 7888964 TI - Allergy to colophony. PMID- 7888965 TI - Electronic health records. PMID- 7888966 TI - Leeches. PMID- 7888967 TI - Problems of overseas adoption. PMID- 7888968 TI - Early treatment of women with alcohol addiction (EWA): a comprehensive evaluation and outcome study. I. Patterns of psychiatric comorbidity at intake. AB - This paper deals with psychiatric comorbidity among 60 women problem drinkers treated in a specialized women-only treatment programme (EWA) at Karolinska Hospital, Stockholm, Sweden. The programme attracts women who have not been previously treated for alcohol problems. The methods used were structured interviews (SCID-I and SCID-II) applied at least 10 days after the start of treatment. All but two of the women had a definite alcohol dependence according to the DSM-III-R, and a majority (60%) also fulfilled the criteria for at least one psychiatric disorder during their lifetime. However, only 23% had a personality disorder (PD), and all subjects with a PD also had at least one Axis I disorder. The most common disorders were mood disorders (48%) and anxiety disorders (38%). However, alcohol dependence developed without definite pre existing psychiatric disorders among a substantial proportion of the women (40%). It remains to be seen whether and how psychiatric disturbances among female problem drinkers affect treatment compliance and long-term outcome. PMID- 7888969 TI - Inconsistencies in lifetime cocaine and marijuana use reports: impact on prevalence and incidence. AB - We evaluated inconsistencies in responses to questions about lifetime cocaine and marijuana use asked of nearly 10,000 respondents from the United States in the National Longitudinal Survey of Youth in 1984 and 1988. Our analyses showed that 14% of all responses on cocaine use and 17% of all responses on marijuana use were inconsistent in some way. The types of inconsistencies varied according to the substance; cocaine reports yielded more inconsistencies with regard to timing of first use, while for marijuana most of the inconsistencies were with respect to use disclosure. For both substances, lower level users were more likely to be inconsistent in their reports of drug use. Alternative methods for handling inconsistencies affected estimates of incidence and prevalence. Inconsistencies also varied according to respondent race/ethnicity. Implications of these findings for program evaluation are discussed. PMID- 7888970 TI - Controlled evaluation of a general practice-based brief intervention for excessive drinking. AB - In a controlled evaluation of general practitioner (GP)-based brief intervention, 378 excessive drinkers identified opportunistically by screening in 40 group practices in metropolitan Sydney were assigned to groups receiving: (i) a five session intervention by the GP (the Alcoholscreen Program); (ii) a single session of 5 minutes' advice by the GP plus a self-help manual (minimal intervention); (iii) an alcohol-related assessment but no intervention; (iv) neither intervention nor assessment. Among all patients allocated to receive it, the Alcoholscreen Program did not result in a significantly greater reduction in consumption at follow-up than control conditions but patients offered Alcoholscreen reported a significantly greater reduction in alcohol-related problems in the period to 6 months follow-up. A greater proportion of patients who returned for the second Alcoholscreen visit were drinking below recommended levels at follow-up than in the remainder of the sample. There was no evidence that minimal intervention or alcohol-related assessment were effective in reducing alcohol consumption or problems. Implications for further research into GP-based brief interventions are discussed. PMID- 7888971 TI - The language of industry: toward a definition of liquorspeak. PMID- 7888972 TI - The drugs in pregnancy service. PMID- 7888973 TI - HIV transmission in prison. PMID- 7888974 TI - User groups. PMID- 7888975 TI - Do alcohol pharmacokinetics in women vary due to the menstrual cycle? AB - Many authors in the alcohol field believe that the physiological responsiveness of women to alcohol varies during the menstrual cycle, due to changes in levels of sex steroid hormones. Statements about this issue are very contradictory, however. The aim of this review was to decide what valid evidence was available on this issue. Three criteria were set to assess the validity of the reviewed studies: (1) was a within-subjects design used with normally cycling subjects, (2) were the time points selected for testing characterized by significant variations in sex steroid activity, and (3) was it verified whether ovulation occurred in the subjects by measuring levels of sex steroids? Two of the 11 studies we examined met these criteria. These studies, emanating from the same laboratory, found that alcohol elimination increased, by about 14%, during the luteal phase compared to other phases of the cycle. The results were discussed in relation to other research regarding effects of sex steroids on alcohol metabolism. It is concluded that there is no evidence that menstrual cycle causes significant instability in alcohol pharmacokinetics in women. PMID- 7888976 TI - Playing fair: science, ethics and scientific journals. PMID- 7888977 TI - Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice. AB - The transdermal nicotine patch has proved an effective aid to smoking cessation. The ease of securing good compliance gives it a potential advantage over nicotine gum as an adjunct to brief advice and support in primary care settings where the major public health impact is obtained. In a preliminary report of half the sample of a randomized placebo controlled trial, we showed the patch to be effective in a general practice setting. We report here the definitive results of the full sample, including dose effects, predictors of outcome and other issues of theoretical and practical interest. A total of 1200 heavy smokers (> or = 15 per day), attending 30 general practices in 15 English counties received brief GP advice, a booklet and 16 hours per day patch treatment for 18 weeks. Dose increase and abrupt vs. gradual reduction of patch dosage were also randomized and follow-ups conducted at 1, 3, 6, 12, 26 and 52 weeks. Outcome was measured by self-reported complete abstinence from week 3 to 52 with biochemical validation at all follow-up points. Nicotine patch treatment doubled the rate of continuous abstinence up to 1 year (nicotine 9.6%, placebo 4.8%, p < 0.01); it most likely worked by reducing withdrawal symptoms. It enhanced cessation during the first week and reduced relapse during the second week. The dose increase after week 1 produced no sustained increase in cessation. Gradual reduction was no better at preventing relapse than abrupt withdrawal of patches after week 12. Whether relapse would have increased by ending treatment at some point between weeks 3 and 12 was not tested. Although pre-treatment dependence on cigarettes was prognostic of failure, the patches were equally helpful to both highly and less dependent smokers. Patches were particularly helpful to smokers with pre treatment subclinical dysthymic symptoms. All but one of the 96 subjects eventually achieving long-term abstinence in the study quit during the first week of cessation. PMID- 7888979 TI - A profile of Chinese alcoholics in Singapore. AB - Eighty-five Chinese alcoholics, referred consecutively to the psychiatric unit of a general hospital, were assessed with the Alcohol Problems Questionnaire (APQ) and the Severity of Alcohol Dependence Questionnaire (SADQ). There were 72 men (mean age 44.3, SD 13.9) and 13 women (mean age 36.7, SD 11.6). The common alcohol-related problems reported concerned physical health, finance, work, friends, depression and marriage. The SADQ score for men was 19.6 (SD 7.8) and women 15.6 (SD 8.4). Highly significant Pearson product moment correlations were found between the SADQ score and APQ subscales in physical health, depression and finance; but there was no correlation with children or legal (police) problems. The strongly positive correlation between the SADQ and APQ scores were independent of the quantity of alcohol consumption. Female drinkers had more depressive symptoms than males, but there was no significant difference in alcohol-related problems pertaining to physical health, work, marriage, finance or friends for male or female drinkers. PMID- 7888978 TI - Risk factors for inhalant abuse in juvenile offenders: the case of Mexico. AB - During the last two decades the abuse of inhalants and other addictive substances has received considerable attention in Mexico. Although substance abuse seems to affect everyone, adolescents seem to be at higher risk, and although researchers have identified the links between substance abuse and delinquency, there is not enough scientific information to explain the reason. A cross-sectional study was designed to examine the relationship between known risk factors and inhalant abuse among a group of Mexican juvenile offenders. Of the 626 subjects studied, 58% reported use of different drugs, and of them 23% abused inhalants. Gender, low socio-economic level and labor status were the principal risk factors associated with inhalant abuse. According to attributable risks calculated, and taking into account the methodological limitations of the study, the authors suggest some preventive actions to decrease inhalant abuse in the population studied. PMID- 7888980 TI - Regional differences in drinking among Finnish adolescents. AB - Regional variation in health behaviour can be explained either by differences in the socio-demographic characteristics of population or can be based on some other differences, such as cultural traditions. The purpose of this study was to find out the extent to which provincial differences in adolescents' alcohol use can be reduced to socio-demographic differences between adolescent populations of the provinces. A cross-sectional postal survey data from the Adolescent Health and Lifestyle Survey was used. In 1991, the sample was weighted according to the size of the province. It represented 16- and 18-year-old Finns in each province (n = 6600). Provincial variation in weekly alcohol use was reduced for about one quarter and the ordering of the provinces in drinking changed when the differences in urbanization level between provinces were adjusted. When socio demographic factors were adjusted two provinces still differed significantly from the other provinces. Our study shows that variation in alcohol use among Finnish adolescents is related to where they live, and not simply to demographics. PMID- 7888981 TI - Drug and alcohol use and family characteristics: a study among Brazilian high school students. AB - The present work employs a multivariate analysis technique to study, simultaneously, family relations and alcohol/drug consumption among 16,378 Brazilian high-school students. The analysis is centered on the relation between subjective or objective family situations and consumption. Subjective situations are measured by adolescents' perception of their families, that is, the family's environmental "climate"--whether violent situations occur at home, whether there is frequent dialogue about the youngsters' problems, and whether they perceive interest on the part of parents. Objective situations refer to the conjugal status of parents. Results pointed to family violence as the factor most frequently associated with alcohol/drug use behavior. It was also found that the family's environmental climate constitutes a more important factor than the conjugal status of parents, when it comes to the development of drug use behavior. Therefore, the impact of this last variable (whether parents are living together) is determined by environmental conditions: when those conditions are favorable (no violence, problems habitually talked about, parents concerned with their offspring) the fact that parents were effectively living together meant a smaller probability of alcohol/drug use; when these conditions were unfavorable, the same fact was associated with a greater probability of consumption. PMID- 7888982 TI - Patterns of alcohol consumption and related problems in the general population of Greece. AB - This paper focuses on patterns of alcohol consumption and related problems, based on a nation-wide home survey sample of 4290 respondents aged 12-64 years. The prevalence of lifetime, past year and past month alcohol use, as well as levels of quantity of alcohol consumed and the reported alcohol-related problems, are presented. Frequency and quantity of consumption increases as age increases. Males were found to drink alcohol more frequently and in higher quantities than females. A higher proportion of young adults reported alcohol-related problems, in comparison to the other age groups. Regional variations in the frequency of consumption of alcohol were observed. However, no differences were found in the geographic distribution of persons of all age groups reporting alcohol-related problems. Respondents of all groups with two or more alcohol related problems expressed a high number of dysphoric and depressive symptoms. Finally, a stepwise discriminant analysis revealed certain socio-demographic, familial, psychological and medical factors to discriminate optimally the "problem" and "non-problem" drinkers in both adolescent and adult age groups. PMID- 7888983 TI - Effects of citalopram and a brief psycho-social intervention on alcohol intake, dependence and problems. AB - Citalopram (C) decreased alcohol intake and desire to drink in short-term (2-4 weeks) studies with no other treatment. We tested the long-term effects of C combined with a brief psycho-social intervention. After a 2-week baseline, mildly/moderately dependent alcoholics (35 males, 27 females) were randomized, double-blind to 12 weeks of C 40 mg/day (n = 31) or placebo (P) (n = 31) and a brief psycho-social intervention with follow-ups at 4 and 8 weeks post-treatment. Alcohol intake was monitored daily and alcohol dependence (ADS) and problems (MAST) were assessed at intake and post-treatment. During the first week, the decrease (%) from baseline daily alcoholic drinks (mean +/- SEM) was greater with C (47.9 +/- 5.1 from 6.5 +/- 0.6) than with P (26.1 +/- 4.2 from 5.8 +/- 0.4) (p < 0.01). However, the 12-week decreases with C (35.1%) and P (38.8%) were similar. There were gender differences within the C group. The males had higher MAST scores at intake (mean +/0 SEM = 10.4 +/- 0.8; n = 15) than the females (6.4 +/- 0.9, n = 16) (p < 0.01) and were slightly heavier drinkers during baseline (7.1 +/- 0.9 vs. 5.9 +/- 0.9 drinks/day, NS). The response to C was greater in males (44% decrease) than females (26%) (p < 0.05) and correlated with MAST scores (r = 0.44, p = 0.01), but not with baseline alcohol intake (r = 0.2, NS). Craving and liking for alcohol and alcohol dependence (ADS) and problems (MAST) decreased similarly with C and P (p < 0.01). Thus, the short-term effects of C were replicated but no long-term effect was detected. Tolerance to citalopram, perhaps through some adaptive neurobiological changes, may have developed. The potential therapeutic use of C as a useful pharmacological adjunct in alcoholics remains to be determined. PMID- 7888984 TI - Hypertension and blood pressure awareness among American Indians of the northern plains. AB - This study compared self-reported and measured blood pressure among American Indians of the northern plains. In 1986, a group of American Indians from the northern plains was administered the Centers for Disease Control Behavioral Risk Factor Survey (which included a question about previous blood pressure measurements) and a health risk appraisal (which included blood pressure measurement). Approximately 18% of the respondents reported being told by a doctor, nurse, or other health professional that they had high blood pressure, and 11% actually had measured blood pressures of at least 140/90 mm Hg. Overall, only 50% of hypertensive participants correctly identified themselves as hypertensive (sensitivity); specificity was 92%, predictive value positive was 43%, predictive value negative was 94%, and efficiency (the proportion of individuals who correctly classified their blood pressure status as high or normal) was 87%. These findings agree with similar studies of hypertension awareness, and they indicate that lack of this awareness remains a significant problem in the fight against cardiovascular diseases and premature death among American Indians. PMID- 7888985 TI - Plasma fibrinogen and other cardiovascular risk factors in urban American Indian smokers. AB - Although cardiovascular disease is an important health concern for urban American Indians, little information is available on their risk factor levels. We examined several risk factors (plasma fibrinogen, body size and shape, and serum cholesterol) among American Indian smokers in a smoking cessation trial at four urban Indian health clinics. The American Indian smokers had higher levels of fibrinogen and abdominal obesity than African-American and white smokers in two other population-based studies. Serum cholesterol concentrations among the American Indian smokers were lower than typical values among US whites. Among the American Indians, plasma fibrinogen was higher in women (mean: 338 mg/dL) than in men (mean: 318 mg/dL); positively correlated (P < .05) with age, body mass index, and waist-hip ratio; and negatively correlated with serum cholesterol level. Even though average cholesterol levels were not high, the combination of abdominal obesity and high fibrinogen among American Indians, particularly smokers, may increase their risk of cardiovascular disease. PMID- 7888986 TI - Body mass index as a predictor of systolic blood pressure in a multiracial sample of US schoolchildren. AB - We examine the relationship between body mass index (weight divided by height squared) and systolic blood pressure and the implications of using obesity as a criterion for blood pressure screening in a multiracial sample of 11,370 schoolchildren. For the entire sample, the zero-order correlation between body mass index and systolic blood pressure was 0.39. Correlations were strongest among Hispanics (r = .51) and weakest among blacks (r = .29). Among white, black, Asian, and Hispanic boys with body mass index values in the upper decile, the odds of having elevated systolic blood pressure (above the 95th percentile) were significantly higher than among individuals in the bottom decile. Among girls with body mass index values in the top decile, higher odds of hypertension were observed only for whites and Hispanics. For the entire population, the sensitivity of screening only children with body mass index values in the top quartile was 52%. The sensitivity of this cutpoint was higher for Hispanics, although 36% of those with elevated systolic blood pressure would still be missed. These data confirm that overweight children are significantly more likely to have elevated systolic blood pressure and total blood cholesterol levels and that weight reduction may play an important role in the primary prevention of coronary heart disease among children of various ethnic backgrounds. Selective screening of overweight children, however, does not appear warranted. PMID- 7888987 TI - Correlates of blood pressure in Yanomami Indians of northwestern Brazil. AB - We determined associations of measures of body habitus with blood pressure for 100 adult Yanomami Indians (61 men, 39 women) examined during February and March 1990. Measurements included body weight and height, four skinfolds (triceps, subscapular, suprailiac, abdomen), four circumferences (wrist, upper arm, abdomen, hip), systolic and diastolic blood pressures, pulse rate, and estimated age. Various indices of fat distribution were determined from the measurements of skinfolds, circumferences, weight, and height. Estimated age averaged 35.0 years in men and 33.4 years in women (range: 15 to 63 years). Mean systolic and diastolic blood pressures were low in both men (104.8/70.4 mm Hg) and women (94.8/63.5 mm Hg), as was body mass index (men: 20.7; women: 21.4 kg/m2). In Yanomami women, all four skinfolds, wrist circumference, and the indices of hip and abdominal fat were significant correlates of systolic blood pressure, while the abdominal skinfold and wrist and hip circumferences correlated significantly with diastolic blood pressure. Among men, there was a negative correlation between estimated age and systolic blood pressure and a positive correlation between BMI and upper arm and hip circumferences and systolic blood pressure. There was a significant positive correlation between wrist, upper arm, and hip circumferences and diastolic blood pressure among Yanomami men. We used stepwise regression to generate sex-specific predictive equations for blood pressure. For men, estimated age and hip circumference, and for women, abdominal skinfold measurement and age were included in the model for systolic blood pressure. Among men, wrist circumference and height, and among women, wrist circumference alone entered the model for diastolic blood pressure. On the basis of these results, we suggest that even in a low-blood pressure, low-body fat, no-salt setting, systolic blood pressure is associated with the amount and placement of adipose tissue. However, diastolic blood pressure is more closely correlated with skeletal size. PMID- 7888988 TI - Is race a risk factor or a risk marker for preterm delivery? AB - Reasons for the persistent difference in rates of preterm delivery among black and white women are not clear. Known risk factors explain very little of the variance. Recent studies have shown that social class does not fully account for poor pregnancy outcomes among black women. Cultural and environmental factors that vary between the races, but not between the different socioeconomic levels within a race, may account for some of the unexplained ethnic differences in preterm delivery. Any potentially negative exposure that is distributed differentially between racial groups warrants particular attention. The major hypothesis of this research is that US black women are chronically exposed to specific stressors that adversely affect the outcomes of their pregnancies. A psychosocial stress model has been proposed to explain the complex interactions of social, environmental, and medical factors that are unique among women of color. To generate data for the stress model, a research strategy has been designed to identify psychosocial and behavioral risk factors that have a physiologic impact on pregnancy outcome. We propose that race is a marker for this stress but is not in itself a risk factor for preterm delivery. PMID- 7888989 TI - Skin color, ancestry, and blood pressure among whites in Erie County, New York. AB - This study examines (1) the construct validity of a rank-order skin color measure and (2) interrelationships of skin color, ancestry, and blood pressure in a random survey of 763 white non-Hispanic and white Hispanic household residents in Erie County, NY. Skin color was significantly lighter among older respondents (P < .001) and among females (P < .0001). Skin color was lightest among Northern Europeans and darkest among Mediterraneans and white Hispanics (P < .0001). Higher systolic blood pressure was significantly associated with both darker skin color (P < .05) and northern European ancestry (P < .05). Several mechanisms to account for these findings are proposed. PMID- 7888990 TI - The social context of HIV transmission in the African-American community. AB - The concept of acquired immune deficiency syndrome (AIDS) as a behavioral problem, and the emphasis placed by researchers on race and ethnicity as "risk factors," have led to research focused on the "risk behaviors" of historically oppressed groups and a continuing social policy thrust that "blames the victim." Disproportionate numbers of AIDS cases have been reported among African Americans, and these cases are not evenly distributed throughout the nation. This geographical variation and distribution of AIDS among African Americans suggests that there are forces in society that impact African-American communities in differential ways. A review of alternate models presented in the scientific literature reveals that some attention is being given to reconceptualizing AIDS as a disease to be understood within the context of factors that affect the African-American community, rather than as a problem of personal behavior. The current status of "contextual approaches" found in the health and social science literature over a 5-year period (1987 to 1992) was assessed. Literature surveyed includes studies from the fields of social epidemiology, public health, and social science that address the issue of AIDS in the African-American community from a contextual perspective--that is, studies that seek to explain key issues within a framework that allows a "community-in-environment" analysis, as opposed to a behavioral perspective. Analysis of these contextual approaches indicates that dynamics external to individuals must be clarified to better understand the disparate pattern of AIDS among African Americans and whites. PMID- 7888991 TI - Oral contraceptive use and blood pressure levels among women workers in Sao Paulo, Brazil. AB - Oral contraceptive use has been increasing in Brazil since the late 1970s, and oral contraceptives have been associated with higher incidence of cardiovascular diseases, including hypertension, since their release in the United States and Europe. We examined the association between oral contraceptive use and blood pressure levels in 1457 workers from 10 sectors of the economy, between the ages of 15 and 49 years, in Sao Paulo, Brazil. Oral contraceptive use was associated with higher age, lower parity, higher income, white ethnic group, and administrative occupations. Using multiple linear regression and logistic regression techniques, we evaluated blood pressure and hypertension differences between users and nonusers. Oral contraceptive users had a mean systolic blood pressure 2.6 mm Hg higher than nonusers after adjustment for multiple potential confounders, including age, income, parity, ethnicity, body mass index, and occupation. There was a statistically significant positive trend between length of time on oral contraceptives and mean systolic blood pressure levels. After adjustment for demographic and social variables, there were no differences between whites and blacks. Oral contraceptive users have an adjusted odds ratio for hypertension of 2.66 (95% CI: 1.51-4.70). The finding of an increasingly positive association between oral contraceptive use and mean systolic blood pressure level suggests cause and effect. This observation has substantial importance because systolic blood pressure is considered the primary predictor of blood pressure-associated morbidity and mortality. This may pose a particular problem in Brazil, since most women on oral contraceptives are not under medical supervision. PMID- 7888992 TI - Hypertension, diabetes, and obesity in Barbados: findings from a recent population-based survey. AB - A stratified random sample of 464 persons aged 40 to 79 years, drawn from enumeration registers in the Bridgetown area of Barbados, participated in this survey. The prevalence of hypertension (defined as systolic blood pressure of at least 160 mm Hg, diastolic blood pressure of at least 95 mm Hg, or use of antihypertensive medication) was 47% and 43% for women and men, respectively. Diabetes was present in 17% of all subjects (18% of women and 15% of men). Of the 209 hypertensive subjects, 82% were aware of their blood pressure status. The proportion of previously diagnosed hypertensive subjects on medication was 72% for men and 68% for women. Fifty-three percent of men and 42% of women were overweight (body mass indices [weight in kilograms divided by height in meters squared] between 25 and 30). However, 30% of women and 10% of men were obese (body mass indices over 30), supporting the growing recognition of the marked gender disparity in obesity among persons of African origin in the Caribbean. Body mass index was positively associated with hypertension (OR = 1.33; 95% CI: 1.1-1.6). Obese persons experienced a 2.6 times greater risk of hypertension compared to those with body mass indices below 25. Similar statistically significant associations were observed between diabetes and body mass index: OR comparing body mass index over 30 with body mass index under 25 was 2.5 (95% CI: 1.3-5.1) for all subjects, 1.0 (0.3-4.1) for men only, and 5.2 (1.9-14) for women only. Preventing obesity in this population could reduce the incidence of hypertension and diabetes by approximately 30% and 33% among men and women, respectively. PMID- 7888993 TI - Available epidemiologic data on New York's Latino population: a critical review of the literature. AB - The increasing diversity of New York's Latino population creates complex challenges for the health care provider and planner, such as how to plan for divergent health risks, disease patterns, and health behaviors. However, most research on Latinos has been done in the southwestern United States. This paper reviews the epidemiologic data published since 1980 on Latino groups in New York State. The review covers the following areas: maternal and child health, infectious diseases, depression, tobacco and substance use, chronic diseases, neoplasms, and mortality statistics. We compare New York data with studies done in other areas of the United States. We identify serious methodological shortcomings in the epidemiological assessment of New York's Latino population, including (1) imprecise definition of "Latino," (2) misclassification, (3) census undercount of minority groups, and (4) lack of data on socioeconomic status. We argue that the epidemiological and cultural diversity of Latino groups demands the inclusion of such variables as place of birth, length of stay, and language preference in research and service statistics. This would facilitate targeted program planning and help to determine environmental, sociopolitical, behavioral, and genetic influences on diseases. PMID- 7888994 TI - [Features of inhibition of butyrylcholinesterase and carboxylesterase hydrolysis of fluoroanhydride esters by beta,beta-diphenylethylphosphonic acid]. PMID- 7888995 TI - [Structure-function organization of uridine phosphorylase from Escherichia coli]. PMID- 7888996 TI - [Cloning and expression of a protein coding the first translation frame of the jockey mobile genetic element in E. coli]. PMID- 7888997 TI - [The effect of mineral waters of differing chemical composition on the regenerative processes in tissue during the postradiation period]. PMID- 7888998 TI - [The effect of 1-chloromethylsilatrane on biomechanics of bone tissue during hypodynamia]. PMID- 7888999 TI - [Extracellular virus-like particles retrotransposon Gypsy (MDG 4) as an infectivity factor]. PMID- 7889000 TI - [Change in the chemotherapeutic sensitivity and cytogenetic characteristics during lengthy passage of tumors with the multidrug resistance phenotype and genotype]. PMID- 7889001 TI - Blood cell transplantation: report from an International Consensus Meeting. AB - An International Consensus Meeting on blood cell transplantation took place in Heemskerk, The Netherlands on 27-29 June 1994. The term 'blood cell transplantation' was preferred to peripheral blood stem cell transplantation. The following issues were addressed: stem cell assessment and ex vivo expansion, techniques for stem cell mobilization, applications of blood cell transplantation, malignant cell contamination and allogeneic blood cell transplantation. PMID- 7889002 TI - Cytokine gene expression by concanavalin A-stimulated peripheral mononuclear cells after bone marrow transplantation: an indicator of immunological abnormality due to chronic graft-versus-host disease. AB - The response of IFN-gamma, IL-2 and IL-5 mRNA expression to the stimulation of concanavalin A (Con A) in peripheral blood mononuclear cells (PBMC) after bone marrow transplantation (BMT) was analyzed using reverse-transcriptase polymerase chain reaction (RT-PCR) to assess the recovery of T cell function. The subjects were 23 patients undergoing allogeneic BMT, 1 syngeneic BMT, 1 autologous BMT and 2 normal individuals. IFN-gamma mRNA expression increased after Con A stimulation in 6 patients who had limited chronic graft versus host disease (GVHD), 14 patients who did not have chronic GVHD, each one patient receiving syngeneic and autologous BMT and 2 normal individuals. On the other hand, IFN-gamma mRNA expression was not increased by Con A stimulation in 4 patients who had extensive chronic GVHD. Also, the concentration of IFN-gamma in cultured medium in a patient with extensive chronic GVHD was not detectable. A similar low response of IL-2 and IL-5 mRNA expression to Con A was observed in these patients with extensive chronic GVHD. These findings indicate that the cytokine productive capacity of T cell (IFN-gamma and IL-2 could be produced by type 1 T helper (Th1) cells and IL-5 could be produced by type 2 T helper (Th2) cells) was suppressed in patients who had extensive chronic GVHD, while that capacity was almost normal in patients without chronic GVHD and with limited chronic GVHD. Therefore, the analysis of cytokine gene response to Con A stimulation may provide useful information regarding immune reconstitution after BMT. PMID- 7889003 TI - Viability of haemopoietic progenitors from whole blood, bone marrow and leukapheresis product: effects of storage media, temperature and time. AB - High-dose cytotoxic chemotherapy can be supported with autologous haemopoietic cells. Cryopreserved bone marrow has conventionally been used for this but blood stem cells are now in common use. We have examined different storage conditions for haemopoietic cells from bone marrow, leukapheresis product and whole blood primed with chemotherapy and filgrastim. The mean number of GM-CFC surviving cryopreservation was 80% in leukapheresis product (95% CI 66-96). At 4 degrees C, GM-CFC viability in all three sources of haemopoietic progenitors declined at the same rate, with mean recovery at 24 h of 90% (95% CI 82-98), at 48 h of 68% (95% CI 61-75) and at 72 h of 47% (95% CI 40-53). Progenitors remained viable for longer in autologous serum and citrate phosphate dextrose or Iscove's medium than in phosphate buffered saline. There was no significant difference in GM-CFC recovery from whole blood or whole blood buffy layer at 4 degrees C. The capacity to generate and sustain haemopoiesis in long-term culture is a feature of the more primitive progenitor cells. This capacity was similar in cryopreserved bone marrow and leukapheresis product, cryopreserved or stored for up to 5 days at 4 degrees C, suggesting that long-term culture-initiating cells are more resilient than colony-forming cells when cryopreserved or stored at 4 degrees C. These data indicate that primed whole blood, in addition to leukapheresis product and bone marrow, could be stored at 4 degrees C and used to support multicyclic high-dose chemotherapy. PMID- 7889004 TI - Induction of graft-versus-leukemia (GVL) activity in murine leukemia models after IL-2 pretreatment of syngeneic and allogeneic bone marrow grafts. AB - To investigate GVL effects, Balb/c mice (H-2d) received 5 x 10(5) A20 (B cell leukemia) or 1 x 10(6) WEHI-3 (myelomonocytic leukemia) cells. These cell lines lead to death after a median of 19 (WEHI-3) or 30 days (A20). A lethal dose of total body irradiation followed by syngeneic BMT resulted in significantly prolonged survival of leukemia-bearing animals. Transplantation of (C57 x Balb/c)F1 (H-2bxd) allogeneic, but GVH-non-reactive marrow grafts differentially influenced the relapse rates in the two leukemia models. Whereas allogeneic BMT reduced the relapse rates in A20-bearing mice, the leukemia-free survival was not improved in mice bearing the leukemia WEHI-3 compared with syngeneic BMT. Pre treatment of allogeneic (C57 x Balb/c)F1 or syngeneic Balb/c marrow cells with 200 U/ml IL-2 for 24 h did not reduce relapse rates in animals inoculated with A20 leukemia cells compared with unmanipulated bone marrow. In contrast, IL-2 treatment of syngeneic or allogeneic GVH non-reactive donor marrow significantly decreased the relapse rate in mice inoculated with WEHI-3 leukemia cells. The NK cell-mediated lysis of cultured leukemia cells was determined in vitro using a conventional 56Cr-release assay. Our data revealed a strong correlation between the level of natural killer activity determined in vitro and GVL activity in vivo. PMID- 7889006 TI - Transition of T cell receptor gamma/delta expressing double negative (CD4-/CD8-) lymphocytes after allogeneic bone marrow transplantation. AB - We studied peripheral blood CD4-CD8- gamma/delta T cells in recipients of allogeneic marrow grafts, using three-color immunofluorescence and flow cytometry, and investigated changes in their numbers in relation to the administration of hematopoietic growth factors or chronic graft-versus-host disease (GVHD). In the early post-bone marrow transplantation (BMT) period, the relative and absolute numbers of peripheral CD4-CD8- gamma/delta T cells in 22 allogeneic marrow graft recipients in relation to the use of hematopoietic growth factors were studied. During the first 4 weeks, increased numbers of CD4-CD8- gamma/delta T cells were observed in recipients of either recombinant human granulocyte colony-stimulating factor (rhG-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF). However, 4-8 weeks after BMT, the number of these cells was similar in both groups whether or not growth factors had been administered. At a later stage after BMT (3-12 months), peripheral CD4-CD8- gamma/delta T cells from 43 allogeneic BMT recipients were studied. These cells were markedly decreased in patients with chronic GVHD, and this decrease correlated closely with the clinical signs of chronic GVHD. These results suggest that CD4-CD8- gamma/delta T cells may play an important role in the recovery of neutrophils associated with growth factors during the very early post-BMT period, and in the immunodeficient state of chronic GVHD at a later stage after BMT. PMID- 7889005 TI - Endogenous superantigens in allogeneic bone marrow transplant recipients rapidly and selectively expand donor T cells which can produce IFN-gamma. AB - Despite the existence of many non-MHC disparities between MHC matched but non-MHC mismatched donors and recipients, graft-versus-host disease (GVHD) is not clinically apparent following a significant number of allogeneic bone marrow transplants (BMT) in experimental animals. The present studies examined V beta TcR expression and IFN-gamma production by donor T cells in a BMT model involving an MHC matched, allogeneic donor-recipient combination which included a unidirectional superantigen disparity (Mls). B10.D2-->BALB/c, but not BALB/c- >B10.D2 recipients develop GVHD and mortality ensues 8-12 weeks post-transplant. During the first 2 weeks post-transplant of B10.D2-->BALB/c, approximately 50% of all Thy1.2+ spleen and lymph node cells were found to express T cell receptors utilizing V beta 3. A similar rapid and selective expansion of V beta 3+ TcR bearing donor T cells was detected in two other H-2 matched superantigen disparate donor-recipient BMT combinations. An increased percentage of V beta 3+ T cells was noted among both the CD4+ and CD8+ populations. Thus, in these donor/recipient combinations, all TcR families were not equally expanded early following transplant. At 4-10 days post-transplant, IFN-gamma specific mRNA was readily detected in the spleens of B10.D2-->BALB/cBMT recipients containing large numbers of V beta 3+ T cells. Moreover, V beta 3+ donor T cells from these recipients contained IFN-gamma mRNA. Specific stimulation in vitro with immobilized anti-TcR moAbs demonstrated that V beta 3+ T cells secreted a large amount of the total IFN-gamma levels detected. The ability of endogenous superantigens to activate large numbers of T cells which can produce cytokines after BMT indicates that when present, such antigenic differences may contribute to events occurring during initial graft-versus-host reactions. Such antigens could therefore participate in the events influencing whether GVHD develops following BMT between certain donors and recipients. PMID- 7889007 TI - Parameters of the fibrinolytic system in patients undergoing BMT: elevation of PAI-1 in veno-occlusive disease. AB - Veno-occlusive disease (VOD) represents one of the more frequent and most severe complications after BMT. The pathophysiology of VOD is poorly understood. To investigate a possible link between endothelial cell damage and VOD, tissue plasminogen activator (tPA) and its inhibitor (PAI-1) were measured in 32 patients as endothelial cell-derived parameters of the fibrinolytic system. A nearly fivefold increase (mean 103.9 ng/ml, range 22.6-582.4 ng/ml, p < 0.05) in PAI-1 levels was found in the four patients who developed VOD compared with patients without this complication (mean 22.2 ng/ml, range 1.4-131.6 ng/ml). No significant difference was found in tPA levels between patient groups with or without VOD or other complications following BMT, indicating a shift of the fibrinolytic balance towards hypofibrinolysis particularly in patients with VOD. We conclude that alterations of the fibrinolytic system occur in patients undergoing BMT. Hypofibrinolysis seems to be at least one factor in the pathogenesis of VOD and the determination of PAI-1 might be helpful for diagnosing the disease. Our data also may explain the reported successful treatment of VOD by recombinant tPA. PMID- 7889008 TI - Total body irradiation and high-dose cyclophosphamide, BCNU and VP-16 (CBV) as a new preparatory regimen for allogeneic bone marrow transplantation in patients with advanced hematologic malignancies. AB - To increase the cure rate of advanced hematologic malignancies following allogeneic bone marrow transplantation we sequentially evaluated two intensified conditioning regimens. Eleven patients with acute myeloblastic leukemia (AML) beyond the first complete remission or chronic myelogenous leukemia (CML) not in first chronic phase received an association of 13.5 Gy of fractionated total body irradiation (TBI) followed by cyclophosphamide (CY) 120 mg/kg. Following this regimen, the probability of relapse was 47% at 3 years and the non-relapse mortality rate was 27%. Given the acceptable tolerance of this regimen, 13.5 Gy fractionated TBI was associated with intensified chemotherapy consisting of a combination of CY 120 mg/kg, carmustine 300 mg/m2 and etoposide 600 mg/m2 (CBV). This regimen was administered to 22 patients with comparable diseases. Of these patients, 7 received a transplant from a matched unrelated donor and 2 other patients received a second transplant from the original genoidentical donor. For 15 patients with a genoidentical donor, including the 2 second transplant, the 3 year probability of survival, disease-free survival and relapse are 40%, 40% and 14%, respectively. No regimen-related toxic deaths were recorded during the first 100 days. Of 7 patients with matched unrelated donors, 3 died before day 100, one death being directly attributable to the regimen. Early non-fatal regimen-related toxicity consisted mainly in grade II mucositis with no grade III or IV toxicity in recipients of genoidentical marrow. The late deaths were mainly due to chronic GVH-related complications. In conclusion, the association of fractionated 13.5 Gy TBI and CBV carries a high antileukemic activity and an acceptable toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889010 TI - Role of allogenic bone marrow transplantation in adolescent or adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma in first remission. AB - Sixty-nine adolescents and adults 15-51 years of age with untreated acute lymphoblastic leukaemia (ALL, 54 patients) or lymphoblastic lymphoma (LL, 15 patients) were referred for intensive antileukaemic therapy. Patients were treated according to one of two protocols. Both included induction and consolidation with vincristine, prednisone, daunorubicin, cyclophosphamide, Ara C and asparaginase. Fifty-eight patients achieved complete remission within 8 weeks of chemotherapy. One additional patient entered remission after allogeneic BMT. Altogether 86% of the patients achieved CR. Thirty-three patients are alive, corresponding to an actuarial survival of 48 +/- 6% at 5 years after start of therapy. Survival from time of achievement of CR is 53 +/- 7% at 5 years and disease-free survival (DFS) is 52 +/- 7%. Consolidation treatment was given to all patients except one. An HLA-identical sibling was identified for 30 patients (45%). Twenty-two patients were scheduled to be transplanted with marrow from an HLA-identical sibling. The survival and DFS in these 22 patients was 58 +/- 11% at 5 years. DFS was not significantly different compared with the DFS of the eight patients who received an auto-BMT and the 26 patients treated with maintenance chemotherapy. DFS at 5 years was 63 +/- 17% and 40 +/- 10%, respectively. We also evaluated the influence of the presence of an HLA-identical sibling on the treatment outcome of all patients alive 12 weeks after initiation of remission-induction therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889009 TI - Busulfan pharmacokinetics in bone marrow transplant patients: is drug monitoring warranted? AB - Pharmacokinetics were studied in relation to hepatic side-effects in 20 patients (19 adults aged 18-53 years and one child of 11 years) undergoing BMT after conditioning with 1 mg/kg busulfan (every 6 hours for 16 doses). Busulfan was quantitated in plasma samples at 10 time points within the 6 h dosing interval using HPLC before and after dose numbers 1, 2, 5, 13 and 14. For 13 patients data on all five doses are available; for the remaining seven patients three to four doses were studied. Mean maximum concentrations were 1512 ng/ml; mean trough levels for second and subsequent doses were 615 ng/ml. Maxima (Cmax) tended to be lower and times of maxima (Tmax) were later when busulfan was taken with a meal. Correlation of the area under the concentration versus time curve (AUC0-6h) between different doses was low within patients. In several patients problems with compartmental fitting of concentration data were observed mainly caused by the short dosing interval, which made estimates of T1/2 and model derived AUCs unstable. Three patients experienced hepatic veno-occlusive disease; kinetic parameters were not helpful in describing a particulate risk constellation for this subgroup. In our experience, the role of drug monitoring in this setting needs to be defined more clearly. PMID- 7889012 TI - Abundance of a restricted fetal B cell repertoire in marrow transplant recipients. AB - Patients undergoing bone marrow transplantation are humorally immunodeficient for one or more years post-transplant. This immunodeficiency could be partially caused by B cell repertoire restriction similar to that observed in ontogeny. To test this idea, the abundance of rearranged genomic segments bearing five variable heavy chain (VH) genes was compared in patients at several timepoints post-transplant and in immunologically normal neonates, infants and adults. The genes evaluated in the study (VH6, VH4-58p2, VH3-56p1, VH3-20p1 and VH3-13-2) were selected from those commonly utilized by fetal B cells. The assay employed quantitative PCR and oligonucleotide hybridization detection under conditions designed to detect relatively unmutated forms of these genes. In blood B cells from early post-transplant (2-5 months) patients, these VH genes were markedly overutilized compared with normal adults. B cells from late post-transplant (6-21 months) patients and from normal neonates and infants also overutilized these genes; however, to a lesser degree than early post-transplant B cells. The data suggest that, as in ontogeny, the B cell repertoire is strikingly restricted to fetal-type VH genes early post-transplant, and may become normal only very late (years) post-transplant. PMID- 7889011 TI - Autologous bone marrow transplantation using TBI and CBV for disseminated high/intermediate grade cutaneous non-epidermotropic non-Hodgkin's lymphoma. AB - Patients with stage IV high/intermediate grade cutaneous non-epidermotropic lymphoma of skin as first localization of the disease have a poor prognosis. In this setting, autologous bone marrow transplantation (BMT) has rarely been evaluated. We report here on the treatment of four patients with such lymphomas with autologous BMT using 12 Gy total body irradiation (TBI) and CBV (cyclophosphamide, carmustine and etoposide). Using a plexiglass screen, TBI delivered an homogenized dose to the skin. With this conditioning regimen, all patients are still in complete remission 22, 44, 46 and 51, respectively, months after high-dose chemotherapy, TBI and autologous BMT. PMID- 7889013 TI - Unusual infections following allogeneic bone marrow transplantation for chronic lymphocytic leukemia. AB - Unusually severe infections phenomena were observed in three patients with chronic lymphocytic leukemia (CLL) who had undergone allogeneic bone marrow transplantation (BMT) from matched sibling donors. The first developed three episodes of cytomegaloviremia requiring anti-viral therapy; the third episode accompanied by cytomegalovirus hepatitis which required prolonged therapy with foscarnet. Another had Listeria monocytogenes meningitis which was difficult to eradicate and required prolonged maintenance antimicrobial therapy with oral trimethoprim-sulfamethoxazole and intrathecal gentamicin until death due to chronic graft-versus-host disease. The third patient had cytomegaloviremia lasting 47 days, which did not clear within 4 weeks of full-dose ganciclovir. Although the number of patients is small, in our experience the problems encountered were unusually severe compared with patients allografted for other disease. We conclude that CLL patients undergoing allogeneic BMT may be at a higher risk of infectious complications than patients allografted for other diseases, and require careful monitoring. PMID- 7889014 TI - Pulmonary function and complications subsequent to autologous bone marrow transplantation. AB - Risk factors for early pulmonary complications occurring within the first 3 months after autologous bone marrow transplantation (BMT) were analysed in 158 consecutive adults. The long-term effects of autologous BMT on pulmonary function were analysed in 102 patients, who had survived free of disease for > 6 months after autologous BMT. Pulmonary function tests were performed before, at 6 and 12 months after autologous BMT and thereafter annually. The median follow-up was 12 (6-60) months. The incidence of early pulmonary complications was 16% (26 of 158). Idiopathic interstitial pneumonitis was seen in 11% of patients treated with total body irradiation (TBI). Single dose TBI was the major risk factor as regards early pulmonary complications but restrictive pulmonary disturbances and impaired diffusing capacity prior to autologous BMT were also significant risk factors. In both non-TBI and TBI-treated patients a mild restrictive ventilatory dysfunction and impaired diffusing capacity was noted 6 months after autologous BMT. In non-TBI-treated patients, these disturbances had resolved completely within 2 years whereas the lung volumes of TBI-treated patients were persistently reduced by 10% of their pre-autologous BMT values during follow-up. However, dysfunctions rarely progressed 6 months after autologous BMT. In most patients, ventilatory dysfunction was slight and had no clinical significance. PMID- 7889015 TI - Phase I study of high-dose busulfan, melphalan and thiotepa with autologous stem cell support in patients with refractory malignancies. AB - The purpose of this study was to determine the maximal tolerated dose of thiotepa administered with busulfan 12 mg/kg and melphalan 100 mg/m2 followed by autologous stem cell transplantation in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose busulfan 12 mg/kg, melphalan 100 mg/m2 and escalating doses of thiotepa 450-550 mg/m2 followed by infusion of cryopreserved autologous peripheral blood stem cells (n = 26) or marrow (n = 2). The maximum tolerated dose was determined to be busulfan 12 mg/kg, melphalan 100 mg/m2 and thiotepa 500 mg/m2. Two of three patients receiving thiotepa 550 mg/m2 experienced grade 3 colitis. Twenty patients were enrolled at the maximum tolerated dose and the incidence of grade 3-4 regimen related toxicity and mortality was 10% and 5%, respectively. Ninety-five per cent of patients experienced grade 1-2 mucositis, 50% grade 1-2 gastrointestinal toxicity, 35% grade I hepatic toxicity and 20% experienced grade 1-2 skin toxicity. The median time to achieve a granulocyte count of 0.5 x 10(9)/I was 10 days (range 8-20 days) and platelet transfusion independence was 10 days (range 1 26 days). Five of ten patients with stage 4 refractory breast cancer achieved a complete and two a partial remission with a complete response rate of 50% and a overall response rate of 70%. In conclusion, busulfan, melphalan and thiotepa can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy sensitive malignancies are warranted. PMID- 7889016 TI - Autologous bone marrow transplantation for childhood acute lymphoblastic leukemia in remission: first choice for isolated extramedullary relapse? AB - Between May 1984 and May 1992, 75 children 3-19 (median 9) years of age underwent autologous marrow transplant. Clinical data were obtained from the BMT Registry of the AIEOP (Italian Association of Pediatric Hemato/Oncology). Fifty-six children were transplanted after marrow +/- other site(s) relapse and 19 after an isolated extramedullary relapse. The transplant preparative regimens varied according to the center performing the transplant. Seven patients (9%) died of transplant-related complications. Forty-four (58.6%) of 75 patients relapsed again following autologous BMT. The 5-year DFS was 27.8%. An isolated extramedullary relapse was the only variable that statistically influenced DFS. In this retrospective study, autologous BMT for patients with ALL in second CR following marrow relapse did not offer an encouraging result (13% probability of DFS at 5 years), whereas autologous BMT following an (early) isolated extramedullary relapse resulted in nearly 70% DFS. Autologous BMT may be appropriate for this latter group of patients. PMID- 7889017 TI - Bone marrow transplant recipients harbor the B variant of human herpesvirus 6. AB - Lymphotropic herpesviruses have recently been isolated from patients undergoing kidney, liver and bone marrow transplantation (BMT). We have molecularly characterized isolates of HHV-6 from children undergoing allogenic BMT. We show that viruses recovered from the BMT recipients correspond to the B variant of human herpesvirus 6, the etiological agent of exanthem subitum. HHV-6 B strains are known to be associated with infections in the majority of children in infancy or early childhood. Infection in the BMT recipients most likely reflects the reactivation of these viruses during immunosuppressive treatment. Each of the reactivated viruses has its own characteristic heterogeneous (het) sequence. We show that the het sequence is stably unique for each HHV-6 strain. We also show that prolonged viremia can be documented with some of the patients, unlike the characteristic short duration febrile sickness in the exanthem subitum cases of infancy. The mechanism of HHV-6 B reactivation from latency is not known. Furthermore, the full clinical outcome of HHV-6 B viremia in the BMT patients requires further investigation. PMID- 7889018 TI - Successful treatment of chronic graft-versus-host disease with extracorporeal photopheresis. AB - A 43-year-old woman who had undergone allogeneic bone marrow transplant for chronic myeloid leukemia developed chronic GVHD. Despite cyclosporine A and low dose glucocorticoids and later concomittent PUVA-therapy, chronic GVHD with severe sclerodermatous manifestations including joint contracture and liver damage progressed. The Karnofsky performance score dropped to under 50%. Extracorporeal photopheresis (ECP) instead of PUVA-therapy was started. To our knowledge, we here report the first case of successful treatment of extensive chronic GVHD with ECP. PMID- 7889019 TI - Microangiopathic hemolytic anemia and renal impairment following autologous bone marrow transplantation: a case of hemolytic uremic syndrome? AB - Thrombotic microangiopathy, which encompasses both thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), is a severe and life threatening complication following bone marrow transplantation (BMT). It has been reported after allogeneic BMT but may also occur after autologous BMT. Here we describe a case of microangiopathic hemolytic anemia and progressive renal failure subsequent to autologous BMT. PMID- 7889020 TI - Successful vidarabine therapy for adenovirus type 11-associated acute hemorrhagic cystitis after allogeneic bone marrow transplantation. AB - A 36-year-old man underwent an allogeneic BMT for acute lymphoblastic leukemia. Eighteen days later the patient developed sudden onset of painful, gross hematuria due to adenovirus type 11 infection that did not respond to conservative therapy. There was an increase in serum creatinine levels and delayed recovery of the platelet count, associated with hemophagocytosis. After obtaining informed consent, vidarabine, which has been shown to be active against adenovirus in vitro, was started. The patient's symptoms improved within a few days of vidarabine therapy and urine cultures for adenovirus became negative. No serious adverse effects were observed. Vidarabine may be one therapeutic option in life-threatening adenovirus infection. PMID- 7889021 TI - Pharmacotherapy of congestive heart failure. Currently used and experimental drugs. AB - A survey is given of the currently used therapeutics in the treatment of chronic congestive heart failure. Symptomatic treatment is usually performed along the following lines: rest, sodium and fluid restriction to unload the decompensating heart, loop diuretics, angiotensin-converting enzyme inhibitors or other vasodilators; inotropic agents to improve the heart's mechanical performance; attempts to counteract the neuro-endocrine compensatory mechanisms, that is the activated sympathetic nervous and renin-angiotensin-aldosterone systems, as well as the rise in vasopressine levels. New insights have been obtained in the effects of cardiac glycosides, which are probably rather based on counteracting the elevated sympathetic neuronal activity than on their weak and uncertain inotropic action. Angiotensin-converting enzyme inhibitors are probably more effective than classical vasodilators owing to their additional interaction with the neuro-endocrine compensatory mechanisms. Ibopamine, a prodrug of epinine, appears to be rather a vasodilator and antagonist of the neuro-endocrine compensatory mechanisms than an inotropic agent. The most important clinical trials addressing the efficacy and adverse reactions to the various aforementioned therapeutics are discussed. New, experimental approaches in the drug treatment of chronic congestive heart failure include beta-blockers, calcium antagonists, vasopressin antagonists and inhibitors of atrial natriuretic peptide degradation. PMID- 7889022 TI - Comparative bioavailability study of two haloperidol decanoate containing products. AB - In our hospital pharmacy an injectable solution of haloperidol decanoate 141 mg/ml (equivalent to haloperidol 100 mg/ml) in sesame oil was prepared. The aim of this study was to prove bioequivalence of this formulation with the reference product, Haldol Decanoas. 15 schizophrenic patients, already stabilized with Haldol Decanoas, were enrolled. Intramuscular injections were given every three weeks in the following doses: 100 mg (1 x), 200 mg (7 x) and 300 mg (7 x). In this open, randomized, cross-over study all patients received four injections of the reference product, and four injections of the test product. Only after the fourth injection of each product (when steady-state levels were reached) a concentration-time profile of haloperidol was established during the dose interval of 21 days. The pharmacokinetic parameters AUC0-21 and Cmax were statistically evaluated. Based on these parameters the conclusion was drawn that both products were bioequivalent. The preparation of this injectable haloperidol decanoate solution in our hospital pharmacy amounts to an annual saving of approximately $39,000. PMID- 7889023 TI - Rectal administration of nicomorphine in patients improves biological availability of morphine and its glucuronide conjugates. AB - The pharmacokinetics of 30 mg nicomorphine after rectal administration with a suppository are described in 8 patients under combined general and epidural anaesthesia. No nicomorphine or 6-mononicotinoylmorphine could be detected in the serum. Morphine appeared almost instantaneously with a lag-time of 8 min and had a final elimination half-life of 1.48 +/- 0.48 h. Morphine was metabolized to morphine-3-glucuronide and morphine-6-glucuronide. These glucuronide conjugates appeared after a lag-time of 12 min and the half-life of these two glucuronide conjugates was similar: about 2.8 h (P > 0.8). The glucuronide conjugate of 6 mononicotinoylmorphine was not detected. In the urine only morphine and its glucuronides were found. The renal clearance value for morphine was 162 ml.min-1 and for the glucuronides 81 ml.min-1. This study shows that administration of a suppository with 30 mg nicomorphine gives an excellent absolute bioavailability of morphine and its metabolites of 88%. The lipid-soluble prodrug nicomorphine is quickly absorbed and immediately hydrolysed to morphine. PMID- 7889024 TI - Questions about drugs: how do pregnant women solve them? AB - In this study the need for information about drugs among pregnant women and the use of available sources was explored. The women participating in this study were well aware of the risks of the use of drugs. Health professionals were considered to be important sources of information and they should therefore use up-to-date information concerning this topic. Health professionals should also bear in mind in their counseling activities that the beliefs of pregnant women on the safety and need of drugs might lead to reasoned non-compliance. PMID- 7889025 TI - Stability of an oral midazolam solution for premedication in paediatric patients. AB - The objectives of this study were to assess the stability of a 1 mg/ml oral midazolam solution elaborated by our Hospital Pharmacy Service, and to confirm its clinical effect in presurgical paediatric patients. The solution's stability was tested by determining its pH and its UV-visible absorption spectrum at room temperature for up to 60 days. A high performance liquid chromatography method was used to confirm it. There was no significant change in pH value of either the test or a control solution. No loss of midazolam could be detected during the test. The Anaesthesiology Service assessed the sedation quality (very good, good, bad) and the venous puncture response, 20 minutes after the administration of 0.3 mg/kg of an oral midazolam solution. Twenty children were examined (age: 4-7 years). In addition, the haemodynamic and ventilatory functions were evaluated. PMID- 7889026 TI - "The trouble with the future... is that it is not what it used to be. PMID- 7889027 TI - Reliability of measurements of lumbar spine sagittal mobility obtained with the flexible curve. AB - Presently, there is no available scientific information that examines the interchangeability of tangent and trigonometric methods used to calculate measurements of sagittal mobility of the lumbar spine obtained with a flexible curve. Repeated measurements of the lumbar curvature were made with a flexible curve by using a standardized protocol on 10 healthy volunteers under three conditions: 1) standing, 2) sitting with maximum trunk forward bending, and 3) lying prone with maximum backward bending. Measurements were made by a team of two physical therapists working together; one therapist instructed the subject, and the other therapist performed the measurement. Agreement between the tangent and trigonometric methods was assessed graphically by plotting the difference between methods against the mean value of each pair of readings for each of the three conditions. Measurements differed by 4 to 7 degrees for each of the three positions of the lumbar spine. We believe such error is clinically acceptable and should not affect the clinical decision made on the basis of the measurement. PMID- 7889028 TI - The use of patient symptoms to screen for serious back problems. AB - Even when a patient is referred by a physician, the physical therapist must remain alert to the possibility that the patient may require medical care outside the realm of physical therapy. Physical therapists must be able to screen low back pain patients to identify those who have serious low back problems which require additional diagnostic evaluation and treatment by a physician. It is important for physical therapists to know which symptoms and signs or combination of symptoms and signs best indicate the likelihood of a serious problem. The purpose of this study was to test the sensitivity and specificity of low back pain symptoms in distinguishing individuals with a benign low back problem from those requiring surgical or medical intervention. Demographic and clinical data were collected retrospectively from a standardized low back pain questionnaire located in the medical records of 174 low back pain patients. Patients were classified as having a benign low back problem (N = 41) or a serious low back problem (N = 133) based on surgical findings or long term follow-up. Some individual symptoms had high specificity, but none had high sensitivity. To improve sensitivity while attempting to maintain moderate specificity, a number of symptoms were considered in parallel. The highest combination of sensitivity (.87) and specificity (.50) was obtained by combining in parallel the symptoms of unable to sleep, awakened and unable to fall back to sleep, medication required to sleep, and pain worsened by walking. PMID- 7889029 TI - A comparison of cervical rotation in age-matched adolescent competitive swimmers and healthy males. AB - Physical therapists routinely compare range of motion measurements with the opposite side and/or with a standard for "normal" range. However, "normal" range may vary in relation to the individual's occupational and recreational movement patterns. The purposes of this study were 1) to compare the range of active physiological cervical rotation in 14- to 17-year-old male competitive swimmers (N = 40) and controls (N = 40) and 2) to investigate the relationship between the freestyle stroke breathing pattern and differences in right and left cervical rotation in swimmers. Analysis of variance determined if a group difference existed in goniometric measurement of cervical rotation. The experimental group demonstrated a significantly greater mean range of total active cervical rotation right (p = 0.002) than the control group. Swimmers also demonstrated a significantly greater (p = 0.0002) range of rotation on their breathing side (mean difference of 5 degrees). It was concluded that the differences in physiological cervical rotation between swimmers and nonswimmers and between sides in the swimmers were influenced by the swimming activity. The clinician needs to consider the influence of activity when assessing range of motion. PMID- 7889030 TI - Mechanisms of neck and shoulder injuries in tennis players. AB - Shoulder injuries are common among athletes involved in repetitive overhead arm movements, particularly baseball pitchers and tennis players. Due to the similarities between pitching and serving, both athletes often present with similar types of shoulder injuries. However, subtle differences in neck and shoulder movements between the pitcher and tennis player may be responsible for additional mechanisms of injuries specific to tennis players. This paper outlines the similarities and differences between the pitch and serve and discusses how these differences may relate to additional neck and/or shoulder injuries specific to tennis players. In the analyses of mechanisms of injuries sustained by tennis players, such detailed analyses of movement patterns occurring during the serve may optimize a clinician's sports-specific rehabilitation protocol. PMID- 7889031 TI - Legal considerations in treating the injured athlete. AB - This article is intended to inform physical therapists about legal considerations impacting the practice of sports physical therapy. Our objective is to generate an awareness of these issues to enhance the quality of physical therapy provided to injured athletes and to minimize potential legal liability. Three areas in which physical therapists who treat injured athletes need to be particularly careful are: 1) providing treatment designed to enable continued play with an injury before it is fully healed, 2) informing an athlete of the potential health risks of continued athletic activity in his or her physical condition, and 3) evaluating and advising an athlete concerning his or her ability to resume athletic activity. Based on the parallels between industrial rehabilitation and sports physical therapy, the authors propose that consensus objective criteria and guidelines should be established to assist therapists in advising referring physicians and athletes whether return to play is appropriate under the circumstances. PMID- 7889032 TI - Outcome comparison of workers' compensation and noncompensation low back pain in a highly structured functional restoration program. AB - Low back pain is both common and costly. A paucity of information exists within the literature comparing workers' compensation and noncompensation back-injured individuals. The intent of this study was to examine differences between the two groups--individuals injured and seeking compensation, and injured individuals not pursuing a compensation claim. Sixty subjects referred to a functional restoration facility were identified and evaluated, and their progress was tracked. Demographic and return-to-employment data were collected. Of the 35 workers' compensation subjects, 23 (65.71%) were not working during therapy, while only one of 25 noncompensation individuals was not working throughout treatment. Thirty-two compensation individuals (91%) and all of the noncompensation group members made successful returns to employment (p < or = .05). The authors conclude that while some differences existed between the two groups, a high return-to-work frequency was achieved (91%) (p < or = .05). Results indicate high success outcomes as measured by return-to-work, increased function, and reduced pain. These outcomes were obtained through highly structured, medically supervised functional restoration programs. PMID- 7889033 TI - Haemolytic anaemia in ruminants fed forage brassicas: a review. AB - This paper describes the present state of knowledge on metabolic disorders caused by the intake of forage brassicas, particularly the cellular and molecular changes leading to haemoglobin oxidation and precipitation as Heinz-Ehrlich bodies and to haemolysis. The factors responsible for variations in the haemolysis severity are then discussed as well as the measures for preventing pathological risks. Emphasis is placed on the identification of topics which need increased research activity. PMID- 7889034 TI - Pathobiology of bovine leukemia virus. AB - Bovine leukemia virus (BLV) is a retrovirus similar to the human T-cell leukemia virus (HTLV). Most BLV infected animals (70%) develop a B-cell lymphoproliferative syndrome with altered productive traits and 1 to 5% die with B-cell lymphosarcomas. Although BLV infection is world-wide, western European countries have almost eradicated it by slaughtering the seropositive animals. BLV infection remains endemic in many countries including the United States and prophylactic strategies involving recombinant vaccine vectors, genetically modified BLV and transgenic animals resistant to the infection are under study. PMID- 7889035 TI - Variability in susceptibility to anthelmintics of the lungworm Muellerius capillaris first-stage larvae. Relationship to dairy-goat farms and previous exposure to febantel treatment. AB - Seven dairy-goat farms, located in central, western France, were studied in order to assess the variability in susceptibility of the lungworm Muellerius capillaris first-stage larvae (L1) to 3 different anthelmintics in relation to farm origin, by means of motility tests. The motility tests were performed by mixing larval suspensions with pyrantel (PYR), thiabendazole (TBZ) or ivermectin (IVE) solutions (3 concentrations x 3 incubation durations). The same anthelmintic tests were repeated 7 and 21 d after febantel (probenzimidazole) treatment of the goats. Before the treatment of goats, the average ratio (x 100) of L1 motility compared with control were very different for the 3 anthelminthics: 44, 30 and 59, respectively for TBZ, PYR and IVE. The ratios of L1 motility were the same at days 7 and 21 after the treatment of goats. The susceptibility of L1 to anthelmintics varied a great deal from 1 farm to another when goats had not been previously treated, whereas L1s from the same farms were the same after treatment of goats. The occurrence of different motilities of L1 with the anthelmintic tests from 1 farm to another should be related to the existence of different populations of M capillaris. The L1 motilities were reduced after anthelmintic treatment of goats suggesting a temporary effect on populations of M capillaris females shedding L1. PMID- 7889036 TI - Early haematological and pathological abnormalities of pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV). AB - Twelve 8-12-week-old specific-pathogen-free (SPF) cats were inoculated intraperitoneally with feline immunodeficiency virus, or with blood from inoculated cats. Three cats of the same age were used as controls. All animals were sacrificed 10 weeks after inoculation. The inoculated cats seroconverted between the 3rd and 6th weeks after inoculation. For 6 infected cats, a decrease in the CD4/CD8 lymphocyte ratio was observed as early as the 6th to the 10th week after inoculation. Granular lymphocytes and atypical cells with cytoplasmic vacuoles and very irregular nuclei were observed in the blood from the 1st to the 10th weeks after inoculation. The only statistically significant differences were obtained 10 weeks after inoculation. Mean leucocyte and lymphocyte numbers were decreased (8000 and 3200 per microliter respectively compared with 14500 and 7200 per microliter before inoculation). The mean CD4/CD8 ratio was also decreased (from 2.60 to 1.50). The percentage of lymphocytes in the bone marrow was increased, reaching 34% as a mean for infected cats as opposed to 20% for control animals. The atypical cells found in the blood were not observed in the marrow. The sternebral bone marrow did not contain lymphoid follicles, as described for HIV infection. Severe follicular hyperplasia was only found in the lymph nodes, but no viral particles could be observed in them. PMID- 7889037 TI - Madin Darby bovine kidney cell synchronization by lovastatin: application to bovine herpesvirus-1 gene expression. AB - The number of investigations involving cell proliferation has increased rapidly in the last years. One of the major difficulties in studying cell-cycle-related events is obtaining highly synchronous cell populations without metabolic imbalance. This study demonstrates that the Madin Darby bovine kidney (MDBK) cells, a commonly used cell line in veterinary research, can be effectively synchronized using lovastatin (Lov), a drug used to treat hypercholesteremia in humans. This was demonstrated by the following results: (i) Lov inhibits cell proliferation in a dose-dependent manner; (ii) Lov synchronizes MDBK cells mainly in the G1 and secondarily in the G2+M cell-cycle phases; (iii) the cytostatic effect of Lov can be specifically inhibited by addition of mevalonate (Mev) (Lov inhibits the synthesis of Mev); (iv) removal of Lov from G1-arrested cultures, followed by addition of Mev, resulted in the synchronous recovery of DNA synthesis; and (v) 5-bromo2'-deoxyuridine incorporation experiments revealed that MDBK cells synchronization by Lov can be followed for at least 3 cycles after removal of Lov and addition of Mev. Furthermore, as an application of investigations based on the availability of synchronized MDBK, we showed that bovine herpesvirus-1 gene expression is independent on the cell cycle. PMID- 7889038 TI - Kinetics and haematological effects of erythropoietin in horses. AB - A plasma kinetic study of erythropoietin (EPO) was carried out in 4 horses after subcutaneous administration (30 IU/kg bwt) of recombinant human erythropoietin (rhEPO). At standardized intervals for 48 h before injection and for 60 h post administration, the EPO plasma levels were determined with an immunoradiometric assay based on a sandwich technique. The peak plasma concentration (30-113 mIU/ml) was observed after a delay ranging from 6 to 9 h post-administration and the drug levels reached a physiological value around 60 h following rhEPO injection. Moreover, reference values for plasma EPO concentrations, which were separately determined in 70 racehorses and 34 sport equines, ranged between 0 and 9 mlU/ml. After drug administration, no significant variations in red blood cell count, haemoglobin concentration, haematocrit or mean red blood cell volume were observed in the 4 animals. Further, minimal variations in these parameters were detected in a horse which received three 120 IU rhEPO/kg bwt doses successively. Therefore, high rhEPO doses are probably required to induce a visible haematological effect in equine species. PMID- 7889039 TI - Obtention of ovine IgE from heterohybridoma. AB - Mesenteric and bronchial lymph node cells from sheep immunized with Ascaris suum antigens in combination with Bordetella pertussis vaccine were fused with mouse myeloma cell lines, P3-X63-Ag8.653, NSO.U and NS1.1.Ag1.1. One heterohybridoma cell line (NS1.1.Ag1.1 x sheep) producing ovine immunoglobulin E was detected by the passive cutaneous anaphylaxis test. PMID- 7889040 TI - Molecular biology tools in parasitology: their use for identification, biosystematics and population genetics. Orleans, France, 23-25 March 1994. Abstracts. PMID- 7889041 TI - Ureteral obstruction associated with prostate cancer: the outcome after ultrasonographic percutaneous nephrostomy. AB - We retrospectively reviewed the outcome of 28 prostate cancer patients with ureteral obstruction treated by percutaneous nephrostomy. The over-all survival was 60% at 1 year and 32% at 2 years. The 1 and 2 years survival rates of 13 patients with no prior hormonal therapy were 70 and 45%, respectively, while those of patients who had previously received hormonal therapy were 46 and 17% respectively. Of 10 patients who had severe renal failure before percutaneous nephrostomy (serum creatinine greater than or equal to 7 mg per dl), 8 had an adequate return of renal function (serum creatinine less than 3 mg pe dl) after drainage and 55% survived more than 1 year, cutaneous nephrostomy is safe and effective in relieving ureteral obstruction and reasonable survival can be achieved even in patient with renal failure. Percutaneous nephrostomy should be considered strongly in these patients. PMID- 7889042 TI - [Role of color-Doppler in the assessment of erectile impotence: personal experience]. AB - We present our experience with colour duplex sonography in the assessment of 38 impotent men, whose ten underwent radical prostatectomy, following intracavernous pharmacological stimulation with PGE1. All patients with a clinical good response following PGE1 injection had peak cavernosal artery velocities > 30 cm/sec. The remaining suboptimal responders who presented an elevated end-diastolic velocity (> 5 cm/sec) showed a venous leakage demonstrated with cavernosography. Colour duplex sonography is a valuable and non-invasive tool in the assessment of impotence and can provide valuable information in the diagnosis of vasculogenic erectile dysfunction. PMID- 7889043 TI - [Ultrasonography diagnosis of medical nephropathies: the clinician's needs]. AB - Echography and echo-color Doppler represents a relatively new tool in the management of patients with renal disease. We report here the flow-chart we currently use to evaluate such patients, and emphasize the role of echography and of echo color Doppler in diagnosing and monitoring medical renal diseases. Besides gaining informations on renal morphology and texture, echo color Doppler provides clinically relevant data on blood flow and vascular resistivity. Changes of these variables are useful in the differential diagnosis between functional and organic acute renal failure. In addition, as histology remains essential in diagnosing parenchimal disease, echography has a role, allowing guided biopsy, safer approach, and monitoring of possible complications. Finally, when diagnosis has been obtained and therapy has been started, echography is useful in monitoring long term changes of size, texture and blood flow. PMID- 7889044 TI - [Validity of superficial echography in the study of urethral pathology]. AB - In male patients routine examination for urethral disease includes retrograde and anterograde urethrography and urethroscopy. In the patients underwent radical cystectomy, detection of cancerous cells in the urethral washing suggest cancer relapse. Nowadays we can achieve a sonographic study of the anterior male urethra, using a superficial high frequency ultrasound probe. Since September 1992 till July 1993, 12 patients underwent cystectomy at our Institution and 13 patients affected by urethral stricture, have been investigated by routine examination and sonographic urethrogram. In the first group of patients, out of 3 patients with urethral tumor, sonourethrography has confirmed the presence of tumor in 2 cases. In these second group of patients, sonourethrography has located the stricture, evaluated the length, calculated the diameter of the stricture and the depth of fibrosis. Sonourethrography is a non-invasive method that can provide valuable information about the urethral lumen and the urethral wall. PMID- 7889045 TI - [Dynamic renal echography versus urography in the follow-up of patients who have undergone ureterosigmoidostomy]. AB - The main post uretero-sigmoidostomy complications are stricture of the anastomosis, chronic infection and urolithiasis. In our institution the patients with ureterosigmodostomy undergo a follow-up protocol in which blood chemistry, ultrasonography, intravenous pyelography and C.T. are periodically performed. The aim of the present paper is to compare the accuracy of kidney sonography after diuretic stimulation with intravenous pyelography in the diagnosis of ureteral stenosis. Out of 91 patient with ureterosigmoidostomy 18 patients (34 kidneys) underwent intravenous pyelography, a basal U.S. and then a dynamic one at 5, 10, 15, 30, 45, 60, 90, 120 minutes after administration of furosemide 20 mg i.v. At basal U.S. 27 kidneys were normal and 7 showed a dilations. After diuretic stimulation we observed 16 normal kidneys, 16 dilated units and 2 intermittent hydronephrosis. Out of 16 dilated kidneys 6 became normal in 60 minutes. Out of 10 dilated units 3 were normal in 90 minutes (hipotonic), 2 were normal before 120 minutes (low grade obstruction) and 5 were dilated after 120 minutes (high grade obstruction). With intravenous pyelography we observed 27 normal kidneys and seven dilated units. Dynamic sonography have shown high sensibility (100%), specificity (88.8%) and accuracy (91%) in diagnosis of ureteral obstruction in to I.V.P. in the follow-up of this kind of divesion. PMID- 7889046 TI - [Usefulness of echography in the diagnosis of urachal cancer]. AB - Authors report a case of urachal carcinoma diagnosed with ultrasonography linear probe 7.5 mhz. With this work they want underline the importance to use a superficial probe in all those situation in which the sonography shows a neoformation in the posterior wall of the bladder; it should be the spy of a urachal neoformation. PMID- 7889047 TI - [Role of micturitional transrectal echography in the diagnosis of obstructive bladder neoplasms. Clinical case]. PMID- 7889048 TI - [Semeiotic flowmetry in complex varicocele]. AB - The Authors report on their specific experience on the funicular Doppler veocimetry, regarding the varicocele. In particular we enhance the semeiological spects of the C.W. Doppler velocimetry in the sub-clinical varicocele, in the bilateral one and in the characterization of the spermatic and cremasteric refluxes, and of the external pudenda vein. The Authors stress the utility of the definition of the amount of the reflux, so achieving an integration with the existing classification by degrees, that as it is now days expressed, it seems, to regard the elapsed time and the quantity of reflux caused by the Valsalva manoeuvre. In the practical velocimetry those elements have not been proved to have a parallel increment. Lastly, we report on some cases of veno-spermatic refluxes, uniquely observed in the clynostatism, along with a missing orthostatism. Moreover the Authors believe that some of these hemodynamical consideration could be revisited. PMID- 7889049 TI - [Urologic applications of intralaparoscopic echography]. AB - The impossibility to palpate organs and tissues is probably the most important drawback of the laparoscopic approach: laparoscopic sonography represent the only real alternative to manual palpation. The laparoscopic approach in the field of urology was initially limited to the identification of the undescended testes in paediatric urology and to the laparoscopic ligation of varicocele. More recently, it took into account the pelvic lymphadenectomy for staging prostatic and bladder cancer. The upper urinary tract and the retroperitoneum were approached more recently. In a preliminary phase the indications for laparoscopic nephrectomy were limited to benign diseases, such as atrophic kidney in patients with renal hypertension, and scarred pyelonephritic kidney. At present some preliminary experiences are reported about nephrectomy performed for carcinoma of the urether or of the upper collecting system and for renal masses of unknown origin. Another indication for a laparoscopic approach to the kidney is represented by symptomatic renal cysts. These cysts have been usually treated with percutaneous aspiration and/or sclerosis, but a high rate of recurrence is reported. Laparoscopy may be used to approach renal cysts with the advantage that most of the cystic wall could be excised, reducing the change of recurrence. Another possible indication for laparoscopy and laparoscopic sonography is the retroperitoneal lymphadenectomy in testes cancer with staging or therapeutic purposes. Nowadays preliminary experiences in laparoscopic adrenalectomy have been reported in a limited series of cases. In this report the Authors present their initial experience using a 7.5 MHz rigid probe having 400 crystal which can be inserted into a 10 mm trocar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889050 TI - [Role of echography in the diagnostic-therapeutic management of renal cysts]. AB - Herein we report on the results of 171 out of 214 patients with renal cysts. In 127 cases diameter of cyst being less than < 6 cm, was monitored repeating renal ultrasound every 6 months: 78 patients underwent pecutaneous cyst echoguided puncture, while 9 patients were treated as follows: 4 by open surgery, 3 by laparoscopy and 2 by percutaneous treatment in general anaesthesia. Cysts are classified in 4 types and therapy is different according to Bosniak's classification. When the cyst is less than 6 cm in diameter and symptomatology is absent, we follow the patients up with yearly ultrasound. In our experience cyst sclerotization is carried out by injecting either ethanol or Trombovar or 50% glucose in water alone or associated with 2% Aethoxysclerol. The best results are obtained from the use of ethanol (30% of the volume of cyst). However some relapses are encountered after this kind of procedure. In these cases it is helpful to examine the cystic wall because of the presence of intracystic septa. Percutaneous treatment by means nephroscopy permits to visualize the cystic wall but it is not able to perform a biopsy of its wall. Laparoscopic treatment is performed by inserting 5 trocars with the patient under general anaesthesia. This technique is able to localize and biopsy the cystic wall without causing side effects or complications. Open surgery was performed only in 4 patients affected with hidatid cyst. At present echoguided cyst puncture permits to approach the renal not complicated cysts, while laparoscopy constitutes a safe treatment in the case of benign recurrent and complicated cysts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889051 TI - [Renovascular hypertension: possibilities of echo-color Doppler]. AB - The evaluation of blood flow at the level of renal arteries by echo-Doppler may be useful in detecting a stenosis in patients affected by arterial hypertension. We studied 33 subjects with arterial hypertension using the most suitable scansions to visualize renal arteries. The measured parameters (R.I. and Vmax) resulted to be higher than normal range in 7 and 1 patients respectively. Then these patients underwent renal scintigraphy and arteriography; in 3 of them the presence of a stenosis of a renal artery was confirmed. Therefore the echo Doppler study of renal arteries, even if has some shortcomings due to technic troubles, revealed to be a useful tool in the screening of hypertensive patients to support the other tools already used to this aim. PMID- 7889052 TI - [Physiopathology of the pelvic elements of support in stress urinary incontinence in women]. AB - Stress urinary incontinence (SUI) is called as the involuntary loss of urine without the presence of detrusor contraction with bladder pressure that is higher than maximum urethral pressure. The SUI may be caused either by hypermobility of urethra or by inefficacious intrinsic urethral sphincter activity. It is clear that female urinary continence is established by the balance of opposed forces in the pelvis. The elements that contribute to the maintenance of continence are: 1) maximum urethral closure pressure; 2) anatomical and functional length of urethra; 3) ability of perineum to increase the urethral pressure simultaneously with the Valsalva's manoeuvre; 4) appropriate localization of the sphincteric unit. The alteration of the above-mentioned elements may be caused from no functionally of pubo-urethral ligaments and the laxity of cardinal ligaments and of pubic-cervical fascia. PMID- 7889053 TI - [Physiopathology of bladder-sphincter dysfunctions]. AB - Bladder voiding implies activation of mictional reflex. The coordination of the latter is strictly dependent on center of miction situated in encephalo. The interruption of the nervous fibers linking pons with center of miction situated in sacral spinal cord causes the appearance of vesico-sphincter dyssynergia. On the contrary, the interruption of the fibers localized above the opns causes the loss of the voluntary control of miction. Finally the lesion of sacral spinal cord or of the nervous fibers connected with it is responsible for the appearance of detrusor areflexia with reduction of the smooth sphincter activity and paralysis of the striated one. PMID- 7889054 TI - [Role of diuretic dynamic echography in the study of the pyelo-ureteral junction: review of a caseload after the first 4 years of experience]. AB - Diuretic ultrasound, described in Literature in the seventies from Rosenfield, is an effective technique if compared with the functional urodynamic study and the diuretic renography evaluation for the assessment of upper urinary tract obstruction. In our study we have compared the effectiveness of diuretic ultrasound with diuretic intravenous urography in the evaluation of obstructive pathology of ureteropelvic junction. The technique was performed on 47 patients 11 of whom were pediatrics making a total of 94 renoureteric units. Results show high sensibility of this technique either with severe obstructions (94%) or moderate obstructions (96%). PMID- 7889055 TI - [Current utilization and potential developments of echography in the urologic field]. AB - The employment of ultrasonography in urology is not well established yet. On this purpose a survey of present situation in different medical setting was conducted. 200 questionnaires were filled by about 1000 physicians operating in various medical centers. The most of answers was provided by assistant head physicians (41%) and head physicians (30%), with a clear prevalence of urologists (64%) and nephrologists (32%). The number of beds reported by each centers ranged from 0 to 90, while the average doctor-patient ratio was 3.6. 72% he centers could avail of B-mode echography (22% of them owned an echo-Doppler velocimeter). The data obtained reveal the great heterogenety of present medical system and the necessity of finding a correct equilibrium between specialistic and primary care settings. It can be concluded that the correct use of ultrasonography depends both on good knowledge of its real indications and on the proper professional training of the echografist. PMID- 7889056 TI - [Urethral diverticuli in women: role of diagnostic methods in the preoperative assessment]. AB - From 1985 to 1993 we observed 9 female patients with urethral diverticula. All patients underwent first clinical examination and then US (suprapubic and transrectal or transvaginal scans) and X-ray cystography which demonstrated the communication between the diverticula and the urethra, MRI was also performed, in order to explain the rapports between the diverticulum and the sphyncter. All patients underwent surgery and 8 were cured. No cases of incontinence were observed. PMID- 7889057 TI - [Locally advanced prostatic cancer and systemic involvement]. AB - In a group of 115 patients with prostatic cancer, the correlation between the local and systemic evolution of the neoplasm has been evaluated. In 80 patients non local and systemic up-staging of the tumor was observed. In further 18 patients both local and systemic staging uppers and in the remaining 17 patients no correlation between local and systemic evolution was observed. In conclusion, in this series, the prostatic cancer demonstrated an high concordance in both local and systemic evolution and then the modifications of local staging can be used as a predictive parameter of systemic evolution of the prostatic cancer. PMID- 7889058 TI - [Echographic features of testicular neoplasms. Our experience]. AB - 14 patients with primitive testicular cancer underwent US and afterwards surgery. A comparison between echo-pattern and hysto-pathology was done with the following results: sharp limits and ipoechoic homogeneous pattern in leydigioma and low staging seminoma. Presence of anechoic areas and irregular limits: teratoma and embrionary carcinoma with no correlation with the staging. Inclusively no correlation between echo-pattern and staging of neoplasm or presence of neoplastic lymphnodes was observed. PMID- 7889059 TI - [Urethral diverticuli in patients with spinal cord injury: echographic study]. AB - Urethral diverticula, a not infrequent complication in patients with spinal cord injuries, usually involve the bulbous urethra which is particularly exposed to the trauma of catheterism. Indeed, the frequent association of urethral trauma and infection is often the cause of diverticula in these patients. Diagnosis is made by ascending urethrogram, voiding cystourethrogram and urethroscopy. Eight patients between 20 and 45 years of age with spinal cord injuries who had used an indwelling catheter for periods ranging from 1 to 18 months and who presented urethral diverticula at conventional investigation, underwent transperineal and penile contact ultrasonography using 3.5 and 7.5 MhZ real-time scanners. Ultrasonography was performed during intraurethral injection of saline solution through a catheter positioned near the external urethral meatus. Before the scan all patients had undergone a neuro-urological physical examination, urine analysis and culture, renal and bladder ultrasonography, ascending urethrogram and voiding cystourethrogram, urethroscopy and urodynamic investigation. Ultrasonography identified all urethral diverticula, defined them morphologically, visualized the diverticula filling and emptying phases and evaluated urethral wall and periurethral tissue characteristics, without exposing patients to any dangerous gonadal irradiation. Ultrasonography cannot replace radiological investigation but is a valid alternative in cases of contrast medium allergy, when monitoring inoperable diverticula and in postoperative follow-ups. PMID- 7889060 TI - [The clinician's need in renovascular hypertension]. AB - Clinician questions in nephrovascular hypertension are: 1) Is hypertension secondary to nephrovascular disease? 2) Is vascular obstruction susceptible of surgical management? 3) Which is the best technical approach? In this review of recent international literature we have focused diagnostic value of echo-color Doppler in the screening of patients with secondary hypertension. The sensibility and specificity of this diagnostic test reach 89% and 99.5%. Respectively when the stenosis is over 70%. Anyway when the stenosis is under 70% the accuracy of this examination is lower. Angiography remains the gold standard test in patient eligible for surgery, although its invasiveness. Diagnostic tests of the renin angiotensin axis (e.g. Captopril test) are useful too, but morphologic evidence is not provided. Surgical approach is the best choice in elective patients. PMID- 7889061 TI - [Non-surgical treatment of urethral fistula: a suggested technic]. AB - The urethral fistulas need for recovery the traditional surgical approach. Recently are available for surgeons substances and devices particularly compatible with biological tissue and very safe. We have taken advantage of this good opportunity to treat an old and multiple fistula of the urethra in the perineum. We are completely satisfied of this, alternative method that lead the patient to recover, avoiding in the same time the risks of another surgical operation too, that is difficult and complicated. PMID- 7889062 TI - [Echo-guided retropneumoperitoneum in laparoscopic renal surgery]. AB - Laparoscopic surgery admits the retroperitoneal approach: the main restriction is the tight manoeuvring space that can be obtained with insufflation. The use of a dilatator balloon in the retroperitoneal cavity offers a solution to this problem. A cutaneous access and a dull parietal path is created, with blind positioning of the apex of the dihedron between the inferior renal pole and the ureter. Peroperative ultrasound control makes it possible to identify the inferior renal pole, to control the position of the apex of the catheter with the balloon and the movements of the retroperitoneal organs in real time. The possibility of following the procedure by ultrasonography have proven usefull in our experience. PMID- 7889063 TI - [Imaging follow-up of orthotopic ileal neobladders++]. AB - In the follow-up for new urinary reservoirs created from the ileum in the orthotopic position, study by imaging plays a fundamental role The routine radiological examinations for monitoring patients with surgically created orthotopic bladders comprise M.R., C.T., urography, cystography and transrectal ultrasonography (U.S.). By means of these examinations, it is possible to evaluate the ureter-neobladder anastomosis, the capacity of the reservoir and the urethra-neobladder junction. Trans rectal U.S. is of particular importance, providing information on the new neck, the critical point of this new type of urinary diversion. 90 patients with new orthotopic ileal neobladder by Studer were examined. The image investigation in these patients subjected to total cystectomy for cancer, with preparation of a new orthotopic ileal neobladder by Studer, was shown to be indispensable in detecting both of disease and the behaviour of the upper urinary tract following these current urinary diversion. PMID- 7889064 TI - [Echo-color Doppler in acute scrotum]. AB - The Authors report their experience about the use of color doppler US in the diagnosis of acute scrotal pain. Their data show the importance and the central role of color Doppler US to distinguish between phlogosis and ischemia. PMID- 7889065 TI - [Treatment of voluminous renal cysts with drainage and repeated percutaneous administration of alcohol. Our experience]. AB - The Authors report their experience on the treatment of simple voluminous renal cysts with an echo-guided puncture followed by a sclerosis, that is repeated thrice, with an endocavitary injection of pure alcohol. Since the fair results (94% of success) that were obtained after a mean follow-up of 16 months, the low invasivity of the method and the benignity of the disease, should propose the method itself as the first approach for the treatment of voluminous but not complicated renal cysts. PMID- 7889066 TI - [Endoscopic treatment of sphincter insufficiency with autologous fat injection]. AB - A total of 11 women with stress urinary incontinence related to intrinsic sphinteric incontinence (type 3) underwent periurethral injection of autogolous fat. The fat was harvested from the abdominal wall by special liposuction unit including: a special syringe for plastic surgery provided with 6 straight needles 12-20 Gauge connected to a vaum extractor for the liposuction; a 14 Gauge straight needle for lipofilling periurethrally and then a cystoscope with a 0 degree and 70 degree lenses. The fat is injected at 3 and 9 o'clock position and the mean quantity was 15,5 ml. The exact localization of the injected area was endoscopically detected before, and afterwards with an ultrasound transrectal probe. Follow up results were assessed clinically and by urodinamic and ultrasound evaluation at 3, 6 and every six months following. A follow up was ranged from 9 to 36 months (mean 22.6). Of the 11 women, 6 (54.5%) were cured, 2 (18.2%) pats. Were improved and in 3 woman (27.3%) no change occurred. The Urodynamic parameters didn't show any statistical significant change except for Functional Urethral Length (p < 02) and Flow Time (p < 04) that increased in cured patient. The ultrasound evaluation showed an hyperecogenic aspect in all patients; and al the urethral wall was hyperecognic in 1 woman. The resorption average time was 8 months, and 8 pats (72.7%) showed a partial resorption after 22 months. 3 patients should have been reinjected, 2 of them were cured and in the last one an improvement was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889067 TI - [Echographic diagnosis and treatment of urethral instability]. AB - Unstable urethra as defined by the International Continence Society is the condition where loss of urine is caused solely by a fall in urethral pressure. But the condition is rare and therefore the term Urethral Pressure Variations (UPV) is better used. The UPV are caused by activity of smooth and striated muscles. Frequently is associated with Genuine Stress Incontinence or Detrsor Instability that can make worse urinary loss. An urogynecologic work-up can reveal the presence of UPV by Urodynamic and ultrasound evaluations. The Urethral Pressure monitoring reveals the fast or slow intraluminal pressure fall between 10 to 20 cm H2O or more. The ultrasound examination carried out by a linear vaginal probe (5 MHz) can observe the contraction of the "prepubic muscle" (anterior pubo-urethral ligament + bulbo-spongious muscle) as a preliminary phase of urethral pressure fall. The prepubic muscle located from clitoris to the external meatus exert a force on the anterior and distal part of the urethra during the intraluminal pressure falls. With the section of this structure (muscle + ligament) we treated 9 patients diagnosed as having UPV with concomitant irritative urologic symptoms. Out of 9 women with a follow-up ranged from 1 to 23 months (mean 9,5), 5 patients (56%) were cured, 2 (22%) of them were improved, in the last 2 (22%) patients no change was observed. The complications were minimal only a vestibulo-vaginal increased sensitivity, and one case of dyspareunia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889068 TI - [Echographic monitoring of follicular growth]. AB - The sonographic monitoring of the ovarian follicular growth has been widely adopted, being a non invasive method, easily repeatable, well tolerated by the patient and low cost. A further impulse has been obtained by the endovaginal sonography. During a natural menstrual cycle the sonography can highlight the alterations that occur to the follicle and to the endometrium, supplying useful information on ovulatory timing. In pharmacologically induced menstrual cycles, the sonography enables us to evaluate the ovarian response to the therapy in tennis of number, size, site, and the type of growth of the recruited follicles, enabling us therefore to modulate the stimulation according to the individual response. Fluximetric studies are among the new applications the most promising, since they allow us not only to identify quickly the vascular structures, but also to supply a predictive value for the embryo implantation and the pregnancy evolution. The sonography at present proves to be irreplaceable in assisted reproduction programmes. PMID- 7889069 TI - [Echography in assisted reproduction techniques]. AB - The Authors describe the A.R.T. echoguided techniques, that can be routinely used in IVF/ET programs. All these techniques are simple and have replaced the previous ones. The echoguided oocyte recovery is now widely accepted instead of the laparoscopic way: the gamete intrafalloppian transfer can be easily performed under local anesthesia; the selective fetal reduction in cases of multiple pregnancies can be easily carried out on an outpatient basis. PMID- 7889070 TI - [Echography in prostatitis]. AB - In many infertile patients abnormalities in sperm are due to prostatic inflammatory disease. In the male reproductive system temporary episodes of inflammation, caused by newly discovered micro-organisms such as Chlamydia Trachomatis and Ureaplasma Urealyticum, may occur frequently and cause sub clinical inflammation. This rapidly became chronic and induce the development of anti-spermatozoon antibodies. This latent clinical pattern and lack of symptoms often means diagnosis is late and medical treatment inadequate. In recent years attention has been focused on transrectal ultrasonography as a possible gold standard for diagnosing prostatic inflammatory disease. Widespread use of technologically advanced instruments has significantly improved the quality and definition of prostatic images. This paper discusses the current role of transrectal ultrasonography in the diagnosis of prostatic inflammatory disease. Abnormalities in the ultrasound pattern, caused by infection, are analyzed in detail and discussed critically in order to assess their role as markers of prostatic inflammation. PMID- 7889071 TI - [Echohysterography in the diagnosis of female sterility: preliminary results]. AB - Couple's study infertility sometimes need repeated hysterosalpingographical evaluations. In three cases the A.A. value echohysterosalpingography's utility. The echohysterosalpingography gives morphological and functional dates, is easy repeatable and the patients aren't exposed to ionizing radiations. PMID- 7889072 TI - [Urethral echography: potential and limitations]. AB - Since in the early years of 1980, the diagnostic for images about male's urethral injury was exclusively assigned to urethrocystography. Sially in repeated check the gonads too often are exposed to ionizing radiations. Our results show urethrocystography/ultrasonography good correlation (13/15) cases) with 86% sensibility. Even if the urethrocystography is a methodic of first instance, the urethral ultrasonography is efficacious in follow up of urethral injury, particularly in the study of anterior urethra. PMID- 7889073 TI - [Echographic characteristics of calcifying fibrous pseudotumor of the epididymis]. AB - Calcifying fibrous pseudotumor of epididymis is a rare neoplasia. The A.A. report echographical aspects about two clinical acses examined in 1993. Peculiar aspects of tumour are characterized by acoustic obstruction of the fibrous tissue and contextual iperechogenic spots, so to stimulate a calcific pseudocapsula. The A.A. revalue the echographical images after surgical exploration and discuss about differential diagnosis with TBC. PMID- 7889075 TI - [Role of echography in neoplastic priapism]. AB - The author, observing one case of neoplastic priapism, poiting on the role of ultrasonography in this disease. Its easy and quick execution, the possibility to repeat it, its low cost, its diagnostic sensibility in evaluating the infiltration of the cancer, permit us to consider it a screening technique of primary importance. PMID- 7889074 TI - [Echography problems in acute scrotum: torsion of the hydatid of Morgagni]. AB - The A.A. discuss about a clinical case of acute scrotum in which the echographical aspects aren't been exhaustived for the etiology. Surgical exploration showed Morgagni's hydatid torsion while the echography doubted between acute phlogosis and neoplasia. PMID- 7889076 TI - [Diltiazem helps perfusion of the kidney after transplantation: intraoperative assessment using echo-color Doppler]. AB - Diltiazem is a dihydropyridinic calcium-antagonist which acts an arterial muscle, producing an increase in vascular capacity. We administered it intraoperatively in 2 patients subjected to kidney transplantation, to asses the maximal vascular reserve of the transplanted organ. After 2' and 10' from administration of Diltiazem, Color Doppler Ultrasound showed a 30% increase in mean flow in the renal artery and 13% reduction in the intraparenchymal resistance rates with respect to the basal parameters. Systemic arterious pressure remained unchanged. This result was associated with an improvement in the perfusion of the transplanted organ. PMID- 7889077 TI - [Transrectal echography of the prostate in the long-term follow-up of prostatic carcinoma in advanced stage]. AB - In the last eight years, 60 patients with carcinoma of the prostate in an advanced stage underwent transrectal ultrasound examinations of the prostate both before and after treatment with LHRH analogues, alone or associated with antiandrogens. Mean follow-up was 30 months (9-96 months) and mean survival 33 months (9-81). In all patients, the volume and echogeneicity of the prostate were assessed before treatment and once every three months thereafter. A significant reduction in volume was observed in 91% of the cases (54/60), while a variation in the echogeneicity was noted in 80% of the patients (48/60); these data do not seem to have been affected by the type of treatment administered. The greatest reduction in volume occurred during the first three months, after which a virtually constant volume was observed. Metastatic progression occurred in 29 of the 60 patients assessed, whereas no increase in prostate volume was demonstrated by ultrasound in 18 of these patients. These data, reported by other authors, too, may indicate that transrectal ultrasound examinations alone cannot constitute a complete follow-up in prostatic carcinoma: they can only show local progression and should therefore be associated with other diagnostic methods, in particular the specific prostate antigen. PMID- 7889078 TI - [Echo-color Doppler in renal transplantation: the clinician's needs]. AB - Kidney transplantation can lead to a number of complications of a urological and/or vascular nature. Early diagnosis of these complications may determine the survival of the organ. While diagnosis of urological-type complications can be made by means of non-invasive techniques like ultrasound investigation, vascular type complications often require invasive techniques using contrast medium, such as angiography. Recently, the possibility of using color doppler ultrasound, both intraoperatively and for follow-up, has been suggested, as a means not only of assessing anastomosis and renal perfusion but also of diagnosing any complications of a vascular nature. In the last two years, 51 kidney transplants have been performed at our centre; all patients underwent color doppler ultrasound. We report our experience paying particular attention to vascular complications. PMID- 7889079 TI - [Bilateral varicocele: diagnostic implications]. AB - If a varicocele is appreciated on the clinical examination, its presence may then be confirmed by Doppler examination. A pencil-probe Doppler stethoscope is utilized with ultrasonic conduction gel. The patient is examined in the upright position, and conducting medium is applied to the upper aspect of the scrotum. It is important that there is complete acoustic silence prior to having the patient perform the Valsalva maneuver. However, if a clinical varicocele is found on either the left or right side, the opposite side is evaluated for the presence of a "subclinical" varicocele by Doppler examination. When a "subclinical" varicocele is associated with a controlateral clinical varicocele, it is treated at the same time as the coexistent clinical varicocele. Venography is employed for the diagnosis of varicoceles only for patients in whom physical examination and Doppler studies are equivocal but highly suggestive of the presence of a varicocele. In that situation, rather than subjecting the patient to an unnecessary surgical procedure, venography may be employed to confirm the varicocele. Nowadays another diagnostic procedure is successfully used, that consists in a color ultrasound of the scrotum associated with Doppler velocimetry of the spermatic cord. PMID- 7889080 TI - [Echographic diagnosis of ureterocele]. PMID- 7889081 TI - [Treatment of renal cysts]. AB - The Authors report their experience in treatment of renal cysts by PCN ultrasound puncture: An aspiration technique is described. A sclerosing substance (sterile Alcohol 95%) has been injected into the cysts to prevent relapse by a pigtail catheter. Immediate and late results are discussed. The data obtained confirm this practice as the best choice in the treatment of this pathology. PMID- 7889083 TI - Premature ovarian failure associated with autoantibodies to the zona pellucida. AB - Immune disturbances are noted in up to 35% of women with premature ovarian failure. Previous investigators have focused on the presence of antibodies directed against steroid secreting cells of the ovary and the presence of lymphocytic infiltration in ovarian biopsy specimens. The authors report two cases of premature ovarian failure associated with antibodies directed against the zona pellucida. One of these two patients conceived while on estrogen replacement therapy. PMID- 7889082 TI - Urethral stricture and semen quality. AB - OBJECTIVE: To study the relationship between urethral stricture and infertility, which has not been well studied in the past. PATIENTS AND METHODS: In this study in West Africa, the mean semen values from 90 fertile controls and 32 infertile controls were compared to 40 men with incomplete urethral strictures (IUS) and 56 men with complete urethral strictures after treatment. Testicular biopsies were performed on 30 patients. Sexually transmitted urethritis accounted for 79% of the strictures within this group of patients. Repair of the strictures restored ejaculate in 39 men, and 22 men had normospermia (20 million/mL); however, the remainder had either azoospermia or oligospermia. The biopsies revealed normal spermatogenesis in 5 men, which suggested ductal obstruction, but 14 patients had destruction of seminiferous tubules suggesting end organ failure. Eleven other men had hypospermatogenesis, maturation arrest, or premature sloughing of cells, which may be amenable to treatment. CONCLUSIONS: These data suggest that early medical treatment and repair of urethral stricture may improve fertility for men with urethral strictures, especially strictures following infectious urethritis. Testicular biopsies may aid in the diagnosis of persistent infertility among these men, and should be considered as part of the work-up. PMID- 7889084 TI - The clinical significance of slightly elevated serum human chorionic gonadotropin levels. AB - The use of highly sensitive procedures for detecting human chorionic gonadotropin (hCG) has brought about an increasing occurrence of test results that are difficult to interpret. Furthermore, different results on the same serum sample can be obtained by different methods of measurement and, in extreme cases, serum hCG may be positive by one method and negative by the other. These observations are important, since patients may be hospitalized and receive unnecessary treatment as a result of confusing laboratory data. The clinical significance of slightly elevated serum hCG level is reviewed. PMID- 7889085 TI - Pregnant women's serum provides a novel support for human sperm hyperactivated motility. AB - OBJECTIVE: Medium composition and assay parameters for assessing human sperm hyperactivated motility (HA) were investigated during a time-course study. METHODS: The incidence of HA was studied, in vitro, in sperm samples incubated in eight different media compositions. HA was assessed using the 7.1 version of the Hamilton Thorn Motion Analyzer (HTM). RESULTS: The HA expressed at four hours with human tubal fluid (HTF) was 21.5 +/- 1.1% (mean +/- SEM), and that in Ham's F10 medium was 20.1 +/- 1.4% when the media were supplemented with pregnant women's serum (PWS), a novel support for HA. When fetal cord serum (FCS) was used instead of PWS, the HA exhibited was 16.8 +/- 2.3% and 13.5 +/- 2.35% in HTF and Ham's F10, respectively. Addition of human serum albumin (HSA) to HTF or Ham's F10 media supported HA peak at the four-hour time point (HTF, 19.5 +/- 5.0%; Ham's F10, 10.6 +/- 3.2%). On the other hand, the peak HA expressed in synthetic tubal fluid (STF) supplemented with PWS was 6.0 +/- 0.7% at the two-hour time point. Intra-Menezo B2 medium (IMB2) supported HA at the two- and four-hour time points, but not at six hours. HA appeared much less when Biggers-Whitten Whittingham (BWW) medium was used. CONCLUSION: PWS (10%) followed by FCS (7.5%) addition to media, especially HTF and Ham's F10, appears to enhance HA expression. PMID- 7889086 TI - Microscopic salpingitis is not an etiologic factor of tubal pregnancy with intrauterine devices. AB - OBJECTIVE: This prospective study was undertaken to test the hypothesis that microscopic chronic salpingitis is an etiologic factor in ectopic (tubal) pregnancy with an intrauterine device (IUD). PATIENTS AND METHODS: Fifty consecutive patients at a university hospital operated for tubal pregnancy fulfilled strict histological diagnostic criteria for tubal pregnancy. There were no statistically significant differences in prevalence of microscopic findings of chronic inflammation in patients who never used an IUD, had a history of IUD use, or had an IUD in situ at the time of laparotomy. Salpingitis isthmica nodosa was found in four patients (30.8%) without past or present history of IUD use as compared to two patients (5.4%) with past or present history of IUD (P < .05). CONCLUSION: The use of an IUD does not appear to cause tubal pregnancy by the mechanism of tubal inflammation or presence of salpingitis isthmica nodosa. Therefore, other mechanisms by which an IUD might cause ectopic pregnancy should be considered. PMID- 7889087 TI - Reversible effects of sodium fluoride ingestion on spermatozoa of the rat. AB - The effects of ingestion of sodium fluoride (NaF), 10 mg/kg body weight for 50 days, on the structure and metabolism of sperm of albino rats (Rattus norvegicus), were investigated. In different groups of rats, the reversible effects upon withdrawal of NaF treatment and by administering some therapeutic agents, viz., ascorbic acid and calcium alone and in combination with NaF (50 and 70 days), on sperm structure and metabolism were also studied. The results revealed that the sperm acrosomal hyaluronidase and acrosin were reduced after 50 days of NaF treatment. Sperm stained with acidic alcoholic silver nitrate revealed acrosomal damage and deflagellation, which might be causative factors for the reduced activity of the enzymes. These alterations also resulted in a decline in sperm motility. The cauda epididymal sperm count was decreased, perhaps because of spermatogenic arrest. Thus, the low sperm motility and count ultimately contributed toward reduction in fertility by NaF treatment. However, withdrawal of NaF treatment for 70 days produced incomplete recovery, while administration of ascorbic acid and calcium, individually and in combination, brought about significant recovery of fluoride-induced effects. Thus, the effects of fluoride on sperm structure and metabolism of rats are transient and reversible. PMID- 7889089 TI - Strategic information issues: move quickly--and play it smart. PMID- 7889090 TI - Inflation outpaces benefit cost hikes. PMID- 7889088 TI - Spermatozoal abnormalities and male infertility in the rat following sulfasalazine treatment. AB - OBJECTIVE: To determine the (reversible) antifertility effect in the male rat of sulfasalazine, a common therapy for inflammatory bowel disease. METHODS: Sulfasalazine (120, 250 and 500 mg/kg) was administered for 60 days by oral gavage to sexually mature male rats. RESULTS: Both motility of sperm and fertility of animals was significantly altered at the highest dose (500 mg/kg). Morphological abnormalities included alteration in the normal profile of the spermatozoa and presence of lesions on the sperm head. CONCLUSIONS: Results suggest that sulfasalazine brings about its antifertility effects by altering sperm motility and number of spermatozoa in addition to increased surface abnormalities, which render the spermatozoa infertile. PMID- 7889091 TI - Strategic planning ... survey of 156 physician-hospital organizations. PMID- 7889093 TI - MHA rates most popular health programs in their state. PMID- 7889092 TI - Employed doctors' raises outpace pay for other staff. PMID- 7889094 TI - Street wise. Wall Street: where health care is suddenly hot. AB - With market-driven reform sweeping the health care field, Wall Street is betting on those hospital systems that are revamping themselves for cost-effectiveness and demonstrated value to payers. Analysts are encouraged by such markers as overcapacity shrinkage, full-asset mergers and hospital swaps. And they're positively bullish on Columbia/HCA. PMID- 7889095 TI - 1986 Foster G. McGaw prize winner. Lutheran Medical Center, Brooklyn, New York. PMID- 7889096 TI - Playing by the rules: MD groups and antitrust. AB - Physicians forming networks often find their efforts blocked by state and federal antitrust laws. Yet despite the chilling example of the Marshfield Clinic ruling, physician-driven networks are moving ahead and creating new entities--from Idaho to New Jersey. PMID- 7889097 TI - The long view on long-term care. PMID- 7889099 TI - Integrated care. Watch for flying phrases. PMID- 7889098 TI - The computer revolution snags some physicians in & out of the office: it's time to recognize the new era of the techno docs. PMID- 7889100 TI - Medical mistakes. The price of doing it over. PMID- 7889101 TI - Maneuvers. More than paper shuffling. PMID- 7889102 TI - Diversions. Dr. Shutterbug. AB - When not working as emergency department director at Milford (DE) Memorial Hospital, Elsburgh Clarke, M.D., can be found snapping photos of everything from professional sports to doctors saving lives. PMID- 7889103 TI - Cookbook insurance. Restaurant staff serves up their own health care benefits. PMID- 7889104 TI - PHO capitation: 10-step model. PMID- 7889105 TI - Road less traveled. PMID- 7889107 TI - 19-Noraldosterone, a new mineralocorticoid. PMID- 7889106 TI - Localization of steroidogenic enzymes in adrenal cortex and its disorders. AB - Immunolocalization and in situ hybridization analysis of steroidogenic enzymes demonstrated the localization of steroidogenesis in the adrenal cortex and its disorders. The findings obtained provided new insights into adrenocortical hormonal metabolism, especially through establishing endocrine-pathological correlation. PMID- 7889108 TI - Recent advances in endothelin research on cardiovascular and endocrine systems. AB - Recent advances in ET research on the cardiovascular and endocrine systems were reviewed. Considering the potent vasculotropic actions, strategically advantageous localization, and recent findings with the specific receptor antagonist, ET is potentially involved in the regulation of hemodynamic homeostasis and in the pathogenesis of essential and secondary hypertension. The mitogenic action on the vascular smooth muscle cells suggests its more chronic effect on the vascular structure. In addition to the hypertensinogenic aspects, the role of ET in maintaining blood pressure in a hypotensive condition should not be overlooked. The development of specific antagonists which block the action of locally operating ET in vivo will be a powerful tool in elucidating the pathophysiological significance of ET and will provide a new therapeutic approach for hypertension. The roles of ET in the endocrine system are also fascinating. Accumulating evidence supports the notion that ET modulates the secretion of pituitary and adrenal hormones. The mode of action is likely to be paracrine/autocrine rather than endocrine, although a possible role of circulating ET cannot be ruled out. The pathophysiological role of ET in the endocrine tissues remains to be clarified. The diversity of the action of ET on the blood pressure and endocrine functions provides further evidence of the complexity of the homeostatic mechanisms, leaving us an intriguing subject for future study. PMID- 7889109 TI - Human chorionic gonadotropin secretion and protein phosphorylation in chorionic tissue. AB - The signal transduction system acts either monodirectionally (synergistically) or bidirectionally (antagonistically) in different tissues. We activated the signal transduction system in BeWo human choriocarcinoma cells and studied the effects on human chorionic gonadotropin (hCG) secretion, cell proliferation, and DNA synthesis. Protein phosphorylation in the cytosolic fraction was also studied by two-dimensional polyacrylamide gel electrophoresis. When phorbol 12-myristate 13 acetate (PMA) was added to cultures, hCG secretion was increased dose dependently, but cell proliferation and 3H-thymidine uptake were not affected. When only cholera toxin was added, hCG secretion was also stimulated dose dependently, but when both PMA and cholera toxin were added there was a synergistic potentiation of hCG production. In contrast, Ca ionophore A23187 had almost no effect on hCG secretion. Two-dimensional gel electrophoresis and autoradiography showed that phosphorylation of a 33 kd acidic protein was produced by cholera toxin, while phosphorylation of a 45 kd acidic protein and dephosphorylation of a 14 kd acidic protein were caused by the phorbol ester. These proteins may be specific substrates of protein kinase A and protein kinase C, respectively, in BeWo cells. PMID- 7889111 TI - Changes in endogenous growth hormone secretion and onset of puberty in transgenic rats expressing human growth hormone gene. AB - A chimeric gene comprising murine whey acidic protein (mWAP) and human growth hormone (hGH) was used to produce transgenic rats that express hGH and secrete it into the blood. Two lines of transgenic rats carrying the mWAP/hGH construct were established: Line 1 was characterized by relatively high levels of serum hGH, and Line 2 had relatively low levels. The secretory profiles of rat GH (rGH) as well as hGH, the transgene product, were obtained in transgenic males and females of Line 2; both hGH and rGH serum levels were flattened with no episodic fluctuations, and the overall mean concentration of rGH was significantly lower than in normal littermates. Although the animals of Line 1 showed an accelerated increase in growth rate, those of Line 2 did not. Nevertheless, the onset of puberty in females, as assessed by vaginal opening and occurrence of first ovulation, advanced by 7-8 days in both Lines of animals. Accordingly, the body weight at puberty of Line 2 transgenic females was much lower than that of normal littermates, indicating that continuous hGH expression could induce precocious puberty without enhancing the growth rate. PMID- 7889110 TI - Relationship between thyroid functions and urinary growth hormone secretion in patients with hyper- and hypothyroidism. AB - Thyroid hormone plays an important role in growth hormone (GH) synthesis and secretion. To study the relationship between thyroid function and urinary GH secretion in the hyperthyroid and hypothyroid states, we measured thyroid hormones, simultaneously with serum and urinary GH levels, in 54 patients with thyroid diseases. GH-releasing hormone (GRH) test was performed in 18 patients in order to evaluate serum and urinary GH responses to GRH in hyper- and hypothyroid states. Serum thyroid hormone levels were strongly correlated with the urinary GH levels in the patients, and the correlation was greater than that between serum thyroid hormone and serum GH levels. Urinary GH levels were significantly higher in the hyperthyroid patients than in the euthyroid and hypothyroid patients, although serum GH levels were not significantly different among these three groups. Serum GH response to GRH was significantly decreased in hyperthyroid patients as compared to euthyroid patients. However, urinary GH levels after GRH administration were not decreased in the hyperthyroid patients. These results suggest that hyperthyroid states increase GH in urine and may accelerate the urinary clearance of GH. PMID- 7889112 TI - Hypopituitarism with invisible pituitary stalk: two case reports of males with micropenis suggesting fetal onset of hypopituitarism. AB - The presence of hypopituitarism and invisible pituitary stalk on a magnetic resonance image (MRI) is commonly attributed to birth trauma. Two patients with severe hypopituitarism and invisible pituitary stalk are presented. One was born by breech delivery, the other by Cesarean section. The presence of a micropenis since early infancy in these two patients suggested that their hypopituitarism might have begun during early fetal life thus effecting penile growth during the second and third triministers of gestation. These findings raise the possibility that the association of hypopituitarism and invisible pituitary stalk may have multiple etiologies including hormonal abnormalities during early fetal life. PMID- 7889113 TI - Pituitary function in patients with Rathke's cleft cyst: significance of surgical management. AB - The pituitary function of patients with Rathke's cleft cyst before and after surgery was investigated to clarify the significance of surgery and operative indications. The authors have treated 19 patients with Rathke's cleft cyst. There were panhypopituitarism in 2 patients (11%), amenorrhea and/or galactorrhea in 3 (16%), diabetes insipidus in 4 (21%), and visual disturbance in 9 (47%). All the patients underwent systematic endocrinological examination and were found to have various degrees of pituitary dysfunction. Panhypopituitarism was endocrinologically confirmed in 2 patients. Hyperprolactinemia was observed in 4. These patients underwent aspiration of the cyst contents and biopsy of the cyst wall. Postoperative follow-up endocrinologic evaluation performed more than 3 months after surgery showed improvement in pituitary function in 9 out of 13 patients (69%). Amenorrhea and/or galactorrhea recovered or improved in 100% of patients and visual disturbance improved in 89%. However, diabetes insipidus and panhypopituitarism did not improve postoperatively, in any patient. The results of the present study indicate that the incidence of pituitary dysfunction in patients with Rathke's cleft cyst is higher than suspected and in most cases surgical intervention improves pituitary function and the clinical status of the patient. Therefore, surgical treatment is recommended even when the patient has only mild symptoms or signs, including pituitary dysfunction, to prevent irreversible panhypopituitarism. PMID- 7889114 TI - Change in serum concentration of insulin-like growth factor II (IGF-II) in patients with thyroid disease. AB - We investigated the serum concentration of IGF-II in patients with thyroid diseases (25 with untreated Graves' patients, 30 with hypothyroidism, 23 with thyroid adenoma) and in 72 healthy adults as normal controls, by a sensitive radioimmunoassay of serum IGF-II. Thyroid hormones are known to increase IGF-I production in the liver through the enhancement of GH secretion. In case of IGF II, however, knowledge has been rather limited. The mean +/- SD concentration in healthy subjects was 556 +/- 94 micrograms/L with neither sex nor age dependence. In untreated Graves' patients, serum IGF-II levels (675 +/- 129 micrograms/L) were significantly (P < 0.01) higher than in normal controls, and significantly lower in patients with hypothyroidism (460 +/- 106 micrograms/L; P < 0.01). Thyroid hormones revealed positive correlation with the IGF-II concentration. PMID- 7889115 TI - The effect of interleukin-2 on the release of gonadotropin and prolactin in vivo and in vitro. AB - To evaluate a possible physiological role of Interleukin-2 (IL-2) in the control of Luteinizing hormone (LH), Follicle stimulating hormone (FSH) and Prolactin (PRL) release, conscious, ovariectomized (OVX) rats were given injections of IL-2 into the third ventricle. The third ventricular injection of IL-2 induced a significant decrease in plasma LH levels when compared to values in control animals (P < 0.05). Plasma LH concentrations were significantly decreased within 5 min after the injection of IL-2 and remained decreased for 1 h. In contrast, injections of IL-2 had no effect on plasma FSH or PRL levels. To evaluate a possible direct action of IL-2 on LH, FSH and PRL release from the anterior pituitary gland, the cytokine was incubated with dispersed anterior pituitary cells for 4 h. IL-2 in the dose range between 10(-1) and 10(-3) unit stimulated the release of LH and FSH into the culture medium (P < 0.05, P < 0.025 vs. control, respectively). The release of PRL from incubated anterior pituitary cells was not affected at any dose of IL-2 tested. These results indicate that IL 2 possibly plays an inhibitory role in the control of gonadotropin secretion, via hypothalamic action, although it acts directly to stimulate the release of the gonadotropins at the level of the anterior pituitary gland. PMID- 7889116 TI - Corticotropin-releasing factor-binding protein concentrations in plasma of patients with hypothalamic-pituitary-adrenal disorders. AB - Immunoreactive corticotropin-releasing factor-binding protein (CRF-BP) concentrations in human plasma were determined by means of radioimmunoassay for human CRF-BP. CRF-BP antiserum to the C-terminal fragment of human CRF-BP (298 322) was produced, and CRF-BP (298-322) was used as the tracer and the standard. Large amounts of human CRF did not affect measurement of plasma CRF-BP with this radioimmunoassay. The basal plasma CRF-BP concentration in normal subjects was 4.19 +/- 0.57 nmol/L (mean +/- SD). The CRF-BP concentration was low in patients with Cushing's syndrome, except those with preclinical Cushing's syndrome, and high in patients with Addison's disease, hypopituitarism and isolated ACTH deficiency. After surgery, the plasma CRF-BP concentration in patients with Cushing's syndrome rose, peaked, and then decreased to the control level. In patients with Addison's disease, the high plasma CRF-BP concentration decreased to the control level after hydrocortisone replacement, the same as plasma ACTH concentration. These findings suggest that the immunoreactive CRF-BP concentration in human plasma was decreased by glucocorticoids, at least under chronic conditions. PMID- 7889117 TI - Microinjection of LHRH and its antagonistic analog into the medial preoptic area does not affect pulsatile secretion of LH in ovariectomized rats. AB - To gain a better understanding of the existence of an ultra-short feedback mechanism controlling LHRH secretion in the medial preoptic area (MPO), we examined the effects of microinjections of LHRH or the LHRH antagonist [D-pGlu1, D-Phe2, D-Try3,6] into the MPO on pulsatile secretion of LH in ovariectomized rats and on the surge of LH secretion in proestrous rats. Neither the injection of 10 ng LHRH nor 100 ng its antagonist into the MPO had any effect on pulse frequency or the mean LH concentration in ovariectomized rats. The injection of 100 ng LHRH antagonist or 10 ng LHRH delayed or advanced, respectively, the LH surge in proestrous rats. Taking these results together with our previous report, the present study indicates that 1) endogenous LHRH in the MPO is involved in the ultra-short feedback regulation of LHRH release and 2) the ultra-short positive feedback mechanism in the MPO acts at the time of the proestrous LH surge but not under a hormonal milieu as in ovariectomized rats. PMID- 7889118 TI - Exacerbation of thyroid autoimmunity by interferon alpha treatment in patients with chronic viral hepatitis: our studies and review of the literature. AB - In the present studies, the long term effects of IFN alpha on thyroid function and thyroid autoantibodies were evaluated in 42 patients with chronic viral hepatitis type C treated with IFN alpha for at least 4 months. Before IFN treatment, 41 patients tested were all euthyroid. Five (12%) out of 24 patients tested had positive tests for thyroid autoantibodies. MCHA/TPOAb was detected in all 5 and TGHA/TGAb in 3 out of these 5 patients. Six to 10 x 10(6) units (U) of recombinant or natural IFN alpha were given intramuscularly daily for the first 2 to 4 weeks, followed by 3 to 10 x 10(6) U thrice weekly for the subsequent 14 to 22 weeks. Thyroid dysfunction and/or rises in titers of thyroid autoantibodies were observed in 6 patients during IFN alpha treatment; clinically overt thyroid dysfunctions, destructive thyroiditis and thyrotoxicosis of unidentified etiology, developed in 2 patients 4 to 5 months after start of IFN treatment, subclinical hypothyroidism with a slight increase in serum TSH concentrations but no serum thyroid hormone alternations was observed in 2 patients, and increases in titers of thyroid autoantibodies without thyroid dysfunction were found in 2 patients. Thus, IFN alpha exacerbated thyroid autoimmunity exclusively in all patients with positive tests for thyroid autoantibodies prior to treatment, but did not induce thyroid autoimmunity in thyroid autoantibody-negative patients. These data suggest that the prolonged IFN alpha therapy can lead to exacerbation of thyroid autoimmunity in susceptible (thyroid autoantibody-positive) patients. PMID- 7889119 TI - The use of antiandrogen flutamide in the treatment of hirsutism. AB - In this study the efficacy of flutamide, an antiandrogen which does not have a steroid structure, or progestational and estrogenic activities, on hirsutism and hormone levels in polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) was investigated. Ten patients with PCOS and nine patients with IH between 19 and 36 years of age were selected for the study. They were given a 500 mg daily dose of flutamide and were followed up for clinical and hormonal effects at the second, sixth, eighth and twelfth months of the treatment. The severity of hirsutism was assessed according to the Ferriman-Gallwey's score. There was a slight decrease to below the pre-treatment level in serum LH at the end of the eighth month (P < 0.05) and there was also a persistent decrease in progesterone (P) after the second month of the treatment (P < 0.05). No other significant change was observed in ovarian or adrenal androgens. Clinical examinations revealed that after six months of the therapy the dose of flutamide had caused a significant alleviation of hirsutism and this continued during the following months. PMID- 7889120 TI - Increase in Pit-1 mRNA is not required for the estrogen-induced expression of prolactin gene and lactotroph proliferation. AB - Estrogen has been shown to stimulate lactotroph proliferation and expression of the prolactin (PRL) gene. Recently it has been established that Pit-1, a pituitary-specific transcription factor, is required for lactotroph proliferation. Furthermore, in vitro studies showed that an increase in the PRL promoter activity caused by estrogen was dependent of the amount of cotransfected Pit-1-expressing plasmid. These findings led us to examine whether the induction of Pit-1 mRNA is required for the estrogen-increased PRL gene expression in the rat anterior pituitary in vivo. Short term estrogen treatment was achieved by means of a single intramuscular injection of estradiol dipropionate. DNA synthesis, the levels of PRL and Pit-1 messenger RNAs in the anterior pituitary were determined. Estradiol dipropionate resulted in a significant increase in DNA synthesis 24 h after administration and in PRL mRNA after 48 h. In contrast, the Pit-1 mRNA level was not altered. Since Pit-1 is expressed not only in lactotroph but also in somatotroph and thyrotroph, and the lactotroph cell population has been reported to be less than 10% in the pituitary, the change in the Pit-1 mRNA level in lactotrophs was not seen following only short term estrogen treatment. An increase in the lactotroph cell population was therefore achieved by chronic estrogen treatment (subcutaneous implantation of a silastic tube containing 17 beta-estradiol powder for 30 days). This treatment resulted in the marked proliferation of lactotrophs and a 3-fold increase in PRL mRNA. However, no alteration in Pit-1 mRNA was observed. These results suggest that the increase in Pit-1 mRNA is not required for the estrogen-induced lactotroph proliferation or PRL gene expression. PMID- 7889121 TI - Effect of growth hormone (GH)-releasing peptide (GHRP) on the release of GH from cultured anterior pituitary cells in cattle. AB - The effect of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP) on growth hormone (GH) release from cultured bovine anterior pituitary (AP) cells was studied in vitro with the interactive effects of GH-releasing factor (GRF: hpGRF (1-29)-NH2) and somatostatin (SRIF). The AP cells (5 x 10(4) cells per well) were incubated with media, and the media were changed 3 days after plating. After 3.5 days in culture, cells were incubated for 2 h with the peptides. GHRP stimulated GH release from cultured cells in a dose-related manner. At doses from 10(-11) to 10(-7) M GHRP, the amount of GH released was significantly greater than the controls (P < 0.05 to P < 0.001). The amounts of GH released at lower doses of GHRP (10(-14) to 10(-12) M) were not significantly different from the controls. GH concentrations after treatment with 10(-11) and 10(-7) M GHRP were 3.98 +/- 0.27 and 4.81 +/- 0.16 ng/ml, respectively. In experiments performed similarly, the 10(-7) M GHRH, GHRP, and combined treatment with GHRP plus GHRH increased GH 126, 57, and 139%, respectively (P < 0.001). The GH releasing effects of either GHRH alone or GHRP plus GHRH were significantly more potent than that of GHRP alone (P < 0.001). The additive effect was not significant when compared with GHRH alone. GH release induced by either GHRH or GHRP was significantly inhibited by SRIF (P < 0.01) compared with the untreated control. The inhibitory effect of SRIF in combined treatment with GHRP plus GHRH was significantly less than that of SRIF with GHRH or with GHRP (P < 0.01). The present study suggests that GH releasing peptide (GHRP) induced GH release in cattle via a direct action on anterior pituitary cells in vitro. PMID- 7889123 TI - Model of local connectivity patterns in CA3 and CA1 areas of the hippocampus. AB - In this study we describe a model of connectivity linking the different neurons in the CA3 and CA1 areas of the young male rat hippocampus. The anatomical and electrophysiological values of the parameters used in the model were selected from the available literature. Each type of synapse was characterized by its spatial location on the dendritic tree, its weight, its probability of activation, and the ionotropic receptors involved. We have shown that the degree of convergence and divergence of inputs is highly dependent upon the type of neuron and its spatial location. The different gradients of connectivity we describe support the lamellar hypothesis from a functional point of view, even if the anatomical patterns seem diffuse. The analysis of the proportion of common afferents to a class of neurons further confirmed this point. It is suggested that the circuitry creates local coherence in terms of processing of information by establishing restricted areas where information is preferentially treated. The functional consequences and limitations of these findings are also discussed. This model is the first step in the development of a network model of the hippocampus with realistic architecture. PMID- 7889122 TI - Cholera toxin can ADP-ribosylate Gs as well as Gi in ACTH-unresponsive human adrenocortical cancer. AB - It is well known that cholera toxin (CT) stimulates ADP-ribosylation of Gs and also pertussis toxin (PT) does Gi. Each GTP-binding protein has its own action in the regulation of adenylate cyclase. A human non-functioning adrenocortical cancer tissue showed an unresponsiveness in adenylate cyclase to ACTH although ACTH and CT activated adenylate cyclase in a non-functioning adrenal adenoma tissue. CT ADP-ribosylated 43 kDa protein of the plasma membrane of the cancer tissue while CT and PT could ADP-ribosylate 43 kDa and 38 kDa protein in the adenoma tissue, respectively. Immunoblotting analysis of the cancer tissue demonstrated that 40 kDa protein was detected by anti-Gs antibody as well as by anti-Gi antibody. The present experiments demonstrated that CT could ADP ribosylate Gs which has stimulatory action on adenylate cyclase and also Gi which inhibits adenylate cyclase. Thus it is suggested that CT can activate the ADP ribosylation of Gs and also Gi in a human adrenocortical cancer tissue, partly resulting in abnormal regulation of adenylate cyclase which may be crossly related to ACTH-unresponsiveness. PMID- 7889124 TI - Localization of mRNAs encoding two forms of glutamic acid decarboxylase in the rat hippocampal formation. AB - The mRNAs for two forms of glutamic acid decarboxylase (GAD65 and GAD67) were localized in the rat hippocampal formation by nonradioactive in situ hybridization methods with digoxigenin-labeled cRNA probes. Some neurons in all layers of the hippocampus and dentate gyrus were readily labeled for each GAD mRNA, and the patterns of labeling for GAD65 and GAD67 mRNAs were very similar. All major groups of previously described GAD- and GABA-containing neurons appeared to be labeled for each GAD mRNA. Such findings suggest that most GABA neurons in the hippocampal formation contain both GAD mRNAs. When the labeling of neurons in the hippocampal formation and cerebral cortex was compared in the same sections, the intensity of neuronal labeling for GAD67 mRNA was generally similar in the two regions. However, the intensity of labeling for GAD65 mRNA was generally stronger for many neurons in the hippocampal formation than for most neurons in the cerebral cortex. Neurons in the hilus of the dentate gyrus were particularly well labeled for GAD65. The nonradioactive labeling for the GAD mRNAs was confined to the cytoplasm of neuronal cell bodies, and this allowed a clear visualization of the relative number and location of labeled neurons. Several distinct patterns of GAD mRNA-containing neurons were observed among different regions of the hippocampal formation. In the hilus of the dentate gyrus, GAD mRNA-containing neurons were numerous in the regions deep to the granule cell layer as well as in more central parts of the hilus. Within CA3, the densities (quantities) of labeled neurons varied among the regions. In the inner or hilar segment of CA3, the density of labeled neurons was often lower than that in the outer part of CA3 where numerous labeled neurons were distributed throughout all layers. In CA1, GAD mRNA-labeled neurons were distributed in a relatively laminar pattern with the highest density in stratum pyramidale and moderate densities in stratum oriens and at the interface between strata radiatum and lacunosum-moleculare. Lower densities were found within the latter two layers. The prominent localization of the two GAD mRNAs in the hippocampal formation suggests that a dual system for GABA synthesis is necessary for normal GABAergic function in this brain region. Most putative GABA neurons contain relatively high levels of GAD67 mRNA as might be expected if this GAD form is responsible for the synthesis of GABA for metabolic and baseline synaptic function.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 7889125 TI - Dendritic Ca2+ accumulations and metabotropic glutamate receptor activation associated with an N-methyl-D-aspartate receptor-independent long-term potentiation in hippocampal CA1 neurons. AB - Bathing hippocampal slices in the potassium channel blocker tetraethylammonium (TEA), while stimulating the Schaffer collaterals at a low frequency, induces Ca(2+)-dependent, N-methyl-D-aspartate (NMDA) receptor-independent long-term potentiation of synaptic transmission (LTPk) in CA1 neurons. We have combined ratio imaging of fura-2 and mag-fura-5 in hippocampal CA1 neurons with intracellular and field recordings to evaluate postsynaptic Ca2+ changes that occur in the induction of LTPk. Test stimuli were applied at 0.05 Hz to stratum radiatum in the presence of the NMDA receptor antagonists D,L-2-amino-5 phosphonovaleric acid (100 microM) or MK-801 (10 microM). During TEA exposure (15 25 mM; 10 min), cells fired prolonged action potentials both spontaneously and in response to test stimuli resulting in transient, micromolar Ca2+ accumulations in both somata and dendrites. The initial EPSP slope, measured 60 min after TEA wash out, was potentiated to approximately 200% of control. The Ca2+ channel blocker nimodipine (10 microM) greatly reduced Ca2+ transients in both magnitude and duration and prevented LTPk induction. Pretreatment of slices with compounds that block metabotropic glutamate receptor (mGluR)-stimulated phosphoinositide hydrolysis, L-2-amino-3-phosphonopropionic acid (L-AP3, 50-200 microM) or L aspartate-beta-hydroxamate (50-100 microM), as well as protein kinase C (PKC) inhibitors (sphingosine, 20 microM; RO-31-8220, 0.2 microM; or calphostin C, 2 microM) also blocked LTPk. Ca2+ transients were unaffected by L-AP3 or RO-31 8220. These findings suggest that Ca2+ influx through voltage-gated channels and co-activation of PKC by mGluRs are both necessary for induction of LTPk. Activation of mGluRs must also occur in NMDA receptor-dependent induction paradigms, but is possibly of lesser importance owing to the much greater gating of Ca2+ directly into the dendritic spines. PMID- 7889127 TI - Development of inhibitory and excitatory synaptic transmission in the rat dentate gyrus. AB - We studied the ontogeny of inhibitory and excitatory processes in the rat dentate gyrus by examining paired-pulse plasticity in the hippocampal slice preparation. The mature dentate gyrus produces characteristic paired-pulse responses across a wide range of interpulse intervals (IPI). Paired-pulse effects on population excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude were analyzed at postnatal day 6 (PN6), PN7/8, PN9/10, PN15/16, and PN > 60. The synaptic paired-pulse profile (10-5,000 ms IPI) matured by PN7/8. The triphasic pattern of short-latency depression, a relative facilitation at intermediate intervals, and long-latency depression was present at all ages tested. Paired-pulse effects on granule cell discharge indicated the presence of weak short-latency (20 ms IPI) inhibition at PN6, the earliest day that a population spike could be evoked. By PN7/8, short-latency inhibition was statistically equivalent to the mature dentate gyrus. Long-latency (500-2,000 ms IPI) PS inhibition was present, and equal to the mature dentate gyrus by PN6. The most consistent difference between the mature and developing dentate gyrus occurred at intermediate IPIs (40-120 ms) where spike facilitation was significantly depressed in the development groups. The studies indicate that short-term plasticity matures rapidly in the dentate gyrus and suggest that the inhibitory circuitry can function at a surprisingly early age. PMID- 7889126 TI - Genetic and activity-dependent regulation of zif268 expression: association with spatial learning. AB - We have reported that C57BL/6 and DBA/2 mice differ in spatial learning performance and associated hippocampal protein kinase C (PKC) activity (Upchurch and Wehner, 1989, Behav Neurosci 103:1251-1258; Wehner et al., 1990, Brain Res 523:181-187) and that physical activity enhances spatial learning with related alterations in protein kinase C (PKC) (Fordyce and Wehner, 1993b, Brain Res 619:111-119). To assess whether physical activity induces alterations in gene expression that may underlie these changes in PKC and learning performance, we examined the effect of physical activity on expression of zif268, a transcription regulatory factor linked to stimulus-induced neuronal plasticity. C57 and DBA mice, 3 months of age, were subjected to acute (one bout) or chronic (8 weeks) physical activity. The mice were then tested on the Morris water maze task for 6 days with subsequent analysis of PKC activity and zif268 mRNA expression. Control DBA mice, which have poor hippocampal-specific learning performance compared to C57 mice (Wehner et al., 1990, Brain Res 523-181-187; Fordyce and Wehner, 1993b, Brain Res 619:111-119; Paylor et al., 1993, Psychobiology 27:11-26), displayed lower basal levels of zif268 mRNA (P < .05). As observed previously, chronic physical activity produced an enhancement in spatial learning performance accompanied by alterations in hippocampal PKC activity in both strains of mice (P < .05). In addition, the present investigation demonstrated that acute physical activity increased mRNA levels of zif268 in hippocampal regions CA1, CA3 and overlying cortex (P < .005) of both C57 and DBA mice. Chronic physical activity suppressed the basal expression of zif268 in C57 mice in CA1 and overlying cortex below control levels. These findings suggest that genetic and activity-dependent regulation of zif268 may influence learning performance. PMID- 7889128 TI - "Short-stops" in rats with fimbria-fornix lesions: evidence for change in the mobility gradient. AB - Rats with damage to the hippocampal formation and allied structures are hyperactive in many test situations but the cause of this hyperactivity is not known. Here the activity of control rats and rats with fimbria-fornix lesions is documented in tests of overnight activity. Details of activity are then characterized from video recordings of behavior in an open field. Rats with fimbria-fornix lesions make significantly more stops of shorter duration and thus more individual trips than control rats but they do not differ in the distance traveled on individual trips or in travel speed. It is suggested that the main difference between fimbria-fornix rats and control rats is that when fimbria fornix rats stop they remain "still" for shorter durations than do control rats. This finding is discussed in relation to a theory of locomotor/exploratory behavior, and in relation to its implications with respect to the performance of fimbria-fornix rats in studies of learning and memory. PMID- 7889129 TI - Alterations of inhibitory synaptic responses in the dentate gyrus of temporal lobe epileptic patients. AB - The number of orthodromically evoked population spikes was used to classify brain slice tissue from the dentate gyrus of temporal lobe epileptic patients as "more excitable" (multiple population spikes) or "less excitable" (a single population spike). During orthodromic stimulation, "more excitable" tissue exhibited less paired-pulse depression in comparison to "less excitable" tissue. During antidromic stimulation, both multiple population spikes and paired-pulse depression were observed in "more excitable" tissue. "Less excitable" tissue exhibited a single antidromic spike and often no antidromically evoked paired pulse depression. The strength of antidromic paired-pulse depression was correlated positively with the number of antidromic spikes and was correlated negatively with orthodromic paired-pulse depression. Although orthodromic and antidromic paired-pulse depression were correlated to the number of orthodromically evoked population spikes, this correlation was not as strong as that between orthodromic paired-pulse depression, antidromic paired-pulse depression, and number of antidromically evoked population spikes. The antidromic paired-pulse depression observed in tissue exhibiting antidromically evoked multiple population spikes was enhanced rather than blocked by bicuculline. In addition, the blockade of the antidromic paired-pulse depression by CNQX indicated that this inhibition is mediated by an AMPA-type glutamatergic synapse. We suggest that alterations in circuitry occur in the dentate gyrus of some temporal lobe epileptic patients and were manifested by both a loss of inhibitory input as well as an increase of inhibition, which was dependent on the pathway of stimulation. The results of pairing antidromic and orthodromic stimuli were consistent with these conclusions. PMID- 7889130 TI - Ultrastructural plasticity of the dentate gyrus granule cells following recurrent limbic seizures: I. Increase in somatic spines. AB - Various paradigms have been used to assess the capacity of the adult brain to undergo activity-dependent morphological plasticity. In this report we have employed recurrent limbic seizures as a means of studying the effects of this form of enhanced neuronal activity on cellular morphology and, in particular, on the incidence of somatic spines on the dentate gyrus granule cells. Seizure activity was induced by the placement of focal, unilateral electrolytic lesions in the dentate gyrus hilus of adult rats. At various intervals postlesion, rats with behaviorally verified seizures were sacrificed, and the hippocampi contralateral to the lesions were removed and prepared for electron microscopy. Quantitative analysis showed that as early as 5 hours postlesion there was a dramatic increase in the density and morphological complexity of spines on the perikarya of the granule cells in rats that received seizure-producing hilus lesions when compared to granule cells from control rats. Many of the somatic spines received asymmetric synapses. The increase in somatic spines was dependent on seizure activity and persisted for at least 1 month following a single recurrent seizure episode. CA1 pyramidal neurons, which exhibit changes in gene expression in response to hilus lesion-induced seizures but do not normally possess somatic spines, did not exhibit an activity-dependent elaboration of somatic spines. Thus, the seizure-induced elaboration of somatic spines represents an amplification of an existing feature of the granule cells and not an effect occurring throughout hippocampus. These data provide evidence for very rapid and long-lasting structural plasticity in response to brief episodes of seizure activity in the adult brain. PMID- 7889131 TI - Ultrastructural plasticity of the dentate gyrus granule cells following recurrent limbic seizures: II. Alterations in somatic synapses. AB - Hilus lesion-induced recurrent limbic seizures cause a dramatic increase in the numbers of somatic spines on dentate gyrus granule cells in the adult rat. Somatic spines are maximally increased 3 h after the initiation of seizures at which time many of these spines form synapses. The present quantitative electron microscopic study assessed the numbers and types of synapses present on the granule cell perikarya and somatic spines of control and experimental seizure rats with the goal of determining if newly elaborated somatic spines arise at the site of pre-existing synapses or are associated with new innervation. Experimental rats were sacrificed 5 h after hilar lesion placement (or 3 h after seizure onset). In both control and hilus-lesioned (HL) rats, 15-20% of the somatic spines could be seen to form synaptic contacts within a single plane of section; these synapses were almost exclusively of the asymmetric type. With the increased incidence of spines in experimental-seizure rats, there was a 6.25-fold greater number of spine synapses in HL versus control rats. There was, in addition, a 60% decrease in the number of asymmetric synapses occurring directly on the granule cell perikarya but no change in the total (spine plus somatic) number of asymmetric synapses. Although few asymmetric synapses were associated with spines in control tissue, 60-70% of asymmetric synapses were associated with spines in experimental-seizure tissue. In addition, in hilus lesion rats symmetric somatic synapses were increased by 20% on cells in deep stratum granulosum resulting in a dissolution of the superficial-to-deep innervation gradient present in the untreated rat. These findings support the conclusion that spines induced by seizure activity form at the site of pre-existing asymmetric synapses on the granule cells and demonstrate that brief seizure episodes can rapidly induce marked changes in innervation patterns in the adult brain. PMID- 7889132 TI - Lazaroid pretreatment preserves gas exchange in endotoxin-treated dogs. AB - PURPOSE: The lazaroids are a new class of potent free-radical scavengers. We tested whether U-74389G, a lazaroid, could attenuate some of the adverse cardiopulmonary effects of sepsis. METHODS: Dogs were randomized to receive either 10 mg/kg U-74389G (n = 10), or a saline control (n = 11). After baseline measurements of hemodynamics and gas exchange, they were then randomized to receive either 0.2 mg/kg endotoxin or a saline infusion. Measurements of hemodynamics and gas exchange were repeated. The study was concluded 70 minutes after endotoxin infusion and the lungs were then removed for histologic evaluation. RESULTS: In endotoxin-treated control animals, PO2 decreased (278 +/- 123 mm Hg to 67 +/- 13 mm Hg, P < .05) and intrapulmonary shunt increased (12.9% +/- 1.1% to 28.2% +/- 11.4%, P < .05) after endotoxin. Pretreatment with U-74389G attenuated the decrease in PO2 (476 +/- 61 mm Hg to 226 +/- 143) and the increase in intrapulmonary shunt (12.6% +/- 6.1% to 14.3% +/- 6.8%) observed after endotoxin. The extent of lung injury and systemic hemodynamics were similar between control or U-74389G-treated dogs. CONCLUSIONS: A free-radical-scavenger can attenuate the gas exchange defect commonly associated with endotoxin but it does not improve the derangement of systemic hemodynamics. PMID- 7889134 TI - Effects of N-acetylcysteine in endotoxic shock. AB - PURPOSE: The release of oxygen-free radicals has been implicated in both peripheral vascular and myocardial alterations of septic shock. N-Acetylcysteine (N-AC), a substrate for the production of glutathione, has potent antioxidant effects. As a nitrosothiol, it may also improve capillary blood flow. We studied the effects of N-AC in a dog model of endotoxic shock. METHODS: Ten pentobarbital anesthetized, mechanically ventilated dogs were randomly assigned to receive either N-AC (150 mg/kg loading dose in 1 hour, followed by 20 mg/kg.h maintenance dose) or D5W. After the loading dose, each dog received 3 mg/kg Escherichia coli endotoxin intravenously. After 30 minutes, saline infusion was started to restore and maintain baseline filling pressures. RESULTS: The loading dose of N-AC increased DO2 significantly (from 661 +/- 54 to 914 +/- 190 mL/min, P < .05), but VO2 remained stable. After the administration of endotoxin, fluid challenge restored cardiac output to baseline, in both groups. Hemoglobin and, thus, DO2 were slightly lower in the N-AC-treated dogs, but VO2 was similar in both groups. At the end of the study, O2ER was significantly higher in the N-AC-treated dogs than in the control dogs. Blood lactate levels fell more rapidly in the N-AC dogs than in the control dogs. Blood lactate levels returned to normal in the N-AC dogs but not in the control dogs. Tumor necrosis factor (TNF) also decreased significantly in the N-AC dogs but remained elevated in the control dogs. CONCLUSION: These data indicate that N-AC administration in endotoxic shock is well tolerated, may increase oxygen availability to the tissues, and is associated with an attenuation of TNF release. PMID- 7889133 TI - Value of elementary, combined, and modeled hemodynamic variables. AB - PURPOSE: It has been well recognized that the usefulness of the clinical examination and simple hemodynamic variables in the critically ill is limited. Modelization for hemodynamic analysis may improve the diagnostic performance by a systematic and multivariate analysis. This requires a rigorous formalization that may otherwise expand the usefulness of hemodynamic data, both as predictors and as therapeutic targets. Our study was designed to test the value of a model for assessing the pathophysiology of circulatory disorders and for establishing the diagnosis. METHODS: We tested all available variables using survival as the end point. A population of 223 patients (652 measurements) with compromised circulatory status was studied. We evaluated traditional variables: (1) morphological and physical data, (2) elementary right heart catheterization data, and (3) usually calculated variables, versus (4) new modeled variables. These new modeled variables were derived from a previously validated computer program for hemodynamic evaluation. They expressed differences between observed hemodynamic performance and estimated needs. RESULTS: Among traditional variables, major prognostic factors were: (1) in all patients, lactate level elevation, physical signs of hypoperfusion, and a decreased systemic arterial pressure; (2) in septic patients, a high PaO2/SaO2 ratio; (3) in nonseptic patients, low left ventricle work indices. In all cases, modeled hemodynamic variables assessing performance needs adequacy enhanced the prognostic value of hemodynamic monitoring. CONCLUSIONS: Compared with traditional variables, modeled variables were found of greater interest to quantify pathophysiology of shock. These results enabled us to validate the initial step of the hemodynamic reasonning formalization and to develop "new" diagnostic criteria that more closely fit the interrelationship between pathophysiology, diagnosis, and prognosis. PMID- 7889135 TI - Mechanisms of myocardial depression after bolus injection of sodium bicarbonate. AB - PURPOSE: The classic model for the effects of NaHCO3 on myocardial function predicts transient myocardial depression after an intravenous bolus of sodium bicarbonate in association with myocardial acidosis. METHODS: Five anesthetized, paralyzed, and ventilated dogs underwent midline sternotomy. Myocardial global function was assessed by cardiac output, left ventricular (LV) dp/dt, LV end systolic, and LV end-diastolic pressures. Regional myocardial function assessed by measuring the LV regional end-systolic, LV end-diastolic lengths, and LAD coronary blood flow. Coronary sinus, intramyocardial and arterial pH were measured as was free serum Ca++. Animals were made acidemia by infusion of 0.3 N HCl and then given a bolus of sodium bicarbonate. This produced transient depression followed by recovery of myocardial function. RESULTS: During the depression phase there was no significant decrease in interstitial pH or an increase in A-VCO2 difference as predicted by the current model. However, there was a significant decrease in the serum free Ca++ that coincided with myocardial depression. CONCLUSION: We could not confirm the predictions of the classic model and hypothesize that myocardial depression may be caused by decreased availability of free Ca++ of decreased Ca++ flux rather than intracellular acidosis. PMID- 7889136 TI - Endothelial and vascular smooth muscle function in sepsis. AB - The vascular abnormalities that arise during sepsis imply disturbances in the delicately tuned homeostatic mechanisms of vascular endothelium and smooth muscle. In the microvasculature, smooth muscle tone represents a complex equilibrium among metabolic stimuli, hemodynamic forces, and neurohumoral influences. Local tissue perfusion also is modulated by vasoactive mediators that can be produced locally, through endothelium-dependent adhesion and activation of inflammatory cells, or at a distance. In sepsis, derangement of normal autoregulation of perfusion, together with toxic effects of mediators, may be severe enough to result in organ dysfunction. Recent advances in vascular biology have illuminated a variety of targets, such as adhesion molecules, platelet activating factor, and inducible nitric oxide synthase for potential therapeutic intervention in sepsis. PMID- 7889137 TI - Red cell transfusion for elective surgery: a suitable case for treatment. PMID- 7889139 TI - Risk of hepatitis C in patients who received blood from donors subsequently shown to be carriers of hepatitis C virus. AB - A retrospective study was undertaken to identify recipients of blood from donors subsequently shown to be positive for hepatitis C virus using second-generation tests and polymerase chain reaction. The main aims were to determine the numbers of such recipients who were still alive and traceable, and to determine the risk of infection in this group. The feasibility and workload of this procedure, which is currently not practised in the U.K. or U.S.A., was also assessed. In the first six months of routine testing 42,697 donors were tested. Of 20 confirmed to be HCV-positive, 15 were regular donors. Eighty-three components were prepared from 63 anti-HCV positive previous donations from these donors. In all, nine recipients were found to be alive. All were positive for anti-HCV. We conclude that although this retrospective procedure is time-consuming and difficult, substantial numbers of infected recipients can be identified. The availability of treatment for chronic hepatitis C for such patients should encourage transfusion services to reassess current policies on the hepatitis C retrospective. PMID- 7889138 TI - Use of blood products for elective surgery in 43 European hospitals. The Sanguis Study Group. AB - The objective of this study was to assess the use of blood products and artificial colloids in six commonly performed elective surgical procedures in 43 teaching hospitals in 10 European countries. 7,195 patient data were analysed. For each product wide differences were found between hospitals, both in the proportion of patients transfused and the amount of product used for the same patient category. Adjustment for age, gender, preoperative haematocrit and blood loss, left major differences among hospitals in patient red unit transfusion. Hospitals in the Mediterranean area used less albumin and artificial colloids and more autotransfusion than those of central-northern Europe. The reasons for perioperative red cell transfusion were stated in the patient's medical record for 23% of patients. The ratio of preoperative blood request to transfusion was maximal in cholecystectomy, where it exceeded 10. The documentation of blood request and transfusion, and of transfusion complications in medical records, did not fully agree with that in the transfusion service in 49, 53 and 92% of the hospitals, respectively. The wide differences in blood product used for the same patient category were due to a variety of causes of which only some could be explained by the clinical factors taken into account. This suggests that consensus conferences and guidelines have so far had a limited impact on transfusion practice in many clinical units, even in teaching environments. PMID- 7889140 TI - Antenatal management of fetomaternal alloimmune thrombocytopenia--report of 15 affected pregnancies. AB - The recognition that spontaneous intracranial haemorrhage (ICH) may occur in utero in fetomaternal alloimmune thrombocytopenia (FMAIT) led us to attempt to prevent this in 15 pregnancies of 11 women who had previously affected infants with FMAIT due to anti-HPA-1a. The antenatal management included fetal platelet transfusions and maternal steroids and/or high-dose intravenous immunoglobulin (IVIgG). In the first pregnancy, ICH occurred between 32 and 35 weeks' gestation before any treatment had been given, emphasizing the need for earlier intervention. Five of the 14 subsequent pregnancies in this study were considered to be severely affected (severe haemorrhagic complications in a previous infant and initial fetal platelet count < 20 x 10(9)/L in this study); four were managed successfully with weekly fetal platelet transfusions started between 18 and 29 weeks and continued until delivery at 33-35 weeks, and one severely affected case who was referred at 36 weeks was managed successfully with a single platelet transfusion prior to delivery. Five pregnancies were considered to be mildly affected (previous infants were unaffected by severe bleeding and initial fetal platelet count > 50 x 10(9)/L in this study). The platelet counts were maintained in one case with steroids and in three with IVIgG without the need for repeated platelet transfusions, but in the fifth the fetal platelet count fell despite steroids and IVIgG and serial platelet transfusions were required. Four pregnancies were unsuccessful; two pregnancies were terminated after severe ICH occurred at an early stage before fetal blood sampling had been carried out, one fetus died after the mother had a severe fall despite the successful initiation of fetal platelet transfusions and one died due to a cord haematoma which occurred at the time of the initial fetal blood sampling. The optimal management of FMAIT to reduce the risk of antenatal ICH remains uncertain. Steroids and IVIgG may be effective in some mildly affected cases but serial fetal platelet transfusions are the preferred therapy for those who are severely affected. PMID- 7889142 TI - Rapid detection of Rh(D)- or K-positive fetal red cells in chorion villus samples by a flow cytometric technique. AB - Rh(D)- and K-negative women who have become severely isoimmunized by pregnancy are at risk of fetal loss or damage in subsequent pregnancies. A flow cytometric method is described whereby the presence of Rh(D) or K antigen on fetal erythrocytes may be determined using chorion villus samples taken during the first trimester. This method has the advantage of speed and sensitivity with results being available within 2 h. Decisions as to management of the pregnancy or termination may thus be made with minimal delay. PMID- 7889141 TI - Maternal intravenous immunoglobulin treatment does not prevent intracranial haemorrhage in fetal alloimmune thrombocytopenia. AB - In fetal alloimmune thrombocytopenia (FAIT) the fetus is threatened by intracranial haemorrhage (ICH); therefore early diagnostic and therapeutic intervention is required. We followed the clinical course of a 30-year-old woman during her fifth pregnancy after she had given birth to a child with alloimmune thrombocytopenia due to anti-Zwa. The fetus was monitored by 13 fetal blood samplings (FBS) always followed by transfusion of either maternal or compatible donor platelets. Intravenous immunoglobulin (ivIg) treatment of the mother was begun at 20 weeks of gestation when the fetal platelet count was 36 x 10(9)/l. The fetal platelets were typed Zwa positive by DNA analysis. Despite 11 weeks of maternal ivIg treatment fetal platelet counts progressively declined to 6 x 10(9)/l and ICH occurred. Subsequently, the fetus was successfully managed by intrauterine platelet transfusions at shorter intervals (3-5 days) and elective Cesarean section was carried out at 35 weeks of gestation. We conclude that maternal ivIg treatment does not prevent ICH in FAIT. The treatment of choice for severely affected cases is serial FBS combined with transfusion of compatible platelets. PMID- 7889143 TI - Polyamines to target drugs to DNA. AB - In neutral solutions polyamines are fully protonated, and hence are really polyammonium cations (PAC). Spermine, for example, carries four positive charges in a linear system, H3N+(CH2)3N+H2(CH2)4N+H2 (CH2)3N+H3. There is a very powerful coulombic interaction between aqueous DNA and such cations, thus the cations are attracted to the DNA over large distances, and once close to the DNA normally remain there for long periods. A key issue is; are the cations mobile, or do they remain at one preferred site for significant periods? The latter is the currently preferred concept, but NMR and EPR evidence will be presented in favour of the former. If the former is correct, then PACs may be able to act as good drug delivery systems. In its simple form the concept is that any drug that acts directly on DNA can be chemically bound to a PAC. Once in the cell, this PAC-drug complex (PAC-D) will be carried to DNA and will move very rapidly along the exposed strands until it recognises the site of action. This may be some special base sequence region, a damaged site, or the PAC-D unit may simply be present prior to potential damage, so that this can be repaired very rapidly. Some of our current studies on these systems are described. PMID- 7889144 TI - Decay studies of DMPO-spin adducts of free radicals produced by reactions of metmyoglobin and methemoglobin with hydrogen peroxide. AB - The 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) spin adduct of myoglobin (Mb) or hemoglobin (Hb) was formed when metmyoglobin (MetMb) or methemoglobin (MetHb) reacted with H2O2 in the presence of DMPO, and both decayed with half-life of a few minutes. The DMPO spin adduct of Mb decayed with biphasic kinetics with k1 = 0.645 min-1 and k2 = 0.012 min-1, indicating that the spin adduct consisted of two kinetically heterogeneous species, stable and unstable ones. The DPMO spin adduct of Hb, however, was homogeneous. Decay of both spin adducts was accelerated in the presence of tyrosine, tryptophan or cysteine, but not phenylalanine, methionine or histidine. The decay obeyed the first order kinetics at varying concentrations of the spin adducts. The decay was accelerated by denaturation and proteolysis of protein moiety. The decay rate was not affected by the extra addition of MetMb or MetHb to each spin adduct. The decay rate of the spin adduct of Mb was increased by hematin in the presence of H2O2 and decreased by catalase. Decay of stable spin adduct of Mb, however, was not significantly changed under any experimental conditions used. These results led us to conclude that instability of the DMPO-spin adducts of Mb and Hb is due to intramolecular redox reactions between the spin adducts and amino acid residues and/or products of the reaction between heme and H2O2. PMID- 7889146 TI - Effect of hypoxia-reoxygenation on peroxisomal functions in cultured human skin fibroblasts from control and Zellweger syndrome patients. AB - To delineate the role of peroxisomes in the pathophysiology of hypoxia reoxygenation we examined the functions of peroxisomes and mitochondria in cultured skin fibroblasts from controls and from patients with cells lacking peroxisomes (Zellweger cells). The loss of peroxisomal functions (lignoceric acid oxidation and dihydroxyacetonephosphate acyltransferase [DHAP-AT] activities) in control cells following hypoxia and hypoxia followed by reoxygenation, suggests that peroxisomes are sensitive to oxidative injury. The sensitivity of peroxisomes to oxidative stress was compared to that of mitochondria by examining the oxidation of palmitic acid (a function of both mitochondria and peroxisomes) in control and Zellweger cell lines, following hypoxia-reoxygenation. The greater loss of activity of palmitic acid oxidation observed in control cells as compared to that seen in Zellweger cells suggests that the peroxisomal beta-oxidation system is relatively more labile to hypoxia-reoxygenation induced oxidative stress. This data clearly demonstrates the difference in the response of mitochondria and peroxisomes to oxidative stress. PMID- 7889145 TI - Oxidant-induced activation of protein kinase C in UC11MG cells. AB - Free radical formation and subsequent lipid peroxidation may participate in the pathogenesis of tissue injury, including the brain injury induced by hypoxia or trauma and cardiac injury arising from ischemia and reperfusion. However, the exact cellular mechanisms by which the initial oxidative insult leads to the ultimate tissue damage are not known. A number of reports have indicated that protein kinase C (PKC) may be activated following oxidative stress and that this enzyme may play an important role in the steps leading to cellular damage. In this work, we have examined in a cell model whether PKC is activated following oxidative exposure. UC11MG cells, a human astrocytoma cell line, were treated with H2O2. Incubation with 0.5 mM H2O2 increased malondialdehyde levels by as early as 15 minutes. To assess the effects of H2O2 treatment on PKC activation, we measured phosphorylation of an endogenous PKC substrate, the MARCKS (myristoylated alanine-rich C kinase substrate) protein. Treatment of cells with 0.2-1.0 mM H2O2 resulted in a rapid increase in MARCKS phosphorylation. Phosphorylation was stimulated approximately 2.5-fold following treatment with 0.5 mM H2O2 for ten minutes. Treatment with phorbol 12-myristate 13-acetate, a PKC activator, increased MARCKS phosphorylation approximately 4-fold. The H2O2 induced MARCKS phosphorylation was inhibited by the addition of the kinase inhibitors H-7 and staurosporine. Furthermore, specific down-regulation of PKC by phorbol ester also inhibited H2O2-induced MARCKS phosphorylation. These results indicate that PKC is rapidly activated in cells following an oxidative exposure and that this cell system may be a good model to further investigate the role of PKC in regulating oxidative damage in the cell. PMID- 7889148 TI - Vitamin C at concentrations observed in premature babies inhibits the ferroxidase activity of caeruloplasmin. AB - High concentrations of total vitamin C have been measured in the plasma of premature infants. At these concentrations ascorbic acid inhibited the ferroxidase activity of caeruloplasmin measured directly in vitro. The degree of inhibition was dependent on the ratio of ascorbic acid: caeruloplasmin. Values for the ratio of vitamin C: caeruloplasmin measured in premature babies would be predicted to inhibit ferroxidase activity by up to at least 80%. Ferroxidase activity measured in the plasma of premature babies increased from birth but was significantly lower than in plasma collected from adults (< 0.001). Plasma ferroxidase activity was correlated with plasma caeruloplasmin concentration and, in premature babies only, showed a negative correlation with the ratio of vitamin C to caeruloplasmin. High levels of vitamin C in premature babies may compromise antioxidant mechanisms and exacerbate oxidant damage. PMID- 7889147 TI - Reactions of nitric oxide with nitronyl nitroxides and oxygen: prediction of nitrite and nitrate formation by kinetic simulation. AB - Nitric oxide reacts with nitronyl nitroxides (NNO) to form imino nitroxides (INO) and this transformation can be monitored using electron spin resonance spectroscopy. Recently, Akaike et al., reported that NNO such as 2-phenyl-4,4,5,5 tetramethylimidazoline-3-oxide-1-oxyl (PTIO) and its derivatives (e.g., carboxy PTIO) react with nitric oxide (.NO) in a 1:1 stoichiometry forming 2-phenyl 4,4,5,5-tetramethylimidazoline-1-oxyl (PTI) or the respective product (e.g., carboxy-PTI) together with nitrite and nitrate (Akaike et al., Biochemistry 32, 827-332, 1993). In this paper, we reevaluate their results and show that the stoichiometry of the reaction between PTIO and .NO is 0.63 +/- 0.06:1.0. The reason for this discrepancy is due to an erroneous assumption by Akaike et al., that the stoichiometry for the reaction between .NO and O2 is 2:1 in aqueous solution. If the data reported by Akaike et al., were recalculated using a 4:1 stoichiometry established for the aqueous oxidation of .NO, the reaction between .NO and PTIO would give a stoichiometry of 0.5:1.0 in closer agreement with our data. We propose mechanism for the reaction between PTIO and .NO in aqueous solution. This mechanism predicts that the stoichiometry between carboxy-PTIO and .NO is dependent on the rate of generation of .NO and is 1:1 only at low rates of .NO generation (i.e., 10(-13) M/s). However the stoichiometry approaches 0.5:1.0 at higher rates of .NO production or when it is added as a bolus. The ratio between nitrite and nitrate also varies as a function of the rate of generation of .NO. The model agrees with previous experimental observations that the aqueous oxidation of .NO in air saturated solutions will exclusively form nitrite and predicts that .NO will only generate substantial amounts of nitrate if it is released at a rate less than 10(-17) M/s. This may have important consequences in cellular systems where the concentration of .NO is typically measured from nitrite production. PMID- 7889149 TI - N,N'-bis-dibenzyl ethylenediaminediacetic acid (DBED): a site-specific hydroxyl radical scavenger acting as an "oxidative stress activatable" iron chelator in vitro. AB - During oxidative stress, iron traces are supposed to be released from normal storage sites and to catalyse oxidative damage by Fenton-type reactions. This type of damage is difficult to prevent in vivo except by the use of strong iron chelators such as deferoxamine (affinity constant for Fe(III): log K = 30.8). However, strong iron chelating agents are also suspected to mobilize iron from various storage and transport proteins thereby leading to toxic effects. In contrast, N,N'-bis-dibenzyl ethylenediaminediacetic acid (DBED) is an iron chelator with relatively low affinity for iron (affinity constant for Fe(III): log K < 15). In the present paper, we show that, in situations mimicking oxidative stress in vitro, DBED is site-specifically oxidized into new species with strong iron binding capacity. Indeed, in the presence of ascorbate as a reductant, the iron chelate of DBED reacts with H2O2 in aqueous solution to yield a purple chromophore with minor release of free HO. in the medium, as measured by aromatic hydroxylation assay. The formation of these purple species is not suppressed by the presence of HO. scavengers at high concentration. The visible spectrum of these species is consistent with a charge transfer band from a phenolate ligand to iron. N-2-hydroxybenzyl N'-benzyl ethylenediaminediacetic acid (HBBED) was identified in the medium as one of the oxidation products of DBED. Therefore, these results suggest that the iron chelate of DBED undergoes an intramolecular aromatic hydroxylation by HO. leading to 2-OH derivatives and hence that DBED is a site-specific HO. scavenger. Moreover, since the measured affinity for Fe(III) of HBBED (log K = 28) is at least 13 orders of magnitude higher than that of DBED and since ferric HBBED chelate is not a catalyst of Fenton chemistry, DBED may be looked as an "oxidative stress activatable" iron chelator, e.g. which increase in affinity for iron is triggered in the presence of H2O2 and an electron donor. Therefore it is proposed that DBED and related derivatives may be interesting as protective compounds against oxygen radicals toxicity, especially for chronic use. PMID- 7889150 TI - Radical exchange reactions between vitamin E, vitamin C and phospholipids in autoxidizing polyunsaturated lipids. PMID- 7889152 TI - [The xenogeneic transplantation of embryonic nerve tissue (the morphological and immunological aspects)]. AB - An analysis of the morphological and immunological aspects of xenotransplantation has shown that the xenotransplantation is a model for investigation of a wide range of problems of neurobiology: specific immune reactions in the brain and mechanisms of its immune privilege, conditions facilitating the take of transplants and mechanisms underlying autoimmune diseases of the CNS when the degenerative phase of the disease is accompanied by a cellular immune response. The use of xenotransplantations for studying potencies of the embryonic nerve tissues of man allowed to give grounds and to practically employ the method of treatment of parkinsonism. The first results of clinical use of the method obtained at the Institute of Experimental Medicine have shown its positive effects. PMID- 7889151 TI - [The topographical characteristics of the blood vessels of the human spine]. AB - Methods of roentgen angiography, injections of India ink-gelatin mass, morphometry, microscopy and others were used in an experiment carried out on non fixed corpses of children and adults for studying functional topography of arteries and veins of the vertebral column. Posterior intercostal and lumbar arteries were established to give off 3-4 anterior and 3-5 lateral branches from each side which penetrate into paradiscal segments of the vertebral body. In 92% one lateral branch runs downwards to the intervertebral disc and lower vertebra. Great number of vertical branches of various diameters come off from intraorganic arteries of horizontal orientation of paradiscal segments to intervertebral discs. The medial segment contains distinct basivertebral, anterior and lateral veins falling into venous plexuses surrounding the vertebrae. The diameter of these veins depends on specific properties of angiotopography, sizes and shape of the vertebra. The regular trends in question aid to explain the question of pathogenesis of hematogenic lesions of the vertebrae and to choose the methods of osteoplastic operations. PMID- 7889153 TI - [Changes in the duodenal glands with a modification of the diet (a histochemical study using lectins)]. AB - A set of lectins with different carbohydrate specificities were used for a histochemical analysis of the duodenal glands of rats which had different food rations during 3 months. Lectin receptors in glandulocytes of the duodenum had different spectra under different food regimens: protein diets of the animals correlated with the accumulation of glycopolymers in the glandular epithelium with the terminal residues of N-acetyl-D-galactosamine, N-acetyl-D-glucosamine, L fucose, higher content of cellulose in food was followed by reduction of fucosoglycans in combination with accumulation of mannose-containing glycopolymers. The regular specific features found point to quantitative and qualitative changes to the formed secretion of the duodenal glands under the influence of changing conditions of nutrition. PMID- 7889154 TI - [Body mass composition in athletes]. AB - Materials on main parameters of body mass of 14 sportsmen obtained by the authors and taken from foreign literature are presented. Parameters 4-20,2% for men and 10-29% for women should be used for the assessment of normal fluctuations of the fat component. PMID- 7889155 TI - [The cells of the liver sinusoid vessels]. PMID- 7889156 TI - [The charter of the independent Association of Morphologists]. PMID- 7889157 TI - [The structure of the hyaline cartilage in the plastic substitution of articular surface defects (an electron microscopic study)]. AB - Results of the transplantation of the hyaline (articular) cartilage with the subchondral layer were studied in 100 mature rabbits. The transplants were treated by different methods. It was found that the hyaline cartilage of the articular transplants does not take part in reparative processes. It undergoes either partial or complete resolution. The resolution processes in auto- or allotransplantation of fresh transplants proceed longer and are characterized by gradual death of cell elements and by a destruction of the collagen structures. The demineralized osteochondrous transplants preserved in a week solution of formalin with kanamycin are closer to them in their terms and character of transformation. They are the material which should be recommended as most perspective for arthroplasty. PMID- 7889159 TI - [The secretory activity of the large-cell hypothalamic nuclei in the humpback salmon Oncorhynchus gorbuscha Walbaum (Salmonidae) during the transition from sea to river and the reverse]. AB - Nuclei of the hypothalamus of Oncorhynchus gorbuscha Walbaum (Salmonidae) were studied morphologically after passing from the sea to the river at the period of spawning migration and then after the artificial carrying of the fish adapted to fresh water back to the sea. It was found that in peptidergic nuclei of the thalamus during first hours in fresh water there occurs activation of both the synthesis and evacuation of neurosecretion. In the preoptic nucleus the synthesis is activated in perikaryons of all the cells simultaneously, the cells being involved in elimination of the secretion in turn. In the lateral nucleus the secretion elimination takes place simultaneously in all the cells while signs of increased synthesis made their appearance later. By the end of the first day in fresh water both the synthesis and secretion in both nuclei are decreased. After the artificial carrying of gorbuscha back to the sea the preoptic nucleus is first activated and then, 1 day later, there appear signs of decreased activity. Soon after that they die. The lateral nucleus is not active after the artificial carrying of gorbuscha to the sea. Comparison of the results obtained with literature data shows that the preoptic nucleus of salmon reacts specifically to different extreme conditions and not by the type of universal stress-reaction as most vertebrates. PMID- 7889158 TI - [The proliferative processes in the skeleton of white rats administered dipal experimentally and after antioxidant therapy with tocopherol]. AB - Specific features of osteogenesis under a toxic action of pesticide Dipal and antioxidation therapy with tocopherol were studied in experiments in inbred albino rats by the method of autoradiography with 3H-thymidine label. The index of labeled nuclei and intensity of the label in chondroblasts and osteoblasts of the epiphyseal cartilage and periosteum of the middle third of the tibia diaphysis were counted in the light autoradiograms. The method of electron autoradiography was used for the identification of DNA-synthesizing osseous and cartilaginous cells and for studying their ultrastructure. The age-related and topographic activity of the proliferative osteogenic processes, their correlation with the degree of the toxic injury of the organism was established. Dipal, as an osteotropic drug, inhibits proliferative processes in the blast osseous and cartilaginous cells, sharply decreasing the index of labeled nuclei and the label intensity. Correction with tocopherol levels the degree of processes of the inhibition of osteogenesis. PMID- 7889160 TI - [Serotoninergic nerve fibers in the area of the substantia grisea and the ependyma of the cerebral aqueduct]. AB - An electron microscopic study of the midbrain gravy with the help of degeneration caused by serotonin-like neurotoxin 5,7-dihydroxytryptamine has shown that serotonergic terminals are responsible for the innervation of dendrites, neuron bodies and ependyma cells of the cerebral aqueduct. The detection of light, dark with prevailing fine transparent or large granular synaptic vesicles as well as vacuole degeneration evidences of the existence of several sources of serotonergic innervation of the central gray substance. Continuous damage of perivascular astrocytes of the central gray by neurotoxin allows a suggestion to be made that they are also the object of serotonergic innervation. Immunomorphological data on the presence of serotoninergic neurons in the cerebral gray are confirmed. PMID- 7889161 TI - [The nerves of the paravasal fatty tissue of the human iliac vessels]. AB - The aim of the work was to concretize ideas of the anatomy of extraintramural nerve plexuses along the course of large iliac vessels. Three nerves with the diameter 0.6-2 mm were revealed running from the iliac plexus to the paravasal fat. Topographic anatomical characteristics of these formations and their interrelations with the well-known branches of the lumbar plexus are given with special reference to practical value of the results obtained. The relation of nerves of the paravasal fat to adventitia of the vessels, lymph nodes, fascial and muscular formations was studied. PMID- 7889162 TI - [Myocyte proliferation and differentiation in experimentally induced myocardial hypertrophy]. AB - Processes of proliferation and differentiation of cardiomyocytes in control and during the low-temperature incubation of chicken embryos were studied by methods of radiography, cytophotometry, electron microscopy. In normal embryos at different periods of their development in histogenesis of the cardiac muscle tissue of chicken embryos there are periods with prevailing processes of proliferation, dynamic balance of processes of proliferation and differentiation and prevailing processes of differentiation of cardiomyocytes. Under conditions of developing hypertrophy of the myocardium, the regular processes of the development of organization of the myocardium at the cellular and tissue levels remain unchanged as a whole, but they shift in time. The urgent reaction of cardiomyocytes of the embryonic myocardium in the absence of formed tissue mechanisms of regulation of homeostasis is insufficient for the development of the compensation-adaptation and regulation processes in the cardiac muscle tissue, which might be responsible for the development of tissue according to the pathologic type. PMID- 7889163 TI - [The independent Association of Morphologists. The forms and methods of its operation]. PMID- 7889164 TI - [The structure and mechanical properties of the human pulmonary trunk and its valves]. AB - The histological structure and mechanical properties of the pulmonary trunk and its valves were studied in 35 complexes of the pulmonary artery of man. The valvular apparatus of the pulmonary trunk is formed by anatomical elements with different morphological structures. In it there are elements which might be considered from standpoints of biomechanics as membranous (pulmonary trunk, sinuses, cusps) and shaft (fibrous ring, commissural shafts, arcuate crests) elements, the commissural shafts representing a combination of structures forming a closed spatial inter-related construction--a natural elastic framework of the pulmonary trunk root and the sheath elements are morphologically interrelated and fixed on this framework. The mechanical properties of these shaft elements are formed not only at the expense of inclusion of other formations in their structure but also at the expense of changes in the density of distribution and spatial orientation of main carrier structures of sheath elements attached to them. So, the strength and rigidity of the fibrous ring were associated not only with the presence of collagenous fibers and chondroid tissue n it, but also with the regular arrangement of collagenous fibers coming to it from the sinus. Similarly, the strength of arcuate crests was in many respects dependent on dense arrangement of longitudinally oriented smooth muscles. The amount of smooth muscles in the pulmonary trunk was 1.3 and 2 times higher than that of collagenous and elastic structures which allows the pulmonary trunk of man to be referred to arteries of muscular or mixed type. It points to the necessity to take into account the influence of muscle tone on mechanical behavior of the pulmonary trunk under physiological exercise. PMID- 7889165 TI - [A comparative ultrastructural and morphometric analysis of the smooth myocytes in the tunicae intima and media of the human fetal aorta]. AB - Transmission electron microscopy was used for studying the thoracic part of the aorta of 9 human fetuses of 20-28 weeks of development. In the medial tunic of the human fetus aorta there are smooth myocytes (SM) of the contractile and synthetic phenotypes. The latter are localized mainly in the inner part of the media. In the inner tunic there are also SM of the synthetic phenotype. With the help of processes they make contacts with endotheliocytes and processes of SM of the media. In the gaps between the subendothelial SM and endothelium there are particles of elastin which form the structure resembling an additional elastic membrane. It is reasonable to think that the migration of SM into the intima is a stage of normal development of the vessel associated with the adaptation to local hemodynamic conditions rather than an initial manifestation of atherosclerosis. PMID- 7889166 TI - [The effect of burn trauma on the microcirculatory bed of the human thalamus]. AB - Alterations in the microcirculatory bed of the thalamus resulting from thermal trauma manifest themselves as dystonia of the arteriolar-venular part of the microcirculatory bed, sharply decreased density of functionally active capillaries, area of their exchange surface and amount of blood in them. Clear distinctions are observed in stages of burn disease. At the stage of burn shock all morphometric parameters of the capillary bed are decreased in anterior, medial, ventro-lateral and posterior (pulvinar) nuclei of the thalamus. At the stage of toxemia in anterior and medial nuclei the parameters were at the level of the control group or even higher. On the contrary, in ventro-lateral and posterior nuclei they remained considerably lower as compared with control figures. It is likely to be associated with the fact that the pathways of pain, tactile and temperature sensitivity which are the first to react to burn trauma are switched over in these groups of nuclei. PMID- 7889167 TI - [The surgical anatomical characteristics of the ureteral arteries and veins in nephroptosis and defects requiring surgical correction]. AB - Specific features of blood supply and topography of the ureters in patients with nephroptosis, multiple arteries of the kidneys and ureteral duplication were established on the material of 42 preparations of the kidneys and ureters taken from corpses of people who died at the age from 20 to 78 years. Standard anatomical methods were used. It was shown that in people with nephroptosis at the sites of the approach of the upper ureter vessels, of cross of the ureters and the testicular (ovarian) and iliac vessels there are points of fixation around which the ureters undergo greatest deformities and might be responsible for disturbances of the urine outflow. The ureteral vessels are often involved in adhesions in the sites of deformities of the ureters. In cases with a duplication of the renal arteries as a rule have their beginning from the renal artery located below (72,2i%). With a greater distance between the beginning of the doubled renal arteries the upper ureteral arteries on one side, the lower artery of the kidney is located atypically (behind the inferior vena cava) and is not a source of blood supply of the ureter. In cases with a partial duplication (split) of the ureters in the abdominal part they are supplied with blood from the common source. PMID- 7889168 TI - Enantiomeric separation and determination of antiparkinsonian drugs by reversed phase ligand-exchange high-performance liquid chromatography. AB - A simple and rapid high-performance liquid chromatographic method for the separation and determination of enantiomers of levodopa and carbidopa using a LiChrosper C18 column with aqueous copper-L-phenylalanine as mobile phase was developed. The separation between D- and L-enantiomers of levodopa and carbidopa was fairly good with separation factors of 1.63 and 2.38, respectively. The method was validated using synthetic mixtures and used for quality assurance of commercial formulations. PMID- 7889169 TI - Importance of the alpha-amino group in the selective purification of synthetic histidine peptides by immobilised metal ion affinity chromatography. AB - The retention behaviour of some histidine containing peptides on Cu2(+)- and Ni2(+)-loaded immobilised metal ion affinity chromatography (IMAC) supports has been investigated and compared with that observed for the corresponding compounds lacking the free alpha-amino group and/or the imidazole function. On immobilised Cu2+ all histidine-containing peptides, including those with a blocked alpha amino function, were strongly retained above pH 5. The presence of a free alpha amino group increased the retention marginally. On immobilised Ni2+ histidine peptides with a free alpha-amino group were strongly bound with a maximal retention at pH 8.5. Blocking of the amino group or removal of the imidazole moiety reduced the maximal retention by a factor 5 to 10, with no retention observed for peptides lacking both histidine and a free alpha-amino group. These observations indicate the involvement of two equipotent attachment points in the binding. It seems that IMAC on a Ni2(+)-loaded support can be used for the purification of histidine containing peptides synthesised by the solid-phase method. Inclusion of a capping protocol in the synthesis ensures that a free alpha-amino group, which can be used as an affinity handle, will be present only on the target peptide. PMID- 7889170 TI - New markers of bone metabolism: clinical use in metabolic bone disease. PMID- 7889171 TI - Seeing T cells behind the eye. PMID- 7889172 TI - Analysis of retroorbital T cell antigen receptor variable region gene usage in patients with Graves' ophthalmopathy. AB - To date, it has remained unclear whether orbit-infiltrating T cells in patients with Graves' ophthalmopathy (GO) represent a primary immune response in which a limited number of T cell clones driving the disease are activated against specific antigens, or whether they participate in a non-specific inflammatory process. To characterize these T cells at the molecular level, we examined the T cell antigen receptor (TcR) V gene repertoire in situ in retroorbital tissue specimens obtained from patients with early and late stages of clinically severe GO and from patients with non-GO orbital conditions. Ribonucleic acid extracted from orbital tissue and peripheral blood lymphocytes (PBL) was reverse transcribed and amplified using the polymerase chain reaction and 22 V alpha and 24 V beta gene-specific oligonucleotide primers. The resulting TcR V alpha and V beta transcripts were verified by Southern hybridization analysis using TcR C region-specific, digoxigenin-labeled oligonucleotide probes. Compared with matched PBL, the retroorbital TcR V alpha and V beta gene repertoire expressed was heterogeneous, but revealed marked restriction of V gene usage in samples derived from retroorbital connective tissue and extraocular muscle of all eight patients with severe GO of short duration studied. In contrast, greater diversity of the TcR V beta gene repertoire and loss of TcR V alpha gene restriction was noted in four patients with late GO undergoing reconstructive eye muscle surgery. Unrestricted TcR V gene usage was demonstrated in orbital tissue and PBL samples obtained from control subjects. These results suggest that retroorbital TcR V gene usage is variable but markedly restricted during the earlier stages of GO. With increasing disease duration, greater diversity of the TcR V gene repertoire appears to develop, and oligoclonality of the T cell response may be lost. Selection of patients with early stages of GO will be important when further dissecting TcR usage and antigen specificity of orbit-infiltrating T lymphocytes in GO. PMID- 7889173 TI - Steroid-converting enzymes on the move. PMID- 7889174 TI - A case of 16-ene-synthetase deficiency in male pseudohermaphroditism due to combined 17 alpha-hydroxylase/17,20-lyase deficiency. AB - A 17-year-old phenotypic female with primary hypergonadotropic amenorrhea, absence of secondary sexual development, hypertension and 46 XY karyotype is presented. Hormonal analysis revealed very low levels of testosterone, dehydroepiandrosterone, androstenedione, estrogens, cortisol and high levels of ACTH, progesterone, deoxycorticosterone and corticosterone. Enzyme studies of the testicular tissue after bilateral gonadectomy showed absence of 17 alpha hydroxylase and 17,20-lyase activity as well as 16-ene-synthetase activity. This enzyme catalyzes the reaction from pregnenolone to 5,16-androstadien-3 beta-ol, a sex pheromone precursor. The other enzyme systems leading from pregnenolone to testosterone were intact. This is the first report of male pseudohermaphroiditism in which the combination of 17 alpha-hydroxylase, 17,20-lyase and 16-ene synthetase deficiency is described, indicating that all these activities might be associated with the same protein. PMID- 7889175 TI - Missense mutation in CYP11B1 (CGA[Arg-384]-->GGA[Gly]) causes steroid 11 beta hydroxylase deficiency. AB - Steroid 11 beta-hydroxylase deficiency (11 beta-OHD) is an autosomal recessive hereditary defect and one of the causes of congenital adrenal hyperplasia. The 11 beta-hydroxylase enzyme is encoded by the CYP11B1 gene on chromosome 8q22. Twelve types of mutations of this gene have been reported previously in patients with 11 beta-OHD, including one Japanese patient. We detected an additional previously uncharacterized mutation: R384G mutation, a single C-->G base substitution in the codon 384 of the exon 7 changing an arginine (CGA) to a glycine (GGA) by sequencing the CYP11B1 gene of Japanese siblings with 11 beta-OHD. We analyzed also the CYP11B1 gene of their unaffected family members. Their grandfather was homozygous for the normal gene, whereas their grandmother, parents and younger brother were heterozygous for the mutation. These results indicate that the cause of 11 beta-OHD is heterogeneous even in the Japanese population, which is ethnically homogeneous. PMID- 7889176 TI - What is the function of adrenal inhibins? PMID- 7889177 TI - In vivo and in vitro evidence for the production of inhibin-like immunoreactivity in human adrenocortical adenomas and normal adrenal glands: relatively high secretion from adenomas manifesting Cushing's syndrome. AB - To clarify whether adrenal gland secretes inhibin in vivo in physiological or pathological conditions, we measured the levels of inhibin-like immunoreactivity (inhibin-LI) in adrenal veins (A-vein) and compared them with those in inferior vena cava (IVC) using blood samples obtained at catheterization of adrenal vein in the patients with adrenal adenoma manifesting Cushing's syndrome (Cs), aldosterone-producing adenoma, clinically non-functioning adenoma and normal adrenal gland. The tumor sides of A-veins in the patients with adenomas and also both sides of A-veins in subjects with normal adrenal glands showed significantly higher contents of inhibin-LI than their IVC. When the inhibin-LI secretion rate from adrenal gland was estimated by the difference between the levels of A-vein (tumor side) and IVC, Cs adenomas showed the highest secretion rate. Similarly, the tissue inhibin-LI content and the basal secretion rate of inhibit-LI from primary cultured cells were the highest in Cs adenomas. These findings indicated that normal adrenal glands and adrenocortical adenomas produced and secreted inhibin-LI into the general circulation in vivo and Cs adenomas have relatively high capacity for secreting inhibin-LI, and the present study provided the first in vivo evidence for adrenal inhibin-LI production in pathological conditions. PMID- 7889178 TI - Percutaneous ethanol injection: what is its role in the management of nodular lesions of endocrine glands? PMID- 7889179 TI - Percutaneous computed tomography-guided ethanol injection in aldosterone producing adrenocortical adenoma. AB - The feasibility, safety and effectiveness of percutaneous computed tomography guided ethanol injection (PEI-CT) was investigated in a patient affected by aldosterone-producing adenoma (APA). A 42-year-old male patient with typical features of hyperaldosteronism presented a solitary left adrenal adenoma measuring 2 cm, with a normal contralateral gland, evidenced by both CT scan and adrenal [75Se-19]-nor-cholesterol scintigraphy. After normalization of potassium plasma levels, 4 ml of sterile 95% ethanol with 0.5 ml of 80% iothalamate sodium was injected. The procedure was completed in about 30 min. No severe pain or local complication was noted. Five hours after PEI, a fourfold and a twofold increase in aldosterone and cortisol plasma levels were observed, respectively. After 11 days on a normal sodium and potassium diet, normal potassium plasma levels and reduced aldosterone plasma levels were present, with reappearance of an aldosterone postural response. Plasma renin activity and aldosterone plasma levels normalized 1 month later, with reappearance also of a plasma renin activity postural response and maintenance of normal potassium plasma levels even on a high sodium and normal potassium diet. The patient has remained hypertensive, although lower antihypertensive drug dosages have been employed. After 17 months, normal biochemical, hormonal and morphological findings were still present. Thus, we suggest PEI-CT as a further alternative approach to surgery in the management of carefully selected patients with APA. PMID- 7889180 TI - Insulin-like growth factors I and II in healthy women with and without established osteoporosis. AB - We measured serum concentrations of insulin-like growth factors I and II (IGF-I and IGF-II) by radioimmunoassay in 107 healthy women aged 28-78 years and in 116 women with established osteoporosis. The women with established osteoporosis were randomized to a 1-year double-blind, placebo-controlled treatment with continuous estrogen/progestogen, anabolic steroids, salmon calcitonin or placebo and the IGFs were measured every 6 months. Women less than 35 years of age had 29% higher levels of IGF-I (p < 0.001) as compared to women above that age. For women more than 35 years of age, we found no correlation between IGF-I and age (r = 0.02). Correspondingly, we found no significant changes in serum IGF-I in 10 women, who were followed with serial measurements of IGFs every 3 months from 2 years before to 1 year after menopause; IGF-II revealed no correlation with age (r = 0.04). In the group of 116 women with established osteoporosis, IGF-I was 30% lower (p < 0.01) as compared to a group of 19 height-, weight- and age-matched nonfractured women (mean age 64 years). The IGF-II levels were equal in the two groups. Over the 1-year therapeutic intervention period, an increase in IGF-I of 13-15% (p < 0.05) was seen in the nandrolone decanoate-treated group. The same tendency was seen for hormone replacement therapy, although it was not significant. In conclusion, the serum level of IGF-I is high in young women, when peak bone mass is attained, and low in postmenopausal women with established osteoporosis. PMID- 7889182 TI - Dexamethasone therapy is associated with a rise in urinary epidermal growth factor concentrations in the preterm infant. AB - The effect of glucocorticoid hormones on epidermal growth factor (EGF) concentrations has not been described in the premature infant. We examined this relationship in a group of infants treated with dexamethasone for airway edema (three to five doses) or chronic lung disease (six weeks of a tapering protocol). We collected urinary samples in 45 infants (25 for airway edema, 20 for chronic lung disease) before, during and after the use of dexamethasone. The EGF values were unchanged in infants that were given dexamethasone for airway edema. In contrast, all infants treated for chronic lung disease increased their EGF values by 1 week of therapy. At the end of the dexamethasone taper, ten of the infants had recovered successfully from ventilatory support. This group of infants had post-therapy EGF values that were significantly higher than pretherapy values. In the ten infants that were still ventilator dependent at the end of therapy, EGF values were not different from pretherapy values. We conclude that dexamethasone therapy was associated with an increase in urinary EGF values in the preterm infant treated for at least 1 week. The positive correlation of tapering from ventilatory support with increases in EGF values suggests that EGF may be a marker of dexamethasone effect or an effector of dexamethasone action. PMID- 7889181 TI - Intramuscular injections of slow-release lanreotide (BIM 23014) in acromegalic patients previously treated with continuous subcutaneous infusion of octreotide (SMS 201-995). AB - Nine acromegalic patients (five females and four males), mean age 50 +/- 4 years, presented macroadenomas (N = 7), microadenoma (N = 1) or normal computed tomography scans (N = 1). Patients were treated with continuous subcutaneous infusion of octreotide (range 200-600 micrograms/day). Following a washout period of 7 days, the patients were injected im with 30 mg slow-release lanreotide every 10 days for the first month and then twice monthly. In case of elevated growth hormone (GH) levels at 3 months, the patients were injected every 10 days for the next three months. Plasma GH and insulin-like growth factor I (IGH-I) decreased in all patients during octreotide treatment. After 6 months of octreotide treatment, seven patients were considered as well controlled (mean 8 h GH < 5 micrograms/l, IGF-I normal) whereas in two patients the mean 8-h GH and/or IGF-I levels remained increased. Serum GH and IGH-I increased after octreotide withdrawal. In one patient, serum GH and IGF-I increased during slow-release lanreotide administration and injections were stopped after 45 days. After 3 months of lanreotide, three patients were well controlled while in five patients GH or IGF-I levels were not normalized. At 6 months, five patients were injected twice monthly and three patients had one injection every 10 days. Six patients were well controlled and in two patients the mean 8-h GH level remained increased. The pituitary tumor volume decreased by 20-30% in two patients during octreotide, as well as in one other during slow-release lanreotide therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889183 TI - Lack of evidence for pituitary thyrotroph down-regulation after 1 week of oral thyrotrophin-releasing hormone and metoclopramide under conditions of constant peripheral thyroid hormone levels. AB - We investigated the pituitary thyrotrophin (TSH) response to repeated oral (non pulsatile) thyrotrophin-releasing hormone (TRH) administration and potential modifying effects of dopamine antagonist treatment under conditions of constant peripheral thyroid hormone levels. In a randomized double-blind crossover trial, seven hypothyroid subjects, euthyroid on L-thyroxine, received 1 week each of oral TRH (40 mg, 12 hourly) plus metoclopramide (10 mg, 8 hourly) and TRH (40 mg, 12 hourly) plus placebo (one capsule, 8 hourly). At the beginning and end of each treatment period five samples of blood for estimation of serum TSH were taken over 1 h before ("baseline") and seven samples over 2 h after the treatment combination was given ("stimulated"). Serum free thyroxine, free triiodothyronine and prolactin levels also were measured. Mean log10 +/- SEM (log10 mIU/l) "baseline" serum levels TSH were -0.177 +/- 0.183 (median 0.345 mIU/l (untransformed); range (r) 0.03-10.11 mIU/l; first quartile (1q) 0.22 mIU/l; third quartile (3q) 2.48 mIU/l) before and 0.182 +/- 0.107 (median 1.385 mIU/l; r = 0.45-19.8 mIU/l; 1q = 0.9 mIU/l; 3q = 1.78 mIU/l) after 1 week of treatment (p < 0.02). There were no significant differences between oral TRH plus metoclopramide and oral TRH plus placebo. Peripheral thyroid hormone levels and the "stimulated" TSH response (expressed as area under curve after TRH and metoclopramide or placebo; min.log10 mIU/l) remained unchanged after 1 week. In the absence of changes in peripheral thyroid hormone levels, oral TRH over 1 week may not result in down-regulation of anterior pituitary thyrotrophs.2+ f2p4 PMID- 7889184 TI - Interpretation of growth hormone provocative tests: comparison of cut-off values in four European laboratories. AB - To compare interpretations of growth hormone (GH) provocative tests in laboratories using six different GH immunoassays (one enzymeimmunometric assay (EIMA, assay 1), one immunoradiometric assay (IRMA, assay 5), one time-resolved fluorimmunometric assay (TRFIA, assay 3) and three radioimmunoassays (RIAs, assays 2, 4 and 6)), aliquots of peak samples from GH provocative tests were distributed between the four participating laboratories, quantified in the respective immunoassays and interpreted according to the cut-off values for provocative tests defined for each assay method. There was a high degree of relative correlation between the different assays, but absolute GH estimates differed. Assays 2, 4, 5 and 6 yielded almost identical GH levels. Assays 1 and 3 yielded serum GH levels approximately 39% and 70%, respectively, of those of assays 2, 4, 5 and 6. Although the absolute GH level measured in the various assay methods varied, there was good agreement between the interpretation of a given sample among the participating laboratories. This indicates that the differences in estimates of serum GH concentration by different immunoassay systems can be compensated for when cut-off values are defined for each method. PMID- 7889185 TI - Antibodies against restricted sequences in human c-ErbA hinge domain recognize differentially natural mammalian alpha- or beta-type triiodothyronine receptors and interfere differently with hormone binding. AB - In our first report, rabbit antibodies directed to recombinant polypeptides of human alpha-type c-ErbA sequences recognized natural triiodothyronine (T3) receptors (TR) in adipocytes (mouse Ob 17 cell line) but not in liver (mouse, rat). Moreover, some of them, directed to the sequence 150-228, markedly interfered with hormone binding to adipocyte T3 receptors. We now raised antibodies against shorter synthetic peptides within this alpha-type 150-228 c ErbA sequence, which encompasses part of the hinge (D) domain and N-terminus of the E domain (alpha-150-166 and alpha 172-191) and against a beta-type c-ErbA sequence (beta 204-220 aligned on alpha 150-166, and differing by eight amino acids). Our present antibodies, which bear the expected c-ErbA alpha- or beta type specificity, immunoprecipitated the TR in nuclear extracts, with a different pattern between tissues: exclusive precipitation by anti-c-ErbA alpha antibodies in Ob 17 adipocytes; large but non-exclusive precipitation by anti-cErbA beta antibodies in rat or mouse liver, which also expresses some alpha-type TR. This pattern of discriminative immunoprecipitation, also obtained in parallel analysis using our previously described antibodies to other c-ErbA alpha or beta sequences (anti-alpha 144-162, anti-alpha 1 403-410 and anti-beta 62-82), roughly verifies results of c-erbA mRNA expression in these tissues. Slight differences appeared in the extent of alpha-type TR recognition by antibodies directed to alpha 172 191, whether TR were liganded or not to T3 before antibody addition. This evokes a different conformation of this region after hormone binding. Most interestingly, these anti-alpha 172-191 antibodies lowered the Ka for T3 and extensively dissociated the adipocyte T3-TR complexes; they interfered poorly with the binding of T3 in liver nuclear extracts. This strongly supports the concept that internal sequences in c-ErbA alpha, more precisely in a restricted C terminal part of the D domain, are necessary for efficient T3 binding, which also need the C-terminal part of domain E. PMID- 7889186 TI - Orchidectomy selectively increases follicle-stimulating hormone secretion in gonadotropin-releasing hormone antagonist-treated male rats. AB - The pituitary component of the feedback mechanisms exerted by testicular factors on gonadotropin secretion was analyzed in adult male rats treated with a potent gonadotropin-releasing hormone (GnRH) antagonist. In order to discriminate between androgens and testicular peptides, groups of males were orchidectomized (to eliminate androgens and non-androgenic testicular factors) or injected with ethylene dimethane sulfonate (EDS), a selective toxin for Leydig cells (to eliminate selectively androgens) and treated for 15 days with vehicle or the GnRH antagonist Ac-D-pClPhe-D-pClPhe-D-Trp-Ser-Tyr-D-Arg-Leu-Arg-Pro-D-Ala-+ ++NH2CH3COOH (Org.30276, 5 mg/kg/72 hours). Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured 7 and 14 days after the beginning of treatment. We found that: in males treated with GnRH antagonist, orchidectomy or EDS treatment did not induce any increase in LH secretion; and orchidectomy, but not EDS treatment, increased FSH secretion in GnRH-treated males. The present results show that negative feedback of testicular factors on LH secretion is mediated completely through changes in GnRH actions. In contrast, a part of the inhibitory action of the testis on FSH secretion is exerted directly at the pituitary level. It can be hypothesized that non-Leydig cell testicular factor(s) inputs at different levels of the hypothalamic pituitary axis in controlling LH and FSH secretion. PMID- 7889188 TI - Differences in insulin secretion between the rat and mouse: role of cAMP. AB - Although information regarding insulin secretion usually is considered equivalent when generated in the mouse or the rat, it is established that the kinetics of insulin secretion from mouse and rat pancreatic beta cells differ. The mechanisms underlining these differences are not understood. The in vitro perfused pancreas and isolated islets of the mouse or rat were employed in this study to investigate the role of cyclic adenosine monophosphate (cAMP), a major positive modulator of beta-cell function, as one differentiating signal for the uniquely different insulin release from the beta cells of these commonly used rodents. Glucose-stimulated first-phase insulin release from the perfused pancreas of the rat was higher than the mouse when calculated per gram of pancreas or as fractional secretion, but this phase was identical in the two species when results were adjusted for total body weight. Whether related to insulin content, pancreatic weight or body weight, the rat pancreas responded to glucose with a progressively increasing second-phase insulin release compared to the mouse pancreas, which secreted a flat second-phase of lesser magnitude. Isolated islets from rat and mouse were comparable in insulin content whereas the basal cAMP level of mouse islets was less than half that of the rat. At submaximal stimulation with glucose or glucose + IBMX or forskolin, mouse islets exhibited lower cAMP levels to a given stimulus than the rat. In rat islets cAMP levels increased to approximately 1000 fmol per islet, although insulin secretion maximized by 100-150 fmol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889187 TI - Effect of streptozotocin injection on expression of immunoreactive follistatin and beta A and beta B subunits of inhibin/activin in rat pancreatic islets. AB - The effect of streptozotocin (STZ) on expression of immunoreactive follistatin and beta-subunits of inhibin/activin in pancreatic islets was studied by immunohistochemistry. To localize immunoreactive follistatin in pancreatic islets, two different anti-follistatin sera were used. Anti-follistatin (300-315) serum detects only long-form follistatin, while anti-follistatin(123-134) serum detects both long- and C-terminal truncated short-form follistatin in sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. Although an intense reaction with anti-follistatin(123-134) was found in pancreatic B cells, a reaction with anti-follistatin(300-315) was not present in any type of cells. This result suggests that only short-form follistatin is expressed in pancreatic islets. It was confirmed that immunoreaction with anti-beta A(1-10) Tyr serum was found in pancreatic B cells. The anti-beta B(1-10)-Tyr reaction was intense in A cells but weak in B cells. These findings suggest that the expression pattern of each beta-subunit differs in each type of islet cells. At 2 weeks after STZ injection (65 mg/kg), insulin immunoreaction still remained in B cells, although most pancreatic B cells were destroyed. In contrast, immunoreactions of follistatin and beta-subunits in B cells disappeared 24h after STZ treatment. These results indicate that STZ affects the production of follistatin or beta-subunits of inhibin/activin in pancreatic B cells rather than insulin secretion. PMID- 7889189 TI - Angiotensin II Receptor Antagonists: Can they Go Beyond ACE Inhibitors? Proceedings of a satellite symposium to the 15th scientific meeting of the International Society of Hypertension. Melbourne, Australia, March 1994. PMID- 7889190 TI - Angiotensin II subtype 1 receptor modulates epinephrine release from isolated rat adrenal gland. AB - To elucidate the role of subtypes of the angiotensin (AT) II receptor in epinephrine release from the adrenal gland, the effects of AT II subtype 1 (AT1) receptor and AT II subtype 2 (AT2) receptor antagonists on AT II-induced modulation of epinephrine release were examined. Seven-week-old Wistar rats were used in this study. The left adrenal gland was perfused in a retrograde fashion. The effects of AT II on basal epinephrine release and epinephrine release by electrical stimulation were examined before and after treatment with CV-11974 (CV), an AT1 receptor antagonist, or PD123319 (PD), an AT2 receptor antagonist. AT II increased epinephrine release from the adrenal gland. CV almost completely suppressed AT II-induced increases in epinephrine release. In contrast, PD had no significant effects on AT II-induced increases in epinephrine release. These results suggest that AT II increases epinephrine release from the adrenal medulla via the AT1 receptor. PMID- 7889192 TI - Effects of an angiotensin II receptor antagonist, TCV-116, on insulin sensitivity in fructose-fed rats. AB - This study was designed to examine the effects of an angiotensin II receptor antagonist on insulin sensitivity in an insulin-resistant hypertensive rat model (fructose-fed rats; FFR). Male Sprague-Dawley rats were fed a fructose-rich diet or standard chow for 4 weeks and then treated with either 1 mg/kg/day of TCV-116 (angiotensin II receptor antagonist) or vehicle for a further 2 weeks. Steady state plasma glucose (SSPG) was measured while the animals were conscious. Insulin (2.5 mU/kg/min) and glucose (8 mg/kg/min) were simultaneously infused to determine insulin sensitivity in each group. The mean arterial pressure (MAP) was higher in the FFR (133 +/- 5 mmHg) than in the control group (120 +/- 3), and TCV 116 (110 +/- 4) decreased MAP significantly. SSPG was also higher in the FFR group (207 +/- 6 mg/dl) than in the control (137 +/- 10, p < 0.01), and TCV-116 (171 +/- 7) significantly reduced SSPG. The FFR group also had higher steady state plasma insulin (SSPI) levels than the control (107 +/- 10 microU/ml for FFR and 63 +/- 12 for control, p < 0.05), and TCV-116 attenuated the increase in SSPI (73 +/- 11, p < 0.05). Thus, the angiotensin II receptor antagonist improved insulin resistance, as assessed by determining SSPG in FFR, suggesting that angiotensin II antagonism may play an important role in improving of insulin resistance in FFR. PMID- 7889191 TI - Gene expression of the type-1 angiotensin II receptor in rat adrenal gland. AB - To evaluate the biosynthesis of the type-1 angiotensin II (AT1) receptor and the regulation of AT1 receptor subtypes in the rat adrenal gland, we performed non radioisotope in situ hybridisation histochemistry with an AT1 receptor complementary RNA (cRNA) probe and a messenger RNA (mRNA) probe. The levels of AT1A and AT1B receptor mRNAs were measured by the reverse transcriptase polymerase chain reaction method after 4-week treatment with a selective AT1 receptor antagonist, TCV-116, and an angiotensin-converting enzyme inhibitor, delapril. Specific hybridisation signals were observed with the cRNA probe in both the cortex and medulla of the rat adrenal gland. An especially strong signal was observed in the zona glomerulosa. TCV-116 did not affect the levels of expression of AT1A and AT1B receptor mRNAs in the adrenal gland. Delapril, on the other hand, significantly reduced the levels of expression of AT1A and AT1B receptor mRNAs. These results indicate that the sites of biosynthesis of the AT1 receptor are mainly distributed in the adrenal zona glomerulosa. The observed differences in levels of expression of AT1 receptor mRNAs following treatment with TCV-116 and delapril suggest the involvement of the AT2 receptor in the regulation of AT1 receptor subtypes. PMID- 7889193 TI - Effects of an angiotensin II receptor antagonist, TCV-116, on renal haemodynamics in essential hypertension. AB - The renal effects of a nonpeptide angiotensin II receptor antagonist, TCV-116, were investigated in 12 hospitalised patients with mild-to-moderate essential hypertension. After a 2-week placebo period, TCV-116 was given for 2 weeks in increasing doses from 4 mg to 8 mg daily to normalise the mean blood pressure. Blood pressure fell from 156 +/- 9/93 +/- 3 mmHg at the end of the placebo period to 140 +/- 9/85 +/- 4 mmHg after TCV-116 treatment. The pulse rate was unchanged. Renal vascular resistance fell from 1.62 +/- 0.20 to 1.37 +/- 0.17 dyne.s.cm-5 . 1.48 m2 x 10(4), renal plasma flow increased from 329 +/- 19 to 367 +/- 27 mL.min 1.1.48 m-2, and GFR was unchanged despite a fall in renal perfusion pressure. TCV 116 reduced the filtration fraction from 0.302 +/- 0.019 to 0.258 +/- 0.009, suggesting a preferential reduction in efferent arteriolar resistance. The fractional excretion of sodium, potassium, and urate did not change. An increase in plasma renin activity (from 1.1 +/- 0.3 to 2.2 +/- 0.7 ng.mL-1.h-1) and a fall in the plasma aldosterone concentration (from 6.2 +/- 0.8 to 4.5 +/- 0.7 ng.dL-1) were also seen. These results indicate that TCV-116 has favourable renal effects and a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. PMID- 7889194 TI - Effect of an angiotensin receptor antagonist, TCV-116, on sympathetic nerve activity in patients with essential hypertension. AB - The effects of an angiotensin II receptor (AT1) antagonist on sympathetic nervous responses to a mental arithmetic task and a cold pressor test were investigated using a placebo-controlled, single-blind design in 8 patients with essential hypertension (53 +/- 3 years). All patients received a placebo for 2 weeks (placebo run-in period), after which the control group (P; n = 4) continued to receive the placebo, while the experimental group (TCV; n = 4) received TCV-116 at 4 mg/day for 4 weeks (treatment period). After basal measurements were carried out, an arithmetic task and a cold pressor test were conducted on the last day of each period. Blood pressure (BP), heart rate (HR) and electrocardiogram (ECG) were continuously monitored. Muscle sympathetic nerve activity (MSNA) was assessed by determining the burst rate of the mean voltage neurogram obtained from the tibial nerve. Sympathovagal balance was also assessed, by determining the area ratio of the low frequency (LF: 0.05-0.15 Hz) to high frequency bands (HF: 0.16-0.5 Hz) of a power spectral analysis of HR variability (maximum entropy method). During the placebo run-in period, there were no significant differences in basal BP, HR, LF/HF or MSNA between the two groups. During the treatment period, basal mean BP in the TCV group was significantly lower (p < 0.05) than that in the P group, but there were no significant differences in basal HR, LF/HF or MSNA between the two groups. Although the arithmetic stress significantly increased BP, HR and LF/HF in both groups, MSNA was not significantly altered in either group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889195 TI - Role of the renin-angiotensin system in hypertension in the elderly. AB - Although the activity of the renin-angiotensin system is known to decrease with age, the antihypertensive efficacy of angiotensin-converting enzyme (ACE) inhibitors has been demonstrated in the elderly. To examine the role of the renin angiotensin system in hypertension in the elderly, we evaluated the antihypertensive response to enalapril and to TCV-116, an angiotensin II type-1 receptor antagonist, in elderly patients with essential hypertension. A single oral dose of enalapril (10 mg) increased plasma renin activity (PRA) and reduced the angiotensin II concentration, whereas a single oral dose of TCV-116 (4 mg) increased both PRA and the angiotensin II concentration. Blood pressure was significantly reduced by these drugs from 4 h after administration. Basal levels of PRA and angiotensin II declined with age. However, the changes in blood pressure produced by either TCV-116 or enalapril did not correlate with age. These results suggest that the activity of the renin-angiotensin system in plasma declines with age, and that the extrarenal renin-angiotensin system may play a role in hypertension in the elderly. PMID- 7889196 TI - Regional haemodynamic effects of the novel AT1 receptor antagonist, CV-11974, in conscious rats. AB - CV-11974, a newly developed angiotensin II (AII) subtype 1 (AT1) receptor antagonist, lowers mean arterial pressure (MAP) in various hypertensive animal models. The aim of this study was to examine the regional haemodynamic effects of CV-11974, which contribute to its hypotensive action, in conscious, chronically instrumented spontaneously hypertensive rats (SHR) and renal hypertensive 2 kidney, 1-clip (2K1C) rats, as well as in appropriate normotensive Wistar Kyoto and sham-operated rats. In SHR, CV-11974 (0.1 mg/kg, i.v.) lowered MAP and increased renal blood flow and conductance, indicating renal vasodilatation. However, there were minimal changes in blood flow in the mesenteric or hindquarters vascular beds. By contrast, in 2K1C rats, CV-11974 caused marked hypotension which was associated with substantial vasodilatation in all three vascular beds. The cardiovascular effects of exogenous AII were also blocked by CV-11974. These results suggest that there are subtle differences in the haemodynamic profile of CV-11974 in the two hypertensive rat models, despite similar resting MAP, since this compound caused a relatively selective renal vasodilatation in SHR, but more widespread vasodilatation in 2K1C rats. PMID- 7889197 TI - Quantitative localization of angiotensin II receptor subtypes in spontaneously hypertensive rats. AB - Angiotensin II (Ang II) receptors were labelled by in vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand in the kidney, adrenal gland, thoracic aorta, and hindbrain of adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Ang II receptors were differentiated into subtypes by susceptibility to subtype 1 (AT1) and subtype 2 (AT2) antagonists. In both rat strains, the adrenal cortex contained predominantly AT1 receptors, while AT2 receptors predominated in the adrenal medulla. The kidney contained exclusively AT1 receptors in glomeruli, proximal tubules, and the outer medulla. AT1 receptors were predominant in the thoracic aorta. The nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus (DM10), area postrema, and spinal trigeminal nucleus (Sp5) contained exclusively AT1 receptors, whereas the nucleus of the inferior olive contained AT2 receptors predominantly. Significant differences in receptor density were observed between SHR and WKY. The adrenal cortex, renal outer medulla, NTS, DM10, and Sp5 displayed higher AT1 receptor density in SHR than in WKY. These results indicate that expression of AT1 receptors is regulated differently in important targets of Ang II in SHR, and suggest that altered regulation of AT1 receptor expression may be relevant to the pathogenesis of hypertension in SHR. PMID- 7889198 TI - Activated angiotensin II generation and regulation in rat mesenteric arteries following nephrectomy. AB - The objectives of the present study were to test the hypothesis that vascular angiotensin II (AII) generation may be negatively regulated by circulating AII in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), and to clarify the role of this vascular AII in the sustained hypertension seen in SHR following nephrectomy. The mesenteric arteries from kidney-intact and nephrectomised WKY and SHR were perfused, and the level of AII released into the perfusate were measured. The effects of CV-11974, a newly developed nonpeptide AII receptor antagonist, on AII release were examined to investigate the existence of a local feedback system in the blood vessels. Nephrectomy augmented vascular AII release both in WKY and SHR despite the reduction in circulating AII. CV-11974 significantly increased AII release from the mesenteric arteries of kidney-intact rats. There were no significant differences in these responses between WKY and SHR. These results suggest that WKY and SHR share a potent pathway for producing vascular AII in response to the withdrawal of circulating AII, although this pathway is not responsible for the sustained hypertension seen in SHR after nephrectomy. PMID- 7889199 TI - Topical application of AT1 receptor antagonists prevents medial and neointimal proliferation after balloon injury. AB - Angiotensin II plays an important role in neointima formation after vascular injury. A rat model of carotid artery injury was used i) to investigate the effect of single topical application of angiotensin II subtype 1 (AT1) receptor antagonists (CV11974, DuP753) in suppressing medial proliferation at day 2 and neointimal proliferation at day 14, and ii) to investigate the antiproliferative effects of additional application of L-arginine (a nitric oxide precursor). Drugs mixed in 25% (W/W) solutions of F127 pluronic gel were applied topically to injured vessels. Early medial proliferation of smooth muscle cells, assessed by the S-bromo-2'-deoxyuridine labelling index, was significantly suppressed by application of CV11974 (5 mg/kg), 7.5% +/- 2.2% vs. 19% +/- 3.9% in the control group. The intima/media ratio following CV11974 (10 mg/kg) or DuP753 (12.5 mg/kg) at day 14 was significantly lower than that in the control group (42% +/- 7%, 43% +/- 14%, and 123% +/- 11%, respectively). Additional application of L-arginine seemed to increase effectiveness, but was not statistically significant. In conclusion, single topical application of AT1 receptor antagonists was effective in suppressing early medial proliferation and neointima formation after balloon injury, suggesting that they may be clinically useful after angioplasty or vascular surgery. PMID- 7889200 TI - Effect of an angiotensin II receptor antagonist, TCV-116, on rat carotid artery neointimal formation after balloon injury. AB - Arterial injury by a balloon catheter produces marked smooth muscle cell proliferation and the participation of angiotensin II in this response has been suggested. In this study, we examined the effect of a novel angiotensin II type I receptor antagonist, TCV-116, on neointimal formation after rat carotid artery balloon injury. Oral administration of TCV-116 at doses of 1, 5 or 10 mg/kg/day significantly reduced the cross-sectional intimal area by 30%, 46% and 54%, respectively, and reduced the ratio of the intimal to medial cross-sectional areas by 23%, 41% and 50%. An angiotensin-converting enzyme inhibitor, lisinopril, had an effect similar to that of TCV-116. The effect of both drugs was significantly correlated with the reduction of both blood pressure and cardiac hypertrophy. We conclude that TCV-116 can prevent neointimal formation after balloon injury as well as reducing blood pressure and preventing cardiac hypertrophy. PMID- 7889202 TI - Is hypertrophy of the walls of pre-glomerular vessels responsible for hypertension in spontaneously hypertensive rats? AB - This paper reviews briefly the experimental support for the hypothesis that hypertrophy of the walls of pre-glomerular vessels may occur in human essential hypertension and in spontaneously hypertensive rats (SHR) and that it may be the primary stimulus to the development of the hypertension. Pre-glomerular hypertrophy with resultant lumen narrowing will simulate narrowing of the main renal artery haemodynamically, as originally proposed by Goldblatt. In SHR there is strong evidence for increased wall thickness of the intra-renal arteries and for structurally based narrowing of the lumen of the afferent arterioles. Compatible with these morphological findings, SHR have increased resting renal vascular resistance and it has been shown experimentally that the extent of increased renal resistance is correlated with the extent of hypertension development. Increased renal vascular resistance occurs early in human essential hypertension too, but direct evidence for pre-glomerular structural changes is lacking and will be difficult to gather. The causes of the pre-glomerular structural changes in SHR remain to be determined, but they do not appear to be secondary to the hypertension. PMID- 7889201 TI - Renal protective effect of TCV-116 in stroke-prone spontaneously hypertensive rats. AB - We examined the effects of TCV-116, a non-peptide selective AT1 receptor antagonist, on cellular phenotype and on the expression of the transforming growth factor-beta 1 (TGF-beta 1) and extracellular matrix genes in the kidneys of stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were given vehicle or TCV-116 (10 mg/kg/day) by gastric gavage for 10 weeks (from the age of 22 to 32 weeks). Renal mRNA levels were measured by Northern blot analysis. In vehicle treated 32-week-old SHRSP, urinary albumin excretion per 24 h was about 26-fold greater than that in age-matched Wistar-Kyoto (WKY) rats, and the mRNA levels of renal TGF-beta 1, fibronectin and collagen types I and III in SHRSP were all several-fold higher than those in WKY. Immunohistochemical studies showed the prominent presence of alpha-smooth muscle actin-expressing glomerular cells in SHRSP, in contrast to their absence in WKY. Treatment of SHRSP with TCV-116 decreased urinary albumin excretion and renal mRNA levels for TGF-beta 1 and for the above-mentioned extracellular matrix components. TCV-116 prevented the phenotypic modulation of glomerular cells in SHRSP. These results suggest that AT1 receptor antagonists may have powerful renal protective effects. PMID- 7889203 TI - Renal protective effects of angiotensin II receptor I antagonist CV-11974 in spontaneously hypertensive stroke-prone rats (SHR-sp). AB - This study was performed to examine the effects of blockade of the renin angiotensin system on the development of hypertension and renal damage in stroke prone spontaneously hypertensive rats (SHR-sp), using a non-peptide angiotensin II receptor antagonist, CV-11974. We examined changes in blood pressure, urinary protein excretion, creatinine clearance and renal morphology in CV-11974-treated SHR-sp rats and compared these variables with those in non-treated SHR-sp and Wistar Kyoto (WKY) rats, as well as in hydralazine-treated SHR-sp rats. CV-11974 lowered systolic blood pressure in a manner similarly to hydralazine (CV-11974 204 +/- 3, hydralazine 200 +/- 3, non-treated SHR-sp 284 +/- 9, WKY 155 +/- 5 mmHg), but reduced urinary protein excretion more than hydralazine (p < 0.01). There were no significant differences in creatinine clearance among experimental groups. The glomerulosclerosis index was greater in non-treated and hydralazine treated SHR-sp rats than in CV-11974 treated SHR-sp and WKY rats (p < 0.01). Hydralazine-treated SHR-sp rats had a lower glomerulosclerosis index than the non treated SHR-sp rats (p < 0.01). No significant differences were found in glomerulosclerosis index between CV-11974-treated SHR-sp and WKY rats. Tubular atrophy, tubular casts and interstitial fibrosis were observed in non-treated SHR sp rats and, occasionally, in hydralazine-treated SHR-sp rats, but not in CV 11974-treated SHR-sp rats or WKY rats. These results indicate that the angiotensin II receptor antagonist was superior to hydralazine as far as renal protection was concerned. This suggests that renal damage in SHR-sp rats is associated not only with hypertension but also with activation of the renin angiotensin system. PMID- 7889204 TI - Nonpeptide angiotensin II type 1 receptor antagonist prevents nephrosclerosis in hypertensive rats. AB - Angiotensin II (AII) appears essential in remnant kidney models of renal injury in rats, and renal injury was reduced by angiotensin-converting enzyme inhibitor (ACEI). To determine whether this is due to AII blockade or other actions of ACEI, we studied a nonpeptide AII type 1 receptor antagonist and an ACEI in partially nephrectomised spontaneously hypertensive rats (SHR). Thirty SHR underwent surgery and were divided into three equal groups: Control, TCV (0.5 mg/kg/day TCV-116), and CAP (30 mg/kg/day captopril). All SHR received a 5%-NaCl diet. Systolic blood pressure (SBP) and urinary protein were measured at 2-week intervals. Serum total protein, albumin, urea nitrogen, and creatinine were determined at week 8. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured at weeks 4 and 8. Renal injury was evaluated histopathologically. TCV and CAP reduced SBP at week 2 and proteinuria at week 8. GFR and RBF fell in all groups, but decreases were not significant in treated SHR and histopathological changes were significantly ameliorated. All blockade by TCV or CAP reduces renal injury in salt-loaded SHR with partial renal ablation. AII is essential in remnant kidney models of renal injury, and AII blockade is essential in renal protection by ACEI. PMID- 7889205 TI - Pharmacological profile of a novel nonpeptide angiotensin II subtype 1 receptor antagonist, TCV-116. AB - TCV-116, an angiotensin II (AII) receptor antagonist, is a prodrug that is converted in vivo to the active form, CV-11974. CV-11974 selectively and competitively inhibited the specific binding of [125I]AII-(Sar1,lle8) to All subtype 1 (AT1) receptors in rabbit aortic membranes (Ki = 0.64 nM) and insurmountably inhibited the AII-induced maximal contractile response of rabbit aortic strips (pD'2 = 9.97). TCV-116 inhibited the AII-induced pressor response in rats (ID50 = 0.069 mg/kg. p.o.). In spontaneously hypertensive rats (SHR), TCV 116 had a sustained antihypertensive effect (ED25 = 0.68 mg/kg, p.o.). Repeated oral administration of TCV-116 (1 mg/kg) to SHR once daily for 2 weeks reduced blood pressure by 30-50 mmHg over 24 h. The antihypertensive effects of TCV-116 correlated well with the inhibition of AII-induced contractile responses of aortic strips prepared ex vivo after administration of TCV-116. TCV-116 had sustained effects in both 2 kidney, 1 clip hypertensive rats and in 1 kidney, 1 clip hypertensive rats, but had no effect in DOCA/salt hypertensive rats. Unlike enalapril, TCV-116 had no potentiating effect on the incidence of cough induced by citric acid in guinea pigs. These results suggest that TCV-116 is a promising antihypertensive agent with once daily administration. PMID- 7889206 TI - Effects of a calcium antagonist and an angiotensin II receptor antagonist on rat renal arterioles. AB - The objective of this study was to investigate the effects of a dihydropyridine calcium antagonist, manidipine HCl, and an angiotensin II receptor antagonist, CV 11974, on renal microvasculature in hypertensive rats. Hydronephrosis was induced by ligation of the left ureter in 8-week-old stroke-prone spontaneously hypertensive rats. Two months after the operation, the hydronephrotic kidney was split longitudinally and spread out as a thin sheet, and the renal microvasculature was observed directly under a light microscope. Administration of manidipine HCl (20 micrograms/kg) caused a gradual fall in blood pressure (-34 mmHg). The afferent arterioles were dilated, and maintained the same level of dilatation until 30 min (+20%). The efferent arterioles were also dilated (+8%). Glomerular blood flow was significantly increased (+38%). Administration of CV 11974 (100 micrograms/kg) caused a sharp fall in blood pressure at 2 min (-24 mmHg), with a continuous fall in blood pressure until 60 min (-46 mmHg). The afferent arterioles were gradually dilated (+15%). The efferent arteriole was also dilated until 60 min, but to a lesser extent than the afferent arteriole. Glomerular blood flow was immediately increased (+35%). We conclude that both manidipine HCl and CV-11974 dilated both the afferent and efferent arterioles and increased glomerular blood flow. PMID- 7889207 TI - Enhancement of hypertension and renal injury by salt-loading during chronic nitric oxide inhibition. Effects of TCV-116, a novel angiotensin II receptor antagonist. AB - Endothelium-derived nitric oxide (EDNO) and angiotensin II play a role in the regulation of vascular tone and sodium handling. The objective of this study was to determine the role played by angiotensin II in mediating the arterial pressure and renal response to increments in sodium intake during chronic EDNO inhibition. Six groups of Wistar rats were studied; they were fed either a normal sodium diet (groups I, II, and III) or a high sodium diet (groups IV, V and VI). Rats in groups II, III, V and VI were placed on oral L-N-nitroarginine-methyl ester (L NAME) for 4 weeks. In groups III and VI, the angiotensin II receptor antagonist, TCV-116, was administered. A significant increase in blood pressure was observed in group V compared with group II at the end of the experimental period. TCV-116 attenuated the L-NAME-induced hypertension in both group III and group VI. Urinary protein excretion and the glomerular sclerotic injury score in group V were greater than in group II. TCV-116 attenuated the proteinuria and glomerular injury induced by chronic EDNO inhibition in the groups with normal (group III) and high sodium intake (group IV). Systemic hypertension and glomerular injury were enhanced by salt loading during EDNO inhibition, and the angiotensin II receptor antagonist, TCV-116, attenuated this salt-induced increase in blood pressure and renal injury, suggesting that EDNO may counteract the renal effects of angiotensin II. PMID- 7889208 TI - Effects of CV-11974 on renal haemodynamics and renal function in dogs. AB - The effects of CV-11974, a nonpeptide angiotensin II (Ang II) receptor antagonist, on renal haemodynamics and function were examined in pentobarbital anaesthetised dogs to evaluate the physiological role of endogenous Ang II in regulating renal haemodynamics and urine formation. Intrarenal infusion of CV 11974 (1 microgram/kg/min) increased renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, and urinary electrolyte excretion (Na and K), with no change in mean arterial pressure (MAP). In another group of dogs, intrarenal infusion of CV-11974 (1 microgram/kg/min) increased the fractional excretion of sodium, the fractional proximal excretion of sodium, and the fractional distal excretion of sodium. CV-11974 did not affect the linear relationship between the free water reabsorption rate (TCH2O) and osmolar clearance (Cosm). These results suggest that endogenous Ang II may play an important role in regulating renal haemodynamics and stimulating sodium reabsorption. Our data indicates that endogenous Ang II may stimulate sodium reabsorption at the proximal and the distal portions of the tubule, with the exception of the medullary portion of the ascending limb of Henle. PMID- 7889209 TI - Effect of an AT1 receptor antagonist (CV-11974) on angiotensin II-induced cardiomyocyte hypertrophy in vitro. AB - Angiotensin (ANG) II, a potent vasoconstrictor is known to be a hypertrophic factor for cardiomyocytes. Recently, endothelin (ET)-1 has also been shown to be an autocrine/paracrine growth factor for cardiomyocytes. To determine the cellular mechanism by which ANG II induces cardiac hypertrophy, we studied the effects of ANG II on the gene expression of ET-1 and ET receptor subtypes (ETA, ETB), as well as its effects on the expression of immediate early oncogenes (c fos, c-myc) in cultured rat cardiomyocytes in vitro. ANG II (10(-7) M) increased steady-state mRNA levels of ET-1 in the same manner as c-fos and c-myc during a short incubation period (0.5-1 h), while ANG II induced ETB receptor mRNA, but not ETA receptor mRNA, during a long incubation period (6-12 h). CV-11974, an antagonist of ANG II receptor type-1 (AT1), inhibited the ANG II-induced expression of c-fos, c-myc and ET-1 mRNAs, as well as that of ETB receptor mRNA, whereas PD-123319, an antagonist of the ANG II type-2 (AT2) receptor, failed to block such induction. CV-11974 similarly blocked ANG II-induced immediate-early oncogenes (c-fos, c-myc) in cultured rat vascular smooth muscle cells. Our findings indicate that ANG II immediately upregulates the cardiac ET-1 gene in the same manner as it does the immediate early protooncogenes, while the late induction of the ETB receptor, mainly via the cardiac AT1 receptor, suggests the involvement of endogenous ET-1 in ANG II-induced cardiac hypertrophy. PMID- 7889211 TI - Effect of an angiotensin II receptor antagonist, TCV-116, on cardiac hypertrophy and coronary circulation in spontaneously hypertensive rats. AB - To determine whether an angiotensin II receptor antagonist (AT antagonist) could improve the impaired coronary circulation as well as induce regression of cardiac hypertrophy in the hypertensive heart, and to elucidate whether the nitric oxide system in the coronary artery was involved in this mechanism, the AT1 antagonist, TCV-116 (10 mg/kg), was administered orally to spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY), and coronary flow was measured in the isolated hearts. High systolic blood pressure in SHR was significantly reduced by a 2-week treatment with TCV. Left ventricular (LV) hypertrophy in SHR regressed after TCV treatment, while LV weight in WKY was not reduced. Total minimum coronary vascular resistance (MCVR) obtained with adenosine (10(-5) M) infusions in a Langendorff apparatus was significantly greater in SHR than in WKY. Increased MCVR in SHR was reduced after TCV treatment. Coronary perfusion with NG monomethyl-L-arginine monoacetate (L-NMMA) increased coronary vascular resistance (CVR) in WKY, while it failed to increase CVR in SHR. TCV treatment restored the responses to L-NMMA in SHR. These findings suggest that the AT1 antagonist, TCV 116, lowered the high blood pressure in SHR, concomitantly improving the impaired coronary circulation, and that it induced regression of the cardiac hypertrophy. The suppressed nitric oxide (NO) system in the coronary vessels in SHR appeared to be activated by TCV treatment. PMID- 7889210 TI - Angiotensin II receptor antagonist, TCV-116, prevents myocardial hypertrophy in spontaneously hypertensive rats. AB - Recently, it has been suggested that angiotensin II (AII) might be associated with cardiac hypertrophy and fibrosis. We investigated the preventive effect of an AII receptor antagonist, TCV-116, on the development of cardiac hypertrophy and fibrosis in spontaneously hypertensive rats (SHR) at 24 weeks of age through histopathological study and an AII receptor assay. Treatment with TCV-116, enalapril (an angiotensin-converting enzyme inhibitor, ACEI), and hydralazine for 20 weeks lowered systolic blood pressure (SBP) significantly (-39 mmHg, -45 mmHg, and -45 mmHg, respectively). The heart weight/body weight ratio, cardiac myocyte diameter, and percent cardiac fibrosis were significantly reduced by treatment with TCV-116 and enalapril as compared with hydralazine treatment or no treatment. The AII receptor density was significantly increased by treatment with TCV-116 and enalapril as compared with hydralazine treatment or no treatment. The results of this study suggest that AII receptors are involved in the development of cardiac hypertrophy and fibrosis in SHR. It was demonstrated that the AII receptor antagonist, TCV-116, was comparable to the ACEI, enalapril, in inhibiting the progression of cardiac hypertrophy and fibrosis via the AII receptor. PMID- 7889212 TI - Comparative effects of an angiotensin-converting enzyme inhibitor and an angiotensin II antagonist in Dahl rats. AB - The antihypertensive, cardioprotective, and renoprotective effects of a nonpeptide angiotensin II antagonist (AIIA, CV-11974) and an angiotensin converting enzyme inhibitor (CEI, captopril) were compared in Dahl salt-sensitive rats. Six-week-old male rats received a high-salt diet (4% NaCl) and were divided into control, CEI, and AIIA groups. The CEI group received captopril (15 mg/kg/day) and the AIIA group received CV-11974 (0.72 mg/kg/day), an active metabolite of the AIIA TCV-116, for 4 weeks by continuous subcutaneous infusion. After 4 weeks, systolic blood pressure (SBP) was significantly lower in the treatment groups than in the control group. The heart weight/body weight ratio and urinary protein excretion were reduced in the treatment groups, and renal damage (glomerular sclerosis score) was reduced by approximately 50%. CV-11974 and captopril were comparable in reducing BP, cardiac hypertrophy, and renal damage, suggesting that the renin-angiotensin (R-A) system is involved in elevating BP and promoting cardiovascular damage, despite suppression of the R-A system in this model. The antihypertensive effect of CEI may be due primarily to inhibition of the action of angiotensin II, while other effects, e.g., potentiation of the kinin system, may be less important. PMID- 7889213 TI - Nerve growth factor and Alzheimer's disease. AB - Nerve growth factor (NGF) is a well-characterized protein that exerts pharmacological effects on a group of cholinergic neurons known to atrophy in Alzheimer's disease (AD). Considerable evidence from animal studies suggests that NGF may be useful in reversing, halting, or at least slowing the progression of AD-related cholinergic basal forebrain atrophy, perhaps even attenuating the cognitive deficit associated with the disorder. However, many questions remain concerning the role of NGF in AD. Levels of the low-affinity receptor for NGF appear to be at least stable in AD basal forebrain, and the recent finding of AD related increases in cortical NGF brings into question whether endogenous NGF levels are related to the observed cholinergic atrophy and whether additional NGF will be useful in treating this disorder. Evidence regarding the localization of NGF within the central nervous system and its presumed role in maintaining basal forebrain cholinergic neurons is summarized, followed by a synopsis of the relevant aspects of AD neuropathology. The available data regarding levels of NGF and its receptor in the AD brain, as well as potential roles for NGF in the pathogenesis and treatment of AD, are also reviewed. NGF and its low affinity receptor are abundantly present within the AD brain, although this does not rule out an NGF-related mechanism in the degeneration of basal forebrain neurons, nor does it eliminate the possibility that exogenous NGF may be successfully used to treat AD. Further studies of the degree and distribution of NGF within the human brain in normal aging and in AD, and of the possible relationship between target NGF levels and the status of basal forebrain neurons in vivo, are necessary before engaging in clinical trials. PMID- 7889214 TI - Peripheral markers and diagnostic criteria in Alzheimer's disease: critical evaluations. AB - This review analyzes recent developments in diagnostic criteria and peripheral markers used clinically in the definitive diagnosis of Alzheimer's disease (AD), comparing past and current views, together with a discussion of their shortcoming and difficulties of implementation. Consideration is given to studies on the presence of amyloid substances outside the central nervous system: in cerebrospinal fluid, in plasma, in primary cultures, and in continuous cultures of cell lines of neuronal and glial origin. We discuss alterations of cholinesterases and noradrenaline in red blood cells (RBC) in AD and, with relation to the infectious theory, the presence of spirochaetes in patients. The activities of the enzymes leading to the formation of amyloid substances and those reflecting more general alterations of metabolic processes are considered, both in respect to their role in the pathogenesis of the neurodegenerative disorders of AD and of their potential use as markers. Enzymatic changes have been studied comparing AD patients with non AD controls as well as with AD relatives: proteases and their inhibitors; plasminogen activators; transketolases; increases in the activity of Cu-Zn superoxide dismutase in AD patients' RBC, serum, fibroblasts and cortical neurons, pointing to alterations in oxidative processes; and apolipoprotein E epsilon 4 allele, linked to late onset AD and familial cases. This review presents reasons why the involvement of peripheral markers in AD should advance from hypothesis to accepted fact. PMID- 7889216 TI - Cerebellar and brainstem circuits involved in classical eyeblink conditioning. AB - Model systems are one useful strategy for the investigation of the mechanisms of learning. Whereas mammalian model systems generally do not offer the ease of identifying circuitry and exploring cellular mechanisms of learning that is realized with invertebrate preparations /37,97/, research involving the rabbit classical eyeblink conditioning paradigm has now reached the state at which much of the basic conditioning neural circuit appears to have been identified /9,65,66,85,89,91/. Despite a dispute as to precisely where in the circuitry convergence of the associated stimuli may occur, there is substantial evidence identifying the stimulus input pathways and motor output pathway. The present summary of this research details these paths. In addition, the proposed sites of convergence of the conditioning stimuli are discussed. Finally, a hypothesized neural circuit responsible for classical eyeblink conditioning is presented along with some suggestions for future research directions. PMID- 7889215 TI - Analysis of connectivity: neural systems in the cerebral cortex. AB - The mammalian cerebral cortex is composed of many distinct areas, which are very richly interconnected. The very large number of connections between cortical areas require analysis to be undertaken before reliable conclusions about the organization of neural systems in the cortex can be drawn. We review the methodology and results of two means of analysing central nervous connectivity, hierarchical analysis and optimization analysis. We conclude that these methods are reliable methods for analysing neural connectivity data, and that their results concur. The analyses indicate that all major cortical sensory systems are organized hierarchically, some central sensory systems are divided structurally into several "streams" of processing, the cortical motor system is embedded in the cortical somatosensory system, the frontal and limbic structures are connectionally associated, and that these frontal and limbic areas are invariably associated with the least peripheral sensory processing regions, and are therefore connectionally central. Finally, we discuss the differences on this common plan between the organizations of the cat and primate that these analyses reveal. PMID- 7889217 TI - The significance of three-field lymphadenectomy in oesophageal cancer surgery. PMID- 7889218 TI - Tumor necrosis factor and cachexia: a current perspective. AB - Anorexia, net proteolysis of skeletal muscle and consumption of body fat are hallmarks of the cachexia syndrome associated with chronic disease states. While inanition contributes to cachexia, this wasting diathesis has little in common with simple starvation. The cachexia syndrome is characterized by progressive weight loss and depletion of lean body mass in excess to that resulting from comparable caloric restriction. Accelerated mobilization and consumption of host protein stores from peripheral tissues occurs to support gluconeogenesis and acute phase protein synthesis [1, 2]. In contrast, simple starvation is associated with a relative sparing of lean tissue with the preferential consumption of fat. While the clinical manifestations of cachexia are readily apparent, identification of the specific mechanisms responsible for the development of cachexia remains an enigma. In recent years, interest has focused on the role that the immune system plays in the development of cachexia. Investigators initially hypothesized that the chronic production of two inflammatory cytokines, tumour necrosis factor alpha (TNF alpha) and/or interleukin-1 (IL-1), could explain the host non-specific responses resulting in cachexia [3-5]. Other pro-inflammatory cytokines, including interleukin-6 (IL-6) [6, 7] and interferon-gamma [8, 9], have been more recently proposed to be involved in this complex process. Although no consensus exists for the exclusive role of any one cytokine in the pathogenesis of cachexia, there is growing acceptance that the progression of cachexia results in part from the inappropriate release of one or more pro-inflammatory cytokines [10, 11]. In the present review, the current role of TNF alpha as a mediator of cachexia is examined. PMID- 7889219 TI - An evaluation of five different methods for estimating proliferation in human colorectal adenocarcinomas. AB - Five different methods of determining cell proliferation have been compared in samples taken from a group of 125 human colorectal tumours labelled in vivo with iododeoxy-uridine (IUdR). The labelling index (LI) was obtained immunocytochemically using monoclonal antibodies against proliferating cell nuclear antigen (PCNA), the Ki67 antigen and IUdR (IUdRimm). Incorporation of IUdR was also determined flow cytometrically (IUdRfcm) and PCNA expression was measured in both formalin- and methanol-fixed tissue (PCNAf and PCNAm respectively). There was significant variation in the results obtained both within and between the different assays. Paired analysis of the data showed that the correlation between the different methods of determining the LI was poor. However, the IUdRfcm LI was significantly correlated with both IUdRimm (r = 0.39; n = 78; P < 0.001 by Spearman's test) and Ki67 LIs (r = 0.32; n = 87; P < 0.001). The IUdRimm LI was also significantly related to the Ki67 LI (r = 0.44; n = 60; P < 0.001). The median IUdRfcm and IUdRimm LIs were significantly higher in the aneuploid vs. the diploid tumours (17.4% vs. 6.2% for IUdRfcm; 23.2% vs. 18.9 for the IUdRimm; P < 0.001 and P = 0.014 respectively by Mann-Whitney U-test) but none of the other proliferative indices showed this relationship. Finally, none of the LIs showed a significant association with the clinical characteristics of the tumours such as stage, grade, age, sex or fixity. The findings of this investigation highlight the need for carefully controlled studies when assessing the value of proliferation markers in solid human tumours. PMID- 7889220 TI - The influence of fibroblasts on the growth of human colorectal carcinoma xenografts. AB - Colorectal carcinoma xenografts were grown in nude mice by inoculation with and without fibroblasts. A significantly greater proportion of tumours grew in mice receiving carcinoma cells with fibroblasts (83% compared to 52%). Tumour weight and thymidine DNA labelling were not significantly different. Initial development but not subsequent growth of xenografts was enhanced by fibroblasts. PMID- 7889221 TI - The bispecific antibody 500A2 x 96.5 targets T-lymphocytes activated in vivo with staphylococcal enterotoxin B (SEB) against CL62 melanoma cells in vitro. AB - Bispecific antibodies (BAb) direct T-lymphocytes to lyse selected tumour targets, both in vitro and in vivo. Significant tumour cell lysis with BAb requires pre expansion of T-lymphocytes, which may be achieved in vitro by the addition of anti-CD3 monoclonal antibody plus interleukin-2 (IL-2), but anti-CD3 may cause immunosuppression. We investigated an alternative agent for in vivo immunostimulation, staphyloccal enterotoxin B (SEB), which selectively activates certain T-cell subsets and may result in less immunosuppression than with anti CD3. We activated T-lymphocytes in vivo with SEB, expanded them in vitro with IL 2, and directed them against a tumour target with the BAb 500A2 x 96.5, specific for the murine CD3 antigen and the melanoma p97 antigen expressed by the CL62 tumour. C3H mice received SEB 50 micrograms intraperitoneally (i.p.). After 18 h mice were sacrificed and splenocytes extracted and either passed over a nylon wool column to isolate T-lymphocytes, or cultured in vitro for 3 to 7 days with 100 U ml-1 of IL-2. A 4-h chromium-release assay was used to assess the ability of T-lymphocytes to lyse the tumour target CL 62 in the presence or absence of the bispecific antibody 500A2 x 96.5. The addition of BAb significantly enhanced tumour lysis by SEB activated cells after a period of in vitro culture with IL-2. In vivo SEB results in the activation of T-lymphocytes which may be directed by bispecific antibodies to increase the lysis of selected tumour targets in vitro. PMID- 7889222 TI - Antitumour activity of 5-fluorouracil, verapamil and hyperthermia against human gastric adenocarcinoma cell (AGS) in vitro. AB - The purpose of this study was to assess the efficacy of verapamil (20 microM) and hyperthermia (42 degrees C) as modifiers of 5-fluorouracil (5-FU), used at different concentrations, in inhibiting the growth of gastric adenocarcinoma cells. Combined verapamil and hyperthermia treatment showed a significant decrease in cell count when compared to control (72.2%), hyperthermia alone (68.4%), or verapamil alone (65%). At a high concentration of 5-FU (50 micrograms/ml), verapamil and hyperthermia had an additive growth inhibitory effect over a 4-day period when compared to control. A combination of 5-FU at low concentration (0.5 microgram/ml) with verapamil significantly suppressed growth by 31.2% in comparison to control--with this effect being independent of the duration of treatment. The modalities analysed in this study require further investigation and have potential for clinical applicability to gastric cancer therapy in the future. PMID- 7889223 TI - Ectopic breast cancer: case report and literature review. AB - Ectopic breast tissue includes both supernumerary and aberrant breast tissue. The incidence of supernumerary tissue has been reported as high as 6% depending on the ethnic group studied. The incidence of aberrant breast tissue remains unknown. The development of malignancy within these anomalies is rare. In the following paper, the case report of a patient with an ectopic breast cancer and a second primary cancer of the left anatomic breast is described. A review of the world literature on ectopic breast cancer follows. Specific characteristics of ectopic breast cancer are defined and recommendations for management are made. PMID- 7889224 TI - Screening mammography: interpretation of the data. AB - The literature on screening mammography includes a plethora of conflicting articles. More recently, individuals and various medical organizations have recommended and established their own guidelines for screening mammography. A review of salient breast screening randomized clinical trials in women over and under the age of 50 years is provided and compared with the more recent results of the Canadian National Breast Screening Study. In women under the age of 50 years, screening mammography cannot be supported from the results of these trials. In women over the age of 50 years, screening mammography leads to a significant reduction in breast cancer mortality and should be strongly recommended. PMID- 7889225 TI - The AB/BA crossover: past, present and future? AB - The AB/BA design is reviewed from a historical perspective. Particular attention is paid to the problem of carry-over and various attempts to deal with it. The two-stage procedure, an approach which was popular for many years, is shown to be unsafe. The analysis of AB/BA designs with baseline data is also considered. It is shown that such baselines do not provide a cure for the problem of carry-over; and it is concluded that any rational analysis of such trials will always be dependent on assumptions regarding carry-over, and that it is necessary to pay particular attention to washout periods. Under such circumstances analysis of covariance may be useful. In conclusion, some speculative comments about future lines of research are offered. PMID- 7889226 TI - The analysis of binary and categorical data from crossover trials. AB - A review is presented of methods for the analysis of discrete data from crossover trials. The definition and interpretation of the model for the data is used as a central theme. Distinctions are drawn between different types of model, particularly marginal and subject specific. It is seen how much recent methodology for analysing correlated categorical data can be applied successfully to the crossover setting. The current accessibility of each method is considered and the different approaches are illustrated and compared using two examples. PMID- 7889227 TI - Review of nonparametric methods for the analysis of crossover studies. AB - This paper reviews nonparametric methods for the analysis of crossover studies. Primary attention is given to crossover studies to compare two treatments for a response variable that has a metric measurement level. For this situation, one can often test hypotheses or obtain confidence intervals for parameters of interest by applying well known univariate nonparametric rank methods (e.g., the Wilcoxon rank sum test, or the Wilcoxon signed rank test) to appropriately specified functions of the data. Related extensions are also available, to some degree, for crossover studies to compare more than two treatments or those for which the measurement level of the response variable is ordinal or has a censored time-to-event nature. Methods for several specific situations along these lines are discussed in terms of principles with potentially broader applicability. Several examples are provided to illustrate the performance of some of the methods. PMID- 7889228 TI - Multi-period crossover trials. AB - This paper presents a review of crossover designs for use in medical applications which have three or more treatment periods. Only outcomes which can be analysed as continuous variables are considered. Designs which purport to allow for carryover effects are reviewed in detail, as are methods for analysing data collected in such trials. In practice, it is often possible to eliminate carryover by interposing sufficiently long 'washout' periods between successive treatments, and suitable designs for this case are also mentioned. Much current practice revolves around a model which has been widely criticized: the shortcomings of this model and the implications of possible remedies, for design as well as analysis, are discussed. PMID- 7889229 TI - Bayesian analyses of two-treatment crossover studies. AB - This review covers Bayesian analyses of two-treatment crossover studies. The main emphasis is placed on the analysis of continuous data although we also consider dichotomous responses. Studies discussed include (1) the simple two-period, two treatment crossover, (2) the two-period crossover with one baseline measurement, (3) the two-period crossover with two baselines and (4) the extra-period design with two treatment sequences. PMID- 7889230 TI - Heart rate and heart rate variability in normal young adults. AB - INTRODUCTION: The relationships between heart rate (HR) and HR variability (HRV) are not simple. Because both depend on the autonomic nervous system (ANS), they are not independent variables. Technically, the quantification of HRV is influenced by the duration of the cardiac cycles. The complexity of these relationships does not justify ignoring HR when studying HRV, as frequently occurs. METHODS AND RESULTS: Using spectral and nonspectral methods, the HR and various normalized and non-normalized indices of HRV were studied in 24-hour recordings of a homogeneous cohort of seventeen 20-year-old healthy males. The HR HRV relationships were appraised by analyzing the same data in two different ways. The 24 mean hourly values provide consistent information on the circadian behavior of the indices, while the average 24-hour individual data show a wide spectrum of normality. Combined approaches allow assessment of the direct impact of RR interval on HRV evaluation. The correlations between HR and normalized indices of HRV are weaker in 24-hour individual data than in pooled hourly data of the same individuals. These correlations are close to 1 in the latter case, which does not mean that measuring HRV is simply another method of evaluating HR, but that normal physiology supposes a harmonious behavior of the various indices. When considered individually without normalization, the specific indices of vagal modulation (high-frequency band of the spectrum, short-term HR oscillations of the nonspectral analysis) consistently increase at night and diminish during the day. However, the low-frequency power, which supposedly reflects sympathetic influences, also increases at night, whereas more logically the longer HR oscillations would predominate during the day. Moreover, the selective analysis of HR oscillations during HR acceleration or decrease indicates that their behavior differs accordingly. CONCLUSION: We recommend that closer attention be paid to the complex relationships between HR and HRV. The strong correlations found in healthy subjects may reflect either the physiological harmony of ANS functions or simple redundancy. Their tendency to deteriorate in diseased hearts suggests that redundancy is not the cause and that abnormalities of ANS functions are not demonstrated by HRV analysis alone. PMID- 7889231 TI - Transvenous-subcutaneous defibrillation leads: effect of transvenous electrode polarity on defibrillation threshold. AB - INTRODUCTION: The defibrillation threshold (DFT) of a transvenous-subcutaneous electrode configuration is sometimes unacceptably high. To obtain a DFT with a sufficient safety margin, the defibrillation field can be modified by repositioning the electrodes or more easily by a change of electrode polarity. In a prospective randomized cross-over study, the effect of transvenous electrode polarity on DFT was evaluated. METHODS AND RESULTS: In 21 patients receiving transvenous-subcutaneous defibrillation leads, the DFT was determined intraoperatively for two electrode configurations. Two monophasic defibrillation pulses were delivered in sequential mode between either the right ventricular (RV) electrode as common cathode and the superior vena cava (SVC) and subcutaneous electrodes as anodes (configuration I) or the SVC electrode as common cathode and the RV and subcutaneous electrodes as anodes (configuration II). In each patient, both electrode configurations were used alternately with declining energies (25, 15, 10, 5, 2 J) until failure of defibrillation occurred. The DFT did not differ between both configurations (18.3 +/- 8.2 J vs 18.9 +/- 8.9 J; P = 0.72). Eleven patients had the same DFT with both electrode configurations, 5 patients a lower DFT with the RV electrode as cathode, and 5 patients a lower DFT with the SVC as cathode. Four patients had a sufficiently low DFT (< or = 25 J) with only 1 of the 2 configurations. CONCLUSION: A change of electrode polarity of transvenous-subcutaneous defibrillation electrodes may result in effective defibrillation if the first electrode polarity tested fails to defibrillate. In general, neither the RV electrode nor the SVC electrode is superior if used as a common cathode in combination with a subcutaneous anodal chest patch. PMID- 7889232 TI - The influence of myocardial systolic shortening on action potential duration following changes in left ventricular end-diastolic pressure. AB - INTRODUCTION: Contraction-excitation feedback may be an important factor in arrhythmogenesis in patients with heart failure. We have previously demonstrated the contrasting effects of raising left ventricular end-diastolic pressure on action potential duration in dog and guinea pig hearts. The current study was undertaken to assess whether these differing effects might reflect differences in the effect of varying left ventricular end-diastolic pressure on systolic shortening in the two models. METHODS AND RESULTS: Two models were studied and compared. In open chest dog hearts and isolated guinea pig hearts, measurements of myocardial segment length were made while left ventricular end-diastolic pressure was raised and lowered at constant left ventricular peak systolic pressure. Action potentials were also recorded while left ventricular end diastolic pressure was changed. The dog hearts were studied further in a manner aimed at reproducing the contraction pattern of the guinea pig hearts. In the in situ dog heart, elevation of left ventricular end-diastolic pressure, and the consequent increase in end-diastolic segment length, was accompanied by a marked increase in systolic shortening, such that minimum systolic segment length remained unchanged. Elevation of left ventricular end-diastolic pressure was accompanied by a prolongation of action potential duration. In the in vitro guinea pig model, elevation of left ventricular end-diastolic pressure was accompanied by more modest changes in systolic shortening, which were not sufficient to compensate for increased diastolic segment length. Consequently, minimum systolic segment length increased as the hearts dilated. Elevation of left ventricular end-diastolic pressure was accompanied by a shortening of action potential duration. In a further series of experiments, the effects of increased left ventricular end-diastolic pressure were studied in the dog model while allowing aortic pressure to rise, thereby restricting systolic shortening. Under these circumstances, the dog model was similar to the guinea pig model, with an increase in left ventricular end-diastolic pressure causing a shortening of action potential duration. CONCLUSION: Our results suggest that the effects of preload changes on action potential duration depend on accompanying changes in systolic shortening. This suggests a possible role for contraction-excitation feedback in arrhythmogenesis in patients with regional wall-motion abnormalities. PMID- 7889233 TI - Role of Na+:Ca2+ exchange current in Cs(+)-induced early afterdepolarizations in Purkinje fibers. AB - INTRODUCTION: The ionic mechanisms for early afterdepolarizations (EADs) have not been fully clarified. It has been suggested that L-type Ca2+ current (ICaL) is the primary current generating EADs that occur near the plateau level (E-EADs) of the membrane potential (Vm) when ICaL is enhanced. The purpose of these studies was to determine accurately the range of Vm at which EADs occur in Purkinje fibers with K+ currents blocked by Cs+ and to investigate the importance of Na+:Ca2+ exchange current (INa:Ca) as opposed to ICaL and other currents in the generation of EADs occurring later during repolarization (L-EADs). METHODS AND RESULTS: Shortened Purkinje strands from dogs and guinea pigs were superfused with physiologic solution containing Cs+ (3.6 mM) and a low [K+]o (3.0 or 2.0 mM) to induce EADs. The Vm of origin of EADs and their evolution were measured with the aid of phase plane plots of the rate of repolarization against Vm. L-EADs occurred over a wide range of Vm (-35 to -90 mV), generally more negative in guinea pig than in dog. Elevation of [Ca2+]o from 1.8 to 3.6 mM suppressed L-EADs within a few cycles, and they returned with continued exposure. After repeated exposures to high [Ca2+]o, L-EADs migrated toward less negative Vm when [Ca2+]o was reestablished to 1.8 mM in the presence of Cs+. Reduction of [Na+]o from 147.5 to 112.5 mM by substitution with Li+ or sucrose also rapidly depressed L EADs. CONCLUSIONS: The observation of Cs(+)-induced L-EADs over a wide range of Vm indicates that there is not a single inward gated current as a common ionic mechanism for L-EADs but does not exclude an important role for INa:Ca, which can operate over a wide range of Vm. The rapid suppression of L-EADs with elevated [Ca2+]o and reduced [Na+]o and the migration of EADs to more positive Vm after exposures to high [Ca2+]o are compatible with INa:Ca as the major charge carrier for L-EADs. PMID- 7889234 TI - Electrotonic inhibition and active facilitation of excitability in ventricular muscle. AB - INTRODUCTION: The effects of subthreshold electrical pulses on the response to subsequent stimulation have been described previously in experimental animal studies as well as in the human heart. In addition, previous studies in cardiac Purkinje fibers have shown that diastolic excitability may decrease after activity (active inhibition) and, to a lesser extent, following subthreshold responses (electrotonic inhibition). However, such dynamic changes in excitability have not been explored in isolated ventricular muscle, and it is uncertain whether similar phenomena may play any role in the activation patterns associated with propagation abnormalities in the myocardium. METHODS AND RESULTS: Experiments were performed in isolated sheep Purkinje fibers and papillary muscles, and in enzymatically dissociated guinea pig ventricular myocytes. In all types of preparations introduction of a conditioning subthreshold pulse between two suprathreshold pulses was followed by a transient decay in excitability (electrotonic inhibition). The degree of inhibition was directly related to the amplitude and duration of the conditioning pulse and inversely related to the postconditioning interval. Yet, inhibition could be demonstrated long after (> 1 sec) the end of the conditioning pulse. Electronic inhibition was found at all diastolic intervals and did not depend on the presence of a previous action potential. In Purkinje fibers, conditioning action potentials led to active inhibition of subsequent responses. In contrast, in muscle cells, such action potentials had a facilitating effect (active facilitation). Electrotonic inhibition and active facilitation were observed in both sheep ventricular muscle and guinea pig ventricular myocytes. Accordingly, during repetitive stimulation with pulses of barely threshold intensity, we observed: (1) bistability (i.e., with the same stimulating parameters, stimulus:response patterns were either 1:1 or 1:0, depending on previous history), and (2) abrupt transitions between 1:1 and 1:0 (absence of intermediate Wenckebach-like patterns). Simulations utilizing an ionic model of cardiac myocytes support the hypothesis that electrotonic inhibition in well-polarized ventricular muscle is the result of partial activation of IK following subthreshold pulses. On the other hand, active facilitation may be the result of an activity-induced decrease in the conductance of IK1. CONCLUSION: Diastolic excitability of well-polarized ventricular myocardium may be transiently depressed following local responses and transiently enhanced following action potentials. On the other hand, diastolic excitability decreases during quiescence. Active facilitation and electrotonic inhibition may have an important role in determining the dynamics of excitation of the myocardium in the presence of propagation abnormalities. PMID- 7889235 TI - Implantable cardioverter defibrillator patch erosion presenting as hemoptysis. AB - Although the internal cardioverter defibrillator has prevented many premature deaths from lethal ventricular arrhythmias, some complications have occurred with its use. We present a patient who developed a fistula between the left ventricle and a bronchus, caused by erosion of the ventricular patch. The patient's presenting symptom was hemoptysis. Physicians caring for patients with these devices should be aware of this potential problem. PMID- 7889236 TI - Flecainide. AB - Flecainide is a Class IC antiarrhythmic agent whose primary electrophysiologic effect is a slowing of conduction in a wide range of cardiac tissues. It is well absorbed and effective in suppressing isolated premature ventricular contractions (PVCs) or nonsustained ventricular arrhythmia but has only a modest efficacy when electrophysiologic testing is used as an endpoint. Its adverse effect on mortality in the CAST trial suggested a propensity to proarrhythmia--a phenomenon to which the Class IC agents appear particularly prone. Despite the applicability of the CAST study only to patients with a prior myocardial infarction, there has been a shift away from flecainide in ventricular arrhythmia, but the low noncardiac side effect profile of the agent allows for its continued use in a wide variety of supraventricular arrhythmias. PMID- 7889237 TI - Is there any indication for an intracardiac defibrillator for the treatment of atrial fibrillation? AB - The experience gained using intracardiac cardioverter defibrillators for the treatment of ventricular arrhythmias has prompted the development of an automatic atrial defibrillator capable of detecting and automatically terminating atrial fibrillation (AF). Experimental studies in sheep have shown that it is possible to terminate AF with energies ranging from < 1 to 7 joules [J], using biphasic shocks. The best electrode configuration using intracardiac catheters and/or a subcutaneous patch was two catheters, one in the right atrium and the other in the coronary sinus. Current studies in man focus on the answers to three questions. First, can the experimental results of atrial defibrillation derived from healthy anesthetized sheep without spontaneous AF be extrapolated to AF in man with areas of fibrosis within the atria and/or underlying heart disease in 80% of cases? Preliminary studies in man suggest that cardioversion of AF of short duration is feasible using a mean energy of 2 J. Second, are these energies well tolerated in an awake nonsedated patient? Energies < 1 J were well tolerated, but pain resulting from higher energies needs further investigation. Third, is low-energy atrial defibrillation safe, i.e., is there a risk of ventricular arrhythmias induced by an atrial shock? Experimental results in sheep have shown that the risk of R wave synchronized shock to induce ventricular arrhythmias was only present when the preceding RR interval was shorter than 300 msec. The risk of proarrhythmia in man is undergoing evaluation and must be sufficiently low (< 0.1) before sanctioning implantation of a stand-alone (without associated ventricular defibrillator) automatic atrial defibrillator. Preliminary data on 1212 shocks showed no proarrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889239 TI - [Homeopathy; a therapeutic practice for the mobilization of self-healing powers]. PMID- 7889238 TI - Efficacy and safety of different aspirin dosages on vascular diseases in high risk patients. A metaregression analysis. AB - PURPOSE: To compare the efficacy and safety of different aspirin dosages in trials with patients at increased risk of vascular disease. DATA SOURCES: Pertinent studies were selected using MEDLINE (1966 through 1992), weekly reviews of Current Contents (1970 through 1992), and references from review articles and editorials. STUDY SELECTION: Thirty-six randomized control trials of aspirin compared with another dosage of aspirin or with placebo. METHODS: The Mantel Haenszel method of pooling odds ratios and metaregression involving log odds ratio (and the risk difference) on aspirin dosage, adjusting for the control rate and the mean length of follow up of the studies. RESULTS: For all patients and for subgroups of patients with previous vascular conditions, there was no relationship between dose and vascular events. For all patients, a dose-response relation was not found with gastrointestinal hemorrhages and hemorrhagic stroke, but was found with gastrointestinal symptoms and withdrawals from side effects. For every 25 mg/day increase in aspirin dosage, the odds ratio of gastrointestinal symptoms and withdrawals increased, respectively, by 0.87% (99% Cl, 0.18 to 1.57%) and 0.94% (99% Cl, 0.06 to 1.82%). The corresponding absolute risk increases were 0.58 and 0.78 per 1,000 patients. CONCLUSIONS: Direct and indirect comparisons of high-risk patients suggest no statistical differences in efficacy, gastrointestinal bleeds, and hemorrhagic strokes across aspirin dosages. These comparisons, however, suggest decreased risk of gastrointestinal symptoms and of withdrawals with lower doses of aspirin. More direct comparison studies are warranted that should contrast the benefits and risks to determine the net benefit. PMID- 7889240 TI - [Attempt at classifying therapeutic processes]. PMID- 7889242 TI - [Bandages and compresses. Their external use in constipation and sleep disorders]. PMID- 7889241 TI - [Taking note--moving--encountering]. PMID- 7889243 TI - [Cottage cheese compresses. An alternative method in superficial phlebitis]. PMID- 7889244 TI - [Nursing standards. An aid to quality assurance. 1]. PMID- 7889245 TI - [Ambulatory surgery. Possibilities and limitations]. PMID- 7889246 TI - [Hygieia, the goddess of health]. PMID- 7889247 TI - [Nursing in disaster areas. A critical report]. PMID- 7889248 TI - [Accident during a work-related trip]. PMID- 7889249 TI - [Critique of "Pflege aktuell"]. PMID- 7889251 TI - Malpractice implications of pressure ulcers. AB - This article explores the legal ramifications flowing from the negligent treatment of pressure ulcers. A review of litigated cases provides examples of how American courts deal with this complex condition. References that may be used to reduce vulnerability to malpractice claims are provided. PMID- 7889250 TI - Histopathology of pressure ulcers as a result of sequential computer-controlled pressure sessions in a fuzzy rat model. AB - This study describes the sequential histopathological changes that occur in the development of pressure ulcers experimentally induced in the fuzzy rat model. Computer-controlled pressure was applied for six hours at a maximum of five sessions, to skin over the greater trochanter of anesthetized rats. Lesions were similar, but more pronounced after the third, fourth, and fifth sessions as compared to the first or second sessions. Lesions developed first in the muscle rather than the dermis or epidermis. The lesion most often associated with pressure was necrosis of the panniculus carnosus muscle, often accompanied by damage to underlying adipose tissue. Recurrent pressure results in increasingly severe damage to the vascular system and parenchyma, consistent with an ischemia/reperfusion insult initiated through a free radical mechanism. PMID- 7889252 TI - A historical perspective on specialty beds and other apparatus for treatment of invalids. AB - The bed environment and support surface have long been recognized as important in the care of the chronically ill. A review of specialty beds from the 19th and early 20th century was done from the collection of medical trade catalogs at the New York Academy of Medicine. It has been said "Past Is Prologue." Whether or not this is true, examination of selected examples of these historical beds can provide an unique and interesting perspective on contemporary practice. PMID- 7889254 TI - Put your money. PMID- 7889253 TI - Position changes for residents in long-term care. AB - The purpose of this study in long-term care facilities was to determine the factors associated with the common pressure ulcer prevention practice of turning and positioning of residents. The study showed there was a deficit in performance of two-hour turning, but not in knowledge that turning should be done. The chief reason for the aides' performance deficit was a lack of specific assignment to the task as well as a lack of time and staff. Head nurses and directors of nursing acknowledged these problems and also cited copious paperwork that prevented them from spending the necessary time to monitor compliance to facility policies on turning and positioning. PMID- 7889255 TI - Prevention by dexamethasone of the marked antiarrhythmic effects of preconditioning induced 20 h after rapid cardiac pacing. AB - Dogs were paced, via a pacing electrode in the right ventricle, for four 5 min periods at a rate of 220 beats min-1. On the following day they were reanaesthetized, thoracotomized and the left anterior descending coronary artery occluded for 25 min. Pacing markedly reduced the severity of ischaemia-induced arrhythmias (e.g. reduction in VF from 45% in unpaced dogs to 10% in paced dogs; P < 0.05), an effect reversed by dexamethasone (4 mg kg-1 i.v., 45 min prior to pacing). This protection may be due to the induction of nitric oxide synthase or cyclo-oxygenase. PMID- 7889256 TI - Attenuation by dexamethasone of endotoxin protection against ischaemia-induced ventricular arrhythmias. AB - Ventricular arrhythmias from a 30 min occlusion of the left coronary artery were assessed in Langendorff perfused isolated hearts removed from rats administered either saline, or endotoxin derived from Escherichia coli (2.5 mg kg-1 i.p.) given either 2, 4, 8, 24 or 48 h previously. Arrhythmia severity was markedly reduced in those hearts removed from rats administered endotoxin with a maximum protection at 8h; there was a marked reduction in the incidence of ventricular fibrillation (from 54% to 4%) and in the number of ventricular premature beats during the occlusion period (e.g. from 1165 +/- 144 to 37 +/- 19; P < 0.01). Dexamethasone (3 mg kg-1, given 1 h prior to endotoxin or saline) markedly attenuated the protection afforded by endotoxin. PMID- 7889257 TI - Modulation by endogenous ATP of the light-evoked release of ACh from retinal cholinergic neurones. AB - The retina is an area of the central nervous system that possesses intrinsic cholinergic neurones which release acetylcholine (ACh) in response to stimulation with flickering light. Using an eye-cup preparation in anaesthetized rabbits we found that when the retina was exposed to the P2-purinoceptor antagonist, PPADS, the light-evoked release of ACh was strikingly increased (by over 40%). In contrast, ATP reduced the light-evoked release of ACh by 20%. The inhibitory effect of ATP was not due to its catabolism to adenosine because it was not affected by the A1-adenosine receptor antagonist, DPCPX, in combination with adenosine deaminase. The actions of both ATP and PPADS were completely blocked by strychnine. We conclude that during physiological stimulation of the retina with light, ATP is co-released with ACh and partially inhibits ACh release by activating (with ACh) an inhibitory glycinergic feedback loop. PMID- 7889258 TI - Smooth muscle relaxing effects of NO, nitrosothiols and a nerve-induced relaxing factor released in guinea-pig colon. AB - 1. The aim of the present study was to compare the biological activity of S nitroso-L-cysteine (CYSNO), S-nitrosoglutathione (GSNO), S-nitroso-N-acetyl-D,L penicillamine (SNAP) and hydroxylamine to that of nitric oxide (NO) and a vascular relaxing factor released by nerve stimulation in the guinea-pig intestine. The biological activity was examined in a bioassay system with guinea pig colon as donor tissue and a series of spiral strips of rabbit aorta without endothelium as detector tissues. 2. Electrical stimulation of the guinea-pig colon released a vascular relaxing factor. The half-life of the relaxing factor down the bioassay cascade was the same as exogenously applied NO. N omega-nitro-L arginine (L-NOARG) inhibited the release of bioactivity. 3. The relaxations of the assay tissues caused by exogenous CYSNO also declined during the passage down the cascade. However, in the presence of L-cysteine (10(-5) M) the half-life of CYSNO increased and there was no significant breakdown through the cascade. In contrast, the half-life of applied NO and the vascular relaxing factor released by nerve stimulation was unaffected by the presence of L-cysteine. 4. Exogenously applied GSNO (20-50 nM), SNAP (2-4 nM) and hydroxylamine (300-600 nM) caused relaxations that did not decline during the passage down the cascade. 5. In summary, the relaxation of the bioassay tissues during nerve stimulation was indistinguishable from the relaxation induced by NO, whereas relaxations induced by CYSNO, GSNO, SNAP and hydroxylamine showed different pharmacological profiles. The released bioactivity is thus likely to be NO itself. PMID- 7889259 TI - Pharmacological reactivity of human epicardial coronary arteries: phasic and tonic responses to vasoconstrictor agents differentiated by nifedipine. AB - 1. Human epicardial coronary artery rings, freshly obtained from cardiac transplantation patients, commonly exhibited phasic contractile activity in vitro. This activity occurred either spontaneously or in response to vasoconstrictor stimulation. 2. Nifedipine pretreatment (1 nM-0.1 microM) reduced both types of phasic contractions in a concentration-dependent manner. At 0.1 microM nifedipine, spontaneous contractions were completely abolished, as were phasic contractions induced by U46619, endothelin-1 or 5-hydroxytryptamine (5 HT). 3. For U46619 (0.1-100 nM), the largest phasic contractions (amplitude peak to trough) occurred over the mid-range of concentrations used (1-10 nM). At higher concentrations (30-100 nM), phasic activity was reduced as the response reached a maximum. Estimated pEC50 values for the upper phasic and lower phasic curves were significantly different (8.71 +/- 0.13 versus 7.90 +/- 0.11; P < 0.05; n = 10). In the presence of nifidepine (0.1 microM), the purely tonic contraction curve to U46619 was similar to the lower phasic curve in the absence of nifedipine (pEC50 = 8.14 +/- 0.06, n = 10). Similar results were obtained for endothelin-1 (0.1-100 nM). 4. Responses to 5-HT (1 nM-3 microM) were more variable. The largest phasic contractions were spread unevenly throughout the concentration-response curve. In the presence of nifedipine (0.1 microM), the curve to 5-HT was significantly depressed in range but not sensitivity (pEC50) when compared with the phasic curves. 5. In conclusion, activation of dihydropyridine-sensitive voltage-operated Ca2+ channels mediated the phasic contractions commonly observed in human epicardial coronary arteries. These contractions amplified the contractile responses to low concentrations of vasoconstrictors. Inhibition of phasic activity by the Ca2+ channel antagonist, nifedipine, allowed the tonic vasoconstrictor profile of human isolated coronary artery to be determined which is important information for the accurate quantitative assessment of vasodilator responses in this tissue in vitro. PMID- 7889260 TI - Pharmacological reactivity of human epicardial coronary arteries: characterization of relaxation responses to endothelium-derived relaxing factor. AB - 1. Human epicardial coronary artery rings, freshly obtained from cardiac transplant patients, were examined for their responses to endothelium-derived relaxing factor (EDRF)-releasing agents. 2. Functional antagonism profoundly influenced relaxation responses in this tissue. Increasing force with concentrations of U46619 above 3 nM (40% of maximum contraction response) resulted in a reduction of the maximum response to four vasorelaxants which relax vascular smooth muscle via different mechanisms: the EDRF-releasing agents, substance P and bradykinin; the endothelium-independent nitro-vasodilator, sodium nitroprusside (SNP); and the beta-adrenoceptor agonist, isoprenaline. 3. Substance P, histamine, bradykinin and the Ca2+ ionophores ionomycin and A23187 all caused concentration- and endothelium-dependent relaxation in vessels pre contracted with the thromboxane A2-mimetic, U46619 (3 nM) to an active force optimal for relaxation responses. Nifedipine (0.1 microM), added to prevent spontaneous contractions, had no effect or relaxation responses to substance P, bradykinin and histamine. 4. Substance P was the most potent of the EDRF releasing agents examined and all agents except for bradykinin caused near maximal relaxation. Bradykinin caused only 46.2% +/- 7.3% relaxation. Responses were abolished when the endothelium was removed and, except for histamine, were not significantly affected by indomethacin (3-10 microM, P > 0.05). Histamine (0.1-10 microM) caused a concentration-dependent contraction of arterial rings without endothelium. 5. The L-arginine analogues NG-nitro-L-arginine (L-NOARG, 0.1 mM) and NG-monomethyl-L-arginine (L-NMMA, 0.1 mM) both caused no further contraction in arteries precontracted with U46619 (3 nM) and were in general, poor inhibitors of responses to EDRF agonists. L-NMMA, but not L-NOARG,caused small but significant decreases in the maximum responses to substance P, bradykinin (18.5 +/- 6.9% and 27.6 +/- 10.9% relaxation with L-NMMA and L-NOARG, respectively), histamine and A23187 (P<0.05). The analogues had no effect on SNP responses.6. In conclusion, EDRF release in human isolated coronary artery is only poorly antagonized by the nitric oxide synthase inhibitors L-NOARG and L NMMA. These results indicate that either the nitricoxide transduction pathway present in human coronary artery is different from that in other tissues or that another factor(s) (e.g. endothelium-derived hyperpolarizing factor) is also released in response to EDRF-releasing agents and augments the relaxation to nitric oxide. PMID- 7889261 TI - Blockade of noradrenaline-induced constrictions by yohimbine and prazosin differs between consecutive segments of cutaneous arteries in guinea-pig ears. AB - 1. The study has examined the receptors mediating constriction produced by brief local application of noradrenaline (NA) to cutaneous arteries and arterioles in the ear vasculature of anaesthetized guinea-pigs. The innervation of the corresponding vascular segments has been examined immunohistochemically at the conclusion of the pharmacological experiments. 2. Small arteries of branch order 4 (4 degrees, 40-110 microns internal diameter) were more sensitive to the vasoconstrictor action of NA than were more proximal arteries of branch order 3 (3 degrees, 60-150 microns internal diameter), or more distal arteries and arterioles of branch orders 5 to 7 (5 degrees-7 degrees, 18-85 microns internal diameter). This higher sensitivity of 4 degrees arteries was maintained after blockade of neuronal uptake with desipramine (1 microM), and after blockade of beta-adrenoceptors with propranolol (1 microM). 3. NA-induced vasoconstrictions of distal arterioles (5 degrees-7 degrees) were abolished or greatly reduced by yohimbine (1 microM). The blockade by yohimbine decreased progressively with increasing vessel diameter of proximal arteries, while the blockade by prazosin (1 microM) increased progressively in arteries > 40 microns diameter. 4. In 3 degrees and 4 degrees arteries, a substantial component (approximately 50%) of NA induced vasoconstrictions remained after combined treatment with yohimbine and prazosin, in the presence or absence of desipramine. These constrictions were not further reduced by benextramine (1-10 microM), but were abolished by dihydroergotamine (1-10 microM). Constrictions induced by ATP (0.1-1 mM) were not affected by dihydroergotamine. 5. 5-Hydroxytryptamine (3-100 microM) had a variable effect on 3 degree and 4 degree arteries including: concentration dependent constrictions (n = 3); small constrictions at some concentrations, and dilatations or no change in diameter at other concentrations (n = 6); concentration-dependent dilatations only (n = 3). The 5-HT2 receptor antagonist, ketanserin (0.1-0.3 micro M), did not affect NA-induced constrictions.6. In 16 arterial segments ranging from 3 degree arteries to 60 arterioles, there was a significant correlation between the presence of neuropeptide Y-immunoreactive (NPY-IR) sympathetic axons and the degree of blockade of NA-induced constrictions by yohimbine, prazosin and dihydroergotamine.7. These results demonstrate marked differences in the postsynaptic adrenoceptors mediating vasoconstriction to a bolus of NA applied briefly to the adventitial surface of different segments of the cutaneous vasculature of the guinea-pig ear. Furthermore, the presence or absence of adrenoceptors sensitive to blockade by yohimbine or prazosin is related to the proportion of sympathetic axons innervating each vascular segment which contain NPY-IR. PMID- 7889262 TI - Effects of tenoxicam and aspirin on the metabolism of proteoglycans and hyaluronan in normal and osteoarthritic human articular cartilage. AB - 1. As nonsteroidal anti-inflammatory drugs may impair the ability of the chondrocyte to repair its damaged extracellular matrix, we explored the changes in the metabolism of newly synthesized proteoglycan (PG) and hyaluronan (HA) molecules produced by tenoxicam and aspirin in human normal cartilage explants and in osteoarthritic (OA) cartilage from age-matched donors. 2. Explants were sampled from the medial femoral condyle and were classified by use of Mankin's histological-histochemical grading system. Cartilage specimens were normal in 10 subjects, exhibited moderate OA (MOA) in 10 and had severe OA (SOA) in 10. 3. Cartilage explants were pulsed with [3H]-glucosamine and chased in the absence and in the presence of either aspirin (190 micrograms ml-1) or tenoxicam (4-16 micrograms ml-1). After papain digestion, the labelled chondroitin sulphate ([3H] PGs) and HA([3H]-HA) molecules present in the tissue and media were purified by anion-exchange chromatography. 4. In normal cartilage as well as in explants with MOA and SOA aspirin reduced more strongly PG and HA synthesis than the loss of [3H]-HA and [3H]-PGs. 5. In normal cartilage, tenoxicam did not affect PG metabolism whereas it reduced HA synthesis in a dose-dependent manner and did not change or even increased the net loss of [3H]-HA. In contrast, in OA cartilage, tenoxicam produced a stronger reduction in the loss of [3H]-PGs than in PG synthesis and this decrease occurred at lower concentrations in cartilage with SOA (4-8 micrograms ml-1) than in cartilage with MOA (8-16 micrograms ml-1). In cartilage with MOA, the metabolic balance of HA was unaffected by tenoxicam whereas in cartilage with SOA, the drug decreased the loss of [3H]-HA and concomitantly did not change or even increased HA synthesis.6. The data obtained in short-term in vitro cultures indicate that aspirin may produce OA-like changes in normal cartilage and is likely to worsen the disease process in OA tissue. On the other hand, although tenoxicam may reduce the HA content of normal cartilage, and, in so doing, may produce OA-like lesions, this drug should not per se accelerate joint failure in OA. PMID- 7889263 TI - Neutral endopeptidase (NEP) inhibition in rats with established pulmonary hypertension secondary to chronic hypoxia. AB - 1. Atrial natriuretic peptide (ANP) causes vasorelaxation in the pulmonary vasculature. ANP levels are elevated in conditions characterized by pulmonary hypertension and it has been hypothesized that ANP may be autoregulatory in the pulmonary circulation. 2. One route of ANP metabolism in vivo is by the action of the enzyme neutral endopeptidase (NEP). We have studied the effects of the NEP inhibitor, SCH 42495, in rats with established pulmonary hypertension secondary to chronic hypoxia. 3. Rats (n = 32) were divided into 4 groups. Normoxic controls were kept in air for 10 days (NC10) and all other animals were placed in a normobaric hypoxic chamber (F1 O2 10%). Chronic hypoxic controls were studied at 10 days (CHC10). After 10 days hypoxia the two remaining groups received oral treatment for a further 10 days, consisting of either SCH 42495 (30 mg kg-1, twice daily CHT20) or methyl cellulose vehicle (0.4%, twice daily, CHV20). 4. Animals were anaesthetized and blood collected for measurement of plasma ANP. Hearts were dissected and ventricles weighed and the histology of the pulmonary vasculature examined. 5. CHC10 rats had significant right ventricular hypertrophy (0.53 +/- 0.08) and pulmonary vascular remodelling (29.0 +/- 0.01%) and had gained significantly less body weight (33.2 +/- 5.5 g) than NC10 rats (0.31 +/- 0.04, 10.9 +/- 0.01%, and 59.2 +/- 11.9 g respectively). CHC10 rats had significantly elevated plasma ANP levels (58.4 +/- 9.9 pM) compared with NC10 rats (23.9 +/- 32 pM). Treatment with SCH 42495 caused a significant reduction in pulmonary vascular remodelling (25.0 +/- 0.01%) and right ventricular hypertrophy (0.52 +/- 0.09) in CHT20 rats compared with CHV20 controls (33.0 +/- 0.02% and 0.61 +/- 0.09 respectively). Pulmonary vascular remodelling was also significantly lower in CHT20 rats than CHC1O animals.6. Thus, short term inhibition of NEP causes regression of established pulmonary vascular remodelling and may be a useful therapeutic strategy in pulmonary hypertension. PMID- 7889264 TI - Dissociation of castor oil-induced diarrhoea and intestinal mucosal injury in rat: effect of NG-nitro-L-arginine methyl ester. AB - 1. Castor oil (2 ml orally) produced diarrhoea in rats 1-7 h after challenge, which was associated with gross damage to the duodenal and jejunal mucosa. 2. The injury was accompanied by release of acid phosphatase into the gut lumen, indicating cellular injury. 3. Intraperitoneal injection of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 2.5-50 mg kg-1 twice), prevented the diarrhoea. The dose of L-NAME (50 mg kg-1) completely blocked the diarrhoea but increased the release of acid phosphatase and worsened the gross damage. 4. The NO donating compound, isosorbide-5-mononitrate (IMN, 150 mg kg-1 twice) reversed the effects of L-NAME (50 mg kg-1) on castor oil-induced diarrhoea, gross damage and acid phosphatase release. 5. The apparent dissociation of the diarrhoeal and intestinal mucosal damaging effects of castor oil suggest that NO has a protective effect on the rat duodenal and jejunal mucosa, but that NO mediates, in part, the diarrhoea effect of this laxative. PMID- 7889265 TI - Interactions of constitutive nitric oxide with PAF and thromboxane on rat intestinal vascular integrity in acute endotoxaemia. AB - 1. The involvement of endogenous platelet activating factor (PAF) and thromboxane A2 in the acute microvascular damage in the ileum and colon induced by the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) following endotoxin administration was investigated in the rat over a 1 h period. 2. Administration of L-NAME (1-10 mg kg-1, s.c.) concurrently with E. coli lipopolysaccharide (LPS; 3 mg kg-1, i.v.) dose-dependently increased vascular permeability in the ileum and colon, as determined by the leakage of radiolabelled albumin, and caused macroscopic mucosal damage in the ileum determined 1 h later. Neither LPS administration nor L-NAME (5 mg kg-1) alone affected resting vascular permeability. 3. Infusion of phenylephrine (10 micrograms kg-1 min-1, i.v. for 1 h) caused an elevation in blood pressure similar to that found following L-NAME administration (5 mg kg-1, i.v. or s.c.), but did not increase intestinal vascular permeability, when administered with LPS (3 mg kg-1, i.v.). 4. The increased vascular permeability in the ileum and colon and macroscopic damage in the ileum, induced by L-NAME (5 mg kg-1, s.c.) and LPS (3 mg kg-1, i.v.) was dose-dependently inhibited following s.c. pretreatment (15 min before challenge) with the thromboxane synthase inhibitors, OKY 1581 (5-25 mg kg-1) or 1-benzyl-imidazole (1-50 mg kg-1), or with the thromboxane receptor antagonist, BM 13177 (0.2-2 mg kg-1). 5. Pretreatment with the cyclo-oxygenase inhibitor, indomethacin (2-5 mg kg-', s.c., 15 min before challenge) reduced the microvascular injury in the ileum and colon and macroscopic lesions in the ileum,observed after the concurrent administration of L-NAME and LPS.6. Pretreatment (15 min) with the PAF-receptor antagonists, WEB 2086 (0.5-1 mg kg-', s.c.) or BN52021 (2.5-10 mg kg-', s.c.) likewise attenuated this intestinal vascular injury.7. Combined administration of low doses of l-benzyl-imidazole (1 mg kg-') with WEB 2086(0.5 mg kg-')15 min before L-NAME and LPS challenge, abolished this vascular damage and macroscopic injury.8. These results suggest that PAF and thromboxane A2 are released acutely following challenge with a low dose of endotoxin. However, these mediators do not appear to injure the intestinal micro vascular bed unless NO synthase is concurrently inhibited. Such findings support the protective role of constitutively-formed NO, counteracting the injurious vascular actions of cytotoxic mediators released under pathological conditions. PMID- 7889266 TI - Antianginal effects of FK409, a new spontaneous NO releaser. AB - 1. The aim of this study was to compare antianginal effects of (+/-)-(E)-ethyl-2 [(E)-hydroxyimino]-5-nitro-3-hexeneamide (FK409), a new spontaneous nitric oxide releaser, with those of isosorbide dinitrate (ISDN). We used two types of rat angina model; methacholine- and arginine vasopressin (AVP)-induced coronary vasospasm models. 2. In the in vitro study, FK409 showed 80 times more potent vasorelaxant effect in dog isolated coronary artery than ISDN (EC50 = 16.7 +/- 4.8 and 1340 +/- 320 nM, respectively). 3. In the rat methacholine-induced coronary vasospasm model, FK409 suppressed the elevation of ST segment dose dependently and significantly at 0.1 mg kg-1, i.d. On the other hand, ISDN suppressed it significantly at 3.2 mg kg-1, i.d. In addition, the efficacy of 3.2 mg kg-1 ISDN in the model was almost the same as that of 0.1 mg kg-1 FK409. 4. In the above experiments, FK409 and ISDN decreased mean blood pressure significantly at the maximum dose tested (1.0 mg kg-1, i.d. and 3.2 mg kg-1, i.d., respectively) but did not change heart rate at these doses. Therefore, the hypotensive effect of FK409 was 10 times weaker than the antianginal effect of the compound, while those of ISDN were almost the same. 5. In the rat AVP-induced coronary vasospasm model, 32 mg kg-1 FK409 significantly inhibited the depression of ST segment 60 min after oral administration. On the other hand, 32 mg kg-1 ISDN did not inhibit it at 60 and 120 min after oral administration. 6. In conclusion, FK409 inhibits coronary vasospasm more potently in two types of rat angina models than ISDN. In addition, FK409 shows an antianginal effect more selectively that a hypotensive effect,compared with ISDN. PMID- 7889267 TI - Evidence for reduction of bradykinin-induced bronchoconstriction in guinea-pigs by release of nitric oxide. AB - 1. In this study the influence of nitric oxide (NO) on the bronchoconstriction induced by bradykinin in anaesthetized and artifically ventilated guinea-pigs pretreated with atropine was investigated. 2. Aerosol administration of bradykinin (0.1-1 mM, 40 breaths) caused a dose-dependent increase in lung resistance (RL): maximum increase in RL was 2.5 fold the baseline value. Pretreatment with aerosolized NG-nitro-L-arginine methyl ester (L-NAME) or NG monomethyl-L-arginine (L-NMMA) (1 mM, 10 breaths every 5 min for 30 min), NO synthase inhibitors, markedly increased the bronchoconstrictor response to bradykinin. L-Arginine, but not D-arginine, (3 mM, 10 breaths every 5 min for 30 min) reversed the hyperresponsiveness to aerosolized bradykinin caused by L-NAME and L-NMMA. 3. L-NAME (1 mM, 10 breaths every 5 min for 30 min) increased the bronchoconstriction induced by intravenous bradykinin (1-10 nmol kg-1). L Arginine, but not D-arginine, (10 breaths every 5 min for 30 min) reversed the hyperresponsiveness to intravenous bradykinin caused by L-NAME. 4. The increase in RL induced by capsaicin, either aerosol (10 microM, 10 breaths) or i.v. (20 nmol kg-1) was not affected by L-NAME (1 mM, 10 breaths every 5 min for 30 min). Acute resection of the vagi did not affect the bronchoconstriction evoked by bradykinin in guinea-pigs, either in the absence or presence of L-NAME (1 mM, 10 breaths every 5 min for 30 min). 4. These results suggest that, irrespective of the route of administration, bradykinin releases NO or a related molecule which exerts a bronchodilator action that opposes the bronchoconstrictor mechanisms activated by bradykinin itself. PMID- 7889268 TI - Participation of tumour necrosis factor and nitric oxide in the mediation of vascular dysfunction in splanchnic artery occlusion shock. AB - 1. Splanchnic artery occlusion (SAO) shock is characterized by irreversible circulatory failure. Tumour necrosis factor (TNF-alpha) may affect the L arginine/nitric oxide (NO) pathway, thus contributing to the cardiovascular derangements of circulatory shock. 2. We investigated the contribution of both TNF-alpha and the L-arginine/nitric oxide pathway to the vascular dysfunction of SAO shock. Anaesthetized rats, subjected to total occlusion of the superior mesenteric artery and the coeliac trunk for 45 min developed a severe shock state (SAO shock) resulting in a fatal outcome within 75-90 min after the release of occlusion. Sham operated animals were used as controls. SAO shocked rats had also a marked hypotension and enhanced macrophage and serum levels of TNF-alpha. Furthermore, aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE 1 nM-10 microM) and reduced responsiveness to acetylcholine (ACh 10 nM-10 microM). Endothelium-denuded aortic rings had also a marked hyporeactivity to phenylephrine, which was restored to control values by in vitro administration of NG nitro-L-arginine-methyl ester (L-NAME 10 microM). 3. In vivo administration of cloricromene (2 mg kg-1, i.v.), an inhibitor of TNF-alpha biosynthesis, increased survival, enhanced mean arterial blood pressure and reduced macrophage and serum levels of TNF-alpha. Furthermore, aortic rings from shocked rats treated with cloricromene exhibited a greater contractile response to phenylephrine and improved responsiveness to ACh when compared to aortic rings from vehicle-treated SAO shocked rats. 4. Our results suggest that TNF-alpha alters both endothelial and muscular L-arginine/nitric oxide pathways which in turn produce vascular dysfunction in SAO shock. PMID- 7889269 TI - The effects of administration of monoamine oxidase-B inhibitors on rat striatal neurone responses to dopamine. AB - 1. (-)-Deprenyl has been shown to potentiate rat striatal neurone responses to dopamine agonists at doses not altering dopamine metabolism. Since there are a number of effects of (-)-deprenyl which could result in this phenomenon, we have investigated the effects of MDL 72,145 and Ro 19-6327, whose only common effect with (-)-deprenyl is an inhibition of monoamine oxidase-B (MAO-B), on rat striatal neurone responses to dopamine and on striatal dopamine metabolism. 2. Using in vivo electrophysiology, i.p. injection of either MDL 72,145 or Ro 19 6327 was found to produce a dose-dependent potentiation of striatal neurone responses to dopamine but not gamma-aminobutyric acid. 3. Neurochemical investigations revealed that this occurred at doses (0.25-1 mg kg-1) which, while not affecting levels of dopamine or its metabolites, 3,4-dihydroxyphenylacetic acid or homovanillic acid, did cause a significant, dose-dependent, elevation in striatal levels of the putative neuromodulator, 2-phenylethylamine (PE). 4. Inhibition of PE synthesis by i.p. injection of the aromatic L-amino acid decarboxylase inhibitor, NSD 1015, produced a reversal of the effects of MDL 72,145 and Ro 19-6327. 5. Neurochemical analysis revealed this to occur at a dose of NSD 1015 (10 mg kg-1) selective for reduction of elevated PE levels. 6. These results suggest that PE can act as a neuromodulator of dopaminergic responses and that MAO-B inhibitors may potentiate neuronal responses to dopamine via the indirect mechanism of elevation of PE following MAO-B inhibition. PMID- 7889270 TI - The effects of a novel vasodilator, LP-805, on cytosolic Ca2+ concentrations and on tension in rabbit isolated femoral arteries. AB - 1. LP-805, 8-tert-butyl-6,7-dihydropyrrolo-[3,2-e]-5-methylpyrazolo- [1,5a] pyrimidine-3-carbonitrile, is a newly synthesized potent vasodilator. To investigate the cellular mechanisms of vasorelaxation induced by LP-805, we simultaneously determined the effects of LP-805 on cytosolic Ca2+ concentrations ([Ca2+]i) and on tension of smooth muscle of rabbit femoral arterial strips, with or without the endothelium, using front-surface fluorometry and fura-2. 2. In the absence of the endothelium, LP-805, in a concentration-dependent manner, decreased [Ca2+]i and tension during the contraction induced by K(+) depolarization, at relatively low concentrations ([K+]o < or = 30 mM). The decreases in [Ca2+]i and tension were fully antagonized by treatment with 2 x 10( 6) M glibenclamide. The [Ca2+]i-tension relationship in the LP-805-induced relaxation was similar to that of K(+)-depolarization-induced contractions. 3. LP 805, in a concentration-dependent manner (IC50 for inhibition of tension; 1.7 x 10(-6) M), decreased both [Ca2+]i and tension during the steady-state of contractions induced by 1 x 10(-7) M noradrenaline (NA) in the strips without the endothelium. Glibenclamide completely inhibited these reductions of [Ca2+]i and tension. At the steady-state of relaxation induced by LP-805 during NA-induced contraction, [Ca2+]i-tension relation was shifted to the left of that obtained with high K(+)-induced contraction. 4. NA induced transient increases in [Ca2+]i and tension in the absence of extracellular Ca2+. LP-805 (up to 3 x 10(-6) M) had no effect on these intracellular Ca2+ mobilisation and tension development induced by NA. 5. In strips with an intact endothelium, LP-805 decreased both [Ca2+]i and tension during contraction induced by 1 x 10(-7) M NA. The concentration-response curve for inhibition of [Ca2+]i and tension obtained in the presence of the endothelium was shifted to the left from that obtained in the absence of endothelium. IC50 for the inhibition of tension obtained in the strips with the endothelium was 4.0 x 10(-7) M. Treatment with 1 x 10(-4) M NG-nitro-L arginine (L-NOARG) attenuated reductions of both [Ca2+]i and tension induced by LP-805 and the concentration-response curve shifted to the right and overlapped that obtained in the absence of the endothelium. Treatment with glibenclamide almost fully overcame the reduction of [Ca2+]i induced by LP-805, while the reversion of tension was 50% at most. 6. In the presence of the endothelium with L-NOARG, LP-805 reduced the tension to the extent of that expected from the reduction of [Ca2'ji, as based on the [Ca2+]i-tension relationship obtained with LP-805 in the absence of endothelium. On the contrary, in the presence of the endothelium without L-NOARG, LP-805 induced a greater reduction of tension than expected from the reduction of [Ca2+J1.This effect became more apparent after treatment with glibenclamide.7. These results suggest that: (1) LP-805 relaxes smooth muscle mainly by activating ATP-sensitive K+channels of smooth muscle and by releasing endothelium-derived relaxing factor (EDRF). (2) Activation of ATP sensitive K+ channels decrease [Ca2+]i and thereby relax smooth muscle with no effect on Ca2"-sensitivity of the contractile apparatus of smooth muscle or on the agonist-induced Ca2"-release process. (3) EDRF induced by LP-805 relaxes smooth muscle not only by decreasing [Ca2+]i but also decreasing Ca2+-sensitivity of the contractile apparatus of smooth muscle. In the presence of an intact endothelium, a decrease in Ca2+-sensitivity of the contractile apparatus may play an important role in LP-805-induced relaxation. PMID- 7889271 TI - 'Sensory-efferent' neural control of mucus secretion: characterization using tachykinin receptor antagonists in ferret trachea in vitro. AB - 1. We characterized the tachykinin receptor(s) mediating 'sensory-efferent' neural control of release of 35SO4-labelled macromolecules (mucus) from ferret trachea in vitro in Ussing chambers using selective tachykinin antagonists. Secretion was induced by substance P (SP), neurokinin A (NKA), capsaicin, the NK1 tachykinin receptor agonist [Sar9, Met(O2)11]substance P ([Sar9]SP), or acetylcholine (ACh), or by electrical stimulation of nerves. Antagonists used were FK888 and L-668,169, selective for the NK1 receptor, SR 48968, selective for the NK2 receptor, and FK224, a dual antagonist at NK1 and NK2 receptors. The selectivity of FK888 and SR 48968 was examined on NKA-induced contraction of ferret tracheal smooth muscle in vitro. 2. SP (1 microM) increased mucus secretion by 695% above vehicle controls. FK888 (0.1 microM-30 microM) inhibited SP-induced secretion in a dose-dependent manner, with complete inhibition at 10 microM and an IC50 of 1 microM. L-668,169 (1 microM) also completely inhibited SP induced secretion. 3. NKA (1 microM) significantly increased mucus secretion by 271% above baseline, a response which was completely inhibited by FK888 (10 microM) or L-668,169 (microM). Secretion induced by ACh (10 microM: 317% above baseline) was not inhibited by FK888 but was inhibited by atropine. Capsaicin (10 microM)-induced secretion (456% above vehicle controls) was significantly inhibited by FK888 and by L-668,169 (111% and 103% inhibition respectively). 4. Electrical stimulation (50 V, 10 Hz, 0.5 ms, 5 min) increased mucus output above baseline (increased by 12 to 26 fold), a response blocked by tetrodotoxin (0.1 microM). FK888 (10 microM) inhibited the increase in secretion due to electrical stimulation by 47%. Atropine, propranolol and phentolamine in combination(APP) inhibited the response to electrical stimulation by 48%. The remaining NANC response, i.e. in the presence of APP, was further reduced by 66% with FK888. FK224 (10 microM) inhibited neurally evoked secretion by 73%. SR 48968 (0.1 fLM) had no effect on electrically-stimulated or [Sar9]SP-induced secretion.5. NKA (10nM- 1O microM: in the presence of DMSO control vehicle) induced tracheal smooth muscle contraction in a concentration-dependent manner with a maximal contraction of 30% of the maximal response to ACh (10 mM) and an ECm of 0.3 JAM. SR 48968 (0.1 microM in DMSO) inhibited the NKA induced contraction whereas FK888 did not. Neither antagonist had any inhibitory effect on ACh induced contraction.6. We conclude that 'sensory-efferent' neurogenic mucus secretion in ferret trachea in vitro is mediated via tachykinin NK, receptors with no involvement of NK2 receptors. Potent and selective tachykinin antagonists may have therapeutic potential in bronchial diseases such as asthma and chronic bronchitis in which neurogenic mucus hypersecretion may be aetiologically important. PMID- 7889272 TI - Contractile effects of uridine 5'-triphosphate in the rat duodenum. AB - 1. Previous studies have shown that the rat duodenum relaxes to adenosine and adenosine 5'-triphosphate (ATP) via P1 and P2Y purinoceptors respectively, but in preliminary studies uridine 5'-triphosphate (UTP) was found to contract this tissue. The non-selective P2 antagonist suramin and a number of nucleotides were therefore used to investigate this response further. 2. ATP, UTP, adenosine 5' diphosphate (ADP), adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S), guanosine 5'-triphosphate (GTP) and uridine 5'-diphosphate (UDP) each relaxed the duodenum, with an agonist potency order of ATP = ADP > ATP-gamma-S >> GTP >> UTP = UDP, consistent with the presence of a P2Y purinoceptor mediating relaxation. 3. ATP gamma-S, UTP and UDP each contracted the duodenum with an agonist potency order of ATP-gamma-S > UTP > UDP, although maximal responses to these agonists were not obtained at a concentration of 267 microM (ATP-gamma-S) and 300 microM (UTP and UDP). No contractions were observed with any of the other agonists at concentrations up to 300 microM. 4. Indomethacin (25 microM) did not inhibit the contractions induced by UTP, indicating that they were not mediated via production of prostaglandins. 5. Suramin (100 microM and 1 mM) inhibited relaxations induced by ATP, shifting the concentration-response curve to the right, with the maximal response to ATP being decreased by the higher concentration of suramin (1 mM). Suramin (1 mM) inhibited relaxations induced by ATP-gamma-S, shifting the concentration-response curve to the right, and completely abolished contractions induced by ATP-gamma-S. In contrast, suramin (100 JAM and 1 mM) had no effect on contractions induced by UTP.Contractions induced by UTP were, however, less sustained in the presence of suramin, which also affected the basal tone of some tissues when precontracted with carbachol (0.1 microM). In the presence of suramin (I mM), no contractions to ATP were observed.6. These results confirm that in the rat duodenum there is a P2Y purinoceptor that mediates relaxation in response to a number of purine nucleotides, and at which the pyrimidine nucleotides UTP and UDP are almost inactive. There are also receptors at which UTP and ATP-y-S act to cause contraction.Suramin discriminates between the contractile effects of these two agonists, which may indicate the presence of a suramin-insensitive pyrimidinoceptor as well as a suramin-sensitive receptor for ATP-y-S.An alternative explanation is that the differential effects of suramin are via its actions as an antagonist in addition to its action as an ectonucleotidase inhibitor. PMID- 7889273 TI - In vitro studies of release of adenine nucleotides and adenosine from rat vascular endothelium in response to alpha 1-adrenoceptor stimulation. AB - 1. Noradrenaline-induced release of endogenous adenine nucleotides (ATP, ADP, AMP) and adenosine from both rat caudal artery and thoracic aorta was characterized, using high-performance liquid chromatography with fluorescence detection. 2. Noradrenaline, in a concentration-dependent manner, increased the overflow of ATP and its metabolites from the caudal artery. The noradrenaline induced release of adenine nucleotides and adenosine from the caudal artery was abolished by bunazosin, an alpha 1-adrenoceptor antagonist, but not by idazoxan, an alpha 2-adrenoceptor antagonist. Clonidine, an alpha 2-adrenoceptor agonist, contracted caudal artery smooth muscle but did not induce release of adenine nucleotides or adenosine. 3. Noradrenaline also significantly increased the overflow of ATP and its metabolites from the thoracic aorta in the rat; however, the amount of adenine nucleotides and adenosine released from the aorta was considerably less than that released from the caudal artery. 4. Noradrenaline significantly increased the overflow of ATP and its metabolites from cultured endothelial cells from the thoracic aorta and caudal artery. The amount released from the cultured endothelial cells from the thoracic aorta and caudal artery. The amount released from the cultured endothelial cells from the aorta was also much less than that from cultured endothelial cells from the caudal artery. In cultured smooth muscle cells from the caudal artery, a significant release of ATP or its metabolites was not observed. 5. These results suggest that there are vascular endothelial cells that are able to release ATP by an alpha 1 adrenoceptor-mediated mechanism, but that these cells are not homogeneously distributed in the vasculature. PMID- 7889274 TI - Antithrombotic actions of argatroban in rat models of venous, 'mixed' and arterial thrombosis, and its effects on the tail transection bleeding time. AB - 1. The antithrombotic action of argatroban, a synthetic thrombin inhibitor, was studied in three models of thrombosis in the rat, and in the tail transection bleeding time test. Heparin was studied as a reference anticoagulant. 2. In the model of venous thrombosis induced by thromboplastin followed by stasis of the abdominal vena cava, argatroban had an ED50 of 125 micrograms kg-1, when administered as an i.v. bolus 5 min prior to the thromboplastin injection: the ED50 of heparin was 42 micrograms kg-1, where ED50 is the dose which reduces the weight of the thrombus by 50% compared with that of the control animals. When the two compounds were administered by continuous i.v. infusion, argatroban (ED50 = 1.5 micrograms kg-1 min-1) had the same potency as heparin (ED50 = 1.2 micrograms kg-1 min-1). 3. Argatroban was active in the arterio-venous shunt model with an ED50 of 0.6 mg kg-1 when the compound was given as a bolus. The ED50 of heparin was 0.04 mg kg-1 under the same conditions. The two compounds had ED50 values of 6 micrograms kg-1 min-1 (argatroban) and 3 micrograms kg-1 min-1 (heparin), when administered by continuous i.v. infusion. 4. When tested against occlusive arterial thrombus formation by electrical stimulation of the left carotid artery, both compounds given as either an i.v. bolus or a continuous infusion led to dose dependent increases in the duration of post-lesion vessel patency. Heparin bolus was more active than argatroban on a weight basis, in that 2 mg kg-1 gave a similar increase in the time to occlusion as 8 mg kg-1 argatroban. As in the other models, when given as continuous infusions, argatroban (111% increase in time to occlusion at 20 tg kg-1, min-1) had similar activity to that of heparin (180% increase at 25 jg kg-1 min-1) on a weight basis. Hoever, the antithrombotic effects of argatroban were accompanied by only moderate changes in the coagulation parameters (thrombin time and activated partial thromboplastin time, APTT), whereas, even at a subthreshold dose of heparin (12.5 pg kg-1 min-1), both the thrombin time and the APTT were greater than 150 s.5. Infusions of both compounds caused dose-dependent increases in the tail transection bleeding time,with the dose of argatroban that doubles the bleeding time (11 I g kg-1 min 1) being five times greater than that of heparin (EDI, = 2.2 fig kg-1 min-1).6. These data show that, when administered as an intravenous infusion, argatroban is a potent antithrombotic agent in rat models of venous 'mixed' and arterial thrombosis, this effect can be obtained with a lower degree of systemic anticoagulation than with heparin in the arterial model, and argatroban has a lower haemorrhagic potential than that of heparin. PMID- 7889276 TI - Beta-adrenoceptors mediate inhibition of [3H]-acetylcholine release from the isolated rat and guinea-pig trachea: role of the airway mucosa and prostaglandins. AB - 1. Rat or guinea pig isolated tracheae were labelled with [3H]-choline to measure evoked tritium outflow, which reflects neuronal release of [3H]-acetylcholine. Tritium outflow was evoked either by electrical stimulation of the extrinsic vagal nerve (rat tracheae) or by 27 mM potassium (guinea pig tracheae). 2. In rat tracheae isoprenaline (0.01, 0.1 microM) inhibited evoked [3H]-acetylcholine release, whereas beta 2-adrenoceptor-selective agonists (fenoterol, formoterol, salbutamol) were ineffective. 3. The inhibitory effect of isoprenaline was abolished under the following conditions: (i) presence of propranolol (1 microM) or of the beta 1-selective antagonist CGP 20712 A (0.1 microM); (ii) removal of the mucosa at the start of the experiments; (iii) blockade of cyclooxygenase activity by 3 microM indomethacin. 4. In rat isolated tracheae prelabelled with [3H]-arachidonic acid, isoprenaline (0.1 microM) but not formoterol (0.01 microM) enhanced the outflow of [3H]-prostaglandins (PGD2, PGE2). This effect was blocked by 0.1 microM CGP 20712 A. 5. In guinea pig tracheae electrical stimulation of the extrinsic vagal nerve did not cause a constant release of [3H]-acetylcholine, but 27 mM potassium elicited a reproducible release of [3H]-acetylcholine. In this species both isoprenaline (0.1 microM) and formoterol (0.01 microM) inhibited evoked [3H]-acetylcholine release. Inhibition was abolished under the following conditions: (i) presence of propranolol (1 microM) or of the beta 2 selective antagonist ICI 118551 (0.3 microM); (ii) removal of the mucosa at the start of the experiments; (iii) blockade of cyclooxygenase activity by 3 microM indomethacin. 6. In conclusion, the present experiments have demonstrated that activation of beta-adrenoceptors localized in the mucosa mediates inhibition of [3H]-acetylcholine release from the neuroeffector junctions of the pulmonary, parasympathetic nerves most probably by the liberation of inhibitory prostaglandins from the airway mucosa. The adrenoceptor subtype involved differs in rat (beta 1 subtype) and guinea pig (beta 2 subtype) airways. PMID- 7889275 TI - Effect of activity at metabotropic, as well as ionotropic (NMDA), glutamate receptors on morphine dependence. AB - 1. The contribution of various excitatory amino acid (EAA) receptors (NMDA, AMPA/kainate and metabotropic) in the brain to the development of morphine dependence was examined. This was performed by measuring the severity of the precipitated withdrawal syndrome following chronic subcutaneous (s.c.) morphine and intracerebroventricular (i.c.v.) EAA antagonist treatment. 2. Continuous subcutaneous (s.c.) treatment with morphine sulphate (36.65 mumol day-1) produced an intense and reliable naloxone-precipitated withdrawal syndrome. 3. Chronic i.c.v. treatment with antagonists selective for metabotropic and NMDA receptors, but not AMPA/kainate receptors, significantly attenuated abstinence symptoms. Conversely, EAA antagonists had very little effect on non-withdrawal behaviours. 4. These results suggest that, as well as changes elicited by activation of NMDA receptors, metabotropic receptors and intracellular changes in the phosphatidylinositol (PI) second-messenger system or the cyclic adenosine 3',5' monophosphate (cAMP) second messenger system, to which EAA metabotropic receptors are linked, may be involved in the development of opioid dependence with chronic morphine treatment. PMID- 7889277 TI - Potentiation of the anti-obesity effect of the selective beta 3-adrenoceptor agonist BRL 35135 in obese Zucker rats by exercise. AB - 1. The effects of chronic treatments with a selective beta 3-adrenoceptor agonist and a selective alpha 2-adrenoceptor antagonist and their interactions with physical exercise training were studied in experimental obesity. 2. BRL 35135 (beta 3-agonist, 0.5 mg kg-1 day-1 p.o.), atipamezole (alpha 2-antagonist, 4.0 mg kg-1 day-1 p.o.) and placebo were given to genetically obese male Zucker rats. Half of the rats were kept sedentary whereas the other half were subjected to moderate treadmill exercise training. Body weight gain, cumulative food intake, the neuropeptide Y content of the hypothalamic paraventricular nucleus, brown adipose tissue thermogenic activity (measured as GDP binding), plasma insulin and glucose levels were measured after 3 weeks' treatment and exercise. 3. Treatment with BRL 35135 reduced weight gain by 19%, increased brown adipose tissue thermogenic activity 45-fold and reduced plasma insulin by 50%. Atipamezole slightly increased food intake and neuropeptide Y content in the paraventricular hypothalamic nucleus but had no effect on the other measured parameters. Exercise alone had no effect on weight gain, food intake or thermogenic activity, whereas it reduced plasma insulin and glucose levels. 4. The effect of BRL 35135 on weight gain and thermogenic activity was significantly potentiated by exercise; the reduction in weight gain was 56% in comparison with 19% in sedentary animals. Food intake was significantly reduced in the BRL 35135-treated-exercise-trained animals, although neither beta 3-agonist nor exercise alone affected it. 5. Based on the present results in genetically obese Zucker rats, combination of 03 agonist treatment with a moderate physical training may offer a new feasible approach to the therapy of obesity.- KEYWORDS: BRL 35135; atipamezole; P3 adrenoceptor agonism; M2-adrenoceptor antagonism; brown adipose tissue; thermogenesis;genetic obesity; Zucker rat; exercise; neuropeptide Y PMID- 7889278 TI - Differences in sensitivity to the specific protein kinase C inhibitor Ro31-8220 between small and large bronchioles of the rat. AB - 1. The involvement of protein kinase C (PKC) in constriction of small bronchioles has never been investigated. In this study we have examined the effects of the specific PKC inhibitors Ro31-8220 and Ro31-7549 and the non-specific inhibitor H7 on carbachol-, 5-hydroxytryptamine (5-HT)- and 4 beta-phorbol dibutyrate (4 beta PDBu)-induced contractions in large and small bronchioles. 2. The study was performed on isolated bronchioles of the rat with internal diameters of 574 microns +/- 11 (small, n = 128), and 1475 microns +/- 32 (large, n = 93), using a Mulvaney-Halpen small vessel myograph. 3. In these preparations 4 beta-PDBu had no effect if added on its own. However, after precontracting with 30 mM K+, 0.5 microM 4 beta-PDBu caused a contractile response of 110.4 +/- 7.0% TK (TK = maximum response to 75 mM K+ in small and 69.3 +/- 6.5% TK in large bronchioles. Ro31-8220, Ro31-7549 and H7 all showed concentration-dependent inhibition of this response. 4. In small bronchioles 10 microM Ro31-8220 shifted both the carbachol and 5-HT concentration-response curves to the right, and reduced the maximum response. In contrast, 10 microM Ro31-8220 had no significant effect on the EC50 to carbachol of larger bronchioles, although the maximum response was reduced, and had no significant effect on the 5-HT concentration-response curve. 200 microM H7 shifted the carbachol concentration--response curve to the right as well as reducing the maximal response in both small and large bronchioles. 5 Large bronchioles exhibited a greater rate of decay of carbachol-induced contraction than did small bronchioles. Pretreatment with Ro31-8220 accelerated the rate of decay.6 Pretreatment with 10 JM Ro3l-8220 caused a small reduction in the response to 75 mM K+ in both small and large bronchioles (small: to 87.8 +/- 3.0% TK; large: to 94.1 +/- 0.8% TK). H7 at 200 JM caused a much larger reduction in both preparations (small: to 75.1 +/- 3.0% TK); large: to 82.7 +/- 0.6% TK).7 Small bronchioles were more sensitive than larger bronchioles to agonists and phorbol ester. The protein kinase inhibitor Ro31-8220 could reduce agonist induced constriction in small and large bronchioles,as well as reducing or abolishing phorbol ester-induced contractions. Small bronchioles were more sensitive than large bronchioles to Ro31-8220. These results suggest that there is a significant PKC involvement in constriction of bronchioles to carbachol and 5-HT, and that the proportion of the contractile response that can be attributed to PKC is greater in smaller than larger bronchioles. PMID- 7889279 TI - Calcitonin gene-related peptide receptors in human gastrointestinal epithelia. AB - 1. The secretory responses to calcitonin gene-related peptide (CGRP) receptor agonists have been characterized in two human adenocarcinoma cell lines, namely HCA-7 and Colony-29 (Col-29) epithelia. These cells form polarized epithelial layers when grown on permeable supports and allow changes in electrogenic ion transport in response to agonists to be monitored continuously. 2. alpha-CGRP (rat and human sequences), rat beta-CGRP and human [Tyr0]CGRP applied to the basolateral surface were found to be full agonists, causing prolonged increases in short-circuit current. Concentration-response curves exhibited EC50 values of 0.6-1.5 nM in HCA-7 cells. The same agonists were less effective in Col-29 epithelia, the EC50 values ranging from 1 to 10 nM in these cells. [Cys(ACM)2,7]CGRP was effective in both cell lines and was more potent in HCA-7 cells. 3. CGRP receptors were preferentially located on the basolateral surface in both cell types. Addition of r alpha-CGRP to the apical domain produced significantly smaller secretory responses (8.1% in HCA-7 and 29.2% in Col-29) compared with those produced following basolateral application (100%). 4. In both cell lines r alpha-CGRP-elevated short-circuit current was inhibited by the loop diuretic piretanide (200 microM) and by somatostatin (100 nM). Pretreating epithelia with the cyclo-oxygenase inhibitor, piroxicam (5 microM) had no significant effect upon CGRP responses in either cell line. 5. Rat alpha-CGRP (0.2 nM) responses in HCA-7 epithelia were inhibited by the C-terminal fragment CGRP(8-37) (1 microM). Pretreatment of Col-29 cells with CGRP(8-37) did not, however, alter the size or profile of responses to r alpha-CGRP (1 nM).6. We conclude that high-affinity CGRP receptors exist on the basolateral surface of both cell lines,however they differ in their sensitivity to CGRP(8-37) and agonist orders of potency. Thus different CGRP receptor subtypes appear to predominate in these two epithelial cell types. PMID- 7889280 TI - The binding of 1,3-[3H]-dipropyl-8-cyclopentylxanthine to adenosine A1 receptors in rat smooth muscle preparations. AB - 1. The binding of 1,3-[3H]-dipropyl-8-cyclopentylxanthine ([3H]-DPCPX), an antagonist radioligand selective for adenosine A1 receptors, was studied in rat duodenum, colon muscularis mucosae and longitudinal muscle, urinary bladder and vasa deferentia. 2. [3H]-DPCPX bound with high affinity to a single site in all membrane preparations studied with the exception of the rat urinary bladder in which no specific binding was detected. The affinity (Kd) of the binding site for [3H]-DPCPX was similar in all membrane preparations, the colon longitudinal muscle (1.18 +/- 0.47 nM), colon muscularis mucosae (0.84 +/- 0.15 nM), duodenum (1.59 +/- 0.18 nM) and vasa deferentia (0.93 +/- 0.17 nM). The density of [3H] DPCPX binding sites was similar in the duodenum (38.8 +/- 4 fmol mg-1 protein), muscularis mucosae (43 +/- 3.5 fmol mg-1 protein) and vasa deferentia (43.3 +/- 12.2 fmol mg-1 protein), but in the longitudinal muscle 6-7 fold more binding sites (295 +/- 70 fmol mg-1 protein) were identified. 3. Inhibition studies using DPCPX (0.1-100 nM), N6-cyclopentyladenosine (CPA) (0.1-100 nM), 5'-N ethylcarboxamidoadenosine (NECA) (2 nM-10 microM) and (R)-N6 phenylisopropyladenosine (R-PIA) (1 nM-1 microM) to displace the binding of [3H] DPCPX at a concentration around the Kd value (1 nM), demonstrated an order of potency of displacement in all tissues of DPCPX > or = CPA > R-PIA > NECA. This potency order is characteristic of an A1 receptor, indicating that [3H]-DPCPX binds to adenosine A1 receptors in the rat duodenum, colon and vasa deferentia. Two site analysis revealed that the agonists bind to both a high and low affinity state of the receptor.4. The existence of Al binding sites in the rat vasa deferentia, colon muscularis mucosae and duodenum, and their absence in the urinary bladder, is consistent with previous functional studies.However, in contrast to the findings of the [3H]-DPCPX binding assay, no functional response mediated by adenosine Al receptors could be detected by measuring contractile or relaxant responses to CPA in the colon longitudinal muscle. The functional significance of the binding sites in this tissue has therefore yet to be determined. PMID- 7889281 TI - Block of endothelin-1-induced release of thromboxane A2 from the guinea pig lung and nitric oxide from the rabbit kidney by a selective ETB receptor antagonist, BQ-788. AB - 1. The present study characterizes the receptors responsible for endothelin-1 induced release of thromboxane A2 from the guinea pig lung and of endothelium derived nitric oxide from the rabbit perfused kidney, by the use of the selective ETA receptor antagonist, BQ-123, and a novel selective ETB receptor antagonist, BQ-788. 2. In the guinea pig perfused lung, endothelin-1 (ET-1) (5 nM) induced a marked increase of thromboxane A2 which was reduced by 17 +/- 5.0, 70 +/- 1.0 and 93 +/- 1.2% by BQ-788 infused at concentrations of 1, 5 and 10 nM respectively. In contrast, BQ-123 (0.1 and 1.0 microM) had little or no effect on the ET-1 induced release of thromboxane A2. 3. In the same perfused model, the selective ETB agonist, IRL 1620 (50 nM), stimulated the release of thromboxane A2, but not prostacyclin. The eicosanoid-releasing properties of IRL 1620 were abolished by BQ-788 at 10 nM, yet were unaffected by BQ-123 (1 microM). 4. In the rabbit perfused kidney, BQ-788 (10 nM) potentiated the increase of perfusion pressure induced by endothelin-1 (1, 5 and 10 nM) by approximately 90%, but not that induced by angiotensin II (1 microM). Furthermore, the selective ETB receptor antagonist did not reduce the release of prostacyclin triggered by either peptide. 5. In another series of experiments, pretreatment of the perfused kidney with a nitric oxide synthase inhibitor, L-NAME (100 microM), potentiated the pressor responses to both endothelin-1 and angiotensin II. Under L-NAME treatment, BQ-788 did not further potentiate the pressor response to endothelin 1. 6 Our results illustrate the predominant role of ETB receptor activation in the release of thromboxane A2 and nitric oxide triggered by endothelin-l in the guinea pig perfused lung and rabbit kidney respectively. PMID- 7889282 TI - Interactions of chloroethylclonidine with rauwolscine- and prazosin-sensitive adrenoceptors in dog saphenous vein. AB - 1. alpha 1-Adrenoceptors have been classified pharmacologically into four subtypes (alpha 1A, alpha 1B, alpha 1C and alpha 1D) on the basis of their differential affinity for novel antagonists such as chloroethylclonidine (CEC). While CEC is considered an alpha 1B-adrenoceptor antagonist, our earlier studies revealed that it also acted like an agonist in the dog saphenous vein (DSV). The present study characterized the contraction induced by CEC in endothelium-denuded rings from DSV. 2. Concentration-response curves for CEC were constructed in the absence (EC50 value of 11.13 +/- 3.6 microM, n = 8) and presence of propranolol (beta-adrenoceptor antagonist, 30 nM), rauwolscine (alpha 2-adrenoceptor antagonist, 30 nM), prazosin (alpha 1-adrenoceptor antagonist, 30 nM) or methysergide (5HT2 antagonist, 30 nM) or both prazosin and rauwolscine. Pretreatment with methysergide (9.83 +/- 5.14 microM, n = 4) or propranolol (23.78 +/- 12.32 microM, n = 4) had no consistent effect. In the presence of rauwolscine, the concentration-response curve for CEC was significantly shifted to the right with an EC50 value of 48.82 +/- 13.2 microM (n = 8). In the presence of prazosin, the CEC concentration-response curve had an EC50 value of 29.12 +/- 6.42 microM (n = 8). Pretreatment with both prazosin and rauwolscine shifted the concentration-response curve for CEC to the right with an EC50 value of 72.67 +/- 10.69 microM (n = 8, P < 0.05). Maximum responses were significantly reduced only in tissues that were treated with both prazosin and rauwolscine. 3. CEC (100 microM) pretreatment abolished prazosin binding sites and reduced the Bmax for rauwolscine by 50% without affecting the Kd value or the Hill slope.4. In Ca2+ free Krebs solution containing 50 microM EGTA, CEC produced a small transient contraction,suggesting that it can mobilize internally-stored Ca2+ . Pretreatment with rauwolscine abolished the CEC-induced contraction in Ca2+-free medium; prazosin pretreatment reduced but did not abolish CEC response in Ca2+-free medium.5. Restoring Ca2+ (0.5-2.5 mM) to the extracellular solution increased CEC contraction in a concentration-dependent manner, reaching a plateau at around 1.5mM Ca2 . The contraction was insensitive to nicardipine (1 microM), a voltage operated Ca2+ channel blocker, but was blocked in a concentration-dependent manner by the putative receptor-operated Ca2+ channel blockers, SK&F 96365(1-1O microM) and genistein, also a tyrosine kinase inhibitor (10-100 microM).6. We conclude that CEC acts on rauwolscine- and, to a less extent, prazosin-sensitive adrenoceptors inDSV to release internally stored Ca2+ and to open receptor operated Ca2+ channels. The inhibitory effect on CEC-induced contraction that depended on external Ca2+ by genistein suggests a role forty rosine kinase in the regulation of dihydropyridine-insensitive Ca2+ entry. PMID- 7889283 TI - Effect of type A and B monoamine oxidase selective inhibition by Ro 41-1049 and Ro 19-6327 on dopamine outflow in rat kidney slices. AB - 1. The influence of pargyline and of selective inhibitors of type A and B monoamine oxidase (MAO), Ro 41-1049 and Ro 19-6327 respectively, on the outflow of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxyphenylalanine (L-DOPA) was examined. Dopamine and DOPAC in the tissues and in the effluent were assayed by means of h.p.l.c. with electrochemical detection. 2. The levels of newly-formed dopamine and DOPAC in the perifusate decreased progressively with time. In control conditions, DOPAC/dopamine ratios in the perifusate were 3 to 5 fold those in the tissue and were found to increase progressively with time. The addition of pargyline (100 microM), produced a marked decrease in the outflow levels of DOPAC (45 to 54% reduction) and significantly increased the levels of dopamine in the effluent (102 to 158% increase); DOPAC/dopamine ratios in the perifusate remained stable throughout the perifusion and were similar to those found in the tissues. The addition of the MAO-A inhibitor Ro 41-1049 to the perifusion fluid also significantly decreased DOPAC outflow (41% to 54% reduction) and increased dopamine outflow (19% to 80% increase). In the presence of Ro 41-1049 DOPAC/dopamine ratios in the perifusate were lower (P < 0.01) than in controls; in contrast with the effect of pargyline, this ratio was found to increase (P < 0.01) throughout the perifusion period. Ro 19-6327 did not reduce the outflow of DOPAC, but significantly increased (by 40-60%) that of dopamine. In the presence of Ro 19-6237, the proportion of DOPAC to dopamine in the perifusate was similar to that of controls and significantly increased throughout the perifusion; however, this increase was less than that observed in the control group.3. When benserazide (50 microM) was added to the perifusion fluid, the levels of both dopamine and DOPAC in the effluent were similar to those observed in the absence of benserazide. However, in the presence of benserazide, DOPAC/dopamine ratios in the perifusate did not increase with time. In conditions of decarboxylase inhibition, the effects of pargyline, Ro 41-1049 and Ro 19-6327 on dopamine and DOPAC outflow were less pronounced than in experiments conducted in the absence of benserazide.4. In conclusion, the results presented here show that the fraction of newly-formed dopamine which leaves the compartment where the synthesis has occurred is a constant source for deamination into DOPAC. The results provide evidence favouring the view that MAO-A is the main form of the enzyme involved in this process; however, the data described here suggest that dopamine would also have access to MAO-B. PMID- 7889284 TI - Voltage- and time-dependent inhibitory effects on rat aortic and porcine coronary artery contraction induced by propafenone and quinidine. AB - 1. Class I antiarrhythmic drugs (e.g. Na+ channel blockers) such as propafenone and quinidine also inhibit voltage-gated Ca2+ and K+ channels. In the present paper the voltage- and time-dependent inhibitory effects of propafenone and quinidine were studied on depolarization-induced vascular contractions and 45Ca2+ uptake in isolated endothelium denuded rat aorta and pig left descending coronary artery. 2. Quinidine and propafenone (10(-7) M -5 x 10(-5) M) produced a concentration-dependent relaxation of the contractions induced by 80 mM KCl. Propafenone was significantly more potent (P < 0.05) than quinidine in both rat aorta and pig coronary arteries but both drugs more potent (P < 0.05) in relaxing rat aorta than pig coronary arteries. In rat aortic rings, the relaxant effects of propafenone were unaffected by pretreatment with the Na+ channel blocker, tetrodotoxin. 3. The degree of inhibition produced after prolonged exposure (40 min) to propafenone and quinidine differed as the time of depolarization with 80 mM KCl was increased. Quinidine (3 x 10(-6) M, 10(-5) M and 3 x 10(-5) M) not only produced an inhibition at the very early stage of contraction, but also a time-dependent inhibition was observed. In contrast, propafenone (10(-6) M, 3 x 10(-6) M and 10(-5) M) produced a more marked concentration-dependent early block but only a mild time-dependent inhibition.4. The voltage-dependence of propafenone- and quinidine-induced inhibition, was studied in rat aorta and coronary arteries which had been incubated in 5 or 40mM KCl Ca2+-free solution and then contracted by changing the bath solution to 100 mM KCI and 2 mM CaCl2 solution. The inhibitor effects of quinidine were significantly enhanced (P <0.05) when the preparations were preincubated in 40 mMKCl (depolarizing) solution. In contrast, the effects of propafenone were quite similar in 5 or in 40 mMKCI solution.5. Quinidine, 10-5 M, produced a greater inhibition (P<0.05) of 100 mM KCl-stimulated 45Ca2+ uptake in aortic rings preincubated in depolarizing as compared to normal solution. In contrast, the inhibition produced by 3 x 10-6 M propafenone was similar in aortic rings incubated in 5 or 40 mM KCl solution.6.It is concluded that both quinidine and propafenone inhibited vascular smooth muscle contraction which could be attributed to reduced Ca2+ entry. The voltage- and time-dependent inhibitory effects of quinidine may reflect an increased binding of the drug to Ca2+ channels at depolarized potentials. PMID- 7889285 TI - The role of myoendothelial cell contact in non-nitric oxide-, non-prostanoid mediated endothelium-dependent relaxation of porcine coronary artery. AB - 1. Experiments were designed to analyse the requirement of myoendothelial junctions by bradykinin-induced endothelium-dependent relaxations resistant to NG nitro-L-arginine (L-NOARG) and indomethacin porcine coronary arteries. 2. Rings of porcine coronary arteries were contracted with the thromboxane receptor agonist, U46619 and relaxations to bradykinin recorded isometrically. All experiments were performed in the presence of indomethacin. Nitric oxide (NO) mediated effects were blocked by the NO synthase inhibitor L-NOARG (250 microM) and myoendothelial contacts inhibited by treatment with hypertonic solution containing D-mannitol or sucrose (each 180 mM) or the gap junctional uncoupling agent 1-heptanol (2 mM). High [K+] solutions (40 mM) were used to probe a possible contribution of endothelium-derived hyperpolarizing factor (EDHF). 3. In the presence of endothelium, bradykinin induced concentration-dependent relaxations with a mean EC50 of 3.2 nM and a maximum response of 95 +/- 1% of papaverine-induced relaxation (control curve). 4. In the absence of endothelium, bradykinin failed to induce relaxations. Addition of cultured porcine aortic endothelial cells to the organ bath resulted in some relaxation and restored in part the relaxant effect of bradykinin. This endothelial cell-mediated relaxant effect was completely abolished in the presence of 250 microM L-NOARG. 5. Bradykinin-induced relaxations in endothelium-preserved rings were only slightly suppressed by L-NOARG (86% of control). In vessels partially depolarized by high extracellular [K+] (40 mM) relaxation was reduced to 72% of control. In the presence of L-NOARG, bradykinin failed to relax partially depolarized vessels. 6. In the presence of 2 mM -heptanol, 180 mM mannitol or 180 mM sucrose maximum relaxation to bradykinin was reduced to ~70%, i.e. to the same extent as in the presence of high [K+]. The remaining relaxation was sensitive to blockade by L NOARG.7. Tissue cyclic GMP content which reflects NO activity, was increased about 4 fold by bradykinin(300 nM). This increase was unaffected by high [K+], heptanol or sucrose but blocked by L-NOARG.8 Our results suggest that non-nitric oxide- and non-prostanoid-mediated endothelium-dependent relaxation of porcine coronary artery requires functionally intact myoendothelial junctions. PMID- 7889286 TI - The effects of beta-adrenoceptor stimulation on adhesion of human natural killer cells to cultured endothelium. AB - 1. The circulation of natural killer (NK) cells in vivo is influenced by physical exercise, mental stress, and infusion of beta-adrenoceptor agonists. We have previously presented in vitro data, showing that beta 2-adrenoceptor agonists induce detachment of NK cells from endothelial cells (EC), supporting the hypothesis that NK cells can be recruited from the marginating pool in blood vessels. 2. Because NK cells as well as EC express beta 2-adrenoceptors, the present study was conducted to investigate whether stimulation of the beta adrenoceptors on NK cells, EC or both cell types is required to induce detachment from EC. 3. Cells were pretreated (15 min) with a selective beta 2-adrenoceptor antagonist, GR81706, at various concentrations. The duration of beta-adrenoceptor blockade was tested by determining the adenosine 3',5'-cyclic monophosphate (cyclic AMP) production induced by terbutaline (a beta 2-adrenoceptor specific agonist). This receptor-mediated response was effectively inhibited for at least 4 h, whereas the cyclic AMP production in response to forskolin (a direct activator of adenylate-cyclase) was not affected. 4. Functional adhesion assays were then performed to determine the role of beta-adrenoceptors on the different cell types involved (NK and EC) in catecholamine-induced detachment. Peripheral blood mononuclear cells were allowed to adhere for 1 h to monolayers of unstimulated EC in the presence or absence of cyclic AMP inducing agents, and the percentage of NK cells in the adhering lymphocyte fraction was determined by flow cytometry. 5. Both adrenaline (10(-5) M) and forskolin (10(-5) M) caused detachment of NK cells from EC. After blockade of the P2-adrenoceptors on NK cells by pretreatment with GR81706 (10-6 M), the effect of adrenaline on NK cells adhesion was pretented; after blockade of the beta2-adrenoceptors on EC, NK cell adhesion was still significantly reduced by adrenaline. In all cases, forskolin caused detachment of NKcells.6. To establish further that stimulation of beta adrenoceptors on NK cells is sufficient to cause detachment,we showed that adrenaline also reduced adhesion of NK cells to monolayers of Chinese hamster ovary cells, which do not express beta-adrenoceptors.7. Together, these results show that stimulation of beta2-adrenoceptors on NK cells negatively influences their capacity to adhere to EC, and that beta2-adrenoceptors on EC play a negligible role in this phenomenon. PMID- 7889287 TI - A pharmacological profile of the novel, peripherally-selective kappa-opioid receptor agonist, EMD 61753. AB - 1. The pharmacological properties of the novel diarylacetamide kappa-opioid receptor agonist, EMD 61753, have been compared with those of ICI 197067 (a centrally-acting kappa agonist) and ICI 204448 (a peripherally-selective kappa agonist). 2. EMD 61753 binds with high affinity (IC50 5.6 nM) and selectivity (kappa:mu:delta:sigma binding ratio 1:536:125: > 1,786) to kappa-opioid receptors and is a full and potent (IC50 54.5 nM) agonist in an in vitro assay for kappa opioid receptors (rabbit vas deferens preparation). 3. Systemically-applied [14C] EMD 61753 is found in high concentrations in the lungs, liver, adrenal glands and kidneys. Considerably less radioactivity is detected in the whole brain, and this radioactivity is concentrated in the region of the cerebral ventricles in the choroid plexuses. EMD 61753 penetrates only poorly into the CNS. 4. EMD 61753 was weakly effective in pharmacological tests of central activity. This compound reversed haloperidolol-induced DOPA accumulation in the nucleus accumbens of the rat only at a dose of 30 mg kg-1, s.c., (doses of 0.1, 1.0 and 10 mg kg-1, s.c., and 1.0, 10 and 100 mg kg-1, p.o., were inactive). Hexobarbitone-induced sleeping in mice was prolonged by EMD 61753 at threshold doses of 10 mg kg-1, s.c., and 100 mg kg-1, p.o., whereas the motor performance of rats in the rotarod test was impaired by EMD 61753 with an ID50 value of 453 mg kg-1, s.c. 5. EMD 61753 produced dose-dependent, naloxone-reversible antinociception in the mouse formalin test (1st phase ID50 1.9 mg kg-1, s.c., and 10.4 mg kg-1, p.o.; 2nd phase ID50 0.26 mg kg-1, s.c., and 3.5 mg kg-1, p.o.) and rodent abdominal constriction test (ID50 mouse 1.75 mg kg-1, s.c., and 8.4 mg kg-1, p.o.; ID50 rat 3.2 mg kg-1, s.c., and 250 mg kg-1, p.o.). EMD 61753 was inactive, or only weakly effective, in the rat pressure test under normalgesic conditions. After the induction of hyperalgesia with carrageenin, however, this compound elicited potent, dose-dependent (ID50 0.08 mg kg-1, s.c., and 6.9 mg kg-1, p.o., after remedial application, and 0.2 mg kg-1, s.c., and 3.1 mg kg-1, p.o., after prophylactic application) and naloxone-reversible antinociception. The antinociceptive action of systemically-applied (50 mg kg-1, p.o.) EMD 61753 in the hyperalgesic pressure test was completely inhibited by injection of the K opioid antagonist norbinaltorphimine (100 Lg) into the inflamed tissue, a result which indicates that this opioid effect is mediated peripherally.6. Cutaneous plasma protein extravasation produced by antidromic electrical stimulation of the rat saphenous nerve was dose-dependently inhibited by systemically-applied EMD 61753 (ID13 values 3.7 mg kg-1, s.c., and 35.8 mg kg-1, p.o.), and this effect was completely antagonized by intraplantar application of norbinaltorphimine (50 microg). Extravasation elicited by the intraplantar application of substance P (10 microg) was not influenced by the administration of EMD 61753.7. EMD 61753 produced dose-dependent diuresis in non-hydrated rats at doses of and above 1.0 mg kg-1, s.c., and 10 mg kg-1, p.o., and in saline-loaded rats at doses of and above 10 mg kg-1, s.c.,and 30mgkg-1, p.o.8. The prostaglandin-mediated fall in mean arterial blood pressure elicited in anaesthetized rats by i.v.application of arachidonic acid was not inhibited by prior treatment with EMD 61753 (10mg kg 1,p.o.). Thus, a blockade of prostaglandin synthesis via inhibition of cyclo oxygenase activity does not contribute to the in vivo effects of EMD 61753 and its metabolites.9 The present experiments therefore indicate that EMD 61753 is a potent, selective and orally-effective full ic-opioid receptor agonist which has a limited ability to penetrate the blood-brain barrier and elicit centrally mediated sedation, putative aversion, diuresis, and antinociception. The inhibitory actions of systemically-applied EMD 61753 against hyperalgesic pressure nociception and neurogenic inflammation are mediated peripherally, probably by opioid receptors on the endings of sensory nerve fibres. PMID- 7889288 TI - The interaction of alpha-human atrial natriuretic peptide (ANP) with salbutamol, sodium nitroprusside and isosorbide dinitrate in human bronchial smooth muscle. AB - 1. Contractions in human bronchial rings evoked by methacholine (10(-6) M) were reversed by single contractions of alpha-human atrial natriuretic peptide (10(-6) M), salbutamol (10(-6) M), sodium nitroprusside (10(-6) M) or isosorbide dinitrate (4.2 x 10(-5) M) and the extent of the relaxations compared. The activity of combinations of ANP with salbutamol, sodium nitroprusside and isosorbide dinitrate were compared with those for each agonist alone. 2. ANP and salbutamol were equipotent in reversing methacholine-evoked contraction and, in combination these agonists evoked an additive response. ANP and sodium nitroprusside also evoked similar degrees of relaxation and were additive, as were ANP and isosorbide dinitrate; however, with isosorbide dinitrate a higher concentration was required to evoke the same degree of relaxation as ANP, sodium nitroprusside or salbutamol. 3. Cumulative concentration-response curves to methacholine (10(-9)-3 x 10(-4) M) were examined in the presence and absence of the above bronchodilator substances, alone and in combination allowing their abilities to protect against contraction to be compared. ANP (10(-6) M) and salbutamol (10(-6) M) each attenuated subsequent contractions evoked by methacholine, an ability not shared with sodium nitroprusside (10(-6) M) or isosorbide dinitrate (4.2 x 10(-5) M). Indeed at lower concentrations of methacholine (< 3 x 10(-7) M), sodium nitroprusside evoked a paradoxical enhancement of methacholine-evoked contractions. 4. In combination, ANP and salbutamol attenuated contractions evoked by methacholine to a significantly greater degree than that seen with either agonist alone, whilst a combination of ANP and sodium nitroprusside evoked no greater effect than that seen with ANP alone. By contrast, isosorbide dinitrate and ANP together evoked a greater inhibition than ANP alone.5 These results suggest that a combination of agents such as ANP and salbutamol evokes a greater effect than either alone, both in reversing and protecting against methacholine-evoked contractions.Such combinations may be of benefit in the treatment of patients, allowing lower doses of drug to be used. Combinations of ANP and isosorbide dinitrate may likewise be of interest; however, the mechanism underlying the enhancement of ANP responses by isosorbide dinitrate requires further study. PMID- 7889289 TI - Prevention of thrombosis and rethrombosis and enhancement of the thrombolytic actions of recombinant tissue-type plasminogen activator in the canine heart by DMP728, a glycoprotein IIb/IIIa antagonist. AB - 1. We studied DMP728, a non-peptide glycoprotein (GP) IIb/IIIa receptor antagonist, for prevention of coronary artery thrombosis or rethrombosis in a chronic canine model subjected to arterial injury. 2. In protocol I, DMP728 (1.0 mg kg-1, i.v., n = 8) or saline (n = 8) was administered and a 150 microA anodal current was applied to the intimal surface of the left circumflex coronary artery (LCX). Dogs were monitored for 6 h and again on each of 5 subsequent days. 3. Ex vivo platelet aggregation was inhibited but returned to baseline 1 day after drug administration. Thrombus weight was reduced (saline, 20.7 +/- 5.0 mg; DMP728 1.7 +/- 0.4 mg; P < 0.05), as was infarct size [saline, 27.5 +/- 4.3; DMP728, 1.6 +/- 0.7 (per cent left ventricle); P < 0.05]. All control animals died by day 3, while all but one of the treated dogs survived the entire protocol (P < 0.05). 4. In protocol II, an LCX thrombus was induced and thrombolytic therapy was initiated 30 min later. DMP728 (1.0 mg kg-1, i.v., n = 8) or saline (n = 8) was administered 5 min after recombinant tissue-type plasminogen activator infusion had begun. The incidence of reocclusion was reduced by DMP728 (saline, 4/8; DMP728, 1/8). One day after thrombolysis, 7/8 DMP728-treated animals were alive compared with 1/8 in the control group (P = 0.01). 5. DMP728 inhibited ex vivo platelet aggregation, prevented primary and secondary occlusive thrombus formation, reduced thrombus weight and infarct size and increased survival in a chronic canine model of coronary artery thrombus formation. DMP728 is an effective anti-platelet intervention when used as the singular adjunctive agent in association with thrombolytic therapy. PMID- 7889290 TI - Peripheral and central sites of action of GABA-B agonists to inhibit the cough reflex in the cat and guinea pig. AB - 1. The GABA-B receptor agonists baclofen and 3-aminopropylphosphinic acid (3 APPi) have antitussive activity in the cat and guinea pig. The purpose of this study was to investigate the sites of action of these GABA-B receptor agonists to inhibit the cough reflex. 2. Single intracerebroventricular (i.c.v.) cannulas were placed in the lateral ventricles of anaesthetized guinea pigs. Approximately 1 week later, the animals were exposed to aerosols of capsaicin (0.3 mM) to elicit coughing. Coughs were detected with a microphone and counted. 3. Cough was produced in anaesthetized cats by mechanical stimulation of the intrathoracic trachea and was recorded from electromyograms of respiratory muscle activity. Cannulas were placed for intravenous (i.v.) or, in separate groups of animals, intravertebral arterial (i.a.) administration of baclofen, 3-APPi, the centrally active antitussive drug codeine or the peripherally active antitussive drug BW443c. Dose-response relationships for i.v. and i.a. administration of each drug were generated to determine a ratio of i.v. ED50 to i.a. ED50, known as the effective dose ratio (EDR). The EDR will be 20 or greater for a centrally acting drug. 4. In the guinea pig, baclofen (3 mg kg-1, s.c.) and 3-APPi (10 mg kg-1, s.c.) inhibited capsaicin-induced cough by 50% and 35% respectively. The antitussive activity of baclofen was completely blocked by i.c.v. administration of the GABA-B receptor antagonist CGP 35348 (10 micrograms). Conversely, the antitussive effect of 3-APPi was unaffected by i.c.v. CGP 35348. However, systemic administration of CGP 35348 (30 mg kg-1, s.c.) completely blocked the antitussive activity of 3-APPi (10 mg kg-1, s.c.). In separate experiments baclofen alone (1 microg, i.c.v.) inhibited capsaicin-induced cough by 78%. 3 APPi (10 and 100 microg, i.c.v.) had no effect on capsaicin-induced cough in the guinea pig.5. In the cat, potencies (ED50) of the standards and GABA-B agonists by the i.v. route were: codeine(0.34 mg kg-1), BW443C (0.17 mg kg-1), baclofen (0.63 mg kg-1) and 3-APPi (2.3 mg kg-1). Potencies of these drugs by the i.a. route were: codeine, 0.013 mg kg-1; BW443C, 0.06mg kg-1; baclofen,0.016mg kg-1; and 3-APPi, 0.87 mg kg-1. The EDRs for each drug were: codeine, 26; BW443C, 3;baclofen, 39; and 3-APPi, 3.6 We conclude that in both the cat and guinea pig baclofen inhibits cough by a central site of action,while 3-APPi inhibits cough by a peripheral site of action. PMID- 7889291 TI - Effects of the non-NMDA antagonists NBQX and the 2,3-benzodiazepine GYKI 52466 on different seizure types in mice: comparison with diazepam and interactions with flumazenil. AB - 1. GYKI 52466 is a benzodiazepine derivative that has muscle relaxant and anticonvulsant properties thought to be mediated by highly selective, noncompetitive antagonism of non-NMDA receptors. However, recent electrophysiological data showed that, in addition to non-NMDA receptors, the GABAA-receptor associated benzodiazepine site is involved in the depressant effect of GYKI 52466 on spinal reflex transmission. In view of the structural similarities between the 2,3 benzodiazepine derivative GYKI 52466 and 1,4 benzodiazepines such as diazepam, the benzodiazepine site of GABAA receptor complex could also be involved in the anticonvulsant activity of GYKI 52466, which has not yet been proven. This prompted us to study the effect of the benzodiazepine receptor antagonist, flumazenil, on anticonvulsant and adverse effects of GYKI 52466 in different seizure models in mice. The non-NMDA antagonist, NBQX and diazepam were used for comparison. 2. Seizure threshold models for different types of generalized seizures were used. The threshold for maximal (tonic) electroshock seizures (MES) was significantly increased by GYKI 52466 (10-20 mg kg-1), NBQX (80-120 mg kg-1) and diazepam (5 mg kg-1) shortly after i.p. drug administration. The same dose-range of the non-NMDA antagonists also significantly increased the threshold for myoclonic and clonic seizures induced by i.v. infusion of pentylenetetrazol (PTZ), although the magnitude of threshold increases obtained with the respective drugs, differed, at least in part, from that seen in the MES experiments. GYKI 52466 was clearly less potent in increasing PTZ thresholds for myoclonic and clonic seizures than on the MES threshold, while NBQX exerted about the same potency in both models. In contrast to the non-NMDA antagonists, diazepam was capable of increasing themyoclonic and clonic PTZ seizure threshold at much lower doses than the MES threshold. The PTZ threshold for tonic seizures was markedly increased by GYKI 52466, while NBQX and diazepam were clearly less potent in this respect.3. With respect to adverse effects, GYKI 52466 and NBQX induced significant seizure threshold increases in the different seizure models only at doses which caused sedation and ataxia, while diazepam increased the myoclonic and clonic PTZ seizure threshold at doses below those inducing motor impairment.4. Flumazenil (5-20 mg kg-1) antagonized the anticonvulsant and adverse effects of diazepam but not GYKI 52466. Instead, the anticonvulsant effect of GYKI 52466 was potentiated by flumazenil in some experiments. The anticonvulsant activity of NBQX was slightly reduced by flumazenil in the MES model but not in the PTZ test.5. The data indicate that the GABAA receptor-associated benzodiazepine site is not critically involved in anticonvulsant or adverse effects of GYKI 52466. However, both GYKI 52466 and NBQX were unable to increase seizure thresholds at doses below those inducing sedation and motor impairment,thus demonstrating that non-NMDA antagonists lack a selective anticonvulsant action in standard models of generalized seizures. PMID- 7889292 TI - Inhibitory 5-hydroxytryptamine receptors involved in pressor effects obtained by stimulation of sympathetic outflow from spinal cord in pithed rats. AB - 1. A study was made of the effects of 5-hydroxytryptamine (5-HT) on pressor response induced in vivo by electrical stimulation of the sympathetic outflow from the spinal cord of pithed rats. All animals had been pretreated with atropine. Intravenous infusion of 5-hydroxytryptamine at doses of 10 and 20 micrograms kg-1 min-1 reduced the pressor effects obtained by electrical stimulation at intervals of 10 min over the 1 h of infusion. 2. This inhibitory action of 5-HT was depressed by cyproheptadine and methiothepin but was not modified by ketanserin or MDL-72222. By contrast, the inhibitory action of 5-HT was lost in pithed rats that had been pretreated with exogenous noradrenaline. 3. The 5-HT1 receptor agonist 5-carboxamidotryptamine (5-CT) caused an inhibition of the pressor response, whereas the 5-HT3 receptor agonist, 1-phenylbiguanide, produced a variable but significant increase in the pressor response. The 5-HT2 receptor agonist, m-CPP, did not modify the pressor sympathetic response. 4. Our results suggest that 5-hydroxytryptamine interferes with sympathetic neurotransmission by inhibiting pressor effects as a result of stimulation of the complete sympathetic outflow, and that this inhibition is mainly through a presynaptic 5-HT1 mechanism. PMID- 7889293 TI - Studies on the mechanisms involved in the inflammatory response in a reversed passive Arthus reaction in guinea-pig skin: contribution of neutrophils and endogenous mediators. AB - 1. Mediators of inflammation can increase vascular permeability in at least two different ways: by acting directly on endothelial cells or, indirectly, through an incompletely understood mechanism, dependent on circulating neutrophils. Neutrophil-dependent oedema formation has been described in the skin of rabbits, rats, hamsters, mice and man. In contrast, we presented evidence in a previous study that local oedema formation induced by i.d. injection of chemoattractants in guinea-pig skin was neutrophil-independent. In the present study, we sought evidence of neutrophil-dependent oedema formation in immune-complex-mediated vasculitis, the reversed passive Arthus (RPA) reaction, in guinea-pig skin. We also investigated whether haemorrhage in the RPA reaction was neutrophil dependent (as it is in other species) and the role of endogenous mediators of inflammation (prostaglandins, nitric oxide, histamine, PAF and leukotrienes) in contributing to the local inflammatory response. 2. In the RPA reaction, most oedema formation occurred over the first 60 min whereas 111In-neutrophil accumulation was still increasing from 60 to 240 min. The different kinetics of these two events suggested that they may be dissociated. 3. Oedema formation was partially inhibited by a long-acting PAF antagonist (UK-74,505) and an H1 histamine receptor antagonist (mepyramine) but not by a 5-lipoxygenase inhibitor (ZM 230487). A nitric oxide synthesis inhibitor (NG-nitro-L-arginine methyl ester, L-NAME) suppressed oedema formation by 68% whereas a cyclo-oxygenase inhibitor suppressed oedema by 27%. 4. 111In-neutrophil accumulation in the RPA reaction was partially suppressed by UK-74,505. In contrast, ZM 230487 was without effect at doses which abrogated arachidonic acid-induced 111In-neutrophil accumulation. 5. The anti-CD18 monoclonal antibody, (mAb) 6.5E F(ab')2, effectively inhibited 111In-neutrophil accumulation induced by PAF, zymosan activated plasma (ZAP) and in the RPA reaction. However, oedema formation measured in the same sites was not altered. In contrast, oedema formation in the RPA reaction was partially suppressed by 6.5E whole mAb which was 2.5 times more potent than 6.5EF(ab')2 at inhibiting guinea-pig neutrophil adhesion to protein coated plastic. Haemorrhage induced by PAF and in the RPA reaction was significantly inhibited by 6.5E F(ab')2 pretreatment.6. We conclude that in the RPA reaction in guinea-pig skin, oedema formation is partially neutrophil dependent as assessed by using an anti-CD18 mAb, whereas ZAP-induced oedema formation is neutrophil-independent. Haemorrhage was also dependent on neutrophil accumulation. In addition, our studies support a role for PAF in mediating both oedema formation and "'In-neutrophil accumulation in the RPA reaction. Endogenous release of histamine also appears to be important in mediating oedema formation suggesting that mast cells play a critical role in increases of vascular permeability in inflammatory reactions in guinea-pig skin. Moreover, our results confirm previous findings which suggest a dominant role for nitric oxide in maintaining cutaneous blood flow in the guinea-pig. PMID- 7889294 TI - Modulation of morphine antinociception in the mouse by endogenous nitric oxide. AB - 1. L-Arginine (100-1000 mg kg-1) administered orally (p.o.) or intraperitoneally (i.p.), but not intracerebroventricularly (i.c.v., 0.08 mg per mouse), reduced the antinociceptive effect of morphine (0.5-10 mg kg-1 s.c.) assessed in mice using three different tests: hot plate, tail-flick and acetic acid-induced writhing. D-Arginine (up to 1000 mg kg-1 p.o. or i.p.) was ineffective. 2. NG Monomethyl-L-arginine (L-NMMA, 5-50 mg kg-1 i.p.) and NG-nitro-L-arginine methyl ester (L-NAME, 5- 30 mg kg-1 i.p.), but not NG-nitro-D-arginine methyl ester (D NAME, 30 mg kg-1 i.p.), reversed in all assays the effect of L-arginine on morphine-induced antinociception. 3. Morphine (10 mg kg-1 s.c.), L-arginine (1000 mg kg-1 p.o.) or L-NAME (30 mg kg-1 i.p.), either alone or in combination, did not produce changes in locomotor activity or sensorimotor performance of animals. 4. These results suggest that the L-arginine-nitric oxide pathway plays a modulating role in the morphine-sensitive nociceptive processes. PMID- 7889295 TI - Mechanism of the cardiovascular activity of laudanosine: comparison with papaverine and other benzylisoquinolines. AB - 1. The activity of (+/-)-laudanosine, a benzyltetrahydroisoquinoline alkaloid, was investigated in pithed rats and rat isolated aorta. Its effects on [3H]-(+) cis-diltiazem and [3H]-nitrendipine binding to rat cerebral cortical membranes, and on the different molecular forms of cyclic nucleotide phosphodiesterases (PDE) isolated from bovine aorta were investigated. 2. The dose-response curve to methoxamine (3-300 micrograms kg-1, i.v.) in normotensive pithed rats was shifted to the right by (+/-)-laudanosine, 3 and 6 mg kg-1. 3. (+/-)-Laudanosine inhibited in a concentration-dependent manner the contractile responses evoked by noradrenaline (NA 1 microM), depolarizing solution (KCl 80 mM) or depolarizing solution plus phentolamine (10 microM) in rat isolated aorta. The alkaloid appeared to be more potent against NA-induced contractions. 4. In Ca(2+)-free solution, (+/-)-laudanosine (100 microM) inhibited the contraction evoked by NA and did not modify the phasic contractile response evoked by caffeine. The alkaloid did not modify the refilling of the intracellular Ca(2+)-sotres sensitive to NA or caffeine. 5. (+/-)-Laudanosine inhibited [3H]-prazosin binding to cortical membranes and also inhibited [3H]-(+)-cis-diltiazem but with a lower potency. [3H]-nitrendipine binding was not affected by laudanosine. 6. (+/-) Laudanosine does not have a significant effect on the different forms of PDEs isolated from bovine aorta. In contrast, compounds structurally related to this alkaloid such as papaverine and its derivatives, had a non-selective or more specific inhibitory effect on these PDE forms. These differences can be explained on the basis of their structural features: the planarity of the isoquinoline ring(papaverine) facilitates the interaction with receptor sites, and the different position of the benzyl group does not modify the activity unless this position leads to the presence of a chiral centre (laudanosine).7. These results suggest that (+/-)-laudanosine has a selective activity as an alpha1-adrenoceptor blocker. Its lack of action on different PDE forms provides us with information about a group of benzylisoquinolines that with small structural changes show a different effect on PDE-forms isolated from vascular smooth muscle. PMID- 7889296 TI - Characterization of the adenosine receptors mediating hypothermia in the conscious mouse. AB - 1. The effects of a range of adenosine receptor-selective ligands on body temperature were investigated following intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injection in conscious mice. The compounds tested were the non-selective adenosine receptor agonist 5'-N-ethyl-carboxamidoadenosine (NECA), the adenosine A1 receptor-selective agonists cyclopentyl-adenosine (CPA), N6-(9R phenyl-isopropyl)-adenosine (R-PIA) and N-(1S,trans)-[2-hydroxyclopentyl] adenosine (GR79236), the A2a receptor selective agonist 2-[p-(2 carboxyethyl)phenethylamino]-5'-N-ethylcarboxyamidoaden osine (CGS-21680), the A2b receptor agonist N-[(2-methylphenyl)methyl[adenosine (metrifudil) and the A3 receptor agonist N6-(4-aminophenylethyl)adenosine (APNEA). 2. NECA (0.01-1 microgram, i.c.v.), all of the A1-selective agonists (0.01-1 microgram, i.c.v.) and APNEA (0.1-3 micrograms i.c.v.) produced profound and dose-related hypothermia and sedation. However, CGS-21680 (0.1-10 micrograms i.c.v.) and metrifudil (0.01-1 microgram i.c.v.), produced only mild hypothermia at the highest doses tested. 3. The hypothermic response to the A1 receptor-selective agonists, GR79236 and R-PIA was dose-dependently antagonized by peripheral administration of either the non-selective adenosine receptor antagonist, 8 phenyltheophylline (8-PT, approximately 40 and 30 fold rightward shifts of the dose-response curves respectively at 10 mg kg-1, i.p.), or the adenosine A1 receptor-selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, approximately 20 fold shift of the GR79236 dose-response curve at 1 mg kg-1, i.p.). The hypothermic response to APNEA was similarly dose-dependently antagonized by the A1 receptor-selective antagonist, DPCPX (5 fold shift at 0.1 mg kg-1, i.p.). 4.8(p-Sulphophenyl)theophylline (8-SPT, 10 and 30 mg kg-1, i.p.), a non-selective adenosine receptorantagonist that penetrates the blood brain barrier poorly, produced only modest antagonism (approximately 2 fold shift at 30 mg kg-1, i.p.) of the hypothermic response to GR79236.5. These data suggest that hypothermia induced by adenosine analogues in the conscious mouse is mediated via adenosine A1 receptors, which are probably located in the CNS. PMID- 7889298 TI - Differential sensitivity of 3H-agonist binding to pre- and postsynaptic 5-HT1A receptors in bovine brain. AB - 1. The full and weak partial 5-HT1A agonist ligands [3H]-8-OH-DPAT and [3H]-BMY 7378 were used to characterize the binding parameters of pre- and postsynaptic 5 HT1A binding sites in bovine dorsal raphe and hippocampal membranes, respectively. The Kd and Bmax values for the individual radioligands were indistinguisable across the regions tested, as were the Ki values generated by a series of agents acting at 5-hydroxytryptamine (5-HT) receptors. 2. The concentration-dependent allosteric attenuation of [3H]-8-OH-DPAT and [3H]-BMY 7378 binding produced by the nonhydrolyzable guanyl nucleotide, Gpp(NH)p, generated similar IC50 values within a particular region; however, these were significantly different between regions. While the maximal attenuation of [3H]-8 OH-DPAT and [3H]-BMY-7378 binding was similar in dorsal raphe, Gpp(NH)p produced a significantly greater attenuation of [3H]-8-OH-DPAT binding in hippocampal membranes when compared to [3H]-BMY-7378. The maximal attenuation of [3H]-8-OH DPAT binding by Gpp(NHp) in hippocampus was also significantly greater than that seen with either radioligand in dorsal raphe. 3. Although exposure to Gpp(NH)p had no effect on the affinity constants of either radioligand in either region, it produced a concentration-dependent reduction in the maximal number of binding sites for both radioligands in both regions. While the percentage reduction in Bmax values were similar for both radioligands in the dorsal raphe, Gpp(NH)p reduced the Bmax of [3H]-8-OH-DPAT in hippocampus significantly more than that of [3H]-BMY-7378. 4. These results suggest that while pre- and postsynaptic 5-HT1A receptors may share similar pharmacological recognition properties, a region dependent difference in the coupling of the 5-HT1A receptor to G-proteins may exist. PMID- 7889297 TI - Regional effects of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine release and metabolism in the rat brain. AB - 1. The effects of single-dose regimens of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine (DA) release and metabolism were evaluated in the frontal cortex, hypothalamus, nucleus accumbens and striatum. The regimens selected are known to produce substantial behavioural effects. 2. 3 Methoxytyramine (3MT) and 3,4-dihydroxyphenylacetic acid (DOPAC) rates of formation were used to assess DA metabolism by catechol-O-methyltransferase and monoamine oxidase respectively. The rate of formation of 3MT was used as an index of synaptic DA. The ratio and sum, respectively, of 3MT and DOPAC rates of formation were used to assess DA reuptake inhibition and turnover. 3. The effects of amphetamine on 3MT production and DOPAC steady-state levels were similar in all regions, suggesting similar pharmacodynamic actions. Amphetamine increased 3MT formation and steady-state levels, and reduced DOPAC steady-state levels. DOPAC formation was significantly reduced only in the nucleus accumbens and striatum. Total DA turnover remained unchanged except in the nucleus accumbens. Apparently, the amphetamine-induced increase in DA release occurred at the expense of intraneuronal DA metabolism and did not require stimulation of synthesis. 4. Nomifensine elevated 3MT formation in all regions. A similar effect was produced by cocaine except in the nucleus accumbens. GBR 12909 elevated 3MT production only in the hypothalamus, the striatum and the nucleus accumbens. 5. Cocaine selectively reduced DOPAC formation in the frontal cortex. Nomifensine increased and reduced, respectively, DOPAC formation in striatum and hypothalamus. GBR 12909 elevated DOPAC formation in all regions except the cortex, where pargyline did not reduce DOPAC levels in GBR 12909-treated rats. 6. Ratios and sum of 3MT and DOPAC rates of formation also exhibited wide regional variations for each drug. In contrast to the other drugs, the ratio was not increased after GBR 12909. Apparently, the DA uptake properties of this drug are poorly related to its in vivo effects on the ratio of 3MTproduction to that of DOPAC, which should increase when DA reuptake is inhibited.7. Total DA turnover was increased by GBR 12909 in the hypothalamus, nucleus accumbens and striatum, while cocaine and nomifensine increased it only in the nucleus accumbens and striatum respectively.8. It is concluded that:(a) 3MT and DOPAC rates of formation provide better indices of DA release and metabolism than do their steady-state concentrations.(b) Some effects of DA uptake blockers on DA transmission, especially those of nomifensine and cocaine, may be attributed to increased DA release.(c) Patterns of regional effects of psychostimulants on the dynamics of DA release and metabolism may be better biochemical correlates of stimulant-induced behaviours than would changes in any single region. PMID- 7889299 TI - Dexamethasone-induced selective inhibition of the central mu opioid receptor: functional in vivo and in vitro evidence in rodents. AB - 1. Endogenous corticosteroids and opioids are involved in many functions of the organism, including analgesia, cerebral excitability, stress and others. Therefore, we considered it important to gain information on the functional interaction between corticosteroids and specific opioid receptor subpopulations. 2. We have found that systemic administration (i.p.) of the potent synthetic corticosteroid, dexamethasone, reduced the antinociception induced by the highly selective mu agonist, DAMGO or by less selective mu agonists morphine and beta endorphin administered i.c.v.. On the contrary dexamethasone exerted little or no influence on the antinociception induced by a delta 1 agonist, DPDPE and a delta 2 agonist deltorphin II. Dexamethasone potentiated the antinociception induced by the kappa agonist, U50,488. 3. In experiments performed in an in vitro model of cerebral excitability in the rat hippocampal slice, dexamethasone strongly prevented both the increase of the duration of the field potential recorded in CA1, and the appearance and number of additional population spikes induced by mu receptor agonists. 4. In both models pretreatment with cycloheximide, a protein synthesis inhibitor, prevented the antagonism by dexamethasone of responses to the mu opioid agonists. 5. Our data indicate that in the rodent brain there is an important functional interaction between the corticosteroid and the opioid systems at least at the mu receptor level, while delta and kappa receptors are modulated in different ways. PMID- 7889301 TI - Pharmacological analysis of ecto-ATPase inhibition: evidence for combined enzyme inhibition and receptor antagonism in P2X-purinoceptor ligands. AB - 1. Previous studies have shown that suramin and FPL 66301 are competitive antagonists at the P2X-purinoceptor in the rabbit ear artery. Those studies employed alpha,beta-methylene ATP, a poorly hydrolysable ATP analogue, as the agonist. In this study these compounds have been tested using ATP as the agonist. 2. Suramin, in the concentration range 30-1000 microM, potentiated the contractile effects of ATP, producing a 3-fold leftward shift of the ATP E/[A] curves. FPL 66301, in the concentration range 100-1000 microM, produced a significant but small (approximately 3-fold) rightward shift of the ATP curves. These results are in marked contrast with previous studies using alpha,beta methylene ATP in which 30-fold rightward shifts were achieved using the same concentration ranges of suramin and FPL 66301. 3. Suramin and FPL 66301 were tested as ecto-ATPase inhibitors in a human blood cell assay. Suramin inhibited the enzyme with a pIC50 of 4.3, FPL 66301 with a pIC50 of 3.3. 4. The pharmacological data were analysed using a theoretical model describing the action of a compound with dual enzyme inhibitory and receptor antagonistic properties on the effects of an agonist susceptible to enzymatic degradation. The model was found to fit the data well using the known pKB estimates for suramin and FPL 66301 and similar relative (but not absolute) pK1 estimates to those obtained for the compounds in the enzyme assay. 5. From this analysis it was concluded that the limited shifts of ATP E/[A] curves produced by suramin and FPL 66301 were the result of 'self-cancellation' of the potentiating (enzyme inhibitory) and rightward-shifting (receptor antagonistic) properties.6. The analysis also indicated that the presence of ecto-ATPase activity in the rabbit ear artery preparation has a marked effect on the apparent potency of ATP. The experimental p[A50] was 3.4,whereas the 'true' value, that is the value which would be obtained in the absence of ecto-ATPase activity, was 6.0, some 400-fold higher.7 Two conclusions are drawn from this study. Firstly, caution must be exercised in the use of suramin and FPL 66301 as tools for receptor classification. Absence of overt antagonism by these compounds when metabolically unstable agonists are used could lead to erroneous claims for receptor subtypes.Secondly, the agonist potency order currently used to designate P2X- purinoceptors may require modification. PMID- 7889300 TI - Anti-inflammatory and bronchodilator properties of RP 73401, a novel and selective phosphodiesterase type IV inhibitor. AB - 1. We have investigated the effects of RP 73401, a novel, potent and highly selective cyclic nucleotide phosphodiesterase (PDE) type IV inhibitor, in guinea pig and rat models of bronchoconstriction and allergic inflammation. In some models, the effects of RP 73401 have been compared with those of the standard PDE type IV inhibitor, rolipram. 2. RP 73401 (0.4-400 micrograms kg-1, intratracheally (i.t.) on lactose) inhibited antigen-induced bronchospasm in previously sensitized conscious guinea-pigs (ID50: 7 +/- 1 micrograms kg-1) and in anaesthetized rats (ID50: 100 +/- 25 micrograms kg-1). Rolipram inhibited the antigen-induced bronchospasm in guinea-pigs with an ID50 of 5 +/- 1 micrograms kg 1. In guinea-pig bronchoalveolar lavage (BAL) fluid, total inflammatory cell and eosinophil numbers were reduced by RP 73401 (ID50s: 3.9 +/- 0.8 micrograms kg-1 and 3.2 +/- 0.7 micrograms kg-1, respectively). In the rat, inflammatory cell numbers are less affected. Only the highest dose of RP 73401 (400 micrograms kg 1) significantly inhibited eosinophil influx (41 +/- 16% inhibition). 3. RP 73401 (0.02-100 micrograms kg-1, i.v.) inhibited PAF-induced bronchial hyperreactivity to bombesin in the anaesthetized guinea-pig (ID50: 0.09 +/- 0.03 micrograms kg-1) and inhibited (0.4-40 micrograms kg-1, i.t.) histamine-induced airway microvascular leakage in the anaesthetized guinea-pig by approximately 60% at all doses. 4. RP 73401 relaxed guinea-pig isolated trachea under basal tone (EC50: 9 nM) and when precontracted with histamine (IC50: 2 nM), methacholine (IC50: 29 nM) or leukotriene D4 (LTD4, IC50: 4 nM). 5. RP 73401 (0.4-100 microg kg-1, i.t.) inhibited bronchospasm induced by histamine (ID.%: 34 +/- 6 microg kg-1), methacholine (ID50: 66 +/- 12 pg kg-1) and LTD4 (ID50: <4 microg kg-1) in the anaesthetized guinea pig.Against these same bronchoconstrictors, rolipram (i.t.) had ID5o values of 44 +/- 4, 72 +/- 18 and<4 pg kg- respectively. RP 73401 (4 and 40 pg kg-, i.t.) increased the magnitude and duration of bronchodilatation produced by salbutamol in the anaesthetized guinea-pig. At doses producing significant bronchodilatation, RP 73401 was without effect on heart rate or blood pressure in the anaesthetized guinea-pig. RP 73401 (0.01 -0.25 mg kg-1, i.v.) did not affect heart rate and produced only a small fall in blood pressure in the anaesthetized rat.6. These data demonstrate that RP 73401 and rolipram inhibit antigen- and mediator-induced bronchospasmin guinea-pigs with the same potency. Furthermore, RP 73401 administered directly into the airways, protects against allergic airway inflammation. These results indicate the importance of PDE IV in regulating smooth muscle and inflammatory cell activity. At doses suppressing the inflammatory response in the lung, RP 73401 had little effect in the cardiovascular system. RP 73401 may have a role as a bronchodilator and, more importantly, as a prophylactic anti-inflammatory agent in the treatment of asthma. PMID- 7889302 TI - Stimulation by extracellular ATP and UTP of the mitogen-activated protein kinase cascade and proliferation of rat renal mesangial cells. AB - 1. Extracellular ATP and UTP have been reported to activate a nucleotide receptor that mediates phosphoinositide and phosphatidylcholine hydrolysis by phospholipases C and D, respectively. Here we report that ATP and UTP potently stimulate mesangial cell proliferation. 2. Both nucleotides stimulate phosphorylation and activation of mitogen-activated protein kinase and a biphasic phosphorylation of the up-stream mitogen-activated protein kinase kinase. 3. When added at 100 microM, ATP gamma S, UTP and ATP were the most potent activators of mitogen-activated protein kinase. beta gamma-imido-ATP was somewhat less active and ADP and 2-methylthio-ATP caused a weak induction of enzyme activity. Activation of mitogen-activated protein kinase by both ATP and UTP is dose dependently attenuated by the P2-receptor antagonist, suramin. 4. The protein kinase C activator 12-0-tetradecanoylphorbol 13-acetate, but not the biologically inactive 4 alpha-phorbol 12,13-didecanoate, increased mitogen-activated protein kinase activity in mesangial cells, suggesting that protein kinase C may mediate nucleotide-induced stimulation of mitogen-activated protein kinase. 5. Down regulation of protein kinase C -alpha and -delta isoenzymes by 4 h or 8 h treatment with phorbol ester partially inhibited ATP- and UTP-triggered mitogen activated protein kinase activation. Moreover, a 24 h treatment of mesangial cells with phorbol ester, a regimen that also causes depletion of protein kinase C-epsilon did not further reduce the level of mitogen-activated protein kinase stimulation. 6. The specific protein kinase C inhibitor, CGP 41251, which displayed a selectivity for the Ca2+-dependent isoenzymes, as compared to the Ca2+-independent isoenzymes did not inhibit nucleotide stimulated mitogen activated protein kinase phosphorylation, thus implicating the involvement of a Ca2+-independent protein kinase C isoform.7. In summary, these results suggest that ATP and UTP trigger the activation of the mitogen-activated protein kinase signalling cascade in mesangial cells and this may be responsible for the potent mitogenic activity of both nucleotides. PMID- 7889303 TI - Antimuscarinic action of liriodenine, isolated from Fissistigma glaucescens, in canine tracheal smooth muscle. AB - 1. The antimuscarinic properties of liriodenine, isolated from Fissistigma glaucescens, were compared with methoctramine (cardioselective M2 antagonist) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, smooth muscle selective M3 antagonist) by radioligand binding tests, functional tests and measurements of second messenger generation in canine cultured tracheal smooth muscle cells. 2. Liriodenine, pirenzepine, methoctramine and 4-DAMP displaced [3H]-N-methyl scopolamine ([3H]-NMS) binding in a concentration-dependent manner with Ki values of 2.2 +/- 0.4 x 10(-6), 3.3 +/- 0.7 x 10(-7), 8.9 +/- 2.3 x 10(-8) and 2.3 +/- 0.6 x 10(-9) M, respectively. The curves for competitive inhibition of [3H]-NMS with liriodenine, methoctramine and 4-DAMP were best fitted according to a two site model of binding, but pirenzepine was best fitted according to a model with one site. 3. Liriodenine and 4-DAMP displayed a high affinity for blocking tracheal contraction (pKB = 5.9 and 9.1, respectively) and inositol phosphate formation (pKB = 6.0 and 8.9, respectively), but a low affinity for antagonism of cyclic AMP inhibition (pKB = 4.7 and 7.8, respectively). 4. Methoctramine blocked cyclic AMP inhibition with a high affinity (pKB = 7.4), but it antagonized tracheal contraction and inositol phosphate formation with a low affinity (pKB = 6.1 and 6.0, respectively). 5. In conclusion, both M2 and M3 muscarinic receptor subtypes coexist in canine tracheal smooth muscle and are coupled to the inhibition of cyclic AMP formation and phosphoinositide breakdown, respectively. The antimuscarinic characteristics of liriodenine are similar to those of 4-DAMP. It may act as a selective M3 receptor antagonist in canine tracheal smooth muscle. PMID- 7889304 TI - Different endothelin receptors involved in endothelin-1- and sarafotoxin S6B induced contractions of the human isolated coronary artery. AB - 1. Endothelin receptors, that mediate contraction of the human isolated coronary artery, were characterized by use of a number of agonists and antagonists. Contraction induced by the non-selective agonists, endothelin (ET)-1 and sarafotoxin S6b, was compared in endothelium-intact and endothelium-denuded ring segments. The effects of ET-1 and BQ-123 (an ETA receptor antagonist) were investigated both in ring segments and in spirally cut strips. Lastly, the effect of phosphoramidon was studied on contraction induced by big-ET-1. 2. The order of agonist potency (pD2) in endothelium-intact coronary artery ring segments was: ET 1 (8.27) approximately sarafotoxin S6b (8.16) > big-ET-1 (< 7.1) approximately ET 3 (< 6.9). [Ala1,3,11,15]ET-1 (ETB receptor agonist) caused significant contraction only at 1 microM, whereas 0.3 microM big-ET-3 had no effect. Removal of the endothelium in ring segments did not affect the contractile response to ET 1 or to sarafotoxin S6b. 3. After a full concentration-response curve had been obtained to ET-1 or sarafotoxin S6b, further contractions of the endothelium intact coronary artery segments could only be achieved by applying ET-1 in segments exposed to sarafotoxin S6b, and not the reverse. 4. BQ-123 (0.1 microM) antagonized contractions of endothelium-intact ring segments induced by sarafotoxin S6b (pKB 7.86). Only 10 microM BQ-123 antagonized contractions induced by ET-1 (pKB 5.75). FR139317 was also more potent against sarafotoxin S6b (pKB 8.24-8.47) than against ET-1 (pKB 6.11). [Ala1,3,11,15]ET-1 (1 microM) had no effect on the contractile response to ET-1 or to sarafotoxin S6b. 5. In strip preparations with intact endothelium, the pD2 of ET-l increased to 9.04 =/- 0.16 (vs.8.50 +/- 0.07 in rings), and BQ-123 (1 microM) caused a rightward shift of the ET-l induced concentration response curve (pKB 6.62 vs. 5.75 in rings).6. Contractile responses to big-ET-1 of endothelium-intact coronary artery segments were attenuated in the presence of phosphoramidon (100 microM), indicating conversion of big-ET-1 to ET-1 within the coronary artery segment.7. The present study indicates that ET-1 and sarafotoxin S6b contract the human isolated coronary artery via different receptors, which can probably be best characterized as subtypes of the ETA receptor.Furthermore, it is demonstrated that the type of preparation (ring or strip) may affect the potency of ET-1 as an agonist and of BQ-123 as an antagonist. PMID- 7889305 TI - Possible roles of protein kinases in neutrophil chemotactic factor production by leucocytes in allergic inflammation in rats. AB - 1. In an air pouch-type allergic inflammation model in rats, leucocytes that had infiltrated into the pouch fluid collected 4 h after the antigen challenge produced proteinaceous chemotactic factors for neutrophils when they were incubated in the medium. 2. To clarify the mechanism of activation of the infiltrated leucocytes in producing these factors, the effects of protein kinase inhibitors on neutrophil chemotactic factor production were examined. 3. When the infiltrated leucocytes were incubated for 4 h in medium containing the non selective protein kinase inhibitor K-252a (1-100 ng ml-1, 2.14-214 nM), the tyrosine kinase inhibitor genistein (1-50 micrograms ml-1, 3.7-185 microM), and the more selective protein kinase C inhibitor H-7 (5-100 micrograms ml-1, 13.7 274 microM); neutrophil chemotactic activity in the conditioned medium was decreased in a concentration-dependent manner, but the adenosine 3':5'-cyclic monophosphate (cAMP)-dependent protein kinase inhibitor H-89 (1-1000 ng ml-1, 2.24-2240 nM) showed no effect. 4. Isoelectric focusing of the conditioned medium revealed that the leucocytes produced two neutrophil chemotactic factors, leucocyte-derived neutrophil chemotactic factor (LDNCF) 1 and LDNCF-2. Treatment of the leucocytes with K-252a, genistein, and H-7, but not H-89, inhibited production of both LDNCF-1 and LDNCF-2. 5. These results suggest that activation of tyrosine kinase and protein kinase C, but not cAMP-dependent protein kinase, is responsible for the production of LDNCF-1 and LDNCF-2. 6. The steroidal anti inflammatory drug dexamethasone and the protein synthesis inhibitor cycloheximide inhibited neutrophil chemotactic factor production in a concentration-dependent manner. Time-course experiments showed that the inhibitory effect by dexamethasone was apparent even 30 min after the incubation.7. Mechanism for inhibiting the production of LDNCF-1 and LDNCF-2 by dexamethasone is also discussed. PMID- 7889306 TI - Antinociceptive and toxic effects of (+)-epibatidine oxalate attributable to nicotinic agonist activity. AB - 1. Epibatidine is an analgesic substance, isolated from the skin of the poisonous frog Epipedobates tricolor, for which the mechanism of action was previously unknown. 2. The IC50 of synthetic (+)-epibatidine oxalate (the naturally occurring isomer) for [3H]-nicotine binding to rat whole-brain membranes was 0.1 nM. The (-)-isomer also exhibited high affinity (IC50 = 0.2 nM). 3. (+)- and (-) Epibatidine exhibited much lower affinity for displacement of the muscarinic ligand [3H]-N-methylscopolamine binding to rat cortical membranes (Kapp = 6.9 microM and 16.0 microM respectively). The (+)-enantiomer of epibatidine had an antagonist/agonist (NMS/oxo-M) binding ratio of 4.2 This is consistent with a muscarinic antagonist profile. 4. (+)-Epibatidine oxalate (10 microM) did not cause significant (> 30%) displacement of radioligand binding to opioid, excitatory amino acid, benzodiazepine, 5-HT, dopamine, adrenaline or peptide receptors. 5. (+)- and (-)-Epibatidine (5-20 micrograms kg-1 s.c.) doubled response latency in the mouse hot-plate test. Antinociception and behavioural depression induced by (+)-epibatidine (5 micrograms kg-1) was fully blocked by the nicotinic antagonists mecamylamine (2 mg kg-1 s.c.) or dihydro-beta erythroidine (2 mg kg-1 s.c.). The muscarinic antagonist scopolamine (0.4 and 10 mg kg-1 s.c.) caused partial reversal of antinociception induced by (+) epibatidine in mice, but not in rats. 6. These findings demonstrate that (+) epibatidine oxalate salt is a highly selective and potent nicotinic analgesic agent. PMID- 7889307 TI - Variable potency of nitrergic-nitrovasodilator relaxations of the mouse anococcygeus against different forms of induced tone. AB - 1. U46619 (thromboxane A2 receptors; 0.002-1 microM), carbachol (muscarinic M3 receptors; 0.1-100 microM), cyclopiazonic acid (CPA; Ca(2+)-ATPase inhibitor; 0.1 30 microM) and K+ (5-100 mM) produced concentration-dependent contractions of the mouse isolated anococcygeus muscle. Equi-effective, submaximal concentrations of each agent were used in further experiments (40 nM U46619; 5 microM carbachol; 5 microM CPA; 70 mM K+). 2. Nifedipine (1 microM) totally abolished contractile responses to K+; those to U46619, carbachol and CPA were reduced by only 20-30% in the presence of nifedipine, but were greatly reduced (> 90%) by a combination of nifedipine and SKF 96365 (0.1-40 microM). 3. In Ca(2+)-free medium, contractions to K+ and CPA were abolished. Small residual responses remained to both carbachol and U46619; those to carbachol were transient, could not be repeated in the continued absence of Ca2+ and were prevented by pre-incubation with CPA, but unaffected by SKF 96365; those to U46619 were sustained, could be repeated in the absence of Ca2+, and were resistant to CPA and SKF 96365. 4. Tone induced by all four agents could be relaxed by sodium nitroprusside (SNP), but with a clear order of potency. SNP (pIC40) was most effective against U46619 (7.92), less so against carbachol (6.80) and CPA (6.68), and least potent against K+ (5.94). A similar order of potency was observed with 8Br-cyclic GMP (50 microM) and nitrergic field stimulation (1-20 Hz). 5. The relaxant potency of SNP was similar in normal Krebs solution and in high K+ (70 mM) Krebs containing 1 microM nifedipine. 6. Inclusion of SNP (0.01-1 microM) or 8Br-cyclic GMP (50 microM) in the Ca2+-free medium inhibited the transient residual response to carbachol. Inclusion of similar concentrations of SNP or 8Br-cyclic GMP,during Ca2+ re-loading, increased the subsequent residual contraction to carbachol in Ca2+-free medium.7. At higher concentrations, SNP (0.1-10 microM) produced a partial relaxation of the sustained contraction to U46619 in Ca2+-free medium.8. Thus, the relaxant potency of the nitrergic stimuli was dependent on the agent and mechanism used to induce tone in the preparation. Examination of the contractile/relaxant interactions suggests that altered Ca2+ sequestration and inhibition of contractile protein function may underlie nitrergic relaxations of this tissue. PMID- 7889308 TI - A1 adenosine receptor inhibition of cyclic AMP formation and radioligand binding in the guinea-pig cerebral cortex. AB - 1. A1 adenosine receptors were investigated by radioligand binding and functional studies in slices and particulate preparations from guinea-pig cerebral cortex. 2. Binding of the adenosine receptor antagonist radioligand, 8-cyclopentyl-[3H] 1,3-dipropylxanthine (DPCPX) to guinea-pig cerebral cortical membranes exhibited high density (1410 +/- 241 fmol mg-1 protein) and high affinity (Kd 3.8 +/- 0.3 nM). 3. [3H]-DPCPX binding to guinea-pig cerebral cortical membranes was displaced in a monophasic manner by adenosine receptor antagonists with the rank order of affinity (Ki values, nM): DPCPX (6) < xanthine amine congener (XAC, 153) < PD 115,199 (308). 4. Agonist displacement of [3H]-DPCPX binding was biphasic and exhibited the following rank order at the low affinity site (Ki values): 2 chloro-N6-cyclopentyl-adenosine (CCPA, 513 nM) = N6-R-phenylisopropyladenosine (R PIA, 526 nM) = N6-cyclopentyladenosine (CPA, 532 nM) < 2-chloroadenosine (2CA, 3.2 microM) = 5'-N-ethylcarboxamidoadenosine (NECA, 4.6 microM) < N6-S phenylisopropyladenosine (S-PIA, 19.9 microM). 5. In cerebral cortical slices, [3H]-DPCPX binding was displaced by antagonists and agonists in an apparently monophasic manner with the rank order of affinity (Ki values, nM): DPCPX (14) < XAC (45) < R-PIA (266) < PD 115,199 (666) < S-PIA (21000). 6. Cyclic AMP accumulation stimulated by 30 microM forskolin in guinea-pig cerebral cortical slices was inhibited by R-PIA, CCPA and CPA up to 1 microM in a concentration dependent fashion with IC50 values of 14, 18, and 22 nM, respectively. All three analogues inhibited the forskolin response to a similar extent (82-93% inhibition). NECA, S-PTA and 2CA failed to inhibit the forskolin response, but rather enhanced the accumulation of cyclic AMP at concentrations of 100 nM or greater, presumably through activation of A2b adenosine receptors coupled to stimulation of cyclic AMP accumulation in guinea-pig cerebral cortical slices.7. The inhibition of forskolin-stimulated cyclic AMP accumulation by CPA was antagonized with the rank order of affinity (Ki values, nM): DPCPX (6) or = CGP 55845 A > CGP 52432 > or = CGP 56433 A > CGP 57034 A > CGP 57070 A > or = CGP 57976 > CGP 51176 > CGP 35348). 3. Likewise, the concentrations causing half maximal increases of [3H]-GABA in the absence or presence of (-)-baclofen, and of endogenous glutamate in the presence of (-)-baclofen, correlated well with each other. Reports in the literature suggesting the CGP 35348 exhibits a 70 fold preference for inhibition of (-)-baclofen's effects on glutamate over [3H]-GABA release, and that CGP 52432 shows a 100 fold preference in the opposite sense, could not be confirmed in our model. 4. Therefore, our results suggest that, if there are pharmacological differences between GABAB autoreceptors and GABAB heteroreceptors on glutamatergic nerve endings in the rat cortex, they are not revealed by this series of compounds of widely different potencies. 5. In particular, our results with CGP 35348 and CGP 52432 do not support the hypothesis that GABAB autoreceptors and GABAB heteroreceptors on glutamatergic nerve endings represent subtypes with different pharmacology. PMID- 7889312 TI - Display of the characteristics of endothelium-derived hyperpolarizing factor by a cytochrome P450-derived arachidonic acid metabolite in the coronary microcirculation. AB - 1. In addition to nitric oxide (NO) and prostacyclin (PGI2) an endothelium derived factor, which hyperpolarizes vascular smooth muscle cells via activation of K+ channels, contributes to the dilator effect of bradykinin in different vascular beds. Since this so-called endothelium-derived hyperpolarizing factor (EDHF) also seems to play an important role in the coronary circulation, we investigated its nature and mechanism of action in the rat isolated perfused heart (Langendorff preparation). 2. Bolus injections of bradykinin (1, 10, and 100 pmol) elicited a transient dose-dependent dilator response (e.g., 12 +/- 2% decrease in coronary perfusion pressure (CPP) at 10 pmol bradykinin, n = 41). Administration of the cyclo-oxygenase inhibitor, diclofenac (1 microM), augmented the bradykinin-induced dilation approximately twofold (n = 9 P < 0.01). Combined treatment with the NO synthase inhibitor, NG-nitro-L-arginine (30 microM) and diclofenac (1 microM) significantly reduced the duration, but increased the amplitude of the dilator response to bradykinin (27 +/- 2% decrease in CPP, n = 24, P < 0.01). 3. The abolition of this NG-nitro-L-arginine/diclofenac insensitive dilator response to bradykinin by tetrabutylammonium (0.3 mM), an inhibitor of Ca(2+)-dependent K+ channels (4 +/- 1% decrease in CPP, n = 6, P < 0.01), supports the view that the dilator compound released in the coronary microcirculation is EDHF. 4. This EDHF-type dilation was reversibly inhibited by the phospholipase A2 inhibitor, quinacrine (3 microM, 9 +/- 3% decrease in CPP, n = 6, P < 0.01) and by the cytochrome P450 inhibitor SKF525a (3 microM, 6 +/- 1% decrease in CPP, n = 6, P < 0.01). 5. Tetrabutylammonium, quinacrine or SKF 525a did not affect the endothelium-independent dilator response to sodium nitroprusside (1 nmol), indicating that these compounds did not affect smooth muscle relaxation in a non-specific manner.6. These findings suggest that in the coronary microcirculation bradykinin stimulates the release of a cytochrome P450 derived arachidonic acid metabolite, which exhibits the characteristic features of EDHF. PMID- 7889311 TI - Two populations of muscarinic binding sites in the chick heart distinguished by affinities for ligands and selective inactivation. AB - 1. By measuring the binding of N-[3H-methyl]-scopolamine ([3H]-NMS) and of unlabelled subtype-specific muscarinic antagonists, two populations of muscarinic binding sites can be distinguished in the membranes of cardiac ventricles taken from 1-day-old chicks. One of them, corresponding to approximately 80% of [3H] NMS binding sites, has higher affinities for AF-DX116 (pKi = 6.42) and methoctramine (pKi = 7.33); the rate of [3H]NMS dissociation from these sites is fast. The other population, corresponding to approximately 20% of [3H]-NMS binding sites, has lower affinities for AF-DX116 (pKi = 5.00) and methoctramine (pKi = 6.19); the rate of [3H]-NMS dissociation from these sites is slow. Both populations have high affinities for pirenzepine, but the affinity of the former (major) population is lower (pKi = 7.99) than that of the latter (minor) population (pKi = 10.14). 2. Since it has been shown earlier that two mRNAs for muscarinic receptors are expressed in the chick heart, one of them close to the genetically defined m2 and the other to the m4 subtype, we propose that the major population of binding sites with high affinities for AF-DX116 and methoctramine and the lower affinity for pirenzepine represents the M2-like receptors, while the minor population represents the M4-like receptors. 3. It proved possible to obtain isolated samples of either population by selectively protecting the M2 like sites with AF-DX116 and the M4-like sites with pirenzepine, and by inactivating the unprotected sites with benzilylcholine mustard. The properties of the isolated populations corresponded to those derived from the analysis of [3H]-NMS binding to the original mixed population.4 Alcuronium exerted positive allosteric action on the binding of [3H]-NMS both to the M2-like and the M4-like population and severely slowed down [3H]-NMS dissociation from them; its affinity for the M2-like sites was 3-10 times higher. PMID- 7889315 TI - "Teaching microbiology" vs. "learning microbiology". AB - Microbiology is great! Our challenge is to convey that excitement to our students and to stimulate them to actively pursue knowledge about microbiology. Their future will be loaded with microbial issues, ranging from safety of the hamburgers they eat to the appropriateness of the therapies for their diseases. Thus it is critical that all of our students develop problem-solving skills in microbiology. In this article, I discuss ideas about current challenges, as well as opportunities, related to teaching and learning about microbiology. PMID- 7889313 TI - Endogenous expression of histamine H1 receptors functionally coupled to phosphoinositide hydrolysis in C6 glioma cells: regulation by cyclic AMP. AB - 1. The effects of histamine receptor agonists and antagonists on phospholipid hydrolysis in rat-derived C6 glioma cells have been investigated. 2. Histamine H1 receptor-stimulation caused a concentration-dependent increase in the accumulation of total [3H]-inositol phosphates in cells prelabelled with [3H]-myo inositol. The rank order of agonist potencies was histamine (EC50 = 24 microM) > N alpha-methylhistamine (EC50 = 31 microM) > 2-thiazolylethylamine (EC50 = 91 microM). 3. The response to 0.1 mM histamine was antagonized in a concentration dependent manner by the H1-antagonists, mepyramine (apparent Kd = 1 nM) and (+) chlorpheniramine (apparent Kd = 4 nM). In addition, (-)-chlorpheniramine was more than two orders of magnitude less potent than its (+)-stereoisomer. 4. Elevation of intracellular cyclic AMP accumulation with forskolin (10 microM, EC50 = 0.3 microM), isoprenaline (1 microM, EC50 = 4 nM) or rolipram (0.5 mM), significantly reduced the histamine-mediated (0.1 mM) inositol phosphate response by 37%, 43% and 26% respectively. In contrast, 1,9-dideoxyforskolin did not increase cyclic AMP accumulation and had no effect on the phosphoinositide response to histamine. 5. These data indicate the presence of functionally coupled, endogenous histamine H1 receptors in C6 glioma cells. Furthermore, the results also indicate that H1 receptor-mediated phospholipid hydrolysis is inhibited by the elevation of cyclic AMP levels in these cells. PMID- 7889314 TI - The role of nitric oxide, adrenergic activation and kinin-degradation in blood pressure homeostasis following an acute kinin-induced hypotension. AB - 1. Nitric oxide (NO) has been suggested as the mediator of the vascular response to bradykinin. In the present study, we found that NO did not mediate the hypotensive response to bradykinin. In addition, the significance of kininase II in terminating a kinin-induced hypotension and the role of the adrenergic system in compensating for the acute fall in blood pressure (BP) was established. 2. In normal rats, the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L NAME) induced a rise in basal BP (delta BP = 40 +/- 6 mmHg, P < 0.0014) which was not altered by pretreatment with phentolamine (delta BP = 50 +/- 6 mmHg, NS). L NAME did not attenuate the acute fall in BP in response to bradykinin (3-30 micrograms kg-1) or kallikrein (6-300 micrograms kg-1). However, a significant decrease was observed in the duration of the hypotensive response (P < 0.027). This shorter duration was not observed after pretreatment with phenotolamine in addition to L-NAME. Phentolamine alone prolonged the hypotensive response to bradykinin (P < 0.04). These experiments confirm the role of NO-formation as a hypotensive component in BP homeostasis but not the role of NO as a mediator in kinin-induced hypotension. It further shows that the continuous NO-release also impedes the compensatory adrenergic hypertensive response following the acute fall in BP induced by bradykinin. 3. The hypertensive response to intravenously administered phenylephrine was found to be unchanged by preadministration of L NAME (NS) thus showing that L-NAME did not change the sensitivity to the adrenergic response. In a separate protocol on L-NAME-treated rats we found no difference in heart rate (NS) during the recovery period following bradykinin before as compared to after administration of phentolamine. It was therefore concluded that the observed alterations in the duration of the hypotensive response were most probably due to changes in peripheral vascular resistance.4. To confirm further that NO is not a mediator in kinin-induced hypotension, we used an experimental model where the response to bradykinin was prolonged by preventing kinin degradation by kininase II-converting enzyme inhibitor (CEI). To produce a hypotensive response purely dependent on kinin, the studies were performed after removal of the renin-angiotensin system by nephrectomy (Nx). In this model, bradykinin (6 microg kg-1, i.v.) induced a prolonged hypotensive response. Pretreatment with LNAME did not alter the magnitude or the progression of the hypotensive response to bradykinin, thus confirming that NO was not a mediator in BK-induced hypotension.5. To study the mechanisms involved in terminating the hypotensive response to bradykinin, the results from the Nx CEI treated rats were compared with Nx animals not treated with CEL. In the latter group,bradykinin induced a short hypotensive response, i.e. 0.5 +/- 0.1 min as compared to the 17 +/- 1 min after CEI (P<0.003). After kininase II-inhibition (and L-NAME), BP recovery was totally dependent on the adrenergic system, since phentolamine prevented a recovery in BP during the experimental period(P<0.01, compared to the CEI/L-NAME group). These results demonstrate the importance of kininase II as the major agent in terminating a bradykinin-induced hypotension, whereas the adrenergic system plays a small, although significant role in compensating for the fall in BP. The continuous release of NO therefore not only lowers basal BP but also impedes the compensatory adrenergic response. PMID- 7889316 TI - Aleutian mink disease: puzzles and paradigms. AB - Aleutian mink disease (AD) is a naturally occurring persistent virus infection of mink caused by the Aleutian mink disease parvovirus (ADV). The classical form of AD, which occurs in adult mink, is notable for high titers of antiviral antibodies, hypergammaglobulinemia, plasmacytosis, and immune complex disease. In addition, there is a progressive renal disease characterized by mesangial proliferative glomerulonephritis and severe interstitial nephritis. Development of AD depends on both host and viral factors, and mink of certain genotypes fail to develop progressive disease when inoculated with low-virulence strains of virus. In newborn mink kits, ADV causes a fatal, acute interstitial pneumonitis associated with permissive viral replication in alveolar type 2 cells, but treatment of newborn kits with anti-viral antibody aborts the acute disease and converts into one resembling the persistent infection observed in adults. In infected adult mink, ADV is sequestered as immune complexes in lymphoid organs, but actual viral replication is restricted at the level of the individual cell and can be detected in only a small population of macrophages and follicular dendritic cells. ADV infection of mink primary macrophages and the human macrophage cell line U937 is antibody dependent and leads to the production of the cytokine interleukin-6. Furthermore, levels of interleukin-6 are increased in lymph node culture supernatants from infected mink. Chronic production of interleukin-6 may promote development of the immune disorder characteristic of AD. PMID- 7889317 TI - Variant subpopulations of Staphylococcus aureus as cause of persistent and recurrent infections. AB - While S. aureus small colony variants (SCVs) have been recognized in clinical materials for decades, only recently have these strains been linked to persistent, resistant, and relapsing infections. The biochemical basis for this phenotype appears to be reduced electron transport, which leads to many changes in these organisms, including decreased alpha-toxin production. Reduced alpha toxin has been found to facilitate bacterial survival within cultured endothelial cells. This SCV subpopulation is more resistant to antibiotics, grows very slowly, and demonstrates unusual colony morphology. Hence, these resistant strains can be easily overloaded in the clinical microbiology laboratory, and may be resistant to conventional antibiotic therapy. Clinicians should ask the laboratory to search for SCVs with relapsing and resistant S. aureus infections. PMID- 7889318 TI - The optimum microbiological food safety program. PMID- 7889319 TI - Molecular pathogenesis of fungal infections. PMID- 7889320 TI - Programmed cell death: a fundamental protective response to pathogens. PMID- 7889321 TI - Restriction enzymes in cells, not eppendorfs. AB - Restriction enzymes are essential reagents to molecular biologists, but their relevance to bacterial populations is less obvious. Most bacteria encode restriction and modification systems and these are commonly considered to be a barrier to phage infection. Current evidence also supports a more general role for them in genetic recombination. PMID- 7889322 TI - Chance and selection in the evolution of barley mildew. AB - Populations of the barley powdery mildew fungus are genetically very diverse. However, when a new resistance gene is introduced into barley to control mildew, the population of the pathogen may respond by rapid growth of a few virulent clones. These phases of rapid clonal evolution cause radical changes in the frequencies of mildew genotypes. PMID- 7889323 TI - Survival of the Q fever agent Coxiella burnetii in the phagolysosome. AB - The Q fever agent, Coxiella burnetii, thrives in the acidic environment of the phagolysosome of the host cell. How this obligate intracellular agent manages to survive within this hostile milieu is unknown; however, several of its enzymes may eliminate or prevent the formation of toxic oxygen metabolites by the host cell. Also implicated as virulence factors are its surface lipopolysaccharide and plasmids. PMID- 7889325 TI - Computer processing of microscopic images of bacteria: morphometry and fluorimetry. AB - Several techniques that use computer analysis of microscopic images have been developed to study the complicated microbial flora in the human intestine, including measuring the shape and fluorescence intensity of bacteria. These techniques allow rapid assessment of changes in the intestinal flora and could apply equally to other complex microbial ecosystems. PMID- 7889324 TI - Acyclovir-resistant, pathogenic herpesviruses. AB - In herpes simplex virus, the simplest path to resistance to the drug acyclovir is a mutation that knocks out the enzyme thymidine kinase. Such mutants are highly attenuated in mouse models of viral pathogenesis, but have been reported to be associated with severe disease in immunocompromised patients. This review discusses possible resolution of this paradox. PMID- 7889326 TI - Efflux pumps and drug resistance in gram-negative bacteria. AB - The outer membrane of Gram-negative bacteria can only slow down the influx of lipophilic inhibitors, and so these bacteria need active efflux pumps of broad specificity to survive. Pumps such as the Escherichia coli Acr system and its homologs make Gram-negative bacteria resistant to dyes, detergents and antibiotics. PMID- 7889327 TI - Function of minor polypeptides in foot-and-mouth disease virus and poliovirus. AB - Foot-and-mouth disease virus and poliovirus each contain several minor polypeptides, in addition to the four structural proteins. One of these, the viral RNA polymerase, can also act as a nuclease, hydrolysing the RNA and thus destroying viral infectivity. It is tightly bound to the RNA and may be the packaging signal for assembly of the particle. PMID- 7889328 TI - Highways and strayways in classification of tumors of the central nervous system. AB - A concise review of classifications of the central nervous system tumors is presented. Special attention has been paid to subsequent histological classification of CNS tumors prepared under auspices of the World Health Organization. The author points out a necessity of the modification of WHO classification from 1979, resulting from the accumulation of new clinical and pathological observations and data on one hand and from the progress of basic research concerning neoplasia in the nervous system on the other. The author stresses the clarifying and ordering values of the classification proposals and principles, treating critically some others. Separately, the histological malignancy grading systems are reviewed. PMID- 7889329 TI - Histological classification of brain tumors, WHO, 1993--Polish translation. PMID- 7889330 TI - Molecular changes involved in the carcinogenesis of brain tumors. AB - Current basic research on tumorigenesis suggests that the accumulation of multiple genetic defects underlies the progression of initiated cells toward malignancy. Molecular abnormalities associated with primary brain tumors include a wide variety of changes in tumor-suppressor genes, proto-oncogenes and growth factors. A well-known tumor-suppressor gene, p53 gene, is located on the short arm (p) of chromosome 17 and consists of 11 exons transcribed into a 2.2-2.5 kb messenger (m) RNA that encode for a 53 kDa protein. Its alterations are associated with carcinogenesis of astrocytic tumors. Recent evidence suggests also that the p53 protein may function through promoting the expression of the recently discovered gene, WAF1/Cipl. Loss of chromosome 10 was frequently observed in glioblastoma. Southern blot analysis of glioblastomas revealed that 72% have the chromosome 10 loss and that 38% had amplification of the epidermal growth factor receptor (EGFR) gene. Autocrine stimulation of cell growth requires the presence of both growth factors and their receptors. Other genetic alterations in gliomas include elevated expression of the c-myc, Ha-ras, and c fos oncogenes with a trend to increase in higher malignant grades. PMID- 7889331 TI - Cytogenetics of astrocytomas. AB - Cytogenetic and molecular genetic analyses of all grades of human astrocytomas have provided interesting information on the mechanisms of their origin and malignant progression. Specific genetic events such as amplification and deletion are seemingly related to the stages of malignancy of astrocytic tumors. Genetic studies of human astroglial tumors can be significantly valuable as an additional tool in histopathology and in forecasting prognosis of patients. PMID- 7889332 TI - Diagnostic immunohistochemistry of tumors of the central nervous system. AB - The hopes of the early eighties for detecting a marker which would be specific for tumor cells as such or for a tumor of specific tissue or organ differentiation line have not been fulfilled. Thus, a tumor marker is a substance the level of which increases but which is not unique for tumor cells. The marker may be localized within the neoplastic cell or on its surface. The marker may also be produced by the tumor-surrounding tissue under the influence of the tumor. Therefore, the results of identifying the markers should be interpreted with great caution and should be always confronted with the routine results of light microscopy as well as other studies. This is so even if the results greatly enrich the diagnosis. The diagnostic procedures should be based also on fully standardized laboratory techniques (Taylor 1992). PMID- 7889333 TI - Analysis of morphological changes in recurrent glial tumors after surgery and telegammatherapy. AB - In 65 cases with supratentorial localized recurrent gliomas the morphological pattern of the tumors from the first and second operation was investigated. Comparison of the tumor tissue obtained for diagnosis from the first and second operation indicated blastic transformation of the tumors observed mainly in the astrocytoma group. It has been found that the transformation proceeds in a longer time since the morphological pattern of the tumors in patients with short survival either did not change or changed only to a minor degree. It was interesting to note at the second operation that tumors with signs of differentiation and clearly defined malignancy did not correlate with survival time. It seems that the primary histological pattern of the tumor determines the survival time after the first operation. PMID- 7889334 TI - Expression of p53-protein, epidermal growth factor receptor (EGFR) and proliferating cell antigens in human gliomas. AB - Paraffin-embedded surgical specimens from 56 human astrocytomas (8 pilocytic [I degree] astrocytomas, 9 low grade [II degrees] fibrillary astrocytomas, 9 high grade [III degrees] astrocytomas and 30 glioblastomas) were immunostained with the anti-PCNA, anti-p53, anti-Ki-67 and anti EGFR antibodies. Approximately 41% of all cases were p53 protein-positive while 23% were EGFR positive. Five cases (8.9%) were positive for both p53 protein and EGFR. Low grade gliomas showed low PCNA LI while high PCNA LI was observed in high grade gliomas. The same trend was observed with anti-Ki-67 antibodies but the proportion of Ki-67 immunolabelled cells was always much lower. In conclusion, we found two populations of astrocytic tumors with EGFR and with p53 protein overexpression but no dependence between p53 immunoreactivity and PCNA or Ki-67 LI. PMID- 7889335 TI - Expression of N-myc, c-myc and c-erbB-1 proto-oncogenes in cerebral primitive neuroectodermal tumors (PNET). AB - Neuroectodermal tumors demonstrate a relatively high incidence of proto-oncogenes amplification. This study attempted to determine the frequency of overexpression of three genes: N-myc, c-myc and c-erbB-1, in human PNET. Immunohistochemical studies revealed 5 to 74% neoplastic cells with positive immunoreactivity to anti c-myc antibody in all investigated samples. In 3 cases the reactivity was particularly strong and present in more than 50% of tumor cells. Northern blot analysis revealed normal (2.3-kb in size) but significantly higher level of c-myc transcripts in these cases. By using anti-EGFR antibody 3 tumors disclosed 10 to 65% neoplastic cells with positive immunoreactivity. There was no rearrangement detected of their c-erbB-1 or N-myc genes by means of applied methods. Our results suggest that overexpression of c-myc gene is present in 10% of PNET but it is not the consequence of gene amplification. Amplification of N-myc and c erbB-1 are rare events during PNET development. PMID- 7889336 TI - Immunohistochemical study in two cases of dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos disease). AB - We report here immunohistochemical study of two cases of dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos disease) a rare entity which is recently classified as a tumor but which hamartomatous nature is also considered. Dysplastic cells of our cases expressed neuronal markers (synaptophysin and NFP), thus their origin from neurons or neuronal precursor is clearly demonstrated. The exact progenitor cell is, however, unknown. The glial involvement was not easily judged based on our histochemical study. While a few GFAP-immunopositive astrocytes were seen in all specimens, including the recurrence of the first case, they appeared of normal size and non hypertrophic in the second case. Furthermore, they did not much increased in number in the recurrent tumor. Thus, it seems that they are not the primary target for the pathogenetic process, whatever it is, of Lhermitte-Duclos disease. PMID- 7889337 TI - Pleomorphic xanthoastrocytoma and desmoplastic infantile ganglioglioma--have these neoplasms a common origin? AB - We report a case of a 24-year-old woman with left temporal pleomorphic xanthoastrocytoma (PXA) with atypical neuronal cells. Many neoplastic cells, otherwise typical of PXA, expressed glial fibrillary acidic protein, while neuronal cells with marked atypia were immunopositive for synaptophysin and neurofilament protein. This report supports a notion that PXA, like other astrocytic tumors, may has its gangliogliomatous counterpart as superficial cerebral astrocytoma of infancy has it in desmoplastic infantile ganglioglioma. PMID- 7889338 TI - Multifocal central nervous system glioma--a case history. AB - A case history of the multifocal brain glioma in 13-year-old girl is reported. Numerous neoplasmatic foci were found using MRI within the vermis and cerebellar hemisphere and, later, also within the brain stem, cervical spinal cord and both brain hemispheres. Bioptical examination of the tumors revealed the structure of anaplastic astrocytoma with oligodendromatous component. The authors suggest that the foci may be considered as multiple metastases from the primary cerebellar astrocytoma and the neoplastic cells might have been transported within CNS through cerebrospinal fluid. PMID- 7889339 TI - Gliomatosis cerebri at the 17-year-old girl--correlations of histological, CT and MRI appearance. AB - The neuropathologic findings are compared with CT scans and MRI in the case of gliomatosis cerebri; a 17-year-old girl died 2 years after the first epileptic seizure and the onset of neurologic signs. CT scans showed two poorly defined, hypodense foci: the major one in the left parietal white matter and the minor one in the right frontal white matter. MRI demonstrated on T2 weighted image bilateral diffuse increased signal intensity changes with focal high signal mass in the right frontal white matter and cortex as well as in the left occipito temporal white matter and cortex. The brain coronal sections showed widespread and diffuse neoplastic infiltration in both cerebral hemispheres: corpus callosum, basal ganglia, brainstem and cerebellum. In the microscopic examination diffuse gliomatous infiltration was found. PMID- 7889340 TI - Reaction of microglial cells in human astrocytomas (preliminary report). AB - Forty human primary brain tumors: twelve protoplasmic, six gemistocytic, four fibrillary and ten anaplastic astrocytomas, eight glioblastomas were submitted for immunohistochemical and histochemical characterization of microglia in tumor tissue and in its surroundings. The following antibodies were used: GFAP, ferritin, CD45RO and lectin RCA-1. It was found that the greatest number of ramified microglia occurred in gemistocytic astrocytomas. In the protoplasmic and fibrillary astrocytomas both the ramified and amoeboid microglia were observed. In glioblastomas and anaplastic astrocytomas the greatest number of amoeboid microglia and very rarely ramified microglial cells were found. It is suggested that differences between the various kinds of astrocytomas determine the difference in the type of microglia reaction. It is assumed that this might be caused by the differences in secreting some factors by these tumors astrocytes. PMID- 7889341 TI - Intracranial meningiomas following irradiation therapy for brain tumors. AB - Two cases of radiation-induced meningiomas following therapeutic irradiation given for primary diagnosed malignant brain tumor are presented. The meningiomas, histologically different from the initial brain tumor, appeared 15 and 21 years after high-dose brain irradiation. The possible risk of carcinogenesis within the CNS resulted from therapeutic cranial irradiation is stressed. PMID- 7889342 TI - Multiple disseminated meningioma. Case report. AB - A case of 32-year-old woman was described in which progressive bilateral hearing and visual loss, hypokinesia, epileptic focal seizures were present. The brain CT scan after a few years of the disease onset, showed the presence of multiple extracerebral tumors. Multiple meningiomas were diagnosed, probably associated with von Recklinghausen's disease. On the post-mortem examination 48 tumors of the different size and location in subdural space were found. Histologically transitional meningiomas with predominance of fibroblastic component were diagnosed. It was very interesting that apart from intracranial location of meningiomas, the same type of tumor was found within thoracic spinal root. The authors discuss the mechanisms of the development of multiple meningiomas and its association with neurofibromatosis. PMID- 7889343 TI - Microcystic meningioma--a rarely occurring morphological variant of meningioma. AB - Two cases of microcystic meningioma are reported. They were found by retrospective study of 124 human intracranial meningiomas. Both of the examined tumors were characterized histologically by a great number of cysts of various size intermixed with nests of neoplastic tissue of meningothelial meningioma type. Nevertheless, there were two kinds of cystic changes in these tumors. In the first case, numerous microcysts within the tumor were surrounded by stellate shaped processes of meningioma's cells. The microcystic space were empty or rarely contained eosinophilic material. The latter tumor demonstrated small agglomerations of microcysts and many macrocystic changes, some of them filled with eosinophilic, PAS and mucicarmine negative material. Additionally, in focal areas of the tumor, single mitotic figures and giant cells with hyperchromasia were present. The authors discuss morphologic variability of the examined tumors and its possible clinical consequences. The pathogenesis of microcystic changes in meningioma is discussed with a brief review of the literature. PMID- 7889344 TI - Metastatic carcinoid tumor in the brain. AB - The case presented describes a metastatic carcinoid in the cerebral hemisphere of a 52-year-old woman. The onset of the disease was in the form of stroke, CT examination showed hemorrhagic focus and edema. A craniotomy was carried out and the lesion was removed. Histological diagnosis stated that the tumor was a carcinoid accompanied by a massive hemorrhage. Two and a half months later, another CT-examination revealed a second tumor in proximity to the site of operation, which was then treated palliatively by means of Co 60 radiation. The patient died 1.5 months later. General autopsy showed two other neoplastic tumors: a smaller one in the left lung and a bigger one (possible primary) in the stomach. In the report special attention was paid to an unusual cellular polymorphism especially prominent in the tumor formerly irradiated. PMID- 7889345 TI - Effects of PCBs (Aroclor 1254) on reproduction and growth rate in Mongolian gerbils (Meriones unguiculatus). AB - Groups of female Mongolian gerbils were subcutaneously administered 2mg or 4mg PCBs (Aroclor 1254) in 0.1ml oil or vehicle only after pairing for two days with untreated males. No effects were found on the number of pairs breeding, birth intervals, number of pups per litter or percentage of male offspring. The preweaning growth rates of the PCBs exposed first litter offspring was retarded, but second litters showed no differences compared to controls. No other differences in growth were observed. PMID- 7889346 TI - Uptake of organochlorines (chlorobiphenyls, dieldrin; total PCB & DDT) in bottlenose dolphins (Tursiops truncatus) from Cardigan Bay, west Wales. AB - High concentrations of organochlorine compounds (particularly PCB and chlorobiphenyls) have been found in three bottlenose dolphins from the vicinity of New Quay in West Wales. Although few in number, the animals ranged in age from 10 months to 23 years. The occurrence of high contaminant concentrations in all of these animals suggests that a high level of uptake of these compounds occurs in food after weaning as well as by transfer from mother to calf. In order to investigate this further we have tried to model the uptake using a bioenergetics based approach. Using estimates of feeding rate we have calculated the concentrations of these contaminants in average prey items necessary to maintain the dolphin's body burden during the juvenile growth stage. The data available to date are too few for a rigorous test of this approach, however these preliminary studies suggest that the contaminant concentrations in local food items analysed to date are not sufficiently high to explain the high concentrations found in dolphin blubber. Further information is needed on the contaminant burdens of bottlenose dolphins in Cardigan Bay, and of their relationships and diet (including seasonal and migratory components), in order to validate this approach. PMID- 7889347 TI - Biodegradation of alkyltrimethylammonium salts in activated sludge. AB - Trimethylamine, dimethylamine and methylamine (actually existing as a salt form in the culture medium) were identified as the intermediates of alkyltrimethylammonium salts in activated sludge obtained from a municipal sewage treatment plant. It was considered that the quaternary ammonium salts with long alkyl chains were degraded to tertiary amine by N-dealkylation at the first stage of the biodegradation pathway. The tertiary amine formed in this pathway rapidly disappeared. In the activated sludge, biodegradabilities based on biochemical oxygen consumption and dissolved organic matter were 7.2-53.7% and 97.4-100%, respectively. These results and the disappearance of intermediates as described above indicate that long chain alkyltrimethylammonium salts are ultimately biodegradable. PMID- 7889348 TI - Polyfluorinated dibenzodioxins and dibenzofurans--synthesis, analysis, formation and toxicology. AB - The 75 congeners of the polyfluorinated dibenzodioxins (PFDDs) and about half of the 135 polyfluorinated dibenzofurans (PFDFs) have been synthesized by pyrolysis of fluorophenols and fluorobenzenes. The individual congeners were characterized by GC/MS. 2,3,7,8-TFDD was also characterized by 1H-, 13C- and 19F-NMR spectroscopy. The retention behaviour of PFDDs and PFDFs during gaschromatographic separation is entirely different from that of PCDDs/PCDFs or PBDDs/PBDFs. The PFDDs/PFDFs elute earlier than the PCDDs/PCDFs and the order of the elution is not governed by the degree of substitution, O8FDD eluting e.g. much earlier than the M1FDDs. A preliminary toxicological evaluation of 2,3,7,8 TFDD was carried out. The elimination of 2,3,7,8-TFDD from mice after a single i.p. injection is biphasic with a very rapid elimination half-life of 5 minutes and a slower phase of 165 minutes. This means a dramatically reduced half-life compared to 2,3,7,8-TCDD with 8.5 d. In liver the TFDD level reaches a maximum 30 minutes after injection and also declined in a biphasic manner. In rat hepatocytes a primary culture induction of CYP4501A1-catalyzed EROD activity could be demonstrated, indicating that 2,3,7,8-TFDD activates the dioxin receptor. In rat hepatocyte cultures similar EC50 values were found for 2,3,7,8 TCDD and 2,3,7,8-TFDD. So far no de novo synthesis of PFDD/PFDF could be detected under conditions were PCDDs/PCDFs are formed. Also, formation of PFDDs/PFDFs could not be detected during thermal treatment of fluorotrichloromethane or Teflon. PMID- 7889349 TI - Bioassay-directed chemical analysis of genotoxic components in urban airborne particulate matter from Barcelona (Spain). AB - Organic extracts of airborne particulate matter, collected in the city of Barcelona, were subjected to three-level, bioassay-directed, chemical fractionation, including gel permeation chromatography (GPC) and normal-phase (NP) and reversed-phase (RP) liquid chromatography (LC). The chemical characterization, directed by the Salmonella microsome mutagenicity assay (TA98, TA98NR and TA98/1,8DNP6 +/- S9), was carried out by capillary GC (CGC) coupled to selective detection systems, and by GC-MS techniques. The results obtained with the nitroreductase deficient strains show the important contribution of nitroaromatic compounds. Detailed chemical analysis of the mutagenic fractions led to the identification of 82 aromatic compounds and revealed the large contribution of chemical classes that are more polar than polycyclic aromatic hydrocarbons such as aromatic ketones, quinones and aldehydes. PMID- 7889350 TI - 32P-postlabeling analysis of aromatic DNA-adducts in liver and brain of wild brook trout (Salvelinus fontinalis). AB - Several studies have reported the absence of DNA-adducts in fish collected from unpolluted areas. We determined DNA-adduct levels in liver and brain tissue of wild brook trout (Salvelinus fontinalis) from remote areas of Newfoundland and sub-arctic Labrador, that have no known input of anthropogenic contamination. Varying levels of adducts were detected in both liver and brain, at all locations. Hepatic adduct levels were generally higher than those in brain tissue. Tissue-specific differences in adduct levels and the possible effects of long range transport of air pollutants (LRTAP) are discussed. PMID- 7889351 TI - Form of mercury in stream fish exposed to high concentrations of dissolved inorganic mercury. AB - The form of mercury predominating in mercury-contaminated fish from both pristine and industrialized waters in North America and Europe has almost universally been methylmercury. Sunfish (Lepomis auritus) living in a stream contaminated with 0.5 1 micrograms/L dissolved inorganic mercury accumulated greater concentrations of total mercury at headwater sites, where the dissolved mercury concentrations were greatest, than they did at downstream sites. However, despite evidence from laboratory studies that dissolved inorganic mercury is rapidly accumulated by fish without transformation to methylmercury, methylmercury constituted 85% or more of the total mercury concentration in fish at all sites. PMID- 7889352 TI - The elimination and estimated half-lives of specific polychlorinated biphenyl congeners from the blood of female monkeys after discontinuation of daily dosing with Aroclor 1254. AB - The levels of thirty polychlorinated biphenyl congeners in the blood of female rhesus monkeys, previously dosed with Aroclor 1254 for over six years, were monitored every two weeks during the first year and monthly during the subsequent two years after dosing was discontinued. Both blood lipid and polychlorinated biphenyl congener levels generally declined during this post dosing period. The percent distribution of the PCB congeners during the post dosing period remained relatively constant with more than half of all polychlorinated biphenyls consisting of the mono-orthochlorine substituted biphenyls. The contribution of the mono-orthochlorine substituted biphenyls was significantly different for one out of three monkeys in two of the three dose groups, during the post dosing period. Half-life, estimations for nine of the congeners ranged from 0.3-7.6 years. PMID- 7889353 TI - Selenium content of Brazil nuts from two geographic locations in Brazil. AB - Brazil nuts (Bertholletia excelsa) natively contain very high concentrations of selenium. Since dietary selenium, including Brazil nuts, have been associated with protection against tumor development in laboratory animal studies, it was of interest to determine the selenium content of the nuts from different nut-growing regions of Brazil. In the work reported, 162 nuts from each of two regions (Acre Rondonia and Manaus-Belem) were individually analyzed for selenium. The average +/- standard deviation and range of selenium concentrations in ppm, fresh weight for nuts from Acre-Rondonia and Manaus-Belem regions were, respectively, 3.06 +/- 4.01 (0.03-31.7) and 36.0 +/- 50.0 (1.25-512.0). The toxicology of Brazil nut consumption is discussed. PMID- 7889354 TI - Residues of arsenic and lead in potato soils on Long Island. AB - Sodium arsenite was used for vine control and fall weed control in potatoes on Long Island for many years. Lead arsenate may also have been used as an insecticide in certain areas. A study was conducted to determine remaining concentrations of arsenic and lead in potato soils on Long Island. The total concentrations of both arsenic and lead were markedly higher in the soils sampled than in untreated control soils. The behavior of arsenic and lead in soils is discussed. PMID- 7889355 TI - Analytical survey of elements in veterinary college incinerator ashes. AB - While appreciable attention has been given to the elemental composition of ashes from municipal solid waste incinerators, relatively little information is available on the elemental content of incinerators burning animal carcasses and medical wastes. In the work reported here, an analytical survey was conducted of the concentration of 22 elements in the ashes of incinerators located at veterinary colleges or animal disease diagnostic laboratories in seven states. With the exception of Zn, the concentrations of most elements were well below those found in ashes from municipal solid waste incinerators. Conversely, Ca, P and K were much higher in concentration probably deriving largely from bones, teeth and other organs of animals. There was an indication that burned plastic wastes were a source of Pb in the ashes. The concentrations of several toxic elements varied widely probably due to variations in initial waste composition, incinerator design and operating parameters. The concentrations of soluble salts in the ashes were appreciable. Organic matter in the ashes was low to nondetectable indicating the completeness of incineration. PMID- 7889356 TI - Critical factors of intracerebral microdialysis as a technique to determine the pharmacokinetics of drugs in rat brain. AB - The purpose of this investigation was to determine the effect of experimental conditions on the concentrations of atenolol and acetaminophen in brain microdialysate, and to investigate the feasibility of performing repeated experiments within individual rats. Following intravenous bolus administration, reproducible concentration-time profiles were obtained in plasma and in brain dialysate. Based on corrections for in vitro recoveries of the intracerebral probe, the estimated ratio of the AUC in brain extracellular fluid (AUCbrain ECF) over the AUC in plasma (AUCplasma) +/- S.E.M. was 3.8 +/- 0.6% (n = 6) for atenolol and 18 +/- 2% (n = 6) for acetaminophen. Upon intracerebroventricular administration, interanimal differences in kinetics of acetaminophen in brain dialysate were observed while the concentrations of atenolol were below the detection limit of the assay. The influence of the use of isotonic versus hypotonic perfusate solutions on AUCbrain ECF values after intravenous bolus administration of both drugs was determined. Repeated experiments with the isotonic perfusate (24, 48 and 78 h post-surgery) resulted in AUCbrain ECF values with the ratio of 100: 98: 76% for acetaminophen and 100: 103: 98% for atenolol. Using a hypotonic perfusion solution the ratio of AUCbrain ECF values was 100: 154: 114% for acetaminophen and 100: 378: 427% for atenolol. A clear effect of the temperature of the hypotonic perfusate (24 vs 38 degrees C) on acetaminophen AUCbrain ECF values was revealed. The ratio of AUCbrain ECF values obtained at 24: 38 degrees C was 192: 100%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889357 TI - Descending modulation of central neural plasticity in the formalin pain test. AB - Subcutaneous injection of formalin produces a biphasic profile of pain response: a transient early phase followed by a tonic late phase. A number of studies have indicated that the development of the late phase of formalin pain is dependent upon prolonged changes in central neural function produced by neural activity that is generated during the early phase (i.e. central sensitization). In support of this, the present demonstrates that stimulation- or morphine-produced analgesia derived from the periaqueductal grey (PAG) during the early phase prevents the development of the phase. These results suggest that descending mechanisms of pain inhibition, as reflected by PAG stimulation- and morphine produced analgesia, can prevent the development of central neural plasticity following injury. PMID- 7889358 TI - Chloride conductance produces both presynaptic inhibition and antidromic spikes in primary afferents. AB - Primary afferents from a crayfish leg proprioceptor display both primary afferent depolarizations (PADs) and antidromic spikes. PADs are generated by activation of GABA receptors and produce presynaptic inhibition, while the antidromic spikes do not elicit any synaptic effect in the postsynaptic neurons. The aim of the present study was to investigate the ionic mechanisms that allow PADs to produce antidromic spikes and to test whether GABA can produce similar effects. Intracellular recordings from the sensory axon terminals within the ganglion where PAD are produced were performed. Lowering the extracellular chloride concentration resulted in an increase in PAD amplitude, which was then capable of producing antidromic spikes. Local application of GABA close to the axon terminal also resulted in production of antidromic spikes. We conclude that antidromic spikes may result from the activation of a GABA-mediated increase in chloride conductance that also produces PADs. Therefore PADs and antidromic spikes may represent two aspects of the same GABAergic inhibitory mechanism that gate sensory transmission. PMID- 7889359 TI - Effects of intrathecal naloxone and atropine on the nociceptive suppression induced by norepinephrine and serotonin at the spinal level in rats. AB - The interrelations among norepinephrine (NE), serotonin (5-HT), opiate-like substances (OLS), and acetylcholine (ACh) were investigated by using electrophysiological method combining with intrathecal (i.t.) injection. The results show that: (1) pretreatment with i.t. naloxone (Nal) completely reversed the NE-induced suppression of nociceptive discharges in parafascicular (PF) neurons, but partially reversed that of induced by i.t. 5-HT; (2) pretreatment with i.t. atropine (Atr) completely reversed the suppression induced by either NE or 5-HT. The results suggest that OLS may act as a necessary mediator for NE induced suppression on the spinal transmission of nociceptive inputs, while it is only partially involved in the 5-HT-induced suppression, and moreover, that endogenous ACh is necessary for the performance of nociceptive suppression induced by either spinal NE or 5-HT administration. PMID- 7889360 TI - Unilateral deficits induced in rats by MPP+ are markedly reduced by an N-terminal peptide fragment of dopamine-releasing protein. AB - Dopamine-releasing protein (DARP) is a novel factor involved in the function and development of catecholaminergic systems. To test whether a peptide synthesized from the N-terminus of DARP (DARP-36aa) ameliorates deficits in nigrostriatal dopamine, rats were unilaterally lesioned with MPP+, 1 day before administration of DARP-36aa began. Striatal delivery of 1 microgram DARPP-36aa daily for 10 days elevated striatal dopamine (P < 0.01) and reduced amphetamine-induced rotations (P < 0.05) relative to controls, both indicating the protection or restoration of dopaminergic function. PMID- 7889361 TI - Increased expression of heme oxygenase mRNA in rat brain following transient forebrain ischemia. AB - Heme oxygenase is a rate-limiting enzyme in heme catabolism, the end of which include iron, carbon monoxide and bilirubin. Expression of the inducible form of heme oxygenase (HO-1) was investigated in rat brain following 20 min of forebrain ischemia by Northern blot and in situ hybridization analyses. The level of HO-1 mRNA was undetectable in the cerebral cortex of sham control, but increased following ischemic insult, reached the maximum after 12 h of reperfusion, and then decreased. In sham control brain, HO-1 mRNA was detectable only in the scattered neuron-like cells within the dentate gyrus hilus. At 12 h of reperfusion, the remarkable increase in HO-1 mRNA levels was observed in both neuronal and glia-like cells distributed in the neocortex, hippocampus and thalamus. PMID- 7889362 TI - Discharge frequencies and intervals between pulses: are they always the same? AB - Neuronal discharge recorded as action potentials with intervening interpulse intervals can be converted to a frequency format. The ease of this interconversion masks two important problems in this process. For the same data set, the dynamics of change with the measured variable will be different for each of these two methods of characterizing discharge and each of these forms of rate indexing will have a different mean value. In all neuronal discharge studies, it may be initially necessary to determine whether normal population statistics apply to the primary data expressed in the IPI-mode or in the Hz-mode. PMID- 7889363 TI - Effects of electro-acupuncture and physical exercise on regional concentrations of neuropeptides in rat brain. AB - The effects of single or repeated treatments with manual acupuncture (ACU), electro-acupuncture (ELACU) or physical exercise on neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP), galanin (GAL) and vasoactive intestinal peptide (VIP)-like immunoreactivity (-LI) in different regions of the rat brain were studied. Initially the effect of microwave irradiation (MWI) was compared to decapitation on the recovery of neuropeptides, and significantly higher concentrations of SP-LI, NKA-LI and NPY-LI were found in the hippocampus, occipital cortex, pituitary and striatum following MWI. Repeated ELACU treatments significantly increased SP-LI, NKA-LI and NPY-LI in the hippocampus and NPY-LI in the occipital cortex. No changes were found in animals receiving ACU or performing physical exercise. PMID- 7889364 TI - Spreading depression of Leao in rodent and human cortex. AB - Spreading depression (SD) has been implicated in the pathophysiology of a number of neurological conditions. The same methodology was used to elicit SD in anesthetized rats and in non-anesthetized patients undergoing cortical resections for intractable epilepsy. A slowly spreading DC potential shift (mean -9 mV) occurred in the cortex of 10 of 15 rats in association with attenuation of the electrocorticogram but this could not be reproduced in any of the human cortices (n = 23) where the mean potential shift was -0.56 mV (P < 0.0001). SD is more difficult to elicit in human than rodent cortex and may not occur in man. PMID- 7889365 TI - Developmental changes of neurotrophin-3 level in the mouse brain detected by a highly sensitive enzyme immunoassay. AB - Levels of neurotrophin-3 (NT-3) in the mouse brain were measured by a highly sensitive enzyme immunoassay (EIA). The monoclonal antibody, 3W3, was labeled with beta-galactosidase, followed by measurement of galactosidase activity. The detection limit of the EIA system was 0.4 pg/well (4 pg/ml). At 1 and 8 weeks of age, the highest level of NT-3 was detected in the hippocampus, a relatively high level also observed in the cerebellum. In contrast, in the cortex, the striatum, the diencephalon, the midbrain, and the brainstem, NT-3 levels were low. Furthermore, we examined the developmental changes of NT-3 level in the hippocampus and the cerebellum. In the hippocampus, the NT-3 levels were more than 20 ng/g tissue from 1 week to 14 weeks of age, but at 20 weeks of age the level decreased to about half. In the cerebellum, although the NT-3 level was high at 1 week of age, the levels were gradually decreased to one-fourth by 20 weeks of age. In peripheral tissues, a large amount of NT-3 protein was observed in the heart. PMID- 7889366 TI - Expression and characterization of the alpha 2 subunit of the alpha-amino-3 hydroxy-5-methyl-4-isoxazole propionate (AMPA)-selective glutamate receptor channel in a baculovirus system. AB - Using a baculovirus expression vector system, the alpha 2 subunit of the mouse alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-selective glutamate receptor (GluR) channel was expressed in Spodoptera frugiperda insect cells. Immunoblotting using the antibody made to the synthetic peptide corresponding to the C-terminus of GluR alpha 2 and [35S]methionine/[35S]cysteine metabolic radiolabeling revealed the major 102-kDa and the minor 98-kDa protein bands. Metabolic radiolabeling with tunicamycin suggested that the two bands correspond to glycosylated and unglycosylated forms, respectively. The recombinant GluR alpha 2 proteins expressed in insect cells were also identified by immunofluorescence staining. The results of [3H]AMPA binding assay using whole cells suggested that, in infected Sf21 cells, binding sites of the GluR alpha 2 proteins were possibly located on the extracellular side. Scatchard analysis of AMPA binding showed the following parameters: Kd = 16 nM, Bmax = 1.9 x 10(5) binding sites per cell or 1 pmol/mg protein in the total particulate fraction. The ligand binding characteristics of the receptors expressed in insect cells were examined. From the effect of various agonists on [3H]AMPA binding of the receptors expressed in insect cells, the rank order potency of agonists was quisqualate > AMPA > L-glutamate > kainate. Thus, the baculovirus-insect cell expression system provides high-efficiency expression of the receptor sufficient to permit structural and functional analyses. PMID- 7889367 TI - Elevated neuronal c-Fos-like immunoreactivity and messenger ribonucleic acid (mRNA) in genetically obese (ob/ob) mice. AB - Adult genetically obese (ob/ob) mice display a number of metabolic alterations, the primary cause of which may be a defect in their central nervous system (CNS). The protein encoded by the protooncogene c-fos, c-Fos, functions as a nuclear transcription factor, and also serves as a marker of neuronal activity. The specific objectives of this study were (1) to use c-Fos immunohistochemistry to identify regions with altered neuronal activity in 6-7 week old male lean and ob/ob mice; (2) to examine c-fos relative mRNA abundance by northern blot analysis in brains of these mice and compare it with that of neuropeptide Y (NPY), a peptide well known to alter feeding and (3) determine changes in c-Fos immunoreactivity and mRNA caused by food deprivation. Fos-like immunoreactivity (FLI) tended to be higher in ad libitum fed ob/ob mice than in lean controls in most brain regions examined. The most prominent and consistent differences were in the paraventricular nuclei (PVN) where the numbers of Fos-positive nuclei were approximately 3 fold higher in ob/ob mice. Food deprivation for 24 h increased FLI in the PVN in lean mice but did not further augment FLI in the PVN of ob/ob mice. Arcuate nuclei of lean and ob/ob mice showed minimal FLI staining under ad libitum fed conditions. Food deprivation however, induced FLI in arcuate nuclei of both lean and ob/ob mice. The abundance of c-fos mRNA in whole brain of ob/ob mice averaged several fold higher than in leans under both fed and fasted conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889368 TI - Basal forebrain injections of the benzodiazepine partial inverse agonist FG 7142 enhance memory of rats in the double Y-maze. AB - Cholinergic replacement strategies have achieved little success in the treatment of Alzheimer's disease. It has been suggested that the mnemonic function of cholinergic neurons may be enhanced by treatments that reduce GABA-ergic inhibition, while preserving the normal pattern of activity in the cholinergic neurons. Following on these suggestions, the present study investigated the mnemonic effects of intra-nucleus basalis magnocellularis (NBM) injections of the benzodiazepine receptor partial inverse agonist N-methyl-beta-carboline-3 carboxamide (FG 7142). Rats were surgically implanted with bilateral cannulae in the NBM prior to training in a double Y-maze. Daily training sessions continued until reference and working memory choice performance stabilized to a criterion of > or = 91% correct. Rats (n = 9) received FG 7142 bilaterally in doses of 0.2, 2.0 and 3.0 micrograms/0.5 microliter per side, muscimol (a GABAA agonist) in a dose of 0.1 microgram/0.5 microliter per side, vehicle (345 micrograms 2 hydroxypropyl-beta-cyclodextrin/0.5 microliter saline per side) or no injection in a counterbalanced order with retraining to criterion between treatments. Muscimol impaired choice accuracy on both the reference and working memory components, but the effect was bigger for working memory, replicating our previous findings. Two doses of FG 7142 (0.2 and 2.0 micrograms/0.5 microliter) enhanced choice accuracy on the working memory component. The present results suggest that benzodiazepine partial inverse agonists may enhance mnemonic function. PMID- 7889369 TI - High sensitivity of the turtle olfactory system to nonvolatile substances: comparison of response properties with those in gustatory systems. AB - The olfactory responses of the aquatic turtles, Geocylemys reevesii whose nostrils are closed underwater to nonvolatile substances were measured by recording the olfactory bulbar responses. Various salts, acids and bitter substances elicited large responses, while sugars and amino acids did not elicit the responses. The thresholds for the salts were much lower than those of corresponding salts in the rat gustatory system. The responses to the salts were partially suppressed by amiloride. Various acids induced large responses and the magnitudes greatly depended on the anion species. The thresholds for the bitter substances were much lower than those of corresponding substances in the taste systems. Similar to the responses in taste systems, both electrostatic and hydrophobic interactions contribute to the binding of the substances to the receptor membranes. Similar to the taste systems, the response to quinine hydrochloride showed a sharp temperature dependence having a peak around 25 degrees C, while the responses to odorants did not show such peak. The present results suggest that the olfactory system has similar abilities to respond to salts, acids and bitter substances to those in gustatory systems and that the high sensitivity of the olfactory system to chemical stimuli is not only attributable to the second messenger amplification system, but also to the basic property of the receptor membrane independent of the amplification system. PMID- 7889370 TI - Alterations in central catecholamines associated with immune responding in adult and aged mice. AB - Central catecholamine alterations associated with immune activity are similar to those seen following stressor exposure. Inasmuch as aged animals exhibit more pronounced stressor-provoked alterations of central amines relative to younger animals, it was of interest to determine whether immune challenge would similarly induce more pronounced central amine variations in older animals. Fifteen-month old CD-1 mice challenged with 10(7) sheep red blood cells (SRBC) revealed an equivalent peak splenic plaque-forming cell response (4 days after antigen challenge) to that of 3-month-old mice challenged with 10(6) cells. Neither plasma adrenocorticotropic hormone (ACTH) nor corticosterone levels varied over days following immunization, although ACTH levels were generally higher in the older mice. In both age groups reductions of hypothalamic and locus coeruleus norepinephrine (NE) and increased accumulation of the metabolite MHPG coincided with (or preceded by 24 h) the peak immune response. However, increased accumulation of MHPG in the hypothalamus was greater and occurred earlier in the locus coeruleus of the aged mice. Likewise, at or about the time of peak immune responses nucleus accumbens dopamine (DA) levels were reduced and metabolites elevated in both age groups, while in the prefrontal cortex only DA metabolite levels were elevated. These data are commensurate with previous findings showing that SRBC inoculation may influence central neurotransmitters and that such effects correspond with the time of the peak immune responses. Moreover, in so far as hypothalamic NE utilization is concerned, it seems that the effects of SRBC inoculation are more pronounced in aged animals. PMID- 7889371 TI - High- and low-affinity NMDA receptor-binding sites in rat spinal cord: effects of traumatic injury. AB - N-methyl-D-aspartate (NMDA) receptor-mediated events have been implicated in the pathophysiology of posttraumatic spinal cord injury. In the present study, [3H]MK801 was used to analyse the changes in NMDA receptor-binding sites in rat spinal cord after impact trauma at T9. In contrast to brain, which showed only a single binding site, spinal cord showed both high-affinity (Kd1 = 0.47 +/- 0.24 nM) and low-affinity (Kd2 = 7.75 +/- 1.82 nM) binding sites with relatively low binding density (Bmax1 = 0.11 +/- 0.04 pmol/mg protein and Bmax2 = 0.84 +/- 0.11 pmol/mg protein). Time-course studies demonstrated significant decreases in the binding of [3H]MK801 at the thoracic and lumbar segments at 4 h after spinal cord injury with recovery by 24 h. Scatchard analyses indicate that these changes likely involve both high- and low-affinity binding sites. The transitory reduction in [3H]MK801-binding after trauma may reflect downregulation of NMDA receptors as a consequence of posttraumatic glutamate release and may serve to limit excitotoxin-induced injury. PMID- 7889372 TI - A spectral analysis of the integration of artificial synaptic potentials in mammalian central neurons. AB - In order to simulate the interaction between synaptic input and intrinsic membrane properties in mammalian central neurons a well-defined current was injected into the neurons through a recording electrode. The stimulus was white noise bandpass filtered at 0.5 and 75 Hz and the power spectra of the responses were calculated. Recordings were obtained from neurons of the neocortex, the hippocampus, the thalamus and the cerebellar cortex. The neurons were either located in newly cut slices from adult guinea pig brains or in 3-10-weeks-old slice cultures from brains of newborn rats. In hippocampal and cortical cells the passive membrane properties dominated the shape of the power spectra. In general, when the average membrane potential was made more positive the power of the response increased. When neurons had active subthreshold responses like delayed rectification, sag-and-hump responses or delayed depolarization there was a depression of the response power at frequencies below 10-20 Hz. The depression was voltage dependent in the same way as the current that produced the active subthreshold response. In thalamic cells with a low-threshold Ca2+ spike (lts) the power of the responses grew in the 3-20-Hz range with hyperpolarization. The spectra of the responses of thalamic neurons had multiple peaks indicating multiple frequencies of resonance. Purkinje cells of the cerebellar cortex have prominent plateau potentials. When these cells were stimulated with the white noise at levels where the plateau potentials could be activated the spectra were dominated by a large peak at the lowest frequencies, i.e., below 5 Hz. Few cells in our data base generated spontaneous membrane potential oscillations. When the current stimulus was injected into such neurons the intrinsic rhythm was unaffected by the input and the power spectrum showed a marked peak at the frequency of the intrinsic oscillations. We conclude that bandpass filtered white noise as simulation of synaptic input is valuable for quantification of how passive and active membrane properties affect synaptic integration. The technique can also provide information on the role of transmitters and modulators in the CNS. PMID- 7889373 TI - Effect of corticosterone on the enhancement of the acoustic startle reflex by corticotropin releasing factor (CRF). AB - The present study evaluated the effects of adrenalectomy and chronic administration of corticosterone on the ability of CRF given intraventricularly to increase the amplitude of the acoustic startle reflex in rats. Experiment 1 showed that CRF-enhanced startle was not affected by adrenalectomy, indicating a central effect independent of the integrity of the hypothalamic-pituitary-adrenal axis. In Experiment 2, chronic injection of corticosterone augmented CRF-enhanced startle using a dose of CRF (0.25 micrograms) that normally is ineffective in increasing startle amplitude. Chronic injection of corticosterone by itself did not increase startle amplitude (Experiment 3). We suggest that the potentiation of CRF-enhanced startle by corticosterone may result from an activation of CRF in the central nucleus of the amygdala. PMID- 7889375 TI - Immunotherapy compliance--a shot in the dark? PMID- 7889374 TI - Progressive decrease in extracellular GABA concentrations in the post-ischemic period in the striatum: a microdialysis study. AB - Repetitive cerebral ischemia in gerbils produces delayed neuronal damage in the substantia nigra reticulata (SNr). This damage begins 4 to 5 days after the insult and is severe by day 7. The damage can be attenuated by GABA agonists. There is a prominent GABAergic striatal pathway to the SNr. Damage to this pathway leads to progressive loss of SNr neurons. This loss can be prevented by GABA agonists. We postulate that, ischemia-induced lack of GABAergic inhibitory input from the striatum to the SNr, may be responsible for this delayed neuronal damage. In the present experiment, we have measured striatal extracellular GABA concentrations with or without nipecotic acid, a GABA-reuptake inhibitor, in gerbils exposed to repetitive ischemia. GABA levels were measured on days 1, 3, 5, and 7 after the ischemic insult. Five control animals and a similar number of ischemic animals were monitored on each day. Extracellular fluid was collected using in vivo microdialysis and GABA levels were measured by electrochemical detection with HPLC. The extracellular striatal GABA levels were very low in the initial three specimens collected, both in the control and in the ischemic animals. However, addition of nipecotic acid resulted in an immediate increase of GABA in measurable range. In comparison to the controls, the increase in GABA on day 1 and 3 were significantly higher in animals with repetitive ischemia (two way ANOVA with repeated measures). Subsequent measurements showed a gradual decrease in GABA levels when compared to controls. The increase in GABA with nipecotic acid was significantly lower on day 7 after the ischemic insults when compared to the controls. The increased GABA responsiveness immediately after the ischemic insults may reflect a protective effect against excitotoxicity. The subsequent decline in GABA levels after the insult may be secondary to progressive loss of striatal GABAergic neurons. This may contribute to the production of delayed neural damage in the SNr by a decrease in the inhibitory striatal input. PMID- 7889376 TI - Hymenoptera, hypersensitivity, and history: a prologue to current day concepts and practices in the diagnosis, treatment, and prevention of insect sting allergy. PMID- 7889377 TI - Facial edema in a woman with a history of histiocytosis X. PMID- 7889378 TI - Manpower, quality care, ethics, and survival for allergists. PMID- 7889379 TI - Nasal patency in children with allergic rhinitis: correlation of objective and subjective assessments. AB - BACKGROUND: Children with allergic rhinitis may have difficulty with self assessment of nasal symptoms. OBJECTIVE: To correlate objective and subjective assessments of nasal stuffiness in children with seasonal allergic rhinitis. METHODS: Children, aged 6 to 12 years, with seasonal allergic rhinitis recorded their degree of nasal obstruction on two separate occasions using a nasal stuffiness score and a visual analogue scale. Physicians also assessed the degree of nasal obstruction using a visual analogue scale. Anterior rhinometry was performed and saccharin transient time was also measured. Correlations between subjective scores and objective measurements were calculated using Spearman correlation coefficients. RESULTS: Patient's nasal stuffiness scores correlated with their visual analogue assessment (r = .45, P = .0001). Patients visual analogue assessments did not correlate with anterior nasal airflow (r = -.12, P > .05). Physicians' visual analogue assessment correlated better with nasal airflow than childrens' assessment (r = -.41, P = .0001). Saccharin transit time was not helpful in assessment of degree of nasal obstruction. CONCLUSION: Children appear to have difficulty in self-assessment of nasal symptoms, and to be poor judges of the presence or severity of nasal obstruction. In studies of allergic rhinitis in children, objective measurements should be performed, if possible, to facilitate more accurate interpretation of data. PMID- 7889380 TI - Compliance with an allergen immunotherapy regime. AB - BACKGROUND: Compliance with an allergy immunotherapy regimen is obviously the difference between a potentially successful or unsuccessful outcome. OBJECTIVE: The purpose of this study was to assess retrospectively compliance of patients receiving immunotherapy in a private allergy practice. METHODS: The study evaluated retrospectively patient compliance with prescribed allergy injections for a private practice in Atlanta, Georgia. Patients who ordered allergy extract material for their injection immunotherapy program during an 18-month period served as the index population for this study. For the purposes of this study, noncompliance was defined as stopping the allergy injection program without the approval of the prescribing physician. Part of this investigation was to determine whether there were compliance differences between those who received their allergy injections within the confines of the clinic and those who received their injections at outside physician offices. A 12-month period of review was considered adequate to monitor compliance because of the 12-month expiration date placed on the allergy extracts. RESULTS: There was a noncompliance rate of 10: 77% for those who received their injections within the clinic. This contrasted with the noncompliance rate in the remote population of 34.82%. The difference between these two groups was statistically significant (P < .01). There were no statistical differences with respect to sex or diagnostic category. Significant differences were found between age groups in those receiving injections within or outside the clinic. CONCLUSIONS: There is a much higher rate of noncompliance in those who receive their injections in facilities outside the allergist's office. This suggests that to ensure better compliance either individuals should either be encouraged to receive their injections at the allergist's office, or better communications should be established between the referring allergist and the nonallergy physicians who are administering the injections. PMID- 7889381 TI - Production of diacylglycerol and arachidonic acid in peripheral blood mononuclear cells from patients with asthma and healthy controls. AB - BACKGROUND: Enhanced activities of peripheral blood cells are a common characteristic of patients with asthma. OBJECTIVE: Here we tested whether this could be due to a dysfunction in one or more signal transduction systems. METHODS: The production of 1,2-diacylglycerol (1,2-DAG) and arachidonic acid was compared in mononuclear blood cells from patients with asthma (n = 10) and healthy controls (n = 12). RESULTS: Using three different stimuli (concanavalin A, aluminium fluoride or the calcium ionophore A23187) no difference in the production of both 1,2-DAG and arachidonic acid could be found between patients and controls before allergen challenge. Concanavalin A-induced 1,2-DAG production could be inhibited completely in the presence of isoprenaline; concanavalin A induced arachidonic acid production, partially. The inhibitory effect of adenylate cyclase activation on the production of 1,2-DAG and arachidonic acid was identical in patients and controls. Following allergen challenge, there was a tendency to an increased production of 1,2-DAG and arachidonic acid in controls, whereas in patients there was a tendency to a decreased production. CONCLUSIONS: Enhanced cellular activities found in patients with asthma are not caused by an intrinsic dysfunction in production of 1,2-DAG and arachidonic acid. PMID- 7889382 TI - Induction of ICAM-1 expression on the eosinophilic leukemia cell line-3 (EoL-3) by platelet-activating factor and platelet factor 4. AB - BACKGROUND: Eosinophils are assumed to transmigrate to local tissue under the direction of the eosinophil chemotactic factor present in allergic inflammatory lesions. OBJECTIVE: We examined whether PAF and PF4, which are related to eosinophil localization, affect the expression of ICAM-1 on the human eosinophilic leukemia cell line (EoL-3). METHODS: ICAM-1 expression on EoL-3 cells in the presence or absence of PAF or PF4 was assessed by immunofluorescent analysis. The presence of sICAM-1 in culture supernatants of EoL-3 cells was detected with an ELISA kit. RESULTS: Both PAF and PF4 enhanced the expression of ICAM-1 on EoL-3 cells. We found no difference in sICAM-1 concentration with or without PAF or PF4. CONCLUSIONS: The eosinophil chemotactic factors PAF and PF4 not only may attract eosinophils, but they may enhance the expression of ICAM-1 on eosinophils at the site of the lesion. Further, it is suggested that the shedding of ICAM-1 has little relation to the induction of ICAM-1 expression in vitro. PMID- 7889383 TI - Measurement of mosquito Aedes vexans salivary gland-specific IgE and IgG antibodies and the distribution of these antibodies in human sera. AB - BACKGROUND: Lack of sensitive, reproducible, and specific immunoassays has hampered the evaluation and immunotherapy of mosquito allergy. OBJECTIVE: We wanted to develop ELISAs for measurement of mosquito-specific IgE and IgG using salivary glands from the mosquito Aedes vexans. METHODS: Microplates coated with the salivary gland antigen were sequentially incubated with serum samples or reference serum, goat antibody to human IgE or IgG, and enzyme-conjugated rabbit anti-goat IgG. RESULTS: The specificity of the assays was demonstrated by the successful inhibition of the ELISA reactions with the mosquito antigens. Reproducible results were obtained; mean coefficients of variation between assays were 0.200 +/- 0.002 for the IgE measurement and 0.114 +/- 0.001 for the IgG measurement. The sensitivity of each assay was 0.39 U/mL. Using these assays, sera from 50 subjects with skin reactions to mosquito bites ranging from negative to strongly positive were analyzed for mosquito-specific IgE and IgG. The mean mosquito-specific IgE and IgG were significantly higher in subjects with skin reactions to mosquito bites than in those without skin reactions (P < .005), higher in females than males (P < .031), and slightly higher in atopics than nonatopics (P > .05). Also, there was a significant correlation between mosquito specific IgE and IgG levels (r = .77, P < .001). CONCLUSIONS: Specific, reproducible, and sensitive ELISAs have been developed for measurement of antibodies to Aedes vexans. Mosquito-specific IgE and IgG may involved in the development of sensitivity to mosquito bites. PMID- 7889384 TI - Home health care costs: intravenous immunoglobulin home infusion therapy. AB - BACKGROUND: Home health care has been touted as a cost-saving option for many immune disorders, especially those requiring intravenous immunoglobulin (IVIG). OBJECTIVE: To determine the costs for home infusions of IVIG, a comparative study of Home Health Agency prices was undertaken. METHOD: A survey of 25 Home Health Agencies that provide IVIG therapy in northern and central New Jersey was conducted by telephone and office interviews. RESULTS: Thirteen companies provided price quotations for services and IVIG. The highest-priced companies charge approximately four times more for IVIG infusions than the lowest-priced companies, and many agencies offer the therapy at moderate costs. CONCLUSION: IVIG can be obtained and administered in the home in more cost-effective ways if comparative pricing is done. PMID- 7889385 TI - Air quality and the frequency of emergency room visits for asthma. AB - BACKGROUND: Atmospheric pollution has been proposed as one of the possible factors responsible for increases in asthma mortality and morbidity. OBJECTIVE: We sought to examine whether we could demonstrate a relationship between emergency room visits for asthma and alterations in environmental conditions. METHODS: Over a 1-year period, the frequency of emergency room visits for asthma in a large urban hospital were documented and compared to outdoor concentrations of SO2, NO2, and ozone in addition to two overall measures of air quality (air pollution index and air quality index). RESULTS: A total of 854 emergency room visits were noted with the highest number of visits occurring in May and between September and December. Significant variations in the frequency of visits as well as environmental conditions could be seen on a daily basis. Despite comparisons of results on a daily, weekly, and monthly basis, no significant relationships could be found between any of the pollution indices and emergency room visits. Staggering visits by 1 and 7 days, however, revealed a relationship between emergency room visits and air pollution index and air quality index. An association between emergency room visits and NO2 and ozone was seen when visits were staggered by 7 but not by 1 day. CONCLUSIONS: We conclude the fluctuations in overall air quality are associated with increased frequency of emergency room visits but only when data are lagged by a predefined period. PMID- 7889386 TI - Sampler calibration. PMID- 7889388 TI - Role of food allergy in serous otitis media. PMID- 7889387 TI - Efficacy of sublingual immunotherapy not established. PMID- 7889389 TI - Clinical highlights from the National Cancer Data Base: 1995. AB - The National Cancer Data Base, a joint project of the American Cancer Society and the American College of Surgeons Commission on Cancer, provides a mechanism for periodic assessment of hospital-based cancer patient care. From the National Cancer Data Base's annual summary, health care professionals can evaluate trends in patient care to make more efficient treatment decisions. This article provides a first look at highlights of the 1995 annual summary. PMID- 7889390 TI - Advocating for the woman with breast cancer. AB - Health care workers and breast cancer survivors have an important role to play as advocates for breast cancer patients. At the most basic level, advocates must ensure that the patient has access to medical care. In addition they must help to ensure that the quality of care is optimal, enhancing the likelihood of survival, rehabilitation, and psychological adaptation. This article describes important advocacy issues for women with breast cancer, including informational needs, patient-physician communication, choice of primary surgical treatment, reconstructive surgery, adjuvant therapy, psychosocial issues, and employment and insurance problems. PMID- 7889392 TI - Early detection of ovarian cancer. AB - Ovarian cancer meets the criteria of a disease for which screening can be justified. The disease is most often diagnosed in advanced stages, when chances for long-term survival are poor. Yet effective treatment exists for early-stage disease, such that early detection can increase long-term survival. However, screening for early-stage ovarian cancer with the high specificity necessary for this low-prevalence disease has proven to be a challenge. This article reviews the issues of early detection of ovarian cancer, including pathology, statistical considerations, diagnostic modalities, and results of the major clinical studies undertaken. PMID- 7889391 TI - Ovarian cancer. PMID- 7889393 TI - The treatment of epithelial ovarian cancer. AB - The treatment and long-term survival of patients with ovarian cancer varies by stage. At present, five-year survival for patients with early-stage disease ranges from 50 to 95 percent, while five-year survival for patients with advanced stage disease is less than 25 percent. Several new drugs with significant activity in advanced-stage ovarian cancer offer hope for increased long-term survival in the future. This article reviews the current and experimental approaches to the treatment of all stages of ovarian cancer. PMID- 7889394 TI - Kinetics and affinity of reactions between an antigen-specific T cell receptor and peptide-MHC complexes. AB - We show here that the net rate of accumulation of complexes formed by the antigen specific receptor of T cells (TCR) of a T cell clone with its natural ligand, an octapeptide in association with Ld, a class I protein of the major histocompatibility complex (MHC), approaches the maximal value determined by the affinity of the TCR for this peptide-MHC ligand in 1-2 min, which is well within the lifetime of transient T cell-target cell conjugates. Consistent with this finding, we also found that the widely divergent affinity values (equilibrium constants) of this TCR for six related peptide-MHC complexes correlate well with the extent of specific lysis of target cells bearing various level of these complexes. PMID- 7889395 TI - Processing and major histocompatibility complex binding of the MTV7 superantigen. AB - Mouse mammary tumor viruses produce superantigens (vSAGs) which interact with class II major histocompatibility complex (MHC) proteins and stimulate T cells. vSAGs are synthesized as Type II membrane proteins, but at least one of these proteins (vSAG7) is found on the cell surface in a proteolytically processed form. Monoclonal antibodies (MAbs) were used to characterize vSAG7 and its binding to class II molecules. vSAG7 is synthesized in the endoplasmic reticulum (ER) as a 45 kd glycoprotein containing N-asparagine-linked oligomannosyl carbohydrates. vSAG7 transits the golgi complex, where it is modified by the addition of complex-type glycans and proteolysed at three positions. After proteolysis, the amino and carboxyl termini remain noncovalently associated. The ER, golgi, and surface forms of vSAG7 are stably bound to class II, but one of the proteolysed forms comprises the majority of the class II-bound material. PMID- 7889396 TI - Thymic selection: two pathways to life and two to death. PMID- 7889397 TI - Evidence for a superantigen in human tuberculosis. AB - T cells are not only required for resistance to tuberculosis, but they likely contribute to the tissue damage characteristic of the disease. To define better the T cell populations that contribute to the immunopathogenesis of human tuberculosis, we investigated the T cell receptor (TCR) beta chain repertoire expressed in patients with tuberculous pleuritis. Analysis by polymerase chain reaction and flow cytometry indicated an expansion of V beta 8+ T cells at the site of disease in some donors, suggesting the possibility that Mycobacterium tuberculosis contains a superantigen. M. tuberculosis induced strong T cell proliferative responses in tuberculin-negative healthy donors in vitro, with preferential expansion of V beta 8+ T cells, independent of the CDR3 region. T cell stimulation was MHC class II-dependent and did not require antigen processing by the antigen-presenting cells. These findings are consistent with the presence of a superantigen in M. tuberculosis, aspects of which may contribute to the immunopathology of tuberculosis and to the adjuvant properties of M. tuberculosis. PMID- 7889398 TI - Intracellular signals that mediate thymic negative selection. AB - Antigenic stimulation of CD4/CD8 double positive (DP) thymocytes results in programmed cell death, while the identical stimulation of mature T cells results in proliferation and lymphokine secretion. Using thymocytes from transgenic mice expressing pigeon cytochrome c-specific T cell receptors, we previously demonstrated that major histocompatibility complex class II-transfected L cells were capable of presenting peptide antigen and inducing programmed cell death in DP thymocytes, as well as proliferation and lymphokine secretion in mature CD4 single positive (SP) T cells. We therefore were interested in utilizing this system to compare antigen-induced signal transduction events in DP thymocytes and mature SP T cells. In this report, we demonstrate that significant distinctions between thymocytes and mature T cells are seen upon examination of antigen sensitivity and the phosphatidylinositol signaling cascade. PMID- 7889399 TI - Porcine aortic endothelial cells activate human T cells: direct presentation of MHC antigens and costimulation by ligands for human CD2 and CD28. AB - We examined the human xenoresponse to cultured porcine aortic endothelial cells (PAECs). Human CD8+ T cells proliferate to resting MHC class I-positive PAECs. CD4+ T cells proliferate after MHC class II molecules are induced with swine interferon-gamma. These responses are greater than corresponding allogeneic responses to human umbilical vein endothelial cells (HUVECs). Limiting dilution analysis shows a 10-fold higher frequency of xenoreactive than alloreactive anti endothelial lymphocytes. Species-specific monoclonal antibodies suggest that PAECs directly present swine MHC antigens to human T cells and that human CD4 and CD8 molecules participate in this interaction. Furthermore, PAECs bind CTLA-4-Ig and costimulate human T cells by both the CD2 and CD28 pathways. In contrast, HUVECs do not bind CTLA-4-Ig and only use the CD2 pathway. PMID- 7889400 TI - Generation of normal T and B lymphocytes by c-jun deficient embryonic stem cells. AB - To determine the potential roles of c-jun in lymphocyte development, we generated somatic chimeric mice by injecting homozygous c-jun mutant embryonic stem (ES) cells into blastocysts from recombination activating gene-2 (RAG-2)-deficient mice. Chimeric mice had poor restoration of thymocytes, but contained substantial numbers of mature T and B lymphocytes in the periphery. Stimulation of c-jun-/- B cells resulted in normal levels of proliferation and immunoglobulin secretion. Likewise, stimulation of c-jun-/- T cells resulted in essentially normal levels of IL-2R alpha expression, IL-2 secretion, and proliferation. We further showed that the relatively normal activation responses of the c-jun-/- T cells probably results from the fact that other members of the Jun family contribute to the bulk of the activator protein-1 (AP-1) complexes in normal T cells and, as a result, AP-1 complexes are found at relatively normal levels in c-jun-/- T cells. PMID- 7889401 TI - Human transporters associated with antigen processing possess a promiscuous peptide-binding site. AB - The peptide selectivity of the human transporters associated with antigen processing (TAP) was investigated using a panel of peptides of varying length and sequence. Peptides were assayed for their ability to compete for the translocation of a labeled reporter peptide containing an N-linked glycosylation acceptor site in Streptolysin O (SLO)-permeabilized cells. We find that human TAP is very promiscuous for peptides in the 8-12 amino acid range, while showing increased selectivity and lower translocation efficiency for peptides in the 13 30 amino acid range. The minimum peptide length appears to be 8 amino acids, while the maximum length appears to be approximately 25 amino acids. Furthermore, a photoactive peptide analogue was synthesized that can photolabel TAP molecules. Using this analogue, we showed that an ATP-independent peptide-binding site exists on TAP, and that competition for translocation reflects competition for peptide binding. PMID- 7889402 TI - A role for non-MHC genetic polymorphism in susceptibility to spontaneous autoimmunity. AB - Peripheral immunological tolerance is traditionally explained by mechanisms for deletion or inactivation of autoreactive T cell clones. Using an autoimmune disease model combining transgenic mice expressing a well-defined antigen, influenza hemagglutinin (HA), on islet beta cells (Ins-HA), and a T cell receptor transgene (TCR-HNT) specific for a class II-restricted HA peptide, we demonstrate that the conventional assumptions do not apply to this in vivo situation. Double transgenic mice displayed either resistance or susceptibility to spontaneous autoimmune disease, depending on genetic contributions from either of two common inbred mouse strains, BALB/c or B10.D2. Functional studies on autoreactive CD4+ T cells from resistant mice showed that, contrary to expectations, neither clonal anergy, clonal deletion, nor receptor desensitization was induced; rather, there was a non-MHC-encoded predisposition toward differentiation to a nonpathogenic effector (Th2 versus Th1) phenotype. T cells from resistant double transgenic mice showed evidence for prior activation by antigen, suggesting that disease may be actively suppressed by autoreactive Th2 cells. These findings shed light on functional aspects of genetically determined susceptibility to autoimmunity, and should lead to new therapeutic approaches aimed at controlling the differentiation of autoreactive CD4+ effector T cells in vivo. PMID- 7889403 TI - Isoforms of the transmembrane tyrosine phosphatase CD45 differentially affect T cell recognition. AB - Activation of T cells has been shown to require CD45. CD45 is expressed on T cells as distinct isoforms and these isoforms are expressed differentially on subsets of CD4 T cells. We have generated T cell lines expressing a T cell receptor (TCR) of known specificity, with or without CD4, and examined the effect of different CD45 isoforms on stimulation through the antigen receptor. We find that isoforms differ in their ability to participate in antigen recognition, with the null isoform that is predominantly found on memory CD4 T cells being the most effective. The ability of the CD4 T cells being the most effective. The ability of the CD45 ectodomain to differentially affect sensitivity to specific ligands represents a novel way of regulating the efficacy of signaling through a receptor without altering its specificity. It may play a crucial role both in immunological memory and during intrathymic maturation of T cells. PMID- 7889405 TI - The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster. AB - The gene for the mouse Fas ligand was cloned and its chromosomal position determined. Fasl was tightly linked to gld (no crossovers in 567 meiotic events) on mouse chromosome 1 and closely linked with a novel member of the same TNF family of ligands, the Ox40 ligand (Ox40l, 1 crossover in 567 meiotic events). Southern blot analysis did not reveal any difference between the Fasl gene from gld and wild-type mice and levels of Fasl mRNA transcripts were similar in PMA and ionomycin induced wild-type and coisogenic gld T cells. Sequence analysis of the gld gene indicated a single amino acid change (Phe Leu) in the COOH terminal portion of this type II transmembrane protein, and COS cells transfected with Fasl cDNA from gld mice failed to induce apoptosis of Fas-expressing target cells. Thus, the data demonstrate that the gld phenotype is the result of a point mutation in the Fasl gene and that Fasl is part of a complex of ligands structurally related to TNF mapping within a small region of mouse chromosome 1. PMID- 7889406 TI - Induction of NF-AT in normal B lymphocytes by anti-immunoglobulin or CD40 ligand in conjunction with IL-4. AB - We show here that ligation of surface immunoglobulin or CD40 receptors in conjunction with interleukin-4 induces the nuclear factor of activated T cells (NF-AT) in normal murine B cells, which is inhibited by cyclosporin (CsA). Lipopolysaccharide, which activates B cells by a Ca(2+)-independent, CsA resistant pathway, does not induce NF-AT. The NF-AT complex in T cells and B cells appears to be identical, comprising both Fos and Jun proteins and the 120 kDa cytosolic component of NF-AT (NF-ATp). Our transfection experiments using a trimerized NF-AT site linked to the minimal IL-2 promoter driving luciferase activity demonstrate that NF-AT is functional in A20 B-lymphoma cells. These results therefore suggest that the induction of NF-AT forms part of the B cell response to both cross-linking antigens and T cell-generated signals. PMID- 7889404 TI - Differences in peptide presentation between B27 subtypes: the importance of the P1 side chain in maintaining high affinity peptide binding to B*2703. AB - Susceptibility to spondyloarthropathies is strongly associated with the MHC class I molecule HLA-B27, and is hypothesized to result from the presentation of arthritogenic peptides. Subtypes of B27 that differ structurally but are disease associated ought to be capable of presenting such peptides, while nondisease associated subtypes would not. We demonstrate that B*2703, the predominant West African B27 subtype that may not predispose to disease, is not recognized by most B*2705-alloreactive CTL, and does not efficiently present a known B*2705 restricted influenza A nucleoprotein (NP) peptide. We show inefficient presentation is due to a reduced binding affinity of B*2703 for the NP peptide. Furthermore, substituting Arg for the naturally occurring Ser at P1 of the NP peptide, restores high affinity binding and efficient presentation by B*2703. Our results suggest that B*2703 will bind and present efficiently only a subset of the peptides that bind to B*2705, in particular those with Arg or Lys at P1. The apparent lack of disease in individuals with B*2703 may be due to an inability to bind and present putative arthritogenic peptides. PMID- 7889407 TI - Cyclosporin-A sensitive induction of NF-AT in murine B cells. AB - Primary B cells are induced to proliferate by cross-linking surface immunoglobulin or by its pharmacological equivalent, phorbol ester and calcium ionophore. However, nuclear responses that have been studied in activated B cells are typically inducible with phorbol esters alone. We show that a factor, indistinguishable from the nuclear factor of activated T cells (NF-AT), is induced in B cells in response to anti-immunoglobulin signals or the combined action of phorbol ester and ionomycin, but not in response to either reagent alone. The signals necessary for NF-AT induction in B cells, therefore, closely parallel those required to induce B cell proliferation. Transfection analysis shows that B cell NF-AT is a transcriptional activator. Furthermore, NF-AT induction in splenic cells is suppressed by cyclosporin A, suggesting a mechanism by which immunosuppressive agents act on the B cell compartment. We propose that NF-AT should be considered more generally as a nuclear factor of activated lymphoid cells. PMID- 7889409 TI - A locus control region in the T cell receptor alpha/delta locus. AB - A locus control region (LCR) is a set of cis-acting elements that regulate chromatin accessibility of a gene locus. In the T cell receptor (TCR) alpha/delta locus, an LCR might regulate the differential tissue and developmental expression and the rearrangement of TCR alpha and delta genes. We have localized a region 3' of the TCR alpha/delta locus containing eight T cell-specific nuclease hypersensitive domains (HS-1 to HS-8), which fit the characteristics of an LCR. In transgenic mice, a TCR alpha gene linked to this region is expressed at a high level, independent of the site of integration and correlates with gene copy number. The transgene is expressed in the alpha beta but not the gamma delta T cell subset and is activated at the right time during development. Proper LCR function requires the region containing HS-2 to HS-6. We propose a model of LCR competition to explain the differential regulation of TCR alpha versus delta genes during development. PMID- 7889408 TI - Bcl-2 is upregulated at the CD4+ CD8+ stage during positive selection and promotes thymocyte differentiation at several control points. AB - In vivo thymocyte maturation models were used to investigate the differentiation role of Bcl-2. In alpha/beta T cell receptor (TCR) class II-restricted transgenic mice, Bcl-2 was upregulated at the CD4+ CD8+ stage during positive selection. The lckpr-bcl2 transgene was bred onto MHC classes I-I- and II-I-, MHC-I-, and alpha/beta TCR backgrounds to determine whether Bcl-2 promoted thymocyte maturation in the absence of coreceptor-MHC interaction. Bcl-2 rescued CD8+ thymocytes in class I-I- and alpha/beta TCR in mice; however, they were not exported to the periphery. Bcl-2 had no effect on CD4 lineage maturation in class II-I- mice. No single-positive thymocytes accumulate in MHC-I- mice despite overexpressed Bcl-2. Thus, Bcl-2 enables selection of certain TCRs on class II molecules and their differentiation along the CD8 pathway; however, Bcl-2 did not substitute for positive selection. In RAG-1-I- mice, Bcl-2 promoted differentiation to the CD4+ CD8+ stage. Bcl-2 can promote thymocyte maturation at several control points. PMID- 7889410 TI - Polygenic control of susceptibility to murine systemic lupus erythematosus. AB - Susceptibility to glomerulonephritis (GN) and anti-dsDNA autoantibody production was analyzed in crosses with a newly developed systemic lupus erythematosus susceptible inbred strain, NZM/Aeg2410. The mode of inheritance and the number and location of systemic lupus erythematosus-associated susceptibility loci were analyzed by interval mapping in a backcross with C57BL/6. Three chromosomal intervals containing strong recessive GN susceptibility alleles were identified on chromosomes 1, 4, and 7, each containing several potentially interesting candidate genes. Heterozygosity at H-2 was also found to correlate strongly with GN susceptibility, consistent with previous findings in the NZB/NZW parental strain model. Logistic regression analysis indicated that each of these susceptibility alleles independently accounted for a component of GN susceptibility, and that susceptibility was inherited as a threshold genetic liability in this model system. PMID- 7889411 TI - How virus induces a rapid or slow onset insulin-dependent diabetes mellitus in a transgenic model. AB - We developed two distinct transgenic mouse models in which virus induced insulin dependent (type 1) diabetes mellitus (IDDM). In one of these lines, the unique viral transgene was expressed in the islets of Langerhans and also in the thymus, but in the other line, expression was only in the islets. Insertion and expression of the viral (self) gene, per se, did not lead to IDDM, (incidence < 5%). By contrast, induction of an anti-self (anti-viral) CD8+ CTL response to the same virus later in life caused IDDM (incidence < 90%) in both transgenic lines, although the kinetics and requirements for CD4 help, the affinity and avidity of CD8+ CTL differed in each line. Mice not expressing the viral (self) gene in the thymus developed IDDM 10-14 days after infection. CD4+ T cells played no detectable role, since their depletion failed to alter either the kinetics or incidence of IDDM. By contrast, mice that expressed the viral gene in the thymus required significantly more time to develop IDDM. Their anti-self (viral) CD8+ CTL were of lower affinity and avidity than CD8+ CTL generated by nontransgenic controls. Disease was dependent on T cell help, since deletion of CD4+ cells completely circumvented the IDDM. PMID- 7889412 TI - The CD8 coreceptor revisited: one chain good, two chains better. PMID- 7889413 TI - An activated lck transgene promotes thymocyte development in RAG-1 mutant mice. AB - Expression of the T cell receptor beta (TCR beta) chain is necessary for the transition from the CD4CD8- stage in the major alpha beta thymocyte lineage. The protein tyrosine kinase p56lck has been implicated in the regulation of early thymocyte differentiation and of allelic exclusion at the TCR beta locus. Using mice overexpressing an activated lck transgene and mice with a disruption of the lck gene, we demonstrate that p56lck participates in a pathway that regulates the expansion of the pool of CD4+CD8+ thymocytes to wild-type levels. In addition, p56lck may be involved in the down-regulation of the putative pre-TCR on CD4+CD8+ thymocytes. PMID- 7889414 TI - Functional commitment to helper T cell lineage precedes positive selection and is independent of T cell receptor MHC specificity. AB - Thymocyte differentiation proceeds from double positive CD4+CD8+ to single positive T cells. It has been proposed that this process occurs by an instructive or a stochastic mechanism. In this report, we show that in recombination deficient mice (RAG-1-I-) constitutive expression of a CD8 transgene allows maturation of CD4+(CD8tg+) cells, which express mature levels of a transgenic class I-restricted T cell receptor, F5. Rescued F5+CD4+(CD8tg+) cells have equivalent levels of T cell receptor expression as CD8end+ cells, respond to cognate antigen and, upon stimulation, they exhibit a phenotype characteristic of CD4+ helper T cells. These data are consistent with a model of differentiation that predicts that thymocytes become functionally committed to a helper or cytotoxic lineage before the final step of positive selection and independently of MHC specificity of their T cell receptor. PMID- 7889415 TI - Disruption of T lymphocyte positive and negative selection in mice lacking the CD8 beta chain. AB - The CD4 and CD8 coreceptors have been shown to play significant roles in the differentiation and activation of helper and cytotoxic T lymphocytes (CTLs), respectively. Coordinate binding of coreceptor and T cell receptor (TCR) to the same major histocompatibility complex (MHC) molecule and coreceptor interaction with the tyrosine kinase p56lck are required for effective signaling. Whereas CD4 is a monomer, CD8 consists of either alpha alpha homodimers or alpha beta heterodimers. Signaling properties of CD8 have been ascribed to the alpha chain, which binds to both the MHC class I and to p56lck, respectively. To study CD8 beta specifically, we have generated mice defective in its expression. We observe a significant reduction in the numbers of CD8+ T cells, but these cells have normal CTL activity. By breeding CD8 beta null mice with animals expressing a class I-specific TCR transgene, we show that CD8 beta plays a significant role in both positive and negative selection of developing thymocytes. PMID- 7889416 TI - A role for the cytoplasmic tail of the beta chain of CD8 in thymic selection. AB - The CD8 coreceptor plays a critical role in the recognition of foreign antigens by mature T cells and in the development of class I-restricted T cells. CD8 can be expressed on the surface of T cells as either a heterodimer composed of an alpha and beta chain, or as a homodimer composed of two alpha chains. In this report, we show that a CD8 beta transgene that lacks a cytoplasmic domain can suppress expression of wild-type endogenous CD8 beta and act as a dominant negative mutation. We show that this dominant negative CD8 beta transgene interferes with the development of mature CD8 T cells to different extents depending on the individual class I-restricted TCR. These data suggest CD8 beta plays a role in thymic development, and that different class I-restricted TCRs differ in their dependence on the cytoplasmic tail of CD8 beta. PMID- 7889417 TI - Development of hematopoietic stem cell activity in the mouse embryo. AB - The precise time of appearance of the first hematopoietic stem cell activity in the developing mouse embryo is unknown. Recently the aorta-gonad-mesonephros region of the developing mouse embryo has been shown to possess hematopoietic colony-forming activity (CFU-S) in irradiated recipient mice. To determine whether the mouse embryo possesses definitive hematopoietic stem cell activity in the analogous AGM region and to determine the order of appearance of stem cells in the yolk sac, AGM region, and liver, we transferred these embryonic tissues into adult irradiated recipients. We report here the long-term, complete, and functional hematopoietic repopulation of primary and serial recipients with AGM derived cells. We observe potent hematopoietic stem cell activity in the AGM region before the appearance of yolk sac and liver stem cell activity and discuss a model for the maturation of stem cell activity in mouse embryogenesis. PMID- 7889418 TI - Investigation of the interaction between the class I MHC-related Fc receptor and its immunoglobulin G ligand. AB - The neonatal Fc receptor (FcRn) is structurally similar to class I major histocompatibility molecules. FcRn transports maternal immunoglobulin G (IgG) from ingested milk into the blood. IgG is bound at the pH of milk (pH 6.0-6.5) in the gut and released at the pH of blood (pH 7.5). We find that alteration of a histidine pair within the alpha 3 domain of FcRn and of a nearby loop (the FcRn counterpart of the class I CD8-binding loop) affects the affinity for IgG. Inhibition studies suggest the involvement of the FcRn B2-microglobulin domain in IgG binding. Fragment B of protein A inhibits FcRn binding to IgG, localizing the binding site on Fc for FcRn to the CH2-CH3 domain interface. Three histidines present at the CH2-CH3 domain interface of Fc could be partially responsible for the pH-dependent interaction between FcRn and IgG. PMID- 7889419 TI - Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo. AB - An adoptive transfer system was used to monitor physically the behavior of a trace population of TCR transgenic T cells in vivo. After subcutaneous injection of antigen in adjuvant, the antigen-specific cells accumulated first in the paracortical region of the draining lymph nodes, proliferated there for several days, and then moved into lymph node follicles, where they accounted for most of the T cells. They then disappeared slowly from the draining nodes, and the remaining cells were hypersensitive to antigenic stimulation in vitro. In contrast, when the antigen was introduced into the blood, the antigen-specific cells rapidly accumulated in the paracortical regions of all lymph nodes, proliferated there for a short time, but never entered follicles. Most of the cells then rapidly disappeared, leaving behind a population that was hyporesponsive to antigenic stimulation. These results provide a physical basis for the classical finding that antigen-specific memory and tolerance can be influenced by the form of antigen administration. PMID- 7889420 TI - Oilseed rape and seasonal symptoms. PMID- 7889421 TI - Allergen-antibody complexes in the treatment of Dermatophagoides pteronyssinus hypersensitivity diseases. PMID- 7889422 TI - Activation and inhibition of mediator release from skin mast cells: a review of in vitro experiments. PMID- 7889423 TI - The identification of potential aeroallergen/irritant(s) from oilseed rape (Brassica napus spp. oleifera): volatile organic compounds emitted during flowering progression. AB - Volatile organic compounds emitted by growing intact oilseed rape plants have been detected using an entrainment apparatus enabling volatile headspace analysis by thermal desorption coupled to capillary gas chromatography-mass spectrometry. In total, 22 volatile compounds were identified as being emitted during the flowering period. The main constituents were alpha-farnesene (a sesquiterpene); beta-myrcene (a monoterpene); linalool (a monoterpene alcohol) and the 'green leaf' volatile (E)-3-hexen-1-ol acetate. These compounds constituted between 50 and 87% (mean 68%) of the total volatiles emitted in all of the entrainments carried out with flowering oilseed rape plants. The remaining constituents consisted of a range of compounds including other terpenoids, the characteristic 'green leaf' volatile (E)-3-hexen-1-ol, short chain alcohols and ketones, organic sulphides and nitrogen-containing compounds. These were generally present as minor constituents but some plant entrainments revealed that higher relative amounts could be emitted. This was particularly apparent for dimethyl disulphide, 3-methyl-2-pentanone, 3-hydroxy-2-butanone, sabinene, isomyrcenol and (E)-3-hexen 1-ol. The possible role of the 22 compounds in respiratory mucosa and conjunctiva irritation associated with airborne releases from oilseed rape is discussed. PMID- 7889424 TI - The anaphylaxis hypothesis of sudden infant death syndrome (SIDS): mast cell degranulation in cot death revealed by elevated concentrations of tryptase in serum. AB - A series of cases of sudden unexpected post-neonatal deaths from two centres in the UK have been investigated for evidence of mast cell activation using the biochemical markers tryptase and 9 alpha,11 beta-PGF2. Tryptase was selected as a possible marker because it is a component of mast cell secretory granules and, unlike histamine, it is not released from basophils. The prostaglandin 9 alpha,11 beta-PGF2 is an initial and pharmacologically active metabolite of PGD2, the major mast cell-derived cyclooxygenase product. This prostaglandin was chosen to serve as a marker of newly generated mediator release. In the study, unexplained infant deaths were associated with a higher concentration of tryptase in serum compared with cases of unexpected, but subsequently explained death. However, 9 alpha,11 beta-PGF2 was found to be an unsuitable post mortem marker in this situation. These results provide direct evidence that mast cell degranulation, possibly as a result of anaphylaxis, may be occurring around the time of death in some cases of cot death. PMID- 7889425 TI - Seasonal asthma caused by airborne Platanus pollen. AB - This work describes three patients suffering from bronchial asthma after being naturally exposed to airborne plane-tree pollen. The three patients gave immediate response in skin tests and dual response in bronchial provocations using Platanus hybrida extract. There was specific seric IgE activity against this/these antigen(s) with the CAP system. The three patients also showed significant correlation (P < 0.001) between their rhinitis and asthma symptom scores registered on their diary cards and plane-tree pollen counts, collected using the Burkard spore trap. Among 187 patients living in Madrid and who came to our centre with a history of rhinitis and/or seasonal asthma, we found a prevalence of positive skin-prick tests to Platanus of 56%, only surpassed by gramineous pollen (Dactylis glomerata and/or Trisetum paniceum) 92% and Olea europaea 63%. The aerobiological sampling of the pollen content of the air in Madrid, carried out between 1 January 1979 and 31 December 1993 revealed an airborne presence (per cent of total yearly pollen count, mean of 1979-1993) of 14.9% for the Platanus, 14.8% for grasses, 9.8% for Olea and 3.6% for Plantago. The Platanus is one of the most frequently found pollens in the atmosphere over Madrid. At present, in this geographical area, a high percentage of patients with pollinosis are sensitive to this pollen. At least in some of these patients Platanus pollen is capable of inducing rhinitis and bronchial asthma. PMID- 7889427 TI - Cow milk allergy within the spectrum of atopic disorders. AB - In order to examine the relationship between cow milk allergy (CMA) and atopic disorders in childhood, a consecutive group of 42 infants with IgE mediated CMA was followed for at least 2 years. The incidence of sensitization to common food and inhalant antigens and the development of eczema, asthma, and food allergies was examined for the cohort and compared between patients whose CMA remitted and those with persistent disease. In this cohort the prevalence of eczema was 57%, asthma 69%, egg allergy 67%, peanut allergy 55%, and 83% of infants demonstrated positive skin-prick tests to three or more allergens. At the end of the study CMA had remitted in 13 patients (median age 44 months) whereas in 29 patients it persisted (median age 44 months). Although there was no significant difference in the incidence of eczema or asthma during the study between these two patient groups, the incidence of allergy to egg and peanut butter was significantly greater for children with persistent CMA. Consistent with our hypothesis that children with persistent CMA have a more severe dysregulation of IgE synthesis than those whose disease remits, patients with persistent CMA had a significantly higher incidence of and level of skin sensitivity to inhalant and other dietary allergens. Sensitization to the inhalant allergens Dermatophagoides pteronyssinus, cat dander and rye grass was frequently seen in early infancy and increased during the study period. Thus, children with IgE mediated CMA frequently generate IgE responses to multiple dietary and inhalant allergens in infancy and early childhood and develop immediate hypersensitivity to other foods as well as clinical eczema, and asthma. PMID- 7889426 TI - The prevalence of childhood asthma in Costa Rica. AB - The prevalence of asthma in children between the ages of 5 and 17 years in Costa Rica was determined using a large sample (n = 2682). The definition of asthma was based on a combination of a physician's diagnosis and a symptom score, using information from a questionnaire given to the parents. An overall asthma prevalence as high as 23.4% was found. Sex, age, urban/rural location, or rain precipitation did not show any association with the diagnosis of asthma. The presence of smokers in the home was found to be an important risk factor (odds ratio = 1.6). Another identified risk factor was a high yearly average outside temperature, i.e. above 25 degrees C (odds ratio = 1.8). Furthermore, the proportion of children with more than four upper respiratory infections during the preceding year was found to be significantly increased in children with asthma (odds ratio = 4.3). The non-asthma group seemed to use equal amounts of drugs for the treatment of asthma as the asthma group. For a country like Costa Rica with limited economic resources the current work indicates two important issues for consideration in the future; firstly, to try to define the cause(s) of asthma and secondly, to continuously inform the physicians about the best way of diagnosing and treating asthmatic patients to ensure optimal handling of this large patient group. PMID- 7889428 TI - A double-blind comparison of fluticasone propionate aqueous nasal spray, terfenadine tablets and placebo in the treatment of patients with seasonal allergic rhinitis to grass pollen. AB - Fluticasone Propionate Aqueous Nasal Spray (FPANS) contains a topically active glucocorticoid fluticasone propionate which has been used successfully for the treatment of seasonal allergic rhinitis. This multicentre, randomized, double blind, double-dummy, placebo-controlled, parallel group study was designed to compare the efficacy and tolerability of FPANS with terfenadine tablets or placebo in controlling the symptoms of allergic rhinitis to grass pollen. Two hundred and fourteen patients were treated for 6 weeks during the grass pollen season with either FPANS 200 micrograms once daily, terfenadine tablets (60 mg) twice daily or placebo. Efficacy was evaluated by the analysis of symptom-free days and median symptom scores. Patients receiving FPANS had significantly more days free of nasal blockage on waking (P = 0.012) and during the day (P = 0.01) and of rhinorrhoea (P = 0.027) than those receiving terfenadine. Additionally, in terms of absolute efficacy, patients receiving FPANS demonstrated significantly more days free of the above symptoms (P = 0.017, P = 0.028, P = 0.004, respectively) and of sneezing (P < 0.001) than those receiving placebo. There were no significant differences in symptoms of nasal itching, eye symptoms, of symptoms of drowsiness between the three treatment groups. Patients in the FPANS group had significantly lower median symptom scores for nasal blockage on waking (P < 0.001) and during the day (P < 0.018) than those in the terfenadine group and significantly lower scores for nasal blockage on waking (P < 0.001), sneezing (P < 0.013) and rhinorrhoea (P = 0.005) than those in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889429 TI - Eosinophil inflammation of the nasal mucosa in allergic and non-allergic rhinitis measured by eosinophil cationic protein levels in native nasal fluid and serum. AB - Eosinophil inflammation is essential in many cases of allergic and non-allergic rhinitis. Activated eosinophils release toxic granule proteins. In this study, we compared the degree of local nasal and systemic eosinophil activation by the determination of eosinophil cationic protein (ECP) in serum and native nasal fluid from 119 patients. We found no significant differences in serum ECP levels of the various patient groups. In all patient groups, except in the vasomotor rhinitis group, nasal fluid ECP levels differed significantly from normal controls. We found a nasal fluid ECP (mean +/- SEM) of 32.6 +/- 8.1 ng/ml for normals, 106 +/- 39.7 for non-rhinitic atopics, 87.6 +/- 20.8 ng/ml for patients with chronic non-allergic sinusitis, 101.3 +/- 40.4 ng/ml for patients with a history of pollinosis, 150.5 +/- 35.1 ng/ml for patients with acute pollinosis, 84.7 +/- 24.7 ng/ml for individuals with perennial allergic rhinitis and 112.9 +/ 25.6 ng/ml for patients with both perennial and seasonal allergy. Patients with nasal polyps had mean nasal ECP levels of 146.9 +/- 57.7 ng/ml in absence of allergy and 147.9 +/- 54.9 ng/ml in the presence of allergy. Nasal ECP was 67.0 +/- 22.4 for patients with hyperreactive rhinitis. We found a significant correlation of 0.95 between nasal eosinophils and nasal ECP. Nasal ECP and a subjective symptom score only correlate significantly for chronic sinusitis. We conclude that monitoring native nasal fluid ECP levels may be useful in the diagnosis and management of nasal inflammation. Elevated ECP in nasal secretion may originate from upregulated eosinophil degranulation and thus is a marker for local inflammation although not specific for any particular nasal disease. PMID- 7889430 TI - The importance of eosinophil activation for the development of allergen-induced bronchial hyperreactivity in conscious, unrestrained guinea-pigs. AB - Using a newly developed guinea-pig model of asthma, characterized by allergen induced early and late phase asthmatic reactions, bronchial hyperreactivity (BHR) and airway inflammation, the importance of eosinophil activation for the development of BHR to inhaled histamine was investigated at 6 h (after the early reaction) and 24 h (after the late reaction) after allergen provocation. Eosinophil activation was assessed by a sensitive kinetic assay for eosinophil peroxidase (EPO) activity, suitable for bronchoalveolar lavage (BAL) analysis. A significant 2.9-fold (P < 0.01) increase in bronchial reactivity to histamine was observed at 6 h after allergen exposure, which was associated with a 2.9-fold increase in the number of eosinophils (P < 0.05) and a 6.7-fold increase in EPO activity (P < 0.01) in the BAL fluid. At 24 h after allergen exposure the bronchial reactivity to histamine was lower (1.7-fold), but still significantly enhanced (P < 0.01). By contrast, the number of eosinophils was further increased compared with 6 h after provocation (3.8-fold, P < 0.05), while the EPO activity remained stable at 6 h levels. The number of eosinophils was significantly correlated with EPO activity at 6 h (r = 0.62; P < 0.05), but not at 24 h after provocation. No significant correlation was observed between the number of eosinophils in the BAL fluid and BHR to histamine at either time point.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889431 TI - House dust mite and cat allergen in different indoor environments. AB - Allergy to house dust mites (HDM) and domestic pets is a major cause of asthma. People in developed countries spend more than 90% of their time indoors. We have measured levels of HDM allergen Der pI and cat allergen Fel dI in public buildings and public transport. Dust samples were collected by vacuuming a 1 m2 area for 2 min from five schools, six hotels, four cinemas, six pubs, three buses, two trains and 12 domestic households without a cat. Der pI and Fel dI were assayed with monoclonal antibodies in a two-site immunometric ELISA. Der pI concentration was significantly higher in the private homes than in comparable sites in public places except for cinema seats (where high values were found) compared with domestic sofas. Der pI > 2000 ng/g of fine dust was found in 30% of the upholstered seats, 9% having a concentration > 10,000 ng/g. Fel dI levels were significantly higher in the dust from upholstered seats (geometric mean 14.88 micrograms/g) than in carpeted floors (geometric mean 0.73 micrograms/g), and in public places than in private homes. Fel dI > 8 micrograms/g was found in 79% of the upholstered seats or furniture sampled in public buildings or public transport. In conclusion, upholstered seats from public buildings and public transport constitute an allergen reservoir for continuous contamination of the indoor environment which could compromise the effects of allergen avoidance employed at home. PMID- 7889432 TI - Effects of castration and testosterone on Fel dI production by sebaceous glands of male cats: I--Immunological assessment. AB - Fel dI is produced by salivary and sebaceous glands. Hormonal control of sebum production is clearly established. The influence of cat castration and supplementary treatment with testosterone on the production of sebum and Fel dI in cat skin have been researched in this study. On day 1, 12 male cats were anaesthetized and three skin areas carefully shaven. Then the level of lipids on skin surface was measured by means of a photometric method. Finally, the three areas of skin were washed with 5ml of distilled water through a plastic cylinder. Fel dI collected in the washes was measured with a two-site monoclonal antibody based ELISA. On day 2, six cats were castrated, the other six were used as a control group. Two and 4 weeks later, the levels of lipids and Fel dI in skin washes were measured again in all cats. On day 30, the six castrated cats were injected intramuscularly with prolonged-action testosterone. Two weeks later, quantification of lipids and Fel dI in all animals was repeated. Sebum and Fel dI levels decreased in all castrated animals. Injecting the castrated cats with testosterone led to a significant increase in sebum and Fel dI production. Our findings indicate that Fel dI production is influenced by the production of hormones. PMID- 7889434 TI - Fungal growth on wine corks--a potential source of exposure to susceptible individuals. PMID- 7889433 TI - Effects of castration and testosterone on Fel dI production by sebaceous glands of male cats: II--Morphometric assessment. AB - A morphometric study of cat sebaceous glands was performed to evaluate the effects of castration and testosterone treatments. Skin biopsies were taken in six cats before castration, after castration and after the testosterone injections administered after castration (total number of biopsies: 18). Ninety 8 microns thick sections of each biopsy were assessed for image analysis processing (SAMBA 2005, ALCATEL TITN). The variations in glands and cells size were evaluated on digitized microscopic images by morphometric parameters included in the SAMBA software package. An original software was developed for the analysis of the spacial gland structure. The best morphometric parameters were selected in a first step of the study, and included the nuclear surface (NS), the cell surface (CS) and the nuclear/cellular surface ratio (N/C). These three parameters were then compared in each group of samples for the six cats. It was shown that after castration the N/C (21%) significantly increased compared with prior to castration (12.6%). This 59.8% increase was mainly due to cell cytoplasm shrinking reflecting a decrease of the cell activity. The testosterone administered after castration produced a reverse effect with a N/C ratio back to normal (11.4%) and a significant cell cytoplasm and gland enlargement as shown by the three dimension constructions. This morphometric data correlated with the measurement of sebum and Fel dI productions. The negative effects of castration and the positive effects of testosterone on the sebaceous cells and glands volume favour the hypothesis that cat sebaceous cells are subject to hormonal control this is also likely to apply to the Fel dI production. PMID- 7889435 TI - Cholesterol hypothesis vindicated by simvastatin study. Why did it take so long? PMID- 7889436 TI - Benefits of beta-blocker prophylaxis against supraventricular arrhythmias following aortocoronary bypass surgery in routine clinical practice. AB - OBJECTIVE: To determine the effectiveness of beta-blocker therapy for suppression of supraventricular arrhythmias (SVA) following aortocoronary bypass surgery (ACBS) in routine clinical practice. DESIGN: Prospective data collection and retrospective assessment of the occurrence of SVA following ACBS. SETTING: Cardiovascular surgery intensive care unit and hospital patient ward with electrocardiogram (ECG) monitoring facilities. PATIENTS: Ninety-two consecutive patients without contraindication to beta-blockade admitted for elective ACBS. INTERVENTIONS: Patients having persistent SVA requiring drug therapy during a minimum of four days of ECG monitoring were identified, and the use of beta blocker therapy following ACBS was noted. MAIN RESULTS: Persistent SVA developed in 24 of 92 patients. Beta-blockers were taken by 11 of 24 patients with SVA compared with 49 of 68 without SVA (P = 0.02). Characteristics were similar for SVA and non-SVA patients including sex, left ventricular function, number of bypass grafts, preoperation beta-blocker use and postoperation intravenous esmolol therapy. SVA occurred 48 +/- 6 h (mean +/- SD) post-ACBS lasting 47 +/- 11 h. Patients with SVA were older than those without (64 +/- 2 versus 57 +/- 1 years, P = 0.002). Hospital stay after ACBS was increased (P < 0.001) in SVA versus non-SVA patients (8.7 +/- 0.7 versus 6.5 +/- 0.1 days). CONCLUSIONS: Oral beta-blocker prophylaxis is effective in preventing SVA after ACBS when used routinely in unselected patients. Failure to develop standardized approaches to beta-blocker therapy following ACBS may result in prolonged hospitalization. PMID- 7889437 TI - Effects of routine premedication for cardiac catheterization on sedation, level of anxiety and arterial oxygen saturation. AB - OBJECTIVE: To assess the efficacy and side effects of routine premedication in patients undergoing cardiac catheterization procedures in a tertiary cardiac care institute. The criteria used included: arterial hemoglobin oxygen saturation (%SaO2), level of sedation and level of anxiety before and after the procedure. Overall patient satisfaction was also quantified. DESIGN: Sixty-two adult patients scheduled for cardiac catheterization procedures were recruited for the study. They were premedicated with one of several premedication regimens: oral diazepam 5 to 10 mg; oral lorazepam 1 mg; oral diazepam 10 mg+oral promethazine 25 mg; or oral diazepam 10 mg+oral diphenhydramine 25 mg. No attempt was made to control the premedication the patients received; it was ordered by each patient's cardiologist according to personal preference. Patients underwent pulse oximetry and evaluation of sedation, anxiety and level of satisfaction before and after cardiac catheterization. RESULTS: All patients tested had values for mean precatheterization %SaO2 above 92%. No patient had postcatheterization %SaO2 readings below that defined as indicating clinically significant hypoxemia (%SaO2 less than 90%). Patients were awake or lightly sedated before and after cardiac catheterization. Thirteen per cent of patients suffered from high levels of anxiety before, and 16% during, cardiac catheterization. Twenty-three per cent of patients reported being dissatisfied with the premedication before, and 10% of patients reported being dissatisfied during, cardiac catheterization. CONCLUSIONS: Clinically significant hypoxemia and oversedation are not problems for most patients given the types and doses of precatheterization medication used in the study population. The premedication schedules followed in the study failed to provide satisfaction and anxiolysis in a significant number of those studied. PMID- 7889438 TI - Lipoprotein(a) and apolipoproteins B and A-I after acute myocardial infarction. AB - OBJECTIVE: To assess the temporal behaviour of plasma lipoprotein(a) [Lp(a)]--a low density lipoprotein-like particle whose plasma levels are associated with atherosclerosis risk--and apolipoproteins (apo) B and A-I (the major protein components of low and high density lipoproteins, respectively) in acute myocardial infarction (AMI), and to determined the effect of tissue plasminogen activator (tPA) on them. DESIGN AND PATIENTS: Serial Lp(a), apoB and apoA-I determinations were obtained over eight days in 19 AMI patients who were part of a randomized, placebo (n = 7) controlled trial of tPA (n = 12). MAIN RESULTS: At 48 h postinfarct, plasma Lp(a) and apoB concentrations were, respectively, 20% (24.9 +/- 3.0 to 19.9 +/- 2.9 mg/dL, P < 0.05) and 28% (1.37 +/- 0.10 to 0.99 +/- 0.11 mM/L, P < 0.05) below baseline values. ApoA-I concentrations were unchanged at 48 h postinfarct. At 192 h postinfarct, Lp(a) rebounded to 36% above baseline (24.9 +/- 3.0 to 33.9 +/- 3.9 mg/dL, P < 0.05), apoB returned to baseline (1.37 +/- 0.10 versus 1.33 +/- 0.11 g/L, P < 0.05) and apoA-I was 15% below baseline (1.43 +/- 0.06 to 1.21 +/- 0.06 g/L, not significant). Administration of tPA had no effect on any of these changes. CONCLUSIONS: Plasma Lp(a) and apolipoproteins undergo shifts from baseline values in the postinfarct period and tPA has no effect on these variations. PMID- 7889439 TI - Aortocoronary vein graft spasm during angiography. AB - OBJECTIVE: To determine the frequency and clinical significance of aorto-coronary vein graft spasm during angiography. DESIGN: Retrospective review of angiograms and subsequent correlation with clinical outcome. PATIENTS: A total of 1264 patients having bypass surgery between 1971 and 1986. MAIN RESULTS: Twenty-four men, aged 31 to 54 years, demonstrated spasm in 31 vein grafts at angiography. Vein graft spasm occurred in 13 anterior descending, 12 right coronary, four marginocircumflex and two diagonal grafts. Spasm occurred less than six months after surgery in six cases, six to 12 months after surgery in 18 cases and five or more years after surgery in two cases. There was technical difficulty associated with the intubation of 15 of the 31 grafts. In all but two of the cases, the graft spasm was proximal. There was ischemic discomfort and/or electrocardiographic changes in nine patients, with ventricular fibrillation in three cases. Three cases of very severe vein graft spasm could be reversed with vasodilators, but in three others it could not be relieved and the grafts occluded irreversibly, leading to myocardial infarction in two patients. CONCLUSION: Aortocoronary vein graft spasm may occur during angiography and may be associated with more technically difficult graft intubation. Severe vein graft spasm may respond to vasodilators but can progress to graft occlusion with myocardial infarction. Aortocoronary vein graft spasm during angiography is not related to any higher incidence of spontaneous graft closure or recurrent angina. PMID- 7889441 TI - The enigma of sudden cardiac death related to dieting. AB - The use of liquid protein products for treatment of obesity in the United States in the 1960s and '70s was associated with an increased risk of sudden cardiac death. The latter was related to long QT interval occurring in the absence of structural abnormalities of the heart. In an attempt to increase understanding of this phenomenon, the authors examined the possible role of diet-related circumstances. No evidence of increased incidence of sudden cardiac death or significant lengthening of QT interval in obesity, weight loss, starvation and dieting by methods other than liquid protein intake were found. It was concluded that sudden cardiac death during use of liquid protein products remains an enigma, but that other methods of properly medically supervised dieting appear to be safe. PMID- 7889440 TI - Individual variation in the effects of ASA on platelet function: implications for the use of ASA clinically. AB - OBJECTIVE: To determine whether acetylsalicylic acid (ASA) inhibits hemostasis and platelet function in some individuals (ASA responders) but not in others (ASA nonresponders). DESIGN: In this two-part study, part 1 was a randomized, double blind crossover study of the effects of various single doses of ASA (80 to 1300 mg) on primary hemostasis and platelet function. Part 2 was a prospective cohort study of the effects of a chronic dose of ASA (325 mg) on primary hemostasis and platelet function. SETTING: A hospital research laboratory and a cardiac care ward. SUBJECTS: Part 1: 10 healthy volunteers (five male, five female). Part 2: 40 consecutive patients undergoing elective coronary artery bypass grafting (CABG). RESULTS: Part 1: ASA, in a dose-related manner, prolonged the bleeding time in 60% of volunteers (ASA responders), which was associated with decreases in platelet thromboxane (Tx) A2 and 12-hydroxyeicosatetraenoic acid (12-HETE) synthesis and in platelet aggregation and adhesion. However, in volunteers whose bleeding time was not prolonged (ASA nonresponders), platelet 12-HETE synthesis and platelet adhesion were unchanged or increased (P < 0.001), despite platelet TxA2 and platelet aggregation being inhibited. Part 2: similarly, 58% of the CABG patients were ASA responders and all of their platelet biochemistry and function tests were inhibited, while in the CABG patient ASA nonresponders (no prolongation of bleeding time), platelet 12-HETE and platelet adhesion were increased (P < 0.001). PMID- 7889442 TI - Benign pneumopericardium and tamponade. AB - A 49-year-old obese female was admitted for acute onset pleuritic chest pain. Previous history was significant for surgical correction of a lower esophageal ring. Echocardiography revealed a pericardial effusion, which resolved with steroids. One week later, the patient complained of similar symptoms. Physical examination was consistent with tamponade, while a Hammond crunch was noted over the sternum. Chest x-ray revealed a pneumopericardium. Operative findings consisted of an intrathoracic stomach, a greater curvature ulcer that had perforated the pericardium and a mediastinal abscess. A pericardial window was created, a drain was placed and the perforated ulcer was repaired. Postoperative course was complicated by fever and gastrointestinal bleeding. The patient died suddenly on the 30th postoperative day. Autopsy revealed a massive pulmonary embolus, bleeding esophageal ulcer, healed gastric ulcer and serofibrinous pericarditis. This case illustrates that, while the immediate treatment of tension pyopneumopericardium is usually successful, postoperative mortality remains elevated. PMID- 7889443 TI - Aortic ring abscess and mitral valve aneurysm in aortic valvular endocarditis: enhanced diagnosis with transesophageal echocardiography. AB - Aortic ring abscess and mitral valve aneurysms complicating infective endocarditis have previously been described as surgical or autopsy findings. More recently, transesophageal echocardiography has been shown to be more sensitive than standard transthoracic echocardiography or other imaging modalities in detecting each of these complications. Since aortic ring abscess and mitral valve aneurysms virtually mandate surgical intervention, their early detection may be crucial. This report describes a 35-year-old male with congenitally abnormal aortic valve which became infected and in whom both an aortic ring abscess and mitral valve aneurysm occurred. These findings are discussed and the pertinent literature is reviewed. PMID- 7889444 TI - Comparative pharmacology of calcium antagonists. AB - OBJECTIVE: To compare clinically relevant pharmacokinetic, pharmacodynamic and toxico logical characteristics of calcium-modulating compounds used in ischemic heart disease. DATA SOURCES: A MEDLINE search (1990 pt B to 1991 pt A revised for 1993; 1991 pt B to 1992 revised for 1993; and January to May 1993) combining the search phrases 'calcium channel blockers', 'myocardial ischemia', 'pharmacodynamics' and 'pharmacokinetics', and a search in Compact Cambridge Drug Information Source vol-6 (revised 1992, fourth quarter) using the search phrase 'calcium antagonists' and medical subject headings (MeSH) 'pharmacokinetics' and 'pharmacodynamics' were used to obtain title and abstract information on available current literature. STUDY SELECTION: Review articles, proceedings and studies published in English and available within the University of Saskatchewan library system, as they appeared to relate closely to the objective, were obtained for closer evaluation. In addition, primary references were examined, and journal reprints were selected from the authors' files. DATA EXTRACTION: The focus was on studies and objective reviews that profiled one or more representative compounds in a manner suitable for deriving background and comparative information pertaining to the objective. Data from multiple studies, or from studies that employed multiple methodological approaches, were preferentially extracted and summarized for presentation. DATA SYNTHESIS: The role of calcium in cardiac and vascular smooth muscle physiology was reviewed, highlighting the major mechanisms responsible for maintaining calcium homeostasis in these cells. With a focus on verapamil, diltiazem and 1,4-dihydropyridines currently employed in the treatment of cardiovascular disorders, a general survey of their sites of action, tissue selective pharmacodynamics, pharmacokinetic properties and side effects was undertaken in a comparative context. CONCLUSIONS: Calcium antagonists are employed in the treatment of angina, certain cardiac arrhythmias and hypertension. They are a chemically and pharmacologically heterogeneous group of compounds that act principally to inhibit the influx of calcium across certain voltage-dependent membrane channels. Concepts pertaining to calcium mobilization in the pathophysiology of myocardial ischemia, particularly at the molecular level, have evolved remarkably over the past decade. The repertoire of agents having calcium-regulating properties has expanded in parallel. The task of integrating new knowledge in both of these areas requires further attention in order to determine optimal approaches to treatment. PMID- 7889445 TI - Cardiovascular Technology Symposium. Ottawa, May 12-14, 1994. Abstracts. PMID- 7889446 TI - The Uncertainty Stress Scale: its development and psychometric properties. AB - This paper describes the development and testing of a new scale--The Uncertainty Stress Scale--which measures uncertainty in illness-related situations, and the stress, threat, and positive feelings generated from the uncertain state. The theoretical and empirical basis of the scale is presented. Evidence which supports the scale's reliability and its content, concurrent, and construct validity is presented from several studies of people experiencing acute and chronic medical conditions. Descriptions and rationales for revisions are described. PMID- 7889447 TI - Hope and social support as coping resources for adults waiting for cardiac transplantation. AB - Previous research has indicated that interpersonal support and hopefulness are important for people waiting for cardiac transplantation. However, little is known about their supportive networks, or whether support and hope are factors that enable coping during the waiting period. This study described the social networks of cardiac transplant candidates, and explored whether social support and hope contributed to effective coping. Thirty-one individuals in four Canadian transplant centres completed questionnaires regarding social support (Norbeck Social Support Questionnaire), hope (Miller Hope Scale), and coping (Jalowiec Coping Scale). Telephone interviews provided supplementary data about perceptions of helpful support behaviours. Study findings suggest that hope was the only variable that contributed to coping effectiveness (R2 = .41) and that respondents' social networks (primarily family, friends, and health professionals) were important sources of support. The data provide insight into the behaviours that transplant candidates find supportive and suggest strategies to maintain hopefulness during the waiting period. PMID- 7889448 TI - Self-efficacy, perfectionism, and stress in Canadian nurses. AB - The current study examined the relationship between stress in nurses and their reported levels of job and life satisfaction, while also assessing the construct validity of theories of perfectionism and self-efficacy as these apply to the profession of nursing. One hundred and ninety-six nurses employed in Toronto and Windsor, Ontario completed measures of stress, perfectionism, self-efficacy, and job and life satisfaction as dependent variables. Generally, nurses who reported high levels of socially-prescribed and other-oriented perfectionism, and low levels of self-efficacy, also reported low levels of job satisfaction. Significant negative correlations were obtained between the number of reported nursing stressors and job satisfaction. The data also indicated that higher levels of socially-prescribed perfectionism and higher levels of self-efficacy were strongly related to both job and life stress. Some comments, interpretation, and implications of findings are presented. PMID- 7889449 TI - Relationships between stress, coping resources, and satisfaction with family functioning in families of children with disabilities. AB - The purpose of the current descriptive correlational study was to examine relations between stress, coping resources, and satisfaction with family functioning in families caring for children with developmental disabilities at home. Fifty families who used the services of a respite care program were surveyed to examine relationships among child characteristics (behavioral problems and handicapping conditions); coping resources including mastery and health, esteem and communication, family hardiness, and social support; and the primary outcome variable of satisfaction with family functioning. Families of children with developmental disabilities experience significant stressors in terms of the severity of their child's handicapping conditions and behaviour problems. However, they reported satisfactory coping resources such as mastery and health, hardiness, and esteem and communication. Although they were lower than normative scores, social support scores for spouses and friends were related to satisfaction with family functioning. Implications for practitioners are discussed. PMID- 7889450 TI - [A method for validating a translated questionnaire]. AB - This paper describes Haccoun's (1987) technique for validating a translated questionnaire. This method is based on the idea that if a questionnaire is well translated, bilingual subjects will provide equivalent responses to questions in either language. A single group of bilingual subjects is given both language versions of the questionnaires at two different times in random order. Subsequently: 1) test-retest reliability coefficients are computed for the original and translated versions; 2) correlation coefficients between the original and translated versions of the instrument are computed and compared (simultaneous correlations between languages); 3) the correlations between the original version at time 1 and the translated version at time 2 and vice versa are computed and compared (cross-correlations); and 4) the cross-correlations are compared to the test-retest reliabilities within each language. The final step indicates whether the translated version of the instrument is equivalent to the original. The authors use Haccoun's technique to demonstrate that a French translated version of Alcock et al.'s (1990) questionnaire on nurses' perceptions of nursing research is reliable and statistically equivalent to the original. PMID- 7889451 TI - Methodological challenges in coping and adaptation research. PMID- 7889452 TI - A system-linked research unit on "health and social service utilization". PMID- 7889453 TI - In vitro viability of cryopreserved equine embryos following different freezing protocols. AB - The main objective of this study was to evaluate two freezing protocols and the effect of agar embedding on survival of day 6.5 equine embryos. A total of 133 embryos were used, in one group (n = 51), embryos were first embedded in agar before the freezing protocol was started. A freezing protocol to -30 degrees C or -33 degrees C was used before plunging embryos into liquid nitrogen (LN2). The embryos were thawed in water at 37 degrees C, evaluated and placed in culture. After 24 h culture, the embryos were evaluated for their morphology and development. No differences were observed between embryos plunged at -30 degrees or at -33 degrees C in LN2. The analysis of the morphology and development after thawing showed that the diameter and developmental stage at freezing correlated with embryo survival. Morula and early blastocyst stages of development were associated with better quality after freezing and thawing and had a better potential to survive after in vitro culture (p < 0.05) compared to more advanced stages. The agar failed to protect embryos from zona pellucida damage, but a tendency to prevent rupture was observed in larger embedded embryos. PMID- 7889454 TI - Coagulation factor XI deficiency in Holstein cattle: expression and distribution of factor XI activity. AB - Factor XI (F XI) is a plasma protein that participates in the blood coagulation process. A study of the expression of F XI activity in Holstein cattle has confirmed that the inheritance of F XI deficiency is autosomal with severe deficiency in homozygotes (mean F XI level 2%, SD 1%), and partial deficiency in heterozygotes (mean F XI level 38%, SD 10%; normal mean F XI level 94%, SD 21%). In a total of 1469 males evaluated for F XI levels, 47 or 3.1% were identified as heterozygous and only one as homozygous for the disorder. In part because of the lack of a discrete distinction in the expression of F XI between heterozygous and normal animals, not all of the animals tested could be uniquely classified on the basis of the plasma F XI values. A mean F XI value of 53% (SD 7%) was found in a group of animals that were categorized as low normal/high heterozygous. If this group of cattle had been classified on the basis of the criterion used to classify human beings then these animals would have been categorized as heterozygous since the mean F XI value for proven bovine heterozygotes is approximately 20% lower than the values found in the human counterpart. Like the human form of the disease, however, there appears to be a low frequency of hemorrhagic episodes associated with F XI deficiency in cattle. PMID- 7889455 TI - The cardiovascular sparing effect of fentanyl and atropine, administered to enflurane anesthetized dogs. AB - Cardiovascular effects of high dose opioid together with low dose inhalant were compared with inhalant alone to determine whether opioid/inhalant techniques were less depressant on the cardiovascular system. The effects of positive pressure ventilation and increasing heart rate to a more physiological level were also studied. Cardiovascular measurements recorded during administration of enflurane at 1.3 minimum alveolar concentration (MAC; 2.89 +/- 0.02%) to spontaneously breathing dogs (time 1) and during controlled ventilation [arterial carbon dioxide tension at 40 +/- 3 mmHg (time 2)] were similar. At time 2, mixed venous oxygen tension and arterial and mixed venous carbon dioxide tensions were significantly decreased, while arterial and mixed venous pH were significantly increased compared to measurements at time 1. After administration of fentanyl to achieve plasma fentanyl concentration of 71.7 +/- 14.4 ng/mL and reduction of enflurane concentration to yield 1.3 MAC multiple (0.99 +/- 0.01%), heart rate significantly decreased, while mean arterial pressure, central venous pressure, stroke index, and systemic vascular resistance index increased compared to measurements taken at times 1 and 2. Pulmonary arterial occlusion pressure was significantly increased compared to measurements taken at time 2. After administration of atropine until heart rate was 93 +/- 5 beats/min (plasma fentanyl concentration 64.5 +/- 13.5 ng/mL) heart rate, mean arterial pressure, cardiac index, oxygen delivery index, and venous admixture increased significantly compared to values obtained at all other times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889456 TI - The parasympatholytic effects of atropine sulfate and glycopyrrolate in rats and rabbits. AB - Nine groups of rats (n = 5 per group) received an intramuscular (IM) injection of one of the following drugs or drug combinations: saline, atropine (0.05 mg/kg), glycopyrrolate (0.5 mg/kg), ketamine:xylazine (85:15 mg/kg), ketamine:detomidine (60:10 mg/kg), atropine:ketamine:xylazine (0.05: 85:15 mg/kg), glycopyrrolate: ketamine:xylazine (0.5:85:15 mg/kg), atropine:ketamine:detomidine (0.05: 60:10 mg/kg) or glycopyrrolate: ketamine:detomidine (0.5:60:10). Similarly six groups of rabbits (n = 5) received an IM injection of either saline, atropine (0.2 mg/kg), atropine (2 mg/kg), glycopyrrolate (0.1 mg/kg), ketamine:xylazine (35:10 mg/kg) or glycopyrrolate:ketamine:xylazine (0.1:35:10 mg/kg). In rats, atropine sulfate (0.05 mg/kg) and glycopyrrolate (0.5 mg/kg) produced an increase in heart rate for 30 and 240 min, respectively. In rabbits atropine sulfate at either 0.2 or 2.0 mg/kg did not induce a significant increase in heart rate, but glycopyrrolate (0.1 mg/kg) elevated the heart rate above saline treated animals for over 50 min. Both atropine and glycopyrrolate provided protection against a decrease in heart rate in rats anesthetized with ketamine: xylazine (85:15 mg/kg) or ketamine: detomidine (60:10 mg/kg); however, glycopyrrolate was significantly more effective in maintaining the heart rate within the normal range. Glycopprrolate also prevented a decrease in heart rate in rabbits anesthetized with ketamine:xylazine (35:5 mg/kg). Neither glycopyrrolate nor atropine influenced respiration rate, core body temperature or systolic blood pressure when used alone or when combined with the injectable anesthetic. Glycopyrrolate is an effective anticholinergic agent in rabbits and rodents and more useful as a preanesthetic agent than atropine sulfate in these animals. PMID- 7889458 TI - Serodiagnosis of Salmonella dublin infection in Danish dairy herds using O antigen based enzyme-linked immunosorbent assay. AB - Usefulness of two enzyme-linked immunosorbent assays (ELISA) for screening of dairy herds for antibodies to lipopolysaccharide (LPS) of Salmonella dublin (O:1,9,12) was investigated. Sera (3097) were collected from 40 dairy herds located in three areas of Denmark with different prevalence of salmonellosis: ten salmonellosis-free herds from the island of Samso where there is no history of salmonellosis, ten salmonellosis-free herds from the island of Sealand where outbreaks are infrequent, and 20 salmonella infected herds from Jutland where salmonellosis is enzootic. The samples were analyzed for antibodies to S. dublin LPS using an indirect (O:9,12) and a blocking (O:9) ELISA. Using herd history of salmonellosis, herd location and clinical state of the herds as reference, the herd sensitivity and herd specificity of the tests were 100% and 100% in the indirect ELISA and 95% and 100% in the blocking ELISA, respectively. A significant correlation was found between the two tests (rs = 0.46, p < 0.001). However, the indirect ELISA detected more seropositive animals than the blocking ELISA (17% vs. 7%, respectively). In calves from Sealand, level of background reaction was significantly lower (p < 0.001) compared to the heifers and the cows. The percentages of seropositive calves in both tests were higher (p < 0.01) in comparison to cows (19 vs. 8 in indirect ELISA, and 14 vs. 6 in blocking ELISA, respectively). Results of the study indicated that it is possible to apply LPS ELISA in serological screening for salmonellosis. PMID- 7889457 TI - A national survey to estimate the prevalence of Salmonella species among Canadian registered commercial turkey flocks. AB - In 1990-1991, a national survey was conducted to estimate the prevalence of Salmonella species among Canadian commercial turkey flocks. Two hundred and seventy flocks were randomly selected across Canada. The proportion sampled from each province was selected according to each province's share of the national turkey market. Samples, consisting of 12 pooled litter and four pooled dust samples, were used to determine the Salmonella status of the environment of each flock. Additionally, a one kilogram sample of feed was taken from each flock premise. Salmonella was recovered from environmental samples in 234/270 (86.7%) of flocks and from feed samples in 26/266 (9.8%) of flocks. Forty-eight different Salmonella serovars were isolated from flock environmental samples. The most prevalent serovars were S. anatum, S. hadar, S. agona, S. heidelberg and S. saintpaul which were isolated from 53/270 (19.6%), 49/270 (18.1%), 49/270 (18.1%), 42/270 (15.6%) and 34/270 (12.6%) flocks, respectively. PMID- 7889459 TI - Activation of murine macrophages and lymphocytes by Ureaplasma diversum. AB - Ureaplasma diversum is a pathogen in the bovine reproductive tract. The objective of the research was to study interactions with macrophages and lymphocytes which might elucidate aspects of pathogenetic mechanisms of this organism. We studied the activation of murine macrophages of C3H/HeN (LPS-responder) and C3H/HeJ (LPS low-responder) genotype for TNF-alpha, IL-6, IL-1 and nitric oxide production and blastogenic response of C3H/HeJ splenocytes after Ureaplasma diversum stimulation. Live and heat-killed U. diversum induced TNF-alpha, IL-6 and IL-1 in peritoneal macrophage cultures of both C3H/HeN and C3H/HeJ mice in a dose dependent manner. Interferon-gamma modulated the cytokine production, by increasing the production of TNF-alpha, IL-6 and nitric oxide, but IL-1 secretion was only enhanced in C3H/HeJ macrophages stimulated by live ureaplasmas. Supernatant of U. diversum sonicate was mitogenic for murine spleen lymphocytes. The blastogenic response was dose dependent, and stimulation with both U. diversum and Concanavalin A seemed to have an additive effect. These results suggest that U. diversum, similar to other mycoplasmas, activates murine macrophages and lymphoid cells. The studies should be repeated with bovine cells in order to elucidate pathogenetic aspects of inflammation in cattle caused by U. diversum. PMID- 7889460 TI - Morphometric analysis of enteric lesions in C3H/HeN mice inoculated with Serpulina hyodysenteriae serotypes 2 and 4 with or without oral streptomycin pretreatment. AB - The segmental distribution and sequential progression and the role of the indigenous bacterial flora in the development of enteric lesions associated with Serpulina hyodysenteriae infection in laboratory mice have not been defined. We examined the distribution and sequential morphometric changes in the large intestine of mice orally inoculated with S. hyodysenteriae serotypes 2 and 4. To determine the role of colonization resistance conferred by the indigenous bacterial flora, 40 female C3H/HeN mice were administered water alone or water containing 5 mg/mL streptomycin sulfate ad libitum for seven days prior to orogastric inoculation either with S. hyodysenteriae or sterile trypticase soy broth (TSB). Clinical signs were monitored daily and three mice per group were necropsied on postinoculation days (PID) 7 and 14 for pathological assessment of the cecum, proximal colon, transverse colon, and descending colon, and bacteriological culture of the cecum for S. hyodysenteriae. Weekly pooled fecal samples were collected from each group for determination of total numbers of anaerobe bacteria. Gross examination revealed soft fecal pellets on PID 7 and 14 and catarrhal typhlitis on PID 14, irrespective of streptomycin pretreatment. The recovery rates of S. hyodysenteriae from the ceca of serotype 2- and serotype 4 inoculated mice was 100 and 91.7%, respectively. Statistically significant differences in morphometric changes between TSB- and S. hyodysenteriae-inoculated mice were present on PID 7 and 14 and were restricted to the cecum. Although oral administration of streptomycin for seven days prior to S. hyodysenteriae inoculation resulted in a significant reduction in the numbers of fecal anaerobes, it did not affect the colonization, distribution, severity, or progression of cecal lesions. PMID- 7889461 TI - Antigenic characterization of an H3N2 swine influenza virus isolated from pigs with proliferative and necrotizing pneumonia in Quebec. AB - A new strain of swine influenza A virus, designated A/Swine/Saint Hyacinthe/150/90 has been isolated from pigs with severe proliferative and necrotizing pneumonia in Quebec. The antigenic characterization of the hemagglutinin was performed by hemagglutination inhibition test, immunoblot and indirect immunoprecipitation using polyclonal antisera. Only the last test was able to detect an antigenic relationship between the hemagglutinin of this isolate and an H3 subtype influenza virus. The immunoprecipitation test was a useful alternative for determining the hemagglutinin of influenza A virus subtypes. The neuraminidase inhibition test demonstrated a reactivity between the A/Swine/Saint-Hyacinthe/150/90 and antiserum against a N2 subtype influenza virus. Our results indicate that this new strain isolated for the first time in the porcine population of Canada is related to A/Sw/Hong Kong/76 H3N2 swine influenza virus. PMID- 7889462 TI - Persistence of porcine reproductive and respiratory syndrome virus infection in a swine operation. AB - A herd of Quebec seedstock pigs experienced in early 1992 a typical outbreak of porcine reproductive and respiratory syndrome (PRRS) associated with lesions of interstitial, proliferative and necrotizing pneumonia in weaned piglets. The nature of the infection was confirmed by serology using indirect immunofluorescence (IIF) and virus isolation in primary cultures of porcine alveolar macrophages (PAM). Farm production recovered after eight weeks of losses. In order to evaluate the persistence of infection in the herd, five SPF piglets were introduced in two different sections of the PRRS-affected barn four months after the disappearance of clinical symptoms, and two others were placed in a neighboring building with apparently healthy farrow-to-finnish pigs. Clinical signs, body temperature, humoral immune response, virological and histopathological findings were recorded over a 42-day period. Clinical signs were evident in all of the sentinels and prolonged fever (> or = 40 degrees C) was recorded one day post-exposure (PE). Antibody titers to PRRS virus could be detected by IIF on PAM seven days PE, and reached 1:1024 by day 21 PE. Three of the sentinels developed significant virus neutralizing antibody titers (> 1:8 to < or = 1:128) by day 35 PE. In all cases, the virus could be isolated from the serum between day 7 and 42 PE. Thus, the virus and specific antibodies coexisted for several weeks. Lesions of interstitial pneumonia was demonstrated in few animals. In experimental inoculation studies, the viral strain isolated from the sentinel pigs produced severe reproductive disorders in two sows inoculated at 95 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889463 TI - Immunization of mice against Streptococcus suis serotype 2 infections using a live avirulent strain. AB - In this study, the IgG response of mice injected with two virulent strains and one avirulent Streptococcus suis capsular type 2 strain was compared by Western blotting. The serum from mice immunized against the avirulent strain could recognize most proteins of the various strains tested and similar results were obtained with serum from mice injected with virulent strains. The live avirulent strain was injected twice (days 0 and 10) to groups of five mice, and four virulent strains from different geographical origins were used to challenge the animals. All mice, except one in one group, survived the challenge. These results suggest that a live avirulent strain could be used for immunization of swine, the natural host. PMID- 7889465 TI - [Direct approach for demonstrating free radical phenomena during equine postanesthetic myopathy: preliminary study]. AB - This preliminary study demonstrated the existence of a free radical generation during an experimental postischemic muscular reperfusion in a halothane anesthetized horse. The authors used alpha-phenyl-N-tert-butylnitrone as a spin trap agent and the electronic paramagnetic resonance method to observe in vivo a free radical generation. PMID- 7889464 TI - Vaccination of chickens with a recombinant fowlpox virus containing the hemagglutinin-neuraminidase gene of Newcastle disease virus under the control of the fowlpox virus thymidine kinase promoter. AB - When chickens were vaccinated with a recombinant fowlpox virus (FPV) containing the Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) cDNA under the control of the thymidine kinase (TK) promoter and inserted into the FPV TK gene, the FPV antibody response to the recombinant virus was similar to the response to vaccination with standard FPV, and the recombinant virus protected chickens against challenge with virulent FPV. While the presence of the NDV HN cDNA was demonstrated in the recombinant virus, which was stable on serial passage, expression of HN was not detected by hemagglutination, Western blot analysis or immunoprecipitation of infected cell lysate. Chickens vaccinated with the recombinant virus failed to mount an NDV hemagglutination-inhibition antibody response, and they did not resist challenge with velogenic NDV. It was concluded that the TK promoter was too weak to drive the HN gene, but that the insertion into the FPV TK gene did not reduce the immunogenicity of the virus. PMID- 7889466 TI - 6th Annual meeting of the Japanese Research Society for Gastroenterological Carcinogenesis. Proceedings. Kobe, Japan, September 1994. PMID- 7889467 TI - Genetic alterations in human gastrointestinal cancers. The application to molecular diagnosis. AB - Gastrointestinal cancers involve genetic alterations in multiple oncogenes, multiple tumor suppressor genes, and multiple DNA repair genes. However, common and different genetic changes are observed in esophageal, gastric, and colorectal carcinomas, respectively. Inactivation of the p53 gene and expression of CD44 abnormal transcripts are common events that serve as a powerful tool for cancer diagnosis. Gene amplification of cyclin D is found preferentially in esophageal cancer, whereas gene amplification of cyclin E and c-met is frequently associated with gastric cancer. Mutations of the cyclin-dependent kinase inhibitor genes also occur in esophageal and gastric cancers. However, the scenario of multiple gene changes differs depending on the two histologic types of gastric cancer, because they may have different genetic pathways. Interestingly, the frequency of genetic instability is also quite different between the two types of gastric cancer. A new strategy of molecular diagnosis for gastrointestinal cancers, which started as routine work at Hiroshima City Medical Association Clinical Laboratory last August, may provide a new approach to cancer diagnosis for the next decade. PMID- 7889468 TI - Clinical significance of epidermal growth factor (EGF), EGF receptor, and c-erbB 2 in human gastric cancer. AB - The EGF stimulation system for growth regulation is implicated in normal and neoplastic cell proliferation. The role of EGF, the EGF receptor, and c-erbB-2 in human gastric cancer is reviewed on the basis of several reports, which have been mainly oriented toward their clinical significance. EGF has been shown immunohistochemically to be present in 26% of gastric cancers (n = 395). The presence of EGF in gastric cancer is correlated with the degree of gastric wall invasion and lymph node metastasis. The 5-year survival of patients with EGF positive tumors is worse than that of patients with EGF-negative tumors. The presence of EGF in human gastric cancer may therefore represent a higher malignant potential. Fifteen percent of gastric cancers (n = 352) were also shown to be positive for both EGF and the EGF receptor immunohistochemically, and the simultaneous occurrence of EGF and the EGF receptor suggests that these tumors grow in an autocrine fashion. Tumors exhibiting EGF and the EGF receptor simultaneously show a greater degree of local invasion and lymph node metastasis. Increased expression of EGF receptor protein in gastric cancer appears to be related to biologic aggressiveness, although gene amplification has occurred only to a small extent. Twelve percent of gastric cancers (n = 486) were found to be positive for c-erbB-2. This type of tumor has a frequent metastasis, and patients with c-erbB-2-positive cancer have a poorer prognosis than those with c-erbB-2 negative tumors. Selective blockade of the EGF receptor and c-erbB-2 from their ligands with monoclonal antibodies (MoAbs) inhibits the growth of human gastric cancer xenografts. These MoAbs may therefore be effective antitumor agents against gastric cancer showing overexpression of EGF receptors or c-erbB-2. PMID- 7889469 TI - Duodenogastric reflux and foregut carcinogenesis. AB - Epidemiologic cohort studies have established that after distal gastric resection, there is a higher risk of gastric carcinoma. It is likely that a main factor of this higher risk is the excessive duodenogastric reflux induced by surgery, because the incidence of stump carcinomas is higher in Billroth II than in Billroth I, and most of the stump carcinomas are located near the stoma. In addition, several groups of investigators have suggested that duodenogastric reflux per se induces stump carcinomas in rats. There is another human duodenogastric reflux, the primary duodenogastric reflux, through the pylorus. Experiments in animals have demonstrated that this type of duodenal reflux also induces gastric carcinomas in the antrum of the stomach that has not undergone surgery. Recent clinical attention has focused on the role of duodenogastric reflux in the pathogenesis of Barrett's esophagus and subsequent esophageal adenocarcinomas. Experimentally, reflux of duodenal contents into the esophagus can cause not only Barrett's esophagus and subsequent adenocarcinomas, but also squamous cell carcinomas. These findings suggest that duodenogastric reflux may be implicated in gastric and esophageal, that is, foregut carcinogenesis. PMID- 7889470 TI - Chemoprevention of digestive organs carcinogenesis by natural product protocatechuic acid. AB - The worldwide increase in cancer mortality demands a practical and effective chemopreventive approach to this problem. Using animal bioassay, the authors demonstrated protocatechuic acid (PCA, 3,4-dihydroxybenzoic acid), a simple and antioxidative phenolic acid present in fruits, vegetables, and nuts, to be an efficacious agent in reducing the carcinogenic action of 4-nitroquinoline 1-oxide in oral cavity, N-methyl-N-nitrosourea in glandular stomach, azoxymethane in colon, and diethylnitrosamine in liver. PCA exerts its chemopreventive action partly through inhibition of cell proliferation induced by carcinogens in the target organs. The prospect of this agent as chemopreventive against human cancer warrants a thorough investigation, such as dose-dependent efficacy and its potential toxicity at an effective dose level in other species of animals. Considering its promising anticarcinogenic potency, proliferation biomarkers, including tissue and blood polyamine levels, might eventually be useful in assessing the possible role of PCA intake in high risk populations for cancers of these organs. PMID- 7889471 TI - Carcinogenesis and histogenesis of esophageal carcinoma. AB - Dysplasia is one of the most important subjects regarding carcinogenesis of the esophagus, because there is continuing controversy as to whether esophageal dysplasia is a cancerous lesion or a noncancerous lesion. In this study, it is histopathologically shown that dysplasia has a close correlation with cancer itself and that there is no substantial difference in the cell proliferative activity of dysplasia and intraepithelial carcinoma. These findings thus show that dysplasia has as high a potential for malignancy, thus it should be treated as an extremely early cancerous lesion of the esophagus to substantially improve the long term results of this disease. Conversely, esophageal carcinoma with glandular and/or mucus-secreting components is commonly found in addition to the ordinary component of squamous cell carcinoma, which indicates that this type of esophageal tumor originates not only from the squamous epithelium but also from the esophageal mucus gland or the ductal epithelium. These findings support the concept of field carcinogenesis in esophageal carcinoma. PMID- 7889472 TI - The overexpression of elongation factor 1 gamma mRNA in gastric carcinoma. AB - BACKGROUND: Elongation factor 1 gamma (EF1 gamma) has been isolated from a pancreatic cancer cell line, while the overexpression of EF1 gamma has also been observed in colorectal carcinomas and adenomas. There is, however, still little information on the expression of EF1 gamma in gastric carcinoma. METHODS: The authors examined the expression of EF1 gamma mRNA in 30 gastric carcinomas and their corresponding paired adjacent normal mucosae obtained during surgery while also examining 10 human digestive tract carcinoma cell lines using Northern blot hybridization. RESULTS: An overexpression was observed in 22 (73%) of 30 gastric carcinomas, relative to the corresponding normal tissue. In a clinicopathologic study, no relationship was observed between the overexpression of EF1 gamma mRNA and the histologic grading or depth of tumor invasion. However, 15 (68%) of 22 overexpressed cases were positive for vascular permeation, whereas only 1 of 8 nonoverexpressed cases was positive for vascular permeation, and the difference was significant (P < 0.05). Nine (90%) of 10 with more than a 10-fold overexpression relative to the corresponding normal tissue showed severe vascular permeation in the histologic specimens. Conversely, the expression of EF1 gamma was observed not only in the pancreatic and gastric carcinoma cell lines, but also in the hepatic, ileocecal, duodenal, and colon carcinoma cell lines. CONCLUSIONS: The overexpression of EF1 gamma mRNA was observed in both the gastric carcinoma tissue and in all the other cell lines examined. This probable correlation with vascular permeation in gastric carcinoma is thus considered to provide another piece of useful pathologic information. PMID- 7889473 TI - 10.5-kb homozygote of tumor necrosis factor-beta gene is associated with a better prognosis in gastric cancer patients. AB - BACKGROUND: In NcoI restriction fragment length polymorphism analysis of tumor necrosis factor-beta (TNF-beta) gene, the frequency of 10.5-kb homozygote is low in patients with lung cancer and is associated with a better prognosis. These results should be examined in other malignancies. METHODS: Using polymerase chain reaction, the authors performed NcoI restriction fragment length polymorphism analysis in 152 patients with gastric cancer, in 69 patients with benign gastric lesion, and in 141 healthy volunteers. RESULTS: In 3-year survival, the 10.5-kb homozygote showed a better prognosis (87.1%) than other alleles (5.5-kb homozygote, 52.5%; heterozygote, 79.1%), and there was a statistically significant difference between the 10.5-kb homozygote and the 5.5-kb homozygote. In 3-year survival for Stages III and IV, the 10.5-kb homozygote also showed a better prognosis (64.9%) than other alleles (5.5-kb homozygote, 16.7%; heterozygote, 41.4%). There were statistically significant differences (10.5-kb homozygote vs. 5.5-kb homozygote, P < 0.01; heterozygote vs. 5.5-kb homozygote, P < 0.05). There was a statistical difference between all patients and Stages III and IV (P < 0.05). CONCLUSIONS: The 10.5-kb homozygote of TNF-beta gene is associated with a prolonged survival in patients with gastric cancer, as has been shown in the patients with lung cancer. PMID- 7889474 TI - Growth pattern and p53 overexpression in patients with early gastric cancer. AB - BACKGROUND: The growth pattern of early gastric carcinoma, based on a volumetric analysis, reflects well biologic characteristics of the tumor. The penetrating growth (Pen) type tumor has an unfavorable prognosis, compared with a superficially spreading (Super) type. Abnormality of the p53 suppressor gene plays an important role in alteration of cells leading to development of cancer. p53 point mutations are present even in an early stage of carcinoma. METHOD: In 159 patients with early gastric carcinoma, overexpression of p53 was studied immunohistochemically, using a monoclonal antibody (PAb 1801), and the relationship between growth pattern and p53 overexpression was analyzed. RESULTS: Early gastric carcinoma was grouped into 43 of the Super type, 37 of the expansively penetrating growth (Pen-A) type, 16 of the infiltratively penetrating growth (Pen-B) type, and 63 of the Small mucosal type limited to the mucosal layer. The Pen-A type tumors were characterized by the highest incidence of p53 positive expression and poorest postoperative course. Between the Pen-A type and the Super type, there were significant differences in the incidence of the p53 positive expression (43% vs. 16%), the frequency of recurrence (16% vs. 7%), and disease free interval (574 days vs. 2926 days). CONCLUSION: The authors' observations show that the p53 gene plays an important role in expansion of gastric carcinoma, even in the early stages. PMID- 7889475 TI - Expression of amphiregulin in human gastric cancer cell lines. AB - BACKGROUND: Amphiregulin (AR) is a novel gene of the epidermal growth factor (EGF) family. The authors have already reported that AR mRNA was expressed by human gastric carcinoma cells at various degrees, and its expression was induced by the treatment with EGF or transforming growth factor-alpha (TGF-alpha). METHODS: To elucidate the biologic role of AR in the stomach carcinogenesis, the effect of AR on the cell growth and the expression of growth factor/receptor genes in TMK-1 and MKN-28 gastric carcinoma cell lines was examined. Furthermore, to determine whether AR acts as an autocrine growth factor for gastric carcinoma cells, the authors introduced an antisense phosphorothioate oligodeoxynucleotide (S-oligo) against AR mRNA to these two cell lines. RESULTS: AR stimulated the growth of TMK-1 and MKN-28 cells in a dose dependent manner. The growth-promoting effect of AR was as potent as that of EGF or TGF-alpha. AR antisense S-oligo induced significant growth inhibition of both TMK-1 and MKN-28 cells compared with the control random S-oligo. Moreover, AR induced mRNA expression for AR itself, TGF-alpha, and EGF receptor in both cell lines. CONCLUSIONS: These results overall suggest that AR acts as an autocrine growth factor for these two gastric carcinoma cell lines and evokes the cascade induction of EGF and the TGF alpha/receptor system. PMID- 7889476 TI - Retrovirally transmitted gene therapy for gastric carcinoma using herpes simplex virus thymidine kinase gene. AB - BACKGROUND: Herpes simplex thymidine kinase (HTK) is known to phosphorylate ganciclovir (GCV). Phosphorylated GCV is incorporated into genomic DNA, which leads to inhibition of cell growth and cell death in the replicating cells. Recently, much attention has been drawn to the use of retrovirally mediated gene therapy using HTK as a new therapeutic approach for brain tumors. However, little is known about this phenomenon in gastrointestinal carcinomas. METHODS: The authors transfected the HTK gene packaged in retroviral vector into TMK-1 gastric carcinoma cells (TMK-HTK cells). Sensitivity of TMK-HTK cells to GCV was examined in vitro. Moreover, TMK-HTK cells were transduced into nude mice subcutaneously, and the effects of GCV therapy was examined at the concentration of 20 mg/kg daily for 14 days. RESULTS: TMK-HTK cells were sensitive to GCV at the concentration of 0.1 to 100 micrograms/ml in a dose- and time-dependent manner in vitro. Moreover, 12 of 13 TMK-HTK tumors, which were transduced into nude mice subcutaneously, shrunk from the average diameter of 6.5 mm. CONCLUSION: The results indicate that retrovirally transmitted gene therapy with GCV may provide a new therapeutic approach for treatment of gastric carcinomas. PMID- 7889478 TI - Infiltration of dendritic cells into regional lymph nodes in gastric cancer. AB - BACKGROUND: Dendritic cells (DC), including epidermal Langerhans cells, are potent antigen-presenting cells that can carry and present tumor antigens to helper T-cells. An immunohistochemical study was performed to clarify the relationship between the extent of infiltration by DCs in primary gastric cancer and that in the regional lymph nodes. METHODS: Paraffin blocks were prepared for staining with antibody against S-100 protein in 121 cases of gastric cancer. Infiltration of S-100 protein-positive DCs was evaluated in the primary tumor and in the peritumoral, primary, secondary, and tertiary nodes. RESULTS: The extent of infiltration by DCs into the regional lymph nodes decreased significantly with an increasing distance of the nodes from the primary tumor. Correlation of the extent of such infiltration was observed among the peritumoral, primary, secondary, and tertiary nodes. However, the extent of infiltration into the primary tumor did not correlate with that into the primary, secondary, and tertiary nodes. Infiltration by DCs of the peritumoral nodes correlated with that of the tumor, particularly when lymph node metastasis was absent. There was no significant difference in the extent of infiltration into the peritumoral nodes even when lymph nodes were involved. However, infiltration of DCs increased in the primary and secondary nodes when the primary nodes were involved. CONCLUSION: Infiltration of DCs may be regulated in the primary lesion of gastric cancer. The peritumoral lymph nodes serve as transmitters of DCs from the primary tumor to the regional lymph nodes. DCs in the regional lymph nodes are important for establishing immunologic defense mechanisms in cases of gastric cancer when metastasis is absent or limited to the primary nodes. PMID- 7889477 TI - Mucosal IgA antibody against Helicobacter pylori in chronic gastritis and intestinal metaplasia detected by the Tes-Tape method in resection specimens after gastrectomy for gastric cancer. AB - BACKGROUND: Subjects with atrophic body gastritis have a high prevalence of Helicobacter pylori seropositivity and a low prevalence of H. pylori infection. Disappearance of the organism appears to correlate with the development of intestinal metaplasia. To investigate this point, intestinal metaplasia was biochemically subclassified into complete and incomplete types by the Tes-Tape method, and tissue IgA and IgG antibodies against H. pylori were measured by enzyme-linked immunosorbent assay (ELISA). METHODS: Twenty-five stomachs resected for gastric cancer were examined using the Tes-Tape method. Serum H. pylori IgA and IgG antibodies and tissue IgA and IgG antibodies against H. pylori and tissue secretory IgA (sc-IgA) were examined in areas of intestinal metaplasia, nonmetaplastic gastric mucosa, and gastric carcinoma by ELISA: RESULTS: Tissue H. pylori IgA antibody was positive in 6 of 19 (32%) specimens taken from complete and 2 of 7 (29%) incomplete types of intestinal metaplasia and was positive in 6 of 14 (43%) nonmetaplastic gastric mucosa from the antrum and 14 of 23 (61%) from the body. Duodenal mucosa and cancer tissue were positive for tissue IgA antibody in 1 of 6 (17%) and 0 of 17 (0%), respectively. Tissue H. pylori IgG antibody was negative in all the tissues examined. sc-IgA in the areas of intestinal metaplasia was 120 +/- 65 (mean +/- standard error; ng/mg wet weight) and in the nonmetaplastic gastric mucosa was 113 +/- 72, showing no difference. Positivity and negativity of serum IgA and IgG antibodies against H. pylori coincided with presence or absence of tissue IgA antibody in nonmetaplastic gastric mucosa in 15 of 19 (79%) and 16 of 19 (84%) patients examined, respectively. CONCLUSION: Positivity rates of tissue IgA antibody against H. pylori were lower in the mucosa of intestinal metaplasia than in nonmetaplastic gastric mucosa and were negative in carcinoma. No significant difference in levels of sc-IgA between intestinal metaplasia and non-metaplastic gastric mucosa was found. PMID- 7889479 TI - The mechanism of human autologous gastric signet ring cell tumor rejection by cytotoxic T lymphocytes in the possible context of HLA-A31 molecule. AB - BACKGROUND: Tumor rejection antigens in human melanomas, which are recognized by cytotoxic T lymphocytes (CTLs), have recently been identified. To elucidate the cytotoxic mechanism in tumors other than melanoma, several pairs of CTLs and tumor lines were established. The authors report that HLA-A31 may present a tumor rejection antigen that is recognized by the human autologous gastric signet ring cell carcinoma-specific CTL. They also briefly describe the in vitro enhancing effect of interferon-gamma (INF-gamma) on the lysis of tumor cells by autologous CTL. METHODS: The MHC Class I-restricted CTL clone, TcHST-2, and autologous gastric signet ring cell carcinoma line, HST-2, were established. Cytotoxicity blocking assays of antibodies reacting against the MHC Class I nonpolymorphic determinant and HLA-A, B, and C haplotype elements, which are expressed on the HST-2 cells, were performed. RESULTS: Lysis of the autologous tumor cells (HST-2) by the CTL clone (TcHST-2) was enhanced when the tumor cells were pretreated with IFN-gamma. This lysis was selectively inhibited by the anti-nonpolymorphic MHC Class I determinant monoclonal antibody (MoAb) and anti-HLA-A31 haplotype specific MoAb. However, TcHST-2 clone was not cytotoxic to HLA-A31+ allogeneic leukemia lines. CONCLUSION: Pretreatment of target cells with IFN-gamma may be a necessary procedure for the efficient lysis of HST-2 cells by autologous TcHST-2 CTL. The data indicate that TcHST-2 was MHC Class I-restricted HST-2 tumor specific CTL and suggest that the HLA-A31 haplotype element is an antigen presenting molecule. Also discussed is the nature of the antigenic peptides in gastric signet ring cell carcinoma. PMID- 7889480 TI - Etiology of gastric remnant cancer with special reference to the effects of denervation of the gastric mucosa. AB - BACKGROUND: Gastric mucosal blood flow, secretion of mucin, and renewal of the gastric mucosal cells are considered to be defensive factors against gastric mucosal injuries. These factors are regulated by the nervous system and neuropeptides. Gastrectomy may affect this regulation and induce gastric mucosal changes, such as atrophic gastritis and carcinoma. The effects of denervation of the gastric mucosa on tumorigenesis of the remnant stomach were investigated. METHODS: Using male Wistar rats, four groups of Billroth I (B-I)gastrectomy, Billroth II (B-II) gastrectomy, and those with denervation were conducted. Subdiaphragmatic truncal vagotomy was performed in the denervated group. Thirty weeks after the operations, histologic examination and periodic acid-Schiff- Alcian blue (PAS-AB) staining of the gastric mucosa, analysis of cell kinetics of the gastric mucosa by immunohistochemistry of proliferating cell nuclear antigen, and measurement of intragastric pH, intragastric bile acid concentration, and serum gastrin levels were performed. No carcinogenic agents were given. RESULTS: The B-I group showed no remarkable gastric mucosal changes, but B-I with denervation showed a significant increase in the development of tumor (67%) and carcinoma (42%). In the B-II groups, the denervation induced a significant increase in tumorigenesis, from 22% to 58%. Analysis of cell kinetics revealed a significant increase of labeling index in those groups that developed tumors. PAS AB staining showed a decrease of PAS positive mucin but an increase of acidic mucin-producing cells in the denervated groups, suggesting an increase in the number of immature cells that are more susceptible to atrophic gastritis and carcinoma. There was no close relationship between tumorigenesis and intragastric pH, intragastric bile acid concentration, or serum gastrin levels. CONCLUSIONS: After gastrectomy, not only duodenogastric reflux, but also the denervation of the gastric mucosa play an important role in the etiology of gastric remnant cancer. PMID- 7889481 TI - Factors influencing growth rate of recurrent stomach cancers as determined by analysis of serum carcinoembryonic antigen. AB - BACKGROUND: Although there are many reports regarding the growth rate of human tumors, those discussing stomach cancer are rare due to the difficulty in evaluating the growth rate of stomach cancer. Stomach cancers grow with either a large central depression or through severe invasion. Metastatic sites of stomach cancer, however, grow expandingly, as with pulmonary tumors. METHODS: The reported doubling time estimate, based on the serum level of carcinoembryonic antigen (CEA), agreed with the actual tumor doubling time investigated in 112 previously untreated patients with recurrent gastric cancers. The influencing factors of the CEA doubling time were studied clinicopathologically, and a possible correlation between postoperative survival and the CEA doubling time was noted. RESULTS: The CEA doubling time ranged from 12 to 105 days, with a mean of 37.5 +/- 20.5 days (mean +/- standard deviation) and a median of 32 days. The CEA doubling time did not differ significantly between sexes or between patients of varying ages. However, the CEA doubling time was significantly shorter in patients with papillary adenocarcinoma than in those with well or moderately differentiated tubular adenocarcinoma. The CEA doubling time of patients with poorly differentiated adenocarcinoma was divided into two groups--a shorter one and a longer one. The doubling time was also significantly shorter in patients with liver metastasis than in those with lymph node metastasis or peritoneal dissemination. Furthermore, among patients who did not receive any chemotherapy, a significant correlation was observed between the CEA doubling time and postoperative survival time. Most treated patients survived longer than untreated patients. CONCLUSION: The influencing factors on growth rates in recurrent stomach cancers were histologic type and metastatic sites. This growth rate plays an important role in determining the degree of biologic malignancy and may be influenced by some chemotherapeutic regimens. PMID- 7889482 TI - Microsatellite instability in Japanese gastric cancer. AB - BACKGROUND: Recent studies have shown that microsatellites are unstable in various types of cancers, and such genetic instability at the microsatellite loci (microsatellite instability) has been considered to play an important role in the development of cancer. However, the clinicopathologic significance of microsatellite instability in gastric cancer has not been clarified. METHODS: To elucidate the role of genetic instability in the development of gastric cancer, the presence of microsatellite instability was examined in 25 cases of gastric cancer using fresh-frozen tumor-normal paired samples using a polymerase chain reaction (PCR)-based method. Microsatellite instability was defined as tumors that showed altered banding patterns at two or more microsatellite loci. RESULTS: The incidence of microsatellite instability in gastric cancer cases was 4 of 25 patients (16%) and 4 of 26 cancers (15%). A significantly high incidence of microsatellite instability was observed in both the elderly (P < 0.01) and in lymph node metastasis-negative patients (P < 0.05). All patients with gastric cancer showing microsatellite instability were negative for lymphatic or venous permeation. A statistically significant association of microsatellite instability with no lymphatic permeation was thus observed (P < 0.05). CONCLUSIONS: This study revealed infrequent lymph node metastasis and lymph vessel invasion in the patients with gastric cancer demonstrating microsatellite instability. Although the number of examined cases was small, these findings suggest that gastric cancer that shows microsatellite instability may thus behave in a less malignant manner. PMID- 7889483 TI - The effects of dietary fiber from Lagenaria scineraria (yugao-melon) on colonic carcinogenesis in mice. AB - BACKGROUND: The increasing trend of colon cancer in Japan is attributed to changes in dietary habits, that is, increased amounts of fat and decreased amounts of fiber in the diet. The effects of Japanese dietary fiber from Lagenaria scineraria (yugao-melon) on colonic carcinogenesis in mice were examined. METHODS: Eighteen ICR mice in each group were fed with either a basal diet or a diet containing 5%, 10%, or 20% of yugao powder for 35 weeks. All the mice received a weekly intraperitoneal injection of 1,2-dimethylhydrazine (DMH), 10 mg/kg body weight for 10 weeks. The effects of yugao powder on the mucosal and luminal variables involved in colonic carcinogenesis were then compared with those of wheat bran in the mice without any carcinogen treatment. RESULTS: The incidence of colon tumors (adenocarcinomas) was lower in the yugao powder diet groups than in the basal diet group at week 35 (24% vs. 50%, P < 0.05). The bile acid concentration in the colon was reduced in all the fiber diet groups except for the 5% yugao powder diet group. The colonic luminal pH acidified as yugao powder contents also increased in the yugao powder diet groups. The findings on the colonic short chain fatty acids, microflora, and mucosal fatty acids and ornithine decarboxylase activity were all inconsistent with a tendency to either develop or to inhibit carcinogenesis in both the fiber diet groups. CONCLUSIONS: Dietary fiber from yugao-melon suppressed DMH-induced colonic carcinogenesis in mice by lowering the bile acid concentration and pH in the colon. The results of the luminal and mucosal variables examined also suggested that the mechanisms of action of yugao powder against colonic carcinogenesis differed from those of wheat brain. PMID- 7889484 TI - Overexpression of matrix metalloproteinase-7 mRNA in human colon carcinomas. AB - BACKGROUND: Matrix metalloproteinase-7 (MMP-7) is a member of the family of matrix-degrading metalloproteinases (MMPs) that are considered to contribute to cancer invasion and metastasis. One of the gene products that the authors have isolated by a cDNA subtraction of human gastric cancer minus normal gastric mucosa is MMP-7. The purpose of this study was to examine the expression of MMP-7 mRNA in different stages of human colorectal carcinomas. METHODS: A subtracted complementary DNA library was generated from a paired sample of human gastric carcinoma minus normal gastric mucosa. Screening of the library clones determined that MMP-7 mRNA was overexpressed. The complementary DNA insert was then used as a probe to evaluate the expression in a larger number of surgical samples of human colorectal carcinomas by Northern hybridization. RESULTS: The mRNA signal was greater in the colorectal carcinoma than in paired adjacent normal colonic or rectal mucosa in 39 of 47 cases. The expression of MMP-7 mRNA in tumor tissues increased with increasing Dukes' stage (P < 0.05). The MMP-7 mRNA expression was greatest in the metastatic liver lesions. CONCLUSIONS: The findings imply that MMP-7 mRNA is overexpressed in human colorectal carcinomas and that MMP-7 may prove useful as a marker of biologic aggressiveness. PMID- 7889485 TI - Mutant K-ras in apparently normal mucosa of colorectal cancer patients. Its potential as a biomarker of colorectal tumorigenesis. AB - BACKGROUND: The best way to reduce the incidence of colorectal cancer mortality would be to prevent this cancer. However, none of the biomarkers proposed can accurately identify persons at increased risk of colorectal cancer or those at low risk. As a possible genetic biomarker, K-ras mutations, which are frequently found in colorectal cancers, were analyzed in apparently normal colorectal mucosa. METHODS: Nonneoplastic mucosa and tumor tissues were collected at surgery from 70 patients with colorectal cancer: one sample each from 50 patients (group A) and multiple samples from the other 20 patients (group B). Mutant K-ras codon 12 was analyzed by the enriched polymerase chain reaction (EPCR), by which one mutant can be detected among 10(3) to 10(4) normal alleles. RESULTS: Only with the aid of EPCR was mutant K-ras detected in nonneoplastic mucosa of nine patients (18%) in Group A and five patients (25%) in Group B. This increased incidence could be attributed to the multiple tissue sampling. The presence of mutant K-ras in nonneoplastic mucosae was not consistently correlated with that in the tumors. These findings suggest that the mutant K-ras identified in nonneoplastic mucosa actually represents de novo mutations, which may be initiated by different etiologic factors and at different times. CONCLUSION: Mutant K-ras detected in apparently normal mucosa should be a useful biomarker for identifying persons at higher risk of colorectal cancer. Our study also emphasizes the need for improving the method for sample collection to achieve true representation of the colorectal mucosa. PMID- 7889486 TI - Frequent and characteristic K-ras activation in aberrant crypt foci of colon. Is there preference among K-ras mutants for malignant progression? AB - BACKGROUND: To investigate very early lesion of colorectal cancer, K-ras activation and nuclear p53 accumulation were studied in aberrant crypt focus (ACF). METHODS: ACF were microscopically identified in grossly normal mucosa of patients with colorectal cancer who underwent surgery. Each ACF was microdissected from the surgical specimen and divided into two pieces, one for histologic and immunohistochemical examinations and the other for K-ras activation. K-ras mutations in codons 12 and 13 were sequenced after being screened by polymerase chain reaction amplification followed by restriction fragment length polymorphism analysis. Intranuclear accumulation of p53 protein was immunostained with the avidin-biotin complex method. RESULTS: ACF was predominantly distributed in the sigmoid colon and rectum, and its incidence was increased with age. Unexpectedly, ACF was very rare in colons of three patients with hereditary nonpolyposis colorectal carcinoma. K-ras mutations were detected in 58% (33 of 57) of ACF cases and in 44% (11 of 25) of adenocarcinoma cases. Although GTT mutation in codon 12 was predominantly observed in adenocarcinoma (10 of 11), GAT mutation (12 of 33) was as frequent as GTT mutation (11 of 33) in ACF together with mutation at codon 13 (7 of 33). No accumulation of p53 protein was found in any ACF. CONCLUSION: ACF were not diagnosed as neoplasms histologically, but they were considered to be neoplastic lesions, and K-ras activation is one of the key events to form ACF. The G-T substitution in K-ras codon 12 may undergo malignant growth easily compared with G-A substitution in colorectal carcinogenesis. PMID- 7889487 TI - How do colorectal cancers develop? AB - BACKGROUND: The aim of this study was to reveal (1) whether a flat adenoma is the precursor of a flat cancer and (2) the more frequent pathway in colorectal cancer development-a flat cancer or a polypoid cancer. METHODS: Clinical features and histologic characteristics of 97 flat early cancers, 138 polypoid early cancers, 60 advanced cancers involving the muscularis propria, and 185 flat adenomas were investigated. RESULTS: Of the flat cancers, 89.7% were not accompanied by residual adenoma and are considered to have arisen de novo. The distribution of flat adenomas and flat cancers was significantly different, and a follow-up of flat adenomas did not reveal any rapid growth or carcinomatous changes in the flat adenomas. The shape of advanced cancers involving only the muscularis propria almost matches that of flat early cancers. Fifty-two of 97 flat cancers and 19 of 138 polypoid cancers invaded the submucosal layer. CONCLUSIONS: Flat adenomas are not considered to be precursors of flat cancers. Advanced cancers of the large intestine originate mainly from flat cancers arising de novo. The percentage of the advanced cancers that originate from flat cancers is estimated to be 71.2% (52 of 52 +/- 19) at a minimum. PMID- 7889489 TI - Characterization and biodistribution of a mouse/human chimeric antibody directed against pancreatic cancer mucin. AB - BACKGROUND: Nd2 is a murine monoclonal antibody (MoAb) directed against purified mucins of the human pancreatic cancer cell line SW1990. The authors previously reported promising results with Nd2 for immunotargeting pancreatic cancer. However, murine MoAbs induce human anti-mouse antibodies (HAMAs), a serious problem for clinical use. Mouse/human chimeric antibodies may be less immunogenic and therefore reduce the incidence of HAMAs. In this study, the binding affinity, tumor specificity, biodistribution, and immunoimaging of chimeric Nd2 were evaluated. METHODS: The affinity of chimeric Nd2 was evaluated by competition radioimmunoassay and Scatchard analysis using 125I-chimeric Nd2, 125I-murine Nd2, and SW1990 mucin. Immunoreactivity against pancreatic cancer tissues was examined histochemically by the avidin-biotin peroxidase complex method. The biodistribution of the MoAbs was examined in athymic nude mice bearing SW1990 xenografts that were administered intravenous 125I-labeled chimeric or murine Nd2. 111In-chimeric Nd2 was injected into the same xenograft models, and scintigrams were obtained on day 3. RESULTS: Affinity analysis and immunohistochemical studies showed that chimeric Nd2 had the same affinity to SW1990 mucin and the same specificity for pancreas cancer tissues as murine Nd2. Intravenous administration of 125I-chimeric Nd2 resulted in a maximum tumor accumulation of 43% of the initial dose/gram of tumor, which was almost identical to the accumulation of 125I-murine Nd2. Distinct immunoscintigrams of tumors in nude mice were obtained with 111In-chimeric Nd2. CONCLUSION: Chimeric Nd2 may have clinical potential in the radioimmunodetection and immunotherapy of pancreatic cancer. PMID- 7889488 TI - Fucosyltransferase of the peritoneum contributed to the adhesion of cancer cells to the mesothelium. AB - Adhesion molecules associating with peritoneal dissemination were investigated using human gastric (MKN45 and MKN74) and colon (KM12C and KM12SM) cancer cells and the mouse peritoneum. Adhesion of cancer cells to the peritoneum was determined by a recently reported novel ex vivo method. MKN45 cells established from poorly differentiated adenocarcinoma with less glycosylated sugar chains on their cell surface showed higher adhesion activities to the peritoneum ex vivo and produced large amount of metastases in the abdominal cavity of nude mice, whereas MKN74 cells from differentiated adenocarcinoma with more glycosylated sugar chains showed slightly low adhesion activity. KM12SM cells with highly metastatic potential to liver showed fairly low adhesion activity to the peritoneum compared with KM12C cells. The mouse peritoneum was found to contain alpha 1 --> 2, alpha 1 --> 3, and alpha 1 --> 4 fucosyltransferases, and adhesion of cancer cells was observed to the cellulose ester membrane, on which partially purified alpha-fucosyltransferases from mouse peritoneum were immobilized. The adhesion of cancer cells to fucosyltransferase-immobilized membrane was specifically inhibited by the addition of oligosaccharides and glycoproteins, which could serve as substrates for alpha-fucosyltransferases. These results indicate the contribution of alpha-fucosyltransferases to the adhesion of disseminated cancer cells to the peritoneum and support the possibility of antiadhesion therapy of peritoneal dissemination by treatment with substrates for alpha-fucosyltransferases. PMID- 7889491 TI - Sixteenth Annual Interdisciplinary Cancer Research Workshop. PMID- 7889490 TI - Characterization of cancer cell dissociation factor in a highly invasive pancreatic cancer cell line. AB - BACKGROUND: Two pancreatic cancer cell lines, the highly invasive and metastatic cell line PC-1.0 and the weakly invasive and rarely metastatic cell line PC-1, were established from a pancreatic ductal carcinoma induced by N-nitrosobis (2 oxopropyl) amine in a Syrian golden hamster. METHODS: The cancer cell dissociation activity in serum-free conditioned medium of PC-1.0 cells was partially purified using a heparin column, a hydroxylapatite column, anion exchange, and gel filtration high-performance liquid chromatography. Several biologic properties of the partially purified activity were evaluated. RESULTS: Two cell lines exhibited different growth morphologic changes in vitro: the weakly invasive cell line PC-1 formed islandlike colonies, and the highly invasive cell line PC-1.0 grew mainly as single cells. The conditioned medium of PC-1.0 cells induced dissociation of islandlike colonies and morphologic changes of PC-1 cells to elongated cells, with a high frequency of pseudopodia formation similar to the morphologic findings of PC-1.0 cells. The dissociation activity did not bind to the heparin column and had an apparent molecular mass of > 400 kDa, as deduced from gel filtration. Several immunoreactive proteinous bands were observed in immunoblotting analysis using a polyclonal blocking antibody. The partially purified activity enhanced cell motility, chemoinvasion, and cell adhesion to plastic plates and fibronectin. CONCLUSIONS: Highly invasive and metastatic PC-1.0 cells produce a soluble proteinous factor, called "dissociation factor" (DF), which induces cell dissociation of weakly invasive and rarely metastatic PC-1 cells. It seems likely that DF has a role in tumor invasion and metastasis. PMID- 7889492 TI - Canine U2 snRNA gene: nucleotide sequence, characterization and implications in RNA processing and cancer biology. AB - Abnormal RNA processing (splicing) may lead a cell to become cancerous. Transcription of a gene starts in the nucleus where genomic DNA is converted to precursor RNA by removing introns and joining exons. Splicing, mediated by small nuclear RNA (snRNA) and nuclear proteins, is tightly regulated during growth and development. U2 snRNAs are small, stable RNAs located in the nucleus of eukaryotic cells that recognize the branch point of the intron-exon junction. We describe here the organization of DNA sequences complementary to canine U2 snRNA. From a genomic library we isolated one recombinant containing the U2 gene. Southern analysis revealed that the canine species possesses only 3 to 5 U2 snRNA genes or very closely related sequences. The size of the U2 gene is 125 nt whereas in rat, Drosophila, trypanosome and yeast it is 189, 234, 141, and 192 nt respectively. The nucleotide sequence showed 82, 78, 72 and 95% homology with rat, Drosophila, yeast, and trypanosome U2 snRNA, respectively. The sensitivity of U2 snRNA towards alpha-amanitin suggests that it is transcribed by RNA polymerase II. The conserved nucleotide sequences which have been implicated in heterogeneous nuclear RNA splicing have been identified. The implications of the knowledge gained through above studies in cancer biology are discussed. PMID- 7889493 TI - Elevated serum Lp(a) levels in the early and advanced stages of breast cancer. AB - Recently, lipoprotein (a) [Lp (a)] levels were found to be elevated in various types of cancer. This study was designed to evaluate the role of serum Lp (a) in early and advanced stages of breast cancer. Fasting venous blood samples were collected from 18 patients with Stage I, and 21 patients with Stage IV disease and were analysed for Lp (a). The results were compared with data from 22 healthy female controls. Patients with both Stage 1 and Stage IV disease had significantly higher (p < 0.001) Lp (a) concentrations than did healthy controls. Lp (a) was also found to be significantly elevated in Stage IV patients when compared with the Stage I group. Our data suggest that there is a highly significant association between Lp (a) and the presence and progression of breast cancer, and the serum Lp (a) determination may provide an aid in patients with breast cancer for both diagnostic purposes and the follow-up of the disease. PMID- 7889495 TI - Serum N-acetyl-beta-glucosaminidase activity in breast cancer. AB - N-acetyl-beta-glucosaminidase (NAG) and its isoenzymes were measured in 60 patients with breast cancer and in 30 patients suffering from benign breast tumors. NAG activity was significantly increased (P < 0.001) in cancer patients. The concentration of isoenzyme A always exceeded that of isoenzyme B, but isoenzyme B concentration was significantly (p < 0.001) higher in patients than in controls. An intermediate form, I, was more evident but not significant in patients. Evaluation of the predictive value of the NAG isoenzyme B, revealed a good sensitivity, efficiency and specificity. It seems from this study that the determination of the isoenzyme NAG B activity may be useful for better diagnosis of breast cancer. PMID- 7889494 TI - Experimental combination chemotherapy of pirarubicin with various antitumor drugs against P388 murine leukemia. AB - We have examined the therapeutic effects of combination therapy of pirarubicin ((2"R)-4'-O-tetrahydropyranyladriamycin, THP) with various antitumor agents against P388 murine leukemia. THP showed a high antitumor activity in combination with various antitumor drugs, especially with cyclophosphamide (CPM), cisplatin (CDDP), mitomycin C (MMC), enocitabine (BHAC), vindesine (VDS) or methotrexate (MTX). The effects of combination therapy depended on the order of administration of THP and combined drugs. THP-preceding treatment gave more synergistic effects in combination with 5-fluorouracil (5-FU) or MTX. THP-preceding or simultaneous treatment with etoposide (ETP) indicated the higher synergistic activity than ETP preceding one. Moreover, THP showed much higher synergistic effects in any order of the combination with CPM, CDDP, MMC, BHAC, VDS or MTX. These results suggest that THP possesses a therapeutic usefulness clinically in combination with various antitumor drugs, if the selection of drugs combined with THP and the order of administration are suitable. PMID- 7889496 TI - Q-modification of tRNAs in human brain tumors. AB - Queuosine (Q nucleoside) is a highly modified guanosine analog and is present only in the first position of the anticodons of tRNA(Tyr), tRNA(His), tRNA(Asn) and tRNA(Asp). The levels of Q in normal human brain and two different types of human brain tumors (meningiomas and astrocytomas) were determined by using an enzymatic assay method. tRNAs isolated from tumor tissues contained decrease amounts of Q when compared to tRNAs from normal (i.e. non-tumor) brain tissue. There was a relationship between the levels of Q nucleoside and the tumor malignancy in the sense that the deficiency was greater in the highly malignant astrocytomas compared to meningiomas which are usually benign tumors. Increased Q deficiency was also observed in higher grade tumors. PMID- 7889497 TI - Inhibition of cultured leukemia cell growth by enhanced adriamycin cytotoxicity with reduction of glutamine or asparagine level in medium. AB - The effect of a singular amino acid, asparagine (Asn), glutamine (Gln), or proline deletion in a cultured medium (RPMI 1640 supplemented with 10% fetal calf serum and other ingredients) on adriamycin (ADR) cytotoxicity was evaluated in the growth of P388 murine leukemia cells and CEM human acute lymphoblastic leukemia cells over a 3 day period. No enhancement of ADR cytotoxicity was observed in the assay of IC50 values under the amino acid deleted condition. Singular deletion of Gln or Asn from ADR-free medium apparently inhibited the proliferation of both cells, i.e. both cell lines strongly require them. The cytotoxicity of 5 nM ADR was then examined in medium which included one or the other of them in stepwise levels varied at 80, 60, 40, 20 and 0% of the ordinary level. Change of Asn level caused a difference in ADR toxicity; also, the change of Gln level, especially the 60% level caused ADR toxicity of 5 nM, which is less than the IC50 value, in the proliferation of both cells. This suggested the usefulness of glutamine level modification on the enhancement of ADR cytotoxicity. PMID- 7889499 TI - Chromosome abnormalities and p53 expression in a small cell carcinoma of the bladder. AB - Chromosome studies on a highly malignant tumor, a small cell carcinoma of the bladder (the first to be studied cytogenetically), showed a hypertriploid mainline and a hypertetraploid minor line. Extensive chromosomal rearrangements were present in both lines, some rearranged chromosomes being seen in only one of the lines, while others, derived from chromosomes 6, 9, 11, 13, and 18, were seen in both. Although different giant chromosomes were present in the two lines, they shared a possibly significant common feature: multiple copies of 2q. DNA flow cytometry confirmed that the tumor had a hypertriploid main mode and showed that dysplastic surface epithelium present in the histologic material also had a hypertriploid DNA index. p53 expression in the tumor was demonstrated by flow cytometry. PMID- 7889498 TI - Deletion 6q in three cases of mixed-type liposarcoma in addition to t(12;16)(q13;p11) AB - We report the cytogenetic findings in three mixed liposarcoma following short term cultures. During the course of cytogenetic investigation of various types of liposarcomas, we observed an interstitial deletion of the long arm of chromosome 6 together with the translocation (12;16)(q13;p11) in three tumors. Translocation (12;16) is associated with myxoid and mixed (myxoid/round cell) liposarcomas, although deletion of chromosome 6 has been observed in only a few of these tumors. Our findings suggest that del(6), as an additional change in myxoid liposarcoma, is probably related to tumor progression. PMID- 7889500 TI - Cytogenetic and flow cytometric analysis of a pancreatoblastoma. AB - A pancreatoblastoma from a 4-year old male was examined by flow cytometric ploidy analysis and cytogenetics. To detect differences within the tumor, the specimen was divided into four portions and sampled separately. Flow analysis revealed that each sample contained a diploid and a tetraploid population of tumor cells. These findings correlated well with the cytogenetic analysis, which also revealed differences in structural rearrangements between samples. A t(13;22)(q10;q10) was the only rearrangement found in near-diploid cells as well as one near-tetraploid line. Other common structural changes in near-tetraploid cells included t(13;13)(q10;q10), i(6p)(p10), and del(1). Chromosomes 1, 6, 13, and 22 were consistently missing from all near-tetraploid cells lines. To our knowledge, this is the first flow cytometric and cytogenetic study of a pancreatoblastoma. PMID- 7889501 TI - Near-haploidy in two malignant fibrous histiocytomas. AB - Cytogenetic analysis of two malignant fibrous histiocytomas (MFH) revealed near haploid clones in both tumors. One tumor had only 23 chromosomes, the lowest chromosome number so far detected in human neoplasia, and showed several structural rearrangements: 23, X, der(1)t(1;?;8)(q42;?;q13), +del(7)(p11),der(8)t(8;13)(q13;q12), inv(9)(p24q21), r(10)(p15q26), -13, der(14)t(14;22)(p13;q11), -15, +r. The other MFH had only numerical changes: 28,X, +5, +18, +20, +21, +22/56, idemx2. With the present two cases, four of 78 MFHs studied in our laboratory have been near-haploid, suggesting that this otherwise rare phenomenon in neoplasia may be relatively common in MFH. PMID- 7889502 TI - Chromosomal instability in multiple endocrine neoplasia type 1. Cytogenetic evaluation with DEB test. AB - Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant condition with high penetrance and variable expressivity, in which tumors or hyperplasia occur in two or more endocrine organs. Some authors have investigated chromosomal instability in MEN 1 and MEN 2; the results are controversial. Chromosome analyses were performed on lymphocytes from seven patients with MEN 1, four healthy first-degree relatives (three of whom were children), six phenotypically normal volunteers, and three patients with Fanconi's anemia. To evaluate chromosomal instability we analyzed phytohemagglutinin-stimulated lymphocyte cultures with and without diepoxibutane. We observed an increase in the frequency of spontaneous chromosomal alterations in four patients. After the DEB test we found an increase in chromatid breakages, gaps, and exchange figures. These findings support the inclusion of the MEN 1 syndrome among the disorders with "chromosomal instability." PMID- 7889503 TI - Supernumerary isochromosome 4p in ANLL-M4 myelomonocytic type is associated with favorable prognosis. AB - A case of an acute non-lymphocytic leukemia of M4 type with a supernumerary isochromosome (4p) in 100% of the initial bone marrow metaphase cells is reported. The origin of the extra chromosome is verified by the fluorescence in situ hybridization technique using a whole chromosome 4 painting probe. A possible favorable prognosis of the ANLL-M4 case showing a supernumerary isochromosome (4p) is cautiously emphasized. PMID- 7889504 TI - Translocation (2;3)(p22;q28) is associated with myeloid disorders. AB - Chromosome studies carried out in two children with acute myeloblastic leukemia (AML, M2) showed a t(2;3)(p22;q28). This abnormality was associated with monosomy 7 and del(12)(p12) in the first patient and was found only in relapse in the second patient. Comparison with the other previously published t(2;3) suggests that this translocation is a nonrandom abnormality involving a pluripotent stem cell and occurring as a secondary chromosome abnormality in AML. PMID- 7889505 TI - Are chromosome aberrations in circulating lymphocytes predictive of future cancer onset in humans? Preliminary results of an Italian cohort study. AB - To investigate the existence of an association between the frequency of chromosome aberrations (CA) in non-target tissues and cancer risk, a historical cohort study was carried out in a group of 1455 subjects screened for CA over the last 20 years in Italy. Statistically significant increases in standardized mortality ratio (SMR) for all cancers were found in subjects with medium and high levels of CA in peripheral blood lymphocytes (SMR = 178.5 and SMR = 182.0, respectively) and in subjects with high levels of CA for respiratory tract cancers (SMR = 250.8) and lymphatic and hematopoietic tissue neoplasms (SMR = 548.8). Significant trends in the SMRs were observed for these latter causes of death. PMID- 7889506 TI - Translocation (6;10)(p21;q22) in uterine leiomyomas. AB - A translocation between chromosomes 6 and 10 was observed in two uterine leiomyomas. Translocation (6;10) may be important in the pathogenesis of a subgroup of uterine leiomyomas. PMID- 7889507 TI - Chromosome aberrations in desmoid tumors. Trisomy 8 may be a predictor of recurrence. AB - Cytogenetic analyses of short-term cultures revealed clonal chromosome aberrations in 6 of 13 desmoid tumors. These aberrations included two consistent events, trisomy 8 (n = 4) and trisomy 20 (n = 3), which have not been reported previously in desmoid tumors. Because trisomy 8 was found in two recurrent desmoid tumors, we used fluorescent in situ hybridization (FISH) methodology to evaluate chromosome 8 in 25 paraffin-embedded and frozen desmoid specimens. The FISH studies demonstrated that both patients with cytogenetic trisomy 8 at the time of recurrence also had had trisomy 8 in primary tumors 4 years earlier. The proportion of trisomy 8 cells in these cases did not change substantially between original diagnosis and recurrence. The FISH studies also revealed trisomy 8 in one recurrent desmoid tumor which had been cytogenetically unremarkable and revealed trisomy 8 in one recurrent desmoid that had not been karyotyped. Four of six patients with trisomy 8 had been followed for more than 1 year, and the desmoid tumors in each of these 4 patients recurred. By contrast, recurrence was noted in only 2 of 17 patients whose desmoid tumors lacked trisomy 8. Our findings demonstrate that trisomy 8 and trisomy 20 are nonrandom aberrations in desmoid tumors. Trisomy 8 appears to be associated with an increased risk of recurrence. PMID- 7889510 TI - Fluorescence in situ hybridization for the detection of trisomies 8 and 9 in polycythemia vera. AB - Trisomies 8 and 9 are the most common numerical chromosome abnormalities in polycythemia vera (PCV). Their role in the pathogenesis of the disease is unclear, however, as is their diagnostic or prognostic value. We evaluated fluorescent in situ hybridization as compared to chromosome analysis for the detection of trisomies 8 or 9 in peripheral blood cells of PCV patients. We demonstrated that FISH is a more sensitive method for the detection of the abnormalities. A positive correlation between the duration of the disease and trisomy 9 was found. FISH is a sensitive, convenient, and rapid method for the diagnosis and follow-up of chromosome aberrations in patients with PCV. The application of FISH to a larger cohort of patients may provide valuable information regarding the role of the chromosomal aberrations in the initiation and progression of this disease. PMID- 7889508 TI - Monosomy 1p is correlated with enhanced in vivo glucose metabolism in meningiomas. AB - The 2-[18F]fluoro-2-deoxy-D-glucose (FDG) uptake of 25 human meningiomas was preoperatively evaluated in vivo by positron-emission tomography (PET). After surgery, meningioma biopsies were analyzed cytogenetically. Five meningiomas showed partial monosomy for chromosome 1p additional to other typical chromosome aberrations. This aberrant karyotype was correlated with increased FDG uptake. Three of five meningiomas with monosomy 1p were classified as grade II according to WHO, while only one of 20 tumors without monosomy 1p was classified as grade II. Thus, monosomy 1p and elevated FDG uptake in PET are to be regarded as cytogenetic and metabolic parameters for the aggressiveness of meningiomas. PMID- 7889509 TI - An isochromosome of the long arm of chromosome 18 in a patient with myelodysplastic syndrome with myelofibrosis. AB - A case of myelodysplastic syndrome (MDS) with myelofibrosis and i(18q) is reported. The patient, a 29-year-old Chinese man, was noted to be anemic over a 10-year period. Recently, his spleen became progressively massive and bone marrow aspirates yielded "dry taps" on several occasions. Hematologic investigation disclosed pancytopenia, numerous nucleated red cells, and slightly increased myeloblasts (8%) in the peripheral blood. Bone marrow aspirate and biopsy revealed hypercellular marrow, trilineage dysplasia, and significant reticulin fibrosis, but without collagen formation. Bone marrow karyotypic analysis with R banding showed an isochromosome 18q as a sole abnormality in 20 of 24 metaphases analysed. The patient died of severe anemia and bleeding due to bone marrow failure. We believe that i(18q) and myelofibrosis may be related to his poor prognosis. PMID- 7889511 TI - Tetraploidization and progressive loss of 6q in a squamous cell carcinoma of the parotid gland. AB - Cytogenetic analysis of short-term cultures from a squamous cell carcinoma (SCC) of the parotid gland revealed one clone with loss of the Y chromosome only, as well as three related subclones: 91,XXYY,add(6)(q21), 11,t(11;22)(q13;q11),ins(15;?)(q22;?)[cp5+ ++]/91,XXYY,add (6)(q21), 11,add(11)(p11), ins(15;?)(q22;?),der(22)t(11;22)(p11;q11)[2]/91,XXYY,add(6)(q11), 11,add(11)(p11),ins(15;?)(q22;?),der(22) t(11;22)(p11;q11) [cp4]. The finding of only one copy of all structurally rearranged chromosomes in a near-tetraploid karyotype indicates that tetraploidization was an early event in tumorigenesis. Rearrangements, in particular deletions, of 6q have previously been associated with adenoid salivary gland malignancies. Our finding of progressive 6q loss with clonal evolution, combined with the fact that 6q deletions were also seen in the two previously reported SCCs of the salivary glands, indicate that loss of genetic information from this chromosome arm is characteristic for most types of salivary gland carcinomas, irrespective of their histologic differentiation. PMID- 7889513 TI - Chromosomal changes in renal oncocytomas. Evidence that t(5;11)(q35;q13) may characterize a second subgroup of oncocytomas. AB - Many of the reported oncocytomas have different chromosome abnormalities, indicating that they comprise a cytogenetically heterogenous group of tumors consisting of potentially cytogenetic subgroups. We have performed cytogenetic studies on nine renal oncocytomas. Clonal abnormalities were present in eight tumors. The findings most observed were the loss of the Y chromosome, and abnormalities of chromosomes 1 and 22. We also observed telomeric associations (tas) in two tumors and structural aberrations of chromosomes 9p and 19q, as well as monosomy 10. In two cases we found a similar reciprocal t(5;11)(q35;q13) in two cases. Review of the literature disclosed one other oncocytoma with a t(5;11) (q35;q13). This suggests that t(5;11)(q35;q13) defines a (second) subset of oncocytomas apart from the subgroup specifically associated with the loss of chromosomes 1 and Y. PMID- 7889512 TI - Cytogenetic changes in ovarian mucinous cystadenocarcinoma of low malignant potential with persistent pseudomyxoma peritonei. AB - Minimal cytogenetic data are available for low malignant potential ovarian neoplasms, and none for those complicated by pseudomyxoma peritonei. Cytogenetic analysis was performed on tissue obtained from a patient undergoing repeat evacuation of mucin and mucin-producing implants in pseudomyxoma peritonei originating from an ovarian mucinous cystadenocarcinoma of low malignant potential. Specimens obtained from intraperitoneal implants during one of the cyto/mucin-reductive procedures revealed a mixture of normal female karyotype (46,XX) and an abnormal karyotype with a deletion involving the short arm of chromosome 1, and a balanced translocation involving chromosomes 2 and 6, [46,XXdel(1)(p21p31), t(2;6)(q35;p21)]. The vast majority of the cells from three subsequent cyto/mucin-reductive procedures displayed a normal female karyotype with few cells containing random abnormalities. PMID- 7889514 TI - Double-minute chromosomes appearing in a patient with myelodysplastic syndrome with disease evolution. AB - We present the first case of a myelodysplastic syndrome (MDS) demonstrating an association between the appearance of double-minute chromosomes (dmin) and disease progression. This 59-year-old Japanese woman showed a deletion of the long arm of chromosome 5 [del(5)(q21q34)] and monosomy 9, when she was diagnosed as having refractory anemia with an excess of blasts (RAEB). Subsequential cytogenetic analyses demonstrated that the neoplastic cells in the peripheral blood had six copies of dmin, when the disease progressed into RAEB in transformation (RAEBt). This cytogenetic change was consistently observed when the patient developed the leukemia phase. The findings in this case suggest that the appearance of dmin may be linked to progression of the disease. PMID- 7889516 TI - Translocation (1;14)(p34;q11) and trisomy 8 in a T-cell acute lymphoblastic leukemia patient. AB - A case of T-cell acute lymphoblastic leukemia (T-ALL) in a 25-year-old man cytogenetically characterized by a t(1;14)(p34;q11) and trisomy 8 is reported. These chromosome abnormalities were observed in 82% of the analyzed metaphases. Fluorescence in situ hybridization (FISH) with a probe for the centromere of chromosome 8 was used to correlate cellular morphology in bone marrow (BM) cells with May-Grunwald-Giemsa smears and the cytogenetic alterations. By FISH analysis, trisomy 8 (and presumably the associated t[1;14]) was demonstrated only in lymphoid blast cells but not in the rest of the cells belonging to other hematopoietic lineages. PMID- 7889515 TI - Involvement of chromosome 22 in ependymomas. AB - We have karyotyped a total of twelve ependymomas using GTG-banding including seven for which preliminary results have already been published. One case showing hyperdiploid main line with two marker chromosomes was further analyzed by nonisotopic chromosome in situ suppression hybridization. It was shown that the marker chromosomes consisted of 1q, 14q and 1q, and 22q. The possible role of chromosome 22 in ependymomas and the usefulness of fluorescence in situ hybridization for cytogenetic analysis in tumor investigation are discussed. PMID- 7889517 TI - Cytogenetic and FISH investigations on tetrasomy 8 in ANLL. AB - Two patients with "de novo" ANLL and tetrasomy of chromosome 8 at diagnosis are described. A mosaic karyotype with coexistence of normal metaphases was found in both cases. Trisomy 8 was also present in one metaphase of the first patient. Fluorescent in situ hybridization with a centromeric probe from chromosome 8 was applied in the second case, confirming the presence of a minor population with trisomy 8 in interphase nuclei. PMID- 7889518 TI - Is trisomy 4 a secondary chromosomal abnormality in acute myeloblastic leukemia? AB - Cytogenetic studies were carried out in a patient with acute monocytic leukemia (AML-M5) at diagnosis and in relapse. While no chromosome abnormality was detected initially, isolated trisomy 4 was found in relapse. The primary or secondary nature of trisomy 4 as the sole abnormality in AML is discussed. PMID- 7889520 TI - Trisomy 20 characterizes a second group of desmoid tumors. PMID- 7889519 TI - Translocation(11;19)(q14-21;p12) in a parotid mucoepidermoid carcinoma of a child. PMID- 7889521 TI - Interphase cytogenetics of the t(8;21)(q22;q22) associated with acute myelogenous leukemia by two-color fluorescence in situ hybridization. AB - In the translocation (8;21)(q22;q22) associated with acute myelogenous leukemia (AML), part of the long arm of chromosome 8 is reciprocally translocated onto chromosome 21. At the molecular level the translocation results in the fusion of the 5' region of the AML1 gene on chromosome 21 and almost the entire CDR gene (also ETO or MTG8) on chromosome 8. The translocation can be demonstrated by techniques such as Southern blot analysis of DNA and reverse transcription polymerase chain reaction (RT-PCR) analysis of mRNA. Neither of these methods demonstrates the translocation in individual cells. To detect the translocation at the single cell level, we used two probes, a cosmid clone containing the first five exons of AML1 and a P1 clone containing the entire CDR gene. Hybridization of the two probes to the distal and proximal side of the translocation breakpoint on chromosome 8 was expected to highlight the 8q-derivative in an interphase cell. To demonstrate the ability to identify the translocation in interphase cells using two-color FISH, these two probes were hybridized simultaneously to the Kasumi-1 cell line containing the 8;21 translocation and to t(8;21)-positive leukemic cells from a patient. Each probe was detected with a different color so that their relationship in the sample could be determined within the same interphase cell. Simultaneous hybridization of the CDR and AML1 probes to interphase cells resulted in one red and one green hybridization signal randomly located in the cell, from the hybridization to the normal chromosomes (8, 21), and one red-green pair of signals from the close hybridization of the two probes to the fusion gene on the derivative 8q-chromosome, indicating the translocation. This technique may be a useful complement for the analysis of the t(8;21), since critical information can be obtained from samples not suited for RT-PCR and conventional cytogenetic techniques. In addition, it may be useful for the assessment of minimal residual disease where RT-PCR is of limited value. PMID- 7889523 TI - Inhibition of epidermal growth factor binding system by ionizing radiation in A431 human squamous carcinoma cells. AB - To elucidate the effect of ionizing radiation on the membrane anchored signal transduction, the binding of 125I epidermal growth factor (EGF) to its receptor (EGF-R) and the EGF-dependent EGF-R tyrosine phosphorylation were examined in a human squamous cell carcinoma cell line, A431. The significant suppression of 125I EGF binding to A431 cells was observed from 3-5 h after 10 Gy irradiation, whereas this inhibition was not observed both in non-irradiated and in 5 Gy irradiated cells. This phenomenon was mediated by the protein kinase C pathway, because the inhibition was not observed in cells which had been pretreated with phorbol ester and treated with an inhibitor of the enzyme, H7. Scatchard analysis showed that the receptor affinity was decreased. In contrast, the level of EGF dependent EGF-R-tyrosine phosphorylation was not decreased, compared with non irradiated cells. These results suggest that ionizing radiation may modulate the function of EGF/EGF-R interaction through the direct activation of protein kinase C. PMID- 7889522 TI - Effect of membrane free fatty acid alterations on the adhesion of human colorectal carcinoma cells to liver macrophages and extracellular matrix proteins. AB - Epidemiologic studies have linked diets high in animal fat with colon carcinogenesis. A number of animal tumor models have shown that diets rich in omega-3 fatty acids inhibit colon carcinogenesis while diets rich in omega-6 fatty acids promote tumor growth. This study examines whether modification of the membrane fatty acid composition of both moderately (CX-1) and poorly differentiated (MIP-101 and Clone A) human colorectal carcinoma cells alters their interaction with Kupffer cells and extracellular matrix proteins (collagen type IV, fibronectin and laminin). The cells were treated with 15-16 micrograms/ml of docosahexanoic acid (22:6, omega 3) or linoleic acid (18:2,omega 6). Gas chromatography showed significant alterations in the membrane fatty acid composition of the human colorectal cancer cell lines. Binding assays were performed by measuring adherence of 51Cr-labelled tumor cells to Kupffer cell monolayers or to immobilized proteins. Omega-3 treatment significantly decreased the Kupffer cell binding of only the CX-1 line while omega-6 treatment decreased binding of all three cell lines. In contrast both omega-3 and omega-6 treatment of MIP-101 cells decreased binding to the extracellular matrix proteins with the omega-6 effect being more pronounced. These results indicate that the binding characteristics of the colon cancer cells to both Kupffer cells and extracellular matrix proteins may be determined in part by the membrane fatty acid composition. Decreased adherence to extracellular matrix proteins may lead to increased cell motility and invasiveness. Since Kupffer cell binding precedes tumor cell phagocytosis and killing, decreased binding may improve tumor cell survival. PMID- 7889524 TI - Enhanced effect of epidermal growth factor on pulmonary metastasis and in vitro invasion of rat mammary carcinoma cells. AB - We examined the effects of epidermal growth factor (EGF) on metastatic and in vitro invasive capacity of weakly malignant ER-1 cells derived from a rat mammary carcinoma cell line, c-SST-2. EGF enhanced the metastatic capacity and in vitro invasiveness to reconstituted basement membrane, Matrigel, of ER-1 cells in a dose-dependent fashion. EGF-stimulated invasiveness was inhibited by anti-EGF antibody, which is able to neutralize the binding of EGF to EGF receptor, in the invasion assay system. EGF stimulated chemotactic migration toward fibronectin, laminin or newborn rat fibroblast-conditioned medium which was used as a chemoattractant in the in vitro invasion assay, but showed neither adhesion to Matrigel nor production of gelatinase and plasminogen activators. These results suggested that the increased metastatic and invasive capacity of ER-1 cells by EGF might be due to the increase in cell motility. PMID- 7889525 TI - Extremely high production of thymidine by TNF-susceptible L929 cells. AB - We confirmed with the use of crystal violet bioassay the high susceptibility of mouse L929 cells to the cytotoxic action of recombinant tumor necrosis factor alpha (TNF). However, when a [3H]thymidine release assay was used for the same purpose, we found that [3H]thymidine uptake by the L929 cells, in contrast to low malignant TNF-resistant spontaneously transformed Syrian hamster embryo cells of the STHE strain, was significantly reduced (P < 0.001). To investigate the mechanism of the low incorporation of [3H]thymidine in L929 cells the culture media from intact L929 cells was used for competition experiments with [3H]thymidine incorporation in the STHE target cells. The undiluted supernatant from L929 cells significantly (up to 83-97%) reduced [3H]thymidine uptake by the STHE cells. Fifty percent inhibition of [3H]thymidine uptake was achieved at L929 supernatant dilutions up to 1:8 (in 4 h incubation), up to 1:16 (in 20-42 h incubation) and even up to 1:32 (in 42 h incubation). The same high level of inhibition of [3H]thymidine uptake by STHE cells was seen with a commercial specimen of a thymidine (Sigma) at a concentration near 500 ng/ml. Thus, we conclude that a resistance of L929 cells to [3H]thymidine uptake is related to their unusually high production of cold thymidine. PMID- 7889526 TI - Detection of Epstein-Barr virus and human papillomavirus in nasopharyngeal carcinoma by the polymerase chain reaction technique. AB - We used the PCR technique to detect the Epstein-Barr virus (EBV) and human papillomavirus (HPV) DNA in paraffin-embedded tissues from Greek patients with nasopharyngeal carcinoma (NPC). The oligonucleotide primers used for the detection of EBV amplify a 375-bp long sequence from the EcoRI B fragment of the viral genome, whereas for HPV the primers amplify a 151-bp long sequence of the viral genome. The PCR products were analysed by agarose gel electrophoresis and visualised by UV illumination after staining with ethidium bromide. Sixty-three specimens were examined. EBV specific sequence was amplified in 20 (32%) and HPV in 12 (19%) out of the 63 samples. There was no co-infection with EBV and HPV. Although there is a high correlation of EBV infection with poorly differentiated NPC in patients from Southern China and South-East Asia, the restricted distribution suggests genetic or environmental cofactors in the development of the neoplasm. Our results confirm this suggestion since there was only a 32% correlation of EBV with NPC in Greece. HPV may also be involved in the carcinogenesis of EBV-negative squamous cell nasopharyngeal carcinomas. PMID- 7889527 TI - Induction of apoptotic cell DNA fragmentation in human cells after treatment with hyperthermia. AB - The biological significance of apoptosis is becoming increasingly clear. Its relevance in tumor response to treatment as well as recent evidence for its important function as a regulating mechanism in tumorigenesis has also been demonstrated. One of the most prominent biological features of apoptosis is nucleosomal DNA fragmentation. In this communication, we present a study of DNA fragmentation in Raji cells which have been subjected to hyperthermia treatment to induce apoptosis. We found that the induction and onset of fragmentation is swift, and consistent with previous reports that fragmentation must be a rapid event. PMID- 7889529 TI - Human calgizzarin; one colorectal cancer-related gene selected by a large scale random cDNA sequencing and northern blot analysis. AB - A cDNA library was constructed from COLO 205 and 1056 clones randomly selected from this library were partially sequenced. Two hundred and two (38.4%) out of 526 independent genes had more than 80% similarity to the genes reported in GenBank. In Northern blot analysis, 96 out of 98 genes were shown to be expressed at the same level in colon and lung carcinoma cell lines and control fibroblasts. Only two clones, including human synovial phospholipase A-2 and a homologue to rabbit calgizzarin, were expressed at different levels among these cell lines. The full sequence of human calgizzarin was determined and its expression was remarkably elevated in colorectal cancers compared with that in normal colorectal mucosa. PMID- 7889528 TI - beta-Endorphin expression in gross cystic breast disease. AB - Opioid peptides have a variety of pathophysiologic actions, playing a novel important role in human breast cancer. The expression of beta-endorphin was studied in 84 human breast cyst fluids from gross cystic breast disease-affected patients. The concentration of beta-endorphin in pooled breast cyst fluids was over four-fold higher than in respective plasma with a significant increase in the mean value of the 'metabolically active' apocrine cysts when compared with flattened cysts (P < 0.001). The higher levels of Type I cyst suggest de novo mammary synthesis of endogenous opioid peptides and could represent an altered expression of biosynthetic activity of apocrine breast cells, providing a possible explanation on functional changes of gross cysts, on the mechanism of their formation and a perspective relationship to breast cancer risk. PMID- 7889530 TI - Mechanistic study of the inhibition of aflatoxin b1-induced hepatotoxicity by dimethyl 4,4'-dimethoxy-5,6,5',6'-dimethylenedioxy biphenyl-2, 2'-dicarboxylate. AB - The mechanism of DDB (dimethyl 4,4'-dimethoxy-5,6,5',6'-dimethylenedioxy biphenyl 2,2'-dicarboxylate) prevention of aflatoxin B1 (AFB1)-induced hepatotoxicity in rats has been investigated. Pretreatment of DDB (200 mg/kg) daily for 4 days significantly suppressed (P < 0.05) the AFB1-induced hepatic damage as evidenced by the increase of serum marker enzymes. DDB induced rat hepatic cytochrome P450IA1, IIB1 and glutathione S-transferase activities. The hepatic microsomes derived from DDB treated rats increased the mutation frequency of AFB1 and enhanced the binding of AFB1 to DNA. However, the hepatic S9 fraction from DDB treated rats showed a protective effect against AFB1-induced damage. It is concluded that the protective effect of DDB against AFB1-induced damage might be mediated by the induced glutathione S-transferase activity and not from the accelerated hepatic cytochrome P450 detoxification pathway of AFB1 which was previously believed. PMID- 7889531 TI - Expression of activins and activin receptors in human retinoblastoma cell line Y 79. AB - Activin is a member of TGF beta family and is known to inhibit neuronal differentiation in certain tumor cell lines. In this study, the messenger RNA expression of activin subunits and activin receptors was characterized in retinoblastoma cell line Y-79 using the reverse transcription-polymerase chain reaction as well as in situ hybridization. The identity of the RT-PCR products was confirmed by DNA sequencing of PCR products. The activin protein production was determined by immunocytochemistry. We found that Y-79 cells transcribe mRNAs coding activin subunits and activin receptors and produce activin proteins. Our results imply that activin may have autocrine functions in these cells. PMID- 7889532 TI - Identification and partial sequence of a cDNA that is differentially expressed in human brain tumors. AB - Differential display technique was used to identify mRNAs that are differentially expressed in malignant versus benign brain tumors. Using this method, a novel 1.4 kb long cDNA (MM1) clone was isolated and sequenced. The nucleotide and the translated amino acid sequence of MM1 cDNA clone did not show significant homology to any known sequence in the Genebank. The expression of MM1 appears to be almost eightfold higher in glioblastomas compared to low grade astrocytomas and slightly higher in malignant meningiomas than in benign meningiomas. The size of mRNA from northern analysis appears to be 7 kb, which is much higher than the size of the isolated MM1 cDNA clone. Expression of MM1 was also seen in various cell lines derived from human tumors including glioblastomas. Whereas low level expression was seen in kidney, esophagus, liver, lymph node, ovary and testis, none of the other tissues from a total of 18 different human organs showed any MM1 expression. PMID- 7889533 TI - Analysis of MTS1/CDK4 in female breast carcinomas. AB - Multiple factors, both environmental and genetic, are thought to play roles in breast carcinogenesis. The recently cloned multiple tumor suppressor gene (MTS1), the product of which interacts with CDK4 to regulate cell growth, has been found to be mutated with high frequency in a variety of cell lines as well as primary tumors of different histologic types. Using PCR-SSCP, we analyzed exons one (126 bp) and two (307 bp) of the MTS1 gene to determine the incidence of mutation in a population of 50 primary breast adenocarcinomas and corresponding normal tissue. Analysis of five breast tumor cell lines was also performed. We found no mutations in the MTS1 gene in the primary breast tumor samples. One cell line was found to have a homozygous deletion of the gene. Our results suggest that the MTS1 gene is not mutated with increased frequency in primary breast tumors, and thus may not play a major role in breast carcinogenesis. PMID- 7889534 TI - Tumor targeting with monoclonal antibodies. Advances in the Applications of Monoclonal Antibodies in Clinical Oncology, symposium. Porto Carras, Halkidiki, Greece, May 4-6, 1992. PMID- 7889535 TI - Antitumor effects of an antibody-carboxypeptidase G2 conjugate in combination with a benzoic acid mustard prodrug. AB - The F(ab')2 fragment of the antitumor monoclonal antibody, A5B7, was covalently linked to the bacterial enzyme carboxypeptidase G2 (CPG2). The resulting conjugate was used in combination with a prodrug of a benzoic acid mustard alkylating agent to treat human colon tumor xenografts in a two-step targeting strategy, antibody-directed enzyme prodrug therapy (ADEPT). The prodrug, 4-[(2 chloroethyl) (2-mesyloxyethyl)amino]-benzoyl-L-glutamic acid is rapidly converted by CPG2 to a drug that is at least 15x more toxic in vitro against LS174T colorectal tumor cells than the prodrug. Optimal tumor/blood ratios of the A5B7 CPG2 were achieved 72 h after administration of the conjugate to athymic mice bearing established LS174T tumor xenografts. Significant antitumor activity was seen in LS174T tumor-bearing mice treated with the conjugate followed 3 d later by the prodrug. In contrast, prodrug, conjugate, or active drug alone did not result in any antitumor activity in this tumor model. These studies demonstrate the advantage of a two-step ADEPT system for the treatment of colorectal cancer. PMID- 7889536 TI - pS2--a new cytosolic protein recognized by monoclonal antibodies as a marker of hormone sensitivity in breast cancer. AB - Using a new immunoradiometric assay (ELSA pS2 Cis-France), a total of 200 cytosols obtained from primary breast tumors were examined for pS2 content, which is an estrogen-regulated protein actually studied as a marker of hormone sensitivity and favorable prognostic factor in breast cancer. In our patient group, the median pS2 value corresponding to 5.3 ng/mg of cytosolic proteins was used as cutoff. pS2 content was not related to menopause status, tumor size, or nodal involvement, whereas a positive correlation was found between pS2 and ER/PgR status. Moreover, the association of pS2 with steroid receptors seems to identify subgroups of patients better than ER/PgR alone. PMID- 7889537 TI - Targeting of superantigens. AB - The bacterial superantigen staphylococcal enterotoxin A (SEA) is an extremely potent activator of T lymphocytes when presented on MHC class II antigens. In order to induce T lymphocytes to reject a tumor, we substituted the specificity of SEA for MHC class II molecules with specificity for tumor cells by combining SEA with a MAb recognizing colon carcinomas. Chemical conjugates or recombinant fusion proteins of the MAb C215 and SEA retained excellent antigen binding properties whereas the binding to MHC class II was markedly reduced. The hybrid proteins directed SEA responsive T cells to tumors with specificity determined by the specificity of the MAb. Significant tumor cell killing was obtained at picomolar concentrations of the hybrid proteins and was the result of direct cell mediated by cytotoxicity as well as production of tumoricidal cytokines by T cells. Targeting of superantigens represents a novel approach to specific immunomodulation and deserves further study as a potential therapy for malignant disease. PMID- 7889538 TI - Monoclonal antibodies for the treatment of metastases. Evaluation of strategies using a syngeneic rat model. AB - To investigate critical factors influencing the localization and antitumor effects of monoclonal antibodies (MAb) or toxic conjugates, we have adapted a single rat sarcoma, HSN, for preferential growth in the lungs, liver, and lymph nodes (the major sites of metastasis in humans) and have raised a panel of syngeneic rat MAbs to a stably-expressed cell surface antigen. Using this model we have shown that localization in tumors is significantly influenced by their anatomical location and vascularization, and the degree of MAb interaction with host cells. Uptake in small hepatic tumors was excellent, but access to lung tumors was limited by the poor permeability of pulmonary vessels. HSN cells transfected with th human IL-2 gene and coinjected in low numbers with parental tumors secreted sufficient cytokine to enhance the local permeability of vessels and doubled MAb localization in tumors without any systemic toxicity, suggesting that regional delivery of IL-2 may be used to enhance MAb localization in this situation. In order to extent the applicability of the model to studies of MAbs raised against human tumor targets, we have transfected the human c-erb B-2 gene (homolog of the rat neu) into the highly metastatic HSN.LV subline. MAbs raised against the external domain of the p185 product can now be screened for their ability to localize in metastases, and for various conjugates to inhibit tumor growth either independently of, or in association with, a fully functional immune system. PMID- 7889540 TI - A universal antibody-derived targeting agent. AB - We report bacterial expression of a single-chain antibody (ScFv) reactive against the haptens 4-hydroxy-3 nitrophenylacetic acid (NP) and 4-hydroxy-3-iodo-5 nitrophenylacetic acid (NIP) that is suitable for targeting to mammalian cells in vitro in a novel two-step targeting strategy. Hapten-derivatized primary antibodies of known specificity, bound to target cells, can capture the ScFv. Specificity resides in the interaction of the primary targeting antibody with the target and the interaction of the ScFv for NP/NIP, since the ScFv does not bind cells and nonderivatized antibodies bound at cells cannot capture the ScFv. The ScFv described here can therefore be considered as a universal agent for delivery of drugs, toxins, or radionuclides to any cell type for which a previously characterized antibody exists. PMID- 7889539 TI - Antigen recognition and targeted delivery by the single-chain Fv. AB - The single-chain Fv (sFv) has proven attractive for immuno-targeting, both alone and as a targeting element within sFv fusion proteins. This chapter summarizes the features of sFv proteins that have sparked this interest, starting with the conservation of Fv architecture that makes general sFv design practical. The length and composition of linkers used to bridge V domains are discussed based on the sFv literature; special emphasis is given to the (Gly4Ser)3 15-residue linker that has proven of broad utility for constructing Fv regions of antibodies and other members of the immunoglobulin superfamily. The refolding properties of sFv proteins are summarized and examples given from our laboratory. Spontaneous refolding from the fully reduced and denatured state, typified by 26-10 sFv, is contrasted with disulfide-restricted refolding, exemplified by MOPC 315 and R11D10 sFv proteins, which recover antigen binding only if their disulfides have been oxidized prior to removal of denaturant. The medical value of sFv proteins hinges on their reliability in antigen recognition and rapidity in targeted delivery. Detailed analysis of specificity and affinity of antigen binding by the 26-10 antidigoxin sFv has demonstrated very high fidelity to the binding properties of the parent 26-10 sFv. These results gave confidence to the pursuit of more complex biomedical applications of these proteins, which is indicated by our work with the R11D10 sFv for the imaging of myocardial infarctions. Diagnostic imaging and therapeutic immunotargeting by sFv present significant opportunities, particularly as a result of their pharmacokinetic properties. Intravenously administered sFv offers much faster clearance than conventional Fab fragments or intact immunoglobulin with minimal background binding. PMID- 7889541 TI - Monoclonal antibodies for intravesical radioimmunotherapy of human bladder cancer. AB - Local administration of radioimmunoconjugates may allow successful tumor therapy. Bladder cancer appears well suited to this approach, because of its superficial and multifocal nature, and because it will allow direct intravesical administration of conjugates. Implantation of human bladder cancer cell lines in the bladder wall of nude rats results in tumor formation, providing an excellent model to test this. We have developed two murine monoclonal antibodies (MAbs), BLCA-8, IgG3, and BLCA-38, IgG1, both of which react with malignant cells and shed into voided urine of patients with transitional cell carcinoma (TCC) of the bladder, but not with normal bladder urothelial cells. Radioimmunoconjugates produced with 131Iodine (131I) or 125I have been used for biodistribution studies following administration directly into the bladder. Radioiodinated intact MAbs or Fabs administered intravesically into nontumor-bearing rats did not leak into the systemic circulation and were stable in urine for up to 100 h. Biodistribution studies carried out following intraperitoneal or intravesical administration of radioimmunoconjugates to tumor-bearing nude rats indicate good tumor uptake of both MAbs. Together with immunoreactivity assays, these studies demonstrate that 131I-labeled MAbs have considerable potential for intravesical radioimmunotherapy of human bladder tumors, and further studies are under way. PMID- 7889542 TI - Technetium-99m-labeled antibodies. Stability compared to 125I labeled antibodies. AB - It is essential in any method for radiolabeling antibody with 99mTc that the labeling procedure is rapid and reliable, producing a highly stable 99mTc antibody complex with minimal effect on the immunoreactivity of the antibody. In the present study, analysis of the stability and homogeneity of radiolabeled (99mTc and 125I) antibodies (HMFG1 and PR1A3) was carried out by fast protein liquid chromatography (FPLC) using superose-6 and S-200 columns, and by polyacrylamide gel electrophoresis (PAGE) followed by autoradiography. Superose 6 and S-200 gel filtration analysis showed the radiolabel (99mTc or 125I) eluting with a retention time identical to that of native antibody. No peaks of relative molecular size (Mr) corresponding to possible antibody fragments were seen in either the UV or the radioactive FPLC elution profiles. PAGE analysis of 99mTc labeled antibody, however, revealed the presence of a number of radiolabeled antibody fragments (Mr < IgG) that were not detected by the same analysis of 125I labeled antibody. The stability of the radiolabeled antibodies in serum in vitro was also studied. FPLC (superose-6) analysis after 45 h incubation in normal serum in vitro revealed 3.3% (HMFG1), and 20% (PR1A3) of the 99mTc on a molecule or aggregate with a Mr greater than that of IgG. There is also the appearance of small amounts of 99mTc-labeled material with a Mr < IgG in the later fractions (2.2% for HMFG1 and 4.9% for PR1A3). Similar results were obtained using radioiodinated antibody, although the small amount of low molecular size material detected as a single peak with a longer retention time than the 99mTc equivalent corresponds to free iodide. PMID- 7889543 TI - A recombinant single-chain antibody interleukin-2 fusion protein. AB - Recombinant interleukin-2 (rIL-2) therapy has been shown to be of value in the treatment of some cases of melanoma and renal cell carcinoma. However, its use can be limited by severe systemic toxicity. Targeting rIL-2 to the tumor should improve the antitumor immune response and decrease the systemic toxicity. With this aim, we have employed recombinant DNA techniques to construct a single-chain antibody interleukin-2 fusion protein (SCA-IL-2). The protein used in this model system consists of the variable domains of the antilysozyme antibody D1.3 fused to human IL-2 and is expressed in E. coli. It retains antigen-binding specificity and has the full biological activity of rIL-2. This approach can be taken to generate SCA-IL-2 proteins that bind to appropriate cellular antigens. In vivo administration of tumor-binding SCA-IL-2 should result in a localized high concentration of rIL-2 in the tumor tissues, maximizing the anti-tumor response while keeping systemic side effects to a minimum. PMID- 7889545 TI - Identification of prodrug, active drug, and metabolites in an ADEPT clinical study. AB - Antibody-directed enzyme prodrug therapy (ADEPT) involves two phases. The first is an antibody-enzyme conjugate that localizes to tumor. The second phase is a prodrug that is administered when the enzyme-conjugate has cleared from blood and other nontumor tissues. In the pilot-scale clinical trial, the prodrug has been measured--in the plasma of patients, by liquid chromatography (HPLC) and by liquid chromatography-mass spectrometry (LC-MS). Active drug has been detected and metabolites identified. An indirect measurement of enzyme-conjugate in the plasma of patients has also been developed. PMID- 7889544 TI - Membrane-bound and soluble IL-2 receptors (p55 and p75 chains) on peripheral blood mononuclear cells from patients with solid malignancies. AB - The aim of the investigation was to study directly the IL-2 receptor (IL-2R) and its subunits, p55 and p75 chains, either membrane-bound or soluble, on PBMC of patients with solid malignancies and, indirectly, the same patients' PBMC ability to produce IL-2. Fifty-eight cancer patients, 29 men and 29 women, were studied: their mean age was 57.3 yr, range 35-79. Twenty-two healthy age-sex-matched subjects served as controls. The tumors were the most common and the most representative among human cancers, i.e., breast, lung, head and neck, digestive tract and liver, prostate and gynecologic cancers: they were generally in advanced stages and in 23 cases metastatic. The PBMC proliferative response to PHA, PHA plus IL-2, and IL-2 was evaluated along with the response to PHA in the presence of anti-p55, anti-p75 monoclonal antibodies, or both. Moreover, membrane bound IL-2R (p55 and p75 chains) on PHA-stimulated PBMC was detected, along with soluble IL-2R in the serum and in the culture supernatants. The conclusions suggest that in solid malignancies: the membrane-bound IL-2Rs, both p55 and p75 chains, are expressed normally, there is an high serum level of soluble IL-2R, there is a normal release of soluble IL-2R in culture, and there is an indirect evidence of a lack of IL-2 production. Therefore, no primary impairment of IL-2R was found in solid tumors. Moreover, in our study we have found no difference in any parameter studied between patients with and patients without metastases. PMID- 7889546 TI - Volumetric intracoronary ultrasound: methods and validation. AB - Intracoronary ultrasound (ICUS) not only allows visualization of the vessel lumen, it gives a unique view of the transmural components of the artery wall. Analysis of lumen and plaque volume is necessary for studying atherosclerotic disease progression or regression and the mechanisms of therapeutic coronary interventions. A real-time, ICUS pull-back data acquisition scheme was developed to acquire calibrated, cardiac-gated volumetric image data sets. A semiautomated border detection scheme was implemented using dynamic programming. In phantoms, estimated area profiles were very reproducible as measured by the root-mean square from the mean (3.8-5.9%). In phantom volume estimates, improved reproducibility (standard deviation = 1.2-3.6%) was obtained as positive and negative errors in area profiles were averaged out. Phantom volumes were also accurate when compared to true water displacement volume. The mean error ranged from -2.59 to -8.94%. When compared to quantitative single and biplane angiographic analysis, ICUS volumetric estimates tended to be superior to single plane analysis (error -5.06 +/- 2.48% vs -9.96 +/- 8.01%), but similar to optimal biplane analysis (error -5.06 +/- 2.48% vs -6.34 +/- 3.08%). In vivo reproducibility was assessed by performing multiple cardiac-gated pull-backs through experimentally induced stenosis. Over the length of the stenosis, excellent reproducibility of area profiles (+/- 5.9%) and volumes (+/- 1.9%) was obtained for cardiac-gated acquisitions. We conclude that volumetric ICUS provides accurate and reproducible estimates of lumen volume. Thus this technique may be of use in clinical trials where changes lumen volumes and vessel area profiles are of interest. PMID- 7889547 TI - Effect of atrial septal occlusion on mitral area after Inoue balloon valvotomy. AB - The purpose of this study was to examine the influence of the atrial communication created during transseptal passage of the Inoue balloon catheter on calculated mitral valve area after balloon valvotomy for severe mitral stenosis. Even in the absence of oxymetric evidence for a shunt, atrial septal puncture may result in left-to-right shunting of blood with reported spurious increases in postvalvotomy mitral valve area calculations ranging from 16-29% in prior studies. Occlusion of the septal puncture site after double balloon valvotomy has previously been shown to result in decreased postvalvotomy mitral valve area determinations. We evaluated 20 patients undergoing mitral dilation. Each patient had three postvalvotomy measurements made: (1) with the Inoue balloon catheter positioned across the septum, (2) during septal occlusion with a 7F balloon-tip catheter, and (3) without any catheters across the septum. With the Inoue catheter across the septum after successful valvotomy, the cardiac output was 4.6 +/- 1.5 L/min and the calculated mitral valve area was 1.7 +/- 0.5 cm2. No difference was found in either cardiac output or valve area when the septum was unobstructed by catheters. During septal occlusion, however, the postvalvotomy cardiac output decreased to 4.3 +/- 1.3 L/min (P < 0.001) and the calculated mitral area decreased by 12% to 1.5 +/- 0.5 cm2 (P < 0.001). The calculated mitral valve areas determined with the Inoue catheter in place after valvotomy were in agreement with echo derived data. Although statistically significant differences in post-Inoue valvotomy cardiac output and calculated mitral valve area were found during septal occlusion, these differences were small.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889548 TI - What is the gold standard to measure mitral valve area postmitral balloon valvuloplasty? PMID- 7889549 TI - Directional atherectomy of left main stenoses. AB - Balloon angioplasty (PTCA) of left main (LM) stenoses is limited by frequent clinical restenosis. Directional coronary atherectomy (DCA) may be an effective alternative to PTCA due to its ability to achieve a greater postprocedural luminal diameter when treating bulky, eccentric plaques and aorto-ostial lesions. We analyzed the acute and long-term results following 24 DCA procedures in 22 patients with "protected" LM lesions. Acute success (residual stenosis < or = 40%, no major ischemic complications) was 88% overall, 100% in 13 planned procedures, and 73% in 11 adjunctive DCA procedures that followed suboptimal PTCA. Mean LM stenosis was reduced from 86% to 13% (P < 0.01). There were no procedural complications directly attributed to DCA. At a mean of 24 +/- 3 months, the clinical restenosis rate was 16%, survival was 100%, and event-free survival (freedom from death, MI, or repeat lesion-related interventions) was 89%. We conclude that DCA in protected LM lesions (1) can achieved excellent angiographic results with low procedural complication rates, (2) may succeed where PTCA yields suboptimal results, and (3) may provide late clinical outcomes superior to those of balloon angioplasty. PMID- 7889551 TI - All that glitters is not gold. PMID- 7889550 TI - Angioscopic evaluation of incompletely obstructing coronary intraluminal filling defects: comparison to angiography. AB - At 66 sites in 40 patients, we evaluated the sensitivity and specificity of coronary angiography in detecting intraluminal filling defects of varying sizes and in characterizing the contents (thrombus, intimal flap, both) of such defects using coronary angioscopy as "the gold standard." Overall angiographic sensitivity for thrombus was 37% and for intimal flap 45%. Specificity for thrombus was 100% and intimal flaps 96%. Angioscopically small flaps were less frequently seen angiographically (28%) than larger sizes (65%, p = 0.03). Angioscopically small thrombi were seen less often angiographically (30%) than larger ones (75%, p = 0.13). Filling defects (intimal flaps, thrombus, both) were characterized correctly in only 37% of sites. Angiography is relatively insensitivity in detecting intraluminal filling defects. Angioscopy may be preferred to or adjunctive with angiography in detecting these lesions. PMID- 7889552 TI - Retrograde nontransseptal balloon mitral valvuloplasty for rheumatic mitral stenosis. AB - Retrograde nontransseptal balloon mitral valvuloplasty is a relatively new technique for dilating stenosed mitral valves, wherein a specially designed steerable catheter is used to enter the left atrium retrogradely. Over a 1-yr period, 52 patients (34 M, 18 F; mean age 26.4 +/- 6.5 yr) with symptomatic noncalcific rheumatic mitral stenosis underwent balloon mitral valvuloplasty by this technique at our center. The procedure was completed in 51 out of the 52 patients and technically successful dilatation was achieved in 47 (90.4%) patients. The mean valve area increased from 0.8 +/- 0.2 cm2 to 1.86 +/- 0.37 cm2 and end diastolic gradients decreased from 21.2 +/- 9.4 mm Hg to 4.0 +/- 2.2 mm Hg. Significant mitral regurgitation (> 2+) developed in two (3.9%) patients, and both remained stable on medical treatment. In two patients, there was a significant decrease in femoral pulse, which improved with thrombolytic therapy. Our study is the first report of this technique from a center other than that of its origin. The results of this study further establish that this new retrograde technique may be a useful alternative to the conventional transseptal techniques for mitral valvuloplasty. PMID- 7889553 TI - Acute coronary occlusion during early post-PTCA exercise testing: a rare but avoidable risk. AB - We describe here one instance of an acute occlusion of an angioplastied LAD coronary artery occurring during a treadmill stress test performed 2 d after the procedure. The occlusion occurred during the recovery period after a reasonably high level of stress was achieved without evidence of ischaemia. Similar instances described in the literature are summarized and discussed. In the light of these data, it might be prudent to avoid early post-PTCA exercise stress testing. PMID- 7889554 TI - Stress test early after coronary angioplasty: an old habit to be revived? PMID- 7889555 TI - Percutaneous double balloon valvotomy for bioprosthetic tricuspid stenosis. AB - We report two cases of percutaneous balloon valvotomy of porcine tricuspid valves and review the brief literature. Both procedures were successful, but "restenosis" resulted in tricuspid valve replacement in patient 2. The explanted valve showed leaflet thickening and calcified cuspal nodules. Patient 1 is improved 10 months later. PMID- 7889556 TI - International physiology. Development of left atrial thrombus following attempted percutaneous mitral valvuloplasty. AB - In this report, we describe two cases of attempted mitral valvuloplasty using an Inoue balloon in which left atrial thrombus was not present before transseptal puncture but developed within minutes of the puncture in one, and within 1 mo in the other, despite systemic anticoagulation. PMID- 7889557 TI - Part XII: Assessment of serial lesions in the proximal right coronary artery following intracoronary thrombolysis. AB - Assessment of angiographically serial coronary lesions at the time of diagnostic catheterization remains a difficult clinical problem. Doppler flow velocity data is easily obtainable and allows physiologic interrogation of the distal coronary microcirculation, but has limitations in the detection of some flow-limiting stenoses. In cases of serial lesions or distal arterial disease, particularly after thrombolysis, flow velocity data may be insufficient to identify the hemodynamic significance of the coronary lesions. Translesional pressure measurements may be combined with flow velocity data to support an appropriate physiologically based therapeutic approach. PMID- 7889558 TI - Right-to-left shunt following repair of partial anomalous pulmonary venous connection: a novel use of the Rashkind double-umbrella occlusion device. AB - A patient with partial anomalous pulmonary venous connection complicated by postoperative occlusion of the distal superior vena cava and a baffle leak causing right-to-left shunt is described. Surgery was avoided by balloon dilation and stenting of the superior vena cava. The baffle leak was closed with a Rashkind double-umbrella device. PMID- 7889559 TI - Imaginative use of umbrella device and stent together. PMID- 7889560 TI - Combined intraaortic balloon counterpulsation with synchronized coronary venous retroperfusion: the United States experience. AB - Prompted by severe cardiogenic shock, impending or manifest, three cases from the United States Retroperfusion Clinical Trials utilized intraaortic balloon counterpulsation combined with retroperfusion. Temporary stabilization and improvement was noted in all three cases and long-term survival was seen in two of the cases. The clinical and physiologic bases for combined use of these modalities is discussed. PMID- 7889561 TI - Use of half (disarticulated) Palmaz-Schatz stents for thrombus-containing coronary lesions. AB - Coronary stenoses associated with thrombus can lead to poor angioplasty results and increased procedural complications. Stenting in the presence of thrombus is associated with an increased risk of stent thrombosis. We report eight patients in whom half a Palmaz-Schatz stent was implanted for inadequate angioplasty results owing to thrombus. Stenting resulted in improved angioplasty results; no stent thrombosis occurred. PMID- 7889562 TI - The initiation of the limb bud: growth factors, Hox genes, and retinoids. PMID- 7889563 TI - Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage. PMID- 7889564 TI - Amyotrophic lateral sclerosis: recent insights from genetics and transgenic mice. PMID- 7889565 TI - Increased neutrophil respiratory burst in bcr-null mutants. AB - Philadelphia (Ph)-positive leukemias invariably contain a chromosomal translocation fusing BCR to ABL. The BCR-ABL protein is responsible for leukemogenesis. Here we show that exposure of bcr-null mutant mice to gram negative endotoxin led to severe septic shock and increased tissue injury by neutrophils. Neutrophils of bcr (-/-) mice showed a pronounced increase in reactive oxygen metabolite production upon activation and were more sensitive to priming stimuli. Activated (-/-) neutrophils displayed a 3-fold increased p21rac2 membrane translocation compared with (+/+) neutrophils. These results connect Bcr in vivo with the regulation of Rac-mediated superoxide production by the NADPH oxidase system of leukocytes and suggest a link between Bcr function and the cell type affected in Ph-positive leukemia. PMID- 7889566 TI - Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals. AB - The binding of erythropoietin (EPO) to its receptor (EPO-R) activates the protein tyrosine kinase JAK2. The mechanism of JAK2 inactivation has been unclear. We show that the hematopoietic protein tyrosine phosphatase SH-PTP1 (also called HCP and PTP1C) associates via its SH2 domains with the tyrosine-phosphorylated EPO-R. In vitro binding studies suggest that Y429 in the cytoplasmic domain of the EPO-R is the binding site for SH-PTP1. Mutant EPO-Rs lacking Y429 are unable to bind SH PTP1; cells expressing such mutants are hypersensitive to EPO and display prolonged EPO-induced autophosphorylation of JAK2. Our results suggest that activation of SH-PTP1 by binding to the EPO-R plays a major role in terminating proliferative signals. PMID- 7889567 TI - Fibroblast growth factors induce additional limb development from the flank of chick embryos. AB - Fibroblast growth factors (FGFs) act as signals in the developing limb and can maintain proliferation of limb bud mesenchyme cells. Remarkably, beads soaked in FGF-1, FGF-2, or FGF-4 and placed in the presumptive flank of chick embryos induce formation of ectopic limb buds, which can develop into complete limbs. The entire flank can produce additional limbs, but generally wings are formed anteriorly and legs posteriorly. FGF application activates Sonic hedgehog in cells with polarizing potential to make a discrete polarizing region. Hoxd-13 is also expressed in the ectopic bud, and an apical ectodermal ridge forms. A limb bud is thus established that can generate the appropriate signals to develop into a complete limb. The additional limbs have reversed polarity. This can be explained by the distribution of cells in the flank with potential polarizing activity. The results suggest that local production of an FGF may initiate limb development. PMID- 7889568 TI - Binding of pumilio to maternal hunchback mRNA is required for posterior patterning in Drosophila embryos. AB - Posterior patterning in Drosophila embryos is governed by nanos (nos), which acts by repressing the translation of maternal transcripts of the hunchback (hb) gene. Sites in hb mRNA that mediate this repression, named nanos response elements (NREs), have been identified. However, we know of no evidence of a direct interaction between nos, or any other protein, and the NRE. Here, we show that two proteins present in embryonic extracts, neither one nos, bind specifically to the NRE in vitro. Furthermore, we show that binding in vitro correlates with NRE function in vivo. One of the NRE-binding factors is encoded by pumilio (pum), a gene that, like nos, is essential for abdominal segmentation. These and other observations suggest that pum acts by recognizing the NRE and then recruiting nos. Presumably, the resulting complex inhibits some component of the translation machinery. PMID- 7889569 TI - Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. AB - Taking advantage of the restricted expression of metabotropic glutamate receptor subtype 6 (mGluR6) in retinal ON bipolar cells, we generated knockout mice lacking mGluR6 expression. The homozygous mutant mice showed a loss of ON responses but unchanged OFF responses to light. The mutant mice displayed no obvious changes in retinal cell organization nor in the projection of optic fibers to the brain. Furthermore, the mGluR6-deficient mice showed visual behavioral responses to light stimulation as examined by shuttle box avoidance behavior experiments using light exposure as a conditioned stimulus. The results demonstrate that mGluR6 is essential in synaptic transmission to the ON bipolar cell and that the OFF response provides an important means for transmitting visual information. PMID- 7889570 TI - Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. AB - The bHLH-ZIP protein Mad heterodimerizes with Max as a sequence-specific transcriptional repressor. Mad is rapidly induced upon differentiation, and the associated switch from Myc-Max to Mad-Max heterocomplexes seem to repress genes normally activated by Myc-Max. We have identified two related mammalian cDNAs that encode Mad-binding proteins. Both possess sequence homology with the yeast transcription repressor Sin3, including four conserved paired amphipathic helix (PAH) domains. mSin3A and mSin3B bind specifically to Mad and the related protein Mxi1. Mad-Max and mSin3 form ternary complexes in solution that specifically recognize the Mad-Max E box-binding site. Mad-mSin3 association requires PAH2 of mSin3A/mSin3B and the first 25 residues of Mad, which contains a putative amphipathic alpha-helical region. Point mutations in this region eliminate interaction with mSin3 proteins and block Mad transcriptional repression. We suggest that Mad-Max represses transcription by tethering mSin3 to DNA as corepressors and that a transcriptional repression mechanism is conserved from yeast to mammals. PMID- 7889571 TI - An amino-terminal domain of Mxi1 mediates anti-Myc oncogenic activity and interacts with a homolog of the yeast transcriptional repressor SIN3. AB - Documented interactions among members of the Myc superfamily support a yin-yang model for the regulation of Myc-responsive genes in which transactivation competent Myc-Max heterodimers are opposed by repressive Mxi1-Max or Mad-Max complexes. Analysis of mouse mxi1 has led to the identification of two mxi1 transcript forms possessing open reading frames that differ in their capacity to encode a short amino-terminal alpha-helical domain. The presence of this segment dramatically augments the suppressive potential of Mxi1 and allows for association with a mammalian protein that is structurally homologous to the yeast transcriptional repressor SIN3. These findings provide a mechanistic basis for the antagonistic actions of Mxi1 on Myc activity that appears to be mediated in part through the recruitment of a putative transcriptional repressor. PMID- 7889572 TI - Branch migration during homologous recombination: assembly of a RuvAB-Holliday junction complex in vitro. AB - The RuvA and RuvB proteins of E. coli promote the branch migration or movement of Holliday junctions during genetic recombination and DNA repair. Using small synthetic Holliday junctions in which the crossover point is confined near one end of the DNA molecule, we show that RuvAB-mediated branch migration occurs with a defined polarity. The assembly of RuvA and RuvB on the Holliday junction has been investigated by sedimentation analysis and by DNase I footprinting. We find that RuvA protein binds and protects all four strands of DNA at the crossover point, whereas RuvB protein binds the DNA asymmetrically. The polarity of branch migration is defined by the asymmetric assembly of the RuvAB branch migration complex relative to the junction and is consistent with a model in which RuvAB drives branch migration by passing the DNA through the hexameric rings of RuvB. PMID- 7889573 TI - A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. AB - To identify genes involved in cardiac arrhythmia, we investigated patients with long QT syndrome (LQT), an inherited disorder causing sudden death from a ventricular tachyarrythmia, torsade de pointes. We previously mapped LQT loci on chromosomes 11 (LQT1), 7 (LQT2), and 3 (LQT3). Here, linkage and physical mapping place LQT2 and a putative potassium channel gene, HERG, on chromosome 7q35-36. Single strand conformation polymorphism and DNA sequence analyses reveal HERG mutations in six LQT families, including two intragenic deletions, one splice donor mutation, and three missense mutations. In one kindred, the mutation arose de novo. Northern blot analyses show that HERG is strongly expressed in the heart. These data indicate that HERG is LQT2 and suggest a likely cellular mechanism for torsade de pointes. PMID- 7889574 TI - SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. AB - Long QT syndrome (LQT) is an inherited disorder that causes sudden death from cardiac arrhythmias, specifically torsade de pointes and ventricular fibrillation. We previously mapped three LQT loci: LQT1 on chromosome 11p15.5, LQT2 on 7q35-36, and LQT3 on 3p21-24. Here we report genetic linkage between LQT3 and polymorphisms within SCN5A, the cardiac sodium channel gene. Single strand conformation polymorphism and DNA sequence analyses reveal identical intragenic deletions of SCN5A in affected members of two unrelated LQT families. The deleted sequences reside in a region that is important for channel inactivation. These data suggest that mutations in SCN5A cause chromosome 3-linked LQT and indicate a likely cellular mechanism for this disorder. PMID- 7889575 TI - Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. AB - Murine cells homozygous for the severe combined immune deficiency mutation (scid) and V3 mutant hamster cells fall into the same complementation group and show similar defects in V(D)J recombination and DNA double-stranded break repair. Here we show that both cell types lack DNA-dependent protein kinase (DNA-PK) activity owing to defects in DNA-PKcs, the catalytic subunit of this enzyme. Furthermore, we demonstrate that yeast artificial chromosomes containing the DNA-PKcs gene complement both the DNA repair and recombination deficiencies of V3 cells, and we conclude that DNA-PKcs is encoded by the XRCC7 gene. As DNA-PK binds to DNA ends and is activated by these structures, our findings provide novel insights into V(D)J recombination and DNA repair processes. PMID- 7889576 TI - The roles of magnesium in biotechnology. AB - This review highlights the important roles played by magnesium in the growth and metabolic functions of microbial and animal cells, and therefore assigns a key role for magnesium ions in biotechnology. The fundamental biochemical and physiological actions of magnesium as a regulatory cation are outlined. Such actions are deemed to be relevant in an applied sense, because Mg2+ availability in cell culture and fermentation media can dramatically influence growth and metabolism of cells. Manipulation of extracellular and intracellular magnesium ions can thus be envisaged as a relatively simplistic, but nevertheless versatile, means of physiological cell engineering. In addition, biological antagonism between calcium and magnesium at the molecular level may have profound consequences for the optimization of biotechnological processes that exploit cells. In fermentation, for example, it is argued that the efficiency of microbial conversion of substrate to product may be improved by altering Mg:Ca concentration ratios in industrial feedstocks in a way that makes more magnesium available to the cells. With particular respect to yeast-based biotechnologies, magnesium availability is seen as being crucially important in governing central pathways of carbohydrate catabolism, especially ethanolic fermentation. It is proposed that such influences of magnesium ions are expressed at the combined levels of key enzyme activation and cell membrane stabilization. The former ensures optimum flow of substrate to ethanol and the latter acts to protect yeasts from physical and chemical stress. PMID- 7889577 TI - Atropine and succinylcholine: beliefs and controversies in paediatric anaesthesia. PMID- 7889578 TI - Post-herniorrhaphy pain in outpatients after pre-incision ilioinguinal hypogastric nerve block during monitored anaesthesia care. AB - The objective of this study was to evaluate the effect of an ilioinguinal hypogastric nerve block (IHNB) with bupivacaine 0.25% on the postoperative analgesic requirement and recovery profile in outpatients undergoing inguinal herniorrhaphy with local anaesthetic infiltration. Thirty consenting healthy men undergoing elective unilateral inguinal herniorrhaphy procedures were randomly assigned to receive an IHNB with either saline or bupivacaine according to a double-blind, IRB-approved protocol. All patients received midazolam, 2 mg iv, and fentanyl 25 microgram iv, prior to injection of 30 ml of either bupivacaine 0.25% or saline through the oblique muscle approximately 1.5 cm medial to the anterior superior iliac spine. Subsequently, the surgeon infiltrated the incision site with a lidocaine 1% solution. Sedation was maintained during the operation with a variable-rate propofol infusion, 25-140 micrograms.kg-1.min-1. No significant differences were noted in the intraoperative doses of lidocaine, propofol and fentanyl in the two treatment groups. However, the pain visual analogue score at 30 min after entering the PACU was lower in the bupivacaine (versus saline) group (P < 0.05). Although the times to ambulation (86 +/- 18 vs 99 +/- 27 min) and being judged "fit for discharge" (112 +/- 49 vs 126 +/- 30 min) were similar in the two groups, the bupivacaine-treated (vs saline) patients required less oral analgesic medication after discharge (46% vs 85%). We concluded that the use of an ilioinguinal-hypogastric nerve block with bupivacaine 0.25% as an adjuvant during inguinal herniorrhaphy under monitored anaesthesia care decreased pain in the PACU and oral analgesic requirements after discharge from the day-surgery unit. PMID- 7889579 TI - Mivacurium-induced neuromuscular blockade during sevoflurane and halothane anaesthesia in children. AB - The neuromuscular blocking effects of mivacurium during sevoflurane or halothane anaesthesia was studied in 38 paediatric patients aged 1-12 yr. All received premedication with midazolam, 0.5 mg.kg-1 po and an inhalational induction with up to 3 MAC of either agent in 70% N2O and O2. The ulnar nerve was stimulated at the wrist by a train-of-four stimulus every ten seconds and the force of adduction of the thumb recorded with a Myotrace force transducer. Anaesthesia was maintained with a one MAC end-tidal equivalent of either volatile agent for five minutes before patients received mivacurium (0.2 mg.kg-1) iv. The onset of maximal blockade occurred in 2.4 +/- 1.26 (mean +/- SD) min with halothane and 1.8 +/- 0.54 min with sevoflurane (NS). Four patients failed to achieve 100% block (3 halothane, 1 sevoflurane). The times from injection to 5, 75, and 95% recovery during sevoflurane (9.8 +/- 2.6, 19.5 +/- 4.4, and 24.2 +/- 4.8 min) were greater than during halothane anaesthesia (7.2 +/- 2.2, 15.0 +/- 4.0, 19.2 +/- 4.9 min, respectively (P < 0.005). All patients demonstrated complete spontaneous recovery of neuromuscular function (T1 > 95%, T4/T1 > 75%) during the surgery which lasted 24-63 min. All patients showed clinical signs of full recovery of neuromuscular blockade (i.e., headlift, gag, or cough). Pharmacological reversal was not required. It is concluded that following a single intubating dose of mivacurium, the time to maximum relaxation was not different during halothane and sevoflurane anaesthesia; recovery times to 5, 75 and 95% twitch height were longer during sevoflurane anaesthesia and neuromuscular reversal was not necessary. PMID- 7889580 TI - Comparison of tactile and mechanomyographical assessment of response to double burst and train-of-four stimulation during moderate and profound neuromuscular blockade. AB - It is common clinical practice to estimate the degree of neuromuscular blockade by tactile evaluation of twitch responses. The aim of the present study was to evaluate the use of tactile responses of adductor pollicis to double-burst stimulation (DBS) and train-of-four (TOF) peripheral nerve stimulation for monitoring moderate and profound levels of neuromuscular blockade. The study comprised 44 women scheduled for gynaecological laparotomy and anaesthetised with midazolam, fentanyl, thiopentone, halothane, nitrous oxide and atracurium. The tactile responses of the adductor pollicis were compared with mechanomyographical measurements in the contra lateral arm during recovery from neuromuscular blockade. The observers (anaesthetic nurses) of the tactile responses were blinded with regard to the stimulation pattern and the mechanomyographical measurements. The time from injection of the initial dose of atracurium until tactile reappearance of the first twitch in DBS (D1), was 24.6 (0-39.8) min, median (range). This was more rapid than the time until tactile reappearance of the first twitch in TOF (T1) 32.8 (18.2-43.4) min (P < 0.05). The median time from tactile reappearance of D1 until T1 recovered to 15% of the control twitch height was longer than the median time from tactile reappearance of T1 (14.6 versus 10.5 min) (P < 0.05). One or two responses to DBS or TOF were often felt before any responses had been detected mechanomyographically in the contralateral arm. When three or four responses to TOF were felt, responses were always detected mechanomyographically. It is concluded that tactile evaluation of responses ot DBS stimulation can estimate deeper levels of blockade than tactile evaluation of responses to TOF. PMID- 7889581 TI - Recovery of train-of-four after mivacurium. AB - The present study was designed to determine the time-course of recovery of the train-of-four (TOF) ratio during spontaneous recovery from mivacurium-induced block. Fifteen patients, free of neuromuscular disease, undergoing general endotracheal anaesthesia with isoflurane were studied. After anaesthetic induction, patients received a bolus dose of mivacurium 0.15 mg.kg-1. The TOF was then recorded continuously every 12 sec with a mechanogram (adductor pollicis monitor). When the TOF ratio recovered spontaneously to 0.9, an additional 0.05 mg.kg-1 of mivacurium was given. The durations required for recovery from a TOF ratio of 0.3 to 0.7 (DUR0.3-0.7) and from a TOF ratio of 0.3 to 0.9 (DUR0.3-0.9) were determined. The DUR0.3-0.7 averaged 7.0 +/- 2.5 min (range 3.4-12.2 min). The DUR0.3-0.9 averaged 11.8 +/- 3.9 min (range 6.0-20.2 min). There was no evidence of prolongation of recovery times (cumulation) following repeated dosing. The present data indicate that, in patients with normal cholinesterase activity (clinical duration 7-25 min), waiting 20 min beyond the time when fade is no longer apparent by visual or tactile evaluation is sufficient to attain a TOF ratio greater than 0.7-0.9 during spontaneous recovery from mivacurium, and may enable anaesthetists to avoid antagonism of mivacurium-induced block. PMID- 7889582 TI - Patient-controlled analgesia after laparoscopic and open cholecystectomy. AB - Laparoscopic cholecystectomy (LC) offers advantages over open cholecystectomy (OC) of more rapid patient recovery. The comparative amount of pain that patients must endure after each of these procedures is not clear. We retrospectively analysed the use of patient-controlled analgesia (PCA) of an unselected sample of patients having either LC or OC procedures to quantitate morphine use, as well as pain and sedation scores in the postoperative period. The hospital charts, anaesthetic records and the PCA records of 40 patients having either LC (n = 19) or OC (n = 21) were analysed retrospectively. The use of PCA morphine was standardized and consisted of a loading dose of 5 mg, bolus doses of 1.5 mg and a lockout period of five minutes. By the morning of postoperative day one, OC patients had used 38.0 +/- 11.7 (mean +/- SD) mg compared with 23.7 +/- 15.3 mg in LC patients (P < 0.05). The rates of PCA morphine use in the first two postoperative hours were 4.66 +/- 2.6 mg.hr-1 and 7.04 +/- 2.7 mg.hr-1 for LC and OC patients, respectively (P < 0.05). The rates of morphine use averaged over the day of surgery were 1.28 +/- 0.8 mg.hr-1 and 2.33 +/- 0.8 mg.hr-1 for LC and OC patients (P < 0.05). Despite higher PCA morphine use in OC patients, their pain scores were higher while their sedation scores were comparable. These data suggest that laparoscopic cholecystectomy is associated with less pain than open cholecystectomy in the day after surgery. PMID- 7889583 TI - Patient-controlled analgesia following caesarean section under general anaesthesia: a comparison of fentanyl with morphine. AB - This prospective, randomised, double-blind study compared PCA fentanyl with PCA morphine for post-Caesarean section analgesia. Following a standardised general anaesthetic, 37 women were allocated to receive either fentanyl (n = 18) or morphine (n = 19). The PCA was commenced after the women had been made comfortable in the postanaesthetic recovery room with the appropriate opioid solution (mean dose required = fentanyl 375 micrograms or morphine 16 mg). Initial PCA settings were bolus 1 ml (fentanyl 25 micrograms or morphine 1 mg), lockout time ten minutes, and no background infusion. Both analgesic solutions provided effective analgesia for a mean of 37 hr with high levels of patient satisfaction, and there were no differences in VAS scores for pain and patient satisfaction, or for side effects (nausea, itch, and sleepiness) between fentanyl or morphine. However, more patients in the fentanyl group required supplementary boluses or alterations to the PCA settings (13/18 vs 4/19: P = 0.005), and one patient was removed from the study due to inadequate analgesia. We conclude that fentanyl is not recommended for routine PCA use following Caesarean section. PMID- 7889584 TI - Cardiac enzymes in patients undergoing caesarean section. AB - Some of the changes reported in the ECG of parturients undergoing Caesarean section are suggestive of myocardial ischaemia. This study determined serum CK total and the isoenzyme CK-MB levels in 21 patients during and after Caesarean section under epidural anaesthesia. Twenty patients complained of chest pain, discomfort and pressure, while 12 had ST segmental depression. Although the total CK activity in ten patients was elevated, CK-MB activity in all patients was negative. The electrocardiographic changes were rate-related and occurred at the time pressure was placed upon the upper abdomen and lower thoracic cage by the surgeon to facilitate Caesarean delivery. The data from this study demonstrate that no myocardial injury as measured by CK-MB activity occurs in parturients undergoing Caesarean delivery despite the complaint of chest pain, discomfort and pressure, and ST changes in the ECG. PMID- 7889586 TI - Sonoclot coagulation analysis and plasma exchange in a case of meningococcal septicaemia. AB - On the basis of a patient with fulminant meningococcaemia and severe disseminated intravascular coagulation (DIC) syndrome, the diagnostic potential of a clot impedance test - Sonoclot coagulation analysis - was used to evaluate plasma exchange. A 17-yr-old girl was treated for a fulminant infection with Neisseria meningitidis in our intensive care unit. She developed severe DIC. Whereas platelet administration caused immediate arterial oxygen desaturation necessitating ventilatory support, plasma exchange improved pulmonary and mental function. Three separate exchanges all improved haemostasis. Sonoclot analysis was used together with routine coagulation analyses to evaluate this DIC treatment. Sonoclot signs, such as lack of the shoulder and peak, prolonged shoulder-peak interval and peak time predicted clinical bleeding manifestations (haematuria, haemoptysis, epistaxis) and were improved by platelet transfusion and plasma exchange. Plasma exchange was successful even at a very low platelet count of < 23 x 10(9).L-1. Sonoclot coagulation analyses were normalised several days before routine coagulation analyses. The Sonoclot gave additional information to routine coagulation studies, correctly indicated insufficient haemostasis and predicted a positive outcome. Also, plasma exchanges and platelet transfusions could be controlled in the management of DIC. PMID- 7889585 TI - Cardiopulmonary function and laparoscopic cholecystectomy. AB - This review analyzes the literature dealing with cardiopulmonary function during and pulmonary function following laparoscopic cholecystectomy in order to describe the patterns of changes in these functions and the mechanisms involved as well as to identify areas of concern and lacunae in our knowledge. Information was obtained from a Medline literature search and the annual meeting supplements of Anesthesiology, Anesth Analg, Br J Anaesth, and Can J Anaesth. The principal findings were that changes in cardiovascular function due to the insufflation are characterized by an immediate decrease in cardiac index and an increase in mean arterial blood pressure and systemic vascular resistance. In the next few minutes there is partial restoration of cardiac index and resistance but blood pressure and heart rate do not change. The pattern is the result of the interaction between increased abdominal pressure, neurohumoral responses and absorbed CO2. Pulmonary function changes are characterized by reduced compliance without large alterations in PaO2, but tissue oxygenation can be adversely affected due to reduced O2 delivery. A major difficulty in maintaining normocarbia is due to the abdominal distention reducing pulmonary compliance and to CO2 absorption. End tidal CO2 tension is not a reliable index of PaCO2, particularly in ASA III-IV patients. The pattern of lung function following LC is characterized by a transient reduction in lung volumes and capacities with a restrictive breathing pattern and the loss of the abdominal contribution to breathing. Atelectasis also occurs. These changes are qualitatively similar to but of a lesser magnitude than those following "open" abdominal operations. It is concluded that the changes in cardiopulmonary function during laparoscopic upper abdominal surgery lead us to suggest judicious invasive monitoring and careful interpretation in ASA III-IV patients. Lung function following extensive procedures in sick patients has not been reported. PMID- 7889587 TI - Transurethral resection syndrome after transurethral resection of bladder tumours. AB - The transurethral resection syndrome has not previously been described after bladder surgery. This article reports four patients who developed signs of this syndrome after transurethral resection of bladder tumours (TURB). Symptoms included abdominal pain, arterial hypotension, nausea and vomiting. There was evidence in all cases that the cause was absorption of irrigating fluid by the extravascular route. Fluid absorption was detected by ethanol in two patients and the urologist noted a perforation during the third operation. The most complicated clinical course occurred in the case where there was a delay of three hours before the diagnosis was made. Medical treatment consisted of antiemetics and volume expansion of the extracellular fluid compartment as extravasation is associated with hypovolaemia. Diuretics were not given until the circulation had been restored. PMID- 7889588 TI - Ankylosing spondylitis: lateral approach to spinal anaesthesia for lower limb surgery. AB - We describe three patients with long-standing ankyolsing spondylitis (AS) who underwent lower limb joint surgery under spinal anaesthesia. At preoperative assessment, it was considered that intubation of the trachea was likely to be difficult or impossible and previous general anaesthesia was associated with increased morbidity. Midline approach spinal anaesthesia failed but the lateral approach was successful. Spinal anaesthesia was induced using a 24 gauge Sprotte (Pajunk) needle with 3.5 ml heavy bupivacaine 0.5% at the L3-4 interspace with the patients in the sitting position. This resulted in adequate sensory blockade for the surgical procedure. None of the patients required airway interventions but equipment and aids to secure airway were available. PMID- 7889589 TI - Epidural analgesia for labour in a patient with Ebstein's anomaly. AB - Ebstein's anomaly is an uncommon congenital cardiac defect which is associated with cyanosis and arrhythmias. There have been very few previous reported cases of successful outcome in pregnancy in women with this disorder. We describe the successful analgesic management of an obstetric patient who had been known to have Ebstein's anomaly since childhood. Her first pregnancy was uneventful and analgesia during labour was provided by an epidural. During her second pregnancy she presented to our hospital as her condition had deteriorated. Symptomatic control was achieved with digoxin. Despite this, several episodes of hospitalization were needed pre-partum for rest and oxygen therapy. After the onset of spontaneous labour, analgesia was managed by an epidural using bupivacaine. Invasive monitoring was not deemed appropriate due to increased risk and questionable usefulness. Vaginal delivery was managed with elective lift-out forceps to minimize the stress of pushing. When reviewed two months post-partum she still required digoxin although her symptoms had improved considerably. The successful management of Ebstein's anomaly in pregnancy should include team management from early in pregnancy. PMID- 7889590 TI - Amrinone improves contractility of fatigued diaphragm in dogs. AB - The effects of amrinone, a bipyridine derivative, on diaphragmatic contractility and fatigue were examined in 36 anaesthetized, mechanically ventilated dogs divided into four groups. In Group Ia (n = 8), dogs without diaphragmatic fatigue were given a bolus injection (0.75 mg.kg-1) followed by continuous infusion (10 micrograms.kg-1.min-1) of amrinone iv. In Group Ib (n = 8), animals without fatigue received infusion only of maintenance fluid. In Group IIa (n = 10) and Group IIb (n = 10), diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. After producing fatigue, amrinone (0.75 mg.kg-1 loading dose plus 10 micrograms.kg-1.min-1 maintenance dose) iv were administered in Group IIa. Only maintenance fluids were administered in Group IIb during this period. Diaphragmatic contractility was assessed in each group by measuring transdiaphragmatic pressure (Pdi). Compared with Group Ib, Pdi at any stimuli in Group Ia did not differ. After producing fatigue, in Group IIa and Group IIb, Pdi decreased at low-frequency (10-30 Hz) stimulation (P < 0.05), whereas no change in Pdi was observed at high-frequency (50-100 Hz) stimulation. In Group IIa, Pdi to each stimulus increased during amrinone infusion compared with Group IIb (p < 0.05). In Group IIb, the speed of recovery from fatigue was relatively slower at low-frequency stimulation. The integrated diaphragmatic electric activity (Edi) did not change throughout the experiment. These results indicate that amrinone improves contractility in the fatigued diaphragm. PMID- 7889591 TI - Why was the urine green? PMID- 7889593 TI - International Federation of Clinical Chemistry. Use of artificial intelligence in analytical systems for the clinical laboratory. IFCC Committee on Analytical Systems. AB - The incorporation of information-processing technology into analytical systems in the form of standard computing software has recently been advanced by the introduction of artificial intelligence (AI) both as expert systems and as neural networks. This paper considers the role of software in system operation, control and automation and attempts to define intelligence. AI is characterized by its ability to deal with incomplete and imprecise information and to accumulate knowledge. Expert systems, building on standard computing techniques, depend heavily on the domain experts and knowledge engineers that have programmed them to represent the real world. Neural networks are intended to emulate the pattern recognition and parallel-processing capabilities of the human brain and are taught rather than programmed. The future may lie in a combination of the recognition ability of the neural network and the rationalization capability of the expert system. In the second part of this paper, examples are given of applications of AI in stand-alone systems for knowledge engineering and medical diagnosis and in embedded systems for failure detection, image analysis, user interfacing, natural language processing, robotics and machine learning, as related to clinical laboratories. It is concluded that AI constitutes a collective form of intellectual property and that there is a need for better documentation, evaluation and regulation of the systems already being used widely in clinical laboratories. PMID- 7889592 TI - The laryngeal mask airway--a consideration for the Neonatal Resuscitation Programme guidelines? PMID- 7889594 TI - An improved bromide assay for the estimation of extracellular water volume by capillary gas chromatography. AB - A sensitive bromide determination has been developed that consists of the following steps: isolation (purification) of bromide; oxidation of bromide to bromine with potassium permanganate and subsequent reaction with acetone, to give the volatile bromoacetone; quantification of bromoacetone by capillary gas chromatography. The method can also be used with small sample volumes appropriate for paediatric applications. Thermodynamic arguments are used to calculate the equilibria involved. The accuracy and reproducibility of the method have been determined. Finally, the bromide space of six volunteers was determined and the clearance of the bromide by the kidneys was investigated. PMID- 7889595 TI - Routine high-performance liquid chromatographic determination of urinary unconjugated cortisol using solid-phase extraction and ultraviolet detection. AB - An HPLC method with solid-phase extraction for the specific determination of urinary free cortisol is described. A 3-ml urine sample is cleaned up on a disposable cartridge C 18. After successive washing with 0.025 mol/l borate buffer (pH 7.5) and a mixture of acetone and water, retained cortisol and 6 alpha methylprednisolone (internal standard) are eluted with ethyl acetate. The recovery of cortisol is 92.9 +/- 4.4%. The reversed-phase chromatographic procedure uses an octadecyl-bonded column with a mobile phase composed of methanol, tetrahydrofuran and water with UV detection at 245 nm. The calibration curve is linear up to a cortisol concentration of 356 nmol/l. Coefficients of variation show good reproducibility of the assay. The detection limit is 9 nmol/l (16 pmol injected). The normal range of urinary free cortisol excretion was found to be 17-132 nmol/24 h. This simple and convenient method is suitable for routine use. PMID- 7889596 TI - Immunoheterogeneity of parathyroid hormone after surgery for primary hyperparathyroidism. AB - Circulating parathyroid hormone (PTH) immunoheterogeneity is altered in primary hyperparathyroidism (pHPT). It is not known, however, whether the relative secretion of various PTH fragments differs between the adenomatous and the non adenomatous glands in pHPT. We therefore examined the immunoheterogeneity of PTH in patients operated upon because of parathyroid adenoma pre- and 4 days postoperatively during an EDTA-infusion test. Following surgery, baseline levels of amino-terminal PTH (N-PTH) were reduced by a smaller degree than the levels of intact PTH (i-PTH) (P < 0.05) resulting in a higher N/i ratio postoperatively (P < 0.05). Furthermore, the increase in i-PTH and C-PTH fragments during the EDTA infusion test was lower postoperatively than preoperatively (P < 0.05), whereas the increase in N-PTH did not differ. The results therefore suggest that compared with the parathyroid adenoma, the non-adenomatous glands secrete relatively more N-terminal PTH. PMID- 7889597 TI - Competitive enzyme-linked immunosorbent assay of the human cholesteryl ester transfer protein (CETP). AB - The present report describes the first competitive enzyme-linked immunosorbent assay (ELISA) for the cholesteryl ester transfer protein (CETP), an enzyme playing an important role in lipoprotein metabolism. This assay was developed with well-characterized TP1 anti-CETP monoclonal antibodies. The sensitivity of the ELISA assay was comparable with the sensitivity of the previously described radioimmunoassays since 1 ng of CETP per microwell of the immunoplate could be detected. Intra- and inter-assay coefficients of variation were 4% and 6%, respectively. This enzyme immunoassay provides a specific, sensitive and reproducible method for measuring CETP concentrations in various biological samples. Within normolipidemic subjects, the mean (+/- S.D.) of the plasma CETP concentration was 2.77 (+/- 0.59) micrograms/ml with a range of 1.87 to 4.23 micrograms/ml. When plasmas were supplemented with fatty acid-free albumin, the positive correlation observed between plasma CETP mass and CETP activity was improved, suggesting that plasma non-esterified fatty acids could play a role in modulating the activity of the cholesteryl ester transfer protein. When applied to the study of the binding of CETP to lipoprotein substrates, the enzyme immunoassay revealed that the experimental protocol used to separate lipoprotein fractions can have a great influence on the plasma distribution of CETP. PMID- 7889598 TI - Hemoglobins S and C: reference values for glycohemoglobin in heterozygous, double heterozygous and homozygous subjects, as established by 13 methods. AB - Glycohemoglobin (gly-Hb) reference ranges of non-diabetic adults with HbAA (n = 17), HbAS (n = 37), HbAC (n = 22), HbSC (n = 8), HbSS (n = 6) and HbCC (n = 3) were determined by 13 methods, based on affinity chromatography, HPLC, electrophoresis and immunoassay. Gly-Hb of subjects with HbAS and HbAC can be measured without major difficulties by most methods. Some give rise to absolute gly-Hb differences > or = 1% compared with subjects with HbAA. Measurement of HbA1c/total Hb cannot be recommended. Some HPLC and immunoassay methods cannot measure gly-Hb in subjects with HbSC, HbSS and HbCC, whereas others may suffer from interference. Most methods showed low gly-Hb, reflecting increased erythrocyte turnover. Use of special reference ranges requires previous knowledge of the condition (affinity chromatography and immunoassay) or separation of gly Hb and its precursor Hb (HPLC and electrophoresis). Interpretation is, however, not recommended because of the numerous factors that determine erythrocyte turnover. PMID- 7889599 TI - Gamma-type gliadins cause secretion of prostaglandin E2 in patients with coeliac disease. AB - Coeliac disease is induced by polypeptides in the prolamin fraction of wheat, termed gliadin. It has previously been demonstrated that the alpha-, the beta- and the gamma-gliadin fractions contain toxic components and it has furthermore been strongly indicated that alpha-type gliadins are toxic. Due to insufficient protein separation methods there has been no information as to whether also the gamma-type gliadins are injurious in coeliac disease. We have therefore purified one alpha-type (alpha-39) and two gamma-type gliadins (gamma-36 and gamma-47) in a preparative scale by a combination of different ion exchange chromatographies. The purity was analyzed by high performance liquid chromatography and by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate, while the typing was based on determination of N-terminal amino acid sequence. Six patients with coeliac disease in remission were included in the study. Each of the purified gliadins was given by an intestinal perfusion technique to two patients. The perfusion fluid was collected and analyzed for the concentration of prostaglandin E2 (PGE2) as a marker for a toxic effect. All patients reacted with increased PGE2 secretion. For the first time it is clearly demonstrated that gamma-type gliadins are active in coeliac disease. PMID- 7889600 TI - Evaluation of enzyme inhibitors of cystinyl aminopeptidase and application to the measurement of immunoreactive atrial natriuretic peptide in human pregnancy. PMID- 7889601 TI - Improved method for quantitative analysis of lung surfactant phospholipids in bronchoalveolar lavage fluids by high-performance liquid chromatography. PMID- 7889602 TI - Investigation of obesity. PMID- 7889603 TI - Cabergoline: an advance in dopaminergic therapy. PMID- 7889604 TI - Radioiodine therapy of non-toxic multinodular goitre. PMID- 7889605 TI - Acute changes in thyroid volume and function following 131I therapy of multinodular goitre. AB - OBJECTIVE: Many textbooks claim that radioiodine (131I) treatment should be given with care to a goitre with substernal extension, for fear of acute swelling of the gland and thus respiratory problems. Since 131I is used increasingly in the treatment of non-toxic as well as toxic goitre we have evaluated the acute changes in thyroid volume following 131I therapy. DESIGN: Evaluation of potential acute changes in thyroid volume and function after 131I treatment in patients with non-toxic goitre treated because of compression symptoms or for cosmetic reasons, as well as in patients with toxic goitre. PATIENTS: Out-patients with multinodular goitre, either non-toxic (n = 20) or toxic (n = 10). Excluded were patients with a substernal goitre. MEASUREMENTS: Ultrasonically determined thyroid volume and standard thyroid function variables were investigated before and 2, 7, 14, 21, 28 and 35 days after treatment. RESULTS: In non-toxic goitres the thyroid volume did not increase significantly, the maximum increase in the median volume being 4% on day 7. Serum levels of free T3 and free T4 indices increased by 20% (day 7) and 13% (day 14) (P = 0.002), respectively. Likewise thyroid volume in toxic nodular goitre did not change significantly after 131I treatment (maximum median increase was 2%). None of the patients presented symptoms of tracheal compression. CONCLUSIONS: 131I treatment of non-toxic as well as toxic multinodular goitre does not seem to increase thyroid volume. PMID- 7889606 TI - Ultrasound guided percutaneous ethanol injection in the treatment of cystic thyroid nodules. AB - OBJECTIVE: The management of cystic lesions in the thyroid remains controversial. We examined the efficacy and safety of ultrasound guided percutaneous ethanol injection for the treatment of benign cystic thyroid nodules in euthyroid patients. STUDY DESIGN: (A) Preliminary randomized trial: 20 patients with predominantly cystic thyroid nodules were randomized in two groups and followed up for 1 month. Group 1 underwent fine needle aspiration of the fluid component of the nodules; Group 2 underwent percutaneous ethanol injection at the end of fine needle aspiration of the cyst fluid. (B) Prospective study: 32 patients with the same clinical characteristics (Group 3) were treated by fine needle aspiration and percutaneous ethanol injection, and followed up for 12 months. METHODS: Groups 1 and 2: clinical evaluation, thyroid ultrasonography, thyroid scintiscan and serum thyroid hormone profile were performed before treatment and one month later. Group 3: clinical evaluation, thyroid ultrasonography and serum thyroid hormone profile were performed in basal conditions and 1, 3, 6, 9, 12 months after treatment. Thyroid scintiscan was performed before treatment and 3-6 months later. RESULTS: (A) Randomized study: one month after treatment, nodule volume decrease in Group 2 was significantly higher than in Group 1 (Group 2: median 14.75 range 6-29.9 ml; Group 1: median 3.65 range 0.2-18.5 ml; P < 0.01). Nodule volume reduction was greater than 50% versus baseline in 8 (80%) patients in Group 2 and in 3 (30%) patients in Group 1 (P < 0.01). (B) Prospective study (Group 3): a significant nodule volume reduction (P < 0.01 vs pretreatment) was observed 1 and 12 months after percutaneous ethanol injection (pretreatment: median 14.5, range 1.5-65.8 ml; 1 month: median 3.5, range 0.4-38.9 ml; 12 months: median 2.5, range 0.4-34.5 ml). Nodule volume reduction greater than 50% was recorded in 24 (80%) patients. Groups 1-3: recurrence of cyst fluid was demonstrated by ultrasonography in 8 patients of Group 1, in 3 patients of Group 2 and in 1 patient of Group 3. No relevant adverse effects or significant biochemical changes were observed. CONCLUSIONS: Ultrasound guided percutaneous ethanol injection of cystic thyroid nodules is a safe, low-cost and effective therapeutic procedure in patients with benign thyroid cystic nodules. Indeed, nodule volume reduction was significantly greater and more frequent in patients treated by percutaneous ethanol injection than in those patients who underwent fluid aspiration alone. These results were confirmed in a long-term prospective trial and only one fluid recurrence was observed during 12 months of follow-up. PMID- 7889607 TI - Variability of serum thyroglobulin levels is determined by a major gene. AB - OBJECTIVE: There are large variations in the circulating concentrations of thyroglobulin. The purpose of this study was to explore the possibility of a genetic basis for the variability of serum concentration of thyroglobulin (Tg) in euthyroid individuals. DESIGN: The serum concentration of thyroglobulin (Tg) varies several-fold in euthyroid individuals. Other circulating proteins also show wide normal ranges of concentration and these variations have been shown to have a genetic as well as an environmental basis. To explore the possibility of a genetic basis for variability in serum Tg levels, an analysis was made of serum Tg levels in 44 pairs of identical twins and 66 nuclear families who were euthyroid and thyroid autoantibody negative (thereby eliminating subclinical autoimmune thyroid disease and Tg autoantibody interference with the Tg assay). RESULTS: Each pair of identical twins tended to have a similar Tg level and the overall correlation was highly significant (r = 0.734, P < 0.001). There was no relation between Tg and TSH levels in the twins (r = 0.119; P = 0.366). Segregation analysis of the 66 families showed that where both parents had Tg levels above the overall median for the subjects (males, 19 micrograms/l; females, 33 micrograms/l), 73% of the offspring also had concentrations above these levels, compared with 30% of the offspring when one parent had a high Tg level and only 16% in families where neither parent had a high Tg level. CONCLUSIONS: Complex segregation analysis using the computer program Pointer suggested that variability in Tg levels was the result of a major dominant-like gene effect (accounting for 80% of the variability) combined with a multifactorial component. Thyroglobulin, a template for thyroid hormone production, is also a major thyroid autoantigen and inherited variations in serum Tg levels may have implications for the pathogenesis of autoimmune thyroid disease. PMID- 7889608 TI - Dopamine and the sick euthyroid syndrome in critical illness. AB - OBJECTIVE: The sick euthyroid syndrome is a poorly understood hallmark of critical illness. Dopamine is a natural catecholamine with hypophysiotrophic properties, that is used as an inotropic agent of first choice in intensive care medicine. We explored the effect of dopamine infusion (5 micrograms/kg/min) on the sick euthyroid syndrome of critically ill patients. PATIENTS AND DESIGN: In a prospective, randomized, controlled and open-labelled study of critically ill, adult polytrauma patients (n = 12), we evaluated the effect of prolonged (83-296 hours) dopamine infusion (5 micrograms/kg/min i.v.) on the thyroid axis. The effect of brief (15-21 hours) dopamine administration was documented in an additional randomized, controlled, cross-over study involving 10 patients. The median age of the studied patients was 29 (16-83) years. MEASUREMENTS: Serum TSH concentrations were measured by IRMA. The TSH profiles were obtained by blood sampling every 20 minutes for 9 hours during two consecutive nights. Serum T4, T3 and reverse T3 concentrations were measured by RIA once per study night. RESULTS: Withdrawal of prolonged dopamine infusion was found to elicit a tenfold increase of serum thyrotrophin concentrations, a 57 and 82% rise of T4 and T3 respectively, and an increase of the T3/rT3 ratio, resulting in virtual normalization of the thyroid axis within 24 hours. The brief dopamine infusion was documented to have a suppressive effect on the thyroid axis within 24 hours. CONCLUSIONS: Dopamine infusion appears to induce or aggravate the sick euthyroid syndrome in critical illness. As a consequence, the sick euthyroid syndrome of severely ill patients receiving dopamine may be not an adaptive mechanism, but a condition of iatrogenic hypothyroidism. PMID- 7889609 TI - Oral progestogen-only contraception may protect against loss of bone mass in breast-feeding women. AB - BACKGROUND AND OBJECTIVES: A worldwide trend towards increasing life expectancy has meant that osteoporosis is emerging as an important public health problem. The loss of bone mineral density and its restoration in association with a premenopausal but physiological hypo-oestrogenic state may serve as an important model for research into the pathogenesis and prevention of osteoporosis. With this in mind we have undertaken a longitudinal study of changes in bone mineral density over one year in women after childbirth. DESIGN: Observational study of 31 women in the first year following childbirth; 11 intending to breast-feed and use barrier methods of contraception, 9 intending to breastfeed and to use the progestogen-only pill and 10 intending to artificially feed and to use barrier methods. PATIENTS: Recruitment was from the antenatal clinics of the Simpson Memorial Maternity Pavilion. Only non-smokers who had regular menstrual cycles prior to conception were included. MEASUREMENTS: Bone mineral density was measured at the lumbar spine within 3 weeks of childbirth and repeated at 6 and 12 months post partum. Plasma oestradiol, prolactin and osteocalcin concentrations were measured at each visit. RESULTS: Breast-feeding women using barrier methods lost a mean +/- SE of 4.9 +/- 1.5% of bone mineral density in the first 6 months following delivery. This was however reversible since by one year the bone mineral density was no different from that measured immediately post partum. Breast-feeding women using the progestogen-only pill lost a significantly smaller percentage of bone mineral density in 6 months and by one year bone mineral density was 2.95 +/- 0.75% higher than post partum. Artificially feeding women had a steady increase in bone mineral density in the first year and bone mineral density was on average 4.3 +/- 1.2% higher. CONCLUSION: Breast-feeding results in a reversible reduction in spinal bone mineral density. The small amounts of gestagen in the progesterone-only pill would appear to protect against this loss. The mechanism of this loss in bone mineral density and the potentially bone protective effects of gestagens require further study. PMID- 7889610 TI - Bone mineral density and metabolism in premenopausal women taking L-thyroxine replacement therapy. AB - BACKGROUND AND OBJECTIVE: Excess endogenous thyroxine causes bone loss, but the effects of exogenous thyroxine are disputed. We report on bone mass and metabolism in women taking L-thyroxine therapy. DESIGN: Cross-sectional and longitudinal studies. PATIENTS: Cross-sectional study: 40 healthy premenopausal women with autoimmune thyroiditis taking either physiological (serum TSH usually normal, 0.35-3.3 mU/l) or suppressive (serum TSH usually < 0.35 mU/l) doses of L thyroxine; patients were also compared with previously acquired age and weight matched premenopausal volunteers with no history of thyroid dysfunction. Longitudinal study: 28 patients were followed-up > or = 1 year later. MEASUREMENTS: In all subjects bone mineral density (BMD) was measured at the anteroposterior lumbar spine and left hip (femoral neck, greater trochanter and Ward's area) using dual-energy X-ray absorptiometry, and physical activity assessed using the Framingham physical activity index. Serum osteocalcin (OC), PTH and vitamin D, and urinary pyridinoline and deoxypyridinoline excretion were measured in patients. RESULTS: Cross-sectional study: The patient groups were well matched for disease duration and physical activity although the suppressed group were slightly younger (mean 38.1 (SD 7.5) vs 43.3 (3.9) years, P < 0.05). BMD, serum OC, PTH and vitamin D, and urinary cross-link excretion did not differ significantly between the two groups. Multivariate analysis of the whole group suggested that BMD at the femoral neck and greater trochanter was related positively to weight and physical activity and negatively to thyroxine dose (microgram/kg/day) and patient age. At the lumbar spine BMD was reduced non specifically in the presence of thyroid disease and treatment, but this effect appeared to decline with increasing duration of therapy. A similar analysis of the patient group suggested that urinary cross-link excretion correlated positively with thyroxine dose, and negatively with duration of treatment. Longitudinal study: Annualized changes in BMD were inversely related to thyroxine dose (microgram/kg/day) at all sites but achieved statistical significance only at the femoral neck and Ward's area. CONCLUSION: We did not find any effect of persistent historical TSH suppression on current bone mass, and this might relate to the relative insensitivity of older TSH assays. However, the cross-sectional and longitudinal data suggest that high daily doses of thyroxine in relation to patient body weight might adversely affect bone mass, particularly at the hip. These findings support the contention that excess exogenous thyroxine might predominantly deplete skeletal sites, such as the femoral neck, rich in cortical bone. PMID- 7889611 TI - Eighty-six cases of Addison's disease. AB - OBJECTIVES: Since there have been no recent reviews of Addison's disease, we have undertaken a retrospective case-notes review of all identifiable cases in Nottingham to define the prevalence, incidence and causes of Addison's disease. We have also reviewed the criteria for interpretation of the short Synacthen test in diagnosis. DESIGN: A retrospective study of all patients coded for the diagnosis and admitted to Nottingham's hospitals between 1 April 1987 and 31 March 1993, identified by the hospital Information Services. PATIENTS: A total of 86 cases were identifiable of whom 66 were still alive and living in the town. RESULTS AND CONCLUSIONS: The calculated prevalence was 110 per million population. The cause was attributed to autoimmune destruction of the adrenal cortex in 81 (93%). There were two cases of metastatic malignancy and three unrelated cases of late onset adrenoleukodystrophy, but none were attributable to tuberculosis. Twenty-one new cases were diagnosed between 1987 and 1993. The calculated incidence was 5.6 per million per annum. The biochemical basis of the diagnosis was reviewed in these 21 patients and as a result firm criteria are suggested for the interpretation of the short Synacthen test; criteria for normality being baseline cortisol >250 and 30 minute peak >600 nmol/l, taking into account clinical circumstances. PMID- 7889612 TI - Amplification of nocturnal melatonin secretion in women with functional secondary amenorrhoea: relation to endogenous oestrogen concentration. AB - BACKGROUND AND OBJECTIVE: Although there is extensive evidence that melatonin inhibits gonadotrophin secretion in animals, there is a parity of data on the relation between melatonin and ovarian function in humans. The purpose of this study was to evaluate the relation between endogenous oestrogen concentrations and nocturnal melatonin secretion occurring in patients with secondary amenorrhoea (SA). DESIGN AND PATIENTS: Nocturnal serum melatonin concentrations were determined in 20 women with SA, 5 women with endometriosis showing normal menstrual cycles and 11 volunteers with normal menstrual cycles. MEASUREMENT: Serum melatonin concentrations were determined by high performance liquid chromatography with electrochemical detection. Differences in melatonin concentrations were examined by analysis of variance. RESULTS: Nocturnal melatonin concentrations in patients with SA were significantly higher than in normal women (P < 0.01 vs women with normal menstrual cycles). There were significant negative correlations between cummulative melatonin levels (between 2000 and 0800 h) and serum 17 beta-oestradiol (r = -0.561, p < 0.01) and between peak serum melatonin values and the serum 17 beta-oestradiol (r = -0.608, P < 0.01) in SA. Intravenous administration of a conjugated oestrogen (Premarin 20 mg) significantly suppressed nocturnal melatonin secretion (P < 0.05). A low oestrogen state, induced by long-term (3.5 months) GnRH agonist treatment (900 micrograms/day of buserelin acetate) of the women with endometriosis produced an increase in nocturnal melatonin secretion comparable to that found in SA women. CONCLUSION: Our findings suggest that elevated nocturnal melatonin secretion in women with secondary amenorrhoea may be related to their low oestrogen concentrations. PMID- 7889613 TI - Serum inhibin during lactation: relation to the gonadotrophins and gonadal steroids. AB - OBJECTIVE: The aims of the study were to describe the changes in serum immunoreactive inhibin (INH) during normal lactation and to examine the relations between INH, oestradiol (E2) and follicle stimulating hormone (FSH), particularly during the first weeks post partum. DESIGN: Blood samples were obtained from normally lactating women for hormone measurements at daily intervals until discharge from hospital, and subsequently at weekly intervals until the resumption of menses, or one year post partum. SUBJECTS: Eighteen breast feeding women aged 27-36 years volunteered for the study. MEASUREMENTS: INH, FSH, luteinizing hormone (LH), prolactin (PRL), E2, and progesterone (P4) were measured by standard radioimmunoassays. Non-linear modelling was used to quantify the hormone patterns observed. RESULTS: Hormone levels were compared with those found in the follicular phase of the normal menstrual cycle. Levels of INH fell rapidly in the first week post partum and remained at the lower end of the follicular phase range for the period of study, rising only just prior to resumption of menses. E2 fell more slowly, into the follicular phase range, reaching the lower end of that range only at about approximately 100 days post partum. FSH levels were suppressed initially below the follicular phase range, commencing to rise 4.7-24 days post partum, reaching a plateau high in the follicular phase range 17.5-53 days post partum, and subsequently showing a slow decline. Human chorionic gonadotrophin (hCG), initially measured because of its cross-reactivity in the LH assay, fell rapidly post partum and LH remained in the low follicular phase range for several weeks. PRL fell slowly throughout and was still elevated at 150 days post partum, while P4 fell very rapidly and was less than 1 nmol/l until just prior to first menses. CONCLUSIONS: Inhibin levels fall rapidly post partum and remain low until close to the time of resumption of follicular activity and menses. The post partum rise in serum FSH appears to be much more closely related to falling oestradiol levels than to the very early and rapid fall in inhibin. Oestradiol thus appears to be the predominant negative feedback factor influencing FSH secretion during the post partum period. The low inhibin levels may allow FSH to rise to levels high in the follicular phase range under the predominant negative feedback control of oestradiol. Inhibin levels do not appear to be a suitable marker of returning fertility. PMID- 7889614 TI - Serotoninergic control of gonadotrophin and prolactin secretion in women. AB - OBJECTIVE: Due to conflicting observations from previous investigations, the role of serotonin (5-HT) in the regulation of the human menstrual cycle has not been clearly established. We have therefore investigated the possible participation of 5-HR in the control of gonadotrophin and PRL secretion in women, using the potent 5-HT3 receptor antagonist ondansetron as a pharmacological probe. DESIGN: Serum profiles of LH, FSH and PRL were obtained in 9 normally cycling women during a control and a treatment cycle, during which ondansetron (8 mg orally) was administered daily. On day 10 of both cycles, the serum pulsatility of LH, FSH and PRL was assessed by frequent blood sampling (at 10-minute intervals for 10 hours). Pituitary responsiveness was tested by administration of a GnRH bolus (25 micrograms i.v. after 8 hours). MEASUREMENTS: LH, FSH and PRL were serially determined in all blood samples by immunofluorescence assays. The resulting hormone data arrays were searched for significant fluctuations by the Cluster pulse algorithm. RESULTS: Compared with control cycles, the temporal organization and the endocrine characteristics of the treatment cycles remained virtually unaltered. Serotonin antagonism did not noticeably affect the LH pulse attributes (frequencies, interpulse intervals, amplitudes). Although FSH amplitudes declined markedly (P < 0.05), the remaining pulse attributes were unchanged. A clear increase (P < 0.05) in the PRL pulse frequency was noted, while PRL pulse amplitudes tended to increase (P = 0.1). Gonadotrophin and PRL release in response to GnRH administration was unaltered by ondansetron treatment. CONCLUSIONS: Serotoninergic blockade by a selective 5-HT3 receptor antagonist failed to modify pulsatile LH secretion, but induced distinct changes in episodic FSH and PRL secretion. Since the pituitary gonadotrophin and PRL responsiveness remained unaltered during 5-HT3 receptor blockade, the observed alterations in the FSH and PRL secretion presumably relate to altered hypothalamic regulation of these pituitary hormones. Thus, the central regulation of pulsatile FSH and PRL release in women appears to involve 5-HT3 receptor-mediated processes. PMID- 7889615 TI - Effects of follicular phase exercise on luteinizing hormone pulse characteristics in sedentary eumenorrhoeic women. AB - OBJECTIVE: Current studies reveal little regarding the inception of exercise induced LH changes during physical training. This study aimed to assess the susceptibility of the hypothalamic-pituitary axis to the acute physical stress of exercise in untrained, physically inactive women. The acute effects of submaximal endurance exercise upon the pulsatile LH secretion in the follicular phase were compared with those accompanying leisurely strolling for a similar time period. SUBJECTS: All subjects were eumenorrhoeic, as determined by biphasic temperature patterns, detection of the urinary LH surge, and mid-luteal serum progesterone levels. Subjects were not physically active and had little history of strenuous exercise (VO2max = 38.0 +/- 1.8) (mean +/- SEM) ml/kg/min). DESIGN: All women completed a 13.5-hour pulsatility test which included three consecutive 20-minute runs on a treadmill at 50, 60 and 70% of the subjects' maximum oxygen uptake (n = 16). Six of these same subjects completed a separate test on another occasion in which one hour of leisurely strolling was substituted for exercise. Blood was sampled every 10 minutes via an indwelling cannula for 4.5 hours before and 8 hours after one hour of exercise and or strolling. MEASUREMENTS: A pulse algorithm (Pulsar) was used to quantify LH pulse characteristics. RESULTS: Exercise produced no significant effects upon LH pulse frequency or mean serum LH concentration. However, exercise of moderate intensity caused a significant increase in LH pulse amplitude (P < 0.05). Strolling produced no significant changes in LH secretion. CONCLUSION: Acute exercise of moderate intensity in the follicular phase of untrained women is an insufficient stimulus to inhibit the GnRH pulse generator in the post-exercise period, yet may produce a slight stimulatory effect on the amount of LH released per pulse. PMID- 7889616 TI - Dissociation of adrenal androgen and cortisol secretion in Cushing's syndrome. AB - OBJECTIVES: While ACTH may modulate adrenal androgen production, there is evidence that other factors are required. Cushing's disease and ectopic ACTH secretion provide a little utilized opportunity to examine adrenal androgen levels in conditions of ACTH excess. We have compared plasma cortisol values with plasma levels of androstenedione, dehydroepiandrosterone (DHEA), DHEA-sulphate (DHEAS), testosterone and an index of free testosterone, the testosterone/sex hormone binding globulin ratio, prior to treatment in patients with Cushing's syndrome. PATIENTS AND MEASUREMENTS: Plasma from 15 adult patients with Cushing's disease and three adults with the ectopic ACTH syndrome was obtained prior to treatment and submitted to specific immunoassays for the measurement of the above steroids. RESULTS: Plasma cortisol values of 15 patients with Cushing's disease (range 326-1140 nmol/l, normal range 190-690 nmol/l) were elevated in 9; in contrast, plasma androstenedione (4.1-11.3 nmol/l, normal range, men 2.1-7.7, women 3.3-9.9 nmol/l) was elevated in only two patients, plasma DHEAS (3.3-17.8 mumol/l, normal range, men 4.5-18.4, women 3.5-11.8 mumol/l) was elevated in only 4 patients and plasma DHEA (4.8-45.2 nmol/l, normal range 11-48 nmol/l) was normal or low in all 15 patients. Plasma androstenedione was markedly elevated (74 nmol/l) in one of three patients with ectopic ACTH syndrome, moderately elevated in another, and normal in the third patient. In contrast, plasma DHEA and DHEAS levels were suppressed in the patient with the highest androstenedione level and low or normal in the other two patients. CONCLUSIONS: These data suggest that ACTH alone does not control adrenal androgen secretion. The data also suggest that variability in the processing of proopiomelanocortin (the precursor of ACTH and related peptides) occurring in Cushing's disease and ectopic ACTH syndrome may account for differences in the relation of cortisol to androgens observed between the disorders and when compared to that in normal subjects. PMID- 7889617 TI - The effect of recombinant IGF-I on anterior pituitary function in healthy volunteers. AB - OBJECTIVE: Insulin-like growth factor-I is the mediator of many of the actions of GH and is a potent metabolic regulator. Recombinant IGF-I (rhIGF-I) is of potential value in the treatment of syndromes associated with either GH or insulin resistance. This study was designed to assess the effects of subcutaneous (s.c.) rhIGF-I on anterior pituitary function. DESIGN: Double-blind, placebo controlled, randomized cross-over study. The interval between investigations was 2 weeks. SUBJECTS: Twelve normal volunteers received on one occasion a single s.c. dose of 40 micrograms/kg rhIGF-I and on the other, placebo. MEASUREMENTS: Circulating levels were measured, over 24 hours, of GH, LH, FSH, PRL, TSH, cortisol, ACTH, glucose, IGF-I, IGF-II, insulin, C-peptides; IGF binding proteins by Western ligand blotting; total IGF bioactivity using FRTL-5 thyroid cells; and glucose by the glucose oxidase method. RESULTS: Recombinant IGF-I increased AUC for plasma IGF-I, measured by radioimmunoassay (rhIGF-I mean 7065 +/- SEM 33 vs 3895 +/- 204 micrograms/l, P < 0.0001) and IGF bioactivity (22.5 +/- 3.4 vs 14.2 +/- 1.8 U/ml, P < 0.001) but plasma IGF-II fell (9308 +/- 403 vs 11052 +/- 451 micrograms/l, P < 0.0001). There was no biochemical or clinical evidence of hypoglycaemia and no difference in mean glucose levels. No difference existed in AUC for GH, LH, FSH, ACTH and cortisol between rhIGF-I and placebo; additionally, pulse number and amplitude for GH and LH were unaffected. TSH fell following rhIGF-I (33.0 +/- 3.36 vs 42.5 +/- 5.98 mU h/l, P = 0.01). Both mean plasma C peptide (0.73 +/- 0.06 vs 0.91 +/- 0.05 nmol/l, P = 0.03), and insulin (10.81 +/- 1.02 vs 15.36 +/- 1.18 mU/l, P = 0.03) were lower following rhIGF-I. There was no change in IGFBPs. CONCLUSION: A single injection of 40 micrograms/kg of subcutaneous rhIGF-I does not cause hypoglycaemia. IGF bioactivity was increased without inhibition of GH secretion. The only change observed in anterior pituitary function was a fall in plasma TSH. PMID- 7889618 TI - p53 gene mutations in pituitary adenomas: rare events. AB - OBJECTIVE: Occult pituitary adenomas are said to occur in up to 20% of random autopsy examinations, yet the only oncogene known to be associated with pituitary adenomas, gsp, is found in only 40% of somatotrophinomas, a subtype that accounts for a minority of pituitary tumours. Mutations of the p53 tumour suppressor gene are thought to be involved in the pathogenesis of as many as 50% of all human cancers, including tumours of the central nervous system. The objective of this study was to determine whether p53 gene mutations are associated with pituitary adenomas. DESIGN AND PATIENTS: Fragments of pituitary adenoma tissue from 29 patients undergoing routine hypophysectomy for pituitary tumour were coated in cryostat embedding medium and frozen at -80 degrees C within 24 hours of resection. They consisted of 9 somatotroph, 4 corticotroph, 1 mammotroph and 15 endocrinologically inactive adenomas, all of the non-invasive clinical phenotype. Sequential frozen sections were subjected to in situ hybridization analysis for anterior pituitary hormone transcripts and examined histologically to ensure that the frozen sections used to generate DNA templates for polymerase chain reaction amplification were not contaminated with non-tumour tissue. MEASUREMENTS: p53 exons 7 and 8, within which 98% of substitution mutations are thought to occur, and exons 4-6 in tumours immunopositive for p53, were amplified by polymerase chain reaction and ligated into the vector pCR2. DNA from small-scale plasmid preparations of pCR2 containing cloned p53 exons from human pituitary adenomas was sequenced using an automated fluorescence-based system (DuPont Genesis 2000) and compared with wild-type sequence. Apparent mutations were confirmed or refuted by sequencing a further 2-4 clones isolated from the same template. RESULTS: Although immunocytochemical staining patterns for wild-type p53 varied markedly between different tumours, no mutations were identified in any of the exonic sequences examined. CONCLUSIONS: p53 mutations, at least within the high mutation domains of p53, occur infrequently in human pituitary adenomas. Increased steady-state levels of p53 protein identified immunocytochemically may be a consequence of binding to other cellular proteins in these tumours. PMID- 7889619 TI - Gs alpha and Gi2 alpha mutations in clinically non-functioning pituitary tumours. AB - BACKGROUND AND OBJECTIVE: Activating mutations of Gs alpha (gsp) and Gi2 alpha (gip) have been described in various endocrine neoplastic conditions. The objective of this study was to assess the prevalence of gsp and gip mutations in clinically non-functioning pituitary tumours (NFTs) and to compare the clinical phenotypic characteristics of tumours bearing G protein gene mutations with wild type tumours. DESIGN: Twenty-two NFTs and 20 normal anterior pituitary glands screened for G protein gene mutations. PATIENTS: Twenty-two patients; 14 female (median age 59 years, range 19-76) and 8 males (median age 66.5 years, range 50 77). MEASUREMENTS: Site-directed hybridization or direct sequencing of polymerase chain reaction amplified Gs alpha and Gi2 alpha DNA. RESULTS: G protein gene mutations were identified in 3/22 (13%) of NFTs. Two tumours demonstrated gsp mutations, one at codon 201 arginine to cysteine, and the second at codon 227 glutamine to arginine. Three tumours demonstrated gip mutations at codon 205 glutamine to arginine. Two tumours with gsp mutations also harboured gip mutations. All tumours with G protein gene mutations demonstrated local bone infiltration into the surrounding structures. CONCLUSIONS: G protein gene mutations have been demonstrated in a proportion of non-functioning pituitary tumours. The presence of dual gsp and gip mutations in two tumours suggests the possibility of multiple hits in a stepwise pathogenesis of pituitary neoplasia. PMID- 7889620 TI - Quinagolide efficacy and tolerability in hyperprolactinaemic patients who are resistant to or intolerant of bromocriptine. AB - OBJECTIVE: To audit the efficacy of quinagolide (CV205-502, Norprolac, Sandoz) in lowering prolactin, and its tolerability, in patients with bromocriptine resistance (BCR) or bromocriptine intolerance (BCI), in view of the paucity of results published in patients specifically with BCR or BCI, by collating results in our own patients with the reports in the literature. DESIGN: Open prospective, uncontrolled administration of quinagolide in patients with BCR (defined for this report as failure to attain normal prolactin levels after 4 months of bromocriptine at maximum tolerated doses), or BCI (defined as a patient request to cease bromocriptine treatment because of side-effects at doses that were required, or failed, to normalize PRL levels). MEASUREMENTS: Prolactin levels, menses or pregnancy, and side-effects. PATIENTS: Six with BCR, and six with BCI (microprolactinoma in 7, macroprolactinoma in 5), treated with quinagolide 75 micrograms nightly increasing incrementally to a maximum of 450 micrograms. One patient who had taken part in a multicentre study of quinagolide in macroprolactinomas had BCI, and 11 further patients in the endocrine clinic who had BCR or BCI were offered quinagolide therapy under named-patient compassionate arrangements. RESULTS: Normal prolactin in 4/5 with BCR (3/6 with side-effects, none of them quinagolide intolerant), and normal prolactin in 2/6 with BCI (4/6 with side-effects, two of them quinagolide intolerant). CONCLUSIONS: Results in our 12 patients are broadly in line with those in 51 patients with bromocriptine resistance and 39 with bromocriptine intolerance extracted from various published reports, which together suggest that prolactin can be normalized in 16% of patients with bromocriptine resistance by quinagolide in doses of 225 micrograms or less, and in a further 20% by higher doses up to 600 micrograms. In bromocriptine intolerance, prolactin was normalized by quinagolide in doses of 225 micrograms or less in 58% of published cases and in 3 more patients by higher doses up to 1050 micrograms. About half the patients with bromocriptine resistance or bromocriptine intolerance who are treated with quinagolide experience side-effects, and around 7% are quinagolide intolerant. Doses need not exceed 225 micrograms, until failure to respond at this dose level is demonstrated. PMID- 7889621 TI - Adrenocorticotrophin-independent unilateral macronodular adrenal hyperplasia occurring with myelolipoma: an unusual cause of Cushing's syndrome. PMID- 7889622 TI - Primary hyperparathyroidism masked by antituberculous therapy-induced vitamin D deficiency. AB - Antituberculous chemotherapy agents, particularly rifampicin and isoniazid, affect vitamin D metabolism and can create biochemical evidence of vitamin D deficiency. Vitamin D deficiency induces a state of resistance to parathyroid hormone. This study sought to explain the temporary resolution of hypercalcaemia and hypercalciuria, during antituberculous chemotherapy with rifampicin and isoniazid, in a subject with a surgically proven parathyroid adenoma and coincidental spinal tuberculosis. Serum ionized calcium, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, plasma parathyroid hormone, and 24-hour urine excretions of calcium, inorganic phosphorus and hydroxyproline were sequentially measured over a 3-year interval that included 18 months of antituberculous chemotherapy. Initial serum ionized calcium was 1.52 mmol/l (normal 1.20-1.35 mmol/l), 24-hour urine calcium excretion was 9.40 mmol/day (normal 1.25 to 7.50 mmol/day) and plasma intact PTH was 9.2 pmol/l (normal 0.0-4.5 pmol/l). During antituberculous chemotherapy the serum ionized calcium and 24-hour urine calcium excretion were normal but the plasma PTH rose to higher levels. Following completion of the chemotherapy, hypercalcaemia and hypercalciuria returned with levels similar to those observed pretreatment. Serum 25-hydroxyvitamin D was low at 6.25 nmol/l (normal 20 to 90 nmol/l) during antituberculous chemotherapy, but was normal before and after. Serum 1,25-dihydroxyvitamin D was normal throughout the 3-year interval. We conclude that the antituberculous chemotherapy induced relative vitamin D deficiency and resistance to parathyroid hormone action, thereby masking the hyperparathyroidism and hypercalcaemia until the chemotherapy was completed. PMID- 7889623 TI - Secondary hypoadrenalism with hypercalcaemia. PMID- 7889624 TI - Modalities of treatment for children with short stature. PMID- 7889625 TI - Serum cortisol is not an accurate predictor of the integrity of the hypothalamic pituitary-adrenocortical axis. PMID- 7889626 TI - Overdose of dopamine agonist CV205-502. PMID- 7889627 TI - Absence of mutations in the MEN2A region of the ret proto-oncogene in non-MEN 2A phaeochromocytomas. AB - OBJECTIVE: To determine the presence of abnormalities of the MEN2A region of the ret proto-oncogene in phaeochromocytomas/paragangliomas (PHAEO) of different aetiologies. DESIGN: Total RNA was extracted from tumours and used as templates for reverse transcriptase polymerase chain reactions. A ret primer pair, which encompasses the region which is mutated in the germ-line of patients with MEN 2A, was used. The resulting 262-bp product was sequenced. PATIENTS: Ten PHAEOs were examined. Four tumours were from von Hippel-Lindau disease patients; five were sporadic, isolated tumours; one from a patient with multiple endocrine neoplasia type 2A (MEN 2A). The medullary thyroid cancer from the single MEN 2A patient was also examined. RESULTS: A heterozygous TGC to CGC mutation of codon 634 (cysteine to arginine) was found in the PHAEO and medullary thyroid cancer from the MEN 2A patient. The 262-bp ret fragment was not found in two tumours (one malignant PHAEO and one secretory paraganglioma), although the intra-cellular ret tyrosine kinase domain was detected in these tumours. The cysteine codons were normal in all other non-MEN 2A PHAEOs. CONCLUSION: Mutations of key cysteine codons of the ret proto-oncogene may be specific to MEN 2A. PMID- 7889628 TI - Further increase in forearm cortical bone mineral content after discontinuation of growth hormone replacement. AB - OBJECTIVE: Growth hormone replacement of adults with childhood onset GH deficiency results in an increase in bone mineral density (BMD) after 6-12 months of GH replacement. By measuring BMD 12 months after discontinuation of GH replacement we aimed to investigate whether there is an effect of GH replacement on BMD persisting after GH has been withdrawn. DESIGN: BMD was measured 13 +/- 1 (mean +/- SE, range 11-16) months after discontinuation of GH replacement. PATIENTS: Ten adults, age 23.2 +/- 1.4 (range 18.8-32.4) years, with childhood onset isolated GH deficiency (2 idiopathic, 8 irradiation induced) who had previously completed a study of the effect of 12 months of GH replacement on BMD. MEASUREMENTS: Forearm cortical bone mineral content (BMC) was measured using single-photon absorptiometry at the proximal site of the distal forearm. Forearm integral BMC at the ultradistal site of the forearm and bone width at both proximal and ultradistal sites of the distal forearm were measured by the same technique. Vertebral trabecular BMD was measured using quantitative computed tomography. RESULTS: Forearm cortical BMC was significantly greater than that measured at the time of discontinuation of GH (1.48 +/- 0.04 vs 1.44 +/- 0.05 g/cm). There was no significant change in forearm integral BMC or in vertebral trabecular BMD after discontinuation of GH. There was no significant change in bone width at proximal and ultradistal sites of the distal forearm after discontinuation of GH. CONCLUSION: After discontinuation of GH replacement the further increase in forearm cortical bone mineral content without a significant increase in forearm bone width suggests that the increase in cortical bone mineral content is due to a persisting effect of previous GH replacement, and not to further spontaneous attainment of bone mass before peak bone mass is reached. These findings emphasize the importance of continuing to monitor bone mass after the stimulus to increase bone turnover has been withdrawn. PMID- 7889629 TI - Somatostatin receptor imaging in persistent medullary thyroid carcinoma. AB - OBJECTIVE: Somatostatin is secreted from thyroid C-cells and seems to play an important part in the regulation of calcitonin secretion. We therefore evaluated the usefulness of somatostatin receptor scintigraphy in the localization of tumour tissue in patients with persistent medullary thyroid carcinoma. DESIGN: A prospective clinical study. PATIENTS: The series consisted of 26 patients with elevated calcitonin levels after total thyroidectomy for histologically proven medullary thyroid carcinoma. METHODS: Somatostatin receptor scintigraphy using 111In-pentetreotide (Octreoscan) was performed in all patients and the results correlated with histology, ultrasonography, computerized tomography, magnetic resonance imaging, plain radiography, bone scintigraphy and selective venous catheterization. Calcitonin and carcinoembryonic antigen levels were measured. RESULTS: The sensitivity of somatostatin receptor scintigraphy for localization of persistent medullary thyroid carcinoma was 57% in patients with histologically proven disease. The results depended on tumour mass (low sensitivity (33%) in minimal residual disease) and on the location of metastases (insensitive in detecting liver metastases). CONCLUSIONS: Somatostatin receptor scintigraphy is of value as an additional diagnostic tool in localizing medullary thyroid carcinoma, especially pulmonary metastases. It is of minor importance in detecting minimal residual disease. PMID- 7889630 TI - Measurement of TSH receptor blocking immunoglobulins using 3H-adenine incorporation into FRTL-5 and JPO9 cells: use in a child with neonatal hypothyroidism. AB - OBJECTIVE: The aim of this study was to develop an assay for the measurement of thyroid blocking antibodies (TBAb), based on the ability of patient serum to inhibit TSH stimulated 3H-cAMP production following incubation of FRTL-5 or JPO9 cells with 3H-adenine. The assay was then used to evaluate a child born with neonatal hypothyroidism. DESIGN: The levels of TBAb, TSAb (thyroid stimulating antibodies), TBII (TSH binding inhibitory antibodies), and the thyroid antibodies anti-thyroid peroxidase and thyroglobulin antibodies were measured in both mother and child over a 6-month post-natal period. PATIENT: The assay for TBAb was used to evaluate a child born with neonatal hypothyroidism whose mother had a history of hypothyroidism due to Hashimoto's thyroiditis. A 99mTc pertechnetate scan showed no evidence of functioning thyroid tissue. At 20 months of age an ultrasound verified a normally positioned thyroid. RESULTS: Initially, high levels of TBII and antithyroid antibodies were present in the serum of both mother and child. In both, the levels of TSAb were undetectable but there were significant levels of TBAb. The levels of TBAb decreased to control levels in the child within 2 months of birth but remained elevated in the mother's serum. CONCLUSIONS: This case of neonatal hypothyroidism associated with the passage of thyroid blocking antibodies demonstrates the utility of this new assay in the differential diagnosis of neonatal hypothyroidism. PMID- 7889631 TI - Natural history of thyroid associated ophthalmopathy. AB - BACKGROUND: The natural history of thyroid associated ophthalmopathy is poorly documented, although it is widely thought that many cases improve spontaneously with time. This has important implications in the management of patients and is also a critical factor when assessing the effects of different treatments. OBJECTIVE: To document the natural history of thyroid associated ophthalmopathy, 59 patients were studied longitudinally and the severity of eye disease documented at regular intervals. METHODS: Fifty-nine patients with thyroid associated ophthalmopathy who had not received immunosuppressive or surgical treatment for their eye disease, were recruited from a combined thyroid-eye clinic. They were assessed at presentation and at 3-6-monthly intervals for a median of 12 months. The eyes were assessed by separate and objective measurements relating to the status of the eyelids, cornea, extraocular muscles, proptosis and optic nerve function. In addition, a scoring system based on the above measurements was used to grade the overall severity of eye disease. RESULTS: Thirteen patients (22%) improved substantially, 25 patients (42.4%) showed minor improvement, 13 patients (22%) did not change, and 8 patients (13.5%) deteriorated progressively, to the extent that immunosuppressive treatment was considered to be necessary. CONCLUSIONS: A significant proportion of patients with thyroid associated ophthalmopathy (64.4% in the present series) improve spontaneously so serial assessment plays an important part in deciding which patients require immunosuppressive treatment. These findings also support the view that clinical trials designed to test the efficacy of new treatments in thyroid associated ophthalmopathy should be scrupulously controlled to allow for the natural tendency towards remission. PMID- 7889633 TI - Effect of chronic daily oral administration of 17 beta-oestradiol and norethisterone on the isoforms of serum gonadotrophins in post-menopausal women. AB - OBJECTIVE: Chronic treatment with 17 beta-oestradiol (E2) implants has been found to counteract the formation of more acidic isoforms of the gonadotrophins in post menopausal women. Oral medication with an oestrogen in combination with a progestagen is a common hormone replacement therapy (HRT) in post-menopausal women. The present study investigated the effect of such a therapy on the concentration and charge of the gonadotrophin isoforms in serum. DESIGN: Serum samples were obtained from 20 post-menopausal women, mean age 60 years (range 50 72 years), treated with continuous daily oral medication of 2 mg E2 combined with 1 mg norethisterone acetate (NETA). FSH, LH and E2 in the serum was measured with fluoroimmunoassays. The median charge and charge heterogeneity of the FSH and LH isoforms were determined for each serum by electrophoresis in 0.1% agarose suspension. Sera from 20 post-menopausal women without a history of HRT served as controls. The results were compared with those from previous studies on post menopausal women treated with E2 implants and on women with normal menstrual cycles. RESULTS: The E2 level in the oral-E2 + NETA treated women was 198-610 pmol/l, within the range expected during the mid-luteal phase of the normal menstrual cycle and similar to that of the group of women with an E2 implant. The mean LH level was similar to that of the luteal phase of the cycle and significantly lower than that of the controls (P < 0.001), the E2 implant group (P < 0.001) and at the follicular phase of the cycle (P < 0.01). The mean FSH level was similar to that of the follicular phase and the E2 implant group but lower than that of the controls (P < 0.001) and higher than at the luteal phase of the cycle (P < 0.01). The mean values for median charge of both FSH and LH were less acidic than those of the controls (P < 0.001) but more acidic than those for the E2 implant group (P < 0.01; P < 0.001) and for different phases of the menstrual cycle (P < 0.05; P < 0.001). The mean degree of charge heterogeneity of FSH was larger (P < 0.01), while that of LH was smaller (P < 0.01), than for the controls. The mean concentrations of SHBG in the oral E2 + NETA group, the E2 implant group and the controls were similar. CONCLUSION: Chronic oral therapy with 2 mg 17 beta-oestradiol combined with 1 mg norethisterone in post-menopausal women efficiently decreased the serum gonadotrophin levels but only partly counteracted the formation of the more acidic isoforms of FSH and LH after menopause. The differences in the charge for both FSH and LH between the E2 implant and the oral E2 + NETA treated groups may be due to the differences in route of administration of E2 or to the effect of norethisterone or both. PMID- 7889632 TI - Loss of biological activity of arginine vasopressin during its degradation by vasopressinase from pregnancy serum. AB - BACKGROUND AND OBJECTIVE: Degradation of AVP by placental vasopressinase may precipitate gestational diabetes insipidus, which in some cases is accompanied by pre-eclampsia. Abnormally elevated vasopressinase has also been reported in pre eclampsia without diabetes insipidus. This association between excessive vasopressinase production and pre-eclampsia might be explained if the products of AVP degradation by vasopressinase retained pressor activity even after anti diuretic activity had been destroyed. Recent evidence indicates that such products may raise blood pressure in rats. The objective of this study was, therefore, to purify vasopressinase and investigate its action on both the V1 and V2 receptor-stimulating activity of AVP. DESIGN: Vasopressinase was purified from pooled pregnancy serum by ammonium sulphate precipitation, followed by sequential ion exchange, lentil lectin affinity and gel filtration chromatography. Purified enzyme was then used to degrade AVP and the loss of both immunoreactivity and biological activity monitored. Loss of V1 receptor-stimulating activity and V2 receptor-stimulating activity was compared by two-way ANOVA. PATIENTS: Blood was obtained from healthy women between week 34 and the end of pregnancy. Pooled serum from 20-30 patients was used as starting material for the purification of vasopressinase. MEASUREMENTS: AVP immunoreactivity was measured by radioimmunoassay, V1 receptor-stimulating activity by a platelet aggregation bioassay, and V2 receptor-stimulating activity by adenylate cyclase stimulation in LLC-PK1 target cells. RESULTS: Purified vasopressinase was a dimeric protein of molecular weight 330 kDa, which cleaved the synthetic substrate S-benzyl-L cysteine-4-nitroanilide with a Km of 0.33 mM. Incubation of AVP (0.1 mM) with vasopressinase (0.66 milligrams) at 37 degrees C led to a parallel loss of both AVP immunoreactivity and biological activity. The rates of loss of V1 and V2 receptor mediated activities were not significantly different. CONCLUSIONS: We report the first direct comparison between the loss of V1 and V2 receptor mediated activities of vasopressinase degraded AVP. There was no significant retention of V1, relative to V2, receptor mediated activity. AVP degradation products are unlikely to be pathogenic in hypertensive pregnancy. PMID- 7889634 TI - The acute effects of oral ethanol on the hypothalamic-pituitary-adrenal axis in normal human subjects. AB - OBJECTIVE: To evaluate the acute effects of oral ethanol on the hypothalamic pituitary-adrenal axis in normal human subjects and, in particular, to examine the effect of background alcohol intake and gastrointestinal side-effects on this response. DESIGN: Plasma ethanol, cortisol, ACTH, corticotrophin-releasing hormone (CRH) and AVP were measured half-hourly for 4 hours following 1.1 ml/kg of 95% ethanol or placebo in a cross-over study. At least one week elapsed between each procedure. SUBJECTS: Twelve healthy non-alcoholic volunteers with a wide range of background alcohol intakes. MEASUREMENTS: Peptide hormones were measured by radioimmunoassay, cortisol by ELISA and blood ethanol by headspace gas chromatography. Results are expressed as mean +/- SEM. RESULTS: Blood ethanol levels peaked at one hour post ethanol ingestion. Three subjects developed significant gastrointestinal (GI) side-effects, with two vomiting and one experiencing moderate to severe nausea. There was no difference between peak blood ethanol levels in the groups with and without GI side-effects (34.5 +/- 2.4 mmol/l vs 34.3 +/- 1.7 mmol/l respectively). ACTH and cortisol rose in those subjects who experienced GI side-effects (P < 0.0001 for each). The remaining subjects had a tendency for ACTH and cortisol to be higher on the placebo day. The group with GI side-effects following ethanol administration had a significant rise in AVP (P < 0.02) that was synchronous with ACTH and cortisol. No consistent alcohol related changes were seen in peripheral CRH levels, although there was a significant increase over time on both active and placebo days (P < 0.0001). In the group with no GI side-effects, AVP did not significantly fall in the first half hour following ethanol, while a significant fall did occur following placebo (P < 0.05). Plasma renin activity was, however, increased by ethanol (P < 0.05). The background alcohol intake of the group with GI side-effects was significantly lower than the group without (18 +/- 7 vs 235 +/- 51 g/week, P < 0.05), but no hormonal response was seen in two subjects with a relatively low alcohol intake (< 100 g/week) who did not experience GI side-effects. CONCLUSION: Intoxicating levels of ethanol per se do not result in activation of the hypothalamic pituitary-adrenal axis in humans. However, gastrointestinal side-effects induced by the ethanol do result in such activation, which appears to be mediated by AVP as the dominant ACTH secretagogue. One of the factors which influences the blood ethanol level at which GI side-effects occur appears to be background alcohol intake. PMID- 7889635 TI - Replacement treatment with biosynthetic human growth hormone in growth hormone deficient hypopituitary adults. AB - OBJECTIVES: The physiological role of growth hormone in adult life has recently attracted increased interest. We have studied the clinical effects and the effects on body composition of prolonged replacement with biosynthetic human GH in a large number of hypopituitary adults. DESIGN: A randomized double blind placebo controlled trial for 6 months followed by an open trial of GH treatment for 12 months. GH daily dose was 0.04 (0.02-0.05) IU/kg s.c. PATIENTS: Forty GH deficient hypopituitary patients (19 M, 21 F; aged 19-67 years) on conventional replacement therapy were studied. MEASUREMENTS: Serum insulin like growth factor I (IGF-I), skinfold thickness, total body potassium, total body water (TBW), exercise tolerance and muscle strength, and well-being. RESULTS: During the 6 month double blind phase, two GH treated patients withdrew because of adverse events. Lean body mass (LBM) increased and percentage body fat (%BF) decreased on GH but not on placebo (P) (LBM: (GH: from 48.5 +/- 9.6 to 49.6 +/- 9.5 kg; P: from 50.9 +/- 9.2 to 50.1 +/- 9.0 kg, P < 0.05 GH vs P) and %BF (GH: from 34.7 +/ 11.4 to 34.2 +/- 10.7; P: from 37.4 +/- 7.6 to 38.7 +/- 8.1, P < 0.05 GH vs P)). TBW increased on GH (P < 0.01) but not on P. No change was observed in waist-to hip ratio or in muscle strength. During longer-term follow-up combining the double blind and open phase components of the study, 34, 27 and 11 patients received GH for 6, 12 and 18 months respectively. Patients dropped out because of adverse events or lack of perceived benefit. Skinfold thicknesses decreased significantly at 6 and 12 months and the waist circumference at 6 months. Waist to-hip ratio decreased significantly on GH at 12 months. LBM increased on GH treatment from 49.6 +/- 9.1 to 51.6 +/- 9.4 kg (P < 0.0006), 51.9 +/- 8.9 kg (P < 0.07) and 53.1 +/- 10.5 kg (P < 0.0001) at 6, 12 and 18 months respectively. Percentage body fat decreased on GH from 37.2 +/- 10.7 to 34.7 +/- 10.1 (P < 0.005), 35.1 +/- 12.8 (NS) and 34.5 +/- 8.6 (P < 0.04) at 6,12 and 18 months respectively. TBW also increased at 6 and 12 months of GH treatment. Exercise time increased significantly at 6, 12 and 18 months of GH treatment. Muscle strength in selected muscle groups increased significantly at 6, 12 or 18 months of GH treatment. Randomization resulted in the placebo group having a greater GHQ score (higher morbidity) than the GH group before therapy. Over the controlled phase, GHQ scores improved on placebo but not on GH and CPRS score was unchanged in either group. In the open phase, the GHQ score did not change on GH therapy but CPRS score improved at 6 and 12 months. CONCLUSIONS: Growth hormone replacement therapy in adults for 6 months increased lean body mass, total body water and exercise tolerance, and decreased body fat. Growth hormone replacement for longer than 6 months maintains the advantageous effects seen in shorter-term studies and may have additional effects on body fat distribution, muscle strength and psychological well-being. PMID- 7889636 TI - Effect of glucocorticoid replacement therapy on glucose tolerance and intermediary metabolites in hypopituitary adults. AB - BACKGROUND AND OBJECTIVES: Excess impaired glucose tolerance and diabetes mellitus have been reported in hypopituitary adults on conventional replacement therapy including glucocorticoids. We investigated the effect of the glucocorticoid component on glucose tolerance and intermediary metabolites in hypopituitary adults. DESIGN: A 3-hour 75-g oral glucose tolerance test (OGTT) was performed on two study days, at least one week apart. On one study day, the glucocorticoid replacement morning dose was taken 60 minutes before the OGTT, and on the other it was left until after the OGTT. All other pituitary replacement therapies were kept unchanged on the two study days. PATIENTS: Eight hypopituitary adults (3 males and 5 females; aged 46-76 years) on conventional replacement therapy were studied. Their duration of hypopituitarism was mean (range) 15 (5-31) years. Their mean body mass index (BMI) was 28.4 (24.1-35.1) kg/m2. Their total daily cortisol dose was 26 (15-30) mg. MEASUREMENTS: Plasma glucose, insulin, non-esterified fatty acids (NEFA), glycerol and 3 hydroxybutyrate were measured at 30-minute intervals and plasma cortisol levels were measured hourly. RESULTS: Fasting glucose and insulin concentrations were similar on the glucocorticoid day (GD) and the non-glucocorticoid day (NGD) (glucose (mean +/- SD) 4.9 +/- 0.9 vs 4.4 +/- 0.5 mmol/l; insulin (median (range)) 5 (1-17) vs 2 (1-15) mU/l, respectively). Post-glucose glycaemia was higher on the GD than on the NGD with a significantly higher glucose area under the curve (AUC) (45.0 +/- 8.2 vs 38.9 +/- 11.7 mmol/l h, P < 0.05). Post-glucose insulinaemia was also higher on the GD than on the NGD with significantly higher insulin AUC (270 (47-909) vs 207 (46-687) mU/l h, P < 0.02). Impaired glucose tolerance was found in three patients on the GD, one of whom continued to have impaired glucose tolerance on the NGD. The areas under the curves of NEFA, glycerol and 3-hydroxybutyrate were not significantly different on the two days. On the NGD, plasma cortisol levels were undetectable (< 50 nmol/l) in all patients and on the GD the median (range) peak was 500 (330-740) nmol/l dropping to 125 (60-330) nmol/l at 180 minutes. The difference in glucose AUC between the two days correlated with the maximal plasma cortisol levels (Spearman's p = 0.83, P < 0.01). CONCLUSIONS: Glucocorticoid replacement therapy taken pre-prandially in hypopituitary adults induces mild elevations in circulating glucose and insulin levels even with acceptable plasma cortisol concentrations. Optimal regimens for glucocorticoid replacement require more study. PMID- 7889637 TI - Nifedipine, but not verapamil, acutely elevates parathyroid hormone levels in premenopausal women. AB - BACKGROUND: Calcium channel antagonist therapy in humans has been associated with changes in anterior pituitary, thyroid and adrenal hormone secretion. Human studies assessing effects of calcium channel antagonists on calciotropic hormones have been few and typically involved small numbers of subjects studied for short periods of time. Few of these previously published studies have included women. The endocrine effects of calcium channel antagonists in women have become increasingly important as more women are taking these agents for diseases such as hypertension, angina, Raynaud's phenomenon and migraine. OBJECTIVE: To assess both acute and chronic effects of calcium channel antagonists on calciotropic hormones in women. DESIGN: A four-week prospective, randomized trial. SUBJECTS: Twenty-nine premenopausal women, randomly assigned to receive either 240 mg of sustained release verapamil or 30 mg of sustained release nifedipine daily. LABORATORY END-POINTS: Total and ionized serum calcium, phosphate, creatinine, parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP) and calcitonin, measured at baseline, after 24 hours, and 28 days of treatment. RESULTS: Total and ionized calcium, phosphate, creatinine, PTHrP and calcitonin levels were not altered significantly after 24 hours or 28 days in any of the subjects, when compared to baseline. There were no significant differences in PTH levels after 24 hours or 28 days of verapamil treatment. There was a significant increase in serum PTH levels after 24 hours of nifedipine therapy; however, these differences were not evident after 28 days of therapy. CONCLUSIONS: The short term administration of nifedipine results in increased release of parathyroid hormone; however, long-term administration has no significant effect on the concentrations of calciotropic hormones. PMID- 7889638 TI - Megestrol-induced Cushing's syndrome. AB - This case describes the first report of a patient developing Cushing's syndrome whilst being treated with the synthetic progestogen, megestrol acetate (Megace). Drugs are the commonest cause of Cushing's syndrome. Some synthetic progestogens are known to have glucocorticoid activity at high doses. On structural grounds neither megestrol nor its major metabolites would be expected to interact with the glucocorticoid receptor, through the manufacturers report that it may have 'weak glucocorticoid activity'. PMID- 7889639 TI - Pseudo-phaeochromocytoma after multiple drug interactions involving the selective monoamine oxidase inhibitor selegiline. AB - A patient presented with paroxysmal hypertension and typical clinical features of phaeochromocytoma, but with a normal adrenal computed tomographic scan and much higher plasma noradrenaline than adrenaline concentrations. Urinary vanillylmandelic acid concentrations were only moderately elevated. This syndrome probably arose as a consequence of an interaction between the monoamine oxidase inhibitor selegiline, the sympathomimetic agent ephedrine, and a tricyclic antidepressant. The mechanism of the interaction is thought to be related to increased sympathetic release of noradrenaline by ephedrine, inhibition of catabolism by selegiline, and inhibition of reuptake of noradrenaline by the tricyclic. Although newer selective monoamine oxidase inhibitors are considered to be safer than earlier non-selective inhibitors, they can also contribute to drug interactions mimicking phaeochromocytoma. PMID- 7889640 TI - Etiological subgroups in non-syndromic isolated cleft palate. A genetic epidemiological study of 52 Danish birth cohorts. AB - Isolated cleft palate (CP) is considered to be a heterogeneous trait with an important genetic contribution to the etiology. Multifactorial-threshold models of non-syndromic CP inheritance assume a female predominance. The present study of 52 Danish birth cohorts, using several ascertainment sources, identified 2301 CP cases. It was found that, although females tended to be more severely affected than males, the overall sex ratio was close to one. For the latter half of the study period (1962-87), which probably had the best ascertainment, the sex ratio for non-syndromic CP was 0.95 (95% C.I. 0.85-1.07). Marked difference in sex ratios for non-syndromic overt CP including the hard palate (CPH) and non syndromic overt CP of the soft palate only (CPS) (0.69 vs 1.00, p < 1.00, p < 0.05) suggested that these two conditions may be etiologically distinct, a hypothesis which is embryologically plausible. In agreement with this hypothesis, Danish family data from surgically treated CP cases showed a strong tendency to segregate only one of the CP subtypes within families. Future studies are recommended to test the existence of a possible etiological difference between CPH and CPS. PMID- 7889641 TI - A stigmatizing effect of the carrier status for cystic fibrosis? AB - The emotional impact of carrier detection for CF was assessed in a group of adults tested before 1992. Of the 200 adults who received a mailed questionnaire, 70% participated. One third were CF gene carriers. The Health Orientation Scale (HOS) was used to evaluate perceived feelings about three situations: (a) How would you describe your feelings about yourself when you consider your test result? (b) How do you think most people feel when they are told that they carry the CF gene? (c) How do you think most people feel when they are told that they do not carry the CF gene? Comparing the profiles of CF carriers and non-carriers, we found that carriers had significantly less positive feelings about themselves than non-carriers. Carriers as well as non-carriers attribute significantly more negative feelings to most carriers of the CF gene than to most non-carriers. Moreover, carriers of the Cf gene attribute more negative feelings to other CF carriers than to themselves. Analysis of variance revealed a significant effect of carrier status on self-description, as well as a significant effect of carrier status and degree of kinship with a CF patient on feelings attributed to most carriers. Although these results suggest some danger of stigmatization of CF carriers, the cognitive bias of 'illusory superiority' seems to counterbalance some of its effects. PMID- 7889642 TI - Short tarsus--absence of lower eyelashes: an autosomal dominant condition. AB - We describe a four-generation Brazilian family with short tarsus and absence of the lower eyelashes, with normal intelligence. Autosomal dominant inheritance is evident. PMID- 7889643 TI - An epidemiological/genetic study of mental subnormality in Assiut Governorate, Egypt. AB - The aim of this investigation was to study the epidemiologic and genetic aspects of mental subnormality (MS) in Assiut Governorate, representing the Egyptian population. The sample comprised 3000 randomly selected subjects from three localities: one urban (Assiut City) and two adjacent rural villages. Age-matched controls were chosen for comparison. The Stanford-Binet test was administered to each individual. During history-taking special attention was paid to consanguinity and categorization on a genetic basis. The results revealed 116 cases with MS, showing an overall prevalence of 3.9%, which varied in the three locations: 3.4% in Assiut City, and 3.8% and 4.4% in the two rural locations. Clinico-genetic classification revealed the following: idiopathic MS 27.6%, MCA/MR syndromes 24.1%, primary CNS defect 12.9%, Martin-Bell syndrome 10.3%, inborn errors of metabolism 9.5%, tetratogenic and environmental causes 5.2%, MS and epilepsy 4.3%, chromosomal disorders 3.4% and MS associated with psychiatric disorder 2.6%. Parental consanguinity was found in 65% of the total sample, which emphasizes the role played by that factor in the etiology of mental subnormality in Egypt. PMID- 7889644 TI - Prenatal sex determination by in situ hybridization on fetal nucleated cells in maternal whole venous blood. AB - Our aim was to evaluate whether the sex of a fetus could be determined in maternal whole venous blood by in situ hybridization without enrichment of fetal cells. This procedure is virtually without risks to the fetus or the mother. Blood samples were obtained from 59 women at different stages of pregnancy. Twenty preparations were discarded because they were technically unfit for in situ hybridization. Of the remaining 39 pregnant women, 18 had a male fetus, one had male twins, and 20 had a female fetus. Y-positive cells were detected in 12 of the 19 pregnancies with male fetuses and in two of the 20 pregnancies with a female fetus. The frequencies of cells with Y-signals ranged from 1 in 100,000 to 1 in 639. Our results show that fetal cells in maternal blood cannot be reliably used for prenatal diagnosis without prior enrichment of fetal cells. PMID- 7889645 TI - Molecular characterisation of an Italian G6PD variant responsible for chronic non spherocytic haemolytic anaemia. AB - An Italian deficient G6PD variant associated with chronic non-spherocytic haemolytic anaemia (CNSHA) was biochemically characterised and studied at molecular level. Single-strand conformation polymorphism (SSCP) analysis led to the identification of an abnormal migration pattern of an amplified fragment encompassing exons 10 and 11 of the G6PD gene. Sequence analysis of both strands using an automated fluorescent DNA sequencer revealed a G-->A transition at nt. position 1246 in exon 10. A C-->T substitution at nt. 1311 in exon 11 was also found, which has already been described as a silent mutation common in Caucasians. The 1246 G-->A mutation has been described only in a Japanese subject with CNSHA (G6PD Tokyo) not associated with the 1311T polymorphism, suggesting that this mutation may have arisen independently in Europe and Asia. PMID- 7889646 TI - Familial translocation (X;3) (p22.3;p23): chromosomal in situ suppression (CISS) hybridization and inactivation pattern study. AB - High-resolution chromosome banding and chromosomal in situ suppression hybridization were used to identify a derivative X in a 10-month-old female patient with congenital heart defect and slight dysmorphism. The unbalanced karyotype was monosomic for Xp22.3-pter and trisomic for 3p23-pter regions. The derivative X was inherited from the mother carrier of a balanced translocation (X;3) (p22.3;p23). Replication study of the patient showed the abnormal X,t(X;3) to be late replicating, except for the translocated segment. This patient demonstrated only epicanthus and congenital heart defect, despite her partial trisomy 3. The clinical phenotype may be less severe when the X-chromosome is involved in an unbalanced translocation. PMID- 7889647 TI - Identification of a non-fluorescent isodicentric Y chromosome by molecular cytogenetic techniques. AB - A 12 1/2-month-old girl was referred because of short stature, short neck, large internipple distance and simian crease on her right hand. By routine cytogenetic techniques the presence of an unidentifiable marker chromosome and loss of one X chromosome was noted (i.e. 45, X/46, X, mar/47, X, mar, +mar). By fluorescence in situ hybridization (FISH) technique, the marker chromosome was identified as an isodicentric non-fluorescent Y chromosome ((45, X/46, X, idic (Ynf)/47, X, idic (Ynf), +idic (Ynf)). Although the clinical significance of this finding cannot be assessed at present, possible development of gonadoblastoma in such cases is a major concern and warrants follow-up evaluations. PMID- 7889648 TI - Patient with de novo 12p+ syndrome identified as dir dup (12) (p13) using subchromosomal painting libraries from somatic cell hybrids. AB - Several patients with partial 12p duplications are known. An additional patient, who presented with the clinical manifestations of trisomy 12p syndrome, is described. De novo duplication 12p13.1-->pter was diagnosed using subchromosomal painting libraries obtained from somatic cell hybrids. PMID- 7889649 TI - Antley-Bixler syndrome: report of a patient and review of literature. AB - We report a patient with Antley-Bixler syndrome and review 13 patients from the literature. The cardinal features of this condition include craniosynostosis, severe mid-face hypoplasia, proptosis, choanal atresia/stenosis, frontal bossing, dysplastic ears, depressed nasal bridge, radiohumeral synostosis, long-bone fractures and femoral bowing, urogenital abnormalities and a normal karyotype. Early death was identified in 54% of the reported cases, usually due to respiratory complications. The oldest patient at the time of follow up was 10 years of age. Intellectual performance has been variable (developmental testing of our patient at 30 months of age showed a range of developmental skills equivalent to 6 to 11 months of age). Chronic respiratory distress, especially if accompanied by periods of apnea, may be important in the causation of mental retardation. Some patients with the syndrome have normal intelligence, which suggests a normally developing brain, particularly if a craniectomy is performed to treat sutural synostosis and indicates that there may be secondary factors (e.g., apnea) playing a role in the mental retardation (as seen in our patient with a history of apnea) in patients with the Antley-Bixler syndrome. Since choanal atresia/stenosis which diminishes the airway passage is a cardinal feature of this syndrome, choanal stenting should be performed on those patients with this finding during infancy to decrease the airway obstruction. All patients followed beyond infancy were ambulatory, including our patient at 35 months of age, who will take steps with assistance. Although most cases are sporadic, there were reports of recurrence in siblings of both sexes in two families, suggesting an autosomal recessive mode of inheritance. PMID- 7889650 TI - A de novo 6q11-q15 duplication investigated by chromosome painting. AB - A de novo interstitial duplication of the 6q11-q15 chromosome region, confirmed by the application of a chromosome 6 painting probe, was observed in a patient with craniofacial dysmorphism, psychomotor retardation, cryptorchidism and hypospadias. Despite the publication of several cases showing partial trisomy 6q, to our knowledge the duplication of the proximal region q11-q15 has not previously been reported. PMID- 7889651 TI - New allele of probe D17S61 present in the Charcot-Marie-Tooth 1A duplication. PMID- 7889652 TI - Familial mosaic Turner syndrome. PMID- 7889653 TI - Ambral syndrome and congenital generalized hypertrichosis. PMID- 7889655 TI - Analysis of 40 known cystic fibrosis mutations in South African patients. AB - A total of 140 South African (SA) Caucasoid cystic fibrosis (CF) families were analysed for the common CF mutation, delta F508. The 52 non-delta F508 CF chromosomes in a subset of 127 of these families were also tested for 39 other known CF mutations. The most frequent mutation, apart from delta F508 (which occurs at a frequency of 79%), was G542X (1.3%). Four other mutations, R553X, S549N, 621 + 1G-->T and N1303K, were each found in single families. The other 35 mutations remained unidentified in this sample of CF families. Since 83% of SA Caucasoid CF mutations have been identified, diagnosis by mutation analysis will be possible in only 69% of CF cases. When a diagnosis has been confirmed by a positive sweat test, a combination of linked marker analysis and mutation detection will be necessary if prenatal diagnosis and carrier detection are to be offered in the remaining families. PMID- 7889654 TI - Association between genetic variation at the APO AI-CIII-AIV gene cluster and familial combined hyperlipidaemia. AB - By using chemical cleavage mismatch analysis and the single strand conformation polymorphism technique, DNA fragments of the apo CIII gene, including the 5' flanking region and all the exons, were screened for sequence changes underlying the observed association between familial combined hyperlipidaemia (FCHL) and the apo AI-CIII-AIV gene cluster in affected individuals from eight FCHL families. A C1100-T transition in the wobble position of codon 14 in exon 3 and a T3206-G transversion in the non-translated region of exon 4 were identified, occurring in four and all probands, respectively. Using these variants and the G-75-A transition in the apo AI promoter, co-segregation of the gene cluster with hyperlipidaemia could be excluded in all eight families (lod score - infinity at theta = 0). No support for co-segregation was obtained using the affected pedigree member method of linkage analysis (overall T = -0.77 for f(p) = 1 [symbol: see text] p). The frequencies of T1100 and G3206 in a group of 55 patients with combined hyperlipidaemia were 0.35 and 0.52, respectively, which were significantly higher compared to 360 controls (0.21, p < 0.01 and 0.35, p < 0.005 respectively). In patients homozygous for the T1100 allele, levels of plasma triglyceride were 2.5-fold higher (868 mg/dl) than those homozygous for the C1100 allele (337 mg/dl), while patients heterozygous for the polymorphism had intermediate values (443 mg/dl) (p < 0.01). A similar association was seen in controls (p < 0.04). The three polymorphisms studied were in strong linkage disequilibrium in both the group of CHL patients and the unrelated individuals. This study confirms the association between common variation in the gene cluster and differences in plasma lipid levels in the general population and in patients with combined hyperlipidaemia, but fails to confirm co-segregation with FCHL, suggesting the role of other genetic or environmental factors in the aetiology of FCHL. PMID- 7889656 TI - Search for three known mutations in the RYR1 gene in 48 Danish families with malignant hyperthermia. AB - We have examined 48 Danish families in which malignant hyperthermia reactions have occurred, with respect to three of six published mutations in the gene for the calcium release channel of sarcoplasmic reticulum (the RYR1 gene) believed to cause malignant hyperthermia susceptibility in man. The mutations are Arg614Cys, also known as the "pig mutation"; Arg163Cys; and Ile403Met. The only mutation found was Arg163Cys, which was detected in only one family. The results of this study indicate that other mutations must underlie the disorder in most Danish malignant hyperthermia-susceptible families, and that the "pig mutation" is not a frequent cause of malignant hyperthermia susceptibility in Denmark. PMID- 7889657 TI - A cytogenetic register of trisomies in Scotland: results of the first 2 years (1989, 1990). AB - A population-based register of all autosomal trisomies diagnosed in Scotland was established in 1989. Data were provided by all cytogenetic service laboratories, and included karyotype, date and place of outcome, indication for analysis, maternal age and place of residence. The Register includes all foetuses diagnosed prenatally and all cytogenetically-confirmed live- and still-births with autosomal trisomy, including partial, mosaic and familial cases. In the 2 years 1989-90, 76 prenatal and 147 postnatal diagnoses were notified. For Down syndrome karyotypes the estimated rate, assuming no terminations and after adjusting for spontaneous foetal losses following diagnosis, was 1.23 per 1000 livebirths. This was almost identical to that expected by applying published maternal age-specific rates to the maternal age distribution in Scotland, indicating a very high level of ascertainment. The adjusted rates for trisomies 13 and 18 were also close to expected values derived from published data. Prenatal screening was estimated to reduce the newborn incidence of trisomy 21 by about one quarter overall, and about one half in mothers over 35 years. For trisomy 18, the estimated overall reduction was also about one quarter. It is concluded that the Register provides a practical and cost-effective means of monitoring the effects of prenatal screening, with near-complete ascertainment. In the longer term it will provide a database for studies of the aetiology of these conditions. PMID- 7889658 TI - Clinical, ultrastructural and biochemical studies in two sibs with Ehlers-Danlos syndrome type VI-B-like features. AB - Two Turkish sibs with clinical features of Ehlers-Danlos syndrome type VI-B are presented. The hydroxylysine contents of dermis and gel electrophoresis of type I and type III collagen produced by fibroblasts were normal. Ultrastructural studies of skin collagen and elastic fibers showed discrete abnormalities. Other syndromes with similar clinical, biochemical and ultrastructural features are discussed. PMID- 7889659 TI - Partial trisomy of the short arm of chromosome 18 due to inversion duplication and direct duplication. AB - We report one patient with a de novo inversion duplication 18 (pter-->cen) and two cases of direct tandem duplication 18 (pter-->cen), one due to maternal inheritance and the other arising as mosaicism of unknown origin. The duplications are demonstrated by high resolution banding. They were verified by in situ hybridization with a paint specific for chromosome 18 and with DNA probe LI.84 specific for the centromere region of chromosome 18. FISH with the genomic DNA probe pHRR68 specific for 18p11.32 revealed a subtle deletion concomitantly involved in the case of inversion duplication 18p. The patients exhibit slight developmental delay/moderate mental retardation and only a few dysmorphic features. The literature on trisomy 18p is reviewed and the present cases are compared to it. PMID- 7889660 TI - Single mandibular incisor in a patient with del (18p) anomaly. AB - A single mandibular incisor and an unusually narrow mandible and tongue were noted in an 8-year-old moderately retarded boy with 18p- (45, XY, der dic (18) (18qter-p11.2::22p 11.2-qter). While a single maxillary incisor, considered a minor feature of holoprosencephaly, was reported in three cases of 18p-, reduction of mandibular incisors has been a very rare finding and has never been noted in similar cases. PMID- 7889661 TI - No effect on blood pressure level or variability of polymorphisms in DNA at the locus for atrial natriuretic factor (ANF). AB - We have examined healthy Norwegians with respect to two restriction fragment length polymorphisms at the locus for atrial natriuretic factor, detectable with the restriction enzymes XhoI and BglI, respectively. No association with systolic or diastolic blood pressure level or variability was found. Thus, the normal genes detected by examination of these restriction fragment length polymorphisms have neither "level gene" nor "variability gene" effects on normal blood pressure. PMID- 7889662 TI - No effect of a BglI polymorphism at the renin (REN) locus on blood pressure level or variability. AB - We have studied a normal restriction fragment length polymorphism at the renin locus, detected with the restriction enzyme BglI in healthy Norwegians. No association with blood pressure level or variability was found. Thus, the normal genes detected by examination of this restriction fragment length polymorphism at the renin locus have neither "level gene" nor "variability gene" effects on normal blood pressure. PMID- 7889664 TI - Differentiation of congenital hypertrichosis from Ambras syndrome. PMID- 7889663 TI - Chediak-Higashi syndrome with cerebellar cortical atrophy detected by MRI. PMID- 7889665 TI - The effect of topical application of the platelet-activating factor-antagonist, Ro 24-0238, in psoriasis vulgaris--a clinical and immunohistochemical study. AB - Platelet-activating factor (PAF) is considered to be one of the most potent lipid mediators in allergic and inflammatory reactions. Suggestions that PAF is produced by cutaneous cells, and cells infiltrating the skin from the blood, have been reported. PAF has been identified in allergic cutaneous reactions and also in psoriatic lesions. The biological activity of PAF is thought to be mediated by cell membrane receptors. Studies revealed that PAF-antagonists can be active in animal models of cutaneous inflammation. In humans PAF-antagonists showed minimal therapeutic improvement in studies of antigen-induced cutaneous responses in atopic subjects. No data are available on the effects of PAF-antagonists in psoriasis. The objective of this study was to investigate the effect of a potent PAF-antagonist (Ro 24-0238, 10% solution in diethylene glycol monoethyl ether) in 10 patients with chronic plaque psoriasis, a placebo-controlled double-blind study. Clinical response was evaluated and markers of inflammation, differentiation and proliferation were studied immunohistochemically on punch biopsies taken from actively treated and placebo-treated lesions, before and after treatment. This study demonstrated that a 10% solution of the PAF antagonist Ro 24-0238 was not effective at the clinical or cell biological level after a 4-week treatment period. The most likely explanation for these negative observations is that PAF is not a significant factor in the pathogenesis of psoriasis. PMID- 7889667 TI - Relevance of skin phototyping to a Korean population. AB - We have determined skin phototype by a self-reporting questionnaire proposed by Fitzpatrick in 128 Korean medical students. We also measured the minimal erythema dose (MED), minimal melanogenic dose and investigated their relationship to phototype. A questionnaire of skin phototypes revealed that 13.3% of the students are skin phototypes I and II. Based on MEDs, we demonstrated that 14.8% of the students fall into the UV-sensitive group as defined by an MED of less than 40 mJ/cm2, which is the upper range of MED of phototypes I and II in a white population. The skin phototypes did not show a positive correlation to MEDs and only 2.3% of students classified as skin phototypes I and II showed an MED below 40 mJ/cm2. This study indicates that the skin phototyping method proposed by Fitzpatrick does not reliably predict UV-sensitive individuals within the Korean population. PMID- 7889666 TI - Tinea capitis in south Wales--observations in change of causative fungi. AB - We report an observed change in the causative organisms in 45 consecutive cases of tinea capitis seen in the Cardiff area over the last 9 years. Direct microscopy using potassium hydroxide was positive in all but one case, but this was subsequently positive on culture. This retrospective analysis shows that more cases are being seen in our department, and that a higher proportion of cases are due to Trichophyton violaceum whereas previously we would have expected the majority of cases to be due to Microsporum canis. We believe that the change in causative organism that we have identified has important practical and diagnostic implications. Endothrix fungi such as T. violaceum do not fluoresce under Wood's lamp unlike ectothrix fungi such as M. canis, and therefore failure to perform adequate mycological examination of specimens could result in missed diagnoses. We are not aware of this change having been reported from other UK centres. The finding indicates a need for further prospective epidemiological studies to confirm this apparent trend. PMID- 7889668 TI - The efficacy of localized PUVA therapy for chronic hand and foot dermatoses. AB - The response to treatment of all patients enrolled over an 18-month period for localized oral or topical psoralen photochemotherapy (PUVA) of chronic hand and foot dermatoses was retrospectively reviewed. There were broadly similar success rates for the two groups for complete clearance: 61.5% (eight of 13 patients who completed therapy)--oral PUVA, 47.8% (11 of 23 patients who completed therapy)- topical PUVA, and for significant improvement: 23.1% (three of 13 patients)--oral PUVA, 30.4% (seven of 23 patients)--topical PUVA; there were no significant differences in response when diagnostic subgroupings of the hand dermatoses were taken into account. The mean number of treatments (22 for oral PUVA and 24 for topical), treatment durations (122 and 129 days), maximum UVA doses (11.2 and 12.3 J/cm2) and to a lesser extent cumulative UVA doses (189.3 and 237.0 J/cm2) for the therapies were similar in the two groups; adverse effects were minimal for both treatment protocols. However, at least five of the eight patients in the oral PUVA group and five of the 11 in the topical group who cleared completely relapsed after a mean 86 (range 19-245) and 174 (range 23-596) days, respectively. These findings are in broad agreement with those of previous studies. Therefore to avoid generalized photosensitivity and a higher likelihood of adverse effects with systemic therapy, as well as a possible slower relapse rate, topical therapy seems preferable. PMID- 7889669 TI - Agminate Spitz naevi arising on hyperpigmented patches. AB - In 1948 Dr Sophie Spitz described criteria that distinguished juvenile melanoma from malignant melanoma. Since then the cases of eruptive Spitz naevi have been reported arising on normal skin, on lightly pigmented patches and on hypopigmented patches. There are only 12 reports of Spitz naevi arising on hyperpigmented patches: we describe here three further cases, all on the arms of children, seen in our department in a single year. PMID- 7889670 TI - Disaccharide analysis of the skin glycosaminoglycans in patients with Werner's syndrome. AB - The disaccharide content of the chondroitinase-digestible glycosaminoglycans (GAGs) extracted from 6-mm skin punch biopsies from the atrophic and sclerotic skin of two patients with Werner's syndrome (WS) were determined using high performance liquid chromatography after 1-phenyl-3-methyl-5-pyrazolone labelling. The total amount of main disaccharides was significantly decreased in the atrophic lesions of WS. In the atrophic forearm skin, the decrease in the main disaccharide unit of hyaluronic acid, delta Di-HA, and the increase in the ratio of the main disaccharide unit of dermatan sulphate, delta Di-4S, to delta Di-HA were significant vs. normal control (P < 0.01 and 0.05, respectively). The sclerotic skin showed an increase in delta Di-4S (DS) (P < 0.05) and a decrease in delta Di-HA (P < 0.02) compared with normal controls, as well as a significantly higher ratio of delta Di-4S (DS)/delta Di-HA compared with normal controls (P < 0.0002) and systemic sclerosis patients (SSc; P < 0.02). No other statistical difference was found in the amount of each main disaccharide unit between the sclerotic skin of WS and SSc. Histological examination revealed that the atrophic skin showed thinning of the dermis with a slight increase of fine collagen bundles, whereas the sclerotic skin demonstrated a thickened dermis with prominent deposition of fine collagen bundles in the deep dermis. In SSc, thickening of the whole dermis, composed of hyalinized or swollen collagen bundles, was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889671 TI - Dowling-Degos disease associated with Kitamura's reticulate acropigmentation. AB - A family with features of Dowling-Degos disease associated with Kitamura's reticulate acropigmentation is reported. There have been three previous reports describing the association of these two conditions. Our family extends four generations, and the proband shows some unusual features not typical of Dowling Degos disease or Kitamura's reticulate acropigmentation. PMID- 7889672 TI - Pemphigoid nodularis: a report of two cases. AB - Pemphigoid nodularis is a rare variant of bullous pemphigoid characterized by the development of pruritic hyperkeratotic nodules. These nodules may be the presenting feature of the disease, and may precede the development of bullae by several years. The condition appears to be more common in females than males, and is often resistant to treatment. We report two definite cases and one possible case of pemphigoid nodularis, and review the literature relating to this disorder. PMID- 7889673 TI - Cicatricial alopecia occurring in two sisters from Ghana. AB - We report two sisters from Ghana who presented with cicatricial alopecia simultaneously. In both cases the aetiology is unclear although both gave a history of previous scalp folliculitis. We classify the causes of cicatricial alopecia and the difficulties that can arise in placing such patients in a clinical category. Racial origin may be relevant in our cases; to our knowledge this is the first report of cicatricial alopecia occurring in two sisters. PMID- 7889674 TI - Bilateral spectacle frame acanthoma. AB - We report the case of a young white male with bilateral retroauricular spectacle frame acanthoma which developed within a few weeks of wearing ill-fitting sunglasses. Bilateral cases have only rarely been reported. This lesion must be differentiated from malignant proliferative conditions. PMID- 7889675 TI - Chicken pox and acute monocytic leukaemia skin lesions in an HIV-seropositive man. AB - Lymphoid neoplasia is now well known to occur in patients with human immunodeficiency virus (HIV) infection but the first case of acute monocytic leukaemia in an HIV-seropositive man has been only recently described. We report the case of an HIV-infected patient who simultaneously developed skin lesions of acute monocytic leukaemia and chicken pox. We suggest that HIV may produce a malignant transformation of monocytic cells. PMID- 7889676 TI - Erythema nodosum-like eruption in sarcoidosis. AB - Two cases of sarcoidosis with tender, erythematous nodules on the legs are reported. The cutaneous lesions were clinically similar to those of erythema nodosum, but histologically showed non-caseating epithelioid granulomas. A review of 14 cases of this particular sarcoid eruption reported in Japan showed that 13 had ocular involvement as in our cases. In the light of the high frequency of ocular involvement, a skin biopsy should be considered in patients presenting with erythema nodosum-like eruptions situated on the legs. PMID- 7889677 TI - Tufted haemangioma responding to high-dose systemic steroids: a case report and review of the literature. AB - Tufted haemangioma is a rare, acquired vascular tumour most commonly presenting in the first year of life. Some authors consider angioblastoma of Nakagawa and progressive capillary haemangioma to be the same condition, and include them in the lobular capillary haemangioma complex. There have been only a few case reports of tufted angioma in the literature, with little information on effective treatment. We describe a case of tufted angioma presenting in a 3-month-old girl. Because of the tumour's rapid growth, aggressive treatment was felt to be justified. There was no response to interferon alpha-2a but high-dose steroids were commenced with good results. PMID- 7889678 TI - Naevus spilus as a precursor of cutaneous melanoma: report of a case and literature review. AB - Naevus spilus is defined as a melanocytic macule in which there are dark maculopapular speckles. We describe a patient with a superficial spreading malignant melanoma arising in a congenital naevus spilus, and review the literature on this association. PMID- 7889679 TI - Sclerodermatous syndrome after occupational exposure to herbicides--response to systemic steroids. AB - We report a case of generalized cutaneous sclerosis associated with muscle and oesophageal involvement in a patient exposed to herbicides containing bromocil, diuron and aminotriazole. Treatment with oral prednisolone resulted in some improvement in the cutaneous signs, particularly over the face, trunk and proximal limbs. The considerable exposure to chemicals, time course and unusual pattern of organ involvement suggested a diagnosis of occupational scleroderma. PMID- 7889680 TI - A family with pachyonychia congenita affecting the nails only. AB - A family with pachyonychia congenita in which affected individuals showed nail involvement only is described. Pachyonychia congenita is a rare hereditary disorder inherited in an autosomal dominant manner. Various classifications of pachyonychia congenita have been suggested but none indicates nail involvement as a solitary finding. PMID- 7889681 TI - Dermatomyositis associated with malignant melanoma--case report and review of the literature. AB - Dermatomyositis (DM) is a connective tissue disorder characterized by cutaneous and muscle involvement. It is a well recognized paraneoplastic syndrome and has been linked with malignancy in 15-34% of adult patients. The course of DM in such patients usually correlates closely with the activity of the underlying malignancy. We report a patient who developed DM 4 years after excision of a malignant melanoma (MM) from the back and 1 year before the diagnosis of metastatic disease. A literature review revealed that the association of dermatomyositis with MM is rare and consistent with a dismal prognosis. PMID- 7889682 TI - Cicatricial pemphigoid presenting with unusual palmar involvement, successfully treated with a combination of nicotinamide and tetracycline. AB - Cicatricial pemphigoid is a rare subepidermal blistering disease, mainly of elderly women, that primarily involves mucous membranes. Oral, ocular or genital mucous membranes are most frequently involved and skin involvement is less frequent. We report a case of cicatricial pemphigoid with extensive cutaneous involvement, including unusual bilateral palmar involvement. Clinical improvement has been achieved with a combination of topical steroids, oral nicotinamide and tetracycline. PMID- 7889683 TI - A case of the elephant man phenotype with giant rhinophyma and benign symmetric lipomatosis. AB - We described an unusual male patient with two disfiguring diseases, benign symmetric lipomatosis and giant rhinophyma, which gave him a grotesque appearance. His physical appearance had isolated him from the rest of society and was probably the main reason for his alcohol abuse. PMID- 7889684 TI - Circulating macro creatine kinase isoenzyme BB ('macro CK-BB'): a diagnostic pitfall in the interpretation of serum CK concentration. PMID- 7889685 TI - Erosive oral lichen planus due to sensitization to cobalt chloride. PMID- 7889686 TI - Steroid acne with oral prednisolone metasulphobenzoate. PMID- 7889687 TI - Clinical neurological trauma parameters as predictors for neuropsychological recovery and long-term outcome in paediatric closed head injury: a review of the literature. AB - We present a review of recent prospective studies of long-term outcome in paediatric closed head injury. Special attention is given to the relationship between the neurological trauma parameters and neuropsychological outcome. First we discuss the most important methods of assessing the severity of the injury. We review the most prominent neurobehavioural and cognitive sequelae. Subsequently we address the question of prediction of residual sequelae in view of the early trauma parameters. The main problem when comparing different studies is the lack of procedural uniformity both in assessment of the severity of the injury as well as in measurement of neuropsychological outcome. Inconsistencies and discrepancies among various studies are pointed out. We summarise those results which are supported by many studies and hence are less controversial. In addition we present some recommendations for future investigations. PMID- 7889688 TI - Benign extramedullary tumors in the foramen magnum region. AB - We present 16 cases of benign extramedullary tumors of the foramen magnum region who were operated on between the years 1984 and 1992. On admission, no case was neurologically intact and over 50% had had symptoms for more than 1 year. Nine patients had erroneous diagnoses initially. CT myelography and magnetic resonance (MR) imaging were the most appropriate diagnostic tools in visualizing tumors of this region. All operations except one, were performed by the posterior approach without surgical mortality. Histopathological examination revealed 8 meningiomas, 6 neurinomas, one tuberculous abscess and one neurenteric cyst which has not been reported at this location before. Patients with minor to moderate disability on admission showed good functional results without any recurrences during follow up. PMID- 7889689 TI - Microvascular decompression for trigeminal neuralgia: a critical reappraisal. AB - The results of posterior fossa explorations for trigeminal neuralgia over the period 1980-1990 in 58 patients and in 59 procedures were studied retrospectively. In 51 procedures vascular compression was treated by microvascular decompression (MVD). In the absence of such a compression, partial sensory rhizotomy (PSR) was performed in 5 cases and only adhesiolysis of thickened arachnoidea in 2 cases. In one additional case the procedure was terminated prematurely due to the development of cerebellar edema. Two months postoperatively a good or fair result was obtained in 80% of the procedures. At long-term follow-up (mean 77.3 months, range 8-146 months), a good or fair result was maintained in 71%. There was no significant difference in outcome between the MVD group and the other procedures, or between the three groups formed according to the type of vascular compression. However, in the group of 10 patients with a history of a procedure affecting the trigeminal ganglion or nerve root the result was worse. In the group of 41 MVD patients rendered free of pain at 2 months postoperatively, 8 patients perceived a recurrence. The annual recurrence rate was calculated to be 2.6%. There was no mortality in this series but the morbidity rate was 22% including 1.7% persistent neurological deficit. Compared to the literature results of percutaneous controlled differential thermocoagulation (PCDT), the recurrence and failure rates in the present series appear to be more or less the same. As neither of the two is an unequivocally more effective treatment, we are of the opinion that the less invasive procedure should be preferred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889690 TI - Phenytoin parahydroxylation is not impaired in patients with young-onset Parkinson's disease. AB - Impaired hepatic detoxification capacity by cytochrome P450 subsystems has been implicated in the pathogenesis of Parkinson's disease. We have demonstrated that hepatic parahydroxylation of phenytoin (PHT) is impaired in patients with late onset Parkinson's disease. In the present study, we have investigated the hypothesis that PHT parahydroxylation is even more impaired in patients with young-onset Parkinson's disease (age at onset before 40 years). We determined PHT parahydroxylation capacity in 21 patients with young-onset Parkinson's disease and 15 healthy age-matched controls. PHT parahydroxylation capacity was assessed by measuring the ratio of PHT to its major metabolite p-hydroxyphenyl phenylhydantoin in serum 6 h after an oral test dose of 300 mg PHT. PHT parahydroxylation did not differ significantly between patients and controls. These results argue against the hypothesis that impaired activity of the cytochrome P450 isoenzyme responsible for PHT parahydroxylation is involved in the etiology of Parkinson's disease. PMID- 7889691 TI - Tumor necrosis factor and interleukin-6 in critical illness polyneuromyopathy. AB - Critical illness polyneuromyopathy (CIPN) occurs in critically ill patients on artificial respiration. The pathophysiology of this disease is unknown. Because of the strong association with sepsis, the levels of cytokines, TNF and IL-6 were measured several times daily in patients having CIPN and in a control group of critically ill patients without CIPN. The diagnosis of CIPN was made on clinical criteria. Patients with CIPN had no significantly elevated levels of TNF or IL-6 as compared to controls. PMID- 7889692 TI - Different types of plasminogen activator activity in human brain tumours: relation with peritumoral oedema? AB - In 20 tissue samples from human brain tumours the concentrations were measured of (1) total plasminogen activator activity, (2) tissue-type plasminogen activator (t-PA) activity, (3) urokinase-type plasminogen activator (u-PA) activity, and (4) t-PA antigen. Most tumours contained a considerable amount of t-PA, but a high interindividual and in a few cases even an intra-individual variability was observed. A weak but significant negative correlation was found between t-PA concentration and the oedema/tumour ratio, as calculated from the preoperative computerized tomography (CT) brain scanning. No correlation was found with u-PA activity. It is concluded that t-PA and u-PA are probably not important factors in the production of peritumoral cerebral oedema, but a correlation between locally different amounts of t-PA or u-PA and the locally different extent of surrounding oedema has not yet been excluded. PMID- 7889693 TI - Sneddon's syndrome: clinical and immunohistochemical findings. AB - Results of immunological studies on skin biopsies of 5 patients with Sneddon's syndrome are reported. Also studied were coagulation factors and autoantibodies believed to play a role in this syndrome. Hemostasis was normal except for a mild increase of fibrinogen in one subject; lupus anticoagulant (LAC) and anticardiolipin antibodies were negative in all. The skin biopsies ruled out systemic vasculitis and vasculitis in association with connective tissue diseases. Sneddon's syndrome is a peculiar clinicopathological condition, probably with several etiologies, but is distinct from primary antiphospholipid syndrome. PMID- 7889694 TI - Nonconvulsive status epilepticus in patients with cancer. AB - Patients with systemic cancer may have altered mental status without evidence of metastases, strokes, or metabolic encephalopathies. Six such patients are described whose EEGs showed continuous generalized epileptiform discharges in the absence of clinical signs of seizures. Two patients had never had any clinical evidence of seizures, and four had seizures that were thought to have stopped before the EEG. Three patients were confused, and three were stuporous or comatose. In some patients the nonconvulsive epileptic activity may have been directly related to the cancer; three had findings suggestive of possible paraneoplastic encephalopathies. Anticonvulsants led to an improved mental status in four patients, but all except one died. Nonconvulsive generalized status epilepticus may explain altered mental status in some patients with cancer, and anticonvulsant medication treatment can be beneficial. PMID- 7889695 TI - Occult cerebrovascular malformations: 2 cases. AB - Since the introduction of high accuracy CT scanning and MR imaging, angiographically occult cerebrovascular malformations are a relatively common finding. The clinical presentation is usually related to hemorrhage. Asymptomatic intralesional bleeding frequently occurs. Currently, MR imaging is the most sensitive method for the detection of occult cerebrovascular malformations. The dynamic nature of these malformations seems to be a key factor in their therapeutic management. We present 2 cases of occult cerebrovascular malformations and discuss the clinical presentation, neuroradiologic appearance and current management of these lesions. PMID- 7889696 TI - The pathogenesis of syringomyelia in spinal cord ependymoma. AB - A spinal cord ependymoma with syringomyelia is presented. The pathogenesis of syrinx formation, associated with intramedullary tumors is not fully understood. In order to examine the mechanism of formation of the tumor-associated syrinx, syrinx fluid was obtained during surgery and concentrations of proteins were measured in the syrinx fluid, the cerebrospinal fluid (CSF) and blood serum. Protein analysis of fluid specimens showed the fluid in tumor-associated syrinx to be an exudate. This strongly indicates that, in this case, intramedullary tumor-associated syringomyelia is based on disruption of the blood-brain barrier. PMID- 7889697 TI - Corticosteroid-responsive parkinsonism associated with primary Sjogren's syndrome. AB - A 74-year-old woman with primary Sjogren's syndrome confirmed by salivary gland biopsy presented with parkinsonism. Magnetic resonance imaging (MRI) of the brain revealed multiple small high intensity lesions in the deep white matter, basal ganglia and pons on T2-weighted images. Treatment with L-dopa failed to improve the parkinsonian features. After the initiation of prednisolone 30 mg/day, the parkinsonian signs and symptoms significantly improved. Some lesions on MRI were decreased in size after corticosteroid therapy. These findings suggest that parkinsonism associated with primary Sjogren's syndrome is at least in part attributable to small vessel vasculopathy such as focal inflammation or edema. PMID- 7889698 TI - Amyloid and peripheral nervous system disease. PMID- 7889699 TI - Central nervous system tuberculoma. PMID- 7889700 TI - Patients' perceptions of magnetic resonance imaging. AB - There are several anxiety-related reactions associated with magnetic resonance imaging (MRI). Patients who experience such reactions may disrupt the examination or move so much that images are degraded. These experiences may also influence patients' perceptions of the quality of their care. The objective of this study was to further assess the subjective experiences of patients undergoing MRI in an attempt to identify those patients likely to have problems and factors affecting their experiences. Five hundred consecutive patients undergoing MRI were surveyed using questionnaires before and immediately after imaging. Anxiety was measured using the state anxiety component of the state-trait anxiety inventory. All patients exhibited some degree of pre-imaging anxiety. This was particularly associated with a previous 'unpleasant' imaging experience. Patients who experienced problems during MRI had pre-imaging anxiety levels equivalent to patients about to undergo surgery, were more likely to react badly when first seeing the scanner and were more likely to leave the MRI unit with even greater feelings of anxiety than when they arrived. In contrast to previous studies, anxiety was not associated with either the patient's understanding of the procedure or the duration of the examination. Several features have been identified which could improve the patient's experience (e.g. better information sheet). Awareness of MRI-related anxiety should also be considered when assessing the impact of MRI on outcome for the patient. PMID- 7889702 TI - Fine needle aspiration in infected hip replacements. AB - Ninety painful prosthetic hips from 88 consecutive patients underwent fine needle aspiration and the results compared with clinical progress, operative findings and culture. Fourteen of the 15 cases proven to be infected at operation were correctly identified by fine-needle aspiration. The one hip with a false negative aspirate had an arthrogram which showed a cavity suggesting infection. There were three false positive aspirates. One grew a different organism at surgery from the original aspirate. The other two had no growth on surgical culture. Both had had pre-operative antibiotics. Eleven cultures of doubtful significance were repeated or regarded as negative and the patients carefully followed-up. One repeat culture confirmed infection emphasizing the importance of repeating doubtful aspirates. The sensitivity of aspiration is 93%, specificity is 96%. The accuracy is 95% confirming that aspiration is a simple and reliable method of diagnosing infection in hip prostheses. PMID- 7889701 TI - Normal variations of the temporal bone on high-resolution CT: their incidence and clinical significance. AB - We evaluated normal variations of the temporal bone on high-resolution computed tomograms (HR-CTs) and investigated their incidence. HR-CTs of the temporal bones of 325 patients were retrospectively reviewed. Six groups of variants, which were considered important for presurgical planning, were evaluated on HR-CTs. These included: (1) an incomplete bony covering of a high-positioned jugular bulb; (2) severe asymmetry of the jugular foramen; (3) an anteriorly located sigmoid sinus; (4) a deep sinus tympani; (5) a large internal auditory canal; and (6) a large cochlear aqueduct. The frequency of the variations were as follows: (1) 2.4%; (2) 4.0%; (3) 1.6%; (4) 5.9%; (5) 2.3%; and (6) 3.0%. Bilateral involvement with variation (4), (5) and (6) was frequently seen. Normal anatomical variations of the temporal bone are therefore not rare and awareness of the possible variants is necessary before surgery of the inner ear, middle ear and posterior fossa. PMID- 7889703 TI - Clostridium difficile colitis: correlation of CT findings with severity of clinical disease. AB - Clinical records and abdominal CT scans from 64 patients with documented Clostridium difficile disease were reviewed to determine if any correlation existed between CT findings of colitis and severity of clinical disease. Clostridium difficile disease was documented with stool toxin titre levels and CT scans were performed within 3 days of stool sample. Clinical disease severity was estimated by tabulating the degree of fever, WBC count, frequency and duration of diarrhoea. Thirty-nine of 64 patients showed CT evidence of colitis of which 28/39 showed evidence of focal colitis and 11/39 had pancolitis. CT findings suggesting colitis included colonic wall thickening (39 patients), nodular mucosal thickening (11 patients), the 'accordion pattern' (3 patients), pericolonic oedema (27 patients) and ascites (10 patients). Twenty-five of 64 patients showed no CT evidence of colitis. The clinical severity of disease did not statistically differ (P < 0.05) between patients with CT evidence of colitis and those without colitis. The only CT finding that correlated with clinical severity of disease was nodular mucosal thickening which was found with significantly (P < 0.05) more frequency in patients with a WBC count > 11,000 mm3. CT changes with Cl. difficile disease correlate poorly with the clinical severity. This and negative findings do not exclude the disease. PMID- 7889704 TI - A continuing role for pre-operative cervical spine radiography in rheumatoid arthritis? AB - Pre-operative cervical spine radiographs are routinely requested for patients with rheumatoid disease, prior to elective orthopaedic surgery, but no guidelines exist governing the indications for this investigation. One hundred and twenty eight such patients were reviewed retrospectively. No patient had signs or symptoms attributable to cervical cord compression. The incidence of unsuspected C1/2 subluxation was 5.5%, and as many as 37% of examinations could have been avoided by assessing previous radiographs. The apparent lack of effect on subsequent anaesthetic management was noticeable. Techniques that do not require hyperextension of the neck were employed in 12 of 19 patients with craniocervical instability and included the laryngeal mask airway, face mask or spinal anaesthesia. However, similar variations in anaesthetic technique were observed in patients without cranio-cervical instability. It is concluded that pre operative cervical spine assessment in asymptomatic patients with rheumatoid disease is unnecessary, prior to elective orthopaedic surgery. PMID- 7889705 TI - Buscopan and glaucoma: a survey of current practice. AB - Hyoscine butylbromide (Buscopan) is commonly used by radiologists in the UK as a hypotonic agent in double-contract gastrointestinal studies. A history of glaucoma is still taught to be the prime contraindication to its use, although the only individuals at risk are those with undiagnosed and therefore untreated angle closure glaucoma (ACG), who will not give a positive history. We conducted a postal survey of all members and fellows of the Royal College of Radiologists in the UK to establish current practice. RESULTS: Of the 1045 respondents who use Buscopan, 724 (81.6%) withhold it if the patient gives a history of glaucoma, and 631 (87.2%) of this group substitute glucagon. Of the 51 respondents who state that they understand that the patient who gives the positive history is not the one at risk, 22 continue to withhold Buscopan because of the established teaching. Only 429 (52.4%) substitute glucagon for Buscopan if the patient gives a history of heart disease. Eight respondents (0.8%) have seen an attack of glaucoma thought to have been precipitated by Buscopan, and 20 (1.9%) have seen cardiac complications. CONCLUSION: There are still widespread misconceptions about the contraindications to the use of Buscopan among radiologists in the UK. We recommend abandoning the practice of enquiring about a history of glaucoma, and substituting advice to seek urgent medical advice should eye pain and visual loss develop. Caution in the patient with heart disease appears to be of greater importance. PMID- 7889706 TI - Sclerosing lymphocytic lobulitis of the breast. AB - Eight patients are described who had palpable breast lumps with clinical and imaging features suspicious of malignancy which proved to be sclerosing lymphocytic lobulitis on histological examination. In this series the typical mammographic appearance of this condition was increased parenchymal density and/or localized stromal distortion while on ultrasound, the typical appearance was an ill-defined mass with distal acoustic shadowing. This rare benign condition has been described in association with longstanding insulin-dependent diabetes or autoimmune disease, but four of our eight patients had no such medical history. PMID- 7889707 TI - Direct and indirect MRI findings in ganglion cysts of the common peroneal nerve. AB - MRI findings in three cases of ganglion cyst of the common peroneal nerve are presented. In each case the cyst was imaged as an oval structure in transverse section section adjacent to the fibular neck. The cyst extended in a tubular fashion over several slices with an inferior extension towards the superior tibiofibular joint. Signal intensity was intermediate on T1- and high on T2 weighted images. In addition, increased signal on both T1- and T2-weighted images was noted throughout the peroneal compartment and was associated with clinical and EMG evidence of denervation. This has not been previously described but may be an important indirect sign which, when seen, should prompt a careful search in the region of the fibular neck for an underlying ganglion cyst of the common peroneal nerve. PMID- 7889708 TI - Ultrasound of Kimura's disease. AB - Kimura's disease is found almost exclusively in Orientals. It commonly affects the head and neck region and mainly involves the major salivary glands and regional lymph nodes. Its appearances can be mistaken for malignant disease. We present two patients with Kimura's disease. In one patient the disease involved the soft tissues and parotid gland, and in another the submandibular gland. Both patients demonstrated lymphadenopathy in the submandibular, submental areas and upper cervical region. Both patients had ultrasound examination of the salivary glands and neck. One of the patients also had contrast-enhanced CT and MRI. The clinical, pathological and imaging findings of Kimura's disease are discussed. PMID- 7889709 TI - Congenital anomalies of the portal venous system--CT appearances with embryological considerations. AB - The portal vein is formed by the union of the splenic and superior mesenteric veins behind the neck of the pancreas. This system is derived from the vitelline veins, a component of the extraembryonic venous system. In this paper we report three cases, each of which illustrates a congenital variant of the portal venous system, describe their computed tomography appearances and discuss the embryological processes accounting for these anomalies. PMID- 7889710 TI - Ileal loop conduit volvulus: a rare but reversible cause of bilateral ureteric obstruction. AB - Conduit volvulus is a very rare complication of ileal loop diversion. To date it has not been described in association with parastomal herniae. We report two such cases. Antegrade nephrostogram established the diagnosis and nephrostomy drainage facilitated spontaneous resolution of the volvulus with return to baseline renal function in both patients. Percutaneous drainage was the only intervention required in one case. For the second patient, percutaneous decompression permitted elective surgical refashioning of the conduit following clinical stabilization. Conduit volvulus in association with a parastomal hernia is a potentially reversible cause of renal impairment in patients with urinary diversions. The diagnosis depends on accurate radiological evaluation. The initial treatment of choice is percutaneous drainage with elective surgery when the patient's clinical status has improved. PMID- 7889711 TI - A Mars bar is not an adequate fatty meal--a comparison with Calogen. AB - A prospective study was performed to compare the contractility of the gall bladder ultrasonically after ingestion of a 65 g Mars bar or 60 ml of Calogen. Using a repeated measure design, 27 healthy subjects were studied fasting and at 10 min intervals after ingestion of the fatty meal. Results show that there is a significant difference between Mars bar and Calogen (ANOVA, P < or = 0.01), with Calogen producing greater gall bladder contraction overall, and that the ejection fraction is greatest at 40 min (t = 2.23, P < or = 0.01). It is suggested that 60 ml of Calogen is used as the standard fatty meal to assess gall bladder contractility and that the patient is rescanned 40 min post fatty meal. PMID- 7889712 TI - Pictorial review: CT appearances of contrast medium extravasations associated with injury sustained from blunt abdominal trauma. AB - Contrast-enhanced CT is a valuable imaging modality in detecting extravasation of intravascular, urinary tract of gastrointestinal contrast medium in major blunt trauma victims. This pictorial review illustrates the CT appearance associated with extravasation of contrast medium from these various sites and emphasizes features that differentiate among them. PMID- 7889713 TI - Case report: short tau inversion recovery (STIR) sequence MRI appearances of reflex sympathetic dystrophy. PMID- 7889714 TI - Case report: parathyroid carcinoma uptaking pertechnetate but not thallium--a serious potential pitfall. PMID- 7889715 TI - Case report: diagnosis of fetal vesicoureteric reflux as the cause of pelvicalyceal dilatation on antenatal ultrasound. PMID- 7889716 TI - Case report: primary high grade surface osteosarcoma. PMID- 7889717 TI - An unusual cause of MRI artefact. PMID- 7889718 TI - Corticosteroid prophylaxis in patients at increased risk of adverse reactions to intravascular contrast agents. PMID- 7889719 TI - Aortocaval fistulae presenting with renal failure. PMID- 7889720 TI - Common iliac artery arising from the renal artery. PMID- 7889721 TI - [Obesity: a multifactorial disorder with difficult long-term treatment]. AB - Obesity is a social disease and amounts to a real medical problem. After considering its epidemiology, the authors discuss diagnostic methods, etiopathogenesis, clinical features, complications, and management of obesity. Special stress is laid upon particular problems concerning the causes of obesity which are often difficult to identify, and difficulties of long-term treatment. Thus it becomes obvious that the disorder must be prevented, and maximum attention must be placed on renewed weight increase. PMID- 7889722 TI - [Hydrogels in medicine. Origin and clinical use]. AB - Hydrogels are a new revolutionary method used to dress wounds without using gauzes and cotton wool. Our hydrogels were produced by irradiation and are perfectly sterile and biocompatible. The innovation of this topical treatment permits direct contact of hydrogels on wounds and results in complete repair of wounds and ulcers that do not heal easily. The fundamental advantage are: disappearance of local pain, very good protection of wounds, easy removal of necrotic tissue, total adhesion on wounds and simple removal without pain, faster tissue repair. PMID- 7889723 TI - [Therapy of arterial hypertension associated with acute stroke. Current trends and problems]. AB - Acute stroke may cause hypertension and actually available devices for non invasive blood pressure monitoring make it possible to study short-term variability of pressure in this condition, in order to settle a more rational diagnostic and therapeutic approach. In our experience blood pressure variability has shown to be greater in thrombo-embolic, than haemorrhagic stroke. This outcome contributes to explain literature disagreement on benefits of antihypertensive therapy and suggests the need for blood pressure monitoring in every trial, that wants to evaluate with satisfactory reliability the antihypertensive treatment in ischaemic stroke. As to antihypertensive drugs to be used in stroke patients, we prefer antiadrenergics, because hypertension in this clinical condition is due to adrenergic overactivity. Our preliminary experience with a centrally acting antiadrenergic drug (clonidine) has shown its ability not only to reduce blood pressure, but also blood pressure variability in ischaemic stroke. PMID- 7889724 TI - [Role of magnetic resonance in identification of biliary pathology. Comparison with other imaging techniques]. AB - We discuss in this paper the possibilities and limits of MR imaging in the evaluation of the biliary tree and its pathological aspects. We conclude that morphological aspects are the most important markers for differential diagnosis. Actually, signal intensity is not thought to be a decisive finding for differential diagnosis. PMID- 7889725 TI - [Preoperative treatment with GnRH analogs in hysterectomy]. AB - The authors discuss the usefulness of GnRH analogues inducing, through pituitary desensitization, a transient block of gonadal steroidogenesis--before hysterectomy for uterine leiomyomas. In patients with severe anemia these drugs proved to be very effective in improving the haematologic parameters; they also cause a significant reduction of uterine volume, thus allowing, in selected cases, vaginal hysterectomy in selected cases. PMID- 7889726 TI - [Metabolic emergencies in oncology: the tumor lysis syndrome]. PMID- 7889727 TI - [Study PROTECT (Perindopril Regression of Vascular Thickening). European Community Trial]. PMID- 7889728 TI - Evaluation of different vaccines to control of pig colibacillosis under large scale farm conditions. AB - The aim of the study was to evaluate, under large-scale farm conditions, the prophylactic effect of various inactivated E. coli vaccines in the control of pig colibacillosis. The investigations were carried out with 2472 pregnant sows, immunized with 8 different vaccines containing E. coli fimbrial adhesins and adjuvants. Efficacy of the biologicals used was tested by evaluation of the health state of the newborn piglets, i.e. number of born and weaned piglets, percentage of piglets with diarrhea and dead piglets, and mean body weight gain of weaned piglets. It was also intended to check the influence of immunization on the number of pathogenic E. coli strains in the faeces of piglets originating from the vaccinated sows. The vaccines used in the study differed in their protective effect but all of them had a positive influence on the health status of the newborn piglets as well as on the reduction in the faeces of the number of pathogenic E. coli isolates. The best results were obtained when pregnant sows were immunized with a vaccine containing purified K88, K99, and 987P fimbriae and B subunit of LT enterotoxin. It seems that the determination of the number of pathogenic E. coli strains in the faeces of piglets originated from dams vaccinated against colibacillosis can be helpful in the evaluation of the vaccine efficacy. PMID- 7889729 TI - Detection of aerolysin gene in Aeromonas strains isolated from drinking water, fish and foods by the polymerase chain reaction. AB - A polymerase chain reaction (PCR) technique was used to assay the presence of the aerolysin gene in a total of 89 Aeromonas hydrophila and A. sobria strains isolated from drinking water, fish and foods. These strains were also characterized for the production of virulence factors such as haemolysin, protease and cytotoxin. The primers used in the PCR targeted a 209-bp fragment of the aer gene coding for the beta-haemolysin and detected template DNA only in haemolytic A. hydrophila strains. The cell-free culture supernatants of these aerolysin-positive A. hydrophila strains were also cytotoxic to the HeLa and McCoy cells. The haemolytic A. sobria and non-haemolytic A. hydrophila were consistently negative in the PCR assay. Primer specificity was determined in the PCR by using a control haemolytic Escherichia coli, Streptococcus pyogenes and a restriction endonuclease assay. The PCR clearly identified the aerolysin producing strains of A. hydrophila and may have application as a rapid species specific virulence test. PMID- 7889730 TI - Systemic and mucosal intestinal antibody response of sheep immunized with aromatic-dependent live or killed Salmonella typhimurium. AB - Following the development of a suitable formulation capable of inhibiting intestinal proteolytic activity, the total anti-lipopolysaccharide (LPS) and anti flagellin (Fla) antibody response and isotype in the sera and intestinal washings of sheep, immunized with live aromatic-dependent (aro-) Salmonella typhimurium strain CS332 by the intramuscular (live i.m.) or oral (live oral) route or acetone-killed virulent S. typhimurium by the intramuscular route (killed i.m.), were determined at various intervals post-immunization. The serum or intestinal anti-lipopolysaccharide (LPS) or anti-flagellin (Fla) antibody titres of immunized sheep, regardless of the route of immunization, were significantly greater (P < 0.01) than those of non-immune control sheep. Although significant differences between the serum anti-LPS or anti-Fla antibody titres of sheep in various immunization regimes were observed, they were not consistent for different periods post-immunization. The predominant isotype contributing to serum anti-LPS antibody activity was IgM whereas the serum antiflagellar antibody activity was confined to IgM, IgG1 and IgG2. In either case, the contribution of the IgA antibody isotype was minimal. Antibody activity in the intestinal washings of immunized sheep, regardless of the route of immunization was significantly greater (P < 0.01) than that in non-immune control sheep. However, the titres in sheep immunized with the live S. typhimurium vaccines were significantly greater than those immunized with the killed vaccine. The major anti-LPS or anti-flagellin antibody isotype in the intestinal washings of sheep in the live i.m. or live oral groups was IgM at day 7 post-immunization followed by IgG1 and IgG2 at days 14 and 21 post-immunization, with only a minimal contribution by the IgA antibody isotype. On the other hand, the major antibody isotype in the intestinal washings of sheep immunized with the killed S. typhimurium was IgG1. PMID- 7889731 TI - Effect of chemical sympathectomy on the neural spread of pseudorabies virus in mice. AB - To investigate the routes of neural spread of pseudorabies (Aujeszky's disease) virus (PRV), the effects of chemical sympathectomy by 6-hydroxydopamine (6-OHDA) on clinical signs and viral spread in mice inoculated intraocularly with PRV were examined. Similar to non-treated mice, the treated mice developed pruritus as a major clinical sign, followed by peracute death, but the time of death tended to be slightly delayed in about half of the treated mice. On immunohistological examination, viral antigens in treated mice were found to be markedly reduced in all the ipsilateral retinae; they were detected diffusely in the forebrain area with a localization in the mammillary area. In the treated mice, viral antigens were also reduced in the ipsilateral trigeminal nerve ganglia as well as in its central nuclei. These findings indicate that both the sympathetic nervous system and the trigeminal nervous system play an important role in the neural spread of PRV. Possible involvement of the dopaminergic nervous system, particularly in the eye, as the main site of viral growth was discussed. PMID- 7889732 TI - Antigenic heterogeneity of N2 neuraminidases of avian influenza viruses isolated in Israel. AB - Twenty one N2 neuraminidase (NA)-containing viruses isolated in Israel from different avian hosts during 1971-1984 were studied comparatively by means of the panel of 7 monoclonal antibodies (MAB) against A/Guiyang/57(H2N2) virus. Fifteen from the 21 viruses were studied in comprehensive cross reaction NA inhibition (NI) tests with the corresponding polyclonal antisera. The principal result of the studies is that all the isolates can be distributed into two main groups. The 1st group includes the majority of the isolates whose NA shows close relatedness to the "early" (1957 type) N2 NA by NI tests with polyclonal antisera, and demonstrates remarkable stability in the NI tests by reacting with the same 6 from 7 MABs of the panel. The 2nd group does not show any special kinship to either "early" or "late" (1968 type) N2 when analyzed with polyclonal antisera and demonstrates heterogeneity by the analysis with the MABs. A hypothetical explanation of the phenomenon of co-circulation in the local avian reservoir of viral strains displaying either remarkable stability or wide heterogeneity of their NAs is suggested. In accordance with it, the viruses with "stable" ("conservative") N2 NA did not leave the avian reservoir and, hence, did not drift because of very low antibody "selection pressure". Contrary to it, the viruses with heterogeneous N2 NA had been circulating in the human (mammalian) reservoir during various periods before their transfer into the avian reservoir; they drifted accordingly and, being then isolated from birds and designated as "avian" viruses, demonstrate heterogeneity of their NAs which is typical for human viruses. PMID- 7889733 TI - Fatal disease mimicking leptospirosis in a dog, caused by Aeromonas hydrophila. AB - A dog was treated for leptospirosis on clinical and epidemiological arguments. The amoxicillin treatment was not successful. Pure culture of Aeromonas hydrophila was then obtained from liver and kidney, indicating that the septicemia was due to this bacteria commonly found in waters. PMID- 7889734 TI - A note on the concurrent isolation, from horses and ponies, of influenza A/EQ-1 and A/EQ-2 viruses from an epidemic of equine influenza in India. AB - A/eq-1 and A/eq-2 influenza viruses were isolated simultaneously from an epidemic of equine influenza in north India. Evidently, both types of equine influenza viruses circulated in the equine population at the same time. PMID- 7889735 TI - Intestinal immune response induced in mice by staphylococcal enterotoxin B. AB - To investigate the induction of intestinal immunity to staphylococcal enterotoxins (SE) we have chosen the mouse as an experimental model. Since this species is devoid of emetic mechanism, SE can be administered orally without any loss. Mice were treated orally and/or parenterally with staphylococcal enterotoxin B (SEB). The anti-SEB response, either in serum or in the supernatant of in vitro cultured intestinal fragments was determined by enzyme immunoassay (EIA). The results showed that orally given SEB induced specific antibodies both in serum and intestinal secretions. Compared to oral route alone, parenteral followed by oral administration of SEB induced a higher intestinal response with IgA as predominant isotype. Although these results cannot directly be extrapolated to humans or animals with emetic reaction to SE, they do show the implication of intestinal immune system in response to this group of toxins. PMID- 7889736 TI - The definition of a general practice medical workstation: the ISAAC approach. AB - Within the principal objective of ISAAC of developing information technology support for the General Practice, the project aims at the definition of a Global Architecture valid for GPs all around Europe. This is achieved with the definition of a Functional Reference Model describing GP's functions. Professionals from the Primary Health Care (PHC) area are extensively involved in the project. Prototypes have been and will be defined to test the project approach in real life conditions. The prototypes test the usability of a local information processing environment and the integration with other components of the Health Care System. PMID- 7889737 TI - KAVAS-2: Knowledge Acquisition, Visualization and Assessment System. AB - The objective of KAVAS-2 is the development of a tool, named KAVIAR, with which domain experts can make their knowledge explicit. It contains components for (computer assisted) knowledge elicitation and for machine learning. A key issue in KAVAS is the assessment of the quality of the classification and domain models built. Various quality measures are available and implemented in KAVIAR to assess the quality of models, specifically those developed from data bases by machine learning techniques. PMID- 7889738 TI - AIM Project A2002: CAMARC-II (computer aided movement analysis in a rehabilitation context-II). AB - CAMARC-II intends to establish a European network of clinical and research centres, interconnected with the manufacturers of the relevant instrumentation and with 'end-users' like insurance companies, which will allow a standardised approach to the Functional Assessment (FA) of the motor (dis)ability of the motor impaired and/or the elderly. The objectives of the project are: to build-up a Europe-wide network to practice Movement Analysis; to define agreed clinical and experimental protocols; to integrate existing and new instrumentation; to define suitable User Interfaces driving the clinician in the tests; to define a comprehensive Knowledge Base (KB) of the MA experience: to build-up suitable databases (DB) of MA data accessible through the Network; to assess criteria for the definition of normative data for a conventional age-related classification of normality, impairment and disability for the motor behaviour. A number of achievements are mentioned in the paper. PMID- 7889739 TI - Biomagnetic methodologies for the noninvasive investigations of the human brain (MAGNOBRAIN). AB - Magnetoencephalography (MEG) non-invasively infers the distribution of electric currents in the brain by measuring the magnetic fields they induce. Its superb spatial and temporal resolution provides a solid basis for the 'functional imaging' of the brain provided it is integrated with other brain imaging techniques. MAGNOBRAIN is an applied research project that developed tools to integrate MEG with MRI and EEG. These include: (1) software for MEG oriented MRI feature extraction; (2) the Brain Data Base (BDB) which is a reference library of information on the brain used for more realistic and biologically meaningful functional localisations through MEG and EEG; and (3) a database of normative data (age and sex matched) for the interpretation of MEG. It is expected that these tools will evolve into a medical informatics environment that will aid the planning of neurosurgical operations as well as contribute to the exploration of mental function including the study of perception and cognition. PMID- 7889740 TI - MARGOT: medical archive generation with object-oriented techniques. PMID- 7889741 TI - MENELAS: an access system for medical records using natural language. AB - The overall goal of MENELAS is to provide better access to the information contained in natural language patient discharge summaries, through the design and implementation of a pilot system able to access medical reports through natural languages. A first, experimental version of the MENELAS indexing prototype for French has been assembled. Its function is to encode free text PDSs into both an internal representation and ICD-9-CM nomenclature codes. A preliminary evaluation shows the potential for reasonable coverage and precision. The MENELAS prototype will be enhanced and extended into a pilot system which will be tested in two hospital sites. PMID- 7889742 TI - METROPOLIS: telecommunications services for health care added value (strategies for telematics systems in metropolitan areas to improve health care delivery. PMID- 7889743 TI - MILORD: Multi-media Interaction with Large Object-oriented Radiological and clinical Databases. AB - The MILORD project concerns the storage, communication, and processing of large multi-media clinical information in an integrated environment. Advanced information technologies are exploited: new knowledge representation languages and tools, friendly human-computer interaction, 3D graphical processing and displaying of medical images, high performance parallel architectures, large scale distributed data storage, federated environments for clinical cooperation. The project is developing an environment for designing and handling medical workstations. New turn-key marketable systems are expected after the end of the project. From its first version, the system is installed and under evaluation in large hospitals. PMID- 7889744 TI - Structuring the patient record: NUCLEUS (customisation environment for multi media integrated patient records). AB - The NUCLEUS project (AIM A2025) develops a prototype of a multi-media integrated patient record, based on the concepts of intelligent act management as conceived in RICHE (Esprit 2221). Moreover, NUCLEUS creates facilities for the customisation of such patient record according to the requirements of the health professionals (physicians, nurses, therapists, etc.) who operate and consult the patient record. Health professionals retain full control of the patient record contents:--NUCLEUS offers facilities to structure any significant patient record, subject to the specifications of the health professionals involved. Finally, NUCLEUS implements its results in the practical clinical conditions of the three leading European hospitals. PMID- 7889745 TI - OPADE: optimization of drug prescription using advanced informatics. AB - The computerized drug prescription system (CDPS) is an old, almost obsolete, dream, and numerous researchers have developed prototypes or even full fledged packages. But few systems are currently used in clinical practice. The OPADE project, presented in this paper, aims at developing a computerized system which allows for optimization of drug prescription from a medical, patient compliance and economical point of view; the system will be adapted to different European countries, integrated and customized to local medical practice so as to insure user acceptance. PMID- 7889746 TI - OpenLabs: the application of advanced informatics and telematics for optimization of clinical laboratory services. AB - OpenLabs has four major objectives: to improve the efficiency and effectiveness of clinical laboratory services by the integration of Knowledge Based Systems (KBSs) with Laboratory Information Systems (LISs) and equipment; to provide and implement standard solutions for Electronic Data Interchange (EDI) between laboratories and other medical systems; to specify a fully Open architecture for an integrated Clinical LIS and demonstrate the integration of various KBS modules on the open architecture platform; and to demonstrate the integration of OpenLabs modules with existing LISs. PMID- 7889747 TI - ORATEL: telematic system for quality assurance in oral health care (AIM Project A2029). AB - ORATEL is a 3-year project with the ultimate objective of improving oral health through use of appropriate computerized information systems. These tools will promote quality assurance and development in oral health care by using common quality indicators/standards. The project has completed its first phase, during which two European surveys were made, one on quality assurance clinical practices, and another on existing computerized information systems in oral health care. Pan European consensus was reached on 3 and 4 September 1992 when quality assurance indicators for oral health care services were endorsed. A manual on quality assurance indicators in oral health care has also been issued by the project. PMID- 7889748 TI - Telematics in primary health care: a concerted action (AIM-PRIMACARE A2105). AB - The AIM Concerted Action 'Telematics in Primary Care' tries to identify how the applications of telematics to general practice, in the framework of primary health care, can be further developed to improve the quality of health care in Europe. The concerted action started in January 1993 with a broad survey of the 'state of the art' in the different EC-countries. Three working groups will look at the following aspects: communication and data-flows, GP-systems for medical records and contextual aspects of telematics. Preliminary results will be available at the end of 1994. The concerted action hopes to contribute to enhance the importance of primary health care within the AIM-programme. PMID- 7889749 TI - SAMMIE A2032: software applied to multimodal images and education. PMID- 7889750 TI - Concerted action on case mix and resource management. PMID- 7889751 TI - SEISMED: Secure Environment for Information Systems in Medicine. PMID- 7889752 TI - SHINE: Strategic Health Informatics Networks for Europe. AB - The mission of SHINE is to construct an open systems framework for the development of regional community healthcare telematic services that support and add to the strategic business objectives of European healthcare providers and purchasers. This framework will contain a Methodology, that identifies healthcare business processes and develops a supporting IT strategy, and the Open Health Environment. This consists of an architecture and information standards that are 'open' and will be available to any organisation wishing to construct SHINE conform regional healthcare telematic services. Results are: generic models, e.g., regional healthcare business networks, IT strategies; demonstrable, e.g., pilot demonstrators, application and service prototypes; reports, e.g., SHINE Methodology, pilot specifications & evaluations; proposals, e.g., service/interface specifications, standards conformance. PMID- 7889753 TI - TANIT AIM project (A2036): Telematics for ANaesthesia and Intensive Therapy. AB - On-going work relating to the development of advanced telematics systems for Critical Care environments is described. This work is in part sponsored by the Commission of European Communities under the AIM TANIT project. Two example departments have been selected for piloting in the project: Intensive Care and Anaesthesia. The objective of this paper is to outline the complex issues that need to be addressed when developing such systems. PMID- 7889754 TI - Quality assurance in gastroenterology: the Telegastro project. AB - The goal of this Telegastro project is to improve standards of care in gastroenterology by establishing and circulating a 'consensus' view of several aspects of 'good practice' in specific areas of gastroenterology. The background for the study is described, followed by the detailed goals of the project and the modus operandi designed to achieve these goals. Finally, the problems of implementing such a package are discussed along with progress in the first 18 months and schedules for future activities. PMID- 7889756 TI - TELENURSING: European classification of nursing practice with regard to patient problems, nursing interventions and patient outcome, including educational measures. PMID- 7889755 TI - AIM Project A2003: COmputer VIsion in RAdiology (COVIRA). AB - This paper presents an overview of the COVIRA project, AIM Project No. 2003. The COVIRA consortium is performing research in the area of Multimodality Image Analysis, i.e., Registration and Segmentation. Together with results in the areas of Visualization, User Interface, Digital Anatomy Atlas, Conformal 3D Radiation Therapy Planning, and Cerebral Vessel Tree Reconstruction, clinical validation of initial results is under way at six clinical sites in five European countries. The main objective is to achieve an increase in efficiency and quality of healthcare in Neuro-radiological Diagnosis and Treatment Planning. PMID- 7889757 TI - Telematic health--a challenge for medical informatics. PMID- 7889758 TI - The ACOSTA accompanying measure A2106. AB - At a time when the informatics and telecommunications industries are looking for new markets to exploit in relation, for example, to the emerging ISDN and broadband communications networks, there is a need to create a broad consensus in Europe by bringing together systematically the relevant industries including telecom service providers, health care providers, insurance organisations, standardisation experts and policy makers. The aim of the ACOSTA (Consensus Formation and Standardisation Promotion) Accompanying Measure is the creation of more general awareness of the relevant environment among all the parties, better specification of common requirements and options taking better account of the real needs of the users, and enlargement of the common market in health care telematics. PMID- 7889759 TI - A chip card for patients with diabetes. AB - DIABCARD provides the specification for the core of a Chip Card Based Medical Information System (CCMIS) for the treatment of patients with chronic diseases. It will provide an instrument for assessing health care services, improve the links between health care providers and set up communication between the different levels of health care. It will therefore improve the quality of care and thus the life of patients with chronic diseases. DIABCARD concentrates on diabetes at the moment, the concept of the diabetes chip card will, however, be extendable to other chronic diseases. PMID- 7889760 TI - DILEMMA: logic engineering in primary care, shared care and oncology (AIM Project A2005). AB - The aim of DILEMMA is to provide tools for the development of decision support systems for use in general medical practice, hospital-based cancer care, and shared care of cancer and cardiology patients. In primary care, the project intends to provide aids to clinical performance in prescribing, referral and the use of clinical guidelines. The demonstrator applications involve telematics and knowledge-based methodology, using an approach termed logic engineering which combines logic programming and software lifecycle methods. DILEMMA will demonstrate systems to assist shared care and home care which should help reduce pressure on secondary health resources and, by disseminating best practice knowledge, improve patient care and patient quality of life. PMID- 7889761 TI - Education and training in health informatics. AB - In this contribution the AIM Concerted Action Education and Training in Health Informatics (EDUCTRA) is discussed. The activities of the Concerted Action and the results of a survey conducted in 1993 concerning the state-of-the-art of education and training in health informatics in healthcare are presented. PMID- 7889762 TI - EMDIS: European Marrow Donor Information System. AB - EMDIS is an open network between different bone marrow Donor Registries for patients awaiting a transplant and lacking compatible family donors. The network is composed of an identical system in all countries. The architecture makes clear definition between the user system (US) and the EMDIS core system (CS). E-mail approach is used as communication method. A logical model including the EMDIS CS and the US, as well as the list of messages exchanged between US/CS and CS/CS, has been defined. An actually functioning pilot system between three European countries could be used as a trial basis by other research projects. PMID- 7889763 TI - European prototype for integrated care (EPIC). AB - The EPIC project has devised a means by which care workers can share client information between different professions and different locations through the use of a common domain information model for the client dossier, the client reference dossier and the EPIC message. This approach will be tested by its application to the assessment, planning and delivery of care to individual elderly clients in the community with the intention of extending and applying it to other aspects of the business of the community care service and other client groups in the future. PMID- 7889764 TI - ATIM, accompanying measure on the assessment of information technology in medicine. AB - ATIM is an Accompanying Measure under the AIM programme which aims at developing consensus on methods and criteria for assessment of Information Technologies applied in health care and at the application of these methods in two AIM project lines: (a) Knowledge Based and Decision Support Systems and (b) Medical Multimedia Workstations and Images. ATIM builds on, and coordinates assessments and evaluations which are planned in current AIM projects. It consists of workshops, meetings and the coordination of assessments in the two project lines. Networking is an essential element. The main goal of ATIM is to demonstrate the value of assessment to the various actors in this field. One of the end-products of ATIM will be a handbook on how to assess information technologies in medicine, with practical examples from AIM projects. PMID- 7889765 TI - EPISTOL: the future of knowledge based systems and techniques for the health sector. AB - This paper reports on EPISTOL, a project set up to provide a perspective on how knowledge based systems are going to be used in the health sector 5-10 years from now, and how should this expected use influence the planning of research and development work up to that period. The results of the project are aimed to aid the planning of future programmes concerned with research and development in health telematics, namely the fourth Framework Programme of the Commission of the European Communities. PMID- 7889766 TI - An architecture for EEG signal processing and interpretation during sleep (ESPIS). AB - The project's aim is to develop a dedicated workstation in order to process multiple channels of electrophysiological signals in real-time during sleep. In ESPIS we are aiming to define both an architecture and an environment for EEG signal interpretation in medicine based on computer science gold standards (Unix, XWindow, Motif). Signal processing and pattern recognition analysis are provided by parallel processing on a specific developed acquisition architecture (DSP) based on transputers. The main result is a high performance prototype demonstrating signal interpretation during sleep which has already been tested in a medical environment. The overall specifications allow this biomedical device to be extended to other types of medical signals. PMID- 7889767 TI - ESTEEM (European Standardised Telematic Tool to Evaluate EMG Knowledge-Based Systems and Methods): AIM Project A2010. AB - ESTEEM is an AIM project which is primarily concerned with how to develop, integrate and clinically test knowledge-based systems for electromyography (EMG) in order to get them generally acceptable, useful and applicable into disseminated clinical routines. A medical workstation entitled the 'EMG-Platform' on which different kinds of application modules including KBSs can be interfaced to a kernel is being developed. Accordingly, an EMG communication protocol is being developed. The ESTEEM consortium is composed of a technical specialist group and a group of clinical experts in EMG from seven European countries. The last group has, besides extensive data collection for building up a multicentre EMG database, agreed on a common EMG terminology and a subsequent general EMG data set specification which covers the informatic needs for describing an EMG examination of different 'EMG schools'. PMID- 7889768 TI - European Integrated Picture Archiving and Communication Systems, CEC/AIM. AB - A Picture Archiving and Communication System, supported by a multi-media medical distributed image data-base, will be integrated with all other components of a Hospital Information System (HIS). Several services will be set up for intra- and inter-hospital communication. A EurIPACS infrastructure will be implemented, validated and demonstrated. Integration and a user driven approach are the key elements: integrated in a hospital environment stressing the need for having clinical useful systems; integrated with the other information systems; the departmental systems; integrated by means of standards and coordination with CEN TC 251. These key objectives are in stages of pre-prototying. The first systems are being tested in the labs and prepared for the move to the clinical environment. The implementations will result in a second generation distributed PACS architecture test bed, in '95, installed at several clinical sites in Europe. PMID- 7889769 TI - FEST: Framework for European Services in Telemedicine. AB - The main objective of FEST is to develop a framework of common understanding which will assist those wishing to set up a Telemedicine service by providing structured guidance to the information required for such an endeavour. The FEST Framework has been designed and developed as a set of four components, the Question Set, the Advice Component, the Body of Information, and the Descriptive Model. First validation activities (Telecardiology Demonstrator, case and field studies) have fed back experiences to the Framework development. FEST will be the platform for further business planning in European Telemedicine services. PMID- 7889770 TI - The GALEN project. AB - The GALEN project is developing language independent concept representation systems as the foundations for the next generation of multilingual coding systems. It aims to support the flexibility required to cope with the diversity amongst medical applications, while ensuring the coherence necessary for integration and re-use of terminologies. GALEN is developing a fully compositional and generative formal system for modelling concepts: the GALEN Representation and Integration Language (GRAIL) Kernel. Its goal is to overcome many of the problems with traditional coding and classification systems, in particular the combinatorial explosion of terms in enumerative systems and the generation of nonsensical terms in partially compositional systems. It will also provide a clean separation between the concept model and linguistic mechanisms which interpret that model (i.e., the words in a specific language, syntax, alternative phrasings, etc.) in order to allow the development of multilingual systems. GRAIL aims to be formally sound and produce models that are verifiable and contain no contradictions or ambiguities, with realistic human effort. A Coding Reference (CORE) Model of medical terminology covering is being developed which aims to represent the core concepts in for example pathology, anatomy and therapeutics, that have widespread applicability in medical applications. It should also provide the basis for specialist extensions according to the formal principles of GRAIL. The main results of GALEN will be delivered as a Terminology Server (TeS) which encapsulates and coordinates the functionality of the concept module, multilingual module, and code conversion module, and also provides a uniform applications programming interface and network services for use by external applications. PMID- 7889771 TI - GAMES II Project: a general architecture for medical knowledge-based systems. AB - GAMES II aims at developing a comprehensive and commercially viable methodology to avoid problems ordinarily occurring in KBS development. GAMES II methodology proposes to design a KBS starting from an epistemological model of medical reasoning (the Select and Test Model). The design is viewed as a process of adding symbol level information to the epistemological model. The architectural framework provided by GAMES II integrates the use of different formalisms and techniques providing a large set of tools. The user can select the most suitable one for representing a piece of knowledge after a careful analysis of its epistemological characteristics. Special attention is devoted to the tools dealing with knowledge acquisition (both manual and automatic). A panel of practicing physicians are assessing the medical value of such a framework and its related tools by using it in a practical application. PMID- 7889772 TI - The Good European Health Record. PMID- 7889773 TI - BEAM: Biomedical Equipment Assessment and Management. PMID- 7889774 TI - The HELIOS medical software engineering environment. AB - The aim of the HELIOS project is to create an integrated Software Engineering Environment (SEE) to facilitate the development and maintenance of medical applications. HELIOS is made of a set of software components, communicating through a software bus called the HELIOS Unification Bus. The object oriented paradigm is used both as the basic structure for building the software components and as the methodology for modelling, storing and retrieving the entities and procedures used in an application. Development standards include UNIX as operating system and X Window/MOTIF as windowing environment. One of the target applications for the HELIOS prototype is the development of a multimedia medical workstation as a front end to a hospital information system. PMID- 7889775 TI - The intelligent decision mapping patient record (IDMR). AB - IDMR explored in a representative group of diseases, the design of a European patient record, structured on the decisions made by the doctors in caring for patients throughout their hospitalisation in each country of the European Community. Over 350 patients involving 6000 decisions were entered in the database. Working programs in FoxPro and Windows, a demo Apple program and an expert system in Prolog were delivered. The approach worked well. The catalogue of decisions and costs was illuminating. The complexity of a telematics patient record and the clinical work needed to produce it may be underestimated. PMID- 7889776 TI - Computer vision approaches for the three-dimensional reconstruction of coronary arteries: review and prospects. AB - The objective of this article is to define the different stages involved in the 3D reconstruction of arteries and to review, from our experience and from the literature, the solutions already proposed. A full reconstruction framework includes the characterization of the imaging device (in terms of distortion and calibration), the specificity of the image acquisition process, the preprocessing that can be applied, the detection of the vascular structures, the 2D feature formation, the reconstruction itself, and the visualization aspects. They are examined according to a computer vision approach where two or three views are assumed to be available. Their generalization to temporal image sequences are also considered. Some of the material reported here is unpublished. The article allows the reader to identify the true critical issues that are not often clearly mentioned in the literature and the challenges that they convey. A final discussion presents a few perspectives in this area of research. PMID- 7889777 TI - The challenges for hermetic encapsulation of implanted devices--a review. PMID- 7889778 TI - [Point value revision for ambulatory surgery--an intermediate-term evaluation]. PMID- 7889779 TI - [Recommendation on the distribution of EBM 80-83 additional reimbursements between surgeons and anesthetists]. PMID- 7889780 TI - [Intelligent problem solving: what does GmbH practice contribute?]. PMID- 7889781 TI - [In conjunction with the change in the editorship of "Chirur BCD" we present an appreciation of the life and work of Professor Dr. med. Wolfgang Muller-Osten. We begin with a reprint of the laudation presented on the occasion of the 80th birthday in Hamburg 1 August 1990 (J. Bauch)]. PMID- 7889782 TI - [Quality assurance in surgery. New aspects due to the "Decision on a recommended framework for quality assurance in hospital services regarding case statistics and special reimbursement"]. PMID- 7889783 TI - [Sepsis--sepsis syndrome--systemic inflammatory response syndrome]. PMID- 7889784 TI - [Immunosuppression and infection]. AB - The course of prolonged sepsis is characterized by an initial activation of the immune system followed by the transition into a state of immunosuppression. Accordingly, a series of immunosuppressive substances can be detected in the serum of septic patients. On the cellular level many important functions of the unspecific as well as the specific defense systems of the organism are inhibited. As a consequence, immunosuppression may be contributing to the fact, that patients suffering from prolonged sepsis hardly recover with a high risk to end in multiple organ dysfunction. However, increasing efforts to investigate this problem may result in therapeutic approaches which may help to improve the bad prognosis of sepsis. PMID- 7889785 TI - [Oxygen radicals and nitrogen monoxide in sepsis]. AB - Accumulation and stimulation of PMN-leukocytes, enhanced prostaglandin metabolism and tissue hypoxia lead to high concentrations of oxygen radicals and their metabolites in septic shock. Synchroneously, excessive high concentrations of nitric oxide are found, most likely due to the stimulation of its inducible synthetase. Oxygen radicals seem to be attributable for the irreversible tissue damage leading to multiple organ failure in sepsis. High concentrations of nitric oxide induce the typical macro- and microcirculatory derangements normally seen in sepsis. Both mediators are present in the early phase of sepsis and seem to influence the course of disease. Therapeutic interventions such as scavenger therapy or inhibition of the inducible NO-synthetase are promising. The results of the first clinical therapeutic studies, however, were not always conclusive. It is still unclear which scavenger and which inhibitor should be given when and in which dosage in order to improve the outcome of sepsis and septic shock. Furthermore, it remains unclear to which extend oxygen radicals and nitric oxide react with each other, thus possibly potentiating their effects. The open questions still warrant further research and may lead to new therapeutic options improving the morbidity and mortality of this severe disease. PMID- 7889786 TI - [Mediator systems and infection]. AB - Sepsis is the systemic response of the body to an infection. Sepsis-like conditions with nearly identical body reactions, however, are also seen without any evidence of bacteremia. Sepsis is a disease of the host response (specific and non-specific immune system). Depending on the time of the disease process, different mediators (released or newly formed) are involved. This review summarizes the current knowledge and interactions of different cells, cascade systems and mediators in the pathogenesis of sepsis and gives an overview of the approaches and results of current "anti-mediator strategies" to control or modulate inadequate mediator responses. PMID- 7889787 TI - [Surgical therapy of rectal prolapse using rectopexy and resection. Effect of resection treatment on postoperative constipation and sphincter muscle function- a follow-up study of 112 patients]. AB - Between 1985 and 1991, 112 patients underwent posterior abdominal rectopexy (n = 59 Ivalon sponge, n = 53 Vicryl-rectopexy) for complete rectal prolapse. The follow-up period was 3 months to 9 1/2 years. 25 patients with severe constipation and rectal prolapse were treated by rectopexy combined with colectomy (left colectomy n = 18, sigmoidectomy n = 3, ileo-sigmoidostomy n = 4). Left colectomy combined with Ivalon or Vicryl-rectopexy does not seem to increase operative and postoperative morbidity but tends to diminish constipation in 84% of patients. There were no complications attributable to bowel resection or anastomosis. Following abdominal rectopexy without resection constipation was reduced 7.5% only, the bowel function was unchanged in 69% and obstipation was improved after the operation in 23%. In the group of patients without evident constipation (n = 74) treated with synchrone resection has no benefit with regard to the new occurred constipation, recurrence prolapse and continence ability. Infection around the prosthesis developed in 1.5% in the resection group, and in 2.1% in the rectopexy alone group. The prolapse recurrence rate was 2.6%. Conclusion. Resection in conjunction with abdominal rectopexy tends to diminish postoperative constipation does not seem to increase operative morbidity, and is indicated in patients with constipation only. PMID- 7889788 TI - [Endorectal ultrasound for evaluating perirectal processes]. AB - Between July 1992 and December 1993 we examined 258 patients by endorectal ultrasound at the Surgical Department of the University of Wurzburg. In 24 (9.3%) patients we found 27 perirectal lesions. These comprised abscesses, cysts, primary and secondary malignancies, as well as various benign tumours. All lesions but one underwent histological and/or microbiological examination. Endosonographic assessment with regard to size, location and anatomical structure was correct in 24 (89%) cases. We performed ultrasound-guided, transrectal aspiration in six patients. Endorectal ultrasound is a useful complementary imaging device in the assessment of pararectal disease. Owing to its high resolution it may be superior to other methods (e.g. CT or MRI). Another advantage is the possibility of ultrasound-guided aspiration biopsy. Precise knowledge of the topographic anatomy and its endosonographic appearance is of great importance. PMID- 7889789 TI - [Resection of solitary liver metastases of malignant melanoma]. AB - Patients with solitary metastasis of melanoma may benefit from resection, although diffuse organ involvement is common. Recent results in immunotherapy of metastatic melanoma are impaired by early local recurrence, leading to consolidation surgery. Two patients with solitary liver metastasis were treated by liver resection. In one patient in January 1993, atypical resection was performed after partial remission induced by regional adoptive immunotherapy with LAK-cells and Interleukin-2. In September 1983 right hemihepatectomy was done in one patient for large metastasis without preceding therapy. Until now there is no evidence of disease in both patients. The metastasis were 14 cm without and 3.5 cm after (5.3 cm before) immunotherapy in diameter. On histologic examination we found only a slight necrosis without marked immunological reaction like mononuclear cell infiltration or fibrotic demarcation in the specimen of the patient without forgoing therapy. In the specimen of the patient after immunotherapy, the metastasis was necrotic. It was encapsulated by fibrous tissue which was infiltrated by lymphoid cells. The microscopic evaluation revealed some clots of vital tumorcells. The resection of solitary liver metastasis of melanoma with or without immunotherapy is recommended. The rational for consolidation surgery for melanoma metastases after successful immunotherapy is based on the histologically proven vital tumor cells in necrotic metastasis, which are responsible for early local recurrence. PMID- 7889790 TI - [Diagnostic and therapeutic strategy in multiple insulinoma]. AB - Four of 59 patients with organic hyperinsulinism had multiple insulinomas and two patients a micro- and macroadenomatosis. Excluding patients with adenomatosis 3 of 10 tumors could be detected preoperatively by ultrasound (5 of 10 by CT). 6 of 7 macroadenomas could be visualized by angiography. Intraoperatively 9 of 10 macroadenomas were palpable. The nonpalpable tumor could be localized by intraoperative ultrasound. Pancreatic resection had better results than multiple enucleations. Excisional biopsy is recommended to exclude nesidioblastosis or microadenomatosis. PMID- 7889791 TI - [Continuous single layer anastomosis as the standard procedure in the gastrointestinal tract]. AB - The continuous suture by single layer technique is suitable for all anastomoses in the gastrointestinal tract. Anastomotic dehiscence rate has been examined and amounts 1.7% for anastomoses in the stomach 0.3% in the small intestine and 2.8% in the colon. In comparison with other techniques the anastomosis is safe and easy to learn. Costs and time of surgery can be reduced significantly. PMID- 7889792 TI - [Pancreas resection with the surgical stapler. Technique and results]. AB - In a consecutive series of 42 pancreatoduodenectomies and 17 distal pancreatectomies we evaluated the applicability of the stapler TA-55 for transecting the pancreas parenchyma. In 90% of Whipple's operations and in 88% of distal pancreatectomies the transection of the pancreas was successfully accomplished by using the TA-55. The two rows of steel staples lead to a uniform closure of the pancreatic tissue and thus provided an excellent precondition for pancreatic stump healing and creation of a pancreaticojejunal anastomosis. Pancreatic fistulas occurred in 3 cases (5%) and were all successfully treated conservatively. Summarizing our experience, the stapler TA-55 can be recommended particularly for the transection of normal and fragile pancreatic tissue. PMID- 7889793 TI - [Esophagus carcinoid--a rare differential diagnosis in malignant esophageal neoplasia]. AB - Two of patients with a carcinoid tumor of the esophagus are reported, an extremely rare localisation. Eight months after esophagectomy the 50-year-old male is entirely well and without any sign of recurrence; the 56-year-old female has died in this time. Our two cases are discussed in comparison with seven cases found in the literature. PMID- 7889794 TI - [Incidental endoscopic finding--ileum carcinoid. Treatment strategy and prognostic factors]. AB - The malignancy of gastro-intestinal carcinoids is dependent on localisation and size of the tumor. Tumors of the small bowel seem to have a tissue infiltration depth and extension independent of the primary tumor size. We give a case report of a patient with a carcinoid tumor in the terminal ileum with a diameter of 5 mm and a tissue infiltration depth to submucosa. Based on the immunohistochemical investigation of lymphnode metastases for little, accidentally found carcinoids in the ileum a hemicolectomy with wide mesenteric lymph resection is necessary. PMID- 7889795 TI - [Gas gangrene after cholecystectomy]. AB - We report on a case of an infection by clostridium perfringens (gas gangrene) following cholecystectomy and ERCP. Reviewing the literature, mode and risk of infection and principles of therapy are discussed. PMID- 7889797 TI - [References for planning and implementation of clinical studies in the areas of somatic cell and gene therapy. German Society of Gene Therapy]. PMID- 7889796 TI - [Transplantation of the kidney of an 80-year-old donor after complex revascularization with good transplant function]. AB - There is no age limit in kidney donation. Kidney function has to be evaluated on an individual basis even in elderly donors. We report the transplantation of the kidney of an 80-year-old donor with good organ function postoperatively. Complex revascularization had to be performed because of arteriosclerosis in two of three renal arteries. PMID- 7889798 TI - Quality of life in younger persons with an implantable cardioverter defibrillator. AB - Although a life-saving device for people with potentially lethal ventricular arrhythmias, the implantable cardioverter defibrillator (ICD) also imposes numerous limitations. This is especially true for active younger people who will have many more years of trying to cope with the limitations the device imposes. The authors report how younger people with ICDs describe the quality of their life, and suggest ways nurses can help these individuals manage with an ICD. PMID- 7889799 TI - An algorithm to distinguish the need for sedative, anxiolytic, and analgesic agents. AB - This article discusses the use of an algorithm developed by nurses at the University of Minnesota Hospital and Clinic in Minneapolis, that can be used to distinguish the need for sedative, anxiolytic, and analgesic agents for patients in the medical intensive care unit (MICU). Many problems associated with patient sedation and analgesia exist within the critical care environment. These problems include undersedating patients with neuromuscular blockade; rapidly tapering or abruptly discontinuing high-dosage sedation, which often results in withdrawal symptoms; over-use of high-dosage continuous intravenous infusions of short acting benzodiazepines and analgesics; failure to recognize delirium; and resistance to modifying drug regimens when patient outcomes are not satisfactory. PMID- 7889800 TI - Applying a sedation algorithm to ICU patients in pain. PMID- 7889801 TI - Capnography: assessing end-tidal CO2 levels. AB - The purpose of this article is to describe the nurse's role in caring for patients with capnography. Capnography provides a continuous and non-invasive measure of arterial partial pressure of carbon dioxide (PaCO2) throughout the entire respiratory cycle. Used correctly, this technology assists the critical care nurse in providing adequate oxygenation and ventilation to the unstable patient. PMID- 7889802 TI - A relaxation protocol to reduce patient anxiety. AB - Relaxation and music therapy have shown promise as anxiety-reducing interventions for patients in critical care settings. The challenge for nurses is to incorporate these modalities of care into effective clinical strategies. This article describes one method of introducing relaxation therapy to the anxious patient within the context of the Dungan Model of Dynamic Integration. PMID- 7889803 TI - Preventing complications in infant botulism. AB - By recognizing early signs of complications and intervening appropriately, the nurse plays a critical role in improving outcomes for infant botulism patients. The profound impact of the disease upon the family unit may be lessened by meticulous nursing care, parental support and education. PMID- 7889804 TI - Pain medication for the patient following treatment withdrawal. AB - What is nursing's responsibility for pain control following the decision to withdraw life support? Should nurses be free to administer whatever amount of sedation they feel is necessary to provide adequate pain control for their patient? What should the nurse do if the physician prescribes a subtherapeutic dose of pain medication? The following article presents a case and analyses the nurse's moral duty to do no harm in this type of situation. PMID- 7889805 TI - Occupational asthma and related respiratory disorders. AB - Occupational rhinitis is a common but generally underreported entity. Although it may occur alone, it is frequently associated with occupational asthma. Occupational asthma may have one of several presentations that are difficult to distinguish from non-work conditions. The respiratory tract acts as the final common pathway for all inhaled environmental pollutants, whether encountered in the home or at work. More than 200 chemicals have been incriminated as a cause of work-related asthma. It is said that about 2% of the 10 million Americans who have asthma acquired it as a result of some chemical irritant or immunogen in their work environment. A number of predisposing factors facilitate the development of work-related asthma. These include industrial conditions, climatic factors, atopic predisposition, smoking, recreational drug use, viral infection, nonspecific bronchial hyperreactivity, and a variety of miscellaneous factors. Pathogenetically, occupational asthma may be immunologic or nonimmunologic in nature. The immunologic variants involve sensitization to a variety of large molecular-weight constituents. The major nonimmune variant is referred to as inflammatory bronchoconstriction or reactive airways dysfunction syndrome (RADS). There are well-defined criteria for the diagnosis of immunologic and nonimmunologic asthma. The several clinical variations of occupational asthma can be difficult to distinguish from nonindustrial disorders. The most common presentation in practice involves the worker with preexistent asthma who has been adversely affected by work exposures. Occasionally these industrial exposures precipitate permanent impairment. It is clear, however, that occupational asthma is not a single, simple, or homogeneous entity, even when a single specific causal factor can be identified in the workplace. Therefore the physician must be aware of the patient's entire medical history and the precise occupational exposures and must have convincing physiologic evidence that demonstrates a cause and-effect relationship before making a definitive diagnosis of work-related asthma. Once the diagnosis is established, the worker should be removed from the work-place. If the diagnosis is made in a timely fashion, the patient should experience a significant improvement. The major factor in determining a poor prognosis in occupational asthma is the duration of exposure before the diagnosis is established. Prevention of the disorder is the best therapeutic intervention. PMID- 7889806 TI - Behavioral and developmental effects of two 3,4-methylenedioxymethamphetamine (MDMA) derivatives. AB - The effects of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstacy') and two structurally related compounds, N-methyl-1-(3,4-methylenedioxyphenyl)-1 ethanamine (MDM1EA) and N-methyl-1-(3,4-methylenedioxyphenyl)-3-butanamine (HMDMA) were examined in two preparations: (i) a drug discrimination procedure in MDMA-trained rats and (ii) the chicken embryo, for determination of the direct effects of these compounds on the developing organism. The highest doses of MDM1EA and HMDMA partially substituted for MDMA, whereas higher (30-60 mg/kg) doses of HMDMA evoked clonic seizures in a separate group of rats. In chicken embryos MDMA had no effect on body, brain or liver weight, while the highest dose of MDM1EA decreased body weight and the 2 lowest doses of HMDMA increased body weight. All doses of HMDMA decreased liver weight (expressed as % body weight) when compared with contemporaneous water-treated controls. Taken together, the results of these experiments suggest that structurally related compounds share some stimulus properties with MDMA and may therefore share abuse liability. Furthermore, both MDMA-related compounds produced adverse effects on the developing organism, whereas MDMA did not. PMID- 7889807 TI - Alcohol use among primary care patients: comparing an HMO with county clinics and the general population. AB - A probability sample of all patients seen in the four health maintenance organization (HMO) primary care clinics in one Northern California county (N = 314) are compared to patients from all five of the county-operated primary care clinics in the same county (N = 394) and to the general population of the county (N = 3069) on demographic characteristics, drinking patterns and alcohol-related problems. The HMO clinic patients were less likely to report frequent, heavy drinking, drunkenness or alcohol-related problems during the last year compared to those in the county clinics sample, and they were also less likely to report heavy and problem drinking compared to those in the general population. These data suggest problem drinking may not be over-represented in primary care practice in general, but rather may be more closely associated with characteristics of clientele served by a primary care practice than with those characteristics associated with a need for medical attention. PMID- 7889808 TI - Effect of pre-treatment with aspirin on alcohol-induced neural tube defects in the TO mouse fetuses. AB - This study was planned to investigate the effects of ethanol on the genetic susceptibility of the TO mouse to neural tube malformations and to determine the ameliorative effects, if any, of aspirin a potent prostaglandin inhibitor. The TO mouse exhibits a spontaneous incidence of 3.6% exencephaly. The mice were exposed to single (i.p.) dose of 0.03 ml/gm body weight of a solution of (25%v/v) of absolute alcohol in physiological saline on day 7 or 8 of gestation. Subteratogenic doses (150 or 200 mg/kg) of aspirin were administered (i.p.) an hour before ethanol exposure. Fetuses were collected on day 18 and compared with those of the untreated, and saline treated pair-fed pair-watered controls as well as with those of the aspirin alone treatment group. A total of 175 litters were studied. Alcohol caused a three-fold increase against the background incidence of exencephaly. Several craniofacial anomalies and growth retardation were also observed. Alizarin red-S stained skeletal preparations revealed extensive malformations of the craniofacial skeleton in the exencephalic fetuses. Both doses of aspirin administered prior to alcohol treatment significantly accentuated the alcohol-induced prenatal mortality. The rescue effect of aspirin on alcohol-induced intrauterine growth retardation was also significant although fetal weight was not restored to levels comparable to those of the controls. Pre treatment with aspirin (both 150 and 200 mg/kg) on day 8 of gestation resulted in a numerical, though not statistically significant increase in alcohol-induced exencephaly. On the other hand pre-administration of the lower dose on day 7 exencephaly. On the other hand pre-administration of the lower dose on day 7 of gestation caused a significant reduction while the higher dose gave rise to a significant increase in the incidence of this malformation. Aspirin also reduced the frequency of alcohol-induced arched palate and the baseline exencephaly. These data provide evidence for the possible interaction of alcohol with the genetic susceptibility to exencephaly in this strain of mice. The lack of a clear dose-dependent antagonistic effect of aspirin on alcohol-induced exencephaly suggests that the production of this malformation is probably not mediated by prostaglandin as it was shown for limb and renal abnormalities (Randall, C.L., Anton, R.F. and Becker, H.C. (1991). Aspirin dose dependently reduces alcohol induced birth defects and prostaglandin E levels in mice. Teratology 44, 521 529). PMID- 7889809 TI - Evaluation of the abuse liability of aminorex. AB - Aminorex is a cyclic phenylisopropylamine that has been marketed as an anorectic. Despite obvious pharmacological similarities to the amphetamines, little is known about its liability for abuse. In the present study, one group of rhesus monkeys (n = 3) was prepared with intravenous catheters and allowed to self-administer either methohexital or saline in daily experimental sessions. When methohexital and saline self-administration were stable and clearly different, various doses of aminorex (0.001-0.1 mg/kg/injection) were made available for self administration. Aminorex maintained self-administration above that maintained by saline and slightly lower than that maintained by methohexital in all monkeys. The discriminative stimulus effects of aminorex were evaluated in rhesus monkeys trained to discriminate d-amphetamine (n = 3) or pentobarbital (n = 4) from saline. Aminorex substituted completely for d-amphetamine as a discriminative stimulus but engendered little or no pentobarbital-appropriate responding. Aminorex stimulated locomotor activity in mice and exacerbated the withdrawal syndrome in rats that were dependent upon pentobarbital. These findings indicate that aminorex is a psychomotor stimulant that would be predicted to have significant d-amphetamine-like abuse liability in humans. PMID- 7889810 TI - Diagnostic concordance of substance use disorders in DSM-III, DSM-IV and ICD-10. AB - Diagnostic concordance of DSM-III, DSM-IV and ICD-10 was tested in a heterogeneous unrestricted sample of 370 clinical cases drawn from a regional consortium. Agreement for abuse/harmful use, dependence, and the collapsed category of 'any diagnosis' was studied across eight drug classes. A probabilistic approach to the cross-classifications based on configural frequency analysis was applied, permitting the computation of four indices of agreement. In contrast to earlier studies, ICD-10 appeared to be the most inclusive system, and often diagnosed cases that were undiagnosed by both DSMs. Generally satisfactory coherence between the ICD-10 harmful use category and the DSM category of abuse was found, but this agreement was often due to a preponderance of negative or undiagnosed cases; disagreement was common on which cases in particular warrant a mild diagnosis. In general, the greatest diagnostic concordance was observed for sedative/hypnotics, opiates and alcohol, the poorest for amphetamines, cocaine and PCP. The analytic approach produced an array of cross-system relationships that are more complex and conditional than those previously reported, and scientists and clinicians are cautioned to study particular drugs, diagnostic levels and measures of concordance before applying cross-system results to their own data or design needs. PMID- 7889811 TI - Temperament: a salient correlate of risk factors for alcohol and drug abuse. AB - A sample of sons of substance abusing (SA+; n = 39) and normal fathers (SA-; n = 45) were studied to determine the relative contribution of temperament characteristics and paternal lifetime history of substance abuse as factors that are putatively linked to risk for substance abuse. Cluster analyses of sons' and fathers' scores on the Revised Dimensions of Temperament Survey (DOTS-R) yielded 'difficult' temperament and normative temperament clusters. In a comparison of risk liability associated with SA+/SA- status versus temperament cluster membership, boys in the difficult temperament cluster were differentiated from boys in the normative temperament cluster on cognitive, behavior, family and peer affiliation risk factors. In subsequent logistic regression analyses, 85% of sons in the difficult temperament cluster and 72% of sons in the normative temperament cluster were correctly classified by their risk factor scores. PMID- 7889812 TI - Relationship of specialty and access to substance use among registered nurses: an exploratory analysis. AB - Substance use patterns among nurses and women in general are understudied, especially how substance use relates to the work environment. Using an anonymous survey mailed to a population based random sample of registered nurses, this study presents the first empirical evidence that working in a critical care specialty combined with easy workplace access to drugs is associated with a high likelihood of illicit drug use among nurses (O.R. = 6.2). PMID- 7889813 TI - Contingent methadone take-home doses reinforce adjunct therapy attendance of methadone maintenance patients. AB - Two studies utilized within-subjects designs to determine whether take-home methadone doses can reinforce adjunct therapy attendance of drug abuse patients. These studies varied the reinforcement density and the schedule of methadone take home doses. In Study 1, patients (n = 10) either could or could not receive a take-home following each therapy session. Study 2 patients (n = 15) could either earn take-homes following each therapy session attended (i.e., 2 take-homes per week) or could earn one take-home dose following each attendance to two consecutive sessions attended. In both studies experimental conditions alternated during three-week blocks of time. Across studies, any reinforcement by take-home doses produced more attendance at therapy sessions than that observed in the no reinforcement condition. Take-home incentive effects were strongest when each of the two weekly therapy sessions was reinforced by a methadone take-home dose. Increased attendance was not associated with reduced drug use, due perhaps to high rates of pre-study drug use and limited therapy duration. Contemporary opioid abusers present with multiple problems that methadone was never intended to treat. The present studies illustrate a method by which methadone treatment can improve the likelihood of delivering other services that may prove effective in treating some of these problems. PMID- 7889815 TI - [Arteriosclerosis of the thoracic aorta as a source of systemic emboli. A clinico pathologic study]. AB - The significance of the thoracic aorta as a source of systemic emboli in addition to other sources of embolism remains unexplained. A study of 120 consecutive necropsies (65 men, 55 women; mean age 71 [29-94] years) analysed the possible correlation of the severity of arteriosclerosis of the aorta, the carotid arteries and the arteries at the base of the brain as well as cardiac changes, with potential sources of emboli and with proven emboli (n = 39). Complex and fibrous plaques in the arch of the aorta, ipsilateral carotid artery stenoses, a history of atrial fibrillation and heart weight correlated significantly with emboli on both uni- and multivariant analysis. But the presence of calcified and complex plaques in the descending aorta, as well as moderate and severe arteriosclerosis in the arteries at the base of the brain, correlated significantly only on univariant analysis. Ischaemic brain lesions had been clinically silent in twelve of 32 cases, while visceral emboli had been silent in nine out of ten cases. -It is concluded from these data that, in addition to the cardiac chambers and arteriosclerosis of the arteries at the base of the brain, advanced arteriosclerosis of the aortic arch is an important source of systemic emboli. As many of the emboli remain silent, their incidence is probably underestimated clinically. PMID- 7889814 TI - Effects of marijuana history on the subjective, psychomotor, and reinforcing effects of nitrous oxide in humans. AB - An experiment using marijuana users and non-users was conducted to assess whether the reinforcing, subjective, or psychomotor effects of nitrous oxide were influenced by a subject's drug history. Subjects in the first four sessions sampled 40% nitrous oxide in oxygen and 100% oxygen (placebo), and then over the next three sessions, chose which agent they wished to inhale. Choice distributions between the two groups did not differ significantly, and nitrous oxide choice rates were less than 50% in both groups. However, a history of marijuana use appeared to intensify some of the subjective effects induced by nitrous oxide inhalation. PMID- 7889816 TI - [Short-term triple therapy with pantoprazole, clarithromycin and metronidazole for the healing of Helicobacter pylori infection]. AB - In a prospective study 27 patients (13 women, 14 men; mean age 62 [45-83] years) with Helicobacter (H.) pylori associated disease received over 7 days pantoprazole (40 mg twice daily), clarithromycin (500 mg twice daily) and metronidazole (500 mg twice daily). Six patients had gastric ulcer, 4 duodenal ulcer, 4 erosive gastritis, 6 erosive duodenitis and 7 had H. pylori-positive functional dyspepsia. Pre-treatment oesophago-gastro-duodenoscopy was combined in 4 patients with antral and in 4 others with body-of-stomach biopsies to demonstrate H, pylori (urease test, specific culture and histology). The H. pylori status was checked with the 13C-urea breath test 4 weeks after the end of treatment. In addition, 9 patients with peptic ulcer were examined endoscopically at least 2 weeks after onset of the treatment to check for any healing of the ulcers, 25 of the patients completed the study according to the protocol. The H. pylori eradication rate was 100% (25 of 25 patients), while the "intention to treat" analysis gave a rate of 92.6% (25 of the 27 patients). The peptic ulcers were found to be healed in all 9 patients who had been endoscoped. One woman developed a reversible stomatitis, but the drug treatment did not have to be stopped. -These findings indicate that short-term triple treatment in the described manner is efficacious in curing H. pylori infection and any peptic ulcer. It is thus a highly promising treatment of H. pylori-associated diseases. PMID- 7889818 TI - [The hereditary form of pincer nail syndrome]. AB - Over a period of six months a 41-year-old woman had recurrent acute paronychia of both large toes. On inspection all toes had pincer nails. She had no metabolic abnormalities and no history of trauma. Onychomykosis was excluded. Under conduction anaesthesia an Emmert plasty (Haneke's modification) was performed: it revealed osteocartilaginous exostoses in the area of nail gryposis. Subsequent radiological examination showed distally directed exostoses on the tibial side of all toe phalanges, which is an obligatory criterion for the hereditary form of the pincer nail syndrome. PMID- 7889817 TI - [Autoimmune hepatitis, autoimmune gastritis, hypergastrinemia and stomach carcinoid]. AB - A 48-year-old woman with type II diabetes developed fatigue, arthralgia and myalgia. A few weeks later she was found to have hepatomegaly. The erythrocyte sedimentation rate was raised (53/93 mm), as were liver enzyme activities (GOT 186 U/l; GPT 240 U/l; gamma-GT 199 U/l), the gamma-globulin levels (40.7%;IgG 4470 mg/dl, IgA 698 mg/dl, IgM 245 mg/dl), antinuclear antibodies and antibodies against double-strand DNA, smooth muscles and actin. Laparoscopy revealed small nodular liver cirrhosis. The autoimmune hepatitis was treated with prednisolone (initially 60 mg daily, then reduced to 10 mg daily) and azathioprine (initially 100 mg daily, reduced to 50 mg daily). The symptoms markedly improved. But one year later, during follow-up examination, gastric polyps were found, excised and histologically found to be carcinoid. The gastrin level was raised to 765 pg/ml. Another year later the liver cirrhosis had advanced further and the type A gastritis was still present, but there was no sign of carcinoid recurrence. PMID- 7889819 TI - [The neuralgic shoulder myatrophy. The differential diagnosis of shoulder-arm syndromes]. PMID- 7889821 TI - [Ammonia determination in hepatic encephalopathy]. PMID- 7889820 TI - [Reperfusion therapy in acute myocardial infarct]. PMID- 7889822 TI - [Glucose substitutes in parenteral nutrition]. PMID- 7889823 TI - [Guarana]. PMID- 7889824 TI - [Postpoliomyelitis syndrome]. PMID- 7889825 TI - [Angina pectoris and normal coronary angiogram in arterial hypertension]. PMID- 7889827 TI - [Delayed fatalities and survival after neoplastic diseases in children. Consequences for curative therapy plans]. PMID- 7889826 TI - [Elevated gamma-glutamyltransferase]. PMID- 7889828 TI - [Effects of HLA mismatches on the function rate of cadaver kidneys after the first transplantation]. PMID- 7889829 TI - Modulations of hepatic gamma-glutamyltranspeptidase and N-hydroxy-N-2 fluorenylacetamide sulfotransferase activities following treatment of rats with a hepatocarcinogenic regimen: effect of partial hepatectomy. AB - The feasibility of using biochemical assays of gamma-glutamyltranspeptidase (gamma-GTP) and N-hydroxy-N-2-fluorenylacetamide sulfotransferase (N-OH-2-FAA ST) activities to monitor the effects of treatment of male Sprague-Dawley rats with a two-stage hepatocarcinogenic regimen was investigated. One week after initiation with diethylnitrosamine (200 mg/kg of bw), the rats were treated with 10 oral doses within 2 weeks of N-2-fluorenylacetamide (2-FAA) at 0.05 mmole/kg or vehicle (corn oil) at 5 ml/kg of body weight. After five doses of 2-FAA or corn oil, half of the rats in each group underwent partial (70%) hepatectomy (PH). Three days after completion of 2-FAA treatment, gamma-GTP activity increased approximately 8-fold in the livers of both the nonhepatectomized (-PH) and hepatectomized (+PH) groups. After 17 days, the enzyme activity decreased to the control level in the -PH group but increased 3.1-fold above the control level in the +PH group. After 31, 66, and 87 days, gamma-GTP activity increased only 1.4- to 2.6-fold in the -PH group, whereas that of +PH group increased 15- to 32-fold. N-OH-2-FAA ST activity, determined 3 days after completion of 2-FAA treatment, decreased by approximately 60% in the -PH and +PH groups. After 17 days, the effect of PH became evident in that the losses of N-OH-2-FAA ST activity were smaller (20%) in the -PH than in the +PH group (45.5%). After 31, 66, and 87 days, the respective decreases of 27, 29, and 41% in the +PH group were significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889830 TI - Metabolism of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) in isolated liver cells from guinea pig, hamster, mouse, and rat. AB - The metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant compound of the aminoimidazoazaarens (AIA) group of mutagens/carcinogens isolated from the crust of fried and broiled meat, was examined in freshly isolated hepatocytes from untreated rat, mouse, hamster, and guinea pig. Activation was evaluated by the total level of covalent binding of PhIP to macromolecules. Rat hepatocytes had the lowest rate of metabolism, both to reactive and detoxified metabolites. The products were identified as 4'-PhIP sulfate, PhIP-glucuronide, and N(OH)-PhIP-glucuronide. The ring hydroxylation rate was much greater in mouse hepatocytes, the main products being 4'-PhIP sulfate and 4-hydroxy-PhIP. The level of covalent binding in the mouse hepatocytes exceeded those of the rat and guinea pig at high doses of PhIP. An extensive metabolism was seen in guinea pig hepatocytes, the major products being 4'-PhIP-sulfate, 4'-O-PhIP glucuronide, PhIP-glucuronide, and N(OH)-PhIP glucuronide. In addition, several other unknown metabolites were formed. However, the amount of covalent binding in guinea pig hepatocytes was similar to that in rat hepatocytes. Covalent binding of PhIP metabolites was highest in hamster hepatocytes. Three of the main metabolites were identified as 4'-PhIP-sulfate, 4' O-PhIP-glucuronide, and PhIP-glucuronide, but several unknown PhIP metabolites also were formed. Only minor amounts of N(OH)-PhIP-glucuronide were produced in the hamster. The present study shows that both the direct detoxification of PhIP and further conjugation of the 2-hydroxylamino-PhIP to reactive and/or detoxified metabolites are important for the resulting covalent binding. PMID- 7889831 TI - Analysis of 4-aminobiphenyl-DNA adducts in human urinary bladder and lung by alkaline hydrolysis and negative ion gas chromatography-mass spectrometry. AB - Analysis of carcinogen-DNA adducts has been regarded as a useful means of assessing human exposure to chemical carcinogens. We have established a method for quantitation of 4-aminobiphenyl (4-ABP)-DNA adducts by alkaline hydrolysis and gas chromatography with negative ion chemical ionization mass spectrometry (GC-NICI-MS). Aliquots of DNA (typically 100 micrograms/ml) were spiked with an internal standard, d9-4-ABP, and were hydrolyzed in 0.05 N NaOH at 130 degrees C overnight. The liberated 4-ABP was extracted with hexane and derivatized using pentafluoropropionic anhydride in trimethylamine for 30 min at room temperature prior to GC-NICI-MS. With in vitro [3H]N-hydroxy-4-ABP modified DNA standards, we observed 59 +/- 7% (n = 9) recovery of the 4-ABP and a linear correlation between hydrolyzed 4-ABP and the adduct levels ranging from about 1 in 10(8) to 1 in 10(4) nucleotides (r = 0.999, n = 9). The method was further validated by comparison of the results with that obtained by the 32P-postlabeling method. There was excellent agreement (r = 0.994, p < 0.001) between the two methods for quantitation of the adduct in eight samples of Salmonella typhimurium DNA treated with 4-ABP and rat liver S9, although the 32P-postlabeling method gave slightly higher values. The DNA adducts in 11 human lung and 8 urinary bladder mucosa specimens were then determined by our GC-NICI-MS method. The adduct levels were found to be < 0.32 to 49.5 adducts per 10(8) nucleotides in the lungs and < 0.32 to 3.94 adducts per 10(8) nucleotides in the bladder samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889832 TI - Oxidative conversion of isothiocyanates to isocyanates by rat liver. AB - This report describes the oxidative metabolism of isothiocyanates to isocyanates catalyzed by rat liver microsomes. Incubation of 2-naphthylisothiocyanate, microsomes, and NADPH yielded either N,N'-di-naphthylurea or, on inclusion of 2 aminofluorene in the incubations, N-2-naphthyl-N'-2-fluorenylurea. These ureas were formed by the production of the known genotoxicant, 2-naphthylisocyanate, which reacted with its hydrolysis product, 2-aminonaphthalene, to yield the symmetrical urea, or with 2-aminofluorene to form the mixed urea. Formation of N,N'-di-2-naphthylthiourea was also observed because 2-aminonaphthalene reacted with the substrate. Urea formation was dependent on the microsomes, NADPH, and oxygen. Use of microsomes from rats previously treated with Aroclor 1254 increased urea formation greater than 10-fold. The enzyme activity was inhibited by alpha-napthoflavone, flavone, or CO, and slightly inhibited by metyrapone, 7 ethoxycoumarin, or SKF-525A. It was not inhibited by methimazole or paraoxon, suggesting that neither flavin-containing monooxygenase nor hydrolytic enzyme was involved. These data are consistent with a cytochrome P450-dependent, oxidative desulfuration of 2-naphthylisothiocyanate to yield 2-naphthylisocyanate. Further studies with the isomeric 1-naphthylisothiocyanate and the dietary benzylisothiocyanate showed that they can also be metabolized to their isocyanates, as evidenced by the trapping of isocyanates with 2-aminofluorene to form the mixed ureas. PMID- 7889833 TI - Evidence for direct-acting oxidative genotoxicity by reduction products of azo dyes. AB - The intestinal flora forms a complex ecosystem that metabolizes dietary and endogenous nutrients under primarily anaerobic conditions. The ingestion of azo dyes has been proposed as one source of potential genotoxic agents. Many intestinal bacteria are able to reduce the azo bond (termed azofission), which liberates the substituted naphthol compounds. The standard Ames test has not demonstrated mutagenicity either by various common food colorings or by their reduced end products in Salmonella typhimurium strains TA98 and TA100. In contrast, genetic toxicity was demonstrated in the Escherichia coli differential kill assay and in S. typhimurium TA102 for the reduced dyes. The superoxide free radical was produced by the azo dyes only after reduction by the intestinal bacteria Enterococcus faecalis and Bacteroides thetaiotaomicron. PMID- 7889834 TI - Reactions of oxidatively activated arylamines with thiols: reaction mechanisms and biologic implications. An overview. AB - Aromatic amines belong to a group of compounds that exert their toxic effects usually after oxidative biotransformation, primarily in the liver. In addition, aromatic amines also undergo extrahepatic activation to yield free arylaminyl radicals. The reactive intermediates are potential promutagens and procarcinogens, and responsible for target tissue toxicity. Since thiols react with these intermediates at high rates, it is of interest to know the underlying reaction mechanisms and the toxicologic implications. Phenoxyl radicals from aminophenols and aminyl radicals from phenylenediamines quickly disproportionate to quinone imines and quinone diimines. Depending on the structure, Michael addition or reduction reactions with thiols may prevail. Products of sequential oxidation/addition reactions (e.g., S-conjugates of aminophenols) are occasionally more toxic than the parent compounds because of their higher autoxidizability and their accumulation in the kidney. Even after covalent binding of quinone imines to protein SH groups, the resulting thioethers are able to autoxidize. The quinoid thioethers can then cross-link the protein by addition to neighboring nucleophiles. The reactions of nitrosoarenes with thiols yield a so-called "semimercaptal" from which various branching reactions detach, depending on substituents. Compounds with strong pi-donors, like 4 nitrosophenetol, give a resonance-stabilized N-(thiol-S-yl)-arylamine cation that may lead to bicyclic products, thioethers, and DNA adducts. Examples of toxicologic implications of the interactions of nitroso compounds with thiols are given for nitrosoimidazoles, heterocyclic nitroso compounds from protein pyrolysates, and nitrosoarenes. These data indicate that interactions of activated arylamines with thiols may not be regarded exclusively as detoxication reactions. PMID- 7889835 TI - Structural requirements for the ferrihemoglobin-forming activity of glutathione S conjugates of 4-dimethylaminophenol. AB - 4-Dimethylaminophenol (DMAP) is a suitable cyanide antidote that rapidly forms ferrihemoglobin by catalytic transfer of electrons from ferrohemoglobin to oxygen. Deleterious methemoglobinemia, because of the catalytic cycling, is prevented by side reactions of oxidized DMAP with thiols, particularly with glutathione (GSH). In human red cells, both in vitro and in vivo, the formation of a transient bis-glutathione and a stable tris-glutathione adduct was observed. To investigate the reactivity of GSH adducts of DMAP, we synthesized various thioethers by oxidizing DMAP with PbO2 in 0.1 M sulfuric acid followed by reaction with GSH. The following compounds were isolated and characterized by 1H NMR spectroscopy and determination of the pK values: 4-dimethylamino-2 (glutathione-S-yl)-phenol (2-GS-DMAP), 4-dimethylamino-3-(glutathione-S-yl) phenol (3-GS-DMAP), 4-dimethylamino-2,5-bis(glutathione-S-yl)-phenol (2,5-bis GS DMAP), 4-dimethylamino-2,6-bis(glutathione-S-yl)-phenol (2,6-bis GS-DMAP), and 4 dimethylamino-2,3,6-tris(glutathione-S-yl)-phenol (2,3,6-tris GS-DMAP). Ferrihemoglobin-forming activity was investigated with oxyhemoglobin, alkylated with N-ethylmaleimide (Hb-NES) to prevent binding of oxidized compounds to the protein SH groups. DMAP, 2,6-bis-GS-DMAP, and 2-GS-DMAP (0.1 mM each) completely oxidized Hb-NES (0.6 mM) in a decreasing order of activity (pH 7.4, 37 degrees C, air); the other derivatives were quite inactive. The same thioether reactivity was observed during autoxidation. Ferrihemoglobin formation by the reactive thioethers was greatly enhanced when the oxygen tension was increased from 2 to 100%. In contrast, variation of the oxygen tension had only marginal effects on the activity of DMAP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889836 TI - Additional pathways of S-conjugate formation during the interaction of thiols with nitrosoarenes bearing pi-donating substituents. AB - During the well-established reaction pathways of nitrosoarenes interacting with thiols, a reactive N-(thiol-S-yl)-arylamine cation was implicated in the so called rearrangement reaction which transforms the semimercaptal to the sulfinamide. In the case of nitrosoarenes with pi-donating substituents, this cationic transition state includes resonance structures bearing the positive charge in 2 and 4 position, thereby facilitating the attack of nucleophiles to the aromatic ring. Investigating the reaction products of 4-nitrosophenetol and reduced glutathione in chemical systems and human red cells, some glutatione S conjugates were detected other than the already known sulfenamide and sulfinamide. Three of them were separated by HPLC and identified by mass spectroscopy, 1H-NMR, and UV-visible spectroscopy, by determination of pKa values and chemical behavior. The hitherto unknown conjugates are 4-ethoxy-2 (glutathione-S-yl)-aniline, N-(4-ethoxyphenyl)-N'-(glutathione-S-yl) benzoquinonediimine, and 4-amino-4'-ethoxy-2-(glutathione-S-yl)-diphenylamine. In preliminary experiments, some of these conjugates were shown to be highly active in producing ferrihemoglobin. Considerations on the formation pathways of these metabolites lend further support to the electrophilic N-(glutathione-S yl)arylamine cation as a reactive intermediate that may be implicated in nitrosoarene toxicity. PMID- 7889837 TI - Synthetic and oxidative studies on 8-(arylamino)-2'-deoxyguanosine and -guanosine derivatives. AB - Facile aerial oxidation is a general feature of guanine ribo- and 2' deoxyribonucleosides that are substituted at the 8-position by an aminoaryl group. In previous work, it had been suggested that two of the major oxidation products are a pair of diastereomers having a spiro structure. These were presumed to be related by a chiral difference at the spiro carbon atom. The pattern of the oxidative process involves a contraction of the pyrimidine ring. It was thought to be analogous to that suggested by other investigators for the oxidation of uric acid, but for which no really definitive evidence had been presented. We have been able now to isolate in a crystalline state one of the diastereomers produced by the aerial oxidation of 8-phenylaminoguanosine under alkaline conditions. Analysis by X-ray diffraction has now confirmed the type of spiro structure promulgated previously. These findings also imply that spiro compounds are likely to be produced during the aerial oxidation of any 8 arylaminoguanine nucleoside or 2'-deoxynucleoside. In addition, this work adds considerable weight to the results of Poje and Sokolic-Maravic who proposed that a spiro intermediate is produced during the aerial oxidation of uric acid (12,13). However, they found this compound to be unstable to base, in contrast to the arylaminoguanine oxidation products. In the course of the above work we showed that the 8-arylamino derivatives of guanosine can be converted by the Barton deoxygenation method to the corresponding 2'-deoxyribonucleosides. This makes available a number of the latter compounds, which are not easily prepared by other methods. PMID- 7889838 TI - A selective synthesis of 4-aminobiphenyl-N2-deoxyguanosine adducts. AB - A selective synthesis of N2-deoxyguanosine adducts derived from 4-aminobiphenyl (ABP) is described. The reactions of O2-trifluoromethylsulfonyl-O6-allyl-3',5'-O bis(tert-butyldimethyl silyl)-2'- deoxyxanthosine with 3-amino-4 acetaminobiphenyl and 4-hydrazinobiphenyl, respectively, are the key steps. Successive removal of the protecting groups from the protected adducts leads to the free adducts 3-(deoxyguanosine-N2-yl)-acetyl-ABP and N-(deoxyguanosyl-N2-yl) ABP, respectively. PMID- 7889839 TI - Metabolic activation routes of arylamines and their genotoxic effects. AB - Two different types of DNA adducts are formed from many aromatic amines by bioactivation: N-acetylated and nonacetylated, arylamine DNA adducts. It has become clear from experiments using N-acetyl-2-aminofluorene and 2-aminofluorene adducts to C8 of deoxyguanosine that these two types of adducts may have different effects on DNA structure and DNA replication. We have determined blocking of DNA replication by various other N-acetylarylamine and arylamine deoxyguanosine adducts. It was found that the N-acetyl group in general is required for blocking of DNA replication; the nature of the aromatic moiety seems to be of minor importance. Little information is available on the genotoxic effects of these adducts in mammalian cells in vivo. We have tried to get more insight in this by investigating the clastogenicity, the initiation of preneoplastic cells, and the promotional effects of various aromatic amines from which different ratios of N-acetylarylamine DNA adducts to arylamine DNA adducts are formed in the rat liver. Our results show that formation of N-acetylarylamine adducts to C8 of deoxyguanosine in the liver is correlated with clastogenicity and hepatic promoting effect. Initiation capacities, however, seem to be correlated with formation of nonacetylated, arylamine adducts. Mechanisms by which formation of N-acetylarylamine DNA adducts may generate a promoting effect in the liver are discussed. PMID- 7889840 TI - DNA adduct measurements and tumor incidence during chronic carcinogen exposure in rodents. AB - In an attempt to elucidate the relationship between DNA adduct formation and tumorigenesis, DNA adducts were measured in the livers and bladders of mice during chronic exposure to several different doses of 2-acetylaminofluorene (2 AAF) and 4-aminobiphenyl (4-ABP). Continuous oral administration of these compounds for 4 weeks produced an increase in DNA adduct formation during the first 2 weeks, followed by a plateau, which presumably occurred because the rate of adduct removal offset the rate of adduct formation. The quantity of DNA adducts present at equilibrium correlated directly with the carcinogen concentration; therefore, when exposure was continued for 4 weeks, DNA adducts that reflected the plateau level at each dose could be expressed as a function of dose. Liver and bladder DNA adduct profiles thus obtained during administration of multiple doses of 2-AAF (to female mice) and 4-ABP (to male and female mice) were compared to profiles for tumor incidences obtained during lifetime exposures to the same doses. These experiments demonstrated similar profiles for DNA adduct formation and tumorigenesis in liver. In the bladder, DNA adducts were linear, but tumors only appeared at the higher doses in conjunction with cell proliferation. In addition to these aromatic amines, similar data are available for aflatoxin B1, diethylnitrosamine, and (methylnitrosamino)-1-(3-pyridyl)-1 butanone (also known as nicotine-derived nitrosoketone). Of the nine different biological situations (carcinogen/species/sex/organ) for which data are available, correlations between steady-state DNA adduct levels and tumorigenic response at the different doses were linear in five of the nine biological models.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889841 TI - DNA adducts in target and nontarget tissues of 3,2'-dimethyl-4-aminobiphenyl in rats. AB - 3,2'-Dimethyl-4-aminobiphenyl (DMAB) is a potent carcinogenic aromatic amine which demonstrates multiorgan tropism in rats. Using polyclonal antibodies against DMAB-DNA adducts, an immunohistochemical procedure as well as an ELISA were applied to investigate the relationship between DMAB-DNA adduct formation and tumorigenicity. Dose-related nuclear staining was observed 24 hr after application of the carcinogen but specificity in terms of sites of tumor development was lacking. No observable decrease in staining intensity was evident in most organs by 168 hr after administration of DMAB. Specific DNA lesions which could be responsible for carcinogenesis were not detected by the 32P-postlabeling method. The tumorigenic response of the ventral prostate in five strains of rats was roughly paralleled by DMAB-DNA adduct levels generated in the tissue. Strong enhancement of bladder tumor development by combined administration of the antioxidants, butylated hydroxyanisole, or butylated hydroxytoluene, with DMAB, was well correlated with an increase in DNA adducts. Our findings so far suggest that DNA adduct formation itself does not determine the carcinogenic organotropism of DMAB. Other factors (including cell proliferation and promotion by exogenous agents) may play important additional roles. For individual target organs or tissues, however, there seems to be a correlation between adduct levels and carcinogenic potential. PMID- 7889843 TI - The role of nongenotoxic mechanisms in arylamine carcinogenesis. AB - The growth of preneoplastic nodules during the feeding of a carcinogenic 2 acetylaminofluorene (2-AAF) regimen is preceded by several alterations in the physiologic homeostasis. Many of these alterations can be considered adaptive responses to the drug exposure. One property of AAF could be identified that clearly distinguishes this complete rat liver carcinogen from at least two other, incomplete rat liver carcinogens. Highly specific redox cycling in mitochondria was demonstrated in vitro, and this observation could well contribute an explanation of the morphologic and histochemical observations in vivo. It is emphasized that nongenotoxic effects may play an important role in the generation of tumors by genotoxic carcinogens. PMID- 7889842 TI - Molecular dosimetry of aromatic amines in human populations. AB - Certain aromatic amines carcinogenic for the human urinary bladder, such as 4 aminobiphenyl, undergo hepatic metabolic activation to N-hydroxylamines, which are transported to the bladder. During the transport process, these reactive species come in contact with hemoglobin and react with this blood protein. The principal hemoglobin adduct formed is a cysteine sulfinamide, and quantitative methods have been developed for the analysis of sulfinamide adducts at the levels present in ordinary human blood specimens. N-acetylation is an alternative metabolic fate to N-hydroxylation. The amount of hemoglobin adduct is decreased to the extent that this pathway is increased relative to N-hydroxylation. Thus, the hemoglobin adduct is sensitive to dose, cytochrome P-450-mediated activation, and N-acetyltransferase-mediated detoxification. In addition, it has been shown that DNA adduct concentration of 4-aminobiphenyl present in human bladder epithelial cells is significantly associated with hemoglobin adduct levels. Thus, the hemoglobin adduct of 4-aminobiphenyl, and perhaps several other aromatic amines, is a good dosimeter for the target tissue dose of the ultimate carcinogenic metabolite of these amines. Several studies have been undertaken in which the hemoglobin adducts of aminobiphenyls in human blood specimens were determined quantitatively. Information concerning exposure status and acetylator phenotype of the same individuals was obtained simultaneously. The results of these studies indicate that the hemoglobin adduct of 4-aminobiphenyl is closely associated with three major risk factors for bladder cancer: cigarette smoking, type of tobacco smoked, and acetylator phenotype. They also support a major etiologic role for aromatic amines in much of human bladder cancer. PMID- 7889844 TI - DNA adducts and carcinogenicity of nitro-polycyclic aromatic hydrocarbons. AB - We have been interested in the structure-activity relationships of nitro polycyclic aromatic hydrocarbons (nitro-PAHs), and have focused on the correlation of structural and electronic features with biological activities, including mutagenicity and tumorigenicity. In our studies, we have emphasized 1-, 2-, 3-, and 6-nitrobenzo[a]pyrenes (nitro-B[a]Ps) and related compounds, all of which are derived from the potent carcinogen benzo[a]pyrene. While 1-, 2-, and 3 nitro-B[a]P are potent mutagens in Salmonella, 6-nitro-B[a]P is a weak mutagen. In vitro metabolism of 1- and 3-nitro-B[a]P has been found to generate multiple pathways for mutagenic activation. The formation of the corresponding trans-7,8 dihydrodiols and 7,8,9,10-tetrahydrotetrols suggests that 1- and 3-nitro-B[a]P trans-7,8-diol-9,10-epoxides are ultimate metabolites of the parent nitro-B[a]Ps. We have isolated a DNA adduct from the reaction between 3-nitro-B[a]P trans-7,8 diol-anti9,10-epoxide and calf thymus DNA, and identified it as 10-(deoxyguanosin N2-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-3-ni tro-B[a]P . The same adduct was identified from in vitro metabolism of [3H]3-nitro-B[a]P by rat liver microsomes in the presence of calf thymus DNA. A DNA adduct of 3-nitro-B[a]P formed from reaction of N-hydroxy-3-amino-B[a]P, prepared in situ with calf thymus DNA was also isolated. This adduct was identified as 6-(deoxyguanosin-N2-yl)-3-amino B[a]P. The same adduct was obtained from incubating DNA with 3-nitro-B[a]P in the presence of the mammalian nitroeductase, xanthine oxidase, and hypoxanthine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889845 TI - Formation of DNA adducts and induction of mutations in rats treated with tumorigenic doses of 1,6-dinitropyrene. AB - 1,6-Dinitropyrene, a component of diesel exhaust, is a lung carcinogen in male F344 rats following a single intrapulmonary administration. In this study, rats were treated with tumorigenic doses of 1,6-dinitropyrene to establish dose response relationships for the formation of DNA adducts in target (lung) and nontarget (liver) tissues and for the induction of 6-thioguanine-resistant mutations in spleen T-lymphocytes. One week after treatment with 0.3, 1, 3, 10, 30, 100, or 150 micrograms of 1,6-dinitropyrene, dose-responsive DNA binding was measured in lung and liver with binding in the lung being 10-fold higher than in the liver. In the lung, a 2-fold increase in dose resulted in a 1.8-fold increase in DNA binding at treatments up to 30 micrograms of 1,6-dinitropyrene, while in the liver, a 2-fold increase in 1,6-dinitropyrene produced a 2-fold increase in DNA binding at doses up to the 10 micrograms treatment. Higher doses of 1,6 dinitropyrene resulted in proportionally smaller increases in adduct formation in the two tissues. When measured 21 weeks after treatment, mutations in T lymphocytes increased with doses up to 100 micrograms of 1,6-dinitropyrene, but the response was nonlinear throughout the dose range. These findings indicate that concentrations of 1,6-dinitropyrene that produce a dose-dependent induction of lung tumors also result in a dose-dependent formation of DNA adducts and induction of lymphocyte mutations but that the dose-response curves for DNA binding and mutations are different. PMID- 7889846 TI - The carcinogenicity of methoxyl derivatives of 4-aminoazobenzene: correlation between DNA adducts and genotoxicity. AB - To elucidate the cause of the difference in genotoxic activity between carcinogenic 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and noncarcinogenic 2 methoxy-4-aminoazobenzene (2-MeO-AAB), we analyzed DNA adducts in the livers of rats exposed to either of these chemicals and studied the resulting biologic potential with the aid of in vitro modified M13 phage DNA. 32P-Postalbeling analysis revealed that the carcinogen 3-MeO-AAB produced 20-fold higher amounts of adducts than did 2-MeO-AAB. Five adducts were formed in the 3-MeO-AAB case whereas only one adduct was apparent in 2-MeO-AAB-treated rat. Studies of in vitro DNA replication using N-hydroxy (N-OH)-aminoazo dye-modified M13 phage DNA as a template demonstrated inhibition by 3-MeO-AAB adducts to be substantially greater than in the 2-MeO-AAB-adducts. The specificity of mutagenesis induced in M13mp9 phage DNA by these chemicals also was analyzed after transfection into SOS induced Escherichia coli JM103, mutation frequencies being higher with N-OH-3-MeO AAB- than N-OH-2-MeO-AAB-modified DNA. The mutation spectra differed in each case. Our data suggest that the difference in hepatocarcinogenic activity between the two chemicals depends not only on qualitative and quantitative variation in adduct formation but also on conformation changes in modified DNA. PMID- 7889847 TI - Pathways for the mutagenesis of 1-nitropyrene and dinitropyrenes in the human hepatoma cell line HepG2. AB - The mutagenicity, metabolism, DNA adduction and induction of unscheduled DNA synthesis (UDS) of 1-nitropyrene and 1,8-dinitropyrene were investigated in the human hepatoma cell line HepG2. Previous results had demonstrated that 1 nitropyrene was both mutagenic at the hgprt locus and induced UDS in these cells. In the present study, we find that the dinitropyrenes, although highly mutagenic in Salmonella typhimurium, are not mutagenic and do not induce UDS in the HepG2. Although the rate of 1,8-dinitropyrene nitroreduction was less than that of 1 nitropyrene nitroreduction, this did not explain the lack of mutagenicity and UDS induction by the dinitropyrenes. Therefore, it is proposed that the arylhydroxylamine O-esterificase is not expressed in these cells. Since cytochrome P450-mediated C-oxidation is the predominant metabolic pathway in vivo, we sought to determine if an increase in the ratio of cytochrome P450 mediated C-oxidation over nitroreduction would result in increased or decreased DNA adducts in the HepG2. The administration of 2.5 microM 3-methylcholanthrene to the HepG2 increased the ratio of C-oxidation/nitroreduction from 2.8 +/- 1.9 to 50.4 +/- 46.1. This was accompanied by a decrease in the C8-guanyl adduct of 1 nitropyrene (via nitroreduction) from 18.7 +/- 7.0 to 4.8 +/- 1.7 fmoles/micrograms DNA, without any further increase in other 1-nitropyrene DNA adducts. These results suggest that the cytochrome P450-mediated metabolism of 1 nitropyrene to epoxides, phenols, and dihydrodiols is not an activation pathway in the HepG2 cells, and may explain the weak carcinogenicity of 1-nitropyrene in vivo, where cytochrome P450-mediated C-oxidation predominates. PMID- 7889848 TI - Mutagenic activity of heterocyclic amines in cooked foods. AB - Mutagenic heterocyclic amines are generated in foods when they are cooked at temperatures over 150 degrees C. These compounds are present from 0.1 to 50 ppb, depending on the food and cooking conditions. These heterocyclic amines are not only present in cooked red meat, fish, and chicken, but are also present at lower levels in baked and fried foods derived from grain. Mutagenicity of fried beef hamburgers cooked at 230 degrees C is 800 +/- 37 TA98 revertants per gram cooked weight. We measured 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx), 2 amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMelQx), and 2-amino-3 methylimidazo[4,5-f]quinoline (IQ) formation at this temperature and found 3.0 +/ 2.0, 1.0 +/- 0.18, and 0.06 +/- 0.03 ng/g, respectively. 2-amino-1-methyl-6 phenylimidaz[4,5-b]pyridine (PhIP) was found at a higher concentration of 9.6 ng/g. In our laboratory we have shown these heterocyclic amines are capable of producing both reverse and forward mutations in Salmonella bacteria and forward mutations in Chinese hamster ovary cells (CHO). We have also been able to show a statistically significant increase in mutations in the pancreas of the "mutamouse" following PhIP exposure. The pancreas also shows relatively high DNA binding compared to other organs in the mouse. The number and type of mutations depend on the repair capacity of the cells for both Salmonella and CHO. In Salmonella the mutations are primarily 2-base deletions when the cells lack uvrB repair, but mutations are more complex (larger deletions and insertions) but lower in frequency when repair is functional.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889849 TI - Gene activation studied by immunological methods. AB - Gene activation can be studied at several levels: transcription (mRNA), translation (proteins), or phenotypical alterations (functional activity or morphology). These levels can be studied in situ or biochemically by the use of specific probes for normal or altered DNA, mRNA, or proteins. Immunological probes are potent tools for studies of alterations induced by xenobiotics in target organs. When the effects of xenobiotics are studied in whole tissue, the cellular heterogeneity of the organ must be taken into account. For this reason, combined in situ and biochemical techniques are necessary. Antibodies to normal or altered cellular constituents are used for identification, quantitation, and cellular localization of proteins and modified DNA. Many xenobiotics alter gene activation by interactions with DNA. After activation, 2-acetylaminofluorene (AAF) forms DNA adducts, which can be identified immunologically. Combined with bromodeoxyuridine (BrdU) pulse labeling, techniques have been developed to demonstrate reduced adduct concentrations in proliferating cells and preneoplastic foci in the livers of AAF-fed rats. Carcinogen-induced DNA modifications are implicated as a major mechanism of altered gene activation in neoplasia, leading to phenotypical alterations. Also, cellular differentiation may be affected by xenobiotics. Differentiation-associated markers can be used for studies of gene activation. In mouse skin, the keratins K1 and K10 are only expressed in suprabasal, differentiating cells. BrdU pulse chase experiments combined with double immunofluorescence have revealed that K1 and K10 are sequentially turned on 18 to 24 hr after DNA synthesis and are followed by suprabasal migration. After a single application of the tumor promotor 12-O tetradecanoylphorbol-13-acetate (TPA), cell migration starts directly after mitosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889851 TI - Polymorphism of human acetyltransferases. AB - Acetylation by arylamine N-acetyltransferases (NATs) is a major route in the metabolism of numerous drugs and carcinogens. Recent studies suggest that the same enzymes also catalyze N,O-transacetylation and O-acetylation. A genetic polymorphism of clinical relevance divides the human population into slow and rapid acetylators of arylamines. Two human NATs, NAT1 and NAT2, have recently been characterized by protein purification, cloning, and functional expression of the respective genes; both were localized to chromosome 8. NAT1 codes for a protein with ubiquitous tissue distribution and a high affinity for p aminobenzoic acid and p-aminosalicylic acid, so-called monomorphic substrates. NAT2 codes for a protein predominantly expressed in liver with a high affinity for sulfamethazine and other polymorphically metabolized drugs. NAT2 was analyzed at the level of protein, RNA and DNA derived from phenotyped slow and rapid acetylators. Two common (M1, M2) and one rare (M3) mutant allele were identified and their mutations characterized. A simple polymerase chain reaction-based DNA test can identify > 95% of mutant alleles and predict the phenotype. PMID- 7889850 TI - Requirement for metabolic activation of acetylaminofluorene to induce multidrug gene expression. AB - Previously we have demonstrated that several xenobiotics can induce multidrug (mdr) gene expression in cultures of primary isolated hepatocytes. One of the best of these xenobiotic inducers in rat hepatocytes is 2-acetylaminofluorene (2 AAF), which induces mdr expression by an enhancement of mdr gene transcription. In all species studied to date, AAF is extensively and variously metabolized. In this study we have sought to determine if AAF per se or a metabolite is responsible for mediating the increase in mdr gene transcription and expression. This study demonstrates that AAF per se is not active, but that the effect of AAF we have observed on mdr gene transcription and expression in the rat is due to the formation of a reactive metabolite(s). Our data indicate that this reactive metabolite is probably N-acetoxy-2-aminofluorene or the sulfate ester of N hydroxy-AAF. The requirement for the formation of one of these metabolites may explain the differences in species response to AAF, in terms of mdr gene expression, that we have observed. We hypothesize that the mechanism by which mdr gene transcription is increased in response to AAF involves a covalent interaction between a reactive metabolite and an mdr gene regulatory protein. Our current work is concerned with the exploration of this hypothesis. PMID- 7889852 TI - Modification of plasmid and bacteriophage DNA by aromatic amines: effects on survival, template activity, and mutagenicity. AB - The carcinogenic and mutagenic effects of the aromatic amines are believed to depend on their covalent modification of DNA, primarily through the formation of adducts at C8 of guanine. The actual biologic and biochemical responses to these adducts can be envisioned as the consequence of the abilities of the cell to repair the lesions, with or without fidelity, and the introduction of errors through bypass of the adducts by polymerases. A key question is whether changes in DNA sequence arise through the participation of common repair processes that cause mutations independent of adduct structure. Alternatively, do mutations arise through miscoding during polymerase bypass at the site of the adducts and are, therefore, more likely to produce sequence changes that are more characteristic of adduct structure? This question has been approached using single, site-specific, or randomly introduced aromatic amine DNA adducts in bacterial cells, and in vitro studies with DNA polymerases that employ site specifically modified templates. The results of both approaches demonstrate that these adducts are distinguished readily by virtue of their structures, thus supporting the conclusion that mutagenic effects of the aromatic amines arise from their structures rather than from their triggering a common inaccurate repair response. PMID- 7889853 TI - Biological monitoring of exposure to 3-chloro-4-fluoroaniline by determination of a urinary metabolite and a hemoglobin adduct. AB - In two studies, involving 75 and 72 workers, potential exposure to 3-chloro-4 fluoroaniline (CFA) was biologically monitored by determination of its main urinary metabolite 2-amino-4-chloro-5-fluorophenol sulfate (CFA-S). As this method only allows the detection of recent exposure, analysis of CFA adducts bound to hemoglobin (Hb) was investigated as a method that allows biological monitoring of exposure to CFA over longer periods. The median CFA-S concentration in 67 samples from the first study was 0.14 mumole/g creatinine (range < 0.05 2.82) and in 201 samples from the second study 0.21 mumole/g creatinine (range < 0.05-6.05). In addition, urine samples, collected after shifts with supposed incidental exposure, slightly higher concentrations were measured: 0.27 mumole/g creatinine (range < 0.05-122; 18 samples) and 0.76 mumole/g creatinine (range < 0.05-18.5; 46 samples), respectively. The median Hb adduct concentration in 75 samples from the first study was 9 pmoles CFA/g Hb (range < 5-640) and in 46 samples from the second study 12 pmoles/g Hb (range 3-24). In 24 blood samples collected after incidents, a median concentration of 13 pmoles CFA/g Hb (range < 5-52) was found. Urinary CFA-S and Hb adducts correlated well in samples collected shortly after incidental exposures. However, in 25% of the operators, no CFA-S was detected during routine biological monitoring while Hb adduct analysis showed clear evidence of exposure. This indicates that because of the stability of Hb adducts of CFA in blood, intermittent exposure to CFA is more reliably biologically monitored by determination of Hb adducts of CFA than by assessment of urinary CFA-S. PMID- 7889854 TI - Molecular dosimetry of 2,4-difluoroaniline in humans and rats by determination of hemoglobin adducts. AB - Exposure to 2,4-difluoroaniline (DFA) was monitored by GC-MS of DFA adducts bound to hemoglobin (Hb). In two studies, involving 20 and 16 workers potentially exposed to low concentrations of DFA, median concentrations of 10 (range 1-83) and 20 (range 4-322) pmole/g Hb were found, respectively. For better interpretation of these results, the in vivo binding of DFA to Hb was investigated. DFA was administered orally at doses of 0, 0.078, 0.775, 7.75, and 77.5 mumole/kg/day, to 10 male and 10 female Fischer 344 rats for 10 consecutive days (2 rats/sex/dose group). A linear relation between dose and adduct concentration was observed. At the two lowest doses (0.078 and 0.775 mumole/kg/day) no methemoglobinemia was observed, but adducts could easily be measured. At these doses, the mean adduct levels were in the same range as found in the human studies. As yet, no occupational exposure limit for DFA has been established. The German biological tolerance value (BAT-value) for aniline was set at 7.2 nmole/g Hb. This BAT-value is based on the relation between methemoglobinemia and adduct formation. The amount of Hb binding by aniline and DFA was found to be similar in the rat. Assuming that this is also the case in humans, the BAT-value for aniline may tentatively be used for DFA as well. In both studies of occupationally exposed workers, the adduct levels were well below this BAT-value. PMID- 7889856 TI - Nitroreduction and formation of hemoglobin adducts in rats with a human intestinal microflora. AB - In the covalent binding of nitroarenes to macromolecules, nitroreduction is an important step. The intestinal microflora represents an enormous potential of bacterial nitroreductase activity. As a consequence, the in vivo nitroreduction of orally administered nitroarenes is primarily located in the intestine. In this study, we have investigated the nitroreduction of 2-nitrofluorene (2-NF) by a human microflora in female Wistar rats. Germ-free (GF) rats were equipped with a bacterial flora derived from human feces. Nontreated GF rats and GF animals equipped with a conventional rat flora were used as controls. The composition of the human and the conventional microflora isolated from the rats were consistent with the microflora of the administered feces. In the rats receiving only sunflower seed oil, no adducts were detected. The animals equipped with a human or rat microflora that received 2-aminofluorene (2-AF) formed 2-AF hemoglobin (Hb)-adducts at average levels (mean +/- SEM) of 5.3 +/- 0.3 and 6.7 +/- 0.7 mumole/g Hb, respectively. After 2-NF administration, the adduct levels were 0.022 +/- 0.003 and 0.043 +/- 0.010 mumole/g Hb, respectively. In the GF rats, an adduct level of 0.57 +/- 0.09 was determined after 2-AF administration and no adducts were detected after 2-NF administration. The results show that nitroreduction by an acquired human intestinal microflora and subsequent adduct formation can be studied in the rat in vivo. PMID- 7889855 TI - Development of methods to monitor exposure to 1-nitropyrene. AB - On the basis of 32P-postlabeling analysis, treatment of rats with 1-nitropyrene (1-NP) resulted in the formation of multiple DNA adducts in the liver, mammary glands, and peripheral lymphocytes. The one adduct resulting from nitroreduction, N-(deoxyguanosin-8-yl)-1-aminopyrene, constitutes only a minor component among the adducts. In the present study, incubation of calf thymus DNA with mutagenic ring-oxidized metabolites of 1-NP in vitro in the presence and absence of xanthine oxidase also resulted in the formation of multiple adducts. On the basis of their chromatographic behavior, it appears that DNA adducts derived from such metabolites may have been formed in vivo; however, this needs to be confirmed. [3H]1-NP was given to male and female F344 rats and Sprague-Dawley rats by gavage at five dose levels in the range of 0.1 to 1000 micrograms/kg bw. This led to stable hemoglobin adducts accounting for 0.08 +/- 0.05% of the dose (n = 3 rats). The radioactivity associated with hemoglobin following administration of [3H]1-NP was cleared with a half-life of about 14 days, which is faster than that of unmodified erythrocytes in the rat (t1/2 = 30 days). Treatment of the hemoglobin with 1% HCl in acetone, to precipitate the globin, released the radioactivity; it was all bound to the heme moiety. The structures of the heme adducts have not been elucidated; yet, because of their stability, they may be useful as dosimeters for human exposure to 1-NP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889857 TI - Hydrolyzable hemoglobin adducts of polyfunctional monocyclic N-substituted arenes as dosimeters of exposure and markers of metabolism. AB - Hemoglobin adducts of 10 polyfunctional amino- and nitro-substituted benzenes and toluenes were analyzed: 2,4,6-trinitrotoluene, 2,4- and 2,6-dinitrotoluene, 2 amino-4-nitrotoluene, 4-amino-2-nitrotoluene, 2,4- and 2,6-diaminotoluene, 1,3 dinitrobenzene, 1-amino-3-nitrobenzene, and 1,3-diaminobenzene. A single dose (0.5 mmole/kg) of the test compounds was administered to female Wistar rats by gavage, and blood extracted and hemoglobin prepared after 24 hr. One or more cleavage products could be obtained in each case by hydrolyzing hemoglobin (Hb). Hemoglobin binding indices (HBI: binding [mmole/mole Hb]/dose [mmole/kg]) and the ratios of hydrolyzable adducts were determined. The HBI ranged between < 0.02 and 69.0. The results indicate the in vivo formation of several, covalently bound, hydrolyzable hemoglobin adducts. Conclusions on prevailing metabolic pathways can be drawn. Total binding of several compounds seems sufficient for biomonitoring of human blood samples. These chemicals are considered representative for environmental contamination with explosives of this type, and we propose their Hb adducts be used as dosimeters for human exposure to these suspected carcinogens. PMID- 7889858 TI - Species differences in metabolism of heterocyclic aromatic amines, human exposure, and biomonitoring. AB - Heterocyclic aromatic amines (HAAs) are animal carcinogens and suspected human carcinogens which are formed in cooked foods at the low parts per billion level. HAAs in cooked meats were purified by either immunoaffinity chromatography or solid phase tandem extraction, which allowed for the simultaneous analysis of 11 HAAs by HPLC. The metabolism of two prominent HAAs, 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3-methylimidazo[4,5 f]quinoline (IQ), was investigated in animal models and in vitro with human tissues to develop strategies for human biomonitoring. MeIQx and IQ are rapidly absorbed from the gastrointestinal tract of rodents and transformed into several detoxification products which are excreted in urine and feces. Metabolites result from cytochrome P450-mediated ring oxidation at the C-5 position followed by conjugation to sulfate or beta-glucuronic acid. Other major metabolites include the phase II conjugates, N2-glucuronide and N2-sulfamate. A metastable N2 glucuronide conjugate of the genotoxic metabolite of N-hydroxy-MeIQx was also detected in urine and bile. The binding of both carcinogens to blood proteins was low and suggests that human biomonitoring through protein adducts may be difficult. These metabolic pathways exist in nonhuman primates and several of these pathways also occur in vitro with human liver. The urinary excretion of MeIQx in seven human subjects following consumption of cooked beef or fish ranged between 2 and 22 ng in 12 hr when determined by negative ion chemical ionization GC-MS. After acid hydrolysis of urine, the amount of MeIQx increased 4- to 10 fold in 6 of the 7 subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889859 TI - The role of fat and calcium in the production of foci of aberrant crypts in the colon of rats fed 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine. AB - The modulation by dietary fat levels of intestine carcinogenesis is well documented. New developments suggest that calcium ions may also play a role. A rapid bioassay, the induction of foci of aberrant crypts in the colon, was used to explore the interaction between dietary fat and calcium. Male F344 rats 6 weeks of age were placed on diets containing 5 or 20% corn oil, and 0.04 or 0.32% calcium ion, as calcium lactate. Each dietary group was fed 400 ppm 2-amino-1 methyl-6-phenylimidazo[4,5-b]pyridine (PhlP), and negative controls received the diets alone. A positive control group was given 2 mg N-nitrosomethylurea (NMU) intrarectally four times in a 2-week period. All rats were killed after 9 weeks. The intestinal tract was rinsed with Krebs-Ringer buffer. After staining a 6-cm segment of the descending colon and rectum with 0.2% methylene blue, foci of aberrant crypts were evaluated microscopically. With PhlP as a carcinogen, the rats on a high-fat, low-calcium level had more foci of aberrant crypts than animals on a low-fat level. With the higher calcium level, there were fewer foci and aberrant crypts, but the effect of fat was still significant. With NMU and a low-calcium level, the effect of fat level was evident. However, with the higher calcium intake, there were considerably more foci of aberrant crypts than on the low-calcium level, and the effect of the dietary fat level was not obvious.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889860 TI - Dietary modulation of DNA adduct formation of the food mutagen 2-amino-3 methylimidazo[4,5-f]quinoline in the male Fischer 344 rat. AB - In numerous in vivo systems it has been shown that diets high in menhaden oil (a fish oil high in omega-3 fatty acids) can inhibit the carcinogenic process. In the present study, we have assessed the effects of a diet containing menhaden oil on 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA adduct formation in target tissues of the male Fischer 344 rat. Young adult male Fischer 344 rats were maintained on either a) an AIN-76A diet containing 5% corn oil, b) an isocaloric AIN-76A diet modified to contain 2% corn oil and 19% menhaden oil (MO diet), or c) a regular laboratory rodent diet (chow diet) for 6 weeks prior to receiving a single oral dose of 10 or 50 mg IQ/kg. Groups of four animals were killed 1 or 6 days after IQ administration. Using 32P-postlabeling assays, IQ-DNA adducts were isolated and quantitated in the liver, small intestine, and large intestine. Adduct patterns were similar in all cases. Adduct levels, expressed as relative adduct labeling values (RAL x 10(7)), were related to dose in all three tissues, with liver levels up to 10-fold higher than the large intestine and up to 20-fold higher than the small intestine. On day one, liver adduct levels in animals on the AIN-76A diet were similar to those in animals on the chow diet, but those in animals on the MO diet were approximately 2-fold lower.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889861 TI - Hemoglobin binding of arylamines and nitroarenes: molecular dosimetry and quantitative structure-activity relationships. AB - N-Oxidation and nitroreduction to yield N-hydroxyarylamines are metabolic steps that are crucial for the genotoxic properties of aromatic amines and nitroarenes, respectively. N-Hydroxyarylamines can form adducts with DNA, tissue proteins, and the blood proteins albumin and hemoglobin in a dose-dependent manner. The determination of hemoglobin adducts is a useful tool for biomonitoring exposed populations. We have established the hemoglobin binding index (HBI) [(mmole compound/mole Hb)/(mmole compound/kg body weight)] of several aromatic amines and nitroarenes in female Wistar rats. Incorporating values obtained by other researchers in the same rat strain, the logarithm of hemoglobin binding (log HBI) was plotted against several physicochemical parameters and against calculated electronic descriptors of nitroarenes and arylamines. Most arylamines and nitroarenes form hydrolyzable (e.g., sulfinamide) adducts with hemoglobin in rats. The amount of hemoglobin binding decreases with the oxidizability of the arylamines, except for compounds that are substituted with halogens in ortho or meta position. For halogen-substituted arylamines, the amount of hemoglobin binding is directly proportional to the pKa. Hemoglobin binding of nitroarenes increases with the reducibility of the nitro group. The structure activity relationships (SAR) for hemoglobin binding of nitroarenes and arylamines are comparable. The SAR found for hemoglobin binding were compared with the SAR found in the literature for mutagenicity, carcinogenicity, and cytotoxicity of arylamines and nitroarenes. In general, the mutagenicity or carcinogenicity of arylamines increases with their oxidizability. This first set of data suggests that the levels of hemoglobin binding, mutagenicity, and carcinogenicity of arylamines are not determined by the same electronic properties of the compounds, or not by these properties alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889862 TI - Epidemiology of cancer from exposure to arylamines. AB - Occupational exposure to arylamines such as benzidine, 2-naphthylamine, and 4 aminobiphenyl is associated with exceptionally elevated risks of bladder cancer (up to 100-fold or more). In one plant, all 15 workers involved in distilling naphthylamine developed bladder cancer, suggesting that for high levels of exposure to potent carcinogens individual susceptibility is irrelevant. More recently, exposure to other arylamines also has been suggested to increase the risk of bladder cancer in humans. In addition, cohort and case-control studies suggest that several job titles or exposures may involve elevated risks of bladder cancer. Some of these jobs or exposures (such as in the aluminum industry) are associated with exposure to arylamines. Arylamines are found also in tobacco smoke, and different sources of evidence suggest that they can explain the risk of bladder cancer, which has been shown clearly in smokers. Epidemiologic analyses of timing of exposure in workers occupationally exposed to arylamines or in air-cured tobacco smokers suggest that arylamines exert both an early- and a late-stage activity, compatible with a two-mutation theory of bladder carcinogenesis. PMID- 7889863 TI - Peroxidative metabolism of carcinogenic N-arylhydroxamic acids: implications for tumorigenesis. AB - Peroxidative oxidations of chemical carcinogens including N-substituted aryl compounds could result in their metabolic activation because the products react with cellular molecules and lead to cytotoxicity, mutagenicity, and carcinogenicity. In vivo, peroxidative activities are chiefly of neutrophilic leukocyte origin. Neutrophils may be attracted to the site(s) of exposure to carcinogen and, via phagocytosis and respiratory burst, release oxidants that catalyze carcinogen activation and/or cause DNA damage. Our studies, presented herein, concern oxidations of carcinogenic N-arylhydroxamic acids, N-hydroxy-N-2 fluorenylacetamide (N-OH-2-FAA), and N-hydroxy-N-2-fluorenylbenzamide (N-OH-2 FBA), by enzymatic and chemical systems simulating those of neutrophils, myeloperoxidase and hydrogen peroxide (H2O2) +/- halide, and hypohalous acid and halide at the physiologic concentrations (0.1 M Cl- and/or 0.1 mM Br-) and the pH (4-6.5) of phagocytosis. Studies also concern oxidations of the hydroxamic acids by rat peritoneal neutrophils stimulated to undergo respiratory burst and release myeloperoxidase in medium-containing 0.14 M Cl- +/- 0.1 mM Br-. The metabolites formed in the presence of exogenous H2O2 are consistent with two peroxidative mechanisms: one electron-oxidation to a radical that dismutates to equimolar 2 nitrosofluorene (2-NOF) and the ester of the respective hydroxamic acid and halide-dependent oxidative cleavage, especially efficient in the presence of Br-, to equimolar 2-NOF and the respective acyl moiety. 2-NOF and the esters undergo further enzymatic and nonenzymatic conversions to unreactive products and/or may bind to cellular macromolecules. The results suggest that peroxidative metabolism of N-arylhydroxamic acids by neutrophils, yielding the potent direct mutagen 2 NOF and the electrophilic esters, occurs in vivo and is involved in the activation and thus local tumorigenicities of the hydroxamic acids at the site(s) of application. PMID- 7889865 TI - Characterization of rat hepatic acetyltransferase. AB - Rat liver cytosol is capable of N-acetylation (NAT) of arylamines, O-acetylation (OAT) of arylhydroxylamines, and N,O-acetyltransfer (AHAT) of arylhydroxamic acids. Physical, enzymatic, and immunochemical techniques now support the conclusion that a single 32 kDa protein accounts for all of these activities. Of the five immunoglobulin (IgG1) mouse monoclonal antibodies (mAb) produced against this protein, each affected one or more of these acetylation activities. When mixed with rat hepatic cytosol and then chromatographed on a gel filtration column, mAbs 1F2 and 5F8 increased the apparent size of all enzymes capable of acetylation from 32 kDa to the exclusion volume. Each of the mAbs reacted with only a single 32 kDa protein on SDS-PAGE/Western blots, regardless of the state of purity of the enzyme. This enzyme is unstable in low salt solutions, as reflected by a relative loss in NAT versus AHAT activity, but it does not result in changes in either molecular weight or isoelectric point (pl). A second form of instability is shown by the formation of more basic peptides with pls as high as 6, again without change in molecular weight. Although NAT activity is retained in acetyltransferase (AT) that has a minimally modified pl, further increases in pl result in total loss of enzyme activity. The differential effects of the mAbs on AT suggest that the ratios of NAT, OAT, and AHAT may be highly dependent on the conformation of the enzyme and, consequently, provide insight as to why the abilities of ATs from different species exhibit such dissimilar potentials for the activation of aromatic amines by OAT and AHAT. PMID- 7889864 TI - N-hydroxyarylamine O-acetyltransferase of Salmonella typhimurium: proposal for a common catalytic mechanism of arylamine acetyltransferase enzymes. AB - Acetyl-CoA:N-hydroxyarylamine O-acetyltransferase is an enzyme involved in the metabolic activation of N-hydroxyarylamines derived from mutagenic and carcinogenic aromatic amines and nitroarenes. The O-acetyltransferase gene of Salmonella typhimurium has been cloned, and new Ames tester substrains highly sensitive to mutagenic aromatic amines and nitroarenes have been established in our laboratory. The nucleotide sequence of the O-acetyltransferase gene was determined. There was an open reading frame of 843 nucleotides coding for a protein with a calculated molecular weight of 32,177, which was close to the molecular weight of the O-acetyltransferase protein determined by using the maxicell technique. Only the residue of Cys69 in O-acetyltransferase of S. typhimurium and its corresponding residue (Cys68) in N-acetyltransferase of higher organisms were conserved in all acetyltransferase enzymes sequenced so far. The amino acid sequence Arg-Gly-Gly-X-Cys, including the Cys69, was highly conserved. A mutant O-acetyltransferase of S. typhimurium, which contained Ala69 instead of Cys69, no longer showed the activities of O- and N-acetyltransferase. These results suggest that the Cys69 of S. typhimurium and the corresponding cysteine residues of the higher organisms are essential for the enzyme activities as an acetyl-CoA binding site. We propose a new catalytic model of acetyltransferase for S. typhimurium and the higher organisms. PMID- 7889866 TI - Arylamines suppress their own activation and that of nitroarenes in V79 Chinese hamster cells by competing for acetyltransferases. AB - The effect of 2-aminofluorene (2-AF) on the toxicity of 2-aminoanthracene (2-AA) and 1,6-dinitropyrene (1,6-DNP) was studied in N-acetyltransferase-proficient V79 NHr1A2 cells genetically engineered for the expression of cytochrome P4501A2, and in wild-type V79-NH cells. 2-AA inhibited the growth of V79-NHr1A2 cells and induced the formation of micronuclei at concentrations of 0.1 to 1.0 microM, but was virtually without toxic effects at a concentration of 10 microM. Addition of 2-AF protected against the cytotoxic and genotoxic effects elicited by low concentrations of 2-AA. Half-maximum protection was observed at 0.2 to 0.5 microM 2-AF. The arylamine also prevented the cytotoxicity caused by 1,6-DNP in V79-NH cells and completely suppressed the formation of 1-acetylamino-6-nitropyrene from 1,6-DNP in these cells. The results indicate that arylamines and related N hydroxyarylamines are substrates for the same acetyltransferase in V79-NH cells. In consequence, arylamines are capable of suppressing the activation of their proximate cytotoxic and genotoxic products in these cells and, presumably, in vivo. PMID- 7889868 TI - International Symposium on the Health Effects of Boron and its Compounds. Proceedings. Irvine, California, September 16-17, 1992. PMID- 7889867 TI - Characterization and expression of hepatic sulfotransferase involved in the metabolism of N-substituted aryl compounds. AB - An aryl sulfotransferase, whose cDNA was isolated from the rat liver library, was found to catalyze bioactivation of minoxidil through N-O-sulfation and N sulfation of a carcinogenic heterocyclic amine, IQ, by expression in COS-1 cells. cDNA of a human ortholog also was isolated and characterized as a major minoxidil activating enzyme in human liver. Another group of aryl sulfotransferases catalyzing O-sulfation of carcinogenic N-hydroxyarylamines was separated from livers of rats and humans. These sulfotransferases have been shown to possess similar functional properties and also to relate immunochemically with each other. Current understanding on the primary structure of these sulfotransferases also is discussed. PMID- 7889869 TI - The developmental toxicity of boric acid in mice, rats, and rabbits. AB - Boric acid (BA) is a naturally occurring agent used in manufacturing processes and numerous consumer products. Because of the potential for both industrial and consumer exposure to boron-containing compounds, and the lack of developmental toxicity data, the National Toxicology Program evaluated the potential for boric acid to cause developmental toxicity in pregnant Swiss (CD-1) mice, Sprague Dawley rats (n = 26-28/group), and New Zealand rabbits (n = 18-23/group). BA was provided in the feed to mice and rats at 0, 0.1, 0.2, or 0.4% throughout gestation to attain steady-state exposure as early as possible during development. Average doses (mg/kg/day) were 248, 452, or 1003 for mice, and 78, 163, or 330 in rats. A separate group of rats received 0.8% BA in the feed, or 539 mg/kg/day only on gestation days (gd) 6 to 15. Rabbits were given BA (0, 62.5, 125, or 250 mg/kg) by gavage administration on gd 6 to 19. Maternal body weight, food and/or water consumption and signs of toxicity were monitored at regular intervals. At termination, gd 17 (mice), 20 (rats), or 30 (rabbits), the uterus was examined to determine the number of resorptions, dead, or live fetuses. Fetuses were weighed and live fetuses were examined for external, visceral, and skeletal defects. Mouse dams exhibited mild renal lesions (> or = 248 mg/kg/day BA), increased water intake and relative kidney weight (1003 mg/kg/day BA), and decreased weight gain during treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889870 TI - Chemical disposition of boron in animals and humans. AB - Elemental boron was isolated in 1808. It typically occurs in nature as borates hydrated with varying amounts of water. Important compounds are boric acid and borax. Boron compounds are also used in the production of metals, enamels, and glasses. In trace amounts, boron is essential for the growth of many plants, and is found in animal and human tissues at low concentrations. Poisoning in humans has been reported as the result of accidental ingestion or use of large amounts in the treatment of burns. Boron as boric acid is fairly rapidly absorbed and excreted from the body via urine. The half-life of boric acid in humans is on the order of 1 day. Boron does not appear to accumulate in soft tissues of animals, but does accumulate in bone. Normal levels of boron in soft tissues, urine, and blood generally range from less than 0.05 ppm to no more than 10 ppm. In poisoning incidents, the amount of boric acid in brain and liver tissue has been reported to be as high as 2000 ppm. Recent studies at the National Institute of Environmental Health Sciences have indicated that boron may contribute to reduced fertility in male rodents fed 9000 ppm of boric acid in feed. Within a few days, boron levels in blood and most soft tissues quickly reached a plateau of about 15 ppm. Boron in bone did not appear to plateau, reaching 47 ppm after 7 days on the diet. Cessation of exposure to dietary boron resulted in a rapid drop in bone boron.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889872 TI - Reproductive effects of inorganic borates on male employees: birth rate assessment. AB - The purpose of this study was to investigate the potential for reproductive effects of inorganic borate compounds on male employees. The standardized birth ratio (SBR) methodology was used to assess fertility among male employees, using live births as the measured end point. The ratio of female to male births was also assessed. Data were collected via questionnaires and telephone follow-up interviews. Medical insurance records were assessed for nonresponders. Exposures were assessed using three semiquantitative categories. We found a statistically significant increase in fertility as measured by live births among the employees of the inorganic borate facility. There does not appear to be any decrease in fertility due to exposures either as analyzed by the borate exposure categories or over time, which is an indirect measure of exposures. We found a nonstatistically significant increase in the percentage of female offspring. This increase was due, not to a deficiency of male offspring, but rather to a marked increase in the numbers of female offspring. This increase in percentage female offspring does not appear to be related to exposures to inorganic borates. Based on the data, exposures to inorganic borates do not appear to adversely affect fertility in this population. PMID- 7889871 TI - Acute and chronic respiratory effects of sodium borate particulate exposures. AB - This study examined work-related chronic abnormality in pulmonary function and work-related acute irritant symptoms associated with exposure to borate dust in mining and processing operations. Chronic effects were examined by pulmonary function at the beginning and end of a 7-year interval. Time-specific estimates of sodium borate particulate exposures were used to estimate cumulative exposure during the study interval. Change in pulmonary function over the 7 years was found unrelated to the estimate of cumulative exposure during that interval. Exposure-response associations also were examined with respect to short-term peak exposures and incidence of five symptoms of acute respiratory irritation. Hourly measures of health outcome and continuous measures of particulate exposure were made on each subject throughout the day. Whenever a subject reported one of the irritant symptoms, a symptom intensity score was also recorded along with the approximate time of onset. The findings indicated that exposure-response relationships were present for each of the specific symptoms at several symptom intensity levels. The associations were present when exposure was estimated by both day-long and short-term (15-min) time-weighted average exposures. Associations persisted after taking account of smoking, age, and the presence of a common cold. No significant difference in response rate was found between workers exposed to different types of sodium borate dusts. PMID- 7889873 TI - Use of inductively coupled plasma-mass spectrometry in boron-10 stable isotope experiments with plants, rats, and humans. AB - The commercial availability of inductively coupled plasma-mass spectrometry technology (ICP-MS) has presented the opportunity to measure the boron concentrations and isotope ratios in a large number of samples with minimal sample preparation. A typical analytical sequence for fecal samples consists of 25 acid blanks, 1 digestion blank, 5 calibration solutions, 4 standard reference material solutions, 10 samples, and 4 natural abundance bias standards. Boron detection limits (3 x 1 sigma) for acid blanks are 0.11 ppb for 10B, and 0.40 ppb for 11B. Isotope ratios were measured in fecal samples with 20 to 50 ppb boron with < 2% relative standard deviation. Rapid washout and minimal memory effects were observed for a 50 ppb beryllium internal standard, but a 200 ppb boron biological sample had a 1.0 ppb boron memory after a 6-min washout. Boron isotope ratios in geological materials are highly variable; apparently this variability is reflected in plants of a fixed natural abundance value for boron requires that a natural abundance ratio be determined for each sample or related data set. The natural abundance variability also prevents quantitation and calculation of isotope dilution by instrument-supplied software. To measure boron transport in animal systems, 20 micrograms of 10B were fed to a fasted rat. During the 3 days after a 10B oral dose, 95% of the 10B was recovered from the urine and 4% from the feces. Urinary isotope ratios, 11B/10B, changed from a natural abundance of 4.1140 to an enriched value of 0.95077, a 77% change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889874 TI - The relationship of blood- and urine-boron to boron exposure in borax-workers and usefulness of urine-boron as an exposure marker. AB - Daily dietary-boron intake and on-the-job inspired boron were compared with blood and urine-boron concentrations in workers engaged in packaging and shipping borax. Fourteen workers handling borax at jobs of low, medium, and high dust exposures were sampled throughout full shifts for 5 consecutive days each. Airborne borax concentrations ranged from means of 3.3 mg/m3 to 18 mg/m3, measured gravimetrically. End-of-shift mean blood-boron concentrations ranged from 0.11 to 0.26 microgram/g; end-of-shift mean urine concentrations ranged from 3.16 to 10.72 micrograms/mg creatinine. Creatinine measures were used to adjust for differences in urine-specific gravity such that 1 ml of urine contains approximately 1 mg creatinine. There was no progressive increase in end-of-shift blood- or urine-boron concentrations across the days of the week. Urine testing done at the end of the work shift gave a somewhat better estimate of borate exposure than did blood testing, was sampled more easily, and was analytically less difficult to perform. Personal air samplers of two types were used: one, the 37-mm closed-face, two-piece cassette to estimate total dust and the other, the Institute of Occupational Medicine (IOM) sampler to estimate inspirable particulate mass. Under the conditions of this study, the IOM air sampler more nearly estimated human exposure as measured by blood- and urine-boron levels than did the sampler that measured total dust.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889875 TI - Summary: International Symposium on the Health Effects of Boron and its Compounds. PMID- 7889876 TI - Hypolipidemic, anti-obesity, anti-inflammatory, anti-osteoporotic, and anti neoplastic properties of amine carboxyboranes. AB - The amine-carboxyborane derivatives were shown to be effective antineoplastic/cytotoxic agents with selective activity against single-cell and solid tumors derived from murine and human leukemias, lymphomas, sarcomas, and carcinomas. The agents inhibited DNA and RNA synthesis in preference to protein synthesis in L1210 lymphoid leukemia cells. Inosine-monophosphate dehydrogenase apparently is a target site of the compounds; similar effects on phosphoribosyl pyrophosphate amido transferase, orotidine-monophosphate decarboxylase, and both nucleoside and nucleotide kinases were observed. Deoxyribonucleotide pool levels were reduced in the cells; DNA strand scission was observed with the agents. In rodents, the amine carboxyboranes were potent hypolipidemic agents, lowering both serum cholesterol and triglyceride concentrations, in addition to lowering cholesterol content of very low-density lipoprotein and low-density lipoprotein (LDL) and elevating high-density lipoprotein (HDL) cholesterol concentrations. De novo regulatory enzymes involved in lipid synthesis were also inhibited (e.g., hypocholesterolemic 3-hydroxy-3-methyl-Coenzyme A reductase, acyl-Coenzyme A cholesterol acyltransferase, and sn-glycerol-3-phosphate acyltransferase). Concurrently, the agents modulated LDL and HDL receptor binding, internalization, and degradation, so that less cholesterol was delivered to the plaques and more broken down from esters and conducted to the liver for biliary excretion. Tissue lipids in the aorta wall of the rat were reduced and fewer atherosclerotic morphologic lesions were present in quail aortas after treatment with the agents. Cholesterol resorption from the rat intestine was reduced in the presence of drug. Genetic hyperlipidemic mice demonstrated the same types of reduction after treatment with the agents. The agents would effectively lower lipids in tissue based on the inhibition of regulatory enzymes in pigs. These findings should help improve domestic meat supplies from fowl and pigs. The amine-carboxyboranes were effective anti-inflammatory agents against septic shock, induced edema, pleurisy, and chronic arthritis at 2.5 to 8 mg/kg. Lysosomal and proteolytic enzyme activities were also inhibited. More significantly, the agents were dual inhibitors of prostaglandin cyclooxygenase and 5'-lipoxygenase activities. These compounds also affected cytokine release and white cell migration. Subsequent studies showed that the amine-carboxyboranes were potent anti-osteoporotic agents reducing calcium resorption as well as increasing calcium and proline incorporation into mouse pup calvaria and rat UMR-106 collagen. PMID- 7889877 TI - Proposed physiologic functions of boron in plants pertinent to animal and human metabolism. AB - Boron has been recognized since 1923 as an essential micronutrient element for higher plants. Over the years, many roles for boron in plants have been proposed, including functions in sugar transport, cell wall synthesis and lignification, cell wall structure, carbohydrate metabolism, RNA metabolism, respiration, indole acetic acid metabolism, phenol metabolism and membrane transport. However, the mechanism of boron involvement in each case remains unclear. Recent work has focused on two major plant-cell components: cell walls and membranes. In both, boron could play a structural role by bridging hydroxyl groups. In membranes, it could also be involved in ion transport and redox reactions by stimulating enzymes like nicotinamide adenine dinucleotide and reduced (NADH) oxidase. There is a very narrow window between the levels of boron required by and toxic to plants. The mechanisms of boron toxicity are also unknown. In nitrogen-fixing leguminous plants, foliarly applied boron causes up to a 1000% increase in the concentration of allantoic acid in leaves. In vitro studies show that boron inhibits the manganese-dependent allantoate amidohydrolase, and foliar application of manganese prior to application of boron eliminates allantoic acid accumulation in leaves. Interaction between borate and divalent cations like manganese may alter metabolic pathways, which could explain why higher concentrations of boron can be toxic to plants. PMID- 7889878 TI - The biochemical effects of physiologic amounts of dietary boron in animal nutrition models. AB - This review summarizes evidence that supports working hypotheses for the roles of boron in animal model systems. It is well established that vascular plants, diatoms, and some species of marine algal flagellates have acquired an absolute requirement for boron, although the primary role of boron in plants remains unknown. Recent research findings suggest that physiologic amounts of supplemental dietary boron (PSB) affect a wide range of metabolic parameters in the chick and rat model systems. Much of the current interest in boron animal nutrition began with the initial finding that PSB stimulates growth in cholecalciferol (vitamin D3)-deficient chicks, but does not markedly affect growth in chicks receiving adequate vitamin D3 nutriture. The finding suggests that boron affects some aspect of vitamin D3 metabolism or is synergistic with vitamin D3 in influencing growth. Vitamin D3 regulates energy substrate utilization, and current research findings indicate that dietary boron modifies that regulatory function. The concentration of circulating glucose, the most thoroughly investigated metabolite to date, responds to PSB, especially during concomitant vitamin D3 deficiency. In chicks, PSB substantially alleviated or corrected vitamin D3 deficiency-induced elevations in plasma glucose concentrations. The influence of vitamin D3 on cartilage and bone mineralization is mediated in part through its role as a regulator of energy substrate utilization; calcification is an energy-intensive process. There is considerable evidence that dietary boron alleviates perturbations in mineral metabolism that are characteristic of vitamin D3 deficiency. In rachitic chicks, PSB alleviated distortion of the marrow sprouts of the proximal tibial epiphysial plate, a distortion characteristic of vitamin D3 deficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889879 TI - Effect of dietary boron on the aging process. AB - Total boron concentrations in Drosophila changed during development and aging. The highest concentration of boron was found during the egg stage, followed by a decline during the larval stages. Newly emerged flies contained 35.5 ppm boron. During the adult stage the boron concentration increased by 52% by 9 weeks of age. Adding excess dietary boron during the adult stage decreased the median life span by 69% at 0.01 M sodium borate and by 21% at 0.001 M sodium borate. Lower concentrations gave small but significant increases in life span. Supplementing a very low boron diet with 0.00025 M sodium borate improved life span by 9.5%. The boron contents of young and old mouse tissues were similar to those of Drosophila and human samples. Boron supplements of 4.3 and 21.6 ppm in the drinking water, however, did not significantly change the life span of old mice fed a diet containing 31.1 ppm boron. PMID- 7889880 TI - Relation of boron to the composition and mechanical properties of bone. AB - A review of the experimental studies relating boron to biological effects on appendicular and axial bones in animal models suggests that numerous influences, known and unknown, affect the responsiveness of bone to dietary boron. Degrees of skeletal response to boron are modified by other nutritional variables that include calcium, magnesium, vitamin D, and fluoride. Evidence suggests that appendicular and axial bones may differ in their responses. Tests of the mechanical properties of bones may provide useful criteria for assessing the impacts of boron status on bone. These tests might resolve questions about optimal intakes of boron because mechanical properties sometimes respond to boron when composition of bones does not. Difficulty in interpreting some of the existing research arises because of the incipient state of knowledge regarding boron nutriture, to analytical problems associated with determining accurately the small quantities of boron in feed and tissues, and to technological difficulties in controlling extraneous exposure of experimental animals to boron. Yet there is considerable evidence that both compositional and functional properties of bone are affected by boron status. PMID- 7889881 TI - An introduction to boron: history, sources, uses, and chemistry. AB - Following a brief overview of the terrestrial distribution of boron in rocks, soil, and water, the history of the discovery, early utilization, and geologic origin of borate minerals is summarized. Modern uses of borate-mineral concentrates, borax, boric acid, and other refined products include glass, fiberglass, washing products, alloys and metals, fertilizers, wood treatments, insecticides, and microbiocides. The chemistry of boron is reviewed from the point of view of its possible health effects. It is concluded that boron probably is complexed with hydroxylated species in biologic systems, and that inhibition and stimulation of enzyme and coenzymes are pivotal in its mode of action. PMID- 7889882 TI - Effects of dietary boron in rats fed a vitamin D-deficient diet. AB - Although boron has long been known to be a required nutrient for plants, it was not until recently that there was any suggestion of a nutritional requirement for animals and humans. Addition of boron to the diet of vitamin D-deficient chicks indicated that boron may play a role in animal nutrition. Studies with rats have demonstrated that supplemental dietary boron has most marked effects when the diet is deficient in known nutrients. We observed higher apparent-balance values of calcium, magnesium, and phosphorus for rats fed a vitamin D-deprived diet with dietary supplemental boron (2.72 ppm), than for rats fed the same diet without added boron (0.16 ppm). The treatment group with dietary supplemental boron demonstrated a high degree of variability in response to boron. We hypothesize that relatively large and variable vitamin D stores in weanling rats from a colony supplemented with 3000 IU vitamin D/kg diet accounted for the observed variable response. A recent, unpublished study using weanling rats from a low vitamin D colony appears to support this hypothesis. PMID- 7889883 TI - Biochemical and physiologic consequences of boron deprivation in humans. AB - Boron deprivation experiments with humans have yielded some persuasive findings for the hypothesis that boron is an essential nutrient. In the first nutritional study with humans involving boron, 12 postmenopausal women first were fed a diet that provided 0.25 mg boron/2000 kcal for 119 days, and then were fed the same diet with a boron supplement of 3 mg boron/day for 48 days. The boron supplementation reduced the total plasma concentration of calcium and the urinary excretions of calcium and magnesium, and elevated the serum concentrations of 17 beta-estradiol and testosterone. This study was followed by one in which five men over the age of 45, four postmenopausal women, and five postmenopausal women on estrogen therapy were fed a boron-low diet (0.23 mg/2000 kcal) for 63 days, then fed the same diet supplemented with 3 mg boron/day for 49 days. The diet was low in magnesium (115 mg/2000 kcal) and marginally adequate in copper (1.6 mg/2000 kcal) throughout the study. This experiment found higher erythrocyte superoxide dismutase, serum enzymatic ceruloplasmin, and plasma copper during boron repletion than boron depletion. The design of the most recent experiment was the same as the second study, except this time the diet was adequate in magnesium and copper. Estrogen therapy increased plasma copper and serum 17 beta-estradiol concentrations; the increases were depressed by boron deprivation. Estrogen ingestion also increased serum immunoreactive ceruloplasmin and erythrocyte superoxide dismutase; these variables also were higher during boron repletion than depletion for all subjects, not just those ingesting estrogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889884 TI - Dietary boron, brain function, and cognitive performance. AB - Although the trace element boron has yet to be recognized as an essential nutrient for humans, recent data from animal and human studies suggest that boron may be important for mineral metabolism and membrane function. To investigate further the functional role of boron, brain electrophysiology and cognitive performance were assessed in response to dietary manipulation of boron (approximately 0.25 versus approximately 3.25 mg boron/2000 kcal/day) in three studies with healthy older men and women. Within-subject designs were used to assess functional responses in all studies. Spectral analysis of electroencephalographic data showed effects of dietary boron in two of the three studies. When the low boron intake was compared to the high intake, there was a significant (p < 0.05) increase in the proportion of low-frequency activity, and a decrease in the proportion of higher-frequency activity, an effect often observed in response to general malnutrition and heavy metal toxicity. Performance (e.g., response time) on various cognitive and psychomotor tasks also showed an effect of dietary boron. When contrasted with the high boron intake, low dietary boron resulted in significantly poorer performance (p < 0.05) on tasks emphasizing manual dexterity (studies II and III); eye-hand coordination (study II); attention (all studies); perception (study III); encoding and short term memory (all studies); and long-term memory (study I). Collectively, the data from these three studies indicate that boron may play a role in human brain function and cognitive performance, and provide additional evidence that boron is an essential nutrient for humans. PMID- 7889885 TI - Plasma boron and the effects of boron supplementation in males. AB - Recently, a proliferation of athletic supplements has been marketed touting boron as an ergogenic aid capable of increasing testosterone. The effect of boron supplementation was investigated in male bodybuilders. Ten male bodybuilders (aged 20 to 26) were given a 2.5-mg boron supplement, while nine male bodybuilders (aged 21 to 27) were given a placebo for 7 weeks. Plasma total and free testosterone, plasma boron, lean body mass, and strength measurements were determined on day 1 and day 49 of the study. A microwave digestion procedure followed by inductively coupled argon plasma spectroscopy was used for boron determination. Twelve subjects had boron values at or above the detection limit with median value of 25 ng/ml (16 ng/ml lower quartile and 33 ng/ml upper quartile). Of the ten subjects receiving boron supplements, six had an increase in their plasma boron. Analysis of variance indicated no significant effect of boron supplementation on any of the other dependent variables. Both groups demonstrated significant increases in total testosterone (p < 0.01), lean body mass (p < 0.01), and one repetition maximum (RM) squat (p < 0.001) and one RM bench press (p < 0.01). The findings suggest that 7 weeks of bodybuilding can increase total testosterone, lean body mass, and strength in lesser-trained bodybuilders, but boron supplementation affects these variables not at all. PMID- 7889887 TI - Essentiality of boron for healthy bones and joints. AB - Since 1963, evidence has accumulated that suggests boron is a safe and effective treatment for some forms of arthritis. The initial evidence was that boron supplementation alleviated arthritic pain and discomfort of the author. This was followed by findings from numerous other observations epidemiologic and controlled animal and human experiments. These findings included a) analytical evidence of lower boron concentrations in femur heads, bones, and synovial fluid from people with arthritis than from those without this disorder; b) observation evidence that bones of patients using boron supplements are much harder to cut than those of patients not using supplements; c) epidemiologic evidence that in areas of the world where boron intakes usually are 1.0 mg or less/day the estimated incidence of arthritis ranges from 20 to 70%, whereas in areas of the world where boron intakes are usually 3 to 10 mg, the estimated incidence of arthritis ranges from 0 to 10%; d) experimental evidence that rats with induced arthritis benefit from orally or intraperitoneally administered boron; e) experimental evidence from a double-blind placebo-boron supplementation trial with 20 subjects with osteoarthritis. A significant favorable response to a 6 mg boron/day supplement was obtained; 50% of subjects receiving the supplement improved compared to only 10% receiving the placebo. The preceding data indicate that boron is an essential nutrient for healthy bones and joints, and that further research into the use of boron for the treatment or prevention of arthritis is warranted. PMID- 7889886 TI - Effects of boron supplementation on bone mineral density and dietary, blood, and urinary calcium, phosphorus, magnesium, and boron in female athletes. AB - The effects of boron supplementation on blood and urinary minerals were studied in female college students--17 athletes and 11 sedentary controls--over a one year period. The athletes had lower percent body fat and higher aerobic capacities than sedentary controls. Athletic subjects consumed more boron in their normal diets than sedentary subjects; all other dietary measures were similar between the two groups. The athletes showed a slight increase in bone mineral density, whereas the sedentary group showed a slight decrease. Serum phosphorus concentrations were lower in boron-supplemented subjects than in subjects receiving placebos, and were lower at the end of the study period than during baseline analysis. Activity depressed changes in serum phosphorus in boron supplemented subjects. Serum magnesium concentrations were greatest in the sedentary controls whose diets were supplemented with boron, and increased with time in all subjects. A group x supplement interaction was observed with serum magnesium; exercise in boron-supplemented subjects lowered serum magnesium. In all subjects, calcium excretion increased over time; in boron-supplemented subjects, boron excretion increased over time. In all subjects, boron supplementation affected serum phosphorus and magnesium, and the excretion of urinary boron. PMID- 7889888 TI - The reproductive toxicity of boric acid. AB - Previous studies on the reproductive toxicity of boric acid have indicated that male rodents suffer testicular atrophy after treatment. There were, however, no studies of the potential effects on female fertility or on the neonate. In addition, no study described the development of the testicular lesion, thought to be related to the mechanism of toxicity. A Reproductive Assessment by Continuous Breeding (RACB) study using mice exposed to boric acid at 1000, 4500, and 9000 ppm in the diet indicated that there are probably multiple sites of action, although male fertility appears very sensitive. Possible effects on female fertility cannot be separated from potential developmental toxicity and need additional investigation. Decrements in sperm motility were observed at all exposure levels, and testicular atrophy was confirmed in high- and middle-dose group males. This was investigated further by timed serial-sacrifice studies using 9000 ppm in the diet of rats, which found that the first lesion seen in the testis was an inhibition of spermiation (release of mature spermatids). With continued dosing, this was followed by a disorganization of the normal ordered layering of the seminiferous epithelium, germ cell sloughing and death, and finally, atrophy. Subsequent studies using additional doses (2000, 3000, 4500, 6000, and 9000 ppm) found that it was possible to observe inhibited spermiation that did not progress to atrophy (4500 ppm and below) within the 9-week exposure period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889889 TI - Toxicity and carcinogenicity studies of boric acid in male and female B6C3F1 mice. AB - Toxicity and potential carcinogenicity studies of boric acid were investigated in mice to verify in a second rodent species that this was a noncarcinogenic chemical. Earlier chronic studies in rats indicated boric acid was not a carcinogen. The chemical is nominated for testing because over 200 tons are produced annually, there are multiple uses for the product, and there is potential for widespread human exposure, both orally and dermally. Both sexes of B6C3F1 mice were offered diets mixed with boric acid for 14 days, 13 weeks, or 2 years. Dietary doses used in the acute, 14-day study were 0, 0.62, 1.25, 2.5, 5, and 10%; those in the subchronic, 13-week study were 0, 0.12, 0.25, 0.50, 1, and 2%; and doses in the 2-year, chronic study were 0, 0.25, and 0.50% in the diet. Mortality, clinical signs of toxicity, estimates of food consumption, body weight gain, and histopathologic examination of selected tissues constituted the variables measured. In the 14-day study mortality was proportional to dose and time of exposure in both sexes, occurring in dose groups as low as 2.5% and as early as 7 days of exposure. Body weights were depressed more than 10% below controls in the higher dose groups of both sexes. Mortality in the 13-week study was confined to the two highest dose groups in male mice and to the 2%-dose group in females. Body weight depression from 8 to 23% below those of controls occurred in the 0.50% and higher dose groups of both sexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889890 TI - Mechanism of the testicular toxicity of boric acid in rats: in vivo and in vitro studies. AB - High-dose boric acid (BA) exposure produces testicular lesions in adult rats characterized by inhibited spermiation (IS) that may progress to atrophy. In vivo and in vitro studies addressed possible mechanisms. In vivo, boron tissue disposition was examined, since no detailed data existed, and relevant boron concentrations for in vitro studies needed to be set. Since BA induces riboflavinuria and also affects calcium/phosphorus homeostasis, and testis zinc appears essential for normal testis function, we examined BA effects on flavin status and testis levels of phosphorus (P), calcium (Ca) and zinc (Zn). Data showed that the testicular toxicity and central nervous system (CNS) hormonal effect were not due to selective boron accumulation in testis or brain/hypothalamus, with testis boron concentrations at approximately 1 to 2 mM; that riboflavin deficiency is not involved, due to both the absence of overt signs of deficiency and effects on tissue flavin content during BA exposure; and that changes in testis P, Ca and Zn levels did not precede atrophy, and are therefore unlikely to be mechanistically relevant. In vitro studies addressed the hallmarks of the BA testicular toxicity: the mild hormone effect, the initial IS, and atrophy. No effect of BA on the steroidogenic function of isolated Leydig cells was observed, supporting the contention of a CNS-mediated rather than a direct hormone effect. Since increased testicular cyclic adenosine monophosphate (cAMP) produces IS, and a role for the serine proteases plasminogen activators (PAs) in spermiation has been proposed, we examined in vitro BA effects on both Sertoli cell cAMP accumulation and PA activity, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889891 TI - Calcium nutrition and its implications for osteoporosis. Part II. After menopause. PMID- 7889892 TI - Polyunsaturated fatty acids of the n-6 and n-3 series: effects on postprandial lipid and apolipoprotein levels in healthy men. AB - OBJECTIVE: The present study was carried out to determine effects of test meals of different fatty acid compositions on postprandial lipoprotein and apolipoprotein metabolism. DESIGN: The study was a randomized, single blind design. SETTING: The study was carried out in the Clinical Investigation Unit of the Royal Surrey County Hospital. SUBJECTS: Twelve male normal subjects with an average age of 22.4 +/- 1.4 years (mean +/- SD) were selected from the student population of the University of Surrey; one subject dropped out of the study because he found the test meal unpalatable. INTERVENTIONS: The subjects were given three evening test meals on three separate occasions, in which the oils used were either a mixed oil (rich in saturated fatty acids and approximated the fatty acid intake of the current UK diet), corn oil (rich in n-6 fatty acids), or fish oil (rich in n-3 fatty acids) 40 g of the oil under investigation were incorporated into a rice-based test meal. Triacylglycerol-rich lipoproteins triacylglycerol (TRL-TAG), TRL-cholesterol (TRL-cholesterol), plasma-TAG, plasma cholesterol (T-C), and serum apolipoprotein A-I and B (apo A-I and B) responses were measured. Postprandial responses were followed for 11 h. RESULTS: Postprandial plasma-TAG responses, calculated as incremental areas under the response curves (IAUC) were significantly reduced following the fish oil meal [365.5 +/- 145.4 mmol/l x min (mean +/- SD)[ compared with the mixed oil meal (552.0 +/- 141.7 mmol/l x min) (P < 0.05) and there was a strong trend towards the same direction in the TRL-TAG responses. In all instances, plasma-and TRL-TAG showed a biphasic response with increased concentrations occurring at 1h and between 3 and 7h postprandially. TRL-cholesterol, T-C, and serum apo A-I and B responses to the three meals were similar. CONCLUSIONS: The findings support the view that fish oils decrease postprandial lipaemia and this may be an important aspect of their beneficial effects in reducing risk of coronary heart disease (CHD). Further work is required to determine the mechanisms responsible for this effect. PMID- 7889893 TI - Postprandial lipoprotein lipase, insulin and gastric inhibitory polypeptide responses to test meals of different fatty acid composition: comparison of saturated, n-6 and n-3 polyunsaturated fatty acids. AB - OBJECTIVE: The present study was carried out to investigate effects of meals, rich in either saturated fatty acids (SFA), or n-6 or n-3 fatty acids, on postprandial plasma lipid and hormone concentrations as well as post-heparin plasma lipoprotein lipase (LPL) activity. DESIGN: The study was a randomized single-blind study comparing responses to three test meals. SETTING: The volunteers attended the Clinical Investigation Unit of the Royal Surrey County Hospital on three separate occasions in order to consume the meals. SUBJECTS: Twelve male volunteers with an average age of 22.5 +/- 1.4 years (mean +/- SD), were selected from the University of Surrey student population; one subject dropped out of the study because he found the test meal unpalatable. INTERVENTIONS: Three meals were given in the early evening and postprandial responses were followed overnight for 11h. The oils used to prepare each of the three test meals were: a mixed oil rich in saturated fatty acids (SFA) which mimicked the fatty acid composition of the current UK diet, corn oil, rich in n-6 fatty acids and a fish oil concentrate (MaxEPA) rich in n-3 fatty acids. The oil under investigation (40 g) was incorporated into the test meals which were otherwise identical [208 g carbohydrates, 35 g protein, 5.65 MJ (1350 kcal) energy]. Postprandial plasma triacylglycerol (TAG), gastric inhibitory polypeptide (GIP), and insulin responses, as well as post-heparin LPL activity (measured at 12 h postprandially only) were investigated. RESULTS: Fatty acids of the n-3 series significantly reduced plasma TAG responses compared to the mixed oil meal (P < 0.05) and increased post-heparin LPL activity 15 min after the injection of heparin (P < 0.01). A biphasic response was observed in TAG, with peak responses occurring at 1 h and between 3-7 h postprandially. GIP and insulin showed similar responses to the three test meals and no significant differences were observed. CONCLUSION: We conclude that fish oils can decrease postprandial plasma TAG levels partly through an increase in post-heparin LPL activity, which however, is not due to increased GIP or insulin concentrations. PMID- 7889895 TI - The incorporation of n-3 polyunsaturated fatty acids into plasma lipid and lipoprotein fractions in the postprandial phase in healthy volunteers. AB - OBJECTIVE: To examine the movement of long-chain polyunsaturated n-3 fatty acids across plasma lipoprotein fractions in the postprandial phase. DESIGN: Eight healthy volunteers ingested a test meal (% energy: protein 11, carbohydrate 16, fat 73) after an overnight fast where fish oil provided the sole fat source. Blood samples were taken at baseline and at hourly intervals thereafter for 12 h. Blood lipoprotein fractions were separated and analysed for triacylglycerol fatty acid compositions. These were also determined in non-esterified fatty acid and phospholipid fractions. RESULTS: All n-3 polyunsaturated fatty acids accumulated in all plasma lipoprotein fractions and in non-esterified fatty acids. The ratios of concentrations of docosahexaenoic acid (DHA) to eicosahexaenoic acid (EHA) were higher in chylomicrons (1.4 +/- 0.4) than in very low density lipoproteins (0.9 +/- 0.5) and particularly higher than in the non-esterified fatty acid fractions (0.8 +/- 0.4). The level of eicosapentaenoic acid (EPA) rose significantly in plasma phospholipids while that of docosahexaenoic acid (DHA) did not. CONCLUSIONS: All n-3 polyunsaturated fatty acids are rapidly incorporated into all plasma lipid fractions with the exception of uptake of DHA into plasma phospholipids. There is a clear tendency for EPA and DHA to partition differently into the different plasma lipid fractions. PMID- 7889894 TI - Effects of a new fish oil concentrate on plasma lipids and lipoproteins in patients with hypertriglyceridaemia. AB - OBJECTIVES: The effect of a fish oil preparation, K-85, in which the omega-3 fatty acid content was concentrated to 92% of total fat, on serum lipid and lipoprotein concentrations was investigated in patients with primary hypertriglyceridaemia. DESIGN: The study was a randomized, double-blind, placebo controlled study. SETTING: Seven centres participated in the study, five secondary referral centres and two general practices. SUBJECTS: Men and women aged 18-70 years with fasting serum triglyceride concentrations between 2 and 10 mmol/l and fasting serum cholesterol concentrations > 5.2 mmol/l were studied. Patients with diabetes mellitus, hypothyroidism, serious illness in the previous 3 months or severe concurrent illness were excluded from the study, as were drug or alcohol abusers and pregnant and lactating women. Ninety-five subjects entered the study, 79 completed the study. INTERVENTIONS: Patients were randomized to receive K-85 2 g twice daily or corn oil 2 g twice daily for 14 weeks. MAIN OUTCOME MEASUREMENTS: The serum concentrations of triglycerides and cholesterol, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipoprotein (a). Fasting blood glucose and blood pressure. RESULTS: Serum triglycerides and VLDL-cholesterol were significantly lower in the group treated with K-85 than in the placebo group after 6, 10 and 14 weeks (all P < 0.01) and there was a decrease in the serum triglyceride concentration from 3.99 (2.94-9.47) to 2.87 (1.2-9.93) mmol/l (P < 0.001) and in VLDL-cholesterol from 1.47 (0.77-3.63) to 1.12 (0.21-3.67) mmol/l (P < 0.01) in patients receiving K-85. Serum HDL-cholesterol increased from 0.98 (0.95-1.01) to 1.11 (1.07-1.15) mmol/l (P < 0.01) in the patients with type IV hyperlipoproteinaemia but did not change in those with type IIb. Serum LDL-cholesterol, lipoprotein (a) and fasting blood glucose were unaffected by K-85. Diastolic blood pressure decreased from 86 +/- 11 to 80 +/- 12 mmHg (P < 0.02) and was also lower than in the placebo group (P < 0.05). The corn oil placebo did not affect any of the parameters. CONCLUSION: K-85 is effective in lowering serum triglycerides and VLDL in patients with primary hypertriglyceridaemia and may have utility as a triglyceride-lowering agent. PMID- 7889896 TI - Long-stay versus short-stay hospital treatment of children suffering from severe protein-energy malnutrition. AB - OBJECTIVE: To contrast early discharge versus attempted full nutritional rehabilitation in hospital of children suffering from severe protein-energy malnutrition (PEM). DESIGN: Field experiment, two-way analysis of variance with one between group (short- versus long-stay) and one repeated measures factor (admission, then 12, 18, 24, 30 and 36 months post-admission). Covariates introduced. SETTING: Primary health care, Kingston, Jamaica. SUBJECTS: n = 81; mean age 11 months; 79 contribute longitudinal data; 44 every measurement. INTERVENTIONS: When concurrent illnesses had been treated and normal feeding re established (weight gain 5 g/kg.day-1), subjects were randomly allocated to short stay (SS) or long-stay (LS) group. LS retained in hospital for full nutritional rehabilitation mean 40 days). SS discharged immediately (mean 18 days) for standard Health Service care at home for 6 months plus high-energy supplement (3.31 MJ with 20.6 g protein daily) for first 3 months. After discharge LS received 6 months home care, but without supplementation. RESULTS: Significant advantages for LS group on NCHS weight & length for age at discharge, and at 12, 18, 24 and for length also 30 months (P < 0.05 to P < 0.001). Weight advantage peaked at 12 and 18 months, length later at 18 and 24 months. CONCLUSIONS: Contrary to earlier reports, full nutritional rehabilitation can be achieved in hospital for children suffering from PEM. Although in the long-term both groups move towards expected levels in their home community, a significant advantage maintained for approximately 2 years is developmentally advantageous during the critical time after weaning. PMID- 7889897 TI - The value of arm circumference measurements in assessing chronic energy deficiency in Third World adults. AB - OBJECTIVE: To assess the usefulness of mid-upper arm circumference (MUAC) as a substitute for body mass index (BMI: kg/m2) or an additional measure of adult nutritional state. DESIGN: Variously sampled adults aged 18-60 years from selected regions of five African countries, India, China and Papua New Guinea were measured. SUBJECTS: 2421 men and 3248 women were measured for their heights, weights and MUAC. Of these, 1569 men and 1905 women also had their triceps skinfold thickness measured, thus allowing additional estimates of muscle area circumferences and fat areas in the arm. RESULTS: MUAC and BMI were highly correlated in each national group; each group's MUAC differed from the overall mean MUAC at any BMI value by < 10%. Women's MUACs were smaller than men's at equivalent BMIs. Increases in MUAC with age were statistically significant but trivial. Muscle and fat measurements showed similar increases with BMI; a larger muscle mass in men explained their greater MUACs but muscle differences alone did not explain national variations in MUAC. The -1 SD MUAC value, taken as an independent measure of peripheral tissue wasting, readily distinguished those with a BMI < 16.0 from those with a BMI > 18.5; intermediate grades of BMI were poorly specified by MUAC values. CONCLUSION: MUAC values of 23.0 cm in men and 22.0 cm in women are useful cut-off points for simple screening of nutritional state. In combination with BMI it may provide a more refined classification of CED. This new combined classification scheme may be a better means of discriminating the at-risk underweight adults from those who are thin but not at risk. PMID- 7889898 TI - Effects of fish oil and vitamin E supplementation on copper-catalysed oxidation of human low density lipoprotein in vitro. AB - Eleven men received a fish oil (2.4 g n-3 fatty acids), fish oil plus vitamin E (300 IU) or no supplement for 3 weeks. Dietary fish oil increased the maximum amount of conjugated dienes formed during copper-catalysed oxidation of LDL in vitro by 18-20%. Fish oil also tended to decrease the lagtime before onset of oxidation, but this effect was counteracted by vitamin E. We conclude that fish oil supplementation increases the oxidizability of LDL in vitro, and vitamin E increases its oxidation resistance. PMID- 7889899 TI - The Ziggy theorem: toward an outcomes-focused health psychology. AB - The purpose of health care is twofold: to make people live longer and to enhance quality of life in the years before death. These goals are consistent with a Ziggy cartoon that emphasized that the meaning of life was "doin' stuff." "Doin' stuff" requires being alive (survival) and having the capability to perform activities. These objectives are quantifiable and can be represented in indices that combine life expectancy with health-related quality of life. This article emphasizes patient-oriented outcomes as a focal point for health care. This outcomes orientation is referred to as the Ziggy theorem. Examples demonstrate that emphasis on patient-oriented outcomes may redirect conceptualizations of public health indicators and may change the way medical subspecialists make clinical decisions. Furthermore, the Ziggy Theorem may suggest new approaches to the allocation of public health resources. PMID- 7889900 TI - Self-presentation can be hazardous to your health: impression management and health risk. AB - People's concerns with how others perceive and evaluate them can lead to behaviors that increase the risk of illness and injury. This article reviews evidence that self-presentation motives play a role in several health problems, including HIV infection; skin cancer; malnutrition and eating disorders; alcohol, tobacco, and drug use; injuries and accidental death; failure to exercise; and acne. The implications of a self-presentational perspective for research in health psychology, the promotion of healthful behaviors, and health care delivery are discussed. PMID- 7889901 TI - A multidimensional measurement model for cardiovascular reactivity: stability and cross-validation in two adult samples. AB - The factor structure for measures of stress-related cardiovascular reactivity was examined in 2 samples: a university campus employee sample (N = 72) and a sample of young adult twins (N = 113). In both samples, 5 noninvasive cardiovascular measures were monitored during a series of challenging laboratory tasks. We developed a 2-factor model depicting vascular and cardiac influences on responding. With confirmatory factor analysis, this model was shown to be consistent with the data across both samples, across 2 testing sessions, and across 2 sets of tasks. Latent variables measuring cardiac and vascular reactivity were highly reliable on retest as well. Individual differences in cardiovascular reactivity to mental stress may be characterized by a stable, 2 dimensional pattern of response. PMID- 7889902 TI - Effect of stress on perceived intoxication and the blood alcohol curve in men and women. AB - To determine the influence of stress on intoxication and blood alcohol concentration (BAC) 60 healthy male and female volunteers were exposed to a cold pressor test, distressing film, or control condition after consuming a moderate dose of alcohol. Two measures of perceived intoxication suggested a sobering effect of acute stressors. In addition, Ss viewing the distressing film showed longer latency to peak BAC than Ss in the control condition. As BAC began to fall, the cold pressor test initially increased rate of alcohol elimination. These stress-induced changes in intoxication and the BAC curve support a biobehavioral model in which stress may increase alcohol use partly because it attenuates alcohol's psychopharmacological impact. PMID- 7889903 TI - Role of hostility in women's health during midlife: a longitudinal study. AB - Relationships between hostility at ages 21, 27, 43, and 52 years old and general health at age 52 were investigated in a longitudinal sample of educated midlife women. Hostility was assessed at ages 21 and 27 using the Cook-Medley Hostility Scale (HO), and at all four test sessions using a California Psychological Inventory (CPI) derived hostility scale consisting of 33 CPI items that were either duplicates or close equivalents of HO items. Hostility at each age was negatively correlated with general health at age 52. Further analyses revealed that hostility at each age remained a significant health predictor at age 52 when possible mediator variables at age 43 (cigarette smoking, excessive alcohol intake, body mass index, negative life events, and social role satisfactions) were controlled. PMID- 7889904 TI - Perceived competencies, peer group affiliation, and risk behavior among early adolescents. AB - This study examined the role of self-esteem and peer group membership in risk behavior among 183 8th graders in a multiethnic school. The hypothesis was that domain-specific rather than global self-esteem would be associated with "crowd" membership that in turn would be related to risk behavior. Data were gathered through informant interviews and individual surveys. Domain-specific self-esteem was related to crowd affiliation as well as to alcohol and cigarette use; global self-esteem was not related. Crowd affiliation related to alcohol use and sexual behavior after controlling for the effects of demographic and self-esteem variables, but crowd membership did not fully mediate the relationship between self-esteem and risk behavior. Availability of alcohol and cigarettes mediated the relationship between crowd affiliation and use of these substances. Findings support growing evidence that multiple adolescent peer groups exist and that group membership is closely tied to behavior. PMID- 7889905 TI - When mom or dad has cancer: markers of psychological distress in cancer patients, spouses, and children. AB - This study assessed anxiety/depression and stress response symptoms in adult cancer patients (n = 117), spouses (n = 76), and their children (n = 110, ages 6 to 30 years old) near the patients' diagnoses to identify family members at risk for psychological maladjustment. Patients' and family members' distress was related to appraisals of the seriousness and stressfulness of the cancer but not related to objective characteristics of the disease. Patients and spouses did not differ in anxiety/depression or in stress-response symptoms. Both stress-response and anxiety/depression symptoms differed in children as a function of age, sex of child, and sex of patient. Adolescent girls whose mothers had cancer were the most significantly distressed. Implications for understanding the impact of cancer on the family are highlighted. PMID- 7889906 TI - Smoking at home: the impact of smoking cessation on nonsmokers' exposure to environmental tobacco smoke. AB - Nonsmokers who live with smokers are at increased risk for chronic disease. This study evaluated the impact of eliminating smoking in the home on nonsmokers' environmental tobacco smoke (ETS) exposure. Nonsmokers participated in measurements of their ETS exposure before and after the smoker in their home quit smoking. A matched comparison group of nonsmokers from nonsmoking homes was also included. ETS exposure was assessed using passive nicotine monitors, an exposure diary, and a questionnaire. Nonsmokers from smoking homes had significantly higher exposure to ETS than those from nonsmoking homes. There was a 60% reduction in nicotine levels following smoking cessation by the household smoker. However, there were still detectable levels of nicotine measured at posttest. These results have important implications for individual risk reduction and public health policy. PMID- 7889907 TI - Predictors of survival among hemodialysis patients: effect of perceived family support. AB - The authors examined the role of perceived family support and symptoms of depression as predictors of survival in a sample of 78 in-center hemodialysis patients. Cox regression analysis revealed significant effects for family support (p < .005), blood urea nitrogen (p < .01), and age (p < .005). The effect for depression was not significant. The Cox model indicated that a 1-point increase on the family support measure was associated with a 13% reduction in the hazard rate (i.e., mortality). Estimated 5-year mortality rates among low family support patients were approximately 3 times higher than estimated mortality for high support patients. Differences in patient adherence to the dietary and medication regimens failed to explain the significant effect of family support. PMID- 7889908 TI - Increasing screening mammography in asymptomatic women: evaluation of a second generation, theory-based program. AB - Two theory-based programs to increase mammography screening rates among asymptomatic women were implemented and evaluated in the community. One program (E) was based on the Health Belief Model (HBM); the second program (EP) added exercises adapted from the social psychology of compliance. Program impact on screening among 295 primarily Caucasian, middle-class women was evaluated against untreated controls (C) over a 6-month period. Both programs led to increases in HBM components (Perceived Susceptibility, and Perceived Benefits) and Intentions to obtain a mammogram. Screening rates 2 to 3 times higher were observed in the EP and E over C conditions; EP and E did not differ. A mediational model of compliance illustrated the interplay of HBM components in the compliance process. PMID- 7889909 TI - Predictors of cancer progression in young adult men and women: avoidance, intrusive thoughts, and psychological symptoms. AB - Psychological symptoms, avoidance, and intrusive thoughts were examined prospectively as predictors of cancer progression over a period of 1 year. Sixty six male and female cancer patients who differed in their diagnoses and initial disease-severity ratings participated. Measures of psychological factors, disease severity, and type of treatment were obtained near time of diagnosis and disease status (no cancer, continued or recurrent cancer, or deceased) 1 year later. Cross-sectional analyses near the time of diagnosis showed that initial psychological variables were intercorrelated with one another but unrelated to initial disease prognosis. Longitudinal findings revealed that, after controlling for initial disease parameters and age, avoidance predicted disease status 1 year later; however, neither psychological symptoms nor intrusive thoughts and emotions accounted for additional variance in disease outcomes. PMID- 7889910 TI - A test of the AIDS risk reduction model: psychosocial correlates of condom use in the AMEN cohort survey. AB - We examined the AIDS Risk Reduction Model (J. Catania, S. Kegeles, & T. Coates) in a sample of unmarried heterosexual adults with an HIV risk factor (n = 716). Labeling one's sexual behavior as risky was associated with having a history of sexually transmitted diseases, particularly genital herpes, and fewer stereotypic health beliefs. For people with secondary sexual partners, greater condom commitment was related to increased labeling, supportive condom norms, and greater enjoyment, and high levels of condom use were related to greater condom commitment, supportive norms, greater enjoyment, and health protective sexual communication. For people with primary partners, greater condom commitment was correlated with increased supportive condom norms, greater enjoyment, and having genital herpes, and high levels of condom use were correlated with greater condom commitment, greater enjoyment, and health protective sexual communication. PMID- 7889911 TI - An analysis of a behavioral intervention for children undergoing venipuncture. AB - An examination of factors was conducted to determine the effectiveness of the distraction component of a behavioral intervention (use of a party blower). In one condition, parents were instructed to coach children in the use of a party blower and to praise child cooperation. In a second condition, nurses were instructed to assist parents in coaching the child. Parents used the coaching skills they learned and got their children to use the distraction technique. Use of the distraction technique was associated with less crying. Encouragement from a health care professional and intervention early in the procedure did not enhance the intervention's effectiveness. Older children and children who were less distressed during the initial phase of the procedure were less likely to reject the intervention. PMID- 7889912 TI - EIPH: the case for capillary stress failure. PMID- 7889913 TI - The aetiopathogenesis of infectious keratitis in the horse. PMID- 7889914 TI - The role of biomechanics research in the understanding of equine lameness. PMID- 7889915 TI - Another fence jumped in the EHV-1 stakes. PMID- 7889916 TI - Stress failure of pulmonary capillaries as a mechanism for exercise induced pulmonary haemorrhage in the horse. AB - Exercise induced pulmonary haemorrhage (EIPH) is a serious problem in the Thoroughbred industry. The condition apparently occurs essentially in all Thoroughbreds in training but the mechanism has proved elusive. There is now strong evidence that the condition is caused by mechanical failure of the walls of the pulmonary capillaries when the pressure inside them rises to very high levels. It is well known that pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently we have shown that the wall stresses are very large when the capillary transmural pressure is raised, and in anesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mmHg and above. The incidence of stress failure is greatly increased at high lung volumes; and many of the ultrastructural changes are rapidly reversible when the capillary pressure is reduced. The principal forces acting on the capillary have been analysed. The strength of the thin part of the capillary wall can be attributed to the Type IV collagen in the extracellular matrix. The pulmonary vascular pressures of galloping Thoroughbreds reach very high levels. Mean pulmonary artery and left atrial pressures of up to 120 and 70 mmHg respectively have been directly measured with indwelling catheters. The reason for the high pulmonary vascular pressures is that these animals have been selectively bred over hundreds of years to run at great speeds over short distances and their maximal oxygen consumptions are very high. As a consequence, cardiac outputs are substantial, and the left ventricle needs very high filling pressures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889917 TI - Histological findings in corneal stromal abscesses of 11 horses: correlation with cultures and cytology. AB - Histopathology was compared to culture results and cytology from horses with corneal stromal abscess at the Auburn University and the Ohio State University Veterinary Teaching Hospitals. Significant bacteria were not isolated in culture or seen on histopathology in any of the horses. Although most bacteria infecting equine corneas can be isolated with blood and MacConkey's agars, failure to detect bacterial growth may not rule out infection because anaerobic or intracellular bacteria would not be isolated. The inability to visualise bacterial organisms on histological sections did not rule out their presence in the tissue, because there is often destruction of bacteria by neutrophils, macrophages and antibiotic therapy greatly reducing their numbers. Fungal keratitis was diagnosed by histopathology in 4 of 11 eyes (36%) and keratitis with no aetiological agent in 7 of 11 eyes (64%). Nine of 11 horses (82%) had a prominent neutrophilic stromal infiltrate and 2 (18%) had a predominantly pyogranulomatous reaction. Two of the 4 lesions that showed histological evidence of fungal infection were positive for identifiable fungi on culture and cytology. Fungal cultures of the other 2 cases with histological evidence of mycotic keratitis were negative or grew unidentifiable fungi which were considered pathogenic because, on histopathological sections, fungal hyphae were found deep in the corneal stroma surrounded by an inflammatory reaction. In 3 of 6 cases where fungi were recovered on culture, they were considered contaminants based on lack of evidence of organisms in histopathological sections. Histopathology and the use of special stains were important in the interpretation of culture and cytology results. PMID- 7889918 TI - In vitro mechanical properties of the accessory ligament of the deep digital flexor tendon in horses in relation to age. AB - The material properties of the accessory ligament of the deep digital flexor tendon (AL) of 21 forelimbs from horses between ages one day and 15 years were determined. The force (634-11416 N), failure stress (45-138 N/mm2), failure strain (7-24%) and tangent modulus (33-1639 MPa) are presented in relation to age. Tangent modulus did not indicate changes in elasticity due to age. The results demonstrate that complete ligament failures (CLF) of ALs of older horses (mean 7835 N) occur at lower forces than ALs of young adult horses (mean 8894 N). Sudden decreases, 'dips', in the force-time curves were noticed in ligaments from foals and yearlings and in ligaments from horses > 10 years. They were interpreted as the failure of a number of fibres which either fail at lower forces or are subject to higher forces than the rest. These differences in mechanical properties could be the result of age related differences in the material properties of ALs of older horses similar to alterations in collagenous tissue in other species. When analysing the data of the proximal, middle and distal regions of the ligaments separately, higher strain and elasticity were found in the distal compared to the proximal parts. It is suggested that the clinical occurrence of desmitis of the AL of older horses could be due to fibrillar failure caused by differences in the material properties of the ligaments. PMID- 7889919 TI - The cross-sectional areas of normal equine digital flexor tendons determined ultrasonographically. AB - Fifty-two animals, comprising 22 Irish Draught crosses (Group A), 15 Thoroughbreds (Group B) and 15 ponies (Group C) were examined ultrasonographically using a 7.5 mHz linear array probe and stand-off pad. All animals were free of tendon disease as determined from clinical and ultrasonographical examination. The superficial (SDFT) and deep (DDFT) digital flexor tendons were scanned at 7 transverse (axial) levels between the carpus and metacarpophalangeal joint. Each transverse image was digitised using a commercially available frame grabber and the cross-sectional areas of each tendon at each level measured using a dedicated software application. Excellent accuracy (averaging less than 5%) was demonstrated between the ultrasound generated areas and those measured from the tendons post mortem in 12 limbs. The mean, s.d. and tolerance intervals of both SDFT and DDFT cross-sectional areas at each level were determined for each group of horses. There was no statistically significant difference between Groups A and B and these 2 groups were, therefore, combined for further analysis. The cross-sectional areas of both tendons were statistically smaller for Group C when compared to Groups A and B. The ratio of SDFT to DDFT cross-sectional areas was calculated for each level and this demonstrated less variation between groups. The difference in measurements between limbs of the same horse was analysed. The mean differences for all groups were 9.13 mm2 for the SDFT and 11.64 mm2 for the DDFT. Upper limits (95% of the population) were 22.67 mm2 (SDFT) and 29.22 mm2 (DDFT).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889920 TI - Distribution of equid herpesvirus-1 (EHV-1) in the respiratory tract of ponies: implications for vaccination strategies. AB - Twelve adult ponies and 2 conventional foals were exposed to 10(6.6) TCID50 of Equid herpesvirus-1 (EHV-1), strain Ab4 and samples of respiratory tract tissues were recovered. Infectious virus in tissue homogenates was detected using susceptible cell monolayers and expression of viral antigens was monitored using indirect immunoperoxidase histochemistry of paraffin sections. The results illustrated the rapid dissemination of EHV-1 throughout the respiratory tract, with early replication in the lungs one day after exposure. Endothelial cell infection was prominent in all areas of the nasopharynx by Day 4 emphasising the role of endotheliotropism and viraemia in dissemination of this virus to sites of secondary replication. Clinical disease in the adult ponies was mild. PMID- 7889921 TI - Distribution of equid herpesvirus-1 (EHV-1) in respiratory tract associated lymphoid tissue: implications for cellular immunity. AB - Twelve adult ponies and 2 conventional foals were exposed intranasally to EHV-1, strain Ab4 (TCID50 10(-6.6) and samples of respiratory tract associated lymphoid tissues were recovered between 12 h and 13 days after infection. Infectious virus was detected in tissue homogenates using susceptible cell monolayers and expression of viral antigens was monitored using indirect immunoperoxidase histochemistry on paraffin sections. The results showed both infectious EHV-1 and viral antigens in respiratory tract associated lymph nodes 12 h after exposure. Infected leucocytes were identified morphologically as lymphocytes, monocytes, macrophages and plasma cells. The rapid intracellular localisation of EHV-1 in lymph nodes implies that cell mediated immunity is an important aspect of the equine response to this virus. PMID- 7889922 TI - Regulation of equine fibrinolysis in blood and peritoneal fluid based on a study of colic cases and induced endotoxaemia. AB - Much of the pathophysiology associated with equine gastrointestinal diseases is attributed to the effects of endotoxin on haemostasis. Because little is known about the responses of the equine fibrinolytic system to endotoxin, regulation of the system was investigated. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were identified as the primary plasminogen activator and plasminogen activator inhibitor, respectively, in equine blood. Under experimental conditions, the equine fibrinolytic system responded to endotoxin in a manner similar to that reported in man, with an early, transient increase in t-PA activity followed by an overwhelming and prolonged increase in activity of PAI-1. To investigate the response of the equine fibrinolytic system to clinical endotoxaemia, endotoxin concentrations were measured in plasma and peritoneal fluid, and activities of t-PA and PAI-1 were compared between healthy horses (n = 38) and horses with naturally occurring gastrointestinal diseases (n = 150). It was observed that plasma PAI-1 and peritoneal t-PA were increased concurrently in abnormal horses; and that these increases were associated with the presence of endotoxin. The results of this study suggest that 1) fibrinolysis is regulated in horses in a manner similar to that in man; 2) regulation of fibrinolysis is altered in endotoxaemic horses with gastrointestinal diseases; 3) events occurring in the vascular system may not reflect those in the peritoneal cavity; and 4) t-PA activity is increased in the peritoneal fluid of endotoxaemic horses with gastrointestinal diseases. PMID- 7889923 TI - A survey of exercise-induced pulmonary haemorrhage in Quebec standardbred racehorses. AB - Sixty Standardbred horses, aged 3 to 10 years, were examined endoscopically for exercise-induced pulmonary haemorrhage (EIPH) 1 h after racing, on at least 3 occasions. Racing time, finishing position and post exercise venous lactate concentrations were also recorded. Horses positive for tracheal blood on endoscopy were classified as having either grade 1 EIPH (one or a few spots of blood in the trachea), or grade 2 (stream of blood). Air temperature, relative humidity and air pollutant levels were recorded on each examination day. Of the 60 horses, 52 (87%) were EIPH-positive on at least one evaluation out of 3 and 40 of the 52 (77%) showed grade 2 EIPH on at least one occasion. Of the 52 EIPH positive horses, 52% bled 3 times out of 3, 21% 2 out of 3 and 27% once. When only the first examination was considered, 37 of the 60 horses (62%) were EIPH positive. There was no significant relation detected between either presence or frequency of EIPH and age, sex, or gait. Horses that showed grade 2 EIPH bled significantly (P = < 0.001) more frequently (mean: 83% of examinations) than horses having shown no more than grade 1 EIPH (47% of examinations). No significant differences could be detected between EIPH-positive and EIPH-negative races in the average racing times, finishing positions and blood lactate concentrations of the 29 horses which showed intermittent EIPH. The proportion of horses showing EIPH on each day where at least 5 horses were examined was correlated with air temperature, relative humidity, and the levels of several air pollutants on those days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889924 TI - Observations on the anatomy and pathology of the palmar intercarpal ligaments in the middle carpal joints of thoroughbred racehorses. AB - Ten carpi from juvenile Thoroughbred horses were dissected in detail to record the anatomy of the palmar intercarpal ligaments (PICLs). These were found not to be substantially attached to the palmar carpal ligament. The lateral PICL was sited at the convergence of the palmar aspects of the third, fourth, intermediate and ulnar carpal bones and aligned predominantly in a proximodistal direction. The medial PICL had a large origin distally on the lateral aspect of the radial carpal bone (Cr) and attached to third (C3) and second (C2) carpal bones with apparently separate fibre orientations. Fibres between Cr and C3 aligned obliquely from dorsoproximomedial to palmarodistolateral which corresponds to the direction of movement of Cr relative to C3 during carpal extension. Video recordings of arthroscopic evaluations of 67 middle carpal joints of juvenile Thoroughbred horses in race training were reviewed retrospectively and the osteochondral and ligamentous pathology visible in each recorded. Damage to the Cr-C3 part of the medial PICL was present in 47 (70%) joints and, in 6 joints, comprised complete rupture of this branch. A significant (P < 0.001) relationship was found between the presence of remodelling of the dorsodistal margin of Cr and the severity of ligament damage. It is considered that the orientation of fibres of the Cr-C3 branch of the MPICL is consistent with a putative role to alternate forces borne by Cr and C3 during axial loading of the limb and that the injuries of this structure seen in young racehorses may represent a fatigue-type pathology analogous to that seen concurrently in the related osteochondral tissues. PMID- 7889925 TI - Experimentally-induced synovitis as a model for acute synovitis in the horse. AB - The use of extremely small dosages of intra-articular E. coli lipopolysaccharide (LPS) endotoxin can create a model of synovitis that mimics acute synovitis in horses. Dosages of 5000 ng, 25 ng, 0.5 ng, 0.25 ng, 0.17 ng and 0.125 ng per joint were injected into various joints of a total of 6 horses. The dose response of LPS on clinical signs and synovial fluid parameters was evaluated at baseline and 12, 24, 36 and 48 h after LPS injection. Peripheral venous blood analysis was performed at baseline and at 0, 4, and 12 h after LPS injection. Dosages greater than 0.5 ng/joint resulted in clinical signs of endotoxaemia including fever, depression, inappetence and non-weightbearing lameness. Although the total peripheral venous leucocyte count was not decreased at any dosage, the 5000 ng/joint dosage of LPS altered venous leucocyte differential resulting in an increase in the number of segmented and band neutrophils with a concomitant decrease in lymphocytes. Synovial fluid total nucleated cell count (TNC) and total protein (TP) was linearly responsive to increases in intra-articular LPS dosages up to the 0.5 ng/joint dose. At dosages of LPS > 0.5 ng, synovial fluid mean +/- s.e.m. TNC and TP were 122.0 +/- 27 x 10(9) cells/l and 59.3 +/- 1.7 milligrams respectively, at 12 h after injection. This may represent the maximal response of the joint to increased concentrations of LPS endotoxin over 0.5 ng/joint.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889926 TI - Pulmonary vascular pressures of thoroughbreds increase rapidly and to a higher level with rapid onset of high-intensity exercise than slow onset. AB - Previous studies of pulmonary vascular pressures have utilised gradual incremental step exercise protocols, but in competitive racing at the track, horses perform rapid acceleration high-intensity exercise. The rate of rise in pulmonary vascular pressures under conditions of quick onset high-intensity exercise is unknown. Catheter mounted manometers, whose in vivo signals were matched with pressure signals obtained via transducers connected to fluid-filled lumens from same cardiovascular sites, were used to compare right heart and pulmonary vascular pressures in 8 healthy Thoroughbreds performing 2 separate exercise protocols on a high speed treadmill (gradually incremental vs. rapid acceleration exercise protocol where the belt speed was raised from 8 m/s to 15 m/s in 8 s). Heart rate, right atrial and pulmonary vascular pressures at rest were similar for the 2 protocols. Rapid acceleration of horses from 8 to 15 m/s was attended by an equally rapid escalation in the right heart and pulmonary vascular pressures such that these pressures reached their zenith as belt speed approached 15 m/s. Although exercise at 15 m/s resulted in similar heart rate in the 2 protocols, the mean +/- s.e. values of mean right atrial pressure, mean pulmonary artery pressure, mean pulmonary artery wedge pressure and mean pulmonary capillary pressure (91.5 +/- 3.9 mmHg) in the rapid acceleration exercise were significantly (P < 0.05) higher than respective values at 15 m/s in the gradual incremental step exercise protocol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889927 TI - An algorithm to describe the oxygen equilibrium curve for the thoroughbred racehorse. AB - An algorithm to describe the oxygen equilibrium curve (OEC) of the Thoroughbred horse was derived from raw oxygen equilibrium curve data obtained under standard conditions of temperature, pH and PCO2 (Smale and Butler, 1994). This algorithm was derived by a curve-fitting procedure based on the algorithm for human blood produced by Kelman (1966). The temperature, fixed acid and net CO2 coefficients were then incorporated in the algorithm to enable the accurate calculation of % saturation from any combination of PO2, temperature, pH and PCO2. The algorithm was checked using blood gas data obtained from in vivo treadmill exercise tests as well as a standardised breathing test whereby horses inhaled several different gas mixtures. This algorithm proved more accurate for the Thoroughbred horse than that derived by Kelman. PMID- 7889928 TI - Collection of venous blood samples from competition horses: a new approach. PMID- 7889929 TI - Testicular degeneration in 3 stallions. PMID- 7889930 TI - Hyperthermia during isoflurane anaesthesia in a horse with suspected hyperkalaemic periodic paralysis. PMID- 7889932 TI - Crystal structure of casein kinase-1, a phosphate-directed protein kinase. AB - The structure of a truncated variant of casein kinase-1 from Schizosaccharomyces pombe, has been determined in complex with MgATP at 2.0 A resolution. The model resembles the 'closed', ATP-bound conformations of the cyclin-dependent kinase 2 and the cAMP-dependent protein kinase, with clear differences in the structure of surface loops that impart unique features to casein kinase-1. The structure is of unphosphorylated, active conformation of casein kinase-1 and the peptide-binding site is fully accessible to substrate. PMID- 7889931 TI - The crystal structure of p13suc1, a p34cdc2-interacting cell cycle control protein. AB - p13suc1 binds to p34cdc2 kinase and is essential for cell cycle progression in eukaryotic cells. The crystal structure of S.pombe p13suc1 has been solved to 2.7 A resolution using data collected at the ESRF source, Grenoble, from both native crystals and crystals of a seleno-methionine derivative. The starting point for structure solution was the determination of the six selenium sites by direct methods. The structure is dominated by a four-stranded beta-sheet, with four further alpha-helical regions. p13suc1 crystallizes as a dimer in the asymmetric unit stabilized by the binding of two zinc ions. A third zinc site stabilizes the higher-order crystal packing. The sites are consistent with a requirement for zinc during crystal growth. A likely site for p13suc1-protein interaction is immediately evident on one face of the p13suc1 surface. This region comprises a group of conserved, exposed aromatic and hydrophobic residues below a flexible negatively charged loop. A conserved positively charged area would also present a notable surface feature in the monomer, but is buried at the dimer interface. p13suc1 is larger than its recently solved human homologue p9CKS2, with the extra polypeptide forming a helical N-terminal extension and a surface loop between alpha-helices 3 and 4. Notably, p13suc1 does not show the unusual beta-strand exchange that creates an intimate p9CKS2 dimer. p13suc1 cannot oligomerize to form a stable hexamer as has been proposed for p9CKS2. PMID- 7889933 TI - A plant basal in vitro system supporting accurate transcription of both RNA polymerase II- and III-dependent genes: supplement of green leaf component(s) drives accurate transcription of a light-responsive rbcS gene. AB - An in vitro transcription initiation system has been developed from nuclei of rapidly growing, non-green tobacco (Nicotiana tabacum) cultured (BY-2) cells. Conditions for nuclear extraction and in vitro transcription reaction have been optimized with a tobacco beta-1,3-glucanase gene, a constitutively expressed gene in BY-2 cells. The in vitro system supports accurate transcription of RNA polymerase II-dependent promoters from not only plant genes (tobacco beta-1,3 glucanase gene, cauliflower mosaic virus 35S promoter) but also animal genes (adenovirus 2 major late promoter, simian virus 40 early major promoter). In addition, this system drives accurate transcription of an RNA polymerase III dependent Arabidopsis thaliana U6 snRNA gene. As BY-2 cells do not differentiate in response to light or any other stimuli, they would provide a basal transcription system which lacks tissue-specific and light-responsive nuclear signals as well as chloroplast-derived signals. Consequently, the BY-2 cell-free system is unable to transcribe the tomato gene encoding the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (rbcS3C) whose expression is tissue-specific and light-inducible. However, the transcription of rbcS3C was obtained by supplementing the BY-2 system with a nuclear extract of light-grown tomato seedlings. The promoter regions necessary for rbcS transcription was mapped in vitro using a series of 5' deletion mutants. The 351 bp upstream sequence is essential and the further upstream region from -351 to -441 enhances its transcription. The in vitro basal system will be useful to identify specific signals from both the nucleus and chloroplast in green leaves and other organs/tissues. PMID- 7889934 TI - rpoE, the gene encoding the second heat-shock sigma factor, sigma E, in Escherichia coli. AB - In Escherichia coli, the heat shock response is under the control of two alternative sigma factors: sigma 32 and sigma E. The sigma 32-regulated response is well understood, whereas little is known about that of sigma E, except that it responds to extracytoplasmic immature outer membrane proteins. To further understand this response, we located the rpoE gene at 55.5' and analyzed the role of sigma E. sigma E is required at high temperature, and controls the transcription of at least 10 genes. Some of these might contribute to the integrity of the cell since delta rpoE cells are more sensitive to SDS plus EDTA and crystal violet. sigma E controls its own transcription from a sigma E dependent promoter, indicating that rpoE transcription plays a role in the regulation of E sigma E activity. Indeed, under steady-state conditions, the transcription from this promoter mirrors the levels of E sigma E activity in the cell. However, it is unlikely that the rapid increase in E sigma E activity following induction can be accounted for solely by increased transcription of rpoE. Based upon homology arguments, we suggest that a gene encoding a negative regulator of sigma E activity is located immediately downstream of rpoE and may function as the target of the E sigma E inducing signal. PMID- 7889935 TI - The rpoE gene encoding the sigma E (sigma 24) heat shock sigma factor of Escherichia coli. AB - Previous work has established that the transcription factor sigma E (sigma 24) is necessary for maintaining the induction of the heat shock response of Escherichia coli at high temperatures. We have identified the gene encoding sigma E using a genetic screen designed to isolate trans-acting mutations that abolish expression from either htrA or rpoHP3, two promoters recognized uniquely by sigma E containing RNA polymerase. Such a screen was achieved by transducing strains carrying a single copy of either phtrA-lacZ or rpoHP3-lacZ fusions with mutagenized bacteriophage P1 lysates and screening for Lac- mutant colonies at 22 degrees C. Lac- mutants were subsequently tested for inability to grow at 43 degrees C (Ts- phenotype). Only those Lac- Ts- mutants that were unable to accumulate heat shock proteins at 50 degrees C were retained for further characterization. In a complementary approach, those genes which when cloned on a multicopy plasmid led to higher constitutive expression of the sigma E regulon were characterized and mapped. Both approaches identified the same gene, rpoE, mapping at 55.5 min on the E.coli genetic map and encoding a polypeptide of 191 amino acid residues. The wild-type and a mutant rpoE gene products were over expressed and purified. It was found that the purified wild-type sigma E protein, when used in in vitro run-off transcription assays in combination with core RNA polymerase, was able to direct transcription from the htrA and rpoHP3 promoters, but not from known sigma 70-dependent promoters. In vivo and in vitro analyses of rpoE transcriptional regulation showed that the rpoE gene is transcribed from two major promoters, one of which is positively regulated by sigma E itself. PMID- 7889936 TI - Coordinate expression of coproporphyrinogen oxidase and cytochrome c6 in the green alga Chlamydomonas reinhardtii in response to changes in copper availability. AB - To maintain photosynthetic competence under copper-deficient conditions, the green alga Chlamydomonas reinhardtii substitutes a heme protein (cytochrome c6) for an otherwise essential copper protein, viz. plastocyanin. Here, we report that the gene encoding coproporphyrinogen oxidase, an enzyme in the heme biosynthetic pathway, is coordinately expressed with cytochrome c6 in response to changes in copper availability. We have purified coproporphyrinogen oxidase from copper-deficient C.reinhardtii cells, and have cloned a cDNA fragment which encodes it. Northern hybridization analysis confirmed that the protein is nuclear encoded and that, like cytochrome c6, its expression is regulated by copper at the level of mRNA accumulation. The copper-responsive expression of coproporphyrinogen oxidase parallels cytochrome c6 expression exactly. Specifically, the copper-sensing range and metal selectivity of the regulatory components, as well as the time course of the responses, are identical. Hence, we propose that the expression of these two proteins is controlled by the same metalloregulatory mechanism. Our findings represent a novel metalloregulatory response in which the synthesis of one redox cofactor (heme) is controlled by the availability of another (Cu). PMID- 7889937 TI - The translocation of negatively charged residues across the membrane is driven by the electrochemical potential: evidence for an electrophoresis-like membrane transfer mechanism. AB - The role of the membrane electrochemical potential in the translocation of acidic and basic residues across the membrane was investigated with the M13 procoat protein, which has a short periplasmic loop, and leader peptidase, which has an extended periplasmically located N-terminal tail. For both proteins we find that the membrane potential promotes membrane transfer only when negatively charged residues are present within the translocated domain. When these residues are substituted by uncharged amino acids, the proteins insert into the membrane independently of the potential. In contrast, when a positively charged residue is present within the N-terminal tail of leader peptidase, the potential impedes translocation of the tail domain. However, an impediment was not observed in the case of the procoat protein, where positively charged residues in the central loop are translocated even in the presence of the membrane potential. Intriguingly, several of the negatively charged procoat proteins required the SecA and SecY proteins for optimal translocation. The studies reported here provide insights into the role of the potential in membrane protein assembly and suggest that electrophoresis can play an important role in controlling membrane topology. PMID- 7889938 TI - The allele-specific synthetic lethality of prlA-prlG double mutants predicts interactive domains of SecY and SecE. AB - The secretion of proteins from the cytoplasm of Escherichia coli requires the interaction of two integral inner membrane components, SecY and SecE. We have devised a genetic approach to probe the molecular nature of the SecY-SecE interaction. Suppressor alleles of secY and secE, termed prlA and prlG, respectively, were analyzed in pair-wise combinations for synthetic phenotypes. From a total of 115 combinations, we found only seven pairs of alleles that exhibit a synthetic defect when present in combination with one another. The phenotypes observed are not the result of additive defects caused by the prl alleles, nor are they the consequence of multiple suppressors functioning within the same strain. In all cases, the synthetic defect is recessive to wild-type secY or secE provided in trans. The recessive nature argues for a defective interaction between the Prl suppressors. The extreme allele specificity and topological coincidence of the mutations represented by these seven pairs of alleles identify domains of interaction between SecY/PrlA and SecE/PrlG. PMID- 7889939 TI - Inhibition of cellular protein secretion by poliovirus proteins 2B and 3A. AB - Poliovirus RNA replication occurs on the surface of membranous vesicles that proliferate throughout the cytoplasm of the infected cell. Since at least some of these vesicles are thought to originate within the secretory pathway of the host cell, we examined the effect of poliovirus infection on protein transport through the secretory pathway. We found that transport of both plasma membrane and secretory proteins was inhibited by poliovirus infection early in the infectious cycle. Transport inhibition did not require viral RNA replication or the inhibition of host cell translation by poliovirus. The viral proteins 2B and 3A were each sufficient to inhibit transport in the absence of viral infection. The intracellular localization of a secreted protein in the presence of 3A with the endoplasmic reticulum suggested that 3A directly blocks transport from the endoplasmic reticulum to the Golgi apparatus. PMID- 7889940 TI - Mitotic HeLa cells contain a CENP-E-associated minus end-directed microtubule motor. AB - A minus end-directed microtubule motor activity from extracts of HeLa cells blocked at prometaphase/metaphase of mitosis with vinblastine has been partially purified and characterized. The motor activity was eliminated by immunodepletion of Centromere binding protein E (CENP-E). The CENP-E-associated motor activity, which was not detectable in interphase cells, moved microtubules at mean rates of 0.46 micron/s at 37 degrees C and 0.24 micron/s at 25 degrees C. The motor activity co-purified with CENP-E through several purification procedures. Motor activity was clearly not due to dynein or to kinesin. The microtubule gliding rates of the CENP-E-associated motor were different from those of dynein and kinesin. In addition, the pattern of nucleotide substrate utilization by the CENP E-associated motor and the sensitivity to inhibitors were different from those of dynein and kinesin. The CENP-E-associated motor had an apparent native molecular weight of 874,000 Da and estimated dimensions of 2 nm x 80 nm. This is the first demonstration of motor activity associated with CENP-E, strongly supporting the hypothesis that CENP-E may act as a minus end-directed microtubule motor during mitosis. PMID- 7889941 TI - Impaired interleukin-3 (IL-3) response of the A/J mouse is caused by a branch point deletion in the IL-3 receptor alpha subunit gene. AB - Interleukin-3 (IL-3) alone does not support hematopoietic colony formation of bone marrow cells from the A/J mouse. To elucidate the molecular lesion in A/J mice, we examined expression of the alpha and beta subunits of the IL-3 receptor (IL-3R). While IL-3R beta was normally expressed, IL-3R alpha was not detectable on the surface of A/J-derived cells by antibody staining. Genetic linkage analysis using recombinant inbred mouse strains between A/J and IL-3-responsive C57BL/6 indicated that the IL-3R alpha gene locus was responsible for the impaired IL-3 response in A/J mice. Molecular cloning and characterization of A/J derived IL-3R alpha cDNA revealed that it lacked the sequence corresponding to exon 8, which encodes 10 amino acid residues in the extracellular domain. The aberrant splicing was due to a 5 base pair deletion at the branch point in intron 7 and was reproduced in heterologous cells by transfecting with an IL-3R alpha minigene carrying the deleterious intron. The A/J-specific abnormal form of IL-3R alpha was localized inside the cells, but not on the cell surface, providing the molecular basis for the impaired IL-3 response in the A/J mouse. PMID- 7889942 TI - ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation. AB - Induction of the human c-fos proto-oncogene by mitogens depends on the formation of a ternary complex by p62TCF with the serum response factor (SRF) and the serum response element (SRE). We demonstrate that Elk-1, a protein closely related to p62TCF in function, is a nuclear target of two members of the MAP kinase family, ERK1 and ERK2. Phosphorylation of Elk-1 increases the yield of ternary complex in vitro. At least five residues in the C-terminal domain of Elk-1 are phosphorylated upon growth factor stimulation of NIH3T3 cells. These residues are also phosphorylated by purified ERK1 in vitro, as determined by a combination of phosphopeptide sequencing and 2-D peptide mapping. Conversion of two of these phospho-acceptor sites to alanine impairs the formation of ternary complexes by the resulting Elk-1 proteins. Removal of these serine residues also drastically diminishes activation of the c-fos promoter in epidermal growth factor-treated cells. Analogous mutations at other sites impair activation to a lesser extent without affecting ternary complex formation in vitro. Our results indicate that phosphorylation regulates ternary complex formation by Elk-1, which is a prerequisite for the manifestation of its transactivation potential at the c-fos SRE. PMID- 7889943 TI - Chromosome condensation induced by fostriecin does not require p34cdc2 kinase activity and histone H1 hyperphosphorylation, but is associated with enhanced histone H2A and H3 phosphorylation. AB - Chromosome condensation at mitosis correlates with the activation of p34cdc2 kinase, the hyperphosphorylation of histone H1 and the phosphorylation of histone H3. Chromosome condensation can also be induced by treating interphase cells with the protein phosphatase 1 and 2A inhibitors okadaic acid and fostriecin. Mouse mammary tumour FT210 cells grow normally at 32 degrees C, but at 39 degrees C they lose p34cdc2 kinase activity and arrest in G2 because of a temperature sensitive lesion in the cdc2 gene. The treatment of these G2-arrested FT210 cells with fostriecin or okadaic acid resulted in full chromosome condensation in the absence of p34cdc2 kinase activity or histone H1 hyperphosphorylation. However, phosphorylation of histones H2A and H3 was strongly stimulated, partly through inhibition of histone H2A and H3 phosphatases, and cyclins A and B were degraded. The cells were unable to complete mitosis and divide. In the presence of the protein kinase inhibitor starosporine, the addition of fostriecin did not induce histone phosphorylation and chromosome condensation. The results show that chromosome condensation can take place without either the histone H1 hyperphosphorylation or the p34cdc2 kinase activity normally associated with mitosis, although it requires a staurosporine-sensitive protein kinase activity. The results further suggest that protein phosphatases 1 and 2A may be important in regulating chromosome condensation by restricting the level of histone phosphorylation during interphase, thereby preventing premature chromosome condensation. PMID- 7889944 TI - The NIMA protein kinase is hyperphosphorylated and activated downstream of p34cdc2/cyclin B: coordination of two mitosis promoting kinases. AB - Initiation of mitosis in Aspergillus nidulans requires activation of two protein kinases, p34cdc2/cyclin B and NIMA. Forced expression of NIMA, even when p34cdc2 was inactivated, promoted chromatin condensation. NIMA may therefore directly cause mitotic chromosome condensation. However, the mitosis-promoting function of NIMA is normally under control of p34cdc2/cyclin B as the active G2 form of NIMA is hyperphosphorylated and further activated by p34cdc2/cyclin B when cells initiate mitosis. To see the p34cdc2/cyclin B dependent activation of NIMA, okadaic acid had to be added to isolation buffers to prevent dephosphorylation of NIMA during isolation. Hyperphosphorylated NIMA contained the MPM-2 epitope and, in vitro, phosphorylation of NIMA by p34cdc2/cyclin B generated the MPM-2 epitope, suggesting that NIMA is phosphorylated directly by p34cdc2/cyclin B during mitotic initiation. These two kinases, which are both essential for mitotic initiation, are therefore independently activated as protein kinases during G2. Then, to initiate mitosis, we suggest that each activates the other's mitosis-promoting functions. This ensures that cells coordinately activate p34cdc2/cyclin B and NIMA to initiate mitosis only upon completion of all interphase events. Finally, we show that NIMA is regulated through the cell cycle like cyclin B, as it accumulates during G2 and is degraded only when cells traverse mitosis. PMID- 7889945 TI - Mitotic destruction of the cell cycle regulated NIMA protein kinase of Aspergillus nidulans is required for mitotic exit. AB - NIMA is a cell cycle regulated protein kinase required, in addition to p34cdc2/cyclin B, for initiation of mitosis in Aspergillus nidulans. Like cyclin B, NIMA accumulates when cells are arrested in G2 and is degraded as cells traverse mitosis. However, it is stable in cells arrested in mitosis. NIMA, and related kinases, have an N-terminal kinase domain and a C-terminal extension. Deletion of the C-terminus does not completely inactivate NIMA kinase activity but does prevent functional complementation of a temperature sensitive mutation of nimA, showing it to be essential for function. Partial C-terminal deletion of NIMA generates a highly toxic kinase although the kinase domain alone is not toxic. Transient induction experiments demonstrate that the partially truncated NIMA is far more stable than the full length NIMA protein which likely accounts for its toxicity. Unlike full length NIMA, the truncated NIMA is not degraded during mitosis and this affects normal mitotic progression. Cells arrested in mitosis with non-degradable NIMA are able to destroy cyclin B, demonstrating that the arrest is not due to stabilization of p34cdc2/cyclin B activity. The data establish that NIMA degradation during mitosis is required for correct mitotic progression in A. nidulans. PMID- 7889946 TI - Respiratory infection with Chlamydia pneumoniae in middle-aged and older adult outpatients. AB - This study was undertaken to characterize the epidemiology and clinical presentation of infection with Chlamydia pneumoniae in a population composed primarily of middle-aged and older adults. Pharyngeal swabs and acute and convalescent phase sera were obtained from outpatients presenting with signs and symptoms of an acute respiratory infection. Sera were examined using the micro immunofluorescence (MIF) test to detect antibody to Chlamydia pneumoniae and complement fixation tests to detect Mycoplasma pneumoniae, influenza A virus, influenza B virus, respiratory syncytial virus and adenovirus. Pharyngeal swab specimens were cultured for Chlamydia pneumoniae and tested for Chlamydia pneumoniae by the polymerase chain reaction (PCR). A total of 743 patients with a mean age of 40.5 +/- 16.1 years were enrolled in the study. Twenty-one patients were serologically positive for acute Chlamydia pneumoniae infection in the MIF test. PCR was positive in 15 of the 20 serologically positive patients tested. Acute Chlamydia pneumoniae infection was identified in 3% (2/76) of subjects with pneumonia, 5% (12/247) of those with bronchitis, 5% (3/61) of those with sinusitis only and 2% (2/103) of those with pharyngitis only. Of the 21 patients with Chlamydia pneumoniae infection, seven (mean age of 33 years) had an antibody pattern suggesting a primary infection while 14 (mean age of 54 years) had a reinfection pattern. Patients with reinfection had milder disease than those with primary infection. PCR testing in the current study confirms the previously proposed serologic criteria of acute Chlamydia pneumoniae infection. PMID- 7889947 TI - Teicoplanin versus cefamandole in the prevention of infection in total hip replacement. AB - In a prospective, controlled, single-blind study the efficacy of teicoplanin versus cefamandole in preventing infections in total hip replacement was investigated in 496 consecutive patients. A single intravenous dose of teicoplanin (400 mg) was as effective as two intravenous doses of cefamandole (2 g before and 1 g after surgery). No major complications were observed in either group. Infective wound complications were observed only in the cefamandole group. These infections, although not dangerous for the patients, required supplementary antibiotic treatment in all cases. Teicoplanin is a reasonable choice as a prophylactic agent in orthopaedic surgery when a high risk of infection due to staphylococci is present. PMID- 7889948 TI - Prospective study of Candida colonization, use of empiric amphotericin B and development of invasive mycosis in neutropenic patients. AB - The association between colonization with Candida spp., subsequent occurrence of invasive candidiasis and empiric use of amphotericin B was investigated prospectively in 139 neutropenic patients with hematologic malignancies. Treatment with amphotericin B was required in 67% of patients colonized in multiple non-contiguous body sites (multicolonized) versus 31% of patients colonized in single or contiguous sites (monocolonized) and in 21% of non colonized patients (p = 0.0037 and p = 0.00026, respectively). Invasive candidiasis was documented in 22.2% of multicolonized versus 4.8% of monocolonized patients and in none of the non-colonized patients (p = 0.035 and p = 0.0036, respectively). Analysis of the spectrum of colonizing Candida spp. showed that multicolonized subjects were colonized with increased frequently by Candida albicans compared to monocolonized subjects, and that the association between multicolonization, invasive candidiasis and amphotericin B usage was statistically significant in patients colonized by Candida albicans but not in patients colonized by other Candida species. The association between Candida multicolonization and the occurrence of Candida infection seems to be confirmed by a double-blind placebo-controlled study performed in a small subgroup of the multicolonized patients treated with fluconazole. PMID- 7889949 TI - Three beta-lactamases isolated from Aeromonas salmonicida, including a carbapenemase not detectable by conventional methods. AB - The beta-lactamases of seven strains of Aeromonas salmonicida subsp. achromogenes resistant to amoxicillin (MIC > 1024 mg/l) and responsible for furunculosis in farmed Atlantic salmon in Scotland were examined to establish the mechanisms of beta-lactam resistance. Separation of a cell-free extract on an isoelectric focusing gel stained with the chromogenic cephalosporin nitrocefin showed the presence of two beta-lactamases, one with a pI of 7.9 and the other with a pI of 6.0. Hydrolysis assays of cell-free extracts of these strains demonstrated carbapenemase, penicillinase and cephalosporinase activity. However, when the beta-lactamases were separated by anion exchange chromatography, the carbapenemase activity could not be retrieved in either of the peak fractions containing the separated enzymes that had been visualised by nitrocefin. Consequently, a novel carbapenemase was discovered which cannot be detected with nitrocefin. PMID- 7889951 TI - In vitro activity of biapenem against beta-lactamase producing Enterobacteriaceae. AB - The activity of biapenem was compared with that of imipenem and cefotaxime against 108 strains of beta-lactamase producing Enterobacteriaceae. Biapenem and imipenem were very active, inhibiting 90% of the strains at a concentration of 0.5 microgram/ml. Both carbapenems were very active against plasmidic beta lactamase producers, with MIC90s below 1 microgram/ml. However, the MIC90 of biapenem for cephalosporinase producers was 1 microgram/ml. Against strains producing extended-spectrum beta-lactamases, biapenem exhibited better activity against TEM-type producers (MIC90 0.25 microgram/ml) than against SHV-type producers (MIC90 0.5 microgram/ml). Overall, the in vitro antibacterial activity of biapenem is similar to that of imipenem. PMID- 7889950 TI - Use of a receiver operating characteristic in the evaluation of two commercial enzyme immunoassays for detection of Helicobacter pylori infection. AB - Two novel commercial IgG enzyme immunoassay (EIA) systems based on acid-glycine extracted (Pyloriset IgG EIA, Orion Diagnostica) or fast protein liquid chromatography-purified (Cobas Core Anti-H. pylori EIA, Roche Diagnostic Systems) Helicobacter antigens were evaluated in a prospective study involving 127 patients. All patients underwent upper endoscopy with biopsy, and biopsies were examined for the presence of Helicobacter pylori by a rapid urease test, microscopy and culture. Of the 71 patients found to be infected with Helicobacter pylori, 69 (97.2%) and 65 (91.5%) tested positive with the Cobas Core and Pyloriset test, respectively. A detailed receiver operating characteristic analysis of the two tests showed that the Cobas Core assay was more sensitive and specific at every possible cut-off level; gave a better resolution of individual results, indicating a greater fine-sensitivity; and had no grey zone compared to a large grey zone encompassing 13.4% of the serum samples tested with the Pyloriset EIA. The Cobas Core assay appears to be a valuable tool for epidemiological purposes as well as for pre-endoscopic screening of dyspeptic patients. PMID- 7889953 TI - Reduction in human listeriosis in Barcelona, Spain. PMID- 7889952 TI - Interpretive criteria and quality control for antimicrobial susceptibility tests of levofloxacin. AB - To confirm preliminary interpretive breakpoints for prototype 5 micrograms levofloxacin disks, 490 strains were tested in vitro using commercially manufactured disks. For in vitro susceptibility testing, 5 micrograms levofloxacin disks can be used with interpretive criteria of < or = 12 mm for resistant (MIC > or = 8.0 micrograms/ml) and > or = 16 mm for susceptible (MIC < or = 2.0 micrograms/ml). Proposed quality control limits for tests of levofloxacin are as follows: Escherichia coli ATCC 25922, zones 29-37 mm or MIC 0.008-0.03 microgram/ml; Pseudomonas aeruginosa ATCC 27853, zones 19-26 mm or MIC 0.5-2.0 micrograms/ml; Staphylococcus aureus ATCC 25923, zones 24-31 mm; Staphylococcus aureus ATCC 29213, MIC 0.06-0.25 microgram/ml and Enterococcus faecalis ATCC 29212, MIC 0.25-2.0 micrograms/ml. PMID- 7889954 TI - Luxuriant growth of Helicobacter pylori and Campylobacter species in candle jars after primary isolation. PMID- 7889955 TI - Problems with identification of Acinetobacter species. PMID- 7889956 TI - Resistance to and hydrolysis of imipenem in nosocomial strains of Flavobacterium meningosepticum. PMID- 7889957 TI - Comparative microbiological activity and pharmacokinetics of cefprozil. AB - In vitro studies on the activity of cefprozil have been conducted in Europe and North America. Against gram-negative bacilli, cefprozil and cefaclor are at least two to four times more active than cephalexin. Cefixime is more active against these organisms. Against gram-positive cocci, cefprozil is at least two to four times more active than cefaclor and cephalexin; cefixime has limited gram positive activity, and is particularly inactive against staphylococci (MIC90 32 mg/l). Cefprozil is highly active against Streptococcus pneumoniae (unlike cefixime). Those strains of this genus that display intermediate resistance to pneumococci are more susceptible to cefprozil than cefaclor. Neisseria species and Moraxella catarrhalis are susceptible to cefprozil (MIC90 0.06 and 1 mg/l). beta-lactamase-producing strains of Haemophilus influenzae appear to be susceptible to cefprozil, as the reported MIC90 is 2-4 mg/l. Enterococci, Pseudomonas aeruginosa, and those strains of the Enterobacteriaceae that commonly possess a chromosomal cephalosporinase (e.g., Providencia, Morganella and Enterobacter) are generally considered to be resistant to cefprozil as well as to other oral cephalosporins. Cefprozil appears to display enhanced stability to the commonly encountered Tem-1 and SHV-1 plasmid-mediated beta-lactamases, as found in Haemophilus influenzae, Neisseria gonorrhoeae and the Enterobacteriaceae. Cefprozil is rapidly absorbed, reaching a maximum concentration 0.9 to 1.2 h post dose. Following oral doses of 250 and 500 mg, the Cmax is 6.2 and 10.0 mg/l respectively. Serum half-lives are generally reported as between 1.2 and 1.4 h, and urine recovery is high, 57-70%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889958 TI - Comparative efficacy and safety of cefprozil versus penicillin, cefaclor and erythromycin in the treatment of streptococcal pharyngitis and tonsillitis. AB - Cefprozil is a new oral cephalosporin with an enhanced in vitro spectrum of activity that includes group A beta-hemolytic streptococci (GABHS). Four multicenter randomized clinical trials were conducted to compare the clinical efficacy and safety of cefprozil administered once or twice a day for the treatment of mild to moderate GABHS tonsillitis and pharyngitis. A total of 1597 patients were enrolled in the trials. Patient demographics and severity of infection were similar for all treatment groups. In Study 1, cefprozil administered at 20 mg/kg once daily was clinically, in 68 of 76 patients (89%) and bacteriologically, in 66 of 74 patients (89%) superior to penicillin -51 of 69 (74%) and 46 of 69 (67%)--administered three times a day in patients of two to 12 years of age. In Study 2, the patients enrolled were 13 years of age and older, and cefprozil administered at 20 mg/kg once a day had similar clinical (93% vs. 90%) and bacteriological (95% vs. 94%) response rates as cefaclor administered three times a day. Study 3 demonstrated that cefprozil administered twice daily was similar to penicillin given three times a day, the clinical satisfactory response being 164 of 175 (94%) for cefprozil and 146 of 165 (88%) for penicillin. In Study 4, identical clinical and bacteriologic responses (95%) were observed for cefprozil administered once a day and erythromycin ethylsuccinate administered four times a day in children over two years of age. There were no significant differences in the incidence or severity of drug related adverse events, which, when reported, were mild and transient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889959 TI - Efficacy and safety of cefprozil versus other beta-lactam antibiotics in the treatment of lower respiratory tract infections. AB - Cefprozil was evaluated in four multicentre comparative studies in the treatment of acute respiratory tract infections. In two studies, cefprozil 500 mg q. 12 hours was compared to cefaclor 500 mg q. eight hours for ten days of therapy. Randomization was on a 2:1 (cefprozil:cefaclor) basis in the European centres and 1:1 in North America. The clinical efficacy in acute bronchitis was 88% (284 out of 324 patients) for cefprozil and 88% (183 out of 208) for cefaclor, with successful bacteriological eradication of the causative pathogen in 86% and 82% of the patients, respectively. Amongst the patients with acute exacerbations of chronic bronchitis, the clinical response rate of 80% (59 out of 74) for cefprozil appeared superior to that of cefaclor at 62% (p = 0.067), whilst the bacteriological response rates were 62% (36 out of 58) for cefprozil and 74% (20 out of 27) for cefaclor. In pneumonia, the clinical response rates for cefprozil and cefaclor therapy were similar, 82% vs. 79%, although bacteriological eradication rates were better for cefprozil at 82% than for cefaclor at 71%. In the comparison of cefprozil with cefuroxime axetil, a total of 170 patients were evaluable. The clinical and bacteriological response rates for cefprozil of 95% and 100% were better than those for cefuroxime axetil 500 mg q. 12 hours of 84% and 75%, respectively. In the cefprozil vs. amoxicillin-clavulanate, 500 mg q. eight hours comparative study, the two antibiotics displayed no significant difference in clinical or bacteriological responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889960 TI - Multi-investigator evaluation of the efficacy and safety of cefprozil, amoxicillin-clavulanate, cefixime and cefaclor in the treatment of acute otitis media. AB - Cefprozil was evaluated in the treatment of acute otitis media with effusion in three open, randomized, multicenter comparative clinical trials. In two trials, 891 pediatric patients were enrolled to either cefprozil or amoxicillin clavulanate dosage regimens. The treatment groups were comparable in demographic characteristics, and presented with otalgia, middle-ear effusion, or inflamed or bulging tympanic membrane on otoscopic examination. In all patients, tympanocentesis and a culture were required. Two cefprozil oral doses were evaluated, 30 mg/kg/day and 40 mg/kg/day divided into two equal doses (b.i.d.). Amoxicillin-clavulanate was administered at 40 mg/kg/day in three divided doses (t.i.d.). The recommended duration of therapy was ten days. The predominant bacteria isolated were Haemophilus influenzae and Moraxella catarrhalis. The overall satisfactory clinical response rates were similar for cefprozil (83%) and amoxicillin-clavulanate (81%). The bacteriological response rates did not differ significantly, at 84% and 82%. Cefprozil eradicated the most common pathogen, Streptococcus pneumoniae, more often at 91%, vs. 84% for amoxicillin-clavulanate. The eradication rates were similar against Haemophilus influenzae and Moraxella catarrhalis. The patients treated with cefprozil had a lower rate of adverse clinical events (11%) compared to those with amoxicillin-clavulanate (20%). More gastrointestinal adverse experiences, including diarrhea, were reported in the amoxicillin-clavulanate-treated patients. In Study 3, cefprozil 30 mg/kg/day (b.i.d.) was compared to cefaclor 40 mg/kg/day (t.i.d.) and cefixime 8 mg/kg/day (q.d) in the treatment of acute otitis media in 388 pediatric patients. The patients were treated for 10 days, with a follow-up of 18 days. The overall clinical cure rates were 85%, 89% and 85%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889961 TI - Comparative studies of cefprozil in the management of skin and soft-tissue infections. AB - Six multicenter clinical trials comparing cefprozil with cefaclor, amoxicillin clavulanate or erythromycin in the management of skin and soft-tissue infections caused by susceptible bacteria demonstrate that cefprozil, given once or twice daily, is an effective chemotherapeutic agent in this context. Its pharmacokinetic behavior is compatible with once-daily or twice-daily administration, with a probability of improved patient compliance. Safety and tolerability compare favorably with other agents used in skin and soft-tissue infections. PMID- 7889962 TI - Non-canonical mechanisms of antibiotic resistance. AB - Although the current in vitro methods used for detection and analysis of the phenotypes of antibiotic resistance in the laboratory are well established, other resistance mechanisms of resistance exist which may escape detection using the standard approach. The present article reviews some of these mechanisms which are grouped under the term 'non-canonical mechanisms' of antibiotic resistance. Such mechanisms include gene dosage, heterologous induction or selection, populational resistance and synergism between mechanisms of low resistance. The role of these mechanisms in the failure of therapy is discussed. PMID- 7889963 TI - Prospective study of renal transplant infections in 50 consecutive patients. AB - A prospective study of the frequency, timing, etiology and risk factors of infections in renal transplant recipients during the first year after transplantation was conducted in 50 consecutive patients. Neither prophylaxis with trimethoprim-sulfamethoxazole nor antiviral prophylaxis was administered. Two hundred twenty-eight episodes of infection were registered (4.5 per patient), 19 of which were severe. Forty-seven percent of all infectious episodes occurred during the first two months after transplantation. The more frequent infections were bacterial (64%), viral (22%) and fungal (11%). Escherichia coli was the most common agent isolated (n = 36), followed by cytomegalovirus (n = 32). Urinary tract infections were most common (n = 144), especially asymptomatic bacteriuria (n = 106). Surgical reintervention and the use of anti-lymphocytic globulins were associated with a higher frequency of severe infections (p < 0.05), and invasive candidiasis was associated with allograft loss (p < 0.03). Annual survival rates of patients and allografts were 100% and 94%, respectively. The frequency of mild infections was higher than that observed in other studies using bacterial or viral prophylaxis. Nevertheless, the number of severe infections and the survival rates of patients and allografts were similar to those reported in previous studies. PMID- 7889964 TI - Acquisition of immunity in mothers of infants administered trivalent oral poliovirus vaccine. AB - The hypothesis that live oral poliovirus vaccine (OPV) confers immunity to persons in close contact with the vaccine recipient was tested by comparing cord blood antibody titers in 31 first-born neonates to those of 48 neonates with one or more siblings adequately immunized with OPV. A borderline or negative result (defined as a reciprocal titer of < or = 8) for at least one type was significantly more prevalent among first-born neonates than among neonates with one or more siblings [17/31 (55%) versus 17/48 (27%) respectively; p < 0.03]. This difference was consistent for all three poliovirus types. The geometric mean titer (GMT) was consistently higher for each serotype in infants with one or more siblings compared with first-born neonates: 134.9 versus 64.5 for poliovirus 1; 262.1 versus 95.6 for poliovirus 2; and 48.6 versus 19.4 for poliovirus 3, respectively. When cord blood of neonates with two or more siblings was compared to that of neonates with only one sibling, no difference in titers was observed. Since mothers of one or more infants were on average older and less educated, the results were adjusted accordingly, but the same trend was observed again. These findings support the notion that OPV is important, not only as a vaccine for the individual infants, but also as a means of conferring immunity to persons in close contact. PMID- 7889965 TI - Prospective randomised comparison of single-dose versus multiple-dose cefuroxime for prophylaxis in coronary artery bypass grafting. AB - To assess the efficacy of single-dose antibiotic prophylaxis in coronary artery bypass grafting, 1,016 consecutive patients were prospectively randomized to receive either a single dose or a three-day course of cefuroxime. Nine patients (0.9%) died within seven days; no death was caused by infection. For various reasons 163 other patients were not evaluable. Therefore, 844 patients were evaluated. Patients in group A (n = 419) received 20 mg/kg cefuroxime intravenously at induction of anaesthesia; group B (n = 425) received the same dose followed by 750 mg t.i.d. for three consecutive days. Both groups were comparable regarding all risk factors. The efficacy of the prophylactic regimens was evaluated by comparison of occurrence of wound infection in both groups. No significant differences in wound infection were observed between the two treatment groups: sternal site infection in the single-dose prophylaxis group was 14% versus 13% in the three-day course group; donor site infection occurred in 38% versus 39%. It is concluded that in coronary artery bypass grafting a single dose of cefuroxime is as effective as a three-day course in the prevention of wound infection. PMID- 7889966 TI - Antibacterial activity of sucralfate versus aluminum chloride in simulated gastric fluid. AB - Studies have previously demonstrated that sucralfate possesses intrinsic antibacterial activity. This study was designed to indirectly assess whether aluminum is the active antibacterial component of sucralfate and to further evaluate factors that may influence this agent's antibacterial activity. Utilizing an in vitro model, the antibacterial activity of sucralfate, an equivalent quantity of aluminum in the form of aluminum chloride, and a control were compared. In addition, the influences of bacterial species (Enterobacter cloacae and Pseudomonas aeruginosa), time (0-24 h) and environmental pH (3,5,7) on the agents' antibacterial activities were evaluated. Equivalent quantities of aluminum, as either sucralfate or aluminum chloride, were added to two of three flasks containing approximately 10(5) cfu/ml of bacteria in pH-adjusted simulated gastric fluid. The third flask served as a control. Samples were obtained over 24 h, diluted and subcultured onto agar plates. The experiments demonstrated that bacterial growth was influenced by pH, time and treatment (aluminum chloride or sucralfate). Regardless of pH or bacterial species, bacterial death occurred within 20 min following the addition of aluminum chloride. In contrast, bacterial death following the addition of sucralfate was more variable and appeared to be pH dependent. In conclusion, sucralfate and aluminum chloride both possess antibacterial activity, even at pH values that normally support bacterial growth in gastric fluid. Although differences in the antibacterial activity of the two agents may in part be related to drug-induced changes in pH, these differences also support data suggesting that aluminum release from sucralfate is incomplete and is dependent on pH. PMID- 7889967 TI - Activity of the fourth generation cephalosporin FK-037 against methicillin resistant Staphylococcus aureus under conditions maximizing PBP2' production. AB - To investigate the in vitro activity of the fourth generation cephalosporin FK 037, MICs were determined for 80 strains of methicillin-resistant Staphylococcus aureus from 11 countries. Methicillin and cefamandole served as comparators. The method ensured good expression of PBP2' by use of a large inoculum, salt supplement and incubation for 48 hours at 30 degrees C. FK-037 was twice as active as cefamandole against both strains with high-level and strains with low level methicillin resistance (geometric mean MICs 23.4 and 10.8 mg/l, respectively). PMID- 7889968 TI - Treatment of cerebrospinal fluid shunt infections with teicoplanin. AB - Intraventricular teicoplanin 10-15 mg was administered daily to three patients with cerebrospinal fluid (CSF) shunt infections due to Staphylococcus epidermidis and Enterococcus faecalis. Teicoplanin concentrations in CSF 24 h after intrathecal injection of the drug exceeded four- to eight-fold the MICs for the infecting microorganisms. CSF cultures rapidly became negative and shunt devices were withdrawn and replaced in the same operative procedure. Intraventricular teicoplanin was well tolerated. No relapses occurred. Teicoplanin may be an alternative to vancomycin for the antimicrobial therapy of CSF shunt infections. PMID- 7889969 TI - Possible prevention of in vitro selection of resistant Streptococcus pneumoniae by beta-lactamase inhibitors. AB - The development of resistance in vitro in five strains of Streptococcus pneumoniae (3 with full susceptibility and 2 with intermediate susceptibility to penicillin) was investigated by serial passages in the presence of subinhibitory concentrations of amoxicillin and ampicillin. At the end of passaging, MICs of antibiotics for all the strains increased by a factor of four or more, reaching at least intermediate levels. MICs of cephalosporins, ampicillin and amoxicillin increased for almost all variants obtained. Similar results were obtained with amoxicillin plus clavulanic acid at a ratio of 2:1 and at a constant concentration of 2 micrograms/ml, and with ampicillin plus sulbactam at a ratio 2:1. In contrast, no significant modification of MIC was seen with ampicillin plus sulbactam at a constant concentration of 4 micrograms/ml sulbactam. These results suggest interaction of sulbactam with penicillin binding proteins as described previously for other bacterial species, and merit further investigation. PMID- 7889970 TI - Production of siderophore by coagulase-negative staphylococci and its relation to virulence. AB - The ability to produce siderophore is considered to be a virulence factor for many pathogenic bacteria. To determine if siderophore production by coagulase negative staphylococci (CNS) was related to virulence, 40 clinical isolates of CNS cultured from peritoneal dialysis fluid were compared with 38 commensal skin isolates. Siderophore activity was detected using the chrome azurol S liquid assay. Using precursor studies, Staphylococcus epidermidis isolates were shown to be more likely to produce the siderophore staphyloferrin A. Production of staphyloferrin B amongst non-Staphylococcus epidermidis species was associated with clinical isolates rather than commensal isolates, and therefore may play a role in pathogenicity. PMID- 7889971 TI - Mycoplasma genitalium in the joints of two patients with arthritis. AB - Mycoplasma genitalium was sought in synovial fluids from 13 patients, of whom five had Reiter's syndrome, four had rheumatoid arthritis, and one each had systemic lupus erythematosus, psoriatic arthritis, rheumatic fever and undefined arthritis. The mycoplasma was detected by a PCR assay in the knee joint of a 25 year-old man with Reiter's syndrome, from whom urethral ureaplasmas were isolated and whose synovial fluid mononuclear cells responded to ureaplasmal antigens in a proliferation assay. Mycoplasma genitalium was also detected in the knee joint during an exacerbation of arthritis in a 58-year-old man who had had seronegative juvenile polyarthritis that had evolved to seronegative rheumatoid arthritis. PMID- 7889972 TI - A fatal case of systemic strongyloidiasis and review of the literature. AB - Systemic strongyloidiasis is a rare but serious complication of intestinal strongyloidiasis. The condition occurs mainly in immunosuppressed patients and has a significant mortality rate. A case of systemic strongyloidiasis is described in a patient who received systemic steroid treatment, and a short review of the literature is given. The increased use of immunosuppressive and cytotoxic treatment necessitates increased awareness of this infection. HIV infection, however, does not appear to increase the risk of developing systemic strongyloidiasis. Patients from endemic areas and travellers to such areas, even in the remote past, should be examined for strongyloidiasis before being given immunosuppressive treatment. Awareness of the possibility of systemic strongyloidiasis is essential if such a patient develops gastrointestinal or pulmonary symptoms or has repeated episodes of unexplained gram-negative infections while undergoing immunosuppressive treatment. PMID- 7889973 TI - Isolation of Vero cytotoxin-producing Escherichia coli serotypes O9ab:H- and O101:H-carrying VT2 variant gene sequences from a patient with haemolytic uraemic syndrome. AB - Vero cytotoxin-producing Escherichia coli (VTEC) were isolated from the faecal specimen of a patient with haemolytic uraemic syndrome. The isolates belonged to two rare VTEC serotypes, O9ab:H- and O101:H-. Polymerase chain reaction gene amplification products were detected with primers specific for the VT2e gene, a variant of VT2. The toxin from both isolates was cytotoxic to Vero cells but not to HeLa cells. An 18 kb EcoRI restriction enzyme fragment of genomic DNA from both strains hybridised with a VT2 polynucleotide DNA probe. PMID- 7889974 TI - Distribution of coagulase-negative staphylococci, including the newly described species Staphylococcus schleiferi, in nosocomial and community acquired urinary tract infections. AB - Four hundred and four coagulase-negative staphylococci were isolated from 4905 urine specimens obtained from 4192 inpatients and outpatients. The distribution of the strains was as follows: 193 Staphylococcus epidermidis (47.8%), 171 Staphylococcus saprophyticus (42.3%), 29 Staphylococcus haemolyticus (7.2%), 5 Staphylococcus warneri (1.2%), 3 Staphylococcus schleiferi (0.7%), 2 Staphylococcus hominis (0.5%) and 1 Staphylococcus simulans (0.2%). All three Staphylococcus schleiferi strains were isolated from inpatients: a 64-year-old female, a 68-year-old male and a 3-month-old male with colony counts of 468,000 cfu/ml, 324,000 cfu/ml and 764,000 cfu/ml respectively. These findings show that among coagulase-negative staphylococci, Staphylococcus schleiferi, a newly described species of coagulase-negative staphylococci not previously reported as a uropathogen, may also cause hospital acquired urinary tract infection. PMID- 7889975 TI - Comparison of polymerase chain reaction with standard methods in the diagnosis of Mycobacterium tuberculosis infection. AB - The polymerase chain reaction (PCR) method was evaluated in the detection of Mycobacterium tuberculosis in comparison with direct microscopy and culture procedures including the standard radiometric system (Bactec). Amplified DNA fragments from clinical samples were analyzed by dot-blot and non-radioactive oligonucleotide hybridization techniques or by agarose gel electrophoresis. The results revealed nested PCR to be the method of choice. The combination of three culture methods could detect Mycobacterium tuberculosis in only 79% of PCR positive cases. The mean time required to achieve a positive culture result was 17 days in contrast to the PCR method requiring only two to three days. The nested PCR assay provided rapid and reliable results allowing a definitive diagnosis particularly in a number of samples which were negative on culture. PMID- 7889976 TI - Granulomatous infection due to Propionibacterium acnes mimicking malignant disease. PMID- 7889977 TI - Suspected transmission of eczema herpeticum in a thermal bath establishment. PMID- 7889978 TI - Potential inhibition of alkylating agent metabolism by fluconazole. PMID- 7889979 TI - Revision of quality control limits for broth microdilution tests of fleroxacin and gentamicin with Pseudomonas aeruginosa ATCC 27853. PMID- 7889980 TI - Isoproterenol-induced redistribution of endosomes in cardiac myocytes. AB - During myocardial infarction, it is well known that the cytoplasm of cardiac myocytes becomes more acidic due to lactate accumulation. The resulting necrosis is believed to result, at least in part, from the leakage of lysosomal enzymes into the cytoplasm. In addition, it has previously been shown that cytoplasm acidification in tissue culture cells can cause the redistribution of late endosomes and tubular lysosomes. In the present study, we have investigated whether lysosomal/endosomal structures were affected during isoproterenol-induced infarct-like myocardial necrosis in rat heart in vivo. In parallel, we treated rat primary myocyte cultures with a high dose of isoproterenol or low pH. We followed the fate of lysosomal enzymes, a lysosomal membrane glycoprotein and the cation-independent mannose 6-phosphate receptor. Lysosomes were intact until irreversible injury became evident suggesting that the lysosomal enzyme release concomitant with the leakage of cytoplasmic enzymes is merely a consequence of cell death. During the early phase of injury, when the myocyte cytoplasm was mildly acidified, late endosomes showed fragmentation and microtubule-dependent movement towards the periphery, while the subcellular distribution of lysosomes was unchanged. Both processes were also observed after mild artificial acidification of the cytoplasm. Our data show that late endosomes and lysosomal trafficking are affected early during isoproterenol-induced myocardial injury causing a pH-dependent redistribution of late endosomes. PMID- 7889981 TI - Expression of activated RAF accelerates cell differentiation and RB protein down regulation but not hypophosphorylation. AB - Expression of an activated raf transgene accelerated the terminal myeloid differentiation of HL-60 human promyelocytic leukemia cells induced by retinoic acid. A similar result was obtained when 1,25-dihydroxyvitamin D3 was used to induce monocytic differentiation. The stable transfectants were derived by transfecting HL-60 cells with DNA encoding an N-terminal truncated raf-1 protein. In normal HL-60 cells retinoic acid is known to induce a colony-stimulating factor-1 (CSF-1)-dependent metabolic cascade culminating in G0 arrest and phenotypic conversion. Early in this cascade, expression of the RB tumor suppressor gene product is down-regulated. A progressive redistribution of the form of the protein from largely hyperphosphorylated protein to the hypophosphorylated form begins later with G0 arrest and differentiation. In the activated raf-transfected cells, RB down regulation occurred more rapidly, consistent with accelerated differentiation. But the conversion to the hypophosphorylated form was not accelerated and occurred after G0 arrest and phenotypic conversion to myeloid differentiated cells. Thus raf activation appears to be a component of the induced metabolic cascade culminating in terminal differentiation. In this cascade raf activation promotes RB down regulation. The data are consistent with a model in which raf is an effector of the CSF-1-dependent metabolic cascade which culminates in terminal cell differentiation, and RB downregulation is one of the downstream consequences of RAF action. Furthermore, they indicate that RB down-regulation may be an essential component of the cellular processes causing G0 arrest and differentiation, but RB hypophosphorylation is more likely a consequence thereof and not a cause. PMID- 7889982 TI - Tumorigenic transformation of established murine fibroblasts by transfection with amplification promoting DNA elements. AB - Deregulated replication of the cellular genome is assumed to result in tumorigenic transformation of the cell. We tested this hypothesis by using mouse DNA elements that promote amplification of transfected DNA in mammalian cells when linked to a selectable marker gene that is driven by a truncated promoter (Holst et al., Cell 52, 355-365 (1988); Wegner et al., Nucl. Acids Res. 17, 9909 9932 (1989)). Here, the DNA elements muNTS-1, e-1, e-2, e-4, e-5, and e-12 were inserted into the plasmid p-hyg, which contains the gene for resistance to hygromycin B driven by a constitutive promoter. After transfer into established rat fibroblasts (208F), transfected DNA constructs persist in low copy numbers (1 10 copies per cell) integrated into high molecular weight DNA. We observed a neoplastically transformed phenotype in 40% to 70% of hygromycin-resistant colonies of 208F cells which is dependent on the DNA element transfected. 208F cells transfected with vector DNA exhibit a "normal" phenotype and are not tumorigenic. The transformed cells, on the other hand, induced malignant tumors after injection into immunodeficient NMRI nu/nu mice. In contrast to established cells, primary rat embryo fibroblasts (REF) with limited life span are neither neoplastically transformed nor immortalized after transfection of e-4 DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889983 TI - Expression of a 46 kDa protein in human pancreatic tumors and its possible relationship with the bile salt-dependent lipase. AB - Bile salt-dependent lipase (BSDL), an enzyme normally found in human pancreatic secretions is a 100 kDa glycoprotein. A BSDL-specific 477 bp cDNA probe was prepared by performing polymerase chain reaction experiments. This cDNA was used to probe mRNAs extracted from human pancreatic tissue and tumoral cell lines. Two mRNAs were detected in normal human pancreas at 2.2 and 1.3 to 1.5 kb. In human pancreatic tumoral cells, mRNAs encoding for the BSDL were detected using in situ hybridization, and proteins with an M(r) of 46,000 to 48,000 were translated into an in vitro system using mRNAs extracted from these cells. Using an immunoprecipitation procedure, we observed here that the specific BSDL polyclonal antibodies recognized three proteins of 100 +/- 5 (p100), 46 +/- 2 (p46) and 22.7 +/- 1.2 (p23) kDa, respectively in the soluble extracts of normal adult human pancreas. The p100 protein was probably the glycosylated product resulting from the translation of the 2.2 kb transcript. The p46 protein, which electrophoresed as a doublet was the main component immunoprecipitated from extract of a differentiated human pancreatic adenocarcinoma as well as from the extracts of two pancreatic cell lines, BxPC-3 and SOJ-6. In addition, the p46 immunoform of the BSDL was detected in cell-free medium from SOJ-6 cell line and its expression was found to be correlated with the secretion of an esterolytic activity on 4 nitrophenyl caproate, whereas the BxPC-3 cell line neither secreted the p46 nor showed any esterolytic activity on this substrate. The p46 may be either a short variant of BSDL resulting from the translation of the 1.3 to 1.5 kb transcript or a protein structurally related to the enzyme. The p46 doublet immunoform was detected in the human pancreatic secretion. PMID- 7889984 TI - 3-Methyladenine inhibits transport from late endosomes to lysosomes in cultured rat and mouse fibroblasts. AB - The effect of 3-methyladenine on transport from endosomes to lysosomes was studied in rat embryonic and mouse 3T3 fibroblasts. Subcellular fractionation in 27% Percoll gradients showed that the pre-endocytosed (5 min pulse) horseradish peroxidase (HRP) was not transported from endosomes to dense lysosomes in cells chased in the presence of 10 mM 3-methyladenine. However, fractionation in 20% Percoll gradients, which separated early endosomes from late endosomes and lysosomes, as well as light and electron microscopic experiments, showed that HRP was transported from early endosomes to the perinuclear late endosomes. Immunoprecipitation of metabolically labeled cells was used to study the biosynthetic processing of a lysosomal proteinase, cathepsin L. The results showed that the early processing of the precursor to the intermediate form was not affected by 3-methyladenine, while the late processing of the intermediate to the mature form was retarded. In addition, immunofluorescence labeling showed that 3-methyladenine treatment caused accumulation of cathepsin L in the perinuclear area. Another lysosomal enzyme, beta-glucuronidase, was normally distributed in both perinuclear and peripheral vesicles which indicated that the localization of lysosomes was not altered. The results thus suggest that the late processing of cathepsin L was inhibited because transport from perinuclear endosomes to lysosomes was retarded. In conclusion, both endocytic pulse-chase experiments and immunoprecipitation of metabolically labeled cathepsin L indicate that 3-methyladenine inhibits transport from late endosomes to mature lysosomes in both rat and mouse fibroblasts. PMID- 7889985 TI - Phenotype-associated lectin-binding profiles of normal and transformed blood cells: a comparative analysis of mannose- and galactose-binding lectins from plants and human serum/placenta. AB - Surface glycoconjugates of normal and transformed blood cells are commonly characterized by plant lectins. To infer physiological significance of protein carbohydrate interactions, mammalian lectins are obviously preferable as research tools. So far, human serum lectins have not been used to assess their binding to immunophenotyped human normal or transformed blood cells. Thus, our study combines two groups of lectins with different specificity from plant and human sources. Besides concanavalin A (ConA) we have isolated the mannose-binding protein and serum amyloid P component from human serum. Especially the mannose binding protein is believed to play a role in host defence against bacteria and yeast cells with unknown impact on normal and tumor cells. These three lectins establish the first group. In addition to the immunomodulatory mistletoe lectin, whose binding can elicit enhanced cytokine secretion from mononuclear blood cells, we included the beta-galactoside-binding lectin (14 kDa) from human placenta in the second group. The initial series of measurements was undertaken using two-color flow cytometry to determine the phenotype-associated binding (based on cluster designation; CD) of the lectins to blood and bone marrow cells from normal donors and the cell line CEM (T-lymphoblastoid), KG1-A (primitive myeloid leukemia) and Croco II (B-lymphoblastoid). Heterogeneity was apparent for each lectin in the CD-defined cell populations. Significant differences in binding were noted between Viscum album agglutinin (VAA) and other lectins for CD4+ cells from blood and between mannose-binding protein (MBP) and VAA versus 14 kDa, ConA and serum amyloid P component (SAP) for CD19+ cells from bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7889986 TI - Differential expression of the gap junction proteins connexin45, -43, -40, -31, and -26 in mouse skin. AB - The expression of five different members of the gap junction multigene family, connexin (Cx)45, -43, -40, -31, and -26 was investigated in embryonic and adult mouse skin. For this purpose, polyclonal antibodies to Cx31 and Cx45 were raised by immunizing rabbits with fusion proteins of glutathione S-transferase and carboxy-terminal peptides including 65 amino acids of Cx31 or 138 c-terminal amino acids of Cx45, respectively. Here we describe characterization of the affinity-purified Cx31 antibodies in human HeLa cells, transfected with mouse Cx31 coding DNA, and in mouse keratinocyte-derived cell lines. In the epidermis of embryonic mice at day 19 of gestation Cx43 and -45 were detected in the basal layer, while the stratum spinosum showed expression of Cx43, -31 and -26. In the stratum granulosum we found expression of Cx31 and -26. In the epidermis of adult mice Cx43 and -31 were located similarly as in embryonic tissue, but Cx45 as well as Cx26 were not detected and in addition Cx40 was weakly expressed in the stratum basale. Furthermore, during hair development, Cx31 was detected in the inner epithelial root sheath and sebaceous glands of hair follicle. Cx43 and -40 were found in the outer epithelial root sheath and to a lesser extent in sebaceous glands. Cx31 was also demonstrated in Hel-37 and Hel-30, i.e. two related cell lines derived from mouse keratinocytes. Our results show that epidermal and follicular differentiation coincides with differential expression of five different connexin proteins, suggesting specific and coordinated function(s) of gap junctional communication during skin and hair development. PMID- 7889987 TI - Immunolocalization of the lactotransferrin receptor on the human T lymphoblastic cell line Jurkat. AB - Monoclonal antibodies have been raised against the soluble lactotransferrin binding protein purified from the cell culture supernatant of Jurkat cell line, a human T-lymphoblastic cell. All monoclonal antibodies were able to specifically bind to the membrane of Jurkat cells. One of the monoclonal antibodies, DP5B3G10, recognized both the soluble lactotransferrin-binding protein and the membrane lymphocyte lactotransferrin receptor after SDS-PAGE in presence of 2 mercaptoethanol and electrotransfer on nitrocellulose. The monoclonal antibody DP5B3G10 inhibited the binding of lactotransferrin to Jurkat cells and human peripheral activated lymphocytes. In addition, lactotransferrin inhibited the binding of the monoclonal antibody to the cell surface. These results suggest that the 95 kDa lactotransferrin-binding protein isolated from the cell culture medium corresponds to the soluble form of the 105 kDa lymphocyte lactotransferrin receptor. Corresponding proteins of 105 kDa molecular mass were identified in Jurkat and CEM T-cells and Raji B-cells. Finally, the monoclonal antibody DP5B3G10 was used to immunolocalize the lactotransferrin receptor on the Jurkat cells. Using fluorescence and electron microscopy, the receptor was localized both inside and at the cell surface. The cell membrane receptor was associated into clusters. After permeabilization of the plasma membrane, the staining was positive in the peri-membrane area. The region near the nucleus was devoid of receptor. PMID- 7889988 TI - Fluorescence excimer formation imaging: a new technique to investigate association to cells and membrane behavior of glycolipids. AB - A new fluorescence ratio imaging technique aiming to monitor the lateral distribution of pyrene-labeled lipids in the membranes through visualization of the excimer/monomer (E/M) intensity ratio, has been set up, studying the association of a fluorescent derivative of GM1 ganglioside (pyreneGM1) to rat cerebellar granule cells in culture. The imaging results show that the mean E/M ratio value, under experimental conditions leading to the association of pyreneGM1 with the plasma membrane, is significantly higher in neuritic processes than in cell bodies and, moreover, locally distributed in patches. Fluorescence antisotropy imaging of the fluorescent probe TMA-DPH (trimethylaminodiphenylhexatriene) shows the presence of domains having different fluidity and that the average fluidity is higher in cell bodies than in neuritic processes. Additional experiments using TMA-DPH as a marker of fluid-phase pinocytosis, suggest that the rate of endocytosis is comparable in the two regions of the cell. Taken together, on the one hand these data indicate that the fluorescent ganglioside is present in a more clustered state at the level of neuritic processes than in cell bodies and locally distributed in patches of different size and enrichment. On the other hand, they point out the potentiality of the excimer formation imaging technique to study membrane behavior and dynamics of pyrene-labeled lipids, with a particular insight into their aggregative properties. PMID- 7889990 TI - Intracellular calcium alterations and free radical formation evaluated by flow cytometry in endotoxin-treated rat liver Kupffer and endothelial cells. AB - During endotoxic shock, the liver exerts an endotoxin (lipopolysaccharide, LPS) clearance function with the participation of both sinusoidal (mainly Kupffer and endothelial cells) and parenchymal cells. In order to determine the specificity and diversity of response of each liver cell type, the effect of Escherichia coli 0111:B4 endotoxin (LPS) on intracellular Ca2+ content and reactive oxygen metabolite production in rat liver Kupffer, endothelial and parenchymal cells, was evaluated by flow cytometry during short treatment times (from 0-2 min) with a low dose of LPS (10 micrograms/ml). Concerning sinusoidal cells, LPS produced a significant increase of intracellular Ca2+ in both endothelial and Kupffer cells. The LPS effect on Kupffer cells was higher than on endothelial cells. When intracellular reactive oxygen metabolite production was evaluated in LPS-treated sinusoidal cells, a fast and significant increase of Kupffer cells in activated state (cells with a high reactive oxygen intermediate production) was observed. However, endothelial cells did not show LPS-induced changes in their intracellular reactive oxygen metabolite content. All these results support a rapid activation of liver Kupffer cells by endotoxin consistent with the major role of this cellular type as active first line of defense during endotoxic shock. The liver endothelial cells are also involved in the first steps of the cell damage showing intracellular Ca2+ alterations. Liver parenchymal cells did not show any response at these experimental conditions (short treatment time and low LPS dose) indicating that longer treatment times are needed for LPS binding and action in agreement with previous studies. PMID- 7889989 TI - The down-side of platelet interaction with surfaces. AB - Events occurring on the exposed luminal surface of blood platelets during interaction with foreign surfaces have been evaluated in detail, but the down side has received less attention. The present study has examined the interaction of platelets with glass precoated with fibrinogen-gold (Fgn/Au), latex spherules, or cationized ferritin (CF) and compared their organization on the ventral surface with the fate of the same particulates when added to platelets already spread on glass or formvar grids. Platelets spread readily on the particle-coated glass surface. During early stages of interaction, particles of Fgn/Au, CF and latex were taken up by channels of the open canalicular system (OCS). Fgn/Au and CF often reached the dorsal surface through OCS channels where they were moved to platelet centers. In contrast, layers of Fgn/Au, CF and latex remained evenly dispersed from edge to edge on the down-side of spread platelets. Clearance of particulates from peripheral and intermediate to central zones under spread platelets was not observed. Particulates did not move from the up-side around platelet margins to the down-side, or from the ventral surface around edges to the up-side, unless spread cells were in contact. Thus, particulates use the OCS as a two-way street. The persistence of evenly dispersed layers of Fgn/Au, CF or latex on precoated glass under spread or spreading platelets indicates a significant difference in the way particulates are handled on the free upside and bound down-side. The results support the concept that the main purpose of mobile receptors is to facilitate spreading, and that the down-side is a protected zone of adhesion. PMID- 7889991 TI - Immunocytochemical detection of the specific association of different PIC isoforms with cytoskeletal and nuclear matrix compartments in PC12 cells. AB - The increasing evidence of discrete roles of phosphoinositidase C (PIC) isoforms and the assessment of their localization in the cytoskeleton and in the nucleus support the involvement of particular isotypes of this enzyme in signal transduction at multiple levels. PC12 rat pheochromocytoma is one of the few cell lines expressing three immunologically distinct isoforms of PIC. We have analyzed the subcellular distribution of the PIC beta 1, gamma 1 and delta 1 isoforms using confocal and electron microscope immunocytochemistry. PIC beta 1 is mainly found in the nucleus and is associated with interchromatin domains. On the other hand, the PIC gamma 1 isoform is found in the nucleus and in the cytosol, while PIC delta 1 is exclusively cytoplasmic. Immunoblot and immunocytochemical experiments indicate that the various PIC isoforms are differently bound to structural cell compartments, such as cytoskeletal and nuclear matrix elements. In fact, PIC beta 1 and PIC gamma 1 isoforms are tightly associated with the nuclear matrix, while only about 50% of PIC gamma 1 is associated with the cytoskeleton after DNase I and high salt extractions. PIC gamma 1 is almost completely soluble under these conditions. These results further confirm the complexity of the inositide signal transduction mechanism, which involves several PIC isoforms, specifically localized in different cell compartments and support the existence of a membrane-unrelated inositol lipid-dependent signalling in the nuclear interior. PMID- 7889992 TI - Immunocytochemical localization of heterologously expressed adrenodoxin and its electron acceptor cytochrome P45011B1 in Escherichia coli. AB - Adrenal steroid hydroxylase P45011B1 and its electron donor adrenodoxin were localized in the cortex of bovine adrenals by immunogold-silver staining. In order to test recently developed heterologous expression systems for both enzymes to enable structure-function studies, immunocytochemical marker methods were applied. Adrenodoxin, the ferredoxin of the adrenal gland, was successfully expressed and for the first time localized in Escherichia coli. By use of ultrathin cryosections and the protein A-gold technique, adrenodoxin was detectable in large amounts in the cytoplasm of the bacterial cells, and, following the insertion of the outer membrane protein A leader sequence of E. coli, also in the periplasmic space. A fusion protein between mature adrenodoxin and human P45011B1 was constructed and clearly localized in E. coli by antibodies against both proteins. PMID- 7889993 TI - Detection of G-protein heterotrimers on large dense core and small synaptic vesicles of neuroendocrine and neuronal cells. AB - Heterotrimeric G proteins, initially believed to be exclusively present in the plasma membrane, have also been found to be associated with intracellular membrane compartments. There they are involved in various membrane trafficking processes including regulated secretion (reviewed in Bomsel, M., K. Mostov, Mol. Biol. Cell 3, 1317-1328 (1992)). Vesicles of two distinct types enter the regulated secretory pathway, i.e. large dense core vesicles and small synaptic vesicles, which differ in their membrane composition and content. Little is known about an association of heterotrimeric G proteins with regulated secretory vesicles, that would explain some aspects of the role heterotrimeric G proteins have during secretion. By immunofluorescence microscopy and immunoreplica analysis, we provide the first demonstration of the presence of complete sets of heterotrimeric G proteins, consisting of alpha-, beta-, and gamma-subunits, on large dense core vesicles from bovine adrenal medulla (chromaffin granules) and small synaptic vesicles from rodent and bovine brain. Each of the two types of secretory vesicles contains beta-subunits (at least beta 1 and beta 2), as well as gamma-subunits (at least gamma 2 or gamma 3). Interestingly, they differ in their composition of alpha-subunits. On small synaptic vesicles, we found two G(o) alpha-subunits (alpha o1 and alpha o2) and two Gi alpha-subunits (alpha i1 and alpha i2). In contrast, on chromaffin granules so far only one alpha o subunit but no alpha i-subunits could be detected. Functional properties such as transmitter storage and/or exocytotic membrane fusion may be modulated by the various G-protein subunits associated with chromaffin granules and small synaptic vesicles. PMID- 7889994 TI - Ultrastructure and molecular composition of the central filament body in hydrozoan cnidocils. AB - The cnidocils of hydrozoan nematocytes contain modified microtubular axonemes and a cross-striated central filament body. Filament body and axonemal microtubules are interconnected by cross-bridges or are directly attached to one another. Structure and molecular composition of the central filament body was analyzed by means of electron microscopy and immunological techniques. The spindle-like, cross-striated filament body is composed of less than 4 nm thick subfibers. Each unit of its periodical striation pattern is approximately 19 nm broad and comprises subzones with different electron densities. Pure filament bodies are obtainable by a lysis of isolated cnidocils in detergent- and EDTA-containing buffers. The filament body is soluble in 5 mM dithioerythritol (DTE) or 1 M urea. Its structure is stabilized by high concentrations of Na+ or K+ (0.5 M both). Intermediate states of assembly can be induced by 1 mM DTE in lysis buffer which causes the filament bodies to spread into subfibers. CFB43, a monoclonal antibody against filament body protein reacts with a 33 kDa protein in Hydra. Like a polyclonal antibody against SF-assemblin, the protein forming cross-striated system I fibers in unicellular green algae, the antibody cross-reacts with a 36 kDa protein obtained from the unicellular organism Tetrahymena. In immunogold labeling experiments, CFB43 binds to the central filament body in Hydra and recognizes an epitope on the striated rootlets associated with the basal bodies of Tetrahymena. Our results indicate that the central filament body of hydrozoan cnidocils is composed of a protein with properties similar to those of SF assemblin. In combination with microtubules, the filament body seems to participate in the formation of a stiff mechanical backbone within the cnidocils. PMID- 7889995 TI - Hormonally induced changes in apocrine secretion of transglutaminase in the rat dorsal prostate and coagulating gland. AB - Coagulating gland and dorsal prostate of the rat are peculiar in secreting transglutaminase, a protein-cross linking enzyme that is released in an apocrine fashion. To elucidate whether or not the intracellular pathway and the unusual extrusion mechanism proceed constitutively or were differentially regulated, transglutaminase immunoreactivity was studied both at the light and electron microscopic levels. In addition, ultrastructural morphometry and scanning densitometry were applied to quantitate hormone-dependent distribution of transglutaminase. Coagulating glands and dorsal prostate, respectively, from sexually active rats were compared to those from sexually inactive, castrated, estradiol-treated or testosterone-substituted castrated animals. In intact, sexually active animals, no labeling of the cisternae of rough endoplasmic reticulum was seen, but instead the hyaloplasm was labeled. In the supranuclear portions of the cells an increase in labeling density of the hyaloplasm subjacent to the plasma membrane was found, whereas no labeling of either Golgi stacks or vesicles was observed. Apical blebs projecting into the acinar lumen were densely labeled. In castrated animals, epithelium showed a reduction of rough endoplasmic reticulum, loss of secretory blebs, and a decrease in cell size. Morphometric analysis of immunolabeling of coagulating gland epithelium from experimental animals resulted in a highly significant reduction of labeling of the hyaloplasm and apical blebs which was reversed by testosterone supplementation of castrated animals. After estrogen treatment, the reduction in immunolabeling was less pronounced, but morphology of apical blebs was obviously changed. Results from scanning densitometry of Western blots correlated with quantitative immunoelectron microscopical findings. Northern blot analysis using a secretory transglutaminase cDNA probe showed characteristic changes at the RNA levels. Our results indicate that apocrine secretion of transglutaminase in rat coagulating gland and dorsal prostate is a hormonally controlled process, where androgen deprivation results in impaired biosynthesis and release of transglutaminase, whereas estradiol treatment only partially inhibits secretion, but changes morphological features of the glandular epithelium, especially apocrine bleb formation. PMID- 7889996 TI - Compartmentalization of certain components of the protein synthesis apparatus in mammalian cells. AB - A comparative study on the localization of free cytosolic tryptophanyl-tRNA synthetase (TrpRS) and several components of the multi-aminoacyl-tRNA synthetase (ARS) complex (glutamyl-prolyl-tRNA synthetase (GluProRS), arginyl-tRNA synthetase (ArgRS)), and two non-synthetase polypeptides p38 and p43 has been carried out on ultrathin sections of cultured rabbit kidney cells by the immunogold technique using monoclonal antibodies raised against appropriate polypeptides. It has been shown that GluProRS, ArgRS and p38 polypeptide are distributed in the cells similarly to TrpRS and are located mainly in the vicinity of ribosomes. A smaller but significant portion of these proteins has been observed in the nuclei in the diffuse chromatin regions and in the vicinity of interchromatin granules. On the contrary, the main part of p43 protein was found in the cell nuclei; this indicates that this protein may exist in the cell separately from the cytoplasmic multi-ARS complex. Our results argue in favor of compartmentalization of both free ARS (such as TrpRS) and the multi-ARS complex in the vicinity of ribosomes. At the same time, the detection of some ARS in the diffuse chromatin regions in the nucleus implies that these enzymes may exhibit some non-canonical functions in addition to their role in protein synthesis. PMID- 7889997 TI - Properties of fluorescently labeled Xenopus lamin A in vivo. AB - Wild type Xenopus lamin A, a lamin A mutant lacking the carboxy-terminal cysteine (C662-->S), and human vimentin were expressed in bacteria and fluorescently labeled with 5-iodoacetamidofluorescein (5-IAF). In vitro reconstitution experiments and microinjection of both lamins into living cells revealed that they were indistinguishable from the non-fluorescently labeled proteins. When the 5-IAF lamin A was microinjected into the cytoplasm of 3T3 cells it was rapidly transported into the nucleus, giving rise within 1 h to a strong lamina fluorescence, whereas the lamin A mutant formed dotlike intranuclear aggregates. 5-IAF lamin A associated with the nuclear envelope of microinjected 3T3 cells and 5-IAF vimentin which was incorporated into the preexisting vimentin filaments of this cell line, were analyzed by photobleaching employing two different methods, (i) scanning microphotolysis using a modified laser scanning microscope, and (ii) the conventional photobleaching technique in which the integral fluorescence of a single spot was measured by photon counting. A low but significant fluorescence recovery was measured within 10 min for both 5-IAF-labeled intermediate filament proteins, lamin A and vimentin, in bleached areas of the nuclear envelope and the cytoplasmic intermediate filaments, respectively. PMID- 7889998 TI - Cytochemical and immunocytochemical characterization of nuclear bodies during hibernation. AB - Brown adipose tissue and liver of hibernating, arousing and euthermic individuals of the dormouse Muscardinus avellanarius were studies using ultrastructural cytochemistry and immunocytochemistry with the aim to investigate possible fine structural modifications of the cell nucleus during the seasonal cycle. The general morphology of brown adipocyte and hepatocyte nuclei was similar in the three experimental groups. However, three nuclear structural constituents were identified only in hibernating individuals: coiled bodies (CBs) and amorphous bodies (ABs) were observed in hepatocytes and, together with bundles of nucleoplasmic fibrils (NF), were present in brown adipocytes of hibernating dormice. In arousing animals only some structural constituents suggestive of poorly structured CBs were found. The latter showed the same immunocytochemical features as CBs of hibernating individuals, suggesting that they are disappearing CBs. A possible involvement of CBs in storing and/or processing RNA which must be rapidly and abundantly released upon arousal is discussed. ABs similarly to CBs contain RNA and nucleoplasmic ribonucleoproteins (RNPs) and could also be involved in mRNA pathways. NF do not contain nucleic acids or RNPs and seem to be composed of protein-aceous material; their functional role in the nuclear metabolism of hibernating brown adipocytes remains unclear. PMID- 7889999 TI - A non-cycling mitotic cyclin in the naturally synchronous cell cycle of Physarum polycephalum. AB - A universal model of the control of the cell cycle in eukaryotic organisms has emerged from the discovery that MPF (maturation or mitosis promoting factor) is a heterodimer consisting of a catalytic subunit (p34cdc2) and a regulatory subunit (mitotic cyclin) encoded by a pair of conserved genes. A prominent feature of the periodic activation of the protein kinase p34cdc2 is the gradual accumulation of cyclin in interphase and its abrupt degradation in mitosis, which is believed to be required for inactivation of MPF and exit from mitosis. Utilizing the precise natural synchrony of mitosis of the plasmodium of the myxomycete Physarum, the high affinity of the p34cdc2/cyclin B complex to p13suc1 Sepharose beads, and immunological reagents including three different anticyclin B antibodies and the anti-PSTAIR antibody, a transient histone H1 kinase activation but not fluctuation in the abundance of cyclin B have been detected during mitosis. It is argued that cyclin degradation may be required for cytokinesis and/or postmitotic controls of cell proliferation in G1 phase and cell-to-cell signaling in development but not for the inactivation of histone H1 kinase in mitosis. PMID- 7890000 TI - Endotoxemia and intestinal mucosal dysfunction after the relief of obstructive jaundice by internal and external drainage in rats. AB - We studied the effects of external and internal biliary drainage on the development of endotoxemia in a rat model of obstructive jaundice. Male Donryu rats were allocated to four groups: sham operation, common hepatic bile duct ligation (BDL), internal or external biliary drainage after BDL, and biliary drainage after BDL with oral endotoxin administration. Portal and systemic blood endotoxin concentrations were measured and the histomorphology of the intestinal mucosa was examined. Portal endotoxemia was observed 7 days after BDL and both portal and systemic endotoxemia were observed after 14 days. Portal endotoxemia was reversed by both internal and external biliary drainage and systemic endotoxemia was prevented. The ratio of villous height to crypt depth in the mucosa of the terminal ileum was decreased in rats with external drainage. Oral administration of endotoxin induced marked disruption of the mucosal epithelium in rats with external biliary drainage, but not in rats with internal biliary drainage. Significant increases in portal and systemic blood endotoxin concentrations were observed only in the external drainage group after oral endotoxin administration. The relief of biliary obstruction effectively relieved portal endotoxemia. External biliary drainage, however, has the potentially deleterious effect of disrupting the intestinal mucosa, which may promote the development of endotoxemia. These findings have implications for the use of biliary drainage procedures to reduce postoperative complications in jaundiced patients. PMID- 7890001 TI - Syngeneic small-bowel grafting increases susceptibility to lethal graft-versus host disease in the rat. AB - The rat model has been used to present evidence of the effect of surgical damage on the immune system. Syngeneic small bowel transplantation (SBT) has been used to show an increased incidence of graft-versus-host disease (GVHD) as well as thymic atrophy and altered host T cell proliferative response. Syngeneic auxiliary SBT was carried out between (LEW x BN)F1 hybrids. Varying amounts of LEW mesenteric lymphocytes were injected into the last animals to induce GVHD. Results showed that in the SBT recipients the incidence of lethal GVHD was increased when compared with untreated or sham-laparotomy controls. Marked thymic atrophy was also observed, while the number of hepatic lymphocytes increased transiently. Lymphocyte proliferation in response to concanavalin A or interleukin-2 was impaired for up to 21 days postoperatively, whereas the mixed lymphocyte reaction reactivity was not affected. These results show that the number and proliferative activity of thymic T cells were impaired after major small bowel transplantation surgery and that extrathymic lymphocytes were developed in the liver. PMID- 7890002 TI - Histopathologic studies of gastric mucosa following gastric substitution in benign and malignant esophageal disease. AB - Gastric interposition was performed and prospectively studied in 9 patients with esophageal cancer, 1 patient with esophageal neurofibroma and 5 with corrosive esophageal stricture. The postoperative follow-up periods were between 6 to 68 months with a mean of 28.6 months. The subjects were then endoscopically reviewed. Twelve of them were macroscopically normal. The others exhibited signs of inflammation and hyperemia. Mucosal biopsies were obtained at the upper and lower third of the graft. The histologic findings were compared with those of the preoperative specimens. Among the 15 post-operative specimens, only minute histologic changes were seen. Three patients whose proximal grafts showed inflammatory signs revealed congestion. Another 2 patients exhibited granulocyte infiltration in the mucosa of the distal third. The mucosal structure of the remaining 10 patients was similar to that of the preoperative graft. In conclusion, the macroscopic and microscopic changes were few and minimal although there were alterations in function, physiology and location of the stomach. PMID- 7890003 TI - Increased gastric acid secretion after massive small bowel resection is related to a decrease in enterogastrones. AB - The reported increase of gastric secretion after small bowel (SB) resection is controversial. To determine the effect of SB resection on gastric acid secretion we studied basal and dose step pentagastrin-stimulated gastric acid secretion as well as basal serum gastrin, secretin, neurotensin and postprandial gastrin levels in 12 dogs, before and after resection of 60% of the intestine representing both proximal (n = 6) and distal (n = 6) SB. Rat bioassay was also performed to rule out the presence of unknown gastric secretagogues in the blood. Proximal SB resection produced a significant increase in basal and low dose (100 ng/kg/h) pentagastrin-stimulated gastric acid secretion (ED50 = 1,110 vs. 720 ng/kg/h after resection). However, no significant changes in gastric secretion were observed after distal SB resections. Neither proximal nor distal SB resection altered basal or postprandial serum gastrin levels. Proximal SB resection reduced serum secretin levels (229 +/- 38 vs. 134 +/- 16 pg/ml, p < 0.05) but did not alter neurotensin levels. Rat bioassay failed to reveal a circulating secretagogue after SB resections. We conclude that proximal but not distal SB resection increases basal and submaximally stimulated gastric acid secretion. Such an effect may be due to the observed decrease in circulating secretin levels. PMID- 7890004 TI - Ascorbate preserves gastric mucosal metabolism and microcirculation after hemorrhagic shock and retransfusion in rats. AB - The gastric mucosal microcirculation and purine nucleotide metabolism were studied in rats after hemorrhagic shock and retransfusion. The mucosal surface density of perfused vessels (SDPV) and the mucosal levels of ATP, ADP, AMP, IMP, hypoxanthine and uric acid were measured following 15 min of hemorrhagic shock and 10 and 30 min after retransfusion, and the effects of pretreatment with allopurinol or ascorbate were studied. During shock there was a dephosphorylation of nucleotides and a decline in the SDPV. Retransfusion led to an additional reduction in the SDPV, but a complete restoration of preshock nucleotide levels 30 min after retransfusion. Allopurinol accelerated early rephosphorylation of nucleotides without effects upon SDPV while ascorbate completely preserved the mucosal level of energy-rich nucleotides 15 min after hemorrhagic shock and increased SDPV during early reperfusion. The results showed that there was a renewal of energy stores in gastric mucosa after hemorrhagic shock and retransfusion although parts of the vascular bed were not reperfused. The mucosal energy depletion after 15 min of hemorrhagic shock and part of the mucosal vessel injury after retransfusion were prevented by pretreatment with ascorbate. PMID- 7890006 TI - Effect of gabexate mesilate on thrombin and plasmin generation after hepatic resection in cirrhotic patients. AB - The effect of the gabexate mesilate (Gab) on thrombin and plasmin generation following liver resection in cirrhotic patients was studied. Six cirrhotic patients received an infusion of Gab after liver resection (Gab group), and another 6 patients did not receive such treatment (Con group). The parameters measured were thrombin-antithrombin complex (TAT), plasmin-antiplasmin complex (PAP) and D-dimer. The real increases of D-dimer and PAP were significantly higher in Con group after surgery while no significant difference was observed in the increase of TAT. These results show that Gab suppresses plasmin generation and following D-dimer production more effectively than thrombin generation after hepatic resection. PMID- 7890005 TI - Effectiveness of Carolina rinse solution after cold ischemic storage of rat livers: biochemical and histological analysis using perfusion model. AB - Using a rat liver perfusion model, the effectiveness of Carolina rinse solution was assessed for the prevention of reperfusion injury after 48 h of cold storage in UW solution. Transaminase levels (GOT, GPT and LDH) of the perfusate were significantly higher in the Ringer group (17 +/- 8, 17 +/- 9 and 191 +/- 97 IU/l, respectively) than in the Carolina group (6 +/- 4, 5 +/- 4 and 21 +/- 20 IU/l) (p < 0.05). The levels of oxygen consumption were also higher in the Carolina group (233 +/- 54 mm Hg) than in the Ringer group (164 +/- 58 mm Hg) (p < 0.05). Histological examination showed severe parenchymal cell damage in the Ringer group, whereas the damage was slight in the Carolina group. Two newly developed monoclonal antibodies, REC16-11 and REC4-1, which specifically react with rat endothelial cells, were used for immunohistochemical studies of the livers. The endothelial cells of central vein and sinusoids were more severely damaged in the Ringer group than in the Carolina group. The present study suggests that Carolina rinse solution is useful for prevention of liver damage from reperfusion injury after cold storage of the graft for organ transplantation. PMID- 7890007 TI - Sacral root stimulation for controlled defecation. AB - Selective rectal or sphincter neurostimulation aiming at controlled defecation was performed in 10 dogs. While the dogs were under anesthesia, the rectal and rectal neck pressures, balloon expulsion as well as external anal sphincter (EAS) response to stimulation of the second sacral ventral nerve root (S2) and its autonomic and somatic branches were determined. Each of these nerves was stimulated separately using bipolar platinum cuff electrodes. S2 stimulation resulted in rectal and rectal neck pressure elevation as well as increase of EMG activity of EAS without balloon expulsion. Autonomic branch stimulation effected rectal pressure increase and balloon expulsion, while somatic branch stimulation caused increase of rectal neck pressure and EAS EMG activity with no balloon expulsion. S2 stimulation with somatic branch transection produced rectal pressure elevation and balloon expulsion. In contrast to rectal pressure, the rectal neck pressure increased with increasing stimulus frequency. In conclusion, rectal evacuation and sphincteric control could be induced by selective sacral root electrostimulation: S2 stimulation with transection of the somatic branch for the former and pudendal branch stimulation for the latter. PMID- 7890008 TI - Apoptosis in disease. PMID- 7890009 TI - The HELP-LDL-apheresis multicentre study, an angiographically assessed trial on the role of LDL-apheresis in the secondary prevention of coronary heart disease. II. Final evaluation of the effect of regular treatment on LDL-cholesterol plasma concentrations and the course of coronary heart disease. The HELP-Study Group. Heparin-induced extra-corporeal LDL-precipitation. AB - The efficacy of the heparin-induced extracorporeal LDL-precipitation (HELP) apheresis procedure has been studied in an open prospective multicentre trial. After 2 years of regular weekly HELP-treatment the data from 39 of 51 patients could be evaluated according to the study criteria. Twelve of the initially recruited study patients were omitted from the evaluation either because of premature termination of the treatment or because they did not fulfil the exact guidelines of the study protocol. A mean of 2.831 plasma was regularly treated on average every 7.85 days. The mean pre-/post-apheresis LDL-cholesterol levels decreased from 286/121 mg dl-1 at the first HELP treatment to 203/77 mg dl-1 after 1 year and to 205/77 mg dl-1 after 2 years of regular apheresis; the corresponding values for fibrinogen were 314/144, 246/98 and 250/105 mg dl-1, respectively. In contrast, the mean pre-/post-apheresis HDL-cholesterol levels rose from 41/38 through 51/44 mg dl-1 after 1 year to 52/43 mg dl-1 after 2 years of treatment. The overall result was a normalization of the atherogenic index (LDL-/HDL-cholesterol ratio) from 6.9/3.2 to 4.0/1.9. The angiographies from 33 patients obtained before and after 2 years of regular treatment could be evaluated blindly using the cardiovascular angiography analysis system. The mean degree of stenosis of all segments decreased from 32.5% (SD = 16) to 30.6% (SD = 16.8) over the 2 years. A regression > 8% was observed in 50/187 (26.7%) segments, whereas 29/187 (15.5%) segments showed progression. In 108/187 (57.8%) segments the lesions were stable (< 8% deviation) over 2 years. We conclude that regular treatment with HELP-LDL-apheresis is able to stabilize progressive atherosclerotic disease and to induce almost twice as much regression as progression of atherosclerotic lesions. PMID- 7890010 TI - Hormone replacement therapy may reduce high serum homocysteine in postmenopausal women. AB - In a prospective study we investigated the possible changes in fasting serum total homocysteine concentrations during continuous micronized 17 beta oestradiol, 2 mg daily, in combination with cyclic dydrogesterone, 10 mg daily during the first 14 days of each 28 day cycle, in 21 healthy non-hysterectomized postmenopausal women. During the first six cycles mean serum homocysteine decreased by 10.9% (P = 0.013), after which no further significant changes were found during the 2 years of treatment. A 16.9% decrease (P = 0.017; n = 8) was found in women with high homocysteine concentrations, while in women with low homocysteine concentrations (n = 13) no significant changes were observed. The observed decrease in high homocysteine concentrations in postmenopausal women may in part contribute to the decreased risk of developing cardiovascular disease during hormone replacement therapy. PMID- 7890011 TI - Platelet transmembrane signalling responses to collagen in familial hypercholesterolaemia. AB - Washed platelets from patients with familial hypercholesterolaemia (FH) were found to be more reactive towards collagen than those from control subjects. The dose required to achieve half maximum aggregation was found to be 0.6 ml-1 for FH patients whilst that for control subjects was 1.25 micrograms ml-1. In both types of platelet, intracellular Ca2+ levels, as monitored by the Ca(2+)-dependent photoprotein, aequorin, rose on stimulation with collagen and then fell to basal levels, probably due to resequestration by the reticular system. This effect was not due to exhaustion of the supply of aequorin since sustained Ca2+ influx induced by the ionophore, A23187, gave a stable signal that did not return to baseline. Similarly, inositol 1,4,5, trisphosphate levels increased in the cytosol after stimulation and then fell to unstimulated values. When stimulated with collagen, platelets from FH patients showed a greater extent of cytoplasmic calcium mobilization (P < 0.05) when compared to controls, coupled with a greater extent of inositol phospholipid hydrolysis (P < 0.05). At doses of collagen sufficient to give either 100% or 50% aggregation, platelets from patients or control subjects showed the same amplitude of ATP release at either dose suggesting that the trigger for vesicle release is more sensitive in FH. PMID- 7890012 TI - Effects of bile salt and phospholipid hydrophobicity on lithogenicity of human gallbladder bile. AB - Increased biliary bile salt and phospholipid hydrophobicity may promote nucleation of cholesterol crystals and gallstone formation. We therefore compared bile salt composition (determined by gas-liquid chromatography) in patients with cholesterol (n = 35) and pigment (n = 16) gallstones (group A). Bile salt composition and cumulative bile salt hydrophobicity index were not different between both stone types. Hydrophobicity index or % of individual bile salts did not correlate with cholesterol saturation index or nucleation time. In an additional 21 cholesterol stone patients (group B) biliary bile salt and phospholipid hydrophobicity as determined by high-pressure liquid chromatography did not correlate with cholesterol saturation index or nucleation time. In both group A and group B, cholesterol stone patients with cholesterol crystals in their fresh biles had a higher % deoxycholic acid, a lower % cholic acid and a higher bile salt hydrophobicity index than crystal-negative patients. This study indicates the need for further research on the role of bile salt hydrophobicity in the pathogenesis of gallstones. PMID- 7890013 TI - Persistence of counter-regulatory abnormalities in insulin-dependent diabetes mellitus after pancreas transplantation. AB - Conventional insulin therapy does not correct the counter-regulatory abnormalities of insulin-dependent diabetes mellitus. Pancreas transplantation is an alternative therapy that restores the endogenous insulin secretion in diabetes. In this study, the effects of segmental pancreas transplantation on counter-regulation to mild hypoglycaemia were evaluated. Glucose kinetics and the counter-regulatory hormonal responses were assessed in eight insulin-dependent diabetics with end-stage renal failure who had received pancreas and kidney transplantation 1 year previously, seven diabetic uraemic subjects (candidates for combined transplantation), five patients with chronic uveitis on immunosuppressive therapy comparable to pancreas recipients and 10 normal subjects. Insulin (0.3 mU kg-1 min-1) was infused for 2 h to induce mild hypoglycaemia (plasma glucose 3.2-3.5 mmol l-1) and exogenous glucose was infused as required to prevent any glucose decrease below 3.1 mmol l-1. After transplantation, two of eight recipients had hypoglycaemic episodes reported in their medical records. During the study, hepatic glucose production was rapidly suppressed in the controls and in the patients on immunosuppression (-80 +/- 7 and -54 +/- 7%, P < 0.001 vs. basal), and rebounded to the baseline values within 1 h (-3 +/- 1 and -6 +/- 2%, P = NS vs. basal). The transplant recipients had similar suppression in the first hour (-88 +/- 8%, P < 0.001 vs. basal), but the suppression persisted in the second hour (-69 +/- 11%, P < 0.001 vs. basal) indicating a lack of glucose counter-regulatory response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7890014 TI - The effect of probucol and vitamin E treatment on the oxidation of low-density lipoprotein and forearm vascular responses in humans. AB - This study investigates the hypothesis that lipid soluble antioxidants may increase the resistance of low-density lipoprotein (LDL) to oxidation and also enhance vascular endothelial responses in humans. In a double-blind parallel group study, 24 hypercholesterolaemic patients already on treatment with simvastatin (20 mg day-1), were randomized to supplementary treatment with probucol (500 mg bd), vitamin E (400 IU daily) or placebo for 8 weeks. Mean serum cholesterol before antioxidant treatment was 7.00 mmol l-1. Resistance of LDL to oxidation by copper was increased by 830% in the probucol group and by 30% in the vitamin E group. However, thiobarbituric acid reacting substances in whole serum were not altered by either antioxidant. Probucol lowered HDL- and LDL-cholesterol levels and increased the QT interval. Forearm vascular responses, as measured by venous occlusion plethysmography, to acetylcholine, glyceryl trinitrate and NG monomethyl-L-arginine, were not significantly changed by antioxidant treatment. Probucol has a major, and vitamin E a minor, effect on LDL resistance to oxidation but neither compound appears to alter forearm vascular responses in vivo. PMID- 7890016 TI - Systemic interleukin-1 alpha and interleukin-2 secretion in response to acute stress and to corticotropin-releasing hormone in humans. AB - Acute stress results in activation of the hypothalamic-pituitary-adrenal (HPA) axis. ACTH and cortisol secretion is stimulated by corticotropin-releasing hormone (CRH). It has also been shown that activation of the HPA axis during stress is accompanied by changes in the immune response. However, little is known about the influence of acute stress on the release of cytokines such as interleukin-1 (IL-1) or interleukin-2 (IL-2). In this study, we determined serum IL-1 alpha and IL-2 levels in 19 patients undergoing the acute stress of angioplasty for coronary artery disease. A second protocol was devised to determine serum IL-1 alpha and IL-2 concentrations as well as lymphocyte subpopulations in 10 normal volunteers receiving 1 microgram kg-1 human CRH intravenously. Finally, IL-1 alpha concentrations were measured in CRH-incubated mononuclear cell (MNC) and monocyte cultures. In response to the stress of angioplasty, ACTH and cortisol as well as IL-1 alpha and IL-2 concentrations were clearly above baseline levels (IL-1 alpha, mean +/- SEM, baseline: 1.39 +/- 0.34 ng ml-1, after angioplasty: 2.64 +/- 0.73 ng ml-1, P < 0.05; IL-2, baseline: 1.2 +/- 0.13 ng ml-1, after angioplasty: 2.8 +/- 1.14 ng ml, P < 0.05). A similar pattern was obtained in normal subjects in response to CRH (Il-1 alpha, baseline: 0.8 +/- 0.2 ng ml-1, after angioplasty: 3.7 +/- 1.4 ng ml-1, P < 0.05; IL-2, baseline: 1.9 +/- 0.4 ng ml-1, after angioplasty: 5.4 +/- 2.2 ng ml-1, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7890015 TI - Inhibition of human vascular smooth muscle cell proliferation by lovastatin: the role of isoprenoid intermediates of cholesterol synthesis. AB - Restenosis remains the largest single obstacle to the long-term success of invasive vascular interventions. Lovastatin, an HMG-CoA reductase inhibitor, has been shown to reduce myointimal hyperplasia in animal models of restenosis and in one clinical coronary restenosis trial. We have assessed the effect of lovastatin on the growth of cultured human vascular smooth muscle cells derived from saphenous vein and vascular graft stenoses. Lovastatin (2 microM) inhibited proliferation over 14 days in saphenous vein (and graft stenoses) derived vascular smooth muscle cells by 42% and 32% respectively: this was not significantly different. Lovastatin (10 microM) reduced [methyl 3H]-thymidine uptake by 51% in saphenous vein-derived cells. These concentrations were significantly higher than those achieved in plasma during therapeutic dosage. Lovastatin-induced inhibition of vascular smooth muscle cell proliferation and [methyl 3H]-thymidine uptake was completely reversed by adding mevalonate (100 microM) but cholesterol (10-40 micrograms ml-1) had no effect. Isopentenyl adenine (25-50 microM) did not affect the inhibition of [methyl 3H]-thymidine uptake by lovastatin (10 microM), but farnesol (20 microM), another isoprenoid precursor of cholesterol synthesis, reversed the antiproliferative effect. PMID- 7890017 TI - Influence of weight reduction on platelet volume: different effects of a hypocaloric diet and a very low calorie diet. AB - Since platelet volume reflects platelet activity, the mean platelet volume (MPV) is proposed to be a further independent risk factor for cardiovascular disease (CVD). Even if it is well established that weight reduction reduces some of the risk factors of CVD in obese patients, an increase of MPV occurs during periods of weight loss. We therefore prospectively investigated the effects of different weight reduction therapies on platelet mass, platelet volume, body weight and serum lipid profile in patients undergoing an 8 week weight reduction therapy either by a hypocaloric diet (HD) or a nutritionally completed very low calorie diet (VLCD) with a subsequent maintenance period of 40 weeks. In both groups, MPV transiently increased during the 8 week diet period. After 48 weeks the MPV was decreased to initial values. The change in MPV was significantly (P < 0.05) smaller in the VLCD group. We therefore suggest that fasting might alter the control of platelet size with a possible impact on platelet activity. This might result in an increased risk for thromboembolic ischaemic events in atherosclerotic patients. Thus, we conclude that the use of a VLCD is potentially superior for weight reduction in patients with pre-existing atherosclerosis. PMID- 7890018 TI - Transgenic animals in male reproduction research. AB - Although transgenic mouse technology has already been widely used for the study of gene function and regulation in many areas of biomedicine, it has been applied only sporadically to the investigation of testicular function. Nevertheless, the contribution of this experimental approach to the understanding of male reproduction is considerable, not least because of the frequency of infertility in transgenic mice. Transgenic mice can be produced by microinjection of DNA constructs in the male pronucleus of fertilized eggs that are then retransferred into the oviducts of pseudopregnant females and allowed to develop to term. A proportion of the offspring have the foreign DNA sequences permamently integrated into the genome and thus become transgenic. In this way it is possible to obtain either the over-expression of genes, which can be targeted to the testis using testis-specific promoters, or to effect interruption of the functional integrity of genes by insertional mutagenesis. The regulation of gene expression in vivo can be studied by producing transgenic mice where the transgene is composed of the regulatory sequences of a gene of interest driving the expression of a reporter gene. Specific genes can be "knocked out" by homologous recombination. This article reviews the contribution of the transgenic approach to the following areas of male reproduction: the identification of factors involved in sex determination and development of the reproductive tract; the study of the function and expression of genes important for spermatogenesis and male reproduction; the identification of genes involved in spermatogenesis and of genomic sequences directing the expression of a transgene in the testis; the study of the function of specific reproductive tissues or cells in vivo; oncogenesis in reproductive tissues; the creation of cell lines suitable for in vitro studies; gene therapy. PMID- 7890019 TI - Structure-function relationship of glucose transporters catalyzing facilitated diffusion. PMID- 7890020 TI - Secretory pattern of metabolic hormones in the lactating sow. AB - Two experiments were conducted to monitor hormonal changes during lactation in crossbred sows (Pietrain x German Landrace). Sows were fed twice daily without weighing the remaining food. Number of piglets was not standardized. Plasma concentrations of growth hormone (GH), prolactin (PRL), insulin-like growth factor-1 (IGF-1), IGF-2, insulin (INS), triiodothyronine (T3), thyroxin (T4), free thyroxin (FT4), non esterified fatty acids (NEFA) and glucose (GLUC) were determined by RIA, EIA or enzymatically. In exp. A (n = 5 sows), blood samples were taken via permanent jugular cannula in weekly 24 h windows at 20 min intervals and additionally once daily for 6 weeks during lactation and for 3 days after weaning. In exp. B (n = 24 sows), blood was collected by needle puncture of the ear vein 2 and 1 week before parturition, the 1st and 3rd-4th week of lactation and 1 and 2 weeks after weaning. GH (0.8 ng/ml) and PRL (10.2 ng/ml) increased with onset of lactation (3.3 resp. 91.5 ng/ml), remained at high levels (2.5-2.8 resp. 39-41 ng/ml) during the 2nd and 3rd week, declined slowly thereafter and considerably after weaning to concentrations of 0.7 resp. 2.7 ng/ml. During lactation in 4 of 5 sows in exp. A, the typical episodic secretory pattern of GH and PRL was lost due to frequent suckling. Basal values, as known from non lactating sows, were not reached and number of pulses was elevated during lactation for both pituitary hormones. Insulin levels showed a high individual variation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7890021 TI - In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of Agnus castus: direct evidence for a dopaminergic principle by the dopamine receptor assay. AB - Women suffering from premenstrual mastodynia often respond to stimuli of prolactin (Prl) release with a hypersecretion of this hormone. Pharmacological reduction of Prl release by dopamine agonists or treatment with extracts of Agnus castus (AC) improve the clinical situation of patients with such premenstrual symptoms. Extracts of AC contain compounds which inhibit in vivo Prl release in women as well as in vitro from dispersed rat pituitary cells. It is yet unknown whether this inhibitory action of AC is only exerted on Prl release or whether release of other pituitary hormones like LH and FSH is also affected. The effects of AC on LH and FSH release were examined in vitro using rat pituitary cell cultures. To rule out that the Prl-inhibiting properties of AC are at least in part due to a cytotoxic component, pituitary cell cultures were subjected to the MTT test. To assess whether the Prl inhibitory effect of AC preparations is due to compounds acting as dopamine (DA) agonists, we used the corpus striatum membrane DA receptor binding assay. Our results demonstrate for the first time that AC extract contains an active principle that binds to the D2 receptor. Thus, it is very likely that it is this dopaminergic principle which inhibits Prl release in vitro from rat pituitary cells. Furthermore we give evidence for the specificity of action of AC on hormone release, since gonadotropin secretion remained unaffected. The findings of the present study support the therapeutical usefulness of AC extracts for treatment of premenstrual mastodynia which is associated with hypersecretion of Prl. Furthermore, the beneficial effects of AC appear to be due to the inhibition of pituitary Prl release. PMID- 7890022 TI - Immunohistochemical studies on specificity and affinity of the BB5-antibody against human parathyroid tissue. AB - Localisation of parathyroid tissue in hyperparathyroidism may be difficult with standard methods. Immunoscintigraphy, using radiolabeled antibodies against epitopes of human parathyroid cells, could be a promising alternative. Therefore, we studied the necessary preconditions, whether the so-called BB5-antibody, directed against parathyroid cell membranes possesses sufficient specificity and affinity to be employed in immunoscintigraphy. Specificity was tested immunohistochemically with APAAP-staining of 39 different human tissues. Additionally, an immunoscore-based quantitative comparison was performed to test the affinity of BB5-antibody for normal and pathologic parathyroid tissue. Specificity was proven by the fact that of all 39 tested tissue-types only the parathyroid tissue was BB5-positive. Normal parathyroid tissue showed a significantly higher affinity to the BB5-antibody than pathologic parathyroid tissue (p < 0.03). However, all tissue samples from primary or secondary hyperparathyroidism exhibited sufficient staining. We conclude that the BB5 antibody fulfills the necessary conditions to be tried for immunoscintigraphical localisation of the parathyroid glands. PMID- 7890023 TI - Cholinergic potentiation of the meal-related rise in ACTH and cortisol concentrations in men. AB - The present study examined the influence of physostigmine, an acetylcholine esterase inhibitor, on the secretory activity of the hypothalamo-pituitary adrenocortical (HPA)--axis under basal (experiment I) and stimulated (experiment II) conditions in young healthy men. In a third experiment, the effect of scopolamine, a muscarinic acetylcholine receptor antagonist, on HPA secretory activity after physiological stimulation was tested. The experiments started between 09.00 and 10.00 a.m.. After a resting period of 1.5 h, either physostigmine (0.0125 mg per kg body weight soluted in isotonic saline) or placebo (saline) was infused within 15 min. In experiment I subjects (n = 7) remained fasting while in experiment II (n = 18) a standardized lunch was offered after the infusion. Experiment III (n = 7) was designed as experiment II but instead of physostigmine, scopolamine or placebo (0.5 mg) was subcutaneously injected 105 min before the meal. Blood for the determination of ACTH and cortisol was drawn in regular intervals during the experiments. Physostigmine did not change basal ACTH and cortisol secretion per se, excluding activation of basal HPA secretion due to acetylcholineesterase inhibition and its non specific side effects. Meal intake stimulated ACTH and cortisol secretion which was significantly enhanced when physostigmine was administered (p < 0.05). Scopolamine did not influence the meal related ACTH and cortisol secretion. These findings demonstrate that cholinergic neurotransmission is able to increase ACTH and cortisol concentrations in humans. This effect seems to be complementary to other stimulatory neurotransmitter systems, and is functional during stimulated HPA secretory activity and not under basal conditions. PMID- 7890024 TI - Structure and mechanism of inositol monophosphatase. AB - Since lithium inhibits IMPase and modulates phosphatidylinositol (PtdIns) cell signalling at therapeutically relevant concentrations (0.5-1.0 mM), IMPase has attracted attention as a putative molecular target for lithium in the treatment of manic depression. IMPase is a homodimer, with each subunit organised in an alpha beta alpha beta alpha arrangement of alpha-helices and beta-sheets, and this type of structure seems crucial to the two-metal catalysed mechanism in which an activated water molecule serves as a nucleophile. Lithium appears to inhibit the enzyme following substrate hydrolysis by occupying the second metal binding site before the phosphate group can dissociate from its interaction with the site 1 metal. The understanding of IMPase structure and the mechanism of substrate hydrolysis and lithium inhibition should be useful in the development of novel inhibitors which may prove clinically useful in the treatment of manic depression. PMID- 7890025 TI - Interaction of a synaptobrevin (VAMP)-syntaxin complex with presynaptic calcium channels. AB - Nerve terminal protein complexes implicated in exocytosis were examined by immuno isolation from rat brain synaptosomes. Immunoprecipitation with anti-syntaxin or anti-VAMP antibodies revealed a syntaxin-SNAP25-VAMP-synaptotagmin complex. Anti VAMP antibodies also trapped a distinct VAMP-synaptophysin complex. A similar fraction (about 70%) of N-type calcium channels ([125I]omega conotoxin GVIA receptors), was immunoprecipitated by either anti-syntaxin or anti-VAMP antibodies, but not by anti-synaptophysin antibodies (< 4%). The majority of N- but not L-type calcium channels ([3H]PN200-110 receptors), appear to be associated with a synaptic vesicle prefusion complex. PMID- 7890026 TI - A subtype of opioid kappa-receptor is coupled to inhibition of Gi1-mediated phospholipase C activity in the guinea pig cerebellum. AB - PLC activity was stimulated either by 1-100 microM of GTP or by 100-3,000 microM Ca2+ in lysed synaptosomal membranes of the guinea pig cerebellum. The kappa opioid receptor agonist selectively inhibited the PLC activity stimulated by 100 microM GTP, but not by 100-3,000 microM Ca2+. Pretreatment of membranes with PTX abolished such a kappa-agonist-induced inhibition of PLC activity. The reconstitution of Gi1, but not of Go purified from porcine brains with PTX treated membranes showed a complete recovery of the kappa-agonist-inhibition of PLC activity. These findings suggest that a novel subtype kappa-receptor mediates inhibition of PLC through inhibiting the intrinsic activity of PTX-substrate G proteins. PMID- 7890027 TI - Site-directed mutagenesis of histidine residues in the delta 12 acyl-lipid desaturase of Synechocystis. AB - In the cyanobacterium Synechocystis sp. PCC 6803, there are four acyl-lipid desaturases that are, respectively, specific to the delta 6, delta 9, delta 12 and omega 3 positions of fatty acids. The desA gene for the delta 12 acyl-lipid desaturase was modified by site-directed mutagenesis, such that four of the histidine residues that are conserved in the four desaturases and one histidine residue that is not conserved were replaced by arginine, and the mutated desA genes were overexpressed in Escherichia coli. All of these mutations eliminated the delta 12 desaturase activity. These results demonstrate that the five histidine residues are essential for the activity of the delta 12 desaturase, perhaps by providing the ligands for the catalytic Fe center. PMID- 7890028 TI - DNA methyltransferase activity in the early stages of a sea urchin embryo. Evidence of differential control. AB - The specific activity of DNA methyltransferase increases in the nuclei of Sphaerechinus granularis sea urchin embryos at increasing stages of development. The activity reaches maximal value at about 20 h of growth, when embryos are at the mesenchyme blastula stage, then abruptly decreases and is essentially zero at about 35 h of development, when embryos are at the early gastrula stage. Both the increase and the drop of the activity are faster than embryonic cell duplication indicating that the enzyme is under strict control during development and that, in the more advanced embryo, a mechanism is activated to specifically block its activity. PMID- 7890029 TI - Stimulatory effect of unsaturated fatty acids on the level of plasminogen activator inhibitor-1 mRNA in cultured human endothelial cells. AB - To determine whether unsaturated fatty acids induce changes in the mRNA level of plasminogen activator inhibitor type-1 (PAI-1), Northern analyses were performed on human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells that were treated with two common fatty acids. Supplementation of cultured HUVEC with docosahexanoic acid (DHA) or with dihomogamma linolenic acid (DGLA), resulted in a concentration dependent, specific increase of the PAI-1 transcript levels, which was detectable within 2 h. DHA and DGLA treatment of smooth muscle cells did not result in changes in the PAI-1 mRNA levels. Homology search of the upstream regulatory region of the PAI-1 gene sequences identified a consensus nucleotide sequence for a fatty acid-responsive element. Our results indicate that unsaturated fatty acids selectively increase PAI-1 mRNA levels in endothelial cells, the primary source of circulating PAI-1 in vivo. PMID- 7890030 TI - Bicarbonate ions and pH regulation of Leishmania major promastigotes. AB - Leishmania major promastigotes are parasites endowed with a plasma membrane electrogenic H+ pump and anionic channels. These systems have been thought to contribute to pH homeostasis of parasites and environmental adaptation by mediating extrusion of protons which are either generated metabolically or result from exogenous acid loads. In this work we show that HCO-3 transport plays a physiological role in supporting pH regulation of parasites. Intracellular pH (pHi) and the membrane potential (Vm) were assessed fluorometrically with pH sensitive and potentiometric dyes. We show that intracellular acidification, caused either by blocking the pump or the putative anion channel or by depleting Cl- from cells, could be largely overcome by addition of HCO-3. Likewise, addition of HCO-3 raises the steady state intracellular pH of untreated cells from 6.76 +/- 0.01 to 6.98 +/- 0.02 and induces membrane hyperpolarization in pump-inhibited cells. We provide evidence for the involvement of HCO-3 transport systems that subserve pH homeostasis in Leishmania promastigotes. A major anionic pathway which is sensitive to anion transport blockers is apparently conductive in nature and accomodates ions such as HCO-3 and Cl-. In physiological conditions, the primary role of H+ pumping is the generation of a relatively large membrane potential (Vm = -113 +/- 4 mV) which subserves electrochemical driven uptake of nutrients. The involvement of H+ pumping in physiological pH regulation of promastigotes is apparently of a secondary nature. PMID- 7890031 TI - A comment on 'Endogenous fusicoccin-like ligand revealed in higher plants by radioreceptor and radioimmunoassays', by Aleksei V. Babakov et al. (1994) FEBS Lett. 351, 243-245. PMID- 7890032 TI - Molecular cloning and functional expression of a novel potassium channel beta subunit from human atrium. AB - We report the cloning and functional expression of a novel K+ channel beta subunit from human atrium, hKv beta 3. hKv beta 3 is highly homologous to the two beta-subunits cloned from rat brain, Kv beta 1 and Kv beta 2, but has an essentially unique stretch of 79 N-terminal residues. Upon expression in Xenopus oocytes, hKv beta 3 accelerates the inactivation of co-injected hKv1.4 currents and induces fast inactivation of non-inactivating co-injected hKv1.5 currents. By contrast, hKv beta 3 had no effect on hKv1.1, hKv1.2, or hKv2.1 currents. Thus, hKv beta 3 represents a third type of K+ channel beta-subunit which modulates the kinetics of a unique subset of channels in the Kv1 subfamily. PMID- 7890033 TI - Molecular evolution of receptors for eicosanoids. AB - The amino acid sequences of the receptors for various prostaglandins, thromboxane and lipoxin, which belong to the rhodopsin family, were aligned, and a phylogenetic tree was constructed to infer the evolutionary history of the arachidonic acid cascade. The obtained tree suggested that the origin of the cyclooxygenase pathway was different from that of the lipoxygenase pathway. The receptors involved in the cyclooxygenase pathway constructed an independent cluster, but the lipoxin A4 receptor, which is involved in the lipoxygenase pathway, belonged to the cluster of peptide receptors. The primitive form of the cyclooxygenase pathway had been a signal transduction system composed of prostaglandin E2 and its receptor associated with cAMP metabolism. PMID- 7890034 TI - Superoxide dismutase and glutathione peroxidase activities are increased by enalapril and captopril in mouse liver. AB - We have characterized the effect of angiotensin converting enzyme (ACE) inhibitors on the activity of CuZn-superoxide dismutase (CuZn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase, and selenium-dependent glutathione peroxidase (Se GPx). CF1 mice (4-month-old females) were administered water containing enalapril (20 mg/l) or captopril (50 mg/l), during 4 to 11 weeks. After 11 weeks, enalapril treatment caused an increase in the activity of CuZn-SOD, Mn-SOD and Se-GPx, from 19 +/- 4 to 46 +/- 7, 2.1 +/- 0.2 to 3.8 +/- 0.2 units/mg protein and 27 +/- 3 to 54 +/- 3 milliunits/mg protein, respectively. After 11 weeks, captopril treatment increased the activities (P < 0.05) of CuZn-SOD, MnSOD and Se-GPx to 35 +/- 4, 2.9 +/- 0.2 units/mg protein, and 38 +/- 2 milliunits/mg protein, respectively. Catalase activity was not affected by the treatments. These results suggest that ACE inhibitors may protect cell components from oxidative damage by increasing the enzymatic antioxidant defenses. PMID- 7890035 TI - Effects of mutations at position 36 of tRNA(Glu) on missense and nonsense suppression in Escherichia coli. AB - Mutations in the anticodon of tRNA(Glu) (UUC) were isolated or constructed and characterized for their ability to suppress cognate nonsense or missense mutations in vivo. The C36-to-A36 transversion mutation was isolated as an ochre and an amber suppressor, while the G36 transversion was selected as a CAG missense suppressor. tRNA(Glu) suppressors of an AAG missense mutation could not be isolated, and a U36 transition mutation introduced into tRNA(Glu) in vitro conferred no suppressor phenotype. Over-expression of glutamyl-tRNA synthetase did not increase the activity of the U36 mutant tRNA(Glu), suggesting a defect at the level of translation rather than at the level of synthetase recognition. PMID- 7890036 TI - Native like structure and stability of apo AI in a n-propanol/water solution as determined by 13C NMR. AB - To elucidate the molecular details of the conformation of apolipoprotein AI (apo AI), we have developed an approach related to the solubilization of this protein in 30% n-propanol. We have previously reported the promotion of a native-like structure for apo AI solubilized in n-propanol, as depicted by circular dichroism, fluorescence, and limited proteolytic digestion as compared to the lipid associated form of apo AI. In the present study, we labeled the Lys residues of apo AI with 13C by reductive methylation and used 13C NMR to confirm the formation of a native-like structure of apo AI in this environment. Furthermore, by the above criteria (circular dichroism and 13C NMR) and by using urea and temperature as denaturing agents, we show that the denaturation of the native-like structure of apo AI in n-propanol is a biphasic process. These studies show that in 30% n-propanol, apo AI contains two independently folded structural domains, of markedly different stabilities that might correspond to the amino-terminal and the carboxy-terminal halves of the molecule. PMID- 7890037 TI - Transit sequence-dependent binding of the chloroplast precursor protein ferredoxin to lipid vesicles and its implications for membrane stability. AB - The binding of the transit peptide (trfd) and precursor of the chloroplast protein ferredoxin (prefd) to large unilamellar lipid vesicles was investigated in relation to the lipid composition of the bilayer. Prefd binds with a dissociation constant of 0.27 microM to vesicles with a composition corresponding to the chloroplast envelope outer membrane. Binding is mediated by the transit sequence. From an analysis of binding to vesicles containing the individual lipid components it could be concluded that anionic lipids are mainly responsible for binding, emphasizing the importance of electrostatics for the transit sequence lipid interaction. Binding is also mediated by the specific chloroplast glycolipid monogalactosyldiacylglycerol. Monolayer experiments revealed that in this case a more extended domain of the transit sequence inserts into the lipid layer. Precursor binding does not result in a loss of vesicle barrier function. However, high concentrations of trfd do cause release of vesicle-enclosed carboxyfluorescein. The results are discussed in the light of the chloroplast protein import process, with special emphasis on the role of monogalactosyldiacylglycerol. PMID- 7890038 TI - Effects of lovastatin on adenylyl cyclase activity and G proteins in GH4C1 cells. AB - We studied the effect of lovastatin, a cholesterol lowering drug, on the basal state of G-proteins in GH4C1 cells. Our data show that the addition of lovastatin markedly decreased the amount of the alpha-subunits of the Gs and Gi-proteins in the plasma membrane. The decrease of alpha s was correlated with a decrease in adenylyl cyclase activity, and both effects were reverted by the presence of mevalonate. As the attachment of G protein subunits to the membrane is dependent on gamma-subunit prenylation, we assume that the mechanism through which lovastatin exerts its effects on G-proteins is the lack of mevalonate for the synthesis of prenyl residues. In conclusion, our data indicate that some of the effects of lovastatin are mediated through changes in the basal state of G protein in the membrane and consequently on adenylyl cyclase activity. PMID- 7890039 TI - Wortmannin inhibits insulin-stimulated but not contraction-stimulated glucose transport activity in skeletal muscle. AB - In skeletal muscle, glucose transport is stimulated by insulin, contractions and hypoxia. In this study, we used the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin to examine whether (i) PI 3-kinase activity is necessary for stimulation of glucose transport by insulin in muscle, and (ii) PI 3-kinase mediates a step in the pathway by which contractions/hypoxia stimulate glucose transport. Wortmannin completely blocked insulin- and insulin-like growth factor 1-stimulated glucose transport in muscle. In contrast, wortmannin had no effect on the stimulation of glucose transport by contractions or hypoxia, providing evidence that PI 3-kinase activity is not involved in the activation of glucose transport by these stimuli. PMID- 7890040 TI - In vitro dissociation of self-assembly of three chaperonin 60s: the role of ATP. AB - A comparative study has investigated the in vitro dissociation and self-assembly of chaperonin 60 14-mers isolated from E. coli (GroEL), yeast mitochondria and pea chloroplasts. In all cases Mg2+ inhibits, and low temperature stimulates, the urea-induced dissociation. ATP or ADP in the presence of Mg2+ enhance the dissociation of the chaperonins. Re-assembly of the 14-mers from their monomers shows different efficiencies between the three proteins. In all cases, however, self-assembly is stimulated by Mg-adenine nucleotides. Surprisingly, effective self-assembly of GroEL is promoted by 20% glycerol in the absence of ATP. The role of Mg-adenine nucleotides in the dissociation and assembly of the chaperonins is discussed. PMID- 7890041 TI - The extracellular matrix produced by bovine corneal endothelial cells contains progelatinase A. AB - Progelatinase A is a matrix metalloproteinase involved in the turnover of extracellular matrix (ECM). We report that the ECM produced by bovine corneal endothelial (BCE) cells contains progelatinase A free of tissue inhibitor of metalloproteinase (TIMP2). The matrix-bound progelatinase A can be activated by APMA to generate a 62 kDa and a 45 kDa species with enzymatic activity and is inhibited by TIMP2. The bound progelatinase can be released after treatment of the ECM with gelatinase B. These studies suggest that the ECM can function as a reservoir for progelatinase A which may be readily available for cells in processes such as metastasis, angiogenesis, inflammation and wound healing. PMID- 7890042 TI - kappa-Opioid receptor-transfected cell lines: modulation of adenylyl cyclase activity following acute and chronic opioid treatments. AB - The opioid receptors mu, delta and kappa have recently been cloned. Here we show that kappa-agonists inhibit adenylyl cyclase activity in Chinese hamster ovary cells stably transfected with rat kappa-opioid receptor cDNA. Chronic exposure of the cells to kappa-agonists did not lead to significant desensitization of the capacity of the agonists to inhibit adenylyl cyclase. On the other hand, withdrawal of the agonist following the chronic treatment led to the phenomenon of supersensitivity ('overshoot') of adenylyl cyclase activity. Both the inhibition of adenylyl cyclase activity by the acute opioid treatment and the chronic agonist-induced supersensitivity are pertussis toxin sensitive, demonstrating involvement of Gi/Go proteins in both processes. PMID- 7890043 TI - Electrochemical study of the redox properties of [2Fe-2S] ferredoxins. Evidence for superreduction of the Rieske [2Fe-2S] cluster. AB - Direct, unmediated electrochemistry has been used to compare the redox properties of [2Fe-2S] clusters in spinach ferredoxin, Spirulina platensis ferredoxin and the water soluble fragment of the Rieske protein. The use of electrochemistry enabled, for the first time, the observation of the second reduction step, [Fe(III), Fe(II)] to [Fe(II), Fe(II)], in a biological [2Fe-2S] system. A water soluble fragment of the Rieske protein from bovine heart bc1 complex exhibits two subsequent quasi-reversible responses in cyclic voltammetry on activated glassy carbon. In contrast the ferredoxins from spinach and Spirulina platensis only show one single reduction potential. These results support a seniority scheme for biological iron-sulfur clusters related cluster size to electron transfer versatility. Electrochemical reduction of spinach ferredoxin in the presence of NADP+ and ferredoxin: NADP+ oxidoreductase results in the generation of NADPH. The second order rate constant for the reaction between the ferredoxin and the reductase was estimated from cyclic voltammetry experiments to be > 3.10(5) M-1.s 1. PMID- 7890044 TI - Wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase, blocks osteoclastic bone resorption. AB - The biological role of phosphatidylinositol (PI)-3 kinase was examined in osteoclast-like multinucleated cells (OCLs) formed in co-cultures of mouse osteoblastic cells and bone marrow cells. The expression of PI-3 kinase in OCLs was confirmed by Western blot analysis. Wortmannin (WT), a specific inhibitor of PI-3 kinase, inhibited PI-3 kinase activity in OCLs both in vitro and in vivo. WT also inhibited pit-forming activity on dentine slices and disrupted a ringed structure of F-actin-containing dots (an actin ring) in OCLs in a dose-dependent manner. The inhibitory profiles of WT for pit and actin ring formation were similar to that for PI-3 kinase activity in OCLs. Electron microscopic analysis revealed that OCLs treated with WT did not form ruffled borders. Instead, numerous electron lucent vacuoles of differing sizes were found throughout the cytoplasm. These results suggest that PI-3 kinase is important in osteoclastic bone resorption. PMID- 7890045 TI - An N-terminal hydrophobic peak is the sorting signal of regulated secretory proteins. AB - Endocrine and exocrine cells each contain a regulated and constitutive secretory pathway. The presence of two distinct secretory pathways in the same cell type requires a sorting step to direct secretory proteins to the correct pathway. It is thought that regulated secretory proteins contain a specific sorting signal. However, this signal has not been identified. Amino acid sequence comparisons have not revealed any significant similarity between different regulated secretory proteins, suggesting that the sorting signal does not consist of a conserved primary sequence. In the present report, we have analyzed the predicted secondary structures of regulated secretory proteins and identified an N-terminal hydrophobic peak (NHP) which is located approximately from amino acids 9-26, overlaps with a predicted alpha-helix and contains charged amino acid residues. This signal is present in regulated secretory proteins that exhibit an N-terminal sorting sequence, but it is absent from constitutively secreted proteins and proteins where the sorting sequence is not located near the N-terminus. It appears that the NHP is both necessary and sufficient for sorting of many secretory proteins to the regulated secretory pathway. PMID- 7890046 TI - Use of a constrain phage displayed-peptide library for the isolation of peptides binding to HIV-1 nucleocapsid protein (NCp7). AB - It has been shown that peptide libraries are powerful tools for the identification of peptides showing new binding specificity. This technology was applied to the isolation of peptides binding to HIV-1 nucleocapsid protein (NCp7). Three different prolin reach peptide sequences, interacting with NCp7, were isolated, from a constrained phage displayed-peptide library of 10(8) independent clones. The three peptide sequences, isolated from the peptide library, were shown to bind NCp7 in the region 30-52. Moreover, two of them share the PP-(D/E)R consensus sequence. PMID- 7890047 TI - Inhibition of the DNA-binding activity of NF-kappa B by gold compounds in vitro. AB - Nuclear factor kappa B (NF-kappa B) is a transcription factor that is critical for the inducible expression of multiple cellular and viral genes. DNA binding activity is essential for its function. Here, we report that gold compounds, especially aurothioglucose (AuTG), have a strong inhibitory effect on NF-kappa B DNA binding. Our finding also reveals that Zn2+ is a necessary component of NF kappa B for its DNA binding activity and that gold ion can efficiently block NF kappa B-DNA binding, presumably through oxidation of the cysteins associated with zinc. This redox mechanism may provide an explanation for the observed efficacy of gold compounds in the treatment of rheumatoid arthritis. PMID- 7890048 TI - Specific arrangement of three amino acid residues for flavin-binding barrel structures in NADH-cytochrome b5 reductase and the other flavin-dependent reductases. AB - The structure of NADH-cytochrome b5 reductase from pig liver microsomes has been refined to a crystallographic R factor of 0.223 at 2.4 A resolution. A structural comparison between the flavin-binding beta barrel domain of NADH-cytochrome b5 reductase and those of the other flavin-dependent reductases, ferredoxin-NADP+ reductase, phthalate dioxygenase reductase and nitrate reductase, indicated that the overall barrel foldings are similar to each other and that the specific arrangement of three amino acid residues (Arg, Tyr and Ser/Thr) is usually necessary for flavin-binding. These conserved residues overlap each other in their three-dimensional structures and stabilize the flavin-binding site in the four flavin-dependent reductases. PMID- 7890049 TI - Pharmacokinetics of follicle-stimulating hormone: clinical significance. AB - OBJECTIVE: To review studies that examine the pharmacokinetics and pharmacodynamics of endogenous, as well as several exogenous FSH preparations. DESIGN: Related studies were identified through a computerized bibliographic search. PATIENTS: Initial pharmacodynamic studies were done in animal models and in women and men with either hypogonadotropic hypogonadism or suppressed hypothalamic-pituitary-gonadal axis. More recent studies evaluated FSH pharmacokinetics during ovulation induction treatment in women with normal ovulatory cycles or polycystic ovarian syndrome. RESULTS: Various types of FSH exist according to their sialic acid content. High estrogen levels induce the secretion of less sialylated molecules with higher receptor affinity and an increased clearance rate. It appears that there is a threshold FSH level that should be reached to achieve an ovarian response. A very narrow range exists between the threshold and ceiling level for monofollicular growth. This threshold level is surpassed intentionally during IVF treatment cycles to induce multiple follicular recruitment. The threshold level can change under situations such as polycystic ovaries, perimenopause, oral contraceptives, and GnRH analogue treatment. CONCLUSIONS: To avoid the risk of ovarian hyperstimulation syndrome and multiple pregnancies, careful adjustments of serum FSH levels should be made by fine dosage modifications. By monitoring FSH levels and using less sialylated preparations, the efficacy of the treatment probably will improve. PMID- 7890050 TI - Twins or more. PMID- 7890051 TI - Single-stage total hysteroscopic myomectomies: indications, techniques, and results. AB - OBJECTIVE: To assess the risks and benefits of myomectomies performed by endouterine resection. DESIGN: A retrospective analysis of 284 patients, with histologically proven submucous myomas, operated on between April 1984 and April 1993. Outcomes were analyzed by Kaplan-Meier statistics. SETTING: Author's private practice in University Medical Center. PATIENTS: The age ranged from 25 to 70 years. INTERVENTIONS: All the interventions but one were performed entirely at one setting. Myomas ranged in diameter from 10 to 65 mm. MAIN OUTCOME MEASURES: Clinical symptoms and hysteroscopic appearance. RESULTS: Good anatomical and functional results were achieved in 95.6% of cases during the first 6 postoperative months, persisting in 94.6% at 1 year, in 89.7% at 2 years, in 87.8% at 3 years, in 83.0% at 4 years, in 76.3% at 5 years, in 73.2% at 6 years, and remained stable at 67.6% by > or = 7 years. The only notable complication was one perforation, which was repaired immediately. Endouterine resection did not improve the outcome in patients with primary infertility but was of benefit in cases of secondary infertility. CONCLUSIONS: Myomectomy by endouterine resection is a difficult but safe and worthwhile conservative intervention. PMID- 7890052 TI - The efficacy of Interceed(TC7)* for prevention of reformation of postoperative adhesions on ovaries, fallopian tubes, and fimbriae in microsurgical operations for fertility: a multicenter study. Nordic Adhesion Prevention Study Group. AB - OBJECTIVE: To evaluate the efficacy of Interceed as an adjuvant in the prevention of postoperative adhesion reformation to the ovary, fallopian tube, and fimbria when used together with microsurgical techniques. DESIGN: Prospective, randomized, multicenter, controlled clinical study. SETTING: Normal human volunteers in an academic research environment. PATIENTS: Sixty-six women suffering from infertility due at least in part to bilateral tubal disease with bilateral adhesions attached to ovaries, fallopian tubes, and fimbriae. INTERVENTION: Adhesiolysis bilaterly through laparotomy with microsurgical techniques, application of Interceed on one of the sides randomly assigned not known by the surgeon before application, follow-up laparoscopy 4 to 10 weeks postoperatively, with each patient serving as her own control. MAIN OUTCOME MEASURES: Adhesion severity scores at all sites and number of adhesion free organs after laparotomy and follow-up laparoscopy. RESULTS: When the initial scores registered at the operation for fertility were compared with those registered at the second-look laparoscopy, the results indicated that gentle microsurgical techniques resulted in a significant reduction of postoperative adhesions. Adnexa, which were covered with Interceed, had significantly lower adhesion scores than the control adnexa, representing an improvement of 39% compared with microsurgery alone (control) in reducing adhesion reformation scores. When combined with microsurgical techniques, Interceed reduced adhesion reformation scores by 70%. The number of ovaries, fallopian tubes, and fimbriae without adhesions at the time of second-look laparoscopy was significantly increased by approximately twofold when organs were covered with Interceed. CONCLUSION: In a prospective, randomized, multicenter, controlled clinical study using a protocol in which other adjuvants have been shown not to be efficacious, Interceed was shown to reduce significantly the incidence and severity of adhesion reformation to the ovary, fallopian tube, and fimbria after infertility surgery. PMID- 7890053 TI - Salpingitis isthmica nodosa: results of transcervical fluoroscopic catheter recanalization. AB - OBJECTIVE: To investigate the role of transcervical tubal catheterization in diagnosis and treatment of proximal tubal obstruction associated with salpingitis isthmica nodosa. DESIGN: Retrospective case study. SETTING: University hospital and outpatient radiology practice. PATIENTS: Fifty-two women with proximal tubal obstruction associated with salpingitis isthmica nodosa. INTERVENTION: Selective salpingography and catheter recanalization using fluoroscopic guidance. MAIN OUTCOME MEASURES: The number of tubes visualized to the fimbria as a percentage of the tubes with proximal tubal obstruction on the initial hysterosalpingogram was determined as a measure of diagnostic efficacy. To evaluate the treatment potential of catheter recanalization, the patients were grouped according to tubal status at the conclusion of the procedure and subsequent pregnancies were evaluated. RESULTS: Forty-seven of 65 tubes (72%) with proximal tubal obstruction were recanalized successfully. Among the 19 women who were able to conceive only via a recanalized salpingitis isthmica nodosa tube, there were 6 live births (32%) and two tubal pregnancies (10%). CONCLUSION: Selective salpingography allows complete tubal diagnosis in almost three fourths of patients with proximal tubal obstruction and salpingitis isthmica nodosa. The radiographic diagnosis of salpingitis isthmica nodosa may be pressure dependent. Intrauterine pregnancies occur via recanalized salpingitis isthmica nodosa tubes, therefore catheter recanalization may be attempted before tubal microsurgery or IVF in patients with proximal tubal obstruction and associated salpingitis isthmica nodosa. PMID- 7890054 TI - Preimplantation genetic diagnosis for Tay-Sachs disease: successful pregnancy after pre-embryo biopsy and gene amplification by polymerase chain reaction. AB - OBJECTIVE: To determine the ability to apply preimplantation genetic diagnostic techniques to screen for and prevent Tay-Sachs disease (TSD). DESIGN: A couple, both carriers for the 4 base pair (bp) insertion in exon 11 of the beta hexosaminidase A gene, which results in TSD, underwent IVF, pre-embryo biopsy, polymerase chain reaction (PCR) DNA amplification of the biopsied blastomeres, and pre-embryo transfer. One to two blastomeres were aspirated using a biopsy pipette that was inserted through an opening in the zona formed with acidified phosphate buffer. Polymerase chain reaction was performed on the individual blastomeres for 20 cycles followed by an additional 30 cycles using nested primers. This yielded amplified DNA products of 272 and 276 bp for the normal and mutant gene, respectively. Heteroduplex formation was used for identification of normal, homozygous affected, and heterozygous pre-embryos. RESULTS: Seven of 13 oocytes fertilized normally and were biopsied at the four- to eight-cell stages. Deoxyribonucleic acid amplification occurred in four of seven pre-embryos (one homozygous affected and three homozygous normal pre-embryos). The three normal pre-embryos that continued to cleave after biopsy were transferred on the evening of day 3 after retrieval. Subsequently, a single gestational sac was observed and the genetic diagnosis was confirmed at amniocentesis. CONCLUSION: A successful pregnancy and birth were accomplished after preimplantation genetic diagnostic screening for the prevention of TSD. PMID- 7890055 TI - A comparative prospective study of conventional regimen with chronic low-dose administration of follicle-stimulating hormone for anovulation associated with polycystic ovary syndrome. AB - OBJECTIVE: To compare efficiency of conventional and chronic low-dose regimens for treatment of anovulation associated with polycystic ovary syndrome (PCOS). DESIGN: Fifty participants divided into two equal groups. The first group was treated with urinary human FSH using a conventional stepwise protocol and the second group was treated with a regimen of chronic low-dose and small incremental rises with urinary human FSH or with recombinant human FSH for a maximum of three cycles. SETTING: Tertiary referral university hospital fertility unit. PATIENTS: Fifty infertile women with clomiphene citrate-resistant anovulation associated with PCOS. MAIN OUTCOME MEASURES: Pattern of follicular development, amount of FSH required, serum E2 concentrations, cycle fecundity, cumulative conception, and live birth rates. Multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) rates. RESULTS: Compared with the conventional dose protocol, the chronic low-dose regimen yielded slightly improved pregnancy rates (40% versus 24%) while completely avoiding OHSS and multiple pregnancies, which were prevalent (11% and 33%, respectively) with conventional therapy. Monofollicular development was induced in 74% versus 27% of cycles, and the total number of follicles > 16 mm and E2 concentrations were half those observed on conventional therapy. CONCLUSIONS: For women with PCOS, a chronic low-dose regimen of FSH eliminated complications of OHSS and multiple pregnancies while maintaining a satisfactory pregnancy rate. This modality, thus, has distinct advantages and could well replace conventional gonadotropin therapy for these patients. PMID- 7890056 TI - Ovarian influence on adrenal androgen secretion in polycystic ovary syndrome. AB - OBJECTIVE: To determine whether the ovary influences adrenal androgen secretion in polycystic ovary syndrome (PCOS). DESIGN: The adrenal androgen secretion was evaluated before and during ovarian suppression with a long-acting GnRH agonist. SETTING: Department of Obstetrics and Gynecology, Pisa, Italy. PARTICIPANTS: Women with PCOS and high (10 subjects) and normal (12 subjects) DHEAS levels and 6 normal women. INTERVENTIONS: After 1 mg dexamethasone, an ACTH-(1-24) stimulation test was performed in the early follicular phase of the menstrual cycle. The test was repeated after two injections of a long-acting GnRH analogue (GnRH-a). MAIN OUTCOME MEASURES: Basal plasma levels of gonadotropins, E2, T, androstenedione (A), 17 alpha-hydroxyprogesterone (17-OHP), DHEAS, and cortisol (F) were evaluated before the evening administration of dexamethasone. Serum A, T, 17-OHP, DHEAS, and F were measured 9 hours after dexamethasone and in samples collected 60 and 120 minutes after ACTH IV injection. RESULTS: In the high DHEAS group the maximum increases in T, A, 17-OHP, and DHEAS in response to ACTH were significantly higher than in normal DHEAS PCOS women and in normal women. The GnRH-a modified the A and T responses to ACTH in the high DHEAS group. CONCLUSIONS: Ovarian steroids, or other extra-ovarian factors, seem to be responsible for the increased A and T responses to the corticotropin stimulation demonstrated in some PCOS women. PMID- 7890058 TI - Low-dose growth hormone-releasing factor may enhance folliculogenesis in regularly menstruating women: a preliminary study. AB - OBJECTIVE: To evaluate the effect of low-dose GH-releasing factor (GRF) on folliculogenesis in regularly menstruating women. DESIGN: Prospective clinical trial where individual patients served as their own control. SETTING: Outpatient Reproductive Endocrine/Infertility Clinic of the Los Angeles County-University of Southern California Medical Center, Los Angeles, California. PATIENTS: Seven regularly menstruating women. INTERVENTION: During treatment cycles, subjects received 100 micrograms SC GRF on cycle days 2 to 11 and were observed during a control cycle. MAIN OUTCOME MEASURES: Follicle number and diameter, as well as endometrial thickness were all assessed by vaginal ultrasound and blood was obtained for serum FSH, LH, E2, P, GH, insulin-like growth factor 1 (IGF-1), and insulin-like growth factor binding protein-3. RESULTS: During cycles treated with GRF, GH, and IGF-1 levels were normal. However, follicular growth rates and E2 to FSH ratios were significantly higher. The day of the peak E2 to follicular diameter ratio after GRF was earlier than in control cycles. Endometrial growth rates were also greater with GRF. CONCLUSIONS: Our data, although preliminary, support the hypothesis that low doses of GRF may independently stimulate the ovary and enhance folliculogenesis. PMID- 7890057 TI - Prolonged gonadotropin-releasing hormone agonist treatment of symptomatic endometriosis: the role of cyclic sodium etidronate and low-dose norethindrone "add-back" therapy. AB - OBJECTIVE: To examine the safety and efficacy of combining cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH agonist (GnRH-a) for prolonged therapy of symptomatic endometriosis. DESIGN: Prospective randomized open label study. SETTING: Tertiary care university-affiliated reproductive medicine program. PATIENTS: Nineteen regularly cycling women with laparoscopically diagnosed symptomatic endometriosis and 18 regularly cycling untreated controls without endometriosis. INTERVENTIONS: All patients received a depot preparation of the GnRH-a leuprolide acetate IM monthly for 48 weeks. Group I patients (n = 10) received supplemental sodium etidronate cycled with calcium carbonate as well as 2.5 mg norethindrone daily. Group II patients (n = 9) received only supplemental 10 mg norethindrone daily. Group III volunteers (n = 18) were untreated and followed for bone density changes. MAIN OUTCOME MEASURES: Disease extent at follow-up laparoscopy; pain, vasomotor, and vaginal symptom scores; bone mineral density (serial dual-energy roentgenogram absorptiometry scans); serum estrogens, lipids, and glucose and insulin response to glucose challenge. RESULTS: Painful symptoms and extent of endometriosis were reduced in both treatment groups. Despite maintenance of a chronically hypoestrogenic state for 48 weeks, no changes in bone density over time or in comparison to group III untreated controls were noted. Similarly, no evidence of significant vasomotor symptoms were reported in either treatment group. However, adverse changes over time in circulating low-density lipoprotein (LDL) cholesterol and apolipoprotein A1 levels as well as the ratio of high-density lipoprotein to LDL were noted only in group II. CONCLUSIONS: The combination of cyclic sodium etidronate and low dose norethindrone with a long-acting GnRH-a served to safely prolong medical therapy of symptomatic endometriosis. Clinical efficacy was preserved while prophylaxis against significant hypoestrogenic side effects was achieved. PMID- 7890059 TI - Endometrial effects of long-term low-dose administration of RU486. AB - OBJECTIVE: To examine endometrial response to long-term low-does RU486 administration. DESIGN: Retrospective controlled study of women with endometriosis treated for 6 months with 50 mg RU486 daily for 6 months. Controls consisted of women in the follicular phase of a spontaneous cycle undergoing endometrial biopsy. SETTING: Patients from the clinical practice of the authors at the University of California, San Diego Medical Center. PATIENTS AND INTERVENTIONS: Nine patients treated with long-term low-dose RU486 and nine normal cycling controls undergoing hysterectomy or endometrial biopsy for benign disease. MAIN OUTCOME MEASURES: Changes in endometrial morphology and immunohistochemical analysis for estrogen receptor (ER) and progesterone receptor (PR) protein. RESULTS: All patients treated with RU486 exhibited abnormal endometrial morphology. The endometrial glands were irregular in size and shape. The stroma was varied but consisted predominantly of dense cellular stroma with frequent mitotic figures. The glands were lined by a combination of epithelial types some of which were secretory. No cytologic atypia was seen. Levels of ER immunoreactivity, as determined by image analysis, were greater in the stroma with no difference in PR immunoreactivity compared with controls. No difference in ER and PR immunoreactivity were seen in the glands compared with normal controls. CONCLUSION: The generalized cystic changes demonstrated are consistent with a chronic unopposed estrogen effect and are concordant with hormonal data showing early to midfollicular phase levels of estrogens. They also are consistent with our findings of increased ER immunoreactivity in the stroma. Evidence of minimal P agonist effect was noted. PMID- 7890060 TI - The effect of Norplant on glucose metabolism under hyperglycemic hyperinsulinemic conditions. AB - OBJECTIVES: To assess the impact of a levonorgestrel-releasing implant contraceptive (Norplant; Wyeth-Ayerst Laboratories, Philadelphia, PA) on glucose metabolism. DESIGN: Prospective evaluation of insulin action and secretion in women under hyperglycemic hyperinsulinemic clamp conditions in the midfollicular phase before and 8 weeks after Norplant placement. SETTING: Yale University Clinical Research Center. PARTICIPANTS: Seven previously normally cycling, nonobese, nondiabetic women participated in the study. INTERVENTIONS: Norplant insertion. MAIN OUTCOME MEASURES: Basal levels of glucose and insulin, as well as glucose-mediated insulin secretion, glucose uptake, and tissue sensitivity to insulin were assessed using the hyperglycemic hyperinsulinemic clamp technique before and after Norplant insertion. RESULTS: Norplant placement did not alter the fasting glucose or insulin levels. However, it was associated with a significant 37% increase in the first phase insulin response from a control level of 51 +/- 8 to 70 +/- 10 microU/mL (conversion factor to SI unit, 7.175), and a significant 48% increase in the second phase insulin response from 60 +/- 5 to 89 +/- 8 microU/mL. In association with this increase in insulin levels after Norplant insertion, total mean body glucose uptake (M) increased from 8.08 +/- 0.91 to 9.53 +/- 0.95 mg/kg per minute. However, when expressed as the total body glucose uptake per unit of insulin, the M:I ratio (a measure of tissue sensitivity to insulin) decreased significantly from a mean of 0.12 +/- 0.02 to 0.10 +/- 0.01 mg/kg per minute per microU/mL. CONCLUSION: Although Norplant insertion does not alter basal glucose and insulin levels, tissue sensitivity to insulin under hyperglycemic hyperinsulinemic conditions is decreased after Norplant insertion. PMID- 7890061 TI - Effect of intrauterine contraceptive devices on cytokine messenger ribonucleic acid expression in the human endometrium. AB - OBJECTIVE: To compare cytokine messenger RNA (mRNA) expression in the endometrium exposed to an intrauterine contraceptive device (IUD) and in normal cycling endometrium. DESIGN: Quantitative reverse-transcribed polymerase chain reaction was used to assess interleukin (IL) 1 beta, IL-6, tumor necrosis factor alpha (TNF-alpha), and colony-stimulating factor 1 (CSF-1) mRNA expression in endometrial tissue samples obtained by curettage or at hysterectomy from 11 women using a copper-releasing IUD, 10 women having a levonorgestrel-releasing IUD, and 13 fertile women during different phases of the menstrual cycle. RESULTS: The mRNAs encoding the studied cytokines were detected in all endometrial samples. The mean IL-1 beta, IL-6, and TNF-alpha mRNA levels were higher in the late secretory menstrual phase compared with the proliferative early secretory phase of the menstrual cycle both in endometria exposed to the copper IUD and in the control samples. The IL-1 beta and TNF-alpha mRNA levels were significantly higher in endometria exposed to the copper IUD compared with the control endometria in the late secretory menstrual phase, whereas no difference was found in the expression of these cytokine mRNAs during the proliferative early secretory phase. In contrast, the mean IL-6 mRNA level was higher in the copper IUD-exposed endometria than in the control endometria in the proliferative early secretory but not in the late secretory menstrual phase. In the levonorgestrel IUD-exposed endometria, the mean levels of IL-1 beta, TNF-alpha, and CSF-1 mRNA were similar to those in normal endometrium in the late secretory menstrual phase. The mean IL-6 mRNA level in levonorgestrel IUD-exposed endometria was lower than that in late secretory menstrual phase of controls but, because of a great individual variation in the control samples, the difference did not reach significance. No significant cyclic change nor any difference in relative CSF-1 mRNA levels between the three study groups was detected. CONCLUSIONS: These data provide the first evidence that the use of IUDs is associated with alterations in endometrial cytokine expression and that the alterations differ depending on the cytokine and the type of IUD. We speculate that cytokines are involved in intrauterine contraceptive effects of IUDs. PMID- 7890062 TI - A dopamine D3 receptor genotype is associated with hyperandrogenic chronic anovulation and resistant to ovulation induction with clomiphene citrate in female Hispanics. AB - OBJECTIVE: To determine if dopamine (D3) receptor genotypes are associated with anovulation and response to ovulation induction with clomiphene citrate. DESIGN: Clinical and laboratory characteristics of anovulatory patients and ovulatory controls were compared with findings at the DNA level. SETTING: An outpatient clinic at an university medical center. PATIENTS: One hundred eighty human Hispanic female volunteers (130 of these with documented ovulatory status) were studied. INTERVENTIONS: Genomic DNAs were extracted from each patient. Polymerase chain reaction with subsequent restriction digest was performed to analyze the D3 receptor allele status (two possible alleles). MAIN OUTCOME MEASURES: Menstrual history, serum T, and midluteal serum Ps from spontaneous and clomiphene cycles were correlated with D3 receptor genotype. RESULTS: Hispanic females with the 22 genotype compared with the other genotypes (11 and 12) were more likely to have irregular menses, an elevated serum T (> or = 70 ng/dL [conversion factor to SI unit, 3.467]), and hyperandrogenic chronic anovulation. These patients tended to be resistant to ovulation induction requiring a significantly higher dose of clomiphene to achieve an ovulatory response (22 genotype [mean +/- SEM] [140.0 +/ 19.0 mg] versus 11 [77.1 +/- 17.5 mg] or 12 [69.2 +/- 13.1 mg]). This effect was independent of patient age, weight, or serum T level. CONCLUSIONS: Hyperandrogenic chronic anovulation may have a genetic component. Genetic analysis may be useful in predicting resistance to ovulation induction with clomiphene. PMID- 7890063 TI - Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. AB - OBJECTIVE: To study the effect of E2 and P on the epithelial cell cycle of normal human breast in vivo. DESIGN: Double-blind, randomized study. Topical application to the breast of a gel containing either a placebo, E2, P, or a combination of E2 and P, daily, during the 10 to 13 days preceding breast surgery. PATIENTS: Forty premenopausal women undergoing breast surgery for the removal of a lump. MAIN OUTCOME MEASURES. Plasma and breast tissue concentrations of E2 and P. Epithelial cell cycle evaluated in normal breast tissue areas by counting mitoses and proliferating cell nuclear antigen immunostaining quantitative analyses. RESULTS: Increased E2 concentration increases the number of cycling epithelial cells. Increased P concentration significantly decreases the number of cycling epithelial cells. CONCLUSION: Exposure to P for 10 to 13 days reduces E2-induced proliferation of normal breast epithelial cells in vivo. PMID- 7890064 TI - Habitual abortion is accompanied by low serum levels of placental protein 14 in the luteal phase of the fertile cycle. AB - OBJECTIVE: To study serum levels of placental protein 14 (PP14) in relation to endometrial function in women with a history of habitual abortion. DESIGN: Prospective study. SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Helsinki, Finland. PATIENTS: Fifty patients (26 primary and 24 secondary habitual aborters) and 38 controls without a history of abortion studied during a regular cycle. RESULTS: Habitual aborters as a whole or when subgrouped into those with normal cycles (n = 40) or with a luteal phase defect (LPD; n = 10) and control women demonstrated a distinct increase in PP14 levels from late follicular to late luteal phases. In the luteal phase, serum PP14 levels were lower in the patients than in the controls (27.2 +/ 3.1 versus 48.5 +/- 10.1 micrograms/L), but the differences in PP14 levels between habitual aborters with or without LPD was not significant (16.3 +/- 4.3 versus 29.9 +/- 3.7 micrograms/L). CONCLUSIONS: Habitual aborters exhibit lower serum PP14 levels in the late luteal phase compared with normal fertile women. PMID- 7890065 TI - Endometriosis, pelvic pain, and psychological functioning. AB - OBJECTIVE: To investigate whether there are psychological differences between women with symptomatic as opposed to asymptomatic mild endometriosis. DESIGN: Forty-nine women with minimal or mild endometriosis completed the Beck Depression Inventory, the Speilberger State-Trait analysis, and the Golombok Rust Inventory of Sexual Satisfaction. Women admitted for sterilization acted as normal controls and women complaining of pelvic pain with no organic pathology were studied also. SETTING: Tertiary referral centers for endometriosis. MAIN OUTCOME MEASURES: Women with pelvic pain symptoms, whether they had mild endometriosis or a normal pelvis, had similar scores for the Beck Depression Inventory. These scores were significantly higher than those of women with asymptomatic disease and normal women admitted for sterilization. CONCLUSIONS: Women with mild endometriosis should not be included as a control group when studies on pelvic pain are planned. PMID- 7890066 TI - Reactions to infertility based on extent of treatment failure. AB - OBJECTIVE: To examine the relationship between amount of treatment failure and personal and marital distress. DESIGN: In this cross-sectional design, three groups of women (n = 91) with varying amounts of treatment failure experience were compared on measures of general and infertility-related distress and marital and sexual distress. RESULTS: The relationship between treatment failure experience and personal and marital distress was found to be curvilinear. The group that had a moderate amount of treatment failure experienced the most distress whereas the distress level of those without or with a high amount of treatment failure experience was comparable. The results also showed that the relationship between amount of treatment failure and distress was independent of age, years infertile, or years in treatment. CONCLUSION: The findings of this study provide support for infertility theories that suggest that infertility is a process rather than a series of independent emotional events and suggest that the distress women experience during infertility is a necessary part of their evolution toward acceptance of their infertility. PMID- 7890067 TI - Using ejaculated, fresh, and frozen-thawed epididymal and testicular spermatozoa gives rise to comparable results after intracytoplasmic sperm injection. AB - OBJECTIVE: To describe the preparation of fresh or frozen-thawed epididymal and testicular sperm for intracytoplasmic single sperm injection and to compare the fertilization, embryo quality, and pregnancy rates (PRs) obtained after using these spermatozoa to the results when freshly ejaculated sperm was used for microinjection. DESIGN: Retrospective analysis of 1,034 consecutive microinjection cycles. Ejaculated (965 cycles), fresh epididymal (43 cycles), frozen-thawed epididymal (9 cycles), and testicular sperm (17 cycles) was used for intracytoplasmic sperm injection. SETTING: Procedures were performed in a tertiary IVF center coupled with an institutional research environment. MAIN OUTCOME MEASURES: Semen density and motility were judged by the World Health Organization criteria and sperm morphology was evaluated by the Tygerberg's strict criteria. After microinjection, oocyte intactness, fertilization, embryo cleavage, transfer, and PRs were evaluated and compared. RESULTS: The median values of total sperm count, total motility and normal morphology were 17.85 x 10(6), 37%, 8% for freshly ejaculated sperm; 46.20 x 10(6), 12%, 9% for fresh epididymal sperm; 0.15 x 10(6), 0%, 0% for frozen-thawed epididymal sperm; and 0.54 x 10(6), 0% for testicular sperm (morphology was not determined). The percentage of intact oocytes after microinjection ranged from 84% to 90%. Normal fertilization rates were high when fresh or frozen-thawed epididymal and testicular spermatozoa were used for the injection (56%, 56%, 48%, respectively) but were significantly lower than for ejaculated sperm (70%). There was a higher proportion of transferable embryos obtained after ejaculated sperm injection than after testicular sperm injection. Forty percent, 58%, 33%, and 46% of cycles had positive serum hCG using ejaculated, fresh, or frozen-thawed epididymal and testicular sperm. Initial pregnancy loss occurred in 26.3% of the conception cycles. CONCLUSION: Intracytoplasmic sperm injection can provide high normal fertilization, cleavage, and PRs when fresh or frozen-thawed epididymal and testicular spermatozoa are used, but normal fertilization rates are significantly lower than after microinjection with ejaculated sperm. PMID- 7890068 TI - Late intracytoplasmic sperm injection in unexpected failed fertilization in vitro: diagnostic or therapeutic? AB - OBJECTIVE: To evaluate fertilization potential of 24-hour-old unfertilized oocytes using intracytoplasmic sperm injection and the pregnancy potential of resultant embryos. DESIGN: Prospective observational study. SETTING: Private infertility clinic, London, United Kingdom. PATIENTS: Fifteen patients with a history of infertility who underwent treatment with IVF and showed failure of fertilization on the day after oocyte retrieval. INTERVENTION: Assisted fertilization with intracytoplasmic sperm injection was carried out at 24 hours after oocyte retrieval. RESULTS: A total of 121 metaphase II oocytes were subjected to intracytoplasmic sperm injection. Of these, 9 were damaged (7%), 2 were polyploidic (2%), and 58 showed normal fertilization (48%). Of the latter, 47 cleaved normally (81%). Forty embryos were transferred and three were cryopreserved. One patient conceived (7%) but in this case only one of three embryos transferred was from intracytoplasmic sperm injection. CONCLUSION: Late (24 hours) intracytoplasmic sperm injection can give good fertilization and cleavage rates but the potential of the generated embryos to achieve pregnancy seems to be low. PMID- 7890069 TI - Practical evolution and application of direct intracytoplasmic sperm injection for male factor and idiopathic fertilization failure infertilities. AB - OBJECTIVE: To analyze the introduction of a new assisted fertilization technique for the treatment of severe male factor and idiopathic fertilization failure infertilities. DESIGN: Retrospective analysis of 16-month clinical application of IVF-ET where insemination was performed solely by direct intracytoplasmic sperm injection. SETTING: Clinical IVF-ET program. PATIENTS: Ninety-two couples undergoing 105 cycles of sperm injection. RESULTS: One hundred embryo transfers yielded 28 viable pregnancies (28%) from which eight normal deliveries have occurred to date. Complete cleavage arrest or fertilization failure occurred in four cycles, and one couple had all embryos cryopreserved. One thousand one hundred forty-three eggs were injected of which 173 (15%) degenerated. Four hundred seventy-nine of the surviving 970 eggs became normally fertilized (49%), and 381 of these zygotes (79.5%) developed suitably for cryopreservation or for transfer. Thirty-four of 310 embryos transferred implanted, yielding an implantation rate of 11%. Both testicular and epididymal sperm were used successfully to achieve fertilization and pregnancies, as was sperm retrieved by electroejaculation. Older women and couples suffering from prior idiopathic fertilization failure had a markedly poorer outcome. CONCLUSIONS: These results confirm that the intracytoplasmic sperm injection technique is a successful form of assisted fertilization that can be applied to a wide range of couples at significant risk from fertilization failure. PMID- 7890070 TI - Factors of importance for the establishment of a successful program of intracytoplasmic sperm injection treatment for male infertility. AB - OBJECTIVE: To establish an intracytoplasmic sperm injection treatment program for couples with male infertility and to determine those factors important for success. DESIGN: A retrospective analysis of 171 consecutive cycles of intracytoplasmic sperm injection concerning 145 infertile couples. SETTING: Infertility clinic in a private hospital associated with a university hospital. PATIENTS: Couples with infertility in the male partner whose sperm parameters were unacceptable for conventional IVF or in whom fertilization by conventional IVF failed repeatedly. INTERVENTIONS: One hundred seventy-one transvaginal oocyte retrievals were completed after superovulation with GnRH agonist and gonadotropins. MAIN OUTCOME MEASURES: The parameters evaluated included fertilization, cleavage, implantation, pregnancy, and spontaneous abortion in relation to patient indications and improved procedures. RESULTS: After intracytoplasmic sperm injection, normal fertilization occurred in 45% of the oocytes (n = 1,499). Of 171 treatment cycles, 93% of the couples had fertilization and 86% had ET. Thirty-six pregnancies were achieved. During the period studied, the mean fertilization rate increased from 21.3% during the first 17 weeks to 67.8% during the last 13 weeks, and the pregnancy rate (PR) per started cycle increased from 12.8% to 31.3%. CONCLUSIONS: Technical factors critical for achieving high rates of fertilization and pregnancy were the use of standardized intracytoplasmic sperm injection pipettes, the immobilization of sperm before injection, and the aspiration of a minimal amount of ooplasm before reinjection with the sperm. Intracytoplasmic sperm injection appears to be superior to other micromanipulation methods for alleviating male infertility. PMID- 7890071 TI - Assisted hatching by partial zona dissection of human pre-embryos in patients with recurrent implantation failure after in vitro fertilization. AB - OBJECTIVE: To examine the potential of the partial zona dissection technique to promote successful implantation by assisting embryo hatching after IVF. DESIGN: The study and the control group included 72 and 82 patients, respectively, each had undergone at least three failed IVF-ET attempts. Assisted hatching was performed on four- to six-cell stage embryos by creating a slit in the zona pellucida using the partial zona dissection technique. After 90 minutes incubation (5% CO2, 37 degrees C), the embryos were transferred to the uterus. SETTING: Infertility and IVF Unit of an academic tertiary referral medical center. RESULTS: In the assisted hatching group, 230 micromanipulated embryos were replaced (3 or 4 treated embryos per patient) compared with 295 nonmanipulated embryos in the control group. Clinical pregnancy rates (PRs) were similar in the assisted hatching and control groups (n = 15; 20.8% and n = 12; 14.6%, respectively). However, the contribution of assisted hatching by partial zona dissection to successful implantation was related to the patients's age: patients older than 38 years showed a markedly higher PR after assisted hatching: 23.9% in the study group compared with only 7% of the controls. CONCLUSIONS: These results demonstrate that assisted hatching by partial zona dissection is a quick and efficient method that does not induce any visible damage to the embryos replaced. In a selected group of patients (aged over 38 years, who have failed to conceive in at least three previous IVF attempts) it significantly increases the chances for pregnancy after ET. PMID- 7890072 TI - Randomized trial of partial zona dissection for male infertility. AB - OBJECTIVES: To compare IVF rates using partial zona dissection versus zona intact insemination in couples with male infertility. To analyze pregnancy rates relative to sperm characteristics, fertilization rates, and treatment. DESIGN: Randomized prospective comparison of fertilization in sibling oocytes. Transfer of the three best quality embryos from one or both treatments. SETTING: Department of Gynaecology and Reproductive Medicine, University Hospital, London, Ontario, Canada. PARTICIPANTS: Thirty-two couples undergoing IVF with a principal diagnosis of male infertility. INTERVENTION: Treatment with partial zona dissection. MAIN OUTCOME MEASURES: Fertilization and pregnancy. RESULTS: Fertilization rates were 26% and 9% after partial zona dissection and IVF, respectively. Polyspermy was < 1% in each treatment. There were five singleton pregnancies in 29 completed cycles, three in cycles with fertilization only by partial zona dissection and two in cycles with both partial zona dissection and IVF fertilization. There were no pregnancies after fertilization by IVF only. Stepwise logistic regression analysis indicated that pregnancy was related to partial zona dissection, initial sperm concentration, and total acrosin activity. CONCLUSION: Partial zona dissection was associated with minimal polyspermic fertilization and higher normal fertilization rates than sibling oocytes treated by modified IVF. Pregnancy occurred only after transfer of embryos from partial zona dissection or combined partial zona dissection and IVF. PMID- 7890073 TI - Multiple implantation after oocyte donation: a frequent but inefficient event. AB - OBJECTIVE: To evaluate the natural history of multiple implantation in a donor oocyte program. DESIGN: Retrospective review of clinical pregnancies resulting from donor oocytes with analysis of serial vaginal ultrasound examinations beginning 21 days after embryo transfer. SETTING: University of Southern California IVF program (USC-IVF). MAIN OUTCOME MEASURES: Number of implantation sites lost during gestation, furthest development of the gestation, and clinical symptoms of those experiencing loss. RESULTS: Sixty-two of 101 patients (61%) who became pregnant had multiple implantations, 41 (41%) with two sacs, 12 (12%) with three sacs, 6 (6%) with four sacs, and 3 (3%) with five sacs. Overall 28% of implantations sites were lost spontaneously. Rates of loss were similar for multiple implantations. The majority (62%) of these nonviable sacs did not develop beyond a gestational sac. All patients with three or more implantation sites had ongoing pregnancies through the first trimester. The probability of pregnancy loss after visualization of fetal heart motion was 5.7%. Few patients who underwent a natural self reduction of sacs were symptomatic. CONCLUSIONS: There is a significant self-reduction in multiple implantation sites in a donor oocyte program. This may obviate the need for a selective reduction procedure. Patients should be followed for up to 10 weeks after ET before committing to a selective reductive procedure. PMID- 7890074 TI - Angiotensin-converting enzyme inhibition reverses luteal phase steroid production in oocyte donors. AB - OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibition would affect ovarian steroid synthesis in the oocyte donors undergoing controlled ovarian hyperstimulation (COH). SETTING: The IVF program of the University of Southern California. DESIGN: Prospective matched clinical trial. PATIENTS: Twelve oocyte donors were studied in 28 hyperstimulation cycles. INTERVENTIONS: Donors underwent a standard COH protocol. Follicle aspiration was performed 34 hours after administration of hCG. After the procedure, seven donors were administered the ACE inhibitor, captopril, 6.25 mg orally twice daily for 4 days. The remaining patients served as controls. MAIN OUTCOME MEASURES: Serum E2, P, plasma prorenin, active renin, and angiotensin II (Ang II). RESULTS: Angiotensin II increased after aspiration in both groups but was significantly lower in those receiving captopril. Peak P in the captopril group was significantly lower than controls (81.8 +/- 27.8 versus 208.5 +/- 23.9 ng/mL [conversion factor to SI unit, 3.180]). Peak E2 was significantly higher (2,222.4 +/- 875.3 versus 425.6 +/- 490.4 pg/mL [conversion factor to SI unit, 3.671]). Active renin and Ang II correlated with P. CONCLUSIONS: In stimulated cycles, inhibition of Ang II production appears to raise serum E2 and lower P levels. Angiotensin II, therefore, may have a role in the regulation of ovarian steroid synthesis. PMID- 7890075 TI - Administration of human chorionic gonadotropin for in vitro fertilization-embryo transfer based on the serum luteinizing hormone (LH) concentration: the importance of synchronization with endogenous LH rises. AB - OBJECTIVE: To examine whether synchronized administration of hCG at the onset of the endogenous LH rise promotes successful IVF. DESIGN: A prospective randomized study. SETTING: In vitro fertilization program at a university hospital. PATIENTS: A total of 208 IVF cycles in 148 patients. INTERVENTIONS: Serum LH concentrations were measured daily and hMG was administered daily. Independent of follicle size and E2 concentration, hCG was administered as soon as the LH concentration exceeded the J level, defined as the minimum value + (the day 3 value-the minimum value) x 1/3(J group). Alternatively, hCG was administered when the serum LH concentration turned to increase but was still less than the J level, or 1 day after the serum LH concentration exceeded the J level (non-J group). RESULTS: The rates of total and ongoing pregnancy per cycle were significantly higher in the J group (35.6% and 26.0%, respectively, n = 104) than in the non-J group (21.2% and 12.5%, respectively, n = 104). Pregnancies in the J group were achieved over a wide range of dominant follicle diameters (13 to 25 mm), E2 levels (198 to 1,700 pg/mL; conversion factor to SI units, 3.671), and E2 level per follicle > or = 12 mm (24 to 225 pg/mL per follicle) recorded on the day of hCG administration. CONCLUSION: Synchronized administration of hCG in accordance with endogenous LH rises produces a high rate of pregnancy in IVF. PMID- 7890077 TI - Safety of a freestanding surgical unit for the assisted reproductive technologies. AB - OBJECTIVE: To determine the safety of a freestanding surgical unit for assisted reproductive technology (ART), using the rate of unplanned admissions to a hospital within 24 hours of surgery. DESIGN: Prospective. SETTING: A freestanding surgical unit within a medical office building. PATIENTS: A mixture of private and university-referred patients undergoing 6,776 ART surgical procedures. MAIN OUTCOME MEASURES: Patients admitted during the first 24 hours of surgery were recorded and hospital progress was monitored for invasive procedures, treatments, time of discharge, and residual complications. Variables tabulated included age, fertility diagnosis, ART procedure, E2 level, number of follicles by ultrasound, previous surgery, and type of anesthesia. RESULTS: There were 11 hospital admissions (0.16%). Four patients required surgery: one laparoscopy and three laparotomies. Admissions after vaginal oocyte retrieval were no different from those after GIFT via laparoscopy, 0.16% versus 0.18%, respectively. The number of admissions after monitored anesthesia care was higher than expected compared with general anesthesia. Profiles of hospitalized patients showed no apparent differences from the nonhospitalized patients. CONCLUSIONS: Surgical procedures for ART performed in a freestanding surgical unit can be performed safely with a low hospitalization rate and minimal morbidity. PMID- 7890076 TI - Selective use of leuprolide acetate in women undergoing superovulation with intrauterine insemination results in significant improvement in pregnancy outcome. AB - OBJECTIVE: To examine the incidence of premature luteinization in individuals undergoing hMG with IUI therapy, the association between premature luteinization, cycle fecundity, and pregnancy outcome, and to determine if the selective use of leuprolide acetate (LA) in women demonstrating premature luteinization improves pregnancy outcome in subsequent hMG with IUI cycles. DESIGN AND SETTING: Retrospective analysis of superovulation cycles from January 1990 until December 1991 at the University of Connecticut Health Center. PATIENTS: All women with ovulatory function undergoing hMG superovulation with IUI. INTERVENTIONS: All patients were tested for evidence of premature luteinization. Those demonstrating premature luteinization were started on LA in the luteal phase in their subsequent hMG with IUI cycle. MAIN OUTCOME MEASURES: Peak serum E2, the number of mature preovulatory follicles, the number of ampules of hMG, days of hMG therapy, cycle fecundity, and spontaneous abortion rate. RESULTS: Thirty-three percent of all hMG with IUI patients showed evidence of premature luteinization, with premature luteinization occurring in 22.2% of conception cycles and 37.4% of nonconception cycles. For those women who demonstrated premature luteinization in their conception cycle, 90.0% of the pregnancies ended with either spontaneous abortion or were biochemical in nature compared with 44.3% in the cycles without evidence of premature luteinization. Cycle fecundity was 11.1% in patients demonstrating premature luteinization compared with 26.3% for patients without premature luteinization. All women demonstrating premature luteinization and not conceiving were placed on LA in the luteal phase and had a subsequent cycle fecundity of 18.9% with the percent pregnancy wastage being significantly less (33.3% versus 90.0%) when LA was used. CONCLUSIONS: Premature luteinization is a common occurrence during hMG therapy and is associated with decreased cycle fecundity and an increased incidence of spontaneous abortion and biochemical pregnancies. The selective use of LA in those individuals demonstrating premature luteinization results in a significant increase in the percent of women conceiving a viable pregnancy. PMID- 7890078 TI - The effect of pentoxifylline on sperm motility, oocyte fertilization, embryo quality, and pregnancy outcome in an in vitro fertilization program. AB - OBJECTIVE: To study the effect of pentoxifylline on sperm motility, oocyte fertilization, embryo cleavage, and quality as well as pregnancy outcome on asthenospermic patients participating in an IVF program. DESIGN: Prospective randomized study. SETTING: Private IVF unit. PATIENTS: Ninety-seven couples, 24 of whom were repeating IVF. Two semen specimens were obtained from each patient and each specimen was divided equally into two parts, nontreated (control semen) and pentoxifylline-treated (treated semen). MAIN OUTCOME MEASURE: Sperm progressive motility, oocyte fertilization. RESULTS: Overall and progressive motility did not differ significantly between the two semen specimens. There was a significant increase in the progressive motality of the pentoxifylline-treated semen compared with control semen. No significant difference was noticed between control and treated semen in fertilization rate, cleavage rate, embryo quality, and pregnancy rate. The percentage of patients who fertilized only with control semen (9.3%) was not significantly different from that of patients who fertilized only with treated semen (10.3%). Couples who were repeating IVF did not show significant difference in fertilization between the present study and previous attempts. CONCLUSION: Our results showed that although the sperm progressive motility is improved after pentoxifylline treatment, it is doubtful whether this effect is of any clinical significance. PMID- 7890079 TI - Have sperm counts been reduced 50 percent in 50 years? A statistical model revisited. AB - OBJECTIVE: To reanalyze data that were used in a linear model to predict that mean sperm counts have been reduced globally by approximately 50% in the last 50 years. DESIGN: The mean sperm counts and their temporal distribution were reanalyzed via several different statistical models (quadratic, spline fit, and stairstep). CONCLUSION: There are several reasons why a published linear regression model is inappropriate to infer a 50% reduction in mean sperm counts in the last 50 years. These include [1] the potential selection biases that may have occurred with the 61 assembled studies such that they are not representative of their underlying populations; [2] the likely variability in collection methods, in particular, the lack of adherence to a minimum prescribed abstinence period, as has been stated for the largest study, which contained 29.7% of all the subjects included in the analysis; [3] the paucity of data in the first 30 years of the 50-year trend analysis; [4] the fact that if the last 20 years of data are examined, which contains 78.7% of all the studies and 88.1% of the total number of subjects, there is no decrease in sperm counts, in fact, sperm counts were observed to have increased; [5] the conflicting data from a large individual laboratory, which was not prone to the collection variability that likely occurred between the 61 studies, that did not suggest a decline in mean sperm count or seminal volume during a comparable time period, even though this laboratory published the data that were largely responsible for the high historical values in the linear model; and, most importantly, [6] the variety of other mathematical models that perform statistically better at describing the recent data than the linear model and thus offer substantially different hypotheses. The data are only robust during the last 20 years of the analysis, in which all the models, except the linear model, suggest constant or slightly increasing sperm counts. PMID- 7890080 TI - Flow cytometry provides rapid and highly accurate detection of antisperm antibodies. AB - OBJECTIVE: Immunobead testing (IBT), the current standard for antisperm antibody detection, is time consuming and somewhat subjective. To overcome these limitations and maintain accuracy, we studied an immunofluorescent assay using flow cytometry. DESIGN: A validation study comparing flow cytometry to IBT in the detection of serum antisperm antibodies. SETTING: Flow cytometry laboratory. PATIENTS: Sera from 37 men after vasectomy (test) and sera from 35 fertile men (control). MAIN OUTCOME MEASURE: Test serum with and without immunoglobulin (Ig)G, IgA, and IgM antisperm antibodies as defined by IBT were analyzed by flow cytometry. Sensitivity and specificity of flow cytometry was calculated by defining the IBT as the true result. RESULTS: Flow cytometry identified 22 of 22 sera that were IgG positive (100% sensitivity), 12 of 14 sera that were IgA positive (86% sensitivity), and 4 of 4 sera that were IgM positive (100% sensitivity). Overall, 22 of 37 men were positive for antisperm antibodies. The flow cytometry correctly identified 71 of 71 negative sera (100% specificity). Fluorescence intensity values from the 37 study patients significantly correlated with immunobead binding to the head region and to the entire (more than one) region. CONCLUSIONS: Detection of IgG, IgA, and IgM antisperm antibodies by flow cytometry is highly sensitive and specific. In addition, flow cytometry is able to assess thousands of sperm rapidly and accurately, reducing sampling error and technical time. PMID- 7890081 TI - Effect of age on testicular function in adult males with sickle cell anemia. AB - OBJECTIVES: To determine the effect of age on testicular function and fertility profile of adult males with homozygous sickle cell disease. DESIGN: A comparative cross-sectional study. SETTING: A university teaching hospital in Nigeria. PARTICIPANTS: Twenty-two adult males with homozygous sickle cell disease and 20 healthy adult males with normal hemoglobin genotype. MAIN OUTCOME MEASURES: Seminal indexes, serum concentration of reproductive hormones, body mass index (BMI), testicular volume index, and span-height difference of patients with homozygous sickle cell disease and normal subjects were compared. Also significant differences were sought between two age groups among patients and control subjects: those < or = 25 years old and those > 25 years of age. RESULTS: The mean BMI, testicular volume index, serum T concentration, and indexes of semen quality of the patients with homozygous sickle cell disease were significantly lower than the values for the control subjects. In contrast, there was no significant difference in the mean concentration of FSH, LH, PRL, and mean span-height difference between both groups. Also, although no significant age related effect on serum T concentration, testicular volume index, and sperm density was found in the subjects 18 to 40 years of age with normal hemoglobin genotype, patients > 25 years old with homozygous sickle cell disease had significantly higher mean serum T concentration and mean testicular volume index than those < or = 25 years old; their sperm density was also substantially higher. CONCLUSION: Fertility is impaired in adult males with homozygous sickle cell disease probably as a result of abnormal hypothalamic or pituitary function. There is a significant amelioration of the hypogonadism, abnormal sexual function, and poor semen profile with increasing age. PMID- 7890082 TI - Endometrium preparation with exogenous estradiol and progesterone for the transfer of cryopreserved blastocysts. AB - OBJECTIVE: To determine the implantation rates of cryopreserved blastocysts using controlled E2 and P replacement cycles in women with functioning ovaries. DESIGN: Retrospective clinical study. SETTING: University teaching hospital. PATIENTS: Infertile women with cryopreserved blastocysts obtained from previous IVF attempts. INTERVENTIONS: Exogenous E2 was administered orally from cycle day 1 and P was started transvaginally from day 15. Blastocysts were transferred on the 5th day of endometrial exposure to P (day 19). MAIN OUTCOME MEASURES: Blastocyst implantation rate and pregnancy rate (PR). RESULTS: Ninety-eight percent of blastocysts survived thawing: 67 were transferred in 42 women. Eight pregnancies occurred giving a PR of 19% per ET and 11.9% per blastocyst. CONCLUSION: The high PR observed after transferring blastocysts on the 5th day of endometrial exposure to P in controlled E2 and P replacement cycles speaks for a forward slide of the window of transfer in case of blastocysts. PMID- 7890083 TI - Successful human in vitro fertilization using a modified human tubal fluid medium lacking glucose and phosphate ions. AB - OBJECTIVE: To determine the effect of medium with or without glucose and phosphate on the fertilization and development of human oocytes. DESIGN: Sequential allocation of alternate patients to one of two treatment groups. SETTING: Private practice infertility programs. PATIENTS: Ten couples requesting treatment for infertility. INTERVENTIONS: Gametes from each couple were collected, washed, and incubated in one of two culture media under investigation. MAIN OUTCOME MEASURES: Number of oocytes collected, fertilized, cleaving, replaced, and implanting in each patient. Development of any supernumerary embryos to fully expanded blastocysts in vitro. RESULTS: There was a significant increase in the proportion of transferred embryos implanting in the group of patients whose gametes were handled in medium devoid of glucose and phosphate. All other comparisons of factors that may have influenced implantation rates between the two groups of patients were not significantly different. CONCLUSIONS: High rates of fertilization, cleavage, implantation, and development of supernumerary human embryos to the blastocyst stage in vitro were obtained with a modified human tubal fluid medium containing ethylenediaminetetraacetic acid and glutamine but devoid of glucose and phosphate ions. A prospective randomized trial is necessary to evaluate the clinical significance of these observations. PMID- 7890085 TI - Interleukin-8 concentrations are elevated in peritoneal fluid of women with endometriosis. AB - OBJECTIVE: To investigate the presence of interleukin-8 (IL-8), a macrophage derived angiogenic factor, in peritoneal fluid (PF) of women with and without endometriosis. DESIGN: Case-control study. SETTING: University hospital. PATIENTS: Eighteen women with laparoscopic findings of mild to severe endometriosis, and nine women with no visual evidence of pelvic pathology. MAIN OUTCOME MEASURES: Peritoneal fluid IL-8 levels were determined using an ELISA. Interleukin-8 concentrations were compared among women with and without endometriosis. Correlation between PF IL-8 concentration and endometriosis stage was investigated. RESULTS: Interleukin-8 was detectable in the PF of a majority of women (67%). Interleukin-8 concentrations were higher in the PF of women with endometriosis than in matched normal controls. A significant correlation between PF IL-8 concentration and endometriosis stage was noted. CONCLUSIONS: We hypothesize that IL-8 is an important angiogenic factor that contributes to the pathogenesis of endometriosis by promoting the neovascularization of ectopic endometrial implants. PMID- 7890084 TI - A simple method for preparing modified TES and Tris yolk buffer that is optically clear and membrane filterable. AB - OBJECTIVES: To determine whether modified TES and Tris (TEST) yolk buffer (TYB) made using a commercially available egg yolk extract would exhibit lab performance characteristics equal to the existing preparation made with whole egg yolk and to define the phospholipid content of the new modified TYB formulation. DESIGN: Divided ejaculates from 21 normozoospermic and 7 oligozoospermic males presenting for pre-IVF evaluation were stored at 0 to 4 degrees C for 42 hours using commercially available or modified TYB before analysis in the optimized sperm penetration assay (SPA). SETTING: A commercial tissue culture manufacturer and a clinical fertility reference laboratory. MAIN OUTCOME MEASURES: Sperm swim up recoveries and average penetrations per ovum, determined by the SPA, were used as measures of sperm function. High-pressure liquid chromatography (HPLC) was used to profile the egg yolk extract. RESULTS: No significant differences in either sperm swim-up recovery rates or SPA results were found in normal or poor quality semen that was treated with modified or commercial TYB. The major constituent in commercial egg yolk extract is lecithin. CONCLUSIONS: Commercially available egg yolk extract passes easily through a 0.2-microns filter, is a rich source of lecithin, and can be substituted effectively for whole egg yolk in preparing TYB. PMID- 7890086 TI - Does an oil-based contrast media enhance fertility? PMID- 7890087 TI - Unaudited clinical experience. PMID- 7890088 TI - Unaudited clinical experience. PMID- 7890089 TI - Unaudited clinical experience. PMID- 7890090 TI - Value of sperm morphology. PMID- 7890091 TI - The nature of gender. AB - I explain a biosocial model of women's gendered behavior (behavior on which the sexes differ). This model integrates a macro sociological theory with a biological theory derived from primate behavior. The sociological model is designed to explain changes in the relationship between sex and behavior over time or between groups. The biological model is designed to explain individual within-sex variance and between-sex variance in gendered behavior in a cohort. Results from an original study are presented to demonstrate that within-sex variance in women's gendered behavior is explained well by the primate model. I conclude that human nature is gendered. The implications of this conclusion are explored for demographic and other social science research. PMID- 7890092 TI - Family structure, residential mobility, and school dropout: a research note. AB - This paper examines the hypothesis that high levels of residential mobility among nonintact families account for part of the well-known association between living in a nonintact family and dropping out of high school. Children from single parent families and stepfamilies are more likely than children from two-parent families to move during the school year. As much as 30% of the difference in the risk of dropping out between children from stepfamilies and children from intact families can be explained by differences in residential mobility. Previously, mechanisms explaining school failure on the part of children in nonintact families were more plausible for children in single-parent families than for children in stepfamilies; high levels of residential mobility apply to both groups of children. In addition, residential mobility lends itself to manipulation by public policy, with potentially remedial effects for vulnerable children. PMID- 7890093 TI - A sensitivity analysis of repeat migration attrition in the study of migrant adjustment: the case of Bangkok. AB - Studies of migrant adjustment often conclude that results apply only to remaining migrants. This paper examines the potential bias in using the difference between remaining migrants and natives as a measure of migrant adjustment. The results document that differences between remaining migrants and natives contain bias caused by attrition due to repeat migration. Such bias is small, however, and is unlikely to change migrant-native comparisons. Unless one is concerned with details of differences between migrants and natives, it is unnecessary to be concerned about migration attrition bias in drawing conclusions from the observed differences. PMID- 7890095 TI - Neighborhood context and the transition to sexual activity among young black women. AB - Previous studies report that neighborhood characteristics influence pregnancy and childbearing risk among African-American adolescent women. These studies, however, leave unidentified the effects of many neighborhood properties on the proximate determinants of nonmarital fertility. In this study I examine the effects of neighborhood characteristics on the risk of nonmarital first intercourse and on contraceptive use among black female adolescents. The results suggest that neighborhood socioeconomic status, female employment and marital dissolution rates, and peers' departure from mainstream lifecourse trajectories influence young black women's sexual and contraceptive behavior. The effects of female employment and socioeconomic status are greater for teens in urban neighborhoods than for teens living elsewhere. PMID- 7890094 TI - Employment and the use of birth control by sexually active single Hispanic, black, and white women. AB - Previous studies of the use of birth control by sexually active single women tend to emphasize family background and aspirations, and restrict their attention to teenagers. We elaborate this framework by considering how labor market experiences might shape the birth control practices of women in their late teens and twenties. Data from the National Longitudinal Survey of Labor Force Experiences--Youth Cohort provide evidence that employment histories and wages influence birth control practices, net of the effects of family background, aspirations, and educational attainment. Several pronounced racial and ethnic differences are found. PMID- 7890096 TI - The persistence of high fertility in the American South on the eve of the baby boom. AB - Pockets of high fertility persisted in some areas of the American South through the Great Depression. Most other areas of the country adopted modern fertility patterns considerably earlier in the century; these "laggard" areas are clear exceptions to the national demographic revolution in family building. In this paper we attempt to identify the factors that account for the persistently high fertility in some southern regions. We use county-level data for 1940 to assess the utility of three theoretical models of fertility: structural, diffusion innovation, and health. Differences by race are also considered, in view of the distinctly different histories of whites and African-Americans in the south. Our findings suggest that unicausal explanations for the persistence of high fertility are too simplistic; all three theoretical perspectives receive empirical support. Considerable similarity is observed in the findings for blacks and for whites. Yet important differences also emerge, especially the more powerful effects of structural variables on white fertility. We conclude that the evidence indicates the need for "diversity" in the study of demographic behavior. Not only should we examine a variety of causal mechanisms for demographic phenomena; we also should consider the varying utility of those mechanisms across different social groups. PMID- 7890097 TI - Age patterns of mortality and cause-of-death structures in Sweden, Japan, and the United States. AB - This paper uses a new standard model of adult mortality to compare the mortality patterns of Swedes, Japanese, and U.S. whites between 1950 and 1985. It examines changes in the age patterns of mortality and the cause-of-death structures within the populations, and the relationships between those two factors. As Japan has reached a level of mortality similar to that in Sweden, the age patterns of mortality in the two populations have become more similar despite distinct differences in causes of death. The United States has a cause-of-death structure similar to that of Sweden, but the age pattern of mortality is very different. High mortality in the middle age range in the United States results in approximately a one-year loss of life expectancy at age 45 in comparison with Sweden. PMID- 7890098 TI - The impact of child care on fertility in urban Thailand. AB - Women's labor force participation in Thailand, particularly in the modern sector, recently has increased in conjunction with rapid declines in fertility. This paper examines whether a relationship exists between child care considerations and fertility decision making among Bangkok women. Although the two-child family has become the norm in recent years, and although most respondents said that ideally they would like to have two children, a high proportion of women surveyed said they planned to only have one child. Women's work status and type of employment is found to strongly affect the likelihood of having a second birth: those who work at jobs that not only are low-paying but are located in a formal setting are least likely to have a second child. The type of child care for the first child also has an impact: those whose first child is in a less preferred situation are less likely to have a second. Variables measuring the need for and type of child care are found to have greater consequences for fertility than do usual measures of socioeconomic status. PMID- 7890099 TI - Cause, incidence, and prevention of trauma to teeth. AB - The cause, incidence, and prevention of trauma to teeth are highlighted from a contemporary aspect. Causative factors have become more diverse, and the incidence of trauma has become almost equal in both sexes. Newer areas identified include domestic violence, enhanced sporting activities, and an increase in adverse societal manifestations. Prevention, with a focus on education and awareness of diverse populations, is discussed. PMID- 7890100 TI - Clinical management of injuries to the maxilla, mandible, and alveolus. AB - Facial bone and especially mandibular fractures are injuries in which first aid and management of late complications require dental professionals, and consequently all dentists should be familiar with the modern principles of their treatment. Tooth involvement is common in mandibular and maxillary fractures and can require more treatment than does the jaw fracture. Nonsurgical treatment of bone fractures involves immobilization, which for the facial bones is achieved with maxillomandibular fixation (MMF) using dental fixed arch bars. Hence, associated tooth injuries are difficult or impossible to treat during immobilization, so that some treatment is necessary beforehand (for example, coverage of exposed dental areas, temporary filling of crown fractures, repositioning of luxated teeth, and endodontic treatment if the pulpal vascular supply is lost in the accident). Operative treatment of mandibular and/or maxillary fractures nevertheless involves some disadvantages and risks of complications. Teeth on the line of a mandibular fracture should not be extracted as a first-aid measure unless they impair repositioning of the jaw fragments. MMF can be avoided by means of direct internal fixation, which in principle allows treatment of associated dental injuries. PMID- 7890101 TI - Management of trauma to primary and developing teeth. AB - Traumatic dental injuries to the young child can present both diagnostic and therapeutic challenges. Luxation injuries to the primary dentition are the most common injuries. Yet, they are the most controversial with regard to definitive treatment, prognosis, and sequelae. Damage to the developing teeth subsequent to primary tooth injury is often unavoidable and has permanent effects on the dentition. Diagnostic criteria, treatment options, and outcomes are presented in this article; however, treatment decisions are often based on patient behavior. PMID- 7890102 TI - Evaluation, diagnosis, and treatment of the traumatized patient. AB - This article discusses the early assessment of the patient who has sustained an oral injury. The various types of orofacial injuries are reviewed, with emphasis on their early management. The dentist's early assessment of the patient must include a general evaluation of the patient as well as a more specific dental evaluation because the general dentist is often the first person to assess a patient who has been injured. PMID- 7890103 TI - Periodontal management and root extrusion of traumatized teeth. AB - Traumatically induced coronal fractures frequently extend below the free gingival margin. Diagnostic criteria are presented to differentiate those for which crown lengthening alone is appropriate from those that also require orthodontic extrusion. A simplified crown-lengthening technique is described for the exposure of a fracture margin. PMID- 7890104 TI - Aesthetic management of traumatized anterior teeth. AB - The emergency of a traumatically injured tooth occurs frequently in a general dental practice. Patients, staff, and dentist should know what restorative techniques are available to manage the crisis. When the emergency occurs, the patient is probably going to call the dental office. The staff must be prepared for triage of the emergency so that the dentist can plan on the best course of action to manage the clinical circumstance. One method of triaging an emergency caused by traumatic injury to the tooth is by using a short questionnaire that can be completed either by the office staff member taking the telephone call or by the patient if present. This can provide important information for the treatment of the situation. Clinically, the traumatized anterior tooth needs immediate attention. The pulpal status of the tooth needs to be assessed and in the case of tooth or restoration fracture, the circumstances many times dictate an immediate restorative treatment to correct an unaesthetic situation. This article provides the dentist and staff with a variety of restorative techniques that address the aesthetic management of anterior teeth that have been traumatized. PMID- 7890105 TI - Legal considerations for treatment following trauma to teeth. AB - When treating an orally traumatized patient, the dentist has no fewer professional and legal responsibilities than when treating a nonemergency patient. After obtaining proper consent, the examination, diagnosis, treatment, and follow-up of the patient must not be made negligently. Minimally, the dentist must not practice below the standard of care of a similar practitioner acting in the same or similar circumstances. The dentist also may be called on to further assist that patient in his or her attempt to obtain compensation for loss brought about by the trauma. PMID- 7890106 TI - Treatment of the avulsed permanent tooth. Recommended Guidelines of the American Association of Endodontists. PMID- 7890107 TI - Clinical management of crown fractures. AB - Contemporary treatment of uncomplicated and complicated crown fractures is presented in this article. New concepts and approaches are discussed in relation to modern research and new restorative materials. Practical suggestions for the recognition and clinical management of various types of crown fractures are described. PMID- 7890108 TI - Clinical management of transverse root fractures. AB - Successful management of a tooth that has sustained a transverse root fracture depends on three major factors: the position of the fracture line, the extent of mobility of the coronal segment, and the state of the pulpal tissue. The position of the fracture line and its relationship to the base of the gingival crevice are the most important factors in determining the long-term prognosis for the tooth. PMID- 7890109 TI - Luxation injuries. AB - Luxation injuries range in severity from a mild blow to a more severe form, which can cause pulpal necrosis and additional sequelae. This article reviews the epidemiology and describes the various classifications, the appropriate treatment, and the various sequelae of luxation injuries. PMID- 7890110 TI - Clinical management of the avulsed tooth. AB - Treatment outside the dental office: Replant immediately after gentle washing if practical. If replantation is not practical, store the tooth in the best medium available. Storage media in order of preference are Hank's Balanced Salt Solution (HBSS), milk, saline, and saliva (buccal vestibule). Water is the least desirable storage medium. Treatment in the office: Emergency visit; Place tooth in HBSS while exam is conducted and history is taken. Prepare socket for gentle repositioning of the tooth. Prepare the root. Extraoral dry time < 20 minutes: Closed apex--replant immediately after gentle washing. Open apex--soak in 1 mg doxycycline in 20 mg saline for 5 minutes. Extraoral dry time 20 to 60 minutes: Soak in HBSS for 30 minutes and replant. Extraoral dry time > 60 minutes: soak in citric acid, 2% stannous fluoride, and doxycycline and replant. Endodontics can be done extraorally. Semirigid splint for 7 to 10 days. (If alveolar fracture is present, rigid splint for 4 to 8 weeks). Suture soft-tissue lacerations, particularly in the cervical area. Administer systemic antibiotics (penicillin V potassium if possible) Chlorhexidine rinses and stringent oral hygiene while the splint is in place (7 to 10 days). Analgesics as required. Second visit after 7 to 10 days: Endodontic treatment: Tooth with open apex and extraoral dry time of < 60 minutes: No endodontic treatment initially. Recall every 3 to 4 weeks to examine for evidence of pathosis. If pathosis is noted, disinfect the pulp space and start apexification procedure. Tooth with open apex and extraoral dry time > 60 minutes: If endodontics was not completed in the emergency visit, start endodontics and follow apexification procedure. Tooth with closed apex: Endodontics should be initiated after 7 to 10 days. Careful chemomechanical instrumentation under strict asepsis. Splint removed at end of visit. Obturation visit: If endodontics was initiated 7 to 10 days after the avulsion, obturation can take place after short-term calcium hydroxide treatment. If endodontics was initiated more than 14 days after the avulsion or inflammatory resorption, long term calcium hydroxide for 6 to 24 months, obturated when an intact lamina dura is traced. Restorations: Temporary restorations: Should be 4 mm deep. Reinforced zinc-oxide-eugenol, acid-etch composite resin, glass-ionomer cement. Permanent restoration: Placed immediately after obturation. Acid-etch resin and dentin bonding agents. Follow-up care: Twice per year for 3 years and yearly for as long as possible. Late complications are common. PMID- 7890111 TI - E1/E2 type cation transport ATPases: evidence for transient associations between protomers. AB - E1/E2 type cation transport ATPases are known to exist in different conformeric states. Recent evidence characterizing these conformers in membrane is reviewed. A consensus view is proposed in which E2 conformers tend to form oligomeric complexes by lateral association between monomeric protomers and E1 conformers exhibit the opposite behaviour. It is suggested that transient associations between monomers during cation pump cycles may be a common feature of the ion translocation mechanism under physiological conditions. PMID- 7890112 TI - Induction of cytochrome P450 by toluene. AB - At least six cytochrome P450 (P450) isoenzymes, including CYP1A1/2, CYP2A1, CYP2B1/2, CYP2C6, CYP2C11 and CYP2E1, are involved in the metabolism of toluene in rat liver. Toluene exposure induces CYP1A1/2, CYP2B1/2, CYP2E1 and CYP3A1, but decreases CYP2C11/6 and CYP2A1 in adult males. Both sex and age influence the induction of P450s by toluene: in general, the inductive effect is more prominent in younger than in older animals; in males than in females. Neonatal exposure to toluene causes significant changes in liver microsomal P450 dependent monooxygenase activities during the early stage of life, whereas the effects on the rats of more than 3 weeks of age are small. Although structurally related chemicals of toluene also influence similar hepatic P450 isoenzymes, the degree of CYP2B1/2 induction increases, whilst that of CYP2E1 decreases with increasing molecular weight and aliphatic moieties. Unlike liver, exposure to toluene does not influence the distribution of pulmonary or renal microsomal P450-related enzyme activity in rats. In humans, occupational exposure to toluene is so low that it could not lead to the induction of P450. However, the induction may be seen in toluene sniffers who are exposed to high concentrations. PMID- 7890113 TI - Interactions of adriamycin aglycones with mitochondria may mediate adriamycin cardiotoxicity. AB - Adriamycin and related anthracyclines are potent oncolytic agents, the clinical utility of which is limited by severe cardiotoxicity. Aglycone metabolites of Adriamycin (5-20 microM) induce a Ca(2+)-dependent increase in the permeability of the inner mitochondrial membrane of both heart and liver mitochondria to small (< 1,500 Da) solutes; this phenomenon is accompanied by release of mitochondrial Ca2+, mitochondrial swelling, collapse of the membrane potential, oxidation of mitochondrial pyridine nucleotides [NAD(P)H], uncoupling, and a transition from the condensed to the orthodox conformation and is inhibited by ATP, dithiothreitol, the immunosuppressant cyclosporin A, and the ubiquitous polyamine spermine. Aglycones also modify mitochondrial sulfhydryl groups and induce a Ca2+ independent oxidation of mitochondrial NAD(P)H which appears to reflect electron transport from NADH to oxygen, mediated by the aglycones and resulting in the production of superoxide (O2-). Selenium deficiency and butylated hydroxytoluene inhibit aglycone-induced Ca2+ release from liver, but not heart, mitochondria, suggesting that the interactions of the aglycones with mitochondria differ in these two tissues. It can be proposed that the effects of Adriamycin aglycones on heart mitochondria are responsible for the cardiotoxicity of the parent drug. PMID- 7890114 TI - Mechanisms of initiating calcification. ATP-stimulated Ca- and Pi-depositing activity of isolated matrix vesicles. PMID- 7890115 TI - Selective inactivation of muscarinic receptor subtypes. AB - Muscarinic receptors exist in multiple subtypes, denoted as M1, M2, M3 and M4, encoded by four distinct but related genes. A fifth gene product, m5, has also been predicted although this sequence awaits a pharmacological equivalent. Many tissues express more than one muscarinic receptor subtype, which may couple to different intracellular effectors and thus have different physiological roles. One way to characterize the role of each receptor is to selectively inactivate one receptor population, thus pharmacologically 'isolating' the muscarinic receptor subtype of interest. Selective receptor inactivation can be achieved using either a selective, irreversible antagonist, or protection using a selective, reversible antagonist against a non-selective irreversible antagonist. Therefore, combination of these two approaches may provide optimal selective inactivation. Several muscarinic alkylating agents have been identified, including phenoxybenzamine, EEDQ (N-Ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) and propylbenzilylcholine mustard. These irreversible antagonists do not, in general, discriminate between muscarinic receptor subtypes and are frequently used to estimate the affinity and relative efficacy of muscarinic agonists. Consequently, use of these irreversible antagonists provides estimations of the 'receptor reserve' associated with a response mediated by muscarinic receptor activation. In contrast, 4-DAMP mustard (4-diphenylacetoxy-N-(2 chloroethyl)piperidine) selectively inactivates M3 receptors, but will not discriminate between M1, M2 or M4 receptors. In the absence of highly selective alkylating agents, receptor protection by reversible antagonists may be used. Thus, reversible antagonists, such as pirenzepine, methoctramine or para fluorohexahydrosiladifenidol, at appropriate fractional receptor occupancies, may protect M1, M2 or M3 receptors against alkylation by phenoxybenzamine. Selective alkylation of M3 receptors by 4-DAMP mustard is enhanced with concurrent M2 protection. This approach has been applied to defining the role of these muscarinic receptor subtypes in the control of ileal smooth muscle tone. These data suggest that, in ileum, M2 receptors may act to inhibit beta-adrenoceptor activation, thereby offsetting relaxation, while M3 receptors directly mediate contraction. PMID- 7890117 TI - Inhibition of porphobilinogenase by porphyrins in Saccharomyces cerevisiae. AB - The biosynthesis of uroporphyrinogen III, the precursor of hemes, chlorophylls, corrins and related structures, is catalyzed by the porphobilinogenase system (PBGase), a complex of two enzymes, PBG-Deaminase (PBG-D) and Isomerase. Although the separate enzymes have been studied in some detail less work has been performed on the properties of the complex. In this study the kinetic behaviour of the enzyme PBGase in a normal yeast strain, D273-10B, and its derivative B231 has been investigated. Uroporphyrinogen formation was linear with time up to 2 hr at 37 degrees C. The enzyme complex shows classical Michaelis-Menten kinetics. From the double reciprocal plots kinetic parameters were estimated for PBGase and PBG-D. Porphyrins were found to be competitive inhibitors with respect to porphobilinogen (PBG) and these compounds appeared to act as inhibitors by forming dead-end complexes with the free enzyme. 5-Aminolevulinic acid (ALA) also inhibited PBGase and this inhibition was overcome by addition of levulinic acid (2 microM). These results indicate that ALA, is not an inhibitor but acts through its conversion into porphyrins which are the true inhibitors. PMID- 7890116 TI - Partial purification and further characterization of the novel endoglucosaminidase from human serum that hydrolyses 4-methylumbelliferyl-N acetyl-beta-D-chitotetraoside (MU-TACT hydrolase). AB - A novel endoglucosaminidase, originally described by Den Tandt et al. [Int. J. Biochem. 20 (1988), 713-719] and bearing the provisional name MU-TACT hydrolase, was purified from human serum 56,000-fold by means of ammonium sulphate precipitation, anion-exchange chromatography, Con A-Sepharose chromatography and gel filtration on Sepharose CL-6B followed by Superose 12 HR. Based on the latter technique the native apparent molecular weight of the enzyme appeared to be equal to that of myoglobin, being approx. 17 kD. The enzyme eluted clearly at a different volume than lysozyme. MU-TACT is a commercially available substrate for lysozyme. For unknown reasons two major peptides co-purify that give bands on SDS PAGE of 55-60 and 31 kD, respectively. PMID- 7890118 TI - Calmodulin and cAMP dependent synaptic vesicle protein phosphorylation in rat cortex following lead exposure. AB - The effect of in vivo and in vitro lead exposure on calmodulin and cAMP dependent synaptic vesicle protein phosphorylation has been investigated. Lead could enhance calmodulin activity following in vitro and in vivo lead exposure. The calmodulin dependent synaptic vesicle protein phosphorylation was enhanced following in vivo and in vitro lead exposure resulting in the depletion of the neurotransmitters norepinephrine and acetylcholine. The cAMP dependent synaptic vesicle protein phosphorylation was inhibited by both in vitro and in vivo lead treatment. The results suggest that lead adversely affects synaptic vesicle protein phosphorylation and this may ultimately effect synaptic functions. PMID- 7890119 TI - Two nuclear-coded subunits of mitochondrial complex I are similar to different domains of a bacterial formate hydrogenlyase subunit. AB - A computer comparison of protein sequences revealed similarity between the 30.4 kDa subunit of complex I from the fungus Neurospora crassa and the ORF5 subunit of formate hydrogenlyase from Escherichia coli. The ORF5 protein was previously known to be homologous to the 49 kDa component of the mitochondrial enzyme. We show that the 30.4 kDa corresponds to the N-terminal part while the 49 kDa subunit corresponds to the C-terminal portion of the bacterial protein. Thus, this bacterial protein represents a fusion of the two mitochondrial polypeptides suggesting that the two complex I genes arose from a single ancestor. Our results indicate that the 30.4 kDa and 49 kDa subunits are part of a structural and functional unit in complex I. PMID- 7890120 TI - Characterization of human arylsulfatase A glycans. AB - Despite numerous studies on arylsulfatase A, the structure of the glycans present in each of its two subunits has not been determined. This is important because the carbohydrate component of human arylsulfatase A synthesized in tumor tissues and transformed cells has been shown to undergo apparent changes. This study elucidates some of their major features. Glycan chain analysis of native and deglycosylated arylsulfatase A as well as its subunits was performed with the use of a Glycan Differentiation Kit and lectin affinity chromatography. Each of the two subunits of arylsulfatase A from placenta, separated electrophoretically on polyacrylamide gel in reducing conditions, reacted with digoxigenin-labelled Galantus nivalis agglutinin and Aleuria aurantia agglutinin, while those from liver enzyme reacted with the former only. The subunits of both enzymes did not react with Sambucus nigra, Maakia amuriensis, Datura stramonium or Peanut agglutinin. Deglycosylation of arylsulfatase A with peptide N-glycosidase F and endo-beta-N-acetylglucosaminidase F resulted in complete cleavage of its carbohydrate component from each subunit. Their molecular weights decreased by 3 kDa. Neuraminidase treatment of the enzyme from liver and placenta followed by isoelectrofocusing separation showed the presence of sialylated forms which constituted a small percentage of total enzyme activity. Placental arylsulfatase A became bound to Lens culinaris agglutinin agarose, while no interaction with Ricinus communis or Griffonia simplicifolia agglutinin agarose was observed. The study shows that both subunits of arylsulfatase A from human placenta possess two high mannose/hybrid type glycans as major structures, with at least one 6-O-L fucose bound to the innermost N-acetylglucosamine on each.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7890121 TI - The 5'-sequence of the murine Hox-b3 (Hox-2.7) gene and its intron contain multiple transcription-regulatory elements. AB - We sought to clone and characterize the murine Hox-b3 gene. In Xenopus embryos, the homologous gene has been shown to be responsive to retinoic acid, an agent which has profound effects on tissue growth and development. By plaque hybridization, using a partial, murine Hox-b3 cDNA as a probe, we screened a genomic library and isolated a series of overlapping clones. Restriction fragments from positive clones were sequenced by the dideoxy method on an automated DNA sequencer. We report the genomic sequence of the murine Hox-b3 gene. The sequence has been submitted to the GenBank database (accession number U02278). Our sequence extends from the P1 promoter through the coding sequence of the gene to the 3'-untranslated region. In common with other homeobox genes, there is an intron between the conserved hexapeptide and the homeobox. It is 866 bp long and has 3'- and 5'-splice sites very similar to the consensus, a long polypyrimidine tract and a potential branch point near the 3'-splice site. We have analyzed the sequence 5' to the initiation codon and the intron for putative control elements, and have identified a series of putative transcription factor binding sites in the P1 promoter and intron, including two for the retinoid X receptor-beta. Their possible significance is discussed. The sequences we have identified may be responsible for the observed pattern of expression of the gene. This sequence and the clones from which it is derived will enable a molecular dissection of the P1 promoter region. PMID- 7890122 TI - Biochemical characterization of hemorrhagic toxin from Crotalus viridis viridis (prairie rattlesnake) venom. AB - Hemorrhage, necrosis and edema are some of the effects often observed following snake bites. This paper reports studies on the isolation and biological properties of hemorrhagic toxin from Crotalus viridis viridis (Prairie rattlesnake) venom. A hemorrhagic toxin was isolated from C. v. viridis venom by Sephadex G-50, DEAE-Sephacel and Q-Sepharose column chromatographies. The hemorrhagic toxin from C. v. viridis venom was shown to be homogenous as demonstrated by a single band on polyacrylamide gel electrophoresis and immunodiffusion. Its molecular weight was approximately 54,000 daltons, and it contained 471 amino acid residues. The toxin possessed hemorrhagic activity with a minimum hemorrhagic dose (MHD) of 0.11 micrograms and hydrolytic activity on dimethylcasein, casein, azocasein, azoalbumin, azocoll and hide powder azure. Hemorrhagic and casein hydrolytic activities were inhibited by EDTA, o phenanthroline or dithiothreitol. The toxin contained 1 mole of zinc per mole of protein and zinc is essential for both hemorrhagic and proteolytic activities. Hemorrhagic toxin possessed hydrolytic activity on the B-chain of insulin, which cleaves His(5)-Leu(6), His(10)-Leu(11), Ala(14)-Leu(15), Tyr(16)-Leu(17) and Phe(24)-Phe(25) bonds. This toxin also hydrolyzed A alpha and B beta chains of fibrinogen. Intramuscular injections of hemorrhagic toxin caused an increase of creatine phosphokinase activity in mice serum from 50.3 mU/ml to 1133 mU/ml. A toxin isolated from C. v. viridis venom was shown to have strong hemorrhagic activity. Partial characterization is reported for this major hemorrhagic toxin in C. v. viridis venom. PMID- 7890123 TI - Food for thought. PMID- 7890124 TI - Bilateral spastic cerebral palsy--a collaborative study between southwest Germany and western Sweden. III: Aetiology. AB - In this third report from the collaborative study of children with bilateral spastic cerebral palsy born between 1975 and 1986, aetiology was analysed. Evidence for a prenatal aetiology increased with gestational age, whereas evidence for a peri-/neonatal aetiology decreased. The largest subgroup, the leg dominated subtype, showed the same distribution of aetiology as the total group. A prenatal aetiology was found mainly among term and moderately preterm children with a four-limb-dominated subtype; a peri-/neonatal aetiology among very preterm children with a three- or four-limb-dominated subtype or among term children with a dyskinetic-spastic subtype. The findings support the hypothesis generated from the authors' epidemiological results of a peri-/neonatal aetiology being predominant among preterm, and a prenatal aetiology among term, children with bilateral spastic cerebral palsy. PMID- 7890125 TI - Neonatal stroke involving the middle cerebral artery in term infants: clinical presentation, EEG and imaging studies, and outcome. AB - Six children with neonatal cerebral infarction of the middle cerebral artery are reported. Seizures or respiratory distress were the initial symptoms. In some cases abnormal findings appeared earlier on EEG than on ultrasound. The EEG changes were concordant with the localization of the lesion. Ultrasound examinations revealed an echodense structure within the vascular territory, after a phase of appearing to be normal, highly suggestive of cerebral infarction. The diagnosis was confirmed by CT scan. Findings on EEG, cranial ultrasound and CT suggested that the stroke represented a late intra-uterine event. At long-term follow-up, six children had failed to develop normally for age and had become obviously hemiplegic as gross motor development proceeded. Four of the patients had developed epilepsy. These data indicate that the outcome of neonatal stroke may not be as positive as previously reported. PMID- 7890126 TI - 18-Fluorodeoxyglucose positron emission tomography in children and adolescents with traumatic brain injury. AB - Twenty-two previously normal children and adolescents who suffered a severe, non penetrating traumatic brain injury had PET during rehabilitation at a median of 1.5 months after the injury. Outcome was assessed at a median of 25 months after brain injury. 16 subjects had CT or MRI within 24 days of PET and 11 subjects had a second PET at the point of outcome (median 28 months after first PET). The PET score (obtained by adding the score of 15 brain regions: normal metabolism = 1; reduced = 0) was significantly associated with the clinical outcome measure. PET earlier than 12 weeks after head trauma correlated with outcome, but later PET did not. PET scores improved significantly between rehabilitation and outcome for the 11 subjects who had two PETs, but improvement was not associated with improvement in clinical condition. PET score did not add to the amount of variance explained in the last regression model for prediction of outcome when the results of contemporaneous CT/MRI and clinical condition were taken into account. The data suggest that routine PET during rehabilitation is no more useful than contemporaneous CT or MRI for prediction of outcome. PMID- 7890127 TI - Outcome at three years of sick neonates involved in a double-blind trial of two parenteral amino acid preparations. AB - The authors investigated the hypothesis that neonates who received a parenteral amino acid preparation causing high plasma amino acid levels in the first week of life would perform less well at follow-up than those who received a preparation in which the plasma aminogram fell persistently within the normal range. 27 surviving children who had received either preparation as neonates underwent psychometric assessment at three years. Parents completed three questionnaires about temperament, behaviour screening and socio-economic status. Four of 10 patients who had received one preparation and two of 17 infants who had received the other were of below-average intelligence. This may be related to the different amino acids in the mixtures and the hyperamino-acidaemia caused by this. PMID- 7890128 TI - Convulsive status epilepticus in children treated for epilepsy: an assessment of management. AB - The acute care and further management plans accorded to eight children, all already on treatment for epilepsy, admitted to hospital with a total of 17 episodes of convulsive status epilepticus were examined. Emergency treatment was appropriate, but longer-term management tended to be less than adequate. The causes of status epilepticus were not considered before discharge on 10 occasions. Advice on simple preventative measures was rarely given to the parents. Junior staff require further training in these areas. PMID- 7890129 TI - Decreasing perinatal mortality: unchanged infantile spasm morbidity. AB - The present study examined whether changes in the incidence of infantile spasms could be used to evaluate changes in the quality of pre- and perinatal care over time. 107 children in 1960 to 1976, and 102 in 1977 to 1991, developed infantile spasms in southern Finland. The number of small-for-gestational age (SGA) infants and infants with neonatal hypoglycaemia decreased significantly. Brain malformations, malformation syndromes and patients with tuberous sclerosis increased; this probably reflects the development of more refined neuroradiological screening methods. SGA infants are probably more apt to develop infantile spasms than preterm infants appropriate for gestational age. Early prenatal factors seem to play a major role in the genesis of infantile spasms. Little can be done to reduce the incidence of infantile spasms, but every effort should be made to reduce the number of SGA infants by good prenatal care. Treatment of hypoglycaemia is important because infantile spasms might be preventable in these infants. PMID- 7890130 TI - Endogenous opioids and opiate antagonists in autism: brief review of empirical findings and implications for clinicians. AB - Endogenous opioid dysfunction hypotheses for the development of autism are reviewed, along with clinical empirical studies of opiate antagonists in autism and self-injurious behaviour. There is not yet sufficient evidence to suggest the use of opiate antagonists in the treatment of autism. Further research, particularly of natrexone in severe self-injury, is warranted. PMID- 7890131 TI - Deletion status and intellectual impairment in Duchenne muscular dystrophy. AB - The authors collected Verbal, Performance and Full-scale IQs for 74 patients in whom complete analysis of the dystrophin gene for deletions and duplications had been performed. There was a significant difference in the mean Full-scale IQ between patients with deletions at the 5' and 3' ends of the gene, with no patients with 5' deletions having mental retardation. No relationship was established between mental retardation and the presence or absence of deletions or length of deletions, and similar deletions were observed in the presence and absence of mental retardation. Although distal deletions were more commonly associated with mental retardation, there was no clear evidence for a particular region of the dystrophin gene being specifically responsible for IQ. The intellectual deficit seen in DMD may be a consequence of cerebral hypoxia, ue to malfunction of smooth muscle dystrophin. PMID- 7890132 TI - Sydenham's chorea: a case showing reversible striatal abnormalities on CT and MRI. AB - Sydenham's chorea has not previously been associated with abnormal findings on CT scan, but there have been reports of abnormal MRI in affected patients. The authors describe a case of Sydenham's chorea in which striatal abnormalities were found on both CT and MRI. Repeat MRI when the patient's illness had resolved was virtually normal. This suggests that abnormal imaging is entirely compatible with a diagnosis of Sydenham's chorea in a patient with an appropriate clinical history. Resolution of such abnormalities on repeat scanning provides further support for the diagnosis. PMID- 7890133 TI - Infant botulism--is it that rare? PMID- 7890134 TI - Melatonin treatment of chronic sleep disorders. PMID- 7890135 TI - Are continuous spike-wave discharges during slow sleep (CSWSS) an iatrogenic condition? PMID- 7890136 TI - Inability of children with cerebral palsy to walk at six years. PMID- 7890137 TI - Comparative analysis of the tissue distribution of three fibroblast growth factor receptor mRNAs during amphibian morphogenesis. AB - We have used in situ hybridization to survey the expression pattern of three fibroblast growth factor receptor (FGFR) mRNAs (PFR-1, PFR-3 and PFR-4, which we previously identified as the amphibian Pleurodeles waltl homologs of human FGFR 1, FGFR-3 and FGFR-4, respectively) during morphogenesis. Previous work suggests that these FGFR mRNAs exhibit a distinct pattern of expression at early developmental stages. In the present study we have tested the functional activity of these receptors and shown that both FGF-1 (acidic FGF) and FGF-2 (basic FGF), but not FGF-7 (keratinocyte growth factor), can lead to their activation, suggesting that the three cDNAs encode functional receptors. Results from in situ hybridization indicate that various FGFRs are involved in various developmental events. Their involvement in these processes is both overlapping and distinct. During the differentiation of the central nervous system (CNS), PFR-1 and PFR-4 mRNAs show high levels of redundant expression, while the sites of expression of PFR-3 mRNA correlate with regions, such as the diencephalon and the rhombencephalon, undergoing important anatomic changes. The three FGFR mRNAs are distinctly expressed in the cranial ganglia, the pigmented epithelia of retina and the otic vesicles. Most significantly, we found that they are strongly expressed at cranial and branchial mesenchymal condensation sites. PFR-3 mRNA is expressed earlier in this process than PFR-1 and PFR-4 mRNAs. Furthermore PFR-3 mRNA is detected in the mesenchyme of the limb bud, while PFR-1 and PFR-4 mRNAs are found in the primordia of the skeletal elements. In addition, PFR-1 mRNA is expressed in axial mesenchyme and PFR-4 mRNA is detected in the melanophores, xanthophores and in the pronephros. These results suggest that various FGFRs may be involved in distinct developmental events including cell proliferation and differentiation. We also discuss the functional redundancy of the FGFR system during amphibian morphogenesis. PMID- 7890138 TI - Cell type-specific desmosomal plaque proteins of the plakoglobin family: plakophilin 1 (band 6 protein). AB - Desmosomes represent a special type of the plaque-bearing adhering junctions, characteristic of certain pathways of cell differentiation, which compositionally are not identical in the various kinds of desmosome-forming cells. While all desmosomes contain the cytoplasmic plaque proteins desmoplakin I and plakoglobin, they can vary in their specific complement of desmosomal cadherins and by the presence of additional plaque proteins. We have raised monoclonal antibodies recognizing one such 'accessory' plaque protein, the cytokeratin-binding, basic protein plakophilin 1, originally introduced as 'band 6 protein' or 'polypeptide D6', which is an abundant desmosomal component in certain epithelia. Using such antibodies, we have isolated cDNA clones encoding the bovine and the human protein and determined their complete amino acid sequences. The mRNAs, which on Northern blot tests appear as two bands corresponding to approximately 4 and 2.4 kb (bovine) or 5 and 2.6 kb (human), code for 727 amino acids (calculated mol. wt. 80,180; IEP 9.25) in bovine and 726 amino acids (mol. wt. 80,496; IEP 9.34) in human plakophilin. Sequence analyses have revealed the presence of 9.2 repeated units of the arm-motif sequence, confirming our previous conclusion that this protein is a member of a larger family of proteins including, inter alia, several membrane-associated plaque proteins such as vertebrate plakoglobin and beta-catenin as well as the product of the armadillo gene of Drosophila. The plakophilin antibodies and cDNA probes have also allowed us to examine its synthesis in various tissues and cell cultures. While we confirm the occurrence of the protein in cytoskeletal fractions from various stratified squamous, complex, glandular duct and bladder epithelia, where it can be localized to desmosomes, we have, surprisingly, also identified the protein, although at lower amounts, in cytoskeletal fractions from several cultured cell lines in which the protein has not been consistently localized to desmosomes by immunofluorescence microscopy. Examples include cultured cells derived from certain simple epithelia such as the kidney-derived line MDBK and cultured calf lens cells. We have also found that, in all plakophilin 1-positive cells examined, a pool of diffusible ('soluble') cytoplasmic plakophilin exists, including cell lines such as human mammary carcinoma MCF-7 cells in which this soluble plakophilin seems to be the only detectable form. In addition, we have identified some soluble proteins conspicuously cross-reacting with plakophilin 1. Possible functions of plakophilin and its potential value as a marker for specific states of cell differentiation are discussed, particularly with respect to tumor diagnosis. PMID- 7890139 TI - Normal development, growth and reproduction in cellular retinoic acid binding protein-I (CRABPI) null mutant mice. AB - We have generated mouse null mutants for the cellular retinoic acid (RA) binding protein type I (CRABPI), a protein whose spatio-temporal expression pattern coincides with the target tissues for RA action. Inactivation of the CRABPI gene was accomplished via homologous recombination in embryonic stem cells. Cells carrying the correctly targeted gene were injected into blastocysts and the resulting chimaeras yielded offspring heterozygous for the knockout mutation. Subsequent breeding programs resulted in normal litter sizes containing viable and fertile CRABPI deficient mice. Homozygous mice carrying the knockout mutation were studied in detail to detect possible organ and skeletal anomalies and/or abnormalities of the hematopoietic system. No overt phenotype was evident indicating that a deficiency for CRABPI does not seem to interfere with normal development, growth and reproduction. PMID- 7890140 TI - Interactions between the transforming growth factor beta (TGF beta) and retinoic acid signal transduction pathways in murine embryonic palatal cells. AB - Regulation of expression of transforming growth factor-beta 3 (TGF-beta 3) and the cellular retinoic acid-binding proteins-I and II (CRABP-I, -II) by retinoic acid (RA) and TGF-beta was examined in primary cultures of murine embryonic palate mesenchymal (MEPM) cells. Northern blot hybridization revealed that RA and TGF-beta 1, beta 2 and beta 3 stimulated the expression of TGF-beta 3 mRNA within 24 hours of treatment. RA down-regulated the expression of CRABP-I mRNA and up regulated the expression of CRABP-II mRNA in a time- and dose-dependent fashion. TGF-beta 1, beta 2 and beta 3 also down-regulated the expression of CRABP-I mRNA, while epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) were without effect. TGF-beta 1 also stimulated a dose-dependent increase in the expression of CRABP-II mRNA. Again EGF and TGF-alpha were without effect. Basic fibroblast growth factor (bFGF) elicited a slight inhibitory effect on CRABP-II and a slight stimulatory effect on CRABP-I mRNA expression. Thus, cells derived from the mammalian developing palate express CRABP-I and CRABP-II mRNAs, both of which may be regulated by RA and TGF-beta. These data constitute the first demonstration of an effect of TGF-beta on the expression of CRABP-I and CRABP-II and provide further evidence for cross-talk between RA and TGF-beta signal transduction pathways. PMID- 7890141 TI - Osteogenin (bone morphogenic protein 3) inhibits proliferation and stimulates differentiation of osteoprogenitors in human bone marrow. AB - Treatment of human bone marrow osteoprogenitors with osteogenin (BMP-3; at 1, 2.5 and 10 ng/ml) caused dose- and time-dependent inhibition of DNA synthesis and cell proliferation. Simultaneously, osteogenin stimulated type I collagen synthesis and cAMP production. Addition of osteogenin to the cell culture increased intracellular alkaline phosphatase activity and osteocalcin synthesis, with maximal stimulation at 2.5 ng/ml. Simultaneous addition of 2.5 ng/ml osteogenin and 1,25 dihydroxy vitamin D3 (10(-8) M) enhanced the stimulation observed in osteocalcin synthesis. The experiments reported here demonstrate the significant "in vitro" influence of osteogenin in the stimulation of osteogenic phenotype in osteoprogenitor cells which have been isolated from human bone marrow and cloned. These results support a reciprocal relationship between cell growth inhibition and expression of osteoblast differentiation. PMID- 7890142 TI - Metabolic pathways for differentiation-inducing factor-1 and their regulation are conserved between closely related Dictyostelium species, but not between distant members of the family. AB - There is suggestive evidence that a conserved signalling system involving differentiation inducing factor-1 (DIF-1) controls stalk cell differentiation in a variety of slime mould species. In the standard laboratory species, Dictyostelium discoideum, DIF-1 is first inactivated by dechlorination catalysed by DIF-1 dechlorinase, then by several hydroxylation events, so that eventually about 12 metabolites are produced. If DIF-1 is used as a signal molecule in other species, they too must be able to metabolize it. We report here that the essentials of DIF-1 metabolism are conserved in D. mucoroides, the closest relative of D. discoideum. Both the dechlorinase and hydroxylase enzymes were present in D. mucoroides, and living cells of both species produced a similar spectrum of metabolites from [3H]DIF-1. Furthermore, DIF-1 dechlorinase was induced by DIF-1, as in D. discoideum, and this induction was repressed by ammonia and cAMP. DIF-1 dechlorinase could not be detected in cell extracts from D. minutum or Polysphondylium violaceum. However, living cells of both species are able to metabolize DIF-1; P. violaceum seems to produce a small amount of the monodechlorinated compound, DIF-3, but all other metabolites from both species appear to be unique. Thus all investigated species can metabolize DIF-1, but the exact route of metabolism is not highly conserved. PMID- 7890143 TI - Synergetic mechanisms of chiral symmetry breaking in prebiotic evolution. AB - It was shown on the Frank autocatalytic reaction-diffusion scheme that strong environmental fluctuations, conditioned by external noise (e.g. sunlight fluctuation) and external macroscopic flows (e.g. ebb and flow), typical for conditions on prebiotic earth, may have been beneficial for chiral symmetry breaking and formation and stabilization of biomolecular homochirality. PMID- 7890144 TI - Modulation of phospholipase A2 activity by membrane-active peptides on liposomes of different phospholipid composition. AB - To determine the influence of variations in both lipid species and lipid packing on phospholipase A2 (PLA2) hydrolytic activity, the activities of two PLA2 isolated from Crotalus molossus molossus venom, were followed on unilamellar liposomes modified by membrane-active peptides. Enzymatic activity was compared with cytolytic activity on human and mouse lymphocytes. Phosphatidylcholine liposomes were hydrolysed better than liposomes containing acidic phospholipids (phosphatidylserine, phosphatidic acid or cardiolipin) or phosphatidylethanolamine. Both membrane-active peptides, cardiotoxin and thionin, inhibited the PLA2 activity on phosphatidylcholine liposomes. The activities of the enzymes were profoundly enhanced on thionin-pretreated liposomes containing phosphatidylserine, and on cardiotoxin-pretreated liposomes containing cardiolipin or phosphatidic acid. Both cardiotoxin and thionin facilitated the cytolytic activities of PLA2 on both human and mouse lymphocytes. Cytolytic activity correlated well with esterase activity. It is proposed that the complex dynamic structure of cell membranes renders a variety of substrate configurations that transiently affect PLA2 activity. PMID- 7890145 TI - Time dependence of [3H]-vincristine accumulation by L1210 mouse leukemic cells. Effect of P-glycoprotein overexpression. AB - Overexpression of P-glycoprotein (P-GP) accompanied by multidrug resistance (MDR) to diverse groups of cytostatics was developed by long-term adaptation of mouse leukemic cell line L1210 to vincristine. Two resistant sublines of cells characterized by ID50 values for vincristine 1.05 mg/l (L1210/VCR-1) and 2.3 mg/l (L1210/VCR-2), respectively, were used. The sensitive parental cell line L1210 had the ID50 value for vincristine around 0.01 mg/l. Overexpression of P-GP induced by the adaptation procedure was found to be accompanied by an increase in the mean cell diameter from 10.28 +/- 1.60 microns (mean +/- SD, n = 122) for sensitive L1210 cells to 17.82 +/- 2.59 microns (n = 120) and 37.26 +/- 5.72 microns (n = 121) for L1210/VCR-1 and L1210/VCR-2 resistant cell sublines, respectively. Significant decrease in ability to accumulate [3H]-vincristine from cultivation medium was observed for both resistant cell sublines in comparison to sensitive cells. Accumulation of [3H]-vincristine by sensitive cells is secured only by passive diffusion of the drug across the plasma membrane. Contrary to that, active efflux of drug operating against its diffusion across the plasma membrane should be assumed as a factor influencing the [3H]-vincristine accumulation by resistant cells. Indeed, the time dependence of [3H]-vincristine accumulation by sensitive cells could be fitted using simple monoexponential kinetic dependence in contrast to biexponential kinetic dependences that are necessary for fitting [3H]-vincristine accumulation by both resistant cell sublines. Kinetic analysis of the experimental data indicates that accumulation of [3H]-vincristine by sensitive cells grows to a plateau reflecting probably the equilibrium of drug concentration in the intracellular and extracellular space. On the contrary, accumulation of [3H]-vincristine by both resistant cell sublines was stabilized after an initial growth on a considerably lower level than it was observed for the sensitive cells in the equilibrium. PMID- 7890146 TI - Changes in physical properties of ovarian membranes after hCG-induced desensitization in rats. AB - Using pseudopregnant rat ovaries, the possibility was examined whether hCG induced early desensitization of the LH/hCG receptor was accompanied by changes in the physical state of membranes. Thirty min after a single s.c. injection of 75 IU hCG, the hCG-responsive adenylylcyclase activity was reduced, whereas hCG binding to ovarian membranes was still normal. Membrane lipid rigidity, as determined by fluorescence polarization of DPH, decreased as early as 30 min after injection of a desensitizing dose of hCG. There was no difference in membrane rigidity when ovarian membranes were incubated 0.5 or 2 h with hCG or LH. The decrease of membrane lipid rigidity in the process of rapid desensitization of rat luteal tissue does not appear to be associated with protein synthesis. Desensitization also modified the differential scanning calorimetric profile. The results indicate that hCG-induced changes in the physical state of rat ovary membranes are preceded by the process of desensitization. PMID- 7890147 TI - Mode of action of psoralens, benzofurans, acridinons, and coumarins on the ionic currents in intact myelinated nerve fibres and its significance in demyelinating diseases. AB - The actions of psoralens, benzofurans, acridinons and coumarins on the ionic currents in intact myelinated nerve fibres were investigated. All 6 substances blocked the potassium currents in a time-dependent manner, producing so-called K+ transients. Only 5-methoxypsoralen is a largely selective blocker of predominantly the axolemmal potassium channels, which is the characteristic required by our previously proposed working hypothesis for the mechanism of potassium-channel blockers in demyelinating diseases, in particular multiple sclerosis. If the observed K+ transients were to arise by blocking of the potassium channels of the Schwann cell, that is, by the periaxonal accumulation of K+ and a resulting collapse of the electromotive driving force for potassium ions, according to a modified version of our previous hypothesis the other substances tested could also have a beneficial effect on the impaired impulse conduction in demyelinated axons. In this case a large number of new potential drugs would be available for the symptomatic therapy of MS. PMID- 7890148 TI - Mechanism of inhibitory action of the local anaesthetic trimecaine on the growth of algae (Chlorella vulgaris). AB - Using the model compound trimecaine, it was found that algicidal effects exhibited by the local anaesthetics of the acetanilide type were caused by two different mechanisms. The first inhibitory mechanism occurring at low concentrations of the anaesthetic is connected with the uncoupling of the photophosphorylations in algal chloroplasts and is accompanied by the enhancement of the oxygen evolving rate in algal photosynthesis. The second mechanism of inhibition of the photosynthesis in algae, taking place at higher concentrations of the anaesthetic, is connected with the damaging of the manganese containing protein on the donor side of photosystem 2 and is accompanied by a decrease of the oxygen evolving rate in algal photosynthesis. PMID- 7890149 TI - [Study of protein products of gene expression in cells with altered chromosome sets for genetic mapping]. AB - Two-dimensional electrophoresis was used for analyzing proteins in hybrid cells that contained single human chromosomes (chromosome 5, chromosome 21, or chromosomes 5 and 21) against the background of the mouse genome. By comparing the protein patterns of hybrid and parent cells (about 1000 protein fractions for each kind of cell), five fractions among proteins of hybrid cells were supposedly identified as human proteins. The genes of two of them are probably located on chromosome 5, and those of other three, on chromosome 21. Moreover, analysis of proteins in fibroblasts of patients with the cri-du-chat syndrome (5p-) revealed a decrease in the content of two proteins, as compared with those in preparations of diploid fibroblasts. This fact was regarded as evidence that two corresponding genes are located on the short arm of chromosome 5. Methodological problems associated with the use of protein pattern analysis in cells with altered chromosome sets for the purposes of genetic mapping are discussed. PMID- 7890150 TI - [The ard gene, coding for a type I restriction inhibitor, is present in plasmids of FII, B/O, and K-groups of incompatibility]. AB - The effect of conjugative plasmids of various incompatibility groups of the enterobacteria family on the activity of the cell restriction-modification system of type I (EcoK) was studied. Twenty-two conjugative plasmids of 15 incompatibility groups were tested. In addition to plasmids of the incI1 and incN groups studied earlier, conjugative plasmids of the incFII, incB/O, and incK groups were also shown to be able to weaken the action of type I restriction enzymes upon nonmodified DNA (Ard phenotype). A hybridization analysis of all the plasmid DNAs studied, using ard gene DNA sequences from the ColIb-P9 (incI1) plasmid as a probe, was performed. The ard locus of the R100 (incFII) plasmid was cloned in the pBR322 and pACYC184 vectors. The ard gene was located 2.5 kb from the oriT site in the leading region on the R100 conjugative plasmid. PMID- 7890151 TI - [Analysis of DNA polymorphism detected by genomic fingerprinting based on phage M13 DNA, in populations of Bashkir and Komi]. AB - Hyperpolymorphism of minisatellite DNA, detected using the M13 bacteriophage DNA hybridization probe, was studied in three ethnographic groups of Bashkirs and in the Komi population. Bands from 2 to 20 kb were analyzed in hybridization patterns. A significant population difference was detected both in evaluation of the average number of hybridization fragments per individuals and in the distribution of frequency of some fractions. Thus, it seems possible to describe a set of so-called characteristic fractions for each population. According to the hybridization fragment frequency for the populations investigated, an index of genetic similarity was calculated. The possibility of using this kind of multiple polymorphism of DNA in population genetic investigations at the level of ethnic groups and peoples is discussed, and a conclusion is made about the necessity of searching for the most informative methods of analyzing the data obtained. PMID- 7890152 TI - [The primary structure of a vaccine strain of tobacco mosaic virus V-69]. AB - A random set of cDNA fragments were synthesized on genomic RNA of TMV vaccine strain V-69, using random primers and reverse transcriptase. Following synthesis of double-stranded cDNA, they were cloned into the pUC-19 plasmid; and 28 clones were sequenced (insert size 100-500 bp). High nucleotide sequence homology of V 69 (more than 95%) was shown only with tomato strain TMV-L [1]. Sequenced clones represent 54% of the genome (50% of the replicase gene, 98% of the transport protein gene, and 60% of the coat protein gene). In this genome region, 24 base substitutions were revealed, as compared to the wild-type TMV-L sequence. Six base substitutions resulted in changes in corresponding amino acid codons. No substitutions coincided with those discovered in the related TMV vaccine strain L11A [2], while two substitutions in the replicase gene were identical to those found in TMV strain Lta1 [3], which is capable of overcoming protection in tomatoes with the resistance gene Tm-1. PMID- 7890153 TI - [Structural mutations of chromosome mutations induced by heavy metal salts during aging in vivo and in vitro]. AB - The cytogenetic effect of inorganic copper (CuSO4) and cadmium (CdCl2) salts was studied in cells of long-term (144-hour) human cultures (in vitro model of aging) and in elderly individuals (80-93 years old). Copper sulfate increased the incidence of aberrant cells both in elderly individuals (14.25 +/- 1.74%) and during in vitro aging (12.20 +/- 1.62%) (3.94 +/- 1.96% and 5.25 +/- 1.10% in the controls, respectively), whereas treatment with cadmium chloride did not induce any changes in the background index. Differences in the effect of the studied salts may be due to their different effects on chromatin modification. PMID- 7890154 TI - [Mutagenesis and interchromosomal effect on crossing over in Drosophila]. AB - The possibility of mutational consequences of interchromosomal effect on crossing over was studied in Drosophila melanogaster females with four genotypes: (1) structurally normal (control); (2) heterozygous at In(1)-Muller-5 inversion (X chromosome); (3) heterozygous at In(3LR)CxD inversion (chromosome 3); and (4) heterozygous at both inversions. The mutational effect was determined through the loss of autosome 2 and formation of arm compounds C(2L) and C(2R). In females with recombinations, the rate of mutational events did not exceed that of the control. It was concluded that interchromosomal effect on crossing-over is of a regulatory character and disturbs neither recombination itself nor chromosome pairing. Coorientation X-3 leading to the appearance of intersexes in the progeny occurred in meiosis in females with two inversions. PMID- 7890155 TI - Unusual folding regions and ribosome landing pad within hepatitis C virus and pestivirus RNAs. AB - A statistically significant folding region is identified in the 5' untranslated region (5'-UTR) of hepatitis C virus (HCV), bovine viral diarrhea virus and hog cholera virus. This unusual folding region (UFR) detected in HCV encompasses 199 nucleotides (nt) and coincides with the reported internal ribosome entry site or ribosome landing pad (RLP), as determined by the 5' and 3' deletions [Tsukiyama Kohara et al., J. Virol. 66 (1992) 1476-1483]. The RNA structure predicted in the UFR of HCV consists of a large stem-loop and a pseudoknot. The proposed structural model is consistent with RNase sensitivity studies [Brown et al., Nucleic Acids Res. 20 (1992) 5041-5045]. Moreover, the structure is highly conserved among these divergent HCV and pestivirus RNAs. The covariation of paired bases in the helical regions offers support for the proposed structural models. The pseudoknot predicted in these UFR shares a similar structural feature to those proposed in the RLP of cardioviruses, aphthoviruses and hepatitis A virus. Based on the common structural motif, a putative base-pairing model between HCV RNA and 18S rRNA, as well as pestiviral RNAs and 18S rRNA are suggested. Intriguingly, the proposed base-pairing models in this study are comparable to those proposed in picornaviruses in terms of their folded shape and location of the predicted complementary sequences between viral RNAs and 18S rRNA. Taken together, we suggest that the common base-pairing model between the UFR detected in the 5'-UTR of pestivirus and HCV and 18S rRNA have a general function in the internal initiation of cap-independent translation. PMID- 7890156 TI - Sequence of the cDNA and gene coding for ribosomal protein S1 of Xenopus laevis. AB - The cloning and complete sequencing of one of the two gene copies coding for ribosomal protein (r-protein) S1 in Xenopus laevis and of the corresponding cDNA are reported. The comparison of the sequence of this cDNA (S1b) with the other (S1a) previously reported, reveals that, while the two DNA sequences have diverged somewhat, the amino-acid sequences are mostly unchanged. The two gene copies are apparently expressed at comparable levels, since the two corresponding mRNAs are similary represented in oocyte poly(A) RNA. The S1b gene has a total length of about 12000 nt and is composed of seven exons and six introns. By primer extension, it has been determined that the transcription start point is located in a pyrimidine-rich tract, as observed for all r-protein genes of X. laevis and other vertebrates so far analyzed. A computer analysis of the S1 sequence has shown the presence of a 150-nt sequence repeated in introns 3, 5 and 6, which is homologous to the one reported in the first intron of mammalian r protein S3 gene. Furthermore, a 130-nt sequence is tandemly repeated 2.5 times at each of the two sites near the beginning and near the end of the first intron. PMID- 7890157 TI - Two gene duplication events in the human and primate dopamine D5 receptor gene family. AB - The human dopamine D5 receptor (DRD5) gene family consists of the DRD5-encoding gene (DRD5) and the pseudogenes psi DRD5-1 and psi DRD5-2. Analysis of the 5' UTR of DRD5 and homologous regions in the pseudogenes revealed that the nucleotide identity (approx. 95%) extended for 1.9 kb and terminated at a monomeric Alu sequence in each of the pseudogenes. The presence of Alu sequences in the pseudogenes, at this point of divergence with DRD5, suggests that Alu sequences were involved in the evolution of the DRD5 family. This report is the first to describe a possible mechanism involved in the duplication of genes in the G protein-coupled receptor (GPCR) family. The pseudogenes continue to share identity (approx. 98%) beyond this 5' UTR point of divergence with DRD5 for at least another 6 kb. Analysis of the 3' UTR of DRD5 and homologous regions in the pseudogenes revealed that the identity (approx. 95%) extends at least 14 kb, and the identity between the pseudogenes (approx. 98%) extends for at least 18 kb. Thus, the duplication unit that produced the first pseudogene was at least 16 kb, whereas the second pseudogene was at least 28 kb. We have also located two DRD5 pseudogenes in gorilla demonstrating that these closely related pseudogenes were present in a common ancestor of human and gorilla. PMID- 7890158 TI - Total synthesis and expression in Escherichia coli of a gene encoding human tropoelastin. AB - To elucidate the structural features and interactions of tropoelastin (TEL) molecules which assist in giving the elastic fibre its physical properties, a 2210-bp synthetic human TEL-encoding gene (SHEL) was constructed for expression in Escherichia coli. To this end, a model of codon adjustment was tested which better suits the polypeptide biosynthetic needs of E. coli than the human sequence, where over one-third of this natural sequence contains expression limiting rare codons and 4 amino acids alone account for 75% of the resulting polypeptide. This large synthetic TEL gene was expressed at a high level as the recombinant counterpart of human TEL and as a C-terminal fusion with glutathione S-transferase. This demonstrates that a synthetic approach based upon matching codon usage to that of the host organism can support significant expression of recombinant sequences. The synthetic gene incorporates the facility for simple cassette replacement in future insertion, deletion and mutagenesis experiments, including the introduction and removal of exon homologues. The resulting soluble polypeptide is easily purified and displays properties expected for this protein. PMID- 7890159 TI - Exogenously added copper does not increase the production of copper amine oxidase in lentil seedlings. AB - The effect of copper ions, the inorganic cofactor of amine oxidase (AO; EC 1.4.3.6), on the production of this enzyme in lentil (Lens culinaris) seedlings was studied. The addition of CuSO4 to the imbibition water during the germination of lentils increased the AO activity. However, the amounts of specific mRNA and protein were not affected by the presence of Cu2+. Furthermore, the addition of Cu2+ to homogenates of lentil seedlings grown in the absence of the metal substantially increased the AO activity. Therefore, it appears that exogenously added Cu2+ does not increase the production of AO in lentil seedlings which are still able to synthesize the copper-free enzyme. The addition of Cu2+ seems to reconstitute the enzymatically active holoprotein. PMID- 7890160 TI - Sequence of the new Drosophila melanogaster small heat-shock-related gene, lethal(2) essential for life [l(2)efl], at locus 59F4,5. AB - In this study, we report the molecular cloning of a novel Drosophila melanogaster small heat-shock (HS)-homologous gene, l(2)efl, identified on the right arm of the second chromosome at locus 59F4,5. We describe the temporal expression of l(2)efl in the wild-type and present its structure. The deduced amino-acid sequence of the Efl protein shows significant homology to all known small HS proteins identified in Drosophila and vertebrates, and to mammalian alpha crystallin. PMID- 7890161 TI - Genetic and molecular analysis of terminal deletions of chromosome 3R of Drosophila melanogaster. AB - Terminal deletions of chromosome 3R are induced at a high frequency (3.2 x 10( 3)) by irradiating 45-4 Drosophila melanogaster females with a low dose of X rays. The 45-4 line carries a white transgene inserted at 16 kb from the terminus and is homozygous for the mu-2 mutation, a gene involved in the repair of double strand DNA breaks. Four of the 51 recovered deleted strains have lost modulo, the distalmost essential gene on chromosome 3R. Breakpoints of 22 deletions have been localised in a single hybridisation step, using pulsed-field gel electrophoresis to separate genomic DNA fragments obtained from digestion with a rare-cutter restriction enzyme. Breaks do not occur at random, but are rather clustered in three susceptible chromosomal domains. Backcross experiments resulting in transheterozygous (deleted chromosome/45-4) animals indicate that the activity of the white transgene is enhanced when the DNA break has occurred proximal to a critical position. This suggests that homologous chromosomal pairing distal to the critical position results in the definition of a more compact chromatin structure and, due to position effect, in the silencing of white. PMID- 7890162 TI - Cloning and sequence analysis of GmII, a Drosophila melanogaster homologue of the cDNA encoding murine Golgi alpha-mannosidase II. AB - Using the murine cDNA that encodes Golgi alpha-mannosidase II (GlcNAc transferase I-dependent alpha 1,3[alpha 1,6] mannosidase; EC 3.2.1.114) as a probe to screen a cDNA library made from Drosophila melanogaster (Dm) embryos, we have isolated GmII, the Dm sequence homologue. The 3926-bp cDNA has an open reading frame of 3327 bp and predicts a polypeptide of approx. 127 kDa, a mass similar to that of the murine protein. The deduced mouse and Dm amino acid (aa) sequences share extensive similarity across their entire lengths and are both type-II transmembrane (TM) proteins with short cytoplasmic tails, single TM domains and large hydrophilic C-terminal domains. A region of approx. 200 aa, within the C terminal domain, has considerable similarity to a corresponding region from several other alpha-mannosidases. GmII has been localized to a single site (85D14 18) on the right arm of chromosome 3. PMID- 7890164 TI - Xenopus laevis ribosomal protein L22: full-length cDNA sequence and expression analysis. AB - A cDNA clone was isolated from a Xenopus laevis embryo library and sequenced. Primer extension experiments indicated the full-length nature of the insert and the encoded product was identified on a two dimensional gel as ribosomal protein (r-protein) L22. The 510-bp L22 cDNA sequence presents short untranslated regions and a 5'-end polypyrimidine tract found in all other vertebrate r-protein mRNA (rp mRNA) so far analyzed. Both the nucleotide (nt) and the deduced amino acid (aa) sequences have been compared with the homologous sequences from other species. The L22 nt sequence is about 70% similar to the mammalian L27a rp mRNA and about 60% homologous to the Drosophila, Tetrahymena and yeast corresponding mRNAs. The 148-aa sequence presents a higher conservation, being 90% similar to the mammalian sequence and more than 70% to the other species. Expression analysis showed that, both during X. laevis embryogenesis and in X. laevis cultured cells during growth-rate changes, L22 synthesis is translationally regulated. Therefore X. laevis L22 mRNA is a new example of the correlation between the polypyrimidine terminal tract and the translational regulation observed in other rp mRNAs. PMID- 7890163 TI - Novel Drosophila melanogaster genes encoding RRM-type RNA-binding proteins identified by a degenerate PCR strategy. AB - We are interested in identifying Drosophila melanogaster RNA-binding proteins involved in important developmental decisions made at the level of mRNA processing, stability, localization or translational control. A large subset of the proteins known to interact with specific RNA sequences shares an evolutionarily conserved 80-90-amino-acid (aa) domain referred to as an RNA recognition motif (RRM), including two ribonucleoprotein identifier sequences known as RNP-1 and RNP-2. Hence, we have herein applied degenerate polymerase chain reaction (PCR) methodology to clone three additional members (termed rox2, rox8 and rox21) of the D. melanogaster RRM-protein gene superfamily encoding putative trans-acting regulatory factors. Representative cDNA clones were isolated, the conceptual aa sequences of the candidate Rox proteins were inferred from their nucleotide sequences, and database searches were conducted. Rox2 displays extensive aa sequence similarities to putative RNA-binding proteins encoded by the genomes of the plants Oryza sativa and Arabidopsis thaliana; Rox21 resembles essential metazoan pre-mRNA splicing factors; as described elsewhere, Rox8 is likely a fly homolog of the two human TIA-1-type nucleolysins [Brand and Bourbon, Nucleic Acids Res. 21 (1993) 3699-3704]. PMID- 7890165 TI - Isolation and characterization of a cDNA encoding a chicken actin-like protein. AB - We report the isolation and characterization of a chicken cDNA which putatively encodes an actin-like protein (chACTL). This 394-amino-acid (aa) polypeptide shares sequence homology (81, 70 and 67% identical aa, respectively) with three actin-related proteins (ARP) described for Drosophila melanogaster (ARP14D), Caenorhabditis elegans (ACTL) and Saccharomyces cerevisiae (ACT2). At least six chACTL transcripts were detected in different tissues during chick embryogenesis. Sequence analysis suggests that at least three groups of ARP have been evolutionarily conserved. PMID- 7890166 TI - Sequence of a cDNA encoding chicken vasoactive intestinal peptide (VIP). AB - Mammalian pre-pro-vasoactive intestinal peptide (pre-proVIP) gives rise to the neuropeptides vasoactive intestinal peptide (VIP) and peptide histidine isoleucine amide (PHI). The cDNA encoding chicken VIP was cloned and sequenced. The region of chicken pre-proVIP homologous to the mammalian PHI region is not followed by an amidation signal. This unusual feature suggests that processing of the precursor may be different in the chicken. PMID- 7890167 TI - Characterization of the 5' flanking region and gene encoding the mouse interferon gamma receptor. AB - The purpose of this investigation was to characterize the gene that encodes the receptor for mouse interferon-gamma (IFN-gamma R), including determination of its size, intronic boundaries and its transcription start points (tsp). The mouse IFN gamma R gene is 22-kb long, with six introns that range in size from approx. 1 to 7 kb. The first six exons encode the extracellular and transmembrane (TM) domains of the protein, while the last exon of about 1 kb encodes most of the intracellular domain. No canonical TATA box can be found in the 5' flanking sequence of the gene, and primer extension analysis indicates multiple tsp. In addition, the gene's 5' promoter region was sequenced to identify candidate responsive elements that might regulate expression of the gene. Among the putative regulatory motifs identified by computer-assisted analysis are multiple SP1 and AP-2 sites, an NF1 and CCAAT box, as well as a potential cyclic AMP responsive element (CRE). PMID- 7890168 TI - Discovering genes with localised expression in the mouse brain: cDNAs specific to the substantia nigra. AB - Many important phenomena of normal brain physiology and disease are likely to be related to the function of genes expressed in localised regions of the brain. We show that subtracted libraries enriched in clones corresponding to rare mRNAs, which must include genes with very localised and neuron-specific expression, can easily be produced from single-stranded directional cDNA libraries after hybridization to excess photobiotinylated opposite-stranded cDNA (or RNA) from another brain region, followed by the removal of biotinylated molecules. We also demonstrate the use of heterologous probes from anatomically precise small regions of bovine brain to identify cDNA clones that putatively represent mRNAs present at significantly higher levels in a substantia nigra mRNA population enriched for pars compacta mRNA than in the total ventral midbrain or cerebellar mRNA population. Some of these cDNAs may identify genes that play important roles in the specific molecular biology of dopaminergic neurons, including susceptibility to Parkinson's disease. PMID- 7890169 TI - The eighth Cct gene, Cctq, encoding the theta subunit of the cytosolic chaperonin containing TCP-1. AB - The chaperonin containing t-complex polypeptide 1 (TCP-1), as one of its subunits, CCT, is a cytosolic heterooligomeric molecular chaperone assisting in the folding of proteins in eukaryotic cytosol. We have isolated a Tcp-1-related 119-bp cDNA fragment from a human cDNA library by polymerase chain reaction, and cloned full-length mouse cDNAs orthologous to the human cDNA by hybridization. The nucleotide (nt) sequence of the longest mouse clone (1844 bp) shows an open reading frame (ORF) encoding a TCP-1-related polypeptide of 548 amino acids (aa) (59,562 Da). This gene is different from Tcp-1 and the six Tcp-1-related genes reported previously, Tcp-1 (Ccta), Cctb, Cctg, Cctd, Ccte, Cctz and Ccth, which encode subunits of CCT. The product of the novel gene was analysed using an antibody raised against the C terminus of the polypeptide deduced from the nt sequence. We found that this gene encodes a subunit of CCT (polypeptide S1; 62 kDa and pI 6.25 by two-dimensional gel analysis). We have named it Cctq, encoding the theta subunit of CCT (CCT theta). The aa sequence of CCT theta shows 23-29% identity to the other CCT subunits, alpha, beta, gamma, delta, epsilon, zeta and eta, and 29% identity to the archaebacterial chaperonin TF55. CCT theta also contains the motifs common to all the other subunits of CCT which are postulated to be involved in ATPase activity. PMID- 7890170 TI - Organization, sequence and regulation of expression of the murine Hoxa-7 gene. AB - The genomic sequence of Hoxa-7 (encoding the HOXa-7 homeobox protein), including the coding region (0.7 kb), flanked by a 5'-upstream region (2.8 kb), a 3' downstream region (1 kb) and interrupted by an intron (995 bp), was determined. Northern blot analysis indicated the transcript size of Hoxa-7 to be 2.1-2.4 kb. Reverse transcription-PCR and primer extension analysis established the 5' boundary of the mRNA to be in the region 1166 nt upstream from the start codon. Transient transfection of various Hoxa-7::cat constructs in NIH 3T3 cells was used to characterize the transcriptional activity of the 5'-flanking region of the gene. Constructs containing 544, 274 and 71 bp of the region upstream from the transcription start point (tsp) exhibited 78, 203 and 407%, respectively, of the activity shown by a control construct containing 739 bp of the upstream region. These data suggested the presence of negative regulatory elements in the region from 544 to 71 bp upstream from the tsp. PMID- 7890171 TI - Genomic organization and promoter sequence of a gene encoding a rat liver specific type-I transport protein. AB - We report the isolation and characterization of a rat gene (designated TI-LTP) encoding a liver-specific cell-surface glycoprotein that belongs to the type-I transporter family. This gene, including 5' and 3' flanking domains, was cloned from a rat lambda DASH genomic library and its nucleotide sequence was determined. TI-LTP is a single-copy gene which spans over 6 kb, and contains nine introns ranging in size from 90 bp to over 1.8 kb. Two transcription start points were located using a nuclease S-1 protection assay. The TI-LTP promoter (pTI-LTP) lacks a canonical TATA-box element, but does contain five TAGA elements. Several putative transcription-factor-binding sites were identified in the pTI-LTP, including activator protein 2 (AP-2) sites and a peroxisome proliferator response element (PPRE). PMID- 7890173 TI - Primary structure of the canine U1 snRNA. AB - The nucleotide (nt) sequence of the canine U1 snRNA was determined. It exhibited significant homology (90-98%) with known U1 sequences. The RNA can be folded according to the secondary structure previously proposed for the U1 snRNA. It contained the conserved sequence UUACCUG in loop A (nt 6-12), required for the recognition of the 5' splice site, and the sequence UGCACU in loop B (nt 68-73), required for recognition of the U1-70K protein. The U1 snRNA was localized in the nucleus and its transcription was sensitive to alpha-amanitin, suggesting that it is transcribed by RNA polymerase II. Southern analysis revealed that the canine genome possesses 5-10 copies of U1 snRNA-encoding genes. PMID- 7890172 TI - A regulatory element downstream of the rat SM22 alpha gene transcription start point enhances reporter gene expression in vascular smooth muscle cells. AB - SM22 alpha is a 22-kDa protein of unknown function, the mRNA of which is highly and specifically expressed in smooth muscle cells (SMC). The 5' untranslated leader sequence of the rat SM22 alpha gene was found to contain two introns of 3.6 and 2.9 kb. Two transcripts of SM22 alpha exist in all SMC types examined, and genomic mapping of the gene suggests these transcripts result from different 5' transcription start points, split by the 2.9-kb intron. A small intron (102 bp), which contains an E-box consensus sequence, was found within the coding region 178 bp from the ATG start codon. The 3.6-kb intron contains 82 bp which show 98% homology at the RNA level with the rat identifier sequence (ID). Transient reporter gene assays demonstrate that a 576-bp fragment, including the ID, contains a regulatory element which may contribute to the SMC-specific expression of SM22 alpha. PMID- 7890174 TI - Complete sequence of the ovine beta-casein-encoding gene and interspecies comparison. AB - The 9149-bp transcription unit encoding ovine beta-casein (Cas) and 4636 bp of 5' flanking region were completely sequenced. The gene is composed of nine exons and its overall organization is similar to that of its counterparts from other species. Intron 4, the largest, shares three similar stretches (sizes ranging from 0.1 to 0.3 kb) with the region upstream from the transcription unit. These common sequences are part of short interspersed nuclear elements (SINE) specific to Bovidae (Bov). Intron 4 contains two 274-bp Bov-A2 SINE in opposite orientation, as well as a full-length 569-bp Bov-B SINE. This latter SINE, also present in caprine intron 4, is missing in cattle. This suggests that the amplification of Bov-SINE has continued after the divergence of cattle from sheep and goats, assuming that the presently known sequences are representative of these species. PMID- 7890176 TI - Cloning and characterisation of multiple acetyl-CoA carboxylase transcripts in ovine adipose tissue. AB - A full-length ovine acetyl-CoA carboxylase-encoding cDNA (ACC) has been cloned from adipose tissue and completely sequenced. The open reading frame of 7041 nucleotides (nt) is highly homologous to the previously cloned human, rat, chicken, yeast and algal ACC (85, 89, 82, 54 and 54% identity, respectively). Transcript heterogeneity was found in the 5' and 3' untranslated regions (UTR) resulting in ACC transcripts in the range of 9.0 kb to 9.4 kb. Heterogeneity at the 5' end was generated by the insertion of a 47-nt sequence, resulting in transcripts with either 272 or 319 nt in the 5'-UTR. Heterogeneity at the 3' end was the result of the use of different polyadenylation signals. RNase protection analysis demonstrated that shorter transcripts containing 1635 nt predominated over longer transcripts of 2065 nt in the 3'-UTR. PMID- 7890175 TI - Cloning and expression of a cDNA encoding ovine interleukin 7. AB - Using the polymerase chain reaction (PCR) and primers based on regions of homology between the human and murine interleukin 7 (IL-7)-encoding cDNAs, we have amplified an ovine (ov) IL-7 cDNA from reverse-transcribed RNA extracted from concanavalin A (Con A)-activated ovine lymph-node cells. The nucleotide sequence of the cDNA and the predicted amino acid (aa) sequence showed significant homology to those of the human and murine molecules. The ovIL-7 cDNA encodes a 176-aa polypeptide that, based on analysis of murine IL-7, is processed to a protein of 151 aa. The cDNA was demonstrated to encode a protein with IL-7 biological activity. Supernatants from COS or CHO-K1 cells transfected with an expression vector containing the ovIL-7 cDNA were able to synergise with a suboptimal level of Con A to induce proliferation of ovine thymocytes. In addition, both supernatants were able to induce thymocyte proliferation, albeit at a reduced level, in the absence of Con A. Further experiments demonstrated that for induction of ovine thymocyte proliferation, recombinant (re)-ovIL-7 was able to synergise with re-human (h) IL-2 but not re-hIL-6 or tumor necrosis factor-alpha (re-hTNF alpha). PMID- 7890177 TI - Evolutionary conservation in the DNA-binding and -bending properties of HMG-boxes from SRY proteins of primates. AB - Mammalian sex determination is caused by the Y-chromosome gene SRY, which encodes a protein containing a DNA-binding domain (HMG-box) of about 70 amino acids (aa). The HMG-box is very conserved in a wide variety of mammals; conversely, the flanking non-box regions show a high degree of aa sequence divergence, even between closely related species. The HMG-box of human SRY binds sequence specifically to linear DNA and produces a sharp bend; it also interacts with high affinity to kinked DNA structures irrespective of their sequences. Point mutations associated with sex reversal in XY human females fall within the HMG box and either affect the affinity for DNA or modify the geometry of the DNA protein complex. Here, we show that the DNA-binding and -bending properties of the HMG-boxes of SRY from human and seven different primates are extremely similar to each other. Together with other data, this suggests that the inability of mouse and human SRY to substitute for each other is due to differences in the conserved HMG-box, rather than the non-conserved flanking sequences. PMID- 7890178 TI - Novel aromatase transcripts from bovine placenta contain repeated sequence motifs. AB - Aromatase cytochrome P-450 (Aro) is the major enzyme of estrogen biosynthesis. The aim of the present investigation was the isolation and comparative sequence analysis of the bovine aromatase cytochrome P-450 transcript (bCyp19) from a placental lambda gt10 cDNA library. From three overlapping clones, a total sequence of 5180 bp could be derived, including two polyadenylation sites and signals located next to each other. As found in other species, the open reading frame (ORF) comprises 1509 bp and shows 87, 78 and 78% sequence homology to the coding areas of the human, rat and mouse genes, respectively. The 3'-untranslated region (UTR) of the bovine transcript is about 2-kb longer than that of the human gene (hCYP19). It contains homologous retroposon elements of the bovidae dimer family (BDF) at two different positions, and ends with a sequence motif which also occurs repeatedly within the bovine genome. The 5'-UTR isolated from placenta includes a new sequence upstream from exon II that was not found in cattle or other species so far. We conclude from our data that (i) as found in other species, bCyp19 is likely to be transcribed into different mRNA species, (ii) the bovine 3'-UTR was the target for multiple insertions of repeated sequence motifs, (iii) the unusual length of the bCyp19 transcript is mainly due to the long 3'-UTR, (iv) it includes sequences which are found in humans only on the genomic level, conceivably due to mutational inactivation of a primordial polyadenylation signal (PAS) and (v) the recently used, functional PAS is contributed by a downstream bovine repeat element. PMID- 7890179 TI - An aromatase pseudogene is transcribed in the bovine placenta. AB - The present investigation is focused on a new, truncated bovine aromatase cytochrome P-450-encoding transcript (bCyp19) which was repeatedly isolated from a placental lambda gt10 cDNA library. Different cDNA probes derived from bCyp19 were used during screenings. The deviant transcript contains areas of considerable sequence homology (89-98%) corresponding to exons II, III, V, VIII and IX of bCyp19. Exons VI and VII are missing. Exon IV is replaced by a bovine repeat sequence motif. Numerous translation stop codons occur within all reading frames, thus suggesting that the transcript does not encode a functional protein. The gene was detected by PCR in the genomes of all animals investigated (n = 38). The experiments demonstrate that the bovine genome contains a non-functional copy (pseudogene, Cyp19 phi) of bCyp19 that is transcribed together with the bCyp19 messenger in the bovine post-parturition placenta. PMID- 7890180 TI - Sequences of the 18S rDNAs from two Collembolan insects: shorter sequences in the V4 and V7 regions. AB - The complete 18S rDNA sequences were determined for Hypogastrura sp. and Crossodonthina koreana (Insecta: Collembola) using PCR cloning and Taq dideoxy sequencing. These two wingless insects show high sequence similarity to each other, without large insertions and/or deletions, and are clearly distinguished from the two dipteran insects Drosophila melanogaster and Aedes albopictus by shorter sequences in the V4 (61-76 bp) and in the V7 (89-104 bp). regions. PMID- 7890181 TI - Sequences of two cDNAs encoding silkworm homologues of Drosophila melanogaster squid gene. AB - The squid (sqd) gene of Drosophila melanogaster encodes a few isoforms of a heterogeneous nuclear (hn) RNA-binding protein. We isolated two types of cDNAs coding for homologues of the Sqd protein from the silkworm Bombyx mori. The two predicted amino acid (aa) sequences are identical up to aa 280 and then diverge. The silkworm and fruit fly proteins share 80% homology in the RNA-binding motif region. These cDNAs detect 2.0-, 1.8- and 1-kb mRNAs in the middle and posterior silk glands. PMID- 7890182 TI - Cloning and expression of the cDNA encoding rabbit liver carbonyl reductase. AB - Two cDNA sequences encoding rabbit carbonyl reductase (CBR) were cloned from a lambda gt10 rabbit liver cDNA library. The rabbit cDNAs coded for a protein with 84% identity to human CBR. Transient expression of the two rabbit cDNA sequences in COS7 cells increased both quinone reductase and aldo-keto reductase activities. These data demonstrate that CBR cDNAs from rabbit and human tissues code for similar proteins. PMID- 7890183 TI - Human Y-box transcription factors: sequences of two new YB-1 alleles. AB - The complete nucleotide (nt) sequences of two new alleles of the human Y-box binding protein are described. These alleles show over 93% nt similarity to published sequences of YB-1. PMID- 7890184 TI - Edward W.D. Norton. PMID- 7890185 TI - Clinical heterogeneity of dominant optic atrophy: the contribution of visual function investigations to diagnosis. AB - BACKGROUND: The variability of the visual function impairment in dominant optic atrophy (DOA) makes it difficult to diagnose the disease within genealogies. Physiologic investigations were conducted on a family with DOA to evaluate methods of detecting clinical and subclinical signs in obligate heterozygotes, in order to identify affected subjects within the genealogy and to formulate the individual and reproductive risks. METHODS: Investigations included tests for color vision, contrast sensitivity function (CSF), kinetic and static computerized perimetry, transient pattern reversal visual evoked potentials (VEPs) and steady-state flash VEPs. RESULTS: Eight subjects from the pedigree were diagnosed as having DOA. Two of them were unaware of their affection, and six showed wide clinical variability. CSF paralleled the central visual impairment, but was also slightly impaired in the two unaware subjects. Static computerized perimetry disclosed mild sensitivity defects in the central visual fields in these two patients. VEPs showed heterogeneous results as well, ranging from normal findings to severely altered tracings. CONCLUSIONS: This investigation suggests that combined clinical and functional evaluation is necessary to diagnose DOA. Particularly, the combined use of computerized perimetry, CSF, and VEPs allowed the identification of cases at a subclinical stage. PMID- 7890186 TI - Ocular findings in trigonocephaly. AB - BACKGROUND: Trigonocephaly, caused by premature closure of the metopic suture, is a rare form of craniosynostosis. The aim of this study was to assess the visual outcome in children operated on for trigonocephaly. METHODS: We present eight cases of children with trigonocephaly surgically corrected by the same craniofacial technique. CT with 3D reconstruction was performed in all cases. Genitori defined three types of trigonocephaly according to the severity of the deformity of the skull base only types II and III were included in this study directed at evaluation of the ocular disorder. A complete eye examination was performed on all children by the same observer, with a follow-up of 2-6 years. RESULTS: 3D-CT reconstruction of the skull base showed that the frontozygomatic region was affected by the deformation. Ocular examination showed considerable astigmatism in most children with late operation. A low degree of strabismus was observed in most children. CONCLUSION: This study demonstrated that reconstructive surgery should be performed by the age of 6 months, given the immaturity of the visual system up to that time. Close cooperation between neurosurgeons, pediatricians and ophthalmologists is of paramount importance in order to prevent this bone deformation exerting an adverse effect on visual development. The ophthalmologist must possess a basic understanding of the various craniosynostoses. PMID- 7890187 TI - Sebaceous gland adenoma of the palpebral conjunctiva in a patient with Muir-Torre syndrome: a case report. AB - BACKGROUND: Muir-Torre syndrome (MTS) is a hereditary genodermatosis associated with internal malignancies. METHODS: We report the histological case of an atypical sebaceous gland adenoma of the palpebral conjunctiva in a 42-year-old female patient. RESULTS: The combination of this adenoma with atypical adenomatous hyperplasia of the endometrium and a strong family history of gastrointestinal and urogenital cancers led to the diagnosis of MTS. CONCLUSION: We present a case where the diagnosis of an atypical solitary sebaceous gland adenoma of the palpebral conjunctiva combined with a conspicuous personal and family history led to the diagnosis of MTS. PMID- 7890188 TI - Binocular interactions and steady-state VEPs. A study in normal and defective binocular vision (Part II). AB - BACKGROUND: Recent evidence indicates that an index of binocular activity may be found in some properties of steady-state visual evoked potentials (VEPs), such as amplitude facilitation and phase shortening. We evaluated binocular interactions with steady-state VEPs in normal subjects as well as in patients with concomitant strabismus and defective binocular vision. METHODS: Steady-state (8-Hz) VEPs to counterphased sinusoidal gratings (1.2 c/deg spatial frequency) of low contrast (3.2%) were recorded in 19 esotropic patients and in 18 age-matched controls. Patients had either anomalous retinal correspondence (ARC, n = 10) or suppression (n = 9) in casual seeing conditions (striated glasses). In all subjects, both binocular and monocular VEPs displayed a major component at twice the stimulation frequency (second harmonic), whose amplitude and phase were measured. A binocular interaction index was obtained by comparing binocular VEPs (BVEPs) with the sum (vectorial) of the two monocular VEPs (SMVEPs). RESULTS: In normal subjects, BVEPs were larger in amplitude than SMVEPs (facilitation), and shortened in latency (phase). On average, both ARC and suppression patients displayed loss in amplitude facilitation and absence of phase shortening. However, 50% of ARC patients showed clear VEP facilitation. In both ARC and suppression patients, the amplitude ratio BVEP/SMVEP was negatively correlated with the amount of the angle of deviation. CONCLUSION: These results suggest that losses in amplitude facilitation and phase shortening of binocular steady-state VEPs reflect abnormal binocular interactions associated with different forms of sensorial adaptation in concomitant strabismus. PMID- 7890190 TI - The influence of the cutting procedure on the loss of corneal endothelial cells of the recipient eye in mechanically guided trephination. AB - BACKGROUND: Excessive damage to the endothelial monolayer during corneal trephination may contribute to transplant failure. For this reason, we performed several trephining experiments to determine the influence of various cutting conditions (sharpness, rotation rate, and cutting power) on the endothelial damage in the recipient bed. METHODS: A mechanically guided motor trephine (Mikro Keratron) was used for cutting experiments in fresh, enucleated porcine eyes. Eight different, reproducible combinations of cutting conditions were applied, and ten epithelial, full-thickness trephinations were performed for each combination. The endothelial defect was measured with a light microscope (60 x). In addition, the bend radii of the porcine cornea were measured. RESULTS: The mechanically guided Mikro-Keratron used with a sharp blade, high rotation rate (840 rev/min), and moderate cutting power (49 mN) caused a 31-micron-wide band of damaged endothelium in the recipient bed. Decrease of the rotation rate to 30 rev/min resulted in an increase of the endothelial defect to 168%. A cutting power of 392 mN combined with a rotation rate of 840 rev/min increased the defect to 126%. The system allowed full-thickness 360 degrees trephination. The corneal bend radii in porcine eyes measured 8.28 mm horizontally and 8.20 mm vertically. CONCLUSION: Our preliminary results indicate that the mechanically guided motor trephine, used under optimal conditions, is a suitable cutting device and may improve the outcome of penetrating keratoplasty; however, further investigation of this new approach is necessary. PMID- 7890189 TI - Effects of high intraocular pressure on the glucose metabolism in the retina and optic nerve in old atherosclerotic monkeys. AB - BACKGROUND: There are reasons to suspect that in patients with high intraocular pressure and glaucoma, there is underperfusion of the intraocular tissues and optic nerve head, leading to tissue hypoxia and neuronal damage. Studies in young, healthy monkeys have demonstrated that there is efficient autoregulation of the blood flow, and essentially normal glucose consumption, even at very high intraocular pressures that reduce the perfusion pressure to levels around 30 mm Hg. It seemed likely that the conditions might be different in old monkeys that had been on atherogenic diet for long periods of time and that such monkeys were a better model for glaucomatous patients. METHODS: The perfusion pressure in one eye was reduced to 30-35 mmHg in four old rhesus monkeys that had been on atherogenic diet for 12.5 years, and the glucose consumption in the eyes and optic nerves was studied with the 14C-2-deoxyglucose (2DG) method of Sokoloff et al. RESULTS: There was enhanced uptake of 2DG in the inner as well as outer parts of the retina and in the optic nerve head in all four monkeys studied, indicating compromised supply of oxygen resulting in anaerobic glycolysis. CONCLUSION: Old monkeys that have been on atherogenic diet seem more susceptible to elevation of the intraocular pressure than young, healthy monkeys, thereby suggesting defective autoregulation in them. Such differences in susceptibility may play a role also in the development of ischemic disorders of the optic nerve head and glaucomatous optic neuropathy. PMID- 7890191 TI - Localized retinal nerve fiber layer defects in nonglaucomatous optic nerve atrophy. PMID- 7890192 TI - Optic disc hemorrhages after ocular contusion. PMID- 7890193 TI - A case study of sibling relationship in sarcoidosis by HLA-DNA genotyping. PMID- 7890194 TI - Expenditure patterns by age and income among mature adults: does age matter? AB - Using data from the 1984-85 Consumer Expenditure Survey (CES), we examined how expenditure patterns of elderly persons (aged 65-74 and 75 and over) at different income-to-needs levels differ from those of younger mature adults (aged 45-54 and 55-64) at similar income-to-needs levels. Patterns of spending are examined in a variety of areas within three domains--giving, recreation, and essentials. Several important differences exist in the ways that households headed by persons of different ages allocate their expenditures in the domains of essentials and recreation, but few differences exist in the domain of giving. Consistent income group differences exist in expenditure patterns across virtually every area within the three domains. Both age and income differences remain significant when multivariate analyses are performed; thus, the story told is one in which both age and income play important roles. PMID- 7890195 TI - Evaluating Alzheimer's special care units: reviewing the evidence and identifying potential sources of study bias. AB - Special Care Units (SCUs) for Alzheimer's disease have been proliferating in long term care, but their effectiveness remains unproven. This review summarizes the published studies, presents and discusses the many potential sources of bias that pose special problems for SCU research, and proposes strategies for conducting and interpreting future outcome studies in this difficult research setting. PMID- 7890196 TI - Understanding ageism: lessons from feminism and postmodernism. AB - I argue that ageism is a set of oppressive social relations directed at and constructed in images of the aged body. Drawing from feminist and postmodern theorists I suggest that we must avoid essentialism, be sensitive to historical and geographical variations in the form of ageism, focus on the contested nature of the aged body and associated identities, and reject attempts at universalizing scholarship. I suggest that our work focus on five sites of struggle around ageist identities: the labor force, the household, popular culture, the state, and the built environment, each of which is involved in the construction and reconstruction of the aged body. PMID- 7890197 TI - Recounts of elderly deaths: endorsements for the Patient Self-Determination Act. AB - Circumstances in the last 3 days of life were examined for a sample of 1,227 elderly decedents in Fairfield County, Connecticut, in 1985. Interviews were with a surviving next-of-kin or a nonrelative about 3 months after the event of death. Most decedents were in a hospital or a nursing home the night before death (45% and 24%, respectively). In the days preceding death, about 34% of the decedents knew that death was impending and about 40% had difficulty recognizing family members. These and other findings support the need for elderly people to complete advance directives. PMID- 7890198 TI - Developing and testing outreach materials on Alzheimer's disease for Asian and Pacific Islander Americans. AB - Compared to whites, minorities have similar rates of dementia but are less likely to use services. Native language videos and brochures that incorporated culturally specific perceptions of dementia, caregiving, and help-seeking for seven Asian and Pacific Islander American (APIA) groups were developed and tested. Findings suggested that these tools were culturally appropriate and, when used in combination with discussion, helped increase awareness of Alzheimer's disease and sources of help. PMID- 7890199 TI - The effects of visual barriers on exiting behavior in a dementia care unit. AB - Exiting due to wandering was a problem for caregivers in this dementia care unit. Previous attempts to control exiting by wanderers proved ineffective. We manipulated the view and light through a window using visual barriers: window blind, cloth barrier, and a combination of the two. The closed blind reduced exiting by 44%. The cloth barrier was the most effective solution, reducing exiting by 96%. The combination of the blind and cloth barrier reduced exiting 88%. These findings support those of Namazi, Rosner, and Calkins (1989). PMID- 7890200 TI - Should intrastate funding formulae for the Older Americans Act include a rural factor? AB - Most states maintain an Intrastate Funding Formula (IFF) to allocate Older Americans Act funds to planning and service areas within their state. The intention of these formulae is to target resources to those elders in the greatest economic and social need. To achieve this objective, the vast majority of states include measures of age, income, and race in their IFFs. In contrast, the inclusion of a geographic or rural factor is much more controversial. This research was initiated to determine if there was empirical support for the argument that residence influences the need for services after controlling for those factors commonly used by most states in their IFFs. Using data from the Supplement on Aging to the 1984 National Health Interview Survey, the results demonstrate that residing in a nonmetropolitan area increases the likelihood of poor health and the need for services after controlling for age, income, and race. Results also indicate that collectively the four predictor variables account for a very small proportion of the variance in need. PMID- 7890201 TI - Nursing home residents at risk of hospitalization and the characteristics of their hospital stays. AB - Little national data have been available to guide the design of programs aimed at reducing the hospitalization of nursing home residents. This article uses the 1987 National Medical Expenditure Survey to identify elderly nursing home residents with an elevated risk of hospitalization and the reasons for and outcomes of residents' hospital stays. Study findings include an elevated risk of hospitalization for residents with one of several different primary diagnoses and a rise in risk as ADL dependence increases. An infection was the main medical reason for roughly 27% of hospital stays. The results suggest possible target groups for two types of programs aimed at reducing hospitalization. PMID- 7890202 TI - Predictors of nursing home residents' participation in activity programs. AB - Nursing homes are mandated by the Omnibus Budget Reconciliation Act (OBRA) to provide activity programs (U.S. Congress, 1987). Little information exists, however, as to residents' participation in activity programs. Using data from a Health Care Financing Administration project, the present study examines the relationship between resident characteristics and time participating in activities. Among 2,672 nursing home residents we found measures of resource use, cognitive abilities, depression, sense of initiative/involvement, activity repertoire, location preferences, and gender all to be significant in explaining the amount of activity time. PMID- 7890203 TI - The marital perceptions of elderly persons living or having a spouse living in a long-term care institution in Canada. AB - The focus of this study is on the way that older married persons living, or having a spouse living, in a long-term care institution perceive their marriages following relocation. A qualitative analysis of 161 interviews was conducted. For noninstitutionalized spouses (n = 74), four themes emerged from the data- "marriage as a memory," the "illusory marriage," the "changed marriage," and the "continuing marriage." For institutionalized spouses (n = 87), three themes emerged, including the "happy marriage," the "detached marriage," and the "altered marriage." Relocation did not appear to have a direct impact on the way respondents perceived their marriages. Continuity theory was helpful in understanding these marital perceptions. PMID- 7890204 TI - Medical services in social HMOs: a reply to Harrington et al. PMID- 7890205 TI - A standardized patient program in a mandatory geriatrics clerkship for medical students. AB - This article describes the development and implementation of a new standardized patient program in a required geriatrics clinical clerkship for fourth-year medical students. A student survey was also conducted to provide evaluations of the program and to determine the frequency with which students' clinical skills are directly evaluated by faculty. Thirty-six percent reported never having been observed while obtaining a history and 24% having been observed only once; 26% had never been observed while completing a physical examination and 39% had been observed only once. The implementation of a standardized patient program provided students with direct feedback on their clinical skills and was rated positively, (good, very good, or outstanding) by 76% of the students. PMID- 7890206 TI - The impact of respite use on nursing home placement. AB - The results of experimental studies of the effects of respite care have been difficult to interpret because researchers have lacked experimental control over who actually received the treatment. Data from one such study are reanalyzed, focusing on the linear relationship between amount of respite use and probability of nursing home placement at the end of the treatment period. The results indicate a significant negative relationship between amount of respite use and nursing home placement. PMID- 7890207 TI - Marital status of caregiving daughters and co-residence with dependent parents. AB - The role of caregiving daughters' marital status is examined as it relates to their sharing households with disabled elderly parents. Married daughters fared best in well-being, income, and social support. Never-married women were the most likely to have never moved out of the parental home. Separated/divorced caregivers, more than the married and widowed, had moved into the parent's home rather than the reverse and widowed daughters had lived in re-formed joint households longest. The main reason for re-forming shared households was disability of the parent. Among other reasons were death or withdrawal of previous caregiver and financial problems, with separated/divorced daughters the most likely to mention finances. PMID- 7890208 TI - Caring for frail elderly parents: a comparison of adult sons and daughters. AB - This research examines the impact of various factors on perceived emotional strain of adult son and daughter caregivers of frail elderly parents. Daughters experienced higher levels of emotional strain than did sons. Perceived interference between caregiving and the caregiver's personal and social life predicted emotional strain for both sons and daughters. For daughters the most important predictors of emotional strain were interference with work and quality of relationship with the parent. For sons the most important predictors were behavioral problems of the parent and few informal helpers. PMID- 7890209 TI - The impact of chronic illness on the health and well-being of family members. AB - Examined is the impact of dementia on the physical and mental health of all family members caring for an ill parent/spouse. The sample included 97 spouses of patients diagnosed with either Alzheimer's disease or vascular dementia, 186 offspring, and 97 offspring spouses or "in-laws." Multiple regression tested the association between severity of the illness and family member health and well being. Severity was significantly associated with health and well-being for spouses, offspring, and in-laws, regardless of the amount of caregiving, demonstrating the potential cascading effect of the illness through the family. Use of services displayed no direct association with spouse health and well being, but service utilization interacted with illness severity. The relationship between severity of illness and spouse health was lower under conditions of high service utilization than under conditions of low service utilization. PMID- 7890210 TI - Why portal hypertensive varices bleed and bleed: a hypothesis. AB - Continued bleeding or early rebleeding is associated with a poor prognosis in patients with variceal haemorrhage. It is not clear why bleeding stops in some patients and continues or restarts in others. It is suggested that secondary haemodynamic changes in the splanchnic circulation after a bleed may contribute to the risk of further bleeding. These changes include the effects of hypotension on portocollateral resistance, the effects of blood in the gut on splanchnic blood flow, and the effects of blood volume expansion on portal venous pressure during resuscitation. These factors, working in concert, cause a secondary rise in portal venous pressure, which may precipitate further bleeding. Treatment aimed at preventing these secondary haemodynamic changes may be beneficial. It is probable that somatostatin and octreotide could act in this way, which may explain their therapeutic efficacy. PMID- 7890211 TI - Portal and systemic haemodynamic response to acute and chronic administration of low and high dose isosorbide-5-mononitrate in patients with cirrhosis. AB - Oral isosorbide-5-mononitrate (Is-5-Mn) was given in doses of 10 and 40 mg acutely and chronically (twice daily for four weeks), allowing a nitrate free interval to 25 patients with cirrhosis. Both 10 mg and 40 mg Is-5-Mn reduced the hepatic venous pressure gradient acutely and chronically, without evidence of tolerance. This was achieved by a reduction in the wedged hepatic venous pressure. The effect on mean azygos blood flow was variable with no significant mean change seen acutely or after chronic use with either dose. The variability was dependent not on the dose used but on the initial azygos flow; the flow in patients with initially low values increased and those with high azygos flows decreased after nitrate challenge. The development of the porto-collateral flow seems an important parameter in predicting haemodynamic response to Is-5-Mn. PMID- 7890212 TI - Energy expenditure and substrate metabolism in patients with cirrhosis of the liver: effects of the pattern of food intake. AB - Patients with liver cirrhosis are often undernourished. In healthy subjects, the pattern of food intake is one of the variables that can influence energy balance and substrate metabolism. The short term (two day) effect of the pattern of food intake in patients with cirrhosis and controls was compared. In a respiration chamber, eight patients with cirrhosis of the liver and 23 controls were fed to estimated energy balance in two meals daily ('gorging' pattern) and four to seven meals daily ('nibbling' pattern). Twenty four hour energy expenditure, expressed as a multiple of the sleeping metabolic rate, was reduced in patients with cirrhosis (1.31 (0.03) v 1.44 (0.02) for controls; p < 0.01) because of an increased sleeping metabolic rate per kg fat free mass in these patients. In both patients and controls, the respiratory quotient was significantly lower during the morning preprandial period (9.00-12.00) on the gorging pattern, reflecting a higher oxidation ratio of fat to carbohydrate compatible with a more catabolic state. For patients with cirrhosis, a nibbling pattern of food intake, including a good breakfast and a late evening meal, would be preferable, in order to have shorter episodes of catabolism during the day. PMID- 7890213 TI - Increased serum pancreatitis associated protein (PAP) concentration after longterm alcohol consumption: further evidence for regular subclinical pancreatic damage after heavy drinking? AB - It has been shown recently that longterm but not short term heavy drinking of alcohol frequently results in increased serum activities of pancreatic enzymes suggesting subclinical pancreatic injury. Serum pancreatitis associated protein (PAP) is a novel protein, whose synthesis in the acinar cells and release into serum is specifically induced by acute pancreatic damage. This study was performed to further characterise the alcohol induced subclinical pancreatic injury by using serum PAP measurements. Three groups were studied: (1) control group (n = 25), (2) short term drinking group (n = 20), who consumed 2.0 g of ethanol per kg body weight during four hours, and (3) longterm drinking group (n = 32), who were admitted to withdrawal clinic after a median 30 months heavy drinking period. Serum PAP concentration was low in the control group (8 (5 to 12) micrograms/l, geometric mean (95% confidence intervals)). In the short term drinking group serum PAP was in the range of the control group values during 56 hours after drinking. Longterm drinking induced at least a 10-fold increase in serum PAP, the highest concentrations being seen on day 2 after drinking had ended (106 (61 to 184) micrograms/l). The patients did not develop abdominal symptoms, increased blood white cell count, or increased serum C reactive protein concentration. These results further support the suggestion that heavy longterm drinking often induces subclinical pancreatic damage, but not clinical pancreatitis. PMID- 7890214 TI - Changes in the intragastric distribution of Helicobacter pylori during treatment with omeprazole. AB - Omeprazole is a powerful inhibitor of gastric acid and may suppress Helicobacter pylori by effecting the pKa of H pylori urease, by altering the pattern of infection, or by promoting overgrowth of other bacteria. At routine endoscopy H pylori was detected by histology and culture before and after four weeks' treatment with omeprazole, 40 mg each morning. A 13C-urea breath test was also done at t = 0, 2, 4, and 6 weeks. Thirty nine patients with duodenal ulcer (n = 25) or reflux oesophagitis (n = 14) were studied, of whom 29 of 39 had H pylori infection. During omeprazole treatment, 13C-urea breath test values fell significantly--mean (SEM) values before treatment and at four weeks were 23.0 (2.1) and 15.5 (2.7) per mil respectively, p < 0.001. Before treatment H pylori was seen in 28 of 29 antral, 29 of 29 corpus, and 28 of 29 fundic biopsy specimens. After four weeks of omeprazole treatment, the histological density of H pylori in the antrum and corpus was reduced (p < 0.001), while that in the fundus was increased. The migration of H pylori from the antrum to the fundus was associated with a corresponding decrease in the activity of antral gastritis. H pylori was not seen in antral biopsy specimens from 12 of 29 patients whose median excess delta 13CO2 excretion fell from 23.0 to 9.9 per mil. In the body mucosa, 26 of 29 specimens were still positive for H pylori and there was no significant change in the gastritis type. Two weeks after finishing treatment, the mean (SEM) excess delta 13CO2 excretion returned to levels before treatment. Omeprazole decreases antral H pylori colonisation but increases that in the fundus. The changes in the intragastric distribution of the organism are associated with concomitant changes in the activity of gastritis and are matched by a progressive fall in the excretion of delta 13CO2. PMID- 7890215 TI - Deoxycholic acid in gall bladder bile does not account for the shortened nucleation time in patients with cholesterol gall stones. AB - The relations between the concentration of deoxycholic acid (DCA), the cholesterol saturation index, and the nucleation time in gall bladder bile were measured to determine the role of DCA in bile in the pathogenesis of cholesterol gall stone disease. Bile was obtained from patients with cholesterol gall stones (n = 30), subjects without gall stones (n = 35), and patients with pigment gall stones (n = 9). Three of 30 cholesterol gall stone patients and 10 of 35 gall stone free subjects were treated with antibiotics by mouth to decrease the concentration of bile DCA and determine the effect of DCA on biliary lithogenecity. Both the percentage and concentration of DCA in bile were similar in patients with and without cholesterol gall stones despite significant differences in their cholesterol saturation indices and nucleation times. Neither the percentage nor the concentration of DCA in bile correlated with either the cholesterol saturation index or the nucleation time. Analysis of subgroups with matching cholesterol saturation indices showed no correlation between the proportion of DCA in the bile and the cholesterol nucleation time. The proportion of DCA in bile was decreased by antibiotic treatment, but this had no effect on the cholesterol saturation index or nucleation time. These results suggest that DCA in bile is not responsible for biliary cholesterol saturation or cholesterol nucleation time. PMID- 7890217 TI - Pancreatic vascular regulation in chronic pancreatitis in cats. AB - In experimental obstructive chronic pancreatitis the normal hyperaemic response to secretory stimulation is lost, suggesting abnormal vascular regulation. Vascular regulatory mechanisms were investigated by observing the effect of increments in portal pressure on pancreatic blood flow in normal cats and cats with chronic pancreatitis. Normal cats maintained pancreatic blood flow until portal pressure was > 15 mm Hg, after which it decreased. Total vascular resistance decreased until the portal pressure was 15 mm Hg and increased thereafter. These observations suggested that metabolic regulatory mechanisms prevailed while portal pressure was in the physiological range but myogenic mechanisms became dominant during portal hypertension. In chronic pancreatitis the basal pancreatic blood flow was reduced and was inversely proportional to portal pressure. Total vascular resistance increased as portal pressure increased. In chronic pancreatitis myogenic regulatory responses prevailed at all levels of portal pressure. In conclusion, intrinsic regulation of pancreatic blood flow was abnormal in cats with chronic pancreatitis. The loss of the predominance of metabolic regulation over the normal range of portal pressure may partly explain the reduction of pancreatic blood flow in response to secretory stimulation. PMID- 7890216 TI - Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid. AB - Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium. PMID- 7890218 TI - Profound duodenogastric reflux causes pancreatic growth in rats. AB - Although duodenogastric reflux is a physiological event, excessive reflux may be a pathogenetic factor in several diseases of the foregut, including cancer. Long term profound duodenogastric reflux produces pancreatic and gastric tumours in rats. The trophic effect of surgically induced duodenogastric reflux on the pancreas was investigated and the mechanisms involved were examined. Rats with profound reflux from a split gastroenterostomy were compared with sham operated and unoperated controls after two and six weeks. In the six week experiment, one reflux and one sham group were given the cholecystokinin (CCK) receptor antagonist devazepide (25 nmol/kg/h). Duodenogastric reflux caused a significant increase in pancreatic weight, DNA, and plasma CCK and gastrin concentrations at both two and six weeks. Devazepide substantially reduced the pancreatic weight increase after six weeks but did not abolish it completely. CCK and gastrin were not affected by devazepide. These results suggest that CCK is largely responsible for the pancreatic growth induced by reflux but another factor may also be involved. The trophic effect of duodenogastric reflux may contribute to the increased incidence of pancreatic cancer reported after gastric surgery. PMID- 7890219 TI - Hepatic venous outflow obstruction in patients with polycystic liver disease: pathogenesis and treatment. AB - Polycystic liver disease is commonly asymptomatic but may present with hepatomegaly, abdominal distension, and dull abdominal pain. Transudative ascites is a rare manifestation in these patients but may occur when portal hypertension is present resulting from associated hepatic fibrosis or after deroofing procedure of a cyst. Exudative ascites might suggest hepatic venous outflow obstruction. Four cases are described where hepatic venous outflow obstruction occurred in patients with polycystic liver disease. Three patients had orthotopic liver transplantation and one had a mesocaval shunt. Of the two patients that survived orthotopic liver transplantation both have shown considerable improvement in their symptoms. None of the patients had any confirmed procoagulant disorder. The mechanism of hepatic venous outflow obstruction in these patients seems to be mechanical compression of hepatic veins by the cysts and associated formation of thrombi in small hepatic vein tributaries. Patients with severe polycystic kidney/liver disease are at risk of hepatic venous outflow obstruction and the onset of this complication is heralded by tender hepatomegaly and presence of exudative ascites. PMID- 7890220 TI - Hepatitis induced by traditional Chinese herbs; possible toxic components. AB - Traditional Chinese herbal remedies are widely available in the United Kingdom for the treatment of chronic skin disorders. Their benefits are considerable, but their use is completely unregulated. Two patients are described here who suffered an acute hepatitic illness related to taking traditional Chinese herbs. Both recovered fully. The mixtures that they took included two plant components also contained within the mixture taken by a previously reported patient who suffered fatal hepatic necrosis. These cases high-light the need for greater awareness of both the therapeutic and toxic potential of herbal remedies, as well as greater control of their use. PMID- 7890221 TI - Acute hepatitis C infection after sexual exposure. AB - A case is described of a woman with acute hepatitis C infection whose partner had chronic hepatitis C infection and where heterosexual contact was the only major risk factor. Infection of both partners was confirmed serologically and by the finding of virus RNA by reverse transcription and polymerase chain reaction amplification. Nucleotide sequence analysis of the NS5 region (RNA polymerase) was used to show that both partners were infected with virus of the same genotype (1a). The nucleotide sequence of virus RNA found in the female patient is closest to variants cocirculating in the male contact, consistent with transmission having occurred between the two. PMID- 7890222 TI - Markers to study human colonic cell proliferation. PMID- 7890223 TI - Duodenal ulcer, gastric acid, and Helicobacter pylori. PMID- 7890224 TI - Cancer of the oesophagus. PMID- 7890225 TI - Current concepts in metastasis. PMID- 7890226 TI - NSAIDs and the chemoprevention of colon and oesophageal cancer. PMID- 7890227 TI - Acid and gastric metaplasia in the duodenum. PMID- 7890228 TI - Pathogenesis of bacterial colitis. PMID- 7890229 TI - Unethical research relating to Helicobacter pylori? PMID- 7890230 TI - Effect of predigested fat on intestinal stimulation of plasma cholecystokinin and gall bladder motility in coeliac disease. AB - Cholecystokinin (CCK) release and gall bladder emptying in response to a fatty meal are completely abolished in coeliac disease. To determine the effect of lipid digestion on CCK release and gall bladder motility, six patients with untreated coeliac disease and a flat jejunal mucosa were studied on two separate days. After an overnight fast, the plasma CCK concentration and gall bladder volume were measured before and at regular intervals after the intraduodenal instillation of 60 ml corn oil (triglycerides) incubated with 40 ml saline or with 40 ml bile and pancreatic juice. The mean (SEM) concentration of free fatty acids in the aqueous phase of corn oil after incubation with bile and pancreatic juice (predigested corn oil) was 78 (35) mM compared with 0.1 (0.1) mM in the aqueous phase of corn oil incubated with saline (undigested corn oil). Integrated plasma CCK in response to predigested corn oil was significantly greater than that in response to undigested corn oil (101 (18) pM. 80 min v-2 (9) pM.80 min; p < 0.005). Similarly, integrated gall bladder contraction in response to predigested corn oil was significantly larger than that after undigested corn oil (817 (210) ml. 80 min v-225 (243) ml. 80 min; p < 0.05). In contrast to undigested corn oil, corn oil that has been predigested with bile and pancreatic juice induces plasma CCK secretion and gall bladder contraction in patients with untreated coeliac disease, presumably by generating and rendering soluble lipolytic products. PMID- 7890231 TI - Analysis of crypt cell proliferation in coeliac disease using MI-B1 antibody shows an increase in growth fraction. AB - This study aimed to investigate the pattern of cellular proliferation and to calculate the growth fraction of small intestinal crypts in 24 patients--eight with untreated coeliac disease (CD), six with treated CD, and 10 controls with normal villous architecture. Duodenal biopsy specimens were stained with MI-B1 antibody using an immunoperoxidase method. Positive stained crypt cells were counted and their position within each intact crypt column was noted. These were used to construct proliferation index distribution curves for each cell position from which the crypt growth fraction for each group of patients was calculated. The crypt growth fraction was found to be higher in the untreated CD group (0.57) than in the treated patients (0.39) and the controls (0.44). The mean (SEM) proliferative index for each crypt was significantly higher in the untreated group (42.3 (10.8)%; p < 0.05) than in the treated CD (21.7 (8.5)%) and control (19.7 (7.5)%) groups and correlated closely with the surface:volume index and enterocyte cell height measurements in all three groups. An increased growth fraction may contribute to other changes in crypt cell kinetics to produce the histological changes seen in untreated CD. PMID- 7890232 TI - Studies on the expression of intestinal lactase in different individuals. AB - Sixty one duodenal biopsy specimens were examined for the expression of lactase at the level of enzyme activity, protein, and messenger RNA. Of the 51 samples with normal villous architecture, 39 were lactase persistent, 11 were nonpersistent (adult type hypolactasia), and one was of indeterminate status. All the lactase persistent individuals showed high mRNA and a high level of the lactase protein as detected by sodium dodecyl sulphate polyacrylamide gel electrophoresis. All the 11 non-persistent individuals tested showed a low level of lactase protein. Nine of the 10 samples tested showed low mRNA and one high mRNA. These results suggest that the lactase persistence polymorphism is controlled at the level of the expression of the lactase gene, though there may be some heterogeneity of the lactase non-persistence phenotype. PMID- 7890233 TI - Effect of cholecystokinin on lower oesophageal sphincter pressure and transient lower oesophageal sphincter relaxations in humans. AB - The effect of cholecystokinin (CCK) on the lower oesophageal sphincter (LOS) pressure, frequency of transient LOS relaxations, and the number of reflux episodes was investigated in six healthy subjects. LOS pressure was recorded on four separate occasions during continuous intravenous infusion of either saline or CCK-33 in doses of 0.25, 0.5, or 1.0 Ivy Dog units per kg body weight per hour (IDU.kg-1.h-1) for 90 minutes. Plasma CCK concentrations did not change during saline infusion, but increased significantly from 2.5 (0.3) pmol/l to steady state levels of 4.0 (0.4) pmol/l, 6.1 (0.4) pmol/l, and 9.3 (0.9) pmol/l respectively starting from 30 minutes. LOS pressure did not change significantly during infusion of saline or of CCK-33 at doses of 0.25 or 0.5 IDU.kg-1.h-1. However, a significant (p < 0.05) reduction in LOS pressure to a minimum level of 12 (4) mm Hg at 30 minutes compared with basal level (18 (4) mm Hg) and compared with saline was observed during infusion of CCK-33 at a dose of 1.0 IDU.kg-1.h-1. In addition, oesophageal motility and pH were recorded simultaneously in these six subjects on two separate occasions one hour before (fasting) and three hours during administration of a gastric load (dextrose 5%, pH 3) combined with continuous intravenous infusion of saline or CCK-33 at a dose of 1.0 IDU,kg-1.h 1. Plasma CCK concentrations did not change during the gastric load combined with saline, but increased significantly to a steady state level of 10.8 (0.8) pmol/l during intravenous infusion of CCK. The number of transient LOS relaxations increased significantly in the first hour during administration of the gastric load compared with fasting levels, both during saline infusion (fasting: 1.7 (0.6)/h, 1st hour: 4.3 (1.2)/h) and during CCK infusion (fasting: 1.7 (0.5)/h, 1st hour: 3.8 (0.7)/h). In the second and third hours the number of transient LOS relaxations fell to fasting levels in both experiments. No significant differences were observed in the number and type of transient LOS relaxations, mechanism of gastro-oesophageal reflux, or duration of acid exposure between the two experiments. It is concluded that in healthy subjects infusion of CCK-33 in a dose of 1.0 IDU.kg-1.h-1 significantly reduces LOS pressure but does not affect the frequency of transient LOS relaxations or acid exposure time during a continuous liquid gastric load. PMID- 7890234 TI - Soluble interleukin-6 receptors in inflammatory bowel disease: relation to circulating interleukin-6. AB - The in vivo appearance of soluble interleukin (IL)-6 receptor (sIL-6R) in serum from patients with inflammatory bowel disease was examined using an enzyme linked immunosorbent assay (ELISA). The serum sIL-6R concentrations in patients with active disease (ulcerative colitis, 148.4 (5.1); Crohn's disease, 142.3 (9.3) ng/ml; mean (SEM)) were significantly raised compared with those in patients with inactive disease (ulcerative colitis, 116.2 (7.2); Crohn's disease, 114.3 (7.1) ng/ml), some other type of colitis (104.8 (11.6) ng/ml), or in normal subjects (107.3 (2.4) ng/ml). These differences were also seen in paired samples examined during both active and inactive phases. Additionally, serum sIL-6R and IL-6 concentrations correlated significantly with C-reactive protein levels in both ulcerative colitis and Crohn's disease patients (r = 0.23 and 0.56, respectively; p < 0.05 for both). Furthermore, gel filtration analysis of serum from these patients showed two major peaks of immunoreactive IL-6-one peak corresponding to free IL-6 and another peak to sIL-6R-bound IL-6-this was further confirmed by a luminescence sandwich ELISA. These results, together with its in vitro effects, indicate that natural sIL-6R may function as a powerful enhancer of the IL-6 dependent immune processes observed in inflammatory bowel disease. PMID- 7890235 TI - Platelet dysfunction: a new dimension in inflammatory bowel disease. PMID- 7890236 TI - DNA flow cytometric evaluation of cell cycle distribution in ulcerative colitis: a proposed method for assessing severity of disease. AB - The assessment of disease severity in ulcerative colitis depends mainly on subjective variables, and an objective method of assessing mucosal inflammation is needed. Determination of the synthetic phase of the cell cycle is an accurate expression of inflammatory activity in the colonic mucosa. The aim of the study was to find out if the proliferative index or the synthetic phase (S phase) of the colonic mucosa of patients with ulcerative colitis, as evaluated by DNA flow cytometry, is a reliable and reproducible marker of disease activity. Sixty consecutive patients with ulcerative colitis of different degrees of activity were entered into the study and submitted to colonoscopy plus multiple rectal biopsies. Disease severity was defined for each patient by means of a clinical, endoscopic, and histological score. Flow cytometry was used to calculate the proliferative index and the S phase of the cell cycle. A statistically significant correlation (p < 0.001) was found between all indices of severity. It is suggested that flow cytometric evaluation of the cell cycle in the rectal mucosa may be an efficient method of assessing severity of disease and efficacy of medical treatment in ulcerative colitis. PMID- 7890237 TI - Selective inhibition of fatty acid oxidation in colonocytes by ibuprofen: a cause of colitis? AB - Ibuprofen is associated with initiation or exacerbation of ulcerative colitis. As ibuprofen selectively inhibited fatty acid oxidation in the liver or caused mitochondrial damage in intestinal cells, its effect on substrate oxidation by isolated colonocytes of man and rat was examined. Ibuprofen dose dependently (2.0 7.5 mmol/l) and selectively inhibited 14CO2 production from labelled n-butyrate in colonocytes from the proximal and distal human colon (n = 12, p = < 0.001). Glucose oxidation was either unaltered or increased. Because short chain fatty acid oxidation is the main source of acetyl-CoA for long chain fatty acid synthesis, the inhibition of prostaglandin synthesis by ibuprofen in the colonic mucosa could also occur at this level. Because the concentrations of ibuprofen that can be attained in the human colon are not known, conclusions drawn from current dosages are tentative. The inhibition of fatty acid oxidation by ibuprofen may be biochemically implicated in the initiation and exacerbation of ulcerative colitis, manifestation of which would depend on the ibuprofen concentrations reached in the colon. PMID- 7890238 TI - Controlled trial of oligopeptide versus amino acid diet in treatment of active Crohn's disease. AB - Elemental diets are effective in inducing remission in active Crohn's disease, but how they exert this therapeutic effect is unclear. In a previous study a whole protein containing diet proved less effective than one in which food antigens were excluded, suggesting that exclusion of food antigens from the gut was a possible mechanism. This study was designed to test whether an oligopeptide diet of hydrolysed proteins was as effective as an amino acid based diet. These diets were equally antigen free but with different nitrogen sources. Forty four patients with active Crohn's disease were randomised in a controlled trial of amino acid versus oligopeptide diet. The feeds were given by nasogastric tube in equicaloric quantities and were the sole form of nutrition. Treatment was continued for four weeks although failure to improve by day 10 resulted in withdrawal. Quantitative leucocyte scintigraphy was used to investigate the effect of diet treatment on gut inflammation. Clinical and nutritional responses to treatment were also measured. Sixteen patients entered remission (including withdrawal of corticosteroids), six patients could not tolerate the nasogastric tube, and 22 patients failed to respond. The two diets were equally effective. Patients who responded had a rapid drop in clinical index of disease activity and a major reduction in the bowel uptake of leucocytes on scintigraphy. The oligopeptide and amino acid based enteral feeds were equally effective at inducing remission in active Crohn's disease. With both diets clinical improvement was accompanied by a reduction in intestinal inflammation. PMID- 7890239 TI - Photosensitisation and photodynamic therapy of oesophageal, duodenal, and colorectal tumours using 5 aminolaevulinic acid induced protoporphyrin IX--a pilot study. AB - The first study of photodynamic therapy in the human gastrointestinal tract using 5 aminolaevulinic acid (ALA) induced protoporphyrin IX as the photosensitising agent is described. Eighteen patients with colorectal, duodenal, and oesophageal tumours were studied. After 30-60 mg/kg of ALA given orally, biopsy specimens of tumour and adjacent normal mucosa were taken 1-72 hours later. These specimens were examined by quantitative fluorescence microscopy for assessment of sensitisation with protoporphyrin IX. Ten patients were given a second dose of ALA a few weeks later and their tumours were treated with red laser light (628 nm). With 30 mg/kg ALA, the highest fluorescence values were detected in the duodenum and oesophagus, and the lowest in the large bowel. Doubling the ALA dose in patients with colorectal tumours gave protoporphyrin IX fluorescence intensities similar to those in patients with upper gastrointestinal lesions and improved the tumour:normal mucosa protoporphyrin IX sensitisation ratio. The treated patients showed superficial mucosal necrosis in the areas exposed to laser light. Six patients had transient rises in serum aspartate aminotransferases, two mild skin photosensitivity reactions, and five mild nausea and vomiting. In conclusion, photodynamic therapy with systemically administered ALA may be a promising technique for the treatment of small tumours and areas of dysplasia such as in Barrett's oesophagus. PMID- 7890241 TI - Diagnostic value of a guaiac occult blood test and faecal alpha 1-antitrypsin. AB - This study evaluates the diagnostic accuracy of a faecal occult blood test and faecal alpha 1-antitrypsin in the investigation of patients with gastrointestinal symptoms or iron deficiency anaemia. One hundred and seventy nine patients with either iron deficiency anaemia (n = 67), changed bowel habit and aged > 39 years (n = 107), or a history suggestive of melaena (n = 5) provided faecal samples. After investigation, 32 patients had a diagnosis of possible gastrointestinal bleeding and 139 patients had no evidence of gastrointestinal bleeding. Eight patients had a cause of enteric protein loss in the absence of gastrointestinal bleeding and were excluded from subsequent analysis. The faecal alpha 1 antitrypsin test was diagnostically more accurate than the guaiac test in identifying probable gastrointestinal bleeding (82% and 72% respectively, p < 0.05). This faecal alpha 1-antitrypsin test was also more specific (83% and 72% respectively, p < 0.05), but was not significantly more sensitive (78% and 72% respectively). The sensitivity of these tests was insufficient to recommend their use for most patients in this study. PMID- 7890240 TI - Detection of c-Ki-ras mutations in faecal samples from sporadic colorectal cancer patients. AB - Colonic exfoliated epithelial cells in faecal material provide a source of human DNA which has been analysed for the presence of the tumour marker ras, in order to detect early tumour cells. The stool samples were subjected to a preliminary sample preparation step followed by centrifugation. DNA was extracted from both the centrifugation pellet and supernatant fractions, as well as from endoscopy washings, using a conventional phenol chloroform extraction method and was then purified on glass milk or spin columns. The purified DNA was amplified using mitochondrial primers and analysed for ras mutations using a non-radioactive, allele specific mismatch method. Corresponding tumour DNA was analysed for mutations using the same method. The results show that approximately 50% of the faecal samples analysed exhibited the presence of ras mutations which were also observed in the corresponding tumours. A double mutation was detected in one supernatant. Our findings represent an important stage in the development of a diagnostic test for the early detection of colorectal cancer. PMID- 7890242 TI - Surgical emergencies in tropical gastroenterology. PMID- 7890243 TI - A screening clinic for relatives of patients with colorectal cancer in a district general hospital. AB - A family cancer screening clinic was set up to screen and counsel subjects at above average risk of developing colorectal cancer. Criteria for referral were one first degree relative under 50 years or two of any age with colorectal cancer. Pedigree information was used to estimate lifetime risks of developing colorectal cancer and offer appropriate screening: colonoscopy for high risks (greater than 1 in 10), faecal occult blood testing for lower risks. One hundred and eleven subjects from 76 families were seen over four years. Forty two families gave a pedigree consistent with dominantly inherited non-polyposis colorectal cancer syndrome (HNPCC). Three subjects from one family were found to have familial adenomatous polyposis. Ninety two colonoscopies yielded 21 patients with polyps (12 had tubular adenomas, including one with early malignant invasion). Thirty three per cent (four of 12) of the tubular adenomas were beyond the reach of a flexible sigmoidoscope. Three hundred and forty two further high risk relatives were identified from the family history. PMID- 7890244 TI - Colonic mucin synthesis is increased by sodium butyrate. AB - The effects of sodium butyrate and sodium bromo-octanoate (an inhibitor of beta oxidation) on colonic mucus glycoprotein (mucin) synthesis have been assessed using tissue from colonic resection samples. Epithelial biopsy specimens were incubated for 16 hours in RPMI 1640 with glutamine, supplemented with 10% fetal calf serum and N-acetyl-[3H]-glucosamine ([3H]-Glc NAc), and differing concentrations of sodium butyrate. Incorporation of [3H] Glc NAc into mucin by normal epithelium at least 10 cm distant from colonic cancer was increased in the presence of sodium butyrate in a dose dependent manner, with maximum effect (476%) at a concentration of 0.1 mM (number of specimens = 24 from six patients, p < 0.001). The increase in response to butyrate was not seen when specimens were incubated in the presence of the beta oxidation inhibitor sodium bromo-octanoate 0.05 M. The striking increase in mucin synthesis that results when butyrate is added to standard nutrient medium suggests that this may be an important mechanism affecting the rate of mucin synthesis in vivo and may also explain the therapeutic effect of butyrate in colitis. PMID- 7890245 TI - Eclampsia-like seizures and electroencephalographic changes in pregnant rabbits with endothelin-1 injections. AB - To examine the possible role of endothelin and vasospasm in eclamptic seizures, we studied and analyzed the electroencephalograms (EEG) of endothelin-1 (ET-1) treated pregnant, nonpregnant and sham control (dextrose-treated) rabbits. After multiple intravenous bolus injections of ET-1 (500 pmol/kg) or 5% dextrose in the rabbits, we recorded EEG directly from the brain cortex and analyzed by Fast Fourier Transform (FFT). Water content was measured in the brain of all groups (n = 7). Repeated seizures occurred in all of the pregnant and 2 of the nonpregnant rabbits by variable doses of ET-1. FFT analysis showed remarkable changes in frequency and power arrays characterized by mild to severe form of dysrhythmia, high-voltage spikes, high-voltage fast and slow waves after ET-1 injections. Water content was increased in brain mass in ET-1-treated rabbits (p = 0.001) suggesting an ET-1-induced edema. Histologically we confirmed that ET-1 caused ischemic changes in brain tissues. However, ET-1 induced more pronounced changes in behavior, EEG, brain edema or ischemia in pregnant than in nonpregnant groups. The injections of exogenous ET-1 into the brain substances were strongly suggested by immunohistochemical study with polyclonal antiendothelin antibody in brain tissue sections. Therefore, we assume that endothelin along with other vasoactive substances causes acute cerebral vasospasm and ischemia inducing EEG changes leading to ultimate clinical convulsions in eclampsia. PMID- 7890246 TI - Correlation of placental isoferritin with birth weight and time point of first contractions. AB - In a prospective study, the correlation between serum levels of placental isoferritin (PLF) and outcome of pregnancy was determined in 56 pregnant women. Women with contractions before the 36th week of pregnancy showed significantly lower PLF values compared with women with later contractions (p < 0.01). Furthermore, a strong correlation of PLF levels with birth weight was observed. In 11 (79%) cases with a birth weight < 2,500 g (group A), PLF values were < 10 U/ml whereas only 14% (6 of 42) of women with babies with a birth weight > 2,500 g (group B) revealed PLF levels < 10 U/ml. Because it has been shown previously that PLF has immunosuppressive properties, the secretion of PLF by the placenta could be responsible for the inhibition of the immunoreactivity of the maternal lymphocytes against the embryo. The strong correlation of low PLF values with preterm contractions and/or low birth weight recommends the determination of this protein as a marker for monitoring women with high risk pregnancies. PMID- 7890247 TI - Antenatal bleeding and fetal heart rate. AB - Objective of the paper was to determine the fetal heart rate (FHR) changes that occur in preterm fetuses whose mothers have suffered antepartum bleeding, versus uncomplicated controls. Over a 12-year span, 91 patients with significant antenatal bleeding (bleeding requiring inhospital observation) were examined and compared to 75 controls with uncomplicated normal pregnancies. None of the women were in labor and all were evaluated at 25-37 weeks' gestation. Excluded were: patients with any other complication (i.e., premature rupture of membranes, intrauterine growth retardation, diabetes, hypertension, collagen vascular disease, postuterine surgery, substance abuse and twins). Analysis of the FHR tracings included baseline heart rate, long-term FHR variability, and number and amplitude of FHR accelerations in 20-min segments. There was no difference in baseline heart rate in the preterm fetuses of pregnancies complicated by antepartum bleeding versus controls. However, the parameters associated with FHR reactivity (number of accelerations in 20 min, and amplitude of accelerations) were higher to a statistically significant degree in fetuses of pregnancies complicated by antenatal bleeding than in controls. Fetuses of mothers suffering antenatal bleeding exhibited significant higher rates of reactive FHR patterns at earlier gestational ages than did controls. In conclusion, there is a significant increase in FHR reactivity in pregnancies in which significant antenatal bleeding occurs, suggesting a probable acceleration in fetal central nervous system maturation in these fetuses. PMID- 7890248 TI - Epidural anaesthesia in labour: influence on surgical delivery rates, intrapartum fever and blood loss. AB - We retrospectively analyzed 7,317 fully documented deliveries to assess the effect of epidural anaesthesia (EA) on surgical delivery rates, on the incidence of intrapartum fever and on peripartal blood loss. 1,056 (14.4%) had EA and 6,261 (85.6%) had no or other analgesia. The use of EA was associated with a decreased spontaneous delivery rate (50.0 vs. 79.2%), increased forceps delivery rate (30.7 vs. 4.0%) and increased vacuum extraction rate (3.5 vs. 0.7%). The caesarean section rate was not significantly changed in patients with EA (14.4 vs. 13.0%). Fever greater than 38 degrees C during labour and intrapartum haemorrhage exceeding 500 ml were associated with the use of EA. PMID- 7890249 TI - Continuous pO2 monitoring during dual perfusion of the term human placenta in vitro. AB - A computerized system has been developed to continuously monitor, collect and display pO2 in real time from the maternal and fetal arteries and veins in the dually perfused term placenta. Oxygen electrodes were installed in flow-through chambers in the tubing of the perfusion system. The signal from the O2 electrodes was digitized, acquired, analyzed and displayed in real time during the perfusions using a personal computer. Output from the O2 electrodes was linearly proportional to pO2 (33-502 mm Hg; r2 = 0.99). Running average pO2 values (mean +/- SD) were also calculated for every minute and stored. The captured data files can be recalled and analyzed after completion of the perfusion experiment and compared with other data collected during perfusion. One of the unique capabilities of the pO2 electrodes is their ability to respond rapidly to changing perfusion conditions. For example, as the fetal circulation begins to break down the change is noted before volume loss in the fetal circuit by decreasing fetal vein pO2. PMID- 7890250 TI - Tobacco smoking impairs the local immunosurveillance in the uterine cervix. An immunohistochemical study. AB - Previous reports have supported an association between tobacco smoking and cervical neoplasia. Our observations show an association between smoking and a reduction of the numerical densities of Langerhans cells and of helper/inducer T lymphocytes in the squamous epithelia of the transformation zone of the uterine cervix. This suggests a local impairment of cell-mediated immunity by smoking. This immunosuppressive effect could support the concept that smoking is an independent risk factor for cervical neoplasia. PMID- 7890251 TI - Quantitative analysis of endometrial stromal cells including behavioral changes related to the menstrual cycle in smear specimens. AB - We aimed to obtain quantitative data regarding certain characteristics of stromal cells in smear specimens of normal endometrium, including the cytological changes associated with progression through the menstrual cycle. Eleven histological and 25 cytological specimens of normal endometrium were examined immunochemically using monoclonal antibodies to vimentin and keratin by streptavidin-biotin method. As a result, we decided to use the antibody to vimentin for the differential staining of endometrial smears: cells showing positive staining to vimentin were considered stromal cells. The quantitative nuclear measurements in the smear specimens revealed that the nuclei of endometrial stromal cells were more elongated and had a more dispersed distribution than the glandular cells in the proliferative phase. Although a part of the nuclei of stromal cells became rounder in shape in the secretory phase, they were larger in size than those of glandular cells. PMID- 7890252 TI - Effects of smoking on the levels of antioxidant beta carotene, alpha tocopherol and retinol in human ovarian follicular fluid. AB - The concentrations of beta-carotene, retinol and alpha-tocopherol were measured by high-pressure liquid chromatography in ovarian follicular fluid and plasma samples collected at the time of oocyte recovery from patients enrolled in our in vitro fertilization program. The mean beta-carotene levels in follicular fluid [0.182 +/- (SEM) 0.04 nmol/ml] and plasma (0.37 +/- 0.34 mmol/ml) of smokers (n = 5) were significantly (p < 0.025 and p < 0.001, respectively) lower compared with the mean levels in follicular fluid (0.58 +/- 0.10 nmol/ml) and plasma (1.11 +/- 0.09 mmol/ml) in nonsmokers (n = 11). The follicular fluid and plasma retinol and alpha-tocopherol levels were comparable among the nonsmokers and smokers. These findings direct attention to a possible role of the antioxidant beta-carotene, per se, as a biological marker in ovarian oocyte follicular maturation and function. PMID- 7890253 TI - Effect of acute ethanol ingestion on prolactin in menopausal women using estradiol replacement. AB - Epidemiologic studies suggest that women who consume ethanol are at an increased risk for developing breast cancer. Two randomized, crossover studies were performed to examine the effects of ethanol on prolactin in menopausal women using transdermal estradiol. In study 1, transdermal estradiol patches (0.15 mg) were administered to menopausal women (n = 7) the day before ethanol administration. At 8.00 h, the women ingested ethanol (1 ml/kg, 95% ethanol) or an isocaloric carbohydrate drink. Prolactin levels were measured frequently for 6.3 h. Serum ethanol levels reached a broad peak from 40 to 100 min after initiation of ethanol ingestion. Serum prolactin levels were significantly higher after ethanol ingestion than after the isocaloric carbohydrate drink ingestion (p < 0.03). Study 2 was identical to study 1 except that the transdermal estradiol patches were removed after completion of ethanol or carbohydrate ingestion. In study 2, serum prolactin was greater after ethanol ingestion than after carbohydrate ingestion (p < 0.001). In menopausal women using transdermal estradiol, acute ethanol ingestion is associated with an increase in serum prolactin. PMID- 7890254 TI - Superovulation and intrauterine insemination in the treatment of male factor infertility. AB - Recent studies report that superovulation combined with intrauterine insemination (IUI) is more successful than superovulation alone, IUI alone or superovulation with intracervical insemination in couples with male subfertility. Our study evaluated two superovulation protocols in the management of male factor infertility using IUI: (A) clomiphene citrate and human chorionic gonadotropin (HCG) and (B) human menopausal gonadotropin and HCG. Fifteen couples with severe oligoasthenozoospermia (OAS) were treated with protocol A in 54 cycles, and no pregnancies were achieved. Eight of the 15 couples with severe OAS subsequently received protocol B for 24 cycles and elicited no pregnancies. Thirty-seven couples with moderate OAS received protocol A for 169 cycles, and 2 pregnancies ensued (5.4% per couple and 1.12% per cycle). Twelve of the 35 nonpregnant couples with moderate OAS then received protocol B for 31 cycles, and 4 pregnancies were recorded (33.3% per couple and 12.9% per cycle). PMID- 7890255 TI - Immune response characteristics in women with chlamydial genital tract infection. AB - Immune responses in women with chlamydial genital tract infection who achieved a bacteriologic cure were prospectively compared to those women who had an incomplete clinical response. Local anti-chlamydia IgA antibody responses were significantly diminished in the outpatient treatment group who had an incomplete response, while circulating IgG responses did not differ significantly between groups. This is in contrast to both specific and non-specific lymphoproliferative responses which were similar between uninfected controls and women with a chlamydial genital tract infection, regardless of treatment outcome. Thus, the kinetics of successful outpatient treatment of chlamydial genital tract infections may have an immunologic component which can be measured at the time of initial evaluation, and may be predictive of the clinical response to adjunctive antibiotics. PMID- 7890256 TI - Ritodrine tocolysis and neonatal intraventricular-periventricular hemorrhage. AB - Betamimetic drugs are commonly used for tocolytic therapy. To determine their potential role in periventricular-intraventricular neonatal hemorrhage (IVH), 103 preterm births with cranial ultrasonography results were evaluated for the history of betamimetic therapy. The study group was divided into three subgroups according to the cause of the preterm delivery: 44 patients were accepted as tocolysis failure (group A); 53 patients were too late for tocolysis (group B), and these latter cases were taken as controls for group A; for the remaining 6 patients, tocolysis was contraindicated due to fetomaternal reasons (group C), and these cases were not included in the analysis. In group A, 32 patients got ritodrine, 6 patients got combined therapy including ritodrine plus magnesium sulfate or nifedipine. When cases in group A who got ritodrine only or combined therapy are compared with the no-treatment group, no significant difference in neonatal IVH incidences could be found (p > 0.005). Ritodrine does not appear to affect the incidence of neonatal IVH. PMID- 7890257 TI - Sustained prolactin release associated with precocious ovarian failure. AB - Five women after precocious menopause and 1 patient with primary ovarian failure showed a simultaneous elevation of plasma gonadotropin and prolactin. The hypersecretion of plasma prolactin was still present 6 months after ovarian failure. After 12-18 months of observation while FSH and LH concentration remained elevated, prolactin concentrations normalized in 5 women and decreased in 1. PMID- 7890258 TI - The clinical effect of uterine hyperflexion and cervical elongation in cases of pelviscopic hysterectomy. AB - In a retrospective study of women who had undergone pelviscopic hysterectomies in the last 2 years, we focused on postoperative cyclic spotting. Preoperatively, a regular, cyclic menstruation and a premenopausal sexual hormone constellation were common to all patients. In the first group (n = 29), spotting occurred only in association with two uterine anatomical varieties: uterine hyperflexion and cervical elongation. The second group (n = 18), in which intraoperative internal electrocoagulation of the residual cervical envelope was performed, no spotting occurred despite the presence of uterine hyperflexion and cervical elongation. This procedure prevents the occurrence of postoperative spotting in cases of uterine anatomical varieties. PMID- 7890259 TI - Hypoplastic left heart syndrome: color Doppler sonographic and magnetic resonance imaging features in utero. AB - A 26-year-old Japanese woman, gravida 2, para 1, was referred to our ultrasonography clinic at 27 weeks' gestation, because of a suspected fetal heart anomaly. The hemodynamic examination, specific for hypoplastic left heart syndrome and obtained with color Doppler sonography, gave a clue to an accurate diagnosis of this entity. Moreover, the use of magnetic resonance imaging provided information complementary to the sonographic findings. The sophisticated type of fetal cardiac examination with color Doppler sonography and magnetic resonance imaging was very effective to interpret hypoplastic left heart syndrome with total anomalous pulmonary venous return. An accurate prenatal diagnosis of congenital heart anomalies is useful for obstetrical management. PMID- 7890260 TI - Effect of phenazone (antipyrine) on the prostanoid formation in human umbilical arteries perfused in vitro. AB - The influence of phenazone on the production of prostacyclin and thromboxane in human umbilical arteries was investigated by in vitro perfusion. With perfusate concentrations ranging from 10(-7) to 10(-4) M a decrease in the formation of both prostanoids was observed. The inhibitory effect of phenazone on prostanoid formation was found to be equal to that of indomethacin. PMID- 7890261 TI - Is granulocyte-macrophage colony-stimulating factor (GM-CSF) safe in myelodysplastic syndromes? AB - The complication of secondary myelodysplastic syndrome (sMDS) during the course of multiple myeloma (MM) has been recognized for more than a decade. sMDS occurs years after MM diagnosis, and typically, at sMDS presentation the MM is stable or inactive. We report a 56-year-old patient, who developed sMDS 15 years following the diagnosis of IgG-lambda MM, which had been completely stable for 13 years. However, very soon after sMDS was diagnosed, the MM relapsed and required combination chemotherapy. The first cycle of vincristine, adriamycin and dexamethasone (VAD) resulted in severe neutropenia and sepsis, which was treated with antibiotics and recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). Two weeks after GM-CSF administration a transformation to acute myeloblastic leukemia was observed. The relation between GM-CSF and the leukemic transformation is discussed and the possible contribution of the cytokine to the stimulation of this complication is emphasized. PMID- 7890262 TI - Haemorrheological changes in asthmatic Nigerian children. AB - A total of 73 children, 25 asthmatic patients in stable state, 23 in crisis state and 25 controls, nonasthmatic healthy individuals, age matched were studied. Relative plasma viscosity (RPV) and whole blood viscosity (RWBV) and fibrinogen levels were estimated. There were no significant differences between the controls and the stable asthmatic patients in any of the parameters measured. The fibrinogen concentration (p < 0.025), RPV and RWBV (p < 0.02) in asthmatic patients during an attack were significantly different from the respective values in the controls and the stable asthmatic patients. We conclude that hyperviscosity and hyperfibrinogenaemia may contribute to bronchitis and tissue damage during an asthmatic attack. PMID- 7890263 TI - Symptomatic versus asymptomatic patients in congenital hypoplasminogenemia: a statistical analysis. AB - In the present study, the prevalence of thromboembolic events in patients suffering from type I plasminogen deficiency was evaluated. One hundred and twelve affected subjects belonging to twenty-eight kindreds were gathered from the literature and from personal observations. The incidence of thrombosis found in this group was compared with those seen in: a) 86 unaffected family members; b) 100 hospitalized patients; c) 100 outpatient clinic patients. In the latter two groups, congenital clotting disorders were excluded. Thrombotic manifestations were found in 25.8% of patients with plasminogen deficiency, a figure which was statistically different from those found in unaffected family members (1.16%, p < 0.001), hospitalized patients (3%, p < 0.001) and outpatient clinic patients (5%, p < 0.001). In twenty-four kindreds with hypoplasminogenemia, data concerning the actuarial ages at first thrombotic event were available for construction of thrombosis-free survival curves by the Cutler Ederer method. The difference between the two curves, corresponding to affected and unaffected family members respectively, were statistically significant (p < 0.01). In conclusion, although the incidence of thromboembolic events in type I plasminogen deficiency is certainly lower than that described in other congenital clotting disorders such as AT III, protein C and protein S, patients with hypoplasminogenemia should be considered at risk for thrombosis, particularly when triggering factors are present. PMID- 7890264 TI - Secondary myelodysplastic syndrome in multiple myeloma--a study of nine patients with an attempt to detect myeloma patients at risk. AB - Over a follow-up period of ten years, nine of our 100 patients with multiple myeloma (MM), developed myelodysplastic syndrome (MDS, preleukaemia). MDS occurred 19-156 (median 35) months from the diagnosis of MM. Six patients presented with pancytopenia and no patients had active MM at the time of MDS diagnosis. Three patients were defined as having refractory anaemia (RA) and six as refractory anaemia with excess blasts (RAEB) or RAEB in transformation (RAEBT), according to the FAB classification. The clinical course is characterized by increasing red blood cell and platelet transfusion requirements, recurrent infections and bleeding episodes. All patients, except for one, died within 3 to 8 (median 5) months from MDS diagnosis. The causes of death were sepsis or bleeding; three patients underwent leukaemic transformation. Thus, the clinical course of this small group of myeloma patients who developed secondary MDS (sMDS), was similar to other series of patients with sMDS. Serial bone marrow examinations suggest an initial hypercellular phase, followed by a rapidly evolving preterminal hypocellular marrow. In an attempt to detect MM patients at risk of developing sMDS, the epidemiological (including ethnic), clinical and laboratory data of the 9 MDS patients at the time of the MM presentation were reviewed and compared to the other MM patients. No significant differences were observed between the two groups in most parameters, except for two. All MDS patients were Ashkenazi Jews and no patients of Sepharadic origin developed MDS. Also, no IgA-myeloma patient developed MDS. If these findings are confirmed in a larger series, it may point to subgroups at risk which may require a different approach.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7890265 TI - Prognostic significance of bone marrow reticulin fibres in idiopathic myelofibrosis: evaluation of clinicopathological parameters in a scoring system. AB - A clinicopathological scoring system was performed for obtaining a better estimate of prognosis in 50 patients with idiopathic myelofibrosis (IMF). Laboratory parameters including Hb-level, leukocyte and platelet counts, percentage of blast cells in peripheral blood, spleen and liver size, and a semiquantitative histological grading of reticulin fibre content of bone marrow biopsies taken at the time of initial diagnosis were analysed. Based upon these haematological and histological parameters three prognostic groups could be categorized with a significantly different survival (low-risk group with 21 patients = 75 months; medium-risk group with 18 patients = 51 months, and 11 patients in a high-risk group = 18 months). In an univariate (log rank test) and in a multivariate regression analysis the Hb-concentration, mild splenomegaly (less than 5 cm) and a higher grade of bone marrow reticulin content proved to be important prognostic parameters, whilst leukopenia, thrombocytopenia and the presence of peripheral blast cells were only of prognostic significance within the first 6 months from initial diagnosis. It was concluded that the increase of reticulin fibre deposition in bone marrow together with anaemia and mild splenomegaly could be responsible for a progressively worse life-expectancy of high-risk patients with idiopathic myelofibrosis. PMID- 7890266 TI - Efficacy of alpha interferon and hydroxyurea in late phase refractory myeloproliferative disease. AB - Three patients are described with late-stage myeloproliferative diseases, two with accelerated phase chronic myelogenous leukemia (CML) and one with refractory polycythemia vera (P vera), who achieved hematologic control after the addition of interferon (IFN) to hydroxyurea therapy. Both the CML patients continue to have a sustained clinical remission at 12 and 38 months. The patient with P vera had failed several previous treatments including busulfan, P32, hydroxyurea, and anagrelide, but became responsive after interferon use followed by reintroduction of hydroxyurea. Our observations support the efficacy of IFN alpha and hydroxyurea combination in late-phase myeloproliferative disease and warrants further clinical investigation. PMID- 7890267 TI - The therapeutic efficacy of VBCMP-M2 protocol in multiple myeloma. AB - Within a period from March 1983 to November 1988, 93 newly diagnosed patients with multiple myeloma, 47 men and 46 women aged from 41 to 80 years were treated with protocol VBCMP-M2. A response was achieved in 30 (60%) patients in stage II and 22 (51%) in stage III, the overall response rate being 56%. 41% of all patients entered plateau phase, more frequently in stage II (46%) than in stage III (37%) patients. The median survival of all patients was 35 months. Comparing these groups of patients with other series from the literature, we were not able to demonstrate any advantage of this multidrug combination over other combinations or even melphalan and prednisone alone. PMID- 7890268 TI - A new variant of von Willebrand's disease (type I Padua): doublet-organized plasma von Willebrand factor oligomers in the presence of all size multimers. AB - Type I von Willebrand's disease (vWd) is characterized by a concomitant decrease in plasma of von Willebrand factor antigen (vWf:Ag) and vWf ristocetin cofactor activity (vWf:RCoF), associated with the presence of all-size multimers. As a rule, there is no evidence of intrinsic abnormality in vWf. We describe a family with type I vWd with an abnormal plasma vWf multimer pattern. Analysis of plasma vWf multimeric structure by short-SDS-agarose gel electrophoresis showed an abnormal banding pattern for each vWf oligomer, which was organized as a doublet instead of the normal triplet. The electrophoretic mobility of each component appeared to be normal. Multimeric analysis on a long gel showed all the bands that were detectable in normal subjects, but unlike normals the fast moving satellite stained as the major component. The platelet vWf multimer pattern was normal. The infusion of DDAVP normalized vWf:Ag, vWf:RCoF and VIII:C, but not the abnormal multimer pattern observed on both short- and long-gel electrophoresis. The return of factor VIII/vWf complex to the baseline condition was more rapid than that observed in normal subjects or classic type I vWd patients. Analysis of the subunit fragments in the patients' plasma vWf demonstrated a relatively greater proportion, compared to the normal counterpart, of a 115(140)-kD fragment, which derives from the aminoterminal region of the mature molecule; in contrast, no intact subunit was detectable. These findings indicate a new, previously unreported, variant of type I vWd, which is characterized by plasma vWf oligomers organized as doublets, instead of triplets. The reduced post-DDAVP half-life, and the abnormal subunit fragments of vWf, suggest a molecule characterized by an increased susceptibility to proteolytic degradation. As a result, the decrease in circulating vWf levels may be due to an instability of the abnormal vWf, rather than, or in addition to, a decrease in its synthesis. PMID- 7890269 TI - [How HIV and HBV ensure their survival in the cell. Cytotoxic T-cells are impaired in their function]. PMID- 7890270 TI - [Diagnosis and therapy of hyperthyroidism. What is necessary--what is superfluous?]. PMID- 7890271 TI - [Differential diagnosis of hepatitis A, B, C, D and E. Clinical, biochemical and virus serologic criteria. 4: Hepatitis D serology]. PMID- 7890272 TI - [Comeback of the leech. Recombinant hirudin in anti-thrombosis therapy]. PMID- 7890273 TI - Molecular cytogenetics complements histopathology. PMID- 7890274 TI - Common clonal origin of synchronous primary head and neck squamous cell carcinomas: analysis by tumor karyotypes and fluorescence in situ hybridization. AB - Two synchronously arising primary squamous cell carcinomas (SCC) originating from separate sites in the anterior floor of mouth (FOM) and the pyriform sinus (PS) were evaluated by karyotype and fluorescence in situ hybridization (FISH) to determine whether they were of common or independent ancestry. The primary tumors were designated Henry Ford Hospital (HFH)-SCC-8a (FOM) and HFH-SCC-9a (PS), and the respective recurrent tumors after chemotherapy and radiation were designated 8b and -9b. HFH-SCC-8a and -8b were cultured and had closely related hypotetraploid karyotypes of monoclonal origin. Karyotypes could not be obtained from the second primary tumor HFH-SCC-9a or its recurrence -9b. However, we used karyotypes from HFH-SCC-8a and -8b as a guide to select FISH probes for the histological evaluation of genetic markers in tumor sections. Fluorescence in situ hybridization on metaphase chromosomes from the cell cultures was useful in modifying the tumor karyotypes. Fluorescence in situ hybridization identified a chromosome Y rearrangement that was not obvious from the HFH-SCC-8a and -8b karyotypes, and this Y rearrangement served as a unique clonal marker. Using two probes for the Y chromosome we showed that all four tumors shared the same Y rearrangement with loss of Yq (DYZ1) and retention of Ycen (DYZ3). Furthermore, FISH showed that all four tumors had the same aneuploidy patterns for chromosomes X, Y, 7, 9, 15, 16, and 17. From karyotypic and FISH analysis disomy for X and 9 centromere regions and the rearranged Y were all predicted and observed in the tumor tissue sections. Tetrasomy and trisomy for 7, 15, 16, and 17 were predicted from the karyotypes and this also was observed using FISH in all four tumors. These FISH aneuploidy patterns and the presence of a clonal Y marker in all four tumor samples indicate that the synchronous primaries and their recurrences were of monoclonal origin. PMID- 7890275 TI - The pattern of desmin filaments in myocardial disarray. AB - "Myofiber disarray" defines a nonparallel arrangement of cardiac myocytes. The presence of a sufficient quantity of myocardial fibers showing this change is considered to be a specific histological feature of hypertrophic cardiomyopathy (HCM). However, small zones of myofiber disarray are found in both cardiac hypertrophy and other pathological conditions. Recently, we demonstrated an altered pattern of desmin intermediate filaments in disarrayed myofibers from specimens of HCM. To test the hypothesis that desmin alterations might be specific for cardiomyopathy, we performed an immunohistochemical study on myocardial surgical samples from 11 patients with HCM and from 12 patients with tetralogy of Fallot (toF) on 14 endomyocardial biopsy specimens (EMBs) from transplant recipients with myofiber disarray surrounding areas of scarring (previous biopsy site) and on specimens of four autoptic hearts with severe acquired left ventricular hypertrophy. Disarrayed myofibers from all specimens of HCM showed the following abnormalities in the pattern of desmin intermediate filament distribution: (1) decrease or loss of labeling of intercalated discs and Z bands, (2) longitudinal arrangement of desmin intermediate filaments, and (3) intense, granular staining of several myocytes. This spectrum of desmin alterations was never observed in disarrayed myofibers in specimens of toF or acquired myocardial hypertrophy or in EMBs. Altered distribution of desmin intermediate filaments seems to be specific to myofiber disarray in HCM and it may play a role in the altered myocyte arrangement in HCM. PMID- 7890276 TI - Epstein-Barr virus-associated gastric adenocarcinoma in Taiwan. AB - Fifty-five gastric carcinoma tumors from Chinese patients in Taiwan, including 40 tubular type (one lymphoepthelioma-like carcinoma subtype), eight signet ring cell type, one papillary type, and six mucinous type gastric carcinomas, were investigated for the presence of Epstein-Barr virus (EBV) transcripts by in situ hybridization using fluorescein-conjugated EBV oligonucleotides for EBERs (Epstein-Barr virus early RNAs) expression and the polymerase chain reaction for viral DNA. Epstein-Barr virus was detected in six of 55 lesions (11%), a significantly lower proportion than has been observed in a North American series. Epstein-Barr virus involvement was more common among male patients. Epstein-Barr virus DNA and its EBERs were specifically present within gastric carcinoma and adjacent dysplastic cells but were absent in surrounding lymphocytes and normal gastric mucosa. Epstein-Barr virus DNA and EBERs were found in one sample of lymphoepithelioma-like carcinoma (LELC) and five specimens of typical gastric adenocarcinoma. Among the EBV-positive gastric adenocarcinomas, four were tubular type of varied differentiation and one was signet ring cell type. Furthermore, we evaluated the expression of the latent membrane protein (LMP) with monoclonal antibodies. We found that LMP was expressed in two EBV-positive samples. In addition, the presence of the EBV receptor was studied by probing samples with CD21 monoclonal antibody. Epstein-Barr virus receptor was not detected in any sample. Southern blot analysis indicated single clonal proliferation of tumor cells. These findings confirm and extend the results of Shibata et al. They also indicate that EBV infection might be related to oncogenesis not only in rare gastric cancers that resemble nasopharyngeal lymphoepithelioma but also in typical gastric adenocarcinoma. PMID- 7890277 TI - Expression of plurihormonal mRNAs in somatotrophic adenomas detected using a nonisotopic in situ hybridization method: comparison with lactotrophic adenomas. AB - We used a nonisotopic in situ hybridization (ISH) method to investigate the expression of pituitary hormone, including glycoprotein hormone mRNAs in 17 somatotrophic and four lactotrophic adenomas. Our ISH studies of lactotrophic adenomas showed that their hormonal gene expression was confined to prolactin, whereas those of somatotrophic adenomas showed that some of them expressed plurihormonal genes. In some somatotrophic adenomas that were immunohistochemically negative for pituitary hormones, positive reactions, mainly for adrenocorticotropic hormone (ACTH), follicle-stimulating hormone beta subunit (FSH beta), and luteinizing hormone beta subunit (LH beta) mRNAs, were observed in our ISH studies. These results suggest that some somatotrophic adenomas may originate from plurihormonal primordial stem cells, which we have presumed serve as precursors for various hormone-expressing cells. It is unclear why some somatotrophic adenomas derived from plurihormonal primordial stem cells manifest clinically only as the acromegalic hyperfunction syndrome or gigantism. Additional translational factors or some other somatic mutations may play important roles in the clinical manifestations of such adenomas. In conclusion, some somatotrophic adenomas appear to be derived from plurihormonal primordial stem cells, whereas lactotrophic adenomas are well differentiated tumors that originate from lactotrophic cells, which represent the final stage of acidophilic cell line differentiation. PMID- 7890278 TI - Diagnosis of malignant tumor: comparison between clinical and autopsy diagnoses. AB - A review was made of the results of 1,036 consecutive autopsies (average patient age, 75 years; 617 male and 419 female patients; autopsy rate, 40.2%) done at the Hospital of Monfalcone from January 1986 through December 1991. In 457 autopsies (44%) one or more malignant neoplasms were found (single tumor in 382, dual tumor in 69, and triple tumor in six) for a total of 538 tumors. In the corresponding death certificates the clinical diagnosis of malignancy was found in 302 autopsies for a total of 310 tumors (single in 294 and dual in eight). The number of clinically unrecognized malignancies was 228 (42%) and the number of patients with undiagnosed tumors was 155 (34%). The neoplasms were subdivided into four stages according to their extension at autopsy: stage 0 (85 tumors), microscopic neoplasm; stage I (146 tumors), neoplasm localized at the site of origin; stage II (43 tumors), local advanced neoplasm; and stage III (264 tumors), neoplasm with metastases. The rate of correct clinical diagnoses increased according to the level of stage; (stage 0, 1%; stage I, 40%; stage II, 58%; and stage III, 66%). The greatest numbers of tumors found at autopsy were located in the gastroenteric apparatus (170), the respiratory apparatus (149), and the urogenital apparatus (130). The number of clinically undiagnosed neoplasms was high with respect to the urogenital apparatus (77% overall and 51% excluding stage 0) and the gastroenteric apparatus (41% and 38% excluding stage 0); in contrast, the number was low for the respiratory apparatus (17%). The rate of correct diagnoses was higher in patients younger than 65 years (65%) than in those older than 65 (54%), but the difference was not significant. The duration of hospitalization in the 12 months before death was statistically higher (P < .001) in patients with a correct diagnosis (36 days) than in undiagnosed patients (14 days). Even taking into account the biases that affect selection of patients for autopsy, the notable discrepancy found between clinical and autopsy diagnoses underlines the fact that autopsy, despite improvements in diagnostic techniques, maintains its fundamental importance in assessing the reliability of clinical diagnoses and furthermore shows the underestimation of the incidence of tumors in epidemiological studies based solely on death certificates. PMID- 7890279 TI - Intratumoral activation of CD8-positive cytotoxic lymphocytes in acquired immunodeficiency syndrome lymphomas. AB - The incidence of lymphomas is unusually high in human immunodeficiency virus (HIV)-infected patients. Because cytotoxic T lymphocytes (CTL) represent a major mechanism of the antitumoral immune response in immunocompetent individuals, we asked whether intratumoral activation of CTL was impaired in acquired immune deficiency syndrome (AIDS) lymphomas. Immunohistochemical experiments showed that in AIDS lymphomas intratumoral CD8-positive T lymphocytes accumulated and expressed the TIA-1 antigen, a marker of cytotoxic cells. Flow cytometry studies and in situ hybridization of lymphomatous tissue confirmed the differentiation of CD8-positive cells in cytotoxic cells and their activation, as assessed by their expression of CD38 and human leukocyte antigen (HLA) DR markers as well as the perforin and granzyme B genes, which code for two molecules involved in target cell killing. On average, perforin-producing cells were as numerous in AIDS lymphomas (5,647 +/- 2,655 cells/cm2) as in lymphomas from immunocompetent individuals (3,294 +/- 1,544 cells/cm2). The density of activated CD8-positive cells in the 22 AIDS lymphomas tested was not correlated with peripheral CD4 positive cell counts. These results suggest that in AIDS lymphomas the steps of differentiation and activation of cytotoxic CD8-positive cells are not altered by immune deficiency and that they can take place through pathways relatively independent of CD4-positive T lymphocytes. Thus, other mechanisms of immune deficiency should account for the increased frequency of lymphomas in patients with AIDS. PMID- 7890280 TI - A new immunohistochemical antibody for the assessment of estrogen receptor status on routine formalin-fixed tissue samples. AB - We describe a method for the immunocytochemical assessment of estrogen receptor (ER) status on routinely processed, formalin-fixed tissue using a recently developed commercially available monoclonal antibody (Dako 1D5) with a microwave antigen retrieval technique. A series of 90 cases of human breast carcinoma was analyzed and the staining was assessed using a semiquantitative microscopic scoring method and by assessment of the percentage of nuclei showing positive staining. The results were compared with assessment using another commercially available antibody (Abbott H222) and with clinical response to tamoxifen therapy. Direct comparison of the paired sets of H scores and the percentage of positively stained nuclei using the two different techniques showed a significant correlation. By assigning an arbitrary cut-off for positivity of H score = 50, assessment of ER status using DAKO 1D5 antibody was found to correlate with response to tamoxifen therapy with a sensitivity of 90% and a specificity of 51%, similar to values in previous studies using other methods. We conclude that assessment of ER status using this new antibody and technique gives accurate results on routinely processed, formalin-fixed tissue and may be used as an alternative to other methods. PMID- 7890281 TI - An immunohistochemical study of p53 with correlations to histopathological parameters, c-erbB-2, proliferating cell nuclear antigen, and prognosis. AB - In an immunohistochemical study of 490 primary breast cancer patients with a follow-up period of more than 10 years, we found that p53 was not a prognostic factor for disease-free or overall survival among the whole cohort or among lymph node-positive or -negative patients. In a multiple logistic regression model classical histopathological parameters, such as lymph node status, number of mitoses, histological grade, and absence of progesterone receptors, were independent, poor prognostic predictors. In univeriate analysis p53 immunoreactivity was positively correlated with the absence of tubule formation, high histological grade (poor differentiation), absence of estrogen receptors (ER), and a high proliferating cell nuclear antigen (PCNA) score (ie, parameters indicative of an aggressive phenotype). The lack of prognostic significance may be attributable partly to the method used, because immunohistochemistry underdetects rather than overdetects p53 protein. No correlation between p53 and c-erbB-2-oncoprotein was demonstrated. PMID- 7890282 TI - Middle lobe syndrome: a clinicopathological study of 21 patients. AB - Middle lobe syndrome (MLS) is an uncommon lung disorder involving the right middle lobe and/or lingula and is characterized by a spectrum of clinical and pathological lesions ranging from recurrent atelectasis or pneumonias to bronchiectasis. Despite several series reporting the clinical features of MLS, histopathological descriptions are rare. We reviewed the clinical characteristics and pathological findings in 21 patients with MLS who underwent surgical resections. Six male and 15 female patients between the ages of 5 and 80 years (mean, 47 years) were studied. All patients were symptomatic and complained of chronic cough (8), hemoptysis (6), chest pain (4), dyspnea (3), or fever (2). The right middle lobe was involved in 11 patients, the lingula in four patients, and both right middle lobe and lingula in six patients. Chest radiographs, bronchograms, and/or computed tomography scans were available for review in 19 patients and showed consolidation (8), bronchiectasis (9), patchy infiltrates (5), and atelectasis (4) in various combinations. Pathological findings included bronchiectasis in 10 patients, chronic bronchitis/bronchiolitis with lymphoid hyperplasia in seven, patchy organizing pneumonia in six, atelectasis in five, granulomatous inflammation in five, and abscess formation in four. Three patients with granulomatous inflammation had associated atypical mycobacterial infection. Broncholithiasis was confirmed by pathological examination in one patient. No pathological cause for bronchial obstruction was identified in the remaining 20 patients, although one was thought to have had broncholithiasis on the basis of preoperative bronchoscopy. The presence of bronchiectasis, bronchitis or bronchiolitis, organizing pneumonia, or atelectasis in specimens from the right middle lobe or of lingula in the absence of an identifiable cause of bronchial obstruction should suggest a diagnosis of MLS. PMID- 7890283 TI - Immunohistochemical detection of advanced glycosylation end products within the vascular lesions and glomeruli in diabetic nephropathy. AB - Numerous studies over the years have implicated advanced glycosylation end products (AGEs) in the pathogenesis of many of the complications of diabetes and normal aging. The recent development of specific antibodies against AGE-modified proteins has facilitated investigations on the formation and tissue distribution of AGEs. We used anti-AGE antibodies to localize AGEs within kidney specimens obtained from both diabetic and nondiabetic individuals. Immunohistochemical staining using anti-AGE antibody showed a high level of AGE accumulation in diabetic and aged vascular intima, particularly along the inner elastic layer of arteries. Positive staining also was observed within nodular and severe diffuse lesions of glomeruli as well as in hyaline deposits of arterioles. These data support a pathogenic role for advanced glycosylation in the renal complications of diabetes and aging. PMID- 7890284 TI - Detection of Epstein-Barr virus in Hodgkin's disease occurring in an Oriental population. AB - Like Burkitt's lymphoma, the strength of association of Epstein-Barr virus (EBV) with Hodgkin's disease occurring in different populations and clinical settings is highly variable, being 30% to 50% in Western countries, nearly 100% in Third World countries like Peru and Honduras, and nearly 100% in patients seropositive for human immunodeficiency virus. Data on the Oriental populations are very limited. Therefore, the current study was performed on the Chinese population of Hong Kong, where the incidence of Hodgkin's disease is low and EBV seroconversion occurs early in life. Twenty-three consecutive samples of Hodgkin's disease collected from 18 male and five female patients over a 12-year period were studied. The first age peak occurred in the second decade of life, and the second peak in the seventh decade. Using the sensitive and specific EBV-encoded RNAs (EBERs) in situ localization technique, positive labeling of the Reed-Sternberg cells and their variants was detected in five of five samples (100%) of mixed cellularity, nine of 16 samples (56%) of nodular sclerosing, one of one sample (100%) of lymphocyte depleted, and none of one sample (0%) of nodular lymphocyte predominant Hodgkin's disease. Further analysis of the data by age group yielded the following results: four of five (80%) for age younger than 15 years, three of nine (33%) for age 15 to 49, and eight of nine (89%) for age 50 or higher, confirming the reported strong association of EBV with Hodgkin's disease at the extremes of life. The overall positivity rate was 65%, which was intermediate between that reported in the Western populations and that in the Third World countries. These findings can be explained by the epidemiological pattern of Hodgkin's disease in Hong Kong, in which the first age peak is left-shifted to a younger age compared with that of Western populations (but not as early as that observed in Third World countries), moving the peak toward an age bracket in which Hodgkin's disease shows stronger association with EBV. PMID- 7890285 TI - The human papillomavirus status of invasive cervical adenocarcinoma: a clinicopathological and outcome analysis. AB - Accumulating evidence highlights the human papillomavirus (HPV) as a risk factor for cervical adenocarcinoma. However, the part played by the HPV in predicting tumor outcome or the increasing frequency of cervical adenocarcinoma is incompletely studied. In a retrospective study the association between HPV status and the clinicopathological characteristics of 77 cases of cervical adenocarcinoma was investigated. The data were then analyzed for temporal differences in HPV status and to identify outcome predictors. Human papillomavirus status was determined by dot blot hybridization using probes for HPV 6, 11, 16, 18, 31, 33, and 35, followed by polymerase chain reaction amplification of the dot blot negative cases. Seven type-specific and consensus HPV primers were used. Human papillomavirus type 16, 18, or 33 was present in 53 (70%) cases. Human papillomavirus status did not correlate with disease outcome or any clinicopathological variable, except that tumors presenting in and after 1981 were more frequently HPV positive than those presenting before 1981 (P = .014). In a multivariate analysis only clinical stage at presentation was predictive of disease outcome. Because temporal differences in clinicopathological characteristics were not identified, the increasing frequency of cervical adenocarcinoma may relate to a more important oncogenic role for the HPV in tumors presenting after 1980. PMID- 7890286 TI - Immunohistochemical detection of aberrant p53 expression in hepatocellular carcinoma: correlation with cell proliferative activity indices, including mitotic index and MIB-1 immunostaining. AB - We analyzed the p53 expression immunohistochemically in 50 specimens of hepatocellular carcinoma (HCC) using two monoclonal antibodies (DO7 and PAb1801) and one polyclonal antibody (CM1), which recognize both wild and mutant type p53 proteins and can be used for paraffin-embedded sections. Fifteen of the 50 HCC specimens (30%) showed p53 expression localized at tumor nuclei, and this expression was significantly more frequent in HCCs with histologically lower differentiation. Except for serum titers of alpha-fetoprotein, the p53 expression had no statistically significant correlation with clinicopathological parameters, including hepatitis virus infection, tumor size, and background liver diseases. Conversely, the cell proliferative activities of tumor cells as assessed by mitotic index and immunostaining for MIB-1 were well correlated with the grade of histological differentiation. Moreover, MIB-1 immunostaining was shown to be useful in distinguishing well differentiated HCC from hepatocytes in chronic liver diseases. It also was shown that p53 expression was strongly associated with cell proliferative activity. Our results indicate that p53 expression takes place in the late stage of tumor progression and is related to the high malignant potential of HCCs. PMID- 7890287 TI - Immunohistochemical demonstration of the calcium-binding proteins MRP8 and MRP14 and their heterodimer (27E10 antigen) in Crohn's disease. AB - Monospecific antibodies against the calcium-binding proteins MRP8 and MRP14 and their heterodimer MRP8/14 (epitope 27E10) were used to investigate immunohistochemically the distribution of these proteins in routinely processed small and large bowel tissues from patients with Crohn's disease. MRP8, MRP14, and complex MRP8/14 were demonstrated in most granulocytes and macrophages in active Crohn's disease. Additionally, a strong complex MRP8/14 immunoreactivity was present in epithelial cells of the terminal ileum adjacent to ulcerative and fissuring lesions, whereas epithelial cells in large bowel tissues were consistently negative. Our results morphologically confirm the clinical finding of increased MRP8/14 serum levels in patients with active Crohn's disease; there is evidence that the serum MRP8/14 increase is caused by active secretion from granulocytes, monocytes, and epithelial cells. PMID- 7890288 TI - Ultrasound-guided fine-needle aspiration of parathyroid lesions: a morphological and immunocytochemical approach. AB - Ultrasound-guided (US) fine-needle aspiration (FNA) can successfully localize abnormal parathyroid tissue (PT) preoperatively in hyperparathyroid patients. Samples from 12 patients with primary hyperparathyroidism evaluated using this technique since 1990 at the National Institutes of Health form the basis of this report. Eleven patients had undergone previous parathyroid surgery that failed to correct their hyperparathyroidism. Cytological evaluation and C-terminal (midmolecule) parathyroid hormone radioimmunoassay (PTH RIA) were performed on all samples. When sufficient material was available, immunocytochemical stains for chromogranin and thyroglobulin were performed. All cytological diagnoses were made with-out knowledge of the PTH RIA results. Using a combined approach of cytology and immunocytochemistry, six of 12 of the samples (50%) were diagnosed as PT. Follow-up on these six patients was confirmatory. Four of 12 samples (33%) were identified as thyroid; one of these patients had a PT adenoma identified in another location (the remaining three patients await further localization studies). Two of 12 samples (17%) could not be diagnosed because of insufficient cellularity; in both patients PT lesions were found in other locations. Morphological features of PT in FNA include the presence of cellular tissue fragments with epithelial cells arranged perivascularly around capillary cores, an overall organoid or trabecular architecture, and frequent microacini. Parathyroid tissue cells have round, fairly uniform nuclei measuring 6 to 8 microns. Clusters of larger oxyphil cells may show considerable anisonucleosis. The absence of features of thyroid tissue such as hemosiderin-laden macrophages, abundant colloid, and paravacuolar granules is significant. However, in cases of intrathyroidal PT, admixed thyroid material included in the aspiration tract may be present immunocytochemical stains for chromogranin, which is present in parathyroid tissue but not thyroid follicular cells, were positive in six of six samples interpreted as PT by cytology. No thyroglobulin staining was observed in any of the four of six PT samples for which material was available. C-terminal (midmolecule) PTH RIA correlated with cytological diagnoses in 100% of samples. Parathyroid hormone levels ranged from 1,300 to 262,000 pg/mL (normal blood level, 50 to 340 pg/mL) in the six samples diagnosed as PT by cytology. Parathyroid hormone RIA levels in the six non-PT samples were below normal blood values. The combined approach of cytology and immunocytochemistry provides high diagnostic accuracy in the interpretation of US-guided FNA for preoperative localization of parathyroid tissue. PMID- 7890289 TI - Squamous intraepithelial neoplasia in an ovarian cyst, cervical intraepithelial neoplasia, and human papillomavirus. AB - A case of squamous intraepithelial neoplasia in an ovarian cyst in association with cervical intraepithelial neoplasia (CIN) III is described. In view of the association of human papillomavirus (HPV) and CIN, the possibility that HPV infection could be associated with similar changes in the ovary was postulated. The HPV genome was shown in formalin-fixed tissue of the cervical lesion by nonisotopic in situ hybridization (NISH) and by the polymerase chain reaction (PCR). However, HPV could not be shown in the ovarian lesion by NISH or PCR. On the basis of these findings there appears to be no association between HPV infection and squamous intraepithelial neoplasia in an ovarian cyst. PMID- 7890290 TI - Genotypic and immunohistological demonstration of the progression of an unusual reactive-like B-cell lymphoproliferative disorder to a high grade diffuse lymphoma. AB - In the present study the clinical and pathological evolution of a reactive-like B cell lymphoproliferative disorder with an unusually high content of T cells is described. Immunogenotypic analysis showed that the same phenotypically atypical B-cell clone, characterized by the unusual presence of an immunoglobulin (Ig)K gene rearrangement, with the heavy chain (IgH) gene in germline configuration, was invariantly present in all phases of the disease. The disorder showed an indolent course for a long period of time during which the clonal B-cell population coexisted with an abundant, reactive T-cell component in different locations of the disease. These findings, together with the observation of spontaneous progression and regression phases of the disorder and its responsiveness to corticosteroids, suggest that functional interactions between the B-cell clone and the polyclonal infiltrating T cells probably were involved in the pathogenesis of the disease. After the administration of the antiblastic treatment, a progressive reduction of the reactive T-cell component was observed with the concomitant evolution to a diffuse large cell (immunoblastic) B-cell lymphoma and the appearance of an IgH gene rearrangement. The biological characteristics and the clinical evolution of the case described here are similar to those reported for the so-called "T-cell-rich B-cell lymphomas" (TCRBCLs). These findings suggest that the T-cell-rich pattern may identify a group of B cell lymphoproliferations with common pathogenetic mechanisms and clinical behavior. PMID- 7890291 TI - Chaos and antichaos in pathology. PMID- 7890292 TI - Origins of C cells and follicular cells of the thyroid. PMID- 7890293 TI - Sex-determined susceptibility and differential IFN-gamma and TNF-alpha mRNA expression in DBA/2 mice infected with Leishmania mexicana. AB - Female DBA/2 mice have been shown to be relatively resistant to infection with Leishmania mexicana when compared with male mice. In order to determine the immunological basis behind this difference the draining lymph nodes from male and female DBA/2 mice were excised and the RNA extracted at different time-points following infection. Following reverse transcription, the polymerase chain reaction (PCR) was used to identify mRNA transcripts for interferon-gamma (IFN gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), IL-10 and IL-12. The evolution of cytokine mRNA production was slow in both male and female mice as no newly synthesized transcripts were identified 5 weeks after infection. IL-10 was expressed constitutively in non-infected mice and was present throughout the experiment in all animals. By week 8, a clear dichotomy in cytokine mRNA expression was emerging between the resistant female and susceptible male mice. Whereas all females expressed IFN-gamma and one also expressed TNF-alpha only two out of five males expressed IFN-gamma and four out of five expressed TNF-alpha. The greatest lesion sizes at this time were recorded from those mice expressing TNF-alpha but not IFN-gamma. No differences in IL-4 or IL-12 were noted with transcripts for both cytokines present in both sexes at week 8. By week 12 males had developed large non-healing nodules and in females lesions had either disappeared or were slow growing. At this time only transcripts for TNF-alpha were present in males and only those for IFN-gamma were detected in females. Treatment of female mice following infection with IFN-gamma neutralizing antibody resulted in lesion growth equivalent to male mice. IFN gamma production would, therefore, appear sufficient to limit the growth of L. mexicana in female DBA/2 mice while TNF-alpha production in the absence of IFN gamma confers no protection to DBA/2 male mice. PMID- 7890294 TI - Interaction between gamma delta T cells and B cells regulating IgG production. AB - Despite profound knowledge about the molecular structure of the gamma delta T cell receptor (TCR), the physiological function of gamma delta T cells remains enigmatic. Participation of these cells in complex immune reactions, however, is suggested by the appearance of gamma delta T cells in sites of infectious and autoimmune-induced inflammations. Only a few in vitro models of gamma delta T cell stimulation have been established: besides a reactivity in the presence of microbial ligands, human gamma delta T cells proliferate upon in vitro challenge with cells from an allogeneic B-lymphoblastic cell line (B-LCL). We present data here demonstrating that this reactivity is not confined to allogenic B-LCL. Autologous B-LCL are also very strong stimulators for gamma delta T cells; more important, autologous B cells can stimulate gamma delta T cells after a period of mitogen-activation but not in a resting state. This activation seems to address a subgroup of gamma delta T cells, as the percentage of V delta 1+ cells is increased after stimulation. Activated gamma delta T cells, on the other hand, are able to exert an influence on B cells by inhibiting the secretion of IgG in coculture experiments. These data define a simple regulatory circle of B cells and gamma delta T cells in vitro and propose a model for gamma delta T-cell function which could explain many in vivo observations of gamma delta T-cell activation. PMID- 7890295 TI - Host origin of follicular dendritic cells induced in the spleen of SCID mice after transfer of allogeneic lymphocytes. AB - Follicular dendritic cells (FDC) are uniquely characterized by the ability to trap immune complexes. In a previous report, it was shown that functional FDC with the capacity to trap immune complexes via complement receptor emerged in the splenic follicle after transferring syngeneic lymphocytes into the severe combined immunodeficiency (SCID) mouse. In the present report, we have investigated whether FDC are derived from haematopoietic cells or surrounding stromal components, by transferring allogeneic lymphocytes into SCID mice. Transfer of allogeneic T and B lymphocytes (H-2k) into SCID(H-2d) mice, however, failed to induce the development of FDC in the splenic white pulp. This was due to a graft-versus-host reaction (GVHR) by allogeneic lymphocytes against host stromal cells, as revealed by the destruction of the splenic reticular meshwork. The GVHR was prevented in transfer experiments of T-cell-depleted allogeneic lymphocytes with daily administration of anti-Thy-1 antibody. This resulted in segregated lodgement of allogeneic B lymphocytes in the proper compartments and, thereafter, generation of FDC in the primary follicle of SCID spleen, as revealed by the trapped immune complexes via complement receptors. The H-2 of the newly generated FDC was examined by two-colour immunofluorescent staining. FDC were defined as the reticular cells stained with anti-CR1/2 or FDC-M1 antibodies. FDC carried host H-2, clearly indicating that newly generated FDC are host-derived. In addition, the FDC shared the BP-3 protein with the surrounding reticular cells, a specific marker of reticular meshwork in the murine lymphoid tissues, and formed a network continuous with the rest of the reticulum, suggesting that FDC and non-FDC reticular cells belong to the same cell lineage. PMID- 7890296 TI - Generation of DC from mouse spleen cell cultures in response to GM-CSF: immunophenotypic and functional analyses. AB - In all tissues that have been studied to date, dendritic leucocytes constitute only a small proportion of total cells and are difficult both to isolate and purify. This study reports on a method for the propagation of large numbers of dendritic cells (DC) from mouse spleen using granulocyte-macrophage colony stimulating factor (GM-CSF) and their characteristics. Within a few days of liquid culture in GM-CSF, B10 BR (H-2k, I-E+) mouse splenocytes formed loosely adherent myeloid cell clusters. Mononuclear progeny released from these clusters at and beyond 4 days exhibited distinct dendritic morphology and strongly expressed leucocyte common antigen (CD45), CD11b, heat-stable antigen, Pgp-1 (CD44) and intercellular adhesion molecule-1 (ICAM-1; CD54). The intensity of expression of the DC-restricted markers NLDC 145 and 33D1, the macrophage marker F4/80, and Fc gamma RII (CDw32) was low to moderate, whereas the cells were negative for CD3, CD45RA and NK1.1. High and moderate levels, respectively, of cell surface staining for major histocompatibility complex (MHC) class II (I-Ek) and the B7 antigens (counter-receptors of CTLA4, a structural homologue of CD28) were associated with potent stimulation of unprimed, allogeneic T cells (B10; H 2b, I-E-). DC propagated in a similar fashion from DBA/2 mouse spleen proved to be strong antigen-presenting cells (APC) for MHC-restricted, syngeneic T-helper type 2 (Th2) cell clones specifically responsive to sperm whale myoglobin. Footpad or intravenous injection of GM-CSF-stimulated B10.BR spleen-derived DC into B10 (H-2b, I-E-) recipients resulted in homing of the allogeneic cells to T cell-dependent areas of lymph nodes and spleen, where they strongly expressed donor MHC class II antigen 1-2 days later. These findings indicate that cells can be propagated from fresh splenocyte suspensions that exhibit distinctive features of DC, namely morphology, motility, cell-surface phenotype, potent allogeneic and syngeneic APC function and in vivo homing ability. Propagation of DC in this manner from progenitors present in lymphoid tissue provides an alternative and relatively convenient source of high numbers of these otherwise difficult to isolate but functionally important APC. PMID- 7890297 TI - Serotonin regulation of T-cell subpopulations and of macrophage accessory function. AB - The role of serotonin as an immune modulator was investigated by measuring the functional competence of T cells from control mice versus from mice whose intracellular stores of serotonin had been depleted by pretreatment with p chlorophenylalanine (PCPA). While the proportions of splenic CD4+ and CD8+ T cells isolated from control and PCPA-treated mice were similar, the level of expression of the alpha-chain interleukin-2 receptor (IL-2R) was reduced on splenic CD4+ cells but not on CD8+ cells. Culture with the T-cell mitogen concanavalin A (Con A) failed to induce expression of the IL-2R on either CD4+ or CD8+ cells of PCPA-treated mice, although IL-2R was induced on control cells. The proliferative response to Con A by these spleen cells from PCPA-treated mice was also reduced compared to that by control spleen cells. Both expression of IL-2R and proliferation in response to Con A by spleen cells from serotonin-depleted mice were increased or completely restored by supplementation of the cultures with serotonin. Studies to identify the mechanisms for the reduction in T-cell activation when serotonin levels were reduced implicated a defect in the capacity of macrophages from PCPA-treated mice to provide accessory help for T-cell activation. Splenic macrophages from control mice were able to restore the blastogenic capability of lymphocytes from PCPA-treated mice, although macrophages from PCPA-treated mice were unable to support normal lymphocyte blastogenesis unless the cultures were supplemented with serotonin. These results show the requirement of autologous serotonin for optimal T-cell activation and suggest the importance of serotonin in macrophage accessory function for T-cell activation. PMID- 7890298 TI - Characterization of defectiveness in endogenous antigen presentation of novel murine cells established from methylcholanthrene-induced fibrosarcomas. AB - Three cell lines (4A1, 4C2 and 6D1 cells) derived from fibrosarcoma induced by the inoculation of 3-methylcholanthrene into C3H/HeN (H-2k) mice were examined for their ability to present antigens to CD8+ cytotoxic T lymphocytes (CTL). 6D1 and 4C2 cells were deficient in presenting endogenously synthesized influenza virus antigens to CTL, but they were able to present antigens when they were sensitized with a synthetic epitope peptide. The expression of the H-2 Kk gene in 4C2 and 6D1 cells was much reduced and was detectable only with Northern blot hybridization. The expression of two transporter genes (TAP1 and TAP2), examined by Northern hybridization, was also reduced in both cells, and negligible particularly in 4C2 cells. Interferon-gamma (IFN-gamma) treatment of these cells induced expression of Kk, TAP1 and TAP2 genes and rescued the defect of class I restricted antigen presentation in 4C2 and 6D1 cells. Even after this treatment, however, antigen-presentation capability of 4C2 cells was still much lower than that of normal 4A1 cells. This finding suggests that 4C2 cells might have an additional defective gene(s), whose products are involved in the processing of class I-restricted antigen, besides the Kk and TAP genes, and this may explain the difficulty of 4C2 cells to induce tumour-specific immunity, as described previously. To our knowledge, the 4C2 cell is the first tumour cell postulated to have more than three defective genes involved in class I-restricted antigen presentation. PMID- 7890299 TI - Unaltered immunoglobulin expression in hybridoma cells modified by targeting of the heavy chain locus with an integration vector. AB - Chimeric antibodies against the murine T-cell antigen Thy-1.2 were generated in amounts sufficient for in vivo studies by substituting the constant gene segments via homologous recombination in the hybridoma cell. We show that an integration vector targets the heavy chain locus at high frequency even in a non-isogenic situation. Using this vector type, for the first time expression rates were obtained that were identical to the parental hybridoma. The use of the gpt selection marker seems to be crucial for efficient expression, and may overcome a recently claimed drawback of vector integration. A chimeric antibody produced by gene targeting was characterized in vitro and in vivo. PMID- 7890300 TI - Studies on the role of interleukin-12 in acute murine toxoplasmosis. AB - Interleukin-12 (IL-12) is important in the regulation of resistance to Toxoplasma gondii in mice with severe combined immunodeficiency (SCID). The protective ability of IL-12 in SCID mice appears to be through its activity on natural killer (NK) cells to induce production of interferon-gamma (IFN-gamma). In this study we assessed the role of IL-12 in the acute stage of toxoplasmosis in immunocompetent mice. Administration of IL-12 to BALB/c mice infected with the virulent C56 strain of T. gondii remarkably delayed time to death. The protective activity of IL-12 was abrogated by administration of monoclonal antibodies to IFN gamma or tumour necrosis factor-alpha (TNF-alpha), and by depletion of NK cells using an antisera against asialoGM1. Whereas BALB/c mice infected with the ME49 strain of T. gondii survived infection, administration of anti-IL-12 to infected mice resulted in 100% mortality accompanied by decreased serum levels of IFN gamma. Furthermore, this treatment significantly reversed the suppression of spleen cell proliferation to concanavalin A (Con A), which is associated with the acute stage of infection, and resulted in decreased ex vivo production of IFN gamma, IL-2, IL-4 and IL-10 in response to Con A. Our results indicate an important role for IL-12 in mediating resistance to T. gondii during acute infection in immunocompetent mice, that NK cells are required for this protective activity, and that IL-12 is involved in the immunosuppression which accompanies this infection. PMID- 7890301 TI - Modulation of antigen processing and presentation by covalently linked complement C3b fragment. AB - Ligands such as complement fragments (C3, C4), IgG or alpha 2-macroglobulin, which bind antigen (Ag) before their uptake by antigen-presenting cells (APC), are likely to modulate the different steps of Ag processing and presentation. These ligands contribute to internalization and endosomal targeting of Ag; they also influence its processing and, consequently, the binding of resulting peptides to major histocompatibility complex (MHC) class II molecules before presentation to T cells. Complement protein C3 contains, like other members of the alpha 2-macroglobulin family, an intrachain thiolester bond. Conformational alteration or limited proteolysis of C3 into C3b leads to breaking of the thiolester with transient capacity of the revealed carbonyl group to esterify hydroxyl groups of Ag. Ester-linked complexes including tetanus toxin (TT) and C3b were prepared to analyse the influence of bound C3b on TT processing and presentation by APC. Covalent binding of C3b to TT resulted in increased and prolonged stimulation of specific T-cell proliferation. This effect was observed with non-specific B cells, as well as with a TT-specific B-cell clone, as APC. On the other hand, SDS-PAGE analysis of proteolysates of TT or C3b-TT, obtained with endosome/lysosome-enriched subcellular fractions prepared from human Epstein-Barr virus (EBV)-transformed B cells, indicated a delay of TT proteolysis when TT was associated to C3b. Treatment of APC with protease inhibitors, before and during exposure of the cells to Ag, resulted in differences in the inhibition of TT and C3b-TT proteolysis. Using purified cathepsins B and D, we demonstrated that covalent binding of C3b to TT totally abolished TT proteolysis by cathepsin D, while proteolysis by cathepsin B was preserved. This finding and the absence of cathepsin B in endosomes may explain a delay in TT processing when it is associated to C3b. Confirming these data, presentation by formaldehyde-fixed cells of C3b-TT proteolysates showed higher stimulation of specific T-cell clones than formaldehyde-fixed TT proteolysates. PMID- 7890302 TI - Soluble TNF receptor production by activated T lymphocytes: differential effects of acute and chronic exposure to TNF. AB - Soluble tumour necrosis factor receptors (sTNF-R) are up-regulated at sites of chronic inflammation such as rheumatoid synovial joints. The p75 sTNF-R is the more abundant, suggesting an important role for this TNF inhibitor in regulating TNF bioactivity in vivo. As the precise cellular source of these soluble receptors is not known, we investigated the production and regulation of sTNF-R by T lymphocytes, an abundant cell type in inflammatory infiltrates, which upon activation express high levels of p75 surface receptors. Using panels of T-cell lines and clones expressing high levels of p75 TNF-R, we found that p75 sTNF-R production upon stimulation is a feature common to all subsets of T cells, including cells of the CD4-CD8- double negative phenotype expressing either alpha beta or gamma delta T-cell receptors (TCR). In contrast, levels of p55 sTNF-R were only detected when T cells were stimulated at higher densities and by potent mitogens such as phorbol 12-myristate 13-acetate (PMA). Detailed kinetic analyses revealed that the production of p75 sTNF-R was biphasic, the first phase was activation dependent, occurring in the absence of detectable TNF, while the second phase of p75 sTNF-R production was regulated by cytokines such as TNF. Unlike short-term exposure to TNF which enhances sTNF-R production in vitro and in vivo, prolonged exposure of T lymphocytes to TNF suppressed p75 sTNF-R (but not p55 sTNF-R) production in a dose- and time-dependent fashion. These results suggest that in patients with chronic inflammatory disease, which are exposed to augmented levels of bioactive TNF for prolonged periods, the production of p75 sTNF-R may be impaired. PMID- 7890303 TI - Tumour necrosis factor-alpha is required for accumulation of dendritic cells in draining lymph nodes and for optimal contact sensitization. AB - Following skin sensitization epidermal Langerhans' cells (LC), many of which bear antigen, are stimulated to migrate from the skin and traffic via afferent lymphatics to lymph nodes draining the site of exposure. It has been proposed previously that tumour necrosis factor-alpha (TNF-alpha), a keratinocyte-derived epidermal cytokine (the expression of which is augmented following cutaneous sensitization), provides one signal for LC migration. In the experiments described here the influence of systemically administered neutralizing anti-TNF alpha antibody on dendritic cell (DC) accumulation in draining lymph nodes has been investigated. Treatment with anti-TNF-alpha inhibited markedly the frequency of DC in draining nodes measured 18 hr following exposure to the skin allergens oxazolone and fluorescein isothiocyanate or to the non-sensitizing skin irritant sodium lauryl sulphate. Similar treatment with anti-TNF-alpha 2 hr prior to primary exposure to oxazolone impaired significantly the efficiency of skin sensitization measured 5 days later as a function of challenge-induced increases in ear thickness. The same antibody administered 18 hr following initial exposure to oxazolone was without effect on skin sensitization. These data confirm the importance of TNF-alpha for the migration of LC from the skin to draining lymph nodes and demonstrate that this cytokine is required for optimal contact sensitization. PMID- 7890304 TI - LPS-induced 111In-eosinophil accumulation in guinea-pig skin: evidence for a role for TNF-alpha. AB - Lipopolysaccharide (LPS) is a major component of the cell wall of Gram-negative bacteria with powerful pro-inflammatory activities. Although the mechanisms involved in LPS-induced neutrophil accumulation have been studied extensively, few reports have focused on the effects of LPS on eosinophil infiltration. In this study we have used an in vivo model of local 111In-eosinophil accumulation in the guinea-pig to investigate the mechanisms of LPS-induced eosinophilia. Using a 4-hr in vivo test period, the intradermal injection of LPS (50-1000 ng/site) led to a marked and dose-dependent accumulation of 111In-eosinophils into guinea-pig skin sites. Time-course experiments revealed that this cell infiltration was delayed in onset, becoming significant 1 hr after the intradermal administration of LPS. The slow development of the response and its sensitivity to the locally administered protein synthesis inhibitor, actinomycin D, suggested that the LPS-induced 111In-eosinophil accumulation in vivo is mediated by the generation of de novo proteins. The intravenous pretreatment of guinea-pigs with a soluble tumour necrosis factor-alpha (TNF-alpha) receptor fusion protein (TNFR-IgG, 1 mg/kg), potently inhibited the 111In-eosinophil accumulation induced by LPS. Our results demonstrate that LPS can induce 111In eosinophil accumulation in vivo in guinea-pig skin, and that this process is mediated by TNF-alpha. PMID- 7890305 TI - Compound heterozygous complement C3 deficiency. AB - Complete deficiency of the third component of the complement system is a result of defects in the two alleles of the C3 gene. In this study a family with C3 deficiency is reported; the parents expressed a distinct abnormality of the C3 gene and their two children had compound heterozygous C3 deficiency. These are the first reported cases of compound heterozygous complement deficiency. Our results indicate that the maternal abnormality leads to synthesis of an abnormal proC3 protein which is not secreted from the cells. The paternal abnormality results in ablation of synthesis of the proC3 protein. PMID- 7890307 TI - Role of major histocompatibility complex class I antigens in modulating the performance of murine tumour cells in cold target competition assays. AB - The role of class I major histocompatibility complex (MHC) antigen levels on the ability of five murine tumour cell lines (YAC, P815, EL4, SP20 and L929) to competitively inhibit their own lysis, as well as the lysis of other targets by lymphokine-activated killer (LAK) effector cells was examined. Basal LAK susceptibilities of the cell lines were in the order P815 > YAC > SP20 > EL4 > L929, whereas the basal class I MHC antigen levels were in the order P815 > SP20 > L929 > YAC > EL4. Treatment with interferon-gamma (IFN-gamma) induced augmentation of class I MHC antigen levels on all cell lines. A concomitant decline in LAK susceptibility was seen for P815, YAC, SP20 and L929 cells, but not for EL4 target cells. On the basis of competition results, tumour cells appear to fall into two groups (group 1: P815, YAC and SP20; group 2: EL4 and L929). Members of each group could in general competitively inhibit the lysis of cell lines of their own group only. Treatment with IFN-gamma suppressed the ability of all tumour cell lines, except EL4, to cause competitive inhibition. These results support the proposition that class I MHC antigens may interfere with the recognition of target cells by effector LAK cells. PMID- 7890306 TI - Expression of TGF-beta in attenuated Salmonella typhimurium: oral administration leads to the reduction of inflammation, IL-2 and IFN-gamma, but enhancement of IL 10, in carrageenin-induced oedema in mice. AB - Mice injected with carrageenin in the footpad developed local inflammation which peaked at 48 hr. This was significantly reduced in mice inoculated orally with an attenuated Salmonella construct expressing transforming growth factor-beta (TGF beta). Administration of the Salmonella construct alone had no effect on inflammation. High levels of interleukin-2 (IL-2) and interferon-gamma (IFN gamma) were secreted by draining lymph node cells from mice injected with carrageenin following stimulation in vitro. Prior inoculation with Salmonella enhanced the production of IL-2 and IFN-gamma from the draining lymph node cells. Administration of the Salmonella-TGF-beta construct significantly inhibited the production of these cytokines. In contrast, IL-10 only was secreted from draining lymph node cells of animals inoculated with the Salmonella-TGF-beta construct. Thus, oral administration of TGF-beta can significantly inhibit local inflammation and alter the cytokine secretion pattern of cells from lymph nodes draining the site of inflammation. PMID- 7890308 TI - Human cord blood T-cell receptor alpha beta cell responses to protein antigens of Paracoccidioides brasiliensis yeast forms. AB - Paracoccidioides brasiliensis causes a chronic granulomatous mycosis, prevalent in South America, and cell-mediated immunity represents the principal mode of protection against this fungal infection. We investigated the response of naive cord blood T cells to P. brasiliensis lysates. Our results show: (1) P. brasiliensis stimulates T-cell expansion, interleukin-2 (IL-2) production and differentiation into cytotoxic T cells; (2) T-cell stimulation depends on P. brasiliensis processing and major histocompatibility complex (MHC) class II expression; (3) the responsive T-cell population expresses alpha beta T-cell receptors (TCR) with different V beta gene products, CD4 and CD45RO; (4) the P. brasiliensis components involved in T-cell expansion primarily reside in a high molecular weight (100,000 MW) and a low molecular weight (< 1000 MW) protein fraction. These results indicate that protein antigens of P. brasiliensis stimulate cord blood CD4 alpha beta T cells, independent from in vivo presensitization, and thus question direct correlation of positive in vitro responses with protective immunity in vivo. PMID- 7890309 TI - An endogenous lectin, galectin-3 (epsilon BP/Mac-2), potentiates IL-1 production by human monocytes. AB - Galectin-3 is a member of a growing family of beta-galactoside-binding animal lectins and previously designated as epsilon BP (IgE-binding protein) by this laboratory and as Mac-2, CBP35, L-34 and L-29 by other researchers. While possible intracellular functions have been proposed for galectin-3, existing data also suggest an extracellular modulatory role of this lectin. For example, epsilon BP/Mac-2 was found to be secreted by various cells and capable of activating mast cells, possibly through cross-linking of cell surface glycoproteins involved in cell activation. In this study, we showed that epsilon BP bound to human monocytes via its lectin function. Furthermore, we found that epsilon BP potentiated IL-1 production by monocytes in a manner that was inhibitable by the saccharide ligand of epsilon BP. The results further support a role of this lectin in potentiating activities of inflammatory cells and thereby amplifying inflammatory responses. PMID- 7890310 TI - L3T4+ but not LYT2+ T-helper cells are required for in vitro maturation of in vivo primed T cells in the cytotoxic response to MHC class I disparate cells following footpad immunization. AB - The induction characteristics of major histocompatibility complex (MHC) class I specific cytotoxic T lymphocytes (CTL) after footpad immunization were studied. Primary CTL were generated in the regional lymph nodes of C57Bl/6 mice by footpad injection with 10(7) irradiated (2000 rad) spleen cells from MHC class I mutant mouse strain (bm1) followed by a short in vitro culturing without antigen. The requirement of accessory cells and L3T4+ T cells during in vitro maturation of in vivo primed CTL precursor (CTLp) was shown. Moreover, using inhibitory antibodies, the need for IL-2 and IL-4 for in vitro maturation of CTL was established. We have suggested that accessory cells act at the level of L3T4+ T cells which in turn non-specifically up-regulate the CTL response through the production of growth and differentiation factors. Thus, the T-helper population of L3T4+ but not Lyt2+ phenotype appears to be recruited in the in vitro maturation of in vivo primed CTLp in a given system. Possible mechanisms of this phenomenon are discussed. PMID- 7890311 TI - Lymphocyte lines under iron-depriving conditions: transferrin receptor expression related to various growth responses. AB - The relation of expression of cell surface transferrin receptors to growth responses under defined iron-depriving conditions was studied in mouse B-cell line PLV-01, human T-cell line Jurkat, and human B-cell line Raji. Iron chelator deferoxamine at a concentration of 150 microM, which inhibited completely growth of the cell lines cultured in a serum-free transferrin-containing (5 micrograms/ml) medium, stimulated the surface transferrin receptor number to increase to 150-250% within a 24-h incubation period. The increased number (300%) of transferrin receptors on PLV-01 cells was associated with complete growth inhibition of these cells in counterpart serum-free transferrin-free medium. Only a slight increase in transferrin receptor number on Raji cells corresponded with unaffected growth of these cells in the transferrin-free medium. Jurkat cells increased the number of transferrin receptors to 150-200% and decreased the number of cells grown in the transferrin-free medium to about 60%. The data show that, under limited availability of iron, a significant increase of transferrin receptor expression on lymphoid cells was found only when the growth of the cells was inhibited. However, complete inhibition of growth achieved under different iron-depriving conditions is accompanied by different degrees of increase in transferrin receptor number. PMID- 7890312 TI - Effect of interleukin-10 on NF-kB and AP-1 activities in interleukin-2 dependent CD8 T lymphoblasts. AB - Interleukin-10 is a multifunctional cytokine, which regulates the function of various cell types of the immune system. In CD8 T cells it is known to accelerate the interleukin-2 dependent proliferation and to induce the differentiation of these cells to active cytolytic cells. Now we have studied interleukin-10 induced intracellular signaling mechanisms in human interleukin-2 dependent CD8 T lymphoblasts. The data obtained demonstrate that interleukin-10 alone can activate the AP-1 transcription factor and potentiate the interleukin-2 induced NF-kappa B activity. Moreover, interleukin-10 induced a rapid tyrosine phosphorylation of several proteins. The pattern of proteins phosphorylated was very similar to that induced by interleukin-2. Together, these findings suggest that tyrosine kinase dependent activation of NF-kappa B and AP-1 transcription factors are involved in the signaling mechanism of interleukin-10. This activation pathway resembles that of interleukin-2 in the same cell type. PMID- 7890313 TI - Constitutive and cytokine-induced production of interleukin-6 by human myoblasts. AB - Several recent studies have shown that some inflammatory myopathies are autoimmune diseases. It is possible that certain alterations in the muscle-immune cell microenvironment and in the local production of cytokines could take part in the pathogenesis of inflammatory myopathies. In the present study we investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN gamma) on the secretion of interleukin-6 (IL-6) by myoblasts. Purified human myoblasts from normal subjects and from patients with polymositis were cultured in the presence of TNF-alpha and IFN-gamma at two concentrations (100 and 200 U/ml), alone or in combination, for 12, 24 and 48 h. The supernatants were collected and the IL-6 concentrations tested by ELISA (Genzyme). We found that myoblasts secrete IL-6 constitutively. The secretion of IL-6 was greatly increased by TNF-alpha; the increase was both time- and dose-dependent. IFN-gamma caused a moderate increase in IL-6 secretion, but this effect was not significant, despite a slight positive trend over time. There was no synergism in the effect of IFN-gamma and TNF-alpha. It is known that inflammatory myopathies are characterized by mononuclear cell infiltration and muscle regeneration: myoblasts are present in infiltrated tissues. Thus, the local production of cytokines that characterizes the inflammatory reaction, could stimulate myoblasts to secrete IL-6, which might add to the pro-inflammatory effects of IL-6 produced by activated macrophages and T cells. PMID- 7890314 TI - BALB/c mice infected with Brucella abortus express protracted polyclonal responses of both IgG2a and IgG3 isotypes. AB - A polyclonal IgG2a response dependent on the secretion of endogenous IFN-gamma has been demonstrated in BALB/c mice injected with killed whole cells of Brucella abortus [1]. Here we report intense and protracted polyclonal responses of IgG2a and also of IgG3 isotypes in BALB/c mice undergoing primary infections with B. abortus attenuated vaccine strain 19 or virulent strain 2308. Ratios of total serum Ig levels between infected mice and age matched controls were greater than 38 for IgG3 and greater than 12 for IgG2a between weeks 4 and 8 post-infection. Polyclonal increases of IgM and IgG1 that were proportionally much lower (ratios < 2 and < or = 3, respectively) also occurred in infected mice during this time. It is hypothesized that both IgG3 and IgG2a polyclonal responses required IFN gamma, which was induced by B. abortus primarily in a T cell-independent fashion during the first weeks of infection, and from T cells thereafter. PMID- 7890315 TI - Enhancement of natural antibodies in mice immunized with exoantigens of pI 4.5 from Trypanosoma cruzi. AB - This paper deals with the enhancement of natural antibodies in mice immunized with a previously purified exoantigen of Trypanosoma cruzi from infected mouse plasma by isoelectric focusing, called Ea 4.5. A simultaneous rinse of IgG antibodies recognizing acidic sciatic nerve antigen (SNA) and other conserved antigens such as myoglobin, actin, thyroglobulin, and tubulin was observed. The highest level of antibodies was revealed when myoglobin was used as antigen in the ELISA test. Good correlation was found between the level of antibodies reactive with SNA and with highly conserved antigens. Furthermore, absorption experiments showed that a fraction of antibodies binding SNA are polyreactive and also react with the highly conserved antigens. The histological studies of sciatic nerve, heart and skeletal muscle performed 1 month after the last immunization revealed no modifications with respect to the control animals. Based on these and a previous result [1], indicating that injection of Ea 4.5 induced in mice a partial protection against T. cruzi, the possibility exists that a percentage of antibodies induced by Ea 4.5 may correspond to the natural autoantibody type and take part in protective and/or pathogenic effects. PMID- 7890316 TI - IFN gamma and TNF alpha cause an increased release of C3 by murine macrophages. AB - Macrophages from mice bearing Lewis lung carcinoma release higher amounts of C3 molecules than macrophages from healthy mice. The C3 pro-releasing activity operating in vivo was suspected to be due to an immunological network. Indeed, the supernatants of splenocytes from tumor bearing mice, but not from normal mice, induced in vitro an increased release of C3 molecules by macrophages. Recombinant IFN gamma and TNF alpha were strong inducers of C3 release, while IL 2 acted poorly. The C3 pro-releasing activity of splenocyte supernatants was largely prevented by their pretreatment with specific mAb anti IFN gamma or anti TNF alpha, but not completely prevented by the simultaneous neutralization of the two cytokines. Taken together, these results show that murine macrophages increase the release of C3 molecules upon treatment with IFN gamma or TNF alpha and that these cytokines released in vivo by splenocytes from tumor bearing mice may account, together with a yet unknown factor, for a humoral network causing the increased release of C3 by peritoneal macrophages. PMID- 7890317 TI - Lymphocytes from the site of disease are functionally different from peripheral blood lymphocytes and may demonstrate etiologically related antigen specificity. AB - Over a 12-year period, in vitro synovial lymphocyte responses to microbiological antigen stimulation were measured by the [3H]thymidine uptake method in referred patients with all types of non-crystal, non-septic, inflammatory arthritis. From this large study group comparisons of synovial with peripheral blood lymphocyte (PBL) responses were available in 9 patients with enteric reactive arthritis (ERA), 12 patients with sexually acquired reactive arthritis (SARA) and 18 patients with recurrent or persistent oligoarthritis or with polyarticular 'rheumatoid' arthritis. Employing 2-tailed t tests, analysis of variance (ANOVA) or meta-analysis, as appropriate to the obtained data, significant differences were found between synovial and peripheral blood responses. In only 2 of 9 patients with bacteriologically defined ERA, in only 4 of 12 patients with SARA and in only 2 of 18 patients with oligoarthritis or 'rheumatoid' arthritis did the PBLs show statistically significant responses to the antigen that elicited a significant response from synovial lymphocytes. It is concluded that lymphocytes from the site of disease are often functionally different from PBLs and may demonstrate etiologically related antigen specificity; thus they may be a preferred source of lymphocytes for the investigation of immunologically mediated disease, the etiology of which is not understood. This viewpoint is supported by a recent paper on the specificity of hepatic lymphocytes for a protein of hepatitis C in patients with chronic hepatitis C, and also by the use of tumour infiltrating lymphocytes for anti-melanoma therapy. PMID- 7890318 TI - Factor J, a human inhibitor of complement C1, is a cationic, highly glycosylated protein. AB - Factor J (FJ) is a new inhibitor of the complement system. This work supports the fact that FJ is a cationic molecule (pI > or = 9.6 in native conditions, or pI = 8.1 in denaturing conditions) with a high sugar content (40%) that is able to interact with different lectins, suggesting a complex glycosylation. SDS impaired FJ migration in polyacrylamide gel electrophoresis. In Triton-acid-urea polyacrylamide gel electrophoresis FJ migrated as a complex, dispersed molecule. In contrast, FJ after Smith degradation (dFJ) gave a single, smeared band of M(r) = 23.4 kDa in reducing SDS-PAGE. dFJ retained only 60% of the initial inhibitory activity of intact FJ. When digestions with different proteinases were performed, no modification of activity was observed. After beta-glucuronidase digestion, FJ lost 80% of its initial activity. Consequently, glycosylation plays an important role in the inhibitory activity of FJ. PMID- 7890319 TI - Cationization of a monoclonal antibody to the human immunodeficiency virus REV protein enhances cellular uptake but does not impair antigen binding of the antibody. AB - Replication of the human immunodeficiency virus (HIV) within cells may be blocked by neutralization of viral-specific proteins that are absolutely required for growth of the virus. One such viral-specific protein is REV, and a monoclonal antibody (mAb) against the REV protein is a potential therapeutic for acquired immune deficiency syndrome (AIDS). However, in order to effect 'intracellular immunization', mAbs must be enabled to target the intracellular compartment. One strategy for transcellular drug delivery of mAb-based therapeutics is cationization, and the present studies describe the cationization of a murine mAb specific to the REV protein of HIV-1. The isoelectric point (pI) of the mAb was raised from 6.6 to more than 9.5. There was virtually no difference in binding to wild-type REV protein between the native or cationized anti-REV mAb, based on studies with a solid-phase immunoradiometric assay. The uptake of the [125I] native anti-REV mAb by human peripheral blood lymphocytes (PBLs) was negligible; however, there was a marked increase in both total cell binding and endocytosis by the human PBLs of the [125I] cationized anti-REV mAb. In conclusion, these studies show that an anti-REV mAb may be cationized to markedly increase endocytosis of the antibody and that this cationization reaction does not significantly alter the affinity of the antibody for its target protein. Cationized anti-REV mAbs may allow for intracellular immunization of the virus and are potential therapeutics for the treatment of HIV. PMID- 7890320 TI - Effect of phytohaemagglutinin on CD45 in T cells. AB - In this study the effect of PHA activation on the phosphatase activity of CD45 has been investigated in human leukemic T-cell lines. It has been found that in vivo activation of the cells with PHA resulted in 2-4-fold increase in enzyme activity. Addition of PHA to the postnuclear supernatant of cell lysates also resulted in elevation of phosphatase activity. Elevation of enzyme activity resulted from an increase in the amount of antigen in the immunoprecipitates. Elevation of the quantity was not the result of a de novo protein synthesis since the presence of cycloheximide, a protein synthesis inhibitor, did not modulate the effect of PHA. The effect of PHA was specific since ConA, that also bound to the CD45 molecules, or crosslinking of the antigen by antibody did not affect CD45. Since direct binding of PHA to CD45 molecules was shown in immunoblotting analysis, we suggest that the effect of PHA is a consequence of a PHA-induced conformational change of CD45 that results in up-regulation of the analyzed CD45 epitopes. PMID- 7890321 TI - Induction of specific IgA responses in rats after oral vaccination with biodegradable microspheres containing a recombinant protein. AB - Diseases which affect mucosal surfaces cause considerable mortality and morbidity. New vaccine technologies are now available which justify a reappraisal of oral delivery not only for infectious disease control but also to control mucosal physiological processes such as fertility. Biodegradable microspheres have been investigated for their use as an oral delivery vehicle in rats using a recombinant antigen derived from fox sperm. Unencapsulated antigen administered in saline by the oral route produced a negligible response although an improved response was obtained if administered directly into the duodenum. This response was considerably enhanced if Peyer's patch (PP) priming was performed by direct injection of antigen in Freund's complete adjuvant (FCA) prior to intraduodenal (ID) delivery. In contrast, microencapsulated antigen given orally produced a substantial response, which was predominantly IgA specific, and almost equal in magnitude to that obtained by PP priming and ID boosting with native antigen. Direct ID delivery produced a similar response but when PP were primed with microencapsulated antigen in FCA the response to ID boosting was greater than with any of the other protocols investigated. These data demonstrate the efficacy of biodegradable microspheres in producing an IgA antibody response following oral vaccination. PMID- 7890322 TI - Positive selection of V beta 10 in NOD mice protected from diabetes by an Ea transgene. PMID- 7890323 TI - In memoriam. A brief journey into the life of Donald Shreffler. PMID- 7890325 TI - Major histocompatibility complex class II A gene polymorphism in the striped bass. AB - Adaptions of the polymerase chain reaction were used to isolate cDNA sequences encoding the Major histocompatibility complex (Mhc) class II A gene(s) of the striped bass (Morone saxatilis). Four complete Mhc class II A genes were cloned and sequenced from a specimen originating in the Roanoke River, North Carolina, and another three A genes from a specimen originating from the Santee-Cooper Reservoir, South Carolina, identifying a total of seven unique sequences. The sequence suggests the presence of at least two Mhc class II A loci. The extensive sequence variability observed between the seven different Mhc class II clones was concentrated in the alpha 1 encoding domain. The encoded alpha 2, transmembrane, and cytoplasmic regions of all seven striped bass genes correlated well with those of known vertebrate Mhc class II proteins. Overall, the striped bass sequences showed greatest similarity to the Mhc class II A genes of the zebrafish. Southern blot analysis demonstrated extensive polymorphism in the Mhc class II A genes in members of a Roanoke river-caught population of striped bass versus a lesser degree of polymorphism in an aquacultured Santee-Cooper population of striped bass. PMID- 7890327 TI - Transfection, expression, and DNA sequence of a gene encoding a BoLA-A11 antigen. PMID- 7890326 TI - Association of H2Ab with resistance to collagen-induced arthritis in H2 recombinant mouse strains: an allele associated with reduction of several apparently unrelated responses. AB - HLA class II alleles can protect against immunological diseases. Seeking an animal model for a naturally occurring protective allele, we screened a panel of H2-congenic and recombinant mouse strains for ability to protect against collagen induced arthritis. The strains were crossed with the susceptible strain DBA/1, and the F1 hybrids immunized with cattle and chicken type II collagen. Hybrids having the H2Ab allele displayed a reduced incidence and duration of the disease. They also had a reduced level of pre-disease inflammation, but not of anti collagen antibodies. The allele is already known to be associated with reduction of other apparently unrelated immune responses, suggesting that some form of functional differentiation may operate that is not exclusively related to epitope binding. It is suggested that this may reflect allelic variation in the class II major histocompatibility complex promoter region. PMID- 7890328 TI - Genetic polymorphism of the mouse major histocompatibility complex-associated proteasome subunit Lmp7. PMID- 7890329 TI - Blood monocytes and spleen macrophages differentiate into microglia-like cells on monolayers of astrocytes: morphology. AB - Several morphological and functional properties of microglial cells, the resident immunoeffector cells of the central nervous system (CNS), differ from those of monocytes/macrophages in other tissues. Microglia are assumed to derive from myelonocytic lineage, possibly as a distinct subpopulation that diverges from a common cell line early in ontogeny, invades the CNS, proliferates, and differentiates into ameboid and then ramified microglia. We tested the hypothesis that some morphological and functional properties of microglia are induced in myelomonocytic cells by nervous tissue, specifically astrocytes. In the present in vitro studies we compared the differentiation of microglia, blood monocytes, and spleen macrophages on acellular substrates and on monolayers of astrocytes and fibroblasts. On acellular substrates, microglial cells at first acquire an ameboid morphology; later they show a few short, unbranched processes. On monolayers of pure astrocytes, microglial cells at first also differentiate into ameboid cells, but after 5 to 7 days they start to develop processes with large lamellopodial tips. These lengthen and branch continuously during the next 2 weeks in vitro, demarcating a round to oval territory around the small ellipsoid cell body. By contrast, on monolayers of fibroblasts the microglial cells develop an ameboid morphology, but do not grow the typical long branched processes of the ramified form. Blood monocytes and spleen macrophages behave indistinguishably from microglia both on acellular and cellular substrates, i.e., on astroglia they develop the ramified form, while on fibroblasts they retain the ameboid shape. When microglia, macrophages, or monocytes are cultured on coverslips on top of astrocytic monolayers, i.e., physically separated from the astroglia, but exposed to the medium conditioned by astrocytes, a significant proportion of them also develop the ramified shape. These findings indicate that the ramified shape of microglia is induced by astrocytes. Since this morphology can also be induced in blood monocytes and macrophages, we take this to be further evidence for the proposition that microglial cells are derived from the myelomonocytic lineage, and, moreover, that properties of resident macrophages are largely determined by tissue components of their host organ. PMID- 7890331 TI - Ca2+ influx into leech glial cells and neurones caused by pharmacologically distinct glutamate receptors. AB - The effect of glutamatergic agonists on the intracellular free Ca2+ concentration ([Ca2+]i) of neuropile glial cells and Retzius neurones in intact segmental ganglia of the medicinal leech Hirudo medicinalis was investigated by using iontophoretically injected fura-2. In physiological Ringer solution the [Ca2+]i levels of both cell types were almost the same (glial cells: 58 +/- 30 nM, n = 51; Retzius neurones: 61 +/- 27 nM, n = 64). In both cell types glutamate, kainate, and quisqualate induced an increase in [Ca2+]i which was inhibited by 6,7-dinitroquinoxaline-2,3-dione (DNQX). This increase was caused by a Ca2+ influx from the extracellular space because the response was greatly diminished upon removal of extracellular Ca2+. The glutamate receptors of neuropile glial cells and Retzius neurones differed with respect to the relative effectiveness of the agonists used, as well as with regard to the inhibitory strength of DNQX. In Retzius neurones the agonist-induced [Ca2+]i increase was abolished after replacing extracellular Na+ by organic cations or by mM amounts of Ni2+, whereas in glial cells the [Ca2+]i increase was largely preserved under both conditions. It is concluded that in Retzius neurones the Ca2+ influx is predominantly mediated by voltage-dependent Ca2+ channels, whereas in neuropile glial cells the major influx occurs via the ion channels that are associated with the glutamate receptors. PMID- 7890330 TI - Blood monocytes and spleen macrophages differentiate into microglia-like cells on monolayers of astrocytes: membrane currents. AB - Microglia, the resident macrophages of the central nervous system (CNS), can be distinguished from most other cells of the myelomonocytic lineage by a distinct pattern of membrane currents. In the accompanying paper we have shown that the characteristic morphological feature of microglia, ramification, develops both in microglia and other myelomonocytic cells when they are cocultured with astrocytes. We therefore propose that the electrophysiological properties of microglia also develop under the influence of astrocytes, and, moreover, that these properties can also be induced in other cells of the myelomonocytic lineage. Microglia cultured on poly-d-lysine or on a monolayer of fibroblasts possess an inwardly rectifying K(+)-current only, which is of composite nature. In single-channel recordings two types of K(+)-channels are found: i) a noninactivating channel with a conductance of 43pS, and ii) an inactivating channel with 32pS. Microglia cultured on a monolayer of astrocytes additionally develop an outward K(+)-current and a Na(+)-current. The electric parameters of activation and inactivation of the microglial Na(+)-current are identical to those of the neuronal Na(+)-current. Monocytes from peripheral blood and macrophages from spleen exhibit no inward currents. However, when these cells are cocultured with astrocytes they develop microglia-like membrane currents, including the inward and outward K(+)-rectifyer and the Na(+)-current. By contrast, on fibroblasts they retain their macrophage current profile. The expression of the microglia-like membrane currents in the mononuclear phagocytes is induced by a diffusible factor released from the astrocytes into the culture medium, since monocytes and microglia develop the mature microglial current profile, when cultured in astrocyte conditioned medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7890324 TI - MHC ligands and peptide motifs: first listing. PMID- 7890332 TI - Normal and pathological expression of GFAP promoter elements in transgenic mice. AB - The expression of the glial fibrillary acidic protein (GFAP), a component of astroglial intermediate filaments, is regulated under developmental and pathological conditions. In order to characterize DNA sequences involved in such regulations, we produced transgenic mice bearing 2 kb of the 5' flanking region of the murine GFAP gene linked to the Escherichia coli beta-galactosidase (beta gal) reporter gene. Seven transgenic lines were obtained. We observed that the regulatory elements present in the transgene GFAP-nls-LacZ direct an expression in the neural and non-neural tissue and target in vivo an unexpected subpopulation of astrocyte. In the developing brain, beta-gal activity and GFAP appeared simultaneously and in the same region, on embryonic day 18 (E18), suggesting that the 2 kb of the promoter contains the regulatory sequences responsible for the perinatal vimentin/GFAP switch. In addition, we demonstrated that the 2 kb sequence of the GFAP promoter used in the transgene possess elements which are activated after a surgical injury, thus permitting to study some aspects of reactive gliosis in these transgenic mice. These transgenic lines provide a useful tool by enabling further studies of astroglial and, probably, neuronal physiologies. PMID- 7890333 TI - GM-CSF promotes proliferation of human fetal and adult microglia in primary cultures. AB - Proliferation of microglia/macrophages is a common finding in many central nervous system diseases. To identify mitogenic signals for human microglia, we examined primary cultures of human fetal and adult microglia after stimulation with cytokines, colony stimulating factors (CSFs), or LPS, using proliferating cell nuclear antigen (PCNA) expression as an index of cell proliferation. The results showed that both M-CSF and GM-CSF induced microglial proliferation in fetal and adult human cultures, but that GM-CSF provided a much stronger stimulus. At 96 h post-stimulation, the mean PCNA labeling index was 2.4 for M CSF and 13.3 for GM-CSF in fetal microglia; in adult microglia, the PCNA labeling index was 4.7 for M-CSF and 9.0 for GM-CSF. The effect of GM-CSF on fetal microglia was dose dependent and synergistic with M-CSF. LPS abolished the basal level of PCNA labeling in adult microglia, but in fetal microglia, caused a slight increase in PCNA labeling (1.9) at 96 h and consistently enhanced microglial cell survival and differentiation into highly branched cells. The production of GM-CSF in purified human fetal astrocyte and microglial cultures was examined after stimulation with LPS, TNF-alpha, or IL-1 beta. Unlike M-CSF, neither cell type produced GM-CSF in unstimulated cultures; however, when stimulated with IL-1 beta, astrocytes expressed GM-CSF mRNA and protein, which accumulated in the culture through 72 h. In microglia, LPS was the only effective inducing agent. An immunocytochemical study performed to identify in vivo sources of GM-CSF revealed selective labeling of reactive astrocytes in active lesions of multiple sclerosis and senile plaques of Alzheimer's disease. Our data demonstrate that both fetal and adult human microglia are capable of proliferation in response to CSFs, GM-CSF being the more effective stimulus. PMID- 7890334 TI - Glial development in primary cultures established from normal and X-irradiated neonatal spinal cord. AB - The glial population of the lumbosacral spinal cord of the rat can be markedly depleted by exposure to ionizing radiation during the first postnatal week. Identification of specific cell populations which survive the exposure to radiation is difficult in situ; therefore, the present investigation used in vitro approaches to address issues related to specific phenotypes and maturational states of glia in cultures derived from non-irradiated (control) and irradiated (experimental) lumbosacral spinal cords of 3-day-old rats. Cultures were established from the spinal cords 2 to 4 hours following irradiation and were compared to cultures from non-irradiated, littermate controls. By 4 days in vitro (DIV) the numbers of cells in experimental cultures were profoundly reduced when compared to controls, and this reduction persisted through the termination of the study (8 DIV). In addition to reduction in numbers, astrocyte phenotypes were altered in experimental cultures, with greater proportions of the astrocyte population being constituted by the flat angular, large angular, and pancake types and a lesser proportion by stellate cells. The non-astrocytic cell types were dramatically reduced as evidenced by the paucity of oligodendrocytes immunoreactive for galactocerebroside and of small, non-process bearing cells binding the lectin, Griffonia (Bandeiraea) simplicifolia, a marker for microglia. Experimental cultures contained an increased incidence of binucleate astrocytes, an increase not restricted to a particular astrocyte phenotype. This study established the feasibility of utilizing this combined in vivo/in vitro approach in assessment of glial populations in immature spinal cords, and further investigations are in progress using this model. PMID- 7890335 TI - Differences in the disposition and toxicity of 1-methyl-4-phenylpyridinium in cultured rat and mouse astrocytes. AB - Species difference in the susceptibility to 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) was investigated in cultured rat and mouse astrocytes, where 1-methyl-4-phenylpyridinium (MPP+), the toxic mediator of MPTP, is formed. Type A monoamine oxidase (MAO) predominated in both rat and mouse astrocytes, while its activity was slightly higher in mouse cells compared to rat cells; MAO B activity, on the other hand, was significantly lower in mouse astrocytes than in rat astrocytes. Because both types of MAO have been reported to make similar contributions to MPP+ production in astrocytes, their total activity was examined and results indicated that there was no significant difference between these two species. In addition, MPP+ caused a dose-dependent loss of cell viability as judged by the amount of lactate dehydrogenase released into the incubation medium. The toxicity of MPP+ on astrocytes started to be seen after a 2 day incubation period. Mouse astrocytes were more vulnerable to MPP+ than rat astrocytes. The threshold values for MPP+ toxicity in mouse and rat cultures were 10 microM and 70 microM, respectively. After addition of [3H] MPP+ to the medium, intracellular [3H] MPP+ was found to increase in both cultures. Mouse astrocytes accumulated more MPP+ than rat astrocytes (150 pmol/mg protein vs. 65 pmol/mg protein). When astrocytes were allowed to accumulate [3H] MPP+ and then incubated in fresh medium not containing [3H] MPP+, intracellular levels of [3H] MPP+ in both cells rapidly declined (110 pmol/protein in mouse vs. 40 pmol/mg protein in rat of MPP+ been released).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7890336 TI - Cultured rat astrocytes possess Na(+)-Ca2+ exchanger. AB - Na(+)-Ca2+ exchange activity in its reverse mode was demonstrated in cultured rat astrocytes. Combination of ouabain (1 mM) and monensin (20 microM) caused a marked increase in 45Ca2+ uptake in astrocytes. 45Ca2+ uptake was also stimulated by lowering the external Na+ concentration. Ouabain plus monensin-stimulated 45Ca2+ uptake was blocked by 3,4-dichlorobenzamil (IC50, 16 microM), an inhibitor of Na(+)-Ca2+ exchanger, but not by nifedipine (0.1 microM). The stimulated 45Ca2+ uptake was observed even in K(+)-free medium, and external K+ at 5-10 mM caused a 2.2-fold increase in the uptake. Microspectrofluorimetry using the Ca(2+)-sensitive dye fura-2 showed that ouabain plus monensin increased intracellular Ca2+ concentration in single astrocytes. The Ca2+ signal was dependent on external Ca2+ (EC50, 1.4 mM), and blocked by 20 microM 3,4 dichlorobenzamil, but not by Ca2+ channel blockers (Cd2+, 20 microM; Ni2+, 100 microM). Antiserum of cardiac Na(+)-Ca2+ exchanger recognized 160 and 120-135 kDa proteins on SDS-polyacrylamide gel electrophoresis of astrocyte homogenate. Northern blot analysis revealed the presence of mRNA for the exchanger protein in astrocytes. These findings indicate that Na(+)-Ca2+ exchanger which is modulated by K+ is present in cultured rat astrocytes. PMID- 7890337 TI - Medical therapy to the fetus. PMID- 7890338 TI - Neurosonographic abnormalities in neonates with hypoxic ischemic encephalopathy. AB - Pattern of neurosonographic (NSG) abnormalities in 150 term newborn infants with hypoxic ischemic encephalopathy (HIE) was studied. Sonographic abnormalities, presumably indicating cerebral edema and or ischemia, were observed in 86% (n = 129) cases. Obliteration of the ventricles occurred as the sole abnormality in 30 (20%) cases. Eighty (53%) patients had diffusely increased echogenicity of the brain parenchyma (DPE) in addition to the compression of the ventricles, sulci and the interhemispheric fissure. Focal parenchymal echodense (FPE) lesions occurred in nine (6%) neonates with HIE. Ten (6.6%) patients, however, had increased periventricular echogenicity (PVE). Two patients, one with focal parenchymal lesions and the other with PVE had obliterated ventricles in addition. Regarding temporal sequence earliest NSG abnormalities were DPE or slit like ventricles that were observed on day-1 itself. Focal or periventricular echogenic lesions, however, made their first appearance on day-3 of life. Twenty one patients had normal scans. Fifty patients with abnormal scans died. None of the infants with normal scans, however, died (p < 0.001). At 4 weeks of age, scans performed in 100 survivors revealed no abnormality in 51 cases. Others showed development of cerebral atrophy (n = 21), multicystic encephalomalacia (n = 2), porencephalic cyst (n = 1), or persistence of PVE without cystic changes (n = 4). The results of this study highlight the diagnostic efficacy of neurosonography in cases of HIE. We suggest that it should be incorporated in the routine evaluation of patients with hypoxic brain injury. PMID- 7890339 TI - Maternal hemoglobin and serum albumin and fetal growth. AB - Four hundred and eighty four pregnant women and their offsprings were studied to determine the relationship of maternal hemoglobin and serum protein levels on the birthweight of offspring. The correlation coefficient of maternal hemoglobin as well as serum albumin level (gamma = 0.1097 and 0.0936, respectively) with birthweight were not statistically significant. However, mean birthweight of neonates born to nonanemic mothers was significantly higher than of those born to anemic mothers. The prevalence of low birthweight babies was significantly higher among anemic mothers (p < 0.01); however, no such trend was observed in relation to maternal serum albumin (p > 0.05). PMID- 7890340 TI - Neonatal behavior in full-term small for date. AB - Fifty newborns, 25 full term SFDs (small for date) and 25 full term AGAs (appropriate for gestational age) were taken up for comparative study of their behavior using BNBAS (Brazelton's neonatal behavior assessment scale). The study revealed that full term SFDs performed significantly poorly on all items under cluster interactive processes compared to their counterparts full term AGAs on day 1. They also showed similar poor performance in clusters of motor processes and organizational processes (State control). Follow up assessment on day 30 revealed significantly better performance in these clusters. However, the performance of SFD babies in all items of cluster of organizational processes (physiological response) was comparable to that of AGA babies in the initial as well as follow up assessments. PMID- 7890341 TI - Stroke in children in Yaounde, Cameroon. AB - Thirty five children aged 5 months to 15 years suffering from stroke were studied from August 1984 to July 1990 from two hospitals in order to determine the incidence, the etiological factors and the short term outcome of the stroke. The average annual incidence was 1.85 per 1000 pediatric hospitalizations. There was a progressive rise in the number of cases from 1985, with a peak in 1990. Motor impairment of one half of the body was the commonest clinical feature seen in 97.1% of the cases. Other clinical signs were: facial paralysis (62.9%) and aphasia (28.6%). The main etiological factors were: homozygous sickle cell disease (31.4%), heart disease (17.1%), cerebral malaria (14.3%) and meningitis (14.3%). No causative factor was identified in 7 patients (20%). The mortality rate was low (2.9%) and all the children had neurological deficit after a mean hospital stay of 15 days. Laboratory investigations including lipid analysis, platelet count, and skull X-rays proved to be of no diagnostic value. However, computed tomography (CT) scan confirmed the diagnosis of ischemic stroke whenever it could be done. PMID- 7890342 TI - Childhood myelodysplasia. AB - The clinical data and hematological features of 29 children, under the age of 12 years, with primary myelodysplasia are presented. The diagnosis was made using the FAB (French-American-British) Cooperative Group criteria. There were 24 males and 5 females aged 4 months to 12 years (median 2.5 years) with marked male preponderance. Childhood myelodysplasia constituted 16% of all hematological malignancies and 36.7% of acute myeloid leukemias. The median duration of symptoms prior to diagnosis was 3 months. There were 15 cases of refractory anemia, one of refractory anemia with excess blasts, 3 of refractory anemia with excess blasts in transformation and 10 cases of chronic myelomonocytic leukemia. Five patients evolved to acute myeloid and 4 to acute lymphatic leukemia. The median duration of preleukemic phase in these patients was 7 months (range 4-29 months). The overall mean survival was short (5-9 months) in all the subgroups. Besides supportive therapy in most patients, two patients were treated with etoposide, one with alfa interferon 2b and one with high dose methylprednisolone. Our results show that myelodysplasia is not infrequent in children. The disease has an aggressive clinical course and may evolve into acute leukemia. PMID- 7890343 TI - Hepatic manifestations in typhoid fever. AB - Thirty one children with typhoid fever aged 2 months to 12 years and blood culture positive for multidrug resistant S. typhi were prospectively studied for their hepatic functions at the time of hospitalization and 2-3 weeks after completion of antibiotic therapy. Hepatic manifestations included hepatomegaly (51.6%); jaundice (16.1%); raised levels of serum glutamic oxaloacetic transaminase (SGOT) (61.3%), serum glutamic pyruvic transaminase (SGPT) (48.4%), alkaline phosphatase (AP) (22.6%) and serum bilirubin (SB) (6.1%); reduced levels of serum albumin (SA) (41.9%); prolonged prothrombin time (PT) (9.7%) and abnormal ultrasound abdomen (19.3%). Hepatic dysfunction was a notable feature even in those cases without hepatomegaly, with raised levels of SGOT (60%), SGPT (40%), AP (20%), SB (6.7%), decreased SA (53.3%) and prolonged PT (6.7%). There was no correlation between the degree of hepatic enlargement or hyperbilirubinemia with abnormalities in liver functions. Hepatic dysfunction was noticed to be transient, as all these parameters returned to normal within 2-3 weeks after successful antibiotic therapy. PMID- 7890344 TI - Enteric fever: a changing perspective. AB - All the cases of enteric fever admitted between 1988-1992 were studied. There was a gradual rise in the number of admitted cases. Central nervous system (CNS) complications like encephalopathy (14.9%), meningitis (8.8%), seizures (8.5%) and cerebellitis (3.4%) were noted more during 1991 and 1992. Other complications like myocarditis (4.6%), hepatitis (9.5%) and gastrointestinal bleeding were noted in increasing numbers during 1991-1992. Multidrug resistant (MDRT) cases were 46.3% in 1991 and 33.5% in 1992. There was a significant difference in the time taken for defervescence (a gradual rise) between the years but between the individual drugs there was no such significant difference. Deaths were noted only in 1991 and 1992 in cases of MDRT with complications. There has been an increase in resistance of S. typhi to commonly used drugs like ampicillin, chloramphenicol and cotrimoxazole. S. typhi resistant to ciprofloxacin was cultured in 2 cases each from 1990-1992. Further, the time taken for defervescence with ciprofloxacin also showed a gradual rise from 3.5 days in 1990 to 6.2 days in 1992. Nevertheless, ciprofloxacin is still the drug of choice for treatment of complicated cases of MDRT. PMID- 7890345 TI - Complicated falciparum malaria. AB - We studied 50 cases of complicated falciparum malaria in order to evaluate the different clinical presentations. Thirty five had cerebral malaria while 15 presented with extracerebral features including diarrhea and vomiting (n = 6), hepatitis (n = 4), acute renal failure (n = 3), and gastrointestinal bleeding (n = 2). These cases were treated with quinine. Mortality was higher in extracerebral form (33.3%) as compared to cerebral malaria (22%). Our study suggests that even though cerebral malaria remains the single most important cause of high mortality in complicated falciparum malaria, extracerebral presentation of falciparum malaria is equally life threatening and should be viewed seriously. PMID- 7890346 TI - Age at menarche and first conception in sickle cell hemoglobinopathy. AB - Sickle cell hemoglobinopathy has emerged as a major public health problem in the tropical countries of the world including India. This paper deals with the age at menarche and first conception of women in relation to sickle cell genotypes. The mean age at menarche was slightly higher in sickle cell affected girls compared to controls. The delay in onset of menarche affects the age at first conception of the sickle cell afflicted individuals. PMID- 7890347 TI - Perinatal mortality in Shimla (Himachal Pradesh) PMID- 7890349 TI - Consumption coagulopathy in neonates born to mothers with pregnancy induced hypertension. PMID- 7890348 TI - Birth weight pattern in Karnataka. PMID- 7890350 TI - Unusual presentation in early congenital syphilis. PMID- 7890351 TI - Spontaneous aortic thrombosis in a neonate. PMID- 7890352 TI - Declining trend in tetanus hospitalizations. PMID- 7890353 TI - Serum vitamin E in cord blood and early neonatal period. PMID- 7890354 TI - Glycolytic enzymes in beta-thalassemia. PMID- 7890355 TI - Poisoning with writing ink. PMID- 7890356 TI - Relactation. PMID- 7890357 TI - What is the appropriate time for BCG vaccination in preterm infants? PMID- 7890358 TI - Sprengel's deformity. PMID- 7890359 TI - Dopamine infusion: a simpler formula. PMID- 7890360 TI - Non-01 Vibrio cholerae. PMID- 7890361 TI - Apert syndrome with partial post-axial polydactyly and unilateral choanal atresia. PMID- 7890362 TI - Bladder stone presenting as excessive masturbation. PMID- 7890364 TI - Diagnostic approach to a child with mental retardation. PMID- 7890363 TI - Successful treatment with cyclophosphamide in a large hepatic hemangioendothelioma. PMID- 7890365 TI - Effect of experimental influenza A virus infection on isolation of Streptococcus pneumoniae and other aerobic bacteria from the oropharynges of allergic and nonallergic adult subjects. AB - Intranasal challenge with both influenza A virus and Streptococcus pneumoniae promotes otitis media with S. pneumoniae in chinchillas. We investigated whether influenza A virus infection promotes oropharyngeal colonization with S. pneumoniae and other middle ear pathogens by selectively inhibiting commensal bacteria. On study day 0, 12 allergic and 15 nonallergic adult subjects were intranasally inoculated with influenza A/Kawasaki (H1N1) virus. Every subject was infected with the virus as demonstrated by nasal shedding or seroconversion. Average upper respiratory symptom scores and nasal secretion weights from the entire subject group were elevated between days 2 and 6 (acute phase) and were not significantly different between allergic and nonallergic subjects. S. pneumoniae was not isolated from any subject prior to the virus challenge but was isolated in heavy density from 4 (15%) subjects on day 6 (P = 0.055). Staphylococcus aureus was isolated more frequently from the nonallergic subjects than from the allergic subjects on days 2 (80 versus 25%, respectively) 4, (67 versus 17%, respectively), and 6 (73 versus 25%, respectively) (P < 0.05). The isolation rates of other middle ear pathogens were not significantly different before virus challenge and during the acute and resolution phases (days 27 to 30) of the experimental infection for the entire subject group or either the allergic or nonallergic subgroup. Densities and isolation rates of commensal bacteria from the entire subject group were similar throughout the observational period. These results suggest that the virus infection promoted S. pneumoniae colonization of the oropharynx and that nonallergic persons may be more vulnerable to colonization with S. aureus than allergic persons. The altered colonization rates were not attributed to inhibition of commensal bacteria. PMID- 7890366 TI - Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D galactosamine-sensitized and unsensitized mice. AB - Administration of staphylococcal enterotoxin B (SEB) to BALB/c mice was found to induce a cytokine release syndrome hallmarked by weight loss and hypoglycemia. A neutralizing monoclonal antibody against gamma interferon (IFN-gamma) given before SEB counteracted weight loss and prevented hypoglycemia. This protective effect of anti-IFN-gamma antibody was associated with decreased IFN-gamma levels in serum; tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels remained unchanged. A monoclonal anti-IL-6 antibody, known for its ability to cause accumulation of biologically active IL-6 in the circulation, did not modify SEB induced body weight loss or hypoglycemia. Levels of TNF, IFN-gamma, and IL-6 in serum were all more elevated in anti-IL-6-treated mice than in corresponding SEB challenged control mice. In D-galactosamine-sensitized mice, SEB-induced weight loss but not hypoglycemia was more severe, resulting mostly in death within 24 h. Higher levels of biologically active TNF and IFN-gamma in serum were noted in these mice than in mice receiving SEB only. In D-galactosamine-sensitized mice, anti-IFN-gamma antibody did prevent hypoglycemia but failed to reduce the severity of the syndrome. Again, TNF levels in anti-IFN-gamma-treated mice remained unchanged. Pretreatment with anti-IL-6 antibody temporarily attenuated SEB-induced hypoglycemia in sensitized mice. Thus, at 6 h post-SEB injection, anti-IL-6-treated mice were less hypoglycemic than corresponding controls. However, at 24 h, hypoglycemia was significantly aggravated. Concomitantly, IL-6 levels were dramatically increased. Neither anti-IFN-gamma nor anti-IL-6 antibody treatment modulated mortality levels in D-galactosamine-sensitized mice. The data obtained with anti-IFN-gamma antibody clearly indicate that endogenous IFN-gamma is instrumental in bringing about hypoglycemia and body weight loss in mice exposed to SEB but also that hypoglycemia is not a crucial determinant of mortality in D-galactosamine-sensitized mice. The data obtained with anti-IL-6 antibody indicate that endogenous IL-6 is involved in regulating the levels of TNF and IFN-gamma in serum. PMID- 7890367 TI - Endogenous gamma interferon, tumor necrosis factor, and interleukin-6 in Staphylococcus aureus infection in mice. AB - The production and roles of endogenous gamma interferon (IFN-gamma), tumor necrosis factor (TNF), and interleukin-6 (IL-6) in both lethal and nonlethal infections of Staphylococcus aureus were investigated in mice. In the case of nonlethal infection, although no bacteria were detected in the bloodstreams, bacteria that colonized and proliferated persistently for 3 weeks were found in the kidneys. All mice given lethal injections died within 7 days, and large numbers of bacteria were detected in the bloodstreams, spleens, and kidneys. The first peaks of IFN-gamma, TNF, and IL-6 were observed in the bloodstreams and spleens of the mice with nonlethal and lethal infections within 24 h. Thereafter, in the nonlethal cases, IFN-gamma, TNF, and IL-6 peaked again in the spleens and kidneys during the period of maximum growth of bacteria in the kidneys, although only IL-6 was detected in the sera. In contrast, in the case of lethal infection, the titers of IFN-gamma and IL-6 in the sera and TNF in the kidneys peaked before death. Effects of in vivo administration of monoclonal antibodies (MAbs) against IFN-gamma and TNF on the fates of S. aureus-infected mice were studied. In the nonlethal infections, anti-TNF alpha (anti-TNF-alpha) MAb-treated mice, but not anti-IFN-gamma MAb-treated mice, died as a result of worsening infection, suggesting that endogenous TNF plays a protective role in host resistance to S. aureus infection. In the mice that received lethal doses, injection of anti-TNF alpha MAb accelerated death. However, although injection of anti-IFN-gamma MAb inhibited host resistance of the infected mice early in infection, most of the animals survived the lethal infection by injection of anti-IFN-gamma MAb, suggesting that endogenous IFN-gamma plays a detrimental role in S. aureus infection. Thus, this study demonstrated that IFN-gamma and TNF play different roles in S. aureus infection. PMID- 7890368 TI - Strain variation in tumor necrosis factor induction by parasites from children with acute falciparum malaria. AB - A small proportion of individuals infected with Plasmodium falciparum develop cerebral malaria. Why it affects some infected individuals but not others is poorly understood. Since tumor necrosis factor (TNF) has been implicated strongly in the pathogenesis of cerebral malaria, here we have compared different parasite isolates for their ability to induce TNF production by human mononuclear cells in vitro. Wild isolates were collected from 34 Gambian children with cerebral malaria and 66 children with uncomplicated malaria fever. Cerebral malaria isolates tended to stimulate more TNF production than mild malaria isolates, but there was considerable overlap between the two groups, and the present data provide only limited support for the hypothesis that cerebral malaria is caused by strains of P. falciparum inducing high levels of TNF. However, it is notable that the amounts of TNF induced by different wild isolates from a single locality differed by over 100-fold. The biological significance of this polymorphism deserves further scrutiny in view of the central role that TNF is believed to play in host defense and in the clinical symptomatology of human malaria. PMID- 7890369 TI - The multiple forms of trypsin-like activity present in various strains of Porphyromonas gingivalis are due to the presence of either Arg-gingipain or Lys gingipain. AB - Porphyromonas gingivalis contains high concentrations of numerous cysteine proteinases with trypsin-like activity which have been implicated as important virulence factors in adult-onset periodontitis. We have analyzed the subfractions of six P. gingivalis strains for the presence of arginine-X- and lysine-X specific proteinases (Arg-gingipain [RGP] and Lys-gingipain [KGP]) previously purified from P. gingivalis H66. Western blot (immunoblot) analysis using antibodies produced against RGP and the N-terminal peptides of RGP or the catalytic subunit of KGP indicated that these enzymes are synthesized by the strains studied and exist as multiple molecular mass species. The major forms of RGP were identified as 110-, 95-, 70- to 90-, and 50-kDa proteins, the first two being a complex of the 50-kDa catalytic subunit with hemagglutinins, with or without an added membrane anchorage peptide. The other forms are single-chain enzymes. While the 95- and 50-kDa RGP were found predominantly in culture medium, the 110- and 70- to 90-kDa forms associated with membranous fractions of the bacteria. The predominant form of KGP in all strains was a complex of the 60-kDa catalytic domain with hemagglutinins, and vesicle- and membrane-associated KGP was about 15 kDa larger than the 105-kDa enzyme present in culture media. These data explain the apparent complexity of P. gingivalis proteinases and indicate that in all strains tested there are two identical enzymes, one with arginine-X specificity and the other with lysine-X specificity, which, working in concert, are responsible for the trypsin-like activity associated with this bacterium. PMID- 7890370 TI - Activation of human THP-1 cells and rat bone marrow-derived macrophages by Helicobacter pylori lipopolysaccharide. AB - The mechanism by which Helicobacter pylori, which has little or no invasive activity, induces gastric-tissue inflammation and injury has not been well characterized. We have previously demonstrated that water-extracted proteins of H. pylori are capable of activating human monocytes by a lipopolysaccharide (LPS) independent mechanism. We have now compared activation of macrophages by purified LPS from H. pylori and from Escherichia coli. LPS was prepared by phenol-water extraction from H. pylori 88-23 and from E. coli O55. THP-1, a human promyelomonocytic cell line, and macrophages derived from rat bone marrow each were incubated with the LPS preparations, and cell culture supernatants were assayed for production of tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2), and nitric oxide. THP-1 cells showed maximal activation by the LPS molecules after cell differentiation was induced by phorbol 12-myristate 13 acetate. Maximal TNF-alpha and PGE2 production occurred by 6 and 18 h, respectively, in both types of cells. In contrast, NO was produced by rat bone marrow-derived macrophages only and was maximal at 18 h. The minimum concentration of purified LPS required to induce TNF-alpha, PGE2, and NO responses in both types of cells was 2,000- to 30,000-fold higher for H. pylori than for E. coli. Purified LPS from three other H. pylori strains with different polysaccharide side chain lengths showed a similarly low level of activity, and polymyxin B treatment markedly reduced activity as well, suggesting that activation was a lipid A phenomenon. These results indicate the low biological activity of H. pylori LPS in mediating macrophage activation. PMID- 7890371 TI - Binding, oligomerization, and pore formation by streptolysin O in erythrocytes and fibroblast membranes: detection of nonlytic polymers. AB - Streptolysin O (SLO) is a representative of the family of cholesterol-binding cytolysins that form large pores in target cell membranes. Aggregation of the toxin to polymeric structures is required for pore formation. However, it is not known whether, vice versa, polymers may under certain circumstances remain nonfunctional, and whether this might be the cause underlying the relative resistance of certain cells towards toxin action. In the present study, we applied radioiodinated, functionally active SLO to human, rabbit, and mouse erythrocytes and to human fibroblasts and keratinocytes. Binding and polymerization were quantified and correlated with membrane damage. At low toxin concentrations, human and rabbit but not mouse erythrocytes were lysed, but binding and polymerization of SLO were essentially identical in all cases. Nonlytic polymers were also detected on human fibroblasts and keratinocytes treated with subcytotoxic concentrations of SLO, and quantitative estimates indicated that nonpermeabilized cells could carry hundreds of polymers on their surface. When applied at low concentrations to fibroblasts, much of the toxin remained in monomer form and was subsequently shed from the cells. This was shown by monitoring the fate of radioiodinated toxin and also by using a sensitive cell enzyme-linked immunosorbent assay that permitted immunological detection of surface-exposed SLO. Thus, relative resistance of cells towards the permeabilizing action of SLO may be due to their ability to tolerate formation of a limited number of SLO polymers and to shedding of nonoligomerized toxin from their surface. PMID- 7890372 TI - Adjuvanticity and protective immunity elicited by Bordetella pertussis antigens encapsulated in poly(DL-lactide-co-glycolide) microspheres. AB - Purified Bordetella pertussis antigens, encapsulated in biodegradable poly(DL lactide-co-glycolide) (DL-PLG) microspheres, were evaluated for their immunogenicity and ability to elicit a protective immune response against B. pertussis respiratory infection. Microencapsulated pertussis toxoid, filamentous hemagglutinin, and pertactin all retained their immunogenicity when administered parenterally. Intranasal immunization with a low dose (1 micrograms) of encapsulated filamentous hemagglutinin, pertussis toxoid, or pertactin elicited strong specific immunoglobulin G and immunoglobulin A antibody responses in respiratory secretions that were greater in magnitude than the responses elicited by the same doses of unencapsulated antigen. Intranasal immunization with as little as 1 micrograms of encapsulated pertussis antigen prior to infection reduced the bacterial recovery by 3 log10 CFU. However, intranasal immunization with the same low doses of unencapsulated antigens did not reduce infection. Intranasal administration of a combination of 1 micrograms of each of the microencapsulated pertussis antigens was more effective in reducing bacterial infection than administration of any single microencapsulated antigen. Intranasal administration of microencapsulated B. pertussis antigens elicits high levels of specific antibody coinciding with protection against infection when these microspheres are administered to the respiratory tract. These data provide evidence of the respiratory adjuvanticity of three different DL-PLC microsphere preparations, each of which contains a unique B. pertussis antigen. PMID- 7890373 TI - Identification and characterization of genes encoding the human transferrin binding proteins from Haemophilus influenzae. AB - Haemophilus influenzae, a strict human pathogen, acquires iron in vivo through the direct binding and removal of iron from human transferrin by an as yet uncharacterized process at the bacterial cell surface. In this study, the tbpA and tbpB genes of H. influenzae, encoding the transferrin-binding proteins Tbp1 and Tbp2, respectively, were cloned and sequenced. Alignments of the H. influenzae Tbp1 and Tbp2 protein sequences with those of related proteins from heterologous species were analyzed. On the basis of similarities between these and previously characterized proteins, Tbp1 appears to be a member of the TonB dependent family of outer membrane proteins while Tbp2 is lipid modified by signal peptidase II. Isogenic mutants deficient in expression of Tbp1 or Tbp2 or both proteins were prepared by insertion of the Tn903 kanamycin resistance cassette into cloned sequences and reintroduction of the interrupted sequences into the wild-type chromosome. Binding assays with the mutants showed that a significant reduction in transferrin-binding ability resulted from the loss of either of the Tbps and a complete loss of binding was evident when neither protein was expressed. Loss of either Tbp2 or both proteins correlated with an inability to grow on media supplemented with transferrin-bound iron as the sole source of iron, whereas the Tbp1+ Tbp2- mutant was able to grow only at high transferrin concentrations. PMID- 7890374 TI - Expansion of mycobacterium-reactive gamma delta T cells by a subset of memory helper T cells. AB - Human gamma delta T cells expressing the V gamma 9/V delta 2 T-cell receptor have been previously found to proliferate in response to certain microorganisms and to expand throughout life, presumably because of extrathymic activation by foreign antigens. In vitro expansion of V gamma 9/V delta 2 cells by mycobacteria has been previously shown to be dependent on accessory cells. In order to gain an insight into the mechanisms involved in the expansion of these cells, we have undertaken to identify the peripheral blood subset of cells on which proliferation of V gamma 9/V delta 2 cells in response to mycobacteria is dependent. Contrary to their role in antigen presentation to alpha beta T cells, professional antigen-presenting cells, such as monocytes, B cells, and dendritic cells, were unable to provide the cellular support for the expansion of V gamma 9/V delta 2 cells. Selective depletion of T-cell subsets, as well as the use of highly purified T-cell populations, indicated that the only subset of peripheral blood cells that could expand V gamma 9/V delta 2 cells were CD4+ CD45RO+ CD7- alpha beta T cells. These cells underwent distinct intracellular signaling events after stimulation with the mycobacterial antigen. Expansion of V gamma 9/V delta 2 cells by alpha beta T cells was dependent on cell-cell contact. This is the first evidence that a small subset of the memory helper T-cell population is exclusively responsible for the peripheral expansion of V gamma 9/V delta 2 cells. These data illustrate a unique aspect of antigen recognition by gamma delta T cells and provide new means to study their immune defense role. PMID- 7890375 TI - Biomolecular events involved in anticryptococcal resistance in the brain. AB - We have recently shown that intracerebral (i.c.) administration of heat-killed Cryptococcus neoformans (HCN) enhances mouse resistance to a subsequent local challenge with lethal doses of viable yeast cells. Here we show that i.c. administration of HCN is also effective in significantly delaying brain colonization of mice intravenously infected with viable C. neoformans. PCR analysis revealed that interleukin 6 (IL-6) and IL-1 beta gene expression occurs in brain of HCN-treated mice but not in brains of saline-treated controls. In contrast, no differences are observed in terms of tumor necrosis factor alpha and IL-1 alpha gene transcripts, which are slightly and highly detectable, respectively, in saline-treated mice and which remain such also following HCN treatment. Furthermore, i.c. administration of exogenous IL-6 or IL-1 beta, but not tumor necrosis factor alpha, before local challenge with viable C. neoformans results in significantly reduced microbial counts in the brain and blood and in increased mouse survival. Taken together, these observations provide initial evidence that brain anticryptococcal resistance involves elicitation of a local cytokine response, involving primarily IL-6 and IL-1 beta. PMID- 7890376 TI - In vitro modulation of keratinocyte-derived interleukin-1 alpha (IL-1 alpha) and peripheral blood mononuclear cell-derived IL-1 beta release in response to cutaneous commensal microorganisms. AB - The ability of a range of skin commensal microorganisms to modulate interleukin-1 (IL-1) release by cultured human keratinocytes and peripheral blood mononuclear cells (PBMCs) was investigated by a combination of enzyme-linked immunosorbent assays and bioassays. Three fractions (formaldehyde-treated whole cells, culture supernatants, and cellular fractions) were prepared from Propionibacterium acnes, Propionibacterium granulosum, Staphylococcus epidermidis, Staphylococcus capitis, Staphylococcus hominis, and Malassezia furfur serovar B. The levels of immunochemical IL-1 alpha released by cultured keratinocytes during coincubations with these microbial fractions ranged from 0 to 136 pg/ml and were maximal after 72 h. No microbial fraction consistently upregulated immunochemical IL-1 alpha release by freshly isolated keratinocytes from two donors and a transformed cell line, all of which produced the cytokine constitutively to various extents. Bioassays revealed that most of the IL-1 released was biologically inactive. In contrast, whole cells of formaldehyde-treated P. granulosum and S. epidermidis significantly stimulated release of IL-1 beta by PBMCs from three donors compared with the negative control (culture medium). Release was maximal at 24 h. Coincubation with intact cells of the yeast M. furfur significantly decreased levels of IL-1 beta below the values for the negative control by PBMCs from all three donors. There was good correlation between bioassay data and immunoassay data for IL-1 beta, and the depressive effect of M. furfur cells on cytokine production by all three cultures of PBMCs was mirrored in the levels of bioactive cytokine. This reduction in IL-1 beta release by PBMCs by M. furfur may provide an explanation why dermatoses thought to be caused by this yeast are essentially noninflammatory or only mildly inflammatory. PMID- 7890377 TI - Biological activity of toxic shock syndrome toxin 1 and a site-directed mutant, H135A, in a lipopolysaccharide-potentiated mouse lethality model. AB - A recombinant of toxic shock syndrome toxin 1 (TSST-1) which contains a single histidine-to-alanine mutation at residue 135 (H135A) was analyzed for toxicity and vaccine potential in a lipopolysaccharide (LPS)-potentiated mouse lethality model. The 50% lethal dose (LD50) of TSST-1 in BALB/c mice was 47.2 micrograms/kg, but H135A was not lethal when tested at a dose equivalent to 10 LD50s of TSST-1. Levels of tumor necrosis factor (TNF) and gamma interferon (IFN gamma) in serum were, respectively, 10- and 50-fold higher in LPS-potentiated mice injected with 15 LD50s of TSST-1 than in mice given H135A. Mice injected with only TSST-1 did not have elevated levels of TNF or IFN-gamma in serum, while H135A plus LPS or LPS alone elicited identical, yet very low, levels of TNF and IFN-gamma. An enzyme-linked immunosorbent assay of H135A and TSST-1 with anti TSST-1 serum yielded very similar dose-response curves, which strongly suggests that H135A serologically and conformationally resembles the native toxin. Mice immunized with H135A developed antibodies that recognized TSST-1 in an enzyme linked immunosorbent assay and afforded protection against a 15-LD50 challenge of TSST-1 plus LPS. The pooled sera of mice immunized with either TSST-1 or H135A also prevented lymphocyte proliferation due to TSST-1. PMID- 7890378 TI - Lymphocyte populations during tuberculosis infection: V beta repertoires. AB - The immune response to Mycobacterium tuberculosis is mediated by T lymphocytes. We studied the changes in lymphocyte populations occurring in peripheral blood, pleural fluid, and ascites during tuberculosis infection. For this purpose, we compared recent-onset patients (newly converted to positive Mantoux reactions) with previously diagnosed patients (individuals with organic lesions). Recent infection was associated with peripheral blood lymphocytosis involving T lymphocytes expressing either T-cell receptor alpha/beta or gamma/delta. Lymphocytosis involved both CD4 and CD8 cells. On the other hand, we detected no changes in the distribution of peripheral blood lymphocyte populations in previously diagnosed patients. No changes were found in the numbers of B lymphocytes or natural killer cells in either recently infected or previously diagnosed patients. The pleural effusion and ascitic fluid samples contained T lymphocytes expressing T-cell receptor alpha/beta, the majority of which were CD4+. These lymphocytes showed an inverted CD45RA-to-CD45RO ratio, and we found high-level expression of the interleukin-2 receptor (CD25) in some patients. The results are compatible with the existence of periods of cell activation in the pleural fluid (which are disclosed by the appearance of the CD25 antigen and the transition of CD45RA expression to CD45RO) together with nonactivation periods (loss of CD25 and persistence of CD45RO expression). We studied a fraction of the V beta repertoire in peripheral blood in both groups and the same fraction of the V beta repertoire in pleural fluid from patients with tuberculous pleuritis, demonstrating that, in recently infected subjects, lymphocytosis was produced by the increase in lymphocytes which expressed some specific V beta subfamilies that differed from one individual to another. In two of five patients studied, we found significant changes in the V beta repertoire between lymphocytes from peripheral blood and the pleural fluid samples. PMID- 7890379 TI - Identification and purification of a conserved heme-regulated hemoglobin-binding outer membrane protein from Haemophilus ducreyi. AB - A hemoglobin-binding protein (HgbA) from Haemophilus ducreyi was identified and purified. The 100-kDa HgbA was detected in all strains of H. ducreyi tested, and a somewhat larger hemoglobin-binding protein was found in one strain of Haemophilus influenzae. HgbA was purified and the amino acid sequence of the N terminus of HgbA revealed no significant homologies with known proteins. Two different antisera to HgbA from H. ducreyi 35000 recognized HgbA proteins from all tested H. ducreyi strains; they did not recognize proteins from the H. influenzae strain. Expression of HgbA was regulated by the level of heme but not by iron present in the medium. Animal species of hemoglobin competed with iodinated human hemoglobin for binding to whole cells of H. ducreyi and supported the growth of H. ducreyi. The lack of immunological cross-reactivity and the differences in hemoglobin specificities between the H. ducreyi and the H. influenzae hemoglobin-binding proteins suggest that they are unrelated. PMID- 7890380 TI - Effect of oral immunization with recombinant urease on murine Helicobacter felis gastritis. AB - The ability of oral immunization to interfere with the establishment of infection with Helicobacter felis was examined. Groups of Swiss Webster mice were immunized orally with 250 micrograms of Helicobacter pylori recombinant urease (rUrease) and 10 micrograms of cholera toxin (CT) adjuvant, 1 mg of H. felis sonicate antigens and CT, or phosphate-buffered saline (PBS) and CT. Oral immunization with rUrease resulted in markedly elevated serum immunoglobulin G (IgG), serum IgA, and intestinal IgA antibody responses. Challenge with live H. felis further stimulated the urease-specific intestinal IgA and serum IgG and IgA antibody levels in mice previously immunized with rUrease but activated primarily the serum IgG compartment of PBS-treated and H. felis-immunized mice. Intestinal IgA and serum IgG and IgA anti-urease antibody responses were highest in rUrease immunized mice at the termination of the experiment. Mice immunized with rUrease were significantly protected (P < or = 0.0476) against infection when challenged with H. felis 2 or 6 weeks post-oral immunization in comparison with PBS-treated mice. Whereas H. felis-infected mice displayed multifocal gastric mucosal lymphoid follicles consisting of CD45R+ B cells surrounded by clusters of Thy1.2+ T cells, gastric tissue from rUrease-immunized mice contained few CD45R+ B cells and infrequent mucosal follicles. These observations show that oral immunization with rUrease confers protection against H. felis infection and suggest that gastric tissue may function as an effector organ of the mucosal immune system which reflects the extent of local antigenic stimulation. PMID- 7890381 TI - Differential susceptibility of yeast and hyphal forms of Candida albicans to proteolytic activity of macrophages. AB - The dimorphic transition of Candida albicans from the yeast (Y-Candida) to the hyphal (H-Candida) form is a complex event whose relevance in fungal pathogenicity is still poorly understood. Using a cloned macrophage (M phi) cell line (ANA-1), we have previously shown that a M phi can discriminate between the two fungal forms, eliciting different secretory responses. In the present study, we investigated the susceptibility of Y-Candida and H-Candida to M phi proteolytic activity. In particular, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) techniques were employed to analyze the patterns of lyticase proteinaceous extracts from cell walls of Y-Candida and H-Candida which had been unexposed or exposed to ANA-1 M phis for 3 h. Silver staining allowed detection of a complex protein pattern in both forms of C. albicans, qualitatively and quantitatively differing from each other, mainly at molecular masses below 106 kDa. Western blot staining with anti-C. albicans mannan antibodies and convalescent-phase sera of mice previously infected systemically or intracerebrally with C. albicans showed that, after contact with M phis, Y-Candida but not H-Candida proteinaceous cell wall components are profoundly modified, with substantial reduction and/or disappearance of many bands. Our experimental approach provides initial insights into the differential susceptibility of Y-Candida and H-Candida to the proteolytic activity of M phis. PMID- 7890382 TI - Parasite strain specificity of precursor cytotoxic T cells in individual animals correlates with cross-protection in cattle challenged with Theileria parva. AB - Class I major histocompatibility complex-restricted parasite-specific cytotoxic T lymphocytes (CTL) are known to be a major component of the bovine immune response to the protozoan parasite Theileria parva, but formal proof for their role in protection of cattle against infection with T. parva has been lacking. Animals immunized with one stock of T. parva show variations in the degree of protection against heterologous challenge and also in the parasite strain specificity of their CTL responses. The present study investigated the relationship of strain specificity of CTL responses and cross-protection in an effort to verify the role of CTL in protection. The parasite strain specificity of the CTL responses generated in 23 cattle immunized with either of two immunologically distinct parasite populations was examined, and the susceptibility of individual cattle to challenge with the heterologous parasite population was determined. The frequency of stock-specific or cross-reactive CTL precursor cells (CTLp) in individual animals was measured by a limiting-dilution microassay. A proportion of animals immunized with either parasite exhibited cross-reactive CTLp, whereas CTLp detected in the remaining animals were specific for the homologous parasite. On challenge with the heterologous stock, those animals with cross-reactive CTLp were solidly protected while those with strain-specific CTLp showed moderate to severe reactions, although many of them recovered. The finding of a close association between strain specificity of the CTL response and protection against challenge provides strong evidence that CTL are important in mediating immunity. PMID- 7890383 TI - Loss of the O4 antigen moiety from the lipopolysaccharide of an extraintestinal isolate of Escherichia coli has only minor effects on serum sensitivity and virulence in vivo. AB - The O-specific antigen in extraintestinal isolates of Escherichia coli is believed to be an important virulence factor. To assess its role in the pathogenic process, proven isogenic derivatives with either a complete (CP921) or nearly complete (CP920) deficiency of the O4 antigen were obtained by TnphoA'1 mediated transposon mutagenesis of an O4/K54/H5 blood isolate (CP9). By utilizing a previously reported isogenic K54 capsule-deficient derivative (CP9.137), additional isogenic derivatives deficient in both the K54 capsular antigen and either all (CP923) or nearly all (CP922) of the O4 antigen were also constructed. These strains and their wild-type parent were evaluated in vitro for serum sensitivity and in vivo by intraperitoneal challenge of outbred mice. The complete or nearly complete loss of the O4 antigen (CP920 and CP921) resulted in only a minor increase in serum sensitivity. In contrast, CP9.137 had a significant increase in serum sensitivity, and CP922 and CP923 were extremely serum sensitive. When tested in vivo, the complete or nearly complete loss of the O4 antigen resulted in a small but significant increase (P < or = 0.05), not the expected decrease, in virulence compared with its wild-type parent. In contrast, CP9.137 and CP922 were significantly less virulent (P < or = 0.05). These studies do not exclude a role for the O4 antigen moiety of lipopolysaccharide in the pathogenesis of extraintestinal E. coli infection; however, they demonstrate that the O4 antigen plays only a minor role in serum resistance in vitro and that its loss does not diminish and perhaps enhances the virulence of CP9 in vivo after intraperitoneal challenge. PMID- 7890384 TI - Bacterial evasion of host immune defense: Yersinia enterocolitica encodes a suppressor for tumor necrosis factor alpha expression. AB - The ability of the enteropathogenic Yersinia enterocolitica to survive and proliferate in host tissue depends on a 70-kb plasmid known to encode a number of released Yersinia outer proteins that act as virulence factors by inducing cytotoxicity and inhibiting phagocytosis. This study demonstrates that one of the Yersinia outer proteins, the 41-kDa YopB, suppresses the production of tumor necrosis factor alpha (TNF-alpha), a macrophage-derived cytokine with central roles in the regulation of immune and inflammatory responses to infection. This conclusion is based on several lines of evidence. First, in macrophage cultures, suppression of TNF-alpha mRNA expression was induced by culture supernatant (CS+) of plasmid-bearing yersiniae, the effect which was blocked by anti-YopB antiserum. Second, suppression of TNF-alpha production, but not of interleukin-1 (IL-1) and IL-6, was induced by purified YopB. Third, in Yersinia-infected mice, no increase in TNF-alpha mRNA expression was observed in Peyer's patches, the primary site of bacterial invasion, compared with IL-1 (alpha and beta) mRNA. Finally, administration of anti-YopB antiserum to mice prior to infection with Y. enterocolitica increased TNF activity levels in Peyer's patches and coincided with a reduction in bacterial growth. The results thus provide direct evidence for a secreted eubacterial virulence factor that mediates selective suppression of TNF-alpha production. Although suppression of this single cytokine response is probably not sufficient to facilitate survival of the infecting organisms, the results suggest that suppression of TNF-alpha production by YopB significantly contributes to the evasion of Y. enterocolitica from antibacterial host defense. PMID- 7890385 TI - Role of Pseudomonas aeruginosa pili in acute pulmonary infection. AB - The role of piliation in the development and course of acute pulmonary infection was examined using infant BALB/cByJ mice inoculated by intranasal instillation of isogenic Pil+ and Pil- mutants of Pseudomonas aeruginosa PA1244, PAK, and PAO1. The piliated strains caused more cases of pneumonia, bacteremia, and mortality than the nonpiliated strains (chi-square analysis, alpha = 0.001). The piliated strains were more often associated with severe diffuse pneumonias, while the nonpiliated organisms resulted in less severe, focal pneumonias, although these differences did not achieve statistical significance. Purified pilin protein used to inoculate the mice resulted in local inflammatory changes. The nonpiliated strain PA1244-NP was as virulent as the piliated strain PAO1, suggesting that expression of other virulence factors are also important in the development of acute pneumonia. This infant mouse model of pulmonary infection appears to be a useful system for the analysis of P. aeruginosa virulence factors involved in the pathogenesis of pneumonia. PMID- 7890386 TI - Phospholipid composition of Pneumocystis carinii carinii and effects of methylprednisolone immunosuppression on rat lung lipids. AB - The phospholipid class composition of Pneumocystis carinii carinii freshly isolated from infected lungs generally resembled that of the host lung, suggesting that the parasite scavenges lung alveolar lipids. However, subtle quantitative differences were demonstrated, indicating that the pathogen has the metabolic capacity to de novo synthesize, or at least tailor, its lipids. The concentration of phosphatidylcholine, the major lung surfactant lipid, in the organism was lower than that in lungs of normal and immunosuppressed uninfected rats, and the concentration of phosphatidylinositol was higher. Phosphonolipids were not detected in the organism by chemical analysis and nuclear magnetic resonance spectrometry. The immunosuppressive regimen alone caused increases in both surfactant protein A and the lipid content of the whole lung. The lungs of rats that were subjected to corticosteroid immunosuppression and had heavy parasite loads had dramatically elevated surfactant protein A levels, whereas the lipid contents of these lungs were not different from lipid contents in whole lungs of immunosuppressed uninfected rats. P. carinii was found to concentrate lipids, indicating that a large amount of the lipids in the whole infected rat lung was within the parasites residing in the organ. These observations have important implications relevant to the use of corticosteroid therapy for P. carinii pneumonitis. PMID- 7890387 TI - Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. AB - CAP18 (18-kDa cationic antimicrobial protein) is a protein originally identified and purified from rabbit leukocytes on the basis of its capacity to bind and inhibit various activities of lipopolysaccharide (LPS). Here we report the cloning of human CAP18 and characterize the anti-LPS activity of the C-terminal fragment. Oligonucleotide probes designed from the rabbit CAP18 cDNA were used to identify human CAP18 from a bone marrow cDNA library. The cDNA encodes a protein composed of a 30-amino-acid signal peptide, a 103-amino-acid N-terminal domain of unknown function, and a C-terminal domain of 37 amino acids homologous to the LPS binding antimicrobial domain of rabbit CAP18, designated CAP18(104-140). A human CAP18-specific antiserum was generated by using CAP18 expressed as a fusion protein with the maltose-binding protein. Western blots (immunoblots) with this antiserum showed specific expression of human CAP18 in granulocytes. Synthetic human CAP18(104-140) and a more active truncated fragment, CAP18(104-135), were shown to (i) bind to erythrocytes coated with diverse strains of LPS, (ii) inhibit LPS-induced release of nitric oxide from macrophages, (iii) inhibit LPS induced generation of tissue factor, and (iv) protect mice from LPS lethality. CAP18(104-140) may have therapeutic utility for conditions associated with elevated concentrations of LPS. PMID- 7890389 TI - Aggregative adherence of Klebsiella pneumoniae to human intestine-407 cells. AB - Aggregative adhesion of Klebsiella pneumoniae LM3 to Intestine-407 (Int-407) cells was studied. Adhesive capacities were affected by the bacterial growth phase (with a maximum of adherence obtained during the exponential phase), temperature, multiplicity of infection, and length of incubation with Int-407 cells. Adhesion occurred through a cytochalasin D-sensitive process and was greatly reduced after treatment of Int-407 with cycloheximide, indicating that aggregative adhesion requires active participation of Int-407 cells. Transmission electron microscopy revealed that adherent bacteria were surrounded by a capsule like material, apparently involved in both bacterium-Int-407 cell and bacterium bacterium adherence. Examination with a scanning electron microscope showed interactions of intestinal cell microvilli with bacteria and formation in 3 h of a fibrous network within and around the bacterial clusters. We speculate that aggregative adhesion of K. pneumoniae mediated by a capsule-like extracellular material might explain the persistence of these strains inside the host gastrointestinal tract. PMID- 7890388 TI - Breakdown of the round window membrane permeability barrier evoked by streptolysin O: possible etiologic role in development of sensorineural hearing loss in acute otitis media. AB - Sensorineural hearing loss is a common sequela of acute and chronic otitis media, and the round window membrane (RWM) is currently being considered as a major route for noxious agents to pass from the middle ear cavity to the cochlea. Streptococcus pneumoniae, a major causative agent of otitis media, and Streptococcus pyogenes A produce molecularly related toxins, pneumolysin and streptolysin O (SLO), that form large pores in target membranes. In this study, we analyzed the effects of SLO on the permeability of the RWM. Resected RWMs from a total of 104 guinea pigs were embedded between two chambers of an in vitro system. One chamber was designated as the tympanal (cis) compartment, and the other was designated as the inner ear (trans) compartment. The permeability of normal and SLO-damaged RWMs towards Na+, [14C]mannitol, and proteins was investigated. SLO evoked permeability defects dose dependently in the RWM with fluxes of both Na+ and [14C]mannitol being demonstrable over a time span of up to 8 h. Serum proteins and radioiodinated SLO were also shown to pass through the damage RWM. Scanning electron microscopy revealed the morphological correlates to these results. We propose that damage to the RWM by potent pore-forming cytolysins leads to leakage of ions from the perilymph. Ionic disequilibrium and passage of noxious macromolecules to the cochlea could contribute to disturbances of the inner ear function. PMID- 7890390 TI - Complement-independent binding of microorganisms to primate erythrocytes in vitro by cross-linked monoclonal antibodies via complement receptor 1. AB - Under certain circumstances, soluble antigens, particulate antigens, and/or microorganisms have been shown to bind to primate erythrocytes via complement receptor 1 (CR1) in the presence of specific antibodies and complement. This immune adherence reaction, specific for CR1, can lead to neutralization of antigens in the circulation and their subsequent clearance from the blood. The present experiments utilized cross-linked monoclonal antibody complexes (heteropolymers) with specificity for both CR1 and either 35S-labeled herpes simplex virus capsid or Haemophilus influenzae as prototype viral and bacterial particulate antigens, respectively. In each case, the respective specific heteropolymers facilitated binding of the target antigens (> or = 70 to 90%) in vitro to erythrocytes in the absence of complement. Several experimental protocols were employed to demonstrate that heteropolymers mediate specific, rapid (> or = 30 s), and quantitative binding of prototypical particulate pathogens to human and monkey erythrocytes but not to sheep erythrocytes, which lack CR1. These results extend the potential use of the erythrocyte-heteropolymer system to the neutralization and clearance of particulate viral and bacterial pathogens from the blood. PMID- 7890391 TI - Safety and immunogenicity of a live oral bivalent typhoid fever (Salmonella typhi Ty21a)-cholera (Vibrio cholerae CVD 103-HgR) vaccine in healthy adults. AB - The safety and immunogenicity of the live oral attenuated vaccine strains vibrio cholerae CVD 103-HgR and Salmonella typhi Ty21a were evaluated alone or in a combined bivalent formulation in four groups composed of 185 healthy European adults. All presentations were well tolerated. The serum anti-S. typhi lipopolysaccharide immunoglobulin G and immunoglobulin A antibody responses were comparable for all groups (66 to 72% seroconversion). The serum vibriocidal antibody seroconversion rate ranged from 78 to 92.5% (P > 0.05) among the groups. However, the peak and geometric mean vibriocidal antibody titers were significantly higher (P < 0.005) in the groups which received the bivalent formulation along with two doses of Ty21a than in the group which received CVD 103-HgR followed by two doses of killed Escherichia coli K-12 placebo. The ingestion of a placebo shortly after CVD 103-HgR may have suppressed the magnitude of the immune response. These findings demonstrate the feasibility of producing multivalent live oral attenuated vaccines. PMID- 7890392 TI - Pasteurella haemolytica serotype 2 contains the gene for a noncapsular serotype 1 specific antigen. AB - An ssa1-homologous genomic fragment cloned from Pasteurella haemolytica serotype 2 (ST2) enabled transformation of Escherichia coli DH5 alpha to a serotype 1 (ST1) phenotype through expression of the ST1-specific antigen (Ssa1). The Ssa1 protein expressed by ssa1-transformed E. coli was susceptible to heat and protease treatment and was distinct from P. haemolytica ST1-specific capsular polysaccharide. Electrophoretic analysis of in vitro-translated proteins, as well as the predicted amino acid sequence, demonstrated that Ssa1 proteins encoded from either ST1- or ST2-derived ssa1 genes were essentially identical. A comparison of the nucleotide sequences of ssa1 genes derived from P. haemolytica ST1 and ST2 revealed greater than 99% homology. Amino acid sequence homology of the predicted products of ST1- and ST2-derived ssa1 genes was greater than 98%. Northern (RNA) blot studies revealed that the presence of an increased level of ssa1 transcript in P. haemolytica ST1 grown as surface-adherent cultures on solid medium was correlated with a serologically detectable Ssa1 protein. Expression of the ssa1 transcript in ST1 was similarly upregulated by a high iron concentration in the growth medium. PMID- 7890393 TI - Oral immunization with the dodecapeptide repeat of the serine-rich Entamoeba histolytica protein (SREHP) fused to the cholera toxin B subunit induces a mucosal and systemic anti-SREHP antibody response. AB - The intestinal protozoan parasite Entamoeba histolytica causes amebic dysentery, a major cause of morbidity worldwide. The induction of a mucosal antibody response capable of blocking amebic adhesion to intestinal cells could represent an approach to preventing E. histolytica infection and disease. Here we describe the expression of a chimeric protein containing an immunogenic dodecapeptide derived from the serine-rich E. histolytica protein (SREHP), fused to the cholera toxin B subunit (CtxB). The CtxB-SREHP-12 chimeric protein was purified from Escherichia coli lysates and retained the critical GM1 ganglioside-binding activity of the CtxB moiety. Mice fed the CtxB-SREHP-12 fusion protein along with a subclinical dose of cholera toxin developed mucosal immunoglobulin A and immunoglobulin G and systemic antibody responses that recognized recombinant and native SREHP. Our study confirms the feasibility of inducing mucosal immune responses to immunogenic peptides by their genetic fusion to the CtxB subunit and identifies the CtxB-SREHP-12 chimeric protein as a candidate oral vaccine to prevent E. histolytica infection. PMID- 7890394 TI - Identification of an immunologically important hypervariable domain of major outer surface protein A of Borrelia burgdorferi. AB - The gene for the major outer surface protein A (OspA) from several clinically obtained strains of Borrelia burgdorferi, the cause of Lyme disease, has been cloned, sequenced, and expressed in Escherichia coli by using a T7-based expression system (J. J. Dunn, B. N. Lade, and A. G. Barbour, Protein Expr. Purif. 1:159-168, 1990). All of the OspAs have a single conserved tryptophan at residue 216 or, in some cases, 217; however, the region of the protein flanking the tryptophan is hypervariable, as determined by a moving-window population analysis of ospA from 15 European and North American isolates of B. burgdorferi. Epitope-mapping studies using chemically cleaved OspA and a TrpE-OspA fusion have indicated that this hypervariable region is important for immune recognition. Biophysical analysis, including fluorescence and circular dichroism spectroscopy, have indicated that the conserved tryptophan is buried in a hydrophobic environment. Polar amino acid side chains flanking the tryptophan are likely to be exposed to the hydrophilic solvent. The hypervariability of these solvent exposed amino acid residues may contribute to the antigenic variation in OspA. To test this, we have performed site-directed mutagenesis to replace some of the potentially exposed amino acid side chains in the B31 protein with the analogous residues of a Borrelia garinii strain, K48. The altered proteins were then analyzed by Western blot (immunoblot) with monoclonal antibodies which bind OspA on the surface of the intact B31 spirochete. Our results indicate that specific amino acid changes near the tryptophan can abolish the reactivity of OspA to these monoclonal antibodies, which is an important consideration in the design of vaccines based on recombinant OspA. PMID- 7890395 TI - Prolonged expression of lipopolysaccharide (LPS)-induced inflammatory genes in whole blood requires continual exposure to LPS. AB - Blood-borne lipopolysaccharide (LPS) is thought to be a major inducer of sepsis; however, it remains controversial whether an ongoing exposure to LPS is required to maintain the underlying systemic inflammatory response. To address this question, we have studied the expression of tumor necrosis factor alpha (TNF alpha), interleukin 1-beta (IL-1 beta), and the procoagulant protein tissue factor induced by LPS ex vivo in whole human blood. The addition of a 1-ng/ml bolus of LPS to blood rapidly induced mRNA expression of all three genes. The mRNA levels peaked after 1 to 2 h, depending on the gene, and then declined to baseline after approximately 5 h. The decline in mRNA expression was not caused by a loss of responsiveness of the blood cells to LPS but rather correlated with the neutralization of LPS inflammatory activity by plasma components. Furthermore, administering a 1-ng/ml dose of LPS in six hourly aliquots of 167 pg/ml greatly prolonged the expression of mRNAs and induced a much greater release of TNF-alpha and IL-1 beta protein than did a single bolus. Dosing by repeated additions was more effective than a single bolus in inducing secretion of TNF-alpha and IL-1 beta at LPS levels of < or = 10 ng/ml, which corresponded to the LPS neutralization capacity of plasma. Finally, both mRNA expression and protein secretion induced by repeated administration of LPS were rapidly reversed by the addition of the LPS-neutralizing protein, bactericidal/permeability increasing protein, even after several hours of stimulation. These results indicate that continuous or repeated exposure to LPS is required to maintain the expression of inflammatory genes and that the activated state is rapidly reversed with LPS neutralization. PMID- 7890396 TI - Protective immunity induced by Bacillus anthracis toxin-deficient strains. AB - The two toxins secreted by Bacillus anthracis are composed of binary combinations of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). Six mutant strains that are deficient in the production of one or two of these toxin components have been previously constructed and characterized (C. Pezard, E. Duflot, and M. Mock, J. Gen. Microbiol. 139:2459-2463, 1993). In this work, we examined the antibody response to the in vivo production of PA, LF, and EF in mice immunized with spores of strains producing these proteins. High titers of antibody to PA were observed after immunization with all strains producing PA, while titers of antibodies to EF and LF were weak in animals immunized with strains producing only EF or LF. In contrast, immunization with strains producing either PA and EF or PA and LF resulted in an increased antibody response to EF or LF, respectively. The differing levels of protection from a lethal anthrax challenge afforded to mice immunized with spores of the mutant strains not only confirm the role of PA as the major protective antigen in the humoral response but also indicate a significant contribution of LF and EF to immunoprotection. We observed, however, that PA-deficient strains were also able to provide some protection, thereby suggesting that immune mechanisms other than the humoral response may be involved in immunity to anthrax. Finally, a control strain lacking the toxin-encoding plasmid was unable to provide protection or elicit an antibody response against bacterial antigens, indicating a possible role for pXO1 in the survival of B. anthracis in a host. PMID- 7890397 TI - Expression of surface hydrophobic proteins by Candida albicans in vivo. AB - Candida albicans modulates cell surface hydrophobicity during growth and morphogenesis in vitro. To determine if surface hydrophobicity is expressed during pathogenesis, we generated a polyclonal antiserum against yeast hydrophobic proteins. The antiserum was then used for indirect immunofluorescence analysis of tissues from mice colonized and chronically infected with C. albicans. Results demonstrated that yeast hydrophobic proteins are exposed on fungal cells present in host tissues. The polyclonal antiserum distinguished between hydrophobic and hydrophilic cell surfaces in vitro and gave similar staining patterns and intensities for C. albicans cells in vivo. Of the yeast forms present within tissue lesions, approximately half exhibited moderate to intense immunofluorescence with the antiserum. Immunoblot analysis indicated that antigens recognized by the antiserum are predominantly low-molecular-mass hydrophobic proteins that are expressed by different C. albicans isolates and are expressed regardless of growth temperature. Taken together, the immunofluorescence and immunoblot analyses of antigens indicate that C. albicans displays surface hydrophobic proteins during pathogenesis and these proteins are available for hydrophobic interactions with host tissues. The effect of hydrophobic protein exposure on the virulence of C. albicans is discussed. PMID- 7890398 TI - Capsular polysaccharide types 5 and 8 of Staphylococcus aureus bind specifically to human epithelial (KB) cells, endothelial cells, and monocytes and induce release of cytokines. AB - In order to examine the possible implication of capsular polysaccharide (CP) types 5 and 8 (CP5 and CP8) from Staphylococcus aureus in the pathological mechanism associated with staphylococcal infections, we tested the immunomodulatory effects of CP5 and CP8 on human epithelial KB cells, endothelial cells, and monocytes. Using biotinylated CP5 and CP8, we provide evidence that both CPs bind to KB cells, endothelial cells, and monocytes in a dose- and calcium-dependent manner through specific interactions. These results were confirmed by competition experiments using soluble cell extracts. Furthermore, we show that CPs bind to identical cell membrane receptors on all three types of human cells and that human normal serum contains a factor(s) which inhibits the binding of both CPs to human KB cells, endothelial cells, and monocytes. The ability of CP5 and CP8 to stimulate the production of cytokines by the human cells was then examined. CP5 and CP8 trigger KB cells to produce interleukin-8 (IL-8); endothelial cells to produce IL-8 and IL-6; and monocytes to produce IL 8, IL-6, IL-1 beta, and tumor necrosis factor alpha. The release of cytokines by all three types of cells is time dependent and dose dependent, and the tumor necrosis factor alpha production by monocytes is not affected by the addition of polymyxin B. We further confirm that human normal serum inhibits the immunomodulatory effects of both polysaccharides on each kind of cell. These results confirm that S. aureus CPs act as bacterial adhesins having immunomodulatory effects for human cells. PMID- 7890399 TI - Endogenous interleukin-12 is involved in resistance to Brucella abortus infection. AB - Protective immunity against Brucella abortus is mediated by acquired cellular resistance, with gamma interferon (IFN-gamma)-producing T cells playing a key role. Interleukin-12 (IL-12) is a cytokine that has a profound effect on the induction of IFN-gamma-producing Th1 and NK cells. Here we report that depletion of endogenous IL-12 before infection of mice significantly exacerbated brucella infection. IL-12-depleted mice also had reduced splenomegaly resulting from infection and showed a decrease in percentage and absolute numbers of macrophages compared with those in control infected mice. Furthermore, spleen cells from IL 12-depleted mice had a reduced ability to produce nitrite, a product of activated macrophages. This could be the result of the low production of IFN-gamma by splenic T cells observed in the IL-12-depleted mice. The mechanism whereby IL-12 controls antibacterial resistance is discussed. PMID- 7890400 TI - Deviation of immune response to Chlamydia psittaci outer membrane protein in lipopolysaccharide-hyporesponsive mice. AB - The outcome of infection is determined by both the quantity and the quality of an induced immune response. In particular, it has been demonstrated for selected pathogens that induction of TH1 or TH2 type helper T-cell subsets determines whether an immune response gives rise to protective immunity or disease associated immunopathology. The nature of the antigen and the type of antigen presenting cells recruited in the induction of a response are critical factors that influence the quality of the immune response. Of particular interest in this respect is the immune response to bacterial particles and the impact of cell wall associated lipopolysaccharide (LPS) on that response. Nonspecific activation of macrophages and B lymphocytes by LPS could skew the phenotype of activated antigen-presenting cells and selectively alter the immunoglobulin isotypes and helper T-cell subsets that are induced following infection. In an initial attempt to detect immune deviation associated with LPS stimulation, we have compared the immunoglobulin isotypes of antibodies specific for the cysteine-rich outer membrane protein Omp2 induced in normal and LPS-hyporesponsive mice following immunization with Chlamydia psittaci strain guinea pig inclusion conjunctivitis whole elementary bodies. We report that there is a dramatic shift of Omp2 specific antibody from predominantly immunoglobulin G2a (IgG2a) isotype in LPS hyporesponsive mice to high levels of IgG1 isotype in LPS-responder strains. The dependence of the IgG1 isotype shift on the LPS responder status is linked to the structure of the antigen and its natural processing pathway since LPS hyporesponsive mice are not, in general, deficient in IgG1 antibody production. In particular, the antibody response to purified recombinant Omp2 is predominantly of the IgG1 isotype even in LPS-hyporesponsive mice. PMID- 7890401 TI - Urease-specific monoclonal antibodies prevent Helicobacter felis infection in mice. AB - Experiments were performed to determine the antigenic specificity of a monoclonal antibody (immunoglobulin A [IgA] 71) previously demonstrated to neutralize the ability of Helicobacter felis to colonize mice. Immunoprecipitation of radiolabeled H. felis outer membrane proteins with IgA 71 revealed specificity for a 62-kDa protein. Another of our monoclonal antibodies, IgG 40, precipitated a protein of similar molecular weight. IgA 71 but not IgG 40 also precipitated purified recombinant H. pylori urease. The antigenic specificity of both antibodies was confirmed to be urease by the ability of each to select Escherichia coli clones expressing the H. felis urease genes. The two antibodies were shown to bind nonoverlapping epitopes in a competition enzyme-linked immunosorbent assay. Both IgA 71 and IgG 40 could effectively neutralize H. felis infectivity by incubating the bacteria with the antibodies prior to oral administration to naive mice. The mechanism of protection does not appear to be inhibition of urease activity, as IgA 71 does not inhibit the conversion of urea to ammonia by H. pylori urease in vitro. These results support a protective role for the secretory humoral immune response in Helicobacter immunity and provide further evidence that the urease enzyme can serve as a protective antigen. PMID- 7890403 TI - Protein synthesis in Brucella abortus induced during macrophage infection. AB - Brucella abortus is a facultative, intracellular, pathogenic bacterium that replicates within macrophages and resists macrophage microbicidal mechanisms. To study gene expression and to elucidate the defense mechanisms used by B. abortus to resist destruction within macrophages, protein synthesis by B. abortus was examined by pulse-labeling techniques during intracellular growth within J774A.1, a macrophage-like cell line. Prominent changes observed include increased synthesis of Brucella proteins with estimated molecular masses of 62, 28, 24, and 17 kDa. The 62-kDa protein was identified by immunoprecipitation analysis as Hsp62, a GroEL homolog. A protein of 60 kDa was expressed during acid shock and may represent a modified form of Hsp62. The 28- and 17-kDa proteins have not been observed under any in vitro stress condition and presumably represent macrophage specific induction. The 24-kDa protein comigrates with an unidentified protein induced by acid shock, designated Asp24. Expression of Asp24 is optimal at pH values below 4.0 and within the first 3 h following a shift from pH 7.3 to 3.8. This corresponds directly with a period of optimal bacterial survival at a reduced pH and suggests an active role for this protein in resistance to such environments. The identification of these gene products and the mechanisms controlling their expression is an important step in understanding the resistance of Brucella spp. to intracellular destruction within macrophages. PMID- 7890402 TI - Borrelia burgdorferi-specific T lymphocytes induce severe destructive Lyme arthritis. AB - This is the first documentation that Borrelia burgdorferi-specific T lymphocytes are involved in the pathogenesis of Lyme arthritis. We present direct evidence that T lymphocytes obtained from inbred LSH hamsters vaccinated with a whole-cell preparation of Formalin-inactivated B. burgdorferi sensu stricto isolate C-1-11 in adjuvant conferred on naive recipient hamsters the ability to develop severe destructive arthritis when challenged with B. burgdorferi sensu stricto isolates C-1-11 and 297. By contrast, recipients infused with normal T lymphocytes and challenged with B. burgdorferi sensu stricto isolates C-1-11 and 297 failed to develop severe destructive arthritis. The T lymphocytes transferred were obtained from the lymph nodes of vaccinated and nonvaccinated hamsters by depleting B lymphocytes by using monoclonal antibody 14-4-4s (< 1% B lymphocytes by flow cytometric analysis). The enriched T lymphocytes showed enhanced proliferation to stimulation with concanavalin A and failed to respond to lipopolysaccharide. Moreover, only the enriched T lymphocytes from vaccinated hamsters proliferated on exposure to a whole-cell preparation of B. burgdorferi sensu stricto isolate C 1-11 in the presence of mitomycin-treated syngeneic antigen-presenting cells. These results demonstrate that B. burgdorferi-specific T lymphocytes primed by vaccination with a whole-cell preparation of inactivated B. burgdorferi sensu stricto isolate C-1-11 in adjuvant are involved in the development of severe destructive arthritis. Additional experiments are needed to define the precise mechanism(s) responsible for the development of Lyme arthritis. PMID- 7890404 TI - Involvement of Ras-related Rho proteins in the mechanisms of action of Clostridium difficile toxin A and toxin B. AB - Toxins A and B of Clostridium difficile are responsible for pseudomembranous colitis, a disease that afflicts a substantial number of hospitalized patients treated with antibiotics. A major effect of these proteins is the disruption of the actin cytoskeleton. Recently, I. Just, G. Fritz, K. Aktories, M. Giry, M. R. Popoff, P. Boquet, S. Hegenbarth, and C. von Eichel-Streiber (J. Biol. Chem. 269:10706-10712, 1994) implicated Rho proteins as cellular targets of C. difficile toxin B, since pretreatment of cells or purified Rho with toxin prevented subsequent ADP-ribosylation of Rho by exoenzyme C3. Moreover, they showed that overexpression of Rho proteins in cells suppressed cell rounding normally associated with exposure of cells to C. difficile toxin B. Here we expand these findings by showing directly that Rho proteins are covalently modified by both C. difficile toxins A and B. In addition, we demonstrate that the stability of toxin-modified Rho in NIH 3T3 cells is dramatically reduced. Finally, we show that C. difficile toxins A and B do not have similar effects on the closely related Rac and CDC42 GTP-binding proteins. PMID- 7890405 TI - Molecular mechanisms of isoniazid resistance in Mycobacterium tuberculosis and Mycobacterium bovis. AB - Genetic and biochemical studies have suggested a link between reduced catalase activity and resistance to isoniazid in Mycobacterium tuberculosis. In this study, we examined the molecular mechanisms of resistance to isoniazid with six in vitro mutants of the M. tuberculosis complex (Mycobacterium bovis and M. tuberculosis). Five of six mutants resistant to isoniazid were negative by catalase assays. Immunoblot analyses using a polyclonal antibody against the katG gene product (catalase-peroxidase) demonstrated that the enzyme is not produced in four of these isoniazid-resistant strains. A complete deletion of the katG gene was detected in only one of these isoniazid-resistant M. tuberculosis complex strains by Southern blot analyses. In two other resistant strains, partial deletions of the katG gene were identified. A point mutation which resulted in the insertion of a termination codon in the katG coding sequence caused a catalase-negative phenotype in a fourth strain. Of the two resistant strains which produce the enzyme, one was shown to be negative by a catalase assay. Single-stranded conformational polymorphism and DNA sequence analyses identified a mutation in the katG gene of this strain which may contribute to reduced enzymatic activity and subsequent isoniazid resistance. These data demonstrate that genetic alterations to the katG gene other than complete deletions are prevalent and may contribute significantly to the number of cases of isoniazid-resistant tuberculosis. PMID- 7890407 TI - Cloning and sequence analysis of a protective M-like protein gene from Streptococcus equi subsp. zooepidemicus. AB - Streptococcus equi subsp. zooepidemicus, a Lancefield group C streptococcus, is a frequently isolated opportunist pathogen from a variety of animal hosts, including the horse. Previous studies have indicated that equine strains carry antigens with characteristics of the antiphagocytic M proteins on the Lancefield groups A and G streptococci. We have cloned a protective M-like protein gene (SzPW60) of an equine strain of S. equi subsp. zooepidemicus W60 and determined its sequence. This gene encodes a protein with a molecular weight of 40,123 which protects mice against subsp. zooepidemicus but not subsp. equi, stimulates antibodies which opsonize subsp. zooepidemicus but not equi, and reacts with antiserum to the protein of the parent strain. The predicted amino acid structure shows significant homology with the carboxy termini of groups A and G M proteins but no other homology. The M-like protein, although showing an extensive region of alpha helix, lacks the A, B, and C repeats found in group A M proteins and has a shorter signal sequence. A proline-rich region upstream from the LPSTGE motif contains 20 repeats of the tetrapeptide PEPK. The presence of this repeat region may account for the slow migration of the M-like protein in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. PMID- 7890406 TI - Gonococcal opacity: lectin-like interactions between Opa proteins and lipooligosaccharide. AB - Previous evidence from our laboratory suggested that the tight intercellular adhesions between the outer membranes of gonococci displaying the opacity colony phenotype occurred because Opa proteins expressed on one gonococcus adhered to the lipooligosaccharide (LOS) of the opposing bacterium (M.S. Blake, p. 51-66, in G. G. Jackson and H. Thomas, ed., The Pathogenesis of Bacterial Infections, 1985, and M. S. Blake and E. C. Gotschlich, p. 377-400, in M. Inouye, ed., Bacterial Outer Membranes as Model Systems, 1986). A noncompetitive inhibition assay used previously to determine the carbohydrate structures recognized by the major hepatic asialoglycoprotein receptor was modified to determine the gonococcal LOS structures that bind Opa proteins (R. T. Lee, Targeted Diagn. Ther. Ser. 4:65-84, 1991). The LOS carbohydrates used in these assays were LOS structures purified from pyocin LOS mutants of Neisseria gonorrhoeae 1291 described by K. C. Dudas and M. A. Apicella (Infect. Immun. 56:499-504, 1988) and further characterized by C. M. John et al. (J. Biol. Chem. 266:19303-19311, 1991). Purified gonococcal Opa proteins were incubated with each of the parent and mutant LOS, and the amount of binding of Opa proteins was measured by a direct enzyme-linked immunosorbent assay using the Opa-specific monoclonal antibody 4B12. The affinities of the Opa proteins for each of the LOS were determined indirectly by measuring the concentrations of Opa proteins that noncompetitively inhibited 50% of the binding of LOS-specific monoclonal antibodies. This concentration is inversely proportional to the affinity of the inhibitor (R. T. Lee, Targeted Diagn. Ther. Ser. 4:65-84, 1991). Our data suggest that the gonococcal Opa proteins tested had the highest affinity for the Gal beta 1-4GlcNAc residue present on the gonococcal lactoneoseries LOS. This affinity was comparable to that reported for the binding of the major hepatic asialoglycoprotein receptor to glycoconjugates containing terminal galactose and N-acetylgalactosamine (R. T. Lee, Targeted Diagn. Ther. Ser. 4:65-84, 1991). After sialylation of the lactoneoseries LOS, presumably on the terminal galactose residue, the interaction with the Opa proteins was ablated. Therefore, the gonococcal Opa-LOS and mammalian epithelial cell asialoglycoprotein receptor-carbohydrate interactions have quite similar specificities. PMID- 7890408 TI - Expression of endotoxic activities by synthetic monosaccharide lipid A analogs with alkyl-branched acyl substituents. AB - Synthetic monosaccharide lipid A analogs with alkyl-branched acyl substituents instead of the usual ester-branched acyl substituents were investigated for their biological activities. The activities were compared with those of a representative synthetic monosaccharide lipid A analog with an ester branch (GLA 60) and synthetic complete lipid A (506) to estimate the role of the attaching mode of the branched side chains for expression of endotoxic activities. Among the analogs with alkyl branches, GLA-146 and GLA-147, which have C12 and C14 alkyl side chains, respectively, showed strong endotoxic activities. These analogs exhibited comparable or stronger activities than those of GLA-60 in murine macrophage activation activities to induce mediators such as tumor necrosis factors, interleukin 6, and nitric oxide and in mitogenic activity towards murine spleen cells; however, these activities were weaker than the respective activities of 506. With respect to lethal toxicity to galactosamine sensitized mice, the analogs showed stronger activity than that of GLA-60 and activity closer to that of 506. With respect to adjuvant activity, no significant activity was observed in the analogs, while the activities of GLA-60 and 506 were strong. When lipopolysaccharide-resistant C3H/HeJ mice were used, the activities described above were not observed either for the analogs under investigation nor for GLA-60 and 506. These findings indicate that the ester type of branch in lipid A and its analogs does not play an indispensable role in the expression of various endotoxic activities. However, it may play some role in the expression of adjuvant activity and in lowering the level of toxicity. PMID- 7890409 TI - Comparison of the mechanisms of action of cholera toxin and the heat-stable enterotoxins of Escherichia coli. AB - The mechanisms which enable cholera toxin (CT) and the Escherichia coli heat stable enterotoxins (STa and STb) to stimulate intestinal secretion of water and electrolytes are only partially understood. CT evokes the synthesis of 3',5' cyclic AMP (cAMP), and STa is known to elevate intestinal levels of 3',5'-cyclic GMP (cGMP). Neither of these recognized second messengers appears to mediate E. coli STb responses. We compared the secretory effects of CT, STa, and STb using the pig intestinal loop model and also measured the effects of toxin challenge on the synthesis of cAMP, cGMP, and prostaglandins (e.g., prostaglandin E2 [PGE2]), as well as on the release of 5-hydroxytryptamine (5-HT) from intestinal enterochromaffin cells. All three enterotoxins elicited fluid accumulation within a 2-h observation period. A combination of maximal doses of STa with STb yielded additive effects on fluid accumulation, which suggested different mechanisms of action for these toxins. Similarly, challenge of pig intestinal loops with a combination of CT and STb resulted in additive effects on fluid accumulation and luminal release of 5-HT. Unlike its effect on intestinal tissues from other animals, CT did not appear to elicit a dose-dependent cAMP response measurable in mucosal extracts from pig small intestine. In contrast, luminal fluid from CT challenged pig intestinal loops contained dose-related amounts of cAMP and PGE2 that had been secreted from the mucosa. cAMP responses to STa or STb could not be demonstrated in either mucosal tissue or luminal fluid. In contrast, cGMP levels were increased in the intestinal fluid of loops challenged with STa but not in those challenged with STb. While the mechanisms of action of CT and STa are thought to involve impulse transmission via the enteric nervous system, we demonstrated significant stimulation of PGE2 synthesis and 5-HT release for CT and STb but very little for STa. We conclude from these data that the mechanisms of action of STa, STb, and CT are distinct, although the mode of action of STb may have some similarity to that of CT. Since STb stimulated the release of both PGE2 and 5-HT from the intestinal mucosa, the data suggested the potential for an effect of STb on the enteric nervous system. PMID- 7890410 TI - Association with MDCK epithelial cells by Salmonella typhimurium is reduced during utilization of carbohydrates. AB - Association of Salmonella typhimurium with MDCK epithelial cells in monolayers, represented primarily by intracellular bacteria after 30 min of contact, with centrifugation followed by vigorous washing, was measured during aerobic and anaerobic growth of the bacteria in brain heart infusion broth. Cell association was greatest during a short period in the late log phase of growth under aerobic conditions. At this time, the pH of the growth medium was changing from acid to alkaline and glucose (0.2% initially) was exhausted. Addition of excess glucose (0.5%) to brain heart infusion broth, which was not exhausted before the bacteria entered the stationary phase of growth, in which cell association dropped sharply, resulted in repression of cell association by the bacteria. The repressive effect of glucose on cell association could not be reversed by exogenous cyclic AMP in the bacterial growth medium. Under anaerobic conditions, the effect of glucose on cell association by the bacteria was not as great and the glucose was not exhausted before the bacteria entered the stationary phase. When S. typhimurium was grown in a rich but carbohydrate-free medium, cell association by the bacteria increased earlier in the growth cycle under both aerobic and anaerobic conditions. The addition of glucose and certain other utilizable carbohydrates to this medium caused a repression of cell association by S. typhimurium that was greater under aerobic growth conditions. These results show that cell association by S. typhimurium, which is accompanied by rapid internalization (cell invasion), is the same under aerobic and anaerobic conditions if the bacteria are grown to the log phase in a carbohydrate-free medium. This suggests that prior reports of greater cell invasion by S. typhimurium during anaerobic growth may have arisen from the use of media containing carbohydrates which were found to be more repressive during aerobic growth of the bacteria. PMID- 7890411 TI - Impaired responsiveness to gamma interferon of macrophages infected with lymphocytic choriomeningitis virus clone 13: susceptibility to histoplasmosis. AB - Lymphocytic choriomeningitis virus clone 13 (LCMV clone 13), a variant isolated from the spleens of neonatally infected mice, causes persistent infections in mice infected as adults. Such persistently infected mice succumb to a normally sublethal dose of Histoplasma capsulatum, and their macrophages contain overwhelming numbers of yeast cells of the fungus. Both LCMV clone 13 and H. capsulatum yeast cells target and replicate in macrophages of the host. We sought to study the effects of LCMV clone 13 on the ability of macrophages to control growth of H. capsulatum in vitro. We show that the growth of H. capsulatum within macrophages was not directly affected by the presence of LCMV clone 13. However, macrophages containing LCMV clone 13 did not respond fully to gamma interferon (IFN-gamma) stimulation. Such unresponsiveness resulted in proliferation of the fungus within macrophages cultured in the presence of IFN-gamma. The addition of anti-IFN-alpha/beta antibodies to LCMV clone 13-infected macrophage cultures restored macrophage responsiveness to IFN-gamma. These results indicate that production of IFN-alpha/beta by LCMV clone 13-infected macrophages antagonizes their responsiveness to IFN-gamma. Such antagonism may be one of the mechanisms by means of which certain viruses cause immune suppression and susceptibility to opportunistic infections. PMID- 7890412 TI - Independent down-regulation of central and peripheral tumor necrosis factor production as a result of lipopolysaccharide tolerance in mice. AB - Lipopolysaccharide (LPS) induces a variety of central and peripheral effects that are largely mediated by cytokines, including tumor necrosis factor (TNF). Peripheral (intravenous [i.v.]) administration of LPS (2.5 micrograms per mouse) induced TNF levels in the serum and spleen but not in the brain, while central (intracerebroventricular [i.c.v.]) administration of LPS induced TNF production both in the brain and in the periphery. Mice challenged with LPS after LPS pretreatment (35 micrograms per mouse, intraperitoneally, as a single dose on day -3 or as a 4-day treatment on days -5 to -2) were unresponsive in terms of induction of serum TNF. When peripherally LPS-tolerant mice (where LPS pretreatment was given intraperitoneally) were challenged with an i.c.v. dose of LPS, brain (but not serum) TNF was still produced, meaning that the LPS-tolerant state was confined to the periphery. However, if LPS pretreatment was given i.c.v. (35 micrograms, as a single dose), the brain, like the periphery, became LPS tolerant in terms of TNF production. We investigated how tolerance to LPS affected two of its actions, decrease in food intake and induction of serum corticosterone (CS). After an i.v. challenge in peripherally LPS-tolerant mice, no decrease in food intake was observed, but this response was still elicited by an i.c.v. challenge. LPS tolerance reduced the CS response to i.v. and i.c.v. challenge. These results suggest that LPS-induced decrease in food intake might be a fully central effect, while the increase of serum CS might be due to both central and peripheral actions. PMID- 7890413 TI - Growth of Francisella tularensis LVS in macrophages: the acidic intracellular compartment provides essential iron required for growth. AB - Murine macrophages supported exponential intracellular growth of Francisella tularensis LVS in vitro with a doubling time of 4 to 6 h. LVS was internalized and remained in a vacuolar compartment throughout its growth cycle. The importance of endosome acidification to intracellular growth of this bacterium was assessed by treatment of LVS-infected macrophages with several different lysosomotropic agents (chloroquine, NH4Cl, and ouabain). Regardless of the agent used or its mechanism of action, macrophages treated with agents that blocked endosome acidification no longer supported replication of LVS. Over several experiments for each lysosomotropic agent, the number of CFU of LVS recovered from treated macrophage cultures was equivalent to the input inoculum (approximately 10(4) CFU) at 72 h. In contrast, over 10(8) CFU was consistently recovered from untreated cultures. Pretreatment of macrophages with these endosome acidification inhibitors did not alter their ingestion of bacteria. Further, the effects of the inhibitors were completely reversible: inhibitor pretreated LVS-infected macrophages washed free of the agent and cultured in medium fully supported LVS growth over 72 h. Endosome acidification is an important cellular event essential for release of iron from transferrin. The growth-inhibitory effects of both chloroquine and NH4Cl were completely reversed by addition of ferric PPi, a transferrin-independent iron source, at a neutral pH but not by addition of excess holotransferrin. Thus, intracellular localization in an acidic vesicle which facilitates the availability of iron essential for Francisella growth is a survival tactic of this bacterium, and iron depletion is one mechanism that macrophages use to inhibit its growth. PMID- 7890414 TI - Analysis of Neisseria meningitidis class 3 outer membrane protein gene variable regions and type identification using genetic techniques. AB - The class 3 porin proteins of Neisseria meningitidis stimulate bactericidal antibodies and express serotype-specific antigenic epitopes. Sequence analysis of porB genes for the class 3 proteins revealed regions of variability that map to surface-exposed loops. To evaluate the relationship between serotype and variable region (VR) genotype, sequences from the 11 class 3-expressing serotype strains and 3 additional serotype 4 strains were analyzed by molecular techniques. Multiple-sequence alignment revealed a limited number of unique sequences at each of four VRs (VR1 to VR4), ranging from four unique sequences at VR1 to seven sequence patterns at VR2 and VR4. Serotype-specific VR sequences were found in each of the four VRs, suggesting that each VR has immunologic importance. Five serotypes had at least one VR sequence that was unique. Three serotypes which had sequences in common with other serotypes at each VR were distinguished by examining multiple VRs. Serotype 3 was identical to serotype 19 at each VR, and serotype 8 was identical to serotype 18 at each VR. Serotypes 4 and 21 were identical at VR1 and significantly different at VR3 and VR4. A subpopulation of serotype 4 strains with a unique VR2 sequence was identified. The serotypes which were grouped with closely related or identical sequences at one VR were grouped with different serotypes at other VRs consistent with the pattern of genetic mosaicism described for the porA (class 1 protein) gene. Hybridization assays demonstrated the ability to identify VR genotypes and distinguish serotypes using biotin-labelled oligonucleotide probes. This information may be useful in strain selection for vaccine development, in epidemiologic studies to determine the prevalence of the individual VR genotype (especially among nonserotypeable strains) and, combined with PCR, in the identification of culture-negative suspected meningococcal cases. PMID- 7890415 TI - Human T-cell responses to secreted antigen fractions of Mycobacterium tuberculosis. AB - The T-cell response of human donors to secreted antigen fractions of Mycobacterium tuberculosis was investigated. The donors were divided into five groups: active pulmonary tuberculosis (TB) patients with minimal and with advanced disease, Mycobacterium bovis BCG-vaccinated donors with and without contact with TB patients, and nonvaccinated individuals. We found that patients with active minimal TB responded powerfully to secreted antigens contained in a short-term culture filtrate. The response to secreted antigens was mediated by CD4+ Th-1-like lymphocytes, and the gamma interferon release by these cells was markedly higher in patients with active minimal TB than in healthy BCG-vaccinated donors. Patients with active advanced disease exhibited depressed responses to all preparations tested. The specificity of the response to secreted antigens was investigated by stimulating lymphocytes with narrow-molecular-mass fractions of short-term culture filtrate obtained by the multielution technique. Considerable heterogeneity was found within the donor groups. Patients with active minimal TB recognized multiple secreted targets, but interestingly, six of eight patients demonstrated a predominant recognition of a low-mass (< 10-kDa) protein fraction which induced high levels of gamma interferon release in vitro. Only a few of 12 previously characterized secreted antigens were recognized by T cells isolated from TB patients, suggesting the existence of a number of as yet undefined antigenic targets among secreted antigens. PMID- 7890417 TI - Dermal inflammation elicited by synthetic analogs of Treponema pallidum and Borrelia burgdorferi lipoproteins. AB - The membrane lipoproteins of Treponema pallidum and Borrelia burgdorferi have potent immunostimulatory properties in vitro, implicating them as major inflammatory mediators in syphilis and Lyme disease. Recently, we reported that synthetic lipohexapeptide analogs (lipopeptides) of the lipoproteins could be used as surrogates for native spirochetal lipoproteins in immune cell activation studies in vitro. The present study was designed to evaluate the inflammatory properties of the lipopeptides in vivo and to correlate the cellular responses to these synthetic analogs with the histopathology of syphilis and Lyme disease. Lipopeptides corresponding to the 47-kDa major membrane lipoprotein of T. pallidum and the outer surface protein A of B. burgdorferi injected intradermally induced dose-dependent dermal inflammation in mice; the initial predominantly neutrophilic (mice) or heterophilic (rabbits) cellular infiltrates were followed by infiltrates consisting predominantly of mononuclear cells. The intradermal response of rabbits to the 47-kDa lipopeptide was strikingly similar to that observed for animals infected intradermally with T. pallidum. In all cases, lipopolysaccharide was substantially more potent as an inflammatory mediator than the spirochetal lipopeptides. In contrast to the lipopeptides, nonacylated hexapeptides elicited minimal or no dermal lesions in mice or rabbits, underscoring the importance of acyl modification to the inflammatory properties of the lipopeptides. This study provides the first in vivo evidence that the spirochetal lipoproteins/lipopeptides contribute to the immunopathogenesis of syphilis and Lyme disease. PMID- 7890416 TI - Neisseria gonorrhoeae utilizes and enhances the biosynthesis of the asialoglycoprotein receptor expressed on the surface of the hepatic HepG2 cell line. AB - One of the lipooligosaccharide (LOS) structures of Neisseria gonorrhoeae contains a terminal Gal(beta 1-4)GlcNAc residue which is a good candidate to serve as a ligand for human asialoglycoprotein receptors (ASGP-R). These receptors have been shown to be present on macrophages, sperm cells, and hepatocytes. The human tissue culture cell line used most often to study this receptor, HepG2, was used in our investigations only as a model. We also chose N. gonorrhoeae 1291 for these studies because, unlike many other gonococcal strains, this strain expresses one main species of LOS. The LOS structure expressed by this strain has also been fully characterized. Using well-established assays for the utilization of the ASGP-R, we found that incubation of HepG2 cells with gonococci expressing the terminal Gal(beta 1-4)GlcNAc asialo-LOS carbohydrate structure competitively inhibited the ASGP-R from binding to one of its well-known ligands, asialo-alpha acid-1-glycoprotein. The inhibition was specific to the ASGP-R, since binding of two other ligands to their specific receptors in the same model cell system was not affected. Immunoblot analysis for the ASGP-R suggested that gonococci seemed to stimulate the HepG2 cells to increase the expression of the major (46-kDa) receptor species. This observation was confirmed both by functional analysis, which showed that the concentration of total receptor molecules, as well as surface receptors, was about 60% higher after incubation with gonococci than in control cells and by Northern (RNA) blot analysis using a cDNA probe of the major human H1 subunit. Poly(A) RNA purified from control and HepG2 cells exposed to gonococci indicated the presence of increased amounts of mRNA coding for the ASGP R after incubation with gonococci. This result supports the idea that the molecular mechanism controlling the receptor level after gonococcal exposure is under transcriptional regulation. PMID- 7890418 TI - Serum antibodies to outer membrane proteins (OMPs) of Moraxella (Branhamella) catarrhalis in patients with bronchiectasis: identification of OMP B1 as an important antigen. AB - Moraxella (Branhamella) catarrhalis is a common cause of lower respiratory tract infections in adults and of otitis media in children. Little is known about the human immune response to this bacterium. In this study, immunoblot assays were performed to detect serum immunoglobulin G antibodies directed at purified outer membrane of M. catarrhalis. Twelve serum samples, two each from six patients with bronchiectasis who were persistently colonized with this organism, were tested with their homologous M. catarrhalis sputum isolates. In all the sera, the most prominent and consistent antibody response was to a minor 84-kDa outer membrane protein, OMP B1. Immunoblot adsorption assays show that these antibodies recognize surface exposed epitopes on OMP B1. Further analysis of human serum antibodies eluted from the surface of intact bacterial cells shows that these surface-exposed epitopes on OMP B1 are heterogeneous among strains of M. catarrhalis. OMP B1 is therefore an important OMP antigen on the surface of M. catarrhalis for the human immune response to infection by this bacterium. PMID- 7890419 TI - Virulence of a Porphyromonas gingivalis W83 mutant defective in the prtH gene. AB - In a previous study we cloned and determined the nucleotide sequence of the prtH gene from Porphyromonas gingivalis W83. This gene specifies a 97-kDa protease which is normally found in the membrane vesicles produced by P. gingivalis and which cleaves the C3 complement protein under defined conditions. We developed a novel ermF-ermAM antibiotic resistance gene cassette, which was used with the cloned prtH gene to prepare an insertionally inactivated allele of this gene. This genetic construct was introduced by electroporation into P. gingivalis W83 in order to create a protease-deficient mutant by recombinational allelic exchange. The mutant strain, designated V2296, was compared with the parent strain W83 for proteolytic activity and virulence. Extracellular protein preparations from V2296 showed decreased proteolytic activity compared with preparations from W83. Casein substrate zymography revealed that the 97-kDa proteolytic component as well as a 45-kDa protease was missing in the mutant. In in vivo experiments using a mouse model, V2296 was dramatically reduced in virulence compared with the wild-type W83 strain. A molecular survey of several clinical isolates of P. gingivalis using the prtH gene as a probe suggested that prtH gene sequences were conserved and that they may have been present in multiple copies. Two of 10 isolates did not hybridize with the prtH gene probe. These strains, like the V2296 mutant, also displayed decreased virulence in the mouse model. Taken together, these results suggest an important role for P. gingivalis proteases in soft tissue infections and specifically indicate that the prtH gene product is a virulence factor. PMID- 7890420 TI - Lipopolysaccharide-inducible and salicylate-sensitive nuclear factor(s) on human tumor necrosis factor alpha promoter. AB - Lipopolysaccharide (LPS) is one of the most potent trigger substances for monocytes and macrophages causing secretion of tumor necrosis factor alpha (TNF alpha) and other inflammatory mediators. The nature of the nuclear factors involved in human TNF-alpha gene regulation is still unknown. Nuclear factor kappa B (NF-kappa B) proteins have been suggested to play an important role in gene transcription of inflammatory mediators when monocytes are stimulated with LPS. However, it remains unclear whether these nuclear factors are the only ones involved in human TNF-alpha gene regulation. In this report, to further the identification of nuclear factor(s) involved in TNF-alpha gene regulation, human monocytic THP-1 cells were transfected with a series of truncated versions of human TNF-alpha promoter. A 98-bp region located from nucleotides -584 to -487 demonstrated strong promoter activity. Electrophoretic mobility shift assays demonstrated that a 64-bp fragment located within the 98-bp region and lacking any potential NF-kappa B-binding sites avidly bound LPS-challenged THP-1 nuclear protein. Although this binding was inhibited in salicylate-treated cells, as was binding of NF-kappa B, the pattern of binding was found to differ from that noted for NF-kappa B. Analysis of this 64-bp fragment disclosed the absence of an NF kappa B consensus sequence, suggesting a novel nuclear DNA-binding protein necessary for the initiation of human TNF-alpha transcription other than, or in addition to, NF-kappa B. PMID- 7890421 TI - Characterization of Pseudomonas aeruginosa-induced MDCK cell injury: glycosylation-defective host cells are resistant to bacterial killing. AB - As a model for bacterium-induced epithelial cell injury, we have studied the interaction of Pseudomonas aeruginosa with polarized Madin-Darby canine kidney (MDCK) cells grown on filters. Following an initial period of bacterial adhesion, foci of injured host cells, which consisted of a central region of cell debris, surrounded by cells that were permeable and apparently necrotic, were formed. Host cell death was quantified by measuring the increased permeability of the monolayer to the macromolecular tracer [14C]inulin. Using this MDCK model system, we have identified bacterial and host cell factors necessary for the host cell damage. The ability of P. aeruginosa to cause MDCK cell damage was independent of elastase or exotoxin A production. In contrast, bacteria with a mutation in the regulatory locus exsA (which are deficient in exoenzyme S production) neither bound to nor caused host cell injury. MDCK cells with defects in cell surface glycosylation were resistant to cell injury, indicating that bacteria may require host cell glycolipids and/or glycoproteins as points of adhesion to cause subsequent host cell injury. PMID- 7890423 TI - Bone marrow nitric oxide production and development of anemia in Trypanosoma brucei-infected mice. AB - Mice infected with Trypanosoma brucei rapidly develop anemia, with the number of circulating erythrocytes reduced by 50% within a week after infection. The present study investigated the relationship between anemia and bone marrow nitric oxide (NO) production. Bone marrow cell populations from T. brucei-infected mice exhibited elevated levels of NO synthase activity which was inhibitable by NG nitro-L-arginine methyl ester. NO production was found to coincide with suppressed bone marrow T-cell proliferation in response to stimulation with the mitogen concanavalin A both in vitro and in vivo. As this indicated that NO may inhibit proliferation in other cell types, particularly hemopoietic precursors, we examined the role of NO in anemia during trypanosome infection. NO production correlated directly with the development of anemia, and treatment of infected mice with NG-nitro-L-arginine methyl ester in vivo to systemically inhibit NO synthesis led to a significant reduction in the anemia. Thus, elevated NO production in the bone marrow of T. brucei-infected mice is likely to play a significant role in the anemia resulting from T. brucei infection. PMID- 7890422 TI - Characterization of a two-gene locus from Bartonella bacilliformis associated with the ability to invade human erythrocytes. AB - Bartonella bacilliformis, the agent of human Oroya fever, invades erythrocytes and causes a severe hemolytic anemia. The ability of two minimally invasive strains of Escherichia coli (DH5 alpha and HB101) to invade human erythrocytes was enhanced 6- to 39-fold by transformation with pIAL1, a plasmid containing a 1,469-bp BamHI fragment from the B. bacilliformis chromosome. Invasiveness was confirmed by gentamicin protection and transmission electron microscopy. DNA hybridization analysis confirmed the presence of the locus in B. bacilliformis KC583 and KC584 and its absence in E. coli chromosomal DNA. Sequencing of the DNA insert of pIAL1 revealed tandem open reading frames of 510 and 558 bp, designated ialA and ialB, respectively. Invasion assays with E. coli containing only an ialA or ialB recombinant suggest that both genes are necessary for invasiveness. The ialA gene is predicted to code for a polypeptide of 170 amino acids (20.1 kDa), and ialB is predicted to code for a polypeptide of 186 amino acids (19.9 kDa). In vitro transcription and translation of pIAL1 produced insert-specific protein bands with masses of approximately 21 and 20 kDa when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Expression of ialA and ialB in E. coli maxicells produced proteins with masses of approximately 21 kDa (IalA) and 18 kDa (IalB). Maxicell and computer analyses suggest that IalB contains an N terminal secretory signal sequence which is posttranslationally cleaved. Searches of various DNA and protein databases revealed that IalA contains an N-terminal region of 35 amino acids with a high degree of homology to an NTPase consensus domain. There is 63.6% sequence conservation between the IalB protein and the invasion-associated protein Ail of Yersinia enterocolitica. PMID- 7890424 TI - Borrelia burgdorferi mutant lacking Osp: biological and immunological characterization. AB - All Borrelia burgdorferi sensu lato isolates characterized to date have one or a combination of several major outer surface proteins (Osps). Mutants of B. burgdorferi lacking Osps were selected with polyclonal or monoclonal antibodies at a frequency of 10(-6) to 10(-5). One mutant that lacked OspA, -B, -C, and -D was further characterized. It was distinguished from the OspA+B+ cells by its (i) autoaggregation and slower growth rate, (ii) decreased plating efficiency on solid medium, (iii) serum and complement sensitivity, and (iv) diminished capacity to adhere to human umbilical vein endothelial cells. The Osp-less mutant was unable to evoke a detectable immune response after intradermal live cell immunization even though mutant survived in mouse skin for the same duration as wild-type cells. Polyclonal mouse serum raised against Osp-less cells inhibited growth of the mutant but not of wild-type cells, an indication that other antigens are present on the surface of the Osp-less mutant. Two types of monoclonal antibodies (MAbs) with growth-inhibiting properties for mutant cells were identified. The first type bound to a 13-kDa surface protein of B. burgdorferi sensu stricto and of B. afzelii. The MIC of the Fab fragment of one MAb of this type was 0.2 micrograms/ml. The second type of MAb to the Osp-less mutant did not bind to B. burgdorferi components by Western blotting (immunoblotting) but did not bind to unfixed, viable cells in immunofluorescence and growth inhibition assays. These studies revealed possible functions Osp proteins in borrelias, specifically serum resistance, and indicated that in the absence of Osp proteins, other antigens are expressed or become accessible at the cell surface. PMID- 7890425 TI - Cytokine mRNA profiles in mononuclear cells in acute aseptic meningoencephalitis. AB - Cytokines are important modulators of inflammation and immune responses. Using in situ hybridization with radiolabelled cDNA oligonucleotide probes, we studied the expression of mRNA encoding the cytokines gamma interferon (IFN-gamma), interleukin 4 (IL-4), IL-6, IL-10, transforming growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), lymphotoxin, and perforin in mononuclear cells (MNC) from blood and cerebrospinal fluid (CSF) of patients with acute aseptic meningoencephalitis (AM) and from blood of healthy controls. Patients in the acute phase of AM had elevated numbers of IFN-gamma mRNA-expressing cells in the blood compared with that of controls and higher numbers of IFN-gamma mRNA expressing cells in their CSF compared with that of convalescent-phase patients, which is in accordance with the antiviral effects of this cytokine. Upregulation of IL-4, IL-6, and IL-10 was found in convalescent-phase patients, which is consistent with the longstanding B-cell response found in AM. TGF-beta and perforin were upregulated in both stages of AM, while the numbers of blood and CSF MNC expressing cytokine mRNA of the TNF family (TNF-alpha and lymphotoxin) did not differ between patients with AM and controls. An even higher elevation in CSF was noticed for MNC expressing most of the cytokines, particularly IL-4 and TGF-beta, reflecting the autonomy of the immune response in the CSF. The definition of cytokine profiles in AM, a self-limiting and benign disease, provides a foundation for future comparisons with other infectious and inflammatory nervous system diseases. PMID- 7890426 TI - Role of the Entamoeba histolytica cysteine proteinase in amebic liver abscess formation in severe combined immunodeficient mice. AB - Evidence from in vitro studies suggest that the Entamoeba histolytica cysteine proteinase plays a role in the tissue lysis and cytopathic effects seen in invasive amebiasis. We used affinity-purified antibodies against a recombinant E. histolytica cysteine proteinase to demonstrate that the proteinase is present extracellularly in amebic liver abscesses in mice with severe combined immunodeficiency (SCID mice). Treatment of E. histolytica trophozoites with specific cysteine proteinase inhibitor E-64 blocked or greatly reduced liver abscess formation at 48 h in SCID mice. Our study suggests an important role for a functional cysteine proteinase in amebic liver abscess formation. PMID- 7890427 TI - Possible receptor for exfoliative toxins produced by Staphylococcus hyicus and Staphylococcus aureus. AB - Exfoliative toxin produced by Staphylococcus hyicus bound to the GM4-like glycolipid extracted from the skin of 1-day-old chickens but did not bind to glycolipid from adult chickens or suckling mice. Exfoliative toxin produced by Staphylococcus aureus bound to the GM4-like glycolipid extracted from the skin of suckling mice but not to glycolipid from 1-day-old or adult chickens. S. hyicus and S. aureus exfoliative toxins lost their toxicity by preincubation with GM4 like glycolipid from 1-day-old chickens and suckling mice, respectively. PMID- 7890428 TI - Colony-stimulating factor 1 in the human response to neonatal listeriosis. AB - Immunity to Listeria monocytogenes, an important pathogen in human neonatal sepsis, is mediated by mononuclear phagocytes, which are regulated by the hematopoietic growth factor colony-stimulating factor 1. Neonates with listeriosis had higher circulating colony-stimulating factor 1 levels and subsequent monocyte counts than those of both noninfected newborns and newborns infected with nonlisterial organisms. PMID- 7890429 TI - Isolation and identification of a glutathione peroxidase homolog gene, gpxA, present in Neisseria meningitidis but absent in Neisseria gonorrhoeae. AB - Antioxidant enzymes are thought to be important for the survival of pathogenic Neisseria species. We isolated a glutathione peroxidase-related gene (gpxA) from Neisseria meningitidis FAM20. The N. meningitidis glutathione peroxidase homolog was 49 to 57% identical to seven other glutathione peroxidase family members over a 49-amino-acid region which is conserved among various species. The gpxA sequence was present in all 7 meningococcal strains tested but absent in 10 gonococcal strains and 6 nonpathogenic neisserial strains as determined by Southern hybridization. The homology of gpxA to mammalian glutathione peroxidases and the presence of this gene specifically in the meningococcus suggest that it is important in the cellular metabolism or defense processes particular to this pathogen. PMID- 7890430 TI - Paracoccidioides brasiliensis-stimulated human gamma/delta T cells support antibody production by B cells. AB - Paracoccidioidomycosis patients show hyperactive humoral immune responses. Consequently, we investigated whether cytokines in supernatants from Paracoccidioides brasiliensis-stimulated gamma/delta T cells support B-cell activation. We detected proliferation of B cells and increased immunoglobulin M (IgM) and IgG production. Thus, gamma/delta T cells may participate in polyclonal B-cell activation during paracoccidioidomycosis. PMID- 7890432 TI - IgA nephropathy: common nephritis leading to end-stage renal failure. AB - IgA nephropathy (IgAN) characterized by mesangial proliferative glomerulonephritis with predominant mesangial IgA deposition is the commonest glomerulonephritis worldwide. In contrast to the initial report indicated a favorable prognosis, subsequent reports have shown a highly variable outcome leading to end-stage renal failure (ESRF) in a significant proportion of patients. Many centers report a high incidence (ranging from 10-22%) of patients with idiopathic IgAN amongst the total population of patients on maintenance dialysis. Most of these patients develop ESRF at their middle-age and hence, will pose a significant and important workload in the dialysis and transplantation programme. Because IgAN is a disease with a variable rate of progression leading to chronic renal failure amongst younger patients and with neither effective nor specific treatment, identification of the clinical and pathologic prognostic indicators for these patients is of paramount importance in planning the long term renal replacement program. PMID- 7890431 TI - Oral vaccination with an attenuated Salmonella typhimurium strain expressing Borrelia burgdorferi OspA prevents murine Lyme borreliosis. AB - Borrelia burgdorferi is the causative agent of Lyme disease. In the mouse model, protection is correlated with the development of antibodies to a major outer surface protein, OspA. In this study, we expressed OspA in an attenuated strain of Salmonella typhimurium and tested the efficacy of the transformed strain in protecting against disease. We show that mice inoculated by gavage developed high titers of anti-OspA antibodies and were protected against an intradermal challenge with the spirochete. PMID- 7890433 TI - Effects of dietary therapy on post renal transplant hyperlipidemia. A prospective study. AB - Hyperlipidemia often occurs after renal transplantation and may contribute to increased cardiovascular morbidity. The National cholesterol education program guidelines (NCEP) recommend dietary modification as the initial therapeutic intervention. We evaluated the effects of the AHA Step I and Step II diets on the serum total cholesterol (TC) and the triglyceride (TG) levels in nondiabetic renal transplant patients. Both the AHA Step I (TC 296 +/- 7 vs 294 +/- 9 mg/dL, p = ns) and Step II diets (TC 282 +/- 8 vs 292 +/- 16 mg/dL, p = ns) failed to significantly lower the serum total cholesterol and the triglycerides levels. During this dietary intervention, the patients' body weight and serum creatinine level remained stable. Our data suggest that neither the AHA Step 1 nor the Step II diet are effective in significantly lowering elevated serum lipids in nondiabetic renal transplant recipients. PMID- 7890434 TI - The outcome of critically ill elderly patients with severe acute renal failure treated by continuous hemodiafiltration. AB - OBJECTIVES: To study the outcome of critically ill elderly patients with severe acute renal failure managed by continuous hemodiafiltration. DESIGN: Prospective study. SETTING: Intensive Care Unit of tertiary institution PATIENTS: Seventy-two consecutive critically ill patients of 65 years or older admitted to the ICU with severe acute renal failure. Seventy similar control patients of age < 65 years. INTERVENTION: Treatment of all patients with continuous hemodiafiltration. MEASUREMENTS AND MAIN RESULTS: Safety and effectiveness of therapy were assessed. Main outcome measures were duration of oliguria, of ICU stay, and hospital stay for survivors, and survival to ICU discharge and to hospital discharge. Mean APACHE II score on admission was 29.8 (95% confidence interval: 28.5 to 31.1) and mean organ failure score prior to initiation of continuous hemodiafiltration was 3.9 (95% confidence interval: 3.6 to 4.2). Sepsis was present in 51 cases (70.8%) and bacteremia or fungemia in 24 (33.3%). Fifty-three (73.6%) required mechanical ventilation for > 3 days. Vasopressor drugs were used in 65 (90.2%). Continuous hemodiafiltration controlled azotemia in all patients and was only associated with minor complications. Thirty-four patients (47.2%) survived to ICU discharge and 30 (41.6%) to hospital discharge. Among survivors, duration of oliguria was 11.6 days (95% confidence interval: 9.1 to 14.1), mean duration of ICU stay 8.6 days (95% confidence interval: 6.1 to 11.) and mean duration of hospital stay 33.1 days (95% confidence interval: 28.8 to 37.4). No statistically significant difference in survival was found when these patients were compared to a control group of similar but younger patients who also received ICU care and continuous hemodiafiltration for the treatment of severe acute renal failure. CONCLUSIONS: A greater than 40% survival was achieved in critically ill elderly patients with severe acute renal failure by the use of continuous hemodiafiltration. These patients had an in hospital survival comparable to that of younger patients. These findings support an aggressive renal replacement approach in such patients and suggest that continuous hemodiafiltration may be ideally suited to their management. PMID- 7890435 TI - Well being in patients on CAPD and hemodialysis. AB - In the present multicenter study, 120 pts who had been treated by both hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) for at least 6 months each, were invited to answer questions on 34 matters, to compare symptoms and their well-being while on the two treatments. Patients were invited to choose HD or CAPD and indicate the reasons for their choice. For 28 patients the first treatment was HD and for 92 CAPD. The mean time between the change of therapy and the study was 46 +/- 35 months. Their final choices were found to be strictly related to the present treatment (p < 0.001). The reasons for choice of CAPD were: more free time (21%), more freedom (67%), better well-being (44%), less worry (5%); for HD they were: more free time (53%), better well-being (39%), less worry (13%), no need for a peritoneal catheter and fewer clinical complications (19%). The catheter was considered more cumbersome than the A.V. fistula, the time involved was considered to be shorter on HD by 52 patients and on CAPD by 39, thirst and cramps were considered to be more frequent and severe on CAPD by half of the patients. The prevalence and severity of problems and symptoms and choice of treatment were not related to sex, job, education or age. PMID- 7890436 TI - Production of interleukin 1 receptor antagonist and interleukin 1 during haemodialysis with cellulose membranes. AB - An in vivo cross-over study has investigated plasma and cellular levels of IL-1 (IL-1 alpha IL-1 beta and IL-1Ra) when using Cuprophan (C) and cellulose triacetate (CTA) membranes to assess the roles of complement activation and dialysate endotoxin content in the induction of cytokines during the dialysis procedure. The mean C5a level during Cuprophan dialysis was 29.9 +/- 0.63 ng/ml (Mean +/- SEM), while for the cellulose triacetate dialysis was 3.09 +/- 0.7 ng/ml. The endotoxin content of the dialysate was 0.31 +/- 0.34 EU/ml and 0.68 +/ 1.39 EU/ml. These two factors failed to produce measurable changes in plasma or cellular IL-1 alpha and IL-1 beta levels during treatment. The plasma IL-1Ra levels predialysis were similar to those for normal controls (CTA 769 +/- 156 ng/ml, C739 +/- 93, normal controls 635 +/- 33) with a considerable day to day variation. A membrane independent fall in plasma IL-1Ra at 15 minutes was noted (CTA 420 +/- 92 ng/ml, C 503 +/- 139) with a return to pre-dialysis levels by the end of treatment. Cellular IL-1Ra levels pre-dialysis were similar to the normal group--(CTA 1904 +/- 291 ng/ml, C 1564 +/- 292 and normal control 1971 +/- 368). However, on average, the values when using cellulose triacetate were 655 +/- 623 pg/ml higher than for Cuprophan (p = 0.03). These findings indicate that the measurement of plasma cytokine levels is of limited use in the study of cytokine induction by the haemodialysis procedure and that IL-1Ra may be a better indicator of the host response to cytokine stimuli during treatment. However, a considerable inter-patient and intra-treatment variation is present and further studies are required to elucidate the factors involved. PMID- 7890437 TI - Continuous ambulatory peritoneal dialysis using self-made, ultrafiltration sterilized, L-lactate-based dialysis solution. AB - Continuous ambulatory peritoneal dialysis was successfully carried out in 6 end stage renal failure patients using self-made, ultrafiltration-sterilized dialysis solutions. A Y-set was used to deliver the above solutions to sterile plastic bags. PMID- 7890438 TI - Mechanical ventricular support using pulsatile Abiomed BVS 5000 and centrifugal Biomedicus-pump in postcardiotomy shock. AB - Since we started using ventricular assist devices (VAD) in July 1987 up to August 1993, 63 of 15,650 (0.4%) patients (pts) who underwent open heart surgery were supported postoperatively by VAD at out institution. Forty-three were male and 20 female, mean age 55.5 years. In 49 pts coronary artery bypass grafting (CABG), in 8 pts valve surgery, in 3 pts combined CABG and valve surgery and in 3 pts corrective procedures for congenital heart disease were performed. Perioperative myocardial infarction was the most frequent indication (73%). In 37 of the 63 pts (58.7%) a centrifugal (Biomedicus pump (group A) was used and in 26 pts (41.3%) a pulsatile Abiomed BVS 5000 (group B). Fourteen of 37 pts (38%) in group A were weaned from the VAD and all of them were discharged. Twenty-three pts were unable to be weaned and 19 of these pts died. The remaining 4 pts were transplanted successfully and subsequently 3 died and 1 was discharged. In all, 15 pts (39%) were long-term survivors. Sixteen of 26 pts (62%) in group B were weaned from VAD and 13 (50%) of them were discharged of whom 3 died. Ten patients were unable to be weaned and 7 of these died. The remaining 3 pts were transplanted successfully. In all, 16 pts (61.5%) were long-term survivors. The shorter the interval between beginning resuscitation and application of VAD the better the outcome. Younger age, VAD installation in OR, support time between 2 and 7 days and Abiomed pump, influence the survival rate positively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7890439 TI - Polymeric biomaterials: influence of phosphorylcholine polar groups on protein adsorption and complement activation. AB - The introduction to polymeric biomaterials of phosphorylcholine polar groups represents an approach towards the development of materials with improved blood compatibility. In this respect, two biomaterials, one a copolymer of butyl methacrylate and 2-methacryloyloxyethylphosphorylcholine (MPC), (poly(BMA-co-MPC) and the other, MPC-grafted Cuprophan, were examined with respect to their influence on protein adsorption and complement activation. Protein adsorption was studied by measurement of the adsorption of radiolabelled single proteins (albumin and fibrinogen), while complement activation was measured using radioimmunoassay for C3a des Arg. The investigation demonstrated that the polymers containing phosphorylcholine polar groups can achieve a marked reduction in protein adsorption and complement activation and supports the utilization of phosphorylcholine polar groups as a means of improving the compatibility of biomaterials for blood-contacting applications. PMID- 7890440 TI - Blood clotting activation and the effect of dilution during plateletpheresis. PMID- 7890442 TI - The self as mediator in the psychopathology of female children of alcoholics. AB - Theoreticians long have argued for the centrality of strength or poverty of self definitions in the prediction and understanding of psychopathology. In this research an empirical measure of strength of self-definition was developed based on the work of Hazel Markus. Consistency of self-description and resistance to challenge for this self-description were found to be related to reported alcoholism, trust, and life satisfaction/depression in children of alcoholics. In fact, nearly all variance in life satisfaction and alcoholism differentiating children of alcoholics (COA) from non-COA groups was controlled by the self variables. Clinical and theoretical implications of the significant findings were discussed. PMID- 7890441 TI - Sociocultural and psychological factors in American Indian drug use: implications for treatment. AB - Use of alcohol and other drugs has been acknowledged as a serious problem among American Indian populations. This study was designed to 1) compare female and male American Indian substance users in residential treatment on psychological (self-esteem, depression, attributional style) and sociocultural (demographics, personal drug use history, family history, acculturation) variables, and 2) examine relationships of the psychological and sociocultural variables with program completion. Results showed that females experienced more family dysfunction (family members misuse of substances, and emotional, physical, and sexual abuse) than males. Both females and males showed positive change on the psychological measures from treatment entry to treatment completion. The factors predicting dropout before program completion were divorce, use of cocaine and depressants, and living in foster care as a child. Implications for prevention, intervention, and training of treatment service providers are discussed. PMID- 7890443 TI - Problems of accuracy in official statistics on drug-related deaths. AB - The accuracy of statistics on drug-related deaths depends on numerous processes at work from the investigation of the death-scene to the categorization of the case in official statistics. This article discusses problems in lack of information, pressures on medical examiners, definition, nomenclature, and conventions of coding. The implications for comparisons of rates of drug-related deaths across ethnic groups and geographic areas are discussed. PMID- 7890444 TI - Cocaine selling among urban black and white adolescent males. AB - Data from a longitudinal study of juvenile detainees are used to examine the relationships between cocaine selling, substance use, and other delinquency among the Black and White males in the study. A descriptive comparison of rates of cocaine selling among the youths is followed by a descriptive comparison of prevalence of substance use and other delinquency across four subgroups: White and Black males indicating they sold and did not sell cocaine. These comparisons are followed by analyses of variance examining the relationships between involvement in substance use and other delinquency, and ethnicity, cocaine selling, and the interaction of ethnicity and cocaine selling. Important ethnicity and cocaine-selling effects are found, but not ethnicity by cocaine selling interactions. The implications of our findings for theory and service provision are drawn. PMID- 7890445 TI - Perceiving need for drug treatment: a look at eight hypotheses. AB - Data from the Drug Use Forecasting Program, sponsored by the National Institute of Justice, were used to examine eight hypotheses predicting the perceived need for drug treatment among drug-using arrestees. The findings support five of the eight hypotheses, including those related to drug severity, drug type, prior treatment experience, ethnicity, and the fear of AIDS. There was no support for the gender-related help-seeking or the social isolation hypotheses, and the findings contradict the maturing out hypothesis. The policy implications of our findings are discussed. PMID- 7890446 TI - Substance use intervention failure: a point of view or how the cure becomes the disease or an ode to experts on incurability or masking the disease, mitigating someone's pain but providing no basic cure/solution. AB - Substance use intervention, both in the private and public sectors, continues to be associated with failure. This paper makes the assumption that: 1) there is a need to systematically consider and explore FAILURE in its various parameters (definitions, characteristics, forms, shapes, potencies, densities, directions, tempos, levels, phases, meanings, and adhesiveness), sources, and "demands" in the broad area of substance use intervention; 2) we can learn from failure (categorizing its processes and outcomes, selecting foci for intervention, and failure's "veracity," status, transmittability and potential/actual usability over time); and 3) we should continue to repeat this process until there is little need to do so. As times and definitions change, there will never be an end to failure or the need to learn from failure. Failure is considered as a value, and having value, on a multidimensional, dynamic gradient (minimal to maximal), being describable, discernable, catagorizable, understandable, while being culture-site-ideologically bound/influenced. Exploring FAILURE offers us-in our various substance use intervention roles-the opportunity to learn from what we have done and to more appropiately plan, implement, and assess what we may want and/or need to know and to do. Examples are given of ongoing sources of built-in substance use intervention failure. PMID- 7890447 TI - Sharing injecting equipment and sexual behavior in ambulatory intravenous drug users: a national survey (Spain). AB - This article examines the relationship between sharing and sexual behavior in a nationwide sample of 1,074 intravenous drug users (IVDUs) in ambulatory treatment in Spain. Of our sample, 31.9% shared or had shared injecting equipment. Sharing was associated with sex-less frequent in males--and yielded an inverse relationship with age, years of education, and age at first intravenous drug use. Sharers, especially women, engaged more frequently in sex in exchange for money. A small proportion (6.3%) of male IVDUs had bisexual or homosexual relations. Condoms were always used by 18.4% of males and 15.9% of females. The sharing of injecting equipment was not generally associated with a particular type of penetrative sexual encounter, although condom use was less frequent among IVDUs who shared injecting equipment. The limitations of the present study are discussed. PMID- 7890448 TI - Do response options influence self-reports of alcohol use? AB - The influence of response options on self-reported frequency of alcohol use was evaluated in an experimental study of 350 students at a west coast university. Respondents were asked about their frequency of alcohol use in the last 7 days, 30 days, 90 days, and 180 days with three methodological factors randomized: 1) how quantitative the response options were; 2) order of presentation of close ended response options; and 3) relative placement of alcohol use items in the questionnaire. Results indicate that the quantitativeness of response options and the location of items within the questionnaire have minimal effects on the average frequency of alcohol use and number of inconsistent responses over a wide range of time frames. However, presenting higher frequency response options prior to lower frequency response options increased self-reported frequency of having consumed 2 or more drinks in the last 30 days and frequency of alcohol use over the last 180 days. PMID- 7890449 TI - Group psychotherapy on state hospital admission wards. AB - Group psychotherapy with chronically mentally ill patients on psychiatric admission units can be a complex and challenging endeavor. Besides a varied and unmotivated population, numerous other factors that are specific to the admission units of state-supported mental hospitals impinge on the therapeutic process. These factors need to be taken into consideration in conducting group psychotherapy. The current article delineates some of the problems that can affect group therapy in state-supported psychiatric facilities, and some of the techniques that the authors found efficacious in conducting group psychotherapy are discussed. PMID- 7890450 TI - The nequipos' collusion with the patient's family of origin in analytic group psychotherapy. AB - When the analytic group is led by individuals paired for educational reasons, that is, by a supervisor and his or her student, the difficulty in conducting the group becomes magnified. Such teams are called nequipos and it is hypothesized that they will not function optimally until the latter phases of their development. The authors describe the mistakes they made as early phase nequipos in their treatment of one patient in group psychotherapy. PMID- 7890451 TI - "Experience-sharing" as an antidote to dependence-making behavior of general practitioners. AB - This article explores how group-dynamic interventions can be used to teach health professionals to counter impulses to make clients dependent on them. The basic assumption, derived from Kohut's work on narcissism, is that dependence-making behavior is connected with deep-rooted feelings of insufficiency resulting from a defective autonomy. A part of the standard Dutch General Practice (GP) training program, experience-sharing in groups of 12 GP trainees, offers opportunities to explore these feelings. The format of this experience-sharing (well-defined boundaries, minimal structure, facilitating leaders) often evokes behavior in which the peculiarities of the dependence-making behavior of the GP's vis-a-vis patients are mirrored: that is, dependent behavior. In order to analyze and influence this behavior, use can be made of Levine's model of group psychotherapy, which focuses on enhancing autonomy. In this paper we show, by means of four group cases, how Levine's framework can be used to enhance autonomy, lessen dependence, and thus diminish the tendency of GP's toward dependence-making behavior. PMID- 7890452 TI - On the group entity. AB - The group entity is postulated as a construct that accounts for phenomena, which, in a group, come to be experienced by group members as "the group" and that are referred to in the literature as the group-as-a-whole. This article reviews the literature on whole group phenomena. It describes the group entity as it is formed and maintained. A process is outlined using the ideas of spatialization, objectization, enlivenment, and participation. These concepts will describe the way in which the group entity arises and comes to be a part of the individual's experience in a group. Projective identification is viewed as the main mechanism responsible for the intragroup dynamics involving the group entity. PMID- 7890453 TI - Indirect scapegoating via projective identification and the mother group. AB - This article proposes an indirect route to role suction and scapegoating via projective identification (PI) of members' split-off feelings into the group. For these members, the group is a good, soothing mother. Other members, sensitive to a projected feeling, introject it from the group and may become scapegoats. For them the group is the bad, invasive mother. This model provides a unifying explanation for the literature's contrasting depiction of the group as either a good or a bad mother. By fostering the containment and holding functions of the group and exploring and interpreting the interrelated phenomena of PI, the mother group, and indirect scapegoating, the therapist can facilitate the development of more realistic, integrated, internal-object-relations, which in turn fosters improved interpersonal relations. PMID- 7890454 TI - Block training in group analysis: the Norwegian program. AB - Block training in group psychotherapy makes it possible to train professionals living far apart and to import conductors to an area or country lacking sufficient expertise. This article reports experience with such a training program in Norway. Training is given in blocks of 5 weekends a year, each weekend containing small group therapy, supervision, theory courses, lectures, and large group experiences. The participants were questioned about their personal and professional gains from the training. These findings and the effect of the program in relation to stated goals are discussed. PMID- 7890455 TI - Countertransference issues in group psychotherapy with HIV-positive and AIDS patients. AB - Mental health professionals are increasingly aware of the special difficulties encountered by therapists working with HIV-positive and AIDS patients. In this report, countertransference issues experienced by therapists leading a psychotherapy group for heterosexual, drug-using HIV-positive and AIDS patients in an inner city hospital are explored. Countertransference is discussed under the headings of helplessness, death anxiety, and anger. PMID- 7890456 TI - Early leg blood flow adjustment during dynamic foot plantarflexions in upright and supine body position. AB - The time courses of leg blood flow, systolic peak velocity, heart rate and blood pressure have been studied in nine health volunteers during dynamic exercise in upright sitting and in a tilted sitting body position. In both positions the subjects performed single and repeated foot plantarflexions against light and moderate forces corresponding to 5%-10% and 25%-30% of maximal voluntary contraction. The following measurement techniques were used: Doppler ultrasound method (blood flow parameters), FINAPRES device (arterial blood pressure) and standard ECG chest leads (heart rate). At rest the supine blood flow parameters measured in the arteria femoralis were significantly higher than in the upright sitting position. In both positions, even one single plantarflexion at the light exercise intensity caused significant increases in blood flow for almost 20s. The major part of the blood flow response to repeated contractions always occurred within the first 10s at virtually unchanged blood pressures. During this initial phase upright leg blood flow increased by factors of 2.5 (light exercise) and 3.1 (moderate exercise). The corresponding values in the tilted sitting posture were 1.7 and 1.9, respectively. The initial increases in the upright position were too large to be attributed only to the increase of the perfusion pressure caused by the withdrawal of the hydrostatic pressure on the venous side ("muscle pump"). Additional, fast decreases in local resistance have to be considered. In the supine posture effects on local resistance have to be taken into account for the early increases in blood flow since hydrostatic effects on arterio-venous pressure differences are too small. The present findings indicate that the effects of repeated contraction-relaxation cycles on the early adjustment of muscle blood flow are not sufficiently described by a "muscle pump" that induces only venous volume shifts and hydrostatic pressure changes. Additional fast effects on local resistance have to be taken into account. PMID- 7890457 TI - Relative cross-sectional areas of upper and lower extremity muscles and implications for force prediction. AB - The purposes of this investigation were to examine the reduction in variability when muscle size is expressed relative to a functional group and its effect on improving muscle force prediction. Fourteen subjects performed maximum voluntary contractions (MVC) of elbow flexion and knee extension and had CT scans taken of the thigh and upper arm. The variation of relative cross-sectional area (RCSA) was significantly lower than CSA (p < 0.01). No significant differences were found between male and female RCSAs. A method of predicting individual muscle forces based on an MVC and RCSA is presented that reduced prediction errors to a third of those predicted on the basis of CSA and a specific tension or stress value of muscle. PMID- 7890458 TI - Ventilation parallels plasma potassium during incremental and continuous variable intensity exercise. AB - The aim of the present investigation was to examine the relationship between plasma potassium (K+) and ventilation (VE) during incremental and prolonged continuous exercise which varied between low and moderate intensity. Seven well trained male cyclists who had a mean maximal aerobic power (VO2max) of 69.4 +/- 2.9 ml/kg/min were recruited to participate as subjects. The graded incremental exercise bout was composed of 3 min stages set to elicit 40, 50, 60, 70, 80 and 90% VO2max. The continuous variable intensity exercise consisted of 30 min of cycling at 45% VO2max and then 6 x 16 min periods which consisted of cycling for 8 min at 75% VO2max and 8 min at 45% VO2max. During prolonged continuous exercise, VE and plasma K+ changed in a coordinated manner between the low and moderate intensity exercise bouts with the responses during the moderate intensity intervals being significantly greater (p < 0.05) than the responses during the low intensity intervals. During the incremental exercise test, a strong positive relationship between VE and plasma K+ concentration was found for each subject. However, a positive relationship and slope was also found when the VE/K+ ratio was correlated with exercise intensity (r = 0.90-0.99). This indicates that with increasing exercise intensity, the rise in VE becomes increasingly greater than the rise in plasma K+. These findings suggest that the plasma K+ concentration contributes to but may not be the sole determinant of ventilatory regulation during exercise. PMID- 7890459 TI - Hormonal and metabolite responses to glucose and maltodextrin ingestion with or without the addition of guar gum. AB - The purpose of this study was to examine the effects of ingesting water (P), a glucose solution (GL), a maltodextrin solution (Md), a glucose solution with 8% guar gum (GL+G), and a maltodextrin solution with 8% guar gum (Md+G), on the hormonal and metabolite responses during cycling, and on subsequent time to exhaustion. Five male subjects undertook five 90 min rides on a bicycle ergometer at an exercise intensity corresponding to 65% VO2max after having ingested 1 g.kg 1 body weight of the test product in 400 ml of water immediately before the exercise. Blood samples were taken during the trials for analyses of adrenaline, noradrenaline, insulin, glucagon, glucose, lactate and non-esterified fatty acids (NEFA). Respiratory measures were also undertaken during the trials for the determination of oxygen consumption (VO2) and respiratory exchange ratio (RER), from which the carbohydrate oxidation rates were calculated. Rates of perceived exertion (RPE) were also assessed. Ten minutes after the 90 min ride, subjects exercised to volitional exhaustion at an exercise intensity of 75% VO2max. ANOVA revealed that there were significant differences between the treatments for adrenaline (p < 0.01), insulin (p < 0.05), glucose (p < 0.01), lactate (p < 0.01), NEFA (p < 0.01), RER (p < 0.001) and carbohydrate oxidation rate (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7890460 TI - The effects of two different periods of weight-reduction on selected performance parameters in elite lightweight oarswomen. AB - Six successful members of the British Women's Lightweight Rowing Team were assessed before and after two-month (1990) and four-month (1991) periods of weight-reduction controlled by reduced caloric intake, while engaged in their normal physical training. Fat free mass (FFM) was calculated from body weight (BW) by utilising total body potassium measurements. Maximal oxygen intake (VO2max), respiratory anaerobic threshold (Tvent), upper body anaerobic peak power (PP) and mean power (MP) outputs, and knee flexor (KF) and extensor (KE) isokinetic peak torques were among the physiological parameters assessed. No statistical differences were noted between the data obtained prior to the two weight-reduction periods, and both periods resulted in lower BW (p < 0.001) and FFM (p < 0.05); approximately 50% of the lost BW was FFM. At the end of the two month weight-reduction period Tvent (p < 0.02) and KF (p < 0.02) decreased. In contrast, a similar BW loss during the four-month period was associated with higher VO2max (p < 0.01) and PP (p < 0.05) compared with values prior to weight reduction. Comparisons between the percentage changes pre to post BW loss showed that the longer weight-reduction period was associated with significantly improved VO2max (p < 0.01), Tvent (p < 0.005), PP (p < 0.05) and KF (p < 0.05). We conclude: a) the proportion (50%) of weight lost as FFM in the present elite rowers is higher than the suggested optimal figure of 22%, and b) compared to four months, 6-7% of BW loss over two months may adversely influence fitness related parameters in international lightweight oarswomen. PMID- 7890461 TI - Effects of moderate energy restriction on physical performance and substrate utilization in non-obese men. AB - Energy restriction (ER) has shown to be an effective 'anti-aging' factor in rodents, resulting in an increased life span and preventing or delaying the occurrence of many age-related diseases in rodents. As a part of a feasibility study on the potential application of ER in humans, we studied the effects of moderate ER on physical performance in 24 apparently healthy, non-obese middle aged men. After two weeks of weight maintenance the ER group (n = 16) received 80% of their habitual energy intake, while a control group (n = 8) still received their weight-maintaining diet for ten weeks. Physical performance (bicycle ergometer) was estimated by a maximal (until exhaustion) and a submaximal (30 min at 60% of VO2max) exercise test. After the experimental period the subjects in ER group had a significantly shorter cycling time (delta = 1.31 +/- 1.14 vs -0.45 +/ 1.56 min, p = 0.01), and thus had a lower maximal power output (delta = 4.3 +/- 5.9 vs -6.3 +/- 13.6 watt, p < 0.05) and maximal oxygen uptake (delta = 0.03 +/- 0.18 vs -0.18 +/- 0.321/min, p = 0.05) during the maximal exercise test, than the subjects in the control group. None of these changes correlated with weight loss. As in every exercise test, motivation could have played an important role. During the submaximal exercise test no significant changes between the two groups in HR, VO2, RER and FFA, glucose, lactate and catecholamine levels were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 7890462 TI - Effects of interval training and a taper on cycling performance and isokinetic leg strength. AB - The purpose of this study was to determine whether changes in isokinetic leg strength parallel changes in cycling performance during a six-week high-intensity aerobic interval training program and a subsequent two-week taper. Eleven male collegiate cyclists participated in one competitive cycling graded exercise test, four consecutive days of aerobic intervals (30 min @82.2 +/- 0.74% HRmax, 1:1 work:relief), and four continuous rides (1-2 hr @65-80% HRmax) weekly. Pedalling cadence during training was generally 70-80 rpm suggesting a knee joint velocity of approximately 210 degrees.sec-1. Cycling performance and peak isokinetic torque (TQpk) for knee flexors (HAM) and knee extensors (QUAD) @30, 120, 210, and 300 degrees.sec-1 were assessed before, every two weeks during, and each week for two weeks following six weeks of interval training. Performance increased significantly during training (15%) and increased further during the taper (8%). QUAD TQpk @30 and 120 degrees.sec-1 increased significantly during training and the taper. In contrast, QUAD TQpk @210 and 300 degrees.sec-1 and HAM TQpk for all velocities were not significantly elevated following training. Interestingly, QUAD TQpk @300 but not 210 degrees.sec-1 significantly increased during the taper. Data from this study demonstrates that high-intensity aerobic interval cycling can promote gains in QUAD strength which occur primarily at contraction velocities slower than those utilized during cycling training. Additionally, a two-week taper can produce significant improvements in cycling performance (8%) and QUAD strength (8-9%) at 30 and 120 degrees.sec-1, however, the time-courses for these improvements do not parallel one another. PMID- 7890463 TI - The effects of tapering on strength performance in trained athletes. AB - The optimum pre-competition taper procedure for "strength athletes" is not known. We examined voluntary strength and evoked contractile properties of the elbow flexors over a 10 day rest only (ROT) and a 10 day reduced volume taper (RVT) in 8 resistance trained males (23 +/- 2.1 years). Following 3 wks of standardized training of the elbow flexors, subjects were randomly assigned to one of the tapers. Upon completion, they resumed training for 3 wks and completed the other taper. No arm training was performed during the ROT, while high intensity, low volume training was done every second day during the RVT. Maximum isometric (MVC), low (0.52 rad.s-1; LV) and high velocity (3.14 rad.s-1; HV) concentric peak torque, and evoked isometric twitch contractile properties were measured before and after each training phase and every 48 h during each taper. ANOVA comparison of the tapers revealed that MVC increased (p < or = 0.05) over pre taper values throughout the RVT (measurement days 2, 4, 6, 8 and 10), as did LV at 2, 4, 6, and 8 d. MVC did not change over the ROT but LV was significantly higher on day 2 and lower on days 8 and 10. LV was also greater on days 4, 6, 8 and 10 during the RVT compared to the ROT. The evoked contractile properties remained largely unchanged. The data indicate that resistance-trained athletes can improve low velocity concentric strength for at least 8 days by greatly reducing training volume, but maintaining training intensity. PMID- 7890464 TI - Comparison of a simulated 16.1-km time trial, VO2max and related factors in cyclists with different ventilatory thresholds. AB - Differences in cycling performance have been observed in cyclists with similar VO2max values yet different lactate thresholds. The purpose of the current study was to compare a simulated 16.1-km cycling time trial, VO2max and related factors in cyclists who significantly varied in ventilatory threshold. From an original group of 18 category III or IV cyclists, two groups of 6 cyclists were formed based on ventilatory threshold values as high (77 +/- 4% of VO2max-Group H) or low (68 +/- 2.8% - Group L). VO2max and a 16.1-km time trial were completed on a Velodyne trainer. No significant difference (p > or = 0.05) was noted between groups in VO2max (Group H 4.00 +/- 0.281.min-1, Group L 4.15 +/- 0.671.min-1), however significant differences (p < or = 0.05) were found in ventilatory threshold and time trial scores. Group H completed the time trial in 16.29 +/- 2.08 min while Group L averaged 20.93 +/- 3.03 min. Group H completed the time trial 28% more quickly by working at a significantly higher percentage of VO2max, a higher power output and a faster pedal rate than Group L. From a battery of physiologic and body composition parameters, the ventilatory threshold expressed as VO2 (l.min-1) was the best predictor (r = -0.76) of time trial performance in the 12 cyclists. The findings of this study indicate that the ventilatory threshold was superior to VO2max in discerning performance differences in a 16.1 km cycling time trial, and was the best predictor of the simulated time trial performance. PMID- 7890465 TI - Peak running velocity is highly related to distance running performance. AB - This study examined the relationship between the peak running velocity (PRV) obtained during a horizontal, incremental treadmill test and distance running performance in a group of highly-trained male (N = 14) and female (N = 9) distance runners. Performance (5 km run time) was assessed with a self-paced time trial under laboratory conditions in an attempt to minimize extraneous variables which could affect performance (i.e. environmental conditions, terrain, etc.); relationships with recent best 5 km race time were also determined. PRV was highly related to 5 km performance whether determined from the time trial (r2 = 0.94, p < 0.001) or recent race (r2 = 0.89, p < 0.001). A new finding was that PRV was similarly related to performance in both the male (r2 = 0.83, p < 0.001) and female (r2 = 0.80, p < 0.001) athletes. Peak running velocity is thus highly predictive of distance running performance in highly-trained endurance runners. This finding has important practical implications, as PRV can be measured without extensive metabolic equipment and/or invasive techniques. PMID- 7890466 TI - EMG profiles of ACL-deficient patients during walking: the influence of mild fatigue. AB - The purpose of this study was to determine muscle activities after ACL rupture during walking and running and to investigate the influence of mild fatigue (10 min walking) on these activities. A group of 12 patients with ACL-ruptures was compared with a control group (healthy volunteers) of 15 persons. Linear envelopes of EMG-activity from vastus medialis, vastus lateralis, biceps femoris and medial hamstrings were measured. Patients and control persons walked on a treadmill at speeds of 1.2 m/s (samples at t = 2 min and t = 12 min) and 2.8 m/s i.e. running (sample at t = 15 min). The patient group showed significantly lower muscle activities of vastus lateralis (p < 0.001) and medial hamstrings (p < 0.05) for both the injured and uninjured leg during running compared to the control group. After 10 minutes walking, the mean-EMG of biceps femoris (p < 0.05) and medial hamstrings (p < 0.01) decreased as did the activity time of biceps femoris (p < 0.05), medial hamstrings (p < 0.01) and vastus medialis (p < 0.001) for the injured leg of the patient group. Control persons showed no significant changes. Thus, mild fatigue did effect only the EMG-pattern of the patients. Patients with ACL-ruptures should be trained not only on strength and stabilisation, but also on endurance. A decrease in hamstrings activity during walking might be a sensitive measure for evaluation of the rehabilitation process, as those muscles may be able to substitute ACL-deficiency. PMID- 7890467 TI - Clinical manifestations of the 'athlete's heart' in prepubertal male runners. AB - Cardiac findings in adult endurance athletes are well characterized, but data regarding the "athlete's heart" in children are limited. This study evaluated cardiovascular features of 10 male prepubertal distance runners ages 11-13 years compared to 18 physically active but untrained boys. Mean VO2max values on treadmill testing for the two groups were 61.2 (3.2) and 51.1 (4.3) ml.kg-1.min 1, respectively. No significant differences in the frequency of carotid bruits, cervical venous hums, heart murmurs, or third and fourth heart sounds were observed between the groups. Mean resting heart rate was 71 (9) bpm for the runners and 73 (8) for the controls (p > 0.05). No significant differences were seen in EKG intervals, axes, or precordial voltages between runners and controls, and echocardiographic chamber sizes, wall thicknesses, and mass indexed to body surface area were also similar (p > 0.05). This study failed to identify clinical features of the "athlete's heart" in competitive child endurance runners compared to non-trained subjects. PMID- 7890469 TI - Transcutaneous pCO2-monitoring during exercise is valid! PMID- 7890468 TI - Effects of cast-bracing of the knee on physical performance in healthy subjects. AB - Effects of application of a hinged cast-brace on thigh muscle strength and physical performance tests were studied in eight healthy volunteers. The cast brace was applied to one leg for four weeks. The subjects were free to move around. The extra loading by the cast-brace was determined in a progressive uphill walk test on a treadmill with measurements of oxygen uptake, heart rate and plasma lactate concentration. Submaximal oxygen uptake in the uphill walk test was raised significantly (average 9%) on the day after application. After four weeks of cast-brace wearing the submaximal oxygen uptake in the uphill walk test had decreased, but remained elevated (average 4%) even one day after removal. Heart rate was significantly higher (average 7%) during cast application and after removal. Plasma lactate concentration, however, was not influenced. To investigate the effect of four weeks cast-bracing various performance tests to judge the thigh muscle function were taken before application and after removal. No significant changes in peak torque of knee flexion and extension, in physiologic variables at submaximal running pace during treadmill exercise, maximal running speed, 60 m dash, or in jump height were found. In conclusion, cast-bracing of a healthy knee for four weeks has no significant effects on physical performance after removal. PMID- 7890470 TI - Is expert psychiatric testimony fundamentally immoral? PMID- 7890472 TI - Case-mix funding and legislated psychiatric care. PMID- 7890471 TI - Gender and the assessment of dangerousness in the psychiatric emergency room. PMID- 7890473 TI - The role of mental health practitioners' testimony in the Israeli Supreme Court. PMID- 7890474 TI - Personality disorders and criminal responsibility: a second opinion. PMID- 7890475 TI - Junior psychiatrists and emergency compulsory detention in Scotland. PMID- 7890476 TI - Social and cognitive processing deficits in violent offenders: implications for treatment.